Novel proteins and nucleic acids encoding same

Abstract

The present invention provides novel isolated polynucleotides and small molecule target polypeptides encoded by the polynucleotides. Antibodies that immunospecifically bind to a novel small molecule target polypeptide or any derivative, variant, mutant or fragment of that polypeptide, polynucleotide or antibody are disclosed, as are methods in which the small molecule target polypeptide, polynucleotide and antibody are utilized in the detection and treatment of a broad range of pathological states. More specifically, the present invention discloses methods of using recombinantly expressed and/or endogenously expressed proteins in various screening procedures for the purpose of identifying therapeutic antibodies and therapeutic small molecules associated with diseases. The invention further discloses therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of disorders involving any one of these novel human nucleic acids and proteins.

Description

FIELD OF THE INVENTION

[0002] The present invention relates to novel polypeptides that are targets of small molecule drugs and that have properties related to stimulation of biochemical or physiological responses in a cell, a tissue, an organ or an organism. More particularly, the novel polypeptides are gene products of novel genes, or are specified biologically active fragments or derivatives thereof. Methods of use encompass diagnostic and prognostic assay procedures as well as methods of treating diverse pathological conditions.

BACKGROUND

[0003] Eukaryotic cells are characterized by biochemical and physiological processes which under normal conditions are exquisitely balanced to achieve the preservation and propagation of the cells. When such cells are components of multicellular organisms such as vertebrates, or more particularly organisms such as mammals, the regulation of the biochemical and physiological processes involves intricate signaling pathways. Frequently, such signaling pathways involve extracellular signaling proteins, cellular receptors that bind the signaling proteins and signal transducing components located within the cells.

[0004] Signaling proteins may be classified as endocrine effectors, paracrine effectors or autocrine effectors. Endocrine effectors are signaling molecules secreted by a given organ into the circulatory system, which are then transported to a distant target organ or tissue. The target cells include the receptors for the endocrine effector, and when the endocrine effector binds, a signaling cascade is induced. Paracrine effectors involve secreting cells and receptor cells in close proximity to each other, for example two different classes of cells in the same tissue or organ. One class of cells secretes the paracrine effector, which then reaches the second class of cells, for example by diffusion through the extracellular fluid. The second class of cells contains the receptors for the paracrine effector; binding of the effector results in induction of the signaling cascade that elicits the corresponding biochemical or physiological effect. Autocrine effectors are highly analogous to paracrine effectors, except that the same cell type that secretes the autocrine effector also contains the receptor. Thus the autocrine effector binds to receptors on the same cell, or on identical neighboring cells. The binding process then elicits the characteristic biochemical or physiological effect.

[0005] Signaling processes may elicit a variety of effects on cells and tissues including by way of nonlimiting example induction of cell or tissue proliferation, suppression of growth or proliferation, induction of differentiation or maturation of a cell or tissue, and suppression of differentiation or maturation of a cell or tissue.

[0006] Many pathological conditions involve dysregulation of expression of important effector proteins. In certain classes of pathologies the dysregulation is manifested as diminished or suppressed level of synthesis and secretion of protein effectors. In other classes of pathologies the dysregulation is manifested as increased or up-regulated level of synthesis and secretion of protein effectors. In a clinical setting a subject may be suspected of suffering from a condition brought on by altered or mis-regulated levels of a protein effector of interest. Therefore there is a need to assay for the level of the protein effector of interest in a biological sample from such a subject, and to compare the level with that characteristic of a nonpathological condition. There also is a need to provide the protein effector as a product of manufacture. Administration of the effector to a subject in need thereof is useful in treatment of the pathological condition. Accordingly, there is a need for a method of treatment of a pathological condition brought on by a diminished or suppressed levels of the protein effector of interest. In addition, there is a need for a method of treatment of a pathological condition brought on by a increased or up-regulated levels of the protein effector of interest.

[0007] Small molecule targets have been implicated in various disease states or pathologies. These targets may be proteins, and particularly enzymatic proteins, which are acted upon by small molecule drugs for the purpose of altering target function and achieving a desired result. Cellular, animal and clinical studies can be performed to elucidate the genetic contribution to the etiology and pathogenesis of conditions in which small molecule targets are implicated in a variety of physiologic, pharmacologic or native states. These studies utilize the core technologies at CuraGen Corporation to look at differential gene expression, protein-protein interactions, large-scale sequencing of expressed genes and the association of genetic variations such as, but not limited to, single nucleotide polymorphisms (SNPs) or splice variants in and between biological samples from experimental and control groups. The goal of such studies is to identify potential avenues for therapeutic intervention in order to prevent, treat the consequences or cure the conditions.

[0008] In order to treat diseases, pathologies and other abnormal states or conditions in which a mammalian organism has been diagnosed as being, or as being at risk for becoming, other than in a normal state or condition, it is important to identify new therapeutic agents. Such a procedure includes at least the steps of identifying a target component within an affected tissue or organ, and identifying a candidate therapeutic agent that modulates the functional attributes of the target. The target component may be any biological macromolecule implicated in the disease or pathology. Commonly the target is a polypeptide or protein with specific functional attributes. Other classes of macromolecule may be a nucleic acid, a polysaccharide, a lipid such as a complex lipid or a glycolipid; in addition a target may be a sub-cellular structure or extra-cellular structure that is comprised of more than one of these classes of macromolecule. Once such a target has been identified, it may be employed in a screening assay in order to identify favorable candidate therapeutic agents from among a large population of substances or compounds.

[0009] In many cases the objective of such screening assays is to identify small molecule candidates; this is commonly approached by the use of combinatorial methodologies to develop the population of substances to be tested. The implementation of high throughput screening methodologies is advantageous when working with large, combinatorial libraries of compounds.

SUMMARY OF THE INVENTION

[0010] The invention includes nucleic acid sequences and the novel polypeptides they encode. The novel nucleic acids and polypeptides are referred to herein as NOVX, or NOV1, NOV2, NOV3, etc., nucleic acids and polypeptides. These nucleic acids and polypeptides, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as “NOVX” nucleic acid, which represents the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 78, or polypeptide sequences, which represents the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 78.

[0011] In one aspect, the invention provides an isolated polypeptide comprising a mature form of a NOVX amino acid. One example is a variant of a mature form of a NOVX amino acid sequence, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed. The amino acid can be, for example, a NOVX amino acid sequence or a variant of a NOVX amino acid sequence, wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed. The invention also includes fragments of any of these. In another aspect, the invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof.

[0012] Also included in the invention is a NOVX polypeptide that is a naturally occurring allelic variant of a NOVX sequence. In one embodiment, the allelic variant includes an amino acid sequence that is the translation of a nucleic acid sequence differing by a single nucleotide from a NOVX nucleic acid sequence. In another embodiment, the NOVX polypeptide is a variant polypeptide described therein, wherein any amino acid specified in the chosen sequence is changed to provide a conservative substitution. In one embodiment, the invention discloses a method for determining the presence or amount of the NOVX polypeptide in a sample. The method involves the steps of: providing a sample; introducing the sample to an antibody that binds immunospecifically to the polypeptide; and determining the presence or amount of antibody bound to the NOVX polypeptide, thereby determining the presence or amount of the NOVX polypeptide in the sample. In another embodiment, the invention provides a method for determining the presence of or predisposition to a disease associated with altered levels of a NOVX polypeptide in a mammalian subject. This method involves the steps of: measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and comparing the amount of the polypeptide in the sample of the first step to the amount of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, the disease, wherein an alteration in the expression level of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

[0013] In a further embodiment, the invention includes a method of identifying an agent that binds to a NOVX polypeptide. This method involves the steps of: introducing the polypeptide to the agent; and determining whether the agent binds to the polypeptide. In various embodiments, the agent is a cellular receptor or a downstream effector.

[0014] In another aspect, the invention provides a method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions of a NOVX polypeptide. The method involves the steps of: providing a cell expressing the NOVX polypeptide and having a property or function ascribable to the polypeptide; contacting the cell with a composition comprising a candidate substance; and determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition devoid of the substance, the substance is identified as a potential therapeutic agent. In another aspect, the invention describes a method for screening for a modulator of activity or of latency or predisposition to a pathology associated with the NOVX polypeptide. This method involves the following steps: administering a test compound to a test animal at increased risk for a pathology associated with the NOVX polypeptide, wherein the test animal recombinantly expresses the NOVX polypeptide. This method involves the steps of measuring the activity of the NOVX polypeptide in the test animal after administering the compound of step; and comparing the activity of the protein in the test animal with the activity of the NOVX polypeptide in a control animal not administered the polypeptide, wherein a change in the activity of the NOVX polypeptide in the test animal relative to the control animal indicates the test compound is a modulator of latency of, or predisposition to, a pathology associated with the NOVX polypeptide. In one embodiment, the test animal is a recombinant test animal that expresses a test protein transgene or expresses the transgene under the control of a promoter at an increased level relative to a wild-type test animal, and wherein the promoter is not the native gene promoter of the transgene. In another aspect, the invention includes a method for modulating the activity of the NOVX polypeptide, the method comprising introducing a cell sample expressing the NOVX polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide.

[0015] The invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof. In a preferred embodiment, the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring allelic nucleic acid variant. In another embodiment, the nucleic acid encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant. In another embodiment, the nucleic acid molecule differs by a single nucleotide from a NOVX nucleic acid sequence. In one embodiment, the NOVX nucleic acid molecule hybridizes under stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 78, or a complement of the nucleotide sequence. In another aspect, the invention provides a vector or a cell expressing a NOVX nucleotide sequence.

[0016] In one embodiment, the invention discloses a method for modulating the activity of a NOVX polypeptide. The method includes the steps of: introducing a cell sample expressing the NOVX polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide. In another embodiment, the invention includes an isolated NOVX nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising a NOVX amino acid sequence or a variant of a mature form of the NOVX amino acid sequence, wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed. In another embodiment, the invention includes an amino acid sequence that is a variant of the NOVX amino acid sequence, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed.

[0017] In one embodiment, the invention discloses a NOVX nucleic acid fragment encoding at least a portion of a NOVX polypeptide or any variant of the polypeptide, wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed. In another embodiment, the invention includes the complement of any of the NOVX nucleic acid molecules or a naturally occurring allelic nucleic acid variant. In another embodiment, the invention discloses a NOVX nucleic acid molecule that encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant. In another embodiment, the invention discloses a NOVX nucleic acid, wherein the nucleic acid molecule differs by a single nucleotide from a NOVX nucleic acid sequence.

[0018] In another aspect, the invention includes a NOVX nucleic acid, wherein one or more nucleotides in the NOVX nucleotide sequence is changed to a different nucleotide provided that no more than 15% of the nucleotides are so changed. In one embodiment, the invention discloses a nucleic acid fragment of the NOVX nucleotide sequence and a nucleic acid fragment wherein one or more nucleotides in the NOVX nucleotide sequence is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed. In another embodiment, the invention includes a nucleic acid molecule wherein the nucleic acid molecule hybridizes under stringent conditions to a NOVX nucleotide sequence or a complement of the NOVX nucleotide sequence. In one embodiment, the invention includes a nucleic acid molecule, wherein the sequence is changed such that no more than 15% of the nucleotides in the coding sequence differ from the NOVX nucleotide sequence or a fragment thereof.

[0019] In a further aspect, the invention includes a method for determining the presence or amount of the NOVX nucleic acid in a sample. The method involves the steps of: providing the sample; introducing the sample to a probe that binds to the nucleic acid molecule; and determining the presence or amount of the probe bound to the NOVX nucleic acid molecule, thereby determining the presence or amount of the NOVX nucleic acid molecule in the sample. In one embodiment, the presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type.

[0020] In another aspect, the invention discloses a method for determining the presence of or predisposition to a disease associated with altered levels of the NOVX nucleic acid molecule of in a first mammalian subject. The method involves the steps of measuring the amount of NOVX nucleic acid in a sample from the first mammalian subject; and comparing the amount of the nucleic acid in the sample of step (a) to the amount of NOVX nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

[0021] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

[0022] Other features and advantages of the invention will be apparent from the following detailed description and claims.

DETAILED DESCRIPTION OF THE INVENTION

[0023] The present invention provides novel nucleotides and polypeptides encoded thereby. Included in the invention are the novel nucleic acid sequences, their encoded polypeptides, antibodies, and other related compounds. The sequences are collectively referred to herein as “NOVX nucleic acids” or “NOVX polynucleotides” and the corresponding encoded polypeptides are referred to as “NOVX polypeptides” or “NOVX proteins.” Unless indicated otherwise, “NOVX” is meant to refer to any of the novel sequences disclosed herein. Table A provides a summary of the NOVX nucleic acids and their encoded polypeptides.

TABLE A
Sequences and Corresponding SEQ ID Numbers
		SEQ ID	SEQ ID
		NO	NO
NOVX	Internal	(nucleic	(amino
Assignment	Identification	acid)	acid)	Homology
1	CG100073-01	1	2	TASTE RECEPTOR T1R1
2a	CG103679-02	3	4	Asparaginase like homo sapiens
2b	CG103679-03	5	6	Asparaginase like homo sapiens
2c	CG103679-06	7	8	Asparaginase like homo sapiens
2d	CG103679-07	9	10	Asparaginase like homo sapiens
2e	209770546	11	12	Asparaginase like homo sapiens
2f	209770585	13	14	Asparaginase like homo sapiens
2g	209770611	15	16	Asparaginase like homo sapiens
3	CG109541-01	17	18	GPCR
4a	CG110223-01	19	20	Alpha-N-Acetylgalactosaminide Alpha-2,6-
				Sialyltransferase like homo sapiens
4b	CG110223-02	21	22	Alpha-N-Acetylgalatosaminide Alpha-2,6-
				Sialyltransferase like homo sapiens
4c	CG110223-03	23	24	Alpha-N-Acctylgalactosaminide Alpha-2,6-
				Sialyltransferase like homo sapiens
5	CG110311-01	25	26	MANNOSIDASE like homo sapiens
6a	CG110421-01	27	28	Peroxisomal Short-Chain A1cohol
				Dehydrogenase 2 like homo sapiens
6b	CG110421-02	29	30	Peroxisomal Short-Chain A1cohol
				Dehydrogenase 2 like homo sapiens
7a	CG110531-01	31	32	PROTEASOME SUBUNIT ALPHA TYPE 7
				(EC 3.4.99.46) (PROTEASOME SUBUNIT
				ALPHA 4) like homo sapiens
7b	CG110531-02	33	34	PROTEASOME SUBUNIT ALPHA TYPE 7
				(EC 3.4 99.46) (PROTEASOME SUBUNIT
				ALPHA 4) like homo sapiens
8	CG111231-01	35	36	Galactosyltransferase like homo sapiens
9a	CG111293-02	37	38	Protoporphyrinogen oxidase like homo sapiens
9b	CG111293-03	39	40	Protoporphyrinogen oxidase like homo sapiens
9c	CG111293-04	41	42	Protoporphyrinogen oxidase like homo sapiens
9d	CG111293-05	43	44	Protoporphyrinogen oxidase like homo sapiens
9e	CG111293-06	45	46	Protoporphyrinogen oxidase like homo sapiens
10	CG111455-01	47	48	Myosin Heavy Chain like homo sapiens
11a	CG112292-02	49	50	Aquaporin like homo sapiens
11b	CG112292-04	51	52	Aquaporin like homo sapiens
11c	CG112292-05	53	54	Aquaporin like homo sapiens
12	CG112722-01	55	56	EPOXIDE HYDROLASE like homo sapiens
13	CG112881-02	57	58	Angiotensin II Receptor like homo sapiens
14	CG113803-01	59	60	KIF21A like homo sapiens
15	CG113833-01	61	62	RETINOIC ACID RECEPTOR RXR-ALPHA
				like homo sapiens
16a	CG114150-01	63	64	Type I membrane protein like homo sapiens
16b	210982611	65	66	Type I membrane protein like homo sapiens
16c	211546798	67	68	Type I membrane protein like homo sapiens
16d	211546812	69	70	Type I membrane protein like homo sapiens
16e	211546816	71	72	Type I membrane protein like homo sapiens
16f	211546824	73	74	Type I membrane protein like homo sapiens
17a	CG114555-01	75	76	facilitative glucose transporter family member
				GLUT9 like homo sapiens
17b	CG114555-03	77	78	facilitative glucose transporter family member
				GLUT9 like homo sapiens
17c	CG114555-04	79	80	facilitative glucose transporter family member
				GLUT9 like homo sapiens
17d	247847070	81	82	facilitative glucose transporter family number
				GLUT9 like homo sapiens
17e	247847059	83	84	facilitative glucose transporter family member
				GLUT9 like homo sapiens
17f	247847055	85	86	facilitative glucose transporter family member
				GLUT9 like homo sapiens
17g	247847047	87	88	facilitative glucose transporter family member
				GLUT9 like homo sapiens
17h	247847078	89	90	facilitative glucose transporter family member
				GLUT9 like homo sapiens
18	CG114784-01	91	92	Signal peptidase Domain Containing Protein
				like homo sapiens
19	CG114886-01	93	94	Mitochondrial Inner Membrane Protease
				Subnunit 2 like homo sapiens
20	CG115411-01	95	96	MYOSIN HEAVY CHAIN PROTEIN I1B like
				homo sapiens
21	CG116270-01	97	98	Endo-alpha-D-Mannosidase homo sapiens
22	CG118160-01	99	100	LATROPHILIN 2 homo sapiens
23	CG119685-01	101	102	Ubiquitin C-terminal hydrolase UCH37 homo
				sapiens
24a	CG120443-01	103	104	Focal adhesion kinase 1 like homo sapiens
24b	CG120443-02	105	106	Focal adhesion kinase 1 like homo sapiens
25a	CG120563-01	107	108	MITOCHONDRIAL ISOLEUCINE TRNA
				SYNTHETASE homo sapiens
25b	CG120563-02	109	110	MITOCHONDRIAL ISOLEUCINE TRNA
				SYNTHETASE-like
26	CG122872-01	111	112	Vacuolar ATP Synthase 16 KDA Proteolipid
				Subunit like homo sapiens
27	CG122909-01	113	114	Ubiquitin Protein Ligase like homo sapiens
28	CG123772-01	115	116	Transporter like homo sapiens
29a	CG124021-01	117	118	KETOHEXOKINASE like homo sapiens
29b	CG124021-02	119	120	KETOHEXOKINASE like homo sapiens
29c	CG124021-04	121	122	KETOHEXOKINASE like homo sapiens
30a	CG150245-01	123	124	AROMATIC-L-AMINO-ACID
				DECARBOXYLASE homo sapiens
30b	CG150245-02	125	126	AROMATIC-L-AMINO-ACID
				DECARBOXYLASE homo sapiens
31	CG55814-02	127	128	glyceraldehyde 3 phosphate dehydrogenase like
				homo sapiens
32a	CG56735-01	129	130	ADAMTS 7 like homo sapiens
32b	CG56735-02	131	132	ADAMTS 7 like homo sapiens
32c	174124733	155	156	ADAMTS 7 like homo sapiens
33a	CG57635-02	133	134	D3,D2-Enoyl-CoA Isomerase−like
33b	CG57635-03	135	136	PEROXISOMAL 3,2-TRANS-ENOYL-COA
				ISOMERASE like homo sapiens
34a	CG96859-02	137	138	Hydroxymethylglutaryl-COA lyase like homo sapiens
34b	CG96859-03	139	140	Hydroxymethylglutaryl-COA lyase like homo sapiens
34c	CG96859-04	141	142	Hydroxymethylglutaryl-COA lyase like homo sapiens
34d	CG96859-05	143	144	Hydroxymethylglutaryl-COA lyase like homo sapiens
34e	212974165	145	146	Hydroxymethylglutaryl-COA lyase like homo sapiens
35	CG98082-01	147	148	TASTE RECEPTOR T1R3
36	CG98102-04	149	150	Diamine Acyltransferase like homo sapiens
37a	CG122863-01	151	152	Membrane protein like
37b	CG122863-02	153	154	Membrane protein like

[0024] Table A indicates the homology of NOVX polypeptides to known protein families. Thus, the nucleic acids and polypeptides, antibodies and related compounds according to the invention corresponding to a NOVX as identified in column 1 of Table A will be useful in therapeutic and diagnostic applications implicated in, for example, pathologies and disorders associated with the known protein families identified in column 5 of Table A.

[0025] Pathologies, diseases, disorders and condition and the like that are associated with NOVX sequences include, but are not limited to: e.g., cardiomyopathy, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, atrial septal defect (ASD), atrioventricular (A-V) canal defect, ductus arteriosus, pulmonary stenosis, subaortic stenosis, ventricular septal defect (VSD), valve diseases, tuberous sclerosis, scleroderma, obesity, metabolic disturbances associated with obesity, transplantation, adrenolcukodystrophy, congenital adrenal hyperplasia, prostate cancer, diabetes, metabolic disorders, neoplasm; adenocarcinoma, lymphoma, uterus cancer, fertility, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, graft versus host disease, AIDS, bronchial asthma, Crohn's disease; multiple sclerosis, treatment of Albright Hereditary Ostocodystrophy, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegencrative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, hematopoietic disorders, and the various dyslipidemias, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers, as well as conditions such as transplantation and fertility.

[0026] NOVX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts. The various NOVX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, NOVX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the NOVX polypeptides belong.

[0027] Consistent with other known members of the family of proteins, identified in column 5 of Table A, the NOVX polypeptides of the present invention show homology to, and contain domains that are characteristic of, other members of such protein families. Details of the sequence relatedness and domain analysis for each NOVX are presented in Example A.

[0028] The NOVX nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance NOVX activity or function. Specifically, the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit diseases associated with the protein families listed in Table A.

[0029] The NOVX nucleic acids and polypeptides are also useful for detecting specific cell types. Details of the expression analysis for each NOVX are presented in Example C. Accordingly, the NOVX nucleic acids, polypeptides, antibodies and related compounds according to the invention will have diagnostic and therapeutic applications in the detection of a variety of diseases with differential expression in normal vs. diseased tissues, e.g. detection of a variety of cancers.

[0030] Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.

[0031] NOVX Clones

[0032] NOVX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts. The various NOVX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, NOVX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the NOVX polypeptides belong.

[0033] The NOVX genes and their corresponding encoded proteins are useful for preventing, treating or ameliorating medical conditions, e.g., by protein or gene therapy. Pathological conditions can be diagnosed by determining the amount of the new protein in a sample or by determining the presence of mutations in the new genes. Specific uses are described for each of the NOVX genes, based on the tissues in which they are most highly expressed. Uses include developing products for the diagnosis or treatment of a variety of diseases and disorders.

[0034] The NOVX nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. These include serving as a specific or selective nucleic acid or protein diagnostic and/or prognostic marker, wherein the presence or amount of the nucleic acid or the protein are to be assessed, as well as potential therapeutic applications such as the following: (i) a protein therapeutic, (ii) a small molecule drug target, (iii) an antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), (iv) a nucleic acid useful in gene therapy (gene delivery/gene ablation), and (v) a composition promoting tissue regeneration in vitro and in vivo (vi) a biological defense weapon.

[0035] In one specific embodiment, the invention includes an isolated polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 78; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 78, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) an amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 78; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 78 wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; and (e) a fragment of any of (a) through (d).

[0036] In another specific embodiment, the invention includes an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence given SEQ ID NO: 2n, wherein n is an integer between 1 and 78; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 78 wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 78; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 78, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; (e) a nucleic acid fragment encoding at least a portion of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 78 or any variant of said polypeptide wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed; and (f) the complement of any of said nucleic acid molecules.

[0037] In yet another specific embodiment, the invention includes an isolated nucleic acid molecule, wherein said nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of: (a) the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 78; (b) a nucleotide sequence wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 78 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed; (c) a nucleic acid fragment of the sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 78; and (d) a nucleic acid fragment wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 78 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed.

[0038] NOVX Nucleic Acids and Polypeptides

[0039] One aspect of the invention pertains to isolated nucleic acid molecules that encode NOVX polypeptides or biologically active portions thereof. Also included in the invention are nucleic acid fragments sufficient for use as hybridization probes to identify NOVX-encoding nucleic acids (e.g., NOVX mRNAs) and fragments for use as PCR primers for the amplification and/or mutation of NOVX nucleic acid molecules. As used herein, the term “nucleic acid molecule” is intended to include DNA molecules (e.g., cDNA or genomic DNA), RNA molecules (e.g., mRNA), analogs of the DNA or RNA generated using nucleotide analogs, and derivatives, fragments and homologs thereof. The nucleic acid molecule may be single-stranded or double-stranded, but preferably is comprised double-stranded DNA.

[0040] A NOVX nucleic acid can encode a mature NOVX polypeptide. As used herein, a “mature” form of a polypeptide or protein disclosed in the present invention is the product of a naturally occurring polypeptide or precursor form or proprotein. The naturally occurring polypeptide, precursor or proprotein includes, by way of nonlimiting example, the full-length gene product encoded by the corresponding gene. Alternatively, it may be defined as the polypeptide, precursor or proprotein encoded by an ORF described herein. The product “mature” form arises, by way of nonlimiting example, as a result of one or more naturally occurring processing steps that may take place within the cell (e.g., host cell) in which the gene product arises. Examples of such processing steps leading to a “mature” form of a polypeptide or protein include the cleavage of the N-terminal methionine residue encoded by the initiation codon of an ORF, or the proteolytic cleavage of a signal peptide or leader sequence. Thus a mature form arising from a precursor polypeptide or protein that has residues 1 to N, where residue 1 is the N-terminal methionine, would have residues 2 through N remaining after removal of the N-terminal methionine. Alternatively, a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an N-terminal signal sequence from residue 1 to residue M is cleaved, would have the residues from residue M+1 to residue N remaining. Further as used herein, a “mature” form of a polypeptide or protein may arise from a step of post-translational modification other than a proteolytic cleavage event. Such additional processes include, by way of non-limiting example, glycosylation, myristylation or phosphorylation. In general, a mature polypeptide or protein may result from the operation of only one of these processes, or a combination of any of them.

[0041] The term “probe”, as utilized herein, refers to nucleic acid sequences of variable length, preferably between at least about 10 nucleotides (nt), about 100 nt, or as many as approximately, e g, 6,000 nt, depending upon the specific use. Probes are used in the detection of identical, similar, or complementary nucleic acid sequences. Longer length probes are generally obtained from a natural or recombinant source, are highly specific, and much slower to hybridize than shorter-length oligomer probes. Probes may be single-stranded or double-stranded and designed to have specificity in PCR, membrane-based hybridization technologies, or ELISA-like technologies.

[0042] The term “isolated” nucleic acid molecule, as used herein, is a nucleic acid that is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. Preferably, an “isolated” nucleic acid is free of sequences which naturally flank the nucleic acid (i e., sequences located at the 5′- and 3′-termini of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated NOVX nucleic acid molecules can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell/tissue from which the nucleic acid is derived (e g., brain, heart, liver, spleen, etc ). Moreover, an “isolated” nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material, or culture medium, or of chemical precursors or other chemicals.

[0043] A nucleic acid molecule of the invention, e.g, a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, or a complement of this nucleotide sequence, can be isolated using standard molecular biology techniques and the sequence information provided herein. Using all or a portion of the nucleic acid sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, as a hybridization probe, NOVX molecules can be isolated using standard hybridization and cloning techniques (e.g., as described in Sambrook, et al., (eds.), Molecular Cloning: A Laboratory Manual 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989; and Ausubel, et al., (eds.), Current Protocols in Molecular Biology, John Wiley & Sons, New York, N.Y., 1993.)

[0044] A nucleic acid of the invention can be amplified using cDNA, mRNA or alternatively, genomic DNA, as a template with appropriate oligonucleotide primers according to standard PCR amplification techniques. The nucleic acid so amplified can be cloned into an appropriate vector and characterized by DNA sequence analysis. Furthermore, oligonucleotides corresponding to NOVX nucleotide sequences can be prepared by standard synthetic techniques, e.g., using an automated DNA synthesizer.

[0045] As used herein, the term “oligonucleotide” refers to a series of linked nucleotide residues. A short oligonucleotide sequence may be based on, or designed from, a genomic or cDNA sequence and is used to amplify, confirm, or reveal the presence of an identical, similar or complementary DNA or RNA in a particular cell or tissue. Oligonucleotides comprise a nucleic acid sequence having about 10 nt, 50 nt, or 100 nt in length, preferably about 15 nt to 30 nt in length. In one embodiment of the invention, an oligonucleotide comprising a nucleic acid molecule less than 100 nt in length would further comprise at least 6 contiguous nucleotides of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.

[0046] In another embodiment, an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule that is a complement of the nucleotide sequence shown in SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, or a portion of this nucleotide sequence (e.g., a fragment that can be used as a probe or primer or a fragment encoding a biologically-active portion of a NOVX polypeptide). A nucleic acid molecule that is complementary to the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, is one that is sufficiently complementary to the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, that it can hydrogen bond with few or no mismatches to the nucleotide sequence shown in SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, thereby forming a stable duplex.

[0047] As used herein, the term “complementary” refers to Watson-Crick or Hoogsteen base pairing between nucleotides units of a nucleic acid molecule, and the term “binding” means the physical or chemical interaction between two polypeptides or compounds or associated polypeptides or compounds or combinations thereof. Binding includes ionic, non-ionic, van der Waals, hydrophobic interactions, and the like. A physical interaction can be either direct or indirect. Indirect interactions may be through or due to the effects of another polypeptide or compound. Direct binding refers to interactions that do not take place through, or due to, the effect of another polypeptide or compound, but instead are without other substantial chemical intermediates.

[0048] A “fragment” provided herein is defined as a sequence of at least 6 (contiguous) nucleic acids or at least 4 (contiguous) amino acids, a length sufficient to allow for specific hybridization in the case of nucleic acids or for specific recognition of an epitope in the case of amino acids, and is at most some portion less than a full length sequence. Fragments may be derived from any contiguous portion of a nucleic acid or amino acid sequence of choice.

[0049] A full-length NOVX clone is identified as containing an ATG translation start codon and an in-frame stop codon. Any disclosed NOVX nucleotide sequence lacking an ATG start codon therefore encodes a truncated C-terminal fragment of the respective NOVX polypeptide, and requires that the corresponding full-length cDNA extend in the 5′ direction of the disclosed sequence. Any disclosed NOVX nucleotide sequence lacking an in-frame stop codon similarly encodes a truncated N-terminal fragment of the respective NOVX polypeptide, and requires that the corresponding full-length cDNA extend in the 3′ direction of the disclosed sequence.

[0050] A “derivative” is a nucleic acid sequence or amino acid sequence formed from the native compounds either directly, by modification or partial substitution. An “analog” is a nucleic acid sequence or amino acid sequence that has a structure similar to, but not identical to, the native compound, e g. they differs from it in respect to certain components or side chains. Analogs may be synthetic or derived from a different evolutionary origin and may have a similar or opposite metabolic activity compared to wild type. A “homolog” is a nucleic acid sequence or amino acid sequence of a particular gene that is derived from different species.

[0051] Derivatives and analogs may be full length or other than full length. Derivatives or analogs of the nucleic acids or proteins of the invention include, but are not limited to, molecules comprising regions that are substantially homologous to the nucleic acids or proteins of the invention, in various embodiments, by at least about 70%, 80%, or 95% identity (with a preferred identity of 80-95%) over a nucleic acid or amino acid sequence of identical size or when compared to an aligned sequence in which the alignment is done by a computer homology program known in the art, or whose encoding nucleic acid is capable of hybridizing to the complement of a sequence encoding the proteins under stringent, moderately stringent, or low stringent conditions. See e.g. Ausubel, et al., Current Protocols in Molecular Biology, John Wiley & Sons, New York, N.Y., 1993, and below.

[0052] A “homologous nucleic acid sequence” or “homologous amino acid sequence,” or variations thereof, refer to sequences characterized by a homology at the nucleotide level or amino acid level as discussed above. Homologous nucleotide sequences include those sequences coding for isoforms of NOVX polypeptides. Isoforms can be expressed in different tissues of the same organism as a result of, for example, alternative splicing of RNA. Alternatively, isoforms can be encoded by different genes. In the invention, homologous nucleotide sequences include nucleotide sequences encoding for a NOVX polypeptide of species other than humans, including, but not limited to: vertebrates, and thus can include, e.g., frog, mouse, rat, rabbit, dog, cat cow, horse, and other organisms. Homologous nucleotide sequences also include, but are not limited to, naturally occurring allelic variations and mutations of the nucleotide sequences set forth herein. A homologous nucleotide sequence does not, however, include the exact nucleotide sequence encoding human NOVX protein. Homologous nucleic acid sequences include those nucleic acid sequences that encode conservative amino acid substitutions (see below) in SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.

[0053] A NOVX polypeptide is encoded by the open reading frame (“ORF”) of a NOVX nucleic acid. An ORF corresponds to a nucleotide sequence that could potentially be translated into a polypeptide. A stretch of nucleic acids comprising an ORF is uninterrupted by a stop codon. An ORF that represents the coding sequence for a full protein begins with an ATG “start” codon and terminates with one of the three “stop” codons, namely, TAA, TAG, or TGA. For the purposes of this invention, an ORF may be any part of a coding sequence, with or without a start codon, a stop codon, or both. For an ORF to be considered as a good candidate for coding for a bona fide cellular protein, a minimum size requirement is often set, e.g., a stretch of DNA that would encode a protein of 50 amino acids or more.

[0054] The nucleotide sequences determined from the cloning of the human NOVX genes allows for the generation of probes and primers designed for use in identifying and/or cloning NOVX homologues in other cell types, e.g. from other tissues, as well as NOVX homologues from other vertebrates. The probe/primer typically comprises substantially purified oligonucleotide. The oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12, 25, 50, 100, 150, 200, 250, 300, 350 or 400 consecutive sense strand nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78; or an anti-sense strand nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78; or of a naturally occurring mutant of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78.

[0055] Probes based on the human NOVX nucleotide sequences can be used to detect transcripts or genomic sequences encoding the same or homologous proteins. in various embodiments, the probe has a detectable label attached, e.g the label can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme co-factor. Such probes can be used as a part of a diagnostic test kit for identifying cells or tissues which mis-express a NOVX protein, such as by measuring a level of a NOVX-encoding nucleic acid in a sample of cells from a subject e g., detecting NOVX mRNA levels or determining whether a genomic NOVX gene has been mutated or deleted.

[0056] “A polypeptide having a biologically-active portion of a NOVX polypeptide” refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. A nucleic acid fragment encoding a “biologically-active portion of NOVX” can be prepared by isolating a portion of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, that encodes a polypeptide having a NOVX biological activity (the biological activities of the NOVX proteins are described below), expressing the encoded portion of NOVX protein (e.g., by recombinant expression in vitro) and assessing the activity of the encoded portion of NOVX.

[0057] NOVX Nucleic Acid and Polypeptide Variants

[0058] The invention further encompasses nucleic acid molecules that differ from the nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, due to degeneracy of the genetic code and thus encode the same NOVX proteins as that encoded by the nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78. In another embodiment, an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a protein having an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 78.

[0059] In addition to the human NOVX nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, it will be appreciated by those skilled in the art that DNA sequence polymorphisms that lead to changes in the amino acid sequences of the NOVX polypeptides may exist within a population (e g, the human population). Such genetic polymorphism in the NOVX genes may exist among individuals within a population due to natural allelic variation. As used herein, the terms “gene” and “recombinant gene” refer to nucleic acid molecules comprising an open reading frame (ORF) encoding a NOVX protein, preferably a vertebrate NOVX protein. Such natural allelic variations can typically result in 1-5% variance in the nucleotide sequence of the NOVX genes. Any and all such nucleotide variations and resulting amino acid polymorphisms in the NOVX polypeptides, which are the result of natural allelic variation and that do not alter the functional activity of the NOVX polypeptides, are intended to be within the scope of the invention.

[0060] Moreover, nucleic acid molecules encoding NOVX proteins from other species, and thus that have a nucleotide sequence that differs from a human SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, are intended to be within the scope of the invention. Nucleic acid molecules corresponding to natural allelic variants and homologues of the NOVX cDNAs of the invention can be isolated based on their homology to the human NOVX nucleic acids disclosed herein using the human cDNAs, or a portion thereof, as a hybridization probe according to standard hybridization techniques under stringent hybridization conditions.

[0061] Accordingly, in another embodiment, an isolated nucleic acid molecule of the invention is at least 6 nucleotides in length and hybridizes under stringent conditions to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78. In another embodiment, the nucleic acid is at least 10, 25, 50, 100, 250, 500, 750, 1000, 1500, or 2000 or more nucleotides in length. In yet another embodiment, an isolated nucleic acid molecule of the invention hybridizes to the coding region. As used herein, the term “hybridizes under stringent conditions” is intended to describe conditions for hybridization and washing under which nucleotide sequences at least about 65% homologous to each other typically remain hybridized to each other.

[0062] Homologs (i.e., nucleic acids encoding NOVX proteins derived from species other than human) or other related sequences (e.g., paralogs) can be obtained by low, moderate or high stringency hybridization with all or a portion of the particular human sequence as a probe using methods well known in the art for nucleic acid hybridization and cloning.

[0063] As used herein, the phrase “stringent hybridization conditions” refers to conditions under which a probe, primer or oligonucleotide will hybridize to its target sequence, but to no other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures than shorter sequences. Generally, stringent conditions are selected to be about 5° C. lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH. The Tm is the temperature (under defined ionic strength, pH and nucleic acid concentration) at which 50% of the probes complementary to the target sequence hybridize to the target sequence at equilibrium. Since the target sequences are generally present at excess, at Tm, 50% of the probes are occupied at equilibrium. Typically, stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30° C. for short probes, primers or oligonucleotides (e g., 10 nt to 50 nt) and at least about 60° C. for longer probes, primers and oligonucleotides. Stringent conditions may also be achieved with the addition of destabilizing agents, such as formamide.

[0064] Stringent conditions are known to those skilled in the art and can be found in Ausubel, et al., (eds.), Current Protocols in Molecular Biology, John Wiley & Sons, N.Y. (1989), 6.3.1-6.3.6. Preferably, the conditions are such that sequences at least about 65%, 70%, 75%, 85%, 90%, 95%, 98%, or 99% homologous to each other typically remain hybridized to each other. A non-limiting example of stringent hybridization conditions are hybridization in a high salt buffer comprising 6×SSC, 50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.02% BSA, and 500 mg/ml denatured salmon sperm DNA at 65° C., followed by one or more washes in 0.2×SSC, 0.01% BSA at 50° C. An isolated nucleic acid molecule of the invention that hybridizes under stringent conditions to a sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, corresponds to a naturally-occurring nucleic acid molecule. As used herein, a “naturally-occurring” nucleic acid molecule refers to an RNA or DNA molecule having a nucleotide sequence that occurs in nature (e.g., encodes a natural protein).

[0065] In a second embodiment, a nucleic acid sequence that is hybridizable to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, or fragments, analogs or derivatives thereof, under conditions of moderate stringency is provided. A non-limiting example of moderate stringency hybridization conditions are hybridization in 6×SSC, 5×Reinhardt's solution, 0.5% SDS and 100 mg/ml denatured salmon sperm DNA at 55° C., followed by one or more washes in 1×SSC, 0.1% SDS at 37° C. Other conditions of moderate stringency that may be used are well-known within the art. See, e.g., Ausubel, et al. (eds.), 1993, Current Protocols in Molecular Biology, John Wiley & Sons, NY, and Krieger, 1990; Gene Transfer and Expression, a Laboratory Manual, Stockton Press, NY.

[0066] In a third embodiment, a nucleic acid that is hybridizable to the nucleic acid molecule comprising the nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting example of low stringency hybridization conditions are hybridization in 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg/ml denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40° C., followed by one or more washes in 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS at 50° C. Other conditions of low stringency that may be used are well known in the art (e.g., as employed for cross-species hybridizations). See, e.g., Ausubel, et al. (eds.), 1993, Current Protocols in Molecular Biology, John Wiley & Sons, NY, and Kriegler, 1990, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY; Shilo and Weinberg, 1981. Proc Natl Acad Sci USA 78: 6789-6792.

[0067] Conservative Mutations

[0068] In addition to naturally-occurring allelic variants of NOVX sequences that may exist in the population, the skilled artisan will further appreciate that changes can be introduced by mutation into the nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, thereby leading to changes in the amino acid sequences of the encoded NOVX protein, without altering the functional ability of that NOVX protein. For example, nucleotide substitutions leading to amino acid substitutions at “non-essential” amino acid residues can be made in the sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 78. A “non-essential” amino acid residue is a residue that can be altered from the wild-type sequences of the NOVX proteins without altering their biological activity, whereas an “essential” amino acid residue is required for such biological activity. For example, amino acid residues that are conserved among the NOVX proteins of the invention are predicted to be particularly non-amenable to alteration. Amino acids for which conservative substitutions can be made are well-known within the art.

[0069] Another aspect of the invention pertains to nucleic acid molecules encoding NOVX proteins that contain changes in amino acid residues that are not essential for activity. Such NOVX proteins differ in amino acid sequence from SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, yet retain biological activity. In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises an amino acid sequence at least about 40% homologous to the amino acid sequences of SEQ ID NO:2n, wherein n is an integer between 1 and 78. Preferably, the protein encoded by the nucleic acid molecule is at least about 60% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 78; more preferably at least about 70% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 78; still more preferably at least about 80% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 78; even more preferably at least about 90% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 78; and most preferably at least about 95% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 78.

[0070] An isolated nucleic acid molecule encoding a NOVX protein homologous to the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 78, can be created by introducing one or more nucleotide substitutions, additions or deletions into the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.

[0071] Mutations can be introduced any one of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more predicted, non-essential amino acid residues. A “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined within the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a predicted non-essential amino acid residue in the NOVX protein is replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of a NOVX coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for NOVX biological activity to identify mutants that retain activity. Following mutagenesis of a nucleic acid of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.

[0072] The relatedness of amino acid families may also be determined based on side chain interactions. Substituted amino acids may be fully conserved “strong” residues or fully conserved “weak” residues. The “strong” group of conserved amino acid residues may be any one of the following groups: STA, NEQK, NHQK, NDEQ, QHRK, MILV, MILF, HY, FYW, wherein the single letter amino acid codes are grouped by those amino acids that may be substituted for each other. Likewise, the “weak” group of conserved residues may be any one of the following: CSA, ATV, SAG, STNK, STPA, SGND, SNDEQK, NDEQHK, NEQHRK, HFY, wherein the letters within each group represent the single letter amino acid code.

[0073] In one embodiment, a mutant NOVX protein can be assayed for (i) the ability to form protein:protein interactions with other NOVX proteins, other cell-surface proteins, or biologically-active portions thereof, (ii) complex formation between a mutant NOVX protein and a NOVX ligand; or (iii) the ability of a mutant NOVX protein to bind to an intracellular target protein or biologically-active portion thereof, (e.g. avidin proteins).

[0074] In yet another embodiment, a mutant NOVX protein can be assayed for the ability to regulate a specific biological function (e g., regulation of insulin release).

[0075] Antisense Nucleic Acids

[0076] Another aspect of the invention pertains to isolated antisense nucleic acid molecules that are hybridizable to or complementary to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, or fragments, analogs or derivatives thereof. An “antisense” nucleic acid comprises a nucleotide sequence that is complementary to a “sense” nucleic acid encoding a protein (e.g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA sequence). In specific aspects, antisense nucleic acid molecules are provided that comprise a sequence complementary to at least about 10, 25, 50, 100, 250 or 500 nucleotides or an entire NOVX coding strand, or to only a portion thereof. Nucleic acid molecules encoding fragments, homologs, derivatives and analogs of a NOVX protein of SEQ ID NO:2n, wherein n is an integer between 1 and 78, or antisense nucleic acids complementary to a NOVX nucleic acid sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, are additionally provided.

[0077] In one embodiment, an antisense nucleic acid molecule is antisense to a “coding region” of the coding strand of a nucleotide sequence encoding a NOVX protein. The term “coding region” refers to the region of the nucleotide sequence comprising codons which are translated into amino acid residues. In another embodiment, the antisense nucleic acid molecule is antisense to a “noncoding region” of the coding strand of a nucleotide sequence encoding the NOVX protein. The term “noncoding region” refers to 5′ and 3′ sequences which flank the coding region that are not translated into amino acids (i.e., also referred to as 5′ and 3′ untranslated regions).

[0078] Given the coding strand sequences encoding the NOVX protein disclosed herein, antisense nucleic acids of the invention can be designed according to the rules of Watson and Crick or Hoogsteen base pairing. The antisense nucleic acid molecule can be complementary to the entire coding region of NOVX mRNA, but more preferably is an oligonucleotide that is antisense to only a portion of the coding or noncoding region of NOVX mRNA. For example, the antisense oligonucleotide can be complementary to the region surrounding the translation start site of NOVX mRNA. An antisense oligonucleotide can be, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 nucleotides in length. An antisense nucleic acid of the invention can be constructed using chemical synthesis or enzymatic ligation reactions using procedures known in the art. For example, an antisense nucleic acid (e.g., an antisense oligonucleotide) can be chemically synthesized using naturally-occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids (e.g., phosphorothioate derivatives and acridine substituted nucleotides can be used).

[0079] Examples of modified nucleotides that can be used to generate the antisense nucleic acid include: 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-carboxymethylaminomethyl-2-thiouridine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 5-methoxyuracil, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methlylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, 2-thiouracil, 4-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminiopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).

[0080] The antisense nucleic acid molecules of the invention are typically administered to a subject or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding a NOVX protein to thereby inhibit expression of the protein (e.g., by inhibiting transcription and/or translation). The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule that binds to DNA duplexes, through specific interactions in the major groove of the double helix. An example of a route of administration of antisense nucleic acid molecules of the invention includes direct injection at a tissue site. Alternatively, antisense nucleic acid molecules can be modified to target selected cells and then administered systemically. For example, for systemic administration, antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface (e.g., by linking the antisense nucleic acid molecules to peptides or antibodies that bind to cell surface receptors or antigens). The antisense nucleic acid molecules can also be delivered to cells using the vectors described herein. To achieve sufficient nucleic acid molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong pol II or pol III promoter are preferred.

[0081] In yet another embodiment, the antisense nucleic acid molecule of the invention is an α-anomeric nucleic acid molecule. An α-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual β-units, the strands run parallel to each other. See, e.g., Gaultier, et al., 1987. Nucl. Acids Res. 15: 6625-6641. The antisense nucleic acid molecule can also comprise a 2′-o-methylribonucleotide (See, e g, Inoue, et al. 1987. Nucl. Acids Res. 15: 6131-6148) or a chimeric RNA-DNA analogue (See, e.g., Inoue, et al., 1987. FEBS Lett. 215: 327-330.

[0082] Ribozymes and PNA Moieties

[0083] Nucleic acid modifications include, by way of non-limiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject.

[0084] In one embodiment, an antisense nucleic acid of the invention is a ribozyme. Ribozymes are catalytic RNA molecules with ribonuclease activity that are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes (e.g., hammerhead ribozymes as described in Haselhoff and Gerlach 1988. Nature 334: 585-591) can be used to catalytically cleave NOVX mRNA transcripts to thereby inhibit translation of NOVX mRNA. A ribozyme having specificity for a NOVX-encoding nucleic acid can be designed based upon the nucleotide sequence of a NOVX cDNA disclosed herein (i.e., SEQ ID NO:2n-1, wherein n is an integer between 1 and 78). For example, a derivative of a Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in a NOVX-encoding mRNA. See, e.g., U.S. Pat. No. 4,987,071 to Cech, et al. and U.S. Pat. No. 5,116,742 to Cech, et al. NOVX mRNA can also be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules. See, e.g., Bartel et al., (1993) Science 261:1411-1418.

[0085] Alternatively, NOVX gene expression can be inhibited by targeting nucleotide sequences complementary to the regulatory region of the NOVX nucleic acid (e.g., the NOVX promoter and/or enhancers) to form triple helical structures that prevent transcription of the NOVX gene in target cells. See, e.g., Helene, 1991. Anticancer Drug Des. 6: 569-84; Helene, et al. 1992. Ann. N.Y. Acad. Sci. 660: 27-36; Maher, 1992. Bioassays 14: 807-15.

[0086] In various embodiments, the NOVX nucleic acids can be modified at the base moiety, sugar moiety or phosphate backbone to improve, e.g., the stability, hybridization, or solubility of the molecule. For example, the deoxyribose phosphate backbone of the nucleic acids can be modified to generate peptide nucleic acids. See, e.g, Hyrup, et al., 1996. Bioorg Med Chem 4: 5-23. As used herein, the terms “peptide nucleic acids” or “PNAs” refer to nucleic acid mimics (e.g., DNA mimics) in which the deoxyribose phosphate backbone is replaced by a pseudopeptide backbone and only the four natural nucleotide bases are retained. The neutral backbone of PNAs has been shown to allow for specific hybridization to DNA and RNA under conditions of low ionic strength. The synthesis of PNA oligomer can be performed using standard solid phase peptide synthesis protocols as described in Hyrup, et al., 1996. supra; Perry-O'Keefe, et al., 1996. Proc. Natl. Acad. Sci. USA 93: 14670-14675.

[0087] PNAs of NOVX can be used in therapeutic and diagnostic applications. For example, PNAs can be used as antisense or antigene agents for sequence-specific modulation of gene expression by, e.g., inducing transcription or translation arrest or inhibiting replication. PNAs of NOVX can also be used, for example, in the analysis of single base pair mutations in a gene (e.g., PNA directed PCR clamping; as artificial restriction enzymes when used in combination with other enzymes, e.g., S1 nucleases (See, Hyrup, et al., 1996.supra); or as probes or primers for DNA sequence and hybridization (See, Hyrup, et al., 1996, supra; Perry-O'Keefe, et al., 1996. supra).

[0088] In another embodiment, PNAs of NOVX can be modified, e.g., to enhance their stability or cellular uptake, by attaching lipophilic or other helper groups to PNA, by the formation of PNA-DNA chimeras, or by the use of liposomes or other techniques of drug delivery known in the art. For example, PNA-DNA chimeras of NOVX can be generated that may combine the advantageous properties of PNA and DNA. Such chimeras allow DNA recognition enzymes (e.g, RNase H and DNA polymerases) to interact with the DNA portion while the PNA portion would provide high binding affinity and specificity. PNA-DNA chimeras can be linked using linkers of appropriate lengths selected in terms of base stacking, number of bonds between the nucleotide bases, and orientation (see, Hyrup, et al., 1996. supra). The synthesis of PNA-DNA chimeras can be performed as described in Hyrup, et al, 1996. supra and Finn, et al., 1996. Nucl Acids Res 24: 3357-3363. For example, a DNA chain can be synthesized on a solid support using standard phosphoramidite coupling chemistry, and modified nucleoside analogs, e.g, 5′-(4-methoxytrityl)amino-5′-deoxy-thymidine phosphoramidite, can be used between the PNA and the 5′ end of DNA. See, e.g, Mag, et al., 1989. Nucl Acid Res 17: 5973-5988. PNA monomers are then coupled in a stepwise manner to produce a chimeric molecule with a 5′ PNA segment and a 3′ DNA segment. See, e.g., Finn, et al., 1996. supra. Alternatively, chimeric molecules can be synthesized with a 5′ DNA segment and a 3′ PNA segment. See, e.g., Petersen, et al., 1975. Bioorg. Med. Chem. Lett. 5: 1119-11124.

[0089] In other embodiments, the oligonucleotide may include other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger, et al., 1989. Proc. Natl Acad. Sci U.S.A. 86: 6553-6556; Lemaitre, et al., 1987. Proc. Natl. Acad. Sci. 84: 648-652; PCT Publication No. WO88/09810) or the blood-brain barrier (see, e.g., PCT Publication No. WO 89/10134). In addition, oligonucleotides can be modified with hybridization triggered cleavage agents (see, e.g., Krol, et al., 1988. BioTechniques 6:958-976) or intercalating agents (see, e.g., Zon, 1988. Pharm. Res. 5: 539-549). To this end, the oligonucleotide may be conjugated to another molecule, e.g, a peptide, a hybridization triggered cross-linking agent, a transport agent, a hybridization-triggered cleavage agent, and the like.

[0090] NOVX Polypeptides

[0091] A polypeptide according to the invention includes a polypeptide including the amino acid sequence of NOVX polypeptides whose sequences are provided in any one of SEQ ID NO:2n, wherein n is an integer between 1 and 78. The invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residues shown in any one of SEQ ID NO:2n, wherein n is an integer between 1 and 78, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.

[0092] In general, a NOVX variant that preserves NOVX-like function includes any variant in which residues at a particular position in the sequence have been substituted by other amino acids, and further include the possibility of inserting an additional residue or residues between two residues of the parent protein as well as the possibility of deleting one or more residues from the parent sequence. Any amino acid substitution, insertion, or deletion is encompassed by the invention. In favorable circumstances, the substitution is a conservative substitution as defined above.

[0093] One aspect of the invention pertains to isolated NOVX proteins, and biologically-active portions thereof, or derivatives, fragments, analogs or homologs thereof. Also provided are polypeptide fragments suitable for use as immunogens to raise anti-NOVX antibodies. In one embodiment, native NOVX proteins can be isolated from cells or tissue sources by an appropriate purification scheme using standard protein purification techniques. In another embodiment, NOVX proteins are produced by recombinant DNA techniques. Alternative to recombinant expression, a NOVX protein or polypeptide can be synthesized chemically using standard peptide synthesis techniques.

[0094] An “isolated” or “purified” polypeptide or protein or biologically-active portion thereof is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the NOVX protein is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized. The language “substantially free of cellular material” includes preparations of NOVX proteins in which the protein is separated from cellular components of the cells from which it is isolated or recombinantly-produced. In one embodiment, the language “substantially free of cellular material” includes preparations of NOVX proteins having less than about 30% (by dry weight) of non-NOVX proteins (also referred to herein as a “contaminating protein”), more preferably less than about 20% of non-NOVX proteins, still more preferably less than about 10% of non-NOVX proteins, and most preferably less than about 5% of non-NOVX proteins. When the NOVX protein or biologically-active portion thereof is recombinantly-produced, it is also preferably substantially free of culture medium, i.e., culture medium represents less than about 20%, more preferably less than about 10%, and most preferably less than about 5% of the volume of the NOVX protein preparation.

[0095] The language “substantially free of chemical precursors or other chemicals” includes preparations of NOVX proteins in which the protein is separated from chemical precursors or other chemicals that are involved in the synthesis of the protein. In one embodiment, the language “substantially free of chemical precursors or other chemicals” includes preparations of NOVX proteins having less than about 30% (by dry weight) of chemical precursors or non-NOVX chemicals, more preferably less than about 20% chemical precursors or non-NOVX chemicals, still more preferably less than about 10% chemical precursors or non-NOVX chemicals, and most preferably less than about 5% chemical precursors or non-NOVX chemicals.

[0096] Biologically-active portions of NOVX proteins include peptides comprising amino acid sequences sufficiently homologous to or derived from the amino acid sequences of the NOVX proteins (e.g., the amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 78) that include fewer amino acids than the full-length NOVX proteins, and exhibit at least one activity of a NOVX protein. Typically, biologically-active portions comprise a domain or motif with at least one activity of the NOVX protein. A biologically-active portion of a NOVX protein can be a polypeptide which is, for example, 10, 25, 50, 100 or more amino acid residues in length.

[0097] Moreover, other biologically-active portions, in which other regions of the protein are deleted, can be prepared by recombinant techniques and evaluated for one or more of the functional activities of a native NOVX protein.

[0098] In an embodiment, the NOVX protein has an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 78. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 78, and retains the functional activity of the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 78, yet differs in amino acid sequence due to natural allelic variation or mutagenesis, as described in detail, below. Accordingly, in another embodiment, the NOVX protein is a protein that comprises an amino acid sequence at least about 45% homologous to the amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 78, and retains the functional activity of the NOVX proteins of SEQ ID NO:2n, wherein n is an integer between 1 and 78.

[0099] Determining Homology Between Two or More Sequences

[0100] To determine the percent homology of two amino acid sequences or of two nucleic acids, the sequences are aligned for optimal comparison purposes (e g., gaps can be introduced in the sequence of a first amino acid or nucleic acid sequence for optimal alignment with a second amino or nucleic acid sequence). The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are homologous at that position (i.e., as used herein amino acid or nucleic acid “homology” is equivalent to amino acid or nucleic acid “identity”).

[0101] The nucleic acid sequence homology may be determined as the degree of identity between two sequences. The homology may be determined using computer programs known in the art, such as GAP software provided in the GCG program package. See, Needleman and Wunsch, 1970. J Mol Biol 48: 443-453. Using GCG GAP software with the following settings for nucleic acid sequence comparison: GAP creation penalty of 5.0 and GAP extension penalty of 0.3, the coding region of the analogous nucleic acid sequences referred to above exhibits a degree of identity preferably of at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%, with the CDS (encoding) part of the DNA sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78.

[0102] The term “sequence identity” refers to the degree to which two polynucleotide or polypeptide sequences are identical on a residue-by-residue basis over a particular region of comparison. The term “percentage of sequence identity” is calculated by comparing two optimally aligned sequences over that region of comparison, determining the number of positions at which the identical nucleic acid base (eg., A, T, C, G, U, or I, in the case of nucleic acids) occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the region of comparison (i e., the window size), and multiplying the result by 100 to yield the percentage of sequence identity. The term “substantial identity” as used herein denotes a characteristic of a polynucleotide sequence, wherein the polynucleotide comprises a sequence that has at least 80 percent sequence identity, preferably at least 85 percent identity and often 90 to 95 percent sequence identity, more usually at least 99 percent sequence identity as compared to a reference sequence over a comparison region.

[0103] Chimeric and Fusion Proteins

[0104] The invention also provides NOVX chimeric or fusion proteins. As used herein, a NOVX “chimeric protein” or “fusion protein” comprises a NOVX polypeptide operatively-linked to a non-NOVX polypeptide. An “NOVX polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a NOVX protein of SEQ ID NO:2n, wherein n is an integer between 1 and 78, whereas a “non-NOVX polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a protein that is not substantially homologous to the NOVX protein, e.g., a protein that is different from the NOVX protein and that is derived from the same or a different organism. Within a NOVX fusion protein the NOVX polypeptide can correspond to all or a portion of a NOVX protein. In one embodiment, a NOVX fusion protein comprises at least one biologically-active portion of a NOVX protein. In another embodiment, a NOVX fusion protein comprises at least two biologically-active portions of a NOVX protein. In yet another embodiment, a NOVX fusion protein comprises at least three biologically-active portions of a NOVX protein. Within the fusion protein, the term “operatively-linked” is intended to indicate that the NOVX polypeptide and the non-NOVX polypeptide are fused in-frame with one another. The non-NOVX polypeptide can be fused to the N-terminus or C-terminus of the NOVX polypeptide.

[0105] In one embodiment, the fusion protein is a GST-NOVX fusion protein in which the NOVX sequences are fused to the C-terminus of the GST (glutathione S-transferase) sequences. Such fusion proteins can facilitate the purification of recombinant NOVX polypeptides.

[0106] In another embodiment, the fusion protein is a NOVX protein containing a heterologous signal sequence at its N-terminus. In certain host cells (e.g., mammalian host cells), expression and/or secretion of NOVX can be increased through use of a heterologous signal sequence.

[0107] In yet another embodiment, the fusion protein is a NOVX-immunoglobulin fusion protein in which the NOVX sequences are fused to sequences derived from a member of the immunoglobulin protein family. The NOVX-immunoglobulin fusion proteins of the invention can be incorporated into pharmaceutical compositions and administered to a subject to inhibit an interaction between a NOVX ligand and a NOVX protein on the surface of a cell, to thereby suppress NOVX-mediated signal transduction in vivo. The NOVX-immunoglobulin fusion proteins can be used to affect the bioavailability of a NOVX cognate ligand. Inhibition of the NOVX ligand/NOVX interaction may be useful therapeutically for both the treatment of proliferative and differentiative disorders, as well as modulating (e g promoting or inhibiting) cell survival. Moreover, the NOVX-immunoglobulin fusion proteins of the invention can be used as immunogens to produce anti-NOVX antibodies in a subject, to purify NOVX ligands, and in screening assays to identify molecules that inhibit the interaction of NOVX with a NOVX ligand.

[0108] A NOVX chimeric or fusion protein of the invention can be produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques, e.g, by employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers that give rise to complementary overhangs between two consecutive gene fragments that can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, e.g., Ausubel, et al. (eds.) Current Protocols in Molecular Biology, John Wiley & Sons, 1992). Moreover, many expression vectors are commercially available that already encode a fusion moiety (e.g., a GST polypeptide). A NOVX-encoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the NOVX protein.

[0109] NOVX Agonists and Antagonists

[0110] The invention also pertains to variants of the NOVX proteins that function as either NOVX agonists (i.e., mimetics) or as NOVX antagonists. Variants of the NOVX protein can be generated by mutagenesis (e.g., discrete point mutation or truncation of the NOVX protein). An agonist of the NOVX protein can retain substantially the same, or a subset of, the biological activities of the naturally occurring form of the NOVX protein. An antagonist of the NOVX protein can inhibit one or more of the activities of the naturally occurring form of the NOVX protein by, for example, competitively binding to a downstream or upstream member of a cellular signaling cascade which includes the NOVX protein. Thus, specific biological effects can be elicited by treatment with a variant of limited function. In one embodiment, treatment of a subject with a variant having a subset of the biological activities of the naturally occurring form of the protein has fewer side effects in a subject relative to treatment with the naturally occurring form of the NOVX proteins.

[0111] Variants of the NOVX proteins that function as either NOVX agonists (i.e., mimetics) or as NOVX antagonists can be identified by screening combinatorial libraries of mutants (e.g., truncation mutants) of the NOVX proteins for NOVX protein agonist or antagonist activity. In one embodiment, a variegated library of NOVX variants is generated by combinatorial mutagenesis at the nucleic acid level and is encoded by a variegated gene library. A variegated library of NOVX variants can be produced by, for example, enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences such that a degenerate set of potential NOVX sequences is expressible as individual polypeptides, or alternatively, as a set of larger fusion proteins (e g, for phage display) containing the set of NOVX sequences therein. There are a variety of methods which can be used to produce libraries of potential NOVX variants from a degenerate oligonucleotide sequence. Chemical synthesis of a degenerate gene sequence can be performed in an automatic DNA synthesizer, and the synthetic gene then ligated into an appropriate expression vector. Use of a degenerate set of genes allows for the provision, in one mixture, of all of the sequences encoding the desired set of potential NOVX sequences. Methods for synthesizing degenerate oligonucleotides are well-known within the art. See, e.g., Narang, 1983. Tetrahedron 39: 3; Itakura, et al., 1984. Annu Rev Biochem. 53: 323; Itakura, et al., 1984. Science 198: 1056; Ike, et al., 1983. Nucl. Acids Res 11: 477.

[0112] Polypeptide Libraries

[0113] In addition, libraries of fragments of the NOVX protein coding sequences can be used to generate a variegated population of NOVX fragments for screening and subsequent selection of variants of a NOVX protein. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of a NOVX coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double-stranded DNA that can include sense/antisense pairs from different nicked products, removing single stranded portions from reformed duplexes by treatment with S1 nuclease, and ligating the resulting fragment library into an expression vector. By this method, expression libraries can be derived which encodes N-terminal and internal fragments of various sizes of the NOVX proteins.

[0114] Various techniques are known in the art for screening gene products of combinatorial libraries made by point mutations or truncation, and for screening cDNA libraries for gene products having a selected property. Such techniques are adaptable for rapid screening of the gene libraries generated by the combinatorial mutagenesis of NOVX proteins. The most widely used techniques, which are amenable to high throughput analysis, for screening large gene libraries typically include cloning the gene library into replicable expression vectors, transforming appropriate cells with the resulting library of vectors, and expressing the combinatorial genes under conditions in which detection of a desired activity facilitates isolation of the vector encoding the gene whose product was detected. Recursive ensemble mutagenesis (REM), a new technique that enhances the frequency of functional mutants in the libraries, can be used in combination with the screening assays to identify NOVX variants. See, e g., Arkin and Yourvan, 1992. Proc. Natl. Acad. Sci. USA 89: 7811-7815; Delgrave, et al., 1993. Protein Engineering 6:327-331.

[0115] Anti-NOVX Antibodies

[0116] Included in the invention are antibodies to NOVX proteins, or fragments of NOVX proteins. The term “antibody” as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin (Ig) molecules, i.e., molecules that contain an antigen binding site that specifically binds (immunoreacts with) an antigen. Such antibodies include, but are not limited to, polyclonal, monoclonal, chimeric, single chain, Fab, Fab′ and F(ab′)2 fragments, and an Fab expression library. In general, antibody molecules obtained from humans relates to any of the classes IgG, IgM, IgA, IgE and IgD, which differ from one another by the nature of the heavy chain present in the molecule. Certain classes have subclasses as well, such as IgG1, IgG2, and others. Furthermore, in humans, the light chain may be a kappa chain or a lambda chain. Reference herein to antibodies includes a reference to all such classes, subclasses and types of human antibody species.

[0117] An isolated protein of the invention intended to serve as an antigen, or a portion or fragment thereof, can be used as an immunogen to generate antibodies that immunospecifically bind the antigen, using standard techniques for polyclonal and monoclonal antibody preparation. The full-length protein can be used or, alternatively, the invention provides antigenic peptide fragments of the antigen for use as immunogens. An antigenic peptide fragment comprises at least 6 amino acid residues of the amino acid sequence of the full length protein, such as an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 78, and encompasses an epitope thereof such that an antibody raised against the peptide forms a specific immune complex with the full length protein or with any fragment that contains the epitope. Preferably, the antigenic peptide comprises at least 10 amino acid residues, or at least 15 amino acid residues, or at least 20 amino acid residues, or at least 30 amino acid residues. Preferred epitopes encompassed by the antigenic peptide are regions of the protein that are located on its surface; commonly these are hydrophilic regions.

[0118] In certain embodiments of the invention, at least one epitope encompassed by the antigenic peptide is a region of NOVX that is located on the surface of the protein, e.g., a hydrophilic region. A hydrophobicity analysis of the human NOVX protein sequence will indicate which regions of a NOVX polypeptide are particularly hydrophilic and, therefore, are likely to encode surface residues useful for targeting antibody production. As a means for targeting antibody production, hydropathy plots showing regions of hydrophilicity and hydrophobicity may be generated by any method well known in the art, including, for example, the Kyte Doolittle or the Hopp Woods methods, either with or without Fourier transformation. See, e.g., Hopp and Woods, 1981, Proc. Nat Acad Sci USA 78: 3824-3828; Kyte and Doolittle 1982, J. Mol. Biol. 157: 105-142, each incorporated herein by reference in their entirety. Antibodies that are specific for one or more domains within an antigenic protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.

[0119] The term “epitope” includes any protein determinant capable of specific binding to an immunoglobulin or T-cell receptor. Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics. A NOVX polypeptide or a fragment thereof comprises at least one antigenic epitope. An anti-NOVX antibody of the present invention is said to specifically bind to antigen NOVX when the equilibrium binding constant (KD) is ≦1 μM, preferably ≦100 nM, more preferably ≦10 nM, and most preferably ≦100 pM to about 1 pM, as measured by assays such as radioligand binding assays or similar assays known to those skilled in the art.

[0120] A protein of the invention, or a derivative, fragment, analog, homolog or ortholog thereof, may be utilized as an immunogen in the generation of antibodies that immunospecifically bind these protein components.

[0121] Various procedures known within the art may be used for the production of polyclonal or monoclonal antibodies directed against a protein of the invention, or against derivatives, fragments, analogs homologs or orthologs thereof (see, for example, Antibodies: A Laboratory Manual, Harlow E, and Lane D, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., incorporated herein by reference). Some of these antibodies are discussed below.

[0122] Polyclonal Antibodies

[0123] For the production of polyclonal antibodies, various suitable host animals (e.g., rabbit, goat, mouse or other mammal) may be immunized by one or more injections with the native protein, a synthetic variant thereof, or a derivative of the foregoing. An appropriate immunogenic preparation can contain, for example, the naturally occurring immunogenic protein, a chemically synthesized polypeptide representing the immunogenic protein, or a recombinantly expressed immunogenic protein. Furthermore, the protein may be conjugated to a second protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include but are not limited to keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsil inhibitor. The preparation can further include an adjuvant. Various adjuvants used to increase the immunological response include, but are not limited to, Freund's (complete and incomplete), mineral gels (e.g., aluminum hydroxide), surface active substances (e.g., lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, dinitrophenol, etc.), adjuvants usable in humans such as Bacille Calmette-Guerin and Corynebacterium parvum, or similar immunostimulatory agents. Additional examples of adjuvants which can be employed include MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).

[0124] The polyclonal antibody molecules directed against the immunogenic protein can be isolated from the mammal (e.g., from the blood) and further purified by well known techniques, such as affinity chromatography using protein A or protein G, which provide primarily the IgG fraction of immune serum. Subsequently, or alternatively, the specific antigen which is the target of the immunoglobulin sought, or an epitope thereof, may be immobilized on a column to purify the immune specific antibody by immunoaffinity chromatography. Purification of immunoglobulins is discussed, or example, by D. Wilkinson (The Scientist, published by The Scientist, Inc., Philadelphia Pa., Vol. 14, No. 8 (Apr. 17, 2000), pp. 25-28).

[0125] Monoclonal Antibodies

[0126] The term “monoclonal antibody” (MAb) or “monoclonal antibody composition”, as used herein, refers to a population of antibody molecules that contain only one molecular species of antibody molecule consisting of a unique light chain gene product and a unique heavy chain gene product. In particular, the complementarity determining regions (CDRs) of the monoclonal antibody are identical in all the molecules of the population. MAbs thus contain an antigen binding site capable of immunoreacting with a particular epitope of the antigen characterized by a unique binding affinity for it.

[0127] Monoclonal antibodies can be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature, 256:495 (1975). In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes can be immunized in vitro.

[0128] The immunizing agent will typically include the protein antigen, a fragment thereof or a fusion protein thereof. Generally, either peripheral blood lymphocytes are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice, Academic Press, (1986) pp. 59-103). Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells can be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (“HAT medium”), which substances prevent the growth of HGPRT-deficient cells.

[0129] Preferred immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More preferred immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, Calif. and the American Type Culture Collection, Manassas, Va. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, J. Immunol., 133:3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63).

[0130] The culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the antigen. Preferably, the binding specificity of monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA). Such techniques and assays are known in the art. The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem., 107:220 (1980). It is an objective, especially important in therapeutic applications of monoclonal antibodies, to identify antibodies having a high degree of specificity and a high binding affinity for the target antigen.

[0131] After the desired hybridoma cells are identified, the clones can be subcloned by limiting dilution procedures and grown by standard methods (Goding,1986). Suitable culture media for this purpose include, for example, Dulbecco's Modified Eagle's Medium and RPMI-1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal.

[0132] The monoclonal antibodies secreted by the subclones can be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.

[0133] The monoclonal antibodies can also be made by recombinant DNA methods, such as those described in U.S. Pat. No. 4,816,567. DNA encoding the monoclonal antibodies of the invention can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). The hybridoma cells of the invention serve as a preferred source of such DNA. Once isolated, the DNA can be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA also can be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences (U.S. Pat. No. 4,816,567; Morrison, Nature 368, 812-13 (1994)) or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. Such a non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the invention, or can be substituted for the variable domains of one antigen-combining site of an antibody of the invention to create a chimeric bivalent antibody.

[0134] Humanized Antibodies

[0135] The antibodies directed against the protein antigens of the invention can further comprise humanized antibodies or human antibodies. These antibodies are suitable for administration to humans without engendering an immune response by the human against the administered immunoglobulin. Humanized forms of antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab′, F(ab′)2 or other antigen-binding subsequences of antibodies) that are principally comprised of the sequence of a human immunoglobulin, and contain minimal sequence derived from a non-human immunoglobulin. Humanization can be performed following the method of Winter and co-workers (Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science, 239: 1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. (See also U.S. Pat. No. 5,225,539.) In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies can also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the framework regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin (Jones et al., 1986; Riechmann et al., 1988; and Presta, Curr. Op. Struct. Biol., 2:593-596 (1992)).

[0136] Human Antibodies

[0137] Fully human antibodies essentially relate to antibody molecules in which the entire sequence of both the light chain and the heavy chain, including the CDRs, arise from human genes. Such antibodies are termed “human antibodies”, or “fully human antibodies” herein. Human monoclonal antibodies can be prepared by the trioma technique; the human B-cell hybridoma technique (see Kozbor, et al., 1983 Immunol Today 4: 72) and the EBV hybridoma technique to produce human monoclonal antibodies (see Cole, et al., 1985 In: Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96). Human monoclonal antibodies may be utilized in the practice of the present invention and may be produced by using human hybridomas (see Cote, et al., 1983. Proc Natl Acad Sci USA 80: 2026-2030) or by transforming human B-cells with Epstein Barr Virus in vitro (see Cole, et al., 1985 In: Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96).

[0138] In addition, human antibodies can also be produced using additional techniques, including phage display libraries (Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991)). Similarly, human antibodies can be made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in Marks et al. (Bio/Technology 10, 779-783 (1992)); Lonberg et al. (Nature 368 856-859 (1994)); Morrison (Nature 368, 812-13 (1994)); Fishwild et al,(Nature Biotechnology 14, 845-51 (1996)); Neuberger (Nature Biotechnology 14, 826 (1996)); and Lonberg and Huszar (Intern. Rev. Immunol. 13 65-93 (1995)).

[0139] Human antibodies may additionally be produced using transgenic nonhuman animals which are modified so as to produce fully human antibodies rather than the animal's endogenous antibodies in response to challenge by an antigen. (See PCT publication WO94/02602). The endogenous genes encoding the heavy and light immunoglobulin chains in the nonhuman host have been incapacitated, and active loci encoding human heavy and light chain immunoglobulins are inserted into the host's genome. The human genes are incorporated, for example, using yeast artificial chromosomes containing the requisite human DNA segments. An animal which provides all the desired modifications is then obtained as progeny by crossbreeding intermediate transgenic animals containing fewer than the full complement of the modifications. The preferred embodiment of such a nonhuman animal is a mouse, and is termed the Xenomouse™ as disclosed in PCT publications WO 96/33735 and WO 96/34096. This animal produces B cells which secrete fully human immunoglobulins. The antibodies can be obtained directly from the animal after immunization with an immunogen of interest, as, for example, a preparation of a polyclonal antibody, or alternatively from immortalized B cells derived from the animal, such as hybridomas producing monoclonal antibodies. Additionally, the genes encoding the immunoglobulins with human variable regions can be recovered and expressed to obtain the antibodies directly, or can be further modified to obtain analogs of antibodies such as, for example, single chain Fv molecules.

[0140] An example of a method of producing a nonhuman host, exemplified as a mouse, lacking expression of an endogenous immunoglobulin heavy chain is disclosed in U.S. Pat. No. 5,939,598. It can be obtained by a method including deleting the J segment genes from at least one endogenous heavy chain locus in an embryonic stem cell to prevent rearrangement of the locus and to prevent formation of a transcript of a rearranged immunoglobulin heavy chain locus, the deletion being effected by a targeting vector containing a gene encoding a selectable marker; and producing from the embryonic stem cell a transgenic mouse whose somatic and germ cells contain the gene encoding the selectable marker.

[0141] A method for producing an antibody of interest, such as a human antibody, is disclosed in U.S. Pat. No. 5,916,771. It includes introducing an expression vector that contains a nucleotide sequence encoding a heavy chain into one mammalian host cell in culture, introducing an expression vector containing a nucleotide sequence encoding a light chain into another mammalian host cell, and fusing the two cells to form a hybrid cell. The hybrid cell expresses an antibody containing the heavy chain and the light chain.

[0142] In a further improvement on this procedure, a method for identifying a clinically relevant epitope on an immunogen, and a correlative method for selecting an antibody that binds immunospecifically to the relevant epitope with high affinity, are disclosed in PCT publication WO 99/53049.

[0143] Fab Fragments and Single Chain Antibodies

[0144] According to the invention, techniques can be adapted for the production of single-chain antibodies specific to an antigenic protein of the invention (see e g, U.S. Pat. No. 4,946,778). In addition, methods can be adapted for the construction of Fab expression libraries (see e g, Huse, et al., 1989 Science 246: 1275-1281) to allow rapid and effective identification of monoclonal Fab fragments with the desired specificity for a protein or derivatives, fragments, analogs or homologs thereof. Antibody fragments that contain the idiotypes to a protein antigen may be produced by techniques known in the art including, but not limited to: (i) an F(ab′)2 fragment produced by pepsin digestion of an antibody molecule; (ii) an Fab fragment generated by reducing the disulfide bridges of an F(ab′)2 fragment; (iii) an Fab fragment generated by the treatment of the antibody molecule with papain and a reducing agent and (iv) Fv fragments.

[0145] Bispecific Antibodies

[0146] Bispecific antibodies are monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens. In the present case, one of the binding specificities is for an antigenic protein of the invention. The second binding target is any other antigen, and advantageously is a cell-surface protein or receptor or receptor subunit.

[0147] Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello, Nature, 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829, published May 13, 1993, and in Traunecker et al., EMBO J., 10:3655-3659 (1991).

[0148] Antibody variable domains with the desired binding specificities (antibody-antigen combining sites) can be fused to immunoglobulin constant domain sequences. The fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. It is preferred to have the first heavy-chain constant region (CH1) containing the site necessary for light-chain binding present in at least one of the fusions. DNAs encoding the immunoglobulin heavy-chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. For further details of generating bispecific antibodies see, for example, Suresh et al., Methods in Enzymology, 121:210 (1986).

[0149] According to another approach described in WO 96/27011, the interface between a pair of antibody molecules can be engineered to maximize the percentage of heterodimers which are recovered from recombinant cell culture. The preferred interface comprises at least a part of the CH3 region of an antibody constant domain. In this method, one or more small amino acid side chains from the interface of the first antibody molecule are replaced with larger side chains (e.g tyrosine or tryptophan). Compensatory “cavities” of identical or similar size to the large side chain(s) are created on the interface of the second antibody molecule by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). This provides a mechanism for increasing the yield of the heterodimer over other unwanted end-products such as homodimers.

[0150] Bispecific antibodies can be prepared as full length antibodies or antibody fragments (e.g. F(ab′)2 bispecific antibodies). Techniques for generating Bispecific antibodies from antibody fragments have been described in the literature. For example, bispecific antibodies can be prepared using chemical linkage. Brennan et al., Science 229:81 (1985) describe a procedure wherein intact antibodies are proteolytically cleaved to generate F(ab′)2 fragments. These fragments are reduced in the presence of the dithiol complexing agent sodium arsenite to stabilize vicinal dithiols and prevent intermolecular disulfide formation. The Fab′ fragments generated are then converted to thionitrobenzoate (TNB) derivatives. One of the Fab′-TNB derivatives is then reconverted to the Fab′-thiol by reduction with mercaptoethylamine and is mixed with an equimolar amount of the other Fab′-TNB derivative to form the bispecific antibody. The bispecific antibodies produced can be used as agents for the selective immobilization of enzymes.

[0151] Additionally, Fab′ fragments can be directly recovered from E. coli and chemically coupled to form bispecific antibodies. Shalaby et al., J. Exp. Med. 175:217-225 (1992) describe the production of a fully humanized bispecific antibody F(ab′)2 molecule. Each Fab′ fragment was separately secreted from E. coli and subjected to directed chemical coupling in vitro to form the bispecific antibody. The bispecific antibody thus formed was able to bind to cells overexpressing the ErbB2 receptor and normal human T cells, as well as trigger the lytic activity of human cytotoxic lymphocytes against human breast tumor targets.

[0152] Various techniques for making and isolating bispecific antibody fragments directly from recombinant cell culture have also been described. For example, bispecific antibodies have been produced using leucine zippers. Kostelny et al., J. Immunol. 148(5):1547-1553 (1992). The leucine zipper peptides from the Fos and Jun proteins were linked to the Fab′ portions of two different antibodies by gene fusion. The antibody homodimers were reduced at the hinge region to form monomers and then re-oxidized to form the antibody heterodimers. This method can also be utilized for the production of antibody homodimers. The “diabody” technology described by Hollinger et al., Proc. Natl. Acad. Sci. USA 90:6444-6448 (1993) has provided an alternative mechanism for making bispecific antibody fragments. The fragments comprise a heavy-chain variable domain (VH) connected to a light-chain variable domain (VL) by a linker which is too short to allow pairing between the two domains on the same chain. Accordingly, the VH and VL domains of one fragment are forced to pair with the complementary VL and VH domains of another fragment, thereby forming two antigen-binding sites. Another strategy for making bispecific antibody fragments by the use of single-chain Fv (sFv) dimers has also been reported. See, Gruber et al., J. Immunol. 152:5368 (1994).

[0153] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).

[0154] Exemplary bispecific antibodies can bind to two different epitopes, at least one of which originates in the protein antigen of the invention. Alternatively, an anti-antigenic arm of an immunoglobulin molecule can be combined with an arm which binds to a triggering molecule on a leukocyte such as a T-cell receptor molecule (e g. CD2, CD3, CD28, or B7), or Fc receptors for IgG (FcγR), such as FcγRI (CD64), FcγRII (CD32) and FcγRIII (CD16) so as to focus cellular defense mechanisms to the cell expressing the particular antigen. Bispecific antibodies can also be used to direct cytotoxic agents to cells which express a particular antigen. These antibodies possess an antigen-binding arm and an arm which binds a cytotoxic agent or a radionuclide chelator, such as EOTUBE, DPTA, DOTA, or TETA. Another bispecific antibody of interest binds the protein antigen described herein and further binds tissue factor (TF).

[0155] Heteroconjugate Antibodies

[0156] Heteroconjugate antibodies are also within the scope of the present invention. Heteroconjugate antibodies are composed of two covalently joined antibodies. Such antibodies have, for example, been proposed to target immune system cells to unwanted cells (U.S. Pat. No. 4,676,980), and for treatment of HIV infection (WO 91/00360; WO 92/200373; EP 03089). It is contemplated that the antibodies can be prepared in vitro using known methods in synthetic protein chemistry, including those involving crosslinking agents. For example, immunotoxins can be constructed using a disulfide exchange reaction or by forming a thioether bond. Examples of suitable reagents for this purpose include iminothiolate and methyl-4-mercaptobutyrimidate and those disclosed, for example, in U.S. Pat. No. 4,676,980.

[0157] Effector Function Engineering

[0158] It can be desirable to modify the antibody of the invention with respect to effector function, so as to enhance, e.g., the effectiveness of the antibody in treating cancer. For example, cysteine residue(s) can be introduced into the Fc region, thereby allowing interchain disulfide bond formation in this region. The homodimeric antibody thus generated can have improved internalization capability and/or increased complement-mediated cell killing and antibody-dependent cellular cytotoxicity (ADCC). See Caron et al., J. Exp Med., 176: 1191-1195 (1992) and Shopes, J. Immunol., 148: 2918-2922 (1992). Homodimeric antibodies with enhanced anti-tumor activity can also be prepared using heterobifunctional cross-linkers as described in Wolff et al. Cancer Research, 53: 2560-2565 (1993). Alternatively, an antibody can be engineered that has dual Fc regions and can thereby have enhanced complement lysis and ADCC capabilities. See Stevenson et al., Anti-Cancer Drug Design, 3: 219-230 (1989).

[0159] Immunoconjugates

[0160] The invention also pertains to immunoconjugates comprising an antibody conjugated to a cytotoxic agent such as a chemotherapeutic agent, toxin (e.g, an enzymatically active toxin of bacterial, fungal, plant, or animal origin, or fragments thereof), or a radioactive isotope (i.e., a radioconjugate).

[0161] Chemotherapeutic agents useful in the generation of such immunoconjugates have been described above. Enzymatically active toxins and fragments thereof that can be used include diphtheria A chain, nonbinding active fragments of diphtheria toxin, exotoxin A chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain. alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolaca americana proteins (PAPI, PAPII, and PAP-S), momordica charantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes. A variety of radionuclides are available for the production of radioconjugated antibodies. Examples include 212Bi, 131I, 131In, 90Y, and 186Re.

[0162] Conjugates of the antibody and cytotoxic agent are made using a variety of bifunctional protein-coupling agents such as N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimidyl suberate), aldehydes (such as glutareldehyde), bis-azido compounds (such as bis(p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such as bis-(p-diazoniumbenzoyl)-ethylenediamine), disocyanates (such as tolyene 2,6-disocyanate), and bis-active fluorine compounds (such as 1,5-difluoro-2,4-dinitrobenzene). For example, a ricin immunotoxin can be prepared as described in Vitetta et al., Science, 238: 1098 (1987). Carbon-14-labeled 1-isothiocyanatobenzyl-3-methyldiethylene triaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent for conjugation of radionucleotide to the antibody. See WO94/11026.

[0163] In another embodiment, the antibody can be conjugated to a “receptor” (such streptavidin) for utilization in tumor pretargeting wherein the antibody-receptor conjugate is administered to the patient, followed by removal of unbound conjugate from the circulation using a clearing agent and then administration of a “ligand” (e.g., avidin) that is in turn conjugated to a cytotoxic agent.

[0164] Immunoliposomes

[0165] The antibodies disclosed herein can also be formulated as immunoliposomes. Liposomes containing the antibody are prepared by methods known in the art, such as described in Epstein et al., Proc. Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc. Natl Acad. Sci. USA, 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545. Liposomes with enhanced circulation time are disclosed in U.S. Pat. No. 5,013,556.

[0166] Particularly useful liposomes can be generated by the reverse-phase evaporation method with a lipid composition comprising phosphatidylcholine, cholesterol, and PEG-derivatized phosphatidylethanolamine (PEG-PE). Liposomes are extruded through filters of defined pore size to yield liposomes with the desired diameter. Fab′ fragments of the antibody of the present invention can be conjugated to the liposomes as described in Martin et al., J. Biol. Chem., 257: 286-288 (1982) via a disulfide-interchange reaction. A chemotherapeutic agent (such as Doxorubicin) is optionally contained within the liposome. See Gabizon et al., J. National Cancer Inst., 81(19): 1484 (1989).

[0167] Diagnostic Applications of Antibodies Directed Against the Proteins of the Invention

[0168] In one embodiment, methods for the screening of antibodies that possess the desired specificity include, but are not limited to, enzyme linked immunosorbent assay (ELISA) and other immunologically mediated techniques known within the art. In a specific embodiment, selection of antibodies that are specific to a particular domain of an NOVX protein is facilitated by generation of hybridomas that bind to the fragment of an NOVX protein possessing such a domain. Thus, antibodies that are specific for a desired domain within an NOVX protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.

[0169] Antibodies directed against a NOVX protein of the invention may be used in methods known within the art relating to the localization and/or quantitation of a NOVX protein (e g., for use in measuring levels of the NOVX protein within appropriate physiological samples, for use in diagnostic methods, for use in imaging the protein, and the like). In a given embodiment, antibodies specific to a NOVX protein, or derivative, fragment, analog or homolog thereof, that contain the antibody derived antigen binding domain, are utilized as pharmacologically active compounds (referred to hereinafter as “Therapeutics”).

[0170] An antibody specific for a NOVX protein of the invention (e.g., a monoclonal antibody or a polyclonal antibody) can be used to isolate a NOVX polypeptide by standard techniques, such as immunoaffinity, chromatography or immunoprecipitation. An antibody to a NOVX polypeptide can facilitate the purification of a natural NOVX antigen from cells, or of a recombinantly produced NOVX antigen expressed in host cells. Moreover, such an anti-NOVX antibody can be used to detect the antigenic NOVX protein (e g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the antigenic NOVX protein. Antibodies directed against a NOVX protein can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 125I, 131I, 35S or 3H.

[0171] Antibody Therapeutics

[0172] Antibodies of the invention, including polyclonal, monoclonal, humanized and fully human antibodies, may used as therapeutic agents. Such agents will generally be employed to treat or prevent a disease or pathology in a subject. An antibody preparation, preferably one having high specificity and high affinity for its target antigen, is administered to the subject and will generally have an effect due to its binding with the target. Such an effect may be one of two kinds, depending on the specific nature of the interaction between the given antibody molecule and the target antigen in question. In the first instance, administration of the antibody may abrogate or inhibit the binding of the target with an endogenous ligand to which it naturally binds. In this case, the antibody binds to the target and masks a binding site of the naturally occurring ligand, wherein the ligand serves as an effector molecule. Thus the receptor mediates a signal transduction pathway for which ligand is responsible.

[0173] Alternatively, the effect may be one in which the antibody elicits a physiological result by virtue of binding to an effector binding site on the target molecule. In this case the target, a receptor having an endogenous ligand which may be absent or defective in the disease or pathology, binds the antibody as a surrogate effector ligand, initiating a receptor-based signal transduction event by the receptor.

[0174] A therapeutically effective amount of an antibody of the invention relates generally to the amount needed to achieve a therapeutic objective. As noted above, this may be a binding interaction between the antibody and its target antigen that, in certain cases, interferes with the functioning of the target, and in other cases, promotes a physiological response. The amount required to be administered will furthermore depend on the binding affinity of the antibody for its specific antigen, and will also depend on the rate at which an administered antibody is depleted from the free volume other subject to which it is administered. Common ranges for therapeutically effective dosing of an antibody or antibody fragment of the invention may be, by way of nonlimiting example, from about 0.1 mg/kg body weight to about 50 mg/kg body weight. Common dosing frequencies may range, for example, from twice daily to once a week.

[0175] Pharmaceutical Compositions of Antibodies

[0176] Antibodies specifically binding a protein of the invention, as well as other molecules identified by the screening assays disclosed herein, can be administered for the treatment of various disorders in the form of pharmaceutical compositions. Principles and considerations involved in preparing such compositions, as well as guidance in the choice of components are provided, for example, in Remington: The Science And Practice Of Pharmacy 19th ed. (Alfonso R. Gennaro, et al., editors) Mack Pub. Co., Easton, Pa.: 1995; Drug Absorption Enhancement: Concepts, Possibilities, Limitations, And Trends, Harwood Academic Publishers, Langhorne, Pa., 1994; and Peptide And Protein Drug Delivery (Advances In Parenteral Sciences, Vol. 4), 1991, M. Dekker, New York.

[0177] If the antigenic protein is intracellular and whole antibodies are used as inhibitors, internalizing antibodies are preferred. However, liposomes can also be used to deliver the antibody, or an antibody fragment, into cells. Where antibody fragments are used, the smallest inhibitory fragment that specifically binds to the binding domain of the target protein is preferred. For example, based upon the variable-region sequences of an antibody, peptide molecules can be designed that retain the ability to bind the target protein sequence. Such peptides can be synthesized chemically and/or produced by recombinant DNA technology. See, e.g., Marasco et al., Proc. Natl. Acad. Sci. USA, 90: 7889-7893 (1993). The formulation herein can also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. Alternatively, or in addition, the composition can comprise an agent that enhances its function, such as, for example, a cytotoxic agent, cytokine, chemotherapeutic agent, or growth-inhibitory agent. Such molecules are suitably present in combination in amounts that are effective for the purpose intended.

[0178] The active ingredients can also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylmethacrylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles, and nanocapsules) or in macroemulsions.

[0179] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.

[0180] Sustained-release preparations can be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and γ ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT™ (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(−)-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over100 days, certain hydrogels release proteins for shorter time periods.

[0181] ELISA Assay

[0182] An agent for detecting an analyte protein is an antibody capable of binding to an analyte protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e g., Fab or F(ab)2) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e, physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. Included within the usage of the term “biological sample”, therefore, is blood and a fraction or component of blood including blood serum, blood plasma, or lymph. That is, the detection method of the invention can be used to detect an analyte mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of an analyte mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of an analyte protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of an analyte genomic DNA include Southern hybridizations. Procedures for conducting immunoassays are described, for example in “ELISA: Theory and Practice: Methods in Molecular Biology”, Vol. 42, J. R. Crowther (Ed.) Human Press, Totowa, N.J., 1995; “Immunoassay”, E. Diamandis and T. Christopoulus, Academic Press, Inc., San Diego, Calif., 1996; and “Practice and Thory of Enzyme Immunoassays”, P. Tijssen, Elsevier Science Publishers, Amsterdam, 1985. Furthermore, in vivo techniques for detection of an analyte protein include introducing into a subject a labeled anti-an analyte protein antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.

[0183] NOVX Recombinant Expression Vectors and Host Cells

[0184] Another aspect of the invention pertains to vectors, preferably expression vectors, containing a nucleic acid encoding a NOVX protein, or derivatives, fragments, analogs or homologs thereof. As used herein, the term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a “plasmid”, which refers to a circular double stranded DNA loop into which additional DNA segments can be ligated. Another type of vector is a viral vector, wherein additional DNA segments can be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e g., non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively-linked. Such vectors are referred to herein as “expression vectors”. In general, expression vectors of utility in recombinant DNA techniques are often in the form of plasmids. In the present specification, “plasmid” and “vector” can be used interchangeably as the plasmid is the most commonly used form of vector. However, the invention is intended to include such other forms of expression vectors, such as viral vectors (e.g., replication defective retroviruses, adenoviruses and adeno-associated viruses), which serve equivalent functions.

[0185] The recombinant expression vectors of the invention comprise a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, that is operatively-linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, “operably-linked” is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence(s) in a manner that allows for expression of the nucleotide sequence (e.g., in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell).

[0186] The term “regulatory sequence” is intended to includes promoters, enhancers and other expression control elements (e.g., polyadenylation signals). Such regulatory sequences are described, for example, in Goeddel, Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990). Regulatory sequences include those that direct constitutive expression of a nucleotide sequence in many types of host cell and those that direct expression of the nucleotide sequence only in certain host cells (e.g, tissue-specific regulatory sequences). It will be appreciated by those skilled in the art that the design of the expression vector can depend on such factors as the choice of the host cell to be transformed, the level of expression of protein desired, etc The expression vectors of the invention can be introduced into host cells to thereby produce proteins or peptides, including fusion proteins or peptides, encoded by nucleic acids as described herein (e.g., NOVX proteins, mutant forms of NOVX proteins, fusion proteins, etc.).

[0187] The recombinant expression vectors of the invention can be designed for expression of NOVX proteins in prokaryotic or eukaryotic cells. For example, NOVX proteins can be expressed in bacterial cells such as Escherichia coli, insect cells (using baculovirus expression vectors) yeast cells or mammalian cells. Suitable host cells are discussed further in Goeddel, Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990). Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.

[0188] Expression of proteins in prokaryotes is most often carried out in Escherichia coli with vectors containing constitutive or inducible promoters directing the expression of either fusion or non-fusion proteins. Fusion vectors add a number of amino acids to a protein encoded therein, usually to the amino terminus of the recombinant protein. Such fusion vectors typically serve three purposes: (i) to increase expression of recombinant protein; (ii) to increase the solubility of the recombinant protein; and (iii) to aid in the purification of the recombinant protein by acting as a ligand in affinity purification. Often, in fusion expression vectors, a proteolytic cleavage site is introduced at the junction of the fusion moiety and the recombinant protein to enable separation of the recombinant protein from the fusion moiety subsequent to purification of the fusion protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase. Typical fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith and Johnson, 1988. Gene 67: 31-40), pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) that fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein.

[0189] Examples of suitable inducible non-fusion E coli expression vectors include pTrc (Amrann et al., (1988) Gene 69:301-315) and pET 11d (Studier et al., Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990) 60-89).

[0190] One strategy to maximize recombinant protein expression in E. coli is to express the protein in a host bacteria with an impaired capacity to proteolytically cleave the recombinant protein. See e g., Gottesman, Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990) 119-128. Another strategy is to alter the nucleic acid sequence of the nucleic acid to be inserted into an expression vector so that the individual codons for each amino acid are those preferentially utilized in E coli (see, e.g., Wada, et al., 1992. Nucl. Acids Res. 20: 2111-2118). Such alteration of nucleic acid sequences of the invention can be carried out by standard DNA synthesis techniques.

[0191] In another embodiment, the NOVX expression vector is a yeast expression vector. Examples of vectors for expression in yeast Saccharomyces cerivisae include pYepSec1 (Baldari, et al., 1987. EMBO J. 6: 229-234), pMFa (Kurjan and Herskowitz, 1982. Cell 30: 933-943), pJRY88 (Schultz et al., 1987. Gene 54: 113-123), pYES2 (Invitrogen Corporation, San Diego, Calif.), and picZ (InVitrogen Corp, San Diego, Calif.).

[0192] Alternatively, NOVX can be expressed in insect cells using baculovirus expression vectors. Baculovirus vectors available for expression of proteins in cultured insect cells (e.g., SF9 cells) include the pAc series (Smith, et al., 1983. Mol. Cell. Biol. 3: 2156-2165) and the pVL series (Lucklow and Summers, 1989. Virology 170: 31-39).

[0193] In yet another embodiment, a nucleic acid of the invention is expressed in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, 1987. Nature 329: 840) and pMT2PC (Kaufman, et al., 1987. EMBO J. 6: 187-195). When used in mammalian cells, the expression vector's control functions are often provided by viral regulatory elements. For example, commonly used promoters are derived from polyoma, adenovirus 2, cytomegalovirus, and simian virus 40. For other suitable expression systems for both prokaryotic and eukaryotic cells see, e.g., Chapters 16 and 17 of Sambrook, et al., Molecular Cloning: A Laboratory Manual. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989.

[0194] In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid). Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert, et al., 1987. Genes Dev. 1: 268-277), lymphoid-specific promoters (Calame and Eaton, 1988. Adv. Immunol. 43: 235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989. EMBO J. 8: 729-733) and immunoglobulins (Banerji, et al., 1983. Cell 33: 729-740; Queen and Baltimore, 1983. Cell 33: 741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byrne and Ruddle, 1989. Proc. Natl. Acad. Sci. USA 86: 5473-5477), pancreas-specific promoters (Edlund, et al., 1985. Science 230: 912-916), and mammary gland-specific promoters (e g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are also encompassed, e.g., the murine hox promoters (Kessel and Gruss, 1990. Science 249: 374-379) and the α-fetoprotein promoter (Campes and Tilghman, 1989. Genes Dev. 3: 537-546).

[0195] The invention further provides a recombinant expression vector comprising a DNA molecule of the invention cloned into the expression vector in an antisense orientation. That is, the DNA molecule is operatively-linked to a regulatory sequence in a manner that allows for expression (by transcription of the DNA molecule) of an RNA molecule that is antisense to NOVX mRNA. Regulatory sequences operatively linked to a nucleic acid cloned in the antisense orientation can be chosen that direct the continuous expression of the antisense RNA molecule in a variety of cell types, for instance viral promoters and/or enhancers, or regulatory sequences can be chosen that direct constitutive, tissue specific or cell type specific expression of antisense RNA. The antisense expression vector can be in the form of a recombinant plasmid, phagemid or attenuated virus in which antisense nucleic acids are produced under the control of a high efficiency regulatory region, the activity of which can be determined by the cell type into which the vector is introduced. For a discussion of the regulation of gene expression using antisense genes see, e.g., Weintraub, et al., “Antisense RNA as a molecular tool for genetic analysis,” Reviews-Trends in Genetics, Vol. 1(1) 1986.

[0196] Another aspect of the invention pertains to host cells into which a recombinant expression vector of the invention has been introduced. The terms “host cell” and “recombinant host cell” are used interchangeably herein. It is understood that such terms refer not only to the particular subject cell but also to the progeny or potential progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein.

[0197] A host cell can be any prokaryotic or eukaryotic cell. For example, NOVX protein can be expressed in bacterial cells such as E. coli, insect cells, yeast or mammalian cells (such as Chinese hamster ovary cells (CHO) or COS cells). Other suitable host cells are known to those skilled in the art.

[0198] Vector DNA can be introduced into prokaryotic or eukaryotic cells via conventional transformation or transfection techniques. As used herein, the terms “transformation” and “transfection” are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid (e g, DNA) into a host cell, including calcium phosphate or calcium chloride co-precipitation, DEAE-dextran-mediated transfection, lipofection, or electroporation. Suitable methods for transforming or transfecting host cells can be found in Sambrook, et al. (Molecular Cloning: A Laboratory Manual. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989), and other laboratory manuals.

[0199] For stable transfection of mammalian cells, it is known that, depending upon the expression vector and transfection technique used, only a small fraction of cells may integrate the foreign DNA into their genome. In order to identify and select these integrants, a gene that encodes a selectable marker (e g., resistance to antibiotics) is generally introduced into the host cells along with the gene of interest. Various selectable markers include those that confer resistance to drugs, such as G418, hygromycin and methotrexate. Nucleic acid encoding a selectable marker can be introduced into a host cell on the same vector as that encoding NOVX or can be introduced on a separate vector. Cells stably transfected with the introduced nucleic acid can be identified by drug selection (e.g., cells that have incorporated the selectable marker gene will survive, while the other cells die).

[0200] A host cell of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (i.e., express) NOVX protein. Accordingly, the invention further provides methods for producing NOVX protein using the host cells of the invention. In one embodiment, the method comprises culturing the host cell of invention (into which a recombinant expression vector encoding NOVX protein has been introduced) in a suitable medium such that NOVX protein is produced. In another embodiment, the method further comprises isolating NOVX protein from the medium or the host cell.

[0201] Transgenic NOVX Animals

[0202] The host cells of the invention can also be used to produce non-human transgenic animals. For example, in one embodiment, a host cell of the invention is a fertilized oocyte or an embryonic stem cell into which NOVX protein-coding sequences have been introduced. Such host cells can then be used to create non-human transgenic animals in which exogenous NOVX sequences have been introduced into their genome or homologous recombinant animals in which endogenous NOVX sequences have been altered. Such animals are useful for studying the function and/or activity of NOVX protein and for identifying and/or evaluating modulators of NOVX protein activity. As used herein, a “transgenic animal” is a non-human animal, preferably a mammal, more preferably a rodent such as a rat or mouse, in which one or more of the cells of the animal includes a transgene. Other examples of transgenic animals include non-human primates, sheep, dogs, cows, goats, chickens, amphibians, etc. A transgene is exogenous DNA that is integrated into the genome of a cell from which a transgenic animal develops and that remains in the genome of the mature animal, thereby directing the expression of an encoded gene product in one or more cell types or tissues of the transgenic animal. As used herein, a “homologous recombinant animal” is a non-human animal, preferably a mammal, more preferably a mouse, in which an endogenous NOVX gene has been altered by homologous recombination between the endogenous gene and an exogenous DNA molecule introduced into a cell of the animal, e.g., an embryonic cell of the animal, prior to development of the animal.

[0203] A transgenic animal of the invention can be created by introducing NOVX-encoding nucleic acid into the male pronuclei of a fertilized oocyte (e.g., by microinjection, retroviral infection) and allowing the oocyte to develop in a pseudopregnant female foster animal. The human NOVX cDNA sequences, i.e., any one of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, can be introduced as a transgene into the genome of a non-human animal. Alternatively, a non-human homologue of the human NOVX gene, such as a mouse NOVX gene, can be isolated based on hybridization to the human NOVX cDNA (described further supra) and used as a transgene. Intronic sequences and polyadenylation signals can also be included in the transgene to increase the efficiency of expression of the transgene. A tissue-specific regulatory sequence(s) can be operably-linked to the NOVX transgene to direct expression of NOVX protein to particular cells. Methods for generating transgenic animals via embryo manipulation and microinjection, particularly animals such as mice, have become conventional in the art and are described, for example, in U.S. Pat. Nos. 4,736,866; 4,870,009; and 4,873,191; and Hogan, 1986. In: Manipulating the Mouse Embryo, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. Similar methods are used for production of other transgenic animals. A transgenic founder animal can be identified based upon the presence of the NOVX transgene in its genome and/or expression of NOVX mRNA in tissues or cells of the animals. A transgenic founder animal can then be used to breed additional animals carrying the transgene. Moreover, transgenic animals carrying a transgene-encoding NOVX protein can further be bred to other transgenic animals carrying other transgenes.

[0204] To create a homologous recombinant animal, a vector is prepared which contains at least a portion of a NOVX gene into which a deletion, addition or substitution has been introduced to thereby alter, e.g, functionally disrupt, the NOVX gene. The NOVX gene can be a human gene (e.g., the cDNA of any one of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78), but more preferably, is a non-human homologue of a human NOVX gene. For example, a mouse homologue of human NOVX gene of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, can be used to construct a homologous recombination vector suitable for altering an endogenous NOVX gene in the mouse genome. In one embodiment, the vector is designed such that, upon homologous recombination, the endogenous NOVX gene is functionally disrupted (i.e, no longer encodes a functional protein; also referred to as a “knock out” vector).

[0205] Alternatively, the vector can be designed such that, upon homologous recombination, the endogenous NOVX gene is mutated or otherwise altered but still encodes functional protein (e.g., the upstream regulatory region can be altered to thereby alter the expression of the endogenous NOVX protein). In the homologous recombination vector, the altered portion of the NOVX gene is flanked at its 5′- and 3′-termini by additional nucleic acid of the NOVX gene to allow for homologous recombination to occur between the exogenous NOVX gene carried by the vector and an endogenous NOVX gene in an embryonic stem cell. The additional flanking NOVX nucleic acid is of sufficient length for successful homologous recombination with the endogenous gene. Typically, several kilobases of flanking DNA (both at the 5′- and 3′-termini) are included in the vector. (See, e.g., Thomas, et al., 1987. Cell 51: 503 for a description of homologous recombination vectors. The vector is ten introduced into an embryonic stem cell line (e.g., by electroporation) and cells in which the introduced NOVX gene has homologously-recombined with the endogenous NOVX gene are selected. See, e.g., Li, et al., 1992. Cell 69: 915.

[0206] The selected cells are then injected into a blastocyst of an animal (e.g., a mouse) to form aggregation chimeras. See, e.g., Bradley, 1987. In: Teratocarcinomas and Embryonic Stem Cells: A Practical Approach, Robertson, ed. IRL, Oxford, pp. 113-152. A chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal and the embryo brought to term. Progeny harboring the homologously-recombined DNA in their germ cells can be used to breed animals in which all cells of the animal contain the homologously-recombined DNA by germline transmission of the transgene. Methods for constructing homologous recombination vectors and homologous recombinant animals are described further in Bradley, 1991. Curr. Opin. Biotechnol. 2: 823-829; PCT International Publication Nos.: WO 90/11354; WO 91/01140; WO 92/0968; and WO 93/04169.

[0207] In another embodiment, transgenic non-humans animals can be produced that contain selected systems that allow for regulated expression of the transgene. One example of such a system is the cre/loxP recombinase system of bacteriophage P1. For a description of the cre/loxP recombinase system, See, e.g., Lakso, et al., 1992. Proc Natl Acad Sci USA 89: 6232-6236. Another example of a recombinase system is the FLP recombinase system of Saccharomyces cerevisiae. See, O'Gorman, et al., 1991. Science 251:1351-1355. If a cre/loxP recombinase system is used to regulate expression of the transgene, animals containing transgenes encoding both the Cre recombinase and a selected protein are required. Such animals can be provided through the construction of “double” transgenic animals, e g., by mating two transgenic animals, one containing a transgene encoding a selected protein and the other containing a transgene encoding a recombinase.

[0208] Clones of the non-human transgenic animals described herein can also be produced according to the methods described in Wilmut, et al., 1997. Nature 385: 810-813. In brief, a cell (e.g., a somatic cell) from the transgenic animal can be isolated and induced to exit the growth cycle and enter G0 phase. The quiescent cell can then be fused, e.g., through the use of electrical pulses, to an enucleated oocyte from an animal of the same species from which the quiescent cell is isolated. The reconstructed oocyte is then cultured such that it develops to morula or blastocyte and then transferred to pseudopregnant female foster animal. The offspring borne of this female foster animal will be a clone of the animal from which the cell (e.g, the somatic cell) is isolated.

[0209] Pharmaceutical Compositions

[0210] The NOVX nucleic acid molecules, NOVX proteins, and anti-NOVX antibodies (also referred to herein as “active compounds”) of the invention, and derivatives, fragments, analogs and homologs thereof, can be incorporated into pharmaceutical compositions suitable for administration. Such compositions typically comprise the nucleic acid molecule, protein, or antibody and a pharmaceutically acceptable carrier. As used herein, “pharmaceutically acceptable carrier” is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. Suitable carriers are described in the most recent edition of Remington's Pharmaceutical Sciences, a standard reference text in the field, which is incorporated herein by reference. Preferred examples of such carriers or diluents include, but are not limited to, water, saline, finger's solutions, dextrose solution, and 5% human serum albumin. Liposomes and non-aqueous vehicles such as fixed oils may also be used. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, use thereof in the compositions is contemplated. Supplementary active compounds can also be incorporated into the compositions.

[0211] A pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (i.e., topical), transmucosal, and rectal administration. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid (EDTA); buffers such as acetates, citrates or phosphates, and agents for the adjustment of tonicity such as sodium chloride or dextrose. The pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic.

[0212] Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In all cases, the composition must be sterile and should be fluid to the extent that easy syringeability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as manitol, sorbitol, sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.

[0213] Sterile injectable solutions can be prepared by incorporating the active compound (e.g., a NOVX protein or anti-NOVX antibody) in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle that contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, methods of preparation are vacuum drying and freeze-drying that yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.

[0214] Oral compositions generally include an inert diluent or an edible carrier. They can be enclosed in gelatin capsules or compressed into tablets. For the purpose of oral therapeutic administration, the active compound can be incorporated with excipients and used in the form of tablets, troches, or capsules. Oral compositions can also be prepared using a fluid carrier for use as a mouthwash, wherein the compound in the fluid carrier is applied orally and swished and expectorated or swallowed. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the composition. The tablets, pills, capsules, troches and the like can contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring.

[0215] For administration by inhalation, the compounds are delivered in the form of an aerosol spray from pressured container or dispenser which contains a suitable propellant, e g, a gas such as carbon dioxide, or a nebulizer.

[0216] Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art.

[0217] The compounds can also be prepared in the form of suppositories (e.g., with conventional suppository bases such as cocoa butter and other glycerides) or retention enemas for rectal delivery.

[0218] In one embodiment, the active compounds are prepared with carriers that will protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. The materials can also be obtained commercially from Alza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions (including liposomes targeted to infected cells with monoclonal antibodies to viral antigens) can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U.S. Pat. No. 4,522,811.

[0219] It is especially advantageous to formulate oral or parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the subject to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and directly dependent on the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and the limitations inherent in the art of compounding such an active compound for the treatment of individuals.

[0220] The nucleic acid molecules of the invention can be inserted into vectors and used as gene therapy vectors. Gene therapy vectors can be delivered to a subject by, for example, intravenous injection, local administration (see, e.g., U.S. Pat. No. 5,328,470) or by stereotactic injection (see, e.g., Chen, et al., 1994. Proc Natl. Acad. Sci. USA 91: 3054-3057). The pharmaceutical preparation of the gene therapy vector can include the gene therapy vector in an acceptable diluent, or can comprise a slow release matrix in which the gene delivery vehicle is imbedded. Alternatively, where the complete gene delivery vector can be produced intact from recombinant cells, e.g, retroviral vectors, the pharmaceutical preparation can include one or more cells that produce the gene delivery system.

[0221] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

[0222] Screening and Detection Methods

[0223] The isolated nucleic acid molecules of the invention can be used to express NOVX protein (e.g, via a recombinant expression vector in a host cell in gene therapy applications), to detect NOVX mRNA (e.g., in a biological sample) or a genetic lesion in a NOVX gene, and to modulate NOVX activity, as described further, below. In addition, the NOVX proteins can be used to screen drugs or compounds that modulate the NOVX protein activity or expression as well as to treat disorders characterized by insufficient or excessive production of NOVX protein or production of NOVX protein forms that have decreased or aberrant activity compared to NOVX wild-type protein (e.g.; diabetes (regulates insulin release); obesity (binds and transport lipids); metabolic disturbances associated with obesity, the metabolic syndrome X as well as anorexia and wasting disorders associated with chronic diseases and various cancers, and infectious disease(possesses anti-microbial activity) and the various dyslipidemias. In addition, the anti-NOVX antibodies of the invention can be used to detect and isolate NOVX proteins and modulate NOVX activity. In yet a further aspect, the invention can be used in methods to influence appetite, absorption of nutrients and the disposition of metabolic substrates in both a positive and negative fashion.

[0224] The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.

[0225] Screening Assays

[0226] The invention provides a method (also referred to herein as a “screening assay”) for identifying modulators, i.e., candidate or test compounds or agents (e.g., peptides, peptidomimetics, small molecules or other drugs) that bind to NOVX proteins or have a stimulatory or inhibitory effect on, e.g., NOVX protein expression or NOVX protein activity. The invention also includes compounds identified in the screening assays described herein.

[0227] In one embodiment, the invention provides assays for screening candidate or test compounds which bind to or modulate the activity of the membrane-bound form of a NOVX protein or polypeptide or biologically-active portion thereof. The test compounds of the invention can be obtained using any of the numerous approaches in combinatorial library methods known in the art, including: biological libraries; spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; the “one-bead one-compound” library method; and synthetic library methods using affinity chromatography selection. The biological library approach is limited to peptide libraries, while the other four approaches are applicable to peptide, non-peptide oligomer or small molecule libraries of compounds. See, e.g, Lam, 1997. Anticancer Drug Design 12: 145.

[0228] A “small molecule” as used herein, is meant to refer to a composition that has a molecular weight of less than about 5 kD and most preferably less than about 4 kD. Small molecules can be, e.g, nucleic acids, peptides, polypeptides, peptidomimetics, carbohydrates, lipids or other organic or inorganic molecules. Libraries of chemical and/or biological mixtures, such as fungal, bacterial, or algal extracts, are known in the art and can be screened with any of the assays of the invention.

[0229] Examples of methods for the synthesis of molecular libraries can be found in the art, for example in: DeWitt, et al., 1993. Proc. Natl Acad. Sci. U.S.A. 90: 6909; Erb, et al., 1994. Proc. Natl. Acad. Sci. U.S.A. 91: 11422; Zuckermann, et al., 1994. J. Med. Chem. 37: 2678; Cho, et al., 1993. Science 261: 1303; Carrell, et al., 1994. Angew. Chem. Int. Ed. Engl. 33: 2059; Carell, et al., 1994. Angew. Chem. Int. Ed Engl. 33: 2061; and Gallop, et al., .1994. J. Med. Chem. 37: 1233.

[0230] Libraries of compounds may be presented in solution (e.g., Houghten, 1992. Biotechniques 13: 412-421), or on beads (Lam, 1991. Nature 354: 82-84), on chips (Fodor, 1993. Nature 364: 555-556), bacteria (Ladner, U.S. Pat. No. 5,223,409), spores (Ladner, U.S. Pat. No. 5,233,409), plasmids (Cull, et al., 1992. Proc. Natl Acad Sci USA 89: 1865-1869) or on phage (Scott and Smith, 1990. Science 249: 386-390; Devlin, 1990. Science 249: 404-406; Cwirla, et al., 1990. Proc. Natl. Acad. Sci. U.S.A. 87: 6378-6382; Felici, 1991. J. Mol. Biol. 222: 301-310; Ladner, U.S. Pat. No. 5,233,409.).

[0231] In one embodiment, an assay is a cell-based assay in which a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface is contacted with a test compound and the ability of the test compound to bind to a NOVX protein determined. The cell, for example, can of mammalian origin or a yeast cell. Determining the ability of the test compound to bind to the NOVX protein can be accomplished, for example, by coupling the test compound with a radioisotope or enzymatic label such that binding of the test compound to the NOVX protein or biologically-active portion thereof can be determined by detecting the labeled compound in a complex. For example, test compounds can be labeled with 125I, 35S, 14C, or 3H, either directly or indirectly, and the radioisotope detected by direct counting of radioemission or by scintillation counting. Alternatively, test compounds can be enzymatically-labeled with, for example, horseradish peroxidase, alkaline phosphatase, or luciferase, and the enzymatic label detected by determination of conversion of an appropriate substrate to product. In one embodiment, the assay comprises contacting a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof on the cell surface with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX protein or a biologically-active portion thereof as compared to the known compound.

[0232] In another embodiment, an assay is a cell-based assay comprising contacting a cell expressing a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface with a test compound and determining the ability of the test compound to modulate (e.g., stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX or a biologically-active portion thereof can be accomplished, for example, by determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule. As used herein, a “target molecule” is a molecule with which a NOVX protein binds or interacts in nature, for example, a molecule on the surface of a cell which expresses a NOVX interacting protein, a molecule on the surface of a second cell, a molecule in the extracellular milieu, a molecule associated with the internal surface of a cell membrane or a cytoplasmic molecule. A NOVX target molecule can be a non-NOVX molecule or a NOVX protein or polypeptide of the invention. In one embodiment, a NOVX target molecule is a component of a signal transduction pathway that facilitates transduction of an extracellular signal (e.g a signal generated by binding of a compound to a membrane-bound NOVX molecule) through the cell membrane and into the cell. The target, for example, can be a second intercellular protein that has catalytic activity or a protein that facilitates the association of downstream signaling molecules with NOVX.

[0233] Determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by one of the methods described above for determining direct binding. In one embodiment, determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by determining the activity of the target molecule. For example, the activity of the target molecule can be determined by detecting induction of a cellular second messenger of the target (i.e. intracellular Ca2+, diacylglycerol, IP3, etc), detecting catalytic/enzymatic activity of the target an appropriate substrate, detecting the induction of a reporter gene (comprising a NOVX-responsive regulatory element operatively linked to a nucleic acid encoding a detectable marker, e.g., luciferase), or detecting a cellular response, for example, cell survival, cellular differentiation, or cell proliferation.

[0234] In yet another embodiment, an assay of the invention is a cell-free assay comprising contacting a NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to bind to the NOVX protein or biologically-active portion thereof. Binding of the test compound to the NOVX protein can be determined either directly or indirectly as described above. In one such embodiment, the assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX or biologically-active portion thereof as compared to the known compound.

[0235] In still another embodiment, an assay is a cell-free assay comprising contacting NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to modulate (e.g. stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX can be accomplished, for example, by determining the ability of the NOVX protein to bind to a NOVX target molecule by one of the methods described above for determining direct binding. In an alternative embodiment, determining the ability of the test compound to modulate the activity of NOVX protein can be accomplished by determining the ability of the NOVX protein further modulate a NOVX target molecule. For example, the catalytic/enzymatic activity of the target molecule on an appropriate substrate can be determined as described, supra.

[0236] In yet another embodiment, the cell-free assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX protein to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the NOVX protein to preferentially bind to or modulate the activity of a NOVX target molecule.

[0237] The cell-free assays of the invention are amenable to use of both the soluble form or the membrane-bound form of NOVX protein. In the case of cell-free assays comprising the membrane-bound form of NOVX protein, it may be desirable to utilize a solubilizing agent such that the membrane-bound form of NOVX protein is maintained in solution. Examples of such solubilizing agents include non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, Triton® X-100, Triton® X-114, Thesit®, Isotridecypoly(ethylene glycol ether)n, N-dodecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate, 3-(3-cholamidopropyl) dimethylamminiol-1-propane sulfonate (CHAPS), or 3-(3-cholamidopropyl)dimethylamminiol-2-hydroxy-1-propane sulfonate (CHAPSO).

[0238] In more than one embodiment of the above assay methods of the invention, it may be desirable to immobilize either NOVX protein or its target molecule to facilitate separation of complexed from uncomplexed forms of one or both of the proteins, as well as to accommodate automation of the assay. Binding of a test compound to NOVX protein, or interaction of NOVX protein with a target molecule in the presence and absence of a candidate compound, can be accomplished in any vessel suitable for containing the reactants. Examples of such vessels include microtiter plates, test tubes, and micro-centrifuge tubes. In one embodiment, a fusion protein can be provided that adds a domain that allows one or both of the proteins to be bound to a matrix. For example, GST-NOVX fusion proteins or GST-target fusion proteins can be adsorbed onto glutathione sepharose beads (Sigma Chemical, St. Louis, Mo.) or glutathione derivatized microtiter plates, that are then combined with the test compound or the test compound and either the non-adsorbed target protein or NOVX protein, and the mixture is incubated under conditions conducive to complex formation (e.g., at physiological conditions for salt and pH). Following incubation, the beads or microtiter plate wells are washed to remove any unbound components, the matrix immobilized in the case of beads, complex determined either directly or indirectly, for example, as described, supra. Alternatively, the complexes can be dissociated from the matrix, and the level of NOVX protein binding or activity determined using standard techniques.

[0239] Other techniques for immobilizing proteins on matrices can also be used in the screening assays of the invention. For example, either the NOVX protein or its target molecule can be immobilized utilizing conjugation of biotin and streptavidin. Biotinylated NOVX protein or target molecules can be prepared from biotin-NHS (N-hydroxy-succinimide) using techniques well-known within the art (e.g., biotinylation kit, Pierce Chemicals, Rockford, Ill.), and immobilized in the wells of streptavidin-coated 96 well plates (Pierce Chemical). Alternatively, antibodies reactive with NOVX protein or target molecules, but which do not interfere with binding of the NOVX protein to its target molecule, can be derivatized to the wells of the plate, and unbound target or NOVX protein trapped in the wells by antibody conjugation. Methods for detecting such complexes, in addition to those described above for the GST-immobilized complexes, include immunodetection of complexes using antibodies reactive with the NOVX protein or target molecule, as well as enzyme-linked assays that rely on detecting an enzymatic activity associated with the NOVX protein or target molecule.

[0240] In another embodiment, modulators of NOVX protein expression are identified in a method wherein a cell is contacted with a candidate compound and the expression of NOVX mRNA or protein in the cell is determined. The level of expression of NOVX mRNA or protein in the presence of the candidate compound is compared to the level of expression of NOVX mRNA or protein in the absence of the candidate compound. The candidate compound can then be identified as a modulator of NOVX mRNA or protein expression based upon this comparison. For example, when expression of NOVX mRNA or protein is greater (i.e, statistically significantly greater) in the presence of the candidate compound than in its absence, the candidate compound is identified as a stimulator of NOVX mRNA or protein expression. Alternatively, when expression of NOVX mRNA or protein is less (statistically significantly less) in the presence of the candidate compound than in its absence, the candidate compound is identified as an inhibitor of NOVX mRNA or protein expression. The level of NOVX mRNA or protein expression in the cells can be determined by methods described herein for detecting NOVX mRNA or protein.

[0241] In yet another aspect of the invention, the NOVX proteins can be used as “bait proteins” in a two-hybrid assay or three hybrid assay (see, e.g., U.S. Pat. No. 5,283,317; Zervos, et al., 1993. Cell 72: 223-232; Madura, et al., 1993. J. Biol. Chem 268: 12046-12054; Bartel, et al., 1993. Biotechniques 14: 920-924; Iwabuchi, et al., 1993. Oncogene 8: 1693-1696; and Brent WO 94/10300), to identify other proteins that bind to or interact with NOVX (“NOVX-binding proteins” or “NOVX-bp”) and modulate NOVX activity. Such NOVX-binding proteins are also involved in the propagation of signals by the NOVX proteins as, for example, upstream or downstream elements of the NOVX pathway.

[0242] The two-hybrid system is based on the modular nature of most transcription factors, which consist of separable DNA-binding and activation domains. Briefly, the assay utilizes two different DNA constructs. In one construct, the gene that codes for NOVX is fused to a gene encoding the DNA binding domain of a known transcription factor (e.g., GAL-4). In the other construct, a DNA sequence, from a library of DNA sequences, that encodes an unidentified protein (“prey” or “sample”) is fused to a gene that codes for the activation domain of the known transcription factor. If the “bait” and the “prey” proteins are able to interact, in vivo, forming a NOVX-dependent complex, the DNA-bindinig and activation domains of the transcription factor are brought into close proximity. This proximity allows transcription of a reporter gene (e.g, LacZ) that is operably linked to a transcriptional regulatory site responsive to the transcription factor. Expression of the reporter gene can be detected and cell colonies containing the functional transcription factor can be isolated and used to obtain the cloned gene that encodes the protein which interacts with NOVX.

[0243] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.

[0244] Detection Assays

[0245] Portions or fragments of the cDNA sequences identified herein (and the corresponding complete gene sequences) can be used in numerous ways as polynucleotide reagents. By way of example, and not of limitation, these sequences can be used to: (i) map their respective genes on a chromosome; and, thus, locate gene regions associated with genetic disease; (ii) identify an individual from a minute biological sample (tissue typing); and (iii) aid in forensic identification of a biological sample. Some of these applications are described in the subsections, below.

[0246] Chromosome Mapping

[0247] Once the sequence (or a portion of the sequence) of a gene has been isolated, this sequence can be used to map the location of the gene on a chromosome. This process is called chromosome mapping. Accordingly, portions or fragments of the NOVX sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, or fragments or derivatives thereof, can be used to map the location of the NOVX genes, respectively, on a chromosome. The mapping of the NOVX sequences to chromosomes is an important first step in correlating these sequences with genes associated with disease.

[0248] Briefly, NOVX genes can be mapped to chromosomes by preparing PCR primers (preferably 15-25 bp in length) from the NOVX sequences. Computer analysis of the NOVX, sequences can be used to rapidly select primers that do not span more than one exon in the genomic DNA, thus complicating the amplification process. These primers can then be used for PCR screening of somatic cell hybrids containing individual human chromosomes. Only those hybrids containing the human gene corresponding to the NOVX sequences will yield an amplified fragment.

[0249] Somatic cell hybrids are prepared by fusing somatic cells from different mammals (e.g., human and mouse cells). As hybrids of human and mouse cells grow and divide, they gradually lose human chromosomes in random order, but retain the mouse chromosomes. By using media in which mouse cells cannot grow, because they lack a particular enzyme, but in which human cells can, the one human chromosome that contains the gene encoding the needed enzyme will be retained. By using various media, panels of hybrid cell lines can be established. Each cell line in a panel contains either a single human chromosome or a small number of human chromosomes, and a full set of mouse chromosomes, allowing easy mapping of individual genes to specific human chromosomes. See, e.g., D'Eustachio, et al., 1983. Science 220: 919-924. Somatic cell hybrids containing only fragments of human chromosomes can also be produced by using human chromosomes with transportations and deletions.

[0250] PCR mapping of somatic cell hybrids is a rapid procedure for assigning a particular sequence to a particular chromosome. Three or more sequences can be assigned per day using a single thermal cycler. Using the NOVX sequences to design oligonucleotide primers, sub-localization can be achieved with panels of fragments from specific chromosomes.

[0251] Fluorescence in situ hybridization (FISH) of a DNA sequence to a metaphase chromosomal spread can further be used to provide a precise chromosomal location in one step. Chromosome spreads can be made using cells whose division has been blocked in metaphase by a chemical like colcemid that disrupts the mitotic spindle. The chromosomes can be treated briefly with trypsin, and then stained with Giemsa. A pattern of light and dark bands develops on each chromosome, so that the chromosomes can be identified individually. The FISH technique can be used with a DNA sequence as short as 500 or 600 bases. However, clones larger than 1,000 bases have a higher likelihood of binding to a unique chromosomal location with sufficient signal intensity for simple detection. Preferably 1,000 bases, and more preferably 2,000 bases, will suffice to get good results at a reasonable amount of time. For a review of this technique, see, Verma, et al., Human Chromosomes: A Manual of Basic Techniques (Pergamon Press, New York 1988).

[0252] Reagents for chromosome mapping can be used individually to mark a single chromosome or a single site on that chromosome, or panels of reagents can be used for marking multiple sites and/or multiple chromosomes. Reagents corresponding to noncoding regions of the genes actually are preferred for mapping purposes. Coding sequences are more likely to be conserved within gene families, thus increasing the chance of cross hybridizations during chromosomal mapping.

[0253] Once a sequence has been mapped to a precise chromosomal location, the physical position of the sequence on the chromosome can be correlated with genetic map data. Such data are found, e.g., in McKusick, Mendelian Inheritance in Man, available on-line through Johns Hopkins University Welch Medical Library). The relationship between genes and disease, mapped to the same chromosomal region, can then be identified through linkage analysis (co-inheritance of physically adjacent genes), described in, e.g., Egeland, et al., 1987. Nature, 325: 783-787.

[0254] Moreover, differences in the DNA sequences between individuals affected and unaffected with a disease associated with the NOVX gene, can be determined. If a mutation is observed in some or all of the affected individuals but not in any unaffected individuals, then the mutation is likely to be the causative agent of the particular disease. Comparison of affected and unaffected individuals generally involves first looking for structural alterations in the chromosomes, such as deletions or translocations that are visible from chromosome spreads or detectable using PCR based on that DNA sequence. Ultimately, complete sequencing of genes from several individuals can be performed to confirm the presence of a mutation and to distinguish mutations from polymorphisms.

[0255] Tissue Typing

[0256] The NOVX sequences of the invention can also be used to identify individuals from minute biological samples. In this technique, an individual's genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identification. The sequences of the invention are useful as additional DNA markers for RFLP (“restriction fragment length polymorphisms,” described in U.S. Pat. No. 5,272,057).

[0257] Furthermore, the sequences of the invention can be used to provide an alternative technique that determines the actual base-by-base DNA sequence of selected portions of an individual's genome. Thus, the NOVX sequences described herein can be used to prepare two PCR primers from the 5′- and 3′-termini of the sequences. These primers can then be used to amplify an individual's DNA and subsequently sequence it.

[0258] Panels of corresponding DNA sequences from individuals, prepared in this manner, can provide unique individual identifications, as each individual will have a unique set of such DNA sequences due to allelic differences. The sequences of the invention can be used to obtain such identification sequences from individuals and from tissue. The NOVX sequences of the invention uniquely represent portions of the human genome. Allelic variation occurs to some degree in the coding regions of these sequences, and to a greater degree in the noncoding regions. It is estimated that allelic variation between individual humans occurs with a frequency of about once per each 500 bases. Much of the allelic variation is due to single nucleotide polymorphisms (SNPs), which include restriction fragment length polymorphisms (RFLPs).

[0259] Each of the sequences described herein can, to some degree, be used as a standard against which DNA from an individual can be compared for identification purposes. Because greater numbers of polymorphisms occur in the noncoding regions, fewer sequences are necessary to differentiate individuals. The noncoding sequences can comfortably provide positive individual identification with a panel of perhaps 10 to 1,000 primers that each yield a noncoding amplified sequence of 100 bases. If coding sequences, such as those of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.

[0260] Predictive Medicine

[0261] The invention also pertains to the field of predictive medicine in which diagnostic assays, prognostic assays, pharmacogenomics, and monitoring clinical trials are used for prognostic (predictive) purposes to thereby treat an individual prophylactically. Accordingly, one aspect of the invention relates to diagnostic assays for determining NOVX protein and/or nucleic acid expression as well as NOVX activity, in the context of a biological sample (e g, blood, serum, cells, tissue) to thereby determine whether an individual is afflicted with a disease or disorder, or is at risk of developing a disorder, associated with aberrant NOVX expression or activity. The disorders include metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, and hematopoietic disorders, and the various dyslipidemias, metabolic disturbances associated with obesity, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers. The invention also provides for prognostic (or predictive) assays for determining whether an individual is at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. For example, mutations in a NOVX gene can be assayed in a biological sample. Such assays can be used for prognostic or predictive purpose to thereby prophylactically treat an individual prior to the onset of a disorder characterized by or associated with NOVX protein, nucleic acid expression, or biological activity.

[0262] Another aspect of the invention provides methods for determining NOVX protein, nucleic acid expression or activity in an individual to thereby select appropriate therapeutic or prophylactic agents for that individual (referred to herein as “pharmacogenomics”). Pharmacogenomics allows for the selection of agents (e.g., drugs) for therapeutic or prophylactic treatment of an individual based on the genotype of the individual (e g., the genotype of the individual examined to determine the ability of the individual to respond to a particular agent.)

[0263] Yet another aspect of the invention pertains to monitoring the influence of agents (e.g., drugs, compounds) on the expression or activity of NOVX in clinical trials.

[0264] These and other agents are described in further detail in the following sections.

[0265] Diagnostic Assays

[0266] An exemplary method for detecting the presence or absence of NOVX in a biological sample involves obtaining a biological sample from a test subject and contacting the biological sample with a compound or an agent capable of detecting NOVX protein or nucleic acid (e.g., mRNA, genomic DNA) that encodes NOVX protein such that the presence of NOVX is detected in the biological sample. An agent for detecting NOVX mRNA or genomic DNA is a labeled nucleic acid probe capable of hybridizing to NOVX mRNA or genomic DNA. The nucleic acid probe can be, for example, a full-length NOVX nucleic acid, such as the nucleic acid of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78, or a portion thereof, such as an oligonucleotide of at least 15, 30, 50, 100, 250 or 500 nucleotides in length and sufficient to specifically hybridize under stringent conditions to NOVX mRNA or genomic DNA. Other suitable probes for use in the diagnostic assays of the invention are described herein.

[0267] An agent for detecting NOVX protein is an antibody capable of binding to NOVX protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g, Fab or F(ab′)2) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. That is, the detection method of the invention can be used to detect NOVX mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of NOVX mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of NOVX protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of NOVX genomic DNA include Southern hybridizations. Furthermore, in vivo techniques for detection of NOVX protein include introducing into a subject a labeled anti-NOVX antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.

[0268] In one embodiment, the biological sample contains protein molecules from the test subject. Alternatively, the biological sample can contain mRNA molecules from the test subject or genomic DNA molecules from the test subject. A preferred biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject.

[0269] In another embodiment, the methods further involve obtaining a control biological sample from a control subject, contacting the control sample with a compound or agent capable of detecting NOVX protein, mRNA, or genomic DNA, such that the presence of NOVX protein, mRNA or genomic DNA is detected in the biological sample, and comparing the presence of NOVX protein, mRNA or genomic DNA in the control sample with the presence of NOVX protein, mRNA or genomic DNA in the test sample.

[0270] The invention also encompasses kits for detecting the presence of NOVX in a biological sample. For example, the kit can comprise: a labeled compound or agent capable of detecting NOVX protein or mRNA in a biological sample; means for determining the amount of NOVX in the sample; and means for comparing the amount of NOVX in the sample with a standard. The compound or agent can be packaged in a suitable container. The kit can further comprise instructions for using the kit to detect NOVX protein or nucleic acid.

[0271] Prognostic Assays

[0272] The diagnostic methods described herein can furthermore be utilized to identify subjects having or at risk of developing a disease or disorder associated with aberrant NOVX expression or activity. For example, the assays described herein, such as the preceding diagnostic assays or the following assays, can be utilized to identify a subject having or at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. Alternatively, the prognostic assays can be utilized to identify a subject having or at risk for developing a disease or disorder. Thus, the invention provides a method for identifying a disease or disorder associated with aberrant NOVX expression or activity in which a test sample is obtained from a subject and NOVX protein or nucleic acid (e g., mRNA, genomic DNA) is detected, wherein the presence of NOVX protein or nucleic acid is diagnostic for a subject having or at risk of developing a disease or disorder associated with aberrant NOVX expression or activity. As used herein, a “test sample” refers to a biological sample obtained from a subject of interest. For example, a test sample can be a biological fluid (e.g., serum), cell sample, or tissue.

[0273] Furthermore, the prognostic assays described herein can be used to determine whether a subject can be administered an agent (e.g., an agonist, antagonist, peptidomimetic, protein, peptide, nucleic acid, small molecule, or other drug candidate) to treat a disease or disorder associated with aberrant NOVX expression or activity. For example, such methods can be used to determine whether a subject can be effectively treated with an agent for a disorder. Thus, the invention provides methods for determining whether a subject can be effectively treated with an agent for a disorder associated with aberrant NOVX expression or activity in which a test sample is obtained and NOVX protein or nucleic acid is detected (e g., wherein the presence of NOVX protein or nucleic acid is diagnostic for a subject that can be administered the agent to treat a disorder associated with aberrant NOVX expression or activity).

[0274] The methods of the invention can also be used to detect genetic lesions in a NOVX gene, thereby determining if a subject with the lesioned gene is at risk for a disorder characterized by aberrant cell proliferation and/or differentiation. In various embodiments, the methods include detecting, in a sample of cells from the subject, the presence or absence of a genetic lesion characterized by at least one of an alteration affecting the integrity of a gene encoding a NOVX-protein, or the misexpression of the NOVX gene. For example, such genetic lesions can be detected by ascertaining the existence of at least one of (i) a deletion of one or more nucleotides from a NOVX gene; (ii) an addition of one or more nucleotides to a NOVX gene; (iii) a substitution of one or more nucleotides of a NOVX gene, (iv) a chromosomal rearrangement of a NOVX gene; (v) an alteration in the level of a messenger RNA transcript of a NOVX gene, (vi) aberrant modification of a NOVX gene, such as of the methylation pattern of the genomic DNA, (vii) the presence of a non-wild-type splicing pattern of a messenger RNA transcript of a NOVX gene, (viii) a non-wild-type level of a NOVX protein, (ix) allelic loss of a NOVX gene, and (x) inappropriate post-translational modification of a NOVX protein. As described herein, there are a large number of assay techniques known in the art which can be used for detecting lesions in a NOVX gene. A preferred biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.

[0275] In certain embodiments, detection of the lesion involves the use of a probe/primer in a polymerase chain reaction (PCR) (see, e.g, U.S. Pat. Nos. 4,683,195 and 4,683,202), such as anchor PCR or RACE PCR, or, alternatively, in a ligation chain reaction (LCR) (see, e.g., Landegran, et al., 1988. Science 241: 1077-1080; and Nakazawa, et al., 1994. Proc. Natl Acad. Sci. USA 91: 360-364), the latter of which can be particularly useful for detecting point mutations in the NOVX-gene (see, Abravaya, et al., 1995. Nucl. Acids Res. 23: 675-682). This method can include the steps of collecting a sample of cells from a patient, isolating nucleic acid (e.g., genomic, mRNA or both) from the cells of the sample, contacting the nucleic acid sample with one or more primers that specifically hybridize to a NOVX gene under conditions such that hybridization and amplification of the NOVX gene (if present) occurs, and detecting the presence or absence of an amplification product, or detecting the size of the amplification product and comparing the length to a control sample. It is anticipated that PCR and/or LCR may be desirable to use as a preliminary amplification step in conjunction with any of the techniques used for detecting mutations described herein.

[0276] Alternative amplification methods include: self sustained sequence replication (see, Guatelli, et al., 1990. Proc. Natl. Acad. Sci. USA 87: 1874-1878), transcriptional amplification system (see, Kwoh, et al., 1989. Proc. Natl. Acad. Sci. USA 86: 1173-1177); Qβ Replicase (see, Lizardi, et al, 1988. BioTechnology 6: 1197), or any other nucleic acid amplification method, followed by the detection of the amplified molecules using techniques well known to those of skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low numbers.

[0277] In an alternative embodiment, mutations in a NOVX gene from a sample cell can be identified by alterations in restriction enzyme cleavage patterns. For example, sample and control DNA is isolated, amplified (optionally), digested with one or more restriction endonucleases, and fragment length sizes are determined by gel electrophoresis and compared. Differences in fragment length sizes between sample and control DNA indicates mutations in the sample DNA. Moreover, the use of sequence specific ribozymes (see, e.g., U.S. Pat. No. 5,493,531) can be used to score for the presence of specific mutations by development or loss of a ribozyme cleavage site.

[0278] In other embodiments, genetic mutations in NOVX can be identified by hybridizing a sample and control nucleic acids, e.g., DNA or RNA, to high-density arrays containing hundreds or thousands of oligonucleotides probes. See, e.g., Cronin, et al., 1996. Human Mutation 7: 244-255; Kozal, et al., 1996. Nat. Med. 2: 753-759. For example, genetic mutations in NOVX can be identified in two dimensional arrays containing light-generated DNA probes as described in Cronin, et al., supra. Briefly, a first hybridization array of probes can be used to scan through long stretches of DNA in a sample and control to identify base changes between the sequences by making linear arrays of sequential overlapping probes. This step allows the identification of point mutations. This is followed by a second hybridization array that allows the characterization of specific mutations by using smaller, specialized probe arrays complementary to all variants or mutations detected. Each mutation array is composed of parallel probe sets, one complementary to the wild-type gene and the other complementary to the mutant gene.

[0279] In yet another embodiment, any of a variety of sequencing reactions known in the art can be used to directly sequence the NOVX gene and detect mutations by comparing the sequence of the sample NOVX with the corresponding wild-type (control) sequence. Examples of sequencing reactions include those based on techniques developed by Maxim and Gilbert, 1977. Proc. Natl. Acad. Sci. USA 74: 560 or Sanger, 1977. Proc. Natl. Acad. Sci. USA 74: 5463. It is also contemplated that any of a variety of automated sequencing procedures can be utilized when performing the diagnostic assays (see, e.g, Naeve, et al., 1995. Biotechniques 19: 448), including sequencing by mass spectrometry (see, e.g, PCT International Publication No. WO 94/16101; Cohen, et al., 1996. Adv. Chromatography 36: 127-162; and Griffin, et al., 1993. Appl. Biochem. Biotechnol 38: 147-159).

[0280] Other methods for detecting mutations in the NOVX gene include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA or RNA/DNA heteroduplexes. See, e.g., Myers, et al., 1985. Science 230: 1242. In general, the art technique of “mismatch cleavage” starts by providing heteroduplexes of formed by hybridizing (labeled) RNA or DNA containing the wild-type NOVX sequence with potentially mutant RNA or DNA obtained from a tissue sample. The double-stranded duplexes are treated with an agent that cleaves single-stranded regions of the duplex such as which will exist due to basepair mismatches between the control and sample strands. For instance, RNA/DNA duplexes can be treated with RNase and DNA/DNA hybrids treated with S1 nuclease to enzymatically digesting the mismatched regions. In other embodiments, either DNA/DNA or RNA/DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion of the mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of mutation. See, e g., Cotton, et al., 1988. Proc. Natl. Acad. Sci. USA 85: 4397; Saleeba, et al., 1992. Methods Enzymol 217: 286-295. In an embodiment, the control DNA or RNA can be labeled for detection.

[0281] In still another embodiment, the mismatch cleavage reaction employs one or more proteins that recognize mismatched base pairs in double-stranded DNA (so called “DNA mismatch repair” enzymes) in defined systems for detecting and mapping point mutations in NOVX cDNAs obtained from samples of cells. For example, the mutY enzyme of E. coli cleaves A at G/A mismatches and the thymidine DNA glycosylase from HeLa cells cleaves T at G/T mismatches. (See, e.g., Hsu, et al., 1994. Carcinogenesis 15: 1657-1662. According to an exemplary embodiment, a probe based on a NOVX sequence, e.g., a wild-type NOVX sequence, is hybridized to a cDNA or other DNA product from a test cell(s). The duplex is treated with a DNA mismatch repair enzyme, and the cleavage products, if any, can be detected from electrophoresis protocols or the like. See, e.g, U.S. Pat. No. 5,459,039.

[0282] In other embodiments, alterations in electrophoretic mobility will be used to identify mutations in NOVX genes. For example, single strand conformation polymorphism (SSCP) may be used to detect differences in electrophoretic mobility between mutant and wild type nucleic acids. See, e g, Orita, et al., 1989. Proc. Natl. Acad. Sci. USA: 86: 2766; Cotton, 1993. Mutat. Res. 285: 125-144; Hayashi, 1992. Genet. Anal. Tech Appl 9: 73-79.Single-stranded DNA fragments of sample and control NOVX nucleic acids will be denatured and allowed to renature. The secondary structure of single-stranded nucleic acids varies according to sequence, the resulting alteration in electrophoretic mobility enables the detection of even a single base change. The DNA fragments may be labeled or detected with labeled probes. The sensitivity of the assay may be enhanced by using RNA (rather than DNA), in which the secondary structure is more sensitive to a change in sequence. In one embodiment, the subject method utilizes heteroduplex analysis to separate double stranded heteroduplex molecules on the basis of changes in electrophoretic mobility. See, e.g., Keen, et al., 1991. Trends Genet. 7: 5.

[0283] In yet another embodiment, the movement of mutant or wild-type fragments in polyacrylamide gels containing a gradient of denaturant is assayed using denaturing gradient gel electrophoresis (DGGE). See, e g., Myers, et al., 1985. Nature 313: 495. When DGGE is used as the method of analysis, DNA will be modified to insure that it does not completely denature, for example by adding a GC clamp of approximately 40 bp of high-melting GC-rich DNA by PCR. In a further embodiment, a temperature gradient is used in place of a denaturing gradient to identify differences in the mobility of control and sample DNA. See, e.g., Rosenbaum and Reissner, 1987. Biophys. Chem. 265: 12753.

[0284] Examples of other techniques for detecting point mutations include, but are not limited to, selective oligonucleotide hybridization, selective amplification, or selective primer extension. For example, oligonucleotide primers may be prepared in which the known mutation is placed centrally and then hybridized to target DNA under conditions that permit hybridization only if a perfect match is found. See, e.g, Saiki, et al., 1986. Nature 324: 163; Saiki, et al., 1989. Proc. Natl. Acad. Sci. USA 86: 6230. Such allele specific oligonucleotides are hybridized to PCR amplified target DNA or a number of different mutations when the oligonucleotides are attached to the hybridizing membrane and hybridized with labeled target DNA.

[0285] Alternatively, allele specific amplification technology that depends on selective PCR amplification may be used in conjunction with the instant invention. Oligonucleotides used as primers for specific amplification may carry the mutation of interest in the center of the molecule (so that amplification depends on differential hybridization; see, e.g., Gibbs, et al., 1989. Nucl. Acids Res 17: 2437-2448) or at the extreme 3′-terminus of one primer where, under appropriate conditions, mismatch can prevent, or reduce polymerase extension (see, e.g., Prossner, 1993. Tibtech. 11: 238). In addition it may be desirable to introduce a novel restriction site in the region of the mutation to create cleavage-based detection. (See, e.g., Gasparini, et al, 1992. Mol Cell Probes 6: 1. It is anticipated that in certain embodiments amplification may also be performed using Taq ligase for amplification. See, e.g, Barany, 1991. Proc. Natl. Acad. Sci. USA 88: 189. In such cases, ligation will occur only if there is a perfect match at the 3′-terminus of the 5′ sequence, making it possible to detect the presence of a known mutation at a specific site by looking for the presence or absence of amplification.

[0286] The methods described herein may be performed, for example, by utilizing pre-packaged diagnostic kits comprising at least one probe nucleic acid or antibody reagent described herein, which may be conveniently used, e.g., in clinical settings to diagnose patients exhibiting symptoms or family history of a disease or illness involving a NOVX gene.

[0287] Furthermore, any cell type or tissue, preferably peripheral blood leukocytes, in which NOVX is expressed may be utilized in the prognostic assays described herein. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.

[0288] Pharmacogenomics

[0289] Agents, or modulators that have a stimulatory or inhibitory effect on NOVX activity (e g., NOVX gene expression), as identified by a screening assay described herein can be administered to individuals to treat (prophylactically or therapeutically) disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.

[0290] In conjunction with such treatment, the pharmacogenomics (i.e., the study of the relationship between an individual's genotype and that individual's response to a foreign compound or drug) of the individual may be considered. Differences in metabolism of therapeutics can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration of the pharmacologically active drug. Thus, the pharmacogenomics of the individual permits the selection of effective agents (e.g, drugs) for prophylactic or therapeutic treatments based on a consideration of the individual's genotype. Such pharmacogenomics can further be used to determine appropriate dosages and therapeutic regimens. Accordingly, the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment of the individual.

[0291] Pharmacogenomics deals with clinically significant hereditary variations in the response to drugs due to altered drug disposition and abnormal action in affected persons. See e.g., Eichelbaum, 1996. Clin. Exp. Pharmacol. Physiol., 23: 983-985; Linder, 1997. Clin. Chem., 43: 254-266. In general, two types of pharmacogenetic conditions can be differentiated. Genetic conditions transmitted as a single factor altering the way drugs act on the body (altered drug action) or genetic conditions transmitted as single factors altering the way the body acts on drugs (altered drug metabolism). These pharmacogenetic conditions can occur either as rare defects or as polymorphisms. For example, glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymopathy in which the main clinical complication is hemolysis after ingestion of oxidant drugs (anti-malarials, sulfonamides, analgesics, nitrofurans) and consumption of fava beans.

[0292] As an illustrative embodiment, the activity of drug metabolizing enzymes is a major determinant of both the intensity and duration of drug action. The discovery of genetic polymorphisms of drug metabolizing enzymes (e.g., N-acetyltransferase 2 (NAT 2) and cytochrome pregnancy zone protein precursor enzymes CYP2D6 and CYP2C19) has provided an explanation as to why some patients do not obtain the expected drug effects or show exaggerated drug response and serious toxicity after taking the standard and safe dose of a drug. These polymorphisms are expressed in two phenotypes in the population, the extensive metabolizer (EM) and poor metabolizer (PM). The prevalence of PM is different among different populations. For example, the gene coding for CYP2D6 is highly polymorphic and several mutations have been identified in PM, which all lead to the absence of functional CYP2D6. Poor metabolizers of CYP2D6 and CYP2C19 quite frequently experience exaggerated drug response and side effects when they receive standard doses. If a metabolite is the active therapeutic moiety, PM show no therapeutic response, as demonstrated for the analgesic effect of codeine mediated by its CYP2D6-formed metabolite morphine. At the other extreme are the so called ultra-rapid metabolizers who do not respond to standard doses. Recently, the molecular basis of ultra-rapid metabolism has been identified to be due to CYP2D6 gene amplification.

[0293] Thus, the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment of the individual. In addition, pharmacogenetic studies can be used to apply genotyping of polymorphic alleles encoding drug-metabolizing enzymes to the identification of an individual's drug responsiveness phenotype. This knowledge, when applied to dosing or drug selection, can avoid adverse reactions or therapeutic failure and thus enhance therapeutic or prophylactic efficiency when treating a subject with a NOVX modulator, such as a modulator identified by one of the exemplary screening assays described herein.

[0294] Monitoring of Effects During Clinical Trials

[0295] Monitoring the influence of agents (e.g., drugs, compounds) on the expression or activity of NOVX (e g., the ability to modulate aberrant cell proliferation and/or differentiation) can be applied not only in basic drug screening, but also in clinical trials. For example, the effectiveness of an agent determined by a screening assay as described herein to increase NOVX gene expression, protein levels, or upregulate NOVX activity, can be monitored in clinical trails of subjects exhibiting decreased NOVX gene expression, protein levels, or downregulated NOVX activity. Alternatively, the effectiveness of an agent determined by a screening assay to decrease NOVX gene expression, protein levels, or downregulate NOVX activity, can be monitored in clinical trails of subjects exhibiting increased NOVX gene expression, protein levels, or upregulated NOVX activity. In such clinical trials, the expression or activity of NOVX and, preferably, other genes that have been implicated in, for example, a cellular proliferation or immune disorder can be used as a “read out” or markers of the immune responsiveness of a particular cell.

[0296] By way of example, and not of limitation, genes, including NOVX, that are modulated in cells by treatment with an agent (e.g., compound, drug or small molecule) that modulates NOVX activity (e g, identified in a screening assay as described herein) can be identified. Thus, to study the effect of agents on cellular proliferation disorders, for example, in a clinical trial, cells can be isolated and RNA prepared and analyzed for the levels of expression of NOVX and other genes implicated in the disorder. The levels of gene expression (i.e., a gene expression pattern) can be quantified by Northern blot analysis or RT-PCR, as described herein, or alternatively by measuring the amount of protein produced, by one of the methods as described herein, or by measuring the levels of activity of NOVX or other genes. In this manner, the gene expression pattern can serve as a marker, indicative of the physiological response of the cells to the agent. Accordingly, this response state may be determined before, and at various points during, treatment of the individual with the agent.

[0297] In one embodiment, the invention provides a method for monitoring the effectiveness of treatment of a subject with an agent (e.g., an agonist, antagonist, protein, peptide, peptidomimetic, nucleic acid, small molecule, or other drug candidate identified by the screening assays described herein) comprising the steps of (i) obtaining a pre-administration sample from a subject prior to administration of the agent; (ii) detecting the level of expression of a NOVX protein, mRNA, or genomic DNA in the preadministration sample; (iii) obtaining one or more post-administration samples from the subject; (iv) detecting the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the post-administration samples; (v) comparing the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the pre-administration sample with the NOVX protein, mRNA, or genomic DNA in the post administration sample or samples; and (vi) altering the administration of the agent to the subject accordingly. For example, increased administration of the agent may be desirable to increase the expression or activity of NOVX to higher levels than detected, i.e., to increase the effectiveness of the agent. Alternatively, decreased administration of the agent may be desirable to decrease expression or activity of NOVX to lower levels than detected, i e., to decrease the effectiveness of the agent.

[0298] Methods of Treatment

[0299] The invention provides for both prophylactic and therapeutic methods of treating a subject at risk of (or susceptible to) a disorder or having a disorder associated with aberrant NOVX expression or activity. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.

[0300] These methods of treatment will be discussed more fully, below.

[0301] Diseases and Disorders

[0302] Diseases and disorders that are characterized by increased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that antagonize (i.e., reduce or inhibit) activity. Therapeutics that antagonize activity may be administered in a therapeutic or prophylactic manner. Therapeutics that may be utilized include, but are not limited to: (i) an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof, (ii) antibodies to an aforementioned peptide; (iii) nucleic acids encoding an aforementioned peptide; (iv) administration of antisense nucleic acid and nucleic acids that are “dysfunctional” (i e, due to a heterologous insertion within the coding sequences of coding sequences to an aforementioned peptide) that are utilized to “knockout” endogenous function of an aforementioned peptide by homologous recombination (see, e.g., Capecchi, 1989. Science 244: 1288-1292); or (v) modulators (i.e., inhibitors, agonists and antagonists, including additional peptide mimetic of the invention or antibodies specific to a peptide of the invention) that alter the interaction between an aforementioned peptide and its binding partner.

[0303] Diseases and disorders that are characterized by decreased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that increase (i.e., are agonists to) activity. Therapeutics that upregulate activity may be administered in a therapeutic or prophylactic manner. Therapeutics that may be utilized include, but are not limited to, an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof; or an agonist that increases bioavailability.

[0304] Increased or decreased levels can be readily detected by quantifying peptide and/or RNA, by obtaining a patient tissue sample (e.g, from biopsy tissue) and assaying it in vitro for RNA or peptide levels, structure and/or activity of the expressed peptides (or mRNAs of an aforementioned peptide). Methods that are well-known within the art include, but are not limited to, immunoassays (e.g., by Western blot analysis, immunoprecipitation followed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, immunocytochemistry, etc) and/or hybridization assays to detect expression of mRNAs (e.g., Northern assays, dot blots, in situ hybridization, and the like).

[0305] Prophylactic Methods

[0306] In one aspect, the invention provides a method for preventing, in a subject, a disease or condition associated with an aberrant NOVX expression or activity, by administering to the subject an agent that modulates NOVX expression or at least one NOVX activity. Subjects at risk for a disease that is caused or contributed to by aberrant NOVX expression or activity can be identified by, for example, any or a combination of diagnostic or prognostic assays as described herein. Administration of a prophylactic agent can occur prior to the manifestation of symptoms characteristic of the NOVX aberrancy, such that a disease or disorder is prevented or, alternatively, delayed in its progression. Depending upon the type of NOVX aberrancy, for example, a NOVX agonist or NOVX antagonist agent can be used for treating the subject. The appropriate agent can be determined based on screening assays described herein. The prophylactic methods of the invention are further discussed in the following subsections.

[0307] Therapeutic Methods

[0308] Another aspect of the invention pertains to methods of modulating NOVX expression or activity for therapeutic purposes. The modulatory method of the invention involves contacting a cell with an agent that modulates one or more of the activities of NOVX protein activity associated with the cell. An agent that modulates NOVX protein activity can be an agent as described herein, such as a nucleic acid or a protein, a naturally-occurring cognate ligand of a NOVX protein, a peptide, a NOVX peptidomimetic, or other small molecule. In one embodiment, the agent stimulates one or more NOVX protein activity. Examples of such stimulatory agents include active NOVX protein and a nucleic acid molecule encoding NOVX that has been introduced into the cell. In another embodiment, the agent inhibits one or more NOVX protein activity. Examples of such inhibitory agents include antisense NOVX nucleic acid molecules and anti-NOVX antibodies. These modulatory methods can be performed in vitro (e.g., by culturing the cell with the agent) or, alternatively, in vivo (e g., by administering the agent to a subject). As such, the invention provides methods of treating an individual afflicted with a disease or disorder characterized by aberrant expression or activity of a NOVX protein or nucleic acid molecule. In one embodiment, the method involves administering an agent (e.g., an agent identified by a screening assay described herein), or combination of agents that modulates (e g., up-regulates or down-regulates) NOVX expression or activity. In another embodiment, the method involves administering a NOVX protein or nucleic acid molecule as therapy to compensate for reduced or aberrant NOVX expression or activity.

[0309] Stimulation of NOVX activity is desirable in situations in which NOVX is abnormally downregulated and/or in which increased NOVX activity is likely to have a beneficial effect. One example of such a situation is where a subject has a disorder characterized by aberrant cell proliferation and/or differentiation (e.g, cancer or immune associated disorders). Another example of such a situation is where the subject has a gestational disease (e.g., preclampsia).

[0310] Determination of the Biological Effect of the Therapeutic

[0311] In various embodiments of the invention, suitable in vitro or in vivo assays are performed to determine the effect of a specific Therapeutic and whether its administration is indicated for treatment of the affected tissue.

[0312] In various specific embodiments, in vitro assays may be performed with representative cells of the type(s) involved in the patient's disorder, to determine if a given Therapeutic exerts the desired effect upon the cell type(s). Compounds for use in therapy may be tested in suitable animal model systems including, but not limited to rats, mice, chicken, cows, monkeys, rabbits, and the like, prior to testing in human subjects. Similarly, for in vivo testing, any of the animal model system known in the art may be used prior to administration to human subjects.

[0313] Prophylactic and Therapeutic Uses of the Compositions of the Invention

[0314] The NOVX nucleic acids and proteins of the invention are useful in potential prophylactic and therapeutic applications implicated in a variety of disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.

[0315] As an example, a cDNA encoding the NOVX protein of the invention may be useful in gene therapy, and the protein may be useful when administered to a subject in need thereof. By way of non-limiting example, the compositions of the invention will have efficacy for treatment of patients suffering from diseases, disorders, conditions and the like, including but not limited to those listed herein.

[0316] Both the novel nucleic acid encoding the NOVX protein, and the NOVX protein of the invention, or fragments thereof, may also be useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. A further use could be as an anti-bacterial molecule (i.e., some peptides have been found to possess anti-bacterial properties). These materials are further useful in the generation of antibodies, which immunospecifically-bind to the novel substances of the invention for use in therapeutic or diagnostic methods.

[0317] The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims.

EXAMPLES

Example A

Polynucleotide and Polypeptide Sequences, and Homology Data

Example 1

[0318] The NOV1 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 1A.

TABLE 1A
NOV1 Sequence Analysis
                 SEQ ID NO: 1               |2548bp
NOV1a,           GCGCGGGCATCTGGCCAGCATGCTGCTCTGCACGGCTCGCCTGGTCGGCCTGCAGCTT
CG100073-01 DNA
Sequence         CTCATTTCCTGCTGCTGGGCCTTTGCCTGCCATAGCACGGAGTCTTCTCCTGACTTCA
                 CCCTCCCCGGAGATTACCTCCTGGCAGGCCTGTTCCCTCTCCATTCTGGCTGTCTGCA
                 GGTGAGGCACAGACCCGAGGTGACCCTGTGTGACAGGTCTTGTAGCTTCAATGAGCAT
                 GGCTACCACCTCTTCCAGGCTATGCGGCTTGGGGTTGAGGAGATAAACAACTCCACGG
                 CCCTGCTGCCCAACATCACCCTGGGGTACCAGCTGTATGATGTGTGTTCTGACTCTGC
                 CAATGTGTATGCCACGCTGAGAGTGCTCTCCCTGCCAGGGCAACACCACATAGAGCTC
                 CAAGGAGACCTTCTCCACTATTCCCCTACGGTGCTGGCAGTGATTGGGCCTGACAGCA
                 CCAACCGTGCTGCCACCACAGCCGCCCTGCTGAGCCCTTTCCTGGTGCCCATGGTAAG
                 CTATGCGGCCAGCAGCGAGACGCTCAGCGTGAAGCGGCAGTATCCCTCTTTCCTGCGC
                 ACCATCCCCAATGACAAGTACCAGGTGGAGACCATGGTGCTGCTGCTGCAGAAGTTCG
                 GGTGGACCTGGATCTCTCTGGTTGGCAGCAGTGACGACTATGGGCAGCTAGGGGTGCA
                 GGCACTGGAGAACCAGGCCACTGGTCAGGGGATCTGCATTGCTTTCAAGGACATCATG
                 CCCTTCTCTGCCCAGGTGGGCGATGAGAGGATGCAGTGCCTCATGCGCCACCTGGCCC
                 AGGCCGGGGCCACCGTCGTGGTTGTTTTTTCCAGCCGGCAGTTGGCCAGGGTGTTTTT
                 CGAGTCCGTGGTGCTGACCAACCTGACTGGCAAGGTGTGGGTCGCCTCAGAAGCCTGG
                 GCCCTCTCCAGGCACATCACTGGGGTGCCCGGGATCCAGCGCATTGGGATGGTGCTGG
                 GCGTGGCCATCCAGAAGAGGGCTGTCCCTGGCCTGAAGGCGTTTGAAGAAGCCTATGC
                 CCGGGCAGACAAGAAGGCCCCTAGGCCTTGCCACAAGGGCTCCTGGTGCAGCAGCAAT
                 CAGCTCTGCAGAGAATGCCAAGCTTTCATGGCACACACGATGCCCAAGCTCAAAGCCT
                 TCTCCATGAGTTCTGCCTACAACGCATACCGGGCTGTGTATGCGGTGGCCCATGGCCT
                 CCACCAGCTCCTGGGCTGTGCCTCTGGAGCTTGTTCCAGGGGCCGAGTCTACCCCTGG
                 CAGCTTTTGGAGCAGATCCACAAGGTGCATTTCCTTCTACACAAGGACACTGTGGCGT
                 TTAATGACAACAGAGATCCCCTCAGTAGCTATAACATAATTGCCTGGGACTGGAATGG
                 ACCCAAGTGGACCTTCACGGTCCTCGGTTCCTCCACATGGTCTCCAGTTCAGCTAAAC
                 ATAAATGAGACCAAAATCCAGTGGCACGGAAAGGACAACCAGGTGCCTAAGTCTGTGT
                 GTTCCAGCGACTGTCTTGAAGGGCACCAGCGAGTGGTTACGGGTTTCCATCACTGCTG
                 CTTTGAGTGTGTGCCCTGTGGGGCTGGGACCTTCCTCAACAAGAGTGACCTCTACAGA
                 TGCCAGCCTTGTGGGAAAGAAGAGTGGGCACCTGAGGGAAGCCAGACCTGCTTCCCGC
                 GCACTGTGGTGTTTTTGGCTTTGCGTGAGCACACCTCTTGGGTGCTGCTGGCAGCTAA
                 CACGCTGCTGCTGCTGCTGCTGCTTGGGACTGCTGGCCTGTTTGCCTGGCACCTAGAC
                 ACCCCTGTGGTGAGGTCAGCAGGGGGCCGCCTGTGCTTTCTTATGCTGGGCTCCCTGG
                 CAGCAGGTAGTGGCAGCCTCTATGGCTTCTTTGGGGAACCCACAAGGCCTGCGTGCTT
                 GCTACGCCAGGCCCTCTTTGCCCTTGGTTTCACCATCTTCCTGTCCTGCCTGACAGTT
                 CGCTCATTCCAACTAATCATCATCTTCAAGTTTTCCACCAAGGTACCTACATTCTACC
                 ACGCCTGGGTCCAAAACCACGGTGCTGGCCTGTTTGTGATGATCAGCTCAGCGGCCCA
                 GCTGCTTATCTGTCTAACTTGGCTGGTGGTGTGGACCCCACTGCCTGCTAGGGAATAC
                 CAGCGCTTCCCCCATCTGGTGATGCTTGAGTGCACAGAGACCAACTCCCTGGGCTTCA
                 TACTGGCCTTCCTCTACAATGGCCTCCTCTCCATCAGTGCCTTTGCCTGCAGCTACCT
                 GGGTAAGGACTTGCCAGAGAACTACAACGAGGCCAAATGTGTCACCTTCAGCCTGCTC
                 TTCAACTTCGTGTCCTGGATCGCCTTCTTCACCACGGCCAGCGTCTACGACGGCAAGT
                 ACCTGCCTGCGGCCAACATGATGGCTGGGCTGAGCAGCCTGAGCAGCGGCTTCGGTGG
                 GTATTTTCTGCCTAAGTGCTACGTGATCCTCTGCCGCCCAGACCTCAACAGCACAGAG
                 CACTTCCAGGCCTCCATTCAGGACTACACGAGGCGCTGCGGCTCCACCTGACCA
+TL,1            ORF Start: ATG at 20       |ORF Stop: TGA at 2543
                 SEQ ID NO: 2               |1841 aa  |MW at 93058.5 Da
NOV1a,           MLLCTARLVGLQLLISCCWAFACHSTESSPDFTLPGDYLLAGLFPLHSGCLQVRHRPE
CG100073-01
Protein Sequence VTLCDRSCSFNEHGYHLFQAMRLGVEEINNSTALLPNITLGYQLYDVCSDSANVYATL
                 RVLSLPGQHHIELQGDLLHYSPTVLAVIGPDSTNRAATTAALLSPFLVPMVSYAASSE
                 TLSVKRQYPSFLRTIPNDKYQVETMVLLLQKFGWTWISLVGSSDDYGQLGVQALENQA
                 TGQGICIAFKDIMPFSAQVGDERMQCLMRHLAQAGATVVVVFSSRQLARVFFESVVLT
                 NLTGKVWVASEAWALSRHITGVPGIQRIGMVLGVAIQKRAVPGLKAFEEAYARADKKA
                 PRPCHKGSWCSSNQLCRECQAFMAHTMPKLKAFSNSSAYNAYRAVYAVAHGLHQLLGC
                 ASGACSRGRVYPWQLLEQIHKVHFLLHKDTVAFNDNRDPLSSYNIIAWDWNGPKWTFT
                 VLGSSTWSPVQLNINETKIQWHGKDNQVPKSVCSSDCLEGHQRVVTGFHHCCFECVPC
                 GAGTFLNKSDLYRCQPCGKEEWAPEGSQTCFPRTVVFLALREHTSWVLLAANTLLLLL
                 LLGTAGLFAWHLDTPVVRSAGGRLCFLMLGSLAAGSGSLYGFFGEPTRPACLLRQALF
                 ALGFTIFLSCLTVRSFQLIIIFKFSTKVPTFYHAWVQNHGAGLFVMISSAAQLLICLT
                 WLVVWTPLPAREYQRFPHLVMLECTETNSLGFILAFLYNGLLSISAFACSYLGKDLPE
                 NYNEAKCVTFSLLFNFVSWIAFFTTASVYDGKYLPAANMMAGLSSLSSGFGGYFLPKC
                 YVILCRPDLNSTEHFQASIQDYTRRCGST

[0319] Further analysis of the NOV1a protein yielded the following properties shown in Table 1B.

TABLE 1B
Protein Sequence Properties NOV1a
PSort     0.6400 probability located in plasma membrane;
analysis: 0.4600 probability located in Golgi body; 0.3700 probability
          located in endoplasmic reticulum (membrane); 0.1000
          probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 21 and 22
analysis:

[0320] A search of the NOV1a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 1C.

TABLE 1C
Geneseq Results for NOV1a
		NOV1a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB77319	Human G-protein coupled receptor	1 . . . 841	840/841 (99%)	0.0
	SEQ ID NO 3 - Homo sapiens, 841	1 . . . 841	841/841 (99%)
	aa. [WO200198323-A2, 27 DEC. 2001]
AAE10372	Human taste receptor, hT1R1 protein -	1 . . . 841	840/841 (99%)	0.0
	Homo sapiens, 841 aa.	1 . . . 841	841/841 (99%)
	[WO200166563-A2, 13 SEP. 2001]
AAE11969	Human novel G-protein coupled	1 . . . 841	839/841 (99%)	0.0
	receptor (NGPCR) protein #1 - Homo	1 . . . 841	841/841 (99%)
	sapiens, 841 aa. [WO200172842-A2,
	04 OCT. 2001]
AAY45023	Human sensory transduction G-	64 . . . 841	765/778 (98%)	0.0
	protein coupled receptor-B3 - Homo	1 . . . 777	771/778 (98%)
	sapiens, 777 aa. [WO200006592-A1,
	10 FEB. 2000]
AAE11970	Human novel G-protein coupled	79 . . . 841	761/763 (99%)	0.0
	receptor (NGPCR) protein #2 - Homo	1 . . . 763	763/763 (99%)
	sapiens, 763 aa. [WO200172842-A2,
	04 OCT. 2001]

[0321] In a BLAST search of public sequence datbases, the NOV1a protein was found to have homology to the proteins shown in the BLASTP data in Table 1D.

TABLE 1D
Public BLASTP Results for NOV1a
		NOV1a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q8TDJ9	Gm148 form B - Homo sapiens	79 . . . 841	760/763 (99%)	0.0
	(Human), 763 aa.	1 . . . 763	761/763 (99%)
Q99PG5	Putative sweet taste receptor T1R1 -	8 . . . 841	620/834 (74%)	0.0
	Mus musculus (Mouse), 842 aa	9 . . . 842	705/834 (84%)
	(fragment).
Q9Z0R8	Putative taste receptor TR1 - Rattus	1 . . . 841	624/841 (74%)	0.0
	norvegicus (Rat), 840 aa	1 . . . 840	704/841 (83%)
	(fragment).
Q925I5	Candidate taste receptor TiRi -	8 . . . 841	618/834 (74%)	0.0
	Mus musculus (Mouse), 842 aa.	9 . . . 842	704/834 (84%)
Q923J9	Taste receptor T1R1 - Mus	8 . . . 841	617/834 (73%)	0.0
	musculus (Mouse), 842 aa.	9 . . . 842	703/834 (83%)

[0322] PFam analysis predicts that the NOV1a protein contains the domains shown in the Table 1E.

TABLE 1E
Domain Analysis of NOV1a
		Identities/
	NOV1a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
ANF_receptor	83 . . . 306	71/249 (29%)	1.7e−24
		165/249 (66%)
ANF_receptor	392 . . . 480	22/104 (21%)	0.037
		65/104 (62%)
7tm_3	566 . . . 822	85/287 (30%)	5.2e−31
		168/287 (59%)

Example 2

[0323] The NOV2 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2A.

TABLE 2A
NOV2 Sequence Analysis
	SEQ ID NO: 3	963 bp
NOV2a,	AGGATCCGCCGACATGAATCCCATTGTAGTGGTCCACGGCGGCGGAGCCGGTCCCATC
CG103679-02 DNA
Sequence	TCCAAGGATCGGAAGGAGCGAGTGCACCAGGGCATGGTCAGAGCCGCCACCGTGGGCT
	ACGGCATCCTCCGGGAGGGCGGGAGCGCCGTGGATGCCGTAGAGGGAGCTGTCGTCGC
	CCTGGAAGACGATCCCGAGTTCAACGCAGGTTGTGGGTCTGTCTTGAACACAAATGGT
	GAGGTTGAAATGGATGCTAGTATCATGGATGGAAAAGACCTGTCTGCAGGAGCAGTGT
	CCGCAGTCCAGTGTATAGCAAATCCCATTAAACTTGCTCGGCTTGTCATGGAAAAGAC
	ACCTCATTGCTTTCTGACTGACCAAGGCGCAGCGCAGTTTGCAGCAGCTATGGGGGTT
	CCAGAGATTCCTGGAGAAAAACTGGTGACAGAGAGAAACAAAAAGCGCCTGGAAAAAG
	AGAAGCATGAAAAAGGTGCTCAGAAAACAGATTGTCAAAAGAACTTGGGAACCGTGGG
	TGCTGTTGCCTTGGACTGCAAAGGGAATGTAGCCTACGCAACCTCCACAGGCGGTATC
	GTTAATAAAATGGTCGGCCGCGTTGGGGACTCACCGTGTCTAGGAGCTGGAGGTTATG
	CCGACAATGACATCGGAGCCGTCTCAACCACAGGGCATGGGGAAAGCATCCTGAAGGT
	GAACCTGGCTAGACTCACCCTGTTCCACATAGAACAAGGTAAGACGGTAGAAGAGGCT
	GCGGACCTATCGTTGGGTTATATGAAGTCAAGGGTTAAAGGTTTAGGTGGCCTCATCG
	TGGTTAGCAAAACAGGAGACTGGGTGGCAAAGTGGACCTCCACCTCCATGCCCTGGGC
	AGCCGCCAAGGACGGCAAGCTGCACTTCGGAATTGATCCTGACGATACTACTATCACC
	GACCTTCCCTAAGCCGCTGGAAGATTGTATTCCAG
	ORF Start: ATG at 14	ORF Stop: TAA at 938
	SEQ ID NO: 4	308 aa	MW at 32054.2 Da
NOV2a,	MNPIVVVHGGGAGPISKDRKERVHQGMVRAATVGYGILREGGSAVDAVEGAVVALEDD
CG103679-02
Protein Sequence	PEFNAGCGSVLNTNGEVEMDASIMDGKDLSAGAVSAVQCIANPIKLARLVMEKTPHCF
	LTDQGAAQFAAAMGVPEIPGEKLVTERNKKRLEKEKHEKGAQKTDCQKNLGTVGAVAL
	DCKGNVAYATSTGGIVNKMVGRVGDSPCLGAGGYADNDIGAVSTTGHGESILKVNLAR
	LTLFHIEQGKTVEEAADLSLGYMKSRVKGLGGLIVVSKTGDWVAKWTSTSMPWAAAKD
	GKLHFGIDPDDTTITDLP
	SEQ ID NO: 5	1304 bp
NOV2b,	ATGGAGGATGAGGCCATGAGCCAAGGATACAGGCAGCTTGTAGAAGCAAGAAAAGACA
G103679-03 DNA
Sequence	GATTCTCTTCTGGAGCTTCCCGAAGGAACTCAACCCTGCAGACCCAGTTTGAATTTCT
	GACCACCAGAACTGCGCAGAACCGTTGTGACCAGAGCGGTGGCGGGCTGAGCGGTTTC
	GAGCCGGCGTCGGGGAGCGGCGGTACCGGGCGGCTGCGGGGCTGGCTCGACCCAGCTG
	GAGGTCTCGGCGTCCGCGTCCTGCGGTGCCCTGGGGTCTCCCGAGGACCTTGTACCCG
	CGCGGTTTCCTTGGGCTGGCTTTGGACGACGCTTTCGCCTTCCTGCTGCCTAGGACCC
	GCCGACATGAATCCCATTGTAGTGGTCCACGGCGGCGGAGCCGGTCCCATCTCCAAGG
	ATCGGAAGGAGCGAGTGCACCAGGGCATGGTCAGAGCCGCCACCGTGGGCTACGGCAT
	CCTCCGGGAGGGCGGGAGCGCCGTGGATGCCGTAGAGGGAGCTGTCGTCGCCCTGGAA
	GACGATCCCGAGTTCAACGCAGGTTGTGGGTCTGTCTTGAACACAAATGGTGAGGTTG
	AAATGGATGCTAGTATCATGGATGGAAAAGACCTGTCTGCAGGAGCAGTGTCCGCAGT
	CCAGTGTATAGCAAATCCCATTAAAGTTGCTCGGCTTGTCATGGAAAAGACACCTCAT
	TGCTTTCTGACTGACCAAGGCGCAGCGCAGTTTGCAGCAGCTATGGGGGTTCCAGAGA
	TTCCTGGAGAAAAACTGGTGACAGAGAGAAACAAAAAGCGCCTGGAAAAAGAGAAGCA
	TGAAAAAGGTGCTCAGAAAACAGATTGTCAAAAGAACTTGGGAACCGTGGGTGCTGTT
	GCCTTGGACTGCAAAGGGAATGTAGCCTACGCAACCTCCACAGGCGGTATCGTTAATA
	AAATGGTCGGCCGCGTTGGGGACTCACCGTGTCTAGGAGCTGGAGGTTATGCCGACAA
	TGACATCGGAGCCGTCTCAACCACAGGGCATGGGGAAAGCATCCTGAAGGTGAACCTG
	GCTAGACTCACCCTGTTCCACATAGAACAAGGTAAGACGGTAGAAGAGGCTGCGGACC
	TATCGTTGGGTTATATGAAGTCAAGGGTTAAAGGTTTAGGTGGCCTCATCGTGGTTAG
	CAAAACAGGAGACTGGGTGGCAAAGTGGACCTCCACCTCCATGCCCTGGGCAGCCGCC
	AAGGACGGCAAGCTGCACTTCGGAATTGATCCTGACGATACTACTATCACCGACCTTC
	CCTAAGCCGCTGGAAGATTGTATTCCAG
	ORF Start: ATG at 1	ORF Stop: TAA at 1279
	SEQ ID NO: 6	426 aa	MW at 44593.1 Da
NOV2b,	MEDEAMSQGYRQLVEARKDRFSSGASRRNSTLQTQFEFLTTRTAQNRCDQSGGGLSGF
CG103679-03
Protein Sequence	EPASGSGGTGRLRGWLDPAGGLGVRVLRCPGVSRGPCTRAVSLGWLWTTLSPSCCLGP
	ADMNPIVVVHGGGAGPISKDRKERVHQGMVRAATVGYGILREGGSAVDAVEGAVVALE
	DDPEFNAGCGSVLNTNGEVEMDASIMDGKDLSAGAVSAVQCIANPIKLARLVMEKTPH
	CFLTDQGAAQFAAAMGVPEIPGEKLVTERNKKRLEKEKHEKGAQKTDCQKNLGTVGAV
	ALDCKGNVAYATSTGGIVNKMVGRVGDSPCLGAGGYADNDIGAVSTTGHGESILKVNL
	ARLTLFHIEQGKTVEEAADLSLGYMKSRVKGLGGLIVVSKTGDWVADWTSTSMPWAAA
	KDGKLHFGIDPDDTTITDLP
	SEQ ID NO: 7	988 bp
NOV2c,	CGCCGACATGAATCCCATTGTAGTCGCCGACATGAATCCCATTGTAGTGGTCCACGGC
CG103679-06 DNA
Sequence	GGCGGAGCCGGTCCCATCTCCAAGGATCGGAAGGAGCGAGTGCACCAGGGCATGGTCA
	GAGCCGCCACCGTGGGCTACGGCATCCTCCGGGAGGGCGGGAGCGCCGTGGATGCCGT
	AGAGGGAGCTGTCGTCGCCCTGGAAGACGATCCCGAGTTCAACGCAGGTTGTGGGTCT
	GTCTTGAACACAAATGGTGAGGTTGAAATGGATGCTAGTATCATGGATGGAAAAGACC
	TGTCTGCAGGAGCAGTGTCCGCAGTCCAGTGTATAGCAAATCCCATTAAACTTGCTCG
	GCTTGTCATGGAAAAGACACCTCATTGCTTTCTGACTGACCAAGGCGCAGCGCAGTTT
	GCAGCAGCTATGGGGGTTCCAGAGATTCCTGGAGAAAAACTGGTGACAGAGAGAAACA
	AAAAGCGCCTGGAAAAAGAGAAGCATGAAAAAGGTGCTCAGAAAACAGATTGTCAAAA
	AAACTTGGGAACCGTGGGTGCTGTTGCCTTGGACTGCAAAGGGAATGTAGCCTACGCA
	ACCTCCACAGGCGGTATCGTTAATAAAATGGTCGGCCGCGTTGGGGACTCACCGTGTC
	TAGGAGCTGGAGGTTATGCCGACAATGACATCGGAGCCGTCTCAACCACAGGGCATGG
	GGAAAGCATCCTGAAGGTGAACCTGGCTAGACTCACCCTGTTCCACATAGAACAAGGA
	AAGACGGTAGAAGAGGCTGCGGACCTATCGTTGGGTTATATGAAGTCAAGGGTTAAAG
	GTTTAGGTGGCCTCATCGTGGTTAGCAAAACAGGAGACTGGGTGGCAAAGTGGACCTC
	CACCTCCATGCCCTGGGCAGCCGCCAAGGACGGCAAGCTGCACTTCGGAATTGATCCT
	GACGATACTACTATCACCGACCTTCCCTAAGCCGCTGGAAGATTGTATTCCAAAGGGC
	GA
	ORF Start: ATG at 32	ORF Stop: TAA at 956
	SEQ ID NO: 8	308 aa	MW at 32054.2 Da
NOV2c,	MNPIVVVHGGGAGPISKDRKERVHQGMVRAATVGYGILREGGSAVDAVEGAVVALEDD
CG103679-06
Protein Sequence	PEFNAGCGSVLNTNGEVEMDASIMDGKDLSAGAVSAVQCIANPIKLARLVMEKTPHCF
	LTDQGAAQFAAAMGVPEIPGEKLVTERNKKRLEKEKHEKGAQKTDCQKNLGTVGAVAL
	DCKGNVAYATSTGGIVNKMVGRVGDSPCLGAGGYADNDIGAVSTTGHGESILKVNLAR
	LTLFHIEQGKTVEEAAKLSLGYMKSRVKGLGGLIVVSKTGDWVAKWTSTSMPWAAAKD
	GKLHFGIDPDDTTITDLP
	SEQ ID NO: 9	936 bp
NOV2d,	AGATCTATGAATCCCATTGTAGTGGTCCACGGCGGCGGAGCCGGTCCCATCTCCAAGG
CG103679-07 DNA
Sequence	ATCGGAAGGAGCGAGTGCACCAGGGCATGGTCAGAGCCGCCACCGTGGGCTACGGCAT
	CCTCCGGGAGGGCGGGAGCGCCGTGGATGCCGTAGAGGGAGCTGTCGTCGCCCTGGAA
	GACGATCCCGAGTTCAACGCAGGTTGTGGGTCTGTCTTGAACACAAATGGCGAGGTTG
	AAATGGATGCTAGTATCATGGATGGAAAAGACCTGTCTGCAGGAGCAGTGTCCGCAGT
	CCAGTGTATAGCAAATCCCATTAAACTTGCTCGGCTTGTCATGGAAAAGACACCTCAT
	TGCTTTCTGACTGACCAAGGCGCAGCGCAGTTTGCAGCAGCTATGGGGGTTCCAGAGA
	TTCCTGGAGAAAAACTGGTGACAGAGAGAAACAAAAAGCGCCTGGAAAAAGAGAAGCA
	TGAAAAAGGTGCTCAGAAAACAGATTGTCAAAAAAACTTGGGAACCGTGGGTGCTGTT
	GCCTTGGACTGCAAAGGGAATGTAGCCTACGCAACCTCCACAGGCGGTATCGTTAATA
	AAATGGTCGGCCGCGTTGGGGACTCACCGTGTCTAGGAGCTGGAGGTTATGCCGACAA
	TGACATCGGAGCCGTCTCAACCACAGGGCATGGGGAAAGCATCCTGAAGGTGAACCTG
	GCTAGACTCACCCTGTTCCACATAGAACAAGGAAAGACGGTAGAAGAGGCTGCGGACC
	TATCGTTGGGTTATATGAAGTCAAGGGTTAAAGGTTTAGGTGGCCTCATCGTGGTTAG
	CAAAACAGGAGACTGGGTGGCAAAGTGGACCTCCACCTCCATGCCCTGGGCAGCCGCC
	AAGGACGGCAAGCTGCACTTCGGAATTGATCCTGACGATACTACTATCACCGACCTTC
	CCCTCGAG
	ORF Start: ATG at 7	ORF Stop: at 931
	SEQ ID NO: 10	308 aa	MW at 32054.2 Da
NOV2d,	MNPIVVVHGGGAGPISKDRKERVHQGMVRAATVGYGILREGGSAVDAVEGAVVALEDD
CG103679-07
Protein Sequence	PEFNAGCGSVLNTNGEVEMDASIMDGKDLSAGAVSAVQCIANPIKLARLVMEKTPHCF
	LTDQGAAQFAAAMGVPEIPGEKLVTERNKKRLEKEKHEKGAQKTDCQKNLGTVGAVAL
	DCKGNVAYATSTGGIVNKMVGRVGDSPCLGAGGYADNDIGAVSTTGHGESILKVNLAR
	LTLFHIEQGKTVEEAADLSLGYMKSRVKGLGGLTVVSKTGDWVAKWTSTSMPWAAAKD
	GKLHFGIDPDDTTITDLP
	SEQ ID NO: 11	944 bp
NOV2e,	TCGCCCTTAGATCTATGAATCCCATTGTAGTGGTCCACGGCGGCGGAGCCGGTCCCAT
209770546 DNA
Sequence	CTCCAAGGATCGGAAGGAGCGAGTGCACCAGGGCATGGTCAGAGCCGCCACCGTGGGC
	TACGGCATCCTCCGGGAGGGCGGGAGCGCCGTGGATGCCGTAGAGGGAGCTGTCGTCG
	CCCTGGAAGACGATCCCGAGTTCAACGCAGGTTGTGGGTCTGTCTTGAACACAAATGG
	TGAGGTTGAAATGGATGCTAGTATCATGGATGGAAAAGACCTGTCTGCAGGAGCAGTG
	TCCGCAGTCCAGTGTATAGCAAATCCCATTAAACTTGCTCGGCTTGTCATGGAAAAGA
	CACCTCATTGCTTTCTGACTGACCAAGGCGCAGCGCAGTTTGCAGCAGCTATGGGGGT
	TCCAGAGATTCCTGGAGAAAAACTGGTGACAGAGAGAAACAAAAAGCGCCTGGAAAAA
	GAGAAGCATGAAAAAGGTGCTCAGAAAACAGATTGTCAAAAAAACTTGGGAACCGTGG
	GTGCTGTTGCCTTGGACTGCAAAGGGAATGTAGCCTACGCAACCTCCACAGGCGGTAT
	CGTTAATAAAATGGTCGGCCGCGTTGGGGACTCACCGTGTCTAGGAGCTGGAGGTTAT
	GCCGACAATGACATCGGAGCCGTCTCAACCACAGGGCATGGGGAAAGCATCCTGAAGG
	TGAACCTGGCTAGACTCACCCTGTTCCACATAGAACAAGGAAAGACGGTAGAAGAGGC
	TGCGGACCTATCGTTGGGTTATATGAAGTCAAGGGTTAAAGGTTTAGGTGGCCTCATC
	GTGGTTAGCAAAACAGGAGACTGGGTGGCAAAGTGGACCTCCACCTCCATGCCCTGGG
	CAGCCGCCAAGGACGGCAAGCTGCACTTCGGAATTGATCCTGACGATACTACTATCAC
	CGACCTTCCCCTCGAG
	ORF Start: at 3	ORF Stop: end of sequence
	SEQ ID NO: 12	314 aa	MW at 32724.0 Da
NOV2e,	ALRSMNPIVVVHGGGAGPISKDRKERVHQGMVRAATVGYGILREGGSAVDAVEGAVVA
209770546 Protein
Sequence	LEDDPEFNAGCGSVLNTNGEVEMDASIMDGKDLSAGAVSAVQCIANPIKLARLVMEKT
	PHCFLTDQGAAQFAAAMGVPEIPGEKLVTERNKKRLEKEKGEKGAQKTDCQKNLGTVG
	AVALDCKGNVAYATSTGGIVNKMVGRVGDSPCLGAGGYADNDIGAVSTTGHGESILKV
	NLARLTLFHIEQGKTVEEAADLSLGYMKSRVKGLGGLIVVSKTGDWVAKWTSTSMPWA
	AAKDGKLHFGIDPDDTTITDLPLE
	SEQ ID NO: 13	936 bp
NOV2f,	AGATCTATGAATCCCATTGTAGTGGTCCACGGCGGCGGAGCCGGTCCCATCTCCAAGG
209770585 DNA
Sequence	ATCGGAAGGAGCGAGTGCACCAGGGCATGGTCAGAGCCGCCACCGTGGGCTACGGCAT
	CCTCCGGGAGGGCGGGAGCGCCGTGGATGCCGTAGAGGGAGCTGTCGTCGCCCTGGAA
	GACGATCCCGAGTTCAACGCAGGTTGTGGGTCTGTCTTGAACACAAATGGTGAGGTTG
	AAATGGATGCTAGTATCATGGATGGAAAAGACCTGTCTGCAGGAGCAGTGTCCGCAGT
	CCAGTGTATAGCAAATCCCATTAAACTTGCTCGGCTTGTCATGGAAAAGACACCTCAT
	TGCTTTCTGACTGACCAAGGCGCAGCGCAGTTTGCAGCAGCTATGGGGGTTCCAGAGA
	TTCCTGGAGAAAAACTGGTGACAGAGAGAAACAAAAAGCGCCTGGAAAAAGAGAAGCA
	TGAAAAAGGTGCTCAGAAAACAGATTGTCAAAAAAACTTGGGAACCGTGGGTGCTGTT
	GCCTTGGACTGCAAAGGGAATGTAGCCTACGCAACCTCCACAGGCGGTATCGTTAATA
	AAATGGTCGGCCGCGTTGGGGACTCACCGTGTCTAGGAGCTGGAGGTTATGCCGACAA
	TGACATCGGAGCCGTCTCAACCACAGGGCATGGGGAAAGCATCCTGAAGGTGAACCTG
	GCTAGACTCACCCTGTTCCACATAGAACAAGGAAAGACGGTAGAAGAGGCTGCGGACC
	TATCGTTGGGTTATATGAAGTCAAGGGTTAAAGGTTTAGGTGGCCTCATCGTGGTTAG
	CAAAACAGGAGACTGGGTGGCAAAGTGGACCTCCACCTCCATGCCCTGGGCAGCCGCC
	AAGGACGGCAAGCTGCACTTCGGAATTGATCCTGACGATACTACTATCACCGACCTTC
	CCCTCGAG
	ORF Start: at 1	ORF Stop: end of sequence
	SEQ ID NO: 14	312 aa	MW at 32539.8 Da
NOV2f,	RSMNPIVVVHGGGAGPISKDRKERVHQGMVRAATVGYGILREGGSAVDAVEGAVVALE
209770585 Protein
Sequence	DDPEFNAGCGSVLNTNGEVEMDASIMDGKDLSAGAVSAVQCIANPIKLARLVMEKTPH
	CFLTDQGAAQFAAAMGVPEIPGEKLVTERNKKRLEKEKHEKGAQKTDCQKNLGTVGAV
	ALDCKGNVAYATSTGGIVNKMVGRVGDSPCLGAGGYADNDIGAVSTTGHGESILKVNL
	ARLTLFHIEQGKTVEEAADLSLGYMKSRVKGLGGLIVVSKTGDWVAKWTSTSMPWAAA
	KDGKLHFGIDPDDTTITDLPLE
	SEQ ID NO: 15	936 bp
NOV2g,	AGATCTATGAATCCCATTGTAGTGGTCCACGGCGGCGGAGCCGGTCCCATCTCCAAGG
209770611 DNA
Sequence	ATCGGAAGGAGCGAGTGCACCAGGGCATGGTCAGAGCCGCCACCGTGGGCTACGGCAT
	CCTCCGGGAGGGCGGGAGCGCCGTGGATGCCGTAGAGGGAGCTGTCGTCGCCCTGGAA
	GACGATCCCGAGTTCAACGCAGGTTGTGGGTCTGTCTTGAACACAAATGGTGAGGTTG
	AAATGGATGCTAGTATCATGGATGGAAAAGACCTGTCTGCAGGAGCAGTGTCCGCAGT
	CCAGTGTATAGCAAATCCCATTAAACTTGCTCGGCTTGTCATGGAAAAGACACCTCAT
	TGCTTTCTGACTGACCAAGGCGCAGCGCAGTTTGCAGCAGCTATGGGGGTTCCAGAGA
	TTCCTGGAGAAAAACTGGTGACAGAGAGAAACAAAAAGCGCCTGGAAAAAGAGAAGCA
	TGAAAAAGGTGCTCAGAAAACAGATTGTCAAAAAAATTTGGGAACCGTGGGTGCTGTT
	GCCTTGGACTGCAAAGGGAATGTAGCCTACGCAACCTCCACAGGCGGTATCGTTAATA
	AAATGGTCGGCCGCGTTGGGGACTCACCGTGTCTAGGAGCTGGAGGTTATGCCGACAA
	TGACATCGGAGCCGTCTCAACCACAGGGCATGGGGAAAGCATCCTGAAGGTGAACCTG
	GCTAGACTCACCCTGTTCCACATAGAACAAGGAAAGACGGTAGAAGAGGCTGCGGACC
	TATCGTTGGGTTATATGAAGTCAAGGGTTAAAGGTTTAGGTGGCCTCATCGTGGTTAG
	CAAAACAGGAGACTGGGTGGCAAAGTGGACCTCCACCTCCATGCCCTGGGCAGCCGCC
	AAGGACGGCAAGCTGCACTTCGGAATTGATCCTGACGATACTACTATCACCGACCTTC
	CCCTCGAG
	ORF Start: at 1	ORF Stop: end of sequence
	SEQ ID NO: 16	312 aa	MW at 32539.8 Da
NOV2g,	RSMNPIVVVHGGGAGPISKDRKERVHQGMVRAATVGYGILREGGSAVDAVEGAVVALE
209770611 Protein
Sequence	DDPEFNAGCGSVLNTNGEVEMDASIMDGKDLSAGAVSAVQCIANPIKLARLVMEKTPH
	CFLTDQGAAQFAAAMGVPEIPGEKLVTERNKKRLEKEKHEKGAQKTDCQKNLGTVGAV
	ALDCKGNVAYATSTGGIVNKMVGRVGDSPCLGAGGYADNDIGAVSTTGHGESILKVNL
	ARLTLFHIEQGKTVEEAADLSLGYMKSRVKGLGGLIVVSKTGDWVAKWTSTSMPWAAA
	KDGKLHFGIDPDDTTITDLPLE

[0324] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 2B.

TABLE 2B
Comparison of NOV2a against NOV2b through NOV2g.
Protein	NOV2a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV2b	1 . . . 308	298/308 (96%)
	119 . . . 426	298/308 (96%)
NOV2c	1 . . . 308	298/308 (96%)
	1 . . . 308	298/308 (96%)
NOV2d	1 . . . 308	298/308 (96%)
	1 . . . 308	298/308 (96%)
NOV2e	1 . . . 296	296/296 (100%)
	5 . . . 300	296/296 (100%)
NOV2f	1 . . . 296	296/296 (100%)
	3 . . . 298	296/296 (100%)
NOV2g	1 . . . 296	296/296 (100%)
	3 . . . 298	296/296 (100%)

[0325] Further analysis of the NOV2a protein yielded the following properties shown in Table 2C.

TABLE 2C
Protein Sequence Properties NOV2a
PSort     0.4500 probability located in cyctoplasm; 0.3000
analysis: probability located in microbody (peroxisome);
          0.1522 probability located in lysosome (lumen);
          0.1000 probability located in mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0326] A search of the NOV2a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 2D.

TABLE 2D
Geneseq Results for NOV2a
		NOV2a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM41584	Human polypeptide SEQ ID NO	1 . . . 308	308/308 (100%)	e−178
	6515 - Homo sapiens, 346 aa.	39 . . . 346	308/308 (100%)
	[WO200153312-A1, 26 JUL. 2001]
AAM39798	Human polypeptide SEQ ID NO	1 . . . 308	308/308 (100%)	e−178
	2943 - Homo sapiens, 308 aa.	1 . . . 308	308/308 (100%)
	[WO200153312-A1, 26 JUL. 2001]
ABG20227	Novel human diagnostic protein	1 . . . 293	273/294 (92%)	e−156
	#20218 - Homo sapiens, 338 aa.	41 . . . 334	279/294 (94%)
	[WO200175067-A2, 11 OCT. 2001]
ABG20227	Novel human diagnostic protein	1 . . . 293	273/294 (92%)	e−156
	#20218 - Homo sapiens, 338 aa.	41 . . . 334	279/294 (94%)
	[WO200175067-A2, 11 OCT. 2001]
AAG67131	Amino acid sequence of a human	1 . . . 164	164/164 (100%)	2e−90
	enzyme - Homo sapiens, 164 aa.	1 . . . 164	164/164 (100%)
	[WO200164896-A2, 07 SEP. 2001]

[0327] In a BLAST search of public sequence datbases, the NOV2a protein was found to have homology to the proteins shown in the BLASTP data in Table 2E.

TABLE 2E
Public BLASTP Results for NOV2a
		NOV2a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
AAM28434	Asparaginase-like protein - Homo	1 . . . 308	307/308 (99%)	e−177
	sapiens (Human), 308 aa.	1 . . . 308	307/308 (99%)
Q8VI04	Asparaginase-like sperm	4 . . . 308	237/305 (77%)	e−137
	autoantigen - Rattus norvegicus	27 . . . 331	268/305 (87%)
	(Rat), 333 aa.
Q9CVX3	2410004D18Rik protein - Mus	15 . . . 308	231/294 (78%)	e−133
	musculus (Mouse), 342 aa	48 . . . 341	258/294 (87%)
	(fragment).
Q9H6F7	CDNA: FLJ22316 fis, clone	77 . . . 308	232/232 (100%)	e−132
	HRC05262 (Hypothetical 24.3 kDa	1 . . . 232	232/232 (100%)
	protein) - Homo sapiens (Human),
	232 aa.
Q9BRH2	Similar to hypothetical protein	110 . . . 308	199/199 (100%)	e−113
	FLJ22316 - Homo sapiens	4 . . . 202	199/199 (100%)
	(Human), 202 aa (fragment).

[0328] PFam analysis predicts that the NOV2a protein contains the domains shown in the

TABLE 2F
Domain Analysis of NOV2a
		Identities/
	NOV2a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
Asparaginase_2	1 . . . 302	126/380 (33%)	6.4e−72
		206/380 (54%)

Example 3

[0329] The NOV3 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3A.

TABLE 3A
NOV3 Sequence Analysis
	SEQ ID NO: 17	1016 bp
NOV3a,	CTCAAAGCATTGGGCACTGATGTCTTCTGACTAATGGACCTAAGTCTCTGTACTTTCA
CG109541-01 DNA
Sequence	ATCTGTTTATTTATCCAACGAAGAGAGAGAACCACACAGTGATAAGGGAGTTTGTTTT
	CCAGGGTTTCTCCAGCTTTCATGAACACAAGCTTACCCTCTTTGTGGTATTTCTTACC
	TTGTGTCTTTTAACCCTGGCTGGCAATGTCATAATTGTGACAATTATCAGCATTGATC
	GTCACCTTCACACCCCCATGTACTTCTTTGTTAGTATGCTTTCCACTTCAGAGACTGT
	CTACACATTAGTCATTGTACCACGGATGCTCTCCAGTCTCTTAAGTCTAAGCCAACCT
	ATCTCTTTGGGTGGCTGTGCCACCCAGATGTTTTTTATTACCTTGGCCATCAACAACT
	GCTTTCTGCTCACAGCAATGGGGTATGATCGCTATGTGGCCATCTGTAACCCTTTGAG
	GTACATGATCATCATGAACAAGAAAGTGTGTGTCCAGCTGGTATGTGGGTCCTGCAGT
	GTTGGGCTGCTTGTGGCCATAGTTCAGATTTCATCTGTGTTCAGGCTGCCTTTTTGTG
	ATAAACAGGTGGCCCATTATTTCTGTGATATCCACCCAGTTATGAAACTTTCCTGTGT
	TGATACCACTCTACATGACCTAATTAATTTTGTTGTTAGTTCCCTGGTTATTGTGGTG
	CCGCTGGGTTTGGTCTTCATCTCCTACATCCTCATCATCTCTACCATCCTCAAGGTCA
	CCTCTCCTGAGGGCCGGAAAAAGGCTTTTGCAACTTGTGCCTCCCACCTCACTGTGGT
	TATCATCCACTATGGCTGTGCCTCCATTGCCTACCTCAAGCCCAAGTCAGAGAACACC
	AGGGATCAGGACCAGCTAATTTCAGTGACATACACCGTCTTTACTCCACTACTTAATC
	CTGTTGTGTACACTTTGAGGAACAAGGAGGTCAAGAATGCCCTTCACCGTGCTATTGG
	CAAAAAACCTTTTGCCTAGAATCTTCATCA
	ORF Start: ATG at 34	ORF Stop: TAG at 1003
	SEQ ID NO: 18	323 aa	MW at 36209.8 Da
NOV3a,	MDLSLCTFNLFIYPTKRENHTVIREFVFQGFSSFHEHKLTLFVVFLTLCLLTLAGNVI
CG109541-01
Protein Sequence	IVTIISIDRHLHTPMYFFVSMLSTSETVYTLVIVPRMLSSLLSLSQPISLGGCATQMF
	FITLAINNCFLLTAMGYDRYVAICNPLRYMIIMNKKVCVQLVCGSCSVGLLVAIVQIS
	SVFRLPFCDKQVAHYFCDIHPVMKLSCVDTTLHDLINFVVSSLVIVVPLGLVFISYIL
	IISTILKVTSPEGRKKAFATCASHLTVVIIHYGCASIAYLKPKSENTRDQDQLISVTY
	TVFTPLLNPVVYTLRNKEVKNALHRAIGKKPFA

[0330] Further analysis of the NOV3a protein yielded the following properties shown in Table 3B.

TABLE 3B
Protein Sequence Properties NOV3a
PSort     0.6000 probability located in plasma membrane; 0.4000
analysis: probability located in Golgi body; 0.3000 probability
          located in endoplasmic reticulum (membrane); 0.3000
          probability located in microbody (peroxisome)
SignalP   Cleavage site between residues 55 and 56
analysis:

[0331] A search of the NOV3a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 3C.

TABLE 3C
Geneseq Results for NOV3a
		NOV3a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAG71822	Human olfactory receptor	14 . . . 323	310/311 (99%)	e−176
	polypeptide, SEQ ID NO: 1503 -	1 . . . 311	310/311 (99%)
	Homo sapiens, 336 aa.
	[WO200127158-A2, 19 APR. 2001]
AAG72013	Human olfactory receptor	16 . . . 320	236/306 (77%)	e−138
	polypeptide, SEQ ID NO: 1694 -	2 . . . 307	276/306 (90%)
	Homo sapiens, 309 aa.
	[WO200127158-A2, 19 APR. 2001]
AAG73036	Olfactory receptor-like polypeptide,	16 . . . 319	218/305 (71%)	e−128
	SEQ ID NO: 2718 - Unidentified, 309	2 . . . 306	267/305 (87%)
	aa. [WO200127158-A2, 19 APR. 2001]
AAE18021	Human G-protein coupled receptor-8a	16 . . . 319	212/305 (69%)	e−124
	(GPCR-8a) protein - Homo sapiens,	2 . . . 306	260/305 (84%)
	309 aa. [WO200206342-A2, 24 JAN. 2002]
AAU85247	G-coupled olfactory receptor #108 -	16 . . . 319	209/305 (68%)	e−124
	Homo sapiens, 309 aa.	2 . . . 306	262/305 (85%)
	[WO200198526-A2, 27 DEC. 2001]

[0332] In a BLAST search of public sequence datbases, the NOV3a protein was found to have homology to the proteins shown in the BLASTP data in Table 3D.

TABLE 3D
Public BLASTP Results for NOV3a
		NOV3a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q8VFS1	Olfactory receptor MOR267-8 - Mus	17 . . . 323	262/308 (85%)	e−151
	musculus (Mouse), 310 aa.	3 . . . 310	285/308 (92%)
P30954	Olfactory receptor 10J1 (Olfactory	16 . . . 320	236/306 (77%)	e−138
	receptor-like protein HGMP07J) -	13 . . . 318	276/306 (90%)
	Homo sapiens (Human), 320 aa.
Q62007	Odorant receptor - Mus musculus	16 . . . 319	218/305 (71%)	e−127
	(Mouse), 309 aa.	2 . . . 306	267/305 (87%)
Q8VES0	Olfactory receptor MOR267-13 -	21 . . . 319	216/300 (72%)	e−126
	Mus musculus (Mouse), 304 aa	2 . . . 301	264/300 (88%)
	(fragment).
Q8VGE0	Olfactory receptor MOR267-3 - Mus	17 . . . 323	214/310 (69%)	e−124
	musculus (Mouse), 313 aa.	3 . . . 312	263/310 (84%)

[0333] PFam analysis predicts that the NOV3a protein contains the domains shown in the

TABLE 3E
Domain Analysis of NOV3a
		Identities/
	NOV3a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
7tm_1	55 . . . 302	46/275 (17%)	7.4e−39
		172/275 (63%)

Example 4

[0334] The NOV4 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4A.

TABLE 4A
NOV4 Sequence Analysis
	SEQ ID NO: 19	1106 bp
NOV4a,	GCGCGCCCGCTGCTCGGTGGCAGGAGGGCCGGCGGAGCGCCATGGCCTGCATCCTGAA
CG110223-01 DNA
Sequence	GAGAAAGTCTGTGATTGCTGTGAGCTTCATAGCAGCGTTCCTTTTCCTGCTGGTTGTG
	CGTCTTGTAAATGAAGTGAATTTCCCATTGCTACTAAACTGCTTTGGACAACCTGGTA
	CAAAGTGGATACCATTCTCCTACACATACAGGCGGCCCCTTCGAACTCACTATGGATA
	CATAAATGTGAAGACACAAGAGCCTTTGCAACTGGACTGTGACCTTTGTGCCATAGTG
	TCAAACTCAGGTCAGATGGTTGGCCAGAAGGTGGGAAATGAGATAGATCGATCCTCCT
	GCATTTGGAGAATGAACAATGCCCCCACCAAAGGTTATGAAGAAGATGTCGGCCGCAT
	GACCATGATTCGAGTTGTGTCCCATACCAGCGTTCCTCTTTTGCTAAAAAACCCTGAT
	TATTTTTTCAAGGAAGCGAATACTACTATTTATGTTATTTGGGGACCTTTCCGCAATA
	TGAGGAAAGATGGCAATGGCATCGTTTACAACATGTTGAAAAAGACAGTTGGTATCTA
	TCCGAATGCCCAAATATACGTGACCACAGAGAAGCGCATGAGTTACTGTGATGGAGTT
	TTTAAGAAGGAAACTGGGAAGGACAGTACAGAGCATGCAGTGTTGATTGATCAAGGGT
	GGTTTACATTCATTCTGGCCATGGACGCCTGTTATGGCATTCACGTCTACGGGATGAT
	AAATGACACCTACTGCAAGACAGAAGGGTATAGAAAAGTCCCCTACCATTATTATGAA
	CAAGGAAGAGATGAGTGTGATGAATATTTTCTTCATGAACATGCCCCATATGGGGGCC
	ATAGGTTTATCACTGAAAAGAAAGTGTTTGCTAAATGGGCCAAGAAGCACAGGATAAT
	ATTTACACATCCAAACTGGACATTGTCTTGATAATGGTTTTCCTGATCTTGCCGCATC
	ACTTAATGTGATCCCCATACTGCAACTGTGATGCTGATGATGCTAATGGAGATGATGG
	TAATGATAAAGACAACAACAATGATTATCAAGTTCCTGTACACTCTCAGATGTGGATG
	GTGA
	ORF Start: ATG at 42	ORF Stop: TGA at 957
	SEQ ID NO: 20	305 aa	MW at 35409.7 Da
NOV4a,	MACILKRKSVIAVSFIAAFLFLLVVRLVNEVNFPLLLNCFGQPGTKWIPFSYTYRRPL
CG110223-01
Protein Sequence	RTHYGYINVKTQEPLQLDCDLCAIVSNSGQMVGQKVGNEIDRSSCIWRMNNAPTKGYE
	EDVGRMTMIRVVSHTSVPLLLKNPDYFFKEANTTIYVIWGPFRNMRKDGNGIVYNMLK
	KTVGIYPNAQIYVTTEKRMSYCDGVFKKETGKDSTEHAVLIDQGWFTFILAMDACYGI
	HVYGMINDTYCKTEGYRKVPYHYYEQGRDECDEYFLHEHAPYGGHRFITEKKVFAKWA
	KKHRIIFTHPNWTLS
	SEQ ID NO: 21	966 bp
NOV4b,	AATTCGCCCTTAAGCGCCATGGCCTGCATCCTGAAGAGAAAGTCTGTGATTGCTGTGA
CG110223-02 DNA
Sequence	GCTTCATAGCAGCGTTCCTTTTCCTGCTGGTTGTGCGTCTTGTAAATGAAGTGAATTT
	CCCATTGCTACTAAACTGCTTTGGACAACCTGGTACAAAGTGGATACCATTCTCCTAC
	ACATACAGGCGGCCCCTTCGAACTCACTATGGATACATAAATGTGAAGACACAAGAGC
	CTTTGCAACTGGACTGTGACCTTTGTGCCATAGTGTCAAACTCAGGTCAGATGGTTGG
	CCAGAAGGTGGGAAATGAGATAGATCGATCCTCCTGCATTTGGAGAATGAACAATGCC
	CCCACCAAAGGTTATGAAGAAGATGTCGGCCGCATGACCATGATTCGAGTTGTGTCCC
	ATACCAGCGTTCCTCTTTTGCTAAAAAACCCTGATTATTTTTTCAAGGAAGCGAATAC
	TACTATTTATGTTATTTGGGGACCTTTCCGCAATATGAGGAAAGATGGCAATGGCATC
	GTTTACAACATGTTGAAAAAGACAGTTGGTATCTATCCGAATGCCCAAATATACGTGA
	CCACAGAGAAGCGCATGAGTTACTGTGATGGAGTTTTTAAGAAGGAAACTGGGAAGGA
	CAGAGTCCAGTCTGGCTCATATCTCAGCACAGGGTGGTTTACCTTCCTTCTGGCCATG
	GACGCCTGTTATGGCATTCACGTCTACGGGATGATAAATGACACCTACTGTAAGACAG
	AAGGGTATAGAAAAGTCCCCTACCATTATTATGAACAAGGAAGAGATGAGTGTGATGA
	ATATTTTCTTCATGAACATGCCCCATATGGGGGTCATAGGTTTATCACTGAAAAGAAA
	GTGTTTGCTAAATGGGCCAAGAAGCACAGGATAATATTTACACATCCAAACTGGACAT
	TGTCTTGATAATGGTTTTCCTGATCTTGCCGCATCACT
	ORF Start: ATG at 19	ORF Stop: TGA at 934
	SEQ ID NO: 22	305 aa	MW at 35394.7 Da
NOV4b,	MACILKRKSVIAVSFIAAFLFLLVVRLVNEVNFPLLLNCFGQPGTKWIPFSYTYRRPL
CG110223-02
Protein Sequence	RTHYGYINVKTQEPLQLDCDLCAIVSNSGQMVGQKVGNEIDRSSCIWRMNNAPTKGYE
	EDVGRMTMIRVVSHTSVPLLLKNPDYFFKEANTTIYVIWGPFRNMRKDGNGIVYNMLK
	KTVGIYPNAQIYVTTEKRMSYCDGVFKKETGKDRVQSGSYLSTGWFTFLLAMDACYGI
	HVYGMINDTYCKTEGYRKVPYHYYEQGRDECDEYFLHEHAPYGGHRFITEKKVFAKWA
	KKHRIIFTHPNWTLS
	SEQ ID NO: 23	1005 bp
NOV4c,	AATTCGCCCTTAAGCGCCATGGCCTGCATCCTGAAGAGAAAGTCTGTGATTGCTGTGA
CG110223-03 DNA
Sequence	GCTTCATAGCAGCGTTCCTTTTCCTGCTGGTTGTGCGTCTTGTAAATGAAGTGAATTT
	CCCATTGCTACTAAACTGCTTTGGACAACCTGGTACAAAGTGGATACCATTCTCCTAC
	ACATACAGGCGGCCCCTTCGAACTCACTATGGATACATAAATGTGAAGACACAAGAGC
	CTTTGCAACTGGACTGTGACCTTTGTGCCATAGTGTCAAACTCAGGTCAGATGGTTGG
	CCAGAAGGTGGGAAATGAGATAGATCGATCCTCCTGCATTTGGAGAATGAACAATGCC
	CCCACCAAAGGTTATGAAGAAGATGTCGGCCGCATGACCATGATTCGAGTTGTGTCCC
	ATACCAGCGTTCCTCTTTTGCTAAAAAACCCTGATTATTTTTTCAAGGAAGCGAATAC
	TACTATTTATGTTATTTGGGGACCTTTCCGCAATATGAGGAAAGATGGCAATGGCATC
	GTTTACAACATGTTGAAAAAGACAGTTGGTATCTATCCGAATGCCCAAATATACGTGA
	CCACAGAGAAGCGCATGAGTTACTGTGATGGAGTTTTTAAGAAGGAAACTGGGAAGGA
	CAGTGTATTATCTACACTGCAATCAAAATCTTCCTTCCAAATAGTCCAGTCTGGCTCA
	TATCTCAGCACAGGGTGGTTTACCTTCATTCTGGCCATGGACGCCTGTTATGGCATTC
	ACGTCTACGGGATGATAAATGACACCTACTGCAAGACAGAAGGGTATAGAAAAGTCCC
	CTACCATTATTATGAACAAGGAAGAGATGAGTGTGATGAATATTTTCTTCATGAACAT
	GCCCCATATGGGGGTCATAGGTTTATCACTGAAAAGAAAGTGTTTGCTAAATGGGCCA
	AGAAGCACAGGATAATATTTACACATCCAAACTGGACATTGTCTTGATAATGGTTTTC
	CTGATCTTGCCGCATCACT
	ORF Start: ATG at 19	ORF Stop: TGA at 973
	SEQ ID NO: 24	318 aa	MW at 36745.2 Da
NOV4c,	MACILKRKSVIAVSFIAAFLFLLVVRLVNEVNFPLLLNCFGQPGTKWIPFSYTYRRPL
CG110223-03
Protein Sequence	RTHYGYINVKTQEPLQLDCDLCAIVSNSGQMVGQKVGNEIDRSSCIWRMNNAPTKGYE
	EDVGRMTMIRVVSHTSVPLLLKNPDYFFKEANTTIYVIWGPFRNMRKDGNGIVYNMLK
	KTVGIYPNAQIYVTTEKRMSYCDGVFKKETGKDSVLSTLQSKSSFQIVQSGSYLSTGW
	FTFILAMDACYGIHVYGMINDTYCKTEGYRKVPYHYYEQGRDECDEYFLHEHAPYGGH
	RFITEKKVFAKWAKKHRIIFTHPNWTLS

[0335] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 4B.

TABLE 4B
Comparison of NOV4a against NOV4b and NOV4c.
	NOV4a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV4b	1 . . . 305	270/305 (88%)
	1 . . . 305	273/305 (88%)
NOV4c	1 . . . 305	272/318(85%)
	1 . . . 318	274/318 (85%)

[0336] Further analysis of the NOV4a protein yielded the following properties shown in Table 4C.

TABLE 4C
Protein Sequence Properties NOV4a
PSort     0.8200 probability located in outside: 0.5246 probability
analysis: located in lysosome (lumen); 0.1783 probability located in
          microbody (peroxisome); 0.1000 probability located in
          endoplasmic reticulum (membrane)
SignalP   Cleavage site between residues 31 and 32
analysis:

[0337] A search of the NOV4a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 4D.

TABLE 4D
Geneseq Results for NOV4a
		NOV4a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAE05186	Human drug metabolising enzyme	1 . . . 210	210/210 (100%)	e−123
	(DME-17) protein - Homo sapiens,	1 . . . 210	210/210 (100%)
	210 aa. [WO200151638-A2, 19 JUL. 2001]
AAU29291	Human PRO polypeptide sequence	1 . . . 210	210/210 (100%)	e−123
	#268 - Homo sapiens, 210 aa.	1 . . . 210	210/210 (100%)
	[WO200168848-A2, 20 SEP. 2001]
AAB42269	Human ORFX ORF2033 polypeptide	1 . . . 210	205/210 (97%)	e−120
	sequence SEQ ID NO: 4066 - Homo	1 . . . 210	208/210 (98%)
	sapiens, 210 aa. [WO200058473-A2,
	05 OCT. 2000]
AAB75350	Human secreted protein #9 - Homo	63 . . . 302	120/242 (49%)	1e−70
	sapiens, 302 aa. [WO200100806-A2,	58 . . . 299	168/242 (68%)
	04 JAN. 2001]
AAB61614	Human protein HP03380 - Homo	63 . . . 302	120/242 (49%)	1e−70
	sapiens, 302 aa. [WO200102563-A2,	58 . . . 299	168/242 (68%)
	11 JAN. 2001]

[0338] In a BLAST search of public sequence datbases, the NOV4a protein was found to have homology to the proteins shown in the BLASTP data in Table 4E.

TABLE 4E
Public BLASTP Results for NOV4a
		NOV4a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q64686	Alpha-N-acetylgalactosaminide alpha-	1 . . . 305	253/305 (82%)	e−158
	2,6-sialyltransferase III (EC 2.4.99.-)	1 . . . 305	277/305 (89%)
	(ST6GalNAc III) (Sialyltransferase 7C)
	(STY) - Rattus norvegicus (Rat), 305 aa.
Q9WUV2	Alpha-N-acetylgalactosaminide alpha-	1 . . . 305	251/305 (82%)	e−156
	2,6-sialyltransferase (EC 2.4.99.-)	1 . . . 305	275/305 (89%)
	(ST6GALNACIII) - Mus musculus
	(Mouse), 305 aa.
Q9W6U6	Alpha-N-acetylgalactosamine alpha-2,6-	73 . . . 304	127/233 (54%)	9e−75
	sialyltransferase - Fugu rubripes	2 . . . 234	165/233 (70%)
	(Japanese pufferfish) (Takifugu
	rubripes), 234 aa (fragment).
Q9R2B6	(alpha-N-acetyl-NEURAMLNYL-2,3-	63 . . . 302	123/242 (50%)	9e−71
	beta-galactosyl-1,3)-N-	116 . . . 357	166/242 (67%)
	acetylgalactosaminide alpha-2,6-
	sialyltransferase (EC 2.4.99.-) (Alpha-N-
	acetylgalactosaminide alpha-2,6-
	sialyltransferase) (ST6GALNACIV) -
	Mus musculus (Mouse), 360 aa.
Q9H4F1	Alpha2,6-sialyltransferase - Homo	63 . . . 302	121/242 (50%)	9e−71
	sapiens (Human), 302 aa.	58 . . . 299	168/242 (69%)

[0339] PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4F.

TABLE 4F
Domain Analysis of NOV4a
		Identities/
	NOV4a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
Glyco_transf_29	19 . . . 289	85/332 (26%)	7.4e−73
		227/332 (68%)

Example 5

[0340] The NOV5 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 5A.

TABLE 5A
NOV5 Sequence Analysis
	SEQ ID NO: 25	3123 bp
NOV5a,	GGCCTGGCACCTTCCCGGCCTGCCGCAGGGATGGGGCAGCTGTGCTGGCTGCCGCTGC
CG110311-01 DNA
Sequence	TGGCACCGCTCCTGTTGCTGCGACCGCCAGGGGTCCAGTCCGCCGGCCCCATCCGGGC
	CTTCGTGGTGCCCCACAGCCACATGGACGTGGGCTGGGTCTACACTGTGCAGGAAAGC
	ATGCGGGCGTACGCCGCCAATGTCTACACCTCAGTGGTGGAAGAGCTGGCCCGCGGCC
	AGCAGCGCCGGTTCATCGCTGTGGAGCAGGAGTTTTTCCGGCTGTGGTGGGATGGCGT
	CGCCTCGGACCAGCAGAAATACCAGGTACGCCAGCTCCTGGAGGAAGGACGCCTGGAA
	TTTGTCATCGGAGGCCAGGTCATGCATGACGAGGCTGTGACGCACCTTGATGACCAGA
	TCCTGCAGCTCACAGAAGGACACGGGTTTCTCTATGAAACATTTGGGATCCGGCCACA
	GTTCTCCTGGCACGTTGACCCGTTTGGCGCCTCTGCCACGACGCCCACCCTATTTGCG
	CTGGCGGGCTTCAATGCCCACCTCGGCTCCCGGATCGACTACGACCTGAAGGCAGCCA
	TGCAGGAGGCCCGGGTGCTGCAGTTCGTGTGGCGAGGGTCCCCATCCCTCTCAGAGCG
	GCAGGAAATCTTCACGCACATCATGGACCAGTACAGCTACTGCACCCCGTCCCACATC
	CCTTTCTCCAACAGGTCAGGATTTTACTGGAATGGCGTGGCTGTCTTCCCCAAGCCTC
	CCCAAGATGGGGTGTACCCCAACATGAGTGAGCCTGTCACCCCAGCCAACATCAACCT
	CTATGCCGAGGCCCTGGTGGCCAACGTGAAGCAGAGGGCCGCCTGGTTCCGGACACCG
	CACGTCCTCTGGCCCTGGGGATGTGACAAGCAGTTCTTCAATGCCTCGGTGCAGTTTG
	CCAACATGGACCCGCTGCTGGACCACATCAACAGCCATGCTGCCGAGCTCGGTGTCTC
	GGTGCAGTATGCCACGCTGGGCGACTACTTCCGTGCCCTGCACGCTCTCAATGTCACC
	TGGCGTGTCCGCGACCACCACGACTTCCTGCCCTATTCCACAGAACCATTCCAGGCCT
	GGACGGGCTTCTACACGTCCCGCAGCTCACTGAAGGGGCTGGCCCGGCGAGCCAGCGC
	CTTGTTGTATGCCGGGGAGTCCATGTTCACACGCTACCTGTGGCCGGCCCCCCGTGGG
	CATCTGGACCCCACCTGGGCCCTGCAGCAGCTCCAGCAGCTTCGCTGGGCCGTCTCCG
	AGGTACAGCACCATGATGCCATCACTGGGACTGAGTCCCCCAAGGTGAGAGACATGTA
	CGCAACGCACCTGGCCTCGGGGATGCTGGGCATGCGCAAGCTGATGGCCTCCATCGTC
	CTAGATGAGCTCCAGCCCCAGGCACCCATGGCGGCCAGCTCCGGTGAGCAGGGCCCTG
	CAGGGAGGCCTTCTCTGTGTGCAGATGCAGGACCTGCAGGACATTTTGCCTCGGTCTA
	CAACCCGCTGGCCTGGACGGTCACCACCATCGTCACCCTGACTGTTGGTTTCCCTGGA
	GTCCGCGTCACAGATGAGGCGGGCCACCCAGTGGCCTTGCAGATCCAGAACTCAACAG
	AGACCCCATCTGCGTATGACCTGCTTATTCTGACCACAATCCCAGGCCTCAGTTACCG
	GCACTACAACATCAGACCCACTGCAGGGGCCCAAGAGGGCACCCAGGAGCCGGCTGCC
	ACTGTGGCGAGCACCCTTCAATTTGGCCGCAGGCTGAGGAGACGCACCAGCCATGCGG
	GCAGGTACTTGGTGCCTGTGGCAAACGACTGCTACATTGTGCTGCTCGACCAGGATAC
	CAACCTGATGCACAGCATCTGGGAGAGACAGAGTAACCGAACGGTGCGCGTGACCCAG
	GAATTCCTGGAGTACCACGTCAACGGGGATGTGAAACAGGGCCCCATTTCCGATAACT
	ACCTGTTCACACCGGGCAAGGCCGCGGTGCCTGCGTGGGAAGCTGTGGAAATGGAGAT
	TGTGGCGGGACAGCTTGTGACTGAGATCCGGCAGTACTTCTACAGGAACATGACAGCA
	CAGAATTACACGTATGCAATCCGCTCCCGGCTCACCCATGTGCCGCAGGGCCATGACG
	GGGAGCTGCTCTGCCACCGGATAGAGCAGGAGTACCAAGCCGGCCCCCTGGAGCTGAA
	CCGTGAGGCTGTCCTGAGGACCAGCACCAACCTAAACAGCCAGCAGGTCATCTACTCA
	GACAACAACGGCTACCAGATGCAGCGGAGGCCCTACGTTTCCTATGTGAACAACAGCA
	TCGCCCGGAATTACTACCCCATGGTTCAGTCGGCCTTCATGGAGGATGGCAAAAGCAG
	GCTTGTGTTGCTGTCGGAGCGGGCACATGGCATCTCCAGCCAAGGGAATGGGCAGGTG
	GAGGTAATGCTCCACCGGCGGCTGTGGAACAACTTCGACTGGGACCTGGGCTACAACC
	TCACGCTGAACGACACCTCAGTCGTCCACCCAGTGCTCTGGCTTCTGCTGGGATCCTG
	GTCCCTCACCACTGCCCTGCGCCAGAGGAGCGCACTGGCGCTGCAGCACAGGCCCGTG
	GTGCTGTTCGGAGACCTCGCTGGTAAAGGGGCACCCCTCCCAGGACCCCAGCAGCAAG
	AGGCCGTGACGCTGCCCCCGAATCTTCACCTGCAGATCCTGAGCATCCCTGGCTGGCG
	CTACAGCTCCAACCACACGGAGCACTCTCAGAATCTCCGGAAAGGTCATCGAGGGGAA
	GCCCAGGCTGACCTCCGCCGTGTCCTGCTGCGGCTCTACCACCTATATGAAGTGGGCG
	AGGACCCAGTCCTGTCTCAGCCAGTGACAGTGAATCTGGAGGTGGTGCTGCAGGCGCT
	GGGGTCCGTGGTGGCAGTGGAGGAGCGCTCGCTCACAGGGACCTGGGATTTGAGCATG
	CTGCACCGCTGGAGCTGGAGGACGGGGCCTGGCCGCCACAGAGGTGACACCACCTCTC
	CCTCGAGGCCACCAGGAGGCCCCATCATCACCGTCCACCCAAAGGAAATCCGGACGTT
	CTTTATTCACTTTCAACAGCAGTGAGCCCTGGGCAGATGCCCCGGCCCC
	ORF Start: ATG at 31	ORF Stop: TGA at 3097
	SEQ ID NO: 26	1022 aa	MW at 115228.5 Da
NOV5a,	MGQLCWLPLLAPLLLLRPPGVQSAGPIRAFVVPHSHMDVGWVYTVQESMRAYAANVYT
CGJ10311-01
Protein Sequence	SVVEELARGQQRRFIAVEQEFFRLWWDGVASDQQKYQVRQLLEEGRLEFVIGGQVMHD
	EAVTHLDDQILQLTEGHGFLYETFGIRPQFSWHVDPFGASATTPTLFALAGFNAHLGS
	RIDYDLKAAMQEARVLQFVWRGSPSLSERQEIFTHIMDQYSYCTPSHIPFSNRSGFYW
	NGVAVFPKPPQDGVYPNMSEPVTPANINLYAEALVANVKQRAAWFRTPHVLWPWGCDK
	QFFNASVQFANMDPLLDHINSHAAELGVSVQYATLGDYFRALHALNVTWRVRDHHDFL
	PYSTEPFQAWTGFYTSRSSLKGLARRASALLYAGESMFTRYLWPAPRGHLDPTWALQQ
	LQQLRWAVSEVQHHDAITGTESPKVRDMYATHLASGMLGMRKLMASIVLDELQPQAPM
	AASSGEQGPAGRPSLCADAGPAGHFASVYNPLAWTVTTIVTLTVGFPGVRVTDEAGHP
	VALQIQNSTETPSAYDLLILTTIPGLSYRHYNIRPTAGAQEGTQEPAATVASTLQFGR
	RLRRRTSHAGRYLVPVANDCYIVLLDQDTNLMHSIWERQSNRTVRVTQEFLEYHVNGD
	VKQGPISDNYLFTPGKAAVPAWEAVEMEIVAGQLVTEIRQYFYRNMTAQNYTYAIRSR
	LTHVPQGHDGELLCHRIEQEYQAGPLELNREAVLRTSTNLNSQQVIYSDNNGYQMQRR
	PYVSYVNNSIARNYYPMVQSAFMEDGKSRLVLLSERAHGISSQGNGQVEVMLHRRLWN
	NFDWDLGYNLTLNDTSVVHPVLWLLLGSWSLTTALRQRSALALQHRPVVLFGDLAGKG
	APLPGPQQQEAVTLPPNLHLQILSIPGWRYSSNHTEHSQNLRKGHRGEAQADLRRVLL
	RLYHLYEVGEDPVLSQPVTVNLEVVLQALGSVVAVEERSLTGTWDLSMLHRWSWRTGP
	GRHRGDTTSPSRPPGGPIITVHPKEIRTFFIHFQQQ

[0341] Further analysis of the NOV5a protein yielded the following properties shown in Table 5B.

TABLE 5B
Protein Sequence Properties NOV5a
PSort     0.4132 probability located in outside; 0.2562 probability
analysis: located in microbody (peroxisome); 0.1900 probability located
          in lysosome (lumen); 0.1000 probability located in
          endoplasmic reticulum (membrane)
SignalP   Cleavage site between residues 24 and 25
analysis:

[0342] A search of the NOV5a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 5C.

TABLE 5C
Geneseq Results for NOV5a
		NOV5a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU84380	Novel human secreted or	1 . . . 1022	1001/1022 (97%)	0.0
	membrane−associated protein #19 -	1 . . . 1009	1001/1022 (97%)
	Homo sapiens, 1009 aa.
	[WO200204600-A2, 17 JAN. 2002]
AAB43158	Human ORFX ORF2922	132 . . . 952	797/821 (97%)	0.0
	polypeptide sequence SEQ ID	1 . . . 808	799/821 (97%)
	NO: 5844 - Homo sapiens, 823 aa.
	[WO200058473-A2, 05 OCT. 2000]
AAM93642	Human polypeptide, SEQ ID NO:	751 . . . 1022	267/272 (98%)	e−157
	3497 - Homo sapiens, 272 aa.	1 . . . 272	267/272 (98%)
	[EP1130094-A2, 05 SEP. 2001]
AAB86944	Human chromosome 19 derived	27 . . . 1020	294/1044 (28%)	1e−80
	protein (peptide sequence 4) - Homo	76 . . . 1019	451/1044 (43%)
	sapiens, 1245 aa. [DE10061931-A1,
	06 SEP. 2001]
ABG09539	Novel human diagnostic protein	27 . . . 968	278/979 (28%)	9e−78
	#9530 - Homo sapiens, 1168 aa.	76 . . . 958	431/979 (43%)
	[WO200175067-A2, 11 OCT. 2001]

[0343] In a BLAST search of public sequence datbases, the NOV5a protein was found to have homology to the proteins shown in the BLASTP data in Table 5D.

TABLE 5D
Public BLASTP Results for NOV5a
		NOV5a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9Y2E5	Epididymis-specific alpha-	1 . . . 1022	996/1022 (97%)	0.0
	mannosidase precursor (EC 3.2.1.24)	1 . . . 1009	999/1022 (97%)
	(Mannosidase alpha class 2B member
	2) - Homo sapiens (Human), 1009 aa.
O54782	Epididymis-specific alpha-	1 . . . 1021	769/1021 (75%)	0.0
	mannosidase precursor (EC 3.2.1.24)	1 . . . 1018	853/1021 (83%)
	(Mannosidase alpha class 2B member
	2) - Mus musculus (Mouse), 1018 aa.
T42762	probable alpha-mannosidase (EC	1 . . . 1022	682/1023 (66%)	0.0
	3.2.1.24) - pig, 1006 aa.	12 . . . 1006	778/1023 (75%)
Q28949	Epididymis-specific alpha-	1 . . . 1022	682/1023 (66%)	0.0
	mannosidase precursor (EC 3.2.1.24)	1 . . . 995	778/1023 (75%)
	(Mannosidase alpha class 2B member
	2) (AMAN) - Sus scrofa (Pig), 995
	aa.
A42265	alpha-mannosidase (EC 3.2.1.24) -	27 . . . 1009	294/1035 (28%)	8e−97
	slime mold (Dictyostelium	42 . . . 999	479/1035 (45%)
	discoideum), 1005 aa.

[0344] PFam analysis predicts that the NOV5a protein contains the domains shown in the Table 5E.

TABLE 5E
Domain Analysis of NOV5a
		Identitites/
	NOV5a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
Glyco_hydro_38	1 . . . 627	250/715 (35%)	3.7e−270
		550/715 (77%)

Example 6

[0345] The NOV6 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 6A.

TABLE 6A.
NOV6 Sequence Analysis
	SEQ ID NO: 27	726 bp
NOV6a,	TTCGCCCTACTCTGTCACCTCCGCTGGAAGGAGTGGAACCCAGACTTGCTGGTCTGAT
CG110421-01 DNA
Sequence	CCATGCAGATGGCCAGGCTGCTAGGCCTCTGTGCCTGGGCACGGAAGTCGGTGCGGAT
	GGCCAGCTCCAGGATGACCCGCCGGGACCCGCTCACAAATAAGGTGGCCCTGGTAACG
	GCCTCCACCGACGGGATCGGCTTCGCCATCGCCCGGCGTTTGGCCCAGGACAGGGCCC
	ACGTGGTCGTCAGCAGCCGGAAGCAGCAGAATGTGGACCAGGCGGTGGCCACGCTGCA
	GGGGGAGGGGCTGAGCGTGACGGGCACTGTGTGCCATGTGGGGAAGGCGGAGGACCGG
	GAGCGGCTGGTGGCCATGGCTGTGAAGCTTCATGGAGGTATCGATATCCTAGTCTCCA
	ATGCTGCTGTCAACCCTTTCTTTGGAAGCCTAATGGATGTCACCGAGGAGGTGTGGGA
	CAAGCTCTGGATGGACAAGGAAAAAGAGGAAAGCATGAAAGAAACCCTGCGGATAAGA
	AGGTTAGGCGAGCCAGAGGATTGTGCTGGCATCGTGTCTTTCCTGTGCTCTGAAGATG
	CCAGCTACATCACTGGGGAAACAGTGGTGGTGGGTGGAGGAACCCCGTCCCGCCTCTG
	AGGACCGGGAGACAGCCCACAGGCCAGAGTTGGGCTCTAGCTCCTGGTGCTGTTCCCG
	CATTCACCCACTGGCCTTTCCCACCTCTGC
	ORF Start: ATG at 61	ORF Stop: TGA at 637
	SEQ ID NO: 28	192 aa	MW at 20905.8 Da
NOV6a,	MQMARLLGLCAWARKSVRMASSRMTRRDPLTNKVALVTASTDGIGFAIARRLAQDRAH
CG110421-01
Protein Sequence	VVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVAMAVKLHGGIDILVSN
	AAVNPFFGSLMDVTEEVWDKLWMDKEKEESMKETLRIRRLGEPEDCAGIVSFLCSEDA
	SYITGETVVVGGGTPSRL
	SEQ ID NO: 29	984 bp
NOV6b,	TTCGCCCTACTCTGTCACCTCCGCTGGAAGGAGTGGAACCCAGACTTGCTGGTCTGAT
CG110421-02 DNA
Sequence	CCATGCAGATGGCCAGGCTGCTAGGCCTCTGTGCCTGGGCACGGAAGTCGGTGCGGAT
	GGCCAGCTCCAGGATGACCCGCCGGGACCCGCTCACAAATAAGGTGGCCCTGGTAACG
	GCCTCCACCGACGGGATCGGCTTCGCCATCGCCCGGCGTTTGGCCCAGGACAGGGCCC
	ACGTGGTCGTCAGCAGCCGGAAGCAGCAGAATGTGGACCAGGCGGTGGCCACGCTGCA
	GGGGGAGGGGCTGAGCGTGACGGGCACTGTGTGCCATGTGGGGAAGGCGGAGGACCGG
	GAGCGGCTGGTGGCCATGGCTGTGAAGCTTCATGGAGGTATCGATATCCTAGTCTCCA
	ATGCTGCTGTCAACCCTTTCTTTGGAAGCCTAATGGATGTCACCGAGGAGGTGTGGGA
	CAAGACTCTGGACATTAATGTGAAGGCCCCAGCCCTGATGACAAAGGCAGTGGTGCCA
	GAAATGGAGAAACGAGGGGGCGGCTCAGTGGTGATCGTGTCTTCCATAGCAGCCTTCA
	GTCCATCTCCTGGCTTCAGTCCTTACAATGTCAGTAAAACAGCCTTGCTGGGCCTGAC
	CAAGACCCTGGCCATAGAGCTGGCCCCAAGGAACATTAGGGTGAACTGCCTAGCACCT
	GGACTTATCAAGACTAGCTTCAGCAGGATGCTCTGGATGGACAAGGAAAAAGAGGAAA
	GCATGAAAGAAACCCTGCGGATAAGAAGGTTAGGCGAGCCAGAGGATTGTGCTGGCAT
	CGTGTCTTTCCTGTGCTCTGAAGATGCCAGCTACATCACTGGGGAAACAGTGGTGGTG
	GGTGGAGGAACCCCGTCCCGCCTCTGAGGACCGGGAGACAGCCCACAGGCCAGAGTTG
	GGCTCTAGCTCCTGGTGCTGTTCCCGCATTCACCCACTGGCCTTTCCCACCTCTGC
	ORF Start: ATG at 61	ORF Stop: TGA at 895
	SEQ ID NO: 30	278 aa	MW at 29902.4 Da
NOV6b,	MQMARLLGLCAWARKSVRMASSRMTRRDPLTNKVALVTASTDGIGFAIARRLAQDRAH
CG110421-02
Protein Sequence	VVVSSRKQQNVDQAVATLQGEGLSVTGTVCHVGKAEDRERLVAMAVKLHGGIDILVSN
	AAVNPFFGSLMDVTEEVWDKTLDINVKAPALMTKAVVPEMEKRGGGSVVIVSSIAAFS
	PSPGFSPYNVSKTALLGLTKTLAIELAPRNIRVNCLAPGLIKTSFSRMLWMDKEKEES
	MKETLRIRRLGEPEDCAGIVSFLCSEDASYITGETVVVGGGTPSRL

[0346] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 6B.

TABLE 6B
Comparison of NOV6a against NOV6b.
	NOV6a Residues/	Identitites/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV6b	1 . . . 136	136/136 (100%)
	1 . . . 136	136/136 (100%)

[0347] Further analysis of the NOV6a protein yielded the following properties shown in Table 6C.

TABLE 6C
Protein Sequence Properties NOV6a
PSort     0.8538 probability located in mitochondrial matrix space;
analysis: 0.8000 probability located in microbody (peroxisome); 0.5377
          probability located in mitochondrial inner membrane; 0.5377
          probability located in mitochondrial intermembrane space
SignalP   Cleavage site between residues 19 and 20
analysis:

[0348] A search of the NOV6a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 6D.

TABLE 6D
Geneseq Results for NOV6a
		NOV6a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU18501	Human endocrine polypeptide SEQ	1 . . . 192	181/192 (94%)	5e−97
	ID No 456 - Homo sapiens, 193 aa.	2 . . . 193	181/192 (94%)
	[WO200155364-A2, 02 AUG. 2001]
AAU23017	Novel human enzyme polypeptide	1 . . . 192	181/192 (94%)	5e−97
	#103 - Homo sapiens, 193 aa.	2 . . . 193	181/192 (94%)
	[WO200155301-A2, 02 AUG. 2001]
ABB10365	Human cDNA SEQ ID NO: 673 -	1 . . . 192	181/192 (94%)	5e−97
	Homo sapiens, 193 aa.	2 . . . 193	181/192 (94%)
	[WO200154474-A2, 02 AUG. 2001]
AAB58822	Breast and ovarian cancer associated	15 . . . 192	148/183 (80%)	1e−73
	antigen protein sequence SEQ ID	7 . . . 183	152/183 (82%)
	530 - Homo sapiens, 183 aa.
	[WO200055173-A1, 21 SEP. 2000]
AAY68735	Short chain alcohol dehydrogenase−	1 . . . 136	133/136 (97%)	5e−70
	related molecule ScRM-1 protein -	1 . . . 136	134/136 (97%)
	Homo sapiens, 278 aa.
	[WO200004135-A2, 27 JAN. 2000]

[0349] In a BLAST search of public sequence datbases, the NOV6a protein was found to have homology to the proteins shown in the BLASTP data in Table 6E.

TABLE 6E
Public BLASTP Results for NOV6a
		NOV6a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q8TD03	NADP-dependent retinol	19 . . . 192	169/174 (97%)	3e−91
	dehydrogenase short isoform - Homo	1 . . . 174	170/174 (97%)
	sapiens (Human), 174 aa.
Q9BTZ2	Peroxisomal short-chain alcohol	1 . . . 136	125/136 (91%)	9e−63
	dehydrogenase - Homo sapiens	1 . . . 136	126/136 (91%)
	(Human), 278 aa.
Q9NV08	CDNA FIJ11008 fis. clone	1 . . . 136	124/136 (91%	3e−62
	PLACE1003100, moderately similar	1 . . . 136	125/136 (91%)
	to HEP27 protein - Homo sapiens
	(Human), 278 aa.
O95162	Peroxisomal short-chain alcohol	19 . . . 136	115/118 (97%)	5e−58
	dehydrogenase - Homo sapiens	1 . . . 118	115/118 (97%)
	(Human), 260 aa.
Q9H3N5	NADPH-dependent retinol	19 . . . 136	113/118 (95%)	4e−57
	dehydrogenase/reductase - Homo	1 . . . 118	114/118 (95%)
	sapiens (Human), 260 aa.

[0350] PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6F.

TABLE 6F
Domain Analysis of NOV6a
		Identitites/
	NOV6a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
sodcu	69 . . . 87	10/20 (50%)	0.4
		16/20 (80%)
adh_short	31 . . . 188	65/271 (24%)	1.8e−06
		124/271 (46%)

Example 7

[0351] The NOV7 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 7A.

TABLE 7A.
NOV7 Sequence Analysis
	SEQ ID NO: 31	1106 bp
NOV7a,	CCCGCTTGCCTCAGCTGCAGCAGCGGGAAGCTCGGTGGCAAGCCCTTGTAGTCCTGTG
CG110531-01 DNA
Sequence	CGATGGCGTCTCGATATGACAGGGCGATCACTGTCTTCTCCCCAGACGGACACCTTTT
	TCAAGTTGAATATGCCCAGGAAGCGGTGAAGAAAGGATCCACCGCGGTCGGAATTCGA
	GGTACCAATATAGTTGTTCTTGGGGTAGAAAAAAAATCTGTTGCCAAGCTTCAAGATG
	AAAGAACTGTGAGGAAAATTTGTGCCCTTGATGACCATGTCTGCATGGCTTTTGCAGG
	ACTTACTGCTGATGCTAGAGTAGTAATAAACAGAGCCCGTGTGGAGTGCCAGAGCCAT
	AAGCTTACGGTTGAGGACCCAGTCACTGTAGAATACATAACTCGCTTCATAGCAACTT
	TAAAGCAGAAATATACCCAAAGCAATGGACGAAGACCTTTTGGTATTTCTGCCTTAAT
	TGTAGGTTTTGATGATGATGGTATCTCAAGATTGTATCAGACAGATCCTTCTGGTACT
	TATCATGCTTGGAAGGCAAATGCAATAGGCCGAAGTGCTAAAACTGTTCGAGAATTTC
	TAGAAAAGAATTACACAGAAGATGCCATAGCAAGTGACAGTGAAGCTATCAAGTTAGC
	AATAAAAGCTTTGCTAGAAGTTGTCCAGTCTGGTGGAAAAAACATTGAACTTGCTATA
	ATAAGAAGAAATCAACCTTTGAAGATGTTTAGTGCAAAAGAAGTTGAATTATATGTAA
	CTGAAATAGAAAAGGAAAAGGAAGAAGCAGAGAAGAAAAAATCAAAGAAATCTGTCTA
	ATTCTTAGGATGACCACTGGGAGGTCTTAATGTTTTGTTTTATTGTACTGCCTGAGGT
	TGTTTAGTGAAATTTTAGAGGAAAACAGTTATTTTGCAGCATTACATGCAGTACTTGT
	GTGATGTTTTGAGAATGCCAGATCTGTGGCTGTCTTCATTCTATTACATAGTCAAACA
	TAGGTTTATGTGAAGATTTTCTTTGAAAGGGGATTTCAGTAATTGTTGAGAGCAGTCA
	TAATTCCACATAAGCCTGAGACTCTATAATTTGTCCAGTGTCTTACTTACCTTCATAT
	ATGC
	ORF Start: ATG at 61	ORF Stop: TAA at 811
	SEQ ID NO: 32	250 aa	MW at 27842.6 Da
NOV7a,	MASRYDRAITVFSPDGHLFQVEYAQEAVKKGSTAVGIRGTNIVVLGVEKKSVAKLQDE
CG110531-01
Protein Sequence	RTVRKICALDDHVCMAFAGLTADARVVINRARVECQSHKLTVEDPVTVEYITRFIATL
	KQKYTQSNGRRPFGISALIVGFDDDGISRLYQTDPSGTYHAWKANAIGRSAKTVREFL
	EKNYTEDAIASDSEAIKLAIKALLEVVQSGGKNIELAIIRRNQPLKMFSAKEVELYVT
	EIEKEKEEAEKKKSKKSV
	SEQ ID NO: 33	1106 bp
NOV7b,	CCCGCTTGCCTCAGCTGCAGCAGCGGGAAGCTCGGTGGCAAGCCCTTGTAGTCCTGTG
CG110531-02 DNA
Sequence	CGATGGCGTCTCGATATGACAGGGCGATCACTGTCTTCTCCCCAGACGGACACCTTTT
	TCAAGTTGAATATGCCCAGGAAGCGGTGAAGAAAGGATCCACCGCGGTCGGAATTCGA
	GGTACCAATATAGTTGTTCTTGGGGTAGAAAAAAAATCTGTTGCCAAGCTTCAAGATG
	AAAGAACTGTGAGGAAAATTTGTGCCCTTGATGACCATGTCTGCATGGCTTTTGCAGG
	ACTTACTGCTGATGCTAGAGTAGTAATAAACAGAGCCCGTGTGGAGTGCCAGAGCCAT
	AAGCTTACGGTTGAGGACCCAGTCACTGTAGAATACATAACTCGCTTCATAGCAACTT
	TAAAGCAGAAATATACCCAAAGCAATGGACGAAGACCTTTTGGTATTTCTGCCTTAAT
	TGTAGGTTTTGATGATGATGGTATCTCAAGATTGTATCAGACAGATCCTTCTGGTACT
	TATCATGCTTGGAAGGCAAATGCAATAGGCCGAAGTGCTAAAACTGTTCGAGAATTTC
	TAGAAAAGAATTACACAGAAGATGCCATAGCAAGTGACAGTGAAGCTATCAAGTTAGC
	AATAAAAGCTTTGCTAGAAGTTGTCCAGTCTGGTGGAAAAAACATTGAACTTGCTATA
	ATAAGAAGAAATCAACCTTTGAAGATGTTTAGTGCAAAAGAAGTTGAATTATATGTAA
	CTGAAATAGAAAAGGAAAAGGAAGAAGCAGAGAAGAAAAAATCAAAGAAATCTGTCTA
	ATTCTTAGGATGACCACTGGGAGGTCTTAATGTTTTGTTTTATTGTACTGCCTGAGGT
	TGTTTAGTGAAATTTTAGAGGAAAACAGTTATTTTGCAGCATTACATGCAGTACTTGT
	GTGATGTTTTGAGAATGCCAGATCTGTGGCTGTCTTCATTCTATTACATAGTCAAACA
	TAGGTTTATGTGAAGATTTTCTTTGAAAGGGGATTTCAGTAATTGTTGAGAGCAGTCA
	TAATTCCACATAAGCCTGAGACTCTATAATTTGTCCAGTGTCTTACTTACCTTCATAT
	ATGC
	ORF Start: ATG at 61	ORF Stop: TAA at 811
	SEQ ID NO: 34	250 aa	MW at 27842.6 Da
NOV7b,	MASRYDRAITVFSPDGHLFQVEYAQEAVKKGSTAVGIRGTNIVVLGVEKKSVAKLQDE
CG110531-02
Protein Sequence	RTVRKICALDDHVCMAFAGLTADARVVINRARVECQSHKLTVEDPVTVEYITRFIATL
	KQKYTQSNGRRPFGISALIVGFDDDGISRLYQTDPSGTYHAWKANAIGRSAKTVREFL
	EKNYTEDAIASDSEAIKLAIKALLEVVQSGGKNIELAIIRRNQPLKMFSAKEVELYVT
	EIEKEKEEAEKKKSKKSV

[0352] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 7B.

TABLE 7B
Comparison of NOV7a against NOV7b.
	NOV7a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV7b	1 . . . 232	232/232 (100%)
	1 . . . 232	232/232 (100%)

[0353] Further analysis of the NOV7a protein yielded the following properties shown in Table 7C.

TABLE 7C
Protein Sequence Properties NOV7a
PSort     0.4500 probability located in cytoplasm; 0.3000 probability
analysis: located in microbody (peroxisome); 0.1000 probability located
          in mitochondrial matrix space; 0.1000 probability located in
          lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0354] A search of the NOV7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 7D.

TABLE 7D
Geneseq Results for NOV7a
		NOV7a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU23135	Novel human enzyme polypeptide	1 . . . 250	250/250 (100%)	e−138
	#221 - Homo sapiens, 253 aa.	4 . . . 253	250/250 (100%)
	[WO200155301-A2, 02 AUG. 2001]
AAB35090	Proteasome subunit XAPC7 protein	5 . . . 249	208/245 (84%)	e−117
	sequence - Unidentified, 248 aa.	3 . . . 247	228/245 (92%)
	[WO200072008-A2, 30 NOV. 2000]
AAW73284	Human proteasome subunit protein	5 . . . 249	208/245 (84%)	e−117
	PSUBB - Homo sapiens, 248 aa.	3 . . . 247	228/245 (92%)
	[U.S. Pat. No. 5843715-A, 01 DEC. 1998]
AAR94597	XAPC7 protein - Homo sapiens, 248 aa.	5 . . . 249	208/245 (84%)	e−117
	[WO9611207-A1, 18 APR. 1996]	3 . . . 247	228/245 (92%)
ABB59877	Drosophila melanogaster	1 . . . 248	177/249 (71%)	1e−97
	polypeptide SEQ ID NO 6423 -	1 . . . 249	209/249 (83%)
	Drosophila melanogaster, 249 aa.
	[WO200171042-A2, 27 SEP. 2001]

[0355] In a BLAST search of public sequence datbases, the NOV7a protein was found to have homology to the proteins shown in the BLASTP data in Table 7E.

TABLE 7E
Public BLASTP Results for NOV7a
		NOV7a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9CWH6	2410072D24Rik protein - Mus	1 . . . 249	237/249 (95%)	e−131
	musculus (Mouse), 250 aa.	1 . . . 249	245/249 (98%)
Q8TAA3	Similar to proteasome subunit alpha	1 . . . 236	235/242 (97%)	e−128
	type 7 (Proteasome subunit RC6-1) -	1 . . . 242	236/242 (97%)
	Homo sapiens (Human), 242 aa.
Q9PTW9	Proteasome subunit alpha type 7 (EC	1 . . . 249	223/250 (89%)	e−123
	3.4.25.1) (Proteasome subunit alpha 4) -	1 . . . 250	239/250 (95%)
	Carassius auratus (Goldfish), 251 aa.
Q9Z2U0	Proteasome subunit alpha type 7 (EC	5 . . . 249	210/245 (85%)	e−118
	3.4.25.1) (Proteasome subunit RC6-1)	3 . . . 247	229/245 (92%)
	Mus musculus (Mouse), 248 aa.
O14818	Proteasome subunit alpha type 7 (EC	5 . . . 249	208/245 (84%)	e−116
	3.4.25.1) (Proteasome subunit RC6-1)	3 . . . 247	228/245 (92%)
	(Proteasome subunit XAPC7) - Homo
	sapiens (Human), 248 aa.

[0356] PFam analysis predicts that the NOV7a protein contains the domains shown in the Table 7F.

TABLE 7F
Domain Analysis of NOV7a
		Identities/
	NOV7a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
proteasome	33 . . . 179	63/153 (41%)	3.5e−52
		119/153 (78%)

Example 8

[0357] The NOV8 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 8A.

TABLE 8A.
NOV8 Sequence Analysis
	SEQ ID NO: 35	1143 bp
NOV8a,	ATGCTTAGCACAGTGTACAGTCTAGCGGACCCGGACCTGCGGCCGCTGCTCCCGGTCC
CG111231-01 DNA
Sequence	GCAGCCTCACAGGGGAGCGGCTTCCGGTGCTGCCTGCGTCATCTCCGCGCGTCCCTCA
	GCTCCGCGGCTCCCGGCGGAAGCGGCGGAAGCGGCTGCACTTCCGGTCCCCGCCCGGAGATGTGAAA
	GTTCTTGAAATTAAGAATAAGGCAAGAAAATTGAACATCGAACCCCTAAGAAGTAATC
	TCTCCAAATATTATGTCCTGAGCCAGTCAGAAATATGTAAAGGGAAGAACATTTTTTT
	GCTGTCTCTTATCTTCAGTAGCCCAGGAAATGGAACAAGACGGGACCTCATTAGGAAA
	ACTTGGGGCAATGTGACCAGTGTCCAAGGGCATCCCATTCTCACACTGTTTGCTCTGG
	GAATGCCTGTTTCGGTAACTACCCAGAAAGAGATCAACAAAGAATCCTGTAAGAATAA
	TGATATAATTGAAGGAATCTTCTTGGACAGTTCTGAGAACCAAACCCTGAAGATCATT
	GCAATGATACAGTGGGCTGTGGCTTTCTGCCCTAATGCCCTGTTCATTCTCAAGGTGG
	ATGAAGAGACGTTTGTCAATCTACCAAGCTTGGTAGACTATCTTCTCAATCTGAAAGA
	ACACCTAGAAGATATCTATGTAGGAAGAGTTCTTCATCAGGTTACACCCAATAGAGAT
	CCTCAGAACAGAGACTTTGTCCCTCTTAGTGAGTACCCAGAAAAATACTACCCAGATT
	ACTGCAGTGGTGAGGCCTTTATAATGTCCCAAGATGTGGCTCGAATGATGTATGTGGT
	TTTCAAAGAAGTACCCATGATGGTGCCAGCTGATGTGTTTGTAGGAATTTGTGCTAAG
	TTCATTGGCCTTATACCCATCCACAGCTCAAGGTTTTCTGGGAAAAGGCACATTAGAT
	ACAACAGATGTTGCTATAAGTTCATTTTTACATCCTCAGAAATTGCAGATCCTGAAAT
	GCCCCTAGCATGGAAGGAAATTAATGATGGAAAAGAATGTACACTGTTTGAGACATCC
	TATGAGCTCATTTCCTGCAAACTTCTGACGTACCTTGACAGCTTTAAACGTTTTCACA
	TGGGGACCATAAAAAACAATCTCATGTATTTTGCTGATTAG
	ORF Start: ATG at 1	ORF Stop: TAG at 1141
	SEQ ID NO: 36	380 aa	MW at 43495.1 Da
NOV8a,	MLSTVYSLADPDLRPLLPVRSLTGERLPVLPASSPRVPQLRGSRRKRLHFRSPPGDVK
CG111231-01
Protein Sequence	VLEIKNKARKLNIEPLRSNLSKYYVLSQSEICKGKNIFLLSLIFSSPGNGTRRDLIRK
	TWGNVTSVQGHPILTLFALGMPVSVTTQKEINKESCKNNDIIEGIFLDSSENQTLKII
	AMIQWAVAFCPNALFILKVDEETFVNLPSLVDYLLNLKEHLEDIYVGRVLHQVTPNRD
	PQNRDFVPLSEYPEKYYPDYCSGEAFIMSQDVARMMYVVFKEVPMMVPADVFVGICAK
	FIGLIPIHSSRFSGKRHIRYNRCCYKFIFTSSEIADPEMPLAWKEINDGKECTLFETS
	YELISCKLLTYLDSFKRFHMGTIKNNLMYFADt

[0358] Further analysis of the NOV8a protein yielded the following properties shown in Table 8B.

TABLE 8B
Protein Sequence Properties NOV8a
PSort     0.8500 probability located in endoplasmic reticulum
analysis: (membrane); 0.4400 probability located in plasma membrane;
          0.1000 probability located in mitochondrial inner membrane;
          0.1000 probability located in Golgi body
SignalP   No Known Signal Sequence Predicted
analysis:

[0359] A search of the NOV8a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 8C.

TABLE 8C
Geneseq Results for NOV8a
		NOV8a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB07522	Human drug metabolizing enzyme	82 . . . 357	96/284 (33%)	2e−41
	(DME) (ID: 3419318CD1) - Homo	75 . . . 357	161/284 (55%)
	sapiens, 378 aa. [WO200204612-A2,
	17 JAN. 2002]
AAE04752	Human beta-1,3-galactosyltransferase	82 . . . 357	96/284 (33%)	2e−41
	homologue, ZNSSP8 - Homo	75 . . . 357	161/284 (55%)
	sapiens, 378 aa. [WO200144479-A1,
	21 JUN. 2001]
AAW95171	Protein exhibiting betal,3-	96 . . . 362	92/301 (30%)	3e−37
	galactosyltransferase activity -	72 . . . 371	152/301 (49%)
	Unidentified, 371 aa. [JP11056373-A,
	02 MAR. 1999]
AAM93908	Human polypeptide, SEQ ID NO:	83 . . . 362	96/322 (29%)	8e−37
	4057 - Homo sapiens, 378 aa.	57 . . . 378	157/322 (47%)
	[EP1130094-A2, 05 SEP. 2001]
AAY34171	Human galactosyltransferase,	83 . . . 362	96/322 (29%)	8e−37
	HUGA-1, protein sequence - Homo	57 . . . 378	157/322 (47%)
	sapiens, 378 aa. [U.S. Pat. No. 5955282-A,
	21 SEP. 1999]

[0360] In a BLAST search of public sequence datbases, the NOV8a protein was found to have homology to the proteins shown in the BLASTP data in Table 8D.

TABLE 8D
Public BLASTP Results for NOV8a
		NOV8a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9BYG0	Beta1,3-N-	82 . . . 357	96/284 (33%)	5e−41
	acetylglucosaminyltransferase 5 (Beta	75 . . . 357	161/284 (55%)
	1,3 N-acetyglucosaminyltransferase Lc3
	synthase) (Gal-betal-3 GlcNAc-
	transferase) - Homo sapiens (Human),
	378 aa.
O88178	Beta-1,3-galactosyltransferase 4 (EC	96 . . . 362	92/301 (30%)	8e−37
	2.4.1.62) (Ganglioside	72 . . . 371	152/301 (49%)
	galactosyltransferase) (UDP-
	galactose:beta-N-acetyl-galactosamine−
	beta-1,3-galactosyltransferase) (GAL-
	T2) - Rattus norvegicus (Rat), 371 aa.
Q9Z0F0	Beta-1,3-galactosyltransferase 4 (EC	83 . . . 362	96/316 (30%)	1e−36
	2.4.1.62) (Ganglioside	57 . . . 371	159/316 (49%)
	galactosyltransferase) (UDP-
	galactose:beta-N-acetyl-galactosamine-
	beta-1,3-galactosyltransferase) (GAL-
	T2) - Mus musculus (Mouse), 371 aa.
Q91VC1	GM1/GD1b/GA1 synthase - Mus	83 . . . 337	92/285 (32%)	2e−36
	musculus (Mouse), 370 aa (fragment).	57 . . . 340	147/285 (51%)
Q920U7	GM1/GD1b/GA1 synthase - Mus	83 . . . 337	92/285 (32%)	2e−36
	spicilegus (Steppe mouse), 370 aa	57 . . . 340	147/285 (51%)
	(fragment).

[0361] PFam analysis predicts that the NOV8a protein contains the domains shown in the Table 8E.

TABLE 8E
Domain Analysis of NOV8a
		Identities/
	NOV8a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
Galactosyl_T	109 . . . 300	62/210 (30%)	2.6e−55
		140/210 (67%)

Example 9

[0362] The NOV9 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 9A.

TABLE 9A.
NOV9 Sequence Analysis
	SEQ ID NO: 37	1182 bp
NOV9a,	GAATTCGGGGGGAGAACAGAGTGGACGGAGAGTAGGAGAGACCGAAAAGGCTGGGGGT
CG111293-02 DNA
Sequence	GGGAGTAGCGGATTTGAAGCACTTGTTGGCCTACAGAGGTGTGGCAAGCAGAGCACCT
	CAGAACTCAGGCGTACTGCCCGCCGCCCGAGCCCTGCGAGGGCCGATAGCGAGGGTGT
	GGCCCTTATCTGCACCCAGCAGAGCGCCGGCGGGGTACGGTCTTAGGACCTCGATCTC
	CTTCTCCCTCATTTTCTCTCATCCCTACCTATTGTGGGTTTCCGCATGGGCCGGACCG
	TGGTCGTGCTGGGCGGAGGCATCAGCGGCTTGGCCGCCAGTTACCACCTGAGCCGGGC
	CCCCTGCCCCCCTAAGGTGGTCCTAGTGGAGAGCAGTGAGCGTCTGGGAGGCTGGATT
	CGCTCCGTTCGAGGCCCTAATGGTGCTATCTTTGAGCTTGGACCTCGGGGAATTAGGC
	CAGCGGGAGCCCTAGGGGCCCGGACCTTGCTCCTGGTATCTCTAAGGGACAGCAGTCT
	GGAGGCTGACCACGTTATTAGTGCCATTCCAGCTTCAGTGCTCAGTGAGCTGCTCCCT
	GCTGAGGCTGCCCCTCTGGCTCGTGCCCTGAGTGCCATCACTGCAGTGTCTGTAGCTG
	TGGTGAATCTGCAGTACCAAGGAGCCCATCTGCCTGTCCAGGGATTTGGACATTTGGT
	GCCATCTTCAGAAGATCCAGGAGTCCTGGGAATCGTGTATGACTCAGTTGCTTTCCCT
	GAGCAGGACGGGAGCCCCCCTGGCCTCAGAGTGACTGTGATGCTGGGAGGTTCCTGGT
	TACAGACACTGGAGGCTAGTGGCTGTGTCTTATCTCAGGAGCTGTTTCAACAGCGGGC
	CCAGGAAGCAGCTGCTACACAATTAGGACTGAAGGAGATGCCGAGCCACTGCTTGGTC
	CATCTACACAAGAACTGCATTCCCCAGTATACACTAGGTCACTGGCAAAAACTAGAGT
	CAGCTAGGCAATTCCTGACTGCTCACAGGTTGCCCCTGACTCTGGCTGGAGCCTCCTA
	TGAGGGAGTTGCTGTTAATGACTGTATAGAGAGTGGGCGCCAGGCAGCAGTCAGTGTC
	CTGGGCACAGAACCTAACAGCTGATCCCCAACTCTCATTCATGAAAATAAAAATTGCT
	GGAGCTCCCGAATCCCGAATTC
	ORF Start: ATG at 278	ORF Stop: TGA at 1124
	SEQ ID NO: 38	282 aa	MW at 29492.5 Da
NOV9a,	MGRTVVVLGGGISGLAASYHLSRAPCPPKVVLVESSERLGGWIRSVRGPNGAIFELGP
CG111293-02
Protein Sequence	RGIRPAGALGARTLLLVSLRDSSLEADHVISAIPASVLSELLPAEAAPLARALSAITA
	VSVAVVNLQYQGAHLPVQGFGHLVPSSEDPGVLGIVYDSVAFPEQDGSPPGLRVTVML
	GGSWLQTLEASGCVLSQELFQQRAQEAAATQLGLKEMPSHCLVHLHKNCIPQYTLGHW
	QKLESARQFLTAHRLPLTLAGASYEGVAVNDCIESGRQAAVSVLGTEPNS
	SEQ ID NO: 39	891 bp
NOV9b,	GAATTCGGGGGGAGAACAGAGTGGACGGAGAGTAGGAGAGACCGAAAAGGCTGGGGGT
CG111293-03 DNA
Sequence	GGGAGTAGCGGATTTGAAGCACTTGTTGGCCTACAGAGGTGTGGCAAGCAGAGCACCT
	CAGAACTCAGGCGTACTGCCCGCCGCCCGAGCCCTGCGAGGGCCGATAGCGAGGGTGT
	GGCCCTTATCTGCACCCAGCAGAGCGCCGGCGGGGTACGGTCTTAGGACCTCGATCTC
	CTTCTCCCTCATTTTCTCTCATCCCTACCTATTGTGGGTTTCCGCATGGGCCGGACCG
	TGGTTGTGCTGGGCGGAGGCGTCAGCGGCTTGGCCGCCAGTTACCACCTGAGCCGGGC
	CCCCTGCCCCCCTAAGGTGGTCCTAGTGGAGAGCAGTGAGCGTCTGGGAGGCTGGATT
	CGCTCCGTTCGAGGCCCTAATGGTGCTATCTTTGAGCTTGGACCTCGGGGAATTAGGC
	CAGCGGGAGCCCTAGGGGCCCGGACCTTGCTCCTGGTGATGCTGGGAGGTTCCTGGTT
	ACAGACACTAGAGGCTAGTGGCTGTGTCTTATCTCAGGAGCTGTTTCAACAGCGGGCC
	CAGGAAGCAGCTGCTACACAATTAGGACTGAAGGAGATGCCGAGCCACTGCTTGGTCC
	ATCTACACAAGAACTGCATTCCCCAGTATACACTAGGTCACTGGCAAAAACTAGAGTC
	AGCTAGGCAATTCCTGACTGCTCACAGGTTGCCCCTGACTCTGGCTGGAGCCTCCTAT
	GAGGGAGTTGCTGTTAATGACTGTATAGAGAGTGGGCGCCAGGCAGCAGTCAGTGTCC
	TGGGCACAGAACCTAACAGCTGATCCCCAACTCTCATTCATGAAAATAAAAATTGCTG
	GAGCTCCCGAATCCCGAATTC
	ORF Start: ATG at 278	ORF Stop: TGA at 833
	SEQ ID NO: 40	185 aa	MW at 19586.4 Da
NOV9b,	MGRTVVVLGGGVSGLAASYHLSRAPCPPKVVLVESSERLGGWIRSVRGPNGAIFELGP
CG111293-03
Protein Sequence	RGIRPAGALGARTLLLVMLGGSWLQTLEASGCVLSQELFQQRAQEAAATQLGLKEMPS
	HCLVHLHKNCIPQYTLGHWQKLESARQFLTAHRLPLTLAGASYEGVAVNDCIESGRQA
	AVSVLGTEPNS
	SEQ ID NO: 41	617 bp
0NOV9c,	CAGAGCGCCGGCGGGGTTTCCGCATGGGCCGGACCGTGGTCGTGCTGGGCGGAGGCAT
CG111293-04 DNA
Sequence	CGGCGGCTTGGCCGCCAGTTACCACCTGAGCCGGGCCCCCTGCCCCCCTAAGGTGGTC
	CTAGTGGAGAGCAGTGAGCGTCTGGGAGGCTGGATTCGCTCCGTTCGAGGCCCTAATG
	GTGCTATCTTTGAGCTTGGACCTCGGGGAATTAGGCCAGCGGGAGCCCTAGGGGCCCG
	GACCTTGCTCCTGGTGATGCTGGGAGGTTCCTGGTTACAGACACTGGAGGCTAGTGGC
	TGTGTCTTATCTCAGGAGCTGTTTCAACAGCGGGCCCAGGAAGCAGCTGCTACACAAT
	TAGGACTGAAGGAGATGCCGAGCCACTGCTTGGTCCATCTACACAAGAACTGCATTCC
	CCAGTATACACTAGGTCACTGGCAAAAACTAGAGTCAGCTAGGCAATTCCTGACTGCT
	CACAGGTTGCCCCTGACTCTGGCTGGAGCCTCCTATGAGGGAGTTGCTGTTAATGACT
	GTATAGAGAGTGGGCGCCAGGCAGCAGTCAGTGTCCTGGGCACAGAACCTAACAGCTG
	ATCCCCAACTCTCATTCATGAAAATAAAAATTGCTGG
	ORF Start: ATG at 24	ORF Stop: TGA at 579
	SEQ ID NO: 42	185 aa	MW at 19570.4 Da
NOV9c,	MGRTVVVLGGGIGGLAASYHLSRAPCPPKVVLVESSERLGGWIRSVRGPNGAIFELGP
CG111293-04
Protein Sequence	RGIRPAGALGARTLLLVMLGGSWLQTLEASGCVLSQELFQQRAQEAAATQLGLKEMPS
	HCLVHLHKNCIPQYTLGHWQKLESARQFLTAHRLPLTLAGASYEGVAVNDCIESGRQA
	AVSVLGTEPNS
	SEQ ID NO: 43	1638 bp
NOV9d,	GAATTCGGGGGGAGAACAGAGTGGACGGAGAGTAGGAGAGACCGAAAAGGCTGGGGGT
CG111293-05 DNA
Sequence	GGGAGTAGCGGATTTGAAGCACTTGTTGGCCTACAGAGGTGTGGCAAGCAGAGCACCT
	CAGAACTCAGGCGTACTGCCCGCCGCCCGAGCCCTGCGAGGGCCGATAGCGAGGGTGT
	GGCCCTTATCTGCACCCAGCAGAGCGCCGGCGGGGTACGGTCTTAGGACCTCGATCTC
	CTTCTCCCTCATTTTCTCTCATCCCTACCTATTGTGGGTTTCCGCATGGGCCGGACCG
	TGGTCGTGCTGGGCGGAGGCATCAGCGGCTTGGCCGCCAGTTACCACCTGAGCCGGGC
	CCCCTGCCCCCCTAAGGTGGTCCTAGTGGAGAGCAGTGAGCGTCTGGGAGGCTGGATT
	CGCTCCGTTCGAGGCCCTAATGGTGCTATCTTTGAGCTTGGACCTCGGGGAATTAGGC
	CAGCGGGAGCCCTAGGGGCCCGGACCTTGCTCCTGGTTTCTGAGCTTGGCTTGGATTC
	AGAAGTGCTGCCTGTCCGGGGAGACCACCCAGCTGCCCAGAACAGGTTCCTCTACGTG
	GGCGGTGCCCTGCATGCCCTACCCACTGGCCTCAGGGGGCTACTCCGCCCTTCACCCC
	CCTTCTCCAAACCTCTGTTTTGGGCTGGGCTGAGGGAGCTGACCAAGCCCCGGGGCAA
	AGAGCCTGATGAGACTGTGCACAGTTTTGCCCAGCGCCGCCTTGGACCTGAGGTGGCG
	TCTCTAGCCATGGACAGTCTCTGCCGTGGAGTGTTTGCAGGCAACAGCCGTGAGCTCA
	GCATCAGGTCCTGCTTTCCCAGTCTCTTCCAAGCTGAGCAAACCCATCGTTCCATATT
	ACTGGGCCTGTTGCTGGGGGCAGGGCGGACCCCACAGCCAGACTCAGCACTCATTCGC
	CAGGCCTTGGCTGAGCGCTGGAGCCAGTGGTCACTTCGTGGAGGTCTAGAGATGTTGC
	CTCAGGCCCTTGAAACCCACCTGACTAGTAGGGGGGTCAGTGTTCTCAGAGGCCAGCC
	GGTCTGTGGGCTCAGCCTCCAGGCAGAAGGGCGCTGGAAGGTATCTCTAAGGGACAGC
	AGTCTGGAGGCTGACCACGTTATTAGTGCCATTCCAGCTTCAGTGCTCAGTGAGCTGC
	TCCCTGCTGAGGCTGCCCCTCTGGCTCGTGCCCTGAGTGCCATCACTGCAGTGTCTGT
	AGCTGTGGTGAATCTGCAGTACCAAGGAGCCCATCTGCCTGTCCAGGTGATGCTGGGA
	GGTTCCTGGTTACAGACACTGGAGGCTAGTGGCTGTGTCTTATCTCAGGAGCTGTTTC
	AACAGCGGACCCAGGAAGCAGCTGCTACACAATTAGGACTGAAGGAGATGCCGAGCCA
	CTGCTTGGTCCATCTACACAAGAACTGCATTCCCCAGTATACACTAGGTCACTGGCAA
	AAACTAGAGTCAGCTAGGCAATTCCTGACTGCTCACAGGTTGCCCCTGACTCTGGCTG
	GAGCCTCCTATGAGGGAGTTGCTGTTAATGACTGTATAGAGAGTGGGCGCCAGGCAGC
	AGTCAGTGTCCTGGGCACAGAACCTAACAGCTGATCCCCAACTCTTCATTTCATGAAA
	ATAAAAATTGCTGG
	ORF Start: ATG at 278	ORF Stop: TGA at 1598
	SEQ ID NO: 44	440 aa	MW at 47015.6 Da
NOV9d,	MGRTVVVLGGGISGLAASYHLSRAPCPPKVVLVESSERLGGWIRSVRGPNGAIFELGP
CG111293-05
Protein Sequence	RGIRPAGALGARTLLLVSELGLDSEVLPVRGDHPAAQNRFLYVGGALHALPTGLRGLL
	RPSPPFSKPLFWAGLRELTKPRGKEPDETVHSFAQRRLGPEVASLAMDSLCRGVFAGN
	SRELSIRSCFPSLFQAEQTHRSILLGLLLGAGRTPQPDSALORQALAERWSQWSLRGG
	LEMLPQALETHLTSRGVSVLRGQPVCGLSLQAEGRWKVSLRDSSLEADHVISAIPASV
	LSELLPAEAAPLARALSAITAVSVAVVNLQYQGAHLPVQVMLGGSWLQTLEASGCVLS
	QELFQQRTQEAAATQLGLKEMPSHCLVHLHKNCIPQYTLGHWQKLESARQFLTAGRLF
	LTLAGASYEGVAVNDCIESGRQAAVSVLGTEPNS
	SEQ ID NO: 45	1089 bp
NOV9e,	GAATTCGGGGGGAGAACAGAGTGGACGGAGAGTAGGAGAGACCGAAAAGGCTGGGGGT
CG111293-06 DNA
Sequence	GGGAGTAGCGGATTTGAAGCACTTGTTGGCCTACAGAGGTGTGGCAAGCAGAGCACCT
	CAGAACTCAGGCGTACTGCCCGCCGCCCGAGCCCTGCGAGGGCCGATAGCGAGGGTGT
	GGCCCTTATCTGCACCCAGCAGAGCGCCGGCGGGGTACGGTCTTAGGACCTCGATCTC
	CTTCTCCCTCATTTTCTCTCATCCCTACCTATTGTGGGTTTCCGCATGGGCCGGACCG
	TGGTCGTGCTGGGCGGAGGCATCAGCGGCTTGGCCGCCAGTTACCACCTGAGCCGGGC
	CCCCTGCCCCCCTAAGGTGGTCCTAGTGGAGAGCAGTGAGCGTCTGGGAGGCTGGATT
	CGCTCCGTTCGAGGCCCTAATGGTGCTATCTTTGAGCTTGGACCTCGGGGAATTAGGC
	CAGCGGGAGCCCTAGGGGCCCGGACCTTGCTCCTGGTTTCTGAGCTTGGCTTGGATTC
	AGAAGTGCTGCCTGTCCGGGGAGACCACCCAGCTGCCCAGAACAGGTTCCTCTACGTG
	GGCGGTGCCCTGCATGCCCTACCCACTGGCCTCAGGGGGCTACTCCGCCCTTCACCCC
	CCTTCTCCAAACCTCTGTTTTGGGCTGGGCTGAGGGAGCTGACCAAGCCCCGGGGCAA
	AGAGCCTGATGAGACTGTGCACAGTTTTGCCCAGCGCCGCCTTGGACCTGAGGTGGCG
	TCTCTAGCCATGGACAGTCTCTGCCGTGGAGTGTTTGCAGGCAACAGCCGTGAGCTCA
	GCATCAGGTCCTGCTTTCCCAGTCTCTTCCAAGCTGAGCAAACCCATCGTTCCATATT
	ACTGGGCCTGCTGCTGGGGGCAGGGCGGACCCCACAGCCAGACTCAGCACTCATTCGC
	CAGGCCTTGGCTGGAGCCTCCTATGAGGGAGTTGCTGTTAATGACTGTATAGAGAGTG
	GGCGCCAGGCAGCAGTCAGTGTCCTGGGCACAGAACCTAACAGCTGATCCCCAACTCT
	CATTCATGAAAATAAAAATTGCTGGAGCTCCCGAATCCCGAATTC
	ORF Start: ATG at 278	ORF Stop: TGA at 1031
	SEQ ID NO: 46	251 aa	MW at 26438.0 Da
NOV9e,	MGRTVVVLGGGISGLAASYHLSRAPCPPKVVLVESSERLGGWIRSVRGPNGAIFELGP
CG111293-06
Protein Sequence	RGIRPAGALGARTLLLVSELGLDSEVLPVRGDHPAAQNRFLYVGGALHALPTGLRGLL
	RPSPPFSKPLFWAGLRELTKPRGKEPDETVHSFAQRRLGPEVASLAMDSLCRGVFAGN
	SRELSIRSCFPSLFQAEQTHRSILLGLLLGAGRTPQPDSALIRQALAGASYEGVAVND
	CIESGRQAAVSVLGTEPNS

[0363] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 9B.

TABLE 9B
Comparison of NOV9a against NOV9b through NOV9e.
Protein	NOV9a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV9b	172 . . . 282	111/111 (100%)
	75 . . . 185	111/111 (100%)
NOV9c	172 . . . 282	111/111 (100%)
	75 . . . 185	111/111 (100%)
NOV9d	23 . . . 282	165/273 (60%)
	207 . . . 440	173/273 (62%)
NOV9e	1 . . . 282	142/299 (47%)
	1 . . . 251	154/299 (51%)

[0364] Further analysis of the NOV9a protein yielded the following properties shown in Table 9C.

TABLE 9C
Protein Sequence Properties NOV9a
PSort     0.4944 probability located in outside; 0.1000 probability
analysis: located in endoplasmic reticulum (membrane); 0.1000
          probability located in endoplasmic reticulum (lumen); 0.1000
          probability located in microbody (peroxisome)
SignalP   Cleavage site between residues 18 and 19
analysis:

[0365] A search of the NOV9a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 9D.

TABLE 9D
Geneseq Results for NOV9a
		NOV9a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAY49537	Rat protoporphyrinogen oxidase -	75 . . . 282	179/208 (86%)	1e−97
	Rattus norvegicus, 477 aa.	270 . . . 477	190/208 (91%)
	[EP955380-A2, 10 NOV. 1999]
ABB61812	Drosophila melanogaster polypeptide	75 . . . 275	68/201 (33%)	3e−28
	SEQ ID NO 12228 - Drosophila	278 . . . 472	114/201 (55%)
	melanogaster, 475 aa.
	[WO200171042-A2, 27 SEP. 2001]
AAG78538	Yeast protox-3 amino acid sequence	118 . . . 272	60/160 (37%)	1e−15
	from pWDC-5 - Saccharomyces sp,	325 . . . 479	85/160 (52%)
	490 aa. [U.S. Pat. No. 6307129-B1, 23 OCT. 2001]
AAE13205	Arabidopsis thaliana	118 . . . 272	60/160 (37%)	1e−15
	protoporphyrinogen oxidase−3	325 . . . 479	85/160 (52%)
	(protox-3) - Arabidopsis thaliana, 490 aa.
	[U.S. Pat. No. 6288306-B1, 11 SEP. 2001]
AAW51257	Arabidopsis proto-porphyrinogen	118 . . . 272	60/160 (37%)	1e−15
	oxidase−3 (protox-3) - Arabidopsis	325 . . . 479	85/160 (52%)
	thaliana, 490 aa. [U.S. Pat. No. 5767373-A, 16 JUN. 1998]

[0366] In a BLAST search of public sequence datbases, the NOV9a protein was found to have homology to the proteins shown in the BLASTP data in Table 9E.

TABLE 9E
Public BLASTP Results for NOV9a
		NOV9a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P50336	Protoporphyrinogen oxidase (EC	23 . . . 282	224/273 (82%)	e−115
	1.3.3.4) (PPO) - Homo sapiens	207 . . . 477	232/273 (84%)
	(Human), 477 aa.
Q99M34	Protoporphyrinogen oxidase - Mus	75 . . . 282	181/208 (87%)	1e−97
	musculus (Mouse), 477 aa.	270 . . . 477	191/208 (91%)
P51175	Protoporphyrinogen oxidase (EC	75 . . . 282	181/208 (87%)	1e−97
	1.3.3.4) (PPO) - Mus musculus	270 . . . 477	191/208 (91%)
	(Mouse), 477 aa.
S65684	protoporphyrinogen oxidase -	75 . . . 282	180/208 (86%)	4e−96
	mouse, 477 aa.	270 . . . 477	190/208 (90%)
Q96SE3	Protoporphyrinogen oxidase -	135 . . . 282	148/148 (100%)	2e−82
	Homo sapiens (Human), 148 aa	1 . . . 148	148/148 (100%)
	(fragment).

[0367] PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9F.

TABLE 9F
Domain Analysis of NOV9a
		Identities/
	NOV9a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value

Example 10

[0368] The NOV10 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 10A.

TABLE 10A
NOV10 Sequence Analysis
	SEQ ID NO: 47	6915 bp
NOV10a,	ATGGATCTGTCAGACCTTGGAGAAGCCGCAGCCTTCCTCAGAAGAAGTGAAGCTGAGC
CG111455-01 DNA
Sequence	TGCTTCTACTACAGGCCACAGCCTTGGATGGGAAGAAGAAATGCTGGATTCCTGATGG
	TGAGAATGCTTATATCGAGGCTGAGGTAAAAGGGAGTGAAGATGATGGAACAGTAATT
	GTTGAGACAGCAGATGGACAGAGTCTGAGCATAAAGGAGGACAAAATCCAGCAGATGA
	ATCCTCCAGAGTTTGAAATGATTGAAGACATGGCAATGCTGACTCACCTCAATGAGGC
	ATCCGTGCTGCATACCCTGAAGCGGCGCTATGGCCAGTGGATGATCTATACATATTCA
	GGTCTCTTCTGTGTGACCATAAACCCTTACAAATGGCTTCCCGTGTATCAGAAAGAAG
	TCATGGCCGCCTACAAAGGGAAGAGGCGATCAGAGGCTCCCCCTCACATCTTTGCTGT
	TGCCAATAACGCCTTTCAGGACATGCTTCACAGTGGAGAATCTGGTGCTGGAAAGACT
	GTGAACAGCAAACATATTATCCAGTATTTTGCCACCATAGCAGCCATGATTGAATCCA
	GGAAAAAGGGGGCGTTAGAAGATCAAATCATGCAAGCGAATACTATCTTGGAAGCATT
	TGGAAATGCTAAAACCCTGAGAAATGACAACTCCTCTCGTTTTGGCAAATTCATCAGG
	ATGCACTTTGGTGCCAGAGGCATGCTGTCATCTGTGGACATTGATATCTTGCTTGAAA
	AGTCCAGGGTGATTTTCCAGCAGGCTGGAGAGAGGAACTACCACATATTCTATCAAAT
	TCTATCTGGACAAAAACCCACTCTAGACCTGCTCCTGGTATCTGCAAATCCCTCAGAC
	TTCCACTTTTGCTCCTGTGGAGCAGTTACTGTGGAGAGCTTGGATGATGCTGAAGAAT
	TGCTGGCCACAGAACAAGCCATGGACATCTTGGGCTTTCTTCCTGATGAGAAGTATGG
	ATGCTATAAACTCACTGGAGCCATCATGCACTTTGGAAATATGAAATTTAAACAGAAA
	CCTAGAGAAGAGCAACTGGAAGCAGATGGCACAGAAAGTGCTGACAAAGCTGCTTTCC
	TCATGGGCATTAACTCCTCTGAGTTGGTAAAGTGCTTGATCCATCCTAGAATCAAAGT
	TGGTAACGAATATGTTACCAGAGGTCAAACTATAGAACAGGTAACCTGTGCTGTCGGT
	GCCCTGTCCAAGTCAATGTATGAAAGGATGTTTAAGTGGCTAGTGGCACGGATCAACA
	GGGCCCTGGATGCCAAGCTGTCAAGGCAGTTCTTCATTGGCATTCTTGACATCACTGG
	TTTTGAAATCCTTGAGTATAATAGCCTTGAGCAACTTTGCATTAATTTTACCAATGAA
	AAATTACAACAATTCTTCAATTGGCACATGTTTGTTCTGGAGCAAGAGGAATATAAGA
	AAGAAAGCATTGAATGGGTGTCTATTGGCTTTGGTCTGGATTTGCAAGCTTGCATAGA
	TCTCATTGAGAAGCCAATGGGCATCCTTTCCATCCTTGAAGAAGAGTGTATGTTTCCT
	AAGGCTACAGACCTGACTTTCAAGACCAAACTCTTTGACAACCATTTTGGAAAGTCGG
	TTCATCTCCAGAAGCCCAAGCCTGATAAGAAGAAATTTGAAGCTCATTTTGAACTTGT
	CCATTATGCAGGAGTGGTACCTTATAATATCAGTGGTTGGCTGGAAAAGAACAAAGAC
	CTCCTTAATGAAACAGTGGTAGCTGTATTTCAGAAGTCTTCCAACAGACTCCTGGCGA
	GCCTTTTTGAAAATTACATGAGTACTGACAGTGGTGAGGGGGAGAAGAAACGAAAGAA
	AGGAGCTTCATTCCAAACGGTTGCATCTCTGCATAAAGAAAACCTGAATAAATTGATG
	ACTAATCTGAAATCAACAGCACCTCATTTTGTGAGATGCATAAATCCCAATGTGAACA
	AAATACCAGGTAAGCTGGACCCTTACTTGGTTCTACAGCAGTTGCGCTGTAATGGTGT
	CTTGGAAGGGACTAGGATATGCCGTGAAGGTTTTCCAAACCGACTGCAGTATGCTGAT
	TTTAAACAAAGGTACTGCATTCTGAATCCAAGGACCTTTCCAAAGAGCAAGTTTGTGA
	GCAGCAGAAAAGCAGCTGAAGAATTACTTGGCTCCTTGGAGATAGACCATACCCAGTA
	CCGATTTGGAATCACTAAGGTGTTTTTTAAAGCTGGGTTTCTGGGCCAACTGGAAGCA
	ATAAGAGATGAGAGACTATCTAAAGTCTTCACATTGTTCCAAGCCAGAGCACAGGGCA
	AACTGATGCGAATCAAATTCCAGAAGATTCTGGAAGAAAGGGATGCACTTATTTTGAT
	CCAATGGAACATAAGAGCTTTCATGGCTGTGAAGAACTGGCCCTGGATGAGGCTCTTC
	TTCAAGATCAAGCCTCTTGTTAAATCTTCAGAAGTAGGAGAAGAAGTAGCTGGACTGA
	AGGAAGAGTGTGCACAATTACAGAAAGCCTTGGAGAAATCAGAGTTTCAGAGGGAGGA
	ACTGAAAGCAAAGCAAGTATCCCTCACTCAGGAAAAAAATGACCTGATTCTTCAGCTT
	CAGGCTGAGCAAGAGACACTGGCAAATGTTGAAGAGCAGTGCGAGTGGCTGATTAAAT
	CCAAGATCCAGCTGGAGGCCAGAGTAAAGGAGCTGTCGGAGAGGGTGGAGGAAGAAGA
	GGAGATAAATTCTGAGCTGACTGCCAGGGGGCGGAAACTCGAAGATGAATGTTTTGAG
	TTGAAGAAAGAAATCGATGACCTGGAAACAATGTTGGTGAAGTCAGAGAAGGAGAAGC
	GTACTACAGAGCACAAGGTAAAGAACTTGACTGAGGAAGTAGAGTTTCTAAATGAGGA
	TATCAGCAAACTTAACAGAGCAGCCAAGGTTGTGCAGGAGGCCCATCAGCAGACCCTG
	GATGACCTGCACATGGAGGAGGAGAAGCTCAGCAGCCTGAGCAAAGCAAATCTGAAGC
	TGGAACAGCAAGTTGATCTTGAGGGTGCCCTTGAGCAGGAGAGAAAAGCGAGAATGAA
	CTGTGAAAGGGAACTGCACAAACTGGAGGGCAATTTAAAGCTGAATCGGGAAAGTATG
	GAGAACCTGGAAAGCAGCCAGCGACACCTGGCAGAAGAGCTGAGGAAAAAAGAATTAG
	AATTGAGTCAGATGAATTCAAAAGTGGAGAATGAGAAAGGCCTGGTAGCTCAGCTTCA
	GAAGACGGTTAAAGAGCTTCAGACTCAAATAAAGGATTTGAAAGAGAAACTAGAAGCT
	GAAAGGACCACTCGAGCCAAGATGGAAAGGGAGAGAGCTGACCTCACCCAAGACCTGG
	CTGACTTGAATGAGAGGCTGGAGGAGGTAGGAGGATCCAGTTTGGCTCAGCTGGAAAT
	AACTAAGAAACAGGAAACCAAATTCCAGAAGCTGCACCGAGACATGGAAGAGGCCACT
	CTGCACTTTGAGACAACTTCTGCATCTTTGAAGAAGAGACATGCAGACAGCCTGGCTG
	AGCTCGAGGGCCAGGTAGAAAATCTACAGCAGGTCAAGCAGAAACTGGAAAAAGACAA
	GAGTGACTTGCAGCTAGAAGTAGATGACCTCCTGACCCGTGTTGAGCAGATGACAAGA
	GCTAAGGCAAATGCTGAGAAACTCTGTACTCTATATGAAGAGCGCTTGCATGAAGCAA
	CTGCAAAGCTAGATAAGGTGACTCAGTTGGCAAATGACCTGGCAGCACAAAAGACAAA
	GCTGTGGAGTGAGAGTGGCGAGTTCCTACGGAGGCTTGAAGAGAAGGAGGCTCTGATA
	AACCAACTTTCCAGGGAAAAGAGCAACTTCACTCGGCAGATTGAAGACCTGAGAGGGC
	AGCTGGAAAAGGAGACCAAATCCCAGAGTGCCCTGGCCCATGCCCTGCAGAAGGCTCA
	GCGTGACTGTGACCTTCTACGAGAGCAGTATGAGGAAGAACAAGAGGTCAAGGCTGAG
	CTGCACCGGACCTTATCCAAAGTCAATGCTGAAATGGTGCAATGGAGAATGAAGTATG
	AAAACAATGTCATCCAGAGAACAGAAGACTTGGAGGATGCCAAGAAGGAACTGGCAAT
	TAGATTGCAGGAGGCAGCCGAAGCCATGGGGGTGGCCAATGCCAGAAATGCCTCCTTG
	GAGAGAGCCAGGCACCAGCTGCAGCTGGAGCTCGGGGACGCCCTGTCTGACCTCGGGA
	AGGTCCGCTCTGCAGCAGCCAGGCTGGACCAGAAGCAGCTGCAGTCTGGCAAGGCCCT
	TGCCGACTGGAAGCAGAAGCACGAGGAGTCCCAGGCGTTGCTGGATGCCTCTCAGAAG
	GAAGTTCAGGCTCTCAGTACAGAGCTCCTCAAGCTCAAGAACACCTATGAGGAGAGCA
	TCGTGGGCCAGGAGACACTCAGGAGGGAGAACAAGAACCTCCAAGAAGAGATTTCTAA
	TCTGACAAACCAGGTTAGAGAAGGGACCAAGAACTTAACTGAAATGGAAAAGGTCAAG
	AAACTAATTGAAGAAGAGAAGACAGAAGTCCAGGTGACACTGGAAGAAACAGAGGGAG
	CCCTGGAACGTAATGAAAGCAAGATTCTTCATTTCCAGCTTGAACTCTTGGAAGCTAA
	AGCAGAACTTGAAAGAAAGCTTTCAGAGAAAGATGAAGAAATAGAAAATTTTAGGAGG
	AAGCAGCAGTGTACCATTGACTCCCTGCAGTCTAGTCTGGATTCTGAAGCTAAGAGCA
	GAATTGAGGTTACCCGGCTGAAGAAGAAGATGGAAGAGGACCTCAATGAGATGGAACT
	CCAGCTTAGCTGTGCCAACCGGCAGGTGTCAGAAGCAACCAAATCCCTGGGCCAGCTT
	CAGATTCAAATCAAGGACCTTCAAATGCAGCTGGATGACAGCACACAACTGAACAGTG
	ATCTGAAGGAGCAGGTGGCTGTGGCTGAGCGGCGCAACTCTCTTCTTCAGTCTGAACT
	AGAGGATCTAAGGTCCCTGCAAGAGCAGACAGAGCGTGGCCGCAGGCTGTCAGAAGAA
	GAGCTCCTGGAAGCAACAGAAAGAATCAATCTTTTCTATACCCAGAACACAAGCCTCC
	TCAGCCAGAAGAAGAAACTGGAGGCTGATGTTGCCCGGATGCAGAAAGAAGCTGAAGA
	GGTGGTGCAGGAGTGTCAAAATGCAGAAGAGAAGGCCAAGAAGGCAGCCATTGAGGCA
	GCAAACTTGTCAGAAGAACTGAAGAAGAAGCAAGACACCATTGCCCACTTGGAAAGGA
	CAAGAGAAAATATGGAGCAGACAATTACAGACTTACAGAAAAGGCTGGCTGAAGCTGA
	ACAGATGGCCCTGATGGGGAGTAGAAAGCAAATCCAGAAACTAGAATCCAGGGTTCGT
	GAACTGGAAGGTGAACTGGAGGGTGAAATCCGTCGCAGTGCAGAGGCCCAGAGGGGAG
	CCCGCAGACTTGAGCGATGCATCAAAGAGCTGACCTATCAGGCAGAGGAAGACAAGAA
	GAATCTGAGCAGGATGCAAACTCAGATGGATAAACTTCAGCTAAAAGTGCAAAATTAC
	AAGCAGCAAGTCGAGGTGGCGGAAACACAAGCCAATCAATACCTTTCCAAGTATAAGA
	AACAGCAACATGAGTTGAATGAAGTGAAGGAAAGGGCAGAGGTGGCAGAATCTCAAGT
	CAATAAACTCAAAATTAAAGCAAGAGAGTTTGGGAAAAAGGTTCAAGAAGAATAGCAT
	CCCCTGCTTTGAAAGGACAACAGCTGGAGAAGTACAAGGAAGGTGCTGTTTCATGGCC
	AAAAACTTAGGTTGCATGGAAACATTTTTAAAAACATGTTTAAATTGCTTTTCACACC
	ATATAAACAAGGCAATTAGAAAAATAATTAAAGGGAATATCATTGCTTCCACAGTTAA
	TGGGGATTTTTTGATCCTCAAATGCAAGTAAACTACCTTCTAATGCTTCACATGACAG
	ATTAAATAAATGGAAGAACCTTTTCAATTCTGATGTTTAAAAAATGAATAAATACTTG
	ATCCTTTGTCCATATTTCCTCTTAATGGGTAGGACTCATAGAAGATGTCCTTAGACCA
	GTCACGCTTCATGGGGACTAGGGCATGTTGGTGAATGGTTTTTACTAAAGTTAGGCAA
	CTTTGGCTTGATTCACCCCTAAATCTATGAATGTATATTGTGAGCCAGCAGTGGTAGA
	ATGGAAGTCATAAGATCTCCTCAGCATTGTGATATAAATATAGCTATAGTTAGGCAAT
	TTGAACATGTAGGCAAAACTCTCCTAATCAACACACATGTAGGCTATATGCTGGTACA
	TGCTTTAAACATGGAGGTAACCCCACACGAGACATTCAGTGACAGGTAATATGCTGGA
	TTTGTGCAGTACCGATTTGGCTCAGCTGGAGGAACATGTCCCGGAATTCCTCTCTCTC
	ATGGTTCTGGATTGGAGTAGGTCATAAAGAAATTTGCATTAATTTGATCAGCAGCTAT
	TTTATACTCATAAGGTCAGTGTACAGACCCAAGCATGGTGACAGCTTGAAAATATGAC
	TCCAGGCCAAAAAGGGGAGCTAGAAGAGACCAGAGACAGCTCCCTGGACCCAGAGCTC
	TTCCAGCTCCTGCCAGCCTCCTCCTTCAGCTTTGCAAAGTACTGGCCAGGTGTGTGTG
	CAGCTCCATGGCAACCAGCATCAGCTTTTCCTGAGATCACACACAGCATTGCAGTGGA
	GGCCGTGAGACAGACATGGGTTCTGTTTGTTCTTATGGACTTCCCTTCATCCTTGCTG
	CATTCACAGTCGACCTACAGTGACTTCAGGCCCAGAACCAGATGCAGAGGGAACAGCC
	TGGCCTAGACTTCTCCACCAGCACCCACAATTGTGTAAGGCTGAAGCTCTATAATAAA
	TCTTTATTCTGTC
	ORF Start: ATG at 1	ORF Stop: TAG at 5737
	SEQ ID NO: 48	1912 aa	MW at 220299.6 Da
NOV10a,	MDLSDLGEAAAFLRRSEAELLLLQATALDGKKKCWIPDGENAYIEAEVKGSEDDGTVI
CG111455-01
Protein Sequence	VETADGQSLSIKEDKIQQMNPPEFEMIEDMAMLTHLNEASVLHTLKRRYGQWMIYTYS
	GLFCVTINPYKWLPVYQKEVMAAYKGKRRSEAPPHIFAVANNAFQDMLHSGESGAGKT
	VNSKHIIQYFATIAAMIESRKKGALEDQIMQANTILEAFGNAKTLRNDNSSRFGKFIR
	MHFGARGMLSSVDIDILLEKSRVIFQQAGERNYHIFYQILSGQKPTLDLLLVSANPSD
	FHFCSCGAVTVESLDDAEELLATEQAMDILGFLPDEKYGCYKLTGAIMHFGNMKFKQK
	PREEQLEADGTESADKAAFLMGINSSELVKCLIHPRIKVGNEYVTRGQTIEQVTCAVG
	ALSKSMYERMFKWLVARINRALDAKLSRQFFIGILDITGFEILEYNSLEQLCINFTNE
	KLQQFFNWHMFVLEQEEYKKESIEWVSIGFGLDLQACIDLIEKMPGILSILEEECMFP
	KATDLTFKTKLFDNHFGKSVHLQKPKPDKKKFEAHFELVHYAGVVPYNISGWLEKNKD
	LLNETVVAVFQKSSNRLLASLFENYMSTDSGEGEKKRKKGASFQTVASLHKENLNKLM
	TNLKSTAPHFVRCINPNVNKIPGKLDPYLVLQQLRCNGVLEGTRICREGFPNRLQYAD
	FKQRYCILNPRTFPKSKFVSSRKAAEELLGSLEIDHTQYRFGITKVFFKAGFLGQLEA
	IRDERLSKVFTLFQARAQGKLMRIKFQKILEERDALILIQWNIRAFMAVKNWPWMRLF
	FKIKPLVKSSEVGEEVAGLKEECAQLQKALEKSEFQREELKAKQVSLTQEKNDLILQL
	QAEQETLANVEEQCEWLIKSKIQLEARVKELSERVEEEEEINSELTARGRKLEDECFE
	LKKEIDDLETMLVKSEKEKRTTEHKVKNLTEEVEFLNEDISKLNRAAKVVQEAHQQTL
	DDLHMEEEKLSSLSKANLKLEQQVDLEGALEQERKARMNCERELHKLEGNLKLNRESM
	ENLESSQRHLAEELRKKELELSQMNSKVENEKGLVAQLQKTVKELQTQIKDLKEKLEA
	ERTTRAKMERERADLTQKLAKLNERLEEVGGSSLAQLEITKKQETKFQKLHRDMEEAT
	LHFETTSASLKKRHADSLAELEGQVENLQQVKQKLEKDKSDLQLEVKKLLTRVEQMTR
	AKANAEKLCTLYEERLHEATAKLDKVTQLANDLAAQKTKLWSESGEFLRRLEEKEALI
	NQLSREKSNFTRQIEDLRGQLEKETKSQSALAHALQKAQRDCDLLREQYEEEQEVKAE
	LHRTLSKVNAEMVQWRMKYENNVIQRTEDLEDAKKELAIRLQEAAEAMGVANARNASL
	ERARHQLQLELGDALSDLGKVRSAAARLDQKQLQSGKALADWKQKHEESQALLDASQK
	EVQALSTELLKLKNTYEESIVGQETLRRENKNLQEEISNLTNQVREGTKNLTEMEKVK
	KLIEEEKTEVQVTLEETEGALERNESKILHFQLELLEAKAELERKLSEKDEEIENFRR
	KQQCTIDSLQSSLDSEAKSRIEVTRLKKKMEEDLNEMELQLSCANRQVSEATKSLGQL
	QIQIKLLQMQLDDSTQLNSDLKEQVAVAERRNSLLQSELEDLRSLQEQTERGRRLSEE
	ELLEATERINLFYTQNTSLLSQKKKLEADVARMQKEAEEVVQECQNAEEKAKKAAIEA
	ANLSEELKKKQDTIAHLERTRENMEQTITDLQKRLAEAEQMALMGSRKQIQKLESRVR
	ELEGELEGEIRRSAEAQRGARRLERCIKELTYQAEEDKKNLSRMQTQMDKLQLKVQNY
	KQQVEVAETQANQYLSKYKKQQHELNEVKERAEVAESQVNKLKIKAREFGKKVQEE

[0369] Further analysis of the NOV10a protein yielded the following properties shown in Table 10B.

TABLE 10B
Protein Sequence Properties NOV10a
PSort     0.9800 probability located in nucleus; 0.3000 probability
analysis: located in microbody (peroxisome); 0.1000 probability located
          in mitochondrial matrix space; 0.1000 probability located in
          lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0370] A search of the NOV10a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 10C.

TABLE 10C
Geneseq Results for NOV10a
		NOV10a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAW54241	Rattus norvegicus mutant alpha-	3 . . . 1908	1152/1928 (59%)	0.0
	myosin heavy chain - Rattus	6 . . . 1879	1496/1928 (76%)
	norvegicus, 1886 aa. [WO9813476-
	A1, 02 APR. 1998]
ABG21233	Novel human diagnostic protein	2 . . . 1912	1137/1940 (58%)	0.0
	#21224 - Homo sapiens, 1948 aa.	9 . . . 1947	1522/1940 (77%)
	[WO200175067-A2, 11 OCT. 2001]
ABG21233	Novel human diagnostic protein	2 . . . 1912	1137/1940 (58%)	0.0
	#21224 - Homo sapiens, 1948 aa.	9 . . . 1947	1522/1940 (77%)
	[WO200175067-A2, 11 OCT. 2001]
ABB71125	Drosophila melanogaster	24 . . . 1903	905/2006 (45%)	0.0
	polypeptide SEQ ID NO 40167 -	28 . . . 2029	1304/2006 (64%)
	Drosophila melanogaster, 2067 aa.
	[WO200171042-A2, 27 SEP. 2001]
AAM41000	Human polypeptide SEQ ID NO	31 . . . 1906	705/1908 (36%)	0.0
	5931 - Homo sapiens, 1988 aa.	44 . . . 1944	1104/1908 (56%)
	[WO200153312-A1, 26 JUL. 2001]

[0371] In a BLAST search of public sequence datbases, the NOV10a protein was found to have homology to the proteins shown in the BLASTP data in Table 10D.

TABLE 10D
Public BLASTP Results for NOV10a
		NOV10a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9IBD4	Myosin heavy chain - Gallus gallus	1 . . . 1912	1362/1936 (70%)	0.0
	(Chicken), 1937 aa.	2 . . . 1936	1647/1936 (84%)
Q8UWA0	Myosin heavy chain - Gallus gallus	1 . . . 1904	1252/1932 (64%)	0.0
	(Chicken), 1941 aa.	4 . . . 1934	1575/1932 (80%)
P13533	Myosin heavy chain, cardiac	3 . . . 1908	1197/1928 (62%)	0.0
	muscle alpha isoform (MyHC-	6 . . . 1932	1549/1928 (80%)
	alpha) - Homo sapiens (Human),
	1939 aa.
Q02566	Myosin heavy chain, cardiac	3 . . . 1912	1202/1933 (62%)	0.0
	muscle alpha isoform (MyHC-	6 . . . 1937	1547/1933 (79%)
	alpha) - Mus musculus (Mouse),
	1938 aa.
P02563	Myosin heavy chain, cardiac	3 . . . 1908	1200/1928 (62%)	0.0
	muscle alpha isoform (MyHC-	6 . . . 1931	1545/1928 (79%)
	alpha) - Rattus norvegicus (Rat),
	1938 aa.

[0372] PFam analysis predicts that the NOV10a protein contains the domains shown in the Table 10E.

TABLE 10E
Domain Analysis of NOV10a
		Identities/
	NOV10a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
Myosin_N	31 . . . 75	17/48 (35%)	1.4e−13
		40/48 (83%)
myosin_head	85 . . . 745	357/735 (49%)	0
		577/735 (79%)
Myosin_tail	1046 . . . 1905	427/864 (49%)	1.6e−301
		669/864 (77%)

Example 11

[0373] The NOV11 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 11A.

TABLE 11A
NOV11 Sequence Analysis
	SEQ ID NO:49	757 bp
NOV11a,	AGCTCCGCTCCATAGCCTTCTCCAGGGCTGTGTTCGCAGACTTCCTGGCCACACTCCT
CG112292-02 DNA	CTTCGTCTTCTTTGGCCTCGGCTCTGCCCTCAACTGGCCACAGGCCCTGCCCTCTGTG
Sequence	CTACAGATTGCCATGGCGTTTGGCTTGGGTATTGGCACCCTGGTACAGGCTCTGGGCC
	ACATAAGCGGGGCCCACATCAACCCTGCCGTGACTGTGGCCTGCCTGGTGGGCTGCCA
	CGTCTCCGTTCTCCGAGCCGCCTTCTACGTGGCTGCCCAGCTGCTGGGGGCTGTGGCC
	GGAGCCGCTCTGCTCCATGAGATCACGCCAGCAGACATCCGCGGGGACCTGGCTGTCA
	ATGCTCTCAGCAACAGCACGACGGCTGGCCAGGCGGTGACTGTGGAGCTCTTCCTGAC
	ACTGCAGCTGGTGCTCTGCATCTTCGCCTCCACCGATGAGCGCCGCGGAGACAACCCG
	GGCACCCCTGCTCTCTCCATAGGCTTCTCCGTGGCCCTGGGCCACCTCCTTGGGATCC
	ATTACACCGGCTGCTCTATGAATCCTGCCCGCTCCCTGGCCCCAGCTGTCGTCACTGG
	CAAATTTGATGACCACTGGCCAAGAGCCTGTCGGAGCGCCTGGCAGTGCTGAAGGGCC
	TGGAGCCGGACACCGATTGGGAGGAGCGCGAGGTGCGACGGCGGCAGTCGGTGGAGCT
	GCACTCGCCGCAGAGCCTGCCACGGGGTACCAAGGCCTGACTGCAGCCAAGCTAATTC
	CGG
	ORF Start: ATG at 129		ORF Stop: TGA at 630
	SEQ ID NO:50	167 aa	MW at 17214.7 Da
NOV11a,	MAFGLGIGTLVQALGHISGAHINPAVTVACLVGCHVSVLRAAFYVAAQLLGAVAGAAL
CG112292-02	LHEITPADIRGDLAVNALSNSTTAGQAVTVELFLTLQLVLCIFASTDERRGENPGTPA
Protein Sequence	LSIGFSVALGHLLGIHYTGCSMNPARSLAPAVVTGKFDDHWPRACRSAWQC
	SEQ ID NO:51	849 bp
NOV11b,	AGTGCGAGAGCGAGTGCCCGGAGCATCCTGGCCCTGAGACAGCTGGGCCAGCCCCGCA
CG11292-04 DNA	GGGCTCTGCAGCATGTGGGAGCTCCGCTCCATAGCCTTCTCCAGGGCTGTGTTCGCAG
Sequence	AGTTCCTGGCCACACTCCTCTTCGTCTTCTTTGGCCTCGGCTCTGCCCTCAACTGGCC
	ACAGGCCCTGCCCTCTGTGCTACAGATTGCCATGGCGTTTGGCTTGGGTATTGGCACC
	CTGGTACAGGCTCTGGGCCACATAAGCAGGGCCCACATCAACCCTGCCGTGACTGTGG
	CCTGCCTGGTGGGCTGCCACGTCTCCGTTCTCCGAGCCGCCTTCTACGTGGCTGCCCA
	GCTGCTGGGGGCTGTGGCCGGAGCCGCTCTGCTCCATGAGATCACGCCAGCAGACATC
	CGCGGGGACCTGGCTGTCAATGCTCTCAGCAACAGCACGACGGCTGGCCAGGCGGTGA
	CTGTGGAGCTCTTCCTGACACTGCAGCTGATGCTCTGCATCTTCGCCTCCACCGATGA
	GCGCCGCGGAGAGAACCCGGGCACCCCTGCTCTCTCCATAGGCTTCTCCGTGGCCCTG
	GGCTCCCTCCTCTACAACTACGTGCTGTTTCCGCCAGCCAAGAGCCTGTCGGAGCGCC
	TGGCAGTGCTGAAGGGCCTGGAGCCGGACACCGATTGGGAGGAGCGCGAGGTGCGACG
	GCGGCAGTCGGTGGAGCTGCACTCGCCGCAGAGCCTGCCACGGGGTACCAAGGCCTGA
	GGGCCGCCAGCGGCCTCTAAGGCCCCGACGGACGCTTGTGAGGCCCGAGGCAGAAGGG
	CCCACCCCGTCCCTCCTCTCCCGCAGGTCTGAAGTTG
	ORF Start: ATG at 71		ORF Stop: TGA at 752
	SEQ ID NO:52	227 aa	MW at 24267.8 Da
NOV11b,	MWELRSIAFSRAVFAEFLATLLFVFFGLGSALNWPQALPSVLQIAMAFGLGIGTLVQA
CG112292-04	LGHISRAHINPAVTVACLVGCHVSVLRAAFYVAAQLLGAVAGAALLHEITPADIRGDL
Protein Sequence	AVNALSNSTTAGQAVTVELFLTLQLMLCIFASTDERRGENPGTPALSIGFSVALGSLL
	YNYVTLFPPAKSLSERLAVLKGLEPDTDWEEREVRRRQSVELHSPQSLPRGTKA
	SEQ ID NO:53	572 bp
NOV11c,	GCCCTTATGTGGGAGCTCCGCTCCATAGCCTTCTCCAGGGCTGTGTTCGCAGAGTTCC
CG112292-05 DNA	TGGCCACACTCCTCTTCGTCTTCTTTGGCCTCGGCTCTGCCCTCAACTGGCCACAGGC
Sequence	CCTGCCCTCTGTGCTACAGATTGCCATGGCGTTTGGCTTGGGTATTGGCACCCTGGGC
	CACCTCCTTGGGATCCATTACACCGGCTGCTCTATGAATCCTGCCCGCTGGGTGGCTC
	CAGCTGTCGTCACTGGCAAATTTGATGACCACTGGGTCTTCTGGATCGGACCCCTGGT
	GGGCGCCATCCTGGGCTCCCTCCTCTACAACTACGTGCTGTTTCCGCCAGCCAAGAGC
	CTGTCGGAGCGCCTGGCAGTGCTGAAGGGCCTGGAGCCGGACACCGATTGGGAGGAGC
	GCGAGGTGCGACGGCGGCAGTCGGTGGAGCTGCACTCGCCGCAGAGCCTGCCACGGGG
	TACCAAGGCCTGAGGGCCGCCAGCGGCCTCTAAGGCCCCGACGGACGCTTGTGAGGCC
	CGAGGCAGAAGGGCCCACCCCGTCCCTCCTCTCCCGCAGGTCTGAAGTTG
	ORF Start: ATG at 7		ORF Stop: TGA at 475
	SEQ ID NO:54	156 aa	MW at 17194.8 Da
NOV11c,	MWELRSIAFSRAVFAEFLATLLFVFFGLGSALNWPQALPSVLQIAMAFGLGIGTLGHL
CG112292-05	LGIHYTGCSMNPARSLAPAVVTGKFDDHWVFWIGPLVGAILGSLLYNYVLFPPAKSLS
Protein Sequence	ERLAVLKGLEPDTDWEEREVRRRQSVELHSPQSLPRGTKA

[0374] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 11B.

TABLE 11B
Comparison of NOV11a against NOV11b and NOV11c.
	NOV11a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV11b	1 . . . 145	116/145 (80%)
	46 . . . 187	119/145 (82%)
NOV11c	136 . . . 157	22/22 (100%)
	66 . . . 87	22/22 (100%)

[0375] Further analysis of the NOV11a protein yielded the following properties shown in Table 11C.

TABLE 11C
PSort     0.6000 probability located in plasma membrane; 0.4000
analysis: probability located in Golgi body; 0.3000 probability located
          in endoplasmic reticulum (membrane); 0.1000 probability
          located in mitochondrial inner membrane
SignalP   Cleavage site between residues 66 and 67
analysis:

[0376] A search of the NOV11a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 11D.

TABLE 11D
Geneseq Results for NOV11a
		NOV11a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAR51070	A water channel protein localized in	1 . . . 157	140/157 (89%)	2e−77
	the rat kidney collecting tubule -	46 . . . 202	150/157 (95%)
	Rattus sp. (Sprague-Dawley), 271 aa.
	[EP591789-A, 13 APR. 1994]
AAR25424	Human MIP - Homo sapiens, 263 aa.	1 . . . 157	101/157 (64%)	2e−54
	[U.S. Pat. No. 7693291-N, 25 FEB. 1992]	46 . . . 202	127/157 (80%)
AAW94319	Rat aquaporin-5 - Rattus sp, 265 aa.	1 . . . 157	102/158 (64%)	6e−54
	[U.S. Pat. No. 5858702-A, 12 JAN. 1999]	47 . . . 204	126/158 (79%)
AAW55787	Rat aquaporin-5 - Rattus sp, 265 aa.	1 . . . 157	102/158 (64%)	6e−54
	[U.S. Pat. No. 5741671-A, 21 APR. 1998]	47 . . . 204	126/158 (79%)
ABB57089	Mouse ischaemic condition related	1 . . . 157	82/157 (52%)	5e−43
	protein sequence SEQ ID NO: 194 -	52 . . . 208	109/157 (69%)
	Mus musculus, 300 aa.
	[WO200188188-A2, 22 NOV. 2001]

[0377] In a BLAST search of public sequence datbases, the NOV11a protein was found to have homology to the proteins shown in the BLASTP data in Table 11E.

TABLE 11E
Public BLASTP Results for NOV11a
		NOV11a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P41181	Aquaporin-CD (AQP-CD) (Water	1 . . . 157	157/157 (100%)	2e−85
	channel protein for renal collecting	46 . . . 202	157/157 (100%)
	duct) (ADH water channel) (Aquaporin
	2) (Collecting duct water channel
	protein) (WCH-CD) - Homo sapiens
	(Human), 271 aa.
Q9UD68	HAQP-CD = COLLECTING duct	1 . . . 157	156/157 (99%)	7e−85
	aquaporin - Homo sapiens (Human),	46 . . . 202	156/157 (99%)
	271 aa.
I64818	water-channel aquaporin 2 - human,	1 . . . 157	156/157 (99%)	2e−84
	271 aa.	46 . . . 202	156/157 (99%)
Q8VCG5	Aquaporin 2 - Mus musculus (Mouse),	1 . . . 157	140/157 (89%)	5e−77
	271 aa.	46 . . . 202	150/157 (95%)
Q9R232	Aquaporin 2 (Aquaporin-2) - Mus	1 . . . 157	140/157 (89%)	5e−77
	musculus (Mouse), 271 aa.	46 . . . 202	150/157 (95%)

[0378] PFam analysis predicts that the NOV11a protein contains the domains shown in the Table 11F.

TABLE 11F
Domain Analysis of NOV11a
		Identities/
	NOV11a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
MIP	1 . . . 157	88/197 (45%)	5.9e−91
		152/197 (77%)

Example 12

[0379] The NOV12 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 12A.

TABLE 12A
NOV12 Sequence Analysis
	SEQ ID NO:55	1081 bp
NOV12a,	AAAATACAATATACTAGCATGCACAACCGGTTCCCCCAAACATGGAGTCCTGCAGCCC
CG112722-01 DNA	AGTTCTTACCTGAATCAGGATGGAGGGTGTGGTGGGTCCAAGTGGAGCTGTTGGCCAT
Sequence	GTGCCTACTTGCTGCGTACCTGCAGATCCCACTCCCTCAGGTCTCCCTGGCCCTTCAC
	TCTTGGAAGTCTTCAGGCAAATTTTTCACTTACGAGGGACTGCATATATTCTACCAAG
	ACTCTGTGGGTGTGGTTGGAAGTCTGGAGATAGCTGTGCTTTTACACAGCCTTCCAAC
	ATCCAGCTATGATTGGTACAAGATTTGGGAAGGTCTGACCTTGAGGTTTCATCAAGTT
	CTTGTGCTTGATTTCTTAGGCTTTGGCTTCAGTGACAATCCACAACCACATCACTATT
	CCATATTTGAGCAGGCCAGCATTATGGAAGTGCTTTTGTGGCATCTGGGGCTCCAGAA
	CCACAGGACCAACCTTTTGTCTCATGACTATGGAGATATTGTTGCTCAGGAGCTCCTC
	TACCAGTACAAGCAGAATCAATCTGGTAGGCTTACCATAAAGAGTATCCATCTGTCAA
	ATGGAGGTATCTTTCCTGAGACTCACCGTCCACTCCTTCTCCAAAAGATACTCAAAGA
	TGGAGGTGTGCTGTCACCCATCCTCACGTGGCTGATGAACTTCTTTGTATTCTCGCGA
	TGTCTCACCCCAGTCTTTGGGCCATGTACTTGGCCCTCTGAGAGTGAGCTGTCGGATA
	TGTGGGCAGTCCCATCCCACAGCTGCAACAATGATGGGAACTTAGTCATTGTCAATCT
	CTTACAGTACATCATCAATCAGAGAGAGAAGTTTAGAAGACACCGAGTGGGAGCTCTT
	GCCTCTGAAACTAACCCCATTGATTTTATCTATGAGCCACTGGATCCTGTAAATCCCT
	ATCCACAGTTTTTCGAGCTGTACAGGAAAATGCTGTCACGGTCCATGATGTCAATTCT
	GGATGACCACATTAGCCACGATCCACAGCTAGAGGATCCCATGGGCTTCCTGAATGCA
	TACCTGGGCTTCATCAAGTCCTTTTGAGTTGGAAAGA
	ORF Start: ATG at 19		ORF Stop: TGA at 1069
	SEQ ID NO:56	350 aa	MW at 40530.2 Da
NOV12a,	MHNRFPQTWSPAAQFLPESGWRVWWVQVELLAMCLLAAYLQI PLPQVSLALHSWKSSG
CG112722-01	KFFTYEGLHIFYQDSVGVVGSLEIAVLLHSLPTSSYDWYKIWEGLTLRFHQVLVLDFL
Protein Sequence	QSGRLTIKSIHLSNGGIFPETHRPLLLQKILKDGGVLSPILTWLMNFFVESRCLTPVF
	QSGRLTIKSIHLSNGGIFPETHRPLLLQKILKDGGVLSPILTWLMNFFVFSRCLTPVF
	GPCTWPSESELWDMWAVPSHSCNNDGNLVIVNLLQYIINQREKFRRHRVGALASETNP
	IDFIYEPLDPVNPYPEFFELYRKMLSRSMMSILDDHISHDPQLEDPMGFLNAYLGFIK
	SF

[0380] Further analysis of the NOV12a protein yielded the following properties shown in Table 12B.

TABLE 12B
Protein Sequence Properties NOV12a
PSort     0.6400 probability located in microbody (peroxisome); 0.6000
analysis: probability located in endoplasmic reticulum (membrane);
          0.1000 probability located in mitochondrial inner membrane;
          0.1000 probability located in plasma membrane
SignalP   Cleavage site between residues 51 and 52
analysis:

[0381] A search of the NOV12a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 12C.

TABLE 12C
Geneseq Results for NOV12a
		NOV12a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM23929	Human EST encoded protein SEQ ID	22 . . . 350	272/329 (82%)	e−154
	NO: 1454 - Homo sapiens, 326 aa.	2 . . . 326	287/329 (86%)
	[WO200154477-A2, 02 AUG. 2001]
AAB58910	Breast and ovarian cancer associated	22 . . . 350	272/329 (82%)	e−154
	antigen protein sequence SEQ ID 618 -	4 . . . 328	287/329 (86%)
	Homo sapiens, 328 aa.
	[WO200055173-A1, 21 SEP. 2000]
ABB57057	Mouse ischaemic condition related	22 . . . 350	268/329 (81%)	e−152
	protein sequence SEQ ID NO: 109 -	11 . . . 335	287/329 (86%)
	Mus musculus, 335 aa.
	[WO200188188-A2, 22 NOV. 2001]
ABG07229	Novel human diagnostic protein	296 . . . 350	48/63 (76%)	5e−19
	#7220 - Homo sapiens, 151 aa.	89 . . . 151	51/63 (80%)
	[WO200175067-A2, 11 OCT. 2001]
ABG07229	Novel human diagnostic protein	296 . . . 350	48/63 (76%)	5e−19
	#7220 - Homo sapiens, 151 aa.	89 . . . 151	51/63 (80%)
	[WO200175067-A2, 11 OCT. 2001]

[0382] In a BLAST search of public sequence datbases, the NOV12a protein was found to have homology to the proteins shown in the BLASTP data in Table 12D.

TABLE 12D
Public BLASTP Results for NOV12a
		NOV12a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O15007	PEG1/MEST protein (Mesoderm	22 . . . 350	272/329 (82%)	e−153
	specific transcript (Mouse) homolog)	11 . . . 335	287/329 (86%)
	(Hypothetical 38.8 kDa protein)
	(Unknown) (Protein for MGC:20321) -
	Homo sapiens (Human), 335 aa.
O14973	PEG1/MEST protein - Homo sapiens	22 . . . 350	271/329 (82%)	e−152
	(Human), 335 aa.	11 . . . 335	286/329 (86%)
Q92571	MEST protein - Homo sapiens	22 . . . 350	270/329 (82%)	e−152
	(Human), 335 aa.	11 . . . 335	286/329 (86%)
Q07646	PEG1/MEST protein (Mesoderm	22 . . . 350	268/329 (81%)	e−151
	specific transcript) - Mus musculus	11 . . . 335	287/329 (86%)
	(Mouse), 335 aa.
Q9IB18	Epoxide hydrolase (EC 3.3.2.3) -	22 . . . 350	204/329 (62%)	e−118
	Brachydanio rerio (Zebrafish) (Zebra	20 . . . 344	250/329 (75%)
	danio), 344 aa.

[0383] PFam analysis predicts that the NOV12a protein contains the domains shown in the Table 12E.

TABLE 12E
Domain Analysis of NOV12a
		Identities/
	NOV12a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
abhydrolase	108 . . . 347	43/252 (17%)	0.013
		159/252 (63%)

Example 13

[0384] The NOV13 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 13A.

TABLE 13A
NOV13 Sequence Analysis
	SEQ ID NO:57	2195 bp
NOV13a,	ACCCCAGGCAGCAGCGAGTGACAGGACGTCTGGACCGGCGCGCCGCTAGCAGCTCTGC
CG112881-02 DNA	CGGGCCGCGGCGGTGATCGATGGGGAGCGGCTGGAGCGGACCCAGCGAGTGAGGGCGC
Sequence	ACAGCCGGGACGCCGAGGCGGCGGGCGGGAGACCCGCACCAGCGCAGCCGGCCCTCGG
	CGGGACGTGACGCAGCGCCCGGGGCGCGGGTTTGATATTTGACAAATTGATCTAAAAT
	GGCTGGGTTTTTATCTGAATAACTCACTGATGCCATCCCAGAAAGTCCGCACCAGGTG
	TATTTGATATAGTGTTTGCAACAAATTCGACCCAGGTGATCAAAATGATTCTCAACTC
	TTCTACTGAAGATGGTATTAAAAGAATCCAAGATGATTGTCCCAAAGCTGGAAGGCAT
	AATTACATATTTGTCATGATTCCTACTTTATACAGTATCATCTTTGTGGTGGGAATAT
	TTGGAACAGCTTGGTGGTGATAGTCATTTACTTTTATATGAAGCTGAAGACTGTGGC
	CAGTGTTTTTCTTTTGAATTTAGCACTGGCTGACTTATGCTTTTTACTGACTTTGCCA
	CTATGGGCTGTCTACACAGCGTCAGTTTCAACCTGTACGCTAGTGTGTTTCTACTCAC
	GTGTCTCAGCATTGTTCACCCAATGAAGTCCCGCCTTCGACGCACAATGCTTGTAGCC
	AAAGTCACCTGCATCATCATTTGGCTGCTGGCAGGCTTGGCCAGTTTGCCAGCTATAA
	TCCATCGAAATGTATTTTTCATTGAGAACACCAATATTACAGTTTGTGCTTTCCATTA
	TGAGTCCCAAAATTCAACCCTTCCGATAGGGCTGGGCCTGACCAAAAATATACTGGGT
	TTCCTGTTTCCTTTTCTGATCATTCTTACAAGTTATACTCTTATTTGGAAGGCCCTAA
	AGAAGGCTTATGAAATTCAGAAGAACAAACCAAGAAATGATGATATTTTTAAGATAAT
	TATGGCAATTGTGCTTTTCTTTTTCTTTTCCTGCATTCCCCACCAAATATTCACTTTT
	CTGGATGTATTGATTCAACTAGGCATCATACGTGACTGTAGAATTGCAGATATTGTGG
	ACACGGCCATGCCTATCACCATTTGTATAGCTTATTTTAACAATTGCCTGAATCCTCT
	TTTTTATGGCTTTCTGGGGAAAAAATTTAAAAGATATTTTCTCCAGCTTCTAAAATAT
	ATTCCCCCAAAAGCCAAATCCCACTCAAACCTTTCAACAAAAATGAGCACGCTTTCCT
	ACCGCCCCTCAGATAATGTAAGCTCATCCACCAAGAAGCCTGCACCATGTTTTGAGGT
	TGAGTGACATGTTCGAAACCTGTCCATAAAGTAATTTTGTGAAAGAAGGAGCAAGAGA
	ACATTCCTCTGCAGCACTTCACTACCAAATGAGCATTAGCTACTTTTCAGAATTGAAG
	GAGAAAATGCATTATGTGGACTGAACCGACTTTTCTAAAGCTCTGAACAAAAGCTTTT
	CTTTCCTTTTGCAACAAGACAAAGCAAAGCCACATTTTGCATTAGACAGATGACGGCT
	GCTCGAAGAACAATGTCAGAAACTCGATGAATGTGTTGATTTGAGAAATTTTACTGAC
	AGAAATGCAATCTCCCTAGCCTGCTTTTGTCCTGTTATTTTTTATTTCCACATAAAGG
	TATTTAGAATATATTAAATCGTTAGAGGAGCAACAGGAGATGAGAGTTCCAGATTGTT
	CTGTCCAGTTTCCAAAGGGCAGTAAAGTTTTCGTGCCGGTTTTCAGCTATTAGCAACT
	GTGCTACACTTGCACCTGGTACTGCACATTTTGTACAAAGATATGCTAAGCAGTAGTC
	GTCAAGTTGCAGATCTTTTTGTGAAATTCAACCTGTGTCTTATAGGTTTACACTCCCA
	AAACAATGCCCGTAAGATGGCTTATTTGTATAATGGTGTTACTAAAGTCACATATAAA
	AGTTAAACTACTTGTAAAGGTGCTGCACTGGTCCCAAGTAGTAGTGTCCTCCTAGTAT
	ATTAGTTTGATTTAATATCTGAGAAGTGTATATAGTTTGTGGTAAAAAGATTATATAT
	CATAAAGTATGCCTTCCTGTTTAAAAAAAGTATATATTCTACACATATATATATATGT
	ATATCTATATCTCTAAACTGCTGTTAATTGATTAAAATCTGGCAAAGTT
	ORF Start: ATG at 559		ORF Stop: TGA at 1339
	SEQ ID NO:58	260 aa	MW at 29763.1 Da
NOV 13a,	MLFTDFATMGCLHSVSFNLYASVFLLTCLSIVHPMKSRLRRTMLVAKVTCIIIWLLAG
CG112881-02	LASLPAIIHRNVFFIENTNITVCAFHYESQNSTLPIGLGLTKNILGFLFPFLIILTSY
Protein Sequence	TLIWKALKKAYEIQKNKPRNDDIFKIIMAIVLFFFFSWIPHQIFTFLDVLIQLGIIRD
	CRIADIVDTAMPITICIAYFNNCLNPLFYGFLGKKFKRYFLQLLKYIPPKAKSHSNLS
	TKMSTLSYRPSDNVSSSTKKPAPCFEVE

[0385] Further analysis of the NOV13a protein yielded the following properties shown in Table 13B.

TABLE 13B
Protein Sequence Properties NOV13a
PSort     0.6000 probability located in plasma membrane; 0.4000
analysis: probability located in Golgi body; 0.3548 probability
          located in mitochondrial inner membrane; 0.3131 probability
          located in mitochondrial intermembrane space
SignalP   Cleavage site between residues 62 and 63
analysis:

[0386] A search of the NOV13a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 13C.

TABLE 13C
Geneseq Results for NOV13a
		NOV13a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU78654	Human Angiotensin receptor 1,	14 . . . 260	247/253 (97%)	e−140
	AGTR1 - Homo sapiens, 359 aa.	107 . . . 359	247/253 (97%)
	[EP1184456-A2, 06 MAR. 2002]
AAB02844	Human G protein coupled receptor	14 . . . 260	247/253 (97%)	e−140
	AT1 protein SEQ ID NO: 66 - Homo	107 . . . 359	247/253 (97%)
	sapiens, 359 aa. [WO200022131-A2,
	20 APR. 2000]
AAU78656	Human Angiotensin receptor 1,	14 . . . 260	246/253 (97%)	e−139
	AGTR1, variant #2 - Homo sapiens,	107 . . . 359	246/253 (97%)
	359 aa. [EP1184456-A2, 06 MAR. 2002]
AAU78655	Human Angiotensin receptor 1,	14 . . . 260	246/253 (97%)	e−139
	AGTR1, variant #1 - Homo sapiens,	107 . . . 359	246/253 (97%)
	359 aa. [EP1184456-A2, 06 MAR. 2002]
AAB02849	Human G protein coupled receptor	14 . . . 260	246/253 (97%)	e−139
	hAT1 mutant protein SEQ ID NO: 94 -	107 . . . 359	246/253 (97%)
	Homo sapiens, 359 aa.
	[WO200022131-A2, 20 APR. 2000]

[0387] In a BLAST search of public sequence datbases, the NOV13a protein was found to have homology to the proteins shown in the BLASTP data in Table 13D.

TABLE 13D
Public BLASTP Results for NOV13a
		NOV13a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P30556	Type-1 angiotensin II receptor	14 . . . 260	247/253 (97%)	e−140
	(AT1) (AT1AR) - Homo sapiens	107 . . . 359	247/253 (97%)
	(Human), 359 aa.
Q9GLN9	Angiotensin II type-1 receptor -	14 . . . 260	246/253 (97%)	e−139
	Pan troglodytes (Chimpanzee), 359 aa.	107 . . . 359	247/253 (97%)
Q8TBK4	Angiotensin receptor 1 - Homo	14 . . . 260	245/253 (96%)	e−138
	sapiens (Human), 359 aa.	107 . . . 359	246/253 (96%)
P34976	Type-1 angiotensin II receptor	14 . . . 260	241/253 (95%)	e−137
	(AT1) - Oryctolagus cuniculus	107 . . . 359	245/253 (96%)
	(Rabbit), 359 aa.
Q9WV26	Type-1 angiotensin II receptor	14 . . . 260	234/253 (92%)	e−134
	(AT1) - Cavia porcellus (Guinea	107 . . . 359	242/253 (95%)
	pig), 359 aa.

[0388] PFam analysis predicts that the NOV13a protein contains the domains shown in the Table 13E.

TABLE 13E
Domain Analysis of NOV13a
		Identities/
	NOV13a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
7tm_1	14 . . . 203	69/209 (33%)	1.9e−54
		162/209 (78%)

Example 14

[0389] The NOV14 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 14A.

TABLE 14A
NOV14 Sequence Analysis
	SEQ ID NO:59	5451 bp
NOV14a,	ACCTTTCCATTCAGTCGCCCAACATGGCTGGAGCGCGGCGGAGGTGAGCCGGCCGCCC
CG113803-01 DNA	GCCCGCAGACGCCCCAGCCTACTGCGCCCGAGTCCCGCGGCCCCAGTGGCGCCTCAGC
Sequence	TCTCCGGTGCCGAGGCCCAACGGCTCGATCGCTGCCCGCCGCCAGCATGTTGGGCGCC
	CCGGACGAGAGCTCCGTGCGGGTGGCTGTCAGAATAAGACCACAGCTTGCCAAAGAGA
	AGATTGAAGGATGCCATATTTGTACATCTGTCACACCAGGAGAGCCTCAGGTCTTCCT
	AGGGAAAGATAAGGCTTTTACTTTTGACTATGTATTTGACATTGACTCCCAGCAAGAG
	CAGATCTACATTCAATGTATAGAAAAACTAATTGAAGGTTGCTTTGAAGGATACAATG
	CTACAGTTTTTGCTTATGGACAAACTCGAGCTGGTAAAACATACACAATGGGAACAGG
	ATTTGATGTTAACATTGTTGAGGAAGAACTGGGTATTATTTCTCGAGCTGTTAAACAC
	CTTTTTAAGAGTATTGAAGAAAAAAAACACATAGCAATTAAAAATGGGCTCCCTGCTC
	CAGATTTTAAAGTGAATGCCCAATTCTTAGAGCTCTATAATGAAGAGGTCCTTGACTT
	ATTTGATACCACTCGTGATATTGATGCAAAAAGTAAAAAATCAAATATAAGAATTCAT
	GAAGATTCAACTGGAGGAATTTATACTGTGGGCGTTACAACACGTACTGTGAATACAG
	AATCAGAGATGATGCAGTGTTTGAAGTTGGGTGCTTTATCCCGGACAACTGCCAGTAC
	CCAGATGAATGTTCAGAGCTCTCGTTCACATGCCATTTTTACCATTCATGTGTGTCAA
	ACCAGAGTGTGTCCCCAAATAGATGCTGACAATGCAACTGATAATAAAATTATTTCTG
	AATCAGCACAGATGAATGAATTTGAAACCCTGACTGCAAAGTTCCATTTTGTTGATCT
	CGCAGGATCTGAAAGACTGAAGCGTACTGGAGCTACAGGCGAGAGGGCAAAAGAAGGC
	ATTTCTATCAACTGTGGACTTTTGGCACTTGGCAATGTAATAAGTGCCTTGGGAGACA
	AGAGCAAGAGGGCCACACATGTCCCCTATAGAGATTCCAAGCTAACAACACTACTACA
	GGATTCCCTCGGGGGTAATAGCCAAACAATCATGATAGCATGTGTCAGCCCTTCAGAC
	AGAGACTTTATGGAAACGTTAAACACCCTCAAATACGCCAATCGAGCTAGAAATATCA
	AGAATAAGGTGATGGTCAATCAGGACAGAGCTAGTCAGCAAATCAATGCACTTCGTAG
	TGAAATCACACGACTTCAGATGGAGCTCATGGAGTACAAAACAGGTAAAAGAATAATT
	GACGAAGAGGGTGTGGAAAGCATCAATGACATGTTTCATGAGAATGCTATGCTACAGA
	CTGAAAATAATAACCTGCGTGTAAGAATTAAAGCCATGCAAGAGACGGTTGATGCATT
	GAGGTCCAGAATTACACAGCTTGTTAGTGATCAGGCCAACCATGTTCTTGCCAGAGCA
	GGTGAAGGAAATGAGGAGATTAGTAATATGATTCATAGTTATATAAAAGAAATCGAAG
	ATCTCAGGGCAAAATTATTAGAAAGTGAAGCAGTGAATGAGAACCTTCGAAAAAACTT
	GACAAGAGCCACAGCAAGAGCGCCATATTTCAGCGGATCATCAACTTTTTCTCCTACC
	ATACTATCCTCAGACAAAGAAACCATTGAAATTATAGACCTAGCAAAAAAAGATTTAG
	AGAAGTTGAAAAAAAAAAAAAAGAGGAAGAAAAAAAGTGTGGCTGGTAAAGAGGATAA
	TACAGACACTGAGCAAGAGAAGAAAGAAGAAAAGGGTGTTTCGGAAAGAGAAAACAAT
	GAATTAGAAGTGGAAGAAAGTCAAGAAGTGAGTGATCATGAGGATGAAGAAGAGGAGG
	AGGAGGAGGAGGAAGATGACATTGATGGGGGTGAAAGTTCTGATGAATCACATTCTGA
	ATCAGATGAAAAAGCCAATTATCAAGCAGACTTGGCAAACATTACTTGTGAAATTGCA
	ATTAAGCAAAAGCTGATTGATGAACTAGAAAACAGCCAGAAAAGACTCCAGACTCTGA
	AAAAGCAGTATGAAGAGAAGCTAATGATGCTGCAACATAAAATTCGGGATACTCAGCT
	TGAAAGAGACCAGGTGCTTCAAAACTTAGGCTCGGTAGAATCTTACTCAGAAGAAAAA
	GCAAAAAAAGTTAGGTCTGAATATGAAAAGAAACTCCAAGCCATGAACAAACAACTGC
	AGAGACTTCAAGCAGCTCAAAAAGAACATGCAAGGTTGCTTAAAAATCAGTCTCAGTA
	TGAAAAGCAATTGAAGAAATTGCAGCAGGATGTGATGGAAATGAAAAAAACAAAGGTT
	CGCCTAATGAAACAAATGAAAGAAGAACAAGAGAAAGCCAGACTGACTGAGTCTAGAA
	GAAACAGAGAGATTGCTCAGTTGAAAAAGGATCAACGTAAAAGAGATCATCAACTTAG
	ACTTCTGCAAGCCCAAAAAAGAAACCAAGAAGTGGTTCTACGTCGCAAAACTGAAGAG
	GTTACGGCTCTTCGTCGGCAAGTAAGACCCATGTCAGATAAAGTGGCTGGGAAAGTTA
	CTCGGAAGCTGAGTTCATCTGATGCACCTGCTCAGGACACAGGTTCCAGTGCAGCTGC
	TGTCGAAACAGATGCATCAAGGACAGGAGCCCAGCAGAAAATGAGAATTCCTGTGGCG
	AGAGTCCAGGCCTTACCAACGCCGGCAACAAATGGAAACAGGAAAAAATATCAGAGGA
	AAGGATTGACTGGCCGAGTGTTTATTTCCAAGACAGCTCGCATGAAGTGGCAGCTCCT
	TGAGCGCAGGGTCACAGACATCATCATGCAGAAGATGACCATTTCCAACATGGAGGCA
	GATATCAATAGACTCCTCAAGCAACGGGAGGAACTCACAAAAAGACGAGAGAAACTTT
	CAAAAAGAAGGGAGAAGATAGTCAAGGAGAATGGAGAGGGAGATAAAAATGTGGCTAA
	TATCAATGAAGAGATGGAGTCACTGACTGCTAATATCGATTACATCAATGACAGTATT
	TCTGATTGTCAGGCCAACATAATCCAGATGGAAGAAGCAAAGGAAGAAGGTGAGACAT
	TGGATGTTACTGCAGTCATTAATGCCTGCACCCTTACAGAAGCCCGATACCTGCTAGA
	TCACTTCCTGTCAATGGGCATCAATAAGGGTCTTCAGGCTGCCCAGAAAOAGGGTCAA
	ATTAAAGTACTGGAAGGTCGACTCAAACAAACAGAAATAACCACTGCTACCCAAAACC
	AGCTCTTATTCCATATGTTGAAAGAGAAGGCAGAATTAAATCCTGAGCTAGATGCTTT
	ACTAGGCCATGCTTTACAAGATCTAGATAGCGTACCATTAGAAAATGTAGAGGATAGT
	ACTGATGAGGATGCTCCTTTAAACAGCCCAGGATCAGAAGGAAGCACGCTGTCTTCAG
	ATCTCATGAAGCTTTGTGGTGAAGTGAAACCTAAGAACAAGGCCCGAACCAGAACCAC
	CACTCAGATGGAATTGCTGTATGCAGATAGCAGTGAACTAGCTTCAGACACTAGTACA
	CGAGATGCCTCCTTGCCTGGCCCTCTCACACCTGTTGCAGAAGGGCAAGAGATTGGAA
	TGAATACACAGACAAGTGGTACTTCTGCTAGGGAAAAAGAGCTCTCTCCCCCACCTGG
	CTTACCTTCTAAGATAGGCAGCATTTCCAGGCAGTCATCTCTATCAGAAAAAAAAATT
	CCAGAGCCTTCTCCTGTAACAAGGAGAAAGGCATATGAGAAAGCAGAAAAATCAAAGG
	CCAAGGAACAAAAGCACTCAGATTCTGGAACTTCAGAGGCTAGTCTTTCACCTCCTTC
	TTCCCCACCAAGCCGGCCCCGTAATGAACTGAATGTTTTTAATCGTCTTACTGTTTCT
	CAGGGAAACACATCAGTTCAGCAGGATAAGTCTGATGAAAGTGACTCCTCTCTCTCGG
	AGGTACACAGATCCTCCAGAAGGGGCATAATCAACCCATTTCCTGCTTCAAAAGGAAT
	CAGAGCTTTTCCACTTCAGTGTATTCACATAGCTGAAGGGCATACAAAAGCTGTGCTC
	TGTGTGGATTCTACTGATGATCTCCTCTTCACTGGATCAAAAGATCGTACTTGTAAAG
	TATGGAATCTGGTGACTGGGCAGGAAATAATGTCACTGGGGGGTCATCCCAACAATGT
	CGTGTCTGTAAAATACTGTAATTATACCAGTTTGGTCTTCACTCTATCAACATCTTAT
	ATTAAGGTGTGGGATATCAGAGATTCAGCAAAGTGCATTCGAACACTAACGTCTTCAG
	GTCAAGTTACTCTTGCAGATGCTTGTTCTGCAAGTACCAGTCGAACAGTAGCTATTCC
	TTCTGGAGAGAACCAGATCAATCAAATTGCCCTAAACCCAACTGGCACCTTCCTCTAT
	GCTGCTTCTGGAAATGCTGTCAGGATGTGGGATCTTAAAAGGTTTCAGTCTACAGGAA
	AGTTAACAGGACACCTAGGCCCTGTTATGTGCCTTACTGTGGATCAGATTTCCAGTGG
	ACAAGATCTAATCATCACTGGCTCCAAGGATCATTACATCAAAATGTTTGATGTTACA
	GAAGGAGCTCTTGGGACTGTGAGTCCCACCCACAATTTTGAACCCCCTCATTATGATG
	GCATAGAAGCACTAACCATTCAAGGGGATAACCTATTTAGTGGGTCTAGAGATAATGG
	AATCAAGAAATGCGACTTAACTCAAAAAGACCTTCTTCAGCAAGTTCCAAATGCACAT
	AAGGATTGGGTCTGTGCCCTGGGAGTGGTGCCAGACCACCCAGTTTTGCTCAGTGGCT
	GCAGAGGGGGCATTTTGAAAGTCTGGAACATGGATACTTTTATGCCAGTGGGAGAGAT
	GAAGGGTCATGATAGTCCTATCAATGCCATATGTGTTAATTCCACCCACATTTTTACT
	GCAGCTGATGATCGAACTGTGAGAATTTGGAAGGCTCGCAATTTGCAAGATGGTCAGA
	TCTCTGACACAGGAGATCTGGGGGAAGATATTGCCAGTAATTAAACATGGAATGAAGAT
	AGGTTGTAAACTGAATGCTGTGATAATACTCTGTATTCTTTATGGAAAATGTTGTCCT
	GTACTTACTAGGCAAAACGTATGAATCGGATTAACTGGAAAATATATCTGAATTCAAC
	TGCTGACTATAAATGGTATTCTAATAAAATTGTGTACTATCCTGTGTGCTTAGTTTTA
	AGATCAACCAATAGATATATATCCTACAATTGATATATTGCTTTATTCACACTTTTAT
	TGTGGCTGAATTTTTGTGCCTATCTATAAAACACACTTTCAAATTATTTGAATTACC
	ORF Start: ATG at 163		ORF Stop: TAA at 5146
	SEQ IDNO:60	1661 aa	MW at 185479.3 Da
NOV14a,	MLGAPDESSVRVAVRXRPQLAKEKIEGCHICTSVTPGEPQVFLGKDKAFTFDYVFDID
CG113803-01	SQQEQIYTQCIEKLIEGCFEGYNATVFAYGQTGAGKTYTMGTGFDVNIVEEELGIISR
Protein Sequence	AVKHLFKSIEEKKHIAIKNGLPAPDFKVNAQFLELYNEEVLDLFDTTRDIDAKSKKSU
	IRIHEDSTGGIYTVGVTTRTVNTESEMMQCLKLGALSRTTASTQMNVQSSRSHATFTI
	HVCQTRVCPQIDADNATDNKIISESAQMNEFETLTAKFHFVDLAGSERLKRTGATGER
	AKEGISINCGLLALGNVISALGDKSKRATHVPYRDSKLTRLLQDSLGGNSQTIMIACV
	SPSDRDFMETLNTLKYANRARNIKNKVMVNQDRASQQINALRSEITRLQMELMEYKTG
	KRIIDEEGVESINDMFHENAMLQTENNNLRVRIKAMQETVDALRSRITQLVSDQANHV
	LARAGEGNEEISNMIHSYIKEIEDLRAKLLESEAVNENLRKNLTRATARAPYFSGSST
	FSPTILSSDKETIEIIDLAKKDLEKLKKKKKRKKKSVAGKEDNTDTDQEKKEEKGVSE
	RENNELEVEESQEVSDHEDEEEEEEEEEDDIDGGESSDESDSESDEKANYQADLANIT
	CEIAIKQKLIDELENSQKRLQTLKKQYEEKLMMLQHKIRDTQLERDQVLQNLGSVESY
	SEEKAKKVRSEYEKKLQAMNKELQRLQAAQKEHARLLKNQSQYEKQLKKLQQDVMEMK
	KTKVRLMKQMKEEQEKARLTESRRNREIAQLKKDQRKRDHQLRLLEAQKRNQEVVLRR
	KTEEVTALRRQVRPMSDKVAGKVTRKLSSSDAPAQDTGSSAAAVETDASRTGAQQKMR
	IPVARVQALPTPATNGNRKKYQRKGLTGRVFISKTARMKWQLLERRVTDIIMQKNTIS
	NEADMNRLLKQREELTKRREKLSKRREKIVKENGEGDKNVANINEEMESLTANIDYI
	NDSISDCQANIMQMEEAKEEGETLDVTAVINACTLTEARYLLDHFLSMGINKGLQAAQ
	KEAQIKVLEGRLKQTEITSATQNQLLFHMLKEKAELNPELDALLGHALQDLDSVPLEN
	VEDSTDEDAPLNSPGSEGSTLSSDLMKLCGEVKPKNKARRRTTTQMELLYADSSELAS
	DTSTGDASLPGPLTPVAEGQEIGMNTETSGTSAREKELSPPPGLPSKIGSISRQSSLS
	EKKIPEPSPVTRRKAYEKAEKSKAKEQKHSDSGTSEASLSPPSSPPSRPRNELNVFNR
	LTVSQGNTSVQQDKSDESDSSLSEVHRSSRRGIINPFPASKGIRAFPLQCIHIAEGHT
	KAVLCVDSTDDLLFTGSKDRTCKVWNLVTGQEIMSLGGHPNNVVSVKYCNYTSLVFTV
	STSYIKVWDIRDSAKCIRTLTSSGQVTLGDACSASTSRTVAIPSGENQTNQIALNPTG
	TFLYAASGNAVRMWDLKRFQSTGKLTGHLGPVMCLTVDQISSGQDLIITGSKDHYIKM
	FDVTEGALGTVSPTHNFEPPHYDGIEALTIQGDNLFSGSRDNGIKKWDLTQKDLLQQV
	PNAHKDWVCALGVVPDHPVLLSGCRGGILKVWNMDTFMPVGEMKGHDSPINAICVNST
	HIFTAADDRTVRIWKARNLQDCQISDTGDLGEDIASN

[0390] Further analysis of the NOV14a protein yielded the following properties shown in Table 14B.

TABLE 14B
Protein Sequence Properties NOV14a
PSort     0.9800 probability located in nucleus; 0.4276
analysis: probability located in mitochondrial matrix space; 0.3000
          probability located in microbody (peroxisome); 0.1057
          probability located in mitochondrial inner membrane
SignalP   No Known Signal Sequence Predicted
analysis:

[0391] A search of the NOV14a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 14C.

TABLE 14C
Geneseq Results for NOV14a
		NOV14a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB90728	Human CT797_3 protein sequence	753 . . . 1661	908/910 (99%)	0.0
	SEQ ID 153 - Homo sapiens, 910 aa.	1 . . . 910	908/910 (99%)
	[WO200119988-A1, 22-MAR-2001]
AAW69248	Clone CT797_protein sequence -	753 . . . 1661	908/910 (99%)	0.0
	Homo sapiens, 910 aa.	1 . . . 910	908/910 (99%)
	[WO9825962-A2, 18 JUN. 1998]
AAM78832	Human protein SEQ ID NO 1494 -	753 . . . 1638	486/896 (54%)	0.0
	Homo sapiens, 883 aa.	1 . . . 858	640/896 (71%)
	[WO200157190-A2, 09 AUG. 2001]
AAM79816	Human protein SEQ ID NO 3462 -	778 . . . 1638	469/871 (53%)	0.0
	Homo sapiens, 879 aa.	22 . . . 854	618/871 (70%)
	[WO200157190-A2, 09 AUG. 2001]
ABB61405	Drosophila melanogaster	7 . . . 1125	450/1149 (39%)	0.0
	polypeptide SEQ ID NO 11007 -	11 . . . 968	634/1149 (55%)
	Drosophila melanogaster, 1003 aa.
	[WO200171042-A2, 27 SEP. 2001]

[0392] In a BLAST search of public sequence datbases, the NOV14a protein was found to have homology to the proteins shown in the BLASTP data in Table 14D.

TABLE 14D
Public BLASTP Results for NOV14a
		NOV14a
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q9QXL2	Kif21a - Mus musculus (Mouse),	1 . . . 1522	1203/1588 (75%)	0.0
	1573 aa.	1 . . . 1563	1297/1588 (80%)
Q9QXL1	Kif21b - Mus musculus (Mouse),	10 . . . 1638	998/1646 (60%)	0.0
	1668 aa.	9 . . . 1614	1261/1646 (75%)
Q9C0F5	KIAA1708 protein - Homo	748 . . . 1661	914/914 (100%)	0.0
	sapiens (Human), 914 aa	1 . . . 914	914/914 (100%)
	(fragment).
Q9NXU4	CDNA FLJ20052 fis, clone	1 . . . 576	572/576 (99%)	0.0
	C0L00777 - Homo sapiens	1 . . . 576	576/576 (99%)
	(Human), 576 aa (fragment).
Q9Y590	NY-REN-62 antigen - Homo	1 . . . 582	549/583 (94%)	0.0
	sapiens (Human), 633 aa	49 . . . 631	556/583 (95%)
	(fragment).

[0393] PFam analysis predicts that the NOV14a protein contains the domains shown in the Table 14E.

TABLE 14E
Domain Analysis of NOV14a
		Identites/
Pfam	NOV14a	Similarites	Expect
Domain	Match Region	for the Matched Region	Value
kinesin	15 . . . 400	169/433 (39%)	7.6e−130
		292/433 (67%)
WD40	1326 . . . 1360	12/37 (32%)	7.2e−05
		31/37 (84%)
WD40	1431 . . . 1465	10/37 (27%)	0.23
		28/37 (76%)
WD40	1471 . . . 1510	12/40 (30%)	0.039
		31/40 (78%)
WD40	1563 . . . 1599	10/37 (27%)	0.003
		30/37 (81%)
WD40	1605 . . . 1639	10/37 (27%)	2.4e−05
		32/37 (86%)

Example 15

[0394] The NOV15 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 15A.

TABLE 15A
NOV15 Sequence Analysis
	SEQ ID NO:61	1006 bp
NOV15a,	CCGGGCATGAGTTAGTCGCAGACATGGACACCAAACATTTCCTGCCGCTCGATTTCTC
CG113833-01 DNA	CACCCAGGTGAACTCCTCCCTCACCTCCCCGACGGGGCCAGGCTCCATGGCTGCCCCC
Sequence	TCGCTGCACCCGTCCCTGGGGCCTGGCATCGCCTCCCGGCGACAGCTGCATTCTCCCA
	TCAGCACCCTGAGCTCCCCCATCAACGGCATGGGCCCGCCTTTCTCGGTCATCAGCTC
	CCCCATGGGCCCCCACTCCATGTCGGTGCCCACCACACCCACCCTGGCCTTCAGCACT
	GGCAGCCCCCAGCTCAGCTCACCTATGAACCCCAGCTCGCCGAACGACCCTCTCACCA
	ACATTTGCCAAGCAGCCGACAAACAGCTTTTCACCCTGGTGGAGTCGGCCAAGCGGAT
	CCCACACTTCTCAGAGCTGCCCCTGGACGACCAGGTCATCCTGCTGCGGGCAGGCTGG
	AATGAGCTGCTCATCGCCTCCTTCTCCCACCGCTCCATCGCCGTGAAGGACGGGATCC
	TCCTGGCCACCGGGCTGCACGTCCACCGGAACAGCGCCCACAGCGCAGGGGTGGGCGC
	CATCTTTGACAGGGTGCTGACGGAGCTTGTGTCCAAGATGCGGGACATGCAGATGGAC
	AAGACGGAGCTGGGCTGCCTGCGCGCCATCGTCCTCTTTAACCCTGACTCCAAGGGGC
	TCTCGAACCCGGCCGAGGTGGAGGCGCTGAGGGAGAAGGTCTATGCCTCCTTGGAGGC
	CTACTGCAAGCACAAGTACCCAGAGCAGCCGGGAAGGTTCGCTAAGCTCTTCCTCCGC
	CTGCCGGCTCTGCGCTCCATCGGGCTCAAATGCCTGGAACATCTCTTCTTCTTCAAGC
	TCATCGGGGACACACCCATTGACACCTTCCTTATGGAGATGCTGGAGGCGCCGCACCA
	AATGACTTAGGCCTGCGGGCAAATGACTTAGGCCTGCGGGCAAATGACTTAGGCCTGC
	GGGCAAATGACTTAGGCCTG
	ORF Start: ATG at 24		ORF Stop: TAG at 936
	SEQ ID NO:62	304 aa	MW at 32984.7 Da
NOV15a,	MDTKHFLPLDFSTQVNSSLTSPTGRGSMAAPSLHPSLGPGIGSPGQLHSPISTLSSPI
CG113833-01	NGMGPPFSVISSPMGPHSMSVPTTPTLGFSTGSPQLSSPMNPSSPNDPVTNICQAADK
Protein Sequence	QLFTLVEWAKRIPHFSELPLDDQVILLRAGWNELLIASFSHRSIAVKDCILLATCLHV
	HNSHSAGVGAIFDRVLTELVSKMRDMQMDKTELGCLRAIVLFNPDSKGLSNPAEVE
	ALREKVYASLEAYCKHKYPEQPGRFAKLLLRLPALRSIGLKCLEHLFFFKLIGDTPID
	TFLMEMLEAPHQMT

[0395] Further analysis of the NOV15a protein yielded the following properties shown in Table 15B.

TABLE 15B
Protein Sequence Properties NOV15a
PSort     0.4500 probability located in cytoplasm; 0.3535 probability
analysis: located in microbody (peroxisome); 0.1657 probability located
          in lysosome (lumen); 0.1000 probability located in
          mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0396] A search of the NOV15a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 15C.

TABLE 15C
Geneseq Results for NOV15a
		NOV15a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU7826	Human Retinoid X Receptor alpha	98 . . . 304	206/207 (99%)	e−117
	(RXRalpha) protein - Homo sapiens,	256 . . . 462	207/207 (99%)
	462 aa. [WO200218420-A2, 07 MAR. 2002]
AAM50627	Retinoic acid receptor-alpha - Homo	98 . . . 304	206/207 (99%)	e−117
	sapiens, 242 aa. [WO200197856-A2,	36 . . . 242	207/207 (99%)
	27 DEC. 2001]
ABB04293	Human retinoid receptor RXRalpha -	98 . . . 304	206/207 (99%)	e−117
	Homo sapiens, 462 aa.	256 . . . 462	207/207 (99%)
	[WO200185787-A2, 15 NOV. 2001]
AAU10272	Human RXR ligand binding domain	98 . . . 304	206/207 (99%)	e−117
	HsRXR-EF - Homo sapiens, 237 aa.	31 . . . 237	207/207 (99%)
	[WO200170816-A2, 27 SEP. 2001]
AAU10271	Human RXR ligand binding domain	98 . . . 304	206/207 (99%)	e−117
	HsRXR-DEF - Homo sapiens, 262	56 . . . 262	207/207 (99%)
	aa. [WO200170816-A2, 27 SEP. 2001]

[0397] In a BLAST search of public sequence datbases, the NOV15a protein was found to have homology to the proteins shown in the BLASTP data in Table 15D.

TABLE 15D
Public BLASTP Results for NOV15a
		NOV15a
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
AAG02188	Retinoic acid receptor RXR -	98 . . . 304	206/207 (99%)	e−116
	Cloning vector pFB-ERV, 472 aa.	266 . . . 472	207/207 (99%)
AAC95154	RETINOIC ACID RECEPTOR	98 . . . 304	206/207 (99%)	e−116
	RXR - Cloning vector pERV3,	273 . . . 479	207/207 (99%)
	479 aa.
P19793	Retinoic acid receptor RXR-alpha -	98 . . . 304	206/207 (99%)	e−116
	Homo sapiens (Human), 462 aa.	256 . . . 462	207/207 (99%)
AAB36777	RXR alpha 2 - Mus musculus	98 . . . 304	205/207 (99%)	e−116
	(Mouse), 439 aa.	233 . . . 439	206/207 (99%)
Q05343	Retinoic acid receptor RXR-alpha -	98 . . . 304	205/207 (99%)	e−116
	Rattus norvegicus (Rat), 467 aa.	261 . . . 467	206/207 (99%)

[0398] PFam analysis predicts that the NOV15a protein contains the domains shown in the Table 15E.

TABLE 15E
Domain Analysis of NOV15a
		Identities/
Pfam	NOV15a	Similarites	Expect
Domain	Match Region	for the Matched Region	Value
hormone_rec	115 . . . 297	79/207 (38%)	1.5e−71
		160/207 (77%)

Example 16

[0399] The NOV16 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 16A.

TABLE 16A
NOV16 Sequence Analysis
	SEQ ID NO:63	1057 bp
NOV16a,	CACACGCTGACTGAGATGTCGTCCACTGCGGCTTTTTACCTTCTCTCTACGCTACGAG
CG114150-01 DNA	GATACTTGGTGACCTCATTCTTGTTGCTTAAATACCCGACCTTGCTGCACCAGAGAAA
Sequence	GAAGCAGCGATTCCTCAGTAAACACATCTCTCACCGCGGAGGTGCTGGAGAAAAATTTG
	GAGAATACAATGGCAGCCTTTCAGAGTGCGGTTAAAATCGGAACTGATATGCTAGAAT
	TGGACTGCCATATCACAAAAGATGAACAAGTTGTAGTGTCACATGATGAGAATCTAAA
	CAGAGCAACTGGGGTCAATGTAAACATCTCTGATCTCAAATACTGTGAGCTCCCACCT
	TACCTTGGCAAACTGGATGTCTCATTTCAAAGAGCATGCCAGTGTGAAGGAAAAGATA
	ACCGAATTCCATTACTGAAGGAAGTTTTTGAGGCCTTTCCTAACACTCCCATTAACAT
	CGATATCAAAGTCAACAACAATGTGCTGATTAAGAAGGTATCAGAGTTGGTGAAGCGG
	TATAATCGAGAACACTTAACAGTGTGGGGTAATGCCAATTATGAAATTGTAGAAAAGT
	GCTACAAAGAGAATTCAGATATTCCTATACTCTTCAGTCTACAACGTGTCCTGCTCAT
	TCTTGGCCTTTTCTTCACTGGCCTCTTGCCCTTTGTGCCCATTCGAGAACAGTTTTTT
	GAAATCCCAATGCCTTCTATTATACTGAAATTGACTAAATTAGGACTAAGGACTAAAT
	TCCTAAATCAGTTTTGCTTTTTCTTTTCTAGCTTACTAATGAGGAAAGCTTTGTTTGA
	CCACCTAACTGCTCGAGGCATTCAGGTGTATATTTGGGTATTAAATGAAGAACAAGAA
	TACAAAAGAGCTTTTGATTTGGGAGCAACTGGGGTGATGACAGACTATCCAACAAAGC
	TTAGGGATTTTTTACATAACTTTTCAGCATAGAAAAAGAGGTACTTAGAAGTATTGAA
	GGAAAAAATGAAGACCTAAGAAAAAAATATTTCATGATCATTTCCCTAAGCCATTTCC
	AGAATGGTAAAAG
	ORF Start: ATG at 16		ORF Stop: TAG at 958
	SEQ ID NO:64	314 aa	MW at 36084.6 Da
NOV16a,	MSSTAAFYLLSTLGGYLVTSFLLLKYPTLLHQRKKQRFLSKHISHRGGAGENLENTMA
CG114150-01	AFQSAVKIGTDMLELDCHITKDEQVVVSHDENLKRATGVNVNISDLKYCELPPYLGKL
Protein Sequence	DVSFQRACEQCEGKDNRIPLLKEVFEAFPNTPINIDIKVNNNVLIKKVSELVKRYNREH
	LTVWGNANYEIVEKCYKENSDIPILFSLQRVLLILGLFFTGLLPFVPIREQFFEIPMP
	SIILKLTKLGLRTKFLNQFCFFFSSLLMRKALFDHLTARGIQVYILWVLNEEQEYKRAF
	DLGATGVMTDYPTKLRDFLHNFSA
	SEQ ID NO:65	501 bp
NOV16b,	GGATCCAGAAAGAAGCAGCGATTCCTCAGTAAACACATCTCTCACCGCGGAGGTGCTG
210982611 DNA	GAGAAAATTTGGAGAATACAATGGCAGCCTTTCAGCATGCGGTTAAAATCGGAACTGA
Sequence	TATGCTAGAATTGGACTGCCATATCACAAAAGATGAACAAGTTGTAGTGTCACATGAT
	GAGAATCTAAACAGAGCAACTGGGGTCAATGTAAACATCTCTGATCTCAAATACTGTG
	AGCTCCCACCTTACCTTGGCAAACTGGATGTCTCACTTCAAAGAGCATGCCAGTGTGA
	AGGAAAAGATAACCGAATTCCATTACTGAAGGAAGTTTTTGAGGCCTTTCCTAACACT
	CCCATTAACATCGATATCAAAGTCAACAACAATGTGCTGATTAAGAAGGTTTCAGAGT
	TGGTGAAGCGGTATAATCGACAACACTTAACAGTGTGGGGTAATGCCAATTATGAAAT
	TGTAGAAAAGTGCTACAAAGACAATTCAGATGTCGAC
	ORF Start: at 1		ORF Stop: end of sequence
	SEQ ID NO:66	1167 aa	MW at 19007.5 Da
NOV16b,	GSRKKQRFLSKHISHRCGAGENLENTMAAFQHAVKIGTDMLELDCHITKDEQVVVSHD
210982611 Protein	ENLKRATGVNVNISDLKYCELPPYLGKLDVSLQRACQCEGKDNRIPLLKEVFEAFPNT
Sequence	PINIDIKVNNNVLIKKVSELVKRYNREHLTVWGNANYEIVEKCYKENSDVD
	SEQ ID NO:67	510 bp
NOV16c,	GGATCCAGAAAGAAGCAGCGATTCCTCAGTAAACACATCTCTCACCGCGGAGGTGCTG
211546798 DNA	GAGAAAATTTGGAGAATGCAATGGCAGCCTTTCAGCATGCGGTTAAAATCGGAACTGA
Sequence	TATGCTAGAATTGGACTGCCATATCGCAAAAGATGAACAAGTTGTAGTGTCACATGAT
	GAGAATCTAAAGAGAGCAACTGGGGTCAATGTAAACATCTCTGATCTCAAATACTGTG
	AGCTCCCACCTTACCTTGGCAAACTGGATGTCTCATTTCAAAGAGCATGCCAGTGTGA
	AGGAAAAGATAACCGAATTCCATTACTGAAGGAAGTTTTTGAGGCCTTTCCTAAGACT
	CCCATTAACATCGATATCAAAGTCAACAACAATGTGCTGATTAAGAAGGTTTCAGAGT
	TGGTGAAGCGGTATAATCGAGAACACTTAACAGTGTGGGGTAATGCCAATTATGAAAT
	TGTAGAAAAGTGCTACAAAGAGAATTCAGATGTCGAC
	ORF Start: at 1		ORF Stop: end of sequence
	SEQ ID NO:68	167 aa	MW at 18981.4 Da
NOV16c,	GSRKKQRFLSKHISHRGGAGENLENAMAAFQHAVKIGTDMLELDCHIAKDEQVVVSHD
21546798 Protein	ENLKRATGVNVNISDLKYCELPPYLGKLDVSFQRACQCEGKDNRIPLLKEVFEAFPNT
Sequence	PINIDIKVNNNVLIKKVSELVKRYNREHLTVWGNANYEIVEKCYKENSDVD
	SEQ ID NO:69	501 bp
NOV16d,	GGATCCAGAAAGAAGCAGCGATTCCTCAGTAAACACATCTCTCACCGCGGAGCTGCTG
211546812 DNA	GAGAAAATTTGGAGAATACAATGGCAGCCTTTCAGCATGCGGTTAAAATCGGAACTGA
Sequence	TATGCTAGAATTGGACTGCCATATCACAAAAGATGTACAAGTTGTAGTGTCACATGAT
	GAGAATCTAAAGAGAGCAACTGGGGTCAATGTAAACATCTCTGATCTCAAATACTCTG
	AGCTCCCACCTTACCTTGGCAAACTGGATGTCTCATTTCAAAGAGCATGCCAGTGTGA
	AGGAAAAGATAACCCAATTCCATTACTGAAGGAAGTTTTTGAGGCCTTTCCTAACACT
	CCCATTAACATCGATATCAAAGTCAACAACAATGTGCTGATTAAGAAGGTTTCAGAGT
	TGGTGAAGCGGTATAATCGAGAACACTTAACAGTGTGGGGTAATGCCAATTATGAAAT
	TGTAGAAAAGTGCTACAAAGAGAATTCAGATGTCGAC
	ORF Start: at 1		ORF Stop: end of sequence
	SEQ ID NO:70	167 aa	MW at 19011.5 Da
NOV16d,	GSRKKQRFLSKHISHRGGAGENLENTMAAFQHAVKIGTDMLELDCHITKDVQVVVSHD
211546812 Protein	ENLKRATGVNVNISDLKYCELPPYLGKLDVSFQRACQCEGKDNRIPLLKEVFEAFPNT
Sequence	PINIDIKVNNNVLIKKVSELVKRYNREHLTVWGNANYEIVEKCYKENSDVD
	SEQ ID NO:71	501 bp
NOV16e,	GGATCCAGAAAGAAGCAGCGATTCCTCAGTAAACACATCTCTCACCGCGGAGGTGCTG
211546816 DNA	GAGAAAATTTGGAGAATACAATGGCAGCCTTTCAGCATGCGGTTAAAATCGGAACTGA
Sequence	TATGCTAGAATTGGACTGCCATATCACAAAAGATGAACAAGTTGTAGTGTCACATGAT
	GAGAATCTAAAGAGAGCAACTGGGGTCAATGTAAACATCTCTGATCTCAAATACTGTG
	AGCTCCCACCTTACCTTGGCAAACTGGATGTCTCATTTCAAAGAGCATGCCAGTGTGA
	AGGAAAAGATAACCGAATTCCATTACTGAAGGAGGTTTTTGAGGCCTTTCCTAACACT
	CCCATTAACATCGATATCAAAGTCAACAACAATGTGCTGATTAAGAAGGTTTCAGAGT
	TGGTGAAGCCGTATAATCGAGAACACTTAACAGTGTGGGGTAATGCCAATTATGAAAT
	TGTAGAAAAGTGCTACAAAGAGAATTCAGATGTCGAC
	ORF Start: at 1		ORF Stop: end of sequence
	SEQ ID NO:72	167 aa	MW at 19051.5 Da
NOV16e,	GSRKKQRFLSKHISHRGGAGENLENTMAAFQHAVKIGTDMLELDCHITKDEQVVVSHD
211546816 Protein	ENLKRATGVNVNISDLKYCELPPYLGKLDVSFQRACQCEGKDNRIPLLKEVFEAFPNT
Sequence	PINIDIKVNNNVLIKKVSELVKRYNREHLTVWGNANYEIVEKCYKENSDVD
	SEQ ID NO:73	501 bp
NOV16f,	GGATCCAGAAAGAAGCAGCGATTCCTCAGTAAACACATCTCTCACCGCGGAGGTGCTG
21154682 DNA	GAGAAAATTTGGAGAATACAATGGCAGCTTTTCAGCATGCGGTTAAAATCGGAACTGA
Sequence	TATGCTAGAATTGGACTGCCATATCACAAAGGATGAACAAGTTGTAGTGTCACATGAT
	GAGAATCTAAAGAGAGCAACTGGGGTCAATGTAAACATCTCTGATCTCAAATACTGTG
	AGCTCCCACCTTACCTTGGCAAACTGGATGTCTCATTTCAAAGAGCATGCCAGTGTGA
	AGGAAAGATAACCGAATTCCATTACTGAAGGAAGTTTTTGAGGCCTTTCCTAACACT
	CCCATTAACATCGATATCAAAGTCAACAACAATGTGCTCATTAAGAAGGTTTCAGAGT
	TGGTGAAGCGGTATAATCGACAACACTTAACAGTGTGGGGTAATGCCAATTATGAAAT
	TGTAGAAAAGTGCTACAAAGAGAATTCAGATGTCGAC
	ORF Start: at 1		ORF Stop: end of sequence
	SEQ ID NO:74	167 aa	MW at 19041.5 Da
NOV16f,	GSRKKQRFLSKHISHRGGAGENLENTMAAFQHAVKIGTDMLELDCHITKDEQVVVSHD
211546824 Protein	ENLKRATGVNVNTSDLKYCELPPYLGKLDVSFQRACQCEGKDNRIPLLKEVFEAFPNT
Sequence	PINIDTKVNNNVLIKKVSELVKRYNREHLTVWGNANYEIVEKCYKENSDVD

[0400] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 16B.

TABLE 16B
Comparison of NOV16a against NOV16b through NOV16f.
Protein	NOV16a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV16b	33 . . . 196	161/164 (98%)
	3 . . . 166	162/164 (98%)
NOV16c	33 . . . 196	160/164 (97%)
	3 . . . 166	161/164 (97%)
NOV16d	33 . . . 196	161/164 (98%)
	3 . . . 166	162/164 (98%)
NOV16e	33 . . . 196	162/164 (98%)
	3 . . . 166	163/164 (98%)
NOV16f	33 . . . 196	162/164 (98%)
	3 . . . 166	163/164 (98%)

[0401] Further analysis of the NOV16a protein yielded the following properties shown in Table 16C.

TABLE 16C
Protein Sequence Properties NOV16a
PSort     0.7300 probability located in plasma membrane; 0.6400
analysis: probability located in endoplasmic reticulum (membrane);
          0.1486 probability located in microbody (peroxisome);
          0.1000 probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 33 and 34
analysis:

[0402] A search of the NOV16a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 16D.

TABLE 16D
Geneseq Results for NOV16a
		NOV16a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM49156	Human Myb protein 32 - Homo	1 . . . 268	246/268 (91%)	e−138
	sapiens, 289 aa. [CN1325886-A,	1 . . . 268	251/268 (92%)
	12 DEC. 2001]
ABB09007	Human phosphodiesterase−3 - Homo	1 . . . 192	191/192 (99%)	e−108
	sapiens, 210 aa. [WO200198471-	1 . . . 192	191/192 (99%)
	A2, 27 DEC. 2001]
AAE05493	Human phosphodiesterase−3	3 . . . 311	131/310 (42%)	1e−68
	(HPDE-3) - Homo sapiens, 318 aa.	2 . . . 310	197/310 (63%)
	[WO200155358-A2, 02 AUG. 2001]
AAU27639	Human protein AFP471025 - Homo	3 . . . 303	127/302 (42%)	2e−66
	sapiens, 330 aa. [WO200166748-	2 . . . 302	191/302 (63%)
	A2, 13 SEP. 2001]
AAM41071	Human polypeptide SEQ ID NO	68 . . . 311	106/245 (43%)	2e−53
	6002 - Homo sapiens, 300 aa.	50 . . . 292	158/245 (64%)
	[WO200153312-A1, 26 JUL. 2001]

[0403] In a BLAST search of public sequence datbases, the NOV16a protein was found to have homology to the proteins shown in the BLASTP data in Table 16E.

TABLE 16E
Public BLASTP Results for NOV16a
		NOV16a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9CRY7	2610020H15Rik protein (RIKEN	1 . . . 314	275/314 (87%)	e−156
	cDNA 26100201115 gene) - Mus	1 . . . 314	288/314 (91%)
	musculus (Mouse), 314 aa
	(fragment).
Q9D4X7	2610020H15Rik protein - Mus	1 . . . 314	274/314 (87%)	e−155
	musculus (Mouse), 314 aa.	1 . . . 314	287/314 (91%)
Q9CT14	2610020H15Rik protein - Mus	51 . . . 314	223/264 (84%)	e−125
	musculus (Mouse), 341 aa	78 . . . 341	236/264 (88%)
	(fragment).
CAC88621	Sequence 51 from Patent	3 . . . 303	127/302 (42%)	6e−66
	WO0166748 - Homo sapiens	2 . . . 302	191/302 (63%)
	(Human), 330 aa.
Q9D1C0	1110015E22Rik protein - Mus	7 . . . 309	125/304 (41%)	6e−65
	musculus (Mouse), 330 aa.	6 . . . 308	192/304 (63%)

[0404] PFam analysis predicts that the NOV16a protein contains the domains shown in the Table 16F.

TABLE 16F
Domain Analysis of NOV16a
		Identities/
		Similarities
	NOV16a	for the
Pfam Domain	Match Region	Matched Region	Expect Value
GDPD	45 . . . 306	62/283 (22%)	5.8e−18
		176/283 (62%)

Example 17

[0405] The NOV17 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 17A.

TABLE 17A
NOV17 Sequence Analysis
	SEQ ID NO:75	1710 bp
NOV17a,	GTCACTGAGACCCATGGCAACGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTT
CG114555-01 DNA	CCCCTCACAGATCACACCAGCCACGCCGGGCCTCCAGGGCCAGGGACGGCACTGCTGG
Sequence	AGTGTGACCACCTGAGGAGTGGGGTGCCAGGTGGAAGGAGAAGAAAGTACATCAAGGC
	CTTTTACAATGAGTCATGGGAAAGAAGGCATGGACGTCCAATAGACCCAGACACTCTG
	ACTCTGCTCTGGTCTGTGACTGTGTCCATATTCGCCATCGGTGGACTTGTGCGGACAT
	TAATTGTGAAGATGATTGGAAAGGTTCTTGGGAGGAAGCACACTTTGCTGGCCAATAA
	TGGGTTTGCAATTTCTGCTGCATTGCTGATGGCCTGCTCGCTGCAGGCAGGAGCCTTT
	GAAATGCTCATCGTGCGACGCTTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTG
	TGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGATCCGTGGCTCTCTGGGGCA
	GGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCTGCCC
	GAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTG
	CCGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTT
	GGAGAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCA
	GACGTTTCCCAAGAGGTAGAGGAGGTCGTGGCTGAGAGCCGCGTGCAGAGGAGCATCC
	GCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCAC
	CGTGATTGTCACCATGGCCTCCTACCAGCTCTGTGGCCTCAATGCAATTTGCTTCTAT
	ACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCT
	TGACTACAGGGCCCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCA
	CCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTCGG
	ACCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTA
	TCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTT
	CATCTTGACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCA
	GGCACCGTCAACTGGCTCTCCAACTTTGCTGTTGGCCTCCTCTTCCCATTCATTCAGA
	AAAGTCTCGACACCTACTGTTTCCTAGTCTTTGCTACAATTTGTATCACAGGTCCTAT
	CTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATCCAGAAATCAGCCAG
	GCATTTTCCAAAAGGAACAAAGCATACCCACCACAAGAGAAAATCGACTCAGCTGTCA
	CTGATGGTAACATAAATGGTGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAATTA
	TGTCAAAAACAGGATTGTCTACATGGATGATCTCACTTTTCAGGAAACTTAAAATTTA
	CCCATTATTGGGAAGCTTAAATGAATTGAAGCTATGCAAGTCTTTTATATTATTAAAT
	ATTTAAAAGTAAACCTGTACTAATCTAA
	ORF Start: ATG at 14		ORF Stop: TAA at 1535
	SEQ ID NO:76	1507 aa	MW at 55327.3 Da
NOV17a,	MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRKYIKAFYNE
CG114555-01 DNA	SWERRHGRPIDPDTLTLLWSVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAI
Protein Sequence	SAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAI
	FICIGVFTGQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLPDSPRYLLLEKHN
	EARAVKAFQTFLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVT
	MACYQLCGLNAIWFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRR
	PLLIGGFGLMGLFFGTLTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTG
	EFFQQSQRPAAFIIAGTVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYF
	VLPETKNRTYAEISQAFSKRNKAYPPEEKIDSAVTDGKINGRP
	SEQ ID NO:77	1757 bp
NOV17b,	GTCACTGAGACCCATGGCAAGGAAGCAAAATAGGAATTCCAAGGAACTGGGCCTAGTT
CG114555-03 DNA	CCCCTCACAGATGACACCAGCCACGCCGGGCCTCCAGGGCCAGGGAGGGCACTGCTGG
Sequence	AGTGTGACCACCTGAGGAGTGGGGTGCCAGGTGGAAGGAGAACAAAGCAGCCTCTACG
	GAGCACCTCCTCTGCAGCAGGCTCCTCAACAACATATGTGGCCAGTCCTGCTATTAAG
	ATCCCATTTCACAGGTGGGCAAGCTTAGCCCCAGAAAAGTCAAGTCACTTGCTCAGAC
	TCCTACAGCTGAGGGGACTGGCCCTGGAGGTAAAGCTGATATCACTTGGCTCAAAGCC
	CCAAAGCTCTATCTCGTGGCTGGTGGCACTAGAGGAGACAAACGAGATTGGCAGAGAC
	TGGTCCTGCTCGCTCCTCGTGGCCTCCCTCGCGGGCGCCTTCCGCTCCTCCTTCCTCT
	ACGGCTACAACCTGTCGGTGGTGAATGCCCCCACCCCGCACACTTTGCTGGCCAATAA
	TGGGTTTGCAATTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTT
	GAAATGCTCATCGTGGGACGCTTCATCATGGGCATACATGGAGGCGTCGCCCTCAGTG
	TGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGATCCGTGGCTCTCTGGGGCA
	GGTGAGTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCTGCCC
	GAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTG
	CCGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCTGCACAGCCCACGCTACCTGCTCTT
	GGAGAAGCACAACGAGGCAAGAGCTGTGAAACCCTTCCAACGTTCTTGGGTAAAGCA
	GACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGACAGCCGCGTGCAGAGCAGCATCC
	GCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCAC
	CGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATCCAATTTGGTTCTAT
	ACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCT
	TGAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCA
	CCTGGGACGGAGACCCCTCCTCATTGGTGCCTTTGGGCTCATGCGCCTCTTCTTTGGG
	GCCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTA
	TCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTT
	CATCTTGACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCA
	GGCACCGTCAACTGGCTCTCCAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGA
	AAAGTCTGGACACCTACTCTTTCCTAGTCTTTGCTACAATTTGTATCACAGGTGCTAT
	CTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAAATCAGCCAG
	GCATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCTGTCA
	CTGATGGTAAGATAAATGGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAATTA
	TGTCAAAAACAGGATTG
	ORF Start: ATG at 14		ORF Stop: TAA at 1709
	SEQ ID NO:78	565 aa	MW at 6112.6 Da
NOV17b,	MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRKQPLRSTSS
CG114555-03	AAGSSTTYVASAAIKIPFHRWASLAPEKSSHLLRLLQLRGLALEVKLISLGSKPQSSI
Protein Sequence	SWLVALEETNEICRDWSCSLLVASLAGAFGSSFLYGYNLSVVNAPTPHTHLLANNGFAI
	SAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAI
	FICIGVFTGQLLGLPELLCKESTWPYLFCVIVVPAVVQLLSLPFLLDSPRYLLLEKHN
	EARAVKAFQTFLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVT
	MACYQLCGLNAIWFYTNSIFGKAGIPLAKIPYVTLSTCGIETLAAVFSGLVIEHLCRR
	PLLIGGFGLMGLFFGALTTTLTLQDHAPWVPYLSIVGILAIIASFCSGPCGIPFILTG
	EFFQQSQRPAAFIIAGTVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYF
	VLPETKNRTYAEISQAFSKRNKAYPPEEKIDSAVTDGKINGRP
	SEQ ID NO:79	1502 bp
NOV17c,	GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTT
CG114555-04 DNA	CCCCTCACAGATGACACCAGCCACGCCAGGCCTCCAGGGCCAGGGAGGGCACTGCTGG
Sequence	AGTGTGTCCACCTGAGGAGTGGGGTGCCAGCTGGAAGGAGAAGAAAGGACTGGTCCTG
	CTCGCTCCTCGTGGCCTCCCTCGCGGGCGCCTTCGGCTCCCCCTTCCTCTACGGCTAC
	AACCTGTCGGTGGTCAATGCCCCCACCCCGTACATCAAGGCCTTTTACAATCAGTCAT
	CGGAAAGAAGGCATGGACGTCCAATAGACCCAGACACTCTGACTCTGCTCTGGTCTGT
	GACTGTGTCCATATTCGCCATCGGTGGACTTGTGGGGACATTAATTGTGAAGATGATT
	GGAAAGGTTCTTGGGAAGGAGCACACTTTGCTGGCCAATAATGGGTTTGCAATTTCTG
	CTGCATTGCTGATGGCCTCCTCGCTGCAGCCAGGAGCCTTTGAGATGCTCATCGTGGG
	ACGCTTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGTCCTCCCCATGTACCTC
	AGTGAGATCTCACCCAAGGAGATCCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTA
	TCTGCATTGGCGTGTTCACTGGGCACCTTCTGGCCCTGCCCGAGCTGCTGGGAAAGGA
	GAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGCCGTTGTCCAGCTGCTG
	AGCCTTCCCTTTCTCCTGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACGAGG
	CAAGAGCTGTGAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGT
	AGAGGAGGTCCTCGCTGAGAGCCGCGTGCAGAGGAGCATCCGCCTCGTGTCCGTCCTG
	GAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACCGTGATTGTCACCATGG
	CCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATACCAACAGCATCTTTCG
	AAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCTTGAGTACAGGGGGCATC
	GAGACTTTGGCTGCCGTCTTCTCTGGCATCCCGTTCATCTTGACTGGTGAGTTCTTCC
	AGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTCCAA
	CTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTC
	CTAGTCTTTGCTACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTG
	AGACCAAAAACAGAACCTATGCAGAAATCAGCCAGGCATTTTCCAAAAGGAACAAAGC
	ATACCCACCAGAACAGAAAATCGACTCAGCTGTCACTGATGGTAAGATAAATGGAAGG
	CCTTAACAAGTTTCCTCCTCCACGTTGGACAATTATGTCAAAAACAGGATTG
	ORF Start: ATG at 14		ORF Stop: TAA at 1454
	SEQ ID NO:80	480 aa	MW at 52522.9 Da
NOV17c,	MARKQNRNSKELGLVPLTDDTSHARPPGPGRALLECVHLRSGVPGGRRRKDWSCSLLV
CG114555-04	ASLAGAFCSPFLYCYNLSVVNAPTPYIKAFYNESWERRHGRPIDPDTLTLLWSVTVSI
Protein Sequence	FAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAISAALLMACSLQAGAGEMLIVGRFIM
	GIDGGVALSVLPMYLSEISPKEIRCSLGQVTAIFICIGVFTGQLLGLPELLGKESTWP
	YLFGVIVVPAVVQLLSLPFLLDSPRYLLLEKHNEARAVKAFQTFLGKADVSQEVEEVL
	AESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAIWFYTNSIFGKAGI
	PLAKIPYVTLSTGGIETLAAVFSGIPFILTGEFFQQSQRPAAFIIAGTVNWLSNFAVG
	LLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFSKRNKAYPPE
	EKIDSAVTDGKINGRP
	SEQ ID NO:81	1087 bp
NOV17d,	AGGCTCCGCGGCCGCCCCCTTCACCGGTACCAGGAAGCACACTTTGCTGGCCAATAAT
247847070 DNA	GGCTTTGCAATTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTG
Sequence	AAATGCTCATCGTGGGACGTTTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGT
	GCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGATCCGTGGCTCTCTGGGGCAG
	GTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCTGCCCG
	AGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTCTGGTCCCTGC
	CGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTG
	GAGAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAC
	ACATTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAGCCGCGTGCAGAGGAGCATCCG
	CCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACC
	GTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATA
	CCAACAGCATCTTTGGAAAAGCTGGGATCCCTCCGGCAAAGATCCCATACGTCACCTT
	GAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGACCACGCCCCCTGGGTC
	CCCTACCTGAGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAG
	GTGGCATCCCGTTCATCTTGACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGC
	CTTCATCATTGCAGGCACCGTCAACTGGCTCTCCAACTTTGCTGTTGGGCTCCTCTTC
	CCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAATTTCTA
	TCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGC
	AGAAATCAGCCAGGCATTTCTCGAGGGCAAGGGTGGGCGCGCC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO:82	1362 aa	MW at 39164.5 Da
NOV17d,	GSAAAPFTGTRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSV
247847070 Protein	LPMYLSEISPKEIRGSLGQVTAIFILCIGVFTGQLLGLPELLGKESTWPYLFGVIVVPA
Sequence	VVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQTFLGKADISQEVEEVLAESRVQRSIR
	LVSVLELLRAPYVRWQWTVIVTMACYQLCGLNAIWFYTNSIFGKAGIPPAKIPYVTL
	STGGIETLAAVFSDHAPWVPYLSIVGILAIIASFCSGPGGILPFILTGEFFQQSQRPAA
	FIIAGTVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYA
	EISQAFLEOKGGRA
	SEQ ID NO:83	1189 bp
NOV17e,	AGGCTCCGCGGCCGCCCCCTTCACCGGTACCAGGAAGCACACTTTGCTGGCCAATAAT
247847059 DNA	GGGTTTGCAATTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCACGCAGGAGCCTTTG
Sequence	AAATGCTCATCGTGGGACGCTTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGT
	GCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGATCCGTGGCTCTCTGGGGCAG
	GTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCTGCCCG
	AGCTGCTGGGAAAGCAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGC
	CGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTG
	GAGAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAG
	ACATTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAGCCGCGTGCAGAGGAGCATCCG
	CCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACC
	GTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATA
	CCAACAGCATCTTTGGAAAAGCTGGGATCCCTCCGGCAAAGATCCCATACGTCACCTT
	GAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCAC
	CTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTGGGA
	CCCTCACCATCACGCTGACCCTGCAGCACCACGCCCCCTGGGTCCCCTACCTGAGTAT
	CGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTC
	ATCTTGACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAG
	GCACCGTCAACTGGCTCTCCAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAA
	AAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAATTTGTATCACAGGTGCTATC
	TACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAAATCAGCCAGG
	CATTTCTCGAGGGCAAGGGTGGGCGCGCC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO:84	396 aa	MW at 42801.9 Da
NOV17e,	GSAAAPFTGTRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSV
247847059 Protein	LPMYLSEISPKEIRGSLGQVTAIFTCIGVFTGQLLGLPELLGKESTWPYLFGVIVVPA
Sequence	VVQLLSLPFLPDSPRYLLLEKHNEAPAVKAFQTFLGKADISQEVEEVLAESRVQRSIR
	LVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAIWFYTNSIFGKAGIPPAKIPYVTL
	STGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFFGTLTITLTLQDHAPWVPYLSI
	VGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVNWLSNFAVGLLFPFIQK
	SLDTYCFLVFATICITGAIYLYFXTLPETKNRTYAEISQAFLEGKGGRA
	SEQ ID NO:85	1189 bp
NOV17f,	AGGCTCCGCGGCCGCCCCCTTCACCGGTACCAGGAAGCACACTTTGCTGGCCAATAAT
247847055 DNA	GGGTTTGCAATTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTG
Sequence	AAATGCTCATCGTGGGACGCTTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGT
	GCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGATCCGTGGCTCTCTGGGGCAG
	GTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTCGGCCTGCCCG
	AGCTGCTCCGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGC
	CGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGCACAGCCCACGCTACCTGCTCTTG
	GAGAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGCTAAAGCAG
	ACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAGCCACGTGCAGAGGAGCATCCG
	CCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACC
	GTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATA
	CCAACAGCATCTTTGGAAAAGCTGGGATCCCTCCGGCAAAGATCCCATACGTCACCTT
	GAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCAC
	CTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTGGGA
	CCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTAT
	CGTGGGCATTCTGGCCATCATCGCCTCTTTCTCCAGTGGGCCAGGTGGCATCCCGTTC
	ATCTTGACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAG
	GCACCGTCAACTGGCTCTCCAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAA
	AAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAATTTGTATCACAGGTGCTATC
	TACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAAATCAGCCAGG
	CATTTCTCGAGGGCAAGGGTGGGCGCGCC
	ORF Staff: at 2		ORF Stop: end of sequence
	SEQ ID NO:86	396 aa	MW at 42768.9 Da
NOV17f,	GSAAAPFTGTRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSV
247847055 Protein	LPMYLSEISPKEIRGSLGQVTAIFICILGVFTGQLLGLPELLGKESTWPYLFGVIVVPA
Sequence	VVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQTFLGKADVSQEVEEVLAESHVQRSIR
	LVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAILWFYTNSIFGKAGIPPAKIPYVTL
	STGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFFGTLTITLTLQDHAPWVPYLSI
	VGILAIIASFCSGPGGIPFILTCEFFQQSQRPAAFIIAGTVNWLSNFAVGLLFPFIQK
	SLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFLEGKGGRA
	SEQ ID NO:87	1189 bp
NOV17g,	AGGCTCCGCGGCCGCCCCCTTCACCGGTACCAGGAACCACACTTTGCTGGCCAATAAT
247847047	GGGTTTGCAATTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTG
Sequenece	AAATCCTCATCGTGGGACGCTTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGT
	GCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGATCCGTGGCTCTCTGGGGCAG
	GTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCTGCCCG
	AGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGC
	CGTTCTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTG
	GAGAAGCACAACGACGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAG
	ACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAGCCGCGTGCAGAGGAGCATCCG
	CCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACC
	GTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATA
	CCAACAGCATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCTT
	GAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATTCAGCAC
	CTGGCACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTGGGA
	CCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTAT
	CGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTC
	ATCTTGACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAG
	GCACCGTCAACTGGCTCTCCAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAA
	AAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAATTTGTATCACAGGTGCTATC
	TACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAAATCAGCCAGG
	CATTTCTCGAGGGCAAGGGTGGGCGCGCC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO:88	1396 aa	MW at 42803.9 Da
NOV17g.	GSAAAPFTGTRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSV
247847078 DNA	LPMYLSEISPKEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIVVPA
Sequence	VVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQTFLGKADVSQEVEEVLAESRVQRSIR
	LVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAIWFYTNSIFGKAGIPLAKIPYVTL
	STGGIETLAAVFSGLVILEHLGRRPLLIGGFGLMGLFFGTLTITLTLQDHAPWVPYLSI
	VGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVNWLSNFAVGLLFPFIQK
	SLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFLEGKGGRA
	SEQ ID NO:89	1267 bp
NOV17h,	AGGCTCCGCGGCCGCCCCCTTCACCGGTACCAGGAAGCACACTTTGCTGGCCAATAAT
247847078 DNA	GGGTTTGCAATTTCTGCTGCATTGCTGATCGCCTGCTCGCTCCAGGCAGGAGCCTTTG
Sequence	AAAATGCTCATCGTGGGACGCTTCATCATGGGCATAGATGGAGCCGTCGCCCTCAGTGT
	GCTCCCCATGTACCTCAGTGAGATCTCACCCAAGCAGATCCGTGGCTCTCTGGCGCAG
	GTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGCGCAGCTTCTGGGCCTGCCCG
	AGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTCATTGTGGTCCCTGC
	CGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTCCTCTTG
	GAGAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAG
	ACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAGCCACGTGCAGAGGAGCATCCG
	CCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACC
	GTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATA
	CCAACAGCATCTTTGGAAAAGCTGGGATCCCTCCGGCAAAGATCCCATACCCCACCTT
	GAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCAC
	CTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTCGGA
	CCCTCACCATCACGCGGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTAT
	CGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTC
	ATCTTGACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAG
	GCACCGTCAACTGGCTCTCCAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAA
	AAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAATTTGTATCACAGCTGCTATC
	TACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAAATCAGCCAGG
	CATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCTGTCAC
	TGATGGTAAGATAAATGGAAGGCCTCTCGAGGGCAAGGGTGGGCGCGCC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO:90	422 aa	MW at 45637.0 Da
NOV17h,	GSAAAPFTGTRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSV
247847078 Protein	LPMYLSEISPKEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIVVPA
Sequence	VVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQTFLGKADVSQEVEEVLAESHVQRSIR
	LVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAIWFYTNSIFGKAGIPPAKIPYATL
	STGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFFGTLTITRTLQDHAPWVPYLSI
	VGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVNWLSNFAVGLLFPFIQK
	SLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFSKRNKAYPPEEKIDSAVT
	DGKINGRPLEGKGGRA

[0406] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 17B.

TABLE 17B
Comparison of NOV17a against NOV17b through NOV17h.
	NOV17a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV17b	77 . . . 507	391/436 (89%)
	132 . . . 565	398/436 (90%)
NOV17c	1 . . . 507	439/540 (81%)
	1 . . . 480	440/540 (81%)
NOV17d	104 . . . 481	342/378 (90%)
	11 . . . 354	343/378 (90%)
NOV17e	104 . . . 481	354/378 (93%)
	11 . . . 388	355/378 (93%)
NOV17f	104 . . . 481	354/378 (93%)
	11 . . . 388	354/378 (93%)
NOV17g	104 . . . 481	356/378 (94%)
	11 . . . 388	356/378 (94%)
NOV17h	104 . . . 507	381/404 (94%)
	11 . . . 414	381/404 (94%)

[0407] Further analysis of the NOV17a protein yielded the following properties shown in Table 17C.

TABLE 17C
Protein Sequence Properties NOV17a
PSort     0.6000 probability located in plasma membrane; 0.4000
analysis: probability located in Golgi body; 0.3000 probability
          located in endoplasmic reticulum (membrane); 0.0300
          probability located in mitochondrial inner membrane
SignalP   No Known Signal Sequence Predicted
analysis:

[0408] A search of the NOV17a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 17D.

TABLE 17D
Geneseq Results for NOV17a
		NOV17a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Number	[Patent #, Date]	Residues	Portion	Value
AAM79422	Human protein SEQ ID NO 3068 -	1 . . . 507	506/540 (93%)	0.0
	Homo sapiens, 558 aa.	19 . . . 558	506/540 (93%)
	[WO200157190-A2, 09 AUG. 2001]
ABB11910	Human GLUT9 homologue, SEQ ID	1 . . . 507	506/540 (93%)	0.0
	NO: 2280 - Homo sapiens, 558 aa.	19 . . . 558	506/540 (93%)
	[WO200157188-A2, 09 AUG. 2001]
AAM41316	Human polypeptide SEQ ID NO	1 . . . 507	505/540 (93%)	0.0
	6247 - Homo sapiens, 558 aa.	19 . . . 558	505/540 (93%)
	[WO200153312-A1, 26 JUL. 2001]
AAE16788	Human transporter and ion channel-	1 . . . 504	500/537 (93%)	0.0
	25 (TRICH-25 protein - Homo	1 . . . 537	501/537 (93%)
	sapiens, 537 aa. [WO200192304-A2,
	06 DEC. 2001]
AAE14611	Human glucose transporter protein	1 . . . 500	498/533 (93%)	0.0
	GLUTX - Homo sapiens, 563 aa.	1 . . . 533	498/533 (93%)
	[U.S. Pat. No. 6346374-B1, 12 FEB. 2002]

[0409] In a BLAST search of public sequence datbases, the NOV17a protein was found to have homology to the proteins shown in the BLASTP data in Table 17E.

TABLE 17E
Public BLASTP Results for NOV17a
		NOV17a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9NRM0	Solute carrier family 2, facilitated	1 . . . 507	506/540 (93%)	0.0
	glucose transporter, member 9	1 . . . 540	506/540 (93%)
	(Glucose transporter type 9) -
	Homo sapiens (Human), 540 aa.
Q8WV30	Similar to solute carrier family 2	51 . . . 507	457/457 (100%)	0.0
	(facilitated glucose transporter),	55 . . . 511	457/457 (100%)
	member 9 - Homo sapiens (Human),
	511 aa.
P22732	Solute carrier family 2, facilitated	52 . . . 494	202/446 (45%)	e−112
	glucose transporter, member 5	46 . . . 491	291/446 (64%)
	(Glucose transporter type 5, small
	intestine) (Fructose transporter) -
	Homo sapiens (Human), 501 aa.
G02864	fructose transporter - human, 481 aa.	52 . . . 494	201/446 (45%)	e−111
		26 . . . 471	290/446 (64%)
Q8R1N7	Similar to solute carrier family 2	50 . . . 493	201/447 (44%)	e−111
	(facilitated glucose transporter),	43 . . . 489	290/447 (63%)
	member 5 - Mus musculus (Mouse),
	501 aa.

[0410] PFam analysis predicts that the NOV17a protein contains the domains shown in the Table 17F.

TABLE 17F
Domain Analysis of NOV17a
		Identities/
		Similarities
	NOV17a	for the
Pfam Domain	Match Region	Matched Region	Expect Value
sugar_tr	33 . . . 481	150/489 (31%)	1.1e−95
		335/489 (62%)

Example 18

[0411] The NOV18 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 18A.

TABLE 18A
NOV18 Sequence Analysis
	SEQ ID NO:91	534 bp
NOV18a,	AACTATGCTTTGTGATGTTCTGGGGAAAGGCTTTCGACTTCTTGGCTATGCTATTCAG
CG114784-01 DNA	TATGCCTATATTCTATATTGTGCTTTTGAATACATTGGTGGTGTTGTTATGTGTTCTG
Sequence	GACCACCAACGGAGCCTACCATTCAAAATTCAGATACTGTCTTTGCAGAAAATCTTGG
	TGTACATTTGTACGGTATTCAAAGAGGTGACATTGTGATTGCAAAAAGCCGAAGTGAT
	CCAAAATCAAATATTTGTAAAAAAGTAATTGGATTGGAAGGAGACAAAATCCTCGCCA
	CTAGTCCATCAGATTTCTTTAAAAGCCGTAGTTATGTGCCAGTGGGTCATGTTTGGTT
	AGAAGGTGATAATCTACAGAATTCTACAGATTCCAGGTACTATGGACCTATTCCATAT
	CGACTAATAAGAGGACGAATCTTCTTTAAGATTTGGCCTCTGAGTGATTTTGAGTTTT
	TACGTGCCAGCTCTAATGGCCACAGATTTTCTGATCATTGGTAAGCATTTATTCTTTT
	GACTTGATTATT
	ORF Start: ATG at 5		ORF Stop: TAA at 506
	SEQ ID NO:92	167 aa	MW at 18760.2 Da
NOV18a,	MLCDVLGKGFRLVGYAIQYGYILYCAFEYIGGVVMCSGPPTEPTIQNSDTVFAENLGV
CG114784-01	HLYGIQRGDIVIAKSPSDPKSNICKKVIGLEGDKILATSPSDFFKSRSYVPVGHVWLE
Protein Sequence	GDNLQNSTDSRYYGPIPYRLIRGRIFFKIWPLSDFEFLRASSNGHRFSDDW

[0412] Further analysis of the NOV18a protein yielded the following properties shown in Table 18B.

TABLE 18B
Protein Sequence Properties NOV18a
PSort     0.6400 probability located in microbody (peroxisome);
analysis: 0.4500 probability located in cytoplasm; 0.1610
          probability located in lysosome (lumen); 0.1000
          probability located in mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0413] A search of the NOV18a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 18C.

TABLE 18C
Geneseq Results for NOV18a
		NOV18a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Number	[Patent #, Date]	Residues	Portion	Value
ABG08149	Novel human diagnostic protein	1 . . . 166	144/166 (86%)	3e−81
	#8140 - Homo sapiens, 166 aa.	1 . . . 166	148/166 (88%)
	[WO200175067-A2, 11 OCT. 2001]
AAB47563	Protease PRTS-5 - Homo sapiens, 166	1 . . . 166	144/166 (86%)	3e−81
	aa. [WO200171004-A2, 27 SEP. 2001]	1 . . . 166	148/166 (88%)
ABG08149	Novel human diagnostic protein	1 . . . 166	144/166 (86%)	3e−81
	#8140 - Homo sapiens, 166 aa.	1 . . . 166	148/166 (88%)
	[WO200175067-A2, 11 OCT. 2001]
ABB64326	Drosophila melanogaster polypeptide	5 . . . 150	71/160 (44%)	1e−33
	SEQ ID NO 19770 - Drosophila	3 . . . 162	94/160 (58%)
	melanogaster, 166 aa.
	[WO200171042-A2, 27 SEP. 2001]
AAB74688	Human protease and protease	108 . . . 166	53/59 (89%)	2e−25
	inhibitor PPIM-21 - Homo sapiens, 94	36 . . . 94	54/59 (90%)
	aa. [WO200110903-A2, 15 FEB . 2001]

[0414] In a BLAST search of public sequence datbases, the NOV18a protein was found to have homology to the proteins shown in the BLASTP data in Table 18D.

TABLE 18D
Public BLASTP Results for NOV18a
		NOV18a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96LU5	CDNA FLJ25059 fis, clone	1 . . . 166	144/166 (86%)	8e−81
	CBL04610 - Homo sapiens (Human),	1 . . . 166	148/166 (88%)
	166 aa.
Q9CQU8	1500034J20Rik protein	1 . . . 166	141/166 (84%)	3e−79
	(2610528O17Rik protein) (RIKEN	1 . . . 166	145/166 (86%)
	cDNA 1500034J20 gene) - Mus
	musculus (Mouse), 166 aa.
Q96SH9	DJ1137O17.1 (Similar to putative	1 . . . 144	124/144 (86%)	5e−68
	mitochondrial inner membrane	1 . . . 144	128/144 (88%)
	protease subnunit 2) - Homo sapiens
	(Human), 144 aa (fragment).
Q9VXR8	CG9240 protein - Drosophila	5 . . . 150	71/160 (44%)	3e−33
	melanogaster (Fruit fly), 166 aa.	3 . . . 162	94/160 (58%)
Q8SZ24	RE22928p - Drosophila melanogaster	5 . . . 150	71/160 (44%)	7e−33
	(Fruit fly), 166 aa.	3 . . . 162	93/160 (57%)

[0415] PFam analysis predicts that the NOV18a protein contains the domains shown in the Table 18E.

TABLE 18E
Domain Analysis of NOV18a
		Identities/
	NOV18a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
Peptidase_S26	42 . . . 98	23/70 (33%)	1.4e−09
		44/70 (63%)
Peptidase_S26	117 . . . 139	12/24 (50%)	0.011
		16/24 (67%)

Example 19

[0416] The NOV19 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 19A.

TABLE 19A
NOV19 Sequence Analysis
	SEQ ID NO:93	725 bp
NOV19a,	GTCGACTTCGGCGGGAGCCAAGGTGAGAAAGGCCCACCTGTGTCCTGGTTGAGGGTCT
CG4886-01 DNA	CCAGGGTTCTTTGGGGCCCGAGGCCAATGGTGGCAGAGTCTACATAGAACTATGCTTC
Sequence	GTGGTGCTCTGGGGAAAACCTTTCGACTTGTTGGCTATACTATTCAGTATGGCTGTAT
	AGCTCATTGTGCTTCTGAATACGTTGGTGGTGTTGTCATGTGTTCTGGACCATCAATG
	GAGCCTACAATTCAAAATTCAGATACTGTCTTTGCAGAAAATCTTAGTCGACATTTTT
	ATGGTATCCAAAGAGGTGACATTGTGATTGCAAAAAGCCCAAGTGATCCAACATCAAA
	TATTTGTAAAAGAGTAACTGGTTTGGAAGGAGACAAAATCCTCACCACTAGTCCATCA
	GATTTCTTTAAAAGCTACAGTTATGTCCCAGTGGGTCATGTTTGGTTAGAAGGTGATA
	ATCTACAGAATTCTACAGATTCCAGGTGCTATGGACCTATTCCATATGGACTAATAAG
	AGGACGAATCTTCTTTAAGATTTGGCCTCTGAGTGATTTTGGATTTTTACGTGCCAGC
	CCTAATGGCCACAGATTTTCTGATGATTAGTAAGCATTTATTCTTTTGACTTGATTAT
	TGTCTCCTTTTCATGTGAATTTATTACTCCCGTTGAAACCGTGTACTTACCAATAAAC
	TATTTGCTATTCAAAAAAAAAAAAAAAAA
	ORF Start: ATG at 110		ORF Stop: TAG at 608
	SEQ ID NO:94	166 aa	MW at 18358.6 Da
NOV19a,	MLRGALGKTFRLVCYTIQYGCIAHCASYVGGVVMCSGPSMEPTIQNSDTVFAENLSR
CG114886-01	HFYGIQRGDIVIAKSPSDPTSNICKRVTGLEDKILTTSPSDFFKSYSYVPVGHVWLE
Protein Sequence	GDNLQNSTDSRCYGPIPYGLIRGRIFFKILWPLSDFGFLRASPNGHRFSDD

[0417] Further analysis of the NOV19a protein yielded the following properties shown in Table 19B.

TABLE 19B
Protein Sequence Properties NOV19a
PSort     0.6400 probability located in microbody (peroxisome);
analysis: 0.4500 probability located in cytoplasm; 0.1659 probability
          located in lysosome (lumen); 0.1000 probability located in
          mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0418] A search of the NOV19a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 19C.

TABLE 19C
Geneseq Results for NOV19a
		NOV19a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABG08149	Novel human diagnostic protein	1 . . . 166	159/166 (95%)	4e−93
	#8140 - Homo sapiens, 166 aa.	1 . . . 166	161/166 (96%)
	[WO200175067-A2, 11 OCT. 2001]
AAB47563	Protease PRTS-5 - Homo sapiens, 166	1 . . . 166	159/166 (95%)	4e−93
	aa. [WO200171004-A2, 27 SEP. 2001]	1 . . . 166	161/166 (96%)
ABG08149	Novel human diagnostic protein	1 . . . 166	159/166 (95%)	4e−93
	#8140 - Homo sapiens, 166 aa.	1 . . . 166	161/166 (96%)
	[WO200175067-A2, 11 OCT. 2001]
ABB64326	Drosophila melanogaster polypeptide	6 . . . 150	73/159 (45%)	1e−36
	SEQ ID NO 19770 - Drosophila	4 . . . 162	95/159 (58%)
	melanogaster, 166 aa.
	[WO200171042-A2, 27 SEP. 2001]
AAB74688	Human protease and protease	108 . . . 166	57/59 (96%)	2e−29
	inhibitor PPIM-21 - Homo sapiens, 94	36 . . . 94	58/59 (97%)
	aa. [WO200110903-A2, 15 FEB. 2001]

[0419] In a BLAST search of public sequence datbases, the NOV19a protein was found to have homology to the proteins shown in the BLASTP data in Table 19D.

TABLE 19D
Public BLASTP Results for NOV19a
		NOV19a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96LU5	CDNA FLJ25059 fis, clone	1 . . . 166	159/166 (95%)	1e−92
	CBL04610 - Homo sapiens (Human),	1 . . . 166	161/166 (96%)
	166 aa.
Q9CQU8	1500034J20Rik protein	1 . . . 166	151/166 (90%)	2e−86
	(2610528O17Rik protein) (RIKEN	1 . . . 166	152/166 (90%)
	cDNA 1500034J20 gene) - Mus
	musculus (Mouse), 166 aa.
Q96SH9	DJ1137O17.1 (Similar to putative	1 . . . 144	137/144 (95%)	5e−78
	mitochondrial inner membrane	1 . . . 144	139/144 (96%)
	protease subnunit 2) - Homo sapiens
	(Human), 144 aa (fragment).
Q9VXR8	CG9240 protein - Drosophila	6 . . . 150	73/159 (45%)	3e−36
	melanogaster (Fruit fly), 166 aa.	4 . . . 162	95/159 (58%)
Q8SZ24	RE22928p - Drosophila	6 . . . 150	73/159 (45%)	6e−36
	melanogaster (Fruit fly), 166 aa.	4 . . . 162	94/159 (58%)

[0420] PFam analysis predicts that the NOV19a protein contains the domains shown in the Table 19E.

TABLE 19E
Domain Analysis of NOV19a
		Identities/
	NOV19a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
Peptidase_S26	38 . . . 98	25/74 (34%)	3.5e−14
		47/74 (64%)

Example 20

[0421] The NOV20 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 20A.

TABLE 20A
NOV20 Sequence Analysis
	SEQ ID NO:95	6149 bp
NOV20a,	ACCGTGGTGCCGAGTGCCTGCTGCCTTGGGCCGCCTTGAACCTCCAGGGTTTCCAGCT
CG115411-01 DNA	CCTCCTCCTTCACCCCAGTGCCACTGCCATGATGGATGTGAGTGAACTTGGGGAGTCT
Sequence	GCCCGCTACCTCCGCCAGGGCTACCAGGAGATGACGAAGGTGCACACTATCCCATGGG
	ACGGGAAGAAGCGAGTCTGGGTGCCTGATGAACAGGACGCCTACGTGGAGGCCGAGGT
	CAAGTCGGAGGCTACCGGGGGCAGAGTCACCGTGGAGACCAAAGACCAGAAGGTGCTG
	ATGGTGCGTGAACCCGAGCTGCAGCCCATGAACCCGCCTCGCTTCGACTTACTGGAGG
	ACATGGCCATGATGACGCACCTGAACGAGGCCTCTGTGCTGCACAACCTGCGCCAGCG
	CTATGCCCGCTGGATGATCTATACCTACTCAGGCCTCTTCTGTGTCACCATCAACCCC
	TACAAATGGCTCCCAGTCTATACGGCCTCCGTAGTGGCTGCTTACAAGGGAAAGCGCC
	GCTCAGATTCCCCGCCCCATATATATGCGGTGGCGGACAACGCCTACAACGACATGCT
	GCGCAACCGAGACAACCAGTCCATGCTGATCACCGGAGAGTCGGGGGCCGGTAAGACG
	GTTAACACCAAGCGGGTCATTCAGTACTTTGCCATCGTCGCTGCCCTGCGAGACGGGC
	CGGGCAAGAAGGCCGGCACCCTTGAGGATCAAATCATCGAGGCCAACCCTGCCATGGA
	GGCCTTTGGCAACGCCAAGACCCTGAGGAATGATAACTCCTCCCGCTTTGGCAAGTTC
	ATCCGCATTCACTTTGGTCCCTCTGGGAAGCTGGCATCCGCGGATATTGACAGCTATC
	TCCTGGAGAAGTCGCGGGTGATCTTCCAGTTGCCTGGTGAGCGCAGCTACCATGTCTA
	CTACCAGATCCTCTCAGCGAGGAAGCCAGAGCTGCAGGACATGCTGCTTCTGTCTATG
	AACCCCTATGACTACCACTTCTGCAGCCAGGGCGTCATCACCGTGGACAACATGAATG
	ATGGGGAGGAGCTCATCGCCACCGACCATGCCATGGACATCCTAGGCTTCAGCGTGGA
	TGAGAAATGTGCCTGCTATAAGATCGTGGGCGCCCTCCTGCACTTTGGCAACATGAAG
	TTCAAGCAGAAGCAGCGGGAGGAGCAGGCGGAGGCCGATGGCACTGAGAGTGCTGACA
	AGGCTGCCTACCTGATGGGGGTCAGCAGTGGGGACCTCCTCAAAGGCCTTTTGCACCC
	CCGGGTGCGTGTAGGGAACGAGTACGTGACCAAGGGCCAGAGTGTGGAGCAGGTGGTG
	TTTGCTGTGGGGGCTCTGGCCAAGGCCACCTATGACCGGCTGTTCAGGTGGCTGGTGT
	CTCGGATCAACCAGACCCTGGACACAAAGCTGCCCCGGCAGTTCTTCATCGGGGTTCT
	GGACATCGCTGGGTTTGAGATCTTTGAGTTCAACAGCTTCGAACAGCTGTGCATCAAC
	TTCACCAATGAGAAATTGCAGCAGTTCTTCAACCAGCACATGTTTGTGCTGGAGCAGG
	AGGAGTACAAGCGGGAGGGCATCGACTGGGTCTTCATCGACTTCGGCCTTGACCTGCA
	GCCTTGCATCCACCTCATCGAGAAGCCACTGGGCATCCTGTCCATCCTGGAGGAGGAA
	TGCATGTTCCCCAAGGCCTCAGACGCCAGCTTCCGGGCCAAGCTCTACGACAACCACG
	CGGGGAAGTCACCCAATTTCCAGCAGCCTCGGCCTGACAAGAAGCGCAAGTACCAGGC
	CCACTTCGAGGTGGTCCACTACGCAGGCGTGGTGCCTTACAGCATTGTGGGCTGGCTG
	GAGAAAAACAAGGATCCCCTGAATGAGACCGTGGTCCCCATCTTCCACAAGTCACAGA
	ATAGGCTCCTGGCGACTCTCTATGAGAATTATGCGGGCTCCTGCTCCACTGAGCCCCC
	CAAGTCTGGGGTGAAAGAGAAGCGTAAGAAGGCAGCATCGTTCCAGACGGTGTCCCAG
	CTGCACAAGCAGAACCTCAACAAGCTGATGACCAACCTGCGGGCCACACAGCCCCACT
	TCGTCCGCTGCATTGTCCCCAACGAGAACAAAACCCCAGGGGTCATGGATGCCTTCTT
	GGTGCTACACCAGCTCCGCTGCAATGGGGTCCTGGAGGGGATCCGGATCTGCCGCCAA
	GGGTTCCCCAACAGGTTGCTCTACACCGACTTCCGGCAGCGGTACCGTATCCTGAAACC
	CCAGTGCCATCCCGCATGACACCTTCATGGACAGCAGGAAGGCCACAGAGAAACTGCT
	GGGCTCGCTGGACTTGGATCACACCCAGTACCAGTTTGGCCACACCAAGGTGTTCTTC
	AAGGCTGGGCTTCTAGGCGTCCTGGAAGAGCTCCGTGACCAGCGCCTGGCCAAGGTGC
	TGACGCTGCTGCAGGCGCGGAGCCGTGGCCGCCTCATGCGCCTTGAGTACCAGCGCCT
	GCTGGGAGGCAGGGATGCGCTGTTCACCATCCAGTGGAACATCCCTGCCTTCAATGCC
	GTCAAGAACTGGTCATGGATGAAGCTCTTTTTCAAGATGAAGCCGCTGCTGCGCTCGG
	CGCAGGCTGAGCAGGAGCTGCCGGCCCTGCGGGCAGAGCTGCGGGGGTTGCGAGGGGC
	GCTCGCTGCGGCCGAGGCCAAGCGCCACGAACTGGAGGACACGCACGTCAGCATCACC
	CAGGAGAAGAATGACCTGGCCCTGCAGCTGCAGGCTGAGCAGGACAACCTGGCAGATG
	CCGAGGAGCGCTGCCACTTGCTGATCAAGTCCAAGGTGCAGCTCGAGGGGAAGGTGAA
	GGAGCTGAGTGAGCGGCTGGAGGATGAGGAGGAGGTGAACGCTGACCTGGCCGCCCGC
	CGGCGCAAGCTGGAGGACGAGTGCACGGAGCTCAAGAAGGACATTGATGACCTGAAGC
	TGACACTGGCCAAAGCTGAGAAGGAGAAGCAAGCCACTGAGAACAAGGTGAAGAACCT
	GACGGAAGAGATGGCTGCGCTGGACGAGTCAGTGGCCCGGCTGACCAAGGAGAAGAAG
	GCGTTGCAGGAGGCCCACCAACAGGCCCTGGGTGACCTGCAGGCCGAGGAGGACCGTG
	TGAGCGCGCTGACCAAGGCCAAGCTCCGGCTGGAGCAACAGGTGGAGGACCTGGAATG
	CTCCCTGGAGCAGGAGAAGAAGCTGCGCATGGACACGGAGCGGGCCAAGCGCAAGCTG
	GAGGGTGACCTGAAGCTGACGCAGGAGTCGGTGGCTGATGCTGCTCAAGACAAGCAGC
	AGCTGGAGGAGAAGCTCAAGAAGAAGGACTCCGAGCTGAGCCAGCTGAGCCTGCGGGT
	GGAAGACGAGCAGCTCTTGGGGGCCCAGATGCAGAAGAAGATCAAGGAGCTGCACGCT
	CGGGCGGAGGAGCTGGAAGAGGAGCTGGAGGCAGAGCGGGCAGCCCGCGCCCGCGTGG
	AGAAGCAGCGTGCAGAGGCGGCGCGGGAGCTGGAGGAGCTGAGCGAGCGGCTCGAGGA
	GGCAGGCGGCCCATCCGCGGGGCAGCGCGAGGGCTGCCGCAAGCGGGAGGCGGAGCTG
	GGGAGGCTGCGGCGGGAGCTGGAGGAGGCGGCGCTGCGGCACGAGGCCACAGTGGCGG
	CACTGCGGCGCAAGCAGGCGGAGGGCGCGGCGGAGCTGGGGGAGCAGGTGGACAGCCT
	GCAGCGGGTGCGGCAGAAGCTGGAGAAGGAGAAGAGTGAGCTGCGCATGGAGGTGGAC
	GACCTGGCTGCCAACGTGCAGACTCTGACCCGCGCCAAGGCCACTGCAGAGAAGCTGT
	GCCGGACCTATGAGGATCAGCTAAGCGAGGCCAAGATCAAGGTGGAGGAGCTGCAGCG
	GCAGCTGGCGGACGCAAGCACGCAGCGTGGGCGACTACAGACGGAAAGCGGGGAGCTG
	AGTCGCCTGCTAGAGGAGAAGGAGTGTCTGATCAGTCAGCTGAGCCGTCGAAAGGCCC
	TGGCCGCCCAAAGCCTGGAAGAGTTGCGGCGCCAGCTAGAGGAGGAAAGCAAGGCCAA
	GAGTGCCCTGGCCCACGCCGTGCAGGCTCTGCGGCACGACTGTGACCTCCTGCGGGAG
	CAACACGAGGAGGAGGCTGAGGCCCAGGCTGAGCTGCAGCGGCTGCTGTCCAAGGCCA
	ATGCCGAGGTGGCCCAGTGGAGGAGCAAGTACGAAGCACATGCCATCCAGAGGACCCA
	GGAGCTGGAGGAGGCCAAAAAAAAGCTGGCACTGCGGCTGCAGGAGGCAGAGGACGGC
	GTGGAGGCTGCCAACGCCAAGTGCTCATCGTTGGAGAAGGCCAAGCTGCGGCTACAGA
	CAGAGTCAGAGGATGTAACCCTGGAGCTGGAGCGGGCGACCTCAGCAGCTGCTGCGCT
	GGACAAGAAGCAGCGGCACTTGGAACGGGCACTGGAGGAACGGCGGCGCCAGCAGGAG
	GAGATGCAGCGGGAGCTGGAGGCGGCACAGAGGGAGTCCCGTGGCCTGGGCACCGAGC
	TCTTCCGGCTGCGGCACGGCCACGAGGAGGCACTTGAAGCCCTGGAGACGCTCAAGCG
	GGAGAACAAGAACCTGCAGGAGGAGATCAGCGACCTCACAGACCAGGTGAGTCTCAGT
	GGGAAGAGCATCCAGGAACTGGAGAAAACCAAGAAGGCGCTGGAAGGCGAGAAGAGTG
	AGATCCAGGCTGCACTGCAGGAGGCAGAGGGGGCCCTGGAGCTGGAGGAGACCAAGAC
	GCTGCGGATCCAGCTGGAGCTCTCCCAGGTCAAAGCAGAAGTGGACCGGAAGCTGGCA
	GAGAAAGACGAGGAGTGCGCTAACCTGAGGCGCAACCACCAGCGAGCTGTGGAGTCCC
	TGCAGGCCTCCCTGGATGCAGAGACACGGGCCCGCAATGAGGCGCTGCGGCTCAAGAA
	GAAGATGGAGGGTGACCTCAACGACCTGGAGCTGCAGCTGGGCCATGCCACCCGTCAG
	GCCACAGAGGCCCAGGCTGCCACGCGGCTGATGCAGGCACAGCTCAAGGACGAGCAGG
	CAGGGCGGGACGAGGAGCAGCGGCTGGCAGCTGAGCTCCACGAGCAGGCGCAGCCTCT
	GGAGCGCCGGGCCTCGCTGCTGGCTGCGGAGCTGGAGGAGCTGCGGGCTGCCCTGGAG
	CAGGGCGAGCGCACCCGGCGACTGGCAGAGCAGGAGCTTTTGGAGGCCACCGAGCGCC
	TCAACCTTCTGCATTCGCAGAACACAGGCCTCCTAAACCAGAAGAAGAAGCTGGAGGC
	GGACTTGGCCCAGCTGAGCGGGGAGGTGGAGGAGGCTGCACAGGAGAGGCGGGAGGCT
	GAGGAGAACGCCAAAAAGGCCATCACTGATGCGGCCATGATGGCCGAGGAGCTGAAGA
	AGGAGCAGGACACAAGTGCACACCTGGAACGGATGAAGAAGACGCTGGAGCAGACGGT
	GCGCGACCTCCAGGCCCGCCTTGAGGAGGCAGAACAGGCCGCCCTCCGTGGCCGGAAG
	AAGCAGGTGCAGAAGCTGGAGGCCAAGGTACGGGAGCTGGAGGCTGAGCTTGATGCAG
	AGCAGAAGAAGCACGCCGAGGCCCTTAAGGGCGTGCGCAAGCATGAGCGCCGTGTCAA
	GGAGCTCGCATACCAGGCCGAGGAGGACAGGAAGAACCTGGCTCGCATGCAGGACCTG
	GTGGACAAGCTGCAGAGCAAGGTCAAGAGCTACAAGCGCCAGTTTGAGGAGGCGGAGG
	CTTATGCGAAGGCCAGGCAGGAGCAGCAGGCCAACACCAACCTGGCCAAGTATCGCAA
	GGCCCAGCACGAGCTGGATGATGCGGAGGAGCGGGCAGACATGGCGGAAACCCACGCC
	AACAAGCTGCGGGCACGGACCCGGGACGCCCTGGGCCCCAAGCACAAGGAGTGACGGC
	CTGACCCCCTGGGCTCTAAAGAGGAATGTCTGCTGTTGCACATCTGGCTGAGGCCACC
	TGCCCCGATCCTGCCATCTCTGCATCGCCCCCTGCTGCCTTCGGCCTTCCCTGGGCCC
	TGAATAAACACCACAGCCAGTTTCCTTCTCATTCTTTTCTTTGGGGTTCAGGAGGAAA
	AACACAGTCCTAGGGACAAAAGCCAGGTCCACAGCAGTCATTTTTAAAATAAAGTTAT
	T
	ORF Start: ATG at 87		ORF Stop: TGA at 5910
	SEQ ID NO:96	1941 aa	MW at 221456.2 Da
NOV20a,	MMDVSELGESARYLRQCYQEMTKVHTIPWDGKKRVWVPDEQDAYVEAEVKSEATGGRV
CG115411-01	TVETKDQKVLMVREAELQPMNPPRFDLLEDMAMMTHLNEASVLHNLRQRYARWMIYTY
Protein Sequence	SGLFCVTTNPYKWLPVYTASVVAAYKGKRRSDSPPHIYAVADNAYNDMLRNRDNQSML
	ITGESGAGKTVNTKRVIQYFAIVAALGDGPGKKAGTLEDQIIEANPAMEAFGNAKTLR
	NDNSSRFGKFIRIHFGPSGKLASADIDSYLLEKSRVIFQLPGERSYHVYYQILSGRKP
	ELQDMLLLSMNPYDYHFCSQGVITVDNMNDGEELIATDHAMDILGFSVDEKCACYKIV
	GALLHFGNMKFKQKQREEQAEADGTESADKAAYLMGVSSGDLLKGLLHPRVRVGNEYV
	TKGQSVEQVVFAVGALAKATYDRLFRWLVSRINQTLDTKLPRQFFIGVLDIAGFEIFE
	FNSFEQLCINFTNEKLQQFFNQHMFVLEQEEYKREGIDWVFIDFGLDLQPCIDLIEKP
	LGILSILEEECMFPKASDASFRAKLYDNHAGKSPNFQQPRPDKKRKYQAHFEVVHYAG
	VVPYSIVGWLEKNKDPLNETVVPIFQKSQNRLLATLYENYAGSCSTEPPKSGVKEKRK
	KAASFQTVSQLHKENLNKLMTNLRATQPHFVRCIVPNENKTPGVMDAFLVLHQLRCNG
	VLEGIRICRQGFPNRLLYTDFRQRYRILNPSAIPDDTFMDSRKATEKLLGSLDLDHTQ
	YQFGHTKVFFKAGLLGVLEELRDQRLAKVLTLLQARSRGRLMRLEYQRLLGGRDALFT
	IQWNIRAFNAVKNWSWMKLFFKMKPLLRSAQAEEELAALRAELRGLRGALAAAEAKRQ
	ELEETHVSITQEKNDLALQLQAEQDNLADAEERCHLLIKSKVQLEGKVKELSERLEDE
	EEVNADLAARRRKLEDECTELKKDIDDLKLTLAKAEKEKQATENKVKNLTEEMAALDE
	SVARLTKEKKALQEAHQQALGDLQAEEDRVSALTKAKLRLEQQVEDLECSLEQEKKLR
	MDTERAKRKLEGDLKLTQESVADAAQDKQQLEEKLKKKDSELSQLSLRVEDEQLLGAQ
	MQKKIKELQARAEELEEELEAERAARARVEKQRAEAARELEELSERLEEAGGASAGQR
	EGCRKREAELGRLRRELEEAALRHEATVAALRRKQAEGAAELGEQVDSLQRVRQKLEK
	EKSELRMEVDDLAANVETLTRAKASAEKLCRTYEDQLSEAKIKVEELQRQLADASTQR
	GRLQTESGELSRLLEEKECLISQLSRGKALAAQSLEELRRQLEEESKAKSALAHAVQA
	LRHDCDLLREQHEEEAEAQAELQRLLSKANAEVAQWRSKYEADAIQRTEELEEAKKKL
	ALRLQEAEEGVEAANAKCSSLEKAKLRLQTESEDVTLELERATSAAAALDKKQRHLER
	ALEERRRQEEEMQRELEAAQRESRGLGTELFRLRHGHEEALEALETLKRENKNLQEEI
	SDLTDQVSLSGKSIQELEKTKKALECEKSEIQAALEEAEGALELEETKTLRIQLELSQ
	VKAEVDRKLAEKDEECANLRRNHQRAVESLQASLDAETRARNEALRLKKKMEGDLNDL
	ELQLGHATRQATEAQAATRLMQAQLKEEQAGRDEEQRLAAELHEQAQALERRASLLAA
	ELEELRAALEQGERSRRLAEQELLEATERLNLLHSQNTGLLNQKKKLEADLAQLSGEV
	EEAAQERREAEEKAKKAITDAAMMAEELKKEQDTSAHLERMKKTLEQTVRELQARLEE
	AEQAALRGGKKQVQKLEAKVRELEAELDAEQKKHAEALKGVRKHERRVKELAYQAEED
	RKNLARMQDLVDKLQSKVKSYKRQFEEAEAYAKARQEQQANTNLAKYRKAQHELDDAE
	ERADMAETQANKLRARTRDALGPKHKE

[0422] Further analysis of the NOV20a protein yielded the following properties shown in Table 20B.

TABLE 20B
Protein Sequence Properties NOV20a
PSort     0.9600 probability located in nucleus; 0.3000 probability
analysis: located in microbody (peroxisome); 0.1000 probability located
          in mitochondrial matrix space; 0.1000 probability located in
          lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0423] A search of the NOV20a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 20C.

TABLE 20C
Geneseq Results for NOV20a
		NOV20a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABG21233	Novel human diagnostic protein	3 . . . 1933	1283/1944 (65%)	0.0
	#21224 - Homo sapiens, 1948 aa.	9 . . . 1939	1604/1944 (81%)
	[WO200175067-A2, 11 OCT. 2001]
ABG21233	Novel human diagnostic protein	3 . . . 1933	1283/1944 (65%)	0.0
	#21224 - Homo sapiens, 1948 aa.	9 . . . 1939	1604/1944 (81%)
	[WO200175067-A2, 11 OCT. 2001]
AAW54241	Rattus norvegicus mutant alpha-	10 . . . 1940	1273/1936 (65%)	0.0
	myosin heavy chain - Rattus	11 . . . 1881	1580/1936 (80%)
	norvegicus, 1886 aa. [WO9813476-
	A1, 02 APR. 1998]
ABB71125	Drosophila melanogaster	28 . . . 1932	1021/2013 (50%)	0.0
	polypeptide SEQ ID NO 40167 -	31 . . . 2029	1366/2013 (67%)
	Drosophila melanogaster, 2067 aa.
	[WO200171042-A2, 27 SEP. 2001]
AAM41000	Human polypeptide SEQ ID NO	29 . . . 1932	776/1919 (40%)	0.0
	5931 - Homo sapiens, 1988 aa.	41 . . . 1941	1158/1919 (59%)
	[WO200153312-A1, 26 JUL. 2001]

[0424] In a BLAST search of public sequence datbases, the NOV20a protein was found to have homology to the proteins shown in the BLASTP data in Table 20D.

TABLE 20D
Public BLASTP Results for NOV20a
		NOV20a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9H430	DJ56N5.1.1 (Continues in	67 . . . 1941	1868/1889 (98%)	0.0
	Em:AL133324 as dJ1161H23.3) -	1 . . . 1889	1869/1889 (98%)
	Homo sapiens (Human), 1889 aa
	(fragment).
Q9P216	KIAA1512 protein - Homo sapiens	242 . . . 1941	1691/1700 (99%)	0.0
	(Human), 1692 aa (fragment).	1 . . . 1692	1692/1700 (99%)
Q8UWA0	Myosin heavy chain - Gallus gallus	1 . . . 1940	1538/1948 (78%)	0.0
	(Chicken), 1941 aa.	3 . . . 1941	1758/1948 (89%)
Q9IBD4	Myosin heavy chain - Gallus gallus	1 . . . 1933	1403/1940 (72%)	0.0
	(Chicken), 1937 aa.	1 . . . 1927	1686/1940 (86%)
Q9H1D5	Beta-myosin heavy chain - Homo	3 . . . 1933	1341/1937 (69%)	0.0
	sapiens (Human), 1935 aa.	5 . . . 1926	1644/1937 (84%)

[0425] PFam analysis predicts that the NOV20a protein contains the domains shown in the Table 20E.

TABLE 20E
Domain Analysis of NOV20a
		Identities/
	NOV20a	Similarities for	Expect
Pfam Domain	Match Region	the Matched Region	Value
Myosin_N	32 . . . 76	19/48 (40%)	1.1e−13
		38/48 (79%)
myosin_head	86 . . . 765	385/738 (52%)	0
		615/738 (83%)
Myosin_tail	1067 . . . 1934	512/872 (59%)	0
		758/872 (87%)

Example 21

[0426] The NOV21 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 21A.

TABLE 21A
NOV21 Sequence Analysis
	SEQ ID NO:97	1194 bp
NOV21a,	CTGCACGCCTTCTACTACTCGTGGTACGGGAGCCCGCGGCGCGAGGGCCACTACATTC
CG116270-01 DNA	ACTGGGACCACGTCATGGTGCCGCACTGGGACCCCAAGATCTCGGCCAGCTACCCCCG
Sequence	CGGCCGCCACAGCCCCCCAGACGACTTGGGCTCCAGCTTCTACCCGGAGCTGGGGCCC
	TACAGCTCCCGGGACCCCGAAGTGCTGCGGGAGCATATGACCCAGCTCAAGGAAGCCG
	CCATCGGCGTCCTGGTCCTGTCCTGGTACCCACCTGGCATGGCTGATGATAACGGGGA
	GCCCTCAGATGACCTGGTGCCCGCCATTCTGGACACCGCCCATCAGTACAGCATCCAG
	GTGGCCTTCCACATCCAACCCTACAAGGGCCGGGATGACATCACTGTACATGACAACA
	TCAAGTACATCATTGACAGGTATGGCTCCCATGGTGCATTTTACCGCTATAAGAACAG
	CATGGGCAAGAGCCTCCCACTCTTTTATATCTACGACTCATACCTGACGTCCCCTGAG
	GCCTGGGCCCACCTCCTGACACCAAACGGGCCCCATTCGATCCGCAACACGCCCTACG
	ATGGGGTCTTCATAGCGCTGCTGGTGGAGGAGGGCCACACCCACGATATCCTGGCCGC
	CGGATTTGACGGCATGTACACCTACTTTGCCTCCAATGGTTTCTCCTTTGGTTCTTCC
	CATCAGAACTGGAAAGCTGTGAAGAACTTTTGTGATGCCAACAACCTCATGTTCATCC
	CCAGTGTGGGGCCTGGCTACATAGACACCAGCATTCGGCCCTGGAACAACCACAATAC
	GCGCAACAGGGTCAATGGCAAGTACTATGAGACGGCCCTGCAGGCGGCCCTGACAGTG
	AGGCCCGAGATCGTTTCCATTACCTCCTTCAATGAGTGGCACGAGGGCACCCAGATTG
	AGAAGGCCATTCCCAAGAAGACACCCACCCGCCTGTATTTGGACTACCTGCCTCACCA
	GCCCAGCCTGTACCTGGAGCTGACACGCCGCTGGGCGGAGCACTTCATCAAAGAGAAG
	GAGCAGTGGCTCATGTGAGGGGCCTGTAAATGGGCGTGAGGTGCTGATGTCCTTGCCT
	TGCTGGAAGATGTCACCATGTGGGGTTCAGCTGAGGTTGTAGCCACTCACTCGTTCCC
	AGGTCAGAGGTCAGCAGATGGGTGTTTCTGGGTG
	ORF Start: ATG at 73		ORF Stop: TGA at 1060
	SEQ ID NO:98	329 aa	MW at 37656.9 Da
NOV21a,	MVPHWDPKISASYPRGRHSPPDDLGSSFYPELGPYSSRDPEVLREHMTQLKEAAIGVL
CG116270-01	VLSWYPPGMADDNGEPSDDLVPAILDTAHQYSIQVAFHIQPYKGRDDITVHDNIKYII
Protein Sequence	DRYGSHGAFYRYKNSMGKSLPLFYIYDSYLTSPEAWAHLLTPNGPHSIRNTPYDGVFI
	ALLVEEGHTHDILAAGFDGMYTYFASNGFSFGSSHQNWKAVKNFCDANNLMFIPSVGP
	GYIDTSIRPWNNHNTRNRVNGKYYETALQAALTVRPEIVSITSFNEWHEGTQIEKAIP
	KKTPTRLYLDYLPHQPSLYLELTRRWAEHFIKEKEQWLM

[0427] Further analysis of the NOV21a protein yielded the following properties shown in Table 21B.

TABLE 21B
Protein Sequence Properties NOV21a
PSort     0.7480 probability located in microbody (peroxisome); 0.2256
analysis: probability located in lysosome (lumen); 0.1000 probability
          located in mitochondrial matrix space; 0.0000 probability
          located in endoplasmic reticulum (membrane)
SignalP   Cleavage site between residues 69 and 70
analysis:

[0428] A search of the NOV21a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 21C.

TABLE 21C
Geneseq Results for NOV21a
		NOV21a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB95204	Human protein sequence SEQ ID	47 . . . 329	187/283 (66%)	e−120
	NO: 17303 - Homo sapiens, 290 aa.	1 . . . 283	234/283 (82%)
	[EP1074617-A2, 07 FEB. 2001]
AAE04255	Human gene 4 encoded secreted	7 . . . 268	176/262 (67%)	e−112
	protein fragment, SEQ ID NO: 116 -	1 . . . 262	218/262 (83%)
	Homo sapiens, 264 aa.
	[WO200136432-A2, 25 MAY 2001]
AAE04254	Human gene 4 encoded secreted	7 . . . 268	176/262 (67%)	e−112
	protein fragment, SEQ ID NO: 115 -	5 . . . 266	218/262 (83%)
	Homo sapiens, 268 aa.
	[WO200136432-A2, 25 MAY 2001]
AAM47969	Human endomannosidase 25 - Homo	108 . . . 329	150/222 (67%)	8e−95
	sapiens, 229 aa. [CN1315551-A,	1 . . . 222	185/222 (82%)
	03 OCT. 2001]
AAE04253	Human gene 4 encoded secreted	47 . . . 268	149/222 (67%)	5e−93
	protein fragment, SEQ ID NO: 114 -	1 . . . 222	184/222 (82%)
	Homo sapiens, 224 aa.
	[WO200136432-A2, 25 MAY 2001]

[0429] In a BLAST search of public sequence datbases, the NOV21a protein was found to have homology to the proteins shown in the BLASTP data in Table 21D.

TABLE 21D
Public BLASTP Results for NOV21a
		NOV21a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O35390	Endo-alpha-D-mannosidase - Rattus	1 . . . 324	219/324 (67%)	e−144
	norvegicus (Rat), 451 aa.	116 . . . 439	274/324 (83%)
Q96N42	CDNA FLJ31434 fis, clone	118 . . . 329	212/212(100%)	e−128
	NT2NE2000586, moderately similar	24 . . . 235	212/212 (100%)
	to Rattus norvegicus endo-alpha-D-
	mannosidase (Enman) mRNA - Homo
	sapiens (Human), 235 aa.
Q9H9D2	CDNA FLJ12838 fis, clone	47 . . . 329	187/283 (66%)	e−120
	NT2RP2003230, moderately similar	1 . . . 283	234/283 (82%)
	to Rattus norvegicus endo-alpha-D-
	mannosidase (Enman) mRNA - Homo
	sapiens (Human), 290 aa.
Q96G55	Similar to hypothetical protein	166 . . . 329	164/164 (100%)	2e−96
	FIJ12838 - Homo sapiens (Human,	4 . . . 167	164/164 (100%)
	167 aa (fragment).
Q8SYI8	RE57134p - Drosophila melanogaster	24 . . . 326	94/311 (30%)	4e−35
	(Fruit fly), 483 aa.	168 . . . 461	160/311 (51%)

[0430] PFam analysis predicts that the NOV21a protein contains the domains shown in the Table 21E.

TABLE 21E
Domain Analysis of NOV21a
		Identities/
	NOV21a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value

Example 22

[0431] The NOV22 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 22A.

TABLE 22A
NOV22 Sequence Analysis
	SEQ ID NO:99	4497 bp
NOV22a,	CTGGGCATTTATAACTAGATTCATTAAGGAATACAAAGAAAATACTTAAAGGGATCAA
CG118160-01 DNA	TAATGGTGTCTTCTGGTTGCAGAATGCGAAGTCTGTGGTTTATCATTGTAATCAGCTT
Sequence	CTTACCAAATACAGAAGGTTTCAGCAGAGCAGCTTTACCATTTGGGCTGGTGAGGCGA
	GAATTATCCTGTGAAGGTTATTCTATAGATCTGCGATGCCCGGGCAGTGATGTCATCA
	TGATTGAGAGCGCTAACTATGGTCGGACGGATGACAAGATTTGTGATGCTGACCCATT
	TCAGATGGAGAATACAGACTGCTACCTCCCCGATGCCTTCAAAATTATGACTCAAAGG
	TGCAACAATCGAACACAGTGTATAGTAGTTACTGGGTCAGATGTGTTTCCTGATCCAT
	GTCCTGGAACATACAAATACCTTGAAGTCCAATATGAATGTGTCCCTTACATTTTTGT
	GTGTCCTGGGACCTTGAAAGCAATTGTGGACTCACCATGTATATATGAAGCTGAACAA
	AAGGCGGGTGCTTGGTGCAAGGACCCTCTTCAGGCTGCAGATAAAATTTATTTCATGC
	CCTGGACTCCCTATCGTACCGATACTTTAATAGAATATGCTTCTTTAGAAGATTTCCA
	AAATAGTCGCCAAACAACAACATATAAACTTCCAAATCGAGTAGATGGTACTGGATTT
	GTGGTGTATGATGGTGCTGTCTTCTTTAACAAAGAAAGAACGAGGAATATTGTGAAAT
	TTGACTTGAGGACTAGAATTAAGAGTGGCGAGGCCATAATTAACTATGCCAACTACCA
	TGATACCTCACCATACAGATGGGGAGGAAAGACTGATATCGACCTAGCAGTTGATGAA
	AATGGTTTATGGGTCATTTACGCCACTGAACAGAACAATGGAATGATAGTTATTAGCC
	AGCTGAATCCATACACTCTTCGATTTGAAGCAACGTGGGAGACTGTATACGACAAACG
	TGCCGCATCAAATGCTTTTATGATATGCGGAGTCCTCTATGTGGTTAGGTCAGTTTAT
	CAAGACAATGAAAGTGAAACAGGCAAGAACTCAATTGATTACATTTATAATACCCGAT
	TAAACCGAGGAGAATATGTAGATGTTCCCTTCCCCAACCAGTATCAGTATATTGCTGC
	AGTGGATTACAATCCAAGAGATAACCAACTTTACGTGTGGAACAATAACTTCATTTTA
	CGATATTCTCTGGAGTTTGGTCCACCTGATCCTGCCCAAGTGCCTACCACAGCTGTGA
	CAATAACTTCTTCAGCTGAGCTGTTCAAAACCATAATATCAACCACAAGCACTACTTC
	ACAGAAAGGCCCCATGAGCACAACTGTAGCTGGATCACAGGAAGGAAGCAAAGGGACA
	AAACCACCTCCAGCAGTTTCTACAACCAAAATTCCACCTATAACAAATATTTTTCCCC
	TGCCAGAGAGATTCTGTGAAGCATTAGACTCCAAGGGGATAAAGTGGCCTCAGACACA
	AAGGGGAATGATGGTTGAACGACCATGCCCTAAGGGAACAAGAGGAACTGCCTCATAT
	CTCTGCATGATTTCCACTGGAACATGGAACCCTAAGGGCCCCGATCTTAGCAACTGTA
	CCTCACACTGGGTGAATCAGCTGGCTCAGAAGATCAGAAGCGGAGAAAATGCTGCTAG
	TCTTGCCAATGAACTGGCTAAACATACCAAAGGGCCAGTGTTTGCTGGGGATGTAAGT
	TCTTCAGTGAGATTGATGGAGCAGTTGGTGGACATCCTTGATGCACAGCTGCAGGAAC
	TGAAACCTAGTGAAAAAGATTCAGCTGGACGGAGTTATAACAAGCTCCAAAAACGAGA
	GAAGACATGCAGGGCTTACCTTAAGGCAATTGTTGACACAGTGGACAACCTTCTGAGA
	CCTGAAGCTTTGGAATCATGGAAACATATGAATTCTTCTGAACAAGCACATACTGCAA
	CAATGTTACTCGATACATTGGAAGAAGGAGCTTTTGTCCTAGCTGACAATCTTTTAGA
	ACCAACAAGGGTCTCAATGCCCACAGAAAATATTGTCCTGGAAGTTGCCGTACTCAGT
	ACAGAAGGACAGATCCAAGACTTTAAATTTCCTCTGGGCATCAAAGGAGCAGGCAGCT
	CAATCCAACTGTCCGCAAATACCGTCAAACAGAACAGCAGGAATGGGCTTGCAAAGTT
	GGTGTTCATCATTTACCGGAGCCTGGGACAGTTCCTTAGTACAGAAAATGCAACCATT
	AAACTGGGTGCTGATTTTATTGGTCGTAATAGCACCATTGCAGTGAACTCTCACGTCA
	TTTCAGTTTCAATCAATAAAGAGTCCAGCCGAGTATACCTGACTGATCCTGTGCTTTT
	TACCCTGCCACACATTGATCCTGACAATTATTTCAATGCAAACTGCTCCTTCTGGAAC
	TACTCAGAGAGAACTATGATGGGATATTGGTCTACCCAGGGCTGCAAGCTGGTTGACA
	CTAATAAAACTCGAACAACGTGTGCATGCAGCCACCTAACCAATTTTGCAATTCTCAT
	GGCCCACAGGGAAATTGCATATAAAGATGGCGTTCATGAATTACTTCTTACAGTCATC
	ACCTGGGTGGGAATTGTCATTTCCCTTGTTTGCCTGGCTATCTGCATCTTCACCTTCT
	GCTTTTTCCGTGGCCTACAGAGTGACCGAAATACTATTCACAAGAACCTTTGTATCAA
	CCTTTTCATTGCTGAATTTATTTTCCTAATAGGCATTGATAAGACAAAATATGCGATT
	GCATGCCCAATATTTGCAGGACTTCTACACTTTTTCTTTTTGGCAGCTTTTGCTTGGA
	TGTGCCTAGAAGGTGTGCAGCTCTACCTAATGTTAGTTGAAGTTTTTGAAAGTGAATA
	TTCAAGGAAAAAATATTACTATGTTGCTGGTTACTTGTTTCCTGCCACAGTGGTTGGA
	GTTTCAGCTGCTATTGACTATAAGAGCTATGGAACAGAAAAAGCTTGCTGGCTTCATG
	TTGATAACTACTTTATATGGAGCTTCATTGGACCTGTTACCTTCATTATTCTGCTAAA
	TATTATCTTCTTGGTGATCACATTGTGCAAAATGGTGAAGCATTCAAACACTTTGAAA
	CCAGATTCTAGCAGGTTGGAAAACATTAAGTCTTGGGTGCTTGGCGCTTTCGCTCTTC
	TGTGTCTTCTTGGCCTCACCTGGTCCTTTGGGTTGCTTTTTATTAATGAGGAGACTAT
	TGTGATGGCATATCTCTTCACTATATTTAATGCTTTCCAGGGAGTGTTCATTTTCATC
	TTTCACTGTGCTCTCCAAAAGAAAGTACGAAAAGAATATGGCAAGTGCTTCAGACACT
	CATACTGCTGTGGAGGCCTCCCAACTGAGAGTCCCCACAGTTCAGTGAAGGCATCAAC
	CACCAGAACCAGTGCTCGCTATTCCTCTGGCACACAGAGTCGTATAAGAAGAATGTGG
	AATGATACTGTGAGAAAACAATCAGAATCTTCTTTTATCTCAGGTGACATCAATAGCA
	CTTCAACACTTAATCAAGGAATGACTGGCAATTACCTACTAACAAACCCTCTTCTTCG
	ACCCCACGGCACTAACAACCCCTATAACACATTGCTCGCTGAAACAGTTGTATGTAAT
	GCCCCTTCAGCTCCTGTATTTAACTCACCAGGACATTCACTGAACAATGCCAGGGATA
	CAAGTGCCATGGATACTCTACCGCTAAATGGTAATTTTAACAACAGCTACTCGCTGCA
	CAAGGGTGACTATAATGACAGCGTGCAAGTTGTGGACTGTGGACTAAGTCTGAATGAT
	ACTGCTTTTGAGAAAATGATCATTTCAGAATTAGTGCACAACAACTTACGGGGCAGCA
	GCAAGACTCACAACCTCGAGCTCACGCTACCAGTCAAACCTGTGATTGGAGGTAGCAG
	CAGTGAAGATGATGCTATTGTGGCAGATGCTTCATCTTTAATGCACAGCGACAACCCA
	GGGCTGGAGCTCCATCACAAAGAACTCGAGGCACCACTTATTCCTCAGCGGACTCACT
	CCCTTCTGTACCAACCCCAGAAGAAAGTGAAGTCCGAGGGAACTGACAGCTATGTCTC
	CCAACTGACAGCAGAGGCTGAAGATCACCTACAGTCCCCCAACAGAGACTCTCTTTAT
	ACAAGCATGCCCAATCTTAGAGACTCTCCCTATCCGGAGAGCAGCCCTGACATGGAAG
	AAGACCTCTCTCCCTCCAGGAGGAGTGAGAATGAGGACATTTACTATAAAAGCATGCC
	AAATCTTGGAGCTGGCCATCAGCTTCAGATGTGCTACCAGATCAGCAGGGGCAATAGT
	GATGGTTATATAATCCCCATTAACAAAGAAGGGTGTATTCCAGAAGGAGATGTTAGAG
	AAGGACAAATGCAGCTGGTTACAAGTCTTTAATCATACAGCTAAGGAATTCCAAGGGC
	CACATGCGAGTATTAATAAATAAAGACACCA
	ORF Start: ATG at 61		ORF Stop: TAA at 4438
	SEQ ID NO:100	1459 aa	MW at 163347.0 Da
NOV22a,	MVSSGCRMRSLWFIIVISFLPNTEGFSRAALPFGLVRRELSCEGYSIDLRCPGSDVIM
CG118160-01	IESANYGRTDDKICDADPFQMENTDCYLPDAFKIMTQRCNNRTQCIVVTGSDVFPDPC
Protein Sequence	PGTYKYLEVQYECVPYIFVCPGTLKAIVDSPCIYEAEQKAGAWCKDPLQAADKIYFMP
	WTPYRTDTLIEYASLEDFQNSRQTTTYKLPNRVDGTGFVVYDGAVFFNKERTRNIVKF
	DLRTRIKSGEAIINYANYHDTSPYRWGGKTDIDLAVDENGLWVIYATEQNNGMIVISQ
	LNPYTLRFEATWETVYDKRAASNAFMICGVLYVVRSVYQDNESETGKNSIDYIYNTRL
	NRGEYVDVPFPNQYQYIAAVDYNPRDNQLYVWNNNFILRYSLEFGPPDPAQVPTTAVT
	ITSSAELFKTIISTTSTTSQKGPMSTTVAGSQEGSKGTKPPPAVSTTKIPPITNIFPL
	PERFCEALDSKGIKWPQTQRGMMVERPCPKGTRGTASYLCMISTGTWNPKGPDLSNCT
	SHWVNQLAQKIRSGENAASLANELAKHTKGPVFAGDVSSSVRLMEQLVDILDAQLQEL
	KPSEKDSAGRSYNKLQKREKTCRAYLKAIVDTVDNLLRPEALESWKHMNSSEQAHTAT
	MLLDTLEEGAFVLADNLLEPTRVSMPTENIVLEVAVLSTEGQIQDFKFPLGIKGAGSS
	IQLSANTVKQNSRNGLAKLVFIIYRSLGQFLSTENATIKLGADFIGRNSTIAVNSHVI
	SVSINKESSRVYLTDPVLFTLPHIDPDNYFNANCSFWNYSERTMMGYWSTQGCKLVDT
	NKTRTTCACSHLTNFAILMAHREIAYKDGVHELLLTVITWVGIVISLVCLAICIFTFC
	FFRGLQSDRNTIHKNLCINLFIAEFIFLIGIDKTKYAIACPIFAGLLHFFFLAAFAWM
	CLEGVQLYLMLVEVFESEYSRKKYYYVAGYLFPATVVGVSAAIDYKSYGTEKACWLHV
	DNYFIWSFIGPVTFIILLNIIFLVITLCKMVKHSNTLKPDSSRLENIKSWVLGAFALL
	CLLGLTWSFGLLFINEETIVMAYLFTIFNAFQGVFIFIFHCALQKKVRKEYGKCFRHS
	YCCGGLPTESPHSSVKASTTRTSARYSSGTQSRIRRMWNDTVRKQSESSFISGDINST
	STLNQGMTGNYLLTNPLLRPHGTNNPYNTLLAETVVCNAPSAPVFNSPGHSLNNARDT
	SAMDTLPLNGNFNNSYSLHKGDYNDSVQVVDCGLSLNDTAFEKMIISELVHNNLRGSS
	KTHNLELTLPVKPVIGGSSSEDDAIVADASSLMHSDNPGLELHHKELEAPLIPQRTHS
	LLYQPQKKVKSEGTDSYVSQLTAEAEDHLQSPNRDSLYTSMPNLRDSPYPESSPDMEE
	DLSPSRRSENEDIYYKSMPNLGAGHQLQMCYQISRGNSDGYIIPINKEGCIPEGDVRE
	GQMQLVTSL

[0432] Further analysis of the NOV22a protein yielded the following properties shown in Table 22B.

TABLE 22B
Protein Sequence Properties NOV22a
PSort     0.6400 probability located in plasma membrane; 0.4600
analysis: probability located in Golgi body; 0.3700 probability located
          in endoplasmic reticulum (membrane); 0.1000 probability
          located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 26 and 27
analysis:

[0433] A search of the NOV22a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 22C.

TABLE 22C
Geneseq Resulst for NOV22a
		NOV22a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU10540	Rat CIRL-2 variant BC (YSG2)	1 . . . 1459	1383/1478 (93%)	0.0
	polypeptide - Rattus sp, 1478 aa.	1 . . . 1478	1420/1478 (95%)
	[WO200175440-A2, 11 OCT. 2001]
AAB15725	Human lectomedin-1 gamma cDNA -	1 . . . 1459	1403/1459 (96%)	0.0
	Homo sapiens, 1403 aa.	1 . . . 1403	1403/1459 (96%)
	[WO200052039-A2, 08 SEP. 2000]
AAY41087	Human lectomedin-1 gamma	1 . . . 1459	1403/1459 (96%)	0.0
	polypeptide - Homo sapiens, 1403	1 . . . 1403	1403/1459 (96%)
	aa. [WO9945111-A1, 10 SEP. 1999]
AAU30676	Novel human secreted protein	1 . . . 1459	1382/1470 (94%)	0.0
	#1167 - Homo sapiens, 1425 aa.	12 . . . 1425	1386/1470 (94%)
	[WO200179449-A2, 25 OCT. 2001]
AAB15723	Human lectomedin-1 alpha - Homo	1 . . . 1172	1155/1172 (98%)	0.0
	sapiens, 1177 aa. [WO200052039-	1 . . . 1159	1157/1172 (98%)
	A2, 08 SEP. 2000]

[0434] In a BLAST search of public sequence datbases, the NOV22a protein was found to have homology to the proteins shown in the BLASTP data in Table 22D.

TABLE 22D
Public BLASTP Results for NOV22a
		NOV22a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O97815	Latrophilin 2 splice variant bbbaf -	1 . . . 1459	1436/1463 (98%)	0.0
	Bos taurus (Bovine), 1463 aa.	1 . . . 1463	1450/1463 (98%)
O97817	Latrophilin 2 splice variant bbbbf -	1 . . . 1459	1435/1478 (97%)	0.0
	Bos taurus (Bovine), 1478 aa.	1 . . . 1478	1449/1478 (97%)
O97811	Latrophilin 2 splice variant bbaaf -	1 . . . 1459	1423/1463 (97%)	0.0
	Bos taurus (Bovine), 1450 aa.	1 . . . 1450	1437/1463 (97%)
O97813	Latrophilin 2 splice variant bbabf -	1 . . . 1459	1422/1478 (96%)	0.0
	Bos taurus (Bovine), 1465 aa.	1 . . . 1465	1436/1478 (96%)
T17159	CL2AC protein - rat, 1463 aa.	1 . . . 1459	1384/1463 (94%)	0.0
		1 . . . 1463	1421/1463 (96%)

[0435] PFam analysis predicts that the NOV22a protein contains the domains shown in the Table 22E.

TABLE 22E
Domain Analysis of NOV22a
		Identities/
	NOV22a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
Gal_Lectin	49 . . . 129	37/93 (40%)	1.5e−44
		77/93 (83%)
OLF	138 . . . 394	122/293 (42%)	7.6e−142
		218/293 (74%)
HRM	466 . . . 526	21/79 (27%)	1.5e−15
		48/79 (61%)
GPS	784 . . . 836	27/55 (49%)	1.4e−27
		52/55 (95%)
7tm_2	844 . . . 1091	98/274 (36%)	2.3e−111
		227/274 (83%)
Latrophilin	1093 . . . 1459	291/394 (74%)	6.2e−302
		355/394 (90%)

Example 23

[0436] The NOV23 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 23A.

TABLE 23A
NOV23 Sequence Analysis
	SEQ ID NO:101	1809 bp
NOV23a,	CGGGAAGTAGGCGGGGTGACGTGTGGTTGACGAGCTCGGCGGCGGGTTTGCTGAGATC
CG119685-01 DNA	TGTGGCCGGCGGCAGCTGGTGCGGGGGGCAGCTGAGAGCGAGAGGTGGATCGGGGCGG
Sequence	TGTGTGGCCAGGGCCATGACGGGCAACGCCGGGGAGTGGTGCCTCATGGAAAGCGACC
	CCGGGGTCTTCACCGAGCTCATTAAAGGATTCGGTTGCCGAGGAGCCCAAGTAGAAGA
	AATATGGAGTTTAGAGCCTGAGAATTTTGAAAAATTAAAGCCAGTTCATGGGTTAATT
	TTTCTTTTCAAGTGGCAGCCAGGAGAAGAACCAGCAGGCTCTGTGGTTCAGGACTCCC
	GACTTGACACGATATTTTTTGCTAAGCAGGTAATTAATAATGCTTGTGCTACTCAAGC
	CATAGTGAGTGTGTTACTGAACTGTACCCACCAGGATGTCCATTTAGGCGAGACATTA
	TCAGAGTTTAAAGAATTTTCACAAAGTTTTGATGCAGCTATGAAAGGCTTGGCACTGA
	GCAATTCAGATGTGATTCGACAAGTACACAACAGTTTCGCCAGACAGCAAATGTTTGA
	ATTTGATACGAAGACATCAGCAAAAGAAGAAGATGCTTTTCACTTTGTCAGTTATGTT
	CCTGTTAATGGGAGACTGTATGAATTAGATGGATTAAGAGAAGGACCGATTGATTTAG
	GTGCATGCAATCAAGATGATTGGATCAGTGCAGTAAGGCCTGTCATAGAAAAAAGGAT
	ACAAAAAGACGGGTTTTCACCATGTTGCCCAGGCTGGTCTCAGACTCCTGAGCTCAAG
	CCATCCGCCTGCCTCGACCTCCCAAAGTGGTACAGTGAAGGTGAAATTCGATTTAATT
	TAATGGCCATTGTGTCTGACAGAAAAATGATATATGAGCAGAAGATAGCAGAGTTACA
	AAGACAACTTGCAGAGGAGGAACCCATGGATACAGATCAAGGTAATAGTATGTTAAGT
	GCTATTCAGTCAGAAGTTGCCAAAAATCAGATGCTTATTGAAGAAGAAGTACAGAAAT
	TAAAAAGATACAAGATTGAGAATATCAGAAGGAAGCATAATTATCTGCCTTTCATTAT
	GGAATTGTTAAAGACTTTAGCAGAACACCAGCAGTTAATACCACTAGTAGAAAAGGCA
	AAAGAAAAACAGAACGCAAAGAAAGCTCAGGAAACCAAATGAAGATGTTTTCAGATAT
	GTACACATTTCTGCTTCTGCACATATTTTCATGGAAACCATTATGTATAAAGAACTTA
	GAGCAACATCCTAATTGGCTCAGTGCACGTTTGGCAATAGTGCCAGCCTGTCTTGTCT
	TTAATGCATGGATTCATAAACTTCTTCCCTACCTGCATCATGTGCATGTAGTGCATAT
	TAAATGAAAGTGATATTAAGAATGCTTTCCCAAATTCCATTATTTGACATTGAGTCTG
	ACAACTGTTAGTTTTCTGGTTGTCCAACTACCATATGAAGCTAGAAAATGCACAAACG
	ATATTCCTTATCTGTAATTTAAATACTTAAAATTTGCAATTGTCAGATCTTGATTAAA
	CTGGTTGTCTTATTTCTTCTCATCATTAACGGAAAAAAAATCAGTATTTCTATCTTTG
	ATATCTAAGTGTTTTGAGGATTTTAAAACTGAATTTTATCTGCTATACCAGTTATTTG
	AGAAAGTATGATTTTAATGTAAATCATTTAAAAAGGACAAAAGTATAATTTCCAGTGA
	TTTTCACTGCTGTCAGTAGAAAAGTAATAAACATCTCAATTTTAAAAAAAAAAAAAAA
	AAAAAAAAAAA
	ORF Start: ATG at 132		ORF Stop: TGA at 1200
	SEQ ID NO:102	356 aa	MW at 40551.9 Da
NOV23a,	MTGNAGEWCLMESDPGVFTELIKGFGCRGAQVEEIWSLEPENFEKLKPVHGLIFLFKW
CG119685-01	QPGEEPAGSVVQDSRLDTIFFAKQVINNACATQAIVSVLLNCTHQDVHLGETLSEFKE
Protein Sequence	FSQSFDAAMKGLALSNSDVIRQVHNSFARQQMFEFDTKTSAKEEDAFHFVSYVPVNGR
	LYELDGLREGPIDLGACNQDDWISAVRPVIEKRIQKDGFSPCCPGWSQTPELKPSACL
	DLPKWYSEGEIRFNLMAIVSDRKMIYEQKIAELQRQLAEEEPMDTDQGNSMLSAIQSE
	VAKNQMLIEEEVQKLKRYKIENIRRKHNYLPFIMELLKTLAEHQQLIPLVEKAKEKQN
	AKKAQETK

[0437] Further analysis of the NOV23a protein yielded the following properties shown in Table 23B.

TABLE 23B
Protein Sequence Properties NOV23a
PSort     0.3000 probability located in microbody (peroxisome); 0.3000
analysis: probability located in nucleus; 0.1000 probability located in
          mitochondrial matrix space; 0.1000 probability located in
          lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0438] A search of the NOV23a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 23C.

TABLE 23C
Geneseq Results for NOV21a
		NOV23a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM79425	Human protein SEQ ID NO 3071 -	1 . . . 356	329/356 (92%)	0.0
	Homo sapiens, 395 aa.	67 . . . 395	329/356 (92%)
	[WO200157190-A2, 09 AUG. 2001]
AAM78441	Human protein SEQ ID NO 1103 -	1 . . . 356	329/356 (92%)	0.0
	Homo sapiens, 329 aa.	1 . . . 329	329/356 (92%)
	[WO200157190-A2, 09 AUG. 2001]
AAB74674	Human protease and protease	1 . . . 356	328/356 (92%)	0.0
	inhibitor PPIM-7 - Homo sapiens,	68 . . . 396	328/356 (92%)
	396 aa. [WO200110903-A2, 15 FEB. 2001]
AAU23500	Novel human enzyme polypeptide	1 . . . 344	314/344 (91%)	e−176
	#586 - Homo sapiens, 388 aa.	73 . . . 388	314/344 (91%)
	[WO200155301-A2, 02 AUG. 2001]
AAB56931	Human prostate cancer antigen	1 . . . 344	313/344 (90%)	e−175
	protein sequence SEQ ID NO: 1509 -	73 . . . 388	313/344 (90%)
	Homo sapiens, 388 aa.
	[WO200055174-A1, 21 SEP. 2000]

[0439] In a BLAST search of public sequence datbases, the NOV23a protein was found to have homology to the proteins shown in the BLASTP data in Table 23D.

TABLE 23D
Public BLASTP Results for NOV23a
		NOV23a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9Y5K5	Ubiquitin carboxyl-terminal hydrolase	1 . . . 356	328/356 (92%)	0.0
	isozyme L5 (EC 3.4.19.12) (UCH- L5)	1 . . . 329	328/356 (92%)
	(Ubiquitin thiolesterase L5) (Ubiquitin
	C-terminal hydrolase UCH37) (CGI-
	70) (AD-019) - Homo sapiens
	(Human), 329 aa.
Q96BJ9	Hypothetical 37.5 kDa protein - Homo	1 . . . 356	328/356 (92%)	0.0
	sapiens (Human), 328 aa.	1 . . . 328	328/356 (92%)
Q9XSJ0	Ubiquitin carboxyl-terminal hydrolase	1 . . . 356	324/356 (91%)	0.0
	isozyme L5 (EC 3.4.19.12) (UCH- L5)	1 . . . 328	327/356 (91%)
	(Ubiquitin thiolesterase L5) (Ubiquitin
	C-terminal hydrolase UCH37) - Bos
	taurus (Bovine), 328 aa.
Q9WUP7	Ubiquitin carboxyl-terminal hydrolase	1 . . . 356	319/356 (89%)	e−180
	isozyme L5 (EC 3.4.19.12) (UCH- L5)	1 . . . 329	327/356 (91%)
	(Ubiquitin thiolesterase L5) (Ubiquitin
	C-terminal hydrolase UCH37) - Mus
	musculus (Mouse), 329 aa.
AAH06891	Unknown (protein for MGC: 6295) -	1 . . . 356	318/356 (89%)	e−178
	Mus musculus (Mouse), 328 aa.	1 . . . 328	326/356 (91%)

[0440] PFam analysis predicts that the NOV23a protein contains the domains shown in the Table 23E.

TABLE 23E
Domain Analysis of NOV23a
		Identities/
	NOV23a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
UCH	7 . . . 213	60/233 (26%)	6.9e−11
		116/233 (50%)

Example 24

[0441] The NOV24 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 24A.

TABLE 24A
NOV24 Sequence Analysis
	SEQ ID NO:103	3499 bp
NOV24a,	GAATAACGGAAGGGAGAATATGACAGATACCTAGCATCTAGCAAAATAATGGCAGCTG
CG120443-01 DNA	CTTACCTTGACCCCAACTTGAATCACACACCAAATTCGAGTACTAAGACTCACCTGGG
Sequence	TACTGGTATGGAACGTTCTCCTGGTGCAATGGAGCGAGTATTAAAGGTCTTTCATTAT
	TTTGAAAGCAATAGTGAGCCAACCACCTGGGCCAGTATTATCAGGCATGGAGATGCTA
	CTGATGTCAGGGGCATCATTCAGAAGATAGTGGACAGTCACAAAGTAAAGCATGTGGC
	CTGCTATGGATTCCGCCTCAGTCACCTGCGGTCAGAGGAGGTTCACTGCCTTCACGTG
	GATATGGGCGTCTCCAGTGTGAGGGAGAAGTATGAGCTTGCTCACCCACCAGAGGAGT
	GGAAATATGAATTGAGAATTCGTTATTTGCCAAAAGGATTTCTAAACCAGTTTACTGA
	AGATAAGCCAACTTTGAATTTCTTCTATCAACAGGTGAAGAGCGATTATATGTTAGAG
	ATAGCTGATCAAGTGGACCAGGAAATTGCTTTGAAGTTGGGTTGTCTAGAAATACGGC
	GATCATACTGGGAGATGCGGGGCAATGCACTAGAAAAGAAGTCTAACTATGAAGTATT
	AGAAAAAGATGTTGGTTTAAAGCGATTTTTTCCTAAGAGTTTACTGGATTCTGTCAAG
	GCCAAAACACTAAGAAAACTGATCCAACAAACATTTAGACAATTTGCCAACCTTAATA
	GAGAAGAAAGTATTCTGAAATTCTTTGAGATCCTGTCTCCAGTCTACAGATTTGATAA
	GGAATGCTTCAAGTGTGCTCTTGGTTCAAGCTGGATTATTTCAGTGGAACTGGCAATC
	GGCCCAGAAGAAGGAATCAGTTACCTAACGGACAAGGGCTGCAATCCTCTGACAGTGA
	CGGCACCATCCCTAACCATTGCGGAGAATATGGCTGACCTAATAGATGGGTACTGCCG
	GCTGGTGAATGGAACCTCGCAGTCATTTATCATCAGACCTCAGAAAGAAGGTGAACGG
	GCTTTGCCATCAATACCAAAGTTGGCCAACAGCGAAAAGCAAGGCATGCGGACACACG
	CCGTCTCTGTGTCAGAAACAGATGATTATGCTGAGATTATAGATGAAGAAGATACTTA
	CACCATGCCCTCAACCAGGGATTATGAGATTCAAAGAGAAAGAATAGAACTTGGACGA
	TGTATTGGAGAAGGCCAATTTGGAGATGTACATCAAGGCATTTATATGAGTCCAGAGA
	ATCCAGCTTTGGCGGTTGCAATTAAAACATGTAAAAACTGTACTTCGGACAGCGTGAG
	AGAGAAATTTCTTCAAGAAGCCTTAACAATGCGTCAGTTTGACCATCCTCATATTGTG
	AAGCTGATTGGAGTCATCACAGAGAATCCTGTCTGGATAATCATGGAGCTGTGCACAC
	TTGGAGAGCTGAGGTCATTTTTGCAAGTAAGGAAATACAGTTTGGATCTAGCATCTTT
	GATCCTGTATGCCTATCAGCTTAGTACAGCTCTTGCATATCTAGAGAGCAAAAGATTT
	GTACACAGGGACATTGCTGCTCGGAATGTTCTGGTGTCCTCAAATGATTGTGTAAAAT
	TAGGAGACTTTGGATTATCCCGATATATGGAAGATAGTACTTACTACAAAGCTTCCAA
	AGGAAAATTGCCTATTAAATGGATGGCTCCAGAGTCAATCAATTTTCGACGTTTTACC
	TCAGCTAGTGACGTATGGATGTTTGGTGTGTGTATGTGGGAGATACTGATGCATGGTG
	TGAAGCCTTTTCAAGGAGTGAAGAACAATGATGTAATCGGTCGAATTGAAAATGGGGA
	AAGATTACCAATGCCTCCAAATTGTCCTCCTACCCTCTACAGCCTTATGACGAAATGC
	TGGGCCTATGACCCCAGCAGGCGGCCCAGGTTTACTGAACTTAAAGCTCAGCTCAGCA
	CAATCCTGGAGGAAGAGAAGGCTCAGCAAGAAGAGCGCATGAGGATGGAGTCCAGAAG
	ACAGGCCACAGTGTCCTGGGACTCCGGAGGGTCTGATGAAGCACCGCCCAAGCCCAGC
	AGACCGGGTTATCCCAGTCCGAGGTCCAGCGAAGGATTTTATCCCAGCCCACAGCACA
	TGGTACAAACCAATCATTACCAGGTTTCTGGCTACCCTGGTTCACATGGAATCACAGC
	CATGGCTGGCAGCATCTATCCAGGTCAGGCATCTCTTTTGGACCAAACAGATTCATGG
	AATCATAGACCTCAGGAGATAGCAATGTGGCAGCCCAATGTGGAGGACTCTACAGTAT
	TGGACCTGCGAGGGATTGGGCAAGTGTTGCCAACCCATCTGATGGAAGAGCGTCTAAT
	CCGACAGCAACAGGAAATGGAAGAAGATCAGCGCTGGCTGGAAAAAGAGGAAAGATTT
	CTGAAACCTGATGTGAGACTCTCTCGAGGCAGTATTGACAGGGAGGATGGAAGTCTTC
	AGGGTCCGATTGGAAACCAACATATATATCAGCCTGTGGGTAAACCAGATCCTGCAGC
	TCCACCAAAGAAACCGCCTCGCCCTGGAGCTCCCGGTCATCTGGGAAGCCTTGCCAGC
	CTCAGCAGCCCTGCTGACAGCTACAACGAGGGTGTCAAGCTTCAGCCCCAGGAAATCA
	GCCCCCCTCCTACTGCCAACCTGGACCGGTCGAATGATAAGGTGTACGAGAATGTGAC
	GGGCCTGGTGAAAGCTGTCATCGAGATGTCCAGTAAAATCCAGCCAGCCCCACCAGAG
	GAGTATGTCCCTATGGTGAAGGAAGTCGGCTTGGCCCTGAGGACATTATTGGCCACTG
	TGGATGAGACCATTCCCCTCCTACCAGCCAGCACCCACCGAGAGATTGAGATGGCACA
	GAAGCTATTGAACTCTGACCTGGGTGAGCTCATCAACAAGATGAAACTGGCCCAGCAG
	TATGTCATGACCAGCCTCCAGCAAGAGTACAAAAAGCAAATGCTGACTGCTGCTCACG
	CCCTGGCTGTGGATGCCAAAAACTTACTCGATGTCATTGACCAAGCAAGACTGAAAAT
	GCTTGGGCAGACGAGACCACACTGAGCCTCCCCTAGGAGCACGTCTTGCTACCCTCTT
	TTGAAGATGTTCTCTAGCCTTCCACCAGCAGCGAGGAATTAACCCTGTGTCCTCAGTC
	GCCAGCACTTACAGCTCCAACTTTTTTGAATGACCATCTGGTTGAAAAATCTTTCTCA
	TATAAGTTTAACCACACTTTGATTTGGGTTCATTTTTTGTTTTGTTTTTTTCAATCAT
	GATATTCAGAAAAATCCAGGATCCAAAATGTGGCGTTTTTCTAAGAATGAAAATTATA
	TGTAAGCTTTTAAGCATCATGAAGAACAATTTATGTTCACATTAAGATACGTTCTAAA
	GGGGGATGGCCAAGGGGTGACATCTTAATTCCTAAACTACCTTAGCTGCATAGTGGAA
	GAGGAGAGCTAGAAGCAAA
	ORF Start: ATG at 49		ORF Stop: TGA at 3097
	SEQ ID NO:104	1016 aa	MW at 115218.3 Da
NOV24a,	MAAAYLDPNLNHTPNSSTKTHLGTGMERSPGAMERVLKVFHYFESNSEPTTWASIIRH
CG120443-01	GDATDVRGIIQKIVDSHKVKHVACYGFRLSHLRSEEVHWLHVDMGVSSVREKYELAHP
Protein Sequence	PEEWKYELRIRYLPKGFLNQFTEDKPTLNFFYQQVKSDYMLEIADQVDQEIALKLGCL
	EIRRSYWEMRGNALEKKSNYEVLEKDVGLKRFFPKSLLDSVKAKTLRKLIQQTFRQFA
	NLNREESILKFFEILSPVYRFDKECFKCALGSSWIISVELAIGPEEGISYLTDKGCNP
	LTVTAPSLTIAENMADLIDGYCRLVNGTSQSFIIRPQKEGERALPSIPKLANSEKQGM
	RTHAVSVSETDDYAEIIDEEDTYTMPSTRDYEIQRERIELGRCIGEGQFGDVHQGIYM
	SPENPALAVAIKTCKNCTSDSVREKFLQEALTMRQFDHPHIVKLIGVITENPVWIIME
	LCTLGELRSFLQVRKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSND
	CVKLGDFGLSRYMEDSTYYKASKGKLPIKWMAPESINFRRFTSASDVWMFGVCMWEIL
	MHGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLYSLMTKCWAYDPSRRPRFTELKA
	QLSTILEEEKAQQEERMRMESRRQATVSWDSGGSDEAPPKPSRPGYPSPRSSEGFYPS
	PQHMVQTNHYQVSGYPGSHGITAMAGSIYPGQASLLDQTDSWNHRPQEIAMWQPNVED
	STVLDLRGIGQVLPTHLMEERLIRQQQEMEEDQRWLEKEERFLKPDVRLSRGSIDRED
	GSLQGPIGNQHIYQPVGKPDPAAPPKKPPRPGAPGHLGSLASLSSPADSYNEGVKLQP
	QEISPPPTANLDRSNDKVYENVTGLVKAVIEMSSKIQPAPPEEYVPMVKEVGLALRTL
	LATVDETIPLLPASTHREIEMAQKLLNSDLGELINKMKLAQQYVMTSLQQEYKKQMLT
	AAHALAVDAKNLLDVIDQARLKMLGQTRPH
	SEQ ID NO:105	3383 bp
NOV24b,	GAATAACGGAAGGGAGAATATGACAGATACCTAGCATCTAGCAAAATAATGGCAGCTG
CG120443-02 DNA	CTTACCTTGACCCCAACTTGAATCACACACCAAATTCGAGTACTAAGACTCACCTGGG
Sequence	TACTGGTATGGAACGTTCTCCTGGTGCAATGGAGCGAGTATTAAAGGTCTTTCATTAT
	TTTGAAAGCAATAGTGAGCCAACCACCTGGGCCAGTATTATCAGGCATGGAGATGCTA
	CTGATGTCAGGGGCATCATTCAGAAGATAGTGGACAGTCACAAAGTAAAGCATGTGGC
	CTGCTATGGATTCCGCCTCAGTCACCTGCGGTCAGAGGAGGTTCACTGGCTTCACGTG
	GATATGGGCGTCTCCAGTGTGAGGGAGAAGTATGAGCTTGCTCACCCACCAGAGGAGT
	GGAAATATGAATTGAGAATTCGTTATTTGCCAAAAGGATTTCTAAACCAGTTTACTGA
	AGATAAGCCAACTTTGAATTTCTTCTATCAACAGGTGAAGAGCGATTATATGTTAGAG
	ATAGCTGATCAAGTGGACCAGGAAATTGCTTTGAAGTTGGGTTGTCTAGAAATACGGC
	GATCATACTGGGAGATGCGGGGCAATGCACTAGAAAAGAAGTCTAACTATGAAGTATT
	AGAAAAAGATGTTGGTTTAAAGCGATTTTTTCCTAAGAGTTTACTGGATTCTGTCAAG
	GCCAAAACACTAAGAAAACTGATCCAACAAACATTTAGACAATTTGCCAACCTTAATA
	GAGAAGAAAGTATTCTGAAATTCTTTGAGATCCTGTCTCCAGTCTACAGATTTGATAA
	GGAATGCTTCAAGTGTGCTCTTGGTTCAAGCTGGATTATTTCAGTGGAACTGGCAATC
	GGCCCAGAAGAAGGAATCAGTTACCTAACGGACAAGGGCTGCAATCCTCTGACAGTGA
	CGGCACCATCCCTAACCATTGCGGAGAATATGGCTGACCTAATAGATGGGTACTGCCG
	GCTGGTGAATGGAACCTCGCAGTCATTTATCATCAGACCTCAGAAAGAAGGTGAACGG
	GCTTTGCCATCAATACCAAAGTTGGCCAACAGCGAAAAGCAAGGCATGCGGACACACG
	CCGTCTCTGTGTCAGAAACAGATGATTATGCTGAGATTATAGATGAAGAAGATACTTA
	CACCATGCCCTCAACCAGGGATTATGAGATTCAAAGAGAAAGAATAGAACTTGGACGA
	TGTATTGGAGAAGGCCAATTTGGAGATGTACATCAAGGCATTTATATGAGTCCAGAGA
	ATCCAGCTTTGGCGGTTGCAATTAAAACATGTAAAAACTGTACTTCGGACAGCGTGAG
	AGAGAAATTTCTTCAAGAAGCCTTAACAATGCGTCAGTTTGACCATCCTCATATTGTG
	AAGCTGATTGGAGTCATCACAGAGAATCCTGTCTGGATAATCATGGAGCTGTGCACAC
	TTGGAGAGGGACATTGCTGCTCGGAATGTTCTGGTGTCCTCAAATGATTGTGTAAAAT
	TAGGAGACTTTGGATTATCCCGATATATGGAAGATAGTACTTACTACAAAGCTTCCAA
	AGGAAAATTGCCTATTAAATGGATGGCTCCAGAGTCAATCAATTTTCGACGTTTTACC
	TCAGCTAGTGACGTATGGATGTTTGGTGTGTGTATGTGGGAGATACTGATGCATGGTG
	TGAAGCCTTTTCAAGGAGTGAAGAACAATGATGTAATCGGTCGAATTGAAAATGGGGA
	AAGATTACCAATGCCTCCAAATTGTCCTCCTACCCTCTACAGCCTTATGACGAAATGC
	TGGGCCTATGACCCCAGCAGGCGGCCCAGGTTTACTGAACTTAAAGCTCAGCTCAGCA
	CAATCCTGGAGGAAGAGAAGGCTCAGCAAGAAGAGCGCATGAGGATGGAGTCCAGAAG
	ACAGGCCACAGTGTCCTGGGACTCCGGAGGGTCTGATGAAGCACCGCCCAAGCCCAGC
	AGACCGGGTTATCCCAGTCCGAGGTCCAGCGAAGGATTTTATCCCAGCCCACAGCACA
	TGGTACAAACCAATCATTACCAGGTTTCTGGCTACCCTGGTTCACATGGAATCACAGC
	CATGGCTGGCAGCATCTATCCAGGTCAGGCATCTCTTTTGGACCAAACAGATTCATGG
	AATCATAGACCTCAGGAGATAGCAATGTGGCAGCCCAATGTGGAGGACTCTACAGTAT
	TGGACCTGCGAGGGATTGGGCAAGTGTTGCCAACCCATCTGATGGAAGAGCGTCTAAT
	CCGACAGCAACAGGAAATGGAAGAAGATCAGCGCTGGCTGGAAAAAGAGGAAAGATTT
	CTGAAACCTGATGTGAGACTCTCTCGAGGCAGTATTGACAGGGAGGATGGAAGTCTTC
	AGGGTCCGATTGGAAACCAACATATATATCAGCCTGTGGGTAAACCAGATCCTGCAGC
	TCCACCAAAGAAACCGCCTCGCCCTGGAGCTCCCGGTCATCTGGGAAGCCTTGCCAGC
	CTCAGCAGCCCTGCTGACAGCTACAACGAGGGTGTCAAGCTTCAGCCCCAGGAAATCA
	GCCCCCCTCCTACTGCCAACCTGGACCGGTCGAATGATAAGGTGTACGAGAATGTGAC
	GGGCCTGGTGAAAGCTGTCATCGAGATGTCCAGTAAAATCCAGCCAGCCCCACCAGAG
	GAGTATGTCCCTATGGTGAAGGAAGTCGGCTTGGCCCTGAGGACATTATTGGCCACTG
	TGGATGAGACCATTCCCCTCCTACCAGCCAGCACCCACCGAGAGATTGAGATGGCACA
	GAAGCTATTGAACTCTGACCTGGGTGAGCTCATCAACAAGATGAAACTGGCCCAGCAG
	TATGTCATGACCAGCCTCCAGCAAGAGTACAAAAAGCAAATGCTGACTGCTGCTCACG
	CCCTGGCTGTGGATGCCAAAAACTTACTCGATGTCATTGACCAAGCAAGACTGAAAAT
	GCTTGGGCAGACGAGACCACACTGAGCCTCCCCTAGGAGCACGTCTTGCTACCCTCTT
	TTGAAGATGTTCTCTAGCCTTCCACCAGCAGCGAGGAATTAACCCTGTGTCCTCAGTC
	GCCAGCACTTACAGCTCCAACTTTTTTGAATGACCATCTGGTTGAAAAATCTTTCTCA
	TATAAGTTTAACCACACTTTGATTTGGGTTCATTTTTTGTTTTGTTTTTTTCAATCAT
	GATATTCAGAAAAATCCAGGATCCAAAATGTGGCGTTTTTCTAAGAATGAAAATTATA
	TGTAAGCTTTTAAGCATCATGAAGAACAATTTATGTTCACATTAAGATACGTTCTAAA
	GGGGGATGGCCAAGGGGTGACATCTTAATTCCTAAACTACCTTAGCTGCATAGTGGAA
	GAGGAGAGCTAGAAGCAAA
	ORF Start: ATG at 49		ORF Stop: TGA at 1495
	SEQ ID NO:106	482 aa	MW at 54980.2 Da
NOV24b,	MAAAYLDPNLNHTPNSSTKTHLGTGMERSPGAMERVLKVFHYFESNSEPTTWASIIRH
CG120443-02	GDATDVRGIIQKIVDSHKVKHVACYGFRLSHLRSEEVHWLHVDMGVSSVREKYELAHP
Protein Sequence	PEEWKYELRIRYLPKGFLNQFTEDKPTLNFFYQQVKSDYMLEIADQVDQEIALKLGCL
	EIRRSYWEMRGNALEKKSNYEVLEKDVGLKRFFPKSLLDSVKAKTLRKLIQQTFRQFA
	NLNREESILKFFEILSPVYRFDKECFKCALGSSWIISVELAIGPEEGISYLTDKGCNP
	LTVTAPSLTIAENMADLIDGYCRLVNGTSQSFIIRPQKEGERALPSIPKLANSEKQGM
	RTHAVSVSETDDYAEIIDEEDTYTMPSTRDYEIQRERIELGRCIGEGQFGDVHQGIYM
	SPENPALAVAIKTCKNCTSDSVREKFLQEALTMRQFDHPHIVKLIGVITENPVWIIME
	LCTLGEGHCCSECSGVLK

[0442] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 24B.

TABLE 24B
Comparison of NOV24a against NOV24b.
Protein	NOV24a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV24b	1 . . . 470	470/470 (100%)
	1 . . . 470	470/470 (100%)

[0443] Further analysis of the NOV24a protein yielded the following properties shown in Table 24C.

TABLE 24C
Protein Sequence Properties NOV24a
PSort     0.3000 probability located in microbody (peroxisome); 0.3000
analysis: probability located in nucleus; 0.1000 probability located in
          mitochondrial matrix space; 0.1000 probability located in
          lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0444] A search of the NOV24a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 24D.

TABLE 24D
Geneseq Results for NOV24a
		NOV24a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB30327	Human focal adhesion kinase -	1 . . . 1016	1016/1052 (96%)	0.0
	Homo sapiens, 1052 aa.	1 . . . 1052	1016/1052 (96%)
	[U.S. Pat. No. 6133031-A, 17 OCT. 2000]
AAR88576	Human focal adhesion kinase -	1 . . . 1016	1013/1052 (96%)	0.0
	Homo sapiens, 1052 aa.	1 . . . 1052	1015/1052 (96%)
	[WO9602560-A1, 01 FEB. 1996]
AAR88577	Mouse focal adhesion kinase - Mus	1 . . . 1016	988/1052 (93%)	0.0
	musculus, 1052 aa. [WO9602560-	1 . . . 1052	1003/1052 (94%)
	A1, 01 FEB. 1996]
AAR88578	Chicken focal adhesion kinase -	1 . . . 1016	962/1054 (91%)	0.0
	Gallus domesticus, 1053 aa.	1 . . . 1053	993/1054 (93%)
	[WO9602560-A1, 01 FEB. 1996]
AAY06245	Human FAK-related non-kinase	657 . . . 1016	360/360 (100%)	0.0
	FRNK - Homo sapiens, 360 aa.	1 . . . 360	360/360 (100%)
	[WO9928750-A1, 10 JUN. 1999]

[0445] In a BLAST search of public sequence datbases, the NOV24a protein was found to have homology to the proteins shown in the BLASTP data in Table 24E.

TABLE 24E
Public BLASTP Results for NOV24a
		NOV24a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q05397	Focal adhesion kinase 1 (EC	1 . . . 1016	1016/1052 (96%)	0.0
	2.7.1.112) (FADK 1) (pp125FAK)	1 . . . 1052	1016/1052 (96%)
	(Protein- tyrosine kinase 2) - Homo
	sapiens (Human), 1052 aa.
P34152	Focal adhesion kinase 1 (EC	1 . . . 1016	988/1052 (93%)	0.0
	2.7.1.112) (FADK 1) (pp125FAK) -	1 . . . 1052	1003/1052 (94%)
	Mus musculus (Mouse), 1052 aa.
O35346	Focal adhesion kinase 1 (EC	1 . . . 1016	985/1055 (93%)	0.0
	2.7.1.112) (FADK 1) (pp125FAK) -	1 . . . 1055	1005/1055 (94%)
	Rattus norvegicus (Rat), 1055 aa.
JC5494	protein-tyrosine kinase (EC	1 . . . 1016	983/1055 (93%)	0.0
	2.7.1.112) - rat, 1081 aa.	27 . . . 1081	1003/1055 (94%)
A45388	protein-tyrosine kinase (EC	26 . . . 1016	939/1029 (91%)	0.0
	2.7.1.112) - chicken, 1028 aa.	1 . . . 1028	969/1029 (93%)

[0446] PFam analysis predicts that the NOV24a protein contains the domains shown in the Table 24F.

TABLE 24F
Domain Analysis of NOV24a
		Identities/
	NOV24a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
pkinase	386 . . . 640	82/292 (28%)	2.8e−73
		201/292 (69%)

Example 25

[0447] The NOV25 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 25A.

TABLE 25A
NOV25 Sequence Analysis
	SEQ ID NO:107	3459 bp
NOV25a,	TGCTTCCGCTCCCGGAGCGCGTGCGCCCTCTTACTCGGCTCCCCTTGGTTTCCTGGGG
CG120563-01 DNA	TCCTGCCCCTTCAAGCTGGGGCGGGAGTGGAGGACCCCGCTCTCAGGGGTTGCCGGAC
Sequence	CATGCGTTGGGGGCTGCGCCCTCGCGGGCCGGGCGCGGCCGCCCTGGCCACTGCCCGA
	AGTTTGTGGGGGACGCCCCGCCTTCCCTGCAGCCCGGGATGGCAAGGGGCGACGAAGA
	GGCTTCTGGTGCGGTCGGTCTCCGGGGCCAGTAACCACCAGCCGAACTCGAATAGTGG
	CAGATACCGGGACACGGTGCTGCTGCCGCAGACGAGCTTCCCCATGAAGCTGCTGGGC
	CGCCAGCAGCCGGACACGGAGCTGGAGATCCAGCAGAAATGTGGATTTTCAGAACTTT
	ATTCATGGCAAAGAGAAAGAAAAGTAAAGACAGAATTTTGCCTTCATGATGGACCTCC
	TTATGCAAACGGTGACCCTCATGTTGGACATGCTTTAAATAAGATTTTGAAAGACATA
	GCCAATCGATTCCATATGATGAATGGCTCCAAAATACATTTTGTGCCCGGCTGGGATT
	GTCATGGGTTGCCCATTGAAATAAAAGTATTATCAGAACTTGGTAGAGAAGCTCAGAA
	TCTTTCAGCTATGGAAATTAGAAAGAAAGCTAGATCATTTGCTAAAGCAGCCATTGAG
	AAACAGAAATCAGCATTTATTCGTTGGGGAATAATGGCAGATTGGAATAATTGCTACT
	ATACATTTGATGGGAAGTATGAAGCCAAACAGTTGAGAACTTTTTACCAAATGTATGA
	TAAGGGCTTGGTTTATCGATCTTACAAACCTGTGTTTTGGTCTCCGTCATCTAGGACT
	GCATTGGCTGAAGCAGAACTTGAATATAATCCTGAGCATGTCAGTCGTTCAATATATG
	TAAAATTTCCTCTCTTAAAGCCTTCTCCAAAATTGGCATCTCTTATAGATGGTTCATC
	TCCTGTTAGTATTTTGGTCTGGACCACACAACCTTGGACGATTCCAGCCAATGAAGCT
	GTTTGCTATATGCCTGAATCAAAGTATGCTGTTGTGAAATGTTCTAAGTCTGGAGACC
	TCTACGTACTGGCGGCAGATAAAGTAGCATCTGTTGCTTCTACTTTGGAAACAACATT
	TGAGACTATTTCAACACTTTCAGGTGTAGATTTGGAAAATGGTACTTGCAGTCATCCA
	TTAATTCCTGATAAAGCCTCTCCTCTTTTACCTGCAAATCATGTGACCATGGCAAAAG
	GAACGGGATTGGTTCACACAGCCCCAGCTCATGGTATGGAAGACTACGGTGTAGCGTC
	TCAGCACAACCTGCCCATGGATTGTCTAGTGGACGAAGATGGAGTTTTCACAGATGTT
	GCAGGTCCTGAACTTCAAAACAAGGCTGTCCTTGAAGAGGGAACTGATGTGGTTATAA
	AGATGCTTCAGACTGCAAAGAATTTGTTGAAAGAGGAGAAATTGGTGCATAGCTATCC
	GTATGACTGGAGGACCAAGAAACCTGTGGTTATTCGTGCCAGCAAGCAGTGGTTTATA
	AACATCACGGATATTAAGACTGCAGCCAAGGAATTGTTAAAAAAGGTGAAATTTATTC
	CTGGATCAGCACTGAATGGCATGGTTGAAATGATGGACAGGCGGCCATATTGGTGTAT
	ATCAAGGCAAAGAGTTTGGGGTGTTCCAATTCCTGTGTTTCATCATAAGACCAAGGAT
	GAATACTTGATCAACAGCCAAACCACTGAGCATATTGTTAAACTAGTGGAACAACACG
	GCAGTGATATCTGGTGGACTCTTCCCCCTGAACAACTTCTTCCAAAAGAAGTCTTATC
	TGAGGTTGGTGGCCCTGATGCCTTGGAATATGTGCCAGGTCAGGATATTTTGGACATC
	TGGTTTGATAGCGGAACTTCATGGTCTTATGTTCTTCCAGGTCCTGACCAAAGAGCAG
	ATTTGTATTTGGAAGGAAAAGACCAGCTCGGGGGTTGGTTTCAGTCATCCTTATTAAC
	AAGTGTGGCAGCAAGGAAGAGAGCACCTTATAAGACAGTGATTGTTCATGGATTTACC
	CTTGGAGAAAAGGGAGAAAAGATGTCCAAGTCTCTTGGGAATGTCATTCATCCTGATG
	TTGTCGTTAATGGAGGACAAGATCAAAGCAAAGAGCCTCCGTATGGTGCTGATGTCCT
	TCGCTGGTGGGTAGCTGATTCCAATGTCTTCACCGAAGTTGCAATTGGCCCATCCGTG
	CTCAATGCTGCCAGAGATGATATTAGCAAGCTTAGGAATACACTTCGCTTTCTTTTGG
	GAAATGTGGCTGATTTCAACCCAGAAACAGATTCCATCCCTGTAAACGATATGTATGT
	CATAGACCAGTACATGCTACACTTACTGCAGGATTTGGCAAACAAGATTACCGAATTA
	TACAAACAATATGATTTTGGAAAAGTTGTTCGGCTGTTACGGACGTTTTATACCAGAG
	AGCTCTCTAACTTTTATTTCAGTATAATCAAAGATAGGCTCTATTGTGAAAAGGAAAA
	TGACCCCAAACGACGCTCTTGTCAGACTGCATTAGTTGAAATTTTGGATGTAATAGTT
	CGTTCTTTTGCTCCCATTCTTCCTCACCTGGCTGAAGAGGTGTTCCAGCACATACCTT
	ATATTAAAGAGCCCAAGAGTGTTTTCCGTACTGGGTGGATTAGTACTAGTTCTATCTG
	GAAAAAGCCCGGGTTGGAAGAAGCTGTGGAGAGTGCGTGTGCAATGCGAGACTCATTT
	CTTGGAAGCATCCCTGGCAAAAATGCAGCTGAGTACAAGGTTATCACTGTGATAGAAC
	CTGGACTGCTTTTTGAGATAATAGAGATGCTGCAGTCTGAAGAGACTTCCAGCACCTC
	TCAGTTGAATGAATTAATGATGGCTTCTGAGTCAACTTTACTGGCTCAGGAACCACGA
	GAGATGACTGCAGATGTAATCGAGCTTAAAGGGAAATTCCTCATCAACTTAGAAGGTG
	GTGATATTCGTGAAGAGTCTTCCTATAAAGTAATTGTCATGCCGACTACGAAAGAAAA
	ATGCCCCCGTTGTTGGAAGTATACAGCGGAGTCTTCAGATACACTGTGTCCTCGATGT
	GCAGAAGTTGTCAGTGGAAAATAGTATTAACAGCTCACTCGAGCAAGAACCCTCCTGA
	CAGTACTGGCTGGAAGTTTGGATGGATTATTTACAATATAGGAAAGAAAGCCAAGATT
	TAGGTAATGAGTGGATGAGTAAATGGTGGAGGATGGGAGTCAAAATCAGAATTATAGA
	AGAAGTATTTCCTGTAACTATAGAAAGAATTATGTATATATACATGCAGAAATATATA
	TGTGTGTGTGTATCTGTGGATGGATATATGTATATCTCTTCCTATATATATCCATAGT
	GGACTTATTCAGAACATAGATATGTATTCAGCTTGTC
	ORF Start: ATG at 118		ORF Stop: TAG at 3154
	SEQ ID NO:108	1012 aa	MW at 113790.3 Da
NOV25a,	MRWGLRPRGPGAAALATARSLWGTPRLPCSPGWQGATKRLLVRSVSGASNHQPNSNSG
CG120563-01	RYRDTVLLPQTSFPMKLLGRQQPDTELEIQQKCGFSELYSWQRERKVKTEFCLHDGPP
Protein Sequence	YANGDPHVGHALNKILKDIANRFHMMNGSKIHFVPGWDCHGLPIEIKVLSELGREAQN
	LSAMEIRKKARSFAKAAIEKQKSAFIRWGIMADWNNCYYTFDGKYEAKQLRTFYQMYD
	KGLVYRSYKPVFWSPSSRTALAEAELEYNPEHVSRSIYVKFPLLKPSPKLASLIDGSS
	PVSILVWTTQPWTIPANEAVCYMPESKYAVVKCSKSGDLYVLAADKVASVASTLETTF
	ETISTLSGVDLENGTCSHPLIPDKASPLLPANHVTMAKGTGLVHTAPAHGMEDYGVAS
	QHNLPMDCLVDEDGVFTDVAGPELQNKAVLEEGTDVVIKMLQTAKNLLKEEKLVHSYP
	YDWRTKKPVVIRASKQWFINITDIKTAAKELLKKVKFIPGSALNGMVEMMDRRPYWCI
	SRQRVWGVPIPVFHHKTKDEYLINSQTTEHIVKLVEQHGSDIWWTLPPEQLLPKEVLS
	EVGGPDALEYVPGQDILDIWFDSGTSWSYVLPGPDQRADLYLEGKDQLGGWFQSSLLT
	SVAARKRAPYKTVIVHGFTLGEKGEKMSKSLGNVIHPDVVVNGGQDQSKEPPYGADVL
	RWWVADSNVFTEVAIGPSVLNAARDDISKLRNTLRFLLGNVADFNPETDSIPVNDMYV
	IDQYMLHLLQDLANKITELYKQYDFGKVVRLLRTFYTRELSNFYFSIIKDRLYCEKEN
	DPKRRSCQTALVEILDVIVRSFAPILPHLAEEVFQHIPYIKEPKSVFRTGWISTSSIW
	KKPGLEEAVESACAMRDSFLGSIPGKNAAEYKVITVIEPGLLFEIIEMLQSEETSSTS
	QLNELMMASESTLLAQEPREMTADVIELKGKFLINLEGGDIREESSYKVIVMPTTKEK
	CPRCWKYTAESSDTLCPRCAEVVSGK
	SEQ ID NO:109	3201 bp
NOV25b,	CCCTCTTACTCGGCTCCCCTTGGTTTCCTGGGGTCCTGCCCCTTCAAGCTGGGGCGGG
CG120563-02 DNA	AGCGGAGGACCCCGCTCTCAGGGGTTGCCGGACCATGCGTTGGGGGCTGCGCCCTCGC
Sequence	GGGCCGGGCGCGGCCGCCCTGGCCACTGCCCGAAGTTTGTGGGGGACGCCCCGCCTTC
	CCTGCAGCCCGGGATGGCAAGGGGCGACGAAGAGGCTTCTGGTGCGGTCGGTCTCCGG
	GGCCAGTAACCACCAGCCGAACTCGAATAGTGGCAGATACCGGGACACGGTGCTGCTG
	CCGCAGACGAGCTTCCCCATGAAGCTGCTGGGCCGCCAGCAGCCGGACACGGAGCTGG
	AGATCCAGCAGAAATGTGGATTTTCAGAACTTTATTCATGGCAAAGAGAAAGAAAAGT
	AAAGACAGAATTTTGCCTTCATGATGGACCTCCTTATGCAAACGGTGACCCTCATGTT
	GGACATGCTTTAAATAAGATTTTGAAAGACATAGCCAATCGATTCCATATGATGAATG
	GCTCCAAAATACATTTTGTGCCCGGCTGGGATTGTCATGGGTTGCCCATTGAAATAAA
	AGTATTATCAGAACTTGGTAGAGAAGCTCAGAATCTTTCAGCTATGGAAATTAGAAAG
	AAAGCTAGATCATTTGCTAAAGCAGCCATTGAGAAACAGAAATCAGCATTTATTCGTT
	GGGGAATAATGGCAGATTGGAATAATTGCTACTATACATTTGATGGGAAGTATGAAGC
	CAAACAGTTGAGAACTTTTTACCAAATGTATGATAAGGGCTTGGTTTATCGATCTTAC
	AAACCTGTGTTTTGGTCTCCGTCATCTAGGACTGCATTGGCTGAAGCAGAACTTGAAT
	ATAATCCTGAGCATGTCAGTCGTTCAATATATGTAAAATTTCCTCTCTTAAAGCCTTC
	TCCAAAATTGGCATCTCTTATAGATGGTTCATCTCCTGTTAGTATTTTGGTCTGGACC
	ACACAACCTTGGACGATTCCAGCCAATGAAGCTGTTTGCTATATGCCTGAATCAAAGT
	ATGCTGTTGTGAAATGTTCTAAGTCTGGAGACCTCTACGTACTGGCGGCAGATAAAGT
	AGCATCTGTTGCTTCTACTTTGGAAACAACATTTGAGACTATTTCAACACTTTCAGGT
	GTAGATTTGGAAAATGGTACTTGCAGTCATCCATTAATTCCTGATAAAGCCTCTCCTC
	TTTTACCTGCAAATCATGTGACCATGGCAAAAGGAACGGGATTGGTTCACACAGCCCC
	AGCTCATGGTGTGGAAGACTACGGTGTAGCGTCTCAGCACAACCTGCCCATGGATTGT
	CTAGTGGACGAAGATGGAGTTTTCACAGATGTTGCAGGTCCTGAACTTCAAAACAAGG
	CTGTCCTTGAAGAGGGAACTGATGTGGTTATAAAGATGCTTCAGACTGCAAAGAATTT
	GTTGAAAGAGGAGAAATTGGTGCATAGCTATCCGTATGACTGGAGGACCAAGAAACCT
	GTGGTTATTCGTGCCAGCAAGCAGTGGTTTATAAACATCACGGATATTAAGACTGCAG
	CCAAGGAATTGTTAAAAAAGGTGAAATTTATTCCTGGATCAGCACTGAATGGCATGGT
	TGAAATGATGGACAGGCGGCCATATTGGTGTATATCAAGGCAAAGAGTTTGGGGTGTT
	CCAATTCCTGTGTTTCATCATAAGACCAAGGATGAATACTTGATCAACAGCCAAACCA
	CTGAGCATATTGTTAAACTAGTGGAACAACACGGCAGTGATATCTGGTGGACTCTTCC
	CCCTGAACAACTTCTTCCAAAAGAAGTCTTATCTGAGGTTGGTGGCCCTGATGCCTTG
	GAATATGTGCCAGGTCAGGATATTTTGGACATCTGGTTTGATAGCGGAACTTCATGGT
	CTTATGTTCTTCCAGGTCCTGACCAAAGAGCAGATTTGTACTTGGAAGGAAAAGACCA
	GCTCGGGGGTTGGTTTCAGTCATCCTTATTAACAAGTGTGGCAGCAAGGAACAGAGCA
	CCTTATAAGACAGTGATTGTTCATGGATTTACCCTTGGAGAAAAGGGAGAAAAGATGT
	CCAAGTCTCTTGGGAATGTCATTCATCCTGATGTTGTCGTTAATGGAGGACAAGATCA
	AAGCAAAGAGCCTCCGTATGGTGCTGATGTCCTTCGCTGGTGGGTAGCTGATTCCAAT
	GTCTTCACCGAAGTTGCAATTGGCCCATCCGTGCTCAATGCTGCCAGAGATGATATTA
	GCAAGCTTAGGAATACACTTCGCTTTCTTTTGGGAAATGTGGCTGATTTCAACCCAGA
	AACAGATTCCATCCCTGTAAACGATATGTATGTCATAGACCAGTACATGCTACACTTA
	CTGCAGGATTTGGCAAACAAGATTACCGAATTATACAAACAATATGATTTTGGAAAAG
	TTGTTCGGCTGTTACGGACGTTTTATACCAGAGAGCTCTCTAACTTTTATTTCAGTAT
	AATCAAAGATAGGCTCTATTGTGAAAAGGAAAATGACCCCAAACGACGCTCTTGTCAG
	ACTGCATTAGTTGAAATTTTGGATGTAATAGTTCGTTCTTTTGCTCCCATTCTTCCTC
	ACCTGGCTGAAGAGGTGTTCCAGCACATACCTTATATTAAAGAGCCCAAGAGTGTTTT
	CCGTACTGGGTGGATTAGTACTAGTTCTATCTGGAAAAAGCCCGGGTTGGAAGAAGCT
	GTGGAGAGTGCGTGTGCAATGCGAGACTCATTTCTTGGAAGCATCCCTGGCAAAAATG
	CAGCTGAGTACAAGGTTATCACTGTGATAGAACCTGGACTGCTTTTTGAGATAATAGA
	GATGCTGCAGTCTGAAGAGACTTCCAGCACCTCTCAGTTGAATGAATTAATGATGGCT
	TCTGAGTCAACTTTACTGGCTCAGGAACCACGAGAGATGACTGCAGATGTAATCGAGC
	TTAAAGGGAAATTCCTCATCAACTTAGAAGGTGGTGATATTCGTGAAGAGTCTTCCTA
	TAAAGTAATTGTCATGCCGACTACGAAAGAAAAATGCCCCCGTTGTTGGAAGTATACA
	GCGGAGTCTTCAGATACACTGTGTCCTCGATGTGCAGAAGTTGTCAGTGGAAAATAGT
	ATTAACAGCTCACTCGAGCAAGAACCCTCCTGACAGTACTGGCTGGAAGTTTGGATGG
	ATTATTTACAA
	ORF Start: ATG at 93		ORF Stop: TAG at 3129
	SEQ ID NO: 110	1012 aa	MW at 113758.2 Da
NOV25b,	MRWGLRPRGPGAAALATARSLWGTPRLPCSPGWQGATKRLLVRSVSGASNHQPNSNSG
CG120563-02	RYRDTVLLPQTSFPMKLLGRQQPDTELEIQQKCGFSELYSWQRERKVKTEFCLHDGPP
Protein Sequence	YANGDPHVGHALNKILKDIANRFHMMNGSKIHFVPGWDCHGLPIEIKVLSELGREAQN
	LSAMEIRKKARSFAKAAIEKQKSAFIRWGIMADWNNCYYTFDGKYEAKQLRTFYQMYD
	KGLVYRSYKPVFWSPSSRTALAEAELEYNPEHVSRSIYVKFPLLKPSPKLASLIDGSS
	PVSILVWTTQPWTIPANEAVCYMPESKYAVVKCSKSGDLYVLAADKVASVASTLETTF
	ETISTLSGVDLENGTCSHPLIPDKASPLLPANHVTMAKGTGLVHTAPAHGVEDYGVAS
	QHNLPMDCLVDEDGVFTDVAGPELQNKAVLEEGTDVVIKMLQTAKNLLKEEKLVHSYP
	YDWRTKKPVVIRASKQWFINITDIKTAAKELLKKVKFIPGSALNGMVEMMDRRPYWCI
	SRQRVWGVPIPVFHHKTKDEYLINSQTTEHIVKLVEQHGSDIWWTLPPEQLLPKEVLS
	EVGGPDALEYVPGQDILDIWFDSGTSWSYVLPGPDQRADLYLEGKDQLGGWFQSSLLT
	SVAARKRAPYKTVIVHGFTLGEKGEKMSKSLGNVIHPDVVVNGGQDQSKEPPYGADVL
	RWWVADSNVFTEVAIGPSVLNAARDDISKLRNTLRFLLGNVADFNPETDSIPVNDMYV
	IDQYMLHLLQDLANKITELYKQYDFGKVVRLLRTFYTRELSNFYFSIIKDRLYCEKEN
	DPKRRSCQTALVEILDVIVRSFAPILPHLAEEVFQHIPYIKEPKSVFRTGWISTSSIW
	KKPGLEEAVESACAMRDSFLGSIPGKNAAEYKVITVIEPGLLFEIIEMLQSEETSSTS
	QLNELMMASESTLLAQEPREMTADVIELKGKFLINLEGGDIREESSYKVIVMPTTKEK
	CPRCWKYTAESSDTLCPRCAEVVSGK

[0448] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 25B.

TABLE 25B
Comparison of NOV25a against NOV25b.
Protein	NOV25a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV25b	1 . . . 1012	1000/1012 (98%)
	1 . . . 1012	1001/1012 (98%)

[0449] Further analysis of the NOV25a protein yielded the following properties shown in Table 25C.

TABLE 25C
Protein Sequence Properties NOV25a
PSort     0.5051 probability located in mitochondrial matrix space;
analysis: 0.4178 probability located in microbody (peroxisome); 0.3000
          probability located in nucleus; 0.2267 probability located in
          mitochondrial inner membrane
SignalP   Cleavage site between residues 24 and 25
analysis:

[0450] A search of the NOV25a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 25D.

TABLE 25D
Geneseq Results for NOV25a
		NOV25a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAW48720	Human mitochondrial isoleucyl-	20 . . . 1012	993/993 (100%)	0.0
	tRNA synthetase - Homo sapiens,	1 . . . 993	993/993 (100%)
	993 aa. [U.S. Pat. No. 5759833-A, 02 JUN. 1998]
AAM78687	Human protein SEQ ID NO 1349 -	73 . . . 890	809/818 (98%)	0.0
	Homo sapiens, 833 aa.	1 . . . 818	809/818 (98%)
	[WO200157190-A2, 09 AUG. 2001]
AAB92698	Human protein sequence SEQ ID	142 . . . 878	737/737 (100%)	0.0
	NO: 11094 - Homo sapiens, 764 aa.	1 . . . 737	737/737 (100%)
	[EP1074617-A2, 07 FEB. 2001]
AAB34842	Human secreted protein sequence	282 . . . 887	605/606 (99%)	0.0
	encoded by gene 42 SEQ ID NO: 130 -	1 . . . 606	606/606 (99%)
	Homo sapiens, 606 aa.
	[WO200058356-A1, 05 OCT. 2000]
AAB94166	Human protein sequence SEQ ID	446 . . . 1012	565/567 (99%)	0.0
	NO: 14466 - Homo sapiens, 567 aa.	1 . . . 567	565/567 (99%)
	[EP1074617-A2, 07 FEB. 2001]

[0451] In a BLAST search of public sequence datbases, the NOV25a protein was found to have homology to the proteins shown in the BLASTP data in Table 25E.

TABLE 25E
Public BLASTP Results for NOV25a
		NOV25a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9NSE4	Mitochondrial isoleucine tRNA	20 . . . 1012	993/993 (100%)	0.0
	synthetase - Homo sapiens (Human),	1 . . . 993	993/993 (100%)
	993 aa (fragment).
Q9NW42	CDNA FLJ10326 fis, clone	142 . . . 878	737/737 (100%)	0.0
	NT2RM2000577, weakly similar to	1 . . . 737	737/737 (100%)
	isoleucyl-tRNA synthetase (EC
	6.1.1.5) - Homo sapiens (Human),
	764 aa.
Q9H9Q8	CDNA FLJ12603 fis, clone	446 . . . 1012	565/567 (99%)	0.0
	NT2RM4001444, weakly similar to	1 . . . 567	565/567 (99%)
	isoleucyl-tRNA synthetase (EC
	6.1.1.5) - Homo sapiens (Human),
	567 aa.
Q8R2M5	Hypothetical 60.1 kDa protein - Mus	477 . . . 1012	448/536 (83%)	0.0
	musculus (Mouse), 536 aa	1 . . . 536	494/536 (91%)
	(fragment).
P73505	Isoleucyl-tRNA synthetase (EC	60 . . . 1011	419/998 (41%)	0.0
	6.1.1.5) (Isoleucine−-tRNA ligase)	7 . . . 986	576/998 (56%)
	(IleRS) - Synechocystis sp. (strain
	PCC 6803), 988 aa.

[0452] PFam analysis predicts that the NOV25a protein contains the domains shown in the Table 25F.

TABLE 25F
Domain Analysis of NOV25a
		Identities/
	NOV25a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
tRNA-synt_1e	661 . . . 673	10/13 (77%)	0.068
		13/13 (100%)
tRNA-synt_1	86 . . . 771	254/813 (31%)	4.6e−185
		499/813 (61%)

Example 26

[0453] The NOV26 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 26A.

TABLE 26A
NOV26 Sequence Analysis
	SEQ ID NO:111	501 bp
NOV26a,	CAATGTCCGAGTCCAAGAACGGCCCCGAGTATGCTTCGTTTTTCGCCGTCATGGCAGC
CG122872-01 DNA	CTCGGCCGCCATGGTCTTCAGCGCCCCGCGCGCTGCCTATGGCACGGTCAAGACCGGT
Sequence	GCCGGCATCGCGGCCATGTCTGTCATGCGGCCGGAGCTGATCATGAAGTCCATCATCC
	CGGTGGTCACGGCTGGCATCATCGCCATCTATGGCCTGGTGGTGACAGTCCTCATCGC
	CAGCTCCCCGAATGACGACATCAGCCTCTACAGGAGCTGCCTCCAGCTAGCCGGCCTG
	AGCGTGGGCCTGAGCGGCCTGGCAGCCGGCTTTGCCATAGACATCTTGGGGGACGCCG
	GTGTGCGAGCCACGGCCCAGCAGCCCCGACTATTCATGGGCATGATCCTGATCCTCAT
	CTTCCCCGAGGTGCTCGGCCTGTACGGTCTCGTCGTTGCCCTCATCCTCTCCACAGAG
	TAGCCCCTCTCCGAGCCCACCAGCCACCGAATATGAT
	ORF Start: ATG at 3		ORF Stop: TAG at 465
	SEQ ID NO:112	154 aa	MW at 15871.6 Da
NOV26a,	MSESKNGPEYASFFAVMAASAAMVFSAPRAAYGTVKTGAGIAAMSVMRPELIMKSIIP
CG122872-01	VVTAGIIAIYGLVVTVLIASSPNDDISLYRSCLQLAGLSVGLSGLAAGFAIDILGDAG
Protein Sequence	VRATAQQPRLFMGMILILIFPEVLGLYGLVVALILSTE

[0454] Further analysis of the NOV26a protein yielded the following properties shown in Table 26B.

TABLE 26B
Protein Sequence Properties NOV26a
PSort     0.6850 probability located in endoplasmic reticulum
analysis: (membrane); 0.6400 probability located in plasma
          membrane; 0.4600 probability located in Golgi body;
          0.1000 probability located in endoplasmic reticulum (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0455] A search of the NOV26a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 26C.

TABLE 26C
Geneseq Results for NOV26a
		NOV26a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU08592	Human V-ATPase 16kDa subunit -	1 . . . 154	133/155 (85%)	2e−64
	Homo sapiens, 155 aa.	1 . . . 155	141/155 (90%)
	[WO200162912-A2, 30 AUG. 2001]
AAB43446	Human cancer associated protein	1 . . . 154	130/155 (83%)	1e−62
	sequence SEQ ID NO: 891 - Homo	44 . . . 198	138/155 (88%)
	sapiens, 198 aa. [WO200055350-A1,
	21 SEP. 2000]
AAB58779	Breast and ovarian cancer associated	30 . . . 154	108/126 (85%)	1e−50
	antigen protein sequence SEQ ID 487 -	37 . . . 162	115/126 (90%)
	Homo sapiens, 162 aa.
	[WO200055173-A1, 21 SEP. 2000]
ABB66590	Drosophila melanogaster polypeptide	4 . . . 154	109/154 (70%)	2e−50
	SEQ ID NO 26562 - Drosophila	6 . . . 159	124/154 (79%)
	melanogaster, 159 aa.
	[WO200171042-A2, 27 SEP. 2001]
ABB60102	Drosophila melanogaster polypeptide	4 . . . 154	109/154 (70%)	2e−50
	SEQ ID NO 7098 - Drosophila	6 . . . 159	124/154 (79%)
	melanogaster, 159 aa.
	[WO200171042-A2, 27 SEP. 2001]

[0456] In a BLAST search of public sequence datbases, the NOV26a protein was found to have homology to the proteins shown in the BLASTP data in Table 26D.

TABLE 26D
Public BLASTP Results for NOV26a
		NOV26a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P23956	Vacuolar ATP synthase 16 kDa	1 . . . 154	133/155 (85%)	4e−64
	proteolipid subunit (EC 3.6.3.14) -	1 . . . 155	141/155 (90%)
	Bos taurus (Bovine), 155 aa.
P27449	Vacuolar ATP synthase 16 kDa	1 . . . 154	133/155 (85%)	6e−64
	proteolipid subunit (EC 3.6.3.14) -	1 . . . 155	141/155 (90%)
	Homo sapiens (Human), 155 aa.
O18882	Vacuolar ATP synthase 16 kDa	1 . . . 154	132/155 (85%)	1e−63
	proteolipid subunit (EC 3.6.3.14) -	1 . . . 155	141/155 (90%)
	Ovis aries (Sheep), 155 aa.
P23967	Vacuolar ATP synthase 16 kDa	1 . . . 154	126/155 (81%)	2e−60
	proteolipid subunit (EC 3.6.3.14) -	1 . . . 155	137/155 (88%)
	Mus musculus (Mouse), and, 155 aa.
PXBOV6	H + transporting ATPase (EC	1 . . . 154	125/155 (80%)	4e−58
	3.6.1.35), vacuolar, 16K chain -	1 . . . 155	133/155 (85%)
	bovine, 155 aa.

[0457] PFam analysis predicts that the NOV26a protein contains the domains shown in the Table 26E.

TABLE 26E
Domain Analysis of NOV26a
		Identities/
	NOV26a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
ATP-synt_C	14 . . . 79	22/70 (31%)	7.2e−09
		55/70 (79%)
ATP-synt_C	94 . . . 154	26/70 (37%)	8.9e−15
		54/70 (77%)

Example 27

[0458] The NOV27 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 27A.

TABLE 27A
NOV27 Sequence Analysis
	SEQ ID NO:113	2731 bp
NOV27a,	ATTTTGGGACATGGCCACTGCTTCACCAAGGTCTGATACTAGTAATAACCACAGTGGA
CG122909-01 DNA	AGGTTGCAGTTACAGGTAACTGTTTCTAGTGCCAAACTTAAAAGAAAAAAGAACTGGT
Sequence	TCGGAACAGCAATATATACAGAAGTAGTTGTAGATGGAGAAATTACGAAAACAGCAAA
	ATCCAGTAGTTCTTCTAATCCAAAATGGGATGAACAGCTAACTGTAAATGTTACGCCA
	CAGACTACATTGGAATTTCAAGTTTGGAGCCATCGCACTTTAAAAGCAGATGCTTTAT
	TAGGAAAAGCAACGATAGATTTGAAACAAGCTCTGTTGATACACAATAGAAAATTGGA
	AAGAGTGAAAGAACAATTAAAACTTTCCTTGGAAAACAAGAATGGCATAGCACAAACT
	GGTGAATTGACAGTTGTGCTTGATGGATTGGTGATTGAGCAAGAAAATATAACAAACT
	GCAGCTCATCTCCAACCATAGAAATACAGGAAAATGGTGATGCCTTACATGAAAATGG
	AGAGCCTTCAGCAAGGACAACTGCCAGGTTGGCTGTTGAAGGCACGAATGGAATAGAT
	AATCATGTACCTACAAGCACTCTAGTCCAAAACTCATGCTGCTCGTATGTAGTTAATG
	GAGACAACACACCTTCATCTCCGTCTCAGGTTGCTGCCAGACCCAAAAATACACCAGC
	TCCAAAACCACTCGCATCTGAGCCTGCCGATGACACTGTTAATGGAGAATCATCCTCA
	TTTGCACCAACTGATAATGCGTCTGTCACGGGTACTCCAGTAGTGTCTGAAGAAAATG
	CCTTGTCTCCAAATTGCACTAGTACTACTGTTGAAGATCCTCCAGTTCAAGAAATACT
	GACTTCCTCAGAAAACAATGAATGTATTCCTTCTACCAGTGCAGAATTGGAATCTGAA
	GCTAGAAGTATATTAGAGCCTGACACCTCTAATTCTAGAAGTAGTTCTGCTTTTGAAG
	CAGCCAAATCAAGACAGCCAGATGGGTGTATGGATCCTGTACGGCAGCAGTCTGGGAA
	TGCCAACACAGAAACCTTGCCATCAGGGTGGGAACAAAGAAAAGATCCTCATGGTAGA
	ACCTATTATGTGGATCATAATACTCGAACTACCACATGGGAGAGACCACAACCTTTAC
	CTCCAGGTTGGGAAAGAAGAGTTGATGATCGTAGAAGAGTTTATTATGTGGATCATAA
	CACCAGAACAACAACGTGGCAGCGGCCTACCATGGAATCTGTCCGAAATTTTGAACAG
	TGGCAATCTCAGCGGAACCAATTGCAGGGAGCTATGCAACAGTTTAACCAACGATACC
	TCTATTCGGCTTCAATGTTAGCTGCAGAAAATGACCCTTATGGACCTTTGCCACCAGG
	CTGGGAAAAAAGAGTGGATTCAACAGACAGGGTTTACTTTGTGAATCATAACACAAAA
	ACAACCCAGTGGGAAGATCCAAGAACTCAAGGCTTACAGAATGAAGAACCCCTGCCAG
	AAGGCTGGGAAATTAGATATACTCGTGAAGGTGTAAGGTACTTTGTTGATCATAACAC
	AAGAACAACAACATTCAAAGATCCTCGCAATGGGAAGTCATCTGTAACTAAAGGTGGT
	CCACAAATTGCTTATGAACGCGGCTTTAGGTGGAAGCTTGCTCACTTCCGTTATTTGT
	GCCAGATTATGGCATTAAAACCCTATGACTTGAGGAGGCGCTTATATGTAATATTTAG
	AGGAGAAGAAGGACTTGATTATGGTGGCCTAGCGAGAGAATGGTTTTTCTTGCTTTCA
	CATGAAGTTTTGAACCCAATGTATTGCTTATTTGAGTATGCGGGCAAGAACAACTATT
	GTCTGCAGATAAATCCAGCATCAACCATTAATCCAGACCATCTTTCATACTTCTGTTT
	CATTGGTCGTTTTATTGCCATGGCACTATTTCATGGAAAGTTTATCGATACTGGTTTC
	TCTTTACCATTCTACAAGCGTATGTTAAGTAAAAAACTTACTATTAAGGATTTGGAAT
	CTATTGATACTGAATTTTATAACTCCCTTATCTGGATAAGAGATAACAACATTGAAGA
	ATGTGGCTTAGAAATGTACTTTTCTGTTGACATGGAGATTTTGGGAAAAGTTACTTCA
	CATGACCTGAAGTTGGGAGGTTCCAATATTCTGGTGACTGAGGAGAACAAAGATGAAT
	ATATTGGTTTAATGACAGAATGGCGTTTTTCTCGAGGAGTACAAGAACAGACCAAAGC
	TTTCCTTGATGGTTTTAATGAAGTTGTTCCTCTTCAGTGGCTACAGTACTTCGATGAA
	AAAGAATTAGAGGTTATGTTGTGTGGCATGCAGGAGGTTGACTTGGCAGATTGGCAGA
	GAAATACTGTTTATCGACATTATACAAGAAACAGCAAGCAAATCATTTGGTTTTGGCA
	GTTTGTGAAAGAGACAGACAATGAAGTAAGAATGCGACTATTGCAGTTCGTCACTGGA
	ACCTGCCGTTTACCTCTAGGAGGATTTGCTGAGCTCATGGGAAGTAATGGGCCTCAAA
	AGTTTTGCATTGAAAAAGTTGGCAAAGACACTTGGTTACCAAGAAGCCATACATGTTT
	TAATCGCTTGGATCTACCACCATATAAGAGTTATGAACAACTAAAGGAAAAACTTCTT
	TTTGCAATAGAAGAGACAGAGGGATTTGGACAAGAATGAATGTGGCTTCTTATTTTGG
	AGGAG
	ORF Start: ATG at 11		ORF Stop: TGA at 2705
	SEQ ID NO:114	898 aa	MW at 102472.8 Da
NOV27a,	MATASPRSDTSNNHSGRLQLQVTVSSAKLKRKKNWFGTAIYTEVVVDGEITKTAKSSS
CG122909-01	SSNPKWDEQLTVNVTPQTTLEFQVWSHRTLKADALLGKATIDLKQALLIHNRKLERVK
Protein Sequence	EQLKLSLENKNGIAQTGELTVVLDGLVIEQENITNCSSSPTIEIQENGDALHENGEPS
	ARTTARLAVEGTNGIDNHVPTSTLVQNSCCSYVVNGDNTPSSPSQVAARPKNTPAPKP
	LASEPADDTVNGESSSFAPTDNASVTGTPVVSEENALSPNCTSTTVEDPPVQEILTSS
	ENNECIPSTSAELESEARSILEPDTSNSRSSSAFEAAKSRQPDGCMDPVRQQSGNANT
	ETLPSGWEQRKDPHGRTYYVDHNTRTTTWERPQPLPPGWERRVDDRRRVYYVDHNTRT
	TTWQRPTMESVRNFEQWQSQRNQLQGAMQQFNQRYLYSASMLAAENDPYGPLPPGWEK
	RVDSTDRVYFVNHNTKTTQWEDPRTQGLQNEEPLPEGWEIRYTREGVRYFVDHNTRTT
	TFKDPRNGKSSVTKGGPQIAYERGFRWKLAHFRYLCQIMALKPYDLRRRLYVIFRGEE
	GLDYGGLAREWFFLLSHEVLNPMYCLFEYAGKNNYCLQINPASTINPDHLSYFCFIGR
	FIAMALFHGKFIDTGFSLPFYKRMLSKKLTIKDLESIDTEFYNSLIWIRDNNIEECGL
	EMYFSVDMEILGKVTSHDLKLGGSNILVTEENKDEYIGLMTEWRFSRGVQEQTKAFLD
	GFNEVVPLQWLQYFDEKELEVMLCGMQEVDLADWQRNTVYRHYTRNSKQIIWFWQFVK
	ETDNEVRMRLLQFVTGTCRLPLGGFAELMGSNGPQKFCIEKVGKDTWLPRSHTCFNRL
	DLPPYKSYEQLKEKLLFAIEETEGFGQE

[0459]

TABLE 27B
Protein Sequence Properties NOV27a
PSort     0.3972 probability located in microbody (peroxisome); 0.3000
analysis: probability located in nucleus; 0.1000 probability located in
          mitochondrial matrix space; 0.1000 probability located in
          lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0460] A search of the NOV27a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 27C.

TABLE 27C
Geneseq Results for NOV27a
		NOV27a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB05708	Human signal transduction protein	1 . . . 898	898/922 (97%)	0.0
	clone tes3_11d21 - Homo sapiens,	1 . . . 922	898/922 (97%)
	922 aa. [WO200198454-A2, 27 DEC 2001]
AAB50049	Human homolog of Drosophila	1 . . . 898	898/922 (97%)	0.0
	suppressor of deltex - Homo sapiens,	1 . . . 922	898/922 (97%)
	922 aa. [WO200073329-A2, 07 DEC. 2000]
AAB50048	Human clone 8IIIa protein - Homo	190 . . . 898	709/733 (96%)	0.0
	sapiens, 733 aa. [WO200073329-A2,	1 . . . 733	709/733 (96%)
	07 DEC. 2000]
AAE05494	Human ubiquitin protein ligase	191 . . . 847	656/681 (96%)	0.0
	WWP1 - Homo sapiens, 683 aa.	2 . . . 682	657/681 (96%)
	[U.S. Pat. No. 6258601-B1, 10 JUL. 2001]
AAW36794	Novel human protein, designated	191 . . . 847	656/681 (96%)	0.0
	WWP1, which contains WW domains -	2 . . . 682	657/681 (96%)
	Homo sapiens, 683 aa.
	[WO9737223-A1, 09 OCT. 1997]

[0461] In a BLAST search of public sequence datbases, the NOV27a protein was found to have homology to the proteins shown in the BLASTP data in Table 27D.

TABLE 27D
Public BLASTP Results for NOV27a
		NOV27a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9H0M0	Hypothetical 105.2 kDa protein	1 . . . 898	898/922 (97%)	0.0
	(WW domain-containing protein 1) -	1 . . . 922	898/922 (97%)
	Homo sapiens (Human), 922 aa.
O00307	WWP1 - Homo sapiens (Human),	191 . . . 847	656/681 (96%)	0.0
	684 aa (fragment).	2 . . . 682	657/681 (96%)
Q96F66	Similar to itchy (mouse homolog) E3	19 . . . 898	538/924 (58%)	0.0
	ubiquitin protein ligase - Homo	19 . . . 903	644/924 (69%)
	sapiens (Human), 903 aa.
Q96CZ2	Nedd-4-like ubiquitin-protein ligase -	19 . . . 898	529/919 (57%)	0.0
	Homo sapiens (Human), 870 aa.	19 . . . 870	634/919 (68%)
O00308	WWP2 - Homo sapiens (Human),	19 . . . 898	527/919 (57%)	0.0
	870 aa.	19 . . . 870	632/919 (68%)

[0462] PFam analysis predicts that the NOV27a protein contains the domains shown in the Table 27E.

TABLE 27E
Domain Analysis of NOV27a
		Identities/
	NOV27a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
C2	20 . . . 98	23/97 (24%)	0.019
		53/97 (55%)
WW	351 . . . 380	20/30 (67%)	9.6e−16
		30/30 (100%)
WW	383 . . . 412	17/30 (57%)	6e−13
		27/30 (90%)
WW	458 . . . 487	20/30 (67%)	6.3e−15
		27/30 (90%)
WW	498 . . . 527	13/30 (43%)	1.2e−10
		25/30 (83%)
HECT	593 . . . 898	149/358 (42%)	5.6e−127
		235/358 (66%)

Example 28

[0463] The NOV28 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 28A.

TABLE 28A
NOV28 Sequence Analysis
	SEQ ID NO:115	1557 bp
NOV28a,	ACCTCTCACTATGACCGCGGCCGCCGCCTCCAACTGGGGGCTGATCACGAACATCGTG
CG123772-01 DNA	AACAGCATCGTAGGGGTCAGTGTCCTCACCATGCCCTTCTGCTTCAAACAGTGCGGCA
Sequence	TCGTCCTGGGGGCGCTGCTCTTGGTCTTCTGCTCATGGATGACGCACCAGTCGTGCAT
	GTTCTTGGTGAAGTCGGCCAGCCTGAGCAAGCGGAGGACCTACGCCGGCCTGGCATTC
	CACGCCTACGGGAAGGCAGGCAAGATGCTGGTGGAGACCAGCATGATCGGGCTGATGC
	TGGGCACCTGCATCGCCTTCTACGTCGTGATCGGCGACTTGGGGTCCAACTTCTTTGC
	CCGGCTGTTCGGGTTTCAGGTGGGCGGCACCTTCCGCATGTTCCTGCTGTTCGCCGTG
	TCGCTGTGCATCGTGCTCCCGCTCAGCCTGCAGCGGAACATGATGGCCTCCATCCAGT
	CCTTCAGCGCCATGGCCCTCCTCTTCTACACCGTGTTCATGTTCGTGATCGTGCTCTC
	CTCTCTCAAGCACGGCCTCTTCAGTGGGCAGTGGCTGCGGCGGGTCAGCTACGTCCGC
	TGGGAGGGCGTCTTCCGCTGCATCCCCATCTTCGGCATGTCCTTCGCCTGCCAGTCGC
	AGGTGCTGCCCACCTACGACAGCCTGGATGAGCCGTCAGTGAAAACCATGAGCTCCAT
	ATTTGCTTCCTCCCTTAATGTGGTCACCACCTTCTACGTCATGGTGGGGTTTTTCGGC
	TACGTCAGCTTCACCGAGGCCACGGCCGGCAACGTGCTCATGCACTTTCCCTCCAACC
	TGGTGACGGAGATGCTCCGTGTGGGCTTCATGATGTCAGTGGCTGTGGGCTTCCCCAT
	GATGATCCTGCCATGCAGGCAGGCCCTGAGCACGCTGCTGTGTGAGCAGCAGCAAAAA
	GATGGCACCTTTGCAGCAGGGGGCTACATGCCCCCTCTCCGGTTTAAAGCACTTACCC
	TCTCTGTGGTGTTTGGAACCATGGTTGGTGGCATCCTTATCCCCAACGTGGAGACCAT
	CCTGGGCCTCACAGGAGCGACCATGGGAAGCCTCATCTGCTTCATCTGCCCGGCGCTG
	ATCTACAAGAAAATCCACAAGAACGCACTTTCCTCCCAGGTGGTGCTGTGGGTCGGCC
	TGGGCGTCCTGGTGGTGAGCACTGTCACCACACTGTCTGTGAGCGAGGAGGTCCCCGA
	GGACTTGGCAGAGGAAGCCCCTGGCGGCCGGCTTGGAGAGGCCGAGGGTTTGATGAAG
	GTGGAGGCAGCGCGGCTCTCAGCCCAGGATCCGGTTGTGGCCGTGGCTGAGGATGGCC
	GGGAGAAGCCGAAGCTGCCGAAGGAGAGAGAGGAGCTGGAGCAGGCCCATATCAAGGG
	GCCCGTGGATGTGCCTGGACGGGAAGATGGCAAGGAGGCACCGGAGGAGGCACAGCTC
	GATCGCCCTGGGCAAGGGATTGCTGTGCCTGTGGGCGAGGCCCACCGCCACCAGCCTC
	CTGTTCCTCACGACAAGGTGGTGGGTAGATGAAAGCCAAGACCGAGAGG
	ORF Start: ATG at 11		ORF Stop: TGA at 1538
	SEQ ID NO:116	509 aa	MW at 55201.5 Da
NOV28a,	MTAAAASNWGLITNIVNSIVGVSVLTMPFCFKQCGIVLGALLLVFCSWMTHQSCMFLV
CG123772-01	KSASLSKRRTYAGLAFHAYGKAGKMLVETSMIGLMLGTCIAFYVVIGDLGSNFFARLF
Protein Sequence	GFQVGGTFRMFLLFAVSLCIVLPLSLQRNMMASIQSFSAMALLFYTVFMFVIVLSSLK
	HGLFSGQWLRRVSYVRWEGVFRCIPIFGMSFACQSQVLPTYDSLDEPSVKTMSSIFAS
	SLNVVTTFYVMVGFFGYVSFTEATAGNVLMHFPSNLVTEMLRVGFMMSVAVGFPMMIL
	PCRQALSTLLCEQQQKDGTFAAGGYMPPLRFKALTLSVVFGTMVGGILIPNVETILGL
	TGATMGSLICFICPALIYKKIHKNALSSQVVLWVGLGVLVVSTVTTLSVSEEVPEDLA
	EEAPGGRLGEAEGLMKVEAARLSAQDPVVAVAEDGREKPKLPKEREELEQAHIKGPVD
	VPGREDGKEAPEEAQLDRPGQGIAVPVGEAHRHQPPVPHDKVVGR

[0464] Further analysis of the NOV28a protein yielded the following properties shown in Table 28B.

TABLE 28B
Protein Sequence Properties NOV28a
PSort     0.6400 probability located in plasma membrane; 0.4600
analysis: probability located in Golgi body; 0.3700 probability
          located in endoplasmic reticulum (membrane); 0.1000
          probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 53 and 54
analysis:

[0465] A search of the NOV28a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 28C.

TABLE 28C
Geneseq Results for NOV28a
		NOV28a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM79693	Human protein SEQ ID NO 3339 -	3 . . . 223	221/221 (100%)	e−125
	Homo sapiens, 221 aa.	1 . . . 221	221/221 (100%)
	[WO200 157190-A2, 09 AUG. 2001]
AAM78709	Human protein SEQ ID NO 1371 -	1 . . . 202	201/202 (99%)	e−112
	Homo sapiens, 219 aa.	1 . . . 202	201/202 (99%)
	[WO200157190-A2, 09 AUG. 2001]
ABB70928	Drosophila melanogaster polypeptide	12 . . . 192	67/183 (36%)	9e−32
	SEQ ID NO 39576 - Drosophila	8 . . . 186	113/183 (61%)
	melanogaster, 192 aa.
	[WO200171042-A2, 27 SEP. 2001]
ABB93651	Herbicidally active polypeptide SEQ	6 . . . 389	97/407 (23%)	1e−29
	ID NO 2862 - Arabidopsis thaliana,	35 . . . 432	197/407 (47%)
	456 aa. [WO200210210-A2, 07 FEB. 2002]
ABB92691	Herbicidally active polypeptide SEQ	6 . . . 391	108/416 (25%)	4e−29
	ID NO 1902 - Arabidopsis thaliana,	23 . . . 420	198/416 (46%)
	435 aa. [WO200210210-A2, 07 FEB. 2002]

[0466] In a BLAST search of public sequence datbases, the NOV28a protein was found to have homology to the proteins shown in the BLASTP data in Table 28D.

TABLE 28D
Public BLASTP Results for NOV28a
		NOV28a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96C66	Similar to RIKEN cDNA	1 . . . 507	505/507 (99%)	0.0
	1810073N04 gene - Homo sapiens	1 . . . 507	506/507 (99%)
	(Human), 780 aa.
Q9D8J3	1810073N04Rik protein - Mus	1 . . . 377	344/377 (91%)	0.0
	musculus (Mouse), 408 aa.	1 . . . 377	359/377 (94%)
Q99J76	Similar to RIKEN cDNA	1 . . . 364	334/364 (91%)	0.0
	1810073N04 gene - Mus musculus	1 . . . 364	348/364 (94%)
	(Mouse), 375 aa.
Q8SY25	RE05944p - Drosophila	12 . . . 506	158/502 (31%)	5e−73
	melanogaster (Fruit fly), 831 aa.	8 . . . 487	277/502 (54%)
Q8WTK1	Hypothetical 175.6 kDa protein -	128 . . . 440	101/336 (30%)	3e−33
	Caenorhabditis elegans, 1547 aa.	1121 . . . 1451	172/336 (51%)

[0467] PFam analysis predicts that the NOV28a protein contains the domains shown in the Table 28E.

TABLE 28E
Domain Analysis of NOV28a
		Identities/
	NOV28a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
Aa_trans	30 . . . 398	91/476 (19%)	2.1e−13
		256/476 (54%)

Example 29

[0468] The NOV29 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 29A.

TABLE 29A
NOV29 Sequence Analysis
	SEQ ID NO:117	1141 bp
NOV29a,	CCTCTTCAATGGGCAACCTGCTACGGGAAGACCGGGGACCAAGACCTCTGGGTTGGCT
CG124021-01 DNA	TTCCTAGACCCGCTCGGGTCTTCGGGTGTCGCGAGGAAGGGCCCTGCTCCTTTCGTTC
Sequence	CCTGCACCCCTGGCCGCTGCAGGTGGCTCCCTGGAGGAGGAGCTCCCACGCGGAGGAG
	GAGCCAGGGCAGCTGGGAGCGGGGACACCATCCTCCTGGATAAGAGGCAGAGGCCGGG
	AGGAACCCCGTCAGCCGGGCGGGCAGGAAGCTCTGGGAGTAGCCTCATGGAAGAGAAG
	CAGATCCTGTGCGTGGGGCTAGTGGTGCTGGACGTCATCAGCCTGGTGGACAAGTACC
	CTAAGGAGGACTCGGAGATAAGGTGTTTGTCCCAGAGATGGCAGCGCGGAGGCAACGC
	GTCCAACTCCTGCACCATTCTCTCCCTGCTCGGAGCCCCCTGTGCCTTCATGGGCTCA
	ATGGCTCCTGGCCATGTTGCTGAGAGCCTGCCAGATGTGTCTGCTACAGACTTTGAGA
	AGGTTGATCTGACCCAGTTCAAGTGGATCCACATTGAGGGCCGGAACGCATCGGAGCA
	GGTGAAGATGCTGCAGCGGATAGACGCACACAACACCAGGCAGCCTCCAGAGCAGAAG
	ATCCGGGTGTCCGTGGAGGTGGAGAAGCCACGAGAGGAGCTCTTCCAGCTGTTTGGCT
	ACGGAGACGTGGTGTTTGTCAGCAAAGATGTGGCCAAGCACTTGGGGTTCCAGTCAGC
	AGAGGAAGCCTTGAGGGGCTTGTATGGTCGTGTGAGGAAAGGGGCTGTGCTTGTCTGT
	GCCTGGGCTGAGGAGGGCGCCGACGCCCTGGGCCCTGATGGCAAATTGCTCCACTCGG
	ATGCTTTCCCGCCACCCCGCGTGGTGGATACACTGGGAGCTGGAGACACCTTCAATGC
	CTCCGTCATCTTCAGCCTCTCCCAGGGGAGGAGCGTGCAGGAAGCACTGAGATTCGGG
	TGCCAGGTGGCCGGCAAGAAGTGTGGCCTGCAGGGCTTTGATGGCATCGTGTGAGAGC
	AGGTGCCGGCTCCTCACACACCATGGAGACTACCATTGCGGCTGCATCGCCTTCTCCC
	CTCCATCCAGCCTGGCGTCCAGGTTGCCCATTGAAGAGG
	ORF Start: ATG at 279		ORF Stop: TGA at 1038
	SEQ ID NO:118	253 aa	MW at 27590.2 Da
NOV29a,	MEEKQILCVGLVVLDVISLVDKYPKEDSEIRCLSQRWQRGGNASNSCTILSLLGAPCA
CG124021-01	FMGSMAPGHVAESLPDVSATDFEKVDLTQFKWIHIEGRNASEQVKMLQRIDAHNTRQP
Protein Sequence	PEQKIRVSVEVEKPREELFQLFGYGDVVFVSKDVAKHLGFQSAEEALRGLYGRVRKGA
	VLVCAWAEEGADALGPDGKLLHSDAFPPPRVVDTLGAGDTFNASVIFSLSQGRSVQEA
	LRFGCQVAGKKCGLQGFDGIV
	SEQ ID NO:119	947 bp
NOV29b,	TTAGCCTCATGGAAGAGAAGCAGATCCTGTGCGTGGGGGTAGTGGTGCTGGACGTCAT
CG124021-02 DNA	CAGCCTGGTGGACAAGTACCCTAAGGAGGACTCGGAGATAAGGTGTTTGTCCCAGAGA
Sequence	TGGCAGCGCGGAGGCAACGCGTCCAACTCCTGCACCGTTCTCTCCCTGCTCGGAGCCC
	CCTGTGCCTTCATGGGCTCAATGGCTCCTGGCCATGTTGCTGACTTCCTGGTGGCCGA
	CTTCAGGCGGCGGGGCGTGGACGTGTCTCAGGTGGCCTGGCAGAGCAAGGGGGACACC
	CCCAGCTCCTGCTGCATCATCAACAACTCCAATGGCAACCGTACCATTGTGCTCCATG
	ACACGAGCCTGCCAGATGTGTCTGCTACAGACTTTGAGAAGGTTCATCTGACCCAGTT
	CAAGTGGATCCACATTGAGGGCCGGAACGCATCGGAGCAGGTGAAGATGCTGCAGCGG
	ATAGACGCACACAACACCAGGCAGCCTCCAGAGCAGAAGATCCGGGTGTCCGTGGAGG
	TGGAGAAGCCACGAGAGGAGCTCTTCCAGCTGTTTGGCTACGGAGACGTGGTGTTTGT
	CAGCAAAGATGTGGCCAAGCACTTGGGGTTCCAGTCAGCAGAGGAAGCCTTGAGGGGC
	TTGTATGGTCGTGTGAGGAAAGGGGCTGTGCTTGTCTGTGCCTGGGCTGAGGAGGGCG
	CCGACGCCCTGGGCCCTGATGGCAAATTGCTCCACTCGGATGCTTTCCCGCCACCCCG
	CGTGGTGGATACACTGGGAGCTGGAGACACCTTCAATGCCTCCGTCATCTTCAGCCTC
	TCCCAGGGGAGGAGCGTGCAGGAAGCACTGAGATTCGGGTGCCAGGTGGCCGGCAAGA
	AGTGTGGCCTGCAGGGCTTTGATGGCATCGTGTGAGAGCAGGTGCCGGCTCCTCACAC
	ACCATGGAGACTACCATTG
	ORF Start: ATG at 9		ORF Stop: TGA at 903
	SEQ ID NO:120	298 aa	MW at 32522.7 Da
NOV29b,	MEEKQILCVGLVVLDVISLVDKYPKEDSEIRCLSQRWQRGGNASNSCTVLSLLGAPCA
CG124021-02	FMGSMAPGHVADFLVADFRRRGVDVSQVAWQSKGDTPSSCCIINNSNGNRTIVLHDTS
Protein Sequence	LPDVSATDFEKVDLTQFKWIHIEGRNASEQVKMLQRIDAHNTRQPPEQKIRVSVEVEK
	PREELFQLFGYGDVVFVSKDVAKHLGFQSAEEALRGLYGRVRKGAVLVCAWAEEGADA
	LGPDGKLLHSDAFPPPRVVDTLGAGDTFNASVIFSLSQGRSVQEALRFGCQVAGKKCG
	LQGFDGIV
	SEQ ID NO:121	1149 bp
NOV29c,	AGGCAGAGGCCGGGAGGAACCCCGTCAGCCGGGCGGGCAGGAAGCTCTGGGAGTAGCC
CG124021-04 DNA	TCATGGAAGAGAAGCAGATCCTGTGCGTGGGGCTAGTGGTGCTGGACGTCATCAGCCT
Sequence	GGTGGACAAGTACCCTAAGGAGGACTCGGAGATAAGGTGTTTGTCCCAGAGATGGCAG
	CGCGGAGGCAACGCGTCCAACTCCTGCACCGTTCTCTCCCTGCTCGGAGCCCCCTGTG
	CCTTCATGGGCTCAATGGCTCCTGGCCATGTTGCTGATTTTGTCCTGGATGACCTCCG
	CCGCTATTCTGTGGACCTACGCTACACAGTCTTTCAGACCACAGGCTCCGTCCCCATC
	GCCACGGTCATCATCAACGAGGCCAGTGGTAGCCGCACCATCCTATACTATGACAGCT
	TCCTGGTGGCCGACTTCAGGCGGCGGGGCGTGGACGTGTCTCAGGTGGCCTGGCAGAG
	CAAGGGGGACACCCCCAGCTCCTGCTGCATCATCAACAACTCCAATGGCAACCGTACC
	ATTGTGCTCCATGACACGAGCCTGCCAGATGTGTCTGCTACAGACTTTGAGAAGGTTG
	ATCTGACCCAGTTCAAGTGGATCCACATTGAGGGCCGGAACGCATCGGAGCAGGTGAA
	GATGCTGCAGCGGATAGACGCACACAACACCAGGCAGCCTCCAGAGCAGAAGATCCGG
	GTGTCCGTGGAGGTGGAGAAGCCACGAGAGGAGCTCTTCCAGCTGTTTGGCTACGGAG
	ACGTGGTGTTTGTCAGCAAAGATGTGGCCAAGCACTTGGGGTTCCAGTCAGCAGAGGA
	AGCCTTGAGGGGCTTGTATGGTCGTGTGAGGAAAGGGGCTGTGCTTGTCTGTGCCTGG
	GCTGAGGAGGGCGCCGACGCCCTGGGCCCTGATGGCAAATTGCTCCACTCGGATGCTT
	TCCCGCCACCCCGCGTGGTGGATACACTGGGAGCTGGAGACACCTTCAATGCCTCCGT
	CATCTTCAGCCTCTCCCAGGGGAGGAGCGTGCAGGAAGCACTGAGATTCGGGTGCCAG
	GTGGCCGGCAAGAAGTGTGGCCTGCAGGGCTTTGATGGCATCGTGTGAGAGCAGGTGC
	CGGCTCCTCACACACCATGGAGACTACCATTGCGGCTGCATCGCCTT
	ORF Start: ATG at 61		ORF Stop: TGA at 1090
	SEQ ID NO:122	343 aa	MW at 37621.3 Da
NOV29c,	MEEKQILCVGLVVLDVISLVDKYPKEDSEIRCLSQRWQRGGNASNSCTVLSLLGAPCA
CG124021-04	FMGSMAPGHVADFVLDDLRRYSVDLRYTVFQTTGSVPIATVIINEASGSRTILYYDSF
Protein Sequence	LVADFRRRGVDVSQVAWQSKGDTPSSCCIINNSNGNRTIVLHDTSLPDVSATDFEKVD
	LTQFKWIHIEGRNASEQVKMLQRIDAHNTRQPPEQKIRVSVEVEKPREELFQLFGYGD
	VVFVSKDVAKHLGFQSAEEALRGLYGRVRKGAVLVCAWAEEGADALGPDGKLLHSDAF
	PPPRVVDTLGAGDTFNASVIFSLSQGRSVQEALRFGCQVAGKKCGLQGFDGIV

[0469] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 29B.

TABLE 29B
Comparison of NOV29a against NOV29b and NOV29c.
Protein	NOV29a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV29b	1 . . . 253	251/298 (84%)
	1 . . . 298	253/298 (84%)
NOV29c	71 . . . 253	183/183 (100%)
	161 . . . 343	183/183 (100%)

[0470] Further analysis of the NOV29a protein yielded the following properties shown in Table 29C.

TABLE 29C
Protein Sequence Properties NOV29a
PSort     0.8048 probability located in outside;
analysis: 0.1900 probability located in lysosome (lumen); 0.1000
          probability located in endoplasmic reticulum (membrane);
          0.1000 probability located in endoplasmic reticulum (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0471] A search of the NOV29a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 29D.

TABLE 29D
Geneseq Results for NOV29a
		NOV29a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB71549	Drosophila melanogaster polypepetide	4 . . . 252	92/297 (30%)	3e−35
	SEQ ID NO 41439 - Drosophila	5. . . 299	142/297 (46%)
	melanogaster, 306 aa.
	[WO200171042-A2, 27 SEP. 2001]
ABB63356	Drosophila melanogaster polypeptide	3 . . . 248	82/264 (31%)	8e−27
	SEQ ID NO 16860 - Drosophila	14 . . . 267	132/264 (49%)
	melanogaster, 275 aa.
	[WO200171042-A2, 27 SEP. 2001]
ABB62122	Drosophila melanogaster polypeptide	4 . . . 250	82/300 (27%)	4e−24
	SEQ ID NO 13158 - Drosophila	2 . . . 300	131/300 (43%)
	melanogaster, 369 aa.
	[WO200171042-A2, 27 SEP. 2001]
AAB96127	Putative P. abyssi ribokinase -	6 . . . 240	63/259 (24%)	4e−06
	Pyrococcus abyssi, 293 aa.	5 . . . 261	106/259 (40%)
	[FR2792651-A1, 27 OCT. 2000]
ABB52478	Escherichia coli polypeptide SEQ ID	5 . . . 248	63/283 (22%)	1e−05
	NO 299 - Escherichia coli, 298 aa.	3 . . . 279	110/283 (38%)
	[WO200166572-A2, 13 SEP. 2001]

[0472] In a BLAST search of public sequence datbases, the NOV29a protein was found to have homology to the proteins shown in the BLASTP data in Table 29E.

TABLE 29E
Public BLASTP Results for NOV29a
		NOV29a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P50053	Ketohexokinase (EC 2.7.1.3)	1 . . . 253	251/298 (84%)	e−138
	(Hepatic fructokinase) - Homo	1 . . . 298	253/298 (84%)
	sapiens (Human), 298 aa.
Q91WU8	Ketohexokinase - Mus musculus	1 . . . 253	221/298 (74%)	e−123
	(Mouse), 298 aa.	1 . . . 298	241/298 (80%)
P97328	Ketohexokinase (BC 2.7.1.3)	1 . . . 253	220/298 (73%)	e−122
	(Hepatic fructokinase) - Mus	1 . . . 298	240/298 (79%)
	musculus (Mouse), 298 aa.
Q02974	Ketohexokinase (EC 2.7.1.3)	1 . . . 253	217/298 (72%)	e−121
	(Hepatic fructokinase) - Rattus	1 . . . 298	241/298 (80%)
	norvegicus (Rat), 298 aa.
Q9CPP1	Ketohexokinase - Mus musculus	102 . . . 253	134/152 (88%)	6e−74
	(Mouse), 152 aa (fragment).	1 . . . 152	143/152 (93%)

[0473] PFam analysis predicts that the NOV29a protein contains the domains shown in the Table 29F.

TABLE 29F
Domain Analysis of NOV29a
		Identities/
	NOV29a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
pfkB	3 . . . 253	64/327 (20%)	1.1e−24
		180/327 (55%)

Example 30

[0474] The NOV30 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 30A.

TABLE 30A
NOV30 Sequence Analysis
	SEQ ID NO:123	1477 bp
NOV30a,	GAGAGCAATCACTCCCGGCTGCTTTTCACCTCTGACAGAGCCCAGACACCATGAACGC
CG150245-01 DNA	AAGTGAATTCCGAAGGAGAGGGAAGGAGATGGTGGATTACGTGGCCAACTACATGGAA
Sequence	GGCATTGAGGGACGCCAGGTCTACCCTGACGTGGAGCCCGGGTACCTGCGGCCGCTGA
	TCCCTGCCGCTGCCCCTCAGGAGCCAGACACGTTTGAGGACATCATCAACGACGTTGA
	GAAGATAATCATGCCTGGGGCGGCAAGCCCAGCATGCACAGAGCTGGAGACTGTGATG
	ATGGACTGGCTCGGGAAGATGCTGGAACTACCAAAGGCATTTTTGAATGAGAAAGCTG
	GAGAAGGGGGAGGAGTGATCCAGGGAAGTGCCAGTGAAGCCACCCTGGTGGCCCTGCT
	GGCCGCTCGGACCAAAGTGATCCATCGGCTGCAGGCAGCGTCCCCAGAGCTCACACAG
	GCCGCTATCATGGAGAAGCTGGTGGCTTACTCATCCGATCAGGCACACTCCTCAGTGG
	AAAGAGCTGGGTTAATTGGTGGAGTGAAATTAAAAGCCATCCCCTCAGATGGCAACTT
	CGCCATGCGTGCGTCTGCCCTGCAGGAAGCCCTGGAGAGAGACAAAGCGGCTGGCCTG
	ATTCCTTTCTTTATGGTTGCCACCCTGGGGACCACAACATGCTGCTCCTTTGACAATC
	TCTTAGAAGTCGGTCCTATCTGCAACAAGGAAGACATATGGCTGCACGTTGATGCAGC
	CTACGCAGGCAGTGCATTCATCTGCCCTGAGTTCCGGCACCTTCTGAATGGAGTGGAG
	TTTGCAGATTCATTCAACTTTAATCCCCACAAATGGCTATTGGTGAATTTTGACTGTT
	CTGCCATGTGGGTGAAAAAGAGAACAAACTTAACGGGAGCCTTTAGACTGGACCCCAC
	TTACCTGAAGCACAGCCATCAGGATTCAGGGCTTATCACTGACTACCGGCATTGGCAG
	ATACCACTGGGCAGAAGATTTCGCTCTTTGAAAATGTGGTTTGTATTTAGGATGTATG
	GAGTCAAAGGACTGCAGGCTTATATCCGCAAGCATGTCCAGCTGTCCCATGAGTTTGA
	GTCACTGGTGCGCCAGGATCCCCGCTTTGAAATCTGTGTGGAAGTCATTCTGGGGCTT
	GTCTGCTTTCGGCTAAAGGGTTCCAACAAAGTGAATGAAGCTCTTCTGCAAAGAATAA
	ACAGTGCCAAAAAAATCCACTTGGTTCCATGTCACCTCAGGGACAAGTTTGTCCTGCG
	CTTTGCCATCTGTTCTCGCACGGTGGAATCTGCCCATGTGCAGCGGGCCTGGGAACAC
	ATCAAAGAGCTGGCGGCCGACGTGCTGCGAGCAGAGAGGGAGTAGGAGTGAAGCCAGC
	TGCAGGAATCAAAAATTGAAGAGAGATATATCTGAAAACTGGAATAAGAAGCAAATAA
	ATATCATCCTGCCTTCATGGAACTCAG
	ORF Start: ATG at 51		ORF Stop: TAG at 1377
	SEQ ID NO:124	442 aa	MW at 49663.8 Da
NOV30a,	MNASEFRRRGKEMVDYVANYMEGIEGRQVYPDVEPGYLRPLIPAAAPQEPDTFEDIIN
CG150245-01	DVEKIIMPGAASPACTELETVMMDWLGKMLELPKAFLNEKAGEGGGVIQGSASEATLV
Protein Sequence	ALLAARTKVIHRLQAASPELTQAAIMEKLVAYSSDQAHSSVERAGLIGGVKLKAIPSD
	GNFAMRASALQEALERDKAAGLIPFFMVATLGTTTCCSFDNLLEVGPICNKEDIWLHV
	DAAYAGSAFICPEFRHLLNGVEFADSFNFNPHKWLLVNFDCSAMWVKKRTNLTGAFRL
	DPTYLKHSHQDSGLITDYRHWQIPLGRRFRSLKMWFVFRMYGVKGLQAYIRKHVQLSH
	EFESLVRQDPRFEICVEVILGLVCFRLKGSNKVNEALLQRINSAKKIHLVPCHLRDKF
	VLRFAICSRTVESAHVQRAWEHIKELAADVLRAERE
	SEQ ID NO:125	1803 bp
NOV30b,	GAGAGCAATCACTCCCGGCTGCTTTTCACCTCTGACAGAGCCCAGACACCATGAACGC
CG150245-02 DNA	AAGTGAATTCCGAAGGAGAGGGAAGGAGATGGTGGATTACGTGGCCAACTACATGGAA
Sequence	GGCATTGAGGGACGCCAGGTCTACCCTGACGTGGAGCCCGGGTACCTGCGGCCGCTGA
	TCCCTGCCGCTGCCCCTCAGGAGCCAGACACGTTTGAGGACATCATCAACGACGTTGA
	GAAGATAATCATGCCTGGGGCGGCAAGCCCAGCATGCACAGAGCTGGAGACTGTGATG
	ATGGACTGGCTCGGGAAGATGCTGGAACTACCAAAGGCATTTTTGAATGAGAAAGCTG
	GAGAAGGGGGAGGAGTGATCCAGGGAAGTGCCAGTGAAGCCACCCTGGTGGCCCTGCT
	GGCCGCTCGGACCAAAGTGATCCATCGGCTGCAGGCAGCGTCCCCAGAGCTCACACAG
	GCCGCTATCATGGAGAAGCTGGTGGCTTACTCATCCGATCAGGCACACTCCTCAGTGG
	AAAGAGCTGGGTTAATTGGTGGAGTGAAATTAAAAGCCATCCCCTCAGATGGCAACTT
	CGCCATGCGTGCGTCTGCCCTGCAGGAAGCCCTGGAGAGAGACAAAGCGGCTGGCCTG
	ATTCCTTTCTTTATGGTTGCCACCCTGGGGACCACAACATGCTGCTCCTTTGACAATC
	TCTTAGAAGTCGGTCCTATCTGCAACAAGGAAGACATATGGCTGCACGTTGATGCAGC
	CTACGCAGGCAGTGCATTCATCTGCCCTGAGTTCCGGCACCTTCTGAATGGACTGGAG
	TTTGCAGATTCATTCAACTTTAATCCCCACAAATGGCTATTGGTGAATTTTGACTGTT
	CTGCCATGTGGGTGAAAAAGAGAACAGACTTAACGGGAGCCTTTAGACTGGACCCCAC
	TTACCTGAAGCACAGCCATCAGGATTCAGGGCTTATCACTGACTACCGGCATTGGCAG
	ATACCACTGGGCAGAAGATTTCGCTCTTTGAAAATGTGGTTTGTATTTAGGATGTATG
	GAGTCAAAGGACTGCAGGCTTATATCCGCAAGCATGTCCAGCTGTCCCATGAGTTTGA
	GTCACTGGTGCGCCAGGATCCCCGCTTTGAAATCTGTGTGGAAGTCATTCTGGGGCTT
	GTCTGCTTTCGGCTAAAGGGTTCCAACAAAGTGAATGAAGCTCTTCTGCAAAGAATAA
	ACAGTGCCAAAAAAATCCACTTGGTTCCATGTCACCTCAGGGACAAGTTTGTCCTGCG
	CTTTGCCATCTGTTCTCGCACGGTGGAATCTGCCCATGTGCAGCGGGCCTGGGAACAC
	ATCAAAGAGCTGGCGGCCGACGTGCTGCGAGCAGAGAGGGAGTAGGAGTGAAGCCAGC
	TGCAGGAATCAAAAATTGAAGAGAGATATATCTGAAAACTGGAATAAGAAGCAAATAA
	ATATCATCCTGCCTTCATGGAACTCAGCTGTCTGTGGCTTCCCATGTCTTTCTCCAAA
	GTTATCCAGAGGGTTGTGATTTTGTCTGCTTAGTATCTCATCAACAAAGAAATATTAT
	TTGCTAATTAAAAAGTTAATCTTCATGGCCATAGCTTTTATTCATTAGCTGTGATTTT
	TGTTGATTAAAACATTATAGATTTTCATGTTCTTGCAGTCATCAGAAGTGGTAGGAAA
	GCCTCACTGATATATTTTCCAGGGCAATCAATGTTCACGCAACTTGAAATTATATCTG
	TGGTCTTCAAATTGTCTTTTGTCATGTGGCTAAATGCCTAATAAACAATTCAAGTGAA
	ATACT
	ORF Start: ATG at 51		ORF Stop: TAG at 1377
	SEQ ID NO:126	442 aa	MW at 49664.8 Da
NOV30b,	MNASEFRRRGKEMVDYVANYMEGIEGRQVYPDVEPGYLRPLIPAAAPQEPDTFEDIIN
CG150245-02	DVEKIIMPGAASPACTELETVMMDWLGKMLELPKAFLNEKAGEGGGVIQGSASEATLV
Protein Sequence	ALLAARTKVIHRLQAASPELTQAAIMEKLVAYSSDQAHSSVERAGLIGGVKLKAIPSD
	GNFAMRASALQEALERDKAAGLIPFFMVATLGTTTCCSFDNLLEVGPICNKEDIWLHV
	DAAYAGSAFICPEFRHLLNGVEFADSFNFNPHKWLLVNFDCSAMWVKKRTDLTGAFRL
	DPTYLKHSHQDSGLITDYRHWQIPLGRRFRSLKMWFVFRMYGVKGLQAYIRKHVQLSH
	EFESLVRQDPRFEICVEVILGLVCFRLKGSNKVNEALLQRINSAKKIHLVPCHLRDKF
	VLRFAICSRTVESAHVQRAWEHIKELAADVLRAERE

[0475] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 30B.

TABLE 30B
Comparison of NOV30a against NOV30b.
Protein	NOV3a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV30b	1 . . . 442	441/442 (99%)
	1 . . . 442	442/442 (99%)

[0476] Further analysis of the NOV30a protein yielded the following properties shown in Table 30C.

TABLE 30C
Protein Sequence Properties NOV30a
PSort     0.4500 probability located in cytoplasm; 0.1938 probability
analysis: located in microbody (peroxisome); 0.1607 probability located
          in lysosome (lumen); 0.1000 probability located in
          mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0477] A search of the NOV30a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 30D.

TABLE 30D
Geneseq Results for NOV30a
		NOV30a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAG63571	Amino acid sequence of a L-aromatic	1 . . . 440	386/478 (80%)	0.0
	amino acid decarboxylase - Sus	1 . . . 478	418/478 (86%)
	scrofa, 486 aa. [WO200155342-A2,
	02 AUG. 2001]
AAG63572	Synthetic amino acid sequence of L-	2 . . . 440	385/477 (80%)	0.0
	aromatic amino acid decarboxylase -	3 . . . 479	417/477 (86%)
	Synthetic, 487 aa. [WO200155342-
	A2, 02 AUG. 2001]
ABB72012	Drosophila melanogaster polypeptide	1 . . . 441	260/479 (54%)	e−149
	SEQ ID NO 42828 - Drosophila	36 . . . 510	335/479 (69%)
	melanogaster, 510 aa.
	[WO200171042-A2, 27 SEP. 2001]
ABB72010	Drosophila melanogaster polypeptide	1 . . . 441	260/479 (54%)	e−149
	SEQ ID NO 42822 - Drosophila	1 . . . 475	335/479 (69%)
	melanogaster, 475 aa.
	[WO200171042-A2, 27 SEP. 2001]
ABB66348	Drosophila melanogaster polypeptide	1 . . . 441	260/479 (54%)	e−149
	SEQ ID NO 25836 - Drosophila	1 . . . 475	335/479 (69%)
	melanogaster, 475 aa.
	[WO200171042-A2, 27 SEP. 2001]

[0478] In a BLAST search of public sequence datbases, the NOV30a protein was found to have homology to the proteins shown in the BLASTP data in Table 30E.

TABLE 30E
Public BLASTP Results for NOV30a
		NOV30a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P20711	Aromatic-L-amino-acid	1 . . . 442	441/480 (91%)	0.0
	decarboxylase (EC 4.1.1.28) (AADC)	1 . . . 480	442/480 (91%)
	(DOPA decarboxylase) (DDC) -
	Homo sapiens (Human), 480 aa.
O88533	Aromatic-L-amino-acid	1 . . . 442	390/480 (81%)	0.0
	decarboxylase (EC 4.1.1.28) (AADC)	1 . . . 480	424/480 (88%)
	(DOPA decarboxylase) (DDC) - Mus
	musculus (Mouse), 480 aa.
P14173	Aromatic-L-amino-acid	1 . . . 442	386/480 (80%)	0.0
	decarboxylase (EC 4.1.1.28) (AADC)	1 . . . 480	423/480 (87%)
	(DOPA decarboxylase) (DDC) -
	Rattus norvegicus (Rat), 480 aa.
Q62819	Aromatic L-amino acid decarboxylase -	1 . . . 437	381/475 (80%)	0.0
	Rattus norvegicus (Rat), 483 aa.	1 . . . 475	417/475 (87%)
P22781	Aromatic-L-amino-acid	1 . . . 441	382/479 (79%)	0.0
	decarboxylase (EC 4.1.1.28) (AADC)	1 . . . 479	418/479 (86%)
	(DOPA decarboxylase) (DDC) -
	Cavia porcellus (Guinea pig), 480 aa.

[0479] PFam analysis predicts that the NOV30a protein contains the domains shown in the Table 30F.

TABLE 30F
Domain Analysis of NOV30a
		Identities/
	NOV30a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
pyridoxal_deC	35 . . . 67	21/33 (64%)	4.7e−13
		32/33 (97%)
pyridoxal_deC	68 . . . 376	192/327 (59%)	6.6e−193
		297/327 (91%)

Example 31

[0480] The NOV31 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 31A.

TABLE 31A
NOV31 Sequence Analysis
	SEQ ID NO: 127	1171 bp
NOV31a,	GTCGCCAGCCGAGCCACATCGCTCAGAACACCTATGGGGAAGGTGAAGGTCGGAGTCA
CG55814-02 DNA
Sequence	ACGGATTTGGTCGTATTGGGCGCCTGGTCACCAGGGCTGCTTTTAACTCTGGTAAAGT
	GGATATTGTTGCCATCAATGACCCCTTCATTGACCTCAACTACATGGTTTACATGTTC
	CAATATGATTCCACCCATGGCAAATTCCATGGCACCGTCAAGGCTGAGAACGGGAAGC
	TTGTGATCAATGGAAATCCCATCACCATCTTCCAGGAGCGAGATCCCTCCAAAATCAA
	GTGGGGCGATGCTGGCGCTGAGTACGTCGTGGAGTCCACTGGCGTCTTCACCACCATG
	GAGAAGGCTGGGGCTCATTTGCAGGGGGGAGCCAAAAGGGTCATCATCTCTGCCCCCT
	CTGCTGATGCCCCCATGTTCGTCATGGGTGTGAACCATGAGAAGTATGACAACAGCCT
	CAAGATCATCAGCAATGCCTCCTGCACCACCAACTGCTTAGCACCCCTGGCCAAGGTC
	ATCCATGACAACTTTGGTATCGTGGAAGGACTCATGACCACAGTCCATGCCATCACTG
	CCACCCAGAAGACTGTGGATGGCCCCTCCGGGAAACTGTGGCGTGATGGCCGCGGGGC
	TCTCCAGAAGCTCACTGGCATGGCCTTCCGTGTCCCCACTGCCAACGTGTCAGTGGTG
	GACCTGACCTGCCGTCTAGAAAAACCTGCCAAATATGATGACATCAAGAAGGTGGTGA
	AGCAGGCGTCGGAGGGCCCCCTCAAGGGCATCCTGGGCTACACTGAGCACCAGGTGGT
	CTCCTCTGACTTCAACAGCGACACCCACTCCTCCACCTTTGACGCTGGGGCTGGCATT
	GCCCTCAACGACCACTTTGTCAAGCTCATTTCCTGGTATGACAACGAATTTGGCTACA
	GCAACAGGGTGGTGGACCTCATGGCCCACATGGCCTCCAAGGAGTAAGACCCCTGGAC
	CACCAGCCCCAGCAAGAGCACAAGAGGAAGAGAGAGACCCTCACTGCTGGGGAGTCCC
	TGCCACACTCAGTCCCCCACCACACTGAATCTCCCCTCCTCACAGTTGCCATGTAGAC
	CCTTGAAGAGGGGAGGGGCCTAGGGCGCCGCACCTTGTCATGTACCTCAATAAAGTAC
	CTGGGCTTACC
	ORF Start: ATG at 34	ORF Stop: TAA at 973
	SEQ ID NO: 128	313 aa	MW at 33950.5Da
NOV31a,	MGKVKVGVNGFGRIGRLVTRAAFNSGKVDIVAINDPFIDLNYMVYMFQYDSTHGKFHG
CG55814-02
Protein Sequence	TVKAENGKLVINGNPITIFQERDPSKIKWGDAGAEYVVESTGVFTTMEKAGAHLQGGA
	KRVIISAPSADAPMFVMGVNHEKYDNSLKIISNASCTTNCLAPLAKVIHDNFGIVEGL
	MTTVHAITATQKTVDGPSGKLWRDGRGALQKLTGMAFRVPTANVSVVDLTCRLEKPAK
	YDDIKKVVKQASEGPLKGILGYTEHQVVSSDFNSDTHSSTFDAGAGIALNDHFVKLIS
	WYDNEFGYSNRVVDLMAHMASKE

[0481] Further analysis of the NOV31a protein yielded the following properties shown in Table 31B.

TABLE 31B
Protein Sequence Properties NOV31a
PSort     0.5181 probability located in microbody (peroxisome);
analysis: 0.4500 probability located in cytoplasm; 0.1977 probability
          located in lysosome (lumen); 0.1000 probability located in
          mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0482] A search of the NOV31a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 31C.

TABLE 31C
Geneseq Results for NOV31a
		NOV31a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAY05368	Human HCMV inducible gene	1 . . . 313	313/335 (93%)	e−179
	protein, SEQ ID NO 4 - Homo	1 . . . 335	313/335 (93%)
	sapiens, 335 aa. [WO9913075-A2,
	18 MAR. 1999]
AAY07036	Breast cancer associated antigen	1 . . . 313	313/335 (93%)	e−179
	precursor sequence - Homo sapiens,	1 . . . 335	313/335 (93%)
	335 aa. [WO9904265-A2, 28 JAN. 1999]
ABG13650	Novel human diagnostic protein	1 . . . 313	310/335 (92%)	e−177
	#13641 - Homo sapiens, 357 aa.	23 . . . 357	310/335 (92%)
	[WO200175067-A2, 11 OCT. 2001]
ABG13646	Novel human diagnostic protein	1 . . . 313	310/335 (92%)	e−177
	#13637 - Homo sapiens, 357 aa.	23 . . . 357	310/335 (92%)
	[WO200175067-A2, 11 OCT. 2001]
ABG13650	Novel human diagnostic protein	1 . . . 313	310/335 (92%)	e−177
	#13641 - Homo sapiens, 357 aa.	23 . . . 357	310/335 (92%)
	[WO200175067-A2, 11 OCT. 2001]

[0483] In a BLAST search of public sequence datbases, the NOV31a protein was found to have homology to the proteins shown in the BLASTP data in Table 31D.

TABLE 31D
Public BLASTP Results for NOV31a
		NOV31a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
BAB93466	Glyceraldehype-3-phosphate	1 . . . 313	313/335 (93%)	e−178
	dehydrogenase - Homo sapiens	1 . . . 335	313/335 (93%)
	(Human), 335 aa.
P04406	Glyceraldehyde 3-phosphate	2 . . . 313	312/334 (93%)	e−178
	dehydrogenase, liver (EC 1.2.1.12) -	1 . . . 334	312/334 (93%)
	Homo sapiens (Human), 334 aa.
Q9N2D5	Glyceraldehyde−3-phosphate	4 . . . 313	299/332 (90%)	e−170
	dehydrogenase - Felis silvestris	2 . . . 333	303/332 (91%)
	catus (Cat), 333 aa.
P00355	Glyceraldehyde 3-phosphate	4 . . . 313	296/332 (89%)	e−168
	dehydrogenase (EC 1.2.1.12)	1 . . . 332	301/332 (90%)
	(GAPDH) - Sus scrofa (Pig), 332
	aa.
Q9N2D6	Glyceraldehyde−3-phosphate	4 . . . 313	294/332 (88%)	e−167
	dehydrogenase - Canis familiaris	2 . . . 333	301/332 (90%)
	(Dog), 333 aa.

[0484] PFam analysis predicts that the NOV31a protein contains the domains shown in the Table 31E.

TABLE 31E
Domain Analysis of NOV31a
		Identities/
	NOV31a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
gpdh	3 . . . 152	95/180 (53%)	3.1e−144
		143/180 (79%)
gpdh_C	153 . . . 204	40/55(73%)	1.1e−33
		48/55 (87%)
gpdh_C	205 . . . 292	61/99 (62%)	le−53
		86/99 (87%)

Example 32

[0485] The NOV32 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 32A.

TABLE 32A
NOV32 Sequence Analysis
	SEQ ID NO: 129	3555 bp
NOV32a,	TGCGGCCGCGGAAAGAATGCGCGCCGCCCGTGCGCTCCGCCTGCCGCGTCTGGCCACC
CG56735-
01 DNA	CGCAGCCGCCGCGTCCGCACCTGACCATGGAGTGCGCCCTCCTGCTCGCGTGTGCCTT
Sequence
	CCCGGCTGCGGGTTCGGGCCCGCCGAGGGGCCTGGCGGGACTGGGGCGCGTGGCCAAG
	GCGCTCCAGCTGTGCTGCCTCTGCTGTGCGTCGGTCGCCGCGGCCTTAGCCAGTGACA
	GCAGCAGCGGCGCCAGCGGATTAAATGATGATTACGTCTTTGTCACGCCAGTAGAAGT
	AGACTCAGCCGGGTCATATATTTCACACGACATTTTGCACAACGGCAGGAAAAAGCGA
	TCGGCGCAGAATGCCAGAAGCTCCCTGCACTACCGATTTTCAGCATTTGGACAGGAAC
	TGCACTTAGAACTTAAGCCCTCGGCGATTTTGAGCAGTCACTTTATTGTCCAGGTACT
	TGGAAAAGATGGTGCTTCAGAGACTCAGAAACCCGAGGTGCAGCAATGCTTCTATCAG
	GAATTTATCAGAAATGACAGCTCCTCCTCTGTCGCTGTGTCTACGTGTGCTGGCTTGT
	CAGGTTTAATAAGGACACGAAAAAATGAATTCCTCATCTCGCCATTACCTCAGCTTCT
	GGCCCAGGAACACAACTACAGCTCCCCTGCGGGTCACCATCCTCACGTACTGTACAAA
	AGGACAGCAGAGGAGAAGATCCAGCGGTACCGTGGCTACCCCGGCTCTGGCCGGAATT
	ATCCTGGTTACTCCCCAAGTCACATTCCCCATGCATCTCAGAGTCGAGAGACAGAGTA
	TCACCATCGAAGGTTGCAAAAGCAGCATTTTTGTGGACGACGCAAGAAATATGCTCCC
	AAGCCTCCCACAGAGGACACCTATCTAAGGTTTGATGAATATGGGAGCTCTGGGCGAC
	CCAGAAGATCAGCTGGAAAATCACAAAAGGGCCTCAATGTGGAAACCCTCGTGGTGGC
	AGACAAGAAAATGGTGGAAAAGCATGGCAAGGGAAATGTCACCACATACATTCTCACA
	GTAATGAACATGGTTTCTGGCCTATTTAAAGATGGGACTATTGGAAGTGACATAAACG
	TGGTTGTGGTGAGCCTAATTCTTCTGGAACAAGAACCTGGAGGATTATTGATCAACCA
	TCATGCAGACCAGTCTCTGAATAGTTTTTGTCAATGGCAGTCTGCCCTCATTGGAAAG
	AATGGCAAGAGACATGATCATGCCATCTTACTAACAGGATTTGATATTTGTTCTTGGA
	AGAATGAACCATGTGACACTCTAGGGTTTGCCCCCATCAGTGGAATGTGCTCTAAGTA
	CCGAAGTTGTACCATCAATGAGGACACAGGACTTGGCCTTGCCTTCACCATCGCTCAT
	GAGTCAGGGCACAACTTTGGTATGATTCACGACGGAGAAGGGAATCCCTGCAGAAAGG
	CTGAAGGCAATATCATGTCTCCCACACTGACCGGAAACAATGGAGTGTTTTCATGGTC
	TTCCTGCAGCCGCCAGTATCTCAAGAAATTCCTCAGCACACCTCAGGCGGGGTGTCTA
	GTGGATGAGCCCAAGCAAGCAGGACAGTATAAATATCCGGACAAACTACCAGGACAGA
	TTTATGATGCTGACACACAGTGTAAATGGCAATTTGGAGCAAAAGCCAAGTTATGCAG
	CCTTGGTTTTGTGAAGGATATTTGCAAATCACTTTGGTGCCACCGAGTAGGCCACAGG
	TGTGAGACCAAGTTTATGCCCGCAGCAGAAGGGACCGTTTGTGGCTTGAGTATGGTAA
	ACTGCATACTTTGGTGTCGGCAAGGCCAGTGCGTAAAGTTTGGGGAGCTCGGGCCCCG
	GCCCATCCACGGCCAGTGGTCCGCCTGGTCGAAGTCGTCAGAATGTTCCCGGACATGT
	GGTGGAGGAGTCAAGTTCCAGGAGAGACACTGCAATAACCCCAAGCCTCAGTATGGTG
	GCTTATTCTGTCCAGGTTCTAGCCGTATTTATCAGCTGTGCAATATTAACCCTTGCAA
	TGAAAATAGCTTGGATTTTCGGGCTCAACAGTGTGCAGAATATAACAGCAAACCTTTC
	CGTGGATGGTTCTACCAGTGGAAACCCTATACAAAAGTGGAAGAGGAAGATCGATGCA
	AACTGTACTGCAAGGCTGAGAACTTTGAATTTTTTTTTGCAATGTCCGGCAAAGTGAA
	AGATGGAACTCCCTGCTCCCCAAACAAAAATGATGTTTGTATTGACGGGGTTTGTGAA
	CTAGTGGGATGTGATCATGAACTAGGCTCTAAAGCAGTTTCAGATGCTTGTGGCGTTT
	GCAAAGGTGATAATTCAACTTGCAAGTTTTATAAAGGCCTGTACCTCAACCAGCATAA
	AGCAAATGAATATTATCCGGTGGTCCTCATTCCAGCTGGCGCCCGAAGCATCGAAATC
	CAGGAGCTGCAGGTTTCCTCCAGTTACCTCGCAGTTCGAAGCCTCAGTCAAAAGTATT
	ACCTCACCGGGGGCTGGAGCATCGACTGGCCTGGGGAGTTCCCCTTCGCTGGGACCAC
	GTTTGAATACCAGCGCTCTTTCAACCGCCCGGAACGTCTGTACGCGCCAGGGCCCACA
	AATGAGACGCTGGTCTTTGAAACAAAATTGGAGGCTCACTCCTTGGGCTCCCTGGATG
	ACCCCCAACATCCTTCCTCACTTCCATTCCTTCCCAGCATCCAGATCAGCCACTTGTC
	CATCGCCAGCAGCCAGGTGGAGCTGGTGGAAGCCAAGTCCATTGATGTCTCCATTCAG
	AACGTGTCTGTGGTCTTCAAGGGGACCCTGAAGTATGGCTACACCACTGCCTGGTGGT
	AAGCATTCCTGTCAGCTGATGCCCCATGCCCTGGCCCTCTCTGGGCTGGAGGGCTGAA
	TGAGGGTCCTGGGTCCTTGGCTCTTTCCAGGCTGGGTATTGATCAGTCCATTGACTTC
	GAGATCGACTCTGCCATTGACCTCCAGATCAACACACAGCTGAGTATGTGTCAAGCGT
	CCTCTGGGGAAGTGGGAGCTGGACTCCAGGGCTTGGCCTCAGCAGAGGGGGAGGTTGT
	GCAGGCAGAGGGTTCTGGGGCCACCAAAGGAGGCCCAGCCTGGGAAGTTTGCAGGGGT
	GGGGACCCCAGAGCTGGCCAAGCTCTTGACTGGCCTGGGCAGCATGTGGATACCATCT
	GATAGCGGAGGCTGCCCTGAGGTCATGTCGGGTCTCCCTGCAGCCTGTGACTCTGGTA
	GAGTGCGGACCGATGCCCCTGACTGCTACCTGTCTTTCCATAAGCTGCTCCTGCATCT
	CCAAGGGGAGCGAGAGTAAGTACACCACCCTGTGGCCCCCATTCCTGCTCGTGCCCAT
	CCTGTTAGTGTGTCCACGGCTCCTTCCAGGCTCAACCCCACACAGGGCATGCTTGTGG
	GTGGCCAAACCTGAGGGCAGCAATACCTTCAGTGGGGTCACTTCCTACCCCCTCCCAT
	CAATACACCCTCAAAGGCTGGAAACAACAATAACCAACAGCTAGTAACTAACAGCTAT
	TAAGAACTTGCTGTGTG
	ORF Start: ATG at 85	ORF Stop: TAA at 2842
	SEQ ID NO: 130	919	MW at 101671.2Da
		aa
NOV32a,	MECALLLACAFPAAGSGPPRGLAGLGRVAKALQLCCLCCASVAAALASDSSSGASGLN
CG56735-
01 Protein	DDYVFVTPVEVDSAGSYISHDILHNGRKKRSAQNARSSLHYRFSAFGQELHLELKPSA
Sequence
	ILSSHFIVQVLGKDGASETQKPEVQQCFYQEFIRNDSSSSVAVSTCAGLSGLIRTRKN
	EFLISPLPQLLAQEHNYSSPAGHHPHVLYKRTAEEKIQRYRGYPGSGRNYPGYSPSHI
	PHASQSRETEYHHRRLQKQHFCGRRKKYAPKPPTEDTYLRFDEYGSSGRPRRSAGKSQ
	KGLNVETLVVADKKMVEKHGKGNVTTYILTVMNMVSGLFKDGTIGSDINVVVVSLILL
	EQEPGGLLINHHADQSLNSFCQWQSALIGKNGKRHDHAILLTGFDICSWKNEPCDTLG
	FAPISGMCSKYRSCTINEDTGLGLAFTIAHESGHNFGMIHDGEGNPCRKAEGNIMSPT
	LTGNNGVFSWSSCSRQYLKKFLSTPQAGCLVDEPKQAGQYKYPDKLPGQIYDADTQCK
	WQFGAKAKLCSLGFVKDICKSLWCHRVGHRCETKFMPAAEGTVCGLSMVNCILWCRQG
	QCVKFGELGPRPIHGQWSAWSKWSECSRTCGGGVKFQERHCNNPKPQYGGLFCPGSSR
	IYQLCNINPCNENSLDFRAQQCAEYNSKPFRGWFYQWKPYTKVEEEDRCKLYCKAENF
	EFFFAMSGKVKDGTPCSPNKNDVCIDGVCELVGCDHELGSKAVSDACGVCKGDNSTCK
	FYKGLYLNQHKANEYYPVVLIPAGARSIEIQELQVSSSYLAVRSLSQKYYLTGGWSID
	WPGEFPFAGTTFEYQRSFNRPERLYAPGPTNETLVFETKLEAHSLGSLDDPQHPSSLP
	FLPSIQISHLSIASSQVELVEAKSIDVSIQNVSVVFKGTLKYGYTTAWW
	SEQ ID NO: 131	2940 bp
NOV32b,	TGCGGCCGCGGAAAGAATGCGCGCCGCCCGTGCGCTCCGCCTGCCGCGTCTGGCCACC
CG56735-
02 DNA	CGCAGCCGCCGCGTCCGCACCTGACCATGGAGTGCGCCCTCCTGCTCGCGTGTGCCTT
Sequence
	CCCGGCTGCGGGTTCGGGCCCGCCGAGGGGCCTGGCGGGACTGGGGCGCGTGGCCAAG
	GCGCTCCAGCTGTGCTGCCTCTGCTGTGCGTCGGTCGCCGCGGCCTTAGCCAGTGACA
	GCAGCAGCGGCGCCAGCGGATTAAATGATGATTACGTCTTTGTCACGCCAGTAGAAGT
	AGACTCAGCCGGGTCATATATTTCACACGACATTTTGCACAACGGCAGGAAAAAGCGA
	TCGGCGCAGAATGCCAGAAGCTCCCTGCACTACCGATTTTCAGCATTTGGACAGGAAC
	TGCACTTAGAACTTAAGCCCTCGGCGATTTTGAGCAGTCACTTTATTGTCCAGGTACT
	TGGAAAAGATGGTGCTTCAGAGACTCAGAAACCCGAGGTGCAGCAATGCTTCTATCAG
	GAATTTATCAGAAATGACAGCTCCTCCTCTGTCGCTGTGTCTACGTGTGCTGGCTTGT
	CAGGTTTAATAAGGACACGAAAAAATGAATTCCTCATCTCGCCATTACCTCAGCTTCT
	GGCCCAGGAACACAACTACAGCTCCCCTGCGGGTCACCATCCTCACGTACTGTACAAA
	AGGACAGCAGAGGAGAAGATCCAGCGGTACCGTGGCTACCCCGGCTCTGGCCGGAATT
	ATCCTGGTTACTCCCCAAGTCACATTCCCCATGCATCTCAGAGTCGAGAGACAGAGTA
	TCACCATCGAAGGTTGCAAAAGCAGCATTTTTGTGGACGACGCAAGAAATATGCTCCC
	AAGCCTCCCACAGAGGACACCTATCTAAGGTTTGATGAATATGGGAGCTCTGGGCGAC
	CCAGAAGATCAGCTGGAAAATCACAAAAGGGCCTCAATGTGGAAACCCTCGTGGTGGC
	AGACAAGAAAATGGTGGAAAAGCATGGCAAGGGAAATGTCACCACATACATTCTCACA
	GTAATGAACATGGTTTCTGGCCTATTTAAAGATGGGACTATTGGAAGTGACATAAACG
	TGGTTGTGGTGAGCCTAATTCTTCTGGAACAAGAACCTGGAGGATTATTGATCAACCA
	TCATGCAGACCAGTCTCTGAATAGTTTTTGTCAATGGCAGTCTGCCCTCATTGGAAAG
	AATGGCAAGAGACATGATCATACCATCTTACTAACAGGATTTGATATTTGTTCTTGGA
	AGAATGAACCATGTGACACTCTAGGGTTTGCCCCCATCAGTGGAATGTGCTCTAAGTA
	CCGAAGTTGTACCATCAATGAGGACACAGGACTTGGCCTTGCCTTCACCATCGCTCAT
	GAGTCAGGGCACAACTTTGGTATGATTCACGACGGAGAAGGGAATCCCTGCAGAAAGG
	CTGAAGGCAATATCATGTCTCCCACACTGACCGGAAACAATGGAGTGTTTTCATGGTC
	TTCCTGCAGCCGCCAGTATCTCAAGAAATTCCTCAGCACACCTCAGGCGGGGTGTCTA
	GTGGATGAGCCCAAGCAAGCAGGACAGTATAAATATCCGGACAAACTACCAGGACAGA
	TTTATGATGCTGACACACAGTGTAAATGGCAATTTGGAGCAAAAGCCAAGTTATGCAG
	CCTTGGTTTTGTGAAGGATATTTGCAAATCACTTTGGTGCCACCGAGTAGGCCACAGG
	TGTGAGACCAAGTTTATGCCCGCAGCAGAAGGGACCGTTTGTGGCTTGAGTATGTGGT
	GTCGGCAAGGCCAGTGCGTAAAGTTTGGGGAGCTCGGGCCCCGGCCCATCCACGGCCA
	GTGGTCCGCCTGGTCGAAGTGGTCAGAATGTTCCCGGACATGTGGTGGAGGAGTCAAG
	TTCCAGGAGAGACACTGCAATAACCCCAAGCCTCAGTATGGTGGCATATTCTGTCCAG
	GTTCTAGCCGTATTTATCAGCTGTGCAATATTAACCCTTGCAATGAAAATAGCTTGGA
	TTTTCGGGCTCAACAGTGTGCAGAATATAACAGCAAACCTTTCCGTGGATGGTTCTAC
	CAGTGGAAACCCTATACAAAAGTGGAAGAGGAAGATCGATGCAAACTGTACTGCAAGG
	CTGAGAACTTTGAATTTTTTTTTGCAATGTCCGGCAAAGTGAAAGATGGAACTCCCTG
	CTCCCCAAACAAAAATGATGTTTGTATTGACGGGGTTTGTGAACTAGTGGGATGTGAT
	CATGAACTAGGCTCTAAAGCAGTTTCAGATGCTTGTGGCGTTTGCAAAGGTGATAATT
	CAACTTGCAAGTTTTATAAAGGCCTGTACCTCAACCAGCATAAAGCAAATGAATATTA
	TCCGGTGGTCCTCATTCCAGCTGGCGCCCGAAGCATCGAAATCCAGGAGCTGCAGGTT
	TCCTCCAGTTACCTCGCAGTTCGAAGCCTCAGTCAAAAGTATTACCTCACCGGGGGCT
	GGAGCATCGACTGGCCTGGGGAGTTCCCCTTCGCTGGGACCACGTTTGAATACCAGCG
	CTCTTTCAACCGCCCGGAACGTCTGTACGCGCCAGGGCCCACAAATGAGACGCTGGTC
	TTTGAAACAAAATTGGAGGCTCACTCCTTGGGCTCCCTGGATGACCCCCAACATCCTT
	CCTCACTTCCATTCCTTCCCAGCATCCAGATCAGCCACTTGTCCATCGCCAGCAGCCA
	GGTGGAGCTGGTGGAAGCCAAGTCCATTGATGTCTCCATTCAGAACGTGTCTGTGGTC
	TTCAAGGGGACCCTGAAGTATGGCTACACCACTGCCTGGTGGTAAGCATTCCTGTCAG
	CTGATGCCCCATGCCCTGGCCCTCTCTGGGCTGGAGGGCTGAATGAGGGTCCTGGGTC
	CTTGGCTCTTTCCAGGCTGGGTATTGATCAGTCCATTGAC
	ORF Start: ATG at 85	ORF Stop: TAA at 2827
	SEQ ID NO: 132	914	MW at 101158.6Da
		aa
NOV32b,	MECALLLACAFPAAGSGPPRGLAGLGRVAKALQLCCLCCASVAAALASDSSSGASGLN
CG56735-
02 Protein	DDYVFVTPVEVDSAGSYISHDILHNGRKKRSAQNARSSLHYRFSAFGQELHLELKPSA
Sequence
	ILSSHFIVQVLGKDGASETQKPEVQQCFYQEFIRNDSSSSVAVSTCAGLSGLIRTRKN
	EFLISPLPQLLAQEHNYSSPAGHHPHVLYKRTAEEKIQRYRGYPGSGRNYPGYSPSHI
	PHASQSRETEYHHRRLQKQHFCGRRKKYAPKPPTEDTYLRFDEYGSSGRPRRSAGKSQ
	KGLNVETLVVADKKMVEKHGKGNVTTYILTVMNMVSGLFKDGTIGSDINVVVVSLILL
	EQEPGGLLINHHADQSLNSFCQWQSALIGKNGKRHDHTILLTGFDICSWKNEPCDTLG
	FAPISGMCSKYRSCTINEDTGLGLAFTIAHESGHNFGMIHDGEGNPCRKAEGNIMSPT
	LTGNNGVFSWSSCSRQYLKKFLSTPQAGCLVDEPKQAGQYKYPDKLPGQIYDADTQCK
	WQFGAKAKLCSLGFVKDICKSLWCHRVGHRCETKFMPAAEGTVCGLSMWCRQGQCVKF
	GELGPRPIHGQWSAWSKWSECSRTCGGGVKFQERHCNNPKPQYGGIFCPGSSRIYQLC
	NINPCNENSLDFRAQQCAEYNSKPFRGWFYQWKPYTKVEEEDRCKLYCKAENFEFFFA
	MSGKVKDGTPCSPNKNDVCIDGVCELVGCDHELGSKAVSDACGVCKGDNSTCKFYKGL
	YLNQHKANEYYPVVLIPAGARSIEIQELQVSSSYLAVRSLSQKYYLTGGWSIDWPGEF
	PFAGTTFEYQRSFNRPERLYAPGPTNETLVFETKLEAHSLGSLDDPQHPSSLPFLPSI
	QISHLSIASSQVELVEAKSIDVSIQNVSVVFKGTLKYGYTTAWW
	SEQ ID NO: 155	624 bp
NOV32c,	GGATCCGTGGAAACCCTCGTGGTGGCAGACAAGAAAATGGTGGAAAAGCATGGCAAGG
174124733
DNA	GAAATGTCACCACATACATTCTCACAGTAATGAACATGGTTTCTGGCCTATTTAAAGA
Sequence
	TGGGACTATTGGAAGTGACATAAACGTGGTTGTGGTGAGCCTAATTCTTCTGGAACAA
	GAACCTGGAGGATTATTGATCAACCATCATGCAGACCAGTCTCTGAATAGTTTTTGTC
	AATGGCAGTCTGCCCTCATTGGAAAGAATGGCAAGAGACATGATCATGCCATCTTACT
	AACAGGATTTGATATTTGTTCTTGGAAGAATGAACCATGTGACACTCTAGGGTTTGCC
	CCCATCAGTGGAATGTGCTCTAAGTACCGAAGTTGTACCATCAATGAGGACACAGGAC
	TTGGCCTTGCCTTCACCATCGCTCATGAGTCAGGGCACAACTTTGGTATGATTCACGA
	CGGAGAAGGGAATCCCTGCAGAAAGGCTGAAGGCAATATCATGTCTCCCACACTGACC
	GGAAACAATGGAGTGTTTTCATGGTCTTCCTGCAGCCGCCAGTATCTCAAGAAATTCC
	TCAGCACACCTCAGGCGGGGTGTCTAGTGGATGAGCCCCTCGAG
	SEQ ID NO: 156	207	MW:
		aa
NOV32c,	GSVETLWADKKMVEKHGKGNVTTYILTVMNMVSGLFKDGTIGSDINVVVVSLILLEQE
174124733
Protein	PGGLLINHHADQSLNSFCQWQSALIGKNGKRHDHAILLTGFDICSWKNEPCDTLGFAP
Sequence
	ISGMCSKYRSCTINEDTGLGLAFTIAHESGHNFGMIHDGEGNPCRKAEGNIMSPTLTG
	NNGVFSWSSCSRQYLKKFLSTPQAGCLVDEPLE

[0486] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 32B.

TABLE 32B
Comparison of NOV32a against NOV32b.
Protein	NOV32a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV32b	1 . . . 919	877/919 (95%)
	1 . . . 914	878/919 (95%)

[0487] Further analysis of the NOV32a protein yielded the following properties shown in Table 32C.

TABLE 32C
Protein Sequence Properties NOV32a
PSort     0.6400 probability located in plasma membrane;
analysis: 0.4600 probability located in Golgi body; 0.3700 probability
          located in endoplasmic reticulum (membrane); 0.1000
          probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 48 and 49
analysis:

[0488] A search of the NOV32a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 32D.

TABLE 32D
Geneseq Results for NOV32a
		NOV32a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU72893	Human metalloprotease partial	305 . . . 858	541/554 (97%)	0.0
	protein sequence #5 - Homo sapiens,	1 . . . 549	544/554 (97%)
	934 aa. [WO200183782-A2, 08 NOV. 2001]
AAU72891	Human metalloprotease partial	20 . . . 858	494/868 (56%)	0.0
	protein sequence #3 - Homo sapiens,	9 . . . 850	608/868 (69%)
	1224 aa. [WO200183782-A2, 08 NOV. 2001]
AAE03572	Human protease−related protein #1 -	59 . . . 858	332/822 (40%)	e−179
	Homo sapiens, 908 aa.	40 . . . 821	476/822 (57%)
	[WO200142468-A1, 14 JUN. 2001]
AAB86947	Human metalloprotease MPTS-15	59 . . . 858	332/822 (40%)	e−179
	protein - Homo sapiens, 959 aa.	40 . . . 821	476/822 (57%)
	[DE10107360-A1, 06 SEP. 2001]
AAE03583	Human protease−related protein #12 -	167 . . . 858	296/705 (41%)	e−163
	Homo sapiens, 757 aa.	5 . . . 670	413/705 (57%)
	[WO200142468-A1, 14 JUN. 2001]

[0489] In a BLAST search of public sequence datbases, the NOV32a protein was found to have homology to the proteins shown in the BLASTP data in Table 32E.

TABLE 32E
Public BLASTP Results for NOV32a
		NOV32a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q8TE60	ADAMTS 18 protein - Homo sapiens	1 . . . 858	840/858 (97%)	0.0
	(Human), 1081 aa.	1 . . . 852	844/858 (97%)
Q8TE57	Metalloprotease disintegrin 16 with	20 . . . 858	494/868 (56%)	0.0
	thrombospondin type I motif - Homo	9 . . . 850	608/868 (69%)
	sapiens (Human), 1072 aa.
CAD20434	Sequence 8 from Patent WO0188156 -	59 . . . 894	322/861 (37%)	e−153
	Homo sapiens (Human), 1044 aa	37 . . . 854	454/861 (52%)
	(fragment).
CAD20435	Sequence 11 from Patent WO0188156 -	59 . . . 847	309/806 (38%)	e−152
	Homo sapiens (Human), 814 aa.	37 . . . 799	434/806 (53%)
P58397	ADAMTS-12 precursor (EC 3.4.24.-)	60 . . . 846	305/804 (37%)	e−151
	(A disintegrin and metalloproteinase	51 . . . 793	443/804 (54%)
	with thrombospondin motifs 12)
	(ADAM-TS 12) (ADAM- TS12) -
	Homo sapiens (Human), 1593 aa.

[0490] PFam analysis predicts that the NOV32a protein contains the domains shown in the Table 32F.

TABLE 32F
Domain Analysis of NOV32a
		Identities/
	NOV32a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
Pep_M12B_propep	111 . . . 222	26/119 (22%)	6e−10
		71/119 (60%)
Reprolysin	295 . . . 498	66/221 (30%)	1.1e−21
		158/221 (71%)
tsp_1	598 . . . 648	23/54 (43%)	1.2e−12
		36/54 (67%)
LBP_BPI_CETP	874 . . . 918	14/53 (26%)	7.9e−08
		45/53 (85%)

Example 33

[0491] The NOV33 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 33A.

TABLE 33A
NOV33 Sequence Analysis
	SEQ ID NO: 133	1282 bp
NOV33a,	CAAGGGATGGCGATGGCGTACTTGGCTTGGAGACTGGCGCGGCGTTCGTGTCCGAGTT
CG57635-02 DNA
Sequence	CTCTGCAGGTCACTAGTTTCCCGGTAGTTCAGCTGCACATGAATAGAACAGCAATGAG
	AGCCAGTCAGAAGGACTTTGAAAATTCAATGAATCAAGTGAAACTCTTGAAAAAGGAT
	CCAGGAAACGAAGTGAAGCTAAAACTCTACGCGCTATATAAGCAGGCCACTGAAGGAC
	CTTGTAGCATGCCCAAACCAGGTGTATTTGACTTGATCAACAAGGCCAAATGGGACGC
	ATGGAATGCCCTTGGCAGCCTGCCCAAGGAAGCTGCCAGGCAGAACTATGTGGATTTG
	GTGTCCAGTTTGAGTCCTTCATTGGAATCCTCTAGTCAGGTGGAGCCTGGAACAGACA
	GGAAATCAACTGGGTTTGAAACTCTGGTGGTGACCTCCGAAGATGGCATCACAAAGAT
	CATGTTCAACCGGCCCAAAAAGAAAAATGCCATAAACACTGAGATGTATCATGAAATT
	ATGCGTGCACTTAAAGCTGCCAGCAAGGATGACTCAATCATCACTGTTTTAACAGGAA
	ATGGTGACTATTACAGTAGTGGGAATGATCTGACTAACTTCACTGATATTCCCCCTGG
	TGGAGTAGAGGAGAAAGCTAAAAATAATGCCGTTTTACTGAGGGAATTTGTGGGCTGT
	TTTATAGATTTTCCTAAGCCTCTGATTGCAGTGGTCAATGGTCCAGCTGTGGGCATCT
	CCGTCACCCTCCTTGGGCTATTCGATGCCGTGTATGCATCTGACAGGGCAACATTTCA
	TACACCATTTAGTCACCTAGGCCAAAGTCCGGAAGGATGCTCCTCTTACACTTTTCCG
	AAGATAATGAGCCCAGCCAAGGCAACAGAGATGCTTATTTTTGGAAAGAAGTTAACAG
	CGGGAGAGGCATGTGCTCAAGGACTTGTTACTGAAGTTTTCCCTGATAGCACTTTTCA
	GAAAGAAGTCTGGACCAGGCTGAAGGCATTTGCAAAGCTTCCCCCAAATGCCTTGAGA
	ATTTCAAAAGAGGTAATCAGGAAAAGAGAGAGAGAAAAACTACACGCTGTTAATGCTG
	AAGAATGCAATGTCCTTCAGGGAAGATGGCTATCAGATGAATGCACAAATGCTGTGGT
	GAACTTCTTATCCAGAAAATCAAAACTGTGATGACCACTACAGCAGAGTAAAGCATGT
	CCAAGGAAGGATGTGCTGTTACCTCTGATTTCCAGTACTGGAACTAAATAAGCTTCAT
	TGTGCC
	ORF Start: ATG at 7	ORF Stop: TGA at 1189
	SEQ ID NO: 134	394 aa	MW at 43557.6Da
NOV33a,	MAMAYLAWRLARRSCPSSLQVTSFPVVQLHMNRTAMRASQKDFENSMNQVKLLKKDPG
CG57635-02
Protein Sequence	NEVKLKLYALYKQATEGPCSMPKPGVFDLINKAKWDAWNALGSLPKEAARQNYVDLVS
	SLSPSLESSSQVEPGTDRKSTGFETLVVTSEDGITKIMFNRPKKKNAINTEMYHEIMR
	ALKAASKDDSIITVLTGNGDYYSSGNDLTNFTDIPPGGVEEKAKNNAVLLREFVGCFI
	DFPKPLIAVVNGPAVGISVTLLGLFDAVYASDRATFHTPFSHLGQSPEGCSSYTFPKI
	MSPAKATEMLIFGKKLTAGEACAQGLVTEVFPDSTFQKEVWTRLKAFAKLPPNALRIS
	KEVIRKREREKLHAVNAEECNVLQGRWLSDECTNAVVNFLSRKSKL
	SEQ ID NO: 135	1011 bp
NOV33b,	GCGATGGCGTACTTGGCTTGGAGACTGGCGCGGCGTTCGTGTCCGAGGTCACTAGTTT
CG57635-03 DNA
Sequence	CCCGGTAGTTCAGCTGCACATGAATAGAACAGCAATGAGAGCCAGTCAGAAGGACTTT
	GAAAATTCAATGAATCAAGTGAAACTCTTGAAAAAGGATCCAGGAAACGAAGTGAAGC
	TAAAACTCTACGCGCTATATAAGCAGGCCACTGAAGGACCTTGTAACATGCCCAAACC
	AGGTGTATTTGACTTGATCAACAAGGCCAAATGGGACGCATGGAATGCCCTTGGCAGC
	CTGTCCAAGGAAGCTGCCAGGCAGAACTATGTGGATTTGGTGTCCAGTTTGAGTCCTT
	CATTGGAATCCTCTAGTCAGGTGGAGCCTGGAACAGACAGGAAATCAACTGGGTTTGA
	AACTCTGGTGGTGACCTCCGAAGATGGCATCACAAAGATCATGTTCAACCGGCCCAAA
	AAGAAAAATGCCGTTTTACTGAGGGAATTTGTGGGCTGTTTTATAGATTTTCCTAAGC
	CTCTGATTGCAGTGGTCAATGGTCCAGCTGTGGGCATCTCCGTCACCCTCCTTGGGCT
	ATTCGATGCCGTGTATGCATCTGACAGGGCAACATTTCATACACCATTTAGCCACCTA
	GGCCAAAGTCCGGAAGGATGCTCCTCTTACACTTTTCCGAAGATAATGAGCCCAGCCA
	AGGCAACAGAGATGCTTATTTTTGGAAAGAAGTTAACAGCGGGAGAGGCATGTGCTCA
	AGGACTTGTTACTGAAGTTTTCCCTGATAGCACTTTTCAGAAAGAAGTCTGGACCAGG
	CTGAAGGCATTTGCAAAGCTTCCCCCAAATGCCTTGAGAATTTCAAAAGAGGTGATCA
	GGAAAAGAGAGAGAGAAAAACTACACGCTGTTAATGCTGAAGAATGCAATGTCCTTCA
	GGGAAGATGGCTATCAGATGAATGCACAAATGCTGTGGTGAACTTCTTATCCAGAAAA
	TCAAAACTGTGATGACCACTACAGC
	ORF Start: ATG at 93	ORF Stop: TGA at 996
	SEQ ID NO: 136	301 aa	MW at 33325.1Da
NOV33b,	MRASQKDFENSMNQVKLLKKDPGNEVKLKLYALYKQATEGPCNMPKPGVFDLINKAKW
CG57635-03
Protein Sequence	DAWNALGSLSKEAARQNYVDLVSSLSPSLESSSQVEPGTDRKSTGFETLVVTSEDGIT
	KIMFNRPKKKNAVLLREFVGCFIDFPKPLIAVVNGPAVGISVTLLGLFDAVYASDRAT
	FHTPFSHLGQSPEGCSSYTFPKIMSPAKATEMLIFGKKLTAGEACAQGLVTEVFPDST
	FQKEVWTRLKAFAKLPPNALRISKEVIRKREREKLHAVNAEECNVLQGRWLSDECTNA
	VVNFLSRKSKL

[0492] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 33B.

TABLE 33B
Comparison of NOV33a against NOV33b.
	NOV33a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV33b	218 . . . 394	176/177 (99%)
	125 . . . 301	176/177 (99%)

[0493] Further analysis of the NOV33a protein yielded the following properties shown in Table 33C.

TABLE 33C
Protein Sequence Properties NOV33a
PSort     0.8000 probability located in microbody (peroxisome); 0.7446
analysis: probability located in mitochondrial inner membrane; 0.5142
          probability located in mitochondrial matrix space; 0.5142
          probability located in mitochondrial intermembrane space
SignalP   Cleavage site between residues 14 and 15
analysis:

[0494] A search of the NOV33a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 33D.

TABLE 33D
Geneseq Results for NOV33a
		NOV33a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM93539	Human polypeptide, SEQ ID NO:	31 . . . 394	363/364 (99%)	0.0
	3287 - Homo sapiens, 364 aa.	1 . . . 364	364/364 (99%)
	[EP1130094-A2, 05 SEP. 2001]
AAB81822	Human endozepine−like ENDO9 SEQ	36 . . . 394	358/359 (99%)	0.0
	ID NO: 32 - Homo sapiens, 359 aa.	1 . . . 359	359/359 (99%)
	[WO200125436-A2, 12 APR. 2001]
AAY07048	Renal cancer associated antigen	82 . . . 384	244/304 (80%)	e−125
	precursor sequence - Homo sapiens,	4 . . . 297	255/304 (83%)
	298 aa. [WO9904265-A2, 28 JAN. 1999]
AAB63531	Human gastric cancer associated	1 . . . 217	216/217 (99%)	e−122
	antigen protein sequence SEQ ID	1 . . . 217	217/217 (99%)
	NO: 893 - Homo sapiens, 217 aa.
	[WO200073801-A2, 07 DEC. 2000]
AAB63535	Human gastric cancer associated	1 . . . 217	214/217 (98%)	e−120
	antigen protein sequence SEQ ID	1 . . . 217	215/217 (98%)
	NO: 897 - Homo sapiens, 217 aa.
	[WO200073801-A2, 07 DEC. 2000]

[0495] In a BLAST search of public sequence datbases, the NOV33a protein was found to have homology to the proteins shown in the BLASTP data in Table 33E.

TABLE 33E
Public BLASTP Results for NOV33a
		NOV33a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9BUE9	Peroxisomal D3,D2-enoyl-CoA	1 . . . 394	393/394 (99%)	0.0
	isomerase - Homo sapiens (Human), 394 aa.	1 . . . 394	394/394 (99%)
Q9H0T9	Hypothetical 43.6 kDa protein - Homo	1 . . . 394	392/394 (99%)	0.0
	sapiens (Human), 394 aa.	1 . . . 394	393/394 (99%)
O75521	Peroxisomal 3,2-trans-enoyl-CoA	36 . . . 394	357/359 (99%)	0.0
	isomerase (EC 5.3.3.8) (Dodecenoyl-	1 . . . 359	358/359 (99%)
	CoA delta-isomerase) (D3,D2-enoyl-
	CoA isomerase) (DBI-related protein 1)
	(DRS-1) (Hepatocellular carcinoma-
	associated antigen 88) - Homo sapiens
	(Human), 359 aa.
Q99M61	Similar to peroxisomal delta3, delta2-	36 . . . 394	271/359 (75%)	e−157
	enoyl-coenzyme A isomerase - Mus	1 . . . 358	310/359 (85%)
	musculus (Mouse), 358 aa.
Q9D785	Peroxisomal delta3, delta2-enoyl-	36 . . . 394	270/359 (75%)	e−157
	coenzyme A isomerase - Mus musculus	1 . . . 358	310/359 (86%)
	(Mouse), 358 aa.

[0496] PFam analysis predicts that the NOV33a protein contains the domains shown in the Table 33F.

TABLE 33F
Domain Analysis of NOV33a
		Identities/
	NOV33a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
ACBP	39 . . . 123	43/89 (48%)	1.7e−38
		70/89 (79%)
ECH	151 . . . 322	55/177 (31%)	1e−15
		114/177 (64%)

Example 34

[0497] The NOV34 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 34A.

TABLE 34A
NOV34 Sequence Analysis
	SEQ ID NO: 137	1355 bp
NOV34a,	GAATTCCGGCCAAGATGGCAGCAATGAGGAAGGCGCTTCCGCGGCGACTGGTGGGCTT
CG96859-02 DNA
Sequence	GGCGTCCCTCCGGGCTGTCAGCACCTCATCTATGGGCACTTTACCAAAGCGGGTGAAA
	ATTGTGGAAGTTGGTCCCCGAGATGGACTACAAAATGAAAAGAATATCGTATCTACTC
	CAGTGAAAATCAAGCTGATAGACATGCTTTCTGAAGCAGGACTCTCTGTTATAGAAAC
	CACCAGCTTTGTGTCTCCTAAGTGGGTTCCCCAGATGGGTGACCACACTGAAGTCTTG
	AAGGGCATTCAGAAGTTTCCTGGCATCAACTACCCAGTCCTGACCCCAAATTTGAAAG
	GCTTCGAGGCAGCGGTCACCAAGAAGTTCTACTCAATGGGCTGCTACGAGATCTCCCT
	GGGGGACACCATTGGTGTGGGCACCCCAGGGATCATGAAAGACATGCTGTCTGCTGTC
	ATGCAGGAAGTGCCTCTGGCTGCCCTGGCTGTCCACTGCCATGACACCTATGGTCAAG
	CCCTGGCCAACACCTTGATGGCCCTGCAGATGGGAGTGAGTGTCGTGGACTCTTCTGT
	GGCAGGACTTGGAGGCTGTCCCTACGCACAGGGGGCATCAGGAAACTTGGCCACAGAA
	GACCTGGTCTACATGCTAGAGGGCTTGGGCATTCACACGGGTGTGAATCTCCAGAAGC
	TTCTGGAAGCTGGAAACTTTATCTGTCAAGCCCTGAACAGAAAAACTAGCTCCAAAGT
	GGCTCAGGCTACCTGTAAACTCTGAGCCCCTTGCCCACCTGAAGCCCTGGGGATGATG
	TGGAAATAGGGGCACACACAGATGATTCATGGATGGGGACATGGAAATGAGAATAGGT
	TAAATGGTGCAGGTACCTCATAGCCAGCTCTACACAGAGGTCTCTCCTGGCAGAAAGC
	AGGCGAAGGGCAGGAGGAGCTGCTTGGCAGAAGGACCTCCTGCCCAGACCTGAGGAGT
	GAGAGGCTTTGAGGGCTGAAGTCTCCCTTTGTTACGGACCCTGGCCCAGGAGTTGAAT
	GCCTGAGGACGTGTGGGAACCCCGTTCCCTACTTAGCATGATCCTTGAGTCTCCTCTC
	TGGATGGAATCCGCGAGCTGGCCACCTGGCCACCCTCTACACGGCTCCACCCTGCCAT
	GGCCGTGGGGCCCTTGCTCTCTGACTTCTCAGGACACAGGTCATGGAGGTTCTTCCCA
	AGCTGGCAGAGGCCATTTGTGGAAAGTGGAGAGCTACGTGGTGGCCGTCTGCCAACTC
	CAGCATCTCTGGAAAATCTCCACGCTGAATGTGATTTTTGAAAACAGCTTATGTAATT
	AAAGGTTGAATGGCACATCAT
	ORF Start: ATG at 15	ORF Stop: TGA at 777
	SEQ ID NO: 138	254 aa	MW at 26909.3Da
NOV34a,	MAAMRKALPRRLVGLASLRAVSTSSMGTLPKRVKIVEVGPRDGLQNEKNIVSTPVKIK
CG96859-02
Protein Sequence	LIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTPNLKGFEAA
	VTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANT
	LMALQMGVSVVDSSVAGLGGCPYAQGASGNLATEDLVYMLEGLGIHTGVNLQKLLEAG
	NFICQALNRKTSSKVAQATCKL
	SEQ ID NO: 139	1041 bp
NOV34b,	AAATTCCGGCCAAGATGGCAGCAATGAGGAAGGCGCTTCCGCGGCGACTGGTGGGCTT
CG96859-03 DNA
Sequence	GGCGTCCCTCCGGGCTGTCAGCACCTCATCTATGGGCACTTTACCAAAGCGGGTGAAA
	ATTGTGGAAGTTGGTCCCCGAGATGGACTACAAAATGAAAAGAATATCGTATCTACTC
	CAGTGAAAATCAAGCTGATAGACATGCTTTCTGAAGCAGGACTCTCTGTTATAGAAAC
	CACCAGCTTTGTGTCTCCTAAGTGGGTTCCCCAGATGGGTGACCACACTGAAGTCTTG
	AAGGGCATTCAGAAGTTTCCTGGCATCAACTACCCAGTCCTGACCCCAAATTTGAAAG
	GCTTCGAGGCAGCGGTTGCTGCTGGAGCCAAGGAAGTAGTCATCTTTGGAGCTGCCTC
	AGAGCTCTTCACCAAGAAGAACATCAATTGTTCCATAGAGGAGAGTTTTCAGAGGTTT
	GACGCAATCCTGAAGGCAGCGCAGTCAGCCAATATTTCTGTGCGGGGGTACGTCTCCT
	GTGCTCTTGGCTGCCCTTATGAAGGGAAGATCTCCCCAGCTAAAGTAGCTCAGGTCAC
	CAAGAAGTTCTACTCAATGGGCTGCTACGAGATCTCCCTGGGGGACACCATTGGTGTG
	GGCACCCCAGGGATCATGAAAGACATGCTGTCTGCTGTCATGCAGGAAGTGCCTCTGG
	CTGCCCTGGCTGTCCACTGCCATGACACCTATGGTCAAGCCCTGGCCAACACCTTGAT
	GGCCCTGCAGATGGGAGTGAGTGTCGTGGACTCTTCTGTGGCAGGACTTGGAGGCTGT
	CCCTACGCACAGGGGGCATCAGGAAACTTGGCCACAGAAGACCTGGTCTACATGCTAG
	AGGGCTTGGGCATTCACACGGGTGTGAATCTCCAGAAGCTTCTGGAAGCTGGAAACTT
	TATCTGTCAAGCCCTGAACAGAAAAACTAGCTCCAAAGTGGCTCAGGCTACCTGTAAA
	CTCTGAGCCCCTTGCCCACCTGAAGGCCTGGGGATGATGTGGAAATAAGGGGCAT
	ORF Start: ATG at 15	ORF Stop: TGA at 990
	SEQ ID NO: 140	325 aa	MW at 34359.8Da
NOV34b,	MAAMRKALPRRLVGLASLRAVSTSSMGTLPKRVKIVEVGPRDGLQNEKNIVSTPVKIK
CG96859-03
Protein Sequence	LIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTPNLKGFEAA
	VAAGAKEVVIFGAASELFTKKNINCSIEESFQRFDAILKAAQSANISVRGYVSCALGC
	PYEGKISPAKVAEVTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAV
	HCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPYAQGASGNLATEDLVYMLEGLGI
	HTGVNLQKLLEAGNFICQALNRKTSSKVAQATCKL
	SEQ ID NO: 141	788 bp
NOV34c,	GATGGCAGCAATGAGGAAGGCGCTTCCGCGGCGACTGGTGGGCTTGGCGTCCCTCCGG
CG96859-04 DNA
Sequence	GCTGTCAGCACCTCATCTATGGGCACTTTACCAAAGCGGGTGAAAATTGTGGAAGTTG
	GTCCCCGAGATGGACTACAAAATGAAAGGAATATCGTATCTACTCCAGTGAAAATCAA
	GCTGATAGACATGCTTTCTGAAGCAGGACTCTCTGTTATAGAAACCACCAGCTTTGTG
	TCTCCTAAGTGGGTTCCCCAGATGGGTGACCACACTGAAGTCTTGAAGGGCATTCAGA
	AGTTTCCTGGCATCAACTACCCAGTCCTGACCCCAAATTTGAAAGGCTTCGAGGCAGC
	GGTCACCAAGAAGTTCTACTCAATGGGCTGCTACGAGATCTCCCTGGGGGACACCATT
	GGTGTGGGCACCCCAGGGATCATGAAAGACATGCTGTCTGCTGTCATGCAGGAAGTGC
	CTCTGGCTGCCCTGGCTGTCCACTGCCATGACACCTATGGTCAAGCCCTGGCCAACAC
	CTTGATGGCCCTGCAGATGGGAGTGAGTGTCGTGGACTCTTCTGTGGCAGGACTTGGA
	GGCTGTCCCTACGCACAGGGGGCATCAGGAAACTTGGCCACAGAAGACCTGGTCTACA
	TGCTAGAGGGCTTGGGCATTCACACGGGTGTGAATCTCCAGAAGCTTCTGGAAGCTGG
	AAACTTTATCTGTCAAGCCCTGAACAGAAAAACTAGCTCCAAAGTGGCTCAGGCTACC
	TGTAAACTCTGAGCCCCTTGCCCACCTGAAGCCC
	ORF Start: ATG at 2	ORF Stop: TGA at 764
	SEQ ID NO: 142	254 aa	MW at 26937.3Da
NOV34c,	MAAMRKALPRRLVGLASLRAVSTSSMGTLPKRVKIVEVGPRDGLQNERNIVSTPVKIK
CG96859-04
Protein Sequence	LIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTPNLKGFEAA
	VTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANT
	LMALQMGVSVVDSSVAGLGGCPYAQGASGNLATEDLVYMLEGLGIHTGVNLQKLLEAG
	NFICQALNRKTSSKVAQATCKL
	SEQ ID NO: 143	893 bp
NOV34d,	GATGGCAGCAATGAGGAAGGCGCTTCCGCGGCGACTGGTGGGCTTGGCGTCCCTCCGG
CG96859-05 DNA
Sequence	GCTGTCAGCACCTTATCTATGGGCACTTTACCAAAGCGGGTGAAAATTGTGGAAGTTG
	GTCCCCGAGATGGACTACAAAATGAAAAGAATATCGTATCTACTCCAGTGAAAATCAA
	GCTGATAGACATGCTTTCTGAAGCAGGACTCTCTGTTATAGAAACCACCAGCTTTGTG
	TCTCCTAAGTGGGTTCCCCAGATGGGTGACCACACTGAAGTCTTGAAGGGCATTCAGA
	AGTTTCCTGGCATCAACTACCCAGTCCTGACCCCAAATTTGAAAGGCTTCGAGGCAGC
	GGTTGCTGCTGGAGCCAAGGAAGTAGTCATCTTTGGAGCTGCCTCAGAGCTCTTCACC
	AAGAAGAACATCAATTGTTCCATAGAGGAGAGTTTTCAGAGGTTTGACGCAATCCTGA
	AGGCAGCGCAGTCAGCCAATATTTCTGTGCGGGGGTACGTCTCCTGTGCTCTTGGCTG
	CCCTTATGAAGGGAAGATCTCCCCAGCTAAAGTAGCTGAGGAAGTGCCTCTGGCTGCC
	CTGGCTGTCCACTGCCATGACACCTATGGTCAAGCCCTGGCCAACACCTTGATGGCCC
	TGCAGATGGGAGTGAGTGTCGTGGACTCTTCTGTGGCAGGACTTGGAGGCTGTCCCTA
	CGCACAGGGGGCATCAGGAAACTTGGCCACAGAAGACCTGGTCTACATGCTAGAGGGC
	TTGGGCATTCACACGGGTGTGAATCTCCAGAAGCTTCTGGAAGCTGGAAACTTTATCT
	GTCAAGCCCTGAACAGAAAAACTAGCTCCAAAGTGGCTCAGGCTACCTGTAAACTCTG
	AGCCCCTTGCCCACCTGAAGCCC
	ORF Start: ATG at 2	ORF Stop: TGA at 869
	SEQ ID NO: 144	289 aa	MW at 30531.3Da
NOV34d,	MAAMRKALPRRLVGLASLRAVSTLSMGTLPKRVKIVEVGPRDGLQNEKNIVSTPVKIK
CG96859-05
Protein Sequence	LIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTPNLKGFEAA
	VAAGAKEVVIFGAASELFTKKNINCSIEESFQRFDAILKAAQSANISVRGYVSCALGC
	PYEGKISPAKVAEEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPY
	AQGASGNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQALNRKTSSKVAQATCKL
	SEQ ID NO: 145	1353 bp
NOV34e,	CCCCAAAATTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGG
212974165 DNA
Sequence	TGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAACTAGAGAACCCACTGCTTACTGGC
	TTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGCTAGCGTTTAAACTT
	AAGCTTGGTACCGAGCTCGGATCCACCATGGCAGCAATGAGGAAGGCGCTTCCGCGGC
	GACTGGTGGGCTTGGCGTCCCTCCGGGCTGTCAGCACCTCATCTATGGGCACTTTACC
	AAAGCGGGTGAAAATTGTGGAAGTTGGTCCCCGAGATGGACTACAAAATGAAAAGAAT
	ATCGTATCTACTCCAGTGAAAATCAAGCTGATAGACATGCTTTCTGAAGCAGGACTCT
	CTGTTATAGAAACCACCAGCTTTGTGTCTCCTAAGTGGGTTCCCCAGATGGGTGACCA
	CACTGAAGTCTTGAAGGGCATTCAGAAGTTTCCTGGCATCAACTACCCAGTCCTGACC
	CCAAATTTGAAAGGCTTCGAGGCAGCGGTTGCTGCTGGAGCCAAGGAAGTAGTCATCT
	TTGGAGCTGCCTCAGAGCTCTTCACCAAGAAGAACATCAATTGTTCCATAGAGGAGAG
	TTTTCAGAGGTTTGACGCAATCCTGAAGGCAGCGCAGTCAGCCAATATTTCTGTGCGG
	GGGTACGTCTCCTGTGCTCTTGGCTGCCCTTATGAAGGGAAGATCTCCCCAGCTAAAG
	TAGCTGAGGTCACCAAGAAGTTCTACTCAATGGGCTGCTACGAGATCTCCCTGGGGGA
	CACCATTGGTGTGGGCACCCCAGGGATCATGAAAGACATGCTGTCTGCTGTCATGCAG
	GAAGTGCCTCTGGCTGCCCTGGCTGTCCACTGCCATGACACCTATGGTCAAGCCCTGG
	CCAACACCTTGATGGCCCTGCAGATGGGAGTGAGTGTCGTGGACTCTTCTGTGGCAGG
	ACTTGGAGGCTGTCCCTACGCACAGGGGGCATCAGGAAACTTGGCCACAGAAGACCTG
	GTCTACATGCTAGAGGGCTTGGGCATTCACACGGGTGTGAATCTCCAGAAGCTTCTGG
	AAGCTGGAAACTTTATCTGTCAAGCCCTGAACAGAAAAACTAGCTCCAAAGTGGCTCA
	GGCTACCTGTAAACTCTGAGCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGCTG
	ATCAGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTG
	CCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAA
	TTGCATCGCATTGTCTGAG
	ORF Start: at 145	ORF Stop: TGA at 1177
	SEQ ID NO: 146	344 aa	MW at 36362.0Da
NOV34e,	GDPSWLAFKLKLGTELGSTMAAMRKALPRRLVGLASLRAVSTSSMGTLPKRVKIVEVG
212974165 Protein
Sequence	PRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQK
	FPGINYPVLTPNLKGFEAAVAAGAKEVVIFGAASELFTKKNINCSIEESFQRFDAILK
	AAQSANISVRGYVSCALGCPYEGKISPAKVAEVTKKFYSMGCYEISLGDTIGVGTPGI
	MKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPYAQG
	ASGNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQALNRKTSSKVAQATCKL

[0498] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 34B.

TABLE 34B
Comparison of NOV34a against NOV34b through NOV34e.
	NOV34a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV34b	115 . . . 254	139/140 (99%)
	186 . . . 325	139/140 (99%)
NOV34c	1 . . . 254	253/254 (99%)
	1 . . . 254	254/254 (99%)
NOV34d	1 . . . 254	210/289 (72%)
	1 . . . 289	216/289 (74%)
NOV34e	115 . . . 254	139/140 (99%)
	205 . . . 344	139/140 (99%)

[0499] Further analysis of the NOV34a protein yielded the following properties shown in Table 34C.

TABLE 34C
Protein Sequence Properties NOV34a
PSort     0.8612 probability located in mitochondrial matrix space;
analysis: 0.5467 probability located in mitochondrial inner membrane;
          0.5467 probability located in mitochondrial intermembrane
          space; 0.5467 probability located in mitochondrial outer
          membrane
SignalP   Cleavage site between residues 25 and 26
analysis:

[0500] A search of the NOV34a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 34D.

TABLE 34D
Geneseq Results for NOV34a
		NOV34a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU75774	Human 3-hydroxy-3-	115 . . . 254	138/140 (98%)	2e−74
	methylglutaryl coenzyme A	186 . . . 325	138/140 (98%)
	lyase (HMGCL) protein -
	Homo sapiens, 325 aa.
	[WO200198315-A2, 27 DEC. 2001]
AAU01613	Gene #24 human secreted	115 . . . 250	111/136 (81%)	7e−61
	protein homologous amino	157 . . . 292	126/136 (92%)
	acid sequence - Homo
	sapiens, 293 aa.
	[WO200123547-A1, 05 APR. 2001]
AAU01614	Human secreted protein	117 . . . 251	102/135 (75%)	1e−56
	encoded by gene #24 - Homo	159 . . . 293	123/135 (90%)
	sapiens, 293 aa.
	[WO200123547-A1, 05 APR. 2001]
AAB53631	Human colon cancer antigen	4 . . . 115	102/112 (91%)	4e−51
	protein sequence SEQ ID	16 . . . 127	102/112 (91%)
	NO: 1171 - Homo sapiens, 130 aa.
	[WO200055351-A1, 21 SEP. 2000]
AAE19938	Wheat HMG-CoA lyase -	115 . . . 254	96/140 (68%)	2e−50
	Triticum aestivum, 157 aa.	11 . . . 150	114/140 (80%)
	[U.S. Pat. No. 6348339-B1, 19 FEB. 2002]

[0501] In a BLAST search of public sequence datbases, the NOV34a protein was found to have homology to the proteins shown in the BLASTP data in Table 34E.

TABLE 34E
Public BLASTP Results for NOV34a
		NOV34a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96FP8	3-hydroxymethyl-3-methylglutaryl-	115 . . . 254	139/140 (99%)	2e−74
	coenzyme A lyase	186 . . . 325	139/140 (99%)
	(Hydroxymethylglutaricaciduria) - Homo
	sapiens (Human), 325 aa.
Q96TG6	DJ886K2.2	115 . . . 254	139/140 (99%)	2e−74
	(HMGCL(hydroxymethylglutaryl-CoA	166 . . . 305	139/140 (99%)
	lyase)) - Homo sapiens (Human), 305 aa
	(fragment).
P35914	Hydroxymethylglutaryl-CoA lyase,	115 . . . 254	138/140 (98%)	6e−74
	mitochondrial precursor (EC 4.1.3.4)	186 . . . 325	138/140 (98%)
	(HMG-CoA lyase) (HL) (3-hydroxy-3-
	methylglutarate−CoA lyase) - Homo
	sapiens (Human), 325 aa.
Q8QZS6	3-hydroxy-3-methylglutaryl-coenzyme A	115 . . . 254	128/140 (91%)	5e−69
	lyase - Mus musculus (Mouse), 325 aa.	186 . . . 325	134/140 (95%)
P97519	Hydroxymethylglutaryl-CoA lyase,	115 . . . 254	128/140 (91%)	5e−69
	mitochondrial precursor (EC 4.1.3.4)	186 . . . 325	135/140 (96%)
	(HMG-CoA lyase) (HL) (3-hydroxy-3-
	methylglutarate−CoA lyase) - Rattus
	norvegicus (Rat), 325 aa.

[0502] PFam analysis predicts that the NOV34a protein contains the domains shown in the Table 34F.

TABLE 34F
Domain Analysis of NOV34a
		Identities/
	NOV34a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
HMGL-like	41 . . . 247	79/307 (26%)	4e−56
		184/307 (60%)

Example 35

[0503] The NOV35 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 35A.

TABLE 35A
NOV35 Sequence Analysis
	SEQ ID NO: 147	2579 bp
NOV35a,	TTGCCTCTGCCATGCTGGGCCCTGCTGTCCTGGGCCTCAGCCTCTGGGCTCTCCTGCA
CG98082-01 DNA
Sequence	CCCTGGGACGGGGGCCCCATTGTGCCTGTCACAGCAACTTAGGATGAAGGGGGACTAC
	GTGCTGGGGGGGCTGTTCCCCCTGGGCGAGGCCGAGGAGGCTGGCCTCCGCAGCCGGA
	CACGGCCCAGCAGCCCTGTGTGCACCAGGTTCTCCTCAAACGGCCTGCTCTGGGCACT
	GGCCATGAAAATGGCCGTGGAGGAGATCAACAACAAGTCGGATCTGCTGCCCGGGCTG
	CGCCTGGGCTACGACCTCTTTGATACGTGCTCGGAGCCTGTGGTGGCCATGAAGCCCA
	GCCTCATGTTCCTGGCCAAGGCAGGCAGCCGCGACATCGCCGCCTACTGCAACTACAC
	GCAGTACCAGCCCCGTGTGCTGGCTGTCATCGGGCCCCACTCGTCAGAGCTCGCCATG
	GTCACCGGCAAGTTCTTCAGCTTCTTCCTCATGCCCCAGGTCAGCTACGGTGCTAGCA
	TGGAGCTGCTGAGCGCCCGGGAGACCTTCCCCTCCTTCTTCCGCACCGTGCCCAGCGA
	CCGTGTGCAGCTGACGGCCGCCGCGGAGCTGCTGCAGGAGTTCGGCTGGAACTGGGTG
	GCCGCCCTGGGCAGCGACGACGAGTACGGCCGGCAGGGCCTGAGCATCTTCTCGGCCC
	TGGCCGCGGCACGCGGCATCTGCATCGCGCACGAGGGCCTGGTGCCGCTGCCCCGTGC
	CGATGACTCGCGGCTGGGGAAGGTGCAGGACGTCCTGCACCAGGTGAACCAGAGCAGC
	GTGCAGGTGGTGCTGCTGTTCGCCTCCGTGCACGCCGCCCACGCCCTCTTCAACTACA
	GCATCAGCAGCAGGCTCTCGCCCAAGGTGTGGGTGGCCAGCGAGGCCTGGCTGACCTC
	TGACCTGGTCATGGGGCTGCCCGGCATGGCCCAGATGGGCACGGTGCTTGGCTTCCTC
	CAGAGGGGTGCCCAGCTGCACGAGTTCCCCCAGTACGTGAAGACGCACCTGGCCCTGG
	CCACCGACCCGGCCTTCTGCTCTGCCCTGGGCGAGAGGGAGCAGGGTCTGGAGGAGGA
	CGTGGTGGGCCAGCGCTGCCCGCAGTGTGACTGCATCACGCTGCAGAACGTGAGCGCA
	GGGCTAAATCACCACCAGACGTTCTCTGTCTACGCAGCTGTGTATAGCGTGGCCCAGG
	CCCTGCACAACACTCTTCAGTGCAACGCCTCAGGCTGCCCCGCGCAGGACCCCGTGAA
	GCCCTGGCAGCTCCTGGAGAACATGTACAACCTGACCTTCCACGTGGGCGGGCTGCCG
	CTGCGGTTCGACAGCAGCGGAAACGTGGACATGGAGTACGACCTGAAGCTGTGGGTGT
	GGCAGGGCTCAGTGCCCAGGCTCCACGACGTGGGCAGGTTCAACGGCAGCCTCAGGAC
	AGAGCGCCTGAAGATCCGCTGGCACACGTCTGACAACCAGGTGCCCGTGTCCCGGTGC
	TCGCGGCAGTGCCAGGAGGGCCAGGTGCGCCGGGTCAAGGGGTTCCACTCCTGCTGCT
	ACGACTGTGTGGACTGCGAGGCGGGCAGCTACCGGCAAAACCCAGACGACATCGCCTG
	CACCTTTTGTGGCCAGGATGAGTGGTCCCCGGAGCGAAGCACACGCTGCTTCCGCCGC
	AGGTCTCGGTTCCTGGCATGGGGCGAGCCGGCTGTGCTGCTGCTGCTCCTGCTGCTGA
	GCCTGGCGCTGGGCCTTGTGCTGGCTGCTTTGGGGCTGTTCGTTCACCATCGGGACAG
	CCCACTGGTTCAGGCCTCGGGGGGGCCCCTGGCCTGCTTTGGCCTGGTGTGCCTGGGC
	CTGGTCTGCCTCAGCGTCCTCCTGTTCCCTGGCCAGCCCAGCCCTGCCCGATGCCTGG
	CCCAGCAGCCCTTGTCCCACCTCCCGCTCACGGGCTGCCTGAGCACACTCTTCCTGCA
	GGCGGCCGAGATCTTCGTGGAGTCAGAACTGCCTCTGAGCTGGGCAGACCGGCTGAGT
	GGCTGCCTGCGGGGGCCCTGGGCCTGGCTGGTGGTGCTGCTGGCCATGCTGGTGGAGG
	TCGCACTGTGCACCTGGTACCTGGTGGCCTTCCCGCCGGAGGTGGTGACGGACTGGCA
	CATGCTGCCCACGGAGGCGCTGGTGCACTGCCGCACACGCTCCTGGGTCAGCTTCGGC
	CTAGCGCACGCCACCAATGCCACGCTGGCCTTTCTCTGCTTCCTGGGCACTTTCCTGG
	TGCGGAGCCAGCCGGGCTGCTACAACCGTGCCCGTGGCCTCACCTTTGCCATGCTGGC
	CTACTTCATCACCTGGGTCTCCTTTGTGCCCCTCCTGGCCAATGTGCAGGTGGTCCTC
	AGGCCCGCCGTGCAGATGGGCGCCCTCCTGCTCTGTGTCCTGGGCATCCTGGCTGCCT
	TCCACCTGCCCAGGTGTTACCTGCTCATGCGGCAGCCAGGGCTCAACACCCCCGAGTT
	CTTCCTGGGAGGGGGCCCTGGGGATGCCCAAGGCCAGAATGACGGGAACACAGGAAAT
	CAGGGGAAACATGAGTGACCCAACCCT
	ORF Start: ATG at 12	ORF Stop: TGA at 2568
	SEQ ID NO: 148	852 aa	MW at 93355.9Da
NOV35a,	MLGPAVLGLSLWALLHPGTGAPLCLSQQLRMKGDYVLGGLFPLGEAEEAGLRSRTRPS
CG98082-01
Protein Sequence	SPVCTRFSSNGLLWALAMKMAVEEINNKSDLLPGLRLGYDLFDTCSEPVVAMKPSLMF
	LAKAGSRDIAAYCNYTQYQPRVLAVIGPHSSELAMVTGKFFSFFLMPQVSYGASMELL
	SARETFPSFFRTVPSDRVQLTAAAELLQEFGWNWVAALGSDDEYGRQGLSIFSALAAA
	RGICIAHEGLVPLPRADDSRLGKVQDVLHQVNQSSVQVVLLFASVHAAHALFNYSISS
	RLSPKVWVASEAWLTSDLVMGLPGMAQMGTVLGFLQRGAQLHEFPQYVKTHLALATDP
	AFCSALGEREQGLEEDVVGQRCPQCDCITLQNVSAGLNHHQTFSVYAAVYSVAQALHN
	TLQCNASGCPAQDPVKPWQLLENMYNLTFHVGGLPLRFDSSGNVDMEYDLKLWVWQGS
	VPRLHDVGRFNGSLRTERLKIRWHTSDNQVPVSRCSRQCQEGQVRRVKGFHSCCYDCV
	DCEAGSYRQNPDDIACTFCGQDEWSPERSTRCFRRRSRFLAWGEPAVLLLLLLLSLAL
	GLVLAALGLFVHHRDSPLVQASGGPLACFGLVCLGLVCLSVLLFPGQPSPARCLAQQP
	LSHLPLTGCLSTLFLQAAEIFVESELPLSWADRLSGCLRGPWAWLVVLLAMLVEVALC
	TWYLVAFPPEVVTDWHMLPTEALVHCRTRSWVSFGLAHATNATLAFLCFLGTFLVRSQ
	PGCYNRARGLTFAMLAYFITWVSFVPLLANVQVVLRPAVQMGALLLCVLGILAAFHLP
	RCYLLMRQPGLNTPEFFLGGGPGDAQGQNDGNTGNQGKHE

[0504] Further analysis of the NOV35a protein yielded the following properties shown in Table 35B.

TABLE 35B
Protein Sequence Properties NOV35a
PSort     0.6000 probability located in plasma membrane; 0.4000
analysis: probability located in Golgi body; 0.3000 probability
          located in endoplasmic reticulum (membrane); 0.3000
          probability located in microbody (peroxisome)
SignalP   Cleavage site between residues 21 and 22
analysis:

[0505] A search of the NOV35a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 35C.

TABLE 35C
Geneseq Results for NOV35a
		NOV35a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU78587	Human AXOR79 protein - Homo	1 . . . 852	850/852 (99%)	0.0
	sapiens, 852 aa. [GB2364058-A,	1 . . . 852	850/852 (99%)
	16 JAN. 2002]
AAU08996	Human G protein-coupled receptor,	1 . . . 852	850/852 (99%)	0.0
	GPCR, 50289 - Homo sapiens, 852	1 . . . 852	850/852 (99%)
	aa. [WO200164882-A2, 07 SEP. 2001]
AAU73184	Human SAC1 polypeptide - Homo	1 . . . 852	849/852 (99%)	0.0
	sapiens, 852 aa. [WO200183749-A2,	1 . . . 852	850/852 (99%)
	08 NOV. 2001]
AAE10366	Human taste−cell-specific G protein-	1 . . . 852	848/852 (99%)	0.0
	coupled receptor, hT1R3 protein -	I . . . 850	848/852 (99%)
	Homo sapiens, 850 aa.
	[WO200166563-A2, 13 SEP. 2001]
ABB77318	Human G-protein coupled receptor	1 . . . 852	850/863 (98%)	0.0
	SEQ ID NO 2 - Homo sapiens, 863	1 . . . 863	850/863 (98%)
	aa. [WO200198323-A2, 27 DEC. 2001]

[0506] In a BLAST search of public sequence datbases, the NOV35a protein was found to have homology to the proteins shown in the BLASTP data in Table 35D.

TABLE 35D
Public BLASTP Results for NOV35a
		NOV35a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
CAC88308	Sequence 13 fom Patent	1 . . . 852	850/852 (99%)	0.0
	WO0164882 - Homo sapiens	1 . . . 852	850/852 (99%)
	(Human), 852 aa.
Q923K1	Sweet taste receptor T1R3 - Rattus	1 . . . 847	624/855 (72%)	0.0
	norvegicus (Rat), 858 aa.	1 . . . 849	698/855 (80%)
Q91VA4	Putative taste receptor (Candidate	5 . . . 852	622/857 (72%)	0.0
	taste receptor T1R3) (Putative sweet	5 . . . 858	690/857 (79%)
	taste receptor type 1 member 3) - Mus
	musculus (Mouse), 858 aa.
Q925A4	Putative taste receptor - Mus	5 . . . 843	619/847 (73%)	0.0
	musculus (Mouse), 858 aa.	5 . . . 848	685/847 (80%)
Q925D9	Putative sweet taste receptor family 1	5 . . . 843	619/847 (73%)	0.0
	member 3 - Mus musculus (Mouse),	5 . . . 848	686/847 (80%)
	858 aa.

[0507] PFam analysis predicts that the NOV35a protein contains the domains shown in the Table 35E.

TABLE 35E
Domain Analysis of NOV35a
		Identities/
	NOV35a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
ANF_receptor	61 . . . 276	62/235 (26%)	1.1e−56
		160/235 (68%)
ANF_receptor	393 . . . 456	26/69 (38%)	3.3e−07
		51/69 (74%)
7tm_3	569 . . . 824	79/285 (28%)	8.9e−12
		164/285 (58%)

Example 36

[0508] The NOV36 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 36A.

TABLE 36A
NOV36 Sequence Analysis
	SEQ ID NO: 149	596 bp
NOV36a,	ACCTCCTCCTACTGTTCAAGTACAGGGGCCTGGTCCGCAAAGGGAAGAAAAGCAAAAG
CG98102-04 DNA
Sequence	ACGAAAATGGCTAAATATGAATACATGGAAGAACAAGTAATCTTAACTGAAAAAGATC
	TGCTAGAAGATGGTTTTGGAGAGCACCCCTTTTACCACTGCCTGGTTGCAGAAGTGCC
	GAAAGAGCACTGGACTCCGGAAGGACACAGCATTGTTGGTTTTGCCATGTACTATTTT
	ACCTATGACCCGTGGATTGGCAAGTTATTGTATCTTGAGGACTTCTTCGTGATGAGTG
	ATTATAGAGGCTTTGGCATAGGATCAGAAATTCTGAAGAATCTAAGCCAGGTTGCAAT
	GAGGTGTCGCTGCAGCAGCATGCACTTCTTGGTAGCAGAATGGAATGAACCATCCATC
	AACTTCTATAAAAGAAGAGGTGCTTCTGATCTGTCCAGTGAAGAGGGTTGGAGACTGT
	TCAAGATCGACAAGGAGTACTTGCTAAAAATGGCAACAGAGGAGTGAGGAGTGCTGCT
	GTAGATGACAACCTCCATTCTATTTTAGAATAAATTCCCAACTTCTCTTGCTTTCTAT
	GCTGTTTGTAGTGAAA
	ORF Start: ATG at 65	ORF Stop: TGA at 509
	SEQ ID NO: 150	148 aa	MW at 17497.8Da
NOV36a,	MAKYEYMEEQVILTEKDLLEDGFGEHPFYHCLVAEVPKEHWTPEGHSIVGFANYYFTY
CG98102-04
Protein Sequence	DPWIGKLLYLEDFFVMSDYRGFGIGSEILKNLSQVAMRCRCSSMHFLVAEWNEPSINF
	YKRRGASDLSSEEGWRLFKIDKEYLLKMATEE

[0509] Further analysis of the NOV36a protein yielded the following properties shown in Table 36B.

TABLE 36B
Protein Sequence Properties NOV36a
PSort     0.6400 probability located in microbody (peroxisome); 0.4500
analysis: probability located in cytoplasm; 0.1000 probability located
          in mitochondrial matrix space; 0.1000 probability located in
          lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0510] A search of the NOV36a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 36C.

TABLE 36C
Geneseq Results for NOV36a
		NOV36a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB57094	Mouose ischaemic condition related	1 . . . 148	143/148 (96%)	3e−84
	protein sequence SEQ ID NO: 207 -	24 . . . 171	146/148 (98%)
	Mus musculus, 171 aa.
	[WO200188188-A2, 22 NOV. 2001]
AAU30048	Novel human secreted protein #539 -	1 . . . 135	122/138 (88%)	2e−67
	Homo sapiens, 218 aa.	58 . . . 195	128/138 (92%)
	[WO200179449-A2, 25 OCT. 2001]
AAB44145	Human cancer associated protein	19 . . . 104	85/86 (98%)	2e−48
	sequence SEQ ID NO: 1590 - Homo	1 . . . 86	85/86 (98%)
	sapiens, 92 aa. [WO200055350-A1, 21 SEP. 2000]
AAB82049	Human spermidine/spermine acetyl	1 . . . 132	91/140 (65%)	1e−42
	transferase protein isomer - Homo	49 . . . 184	101/140 (72%)
	sapiens, 192 aa. [CN1278003-A,
	27 DEC. 2000]
AAW58394	Human spermidine/spermine N1-	1 . . . 145	63/145 (43%)	4e−33
	acetyltransferase - Homo sapiens, 170	24 . . . 168	94/145 (64%)
	aa. [WO9818938-A1, 07 MAY 1998]

[0511] In a BLAST search of public sequence datbases, the MPV36a protein was found to have homology to the proteins shown in the BLASTP data in Table 36D.

TABLE 36D
Public BLASTP Results for NOV36a
		NOV36a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P21673	Diamine acetyltransferase (EC	1 . . . 148	147/148 (99%)	8e−86
	2.3.1.57) (Spermidine/spermine N(1)-	24 . . . 171	148/148 (99%)
	acetyltransferase) (SSAT) (Putrescine
	acetyltransferase) - Homo sapiens
	(Human), 171 aa.
JH0783	diamine N-acetyltransferase (EC	1 . . . 148	146/148 (98%)	2e−85
	2.3.1.57) - human, 171 aa.	24 . . . 171	148/148 (99%)
P49431	Spermidine/spermine N(1)-	1 . . . 148	144/148 (97%)	1e−84
	acetyltransferase (EC 2.3.1.57)	24 . . . 171	147/148 (99%)
	(Diamine acetyltransferase) (SSAT)
	(Putrescine acetyltransferase) - Mus
	saxicola (Spiny mouse), 171 aa.
Q9JHW6	Spermidine/spermine N1-	1 . . . 148	142/148 (95%)	4e−84
	acetyltransferase - Cricetulus griseus	24 . . . 171	147/148 (98%)
	(Chinese hamster), 171 aa.
P48026	Diamine acetyltransferase (EC	1 . . . 148	143/148 (96%)	7e−84
	2.3.1.57) (Spermidine/spermine N(1)-	24 . . . 171	146/148 (98%)
	acetyltransferase) (SSAT) (Putrescine
	acetyltransferase) - Mus musculus
	(Mouse), 171 aa.

[0512] PFam analysis predicts that the NOV36a protein contains the domains shown in the Table 36E.

TABLE 36E
Domain Analysis of NOV36a
		Identities/
	NOV36a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
Acetyltransf	40 . . . 123	23/85 (27%)	1.6e−16
		59/85 (69%)

Example 37

[0513] The NOV37 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 37A.

TABLE 37A
NOV37 Sequence Analysis
	SEQ ID NO: 151	610 bp
NOV37a,	CATGAAACAGCAGCAGTGGTGTGGGATGACTGCCAAAATGGGCACCGTGTTGTCAGGGGT
CG122863-01
DNA Sequence	CTTCACCATCATGGCCGTAGACATGTATCTCATCTTTGAACAGAAGCACCTAGGGAATGG
	CAGTTGCACTGAGATCACACCAAAGTACAGGGGTGCAAGTAACATCATAAATAACTTCAT
	CATCTGCTGGAGTTTTAAAATCGTCCTCTTCCTGTCTTTCATCACCATCCTCATCAGCTG
	CTTCCTCCTGTACTCAGTGTATGCCCAGATCTTCAGGGGCCTGGTCATCTACATTGTCTG
	GATTTTTTTCTATGAAACTGCAAACGTCGTAATACAAATCCTCACCAACAATGACTTTGA
	CATTAAAGAGGTCAGAATCATGCGCTGGTTTGGCTTGGTGTCTCGTACAGTCATGCACTG
	TTTCTGGATGTTCTTTGTCATCAACTATGCCCACATAACCTACAAAAACCGGAGCCAGGG
	CAATATAATTTCCTACAAGAGACGAATTTCTACAGCGGAGATTCTCCACAGCAGAAATAA
	AAGATTATCAATTTCGAGTGGGTTCAGTGGCTCACACCTGGAATCCCAGTACTTTGAGAG
	GCAGAGGTAG
	ORF Start: ATG at 2	ORF Stop: TAG at 608
	SEQ ID NO: 152	919 aa	MW
NOV37a,	MKQQQWCGMTAKMGTVLSGVFTIMAVDMYLIFEQKHLGNGSCTEITPKYRGASNIINNFI
CG122863-01
Protein Sequence	ICWSFKIVLFLSFITILISCFLLYSVYAQIFRGLVIYIVWIFFYETANVVIQILTNNDFD
	IKEVRIMRWFGLVSRTVMHCFWMFFVINYAHITYKNRSQGNIISYKRRISTAEILHSRNK
	RLSISSGFSGSHLESQYFERQR
	SEQ ID NO: 153	610 bp
NOV37b,	CATGAAACAGCAGCAGTGGTGTGGGATGACTGCCAAAATGGGCACCGTGTTGTCAGGGGT
CG122863-02
DNA Sequence	CTTCACCATCATGGCCGTAGACATGTATCTCATCTTTGAACAGAAGCACCTAGGGAATGG
	CAGTTGCACTGAGATCACACCAAAGTACAGGGGTGCAAGTAACATCATAAATAACTTCAT
	CATCTGCTGGAGTTTTAAAATCGTCCTCTTCCTGTCTTTCATCACCATCCTCATCAGCTG
	CTTCCTCCTGTACTCAGTGTATGCCCAGATCTTCAGGGGCCTGGTCATCTACATTGTCTG
	GATTTTTTTCTATGAAACTGCAAACGTCGTAATACAAATCCTCACCAACAATGACTTTGA
	CATTAAAGAGGTCAGAATCATGCGCTGGTTTGGCTTGGTGTCTCGTACAGTCATGCACTG
	TTTCTGGATGTTCTTTGTCATCAACTATGCCCACATAACCTACAAAAACCGGAGCCAGGG
	CAATATAATTTCCTACAAGAGACGAATTTCTACAGCGGAGATTCTCCACAGCAGAAATAA
	AAGATTATCAATTTCGAGTGGGTTCAGTGGCTCACACCTGGAATCCCAGTACTTTGAGAG
	GCAGAGGTAG
	ORF Start: ATG at 2	ORF Stop: TAG at 608
	SEQ ID NO: 154	202 aa	MW
NOV37b,	MKQQQWCGMTAKMGTVLSGVFTIMAVDMYLIFEQKHLGNGSCTEITPKYRGASNIINNFI
CG122863-02
Protein Sequence	ICWSFKIVLFLSFITILISCFLLYSVYAQIFRGLVIYIVWIFFYETANVVIQILTNNDFD
	IKEVRIMRWFGLVSRTVMHCFWMFFVINYAHITYKNRSQGNIISYKRRISTAEILHSRNK
	RLSISSGFSGSHLESQYFERQR

[0514] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 32B.

TABLE 37B
Comparison of NOV37a against NOV37b.
Protein	NOV37a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV37b	1 . . . 202	202/202 (100%)

[0515] Further analysis of the NOV37a protein yielded the following properties shown in Table 37C.

TABLE 37C
Protein Sequence Properties NOV37a
PSort     0.6000 probability located in the plasma membrane; 0.4000
analysis: probability located in the Golgi body; 0.3000 probability
          located in the endoplasmic reticulum (membrane); 0.3000
          probability located in the microbody (peroxisome)
SignalP   Cleavage site between residues 25 and 26
analysis:

[0516] A search of the NOV37a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 37D.

TABLE 37D
Geneseq Results for NOV37a
			Identities/
			Similari-
		NOV37a	ties
	Protein/	Residues/	for the
Geneseq	Organism/Length	Match	Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAE10587	Human macrophage-	1/123	123/123	7.8e−63
	expressed protein	1 . . . 123	(100%)
	#12 - Homo		123/123
	sapiens, 127 aa.		(100%)
	WO200164839-A2.
	07 SEP. 2001.
AAM06487	Human foetal	47 . . . 81	14/35	0.30
	protein, SEQ ID NO:	10 . . . 44	(40%)
	218 - Homo		24/35
	sapiens, 54 aa.		(68%)
	WO200155339-A2;
	02 AUG. 2001.
AAM06868	Human foetal	47 . . . 81	14/35	0.30
	protein, SEQ ID NO:	10 . . . 44	(40%)
	1076 - Homo		24/35
	sapiens, 54 aa.		(68%)
	WO200155339-A2;
	02 AUG. 2001.
AAO12651	Human polypeptide	58 . . . 104	17/52	0.45
	SEQ ID NO 26543 -	32 . . . 83	(32%)
	Homo sapiens, 89 aa.		29/52
	WO200164835-A2;		(55%)
	07 SEP. 2001.

[0517] In a BLAST search of public sequence datbases, the NOV37a protein was found to have homology to the proteins shown in the BLASTP data in Table 37E.

TABLE 37E
Public BLASTP Results for NOV37a
			Identities/
			Similari-
		NOV37a	ties
Protein		Residues/	for the
Accession	Protein/	Match	Matched	Expect
Number	Organizm/Length	Residues	Portion	Value
Q8TE60	ADAMTS18 protein -	1 . . . 858	840/858	0.0
	Homo sapiens	1 . . . 852	(97%)
	(Human), 1081 aa.		844/858
			(97%)
Q8TC54	Similar to RIKEN	1 . . . 202	202/202	6.5e−
	cDNA 4933413N12	1 . . . 202	(100%)	107
	gene - Homo sapiens		202/202
	(Human), 211 aa.		(100%)
Q9D446	4933413N12Rik	1 . . . 194	106/194	1.0e−53
	protein -	1 . . . 189	(54%)
	Mus musculus		140/194
	(Mouse), 189 aa.		(72%)
AAH29657	Similar to	9 . . . 168	50/160	4.4e−14
	hypothetical gene	1 . . . 159	(31%)
	supported by		83/160
	BC026012		(51%)
	Homo sapiens
	(Human), 170 aa.
Q9EN34	AMV012 -	57 . . . 104	14/48	0.24
	Amsacta moorei		13-59	(29%)
	entomopoxvirus		28/48
	(AmEPV), 86 aa.		(58%)

[0518] PFam analysis predicts that the NOV37a protein contains the domains shown in the Table 37F.

TABLE 37F
Domain Analysis of NOV37a
		Identities/
	NOV37a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value

Example B

Sequencing Methodology and Identification of NOVX Clones

[0519] 1. GeneCalling™ Technology: This is a proprietary method of performing differential gene expression profiling between two or more samples developed at CuraGen and described by Shimkets, et al., “Gene expression analysis by transcript profiling coupled to a gene database query” Nature Biotechnology 17:198-803 (1999). cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then digested with up to as many as 120 pairs of restriction enzymes and pairs of linker-adaptors specific for each pair of restriction enzymes were ligated to the appropriate end. The restriction digestion generates a mixture of unique cDNA gene fragments. Limited PCR amplification is performed with primers homologous to the linker adapter sequence where one primer is biotinylated and the other is fluorescently labeled. The doubly labeled material is isolated and the fluorescently labeled single strand is resolved by capillary gel electrophoresis. A computer algorithm compares the electropherograms from an experimental and control group for each of the restriction digestions. This and additional sequence-derived information is used to predict the identity of each differentially expressed gene fragment using a variety of genetic databases. The identity of the gene fragment is confirmed by additional, gene-specific competitive PCR or by isolation and sequencing of the gene fragment.

[0520] 2. SeqCalling™ Technology: cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then sequenced using CuraGen's proprietary SeqCalling technology. Sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation's database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.

[0521] 3. PathCalling™ Technology: The NOVX nucleic acid sequences are derived by laboratory screening of cDNA library by the two-hybrid approach. cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, are sequenced. In silico prediction was based on sequences available in CuraGen Corporation's proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.

[0522] The laboratory screening was performed using the methods summarized below:

[0523] cDNA libraries were derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then directionally cloned into the appropriate two-hybrid vector (Gal4-activation domain (Gal4-AD) fusion). Such cDNA libraries as well as commercially available cDNA libraries from Clontech (Palo Alto, Calif.) were then transferred from E.coli into a CuraGen Corporation proprietary yeast strain (disclosed in U.S. Pat. Nos. 6,057,101 and 6,083,693, incorporated herein by reference in their entireties).

[0524] Gal4-binding domain (Gal4-BD) fusions of a CuraGen Corportion proprietary library of human sequences was used to screen multiple Gal4-AD fusion cDNA libraries resulting in the selection of yeast hybrid diploids in each of which the Gal4-AD fusion contains an individual cDNA. Each sample was amplified using the polymerase chain reaction (PCR) using non-specific primers at the cDNA insert boundaries. Such PCR product was sequenced; sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation's database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.

[0525] Physical clone: the cDNA fragment derived by the screening procedure, covering the entire open reading frame is, as a recombinant DNA, cloned into pACT2 plasmid (Clontech) used to make the cDNA library. The recombinant plasmid is inserted into the host and selected by the yeast hybrid diploid generated during the screening procedure by the mating of both CuraGen Corporation proprietary yeast strains N106′ and YULH (U.S. Pat. Nos. 6,057,101 and 6,083,693).

[0526] 4. RACE: Techniques based on the polymerase chain reaction such as rapid amplification of cDNA ends (RACE), were used to isolate or complete the predicted sequence of the cDNA of the invention. Usually multiple clones were sequenced from one or more human samples to derive the sequences for fragments. Various human tissue samples from different donors were used for the RACE reaction. The sequences derived from these procedures were included in the SeqCalling Assembly process described in preceding paragraphs.

[0527] 5. Exon Linking: The NOVX target sequences identified in the present invention were subjected to the exon linking process to confirm the sequence. PCR primers were designed by starting at the most upstream sequence available, for the forward primer, and at the most downstream sequence available for the reverse primer. In each case, the sequence was examined, walking inward from the respective termini toward the coding sequence, until a suitable sequence that is either unique or highly selective was encountered, or, in the case of the reverse primer, until the stop codon was reached. Such primers were designed based on in silico predictions for the full length cDNA, part (one or more exons) of the DNA or protein sequence of the target sequence, or by translated homology of the predicted exons to closely related human sequences from other species. These primers were then employed in PCR amplification based on the following pool of human cDNAs: adrenal gland, bone marrow, brain—amygdala, brain—cerebellum, brain—hippocampus, brain—substantia nigra, brain—thalamus, brain—whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma—Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus. Usually the resulting amplicons were gel purified, cloned and sequenced to high redundancy. The PCR product derived from exon linking was cloned into the pCR2.1 vector from Invitrogen. The resulting bacterial clone has an insert covering the entire open reading frame cloned into the pCR2.1 vector. The resulting sequences from all clones were assembled with themselves, with other fragments in CuraGen Corporation's database and with public ESTs. Fragments and ESTs were included as components for an assembly when the extent of their identity with another component of the assembly was at least 95% over 50 bp. In addition, sequence traces were evaluated manually and edited for corrections if appropriate. These procedures provide the sequence reported herein.

[0528] 6. Physical Clone: Exons were predicted by homology and the intron/exon boundaries were determined using standard genetic rules. Exons were further selected and refined by means of similarity determination using multiple BLAST (for example, tBlastN, BlastX, and BlastN) searches, and, in some instances, GeneScan and Grail. Expressed sequences from both public and proprietary databases were also added when available to further define and complete the gene sequence. The DNA sequence was then manually corrected for apparent inconsistencies thereby obtaining the sequences encoding the full-length protein.

[0529] The PCR product derived by exon linking, covering the entire open reading frame, was cloned into the pCR2.1 vector from Invitrogen to provide clones used for expression and screening purposes.

[0530] Molecular Cloning of CG56735-02::Mat Reprolysin (295-498)

[0531] The cDNA coding for a domain of CG56735-02 from residue 295-498 was targeted for “in-frame” cloning by PCR. The PCR template is based on human cDNA(s).

[0532] The following oligonucleotide primers were used to clone the target cDNA sequence:

			Start
Primers	Sequences	Length	Position	SEQ ID No
F3	5′-GGATCCGTGGAAACCCTCGTGGTGGCAGACAAG-3′	33		360
R3	5′-CTCGAGGGGCTCATCCACTAGACACCCCGCCTGAGG-3′	36		361

[0533] For downstream cloning purposes, the forward primer includes an in-frame BamH I restriction site and the reverse primer contains an in-frame XhoI restriction site.

[0534] Two parallel PCR reactions were set up using a total of 0.5-1.0 ng human pooled cDNAs as template for each reaction. The pool is composed of 5 micrograms of each of the following human tissue cDNAs: adrenal gland, whole brain, amygdala, cerebellum, thalamus, bone marrow, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, liver, lymphoma, Burkitt's Raji cell line, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary, gland, skeletal muscle, small Intestine, spleen, stomach, thyroid, trachea, uterus.

[0535] When the tissue of expression is known and available, the second PCR was performed using the above primers and 0.5 ng-1.0 ng of one of the following human tissue cDNAs: skeleton muscle, testis, mammary gland, adrenal gland, ovary, colon, normal cerebellum; normal adipose, normal skin, bone marrow, brain amygdala, brain hippocampus, brain substantia nigra, brain thalamus, thyroid, fetal lung, fetal liver, fetal brain, kidney, heart, spleen, uterus, pituitary gland, lymph node, salivary gland, small intestine, prostate, placenta, spinal cord, peripheral blood, trachea, stomach, pancreas, hypothalamus.

[0536] The reaction mixtures contained 2 microliters of each of the primers (original concentration: 5 pmol/ul), 1 microliter of 10 mM dNTP (Clontech Laboratories, Palo Alto Calif.) and 1 microliter of 50×Advantage-HF 2 polymerase (Clontech Laboratories) in 50 microliter-reaction volume. The following reaction conditions were used:

PCR condition 1:
a)	96° C.	3 minutes
b)	96° C.	30 seconds denaturation
c)	60° C.	30 seconds, primer annealing
d)	72° C.	6 minutes extension
Repeat steps b-d 15 times
e)	96° C.	15 seconds denaturation
f)	60° C.	30 seconds, primer annealing
g)	72° C.	6 minutes extension
Repeat steps e-g 29 times
e)	72° C.	10 minutes final extension
PCR condition 2:
a)	96° C.	3 minutes
b)	96° C.	15 seconds denaturation
c)	76° C.	30 seconds, primer annealing, reducing the temperature
		by 1° C. per cycle
d)	72° C.	4 minutes extension
Repeat steps b-d 34 times
e)	72° C.	10 minutes final extension

[0537] An amplified product was detected by agarose gel electrophoresis. The fragment was gel-purified and ligated into the pCR2.1 vector (Invitrogen, Carlsbad, Calif.) following the manufacturer's recommendation. Twelve clones per PCR reaction were picked and sequenced. The inserts were sequenced using vector-specific M13 Forward and M13 Reverse primers and the following gene-specific primers:

Primers	Sequences	Length	Start Position	SEQ ID No
SF1	GAATAGTTTTTGTCAATGGCAGTCT	25		362
SF2	GTGACACTCTAGGGTTTGCCCC	22		363
SR1	ATTCAGAGACTGGTCTGCATGATGG	25		364
SR2	ACATGGTTCATTCTTCCAAGAACAAATATCA	31		365

[0538] The insert assembly 174124733 was found to encode an open reading frame between residues 295 and 498 of the target sequence of CG56735-02. The cloned insert is 99% identical to the original sequence. It differs from the original sequence at 1 amino acid position and 1 nucleotide position. The alignment with CG56735-02 is displayed in a ClustalW below. Note that differing amino acids have a white or grey background, and deleted/inserted amino acids can be detected by a dashed line in the sequence that does not code at that position.

Example C

Quantitative Expression Analysis of Clones in Various Cells and Tissues

[0539] The quantitative expression of various clones was assessed using microtiter plates containing RNA samples from a variety of normal and pathology-derived cells, cell lines and tissues using real time quantitative PCR (RTQ PCR). RTQ PCR was performed on an Applied Biosystems ABI PRISM® 7700 or an ABI PRISM® 7900 HT Sequence Detection System. Various collections of samples are assembled on the plates, and referred to as Panel 1 (containing normal tissues and cancer cell lines), Panel 2 (containing samples derived from tissues from normal and cancer sources), Panel 3 (containing cancer cell lines), Panel 4 (containing cells and cell lines from normal tissues and cells related to inflammatory conditions), Panel 5D/5I (containing human tissues and cell lines with an emphasis on metabolic diseases), AI_comprehensive_panel (containing normal tissue and samples from autoimmune/autoinflammatory diseases), Panel CNSD.01 (containing samples from normal and diseased brains) and CNS_neurodegeneration_panel (containing samples from normal and Alzheimer's diseased brains).

[0540] RNA integrity from all samples is controlled for quality by visual assessment of agarose gel electropherograms using 28S and 18S ribosomal RNA staining intensity ratio as a guide (2:1 to 2.5:1 28s:18s) and the absence of low molecular weight RNAs that would be indicative of degradation products. Samples are controlled against genomic DNA contamination by RTQ PCR reactions run in the absence of reverse transcriptase using probe and primer sets designed to amplify across the span of a single exon.

[0541] First, the RNA samples were normalized to reference nucleic acids such as constitutively expressed genes (for example, β-actin and GAPDH). Normalized RNA (5 ul) was converted to cDNA and analyzed by RTQ-PCR using One Step RT-PCR Master Mix Reagents (Applied Biosystems; Catalog No. 4309169) and gene-specific primers according to the manufacturer's instructions.

[0542] In other cases, non-normalized RNA samples were converted to single strand cDNA (sscDNA) using Superscript II (Invitrogen Corporation; Catalog No. 18064-147) and random hexamers according to the manufacturer's instructions. Reactions containing up to 10 μg of total RNA were performed in a volume of 20 μl and incubated for 60 minutes at 42° C. This reaction can be scaled up to 50 μg of total RNA in a final volume of 100 μl. sscDNA samples are then normalized to reference nucleic acids as described previously, using 1×TaqMan® Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer's instructions.

[0543] Probes and primers were designed for each assay according to Applied Biosystems Primer Express Software package (version I for Apple Computer's Macintosh Power PC) or a similar algorithm using the target sequence as input. Default settings were used for reaction conditions and the following parameters were set before selecting primers: primer concentration=250 nM, primer melting temperature (Tm) range =58°-60° C., primer optimal Tm=59° C., maximum primer difference=2° C., probe does not have 5′G, probe Tm must be 10° C. greater than primer Tm, amplicon size 75 bp to 100 bp. The probes and primers selected (see below) were synthesized by Synthegen (Houston, Tex., USA). Probes were double purified by HPLC to remove uncoupled dye and evaluated by mass spectroscopy to verify coupling of reporter and quencher dyes to the 5′ and 3′ ends of the probe, respectively. Their final concentrations were: forward and reverse primers, 900 nM each, and probe, 200 nM.

[0544] PCR conditions: When working with RNA samples, normalized RNA from each tissue and each cell line was spotted in each well of either a 96 well or a 384-well PCR plate (Applied Biosystems). PCR cocktails included either a single gene specific probe and primers set, or two multiplexed probe and primers sets (a set specific for the target clone and another gene-specific set multiplexed with the target probe). PCR reactions were set up using TaqMan® One-Step RT-PCR Master Mix (Applied Biosystems, Catalog No. 4313803) following manufacturer's instructions. Reverse transcription was performed at 48° C. for 30 minutes followed by amplification/PCR cycles as follows: 95° C. 10 min, then 40 cycles of 95° C. for 15 seconds, 60° C. for 1 minute. Results were recorded as CT values (cycle at which a given sample crosses a threshold level of fluorescence) using a log scale, with the difference in RNA concentration between a given sample and the sample with the lowest CT value being represented as 2 to the power of delta CT. The percent relative expression is then obtained by taking the reciprocal of this RNA difference and multiplying by 100.

[0545] When working with sscDNA samples, normalized sscDNA was used as described previously for RNA samples. PCR reactions containing one or two sets of probe and primers were set up as described previously, using 1×TaqMan® Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer's instructions. PCR amplification was performed as follows: 95° C. 10 min, then 40 cycles of 95° C. for 15 seconds, 60° C. for 1 minute. Results were analyzed and processed as described previously.

Panels 1, 1.1, 1.2, and 1.3D

[0546] The plates for Panels 1, 1.1, 1.2 and 1.3D include 2 control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in these panels are broken into 2 classes: samples derived from cultured cell lines and samples derived from primary normal tissues. The cell lines are derived from cancers of the following types: lung cancer, breast cancer, melanoma, colon cancer, prostate cancer, CNS cancer, squamous cell carcinoma, ovarian cancer, liver cancer, renal cancer, gastric cancer and pancreatic cancer. Cell lines used in these panels are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured using the conditions recommended by the ATCC. The normal tissues found on these panels are comprised of samples derived from all major organ systems from single adult individuals or fetuses. These samples are derived from the following organs: adult skeletal muscle, fetal skeletal muscle, adult heart, fetal heart, adult kidney, fetal kidney, adult liver, fetal liver, adult lung, fetal lung, various regions of the brain, the spleen, bone marrow, lymph node, pancreas, salivary gland, pituitary gland, adrenal gland, spinal cord, thymus, stomach, small intestine, colon, bladder, trachea, breast, ovary, uterus, placenta, prostate, testis and adipose.

[0547] In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used:

[0548] ca.=carcinoma,

[0549] *=established from metastasis,

[0550] met=metastasis,

[0551] s cell var=small cell variant,

[0552] non-s=non-sm=non-small,

[0553] squam=squamous,

[0554] pl. eff=pl effusion=pleural effusion,

[0555] glio=glioma,

[0556] astro=astrocytoma, and

[0557] neuro=neuroblastoma.

General_screening_panel_v1.4, v1.5 and v1.6

[0558] The plates for Panels 1.4, v1.5 and v1.6 include two control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in Panels 1.4, v1.5 and v1.6 are broken into 2 classes: samples derived from cultured cell lines and samples derived from primary normal tissues. The cell lines are derived from cancers of the following types: lung cancer, breast cancer, melanoma, colon cancer, prostate cancer, CNS cancer, squamous cell carcinoma, ovarian cancer, liver cancer, renal cancer, gastric cancer and pancreatic cancer. Cell lines used in Panels 1.4, v1.5 and v1.6 are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured using the conditions recommended by the ATCC. The normal tissues found on Panels 1.4, v1.5 and v1.6 are comprised of pools of samples derived from all major organ systems from 2 to 5 different adult individuals or fetuses. These samples are derived from the following organs: adult skeletal muscle, fetal skeletal muscle, adult heart, fetal heart, adult kidney, fetal kidney, adult liver, fetal liver, adult lung, fetal lung, various regions of the brain, the spleen, bone marrow, lymph node, pancreas, salivary gland, pituitary gland, adrenal gland, spinal cord, thymus, stomach, small intestine, colon, bladder, trachea, breast, ovary, uterus, placenta, prostate, testis and adipose. Abbreviations are as described for Panels 1, 1.1, 1.2, and 1.3D.

Panels 2D, 2.2, 2.3 and 2.4

[0559] The plates for Panels 2D, 2.2, 2.3 and 2.4 generally include two control wells and 94 test samples composed of RNA or cDNA isolated from human tissue procured by surgeons working in close cooperation with the National Cancer Institute's Cooperative Human Tissue Network (CHTN) or the National Disease Research Initiative (NDRI) or from Ardais or Clinomics. The tissues are derived from human malignancies and in cases where indicated many malignant tissues have “matched margins” obtained from noncancerous tissue just adjacent to the tumor; These are termed normal adjacent tissues and are denoted “NAT” in the results below. The tumor tissue and the “matched margins” are evaluated by two independent pathologists (the surgical pathologists and again by a pathologist at NDRI/CHTN/Ardais/Clinomics). Unmatched RNA samples from tissues without malignancy (normal tissues) were also obtained from Ardais or Clinomics. This analysis provides a gross histopathological assessment of tumor differentiation grade. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical stage of the patient. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue, in Table RR). In addition, RNA and cDNA samples were obtained from various human tissues derived from autopsies performed on elderly people or sudden death victims (accidents, etc.). These tissues were ascertained to be free of disease and were purchased from various commercial sources such as Clontech (Palo Alto, Calif.), Research Genetics, and Invitrogen. General oncology screening panel_v—2.4 is an updated version of Panel 2D.

HASS Panel v 1.0

[0560] The HASS panel v 1.0 plates are comprised of 93 cDNA samples and two controls. Specifically, 81 of these samples are derived from cultured human cancer cell lines that had been subjected to serum starvation, acidosis and anoxia for different time periods as well as controls for these treatments, 3 samples of human primary cells, 9 samples of malignant brain cancer (4 medulloblastomas and 5 glioblastomas) and 2 controls. The human cancer cell lines are obtained from ATCC (American Type Culture Collection) and fall into the following tissue groups: breast cancer, prostate cancer, bladder carcinomas, pancreatic cancers and CNS cancer cell lines. These cancer cells are all cultured under standard recommended conditions. The treatments used (serum starvation, acidosis and anoxia) have been previously published in the scientific literature. The primary human cells were obtained from Clonetics (Walkersville, Md.) and were grown in the media and conditions recommended by Clonetics. The malignant brain cancer samples are obtained as part of a collaboration (Henry Ford Cancer Center) and are evaluated by a pathologist prior to CuraGen receiving the samples. RNA was prepared from these samples using the standard procedures. The genomic and chemistry control wells have been described previously.

Panels 3D and 3.1

[0561] The plates of Panels 3D and 3.1 are comprised of 94 cDNA samples and two control samples. Specifically, 92 of these samples are derived from cultured human cancer cell lines, 2 samples of human primary cerebellar tissue and 2 controls. The human cell lines are generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: Squamous cell carcinoma of the tongue, breast cancer, prostate cancer, melanoma, epidermoid carcinoma, sarcomas, bladder carcinomas, pancreatic cancers, kidney cancers, leukemias/lymphomas, ovarian/uterine/cervical, gastric, colon, lung and CNS cancer cell lines. In addition, there are two independent samples of cerebellum. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. The cell lines in panel 3D and 1.3D are of the most common cell lines used in the scientific literature. Oncology_cell_line_screening_panel_v3.2 is an updated version of Panel 3. The cell lines in panel 3D, 3.1, 1.3D and oncology_cell_line_screening_panel_v3.2 are of the most common cell lines used in the scientific literature.

Panels 4D, 4R, and 4.1D

[0562] Panel 4 includes samples on a 96 well plate (2 control wells, 94 test samples) composed of RNA (Panel 4R) or cDNA (Panels 4D/4.1D) isolated from various human cell lines or tissues related to inflammatory conditions. Total RNA from control normal tissues such as colon and lung (Stratagene, La Jolla, Calif.) and thymus and kidney (Clontech) was employed. Total RNA from liver tissue from cirrhosis patients and kidney from lupus patients was obtained from BioChain (Biochain Institute, Inc., Hayward, Calif.). Intestinal tissue for RNA preparation from patients diagnosed as having Crohn's disease and ulcerative colitis was obtained from the National Disease Research Interchange (NDRI) (Philadelphia, Pa.).

[0563] Astrocytes, lung fibroblasts, dermal fibroblasts, coronary artery smooth muscle cells, small airway epithelium, bronchial epithelium, microvascular dermal endothelial cells, microvascular lung endothelial cells, human pulmonary aortic endothelial cells, human umbilical vein endothelial cells were all purchased from Clonetics (Walkersville, Md.) and grown in the media supplied for these cell types by Clonetics. These primary cell types were activated with various cytokines or combinations of cytokines for 6 and/or 12-14 hours, as indicated. The following cytokines were used; IL-1 beta at approximately 1-5 ng/ml, TNF alpha at approximately 5-10 ng/ml, IFN gamma at approximately 20-50 ng/ml, IL-4 at approximately 5-10 ng/ml, IL-9 at approximately 5-10 ng/mI, IL-13 at approximately 5-10 ng/ml. Endothelial cells were sometimes starved for various times by culture in the basal media from Clonetics with 0.1% serum.

[0564] Mononuclear cells were prepared from blood of employees at CuraGen Corporation, using Ficoll. LAK cells were prepared from these cells by culture in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco/Life Technologies, Rockville, Md.), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) and Interleukin 2 for 4-6 days. Cells were then either activated with 10-20 ng/ml PMA and 1-2 μg/ml ionomycin, IL-12 at 5-10 ng/ml, IFN gamma at 20-50 ng/ml and IL-18 at 5-10 ng/ml for 6 hours. In some cases, mononuclear cells were cultured for 4-5 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) with PHA (phytohemagglutinin) or PWM (pokeweed mitogen) at approximately 5 μg/ml. Samples were taken at 24, 48 and 72 hours for RNA preparation. MLR (mixed lymphocyte reaction) samples were obtained by taking blood from two donors, isolating the mononuclear cells using Ficoll and mixing the isolated mononuclear cells 1:1 at a final concentration of approximately 2×106 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol (5.5×10−5M) (Gibco), and 10 mM Hepes (Gibco). The MLR was cultured and samples taken at various time points ranging from 1-7 days for RNA preparation.

[0565] Monocytes were isolated from mononuclear cells using CD14 Miltenyi Beads, +ve VS selection columns and a Vario Magnet according to the manufacturer's instructions. Monocytes were differentiated into dendritic cells by culture in DMEM 5% fetal calf serum (FCS) (Hyclone, Logan, Utah), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco), 50 ng/ml GMCSF and 5 ng/ml IL-4 for 5-7 days. Macrophages were prepared by culture of monocytes for 5-7 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco) and 10% AB Human Serum or MCSF at approximately 50 ng/ml. Monocytes, macrophages and dendritic cells were stimulated for 6 and 12-14 hours with lipopolysaccharide (LPS) at 100 ng/ml. Dendritic cells were also stimulated with anti-CD40 monoclonal antibody (Pharmingen) at 10 μg/ml for 6 and 12-14 hours.

[0566] CD4 lymphocytes, CD8 lymphocytes and NK cells were also isolated from mononuclear cells using CD4, CD8 and CD56 Miltenyi beads, positive VS selection columns and a Vario Magnet according to the manufacturer's instructions. CD45RA and CD45RO CD4 lymphocytes were isolated by depleting mononuclear cells of CD8, CD56, CD14 and CD19 cells using CD8, CD56, CD14 and CD19 Miltenyi beads and positive selection. CD45RO beads were then used to isolate the CD45RO CD4 lymphocytes with the remaining cells being CD45RA CD4 lymphocytes. CD45RA CD4, CD45RO CD4 and CD8 lymphocytes were placed in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) and plated at 106 cells/ml onto Falcon 6 well tissue culture plates that had been coated overnight with 0.5 μg/ml anti-CD28 (Pharmingen) and 3 ug/ml anti-CD3 (OKT3, ATCC) in PBS. After 6 and 24 hours, the cells were harvested for RNA preparation. To prepare chronically activated CD8 lymphocytes, we activated the isolated CD8 lymphocytes for 4 days on anti-CD28 and anti-CD3 coated plates and then harvested the cells and expanded them in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) and IL-2. The expanded CDS cells were then activated again with plate bound anti-CD3 and anti-CD28 for 4 days and expanded as before. RNA was isolated 6 and 24 hours after the second activation and after 4 days of the second expansion culture. The isolated NK cells were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) and IL-2 for 4-6 days before RNA was prepared.

[0567] To obtain B cells, tonsils were procured from NDRI. The tonsil was cut up with sterile dissecting scissors and then passed through a sieve. Tonsil cells were then spun down and resupended at 106 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco). To activate the cells, we used PWM at 5 μg/ml or anti-CD40 (Pharmingen) at approximately 10 μg/ml and IL-4 at 5-10 ng/ml. Cells were harvested for RNA preparation at 24, 48 and 72 hours.

[0568] To prepare the primary and secondary Th1/Th2 and Tr1 cells, six-well Falcon plates were coated overnight with 10 μg/ml anti-CD28 (Pharmingen) and 2 μg/ml OKT3 (ATCC), and then washed twice with PBS. Umbilical cord blood CD4 lymphocytes (Poietic Systems, German Town, Md.) were cultured at 105-106 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco) and IL-2 (4 ng/ml). IL-12 (5 ng/ml) and anti-IL4 (1 μg/ml) were used to direct to Th1, while IL-4 (5 ng/ml) and anti-IFN gamma (1 μg/ml) were used to direct to Th2 and IL-10 at 5 ng/ml was used to direct to Tr1. After 4-5 days, the activated Th1, Th2 and Tr1 lymphocytes were washed once in DMEM and expanded for 4-7 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco) and IL-2 (1 ng/ml). Following this, the activated Th1, Th2 and Tr1 lymphocytes were re-stimulated for 5 days with anti-CD28/OKT3 and cytokines as described above, but with the addition of anti-CD95L (1 μg/ml) to prevent apoptosis. After 4-5 days, the Th1, Th2 and Tr1 lymphocytes were washed and then expanded again with IL-2 for 4-7 days. Activated Th1 and Th2 lymphocytes were maintained in this way for a maximum of three cycles. RNA was prepared from primary and secondary Th1, Th2 and Tr1 after 6 and 24 hours following the second and third activations with plate bound anti-CD3 and anti-CD28 mAbs and 4 days into the second and third expansion cultures in Interleukin 2.

[0569] The following leukocyte cells lines were obtained from the ATCC: Ramos, EOL-1, KU-812. EOL cells were further differentiated by culture in 0.1 mM dbcAMP at 5×105 cells/ml for 8 days, changing the media every 3 days and adjusting the cell concentration to 5×105 cells/ml. For the culture of these cells, we used DMEM or RPMI (as recommended by the ATCC), with the addition of 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco). RNA was either prepared from resting cells or cells activated with PMA at 10 ng/ml and ionomycin at 1 μg/ml for 6 and 14 hours. Keratinocyte line CCD106 and an airway epithelial tumor line NCI-H292 were also obtained from the ATCC. Both were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco). CCD1106 cells were activated for 6 and 14 hours with approximately 5 ng/ml TNF alpha and 1 ng/ml IL-1 beta, while NCI-H292 cells were activated for 6 and 14 hours with the following cytokines: 5 ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13 and 25 ng/ml IFN gamma.

[0570] For these cell lines and blood cells, RNA was prepared by lysing approximately 107 cells/ml using Trizol (Gibco BRL). Briefly, {fraction (1/10)} volume of bromochloropropane (Molecular Research Corporation) was added to the RNA sample, vortexed and after 10 minutes at room temperature, the tubes were spun at 14,000 rpm in a Sorvall SS34 rotor. The aqueous phase was removed and placed in a 15 ml Falcon Tube. An equal volume of isopropanol was added and left at −20° C. overnight. The precipitated RNA was spun down at 9,000 rpm for 15 min in a Sorvall SS34 rotor and washed in 70% ethanol. The pellet was redissolved in 300 μl of RNAse-free water and 35 μl buffer (Promega) 5 μl DTT, 7 μl RNAsin and 8 μl DNAse were added. The tube was incubated at 37° C. for 30 minutes to remove contaminating genomic DNA, extracted once with phenol chloroform and re-precipitated with {fraction (1/10)} volume of 3M sodium acetate and 2 volumes of 100% ethanol. The RNA was spun down and placed in RNAse free water. RNA was stored at −80° C.

AI_comprehensive panel_v1.0

[0571] The plates for AI_comprehensive panel_v1.0 include two control wells and 89 test samples comprised of cDNA isolated from surgical and postmortem human tissues obtained from the Backus Hospital and Clinomics (Frederick, Md.). Total RNA was extracted from tissue samples from the Backus Hospital in the Facility at CuraGen. Total RNA from other tissues was obtained from Clinomics.

[0572] Joint tissues including synovial fluid, synovium, bone and cartilage were obtained from patients undergoing total knee or hip replacement surgery at the Backus Hospital. Tissue samples were immediately snap frozen in liquid nitrogen to ensure that isolated RNA was of optimal quality and not degraded. Additional samples of osteoarthritis and rheumatoid arthritis joint tissues were obtained from Clinomics. Normal control tissues were supplied by Clinomics and were obtained during autopsy of trauma victims.

[0573] Surgical specimens of psoriatic tissues and adjacent matched tissues were provided as total RNA by Clinomics. Two male and two female patients were selected between the ages of 25 and 47. None of the patients were taking prescription drugs at the time samples were isolated.

[0574] Surgical specimens of diseased colon from patients with ulcerative colitis and Crohns disease and adjacent matched tissues were obtained from Clinomics. Bowel tissue from three female and three male Crohn's patients between the ages of 41-69 were used. Two patients were not on prescription medication while the others were taking dexamethasone, phenobarbital, or tylenol. Ulcerative colitis tissue was from three male and four female patients. Four of the patients were taking lebvid and two were on phenobarbital.

[0575] Total RNA from post mortem lung tissue from trauma victims with no disease or with emphysema, asthma or COPD was purchased from Clinomics. Emphysema patients ranged in age from 40-70 and all were smokers, this age range was chosen to focus on patients with cigarette-linked emphysema and to avoid those patients with alpha-1anti-trypsin deficiencies. Asthma patients ranged in age from 36-75, and excluded smokers to prevent those patients that could also have COPD. COPD patients ranged in age from 35-80 and included both smokers and non-smokers. Most patients were taking corticosteroids, and bronchodilators.

[0576] In the labels employed to identify tissues in the AI_comprehensive panel_v1.0 panel, the following abbreviations are used:

[0577] AI=Autoimmunity

[0578] Syn=Synovial

[0579] Normal=No apparent disease

[0580] Rep22/Rep20=individual patients

[0581] RA=Rheumatoid arthritis

[0582] Backus=From Backus Hospital

[0583] OA=Osteoarthritis

[0584] (SS) (BA) (MF)=Individual patients

[0585] Adj=Adjacent tissue

[0586] Match control=adjacent tissues

[0587] -M=Male

[0588] -F=Female

[0589] COPD=Chronic obstructive pulmonary disease

Panels 5D and 5I

[0590] The plates for Panel 5D and 5I include two control wells and a variety of cDNAs isolated from human tissues and cell lines with an emphasis on metabolic diseases. Metabolic tissues were obtained from patients enrolled in the Gestational Diabetes study. Cells were obtained during different stages in the differentiation of adipocytes from human mesenchymal stem cells. Human pancreatic islets were also obtained.

[0591] In the Gestational Diabetes study subjects are young (18-40 years), otherwise healthy women with and without gestational diabetes undergoing routine (elective) Caesarean section. After delivery of the infant, when the surgical incisions were being repaired/closed, the obstetrician removed a small sample (<1 cc) of the exposed metabolic tissues during the closure of each surgical level. The biopsy material was rinsed in sterile saline, blotted and fast frozen within 5 minutes from the time of removal. The tissue was then flash frozen in liquid nitrogen and stored, individually, in sterile screw-top tubes and kept on dry ice for shipment to or to be picked up by CuraGen. The metabolic tissues of interest include uterine wall (smooth muscle), visceral adipose, skeletal muscle (rectus) and subcutaneous adipose. Patient descriptions are as follows:

[0592] Patient 2 Diabetic Hispanic, overweight, not on insulin

[0593] Patient 7-9 Nondiabetic Caucasian and obese (BMI>30)

[0594] Patient 10 Diabetic Hispanic, overweight, on insulin

[0595] Patient 11 Nondiabetic African American and overweight

[0596] Patient 12 Diabetic Hispanic on insulin

[0597] Adipocyte differentiation was induced in donor progenitor cells obtained from Osirus (a division of Clonetics/BioWhittaker) in triplicate, except for Donor 3U which had only two replicates. Scientists at Clonetics isolated, grew and differentiated human mesenchymal stem cells (HuMSCs) for CuraGen based on the published protocol found in Mark F. Pittenger, et al., Multilineage Potential of Adult Human Mesenchymal Stem Cells Science Apr. 2, 1999: 143-147. Clonetics provided Trizol lysates or frozen pellets suitable for mRNA isolation and ds cDNA production. A general description of each donor is as follows:

[0598] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose

[0599] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated

[0600] Donor 2 and 3 AD: Adipose, Adipose Differentiated

[0601] Human cell lines were generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: kidney proximal convoluted tubule, uterine smooth muscle cells, small intestine, liver HepG2 cancer cells, heart primary stromal cells, and adrenal cortical adenoma cells. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. All samples were processed at CuraGen to produce single stranded cDNA.

[0602] Panel 5I contains all samples previously described with the addition of pancreatic islets from a 58 year old female patient obtained from the Diabetes Research Institute at the University of Miami School of Medicine. Islet tissue was processed to total RNA at an outside source and delivered to CuraGen for addition to panel 5I.

[0603] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:

[0604] GO Adipose=Greater Omentum Adipose

[0605] SK=Skeletal Muscle

[0606] UT=Uterus

[0607] PL=Placenta

[0608] AD=Adipose Differentiated

[0609] AM=Adipose Midway Differentiated

[0610] U=Undifferentiated Stem Cells

Panel CNSD.01

[0611] The plates for Panel CNSD.01 include two control wells and 94 test samples comprised of cDNA isolated from postmortem human brain tissue obtained from the Harvard Brain Tissue Resource Center. Brains are removed from calvaria of donors between 4 and 24 hours after death, sectioned by neuroanatomists, and frozen at −80° C. in liquid nitrogen vapor. All brains are sectioned and examined by neuropathologists to confirm diagnoses with clear associated neuropathology.

[0612] Disease diagnoses are taken from patient records. The panel contains two brains from each of the following diagnoses: Alzheimer's disease, Parkinson's disease, Huntington's disease, Progressive Supernuclear Palsy, Depression, and “Normal controls”. Within each of these brains, the following regions are represented: cingulate gyrus, temporal pole, globus palladus, substantia nigra, Brodman Area 4 (primary motor strip), Brodman Area 7 (parietal cortex), Brodman Area 9 (prefrontal cortex), and Brodman area 17 (occipital cortex). Not all brain regions are represented in all cases; e.g., Huntington's disease is characterized in part by neurodegeneration in the globus palladus, thus this region is impossible to obtain from confirmed Huntington's cases. Likewise Parkinson's disease is characterized by degeneration of the substantia nigra making this region more difficult to obtain. Normal control brains were examined for neuropathology and found to be free of any pathology consistent with neurodegeneration.

[0613] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:

[0614] PSP=Progressive supranuclear palsy

[0615] Sub Nigra=Substantia nigra

[0616] Glob Palladus=Globus palladus

[0617] Temp Pole=Temporal pole

[0618] Cing Gyr=Cingulate gyrus

[0619] BA 4=Brodman Area 4

Panel CNS_Neurodegeneration_V1.0

[0620] The plates for Panel CNS_Neurodegeneration_V1.0 include two control wells and 47 test samples comprised of cDNA isolated from postmortem human brain tissue obtained from the Harvard Brain Tissue Resource Center (McLean Hospital) and the Human Brain and Spinal Fluid Resource Center (VA Greater Los Angeles Healthcare System). Brains are removed from calvaria of donors between 4 and 24 hours after death, sectioned by neuroanatomists, and frozen at −80° C. in liquid nitrogen vapor. All brains are sectioned and examined by neuropathologists to confirm diagnoses with clear associated neuropathology.

[0621] Disease diagnoses are taken from patient records. The panel contains six brains from Alzheimer's disease (AD) patients, and eight brains from “Normal controls” who showed no evidence of dementia prior to death. The eight normal control brains are divided into two categories: Controls with no dementia and no Alzheimer's like pathology (Controls) and controls with no dementia but evidence of severe Alzheimer's like pathology, (specifically senile plaque load rated as level 3 on a scale of 0-3; 0=no evidence of plaques, 3=severe AD senile plaque load). Within each of these brains, the following regions are represented: hippocampus, temporal cortex (Brodman Area 21), parietal cortex (Brodman area 7), and occipital cortex (Brodman area 17). These regions were chosen to encompass all levels of neurodegeneration in AD. The hippocampus is a region of early and severe neuronal loss in AD; the temporal cortex is known to show neurodegeneration in AD after the hippocampus; the parietal cortex shows moderate neuronal death in the late stages of the disease; the occipital cortex is spared in AD and therefore acts as a “control” region within AD patients. Not all brain regions are represented in all cases.

[0622] In the labels employed to identify tissues in the CNS_Neurodegeneration_V1.0 panel, the following abbreviations are used:

[0623] AD=Alzheimer's disease brain; patient was demented and showed AD-like pathology upon autopsy

[0624] Control=Control brains; patient not demented, showing no neuropathology

[0625] Control (Path)=Control brains; pateint not demented but showing sever AD-like pathology

[0626] SupTemporal Ctx=Superior Temporal Cortex

[0627] Inf Temporal Ctx=Inferior Temporal Cortex

[0628] A. CG100073-01: Taste Receptor T1R1-like

[0629] Expression of gene CG100073-01 was assessed using the primer-probe set Ag4161, described in Table AA. Results of the RTQ-PCR runs are shown in Tables AB, AC, AD and AE.

TABLE AA
Probe Name Ag4161
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-tcatactggccttcctctacaa-3′	22	2202	354
Probe	TET-5′-cctttgcctgcagctacctgggtaag-3′-	26	2244	355
	TAMRA
Reverse	5′-cgttgtagttctctggcaagtc-3′	22	2270	356

[0630]

TABLE AB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	(%)		(%)
	Exp.		Exp.
	Ag4161,		Ag4161,
	Run		Run
Tissue Name	215342812	Tissue Name	215342812
AD 1 Hippo	13.3	Control (Path) 3 Temporal	0.0
		Ctx
AD 2 Hippo	31.4	Control (Path) 4 Temporal	10.8
		Ctx
AD 3 Hippo	5.8	AD 1 Occipital Ctx	17.9
AD 4 Hippo	0.0	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	50.7	AD 3 Occipital Ctx	0.0
AD 6 Hippo	100.0	AD 4 Occipital Ctx	0.6
Control 2	39.5	AD 5 Occipital Ctx	5.6
Hippo
Control 4	0.0	AD 6 Occipital Ctx	27.4
Hippo
Control (Path)	1.3	Control 1	0.0
3 Hippo		Occipital Ctx
AD 1 Temporal	22.5	Control 2	73.7
Ctx		Occipital Ctx
AD 2 Temporal	14.3	Control 3	0.0
Ctx		Occipital Ctx
AD 3 Temporal	0.0	Control 4	0.0
Ctx		Occipital Ctx
AD 4 Temporal	0.8	Control (Path) 1	81.2
Ctx		Occipital Ctx
AD 5 Inf	75.3	Control (Path) 2	1.3
Temporal Ctx		Occipital Ctx
AD 6 Sup	33.9	Control (Path) 3	0.0
Temporal Ctx		Occipital Ctx
AD 6 Inf	43.5	Control (Path) 4	34.6
Temporal Ctx		Occipital Ctx
AD 6 Sup	54.7	Control 1 Parietal Ctx	0.0
Temporal Ctx
Control 1	0.0	Control 2 Parietal Ctx	41.5
Temporal Ctx
Control 2	1.2	Control 3 Parietal Ctx	0.0
Temporal Ctx
Control 3	5.6	Control (Path) 1	30.8
Temporal Ctx		Parietal Ctx
Control 4	0.0	Control (Path) 2	16.4
Temporal Ctx		Parietal Ctx
Control (Path)	15.3	Control (Path)	0.7
1 Temporal Ctx		3 Parietal Ctx
Control (Path)	32.1	Control (Path)	5.1
2 Temporal Ctx		4 Parietal Ctx

[0631]

TABLE AC
General_screening_panel_v1.4
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag4161,		Ag4161,
	Run		Run
Tissue Name	221392098	Tissue Name	221302098
Adipose	18.6	Renal ca. TK-10	11.7
Melanoma*	0.5	Bladder	1.9
Hs688(A).T		Gastric ca.	6.9
Melanoma*	1.4	(liver met.)
Hs688(B).T		NCI-N87
Melanoma* M14	2.4	Gastric ca. KATO III	0.4
Melanoma*	0.4	Colon ca.	0.5
LOXIMVI		SW-948
Melanoma*	0.5	Colon ca.	4.5
SK-MEL-5		SW480
Squamous cell	2.1	Colon ca.*	6.7
carcinoma SCC-4		(SW480 met) SW620
Testis Pool	12.1	Colon ca. HT29	0.9
Prostate ca.*	6.0	Colon ca. HCT-116	1.8
(bone met) PC-3
Prostate Pool	1.0	Colon ca. CaCo-2	2.0
Placenta	0.7	Colon cancer tissue	0.0
Uterus Pool	0.9	Colon ca. SW1116	0.4
Ovarian ca.	6.9	Colon ca. Colo-205	0.0
OVCAR-3
Ovarian ca.	2.4	Colon ca. SW-48	0.0
SK-OV-3
Ovarian ca.	0.5	Colon Pool	2.1
OVCAR-4
Ovarian ca.	15.4	Smnall Intestine Pool	4.9
OVCAR-5
Ovarian ca.	2.1	Stomach Pool	2.7
IGROV-1
Ovarian ca.	4.1	Bone Marrow Pool	3.3
OVCAR-8
Ovary	3.7	Fetal Heart	1.0
Breast ca. MCF-7	0.0	Heart Pool	2.4
Breast ca.	0.5	Lymph Node Pool	4.4
MDA-MB-231
Breast ca. BT 549	6.0	Fetal Skeletal Muscle	6.6
Breast ca. T47D	33.9	Skeletal Muscle Pool	8.3
Breast ca. MDA-N	2.2	Spleen Pool	1.1
Breast Pool	1.3	Thymus Pool	2.4
Trachea	4.7	CNS cancer	4.7
		(glio/astro) U87-MG
Lung	5.9	CNS cancer	10.2
		(glio/astro)
		U-118-MG
Fetal Lung	3.5	CNS cancer	2.4
		(neuro; met) SK-N-AS
Lung ca. NCI-N417	1.3	CNS cancer (astro)	2.3
		SF-539
Lung ca. LX-1	2.3	CNS cancer (astro)	9.2
		SNB-75
Lung ca. NCI-H146	0.9	CNS cancer (glio)	1.5
		SNB-19
Lung ca. SHP-77	100.0	CNS cancer (glio)	11.2
		SF-295
Lung ca. A549	2.7	Brain (Amygdala)	2.6
		Pool
Lung ca. NCI-H526	36.6	Brain (cerebellum)	10.2
Lung ca. NCI-H23	39.2	Brain (fetal)	4.0
Lung ca. NCI-H460	1.4	Brain (Hippocampus)	0.5
		Pool
Lung ca. HOP-62	8.2	Cerebral Cortex Pool	2.2
Lung ca. NCI-H522	12.7	Brain	1.9
		(Substantia nigra)
		Pool
Liver	0.0	Brain (Thalamus) Pool	2.7
Fetal Liver	0.5	Brain (whole)	2.6
Liver ca. HepG2	24.1	Spinal Cord Pool	2.2
Kidney Pool	20.7	Adrenal Gland	3.6
Fetal Kidney	0.9	Pituitary gland Pool	3.3
Renal ca. 786-0	2.4	Salivary Gland	1.2
Renal ca. A498	0.5	Thyroid (female)	4.0
Renal ca. ACHN	1.9	Pancreatic ca.	3.0
		CAPAN2
Renal ca. UO-31	0.6	Pancreas Pool	4.8

[0632]

TABLE AD
Panel 4.1D
	Rel.		Rel.
	Exp.		Exp.
	(%)		(%)
	Ag4161,		Ag4161,
	Run		Run
Tissue Name	173333747	Tissue Name	173333747
Secondary Th1 act	0.0	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha +	0.0
		IFN gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha +	0.0
		IL4
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	0.2	Lung Microvascular	0.0
		EC none
Primary Th1 act	1.1	Lung	0.0
		Microvascular EC
		TNFalpha + IL-1beta
Primary Th2 act	0.2	Microvascular	0.0
		Dermal EC none
Primary Tr1 act	0.0	Microsvasular	0.0
		Dermal EC
		TNFalpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	0.0
		TNFalpha + IL1beta
Primary Th2 rest	0.0	Small airway	0.0
		epithelium none
Primary Tr1 rest	1.8	Small airway	0.0
		epithelium
		TNFalpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC	0.0
lymphocyte act		rest
CD45RO CD4	0.0	Coronery artery SMC	0.0
lymphocyte act		TNFalpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes +	0.0
lymphocyte rest		TNFalpha IL-1beta
Secondary CD8	0.0	KU-812 (Basophil)	0.0
lymphocyte act		rest
CD4 lymphocyte	1.0	KU-812 (Basophil)	0.0
none		PMA/ionomycin
2ry Th1/Th2/	0.0	CCD1106	0.0
Tr1_anti-CD95		(Kerainocytes) none
CH11
LAK cells rest	0.2	CCD1106	0.0
		(Keratinocytes) none
		TNFalpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.0
LAk cells IL-2 +	0.0	NCI-H292 none	0.0
IL-12
LAK cells IL-2 +	0.0	NCI-H292 IL-4	0.0
IFN gamma
LAK cells IL-2 +	0.0	NCI-H292 IL-9	0.2
IL-18
LAK cells	0.0	NCI-H292 IL-13	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR	0.0	HPAEC none	0.0
3 day
Two Way MLR	0.0	HPAEC TNF alpha +	0.0
5 day		IL-1beta
Two Way MLR	0.0	Lung fibroblast none	0.0
7 day
PBMC rest	0.0	Lung fibroblast	0.0
		TNF alpha +
		IL-1beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.0
Ramos (B cell)	0.6	Lung fibroblast	0.0
ionomycin		IFN gamma
B lymphocytes	0.0	Dermal fibroblast	0.3
PWM		CCD1070 rest
B lymphocytes	1.0	Dermal fibroblast	0.0
CD40L and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast	0.0
		CCD1070 IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast	2.8
PMA/ionomycin		IFN gamma
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.9
Dendritic cells LPS	0.0	Dermal Fibroblasts	0.7
		rest
Dendritic cells	0.0	Neutrophils TNFa +	6.5
anti-CD40		LPS
Monocytes rest	4.8	Neutrophils rest	3.4
Monocytes LPS	0.2	Colon	1.7
Macrophages rest	0.0	Lung	1.1
Macrophages LPS	0.0	Thymus	9.8
HUVEC none	0.0	Kidney	190.0
HUVEC starved	0.0

[0633]

TABLE AE
general oncology screening panel_v_2.4
	Rel.		Rel.
	Exp.		Exp.
	(%)		(%)
	Ag4161,		Ag4161,
	Run		Run
Tissue Name	268624164	Tissue Name	268624164
Colon cancer 1	0.0	Bladder NAT 2	0.0
Colon NAT 1	5.4	Bladder NAT 3	0.0
Colon cancer 2	0.0	Bladder NAT 4	0.0
Colon NAT 2	3.4	Prostate adenocarcinoma 1	0.0
Colon cancer 3	11.7	Prostate adenocarcinoma 2	0.0
Colon NAT 3	12.1	Prostate adenocarcinoma 3	2.2
Colon	8.5	Prostate adenocarcinoma 4	0.0
malignant
cancer
Colon NAT 4	8.6	Prostate NAT 5	2.8
Lung cancer 1	1.4	Prostate adenocarcinoma 6	0.0
Lung NAT 1	3.2	Prostate adenocarcinoma 7	0.0
Lung cancer 2	27.4	Prostate adenocarcinoma 8	0.5
Lung NAT 2	9.7	Prostate adenocarcinoma 9	4.0
Squamous cell	17.7	Prostate NAT 10	0.0
carcinoma 3
Lung NAT 3	0.0	Kidney cancer 1	16.8
Metastatic	17.7	Kidney NAT 1	0.0
melanoma 1
Melanoma 2	9.8	Kidney cancer 2	49.3
Melanoma 3	32.3	Kidney NAT 2	23.3
Metastatic	100.0	Kidney cancer 3	7.6
melanoma 4
Metastatic	42.9	Kidney NAT 3	9.7
melanoma 5
Bladder	0.0	Kidney cancer 4	0.0
cancer 1
Bladder NAT 1	0.0	Kidney NAT 4	11.1
Bladder	4.2
cancer 2

[0634] CNS_neurodegeneration_v1.0 Summary: Ag4161 This gene represents a novel G-protein coupled receptor (GPCR) with expression in the brain. The GPCR family of receptors contains a large number of neurotransmitter receptors, including the dopamine, serotonin, a and b-adrenergic, acetylcholine muscarinic, histamine, peptide, and metabotropic glutamate receptors. GPCRs are excellent drug targets in various neurologic and psychiatric diseases. All antipsychotics have been shown to act at the dopamine D2 receptor; similarly novel antipsychotics also act at the serotonergic receptor, and often the muscarinic and adrenergic receptors as well. While the majority of antidepressants can be classified as selective serotonin reuptake inhibitors, blockade of the 5-HT1A and a2 adrenergic receptors increases the effects of these drugs. The GPCRs are also of use as drug targets in the treatment of stroke. Blockade of the glutamate receptors may decrease the neuronal death resulting from excitotoxicity; further more the purinergic receptors have also been implicated as drug targets in the treatment of cerebral ischemia. The b-adrenergic receptors have been implicated in the treatment of ADHD with Ritalin, while the a-adrenergic receptors have been implicated in memory. Therefore this gene may be of use as a small molecule target for the treatment of any of the described diseases.

[0635] In addition, this GPCR appears to be slightly upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, blockade of this receptor may decrease neuronal death and be of use in the treatment of this disease.

[0636] References:

[0637] El Yacoubi M, Ledent C, Parmentier M, Bertorelli R, Ongini E, Costentin J, Vaugeois J M. Adenosine A2A receptor antagonists are potential antidepressants: evidence based on pharmacology and A2A receptor knockout mice. Br J Pharmacol September 2001;134(1):68-77.

[0638] Blier P. Pharmacology of rapid-onset antidepressant treatment strategies. Clin Psychiatry 2001;62 Suppl 15:12-7.

[0639] Tranquillini M E, Reggiani A. Glycine-site antagonists and stroke. Expert Opin Investig Drugs November 1999; 8(11):1837-1848.

[0640] Monopoli A, Lozza G, Forlani A, Mattavelli A, Ongini E. Blockade of adenosine A2A receptors by SCH 58261 results in neuroprotective effects in cerebral ischaemia in rats. Neuroreport Dec. 1, 1998;9(17):3955-9.

[0641] General_screening_panel_v1.4 Summary: Ag4161 Highest expression of this gene is seen in a lung cancer cell line (CT=29.7). In addition, this gene is expressed widely throughout this pane, with low but significant levels of expression cell lines derived from brain, renal, colon, gastric, breast, ovarian, and prostate cancers. Thus, expression of this gene could be used to differentiate this lung cancer cell line sample from other samples on this panel and as a marker of lung cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of lung cancer.

[0642] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0643] Panel 4.1D Summary: Ag4161 Expression of this gene is limited to kidney, thymus and neutrophils in this panel, with highest expression in the kidney (CT=29.3). Thus, expression of this gene could be used to differentiate between the kidney derived sample and other samples on this panel and as a marker of kidney tissue. The putative GPCR encoded for by this gene may allow cells within the kidney to respond to specific microenvironmental signals (For example, ref. 1). Therefore, antibody or small molecule therapies designed with the protein encoded for by this gene could modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.

[0644] References:

[0645] 1. Mark M. D., Wittemann S., Herlitze S. (2000) G protein modulation of recombinant P/Q-type calcium channels by regulators of G protein signalling proteins. J. Physiol. 528 Pt 1: 65-77.

[0646] general oncology screening panel_v—2.4 Summary: Ag4161 Highest expression of this gene is seen in a melanoma sample (CT=32.1). In addition, expression is seen in a cluster of samples derived from melanoma. Thus, modulation of this gene product may be useful in the treatment of this cancer.

[0647] B. CG103679-02, CG103679-03, CG103679-06, and CG103679-07: Asparaginase

[0648] Expression of gene CG103679-02, CG103679-03, CG103679-06, and CG103679-07 was assessed using the primer-probe sets Ag4552, Ag4712, Ag4940, Ag5249 and Ag5250, described in Tables BA, BB, BC, BD and BE. Results of the RTQ-PCR runs are shown in Tables BF, BG, BH, BI, BJ, BK, BL and BM. Please note that CG103679-06 represents a full-length physical clone of the CG103679-02 gene, validating the prediction of the gene sequence. Please not that primer-probe sets Ag4712, and Ag5249 is specific for the CG103679-03 variant.

TABLE BA
Probe Name Ag4552
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gaaagcatcctgaaggtgaac-3′	21	1021	357
Probe	TET-5′-ctggctagactcaccctgttccacat-3′-TAMRA	26	1042	358
Reverse	5′-cagcctcttctaccgtcttacc-3′	22	1075	359

[0649]

TABLE BB
Probe Name Ag4712
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gcagcttgtagaagcaagaaaa-3′	22	33	157
Probe	TET-5′-ctcttctggagcttcccgaaggaact-3′-TAMRA	26	63	158
Reverse	5′-gttctggtggtcagaaattcaa-3′	22	107	159

[0650]

TABLE BC
Probe Name Ag4940
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tggactgcaaagggaatgta-3′	20	875	160
Probe	TET-5′-caacctccacaggcggtatcgttaat-3′-TAMRA	26	902	161
Reverse	5′-cagctcctagacacggtgagt-3′	21	950	162

[0651]

TABLE BD
Probe Name Ag5249
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ttctggagcttcccgaag-3′	18	66	163
Probe	TET-5′-ccctgcagacccagtttgaatttctg-3′-TAMRA	26	92	164
Reverse	5′-ctcagcccgccacc-3′	14	154	165

[0652]

TABLE BE
Probe Name Ag5250
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-atggaaaagacctgtctgca-3′	20	602	166
Probe	TET-5′-agcagtgtccgcagtccagtgtatagc-3′-TAMRA	27	624	167
Reverse	5′-tccatgacaagccgagc-3′	17	667	168

[0653]

TABLE BF
AI_comprehensive panel_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4940,		Ag4940,
	Run		Run
Tissue Name	218648855	Tissue Name	218648855
110967 COPD-F	1.2	112427 Match Control Psoriasis-F	17.4
110980 COPD-F	0.5	112418 Psoriasis-M	2.1
110968 COPD-M	0.7	112723 Match Control Psoriasis-M	0.3
110977 COPD-M	6.7	112419 Psoriasis-M	1.8
110989 Emphysema-F	18.3	112424 Match Control Psoriasis-M	1.2
110992 Emphysema-F	23.0	112420 Psoriasis-M	59.5
110993 Emphysema-F	2.0	112425 Match Control Psoriasis-M	23.3
110994 Emphysema-F	0.6	104689 (MF) OA Bone-Backus	3.3
110995 Emphysema-F	69.7	104690 (MF) Adj “Normal” Bone-	1.7
		Backus
110996 Emphysema-F	10.5	104691 (MF) OA Synovium-	2.9
		Backus
110997 Asthma-M	3.7	104692 (BA) OA Cartilage-Backus	0.4
111001 Asthma-F	12.5	104694 (BA) OA Bone-Backus	2.2
111002 Asthma-F	29.9	104695 (BA) Adj “Normal” Bone-	2.5
		Backus
111003 Atopic Asthma-F	31.2	104696 (BA) OA Synovium-	2.4
		Backus
111004 Atopic Asthma-F	100.0	104700 (SS) OA Bone-Backus	3.3
111005 Atopic Asthma-F	50.7	104701 (SS) Adj “Normal” Bone
		Backus
111006 Atopic Asthma-F	6.5	104702 (SS) OA Synovium-Backus	6.0
111417 Allergy-M	27.0	117093 OA Cartilage Rep7	24.5
112347 Allergy-M	0.3	112672 OA Bone5	4.3
112349 Normal Lung-F	0.2	112673 OA Synovium5	2.4
112357 Normal Lung-F	1.2	112674 OA Synovial Fluid cells5	1.7
112354 Normal Lung-M	0.7	117100 OA Cartilage Rep14	2.9
112374 Crohns-F	1.7	112756 OA Bone9	52.1
112389 Match Control Crohns-F	0.7	112757 OA Synovium9	1.7
112375 Crohns-F	1.3	112758 OA Synovial Fluid Cells9	2.0
112732 Match Control Crohns-F	1.0	117125 RA Cartilage Rep2	1.8
112725 Crohns-M	0.5	113492 Bone2 RA	10.1
112387 Match Control Crohns-M	7.5	113493 Synovium2 RA	4.7
112378 Crohns-M	0.3	113494 Syn Fluid Cells RA	7.3
112390 Match Control Crohns-M	17.1	113499 Cartilage4 RA	10.6
112726 Crohns-M	23.3	113500 Bone4 RA	11.1
112731 Match Control Crohns-M	20.7	113501 Synovium4 RA	11.3
112380 Ulcer Col-F	17.8	113502 Syn Fluid Cells4 RA	5.6
112734 Match Control Ulcer Col-	2.3	113495 Cartilage3 RA	7.4
F
112384 Ulcer Col-F	40.3	113496 Bone3 RA	6.5
112737 Match Control Ulcer Col-	19.9	113497 Synovium3 RA	4.9
F
112386 Ulcer Col-F	0.4	113498 Syn Fluid Cells3 RA	8.4
112738 Match Control Ulcer Col-	11.3	117106 Normal Cartilage Rep20	0.8
F
112381 Ulcer Col-M	0.6	113663 Bone3 Normal	0.2
112735 Match Control Ulcer Col-	1.7	113664 Synovium3 Normal	0.0
M
112382 Ulcer Col-M	0.8	113665 Syn Fluid Cells3 Normal	0.2
112394 Match Control Ulcer Col-	1.0	117107 Normal Cartilage Rep22	0.6
M
112383 Ulcer Col-M	35.1	113667 Bone4 Normal	4.6
112736 Match Control Ulcer Col-	0.5	113668 Synovium4 Normal	8.6
M
112423 Psoriasis-F	1.8	113669 Syn Fluid Cells4 Normal	8.1

[0654]

TABLE BG
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5250,		Ag5250,
	Run		Run
Tissue Name	229929878	Tissue Name	229929878
AD 1 Hippo	15.6	Control (Path) 3 Temporal Ctx	19.5
AD 2 Hippo	38.2	Control (Path) 4 Temporal Ctx	32.8
AD 3 Hippo	8.0	AD 1 Occipital Ctx	18.6
AD 4 Hippo	12.9	AD 2 Occipital Ctx (Missing)	0.0
AD 5 Hippo	100.0	AD 3 Occipital Ctx	14.1
AD 6 Hippo	80.1	AD 4 Occipital Ctx	20.4
Control 2 Hippo	27.9	AD 5 Occipital Ctx	37.4
Control 4 Hippo	16.6	AD 6 Occipital Ctx	50.7
Control (Path) 3 Hippo	10.9	Control 1 Occipital Ctx	11.8
AD 1 Temporal Ctx	17.2	Control 2 Occipital Ctx	50.3
AD 2 Temporal Ctx	35.6	Control 3 Occipital Ctx	33.9
AD 3 Temporal Ctx	8.8	Control 4 Occipital Ctx	13.8
AD 4 Temporal Ctx	31.4	Control (Path) 1 Occipital Ctx	74.7
AD 5 Inf Temporal Ctx	77.9	Control (Path) 2 Occipital Ctx	14.2
AD 5 Sup Temporal Ctx	46.3	Control (Path) 3 Occipital Ctx	13.8
AD 6 Inf Temporal Ctx	80.1	Control (Path) 4 Occipital Ctx	18.6
AD 6 Sup Temporal Ctx	85.9	Control 1 Parietal Ctx	10.0
Control 1 Temporal Ctx	19.8	Control 2 Parietal Ctx	54.0
Control 2 Temporal Ctx	39.8	Control 3 Parietal Ctx	35.6
Control 3 Temporal Ctx	31.0	Control (Path) 1 Parietal Ctx	75.8
Control 3 Temporal Ctx	17.8	Control (Path) 2 Parietal Ctx	30.6
Control (Path) 1 Temporal Ctx	66.0	Control (Path) 3 Parietal Ctx	16.3
Control (Path) 2 Temporal Ctx	43.5	Control (Path) 4 Parietal Ctx	39.0

[0655]

TABLE BH
General_screening_panel_v1.4
	Rel.	Rel.	Rel.
	Exp. (%)	Exp. (%)	Exp. (%)
	Ag4712,	Ag4940,	Ag4940,
	Run	Run	Run
Tissue Name	222825909	219288958	219514734
Adipose	0.0	1.2	1.0
Melanoma*	0.0	0.0	0.0
Hs688(A).T
Melanoma*	0.0	0.1	0.1
Hs688(B).T
Melanoma*	0.0	2.9	3.5
M14
Melanoma*	0.0	0.7	1.5
LOXIMVI
Melanoma*	4.1	4.9	4.7
SK-MEL-5
Squamous cell	0.0	0.1	0.0
carcinoma
SCC-4
Testis Pool	4.7	41.5	49.0
Prostate ca.*	8.8	5.0	6.6
(bone met) PC-
3
Prostate Pool	10.0	3.3	4.7
Placenta	0.0	0.4	0.5
Uterus Pool	0.0	0.6	1.2
Ovarian ca.	0.0	15.8	18.8
OVCAR-3
Ovarian ca. SK-	58.6	100.0	100.0
OV-3
Ovarian ca.	3.5	6.5	9.2
OVCAR-4
Ovarian ca.	18.4	12.9	14.2
OVCAR-5
Ovarian ca.	15.5	39.2	44.4
IGROV-1
Ovarian ca.	17.2	6.2	8.2
OVCAR-8
Ovary	0.0	1.4	1.7
Breast ca.	0.0	2.0	2.5
MCF-7
Breast ca.	0.0	0.4	0.5
MDA-MB-231
Breast ca. BT	0.0	1.4	1.7
549
Breast ca.	17.4	20.7	21.0
T47D
Breast ca.	0.0	1.0	1.0
MDA-N
Breast Pool	100.0	13.1	18.3
Trachea	4.1	6.0	7.1
Lung	4.3	0.1	0.2
Fetal Lung	0.0	4.6	6.2
Lung ca. NCI-	5.4	3.3	3.9
N417
Lung ca. LX-1	7.9	4.5	5.9
Lung ca. NCI-	17.7	21.5	24.3
H146
Lung ca. SHP-77	25.5	32.5	41.2
Lung ca. A549	3.8	10.1	12.8
Lung ca. NCI-	0.0	19.3	23.5
H526
Lung ca. NCI-	20.4	12.0	15.7
H23
Lung ca. NCI-	5.1	0.7	1.2
H460
Lung ca. HOP-	0.0	0.7	0.7
62
Lung ca. NCI-	43.8	83.5	57.8
H522
Liver	0.0	0.0	0.1
Fetal Liver	10.1	1.8	2.2
Liver ca.	0.0	15.8	19.2
HepG2
Kidney Pool	6.7	1.6	1.7
Fetal Kidney	18.0	6.1	6.2
Renal ca. 786-0	0.0	0.7	0.6
Renal ca. A498	0.0	0.5	0.4
Renal ca.	0.0	1.6	2.2
ACHN
Renal ca. UO-	17.0	6.3	8.9
31
Renal ca. TK-10	12.2	12.5	14.0
Bladder	17.9	6.6	9.3
Gastric ca.	0.0	1.9	2.8
(liver met.)
NCI-N87
Gastric ca.	33.7	47.6	56.6
KATO III
Colon ca. SW-948	0.0	4.1	6.1
Colon ca. SW480	19.9	16.6	20.9
Colon ca.*	4.6	7.3	11.2
(SW480 met)
SW620
Colon ca. HT29	6.7	6.0	9.4
Colon ca. HCT-	9.2	27.5	28.3
116
Colon ca. CaCo-2	88.3	27.2	28.9
Colon cancer	4.0	1.7	2.7
tissue
Colon ca. SW1116	8.4	4.4	5.1
Colon ca.	0.0	3.1	3.4
Colo-205
Colon ca. SW-48	3.7	6.3	7.6
Colon Pool	14.4	4.5	6.5
Small Intestine	14.2	3.3	4.7
Pool
Stomach Pool	11.1	11.6	16.2
Bone Marrow Pool	5.4	1.9	1.9
Fetal Heart	0.0	0.7	1.1
Heart Pool	0.0	0.4	0.5
Lymph Node Pool	29.7	11.0	13.1
Fetal Skeletal	0.0	0.4	0.8
Muscle
Skeletal Muscle	0.0	1.1	1.5
Pool
Spleen Pool	4.6	1.2	1.6
Thymus Pool	49.0	19.9	25.2
CNS cancer	4.2	0.1	0.0
(glio/astro)
U87-MG
CNS cancer	0.0	0.3	0.1
(glio/astro)
U-118-MG
CNS cancer	4.6	3.4	3.6
(neuro; met)
SK-N-AS
CNS cancer	0.0	0.1	0.1
(astro)
SF-539
CNS cancer	4.7	3.8	5.1
(astro)
SNB-75
CNS cancer (glio)	35.8	40.1	43.2
SNB-19
CNS cancer (glio)	4.3	1.5	1.3
SF-295
Brain (Amygdala)	7.4	17.2	21.9
Pool
Brain	47.3	31.9	32.8
(cerebellum)
Brain (fetal)	36.6	22.2	28.1
Brain	15.3	26.2	25.9
(Hippocampus)
Pool
Cerebral Cortex	10.7	27.5	33.0
Pool
Brain (Substantia	7.4	24.8	25.3
nigra) Pool
Brain (Thalamus)	7.8	37.6	39.8
Pool
Brain (whole)	18.7	29.7	29.3
Spinal Cord Pool	10.7	13.6	18.3
Adrenal Gland	0.0	1.4	1.0
Pituitary gland	7.7	2.4	3.0
Pool
Salivary Gland	0.0	2.5	2.7
Thyroid (female)	0.0	1.5	1.2
Pancreatic ca.	4.8	3.0	2.9
CAPAN2
Pancreas Pool	41.5	22.1	26.6

[0656]

TABLE BI
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5250,		Ag5250,
	Run		Run
Tissue Name	229827566	Tissue Name	229827566
Adipose	2.2	Renal ca. TK-10	11.9
Melanoma* Hs688(A).T	0.1	Bladder	7.3
Melanoma* Hs688(B).T	0.1	Gastric ca. (liver met.) NCI-N87	3.0
Melanoma* M14	7.0	Gastric ca. KATO III	39.5
Melanoma* LOXIMVI	3.2	Colon ca. SW-948	4.6
Melanoma* SK-MEL-5	7.6	Colon ca. SW480	23.7
Squamous cell carcinoma SCC-4	0.3	Colon ca.* (SW480 met) SW620	9.2
Testis Pool	47.0	Colon ca. HT29	8.2
Prostate ca.* (bone met) PC-3	6.2	Colon ca. HCT-116	29.1
Prostate Pool	6.2	Colon ca. CaCo-2	32.8
Placenta	0.3	Colon cancer tissue	3.6
Uterus Pool	1.0	Colon ca. SW116	3.2
Ovarian ca. OVCAR-3	22.1	Colon ca. Colo-205	3.5
Ovarian ca. SK-OV-3	100.0	Colon ca. SW-48	9.3
Ovarian ca. OVCAR-4	5.4	Colon Pool	6.4
Ovarian ca. OVCAR-5	12.9	Small Intestine Pool	2.9
Ovarian ca. IGROV-1	41.2	Stomach Pool	10.8
Ovarian ca. OVCAR-8	5.2	Bone Marrow Pool	1.3
Ovary	1.0	Fetal Heart	0.7
Breast ca. MCF-7	2.7	Heart Pool	0.5
Breast ca. MDA-MB-231	0.6	Lymph Node Pool	10.5
Breast ca. BT 549	1.3	Fetal Skeletal Muscle	0.5
Breast ca. T47D	1.0	Skeletal Muscle Pool	1.3
Breast ca. MDA-N	2.9	Spleen Pool	1.7
Breast Pool	14.5	Thymus Pool	20.9
Trachea	5.1	CNS cancer (glio/astro) U87-MG	0.2
Lung	0.1	CNS cancer (glio/astro) U-118-MG	0.3
Fetal Lung	5.8	CNS cancer (neuro;met) SK-N-AS	6.6
Lung ca. NCI-N417	6.9	CNS cancer (astro) SF-539	0.4
Lung ca. LX-1	6.5	CNS cancer (astro) SNB-75	5.0
Lung ca. NCI-H146	18.7	CNS cancer (glio) SNB-19	43.8
Lung ca. SHP-77	19.6	CNS cancer (glio) SF-295	1.6
Lung ca. A549	8.7	Brain (Amygdala) Pool	20.3
Lung ca. NCI-H526	18.9	Brain (cerebellum)	56.3
Lung ca. NCI-H23	14.1	Brain (fetal)	13.5
Lung ca. NCI-H460	1.2	Brain (Hippocampus) Pool	20.7
Lung ca. HOP-62	1.0	Cerebral Cortex Pool	24.3
Lung ca. NCI-H522	54.3	Brain (Substantia nigra) Pool	15.7
Liver	0.1	Brain (Thalamus) Pool	32.8
Fetal Liver	1.9	Brain (whole)	24.7
Liver ca. HepG2	16.7	Spinal Cord Pool	11.8
Kidney Pool	1.6	Adrenal Gland	0.7
Fetal Kidney	5.6	Pituitary gland Pool	2.7
Renal ca. 786-0	1.2	Salivary Gland	2.8
Renal ca. A498	0.6	Thyroid (female)	1.4
Renal ca. ACHN	1.9	Pancreatic ca. CAPAN2	5.0
Renal ca. UO-31	6.3	Pancreas Pool	14.3

[0657]

TABLE BJ
Oncology_cell_line_screening_panel_v3.1
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4940,		Ag4940,
	Run		Run
Tissue Name	220982873	Tissue Name	220982873
Daoy Medulloblastoma/Cerebellum	3.5	Ca Ski_Cervical epidermoid	0.0
		carcinoma (metastasis)
TE671 Medulloblastom/Cerebellum	2.0	ES-2_Ovarian clear cell carcinoma	0.2
D283 Med	20.0	Ramos/6h stim_Stimulated with	0.0
Medulloblastoma/Cerebellum		PMA/ionomycin 6h
PFSK-1 Primitive	0.8	Ramos/14h stim_Stimulated with	0.0
Neuroectodermal/Cerebellum		PMA/ionomycin 14h
XF-498_CNS	1.3	MEG-01_Chronic myelogenous	3.5
		leukemia (megokaryoblast)
SNB-78_CNS/glioma	1.0	Raji_Burkitt's lymphoma	0.0
SF-268_CNS/glioblastoma	5.3	Daudi_Burkitt's lymphoma	0.0
T98G_Glioblastoma	1.1	U266_B-cell	6.2
		plasmacytoma/myeloma
SK-N-SH_Neuroblastoma	1.3	CA46_Burkitt's lymphoma	1.0
(metastasis)
SF-295_CNS/glioblastoma	0.5	RL_non-Hodgkin's B-cell	0.7
		lymphoma
Cerebellum	26.4	JM1_pre-B-cell	0.0
		lymphoma/leukemia
Cerebellum	14.1	Jurkat_T cell leukemia	7.1
NCI-H292_Mucoepidermoid lung	2.1	TF-1_Erythroleukemia	2.1
ca.
DMS-114_Small cell lung cancer	5.3	HUT 78_T-cell lymphoma	5.7
DMS-79_Small cell lung	47.6	U937_Histiocytic lymphoma	7.5
cancer/neuroendocrine
NCI-H146_Small cell lung	31.0	KU-812_Myelogenous leukemia	5.7
cancer/neuroendocrine
NCI-H526_Small cell lung	100.0	769-P_Clear cell renal ca.	0.1
cancer/neuroendocrine
NCI-N417_Small cell lung	6.0	Caki-2_Clear cell renal ca.	1.4
cancer/neuroendocrine
NCI-H82_Small cell lung	18.2	SW 839_Clear cell renal ca.	7.9
cancer/neuroendocrine
NCI-H157_Squamous cell lung	0.6	G401_Wilms' tumor	1.4
cancer (metastasis)
NCI-H1155_Large cell lung	37.9	Hs766T_Pancreatic ca. (LN	0.1
cancer/neuroendocrine
NCI-H1299_Large cell lung	7.2	CAPAN-1_Pancreatic	1.4
cancer/neuroendocrine		adenocarcinoma (liver metastasis)
NCI-H727_Lung carcinoid	31.4	SU86.86_Pancreatic carcinoma	3.6
		(liver metastasis)
NCI-UMC-11_Lung carcinoid	58.2	BxPC-3_Pancreatic adenocarcinoma	0.1
LX-1_Small cell lung cancer	4.0	HPAC_Pancreatic adenocarcinoma	0.8
Colo-205_Colon cancer	3.1	MIA PaCa-2_Pancreatic ca.	2.4
KM12_Colon cancer	3.3	CFPAC-1_Pancreatic ductal	7.5
		adenocarcinoma
KM20L2_Colon cancer	0.6	PANC-1_Pancreatic epithelioid	8.5
		ductal ca.
NCI-H716_Colon cancer	27.7	T24_Bladder ca. (transitional cell)	0.5
SW-48_Colon adenocarcinoma	9.9	5637_Bladder ca.	0.8
SW1116_Colon adenocarcinoma	2.9	HT-1197_Bladder ca.	0.0
LS 174T_Colon adenocarcinoma	0.1	UM-UC-3_Bladder ca. (transitional	2.0
		cell)
SW-948_Colon adenocarcinoma	2.7	A204_Rhabdomyosarcoma	0.3
SW-480_Colon adenocarcinoma	2.6	HT-1080_Fibrosarcoma	0.0
NCI-SNU-5_Gastric ca.	4.8	MG-63_Osteosarcoma (bone)	0.2
KATO III_Stomach	11.7	SK-LMS-1_Leiomyosarcoma	1.9
		(vulva)
NCI-SNU-16_Gastric ca.	0.0	SJRH30_Rhabdomyosarcoma (met	2.1
		to bone marrow)
NCI-SNU-1_Gastric ca.	39.2	A431_Epidermoid ca.	2.1
RF-1_Gastric adenocarcinoma	6.4	WM266-4_Melanoma	1.6
RF-48_Gastric adenocarcinoma	6.1	DU 145_Prostate	5.0
MKN-45_Gastric ca.	2.2	MDA-MB-468_Breast	6.4
		adenocarcinoma
NCI-N87_Gastric ca.	0.8	SSC-4_Tongue	0.0
OVCAR-5_Ovarian ca.	1.5	SSC-9_Tongue	0.0
RL95-2_Uterine carcinoma	0.7	SSC-15_Tongue	0.6
HelaS3_Cervical adenocarcinoma	5.7	CAL 27_Squamous cell ca. of	0.0
		tongue

[0658]

TABLE BK
Panel 4.1D
	Rel.	Rel.	Rel.	Rel.	Rel.
	Exp. (%)	Exp. (%)	Exp. (%)	Exp. (%)	Exp. (%)
	Ag4712,	Ag4940,	Ag4940,	Ag4940,	Ag5250,
	Run	Run	Run	Run	Run
Tissue Name	202012590	214253684	218623438	219310757	229851531
Secondary	17.2	1.0	3.8	3.1	7.0
Th1 act
Secondary	0.0	1.1	10.5	8.2	14.3
Th2 act
Secondary	0.0	1.1	8.3	5.2	5.8
Tr1 act
Secondary	0.0	0.2	0.7	0.4	0.5
Th1 rest
Secondary	0.0	0.5	0.9	1.9	0.8
Th2 rest
Secondary	0.0	0.3	1.7	1.1	0.8
Tr1 rest
Primary	13.1	0.8	6.1	4.5	3.3
Th1 act
Primary	0.0	2.2	9.3	6.7	14.8
Th2 act
Primary	0.0	1.9	13.6	8.9	15.7
Tr1 act
Primary	0.0	0.8	5.7	1.7	0.8
Th1 rest
Primary	19.5	0.5	3.3	2.3	2.3
Th2 rest
Primary	40.6	1.8	8.6	7.2	4.8
Tr1 rest
CD45RA CD4	0.0	1.0	3.0	3.7	0.0
lymphocyte act
CD45RO CD4	0.0	2.3	12.7	11.2	16.2
lymphocyte act
CD8 lymphocyte	0.0	2.4	12.0	10.6	11.0
act
Secondary CD8	0.0	1.6	7.6	8.3	3.5
lymphocyte rest
Secondary CD8	0.0	0.5	1.0	1.4	1.1
lymphocyte act
CD4 lymphocyte	0.0	0.0	1.3	1.1	0.3
none
2ry Th1/Th2/	0.0	0.5	3.7	2.9	1.6
Tr1_anti-CD95
CH11
LAK cells rest	0.0	2.2	9.0	9.1	10.4
LAK cells IL-2	0.0	1.6	9.2	8.0	4.2
LAK cells	0.0	0.3	1.0	1.4	1.4
IL-2 + IL-12
LAK cells	0.0	0.7	2.3	1.2	2.8
IL-2 + IFN
gamma
LAK cells	22.1	0.5	5.5	4.7	0.6
IL-2 + IL-18
LAK cells	0.0	1.0	2.6	4.3	8.5
PMA/ionomycin
NK Cells IL-2	14.3	2.5	12.6	12.2	31.2
rest
Two Way MLR 3 day	8.5	0.9	3.7	4.1	3.1
Two Way MLR 5 day	0.0	0.9	6.2	2.4	4.0
Two Way MLR 7 day	0.0	1.3	5.7	3.0	3.9
PBMC rest	0.0	1.3	8.4	4.4	2.9
PBMC PWM	0.0	1.6	6.9	4.6	2.4
PBMC PHA-L	0.0	2.7	14.1	16.3	14.5
Ramos (B cell)	0.0	0.0	0.0	0.0	0.0
none
Ramos (B cell)	0.0	0.0	0.0	0.0	0.0
ionomycin
B lymphocytes PWM	0.0	2.0	7.5	8.8	5.6
B lymphocytes	37.4	2.7	17.1	13.0	15.4
CD40L and IL-4
EOL-1 dbcAMP	0.0	0.1	2.4	0.8	0.4
EOL-1 dbcAMP	0.0	0.0	0.4	0.8	0.8
PMA/ionomycin
Dendritic cells	0.0	1.5	12.2	5.7	9.5
none
Dendritic cells	0.0	0.4	0.4	1.1	1.1
LPS
Dendritic cells	0.0	1.6	11.0	10.0	6.5
anti-CD40
Monocytes rest	0.0	8.2	39.0	30.8	13.4
Monocytes LPS	0.0	1.4	9.6	5.3	4.4
Macrophages rest	7.3	8.1	42.3	33.0	12.1
Macrophages LPS	0.0	0.5	1.6	2.0	0.0
HUVEC none	15.3	3.9	16.6	19.6	32.3
HUVEC starved	19.9	7.3	48.3	32.3	55.1
HUVEC IL-1beta	34.4	9.3	54.3	51.1	80.7
HUVEC IFN gamma	46.7	9.9	57.4	50.0	97.9
HUVEC TNF	13.8	3.6	15.3	14.0	24.0
alpha + IFN
gamma
HUVEC TNF	0.0	3.0	17.1	14.6	19.5
alpha + IL4
HUVEC IL-11	0.0	4.7	27.0	25.0	41.8
Lung	0.0	1.1	7.3	6.5	15.6
Microvascular
EC none
Lung	16.4	100.0	7.4	4.4	4.2
Microvascular
EC
TNFalpha +
IL-1beta
Microvascular	18.3	0.9	4.3	4.0	5.0
Dermal EC none
Microsvasular	0.0	0.1	2.4	3.2	3.4
Dermal EC
TNFalpha +
IL-1beta
Bronchial	0.0	0.0	0.4	0.0	0.6
epithelium
TNFalpha +
IL1beta
Small airway	0.0	0.1	0.2	0.0	0.5
epithelium none
Small airway	0.0	0.0	1.0	0.6	0.0
epithelium
TNFalpha +
IL-1beta
Coronery artery	0.0	0.0	1.0	0.0	0.5
SMC rest
Coronery artery	0.0	0.1	0.5	1.1	1.5
SMC TNFalpha +
IL-1beta
Astrocytes rest	0.0	0.5	3.4	2.5	2.1
Astrocytes	0.0	0.5	1.9	2.1	1.1
TNFalpha + IL-
1beta
KU-812 (Basophil)	0.0	3.6	12.1	11.3	20.6
rest
KU-812 (Basophil)	0.0	4.3	14.9	17.3	27.9
PMA/ionomycin
CCD1106	0.0	0.2	1.1	1.3	1.0
(Keratinocytes)
none
CCD1106	0.0	0.2	1.0	1.1	0.9
(Keratinocytes)
TNFalpha +
IL-1beta
Liver cirrhosis	0.0	1.1	3.9	8.4	9.5
NCI-H292 none	14.4	0.5	0.9	1.7	3.4
NCI-H292 IL-4	41.8	1.1	7.7	1.8	3.3
NCI-H292 IL-9	22.2	1.9	8.1	7.8	4.2
NCI-H292 IL-13	0.0	1.0	7.0	2.3	6.8
NCI-H292 IFN	0.0	0.9	5.4	3.3	5.9
gamma
HPAEC none	0.0	7.5	58.2	40.6	54.3
HPAEC TNF	9.5	6.9	35.1	29.9	59.0
alpha +
IL-1 beta
Lung fibroblast	0.0	0.1	0.0	0.0	0.5
none
Lung fibroblast	0.0	0.2	0.0	0.0	0.4
TNF alpha +
IL-1 beta
Lung fibroblast	0.0	0.0	0.0	0.0	1.2
IL-4
Lung fibroblast	0.0	0.0	0.4	0.0	0.0
IL-9
Lung fibroblast	0.0	0.0	0.5	0.0	0.8
IL-13
Lung fibroblast	0.0	0.1	0.5	0.0	0.0
IFN gamma
Dermal fibroblast	0.0	0.2	0.6	0.9	1.2
CCD1070 rest
Dermal fibroblast	0.0	1.4	8.0	5.6	8.8
CCD1070
TNF alpha
Dermal fibroblast	0.0	0.1	1.0	1.6	5.3
CCD1070 IL-
1 beta
Dermal fibroblast	0.0	0.2	0.5	0.4	1.3
IFN gamma
Dermal fibroblast	0.0	0.0	0.4	0.3	1.9
IL-4
Dermal	0.0	0.0	0.8	0.3	1.0
Fibroblasts rest
Neutrophils	0.0	0.3	0.7	0.0	0.8
TNFa + LPS
Neutrophils rest	0.0	2.2	12.3	13.2	12.6
Colon	0.0	0.6	2.6	2.4	1.9
Lung	51.1	2.1	8.5	9.0	1.2
Thymus	0.0	3.5	19.1	22.7	1.2
Kidney	100.0	18.8	100.0	100.0	100.0

[0659]

TABLE BL
Panel 5 Islet
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4712,		Ag4712,
	Run		Run
Tissue Name	225052652	Tissue Name	225052652
97457_Patient-02go_adipose	0.0	94709_Donor 2 AM - A_adipose	0.0
97476_Patient-07sk_skeletal	0.0	94710_Donor 2 AM - B_adipose	0.0
muscle
97477_Patient-07ut_uterus	0.0	94711_Donor 2 AM - C_adipose	0.0
97478_Patient-07pl_placenta	100.0	94712_Donor 2 AD - A_adipose	0.0
99167_Bayer Patient 1	0.0	94713_Donor 2 AD - B_adipose	0.0
97482_Patient-08ut_uterus	0.0	94714_Donor 2 AD - C_adipose	0.0
97483_Patient-08pl_placenta	0.0	94742_Donor 3 U - A_Mesenchymal	0.0
		Stem Cells
97486_Patient-09sk_skeletal	0.0	94743_Donor 3 U - B_Mesenchymal	0.0
muscle		Stem Cells
97487_Patient-09ut_uterus	0.0	94730_Donor 3 AM - A_adipose	0.0
97488_Patient-09pl_placenta	0.0	94731_Donor 3 AM - B_adipose	0.0
97492_Patient-10ut_uterus	0.0	94732_Donor 3 AM - C_adipose	0.0
97493_Patient-10pl_placenta	0.0	94733_Donor 3 AD - A_adipose	0.0
97495_Patient-11go_adipose	31.2	94734_Donor 3 AD - B_adipose	0.0
97496_Patient-11sk_skeletal	0.0	94735_Donor 3 AD - C_adipose	0.0
muscle
97497_Patient-11ut_uterus	0.0	77138_Liver_HepG2untreated	30.6
97498_Patient-11pl_placenta	35.4	73556_Heart_Cardiac stromal cells	0.0
		(primary)
97500_Patient-12go_adipose	0.0	81735_Small Intestine	0.0
97501_Patient-12sk_skeletal	35.4	72409_Kidney_Proximal Convoluted	0.0
muscle			Tubule
97502_Patient-12ut_uterus	63.7	82685_Small intestine_Duodenum	26.8
97503_Patient-12pl_placenta	0.0	90650_Adrenal_Adrenocortical adenoma	0.0
94721_Donor 2 U -	0.0	72410_Kidney_HRCE	34.4
A_Mesenchymal Stem Cells
94722_Donor 2 U -	0.0	74211_Kidney_HRE	0.0
B_Mesenchymal Stem Cells
94723_Donor 2 U -	35.6	73139_Uterus_Uterine smooth muscle	0.0
C_Mesenchymal Stem Cells

[0660]

TABLE BM
general oncology screening panel_v_2.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4940,		Ag4940,
	Run		Run
Tissue Name	260281953	Tissue Name	260281953
Colon cancer 1	3.7	Bladder NAT 2	0.1
Colon NAT 1	1.1	Bladder NAT 3	0.1
Colon cancer 2	1.3	Bladder NAT 4	0.2
Colon NAT 2	7.9	Prostate adenocarcinoma 1	5.0
Colon cancer 3	7.9	Prostate adenocarcinoma 2	0.8
Colon NAT 3	10.2	Prostate adenocarcinoma 3	5.1
Colon malignant cancer 4	5.0	Prostate adenocarcinoma 4	1.2
Colon NAT 4	1.2	Prostate NAT 5	4.9
Lung cancer 1	7.8	Prostate adenocarcinoma 6	2.2
Lung NAT 1	0.7	Prostate adenocarcinoma 7	3.0
Lung cancer 2	28.3	Prostate adenocarcinoma 8	1.3
Lung NAT 2	1.5	Prostate adenocarcinoma 9	4.2
Squamous cell carcinoma 3	4.3	Prostate NAT 10	0.4
Lung NAT 3	0.4	Kidney cancer 1	8.8
Metastatic melanoma 1	13.3	Kidney NAT 1	3.4
Melanoma 2	0.6	Kidney cancer 2	100.0
Melanoma 3	0.4	Kidney NAT 2	12.6
Metastatic melanoma 4	9.2	Kidney cancer 3	31.6
Metastatic melanoma 5	3.9	Kidney NAT 3	9.9
Bladder cancer 1	0.3	Kidney cancer 4	12.9
Bladder NAT 1	0.0	Kidney NAT 4	7.5
Bladder cancer 2	0.5

[0661] AI_comprehensive panel_v1.0 Summary: Ag4940 Highest expression of this gene is seen in an asthma derived sample (CT=28.1). In addition, moderate levels of expression are evident in a cluster of asthma derived samples. Thus, this gene product may be involved in the pathogenesis of this disease.

[0662] CNS_neurodegeneration_v1.0 Summary: Ag5250 This expression profile confirms the presence of this gene in the brain at high to moderate levels. See Panel 1.4 for discussion of this gene in the central nervous system.

[0663] Ag4554/Ag4712/Ag5249 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0664] General_screening_panel_v1.4 Summary: Ag4940 Two experiments with the same probe and primer produce results that are in excellent agreement. Highest expression of this gene is detected in ovarian cancer SK-OV-3 cell line (CTs=26-27). Moderate levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, melanoma and brain cancers.

[0665] This gene codes for asparaginase protein. Certain malignant cells, including those of many acute lymphoblastic leukaemias(ALL), lack asparagine synthetase (ASNS) and therefore depend on exogenous L-asparagine (Cooney, D. A. & Handschumacher, R. E. 1970, Annu. Rev. Pharmacol. 10, 421-440). This observation has been therapeutically exploited through the use of bacterial asparaginase for the treatment of ALL for almost 30 years (Gallagher et al., 1989, Asparaginase as a drug for treatment of acute lymphoblastic leukemia. Essays Biochem 24:1-40, PMID: 2676522). There are currently three different asparaginases available for clinical use:

[0666] 1. E.coli-derived (Elspar),

[0667] 2. E.coli-derived/pegylated (Oncaspar), and

[0668] 3. Erwinia chrysanthemi-derived (Erwinase).

[0669] When used alone as a cancer therapeutic, asparaginase is not very effective as evidenced by high rates of tumor recurrence. However, clinical trials have confirmed the eminent value of asparaginase in the combination chemotherapy of ALL and of some subtypes of non-Hodgkin lymphoma, and its important role as an essential component of multimodal treatment protocols (Muller H J, Boos J., 1998, Crit Rev Oncol Hematol 28(2):97-113). Despite the unique mechanism of action of this cytotoxic substance which shows relative selectivity with regard to the metabolism of malignant cells, some patients experience toxic effects during asparaginase therapy. This problem has been largely (but not completely) solved with the pegylated form of asparaginase (Holle L M, 1997, Ann Pharmacother 31(5):616-24). Some efforts have been made to expand the spectrum of tumors that may respond to asparaginase treatment beyond the leukemias. However, early clinical trials done with solid tumours have shown only occasional responses to L-asparaginase in melanoma, chronic granulocytic leukaemia,lymphosarcoma and reticulum cell sarcoma43, but not in other tumour types (Scherf et al., 2000, 24(3):236-244). Furthermore, it was shown that that cell lines derived from most solid tumors had higher levels of asparagine synthetase and the sensitivity of tumor cells to asparaginase is inversely related to their level of ASNS (Scherf et al., 2000, 24(3):236-244). Thus, the asperginase encoded by this gene may be useful in the treatment of ALL, non-Hodgkin lymphoma and solid tumors that exhibit low/negligible levels of ASNS.

[0670] Among tissues with metabolic or endocrine function, this gene is expressed at moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0671] In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0672] In another experiment with probe Ag4712, highest expression of this gene is detected in normal breast sample (CT=32.9) and low to moderate levels of expression is also seen in all the regions of the brain, and in some of the cancer cell lines derived from brain, colon, gastric, lung, and ovarian cancer.

[0673] Ag4552 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0674] General_screening_panel_v1.5 Summary: Ag5250 Highest expression of this gene is detected in ovarian cancer SK-OV-3 cell line (CT=25.3). High expression of this gene is also seen in number of cancer cell lines derived from pancreatic, liver, brain, colon, gastric, renal, lung, breast, ovarian, squamous cell carcinoma, melanoma and prostate cancer. In addition, high expression of this gene is also seen in all the regions of central nervous system examined including including amygdala, hippocampus, substantia nigra, thalamus, cerebral cortex, and spinal cord, as well as in tissues with metabolic function such as adipose, pancreas, thyroid, pituitary and adrenal gland, skeletal muscle, heart, liver and gastrointestinal tract.

[0675] Interestingly, expression of this gene is higher in fetal (CTs=29-31) as compared to adult lung and liver (CTs=35). Therefore, expression of this gene may be used to distinguish between these fetal and adult tissues. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein may enhance growth or development of lung and liver in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of lung and liver related diseases. See panel 1.4 for further discussion of this gene.

[0676] Oncology_cell_line_screening_panel_v3.1 Summary: Ag4940 Highest expression of this gene is seen in small lung carcinoma sample (CT=27). Moderate to low levels of expression of this gene is seen in a wide range of cell lines derived from bladder, tongue, bone, vulva, pancreatic, kidney, cervical, ovarian, uterine, gastric, colon, lung, and brain cancers. In addition, significant expression of this gene is also seen in B cell and T cell lymphomas. Therefore, therapeutic modulation of this gene product may be useful in the treatment of B cell and T cell lymphomas, bladder, tongue, bone, vulva, pancreatic, kidney, cervical, ovarian, uterine, gastric, colon, lung, and brain cancers. See panel 1.4 for further discussion on this gene.

[0677] Panel 4.1D Summary: Ag4940/Ag5250 Results from four experiments with two different probe and primer sets are in excellent agreement with highest expression of this gene in kidney and cytokine treated lung microvascular endothelial cells (CTs=27-30.6). Moderate to low levels of expression of this gene is also seen in endothelial cells, cytokine activated NCI-H292 cells, basophils, anti-CD40 stimulated dendritic cells, cytokine treated B lymphocytes, PBMC cells, T lymphocytes prepared under a number of conditions, lymphokine activated killer cells (LAK) and NK cells, dendritic cells, monocytes, and macrophages. Dendritic cells and macrophages are powerful antigen-presenting cells (APC) whose function is pivotal in the initiation and maintenance of normal immune responses. Autoimmunity and inflammation may also be reduced by suppression of this function. Therefore, small molecule drugs that antagonzie the function of this gene product may reduce or eliminate the symptoms in patients with several types of autoimmune and inflammatory diseases, such as lupus erythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, or psoriasis. In another experiment with probe Ag4712 low levels of expression of this gene is restricted to kidney (CT=34). Therefore, expression of this gene may be used to differentiate kidney from other samples used in this panel.

[0678] Ag4552/Ag5249/Ag4712(Run 223211818) Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0679] Panel 5 Islet Summary: Ag4552/Ag4712 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0680] Panel 5D Summary: Ag4712 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0681] general oncology screening panel_v—2.4 Summary: Ag4940 Highest expression of this gene is detected in kidney cancer (CT=27.7). Expression of this gene is higher in the kidney and lung cancer sample (CTs=27-29) as compared to adjacent control sample (CT=30-33). Therefore, expression of this gene may be used to differentiate cancer from the corresponding normal samples and also as marker for detection of kidney and lung cancers. In addition, moderate to low levels of expression of this gene is also seen in normal and cancer samples derived from colon, lung, metastatic melanoma, prostate and kidney. Therefore, therapeutic modulation of the expression of this gene or protein encoded by this gene may be useful in the treatment of metastatic melanoma, colon, lung, kidney and prostate cancers.

[0682] C. CG109541-01: Olfactory Receptor-Like Protein

[0683] Expression of gene CG109541-01 was assessed using the primer-probe set Ag4391, described in Table CA.

TABLE CA
Probe Name Ag4391
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggaccagctaatttcagtgaca-3′	22	879	169
Probe	TET-5′-caccgtctttactccactacttaatcctg-3′-TAMRA	29	903	170
Reverse	5′-acctccttgttcctcaaagtgt-3′	22	938	171

[0684] CNS_neurodegeneration_v1.0 Summary: Ag4391 Expression of the CG109541-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0685] General_screening_panel_v1.4 Summary: Ag4391 Expression of the CG109541-01 gene is low/undetectable (CTs>35) across all of the samples on this panel. This gene codes for an olfactory receptor, a member of G protein-coupled receptor (GPCR) family. Based on analogy to other odorant receptor genes, we predict that expression of this gene may be highest in nasal epithelium, a sample not represented in this panel.

[0686] Panel 4.1D Summary: Ag4391 Expression of the CG109541-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0687] Panel 5D Summary: Ag4391 Expression of the CG109541-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0688] Panel CNS—1 Summary: Ag4391 Expression of the CG109541-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0689] Panel CNS—1.1 Summary: Ag4391 Expression of the CG109541-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0690] D. CG110223-01 and CG110223-03: Glycosyltransferase

[0691] Expression of gene CG110223-01 and CG110223-03 was assessed using the primer-probe set Ag4414 described in Table DA. Expression of gene CG110223-03 was assessed using the primer-probe set Ag6795 described in Table DB. Results of the RTQ-PCR runs are shown in Tables DC, DD, DE and DF.

TABLE DA
Probe Name Ag4414
			Start	SEQ ID
Primers	Sequences	Length	Position	No+HZ,1/45
Forward	5′-acacatccaaactggacattgt-3′	22	933	172
Probe	TET-5′-taatggttttcctgatcttgccgcat-3′-TAMRA	26	960	173
Reverse	5′-gcagtatggggatcacattaag-3′	22	988	174

[0692]

TABLE DB
Probe Name Ag6795
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gactatttggaaggaagattttga-3′	24	322	175
Probe	TET-5′-tgtagataatacactgtccttcccagtttcctt-3′-TAMRA	33	352	176
Reverse	5′-gcgcatgagttactgtgatg-3′	20	396	177

[0693]

TABLE DC
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4414,		Ag4414,
	Run		Run
Tissue Name	224505963	Tissue Name	224505963
AD 1 Hippo	26.4	Control (Path) 3 Temporal Ctx	21.9
AD 2 Hippo	36.9	Control (Path) 4 Temporal Ctx	29.9
AD 3 Hippo	18.0	AD 1 Occipital Ctx	45.1
AD 4 Hippo	16.4	AD 2 Occipital Ctx (Missing)	0.0
AD 5 Hippo	63.3	AD 3 Occipital Ctx	17.7
AD 6 Hippo	85.9	AD 4 Occipital Ctx	34.2
Control 2 Hippo	43.5	AD 5 Occipital Ctx	59.0
Control 4 Hippo	18.8	AD 6 Occipital Ctx	43.5
Control (Path) 3 Hippo	12.5	Control 1 Occipital Ctx	11.1
AD 1 Temporal Ctx	55.9	Control 2 Occipital Ctx	52.5
AD 2 Temporal Ctx	37.1	Control 3 Occipital Ctx	31.2
AD 3 Temporal Ctx	19.1	Control 4 Occipital Ctx	15.2
AD 4 Temporal Ctx	40.3	Control (Path) 1 Occipital Ctx	74.7
AD 5 Inf Temporal Ctx	100.0	Control (Path) 2 Occipital Ctx	22.4
AD 5 Sup Temporal Ctx	76.3	Control (Path) 3 Occipital Ctx	24.1
AD 6 Inf Temporal Ctx	74.7	Control (Path) 4 Occipital Ctx	20.4
AD 6 Sup Temporal Ctx	73.2	Control 1 Parietal Ctx	11.0
Control 1 Temporal Ctx	9.9	Control 2 Parietal Ctx	64.6
Control 2 Temporal Ctx	39.0	Control 3 Parietal Ctx	21.5
Control 3 Temporal Ctx	16.4	Control (Path) 1 Parietal Ctx	48.0
Control 3 Temporal Ctx	12.4	Control (Path) 2 Parietal Ctx	33.2
Control (Path) 1 Temporal Ctx	31.6	Control (Path) 3 Parietal Ctx	25.3
Control (Path) 2 Temporal Ctx	33.9	Control (Path) 4 Parietal Ctx	37.1

[0694]

TABLE DD
General_screening_panel_v1.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4414,		Ag4414,
	Run		Run
Tissue Name	219923154	Tissue Name	219923154
Adipose	5.9	Renal ca. TK-10	0.0
Melanoma* Hs688(A).T	0.0	Bladder	2.4
Melanoma* Hs688(B).T	0.3	Gastric ca. (liver met.) NCI-N87	0.8
Melanoma* M14	66.4	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	2.6	Colon ca. SW-948	0.1
Melanoma* SK-MEL-5	52.1	Colon ca. SW480	0.1
Squamous cell carcinoma SCC-4	0.1	Colon ca.* (SW480 met) SW620	0.0
Testis Pool	0.6	Colon ca. HT29	0.2
Prostate ca.* (bone met) PC-3	0.0	Colon ca. HCT-116	2.9
Prostate Pool	1.4	Colon ca. CaCo-2	35.8
Placenta	0.4	Colon cancer tissue	1.7
Uterus Pool	6.5	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	1.5	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.2	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.9	Colon Pool	16.8
Ovarian ca. OVCAR-5	2.5	Small Intestine Pool	7.0
Ovarian ca. IGROV-1	1.2	Stomach Pool	6.6
Ovarian ca. OVCAR-8	1.5	Bone Marrow Pool	2.2
Ovary	3.5	Fetal Heart	5.8
Breast ca. MCF-7	0.0	Heart Pool	3.9
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	13.1
Breast ca. BT 549	7.2	Fetal Skeletal Muscle	1.8
Breast ca. T47D	4.0	Skeletal Muscle Pool	3.3
Breast ca. MDA-N	44.1	Spleen Pool	2.6
Breast Pool	13.8	Thymus Pool	6.1
Trachea	2.2	CNS cancer (glio/astro) U87-MG	0.2
Lung	0.9	CNS cancer (glio/astro) U-118-MG	4.8
Fetal Lung	19.2	CNS cancer (neuro;met) SK-N-AS	43.8
Lung ca. NCI-N417	0.5	CNS cancer (astro) SF-539	0.7
Lung ca. LX-1	0.7	CNS cancer (astro) SNB-75	1.7
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	0.9
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	7.4
Lung ca. A549	1.0	Brain (Amygdala) Pool	8.1
Lung ca. NCI-H526	11.8	Brain (cerebellum)	3.4
Lung ca. NCI-H23	0.1	Brain (fetal)	10.2
Lung ca. NCI-H460	2.3	Brain (Hippocampus) Pool	10.4
Lung ca. HOP-62	0.1	Cerebral Cortex Pool	14.2
Lung ca. NCI-H522	0.0	Brain (Substantia nigra) Pool	14.9
Liver	0.1	Brain (Thalamus) Pool	16.4
Fetal Liver	5.4	Brain (whole)	6.1
Liver ca. HepG2	0.0	Spinal Cord Pool	23.2
Kidney Pool	8.0	Adrenal Gland	2.1
Fetal Kidney	100.0	Pituitary gland Pool	4.3
Renal ca. 786-0	0.3	Salivary Gland	0.4
Renal ca. A498	1.0	Thyroid (female)	9.8
Renal ca. ACHN	0.7	Pancreatic ca. CAPAC2	0.4
Renal ca. UO-31	1.7	Pancreas Pool	9.5

[0695]

TABLE DE
Panel CNS_1.1
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4414,		Ag4414,
	Run		Run
Tissue Name	195308644	Tissue Name	195308644
Cing Gyr Depression2	28.9	BA17 PSP2	5.8
Cing Gyr Depression	12.4	BA17 PSP	18.9
Cing Gyr PSP2	6.2	BA17 Huntington's2	27.5
Cing Gyr PSP	40.9	BA17 Huntington's	22.7
Cing Gyr Huntington's2	30.8	BA17 Parkinson's2	30.1
Cing Gyr Huntington's	81.8	BA17 Parkinson's	38.7
Cing Gyr Parkinson's2	38.4	BA17 Alzheimer's2	6.5
Cing Gyr Parkinson's	57.4	BA17 Control2	37.4
Cing Gyr Alzheimer's2	10.8	BA17 Control	28.7
Cing Gyr Alzheimer's	31.6	BA9 Depression2	10.7
Cing Gyr Control2	19.2	BA9 Depression	6.5
Cing Gyr Control	41.5	BA9 PSP2	3.7
Temp Pole Depression2	6.6	BA9 PSP	15.0
Temp Pole PSP2	1.1	BA9 Huntington's2	15.9
Temp Pole PSP	1.5	BA9 Huntington's	44.8
Temp Pole Huntington's	17.8	BA9 Parkinson's2	26.8
Temp Pole Parkinson's2	12.3	BA9 Parkinson's	26.6
Temp Pole Parkinson's	21.3	BA9 Alzheimer's2	9.4
Temp Pole Alzheimer's2	0.0	BA9 Alzheimer's	0.0
Temp Pole Alzheimer's	3.2	BA9 Control2	41.2
Temp Pole Control2	26.4	BA9 Control	16.4
Temp Pole Control	6.4	BA7 Depression	10.1
Glob Palladus Depression	6.0	BA7 PSP2	19.5
Glob Palladus PSP2	3.6	BA7 PSP	41.5
Glob Palladus PSP	6.0	BA7 Huntington's2	55.5
Glob Palladus Parkinson's2	46.0	BA7 Huntington's	32.3
Glob Palladus Parkinson's	83.5	BA7 Parkinson's2	26.4
Glob Palladus Alzheimer's2	20.0	BA7 Parkinson's	16.3
Glob Palladus Alzheimer's	16.4	BA7 Alzheimer's2	3.7
Glob Palladus Control2	18.0	BA7 Control2	33.0
Glob Palladus Control	28.5	BA7 Control	13.1
Sub Nigra Depression2	15.5	BA4 Depression2	8.0
Sub Nigra Depression	36.1	BA4 Depression	18.7
Sub Nigra PSP2	4.5	BA4 PSP2	9.4
Sub Nigra Huntington's2	97.3	BA4 PSP	4.4
Sub Nigra Huntington's	95.9	BA4 Huntington's2	6.4
Sub Nigra Parkinson's2	100.0	BA4 Huntington's	20.3
Sub Nigra Alzheimer's2	34.4	BA4 Parkinson's	43.5
Sub Nigra Control2	47.3	BA4 Parkinson's	57.0
Sub Nigra Control	69.7	BA4 Alzheimer's2	6.4
BA17 Depression2	33.7	BA4 Control2	35.8
BA17 Depression	20.7	BA4 Control	19.9

[0696]

TABLE DF
general oncology screening panel_v_2.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4414,		Ag4414,
	Run		Run
Tissue Name	260285437	Tissue Name	260285437
Colon cancer 1	4.2	Bladder NAT 2	0.8
Colon NAT 1	3.5	Bladder NAT 3	0.3
Colon cancer 2	5.0	Bladder NAT 4	6.7
Colon NAT 2	5.4	Prostate adenocarcinoma 1	14.0
Colon cancer 3	13.3	Prostate adenocarcinoma 2	1.1
Colon NAT 3	28.3	Prostate adenocarcinoma 3	4.3
Colon malignant cancer 4	6.7	Prostate adenocarcinoma 4	12.4
Colon NAT 4	4.7	Prostate NAT 5	3.6
Lung cancer 1	1.4	Prostate adenocarcinoma 6	0.8
Lung NAT 1	2.0	Prostate adenocarcinoma 7	2.1
Lung cancer 2	53.2	Prostate adenocarcinoma 8	1.1
Lung NAT 2	5.0	Prostate adenocarcinoma 9	4.4
Squamous cell carcinoma 3	6.0	Prostate NAT 10	0.8
Lung NAT 3	2.2	Kidney cancer 1	16.8
Metastatic melanoma 1	28.1	Kidney NAT 1	27.7
Melanoma 2	1.1	Kidney cancer 2	45.1
Melanoma 3	2.6	Kidney NAT 2	100.0
Metastatic melanoma 4	42.0	Kidney cancer 3	17.7
Metastatic melanoma 5	45.7	Kidney NAT 3	53.2
Bladder cancer 1	2.4	Kidney cancer 4	36.3
Bladder NAT 1	0.0	Kidney NAT 4	10.1
Bladder cancer 2	3.3

[0697] CNS_neurodegeneration_v1.0 Summary: Ag4414 This panel confirms the expression of the CG110223-01 gene at low levels in the brain in an independent group of individuals. This gene is found to be slightly upregulated (p=0.05) in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of the expression or function of this gene may decrease neuronal death and be of use in the treatment of this disease.

[0698] Ag6795 Expression of the CG110223-03 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0699] General_screening_panel_v1.4 Summary: Ag4414 Highest expression of the CG110223-01 gene is detected in fetal kidney (CT=26.2). Interestingly, expression of this gene is higher in fetal as compared to adult kidney (CT=29.9). Therefore, expression of this gene can be used to distinguish fetal from adult kidney. In addition, the relative overexpression of this gene in fetal kidney suggests that the protein product may enhance kidney growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of kidney related diseases.

[0700] High to moderate levels of expression of this gene is also seen in number of cancer cell lines derived from gastric, colon, lung, renal, breast, ovarian, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of gastric, colon, lung, renal, breast, ovarian, melanoma and brain cancers.

[0701] Among tissues with metabolic or endocrine function, this gene is expressed at moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0702] In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0703] General_screening_panel_v1.6 Summary: Ag6795 Expression of the CG110223-03 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0704] Ag6795 Expression of the CG110223-03 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0705] Panel CNS—1.1 Summary: Ag4414 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. See Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.

[0706] general oncology screening panel_v—2.4 Summary: Ag4414 Highest expression of the CG110223-01 gene is detected in kidney sample (CT=30). Moderate to low expression of this gene is also seen in number of cancer samples derived from metastatic melanoma, kidney, prostate, lung, and colon cancers. Therefore, therapeutic modulation of this gene may be useful in the treatment of these cancers.

[0707] E. CG110223-02: Alpha-N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase

[0708] Expression of gene CG110223-02 was assessed using the primer-probe set Ag6786, described in Table EA. Results of the RTQ-PCR runs are shown in Tables EB and EC.

TABLE EA
Probe Name Ag6786
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ctgggaaggacagagtccagt-3′	21	629	178
Probe	TET-5′-atatctcagcacagggtggtttaccttccttc-3′-TAMRA	32	657	179
Reverse	5′-gccataacaggcgtccat-3′	18	694	180

[0709]

TABLE EB
CNR neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6786,		Ag6786,
	Run		Run
Tissue Name	277731706	Tissue Name	277731706
AD 1 Hippo	33.4	Control (Path) 3 Temporal Ctx	22.4
AD 2 Hippo	38.7	Control (Path) 4 Temporal Ctx	21.9
AD 3 Hippo	11.6	AD 1 Occipital Ctx	41.5
AD 4 Hippo	10.6	AD 2 Occipital Ctx (Missing)	0.0
AD 5 hippo	58.6	AD 3 Occipital Ctx	9.3
AD 6 Hippo	75.3	AD 4 Occipital Ctx	27.7
Control 2 Hippo	45.1	AD 5 Occipital Ctx	47.3
Control 4 Hippo	10.2	AD 6 Occipital Ctx	53.6
Control (Path) 3 Hippo	27.2	Control 1 Occipital Ctx	12.3
AD 1 Temporal Ctx	53.2	Control 2 Occipital Ctx	55.5
AD 2 Temporal Ctx	42.3	Control 3 Occipital Ctx	19.9
AD 3 Temporal Ctx	9.5	Control 4 Occipital Ctx	8.8
AD 4 Temporal Ctx	31.2	Control (Path) 1 Occipital Ctx	60.7
AD 5 Inf Temporal Ctx	100.0	Control (Path) 2 Occipital Ctx	14.5
AD 5 SupTemporal Ctx	66.0	Control (Path) 3 Occipital Ctx	19.9
AD 6 Inf Temporal Ctx	67.4	Control (Path) 4 Occipital Ctx	21.3
AD 6 Sup Temporal Ctx	76.3	Control 1 Parietal Ctx	11.4
Control 1 Temporal Ctx	10.9	Control 2 Parietal Ctx	57.0
Control 2 Temporal Ctx	42.9	Control 3 Parietal Ctx	13.8
Control 3 Temporal Ctx	17.0	Control (Path) 1 Parietal Ctx	36.9
Control 4 Temporal Ctx	5.6	Control (Path) 2 Parietal Ctx	40.9
Control (Path) 1 Temporal Ctx	39.0	Control (Path) 3 Parietal Ctx	24.3
Control (Path) 2 Temporal Ctx	25.5	Control (Path) 4 Parietal Ctx	32.1

[0710]

TABLE EC
General_screening_panel_v1.6
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6786,		Ag6786,
	Run		Run
Tissue Name	277640786	Tissue Name	277640786
Adipose	10.6	Renal ca. TK-10	0.1
Melanoma* Hs688(A).T	0.0	Bladder	2.0
Melanoma* Hs688(B).T	0.2	Gastric ca. (liver met.) NCI-N87	1.6
Melanoma* M14	90.1	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	4.9	Colon ca. SW-948	0.1
Melanoma* SK-MEL-5	54.0	Colon ca. SW480	0.2
Squamous cell carcinoma SCC-4	0.2	Colon ca.* (SW480 met) SW620	0.0
Testis Pool	0.6	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.0	Colon ca. HCT-116	2.6
Prostate Pool	1.2	Colon ca. CaCo-2	43.5
Placenta	0.4	Colon cancer tissue	1.6
Uterus Pool	4.2	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	1.3	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.4	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	1.4	Colon Pool	19.9
Ovarian ca. OVCAR-5	4.1	Small Intestine Pool	6.2
Ovarian ca. IGROV-1	0.4	Stomach Pool	4.1
Ovarian ca. OVCAR-8	2.0	Bone Marrow Pool	1.3
Ovary	4.1	Fetal Heart	3.0
Breast ca. MCF-7	0.0	Heart Pool	3.4
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	17.4
Breast ca. BT 549	13.2	Fetal Skeletal Muscle	2.2
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.6
Breast ca. MDA-N	25.5	Spleen Pool	2.2
Breast Pool	17.7	Thymus Pool	6.2
Trachea	2.4	CNS cancer (glio/astro) U87-MG	0.1
Lung	1.1	CNS cancer (glio/astro) U-118-MG	6.8
Fetal Lung	18.6	CNS cancer (neuro;met) SK-N-AS	55.1
Lung ca. NCI-N417	0.6	CNS cancer (astro) SF-539	1.4
Lung ca. LX-1	0.4	CNS cancer (astro) SNB-75	1.8
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	1.0
Lung ca. SHP-77	0.1	CNS cancer (glio) SF-295	11.8
Lung ca. A549	1.3	Brain (Amygdala) Pool	8.4
Lung ca. NCI-H526	12.1	Brain (cerebellum)	22.2
Lung ca. NCI-H23	0.2	Brain (fetal)	13.8
Lung ca. NCI-H460	2.9	Brain (Hippocampus) Pool	13.0
Lung ca. HOP-62	0.2	Cerebral Cortex Pool	12.4
Lung ca. NCI-H522	0.0	Brain (Substantia nigra) Pool	7.2
Liver	0.7	Brain (Thalamus) Pool	13.5
Fetal Liver	4.8	Brain (whole)	8.5
Liver ca. HepG2	0.0	Spinal Cord Pool	23.3
Kidney Pool	11.8	Adrenal Gland	4.2
Fetal Kidney	100.0	Pituitary gland Pool	3.0
Renal ca. 786-0	0.1	Salivary Gland	0.2
Renal ca. A498	1.1	Throid (female)	14.6
Renal ca. ACHN	1.2	Pancreatic ca. CAPAN2	0.7
Renal ca. UO-31	3.8	Pancreas Pool	1.2

[0711] CNS_neurodegeneration_v1.0 Summary: Ag6786 This panel confirms the expression of the CG110223-02 gene at low levels in the brain in an independent group of individuals. This gene is found to be slightly upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of the expression or function of this gene may decrease neuronal death and be of use in the treatment of this disease.

[0712] General_screening_panel_v1.6 Summary: Ag6786 Highest expression of the CG110223-02 gene is detected in fetal kidney (CT=26.2). Interestingly, expression of this gene is higher in fetal (CTs=26-29.6) as compared to adult kidney and lung (CTs=30-33.7). Therefore, expression of this gene can be used to distinguish fetal from adult kidney and lung, respectively. In addition, the relative overexpression of this gene in fetal tissues suggests that the protein product may enhance growth or development of kidney and lung in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of kidney and lung related diseases.

[0713] High to moderate levels of expression of this gene is also seen in number of cancer cell lines derived from gastric, colon, lung, renal, breast, ovarian, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of gastric, colon, lung, renal, breast, ovarian, melanoma and brain cancers.

[0714] Among tissues with metabolic or endocrine function, this gene is expressed at moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0715] In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0716] F. CG110311-01: Mannosidase

[0717] Expression of gene CG110311-01 was assessed using the primer-probe set Ag4416, described in Table FA. Results of the RTQ-PCR runs are shown in Tables FB, FC, FD and FE.

TABLE FA
Probe Name Ag4416
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gggacagcttgtgactgagat-3′	21	2037	181
Probe	TET-5′-ccggcagtacttctacaggaacatgaca-3′-TAMRA	28	2058	182
Reverse	5′-cggattgcatacgtgtaattct-3′	22	2090	183

[0718]

TABLE FB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)	Exp. (%)
	Ag4416,	Ag4416,
	Run		Run
Tissue Name	224506018	Tissue Name	224506018
AD 1 Hippo	24.0	Control (Path) 3 Temporal Ctx	12.9
AD 2 Hippo	41.5	Control (Path) 4 Temporal Ctx	54.0
AD 3 Hippo	13.1	AD 1 Occipital Ctx	20.6
AD 4 Hippo	13.2	AD 2 Occipital Ctx (Missing)	0.0
AD 5 Hippo	100.0	AD 3 Occipital Ctx	11.7
AD 6 Hippo	44.1	AD 4 Occipital Ctx	26.2
Control 2 Hippo	47.3	AD 5 Occipital Ctx	76.3
Control 4 Hippo	17.0	AD 6 Occipital Ctx	24.0
Control (Path) 3 Hippo	13.1	Control 1 Occipital Ctx	9.4
AD 1 Temporal Ctx	32.1	Control 2 Occipital Ctx	87.1
AD 2 Temporal Ctx	55.5	Control 3 Occipital Ctx	24.5
AD 3 Temporal Ctx	12.2	Control 4 Occipital Ctx	12.7
AD 4 Temporal Ctx	50.0	Control (Path) 1 Occipital Ctx	97.3
AD 5 Inf Temporal Ctx	94.0	Control (Path) 2 Occipital Ctx	15.6
AD 5 Sup Temporal Ctx	56.3	Control (Path) 3 Occipital Ctx	7.9
AD 6 Inf Temporal Ctx	48.0	Control (Path) 4 Occipital Ctx	23.5
AD 6 Sup Temporal Ctx	47.6	Control 1 Parietal Ctx	17.9
Control 1 Temporal Ctx	14.0	Control 2 Parietal Ctx	50.3
Control 2 Temporal Ctx	82.4	Control 3 Parietal Ctx	27.0
Control 3 Temporal Ctx	0.1	Control (Path) 1 Parietal Ctx	98.6
Control 3 Temporal Ctx	6.0	Control (Path) 2 Parietal Ctx	37.6
Control (Path) 1 Temporal Ctx	77.9	Control (Path) 3 Parietal Ctx	8.8
Control (Path) 2 Temporal Ctx	58.6	Control (Path) 4 Parietal Ctx	66.9

[0719]

TABLE FC
General_screening_panel_v1.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4416,		Ag4416,
	Run		Run
Tissue Name	219923155	Tissue Name	219923155
Adipose	12.5	Renal ca. TK-10	16.7
Melanoma* Hs688(A).T	51.8	Bladder	22.5
Melanoma* Hs688(B).T	45.4	Gastric ca. (liver met.) NCI-N87	58.2
Melanoma* M14	23.3	Gastric ca. KATO III	50.0
Melanoma* LOXIMVI	17.8	Colon ca. SW-948	13.6
Melanoma* SK-MEL-5	18.7	Colon ca. SW480	33.2
Squamous cell carcinoma SCC-4	13.5	Colon ca.* (SW480 met) SW620	18.6
Testis Pool	7.2	Colon ca. HT29	23.5
Prostate ca.* (bone met) PC-3	6.7	Colon ca. HCT-116	28.7
Prostate Pool	12.2	Colon ca. CaCo-2	15.6
Placenta	14.6	Colon cancer tissue	12.8
Uterus Pool	9.8	Colon ca. SW1116	9.7
Ovarian ca. OVCAR-3	11.7	Colon ca. Colo-205	4.4
Ovarian ca. SK-OV-3	20.0	Colon ca. SW-48	4.3
Ovarian ca. OVCAR-4	8.7	Colon Pool	18.4
Ovarian ca. OVCAR-5	52.5	Small Intestine Pool	14.5
Ovarian ca. IGROV-1	28.1	Stomach Pool	10.4
Ovarian ca. OVCAR-8	15.7	Bone Marrow Pool	10.9
Ovary	22.4	Fetal Heart	3.6
Breast ca. MCF-7	39.2	Heart Pool	10.6
Breast ca. MDA-MB-231	54.3	Lymph Node Pool	15.2
Breast ca. BT 549	90.1	Fetal Skeletal Muscle	3.1
Breast ca. T47D	100.0	Skeletal Muscle Pool	3.6
Breast ca. MDA-N	11.6	Spleen Pool	11.5
Breast Pool	22.1	Thymus Pool	13.7
Trachea	23.7	CNS cancer (glio/astro) U87-MG	47.3
Lung	4.7	CNS cancer (glio/astro) U-118-MG	50.0
Fetal Lung	22.7	CNS cancer (neuro;met) SK-N-AS	9.0
Lung ca. NCI-N417	1.5	CNS cancer (astro) SF-539	33.9
Lung ca. LX-1	13.2	CNS cancer (astro) SNB-75	48.6
Lung ca. NCI-H146	7.8	CNS cancer (glio) SNB-19	24.1
Lung ca. SHP-77	10.5	CNS cancer (glio) SF-295	67.4
Lung ca. A549	17.8	Brain (Amygdala) Pool	11.7
Lung ca. NCI-H526	2.5	Brain (cerebellum)	13.6
Lung ca. NCI-H23	41.2	Brain (fetal)	19.8
Lung ca. NCI-H460	13.5	Brain (Hippocampus) Pool	12.7
Lung ca. HOP-62	21.8	Cerebral Cortex Pool	19.6
Lung ca. NCI-H522	6.8	Brain (Substantia nigra) Pool	13.6
Liver	6.6	Brain (Thalamus) Pool	16.5
Fetal Liver	19.3	Brain (whole)	18.8
Liver ca. HepG2	8.9	Spinal Cord Pool	13.3
Kidney Pool	31.0	Adrenal Gland	18.4
Fetal Kidney	7.5	Pituitary gland Pool	9.7
Renal ca. 786-0	42.3	Salivary Gland	13.3
Renal ca. A498	12.7	Thyroid (female)	19.3
Renal ca. ACHN	9.2	Pancreatic ca. CAPAN2	34.2
Renal ca. UO-31	26.8	Pancreas Pool	24.7

[0720]

TABLE FD
Panel 4.1D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4416,		Ag4416,
	Run		Run
Tissue Name	190281897	Tissue Name	190281897
Secondary Th1 act	12.9	HUVEC IL-1 beta	26.1
Secondary Th2 act	41.8	HUVEC IFN gamma	27.9
Secondary Tr1 act	33.4	HUVEC TNF alpha + IFN gamma	23.8
Secondary Th1 rest	32.5	HUVEC TNF alpha + IL4	35.1
Secondary Th2 rest	49.0	HUVEC IL-11	18.8
Secondary Tr1 rest	36.1	Lung Microvascular EC none	90.8
Primary Th1 act	21.3	Lung Microvascular EC TNFalpha +	85.3
		IL-1beta
Primary Th2 act	35.8	Microvascular Dermal EC none	40.1
Primary Tr1 act	24.5	Microvascular Dermal EC TNFalpha +	22.7
		IL-1beta
Primary Th1 rest	19.8	Bronchial epithelium TNFalpha +	25.3
		IL1beta
Primary Th2 rest	24.0	Small airway epithelium none	29.5
Primary Tr1 rest	35.1	Small airway epithelium TNFalpha +	42.3
		IL-1beta
CD45RA CD4 lymphocyte act	37.1	Coronery artery SMC rest	39.8
CD45RO CD4 lymphocyte act	37.6	Coronery artery SMC TNFalpha +	32.3
		IL-1beta
CD8 lymphocyte act	19.6	Astrocytes rest	39.0
Secondary CD8 lymphocyte rest	37.4	Astrocytes TNFalpha + IL-1beta	36.3
Secondary CD8 lymphocyte act	15.8	KU-812 (Basophil) rest	16.4
CD4 lymphocyte none	20.0	KU-812 (Basophil) PMA/ionomycin	23.5
2ry Th1/Th2/Tr1_anti-CD95	52.1	CCD1106 (Keratinocytes) none	18.9
CH11
LAK cells rest	44.8	CCD1106 (Keratinocytes) TNFalpha +	23.2
		IL-1beta
LAK cells IL-2	22.2	Liver cirrhosis	18.7
LAK cells IL-2 + IL-12	24.8	NCI-H292 none	36.3
LAK cells IL-2 + IFN gamma	44.8	NCI H-292 IL-4	45.7
LAK cells IL-2 + IL-18	50.0	NCI-H292 IL-9	52.9
LAK cells PMA/ionomycin	25.0	NCI-H292 IL-13	37.4
NK Cells IL-2 rest	47.0	NCI-H292 IFN gamma	32.3
Two Way MLR 3 day	42.3	HPAEC none	40.9
Two Way MLR 5 day	39.5	HPAEC TNF alpha + IL-1 beta	48.3
Two Way MLR 7 day	17.9	Lung fibroblast none	74.2
PBMC rest	21.2	Lung fibroblast TNF alpha + IL-1	54.3
		beta
PBMC PWM	16.6	Lung fibroblast IL-4	77.9
PBMC PHA-L	7.4	Lung fibroblast IL-9	100.0
Ramos (B cell) none	31.2	Lung fibroblast IL-13	56.3
Ramos (B cell) ionomycin	25.2	Lung fibroblast IFN gamma	84.7
B lymphocytes PWM	10.2	Dermal fibroblast CCD1070 rest	60.7
B lymphocytes CD40L and IL-4	31.6	Dermal fibroblast CCD1070 TNF	69.3
		alpha
EOL-1 dbcAMP	42.3	Dermal fibroblast CCD1070 IL-1	34.2
		beta
EOL-1 dbcAMP PMA/ionomycin	33.2	Dermal fibroblast IFN gamma	42.9
Dendritic cells none	79.0	Dermal fibroblast IL-4	55.5
Dendritic cells LPS	46.7	Dermal Fibroblasts rest	45.4
Dendritic cells anti-CD40	69.7	Neutrophils TNFa + LPS	11.8
Monocytes rest	49.3	Neutrophils rest	39.8
Monocytes LPS	30.4	Colon	15.4
Macrophages rest	79.0	Lung	31.6
Macrophages LPS	21.9	Thymus	21.0
HUVEC none	17.0	Kidney	27.9
HUVEC starved	28.3

[0721]

TABLE FE
general oncology screening panel_v_2.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4416,		Ag4416,
	Run		Run
Tissue Name	268665925	Tissue Name	268665925
Colon cancer 1	31.0	Bladder cancer NAT 2	0.4
Colon cancer NAT 1	10.9	Bladder cancer NAT 3	0.8
Colon cancer 2	21.5	Bladder cancer NAT 4	9.2
Colon cancer NAT 2	14.9	Prostate adenocarcinoma 1	77.4
Colon cancer 3	36.1	Prostate adenocarcinoma 2	4.2
Colon cancer NAT 3	19.9	Prostate adenocarcinoma 3	25.5
Colon malignant cancer 4	21.2	Prostate adenocarcinoma 4	7.0
Colon normal adjacent tissue 4	6.3	Prostate cancer NAT 5	5.3
Lung cancer 1	14.9	Prostate adenocarcinoma 6	17.3
Lung NAT 1	2.5	Prostate adenocarcinoma 7	12.7
Lung cancer 2	11.4	Prostate adenocarcinoma 8	3.5
Lung NAT 2	2.3	Prostate adenocarcinoma 9	57.4
Squamous cell carcinoma 3	25.5	Prostate cancer NAT 10	5.2
Lung NAT 3	3.1	Kidney cancer 1	25.2
metastatic melanoma 1	34.6	KidneyNAT 1	11.4
Melanoma 2	3.0	Kidney cancer 1	28.7
Melanoma 3	3.3	Kidney NAT 2	18.4
metastatic melanoma 4	76.8	Kidney cancer 3	18.3
metastatic melanoma 5	100.0	Kidney NAT 3	6.5
Bladder cancer 1	1.5	Kidney cancer 4	19.5
Bladder cancer NAT 1	0.0	Kidney NAT 4	11.3
Bladder cancer 2	6.9

[0722] CNS_neurodegeneration_v1.0 Summary: Ag4416 This panel confirms the expression of the CG110311-01 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. See Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.

[0723] General_screening_panel_v1.4 Summary: Ag4416 Highest expression of the CG110311-01 gene is detected in a breast cancer T47D cell line (CT=26). High levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreastic, gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0724] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0725] In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0726] Panel 4.1D Summary: Ag4416 Highest expression of the CG110311-01 gene is detected in IL-9 treated lung fibroblasts (CT=29). This gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0727] general oncology screening panel_v—2.4 Summary: Ag4416 Highest expression of the CG110311-01 gene is detected in metastatic melanoma (CT=27.7). High levels of expression of this gene is also seen in number of cancer samples derived from colon, lung, bladder, prostate, melanoma and kidney cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of these cancers.

[0728] G. CG110421-01 and CG110421-02: Peroxisomal Short-Chain Alcohol Dehydrogenase 2

[0729] Expression of gene CG110421-01 and CG110421-02 was assessed using the primer-probe sets Ag4441, Ag4428 and Ag5934, described in Tables GA, GB and GC. Results of the RTQ-PCR runs are shown in Tables GD, GE and GF.

TABLE GA
Probe Name Ag4441
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggcttcagtccttacaatgtca-3′	22	592	184
Probe	TET-5′-ctgaccaagaccctggccatagagct-3′-TAMRA	26	634	185
Reverse	5′-gcagttcaccctaatgttcct-3′	21	667	186

[0730]

TABLE GB
Probe Name Ag4428
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-atcactggggaaacagtggt-3′	20	847	187
Probe	TET-5′-ctctgaggaccgggagacagccc-3′-TAMRA	23	892	188
Reverse	5′-gagctagagcccaactctgg-3′	20	920	189

[0731]

TABLE GC
Probe Name Ag5934
Primers	Sequences	Length	Start Position	SEQ ID No
Forward	5′-tttggaagcctaatggatgt-3′	20	427	190
Probe	TET-5′-agccctgatgacaaaggcagt-3′-TAMRA	21	495	191
Reverse	5′-gagatggactgaaggctgcta-3′	21	569	192

[0732]

TABLE GD
General_screening_panel_v1.4
		Rel.	Rel.
		Exp. (%)	Exp. (%)
		Ag4428,	Ag4441,
		Run	Run
	Tissue Name	222645454	220005642
	Adipose	3.8	4.1
	Melanoma* Hs688(A).T	28.7	28.1
	Melanoma* Hs688(B).T	23.0	26.2
	Melanoma* M14	16.5	21.6
	Melanoma* LOXIMVI	14.8	15.2
	Melanoma* SK-MEL-5	32.8	50.0
	Squamous cell carcinoma	12.5	11.3
	SCC-4
	Testis Pool	15.2	4.9
	Prostate ca.*	22.8	32.8
	(bone met)
	PC-3
	Prostate Pool	8.9	8.1
	Placenta	3.2	3.0
	Uterus Pool	3.7	4.5
	Ovarian ca. OVCAR-3	23.8	26.4
	Ovarian ca. SK-OV-3	25.7	27.9
	Ovarian ca. OVCAR-4	12.2	12.7
	Ovarian ca. OVCAR-5	57.4	40.9
	Ovarian ca. IGROV-1	16.6	18.9
	Ovarian ca. OVCAR-8	18.0	20.4
	Ovary	14.7	13.9
	Breast ca. MCF-7	61.6	95.3
	Breast ca. MDA-MB-231	12.8	14.6
	Breast ca. BT 549	18.6	20.0
	Breast ca. T47D	100.0	100.0
	Breast ca. MDA-N	9.0	12.9
	Breast Pool	12.7	10.5
	Trachea	7.4	7.0
	Lung	8.9	4.7
	Fetal Lung	15.3	13.8
	Lung ca. NCI-N417	8.3	6.8
	Lung ca. LX-1	22.8	25.7
	Lung ca. NCI-H146	7.3	3.8
	Lung ca. SHP-77	19.2	11.4
	Lung ca. A549	40.6	31.6
	Lung ca. NCI-H526	7.0	3.6
	Lung ca. NCI-H23	37.9	44.4
	Lung ca. NCI-H460	17.0	19.6
	Lung ca. HOP-62	13.5	11.9
	Lung ca. NCI-H522	24.1	28.7
	Liver	7.5	12.9
	Fetal Liver	19.6	20.7
	Liver ca. HepG2	7.0	8.0
	Kidney Pool	19.6	11.4
	Fetal Kidney	10.7	11.7
	Renal ca. 786-0	14.0	24.1
	Renal ca. A498	9.4	6.3
	Renal ca. ACHN	11.1	9.0
	Renal ca. UO-31	15.8	19.3
	Renal ca. TK-10	11.1	14.1
	Bladder	12.5	14.0
	Gastric ca.	13.4	17.2
	(liver met.) NCI-N87
	Gastric ca. KATO III	95.9	31.6
	Colon ca. SW-948	13.7	19.9
	Colon ca. SW480	30.1	36.3
	Colon ca.* (SW480 met)	22.7	24.3
	SW620
	Colon ca. HT29	11.0	11.0
	Colon ca. HCT-116	31.6	25.2
	Colon ca. CaCo-2	6.4	10.2
	Colon cancer tissue	16.5	20.4
	Colon ca. SW1116	7.7	6.7
	Colon ca. Colo-205	21.2	9.3
	Colon ca. SW-48	11.4	6.6
	Colon Pool	12.8	11.0
	Small Intestine Pool	7.6	7.7
	Stomach Pool	6.7	7.5
	Bone Marrow Pool	5.1	3.0
	Fetal Heart	9.2	9.3
	Heart Pool	8.8	6.6
	Lymph Node Pool	13.5	12.9
	Fetal Skeletal Muscle	2.7	2.8
	Skeletal Muscle Pool	17.3	9.2
	Spleen Pool	7.7	9.1
	Thymus Pool	9.7	9.3
	CNS cancer (glio/astro)	25.2	44.1
	U87-MG
	CNS cancer (glio/astro)	17.4	22.2
	U-118-MG
	CNS cancer (neuro; met)	8.7	9.2
	SK-N-AS
	CNS cancer (astro)	11.7	10.4
	SF-539
	CNS cancer (astro)	35.1	40.1
	SNB-75
	CNS cancer (glio)	12.9	18.4
	SNB-19
	CNS cancer (glio)	18.8	19.6
	SF-295
	Brain (Amygdala) Pool	6.5	4.5
	Brain (cerebellum)	8.4	3.6
	Brain (fetal)	3.5	2.1
	Brain (Hippocampus)	4.6	4.3
	Pool
	Cerebral Cortex Pool	6.3	5.3
	Brain (Substantia nigra)	3.7	4.2
	Pool
	Brain (Thalamus) Pool	9.6	6.2
	Brain (whole)	5.7	3.1
	Spinal Cord Pool	7.8	8.2
	Adrenal Gland	15.9	13.9
	Pituitary gland Pool	2.4	2.2
	Salivary Gland	6.7	8.2
	Thyroid (female)	7.9	7.3
	Pancreatic ca. CAPAN2	15.8	23.3
	Pancreas Pool	13.8	12.0

[0733]

TABLE GE
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5934,		Ag5934,
	Run		Run
Tissue Name	247834838	Tissue Name	248734838
Adipose	0.0	Renal ca. TK-10	11.3
Melanoma* Hs688(A).T	11.1	Bladder	21.3
Melanoma* Hs688(B).T	9.4	Gastric ca. (liver met.) NCI-N87	39.2
Melanoma* M14	12.3	Gastric ca. KATO III	1.4
Melanoma* LOXIMVI	13.4	Colon ca. SW-948	66.0
Melanoma* SK-MEL-5	33.9	Colon ca. SW480	51.4
Squamous cell carcinoma SCC-4	7.2	Colon ca.* (SW480 met) SW620	48.0
Testis Pool	61.1	Colon ca. HT29	28.5
Prostate ca.* (bone met) PC-3	13.8	Colon ca. HCT-116	54.0
Prostate Pool	5.9	Colon ca. CaCo-2	10.4
Placenta	1.4	Colon cancer tissue	16.4
Uterus Pool	0.0	Colon ca. SW1116	19.6
Ovarian ca. OVCAR-3	16.5	Colon ca. Colo-205	100.0
Ovarian ca. SK-OV-3	7.3	Colon ca. SW-48	30.8
Ovarian ca. OVCAR-4	2.7	Colon Pool	5.3
Ovarian ca. OVCAR-5	44.8	Small Intestine Pool	2.3
Ovarian ca. IGROV-1	9.5	Stomach Pool	3.5
Ovarian ca. OVCAR-8	9.9	Bone Marrow Pool	0.0
Ovary	8.4	Fetal Heart	1.2
Breast ca. MCF-7	28.7	Heart Pool	5.4
Breast ca. MDA-MB-231	9.4	Lymph Node Pool	5.2
Breast ca. BT 549	3.3	Fetal Skeletal Muscle	0.0
Breast ca. T47D	36.3	Skeletal Muscle Pool	62.4
Breast ca. MDA-N	5.6	Spleen Pool	2.8
Breast Pool	4.6	Thymus Pool	8.4
Trachea	4.8	CNS cancer (glio/astro) U87-MG	10.6
Lung	0.9	CNS cancer (glio/astro) U-118-MG	6.5
Fetal Lung	5.3	CNS cancer (neuro;met) SK-N-AS	7.7
Lung ca. NCI-N417	6.7	CNS cancer (astro) SF-539	15.2
Lung ca. LX-1	59.0	CNS cancer (astro) SNB-75	26.2
Lung ca. NCI-H146	4.5	CNS cancer (glio) SNB-19	11.2
Lung ca. SHP-77	42.6	CNS cancer (glio) SF-295	4.0
Lung ca. A549	38.4	Brain (Amygdala) Pool	2.7
Lung ca. NCI-H526	18.7	Brain (cerebellum)	6.2
Lung ca. NCI-H23	57.4	Brain (fetal)	0.0
Lung ca. NCI-H460	26.1	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	5.6	Cerebral Cortex Pool	1.2
Lung ca. NCI-H522	8.7	Brain (Substantia nigra) Pool	5.6
Liver	21.2	Brain (Thalamus) Pool	4.4
Fetal Liver	25.0	Brain (whole)	2.1
Liver ca. HepG2	5.0	Spinal Cord Pool	5.3
Kidney Pool	3.8	Adrenal Gland	9.8
Fetal Kidney	2.9	Pituitary gland Pool	0.0
Renal ca. 786-0	29.1	Salivary Gland	12.4
Renal ca. A498	15.4	Thyroid (female)	3.0
Renal ca. ACHN	3.9	Pancreatic ca. CAPAN2	12.1
Renal ca. UO-31	29.9	Pancreas Pool	2.3

[0734]

TABLE GF
Panel 5 Islet
	Rel.		Rel.
	Exp. (%)	Exp. (%)
	Ag4428,		Ag4428,
	Run		Run
Tissue Name	242449344	Tissue Name	242449344
97457_Patient-02go_adipose	33.4	94709_Donor 2 AM - A_adipose	38.4
97476_Patient-07sk_skeletal	21.8	94710_Donor 2 AM - B_adipose	33.7
muscle
97477_Patient-07ut_uterus	24.1	94711_Donor 2 AM - C_adipose	27.0
97478_Patient-07pl_placenta	6.6	94712_Donor 2 AD - A_adipose	35.8
99167_Bayer Patient 1	100.0	94713_Donor 2 AD - B_adipose	35.4
97482_Patient-08ut_uterus	10.2	94714_Donor 2 AD - C_adipose	26.1
97483_Patient-08pl_placenta	4.9	94742_Donor 3 U - A_Mesenchymal	17.6
		Stem Cells
97486_Patient-09sk_skeletal	7.6	94743_Donor 3 U - B_Mesenchymal	33.0
muscle		Stem Cells
97487_Patient-09ut_uterus	25.5	94730_Donor 3 AM - A_adipose	36.9
97488_Patient-09pl_placenta	10.2	94731_Donor 3 AM - B_adipose	20.7
97492_Patient-10ut_uterus	21.2	94732_Donor 3 AM - C_adipose	26.2
97493_Patient-10pl_placenta	21.3	94733_Donor 3 AD - A_adipose	70.2
97495_Patient-11go_adipose	12.6	94734_Donor 3 AD - B_adipose	27.7
97496_Patient-11sk_skeletal	4.6	94735_Donor 3 AD - C_adipose	37.4
muscle
97497_Patient-11ut_uterus	10.5	77138_Liver_HepG2untreated	41.2
97498_Patient-11pl_placenta	8.4	73556_Heart_Cardiac stomal cells	14.4
		(primary)
97500_Patient-12go_adipose	51.1	81735_Small Intestine	68.8
97501_Patient-12sk_skeletal	86.5	72409_Kidney_Proximal Convoluted	13.0
muscle		Tubule
97502_Patient-12ut_uterus	33.2	82685_Small intestine_Duodenum	28.1
97503_Patient-12pl_placenta	13.7	90650_Adrenal_Adrenocortical adenoma	37.1
94721_Donor 2 U -	25.0	72410_Kidney_HRCE	77.4
A_Mesenchymal Stem Cells
94722_Donor 2 U -	29.5	72411_Kidney_HRE	26.2
B_Mesenchymal Stem Cells
94723_Donor 2 U -	41.5	73139_Uterus_Uterine smooth muscle	22.7
C_Mesenchymal Stem Cells		cells

[0735] General_screening_panel_v1.4 Summary: Ag4428/Ag4441 Two experiments with different probe and primer sets are in excellent agreement with highest expression of the CG110421-01 gene in breast cancer T47D cell line (CTs=24.5-26). High levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0736] Among tissues with metabolic or endocrine function, this gene is expressed at moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0737] In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0738] General_screening_panel_v1.5 Summary: Ag5934 Highest expression of this gene is seen in a colon cancer cell line (CT=32.3). This gene is widely expressed in the cancer cell lines on this panel, with low but significant levels of expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0739] Among tissues with metabolic function, this gene is expressed at low but significant levels fetal skeletal muscle and adult and fetal liver. This expression suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0740] Panel 5 Islet Summary: Ag4428 Highest expression of this gene in human islet cells (Bayer patient 1) (CT=29.8). This gene codes for peroxisomal short-cahin alcohol dehydrogenase. Thus, the expression of this gene in human islet cells suggests that peroxisomal oxidation pathways may be important in beta cell physiology. Therefore, pharmacologic modulation of this enzyme, or other enzymes in the same pathway, may be useful for enhancing insulin secretion in Type 2 diabetes.

[0741] In addition, moderate levels of expression of this gene is also seen in most of the tissues with metabolic/endocrine function examined including adipose, placenta, uterus, skeletal muscle and small intestine. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0742] H. CG110531-01 and CG110531-02: Proteasome Subunit Alpha Type 7 (EC 3.4.99.46) (Proteasome Subunit Alpha 4)

[0743] Expression of gene CG110531-01 and CG110531-02 was assessed using the primer-probe set Ag4421, described in Table HA. Results of the RTQ-PCR runs are shown in Table HB. Please note that CG110531-02 represents a full-length physical clone of the CG110531-01 gene, validating the prediction of the gene sequence.

TABLE HA
Probe Name Ag4421
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gatgttttgagaatgccagatc-3′	22	931	193
Probe	TET-5′-tgtggctgtcttcattctattacatagtca-3′-TAMRA	30	953	194
Reverse	5′-actgaaatcccctttcaaagaa-3′	22	1005	195

[0744]

TABLE HB
Panel 4.1D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4421,		Ag4421,
	Run		Run
Tissue Name	190282082	Tissue Name	190282082
Secondary Th1 act	0.0	HUVEC IL-1beta	0.0
Secondary Th2 act	1.7	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN gamma	0.0
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC none	0.0
Primary Th1 act	0.0	Lung Microvascular EC TNFalpha +	0.0
		IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC none	0.0
Primary Tr1 act	0.0	Microsvasular Dermal EC TNFalpha +	0.0
		IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium TNFalpha +	0.0
		IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	0.0
Primary Tr1 rest	0.0	Small airway epithelium TNFalpha +	0.0
		IL-1beta
CD45RA CD4 lymphocyte act	1.6	Coronery artery SMC rest	0.0
CD45RO CD4 lymphocyte act	3.0	Coronery artery SMC TNFalpha +	0.0
		IL-1beta
CD8 lymphocyte act	2.5	Astrocytes rest	0.0
Secondary CD8 lymphocyte rest	0.0	Astrocytes TNFalpha + IL-1beta	0.0
Secondary CD8 lymphocyte act	0.0	KU-812 (Basophil) rest	0.0
CD4 lymphocyte none	0.0	KU-812 (Basophil) PMA/ionomycin	0.0
2ry Th1/Th2/Tr1_anti-CD95	0.0	CCD1106 (Keratinocytes) none	0.0
CH11
LAK cells rest	0.0	CCD1106 (Keratinocytes) TNFalpha +	0.0
		IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IFN gamma	0.0	NCI-H292 IL-4	0.0
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells PMA/ionomycin	0.0	NCI-H292 IL-13	0.0
NK Cells IL-2 rest	2.2	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	2.1	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1 beta	0.0
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	0.0	Lung fibroblast TNF alpha + IL-1	0.0
		beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	4.3	Lung fibroblast IL-9	0.0
Ramos (B cell) none	30.6	Lung fibroblast IL-13	0.0
Ramos (B cell) ionomycin	24.7	Lung fibroblast IFN gamma	0.0
B lymphocytes PWM	1.6	Dermal fibroblast CCD1070 rest	0.0
B lymphocytes CD40L and IL-4	0.0	Dermal fibroblast CCD1070 TNF	0.0
		alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070 IL-1	0.0
		beta
EOL-1 dbcAMP PMA/ionomycin	0.0	Dermal fibroblast IFN gamma	0.0
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.0
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	0.0
Macrophages rest	0.0	Lung	4.3
Macrophages LPS	0.0	Thymus	16.8
HUVEC none	0.0	Kidney	100.0
HUVEC starved	0.0

[0745] CNS_neurodegeneration_v1.0 Summary: Ag4421 Expression of the CG110531-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0746] General_screening_panel_v1.4 Summary: Ag4421 Expression of the CG110531-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0747] Panel 4.1D Summary: Ag4421 Low levels of expression of the CG110531-01 gene is restricted to kidney. Thus, expression of this gene could be used to differentiate the kidney derived sample from other samples on this panel and as a marker of kidney tissue. In addition, therapeutic targeting of the expression or function of this gene may modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.

[0748] general oncology screening panel_v—2.4 Summary: Ag4421 Expression of the CG110531-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0749] I. CG111231-01: Galactosyltransferase

[0750] Expression of gene CG111231-01 was assessed using the primer-probe set Ag4437, described in Table IA. Results of the RTQ-PCR runs are shown in Tables IB, IC, ID and IE.

TABLE IA
Probe Name Ag4437
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ccctagcatggaaggaaatt-3′	20	989	196
Probe	TET-5′-cactgtttgagacatcctatgagctca-3′-TAMRA	27	1028	197
Reverse	5′-cgtcagaagtttgcaggaaa-3′	20	1055	198

[0751]

TABLE IB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4437,		Ag4437,
	Run		Run
Tissue Name	224534931	Tissue Name	224534931
AD 1 Hippo	2.6	Control (Path) 3 Temporal Ctx	6.9
AD 2 Hippo	28.1	Control (Path) 4 Temporal Ctx	20.4
AD 3 Hippo	6.9	AD 1 Occipital Ctx	10.8
AD 4 Hippo	14.3	AD 2 Occipital Ctx (Missing)	0.0
AD 5 Hippo	61.1	AD 3 Occipital Ctx	13.1
AD 6 Hippo	45.1	AD 4 Occipital Ctx	11.3
Control 2 Hippo	31.4	AD 5 Occipital Ctx	33.7
Control 4 Hippo	24.5	AD 6 Occipital Ctx	26.1
Control (Path) 3 Hippo	7.1	Control 1 Occipital Ctx	7.5
AD 1 Temporal Ctx	10.0	Control 2 Occipital Ctx	43.8
AD 2 Temporal Ctx	22.5	Control 3 Occipital Ctx	19.8
AD 3 Temporal Ctx	4.5	Control 4 Occipital Ctx	20.3
AD 4 Temporal Ctx	11.6	Control (Path) 1 Occipital Ctx	65.1
AD 5 Inf Temporal Ctx	100.0	Control (Path) 2 Occipital Ctx	6.2
AD 5 Sup Temporal Ctx	74.2	Control (Path) 3 Occipital Ctx	1.8
AD 6 Inf Temporal Ctx	57.0	Control (Path) 4 Occipital Ctx	16.6
AD 6 Sup Temporal Ctx	42.0	Control 1 Parietal Ctx	10.9
Control 1 Temporal Ctx	10.9	Control 2 Parietal Ctx	44.4
Control 2 Temporal Ctx	29.9	Control 3 Parietal Ctx	22.7
Control 3 Temporal Ctx	10.0	Control (Path) 1 Parietal Ctx	74.7
Control 3 Temporal Ctx	7.2	Control (Path) 2 Parietal Ctx	32.1
Control (Path) 1 Temporal Ctx	41.5	Control (Path) 3 Parietal Ctx	17.2
Control (Path) 2 Temporal Ctx	30.8	Control (Path) 4 Parietal Ctx	63.7

[0752]

TABLE IC
General_screening_panel_v1.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4437,		Ag4437,
	Run		Run
Tissue Name	219979318	Tissue Name	219979318
Adipose	5.5	Renal ca. TK-10	69.3
Melanoma* Hs688(A).T	6.1	Bladder	7.1
Melanoma* Hs688(B).T	6.7	Gastric ca. (liver met.) NCI-N87	58.6
Melanoma* M14	13.1	Gastric ca. KATO III	79.6
Melanoma* LOXIMVI	25.2	Colon ca. SW-948	12.0
Melanoma* SK-MEL-5	3.7	Colon ca. SW480	62.4
Squamous cell carcinoma SCC-	24.1	Colon ca.* (SW480 met) SW620	40.1
4
Testis Pool	9.5	Colon ca. HT29	10.3
Prostate ca.* (bone met) PC-3	34.2	Colon ca. HCT-116	40.1
Prostate Pool	4.8	Colon ca. CaCo-2	30.1
Placenta	4.0	Colon cancer tissue	9.0
Uterus Pool	0.8	Colon ca. SW1116	4.9
Ovarian ca. OVCAR-3	60.3	Colon ca. Colo-205	5.3
Ovarian ca. SK-OV-3	41.2	Colon ca. SW-48	7.4
Ovarian ca. OVCAR-4	1.2	Colon Pool	6.7
Ovarian ca. OVCAR-5	48.3	Small Intestine Pool	11.0
Ovarian ca. IGROV-1	29.1	Stomach Pool	3.4
Ovarian ca. OVCAR-8	12.7	Bone Marrow Pool	1.7
Ovary	6.1	Fetal Heart	7.4
Breast ca. MCF-7	32.8	Heart Pool	3.8
Breast ca. MDA-MB-231	75.3	Lymph Node Pool	7.3
Breast ca. BT 549	47.0	Fetal Skeletal Muscle	5.1
Breast ca. T47D	100.0	Skeletal Muscle Pool	8.2
Breast ca. MDA-N	19.5	Spleen Pool	7.5
Breast Pool	10.9	Thymus Pool	8.5
Trachea	13.5	CNS cancer (glio/astro) U87-MG	68.3
Lung	6.3	CNS cancer (glio/astro) U-118-	54.0
		MG
Fetal Lung	15.4	CNS cancer (neuro;met) SK-N-AS	49.7
Lung ca. NCI-N417	7.3	CNS cancer (astro) SF-539	13.8
Lung ca. LX-1	34.9	CNS cancer (astro) SNB-75	90.8
Lung ca. NCI-H146	2.8	CNS cancer (glio) SNB-19	27.7
Lung ca. SHP-77	31.2	CNS cancer (glio) SF-295	35.4
Lung ca. A549	28.5	Brain (Amygdala) Pool	3.2
Lung ca. NCI-H526	6.6	Brain (cerebellum)	4.2
Lung ca. NCI-H23	47.3	Brain (fetal)	8.6
Lung ca. NCI-H460	40.3	Brain (Hippocampus) Pool	5.5
Lung ca. HOP-62	23.7	Cerebral Cortex Pool	3.7
Lung ca. NCI-H522	50.7	Brain (Substantia nigra) Pool	6.2
Liver	1.5	Brain (Thalamus) Pool	7.1
Fetal Liver	9.0	Brain (whole)	6.1
Liver ca. HepG2	11.2	Spinal Cord Pool	9.3
Kidney Pool	13.1	Adrenal Gland	8.6
Fetal Kidney	18.0	Pituitary gland Pool	6.3
Renal ca. 786-0	38.2	Salivary Gland	5.5
Renal ca. A498	7.2	Thyroid (female)	8.0
Renal ca. ACHN	15.4	Pancreatic ca. CAPAN2	26.2
Renal ca. UO-31	9.7	Pancreas Pool	12.7

[0753]

TABLE ID
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4437, Run		Ag4347, Run
Tissue Name	190820032	Tissue Name	190820032
Secondary Th1 act	55.5	HUVEC IL-1beta	10.7
Secondary Th2 act	68.3	HUVEC IFN gamma	25.0
Secondary Tr1 act	76.8	HUVEC TNF alpha + IFN gamma	14.7
Secondary Th1 rest	23.2	HUVEC TNF alpha + IL4	17.2
Secondary Th2 rest	38.2	HUVEC IL-11	15.0
Secondary Tr1 rest	20.4	Lung Microvascular EC none	18.3
Primary Th1 act	42.0	Lung Microvascular EC	26.2
		TNFalpha + IL-1beta
Primary Th2 act	57.8	Microvascular Dermal EC none	11.0
Primary Tr1 act	40.9	Microsvasular Dermal EC	6.5
		TNFalpha + IL-1beta
Primary Th1 rest	16.5	Bronchial epithelium TNFalpha +	33.2
Primary Th2 rest	5.9	Small airway epithelium none	8.7
Primary Tr1 rest	25.0	Small airway epithelium	34.2
		TNFalpha + IL-1beta
CD45RA CD4 lymphocyte act	50.0	Coronery artery SMC rest	16.2
CD45RO CD4 lymphocyte act	82.9	Coronery artery SMC TNFalpha +	22.4
		IL-1beta
CD 8 lymphocyte act	73.7	Astrocytes rest	30.1
Secondary CD8 lymphocyte	57.0	Astrocytes TNFalpha + IL-1beta	20.0
rest
Secondary CD8 lymphocyte act	37.9	KU-812 (Basophil) rest	32.8
CD4 lymphocyte none	22.7	KU-812 (Basophil)	40.9
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	57.0	CCD1106 (Keratinocytes) none	100.0
CH11
LAK cells rest	52.9	CCD1106 (Keratinocytes)	32.1
		TNFalpha + IL-1beta
LAK cells IL-2	85.3	Liver cirrhosis	10.7
LAK cells IL-2 + IL-12	28.7	NCI-H292 none	39.5
LAK cells IL-2 + IFN gamma	30.1	NCI-H292 IL-4	55.5
LAK cells IL-2 + IL-18	55.1	NCI-H292 IL-9	44.8
LAK cells PMA/ionomycin	9.5	NCI-H292 IL-13	42.6
NK Cells IL-2 rest	84.1	NCI-H292 IFN gamma	47.0
Two Way MLR 3 day	44.1	HPAEC none	10.7
Two Way MLR 5 day	22.4	HPAEC TNF alpha + IL-1 beta	28.3
Two Way MLR 7 day	18.3	Lung fibroblast none	50.0
PBMC rest	10.0	Lung fibroblast TNF alpha + IL-1	22.1
		beta
PBMC PWM	24.7	Lung fibroblast IL-4	34.9
PBMC PHA-L	43.5	Lung fibroblast IL-9	41.8
Ramos (B cell) none	59.9	Lung fibroblast IL-13	35.4
Ramos (B cell) ionomycin	85.9	Lung fibroblast IFN gamma	20.9
B lymphocytes PWM	47.3	Dermal fibroblast CCD1070 rest	32.3
B lymphocytes CD40L and IL-	62.9	Dermal fibroblast CCD1070 TNF	42.3
4		alpha
EOL-1 dbcAMP	10.3	Dermal fibroblast CCD1070 IL-1	18.0
		beta
EOL-1 dbcAMP	10.4	Dermal fibroblast IFN gamma	17.0
PMA/ionomycin
Dendritic cells none	21.6	Dermal fibroblast IL-4	27.7
Dendritic cells LPS	25.3	Dermal Fibroblasts rest	22.4
Dendritic cells anti-CD40	14.1	Neutrophils TNFa + LPS	0.0
Monocytes rest	15.8	Neutrophils rest	1.2
Monocytes LPS	23.7	Colon	0.8
Macrophages rest	18.7	Lung	18.3
Macrophages LPS	11.5	Thymus	29.3
HUVEC none	8.8	Kidney	62.9
HUVEC starved	17.8

[0754]

TABLE IE
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4437, Run		Ag4437, Run
Tissue Name	268672114	Tissue Name	268672114
Colon cancer 1	11.7	Bladder cancer NAT 2	0.4
Colon cancer NAT 1	4.7	Bladder cancer NAT 3	1.7
Colon cancer 2	20.9	Bladder cancer NAT 4	1.2
Colon cancer NAT 2	8.5	Prostate adenocarcinoma 1	41.2
Colon cancer 3	26.1	Prostate adenocarcinoma 2	1.8
Colon cancer NAT 3	21.2	Prostate adenocarcinoma 3	8.2
Colon malignant cancer 4	45.1	Prostate adenocarcinoma 4	7.3
Colon normal adjacent tissue 4	6.4	Prostate cancer NAT 5	8.1
Lung cancer 1	27.0	Prostate adenocarcinoma 6	3.3
Lung NAT 1	0.3	Prostate adenocarcinoma 7	3.3
Lung cancer 2	54.3	Prostate adenocarcinoma 8	0.8
Lung NAT 2	1.7	Prostate adenocarcinoma 9	10.1
Squamous cell carcinoma 3	17.3	Prostate cancer NAT 10	1.7
Lung NAT 3	2.1	Kidney cancer 1	16.3
metastatic melanoma 1	19.5	KidneyNAT 1	9.2
Melanoma 2	6.6	Kidney cancer 2	100.0
Melanoma 3	3.9	Kidney NAT 2	26.4
metastatic melanoma 4	31.0	Kidney cancer 3	10.6
metastatic melanoma 5	27.9	Kidney NAT 3	12.2
Bladder cancer 1	2.3	Kidney cancer 4	16.6
Bladder cancer NAT 1	0.0	Kidney NAT 4	11.0
Bladder cancer 2	5.6

[0755] CNS_neurodegeneration_v1.0 Summary: Ag4437 This expression profile confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.

[0756] General_screening_panel_v1.4 Summary: Ag4437 Highest expression of this gene is seen in a breast cancer cell line (CT=28.3). This gene is widely expressed in this panel, with higher levels of expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0757] Among tissues with metabolic function, this gene is expressed at low but significant levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0758] This gene is also expressed at low but significant levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0759] Panel 4.1D Summary: Ag4437 This gene is expressed at moderate to low levels in a wide range of cell types of significance in the immune response in health and disease, with highest expression in ketatinocytes (CYT=30.8). In addition, expression is detected in members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0760] general oncology screening panel_v—2.4 Summary: Ag4437 This gene is widely expressed in this panel, with highest expression in kidney cancer (CT=29.9). In addition, this gene is more highly expressed in lung, colon and kidney cancer than in the corresponding normal adjacent tissue. Thus, expression of this gene could be used as a marker of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of lung, colon and kidney cancer.

[0761] J. CG111293-02: Protoporphyrinogen Oxidase.

[0762] Expression of gene CG111293-02 was assessed using the primer-probe set Ag6779, described in Table JA. Results of the RTQ-PCR runs are shown in Table JB. Please note that CG111293-02 is a full length physical clone.

TABLE JA
Probe Name Ag6779
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gaggccctaatggtgctatc-3′	20	417	199
Probe	TET-5′-ctaattccccgaggtccaagctcaaa-3′-TAMRA	26	437	200
Reverse	5′-cccttagagataccaggagcaa-3′	22	491	201

[0763]

TABLE JB
General_screening_panel_v1.6
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6779,		Ag6779,
	Run		Run
Tissue Name	277640750	Tissue Name	277640750
Adipose	0.0	Renal ca. TK-10	6.1
Melanoma* Hs688(A).T	4.7	Bladder	4.0
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.) NCI-N87	4.4
Melanoma* M14	1.7	Gastric ca. KATO III	1.4
Melanoma* LOXIMVI	5.3	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	20.4
Squamous cell carcinoma SCC-4	0.0	Colon ca.* (SW480 met) SW620	12.4
Testis Pool	0.0	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	26.4	Colon ca. HCT-116	100.0
Prostate Pool	0.0	Colon ca. CaCo-2	27.7
Placenta	1.9	Colon cancer tissue	0.0
Uterus Pool	0.0	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	1.7	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	6.7	Colon ca. SW-48	1.4
Ovarian ca. OVCAR-4	14.2	Colon Pool	6.4
Ovarian ca. OVCAR-5	32.5	Small Intestine Pool	1.4
Ovarian ca. IGROV-1	3.3	Stomach Pool	1.7
Ovarian ca. OVCAR-8	1.3	Bone Marrow Pool	1.6
Ovary	1.5	Fetal Heart	1.1
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-MB-231	9.3	Lymph Node Pool	3.4
Breast ca. BT 549	7.4	Fetal Skeletal Muscle	0.0
Breast ca. T47D	2.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	6.6	Spleen Pool	4.3
Breast Pool	3.2	Thymus Pool	1.6
Trachea	1.5	CNS cancer (glio/astro) U87-MG	10.7
Lung	0.0	CNS cancer (glio/astro) U-118-MG	6.4
Fetal Lung	3.0	CNS cancer (neuro;met) SK-N-AS	18.2
Lung ca. NCI-N417	2.5	CNS cancer (astro) SF-539	1.5
Lung ca. LX-1	12.1	CNS cancer (astro) SNB-75	9.2
Lung ca. NCI-H146	6.2	CNS cancer (glio) SNB-19	2.7
Lung ca. SHP-77	39.5	CNS cancer (glio) SF-295	3.5
Lung ca. A549	19.9	Brain (Amygdala) Pool	6.3
Lung ca. NCI-H526	23.3	Brain (cerebellum)	6.7
Lung ca. NCI-H23	12.9	Brain (fetal)	3.5
Lung ca. NCI-H460	2.6	Brain (Hippocampus) Pool	5.3
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	7.3
Lung ca. NCI-H522	24.7	Brain (Substantia nigra) Pool	11.3
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	39.0	Brain (whole)	5.6
Liver ca. HepG2	4.6	Spinal Cord Pool	1.6
Kidney Pool	5.5	Adrenal Gland	5.5
Fetal Kidney	8.8	Pituitary gland Pool	0.0
Renal ca. 786-0	31.9	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	17.6	Pancreatic ca. CAPAN2	10.7
Renal ca. UO-31	3.8	Pancreas Pool	10.7

[0764] CNS_neurodegeneration_v1.0 Summary: Ag6779 Expression of the CG111293-02 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0765] General_screening_panel_v1.6 Summary: Ag6779 Highest expression of the CG111293-02 gene is detected in a colon cancer HCT-116 cell line (CT=33.4). Thus, expression of this gene may be used to differentiate this sample from other samples used in this panel. In addition, low levels of expression of this gene is also seen in a lung cancer SHP-77 cell line. Therefore, expression of this gene may be used as marker for detection of colon and lung cancer. Furthermore, therapeutic modulation of this gene through the use of small molecule drug may be useful in the treatment of lung and colon cancer.

[0766] Low levels of expression of this gene is also seen in fetal liver. Interestingly, this gene is expressed at much higher levels in fetal (CT=34.7) when compared to adult liver (CT=40). This observation suggests that expression of this gene can be used to distinguish fetal from adult liver. In addition, the relative overexpression of this gene in fetal liver suggests that the protein product may enhance liver growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of liver related diseases.

[0767] Panel 4.1D Summary: Ag6779 Expression of the CG111293-02 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0768] K. CG111293-03: Protoporphyrinogen Oxidase

[0769] Expression of gene CG111293-03 was assessed using the primer-probe set Ag6797, described in Table KA.

TABLE KA
Probe Name Ag6797
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-accttgctcctggtgatgct-3′	20	488	202
Probe	TET-5′-cacagccactagcctctagtgtctgtaaccaggaa-3′-TAMRA	35	514	203
Reverse	5′-ctgttgaaacagctcctgagataag-3′	25	550	204

[0770]

TABLE KB
General_screening_panel_v1.6
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag6797, Run		Ag6797, Run
Tissue Name	278017529	Tissue Name	278017529
Adipose	0.0	Renal ca. TK-10	0.0
Melanoma* Hs688(A).T	0.0	Bladder	0.0
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.) NCI-N87	0.0
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	2.2
Squamous cell carcinoma SCC-	0.0	Colon ca.* (SW480 met) SW620	0.0
4
Testis Pool	0.0	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	15.9	Colon ca. HCT-116	0.0
Prostate Pool	1.8	Colon ca. CaCo-2	0.0
Placenta	0.0	Colon cancer tissue	0.0
Uterus Pool	2.9	Colon ca. SW1116
Ovarian ca. OVCAR-3	2.8	Colon Ca. Colo-205	0.0
Ovarian ca. SK-OV-3	1.8	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	1.8	Colon Pool	3.2
Ovarian ca. OVCAR-5	2.7	Small Intestine Pool	7.2
Ovarian ca. IGROV-1	2.6	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	2.6	Fetal Heart	2.9
Breast ca. MCF-7	0.0	Heart Pool	2.1
Breast ca. MDA-MB-231	7.3	Lymph Node Pool	4.3
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	0.0
Breast Pool	7.3	Thymus Pool	5.0
Trachea	0.0	CNS cancer (glio/astro) U87-MG	6.8
Lung	0.0	CNS cancer (glio/astro) U-118-	0.0
		MG
Fetal Lung	27.5	CNS cancer (neuro;met) SK-N-AS	2.1
Lung ca. NCI-N417	3.7	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-75	1.8
Lung ca. NCI-H146	2.8	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	3.9	CNS cancer (glio) SF-295	4.2
Lung ca. A549	0.0	Brain (Amygdala) Pool	13.5
Lung ca. NCI-H526	1.8	Brain (cerebellum)	41.2
Lung ca. NCI-H23	3.6	Brain (fetal)	100.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	9.0
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	11.0
Lung ca. NCI-H522	7.6	Brain (Substantia nigra) Pool	6.1
Liver	0.0	Brain (Thalamus) Pool	22.4
Fetal Liver	5.1	Brain (whole)	7.8
Liver ca. HepG2	0.0	Spinal Cord Pool	13.7
Kidney Pool	14.0	Adrenal Gland	0.0
Fetal Kidney	2.1	Pituitary gland Pool	0.0
Renal ca. 786-0	0.0	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	4.2	Pancreatic ca. CAPAN2	3.0
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[0771] CNS_neurodegeneration_v1.0 Summary: Ag6797 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0772] General_screening_panel_v1.6 Summary: Ag6797 Expression of this gene is limited to the fetal brain (CT=34). Thus, expression of this gene could be used as a marker of this tissue.

[0773] Panel 4.1D Summary: Ag6797 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0774] L. CG111293-05: Protoporphyrinogen Oxidase.

[0775] Expression of gene CG111293-05 was assessed using the primer-probe set Ag6798, described in Table LA. Results of the RTQ-PCR runs are shown in Table LB.

TABLE LA
Probe Name Ag6798
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tgcctgtccaggtgatgct-3′	19	1254	205
Probe	TET-5′-agcctccagtgtctgtaaccaggaacctcc-3′-TAMRA	30	1274	206
Reverse	5′-tgaaacagctcctgagataagacaca-3′	26	1310	207

[0776]

TABLE LB
General_screening_panel_v1.6
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6798,		Ag6798,
	Run		Run
Tissue Name	278017531	Tissue Name	278017531
Adipose	5.6	Renal ca. TK-10	52.5
Melanoma* Hs688(A).T	8.4	Bladder	24.3
Melanoma* Hs688(B).T	4.2	Gastric ca. (liver met.) NCI-N87	0.0
Melanoma* M14	28.3	Gastric ca. KATO III	9.7
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	4.8	Colon ca. SW480	16.4
Squamous cell carcinoma SCC-	0.0	Colon ca.* (SW480 met) SW620	4.2
4
Testis Pool	28.3	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	23.8	Colon ca. HCT-116	31.9
Prostate Pool	0.0	Colon ca. CaCo-2	20.6
Placenta	25.7	Colon cancer tissue	0.0
Uterus Pool	0.0	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	13.1	Colon ca. Colo-205	6.7
Ovarian ca. SK-OV-3	4.7	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	14.9
Ovarian ca. OVCAR-5	20.3	Small Intestine Pool	37.9
Ovarian ca. IGROV-1	6.3	Stomach Pool	23.7
Ovarian ca. OVCAR-8	14.6	Bone Marrow Pool	12.2
Ovary	14.9	Fetal Heart	25.7
Breast ca. MCF-7	0.0	Heart Pool	5.2
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	40.1
Breast ca. BT 549	9.3	Fetal Skeletal Muscle	12.3
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	0.0
Breast Pool	28.5	Thymus Pool	23.7
Trachea	23.7	CNS cancer (glio/astro) U87-MG	31.0
Lung	73.7	CNS cancer (glio/astro) U-118-	0.0
		MG
Fetal Lung	27.7	CNS cancer (neuro;met) SK-N-AS	0.0
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	21.5
Lung ca. LX-1	33.9	CNS cancer (astro) SNB-75	44.1
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	25.2
Lung ca. SHP-77	20.4	CNS cancer (glio) SF-295	11.7
Lung ca. A549	0.0	Brain (Amygdala) Pool	50.7
Lung ca. NCI-H526	37.4	Brain (cerebellum)	63.3
Lung ca. NCI-H23	32.3	Brain (fetal)	20.9
Lung ca. NCI-H460	52.9	Brain (Hippocampus) Pool	55.9
Lung ca. HOP-62	9.3	Cerebral Cortex Pool	19.6
Lung ca. NCI-H522	52.1	Brain (Substantia nigra) Pool	62.9
Liver	0.0	Brain (Thalamus) Pool	35.6
Fetal Liver	100.0	Brain (whole)	29.1
Liver ca. HepG2	11.9	Spinal Cord Pool	64.2
Kidney Pool	37.6	Adrenal Gland	11.5
Fetal Kidney	18.7	Pituitary gland Pool	0.0
Renal ca. 786-0	4.7	Salivary Gland	6.3
Renal ca. A498	0.0	Thyroid (female)	7.5
Renal ca. ACHN	42.9	Pancreatic ca. CAPAN2	31.0
Renal ca. UO-31	5.7	Pancreas Pool	15.7

[0777] CNS_neurodegeneration_v1.0 Summary: Ag6798 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0778] General_screening_panel_v1.6 Summary: Ag6798 Expression of this gene is limited to fetal liver (CT=34.5). The relative overexpression of this gene in fetal skeletal muscle suggests that the protein product may enhance liver growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of liver related diseases.

[0779] Panel 4.1D Summary: Ag6798 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0780] M. CG111293-06: PPOX.

[0781] Expression of gene CG111293-06 was assessed using the primer-probe set Ag6809, described in Table MA.

TABLE MA
Probe Name Ag6809
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-caggccttggctgga-3′	15	929	208
Probe	TET-5′-agtcattaacagcaactccctcataggagg-3′-TAMRA	30	945	209
Reverse	5′-cccaggacactgactgct-3′	18	997	210

[0782] CNS_neurodegeneration_v1.0 Summary: Ag6809 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0783] General_screening_panel_v1.6 Summary: Ag6809 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0784] N. CG111455-01: Myosin Heavy Chain Like Gene

[0785] Expression of gene CG111455-01 was assessed using the primer-probe set Ag4443, described in Table NA. Results of the RTQ-PCR runs are shown in Tables NB, NC, ND and NE.

TABLE NA
Probe Name Ag4443
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ccagaagattctggaagaaagg-3′	22	2340	211
Probe	TET-5′-tgcacttattttgatccaatggaaca-3′-TAMRA	26	2364	212
Reverse	5′-ttcttcacagccatgaaagc-3′	20	2395	213

[0786]

TABLE NB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4443,		Ag4443,
	Run		Run
Tissue Name	224534978	Tissue Name	224534978
AD 1 Hippo	8.9	Control (Path) 3 Temporal Ctx	9.5
AD 2 Hippo	46.3	Control (Path) 4 Temporal Ctx	35.1
AD 3 Hippo	3.6	AD 1 Occipital Ctx	4.7
AD 4 Hippo	8.8	AD 2 Occipital Ctx (Missing)	0.0
AD 5 hippo	26.1	AD 3 Occipital Ctx	3.4
AD 6 Hippo	65.5	AD 4 Occipital Ctx	14.8
Control 2 Hippo	35.1	AD 5 Occipital Ctx	18.7
Control 4 Hippo	21.6	AD 6 Occipital Ctx	31.6
Control (Path) 3 Hippo	7.2	Control 1 Occipital Ctx	2.7
AD 1 Temporal Ctx	7.5	Control 2 Occipital Ctx	33.9
AD 2 Temporal Ctx	35.8	Control 3 Occipital Ctx	21.3
AD 3 Temporal Ctx	3.7	Control 4 Occipital Ctx	12.7
AD 4 Temporal Ctx	18.2	Control (Path) 1 Occipital Ctx	100.0
AD 5 Inf Temporal Ctx	37.4	Control (Path) 2 Occipital Ctx	17.3
AD 5 SupTemporal Ctx	36.1	Control (Path) 3 Occipital Ctx	0.8
AD 6 Inf Temporal Ctx	57.0	Control (Path) 4 Occipital Ctx	9.8
AD 6 Sup Temporal Ctx	42.6	Control 1 Parietal Ctx	11.6
Control 1 Temporal Ctx	17.3	Control 2 Parietal Ctx	29.3
Control 2 Temporal Ctx	27.5	Control 3 Parietal Ctx	16.6
Control 3 Temporal Ctx	16.3	Control (Path) 1 Parietal Ctx	48.6
Control 4 Temporal Ctx	10.5	Control (Path) 2 Parietal Ctx	33.4
Control (Path) 1 Temporal Ctx	44.4	Control (Path) 3 Parietal Ctx	4.6
Control (Path) 2 Temporal Ctx	33.4	Control (Path) 4 Parietal Ctx	38.2

[0787]

TABLE NC
General_screening_panel_v1.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4443,		Ag4443,
	Run		Run
Tissue Name	220005793	Tissue Name	220005793
Adipose	0.1	Renal ca. TK-10	0.7
Melanoma* Hs688(A).T	0.1	Bladder	0.3
Melanoma* Hs688(B).T	6.5	Gastric ca. (liver met.) NCI-N87	1.2
Melanoma* M14	0.0	Gastric ca. KATO III	0.4
Melanoma* LOXIMVI	18.8	Colon ca. SW-948	3.1
Melanoma* SK-MEL-5	0.5	Colon ca. SW480	1.7
Squamous cell carcinoma SCC-	3.0	Colon ca.* (SW480 met) SW620	0.2
4
Testis Pool	1.4	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	25.9	Colon ca. HCT-116	28.5
Prostate Pool	0.1	Colon ca. CaCo-2	0.1
Placenta	0.0	Colon cancer tissue	0.9
Uterus Pool	0.2	Colon ca. SW1116	0.3
Ovarian ca. OVCAR-3	1.2	Colon ca. Colo-205	0.4
Ovarian ca. SK-OV-3	5.6	Colon ca. SW-48	0.5
Ovarian ca. OVCAR-4	0.1	Colon Pool	0.1
Ovarian ca. OVCAR-5	0.7	Small Intestine Pool	0.5
Ovarian ca. IGROV-1	1.0	Stomach Pool	0.1
Ovarian ca. OVCAR-8	0.5	Bone Marrow Pool	0.1
Ovary	0.0	Fetal Heart	0.3
Breast ca. MCF-7	0.0	Heart Pool	0.2
Breast ca. MDA-MB-231	9.7	Lymph Node Pool	0.1
Breast ca. BT 549	100.0	Fetal Skeletal Muscle	0.2
Breast ca. T47D	0.4	Skeletal Muscle Pool	0.1
Breast ca. MDA-N	0.0	Spleen Pool	0.6
Breast Pool	0.1	Thymus Pool	0.5
Trachea	0.0	CNS cancer (glio/astro) U87-MG	17.6
Lung	0.2	CNS cancer (glio/astro) U-118-	3.0
		MG
Fetal Lung	0.1	CNS cancer (neuro;met) SK-N-AS	98.6
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.3
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-75	0.3
Lung ca. NCI-H146	0.5	CNS cancer (glio) SNB-19	1.0
Lung ca. SHP-77	0.4	CNS cancer (glio) SF-295	0.2
Lung ca. A549	1.2	Brain (Amygdala) Pool	2.2
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.5
Lung ca. NCI-H23	1.2	Brain (fetal)	0.6
Lung ca. NCI-H460	0.1	Brain (Hippocampus) Pool	2.9
Lung ca. HOP-62	0.2	Cerebral Cortex Pool	3.3
Lung ca. NCI-H522	0.1	Brain (Substantia nigra) Pool	2.1
Liver	0.0	Brain (Thalamus) Pool	4.2
Fetal Liver	0.3	Brain (whole)	0.9
Liver ca. HepG2	0.3	Spinal Cord Pool	4.6
Kidney Pool	0.3	Adrenal Gland	0.1
Fetal Kidney	0.4	Pituitary gland Pool	0.6
Renal ca. 786-0	0.4	Salivary Gland	0.0
Renal ca. A498	0.8	Thyroid (female)	0.8
Renal ca. ACHN	0.6	Pancreatic ca. CAPAN2	6.7
Renal ca. UO-31	1.9	Pancreas Pool	0.2

[0788]

TABLE ND
Panel 4.1D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4443,		Ag4443,
	Run		Run
Tissue Name	190820184	Tissue Name	190820184
Secondary Th1 act	0.0	HUVEC IL-1beta	26.6
Secondary Th2 act	28.1	HUVEC IFN gamma	15.9
Secondary Tr1 act	18.2	HUVEC TNF alpha + IFN gamma	35.1
Secondary Th1 rest	7.1	HUVEC TNF alpha + IL4	11.7
Secondary Th2 rest	0.0	HUVEC IL-11	15.5
Secondary Tr1 rest	0.0	Lung Microvascular EC none	13.4
Primary Th1 act	0.0	Lung Microvascular EC TNFalpha +	0.0
		IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC none	3.9
Primary Tr1 act	13.6	Microsvasular Dermal EC TNFalpha +	0.0
		IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium TNFalpha +	50.7
		IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	8.8
Primary Tr1 rest	15.7	Small airway epithelium TNFalpha +	26.8
		IL-1beta
CD45RA CD4 lymphocyte act	6.2	Coronery artery SMC rest	12.5
CD45RO CD4 lymphocyte act	22.7	Coronery artery SMC TNFalpha + IL-	26.2
		1beta
CD8 lymphocyte act	13.0	Astrocytes rest	27.4
Secondary CD8 lymphocyte rest	0.0	Astrocytes TNFalpha + IL-1beta	6.9
Secondary CD8 lymphocyte act	0.0	KU-812 (Basophil) rest	50.0
CD4 lymphocyte none	0.0	KU-812 (Basophil) PMA/ionomycin	72.2
2ry Th1/Th2/Tr1_anti-CD95	12.3	CCD1106 (Keratinocytes) none	29.3
CH11
LAK cells rest	0.0	CCD1106 (Keratinocytes) TNFalpha +	0.0
		IL-1beta
LAK cells IL-2	20.0	Liver cirrhosis	7.3
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IFN gamma	19.2	NCI-H292 IL-4	0.0
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells PMA/ionomycin	29.7	NCI-H292 IL-13	5.7
NK Cells IL-2 rest	20.7	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.0	HPAEC none	42.9
Two Way MLR 5 day	7.6	HPAEC TNF alpha + IL-1 beta	16.4
Two Way MLR 7 day	20.7	Lung fibroblast none	25.0
PBMC rest	6.7	Lung fibroblast TNF alpha + IL-1	28.1
		beta
PBMC PWM	13.3	Lung fibroblast IL-4	0.0
PBMC PHA-L	22.7	Lung fibroblast IL-9	26.6
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.0
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	8.3
B lymphocytes PWM	14.6	Dermal fibroblast CCD1070 rest	0.0
B lymphocytes CD40L and IL-4	17.7	Dermal fibroblast CCD1070 TNF	30.1
		alpha
EOL-1 dbcAMP	5.5	Dermal fibroblast CCD1070 IL-1 beta	11.8
EOL-1 dbcAMP PMA/ionomycin	16.3	Dermal fibroblast IFN gamma	13.3
Dendritic cells none	0.0	Dermal fibroblast IL-4	100.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	6.3
Dendritic cells anti-CD40	4.6	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	4.7	Colon	0.0
Macrophages rest	0.0	Lung	0.0
Macrophages LPS	0.0	Thymus	48.3
HUVEC none	12.2	Kidney	13.8
HUVEC starved	20.7

[0789]

TABLE NE
general oncology screening panel_v_2.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4443,		Ag4443,
	Run		Run
Tissue Name	268672172	Tissue Name	268672172
Colon cancer 1	3.5	Bladder NAT 2	0.0
Colon NAT 1	0.0	Bladder NAT 3	0.0
Colon cancer 2	100.0	Bladder NAT 4	0.0
Colon NAT 2	0.9	Prostate adenocarcinoma 1	6.6
Colon cancer 3	9.8	Prostate adenocarcinoma 2	1.3
Colon NAT 3	1.6	Prostate adenocarcinoma 3	1.5
Colon malignant cancer 4	27.5	Prostate adenocarcinoma 4	28.9
Colon NAT 4	0.0	Prostate NAT 5	0.0
Lung cancer 1	0.9	Prostate adenocarcinoma 6	1.1
Lung NAT 1	1.3	Prostate adenocarcinoma 7	0.0
Lung cancer 2	35.4	Prostate adenocarcinoma 8	0.0
Lung NAT 2	2.3	Prostate adenocarcinoma 9	1.4
Squamous cell carcinoma 3	4.9	Prostate NAT 10	0.0
Lung NAT 3	1.3	Kidney cancer 1	11.1
Metastatic melanoma 1	1.4	Kidney NAT 1	2.9
Melanoma 2	0.0	Kidney cancer 2	42.9
Melanoma 3	1.8	Kidney NAT 2	4.1
Metastatic melanoma 4	4.8	Kidney cancer 3	41.2
Metastatic melanoma 5	1.4	Kidney NAT 3	0.0
Bladder cancer 1	0.0	Kidney cancer 4	1.6
Bladder NAT 1	0.0	Kidney NAT 4	0.0
Bladder cancer 2	1.3

[0790] CNS_neurodegeneration_v1.0 Summary: Ag4443 This expression profile confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.

[0791] General_screening_panel_v1.4 Summary: Ag4443 Highest expression of this gene is seen in a breast cancer cell line (CT=28.2). Prominent levels of expression are also seen in cell lines derived from brain cancer, colon cancer, prostate cancer and melanoma. Thus, expression of this gene could be used to differentiate between the breast cancer derived sample and other samples on this panel and as a marker of these cancers. Therapeutic modulation of the expression or function of this gene may be effective in the treatment of brain, breast, colon, prostate, and melanoma cancers.

[0792] This gene is also expressed at low but significant levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0793] Panel 4.1D Summary: Ag4443 Expression of this gene is limited to IL-4 treated dermal fibroblasts (CT=34.4). This expression suggests that this gene product may be involved in skin disorders, including psoriasis.

[0794] general oncology screening panel_v—2.4 Summary: Ag4443 Highest expression of this gene is seen in colon cancer (CT=32.9). In addition, this gene is more highly expressed in colon and kidney cancer than in the corresponding normal adjacent tissue. Thus, expression of this gene could be used as a marker of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of colon and kidney cancer.

[0795] O. CG112292-02: Aquaporin 2-like.

[0796] Expression of gene CG112292-02 was assessed using the primer-probe set Ag6791, described in Table OA. Results of the RTQ-PCR runs are shown in Table OB.

TABLE OA
Probe Name Ag6791
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tcttggccagtggtcat-3′	17	153	214
Probe	TET-5′-cccagctgtcgtcactggcaaatttg-3′-TAMRA	26	170	215
Reverse	5′-accggctgctctatgaat-3′	18	213	216

[0797]

TABLE OB
General_screening_panel_v1.6
                               Rel.
                               Exp.(%)
                               Ag6791,
                               Run
Tissue Name                    277640796
Adipose                        0.0
Melanoma*Hs688(A).T            0.0
Melanoma*Hs688(B).T            0.0
Melanoma*M14                   0.0
Melanoma*LOXIMVI               0.0
Melanoma*SK-MEL-5              0.0
Squamous cell carcinoma SCC-4  0.0
Testis Pool                    0.0
Prostate ca.*(bone met)PC-3    0.0
Prostate Pool                  0.0
Placenta                       0.0
Uterus Pool                    0.0
Ovarian ca. OVCAR-3            3.2
Ovarian ca. SK-OV-3            0.0
Ovarian ca. OVCAR-4            0.0
Ovarian ca. OVCAR-5            1.2
Ovarian ca. IGROV-1            0.0
Ovarian ca. OVCAR-8            0.0
Ovary                          0.0
Breast ca. MCF-7               0.0
Breast ca. MDA-MB-231          0.0
Breast ca. BT 549              0.0
Breast ca. T47D                0.0
Breast ca. MDA-N               0.0
Breast Pool                    0.0
Trachea                        0.0
Lung                           0.0
Fetal Lung                     0.0
Lung ca. NCI-N417              0.0
Lung ca. LX-1                  0.0
Lung ca. NCI-H146              0.0
Lung ca. SHP-77                0.0
Lung ca. A549                  0.0
Lung ca. NCI-H526              0.0
Lung ca. NCI-H23               0.0
Lung ca. NCI-H460              0.0
Lung ca. HOP-62                0.0
Lung ca. NCI-H522              0.0
Liver                          0.0
Fetal Liver                    0.0
Liver ca. HepG2                0.0
Kidney Pool                    00
Fetal Kidney                   100.0
Renal ca. 786-0                0.0
Renal ca. A498                 0 0
Renal ca. ACHN                 0.0
Renal ca. UO:31                0.0
Renal ca. TK-10                0.0
Bladder                        0.0
Gastric ca.(liver met.)NCI-N87 8.8
Gastric ca. KATO III           2.5
Colon ca. SW-948               0.0
Colon ca. SW480                0.0
Colon ca.*(SW480 met)SW620     0.0
Colon ca. HT29                 3.5
Colon ca. HCT-116              0.0
Colon ca. CaCo-2               0.0
Colon cancer tissue            0.0
Colon ca. SW1116               0.0
Colon ca. Colo-205             0.0
Colon ca. SW-48                0.0
Colon Pool                     0.0
Small Intestine Pool           0.0
Stomach Pool                   0.0
Bone Marrow Pool               0.0
Fetal Heart                    0.0
Heart Pool                     0.0
Lymph Node Pool                0.0
Fetal Skeletal Muscle          0.0
Skeletal Muscle Pool           0.0
Spleen Pool                    0.0
Thymus Pool                    0.0
CNS cancer(glio/astro)U87-MG   0.0
CNS cancer(gilo/astro)U-118-MG 0.0
CNS cancer(neuro;met)SK-N-AS   7.3
CNS cancer(astro)SF-539        0.0
CNS cancer(astro)SNB-75        0.0
CNS cancer(gilo)SNB-19         0.0
CNS cancer(gilo)SF-295         0.0
Brain(Amygdala)Pool            0.0
Brain(cerebellum)              0.0
Brain(fetal)                   0.0
Brain(Hippocampus)Pool         0.0
Cerebral Cortex Pool           0.0
Brain(Substantia nigra)Pool    1.2
Brain(Thalamus)Pool            0.0
Brain(whole)                   0.0
Spinal Cord Pool               0.0
Adrenal Gland                  0.0
Pituitary gland Pool           0.0
Salivary Gland                 0.0
Thyroid(female)                0.0
Pancreatic ca. CAPAN2          1.4
Pancreas Pool                  0.0

[0798] CNS_neurodegeneration_v1.0 Summary: Ag6791 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0799] General_screening_panel_v1.6 Summary: Ag6791 Significant expression is limited to fetal kidney (CT=33.4). Interestingly, this gene is expressed at much higher levels in fetal tissue when compared to expression in adult kidney (CT=40). This observation suggests that expression of this gene can be used to distinguish fetal from adult kidney. This gene is homologous to aquaporin, a water channels that is essential for vasopressin-dependent concentration of urine (Deen, Science Apr. 1, 1994;264(5155):92-5). In addition, the relative overexpression of this gene in fetal kidney suggests that the protein product may enhance growth or development in this organ in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of muscle related diseases. More specifically, treatment of weak or dystrophic muscle with the protein encoded by this gene could restore muscle mass or function.

[0800] Panel 4.1D Summary: Ag6791 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0801] P. CG112292-04: Aquaporin 2-like

[0802] Expression of gene CG112292-04 was assessed using the primer-probe set Ag6800, described in Table PA.

TABLE PA
Probe Name Ag6800
Primers	Sequences	Length	Start Position	SEQ ID No
Forward	5′-cctgctctctccataggcttct-3′	22	548	217
Probe	TET-5′-cgtggccctgggctccctcct-3′-TAMRA	21	571	218
Reverse	5′-ctcttggctggcggaaa-3′	17	608	219

[0803] CNS_neurodegeneration_v1.0 Summary: Ag6800 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0804] General_screening_panel_v1.6 Summary: Ag6800 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0805] Panel 4.1D Summary: Ag6800 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0806] Q. CG112292-05: Aquaporin 2-like

[0807] Expression of gene CG112292-05 was assessed using the primer-probe set Ag6787, described in Table QA.

TABLE QA
Probe Name Ag6787
Primers	Sequences	Length	Start Position	SEQ ID No
Forward	5′-tacagattgccatggcgttt-3′	20	131	220
Probe	TET-5′-tattggcaccctgggccacctc-3′-TAMRA	22	159	221
Reverse	5′-agcagccggtgtaatggat-3′	19	187	222

[0808] CNS_neurodegeneration_v1.0 Summary: Ag6787 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0809] General_screening_panel_v1.6 Summary: Ag6787 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0810] Panel 4.1D Summary: Ag6787 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0811] R. CG112722-01: Epoxide Hydrolase-like Protein

[0812] Expression of gene CG112722-01 was assessed using the primer-probe set Ag4458, described in Table RA. Results of the RTQ-PCR runs are shown in Tables RB, RC and RD.

TABLE RA
Probe Name Ag4458
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-aattctggatgaccacattagc-3′	22	981	223
Probe	TET-5′-ttcctgaatgcatacctgggcttcat-3′-TAMRA	26	1033	224
Reverse	5′-ctttccaactcaaaaggacttg-3′	22	1059	225

[0813]

TABLE RB
CNS_neurodegeneration_v1.0
                             Rel.
                             Exp.(%)
                             Ag4458,
                             Run
Tissue Name                  224621294
AD 1 Hippo                   2.9
AD 2 Hippo                   34.4
AD 3 Hippo                   21.6
AD 4 Hippo                   37.4
AD 5 Hippo                   49.0
AD 6 Hippo                   39.2
Control 2 Hippo              28.5
Control 4 Hippo              32.3
Control(Path)3 Hippo         2.9
Temporal Ctx                 18.9
AD 2 Temporal Ctx            39.5
AD 3 Temporal Ctx            6.7
AD 4 Temporal Ctx            54.0
AD 5 Inf Temporal Ctx        27.7
Ad 5 Sup Temporal Ctx        46.7
AD 6 Inf Temporal Ctx        23.7
AD 6 Sup Temporal Ctx        30.8
Control 1 Temporal Ctx       8.0
Control 2 Temporal Ctx       23.7
Control 3 Temporal Ctx       15.6
Control 3 Temporal Ctx       8.3
Control(Path)1 Temporal Ctx  68.3
Control(Path)2 Temporal Ctx  47.3
Control(Path)3 Temporal Ctx  1.4
Control(Path)4 Temporal Ctx  20.7
AD 1 Occipital Ctx           19.2
AD 2 Occipital Ctx(Missing)  0.0
AD 3 Occipital Ctx           8.5
AD 4 Occipital Ctx           18.0
AD 5 Occipital Ctx           20.6
AD 6 Occipital Ctx           3.2
Control 1 Occipital Ctx      6.3
Control 2 Occipital Ctx      39.5
Control 3 Occipital Ctx      16.2
Control 4 Occipital Ctx      15.9
Control(Path)1 Occipital Ctx 100.9
Control(Path)2 Occipital Ctx 9.5
Control(Path)3 Occipital Ctx 0.0
Control(Path)4 Occipital Ctx 24.8
Control 1 Parietal Ctx       8.5
Control 2 Parietal Ctx       33.7
Control 3 Parietal Ctx       25.3
Control(Path)1 Parietal Ctx  68.8
Control(Path)2 Parietal Ctx  19.8
Control(Path)3 Parietal Ctx  0.0
Control(Path)4 Parietal Ctx  73.2

[0814]

TABLE RC
General_screening_panel_v1.4
                               Rel.
                               Exp.(%)
                               Ag4458,
                               Run
Tissue Name                    220264404
Adipose                        0.0
Melanoma*Hs688(A).T            0.0
Melanoma*Hs688(B).T            0.0
Melanoma*M14                   0.0
Melanoma*LOXIMVI               0.0
Melanoma*SK-MEL-5              0.0
Squamous cell carcinoma SCC-4  6.8
Testis Pool                    10.7
Prostate ca.*(bone met)PC-3    0.0
Prostate Pool                  31.9
Placenta                       0.0
Uterus Pool                    0.0
Ovarian ca. OVCAR-3            0.0
Ovarian ca. SK-OV-3            0.0
Ovarian ca. OVCAR-4            0.0
Ovarian ca. OVCAR-5            15.3
Ovarian ca. IGROV-1            0.0
Ovarian ca. OVCAR-8            0.0
Ovary                          7.7
Breast ca. MCF-7               0.0
Breast ca. MDA-MB-231          0.0
Breast ca. BT 549              29.7
Breast ca. T47D                0.0
Breast ca. MDA-N               0.0
Breast Pool                    13.7
Trachea                        0.0
Lung                           5.6
Fetal Lung                     76.3
Lung ca. NCI-N417              0.0
Lung ca. LX-1                  0.0
Lung ca. NCI-H146              0.0
Lung ca. SHP-77                0.0
Lung ca. A549                  0.0
Lung ca. NCI-H526              0.0
Lung ca. NCI-H23               0.0
Lung ca. NCI-H460              0.0
Lung ca. HOP-62                0.0
Lung ca. NCI-H522              4.2
Liver                          0.0
Fetal Liver                    0.0
Liver ca. HepG2                0.0
Kidney Pool                    2.1
Fetal Kidney                   41.8
Renal ca. 786-0                0.0
Renal ca. A498                 0.0
Renal ca. ACHN                 6.0
Renal ca. UO-31                0.0
Renal ca. TK-10                0.0
Bladder                        0.0
Gastric ca.(liver met.)NCI-N87 0.0
Gastric ca. KATO III           0.0
Colon ca. SW-948               0.0
Colon ca. SW480                0.0
Colon ca.*(SW480 met)SW620     0.0
Colon ca. HT29                 0.0
Colon ca. HCT-116              0.0
Colon ca. CaCo-2               0.0
Colon cancer tissue            0.0
Colon ca. SW1116               0.0
Colon ca. Colo-205             0.0
Colon ca. SW-48                0.0
Colon Pool                     4.3
Small Intestine Pool           0.0
Stomach Pool                   0.0
Bone Marrow Pool               7.8
Fetal Heart                    13.8
Heart Pool                     2.7
Lymph Node Pool                2.7
Fetal Skeletal Muscle          27.9
Skeletal Muscle Pool           33.4
Spleen Pool                    0.0
Thymus Pool                    8.4
CNS cancer(glio/astro)U87-MG   0.0
CNS cancer(glio/astro)U-118-MG 43.8
CNS cancer(neuro;met)SK-N-AS   0.0
CNS cancer(astro)SF-539        0.0
CNS cancer(astro)SNB-75        0.0
CNS cancer(glio)SNB-19         0.0
CNS cancer(glio)SF-295         0.0
Brain(Amygdala)Pool            16.6
Brain(cerebellum)              11.0
Brain(fetal)                   91.4
Brain(Hippocampus)Pool         68.3
Cerebral Cortex Pool           81.8
Brain(Substantia nigra)Pool    23.7
Brain(Thalamus)Pool            82.9
Brain(whole)                   32.3
Spinal Cord Pool               100.0
Adrenal Gland                  2.6
Pituitary gland Pool           9.2
Salivary Gland                 0.0
Thyroid(female)                6.2
Pancreatic ca. CAPAN2          0.0
Pancreas Pool                  9.5

[0815]

TABLE RD
general oncology screening panel_v_2.4
                               Rel.
                               Exp.(%)
                               Ag4458,
                               Run
Tissue Name                    268672300
Colon cancer 1                 0.0
Colon cancer NAT 1             0.0
Colon cancer 2                 0.0
Colon cancer NAT 2             0.0
Colon cancer 3                 0.0
Colon cancer NAT 3             5.8
Colon malignant cancer 4       0.0
Colon normal adjacent tissue 4 0.0
Lung cancer 1                  0.0
Lung NAT 1                     0.0
Lung cancer 2                  16.2
Lung NAT 2                     4.9
Squamous cell carcinoma 3      0.0
Lung NAT 3                     0.0
metastatic melanoma 1          29.7
Melanoma 2                     0.0
Melanoma 3                     0.0
metastatic melanoma 4          24.0
metastatic melanoma 5          33.9
Bladder cancer 1               0.0
Bladder cancer NAT 1           0.0
Bladder cancer 2               4.5
Bladder cancer NAT 2           0.0
Bladder cancer NAT 3           0.0
Bladder cancer NAT 4           0.0
Prostate adenocarcinoma 1      86.5
Prostate adenocarcinoma 2      19.1
Prostate adenocarcinoma 3      78.5
Prostate adenocarcinoma 4      0.0
Prostate cancer NAT 5          5.5
Prostate adenocarcinoma 6      6.0
Prostate adenocarcinoma 7      26.4
Prostate adenocarcinoma 8      3.5
Prostate adenocarcinoma 9      100.0
Prostate cancer NAT 10         3.9
Kidney cancer 1                0.0
Kidney NAT 1                   5.9
Kidney cancer 2                2.5
Kidney NAT 2                   17.1
Kidney cancer 3                7.3
Kidney NAT 3                   0.0
Kidney cancer 4                0.0
Kidney NAT 4                   0.0

[0816] CNS_neurodegeneration_v1.0 Summary: Ag4458 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. See Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.

[0817] General_screening_panel_v1.4 Summary: Ag4458 Expression of the CG112722-01 gene is highest in spinal cord (CT=33.5). This gene is also expressed at low but significant levels in hippocampus, thalamus, and cerebral cortex. Therefore, expression of this gene may be used to distinguish these tissues from the other samples on this panel. Furthermore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0818] Panel 4.1D Summary: Ag4458 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0819] general oncology screening panel_v—2.4 Summary: Ag4458 Expression of the CG112722-01 gene is highest in a prostate tumor sample (CT=34.3). Expression of this gene appears to upregulated in a number of prostate tumors when compared to normal prostate tissue. Thus, expression of this gene may be used to distinguish prostate tumors. Furthermore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of prostate cancer.

[0820] S. CG112881-02: Angiotensin II Receptor

[0821] Expression of gene CG112881-02 was assessed using the primer-probe set Ag6801, described in Table SA. Results of the RTQ-PCR runs are shown in Table SB.

TABLE 5A
Probe Name Ag6801
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tccaagatgattgtcccaaa-3′	20	1802	226
Probe	TET-5′-tgacaaatatgtaattatgccttccagc-3′-TAMRA	28	1774	227
Reverse	5′-tccaaatattcccaccacaa-3′	20	1727	228

[0822]

TABLE SB
CNS_neurodegeneration_v1.0
                             Rel.
                             Exp.(%)
                             Ag6801,
                             Run
Tissue Name                  279032454
AD 1 Hippo                   0.0
AD 2 Hippo                   0.0
AD 3 Hippo                   0.0
AD 4 Hippo                   0.0
AD 5 hippo                   55.1
AD 6 Hippo                   0.0
Control 2 Hippo              0.0
Control 4 Hippo              0.0
Control(Path)3 Hippo         0.0
AD 1 Temporal Ctx            0.0
AD 2 Temporal Ctx            0.0
AD 3 Temporal Ctx            0.0
AD 4 Temporal Ctx            0.0
AD 5 Inf Temporal Ctx        94.6
AD 5 SupTemporal Ctx         75.8
AD 6 Inf Temporal Ctx        0.0
AD 6 Sup Temporal Ctx        0.0
Control 1 Temporal Ctx       0.0
Control 2 Temporal Ctx       0.0
Control 3 Temporal Ctx       0.0
Control 4 Temporal Ctx       0.0
Control(Path)1 Temporal Ctx  0.0
Control(Path)2 Temporal Ctx  0.0
Control(Path)3 Temporal Ctx  0.0
Control(Path)4 Temporal Ctx  0.0
AD 1 Occipital Ctx           0.0
AD 2 Occipital Ctx(Missing)  0.0
AD 3 Occipital Ctx           0.0
AD 4 Occipital Ctx           0.0
AD 5 Occipital Ctx           2.4
AD 6 Occipital Ctx           100.0
Control 1 Occipital Ctx      0.0
Control 2 Occipital Ctx      0.0
Control 3 Occipital Ctx      0.0
Control(Path)1 Occipital Ctx 0.0
Control(Path)1 Occipital Ctx 0.0
Control(Path)2 Occipital Ctx 0.0
Control(Path)3 Occipital Ctx 0.0
Control(Path)4 Occipital Ctx 0.0
Control 1 Parietal Ctx       0.0
Control 2 Parietal Ctx       68.8
Control 3 Parietal Ctx       0.0
Control(Path)1 Parietal Ctx  0.0
Control(Path)2 Parietal Ctx  0.0
Control(Path)3 Parietal Ctx  0.0
Control(Path)4 Parietal Ctx  0.0

[0823] CNS_neurodegeneration_v1.0 Summary: Ag6801 This gene is expressed at low levels in the CNS. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0824] T. CG113803-01: KIF21A

[0825] Expression of gene CG113803-01 was assessed using the primer-probe sets Ag964 and Ag4474, described in Tables TA and TB. Results of the RTQ-PCR runs are shown in Tables TC, TD, TE, TF and TG.

TABLE TA
Probe Name Ag964
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-aacatcaaatcctgttcccatt-3′	22	453	229
Probe	TET-5′-ccagctccagtttgtccataagcaaa-3′-TAMRA	26	415	230
Reverse	5′-ttgctttgaaggatacaatgct-3′	22	387	231

[0826]

TABLE TB
Probe Name Ag4474
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggtgtgggatatcagagattca-3′	22	4356	232
Probe	TET-5′-tgcattcgaacactaacgtcttcagg-3′-TAMRA	26	4384	233
Reverse	5′-cgactggtacttgcagaacaa-3′	21	4431	234

[0827]

TABLE TC
CNS_neurodegeneration_v1.0
                             Rel.
                             Exp.(%)
                             Ag4474,
                             Run
Tissue Name                  224535204
AD 1 Hippo                   13.6
AD 2 Hippo                   21.9
AD 3 Hippo                   4.7
AD 4 Hippo                   7.4
AD 5 hippo                   94.6
AD 6 Hippo                   54.0
Control 2 Hippo              28.5
Control 4 Hippo              8.4
Control(Path)3 Hippo         8.0
AD 1 Temporal Ctx            10.6
AD 2 Temporal Ctx            25.0
AD 3 Temporal Ctx            4.4
AD 4 Temporal Ctx            15.2
AD 5 Inf Temporal Ctx        100.0
AD 5 SupTemporal Ctx         37.4
AD 6 Inf Temporal Ctx        34.6
AD 6 Sup Temporal Ctx        39.5
Control 1 Temporal Ctx       5.0
Control 2 Temporal Ctx       36.1
Control 3 Temporal Ctx       9.0
Control 4 Temporal Ctx       6.2
Control(Path)1 Temporal Ctx  52.5
Control(Path)2 Temporal Ctx  46.0
Control(Path)3 Temporal Ctx  5.9
Control(Path)4 Temporal Ctx  29.1
AD 1 Occipital Ctx           15.2
AD 2 Occipital Ctx(Missing)  0.0
AD 3 Occipital Ctx           5.8
AD 4 Occipital Ctx           17.1
AD 5 Occipital Ctx           32.1
AD 6 Occipital Ctx           43.5
Control 1 Occipital Ctx      2.7
Control 2 Occipital Ctx      58.6
Control 3 Occipital Ctx      11.7
Control 4 Occipital Ctx      4.8
Control(Path)1 Occipital Ctx 74.7
Control(Path)2 Occipital Ctx 12.2
Control(Path)3 Occipital Ctx 3.8
Control(Path)4 Occipital Ctx 10.0
Control 1 Parietal Ctx       5.9
Control 2 Parietal Ctx       32.8
Control 3 Parietal Ctx       25.2
Control(Path)1 Parietal Ctx  82.4
Control(Path)2 Parietal Ctx  22.1
Control(Path)3 Parietal Ctx  5.6
Control(Path)4 Parietal Ctx  42.3

[0828]

TABLE TD
General_screening_panel_v1.4
                               Rel.
                               Exp.(%)
                               Ag4474,
                               Run
Tissue Name                    222655843
Adipose                        2.4
Melanoma*Hs688(A).T            0.8
Melanoma*Hs688(B).T            0.6
Melanoma*M14                   4.1
Melanoma*LOXIMVI               0.0
Melanoma*SK-MEL-5              15.6
Squamous cell carcinoma        5.3
Testis Pool                    3.1
Prostate ca.*(bone met)PC-3    8.0
Prostate Pool                  2.8
Placenta                       2.0
Uterus Pool                    0.9
Ovarian ca. OVCAR-3            7.1
Ovarian ca. SK-OV-3            17.0
Ovarian ca. OVCAR-4            7.1
Ovarian ca. OVCAR-5            11.9
Ovarian ca. IGROV-1            6.0
Ovarian ca. OVCAR-8            5.5
Ovary                          1.4
Breast ca. MCF-7               9.9
Breast ca. MDA-MB-231          6.7
Breast ca. BT 549              1.1
Breast ca. T47D                26.8
Breast ca. MDA-N               5.0
Breast Pool                    7.5
Trachea                        6.3
Lung                           0.6
Fetal Lung                     7.6
Lung ca. NCI-N417              6.5
Lung ca. LX-1                  19.2
Lung ca. NCI-H146              8.5
Lung ca. SHP-77                24.8
Lung ca. A549                  13.7
Lung ca. NCI-H526              5.7
Lung ca. NCI-H23               10.1
Lung ca. NCI-H460              26.1
Lung ca. HOP-62                2.0
Lung ca. NCI-H522              7.3
Liver                          0.8
Fetal Liver                    3.5
Liver ca. HepG2                14.0
Kidney Pool                    3.3
Fetal Kidney                   5.2
Renal ca. 786-0                24.3
Renal ca. A498                 5.3
Renal ca. ACHN                 14.9
Renal ca. UO-31                7.3
Renal ca. TK-10                18.3
Bladder                        7.0
Gastric ca.(liver met.)NCI-N87 16.0
Gastric ca. KATO III           17.9
Colon ca. SW-948               4.1
Colon ca. SW480                11.1
Colon ca.*(SW480 met)SW620     13.2
Colon ca. HT29                 10.7
Colon ca. HCT-116              23.0
Colon ca. CaCo-2               23.5
Colon cancer tissue            9.9
Colon ca. SW1116               3.8
Colon ca. Colo-205             2.1
Colon ca. SW-48                3.3
Colon Pool                     6.5
Small Intestine Pool           2.3
Stomach Pool                   23
Bone Marrow Pool               1.7
Fetal Heart                    8.0
Heart Pool                     3.0
Lymph Node Pool                7.0
Fetal Skeletal Muscle          0.5
Skeletal Muscle Pool           4.9
Spleen Pool                    2.5
Thymus Pool                    3.7
CNS cancer(glio/astro)U87-MG   5.5
CNS cancer(glio/astro)U-118-MG 9.5
CNS cancer(neuro;met)SK-N-AS   100.0
CNS cancer(astro)SF-539        2.2
CNS cancer(astro)SNB-75        3.9
CNS cancer(glio)SNB-19         6.2
CNS cancer(glio)SF-295         11.6
Brain(Amygdala)Pool            17.1
Brain(cerebellum)              17.7
Brain(fetal)                   19.3
Brain(Hippocampus)Pool         18.4
Cerebral Cortex Pool           26.4
Brain(Substantia nigra)Pool    25.7
Brain(Thalamus)Pool            43.8
Brain(whole)                   11.8
Spinal Cord Pool               17.9
Adrenal Gland                  2.6
Pituitary gland Pool           3.8
Salivary Gland                 1.6
Thyroid(female)                0.8
Pancreatic ca. CAPAN2          13.5
Pancreas Pool                  6.7

[0829]

TABLE TE
Panel 4.1D
                                 Rel.
                                 Exp.(%)
                                 Ag4474,
                                 Run
Tissue Name                      191882346
Secondary Th1 act                26.2
Secondary Th2 act                14.7
Secondary Tr1 act                11.3
Secondary Th1 rest               1.2
Secondary Th2 rest               2.7
Secondary Tr1 rest               2.0
Primary Th1 act                  6.4
Primary Th2 act                  6.6
Primary Tr1 act                  14.5
Primary Th1 rest                 2.7
Primary Th2 rest                 1.2
Primary Tr1 rest                 3.5
CD45RA CD4                       16.8
lymphocyte act
CD45RO CD4                       46.3
lymphocyte act
CD8 lymphocyte act               51.8
Secondary CD8                    44.1
lymphocyte rest
Secondary CD8                    25.5
lymphocyte act
CD4 lymphocyte none              5.9
2ry Th1/Th2/Tr1_anti-            6.3
CD95 CH11
LAK cells rest                   11.6
LAK cells IL-2                   30.6
LAK cells IL-2 + IL-12           21.5
LAK cells IL-2 + IFN             25.2
gamma
LAK cells IL-2 + IL-18           25.7
LAK cells                        35.1
PMA/ionomycin
NK Cells IL-2 rest               55.9
Two Way MLR 3 day                17.3
Two Way MLR 5 day                32.5
Two Way MLR 7 day                28.1
PBMC rest                        3.7
PBMC PWM                         49.0
PBMC PHA-L                       34.6
Ramos(B cell)none                0.0
Ramos(B cell)1                   0.0
Ionomycin
B lymphocytes PWM                21.5
B lymphocytes CD40L              3.6
and IL-4
EOL-1 dbcAMP                     0.5
EOL-1 dbcAMP                     0.8
PMA/ionomycin
Dendritic cells none             4.9
Dendritic cells LPS              3.3
Dendritic cells anti-CD40        2.1
Monocytes rest                   0.6
Monocytes LPS                    1.2
Macrophages rest                 12.7
Macrophages LPS                  2.0
HUVEC none                       14.3
HUVEC starved                    17.2
HUVEC IL-1beta                   15.4
HUVEC IFN gamma                  10.9
HUVEC TNF alpha + IFN gamma      6.7
HUVEC TNF alpha + IL4            15.2
HUVEC IL-11                      6.5
Lung Microvascular EC none       24.7
Lung Microvascular EC            21.6
TNFalpha + IL-1beta
Microvascular Dermal EC none     11.3
Microsvasular Dermal EC          11.3
TNFalpha + IL-1beta
Bronchial epithelium             39.0
TNFalpha + IL1beta
Small airway epithelium none     9.0
Small airway epithelium          31.6
TNFalpha + IL-1beta
Coronery artery SMC rest         8.3
Coronery artery SMC              5.7
TNFalpha + IL-1beta
Astrocytes rest                  15.0
Astrocytes TNFalpha +            18.9
IL-1beta
KU-812(Basophil)rest             4.1
KU-812(Basophil)                 8.2
PMA/ionomycin
CCD1106(Keratinocytes)none       29.9
CCD1106(Keratinocytes)           26.8
TNFalpha + IL-1beta
Liver cirrhosis                  15.9
NCI-H292 none                    27.4
NCI-H292 IL-4                    29.5
NCI-H292 IL-9                    55.1
NCI-H292 IL-13                   36.6
NCI-H292 IFN gamma               28.5
HPAEC none                       10.6
HPAEC TNF alpha + IL-1 beta      15.0
Lung fibroblast none             11.1
Lung fibroblast TNF alpha + IL-1 beta 3.4
Lung fibroblast IL-4             4.0
Lung fibroblast IL-9             7.2
Lung fibroblast IL-13            6.3
Lung fibroblast IFN              2.8
gamma
Dermal fibroblast                4.8
CCD1070 rest
Dermal fibroblast                22.8
CCD1070 TNF alpha
Dermal fibroblast                5.5
Dermal fibroblast                3.0
gamma
Dermal fibroblast IL-4           5.9
Dermal Fibroblasts rest          3.5
Neutrophils TNFa + LPS           0.8
Neutrophils rest                 0.5
Colon                            10.4
Lung                             1.7
Thymus                           4.4
Kidney                           100.0

[0830]

TABLE TF
Panel CNS_1.1
                           Rel.
                           Exp.(%)
                           Ag4474,
                           Run
Tissue Name                198360862
Cing Gyr Depression2       7.9
Cing Gyr Depression        6.7
Cing Gyr PSP2              5.9
Cing Gyr PSP               16.3
Cing Gyr Huntington's2     15.2
Cing Gyr Huntington's      58.6
Cing Gyr Parkinson's2      22.4
Cing Gyr Parkinson's       36.3
Cing Gyr Alzheimer's2      7.0
Cing Gyr Alzheimer's       17.0
Cing Gyr Control2          36.3
Cing Gyr Control           76.3
Temp Pole Depression2      5.9
Temp Pole PSP2             3.6
Temp Pole PSP              2.1
Temp Pole Huntington's     28.1
Temp Pole Parkinson's2     22.1
Temp Pole Parkinson's      15.1
Temp Pole Alzheimer's2     5.0
Temp Pole Alzheimer's      2.9
Temp Pole Control2         52.5
Temp Pole Control          14.0
Glob Palladus Depression   3.4
Glob Palladus PSP2         3.8
Glob Palladus PSP          2.9
Glob Palladus Parkinson's2 6.8
Glob Palladus Parkinson's  53.2
Glob Palladus Alzheimer's2 4.1
Glob Palladus Alzheimer's  10.7
Glob Palladus Control2     5.4
Glob Palladus Control      6.7
Sub Nigra Depression2      9.3
Sub Nigra Depression       6.3
Sub Nigra PSP2             6.3
Sub Nigra Huntington's2    54.7
Sub Nigra Huntington's     58.2
Sub Nigra Parkinson's2     64.6
Sub Nigra Alzheimer's2     15.6
Sub Nigra Control2         22.8
Sub Nigra Control          44.1
BA17 Depression2           17.6
BA17 Depression            8.8
BA17 PSP2                  9.8
BA17 PSP                   22.5
BA17 Huntington's2         13.4
BA17 Huntington's          25.0
BA17 Parkinson's2          43.8
BA17 Parkinson's           24.1
BA17 Alzheimer's2          4.4
BA17 Control2              59.5
BA17 Control               42.0
BA9 Depression2            8.2
BA9 Depression             3.9
BA9 PSP2                   12.5
BA9 PSP                    12.5
BA9 Huntington's2          9.7
BA9 Huntington's           47.0
BA9 Parkinson's2           55.9
BA9 Parkinson's            26.2
BA9 A1zheimer's2           8.1
BA9 Alzheimer's            5.4
BA9 Control2               93.3
BA9 Control                26.8
BA7 Depression             6.4
BA7 PSP2                   33.2
BA7 PSP                    32.5
BA7 Huntington's2          25.3
BA7 Huntington's           35.4
BA7 Parkinson's2           29.5
BA7 Parkinson's            14.4
BA7 Alzheimer's2           6.3
BA7 Control2               52.1
BA7 Control                36.1
BA4 Depression2            7.7
BA4 Depression             13.6
BA4 PSP2                   21.6
BA4 PSP                    7.4
BA4 Huntington's2          4.9
BA4 Huntington's           38.2
BA4 Parkinson's2           100.0
BA4 Parkinson's            46.7
BA4 Alzheimer's2           5.4
BA4 Control2               55.5
BA4 Control                37.6

[0831]

TABLE TG
general oncology screening panel_v_2.4
                               Rel.
                               Exp.(%)
                               Ag4474,
                               Run
Tissue Name                    268695118
Colon cancer 1                 15.2
Colon cancer NAT 1             6.2
Colon cancer 2                 14.0
Colon cancer NAT 2             10.4
Colon cancer 3                 22.8
Colon cancer NAT 3             17.2
Colon malignant cancer 4       34.4
Colon normal adjacent tissue 4 2.2
Lung cancer 1                  3.6
Lung NAT 1                     0.0
Lung cancer 2                  43.2
Lung NAT 2                     1.1
Squamous cell carcinoma 3      47.3
Lung NAT 3                     1.0
mestastatic melanoma 1         19.9
Melanoma 2                     1.0
Melanoma 3                     1.9
metastatic melanoma 4          14.6
metastatic melanoma 5          13.5
Bladder cancer 1               1.1
Bladder cancer NAT 1           0.0
Bladder cancer 2               2.0
Bladder cancer NAT 2           0.5
Bladder cancer NAT 3           0.5
Bladder cancer NAT 4           2.1
Prostate adenocarcinoma 1      14.3
Prostate adenocarcinoma 2      3.0
Prostate adenocarcinoma 3      9.2
Prostate adenocarcinoma 4      14.7
Prostate cancer NAT 5          1.0
Prostate adenocarcinoma 6      4.5
Prostate adenocarcinoma 7      3.3
Prostate adenocarcinoma 8      1.2
Prostate adenocarcinoma 9      17.9
Prostate cancer NAT 10         0.5
Kidney cancer 1                12.6
KidneyNAT 1                    5.0
Kidney cancer 2                100.0
Kidney NAT 2                   18.9
Kidney cancer 3                22.8
Kidney NAT 3                   5.5
Kidney cancer 4                9.4
Kidney NAT 4                   7.9

[0832] CNS_neurodegeneration_v1.0 Summary: Ag4474 This expression profile confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.

[0833] General_screening_panel_v1.4 Summary: Ag4474 Highest expression of this gene is seen in a brain cancer cell line (CT=26.2). This gene is widely expressed in this panel, with moderate expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0834] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0835] This gene is also expressed at high to moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0836] In addition, this gene is expressed at much higher levels in fetal lung tissue (CTs=30) when compared to expression in the adult counterpart (CTs=33.5). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.

[0837] Panel 4.1D Summary: Ag4474 Highest expression of this gene is seen in kidney (CT=29.3). This gene is also expressed at moderate to low levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0838] Panel CNS—1.1 Summary: Ag4474 This confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.

[0839] general oncology screening panel_v—2.4 Summary: Ag4474 This gene is widely expressed in this panel, with highest expression in kidney cancer (CT=28.7). In addition, this gene is more highly expressed in lung cancer than in the corresponding normal adjacent tissue. Thus, expression of this gene could be used as a marker of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of lung cancer.

[0840] U. CG113833-01: Retinoic Acid Receptor RXR-Alpha

[0841] Expression of gene CG113833-01 was assessed using the primer-probe set Ag6789, described in Table UA. Results of the RTQ-PCR runs are shown in Tables UB, UC and UD.

TABLE UA
Probe Name Ag6789
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gcgagctggggttcatag-3′	18	677	235
Probe	TET-5′-ctgccagtgctgaagcccagggt-3′-TAMRA	23	712	236
Reverse	5′-ggcccccactccatgt-3′	16	752	237

[0842]

TABLE UB
CNS_neurodegeneration—v1.0
                               Rel.
                               Exp.(%)
                               Ag6789,
                               Run
Tissue Name                    277731709
AD 1 Hippo                     36.1
AD 2 Hippo                     64.2
AD 3 Hippo                     33.2
AD 4 Hippo                     30.8
AD 5 hippo                     99.1
AD 6 Hippo                     90.1
Control 2 Hippo                46.7
Control 4 Hippo                67.8
Control (Path) 3 Hippo         24.3
AD 1 Temporal Ctx              35.1
AD 2 Temporal Ctx              50.3
AD 3 Temporal Ctx              41.8
AD 4 Temporal Ctx              30.1
AD 5 Inf Temporal Ctx          100.0
AD 5 SupTemporal Ctx           71.7
AD 6 Inf Temporal Ctx          76.3
AD 6 Sup Temporal Ctx          94.0
Control 1 Temporal Ctx         33.9
Control 2 Temporal Ctx         66.9
Control 3 Temporal Ctx         25.0
Control 4 Temporal Ctx         40.1
Control (Path) 1 Temporal Ctx  65.5
Control (Path) 2 Temporal Ctx  31.9
Control (Path) 3 Temporal Ctx  40.9
Control (Path) 4 Temporal Ctx  35.6
AD 1 Occipital Ctx             30.8
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             31.4
AD 4 Occipital Ctx             32.3
AD 5 Occipital Ctx             29.5
AD 6 Occipital Ctx             61.6
Control 1 Occipital Ctx        32.3
Control 2 Occipital Ctx        75.8
Control 3 Occipital Ctx        28.3
Control 4 Occipital Ctx        41.2
Control (Path) 1 Occipital Ctx 60.3
Control (Path) 2 Occipital Ctx 30.1
Control (Path) 3 Occipital Ctx 30.4
Control (Path) 4 Occipital Ctx 51.1
Control 1 Parietal Ctx         38.4
Control 2 Parietal Ctx         94.0
Control 3 Parietal Ctx         22.4
Control (Path) 1 Parietal Ctx  68.8
Control (Path) 2 Parietal Ctx  39.8
Control (Path) 3 Parietal Ctx  44.1
Control (Path) 4 Parietal Ctx  74.7

[0843]

TABLE UC
General_screening_panel_v1.6
                                 Rel.
                                 Exp.(%)
                                 Ag6789,
                                 Run
Tissue Name                      277640790
Adipose                          12.3
Melanoma*Hs688(A).T              14.0
Melanoma*Hs688(B).T              11.8
Melanoma*M14                     9.0
Melanoma*LOXIMVI                 3.0
Melanoma*SK-MEL-5                5.7
Squamous Cell carcinoma SCC-4    15.1
Testis Pool                      7.5
Prostate ca.*(bone met) PC-3     11.0
Prostate Pool                    4.9
Placenta                         28.5
Uterus Pool                      5.6
Ovarian ca. OVCAR-3              23.8
Ovarian ca. SK-OV-3              30.8
Ovarian ca. OVCAR-4              3.8
Ovarian ca. OVCAR-5              74.7
Ovarian ca. OGROV-1              10.7
Ovarian ca. OVCAR-8              12.2
Ovary                            8.7
Breast ca. MCF-7                 55.1
Breast ca. MDA-MB-231            44.1
Breast ca. BT 549                23.3
Breast ca. T47D                  14.0
Breast ca. MDA-N                 5.5
Breast Pool                      7.0
Trachea                          15.5
Lung                             2.1
Fetal Lung                       28.7
Lung ca. NCI-N417                7.6
Lung ca. LX-1                    13.7
Lung ca. NCI-H146                0.0
Lung ca. SHP-77                  3.4
Lung ca. A549                    14.2
Lung ca. NCI-H526                2.3
Lung ca. NCI-H23                 11.4
Lung ca. NCI-H460                24.3
Lung ca. HOP:62                  7.9
Lung ca. NCI-H522                14.0
Liver                            41.5
Fetal Liver                      46.3
Liver ca. HepG2                  17.2
Kidney Pool                      21.8
Fetal Kidney                     15.3
Renal ca. 786-0                  41.5
Renal ca. A498                   9.8
Renal ca. ACHN                   4.5
Renal ca. UO-31                  6.7
Renal ca. TK-10                  42.3
Bladder                          17.7
Gastric ca. (liver met.) NCI-N87 100.0
Gastric ca. KATO III             42.3
Colon ca. SW-948                 8.0
Colon ca. SW480                  46.7
Colon ca.*(SW480 met)SW620       11.2
Colon ca. HT29                   26.4
Colon ca. HCT-116                29.5
Colon ca. CaCo-2                 47.0
Colon cancer tissue              16.3
Colon ca. SW1116                 6.5
Colon ca. Colo-205               9.0
Colon ca. SW-48                  6.3
Colon Pool                       7.9
Small Intestine Pool             8.7
Stomach Pool                     4.2
Bone Marrow Pool                 2.1
Fetal Heart                      7.3
Heart Pool                       4.1
Lymph Node Pool                  9.3
Fetal Skeletal Muscle            8.5
Skeletal Muscle Pool             9.6
Spleen Pool                      11.9
Thymus Pool                      8.8
CNS cancer (glio/astro) U87-MG   18.9
CNS cancer (glio/astro) U-118-MG 29.3
CNS cancer (neuro;met) SK-N-AS   10.9
CNS cancer (astro) SF-539        30.6
CNS cancer (astro) SNB-75        65.5
CNS cancer (glio) SNB-19         8.1
CNS cancer (glio) SF-295         27.7
Brain (Amygdala) Pool            4.6
Brain (cerebellum)               3.8
Brain (fetal)                    8.9
Brain (Hippocampus) Pool         7.1
Cerebral Cortex Pool             4.0
Brain (Substantia nigra) Pool    4.8
Brain (Thalamus) Pool            7.6
Brain (whole)                    6.8
Spinal Cord Pool                 11.3
Adrenal Gland                    33.7
Pituitary gland Pool             5.4
Salivary Gland                   7.7
Thyroid (female)                 12.7
Pancreatic ca. CAPAN2            27.5
Pancreas Pool                    7.7

[0844]

TABLE UD
Panel 5 Islet
                               Rel.
                               Exp.(%)
                               Ag6789,
                               Run
Tissue Name                    279371000
97457_Patient-                 20.7
02go_adipose
97476_Patient-                 0.0
07sk_skeletal muscle
97477_Patient-                 8.6
07ut_uterus
97478_Patient-                 13.5
07pl_placenta
99167_Bayer Patient 1          26.8
97482_Patient-                 5.4
08ut_uterus
97483_Patient-                 9.1
08pl_placenta
97486_Patient-                 10.5
09sk_skeletal muscle
97487_Patient-                 3.4
09ut_uterus
97488_Patient-                 7.8
09pl_placenta
97492_Patient-                 4.0
10ut_uterus
97493_Patient-                 27.2
10pl_placenta
97495_Patient-                 8.6
11go_adipose
97496_Patient-                 17.0
11sk_skeletal muscle
97497_Patient-                 15.9
11ut_uterus
97498_Patient-                 11.3
11pl_placenta
97500_Patient-                 19.9
12go_adipose
97501_Patient-                 37.4
12sk_skeletal_muscle
97502_Patient-                 10.9
12ut_uterus
97503_Patient-                 47.0
12pl_placenta
94721_Donor 2 U-               31.9
A_Mesenchymal Stem
Cells
94722_Donor 2 U -              29.3
B_Mesenchymal Stem
Cells
94723_Donor 2 U -              34.9
C_Mesenchymal Stem
Cells
94709_Donor 2 AM - A_adipose   29.3
94710_Donor 2 AM - B_adipose   17.2
94711_Donor 2 AM - C_adipose   18.9
94712_Donor 2 AD - A_adipose   33.4
94713_Donor 2 AD - B_adipose   62.0
94714_2 AD - C_adipose         23.8
94742_Donor 3 U -              10.3
A_Mesenchymal Stem Cells
94743_Donor 3 U -              11.6
B_Mesenchymal Stem Cells
94730_Donor 3 AM - A_adipose   46.0
94731_Donor 3 AM - B_adipose   100.0
94732_Donor 3 AM - C_adipose   62.9
94733_Donor 3 AD - A_adipose   91.4
94734_Donor 3 AD - B_adipose   83.5
94735_Donor 3 AD - C_adipose   32.1
77138_Liver_HepG2untreated     38.4
73556_Heart_Cardiac stromal    9.2
cells (primary)
81735_Small Intestine          7.9
72409_Kidney_Proximal          11.8
Convoluted Tubule
82685_Small intestine_Duodenum 10.7
90650_Adrenal_Adrenocortical   5.8
adenoma
72410_Kidney_HRCE              17.0
72411_Kidney_HRE               4.7
73139_Uterus_Uterine smooth    12.3
muscle cells

[0845] CNS_neurodegeneration_v1.0 Summary: Ag6789 This expression profile confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.

[0846] General_screening_panel_v1.6 Summary: Ag6789 Highest expression of this gene is seen in a gastric cancer cell line (CT=28.3). This gene is widely expressed in this panel, with moderate expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0847] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0848] This gene is also expressed at low but significant levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0849] Panel 5 Islet Summary: Ag6789 This gene is widely expressed in this panel, with highest expression in adipose (CT=33). Low but significant levels of expression are also seen in other tissues with metabolic function, including skeletal muscle and placenta. See Panel 1.4 for discussion of this gene in metabolic disease.

[0850] V. CG114150-01: Type I Membrane Protein

[0851] Expression of gene CG114150-01 was assessed using the primer-probe sets Ag6793 and Ag6804, described in Tables VA and VB. Results of the RTQ-PCR runs are shown in Tables VC, VD, VE and VF.

TABLE VA
Probe Name Ag6793
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggactgccatatcacaaaagat-3′	22	234	238
Probe	TET-5′-ttctcatcatgtgacactacaacttgttc-3′-TAMRA	29	256	239
Reverse	5′-attgaccccagttgctctct-3′	20	290	240

[0852]

TABLE VB
Probe Name Ag6804
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tttcttttctagcttactaatgaggaaag-3′	29	774	241
Probe	TET-5′-tttgtttgaccacctaactgctcgag-3′-TAMRA	26	804	242
Reverse	5′-taatacccaaatatacacctgaatgc-3′	26	830	243

[0853]

TABLE VC
CNS_neurodegeneration_v1.0
                               Rel.
                               Exp.(%)
                               Ag6793,
                               Run
Tissue Name                    277731715
AD 1 Hippo                     10.9
AD 2 Hippo                     21.6
AD 3 Hippo                     6.0
AD 4 Hippo                     5.6
AD 5 hippo                     100.0
AD 6 Hippo                     41.5
Control 2 Hippo                31.0
Control 4 Hippo                7.3
Control (Path) 3 Hippo         4.9
AD 1 Temporal Ctx              4.9
AD 2 Temporal Ctx              34.6
AD 3 Temporal Ctx              5.8
AD 4 Temporal Ctx              18.8
AD 5 Inf Temporal Ctx          94.6
AD 5 SupTemporal Ctx           33.4
AD 6 Inf Temporal Ctx          42.6
AD 6 Sup Temporal Ctx          53.6
Control 1 Temporal Ctx         4.7
Control 2 Temporal Ctx         38.2
Control 3 Temporal Ctx         17.6
Control 4 Temporal Ctx         7.9
Control (Path) 1 Temporal Ctx  62.0
Control (Path) 2 Temporal Ctx  49.0
Control (Path) 3 Temporal Ctx  4.5
Control (Path) 4 Temporal Ctx  45.4
AD 1 Occipital Ctx             19.2
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             5.1
AD 4 Occipital Ctx             21.5
AD 5 Occipital Ctx             18.0
AD 6 Occipital Ctx             49.0
Control 1 Occipital Ctx        2.4
Control 2 Occipital Ctx        66.9
Control 3 Occipital Ctx        27.5
Control 4 Occipital Ctx        5.4
Control (Path) 1 Occipital Ctx 82.9
(Path) 2 Occipital Ctx         15.3
Control (Path) 3 Occipital Ctx 2.5
Control (Path) 4 Occipital Ctx 22.2
Control 1 Parietal Ctx         3.9
Control 2 Parietal Ctx         31.9
Control 3 Parietal Ctx         18.9
Control (Path) 1 Parietal Ctx  64.2
Control (Path) 2 Parietal Ctx  30.4
Control (Path) 3 Parietal Ctx  3.8
Control (Path) 4 Parietal Ctx  25.0

[0854]

TABLE VD
General_screening_panel_v1.6
                                 Rel.
                                 Exp.(%)
                                 Ag6793,
                                 Run
Tissue Name                      277640800
Adipose                          1.9
Melanoma*Hs688(A).T              1.3
Melanoma*Hs688(B).T              1.7
Melanoma*M14                     5.8
Melanoma*LOXIMVI                 5.9
Melanoma*SK-MEL-5                89.5
Squamous cell carcinoma SCC-4    1.6
Testis Pool                      16.2
Prostate ca.*(bone met) PC-3     12.8
Prostate Pool                    3.3
Placenta                         11.3
Uterus Pool                      0.8
Ovarian ca. OVCAR-3              6.8
Ovarian ca. SK-OV-3              5.8
Ovarian ca. OVCAR-4              0.5
Ovarian ca. OVCAR-5              8.5
Ovarian ca. IGROV-1              19.8
Ovarian ca. OVCAR-8              12.5
Ovary                            2.9
Breast ca. MCF-7                 6.0
Breast ca. MDA-MB-231            2.3
Breast ca. BT 549                3.2
Breast ca. T47D                  4.9
Breast ca. MDA-N                 0.9
Breast Pool                      6.1
Trachea                          4.9
Lung                             0.9
Fetal                            11.2
Lung ca. NCI-N417                2.7
Lung ca. LX-1                    19.6
Lung ca. NCI-H146                7.5
Lung ca. SHP-77                  18.9
Lung ca. A549                    4.1
Lung ca. NCI-H526                12.8
Lung ca. NCI-H23                 15.5
Lung ca. NCI-H460                37.4
Lung ca. HOP-62                  6.9
Lung ca. NCI-H522                52.9
Liver                            0.1
Fetal Liver                      4.0
Liver ca. HepG2                  5.3
Kidney Pool                      3.8
Fetal Kidney                     5.8
Renal ca. 786-0                  4.0
Renal ca. A498                   2.1
Renal ca. ACHN                   4.9
Renal ca. UO-31                  7.8
Renal ca. TK-10                  17.3
Bladder                          3.0
Gastric ca. (liver met.) NCI-N87 12.2
Gastric ca. KATO III             10.2
Colon ca. SW-948                 3.3
Colon ca. SW480                  3.6
Colon ca.*(SW480 met)SW620       7.8
Colon ca. HT29                   2.2
Colon ca. HCT-116                35.4
Colon ca. CaCo-2                 4.4
Colon cancer tissue              3.1
Colon ca. SW1116                 3.1
Colon ca. Colo-205               2.8
Colon ca. SW-48                  3.8
Colon Pool                       4.1
Small Intestine Pool             3.1
Stomach Pool                     3.4
Bone Marrow Pool                 1.4
Fetal Heart                      3.4
Heart Pool                       1.5
Lymph Node Pool                  6.6
Fetal Skeletal Muscle            1.5
Skeletal Muscle Pool             1.1
Spleen Pool                      4.5
Thymus Pool                      5.9
CNS cancer (glio/astro) U87-MG   9.2
CNS cancer (glio/astro) U-118-MG 0.6
CNS cancer (neuro;met) SK-N-AS   17.8
CNS cancer astro SF-539          1.5
CNS cancer (astro) SNB-75        8.5
CNS cancer (glio) SNB-19         20.4
CNS cancer (glio) SF-295         22.4
Brain (Amygdala) Pool            17.4
Brain (cerebellum)               100.0
Brain (fetal)                    46.0
Brain (Hippocampus) Pool         24.8
Cerebral Cortex Pool             39.8
Brain (Substantia nigra) Pool    27.0
Brain (Thalamus) Pool            41.5
Brain (whole)                    29.9
Spinal Cord Pool                 14.7
Adrenal Gland                    3.2
Pituitary gland Pool             2.1
Salivary Gland                   2.2
Thyroid (female)                 2.9
Pancreatic ca. CAPAN2            2.7
Pancreas Pool                    1.9

[0855]

TABLE VE
Panel 4.1D
                                 Rel.
                                 Exp.(%)
                                 Ag6793,
                                 Run
Tissue Name                      277641337
Secondary Th1 act                24.8
Secondary Th2 act                31.4
Secondary Tr1 act                8.8
Secondary Th1 rest               7.4
Secondary Th2 rest               23.0
Secondary Tr1 rest               28.9
Primary Th1 act                  5.0
Primary Th2 act                  9.0
Primary Tr1 act                  15.1
Primary Th1 rest                 7.2
Primary Th2 rest                 7.9
Primary Tr1 rest                 1.7
CD45RA CD4 lymphocyte act        12.7
CD45RO CD4 lymphocyte act        30.6
CD8 lymphocyte act               8.0
Secondary CD8 lymphocyte rest    3.2
Secondary CD8 lymphocyte act     6.6
CD4 lymphocyte none              5.7
2ry Th1/Th2/Tr1_anti-CD95        6.2
CH11
LAK cells rest                   14.3
LAK cells IL-2                   1.7
LAK cells IL-2 + IL-12           3.8
LAK cells IL-2 + IFN gamma       3.1
LAK cells IL-2 + IL-18           4.1
LAK cells PMA/ionomycin          5.3
NK Cells IL-2 rest               36.6
Two Way MLR 3 day                0.0
Two Way MLR 5 day                3.9
Two Way MLR 7 day                19.8
PBMC rest                        4.0
PBMC PWM                         3.7
PBMC PHA-L                       7.5
Ramos (B cell) none              6.4
Ramos (B cell) ionomycin         46.7
B lymphocytes PWM                12.2
B lymphocytes CD40L and IL-4     31.6
EOL-1 dbcAMP                     2.3
EOL-1 dbcAMP                     0.0
PMA/ionomycin
Dendritic cells none             19.3
Dendritic cells LPS              6.6
Dendritic cells anti-CD40        4.8
Monocytes rest                   5.6
Monocytes LPS                    0.0
Macrophages rest                 4.7
Macrophages LPS                  3.6
HUVEC none                       28.1
HUVEC starved                    29.1
HUVEC IL-1beta                   24.0
HUVEC IFN gamma                  46.3
HUVEC TNF alpha + IFN gamma      4.5
HUVEC TNF alpha + IL4            21.2
HUVEC IL-11                      17.9
Lung Microvascular EC none       16.4
Lung Microvascular EC TNFalpha + 8.6
Microvascular Dermal EC none     8.2
Microsvasular Dermal EC          7.9
TNFalpha + IL-1beta
Bronchial epithelium TNFalpha +  19.9
IL1beta
Small airway epithelium none     6.7
Small airway epithelium TNFalpha + IL-1beta 16.2
Coronery artery SMC rest         23.3
Coronery artery SMC TNFalpha + IL-1beta 56.3
Astrocytes rest                  7.8
Astrocytes TNFalpha + IL-1beta   0.0
KU-812 (Basophil) rest           100.0
KU-812 (Basophil)                0.0
pma/ionomycin
CCD1106 (Keratinocytes) none     10.7
CCD1106 (Keratinocytes)          4.9
TNFalpha + IL-1beta
Liver cirrhosis                  0.0
NCI-H292 none                    15.5
NCI-H292 IL-4                    12.1
NCI-H292 IL-13                   20.6
NCI-H292 IFN gamma               3.3
HPAEC none                       15.0
HPAEC TNF alpha + IL-1 beta      45.7
Lung fibroblast none             10.1
Lung fibroblast TNF alpha + IL-1 beta 28.1
Lung fibroblast IL-4             1.4
Lung fibroblast IL-9             2.8
Lung fibroblast IL-13            6.3
Lung fibroblast IFN gamma        0.0
Dermal fibroblast CCD1070 rest   1.4
Dermal fibroblast CCD1070 TNF alpha 62.9
Dermal fibroblast CCD1070 IL-1 beta 5.6
Dermal fibroblast IFN gamma      2.7
Dermal fibroblast IL-4           2.1
Dermal Fibroblasts rest          4.0
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 3.4
Colon                            3.2
Lung                             2.5
Thymus                           19.9
Kidney                           28.9

[0856]

TABLE VF
Panel 5 Islet
                                 Rel.
                                 Exp.(%)
                                 Ag6793,
                                 Run
Tissue Name                      279371001
97457_Patient-02go_adipose       3.6
97476_Patient-07sk_skeletal      0.0
muscle
97477_Patient-07ut_uterus        2.9
97478_Patient-07pl_placenta      37.6
99167_Bayer Patient 1            3.2
97482_Patient-08ut_uterus        4.8
97483_Patient-08pl_placenta      63.3
97486_Patient-09sk_skeletal muscle 4.0
97487_Patient-09ut_uterus        5.1
97488_Patient-09pl_placenta      33.2
97492_Patient-10ut_uterus        4.2
97493_Patient-10pl_placenta      99.3
97495_Patient-11go_adipose       3.8
97496_Patient-11sk_skeletal      6.5
muscle
97497_Patient-11ut_uterus        7.1
97498_Patient-11pl_placenta      35.4
97500_Patient-12go_adipose       6.3
97501_Patient-12sk_skeletal      13.0
muscle
97502_Patient-12ut_uterus        7.1
97503_Patient-12pl_placenta      100.0
94721_Donor 2 U-                 3.3
A_Mesenchymal Stem Cells
94722_Donor 2 U -                2.5
B_Mesenchymal Stem Cells
94722_Donor 2 U -                1.8
C_Mesenchymal Stem Cells
94709_Donor 2 AM - A_adipose     3.5
94710_Donor 2 AM - B_adipose     2.6
94711_Donor 2 AM - C_adipose     0.9
94712_Donor 2 AD - A_adipose     3.0
94713_Donor 2 AD - B_adipose     11.6
94714_Donor 2 AD - C_adipose     7.3
94742_Donor 3 U - A_Mesenchymal Stem 1.5
Donor 3 U - B_Mesenchymal Stem Cells 0.6
94730_Donor 3 AM - A_adipose     3.2
94731_Donor 3 AM - B_adipose     2.1
94732_Donor 3 AM - C_adipose     3.6
94733_Donor 3 AD - A_adipose     2.0
94734_Donor 3 AD - B_adipose     4.5
94735_Donor 3 AD - C_adipose     1.8
77138_Liver_HepG2untreated       51.4
73556_Heart_Cardiac stromal cells 6.2
(primary)
81735_Small Intestine            28.5
72409 Kidney_Proximal Convoluted 20.9
Tubule
82685_Small intestine_Duodenum   27.2
90650_Adrenal_Adrenocortical adenoma 3.2
72410_Kidney_HRCE                10.4
72411_Kidney_HRE                 3.2
73139_Uterus_Uterine smooth muscle 6.9
cells

[0857] CNS_neurodegeneration_v1.0 Summary: Ag6793 This expression profile confirms the presence of this gene in the brain. See Panel 1.6 for discussion of this gene in the central nervous system. Ag6804 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0858] General_screening_panel_v1.6 Summary: Ag6793 Highest expression of the gene in this panel is detected in the cerebellum (CT=27.2). In addition, moderate levels of expression are seen in all regions of the CNS examined. Therefore, the High expression in the cerebellum suggests that CG96412 may be a useful and specific target of drugs for the treatment of CNS disorders that have this brain region as the site of pathology, such as autism and the ataxias. In addition, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0859] Overall, this gene is widely expressed in this panel, with high levels of expression seen in a melanoma cell line and moderate levels of expression seen in the other cell lines on this panel. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0860] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0861] Ag6804 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0862] Panel 4.1D Summary: Ag6793 Highest expression of this gene is seen in resting basophils (CT=33.4). Low but significant levels of expression are also seen in activated dermal fibroblasts, lung fibroblasts, and coronary artery SMCs, IFN gamma treated HUVECs, resting NK cells, and ionomycin treated Ramos B cells. Ag6804 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0863] Panel 5 Islet Summary: Ag6793 Expression of this gene in this panel is limited to a few samples, with expression seen mainly in placenta.

[0864] W. CG114555-03: Facilitative Glucose Transporter Family Member GLUT9

[0865] Expression of gene CG114555-03 was assessed using the primer-probe set Ag5275, described in Table WA.

TABLE WA
Probe Name Ag5275
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggtggaaggagaagaaagca-3′	20	146	244
Probe	TET-5′-cctctacggagcacctcctctgcag-3′-TAMRA	25	167	245
Reverse	5′-gcactggccacatatgttgt-3′	20	203	246

[0866] CNS_neurodegeneration_v1.0 Summary: Ag5275 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0867] General_screening_panel_v1.5 Summary: Ag5275 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0868] Panel 4.1D Summary: Ag5275 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0869] X. CG114555-04: Facilitative Glucose Transporter Family Member GLUT9

[0870] Expression of gene CG114555-04 was assessed using the primer-probe set Ag5276, described in Table XA. Results of the RTQ-PCR runs are shown in Tables XB and XC.

TABLE XA
Probe Name Ag5276
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tcttctctggcatcccgtt-3′	19	1119	247
Probe	TET-5′-agttcttccagcaatctcagcggcc-3′-TAMRA	25	1152	248
Reverse	5′-caaagttggagagccagttga-3′	21	1203	249

[0871]

TABLE XB
General_screening_panel_v1.5
                                 Rel.
                                 Exp.(%)
                                 Ag5276,
                                 Run
Tissue Name                      230509500
Adipose                          1.4
Melanoma*Hs688(A).T              3.9
Melanoma*Hs688(B).T              1.3
Melanoma*M14                     0.0
Melanoma*LOXIMVI                 0.0
Melanoma*SK-MEL-5                0.0
Squamous cell carcinoma SCC-4    8.7
Testis Pool                      1.5
Prostate ca.*(bone met) PC-3     0.0
Prostate Pool                    4.1
Placenta                         5.3
Uterus Pool                      0.6
Ovarian ca. OVCAR-3              26.8
Ovarian ca. SK-OV-3              0.1
Ovarian ca. OVCAR-4              4.6
Ovarian ca. OVCAR-5              6.8
Ovarian ca. IGROV-1              0.1
Ovarian ca. OVCAR-8              1.3
Ovary                            3.5
Breast ca. MCF-7                 0.1
Breast ca. MDA-MB-231            0.1
Breast ca. BT 549                0.0
Breast ca. T47D                  0.2
Breast ca. MDA-N                 0.0
Breast Pool                      4.6
Trachea                          23.0
Lung                             1.0
Fetal Lung                       4.5
Lung ca. NCI-N417                0.0
Lung ca. LX-1                    1.2
Lung ca. NCI-H146                1.3
Lung ca. SHP-77                  0.5
Lung ca. A549                    0.2
Lung ca. NCI-H526                0.0
Lung ca. NCI-H23                 2.3
Lung ca. NCI-H460                0.0
Lung ca. HOP-62                  0.0
Lung ca. NCI-H522                0.0
Liver                            8.6
Fetal Liver                      100.0
Liver ca. HepG2                  48.3
Kidney Pool                      3.4
Fetal Kidney                     11.5
Renal ca. 786-0                  2.4
Renal ca. A498                   0.4
Renal ca. ACHN                   0.0
Renal ca. UO-31                  0.4
Renal ca. TK-10                  30.8
Bladder                          4.8
Gastric ca. (liver met.) NCI-N87 1.3
Gastric ca. KATO III             3.4
Colon ca. SW-948                 3.4
Colon ca. LSW480                 1.3
Colon ca.*(SW480 met)SW620       0.4
Colon ca. HT29                   1.0
Colon ca. HCT-116                2.5
Colon ca. CaCo-2                 26.6
Colon cancer tissue              6.4
Colon ca. SW1116                 0.1
Colon ca. Colo-205               0.4
Colon ca. SW-48                  1.5
Colon Pool                       4.3
Small Intestine Pool             1.1
Stomach Pool                     2.4
Bone Marrow Pool                 0.9
Fetal Heart                      2.7
Heart Pool                       1.1
Lymph Pool                       4.5
Fetal Skeletal Muscle            2.7
Skeletal Muscle Pool             2.2
Spleen Pool                      4.2
Thymus Pool                      4.8
CNS cancer (glio/astro) U87-MG   0.0
CNS cancer (glio/astro) U-118-MG 0.2
CNS cancer (neuro;met) SK-N-AS   0.0
CNS cancer (astro) SF-539        0.0
CNS cancer (astro) SNB-75        1.8
CNS cancer (glio) SNB-19         0.2
CNS cancer (glio) SF-295         1.5
Brain (Amygdala) Pool            1.3
Brain (cerebellum)               1.6
Brain (fetal)                    3.5
Brain (Hippocampus) Pool         2.7
Cerebral Cortex Pool             2.0
Brain (Substantia nigra) Pool    2.2
Brain (Thalamus) Pool            2.9
Brain (whole)                    3.3
Spinal Cord Pool                 6.0
Adrenal Gland                    4.7
Pituitary gland Pool             2.4
Salivary Gland                   28.3
Thyroid (female)                 6.1
Pancreatic ca. CAPAN2            0.9
Pancreas Pool                    5.9

[0872]

TABLE XC
Panel 4.1D
                                 Rel.
                                 Exp.(%)
                                 Ag5276,
                                 Run
Tissue Name                      230472865
Secondary Th1 act                1.5
Secondary Th2 act                1.8
Secondary Tr1 act                0.0
Secondary Th1 rest               0.0
Secondary Th2 rest               0.0
Secondary Tr1 rest               0.0
Primary Th1 act                  0.0
Primary Th2 act                  0.6
Primary Tr1 act                  0.0
Primary Th1 rest                 0.0
Primary Th2 rest                 0.0
Primary Tr1 rest                 0.0
CD45RA CD4 lymphocyte act        0.5
CD45RO CD4 lymphocyte act        0.4
CD8 lymphocyte act               0.0
Secondary CD8 lymphocyte rest    0.0
Secondary CD8 lymphocyte act     0.0
CD4 lymphocyte none              0.0
2ry Th1/Th2/Tr1_anti-CD95 CH11   0.0
LAK cells rest                   11.9
LAK cells IL-2                   0.0
LAK cells IL-2 + IL-12           0.9
LAK cells IL-2 + IFN gamma       1.5
LAK cells IL-2 + IL-18           0.0
LAK cells PMA/ionomycin          9.6
NK Cells IL-2 rest               0.0
Two Way MLR 3 day                7.4
Two Way MLR 5 day                0.0
Two Way MLR 7 day                0.0
PBMC rest                        6.8
PBMC PWM                         0.4
PBMC PHA-L                       1.1
Ramos (B cell) none              5.8
Ramos (B cell) ionomycin         5.6
B lymphocytes PWM                0.4
B lymphocytes CD40L and IL-4     0.0
EOL-1 dbcAMP                     23.5
EOL-1 dbcAMP PMA/ionomycin       2.4
Dendritic cells none             33.4
Dendritic cells LPS              3.6
Dendritic cells anti-CD40        23.8
Monocytes rest                   14.7
Monocytes LPS                    3.5
Macrophages rest                 21.2
Macrophages LPS                  1.5
HUVEC none                       0.0
HUVEC starved                    0.0
HUVEC IL-1beta                   0.0
HUVEC IFN gamma                  7.7
HUVEC TNF alpha + IFN gamma      0.0
HUVEC TNF alpha + IL4            0.0
HUVEC IL-11                      0.0
Lung Microvascular none          10.4
Lung Microvascular EC TNFalpha + 0.0
IL-1beta
Microvascular Dermal EC none     0.0
Microsvasular Dermal EC          0.0
TNFalpha + IL-1beta
Bronchial epithelium TNFalpha +  9.2
IL1beta
Small airway epithelium none     22.4
Small airway epithelium TNFalpha + 46.7
IL-1beta
Coronery artery SMC rest         1.1
Coronery artery SMC TNFalpha +   1.9
IL-1beta
Astrocytes rest                  0.0
Astrocytes TNFalpha + IL-1beta   0.0
KU-812 (Basophil) rest           0.0
KU-812 (Basophil)                0.0
PMA/ionomycin
CCD1106 (Keratinocytes) none     64.6
CCD1106 (Keratinocytes)          27.4
TNFalpha + IL-1beta
Liver cirrhosis                  8.3
NCI-H292 none                    57.0
NCI-H292 IL-4                    35.4
NCI-H292 IL-9                    58.6
NCI-H292 IL-13                   46.0
NCI-H292 IFN gamma               53.6
HPAEC none                       0.0
HPAEC TNF alpha + IL-1 beta      0.0
Lung fibroblast none             2.0
Lung fibroblast TNF alpha + IL-1 beta 1.3
Lung fibroblast IL-4             1.9
Lung fibroblast IL-9             2.4
Lung fibroblast IL-13            0.4
Lung fibroblast IFN gamma        6.3
Dermal fibroblast CCD1070 rest   0.6
Dermal fibroblast CCD1070 TNF    3.1
alpha
Dermal fibroblast CCD1070 IL-1 beta 0.7
Dermal fibroblast IFN gamma      0.6
Dermal fibroblast IL-4           0.0
Dermal Fibroblasts rest          0.0
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 0.4
Colon                            0.3
Lung                             0.0
Thymus                           2.2
Kidney                           100.0

[0873] CNS_neurodegeneration_v1.0 Summary: Ag5276 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0874] General_screening_panel_v1.5 Summary: Ag5276 This gene, a glucose transporter 9 homolog, is predominantly expressed in liver derived tissue, with highest expression in fetal liver (CT=28). GLUT9 has been shown to facilitate the transport of glucose (Doege H, Biochem J Sep. 15, 2000;350 Pt 3:771-6). This gene is also expressed at low but significant levels in adipose, adult and fetal heart and skeletal muscle, pancreas, thyroid, adrenal and pituitary. Since the liver is responsible for gluconeogenesis, enhancing glucose uptake through this putative glucose transporter may produce a negative feedback loop that would decrease hepatic glucose production. This could result in a lowering of blood glucose, a major therapeutic goal for the treatment of Type II (non-insulin dependent) diabetes. The tissue distribution and predicted function of this gene suggest that enhancing the function of this gene product may restore balance to blood glucose levels in patients with Type II diabetes.

[0875] This gene is also expressed at low but significant levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0876] Panel 4.1D Summary: Ag5276 Highest expression of this gene is seen in the kidney (CT=31.2). Low but significant levels of expression are also seen in clusters of samples derived from eosinophils, dendritic cells, NCI-H292 pulmonary mucoepidermoid cells, keratinoncytes, small airway epithelium and resting macrophages and monocytes. Thus, expression of this gene could be used to differentiate the kidney sample from other samples on this panel. In addition, this expression profile suggests that this gene product may be involved in inflammatory or autoimmune diseases of the lung and skin.

[0877] Y. CG114784-01: Signal Peptidase Domain Containing Protein

[0878] Expression of gene CG114784-01 was assessed using the primer-probe set Ag6813, described in Table YA.

TABLE YA
Probe Name Ag6813
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-aaagcccaagtgatccaaaat-3′	21	219	250
Probe	TET-5′-cgaggattttgtctccttccaatccaatta-3′-TAMRA	30	258	251
Reverse	5′-gcttttaaagaaatctgatggactagt-3′	27	290	252

[0879] CNS_neurodegeneration_v1.0 Summary: Ag6813 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0880] General_screening_panel_v1.6 Summary: Ag6813 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0881] Panel 4.1D Summary: Ag6813 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0882] Z. CG114886-01: Mitochondrial Inner Membrane Protease Subnunit 2 Like Gene

[0883] Expression of gene CG114886-01 was assessed using the primer-probe set Ag4479, described in Table ZA. Results of the RTQ-PCR runs are shown in Tables ZB, ZC, ZD and ZE.

TABLE ZA
Probe Name Ag4479
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ccaaagaggtgacattgtgatt-3′	22	298	253
Probe	TET-5′-aaaagcccaagtgatccaacatcaaa-3′-TAMRA	26	323	254
Reverse	5′-ttgtctccttccaaaccagtta-3′	22	363	255

[0884]

TABLE ZB
CNS_neurodegeneration_v1.0
                               Rel.
                               Exp.(%)
                               Ag4479,
                               Run
Tissue Name                    224535657
AD 1 Hippo                     7.4
AD 2 Hippo                     11.7
AD 3 Hippo                     10.4
AD 4 Hippo                     14.6
AD 5 Hippo                     59.9
AD 6 Hippo                     60.3
Control 2 Hippo                14.1
Control 4 Hippo                16.6
Control (Path) 3 Hippo         10.1
AD 1 Temporal Ctx              22.7
AD 2 Temporal Ctx              20.7
AD 3 Temporal Ctx              3.8
AD 4 Temporal Ctx              40.1
AD 5 Inf Temporal Ctx          59.0
AD 5 Sup Temporal Ctx          42.6
AD 6 Inf Temporal Ctx          100.0
AD 6 Sup Temporal Ctx          77.4
Control 1 Temporal Ctx         12.6
Control 2 Temporal Ctx         17.9
Control 3 Temporal Ctx         17.2
Control 3 Temporal Ctx         6.3
Control (Path) 1 Temporal Ctx  49.0
Control (Path) 2 Temporal Ctx  13.6
Control (Path) 3 Temporal Ctx  10.2
Control (Path) 4 Temporal Ctx  36.1
AD 1 Occipital Ctx             10.2
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             5.7
AD 4 Occipital Ctx             14.5
AD 5 Occipital Ctx             33.4
AD 6 Occipital Ctx             14.3
Control 1 Occipital Ctx        5.0
Control 2 Occipital Ctx        35.6
Control 3 Occipital Ctx        32.5
Control 4 Occipital Ctx        17.0
Control (Path) 1 Occipital Ctx 59.5
Control (Path) 2 Occipital Ctx 7.0
Control (Path) 3 Occipital Ctx 3.0
Control (Path) 4 Occipital Ctx 21.5
Control 1 Parietal Ctx         6.5
Control 2 Parietal Ctx         41.5
Control 3 Parietal Ctx         16.7
Control (Path) 1 Parietal Ctx  22.8
Control (Path) 2 Parietal Ctx  28.1
Control (Path) 3 Parietal Ctx  2.4
Control (Path) 4 Parietal Ctx  51.1

[0885]

TABLE ZC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4479, Run		Ag4479, Run
Tissue Name	222655887	Tissue Name	222655887
Adipose	10.6	Renal ca. TK-10	31.2
Melanoma* Hs688(A).T	17.8	Bladder	49.0
Melanoma* Hs688(B).T	22.7	Gastric ca. (liver met.) NCI-N87	75.8
Melanoma* M14	14.1	Gastric ca. KATO III	45.1
Melanoma* LOXIMVI	14.4	Colon ca. SW-948	4.4
Melanoma* SK-MEL-5	11.4	Colon ca. SW480	17.9
Squamous cell carcinoma	11.1	Colon ca.* (SW480 met)	0.0
SCC-4		SW620
Testis Pool	14.0	Colon ca. HT29	18.3
Prostate ca.* (bone met) PC-3	44.1	Colon ca. HCT-116	31.6
Prostate Pool	16.4	Colon ca. CaCo-2	42.9
Placenta	5.5	Colon cancer tissue	10.0
Uterus Pool	22.8	Colon ca. SW1116	3.3
Ovarian ca. OVCAR-3	21.9	Colon ca. Colo-205	2.4
Ovarian ca. SK-OV-3	100.0	Colon ca. SW-48	2.1
Ovarian ca. OVCAR-4	16.4	Colon Pool	55.1
Ovarian ca. OVCAR-5	23.2	Small Intestine Pool	67.4
Ovarian ca. IGROV-1	9.2	Stomach Pool	34.4
Ovarian ca. OVCAR-8	12.4	Bone Marrow Pool	26.4
Ovary	19.1	Fetal Heart	51.1
Breast ca. MCF-7	16.5	Heart Pool	19.6
Breast ca. MDA-MB-231	52.5	Lymph Node Pool	78.5
Breast ca. BT 549	66.0	Fetal Skeletal Muscle	26.4
Breast ca. T47D	42.0	Skeletal Muscle Pool	17.3
Breast ca. MDA-N	14.5	Spleen Pool	22.1
Breast Pool	69.7	Thymus Pool	33.4
Trachea	51.8	CNS cancer (glio/astro) U87-	32.1
		MG
Lung	21.2	CNS cancer (glio/astro) U-118-	76.3
		MG
Fetal Lung	99.3	CNS cancer (neuro;met) SK-N-	23.0
		AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	14.7
Lung ca. LX-1	37.9	CNS cancer (astro) SNB-75	67.8
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	18.8
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	77.9
Lung ca. A549	21.3	Brain (Amygdala) Pool	4.4
Lung ca. NCI-H526	0.5	Brain (cerebellum)	16.7
Lung ca. NCI-H23	47.0	Brain (fetal)	15.6
Lung ca. NCI-H460	20.4	Brain (Hippocampus) Pool	6.0
Lung ca. HOP-62	7.2	Cerebral Cortex Pool	9.4
Lung ca. NCI-H522	21.0	Brain (Substantia nigra) Pool	7.0
Liver	0.6	Brain (Thalamus) Pool	8.6
Fetal Liver	7.9	Brain (whole)	9.0
Liver ca. HepG2	0.0	Spinal Cord Pool	12.3
Kidney Pool	88.3	Adrenal Gland	14.6
Fetal Kidney	52.9	Pituitary gland Pool	1.9
Renal ca. 786-0	14.6	Salivary Gland	9.7
Renal ca. A498	8.5	Thyroid (female)	0.8
Renal ca. ACHN	21.9	Pancreatic ca. CAPAN2	39.5
Renal ca. UO-31	20.4	Pancreas Pool	66.4

[0886]

TABLE ZD
Panel 4.1D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4479,		Ag4479,
	Run		Run
Tissue Name	193608829	Tissue Name	193608829
Secondary Th1 act	35.4	HUVEC IL-1beta	27.7
Secondary Th2 act	49.3	HUVEC IFN gamma	33.4
Secondary Tr1 act	57.0	HUVEC TNF alpha + IFN gamma	20.9
Secondary Th1 rest	6.5	HUVEC TNF alpha + IL4	13.7
Secondary Th2 rest	55.1	HUVEC IL-11	27.5
Secondary Tr1 rest	13.3	Lung Microvascular EC none	90.1
Primary Th1 act	18.9	Lung Microvascular EC TNFalpha +	47.0
		IL-1beta
Primary Th2 act	38.7	Microvascular Dermal EC none	37.1
Primary Tr1 act	46.7	Microsvasular Dermal EC	36.1
		TNFalpha + IL-1beta
Primary Th1 rest	18.6	Bronchial epithelium TNFalpha +	23.8
		IL1beta
Primary Th2 rest	1.8	Small airway epithelium none	13.6
Primary Tr1 rest	53.6	Small airway epithelium TNFalpha +	25.2
		IL-1beta
CD45RA CD4 lymphocyte act	46.7	Coronery artery SMC rest	8.7
CD45RO CD4 lymphocyte act	50.7	Coronery artery SMC TNFalpha +	7.4
		IL-1beta
CD8 lymphocyte act	10.5	Astrocytes rest	5.2
Secondary CD8 lymphocyte rest	46.0	Astrocytes TNFalpha + IL-1beta	16.2
Secondary CD8 lymphocyte act	16.6	KU-812 (Basophil) rest	45.7
CD4 lymphocyte none	19.3	KU-812 (Basophil)	100.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	39.5	CCD1106 (Keratinocytes) none	45.4
CH11
LAK cells rest	51.4	CCD1106 (Keratinocytes)	50.7
		TNFalpha + IL-1beta
LAK cells IL-2	42.9	Liver cirrhosis	45.1
LAK cells IL-2 + IL-12	39.0	NCI-H292 none	22.4
LAK cells IL-2 + IFN gamma	25.7	NCI-H292 IL-4	36.9
LAK cells IL-2 + IL-18	52.1	NCI-H292 IL-9	59.5
LAK cells PMA/ionomycin	24.1	NCI-H292 IL-13	35.4
NK Cells IL-2 rest	97.3	NCI-H292 IFN gamma	42.0
Two Way MLR 3 day	71.2	HPAEC none	22.7
Two Way MLR 5 day	37.9	HPAEC TNF alpha + IL-1 beta	62.9
Two Way MLR 7 day	27.2	Lung fibroblast none	23.7
PBMC rest	13.3	Lung fibroblast TNF alpha + IL-1	10.4
		beta
PBMC PWM	31.4	Lung fibroblast IL-4	17.7
PBMC PHA-L	25.3	Lung fibroblast IL-9	42.3
Ramos (B cell) none	34.9	Lung fibroblast IL-13	11.8
Ramos (B cell) ionomycin	6.0	Lung fibroblast IFN gamma	54.3
B lymphocytes PWM	14.9	Dermal fibroblast CCD1070 rest	50.3
B lymphocytes CD40L and IL-4	36.1	Dermal fibroblast CCD1070 TNF	66.0
		alpha
EOL-1 dbcAMP	52.1	Dermal fibroblast CCD1070 IL-1	30.8
		beta
EOL-1 dbcAMP	19.9	Dermal fibroblast IFN gamma	27.7
PMA/ionomycin
Dendritic cells none	30.8	Dermal fibroblast IL-4	92.7
Dendritic cells LPS	24.5	Dermal Fibroblasts rest	24.0
Dendritic cells anti-CD40	27.0	Neutrophils TNFa + LPS	0.0
Monocytes rest	23.0	Neutrophils rest	13.1
Monocytes LPS	53.6	Colon	7.9
Macrophages rest	36.6	Lung	0.0
Macrophages LPS	17.1	Thymus	42.3
HUVEC none	9.7	Kidney	20.6
HUVEC starved	40.9

[0887]

TABLE ZE
general oncology screening panel_v_2.4
	Rel. Exp. (%) Ag4479,		Rel. Exp. (%) Ag4479,
Tissue Name	Run 268695123	Tissue Name	Run 268695123
Colon cancer 1	1.6	Bladder NAT 2	0.0
Colon NAT 1	4.3	Bladder NAT 3	0.0
Colon cancer 2	8.9	Bladder NAT 4	8.1
Colon NAT 2	1.9	Prostate	33.2
		adenocarcinoma 1
Colon cancer 3	3.3	Prostate	7.7
		adenocarcinoma 2
Colon NAT 3	4.1	Prostate	3.0
		adenocarcinoma 3
Colon malignant	2.6	Prostate	26.2
cancer 4		adenocarcinoma 4
Colon NAT 4	2.3	Prostate NAT 5	4.7
Lung cancer 1	8.6	Prostate	3.2
		adenocarcinoma 6
Lung NAT 1	0.0	Prostate	5.8
		adenocarcinoma 7
Lung cancer 2	27.0	Prostate	2.3
		adenocarcinoma 8
Lung NAT 2	2.2	Prostate	15.4
		adenocarcinoma 9
Squamous cell	16.0	Prostate NAT 10	2.3
carcinoma 3
Lung NAT 3	3.1	Kidney cancer 1	23.3
Metastatic	11.3	Kidney NAT 1	7.1
melanoma 1
Melanoma 2	13.5	Kidney cancer 2	37.1
Melanoma 3	10.2	Kidney NAT 2	10.4
Metastatic	100.0	Kidney cancer 3	29.3
melanoma 4
Metastatic	48.3	Kidney NAT 3	2.3
melanoma 5
Bladder cancer 1	2.9	Kidney cancer 4	6.6
Bladder NAT 1	0.0	Kidney NAT 4	0.0
Bladder cancer 2	5.7

[0888] CNS_neurodegeneration_v1.0 Summary: Ag4479 This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. This gene appears to be slightly upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of the expression or function of this gene may decrease neuronal death and be of use in the treatment of this disease.

[0889] General_screening_panel_v1.4 Summary: Ag4479 Highest expression of this gene is seen in an ovarian cancer cell line (CT=31.5). This gene is widely expressed in this panel, with moderate expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0890] Among tissues with metabolic function, this gene is expressed at low but significant levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle and heart. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0891] This gene is also expressed at low but significant levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0892] Panel 4.1D Summary: Ag4479 Highest expression of this gene is seen in the PMA/ionomycin treated KU-812 basophil cell line (CT=34.1). This gene is also expressed at low but significant levels in a wide range of cell types of significance in the immune response in health and disease.

[0893] general oncology screening panel_v—2.4 Summary: Ag4479 This gene is widely expressed in this panel, with highest expression in metastatic melanoma (CT=33.3). Thus, expression of this gene could be used as a marker of this cancers. Furthermore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of melanoma.

[0894] AA. CG115411-01: Myosin Heavy Chain Protein IIB

[0895] Expression of gene CG115411-01 was assessed using the primer-probe set Ag4481, described in Table AAA. Results of the RTQ-PCR runs are shown in Tables AAB, AAC, AAD and AAE.

TABLE AAA
Probe Name Ag4481
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gggtgaaagagaagcgtaagaa-3′	22	1981	256
Probe	TET-5′-atcgttccagacggtgtcccagct-3′-TAMRA	24	2009	257
Reverse	5′-agcttgttgaggttctccttgt-3′	22	2035	258

[0896]

TABLE AAB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4481,		Ag4481,
	Run		Run
Tissue Name	224535696	Tissue Name	224535696
AD 1 Hippo	14.6	Control (Path) 3 Temporal Ctx	18.2
AD 2 Hippo	34.9	Control (Path) 4 Temporal Ctx	46.3
AD 3 Hippo	14.3	AD 1 Occipital Ctx	23.5
AD 4 Hippo	27.5	AD 2 Occipital Ctx (Missing)	0.0
AD 5 Hippo	39.5	AD 3 Occipital Ctx	9.4
AD 6 Hippo	42.6	AD 4 Occipital Ctx	40.1
Control 2 Hippo	52.1	AD 5 Occipital Ctx	34.4
Control 4 Hippo	22.7	AD 6 Occipital Ctx	28.3
Control (Path) 3 Hippo	23.2	Control 1 Occipital Ctx	10.1
AD 1 Temporal Ctx	33.0	Control 2 Occipital Ctx	56.6
AD 2 Temporal Ctx	32.5	Control 3 Occipital Ctx	28.5
AD 3 Temporal Ctx	11.4	Control 4 Occipital Ctx	21.0
AD 4 Temporal Ctx	45.7	Control (Path) 1 Occipital Ctx	100.0
AD 5 Inf Temporal Ctx	74.2	Control (Path) 2 Occipital Ctx	39.8
AD 5 Sup Temporal Ctx	40.9	Control (Path) 3 Occipital Ctx	5.4
AD 6 Inf Temporal Ctx	68.8	Control (Path) 4 Occipital Ctx	38.7
AD 6 Sup Temporal Ctx	74.2	Control 1 Parietal Ctx	25.2
Control 1 Temporal Ctx	16.6	Control 2 Parietal Ctx	57.8
Control 2 Temporal Ctx	26.2	Control 3 Parietal Ctx	21.3
Control 3 Temporal Ctx	21.0	Control (Path) 1 Parietal Ctx	64.2
Control 3 Temporal Ctx	26.2	Control (Path) 2 Parietal Ctx	49.0
Control (Path) 1 Temporal Ctx	57.8	Control (Path) 3 Parietal Ctx	10.0
Control (Path) 2 Temporal Ctx	52.1	Control (Path) 4 Parietal Ctx	66.4

[0897]

TABLE AAC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4481, Run		Ag4481, Run
Tissue Name	222665740	Tissue Name	222665740
Adipose	1.2	Renal ca. TK-10	0.2
Melanoma* Hs688(A).T	0.0	Bladder	0.3
Melanoma* Hs688(B).T	0.3	Gastric ca. (liver met.) NCI-N87	0.5
Melanoma* M14	0.0	Gastric ca. KATO III	0.1
Melanoma* LOXIMVI	0.2	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.9	Colon ca. SW480	82.9
Squamous cell carcinoma SCC-	0.0	Colon ca.* (SW480 met) SW620	70.7
4
Testis Pool	3.6	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.1	Colon ca. HCT-116	0.0
Prostate Pool	1.4	Colon ca. CaCo-2	0.6
Placenta	0.1	Colon cancer tissue	0.6
Uterus Pool	0.3	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.1	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.1	Colon ca. SW-48	3.2
Ovarian ca. OVCAR-4	0.0	Colon Pool	1.2
Ovarian ca. OVCAR-5	0.2	Small Intestine Pool	2.0
Ovarian ca. IGROV-1	0.1	Stomach Pool	0.3
Ovarian ca. OVCAR-8	0.1	Bone Marrow Pool	0.3
Ovary	0.3	Fetal Heart	100.0
Breast ca. MCF-7	0.2	Heart Pool	10.2
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	1.0
Breast ca. BT 549	0.2	Fetal Skeletal Muscle	8.8
Breast ca. T47D	0.5	Skeletal Muscle Pool	52.5
Breast ca. MDA-N	0.1	Spleen Pool	0.4
Breast Pool	1.3	Thymus Pool	0.6
Trachea	0.7	CNS cancer (glio/astro) U87-MG	0.1
Lung	0.1	CNS cancer (glio/astro) U-118-MG	0.2
Fetal Lung	1.2	CNS cancer (neuro;met) SK-N-AS	0.4
Lung ca. NCI-N417	0.0	CNS cancer (astro) SK-539	0.0
Lung ca. LX-1	52.5	CNS cancer (astro) SNB-75	0.1
Lung ca. NCI-H146	0.6	CNS cancer (glio) SNB-19	0.1
Lung ca. SHP-77	0.2	CNS cancer (glio) SF-295	0.3
Lung ca. A549	0.0	Brain (Amygdala) Pool	4.0
Lung ca. NCI-H526	0.4	Brain (cerebellum)	2.0
Lung ca. NCI-H23	1.3	Brain (fetal)	0.3
Lung ca. NCI-H460	0.1	Brain (Hippocampus) Pool	2.4
Lung ca. HOP-62	0.2	Cerebral Cortex Pool	2.7
Lung ca. NCI-H522	0.3	Brain (Substantia nigra) Pool	3.5
Liver	0.1	Brain (Thalamus) Pool	4.2
Fetal Liver	0.4	Brain (whole)	1.9
Liver ca. HepG2	0.1	Spinal Cord Pool	3.7
Kidney Pool	1.9	Adrenal Gland	0.4
Fetal Kidney	1.0	Pituitary gland Pool	0.1
Renal ca. 786-0	0.3	Salivary Gland	0.3
Renal ca. A498	0.0	Thyroid (female)	0.2
Renal ca. ACHN	0.2	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.2	Pancreas Pool	0.5

[0898]

TABLE AAD
Panel 4.1D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4481,		Ag4481,
	Run		Run
Tissue Name	195476202	Tissue Name	195476202
Secondary Th1 act	15.7	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	11.4	HUVEC TNF alpha + IFN gamma	0.0
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	12.1	HUVEC IL-11	0.0
Secondary Tr1 rest	11.7	Lung Microvascular EC none	0.0
Primary Th1 act	2.0	Lung Microvascular EC TNFalpha +	0.0
		IL-1beta
Primary Th2 act	20.2	Microvascular Dermal EC none	0.0
Primary Tr1 act	0.0	Microvascular Dermal EC TNFalpha +	0.0
		IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium TNFalpha +	21.8
		IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	0.0
Primary Tr1 rest	0.0	Small airway epithelium TNFalpha +	0.0
		IL-1beta
CD45RA CD4 lymphocyte act	0.0	Coronery artery SMC rest	0.0
CD45RO CD4 lymphocyte act	0.0	Coronery artery SMC TNFalpha + IL-	0.0
		1beta
CD8 lymphocyte act	14.1	Astrocytes rest	23.3
Secondary CD8 lymphocyte rest	0.0	Astrocytes TNFalpha + IL-1beta	0.0
Secondary CD8 lymphocyte act	0.0	KU-812 (Basophil) rest	15.2
CD4 lymphocyte none	0.0	KU-812 (Basophil) PMA/ionomycin	0.0
2ry Th1/Th2/Tr1_anti-CD95 CH11	11.0	CCD1106 (Keratinocytes) none	10.3
LAK cells rest	9.8	CCD1106 (Keratinocytes) TNFalpha +	0.0
		IL-1beta
LAK cells IL-2	46.3	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	23.3	NCI-H292 none	27.9
LAK cells IL-2 + IFN gamma	2.4	NCI-H292 IL-4	0.0
LAK cells IL-2 + IL-18	24.5	NCI-H292 IL-9	6.7
LAK cells PMA/ionomycin	13.6	NCI-H292 IL-13	11.1
NK Cells IL-2 rest	7.8	NCI-H292 IFN gamma	10.7
Two Way MLR 3 day	11.0	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1 beta	0.0
Two Way MLR 7 day	O.0	Lung fibroblast none	0.0
PBMC rest	12.2	Lung fibroblast TNF alpha + IL-1 beta	0.0
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	20.3	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.0
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	0.0
B lymphocytes PWM	0.0	Dermal fibroblast CCD1070 rest	0.0
B lymphocytes CD40L and IL-4	9.6	Dermal fibroblast CCD1070 TNF alpha	10.2
EOL-1 dbcAMP	12.1	Dermal fibroblast CCD1070 IL-1 beta	0.0
EOL-1 dbcAMP PMA/ionomycin	10.8	Dermal fibroblast IFN gamma	0.0
Dendritic cells none	0.0	Dermal fibroblast IL-4	23.2
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	12.1
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	9.3
Macrophages rest	17.4	Lung	20.6
Macrophages LPS	0.0	Thymus	24.0
HUVEC none	0.0	Kidney	100.0
HUVEC starved	0.0

[0899]

TABLE AAE
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4481, Run		Ag4481, Run
Tissue Name	268695127	Tissue Name	268695127
Colon cancer 1	6.9	Bladder cancer NAT 2	0.0
Colon cancer NAT 1	0.0	Bladder cancer NAT 3	0.0
Colon cancer 2	2.4	Bladder cancer NAT 4	0.0
Colon cancer NAT 2	0.0	Prostate adenocarcinoma 1	31.9
Colon cancer 3	16.7	Prostate adenocarcinoma 2	0.0
Colon cancer NAT 3	5.5	Prostate adenocarcinoma 3	22.2
Colon malignant cancer 4	14.6	Prostate adenocarcinoma 4	70.2
Colon normal adjacent tissue 4	2.3	Prostate cancer NAT 5	25.5
Lung cancer 1	8.3	Prostate adenocarcinoma 6	0.0
Lung NAT 1	0.0	Prostate adenocarcinoma 7	1.7
Lung cancer 2	10.4	Prostate adenocarcinoma 8	0.0
Lung NAT 2	15.7	Prostate adenocarcinoma 9	17.1
Squamous cell carcinoma 3	32.5	Prostate cancer NAT 10	5.2
Lung NAT 3	0.0	Kidney cancer 1	11.0
metastatic melanoma 1	35.1	KidneyNAT 1	10.3
Melanoma 2	2.2	Kidney cancer 2	66.9
Melanoma 3	0.0	Kidney NAT 2	14.5
metastatic melanoma 4	67.4	Kidney cancer 3	36.3
metastatic melanoma 5	100.0	Kidney NAT 3	21.9
Bladder cancer 1	2.4	Kidney cancer 4	21.8
Bladder cancer NAT 1	0.0	Kidney NAT 4	8.6
Bladder cancer 2	15.8

[0900] CNS_neurodegeneration_v1.0 Summary: Ag4481 This expression profile confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.

[0901] General_screening_panel_v1.4 Summary: Ag4481 This gene is most highly expressed in fetal heart (CT=26.7). In addition, high levels of expression are seen in skeletal muscle and cell lines derived from colon cancer and lung cancer. This gene is homologous to mysosin, a motor protein involved in cytokinesis, vesicular transport, and cellular locomotion. This characterization is consistent with the prominent expression in heart and muscle. Thus, expression of this gene could be used to differentiate between fetal and adult heart tissue (CT=29.7), to differentiate between the colon and lung cancer cell lines and other samples on this panel, and as a marker of these cancers.

[0902] In addition to high to moderate levels of expression in heart and skeletal muscle, low but significant levels of expression are seen in adipose, fetal liver, pancreas and adrenal. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0903] This gene is also expressed at low to moderate levels in all regions of the CNS examined, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0904] Panel 4.1D Summary: Ag4481 This gene is only expressed at detectable levels in the kidney (CT=34). Thus, expression of this gene could be used to differentiate the kidney derived sample from other samples on this panel and as a marker of kidney tissue. In addition, therapeutic targeting of the expression or function of this gene may modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.

[0905] general oncology screening panel_v—2.4 Summary: Ag4481 Highest expression of this gene is seen in metastatic melanoma (CT=32.5). Low but significant levels of expression are also seen in squamous cell carcinoma, prostate and kidney cancer.

[0906] AB. CG116270-01: Endo-alpha-D-Mannosidase Like

[0907] Expression of gene CG116270-01 was assessed using the primer-probe sets Ag1195, Ag1205, Ag1606 and Ag4491, described in Tables ABA, ABB, ABC and ABD. Results of the RTQ-PCR runs are shown in Tables ABE, ABF, ABG, ABH, ABI, ABJ, ABK, ABL and ABM.

TABLE ABA
Probe Name Ag1195
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tacacctactttgcctccaatg-3′	22	655	259
Probe	TET-5′-cctttggttcttcccatcagaactgg-3′-TAMRA	26	683	260
Reverse	5′-gttggcatcacaaaagttcttc-3′	22	717	261

[0908]

TABLE ABB
Probe Name Ag1205
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tacacctactttgcctccaatg-3′	22	655	262
Probe	TET-5′-cctttggttcttcccatcagaactgg-3′-TAMRA	26	683	263
Reverse	5′-gttggcatcacaaaagttcttc-3′	22	717	264

[0909]

TABLE ABC
Probe Name Ag1606
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tacacctactttgcctccaatg-3′	22	655	265
Probe	TET-5′-cctttggttcttcccatcagaactgg-3′-TAMRA	26	683	266
Reverse	5′-gttggcatcacaaaagttcttc-3′	22	717	267

[0910]

TABLE ABD
Probe Name Ag4491
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tggtgcattttaccgctataa-3′	21	438	268
Probe	TET-5′-tgggcaagagcctcccactcttttat-3′-TAMRA	26	467	269
Reverse	5′-aggggacgtcaggtatgagt-3′	20	500	270

[0911]

TABLE ABE
CNS neurodegeneration v1.0
		Rel.	Rel.
		Exp. (%)	Exp. (%)
		Ag1195,	Ag1606,
		Run	Run
	Tissue Name	206992278	207567960
	AD 1 Hippo	23.5	24.7
	AD 2 Hippo	52.1	31.0
	AD 3 Hippo	15.1	18.3
	AD 4 Hippo	28.1	21.9
	AD 5 hippo	100.0	94.6
	AD 6 Hippo	53.2	65.5
	Control 2 Hippo	67.8	65.5
	Control 4 Hippo	13.6	13.8
	Control (Path) 3 Hippo	8.1	11.0
	AD 1 Temporal Ctx	18.9	19.9
	AD 2 Temporal Ctx	59.9	53.2
	AD 3 Temporal Ctx	11.5	13.3
	AD 4 Temporal Ctx	37.1	35.1
	AD 5 Inf Temporal Ctx	90.8	100.0
	AD 5 Sup Temporal Ctx	61.6	60.7
	AD 6 Inf Temporal Ctx	39.2	42.6
	AD 6 Sup Temporal Ctx	43.2	43.8
	Control 1 Temporal Ctx	10.0	8.4
	Control 2 Temporal Ctx	56.3	61.1
	Control 3 Temporal Ctx	31.2	37.4
	Control 4 Temporal Ctx	11.7	17.7
	Control (Path) 1	84.7	90.8
	Temporal Ctx
	Control (Path) 2	60.3	63.7
	Temporal Ctx
	Control (Path) 3	10.0	8.5
	Temporal Ctx
	Control (Path) 4	52.9	50.3
	Temporal Ctx
	AD 1 Occipital Ctx	20.9	28.9
	AD 2 Occipital Ctx	0.0	0.0
	(Missing)
	AD 3 Occipital Ctx	7.7	9.1
	AD 4 Occipital Ctx	30.1	31.2
	AD 5 Occipital Ctx	19.5	78.5
	AD 6 Occipital Ctx	85.9	15.9
	Control 1 Occipital Ctx	5.9	9.7
	Control 2 Occipital Ctx	81.8	72.7
	Control 3 Occipital Ctx	27.4	37.4
	Control 4 Occipital Ctx	10.8	9.9
	Control (Path) 1	95.9	95.9
	Occipital Ctx
	Control (Path) 2	13.5	19.3
	Occipital Ctx
	Control (Path) 3	5.5	3.1
	Occipital Ctx
	Control (Path) 4	27.5	30.4
	Occipital Ctx
	Control 1 Parietal Ctx	11.4	11.1
	Control 2 Parietal Ctx	56.3	52.1
	Control 3 Parietal Ctx	33.9	35.4
	Control (Path) 1	94.0	99.3
	Parietal Ctx
	Control (Path) 2	28.3	35.4
	Parietal Ctx
	Control (Path) 3	6.6	8.5
	Parietal Ctx
	Control (Path) 4	56.6	71.2
	Parietal Ctx

[0912]

TABLE ABF
General_screening_panel_v1.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4491,		Ag4491,
	Run		Run
Tissue Name	218341381	Tissue Name	218341381
Adipose	0.6	Renal ca. TK-10	54.7
Melanoma* Hs688(A).T	1.0	Bladder	6.5
Melanoma* Hs688(B).T	1.3	Gastric ca. (liver met.) NCI-N87	59.5
Melanoma* M14	53.2	Gastric ca. KATO III	32.8
Melanoma* LOXIMVI	12.3	Colon ca. SW-948	8.1
Melanoma* SK-MEL-5	30.8	Colon ca. SW480	10.3
Squamous Cell Carcinoma SCC-	3.8	Colon ca.* (SW480 met) SW620	15.7
4
Testis Pool	2.5	Colon ca. HT29	12.8
Prostate ca.* (bone met) PC-3	28.9	Colon ca. HCT-116	43.2
Prostate Pool	2.2	Colon ca. CaCo-2	51.8
Placenta	0.9	Colon cancer tissue	9.5
Uterus Pool	0.5	Colon ca. SW1116	11.4
Ovarian ca. OVCAR-3	4.1	Colon ca. Colo-205	0.8
Ovarian ca. SK-OV-3	52.1	Colon ca. SW-48	7.6
Ovarian ca. OVCAR-4	2.0	Colon Pool	1.7
Ovarian ca. OVCAR-5	34.2	Small Intestine Pool	2.0
Ovarian ca. IGROV-1	9.2	Stomach Pool	1.2
Ovarian ca. OVCAR-8	7.5	Bone Marrow Pool	1.1
Ovary	1.8	Fetal Heart	0.8
Breast ca. MCF-7	35.6	Heart Pool	0.6
Breast ca. MDA-MB-231	23.7	Lymph Node Pool	3.4
Breast ca. BT 549	2.3	Fetal Skeletal Muscle	0.8
Breast ca. T47D	70.7	Skeletal Muscle Pool	3.9
Breast ca. MDA-N	20.0	Spleen Pool	2.3
Breast Pool	2.4	Thymus Pool	3.8
Trachea	3.2	CNS cancer (glio/astro) U87-MG	4.2
Lung	0.2	CNS cancer (glio/astro) U-118-MG	39.2
Fetal Lung	2.7	CNS cancer (neuro;met) SK-N-AS	8.6
Lung ca. NCI-N417	35.4	CNS cancer (astro) SF-539	12.9
Lung ca. LX-1	13.9	CNS cancer (astro) SNB-75	24.8
Lung ca. NCI-H146	15.4	CNS cancer (glio) SNB-19	16.3
Lung ca. SHP-77	84.1	CNS cancer (glio) SF-295	35.1
Lung ca. A549	18.2	Brain (Amygdala) Pool	12.0
Lung ca. NCI-H526	100.0	Brain (cerebellum)	54.0
Lung ca. NCI-H23	26.6	Brain (fetal)	60.3
Lung ca. NCI-H460	3.7	Brain (Hippocampus) Pool	16.3
Lung ca. HOP-62	1.8	Cerebral Cortex Pool	20.7
Lung ca. NCI-H522	37.4	Brain (Substantia nigra) Pool	16.2
Liver	2.0	Brain (Thalamus) Pool	24.7
Fetal Liver	2.8	Brain (whole)	30.4
Liver ca. HepG2	15.6	Spinal Cord Pool	7.8
Kidney Pool	2.8	Adrenal Gland	8.7
Fetal Kidney	3.4	Pituitary gland Pool	8.6
Renal ca. 786-0	27.2	Salivary Gland	2.7
Renal ca. A498	1.1	Thyroid (female)	1.8
Renal ca. ACHN	16.7	Pancreatic ca. CAPAN2	43.8
Renal ca. UO-31	17.0	Pancreas Pool	6.6

[0913]

TABLE ABG
Panel 1.2
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag1195,		Ag1195,
	Run		Run
Tissue Name	129140457	Tissue Name	129140457
Endothelial cells	0.3	Renal ca. 786-0	3.2
Heart (Fetal)	5.3	Renal ca. A498	0.0
Pancreas	1.6	Renal ca. RXF 393	1.2
Pancreatic ca. CAPAN 2	24.1	Renal ca. ACHN	8.0
Adrenal Gland	20.4	Renal ca. UO-31	2.3
Thyroid	0.6	Renal ca. TK-10	8.5
Salivary gland	5.6	Liver	6.6
Pituitary gland	11.0	Liver (fetal)	1.7
Brain (fetal)	30.6	Liver ca. (hepatoblast) HepG2	7.9
Brain (whole)	23.0	Lung	1.5
Brain (amygdala)	31.4	Lung (fetal)	1.0
Brain (cerebellum)	20.3	Lung ca. (small cell) LX-1	1.6
Brain (hippocampus)	47.6	Lung ca. (small cell) NCI-H69	5.1
Brain (thalamus)	11.7	Lung ca. (s.cell var.) SHP-77	10.4
Cerebral Cortex	100.0	Lung ca. (large cell)NCI-H460	23.3
Spinal cord	7.6	Lung ca. (non-sm. cell) A549	6.0
glio/astro U87-MG	1.7	Lung ca. (non-s.cell) NCI-H23	6.3
glio/astro U-118-MG	9.2	Lung ca. (non-s.cell) HOP-62	2.0
astrocytoma SW1783	0.5	Lung ca. (non-s.cl) NCI-H522	42.0
neuro*; met SK-N-AS	2.3	Lung ca. (squam.) SW 900	3.7
astrocytoma SF-539	1.4	Lung ca. (squam.) NCI-H596	8.7
astrocytoma SNB-75	2.0	Mammary gland	8.7
glioma SNB-19	8.4	Breast ca.* (pl.ef) MCF-7	8.5
glioma U251	3.0	Breast ca.* (pl.ef) MDA-MB-231	1.4
glioma SF-295	24.0	Breast ca.* (pl.ef) T47D	3.8
Heart	4.4	Breast ca. BT-549	0.7
Skeletal Muscle	2.7	Breast ca. MDA-N	3.6
Bone marrow	0.7	Ovary	2.7
Thymus	0.6	Ovarian ca. OVCAR-3	1.6
Spleen	1.1	Ovarian ca. OVCAR-4	1.1
Lymph node	5.0	Ovarian ca. OVCAR-5	10.4
Colorectal Tissue	10.6	Ovarian ca. OVCAR-8	2.0
Stomach	22.5	Ovarian ca. IGROV-1	1.9
Small Intestine	4.7	Ovarian ca. (ascites) SK-OV-3	17.1
Colon ca. SW480	0.2	Uterus	1.3
Colon ca.* SW620 (SW480 met)	1.9	Placenta	1.8
Colon ca. HT29	1.1	Prostate	9.3
Colon ca. HCT-116	3.0	Prostate ca.* (bone met) PC-3	45.4
Colon ca. CaCo-2	6.6	Testis	10.3
Colon ca. Tissue (ODO3866)	5.5	Melanoma Hs688(A).T	0.1
Colon ca. HCC-2998	6.2	Melanoma* (met) Hs688(B).T	0.0
Gastric ca.* (liver met) NCI-N87	11.3	Melanoma UACC-62	27.7
Bladder	12.4	Melanoma M14	27.0
Trachea	2.6	Melanoma LOX IMVI	8.7
Kidney	1.4	Melanoma* (met) SK-MEL-5	19.6
Kidney (fetal)	4.3

[0914]

TABLE ABH
Panel 1.3D
	Rel. Exp. (%)	Rel. Exp. (%)	Rel. Exp. (%)
	Ag1205,	Ag1606,	Ag1606,
	Run	Run	Run
Tissue Name	165519985	146863593	147785167
Liver	38.7	35.6	19.6
adenocarcinoma
Pancreas	10.4	5.7	2.6
Pancreatic ca.	33.9	17.1	7.2
CAPAN 2
Adrenal gland	4.2	3.3	2.7
Thyroid	3.3	3.8	2.4
Salivary gland	4.0	1.9	2.4
Pituitary gland	40.1	26.6	18.4
Brain (fetal)	89.5	21.0	17.3
Brain (whole)	97.9	28.1	18.9
Brain (amygdala)	74.2	47.6	18.8
Brain	66.9	9.9	7.0
(cerebellum)
Brain	66.9	52.5	22.8
(hippocampus)
Brain (substantia	27.4	7.5	3.6
nigra)
Brain (thalamus)	100.0	25.5	21.5
Cerebral Cortex	88.3	100.0	100.0
Spinal cord	23.0	10.6	4.5
glio/astro U87-	2.9	5.1	2.4
MG
glio/astro U-118-	42.0	40.1	38.2
MG
astrocytoma	1.1	1.4	1.0
SW1783
neuro*; met	4.4	9.1	7.3
SK-N-AS
astrocytoma SF-	14.5	17.3	4.3
539
astrocytoma	33.4	45.1	28.7
SNB-75
glioma SNB-19	38.4	14.0	21.9
glioma U251	52.1	16.0	10.6
glioma SF-295	11.6	21.6	15.2
Heart (fetal)	2.0	10.9	9.7
Heart	1.3	1.1	0.9
Skeletal muscle	11.0	15.8	11.3
(fetal)
Skeletal muscle	15.7	3.0	1.0
Bone marrow	1.1	0.6	0.3
Thymus	1.1	0.9	1.0
Spleen	2.8	5.2	1.8
Lymph node	4.7	4.1	2.4
Colorectal	11.4	15.8	11.3
Stomach	12.8	8.5	5.5
Small intestine	12.9	5.2	3.9
Colon ca. SW480	4.2	12.9	7.7
Colon ca.*	9.0	9.9	7.4
SW620 (SW480 met)
Colon ca. HT29	5.9	9.9	10.2
Colon ca. HCT-	12.5	13.6	10.3
116
Colon ca. CaCo-2	21.5	32.5	27.0
Colon ca.	11.6	10.5	11.9
tissue(ODO3866)
Colon ca. HCC-	23.7	36.3	21.6
2998
Gastric ca.*	55.1	58.6	44.8
(liver met)
NCI-N87
Bladder	3.4	5.0	1.7
Trachea	4.6	3.9	2.9
Kidney	7.3	1.8	0.7
Kidney	0.5	1.0	1.2
(fetal)
Renal ca.	22.5	20.6	11.0
786-0
Renal ca.	6.8	7.2	3.7
A498
Renal ca.	13.6	5.1	5.8
RXF 393
Renal ca.	9.7	23.0	21.9
ACHN
Renal ca.	22.2	18.0	15.8
UO-31
Renal ca.	21.9	38.4	14.2
TK-10
Liver	2.5	2.7	1.3
Liver (fetal)	1.2	1.2	1.0
Liver ca.	19.2	29.7	17.3
(hepatoblast)
HepG2
Lung	0.4	2.3	0.7
Lung (fetal)	0.5	1.4	1.3
Lung ca.	9.2	10.2	8.8
(small cell)
LX-1
Lung ca.	7.6	52.9	39.5
(small cell)
NCI-H69
Lung ca.	59.0	66.9	59.0
(s. cell var.)
SHP-77
Lung ca.	10.4	2.8	4.1
(large
cell) NCI-
H460
Lung ca.	5.8	13.4	6.4
(non-sm. cell)
A549
Lung ca.	12.6	28.1	18.4
(non-s. cell)
NCI-H23
Lung ca.	4.0	1.2	2.2
(non-s. cell)
HOP-62
Lung ca.	15.1	22.8	17.3
(non-s. cl)
NCI-H522
Lung ca.	14.7	11.1	9.3
(squam.) SW
900
Lung ca.	32.1	24.1	17.2
(squam.)
NCI-H596
Mammary	10.7	13.3	9.7
gland
Breast ca.*	34.4	33.7	18.8
(pl. ef) MCF-
7
Breast ca.*	25.5	28.7	16.0
(pl. ef) MDA-
MB-231
Breast ca.*	10.9	11.6	8.3
(pl. ef) T47D
Breast ca.	2.2	4.1	2.6
BT-549
Breast ca.	6.5	31.9	20.9
MDA-N
Ovary	1.6	5.6	4.7
Ovarian ca.	5.6	4.1	3.0
OVCAR-3
Ovarian ca.	0.9	0.0	0.6
OVCAR-4
Ovarian ca.	20.4	21.8	16.8
OVCAR-5
Ovarian ca.	5.3	22.7	8.1
OVCAR-8
Ovarian ca.	2.0	2.1	1.3
IGROV-1
Ovarian ca.*	19.9	32.5	19.3
(ascites) SK-
OV-3
Uterus	4.2	1.8	2.0
Placenta	1.6	2.0	2.9
Prostate	3.4	7.0	2.7
Prostate ca.*	7.9	19.1	8.0
(bone met)PC-3
Testis	7.9	8.4	5.0
Melanoma	0.0	4.1	1.1
Hs688(A).T
Melanoma*	1.2	5.0	4.0
(met)
Hs688(B).T
Melanoma	41.8	9.6	5.7
UACC-62
Melanoma	84.7	17.0	8.8
M14
Melanoma	4.2	4.2	2.4
LOX IMVI
Melanoma*	10.7	13.1	5.8
(met) SK-
MEL-5
Adipose	4.0	0.6	1.0

[0915]

TABLE ABI
Panel 2D
		Rel. Exp. (%)	Rel. Exp. (%)
		Ag1606,	Ag1606,
		Run	Run
	Tissue Name	147317894	147785168
	Normal Colon	19.2	20.9
	CC Well to Mod	6.3	11.6
	Diff (ODO3866)
	CC Margin	3.3	5.4
	(ODO3866)
	CC Gr.2	11.7	12.4
	rectosigmoid
	(ODO3868)
	CC Margin	0.9	2.6
	(ODO3868)
	CC Mod Diff	17.9	20.2
	(ODO3920)
	CC Margin	5.5	4.7
	(ODO3920)
	CC Gr.2 ascend	17.3	24.7
	colon
	(ODO3921)
	CC Margin	5.3	4.8
	(OD03921)
	CC from Partial	1.9	3.6
	Hepatectomy
	(ODO4309)Mets
	Liver Margin	6.5	8.0
	(ODO4309)
	Colon mets to	12.8	17.3
	lung (OD04451-01)
	Lung Margin	3.0	3.7
	(OD04451-02)
	Normal Prostate	10.4	11.7
	6546-1
	Prostate Cancer	52.1	50.7
	(OD04410)
	Prostate Margin	18.8	20.0
	(OD04410)
	Prostate Cancer	9.6	11.3
	(OD04720-01)
	Prostate Margin	11.1	10.8
	(OD04720-02)
	Normal Lung	7.1	6.8
	061010
	Lung Met to	12.9	12.0
	Muscle
	(ODO4286)
	Muscle Margin	2.9	3.6
	(ODO4286)
	Lung Malignant	11.9	11.4
	Cancer
	(OD03126)
	Lung Margin	9.3	10.5
	(OD03126)
	Lung Cancer	4.3	6.0
	(OD04404)
	Lung Margin	5.4	7.7
	(OD04404)
	Lung Cancer	2.5	4.2
	(OD04565)
	Lung Margin	4.8	5.9
	(OD04565)
	Lung Cancer	11.5	11.0
	(OD04237-01)
	Lung Margin	5.0	5.8
	(OD04237-02)
	Ocular Mel Met	6.5	11.5
	to Liver
	(ODO4310)
	Liver Margin	3.9	8.3
	(ODO4310)
	Melanoma Mets	6.4	10.5
	to Lung
	(OD04321)
	Lung Margin	5.4	7.3
	(OD04321)
	Normal Kidney	9.3	12.0
	Kidney Ca,	25.3	31.6
	Nuclear grade 2
	(OD04338)
	Kidney Margin	9.9	0.1
	(OD04338)
	Kidney Ca	2.2	0.9
	Nuclear grade
	1/2 (OD04339)
	Kidney Margin	8.1	12.5
	(OD04339)
	Kidney Ca, Clear	2.7	3.2
	cell type
	(OD04340)
	Kidney Margin	8.1	9.0
	(OD04340)
	Kidney Ca,	11.4	12.8
	Nuclear grade 3
	(OD04348)
	Kidney Margin	9.1	8.1
	(OD04348)
	Kidney Cancer	7.5	8.0
	(OD04622-01)
	Kidney Margin	3.6	3.2
	(OD04622-03)
	Kidney Cancer	97.9	43.2
	(OD04450-01)
	Kidney Margin	6.4	9.7
	(OD04450-03)
	Kidney Cancer	27.7	34.2
	8120607
	Kidney Margin	6.0	3.3
	8120608
	Kidney Cancer	4.6	6.6
	8120613
	Kidney Margin	9.2	6.3
	8120614
	Kidney Cancer	51.1	52.1
	9010320
	Kidney Margin	4.9	7.2
	9010321
	Normal Uterus	0.6	0.7
	Uterus Cancer	2.3	3.7
	064011
	Normal Thyroid	4.6	6.8
	Thyroid Cancer	13.1	17.6
	064010
	Thyroid Cancer	24.1	21.0
	A302152
	Thyroid Margin	2.7	2.7
	A302153
	Normal Breast	5.5	6.3
	Breast Cancer	14.7	20.4
	(OD04566)
	Breast Cancer	95.9	100.0
	(OD04590-01)
	Breast Cancer	70.2	74.2
	Mets
	(OD04590-03)
	Breast Cancer	100.0	94.0
	Metastasis
	(OD04655-05)
	Breast Cancer	7.7	10.1
	064006
	Breast Cancer	36.9	51.1
	1024
	Breast Cancer	18.0	21.9
	9100266
	Breast Margin	6.0	6.5
	9100265
	Breast Cancer	43.8	52.1
	A209073
	Breast Margin	12.4	10.7
	A209073
	Normal Liver	5.0	10.2
	Liver Cancer	12.1	12.9
	064003
	Liver Cancer	6.2	8.6
	1025
	Liver Cancer	29.1	32.3
	1026
	Liver Cancer	6.5	7.3
	6004-T
	Liver Tissue	7.5	7.9
	6004-N
	Liver Cancer	29.3	33.2
	6005-T
	Liver Tissue	5.4	5.0
	6005-N
	Normal	11.4	12.8
	Bladder
	Bladder	6.7	12.9
	Cancer 1023
	Bladder	1.8	2.3
	Cancer
	A302173
	Bladder	20.7	26.4
	Cancer
	(OD04718-01)
	Bladder	1.1	3.0
	Normal
	Adjacent
	(OD04718-03)
	Normal Ovary	2.1	1.5
	Ovarian	12.0	11.3
	Cancer
	064008
	Ovarian	90.1	97.3
	Cancer
	(OD04768-07)
	Ovary Margin	0.3	0.9
	(OD04768-08)
	Normal	5.3	4.5
	Stomach
	Gastric Cancer	2.7	2.3
	9060358
	Stomach	5.1	8.4
	Margin
	9060359
	Gastric Cancer	29.5	29.3
	9060395
	Stomach	17.2	17.3
	Margin
	9060394
	Gastric Cancer	42.6	48.0
	9060397
	Stomach	4.8	3.6
	Margin
	9060396
	Gastric Cancer	12.9	12.0
	064005

[0916]

TABLE ABJ
Panel 3D
		Rel.	Rel.
		Exp. (%)	Exp. (%)
		Ag1205,	Ag1606,
		Run	Run
	Tissue Name	164038912	182113408
	Daoy-	0.5	0.3
	Medulloblastoma
	TE671-	1.7	1.0
	Medulloblastoma
	D283 Med-	2.4	2.0
	Medulloblastoma
	PFSK-1-Primitive	4.0	3.0
	Neuroectodermal
	XF-498- CNS	3.1	2.4
	SNB-78-Glioma	5.8	2.7
	SF-268-	3.5	3.0
	Glioblastoma
	T98G-	5.1	3.3
	Glioblastoma
	SK-N-SH-Neuroblastoma	3.6	1.8
	(metastasis)
	SF-295-	2.7	1.6
	Glioblastoma
	Cerebellum	4.2	2.5
	Cerebellum	5.1	2.9
	NCI-H292-	14.5	10.6
	Mucoepidermoid
	lung carcinoma
	DMS-114- Small	7.1	5.1
	cell lung cancer
	DMS-79- Small	100.0	100.0
	cell lung cancer
	NCI-H146- Small	8.1	4.2
	cell lung cancer
	NCI-H526- Small	64.6	38.7
	cell lung cancer
	NCI-N417- Small cell	21.0	9.8
	lung cancer
	NCI-H82- Small	11.7	5.4
	cell lung cancer
	NCI-H157-	2.5	1.2
	Squamous cell
	lung cancer
	(metastasis)
	NCI-H1155-	25.7	15.0
	Large cell lung
	cancer
	NCI-H1299-	3.6	1.9
	Large cell lung
	cancer
	NCI-H727- Lung	14.7	8.0
	carcinoid
	NCI-UMC-11-	21.8	9.2
	Lung carcinoid
	LX-1- Small cell	1.6	1.1
	lung cancer
	Colo-205- Colon	0.4	0.1
	cancer
	KM12- Colon	7.0	4.2
	cancer
	KM20L2- Colon	1.5	0.6
	cancer
	NCI-H716- Colon	23.7	15.9
	cancer
	SW-48- Colon	3.1	1.7
	adenocarcinoma
	SW1116- Colon	2.6	2.0
	adenocarcinoma
	LS 174T- Colon	3.7	1.6
	adenocarcinoma
	SW-948- Colon	0.8	0.4
	adenocarcinoma
	SW-480- Colon	1.2	0.3
	adenocarcinoma
	NCI-SNU-5-	1.5	0.6
	Gastric carcinoma
	KATO III- Gastric	11.1	9.0
	carcinoma
	NCI-SNU-16-	3.0	1.3
	Gastric carcinoma
	NCI-SNU-1-	11.7	8.3
	Gastric carcinoma
	RF-1- Gastric	6.5	2.3
	adenocarcinoma
	RF-48- Gastric	5.3	3.0
	adenocarcinoma
	MKN-45- Gastric	12.7	7.4
	carcinoma
	NCI-N87- Gastric	8.2	3.7
	carcinoma
	OVCAR-5-	1.2	0.6
	Ovarian
	carcinoma
	RL95-2- Uterine	4.1	1.8
	carcinoma
	HelaS3- Cervical	5.8	2.4
	adenocarcinoma
	Ca Ski- Cervical	14.7	4.7
	epidermoid
	carcinoma
	(metastasis)
	ES-2- Ovarian clear	0.5	0.0
	cell carcinoma
	Ramos- Stimulated	1.1	0.2
	with PMA/ionomycin
	6h
	Ramos- Stimulated	1.6	0.8
	with PMA/ionomycin
	14h
	MEG-01- Chronic	3.4	1.7
	myelogenous
	leukemia
	(megokaryoblast)
	Raji- Burkitt's	2.5	0.9
	lymphoma
	Daudi- Burkitt's	6.2	2.5
	lymphoma
	U266- B-cell	7.2	2.7
	plasmacytoma
	CA46- Burkitt's	3.5	0.6
	lymphoma
	RL- non-Hodgkin's	1.5	1.1
	B-cell lymphoma
	JM1- pre-B-cell	3.9	1.6
	lymphoma
	Jurkat- T cell	2.5	0.7
	leukemia
	TF-1-	1.2	0.2
	Erythroleukemia
	HUT 78- T-cell	5.3	1.9
	lymphoma
	U937-Histiocytic	11.5	4.4
	lymphoma
	KU-812-	0.3	0.2
	Myelogenous
	leukemia
	769-P- Clear cell	0.8	0.5
	renal carcinoma
	Caki-2- Clear cell	2.9	1.2
	renal carcinoma
	SW 839- Clear cell	1.6	0.5
	renal carcinoma
	G401- Wilms' tumor	2.9	1.8
	Hs766T- Pancreatic	1.9	0.8
	carcinoma (LN
	metastasis)
	CAPAN-1-	5.4	1.8
	Pancreatic
	adenocarcinoma
	(liver metastasis)
	SU86.86- Pancreatic	2.8	0.7
	carcinoma (liver
	metastasis)
	BxPC-3- Pancreatic	2.7	1.4
	adenocarcinoma
	HP AC- Pancreatic	3.6	2.1
	adenocarcinoma
	MIA PaCa-2-	1.0	0.7
	Pancreatic carcinoma
	CFPAC-1- Pancreatic	3.2	1.9
	ductal
	adenocarcinoma
	PANC-1- Pancreatic	6.3	5.0
	epithelioid ductal
	carcinoma
	T24- Bladder	4.8	2.6
	carcinma (transitional
	cell)
	5637- Bladder	2.8	1.8
	carcinoma
	HT-1197- Bladder	5.5	2.1
	carcinoma
	UM-UC-3- Bladder	2.1	1.1
	carcinma (transitional
	cell)
	A204-	3.1	1.7
	Rhabdomyosarcoma
	HT-1080-	1.8	1.2
	Fibrosarcoma
	MG-63-	0.8	0.3
	Osteosarcoma
	SK-LMS-1-	6.2	3.5
	Leiomyosarcoma
	(vulva)
	SJRH30-	3.4	1.1
	Rhabdomyosarcoma
	(met to bone marrow)
	A431-Epidermoid	1.1	0.6
	carcinoma
	WM266-4-	7.7	3.9
	Melanoma
	DU 145- Prostate	0.0	0.1
	carcinoma (brain
	metastasis)
	MDA-MB-468-Breast	7.1	5.8
	adenocarcinoma
	SCC-4- Squamous	0.0	0.0
	cell carcinoma of
	tongue
	SCC-9- Squamous	0.0	0.1
	cell carcinoma of
	tongue
	SCC-15- Squamous	0.1	0.0
	cell carcinoma of
	tongue
	CAL 27- Squamous	2.5	1.1
	cell carcinoma of
	tongue

[0917]

TABLE ABK
Panel 4D
	Rel. Exp. (%)	Rel. Exp. (%)	Rel. Exp. (%)	Rel. Exp. (%)
	Ag1195, Run	Ag1205, Run	Ag1205, Run	Ag1606, Run
Tissue Name	139026286	140393965	144170671	147785204
Secondary Th1 act	2.0	5.2	4.2	1.2
Secondary Th2 act	3.1	5.3	5.0	3.2
Secondary Tr1 act	4.7	3.4	5.6	4.9
Secondary Th1 rest	0.2	0.1	0.3	0.4
Secondary Th2 rest	0.5	0.0	0.4	0.2
Secondary Tr1 rest	0.4	0.0	0.3	0.7
Primary Th1 act	3.7	2.9	4.2	3.0
Primary Th2 act	1.6	1.9	3.6	2.0
Primary Tr1 act	7.3	2.1	5.5	4.3
Primary Th1 rest	2.1	0.1	1.6	2.2
Primary Th2 rest	0.3	0.0	0.5	0.9
Primary Tr1 rest	1.5	0.4	1.6	2.0
CD45RA CD4	1.3	2.9	1.2	1.8
lymphocyte act
CD45RO CD4	3.0	4.1	2.8	2.4
lymphocyte act
CD8 lymphocyte act	3.8	4.7	5.3	6.1
Secondary CD8	4.7	3.9	3.3	2.6
lymphocyte rest
Secondary CD8	3.4	1.3	5.6	2.6
lymphocyte act
CD4 lymphocyte none	0.6	0.3	0.3	0.4
2ry Th1/Th2/Tr1_anti-	0.8	0.4	0.9	0.5
CD95 CH11
LAK cells rest	2.4	1.7	4.3	2.6
LAK cells IL-2	4.8	1.5	5.7	3.8
LAK cells IL-2 + IL-12	5.5	2.8	6.1	4.7
LAK cells IL-2 + IFN	4.8	2.9	6.5	6.2
gamma
LAK cells IL-2 + IL-18	4.6	1.0	6.8	5.3
LAK cells	1.2	2.4	2.5	2.0
PMA/ionomycin
NK Cells IL-2 rest	1.5	4.0	2.4	4.1
Two Way MLR 3 day	4.5	6.2	4.9	4.2
Two Way MLR 5 day	2.7	2.5	4.6	3.3
Two Way MLR 7 day	1.1	1.9	1.3	0.7
PBMC rest	0.5	0.8	0.8	0.5
PBMC PWM	12.1	6.0	11.6	9.5
PBMC PHA-L	4.2	1.7	5.6	2.2
Ramos (B cell) none	38.2	19.6	53.2	20.0
Ramos (B cell)	45.1	15.5	57.8	48.0
ionomycin
B lymphocytes PWM	4.6	1.3	4.9	7.9
B lymphocytes CD40L	2.7	0.5	2.1	2.1
and IL-4
EOL-1 dbcAMP	12.1	20.9	21.0	19.3
EOL-1 dbcAMP	9.2	9.0	7.3	6.8
PMA/ionomycin
Dendritic cells none	2.8	3.5	4.6	4.2
Dendritic cells LPS	1.8	1.9	2.6	1.9
Dendritic cells anti-	5.7	4.7	6.1	7.4
CD40
Monocytes rest	0.5	0.3	0.4	1.0
Monocytes LPS	3.5	3.4	6.1	5.6
Macrophages rest	12.0	5.1	12.9	8.7
Macrophages LPS	1.9	1.0	2.4	1.7
HUVEC none	0.2	0.2	0.3	1.1
HUVEC starved	1.2	0.5	0.9	2.0
HUVEC IL-1beta	0.3	0.1	0.3	0.2
HUVEC IFN gamma	0.6	1.1	2.0	1.6
HUVEC TNF alpha +	0.1	0.3	0.2	0.7
IFN gamma
HUVEC TNF alpha +	0.4	0.7	0.9	0.6
IL4
HUVEC IL-11	1.2	1.1	0.5	0.8
Lung Microvascular EC	2.4	2.5	3.1	3.3
none
Lung Microvascular EC	1.1	0.4	1.7	2.4
TNFalpha + IL-1beta
Microvascular Dermal	0.9	0.8	2.5	0.8
EC none
Microsvasular Dermal	1.0	0.4	1.2	0.7
EC TNFalpha + IL-
1beta
Bronchial epithelium	0.6	1.1	1.5	0.3
TNFalpha + IL1beta
Small airway	2.2	0.8	4.0	3.3
epithelium none
Small airway	2.9	1.6	4.1	3.6
epithelium TNFalpha +
IL-1beta
Coronery artery SMC	1.2	0.1	1.2	0.2
rest
Coronery artery SMC	0.2	0.2	0.6	0.3
TNFalpha + IL-1beta
Astrocytes rest	0.8	0.7	0.8	0.6
Astrocytes TNFalpha +	0.3	1.3	1.5	1.9
IL-1beta
KU-812 (Basophil) rest	2.6	3.6	1.8	1.8
KU-812 (Basophil)	2.9	2.7	5.6	4.6
PMA/ionomycin
CCD1106	2.8	1.1	3.7	5.3
(Keratinocytes) none
CCD1106	4.1	1.7	7.2	0.4
(Keratinocytes)
TNFalpha + IL-1beta
Liver cirrhosis	1.7	1.7	2.3	2.1
Lupus kidney	2.3	1.2	3.6	0.8
NCI-H292 none	61.6	27.4	74.7	72.2
NCI-H292 IL-4	76.3	38.4	100.0	100.0
NCI-H292 IL-9	100.0	32.8	88.9	98.6
NCI-H292 IL-13	56.6	100.0	79.0	53.6
NCI-H292 IFN gamma	33.0	52.9	47.3	50.0
HPAEC none	0.8	2.0	1.4	1.0
HPAEC TNF alpha +	0.6	0.1	0.7	0.4
IL-1 beta
Lung fibroblast none	0.7	0.5	0.7	0.9
Lung fibroblast TNF	0.2	0.1	0.3	0.3
alpha + IL-1 beta
Lung fibroblast IL-4	1.2	0.6	2.1	0.8
Lung fibroblast IL-9	0.8	0.5	1.1	0.4
Lung fibroblast IL-13	1.7	1.4	2.0	0.9
Lung fibroblast IFN	1.4	0.4	1.1	1.4
gamma
Dermal fibroblast	1.4	0.5	1.3	1.0
CCD1070 rest
Dermal fibroblast	4.0	0.7	5.3	4.4
CCD1070 TNF alpha
Dermal fibroblast	0.6	1.6	0.8	0.7
CCD1070 IL-1 beta
Dermal fibroblast IFN	0.6	0.2	0.0	0.4
gamma
Dermal fibroblast IL-4	1.8	2.3	0.7	1.0
IBD Colitis 2	0.3	0.0	0.5	0.0
IBD Crohn's	0.2	0.6	0.7	0.4
Colon	3.7	2.5	4.1	8.7
Lung	2.9	2.7	3.7	6.5
Thymus	8.0	5.1	11.8	5.3
Kidney	1.4	0.7	0.3	1.1

[0918]

TABLE ABL
Panel CNS_1
	Rel. Exp.		Rel. Exp.
	(%) Ag1195,		(%) Ag1195,
	Run		Run
Tissue Name	171629503	Tissue Name	171629503
BA4 Control	34.6	BA17 PSP	25.7
BA4 Control2	52.5	BA17 PSP2	16.3
BA4	12.5	Sub Nigra Control	25.2
Alzheimer's2
BA4 Parkinson's	43.2	Sub Nigra Control2	20.4
BA4	100.0	Sub Nigra	14.4
Parkinson's2		Alzheimer's2
BA4	27.9	Sub Nigra	32.5
Huntington's		Parkinson's2
BA4	16.5	Sub Nigra	47.3
Huntington's2		Huntington's
BA4 PSP	11.7	Sub Nigra	26.6
		Huntington's2
BA4 PSP2	27.4	Sub Nigra PSP2	4.3
BA4 Depression	24.1	Sub Nigra	3.6
		Depression
BA4	13.1	Sub Nigra	6.9
Depression2		Depression2
BA7 Control	48.0	Glob Palladus	6.2
		Control
BA7 Control2	54.3	Glob Palladus	10.5
		Control2
BA7	7.0	Glob Palladus	10.2
Alzheimer's2		Alzheimer's
BA7 Parkinson's	18.7	Glob Palladus	4.6
		Alzheimer's2
BA7	35.8	Glob Palladus	41.8
Parkinson's2		Parkinson's
BA7	52.5	Glob Palladus	21.5
Huntington's		Parkinson's2
BA7	26.8	Glob Palladus PSP	6.7
Huntington's2
BA7 PSP	30.8	Glob Palladus PSP2	11.7
BA7 PSP2	26.6	Glob Palladus	4.5
		Depression
BA7 Depression	21.3	Temp Pole Control	21.9
BA9 Control	36.3	Temp Pole Control2	35.1
BA9 Control2	90.8	Temp Pole	6.2
		Alzheimer's
BA9 Alzheimer's	6.7	Temp Pole	7.6
		Alzheimer's2
BA9	51.4	Temp Pole	27.5
Alzheimer's2		Parkinson's
BA9 Parkinson's	33.0	Temp Pole	33.0
		Parkinson's2
BA9	38.4	Temp Pole	43.5
Parkinson's2		Huntington's
BA9	57.0	Temp Pole PSP	3.1
Huntington's
BA9	11.3	Temp Pole PSP2	14.8
Huntington's
BA9 PSP	12.1	Temp Pole	7.0
		Depression2
BA9 PSP2	1.2	Cing Gyr Control	40.9
BA9 Depression	14.1	Cing Gyr Control2	42.9
BA9	8.8	Cing Gyr	13.8
Depression2		Alzheimer's
BA17 Control	23.2	Cing Gyr	14.8
		Alzheimer's2
BA17 Control2	47.3	Cing Gyr	17.1
		Parkinson's
BA17	9.2	Cing Gyr	37.6
Alzheimer's2		Parkinson's2
BA17	27.9	Cing Gyr	53.2
Parkinson's		Huntington's
BA17	59.9	Cing Gyr	12.5
Parkinson's2		Huntington's2
BA17	46.7	Cing Gyr PSP	5.6
Huntington's
BA17	7.8	Cing Gyr PSP2	7.9
Huntington's
BA17	11.7	Cing Gyr Depression	6.0
Depression
BA17	34.9	Cing Gyr	8.1
Depression2		Depression2

[0919]

TABLE ABM
general oncology screening panel_v_2.4
	Rel. Exp.		Rel. Exp.
	(%) Ag4491,		(%) Ag4491,
	Run		Run
Tissue Name	260280708	Tissue Name	260280708
Colon cancer 1	20.4	Bladder NAT 2	0.0
Colon NAT 1	8.9	Bladder NAT 3	0.4
Colon cancer 2	13.5	Bladder NAT 4	1.1
Colon NAT 2	9.3	Prostate	8.7
		adenocarcinoma 1
Colon cancer 3	40.6	Prostate	0.7
		adenocarcinoma 2
Colon NAT 3	8.7	Prostate	7.7
		adenocarcinoma 3
Colon malignant	100.0	Prostate	8.4
cancer 4		adenocarcinoma 4
Colon NAT 4	3.5	Prostate NAT 5	0.4
Lung cancer 1	9.6	Prostate	6.0
		adenocarcinoma 6
Lung NAT 1	0.1	Prostate	3.4
		adenocarcinoma 7
Lung cancer 2	13.3	Prostate	0.5
		adenocarcinoma 8
Lung NAT 2	0.3	Prostate	10.9
		adenocarcinoma 9
Squamous cell	41.5	Prostate NAT 10	0.9
carcinoma 3
Lung NAT 3	1.1	Kidney cancer 1	2.3
Metastatic	4.7	Kidney NAT 1	3.4
melanoma 1
Melanoma 2	1.0	Kidney cancer 2	40.9
Melanoma 3	0.2	Kidney NAT 2	9.6
Metastatic	8.8	Kidney cancer 3	3.3
melanoma 4
Metastatic	8.2	Kidney NAT 3	2.6
melanoma 5
Bladder cancer 1	0.2	Kidney cancer 4	7.1
Bladder NAT 1	0.0	Kidney NAT 4	2.1
Bladder cancer 2	2.6

[0920] CNS_neurodegeneration_v1.0 Summary: Ag1195/Ag1606 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. See Panel 1.3D for a discussion of this gene in treatment of central nervous system disorders.

[0921] General_screening_panel_v1.4 Summary: Ag4491 Moderate expression of the CG116270-01 gene occurs predominantly in cancer cell lines, with highest expression in a lung cancer cell line (CT=27.4). Specifically, this gene appears to be expressed at higher levels in colon, gastric, renal, lung, breast, ovarian and pancreatic cancer cell lines when compared to their respective normal tissues. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of these types of cancer.

[0922] In addition, this gene is expressed at moderate levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0923] Among tissues with metabolic or endocrine function, this gene is expressed at low levels in pancreas, adrenal gland, thyroid, pituitary gland, skeletal muscle, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0924] Panel 1.2 Summary: Ag1195 Expression of this gene is highest in cerebral cortex (CT=24.2). Consistent with what is seen in Panel 1.4, expression of this gene is primarily associated with normal brain samples and cancer cell lines. See Panel 1.4 for additional discussion of this gene in human diseases.

[0925] Panel 1.3D Summary: Ag1205/Ag1606 Results from three experiments using the same probe-primer set are in reasonable agreement. Expression of this gene is highest in the brain. Consistent with what is seen in Panel 1.4, expression of this gene is primarily associated with normal brain samples and cancer cell lines. See Panel 1.4 for additional discussion of this gene in human diseases.

[0926] Panel 2.2 Summary: Ag1205 See results for Panel 2D.

[0927] Panel 2D Summary: Ag1606 Results from two experiments using the same probe-primer set are in good agreement. Expression of the CG116270-01 gene is highest in breast cancer samples (CTs=27). Strikingly, expression of this gene is upregulated in 7/8 breast cancer samples when compared to normal breast tissue. In addition, this gene is expressed at higher levels in ovarian tumors and a subset of renal carcinomas, when compared to their respective normal controls. Thus, the expression of this gene could be used as a marker for breast, ovarian and renal cancer. Furthermore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of breast, ovarian, and kidney cancer.

[0928] The CG116270-01 gene encodes a protein with homology to endo-alpha-D-mannosidase, a carbohydrate-processing enzyme. Inhibitors of carbohydrate-processing enzymes have been proposed as novel targets for anticancer therapy as a result of their ability to modify specific carbohydrate structures on secreted and transmembrane glycoproteins [Goss P E, Baker M A, Carver J P, Dennis J W. Clin Cancer Res. September 1995;1(9):935-44, PMID: 9816064]. Oligosaccharide moieties of cell-surface glycoproteins are thought to be involved in recognition events during cancer metastasis and invasion [Roberts J D, Klein J L, Palmantier R, Dhume S T, George M D, Olden K., Cancer Detect Prev. 1998;22(5):455-62, PMID: 9727627]. Swainsonine, an inhibitor of the Golgi alpha-mannosidase II, has been shown to block pulmonary colonization by tumor cells and stimulate components of the immune system. Swainsonine also abrogates much of the toxicity of chemotherapeutic agents and stimulates bone marrow hematopoietic progenitor cells, suggesting additional therapeutic applications. These observations in combination with the expression results presented here are supportive of a potential role for the CG116270-01 gene in cancer and metastasis.

[0929] Panel 3D Summary: Ag1205/Ag1606 Results from two experiments using identical probe-primer sets are in excellent agreement. Expression of the CG116270-01 gene is highest in a small cell lung cancer cell line (CT=25). Interestingly, the highest levels of CG116270-01 gene expression appear to be clustered in the lung cancer cell lines. However, this gene is also expressed at moderate to low levels in the majority of the cancer cell lines in this panel, suggesting that this gene may play a more general role in cancer development.

[0930] Panel 4D Summary: Ag1195/Ag1205/Ag1606 Four experiments using, two different probe-primer sets produced results that are in excellent agreement. Highest expression of the CG116270-01 gene is seen in a cluster of treated and untreated samples derived from the NCI-H292 cell line, a human airway epithelial cell line that produces mucins. Mucus overproduction is an important feature of bronchial asthma and chronic obstructive pulmonary disease samples. The expression of the transcript in the NCI-H292 samples suggests that this transcript may be important in the proliferation or activation of airway epithelium. Therefore, therapeutic modulation of the activity of this gene or its protein product may reduce or eliminate symptoms caused by inflammation in lung epithelia in chronic obstructive pulmonary disease, asthma, allergy, and emphysema.

[0931] This gene is also expressed at lower levels in a wide range of cell types of significance in the immune response in health and disease, including T-cells, B-cells, endothelial cells, macrophages, monocytes, eosinophils, basophils, neutrophils, peripheral blood mononuclear cells, lung and skin epithelial cells, lung and skin fibroblast cells, as well as normal tissues represented by colon, lung, thymus and kidney. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0932] The CG116270-01 gene encodes a protein with homology to endo-alpha-D-mannosidase, a carbohydrate-processing enzyme. Modifications of carbohydrate structures on secreted and transmembrane glycoproteins could affect cell-cell and cell-substratum interactions, including processes such as lymphocyte trafficking, immune cell stimulation, embryogenesis, and cancer metastasi[Goss P E, Baker M A, Carver J P, Dennis J W. Clin Cancer Res. September 1995;1(9):935-44, PMID: 9816064].

[0933] Panel CNS—1 Summary: Ag1195 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. See Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.

[0934] general oncology screening panel_v—2.4 Summary: Ag4491 Expression of this gene is highest in a malignant colon cancer sample (CT=28). Strikingly, expression of the CG116270-01 gene is upregulated in 3/3 lung tumors when compared to the matched normal tissue. This observation is consistent with the results observed in Panels 1.4 and 3D. In addition, expression of this gene is upregulated in a subset of prostate and colon tumors relative to their respective normal controls. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of lung, colon and prostate cancer. See Panel 2D for additional discussion of this gene in cancer and metastasis.

[0935] AC. CG118160-01: Latrophilin 2

[0936] Expression of gene CG118160-01 was assessed using the primer-probe set Ag4492, described in Table ACA. Results of the RTQ-PCR runs are shown in Tables ACB, ACC, ACD and ACE.

TABLE ACA
Probe Name Ag4492
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gcagatgcttcatctttaatgc-3′	22	3967	271
Probe	TET-5′-acaacccagggctggagctccat-3′-TAMRA	23	3995	272
Reverse	5′-aagtggtgcctcgagttctt-3′	20	4022	273

[0937]

TABLE ACB
CNS_neurodegeneration_v1.0
	Rel. Exp.		Rel. Exp.
	(%) Ag4492,		(%) Ag4492,
	Run		Run
Tissue Name	224621654	Tissue Name	224621654
AD 1 Hippo	12.5	Control (Path) 3	10.6
		Temporal Ctx
AD 2 Hippo	25.3	Control (Path) 4	72.7
		Temporal Ctx
AD 3 Hippo	12.0	AD 1 Occipital	35.8
		Ctx
AD 4 Hippo	10.2	AD 2 Occipital	0.0
		Ctx (Missing)
AD 5 hippo	100.0	AD 3 Occipital	13.0
		Ctx
AD 6 Hippo	22.5	AD 4 Occipital	43.2
		Ctx
Control 2 Hippo	24.3	AD 5 Occipital	26.8
		Ctx
Control 4 Hippo	8.4	AD 6 Occipital	56.3
		Ctx
Control (Path) 3 Hippo	8.7	Control 1	8.5
		Occipital Ctx
AD 1 Temporal Ctx	34.6	Control 2	41.8
		Occipital Ctx
AD 2 Temporal Ctx	52.1	Control 3	40.1
		Occipital Ctx
AD 3 Temporal Ctx	19.9	Control 4	8.6
		Occipital Ctx
AD 4 Temporal Ctx	49.0	Control (Path) 1	81.8
		Occipital Ctx
AD 5 Inf Temporal Ctx	88.9	Control (Path) 2	26.2
		Occipital Ctx
AD 5 Sup Temporal Ctx	33.9	Control (Path) 3	7.3
		Occipital Ctx
AD 6 Inf Temporal Ctx	56.3	Control (Path) 4	39.8
		Occipital Ctx
AD 6 Sup Temporal Ctx	0.0	Control 1	12.7
		Parietal Ctx
Control 1 Temporal Ctx	10.3	Control 2	60.7
		Parietal Ctx
Control 2 Temporal Ctx	35.6	Control 3	26.4
		Parietal Ctx
Control 3 Temporal Ctx	37.4	Control (Path) 1	79.6
		Parietal Ctx
Control 4 Temporal Ctx	16.2	Control (Path) 2	45.7
		Parietal Ctx
Control (Path) 1	81.8	Control (Path) 3	9.2
Temporal Ctx		Parietal Ctx
Control (Path) 2	61.6	Control (Path) 4	83.5
Temporal Ctx		Parietal Ctx

[0938]

TABLE ACC
General_screening_panel_v1.4
	Rel. Exp.		Rel. Exp.
	(%) Ag4492,		(%) Ag4492,
	Run		Run
Tissue Name	222666072	Tissue Name	222666072
Adipose	5.8	Renal ca. TK-10	9.7
Melanoma*	4.0	Bladder	4.0
Hs688(A).T
Melanoma*	6.8	Gastric ca. (liver	8.1
Hs688(B).T		met.) NCI-N87
Melanoma* M14	15.9	Gastric ca.	0.1
		KATO III
Melanoma* LOXIMVI	14.0	Colon ca. SW-948	0.0
Melanoma*	0.0	Colon ca. SW480	0.2
SK-MEL-5
Squamous cell	0.3	Colon ca.*	1.6
cell carcinoma SCC-4		(SW480 met)
		SW620
Testis Pool	2.7	Colon ca. HT29	0.0
Prostate ca.*	0.0	Colon ca. HCT-116	0.0
(bone met) PC-3
Prostate Pool	12.9	Colon ca. CaCo-2	0.2
Placenta	1.2	Colon cancer tissue	2.6
Uterus Pool	3.3	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	36.1	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	12.3	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	9.4	Colon Pool	4.6
Ovarian ca. OVCAR-5	14.3	Small Intestine Pool	5.7
Ovarian ca. IGROV-1	8.2	Stomach Pool	3.5
Ovarian ca. OVCAR-8	4.1	Bone Marrow Pool	2.8
Ovary	8.2	Fetal Heart	15.2
Breast ca. MCF-7	0.0	Heart Pool	3.8
Breast ca.	6.4	Lymph Node Pool	4.0
MDA-MB-231
Breast ca. BT 549	41.5	Fetal Skeletal	6.7
		Muscle
Breast ca. T47D	18.9	Skeletal Muscle	2.2
		Pool
Breast ca. MDA-N	0.0	Spleen Pool	10.5
Breast Pool	4.5	Thymus Pool	3.3
Trachea	3.9	CNS cancer	4.4
		(glio/astro)
		U87-MG
Lung	3.5	CNS cancer	0.9
		(glio/astro)
		U-118-MG
Fetal Lung	67.4	CNS cancer	100.0
		(neuro;met)
		SK-N-AS
Lung ca. NCI-N417	3.8	CNS cancer	8.0
		(astro) SF-539
Lung ca. LX-1	0.0	CNS cancer	1.7
		(astro) SNB-75
Lung ca. NCI-H146	1.2	CNS cancer	7.6
		(glio) SNB-19
Lung ca. SHP-77	15.1	CNS cancer	0.0
		(glio) SF-295
Lung ca. A549	6.2	Brain (Amygdala)	2.8
		Pool
Lung ca. NCI-H526	0.1	Brain (cerebellum)	0.9
Lung ca. NCI-H23	2.8	Brain (fetal)	10.1
Lung ca. NCI-H460	0.4	Brain	3.3
		(Hippocampus) Pool
Lung ca. HOP-62	4.2	Cerebral Cortex	7.7
		Pool
Lung ca. NCI-H522	0.2	Brain (Substantia	4.9
		nigra ) Pool
Liver	0.7	Brain	6.3
		(Thalamus) Pool
Fetal Liver	10.1	Brain (whole)	3.9
Liver ca. HepG2	4.3	Spinal Cord Pool	1.5
Kidney Pool	6.3	Adrenal Gland	5.8
Fetal Kidney	35.8	Pituitary gland Pool	3.7
Renal ca. 786-0	15.4	Salivary Gland	2.4
Renal ca. A498	0.4	Thyroid (female)	4.8
Renal ca. ACHN	10.4	Pancreatic ca.	0.0
		CAPAN2
Renal ca. UO-31	0.1	Pancreas Pool	6.3

[0939]

TABLE ACD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4492,		Ag4492,
Tissue Name	Run 195481931	Tissue Name	Run 195481931
Secondary Th1 act	5.2	HUVEC IL-1beta	43.5
Secondary Th2 act	32.5	HUVEC IFN gamma	57.8
Secondary Tr1 act	18.4	HUVEC TNF alpha + IFN gamma	27.2
Secondary Th1 rest	0.3	HUVEC TNF alpha + IL4	24.8
Secondary Th2 rest	2.5	HUVEC IL-11	46.0
Secondary Tr1 rest	1.8	Lung Microvascular EC none	54.7
Primary Th1 act	2.6	Lung Microvascular EC TNFalpha +	18.4
		IL-1beta
Primary Th2 act	4.9	Microvascular Dermal EC none	15.5
Primary Tr1 act	6.2	Microsvasular Dermal EC	3.3
		TNFalpha + IL-1beta
Primary Th1 rest	0.1	Bronchial epithelium TNFalpha +	7.1
		IL1beta
Primary Th2 rest	0.1	Small airway epithelium none	11.8
Primary Tr1 rest	1.5	Small airway epithelium TNFalpha +	19.5
		IL-1beta
CD45RA CD4 lymphocyte act	2.7	Coronery artery SMC rest	100.0
CD45RO CD4 lymphocyte act	0.1	Coronery artery SMC TNFalpha +	94.0
		IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	11.7
Secondary CD8 lymphocyte rest	0.0	Astrocytes TNFalpha + IL-1beta	5.7
Secondary CD8 lymphocyte act	1.3	KU-812 (Basophil) rest	0.0
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	1.3	CCD1106 (Keratinocytes) none	0.3
CH11
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNFalpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	44.8
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	14.0
LAK cells IL-2 + IFN gamma	0.0	NCI-H292 IL-4	20.0
LAK cells IL-2 + IL-18	0.3	NCI-H292 IL-9	30.4
LAK cells PMA/ionomycin	0.0	NCI-H292 IL-13	29.7
NK Cells IL-2 rest	0.2	NCI-H292 IFN gamma	20.6
Two Way MLR 3 day	0.0	HPAEC none	19.9
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1 beta	78.5
Two Way MLR 7 day	0.0	Lung fibroblast none	45.4
PBMC rest	0.0	Lung fibroblast TNF alpha + IL-1	73.7
		beta
PBMC PWM	0.0	Lung fibroblast IL-4	39.5
PBMC PHA-L	0.0	Lung fibroblast IL-9	40.9
Ramos (B cell) none	0.0	Lung fibroblast IL-13	31.9
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	30.4
B lymphocytes PWM	0.2	Dermal fibroblast CCD1070 rest	10.2
B lymphocytes CD40L and IL-4	0.0	Dermal fibroblast CCD1070 TNF	7.8
		alpha
EOL-1 dbcAMP	13.7	Dermal fibroblast CCD1070 IL-1	10.9
		beta
EOL-1 dbcAMP	23.0	Dermal fibroblast IFN gamma	16.2
PMA/ionomycin
Dendritic cells none	0.0	Dermal fibroblast IL-4	34.2
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	30.1
Dendnitic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.0	Neutrophils rest	0.1
Monocytes LPS	0.0	Colon	6.7
Macrophages rest	0.0	Lung	74.7
Macrophages LPS	0.0	Thymus	11.6
HUVEC none	29.9	Kidney	34.4
HUVEC starved	61.1

[0940]

TABLE ACE
general oncology screening panel_v_2.4
	Rel. Exp.		Rel. Exp.
	(%) Ag4492,		(%) Ag4492,
	Run		Run
Tissue Name	268690026	Tissue Name	268690026
Colon cancer 1	4.2	Bladder NAT 2	0.7
Colon NAT 1	2.0	Bladder NAT 3	0.3
Colon cancer 2	4.2	Bladder NAT 4	4.8
Colon NAT 2	1.8	Prostate	68.8
		adenocarcinoma 1
Colon cancer 3	6.2	Prostate	8.7
		adenocarcinoma 2
Colon NAT 3	6.3	Prostate	11.6
		adenocarcinoma 3
Colon malignant	4.2	Prostate	5.3
cancer 4		adenocarcinoma 4
Colon NAT 4	1.4	Prostate NAT 5	5.4
Lung cancer 1	3.3	Prostate	5.3
		adenocarcinoma 6
Lung NAT 1	4.1	Prostate	9.4
		adenocarcinoma 7
Lung cancer 2	73.7	Prostate	3.3
		adenocarcinoma 8
Lung NAT 2	15.6	Prostate	34.4
		adenocarcinoma 9
Squamous cell	5.1	Prostate NAT 10	4.1
carcinoma 3
Lung NAT 3	1.5	Kidney cancer 1	27.5
Metastatic	21.5	Kidney NAT 1	10.9
melanoma 1
Melanoma 2	1.3	Kidney cancer 2	100.0
Melanoma 3	2.8	Kidney NAT 2	12.6
Metastatic	50.7	Kidney cancer 3	24.7
melanoma 4
Metastatic	77.9	Kidney NAT 3	4.6
melanoma 5
Bladder cancer 1	2.6	Kidney cancer 4	8.5
Bladder NAT 1	0.0	Kidney NAT 4	2.5
Bladder cancer 2	6.1

[0941] CNS_neurodegeneration_v1.0 Summary: Ag4492 This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. This gene appears to be slightly down-regulated in the temporal cortex of Alzheimer's disease patients. Therefore, up-regulation of this gene or its protein product, or treatment with specific agonists for this receptor may be of use in reversing the dementia, memory loss, and neuronal death associated with this disease.

[0942] General_screening_panel_v1.4 Summary: Ag4492 Highest expression of this gene is seen in a brain cancer cell line (CT=23.4). High levels of expression are also seen in cell lines derived from breast, ovarian, lung and renal cancers. Thus, expression of this gene could be used to differentiate these samples from other samples on this panel and as a marker of these cancers. Therapeutic modulation of the expression or function of this gene may be useful in the treatment of brain, breast, ovarian, lung and renal cancers.

[0943] In addition, this gene is expressed at much higher levels in fetal lung and liver tissue (CTs=24-25) when compared to expression in the adult counterpart (CTs=27-28). This expression is also indicative of a role for this protein in cellular growth and differentiation. Thus, expression of this gene may be used to differentiate between the fetal and adult source of these tissues.

[0944] Among tissues with metabolic function, this gene is expressed at high to moderate levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0945] This gene is also expressed at high to moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0946] Panel 4.1D Summary: Ag4492 This gene is most highly expressed in resting coronary artery smooth muscle cells (CT=27.8). Moderate levels of expression are also seen in endothelial cells and fibroblasts from lung and skin, including HPAEC, HUVEC and lung microvascular EC. Therefore, therapies designed with the protein encoded by this transcript could be important in regulating endothelium function including leukocyte extravasation, a major component of inflammation during asthma, IBD, and psoriasis.

[0947] general oncology screening panel_v—2.4 Summary: Ag4492 This gene is widely expressed in this panel, with highest expression in kidney cancer (CT=25.2). In addition, this gene is more highly expressed in lung cancer than in the corresponding normal adjacent tissue, with prominent expression also detected in prostate and melanoma cancers. Thus, expression of this gene could be used as a marker of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of lung cancer.

[0948] AD. CG119685-01: Ubiquitin C-terminal Hydrolase UCH37

[0949] Expression of gene CG119685-01 was assessed using the primer-probe set Ag4513, described in Table ADA. Results of the RTQ-PCR runs are shown in Table ADB.

TABLE ADA
Probe Name Ag4513
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gtctcagactcctgagctcaag-3′	22	791	274
Probe	TET-5′-tcgacctccaaagtggtacagtgaa-3′-TAMRA	26	826	275
Reverse	5′-cagacacaatggccattaaatt-3′	22	867	276

[0950]

TABLE ADB
General_screening_panel_v1.4
	Rel. Exp.		Rel. Exp.
	(%) Ag4513,		(%) Ag4513,
	Run		Run
Tissue Name	222711720	Tissue Name	222711720
Adipose	7.5	Renal ca. TK-10	35.4
Melanoma*	7.5	Bladder	17.8
Hs688(A).T
Melanoma*	10.2	Gastric ca. (liver	49.7
Hs688(B).T		met.) NCI-N87
Melanoma* M14	37.6	Gastric ca.	60.7
		KATO III
Melanoma* LOXIMVI	29.7	Colon ca. SW-948	20.7
Melanoma*	57.8	Colon ca. SW480	41.5
SK-MEL-5
Squamous cell	29.7	Colon ca.*	31.6
carcinoma SCC-4		(SW480 met)
		SW620
Testis Pool	6.2	Colon ca. HT29	18.9
Prostate ca.*	17.3	Colon ca. HCT-116	75.3
(bone met) PC-3
Prostate Pool	9.9	Colon ca. CaCo-2	13.0
Placenta	1.2	Colon cancer tissue	15.1
Uterus Pool	5.0	Colon ca. SW1116	4.8
Ovarian ca. OVCAR-3	38.4	Colon ca. Colo-205	4.8
Ovarian ca. SK-OV-3	42.3	Colon ca. SW-48	10.7
Ovarian ca. OVCAR-4	55.9	Colon Pool	10.9
Ovarian ca. OVCAR-5	14.0	Small Intestine Pool	9.6
Ovarian ca. IGROV-1	11.6	Stomach Pool	6.2
Ovarian ca. OVCAR-8	8.8	Bone Marrow Pool	4.9
Ovary	5.0	Fetal Heart	9.0
Breast ca. MCF-7	29.5	Heart Pool	6.9
Breast ca.	100.0	Lymph Node Pool	10.0
MDA-MB-231
Breast ca. BT 549	83.5	Fetal Skeletal	8.2
		Muscle
Breast ca. T47D	31.6	Skeletal Muscle	20.7
		Pool
Breast ca. MDA-N	14.3	Spleen Pool	8.4
Breast Pool	9.8	Thymus Pool	9.4
Trachea	7.4	CNS cancer	26.2
		(glio/astro)
		U87-MG
Lung	3.4	CNS cancer	38.4
		(glio/astro)
		U-118-MG
Fetal Lung	25.3	CNS cancer	73.7
		(neuro;met)
		SK-N-AS
Lung ca. NCI-N417	18.3	CNS cancer	22.1
		(astro) SF-539
Lung ca. LX-1	41.5	CNS cancer	35.4
		(astro) SNB-75
Lung ca. NCI-H146	4.6	CNS cancer	15.7
		(glio) SNB-19
Lung ca. SHP-77	17.0	CNS cancer	22.2
		(glio) SF-295
Lung ca. A549	16.4	Brain (Amygdala)	15.9
		Pool
Lung ca. NCI-H526	6.2	Brain (cerebellum)	10.4
Lung ca. NCI-H23	31.0	Brain (fetal)	8.6
Lung ca. NCI-H460	34.9	Brain	19.6
		(Hippocampus) Pool
Lung ca. HOP-62	4.3	Cerebral Cortex	23.8
		Pool
Lung ca. NCI-H522	25.9	Brain (Substantia	15.4
		nigra ) Pool
Liver	0.4	Brain	33.4
		(Thalamus) Pool
Fetal Liver	18.4	Brain (whole)	15.0
Liver ca. HepG2	6.2	Spinal Cord Pool	8.9
Kidney Pool	19.3	Adrenal Gland	4.9
Fetal Kidney	17.2	Pituitary gland Pool	4.5
Renal ca. 786-0	19.1	Salivary Gland	1.5
Renal ca. A498	11.2	Thyroid (female)	3.2
Renal ca. ACHN	2.1	Pancreatic ca.	32.3
		CAPAN2
Renal ca. UO-31	18.0	Pancreas Pool	15.0

[0951] General_screening_panel_v1.4 Summary: Ag4513 Highest expression of this gene is seen in a breast cancer cell line (CT=28.7). This gene is widely expressed in this panel, with prominent expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0952] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0953] This gene is also expressed at moderate to low levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0954] In addition, this gene is expressed at much higher levels in fetal liver tissue (CTs=31.2) when compared to expression in the adult counterpart (CTs=36.7). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.

[0955] AE. CG120443-01 and CG120443-02: Focal Adhesion Kinase 1

[0956] Expression of gene CG120443-01 and CG120443-02 was assessed using the primer-probe set Ag6092, described in Table AEA. Results of the RTQ-PCR runs are shown in Table AEB.

TABLE AEA
Probe Name Ag6092
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-attcgttatttgccaaaaggat-3′	22	424	277
Probe	TET-5′-ccagtttactgaagataagccaactttga-3′-TAMRA	29	453	278
Reverse	5′-taatcgctcttcacctgttgat-3′	22	491	279

[0957]

TABLE AEB
General_screening_panel_v1.5
	Rel. Exp.		Rel. Exp.
	(%) Ag6092,		(%) Ag6092,
	Run		Run
Tissue Name	248501664	Tissue Name	248501664
Adipose	8.6	Renal ca. TK-10	56.3
Melanoma*	15.2	Bladder	17.7
Hs688(A).T
Melanoma*	14.6	Gastric ca. (liver	91.4
Hs688(B).T		met.) NCI-N87
Melanoma* M14	21.8	Gastric ca.	47.3
		KATO III
Melanoma* LOXIMVI	36.1	Colon ca. SW-948	5.6
Melanoma*	51.8	Colon ca. SW480	23.3
SK-MEL-5
Squamous cell	26.6	Colon ca.*	18.6
cell carcinoma SCC-4		(SW480 met)
		SW620
Testis Pool	15.0	Colon ca. HT29	42.0
Prostate ca.*	77.9	Colon ca. HCT-116	46.7
(bone met) PC-3
Prostate Pool	14.4	Colon ca. CaCo-2	33.7
Placenta	8.0	Colon cancer tissue	18.0
Uterus Pool	9.5	Colon ca. SW1116	2.9
Ovarian ca. OVCAR-3	34.4	Colon ca. Colo-205	4.5
Ovarian ca. SK-OV-3	35.4	Colon ca. SW-48	8.7
Ovarian ca. OVCAR-4	27.7	Colon Pool	24.3
Ovarian ca. OVCAR-5	80.1	Small Intestine Pool	17.8
Ovarian ca. IGROV-1	22.7	Stomach Pool	11.7
Ovarian ca. OVCAR-8	19.2	Bone Marrow Pool	7.6
Ovary	16.7	Fetal Heart	14.8
Breast ca. MCF-7	18.6	Heart Pool	9.4
Breast ca.	53.2	Lymph Node Pool	16.3
MDA-MB-231
Breast ca. BT 549	84.1	Fetal Skeletal	8.3
		Muscle
Breast ca. T47D	13.2	Skeletal Muscle	11.0
		Pool
Breast ca. MDA-N	13.2	Spleen Pool	12.2
Breast Pool	25.5	Thymus Pool	11.6
Trachea	11.4	CNS cancer	17.7
		(glio/astro)
		U87-MG
Lung	3.8	CNS cancer	42.6
		(glio/astro)
		U-118-MG
Fetal Lung	45.1	CNS cancer	34.9
		(neuro;met)
		SK-N-AS
Lung ca. NCI-N417	2.5	CNS cancer	18.2
		(astro) SF-539
Lung ca. LX-1	18.8	CNS cancer	52.9
		(astro) SNB-75
Lung ca. NCI-H146	8.7	CNS cancer	23.8
		(glio) SNB-19
Lung ca. SHP-77	29.1	CNS cancer	45.4
		(glio) SF-295
Lung ca. A549	34.2	Brain (Amygdala)	24.0
		Pool
Lung ca. NCI-H526	12.2	Brain (cerebellum)	77.9
Lung ca. NCI-H23	100.0	Brain (fetal)	36.9
Lung ca. NCI-H460	14.9	Brain	18.7
		(Hippocampus) Pool
Lung ca. HOP-62	25.5	Cerebral Cortex	35.6
		Pool
Lung ca. NCI-H522	28.9	Brain (Substantia	25.2
		nigra ) Pool
Liver	1.5	Brain	36.1
		(Thalamus) Pool
Fetal Liver	11.0	Brain (whole)	36.3
Liver ca. HepG2	14.7	Spinal Cord Pool	19.5
Kidney Pool	31.4	Adrenal Gland	18.3
Fetal Kidney	22.2	Pituitary gland Pool	6.2
Renal ca. 786-0	37.1	Salivary Gland	9.3
Renal ca. A498	13.3	Thyroid (female)	17.1
Renal ca. ACHN	32.1	Pancreatic ca.	25.2
		CAPAN2
Renal ca. UO-31	44.4	Pancreas Pool	20.4

[0958] General_screening_panel_v1.5 Summary: Ag6092 Highest expression of this gene is seen in a lung cancer cell line (CT=23.6). This gene is widely expressed in this panel, with high levels of expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. In addition, this gene encodes a protein with homology to focal adhesion kinase (FAK). Activation of these kinases may be an early step in intracellular signal transduction triggered by interactions with extracellular matrix adhesive molecules. Thus, modulation of this gene product may be useful in the treatment of cancer.

[0959] Among tissues with metabolic function, this gene is expressed at high levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0960] This gene is also expressed at high levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0961] In addition, this gene is, expressed at much higher levels in fetal lung tissue (CTs=24.8) when compared to expression in the adult counterpart (CTs=28.3). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.

[0962] AF. CG120563-01 and CG120563-02: Mitochondrial Isoleucine TRNA Synthetase

[0963] Expression of gene CG120563-01 and CG120563-02 was assessed using the primer-probe set Ag4506, described in Table AFA. Results of the RTQ-PCR runs are shown in Tables AFB, AFC and AFD. Please note that CG120563-02 represents a full-length physical clone of the CG120563-01 gene, validating the prediction of the gene sequence.

TABLE AFA
Probe Name Ag4506
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gcatctgttgcttctactttgg-3′	22	1129	280
Probe	TET-5′-catttgagactatttcaacactttcaggtg-3′-TAMRA	30	1157	281
Reverse	5′-tgcaagtaccattttccaaatc-3′	22	1189	282

[0964]

TABLE AFB
CNS_neurodegeneration_v1.0
	Rel. Exp.		Rel. Exp.
	(%) Ag4506,		(%) Ag4506,
	Run		Run
Tissue Name	224704540	Tissue Name	224704540
AD 1 Hippo	18.2	Control (Path) 3	6.9
		Temporal Ctx
AD 2 Hippo	23.2	Control (Path) 4	25.2
		Temporal Ctx
AD 3 Hippo	5.9	AD 1 Occipital	15.3
		Ctx
AD 4 Hippo	8.3	AD 2 Occipital	0.0
		Ctx (Missing)
AD 5 hippo	75.8	AD 3 Occipital	6.9
		Ctx
AD 6 Hippo	67.8	AD 4 Occipital	19.9
		Ctx
Control 2 Hippo	28.3	AD 5 Occipital	43.2
		Ctx
Control 4 Hippo	13.5	AD 6 Occipital	17.8
		Ctx
Control (Path) 3 Hippo	11.0	Control 1	6.1
		Occipital Ctx
AD 1 Temporal Ctx	17.2	Control 2	59.5
		Occipital Ctx
AD 2 Temporal Ctx	27.5	Control 3	13.9
		Occipital Ctx
AD 3 Temporal Ctx	6.7	Control 4	6.0
		Occipital Ctx
AD 4 Temporal Ctx	16.6	Control (Path) 1	77.4
		Occipital Ctx
AD 5 Inf Temporal Ctx	100.0	Control (Path) 2	12.1
		Occipital Ctx
AD 5 Sup Temporal Ctx	61.1	Control (Path) 3	5.5
		Occipital Ctx
AD 6 Inf Temporal Ctx	51.1	Control (Path) 4	15.5
		Occipital Ctx
AD 6 Sup Temporal Ctx	56.3	Control 1	8.2
		Parietal Ctx
Control 1 Temporal Ctx	8.1	Control 2	45.4
		Parietal Ctx
Control 2 Temporal Ctx	44.1	Control 3	19.9
		Parietal Ctx
Control 3 Temporal Ctx	17.9	Control (Path) 1	70.2
		Parietal Ctx
Control 3 Temporal Ctx	10.9	Control (Path) 2	17.7
		Parietal Ctx
Control (Path) 1	48.3	Control (Path) 3	8.4
Temporal Ctx		Parietal Ctx
Control (Path) 2	33.2	Control (Path) 4	36.9
Temporal Ctx		Parietal Ctx

[0965]

TABLE AFC
General_screening_panel_v1.4
	Rel. Exp.		Rel. Exp.
	(%) Ag4506,		(%) Ag4506,
	Run		Run
Tissue Name	222695222	Tissue Name	222695222
Adipose	8.0	Renal ca. TK-10	53.2
Melanoma*	22.1	Bladder	16.4
Hs688(A).T
Melanoma*	23.0	Gastric ca. (liver	39.5
Hs688(B).T		met.) NCI-N87
Melanoma* M14	45.4	Gastric ca.	74.7
		KATO III
Melanoma* LOXIMVI	36.9	Colon ca. SW-948	16.0
Melanoma*	86.5	Colon ca. SW480	66.0
SK-MEL-5
Squamous cell	23.7	Colon ca.*	44.1
carcinoma SCC-4		(SW480 met)
		SW620
Testis Pool	7.0	Colon ca. HT29	24.3
Prostate ca.*	100.0	Colon ca. HCT-116	86.5
(bone met) PC-3
Prostate Pool	4.6	Colon ca. CaCo-2	54.3
Placenta	5.6	Colon cancer tissue	18.9
Uterus Pool	2.4	Colon ca. SW1116	10.7
Ovarian ca. OVCAR-3	41.8	Colon ca. Colo-205	23.0
Ovarian ca. SK-OV-3	61.1	Colon ca. SW-48	12.8
Ovarian ca. OVCAR-4	11.7	Colon Pool	10.3
Ovarian ca. OVCAR-5	39.5	Small Intestine Pool	6.7
Ovarian ca. IGROV-1	24.5	Stomach Pool	5.7
Ovarian ca. OVCAR-8	14.6	Bone Marrow Pool	2.9
Ovary	7.9	Fetal Heart	9.9
Breast ca. MCF-7	47.3	Heart Pool	5.0
Breast ca.	69.7	Lymph Node Pool	8.2
MDA-MB-231
Breast ca. BT 549	40.6	Fetal Skeletal	4.3
		Muscle
Breast ca. T47D	94.6	Skeletal Muscle	9.7
		Pool
Breast ca. MDA-N	27.0	Spleen Pool	4.4
Breast Pool	9.0	Thymus Pool	7.1
Trachea	7.6	CNS cancer	40.1
		(glio/astro)
		U87-MG
Lung	0.8	CNS cancer	41.5
		(glio/astro)
		U-118-MG
Fetal Lung	10.2	CNS cancer	54.0
		(neuro;met)
		SK-N-AS
Lung ca. NCI-N417	7.9	CNS cancer	14.3
		(astro) SF-539
Lung ca. LX-1	42.9	CNS cancer	48.3
		(astro) SNB-75
Lung ca. NCI-H146	10.7	CNS cancer	26.4
		(glio) SNB-19
Lung ca. SHP-77	51.4	CNS cancer	44.4
		(glio) SF-295
Lung ca. A549	57.0	Brain (Amygdala)	6.8
		Pool
Lung ca. NCI-H526	2.8	Brain (cerebellum)	3.8
Lung ca. NCI-H23	56.6	Brain (fetal)	11.2
Lung ca. NCI-H460	47.6	Brain	8.0
		(Hippocampus) Pool
Lung ca. HOP-62	24.5	Cerebral Cortex	7.0
		Pool
Lung ca. NCI-H522	56.3	Brain (Substantia	6.8
		nigra ) Pool
Liver	2.0	Brain	11.7
		(Thalamus) Pool
Fetal Liver	11.5	Brain (whole)	6.5
Liver ca. HepG2	27.2	Spinal Cord Pool	5.9
Kidney Pool	16.4	Adrenal Gland	15.1
Fetal Kidney	10.1	Pituitary gland Pool	2.0
Renal ca. 786-0	38.2	Salivary Gland	4.5
Renal ca. A498	21.5	Thyroid (female)	4.5
Renal ca. ACHN	32.8	Pancreatic ca.	47.6
		CAPAN2
Renal ca. UO-31	22.5	Pancreas Pool	10.7

[0966]

TABLE AFD
Panel 4.1D
	Rel. Exp.		Rel. Exp.
	(%) Ag4506,		(%) Ag4506,
	Run		Run
Tissue Name	197487869	Tissue Name	197487869
Secondary Th1 act	69.7	HUVEC IL-1beta	46.7
Secondary Th2 act	75.3	HUVEC IFN gamma	38.4
Secondary T41 act	54.3	HUVEC TNF alpha +	31.2
		IFN gamma
Secondary Th1 rest	10.8	HUVEC TNF alpha +	40.6
		IL4
Secondary Th2 rest	29.5	HUVEC IL-11	21.9
Secondary Tr1 rest	14.8	Lung Microvascular	71.7
		EC none
Primary Th1 act	39.5	Lung Microvascular	50.7
		EC TNFalpha +
		IL-1beta
Primary Th2 act	61.6	Microvascular Dermal	47.0
		EC none
Primary Tr1 act	41.5	Microsvasular Dermal	38.2
		EC TNFalpha +
		IL-1beta
Primary Th1 rest	17.7	Bronchial epithelium	43.8
		TNFalpha + IL1beta
Primary Th2 rest	12.6	Small airway	28.5
		epithelium none
Primary Tr1 rest	34.6	Small airway	57.4
		epithelium
		TNFalpha + IL-1beta
CD45RA CD4	61.1	Coronery artery SMC	40.6
lymphocyte act		rest
CD45RO CD4	70.2	Coronery artery SMC	38.4
lymphocyte act		TNFalpha + IL-1beta
CD8 lymphocyte act	57.4	Astrocytes rest	17.1
Secondary CD8	60.3	Astrocytes	21.2
lymphocyte rest		TNFalpha + IL-1beta
Secondary CD8	29.9	KU-812 (Basophil)	51.8
lymphocyte act		rest
CD4 lymphocyte	12.5	KU-812 (Basophil)	62.9
none		PMA/ionomycin
2ry Th1/Th2/	26.4	CCD1106	60.3
Tr1_anti-CD95		(Keratinocytes) none
CH11
LAK cells rest	36.9	CCD1106	32.1
		(Keratinocytes)
		TNFalpha + IL-1beta
LAK cells IL-2	33.4	Liver cirrhosis	7.9
LAK cells IL-2 +	24.5	NCI-H292 none	58.2
IL-12
LAK cells IL-2 +	19.6	NCI-H292 IL-4	80.7
IFN gamma
LAK cells IL-2 +	30.4	NCI-H292 IL-9	100.0
IL-18
LAK cells PMA/	14.7	NCI-H292 IL-13	99.3
ionomycin
NK Cells IL-2 rest	44.1	NCI-H292 IFN gamma	73.2
Two Way MLR 3	25.5	HPAEC none	23.7
day
Two Way MLR 5	33.9	HPAEC TNF alpha +	44.1
day		IL-1 beta
Two Way MLR 7	21.9	Lung fibroblast none	27.2
day
PBMC rest	10.2	Lung fibroblast TNF	29.9
		alpha + IL-1 beta
PBMC PWM	46.7	Lung fibroblast IL-4	43.8
PBMC PHA-L	54.3	Lung fibroblast IL-9	43.8
Ramos (B Cell)	60.7	Lung fibroblast IL-13	40.3
none
Ramos (B cell)	73.2	Lung fibroblast IFN	47.6
ionomycin		gamma
B lymphocytes	42.3	Dermal fibroblast	54.3
PWM		CCD1070 rest
B lymphocytes	35.4	Dermal fibroblast	80.7
CD40L and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	44.1	Dermal fibroblast	38.2
		CCD1070 IL-1 beta
EOL-1 dbcAMP	19.5	Dermal fibroblast IFN	33.7
PMA/ionomycin		gamma
Dendritic cells none	43.2	Dermal fibroblast IL-4	73.2
Dendritic cells LPA	31.6	Dermal Fibroblasts	33.7
		rest
Dendritic cells anti-	55.1	Neutrophils TNFa +	0.2
CD40		LPA
Monocytes rest	21.3	Neutrophils rest	3.0
Monocytes LPS	14.3	Colon	10.8
Macrophages rest	47.6	Lung	13.7
Macrophages LPS	17.2	Thymus	10.7
HUVEC none	28.5	Kidney	36.9
HUVEC starved	48.0

[0967] CNS_neurodegeneration_v1.0 Summary: Ag4506 This expression profile confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.

[0968] General_screening_panel_v1.4 Summary: Ag4506 Highest expression of this gene is seen in a prostate cancer cell line (CT=25). This gene is widely expressed in this panel, with high levels of expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0969] Among tissues with metabolic function, this gene is expressed at moderate levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0970] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0971] In addition, this gene is expressed at much higher levels in fetal lung tissue (CT=28.3) when compared to expression in the adult counterpart (CT=31.9). Thus, expression of this gene may be used to differentiate between the fetal and adult source of these tissue

[0972] Panel 4.1D Summary: Ag4506 Highest expression of this gene is seen in a IL-9 treated NCI-H292 cells (CT=28). This gene is also expressed at moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0973] AG. CG122872-01: Vacuolar ATP Synthase 16 KDA Proteolipid Subunit

[0974] Expression of gene CG122872-01 was assessed using the primer-probe set Ag4543, described in Table AGA. Results of the RTQ-PCR runs are shown in Tables AGB, AGC and AGD.

TABLE AGA
Probe Name Ag4543
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggctttgccatagacatcttg-3′	21	318	283
Probe	TET-5′-cagcagccccgactattcatggg-3′-TAMRA	23	366	284
Reverse	5′-ggaagatgaggatcaggatcat-3′	22	390	285

[0975]

TABLE AGB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4543, Run		Ag4546, Run
Tissue Name	224721286	Tissue Name	224721286
AD 1 Hippo	8.9	Control (Path) 3 Temporal Ctx	12.2
AD 2 Hippo	66.9	Control (Path) 4 Temporal Ctx	7.0
AD 3 Hippo	21.8	AD 1 Occipital Ctx	42.0
AD 4 Hippo	0.0	AD 2 Occipital Ctx (Missing)	0.0
AD 5 hippo	33.2	AD 3 Occipital Ctx	9.0
AD 6 Hippo	75.8	AD 4 Occipital Ctx	55.5
Control 2 Hippo	76.3	AD 5 Occipital Ctx	26.2
Control 4 Hippo	0.0	AD 6 Occipital Ctx	15.2
Control (Path) 3 Hippo	0.0	Control 1 Occipital Ctx	0.0
AD 1 Temporal Ctx	3.3	Control 2 Occipital Ctx	53.2
AD 2 Temporal Ctx	14.2	Control 3 Occipital Ctx	11.7
AD 3 Temporal Ctx	0.0	Control 4 Occipital Ctx	21.3
AD 4 Temporal Ctx	9.3	Control (Path) 1 Occipital Ctx	66.0
AD 5 Inf Temporal Ctx	34.9	Control (Path) 2 Occipital Ctx	16.6
AD 5 SupTemporal Ctx	0.0	Control (Path) 3 Occipital Ctx	11.5
AD 6 Inf Temporal Ctx	21.9	Control (Path) 4 Occipital Ctx	19.9
AD 6 Sup Temporal Ctx	100.0	Control 1 Parietal Ctx	15.7
Control 1 Temporal Ctx	0.0	Control 2 Parietal Ctx	22.1
Control 2 Temporal Ctx	24.7	Control 3 Parietal Ctx	5.0
Control 3 Temporal Ctx	23.3	Control (Path) 1 Parietal Ctx	76.3
Control 4 Temporal Ctx	4.4	Control (Path) 2 Parietal Ctx	12.2
Control (Path) 1 Temporal Ctx	74.2	Control (Path) 3 Parietal Ctx	0.0
Control (Path) 2 Temporal Ctx	44.1	Control (Path) 4 Parietal Ctx	13.3

[0976]

TABLE AGC
General_screening_panel_v1.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4543,		Ag4543,
	Run		Run
Tissue Name	222809444	Tissue Name	222809444
Adipose	0.0	Renal ca. TK-10	0.0
Melanoma* Hs688(A).T	5.4	Bladder	2.9
Melanoma* Hs688(B).T	5.7	Gastric ca. (liver met.) NCI-N87	0.0
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	0.0
Squamous cell carcinoma SCC-	0.0	Colon ca.* (SW480 met) SW620	0.0
4
Testis Pool	4.3	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.0	Colon ca. HCT-116	0.0
Prostate Pool	1.2	Colon ca. CaCo-2	0.9
Placenta	0.6	Colon cancer tissue	0.7
Uterus Pool	12.6	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.0	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.9	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	1.2	Colon Pool	6.3
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	18.0
Ovarian ca. IGROV-1	0.0	Stomach Pool	7.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	1.0
Ovary	7.2	Fetal Heart	6.0
Breast ca. MCF-7	0.5	Heart Pool	0.1
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	9.6
Breast ca. BT 549	0.5	Fetal Skeletal Muscle	4.3
Breast ca. T47D	0.1	Skeletal Muscle Pool	0.9
Breast ca. MDA-N	0.0	Spleen Pool	2.0
Breast Pool	3.3	Thymus Pool	3.2
Trachea	2.9	CNS cancer (glio/astro) U87-MG	0.8
Lung	2.6	CNS cancer (glio/astro) U-118-MG	1.9
Fetal Lung	8.5	CNS cancer (neuro;met) SK-N-AS	0.6
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-75	0.6
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	100.0	CNS cancer (glio) SF-295	0.0
Lung ca. A549	0.3	Brain (Amygdala) Pool	2.1
Lung ca. NCI-H526	0.0	Brain (cerebellum)	13.6
Lung ca. NCI-H23	0.9	Brain (fetal)	6.6
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	3.3
Lung ca. HOP-62	0.1	Cerebral Cortex Pool	3.3
Lung ca. NCI-H522	0.0	Brain (Substantia nigra) Pool	2.6
Liver	0.8	Brain (Thalamus) Pool	6.8
Fetal Liver	0.0	Brain (whole)	3.8
Liver ca. HepG2	0.0	Spinal Cord Pool	1.5
Kidney Pool	14.8	Adrenal Gland	5.0
Fetal Kidney	2.4	Pituitary gland Pool	2.0
Renal ca. 786-0	0.0	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	6.2

[0977]

TABLE AGD
Panel 4.1D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4543,		Ag4543,
	Run		Run
Tissue Name	198395822	Tissue Name	198395822
Secondary Th1 act	6.9	HUVEC IL-1beta	0.0
Secondary Th2 act	13.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	13.2	HUVEC TNF alpha + IFN gamma	0.0
Secondary Th1 rest	6.9	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	2.8
Secondary Tr1 rest	0.0	Lung Microvascular EC none	2.2
Primary Th1 act	10.7	Lung Microvascular EC TNFalpha +	0.0
		IL-1beta
Primary Th2 act	2.0	Microvascular Dermal EC none	5.9
Primary Tr1 act	4.2	Microvascular Dermal EC TNFalpha +	7.6
		IL-1beta
Primary Th1 rest	3.4	Bronchial epithelium TNFalpha +	0.0
		IL1beta
Primary Th2 rest	6.7	Small airway epithelium none	0.0
Primary Tr1 rest	2.6	Small airway epithelium TNFalpha +	0.0
		IL-1beta
CD45RA CD4 lymphocyte act	9.2	Coronery artery SMC rest	0.0
CD45RO CD4 lymphocyte act	5.2	Coronery artery SMC TNFalpha + IL-	0.0
		1beta
CD8 lymphocyte act	7.4	Astrocytes rest	0.0
Secondary CD8 lymphocyte rest	1.8	Astrocytes TNFalpha + IL-1beta	3.6
Secondary CD8 lymphocyte act	0.0	KU-812 (Basophil) rest	0.0
CD4 lymphocyte none	14.8	KU-812 (Basophil) PMA/ionomycin	0.0
2ry Th1/Th2/Tr1_anti-CD95 CH11	13.9	CCD1106 (Keratinocytes) none	0.0
LAK cells rest	0.0	CCD1106 (Keratinocytes) TNFalpha +	0.0
		IL-1beta
LAK cells IL-2	2.9	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	3.4	NCI-H292 none	0.0
LAK cells IL-2 + IFN gamma	0.0	NCI-H292 IL-4	0.0
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells PMA/ionomycin	3.7	NCI-H292 IL-13	0.0
NK Cells IL-2 rest	2.3	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	13.7	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1 beta	10.0
Two Way MLR 7 day	1.7	Lung fibroblast none	38.2
PBMC rest	2.2	Lung fibroblast TNF alpha + IL-1 beta	6.5
PBMC PWM	6.0	Lung fibroblast IL-4	9.3
PBMC PHA-L	0.0	Lung fibroblast IL-9	23.2
Ramos (B cell) none	0.0	Lung fibroblast IL-13	11.1
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	11.2
B lymphocytes PWM	0.0	Dermal fibroblast CCD1070 rest	13.4
B lymphocytes CD40L and IL-4	0.0	Dermal fibroblast CCD1070 TNF alpha	15.4
EOL-1 dbcAMP	3.3	Dermal fibroblast CCD1070 IL-1 beta	7.8
EOL-1 dbcAMP PMA/ionomycin	0.0	Dermal fibroblast IFN gamma	4.5
Dendritic cells none	0.0	Dermal fibroblast IL-4	26.2
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	14.1
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.5	Neutrophils rest	0.9
Monocytes LPS	0.0	Colon	5.9
Macrophages rest	0.0	Lung	6.7
Macrophages LPS	0.0	Thymus	3.3
HUVEC none	6.6	Kidney	100.0
HUVEC starved	0.0

[0978] CNS_neurodegeneration_v1.0 Summary: Ag4543 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. See Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.

[0979] General_screening_panel_v1.4 Summary: Ag4543 Expression of the CG122872-01 gene is highest in a lung cancer cell line (CT=29.7). In addition, this gene is expressed at low but significant levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Furthermore, expression of this gene is primarily associated with normal tissues rather than cancer cell lines, suggesting that expression of this gene may be downregulated in tumors.

[0980] Among tissues with metabolic or endocrine function, this gene is expressed at low levels in pancreas, adipose, adrenal gland, fetal skeletal muscle, fetal heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0981] Panel 4.1D Summary: Ag4543 Expression of the CG122872-01 gene is highest in kidney (CT=32.3). Therefore, therapeutic targeting of the expression or function of this gene may modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis. In addition, low but significant expression of this gene is seen in lung and dermal fibroblasts, suggesting that this gene may be involved in normal conditions as well as pathological and inflammatory lung and skin disorders such as chronic obstructive pulmonary disease, asthma, allergy, emphysema and psoriasis.

[0982] AH. CG123772-01: Novel Transporter Like Protein

[0983] Expression of gene CG123772-01 was assessed using the primer-probe set Ag4557, described in Table AHA. Results of the RTQ-PCR runs are shown in Tables AHB, AHC and AHD.

TABLE AHA
Probe Name Ag4557
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cctctccggtttaaagcactt-3′	21	962	286
Probe	TET-5′-accctctctgtggtgtttggaaccat-3′-TAMRA	26	983	287
Reverse	5′-gtctccacgttggggataag-3′	20	1022	288

[0984]

TABLE AHB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%) Ag4557,		Rel. Exp. (%) Ag4557,
Tissue Name	Run 224723437	Tissue Name	Run 224723437
AD 1 Hippo 1	27.9	Control (Path) 3	13.5
		Temporal Ctx
AD 2 Hippo	53.6	Control (Path) 4	33.7
		Temporal Ctx
AD 3 Hippo	20.7	AD 1 Occipital Ctx	28.5
AD 4 Hippo	18.9	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	100.0	AD 3 Occipital Ctx	18.9
AD 6 Hippo	69.3	AD 4 Occipital Ctx	30.1
Control 2 Hippo	36.9	AD 5 Occipital Ctx	0.0
Control 4 Hippo	45.7	AD 6 Occipital Ctx	43.8
Control (Path) 3	4.3	Control 1 Occipital	14.9
Hippo		Ctx
AD 1 Temporal Ctx	31.6	Control 2 Occipital	75.3
		Ctx
AD 2 Temporal Ctx	39.8	Control 3 Occipital	23.3
		Ctx
AD 3 Temporal Ctx	22.8	Control 3 Occipital	23.3
		Ctx
AD 4 Temporal Ctx	18.4	Control (Path) 1	81.2
		Occipital Ctx
AD 5 Inf Temporal	76.8	Control (Path) 2	18.3
Ctx		Occipital Ctx
AD 5 SupTemporal	99.3	Control (Path) 3	5.4
Ctx		Occipital Ctx
AD 6 Inf Temporal	56.3	Control (Path) 4	24.0
Ctx		Occipital Ctx
AD 6 Sup Temporal	65.5	Control 1 Parietal	21.2
Ctx		Ctx
Control 1 Temporal	14.7	Control 2 Parietal	80.7
Ctx		Ctx
Control 2 Temporal	59.9	Control 3 Parietal	20.9
Ctx		Ctx
Control 3 Temporal	20.3	Control (Path) 1	63.7
Ctx		Parietal Ctx
Control 4 Temporal	16.0	Control (Path) 2	39.2
Ctx		Parietal Ctx
Control (Path) 1	64.2	Control (Path) 3	13.6
Temporal Ctx		Parietal Ctx
Control (Path) 2	42.0	Control (Path) 4	47.0
Temporal Ctx		Parietal Ctx

[0985]

TABLE AHC
General_screening_panel_v1.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4557,		Ag4557,
	Run		Run
Tissue Name	222810056	Tissue Name	222810056
Adipose	5.4	Renal ca. TK-10	33.4
Melanoma* Hs688(A).T	29.9	Bladder	21.3
Melanoma* Hs688(B).T	40.6	Gastric ca. (liver met.) NCI-N87	38.2
Melanoma* M14	27.9	Gastric ca. KATO III	63.3
Melanoma* LOXIMVI	24.5	Colon ca. SW-948	11.3
Melanoma* SK-MEL-5	74.2	Colon ca. SW480	26.8
Squamous cell carcinoma SCC-	11.0	Colon ca.* (SW480 met) SW620	24.3
4
Testis Pool	9.7	Colon ca. HT29	17.8
Prostate ca.* (bone met) PC-3	18.4	Colon ca. HCT-116	38.4
Prostate Pool	6.2	Colon ca. CaCo-2	26.6
Placenta	24.3	Colon cancer tissue	16.3
Uterus Pool	2.5	Colon ca. SW1116	7.1
Ovarian ca. OVCAR-3	23.0	Colon ca. Colo-205	9.0
Ovarian ca. SK-OV-3	28.5	Colon ca. SW-48	13.1
Ovarian ca. OVCAR-4	17.3	Colon Pool	9.8
Ovarian ca. OVCAR-5	60.7	Small Intestine Pool	5.8
Ovarian ca. IGROV-1	15.8	Stomach Pool	7.0
Ovarian ca. OVCAR-8	13.3	Bone Marrow Pool	4.8
Ovary	16.2	Fetal Heart	3.3
Breast ca. MCF-7	31.9	Heart Pool	4.5
Breast ca. MDA-MB-231	26.1	Lymph Node Pool	12.4
Breast ca. BT 549	44.1	Fetal Skeletal Muscle	2.8
Breast ca. T47D	100.0	Skeletal Muscle Pool	5.0
Breast ca. MDA-N	22.5	Spleen Pool	10.7
Breast Pool	10.2	Thymus Pool	9.1
Trachea	13.4	CNS cancer (glio/astro) U87-MG	21.3
Lung	1.4	CNS cancer (glio/astro) U-118-	24.1
		MG
Fetal Lung	10.1	CNS cancer (neuro;met) SK-N-AS	20.7
Lung ca. NCI-N417	2.9	CNS cancer (astro) SF-539	41.8
Lung ca. LX-1	21.0	CNS cancer (astro) SNB-75	42.3
Lung ca. NCI-H146	5.4	CNS cancer (glio) SNB-19	19.3
Lung ca. SHP-77	45.7	CNS cancer (glio) SF-295	70.7
Lung ca. A549	47.0	Brain (Amygdala) Pool	4.8
Lung ca. NCI-H526	4.3	Brain (cerebellum)	8.1
Lung ca. NCI-H23	18.9	Brain (fetal)	4.5
Lung ca. NCI-H460	15.6	Brain (Hippocampus) Pool	5.5
Lung ca. HOP-62	36.1	Cerebral Cortex Pool	4.3
Lung ca. NCI-H522	20.4	Brain (Substantia nigra) Pool	4.9
Liver	9.2	Brain (Thalamus) Pool	5.6
Fetal Liver	10.8	Brain (whole)	3.4
Liver ca. HepG2	13.3	Spinal Cord Pool	7.7
Kidney Pool	17.1	Adrenal Gland	14.3
Fetal Kidney	5.5	Pituitary gland Pool	10.9
Renal ca. 786-0	24.5	Salivary Gland	15.0
Renal ca. A498	12.0	Thyroid (female)	12.9
Renal ca. ACHN	11.0	Pancreatic ca. CAPAN2	35.1
Renal ca. UO-31	21.8	Pancreas Pool	20.4

[0986]

TABLE AHD
Panel 4.1D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4557,		Ag4557,
	Run		Run
Tissue Name	199319741	Tissue Name	199319741
Secondary Th1 act	54.7	HUVEC IL-1beta	58.2
Secondary Th2 act	94.6	HUVEC IFN gamma	52.9
Secondary Tr1 act	71.7	HUVEC TNF alpha + IFN gamma	51.4
Secondary Th1 rest	27.7	HUVEC TNF alpha + IL4	67.8
Secondary Th2 rest	77.4	HUVEC IL-11	34.2
Secondary Tr1 rest	34.9	Lung Microvascular EC none	100.0
Primary Th1 act	30.1	Lung Microvascular EC	68.3
		TNFalpha + IL-1beta
Primary Th2 act	54.0	Microvascular Dermal EC none	33.4
Primary Tr1 act	37.1	Microsvasular Dermal EC	31.9
		TNFalpha + IL-1beta
Primary Th1 rest	13.8	Bronchial epithelium TNFalpha +	17.0
		IL1beta
Primary Th2 rest	11.5	Small airway epithelium none	9.2
Primary Tr1 rest	42.9	Small airway epithelium	17.6
		TNFalpha + IL-1beta
CD45RA CD4 lymphocyte act	52.1	Coronery artery SMC rest	33.4
CD45RO CD4 lymphocyte act	43.8	Coronery artery SMC TNFalpha +	45.1
		IL-1beta
CD8 lymphocyte act	33.7	Astrocytes rest	16.5
Secondary CD8 lymphocyte	39.0	Astrocytes TNFalpha + IL-1beta	24.8
rest
Secondary CD8 lymphocyte act	23.2	KU-812 (Basophil) rest	49.7
CD4 lymphocyte none	10.9	KU-812 (Basophil)	48.6
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	36.9	CCD1106 (Keratinocytes) none	30.4
CH11
LAK cells rest	42.6	CCD1106 (Keratinocytes)	22.5
		TNFalpha + IL-1beta
LAK cells IL-2	39.8	Liver cirrhosis	12.5
LAK cells IL-2 + IL-12	23.7	NCI-H292 none	39.5
LAK cells IL-2 + IFN gamma	18.4	NCI-H292 IL-4	53.2
LAK cells IL-2 + IL-18	24.7	NCI-H292 IL-9	62.9
LAK cells PMA/ionomycin	25.3	NCI-H292 IL-13	64.2
NK Cells IL-2 rest	82.4	NCI-H292 IFN gamma	43.2
Two Way MLR 3 day	38.4	HPAEC none	39.2
Two Way MLR 5 day	24.7	HPAEC TNF alpha + IL-1 beta	76.8
Two Way MLR 7 day	25.5	Lung fibroblast none	43.5
PBMC rest	29.5	Lung fibroblast TNF alpha + IL-1	44.4
		beta
PBMC PWM	35.4	Lung fibroblast IL-4	26.2
PBMC PHA-L	35.6	Lung fibroblast IL-9	33.4
Ramos (B cell) none	32.3	Lung fibroblast IL-13	22.8
Ramos (B cell) ionomycin	45.7	Lung fibroblast IFN gamma	39.5
B lymphocytes PWM	20.0	Dermal fibroblast CCD1070 rest	73.2
B lymphocytes CD40L and IL-	49.3	Dermal fibroblast CCD1070 TNF	94.0
4		alpha
EOL-1 dbcAMP	69.3	Dermal fibroblast CCD1070 IL-1	54.0
		beta
EOL-1 dbcAMP	39.8	Dermal fibroblast IFN gamma	33.0
PMA/ionomycin
Dendritic cells none	45.1	Dermal fibroblast IL-4	39.5
Dendritic cells LPS	28.9	Dermal Fibroblasts rest	28.7
Dendritic cells anti-CD40	64.6	Neutrophils TNFa + LPS	3.3
Monocytes rest	73.7	Neutrophils rest	25.7
Monocytes LPS	82.4	Colon	19.3
Macrophages rest	51.4	Lung	24.8
Macrophages LPS	27.7	Thymus	13.7
HUVEC none	40.9	Kidney	49.0
HUVEC starved	71.7

[0987] CNS_neurodegeneration_v1.0 Summary: Ag4557 This panel confirms the expression of this gene at moderate to low levels in the brains of an independent group of individuals. See Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.

[0988] General_screening_panel_v1.4 Summary: Ag4557 Expression of the CG123772-01 gene is highest in a breast cancer cell line (CT=25). This gene is expressed at moderate to high levels across the majority of samples on this panel. Expression of this gene appears to be upregulated in lung, CNS, and breast cancer cell lines when compared to the corresponding normal tissues. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of lung, CNS and breast cancer.

[0989] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0990] In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0991] Panel 4.1D Summary: Ag4557 The CG123772-01 gene is expressed at moderate to low levels in a wide range of cell types of significance in the immune response in health and disease. These cells include T-cells, B-cells, endothelial cells, macrophages, monocytes, eosinophils, basophils, neutrophils, peripheral blood mononuclear cells, lung and skin epithelial cells, lung and skin fibroblast cells, as well as normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0992] AI. CG124021-01: Ketohexokinase Like

[0993] Expression of gene CG124021-01 was assessed using the primer-probe set Ag5927, described in Table AIA. Results of the RTQ-PCR runs are shown in Tables AIB, AIC and AID.

TABLE AIA
Probe Name Ag5927
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cagatcaaccttctcaaagtctgtag-3′	26	609	289
Probe	TET-5′-acatctggcaggctctcagcaacat-3′-TAMRA	25	640	290
Reverse	5′-ccttcatgggctcaatgg-3′	18	674	291

[0994]

TABLE AIB
AI_comprehensive panel_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag5928, Run		Ag5928, Run
Tissue Name	256424088	Tissue Name	256424088
110967 COPD-F	0.0	112427 Match Control Psoriasis-F	2.9
110980 COPD-F	9.3	112418 Psoriasis-M	0.0
110968 COPD-M	0.0	112723 Match Control Psoriasis-M	0.0
110977 COPD M	13.4	112419 Psoriasis-M	3.3
110989 Emphysema-F	0.0	112424 Match Control Psoriasis-M	0.0
110992 Emphysema-F	0.0	112420 Psoriasis-M	16.3
110993 Emphysema-F	0.0	112425 Match Control Psoriasis-M	4.2
110994 Emphysema-F	0.0	104689 (MF) OA Bone-Backus	0.0
110995 Emphysema-F	0.0	104690 (MF) Adj “Normal” Bone	6.4
		Backus
110996 Emphysema-F	0.0	104691 (MF) OA Synovium-	4.7
		Backus
110997 Asthma-M	0.0	104692 (BA) OA Cartilage-Backus	0.0
111001 Asthma-F	3.6	104694 (BA) OA Bone-Backus	14.2
111002 Asthma-F	7.7	104695 (BA) Adj “Normal” Bone-	5.1
		Backus
111003 Asthma-F	0.0	104696 (BA) OA Synovium-	0.0
		Backus
111004 Atopic Asthma-F	0.0	104700 (SS) OA Bone-Backus	10.0
111005 Atopic Asthma-F	0.0	104701 (SS) Adj “Normal” Bone-
		Backus
111006 Atopic Asthma-F	0.0	104702 (SS) OA Synovium-Backus	4.8
111417 Allergy-M	0.0	117093 OA Cartilage Rep7	0.0
112347 Allergy-M	0.0	112672 OA Bone5	0.0
112349 Normal Lung-F	2.1	112673 OA Synovium5	3.9
112357 Normal Lung-F	0.0	112674 OA Synovial Fluid cells5	0.0
112354 Normal Lung-M	4.4	117100 OA Cartilage Rep14	0.0
112374 Crohns-F	0.0	112756 OA Bone9	100.0
112389 Match Control Crohns-F	8.1	112757 OA Synovium9	0.0
112375 Crohns-F	0.0	112758 OA Synovial Fluid Cells9	0.0
112732 Match Control Crohns-F	0.0	117125 RA Cartilage Rep2	4.0
112725 Crohns-M	0.0	113492 Bone2 RA	2.5
112387 Match Control Crohns-	4.2	113493 Synovium2 RA	0.0
M
112378 Crohns-M	0.0	113494 Syn Fluid Cells RA	3.9
112390 Match Control Crohns-	3.2	113499 Cartilage4 RA	0.0
M
112726 Crohns-M	0.0	113500 Bone4 RA	13.3
112731 Match Control Crohns-	0.0	113501 Synovium4 RA	0.0
M
112380 Ulcer Col-F	6.3	113502 Syn Fluid Cells4 RA	0.0
112734 Match Control Ulcer	5.4	113495 Cartilage3 RA	0.0
Col-F
112384 Ulcer Col-F	5.5	113496 Bone3 RA	4.1
112737 Match Control Ulcer	0.0	113497 Synovium3 RA	0.0
Col-F
112386 Ulcer Col-F	0.0	113498 Syn Fluid Cells3 RA	0.0
112738 Match Control Ulcer	16.7	117106 Normal Cartilage Rep20	1.2
Col-F
112381 Ulcer Col-M	0.0	113663 Bone3 Normal	4.1
112735 Match Control Ulcer	3.3	113664 Synovium3 Normal	0.0
Col-M
112382 Ulcer Col-M	4.3	113665 Syn Fluid Cells3 Normal	0.0
112394 Match Control Ulcer	0.0	117107 Normal Cartilage Rep22	0.0
Col-M
112383 Ulcer Col-M	0.0	113667 Bone4 Normal	0.0
112736 Match Control Ulcer	0.0	113668 Synovium4 Normal	0.0
Col-M
112423 Psoriasis-F	0.0	113669 Syn Fluid Cells4 Normal	0.0

[0995]

TABLE AIC
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5927,		Ag5927,
	Run		Run
Tissue Name	249286665	Tissue Name	249286665
AD 1 Hippo	7.9	Control (Path) 3 Temporal Ctx	0.0
AD 2 Hippo	40.6	Control (Path) 4 Temporal Ctx	29.3
AD 3 Hippo	0.0	AD 1 Occipital Ctx	14.9
AD 4 Hippo	7.4	AD 2 Occipital Ctx (Missing)	0.0
AD 5 hippo	98.6	AD 3 Occipital Ctx	7.2
AD 6 Hippo	21.6	AD 4 Occipital Ctx	12.5
Control 2 Hippo	31.2	AD 5 Occipital Ctx	7.2
Control 4 Hippo	1.7	AD 6 Occipital Ctx	47.6
Control (Path) 3 Hippo	6.6	Control 1 Occipital Ctx	1.6
AD 1 Temporal Ctx	3.6	Control 2 Occipital Ctx	100.0
AD 2 Temporal Ctx	22.1	Control 3 Occipital Ctx	23.8
AD 3 Temporal Ctx	4.8	Control 4 Occipital Ctx	3.3
AD 4 Temporal Ctx	14.6	Control (Path) 1 Occipital Ctx	43.8
AD 5 Inf Temporal Ctx	92.0	Control (Path) 2 Occipital Ctx	6.1
AD 5 SupTemporal Ctx	28.9	Control (Path) 3 Occipital Ctx	1.9
AD 6 Inf Temporal Ctx	27.2	Control (Path) 4 Occipital Ctx	7.6
AD 6 Sup Temporal Ctx	12.8	Control 1 Parietal Ctx	3.1
Control 1 Temporal Ctx	12.9	Control 2 Parietal Ctx	29.7
Control 2 Temporal Ctx	52.5	Control 3 Parietal Ctx	7.9
Control 3 Temporal Ctx	13.1	Control (Path) 1 Parietal Ctx	63.7
Control 4 Temporal Ctx	8.0	Control (Path) 2 Parietal Ctx	10.6
Control (Path) 1 Temporal Ctx	44.4	Control (Path) 3 Parietal Ctx	1.7
Control (Path) 2 Temporal Ctx	31.0	Control (Path) 4 Parietal Ctx	28.1

[0996]

TABLE AID
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5927,		Ag5927,
	Run		Run
Tissue Name	247609170	Tissue Name	247609170
Adipose	0.0	Renal ca. TK-10	11.8
Melanoma* Hs688(A).T	0.0	Bladder	1.7
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.) NCI-N87	0.0
Melanoma* M14	2.5	Gastric ca. KATO III	24.5
Melanoma* LOXIMVI	0.8	Colon ca. SW-948	23.3
Melanoma* SK-MEL-5	12.7	Colon ca. SW480	46.7
Squamous cell carcinoma SCC-	0.6	Colon ca.* (SW480 met) SW620	50.3
4
Testis Pool	10.2	Colon ca. HT29	2.9
Prostate ca.* (bone met) PC-3	9.0	Colon ca. HCT-116	13.0
Prostate Pool	0.0	Colon ca. CaCo-2	13.9
Placenta	0.0	Colon cancer tissue	26.1
Uterus Pool	2.0	Colon ca. SW1116	9.1
Ovarian ca. OVCAR-3	2.6	Colon ca. Colo-205	3.7
Ovarian ca. SK-OV-3	2.3	Colon ca. SW-48	16.7
Ovarian ca. OVCAR-4	3.1	Colon Pool	0.8
Ovarian ca. OVCAR-5	6.6	Small Intestine Pool	1.9
Ovarian ca. IGROV-1	10.1	Stomach Pool	0.6
Ovarian ca. OVCAR-8	2.5	Bone Marrow Pool	0.0
Ovary	0.5	Fetal Heart	0.0
Breast ca. MCF-7	11.1	Heart Pool	0.0
Breast ca. MDA-MB-231	19.6	Lymph Node Pool	0.0
Breast ca. BT 549	0.7	Fetal Skeletal Muscle	0.6
Breast ca. T47D	1.2	Skeletal Muscle Pool	2.2
Breast ca. MDA-N	8.3	Spleen Pool	0.5
Breast Pool	0.0	Thymus Pool	1.8
Trachea	0.5	CNS cancer (glio/astro) U87-MG	6.1
Lung	0.6	CNS cancer (glio/astro) U-118-	12.8
		MG
Fetal Lung	1.8	CNS cancer (neuro;met) SK-N-AS	9.0
Lung ca. NCI-N417	7.7	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	5.0	CNS cancer (astro) SNB-75	2.0
Lung ca. NCI-H146	21.2	CNS cancer (glio) SNB-19	9.9
Lung ca. SHP-77	19.1	CNS cancer (glio) SF-295	3.5
Lung ca. A549	21.3	Brain (Amygdala) Pool	18.4
Lung ca. NCI-H526	13.1	Brain (cerebellum)	100.0
Lung ca. NCI-H23	33.9	Brain (fetal)	21.6
Lung ca. NCI-H460	0.6	Brain (Hippocampus) Pool	10.5
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	21.8
Lung ca. NCI-H522	8.9	Brain (Substantia nigra) Pool	18.6
Liver	0.0	Brain (Thalamus) Pool	17.6
Fetal Liver	2.2	Brian (whole)	23.2
Liver ca. HepG2	16.5	Spinal Cord Pool	6.3
Kidney Pool	0.7	Adrenal Gland	1.1
Fetal Kidney	0.6	Pituitary gland Pool	0.5
Renal ca. 786-0	0.0	Salivary Gland	0.7
Renal ca. A498	0.6	Thyroid (female)	1.1
Renal ca. ACHN	6.1	Pancreatic ca. CAPAN2	4.3
Renal ca. UO-31	0.0	Pancreas Pool	3.6

[0997] AI_comprehensive panel_v1.0 Summary: Ag5927 Expression of this gene is limited to a single sample of osteoarthritic bone (CT=33.4). Therefore, expression of this gene could be used to distinguish this sample from the other samples on this panel.

[0998] CNS_neurodegeneration_v1.0 Summary: Ag5927 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. See Panel 1.5 for a discussion of this gene in treatment of central nervous system disorders.

[0999] General_screening_panel_v1.5 Summary: Ag5927 Expression of the CG124021-01 gene is highest in cerebellum (CT=32.1). In addition, this gene is expressed at low levels in all other regions of the central nervous system examined, including amygdala, substantia nigra, thalamus, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[1000] In addition, this gene is expressed at low levels in lung and colon cancer cell lines. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of lung cancer or colon cancer.

[1001] Panel 5 Islet Summary: Ag5927 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[1002] AJ. CG124021-02: Ketohexokinase

[1003] Expression of gene CG124021-02 was assessed using the primer-probe set Ag5914, described in Table AJA. Results of the RTQ-PCR runs are shown in Tables AJB, AJC and AJD.

TABLE AJA
Probe Name Ag5914
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-caactcctgcaccgttctc-3′	19	140	292
Probe	TET-5′-cttcatgggctcaatggctcctg-3′-TAMRA	23	182	293
Reverse	5′-caccaggaagtcagcaacat-3′	20	208	294

[1004]

TABLE AJB
General_screening_panel_v1.5
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag5914, Run		Ag5914, Run
Tissue Name	247608926	Tissue Name	247608926
Adipose	0.0	Renal ca. TK-10	2.6
Melanoma* Hs688(A).T	0.0	Bladder	0.1
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.) NCI-N87	0.0
Melanoma* M14	0.0	Gastric ca. KATO III	0.5
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.5
Melanoma* SK-MEL-5	0.1	Colon ca. SW480	0.3
Squamous cell carcinoma SCC-	0.0	Colon ca.* (SW480 met) SW620	0.3
4
Testis Pool	0.1	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.1	Colon ca. HCT-116	0.1
Prostate Pool	0.0	Colon ca. CaCo-2	0.3
Placenta	0.0	Colon cancer tissue	0.4
Uterus Pool	0.0	Colon ca. SW1116	0.1
Ovarian ca. OVCAR-3	0.0	Colon ca. Colo-205	0.1
Ovarian ca. SK-OV-3	0.0	Colon ca. SW-48	0.4
Ovarian ca. OVCAR-4	0.0	Colon Pool	0.0
Ovarian ca. OVCAR-5	0.1	Small Intestine Pool	0.0
Ovarian ca. IGROV-1	0.2	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.1	Heart Pool	0.0
Breast ca. MDA-MB-231	0.1	Lymph Node Pool	0.0
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.1	Spleen Pool	0.1
Breast Pool	0.0	Thymus Pool	0.0
Trachea	0.0	CNS cancer (glio/astro) U87-MG	0.1
Lung	0.0	CNS cancer (glio/astro) U-118-	0.1
		MG
Fetal Lung	0.0	CNS cancer (neuro;met) SK-N-AS	0.1
Lung ca. NCI-N417	0.1	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.1	CNS cancer (astro) SNB-75	0.0
Lung ca. NCI-H146	0.1	CNS cancer (glio) SNB-19	0.1
Lung ca. SHP-77	0.1	CNS cancer (glio) SF-295	0.0
Lung ca. A549	0.1	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	0.1	Brain (cerebellum)	0.2
Lung ca. NCI-H23	0.1	Brain (fetal)	0.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.1	Brain (Substantia nigra) Pool	0.0
Liver	33.0	Brain (Thalamus) Pool	0.0
Fetal Liver	10.2	Brain (whole)	0.1
Liver ca. HepG2	6.9	Spinal Cord Pool	0.0
Kidney Pool	0.1	Adrenal Gland	0.0
Fetal Kidney	1.1	Pituitary gland Pool	0.0
Renal ca. 786-0	0.0	Salivary Gland	0.1
Renal ca. A498	100.0	Thyroid (female)	0.0
Renal ca. ACHN	0.1	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	0.1

[1005]

TABLE AJC
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag5914, Run		Ag5914, Run
Tissue Name	247579025	Tissue Name	247579025
Secondary Th1 act	0.0	HUVEC IL-1 beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN gamma	0.0
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC none	0.1
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNFalpha + IL-1beta
Primary Th2 act	0.1	Microvascular Dermal EC none	0.0
Primary Tr1 act	0.1	Microsvasular Dermal EC	0.0
		TNFalpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium TNFalpha +	0.0
		IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	0.0
Primary Tr1 rest	0.0	Small airway epithelium	0.0
		TNFalpha + IL-1beta
CD45RA CD4 lymphocyte act	0.0	Coronery artery SMC rest	0.0
CD45RO CD4 lymphocyte act	0.0	Coronery artery SMC TNFalpha +	0.0
		IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8 lymphocyte rest	0.0	Astrocytes TNFalpha + IL-1beta	0.0
Secondary CD8 lymphocyte act	0.0	KU-812 (Basophil) rest	0.0
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95 CH11	0.0	CCD1106 (Keratinocytes) none	0.0
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNFalpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	6.2
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IFN gamma	0.0	NCI-H292 IL-4	0.0
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells PMA/ionomycin	0.0	NCI-H292 IL-13	0.3
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.0	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1 beta	0.0
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	0.0	Lung fibroblast TNF alpha + IL-1	0.0
		beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.0
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	0.0
B lymphocytes PWM	0.1	Thermal fibroblast CCD1070 rest	0.0
B lymphocytes CD40L and IL-4	0.0	Dermal fibroblast CCD1070 TNF	0.0
		alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070 IL-1	0.0
		beta
EOL-1 dbcAMP PMA/ionomycin	0.0	Dermal fibroblast IFN gamma	0.0
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.0
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	10.2
Macrophages rest	0.0	Lung	0.0
Macrophages LPS	0.0	Thymus	0.0
HUVEC none	0.0	Kidney	100.0
HUVEC starved	0.0

[1006]

TABLE AJD
Panel 5 Islet
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag5914, Run		Ag5914, Run
Tissue Name	247609818	Tissue Name	247609818
97457_Patient-02go_adipose	0.4	94709_Donor 2 AM - A_adipose	0.0
97476_Patient-07sk_skeletal	0.0	94710_Donor 2 AM - B_adipose	0.0
muscle
97477_Patient-07ut_uterus	0.0	94711_Donor 2 AM - C_adipose	0.0
97478_Patient-07pl_placenta	0.0	94712_Donor 2 AD - A_adipose	0.0
99167_Bayer Patient 1	11.7	94713_Donor 2 AD - B_adipose	0.7
97482_Patient-08ut_uterus	0.0	94714_Donor 2 AD - C_adipose	0.0
97483_Patient-08pl_placenta	0.0	94742_Donor 3 U - A_Mesenchymal	0.0
		Stem Cells
97486_Patient-09sk_skeletal	0.0	94743_Donor 3 U - B_Mesenchymal	0.0
muscle		Stem Cells
97487_Patient-09ut_uterus	0.0	94730_Donor 3 AM - A_adipose	0.0
97488_Patient-09pl_placenta	0.0	94731_Donor 3 AM - B_adipose	0.0
97492_Patient-10ut_uterus	0.0	94732_Donor 3 AM - C_adipose	0.0
97493_Patient-10pl_placenta	0.0	94733_Donor 3 AD - A_adipose	0.0
97495_Patient-11go_adipose	0.6	94734_Donor 3 AD - B_adipose	0.0
97496_Patient-11sk_skeletal	0.0	94735_Donor 3 AD - C_adipose	0.0
muscle
97497_Patient-11ut_uterus	0.0	77138_Liver_HepG2untreated	48.6
97498_Patient-11pl_placenta	0.0	73556_Heart_Cardiac stromal cells	0.0
		(primary)
97500_Patient-12go_adipose	0.0	81735_Small Intestine	100.0
97501_Patient-12sk_sketal	0.0	72409_Kidney_Proximal Convoluted	0.0
muscle		Tubule
97502_Patient-12ut_uterus	0.0	82685_Small intestine_Duodenum	86.5
97503_Patient-12pl_placenta	0.0	90650_Adrenal_Adrenocortical adenoma	0.0
94721_Donor 2 U -	0.0	72410_Kidney_HRCE	0.4
A_Mesenchymal Stem Cells
94722_Donor 2 U -	0.0	72411_Kidney_HRE	0.0
B_Mesenchymal Stem Cells
94723_Donor 2 U -	0.0	73139_Uterus_Uterine smooth muscle	0.0
C_Mesenchymal Stem Cells		cells

[1007] General_screening_panel_v1.5 Summary: Ag5914 Expression of the CG124021-02 gene is highest in a renal cancer cell line (CT=26.6). With this exception, moderate expression of this gene is restricted to adult and fetal liver as well as a liver cancer cell line. Therefore, expression of this gene may be used to distinguish liver from the other samples on this panel.

[1008] The CG124021-02 gene encodes a splice variant of ketohexokinase (KHK), also known as hepatic fructokinase. This enzyme catalyzes the first step of metabolism of dietary fructose, conversion of fructose to fructose-1-phosphate. Mutations in the ketohexokinase gene have been shown to be the cause of essential fructosuria, a benign, asymptomatic defect of intermediary metabolism [Bonthron et al., Hum. Molec. Genet. 3: 1627-1631, 1994, PubMed ID: 7833921]. Ketohexokinase, or fructokinase, like glucokinase (GCK) and glucokinase regulator (GCKR), is present in both liver and pancreatic islets. KHK is the first enzyme with a specialized pathway that catabolizes dietary fructose. The inhibition of GCK by GCKR is relieved by the binding of fructose-1-phosphate to GCKR. The role of glucokinase (GCK) as pancreatic beta cell glucose sensor and the finding of GCK mutations in maturity onset diabetes of the young (MODY) suggest GCKR as a further candidate gene for type 2 diabetes [Hayward et al., Mammalian Genome 7: 454-458, 1996, PubMed ID: 8662230]. In addition, KHK activity may affect the activity of GCK through the production of fructose-1-phosphate. Therefore, the CG124021-02 splice variant may play a role in the development of metabolic diseases, including fructosuria, obesity and type 2 diabetes.

[1009] Panel 4.1D Summary: Ag5914 Significant expression of the CG124021-02 gene is restricted to kidney (CT=29.3) and colon (CT=32.6). Thus, expression of this gene may be used to distinguish these samples from the other samples on this panel. Furthermore, therapeutic modulation of the activity of this gene or its protein product may be of benefit in the treatment of inflammatory or autoimmune diseases that affect the kidney and colon, including lupus, glomerulonephritis and inflammatory bowel disease.

[1010] Panel 5 Islet Summary: Ag5914 The CG124021-02 gene is expressed at low levels in small intestine and liver and is at the lower level of detection in pancreatic islet cells (CT=35.1). See Panel 1.5 for a description of the potential function of this gene in metabolic disorders.

[1011] AK. CG124021-04: Ketohexokinase

[1012] Expression of gene CG124021-04 was assessed using the primer-probe set Ag6258, described in Table AKA. Results of the RTQ-PCR runs are shown in Tables AKB and AKC.

TABLE AKA
Probe Name Ag6258
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggtagccgcaccatcctata-3′	20	376	295
Probe	TET-5′-ctatgacagcttcctggtggccgact-3′-TAMRA	26	396	296
Reverse	5′-ccaggccacctgagaca-3′	17	443	297

[1013]

TABLE AKB
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp.(%)
	Ag6258,		Ag6258,
	Run		Run
Tissue Name	258350023	Tissue Name	258359023
Adipose	0.0	Renal Ca. TK-10	7.3
Melanoma*	0.0	Bladder	0.5
Hs688(A).T
Melanoma*	0.0	Gastric Ca.	0.0
Hs688(B).T		(liver met.)
		NCI-N87
Melanoma* M14	0.0	Gastric Ca.	0.8
		KATO III
Melanoma*	0.0	Colon ca. SW-948	0.4
LOXIMVI
Melanoma*	0.0	Colon Ca. SW480	0.1
SK-MEL-5
Squamous cell	0.0	Colon ca.*	0.1
carcinoma SCC-4		(SW480 met)
		SW620
Testis Pool	0.0	Colon ca. HT29	0.0
Prostate ca.*	0.0	Colon ca. HCT-116	0.0
(bone met) PC-3
Prostate Pool	0.0	Colon ca. CaCo-2	0.6
Placenta	0.0	Colon cancer tissue	0.7
Uterus Pool	0.1	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.0	Colon ca. Colo-205	0.3
Ovarian ca. SK-OV-3	0.0	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	0.0
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	0.0
Ovarian ca. IGROV-1	0.0	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca.	0.0	Lymph Node Pool	0.0
MDA-MB-231
Breast ca. BT 549	0.0	Fetal Skeletal	0.0
		Muscle
Breast ca. T47D	0.0	Skeletal Muscle	0.0
		Pool
Breast ca. MDA-N	0.0	Spleen Pool	0.2
Breast Pool	0.0	Thymus Pool	0.0
Trachea	0.0	CNS cancer	0.0
		(glio/astro) U87-MG
Lung	0.0	CNS cancer	0.0
		(gilo/astro)
		U-118-MG
Fetal Lung	0.6	CNS cancer	0.0
		(neuro;met)
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer	0.0
		(astro) SF-539
Lung ca. LX-1	0.0	CNS cancer	0.0
		(astro) SNB-75
Lung Ca. NCI-H146	0.0	CNS cancer	0.0
		(glio) SNB-19
Lung Ca. SHP-77	0.0	CNS cancer	0.3
		(glio) SF-295
Lung Ca. A549	0.4	Brain (Amygdala)	0.0
		Pool
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.2
Lung ca. NCI-H23	0.1	Brain (fetal)	0.1
Lung ca. NCI-H460	0.0	Brain	0.0
		(Hippocampus) Pool
Lung ca. HOP-62	0.0	Cerebral Cortex	0.0
		Pool
Lung ca. NCI-H522	0.0	Brain	0.0
		(Substantia nigra)
		Pool
Liver	100.0	Brain (Thalamus)	0.0
		Pool
Fetal Liver	24.1	Brain (whole)	0.7
Liver ca. HepG2	16.7	Spinal Cord Pool	0.0
Kidney Pool	0.0	Adrenal Gland	0.2
Fetal Kidney	2.3	Pituitary gland Pool	0.0
Renal ca. 786-0	0.0	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca.	0.0
		CAPAN2
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[1014]

TABLE AKC
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag6258, Run		Ag6258, Run
Tissue Name	258416263	Tissue Name	258416263
Secondary Th1 act	0.0	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN gamma	0.0
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC none	0.0
Primary Th1 act	0.0	Lung Microvascular EC TNFalpha +	0.0
		IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC none	0.0
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNFalpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium TNFalpha +	0.0
		IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	0.0
Primary Tr1 rest	0.0	Small airway epithelium TNFalpha +	0.0
		IL-1beta
CD45RA CD4 lymphocyte act	0.0	Coronery artery SMC rest	0.0
CD45RO CD4 lymphocyte act	0.0	Coronery artery SMC TNFalpha +	0.0
		IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8 lymphocyte	0.0	Astrocytes TNFalpha + IL-1beta	0.0
rest
Secondary CD8 lymphocyte	0.0	KU-812 (Basophil) rest	10.0
act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	0.0	CCD1106 (Keratinocytes) none	0.0
CH11
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNFalpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	4.8
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IFN gamma	0.0	NCI-H292 IL-4	0.0
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells PMA/ionomycin	0.0	NCI-H292 IL-13	0.0
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.0	HPAEC none	0.0
Two Way MLR 5 day	0.0	HLPAEC TNF alpha + IL-1 beta	0.0
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	0.0	Lung fibroblast TNF alpha + IL-I	0.0
		beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.0
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	0.0
B lymphocytes PWM	0.0	Dermal fibroblast CCD1070 rest	0.0
B lymphocytes CD40L and	0.2	Dermal fibroblast CCD1070 TNF	0.0
IL-4		alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070 IL-1	0.0
		beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN gamma	0.0
PMA/ionomycin
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.0
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	3.5
Macrophages rest	0.0	Lung	0.0
Macrophages LPS	0.0	Thymus	0.0
HUVEC none	0.0	Kidney	100.0
HUVEC starved	0.0

[1015] General_screening_panel_v1.5 Summary: Ag6258 Expression of the CG124021-04 gene is restricted to adult (CT=30.3) and fetal liver (CT=32.4) as well as a liver cancer cell line (CT=32.9). Therefore, expression of this gene may be used to distinguish liver from the other samples on this panel. These results are in agreement with what was observed for splice variant CG124021-02; See Panel 1.5 description for CG124021-02 for a discussion of this gene in metabolic disease.

[1016] Panel 4.1D Summary: Ag5914 Significant expression of the CG124021-04 gene is restricted to kidney (CT=30.2). Thus, expression of this gene may be used to distinguish this sample from the other samples on this panel. Furthermore, therapeutic modulation of the activity of this gene or its protein product may be of benefit in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.

[1017] AL. CG150245-01 and CG150245-02: Aromatic-L-Amino-Acid Decarboxylase

[1018] Expression of gene CG150245-01 and CG150245-02 was assessed using the primer-probe set Ag6783, described in Table ALA. Results of the RTQ-PCR runs are shown in Tables ALB and ALC. Please note that CG150245-02 represents a full-length physical clone of the CG150245-01 gene, validating the prediction of the gene sequence.

TABLE ALA
Probe Name Ag6783
Primers	Sequences	Length	Start Position	SEQ ID No
Forward	5′-atcatcaacgacgttgagaagat-3′	23	216	298
Probe	TET-5′-cttgccgccccaggcatg-3′-TAMRA	18	242	299
Reverse	5′-cagtctccagctctgtgcat-3′	20	266	300

[1019]

TABLE ALB
General_screening_panel_v1.6
	Rel.		Rel.
	Exp. (%)		Exp.(%)
	Ag6783,		Ag6783,
	Run		Run
Tissue Name	278017430	Tissue Name	278017430
Adipose	0.0	Renal Ca. TK-10	0.8
Melanoma*	0.0	Bladder	0.4
Hs688(A).T
Melanoma*	0.0	Gastric Ca.	0.1
Hs688(B).T		(liver met.)
		NCI-N87
Melanoma* M14	0.0	Gastric Ca.	3.1
		KATO III
Melanoma*	0.0	Colon ca. SW-948	3.2
LOXIMVI
Melanoma*	0.0	Colon Ca. SW480	0.0
SK-MEL-5
Squamous cell	0.0	Colon ca.*	0.0
carcinoma		(SW480 met)
SCC-4		SW620
Testis Pool	0.0	Colon ca. HT29	4.0
Prostate ca.*	0.0	Colon ca. HCT-116	0.0
(bone met) PC-3
Prostate Pool	0.0	Colon ca. CaCo-2	15.4
Placenta	0.0	Colon cancer tissue	5.4
Uterus Pool	0.0	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.2	Colon ca. Colo-205	3.7
Ovarian ca. SK-OV-3	0.0	Colon ca. SW-48	9.2
Ovarian ca. OVCAR-4	0.0	Colon Pool	0.0
Ovarian ca. OVCAR-5	0.1	Small Intestine Pool	0.1
Ovarian ca. IGROV-1	0.0	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	0.1	Fetal Heart	0.0
Breast ca. MCF-7	0.1	Heart Pool	0.0
Breast ca.	0.0	Lymph Node Pool	0.0
MDA-MB-231
Breast ca. BT 549	0.0	Fetal Skeletal	0.0
		Muscle
Breast ca. T47D	0.0	Skeletal Muscle	0.0
		Pool
Breast ca. MDA-N	0.0	Spleen Pool	0.1
Breast Pool	0.0	Thymus Pool	0.0
Trachea	0.0	CNS cancer	0.0
		(glio/astro) U87-MG
Lung	0.0	CNS cancer	0.0
		(gilo/astro)
		U-118-MG
Fetal Lung	0.1	CNS cancer	17.4
		(neuro;met)
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer	0.0
		(astro) SF-539
Lung ca. LX-1	0.0	CNS cancer	0.0
		(astro) SNB-75
Lung Ca. NCI-H146	24.8	CNS cancer	0.0
		(glio) SNB-19
Lung Ca. SHP-77	100.0	CNS cancer	0.0
		(glio) SF-295
Lung Ca. A549	1.1	Brain (Amygdala)	0.0
		Pool
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.0
Lung ca. NCI-H23	0.0	Brain (fetal)	0.0
Lung ca. NCI-H460	0.0	Brain	0.0
		(Hippocampus) Pool
Lung ca. HOP-62	0.0	Cerebral Cortex	0.0
		Pool
Lung ca. NCI-H522	0.0	Brain	0.1
		(Substantia nigra)
		Pool
Liver	0.8	Brain (Thalamus)	0.0
		Pool
Fetal Liver	1.6	Brain (whole)	0.0
Liver ca. HepG2	0.9	Spinal Cord Pool	0.0
Kidney Pool	0.0	Adrenal Gland	0.7
Fetal Kidney	0.4	Pituitary gland Pool	0.0
Renal ca. 786-0	0.1	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca.	0.0
		CAPAN2
Renal ca. UO-31	0.0	Pancreas Pool	1.7

[1020]

TABLE ALC
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag6783, Run		Ag6783, Run
Tissue Name	278020631	Tissue Name	278020631
Secondary Th1 act	0.0	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN gamma	0.0
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC none	0.0
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNFalpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC none	0.0
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNFalpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium TNFalpha +	0.0
		IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	0.0
Primary Tr1 rest	0.0	Small airway epithelium	0.0
		TNFalpha + IL-1beta
CD45RA CD4 lymphocyte act	0.0	Coronery artery SMC rest	0.0
CD45RO CD4 lymphocyte act	0.0	Coronery artery SMC TNFalpha +	0.0
		IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8 lymphocyte rest	0.0	Astrocytes TNFalpha + IL-1beta	0.0
Secondary CD8 lymphocyte act	0.0	KU-812 (Basophil) rest	0.0
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95 CH11	0.0	CCD1106 (Keratinocytes) none	0.0
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNFalpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.6
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IFN gamma	0.0	NCI-H292 IL-4	0.0
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells PMA/ionomycin	0.0	NCI-H292 IL-13	0.0
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.0	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1 beta	0.0
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	0.0	Lung fibroblast TNF alpha + IL-1	0.0
		beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.0
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	0.0
B lymphocytes PWM	0.0	Thermal fibroblast CCD1070 rest	0.0
B lymphocytes CD40L and IL-4	0.0	Dermal fibroblast CCD1070 TNF	0.0
		alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070 IL-1	0.0
		beta
EOL-1 dbcAMP PMA/ionomycin	0.0	Dermal fibroblast IFN gamma	0.0
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.0
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	5.5
Macrophages rest	0.0	Lung	0.0
Macrophages LPS	0.0	Thymus	0.0
HUVEC none	0.0	Kidney	100.0
HUVEC starved	0.0

[1021] CNS_neurodegeneration_v1.0 Summary: Ag6783 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[1022] General_screening_panel_v1.6 Summary: Ag6783 Highest expression of this gene, which encodes a putative DOPA decarboxylase, is seen in a lung cancer cell line (CT=26.3). In addition, moderate levels of expression are seen in a cluster of cell lines derived from lung cancer, brain cancer, colon cancer, and gastric cancer.

[1023] Lung tumor cells and cell lines have been characterized by the expression of neuroendocrine (NE) features including DOPA decarboxylase, (Vos M D, J Cell Biochem Suppl 1996;24:257-68). In addition, small-cell carcinoma of the lung (SCCL) has been shown to undergo a process of dedifferentiation to a drug-resistant form and is associated with the concurrent loss of marker enzymes such dopa decarboxylase (DDC). (North W G, Peptides 1998;19(10):1743-7). Therefore, expression of this gene could be used to differentiate between the lung cancer cell lines and other samples on this panel and as a marker of the presence and/or progress of lung cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be of use in the treatment of lung cancer.

[1024] Low but significant levels of expression are seen in some metabolic tissues, including pancreas, adrenal and fetal and adult liver. A non-specific enzyme of aromatic L-amine acid decarboxylase (AAAD) that converts dihydroxyphenylalanine (DOPA) to dopamine is widely distributed in the peripheral tissue, e.g. the sympatho-adrenomedullary system, the small intestine, the lung, the liver, the kidney, etc. Since dopamine is one of the important endogenous hypotensive and natriuretic substances, it is speculated that impaired dopamine generation and/or the disturbance of the effects of dopamine could cause hypertension with suppression of plasma renin activity and/or salt-sensitivity. (Sigetomi S, Nippon Naibunpi Gakkai Zasshi Oct. 20, 1993;69(9):953-62)

[1025] Panel 4.1D Summary: Ag6783 This gene is only expressed at detectable levels in the kidney (CT=32). Thus, expression of this gene could be used to differentiate the kidney derived sample from other samples on this panel and as a marker of kidney tissue. In addition, therapeutic targeting of the expression or function of this gene may modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.

[1026] AM. CG55814-02: Glyceraldehyde-3-Phosphate Dehydrogenase

[1027] Expression of gene CG55814-02 was assessed using the primer-probe sets GAPDH(HUMAN), GAPDH FAM and Ag4439, described in Tables AMA, AMB and AMC. Results of the RTQ-PCR runs are shown in Tables AME, AME, AMF, AMG, AMH and AMI.

TABLE AMA
Probe Name GAPDH (HUMAN)
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-caacggatttggtcgtattg-3′	20	1096	366
Probe	TET-5′-tcaccagggctgcttttaactctggt-3′-TAMRA	26	1061	367
Reverse	5′-gaggtcaatgaaggggtcat-3′	20	1019	368

[1028]

TABLE AMB
Probe Name GAPDH FAM
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-aaagtggatattgttgccatca-3′	22	1039	301
Probe	TET-5′-ccccttcattgacctcaactacatgg-3′-TAMRA	26	1009	302
Reverse	5′-ggtggaatcatattggaacatg-3′	22	983	303

[1029]

TABLE AMC
Probe Name Ag4439
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cagagatgatgacccttttgg-3′-	21	772	304
Probe	TET-5′-aaatgagccccagccttctccatg-3′-TAMRA	24	804	305
Reverse	5′-agtccactggcgtcttcac-3′	19	831	306

[1030]

TABLE AMB
General_screening_panel_v1.4
	Rel.		Rel.
	Exp. (%)		Exp.(%)
	Ag4439,		Ag4439,
	Run		Run
Tissue Name	220005588	Tissue Name	220005588
Adipose	4.5	Renal Ca. TK-10	27.5
Melanoma*	54.7	Bladder	10.7
Hs688(A).T
Melanoma*	61.6	Gastric Ca.	22.1
Hs688(B).T		(liver met.)
		NCI-N87
Melanoma* M14	65.5	Gastric Ca.	71.2
		KATO III
Melanoma*	71.2	Colon ca. SW-948	18.9
LOXIMVI
Melanoma*	70.7	Colon Ca. SW480	88.9
SK-MEL-5
Squamous cell	26.6	Colon ca.*	38.7
carcinoma SCC-4		(SW480 met)
		SW620
Testis Pool	4.9	Colon ca. HT29	32.8
Prostate ca.*	46.0	Colon ca. HCT-116	70.7
(bone met) PC-3
Prostate Pool	3.3	Colon ca. CaCo-2	49.3
Placenta	3.9	Colon cancer tissue	25.0
Uterus Pool	2.9	Colon ca. SW1116	9.6
Ovarian ca. OVCAR-3	46.0	Colon ca. Colo-205	18.6
Ovarian ca. SK-OV-3	36.9	Colon ca. SW-48	8.3
Ovarian ca. OVCAR-4	23.5	Colon Pool	5.5
Ovarian ca. OVCAR-5	30.8	Small Intestine Pool	3.2
Ovarian ca. IGROV-1	45.4	Stomach Pool	3.3
Ovarian ca. OVCAR-8	37.6	Bone Marrow Pool	3.0
Ovary	3.9	Fetal Heart	22.8
Breast ca. MCF-7	38.4	Heart Pool	11.0
Breast ca.	55.5	Lymph Node Pool	6.6
MDA-MB-231
Breast ca. BT 549	89.5	Fetal Skeletal	22.2
		Muscle
Breast ca. T47D	60.3	Skeletal Muscle	77.4
		Pool
Breast ca. MDA-N	38.4	Spleen Pool	2.8
Breast Pool	5.5	Thymus Pool	4.8
Trachea	8.2	CNS cancer	64.6
		(glio/astro) U87-MG
Lung	1.1	CNS cancer	100.0
		(gilo/astro)
		U-118-MG
Fetal Lung	11.0	CNS cancer	35.6
		(neuro;met)
		SK-N-AS
Lung ca. NCI-N417	10.2	CNS cancer	40.6
		(astro) SF-539
Lung ca. LX-1	47.3	CNS cancer	74.2
		(astro) SNB-75
Lung Ca. NCI-H146	30.1	CNS cancer	43.2
		(glio) SNB-19
Lung Ca. SHP-77	16.4	CNS cancer	97.3
		(glio) SF-295
Lung Ca. A549	75.8	Brain (Amygdala)	8.2
		Pool
Lung ca. NCI-H526	13.1	Brain (cerebellum)	27.4
Lung ca. NCI-H23	45.1	Brain (fetal)	11.3
Lung ca. NCI-H460	30.8	Brain	10.4
		(Hippocampus) Pool
Lung ca. HOP-62	53.2	Cerebral Cortex	15.5
		Pool
Lung ca. NCI-H522	20.6	Brain	14.1
		(Substantia nigra)
		Pool
Liver	3.0	Brain (Thalamus)	14.6
		Pool
Fetal Liver	13.2	Brain (whole)	27.7
Liver ca. HepG2	29.7	Spinal Cord Pool	9.4
Kidney Pool	6.0	Adrenal Gland	8.4
Fetal Kidney	9.9	Pituitary gland Pool	2.2
Renal ca. 786-0	42.3	Salivary Gland	6.8
Renal ca. A498	19.8	Thyroid (female)	3.3
Renal ca. ACHN	46.0	Pancreatic ca.	27.2
		CAPAN2
Renal ca. UO-31	43.8	Pancreas Pool	6.9

[1031]

TABLE AME
HASS Panel v1.0
		Rel.	Rel.
		Exp. (%)	Exp. (%)
		Ag4439,	Ag4439,
		Run	Run
	Tissue Name	248170242	255473892
	MCF-7 C1	20.4	17.0
	MCF-7 C2	27.0	15.0
	MCF-7 C3	12.4	9.8
	MCF-7 C4	27.9	23.2
	MCF-7 C5	21.0	15.6
	MCF-7 C6	28.7	21.2
	MCF-7 C7	97.3	68.8
	MCF-7 C9	80.7	70.2
	MCF-7 C1O	24.5	18.3
	MCF-7 C11	3.1	2.7
	MCF-7 C12	16.8	13.8
	MCF-7 C13	79.6	71.7
	MCF-7 C15	34.6	27.4
	MCF-7 C16	23.2	19.2
	MCF-7 C17	13.6	10.1
	T24 D1	16.5	14.5
	T24 D2	37.1	35.4
	T24 D3	33.2	25.3
	T24 D4	64.6	43.2
	T24 D5	32.5	24.5
	T24 D6	39.2	26.1
	T24 D7	54.0	45.7
	T24 D9	14.5	10.2
	T24 D10	26.6	24.3
	T24 D11	10.3	9.0
	T24 D12	18.8	18.7
	T24 D13	10.7	11.1
	T24 D15	9.9	9.8
	T24 D16	4.3	4.6
	T24 D17	7.0	6.6
	CAPaN B1	18.8	14.3
	CAPaN B2	14.7	13.9
	CAPaN B3	5.0	4.2
	CAPaN B4	11.7	13.4
	CAPaN B5	15.5	11.7
	CAPaN B6	16.6	15.3
	CAPaN B7	31.6	36.1
	CAPaN B8	46.3	46.3
	CAPaN B9	63.3	62.0
	CAPaN B1O	21.8	22.2
	CAPaN B11	17.4	15.5
	CAPaN B12	19.5	18.6
	CAPaN B13	40.1	33.0
	CAPaN B14	40.9	37.1
	CAPaN B15	47.3	49.3
	CAPaN B16	15.0	15.5
	CAPaN B17	21.3	17.7
	U87-MG F1 (B)	32.3	21.6
	U87-MG F2	7.1	7.0
	U87-MG F3	6.9	6.1
	U87-MG F4	13.2	14.7
	U87-MG F5	49.3	48.6
	U87-MG F6	32.1	38.7
	U87-MG F7	64.6	74.2
	U87-MG F8	38.2	42.0
	U87-MG F9	53.6	54.7
	U87-MG F10	42.3	41.2
	U87-MG F11	27.9	31.4
	U87-MG F12	42.9	43.2
	U87-MG F13	100.0	100.0
	U87-MG F14	57.4	59.5
	U87-MG F15	84.7	95.9
	U87-MG F16	33.2	37.6
	U87-MG F17	48.6	45.1
	LnCAP A1	16.6	16.3
	LnCAP A2	16.3	17.6
	LnCAP A3	11.3	11.4
	LnCAP A4	33.7	30.1
	LnCAP A5	18.2	15.9
	LnCAP A6	18.6	16.3
	LnCAP A7	89.5	79.0
	LnCAP A8	69.3	70.2
	LnCAP A9	65.1	57.8
	LnCAP A10	22.2	20.3
	LnCAP A11	14.1	12.9
	LnCAP A12	5.0	4.6
	LnCAP A13	27.2	24.3
	LnCAP A14	25.9	17.4
	LnCAP A15	19.9	16.4
	LnCAP A16	25.5	23.8
	LnCAP A17	21.6	6.5
	Primary Astrocytes	25.9	17.7
	Primary Renal Proximal	16.3	13.5
	Tubule Epithelial
	cell A2
	Primary melanocytes A5	4.3	3.1
	126443 - 341 medullo	0.9	0.7
	126444 - 487 medullo	28.7	27.0
	126445 - 425 medullo	6.1	5.8
	126446 - 690 medullo	14.2	11.4
	126447 - 54 adult glioma	24.8	21.5
	126448 - 245 adult glioma	17.8	17.9
	126449 - 317 adult glioma	22.1	21.5
	126450 - 212 glioma	18.0	15.2
	126451 - 456 glioma	27.7	24.0

[1032]

TABLE AMF
Panel 1.2
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	GAPDH		GAPDH
	(HUMAN),		(HUMAN),
	Run		Run
Tissue Name	138249512	Tissue Name	138249512
Endothelial cells	4.6	Renal ca. 786-0	2.3
Heart (Fetal)	6.2	Renal ca. A498	5.0
Pancreas	0.1	Renal ca. RXF 393	3.8
Pancreatic ca.	2.0	Renal ca. ACHN	7.3
CAPAN 2
Adrenal Gland	4.4	Renal ca. UO-31	5.1
Thyroid	0.3	Renal ca. TK-10	5.3
Salivary gland	1.9	Liver	2.0
Pituitary gland	0.1	Liver (fetal)	1.5
Brain (fetal)	0.1	Liver ca. (hepatoblast)	17.1
		HepG2
Brain (whole)	1.0	Lung	0.1
Brain (amygdala)	2.1	Lung (fetal)	0.1
Brain	0.6	Lung ca. (small cell)	11.1
(cerebellum)		LX-1
Brain	4.1	Lung ca. (small cell)	6.5
(hippocampus)		NCI-H69
Brain (thalamus)	3.5	Lung ca. (s. cell var.)	0.0
		SHP-77
Cerebral Cortex	9.9	Lung ca. (large cell)	0.0
		NCI-H460
Spinal cord	0.4	Lung ca. (non-sm. cell)	13.6
		A549
glio/astro	4.9	Lung ca. (non-s. cell)	8.5
U87-MG		NCI-H23
glio/astro	8.2	Lung ca. (non-s. cell)	27.9
U-118-MG		HOP-62
astrocytoma	2.9	Lung ca. (non-s. cl)	15.8
SW1783		NCI-H522
neuro*; met	6.5	Lung ca. (squam.)	4.2
SK-N-AS		SW 900
astrocytoma	3.5	Lung ca. (squam.)	11.5
SF-539		NCI-H596
astrocytoma	1.9	Mammary gland	0.4
SNB-75
glioma SNB-19	2.6	Breast ca.* (pl. ef)	3.0
		MCF-7
glioma U251	2.4	Breast ca.* (pl. ef)	2.8
		MDA-MB-231
glioma SF-295	4.4	Breast ca.* (pl. ef)	1.4
		T47D
Heart	22.2	Breast ca. BT-549	3.4
Skeletal Muscle	100.0	Breast ca. MDA-N	6.0
Bone marrow	1.0	Ovary	2.6
Thymus	0.3	Ovarian ca. OVCAR-3	9.1
Spleen	0.5	Ovarian ca. OVCAR-4	10.9
Lymph node	0.1	Ovarian ca. OVCAR-5	11.4
Colorectal Tissue	0.1	Ovarian ca. OVCAR-8	7.3
Stomach	0.2	Ovarian ca. IGROV-1	12.5
Small intestine	1.8	Ovarian ca. (ascites)	7.7
		SK-OV-3
Colon ca. SW480	5.4	Uterus	0.6
Colon ca.*	9.0	Placenta	0.3
SW620
(SW480 met)
Colon Ca.	4.2	Prostate	1.8
HT29
Colon Ca.	0.0	Prostate ca.*	0.0
HCT-116		(bone met) PC-3
Colon Ca.	1.8	Testis	0.1
CaCo-2
Colon ca.	1.1	Melanoma Hs688(A).T	1.5
Tissue
(ODO3866)
Colon Ca.	19.1	Melanoma* (met)	2.1
HCC-2998		Hs688(B).T
Gastric ca.*	3.3	Melanoma UACC-62	24.8
(liver met)
NCI-N87
Bladder	1.7	Melanoma M14	7.6
Trachea	0.1	Melanoma LOX IMVI	0.0
Kidney	7.0	Melanoma* (met)	8.2
		SK-MEL-5
Kidney (fetal)	0.8

[1033]

TABLE AMG
Panel 4D
	Rel.	Rel.
	Exp. (%)	Exp. (%)
	GAPDH(HUMAN),	GAPDH(HUMAN),
	Run	Run
Tissue Name	142890204	145267296
Secondary Th1 act	16.0	29.7
Secondary Th2 act	10.8	16.6
Secondary Tr1 act	14.1	19.3
Secondary Th1	2.7	5.1
rest
Secondary Th2	4.4	8.5
rest
Secondary Tr1	4.5	5.5
rest
Primary Th1 act	21.6	41.5
Primary Th2 act	18.4	39.2
Primary Tr1 act	29.3	59.5
Primary Th1 rest	34.6	42.9
Primary Th2 rest	18.6	25.3
Primary Tr1 rest	16.8	28.3
CD45RA CD4 lymphocyte	19.2	32.3
act
CD45RO CD4 lymphocyte	23.5	37.4
act
CD8 lymphocyte	22.7	30.4
act
Secondary CD8	23.0	34.4
lymphocyte rest
Secondary CD8	20.6	36.1
lymphocyte act
CD4 lymphocyte	0.7	0.9
none
2ry Th1/Th2/Tr1_anti-	12.4	20.3
CD95 CH11
LAK cells rest	8.7	15.2
LAK cells IL-2	13.7	19.2
LAK cells IL-	17.8	27.4
2 + IL-12
LAK cells IL-	25.9	33.0
2 + IFN gamma
LAK cells IL-2 +	18.6	21.8
IL-18
LAK cells	15.9	30.6
PMA/ionomycin
NK Cells IL-2 rest	9.8	10.8
Two Way MLR 3	2.7	4.0
day
Two Way MLR 5	9.7	10.5
day
Two Way MLR 7	7.0	9.2
day
PBMC rest	1.1	1.4
PBMC PWM	2.3	2.0
PBMC PHA-L	20.6	43.2
Ramos (B cell)	15.0	36.6
none
Ramos (B cell)	41.8	60.3
ionomycin
B lymphocytes	51.1	65.1
PWM
B lymphocytes	5.8	9.2
CD40L and IL-4
EOL-1 dbcAMP	7.7	9.9
EOL-1 dbcAMP	5.7	8.2
PMA/ionomycin
Dendritic cells	9.5	15.3
none
Dendritic cells	9.0	9.9
LPS
Dendritic cells	7.1	10.2
anti-CD40
Monocytes rest	7.3	9.7
Monocytes LPS	3.4	7.9
Macrophages rest	14.3	30.6
Macrophages LPS	7.9	23.3
HUVEC none	17.4	22.4
HUVEC starved	26.4	42.0
HUVEC IL-1beta	11.2	8.4
HUVEC IFN gamma	15.9	23.8
HUVEC TNF alpha +	18.0	10.4
IFN gamma
HUVEC TNF alpha +	18.2	23.0
IL4
HUVEC IL-11	5.9	6.5
Lung Microvascular EC	7.5	10.8
none
Lung Microvascular EC	6.6	6.7
TNFalpha + IL-1beta
Microvascular Dermal EC	19.8	41.5
none
Microsvasular Dermal EC	10.5	24.7
TNFalpha + IL-1beta
Bronchial epithelium	24.8	34.2
TNFalpha + IL1beta
Small airway epithelium	17.0	22.1
none
Small airway epithelium	73.7	100.0
TNFalpha + IL-1beta
Coronery artery	22.2	22.4
SMC rest
Coronery artery SMC	15.2	18.0
TNFalpha + IL-1beta
Astrocytes rest	9.5	7.3
Astrocytes	6.7	9.6
TNFalpha + IL-1beta
KU-812 (Basophil) rest	0.2	0.3
KU-812 (Basophil)	1.0	0.9
PMA/ionomycin
CCD1106 (Keratinocytes)	29.1	31.4
none
CCD1106 (Keratinocytes)	100.0	22.1
TNFalpha + IL-1beta
Liver cirrhosis	1.4	2.5
Lupus kidney	0.6	1.7
NCI-H292 none	18.0	20.0
NCI-H292 IL-4	24.0	28.5
NCI-H292 IL-9	28.5	30.8
NCI-H292 IL-13	17.0	27.5
NCI-H292 IFN gamma	17.3	18.4
HPAEC none	13.4	21.6
HPAEC TNF alpha +	15.4	24.0
IL-1beta
Lung fibroblast none	14.2	23.8
Lung fibroblast TNF	12.9	12.2
alpha + IL-1 beta
Lung fibroblast IL-4	32.1	35.1
Lung fibroblast IL-9	30.6	31.9
Lung fibroblast IL-13	18.9	51.1
Lung fibroblast IFN	32.5	44.8
gamma
Dermal fibroblast	19.9	29.3
CCD1070 rest
Dermal fibroblast	66.0	61.1
CCD1070 TNF alpha
Dermal fibroblast	16.0	23.0
CCD1070 IL-1 beta
Dermal fibroblast IFN	7.2	7.2
gamma
Dermal fibroblast IL-4	11.7	16.2
IBD Colitis 2	0.2	0.4
IBD Crohn's	0.7	0.7
Colon	5.6	5.1
Lung	4.4	5.0
Thymus	4.9	10.6
Kidney	6.9	6.2

[1034]

TABLE AMH
Panel 5 Islet
		Rel.	Rel.
		Exp. (%)	Exp. (%)
		Ag4439,	Ag4439,
		Run	Run
	Tissue Name	242449345	244646283
	97457_Patient-	5.4	5.5
	02go_adipose
	97476_Patient-	14.8	15.2
	07sk_skeletal
	muscle
	97477_Patient-	6.4	5.1
	07ut_uterus
	97478_Patient-	4.4	4.0
	07pl_placenta
	99167_Bayer	51.8	50.0
	Patient 1
	97482_Patient-	6.2	5.3
	08ut_uterus
	97483_Patient-	3.3	2.5
	08pl_placenta
	97486_Patient-	15.5	8.4
	09sk_skeletal
	muscle
	97487_Patient-	7.7	4.4
	09ut_uterus
	97488_Patient-	2.3	1.7
	09pl_placenta
	97492_Patient-	11.2	8.8
	10ut_uterus
	97493_Patient-	6.2	4.3
	10pl_placenta
	97495_Patient-	3.3	2.2
	11go_adipose
	97496_Patient-	81.8	55.1
	11sk_skeletal
	muscle
	97497_Patient-	10.5	8.0
	11ut_uterus
	97498_Patient-	1.5	1.0
	11p1_placenta
	97500_Patient-	3.0	4.2
	12go_adipose
	97501_Patient-	100.0	100.0
	12sk_skeletal
	muscle
	97502_Patient-	11.4	8.4
	12ut_uterus
	97503_Patient-	1.6	1.1
	12pl_placenta
	94721_Donor 2 U -	29.3	31.2
	A_Mesenchymal
	Stem Cells
	94722_Donor 2 U -	13.4	16.2
	B_Mesenchymal
	Stem Cells
	94723_Donor 2 U -	24.7	27.9
	C_Mesenchymal
	Stem Cells
	94709_Donor 2	28.5	32.8
	AM - A_adipose
	94710_Donor 2	20.3	11.9
	AM - B_adipose
	94711_Donor 2	13.7	12.9
	AM - C_adipose
	94712_Donor 2	31.9	27.2
	AD - A_adipose
	94713_Donor 2	36.9	28.3
	AD - B_adipose
	94714_Donor 2	39.8	33.4
	AD - C_adipose
	94742_Donor 3	12.4	11.3
	U - A_Mesenchymal
	Stem Cells
	94743_Donor 3	22.5	18.9
	U - B_Mesenchymal
	Stem Cells
	94730_Donor 3	29.9	29.1
	AM - A_adipose
	94731_Donor 3	16.3	15.3
	AM - B_adipose
	94732_Donor 3	16.7	17.0
	AM - C_adipose
	94733_Donor 3	55.9	49.3
	AD - A_adipose
	94734_Donor 3	12.7	12.7
	AD - B_adipose
	94735_Donor 3	45.4	33.7
	AD - C_adipose
	77138_Liver—	45.1	30.8
	HepG2untreated
	73556_Heart_Cardiac	24.5	16.2
	stromal cells (primary)
	81735_Small Intestine	11.8	8.4
	72409_Kidney_Proximal	7.6	7.9
	Convoluted Tubule
	82685_Small	0.8	0.6
	intestine_Duodenum
	90650_Adrenal—	3.3	2.1
	Adrenocortical adenoma
	72410_Kidney_HRCE	48.6	33.0
	72411_Kidney_HRE	26.4	20.2
	73139_Uterus_Uterine	16.4	11.4
	smooth muscle cells

[1035]

TABLE AMI
general oncology screening panel_v_2.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4439,		Ag4339,
	Run		Run
Tissue Name	268672131	Tissue Name	268672131
Colon cancer 1	19.9	Bladder cancer	0.5
		NAT 2
Colon cancer NAT 1	6.7	Bladder cancer	0.8
		NAT 3
Colon cancer 2	53.6	Bladder cancer	4.2
		NAT 4
Colon cancer NAT 2	11.7	Prostate	15.6
		adenocarcinoma 1
Colon cancer 3	49.0	Prostate	2.1
		adenocarcinoma 2
Colon cancer NAT 3	14.0	Prostate	5.3
		adenocarcinoma 3
Colon malignant cancer 4	77.4	Prostate	20.9
		adenocarcinoma 4
Colon normal adjacent	7.9	Prostate cancer	2.8
tissue 4		NAT 5
Lung cancer 1	29.9	Prostate	1.9
		adenocarcinoma 6
Lung NAT 1	1.2	Prostate	2.9
		adenocarcinoma 7
Lung cancer 2	50.3	Prostate	0.8
		adenocarcinoma 8
Lung NAT 2	0.6	Prostate	11.8
		adenocarcinoma 9
Squamous cell	35.4	Prostate cancer	1.6
carcinoma 3		NAT 10
Lung NAT 3	0.4	Kidney cancer 1	16.2
metastatic melanoma 1	8.4	Kidney NAT 1	2.9
Melanoma 2	6.5	Kidney cancer 2	100.0
Melanoma 3	3.3	NAT 2	7.9
metastatic melanoma 4	18.7	Kidney cancer 3	20.4
metastatic melanoma 5	18.3	Kidney NAT 3	3.3
Bladder cancer 1	2.3	Kidney cancer 4	24.5
Bladder cancer NAT 1	0.0	Kidney NAT 4	6.2
Bladder cancer 2	5.8

[1036] General_screening_panel_v1.4 Summary: Ag4439 Expression of this gene is highest in a CNS cancer cell line (CT=19.2). The CG55814-02 gene is expressed at very high levels in all of the tissues on this panel. However, higher expression is associated with cancer cell lines and skeletal muscle. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of cancer.

[1037] Among tissues with metabolic or endocrine function, this gene is expressed at high levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[1038] In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[1039] The CG55814-02 gene encodes a splice variant of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). GAPDH is a well-studied glycolytic enzyme that plays a key role in energy metabolism. GAPDH catalyzes the conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate in the glycolytic pathway. As part of the conversion, GAPDH converts NAD+ to the high-energy electron carrier NADH. In recent years, GAPDH has been shown to contribute to a number of diverse cellular functions unrelated to glycolysis [reviewed in Tatton et al., J Neural Transm Suppl. 2000;(60):77-100, PMID: 11205159]. Normative functions of GAPDH now include nuclear RNA export, DNA replication, DNA repair, exocytotic membrane fusion, cytoskeletal organization and phosphotransferase activity. Pathologically, GAPDH has been implicated in apoptosis, neurodegenerative disease, prostate cancer and viral pathogenesis. Most recently, it has been shown that GAPDH is a target for deprenyl related compounds and may contribute to the neuroprotection offered by those compounds [Carlile et al., Mol Pharmacol. January 2000;57(1):2-12, PMID: 10617673].

[1040] HASS Panel v1.0 Summary: Ag4439

[1041] This gene is expressed at a high to very high level in all the cell lines on this panel with a maximum level in U87-MG cells that are subjected to no oxygen and an acidic environment for 24 hours in the presence of serum (CT=17.49, 18.26). There is good concordance between the two runs on this panel. The expression of this gene is induced in LnCAP, Capan and MCF7 by a lack of oxygen in the presence and absence of serum. Expression is also increased in U-87 MG cells in the absence of serum for 72 hours compared to the control cells that are in serum containing media. This suggests that expression of this, gene may be a marker for regions of prostate, pancreatic, brain and breast tumors that are deprived of oxygen or nutrients.

[1042] Additionally, this gene is expressed in all the medulloblastomas and gliomas that are on this panel.

[1043] Panel 1.2 Summary: GAPDH(HUMAN) Expression of this gene is highest in skeletal muscle (CT=15.7). The CG55814-02 gene is expressed at very high levels in all of the tissues on this panel. These results are consistent with what is observed in Panel 1.4. See Panel 1.4 for further discussion of this gene in treatment of human disease.

[1044] Panel 4D Summary: GAPDH(HUMAN) Results from two experiments using the same probe-primer set are in good agreement. This gene is expressed at very high levels in a wide range of cell types of significance in the immune response in health and disease, including T-cells, B-cells, endothelial cells, macrophages, monocytes, eosinophils, basophils, neutrophils, peripheral blood mononuclear cells, lung and skin epithelial cells, lung and skin fibroblast cells, as well as normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in, homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[1045] Panel 5 Islet Summary: Ag4439 Two experiments performed using the same probe-primer set gave results that are in good agreement. Expression of the CG55814-02 gene is highest in skeletal muscle, adipose and pancreatic islets, with moderate expression detected in all other tissues. The CG55814-02 gene encodes a splice variant of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). GAPDH is a well-studied glycolytic enzyme that plays a key role in energy metabolism. GAPDH catalyzes the conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate in the glycolytic pathway. As part of the conversion, GAPDH converts NAD+ to the high-energy electron carrier NADH. Flux through the glycolytic pathway is crucial for glucose-induced insulin secretion. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and Type 2 diabetes.

[1046] general oncology screening panel_v—2.4 Summary: Ag4439 Expression of this gene is highest in a kidney cancer sample (CT=20.1). Throughout this panel, expression of the CG55814-02 gene is higher in tumors than in the corresponding normal tissues. Overexpression of this gene is particularly striking in kidney, lung, and colon tumors. Therefore, expression of this gene may be used as a marker for kidney, lung, and colon cancer. Furthermore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of kidney, lung and colon cancer.

[1047] AN. CG56735-01 and CG56735-02: ADAMTS 7

[1048] Expression of gene CG56735-01 was assessed using the primer-probe sets Ag2430 and Ag4413, described in Tables ANA and ANB. Results of the RTQ-PCR runs are shown in Tables ANC, AND, ANE, ANF, ANG, ANH, ANI, ANJ and ANK.

TABLE ANA
Probe Name Ag2430
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cattggaaagaatggcaaga-3′	20	1209	307
Probe	TET-5′-catgatcatgccatcttactaacagga-3′-TAMRA	27	1231	308
Reverse	5′-tcacatggttcattcttccaa-3′	21	1272	309

[1049]

TABLE ANB
Probe Name Ag4413
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ttggaagaatgaaccatgtga-3′	21	1272	310
Probe	TET-5′-ccccatcagtggaatgtgctctaagt-3′-TAMRA	26	1308	311
Reverse	5′-caagtcctgtgtcctcattgat-3′	22	1348	312

[1050]

TABLE ANC
A1_comprehensive panel_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4413,		Ag4413,
	Run		Run
Tissue Name	251506632	Tissue Name	251506632
110967 COPD-F	5.1	112427 Match	1.4
		Control Psoriasis-F
110980 COPD-F	0.0	112418 Psoriasis-M	3.3
110968 COPD-M	4.2	112723 Match	22.8
		Control Psoriasis-M
110977 COPD-M	0.5	112419 Psoriasis-M	0.7
110989 Emphysema-F	33.2	112424 Match	6.4
		Control Psoriasis-M
110992 Emphysema-F	3.5	112420 Psoriasis-M	7.3
110993 Emphysema-F	7.9	1112425 Match	10.8
		Control Psoriasis-M
110994 Emphysema-F	3.4	104689 (MF) OA	17.1
		Bone-Backus
110995 Emphysema-F	4.0	104690 (MF) Adj	1.5
		“Normal”
		Bone-Backus
110996 Emphysema-F	0.9	104691 (MF) OA	3.6
		Synovium-Backus
110997 Asthma-M	3.0	104692 (BA) OA	0.0
		Cartilage-Backus
111001 Asthma-F	24.1	104694 (BA) OA	3.9
		Bone-Backus
111002 Asthma-F	22.4	104695 (BA) Adj	6.3
		“Normal”
		Bone-Backus
111003 Atopic	71.2	1104696 (BA) OA	16.6
Asthma-F		Synovium-Backus
111004 Atopic	33.4	104700 (SS) OA	2.3
Asthma-F		Bone-Backus
111005 Atopic	38.2	104701 (SS) Adj	4.1
Asthma-F		“Normal”
		Bone-Backus
111006 Atopic	7.9	104702 (SS) OA	60.3
Asthma-F		Synovium-Backus
111417 Allergy-M	1.1	1170919 OA	3.2
		Cartilage Rep7
112347 Allergy-M	0.0	112672 OA Bone5	0.6
112349 Normal	0.0	112673 OA	0.0
Lung-F		Synovium5
112357 Normal	17.6	112674 OA	0.6
Lung-F		Synovial Fluid
		cells5
112354 Normal	0.7	117100 OA	0.5
Lung-M		Cartilage Rep14
112374 Crohns-F	6.3	112756 OA Bone9	20.7
112389 Match Control	0.0	112757 OA
Crohns-F		Synovium9
112375 Crohns-F	5.1	1112758 OA	12.9
		Synovial
		Fluid Cells9
112732 Match Control	0.0	117125 RA	24.3
Crohns-F		Cartilage Rep2
112725 Crohns-M	0.0	1113492 Bone2 RA	1.4
112387 Match Control	0.6	113493 Synovium2	0.0
Crohns-M		RA
112378 Crohns-M	0.0	113494 Syn Fluid	1.0
		Cells RA
112390 Match Control	6.0	113499 Cartilage4	0.0
Crohns-M		RA
112726 Crohns-M	100.0	113500 Bone4 RA	0.0
112731 Match Control	52.1	1113501 Synovium4	0.7
Crohns-M		RA
112380 Ulcer Col-F	29.3	113502 Syn Fluid	1.5
		Cells4 RA
112734 Match Control	0.6	113495 Cartilage3	0.8
Ulcer Col-F		RA
112384 Ulcer Col-F	4.2	113496 Bone3 RA	0.5
112737 Match Control	52.1	113497 Synovium3	0.6
Ulcer Col-F		RA
112386 Ulcer Col-F	0.7	113498 Syn Fluid	10.0
		Cells3 RA
112738 Match Control	0.0	117106 Normal	1.3
Ulcer Col-F		Cartilage Rep20
112381 Ulcer Col-M	0.5	113663	0.1
		Bone3 Normal
112735 Match Control	0.9	113664	0.0
Ulcer Col-M		Synovium3 Normal
112382 Ulcer Col-M	0.0	113665 Syn Fluid	0.0
		Cells3 Normal
112394 Match Control	0.6	117107 Normal	1.3
Ulcer Col-M		Cartilage Rep22
112383 Ulcer Col-M	18.7	113667 Bone4	0.9
		Normal
112736 Match Control	0.0	113668 Synovium4	1.6
Ulcer Col-M		Normal
112423 Psoriasis-F	11.2	113669 Syn Fluid	1.9
		Cells4 Normal

[1051]

TABLE AND
CNS_neurodegeneration_v1.0
		Rel. Exp. (%)	Rel. Exp. (%)
		Ag2430,	Ag4413,
		Run	Run
	Tissue Name	208712834	224505949
	AD 1 Hippo	0.0	0.0
	AD 2 Hippo	15.4	21.6
	AD 3 Hippo	0.0	0.8
	AD 4 Hippo	17.6	27.5
	AD 5 Hippo	13.9	22.5
	AD 6 Hippo	43.2	0.0
	Control 2 Hippo	62.9	85.9
	Control 4 Hippo	0.0	1.6
	Control (Path) 3	3.2	14.5
	Hippo
	AD 1 Temporal Ctx	0.9	0.7
	AD 2 Temporal Ctx	21.9	37.6
	AD 3 Temporal Ctx	0.0	0.0
	AD 4 Temporal Ctx	57.0	97.9
	AD 5 Inf Temporal	69.7	65.1
	Ctx
	AD 5 Sup Temporal	38.2	26.2
	Ctx
	AD 6 Inf Temporal	100.0	100.0
	Ctx
	AD 6 Sup Temporal Ctx	36.6	37.6
	Control 1 Temporal	0.0	0.8
	Ctx
	Control 2 Temporal	36.6	45.7
	Ctx
	Control 3 Temporal	9.3	12.5
	Ctx
	Control 3 Temporal	0.0	1.4
	Ctx
	Control (Path) 1	18.0	28.1
	Temporal Ctx
	Control (Path) 2	5.1	0.0
	Temporal Ctx
	Control (Path) 3	2.2	3.0
	Temporal Ctx
	Control (Path) 4	1.1	4.0
	Temporal Ctx
	AD 1 Occipital Ctx	0.7	0.0
	AD 2 Occipital Ctx	0.0	0.0
	(Missing)
	AD 3 Occipital Ctx	0.0	0.0
	AD 4 Occipital Ctx	52.5	94.0
	AD 5 Occipital Ctx	27.7	25.5
	AD 6 Occipital Ctx	24.0	27.7
	Control 1 Occipital	0.0	0.0
	Ctx
	Control 2 Occipital	52.1	66.0
	Ctx
	Control 3 Occipital	3.1	11.1
	Ctx
	Control 4 Occipital	0.0	0.0
	Ctx
	Control (Path) 1	59.9	73.2
	Occipital Ctx
	Control (Path) 2	6.6	10.1
	Occipital Ctx
	Control (Path) 3	5.4	4.7
	Occipital Ctx
	Control (Path) 4	0.0	0.0
	Occipital Ctx
	Control 1 Parietal Ctx	0.0	0.0
	Control 2 Parietal	37.6	38.4
	Ctx
	Control 3 Parietal	6.3	6.6
	Ctx
	Control (Path) 1	19.5	26.1
	Parietal Ctx
	Control (Path) 2	7.2	9.1
	Parietal Ctx
	Control (Path) 3	0.0	4.6
	Parietal Ctx
	Control (Path) 4	0.0	0.9
	Parietal Ctx

[1052]

TABLE ANE
General_screening_panel_v1.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4413,		Ag4413,
	Run		Run
Tissue Name	219923153	Tissue Name	219923153
Adipose	7.2	Renal ca. TK-10	0.0
Melanoma* Hs688(A).T	0.0	Bladder	0.2
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.) NCI-N87	0.0
Melanoma* M14	0.0	Gastric ca. KATO III	0.5
Melanoma* LOXIMVI	37.4	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	0.0
Squamous cell carcinoma SCC-	0.0	Colon ca.* (SW480 met) SW620	49.0
1
Testis Pool	1.8	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.0	Colon ca. HCT-116	0.0
Prostate Pool	1.3	Colon ca. CaCo-2	3.0
Placenta	19.5	Colon cancer tissue	2.6
Uterus Pool	0.9	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.0	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.2	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	11.2
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	1.7
Ovarian ca. IGROV-1	0.1	Stomach Pool	6.3
Ovarian ca. OVCAR-8	3.0	Bone Marrow Pool	2.7
Ovary	19.2	Fetal Heat	0.3
Breast ca. MCF-7	0.0	Heart Pool	1.5
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	20.3
Breast ca. BT 549	1.1	Fetal Skeletal Muscle	3.0
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	0.0
Breast Pool	11.7	Thymus Pool	8.4
Trachea	0.9	CNS cancer (glio/astro) U87-MG	39.0
Lung	0.6	CNS cancer (glio/astro) U-118-	1.8
		MG
Fetal Lung	0.6	CNS cancer (neuro;met) SK-N-AS	0.2
Lung ca. NCI-N417	0.0	CNS cancer (astro) SK-539	0.0
Lung ca. LX-1	9.7	CNS cancer (astro) SNB-75	0.7
Lung ca. NCI-H146	3.1	CNS cancer (glio) SNB-19	0.2
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	1.3
Lung ca. A549	0.0	Brain (Amygdala) Pool	4.0
Lung ca. NCI-H526	5.4	Brain (cerebellum)	100.0
Lung ca. NCI-H23	0.9	Brain (fetal)	2.7
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	2.0
Lung ca. HOP-62	0.4	Cerebral Cortex Pool	4.3
Lung ca. NCI-H522	0.0	Brain (Substantia nigra) Pool	5.5
Liver	0.0	Brain (Thalamus) Pool	8.7
Fetal Liver	0.7	Brain (whole)	11.8
Liver ca. HepG2	0.2	Spinal Cord Pool	8.0
Kidney Pool	2.1	Adrenal Gland	0.0
Fetal Kidney	17.1	Pituitary gland Pool	3.2
Renal ca. 786-0	0.0	Salivary Gland	6.8
Renal ca. A498	0.0	Thyroid (female)	0.3
Renal ca. ACHN	3.1	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	30.1	Pancreas Pool	8.2

[1053]

TABLE ANF
Oncology_cell_line_screening_panel_v3.2
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag2430,		Ag2430,
	Run		Run
Tissue Name	258381230	Tissue Name	258381230
94905_Daoy_Medulloblastoma/Cerebellum_sscDNA	0.0	94954_Ca Ski_Cervical epidermoid	0.0
		carcinoma (metastasis)_sscDNA
94906_TE671_Medulloblastom/Cerebellum—	0.0	94955_ES-2_Ovarian clear cell	0.0
sscDNA		carcinoma_sscDNA
94907_D283	0.0	94957_Ramos/6h stim_Stimulated with	0.0
Med_Medulloblastoma/Cerebellum_sscDNA		PMA/ionomycin 6h_sscDNA
94908_PFSK-1_Primitive	0.0	94958_Ramos/14h stim_Stimulated with	0.0
Neuroectodermal/Cerebellum_sscDNA		PMA/ionomycin 14h_sscDNA
94909_XF-498_CNS_sscDNA	0.0	94962_MEG-01_Chronic myelogenous	0.0
		leukemia (megokaryoblast)_sscDNA
94910_SNB-78_CNS/glioma_sscDNA	0.0	94963_Raji_Burkitt's lymphoma_sscDNA	0.0
94911_SF-268_CNS/glioblastoma_sscDNA	0.0	94964_Daudi_Burkitt's lymphoma_sscDNA	0.0
94912_T98G_Glioblastoma_sscDNA	0.0	94965_U266_B-cell	0.0
		plasmacytoma/myeloma_sscDNA
96776_SK-N-SH_Neuroblastoma	0.0	94968_CA46_Burkitt's lymphoma_sscDNA	0.0
(metastasis)_sscDNA
94913_SF-295_CNS/glioblastoma_sscDNA	0.0	94970_RL_non-Hodgkin's B-cell	0.0
		lymphoma_sscDNA
132565_NT2 pool_sscDNA	0.1	94972_JM1_pre-B-cell	0.0
		lymphoma/leukemia_sscDNA
94914_Cerebellum_sscDNA	57.8	94973_Jurkat_T cell leukemia_sscDNA	0.0
96777_Cerebellum_sscDNA	25.5	94974_TF-1_Erythroleukemia_sscDNA	0.0
94916_NCI-H292_Mucoepidermoid lung	0.0	94975_HUT 78_T-cell lymphoma_sscDNA	0.0
carcinoma_sscDNA
94917_DMA-114_Small cell lung cancer_sscDNA	17.9	94977_U937_Histiocytic	0.0
		lymphoma_sscDNA
94918_DMA-79_Small cell lung	100.0	94980_KU-812_Myelogenous	0.0
cancer/neuroendocrine_sscDNA		leukemia_sscDNA
94919_NCI-H146_Small cell lung	2.9	94981_769-P_Clear cell renal	0.0
cancer/neuroendocrine_sscDNA		carcinoma_sscDNA
94920_NCI-H526_Small cell lung	10.9	94983_Caki-2_Clear cell renal	0.0
cancer/neuroendocrine_sscDNA		carcinoma_sscDNA
94921_NCI-N417_Small cell lung	0.0	94984_SW 839_Clear cell renal	0.0
cancer/neuroendocrine_sscDNA		carcinoma_sscDNA
94923_NCI-H82_Small cell lung	0.0	94986_G401-Wilms' tumor_sscDNA	0.0
cancer/neuroendocrine_sscDNA
94924_NCI-H157_Squamous cell lung cancer	0.0	126768_293 cells_sscDNA	0.0
(metastasis)_sscDNA
94925_NCI-H1155_Large cell lung	0.0	94987_Hs766T_Pancreatic carcinoma (LN	0.0
cancer/neuroendocrine_sscDNA		metastasis)_sscDNA
94926_NCI-H1299_Large cell lung	0.0	94988_CAPAN-1_Pancreatic	0.0
cancer/neuroendocrine_sscDNA		adenocarcinoma (liver metastasis)_sscDNA
94927_NCI-H727_Lung carcinoid_sscDNA	0.3	94989_SU86.86_Pancreatic carcinoma (liver	0.0
		metastasis)_sscDNA
94928_NCI-UMC-11_Lung carcinoid_sscDNA	0.0	94990_BxPC-3_Pancreatic	0.0
		adenocarcinoma_sscDNA
94929_LX-1_Small cell lung cancer_sscDNA	3.8	94991_HPAC_Pancreatic	0.0
		adenocarcinoma_sscDNA
94930_Colo-205_Colon cancer_sscDNA	0.0	94992_MIA PaCa-2_Pancreatic	0.0
		carcinoma_sscDNA
94931_KM12_Colon cancer_sscDNA	0.0	94993_CFPAC-1_Pancreatic ductal	0.0
		adenocarcinoma_sscDNA
94932_KM20L2_Colon cancer_sscDNA	0.0	94994_PANC-1_Pancreatic epithelioid	0.0
		ductal carcinoma_sscDNA
94933_NCI-H716_Colon cancer_sscDNA	0.0	94996_T24_Bladder carcinma (transitional	0.0
		cell)_sscDNA
94935_SW-48_Colon adenocarcinoma_sscDNA	0.0	94997_5637_Bladder carcinoma_sscDNA	0.0
94936_SW1116_Colon adenocarcinoma_sscDNA	0.0	94998_HT-1197_Bladder	0.0
		carcinoma_sscDNA
94937_LS 174T_Colon adenocarcinoma_sscDNA	0.0	94999_UM-UC-3_Bladder carcinma	0.0
		(transitional cell)_sscDNA
94938_SW-948_Colon adenocarcinoma_sscDNA	0.0	95000_A204_Rhabdomyosarcoma_sscDNA	0.4
94939_SW-480_Colon adenocarcinoma_sscDNA	0.0	95001_HT-1080_Fibrosarcoma_sscDNA	0.2
94940_NCI-SNU-5_Gastric carcinoma_sscDNA	0.0	95002_MG-63_Osteosarcoma	0.0
		(bone)_sscDNA
112197_KATO III_Stomach_sscDNA	0.0	95003_SK-LMS-1_Leiomyosarcoma	0.0
		(vulva)_sscDNA
94943_NCI-SNU-16_Gastric carcinoma_sscDNA	0.0	95004_SJRH30_Rhabdomyosarcoma (met	0.0
		to bone marrow)_sscDNA
94944_NCI-SNU-1_Gastric carcinoma_sscDNA	0.0	95005_A431_Epidermoid	0.0
		carcinoma_sscDNA
94946_RF-1_Gastric adenocarcinoma_sscDNA	0.0	95007_WM266-4_Melanoma_sscDNA	0.0
94947_RF-48_Gastric adenocarcinoma_sscDNA	0.0	112195_DU 145_Prostate_sscDNA	0.0
96778_MKN-45_Gastric carcinoma_sscDNA	0.0	95012_MDA-MB-468_Breast	0.0
		adenocarcinoma_sscDNA
94949_NCI-N87_Gastric carcinoma_sscDNA	0.0	112196_SSC-4_Tongue_sscDNA	0.0
94951_OVCAR-5_Ovarian carcinoma_sscDNA	0.0	112194_SSC-9_Tongue_sscDNA	0.0
94952_RL95-2_Uterine carcinoma_sscDNA	0.0	112191_SSC-15_Tongue_sscDNA	0.0
94953_HelaS3_Cervical adenocarcinoma_sscDNA	0.0	95017_CAL 27_Squamous cell carcinoma	0.0
		of tongue_sscDNA

[1054]

TABLE ANG
Panel 1.3D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag2430,		Ag2430,
	Run		Run
Tissue Name	159505456	Tissue Name	159505456
Liver adenocarcinoma	0.0	Kidney (fetal)	9.3
Pancreas	0.0	Renal ca. 786-0	0.0
Pancreatic ca. CAPAN 2	0.0	Renal ca. A498	0.5
Adrenal gland	1.1	Renal ca. RXF 393	0.0
Thyroid	0.2	Renal ca. ACHN	3.8
Salivary gland	15.0	Renal ca. UO-31	13.9
Pituitary gland	13.2	Renal ca. TK-10	0.0
Brain (fetal)	0.3	Liver	0.0
Brain (whole)	40.9	Liver (fetal)	0.0
Brain (amygdala)	9.7	Liver ca. (hepatoblast) HepG2	0.0
Brain (cerebellum)	100.0	Lung	0.0
Brain (hippocampus)	37.9	Lung (fetal)	2.6
Brain (substantia nigra)	8.0	Lung ca. (small cell) LX-1	9.9
Brain (thalamus)	12.2	Lung ca. (small cell) NCI-H69	29.5
Cerebral Cortex	4.1	Lung ca. (s.cell var.) SHP-77	0.0
Spinal cord	6.4	Lung ca. (large cell)NCI-H460	0.0
glio/astro U87-MG	59.9	Lung ca. (non-sm. cell) A549	0.0
glio/astro U-118-MG	6.7	Lung ca. (non-s.cell) NCI-H23	2.0
astrocytoma SW1783	0.0	Lung ca. (non-s.cell) HOP-62	0.0
neuro*; met SK-N-AS	0.0	Lung ca. (non-s.cl) NCI-H522	0.0
astrocytoma SF-539	0.0	Lung ca. (squam.) SW900	0.0
astrocytoma SNB-75	0.6	Lung ca. (squam.) NCI-H596	0.8
glioma SNB-19	0.3	Mammary gland	30.8
glioma U251	17.8	Breast ca.* (pl.ef) MCF-7	0.0
glioma SF-295	0.5	Breast ca.* (pl.ef) MDA-MB-	0.0
		231
Heart (fetal)	0.0	Breast ca.* (pl.ef) T47D	0.0
Heart	0.0	Breast ca. BT-549	31.9
Skeletal muscle (fetal)	13.5	Breast ca. MDA-N	0.3
Skeletal muscle	0.0	Ovary	32.8
Bone marrow	0.0	Ovarian ca. OVCAR-3	0.0
Thymus	3.1	Ovarian ca. OVCAR-4	0.0
Spleen	0.0	Ovarian ca. OVCAR-5	0.0
Lymph node	0.6	Ovarian ca. OVCAR-8	0.0
Colorectal	0.9	Ovarian ca. IGROV-1	0.2
Stomach	0.0	Ovarian ca.* (ascites) SK-OV-3	0.0
Small intestine	0.3	Uterus	3.0
Colon ca. SW480	0.0	Placenta	47.0
Colon ca.* SW620(SW480 met)	75.3	Prostate	1.4
Colon ca. HT29	0.0	Prostate ca.* (bone met)PC-3	0.0
Colon ca. HCT-116	0.0	Testis	1.2
Colon ca. CaCo-2	2.8	Melanoma Hs688(A).T	0.0
Colon ca. tissue(ODO3866)	5.1	Melanoma* (met) Hs688(B).T	0.0
Colon ca. HCC-2998	0.0	Melanoma UACC-62	0.0
Gastric ca.* (liver met) NCI-N87	0.0	Melanoma M14	0.0
Bladder	1.7	Melanoma LOX IMVI	45.4
Trachea	2.2	Melanoma* (met) SK-MEL-5	0.0
Kidney	0.2	Adipose	18.6

[1055]

TABLE ANH
Panel 2D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag2430,		Ag2430,
	Run		Run
Tissue Name	169505825	Tissue Name	159505825
Normal Colon	15.4	Kidney Margin 8120608	0.6
CC Well to Mod Diff (ODO3866)	12.9	Kidney Cancer 8120613	5.1
CC Margin (ODO3866)	0.0	Kidney Margin 8120614	6.1
CC Gr.2 rectosigmoid (ODO3868)	0.3	Kidney Cancer 9010320	9.7
CC Margin (ODO3868)	3.0	Kidney Margin 9010321	2.7
CC Mod Diff (ODO3920)	5.3	Normal Uterus	23.8
CC Margin (ODO3920)	2.3	Uterus Cancer 064011	25.5
CC Gr.2 ascend colon (ODO3921)	12.7	Normal Thyroid	2.9
CC Margin (ODO3921)	4.6	Thyroid Cancer 064010	23.8
CC from Partial Hepatectomy	0.0	Thyroid Cancer A302152	14.3
(ODO4309) Mets
Liver Margin (ODO4309)	0.0	Thyroid Margin A302153	5.6
Colon mets to lung (ODO4451-01)	0.0	Normal Breast	58.6
Lung Margin (ODO4451-02)	0.0	Breast Cancer (ODO4566)	2.3
Normal Prostate 6546-1	1.0	Breast Cancer (ODO4590-01)	30.6
Prostate Cancer (ODO4410)	1.2	Breast Cancer Mets	17.0
		(ODO4590-03)
Prostate Margin (ODO4410)	47.0	Breast Cancer Metastasis	6.6
		(ODO4655-05)
Prostate Cancer (ODO4720-01)	7.9	Breast Cancer 064006	7.1
Prostate Margin (ODO4720-02)	0.0	Breast Cancer 1024	59.0
Normal Lung 061010	11.4	Breast Cancer 9100266	33.0
Lung Met to Muscle (ODO4286)	1.2	Breast Margin 9100265	26.6
Muscle Margin (ODO4286)	6.8	Breast Cancer A209073	43.8
Lung Malignant Cancer	10.9	Breast Margin A209073	68.3
(ODO3126)
Lung Margin (ODO3126)	2.5	Normal Liver	0.0
Lung Cancer (ODO4404)	2.3	Liver Cancer 064003	0.8
Lung Margin (ODO4404)	24.7	Liver Cancer 1025	0.0
Lung Cancer (ODO4565)	6.9	Liver Cancer 1026	3.0
Lung Margin (ODO4565)	1.2	Liver Cancer 6004-T	0.0
Lung Cancer (ODO4237-01)	100.0	Liver Tissue 6004-N	2.9
Lung Margin (ODO4237-02)	9.8	Liver Cancer 6005-T	0.0
Ocular Mel Met to Liver	0.0	Liver Tissue 6005-N	0.0
(ODO4310)
Liver Margin (ODO4310)	0.0	Normal Bladder	4.8
Melanoma Mets to Lung	1.5	Bladder Cancer 1023	2.5
(ODO4321)
Lung Margin (ODO4321)	0.0	Bladder Cancer A302173	16.3
Normal Kidney	24.7	Bladder Cancer (ODO4718-01)	6.1
Kidney Ca, Nuclear grade 2	6.4	Bladder Normal Adjacent	53.2
(ODO4338)		(ODO4718-03)
Kidney Margin (ODO4338)	10.5	Normal Ovary	18.2
Kidney Ca Nuclear grade ½	5.5	Ovarian Cancer 064008	30.1
(ODO4339)
Kidney Margin (ODO4339)	3.8	Ovarian Cancer (ODO4768-07)	2.7
Kidney Ca, Clear cell type	14.1	Ovary Margin (ODO4768-08)	6.6
(ODO4340)
Kidney Margin (ODO4340)	3.1	Normal Stomach	0.8
Kidney Ca, Nuclear grade 3	2.0	Gastric Cancer 9060358	3.9
(ODO4348)
Kidney Margin (ODO4348)	5.0	Stomach Margin 9060359	0.0
Kidney Cancer (ODO4622-01)	1.0	Gastric Cancer 9060395	8.0
Kidney Margin (ODO4622-03)	0.0	Stomach Margin 9060394	1.8
Kidney Cancer (ODO4450-01)	6.5	Gastric Cancer 9060397	12.2
Kidney Margin (ODO4450-03)	11.3	Stomach Margin 9060396	0.0
Kidney Cancer 8120607	2.6	Gastric Cancer 064005	10.7

[1056]

TABLE ANI
Panel 4.1D
		Rel. Exp. (%)	Rel. Exp. (%)
		Ag4413,	Ag4413,
		Run	Run
	Tissue Name	190281896	249495488
	Secondary Th1 act	0.0	0.0
	Secondary Th2 act	0.4	0.0
	Secondary Tr1 act	0.6	0.0
	Secondary Th1 rest	1.1	0.0
	Secondary Th2 rest	0.0	0.0
	Secondary Tr1 rest	0.0	0.0
	Primary Th1 act	0.0	0.0
	Primary Th2 act	0.0	0.0
	Primary Tr1 act	0.0	0.0
	Primary Th1 rest	0.0	0.0
	Primary Th2 rest	0.0	0.0
	Primary Tr1 rest	0.0	0.0
	CD45RA CD4 lymphocyte	0.0	0.0
	act
	CD45RO CD4 lymphocyte	0.0	0.0
	act
	CD8 lymphocyte act	0.0	0.0
	Secondary CD8	0.0	0.0
	lymphocyte rest
	Secondary CD8	0.0	0.0
	lymphocyte act
	CD4 lymphocyte none	0.0	0.0
	2ry Th1/Th2/Tr1_anti-	0.0	0.0
	CD95CH11
	LAK cells rest	0.0	0.0
	LAK cells IL-2	0.0	0.0
	LAK cells	0.0	0.0
	IL-2 + IL-12
	LAK cells IL-2 + IFN	0.0	0.0
	gamma
	LAK cells	0.0	0.0
	IL-2 + IL-18
	LAK cells PMA/ionomycin	0.0	0.0
	NK Cells IL-2 rest	0.0	0.0
	Two Way MLR 3 day	0.0	0.0
	Two Way MLR 5 day	2.2	0.0
	Two Way MLR 7 day	0.0	0.0
	PBMC rest	0.0	0.0
	PBMC PWM	0.0	0.0
	PBMC PHA-L	0.0	0.0
	Ramos (B cell) none	0.0	0.0
	Ramos (B cell)	0.0	0.0
	ionomycin
	B lymphocytes PWM	0.0	0.0
	B lymphocytes CD40L and	0.0	0.0
	IL-4
	EOL-1 dbcAMP	0.0	0.0
	EOL-1 dbcAMP	0.0	0.0
	PMA/ionomycin
	Dendritic cells none	0.0	0.0
	Dendritic cells LPS	5.8	0.0
	Dendritic cells	0.0	0.0
	anti-CD40
	Monocytes rest	0.0	0.0
	Monocytes LPS	0.0	0.0
	Macrophages rest	0.0	0.0
	Macrophages LPS	0.0	0.0
	HUVEC none	33.4	14.9
	HUVEC starved	55.9	20.6
	HUVEC IL-1beta	16.6	12.1
	HUVEC IFN gamma	52.9	53.2
	HUVEC TNF alpha + IFN	5.0	0.0
	gamma
	HUVEC TNF alpha + IL4	6.4	0.0
	HUVEC IL-11	49.3	54.0
	Lung Microvascular EC	33.0	25.0
	none
	Lung Microvascular EC	42.9	8.7
	TNFalpha + IL-1beta
	Microvascular Dermal EC	15.7	0.4
	none
	Microsvasular Dermal EC	5.5	3.0
	TNFalpha + IL-1beta
	Bronchial epithelium	0.0	0.0
	TNFalpha + IL1beta
	Small airway epithelium	0.0	0.0
	none
	Small airway epithelium	0.0	0.0
	TNFalpha + IL-1beta
	Coronery artery	3.6	2.8
	SMC rest
	Coronery artery SMC	1.9	2.8
	TNFalpha + IL-1beta
	Astrocytes rest	0.0	0.9
	Astrocytes	0.0	0.0
	TNFalpha + IL-1beta
	KU-812 (Basophil) rest	5.8	0.0
	KU-812 (Basophil)	0.9	0.0
	PMA/ionomycin
	CCD1106 (Keratinocytes)	0.0	0.0
	none
	CCD1106 (Keratinocytes)	0.0	0.0
	TNFalpha + IL-1beta
	Liver cirrhosis	0.4	0.0
	NCI-H292 none	0.0	0.0
	NCI-H292 IL-4	0.0	0.0
	NCI-H292 IL-9	0.0	0.0
	NCI-H292 IL-13	0.0	0.0
	NCI-H292 IFN gamma	0.0	0.0
	HPAEC none	71.2	25.7
	HPAEC TNF	100.0	100.0
	alpha + IL-1beta
	Lung fibroblast none	0.0	0.0
	Lung fibroblast	0.3	0.0
	TNF alpha + IL-1 beta
	Lung fibroblast IL-4	0.3	0.0
	Lung fibroblast IL-9	0.0	0.0
	Lung fibroblast IL-13	0.0	0.0
	Lung fibroblast IFN	0.0	0.0
	gamma
	Dermal fibroblast	0.0	0.0
	CCD1070 rest
	Dermal fibroblast	0.0	0.0
	CCD1070 TNF alpha
	Dermal fibroblast	0.0	0.0
	CCD1070 EL-1 beta
	Dermal fibroblast IFN	0.0	0.0
	gamma
	Dermal fibroblast IL-4	0.0	0.0
	Dermal Fibroblasts rest	0.4	0.0
	Neutrophils	0.0	0.0
	TNFa + LPS
	Neutrophils rest	0.0	0.0
	Colon	0.0	0.0
	Lung	5.7	0.0
	Thymus	2.7	0.3
	Kidney	0.0	0.8

[1057]

TABLE ANJ
Panel 4D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag2430, Run		Ag2430, Run
Tissue Name	159506306	Tissue Name	159506306
Secondary Th1 act	0.0	HUVEC IL-1beta	5.9
Secondary Th2 act	0.6	HUVEC IFN gamma	40.3
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN gamma	5.1
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	4.0
Secondary Th2 rest	0.0	HUVEC IL-11	47.3
Secondary Tr1 rest	0.0	Lung Microvascular EC none	22.1
Primary Th1 act	0.0	Lung Microvascular EC TNFalpha +	22.5
		IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC none	20.4
Primary Tr1 act	0.0	Microsvasular Dermal EC	3.8
		TNFalpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium TNFalpha +	0.0
		IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	0.0
Primary Tr1 rest	0.0	Small airway epithelium TNFalpha +	0.0
		IL-1beta
CD45RA CD4 lymphocyte act	0.0	Coronery artery SMC rest	4.2
CD45RO CD4 lymphocyte act	0.0	Coronery artery SMC TNFalpha +	2.1
		IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	1.1
Secondary CD8 lymphocyte rest	0.0	Astrocytes TNFalpha + IL-1beta	0.9
Secondary CD8 lymphocyte act	0.0	KU-812 (Basophil) rest	0.0
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	0.0	CCD1106 (Keratinocytes) none	0.0
CH11
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNFalpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.4
LAK cells IL-2 + IL-12	0.0	Lupus kidney	0.2
LAK cells IL-2 + IFN gamma	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-4	0.0
LAK cells PMA/ionomycin	0.0	NCI-H292 IL-9	0.0
NK Cells IL-2 rest	0.0	NCI-H292 IL-13	0.0
Two Way MLR 3 day	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 5 day	0.0	HPAEC none	85.3
Two Way MLR 7 day	0.0	HPAEC TNF alpha + IL-1 beta	56.6
PBMC rest	0.0	Lung fibroblast none	0.0
PBMC PWM	0.0	Lung fibroblast TNF alpha + IL-1	0.0
		beta
PBMC PHA-L	0.0	Lung fibroblast IL-4	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) ionomycin	0.0	Lung fibroblast IL-13	0.0
B lymphocytes PWM	0.0	Lung fibroblast IFN gamma	0.0
B lymphocytes CD40L and IL-4	0.0	Dermal fibroblast CCD1070 rest	0.0
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070 TNF	0.0
		alpha
EOL-1 dbcAMP PMA/ionomycin	0.0	Dermal fibroblast CCD1070 IL-1	0.0
		beta
Dendritic cells none	0.0	Dermal fibroblast IFN gamma	0.0
Dendritic cells LPS	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells anti-CD40	0.0	IBD Colitis 2	0.0
Monocytes rest	0.0	IBD Crohn's	0.0
Monocytes LPS	0.0	Colon	0.7
Macrophages rest	0.0	Lung	3.1
Macrophages LPS	0.0	Thymus	2.6
HUVEC none	38.7	Kidney	7.2
HUVEC starved	100.0

[1058]

TABLE ANK
Panel CNS_1
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag2430, Run		Ag2430, Run
Tissue Name	171656292	Tissue Name	171656292
BA4 Control	0.0	BA17 PSP	2.9
BA4 Control2	19.6	BA17 PSP2	0.0
BA4 Alzheimer's2	0.0	Sub Nigra Control	94.0
BA4 Parkinson's	0.0	Sub Nigra Control2	25.9
BA4 Parkinson's2	17.0	Sub Nigra Alzheimer's2	15.7
BA4 Huntington's	9.8	Sub Nigra Parkinson's2	36.6
BA4 Huntington's2	0.0	Sub Nigra Huntington's	100.0
BA4 PSP	0.0	Sub Nigra Huntington's2	2.8
BA4 PSP2	11.0	Sub Nigra PSP2	29.1
BA4 Depression	19.5	Sub Nigra Depression	62.4
BA4 Depression2	0.0	Sub Nigra Depression2	0.0
BA7 Control	40.1	Glob Palladus Control	51.4
BA7 Control2	26.1	Glob Palladus Control2	5.1
BA7 Alzheimer's2	0.0	Glob Palladus Alzheimer's	21.3
BA7 Parkinson's	0.0	Glob Palladus Alzheimer's2	0.0
BA7 Parkinson's2	16.6	Glob Palladus Parkinson's	0.0
BA7 Huntington's	15.2	Glob Palladus Parkinson's2	31.4
BA7 Huntington's2	0.0	Glob Palladus PSP	0.0
BA7 PSP	0.0	Glob Palladus PSP2	4.5
BA7 PSP2	14.7	Glob Palladus Depression	44.4
BA7 Depression	4.3	Temp Pole Control	4.3
BA9 Control	7.1	Temp Pole Control2	9.5
BA9 Control2	30.8	Temp Pole Alzheimer's	3.6
BA9 Alzheimer's	0.0	Temp Pole Alzheimer's2	0.0
BA9 Alzheimer's2	0.0	Temp Pole Parkinson's	3.0
BA9 Parkinson's	0.0	Temp Pole Parkinson's2	19.8
BA9 Parkinson's2	33.9	Temp Pole Huntington's	10.7
BA9 Huntington's	37.4	Temp Pole PSP	0.0
BA9 Huntington's2	0.0	Temp Pole PSP2	1.7
BA9 PSP	0.0	Temp Pole Depression2	2.5
BA9 PSP2	1.9	Cing Gyr Control	86.5
BA9 Depression	5.2	Cing Gyr Control2	26.6
BA9 Depression2	0.0	Cing Gyr Alzheimer's	15.3
BA17 Control	28.3	Cing Gyr Alzheimer's2	13.0
BA17 Control2	20.6	Cing Gyr Parkinson's	0.0
BA17 Alzheimer's2	7.0	Cing Gyr Parkinson's2	49.3
BA17 Parkinson's	0.0	Cing Gyr Huntington's	58.6
BA17 Parkinson's2	27.2	Cing Gyr Huntington's2	0.0
BA17 Huntington's	23.7	Cing Gyr PSP	0.0
BA17 Huntington's2	0.0	Cing Gyr PSP2	17.0
BA17 Depression	24.5	Cing Gyr Depression	49.3
BA17 Depression2	27.9	Cing Gyr Depression2	19.1

[1059] AI_comprehensive panel_v1.0 Summary: Ag4413 Highest expression of this gene is seen in a sample from a patient with Crohn's disease (CT=29.4). Moderate levels of expression are also seen in a cluster of tissues derived from patients with asthma and OA. This gene encodes a protein with homology to members of the ADAMTS family. ADAMTS proteins have been implicated in extracellular proteolysis and may play a critical role in the tissue degradation seen in arthritis and other inflammatory conditions. (Martel-Pelletier J. (2001) Best Pract Res Clin Rheumatol 15(5):805-29) Therefore, therapeutic modulation of the expression or function of this gene through the use of human monoclonal antibodies or small molecule drugs may be effective in the treatment of osteoarthritis and other autoimmune diseases.

[1060] CNS_neurodegeneration_v1.0 Summary: Ag2430/Ag4413 Two experiments with two different probe and primer sets produce results that are in excellent agreement, with highest expression in the temporal cortex of an Alzheimer's patient (CTs=30-32.7). These results confirm the expression of this gene at low levels in the brain in an independent group of individuals. This gene is found to be upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of the expression or function of this gene may decrease neuronal death and be of use in the treatment of this disease.

[1061] General_screening_panel_v1.4 Summary: Ag4413 Highest expression of this gene is seen in the cerebellum (CT=27). In addition, this gene is expressed at moderate to low levels in all regions of the CNS examined. The high levels of expression in the cerebellum suggest that this gene product may be a useful and specific target for the treatment of CNS disorders that originate in this region, such as autism and the ataxias.

[1062] Among tissues with metabolic function, this gene is expressed at moderate to low levels in adipose, pancreas, heart, and fetal skeletal muscle and liver. This expression suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[1063] In addition, this gene is expressed at much higher levels in fetal kidney tissue (CT=29.6) when compared to expression in the adult counterpart (CT=30.6). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.

[1064] Moderate levels of expression are also seen in cell lines from brain, colon, lung, renal and melanoma cancers. Thus, expression of this gene may potentially be used as a marker of these cancers. Therapeutic modulation of this gene product may also be useful in the treatment of these cancers.

[1065] Oncology_cell_line_screening_panel_v3.2 Summary: Ag2430 Expression of the gene on this panel is limited to cerebellum and lung cancer cell lines. This is in agreement with the expression seen in Panels 1.3D and 1.4. Thus, expression of this gene could be used as a marker of cerebellar tissue and lung cancer and to differentiate these samples from other samples on this panel.

[1066] Panel 1.3D Summary: Ag2430 Expression of the gene in this panel is in agreement with expression in Panel 1.4. Highest expression is seen in the cerebellum (CT=31), with low but significant expression detected in the amygdala, hippocampus, substantia nigra and thalamus. Moderate to low levels of expression are seen in fetal skeletal muscle, adipose, and cancer cell lines derived from melanoma, breast, lung, renal, colon and brain cancers. See Panel 1.4 for further discussion of this gene in human disease.

[1067] Panel 2D Summary: Ag2430 Highest expression of this gene is seen in lung cancer (CT=31). In addition, expression of this gene appears to be upregulated in lung, thyroid, gastric and ovarian cancer when compared to expression in the corresponding normal adjacent tissue. This protein is homologous to members of the family of ADAMTS proteins that are characterized by disintegrin, metalloproteinase and thrombospondin domains. This domain structure alone leads one to speculate that the expression of these genes in the context of cancer might play a role in the progression of the disease, as both metalloproteinases and thrombospondins have been demonstrated to be important to tumor progression. Specifically, the metalloproteinase domain may play a role in cell invasion and metastasis, and the thrombospondin domain may play a role in angiogenesis. (Masui T. Clin Cancer Res Nov. 7, 2001;7(11):3437-4).

[1068] Based on the expression profile of this gene and the role played by ADAMTS proteins in tumor progression, this gene in the correct context might play a role in tumor angiogeneis. Furthermore, therapeutic targeting with antibodies or small molecule drugs directed against this gene product may block the angiogenic and invasion/metastasis promoting activities of this molecule especially in those cancer types where the gene is overexpressed in the tumor compared to the normal adjacent tissue.

[1069] Panel 4.1D Summary: Ag4413 Two experiments with the same probe and primer set produce results that are in excellent agreement. Highest expression is seen in TNF-a and IL-1 beta treated HPAECs. This gene appears to be preferentially expressed in endothelial cells, including microvascular dermal endothelial cells, microvascular lung endothelial cells, human pulmonary aortic endothelial cells and human umbilical vein endothelial cells. Endothelial cells are known to play important roles in inflammatory responses by altering the expression of surface proteins that are involved in activation and recruiting of effector inflammatory cells. The expression of this gene in dermal microvascular endothelial cells suggests that this protein product may be involved in inflammatory responses to skin disorders, including psoriasis. Expression in lung microvascular endothelial cells suggests that the protein encoded by this transcript may also be involved in lung disorders including asthma, allergies, chronic obstructive pulmonary disease, and emphysema. The protein encoded by this gene has homology to ADAMTS family of molecules suggesting that it may function as an enzyme. Based on its homology, it may contribute to the tissue destruction and remodeling processes associated with asthma, ulcerative colitis, emphysema and osteoarthritis. (Kuno K. J Biol Chem Jan. 3, 1997;272(1):556-62;) Therefore, blocking the function of the protein encoded by this gene with human nonoclonal antibody therapeutics or small molecule therapeutics may reduce or inhibit tissue destruction in the lungs, intestine, or joints due to emphysema, allergy, asthma, colitis, or osteoarthritis.

[1070] Panel 4D Summary: Ag2430 Highest expression of the gene in this panel is seen in HUVECs (CT=28). Expression in this panel is in agreement with expression in Panel 4.1D, with preferential expression seen in endothelial cells, including HIPAECs, lung and dermal microvascular ECs, and a cluster of HUVEC samples. See Panel 4D for discussion of this gene in inflammation.

[1071] Panel CNS—1 Summary: Ag2430 This panel confirms the presence of this gene in the brain. See Panels 1.4 and CNS_neurodegeneration for discussion of this gene in the central nervous system.

[1072] AP. CG57635-03: Peroxisomal 3,2-Trans-Enoyl-COA Isomerase

[1073] Expression of gene CG57635-03 was assessed using the primer-probe set Ag1102, described in Table APA. Results of the RTQ-PCR runs are shown in Tables APB and APC.

TABLE APA
Probe Name Ag1102
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-aggatccaggaaacgaagtg-3′	20	842	313
Probe	TET-5′-tctacgcgctatataagcaggccactg-3′-TAMRA	27	805	314
Reverse	5′-gggcatgttacaaggtcctt-3′	20	785	315

[1074]

TABLE APB
Panel 1.2
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag1102,		Ag1102,
	Run		Run
Tissue Name	125939695	Tissue Name	125939695
Endothelial cells	12.3	Renal ca. 786-0	3.4
Heart (Fetal)	6.3	Renal ca. A498	5.4
Pancreas	16.4	Renal ca. RXF 393	3.2
Pancreatic ca. CAPAN 2	0.4	Renal ca. ACHN	4.8
Adrenal Gland	53.6	Renal ca. UO-31	2.2
Thyroid	12.3	Renal ca. TK-10	4.6
Salivary gland	16.3	Liver	29.9
Pituitary gland	13.4	Liver (fetal)	11.9
Brain (fetal)	4.4	Liver ca. (hepatoblast) HepG2	16.6
Brain (whole)	7.9	Lung	4.0
Brain (amygdala)	4.2	Lung (fetal)	1.7
Brain (cerebellum)	7.5	Lung ca. (small cell) LX-1	6.0
Brain (hippocampus)	14.6	Lung ca. (small cell) NCI-H69	2.0
Brain (thalamus)	4.4	Lung ca. (s.cell var.) SHP-77	3.0
Cerebral Cortex	7.0	Lung ca. (large cell)NCI-H460	10.6
Spinal cord	2.7	Lung ca. (non-sm. cell) A549	9.6
glio/astro U87-MG	3.6	Lung ca. (non-s.cell) NCI-H23	4.1
glio/astro U-118-MG	6.4	Lung ca. (non-s.cell) HOP-62	11.6
astrocytoma SW1783	4.0	Lung ca. (non-s.cl) NCI-H522	38.7
neuro*; met SK-N-AS	6.9	Lung ca. (squam.) SW 900	12.2
astrocytoma SF-539	3.7	Lung ca. (squam.) NCI-H596	3.0
astrocytoma SNB-75	1.1	Mammary gland	5.6
glioma SNB-19	3.0	Breast ca.* (pl.ef) MCF-7	3.3
glioma U251	3.0	Breast ca.* (pl.ef) MDA-MB-	6.2
		231
glioma SF-295	4.6	Breast ca.* (pl. ef) T47D	9.6
Heart	32.5	Breast ca. BT-549	12.2
Skeletal Muscle	100.0	Breast ca. MDA-N	1.5
Bone marrow	2.9	Ovary	4.4
Thymus	1.1	Ovarian ca. OVCAR-3	1.4
Spleen	1.3	Ovarian ca. OVCAR-4	15.6
Lymph node	2.0	Ovarian ca. OVCAR-5	4.7
Colorectal Tissue	2.1	Ovarian ca. OVCAR-8	9.5
Stomach	14.5	Ovarian ca. IGROV-1	5.4
Small intestine	6.9	Ovarian ca. (ascites) SK-OV-3	9.4
Colon ca. SW480	1.7	Uterus	6.4
Colon ca.* SW620 (SW480 met)	5.0	Placenta	10.7
Colon ca. HT29	0.3	Prostate	14.5
Colon ca. HCT-116	6.0	Prostate ca.* (bone met) PC-3	57.0
Colon ca. CaCo-2	5.8	Testis	14.1
Colon ca. Tissue (ODO3866)	0.6	Melanoma Hs688(A).T	3.3
Colon ca. HCC-2998	2.7	Melanoma* (met) Hs688(B).T	3.4
Gastric ca.* (liver met) NCI-N87	3.2	Melanoma UACC-62	13.8
Bladder	16.7	Melanoma M14	9.9
Trachea	1.8	Melanoma LOX IMVI	24.8
Kidney	43.2	Melanoma* (met) SK-MEL-5	19.5
Kidney (fetal)	8.1

[1075]

TABLE APC
Panel 5 Islet
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag1102,		Ag1102,
	Run		Run
Tissue Name	296332536	Tissue Name	296332536
97457_Patient-02go_adipose	5.0	94709_Donor 2 AM - A_adipose	13.0
97476_Patient-07sk_skeletal	0.0	94710_Donor 2 AM - B_adipose	8.6
muscle
97477_Patient-07ut_uterus	2.7	94711_Donor 2 AM - C_adipose	7.7
97478_Patient-07pl_placenta	2.4	94712_Donor 2 AD - A_adipose	20.4
99167_Bayer Patient 1	0.0	94713_Donor 2 AD - B_adipose	20.9
97482_Patient-08ut_uterus	2.0	94714_Donor 2 AD - C_adipose	18.7
97483_Patient-08pl_placenta	3.1	94742_Donor 3 U - A_Mesenchymal	4.9
		Stem Cells
97486_Patient-09sk_skeletal	6.2	94743_Donor 3 U - B_Mesenchymal	5.7
muscle		Stem Cells
97487_Patient-09ut_uterus	6.7	94730_Donor 3 AM - A_adipose	25.2
97488_Patient-09pl_placenta	2.3	94731_Donor 3 AM - B_adipose	37.4
97492_Patient-10ut_uterus	4.9	94732_Donor 3 AM - C_adipose	25.7
97493_Patient-10pl_placenta	3.2	94733_Donor 3 AD - A_adipose	32.5
97495_Patient-11go_adipose	5.6	94734_Donor 3 AD - B_adipose	28.9
97496_Patient-11sk_skeletal	12.9	94735_Donor 3 AD - C_adipose	10.1
muscle
97497_Patient-11ut_uterus	7.7	77138_Liver_HepG2untreated	100.0
97498_Patient-11pl_placenta	0.9	73556_Heart_Cardiac stromal cells	12.4
		(primary)
97500_Patient-12go_adipose	9.2	81735_Small Intestine	9.1
97501_Patient-12sk_skeletal	27.2	72409_Kidney_Proximal Convoluted	59.5
muscle		Tubule
97502_Patient-12ut_uterus	7.2	82685_Small intestine_Duodenum	7.5
97503_Patient-12pl_placenta	3.3	90650_Adrenal_Adrenocortical	11.4
		adenoma
94721_Donor 2 U -	16.0	72410_Kidney_HRCE	20.7
A_Mesenchymal Stem Cells
94722_Donor 2 U -	11.6	72411_Kidney_HRE	10.7
B_Mesenchymal Stem Cells
94723_Donor 2 U -	13.5	73139_Uterus_Uterine smooth muscle	33.4
C_Mesenchymal Stem Cells		cells

[1076] Panel 1.2 Summary: Ag1102 Highest expression of the CG57635-03 gene is detected in skeletal muscle (CT=24). High expression of this gene is also seen in tissues with metabolic or endocrine function including pancreas, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[1077] The CG57635-03 gene codes for a variant of peroxisomal 3,2-trans-enoyl-COA isomerase (ECI). Peroxisomes are involved in the beta-oxidation chain shortening of long-chain and very-long-chain fatty acyl-coenzyme (CoAs), long-chain dicarboxylyl-CoAs, the CoA esters of eicosanoids, 2-methyl-branched fatty acyl-CoAs, and the CoA esters of the bile acid intermediates di- and trihydroxycoprostanoic acids. ECI is one of the bi(tri)functional enzyme involved in the beta oxidation pathway (Osmundsen et al., 1991, Biochim Biophys Acta 1085(2):141-58, PMID: 1892883). Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of diseases that affect peroxisomal oxidation such as Zellweger syndrome and adrenoleukodystrophies.

[1078] ECI is a member of the acetyl CoA binding protein (ACBP)/diazepam binding inhibitor (DBI) family. The full-length ACBP is a multifunctional 10 Kda protein that is ubiquitously expressed and highly conserved across many species. ACBP is also processed into a number of biologically active peptides. These polypeptides have diverse functions and act on the central nervous system, the gastrointestinal tract and endocrine systems. Interestingly, peptides derived from ACBP can influence steroid secretion from the adrenal gland and this may form a physiologic feedback loop (Papadopoulos V and Brown A S, 1995, J Steroid Biochem Mol Biol 53(1-6):103-10). One ACBP-derived peptide (octadecaneuropeptide: ODN—ACBP33-50) exerts its action through several mechanisms. One mechanism influences nutrient absorption through the stimulation of CCK secretion and the subsequent secretion by the exocrine pancreas (Herzig et al., 1996, Proc. Nat. Acad. Sci. 93: 7927-7932). At the same time ODN inhibits glucose-stimulated insulin secretion from the endocrine pancreas (Ostenson et al., 1994, Eur J Endocrinol 131(2):201-4.). Thus, ODN-related peptides derived from ECI encoded by this gene may be useful as potential protein therapeutics for the treatment of metabolic disorders such as obesity and diabetes.

[1079] In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. DBI has been implicated in seizure disorders, drug dependence and memory (Herzog et al., 1996, Neurobiol Learn Mem 66(3):341-52; Ohkuma et al., 2001, Life Sci 68(11):1215-22). Furthermore, this ligand acts at the GABA-A receptor which has been implicated in schizophrenina and bipolar disorder. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia, bipolar disorder and depression.

[1080] High to moderate levels of expression of this gene is also seen in cluster of cancer cell lines derived from gastric, colon, lung, renal, breast, ovarian, prostate, melanoma and brain cancers. Thus, therapeutic modulation of the expression or function of this gene may be effective in the treatment of these cancers.

[1081] Panel 5 Islet Summary: Ag1102 Highest expression of the CG57635-03 gene is detected in untreated liver HepG2 cell line (CT=28). Moderate expression of this gene is also seen adipose, uterus, placenta, skeletal muscle, mesenchymal stem cells, gastrointestinal tract, and kidney. Therapeutic activation of CG57635-03 would be of benefit in cases of genetic deficiency of this fatty acid-oxidizing enzyme and also in Type 2 diabetes or obesity, where it may aid in metabolizing excess dietary fat intake.

[1082] AQ. CG96859-02, CG96859-03 and CG96859-04: Hydroxymethylglutaryl-COA Lyase

[1083] Expression of gene CG96859-02, CG96859-03 and CG96859-04 was assessed using the primer-probe sets Ag4080, Ag4500, Ag4504, Ag4735 and Ag4947, described in Tables AQA, AQB, AQC and AQD. Results of the RTQ-PCR runs are shown in Tables AQE, AQF and AQG. Please note that CG96859-03 and C96859-04 are the full-length clones. Please note that primer-probe set Ag4080 is specific for the CG96859-03 gene and primer-probe sets Ag4500 and Ag4504 are specific for the CG96859-02 gene.

TABLE AQA
Probe Name Ag4080
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gccaaggaagtagtcatctttg-3′	22	646	316
Probe	TET-5′-tgcctcagagctcttcaccaagaaga-3′-TAMRA	26	616	317
Reverse	5′-gcgtcaaacctctgaaaactct-3′	22	573	318

[1084]

TABLE AQB
Probe Name Ag4500
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-atttgtggaaagtggagagcta-3′	22	102	319
Probe	TET-5′-cgtctgccaactccagcatctctg-3′-TAMRA	24	69	320
Reverse	5′-acattcagcgtggagattttc-3′	21	48	321

[1085]

TABLE AQC
Probe Name Ag4504
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggagactcaaggatcatgctaa-3′	22	258	322
Probe	TET-5′-acacgtcctcaggcattcaactcctg-3′-TAMRA	26	298	323
Reverse	5′-ggctgaagtctccctttgttac-3′	22	335	324

[1086]

TABLE AQD
Probe Name Ag4735
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tgaccgctgcctcga-3′	15	990	325
Probe	TET-5′-atgccaggaaacttctgaatgccc-3′-TAMRA	24	1040	326
Reverse	5′-gtgtctcctaagtgggttcc-3′	20	1094	327

[1087]

TABLE AQE
Probe Name Ag4947
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gggtgcccacaccaatg-3′	17	924	328
Probe	TET-5′-tgagtagaacttcttggtgaccgctgc-3′-TAMRA	27	973	329
Reverse	5′-acccagtcctgaccccaaa-3′	19	1016	330

[1088]

TABLE AQF
General_screening_panel_v1.4
		Rel. Exp. (%)	Rel. Exp. (%)
		Ag4504,	Ag4735,
		Run	Run
	Tissue Name	222695221	222262773
	Adipose	0.8	3.1
	Melanoma*	4.6	23.2
	Hs688(A).T
	Melanoma*	3.7	18.7
	Hs688(B).T
	Melanoma*	3.2	19.2
	M14
	Melanoma*	1.1	4.5
	LOXIMVI
	Melanoma* SK-	4.0	13.1
	MEL-5
	Squamous cell	1.3	7.9
	carcinoma SCC-
	4
	Testis Pool	1.4	5.1
	Prostate ca.*	6.3	31.6
	(bone met) PC-3
	Prostate Pool	1.3	3.4
	Placenta	1.3	5.8
	Uterus Pool	0.6	1.2
	Ovarian ca.	2.5	15.0
	OVCAR-3
	Ovarian ca. SK-	4.6	26.2
	OV-3
	Ovarian ca.	2.7	17.2
	OVCAR-4
	Ovarian ca.	6.7	35.1
	OVCAR-5
	Ovarian ca.	2.9	20.0
	IGROV-1
	Ovarian ca.	2.5	15.5
	OVCAR-8
	Ovary	1.6	4.7
	Breast ca. MCF-7	5.0	35.4
	Breast ca.	3.3	20.0
	MDA-MB-231
	Breast ca. BT	9.2	44.4
	549
	Breast ca. T47D	10.9	100.0
	Breast ca.	0.7	2.9
	MDA-N
	Breast Pool	2.0	5.7
	Trachea	1.3	8.6
	Lung	0.7	2.7
	Fetal Lung	2.3	11.8
	Lung ca. NCI-N417	0.5	4.4
	Lung ca. LX-1	4.4	24.0
	Lung ca. NCI-	0.2	2.0
	H146
	Lung ca. SHP-77	1.3	8.7
	Lung ca. A549	2.0	12.9
	Lung ca. NCI-	0.4	4.5
	H526
	Lung ca. NCI-	2.6	18.3
	H23
	Lung ca. NCI-	1.8	11.0
	H460
	Lung ca. HOP-	4.5	15.8
	62
	Lung ca. NCI-	5.3	27.4
	H522
	Liver	3.1	17.0
	Fetal Liver	7.3	26.1
	Liver ca. HepG2	8.0	41.5
	Kidney Pool	2.4	12.5
	Fetal Kidney	2.5	7.7
	Renal ca. 786-0	5.0	29.7
	Renal ca. A498	1.1	5.5
	Renal ca.	2.7	19.1
	ACHN
	Renal ca. UO-31	5.3	7.5
	Renal ca. TK-10	6.3	34.9
	Bladder	2.4	11.4
	Gastric ca. (liver	9.5	51.4
	met.) NCI-N87
	Gastric ca. KATO	8.5	42.6
	III
	Colon ca. SW-948	1.4	9.2
	Colon ca. SW480	5.2	19.9
	Colon ca.* (SW480	3.4	20.3
	met) SW620
	Colon ca. HT29	3.6	20.2
	Colon ca. HCT-116	4.4	25.0
	Colon ca. CaCo-2	4.2	18.7
	Colon cancer tissue	1.9	12.0
	Colon ca. SW1116	0.9	8.4
	Colon ca. Colo-205	1.6	10.3
	Colon ca. SW-48	1.3	6.5
	Colon Pool	2.1	6.2
	Small Intestine	1.3	4.7
	Pool
	Stomach Pool	1.0	3.6
	Bone Marrow Pool	1.0	2.1
	Fetal Heart	1.0	4.0
	Heart Pool	1.3	6.2
	Lymph Node Pool	1.8	6.1
	Fetal Skeletal	1.2	4.5
	Muscle
	Skeletal Muscle	2.7	19.9
	Pool
	Spleen Pool	1.0	5.1
	Thymus Pool	1.2	5.2
	CNS cancer	6.1	42.3
	(glio/astro) U87-
	MG
	CNS cancer	5.2	25.5
	(glio/astro) U-118-
	MG
	CNS cancer	1.8	10.9
	(neuro; met) SK-N-
	AS
	CNS cancer (astro)	3.3	23.8
	SF-539
	CNS cancer (astro)	8.8	63.3
	SNB-75
	CNS cancer (glio)	2.6	23.2
	SNB-19
	CNS cancer (glio)	8.6	41.5
	SF-295
	Brain (Amygdala)	0.7	7.0
	Pool
	Brain (cerebellum)	100.0	8.5
	Brain (fetal)	0.9	5.0
	Brain	1.2	9.5
	(Hippocampus)
	Pool
	Cerebral Cortex	1.3	7.3
	Pool
	Brain (Substantia	1.2	10.0
	nigra) Pool
	Brain (Thalamus)	1.3	12.1
	Pool
	Brain (whole)	1.3	7.5
	Spinal Cord Pool	1.6	15.8
	Adrenal Gland	4.0	12.3
	Pituitary gland Pool	0.6	2.5
	Salivary Gland	1.1	5.1
	Thyroid (female)	1.9	10.2
	Pancreatic ca.	4.4	30.4
	CAPAN2
	Pancreas Pool	2.5	8.0

[1089]

TABLE AQG
General_screening_panel_v1.5
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4947, Run		Ag4947, Run
Tissue Name	228714909	Tissue Name	228714909
Adipose	0.6	Renal ca. TK-10	17.2
Melanoma* Hs688(A).T	4.6	Bladder	2.5
Melanoma* Hs688(B).T	3.0	Gastric ca. (liver met.) NCI-N87	13.6
Melanoma* M14	6.9	Gastric ca. KATO III	2.1
Melanoma* LOXIMVI	5.3	Colon ca. SW-948	2.1
Melanoma* SK-MEL-5	4.3	Colon ca. SW480	22.8
Squamous cell carcinoma SCC-4	4.8	Colon ca.* (SW480 met) SW620	15.2
Testis Pool	3.8	Colon ca. HT29	2.9
Prostate ca.* (bone met) PC-3	28.3	Colon ca. HCT-116	28.5
Prostate Pool	2.9	Colon ca. CaCo-2	13.4
Placenta	2.3	Colon cancer tissue	5.9
Uterus Pool	1.0	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	10.3	Colon ca. Colo-205	2.8
Ovarian ca. SK-OV-3	16.7	Colon ca. SW-48	2.3
Ovarian ca. OVCAR-4	4.1	Colon Pool	1.2
Ovarian ca. OVCAR-5	28.9	Small Intestine Pool	0.4
Ovarian ca. IGROV-1	8.5	Stomach Pool	1.2
Ovarian ca. OVCAR-8	5.4	Bone Marrow Pool	0.4
Ovary	0.7	Fetal Heart	8.1
Breast ca. MCF-7	7.3	Heart Pool	15.3
Breast ca. MDA-MB-231	7.7	Lymph Node Pool	2.6
Breast ca. BT 549	30.8	Fetal Skeletal Muscle	22.2
Breast ca. T47D	0.3	Skeletal Muscle Pool	100.0
Breast ca. MDA-N	4.3	Spleen Pool	1.0
Breast Pool	3.2	Thymus Pool	1.9
Trachea	3.6	CNS cancer (glio/astro) U87-MG	33.0
Lung	0.6	CNS cancer (glio/astro) U-118-	24.5
		MG
Fetal Lung	5.9	CNS cancer (neuro;met) SK-N-AS	7.2
Lung ca. NCI-N417	5.2	CNS cancer (astro) SF-539	11.7
Lung ca. LX-1	23.7	CNS cancer (astro) SNB-75	20.7
Lung ca. NCI-H146	1.7	CNS cancer (glio) SNB-19	6.1
Lung ca. SHP-77	11.1	CNS cancer (glio) SF-295	20.9
Lung ca. A549	16.7	Brain (Amygdala) Pool	27.5
Lung ca. NCI-H526	4.2	Brain (cerebellum)	59.0
Lung ca. NCI-H23	6.6	Brain (fetal)	16.6
Lung ca. NCI-H460	5.4	Brain (Hippocampus) Pool	20.2
Lung ca. HOP-62	15.4	Cerebral Cortex Pool	38.4
Lung ca. NCI-H522	73.2	Brain (Substantia nigra) Pool	30.8
Liver	3.7	Brain (Thalamus) Pool	33.2
Fetal Liver	11.1	Brain (whole)	7.9
Liver ca. HepG2	28.5	Spinal Cord Pool	39.5
Kidney Pool	3.1	Adrenal Gland	3.3
Fetal Kidney	1.4	Pituitary gland Pool	0.3
Renal ca. 786-0	16.0	Salivary Gland	1.7
Renal ca. A498	1.6	Thyroid (female)	2.3
Renal ca. ACHN	18.2	Pancreatic ca. CAPAN2	8.6
Renal ca. UO-31	16.4	Pancreas Pool	0.8

[1090]

TABLE AQH
Panel 5D
	Rel. Exp. (%)	Rel. Exp. (%)	Rel. Exp. (%)	Rel. Exp. (%)
	Ag4500, Run	Ag4504, Run	Ag4735, Run	Ag4947, Run
Tissue Name	197091043	200923137	204263058	220260116
97457_Patient-02go_adipose	22.4	18.8	12.0	2.0
97476_Patient-07sk_skeletal	9.7	11.6	9.8	8.7
muscle
97477_Patient-07ut_uterus	5.8	10.2	12.4	0.8
97478_Patient-07pl_placenta	8.1	8.4	17.8	1.8
97481_Patient-08sk_skeletal	17.4	5.5	5.6	4.3
muscle
97482_Patient-08ut_uterus	4.0	3.4	11.6	0.0
97483_Patient-08pl_placenta	7.0	9.8	8.8	2.1
97486_Patient-09sk_skeletal	5.7	5.5	5.4	9.9
muscle
97487_Patient-09ut_uterus	7.2	14.1	10.8	2.3
97488_Patient-09pl_placenta	6.3	11.0	10.8	0.0
97492_Patient-10ut_uterus	12.5	9.0	7.3	1.8
97493_Patient-10pl_placenta	10.4	19.2	40.9	6.6
97495_Patient-11go_adipose	4.4	15.9	11.9	0.0
97496_Patient-11sk_skeletal	14.2	24.0	41.2	66.4
muscle
97497_Patient-11ut_uterus	9.8	16.3	20.2	1.0
97498_Patient-11pl_placenta	4.5	10.1	17.6	2.6
97500_Patient-12go_adipose	9.6	12.0	15.6	2.5
97501_Patient-12sk_skeletal	19.1	32.1	88.9	100.0
muscle
97502_Patient-12ut_uterus	17.4	34.9	19.6	0.6
97503_Patient-12pl_placenta	6.3	9.2	18.2	4.4
94721_Donor 2 U -	6.7	15.7	22.7	2.8
A_Mesenchymal Stem Cells
94722_Donor 2 U -	6.0	9.5	18.4	3.2
B_Mesenchymal Stem Cells
94723_Donor 2 U -	5.8	11.0	16.4	0.6
C_Mesenchymal Stem Cells
94709_Donor 2 AM - A_adipose	5.9	9.9	37.1	1.6
94710_Donor 2 AM - B_adipose	8.8	21.2	14.9	0.6
94711_Donor 2 AM - C_adipose	5.6	13.2	12.0	2.3
94712_Donor 2 AD - A_adipose	10.4	22.4	36.1	7.4
94713_Donor 2 AD - B_adipose	15.8	33.2	40.3	4.4
94714_Donor 2 AD - C_adipose	17.6	28.3	24.8	1.5
94742_Donor 3 U -	4.1	10.1	18.8	11.0
A_Mesenchymal Stem Cells
94743_Donor 3 U -	9.5	17.8	18.7	2.3
B_Mesenchymal Stem Cells
94730_Donor 3 AM - A_adipose	10.2	19.3	16.0	4.8
94731_Donor 3 AM - B_adipose	8.2	12.5	16.2	0.0
94732_Donor 3 AM - C_adipose	4.8	15.1	11.4	4.2
94733_Donor 3 AD - A_adipose	11.5	21.8	46.0	3.2
94734_Donor 3 AD - B_adipose	5.9	10.7	19.9	0.9
94735_Donor 3 AD - C_adipose	15.0	22.5	19.5	0.0
77138_Liver_HepG2untreated	100.0	100.0	100.0	35.4
73556_Heart_Cardiac stromal cells	9.5	9.9	4.3	2.1
(primary)
81735_Small Intestine	9.5	23.0	23.5	0.7
72409_Kidney_Proximal	11.9	11.2	11.8	3.2
Convoluted Tubule
82685_Small intestine_Duodenum	8.2	18.0	27.4	4.8
90650_Adrenal_Adrenocortical	10.4	20.3	8.2	0.0
adenoma
72410_Kidney_HRCE	47.3	42.6	57.4	22.2
72411_Kidney_HRE	21.9	23.8	25.2	8.5
73139_Uterus_Uterine smooth	10.8	12.4	12.5	4.3
muscle cells

[1091] General_screening_panel_v1.4 Summary: Ag4735 Highest expression of this gene is seen in a breast cancer T47D cell line (CT=26). High to moderate levels of expression of this gene is also detected in in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, therapeutic modulation of the expression or function of this gene may be effective in the treatment of these cancers.

[1092] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[1093] This gene codes for a variant of hydroxymethylglutaryl-COA lyase (HMG-CoA lyase). Deficiency in HMG-CoA lyase protein results in an inborn error of leucine catabolism which often leads to life-threatening illness in the neonatal period. The cardinal clinical features include severe infantile hypoglycemia, metabolic acidosis, hepatomegaly, lethargy or coma and apnea (Gibson et al., 1988, Eur J Pediatr 148(3):180-6, PMID: 3063529). Therefore, therapeutic modulation of the expression of this gene or protein encoded by this gene may be useful in the treatment infantile hypoglycemia, metabolic acidosis, hepatomegaly, lethargy or coma and apnea.

[1094] In addition, this gene is expressed at moderate levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[1095] Another experiment with probe Ag4504 shows similar ubiquitous expression pattern for this gene with highest expression in cerebellum (CT=22.8).

[1096] Ag4080 Expression of the CG96859-03 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[1097] General_screening_panel_v1.5 Summary: Ag4947 Highest expression of this gene is seen in skeletal muscle (CT=30.4). Therefore, expression of this gene may be used to differentiate skeletal muscle from other samples used in this panel. In addition, therapeutic modulation of this gene may be useful in the treatment of muscle related disorders.

[1098] Moderate to low levels of expression of this gene is also seen in in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord and in number of cancer cell lines derived from pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. See panel 1.4 for further discussion of this gene.

[1099] Panel 5D Summary: Ag4500/Ag4504/Ag4735 Three experiments with three different probe and primer sets are in very good agreement with highest expression of this gene in untreated liver HepG2 samples (CTs=28-30). Moderate to low expression of this gene is seen in most of the samples used in this panel including skeletal muscle, uterus, placenta, mesenchymal stem cells, adrenocortical adenoma, small intestine and kidney. This gene is also well-expressed in subcutaneous adipose tissue. HMG-CoA lyase is a key mitochondrial enzyme involved in the biogenesis of free fatty acids and ketone bodies. Inhibition of this key enzyme may decrease the amount of lipid synthesized by adipose tissue and be a treatment for obesity and Type 2 diabetes. In another experiment with probe Ag4947 high expression of this gene is seen mainly in skeletal muscle (CT=32.5). Low but significant levels of expression was also seen in untreated liver HepG2 samples and kidney. See panel 1.4 for further discussion of this gene.

[1100] Ag4080 Expression of the CG96859-03 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[1101] AR. CG96859-05: Hydroxymethylglutaryl-COA Lyase, Mitochondrial Precursor

[1102] Expression of gene CG96859-05 was assessed using the primer-probe sets Ag4080 and Ag4948, described in Tables ARA and ARB. Results of the RTQ-PCR runs are shown in Tables ARC and ARD.

TABLE ARA
Probe Name Ag4080
			Start
Primers	Sequences	Length Position	SEQ ID No
Forward	5′-gccaaggaagtagtcatctttg-3′	22	511	331
Probe	TET-5′-tgcctcagagctcttcaccaagaaga-3′-	26	481	332
	TAMRA
Reverse	5′-gcgtcaaacctctgaaaactct-3′	22	438	333

[1103]

TABLE ARB
Probe Name Ag4948
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-atgaagggaagatctcccca-3′	20	347	334
Probe	TET-5′-ctgaggaagtgcctctggctgccct-3′-	25	312	335
	TAMRA
Reverse	5′-ataggtgtcatggcagtgg-3′	19	287	336

[1104]

TABLE ARC
General_screening_panel_v1.5
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4948, Run		Ag4948, Run
Tissue Name	228720111	Tissue Name	228720111
Adipose	0.9	Renal ca. TK-10	54.3
Melanoma* Hs688(A).T	44.1	Bladder	15.4
Melanoma* Hs688(B).T	33.4	Gastric ca. (liver met.) NCI-N87	67.4
Melanoma* M14	25.2	Gastric ca. KATO III	80.1
Melanoma* LOXIMVI	6.8	Colon ca. SW-948	13.4
Melanoma* SK-MEL-5	23.8	Colon ca. SW480	42.9
Squamous cell carcinoma	5.9	Colon ca.* (SW480 met) SW620	25.9
SCC-4
Testis Pool	4.1	Colon ca. HT29	26.1
Prostate ca.* (bone met)	39.5	Colon ca. HCT-116	38.4
PC-3
Prostate Pool	5.2	Colon ca. CaCo-2	21.2
Placenta	12.0	Colon cancer tissue	19.8
Uterus Pool	0.0	Colon ca. SW1116	6.3
Ovarian ca. OVCAR-3	23.5	Colon ca. Colo-205	14.7
Ovarian ca. SK-OV-3	48.6	Colon ca. SW-48	14.9
Ovarian ca. OVCAR-4	21.5	Colon Pool	7.9
Ovarian ca. OVCAR-5	56.3	Small Intestine Pool	4.4
Ovarian ca. IGROV-1	24.0	Stomach Pool	4.0
Ovarian ca. OVCAR-8	27.2	Bone Marrow Pool	1.3
Ovary	11.3	Fetal Heart	0.4
Breast ca. MCF-7	46.7	Heart Pool	1.8
Breast ca. MDA-MB-231	36.6	Lymph Node Pool	7.8
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	3.5
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.1
Breast ca. MDA-N	5.0	Spleen Pool	6.0
Breast Pool	4.9	Thymus Pool	7.4
Trachea	10.1	CNS cancer (glio/astro) U87-MG	32.8
Lung	1.8	CNS cancer (glio/astro) U-118-	44.8
		MG
Fetal Lung	13.5	CNS cancer (neuro;met) SK-N-AS	12.9
Lung ca. NCI-N417	2.5	CNS cancer (astro) SF-539	27.4
Lung ca. LX-1	29.7	CNS cancer (astro) SNB-75	100.0
Lung ca. NCI-H146	0.5	CNS cancer (glio) SNB-19	24.0
Lung ca. SHP-77	9.7	CNS cancer (glio) SF-295	56.3
Lung ca. A549	21.0	Brain (Amygdala) Pool	1.8
Lung ca. NCI-H526	2.6	Brain (cerebellum)	0.0
Lung ca. NCI-H23	27.4	Brain (fetal)	2.4
Lung ca. NCI-H460	17.1	Brain (Hippocampus) Pool	3.0
Lung ca. HOP-62	24.1	Cerebral Cortex Pool	4.2
Lung ca. NCI-H522	31.9	Brain (Substantia nigra) Pool	0.0
Liver	23.7	Brain (Thalamus) Pool	1.3
Fetal Liver	61.6	Brain (whole)	0.4
Liver ca. HepG2	54.3	Spinal Cord Pool	6.1
Kidney Pool	12.3	Adrenal Gland	16.4
Fetal Kidney	11.1	Pituitary gland Pool	3.3
Renal ca. 786-0	39.8	Salivary Gland	10.0
Renal ca. A498	5.6	Thyroid (female)	15.2
Renal ca. ACHN	18.8	Pancreatic ca. CAPAN2	34.9
Renal ca. UO-31	51.4	Pancreas Pool	15.2

[1105]

TABLE ARD
Panel 5D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4948,		Ag4948,
	Run		Run
Tissue Name	220260117	Tissue Name	220260117
97457_Patient-	13.6	94709_Donor 2 AM - A_adipose	22.1
02go_adipose
97476_Patient-07sk_skeletal	3.2	94710_Donor 2 AM - B_adipose	0.0
muscle
97477_Patient-07ut_uterus	16.6	94711_Donor 2 AM - C_adipose	7.7
97478_Patient-	7.0	94712_Donor 2 AD - A_adipose	12.5
07pl_placenta
97481_Patient-08sk_skeletal	9.0	94713_Donor 2 AD - B_adipose	28.7
muscle
97482_Patient-08ut_uterus	6.2	94714_Donor 2 AD - C_adipose	0.0
97483_Patient-	0.0	94742_Donor 3 U - A_Mesenchymal Stem	10.6
88pl_placenta		Cells
97486_Patient-09sk_skeletal	4.0	94743_Donor 3 U - B_Mesenchymal Stem	22.8
muscle		Cells
97487_Patient-09ut_uterus	13.1	94730_Donor 3 AM - A_adipose	1.7
97488_Patient-	1.2	94731_Donor 3 AM - B_adipose	0.6
09pl_placenta
97492_Patient-10ut_uterus	7.1	94732_Donor 3 AM - C_adipose	0.0
97493_Patient-	10.2	94733_Donor 3 AD - A_adipose	0.0
10pl_placenta
97495_Patient-	11.5	94734_Donor 3 AD - B_adipose	11.6
11go_adipose
97496_Patient-11sk_skeletal	14.7	94735_Donor 3 AD - C_adipose	12.4
muscle
97497_Patient-11ut_uterus	25.9	77138_Liver_HepG2untreated	100.0
97498_Patient-	0.9	73556_Heart_Cardiac stromal cells (primary)	1.8
11pl_placenta
97500_Patient-	16.2	81735_Small Intestine	18.8
12go_adipose
97501_Patient-12sk_skeletal	56.3	72409_Kidney_Proximal Convoluted Tubule	0.0
muscle
97502_Patient-12ut_uterus	23.0	82685_Small intestine_Duodenum	21.9
97503_Patient-	1.6	90650_Adrenal_Adrenocortical adenoma	20.6
12pl_placenta
94721_Donor 2 U -	11.4	72410_Kidney_HRCE	51.8
A_Mesenchymal Stem Cells
94722_Donor 2 U -	6.5	72411_Kidney_HRE	15.7
B_Mesenchymal Stem Cells
94723_Donor 2 U -	17.6	73139_Uterus_Uterine smooth muscle cells	3.6
C_Mesenchymal Stem Cells

[1106] General_screening_panel_v1.4 Summary: Ag4080 Expression of the CG96859-03 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[1107] General_screening_panel_v1.5 Summary: Ag4948 Highest expression of this gene is detected in brain cancer SNB-75 cell lines (CT=29.5). Moderate levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene may be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[1108] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to low levels in pancreas, adrenal gland, thyroid, pituitary gland, fetal skeletal muscle, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[1109] This gene codes for a variant of hydroxymethylglutaryl-COA lyase (HMG-CoA lyase). Deficiency in HMG-CoA lyase protein results in an inborn error of leucine catabolism which often leads to life-threatening illness in the neonatal period. The cardinal clinical features include severe infantile hypoglycemia, metabolic acidosis, hepatomegaly, lethargy or coma and apnea (Gibson et al., 1988, Eur J Pediatr 148(3):180-6, PMID: 3063529). Therefore, therapeutic modulation of the expression of this gene or protein encoded by this gene may be useful in the treatment infantile hypoglycemia, metabolic acidosis, hepatomegaly, lethargy or coma and apnea.

[1110] Interestingly, this gene is expressed at much higher levels in fetal (CT=34.3) when compared to adult skeletal muscle (CT=38.9). This observation suggests that expression of this gene can be used to distinguish fetal from adult skeletal muscle. In addition, the relative overexpression of this gene in fetal skeletal muscle suggests that the protein product may enhance muscular growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the GPCR encoded by this gene could be useful in treatment of muscle related diseases. More specifically, treatment of weak or dystrophic muscle with the protein encoded by this gene could restore muscle mass or function.

[1111] In addition, this gene is expressed at low levels in fetal brain and in some of the regions of the adult brain examined, including hippocampus, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[1112] Panel 5D Summary: Ag4948 Highest expression of the CG96859-05 gene is detected in untreated liver HepG2 samples (CTs=28-30). Low levels of expression of this gene is seen in adipose, skeletal muscle, uterus, mesenchymal stem cells, adrenal adrenocortical adenoma, small intestine and kidney. In another experiment with probe and primer set for Ag4947 shows high expression of this gene mainly in skeletal muscle (CT=32.5). Low but significant levels of expression was also seen in untreated liver HepG2 samples and kidney. See panel 1.4 for further discussion of this gene. In another experiment with probe Ag4080 the expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[1113] AS. CG98082-01: Taste Receptor T1R3-like

[1114] Expression of gene CG98082-01 was assessed using the primer-probe set Ag4142, described in Table ASA. Results of the RTQ-PCR runs are shown in Tables ASB and ASC.

TABLE ASA
Probe Name Ag4142
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-tcctgctgctacgactgtgt-3′	20	1597	337
Probe	TET-5′-ctaccggcaaaacccagacgacat-3′-	24	1595	338
	TAMRA
Reverse	5′-actcatcctggccacaaaa-3′	19	1629	339

[1115]

TABLE ASB
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4142, Run		Ag4142, Run
Tissue Name	220983275	Tissue Name	220983275
Adipose	0.0	Renal ca. TK-10	10.4
Melanoma* Hs688(A).T	0.0	Bladder	0.0
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.) NCI-N87	0.0
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	9.5
Squamous cell carcinoma SCC-	0.0	Colon ca.* (SW480 met) SW620	14.8
4
Testis Pool	0.0	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.0	Colon ca. HCT-116	0.0
Prostate Pool	0.0	Colon ca. CaCo-2	0.0
Placenta	0.0	Colon cancer tissue	0.0
Uterus Pool	0.0	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	7.1	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	9.0	Colon ca. SW-48	59.5
Ovarian ca. OVCAR-4	0.0	Colon Pool	0.0
Ovarian ca. OVCAR-5	5.8	Small Intestine Pool	0.0
Ovarian ca. IGROV-1	0.0	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	0.0	Fetal Heart	1.1
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	0.0
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	43.5	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	9.3
Breast Pool	0.0	Thymus Pool	0.0
Trachea	7.2	CNS cancer (glio/astro) U87-MG	0.0
Lung	0.0	CNS cancer (glio/astro) U-118-	1.8
		MG
Fetal Lung	0.0	CNS cancer (neuro;met) SK-N-AS	0.0
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	57.4	CNS cancer (astro) SNB-75	0.0
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	4.3
Lung ca. SHP-77	36.9	CNS cancer (glio) SF-295	0.0
Lung ca. A549	0.0	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	100.0	Brain (cerebellum)	0.0
Lung ca. NCI-H23	0.0	Brain (fetal)	9.9
Lung ca. NCI-H460	22.5	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	8.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra) Pool	0.0
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	16.6	Spinal Cord Pool	0.0
Kidney Pool	0.0	Adrenal Gland	0.0
Fetal Kidney	0.0	Pituitary gland Pool	7.1
Renal ca. 786-0	0.0	Salivary Gland	26.1
Renal ca. A498	0.0	Thyroid (female)	4.2
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	7.0
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[1116]

TABLE ASC
general oncology screening panel_v_2.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4142,		Ag4142,
	Run		Run
Tissue Name	268392262	Tissue Name	268392262
Colon cancer 1	42.6	Bladder NAT 2	0.0
Colon NAT 1	12.7	Bladder NAT 3	0.0
Colon cancer 2	26.8	Bladder NAT 4	2.4
Colon NAT 2	18.9	Prostate adenocarcinoma 1	6.7
Colon cancer 3	97.9	Prostate adenocarcinoma 2	1.7
Colon NAT 3	19.1	Prostate adenocarcinoma 3	16.8
Colon malignant cancer 4	100.0	Prostate adenocarcinoma 4	17.4
Colon NAT 4	5.3	Prostate NAT 5	8.5
Lung cancer 1	16.4	Prostate adenocarcinoma 6	5.7
Lung NAT 1	1.0	Prostate adenocarcinoma 7	1.9
Lung cancer 2	25.5	Prostate adenocarcinoma 8	0.6
Lung NAT 2	1.3	Prostate adenocarcinoma 9	33.7
Squamous cell carcinoma 3	16.8	Prostate NAT 10	3.3
Lung NAT 3	0.5	Kidney cancer 1	7.5
Metastatic melanoma 1	8.3	Kidney NAT 1	4.8
Melanoma 2	2.0	Kidney cancer 2	29.3
Melanoma 3	2.0	Kidney NAT 2	25.2
Metastatic melanoma 4	25.5	Kidney cancer 3	15.8
Metastatic melanoma 5	27.5	Kidney NAT 3	12.6
Bladder cancer 1	0.3	Kidney cancer 4	12.2
Bladder NAT 1	0.0	Kidney NAT 4	42.0
Bladder cancer 2	3.0

[1117] CNS_neurodegeneration_v1.0 Summary: Ag4142 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[1118] General_screening_panel_v1.4 Summary: Ag4142 Expression of the CG98082-01 gene is highest in a lung cancer cell line (CT=32.8). Expression of this gene is upregulated in a number of lung cancer cell lines when compared to normal lung tissue. Thus, the expression of this gene could be used to distinguish these samples from the other samples in the panel. In addition, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of lung cancer.

[1119] general oncology screening panel_v—2.4 Summary: Ag4142 Expression of the CG98082-01 gene is highest in a malignant colon cancer sample (CT=30.4). Interestingly, expression of this gene appears to be upregulated in colon and lung tumors when compared to the matched normal tissues. In addition, this gene is expressed at significant levels in two malignant melanoma samples. Therefore, expression of the CG98082-01 gene may be used as a marker for colon and lung cancer as well as metastatic melanoma. Furthermore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of lung cancer, colon cancer and metastatic melanoma.

[1120] AT. CG98102-04: Diamine AcetylTransferase-like

[1121] Expression of gene CG98102-04 was assessed using the primer-probe sets Ag4705, Ag4716 and Ag5877, described in Tables ATA, ATB and ATC. Results of the RTQ-PCR runs are shown in Tables ATD, ATE, ATF, ATG and ATH.

TABLE ATA
Probe Name Ag4705
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-ggctaaatatgaatacatggaag-3′	23	67	340
Probe	TET-5′-ttttggagagcaccccttttaccac-3′-	25	130	341
	TAMRA
Reverse	5′-atgctgtgtccttccg-3′	16	192	342

[1122]

TABLE ATB
Probe Name Ag4716
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tgccaaagcctctataatcact-3′	22	287	343
Probe	TET-5′-catcacgaagaagtcctcaagatacaa-3′-	27	260	344
	TAMRA
Reverse	5′-attttacctatgacccgtggat-3′	22	228	345

[1123]

TABLE ATC
Probe Name Ag5877
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-aagaggtgcttctgatctgtcc-3′	22	421	346
Probe	TET-5′-tgaagagggttggagactgttcaagatcg-3′-	29	445	347
	TAMRA
Reverse	5′-catctacagcagcactcctcac-3′	22	508	348

[1124]

TABLE ATD
AI_comprehensive panel_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4716,		Ag4716,
	Run		Run
Tissue Name	244333632	Tissue Name	244333632
110967 COPD-F	12.1	112427 Match Control Psoriasis-F	31.2
110980 COPD-F	2.6	112418 Psoriasis-M	25.9
110968 COPD-M	22.8	112723 Match Control Psoriasis-M	1.4
110977 COPD-M	8.7	112419 Psoriasis-M	37.6
110989 Emphysema-F	36.9	112424 Match Control Psoriasis-M	21.9
110992 Emphysema-F	20.9	112420 Psoriasis-M	60.3
110993 Emphysema-F	16.3	112425 Match Control Psoriasis-M	10.7
110994 Emphysema-F	4.7	104689 (MF) OA Bone-Backus	23.8
110995 Emphysema-F	57.8	104690 (MF) Adj “Normal” Bone-	8.4
		Backus
110996 Emphysema-F	9.4	104691 (MF) OA Synovium-	27.9
		Backus
110997 Asthma-M	6.0	104692 (BA) OA Cartilage-Backus	15.2
111001 Asthma-F	5.4	104694 (BA) OA Bone-Backus	27.7
111002 Asthma-F	19.3	104695 (BA) Adj “Normal” Bone-	20.3
		Backus
111003 Atopic Asthma-F	11.5	104696 (BA) OA Synovium-	34.2
		Backus
111004 Atopic Asthma-F	31.0	104700 (SS) OA Bone-Backus	12.9
111005 Atopic Asthma-F	17.1	104701 (SS) Adj “Normal” Bone-	15.8
		Backus
111006 Atopic Asthma-F	2.2	104702 (SS) OA Synovium-Backus	25.5
111417 Allergy-M	9.3	117093 OA Cartilage Rep7	8.7
112347 Allergy-M	0.7	112672 OA Bone5	64.6
112349 Normal Lung-F	0.3	112673 OA Synovium5	31.4
112357 Normal Lung-F	15.4	112674 OA Synovial Fluid cells5	37.1
112354 Normal Lung-M	9.0	117100 OA Cartilage Rep14	8.1
112374 Crohns-F	16.3	112756 OA Bone9	100.0
112389 Match Control Crohns-F	2.1	112757 OA Synovium9	1.8
112375 Crohns-F	9.7	112758 OA Synovial Fluid Cells9	8.3
112732 Match Control Crohns-F	25.9	117125 RA Cartilage Rep2	5.8
112725 Crohns-M	6.4	113492 Bone2 RA	37.9
112387 Match Control Crohns-M	7.6	113493 Synovium2 RA	15.7
112378 Crohns-M	0.5	113494 Syn Fluid Cells RA	26.1
112390 Match Control Crohns-M	10.6	113499 Cartilage4 RA	58.2
112726 Crohns-M	14.2	113500 Bone4 RA	63.7
112731 Match Control Crohns-M	7.4	113501 Synovium4 RA	57.0
112380 Ulcer Col-F	7.1	113502 Syn Fluid Cells4 RA	33.4
112734 Match Control Ulcer Col-F	71.2	113495 Cartilage3 RA	22.4
112384 Ulcer Col-F	44.1	113496 Bone3 RA	19.6
112737 Match Control Ulcer Col-F	15.5	113497 Synovium3 RA	11.8
112386 Ulcer Col-F	6.6	113498 Syn Fluid Cells3 RA	30.8
112738 Match Control Ulcer Col-F	11.1	117106 Normal Cartilage Rep20	1.1
112381 Ulcer Col-M	0.5	113663 Bone3 Normal	1.2
112735 Match Control Ulcer Col-M	10.2	113664 Synovium3 Normal	0.2
112382 Ulcer Col-M	6.6	113665 Syn Fluid Cells3 Normal	1.1
112394 Match Control Ulcer Col-M	6.6	117107 Normal Cartilage Rep22	3.2
112383 Ulcer Col-M	30.1	113667 Bone4 Normal	27.9
112736 Match Control Ulcer Col-M	2.9	113668 Synovium4 Normal	42.3
112423 Psoriasis-F	11.2	113669 Syn Fluid Cells4 Normal	39.2

[1125]

TABLE ATE
General_screening_panel_v1.4
	Rel. Exp. (%)	Rel. Exp. (%)	Rel. Exp. (%)
	Ag4705,	Ag4716,	Ag4716,
	Run	Run	Run
Tissue Name	213821747	213828317	214237609
Adipose	12.6	8.0	28.5
Melanoma*	2.8	0.9	3.1
Hs688(A).T
Melanoma*	2.0	1.3	4.5
Hs688(B).T
Melanoma*	18.4	9.4	36.9
M14
Melanoma*	1.8	0.4	1.3
LOXIMVI
Melanoma*	14.2	5.8	19.5
SK-MEL-5
Squamous cell	0.8	1.6	5.1
carcinoma
SCC-4
Testis Pool	4.5	1.3	13.8
Prostate ca.*	17.3	4.3	16.4
(bone met) PC-
3
Prostate Pool	2.2	2.1	4.6
Placenta	0.1	9.2	30.6
Uterus Pool	0.3	0.6	2.2
Ovarian ca.	4.7	1.5	6.2
OVCAR-3
Ovarian ca.	9.3	2.2	7.8
SK-OV-3
Ovarian ca.	1.5	0.7	5.7
OVCAR-4
Ovarian ca.	9.2	4.6	31.9
OVCAR-5
Ovarian ca.	40.9	12.9	63.7
1GROV-1
Ovarian ca.	4.1	3.8	25.3
OVCAR-8
Ovary	4.9	2.2	5.8
Breast ca.	2.0	0.8	2.8
MCF-7
Breast ca.	2.9	2.4	6.2
MDA-MB-231
Breast ca. BT	22.2	6.2	21.2
549
Breast ca.	19.2	9.9	47.3
T47D
Breast ca.	40.9	11.0	41.8
MDA-N
Breast Pool	7.5	2.5	7.1
Trachea	38.2	9.0	30.8
Lung	0.9	0.6	3.0
Fetal Lung	65.1	17.6	56.6
Lung ca. NCI-	0.3	0.0	0.3
N417
Lung ca. LX-1	53.6	20.9	100.0
Lung ca. NCI-	0.8	0.1	0.4
H146
Lung ca. SHP-77	1.2	0.5	1.4
Lung ca. A549	23.7	11.1	54.0
Lung ca. NCI-	1.1	0.3	0.8
H526
Lung ca. NCI-	66.9	16.5	84.7
H23
Lung ca. NCI-	1.0	2.4	9.5
H460
Lung ca. HOP-	5.1	2.4	6.3
62
Lung ca. NCI-	3.5	1.8	6.9
H522
Liver	1.4	0.7	3.1
Fetal Liver	14.0	4.8	21.2
Liver ca.	16.7	6.0	27.4
HepG2
Kidney Pool	0.0	3.0	8.7
Fetal Kidney	0.2	1.6	4.8
Renal ca. 786-0	8.1	2.2	7.9
Renal ca. A498	5.8	1.4	5.3
Renal ca.	1.9	0.8	4.0
ACHN
Renal ca. UO-	5.1	6.8	31.0
31
Renal ca. TK-10	11.3	4.2	13.6
Bladder	100.0	20.4	74.7
Gastric ca.	8.1	3.7	15.2
(liver met.)
NCI-N87
Gastric ca.	55.9	15.3	76.8
KATO III
Colon ca. SW-948	2.0	1.6	5.0
Colon ca. SW480	28.7	9.3	28.9
Colon ca.*	38.2	13.1	51.8
(SW480 met)
SW620
Colon ca. HT29	3.8	1.6	4.5
Colon ca.HCT-116	31.0	9.3	28.7
Colon ca. CaCo-2	13.8	4.2	14.0
Colon cancer	45.4	12.4	52.1
tissue
Colon ca. SW1116	1.0	0.3	1.2
Colon ca.	5.6	2.2	9.3
Colo-205
Colon ca. SW-48	3.9	1.1	3.5
Colon Pool	4.8	1.7	4.8
Small Intestine	1.9	1.0	3.3
Pool
Stomach Pool	17.6	4.8	14.3
Bone Marrow Pool	1.4	1.1	3.8
Fetal Heart	2.2	0.6	1.6
Heart Pool	2.0	1.0	2.6
Lymph Node Pool	8.3	2.9	7.4
Fetal Skeletal	0.7	0.3	1.4
Muscle
Skeletal Muscle	0.9	0.5	1.6
Pool
Spleen Pool	8.7	4.7	13.9
Thymus Pool	11.1	4.2	12.9
CNS cancer	12.6	4.7	24.8
(glio/astro)
U87-MG
CNS cancer	18.0	4.5	19.5
(glio/astro)
U-118-MG
CNS cancer	1.0	0.4	2.2
(neuro; met) SK-N-
AS
CNS cancer	0.9	0.4	2.7
(astro) SF-539
CNS cancer	64.6	20.0	57.8
(astro) SNB-75
CNS cancer (glio)	37.9	100.0	62.0
SNB-19
CNS cancer (glio)	66.0	19.2	72.2
SF-295
Brain (Amygdala)	3.5	1.0	2.9
Pool
Brain	1.2	0.4	1.7
(cerebellum)
Brain (fetal)	6.0	1.4	5.1
Brain	5.7	1.8	6.3
(Hippocampus)
Pool
Cerebral Cortex	6.9	1.9	5.8
Pool
Brain (Substantia	7.9	1.7	6.6
nigra) Pool
Brain (Thalamus)	8.6	1.7	6.1
Pool
Brain (whole)	11.2	1.4	4.7
Spinal Cord Pool	7.0	2.1	6.7
Adrenal Gland	14.7	2.7	11.7
Pituitary	4.0	0.8	2.6
gland Pool
Salivary Gland	5.4	1.3	5.0
Thyroid (female)	5.6	5.8	23.8
Pancreatic ca.	9.7	3.2	10.8
CAPAN2
Pancreas Pool	17.0	5.0	13.4

[1126]

TABLE ATF
General_screening_panel_v1.5
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag5877, Run		Ag5877, Run
Tissue Name	248204736	Tissue Name	248204736
Adipose	41.2	Renal ca. TK-10	15.7
Melanoma* Hs688(A).T	3.9	Bladder	100.0
Melanoma* Hs688(B).T	5.5	Gastric ca. (liver met.) NCI-N87	17.1
Melanoma* M14	40.3	Gastric ca. KATO III	58.2
Melanoma* LOXIMVI	1.8	Colon ca. SW-948	6.6
Melanoma* SK-MEL-5	20.6	Colon ca. SW480	30.8
Squamous cell carcinoma SCC-	7.1	Colon ca.* (SW480 met) SW620	62.4
4
Testis Pool	7.5	Colon ca. HT29	4.3
Prostate ca.* (bone met) PC-3	16.4	Colon ca. HCT-116	34.9
Prostate Pool	17.0	Colon ca. CaCo-2	12.4
Placenta	38.2	Colon cancer tissue	59.0
Uterus Pool	7.4	Colon ca. SW1116	1.5
Ovarian ca. OVCAR-3	6.0	Colon ca. Colo-205	6.3
Ovarian ca. SK-OV-3	8.8	Colon ca. SW-48	4.2
Ovarian ca. OVCAR-4	3.2	Colon Pool	8.4
Ovarian ca. OVCAR-5	22.5	Small Intestine Pool	2.4
Ovarian ca. IGROV-1	67.8	Stomach Pool	22.1
Ovarian ca. OVCAR-8	22.1	Bone Marrow Pool	6.4
Ovary	10.7	Fetal Heart	3.4
Breast ca. MCF-7	3.3	Heart Pool	4.5
Breast ca. MDA-MB-231	9.0	Lymph Node Pool	12.7
Breast ca. BT 549	18.3	Fetal Skeletal Muscle	1.5
Breast ca. T47D	14.2	Skeletal Muscle Pool	2.7
Breast ca. MDA-N	33.0	Spleen Pool	20.6
Breast Pool	13.8	Thymus Pool	21.0
Trachea	38.2	CNS cancer (glio/astro) U87-MG	20.9
Lung	4.1	CNS cancer (glio/astro) U-118-	15.5
		MG
Fetal Lung	95.9	CNS cancer (neuro;met) SK-N-AS	1.5
Lung ca. NCI-N417	0.3	CNS cancer (astro) SF-539	0.9
Lung ca. LX-1	84.1	CNS cancer (astro) SNB-75	74.2
Lung ca. NCI-H146	0.5	CNS cancer (glio) SNB-19	80.7
Lung ca. SHP-77	1.9	CNS cancer (glio) SF-295	66.0
Lung ca. A549	43.8	Brain (Amygdala) Pool	4.9
Lung ca. NCI-H526	0.7	Brain (cerebellum)	3.4
Lung ca. NCI-H23	77.9	Brain (fetal)	6.4
Lung ca. NCI-H460	9.9	Brain (Hippocampus) Pool	8.3
Lung ca. HOP-62	5.8	Cerebral Cortex Pool	6.0
Lung ca. NCI-H522	8.6	Brain (Substantia nigra) Pool	5.4
Liver	3.3	Brain (Thalamus) Pool	7.5
Fetal Liver	17.0	Brain (whole)	5.8
Liver ca. HepG2	21.3	Spinal Cord Pool	9.2
Kidney Pool	15.3	Adrenal Gland	15.9
Fetal Kidney	8.5	Pituitary gland Pool	5.6
Renal ca. 786-0	8.1	Salivary Gland	4.3
Renal ca. A498	6.3	Thyroid (female)	28.1
Renal ca. ACHN	2.6	Pancreatic ca. CAPAN2	13.7
Renal ca. UO-31	32.1	Pancreas Pool	22.8

[1127]

TABLE ATG
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4716, Run		Ag4716, Run
Tissue Name	244337062	Tissue Name	244337062
Secondary Th1 act	0.2	HUVEC IL-1beta	16.7
Secondary Th2 act	4.7	HUVEC IFN gamma	13.0
Secondary Tr1 act	1.0	HUVEC TNF alpha + IFN gamma	3.5
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	2.1
Secondary Th2 rest	0.2	HUVEC IL-11	3.6
Secondary Tr1 rest	0.1	Lung Microvascular EC none	4.0
Primary Th1 act	0.0	Lung Microvascular EC	4.9
		TNFalpha + IL-1beta
Primary Th2 act	2.1	Microvascular Dermal EC none	0.3
Primary Tr1 act	1.3	Microvascular Dermal EC	6.3
		TNFalpha + IL-1beta
Primary Th1 rest	0.1	Bronchial epithelium TNFalpha +	53.2
		IL1beta
Primary Th2 rest	0.5	Small airway epithelium none	19.6
Primary Tr1 rest	0.0	Small airway epithelium	53.6
		TNFalpha + IL-1beta
CD45RA CD4 lymphocyte act	4.0	Coronery artery SMC rest	2.8
CD45RO CD4 lymphocyte act	6.3	Coronery artery SMC TNFalpha +	10.0
		IL-1beta
CD8 lymphocyte act	0.3	Astrocytes rest	1.2
Secondary CD8 lymphocyte	2.1	Astrocytes TNFalpha + IL-1beta	2.0
rest
Secondary CD8 lymphocyte act	0.3	KU-812 (Basophil) rest	3.0
CD4 lymphocyte none	0.1	KU-812 (Basophil)	5.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	0.3	CCD1106 (Keratinocytes) none	20.4
CH11
LAK cells rest	5.8	CCD1106 (Keratinocytes)	14.0
		TNFalpha + IL-1beta
LAK cells IL-2	0.8	Liver cirrhosis	6.0
LAK cells IL-2 + IL-12	0.4	NCI-H292 none	73.7
LAK cells IL-2 + IFN gamma	1.3	NCI-H292 IL-4	71.2
LAK cells IL-2 + IL-18	0.4	NCI-H292 IL-9	67.8
LAK cells PMA/ionomycin	58.6	NCI-H292 IL-13	74.2
NK Cells IL-2 rest	3.8	NCI-H292 IFN gamma	20.6
Two Way MLR 3 day	5.3	HPAEC none	1.8
Two Way MLR 5 day	0.7	HPAEC TNF alpha + IL-1 beta	80.7
Two Way MLR 7 day	2.0	Lung fibroblast none	2.9
PBMC rest	1.6	Lung fibroblast TNF alpha + IL-1	17.2
		beta
PBMC PWM	1.0	Lung fibroblast IL-4	1.1
PBMC PHA-L	1.3	Lung fibroblast IL-9	2.1
Ramos (B cell) none	0.2	Lung fibroblast IL-13	0.2
Ramos (B cell) ionomycin	1.5	Lung fibroblast IFN gamma	9.0
B lymphocytes PWM	2.6	Dermal fibroblast CCD1070 rest	1.2
B lymphocytes CD40L and IL-	4.2	Dermal fibroblast CCD1070 TNF	4.6
4		alpha
EOL-1 dbcAMP	6.6	Dermal fibroblast CCD1070 IL-1
		beta
EOL-1 dbcAMP	0.9	Dermal fibroblast IFN gamma	2.9
PMA/ionomycin
Dendritic cells none	6.7	Dermal fibroblast IL-4	1.1
Dendritic cells LPS	7.5	Dermal Fibroblasts rest	1.2
Dendritic cells anti-CD40	0.8	Neutrophils TNFa + LPS	95.3
Monocytes rest	2.0	Neutrophils rest	26.4
Monocytes LPS	100.0	Colon	0.7
Macrophages rest	27.5	Lung	0.9
Macrophages LPS	20.2	Thymus	1.1
HUVEC none	1.4	Kidney	18.3
HUVEC starved	3.1

[1128]

TABLE ATH
Panel 5D
		Rel. Exp. (%)	Rel. Exp. (%)
		Ag4705,	Ag4716,
		Run	Run
	Tissue Name	204245092	204245093
	97457_Patient-	24.1	33.7
	02go_adipose
	97476_Patient-	4.9	12.7
	07sk_skeletal
	muscle
	97477_Patient-	6.6	11.6
	07ut_uterus
	97478_Patient-	69.7	54.3
	07pl_placenta
	97481_Patient-	3.0	4.2
	08sk_skeletal
	muscle
	97482_Patient-	7.4	8.2
	08ut_uterus
	97483_Patient-	26.6	41.2
	08pl_placenta
	97486_Patient-	0.5	1.3
	09sk_skeletal
	muscle
	97487_Patient-	4.3	6.7
	09ut_uterus
	97488_Patient-	47.3	49.3
	09pl_placenta
	97492_Patient-	8.3	12.8
	10ut_uterus
	97493_Patient-	100.0	100.0
	10pl_placenta
	97495_Patient-	6.9	17.7
	11go_adipose
	97496_Patient-	1.7	1.8
	11sk_skeletal
	muscle
	97497_Patient-	23.7	15.0
	11ut_uterus
	97498_Patient-	50.3	73.7
	11pl_placenta
	97500_Patient-	12.7	27.5
	12go_adipose
	97501_Patient-	2.8	8.4
	12sk_skeletal
	muscle
	97502_Patient-	18.4	27.7
	12ut_uterus
	97503_Patient-	68.8	75.8
	12pl_placenta
	94721_Donor 2	9.5	5.1
	U-A_Mesenchymal
	Stem Cells
	94722_Donor 2	3.3	3.5
	U-B_Mesenchymal
	Stem Cells
	94723_Donor 2	2.3	3.7
	U-C_Mesenchymal
	Stem Cells
	94709_Donor 2 AM-	8.8	9.9
	A_adipose
	94710_Donor 2 AM-	5.2	8.7
	B_adipose
	94711_Donor 2 AM-	3.4	4.0
	C_adipose
	94712_Donor 2 AD-	7.6	11.6
	A_adipose
	94713_Donor 2 AD-	12.2	17.9
	B_adipose
	94714_Donor 2 AD-	12.9	12.5
	C_adipose
	94742_Donor 3 U-	1.1	2.3
	A_Mesenchymal Stem
	Cells
	94743_Donor 3 U-	1.9	2.0
	B_Mesenchymal Stem
	Cells
	94730_Donor 3 AM -	9.8	13.9
	A_adipose
	94731_Donor 3 AM -	6.8	8.1
	B_adipose
	94732_Donor 3 AM -	9.0	8.8
	C_adipose
	94733_Donor 3 AD -	15.3	19.1
	A_adipose
	94734_Donor 3 AD -	7.1	10.6
	B_adipose
	94735_Donor 3 AD -	10.3	13.5
	C_adipose
	77138_Liver_HepG2untr	23.3	20.9
	eated
	73556_Heart_Cardiac	7.2	4.4
	stromal cells (primary)
	81735_Small Intestine	15.5	23.0
	72409_Kidney_Proximal	5.6	8.1
	Convoluted Tubule
	82685_Small	28.1	28.3
	intestine_Duodenum
	90650_Adrenal_Adrenoc	4.9	8.0
	ortical adenoma
	72410_Kidney_HRCE	25.0	28.1
	72411_Kidney_HRE	22.4	26.1
	73139_Uterus_Uterine	1.4	1.8
	smooth muscle cells

[1129] AI_comprehensive panel_v1.0 Summary: Ag4716 This gene is expressed at moderate to high levels in the majority of tissues on this panel, with highest expression in an osteoarthritic bone sample (CT=26.6). Clusters of higher expression of this gene are associated with samples from osteoarthritis and rheumatoid arthritis patients. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of arthritis. See Panel 4.1D for additional discussion of this gene in immune response.

[1130] General_screening_panel_v1.4 Summary: Ag4705/Ag4716 Three experiments using two probe-primer sets gave results that are in good agreement. This gene is expressed at moderate to high levels in all of the tissues on this panel. Interestingly, expression of this gene is higher in fetal lung and lung cancer cell lines when compared to adult lung. Expression of this gene is also upregulated in colon cancer cell lines when compared to normal colon. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of lung and colon cancer.

[1131] In addition, this gene is expressed at moderate levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[1132] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[1133] General_screening_panel_v1.5 Summary: Ag5877 Expression of the CG98102-04 gene is highest in bladder (CT=23.6). This gene is expressed at moderate to high levels in all of the tissues on this panel, consistent with what is observed in Panel 1.4. Interestingly, expression of this gene is higher in fetal lung (CT=23.7)and a subset of lung cancer cell lines (CTs=24) when compared to adult lung (CT=28.2). Expression of this gene is also upregulated in colon cancer cell lines (CTs=24) when compared to normal colon (CT=27.2). Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of lung and colon cancer. See Panel 1.4 for additional discussion of this gene in human disease.

[1134] Panel 4.1D Summary: Ag4716 Expression of the CG98102-04 gene is highest in LPS-treated monocytes (CT=25.8), with lower expression in resting monocytes (CT=31.4). Therefore, expression of this gene could be used to distinguish resting and activated monocytes. The expression of this transcript in LPS-treated monocytes, cells that play a crucial role in linking innate immunity to adaptive immunity, suggests a role for this gene product in initiating inflammatory reactions. Thus, therapeutic modulation of the activity of this gene or its protein product may reduce or prevent early stages of inflammation and reduce the severity of inflammatory diseases such as psoriasis, asthma, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis and other lung inflammatory diseases.

[1135] Expression of this gene is also upregulated in TNF-alpha/LPS-treated neutrophils (CT=25.8) compared to resting neutrophils (CT=27.7). Thus, the gene product may increase activation of these inflammatory cells and therapeutic modulation of the activity of this gene may be of benefit in the treatment of Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, lupus erythematosus, or psoriasis.

[1136] The CG98102-04 gene is also highly expressed in a cluster of treated and untreated samples derived from the NCI-H292 cell line, a human airway epithelial cell line that produces mucins. Mucus overproduction is an important feature of bronchial asthma and chronic obstructive pulmonary disease. The transcript is also expressed at lower but still significant levels in small airway epithelium treated with IL-1 beta and TNF-alpha. The expression of the transcript in this mucoepidermoid cell line that is often used as a model for airway epithelium (NCI-H292 cells) suggests that this transcript may be important in the proliferation or activation of airway epithelium. Therefore, therapeutics designed with the protein encoded by the transcript may reduce or eliminate symptoms caused by inflammation in lung epithelia in chronic obstructive pulmonary disease, asthma, allergy, and emphysema.

[1137] The CG98102-04 gene encodes a splice variant of diamine acetyltransferase, also known as spermidine/spermine N(1)-acetyltransferase (SPD/SPM acetyltransferase). Diamine acetyltransferase is a rate-limiting enzyme in the catabolic pathway of polyamine metabolism. It catalyzes the N(1)-acetylation of spermidine and spermine and, by the successive activity of polyamine oxidase, spermine can be converted to spermidine and spermidine to putrescine. The role of spermine in inflammation was reviewed by Zhang et al. [Crit Care Med. Apr. 28, 2000(4 Suppl):N60-6, PMID 10807317]. Regenerating tissues produce higher levels of spermine, and injured or dying cells release spermine into the extracellular milieu, so that tissue levels increase significantly at inflammatory sites of infection or injury. Recent research has focused on delineating the significance of spermine accumulation in the inflammatory process. The discovery that spermine is a negative regulator of macrophage activation provided a mechanism by which spermine influences the biology of inflammation. Mechanistic studies indicate that spermine is incorporated into macrophages and restrains the innate immune response.

[1138] Panel 5D Summary: Ag4705/Ag4716 Two experiments using two probe-primer sets gave results that are in good agreement. The CG98102-04 gene is expressed at moderate to high levels in the majority of metabolic tissues on this panel, with highest expression in a placenta sample from a diabetic patient (CTs=23-25).

[1139] Spermine has been demonstrated to enhance insulin receptor binding in a dose dependent manner [Pedersen et al., Mol Cell Endocrinol., April 1989;62(2):161-6]. Thus, it was proposed that polyamines may act as intracellular or intercellular (autocrine) regulators to modulate insulin binding. It has also been shown that the insulin-like effects elicited by polyamines in fat cells (e.g. enhancement of glucose transport and inhibition of cAMP-mediated lipolysis) are dependent on H2O2 production [Livingston et al., J. Biol. Chem., Jan. 25, 1977;252(2):560-2. Inhibiting polyamine catabolism through an inhibitor of this rate-limiting enzyme may abolish the insulin-like antilipolytic effects of polyamines. Therefore, therapeutic inhibition of the activity of this gene using small molecule drugs may be of benefit in the treatment of obesity.

[1140] AU. CG122909-01: Ubiquitin Protein Ligase

[1141] Expression of gene CG122909-01 was assessed using the primer-probe set Ag4553, described in Table AUA. Results of the RTQ-PCR runs are shown in Tables AUB and AUC.

TABLE AUA
Probe Name Ag4553
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-gcagattggcagagaaatactg-3′	22	2366	349
Probe	TET-5′-acaagaaacagcaagcaaatcatttg-3′-	26	2402	350
	TAMRA
Reverse	5′-ctctttcacaaactgccaaaac-3′	22	2428	351

[1142]

TABLE AUB
Oncology_cell_line_screening_panel_v3.1
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4553,		Ag4553,
	Run		Run
Tissue Name	224053074	Tissue Name	224053074
Daoy	7.3	Ca Ski_Cervical epidermoid	80.7
Medulloblastoma/Cerebellum		carcinoma (metastasis)
TE671	10.9	ES-2_Ovarian clear cell	22.8
Medulloblastom/Cerebellum		carcinoma
D283 Med	87.1	Ramos/6h stim_Stimulated with	21.8
Medulloblastoma/Cerebellum		PMA/ionomycin 6h
PFSK-1 Primitive	14.0	Ramos/14h stim_Stimulated	13.0
Neuroectodermal/Cerebellum		with PMA/ionomycin 14h
XE-498_CNS	33.9	MEG-01_Chronic myelogenous	40.3
		leukemia (megokaryoblast)
SNB-78_CNS/glioma	22.4	Raji_Burkitt's lymphoma	3.3
SF-268_CNS/glioblastoma	9.5	Daudi_Burkitt's lymphoma	12.4
T98G_Glioblastoma	17.0	U266_B-cell	22.2
		plasmacytoma/myeloma
SK-N-SH_Neuroblastoma	17.7	CA46_Burkitt'lymphoma	7.1
(metastasis)
SF-295_CNS/glioblastoma	27.4	RL_non-Hodgkin's B-cell	4.7
		lymphoma
Cerebellum	87.1	JM1_pre-B-cell	9.1
		lymphoma/leukemia
Cerebellum	5.3	Jurkat_T cell leukemia	25.9
NCI-H292_Mucoepidermoid	87.7	TF-1_Erythroleukemia	45.1
lung ca.
DMS-114_Small cell lung	8.5	HUT 78_T-cell lymphoma	23.2
cancer
DMS-79_Small cell lung	23.5	U937_Histiocytic lymphoma	5.0
cancer/neuroendocrine
NCI-H146_Small cell lung	24.5	KU-812_Myelogenous	23.8
cancer/neuroendocrine		leukemia
NCI-H526_Small cell lung	34.4	769-P_Clear cell renal ca.	47.6
cancer/neuroendocrine
NCI-N417_Small cell lung	11.7	Caki-2_Clear cell renal ca.	23.3
cancer/neuroendocrine
NCI-H82_Small cell lung	17.9	SW 839_Clear cell renal ca.	17.4
cancer/neuroendocrine
NCI-H157_Squamous cell lung	32.3	G401_Wilms' tumor	9.5
cancer (metastasis)
NCI-H1155_Large cell lung	78.5	Hs766T_Pancreatic ca. (LN	29.1
cancer/neuroendocrine		metastasis)
NCI-H1299_Large cell lung	72.7	CAPAN-1_Pancreatic	49.3
cancer/neuroendocrine		adenocarcinoma (liver
		metastasis)
NCI-H727_Lung carcinoid	48.0	SU86.86_Pancreatic carcinoma	59.9
		(liver metastasis)
NCI-UMC-11_Lung carcinoid	100.0	BxPC-3_Pancreatic	20.2
		adenocarcinoma
LX-1_Small cell lung cancer	10.8	HPAC_Pancreatic	97.3
		adenocarcinoma
Colo-205_Colon cancer	19.8	MIA PaCa-2_Pancreatic ca.	5.4
KM12_Colon cancer	24.5	CFPAC-1_Pancreatic ductal	52.9
		adenocarcinoma
KM20L2_Colon cancer	17.4	PANC-1_Pancreatic epithelioid	43.5
		ductal ca.
NCI-H716_Colon cancer	47.3	T24_Bladder ca. (transitional	13.7
		cell)
SW-48_Colon adenocarcinoma	32.5	5637_Bladder ca.	19.6
SW1116_Colon adenocarcinoma	6.1	HT-1197_Bladder ca.	52.1
LS 174T_Colon adenocarcinoma	21.5	UM-UC-3_Bladder ca.	9.8
		(transitional cell)
SW-948_Colon adenocarcinoma	7.1	A204_Rhabdomyosarcoma	5.8
SW-480_Colon adenocarcinoma	16.3	HT-1080_Fibrosarcoma	23.2
NCI-SNU-5_Gastric ca.	14.2	MG-63_Osteosarcoma (bone)	16.5
KATO III_Stomach	41.8	SK-LMS-1_Leiomyosarcoma	31.2
		(vulva)
NCI-SNU-16_Gastric ca.	35.8	SJRH30_Rhabdomyosarcoma	25.7
		(met to bone marrow)
NCI-SNU-1_Gastric ca.	41.2	A431_Epidermoid ca.	28.9
RF-1_Gastric adenocarcinoma	13.9	WM266-4_Melanoma	10.5
RF-48_Gastric adenocarcinoma	12.1	DU 145_Prostate	39.2
MKN-45_Gastric ca.	11.4	MDA-MB-468_Breast	20.3
		adenocarcinoma
NCI-N87_Gastric ca.	46.3	SSC-4_Tongue	25.3
OVCAR-5_Ovarian ca.	12.4	SSC-9_Tongue	50.7
RL9S-2_Uterine carcinoma	12.2	SSC-15_Tongue	62.4
HelaS3_Cervical	23.3	CAL 27_Squamous cell ca. of	25.5
adenocarcinoma		tongue

[1143]

TABLE AUC
Panel 4.1D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4553,		Ag4553,
	Run		Run
Tissue Name	203039492	Tissue Name	203039492
Secondary Th1 act	43.2	HUVEC IL-1beta	22.1
Secondary Th2 act	51.1	HUVEC IFN gamma	30.6
Secondary Tr1 act	35.1	HUVEC TNF alpha + IFN gamma	15.6
Secondary Th1 rest	25.2	HUVEC TNF alpha + IL4	14.8
Secondary Th2 rest	44.8	HUVEC IL-11	17.3
Secondary Tr1 rest	16.7	Lung Microvascular EC none	100.0
Primary Th1 act	14.8	Lung Microvascular EC	39.2
		TNFalpha + IL-1beta
Primary Th2 act	43.8	Microvascular Dermal EC none	36.3
Primary Tr1 act	40.1	Microvascular Dermal EC	24.0
		TNFalpha + IL-1beta
Primary Th1 rest	15.9	Bronchial epithelium TNFalpha +	34.2
		IL1beta
Primary Th2 rest	11.9	Small airway epithelium none	15.3
Primary Tr1 rest	31.9	Small airway epithelium	45.1
		TNFalpha + IL-1beta
CD45RA CD4 lymphocyte act	30.1	Coronery artery SMC rest	15.1
CD45RO CD4 lymphocyte act	50.7	Coronery artery SMC TNFalpha +	14.5
		IL-1beta
CD8 lymphocyte act	27.7	Astrocytes rest	8.6
Secondary CD8 lymphocyte	39.5	Astrocytes TNFalpha + IL-1beta	9.7
rest
Secondary CD8 lymphocyte act	12.0	KU-812 (Basophil) rest	22.7
CD4 lymphocyte none	29.9	KU-812 (Basophil)	33.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	48.6	CCD1106 (Keratinocytes) none	32.3
CH11
LAK cells rest	22.1	CCD1106 (Keratinocytes)	23.5
		TNFalpha + IL-1beta
LAK cells IL-2	30.8	Liver cirrhosis	15.8
LAK cells IL-2 + IL-12	14.7	NCI-H292 none	31.6
LAK cells IL-2 + IFN gamma	13.3	NCI-H292 IL-4	49.0
LAK cells IL-2 + IL-18	16.4	NCI-H292 IL-9	57.8
LAK cells PMA/ionomycin	23.8	NCI-H292 IL-13	38.4
NK Cells IL-2 rest	41.5	NCI-H292 IFN gamma	27.7
Two Way MLR 3 day	30.6	HPAEC none	17.1
Two Way MLR 5 day	25.2	HPAEC TNF alpha + IL-1 beta	31.0
Two Way MLR 7 day	15.4	Lung fibroblast none	13.9
PBMC rest	23.0	Lung fibroblast TNF alpha + IL-1	12.9
		beta
PBMC PWM	22.7	Lung fibroblast IL-4	16.6
PBMC PHA-L	22.4	Lung fibroblast IL-9	29.1
Ramos (B cell) none	24.1	Lung fibroblast IL-13	17.0
Ramos (B cell) ionomycin	23.8	Lung fibroblast IFN gamma	24.1
B lymphocytes PWM	23.7	Dermal fibroblast CCD1070 rest	20.0
B lymphocytes CD40L and IL-	18.2	Dermal fibroblast CCD1070 TNF	37.9
4		alpha
EOL-1 dbcAMP	21.3	Dermal fibroblast CCD1070 IL-1	13.7
		beta
EOL-1 dbcAMP	19.5	Dermal fibroblast IFN gamma	8.9
PMA/ionomycin
Dendritic cells none	23.3	Dermal fibroblast IL-4	31.0
Dendritic cells LPS	13.3	Dermal Fibroblast rest	11.1
Dendritic cells anti-CD40	14.7	Neutrophils TNFa + LPS	0.4
Monocytes rest	27.2	Neutrophils rest	3.4
Monocytes LPS	15.5	Colon	9.9
Macrophages rest	22.1	Lung	20.9
Macrophages LPS	7.2	Thymus	24.8
HUVEC none	19.5	Kidney	59.5
HUVEC starved	23.7

[1144] Oncology_cell_line_screening_panel_v3.1 Summary: Ag4553 Highest expression of this gene is seen in a lung cancer cell line (CT=29). In addition, this gene is ubiquitously expressed in all the samples on this panel. Thus, modulation of this gene may be of use in the treatment of cancer.

[1145] Panel 4.1D Summary: Ag4553 Highest expression of this gene is seen in untreated lung microvascular endothelial cells (CT=28.5). In addition, this gene is also expressed at moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

Example D

Identification of Single Nucleotide Polymorphisms in NOVX Nucleic Acid Sequences

[1146] Variant sequences are also included in this application. A variant sequence can include a single nucleotide polymorphism (SNP). A SNP can, in some instances, be referred to as a “cSNP” to denote that the nucleotide sequence containing the SNP originates as a cDNA. A SNP can arise in several ways. For example, a SNP may be due to a substitution of one nucleotide for another at the polymorphic site. Such a substitution canbe either a transition or a transversion. A SNP can also arise from a deletion of a nucleotide or an insertion of a nucleotide, relative to a reference allele. In this case, the polymorphic site is a site at which one allele bears a gap with respect to a particular nucleotide in another allele. SNPs occurring within genes may result in an alteration of the amino acid encoded by the gene at the position of the SNP. Intragenic SNPs may also be silent, when a codon including a SNP encodes the same amino acid as a result of the redundancy of the genetic code. SNPs occurring outside the region of a gene, or in an intron within a gene, do not result in changes in any amino acid sequence of a protein but may result in altered regulation of the expression pattern. Examples include alteration in temporal expression, physiological response regulation, cell type expression regulation, intensity of expression, and stability of transcribed message.

[1147] SeqCalling assemblies produced by the exon linking process were selected and extended using the following criteria. Genomic clones having regions with 98% identity to all or part of the initial or extended sequence were identified by BLASTN searches using the relevant sequence to query human genomic databases. The genomic clones that resulted were selected for further analysis because this identity indicates that these clones contain the genomic locus for these SeqCalling assemblies. These sequences were analyzed for putative coding regions as well as for similarity to the known DNA and protein sequences. Programs used for these analyses include Grail, Genscan, BLAST, HMMER, FASTA, Hybrid and other relevant programs.

[1148] Some additional genomic regions may have also been identified because selected SeqCalling assemblies map to those regions. Such SeqCalling sequences may have overlapped with regions defined by homology or exon prediction. They may also be included because the location of the fragment was in the vicinity of genomic regions identified by similarity or exon prediction that had been included in the original predicted sequence. The sequence so identified was manually assembled and then may have been extended using one or more additional sequences taken from CuraGen Corporation's human SeqCalling database. SeqCalling fragments suitable for inclusion were identified by the CuraTools™ program SeqExtend or by identifying SeqCalling fragments mapping to the appropriate regions of the genomic clones analyzed.

[1149] The regions defined by the procedures described above were then manually integrated and corrected for apparent inconsistencies that may have arisen, for example, from miscalled bases in the original fragments or from discrepancies between predicted exon junctions, EST locations and regions of sequence similarity, to derive the final sequence disclosed herein. When necessary, the process to identify and analyze SeqCalling assemblies and genomic clones was reiterated to derive the full length sequence (Alderborn et al., Determination of Single Necleotide Polymorphisms by Real-time Pyrophosphate DNA Sequencing. Genome Research. 10 (8) 1249-1265, 2000).

[1150] Variants are reported individually but any combination of all or a select subset of variants are also included as contemplated NOVX embodiments of the invention.

[1151] NOV2 SNP Data CG103679-02

[1152] Six polymorphic variants of NOV2 have been identified and are shown in Table 1S.

	TABLE 1S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position			Position
No.	of SNP	Wild-type	Variant	of SNP	Wild-type	Variant
13379494	25	T	C	4	Ile	Ile
13376778	77	C	T	22	Arg	End
13376779	262	T	C	83	Asp	Asp
13376780	307	A	G	98	Ile	Met
13376781	359	T	C	116	Phe	Leu
13379451	800	G	A	263	Gly	Ser

[1153] NOV4 SNP Data CG110223-02

[1154] One polymorphic variant of NOV4 has been identified and is shown in Table 2S.

	TABLE 2S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position			Position
No.	of SNP	Wild-type	Variant	of SNP	Wild-type	Variant
13379318	685	C	A	223	Leu	Ile

[1155] NOV5 SNP Data CG110311-01

[1156] Two polymorphic variants of NOV5 have been identified and are shown in Table 3S.

	TABLE 3S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position			Position
No.	of SNP	Wild-type	Variant	of SNP	Wild-type	Variant
13379328	1796	C	T	589	Ala	Val
13379327	1939	G	A	637	Gly	Arg

[1157] NOV6 SNP Data CG110421-02

[1158] Three polymorphic variants of NOV6 have been identified and are shown in Table 4S.

	TABLE 4S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position			Position
No.	of SNP	Wild-type	Variant	of SNP	Wild-type	Variant
13375879	569	T	C	170	Ile	Thr
13375878	601	C	T	181	Pro	Ser
13375877	637	A	G	193	Thr	Ala

[1159] NOV7 SNP Data CG110531-01

[1160] One polymorphic variant of NOV7 has been identified and is shown in Table 5S.

	TABLE 5S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position			Position
No.	of SNP	Wild-type	Variant	of SNP	Wild-type	Variant
43	C	T	0

[1161] NOV9 SNP Data CG111293-05

[1162] Three polymorphic variants of NOV9 have been identified and are shown in Table 6S.

	TABLE 6S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13379350	881	T	C	202	Leu	Leu
13379341	1329	T	C	351	Leu	Pro
13379340	1433	A	G	386	Thr	Ala

[1163] NOV13 SNP Data CG112881-02

[1164] One polymorphic variant of NOV13 has been identified and is shown in Table 7S.

	TABLE 7S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13379428	834	T	C	92	Leu	Leu

[1165] NOV14 SNP Data CG113803-01

[1166] Three polymorphic variants of NOV14 have been identified and are shown in Table 8S.

	TABLE 8S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13379373	3197	T	C	1012	Val	Ala
13379374	4891	C	T	1577	Leu	Leu
13379375	4994	G	A	1611	Gly	Asp

[1167] NOV17 SNP Data CG114555-01

[1168] Four polymorphic variants of NOV17 have been identified and are shown in Table 9S.

	TABLE 9S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13379365	86	G	A	25	Gly	Arg
13379364	97	G	A	28	Gly	Gly
13379363	289	A	G	92	Thr	Thr
13379362	672	C	T	220	Pro	Leu

[1169] NOV20 SNP Data CG115411-01

[1170] One polymorphic variant of NOV20 has been identified and is shown in Table 10S.

	TABLE 10S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13379493	5601	G	A	1839	Val	Met

[1171] NOV21 SNP Data CG116270-01

[1172] One polymorphic variant of NOV21 has been identified and is shown in Table 11S.

	TABLE 11S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13379368	218	A	G	49	Gln	Arg

[1173] NOV22 SNP Data CG118160-01

[1174] Three polmorphic variants of NOV22 have been identified and are shown in Table 12S.

	TABLE 12S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13379361	3883	A	G	1275	Ser	Gly
13379360	3912	C	T	1284	Thr	Thr
13379359	4262	A	G	1401	Glu	Gly

[1175] NOV24 SNP Data CG120443-01

[1176] Two polymorphic variants of NOV24 have been identified and are shown in Table 13S.

	TABLE 13S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13379473	1561	A	G	505	Arg	Gly
13379480	2103	C	T	685	Pro	Pro

[1177] NOV25 SNP Data CG120563-01

[1178] Five polymorphic variants of NOV25 have been identified and are shown in Table 14 S.

	TABLE 14S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13379471	325	A	G	70	Ser	Gly
13379470	377	T	C	87	Ile	Thr
13379469	390	T	C	91	Cys	Cys
13379468	3131	G	T	1005	Cys	Phe
13379467	3202	G	A	0

[1179] NOV27 SNP Data CG122909-01

[1180] One polymorphic variant of NOV27 has been identified and is shown in Table 15S.

	TABLE 15S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13379466	2645	G	A	879	Glu	Lys

[1181] NOV28 SNP Data CG123772-01

[1182] One polymorphic variant of NOV28 has been identified and is shown in Table 16S.

	TABLE 16S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
c100.191	1057	A	G	349	Thr	Thr

[1183] NOV29 SNP Data CG124021-01

[1184] Six polymorphic variants of NOV29 have been identified and are shown in Table 17S.

	TABLE 17S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13375963	363	G	A	29	Glu	Lys
13375964	423	A	G	49	Ile	Val
13375969	759	G	A	161	Glu	Lys
13375968	921	T	C	215	Phe	Leu
13375967	946	T	C	223	Leu	Pro
13375966	952	A	G	225	Gln	Arg

[1185] NOV31 SNP Data CG55814-02

[1186] Six polymorphic variants of NOV31 have been identified and are shown in Table 18S.

	TABLE 18S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13376338	414	T	C	127	Asp	Asp
13376352	683	A	G	217	Asn	Ser
13376347	839	A	G	269	His	Arg
13376346	852	T	C	273	Phe	Phe
13379452	909	T	C	292	Tyr	Tyr
13379475	1054	C	A	0

[1187] NOV32 SNP Data CG56735-01

[1188] Three polymorphic variants of NOV32 have been identified and are shown in Table 19S.

	TABLE 19S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13379196	861	A	G	259	Lys	Lys
13379195	871	A	G	263	Lys	Glu
13374732	1425	C	T	447	Asp	Asp

[1189] NOV33 SNP Data CG57635-02

[1190] Three polymorphic variants of NOV33 have been identified and are shown in Table 20S.

	TABLe 20S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13379472	147	G	A	47	Met	Ile
C110.6584	590	A	G	195	Tyr	Cys
C110.5945	1037	C	T	344	Ala	Val

[1191] NOV34 SNP Data CG96859-02

[1192] Three polymorphic variants of NOV34 have been identified and are shown in Table 21S.

	TABLE 21S
	Nucleotides	Amino Acids
	Base			Base
Variant	Position of	Wild-		Position of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13376166	455	G	A	147	Leu	Leu
13379476	512	C	T	166	Thr	Thr
cg111.7782	528	G	A	172	Ala	Thr

Example E

Expression of NOV2 (CG103679-07)

[1193] Construction of the Mammalian Expression Vector pCEP4/Sec.

[1194] The oligonucleotide primers, pSec-V5-His Forward (CTCGTCCTCGAGGGTAAGCCTATCCCTAAC; SEQ ID NO: 352) and the pSec-V5-His Reverse (CTCGTCGGGCCCCTGATCAGCGGGTTTAAAC; SEQ ID NO: 353), were designed to amplify a fragment from the pcDNA3.1-V5His (Invitrogen, Carlsbad, Calif.) expression vector. The PCR product was digested with XhoI and ApaI and ligated into the XhoI/ApaI digested pSecTag2 B vector (Invitrogen, Carlsbad Calif.). The correct structure of the resulting vector, pSecV5His, was verified by DNA sequence analysis. The vector pSecV5His was digested with PmeI and NheI, and the PmeI-NheI fragment was ligated into the BamHI/Klenow and NheI treated vector pCEP4 (Invitrogen, Carlsbad, Calif.). The resulting vector was named as pCEP4/Sec.

[1195] Expression of CG103679-07 in human embryonic kidney 293 cells. A 936 bp BamHI-XhoI fragment containing the CG103679-07 sequence was subcloned into Bg1 II-XhoI digested pCEP4/Sec to generate plasmid 1348. The plasmid 1348 was transfected into 293 cells using the LipofectaminePlus reagent following the manufacturer's instructions (Gibco/BRL). The cell pellet and supernatant were harvested 72 h post transfection and examined for CG103679-07 expression by Western blot (reducing conditions) using an anti-V5 antibody. CG103679-07 is expressed as a 45 kDa protein secreted by 293 cells.

Example F

Studies of the NOV36 Diamine Acetyltransferase

[1196] The following sections describe the study design(s) and the techniques used to identify the Diamine Acetyltransferase—encoded protein and any variants, thereof, as being suitable as diagnostic markers, targets for an antibody therapeutic and targets for a small molecule drugs for Obesity and Diabetes.

[1197] Studies: MB.08 Human Mesenchymal Stem Cell Differentiation

[1198] Study Statements: Bone marrow-derived human mesenchymal stem cells have the capacity to differentiate into muscle, adipose, cartilage and bone. Culture conditions have been established that permit the differentiation in vitro along the pathway to adipose, cartilage and bone. Understanding the gene expression changes that accompany these distinct differentiation processes would be of considerable biologic value. Regulation of adipocyte differentiation would have importance in the treatment of obesity, diabetes and hypertension. Human mesenchymal stem cells from 3 donors were obtained and differentiated in vitro according to published methods. RNA from samples of the undifferentiated, mid-way differentiated and fully differentiated cells was isolated for analysis of differential gene expression.

[1199] Species #1 Humans

[1200] Studies: BP24.02 Mouse Dietary—Induced Obesity

[1201] Study Statements: The predominant cause for obesity in clinical populations is excess caloric intake. This so-called diet-induced obesity (DIO) is mimicked in animal models by feeding high fat diets of greater than 40% fat content. The DIO study was established to identify the gene expression changes contributing to the development and progression of diet-induced obesity. In addition, the study design seeks to identify the factors that lead to the ability of certain individuals to resist the effects of a high fat diet and thereby prevent obesity. The sample groups for the study had body weights +1 S.D., +4 S.D. and +7 S.D. of the chow-fed controls (below). In addition, the biochemical profile of the +7 S.D. mice revealed a further stratification of these animals into mice that retained a normal glycemic profile in spite of obesity and mice that demonstrated hyperglycemia. Tissues examined included hypothalamus, brainstem, liver, retroperitoneal white adipose tissue (WAT), epididymal WAT, brown adipose tissue (BAT), gastrocnemius muscle (fast twitch skeletal muscle) and soleus muscle (slow twitch skeletal muscle). The differential gene expression profiles for these tissues should reveal genes and pathways that can be used as therapeutic targets for obesity.

[1202] Species #2 mouse

[1203] SPECIES #1 A gene fragment of the human Diaamine Acetyltransferase was initially found to be up-regulated by 1.6 fold in the Mid-Way adipocyte versus Mesenchymal stem cells using CuraGen's GeneCalling™ method of differential gene expression. In another experiment this gene was found to be up-regulated by 2.4 fold in adipocyte versus mesenchymal stem. A differentially expressed human gene fragment was definitively identified as a component of the Diamine Acetyltransferase cDNA. The method of comparative PCR was used for confirmation of the gene assessment. The electropherographic peaks corresponding to the gene fragment of the Diamine Acetyltransferase are ablated when a gene-specific primer competes with primers in the linker-adaptors during the PCR amplification.

[1204] SPECIES #2 A gene fragment of the mouse Diamine Acetyltransferase was also found to be up-regulated by 1.6 to 1.8 fold in the ngsd 7 efp-, rfp-, and brown adipose tissue as compared to respective tissues from Chow fed mice (See Table F1). A differentially expressed mouse gene fragment was definitively identified as a component of the mouse diamine acetyltransferase cDNA. The method of comparative PCR was used for conformation of the gene assessment.

TABLE F1
This differentially expressed gene fragment in Discovery
Study 24.02 identified in ngsd7-BAT versus chow-BAT,
is from the Diamine Acetyltransferase.
	Study	Description	Fold
	DIO:	ngsd7-efp adipose versus sd1-efp adipose	+1.8
		ngsd7-rfp adipose versus chow-rfp adipose	+1.8
		ngsd7-rfp adipose versus sd1-rfp adipose	+1.7
		ngsd7-brown adipose versus chow-brown adipose	+1.6

OTHER EMBODIMENTS

[1205] Although particular embodiments have been disclosed herein in detail, this has been done by way of example for purposes of illustration only, and is not intended to be limiting with respect to the scope of the appended claims, which follow. In particular, it is contemplated by the inventors that various substitutions, alterations, and modifications may be made to the invention without departing from the spirit and scope of the invention as defined by the claims. The choice of nucleic acid starting material, clone of interest, or library type is believed to be a matter of routine for a person of ordinary skill in the art with knowledge of the embodiments described herein. Other aspects, advantages, and modifications considered to be within the scope of the following claims. The claims presented are representative of the inventions disclosed herein. Other, unclaimed inventions are also contemplated. Applicants reserve the right to pursue such inventions in later claims.

Claims

1. An isolated polypeptide comprising the mature form of an amino acid sequenced selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 78.

2. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 78.

3. An isolated polypeptide comprising an amino acid sequence which is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 78.

4. An isolated polypeptide, wherein the polypeptide comprises an amino acid sequence comprising one or more conservative substitutions in the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 78.

5. The polypeptide of claim 1 wherein said polypeptide is naturally occurring.

6. A composition comprising the polypeptide of claim 1 and a carrier.

7. A kit comprising, in one or more containers, the composition of claim 6.

8. The use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, the disease selected from a pathology associated with the polypeptide of claim 1, wherein the therapeutic comprises the polypeptide of claim 1.

9. A method for determining the presence or amount of the polypeptide of claim 1 in a sample, the method comprising: (a) providing said sample; (b) introducing said sample to an antibody that binds immunospecifically to the polypeptide; and (c) determining the presence or amount of antibody bound to said polypeptide, thereby determining the presence or amount of polypeptide in said sample.

10. A method for determining the presence of or predisposition to a disease associated with altered levels of expression of the polypeptide of claim 1 in a first mammalian subject, the method comprising: a) measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and b) comparing the expression of said polypeptide in the sample of step (a) to the expression of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, said disease, wherein an alteration in the level of expression of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to said disease.

11. A method of identifying an agent that binds to the polypeptide of claim 1, the method comprising: (a) introducing said polypeptide to said agent; and (b) determining whether said agent binds to said polypeptide.

12. The method of claim 11 wherein the agent is a cellular receptor or a downstream effector.

13. A method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions of the polypeptide of claim 1, the method comprising: (a) providing a cell expressing the polypeptide of claim 1 and having a property or function ascribable to the polypeptide; (b) contacting the cell with a composition comprising a candidate substance; and (c) determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition in the absence of the substance, the substance is identified as a potential therapeutic agent.

14. A method for screening for a modulator of activity of or of latency or predisposition to a pathology associated with the polypeptide of claim 1, said method comprising: (a) administering a test compound to a test animal at increased risk for a pathology associated with the polypeptide of claim 1, wherein said test animal recombinantly expresses the polypeptide of claim 1;(b) measuring the activity of said polypeptide in said test animal after administering the compound of step (a); and (c) comparing the activity of said polypeptide in said test animal with the activity of said polypeptide in a control animal not administered said polypeptide, wherein a change in the activity of said polypeptide in said test animal relative to said control animal indicates the test compound is a modulator activity of or latency or predisposition to, a pathology associated with the polypeptide of claim 1.

15. The method of claim 14, wherein said test animal is a recombinant test animal that expresses a test protein transgene or expresses said transgene under the control of a promoter at an increased level relative to a wild-type test animal, and wherein said promoter is not the native gene promoter of said transgene.

16. A method for modulating the activity of the polypeptide of claim 1, the method comprising contacting a cell sample expressing the polypeptide of claim 1 with a compound that binds to said polypeptide in an amount sufficient to modulate the activity of the polypeptide.

17. A method of treating or preventing a pathology associated with the polypeptide of claim 1, the method comprising administering the polypeptide of claim 1 to a subject in which such treatment or prevention is desired in an amount sufficient to treat or prevent the pathology in the subject.

18. The method of claim 17, wherein the subject is a human.

19. A method of treating a pathological state in a mammal, the method comprising administering to the mammal a polypeptide in an amount that is sufficient to alleviate the pathological state, wherein the polypeptide is a polypeptide having an amino acid sequence at least 95% identical to a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 78 or a biologically active fragment thereof.

20. An isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78.

21. The nucleic acid molecule of claim 20, wherein the nucleic acid molecule is naturally occurring.

22. A nucleic acid molecule, wherein the nucleic acid molecule differs by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 78.

23. An isolated nucleic acid molecule encoding the mature form of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 78.

24. An isolated nucleic acid molecule comprising a nucleic acid selected from the group consisting of 2n-1, wherein n is an integer between 1 and 78.

25. The nucleic acid molecule of claim 20, wherein said nucleic acid molecule hybridizes under stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 78, or a complement of said nucleotide sequence.

26. A vector comprising the nucleic acid molecule of claim 20.

27. The vector of claim 26, further comprising a promoter operably linked to said nucleic acid molecule.

28. A cell comprising the vector of claim 26.

29. An antibody that immunospecifically binds to the polypeptide of claim 1.

30. The antibody of claim 29, wherein the antibody is a monoclonal antibody.

31. The antibody of claim 29, wherein the antibody is a humanized antibody.

32. A method for determining the presence or amount of the nucleic acid molecule of claim 20 in a sample, the method comprising: (a) providing said sample; (b) introducing said sample to a probe that binds to said nucleic acid molecule; and (c) determining the presence or amount of said probe bound to said nucleic acid molecule, thereby determining the presence or amount of the nucleic acid molecule in said sample.

33. The method of claim 32 wherein presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type.

34. The method of claim 33 wherein the cell or tissue type is cancerous.

35. A method for determining the presence of or predisposition to a disease associated with altered levels of expression of the nucleic acid molecule of claim 20 in a first mammalian subject, the method comprising: a) measuring the level of expression of the nucleic acid in a sample from the first mammalian subject; and b) comparing the level of expression of said nucleic acid in the sample of step (a) to the level of expression of the nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of expression of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

36. A method of producing the polypeptide of claim 1, the method comprising culturing a cell under conditions that lead to expression of the polypeptide, wherein said cell comprises a vector comprising an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78.

37. The method of claim 36 wherein the cell is a bacterial cell.

38. The method of claim 36 wherein the cell is an insect cell.

39. The method of claim 36 wherein the cell is a yeast cell.

40. The method of claim 36 wherein the cell is a mammalian cell.

41. A method of producing the polypeptide of claim 2, the method comprising culturing a cell under conditions that lead to expression of the polypeptide, wherein said cell comprises a vector comprising an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 78.

42. The method of claim 41 wherein the cell is a bacterial cell.

43. The method of claim 41 wherein the cell is an insect cell.

44. The method of claim 41 wherein the cell is a yeast cell.

45. The method of claim 41 wherein the cell is a mammalian cell.