Novel antibodies that bind to antigenic polypeptides, nucleic acids encoding the antigens, and methods of use

Abstract

Disclosed herein are nucleic acid sequences that encode polypeptides. Also disclosed are antibodies, which immunospecifically-bind to the polypeptide, as well as derivatives, variants, mutants, or fragments of the aforementioned polypeptide, polynucleotide, or antibody. 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, polypeptides, or antibodies, or fragments thereof.

Description

FIELD OF THE INVENTION

[0002] The present invention relates to novel antibodies that bind immunospecifically to antigenic polypeptides, wherein the polypeptides have characteristic properties related to biochemical or physiological responses in a cell, a tissue, an organ or an organism. The novel polypeptides are gene products of novel genes, or are specified biologically active fragments or derivatives thereof. Methods of use of the antibodies encompass procedures for diagnostic and prognostic assay of the polypeptides, as well as methods of treating diverse pathological conditions.

BACKGROUND OF THE INVENTION

[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 elevated or excessive synthesis and secretion of protein effectors. In a clinical setting a subject may be suspected of suffering from a condition brought on by elevated or excessive levels of a protein effector of interest.

[0007] Antibodies are multichain proteins that bind specifically to a given antigen, and bind poorly, or not at all, to substances deemed not to be cognate antigens. Antibodies are comprised of two short chains termed light chains and two long chains termed heavy chains. These chains are constituted of immunoglobulin domains, of which generally there are two classes: one variable domain per chain, one constant domain in light chains, and three or more constant domains in heavy chains. The antigen-specific portion of the immunoglobulin molecules resides in the variable domains; the variable domains of one light chain and one heavy chain associate with each other to generate the antigen-binding moiety. Antibodies that bind immunospecifically to a cognate or target antigen bind with high affinities. Accordingly, they are useful in assaying specifically for the presence of the antigen in a sample. In addition, they have the potential of inactivating the activity of the antigen.

[0008] Therefore there is a need to assay for the level of a protein effector of interest in a biological sample from such a subject, and to compare this level with that characteristic of a nonpathological condition. In particular, there is a need for such an assay based on the use of an antibody that binds immunospecifically to the antigen. There further is a need to inhibit the activity of the protein effector in cases where a pathological condition arises from elevated or excessive levels of the effector based on the use of an antibody that binds immunospecifically to the effector. Thus, there is a need for the antibody as a product of manufacture. There further is a need for a method of treatment of a pathological condition brought on by an elevated or excessive level of the protein effector of interest based on administering the antibody to the subject.

SUMMARY OF THE INVENTION

[0009] The invention is based in part upon the discovery of nucleic acid sequences encoding novel polypeptides. 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 or polypeptide sequences.

[0010] In one aspect, the invention provides an isolated polypeptide comprising a mature form of a NOVX amino acid. The polypeptide 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 NOVX polypeptides. In another aspect, the invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof.

[0011] Also included in the invention is a NOVX polypeptide that is a naturally occurring variant of a NOVX sequence. In one embodiment, the 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.

[0012] In another aspect, invention provides a method for determining the presence or amount of the NOVX polypeptide in a sample by 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.

[0013] In yet another aspect, the invention includes a method for determining the presence of or predisposition to a disease associated with altered levels of a NOVX polypeptide in a mammalian subject by 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. 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.

[0014] In another aspect, the invention includes pharmaceutical compositions that include therapeutically- or prophylactically-effective amounts of a therapeutic and a pharmaceutically-acceptable carrier. The therapeutic can be, e.g., a NOVX nucleic acid, a NOVX polypeptide, or an antibody specific for a NOVX polypeptide. In a further aspect, the invention includes, in one or more containers, a therapeutically- or prophylactically-effective amount of this pharmaceutical composition.

[0015] In still another aspect, the invention provides the use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease that is associated with a NOVX polypeptide.

[0016] In a further aspect, the invention provides a method for modulating the activity of a NOVX polypeptide by contacting a cell sample expressing the NOVX polypeptide with antibody that binds the NOVX polypeptide in an amount sufficient to modulate the activity of the polypeptide.

[0017] 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 46, or a complement of the nucleotide sequence. In one embodiment, the invention provides a nucleic acid molecule wherein the nucleic acid includes the nucleotide sequence of a naturally occurring allelic nucleic acid variant.

[0018] Also included in the invention is a vector containing one or more of the nucleic acids described herein, and a cell containing the vectors or nucleic acids described herein. The invention is also directed to host cells transformed with a vector comprising any of the nucleic acid molecules described above.

[0019] In yet another aspect, the invention provides for a method for determining the presence or amount of a nucleic acid molecule in a sample by contacting a sample with a probe that binds a NOVX nucleic acid and determining the amount of the probe that is bound to the NOVX nucleic acid. For example the NOVX nucleic may be a marker for cell or tissue type such as a cell or tissue type that is cancerous.

[0020] In yet a further aspect, the invention provides a method for determining the presence of or predisposition to a disease associated with altered levels of a nucleic acid molecule in a first mammalian subject, 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] The invention further provides an antibody that binds immunospecifically to a NOVX polypeptide. The NOVX antibody may be monoclonal, humanized, or a fully human antibody. Preferably, the antibody has a dissociation constant for the binding of the NOVX polypeptide to the antibody less than 1×10−9 M. More preferably, the NOVX antibody neutralizes the activity of the NOVX polypeptide.

[0022] In a further aspect, the invention provides for the use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, associated with a NOVX polypeptide. Preferably the therapeutic is a NOVX antibody.

[0023] In yet a further aspect, the invention provides a method of treating or preventing a NOVX-associated disorder, a method of treating a pathological state in a mammal, and a method of treating or preventing a pathology associated with a polypeptide by administering a NOVX antibody to a subject in an amount sufficient to treat or prevent the disorder.

[0024] 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 are not intended to be limiting.

[0025] Other features and advantages of the invention will be apparent from the following detailed description and claims.

DETAILED DESCRIPTION OF THE INVENTION

[0026] 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 1 provides a summary of the NOVX nucleic acids and their encoded polypeptides.

TABLE 1
NOVX Polynucleotide and Polypeptide
Sequences and Corresponding SEQ ID Numbers
		SEQ ID
		NO
NOVX		(nucleic	SEQ ID NO
Assignment	Internal Identification	acid)	(polypeptide)	Homology
1a	CG56258-01	1	2	Sodium/Calcium Exchanger
1b	CG56258-02	3	4	Sodium/Calcium Exchanger
1c	248057963	5	6	Sodium/Calcium Exchanger
2a	CG59843-01	7	8	Fibropellin III
3a	CG59845-01	9	10	Butyrophilin
4a	CG59871-01	11	12	CVB3 Binding Protein
5a	CG59883-01	13	14	CVB3 Binding Protein
6a	CG59901-01	15	16	Scavenger receptor
7a	CG88748-01	17	18	Cyclic Nucleotide-gated Channel
				Protein
8a	CG90021-01	19	20	Testicular Metalloprotease
				(Disintegrin)
9a	CG90709-01	21	22	Ion Transport Protein
9b	CG90709-02	23	24	Ion Transport Protein
9c	CG90709-03	25	26	Ion Transport Protein
9d	CG90709-04	27	28	Ion Transport Protein
10a	CG90739-01	29	30	Neuronal Thread Protein
10b	172390256	31	32	Neuronal Thread Protein
10c	172390440	33	34	Neuronal Thread Protein
10d	172390569	35	36	Neuronal Thread Protein
10e	172390587	37	38	Neuronal Thread Protein
10f	172390603	39	40	Neuronal Thread Protein
10g	172390624	41	42	Neuronal Thread Protein
10h	172390644	43	44	Neuronal Thread Protein
11a	CG91667-01	45	46	Delta-like Homology (dlk1)
11b	CG91667-02	47	48	Delta-like Homology (dlk1)
12a	CG92293-01	49	50	Polyprotein (ovochymase)
12b	CG92293-02	51	52	Polyprotein (ovochymase)
13a	CG92384-01	53	54	Long type PB-Cadherin
14a	CG92455-01	55	56	IGFBP
15a	CG92531-01	57	58	Leucine Rich
16a	CG92715-01	59	60	KIAA0918
16b	CG92715-02	61	62	Leucine Rich Repeat
17a	CG92813-01	63	64	Cadherin Related Tumor
				Suppressor Precursor
18a	CG92844-01	65	66	Thyroid Hormone Induced Protein
				B Precursor
18b	174308357	67	68	Thyroid Hormone lnduced Protein
				B Precursor
19a	CG93088-01	69	70	Monocarboxylate Transporter
20a	CG93335-01	71	72	Putative Type II Membrane
21a	CG93345-01	73	74	GPCR
22a	CG93400-01	75	76	GPCR
23a	CG93410-01	77	78	Glutamate Receptor 5 Precursor
23b	188822752	79	80	Glutamate Receptor 5 Precursor
24a	CG93722-01	81	82	Hepsin
25a	CG93858-01	83	84	Fibullin
25b	CG93858-02	85	86	Fibullin
25c	CG56914-03	87	88	Fibullin
26a	CG93871-01	89	90	Fibullin
27a	CG93884-01	91	92	Monocyte Inhibitory Receptor

[0027] Table 1 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 1 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 1.

[0028] 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.

[0029] Consistent with other known members of the family of proteins, identified in column 5 of Table 1, 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.

[0030] 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 1.

[0031] 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 B. 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.

[0032] Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.

NOVX Clones

[0033] 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.

[0034] 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.

[0035] The NOVX nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as research tools. 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.

[0036] 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 46; (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 46, 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 46; (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 46 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).

[0037] 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 46; (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 46 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 46; (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 46, 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 46 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.

[0038] 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 46; (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 46 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 46; 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 101 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.

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 mRNA's) 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, again by way of nonlimiting example, as a result of one or more naturally occurring processing steps as they may take place within the cell, or 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 “probes”, as utilized herein, refers to nucleic acid sequences of variable length, preferably between at least about 10 nucleotides (nt), 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- 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 utilized herein, is one, which 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 when produced by recombinant techniques, or of chemical precursors or other chemicals when chemically synthesized.

[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 1-46, or a complement of this aforementioned 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 1-46, 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 and 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, which oligonucleotide has a sufficient number of nucleotide bases to be used in a PCR reaction. 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 portions of 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 1-46, 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 SEQ ID NO:2n−1, wherein n is an integer between 1-46, 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 1-46, is one that is sufficiently complementary to the nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1-46, that it can hydrogen bond with little or no mismatches to the nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1-46, 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] Fragments provided herein are defined as sequences 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, respectively, and are 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. Derivatives are nucleic acid sequences or amino acid sequences formed from the native compounds either directly or by modification or partial substitution. Analogs are nucleic acid sequences or amino acid sequences that have a structure similar to, but not identical to, the native compound but differs from it in respect to certain components or side chains. Analogs may be synthetic or from a different evolutionary origin and may have a similar or opposite metabolic activity compared to wild type. Homologs are nucleic acid sequences or amino acid sequences of a particular gene that are derived from different species.

[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] Derivatives and analogs may be full length or other than full length, if the derivative or analog contains a modified nucleic acid or amino acid, as described below. 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 aforementioned 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.

[0051] 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 encode 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 1-46, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.

[0052] 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 bonafide 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.

[0053] 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 1-46; or an anti-sense strand nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1-46; or of a naturally occurring mutant of SEQ ID NO:2n−1, wherein n is an integer between 1-46.

[0054] 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 further comprises a label group attached thereto, e.g. the label group 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.

[0055] “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 1-46, 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.

NOVX Nucleic Acid and Polypeptide Variants

[0056] 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 1-46, 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 1-46. 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 1-46.

[0057] In addition to the human NOVX nucleotide sequences of SEQ ID NO:2n−1, wherein n is an integer between 1-46, 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.

[0058] Moreover, nucleic acid molecules encoding NOVX proteins from other species, and thus that have a nucleotide sequence that differs from any one of the human SEQ ID NO:2n−1, wherein n is an integer between 1-46, 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.

[0059] 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 1-46. 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 60% homologous to each other typically remain hybridized to each other.

[0060] 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.

[0061] 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.

[0062] 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 any one of the sequences of SEQ ID NO:2n−1, wherein n is an integer between 1-46, 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).

[0063] 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 1-46, 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.

[0064] 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 1-46, 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/volt) 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.

Conservative Mutations

[0065] 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 1-46, thereby leading to changes in the amino acid sequences of the encoded NOVX proteins, without altering the functional ability of said NOVX proteins. 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 1-46. 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 particularly non-amenable to alteration. Amino acids for which conservative substitutions can be made are well-known within the art.

[0066] 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 any one of SEQ ID NO:2n−1, wherein n is an integer between 1-46, 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 45% homologous to the amino acid sequences of SEQ ID NO:2n, wherein n is an integer between 1-46. 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 1-46; more preferably at least about 70% homologous to SEQ ID NO:2n, wherein n is an integer between 1-46; still more preferably at least about 80% homologous to SEQ ID NO:2n, wherein n is an integer between 1-46; even more preferably at least about 90% homologous to SEQ ID NO:2n, wherein n is an integer between 1-46; and most preferably at least about 95% homologous to SEQ ID NO:2n, wherein n is an integer between 1-46.

[0067] An isolated nucleic acid molecule encoding a NOVX protein homologous to the protein of SEQ ID NO:2n, wherein n is an integer between 1-46, 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 1-46, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.

[0068] Mutations can be introduced into any of SEQ ID NO:2n−1, wherein n is an integer between 1-46, 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 any one of SEQ ID NO:2n−1, wherein n is an integer between 1-46, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.

[0069] 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 arc 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.

[0070] 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).

[0071] 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).

Antisense Nucleic Acids

[0072] 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 1-46, 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 1-46, or antisense nucleic acids complementary to a NOVX nucleic acid sequence of SEQ ID NO:2n−1, wherein n is an integer between 1-46, are additionally provided.

[0073] 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′ untranslatcd regions).

[0074] 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).

[0075] 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-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-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-diaminopurine. 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).

[0076] 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.

[0077] 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.

Ribozymes and PNA Moieties

[0078] Nucleic acid modifications include, by way of non-limiting example, modified bases, and nucleic acids whose sugar phosphate backbones arc 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.

[0079] 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., any one of SEQ ID NO:2n−1, wherein n is an integer between 1-46). 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.

[0080] 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.

[0081] 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.

[0082] 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).

[0083] 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.

[0084] 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. Bio Techniques 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.

NOVX Polypeptides

[0085] 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 1-46. 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 1-46, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.

[0086] 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.

[0087] 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.

[0088] 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.

[0089] 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.

[0090] 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 1-46) 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.

[0091] 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.

[0092] In an embodiment, the NOVX protein has an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1-46. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO:2n, wherein n is an integer between 1-46, and retains the functional activity of the protein of SEQ ID NO:2n, wherein n is an integer between 1-46, 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 1-46, and retains the functional activity of the NOVX proteins of SEQ ID NO:2n, wherein n is an integer between 1-46.

Determining Homology Between Two or More Sequences

[0093] 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”).

[0094] 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 1-46.

[0095] 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 (e.g., 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.

Chimeric and Fusion Proteins

[0096] 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 1-46, 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.

[0097] 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.

[0098] 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.

[0099] 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.

[0100] 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.

NOVX Agonists and Antagonists

[0101] 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.

[0102] 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.

Polypeptide Libraries

[0103] 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.

[0104] 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.

NOVX Antibodies

[0105] 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.

[0106] 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 1-46, 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.

[0107] 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, 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.

[0108] 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.

[0109] 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.

[0110] 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.

Polyclonal Antibodies

[0111] 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 trypsin 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).

[0112] 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, for example, by D. Wilkinson (The Scientist, published by The Scientist, Inc., Philadelphia Pa., Vol. 14, No. 8 (Apr. 17, 2000), pp. 25-28).

Monoclonal Antibodies

[0113] 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.

[0114] 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.

[0115] 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.

[0116] 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].

[0117] 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.

[0118] 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.

[0119] 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.

[0120] 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.

Humanized Antibodies

[0121] 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)).

Human Antibodies

[0122] 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).

[0123] 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)).

[0124] 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.

[0125] 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.

[0126] 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.

[0127] 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.

Fab Fragments and Single Chain Antibodies

[0128] 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.

Bispecific Antibodies

[0129] 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.

[0130] 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).

[0131] 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).

[0132] 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.

[0133] 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.

[0134] 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.

[0135] 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).

[0136] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).

[0137] 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).

Heteroconjugate Antibodies

[0138] 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.

Effector Function Engineering

[0139] 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).

Immunoconjugates

[0140] 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).

[0141] 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.

[0142] Conjugates of the antibody and cytotoxic agent are made using a variety of bifunctional protein-coupling agents such as N-succinimidyl-3-(2-pyridyidithiol) 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), diisocyanates (such as tolyene 2,6-diisocyanate), 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.

[0143] 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.

Immunoliposomes

[0144] 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.

[0145] 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).

Diagnostic Applications of Antibodies Directed Against the Proteins of the Invention

[0146] Antibodies directed against a protein of the invention may be used in methods known within the art relating to the localization and/or quantitation of the protein (e.g., for use in measuring levels of the protein within appropriate physiological samples, for use in diagnostic methods, for use in imaging the protein, and the like). In a given embodiment, antibodies against the proteins, or derivatives, fragments, analogs or homologs thereof, that contain the antigen binding domain, are utilized as pharmacologically-active compounds (see below).

[0147] An antibody specific for a protein of the invention can be used to isolate the protein by standard techniques, such as immunoaffinity chromatography or immunoprecipitation. Such an antibody can facilitate the purification of the natural protein antigen from cells and of recombinantly produced antigen expressed in host cells. Moreover, such an antibody can be used to detect the antigenic protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the antigenic protein. Antibodies directed against the 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, P-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.

Antibody Therapeutics

[0148] 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.

[0149] 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.

[0150] 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.

Pharmaceutical Compositions of Antibodies

[0151] 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.

[0152] 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.

[0153] 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.

[0154] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.

[0155] 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 over 100 days, certain hydrogels release proteins for shorter time periods.

ELISA Assay

[0156] 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.

NOVX Recombinant Expression Vectors and Host Cells

[0157] 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.

[0158] 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).

[0159] 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.).

[0160] 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.

[0161] 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.

[0162] Examples of suitable inducible non-fusion E. coli expression vectors include pTrc (Amrann et al., (1988) 4Gene 69:301-315) and pET lid (Studieret al., GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 60-89).

[0163] 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.

[0164] 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.).

[0165] 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).

[0166] 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.

[0167] 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. Nail. 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).

[0168] 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.

[0169] 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.

[0170] 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.

[0171] 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.

[0172] 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).

[0173] 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.

Transgenic NOVX Animals

[0174] 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.

[0175] 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 1-46, 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.

[0176] 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 1-46), 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 1-46, 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).

[0177] 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.

[0178] 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.

[0179] 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.

[0180] 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.

Pharmaceutical Compositions

[0181] 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.

[0182] 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.

[0183] 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.

[0184] 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.

[0185] 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.

[0186] 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.

[0187] 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.

[0188] 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.

[0189] 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.

[0190] 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.

[0191] 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.

[0192] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

Screening and Detection Methods

[0193] 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.

[0194] The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.

Screening Assays

[0195] 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.

[0196] 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.

[0197] 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.

[0198] 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.

[0199] 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.).

[0200] 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.

[0201] 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.

[0202] 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.

[0203] 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.

[0204] 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.

[0205] 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.

[0206] 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).

[0207] 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.

[0208] 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.

[0209] 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.

[0210] 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.

[0211] 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-binding 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.

[0212] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.

Detection Assays

[0213] 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.

Chromosome Mapping

[0214] 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 1-46, 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.

[0215] 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.

[0216] 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 translocations and deletions.

[0217] 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.

[0218] 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).

[0219] 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.

[0220] 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.

[0221] 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.

Tissue Typing

[0222] 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).

[0223] 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.

[0224] 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).

[0225] 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 1-46, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.

Predictive Medicine

[0226] 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.

[0227] 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.)

[0228] 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.

[0229] These and other agents arc described in further detail in the following sections.

Diagnostic Assays

[0230] 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 1-46, 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.

[0231] 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.

[0232] 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.

[0233] 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.

[0234] 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.

Prognostic Assays

[0235] 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.

[0236] 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).

[0237] 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.

[0238] 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.

[0239] 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. Bio Technology 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.

[0240] 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.

[0241] 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.

[0242] 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. Nail. 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).

[0243] 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.

[0244] 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.

[0245] 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.

[0246] 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.

[0247] 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.

[0248] 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.

[0249] 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.

[0250] 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.

Pharmacogenomics

[0251] 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 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.) 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.

[0252] 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.

[0253] 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.

[0254] 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.

Monitoring of Effects During Clinical Trials

[0255] 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.

[0256] 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.

[0257] 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.

Methods of Treatment

[0258] 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 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, transplantation, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, 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 Ostoeodystrophy, and other diseases, disorders and conditions of the like.

[0259] These methods of treatment will be discussed more fully, below.

Disease and Disorders

[0260] 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.

[0261] 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.

[0262] 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).

Prophylactic Methods

[0263] 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.

Therapeutic Methods

[0264] 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.

[0265] Stimulation of NOVX activity is desirable in situations in which NOVX is abnormally downregulated and/or in which increased NOVX activity has 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).

Determination of the Biological Effect of the Therapeutic

[0266] 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.

[0267] 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.

Prophylactic and Therapeutic Uses of the Compositions of the Invention

[0268] The NOVX nucleic acids and proteins of the invention are useful in potential prophylactic and therapeutic applications implicated in a variety of disorders including, but not limited to: metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, 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.

[0269] 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: metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, hematopoietic disorders, and the various dyslipidemias.

[0270] 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.

EXAMPLES

Example A

Polynucleotide and Polypeptide Sequences, and Homology Data

Example 1

[0271] 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          2813 bp
NOV 1a,           TCTCGTGTATGGCGTGGTTAAGGTTGCAGCCTCTCACCTCTGCCTTCCTCCATTTTGG
CG56258-01 DNA    GCTGGTTACCTTTGTGCTCTTCCTGAATGGTCTTCGAGCAGAGGCTGGTGGCTCAGGG
Sequence          GACGTGCCAAGCACAGGGCAGAACAATGAGTCCTGTTCAGGGTCATCGGACTGCAAGG
                  AGGGTGTCATCCTGCCAATCTGGTACCCGGAGAACCCTTCCCTTGGGGACAAGATTGC
                  CAGGGTCATTGTCTATTTTGTGGCCCTGATATACATGTTCCTTGGGGTGTCCATCATT
                  GCTGACCGCTTCATGGCATCTATTGAAGTCATCACCTCTCAAGAGAGGGAGGTGACAA
                  TTAAGAAACCCAATGGAGAAACCAGCACAACCACTATTCGGGTCTGGAATGAAACTGT
                  CTCCAACCTGACCCTTATGGCCCTGGGTTCCTCTGCTCCTGAGATACTCCTCTCTTTA
                  ATTGAGGTGTGTGGTCATGGGTTCATTGCTGGTGATCTGGGACCTTCTACCATTGTAG
                  GGAGTGCAGCCTTCAACATGTTCATCATCATTGGCATCTGTGTCTACGTGATCCCAGA
                  CGGAGAGACTCGCAACATCAAGCATCTACGAGTCTTCTTCATCACCGCTGCTTGGAGT
                  ATCTTTGCCTACATCTGGCTCTATATGATTCTGGCAGTCTTCTCCCCTGGTGTGGTCC
                  AGGTTTGGGAAGGCCTCCTCACTCTCTTCTTCTTTCCAGTGTGTGTCCTTCTGGCCTG
                  GGTGGCAGATAAACGACTGCTCTTCTACAAATACATGCACAAAAAGTACCGCACAGAC
                  AAACACCGAGGAATTATCATAGAGACAGAGGGTGACCACCCTAAGGGCATTGAGATGG
                  ATGGGAAAATGATGAATTCCCATTTTCTAGATGGGAACCTGGTGCCCCTGGAAGGGAA
                  GGAAGTGGATGAGTCCCGCAGAGAGATGATCCGGATTCTCAAGGATCTGAAGCAAAAA
                  CACCCAGAGAAGGACTTAGATCAGCTGGTGGAGATCGCCAATTACTATGCTCTTTCCC
                  ACCAACAGAAGAGCCGTGCCTTCTACCGTATCCAAGCCACTCGTATGATGACTGGTGC
                  AGGCAATATCCTCAAGAAACATGCAGCAGAACAAGCCAAGAAGGCCTCCAGCATGAGC
                  GAGGTGCACACCGATGAGCCTGAGGACTTTATTTCCAAGGTCTTCTTTGACCCATGTT
                  CTTACCAGTGCCTGGAGAACTGTGGGGCTGTACTCCTGACAGTGGTGAGGAAAGGGGG
                  AGACATGTCAAAGACCATGTATGTGGACTACAAAACAGAGGATGGTTCTGCCAATGCA
                  GGGGCTGACTATGAGTTCACACAGGGCACGGTGGTTCTGAAGCCAGGAGAGACCCAGA
                  AGGAGTTCTCCGTGGGCATAATTGATGACGACATTTTTGAGGAGGATGAACACTTCTT
                  TGTAAGGTTGAGCAATGTCCGCATAGAGGAGGAGCAGCCAGAGGAGGGGATGCCTCCA
                  GCAATATTCAACAGTCTTCCCTTGCCTCGGGCTGTCCTAGCCTCCCCTTGTGTGGCCA
                  CAGTTACCATCTTGGATGATGACCATGCAGGCATCTTCACTTTTGAATGTGATACTAT
                  TCATGTCAGTGAGAGTATTGGTGTTATGGAGGTCAAGGTTCTGCGGACATCAGGTGCC
                  CGGGGTACAGTCATCGTCCCCTTTAGGACAGTAGAAGGGACAGCCAAGGGTGGCGGTG
                  AGGACTTTGAAGACACATATGGGGAGTTGGAATTCAAGAATGATGAAACTGTGAAAAC
                  TCTTCAGGTGAAGATAGTTGATGACGAGGAATATGAGAAAAAGGATAATTTCTTCATT
                  GAGCTGGGCCAGCCCCAGTGGCTTAAGCGAGGGATTTCAGCTCTGCTACTCAATCAAG
                  GGGATGGGGACAGGAAGCTAACAGCCGAGGAGGAGGAGGCTCGGAGGATAGCAGAGAT
                  GGGCAAGCCAGTTCTTGGGGAGAACTGCCGGCTGGAGGTCATCATCGAGGAGTCATAT
                  GATTTTAAGAACACGGTGGATAAACTCATCAAGAAAACGAACTTGGCCTTGGTAATTG
                  GGACCCATTCATGGAGGGAGCAGTTTTTAGAGGCAATTACGGTGAGCGCAGGGGACGA
                  GGAGGAGGAGGAGGACGGGTCCCGGGAGGAGCGGCTGCCGTCGTGCTTTGACTACGTG
                  ATGCACTTCCTGACGGTGTTCTGGAAGGTCCTCTTCGCCTGTGTGCCCCCCACCGAGT
                  ACTGCCACGGCTGGGCCTGCTTTGGTGTCTCCATCCTGGTCATCGGCCTGCTCACCGC
                  CCTCATTGGGGACCTCGCCTCCCACTTCGGCTGCACCGTTGGCCTCAAGGACTCTGTC
                  AATGCTGTTGTCTTCGTTGCCCTGGGCACCTCCATCCCTGACACGTTCGCCAGCAAGG
                  TGGCGGCGCTGCAGGACCAGTGCGCCGACGCGTCCATCGGCAACGTGACCCGCTCCAA
                  CGCGGTGAACGTGTTCCTTGGCCTGGGCGTCGCCTGGTCTGTGGCCGCCGTGTACTGG
                  GCGGTGCAGGGCCGCCCCTTCGAGGTGCGCACTGGCACGCTGGCCTTCTCCGTCACGC
                  TCTTCACCGTCTTCGCCTTCGTGGGCATTGCCGTGCTGCTGTACCGGCGCCGGCCGCA
                  CATCGGCGGCGAGCTGGGCGGCCCGCGCGGACCCAAGCTCGCCACCACCGCGCTCTTC
                  CTGGGCCTCTGGCTCCTGTACATCCTCTTCGCCAGCCTGGAGGCGTACTGCCACATCC
                  GGGGCTTCTAGGGCCTCGCGCAGAGACTC
                  ORF Start: ATG at 9  ORF Stop: TAG at 2793
                  SEQ ID NO:2          928 aa MW at 102900.1 kD
NOV1a,            MAWLRLQPLTSAFLHFGLVTFVLFLNGLRAEAGGSGDVPSTGQNNESCSGSSDCKEGV
CG56258-01        ILPIWYPENPSLGDKIARVIVYFVALIYMFLGVSIIADRFMASIEVITSQEREVTIKK
Protein Sequence  PNGETSTTTIRVWNETVSNLTLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSA
                  AFNMFIIIGICVYVIPDGETRKIKHLRVFFITAAWSIFAYIWLYMILAVFSPCVVQVW
                  EGLLTLFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRGIIIETEGDHPKGIEMDGK
                  MMNSHFLDGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMANYYALSHQQ
                  KSRAFYRIQATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQ
                  CLENCGAVLLTVVRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTVVLKPGETQKEF
                  SVGIIDDDIFEEDEHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVT
                  ILDDDHAGIFTFECDTIHVSESIGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDF
                  EDTYGELEFKNDETVKTLQVKIVDDEEYEKKDNFFIELGQPQWLKRGISALLLNQGDG
                  DRKLTAEEEEARRIAEMGKPVLGENCRLEVIIEESYDFKNTVDKLIKKTNLALVIGTH
                  SWREQFLEAITVSAGDEEEEEDGSREERLPSCFDYVMHFLTVFWKVLFACVPPTEYCH
                  GWACFGVSILVIGLLTALIGDLASHFGCTVGLKDSVNAVVFVALGTSIPDTFASKVAA
                  LQDQCADASIGNVTGSNAVNVFLGLGVAWSVAAVYWAVQGRPFEVRTGTLAFSVTLFT
                  VFAFVGIAVLLYRRRPHIGGELGGPRGPKLATTALFLGLWLLYILFASLEAYCHIRGF
                  SEQ ID NO:3          2840 bp
NOV 1b,           GTCTCTGGCCTATCAGGAGGACAACTGGTGCTGCAATAGAAGCCAGTGGCTAAGTCTC
CG56258-02 DNA    GTGTATGGCGTGGTTAAGGTTGCACCCTCTCACCTCTGCCTTCCTCCATTTTGGGCTG
Sequence          GTTACCTTTGTGCTCTTCCTGAATGGTCTTCGAGCAGAGGCTGGTGGCTCAGGGGACG
                  TGCCAAGCACAGGGCAGAACAATGAGTCCTGTTCAGGGTCATCGGACTGCAAGGAGGG
                  TGTCATCCTGCCAATCTGGTACCCGGAGAACCCTTCCCTTGGGGACAAGATTGCCAGG
                  GTCATTGTCTATTTTGTGGCCCTGATATACATGTTCCTTGGGGTGTCCATCATTGCTG
                  ACCGCTTCATGGCATCTATTGAAGTCATCACCTCTCAAGAGAGGGAGGTGACAATTAA
                  GAAACCCAATGGAGAAACCAGCACAACCACTATTCGGGTCTGGAATGAAACTGTCTCC
                  AACCTGACCCTTATGGCCCTGGGTTCCTCTGCTCCTGAGATACTCCTCTCTTTAATTG
                  AGGTGTGTGGTCATGGGTTCATTGCTGGTGATCTGGGACCTTCTACCATTGTAGGGAG
                  TGCAGCCTTCAACATGTTCATCATCATTGGCATCTGTGTCTACGTGATCCCAGACGGA
                  GAGACTCGCAAGATCAAGCATCTACGAGTCTTCTTCATCACCGCTGCTTGGAGTATCT
                  TTGCCTACATCTGGCTCTATATGATTCTGGCAGTCTTCTCCCCTGGTGTGGTCCAGGT
                  TTGGGAAGGCCTCCTCACTCTCTTCTTCTTTCCAGTGTGTGTCCTTCTGGCCTGGGTG
                  GCAGATAAACGACTGCTCTTCTACAAATACATGCACAAAAAGTACCGCACAGACAAAC
                  ACCGAGGAATTATCATAGAGACAGAGGGTGACCACCCTAAGGGCATTGAGATGGATGG
                  GAAAATGATGAATTCCCATTTTCTAGATGGGAACCTGGTGCCCCTGGAAGGGAAGGAA
                  GTGGATGAGTCCCGCAGAGAGATGATCCGGATTCTCAAGGATCTGAAGCAAAAACACC
                  CAGAGAAGGACTTAGATCAGCTGGTGGAGATGGCCAATTACTATGCTCTTTCCCACCA
                  ACAGAAGAGCCGTGCCTTCTACCGTATCCAAGCCACTCGTATGATGACTGGTGCAGGC
                  AATATCCTGAAGAAACATGCAGCAGAACAAGCCAAGAAGGCCTCCAGCATGAGCGAGG
                  TGCACACCGATGAGCCTGAGGACTTTATTTCCAAGGTCTTCTTTGACCCATGTTCTTA
                  CCAGTGCCTGGAGAACTGTGGGGCTGTACTCCTGACAGTGGTGAGGAAAGGGGGAGAC
                  ATGTCAAAGACCATGTATGTGGACTACAAAACAGAGGATGGTTCTGCCAATGCACGGG
                  CTGACTATGAGTTCACAGAGGGCACGGTGGTTCTGAAGCCAGGAGAGACCCAGAAGGA
                  GTTCTCCGTGGGCATAATTGATGACGACATTTTTGAGGAGGATGAACACTTCTTTGTA
                  AGGTTGAGCAATGTCCGCATAGAGGAGGAGCAGCCAGAGGAGGGGATGCCTCCAGCAA
                  TATTCAACAGTCTTCCCTTGCCTCGGGCTGTCCTAGCCTCCCCTTGTGTGGCCACAGT
                  TACCATCTTGGATGATGACCATGCACGCATCTTCACTTTTGAATGTGATACTATTCAT
                  GTCAGTGAGAGTATTGGTGTTATGGAGGTCAAGGTTCTGCGGACATCAGGTGCCCGGG
                  GTACAGTCATCGTCCCCTTTAGGACAGTAGAAGGGACAGCCAAGGGTGGCGGTGAGGA
                  CTTTGAAGACACATATGGGGAGTTGGAATTCAAGAATGATCAAACTGTCAAAACAATT
                  CACATCAAGGTAATTGATGATGAGGCATATGAGAAAAACAAGAATTACTTCATTGAGA
                  TGATGGGCCCCCGCATGGTGGATATGAGTTTTCAGAAAGCGCTCCTGTTATCTCCAGA
                  CAGGAAGCTGACTATGCAAGAAGAGGAGGCCAAGAGGATAGCAGAGATGGGAAACCCA
                  GTATTGGGTGAACACCCCAAACTAGAAGTCATCATTGAAGAGTCCTATGAGTTCAAGA
                  CTACGGTGGACAAACTGATCAAGAAGACAAACCTGGCCTTGGTTGTGGGGACCCATTC
                  CTGGAGGGACCAGTTCATGGAGGCCATCACCGTCAGTGCAGCAGGGGATGAGGATGAG
                  GATGAATCCGGGGAGGAGAGGCTGCCCTCCTGCTTTGACTACGTCATGCACTTCCTGA
                  CTGTCTTCTGGAAGGTGCTGTTTGCCTGTGTGCCCCCCACAGAGTACTGCCACGGCTG
                  GGCCTGCTTCGCCGTCTCCATCCTCATCATTGGCATGCTCACCGCCATCATTGGGGAC
                  CTGGCCTCGCACTTCGGCTGCACCATTGGTCTCAAAGATTCAGTCACAGCTGTTGTTT
                  TCGTGGCATTTGGCACCTCTGTCCCAGATACGTTTGCCAGCAAAGCTGCTGCCCTCCA
                  GGATGTATATGCAGACGCCTCCATTGGCAACGTGACGGGCAGCAACGCCGTCAATGTC
                  TTCCTGGGCATCGGCCTGGCCTGGTCCGTGGCCGCCATCTACTGGGCTCTGCAGGGAC
                  AGGAGTTCCACGTGTCGGCCGGCACACTGGCCTTCTCCGTCACCCTCTTCACCATCTT
                  TGCATTTGTCTGCATCAGCGTGCTCTTGTACCGAAGGCGGCCGCACCTGGGAGGGGAG
                  CTTGGTGGCCCCCGTGGCTGCAAGCTCGCCACAACATGGCTCTTTGTGAGCCTGTGGC
                  TCCTCTACATACTCTTTGCCACACTAGAGGCCTATTGCTACATCAAGGGGTTCTAA
                  ORF Start: ATG at 63 ORF Stop: TAA at 2838
                  SEQ ID NO:4          925 aa MW at 102802.3 kD
NOV1b,            MAWLRLQPLTSAFLHFGLVTFVLFLNGLRAEAGGSGDVPSTGQNNESCSGSSDCKEGV
CG56258-02        ILPIWYPENPSLGDKIARVIVYFVALIYMFLGVSIIADRFMASIEVITSQEREVTIKK
Protein Sequence  PNGETSTTTIRVWNETVSNLTLMALGSSAPEILLSLIEVCGHGFIAGDLGPSTIVGSA
                  AFNMFIIIGICVYVIPDGETRKIKHLRVFFITAAWSIFAYIWLYMILAVFSPGVVQVW
                  EGLLTLFFFPVCVLLAWVADKRLLFYKYMHKKYRTDKHRGIIIETEGDHPKGIEMDGK
                  MMNSHFLDGNLVPLEGKEVDESRREMIRILKDLKQKHPEKDLDQLVEMANYYALSHQQ
                  KSRAFYRIQATRMMTGAGNILKKHAAEQAKKASSMSEVHTDEPEDFISKVFFDPCSYQ
                  CLENCGAVLLTVVRKGGDMSKTMYVDYKTEDGSANAGADYEFTEGTVVLKPGETQKEF
                  SVGIIDDDIFEEDEHFFVRLSNVRIEEEQPEEGMPPAIFNSLPLPRAVLASPCVATVT
                  ILDDDHAGIFTFECDTIHVSESIGVMEVKVLRTSGARGTVIVPFRTVEGTAKGGGEDF
                  EDTYGELEFKNDETVKTIHIKVIDDEAYEKNKNYFIEMMGPRMVDMSFQKALLLSPDR
                  KLTMEEEEAKRIAEMGKPVLGEHPKLEVIIEESYEFKTTVDKLIKKTNLALVVGTHSW
                  RDQFMEAITVSAAGDEDEDESGEERLPSCFDYVMHFLTVFWKVLFACVPPTEYCHGWA
                  CFAVSILIIGMLTAIIGDLASHFGCTIGLKDSVTAVVFVAFGTSVPDTFASKAAALQD
                  VYADASIGNVTFSNAVNVFLGIGLAWSVAAIYWALQGQEFHVSAGTLAFSVTLFTIFA
                  FVCISVLLYRRRPHLGGELGGPRGCKLATTWLFVSLWLLYILFATLEAYCYIKGF
                  SEQ ID NO:5          2685 bp
NOV1c,            GGATCCGAGGCTGGTGGCTCAGGGGACGTGCCAAGCACAGGGCAGAACAATGAGTCCT
248057963 DNA     GTTCAGGGTCATCGGACTGCAAGGAGGGTGTCATCCTGCCAATCTGGTACCCGGAGAA
Sequence          CCCTTCCCTTGGGGACAAGATTGCCAGGGTCATTGTCTATTTTGTGGCCCTGATATAC
                  ATGTTCCTTGGGGTGTCCATCATTGCTGACCGCTTCATGGCATCTATTGAAGTCATCA
                  CCTCTCAACAGAGGGAGGTGACAATTAAGAAACCCAATGGAGAAACCAGCACAACCAC
                  TATTCGGGTCTGGAATGAAACTGTCTCCAACCTGACCCTTATGGCCCTGGGTTCCTCT
                  GCTCCTGAGATACTCCTCTCTTTAATTGAGGTGTGTGGTCATGGGTTCATTGCTGGTG
                  ATCTGGGACCTTCTACCATTGTAGGGAGTGCAGCCTTCAACATGTTCATCATCATTGG
                  CATCTGTGTCTACGTGATCCCAGACGGAGAGACTCGCAAGATCAAACATCTACGAGTC
                  TTCTTCATCACCGCTGCTTGGAGTATCTTTGCCTACATCTGGCTCTATATGATTCTGG
                  CAGTCTTCTCCCCTGGTGTGGTCCAGGTTTGGGAAGGCCTCCTCACTCTCTTCTTCTT
                  TCCAGTGTGTGTCCTTCTGGCCTGGGTGGCAGATAAACGACTGCTCTTCTACAAATAC
                  ATGCACAAAAAGTACCGCACAGACAAACACCGAGGAATTATCATAGAGACAGAGGGTG
                  ACCACCCTAAGGGCATTGAGATGGATGGGAAAATGATGAATTCCCATTTTCTAGATGG
                  GAACCTGGTGCCCCTGGAAGGGAAGGAAGTGGATGAGTCCCGCAGAGAGATGATCCGG
                  ATTCTCAAGGATCTGAAGCAAAAACACCCAGAGAAGCACTTAGATCAGCTGGTGGAGA
                  TGGCCAATTACTATGCTCTTTCCCACCAACAGAAGAGCCGCGCCTTCTACCGTATCCA
                  AGCCACTCGTATGATGACTGGTGCAGGCAATATCCTGAAGAAACATGCAGCAGAACAA
                  GCCAAGAAGGCCTCCAGCATGAGCGAGGTGCACACCGATGAGCCTGAGGACTTTATTT
                  CCAAGGTCTTCTTTGACCCATGTTCTTACCAGTGCCTGGAGAACTGTGGGGCTGTACT
                  CCTGACAGTGGTGAGGAAAGGGGGAGACATGTCAAAGACCATGTATGTGGACTACAAA
                  ACAGAGGATGGTTCTGCCAATGCAGGGGCTGACTATGAGTTCACAGAGGGCACGGTGC
                  TTCTGAAGCCAGGAGAGACCCAGAAGGAGTTCTCCGTGGGCATAATTGATGACGACAT
                  TTTTGAGGAGGATGAACACTTCTTTGTAAGGTTGAGCAATGTCCGCATAGAGGAGGAG
                  CAGCCAGAGGAGGGGATGCCTCCAGCAATATTCAACAGTCTTCCCTTGCCTCGGGCTG
                  TCCTAGCCTCCCCTTGTGTGGCCACAGTTACCATCTTGGATGATGACCATGCAGGCAT
                  CTTCACTTTTGAATGTGATACTATTCATGTCAGTGAGAGTATTGGTGTTATGGACGTC
                  AAGGTTCTGCGGACATCAGGTGCCCGGGGTACAGTCATCGTCCCCTTTAGGACAGTAG
                  AAGGGACAGCCAAGGGTGGCGGTGAGGACTTTGAAGACACATATGGGGAGTTGGAATT
                  CAAGAATGATGAAACTGTGAAAACCATAAGGGTTAAAATAGTAGATGAGGAGGAATAC
                  GAAAGGCAAGAGAATTTCTTCATTGCCCTTGGTGAACCGAAATGGATGGAACGTGGAA
                  TATCAGATGTGACAGACAGGAAGCTGACTATGGAAGAAGAGGAGGCCAAGAGGATAGC
                  AGAGATGGGAAAGCCAGTATTGGGTGAACACCCCAAACTAGAAGTCATCATTGAAGAG
                  TCCTATGAGTTCAAGACTACGGTGGACAAACTGATCAAGAAGACAAACCTGGCCTTGG
                  TTGTGGGGACCCATTCCTGGAGGGACCAGTTCATGGAGGCCATCACCGTCAGTGCAGC
                  AGGGGATGAGOATGAGGATGAATCCGGGGAGGAGAGGCTGCCCTCCTGCTTTGACTAC
                  GTCATGCACTTCCTGACTGTCTTCTGGAAGGTGCTGTTTGCCTGTGTGCCCCCCACAG
                  AGTACTGCCACGGCTGGGCCTGCTTCGCCGTCTCCATCCTCATCATTGGCATGCTCAC
                  CGCCATCATTGGGGACCTGGCCTCGCACTTCGGCTGCACCATTGGTCTCAAAGATTCA
                  GTCACAGCTGTTGTTTTCGTGGCATTTGGCACCTCTGTCCCAGATACGTTTGCCAGCA
                  AAGCTGCTGCCCTCCAGGATGTATATGCAGACGCCTCCATTGGCAACGTGACGGGCAG
                  CAACGCCGTCAATGTCTTCCTGGGCATCGGCCTGGCCTGGTCCGTGGCCGCCATCTAC
                  TGGGCTCTGCAGGGACAGGAGTTCCACGTGTCGGCCGGCACACTGGCCTTCTCCGTCA
                  CCCTCTTCACCATCTTTGCATTTGTCTGCATCAGCGTGCTCTTGTACCGAAGGCGGCC
                  GCACCTGGGAGGGGAGCTTGGTGGCCCCCGTGGCTGCAAGCTCGCCACAACATGGCTC
                  TTTGTGAGCCTGTGGCTCCTCTACATACTCTTTGCCACACTAGAGGCCTATTGCTACA
                  TCAAGGGGTTCCTCGAG
                  ORF Start: at 1      ORF Stop: end of Sequence
                  SEQ ID NO:6          895 aa MW at 99385.0 kD
NOV1c,            GSEAGGSGDVPSTGQNNESCSGSSDCKEGVILPIWYPENPSLGDKIARVIVYFVALIY
248057963 Protein MFLGVSIIADRFMASIEVITSQEREVTIKKPNGETSTTTIRVWNETVSNLTLMALGSS
Sequence          APEILLSLIEVCGHGFIAGDLGPSTIVGSAAFNMFIIIGICVYVIPDGETRKIKHLRV
                  FFITAAWSIFAYIWLYMILAVFSPGVVQVWEGLLTLFFFPVCVLLAWVADKRLLFYKY
                  MHKKYRTDKHRGIIIETEGDHPKGIEMDGKMMNSHFLDGNLVPLEGKEVDESRREMIR
                  ILKDLKQKHPEKDLDQLVEMANYYALSHQQKSRAFYRIQATRMMTGAGNILKKHAAEQ
                  AKKASSMSEVHTDEPEDFISKVFFDPCSYQCLENCGAVLLTVVRKGGDMSKTMYVDYK
                  TEDGSANAGADYEFTEGTVVLKPGETQKEFSVGIIDDDIFEEDEHFFVRLSNVRIEEE
                  QPEEGMPPAIFNSLPLPRAVLASPCVATVTILDDDHAGIFTFECDTIHVSESIGVMEV
                  KVLRTSGARGTVIVPFRTVEGTAKGGGEDFEDTYGELEFKNDETVKTIRVKIVDEEEY
                  ERQENFFIALGEPKWMERGISDVTDRKLTMEEEEAKRIAEMGKPVLGEHPKLEVIIEE
                  SYEFKTTVDKLIKKTNLALVVGTHSWRDQFMEAITVSAAGDEDEDESGEERLPSCFDY
                  VMHFLTVFWKVLFACVPPTEYCHGWACFAVSILIIGMLTAIIGDLASHFGCTIGLKDS
                  VTAVVFVAFGTSVPDTFASKAAALQDVYADASIGNVTGSNAVNVFLGIGLAWSVAAIY
                  WALQGQEFHVSAGTLAFSVTLFTIFAFVCISVLLYRRRPHLGGELGGPRGCKLATTWL
                  FVSLWLLYILFATLEAYCYIKGFLE

[0272] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 1B.

TABLE lB
Comparison of NOV1a against NOV1b and NOV1c.
	NOV1a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV1b	1 . . . 928	833/929 (89%)
	1 . . . 925	866/929 (92%)
NOV1c	30 . . . 928	808/899 (89%)
	2 . . . 893	844/899 (93%)

[0273] Further analysis of the NOV1a protein yielded the following properties shown in Table 1C.

TABLE 1C
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 31 and 32
analysis:

[0274] 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 1D.

TABLE 1D
Geneseq Results for NOV1a
		NOV1a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM47745	Human natrium(+)-calcium(2+)	1 . . . 928	862/929 (92%)	0.0
	exchanger form 3 protein, HNCX3 -	1 . . . 927	900/929 (96%)
	Homo sapiens, 927 aa.
	[WO200183744-A2, 08-NOV-2001]
AAB41497	Human ORFX ORF1261 polypeptide	48 . . . 928	701/890 (78%)	0.0
	sequence SEQ ID NO: 2522 - Homo	74 . . . 952	788/890 (87%)
	sapiens, 952 aa. [WO200058473-A2,
	05-OCT-2000]
AAM26102	Peptide #139 encoded by probe for	1 . . . 593	420/606 (69%)	0.0
	measuring placental gene expression -	11 . . . 608	496/606 (81%)
	Homo sapiens, 609 aa.
	[WO200157272-A2, 09-AUG-2001]
AAM13701	Peptide #135 encoded by probe for	1 . . . 593	420/606 (69%)	0.0
	measuring cervical gene expression -	11 . . . 608	496/606 (81%)
	Homo sapiens, 609 aa.
	[WO200157278-A2, 09-AUG-2001]
AAM53461	Human brain expressed single exon	1 . . . 593	420/606 (69%)	0.0
	probe encoded protein SEQ ID NO:	11 . . . 608	496/606 (81%)
	25566 - Homo sapiens, 609 aa.
	[WO200157275-A2, 09-AUG-2001]

[0275] In a BLAST search of public sequence databases, the NOV1a protein was found to have homology to the proteins shown in the BLASTP data in Table 1E.

TABLE lE
Public BLASTP Results for NOV1a
		NOV1a	Identities/
Protein		Residues/	Similarities for
Accession	Protein/	Match	the Matched	Expect
Number	Organism/Length	Residues	Portion	Value
Q96QG1	SODIUM/CALCIUM	1 . . . 928	866/929 (93%)	0.0
	EXCHANGER SCL8A3 -	1 . . . 924	903/929 (96%)
	Homo sapiens (Human),
	924 aa.
Q96QG2	SODIUM/CALCIUM	1 . . . 928	857/930 (92%)	0.0
	EXCHANGER SCL8A3 -	1 . . . 925	892/930 (95%)
	Homo sapiens (Human),
	925 aa.
P70549	Sodium/calcium	1 . . . 928	848/929 (91%)	0.0
	exchanger 3 precursor	1 . . . 927	895/929 (96%)
	(Na(+)/Ca(2+)-
	exchange protein 3) -
	Rattus norvegicus (Rat),
	927 aa.
AAL39160	SODIUM/CALCIUM	1 . . . 928	837/929 (90%)	0.0
	EXCHANGER - Mus	1 . . . 928	879/929 (94%)
	musculus (Mouse),
	928 aa.
Q9UPR5	Sodium/calcium	48 . . . 928	701/890 (78%)	0.0
	exchanger 2 precursor	43 . . . 921	788/890 (87%)
	(Na(+)/Ca(2+)-exchange
	protein 2) - Homo sapiens
	(Human), 921 aa.

[0276] PFam analysis indicates that the NOV1a protein contains the domains shown in Table 1F.

TABLE 1F
Domain Analysis of NOV1a
		Identities/
		Similarities
	NOV1a Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
Filo_VP35:	184 . . . 199	7/16 (44%)	6.1
domain 1 of 1		10/16 (62%)
Na_Ca_Ex:	110 . . . 257	35/153 (23%)	1.2e-32
domain 1 of 2		120/153 (78%)
Glycos_transf_4:	760 . . . 910	33/215 (15%)	5.7
domain 1 of 1		95/215 (44%)
Na_Ca_Ex:	764 . . . 912	55/152 (36%)	2.le-48
domain 2 of 2		130/152 (86%)

Example 2

[0277] 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:7          2277 bp
NOV2a,           CCGGCTCCCGCGCCCTCCCCGCCGGCCATGCAGCCCCGCCGCGCCCAGGCGCCCGGTG
CG59843-01 DNA   CGCAGCTGCTGCCCGCGCTGGCCCTGCTGCTGCTGCTGCTCGGAGCGGGGCCCCGAGG
Sequence         CAGCTCCCTGGCCAACCCGGTGCCCGCCGCGCCCCTGTCTGCGCCCGGGCCGTGCGCC
                 GCGCAGCCCTGCCGGAATGGGGGTGTGTGCACCTCGCGCCCTGAGCCGGACCCGCAGC
                 ACCCGGCCCCCGCCGGCGAGCCTGGCTACAGCTGCACCTGCCCCGCCGGGATCTCCGG
                 CGCCAACTGCCAGCTTGTTGCAGATCCTTGTGCCAGCAACCCTTGTCACCATGGCAAC
                 TGCAGCAGCAGCAGCAGCAGCAGCAGCGATGGCTACCTCTGCATTTGCAATGAAGGCT
                 ATGAAGGTCCCAACTGTGAACAGGCACTTCCCAGTCTCCCAGCCACTGGCTGGACCGA
                 ATCCATGGCACCCCGACAGCTTCAGCCTGTTCTTGCTACTCAGGAGCCTGACAAAATC
                 CTGCCTCGCTCTCAGGCAACGGTGACACTGCCTACCTGGCAGCCGAAAACAGGGCAGA
                 AAGTTGTAGAAATGAAATGGGATCAAGTGGAGGTGATCCCAGATATTGCCTGTGGGAA
                 TGCCAGTTCTAACAGCTCTGCGGGTGGCCGCCTGGTATCCTTTGAAGTGCCACAGAAC
                 ACCTCAGTCAAGATTCGGCAAGATGCCACTGCCTCACTGATTTTCCTCTGGAAGGTCA
                 CGGCCACAGGATTCCAACAGTGCTCCCTCATAGATGGACGAAGTGTGACCCCCCTTCA
                 GGCTTCAGGGGGACTGGTCCTCCTGGAGGAGATGCTCGCCTTGGGGAATAATCACTTT
                 ATTGGTTTTGTGAATGATTCTGTGACTAAGTCTATTGTGGCTTTGCGCTTAACTCTGG
                 TGGTGAAGGTCAGCACCTGTGTGCCGGGGGAGAGTCACGCAAATGACTTGGAGTGTTC
                 AGGAAAAGGAAAATGCACCACGAAGCCGTCAGAGGCAACTTTTTCCTGTACCTGTGAG
                 GAGCAGTACGTGGGTACTTTCTGTGAAGAATACGATGCTTGCCAGAGGAAACCTTGCC
                 AAAACAACGCGAGCTGTATTGATGCAAATGAAAAGCAAGATGGGAGCAATTTCACCTG
                 TGTTTGCCTTCCTGGTTATACTGGAGAGCTTTGCCAGTCCAAGATTGATTACTGCATC
                 CTAGACCCATGCAGAAATGGAGCAACATGCATTTCCAGTCTCAGTCGATTCACCTGCC
                 AGTGTCCAGAAGGATACTTCGGATCTGCTTGTGAAGAAAAGGTGGACCCCTGCGCCTC
                 GTCTCCGTGCCAGAACAACGCCACCTGCTATGTGGACGGGGTACACTTTACCTGCAAC
                 TGCAGCCCGGGCTTCACAGGGCCGACCTGTGCCCAGCTTATTGACTTCTGTGCCCTCA
                 GCCCCTGTGCTCATGGCACGTGCCGCAGCGTGGGCACCAGCTACAAATGCCTCTGTGA
                 TCCAGGTTACCATGCCCTCTACTGTGAGGAGGAATATAATGAGTGCCTCTCCGCTCCA
                 TGCCTGAATGCAGCCACCTGCAGGGACCTCGTTAATGGCTATGAGTGTGTGTGCCTGG
                 CAGAATACAAAGGAACACACTGTGAATTGTACAAGGATCCCTGCGCTAACGTCAGCTG
                 TCTGAACGGAGCCACCTGTGACAGCGACGGCCTGAATGGCACGTGCATCTGTGCACCC
                 GGGTTTACAGGTGAAGAGTGCGACATTGACATAAATGAATGTGACAGTAACCCCTGCC
                 ACCATGGTGGGAGCTGCCTGGACCAGCCCAATGGTTATAACTGCCACTGCCCGCATGG
                 TTGGGTGGGAGCAAACTGTGAGATCCACCTCCAATGGAAGTCCGGGCACATGGCGGAG
                 AGCCTCACCAACATGCCACGGCACTCCCTCTACATCATCATTGGAGCCCTCTGCGTGG
                 CCTTCATCCTTATGCTGATCATCCTGATCGTGGGGATTTGCCGCATCAGCCGCATTGA
                 ATACCAGGGTTCTTCCAGGCCAGCCTATGAGGAGTTCTACAACTGCCGCAGCATCGAC
                 AGCGAGTTCAGCAATGCCATTGCATCCATCCGGCATGCCAGGTTTGGAAAGAAATCCC
                 GGCCTGCAATGTATGATGTGAGCCCCATCGCCTATGAAGATTACAGTCCTGATGACAA
                 ACCCTTGGTCACACTGATTAAAACTAAAGATTTGTAATCTTTTTTTGGATTATTTTTC
                 AAAAAGATGAGATAC
                 ORF Start: ATG at 28 ORF Stop: TAA at 2239
                 SEQ ID NO:8          737 aa MW at 78473.7 kD
NOV2a,           MQPRRAQAPGAQLLPALALLLLLLGAGPRGSSLANPVPAAPLSAPGPCAAQPCRNGGV
CG59843-01       CTSRPEPDPQHPAPAGEPGYSCTCPAGISGANCQLVADPCASNPCHHGNCSSSSSSSS
Protein Sequence DGYLCICNEGYECPNCEQALPSLPATGWTESMAPRQLQPVPATQEPDKILPRSQATVT
                 LPTWQPKTGQKVVEMKWDQVEVIPDIACGNASSNSSAGGRLVSFEVPQNTSVKIRQDA
                 TASLILLWKVTATGFQQCSLIDGRSVTPLQASGGLVLLEEMLALGNNHFIGFVNDSVT

[0278] Further analysis of the NOV2a protein yielded the following properties shown in Table 2B.

TABLE 2B
Protein Sequence Properties NOV2a
PSort     0.4600 probability located in plasma membrane;
analysis: 0.1000 probability located in endoplasmic
          reticulum (membrane); 0.1000 probability
          located in endoplasmic reticulum (lumen);
          0.1000 probability located in outside
SignalP   Cleavage site between residues 35 and 36
analysis:

[0279] 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 2C.

TABLE 2C
Geneseq Results for NOV2a
		NOV2a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/	Match	the Matched	Expect
Identifier	Length [Patent #, Date]	Residues	Region	Value
AAU29042	Human PRO polypeptide sequence #	1 . . . 737	737/737 (100%)	0.0
	19 - Homo sapiens, 737 aa.	1 . . . 737	737/737 (100%)
	[WO200168848-A2, 20-SEP-2001]
AAB01313	Human PRO299 polypeptide -	1 . . . 737	737/737 (100%)	0.0
	Homo sapiens, 737 aa.	1 . . . 737	737/737 (100%)
	[WO200032776-A2, 08-JUN-2000]
AAY17822	Human PRO299 protein sequence -	1 . . . 737	737/737 (100%)	0.0
	Homo sapiens, 737 aa.	1 . . . 737	737/737 (100%)
	[WO9928462-A2, 10-JUN-1999]
AAW39257	Human membrane protein - Homo	1 . . . 737	737/737 (100%)	0.0
	sapiens, 737 aa. [JP10036395-A,	1 . . . 737	737/737 (100%)
	10-FEB-1998]
AAW39256	Human partial mature membrane	27 . . . 638	612/612 (100%)	0.0
	protein - Homo sapiens, 612 aa.	1 . . . 612	612/612 (100%)
	[JP10036395-A, 10-FEB-1998]

[0280] 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 2D.

TABLE 2D
Public BLASTP Results for NOV2a
		NOV2a	Identities/
Protein		Rcsidues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
BAB72175	TRANSMEMBRANE PROTEIN	1 . . . 737	666/737 (90%)	0.0
	BET - Mus musculus (Mouse),	1 . . . 737	694/737 (93%)
	737 aa.
AAH24766	HYPOTHETICAL 49.8 KDA	279 . . . 737	459/459 (100%)	0.0
	PROTEIN - Homo sapiens	1 . . . 459	459/459 (100%)
	(Human), 459 aa (fragment).
AAH22636	HYPOTHETICAL 42.4 KDA	349 . . . 737	371/389 (95%)	0.0
	PROTEIN - Mus musculus	1 . . . 389	382/389 (97%)
	(Mouse), 389 aa (fragment).
Q9NTF1	HYPOTHETICAL 27.8 KDA	486 . . . 737	252/252 (100%)	e−158
	PROTEIN - Homo sapiens	1 . . . 252	252/252 (100%)
	(Human), 252 aa (fragment).
Q9UDM2	WUGSC:H_NH0150O02.1	384 . . . 575	192/192 (100%)	e−123
	PROTEIN - Homo sapiens	1 . . . 192	192/192 (100%)
	(Human), 192 aa (fragment).

[0281] PFam analysis indicates that the NOV2a protein contains the domains shown in Table 2E.

TABLE 2E
Domain Analysis of NOV2a
		Identities/
	NOV2a	Similarities
	Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
EGF: domain 1 of 10	48 . . . 91	17/50 (34%)	0.038
		34/50 (68%)
EGF: domain 2 of 10	98 . . . 132	16/47 (34%)	1.5e−05
		27/47 (57%)
Vinculin: domain 1 of 1	225 . . . 248	11/29 (38%)	6.5
		17/29 (59%)
EGF: domain 3 of 10	307 . . . 347	12/51 (24%)	1.1
		28/51 (55%)
EGF: domain 4 of 10	353 . . . 389	14/47 (30%)	5.9e−07
		28/47 (60%)
EGF: domain 5 of 10	396 . . . 427	16/47 (34%)	2.8e−07
		26/47 (55%)
metalthio: domain 1 of 1	398 . . . 458	17/70 (24%)	5.7
		29/70 (41%)
EGF: domain 6 of 10	434 . . . 465	16/47 (34%)	2.2e−06
		25/47 (53%)
Keratin_B2:	343 . . . 496	39/194 (20%)	0.72
domain 1 of 1		80/194 (41%)
EGF: domain 7 of 10	472 . . . 502	15/47 (32%)	3.2e−07
		25/47 (53%)
EGE: domain 8 of 10	509 . . . 540	13/47 (28%)	2.2e−06
		23/47 (49%)
EGF: domain 9 of 10	547 . . . 578	15/47 (32%)	0.00048
		23/47 (49%)
DSL: domain 1 of 1	509 . . . 578	17/73 (23%)	3.4
		44/73 (60%)
EGF: domain 10 of 10	585 . . . 616	16/47 (34%)	2.7e−07
		27/47 (57%)
Rhabd_glycop:	638 . . . 684	9/50 (18%)	1.5
domain 1 of 1		31/50 (62%)

Example 3

[0282] 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:9          813 bp
NOV3a,           TTGGGGAGAAGATTAAAAAATGCTAGAAGCATGCCAACATATAAAATTCCAAGTCAAT
CG59845-01 DNA   GGTCAAACAGTGCACTCGCATCTCTCACATCACCCACTTGGCCCTCTTCCAAATGTAC
Sequence         TTTACTTCCTCTTCTCATCCTTTCGTTGCTGTCTCCCTTCACAGAACAATTCATAGTG
                 AATAGCTTAAAGAGGCCAATCTTGGCTCCACTGGGTGGAAAAGTTGAGCTCAGTTGCC
                 AGCTGTCTCCACCACAAAGCGCAGAACACATGGAAATACGCTGGTTCCAGAGTCACTA
                 CACACGACCTGTTTACCTGTATAAGGATGGTAAAGACCTGTATGGAGAAACTATCTCC
                 AAGTATGTGGAGCGGACAGAGCTCCTGAAAGAAGCCATTGGAGAAGGTAAAGTGACCC
                 TCAGGATCCTTAATGTCAGTGCTGATGATGACGGGCAGTACCACTGCTTCTTCAAAGA
                 CAGAAATGTCTATGAAGAGTCCATCACAGAAGTGAAGGTCTCAGATAAACTGTTTCCA
                 TGGAATTCTATCTGGATACTGATTCTGGTTGCAATCTTGGCTGTTCTGCTATTCTTCA
                 TTATGTTGGGAACTGTGTTCCTTTGGAGGAGGAGAGGCACTCTGCGTTTTAGAGTTTC
                 CAGTTTTTCTGTTCTGTTTTTTCCCCATCTTTGTGGTTTTATCTACCGACTTGCATGT
                 ACAAAGCTTCAACTCATCCTCCTGTCTGGGCCCCCACTTTTAATTCTCATTCTTTGTT
                 ATGCATACAGTCTCAAGCCTTTCTAGGATATTACCAGGGCAGTTGACTGCCTTTAACT
                 G
                 ORF Start: ATG at 31 ORF Stop: TAG at 778
                 SEQ ID NO:10         249 aa MW at 28550.3 kD
NOV3a,           MPTYKIPSQWSNSALASLTSPTWPSSKCTLLPLLILSLLSPFTEQFIVNSLKRPILAP
CG59845-01       LGGKVELSCQLSPPQSAEHMEIRWFQSHYTRPVYLYKDGKDLYGETISKYVERTELLK
Protein Sequence EAIGEGKVTLRILNVSADDDGQYHCFFKDRNVYEESITEVKVSDKLFPWNSIWILILV
                 AILAVLLFFIMLGTVFLWRRRGTLRFRVSSFSVLFFPHLCGFIYRLACTKLQLILLSG
                 PPLLILILCYAYSLKPF

[0283] Further analysis of the NOV3a protein yielded the following properties shown in Table 3B.

TABLE 3B
Protein Sequence Properties NOV3a
PSort     0.8000 probability located in mitochondrial inner membrane;
analysis: 0.6000 probability located in plasma membrane; 0.4000
          probability located in Golgi body; 0.3000 probability
          located in endoplasmic reticulum (membrane)
SignalP   Cleavage site between residues 46 and 47
analysis:

[0284] 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 [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAY44236	Human myelin oligodendrocyte	15 . . . 242	103/233 (44%)	5e−45
	glycoprotein - Homo sapiens, 247 aa.	1 . . . 228	147/233 (62%)
	[WO9960021-A2, 25-NOV-1999]
AAW37543	Human myelin oligodendrocyte	15 . . . 242	102/233 (43%)	1e−44
	glycoprotein - Homo sapiens, 247 aa.	1 . . . 228	147/233 (62%)
	[WO9735879-A1, 02-OCT-1997]
AAR71360	Human MOG - Homo sapiens, 247	15 . . . 242	102/233 (43%)	1e−44
	aa. [W09507096-A, 16-MAR-1995]	1 . . . 228	147/233 (62%)
AAR70182	Human myelin oligonucleotide	15 . . . 242	102/233 (43%)	1e−44
	glycoprotein (MOG) - Homo	1 . . . 228	147/233 (62%)
	sapiens, 247 aa. [WO9506727-A, 09-
	MAR-1995]
AAR71361	Human truncated MOG - Homo	15 . . . 209	90/198 (45%)	4e−40
	sapiens, 203 aa. [WO9507096-A, 16-	1 . . . 197	129/198 (64%)
	MAR-1995]

[0285] 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
Q9BGS7	HYPOTHETICAL 28.2 KDA	15 . . . 242	102/233 (43%)	3e−44
	PROTEIN - Macaca fascicularis (Crab	1 . . . 228	148/233 (62%)
	eating macaque) (Cynomolgus monkey),
	247 aa.
Q96KU9	BA145L22.1.1	15 . . . 242	102/233 (43%)	3e−44
	(MYELIN/OLIGODENDROCYTE	1 . . . 228	147/233 (62%)
	GLYCOPROTEIN (MOG) BETA 1
	(ISOFORM 1)) - Homo sapiens
	(Human), 252 aa.
Q16653	Myelin-oligodendrocyte glycoprotein	15 . . . 242	102/233 (43%)	3e−44
	precursor - Homo sapiens (Human), 247	1 . . . 228	147/233 (62%)
	aa.
A55717	myelin/oligodendrocyte glycoprotein	15 . . . 242	98/233 (42%)	8e−40
	precursor - mouse, 247 aa.	1 . . . 228	139/233 (59%)
CAB89269	BA145L22.1.6	15 . . . 209	90/198 (45%)	1e−39
	(MYELIN/OLIGODENDROCYTE	1 . . . 197	129/198 (64%)
	GLYCOPROTEIN (MOG), ISOFORM
	6) - Homo sapiens (Human), 208 aa.

[0286] PFam analysis indicates that the NOV3a protein contains the domains shown in Table 3E.

TABLE 3E
Domain Analysis of NOV3a
		Identities/
		Similarities
	NOV3a Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
ig: domain 1 of 1	60 . . . 143	13/85 (15%)	0.00063
		54/85 (64%)
ATP-synt_B: domain 1 of	162 . . . 177	7/16 (44%)	8.6
1		14/16 (88%)

Example 4

[0287] 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:11        1536 bp
NOV4a,           TATGTGGGAGGACGGGCTGCCCCACCCCCGCGCGCAGGAACCCTGGTTTAGCTTAAGG
CG59871-01 DNA   GATGGAGGCGGGGACCCCTGCGCAGGCTTGCGGCGTGGGAGGCGGCCGCCCGCGACCT
Sequence         ACGACGCCGCGCGCCGGGAGGCTGAGAGTTCGGCGCCGGGAGGGTCCCGGGGACAGAA
                 GAGCGCCTCGCCCGGTTGCCAAGGCAACCCCACGCGGCTGGAGAAGCCGGCGCTCGCA
                 GCCCGGCCCGGGCCGCTGCCGGAAGTGACGCGAGTTCACCTGCCGAGCGGGGGCTGGG
                 AGGAGGGGCGGAGGGTGCAGAGGTGCCGCCGCCGCCGCGAGCCAGTCGGGAGCGCGCG
                 AGGCGCGGGGAGCCTGGGCACCAGGAGCGAGAGCCGCCTACCTGCAGCCGCCGCCCAC
                 GGCACGGCAGCCACCATGGCGCTCCTGCTGTGCTTCGTGCTCCTGTGCGGAGTAGTGG
                 ATTTCGCCAGAAGTTTGAGTATCACTACTCCTGAAGAGATGATTGAAAAAGCCAAAGG
                 GGAAACTGCCTATCTGCCATGCAAATTTACGCTTAGTCCCGAAGACCAGGGACCGCTG
                 GACATCGAGTGGCTGATATCACCAGCTGATAATCAGAAGGTGGATCAAGTGATTATTT
                 TATATTCTGGAGACAAAATTTATGATGACTACTATCCAGATCTGAAAGGCCGAGTACA
                 TTTTACGAGTAATGATCTCAAATCTGGTGATGCATCAATAAATGTAACGAATTTACAA
                 CTGTCAGATATTGGCACATATCAGTGCAAAGTGAAAAAAGCTCCTGGTGTTGCAAATA
                 AGAAGATTCATCTGGTAGTTCTTGTTAAGCCTTCAGGTGCGAGATGTTACGTTGATGG
                 ATCTGAAGAAATTGGAAGTGACTTTAAGATAAAATGTGAACCAAAAGAAGGTTCACTT
                 CCATTACAGTATGAGTGGCAAAAATTGTCTGACTCACAGAAAATGCCCACTTCATGGT
                 TAGCAGAAATGACTTCATCTGTTATATCTGTAAAAAATGCCTCTTCTGAGTACTCTGG
                 GACATACAGCTGTACAGTCAGAAACAGAGTGGGCTCTGATCAGTGCCTGTTGCGTCTA
                 AACGTTGTCCCTCCTTCAAATAAAGCTGGACTAATTGCAGGAGCCATTATAGGAACTT
                 TGCTTGCTCTAGCGCTCATTGGTCTTATCATCTTTTGCTGTCGTAAAAAGCGCAGAGA
                 AGAAAAATATGAAAAGGAAGTTCATCACGATATCAGGGAAGATGTGCCACCTCCAAAG
                 AGCCGTACGTCCACTGCCAGAAGCTACATCGGCAGTAATCATTCATCCCTGGGGTCCA
                 TGTCTCCTTCCAACATGGAAGGATATTCCAAGACTCAGTATAAACAAGTACCAAGTGA
                 AGACTTTGAACGCACTCCTCAGAGTCCGACTCTCCCACCTGCTAAGGTAGCTGCCCCT
                 AATCTAAGTCGAATGGGCGCGATTCCTGTGATGATTCCCGCACAGAGCAAGGATGGGT
                 CTATAGTATAGAGCCTCCATACATCTCA
                 ORF Start: ATG at 2 ORF Stop: TAG at 1517
                 SEQ ID NO:12        505 aa MW at 54859.8 kD
NOV4a,           MWEDGLPHPRAQEPWFSLRDGGGDPCAGLRRGRRPPATYDAARREAESSAPGGSRGQK
CG59871-01       SASPGCQGNPTRLEKPALAARPGPLPEVTRVHLPSGGWEEGRRVQRCRRRREPVGSAR
Protein Sequence GAGSLGTRSESRLPAAAAHGTAATMALLLCFVLLCGVVDFARSLSITTPEEMIEKAKG
                 ETAYLPCKFTLSPEDQGPLDIEWLISPADNQKVDQVIILYSGDKIYDDYYPDLKGRVH
                 FTSNDLKSGDASINVTNLQLSDIGTYQCKVKKAPGVANKKIHLVVLVKPSGARCYVDG
                 SEEIGSDFKIKCEPKEGSLPLQYEWQKLSDSQKMPTSWLAEMTSSVISVKNASSEYSG
                 TYSCTVRNRVGSDQCLLRLNVVPPSNKAGLIAGAIIGTLLALALIGLIIFCCRKKRRE
                 EKYEKEVHHDIREDVPPPKSRTSTARSYIGSNHSSLGSMSPSNMEGYSKTQYKQVPSE
                 DFERTPQSPTLPPAKVAAPNLSRMGAIPVMIPAQSKDGSIV

[0288] Further analysis of the NOV4a protein yielded the following properties shown in Table 4B.

TABLE 4B
Protein Sequence Properties NOV4a
PSort     0.6000 probability located in plasma membrane; 0.4000
analysis: probability located in 0.3000 probability located in
          microbody (peroxisome)
SignalP   No Known Signal Sequence
analysis:

[0289] 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 4C.

TABLE 4C
Geneseq Results for NOV4a
		NOV4a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAB47270	Human CAR - Homo sapiens, 365 aa.	141 . . . 505	364/365 (99%)	0.0
	[US6245966-B1, 12-JUN-2001]	1 . . . 365	364/365 (99%)
AAW57212	Human coxsackievirus and	141 . . . 505	364/365 (99%)	0.0
	adenovirus receptor - Homo sapiens,	1 . . . 365	364/365 (99%)
	365 aa. [WO9811221-A2, 19-MAR-
	1998]
AAW69697	Human coxsackievirus and Ad2 and	141 . . . 505	364/365 (99%)	0.0
	Ad5 receptor HCAR protein - Homo	1 . . . 365	364/365 (99%)
	sapiens, 365 aa. [WO9833819-A1,
	06-AUG-1998]
AAB50930	Human PRO5723 protein - Homo	141 . . . 483	339/343 (98%)	0.0
	sapiens, 352 aa. [WO200073452-A2,	1 . . . 343	339/343 (98%)
	07-DEC-2000]
AAB65294	Human PRO5723 protein sequence	141 . . . 483	339/343 (98%)	0.0
	SEQ ID NO:505 - Homo sapiens, 352	1 . . . 343	339/343 (98%)
	aa. [WO200073454-A1, 07-DEC-
	2000]

[0290] 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 4D.

TABLE 4D
Public BLASTP Results for NOV4a
		NOV4a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P78310	Coxsackievirus and adenovirus	141 . . . 505	364/365 (99%)	0.0
	receptor precursor (Coxsackievirus B-	1 . . . 365	364/365 (99%)
	adenovirus receptor) (hCAR) (CVB3
	binding protein) - Homo sapiens
	(Human), 365 aa.
Q9UKV4	COXSACKIE AND ADENOVIRUS	141 . . . 479	338/339 (99%)	0.0
	RECEPTOR PROTEIN - Homo	1 . . . 339	338/339 (99%)
	sapiens (Human), 344 aa (fragment).
AAK57804	COXSACKIE VIRUS AND	141 . . . 505	331/365 (90%)	0.0
	ADENOVIRUS RECEPTOR BCAR -	1 . . . 365	345/365 (93%)
	Bos taurus (Bovine), 365 aa.
P97792	Coxsackievirus and adenovirus	141 . . . 505	327/365 (89%)	0.0
	receptor homolog precursor (mCAR) -	1 . . . 365	344/365 (93%)
	Mus musculus (Mouse), 365 aa.
Q9DBJ8	COXSACKIEVIRUS AND	141 . . . 505	327/366 (89%)	0.0
	ADENOVIRUS RECEPTOR - Mus	1 . . . 366	344/366 (93%)
	musculus (Mouse), 366 aa.

[0291] PFam analysis indicates that the NOV4a protein contains the domains shown in Table 4E.

TABLE 4E
Domain Analysis of NOV4a
		Identities/
		Similarities
	NOV4a Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
ig: domain 1 of 2	174 . . . 262	13/90 (14%)	0.0054
		62/90 (69%)
ig: domain 2 of 2	295 . . . 354	11/62 (18%)	1.5e−05
		46/62 (74%)
Adeno_E3_CR2:	372 . . . 417	15/50 (30%)	4.9
domain 1 of 1		24/50 (48%)

Example 5

[0292] 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:13        1302 bp
NOV5a,           ATGAACATGAAATTGCAGATGTCTGTTTTTGACATACTGATTAAAATTCCTTTGGACA
CG59883-01 DNA   CGTATCCAGAAGTGGGATTGATGGATCATAGGTGCGCCAGGCGCGGGGAGCCTAGGAC
Sequence         CTGGAGCGAGAGCCGCCTACCTGCAGCCGCCGCCCACGGCACGGCAGCCACCGTGGCG
                 CTCCTGCTGCGCTTCGTGCTCCTGTGCAGAGTCGCGGATTTCATCAGAGGTTGGAGTA
                 TCACTACTCCTGAGCAGATGATTGAAAAAGCCAAAGGGGAAACTGCCTATCTGCCATG
                 CAAATTTACGCTTAGTCCTGAAGACCAGGGACCACTGGACATCGAGTGGCTGATATCA
                 CCAGCTGATAATCAGAAGGTGGATCAAGTGATTATTTTATATTCTGGAGACAAAAATT
                 ATGATGACTACTATCCAGATCTGAAAGGCCGAGTACATTTTAAGAGTAATGATCTCAA
                 ATCTGGTGATGCATCAATAAATGTAACGAATTTTCAGCTGTCAGATATTGGCACAGAT
                 CAGTGCAAAGTGAAAAGAGCTCCTGGTGTTGCAAATAGGAAGATTCAGCTGGTAGTTC
                 TTGGTAAGCCTTCAGGTACAAGATGTTACGTTGATGGATCAGAAGAAATTGGAAGTGA
                 CTTTAAATTAAAATGTGAACCAAAAGAAGGTTCACTTCCATTACAGTATGAGTGGCAA
                 AAATTGTCTGACTCACAGAAAATGCCCACTTCATGGTTAGCAGAAATGACTTCATCTG
                 TTATATCTGTAAAAAAAAATGCTTCTTCTGAGTACTCTGGGACATACAGCTGTACAAT
                 CAGAAACAGAGTGGGCTCTGATCAGTGCCTGTTGCGTGTAAACGTTGTCCCTCCTTCA
                 AATAAAGCTGGACTAATTGCAGGAGCCATTATAGGAACTTTGCTTGCTCTAGTGCTCA
                 TTGGTCTTATCATCTTTTGCTGTCGTAAAAAGCGCAGAGAAGAAAAATATGAAAAGGA
                 AGTTCATCACGATATCAAGGAAGATGTGCCGCCTCCAAAGAGCCACACGTCCACTGCC
                 AGAAGCTACATAGGCAGTAATCATTCATCCCTGGGATCCATATCTCCTTCCAACATGG
                 AAGGATATTCCAAGACTCAGTATAAACAAGTACCAAGTGAAGACTTTGAACGCACTCC
                 TCAGAGTCCGACTCTCCCACCTGCTAAGGTAGCTGCCCCTAATCTAAGTCGAATGGGC
                 GCGATTCCTGTGATGATTCCCGCACAGAGCAAGGATGGGTCTATAGTATAGAGCCTCC
                 ATACATCTCATCTGTGCTCTCCGTGT
                 ORF Start: ATG at 1 ORF Stop: TAG at 1267
                 SEQ ID NO:14        422 aa MW at 46596.9 kD
NOV5a,           MNMKLQMSVFDILIKIPLDTYPEVGLMDHRCARRGEPRTWSESRLPAAAAHGTAATVA
CG59883-01       LLLRFVLLCRVADFIRGWSITTPEQMIEKAKGETAYLPCKFTLSPEDQGPLDIEWLIS
Protein Sequence PADNQKVDQVIILYSGDKNYDDYYPDLKGRVHFKSNDLKSGDASINVTNFQLSDIGTD
                 QCKVKRAPGVANRKIQLVVLGKPSGTRCYVDGSEEIGSDFKLKCEPKEGSLPLQYEWQ
                 KLSDSQKMPTSWLAEMTSSVISVKKNASSEYSGTYSCTIRNRVGSDQCLLRVNVVPPS
                 NKAGLIAGAIIGTLLALVLIGLIIFCCRKKRREEKYEKEVHHDIKEDVPPPKSHTSTA
                 RSYIGSNHSSLGSISPSNMEGYSKTQYKQVPSEDFERTPQSPTLPPAKVAAPNLSRMG
                 AIPVMIPAQSKDGSIV

[0293] Further analysis of the NOV5a protein yielded the following properties shown in Table 5B.

TABLE 5B
Protein Sequence Properties NOV5a
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 23 and 24
analysis:

[0294] 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 [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAB47270	Human CAR - Homo sapiens, 365 aa.	57 . . . 422	340/366 (92%)	0.0
	[US6245966-B1, 12-JUN-2001]	1 . . . 365	349/366 (94%)
AAW57212	Human coxsackievirus and	57 . . . 422	340/366 (92%)	0.0
	adenovirus receptor - Homo sapiens,	1 . . . 365	349/366 (94%)
	365 aa. [WO9811221-A2, 19-MAR-
	1998]
AAW69697	Human coxsackievirus and Ad2 and	57 . . . 422	340/366 (92%)	0.0
	Ad5 receptor HCAR protein - Homo	1 . . . 365	349/366 (94%)
	sapiens, 365 aa. [WO9833819-A1,
	06-AUG-1998]
AAW57213	Mouse coxsackievirus and	57 . . . 422	316/366 (86%)	0.0
	adenovirus receptor - Mus sp, 376 aa.	1 . . . 365	338/366 (92%)
	[WO9811221-A2, 19-MAR-1998]
AAB50930	Human PRO5723 protein - Homo	57 . . . 400	315/344 (91%)	0.0
	sapiens, 352 aa. [WO200073452-A2,	1 . . . 343	324/344 (93%)
	07-DEC-2000]

[0295] 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
P78310	Coxsackievirus and adenovirus	57 . . . 422	340/366 (92%)	0.0
	receptor precursor (Coxsackievirus B-	1 . . . 365	349/366 (94%)
	adenovirus receptor) (hCAR) (CVB3
	binding protein) - Homo sapiens
	(Human), 365 aa.
AAK57804	COXSACKIE VIRUS AND	59 . . . 422	323/364 (88%)	0.0
	ADENOVIRUS RECEPTOR BCAR -	3 . . . 365	341/364 (92%)
	Bos taurus (Bovine), 365 aa.
P97792	Coxsackievirus and adenovirus	57 . . . 422	317/366 (86%)	0.0
	receptor homolog precursor (mCAR) -	1 . . . 365	339/366 (92%)
	Mus musculus (Mouse), 365 aa.
Q9DBJ8	COXSACKIEVIRUS AND	57 . . . 422	317/367 (86%)	0.0
	ADENOVIRUS RECEPTOR - Mus	1 . . . 366	339/367 (91%)
	musculus (Mouse), 366 aa.
Q9R066	COXSACKIE-ADENOVIRUS-	57 . . . 415	314/359 (87%)	0.0
	RECEPTOR HOMOLOG - Rattus	1 . . . 358	332/359 (92%)
	norvegicus (Rat), 358 aa (fragment).

[0296] PFam analysis indicates that the NOV5a protein contains the domains shown in Table 5E.

TABLE 5E
Domain Analysis of NOV5a
		Identities/
		Similarities
	NOV5a Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
ig: domain 1 of 2	90 . . . 178	12/90 (13%)	37
		62/90 (69%)
ig: domain 2 of 2	211 . . . 271	11/63 (17%)	0.014
		43/63 (68%)
Adeno_E3_CR2:	289 . . . 334	15/50 (30%)	3.2
domain 1 of 1		24/50 (48%)

Example 6

[0297] 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:15        412 bp
NOV6a,           ATGGCCCGGGCCAGGGCCGGGGCGCTGCTGGCGCTTTGGGTGCTCGGGGCCGCCGCGC
CG59901-01 DNA   ATCCGCAGTGCCTGGACTTCAGGCCGCCCTTCCGGCCGACGCAGCCGCTGCGCCTCTG
Sequence         CGCGCAGTACTCGGACTTCGGCTGCTGCGATGAGGGGCGCGACGCCGAGCTGACCCGC
                 CGCTTCTGGGCCCTGGCGAGCCGCGTGGACGCCGCCGAGTGGGCCGCGTGCGCCGCCT
                 ACGCGAGGGACCTGCTGTGCCAGTCCGTGGAGTGGACAGACATGCAAAGAGATAATGA
                 AGTCCTAGCCAAGCTGACTGGCTGGAGCGCCCCTGGCGACGGAGCAGTGACTGCTGTA
                 GAGAACTCACCCTCTCTGGACTACCCTGGTCTGGGCACCACATTTACGTCGTGTGAAT
                 GCTCGCCGTATGCAGCCCACCTCTATGACGCCGAGGACCCATTCACGCCCCTGCGCAC
                 GGTGCCCGGGCTCTGCCAGGATTACTGCCTGGACATGTGGCATAAGTGCCGGGGGCTG
                 TTCCGTCACCTGTCAACTGACCAGGAGCTCTGGGCGCTGGAGGGCAACCTTGCCAGGT
                 TCTGCCGCTACCTGTCCCTGGATGACACGGACTACTGCTTCCCTTACCTGCTGGTCAA
                 CAAGAACCTCAACTCAAACCTGGGCCACGTGGTAGCCGATGCCAAGGGCTGCCTGCAG
                 CTGTGCCTGGAGGAGGTGGCCAACGGGCTGCGCAACCCCGTGGCCATGGTCCATGCCA
                 GGCATGGCACCCACCGCTTCTTCGTGGCCGAGCACGTGCGGCTGGTGTGGGCCTACCT
                 GCCCGACCGCTCGAGGCTGGGGAAGCCTTTCCTGAACATCACCCGCGTGGTCCTCACC
                 TCGCCCTGGGAGGGTGACGAGCGTGGCTTCCTGGGCATTGCCTTCCACCCCAGCTTCC
                 AGCACAACCGCAGGCTCTACGTCTACTACTCAGTGGGTATCCGCAGCAGTGAGTGGAT
                 CCGCATCAGCGAGTTCAGAGTCTCCGAGGATGACGAGAACGCCGTGGACCACAGCTCT
                 GAGAGGATAATCCTGGAGGTCAAAGAACCAGCCTCAAACCACAACGGGGGCCAGCTGC
                 TTTTCGGGGATGACGGGTACCTCTACATCTTCACTGGAGATGGCGGGATGGCCGGAGA
                 CCCCTTTGGGACATTTGGAAATGCCCAAAACAAGTATGTTCAGCTTTTGATTGGCTTG
                 TGGGTTGGTCTCCATATCCCTGGGCTTCTCATACTCTTCCAGAGGTCGGCGCTGCTGG
                 GCAAGGTGCTGCGCATCGACGTGGACCCCGAGGTCTACGCCCTAGGCGTGCGCAACAT
                 GTGGCGCTGCTCCTTCGACCGTGGCGACCCCTCCTCGGGCACTGGCCGCGGGCGCCTC
                 TTCTGCGGCGACGTGGGCCAGAACAAGTTCGAGGAGGTGGACGTGGTGGAGCGCGGCG
                 GCAACTATGGCTGGCGCGCGCGCGAAGGGTTCGAGTGCTACGACCGCAGCCTGTGCGC
                 CAACACCTCTCTCAATGACTTGCTGCCGATTTTCGCCTACCCGCACACGGTTGGCAAG
                 TCGGTCACAGGGGGCTACGTGTACCGGGGCTGCGAGTACCCCAACCTGAACGGCCTCT
                 ACATTTTTGGGGATTTCATGAGCGGGCGTCTGATGTCCCTCCAAGAGAACCCAGGGAC
                 AGGCCAGTGGCAGTACAGTGAGATCTGCATGGGCCACGGCCAGACCTGTGAGTTCCCA
                 GGCCTCATCAACAACTACTACCCGTACATCATCTCCTTCGGGGAGGACGAGGCCGGGG
                 AGCTGTACTTCATGTCGACAGGGGAGCCGAGTGCCACAGCTCCACGCGGAGTTGTCTA
                 CAAAATAATTGACGCATCCAGAGTTCATCCCGAAGACACGGAGCACCCCGCGGCCTAC
                 AGCGCGGGCGCCCACGCGGGCGCCCGCCGAGGGCGCCCCACGGCCGCTCCCCCCGCGC
                 CAACCCCGCGGCCAGCGCGGCCCACCCAGCAGCCAGGGAGCCGGAGGGGCCGCGGGCG
                 GCGGCGGGGGCGGCTGAACTCGGCGAGCCGGGCGTTCCGGGATGGCGAGGTGCGCCTG
                 GTGCGGCCCGCGGGCCTGAGCTCTGGCAGCGGGCGCGTGGAGGTGTTCGTGGGCGGAC
                 GCTGGGGCACCGTGTGCGACGACTCCTGGAACATCAGCGGCGCCGCCGTCGTGTGTCG
                 CCAGCTGGGGTTTGCCTACGCCGTGCGCGCCGTCAAGAGAGCCGAGTTCGGCCAGGGC
                 GGCTCGCTGCCCATTCTGCTGGACGATGTGCGCTGCGCGGGCTGGGAGCGGAACCTGC
                 TGGAGTGCCAGCACAACGGCGTGGGCACCCACAACTGCGAGCACGACGAGGATGCGGG
                 CGTCGTGTGCAGCCACCAGAACCCCGACCTGTAG
                 ORF Start: ATG at 1 ORF Stop: TAG at 2410
                 SEQ ID NO:16        803 aa MW at 88653.7 kD
NOV6a,           MARARAGALLALWVLGAAAHPQCLDFRPPFRPTQPLRLCAQYSDFGCCDEGRDAELTR
CG59901-01       RFWALASRVDAAEWAACAGYARDLLCQSVEWTDMQRDNEVLAKLTGWSAPGDGAVTAV
Protein Sequence ENSPSLDYPGLGTTFTSCECSPYAAHLYDAEDPFTPLRTVPGLCQDYCLDMWHKCRGL
                 FRHLSTDQELWALEGNLARFCRYLSLDDTDYCFPYLLVNKNLNSNLGHVVADAKGCLQ
                 LCLEEVANGLRNPVAMVHARDGTHRFFVAEQVGLVWAYLPDRSRLGKPFLNISRVVLT
                 SPWEGDERGFLGIAFHPSFQHNRRLYVYYSVGIRSSEWIRISEFRVSEDDENAVDHSS
                 ERIILEVKEPASNHNGGQLLFGDDGYLYIFTGDGGMAGDPFGTFGNAQNKYVQLLIGL
                 WVGLHIPGLLILFQRSALLGKVLRIDVDPEVYALGVRNMWRCSFDRGDPSSGTGRGRL
                 FCGDVGQNKFEEVDVVERGGNYGWRAREGFECYDRSLCANTSLNDLLPIFAYPHTVGK
                 SVTGGYVYRGCEYPNLNGLYIFGDFMSGRLMSLQENPGTGQWQYSEICMGHGQTCEFP
                 GLINNYYPYIISFGEDEAGELYFMSTGEPSATAPRGVVYKIIDASRVHPEDTEHPAAY
                 SAGAHAGARRGRPTAAPPAPTPRPARPTQQPGSRRGGGRRRGRLNSASRAFRDGEVRL
                 VRPAGLSSGSGRVEVFVGGRWGTVCDDSWNISGAAVVCRQLGFAYAVRAVKRAEFGQG
                 GSLPILLDDVRCAGWERNLLECQHNGVGTHNCEHDEDAGVVCSHQNPDL

[0298] Further analysis of the NOV6a protein yielded the following properties shown in Table 6B.

TABLE 6B
Protein Sequence Properties NOV6a
PSort     0.4600 probability located in plasma membrane; 0.2073
analysis: probability located in microbody (peroxisome); 0.1000
          probability located in endoplasmic reticulum
          (membrane); 0.1000 probability located in endoplasmic
          reticulum (lumen)
SignalP   Cleavage site between residues 20 and 21
analysis:

[0299] 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 6C.

TABLE 6C
Geneseq Results for NOV6a
		NOV6a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU12201	Human PRO1779 polypeptide	20 . . . 629	343/636 (53%)	0.0
	sequence - Homo sapiens, 724	42 . . . 605	410/636 (63%)
	aa.[WO200140466-A2, 07-JUN-2001]
AAB25594	Protein encoded by human secreted	20 . . . 629	343/636 (53%)	0.0
	protein gene #1 - Homo sapiens, 724	42 . . . 605	410/636 (63%)
	aa. [WO200029435-A1, 25-MAY-
	2000]
AAB94773	Human protein sequence SEQ ID	223 . . . 629	269/432 (62%)	e−159
	NO: 15860 - Homo sapiens, 529	2 . . . 410	319/432 (73%)
	aa. [EP1074617-A2, 07-FEB-2001]
AAB25576	Protein encoded by human secreted	223 . . . 629	269/432 (62%)	e−159
	protein gene #1 - Homo sapiens, 529	2 . . . 410	319/432 (73%)
	aa. [WO200029435-A1, 25-MAY-
	2000]
AAY97561	Mouse Hedgehog interacting protein	93 . . . 631	183/615 (29%)	5e−59
	sequence - Mus musculus, 700	50 . . . 593	272/615 (43%)
	aa. [WO200074706-A1, 14-DEC-2000]

[0300] 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 6D.

TABLE 6D
Public BLASTP Results for NOV6a
		NOV6a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96JK4	KIAA1822 PROTEIN - Homo	299 . . . 803	464/556 (83%)	0.0
	sapiens (Human), 533 aa	1 . . . 533	466/556 (83%)
	(fragment).
Q91638	GENE 5 PROTEIN - Xenopus	5 . . . 626	346/648 (53%)	0.0
	laevis (African clawed frog), 995	39 . . . 606	419/648 (64%)
	aa.
Q9H8A0	CDNA FLJ13840 FIS, CLONE	223 . . . 629	269/432 (62%)	e−159
	THYRO1000783,	2 . . . 410	319/432 (73%)
	MODERATELY SIMILAR TO
	XENOPUS LAEVIS TAIL-
	SPECIFIC THYROID
	HORMONE UP-REGULATED
	(GENE 5) MRNA - Homo sapiens
	(Human), 529 aa.
Q9D2G9	4930507C10RIK PROTEIN - Mus	248 . . . 629	260/407 (63%)	e−148
	musculus (Mouse), 497 aa.	1 . . . 383	299/407 (72%)
Q96BT4	SIMILAR TO HYPOTHETICAL	223 . . . 475	168/278 (60%)	1e−91
	PROTEIN FLJ13840 - Homo	2 . . . 256	195/278 (69%)
	sapiens (Human), 256 aa.

[0301] PFam analysis indicates that the NOV6a protein contains the domains shown in Table 6E.

TABLE 6E
Domain Analysis of NOV6a
		Identities/
		Similarities
	NOV6a	for the
Pfam Domain	Match Region	Matched Region	Expect Value
SRCR:	699 . . . 797	49/115 (43%)	6.2e−25
domain 1 of 1		73/115 (63%)

Example 7

[0302] 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:17         2111 bp
NOV7a,           GTCCTCTGTGACCTTCTTCTTGGCCCTCTTCCTGGCAGATAAGTGCTCTGGTTGTACA
CG88748-01 DNA   TGGAGGATGACCGAAAAAACCAATGGTGTGAAGAGCTCCCCAGCCAATAATCACAACC
Sequence         ATCATGCACCTCCTGCCATCAAGGCCAATGGCAAAGATGACCACAGGACAAGCAGCAG
                 GCCACACTCTGCAGCTGACGATGACACCTCCTCAGAACTGCAGAGGCTGGCAGACGTG
                 GATGCCCCACAGCAGGGAAGGAGTGGCTTCCGCAGGATAGTTCGCCTGGTGGGGATCA
                 TCAGAGAATGGGCCAACAAGAATTTCCGAGAGGAGGAACCTAGGCCTGACTCATTCCT
                 CGAGCGTTTTCGTGGGCCTGAACTCCAGACTGTGACCACACAGGAGGGGGATGGCAAA
                 GGCGACAAGGATGGCGAGGACAAAGGCACCAAGAAGAAATTTGAACTATTTGTCTTGG
                 ACCCAGCTGGGGATTGGTACTACTGCTGGCTATTTGTCATTGCCATGCCCGTCCTTTA
                 CAACTGGTGCCTGCTGGTGGCCAGAGCCTGCTTCAGTGACCTACAGAAAGGCTACTAC
                 CTGGTGTGGCTGGTGCTGGATTATGTCTCAGATGTCGTCTACATTGCGGACCTCTTCA
                 TCCGATTGCGCACAGGTTTCCTGGAGCAGGGGCTGCTGGTCAAAGATACCAAGAAACT
                 GCGAGACAACTACATCCACACCCTGCAGTTCAAGCTGGATGTGGCTTCCATCATCCCC
                 ACTGACCTGATCTATTTTGCTGTGGACATCCACAGCCCTGAGGTGCGCTTCAACCGCC
                 TCCTGCACTTTGCCCGCATGTTTGAGTTCTTTGACCGGACAGAGACACGCACCAACTA
                 CCCTAACATCTTCCGCATCAGCAACCTTGTCCTCTACATCTTGGTCATCATCCACTGG
                 AATGCCTGCATCTATTATGCCATCTCCAAATCCATAGGCTTTGGGGTCGACACCTGGG
                 TTTACCCAAACATCACTGACCCTGAGTATGGCTACCTGGCTAGGGAATACATCTATTG
                 CCTTTACTGGTCCACACTGACTCTCACTACCATTGGGGAGACACCACCCCCTGTAAAG
                 GATGAGGAGTACCTATTTGTCATCTTTGACTTCCTGATTGGCGTCCTCATCTTTGCCA
                 CCATCGTGGGAAATGTGGGCTCCATGATCTCCAACATGAATGCCACCCGGGCACAGTT
                 CCAGGCTAAGATCGATGCCGTGAAACACTACATGCAGTTCCGAAAGGTCAGCAAGGGG
                 ATGGAAGCCAAGGTCATTAGGTGGTTTGACTACTTGTGGACCAATAAGAAGACAGTGG
                 ATGAGCGAGAAATTCTCAAGAATCTGCCAGCCAAGCTCAGGGCTGAGATAGCCATCAA
                 TGTCCACTTGTCCACACTCAAGAAAGTGCGCATCTTCCATGATTGTGAGGCTGGCCTG
                 CTGGTAGAGCTGCTACTGAAACTCCGTCCTCAGGTCTTCAGTCCTGGGGATTACATTT
                 GCCGCAAAGGGGACATCGGCAAGGAGATGTACATCATTAAGGAGGGCAAACTGGCAGT
                 GGTGGCTGATGATGGTGTGACTCAGTATGCTCTGCTGTCGGCTGGAAGCTGCTTTGGC
                 GAGATCAGTATCCTTAACATTAAGGGCAGTAAAATGGGCAATCGACGCACAGCTAATA
                 TCCGCAGCCTGGGCTACTCAGATCTCTTCTGCTTGTCCAAGGATGATCTTATGGAAGC
                 TGTGACTGAGTACCCTGATGCCAAGAAAGTCCTAGAAGAGAGGGGTCGGGAGATCCTC
                 ATGAAGGAGGGACTGCTGGATGAGAACGAAGTGGCAACCAGCATGGAGGTCGACGTGC
                 AGGAGAAGCTAGGGCAGCTGGAGACCAACATGGAAACCTTGTACACTCGCTTTGGCCG
                 CCTGCTGGCTGAGTACACGGGGGCCCAGCAGAAGCTCAAGCAGCGCATCACAGTTCTG
                 GAAACCAAGATGAAACAGAACAATGAAGATGACTACCTGTCTGATGGGATGAACAGCC
                 CTGAGCTGGCTGCTGCTGACGAGCCATAAGACCTGGGGCCCAACTGCCTCTCCAGCAT
                 TGGCCTTGGCCTTGATCCCAGAA
                 ORF Start: ATG at 65 ORF Stop: TAA at 2057
                 SEQ ID NO:18         664 aa MW at 76047.3 kD
NOV7a,           MTEKTNGVKSSPANNHNHHAPPAIKANGKDDHRTSSRPHSAADDDTSSELQRLADVDA
CG88748-01       PQQGRSGFRRIVRLVGIIREWANKNFREEEPRPDSFLERFRGPELQTVTTQEGDGKGD
Protein Sequence KDGEDKGTKKKFELFVLDPAGDWYYCWLFVIAMPVLYNWCLLVARACFSDLQKGYYLV
                 WLVLDYVSDVVYIADLFIRLRTGFLEQGLLVKDTKKLRDNYIHTLQFKLDVASIIPTD
                 LIYFAVDIHSPEVRFNRLLHFARMFEFFDRTETRTNYPNIFRISNLVLYILVIIHWNA
                 CIYYAISKSIGFGVDTWVYPNITDPEYGYLAREYIYCLYWSTLTLTTIGETPPPVKDE
                 EYLFVIFDFLIGVLIFATIVGNVGSMISNMNATRAEFQAKIDAVKHYMQFRKVSKGME
                 AKVIRWFDYLWTNKKTVDEREILKNLPAKLRAEIAINVHLSTLKKVRIFHDCEAGLLV
                 ELVLKLRPQVFSPGDYICRKGDIGKEMYIIKEGKLAVVADDGVTQYALLSAGSCFGEI
                 SILNIKGSKMGNRRTANIRSLGYSDLFCLSKDDLMEAVTEYPDAKKVLEERGREILMK
                 EGLLDENEVATSMEVDVQEKLGQLETNMETLYTRFGRLLAEYTGAQQKLKQRITVLET
                 KMKQNNEDDYLSDGMNSPELAAADEP

[0303] Further analysis of the NOV7a protein yielded the following properties shown in Table 7B.

TABLE 7B
Protein Sequence Properties NOV7a
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   No Known Signal Sequence
analysis:

[0304] 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 7C.

TABLE 7C
Geneseq Results for NOV7a
		NOV7a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/	Match	the Matched	Expect
Identifier	Length [Patent #, Date]	Residues	Region	Value
AAE04894	Human transporter and ion channel-	1 . . . 664	664/664 (100%)	0.0
	7 (TRICH-7) protein - Homo	1 . . . 664	664/664 (100%)
	sapiens, 664 aa. [WO200146258-
	A2, 28-JUN-2001]
AAM47673	MOL10b protein sequence - Homo	124 . . . 657	290/540 (53%)	e−170
	sapiens, 575 aa. [WO200181578-	18 . . . 555	394/540 (72%)
	A2, 01-NOV-2001]
AAM47672	MOL10a protein sequence -	132 . . . 657	290/534 (54%)	e−168
	Unidentified, 578 aa.	27 . . . 558	391/534 (72%)
	[WO200181578-A2, 01-NOV-2001]
ABG27071	Novel human diagnostic protein	198 . . . 399	151/202 (74%)	3e−88
	#27062 - Homo sapiens, 259 aa.	57 . . . 258	176/202 (86%)
	[WO200175067-A2, 11-OCT-2001]
ABG27071	Novel human diagnostic protein	198 . . . 399	151/202 (74%)	3e−88
	#27062 - Homo sapiens, 259 aa.	57 . . . 258	176/202 (86%)
	[WO200175067-A2, 11-OCT-2001]

[0305] 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 7D.

TABLE 7D
Public BLASTP Results for NOV7a
		NOV7a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
S35691	cyclic nucleotide-gated channel protein-	1 . . . 664	624/664 (93%)	0.0
	rabbit, 732 aa.	69 . . . 732	643/664 (95%)
Q28718	Cyclic-nucleotide-gated olfactory	1 . . . 664	624/664 (93%)	0.0
	channel (Cyclic-nucleotide-gated cation	1 . . . 664	643/664 (95%)
	channel 2) (CNG channel 2) (CNG-2)
	(CNG2) (Aorta CNG channel)
	(RACNG) - Oryctolagus cuniculus
	(Rabbit), 664 aa.
Q03041	Cyclic-nucleotide-gated olfactory	1 . . . 657	618/657 (94%)	0.0
	channel (Cyclic-nucleotide-gated cation	1 . . . 657	639/657 (97%)
	channel 2) (CNG channel 2) (CNG-2)
	(CNG2) - Bos taurus (Bovine), 663 aa.
Q62398	Cyclic-nucleotide-gated olfactory	1 . . . 662	618/663 (93%)	0.0
	channel (Cyclic-nucleotide-gated cation	2 . . . 664	636/663 (95%)
	channel 2) (CNG channel 2) (CNG-2)
	(CNG2) - Mus musculus (Mouse), 664
	aa.
Q00195	Cyclic-nucleotide-gated olfactory	1 . . . 662	615/663 (92%)	0.0
	channel (Cyclic-nucleotide-gated cation	2 . . . 664	636/663 (95%)
	channel 2) (CNG channel 2) (CNG2)
	(CNG-2) (OCNC1) - Rattus norvegicus
	(Rat), 664 aa.

[0306] PFam analysis indicates that the NOV7a protein contains the domains shown in Table 7E.

TABLE 7E
Domain Analysis of NOV7a
		Identities/
		Similarities
	NOV7a Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
ion_trans:	174 . . . 371	35/236 (15%)	5.1e−22
domain 1 of 1		152/236 (64%)
cNMP_binding:	469 . . . 565	34/120 (28%)	1.4e−25
domain 1 of 1		81/120 (68%)

Example 8

[0307] 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:19         2273 bp
NOV8a,           TCCTTTCCTTTCCCATTGTCTTTGGATGACTATCGCTGGGCTGGGACATGAGGCGGGC
CG90021-01 DNA   AGAGGCGCGGGTCACCCTTAGGACCCCCCTCTTGCTGCTGGGGCTCTGGGCGCTCCTG
Sequence         GCTCCGGTCCGGTGTTCTCAAGGCCGTCCCTTGTGGCACTATGCCTCCTCCGAGGTGG
                 TGATTCCCAGGAAGGAGACACACCATAGCAAAGGCCTTCAGTTTCCCGGCTGGCTGTC
                 CTACAGCCTGTGTTTTGGGTTTTGGGGTCAAAGACACGTCATTCACATGCGGAGGAAA
                 CACCTTCTTTGGCCTAGACATCTGCTGGTGACAACTCAGGATGACCAAGGAGTCTTGC
                 AGATGGGTGACCCCTACATCCCTCCAGACTGCTACTACCTCGGCTACCTGGAGGAGGT
                 GCCTCTGTCCATGGTCACCGTCGACACGTGCTATGGGGACCTCAGAGGCATCATGAGG
                 CTGGACGACCTTGCGTACGAAATCAAACCCCTCCAGGATTCCCGCAGGTTTGAACATG
                 TTGTTTTTCAGATAGTCGCCGACCCCAACGCAACAGGGCCCACATTTAGAGATGATGA
                 CAATGAGACAGACCCCCTGTTCTCTGAAGCAAATGACAGCATGAATCCCAGGATATCT
                 AATTCGCTGTATAGTTCTCATAGAGGCAATATAAAAGGCCACGTTCAATGTTCCAATT
                 CATATTATCGCATATATGGCAATATTACAACTTGTTCCAAAGAGGTGGTCCAGATGTT
                 CAGTCTCATTGACAGCATTGCTCAAAATATTGATCTGCGGTACTATATTTATCTTTTG
                 ACCATATATAATAATCGTGACCCAGCCCCTGTGAATGAATATCGAATTCAGAGTGCAA
                 TGTTTACCTATTTTAAAACAACTTTTTTTGATACTTTTCATGTTCATTCATCCACACT
                 ACTTATTAAATACGTGCCACATGAATCTAACTATGAACCTGAAAGGTATAACTTCTGT
                 TCCCGTATAGCCCTGTTACACATTGGTACTCCAGGCAGACATTATTTATTGGTAGCCG
                 TCATAATAACCCAGACACAGATGAGAAGTATTCGTCTGGAGTATGATGATAACTACTG
                 CACATGTCAGAGAAGGGCCTCCTGCATTATGCAGCGATTTCCTGGGATGACAGATGCG
                 TTCAGTAACTGTTCTTATGGACATGCACAAAATTGTTTTATACATTCAGGCCGGTGTG
                 TTTTTGAAACACTTGCTCCTGTGTATAACGAAACCATGACAACGGTTCGCTGTGGAAA
                 CCTCATAGTGGAGGGGAGGGAGGAATGTGACTGTGGCTCCTTCAAGCAGTGTTATGCC
                 AGTTATTGCTGCCAAAGTGACTGTCACTTAACACCGGGGAGCATCTGCCATATAGGAG
                 AGTGCTGTACAAACTGCAGCTTCTCCCCACCAGGGACTCTCTGCAGACCTATCCAAAA
                 TATATGTGACCTTCCACAGTACTGTCACGGGACCACCGTGACATGTCCCGCAAACGTT
                 TATATGCAAGATGGAACCCCGTGCACTGAAGAAGGCTACTGCTATCGTGGGAACTGCA
                 CTGATCGCAATGTGCTCTGCAAGGCGATCTTTGGTGTCAGTGCTGAGGATGCTCCCGA
                 GGTCTGCTATGACATAAATCTTGAAAGCTACCGATTTGGACATTGTATTAGACAACAA
                 ACATATCTCAGCTACCAGGCTTGTGCAGGAATAGATAAGTTTTGTGGAAGACTGCAGT
                 GTACCAATGTGACCCATCTTCCCCGGCTGCAGGAACGTGTTTCATTCCATCACTCAGT
                 GAGAGGAGGGTTTCAGTGTTTTGGACTGGATGAACACCATGCAACAGACACGACTGAT
                 GTTGGGCGTGTGATAGATGGCACTCCTTGTGTTCATGGAAACTTCTGTAATAACACCC
                 AGTGCAATGTGACTATCACTTCACTGGGCTACAACTGCCACCCTCACAAGTGCGGTCA
                 TAGAGGAGTCTGCAACAACAGAAGGAACTGCCATTGCCATATAGGCTGGGATCCTCCA
                 CTGTGCCTAAGAAGAGGTGCTGGTGGGAGTGTCAACAGCGGGCCACCTCCAAAAAGAA
                 CACGTTCCGTCAAACAAAGCCAGCAATCAGTGATGTATCTGAGAGTGGTCTTTGGTCG
                 TATTTACGCCTTCATAATTGCACTGCTCTTTGGGACAGCCAAAAATGTGCGAACTATC
                 AGGACCACCACCGTTAAGGAAGGGACAGTTACTAACCCTGAATAACACTAATTCAGCC
                 TCCCGATCCCT
                 ORF Start: ATG at 48 ORF Stop: TAA at 2247
                 SEQ ID NO:20         733 aa MW at 83206.8 kD
NOV8a,           MRRAEARVTLRTPLLLLGLWALLAPVRCSQGRPLWHYASSEVVIPRKETHHSKGLQFP
CG90021-01       GWLSYSLCFGFWGQRHVIHMRRKHLLWPRHLLVTTQDDQGVLQMGDPYIPPDCYYLGY
Protein Sequence LEEVPLSMVTVDTCYGDLRGIMRLDDLAYEIKPLQDSRRFEHVVFQIVAEPNATGPTF
                 RDDDNETDPLFSEANDSMNPRISNSLYSSHRGNIKGHVQCSNSYYRIYGNITTCSKEV
                 VQMFSLIDSIAQNIDLRYYIYLLTIYNNRDPAPVNEYRIQSAMFTYFKTTFFDTFHVH
                 SSTLLIKYVPHESNYEPERYNFCSRIALLHIGTPGRHYLLVAVIITQTQMRSIGLEYD
                 DNYCTCQRRASCIMQRFPGMTDAFSNCSYGHAQNCFIHSGRCVFETLAPVYNETMTTV
                 RCGNLIVEGREECDCGSFKQCYASYCCQSDCHLTPGSICHIGECCTNCSFSPPGTLCR
                 PIQNICDLPEYCHGTTVTCPANVYMQDGTPCTEEGYCYRGNCTDRNVLCKAIFGVSAE
                 DAPEVCYDINLESYRFGHCIRQQTYLSYQACAGIDKFCGRLQCTNVTHLPRLQERVSF
                 HHSVRGGFQCFGLDEHHATDTTDVGRVIDGTPCVHGNFCNNTQCNVTITSLGYNCHPQ
                 KCGHRGVCNNRRNCHCHIGWDPPLCLRRGAGGSVNSGPPPKRTRSVKQSQQSVMYLRV
                 VFGRIYAFIIALLFGTAKNVRTIRTTTVKEGTVTNPE

[0308] Further analysis of the NOV8a protein yielded the following properties shown in Table 8B.

TABLE 8B
Protein Sequence Properties NOV8a
PSort     0.4600 probability located in plasma membrane; 0.3000
analysis: probability located in lysosome (membrane); 0.2800
          probability located in endoplasmic reticulum (membrane);
          0.1000 probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 32 and 33
analysis:

[0309] 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 [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAU72892	Human metalloprotease partial	1 . . . 733	639/734 (87%)	0.0
	protein sequence #4 - Homo sapiens,	1 . . . 731	669/734 (91%)
	731 aa. [WO200183782-A2, 08-
	NOV-2001]
AAE15652	Human disintegrin-like protein,	1 . . . 733	609/740 (82%)	0.0
	NOV3 - Homo sapiens, 737 aa.	1 . . . 737	645/740 (86%)
	[WO200194416-A2, 13-DEC-2001]
AAE14340	Human protease PRTS-5 protein -	447 . . . 733	253/287 (88%)	e−157
	Homo sapiens, 576 aa.	294 . . . 576	263/287 (91%)
	[WO200183775-A2, 08-NOV-2001]
AAB47561	Protease PRTS-3 - Homo sapiens,	1 . . . 329	270/335 (80%)	e−153
	559 aa. [WO200171004-A2, 27-SEP-	1 . . . 332	283/335 (83%)
	2001]
AAY28655	Human SVPH1-8 protease - Homo	8 . . . 676	243/692 (35%)	e−123
	sapiens, 722 aa. [WO9936549-A1,	8 . . . 675	365/692 (52%)
	22-JUL-1999]

[0310] 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
Q28484	TESTICULAR	1 . . . 733	622/734 (84%)	0.0
	METALLOPROTEASE-LIKE,	1 . . . 732	666/734 (89%)
	DISINTEGRIN-LIKE, CYSTEINE-
	RICH PROTEIN IVA - Macaca
	fascicularis (Crab eating macaque)
	(Cynomolgus monkey), 732 aa.
Q28485	TESTICULAR	20 . . . 733	603/715 (84%)	0.0
	METALLOPROTEASE-LIKE,	1 . . . 713	651/715 (90%)
	DISINTEGRIN-LIKE, CYSTEINE-
	RICH PROTEIN IVB - Macaca
	fascicularis (Crab eating macaque)
	(Cynomolgus monkey), 713 aa
	(fragment).
O19050	CELLULAR DISINTEGRIN ADAM	4 . . . 733	424/736 (57%)	0.0
	6D - Oryctolagus cuniculus (Rabbit),	4 . . . 731	526/736 (70%)
	731 aa.
O19051	CELLULAR DISINTEGRIN ADAM	14 . . . 733	415/724 (57%)	0.0
	6E - Oryctolagus cuniculus (Rabbit),	10 . . . 730	518/724 (71%)
	730 aa.
P70535	TMDC IV PROTEIN - Rattus	1 . . . 720	385/728 (52%)	0.0
	norvegicus (Rat), 751 aa.	8 . . . 732	487/728 (66%)

[0311] PFam analysis indicates that the NOV8a protein contains the domains shown in Table 8E.

TABLE 8E
Domain Analysis of NOV8a
		Identities/
		Similarities
	NOV8a Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
Pep_M12B_propep:	77 . . . 192	42/119 (35%)	1.3e−44
domain 1 of 1		102/119 (86%)
Reprolysin: domain 1 of 1	216 . . . 395	45/210 (21%)	0.00095
		108/210 (51%)
metalthio: domain 1 of 1	395 . . . 458	14/67 (21%)	7
		32/67 (48%)
disintegrin: domain 1 of 1	414 . . . 489	32/76 (42%)	2.2e−18
		44/76 (58%)

Example 9

[0312] 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:21	1677 bp
NOV9a,	TTAATCTTCTGTGGCAGAAATGCAATGGCACATCGTGATTCTGAGATGAAAGAAGAAT
CG90709-01 DNA	GTCTAAGGGAAGACCTGAAGTTTTACTTCATGAGCCCTTGTGAAAAATACCGAGCCAG
Sequence	ACGCCAGATTCCGTGGAAACTGGGTTTGCAGATTTTGAAGATAGTCATGGTCACCACA
	CAGCTTGTTCGTTTTGGTTTAAGTAACCAGCTGGTCGTTGCTTTCAAAGAAGATAACA
	CTGTTGCTTTTAAGCACTTGTTTTTGAAAGGATATTCTGGTACAGATGAAGATGACTA
	CAGCTGCAGTGTATATACTCAAGAGGATGCCTATGAGAGCATCTTTTTTGCTATTAAT
	CAGTATCATCAGCTAAAGGACATTACCCTGGGGACCCTTGGTTATGGAGAAAATGAAG
	ACAATAGAATTGGCTTAAAAGTCTGTAAGCAGCATTACAAGAAAGGGACCATGTTTCC
	TTCTAATGAGACACTGAATATTGACAACGACGTTGAGCTCAACTGTGGGGTTGTGGCG
	ATATACATTTTAAAGTGTTATTCCCTAAGAGATATTATGACAATTTATACCTTTCAAT
	ATATTTTATTCAGGCTCTTACAGGTTGAAATCTCCTTTCATCTTAAAGGCATTGACCT
	ACAGACAATTCATTCCCGTGAGTTACCAGACTGTTATGTCTTTCAGAATACGATTATC
	TTTGACAATAAAGCTCACAGTGGCAAAATCAAAATCTATTTTCACAGTGATGCCAAAA
	TTGAAGAATGTAAAGACTTGAACATATTTGGATCTAGTAAGTATGCTCTGGTGTTTGA
	TGCATTTGTCATTGTGATTTGCTTGGCATCTCTTATTCTGTGTACAAGATCCATTGTT
	CTTGCTCTAAGGTTACGGAGATTTCTAAATTTCTTCCTGGAGAAGTACAAGCGGCCTG
	TGTGTGACACCGACCAGTGGGAGTTCATCAACGGCTGGTATGTCCTGGTGATTATCAG
	CGACCTAATGACAATCATTGGCTCCATATTAAAAATGGAAATCAAACCAAAGAATCTC
	ACAAACTATGATCTCTGCAGCATTTTTCTTGGAACCTCTACGCTCTTGGTTTGGGTTG
	GAGTCATCAGATACCTGGGTTATTTCCAGGCATATAATGTACTGATTTTAACAATGCA
	GGCCTCACTGCCAAAAGTTCTTCGGTTTTGTGCTTGTGCTGGTATGATTTATCTGGGT
	TACACATTCTGTGGCTGGATTGTCTTAGGACCATACCATCTACAGTTTGAAAATCTGA
	ACACAGTTGCTGAGTGTCTGTTTTCTCTGGTCAACGGTGATGACATGTTTGCAACCTT
	TGCCCAAATCCAGCAGAAGAGCATCTTGGTGTGGCTGTTCAGTCGTCTGTATTTATAT
	TCCTTCATCAGCCTTTTTATATATATGATTCTCAGTCTTTTTATTGCACTTATTACAG
	ATTCTTATGACACCATTAAGAAATTCCAACAGAATGGGTTTCCTGAAACGGATTTGCA
	GGAATTCCTGAAGGAATGCAGTAGCAAAGAAGAGTATCAGAAAGAGTCCTCAGCCTTC
	CTGTCCTGCATCTGCTGTCGGAGGAGGTCAGTATCATGTTTATTCTCCATGCTCCTGA
	GATGGGCTGTTCTGTTGTCTTAAGAAAGAGCCCCTCCAAGATTACCATTACAT
	ORF Start: ATG at 25	ORF Stop: TAA at 1645
	SEQ ID NO:22	540 aa MW at 62760.5 kD
NOV9a,	MAHRDSEMKEECLREDLKFYFMSPCEKYRARRQIPWKLGLQILKIVMVTTQLVRFGLS
CG90709-01	NQLVVAFKEDNTVAFKHLFLKGYSGTDEDDYSCSVYTQEDAYESIFFAINQYHQLKDI
Protein Sequence	TLGTLGYGENEDNRIGLKVCKQHYKKGTMFPSNETLNIDNDVELNCGVVAIYILKCYS
	LRDIMTIYTFQYILFRLLQVEISFHLKGIDLQTIHSRELPDCYVFQNTIIFDNKAHSG
	KIKIYFDSDAKIEECKDLNIFGSSKYALVFDAFVIVICLASLILCTRSIVLALRLRRF
	LNFFLEKYKRPVCDTDQWEFINGWYVLVIISDLMTIIGSILKMEIKAKNLTNYDLCSI
	FLGTSTLLVWVGVIRYLGYFQAYNVLILTMQASLPKVLRFCACAGMIYLGYTFCGWIV
	LGPYHLQFENLNTVAECLFSLVNGDDMFATFAQIQQKSILVWLFSRLYLYSFISLFIY
	MILSLFIALITDSYDTIKKFQQNGFPETDLQEFLKECSSKEEYQKESSAFLSCICCRR
	RSVSCLFSMLLRWAVLLS
	SEQ ID NO:23	1671 bp
NOV9b,	TTAAAATTAATCTTCTGTGGCAGAAATGCAATGGCACATCGTGATTCTGAGATGAAAG
CG90709-02 DNA	AAGAATGTCTAAGGGAAGACCTGAAGTTTTACTTCATGAGCCCTTGTGAAAAATACCG
Sequence	AGCCAGACGCCAGATTCCGTGGAAACTGGGTTTGCAGATTTTGAAGATAGTCATGGTC
	ACCACACAGCTTGTTCGTTTTGGTTTAAGTAACCAGCTGGTGGTTGCTTTCAAAGAAG
	ATAACACTGTTGCTTTTAAGCACTTGTTTTTGAAAGGATATTCTGGTACAGATGAAGA
	TGACTACAGCTGCAGTGTATATACTCAAGAGGATGCCTATGAGAGCATCTTTTTTGCT
	ATTAATCAGTATCATCAGCTAAAGGACATTACCCTGGGGACCCTTGGTTATGGAGAAA
	ATGAAGACAATAGAATTGGCTTAAAAGTCTGTAAGCAGCATTACAAGAAAGGGACCAT
	GTTTCCTTCTAATGAGACACTGAATATTGACAACGACGTTGAGCTAGATTGTGTTCAA
	TTAGACCTTCAGGACCTCTCCAAGAAGCCTCCGGACTGGAAGAACTCATCATTCTTCA
	GACTGGAATTTTATCGGCTCTTACAGGTTGAAATCTCCTTTCATCTTAAAGGCATTGA
	CCTACAGACAATTCATTCCCGTGAGTTACCAGACTGTTATGTCTTTCAGAATACGATT
	ATCTTTGACAATAAAGCTCACAGTGGCAAAATCAAAATCTATTTTGACAGTGATGCCA
	AAATTGAAGAATGTAAAGACTTGAACATATTTGGATCAGCTCAGAAAAATGCTCAGTA
	TGTCCTGGTGTTTGATGCATTTGTCATTGTGATTTGCTTGGCATCTCTTATTCTGTGT
	ACAAGATCCATTGTTCTTGCTCTAAGGTTACGGAACAGATTTCTAAATTTCTTCCTGG
	AGAAGTACAAGCGGCCTGTGTGTGACACCGACCAGTGGGAGTTCATCAACGGCTGGTA
	TGTCCTGGTGATTATCAGCGACCTAATGACAATCATTGGCTCCATATTAAAAATGGAA
	ATCAAAGCAAAGAATCTCACAAACTATGATCTCTGCAGCATTTTTCTTGGAACCTCTA
	CGCTCTTGGTTTGGGTTGGAGTCATCAGATACCTGGGTTATTTCCAGGCATATAATGT
	ACTGATTTTAACAATGCAGGCCTCACTGCCAAAAGTTCTTCGGTTTTGTGCTTGTGCT
	GGTATGATTTATCTGGGTTACACATTCTGTGGCTGGATTGTCTTAGGACCATACCATG
	ACAAGTTTGAAAATCTGAACACAGTTGCTGAGTGTCTGTTTTCTCTGGTCAACGGTGA
	TGACATGTTTGCAACCTTTGCCCAAATCCAGCAGAAGAGCATCTTGGTGTGGCTGTTC
	AGTCGTCTGTATTTATATTCCTTCATCAGCCTTTTTATATATATGATTCTCAGTCTTT
	TTATTGCACTTATTACAGATTCTTATGACACCATTAAGAAATTCCAACAGAATGGGTT
	TCCTGAAACGGATTTGCAGGAATTCCTGAAGGAATGCAGTAGCAAAGAAGAGTATCAG
	AAAGAGTCCTCAGCCTTCCTGTCCTGCATCTGCTGTCGGAGGAGGTCAGTATCATGTT
	TATTCTCCATGCTCCTGAGATGGGCTGTTCTGTTGTCTTAAGAAAGA
	ORF Start: ATG at 31	ORF Stop: TAA at 1663
	SEQ ID NO:24	544 aa MW at 63298.8 kD
NOV9b,	MAHRDSEMKEECLREDLKFYFMSPCEKYRARRQIPWKLGLQILKIVMVTTQLVRFGLS
CG90709-02	NQLVVAFKEDNTVAFKHLFLKGYSGTDEDDYSCSVYTQEDAYESIFFAINQYHQLKDI
Protein Sequence	TLGTLGYGENEDNRIGLKVCKQHYKKGTMFPSNETLNIDNDVELDCVQLDLQDLSKKP
	PDWKNSSFFRLEFYRLLQVEISFHLKGIDLQTIHSRELPDCYVFQNTIIFDNKAHSGK
	IKIYFDSDAKIEECKDLNIFGSAQKNAQYVLVFDAFVIVICLASLILCTRSIVLALRL
	RKRFLNFFLEKYKRPVCDTDQWEFINGWYVLVIISDLMTIIGSILKMEIKAKNLTNYD
	LCSIFLGTSTLLVWVGVIRYLGYFQAYNVLILTMQASLPKVLRFCACAGMIYLGYTFC
	GWIVLGPYHDKFENLNTVAECLFSLVNGDDMFATFAQIQQKSILVWLFSRLYLYSFIS
	LFIYMILSLFIALITDSYDTIKKFQQNGFPETDLQEFLKECSSKEEYQKESSAFLSCI
	CCRRRSVSCLFSMLLRWAVLLS
	SEQ ID NO:25	2130 bp
NOV9c,	TTAAAATTAATCTTCTGTGGCAGAAATGCAATGGCACATCGTGATTCTGAGATGAAAG
CG90709-03 DNA	AAGAATGTCTAAGGGAAGACCTGAAGTTTTACTTCATGAGCCCTTGTGAAAAATACCG
Sequence	AGCCAGACGCCAGATTCCGTGGAAACTGGGTTTGCAGATTTTGAAGATAGTCATGGTC
	ACCACACAGCTTGTTCGTTTTGGTTTAAGTAACCAGCTGGTGGTTGCTTTCAAAGAAG
	ATAACACTGTTGCTTTTAAGCACTTGTTTTTGAAAGGATATTCTGGTACAGATGAAGA
	TGACTACAGCTGCAGTGTATATACTCAAGAGGATGCCTATGAGAGCATCTTTTTTGCT
	ATTAATCAGTATCATCAGCTAAAGGACATTACCCTGGGGACCCTTGGTTATGGAGAAA
	ATGAAGACAATAGAATTGGCTTAAAAGTCTGTAAGCAGCATTACAAGAAAGGGACCAT
	GTTTCCTTCTAATGAGACACTGAATATTGACAACGACGTTGAGCTAGATTGTGTTCAA
	TTAGACCTTCAGGACCTCTCCAAGAAGCCTCCGGACTGGAAGAACTCATCATTCTTCA
	GACTGGAATTTTATCGGCTCTTACAGGTTGAAATCTCCTTTCATCTTAAAGGCATTGA
	CCTACAGACAATTCATTCCCGTGAGTTACCAGACTGTTATGTCTTTCAGAATACGATT
	ATCTTTGACAATAAAGCTCACAGTGGCAAAATCAAAATCTATTTTGACAGTGATGCCA
	AAATTGAAGAATGTAAAGACTTGAACATATTTGGATCAGCTCAGAAAAATCCTCAGTA
	TGTCCTGGTGTTTGATGCATTTGTCATTGTGATTTGCTTGGCATCTCTTATTCTGTGT
	ACAAGATCCATTGTTCTTGCTCTAAGGTTACGGAAGAGATTTCTAAATTTCTTCCTGG
	AGAAGTACAAGCGGCCTGTGTGTGACACCGACCAGTGGGAGTTCATCAACGGCTGGTA
	TGTCCTGGTGATTATCAGCGACCTAATGACAATCATTGGCTCCATATTAAAAATGGAA
	ATCAAAGCAAAGAATCTCACAAACTATGATCTCTGCAGCATTTTTCTTGGAACCTCTA
	CGCTCTTGGTTTGGGTTGGAGTCATCAGATACCTGGGTTATTTCCAGGCATATAATGT
	ACTGATTTTAACAATGCAGGCCTCACTGCCAAAAGTTCTTCGGTTTTGTGCTTGTGCT
	GGTATGATTTATCTGGGTTACACATTCTGTGGCTGGATTGTCTTAGGACCATACCATG
	ACAAGTTTGAAAATCTGAACACAGTTGCTGAGTGTCTGTTTTCTCTGGTCAACGGTGA
	TGACATGTTTGCAACCTTTGCCCAAATCCAGCAGAAGAGCATCTTGGTGTGGCTQTTC
	AGTCGTCTGTATTTATATTCCTTCATCAGCCTTTTTATATATATGATTCTCAGTCTTT
	TTATTGCACTTATTACAGATTCTTATGACACCATTAAGAAATTCCAACAGAATGGGTT
	TCCTGAAACGGATTTGCAGGAATTCCTGAAGGAATGCAGTAGCAAAGAAGAGTATCAG
	AAAGAGTCCTCAGCCTTCCTGTCCTGCATCTGCTGTCGGAGGAGGAAAAGAAGTGATG
	ATCACTTGATACCTATTAGCTAAAGTTCTGCTAAAGATGATTAAAGTTCAGGCATCCT
	TATCCAGCAGCTGAGCAGAGGAACCCCAAATGACTTGGACAAGCAGTTCCAAAATGAC
	TCTCTTATTTAATGTGGAGTGGCAAAGAGCACTCACAGTTAGCCAGCTGACCATGACT
	GAAGTTCCAGCTTTACTTGTTATAAAACTTGAATGATAAAGAATAGACCATGGGCTAC
	TACTGCGCATTAGTGCAATATAACCAGCCGATAATAAAATTTCTCTATTAGTCTGTTA
	CTTTATGACATGATCTCGGAATGGCAAAGATTCATTTCCAGAAGTGTGCGAAATAATA
	GTTCTTACCCTGTTAATTACACATTGTGCGTCCTCGGCCCCAAGGGACTGGCACAAAG
	GGAACTGCGGTGGAAAACATTTGTTAATACCGGGCTCGGTCACAAAAGACCCGGTGGG
	GCATCCATTTAAGAGTCACGGGCGAACTACACGGGCAAGACC
	ORF Start: ATG at 31	ORF Stop: TAA at 1645
	SEQ ID NO:26	538 aa	MW at 62653.9 kD
NOV9c,	MAHRDSEMKEECLREDLKFYFMSPCEKYRARRQIPWKLGLQILKIVMVTTQLVRFGLS
CG90709-03	NQLVVAFKEDNTVAFKHLFLKGYSGTDEDDYSCSVYTQEDAYESIFFAINQYHQLKDI
Protein Sequence	TLGTLGYGENEDNRIGLKVCKQHYKKGTMFPSNETLNIDNDVELDCVQLDLQDLSKKP
	PDWKNSSFFRLEFYRLLQVEISFHLKGIDLQTIHSRELPDCYVFQNTIIFDNKAHSGK
	IKIYFDSDAKIEECKDLNIFGSAQKNAQYVLVFDAFVIVICLASLILCTRSIVLALRL
	RKRFLNFFLEKYKRPVCDTDQWEFINGWYVLVIISDLMTIIGSILKMEIKAKNLTNYD
	LCSIFLGTSTLLVWVGVIRYLGYFQAYNVLILTMQASLPKVLRFCACAGMIYLGYTFC
	GWIVLGPYHDKFENLNTVAECLFSLVNGDDMFATFAQIQQKSILVWLFSRLYLYSFIS
	LFIYMILSLFIALITDSYDTIKKFQQNGFPETDLQEFLKECSSKEEYQKESSAFLSCI
	CCRRRKRSDDHLIPIS
	SEQ ID NO:27	2067 bp
NOV9d,	ACGCGTTACGGGGAGGGGCGAAATGAGTCGGCCGTGAACGGTGTTTCCTGTTCCGAAT
CG90709-04 DNA	CCCGAGACCCCTGGAAAGTTTTGAAGGAGGAGGCATGGCCCGGCAGCCTTATCGTTTT
Sequence	CCCCAGCCAAGGATTCCCGAGAGAGGATCAGGTGTTTTCAGGTTAACCGTCACAAATG
	CAATGGCACATCGTGATTCTGAGATGAAAGAAGAATGTCTAAGGGAAGACCTGAAGTT
	TTACTGCATGAGCCCTTGTGAAAAATACCGAGCCAGACGCCAGATTCCGTGGAAACTG
	GGTTTGCAGATTTTGAAGATAGTCATGGTCACCACACAGCTTGTTCGTTTTGGTTTAA
	GTAACCACCTGGTGGTTGCTTTCAAAGAAGATAACACTGTTGCTTTTAAGCACTTCTT
	TTTGAAAGGATATTCTGGTACAGATGAAGATGACTACAGCTGCAGTGTATATACTCAA
	GAGGATGCCTATGAGAGCATCTTTTTTGCTATTIAATCAGTATCATCAGCTAAAGGACA
	TTACCCTGGGGACCCTTGGTTATGGAGAAAATGAAGACAATAGAATTGGCTTAAAAGT
	CTGTAAGCAGCATTACAAGAAAGGGACCATGTTTCCTTCTAATCAGACACTGAATATT
	GACAACGACGTTGAGCTAGATTGTGTTCAATTAGACCTTCAGGACCTCTCCAAGAAGC
	CTCCGGACTGGAAGAACTCATCATTCTTCAGACTGGAATTTTATCGGCTCTTACAGGT
	TGAAATCTCCTTTCATCTTAAAGGCATTGACCTACAGACAATTCATTCCCGTGAGTTA
	CCAGACTGTTATGTCTTTCAGAATACGATTATCTTTGACAATAAAGCTCACAGTGGCA
	AAATCAAAATCTATTTTGACAGTGATGCCAAAATTGAAGAATGTAAACACTTCAACAT
	ATTTGGATCAGCTCAGAAAAATGCTCAGTATGTCCTGGTGTTTGATGCATTTGTCATT
	GTGATTTGCTTGGCATCTCTTATTCTGTGTACAAGATCCATTGTTCTTGCTCTAAGGT
	TACGGAAGAGATTTCTAAATTTCTTCCTGGAGAAGTACAAGCGGCCTGTGTGTGACAC
	CGACCAGTGCGAGTTCATCAACGGCTGGTATGTCCTGGTGATTATCACCGACCTAATG
	ACAATCATTGGCTCCATATTAAAAATGGAAATCAAAGCAAAGAATCTCACAAACTATG
	ATCTCTGCAGCATTTTTCTTGGAACCTCTACGCTCTTGGTTTGGGTTGGAGTCATCAG
	ATACCTGGGTTATTTCCAGGCATATAATGTACTGATTTTAACAATGCAGGCCTCACTG
	CCAAAAGTTCTTCGGTTTTGTGCTTGTGCTGGTATGATTTATCTGGGTTACACATTCT
	GTGGCTGGATTGTCTTAGGACCATACCATGACAAGTTTGAAAATCTGAACACAGTTGC
	TGAGTGTCTGTTTTCTCTGGTCAACGGTGATGACATGTTTGCAACCTTTGCCCAAATC
	CAGCAGAAGAGCATCTTGGTGTGGCTGTTCAGTCGTCTGTATTTATATTCCTTCATCA
	GCCTTTTTATATATATGATTCTCAGTCTTTTTATTGCACTTATTACAGATTCTTATGA
	CACCATTAAGAAATTCCAACAGAATGGGTTTCCTGAAACGGATTTGCAGGAATTCCTG
	AAGGAATGCAGTAGCAAAGAAGAGTATCAGAAAGAGTCCTCAGCCTTCCTGTCCTGCA
	TCTGCTGTCGGAGGAGGAAAAGAAGTGATGATCACTTGATACCTATTAGCTAAAGTTC
	TGCTAAAGATGATTAAAGTTCAGGCATCCTTATCCAGCAGCTGAGCAGAGGAACCCCA
	AATGACTTGGACAAGCAGTTCCAIAAATGACTCTCTTATTTAATTGTGGAGTGGGAAAG
	AGGACTCACAGTTAGCCAGCTGACCATGACTGAAGTTCCAGCTTTACTTTTTATAAAC
	TTGAATGATAAAGAATAGACCATGGGCTACTACTGGGCATTAGTGCAATATAACAGCG
	ATAATAAAATTCTCTATTAGTCTGTTAATTTATGAAA
	ORF Start: ATG at 93	ORF Stop: TAA at 1791
	SEQ ID NO:28	566 aa MW at 65866.6 kD
NOV9d,	MARQPYRFPQARIPERGSGVFRLTVRNAMAHRDSEMKEECLREDLKFYCMSPCEKRYA
CG90709-04	RRQIPWKLGLQILKIVMVTTQLVRFGLSNQLVVAFKEDNTVAFKHLFLKGYSGTDEDD
Protein Sequence	YSCSVYTQEDAYESIFFAINQYHQLKDITLGTLGYGENEDNRIGLKVCKQHYKKGTMF
	PSNETLNIDNDVELDCVQLDLQDLSKKPPDWKNSSFFRLEFYRLLQVEISFHLKGIDL
	QTIHSRELPDCYVFQNTIIFDNKAHSGKIKIYFDSDAKIEECKDLNIFGSAQKNAQYV
	LVFDAFVIVICLASLILCTRSIVLALRLRKRFLNFFLEKYKRPVCDTDQWEFINGWYV
	LVIISDLMTIIGSILKMEIKAKNLTNYDLCSIFLGTSTLLVWVGVIRYLGYFQAYNVL
	ILTMQASLPKVLRFCACAGMIYLGYTFCGWIVLGPYHDKFENLNTVAECLFSLVNGDD
	MFATFAQIQQKSILVWLFSRLYLYSFISLFIYMILSLFIALITDSYDTIKKFQQNGFP
	ETDLQEFLKECSSKEEYQKESSAFLSCICCRRRKRSDDHLIPIS

[0313] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 9B.

TABLE 9B
Comparison of NOV9a against NOV9b through NOV9d.
		Identities/
	NOV9a Residues/	Similarities for the
Protein Sequence	Match Residues	Matched Region
NOV9b	1 . . . 540	485/545 (88%)
	1 . . . 544	493/545 (89%)
NOV9c	1 . . . 526	481/531 (90%)
	1 . . . 530	489/531 (91%)
NOV9d	1 . . . 526	480/531 (90%)
	29 . . . 558	488/531 (91%)

[0314] Further analysis of the NOV9a protein yielded the following properties shown in Table 9C.

TABLE 9C
Protein Sequence Properties NOV9a
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 65 and 66
analysis:

[0315] 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
			Identities/
			Similarities
			for the
Geneseq	Protein/Organism/Length	NOV9a Residues/	Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAM51858	Human TRP-like calcium	9 . . . 533	262/550 (47%)	e−142
	channel TLCC-2 - Homo	37 . . . 579	374/550 (67%)
	sapiens, 580 aa.
	[WO200177331-A1, 18-OCT-
	2001]
AAB74707	Human membrane associated	9 . . . 533	262/550 (47%)	e−142
	protein MEMAP-13 - Homo	37 . . . 579	374/550 (67%)
	sapiens, 580 aa.
	[WO200112662-A2, 22-FEB-
	2001]
AAB93412	Human protein sequence SEQ	109 . . . 523	241/426 (56%)	e−139
	ID NO:12616 - Homo sapiens,	76 . . . 497	318/426 (74%)
	497 aa. [EP1074617-A2, 07-
	FEB-2001]
AAB08906	Human secreted protein	42 . . . 533	244/517 (47%)	e−131
	sequence encoded by gene 16	1 . . . 510	349/517 (67%)
	SEQ ID NO:63 - Homo sapiens,
	511 aa. [WO200017222-A1, 30-
	MAR-2000]
ABB11279	Human secreted protein	334 . . . 497	161/164 (98%)	3e−90
	homologue, SEQ ID NO:1649 -	1 . . . 164	163/164 (99%)
	Homo sapiens, 164 aa.
	[WO200157188-A2, 09-AUG-
	2001]

[0316] 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
Q9CQD3	3300002C04RIK PROTEIN -	1 . . . 523	426/528 (80%)	0.0
	Mus musculus (Mouse), 538 aa.	1 . . . 527	466/528 (87%)
AAL84622	MUCOLIPIN-3 - Homo sapiens	10 . . . 523	304/525 (57%)	e−177
	(Human), 553 aa.	35 . . . 553	396/525 (74%)
AAL84623	MUCOLIPIN-3 - Mus musculus	3 . . . 523	306/534 (57%)	e−176
	(Mouse), 553 aa.	23 . . . 553	398/534 (74%)
Q9H4B3	MUCOLIPIDIN - Homo sapiens	9 . . . 533	262/550 (47%)	e−142
	(Human), 580 aa.	37 . . . 579	374/550 (67%)
Q9GZU1	CDNA: FLJ22449 FIS, CLONE	9 . . . 533	262/550 (47%)	e−142
	HRC09609 (MUCOLIPIN)	37 . . . 579	374/550 (67%)
	(MUCOLIPIDOSIS TYPE IV
	PROTEIN) (MUCOLIPIN 1) -
	Homo sapiens (Human), 580 aa.

[0317] PFam analysis indicates that the NOV9a protein contains the domains shown in Table 9F.

TABLE 9F
Domain Analysis of NOV9a
		Identities/
		Similarities
Pfam Domain	NOV9a Match Region	for the Matched Region	Expect Value
DUF214: domain 1 of 1	231 . . . 407	30/267 (11%)	9.2
		117/267 (44%)
ion_trans: domain 1 of 1	314 . . . 474	31/236 (13%)	0.01
		117/236 (50%)

Example 10

[0318] 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:29         642 bp
NOV 10a,          CACCAAGGGCCTGGCACCAGGTGCCCAGTCTTCCAGTTGCGAGGGCAAGCAAACCCGT
CG90739-01 DNA    CATGAGCAACTCCCTTCCCCATCTCTGCTCACCATGTGGACGCTGAAATCGTCCCTGG
Sequence          TCCTGCTTCTGTGCCTCACCTGCAGCTATGCCTTTATGTTCTCTTCTCTGAGACAGAA
                  AACTAGCGAACCCCAGGGGAAGGTGCCGTGTGGAGACCACTTTCGGATTCGGCAGAAC
                  CTACCAGAGCACACCCAAGGCTGGCTTGGGAGCAAATGGCTCTGGCTTTTGTTTGCTG
                  TTGTGCCGTTTGTGATACTGCAGTGTCAAAGAGACAGTGAGAAGAATAAGGAGCAGAG
                  TCCTCCTGGCCTTCGAGGCTTCCCATTTCGCACTCCACTAAAGAAAAATCAAAATGCT
                  TCTCTTTACAAAGACTGTGTATTCAATACCTTAAACGAACTTGAAGTGGAGCTTTTGA
                  AATTTGTGTCCGAAGTGCAGAATCTTAAAGGTGCCATGGCAACAGGCAGTGGCAGTAA
                  CCTCAAGCTTCGAAGGTCAGAGATGCCTGCAGATCCATACCATGTCACAATCTGTAAA
                  ATATGGGGAGAAGAAAGCTCTAGCTGAATGGATTTGTGTGTCAGGAGAGAAAAAAGTT
                  GAGT
                  ORF Start: ATG at 92 ORF Stop: TGA at 605
                  SEQ ID NO:30         171 aa MW at 19498.4 kD
NOV10a,           MWTLKSSLVLLLCLTCSYAFMFSSLRQKTSEPQGKVPCGEHFRIRQNLPEHTQGWLGS
CG90739-01        KWLWLLFAVVPFVILQCQRDSEKNKEQSPPGLRGFPFRTPLKKNQNASLYKDCVFNTL
Protein Sequence  NELEVELLKFVSEVQNLKGAMATGSGSNLKLRRSEMPADPYHVTICKIWGEESSS
                  SEQ ID NO:31         141 bp
NOV 10b,          GGATCCTTTATGTTCTCTTCTCTGAGACAGAAAACTAGCGAACCCCAGGGGAAGGTGC
172390256 DNA     CGTGTGGAGAGCACTTTCGGATTCGGCAGAACCTACCAGAGCACACCCAAGGCTGGCT
Sequence          TGGGAGCAAATGGCTCTGGCTCGAG
                  ORF Start: at 1      ORF Stop: end of sequence
                  SEQ ID NO:32         47 aa MW at 5515.2 kD
NOV 10b,          GSFMFSSLRQKTSEPQGKVPCGEHFRIRQNLPEHTQGWLGSKWLWLE
172390256 Protein
Sequence
                  SEQ ID NO:33         141 bp
NOV 10c,          GGATCCTTTATGTTCTCTTCTCTGAGACAGAAAACTAGCGAACCCCAGGGGAAGGTGC
172390440 DNA     AATACGGAGAGCACTTTCGGATTCGGCAGAATCTACCAGAGCACACCCAAGGCTGGCT
Sequence          TGGGAGCAA.ATGGCTCTGGCTCGAG
                  ORF Start: at 1      ORF Stop: end of sequence
                  SEQ ID NO:34         47 aa MW at 5606.3 kD
NOV 10c,          GSFMFSSLRQKTSEPQGKVQYGEHFRIRQNLPEHTQGWLGSKWLWLE
172390440 Protein
Sequence
                  SEQ ID NO:35         468 bp
NOV 10d,          GGATCCTTTATGTTCTCTTCTCTGAGACAGAAAACTAGCGAACCCCAGGGGAAGGTGC
172390569 DNA     CGTGTGGAGAGCACTTTCGGATTCGGCAGAACCTACCAGAGCACACCCAAGGCTGGCT
Sequence          TGGGAGCAAATGGCTCTGGCTTTTGTTTGCTGTTGTGCCGTTTGTGATACTGAAGTGT
                  CAAAGAGACAGTGAGAAGAATAAGGAGCAGAGTCCTCCTGGCCTTCGAGGCTTCCCAT
                  TTCGCACTCCACTAAAGAAAAATCAAAATGCTTCTCTTTACAAAGACTGTGTATTCAA
                  TACCTTAAACGAACTTGAAGTGGAGCTTTTGAAATTTGTGTCCGAAGTGCAGAATCTT
                  AAAGGTGCCATGGCAACAGGCAGTGGCAGTAACCTCAAGCTTCGAAGGTCAGAGATGC
                  CTGCAGATCCATACCATGTCACAATCTGTAAAATATGGGGAGAAGAAAGCTCTAGCCT
                  CGAG
                  ORF Start: at 1      ORF Stop: end of sequence
                  SEQ ID NO:36         156 aa MW at 17757.3 kD
NOV 10d,          GSFMFSSLRQKRSEPQGKVPCGEHFRIRQNLPEHTQGWLFSKWLWLLFAVVPFVILKC
172390569 Protein QRDSEKNKEQSPPGLRGFPFRTPLKKNQNASLYKDCVFNTLNELEVELLKFVSEVQNL
Sequence          KGAMATGSGSNLKLRRSEMPADPYHVTICKIWGEESSSLE
                  SEQ ID NO:37         468 bp
NOV 10c,          GGATCCTTTATGTTCTCTTCTCTGAGACAGAAAACTAGCGAACCCCAGGGGAAGGTGC
172390587 DNA     CGTGTGGAGAGCACTTTCGGATTCGGCAGAACCTACCAGAGCACACCCAAGGCTGGCT
Sequence          TGGGAGCAAATGGCTCTGGCTTTTGTTTGCTGTTGTGCCGTTTGTGATACTGCAGTGT
                  CAAAGAGACAGTGAGAAGAATAAGGAGCAGAGTCCTCCTGGCCTTCGAGGCTTCCCAT
                  TTCGCACTCCACTAAAGAAAAATCAAAATGCTTCTCTTTACAAAGACTGTGTATTCAA
                  TACCTTAAACGAACTTGAAGTGGAGCTTTTGAAATTTGTGTCCGAAGTGCAGAATCTT
                  AAAGGTGCCATGGCAACAGGCAGTGCCAGTAACCTCAAGCTTCGAAGGTCAGAGATGC
                  CTGCAGATCCATACCATGTCACAATCTGTAAAATATGGGGAGAAGAAAGCTCTAGCCT
                  CGAG
                  ORF Start: at 1      ORF Stop: end of sequence
                  SEQ ID NO:38         156 aa MW at 17757.2 kD
NOV 10e,          GSFMFSSLRQKTSEPQGKVPCGEHFRIRQNLPEHTQGWLGSKWLWLLFAVVPFVILQC
172390587 Protein QRDSEKNKEQSPPFLRGRPFRTPLKKNQNASLYKDCVFNTLNELEVELLKFVSEVQNL
Sequence          KGAMATGSGSNLKLRRSEMPADPYHVTICKIWGEESSSLE
                  SEQ ID NO:39         468 bp
NOV 10f           GGATCCTTTATGTTCTCTTCTCTGAGACAGAJAAACTAGCGAACCCCAGGGGAAGGTGC
172390603 DNA     CGTGTGGAGAGCACTTTCGGATTCGGCAGAACCTACCAGAGCACACCCAAGGCTGGCT
Sequence          TGGGAGCAAATGGCTCTGGCTTTTGTTTGCTGTTGTGCCCTTTGTGATACTGAAGTGT
                  CAAAGAGACAGTGAGAAGAATAAGGAGCAGAGTCCTCCTGGCCTTCGAGGCTTCCCAT
                  TTCGCACTCCACTAAAGAAAAATCAAAATGCTTCTCTTTACAAAGACTGTGTATTCAA
                  TACCTTAAACGAACTTGAAGTGGAGCTTTTGAAATTTGTGTCCGAAGTGCAGAACCTT
                  AAAGGTGCCATGGCAACAGGCAGTGGCAGTAACCTCAAGCTTCGAAGGTCAGAGATGC
                  CTCCAGATCCATACCATGTCACAATCTGTAAAATATGGGGACAAGAAAGCTCTAGCCT
                  CGAG
                  ORF Start: at 1      ORF Stop: end of sequence
                  SEQ ID NO:40         156 aa MW at 17757.3 kD
NOV 10f,          GSFMFSSLRQKTSEPQGKVPCGEHFRIRQNLPEHTQGWLGSKWLWLLFAVVPFVILKC
172390603 Protein QRDSEKNKEQSPPGLRGFPFRTPLKKNQNASLYKDCVFNTLNELEVELLKFVSEVQNL
Sequence          KGAMATGSGSNLKLRRSEMPADPYHVTICKIWGEESSSLE
                  SEQ ID NO:41         468 bp
NOV 10g,          GGATCCTTTATGTTCTCTTCTCTGAGACAGAAAACTAGCGAACCCCAGGGGAAGGTGC
172390624 DNA     CGTGTGGAGAGCACTTTCGGATTCGGCAGAACCTACCAGAGCACACCCAAGGCTGGCT
Sequence          TGGGAGCAAATGGCTCTGGCTTTTGTTTGCTGTTGTGCCGTTTGTGATACTGAAGTGT
                  CAAAGAGACAGTGAGAAGAATAAGGAGCAGAGTCCTCCTGGCCTTCGAGGCTTCCCAT
                  TTCGCATTCCACTAAAGAAAAATCAAAATGCTTCTCTTTACAAAGACTGTGTATTCAA
                  TACCTTAAACGAACTTGAAGTGGAGCTTTTGAAATTTGTGTCCGAAGTGCAAAATCTT
                  AAAGGTGCCATGGCAACAGGCAGTGGCAGTAACCTCAAGCTTCGAAGGTCAGAGATGC
                  CTGCAGATCCATACCATGTCACAATCTGTAAAATATGGGGAGAAGAAAGCTCTAGCCT
                  CGAG
                  ORF Start: at 1      ORF Stop: end of sequence
                  SEQ ID NO:42         156 aa MW at 17769.3 kD
NOV 10g,          GSFMFSSLRQKTSEPQFKVPCGEHFRIRQNLPEHTQGWLGSKWLWLLFAVVPFVILKC
172390624 Protein QRDSEKNKEQSPPGLRGFPFRIPLKKNQNASLYKDCVFNTLNELEVELLKFVSEVQNL
Sequence          KGAMATGSGSNLKLRRSEMPADPYHVTICKIWGEESSSLE
                  SEQ ID NO:43         468 bp
NOV 10h,          GGATCCTTTATGTTCTCTTCTCTGAGACAGAAAACTAGCGAACCCCAGGGGAAGGTGC
172390644 DNA     AATACGGAGAGCACTTTCGGATTCGGCAGAACCTACCAGAGCACACCCAAGGCTGGCT
Sequence          TGGGAGCAAATGGCTCTGGCTTTTGTTTGCTGTTGTGCCGTTTGTGATACTGAAGTGI
                  CAAAGAGACAGTGAGAAGAATAAGGAGCAGAGTCCTCCTGGCCTTCGAGGCTTCCCAT
                  TTCGCACTCCACTAAAGAAAAATCAAAATGCTTCTCTTTACAAAGACTGTGTATTCAA
                  TACCTTAAACGAACTTGAAGTGGAGCTTTTGAAATTTGTGTCCGAAGTGCAAAATCTT
                  AAAGGTGCCATGGCAACAGGCAGTGGCAGTAACCTCAAGCTTCGAAGGTCAGAGATGC
                  CTGCAGATCCATACCATGTCACAATCTGTAAAATATGGGGAGAAGAAAGCTCTAGCCT
                  CGAG
                  ORF Start: at 1      ORF Stop: end of sequence
                  SEQ ID NO:44         156 aa MW at 17848.3 kD
NOV 10h,          GSFMFSSLRQKTSEPQGKVQYGEHFRIRQNLPEHTQGWLGSKWLWLLFAVVPFVILKC
172390644 Protein QRDSEKNKEQSPPGLRGFPFRTPLKKNQNASLYKDCVFNTLNELEVELLKFVSEVQNL
Sequence          KGAMATGSGSNLKLRRSEMPADPUHVTICKIWGEESSSLE

[0319] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 10B.

TABLE 10B
Comparison of NOV10a against NOV10b through NOV10h.
		Identities/
	NOV10a Residues/	Similarities for the
Protein Sequence	Match Residues	Matched Region
NOV10b	19 . . . 63	44/45 (97%)
	2 . . . 46	45/45 (99%)
NOV10c	19 . . . 63	42/45 (93%)
	2 . . . 46	43/45 (95%)
NOV10d	19 . . . 171	151/153 (98%)
	2 . . . 154	153/153 (99%)
NOV10e	19 . . . 171	152/153 (99%)
	2 . . . 154	153/153 (99%)
NOV10f	19 . . . 171	151/153 (98%)
	2 . . . 154	153/153 (99%)
NOV10g	19 . . . 171	150/153 (98%)
	2 . . . 154	152/153 (99%)
NOV10h	19 . . . 171	149/153 (97%)
	2 . . . 154	151/153 (98%)

[0320] Further analysis of the NOV10a protein yielded the following properties shown in Table 10C.

TABLE 10C
Protein Sequence Properties NOV10a
PSort     0.4600 probability located in plasma membrane; 0.1031 probability located in
analysis: microbody (peroxisome); 0.1000 probability located in endoplasmic reticulum
          (membrane); 0.1000 probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 20 and 21
analysis:

[0321] 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 10D.

TABLE 10D
Geneseq Results for NOV10a
		NOV10a	Identifies/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAU68550	Human novel cytokine encoded	1 . . . 171	150/171 (87%)	5e−85
	by cDNA 790CIP2D_11 #1 -	69 . . . 239	158/171 (91%)
	Homo sapiens, 239 aa.
	[WO200175093-A1,
	11-OCT-2001]
AAY53032	Human secreted protein clone	1 . . . 171	150/171 (87%)	5e−85
	di393_2 protein sequence SEQ	1 . . . 171	158/171 (91%)
	ID NO: 70 - Homo sapiens,
	171 aa. [WO9957132-A1,
	11-NOV-1999]
AAG00463	Human secreted protein, SEQ	1 . . . 101	92/101 (91%)	2e−49
	ID NO: 4544 - Homo sapiens,	1 . . . 101	93/101 (91%)
	101 aa. [EP1033401-A2,
	06-SEP-2000]
AAY12683	Human 5′ EST secreted protein	1 . . . 101	92/101 (91%)	2e−49
	SEQ IDNO: 273 -	1 . . . 101	93/101 (91%)
	Homo sapiens, 101 aa.
	[WO9906549-
	A2, 11-FEB-1999]
AAM87953	Human immune/haematopoietic	83 . . . 171	70/89 (78%)	1e−34
	antigen SEQ ID NO: 15546 -	1 . . . 89	79/89 (88%)
	Homo sapiens, 89 aa.
	[WO200157182-A2,
	09-AUG-2001]

[0322] 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 10E.

TABLE 10E
Public BLASTP Results for NOV10a
		NOV10a	Identifies/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9HCV6	DJ1153D9.4 (NOVEL PROTEIN) -	34 . . . 171	138/138 (100%)	7e−79
	Homo sapiens (Human), 138 aa	1 . . . 138	138/138 (100%)
	(fragment).
Q9D9T2	1700029J11RIK PROTEIN - Mus	4 . . . 170	99/168 (58%)	2e−46
	musculus (Mouse), 170 aa.	5 . . . 169	122/168 (71%)
Q96C09	SIMILAR TO NEURONAL	1 . . . 88	83/88 (94%)	9e−45
	THREAD PROTEIN -	1 . . . 88	85/88 (96%)
	Homo sapiens (Human), 106 aa.
Q9HCV7	DJ1153D9.3 (NOVEL PROTEIN) -	1 . . . 86	81/86 (94%)	4e−42
	Homo sapiens (Human), 94 aa.	1 . . . 86	81/86 (94%)
Q9CRL6	2810426N06RIK PROTEIN - Mus	13 . . . 51	17/45 (37%)	4.4
	musculus (Mouse), 300 aa	188 . . . 232	24/45 (52%)
	(fragment).

[0323] No significant matches were found in a PFam analysis of the NOV 10a protein.

Example 11

[0324] 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:45	1152 bp
NOV11a,	ATGACCGCGACCGAAGCCCTCCTGCGCGTCCTCTTGCTCCTGCTGGCTTTCGGCCACA
CG91667-01 DNA	GCACCTATGGGGCTGAATGCTTCCCGGCCTGCAACCCCCAAAATGGATTCTGCGAGGA
Sequence	TGACAATGTTTGCAGGTGCCATGTCGGCTGGCAGGGTCCCCTTTGTGACCAGTGCGTG
	ACCTCTCCCGGCTGCCTTCACGGACTCTCTGGAGAACCCGGGCAGTGCATTTGCACCG
	ACGGCTGGGACGGGGAGCTCTGTGATAGAGATGTTCGGGCCTGCTCCTCGGCCCCCTG
	TGCCAACAACGGGACCTGCGTGAGCCTGGACGGTGGCCTCTATGAATGCTCCTGTGCC
	CCCGGGTACTCGGGAAAGGACTGCCAGAAAAAGGACGGGCCCTGTGTGATCAACGGCT
	CCCCCTGCCAGCACGGAGGCACCTGCGTGGATGATGAGGGCCCGCCCTCCCATGCCTC
	CTGCCTGTGCCCCCCTGGCTTCTCAGGCAATTTCTGCGAGATCGTGGCCAACAGCTGC
	ACCCCCAACCCATGCGAGAACGACGGCGTCTGCACTGACATTGGGGGCGACTTCCGCT
	GCCGGTGCCCAGCCGGCTTCATCGACAAGACCTGCAGCCGCCCGGTGACCAACTGCGC
	CAGCAGCCCGTGCCAGAACGGGGGCACCTGCCTGCAGCACACCCAGGTGAGCTACGAG
	TGTCTGTGCAAGCCCGAGTTCACAGGTCTCACCTGTGTCAAGAAGCGCGCGCTGAGCC
	CCCAGCAGGTCACCCGTCTGCCCAGCGGCTATGGGCTGGCCTACCGCCTGACCCCTGG
	GGTGCACGAGCTGCCGGTGCAGCAGCCGGAGCACCGCATCCTGAAGGTGTCCATGAAA
	GAGCTCAACAAGAAAACCCCTCTCCTCACCGAGGGCCAGGCCATCTGCTTCACCATCC
	TGGGCGTGCTCACCAGCCTGGTGGTGCTGGGCACTGTGGGTATCGTCTTCCTCAACAA
	GTGCGAGACCTGGGTGTCCAACCTGCGCTACAACCACATGCTGCGGAAGAAGAAGAAC
	CTGCTGCTTCAGTACAACAGCGGGGAGGACCTGGCCGTCAACATCATCTTCCCCGAGA
	AGATCGACATGACCACCTTCAGCAAGGAGGCCGGCGACGAGGAGATCTAA
	ORF Start: ATG at 1	ORF Stop: TAA at 1150
	SEQ ID NO:46	383 aa	MW at 41153.6kD
NOV11a,	MTATEALLRVLLLLLAFGHSTYGAECFPACNPQNGFCEDDNVCRCHVGWQGPLCDQCV
CG91667-01	TSPGCLHGLCGEPGQCICTDGWDGELCDRDVRACSSAPCANNGTCVSLDGGLYECSCA
Protein Sequence	PGYSGKDCQKKDGPCVINGSPCQHGGTCVDDEGRASHASCLCPPGFSGNFCEIVANSC
	TPNPCENDGVCTDIGGDFRCRCPAGFIDKTCSRPVTNCASSPCQNGGTCLQHTQVSYE
	CLCKPEFTGLTCVKKRALSPQQVTRLPSGYGLAYRLTPGVHELPVQQPEHRILKVSMK
	ELNKKTPLLTEGQAICFTILGVLTSLVVLGTVGIVFLNKCETWVSNLRYNHMLRKKKN
	LLLQYNSGEDLAVNIIEFPEKIDMTTFSKEAGDEEI
	SEQ ID NO:47	1299bp
NOV11b,	TCCGCAACCAGAAGCCCAGTGCGGCGCCAGGAGCCGGACCCGCGCCCGCACCGCTCCC
CG91667-02 DNA	GGGACCGCGACCCCGGCCGCCCAGAGATGACCGCGACCGAAGCCCTCCTGCGCGTCCT
Sequence	CTTGCTCCTGCTGGCTTTCGGCCACAGCACCTATGGGGCTGAATGCTTCCCGGCCTGC
	AACCCCCAAAATGGATTCTGCGAGGATGACAATGTTTGCAGGTGCCAGCCTGGCTGGC
	AGGGTCCCCTTTGTGACCAGTGCGTGACCTCTCCCGGCTGCCTTCACGGACTCTGTGG
	AGAACCCGGGCAGTGCATTTGCACCGACGGCTGGGACGGGGAGCTCTGTGATAGAGAT
	GTTCGGGCCTGCTCCTCGGCCCCCTGTGCCAACAACGGGACCTGCGTGAGCCTGGACG
	ATGGCCTCTATGAATGCTCCTGTGCCCCCGGGTACTCGGGAAAGGACTGCCAGAAAAA
	GGACGGGCCCTGTGTGATCAACGGCTCCCCCTGCCAGCACGGAGGCACCTGCGTGGAT
	GATGAGGGCCGGGCCTCCCATGCCTCCTGCCTGTGCCCCCCTGGCTTCTCAGGCAATT
	TCTGCGAGATCGTGGCCAACAGCTGCACCCCCAACCCATGCGAGAACGACGGCGTCTG
	CACTGACATCGGGGGCGACTTCCGCTGCCGGTGCCCAGCCGGCTTCATCGACAAGACC
	TGCAGCCGCCCGGTGACCAACTGCGCCACCAGCCCGTGCCAGAACGGGGGCACCTGCC
	TGCAGCACACCCAGGTGAGCTACGAGTGTCTGTGCAAGCCCGAGTTCACAGGTCTCAC
	CTGTGTCAAGAAGCGCGCGCTGAGCCCCCAGCAGGTCACCCGTCTGCCCAGCGGCTAT
	GGGCTGGCCTACCGCCTGACCCCTGGGGTGCACGAGCTGCCGGTGCAGCAGCCGGAGC
	ACCGCATCCTGAAGGTGTCCATGAAAGAGCTCAACAAGAAAACCCCTCTCCTCACCGA
	CGGCCAGGCCATCTGCTTCACCATCCTGGGCGTGCTCACCAGCCTGGTGGTGCTGGGC
	ACTGTGGGTATCGTCTTCCTCAACAAGTGCGAGACCTGGGTGTCCAACCTGCGCTACA
	ACCACATGCTGCGGAAGAAGAAGAACCTGCTGCTTCAGTACAACAGCGGGGAGGACCT
	GGCCGTCAACATCATCTTCCCCGAGAAGATCGACATGACCACCTTCAGCAAGGAGGCC
	GGCGACGAGGAGATCTAAGCAGCGTTCCCACAGCCCCCTCTAGATTCTTGGAGTTCCT
	CAGAGCTTACTATACGCGGTCTG
	ORF Start: ATG at 85	ORF Stop: TAA at 1234
	SEQ ID NO:48	383 aa	MW at 41200.6 kD
NOV11b,	MTATEALLRVLLLLLAFGHSTYGAECFPACNPQNGFCEDDNVCRCQPGWQGPLCDQCV
CG91667-02	TSPGCLHGLCGEPGQCICTDGWDGELCDRDVRACSSAPCANNGTCVSLDDGLYECSCA
Protein Sequence	PGYSGKDCQKKDGPCVINGSPCQHGGTCVDDEGRASHASCLCPPGFSGNFCEIVANSC
	TPNPCENDGVCTDIGGDFRCRCPAGFIDKTCSRPVTNCASSPCQNGGTCLQHTQVSYE
	CLCKPEFTGLTCVKKRALSPQQVTRLPSGYGLAYRLTPGVHELPVQQPEHRILKVSMK
	ELNKKTPLLTEGQAICFTILGVLTSLVVLGTVGIVFLNKCETWVSNLRYNHMLRKKKN
	LLLQYNSGEDLAVNIIFPEKIDMTTFSKEAGDEEI

[0325] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 11B.

TABLE 11B
Comparison of NOV11a against NOV11b.
	Protein	NOV11a Residues/	Identities/Similarities
	Sequence	Match Residues	for the Matched Region
	NOV11b	1 . . . 383	353/383 (92%)
		1 . . . 383	353/383 (92%)

[0326] Further analysis of the NOV11a protein yielded the following properties shown in Table 11C.

TABLE 11C
Protein Sequence Properties NOV11a
PSort     0.4600 probability located in plasma membrane; 0.1000 probability located in
analysis: endoplasmic reticulum (membrane); 0.1000 probability located in endoplasmic
          reticulum (lumen); 0.1000 probability located in outside
SignalP   Cleavage site between residues 24 and 25
analysis:

[0327] 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
			Identities/
			Similarities
		NOV11a	for the
Geneseq	Protein/Organism/Length	Residues/	Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAR56166	Neuroendocrine tumor dlk -	1 . . . 383	380/383 (99%)	0.0
	Homo sapiens, 383 aa.	1 . . . 383	380/383 (99%)
	[WO9413701-A, 23-JUN-1994]
AAR56167	Neuroendocrine tumor dlk - Mus	1 . . . 383	330/385 (85%)	0.0
	sp, 385 aa. [WO9413701-A, 23-	1 . . . 385	348/385 (89%)
	JUN-1994]
AAY77124	Human neurotransmission-	1 . . . 185	157/185 (84%)	2e−95
	associated protein (NTAP)	1 . . . 163	159/185 (85%)
	1296451 - Homo
	sapiens, 272 aa.
	[WO200001821-A2, 13-JAN-
	2000]
AAE13632	Human preadipocyte factor-1-	7 . . . 322	120/319 (37%)	1e−63
	like protein - Homo sapiens, 383	10 . . . 325	168/319 (52%)
	aa. [WO200157233-A2, 09-
	AUG -2001]
AAG67516	Amino acid sequence of	7 . . . 322	120/319 (37%)	2e−63
	a human secreted	10 . . . 325	167/319 (51%)
	polypeptide -
	Homo sapiens,
	383 aa. [WO200166690-
	A2, 13-SEP-2001]

[0328] In a BLAST search of public sequence datbases, the NOVI11a 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
P80370	Delta-like protein precursor (DLK)	1 . . . 383	381/383 (99%)	0.0
	(pG2) [Contains: Fetal antigen 1	1 . . . 383	381/383 (99%)
	(FA1)] - Homo sapiens (Human), 383 aa.
Q96DW5	UNKNOWN (PROTEIN FOR	1 . . . 383	380/383 (99%)	0.0
	MGC: 17291) - Homo sapiens	1 . . . 383	380/383 (99%)
	(Human), 383 aa.
Q969Y6	HYPOTHETICAL 41.2 KDA	1 . . . 383	379/383 (98%)	0.0
	PROTEIN (SIMILAR TO DELTA-	1 . . . 383	380/383 (98%)
	LIKE HOMOLOG) (DROSOPHILA) -
	Homo sapiens (Human), 383 aa.
Q925U3	DLK (DELTA LIKE) - Mus musculus	1 . . . 383	332/385 (86%)	0.0
	(Mouse), 385 aa.	1 . . . 385	350/385 (90%)
A54785	preadipocyte factor 1 precursor, long	1 . . . 383	331/385 (85%)	0.0
	form - mouse, 385 aa.	1 . . . 385	349/385 (89%)

[0329] PFam analysis indicates that the NOV11a protein contains the domains shown in Table 11F.

TABLE 11F
Domain Analysis of NOV11a
		Identities/
		Similarities
	NOV11a Match	for the	Expect
Pfam Domain	Region	Matched Region	Value
EGF: domain 1 of 6	26 . . . 54	10/47 (21%)	2.6
		20/47 (43%)
Bowman-Birk_leg:	70 . . . 85	8/22 (36%)	3.3
domain 1 of 1		13/22 (59%)
EGF: domain 2 of 6	57 . . . 85	9/47 (19%)	0.1
		21/47 (45%)
metalthio: domain	61 . . . 117	14/67 (21%)	5.9
1 of 1		33/67 (49%)
EGF: domain 3 of 6	92 . . . 124	19/47 (40%)	8.2e−09
		28/47 (60%)
EGF: domain 4 of 6	131 . . . 167	17/47 (36%)	5.4e−08
		28/47 (60%)
EGF: domain 5 of 6	174 . . . 205	15/47 (32%)	7.4e−09
		28/47 (60%)
EGF: domain 6 of 6	212 . . . 244	16/47 (34%)	1.2e−07
		25/47 (53%)
Keratin_B2:	134 . . . 253	29/183 (16%)	2.4
domain 1 of 1		58/183 (32%)

Example 12

[0330] 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:49	3121 bp
NOV12a,	AATTCGCATGGTCAACATGAAAAGTAAGGAACCTGCCGTGGGATCTAGATTCTTCTCT
CG92293-01 DNA	AGAATTAGTAGTTGGAGAAATTCAACAGTGACTGGACATCCATGGCAGGTCTCCCTAA
Sequence	AATCAGATGAGCACCACTTCTGTGGAGGAAGCTTGATTCAAGAAGATCGGGTTGTTAC
	TCTGGGGAGTACAGCCTCTTTCAGAAGGATAAGCAAGAACAGAATATTCCTGTCTCAA
	AAATTATTACCCATCCTGAATACAACAGCCGTGAATATATGAGTCCTGATATTGCACT
	GCTGTATCTAAAACACAAAGTCAAGTTTGGAAATGCTGTTCAGCCAATCTGTCTTCCT
	GACAGCGATGATAAAGTTGAACCAGGAATTCTTTGCTTATCCAGTGGATGGGGCAAGA
	TTTCCAAAACATCAGAATATTCAAATGTCCTACAAGAAATGGAACTTCCCATCATGGA
	TGACAGAGCGTGTAATACTGTGCTCAAGAGCATGAACCTCCCTCCCCTGGGAAGGACC
	ATGCTGTGTGCTGGCTTCCCTGATGGGGGAATGGACGCCTGCCAGGCGGACTCTGGAG
	GACCACTGGTTTGTAGAAGAGGTGGTGGAATCTGGATTCTTGCTGGGATAACTTCCTG
	GGTAGCTGGTTGTGCTGGAGGTTCAGTTCCCGTAAGAAACAACCATGTGAAGGCATCA
	CTTGGCATTTTCTCCAAAGTGTCTGAGTTGATGGATTTTATCACTCAAAACCTGTTCA
	CAGGTTCCATTTATTACATTTTCTTCACCTTCCCCTACCCCAGCTTATATGTTTGGAA
	AATAATGGTACCAGAAGATAAAATAATCCTGATAAAATTTACAAGTTTAGACATGGAA
	AAGCAAGTTGGATGTGATCATGACTATGTATCTTTACGATCAAGCAGTGGAGTGCTTT
	TTAGTAAGGTCTGTGGAAAAATATTGCCTTCACCATTGCTGGCAGAGACCAGTGAGGC
	CATGGTTCCATTTGTTTCTGATACAGAAGACAGTGGCAGTGGCTTTGAGCTTACCGTT
	ACTGCTGTACAGAAGTCAGAAGCAGGGTCAGGTTGTGGGAGTCTGGCTATATTGGTAG
	AAGAAGGGACAAATCACTCTGCCAAGTATCCTGATTTGTATCCCAGTAACACAAGGTG
	TCATTGGTTCATTTGTGCTCCAGAGAAGCACATTATAAAGTTGACATTTGAGGACTTT
	GCTGTCAAATTTAGTCCAAACTGTATTTATGATGCTGTTGTGATTTACGGTGATTCTG
	AAGAAAAGCACAAGTTAGCTAAACTTTGTGGAATGCTGACCATCACTTCAATATTCAG
	TTCTAGTAACATGACGGTGATATACTTTAAAAGTGATGGTAAAAATCGTTTACAAGGC
	TTCAAGGCCAGATTTACCATTTTGCCCTCAGAGTCTTTAAACAAATTTGAACCAAAGT
	TACCTCCCCAAAACAATCCTGTATCTACCGTAAAAGCTATTCTGCATGATGTCTGTGG
	CATCCCTCCATTTAGTCCCCAGTGGCTTTCCAGAAGAATCGCAGGAGGGGAAGAAGCC
	TGCCCCCACTGTTGGCCATGGCAGGTGGGTCTGAGGTTTCTAGGCGATTACCAATGTG
	GAGGTGCCATCATCAACCCAGTGTGGATTCTGACCGCAGCCCACTGTGTGCAATTGAA
	GAATAATCCACTCTCCTGGACTATTATTGCTGGGGACCATGACAGAAACCTGAAGGAA
	TCAACAGAGCAGGTGAGAAGGGCCAAACACATAATAGTGCATGAAGACTTTAACACAC
	TAAGTTATGACTCTGACATTGCCCTAATACAACTAAGCTCTCCTCTGGAGTACAACTC
	GGTGGTGAGGCCAGTATGTCTCCCACACAGCGCAGAGCCTCTATTTTCCTCGGAGATC
	TGTGCTGTGACCGGATGGGGAAGCATCAGTGCAGATGGTGGCCTAGCAAGTCGCCTAC
	AGCAGATTCAAGTGCATGTGTTAGAAAGAGAGGTCTGTGAACACACTTACTATTCTGC
	CCATCCAGGAGGGATCACAGAGAAGATGATCTGTGCTGGCTTTGCAGCATCTGGAGAG
	AAAGATTTCTGCCAGGGAGACTCTGGTGGGCCACTAGTATGTAGACATGAAAATGGTC
	CCTTTGTCCTCTATGGCATTGTCAGCTGGGGAGCTGGCTGTGTCCAGCCATGGAAGCC
	GGGTGTATTTGCCAGAGTGATGATCTTCTTGGACTGGATCCAATCAAAAATCAATGGT
	CCTGCTTCACTTCAGACAAATAATAAATGCAAAACCTTAAAACAACAATTGCCACCAC
	CCACACCTTCACCAGACAGTGCATCTTGGCCAGGTTGTTGCTCTGAAGCAGAGCTAGA
	AAAGCCTAGAGGCTTTTTTCCCACACCACGGTATCTACTCGATTATAGAGGAAGACTG
	GAATGTTCTTGGGTGCTCAGAGTTTCACCAAGCAGTATGGCAAAATTTACCATTGAGT
	ATCTGTCACTCCTGGGGTCTCCTGTGTGTCAAGACTCAGTTCTAATTATTTATGAAGA
AAGACACAGTAAGAGAAAGACGGCAGGTGGATTACATGGAAGAAGACTTTACTCAATG
	ACTTTCATGAGTCCTGGACCGCTGGTGAGGGTGACATTCCATGCCCTTGTACGAGGTG
	CATTTGGTATAAGCTATATTGTCTTGAAAGTCCTAGGTCCAAAGGACAGTAAAATAAC
	CAGACTTTCCCAAAGTTCAAACAGAGAGCACTTGCTCCCTTGTGAGGATGTTCTTCTG
	ACCAAGCCAGAAGGGATCATGCGGATCCCAAGAAATTCTCACAGAACTACTATGGGCT
	CATTTACATGGCTCCAAGAAAGAGTTTATCTTGATATCCAGTGCTGCTTACCTGACTG
	TGCATTTTAAGACTGATGAGTCTGAGAGAAAGAGGTTTTAAGCTTATTTTAGAAGAGA
	TGATTCAGGAGCAATCACAGAAGAGCAATATTGAGACCCAATTTCCTATCAGTGGAGA
	GTTTTCACTACTAATCTGGTGCCAGACTCCCACAACCTGACCCTGCT
	ORF Start: ATG at 8	ORF Stop: TAA at 2966
	SEQ ID NO:50	986 aa	MW at 109103.2 kD
NOV 12a,	MVNMKSKEPAVGSRFFSRISSWRNSTVTGHPWQVSLKSDEHHFCGGSLIQEDRVVTAA
CG92293-01	HCLDSLSEKQLKNITVTSGEYSLFQKDKQEQNIPVSKIITHPEYNSREYMSPDIALLY
Protein Sequence	LKHKVKFGNAVQPICLPDSDDKVEPGILCLSSGWGKISKTSEYSNVLQEMELPIMDDR
	ACNTVLKSMNLPPLGRTMLCAGFPDGGMDACQGDSGGPLVCRRGGGIWILAGITSWVA
	GCAGGSVPVRNNHVKASLGIFSKVSELMDFITQNLFTGSIYYIFFTFPYPSLYVWKIM
	VPEDKIILIKFTSLDMEKQVGCDHDYVSLRSSSGVLFSKVCGKILPSPLLAETSEAMV
	PFVSDTEDSGSGFELTVTAVQKSEAGSGCGSLAILVEEGTNHSAKYPDLYPSNTRCHW
	FICAPEKHIIKLTFEDFAVKFSPNCIYDAVVIYGDSEEKHKLAKLCGMLTITSIFSSS
	NMTVIYFKSDGKNRLQGFKARFTILPSESLNKFEPKLPPQNNPVSTVKAILHDVCGIP
	PFSPQWLSRRIAGGEEACPHCWPWQVGLRFLGDYQCGGAIINPVWILTAAHCVQLKNN
	PLSWTIIAGDHDRNLKESTEQVRRAKHIIVHEDFNTLSYDSDIALIQLSSPLEYNSVV
	RPVCLPHSAEPLFSSEICAVTGWGSISADGGLASRLQQIQVHVLEREVCEHTYYSAHP
	GGITEKMICAGFAASGEKDFCQGDSGGPLVCRHENGPFVLYGIVSWGAGCVQPWKPGV
	FARVMIFLDWIQSKINGPASLQTNNKCKTLKQQLPPPTPSPDSASWPGCCSEAELEKP
	RGFFPTPRYLLDYRGRLECSWVLRVSPSSMAKFTIEYLSLLGSPVCQDSVLIIYEERH
	SKRKTAGGLHGRRLYSMTFMSPGPLVRVTFHALVRGAFGISYIVLKVLGPKDSKITRL
	SQSSNRERLVPCEDVLLTKPEGIMRIPRNSHRTTMGSFTWLQERVYLDIQCCLPDCAF
	SEQ ID NO:51	2929 bp
NOV 12b,	AATTCGCATGGTCAACATGAAAAGTAAGGAACCTGCCGTGGGATCTAGATTCTTCTCT
CG92293-02 DNA	AGAATTAGTAGTTGGAGAAATTCAACAGTGACTGGACATCCATGGCAGGTCTCCCTAA
Sequence	AATCAGATGAGCACCACTTCTGTGGAGGAAGCTTGATTCAAGAAGATCGGGTTGTTAC
	AGCAGCACACTGCCTGGACAGCCTCAGTGAGAAGCAGCTGAAGAATATAACTGTGACT
	TCTGGGGAGTACAGCCTCTTTCAGAAGGATAAGCAAGAACAGAATATTCCTGTCTCAA
	AAATTATTACCCATCCTGAATACAACAGCCGTGAATATATGAGTCCTGATATTGCACT
	GCTGTATCTAAAACACAAAGTCAAGTTTGGAAATGCTGTTCAGCCAATCTGTCTTCCT
	GACAGCGATGATAAAGTTGAACCAGGAATTCTTTGCTTATCCAGTGGATGGGGCAAGA
	TTTCCAAAACATCAGAATATTCAAATGTCCTACAAGAAATGGAACTTCCCATCATGGA
	TGACAGAGCGTGTAATACTGTGCTCAAGAGCATGAACCTCCCTCCCCTGGGAAGGACC
	ATGCTGTGTGCTGGCTTCCCTGATGGGGGAATGGACGCCTGCCAGGGGGACTCTGGAG
	GACCACTGGTTTGTAGAAGAGGTGGTGGAATCTGGATTCTTGCTGGGATAACTTCCTG
	GGTAGCTGGTTGTGCTGGAGGTTCAGTTCCCGTAAGAAACAACCATGTGAAGGCATCA
	CTTGGCATTTTCTCCAAAGTGTCTGAGTTGATGGATTTTATCACTCAAAACCTGTTCA
	CAGGTTCCATTTATTACATTTTCTTCACCTTCCCCTACCCCAGCTTATATGTTTGGAA
	AATAATGGTACCAGAAGATAAAATAATCCTGATAAAATTTACAAGTTTAGACATGGAA
	AAGCAAGTTGGATGTGATCATGACTATGTATCTTTACGATCAAGCAGTGGAGTGCTTT
	TTAGTAAGGTCTGTGGAAAAATATTGCCTTCACCATTGCTGGCAGAGACCAGTGAGGC
	CATGGTTCCATTTGTTTCTGATACAGAAGACAGTGGCAGTGGCTTTGAGCTTACCGTT
	ACTGCTGTACAGAAGTCAGAAGCAGGGTCAGGTTGTGGGAGTCTCGCTATATTGGTAC
	AACAAGGGACAAATCACTCTGCCAAGTATCCTGATTTGTATCCCAGTAACACAAGGTG
	TCATTGGTTCATTTGTGCTCCAGAGAAGCACATTATAAAGTTGACATTTGAGGACTTT
	GCTGTCAAATTTAGTCCAAACTGTATTTATGATGCTGTTGTGATTTACGGTGATTCTG
	AAGAAAAGCACAAGTTAGCTAAACTTTGTGGAATGCTGACCATCACTTCAATATTCAG
	TTCTAGTAACATGACGGTGATATACTTTAAAAGTGATGGTAAAAATCGTTTACAAGGC
	TTCAAGGCCAGATTTACCATTTTGCCCTCAGAGTCTTTAAACAAATTTGAACCAAAGT
	TACCTCCCCAAAACAATCCTGTATCTACCGTAAAAGCTATTCTGCATGATGTCTGTGG
	CATCCCTCCATTTAGTCCCCAGTGGCTTTCCAGAAGAATCGCAGGAGGGGAAGAAGCC
	TGCCCCCACTGTTGGCCATOGCAGGTGGGTCTGAGGTTTCTAGGCGATTACCAATGTG
	GAGGTGCCATCATCAACCCAGTGTGGATTCTGACCGCAGCCCACTGTGTGCAATTGAA
	GAATAATCCACTCTCCTGGACTATTATTGCTGGGGACCATGACAGAAACCTGAAGGAA
	TCAACAGAGCAGGCAGATGGTGGCCTAGCAAGTCGCCTACAGCAGATTCAAGTGCATG
	TGTTAGAAAGAGAGGTCTGTGAACACACTTACTATTCTGCCCATCCAGGAGGGATCAC
	AGAGAAGATGATCTGTGCTGGCTTTGCAGCATCTGGAGAGAAAGATTTCTGCCAGGGA
	GACTCTGGTGGGCCACTAGTATGTAGACATGAAAATGGTCCCTTTGTCCTCTATGGCA
	TTGTCAGCTGGGGAGCTGGCTGTGTCCAGCCATGGAAGCCGGGTGTATTTGCCAGAGT
	GATGATCTTCTTGGACTGGATCCAATCAAAAATCAATGGTCCTGCTTCACTTCAGACA
	AATAATAAATGCAAAACCTTAAAACAACAATTGCCACCACCCACACCTTCACCAGACA
	GTGCATCTTGGCCAGGTTGTTGCTCTGAAGCAGAGCTAGAAAAGCCTAGAGGCTTTTT
	TCCCACACCACGGTATCTACTGGATTATAGAGGAAGACTGGAATGTTCTTGGGTGCTC
	AGAGTTTCACCAAGCAGTATGGCAAAATTTACCATTGAGTATCTGTCACTCCTGGGGT
	CTCCTGTGTGTCAAGACTCAGTTCTAATTATTTATGAAGAAAGACACAGTAAGAGAAA
	GACGGCAGGTGGATTACATGGAAGAAGACTTTACTCAATGACTTTCATGAGTCCTGGA
	CCGCTGGTGAGGGTGACATTCCATGCCCTTGTACGAGGTGCATTTGGTATAAGCTATA
	TTGTCTTGAAAGTCCTAGGTCCAAAGGACAGTAAAATAACCAGACTTTCCCAAAGTTC
	AAACAGAGAGCACTTGGTCCCTTGTGAGGATGTTCTTCTGACCAAGCCAGAAGGGATC
	ATGCGGATCCCAAGAAATTCTCACAGAACTACTATGGGCTCATTTACATGGCTCCAAG
	AAAGAGTTTATCTTGATATCCAGTGCTGCTTACCTGACTGTGCATTTTAAGACTGATG
	AGTCTGAGAGAAAGAGGTTTTAAGCTTATTTTAGAAGAGATGATTCAGGAGCAATCAC
	AGAAGAGCAATATTGAGACCCAATTTCCTATCAGTGGAGAGTTTTCACTACTAATCTG
	GTGCCAGACTCCCACAACCTGACCCTGCT
	ORF Start: ATG at 8	ORF Stop: TAA at 2774
	SEQ ID NO: 52	922aa	MW at 102051.3 kD
NOV12b,	MVNMKSKEPAVGSRFFSRISSWRNSTVTGHPWQVSLKSDEHHFCGGSLIQEDRVVTAA
CG92293-02	HCLDSLSEKQLKNITVTSGEYSLFQKDKQEQNIPVSKIITHPEYNSREYMSPDIALLY
Protein Sequence	LKHKVKFGNAVQPICLPDSDDKVEPGILCLSSGWGKISKTSEYSNVLQEMELPIMDDR
	ACNTVLKSMNLPPLGRTMLCAGFPDGGMDACQGDSGGPLVCRRGGGIWILAGITSWVA
	GCAGGSVPVRNNHVKASLGIFSKVSELMDFITQNLFTGSIYYIFFTFPYPSLYVWKIM
	VPEDKIILIKFTSLDMEKQVGCDHDYVSLRSSSGVLFSKVCGKILPSPLLAETSEAMV
	PFVSDTEDSGSGFELTVTAVQKSEAGSGCGSLAILVEEGTNHSAKYPDLYPSNTRCHW
	FICAPEKHIIKLTFEDFAVKFSPNCIYDAVVIYGDSEEKHKLAKLCGMLTITSIFSSS
	NMTVIYFKSDGKNRLQGFKARFTILPSESLNKFEPKLPPQNNPVSTVKAILHDVCGIP
	PFSPQWLSRRIAGGEEACPHCWPWQVGLRFLGDYQCGGAIINPVWILTAAHCVQLKNN
	PLSWTIIAGDHDRNLKESTEQADGGLASRLQQIQVHVLEREVCEHTYYSAHPGGITEK
	MICAGFAASGEKDFCQGDSGGPLVCRHENGPFVLYGIVSWGAGCVQPWKPGVFARVMI
	FLDWIQSKINGPASLQTNNKCKTLKQQLPPPTPSPDSASWPGCCSEAELEKPRGFFPT
	PRYLLDYRGRLECSWVLRVSPSSMAKFTIEYLSLLGSPVCQDSVLIIYEERHSKRKTA
	GGLHGRRLYSMTFMSPGPLVRVTFHALVRGAFGISYIVLKVLGPKDSKITRLSQSSNR
	EHLVPCEDVLLTKPEGIMRIPRNSHRTTMGSFTWLQERVYLDIQCCLPDCAF

[0331] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 12B.

TABLE 12B
Comparison of NOV12a against NOV12b.
	Protein	NOV12a Residues/	Identities/Similarities
	Sequence	Match Residues	for the Matched Region
	NOV12b	1 . . . 986	894/988 (90%)
		1 . . . 922	903/988 (90%)

[0332] Further analysis of the NOV12a protein yielded the following properties shown in Table 12C.

TABLE 12C
Protein Sequence Properties NOV12a
PSort     0.4820 probability located in mitochondrial matrix space; 0.4298 probability
analysis: located in microbody (peroxisome); 0.1907 probability located in mitochondrial
          inner membrane; 0.1907 probability located in mitochondrial intermembrane
          space
SignalP   No Known Signal Sequence
analysis:

[0333] 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 12D.

TABLE 12D
Geneseq Results for NOV12a
			Identities/
			Similarities
		NOV12a	for the
Geneseq	Protein/Organism/Length	Residues/	Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
ABG24246	Novel human diagnostic protein	1 . . . 771	660/771 (85%)	0.0
	#24237 - Homo sapiens, 913 aa.	13 . . . 738	670/771 (86%)
	[WO200175067-A2, 11-OCT-2001]
ABG24246	Novel human diagnostic protein	1 . . . 771	660/771 (85%)	0.0
	#24237 - Homo sapiens, 913 aa.	13 . . . 738	670/771 (86%)
	[WO200175067-A2, 11-OCT-2001]
ABG19887	Novel human diagnostic protein	1 . . . 770	659/770 (85%)	0.0
	#19878 - Homo sapiens, 1576 aa.	852 . . . 1576	669/770 (86%)
	[WO200175067-A2, 11-OCT-2001]
ABG14588	Novel human diagnostic protein	1 . . . 770	659/770 (85%)	0.0
	#14579 - Homo sapiens,	852 . . . 1576	669/770 (86%)
	1576 aa. [WO200175067-A2,
	11-OCT-2001]
ABG10218	Novel human diagnostic protein	1 . . . 770	659/770 (85%)	0.0
	#10209 - Homo sapiens,	852 . . . 1576	669/770 (86%)
	1576 aa. [WO200175067-A2,
	11-OCT-2001]

[0334] 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 12E.

TABLE 12E
Public BLASTP Results for NOV12a
		NOV12a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q91674	POLYPROTEIN - Xenopus laevis	15 . . . 955	413/969 (42%)	0.0
	(African clawed frog), 1524 aa.	53 . . . 995	567/969 (57%)
P79953	OVIDUCTIN - Xenopus laevis	15 . . . 778	291/798 (36%)	e−146
	(African clawed frog), 1004 aa.	42 . . . 828	430/798 (53%)
Q90WD8	OVIDUCTIN - Bufo japonicus	10 . . . 801	284/829 (34%)	e−141
	(Japanese toad), 974 aa.	41 . . . 849	436/829 (52%)
Q9BK47	SEA STAR REGENERATION-	513 . . . 769	111/264 (42%)	2e−51
	ASSOCIATED PROTEASE SRAP	12 . . . 264	156/264 (59%)
	- Luidia foliolata, 267 aa.
O96899	PLASMINOGEN ACTIVATOR	532 . . . 767	104/241 (43%)	8e−49
	SPA - Scolopendra subspinipes, 277	33 . . . 264	148/241 (61%)
	aa.

[0335] PFam analysis indicates that the NOVI2a protein contains the domains shown in Table 12F.

TABLE 12F
Domain Analysis of NOV12a
		Identities/
		Similarities
Pfam	NOV12a	for the	Expect
Domain	Match Region	Matched Region	Value
trypsin: domain 1 of 2	19 . . . 263	100/275 (36%)	2.5e−76
		186/275 (68%)
CUB: domain 1 of 3	266 . . . 365	31/116 (27%)	7.5e−06
		64/116 (55%)
CUB: domain 2 of 3	377 . . . 486	40/116 (34%)	1.8e−22
		73/116 (63%)
trypsin: domain 2 of 2	533 . . . 765	109/264 (41%)	2.5e−82
		182/264 (69%)
CUB: domain 3 of 3	804 . . . 912	23/118 (19%)	7.3e−05
		70/118 (59%)

Example 13

[0336] 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:53	2544 bp
NOV13a,	TCCTGGGCCCCAGCCCCGCGCAGGCCAAGGATGAGGCCGAGGCCCGAAGGTAGGGGGC
CG92384-01 DNA	TCCGGGCGGGAGTCGCGCTGTCCCCCGCGCTACTGCTGCTGCTGCTGCTGCCGCCGCC
Sequence	GCCGACGCTGCTGGGGCGCCTGTGGGCAGCGGGCACACCCTCGCCGTCGGCGCCCGGA
	GCTCGGCAGGACGGCGCGCTGGGAGCCGGCCGCGTCAAACGCGGCTGGGTGTGGAACC
	AGTTCTTCGTGGTAGAGGAGTACACGGGCACGGAGCCCCTGTATGTGGGCAAGATCCA
	CTCCGACTCAGACGAGGGTGACGGGGCCATCAAGTACACCATCTCAGGCGAGGGTGCT
	GGGACCATCTTCCTGATCGACGAGCTGACAGGCGACATTCATGCCATGGAGCGCCTGG
	ACCGCGAGCAGAAAACCTTCTACACGCTGCGGGCCCAGGCTCGGGATCGCGCCACCAA
	CCGCCTACTGGAGCCCGAGTCGGAGTTCATCATCAAGGTGCAGCACATCAATGACAGT
	GAGCCCCGCTTCCTGCACGGCCCCTATATTGCCAGCGTGGCCGAGCTCTCACCTACAG
	GTACGTCGGTGATGCAGGTGATGGCCTCGGATGCGGATGACCCCACGTACGGCAGCAG
	CGCTCGGCTGGTGTACAGCGTGCTGGACGGCGAGCACCACTTCACCGTGGACCCCAAG
	ACCGGTGTAATCCGGACGGCTGTGCCTGACCTTGACCGCGAGAGCCAGGAGCGCTACG
	AGGTGGTGATCCAGGCCACAGACATGGCGGGTCAGCTGGGTGGCCTCTCGGGCTCCAC
	TACCGTCACCATCGTAGTCACCGACGTCAATGACAACCCGCCCCGTTTCCCGCAGGAG
	ATGTACCAGTTCAGCATCCAGGAGTCAGCCCCCATTGGAACGGCTGTGGGACGTGTGA
	AGGCTGAGGACTCAGACGTGGGAGAGAACACAGACATGACTTACCACCTTAAGGACGA
	GAGCAGCAGCGGCGGCGATGTGTTCAAGGTCACCACAGACAGCGACACTCAGGAGGCC
	ATCATCGTAGTGCAGAAGCGCCTGGACTTCGAATCCCAGCCCGTGCACACCGTGATCC
	TGGAGGCCCTCAACAAGTTCGTGGACCCCCGCTTCGCCGACCTGGGCACGTTCCGCGA
	CCAGGCGATCGTGCGCGTGGCCGTGACCGACGTGGACGAGCCCCCCGAGTTCCGGCCG
	CCCTCCGGCCTCCTGGAGGTGCAGGAGGACGCGCAGGTGGGCTCCCTGGTCGGCGTGG
	TGACGGCGCGGGACCCCGACGCCGCCAACCGGCCCGTCCGGTACGCCATTGACCGCGA
	ATCAGATTTGGACCAGATCTTCGATATCGATGCGGACACAGGCGCCATCGTGACTGGC
	AAGGGGCTGGACCGCGAGACGGCCGGCTGGCACAACATCACACTGCTGGCCATGGAGG
	CGGACAATCATGCACAGCTATCCCGGGCATCCCTAAGGATCCGAATCCTGGATGTGAA
	CGACAATCCCCCAGAACTGGCCACACCCTACGAGGCAGCTGTATGCGAGGATGCCAAG
	CCAGGCCAGCTCATCCAGACCATCAGCGTGGTGGACAGAGACGAGCCCCAAGGCGGGC
	ACCGCTTCTATTTCCGCCTGGTGCCTGAAGCTCCCAGCAACCCTCATTTCTCTCTGCT
	TGACATCCAAGACAACACCGCTGCAGTGCACACGCAGCACGTGGGCTTCAACCGGCAG
	GAGCAGGACGTGTTCTTCCTGCCCATCCTGGTGGTAGACAGTGGGCCGCCCACACTGA
	GCAGCACAGGCACGCTCACCATCCGCATCTGTGGCTGCGACAGCTCCGGCACCATCCA
	GTCCTGCAACACCACGGCCTTTGTCATGGCCGCCTCCCTCAGCCCCGGCGCCCTCTTG
	GTCTGCGTTCTCATCCTGGTTGTCCTGGTGCTGCTGATCCTCACCCTCAGGCGCCACC
	ACAAGAGCCACCTGAGCTCGGACGAGGATGAAGACATGCGGGACAACGTCATCATATA
	CAACGACGAAGGCGGCGGCGAGCAGGACACCGAAGCCTACGACATGTCGGCGCTGCGG
	AGCCTCTACGACTTCGGCGAGCTCAAGGGCGGCGACGCGCGCGGCAGCGCGGGCAGCC
	CCCCGCAGGCCCACCTGCCCTCCGAGCGCCACTCGCTCCCGCAGCGGCCCCCGAGCCC
	CGAGCCAGACTTCTCAGTGTTCAGGGACTTCATCAGCCGCAAGGTGGCACTGGCGGAC
	GGGGACCTGTCGGTGCCGCCCTACGACGCCTTCCAGACCTACGCCCTCGAGCGCGCGG
	ACTCGCCCGCCGCCTCGCTCAGCTCCCTGCACAGCGGCTCGTCCGCCTCCGAGCAGGA
	CTTCGCCTATTTCAGCATGTGGGGTCATTCGGGCTCCGAGCAGGACTTCGCCTATCTC
	AGCAGCTGGGGTCCGCGCTTCCGGCCCCTGGCCGCGCTCTACGCCGGCCACCGCGGGG
	ACGACGAGGCCCAGGCCTCCTAGCCCCTCGCCCTGCCGTCGGGGCGCGGC
	ORF Start: ATG at 31	ORF Stop: TAG at 2515
	SEQ ID NO: 54	828 aa	MW at 89732.6 kD
NOV13a,	MRPRPEGRGLRAGVALSPALLLLLLLPPPPTLLGRLWAAGTPSPSAPGARQDGALGAG
CG92384-01	RVKRGWVWNQFFVVEEYTGTEPLYVGKIHSDSDEGDGAIKYTISGEGAGTIFLIDELT
Protein Sequence	GDIHANERLDREQKTFYTLRAQARDRATNRLLEPESEFIIKVQDINDSEPRFLHGPYI
	GSVAELSPTGTSVMQVMASDADDPTYGSSARLVYSVLDGEHHFTVDPKTGVIRTAVPD
	LDRESQERYEVVIQATDMAGQLGGLSGSTTVTIVVTDVNDNPPRFPQEMYQFSIQESA
	PIGTAVGRVKAEDSDVGENTDMTYHLKDESSSGGDVFKVTTDSDTQEAIIVVQKRLDF
	ESQPVHTVILEALNKFVDPRFADLGTFRDQAIVRVAVTDVDEPPEFRPPSGLLEVQED
	AQVGSLVGVVTARDPDAANRPVRYAIDRESDLDQIFDIDADTGAIVTGKGLDRETAGW
	HNITVLAMEADNHAQLSRASLRIRILDVNDNPPELATPYEAAVCEDAKPGQLIQTISV
	VDRDEPQGGHRFYFRLVPEAPSNPHFSLLDIQDNTAAVHTQHVGFNRQEQDVFFLPIL
	VVDSGPPTLSSTGTLTIRICGCDSSGTIQSCNTTAFVMAASLSPGALLVCVLILVVLV
	LLILTLRRHHKSHLSSDEDEDMRDNVIIYNDEGGGEQDTEAYDMSALRSLYDFGELKG
	GDGGGSAGSPPQAHLPSERHSLPQGPPSPEPDFSVFRDFISRKVALADGDLSVPPYDA
	FQTYALEGADSPAASLSSLHSGSSGSEQDFAYFSMWGHSGSEQDFAYLSSWGPRFRPL
	AALYAGHRGDDEAQAS

[0337] Further analysis of the NOV13a protein yielded the following properties shown in Table 13B.

TABLE 13B
Protein Sequence Properties NOV13a
PSort     0.4600 probability located in plasma membrane; 0.1561
analysis: probability located in microbody (peroxisome); 0.1000
          probability located in endoplasmic reticulum
          (membrane); 0.1000 probability located in endoplasmic
          reticulum (lumen)
SignalP   Cleavage site between residues 34 and 35
analysis:

[0338] 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/	Match	the Matched	Expect
Identifier	Length [U.S Pat. No. #, Date]	Residues	Region	Value
AAU09864	Novel human secreted protein #5 -	41 . . . 821	412/784 (52%)	0.0
	Homo sapiens, 801 aa.	38 . . . 796	540/784 (68%)
	[WO200179454-A1, 25-OCT-2001]
AAM78375	Human protein SEQ ID NO 1037 -	50 . . . 825	393/779 (50%)	0.0
	Homo sapiens, 788 aa.	43 . . . 788	546/779 (69%)
	[WO200157190-A2, 09-AUG-2001]
AAW13132	Full length human cadherin-8 -	17 . . . 824	394/816 (48%)	0.0
	Homo sapiens, 793 aa.	7 . . . 792	560/816 (68%)
	[U.S. Pat. No. 5597725-A, 28-JAN-1997]
AAW25635	Human cadherin-8 - Homo sapiens,	17 . . . 824	394/816 (48%)	0.0
	793 aa. [U.S. Pat. No. 5646250-A, 08-JUL-1997]	7 . . . 792	560/816 (68%)
AAW13126	Full length rat cadherin-8 - Rattus	17 . . . 824	390/813 (47%)	0.0
	rattus, 799 aa. [U.S. Pat. No. 5597725-A, 28-	14 . . . 798	557/813 (67%)
	JAN-1997]

[0339] 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
Q9UJ99	DJ998H6.1 (ORTHOLOG OF RAT	1 . . . 828	810/843 (96%)	0.0
	PB-CADHERIN) - Homo sapiens	1 . . . 828	811/843 (96%)
	(Human), 828 aa.
Q9WTP5	PB-CADHERIN - Mus musculus	1 . . . 828	762/833 (91%)	0.0
	(Mouse), 813 aa.	1 . . . 813	777/833 (92%)
Q63315	LONG TYPE PB-CADHERIN -	1 . . . 828	761/833 (91%)	0.0
	Rattus norvegicus (Rat), 813 aa.	1 . . . 813	775/833 (92%)
Q63561	SHORT TYPE PB-CADHERIN -	1 . . . 688	637/695 (91%)	0.0
	Rattus norvegicus (Rat), 694 aa.	1 . . . 690	649/695 (92%)
Q9ULB5	Cadherin-7 precursor - Homo	56 . . . 816	420/764 (54%)	0.0
	sapiens (Human), 785 aa.	41 . . . 776	552/764 (71%)

[0340] PFam analysis indicates that the NOV13a protein contains the domains shown in Table 13E.

TABLE 13E
Domain Analysis of NOV13a
		Identities/
		Similarities
	NOV13a Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
cadherin: domain 1 of 5	68 . . . 159	32/107 (30%)	2.4e−12
		60/107 (56%)
FBPase: domain 1 of 1	200 . . . 225	12/28 (43%)	2.9
		20/28 (71%)
cadherin: domain 2 of 5	173 . . . 168	46/109 (42%)	1.3e−29
		80/109 (73%)
cadherin: domain 3 of 5	282 . . . 386	30/111 (27%)	6.5e−14
		75/111 (68%)
cadherin: domain 4 of 5	399 . . . 490	37/108 (34%)	1.2e−17
		69/108 (64%)
cadherin: domain 5 of 5	503 . . . 600	27/113 (24%)	1.3e−10
		71/113 (63%)
Cadherin_C_term:	646 . . . 819	75/179 (42%)	1.3e−65
domain 1 of 1		147/179 (82%)

Example 14

[0341] 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:55	1170 bp
NOV14a,	TAAGCTTCTCTGAACATGCAGAGCAGTGGTAACTATGAGGAGGCACAGTCTCTCCTGA
CG92455-01 DNA	GCATGACTCTGGCTGTTGGTGTGGCTTTGCTGCAGCTGCCGTGTGCCATTGATGATCC
Sequence	TGCTCCTCTTCCTTCGGGAAAGCTGCCTGATGGAGTCTGGCTCCTGGAGCTGAGCCAC
	AATAATCTCAGCCATCTGCCGGCTGGCGCCTTCCAGGGCTTTTGGGGACTGCGGGTGT
	TGCTGCTTTCTCTCAATATCCTGCGGGATCTGTCTGATGGGGCCCTAGGGGGCCTCAG
	TTTCCTGGAGCAGCTGAACCTCAGCCATAACCAGCTGGCCCATCTGCCCACAGACTTC
	TCGGCTACCCTGGGCTCTCTGCTCTGCCTGGACCTCTCTCACAACCTACTCACTTCCC
	TGGACCCCACCAGCCTGTGGCGCCTGGGGGGCCTGGAGCAGCTCAACCTGAGCCACAA
	CCAGCTGGCTGAACTGGCCGCAGGGGTCTTTGGGGGCCTCTTCCACCTACACTGGCTC
	TCGCTGGCTGGGAACCAGCTGCAGCGGGTGAAGGGTGCTGCCCTGACCACTGTGCCCG
	GCTTGGAAGTCCTCTCTGTAGCTGGGAATGACATCAGTGCCTTCGGAAAGTTGGGTCA
	CCTGCGGCACTTGAGTGTCGTAGACCTGGGCATCCTGACTTGCGCTGGGCCCGAAAGG
	CTGTCAGGGGCAGTGCTGAGTGGTGTGGAGGCCCAGCTTTGCCTGGCTGAGACTGCCA
	CTGTGCTGGGCATCACAGGCACCGTGCTGCTCACAGTGGCTGTGGCTGTGCTGATGGC
	TGAGCGCAAGCGAAGACAGGGCCCGCAAGAAGCCGGGGAGCTGGGGAGCTTTCTGGAG
	AGGCTATTTAATCAGCAGGCAGATCAACAGGCCAAAATTTCCACCATAACTGCAAACT
	TGAATGCGGATGAATGGATTACAACATGGTCAAACCTTGCAATGAGAGGCATTATAAT
	GTATGGTGCTATAATTGATAGTGATTACCGGGGAGAGTTAAAGGTCATTTTATACAAT
	ACCACTCCAGATTCTTTTGCTATAAAACCGCACATGCAGGTTGCTCAATTGTTAGTGG
	TATCTTGTCAACAACCCCCGAGGAAATTTCCACCCCAATAGAAACAACATAAACG
	GAACATTCAG
	ORF Start: ATG at 16	ORF Stop: TAG at 1141
	SEQ ID NO: 56	375 aa	MW at 40138.8 kD
NOV14a,	MQSSGNYEEAQSLLSMTLAVGVALLQLPCAIDDPAPLPSGKLPDGVWLLELSHNNLSH
CG92455-01	LPAGAFQGFWGLRVLLLSLNILRDLSDGALGGLSFLEQLNLSHNQLAHLPTDFSATLG
Protein Sequence	SLLCLDLSHNLLTSLDPTSLWRLGGLEQLNLSHNQLAELAAGVFGGLFHLHWLSLAGN
	QLQRVKGAALTTVPGLEVLSVAGNDISAFGKLGHLRHLSVVDLGILTCAGPERLSCAV
	LSGVEAQLCLAETATVLGITGTVLLTVAVAVLMAERKRRQGPQEAGELGSFLERLFNQ
	QADQQAKISTITANLNADEWITTWSNLANRGIIMYGAIIDSDYRGELKVILYNTTPDS
	FAIKPQMQVAQLLVVSCQQPPRKFPPQ

[0342] Further analysis of the NOV14a protein yielded the following properties shown in Table 14B.

TABLE 14B
Protein Sequence Properties NOV14a
PSort     0.4600 probability located in plasma membrane; 0.1285
analysis: probability located in microbody (peroxisome); 0.1000
          probability located in endoplasmic reticulum
          (membrane); 0.1000 probability located in endoplasmic
          reticulum (lumen)
SignalP   Cleavage site between residues 31 and 32
analysis:

[0343] 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/	Match	the Matched	Expect
Identifier	Length [Patent #, Date]	Residues	Region	Value
ABG16717	Novel human diagnostic protein	287 . . . 375	73/89 (82%)	5e−33
	#16708 - Homo sapiens, 550 aa.	182 . . . 268	78/89 (87%)
	[WO200l75067-A2, 11-OCT-2001]
ABG16717	Novel human diagnostic protein	287 . . . 375	73/89 (82%)	5e−33
	#16708 - Homo sapiens, 550 aa.	182 . . . 268	78/89 (87%)
	[WO200175067-A2, 11-OCT-2001]
ABG05979	Novel human diagnostic protein	272 . . . 367	69/98 (70%)	2e−30
	#5970 - Homo sapiens, 258 aa.	55 . . . 152	78/98 (79%)
	[WO200175067-A2, 11-OCT-2001]
ABG05979	Novel human diagnostic protein	272 . . . 367	69/98 (70%)	2e−30
	#5970 - Homo sapiens, 258 aa.	55 . . . 152	78/98 (79%)
	[WO200175067-A2, 11-OCT-2001]
AAB82352	Protein sequence SEQ ID NO. 2 -	42 . . . 250	79/213 (37%)	8e−20
	Homo sapiens, 794 aa.	93 . . . 303	103/213 (48%)
	[WO200138357-A2, 31-MAY-2001]

[0344] 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	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9N4G6	Y71F9B.8 PROTEIN (1D304) -	45 . . . 271	80/248 (32%)	6e−20
	Caenorhabditis elegans, 542 aa.	190 . . . 436	127/248 (50%)
CAC42683	SEQUENCE 1 FROM PATENT	42 . . . 250	79/213 (37%)	2e−19
	WO0142286 - Homo sapiens	93 . . . 303	103/213 (48%)
	(Human), 794 aa.
Q9UGS3	DJ756G23.1 (NOVEL LEUCINE	42 . . . 250	79/213 (37%)	2e−19
	RICH PROTEIN) - Homo sapiens	101 . . . 311	103/213 (48%)
	(Human), 797 aa (fragment).
O70211	INSULIN-LIKE GROWTH	44 . . . 236	74/215 (34%)	1e−18
	FACTOR BINDING PROTEIN	386 . . . 595	99/215 (45%)
	COMPLEX ACID-LABILE
	SUBUNIT - Rattus norvegicus (Rat),
	603 aa.
P70193	MEMBRANE GLYCOPROTEIN -	44 . . . 214	67/179 (37%)	3e−18
	Mus musculus (Mouse), 1091 aa.	237 . . . 415	92/179 (50%)

[0345] PFam analysis indicates that the NOV14a protein contains the domains shown in Table 14E.

TABLE 14E
Domain Analysis of NOV14a
		Identities/
		Similarities
	NOV14a	for the	Expect
Pfam Domain	Match Region	Matched Region	Value
LRR: domain 1 of 7	45 . . . 68	10/25 (40%)	1
		17/25 (68%)
LRR: domain 2 of 7	69 . . . 92	9/25 (36%)	4.2
		20/25 (80%)
LRR: domain 3 of 7	93 . . . 115	10/25 (40%)	0.39
		16/25 (64%)
LRR: domain 4 of 7	117 . . . 140	12/25 (48%)	0.057
		16/25 (64%)
LRR: domain 5 of 7	141 . . . 164	11/25 (44%)	0.0059
		19/25 (76%)
LRR: domain 6 of 7	165 . . . 188	6/25 (24%)	39
		15/25 (60%)
LRR: domain 7 of 7	189 . . . 210	7/25 (28%)	44
		16/25 (64%)
dUTPase: domain 1 of 1	269 . . . 375	28/139 (20%)	0.00014
		75/139 (54%)

Example 15

[0346] 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:57	2328 bp
NOV15a,	ATGCCCGGCTACAGTGCTCTTTCTAATAAACCCATGCTGGAAACAACCCAAATGTCTA
CG92531-01 DNA	TCACTAGAGGAATGGGTAAGCTACTTGTGGTACGGTGTGGTACCGAGAAGGCTGGACC
Sequence	AGCAGTTCCAGGCGGCATGGAGGGGCCCCGGAGCTCCACCCATGTCCCCTTCGTGCTG
	CCGCTTCTTGTACTTCTGCTCCTGCCCCCGGCTAGGCAGGCCGCCGCCCAGCGCTGCC
	CACAGGCCTGCATCTGTGACAACTCCAGGCGACACGTTGCCTGCCGGTACCAGAACCT
	CACTGAGGTGCCAGACGCCATCCCTGAGCTGACCCAGCGGCTGGACCTGCAGGGCAAT
	TTGCTGAAGGTGATCCCCGCAGCCGCCTTCCAGGGCGTGCCTCACCTCACACACCTGG
	ACCTGCGCCACTGCGAGGTGGAGCTGGTGGCCGAGGGCGCCTTCCGTGGCCTGGGCCG
	CCTGCTCCTGCTCAACCTGGCCTCCAACCACCTGCGTGAGCTGCCCCAGGAGGCGCTG
	GACCGGCTGGGCTCGTTGCGGCGGCTGGAGCTGGAGGGGAACGCACTGGAGGAGCTGC
	GGCCGGGGACGTTCGGGGCACTGGGTGCGCTGGCCACGCTAAACCTGGCCCACAACGC
	CCTGGTTTACCTGCCCGCCATGGCCTTCCAGGGGCTACTGCGCGTCCGCTGGCTGCGG
	CTGTCGCACAACGCGCTCAGCGTGCTGGCCCCCGAGGCCCTGGCTGGCCTGCCCGCCC
	TGAGACGGCTCAGCCTACACCACAACGAGCTCCAGGCTCTGCCCGGGCCTGTCTTGTC
	CCAGGCCCCCGGCCTGGCCCGTCTGGAGCTGGGCCACAACCCGCTCACCTACGCGGGC
	GAGGAGGACGGGCTGGCGCTGCCCGGCCTGCGGGAGCTGCTGCTGGACGGCGGGGCCC
	TGCAGGCCCTGGGTCCCAGGGCCTTCGCACACTGTCCGCGCCTGCACACCCTCGACCT
	CCGCGGGAACCAGCTAGACACCCTGCCCCCGCTGCAGGGCCCGGGCCAGCTGCGCCGG
	CTGCGGCTGCAGGGGAATCCGCTGTGGTGCGGCTGCCAGGCGCGGCCCCTACTCGAGT
	GGCTGGCGCGGGCGCGCGTGCGCTCGGACGGCGCGTGCCAGGGGCCGCGGCGCCTGCG
	GGGCGAGGCTCTGGACGCCCTGCGGCCCTGGGACCTGCGCTGCCCTGGGGACGCGGCG
	CAGGAAGAGGAAGAGCTGGAAGAGCGGGCTGTGGCCGGGCCCCGCGCCCCTCCGCGCG
	GCCCTCCGCGCGGCCCCGGGGAGGAGCGGGCAGTCGCGCCTTGCCCTCGCGCCTGCGT
	GTGCGTCCCCGACTCCCGGCACAGCAGCTGCGAGCGCTGCGGCCTGCAGGCCGTGCCC
	CGCGGCTTCCCCAGCGACACCCAGCTCCTGGACCTGAGGCGGAACCACTTCCCCTCGG
	TGCCCCGAGCGCCCTTCCCCGGCCTGGGCCACCTGGTGTCGCTGCACCTGCAGCACTG
	CGGCATCGCGGAGCTGGAAGCGGGCGCCCTGGCCGGGCTGGGCCGCCTGATCTACCTG
	TACCTCTCCGACAACCAGCTCGCAGGCCTCAGCGCTGCTGCCCTTGAAGGGGCTCCCC
	GCCTCGGCTACCTGTACCTAGAACGCAACCGTTTCCTGCAGGTGCCAGGGGCTGCCCT
	GCGCGCCCTGCCCAGCCTCTTCTCCCTGCACCTGCAGGACAACGCTGTGGACCGCCTG
	GCACCTGGGGACCTGGGGAGAACACGGGCCTTGCGCTGGGTCTACCTGAGTGGAAACC
	GCATCACCGAAGTGTCCCTTGGGGCGCTGGGCCCAGCTCGGGAGCTGGAGAAGCTGCA
	CCTGGACAGGAATCAGCTGCGAGAGGTGCCCACTGGGGCCTTGGAGGGGCTGCCTGCC
	CTCCTGGAGCTGCAGCTCTCGGGCAACCCACTCAGGGCCTTGCGTGACGGAGCCTTCC
	AGCCTGTGGGCAGGTCGCTGCAGCACCTCTTCCTGAACAGCAGTGCCCTGGAGCAGGT
	GGGCACTGGGCATCTGGCGGGGTTGGTGCAGGAGGCGGCACAAGGCCACAGGCAGCGT
	GCATTCACTCAACAAGCATTTGCCAGCCCCTTGGTGCCAGGCCTGGGGCCCGGGCTCC
	AGAGCCTGCACCTGCAGAAGAACCAGCTTCGGGCCCTGCCTGCCCTGCCCAGTCTCAG
	CCAGCTGGAGCTCATCGACCTCAGCAGCAATCCCTTCCACTGTGACTGCCAGCTGCTT
	CCGCTGCACAGGCACACCATGTCCATGCCCATCCGAGCAGCTTGTGGGGAGGGGCGGG
	TCCTGTGA
	ORF Start: ATG at 1	ORF Stop: TGA at 2326
	SEQ ID NO: 58	775 aa	MW at 83600.4 kD
NOV15a,	MPGYSALSNKPMLETTQMSITRGMGKLLVVRCGTEKAGPAVPGGMEGPRSSTHVPLVL
CG92531-01	PLLVLLLLAPARQAAAQRCPQACICDNSRRHVACRYQNLTEVPDAIPELTQRLDLQGN
Protein Sequence	LLKVIPAAAFQGVPHLTHLDLRHCEVELVAEGAFRGLGRLLLLNLASNHLRELPQEAL
	DGLGSLRRLELEGNALEELRPGTFGALGALATLNLAHNALVYLPANAFQGLLRVRWLR
	LSHNALSVLAPEALAGLPALRRLSLHHNELQALPGPVLSQARGLARLELGHNPLTYAG
	EEDGLALPGLRELLLDGGALQALGPRAFAHCPRLHTLDLRGNQLDTLPPLQGPGQLRR
	LRLQGNPLWCGCQARPLLEWLARARVRSDGACQGPRRLRGEALDALRPWDLRCPGDAA
	QEEEELEERAVAGPRAPPRGPPRGPGEERAVAPCPRACVCVPESRHSSCEGCGLQAVP
	RGFPSDTQLLDLRRNHFPSVPRAAFPGLGHLVSLHLQHCGIAELEAGALAGLGRLIYL
	YLSDNQLAGLSAAALEGAPRLGYLYLERNRFLQVPGAALRALPSLFSLHLQDNAVDRL
	APGDLGRTRALRWVYLSGNRITEVSLGALGPARELEKLHLDRNQLREVPTGALEGLPA
	LLELQLSGNPLRALRDGAFQPVGRSLQHLFLNSSGLEQVGTGHLAGLVQEAAQGHRQR
	AFTQQAFASPLVPGLGPCLQSLHLQKNQLRALPALPSLSQLELIDLSSNPFHCDCQLL
	PLHRHTMSMPIRAACGEGRVL

[0347] Further analysis of the NOV15a protein yielded the following properties shown in Table 15B.

TABLE 15B
Protein Sequence Properties NOV15a
PSort     0.7900 probability located in plasma membrane; 0.3000 probability located in
analysis: microbody (peroxisome); 0.3000 probability located in Golgi body; 0.2000
          probability located in endoplasmic reticulum (membrane)
SignalP   Cleavage site between residues 70 and 71
analysis:

[0348] 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 [Patent #,	Match	the Matched	Expect
Identifier	Data]	Residues	Region	Value
AAB82352	Protein sequence SEQ ID NO. 2 -	12 . . . 766	696/756 (92%)	0.0
	Homo sapiens, 794 aa.	1 . . . 728	703/756 (92%)
	[WO200138357-A2, 31-MAY-2001]
AAE03600	Human leucine-rich repeat-containing	12 . . . 766	696/756 (92%)	0.0
	protein, AZAD - Homo sapiens,	1 . . . 728	703/756 (92%)
	794 aa. [WO200142286-A2,
	14-JUN-2001]
AAB99488	Human chondroadherin protein	436 . . . 758	124/323 (38%)	2e−56
	sequence - Homo sapiens, 381 aa.	41 . . . 335	178/323 (54%)
	[WO200137861-A1, 31-MAY-2001]
AAR85888	WD-40 domain-contg. insulin-like	71 . . . 541	166/556 (29%)	8e−37
	growth factor binding protein -	35 . . . 537	209/556 (36%)
	Synthetic, 605 aa. [WO9521252-A2,
	10-AUG-1995]
AAB38400	Fragment of human secreted protein	39 . . . 450	137/441 (31%)	3e−31
	encoded by gene 3 clone HSYAV50 -	36 . . . 464	180/441 (40%)
	Homo sapiens, 723 aa.
	[WO200061623-A1, 19-OCT-2000]

[0349] 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	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9UGS3	DJ756G23.1 (NOVEL LEUCINE	43 . . . 766	684/724 (94%)	0.0
	RICH PROTEIN) - Homo sapiens	40 . . . 737	689/724 (94%)
	(Human), 797 aa (fragment).
CAC42683	SEQUENCE 1 FROM PATENT	12 . . . 766	696/756 (92%)	0.0
	WO0142286 - Homo sapiens	1 . . . 728	703/756 (92%)
	(Human), 794 aa.
O70210	CHONDROADHERIN	436 . . . 758	125/323 (38%)	3e-56
	PRECURSOR - Rattus norvegicus	18 . . . 312	178/323 (54%)
	(Rat), 358 aa.
Q96RJ5	CHONDROADHERIN - Homo	436 . . . 758	124/323 (38%)	6e-56
	sapiens (Human), 359 aa.	19 . . . 313	178/323 (54%)
A53860	chondroadherin precursor - bovine,	436 . . . 758	124/323 (38%)	1e-55
	361 aa.	21 . . . 315	178/323 (54%)

[0350] PFam analysis indicates that the NOV15a protein contains the domains shown in Table 15E.

TABLE 15E
Domain Analysis of NOV15a
		Identities/
	NOV15a	Similarities
	Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
Trypan_glycop:	56 . . . 76	10/21 (48%)	2.7
domain 1 of 1		20/21 (95%)
GASA: domain 1 of 1	51 . . . 100	16/109 (15%)	9.8
		33/109 (30%)
LRRNT: domain 1 of 2	76 . . . 105	12/31 (39%)	1.9e−05
		21/31 (68%)
LRR: domain 1 of 19	107 . . . 130	8/25 (32%)	1.8
		18/25 (72%)
LRR: domain 2 of 19	131 . . . 154	6/25 (24%)	2.8
		19/25 (76%)
LRR: domain 3 of 19	155 . . . 178	9/25 (36%)	0.087
		19/25 (76%)
LRR: domain 4 of 19	179 . . . 202	10/25 (40%)	0.082
		18/25 (72%)
LRR: domain 5 of 19	203 . . . 226	9/25 (36%)	0.71
		16/25 (64%)
LRR: domain 6 of 19	227 . . . 250	11/25 (44%)	0.017
		19/25 (76%)
LRR: domain 7 of 19	251 . . . 274	7/25 (28%)	4.5
		18/25 (72%)
LRR: domain 8 of 19	299 . . . 322	9/25 (36%)	68
		17/25 (68%)
LRR: domain 9 of 19	323 . . . 344	9/25 (36%)	0.25
		18/25 (72%)
LRRCT: domain 1 of 1	354 . . . 402	20/55 (36%)	0.0078
		34/55 (62%)
LRRNT: domain 2 of 2	439 . . . 468	14/31 (45%)	0.047
		20/31 (65%)
LRR: domain 10 of 19	470 . . . 493	8/25 (32%)	41
		16/25 (64%)
LRR: domain 11 of 19	494 . . . 517	5/25 (20%)	0.35
		20/25 (80%)
LRR: domain 12 of 19	518 . . . 541	8/25 (32%)	0.22
		20/25 (80%)
LRR: domain 13 of 19	542 . . . 565	7/25 (28%)	11
		18/25 (72%)
LRR: domain 14 of 19	566 . . . 589	7/25 (28%)	1.4e+02
		15/25 (60%)
LRR: domain 15 of 19	590 . . . 613	5/25 (20%)	1.8
		19/25 (76%)
LRR: domain 16 of 19	614 . . . 637	9/25 (36%)	0.0028
		21/25 (84%)
LRR: domain 17 of 19	638 . . . 661	9/25 (36%)	38
		15/25 (60%)
LRR: domain 18 of 19	663 . . . 686	5/25 (20%)	84
		17/25 (68%)
LRR: domain 19 of 19	714 . . . 735	8/25 (32%)	0.91
		18/25 (72%)

Example 16

[0351] 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:59	2800 bp
NOV16a,	TAGACGCGGAGCCCAAGGAGGTAAAATGCACACTTGCTGCCCCCCAGTAACTTTGGAA
CG92715-01 DNA	CAGGACCTTCACAGAAAAATGCATAGCTGGATGCTGCAGACTCTAGCGTTTGCTGTAA
Sequence	CATCTCTCGTCCTTTCGTGTGCAGAAACCATCGATTATTACGGGGAAATCTGTGACAA
	TGCATGTCCTTGTGAGGAAAAGGACGGCATTTTAACTGTGAGCTGTGAAAACCGGGGG
	ATCATCAGTCTCTCTGAAATTAGCCCTCCCCGTTTCCCAATCTACCACCTCTTGTTGT
	CCGGAAACCTTTTGAACCGTCTCTATCCCAATGAGTTTGTCAATTACACTGGGGCTTC
	AATTTTGCATCTAGGTAGCAATGTTATCCAGCACATTGAGACCGGGGCTTTCCATGGG
	CTACGGGGTTTGAGGAGATTGCATCTAAACAATAATAAACTGGAACTTCTGCGAGATG
	ATACCTTCCTTGGCTTGGAGAACCTGGAGTACCTACAGGTCGATTACAACTACATCAG
	CGTCATTGAACCCAATGCTTTTGGGAAACTGCATTTGTTGCAGGTGCTTATCCTCAAT
	GACAATCTTTTGTCCAGTTTACCCAACAATCTTTTCCGTTTTGTGCCCTTAACGCACT
	TGGACCTCCGGGGGAACCGGCTGAAACTTCTGCCCTACGTGGGCCTCTTGCACCACAT
	GGATAAAGTTGTGGAGCTACAGCTGGAGGAAAACCCTTGGAATTGTTCTTGTGAGCTG
	ATCTCTCTAAAGGATTGGTTGGACAGCATCTCCTATTCAGCCCTGGTGGGGGATGTAG
	TTTGTGAGACCCCCTTCCGCTTACACGGAAGGGACTTGGACGAGGTATCCAAGCAGGA
	ACTTTGCCCAAGGAGACTTATTTCTGACTACGAGATGAGGCCGCAGACGCCTTTGAGC
	ACCACGGGGTATTTACACACCACCCCGGCGTCAGTGAATTCTGTGGCCACTTCTTCCT
	CTGCTGTTTACAAACCCCCTTTGAAGCCCCCTAAGGGGACTCGCCAACCCAACAAGCC
	CAGGGTGCGCCCCACCTCTCGGCAGCCCTCTAAGGACTTGGGCTACAGCAACTATGGC
	CCCAGCATCGCCTATCAGACCAAATCCCCGGTGCCTTTGGAGTGTCCCACCGCGTGCT
	CTTGCAACCTGCAGATCTCTGATCTGGGCCTCAACGTAAACTGCCAGGAGCGAAAGAT
	CGAGAGCATCGCTGAACTGCAGCCCAAGCCCTACAATCCCAAGAAAATGTATCTGACA
	GAGAACTACATCGCTGTCGTGCGCAGGACAGACTTCCTGGAGGCCACGGGGCTGGACC
	TCCTGCACCTGGGGAATAACCGCATCTCGATGATCCAGGACCGCGCTTTCGGGGATCT
	CACCAACCTGAGGCGCCTCTACCTGAATCGCAACAGGATCGAGAGGCTGAGCCCGGAG
	TTATTCTATGGCCTGCAGAGCCTGCAGTATCTCTTCCTCCAGTACAATCTCATCCGCG
	AGATTCAGTCTGGAACTTTTGACCCGGTCCCAAACCTCCAGCTGCTATTCTTGAATAA
	CAACCTCCTGCAGGCCATGCCCTCAGGCGTCTTCTCTGGCTTGACCCTCCTCAGGCTA
	AACCTGAGGAGTAACCACTTCACCTCCTTGCCAGTGAGTGGAGTTTTGGACCAGCTGA
	AGTCACTCATCCAAATCGACCTGCATGACAATCCTTGGGATTGTACCTGTGACATTGT
	GGGCATGAAGCTGTGGGTGGAGCAGCTCAAAGTGGGCGTCCTAGTGGACCAGGTGATC
	TGTAAGGCGCCCAAAAAATTCGCTGAGACCGACATGCGCTCCATTAAGTCGGAGCTGC
	TGTGCCCTGACTATTCAGATGTAGTAGTTTCCACGCCCACACCCTCCTCTATCCAGCT
	CCCTGCGAGGACCAGCGCCGTGACTCCTGCGGTCCGGTTGAATAGCACCGGGGCCCCC
	GCGAGCTTGGGCGCAGGCGGAGGGGCGTCGTCGGTGCCCTTGTCTGTGTTAATTCTCA
	GCCTCCTGCTGGTTTTCATCATGTCCGTCTTCGTGGCCGCCGGGCTCTTCGTGCTGGT
	CATGAAGCGCAGGAAGAAGAACCAGAGCGACCACACCAGCACCAACAACTCCGACGTG
	AGCTCCTTTAACATGCAGTACAGCGTGTACGGCGGCGGCGGCGGCACGGGCGGCCACC
	CACACGCGCACGTGCATCACCGCGGGCCCGCGCTGCCCAAGGTGAAGACGCCCGCGGG
	CCACGTGTATGAATACATCCCCCACCCACTGGGCCACATGTGCAAAAACCCCATCTAC
	CGCTCCCGAGAGGGCAACTCCGTAGAGGATTACAAAGACCTGCACGAGCTCAAGGTCA
	CCTACAGCAGCAACCACCACCTGCAGCAGCAGCAGCAGCCGCCGCCGCCACCGCAGCA
	GCCACAGCAGCAGCCCCCGCCGCAGCTGCAGCTGCAGCCTGGGGAGGAGGAGAGGCGG
	GAAAGCCACCACTTGCGGAGCCCCGCCTACAGCGTCAGCACCATCGAGCCCCGGGAGG
	ACCTGCTGTCGCCGGTGCAGGACGCCGACCGCTTTTACAGGGGCATTTTAGAACCAGA
	CAAACACTGCTCCACCACCCCCGCCGGCAATAGCCTCCCGGAATATCCCAAATTCCCG
	TGCAGCCCCGCTGCTTACACTTTCTCCCCCAACTATGACCTGAGACGCCCCCATCAGT
	ATTTGCACCCGGGGGCAGGGGACAGCAGGCTACGGGAACCGCTGCTCTACAGCCCCCC
	GAGTGCTGTCTTTGTA
	ORF Start: ATG at 26	ORF Stop: end of sequence
	SEQ ID NO:60	925 aa	MW at 103516.1 kD
NOV16a,	MHTCCPPVTLEQDLHRKNHSWMLQTLAFAVTSLVLSCAETIDYYGEICDNACPCEEKD
CG92715-01	GILTVSCENRGIISLSEISPPRFPIYHLLLSGNLLNRLYPNEFVNYTGASILHLGSNV
Protein Sequence	IQDIETGAFHGLRGLRRLHLNNNKLELLRDDTFLGLENLEYLQVDYNYISVIEPNAFG
	KLHLLQVLILNDNLLSSLPNNLFRFVPLTHLDLRGNRLKLLPYVGLLQHMDKVVELQL
	EENPWNCSCELISLKDWLDSISYSALVGDVVCETPFRLHGRDLDEVSKQELCPRRLIS
	DYEMRPQTPLSTTGYLHTTPASVNSVATSSSAVYKPPLKPPKGTRQPNKPRVRPTSRQ
	PSKDLGYSNYGPSIAYQTKSPVPLECPTACSCNLQISDLGLNVNCQERKIESIAELQP
	KPYNPKKMYLTENYIAVVRRTDFLEATGLDLLHLGNNRISMIQDRAFGDLTNLRRLYL
	NGNRIERLSPELFYGLQSLQYLFLQYNLIREIQSGTFDPVPNLQLLFLNNNLLQAMPS
	GVFSGLTLLRLNLRSNHFTSLPVSGVLDQLKSLIQIDLHDNPWDCTCDIVGMKLWVEQ
	LKVGVLVDEVICKAPKKFAETDMRSIKSELLCPDYSDVVVSTPTPSSIQVPARTSAVT
	PAVRLNSTGAPASLGAGGGASSVPLSVLILSLLLVFIMSVFVAAGLFVLVMKRRKKNQ
	SDHTSTNNSDVSSFNMQYSVYGGGGGTGGHPHAHVHHRGPALPKVKTPAGHVYEYIPH
	PLGHMCKNPIYRSREGNSVEDYKDLHELKVTYSSNHHLQQQQQPPPPPQQPQQQPPPQ
	LQLQPGEEERRESHHLRSPAYSVSTIEPREDLLSPVQDADRFYRGILEPDKHCSTTPA
	GNSLPEYPKFPCSPAAYTFSPNYDLRRPHQYLHPGAGDSRLREPVLYSPPSAVFV
	SEQ ID NO:61	4500 bp
NOV16b,	CGGAACCCGCGGTCGCCACCGCGGCGGCGGCCCCAGGCTGGAGGCCTCCGGGCGCCTC
CG92715-02 DNA	TTTCCTCCAGCCTCTGGGACTGCGCTGCTCGCAGTCTCCTCGCCCTGCCTGGGCTTGA
Sequence	GAAACCTAGTGCATACCCCAAAGAGGGTTTTTGTGTATGTGTGTGTTTTTAAACGGTG
	GCTATGATGACTGGGCCTTGGAGACGCGGAGACCAAGGAGGTAAAATGCACACTTGCT
	GCCCCCCAGTAACTTTGGAACAGGACCTTCACAGAAAAATGCATAGCTGGATGCTGCA
	GACTCTAGCGTTTGCTGTAACATCTCTCGTCCTTTCGTGTGCAGAAACCATCGATTAT
	TACGGGGAAATCTGTGACAATGCATGTCCTTGTGAGGAAAAGGACGGCATTTTAACTG
	TGAGCTGTGAAAACCGGGGGATCATCAGTCTCTCTGAAATTAGCCCTCCCCGTTTCCC
	AATCTACCACCTCTTGTTGTCCGGAAACCTTTTGAACCGTCTCTATCCCAATGAGTTT
	GTCAATTACACTGGGGCTTCAATTTTGCATCTAGGTAGCAATGTTATCCAGGACATTG
	AGACCGGGGCTTTCCATGGGCTACGGGGTTTGAGGAGATTGCATCTAAACAATAATAA
	ACTGGAACTTCTGCGAGATGATACCTTCCTTGGCTTGGAGAACCTGGAGTACCTACAG
	GTCGATTACAACTACATCAGCGTCATTGAACCCAATGCTTTTGGGAAACTGCATTTGT
	TGCAGGTGCTTATCCTCAATGACAATCTTTTGTCCAGTTTACCCAACAATCTTTTCCG
	TTTTGTGCCCTTAACGCACTTGGACCTCCGGGGGAACCGGCTGAAACTTCTGCCCTAC
	GTGGGGCTCTTGCAGCACATGGATAAAGTTGTGGAGCTACAGCTGGAGGAAAACCCTT
	GGAATTGTTCTTGTGAGCTGATCTCTCTAAAGGATTGGTTGGACAGCATCTCCTATTC
	AGCCCTGGTGGGGGATGTAGTTTGTGAGACCCCCTTCCGCTTACACGGAAGGGACTTG
	GACGAGGTATCCAAGCAGGAACTTTGCCCAAGGAGACTTATTTCTGACTACGAGATGA
	GGCCGCAGACGCCTTTGAGCACCACGGGGTATTTACACACCACCCCGGCGTCAGTGAA
	TTCTGTCGCCACTTCTTCCTCTGCTGTTTACAAACCCCCTTTGAAGCCCCCTAAGGGG
	ACTCGCCAACCCAACAAGCCCAGGGTGCGCCCCACCTCTCGGCACCCCTCTAAGGACT
	TGGGCTACAGCAACTATGGCCCCAGCATCGCCTATCAGACCAAATCCCCGGTGCCTTT
	GGAGTGTCCCACCGCGTGCTCTTGCAACCTGCAGATCTCTGATCTGGGCCTCAACGTA
	AACTGCCAGGAGCGAAAGATCGAGAGCATCGCTGAACTGCAGCCCAAGCCCTACAATC
	CCAAGAAAATGTATCTGACAGAGAACTACATCGCTGTCGTGCGCAGGACAGACTTCCT
	GGAGGCCACGGGGCTGGACCTCCTGCACCTGGGGAATAACCGCATCTCGATGATCCAG
	GACCGCGCTTTCGGGGATCTCACCAACCTGAGGCGCCTCTACCTGAATGGCAACAGGA
	TCGAGAGGCTGAGCCCGGAGTTATTCTATGGCCTGCAGAGCCTGCAGTATCTCTTCCT
	CCAGTACAATCTCATCCGCGAGATTCAGTCTGGAACTTTTGACCCGGTCCCAAACCTC
	CAGCTGCTATTCTTGAATAACAACCTCCTGCAGGCCATGCCCTCAGGCGTCTTCTCTG
	GCTTGACCCTCCTCAGGCTAAACCTGAGGAGTAACCACTTCACCTCCTTGCCAGTGAG
	TGGAGTTTTGGACCAGCTGAAGTCACTCATCCAAATCGACCTGCATGACAATCCTTGG
	GATTGTACCTGTGACATTGTGGGCATGAAGCTGTGGGTGGAGCAGCTCAAAGTGGGCG
	TCCTAGTGGACGAGGTGATCTGTAAGGCGCCCAAAAAATTCGCTGAGACCGACATGCG
	CTCCATTAAGTCGGAGCTGCTGTGCCCTGACTATTCAGATGTAGTAGTTTCCACGCCC
	ACACCCTCCTCTATCCAGGTCCCTGCGAGGACCAGCGCCGTGACTCCTGCGGTCCGGT
	TGAATAGCACCGGGGCCCCCGCGAGCTTGGGCGCAGGCGGAGGGGCGTCGTCGGTGCC
	CTTGTCTGTGTTAATTCTCAGCCTCCTGCTGGTTTTCATCATGTCCGTCTTCGTGGCC
	GCCGGGCTCTTCGTGCTGGTCATGAAGCGCAGGAAGAAGAACCAGAGCGACCACACCA
	GCACCAACAACTCCGACGTGAGCTCCTTTAACATGCAGTACAGCGTGTACGGCGGCGG
	CGGCGGCACGGGCGGCCACCCACACGCGCACGTGCATCACCGCGGGCCCGCGCTGCCC
	AAGGTGAAGACGCCCGCGGGCCACGTGTATGAATACATCCCCCACCCACTGGGCCACA
	TGTGCAAAAACCCCATCTACCGCTCCCGAGAGGGCAACTCCGTAGAGGATTACAAAGA
	CCTGCACGAGCTCAAGGTCACCTACAGCAGCAACCACCACCTGCAGCAGCAGCAGCAG
	CCGCCGCCGCCACCGCAGCAGCCACAGCAGCAGCCCCCGCCGCAGCTGCAGCTGCAGC
	CCGGGGAGGAGGAGAGGCGGGAAAGCCACCACTTGCGGAGCCCCGCCTACAGCGTCAG
	CACCATCGAGCCCCGGGAGGACCTGCTGTCGCCGGTGCAGGACGCCGACCGCTTTTAC
	AGGGGCATTTTAGAACCAGACAAACACTGCTCCACCACCCCCGCCGGCAATAGCCTCC
	CGGAATATCCCAAATTCCCGTGCAGCCCCGCTGCTTACACTTTCTCCCCCAACTATGA
	CCTGAGACGCCCCCATCAGTATTTGCACCCGGGGGCAGGGGACAGCAGGCTACGGGAA
	CCGGTGCTCTACAGCCCCCCGAGTGCTGTCTTTGTAGAACCCAACCGGAACGAATATC
	TCGAGTTAAAAGCAAAACTAAACGTTGAGCCGGACTACCTCGAAGTGCTGGAAAAACA
	GACCACGTTTAGCCAGTTCTAAAAGCAAAGAAACTCTCTTGGAGCTTTTGCATTTAAA
	ACAAACAAGCAAGCAGACACACACAGTGAACACATTTGATTAATTGTGTTGTTTCAAC
	GTTTAGGGTGAAGTGCCTTGGCACGGGATTTCTCAGCTTCGGTGGAAGATACGAAAAG
	GGTGTGCAATTTCCTTTAAAATTTACACGTGGGAAACATTTGTGTAAACTGGGCACAT
	CACTTTCTCTTCTTGCGTGTGGGGCAGGTGTGGAGAAGGGCTTTAAGGAGGCCAATTT
	GCTGCGCGGGTGACCTGTGAAAGGTCACAGTCATTTTTGTAGTGGTTGGAAGTGCTAA
	GAATGGTGGATGATGGCAGAGCATAGATTCTACTCTTCCTCTTTAGCTTCCTCCCCAT
	CCAACGAACCCTGCCCAACACTCTAAATATCCACCAGATAAGACATGGAATGAGGTCT
	AAATGACACAAAGTGAAGAAATCAACACAACACAAACTTTACAGCTAACAACAAATGA
	TCAACAAAAACCGAACCAACAAGACAACCATCGAACCTCACCACTCCACACTCACAAC
	AACTCATATCAAGACAACAACACAATGACGTTAAAGGAAACGAAATCAATGCAAAAAT
	AGACATTTGACAATACAAAAAAACAAGAACCGTGATCACACTACAACCGAAGCAACCA
	TAGATGTGAGAAAAAACAACAAACAAAACACCGAGCTATATGATCCATAATTGATTAG
	TCAAAATAACTTATTGATGAAATATACAAATATTTTATTGTAGCACCTATTTTTATAT
	GCACATTTAGCATTCCTCTTTCCTTCACTATTTAGCCTATGATTTTGCAGAGGTGTCA
	CACTGTATTAGGATCTGCATTTCTAAAACTGACGTGGTATCAGGAAGGCATTTTCAAT
	CATTCAAAATGTGGAGAATTTAATGGCTAAATCTTTAAAAGCCAATGCAACCCACCCA
	ATTGAATCTGCATTTTCTTTTAAGAAAACAGAGCTGATTGTATCCCAATGTATTTTAA
	AAAATAGGGCAATTGATTGGGCCATTCCGAGAGAATTGTTTGCAAGTTTTGGGTTTTA
	TTAGAAAATATTTGAAAGTATTTTTATTAATGAACCAAAATGACATGTTCATTTGACT
	ACTATTGTAGCCGATTTTCGATTGTTTAACCAAACCCAGTTGCATTTGTACAGATCCA
	CGTGTACTGGCACCTCAGAAGACCAAATCATGGACTGTACAAGTCTCTATACAATGTC
	TTTATCCCTGTGGGCAGCAAGCAATGATGATAATGACAAACAGGATATCTGTAAGATG
	GGGCTACTGTTGTTACAGTCTCATATGTATCCCAGCACATGTAATTTTTTAAATAGTT
	TCTGAATAAACACTTGATAACTATGTCAAAAAAA
	ORF Start: ATG at 178	ORF Stop: TAA at 3094
	SEQ ID NO: 62	972 aa	MW at 109043.3 kD
NOV16b,	MMTGPWRRGDQGGKMHTCCPPVTLEQDLHRKMHSWMLQTLAFAVTSLVLSCAETIDYY
CG92715-02	GEICDNACPCEEKDGILTVSCENRGIISLSEISPPRFPIYHLLLSGNLLNRLYPNEFV
Protein Sequence	NYTGASILHLCSNVIQDIETGAFHGLRGLRRLHLNNNKLELLRDDTFLGLENLEYLQV
	DYNYISVIEPNAFGKLHLLQVLILNDNLLSSLPNNLFRFVPLTHLDLRGNRLKLLPYV
	GLLQHMDKVVELQLEENPWNCSCELISLKDWLDSISYSALVGDVVCETPFRLHGRDLD
	EVSKQELCPRRLISDYEMRPQTPLSTTGYLHTTPASVNSVATSSSAVYKPPLKPPKGT
	RQPNKPRVRPTSRQPSKDLGYSNYGPSIAYQTKSPVPLECPTACSCNLQISDLGLNVN
	CQERKIESIAELQPKPYNPKKMYLTENYIAVVRRTDFLEATGLDLLHLGNNRISMIQD
	RAFGDLTNLRRLYLNGNRIERLSPELFYGLQSLQYLFLQYNLIREIQSGTFDPVPNLQ
	LLFLNNNLLQANPSGVFSGLTLLRLNLRSNHFTSLPVSGVLDQLKSLIQIDLHDNPWD
	CTCDIVGMKLWVEQLKVGVLVDEVICKAPKKFAETDMRSIKSELLCPDYSDVVVSTPT
	PSSIQVPARTSAVTPAVRLNSTGAPASLGAGGGASSVPLSVLILSLLLVFIMSVFVAA
	GLFVLVNKRRKKNQSDHTSTNNSDVSSFNMQYSVYGGGGGTGGHPHAHVHHRGPALPK
	VKTPAGHVYEYIPHPLGHMCKNPIYRSREGNSVEDYKDLHELKVTYSSNHHLQQQQQP
	PPPPQQPQQQPPPQLQLQPGEEERRESHHLRSPAYSVSTIEPREDLLSPVQDADRFYR
	GILEPDKHCSTTPAGNSLPEYPKFPCSPAAYTFSPNYDLRRPHQYLHPGAGDSRLREP
	VLYSPPSAVFVEPNRNEYLELKAKLNVEPDYLEVLEKQTTFSQF

[0352] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 16B.

TABLE 16B
Comparison of NOV16a against NOV16b.
	Protein	NOV16a Residues/	Identities/Similarities
	Sequence	Match Residues	for the Matched Region
	NOV16b	1 . . . 925	752/925 (81%)
		15 . . . 939	752/925 (81%)

[0353] Further analysis of the NOV16a protein yielded the following properties shown in Table 16C.

TABLE 16C
Protein Sequence Properties NOV16a
PSort     0.8500 probability located in
analysis: endoplasmic reticulum (membrane); 0.4400
          microbody (peroxisome); 0.3000 probability located in
          nucleus
SignalP   Cleavage site between residues 41 and 42
analysis:

[0354] 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
AAB95753	Human protein sequence SEQ ID	1 . . . 925	925/925 (100%)	0.0
	NO: 18665 - Homo sapiens, 958 aa.	1 . . . 925	925/925 (100%)
	[EP1074617-A2, 07-FEB-2001]
ABB12025	Human IGFALS homologue, SEQ	1 . . . 925	924/925 (99%)	0.0
	ID NO: 2395 - Homo sapiens,	20 . . . 944	924/925 (99%)
	977 aa. [WO200157188-A2,
	09-AUG-2001]
AAG67524	Amino acid sequence of a human	46 . . . 925	423/886 (47%)	0.0
	secreted polypeptide - Homo sapiens,	27 . . . 812	563/886 (62%)
	845 aa. [WO200166690-A2,
	13-SEP-2001]
AAE01232	Human gene 1 encoded secreted	46 . . . 925	422/886 (47%)	0.0
	protein HMIAJ30, SEQ ID NO: 94 -	27 . . . 812	562/886 (62%)
	Homo sapiens, 845 aa.
	[WO200134769-A2, 17-MAY-2001]
AAE01312	Human gene 1 encoded secreted	46 . . . 630	336/594 (56%)	0.0
	protein fragment, SEQ ID NO: 177 -	6 . . . 583	436/594 (72%)
	Homo sapiens, 596 aa.
	[WO200134769-A2, 17-MAY-2001]

[0355] 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
O94991	Hypothetical protein KIAA0918 -	1 . . . 925	925/925 (100%)	0.0
	Homo sapiens (Human), 966 aa	9 . . . 933	925/925 (100%)
	(fragment).
Q9H156	BG115M3.1 (NOVEL PROTEIN) -	46 . . . 925	423/886 (47%)	0.0
	Homo sapiens (Human), 845 aa.	27 . . . 812	563/886 (62%)
O94933	Hypothetical protein KIAA0848 -	9 . . . 773	370/787 (47%)	0.0
	Homo sapiens (Human), 977 aa.	4 . . . 764	511/787 (64%)
Q96JH3	KIAA1854 PROTEIN - Homo	46 . . . 599	325/555 (58%)	0.0
	sapiens (Human), 572 aa (fragment).	33 . . . 571	419/555 (74%)
CAB65788	BG256O22.1 (SIMILAR TO IGFALS	16 . . . 713	348/703 (49%)	0.0
	(INSULlN-LIKE GROWTH	15 . . . 683	468/703 (66%)
	FACTOR BINDING PROTEIN,
	ACID LABILE SUBUNIT)) - Homo
	sapiens (Human), 853 aa (fragment).

[0356] PFam analysis indicates that the NOV16a protein contains the domains shown in Table 16F.

TABLE 16F
Domain Analysis of NOV16a
		Identities/
		NOV16a	Similarities
	Match	for the	Expect
Pfam Domain	Region	Matched Region	Value
LRRNT: domain 1 of 2	47 . . . 82	12/37 (32%)	23
		23/37 (62%)
LRR: domain 1 of 10	82 . . . 105	9/25 (36%)	4.8e+02
		13/25 (52%)
LRR: domain 2 of 10	106 . . . 129	5/25 (20%)	80
		16/25 (64%)
LRR: domain 3 of 10	130 . . . 153	9/25 (36%)	1.6
		19/25 (76%)
LRR: domain 4 of 10	154 . . . 177	10/25 (40%)	0.0061
		21/25 (84%)
LRR: domain 5 of 10	178 . . . 200	9/25 (36%)	43
		16/25 (64%)
LRR: domain 6 of 10	201 . . . 222	10/25 (40%)	48
		17/25 (68%)
LRRCT: domain 1 of 2	235 . . . 285	18/54 (33%)	3e−08
		34/54 (63%)
LRRNT: domain 2 of 2	373 . . . 406	10/35 (29%)	0.049
		19/35 (54%)
LRR: domain 7 of 10	434 . . . 457	9/25 (36%)	0.17
		17/25 (68%)
LRR: domain 8 of 10	458 . . . 481	10/25 (40%)	0.00064
		22/25 (88%)
LRR: domain 9 of 10	482 . . . 505	6/25 (24%)	0.096
		18/25 (72%)
LRR: domain 10 of 10	506 . . . 529	10/25 (40%)	0.0085
		19/25 (76%)
LRRCT: domain 2 of 2	563 . . . 613	12/54 (22%)	5.6e−05
		38/54 (70%)

Example 17

[0357] 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: 63	15603 bp
NOV17a,	CTAATAGAATTCAGCGGCCGCTTTCCCCGGTGCGCAGTTGTGCTTGGACGTTTGTTCC
CG92813-01 DNA	TCCCTCTTCACGCTCTTCGCTGCGGGTAAGTTCTAAAGTTTCTGAAGGCCGTTCTTTG
Sequence	CAATGATTCCTCATATACCTTAGATACAGGCAACTTCTCCCAACTCTCATCCACCCGC
	GTGAAAACGCTCAGACTATCTGGATTCAAAAACAAAGTAAAAGGGGGCATATATAAGA
	GGCTTGAGAAACTTTTCTGGGAACTCAGCTCACAGGAGTGTCCCGCGGAATGCCCTGC
	CGCTTTTCGCCACAGCATCTCTCTTGCACTCCGCGTTCAACTGGCTACCTAGAGTCTT
	TTGCTGATGCTACTTGCTTTTGCCGGACTGGACGTTCTTTGAAATAGCAGAGGTCTCA
	GACCAAGCCGTCAGCTGAATCTTTGCTGGCGCTCCTTAATCCCTGTAAATATCATTCC
	GTTTGCTTCACCCCTTCCTTCTCTTTATCACATCGTTTTAGGGAGCCAGGACCATGGA
	CTTAGCACCAGACAGGGCTACTGGCCGCCCGTGGCTCCCGTTGCACACTCTATCAGTA
	TCTCAGCTCCTTCGAGTGTTTTGGCTACTGTCATTGCTTCCGGGGCAGGCCTGGGTCC
	ACGGGGCCGAGCCGCGCCAGGTGTTCCAAGTGCTGGAAGAGCAACCTCCAGGCACTCT
	GGTAGGCACCATCCAGACGCGCCCCGGCTTCACCTACAGGCTCAGCGAAAGCCACGCC
	CTGTTTGCCATAAACAGTAGCACCGGAGCCCTGTACACCACCTCCACCATCGACCGCG
	AGAGCCTGCCCAGCGACGTGATCAACCTGGTGGTCCTTTCCAGCGCGCCCACCTACCC
	CACCGAAGTGCGAGTGCTGGTGCGGGACCTCAATGACAACGCCCCCGTTTTCCCGGAC
	CCCTCTATCGTGGTCACTTTCAAGGAAGACAGTAGCAGCGGACGCCAAGTCATCTTAG
	ACACCGCCACCGACTCGGACATCGGCTCAAACGGTGTGGACCACCGCTCCTACCGCAT
	CATCCGCGGCAATGAGGCGGGGCGCTTCCGTCTGGACATCAACCTGAACCCGAGCGGC
	GAGGGAGCGTTCCTGCATCTGGTGTCCAAGGGCGGACTGGACCGTGAGGTCACTCCGC
	AGTACCAGCTCCTGGTTGAGGTGGAGGACAAGGGTGAGCCTAAGCGGCGGGGCTACCT
	TCAGGTAAACGTGACTGTGCAAGACATTAATGACAACCCCCCGGTTTTTGGCAGTTCT
	CACTACCAGCCCGGGGTGCCTGAGGACGCGGTTGTGGGTTCCAGCGTCCTCCAGGTGG
	CGGCGGCGGACGCGGACGAGGGCACCAACGCGGACATCCGCTATCGCCTGCAGGACGA
	GGGGACCCCCTTCCAAATGGACCCTGAGACGGGACTTATCACGGTCCGCGAGCCCCTG
	GACTTCGAAGCTCGGCGCCAATACTCGCTTACGGTGCAGGCGATGCACAGACGCGTGC
	CTTCCCTCACTGGGCGCGCCGAGGCGCTGATTCAGCTGCTGGACGTGAATGACAATGA
	CCCGGTAGTGAAGTTCCGCTACTTCCCGGCCACCTCGCGCTACCCCTCGGTAGATGAG
	AATGCTCAAGTGGGCACCGTGGTGGCTCTGCTCACCGTGACGGACGCAGATTCTCCCG
	CGGCCAACGGGAACATCTCCGTGCAAATTCTCGGGGGCAATGAGCAGCGCCACTTTGA
	AGTGCAAAGCAGCAAAGTGCCGAACCTGAGCCTAATCAAGGTGGCCAGCGCCTTGGAC
	CGCGAGCGCATCCCTTCCTACAACCTCACAGTTTCCGTCTCTGATAACTACGGGGCGC
	CCCCTGGCGCAGCAGTCCAGGCGCGCTCTTCTGTGGCAAGCCTGGTGATTTTTGTTAA
	TGACATCAATGACCATCCTCCTGTCTTTTCACAGCAAGTGTACACAGTGAACCTGAGC
	GAGGAGGCGCCTCCGGGAAGCTATGTGAGTGGGATATCTGCCACTGATGGCGACTCTG
	GTCTCAATGCTAATCTGCGTTACAGCATTGTCTCTGGCAATGGACTGGGATGGTTCCA
	TATCAGTGAACATAGCGGCCTCGTGACCACTGGGTCCTCTGGGGGCCTGGACCGTGAA
	CTTGCTTCCCAGATTGTTCTGAATATAAGTGCCCGGGACCAGGGAGTTCACCCCAAGG
	TGTCCTATGCCCAGCTTGTAGTAACTCTCCTAGATGTCAATGATGAAAAGCCAGTATT
	TAGCCAGCCAGAAGGGTATGATGTGTCTGTGGTTGAGAATGCCCCAACAGGGACAGAA
	CTGTTGATGCTCAGGGCAACTGACGGGGACCTGGGTGACAACGGAACAGTGCGCTTCT
	CCTTACAAGAGGCAGAGACTGACCGGAGGTCCTTCCGTCTGGATCCTGTGTCTGGGAG
	GTTGAGTACTATTTCCTCCTTGGACAGAGAAGAGCAAGCCTTCTACTCCCTGTTGGTT
	CTGGCCACAGATCTGGGCTCCCCTCCCCAGTCATCAATGGCTCGCATAAATGTGAGTC
	TTCTGGATATAAATGATAACAGCCCTGTCTTCTACCCGGTCCAATACTTTGCTCACAT
	TAAGGAGAATGAGCCTGGAGGTAGCTACATCACCACTGTGTCTGCCACTGACCCAGAC
	TTGGGTACCAATGGTACTGTCAAATATAGCATATCTGCTGGGGACAGGTCTCGGTTTC
	AGGTCAATGCTCAGAGTGGGGTTATTTCTACAAGAATGGCCCTAGACAGAGAAGAAAA
	AACAGCTTATCAGTTGCAAATAGTAGCTACTGATGGTGGCAATTTACAATCTCCCAAC
	CAGGCAATAGTAACCATCACTGTATTGGACACTCAAGACAACCCACCTGTATTCAGTC
	AGGTTGCCTACAGCTTTGTGGTTTTTGAGAACGTGGCGCTGGGATATCATGTGGGTAG
	TGTGTCTGCATCCACCATGGATCTCAATTCCAACATCAGTTATCTCATTACTACTGGG
	GATCAGAAAGGTATGTTTGCTATCAACCAGGTCACTGGGCAGCTTACCACAGCAAATG
	TGATTGATAGAGAAGAGCAATCCTTTTATCAGCTGAAGGTAGTGGCCAGTGGGGGCAC
	AGTGACTGGAGACACTATGGTTAACATAACAGTTAAGGATTTGAATGACAACTCTCCC
	CATTTCCTTCAGGCAATAGAGAGTGTAAATGTGGTGGAGAATTGGCAGGCAGGTCACA
	GCATTTTCCAGGCCAAAGCTGTGGACCCTGATGAAGGTGTCAATGGCATGGTACTCTA
	TAGTCTGAAGCAAAACCCCAAGAACCTGTTTGCTATCAATGAAAAGAATGGCACTATT
	AGTCTGCTTGGGCCCCTGGATGTTCATGCTGGCTCCTACCAAATAGAGATCTTGGCAT
	CTGACATGGGTGTCCCACAGCTCTCCTCTAGTGTCATCCTAACAGTTTATGTCCATGA
	TGTAAATGACAATTCACCAGTGTTTGACCAACTCTCTTATGAAGTCACCCTTTCTGAG
	TCAGAACCTGTGAATTCTCGATTCTTTAAAGTACAAGCTTCTGATAAGGATTCAGGAG
	CAAATGATGGTCAATTGTATATAAAAAGTGAACTGGACCGTGAACTTCAAGACAGATA
	TGTTTTAATGGTTGTTGCTTCTGACAGAGCAGTGGAACCCCTTAGTGCTACTGTGAAT
	GTTACTGTAATTTTAGAAGATGTAAATGATAACAGACCTCTTTTTAACAGTACCAATT
	ACACATTTTACTTCGAAGAAGAGCAGAGGGCTGGGTCGTTTGTGGGCAAAGTAAGTGC
	TGTAGATAAAGACTTTGGGCCAAATGGAGAAGTAAGGTATTCTTTTGAAATGGTGCAG
	CCAGATTTTGAGTTGCATGCCATCAGTGGGGAAATTACAAATACTCATCAGTTTGACA
	GGGAGTCTCTTATGAGGCGGAGAGGGACTGCTGTGTTTAGCTTTACAGTCATAGCAAC
	AGATCAGGGGATCCCTCAGCCTCTCAAGGATCAGGCCACTGTACATGTTTACATGAAG
	GATATAAATGATAATGCTCCCAAATTTTTAAAAGACTTTTACCAAGCTACAATATCAG
	AATCAGCAGCCAATCTGACACAAGTGTTAAGAGTATCTGCCTCAGATGTTGATGAAGG
	TAATAATGGACTTATTCACTATTCTATAATAAAAGGAAATGAAGAAAGACAGTTTGCT
	ATAGACAGTACCTCTGGTCAGGTAACACTAATTGGCAAATTAGACTATGAAGCAACAC
	CTGCCTATTCCCTTGTAATTCAAGCAGTGGATTCAGGGACAATCCCCCTCAATTCAAC
	GTGTACTTTAAATATTGATATTTTAGATGAAAATCACAATACCCCTTCTTTCCTTAAA
	TCAACACTGTTTGTTGATGTTTTGGAAAACATGAGAATTGGTGAACTCGTGTCCTCTG
	TTACTGCAACTGATTCCGATTCAGGTGACAATGTTGATTTATATTACAGTATTACTGG
	GACTAACAACCACGGAACTTTTAGCATTAGCCCAAACACTGGGAGTATTTTTCTTCCC
	AAAAAACTGGACTTTGAAACACAGTCTTTGTATAAATTAAATATAACAGCAAAAGACC
	AAGGAAGACCTCCTCGTTCATCTACAATGTCAGTGGTTATTCACGTGAGGGACTTTAA
	TGACAATCCTCCTAGCTTTCCTCCTGGAGATATTTTCAAGTCTATTGTTGAGAACATT
	CCCATTGGTACATCTGTCATTTCAGTGACTGCACATGACCCTGATGCAGACATTAATG
	GTCAACTATCCTACACAATCATTCAACAGATGCCAAGAGGCAACCACTTTACCATAGA
	TGAAGTCAAAGGGACTATATATACTAATGCTGAAATAGATCGGGAATTTGCTAATCTC
	TTTGAGTTGACTGTAAAAGCCAATGATCAAGCTGTGCCAATAGAAACTAGACGGTATG
	CTTTGAAGAACGTGACCATTTTGGTTACAGACCTCAATGACAATGTCCCAATGTTTAT
	ATCACAAAACGCCCTTGCTGCAGACCCATCAOCTGTGATTGGTTCCGTTCTGACAACA
	ATTATGGCTGCTGACCCAGATGAAGGTGCTAATGGAGAAATAGAGTATGAGATCATCA
	ATGGGGACACAGACACCTTCATTGTTGATCGTTATAGTGGAGACCTGAGAGTGGCTTC
	AGCGTTGGTGCCTTCACAGTTGATCTACAATCTCATAGTTTCAGCAACAGACCTTGGG
	CCTGAAAGGAGGAAATCGACCACTGAATTGACCATCATTCTTCAGGGCCTTGATGGAC
	CTGTTTTTACTCAACCCAAATATATAACTATTTTGAAGGAAGGAGAACCCATTGGCAC
	AAACGTGATATCAATAGAAGCAGCTAGCCCCAGAGGATCTGAGGCCCCAGTGGAGTAT
	TATATTGTTTCAGTTCGTTGTGAAGAAAAAACTGTTGGACGCCTCTTTACTATTGGAC
	GACATACTGGTATAATTCAGACCGCAGCCATTCTGGACCGGGAGCAAGGAGCATGTCT
	TTACCTGGTGGATGTTTATGCCATAGAAAAATCAACTGCTTTTCCCAGAACACAGAGA
	GCAGAGGTAGAAACAACACTTCAGGATATCAATGACAATCCACCAGTATTTCCAACGG
	ACATGCTGGATCTCACGGTAGAGGAGAACATTGGAGATGGCTCTAAGATTATGCAGCT
	GACAGCCATGGATGCTGACGAGGTGCAAATGCTCTCGTCACATACACTATCATTAGTG
	GGTTCTTTGGTAGCAGCCATTTTAGCCACGGATGATGACTCTGGTGTGAATGGAGAAA
	TTACATATATTGTGAATGAAGATGATGAAGATGGCATCTTTTTCCTGAATCCTATTAC
	TGGGCTCTTTAATTTGACTCGATTATTAGATTATGAAGTACAGCAATATTATATCCTC
	ACTGTTCGAGCAGAAGATGGTGGGGGACAATTTACTACCATCAGAGTTTATTTCAATA
	TTCTAGATGTAAATGATAATCCACCTATTTTCAGCTTGAATTCATACAGCACATCTTT
	AATGGAGAATCTACCTGTGGGATCTACTGTTCTTGTGTTTAATGTTACTGATGCAGAT
	ATGATGAAGGCAGAAATAAAGATGTTCTTTGAAACCAGTGAGAACAAAGACACAACAT
	ACCAGAATCTCTGGGACACATTCAAAGCAGTGTGTAGAGGGAAATTTATAGCACTAAA
	TCCCCACAAGAGAAAGCAGGAAAGATCCAAAATTGACACCCTAACATCACAATTAAAA
	GAACTAGAAAAGCAAGAGCAAACACATTCAAAAGCTAGCAGAAGGCAAGAAATAACTA
	AAATCAGAGCAGAACTGAAGGATATAGAGACACAAAAAACCCTTCAAAAAATTAATGA
	ATCCAGGAGCTGGTTTTTTGAAAGGATCAACAAAATTGATAGACCGCTAGCAAGACTA
	ATAAAGAAGAAAACAGAGAAGAATCAAATAGACGCAATAAAAAATGATAAAGGGGATA
	TCACCATCGATCCCACAGAAATACAAACTACCATCAGAGAATACTGCAAACACCTCTA
	TGCAAATAAACTAGAAAATCTAGAAGAAATGGATAAATTCCTCGACACATACACCCTC
	CCAAGACTAAACCAGGAAGAAGTTGAATCTCTGAATAGACCAATAACAGACTCTGAAA
	CTGTGGCAATAATCAATAGCTTACCAACCAAAAAGAGTCCAGCACCAGATGCATTCAC
	AGCCGAATTCTACCAGATGATAACAACCCCAGTCTTTGCACAAGCTTTGTATAAAGTG
	GAGATTAATGAAAACACACTTACTGGAACAGATATAATACAAGTGTTCGCAGCAGATG
	GAGATGAAGGCACAAATGGACAGGTTCGCTATGGCATTGTTAATGGTAATACCAATCA
	GGAATTTCGGATAGACTCTGTCACAGGTGCCATCACTGTCGCTAAACCTTTGGATAGA
	GAAAAGACCCCTACCTACCATTTAACTGTTCAGGCAACAGATCGAGGCAGCACACCCA
	GAACTGATACCTCCACGGTCAGCATTGTTCTACTGGATATTAATGACTTTGTTCCTGT
	ATTTGAGCTATCTCCATATTCTGTAAATGTCCCTGAGAATTTAGGGACACTACCCAGA
	ACAATTCTTCAGACTGCTTCGCCTTGCGTGAGGTTTGCCAGCGCCAGTAAAGCGTATT
	TCACAACAATTCCTGACGATGCACCAACTGGAACAGATGTTTTATTGGTAAATGCCTC
	ACATGCTGATGCTTCAAAGAATGCAGTTATAAGTTATAGGATCATCGGTGGAAACTCT
	CAGTTCACGATCAACCCATCGACAGGACAAATCATCACCAGCGCATTGTTAGATAGGG
	AAACAAAAGATAATTATACTTTGGTAGTGGTCTGCAGTGATGCGGGATCCCCAGAGCC
	TCTTTCCAGTTCCACCAGTGTGCTTGTCACTGTGACTGATGTCCATGACAATCCACCA
	AGATTTCAGCATCACCCATATGTCACTCACATCCCATCTCCTACTCTTCCACGTTCCT
	TTGTCTTTGCGGTTACAGTCACAGATGCTGATATTGGACCAAATTCTGAACTGCATTA
	TTCTCTTTCGGGTAGAAATTCTGAAAAATTTCACATTGACCCACTGAGGGGAGCCATT
	ATGGCCGCCGGACCACTAAACGGAGCTTCAGAAGTGACATTTTCTGTGCATGTAAAAG
	ATGGTGGCTCATTTCCAAAGACAGATTCTACAACAGTGACTGTTAGATTCGTGAATAA
	GGCCGATTTCCCTAAAGTCAGAGCCAAAGAACAAACGTTCATGTTTCCTGAAAACCAA
	CCAGTCAGCTCTCTTGTCACCACCATCACAGGATCCTCTTTAAGAGGAGAACCTATGT
	CATATTATATCGCAAGTGGGAATCTTGGCAATACTTTCCAGATTGATCAGTTAACAGG
	GCAGGTGTCTATTAGTCAACCTCTGGATTTTGAAAAGATACAAAAATATCTTGTATGG
	ATAGACGCCAGAGACGGTGGTTTCCCTCCTTTCTCCTCTTACGAGAAACTTGATATAA
	CAGTATTAGATGTCAATGATAATGCCCCAATTTTTAAGGAAGACCCATTTATATCTGA
	AATATTGGAAAACCTTTCCCCTCGAAAAATACTTACTGTTTCGGCAATGGACAAGGAC
	AGTGGACCCAATGGACAGTTAGATTATGAAATTGTTAATGGCAACATGGAAAATAGTT
	TCAGTATCAATCATGCTACTGGTGAAATTAGAAGCGTTAGACCTTTGGACAGGGAAAA
	AGTATCTCATTATGTCCTAACCATAAAATCATCAGACAAAGGGTCCCCGTCTCAGAGT
	ACTTCAGTAAAAGTCATGATTAACATTTTAGATGAAAATGATAATGCCCCTAGGTTTT
	CTCAGATATTTAGTGCCCATGTTCCTGAAAATTCCCCCTTAGGATACACAGTTACCCG
	TGTCACAACTTCTGATGAAGACATTGGGATCAATGCAATTAGTAGATATTCTATAATG
	GATGCAAGTCTTCCATTTACAATTAATCCCAGCACAGGGGATATTCTCATAAGCAGAC
	CTTTAAATAGGGAAGATACAGACCGTTACAGAATTCGAGTTTCCGCACATGATTCTGG
	GTGGACTGTAAGTACAGATGTCACAATATTTGTGACAGACATCAATGACAATGCTCCA
	AGATTTAGCAGAACTTCCTATTATTTAGATTGCCCTGAACTTACTGAGATTGGCTCCA
	AAGTAACTCAGGTATTTGCAACAGATCCTGATGAGGGATCAAATGGACAAGTGTTTTA
	TTTCATAAAATCCCAATCAGAATATTTCAGGATTAATGCCACCACTGGAGAGATTTTC
	AATAAACAGATCTTAAAATACCAAAATGTCACTGGCTTCAGTAATGTGAATATCAACA
	GGCATAGTTTTATAGTGACATCTTCAGATCGAGGTAAACCTTCCTTAATTAGTGAGAC
	AACAGTTACCATCAATATAGTGGACAGTAATGACAATGCACCTCAATTTCTTAAAAGT
	AAATATTTCACTCCAGTCACCAAAAATGTTAAGGTTGGTACGAAGTTAATCAGAGTTA
	CAGCAATAGATGACAAAGATTTTGGACTGAATTCAGAAGTGGAGTATTTCATTTCTAA
	TGATAACCATTTAGGAAAATTTAAGTTGGACAATGATACGGGGTGGATTTCAGTAGCA
	TCCTCCCTGATTTCTGACTTGAACCAAAACTTTTTTATCACAGTCACTGCAAAGGATA
	AGGGAAACCCTCCACTTTCTTCCCAAGCAACTGTTCACATAACTGTCACTGAGGAAAA
	CTACCATACACCTGAATTCTCTCAAAGCCACATGAGTGCAACCATCCCTGAGAGCCAT
	AGCATTGGGTCCATTGTCAGAACTGTTTCTGCAAGAGATAGAGATGCAGCGATGAATG
	GCTTGATTAAGTACAGCATTTCTTCAGGAAATGAAGAAGGCATTTTTGCAATCAATTC
	TTCTACAGGTATATTAACACTAGCCAAAGCTCTTGATTATGAGCTATGCCAGAAACAC
	GAAATGACGATTAGTGCTATAGATGGAGGATGGGTTGCAAGAACTGGTTACTGCAGTG
	TGACCGTAAATGTGATTGATGTGAATGATAATTCTCCAGTATTCCTCTCTGATGACTA
	TTTCCCTACTGTTTTGGAAAATGCCCCAAGTGGAACAACAGTTATCCACCTAAATGCA
	ACAGATGCTGACTCTGGAACAAATGCTGTGATTGCGTATACTGTACAGTCATCTGACA
	GTGACCTCTTTGTCATTGACCCTAACACAGGAGTCATAACCACTCAAGGCTTCTTGGA
	TTTTGAAACCAAGCAGAGCTACCATCTTACTGTGAAAGCCTTCAATGTCCCCGATGAG
	GAAAGGTGTAGCTTTGCCACTGTTAATATACAATTAAAAGGGACAAATGAATATGTGC
	CCCGTTTTGTTTCCAAACTTTACTATTTTGAAATCTCAGAAGCAGCTCCTAAAGGTAC
	TATTGTTGGAGAAGTGTTTGCTAGCGACCGTGATTTGGGCACTGATGGGGAGGTACAC
	TATTTGATTTTTGGTAATAGTCGAAAGAAGGGTTTCCAGATCAATAAGAAGACTGGAC
	AGATTTATGTTTCTGGAATTCTTGATCGAAAAAAAGAAGAAAGGGTGTCTTTGAAGGT
	ATTGGCCAAGAACTTTGGCAGCATTAGAGGTGCAGATATAGATGAGGTCACTGTAAAT
	GTCACCGTGCTTGATGCAAATGACCCACCCATTTTTACTCTAAACATCTACAGTGTGC
	AGATCAGTGAAGGGGTCCCAATAGGAACTCATGTGACCTTTGTCAGTGCCTTTGACTC
	AGACTCCATCCCCAGCTGGAGCAGGTTTTCTTACTTCATCGGATCAGGGAATGAAAAT
	GGTGCCTTTTCTATTAATCCGCAGACAGGACAGATCACCGTTACTGCAGAATTAGATC
	GAGAAACCCTTCCCATCTATAATCTCTCAGTTTTGGCTGTTGATTCAGGGACCCCCTC
	AGCTACAGGTAGTGCCTCTTTATTAGTCACCCTGGAAGATATAAATGATAACGGGCCC
	ATGCTGACTGTCAGTGAAGGAGAAGTCATGGAAAACAAACGGCCAGGCACTTTGGTGA
	TGACCCTTCAGTCCACTGACCCTGATCTCCCTCCAAATCAAGGTCCCTTTACTTATTA
	CTTGCTGAGCACAGGTCCTGCCACCAGTTATTTCAGTCTGAGCACTGCTGGAGTTCTG
	AGCACAACCAGAGAGATTGACAGAGAGCAGATTGCAGACTTCTATCTGTCTGTGGTTA
	CCAAGGATTCTGGTGTTCCTCAAATGTCTTCCACAGGAACTGTGCATATCACAGTTAT
	AGACCAAAATGACAATCCTTCACAGTCTCGGACGGTGGAGATATTTGTTAATTATTAT
	GGTAACTTGTTTCCCGGTGGGATTTTAGGCTCTGTGAAGCCACAGGATCCAGATGTGT
	TAGACAGCTTCCACTGCTCCCTTACTTCAGGAGTTACCAGCCTCTTCAGTATTCCAGG
	GGGTACTTGTGATCTGAATTCCCAGCCAAGGTCCACAGATGGCACGTTTGATCTGACT
	GTCCTTAGCAATGATGGAGTTCACAGCACAGTCACGAGCAACATCCGAGTTTTCTTTG
	CTGGATTTTCCAATGCCACAGTGGATAACAGCATCTTACTTCGTCTCGGCGTACCAAC
	AGTAAAGGACTTCTTGACCAACCACTATCTTCATTTTTTACGCATTGCCAGCTCACAG
	CTGACAGGCTTAGGGACTGCTGTGCAACTGTACAGTGCATATGAAGAGAACAATAGAA
	CGTTTCTTTTGGCAGCTGTGAAGCGAAATCATAATCAGTATGTGAATCCCAGTGGCGT
	AGCCACCTTCTTTGAAAGCATCAAAGAGATCCTTCTCCGGCAGAGTGGAGTAAAGGTG
	GAATCTGTGGATCATGACTCCTGTGTGCATGGCCCATGTCAGAATGGAGGGAGCTGTC
	TACGAAGATTGGCTGTGAGCTCCGTATTAAAAAGCCGTGAGAGTCTTCCAGTCATCAT
	CGTGGCAAATGAACCTCTGCAGCCTTTCTTATGCAAGTGTCTGCCAGGATATGCGGGT
	AGCTGGTGTGAAATAGATATAGATGAATGTCTTCCATCACCTTGCCACAGTGGTGGAA
	CCTGTCACAATTTAGTGGGAGGATTTTCATGCAGCTGCCCAGATGGCTTCACTGGTAG
	GGCGTGTGAGAGAGATATCAATGAGTGCCTGCAGAGTCCTTGCAAGAATGGTGCCATC
	TGCCAGAATTTTCCAGGAAGCTTCAACTGTGTTTGCAAAACTGGATACACAGCTATGA
	CAACGTTTGTACTTTTCTCACTAAGACTTGGAAAATGTGTGAATCTTCAGTCAATTAC
	TGTGAATGCAACCCCTGCTTTAATGGTGGTTCCTGCCAAAGTGGTGTGGATTCTTATT
	ATTGTCATTGTCCATTTGGTGTCTTTGGAACACTGCGACTTGAACAGTTATGGATTTG
	AGGAGTTATCATACATGGAATTTCCAAGCTTGGACCCCAATAACAACTATATTTATGT
	CAAATTTGCCACGATTAAAAGTCATGCCTTATTGCTTTACAACTATGACAACCAGACA
	GGCGACCGGGCTGAGTTTTTGGCCCTTGAAATTGCCGAAGAAAGACTAAGATTCTCTT
	ATAATTTAGGCAGTGGTACATATAAGCTCACCACCATGAAGAAGGTGTCAGATGGACA
	TTTTCACACTGTGATTGCCAGGAGAGCAGGAATGGCAGCCTCCTTAACTGTGGACTCC
	TGTTCTGAGAACCAAGAGCCAGGATATTGTACTGTCAGTAATGTGGCAGTTTCAGATG
	ACTGGACTCTTGATGTTCAGCCAAATAGAGTTACAGTTGGAGGTATCAGATCTCTAGA
	ACCAATCCTTCAGAGAAGAGGACACGTGGAAAGCCATGATTTTGTTGGGTGTATAATG
	GAGTTTGCAGTCAATGGAAGGCCTCTGGAACCCAGCCAAGCTTTGGCAGCACAAGGCA
	TCCTAGATCAGTATGGCGATTTTATTTCTTACTGTTTTAAAGAAAAAAAATGCAAAAA
	AGTATGCTTCACTGTTACTCCTGACACTGCCTTATCATTAGAAGGCAAAGGGCGCTTG
	GACTACCACATGAGTCAGAATGAGAAGCGGGAATATTTGTTAAGGCAAAGCTTACGAG
	GTGCCATGTTGGAGCCTTTTGGTGTGAACAGTCTGGAAGTAAAATTTAGGACCAGAAG
	CGAGAATGGCGTTTTAATCCATATCCAAGAAAGCAGCAATTACACTACTGTGAAGGGA
	ATGTGTGAATCTTCAGTCAATTACTGTGAATGCAACCCCTGCTTTAATGGTGGTTCCT
	GCCAAAGTGGTGTGGATTCTTATTATTGTCATTGTCCATTTGGTGTCTTTGGAAAACA
	CTGCGAGTTGAACAGTTATGGATTTGAGGAGTTATCATACATGGAATTTCCAAGCTTG
	GACCCCAATAACAACTATATTTATGTCAAATTTGCCACGATTAAAAGTCATGCCTTAT
	TGCTTTACAACTATGACAACCAGACAGGCGACCGGGCTGAGTTTTTGGCCCTTGAAAT
	TGCCGAAGAAAGACTAAGATTCTCTTATAATTTAGGCAGTGGTACATATAAGCTCACC
	ACCATGAAGAAGGTGTCAGATGGACATTTTCACACTGTGATTGCCAGGAGAGCAGGAA
	TGACTCTTGATGTTCAGCCAAATAGAGTTACAGTTGGAGGTATCAGATCTCTAGAACC
	AATCCTTCAGAGAAGAGGACACGTGGAAAGCCATGATTTTGTTGGGTGTATAATGGAG
	TTTGCAGTCAATGGAAGGCCTCTGGAACCCAGCCAAGCTTTGGCAGCACAAGGCATCC
	TACATCAGTATGGCGATTTTATTTCTTACTGTTTTAAAGAAAAAAAATGCAAAAAGTA
	TGCTTCACTTGGCCTCCATCTCGGGAAGCATAGCTTGGCCTCCATCTCAAAAACAGAT
	CCCTCAGTGAAGATTGGCTGCCGTGGCCCGAACATTTGTGCCAGCAACCCCTGCTGGG
	GTGATTTGCTGTGCATTAATCAGTGGTATGCCTACAGGTGTGTCCCTCCTGGGGACTG
	TGCCTCCCACCCGTGCCAGAATGGTGGCAGCTGTGAGCCAGGCCTGCACTCCGGCTTC
	ACCTGTAGCTGCCCAGACTCGCACACGGGAAGGACCTGTGAGATGGTGGTGGCCTGTC
	TTGGCGTCCTCTGTCCTCAGGGGAAGGTGTGCAAAGCTGGAAGTCCTGCGGGGCATGT
	CTGTGTTCTGAGTCAGGGCCCTGAAGAGATCTCTCTGCCTTTGTGGGCTGTGCCTGCC
	ATCGTGGGCAGCTGCGCAACCGTCTTGGCCCTCCTGGTCCTTAGCCTGATCCTGTGTA
	ACCAGTGCAGGGGGAAGAAGCCCAAAAATCCCAAAGAGGAGAAGAAACCGAAGGAGAA
	GAAGAAAAAGGGAAGTGAGAACGTTGCTTTTGATGACCCTGACAATATCCCTCCCTAT
	GGGGATGACATGACTGTGAGGAAGCAGCCTGAAGGGAACCCAAAACCAGATATCATTG
	AAAGGGAAAACCCCTACCTTATCTATGATGAAACTGATATTCCTCACAACTCAGAAAC
	CATCCCCAGCGCCCCTTTGGCATCTCCAGAGCAGGAGATAGAGCACTATGACATTGAC
	AACGCCAGCAGCATCGCCCCTTCGGATGCAGACATCATTCAACACTACAAGCAGTTCC
	GCAGCCACACACCAAAATTTTCAATCCAGAGGCACAGTCCCCTAGGCTTTGCAAGGCA
	ATCCCCCATGCCCTTAGGAGCAAGCAGTTTGACTTACCAGCCTTCATATGGTCAAGGT
	TTGAGAACCAGCTCCCTAAGCCACTCAGCATGCCCAACTCCCAACCCTCTGTCTCGAC
	ACAGTCCAGCCCCTTTCTCCAAATCTTCTACGTTCTATAGAAACAGCCCAGCAAGGGA
	ATTGCATCTTCCTATAACGGATCGTAATACTTTGGAAATGCATGGTGACACCTGCCAA
	CCTGGCATTTTCAACTATGCCACAAGGCTGGGAAGGAGAAGCAAGAGTCCTCAGGCCA
	TGGCATCACATGGTTCTAGACCAGGGAGTCGCCTAAAGCAGCCGATTGGGCAGATTCC
	ACTGGAATCTTCTCCTCCAGTCGGACTTTCTATTGAAGAAGTGGAGAGGCTCAACACA
	CCTCGCCCTAGAAACCCAAGTATCTGCAGTGCAGACCATGGGAGGTCTTCTTCAGAGG
	AGGACTGCAGAAGGCCACTGTCTAGAACAAGGAATCCAGCGGATGGCATTCCAGCTCC
	AGAATCCTCTTCTGATAGTGACTCCCATGAATCTTTCACTTGCTCAGAAATGGAATAT
	GACAGGGAGAAGCCAATGGTATATACTTCCAGAATGCCCAAATTATCTCAAGTCAATG
	AATCTGATGCAGATGATGAACATAATTATGGAGCCAGACTGAAGCCTCGAAGGTACCA
	CGGTCGCAGGGCCGAGGGAGGACCTGTGGGCACCCAGGCAGCAGCACCAGGCACTGCT
	GACAACACACTGCCCATGAAGCTAGGGCAGCAAGCAGGGACTTTCAACTGGGACAACC
	TTTTGAACTGGGGCCCTGGCTTTGGCCATTATGTAGATGTTTTTAAAGATTTGGCATC
	TCTTCCAGAAAAAGCAGCAGCAAATGAAGAAGGCAAAGCTGGGACAACTAAACCAGTC
	CCCAAAGATGGGGAAGCAGAACAGTATGTGTGAAGTTTATGTACTGGCACTATAAAAT
	ATAAAAACAAGAAATAATACTCAAACCATTGTAAAGTTGCTGACTAGGTTGGGTCACA
	TTTGAAAAACAGGCCAGTATGGACTAGTGGTGGAGGGAJAACTTTAAAAATAATAACC
	ACAATGCTGCTGAAACAGACTCACAACAACTCTTAATTTAAACATGTGTGGTTGAATT
	C
	ORF Start: ATG at 518	ORF Stop: TGA at 15401
	SEQ ID NO: 64	4961 aa	MW at 543673.9 kD
NOV17a,	MDLAPDRATGRPWLPLHTLSVSQLLRVFWLLSLLPGQAWVHGAEPRQVFQVLEEQPPG
CG92813-01	TLVGTIQTRPGFTYRLSESHALFAINSSTGALYTTSTIDRESLPSDVINLVVLSSAPT
Protein Sequence	YPTEVRVLVRDLNDNAPVFPDPSIVVTFKEDSSSGRQVILDTATDSDIGSNGVDXRSY
	RIIRGNEAGRFRLDINLNPSGEGAFLHLVSKGGLDREVTPQYQLLVEVEDKGEPKRRG
	YLQVNVTVQDINDNPPVFGSSHYQAGVPEDAVVGSSVLQVAAADADEGTNADIRYRLQ
	DEGTPFQMDPETGLITVREPLDFEARRQYSLTVQANDRGVPSLTGRAEALIQLLDVND
	NDPVVKFRYFPATSRYASVDENAQVGTVVALLTVTDADSPAANGNISVQILGGNEQRH
	FEVQSSKVPNLSLIKVASALDRERIPSYNLTVSVSDNYGAPPGAAVQARSSVASLVIF
	VNDINDHPPVFSQQVYRVNLSEEAPPGSYVSGISATDGDSGLNANLRYSIVSGNGLGW
	FHISEHSGLVTTGSSGGLDRELASQIVLNISARDQGVHPKVSYAQLVVTLLDVNDEKP
	VFSQPEGYDVSVVENAPTGTELLMLRATDGDLGDNGTVRFSLQEAETDRRSFRLDPVS
	GRLSTISSLDREEQAFYSLLVLATDLGSPPQSSMARINVSLLDINDNSPVFYPVQYFA
	HIKENEPGGSYITTVSATDPDLGTNGTVKYSISAGDRSRFQVNAQSGVISTRMALDRE
	EKTAYQLQIVATDGGNLQSPNQAIVTITVLDTQDNPPVFSQVAYSFVVFENVALGYHV
	GSVSASTMDLNSNISYLITTGDQKGMFAINQVTGQLTTANVIDREEQSFYQLKVVASG
	GTVTGDTMVNITVKDLNDNSPHFLQAIESVNVVENWQAGHSIFQAKAVDPDEGVNGMV
	LYSLKQNPKNLFAINEKNGTISLLGPLDVHAGSYQIEILASDMGVPQLSSSVILTVYV
	HDVNDNSPVFDQLSYEVTLSESEPVNSRFFKVQASDKDSGANDGQLYIKSELDRELQD
	RYVLMVVASDRAVEPLSATVNVTVILEDVNDNRPLFNSTNYTFYFEEEQRAGSFVGKV
	SAVDKDFGPNGEVRYSFEMVQPDFELHAISGEITNTHQFDRESLMRRRGTAVFSFTVI
	ATDQGIPQPLKDQATVHVYMKDINDNAPKFLKDFYQATISESAANLTQVLRVSASDVD
	EGNNGLIHYSIIKGNEERQFAIDSTSGQVTLIGKLDYEATPAYSLVIQAVDSGTIPLN
	STCTLNIDILDENDNTPSFLKSTLFVDVLENMRIGELVSSVTATDSDSGDNVDLYYSI
	TGTNNHGTFSISPNTGSIFLAKKLDFETQSLYKLNITAKDQGRPPRSSTMSVVIHVRD
	FNDNPPSFPPGDIFKSIVENIPIGTSVISVTAHDPDADINGQLSYTIIQQMPRGNHFT
	IDEVKGTIYTNAEIDREFANLFELTVKANDQAVPIETRRYALKNVTILVTDLNDNVPM
	FISQNALAADPSAVIGSVLTTIMAADPDEGANGEIEYEIINGDTDTFIVDRYSGDLRV
	ASALVPSQLIYNLIVSATDLGPERRKSTTELTIILQGLDGPVFTQPKYITILKEGEPI
	GTNVISIEAASPRGSEAPVEYYIVSVRCEEKTVGRLFTIGRHTGIIQTAAILDREQGA
	CLYLVDVYAIEKSTAFPRTQRAEVETTLQDINDNPPVFPTDMLDLTVEENIGDGSKIM
	QLTAMDADEVQMLSSHTLSLVGSLVAAILATDDDSGVNGEITYIVNEDDEDGIFFLNP
	ITGVFNLTRLLDYEVQQYYILTVRAEDGGGQFTTIRVYFNILDVNDNPPIFSLNSYST
	SLMENLPVGSTVLVFNVTDADMMKAEIKMFFETSENKDTTYQNLWDTFKAVCRGKFIA
	LNAHKRKQERSKIDTLTSQLKELEKQEQTHSKASRRQEITKIRAELKDIETQKTLQKI
	NESRSWFFERINKIDRPLARLIKKKTEKNQIDAIKNDKGDITIDPTEIQTTIREYCKH
	LYANKLENLEEMDKFLDTYTLPRLNQEEVESLNRPITDSETVAIINSLPTKKSPGPDG
	FTAEFYQMITTPVFAQALYKVEINENTLTGTDIIQVFAADGDEGTNGQVRYGIVNGNT
	NQEFRIDSVTGAITVAKPLDREKTPTYHLTVQATDRGSTPRTDTSTVSIVLLDINDFV
	PVFELSPYSVNVPENLGTLPRTILQTASPCVRFASASKAYFTTIPEDAPTGTDVLLVN
	ASDADASKNAVISYRIIGGNSQFTINPSTGQIITSALLDRETKDNYTLVVVCSDAGSP
	EPLSSSTSVLVTVTDVHDNPPRFQHHPYVTHIPSPTLPGSFVFAVTVTDADIGPNSEL
	HYSLSGRNSEKFHIDPLRGAIMAAGPLNGASEVTFSVHVKDGGSFPKTDSTTVTVRFV
	NKADFPKVRAKEQTFMFPENQPVSSLVTTITGSSLRGEPMSYYIASGNLGNTFQIDQL
	TGQVSISQPLDFEKIQKYVVWIEARDGGFPPFSSYEKLDITVLDVNDNAPIFKEDPFI
	SEILENLSPRKILTVSAMDKDSGPNGQLDYEIVNGNMENSFSINHATGEIRSVRPLDR
	EKVSHYVLTIKSSDKGSPSQSTSVKVMINILDENDNAPRFSQIFSAHVPENSPLGYTV
	TRVTTSDEDIGINAISRYSIMDASLPFTINPSTGDIVISRPLNREDTDRYRIRVSAHD
	SGWTVSTDVTIFVTDINDNAPRFSRTSYYLDCPELTEIGSKVTQVFATDPDEGSNGQV
	FYFIKSQSEYFRINATTGEIFNKQILKYQNVTGFSNVNINRHSFIVTSSDRGKPSLIS
	ETTVTINIVDSNDNAPQFLKSKYFTPVTKNVKVGTKLIRVTAIDDKDFGLNSEVEYFI
	SNDNHLGKFKLDNDTGWISVASSLISDLNQNFFITVTAKDKGNPPLSSQATVHITVTE
	ENYHTPEFSQSHMSATIPESHSIGSIVRTVSARDRDAAMNGLIKYSISSGNEEGIFAI
	NSSTGILTLAKALDYELCQKHEMTISAIDGGWVARTGYCSVTVNVIDVNDNSPVFLSD
	DYFPTVLENAPSGTTVIHLNATDADSGTNAVIAYTVQSSDSDLFVIDPNTGVITTQGF
	LDFETKQSYHLTVKAFNVPDEERCSFATVNIQLKGTNEYVPRFVSKLYYFEISEAAPK
	GTIVGEVFASDRDLGTDGEVHYLIFGNSRKKGFQINKKTGQIYVSGILDRKKEERVSL
	KVLAKNFGSIRGADIDEVTVNVTVLDANDPPIFTLNIYSVQISECVPIGTHVTFVSAF
	DSDSIPSWSRFSYFIGSGNENGAFSINPQTGQITVTAELDRETLPIYNLSVLAVDSGT
	PSATGSASLLVTLEDINDNGPMLTVSEGEVMENKRPGTLVMTLQSTDPDLPPNQGPFT
	YYLLSTGPATSYFSLSTAGVLSTTREIDREQIADFYLSVVTKDSGVPQMSSTGTVHIT
	VIDQNDNPSQSRTVEIFVNYYGNLFPGGILGSVKPQDPDVLDSFHCSLTSGVTSLFSI
	PGGTCDLNSQPRSTDGTFDLTVLSNDGVHSTVTSNIRVFFAGFSNATVDNSILLRLGV
	PTVKDFLTNHYLHFLRIASSQLTGLGTAVQLYSAYEENNRTFLLAAVKRNHNQYVNPS
	GVATFFESIKEILLRQSGVKVESVDHDSCVHGPCQNGGSCLRRLAVSSVLKSRESLPV
	IIVANEPLQPFLCKCLPGYAGSWCEIDIDECLPSPCHSGGTCHNLVGGFSCSCPDGFT
	GRACERDINECLQSPCKNGAICQNFPGSFNCVCKTGYTGMTTFVLFSLRLGKCVNLQS
	ITVNATPALMVVPAKVVWILIIVIVHLVSLEHCELNSYGFEELSYMEFPSLDPNNNYI
	YVKFATIKSHALLLYNYDNQTGDRAEFLALEIAEERLRFSYNLGSGTYKLTTMKKVSD
	GHFHTVIARRAGMAASLTVDSCSENQEPGYCTVSNVAVSDDWTLDVQPNRVTVGGIRS
	LEPILQRRGHVESHDFVGCIMEFAVNGRPLEPSQALAAQGILDQYGDFISYCFKEKKC
	KKVCFTVTPDTALSLEGKGRLDYHMSQNEKREYLLRQSLRGANLEPFGVNSLEVKFRT
	RSENGVLIHIQESSNYTTVKGMCESSVNYCECNPCFNGGSCQSGVDSYYCHCPFGVFG
	KHCELNSYGFEELSYMEFPSLDPNNNYIYVKFATIKSHALLLYNYDNQTGDRAEFLAL
	EIAEERLRFSYNLGSGTYKLTTMKKVSDGHFHTVIARRAGMTLDVQPNRVTVGGIRSL
	EPILQRRGHVESHDFVGCIMEFAVNGRPLEPSQALAAQGILDQYGDFISYCFKEKKCK
	KYASLGLHLGKHSLASISKTDPSVKIGCRGPNICASNPCWGDLLCINQWYAYRCVPPG
	DCASHPCQNGGSCEPGLHSGFTCSCPDSHTGRTCEMVVACLGVLCPQGKVCKAGSPAG
	IVCVLSQGPEEISLPLWAVPAIVGSCATVLALLVLSLILCNQCRGKKAKNPKEEKKPK
	EKKKKGSENVAFDDPDNIPPYGDDMTVRKQPEGNPKPDIIERENPYLIYDETDIPHNS
	ETIPSAPLASPEQEIEHYDIDNASSIAPSDADIIQHYKQFRSHTPKFSIQRHSPLGFA
	RQSPMPLGASSLTYQPSYGQGLRTSSLSHSACPTPNPLSRHSPAPFSKSSTFYRNSPA
	RELHLPIRDGNTLEMHGDTCQPGIFNYATRLGRRSKSPQANASHGSRPGSRLKQPIGQ
	IPLESSPPVGLSIEEVERLNTPRPRNPSICSADHGRSSSEEDCRRPLSRTRNPADGIP
	APESSSDSDSHESFTCSEMEYDREKPMVYTSRMPKLSQVNESDADDEDNYGARLKPRR
	YHGRRAEGGPVGTQAAAPGTADNTLPMKLGQQAGTFNWDNLLNWGPGFGHYVDVFKDL
	ASLPEKAAANEEGKAGTTKPVPKDGEAEQYV

[0358] Further analysis of the NOV17a protein yielded the following properties shown in Table 17B.

TABLE 17B
Protein Sequence Properties NOV17a
PSort     0.8000 probability located in nucleus; 0.6000 probability located in plasma
analysis: membrane; 0.4000 probability located in Golgi body; 0.3000 probability located
          in endoplasmic reticulum (membrane)
SignalP   Cleavage site between residues 43 and 44
analysis:

[0359] 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 17C.

TABLE 17C
Geneseq Results for NOV17a
		NOV17a	Identities
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABG22977	Novel human diagnostic protein	119 . . . 4188	1159/4320 (26%)	0.0
	#22968 - Homo sapiens, 4591 aa.	134 . . . 4099	1853/4320 (42%)
	[WO200175067-A2,
	11-OCT-2001]
ABG22977	Novel human diagnostic protein	119 . . . 4188	1159/4320 (26%)	0.0
	#22968 - Homo sapiens, 4591 aa.	134 . . . 4099	1853/4320 (42%)
	[WO200175067-A2,
	11-OCT-2001]
AAM52106	Rat fat 3 protein SEQ ID NO 3 -	70 . . . 3771	1054/3877 (27%)	0.0
	Rattus norvegicus, 4555 aa.	192 . . . 3829	1742/3877 (44%)
	[JP2001258573-A, 25-SEP-2001]
AAU07054	Human Flamingo protein encoded	2627 . . . 4042	427/1490 (28%)	e−137
	by cDNA splice variant - Homo	162 . . . 1566	665/1490 (43%)
	sapiens, 2923 aa. [WO200161003-A1,
	23-AUG-2001]
AAU07053	Human Flamingo polypeptide -	2627 . . . 4042	427/1490 (28%)	e−137
	Homo sapiens, 2956 aa.	162 . . . 1566	665/1490 (43%)
	[WO200161003-A1,
	23-AUG-2001]

[0360] 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 17D.

TABLE 17D
Public BLASTP Results for NOV17a
		NOV17a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P33450	Cadherin-related tumor suppressor	49 . . . 1878	748/1932 (38%)	0.0
	precursor (Fat protein) - Drosophila	71 . . . 1951	1066/1932 (54%)
	melanogaster (Fruit fly), 5147 aa.
IJFFTM	cadherin-related tumor suppressor	49 . . . 1878	744/1932 (38%)	0.0
	precursor - fruit fly (Drosophila	71 . . . 1951	1065/1932 (54%)
	melanogaster), 5147 aa.
Q96JQ0	Protocadherin 16 precursor	5 . . . 1877	621/1950 (31%)	0.0
	(Cadherin 19)	12 . . . 1883	925/1950 (46%)
	(Cadherin fibroblast 1) - Homo sapiens
	(Human), 3298 aa.
Q99PF4	Cadherin 23 precursor (Otocadherin) -	53 . . . 1877	606/1927 (31%)	0.0
	Mus musculus (Mouse),	588 . . . 2430	896/1927 (46%)
	3354 aa.
P58365	Cadherin 23 precursor (Otocadherin) -	53 . . . 1877	613/1928 (31%)	0.0
	Rattus norvegicus (Rat), 3317 aa.	586 . . . 2428	897/1928 (45%)

[0361] PFam analysis indicates that the NOV17a protein contains the domains shown in Table 17E.

TABLE 17E
Domain Analysis of NOV17a
		Identities/
	NOV17a	Similarities for
	Match	the Matched	Expect
Pfam Domain	Region	Region	Value
cadherin: domain 1 of 30	47 . . . 126	19/107	(18%)	0.012
		59/107	(55%)
cadherin: domain 2 of 30	140 . . . 241	36/113	(32%)	4.6e−15
		76/113	(67%)
cadherin: domain 3 of 30	255 . . . 344	43/107	(40%)	1.3e−27
		75/107	(70%)
cadherin: domain 4 of 30	363 . . . 466	43/113	(38%)	2.9e−23
		79/113	(70%)
cadherin: domain 5 of 30	480 . . . 573	36/109	(33%)	3.5e−24
		75/109	(69%)
cadherin: domain 6 of 30	588 . . . 680	46/108	(43%)	5.3e−27
		76/108	(70%)
cadherin: domain 7 of 30	694 . . . 784	43/107	(40%)	7.2e−27
		67/107	(63%)
cadherin: domain 8 of 30	798 . . . 884	34/107	(32%)	4.2e−18
		66/107	(62%)
cadherin: domain 9 of 30	898 . . . 987	31/107	(29%)	1.3e−18
		66/107	(62%)
cadherin: domain 10 of 30	1001 . . . 1071	26/107	(24%)	1.6e−08
		59/107	(55%)
cadherin: domain 11 of 30	1085 . . . 1181	34/111	(31%)	1.6e−14
		72/111	(65%)
Isochorismatase:	1038 . . . 1206	27/213	(13%)	8.8
domain 1 of 1		112/213	(53%)
cadherin: domain 12 of 30	1195 . . . 1286	38/107	(36%)	3.2e−27
		76/107	(71%)
cadherin: domain 13 of 30	1300 . . . 1391	41/107	(38%)	7.3e−27
		70/107	(65%)
cadherin: domain 14 of 30	1405 . . . 1500	38/108	(35%)	5.3e−19
		73/108	(68%)
cadherin: domain 15 of 30	1506 . . . 1602	29/114	(25%)	6.8e−12
		70/114	(61%)
cadherin: domain 16 of 30	1614 . . . 1711	28/112	(25%)	0.014
		63/112	(56%)
S-AdoMet- syntD2:	1789 . . . 1803	8/15	(53%)	3.8
domain 1 of 1		12/15	(80%)
cadherin: domain 17 of 30	1754 . . . 1840	31/107	(29%)	2.2e−14
		64/107	(60%)
cadherin: domain 18 of 30	2107 . . . 2198	45/107	(42%)	6.4e−31
		76/107	(71%)
cadherin: domain 19 of 30	2244 . . . 2334	44/107	(41%)	2.2e−28
		72/107	(67%)
cadherin: domain 20 of 30	2348 . . . 2436	34/107	(32%)	1.8e−12
		66/107	(62%)
cadherin: domain 21 of 30	2449 . . . 2537	36/107	(34%)	1.2e−11
		65/107	(61%)
cadherin: domain 22 of 30	2551 . . . 2641	37/107	(35%)	9.7e−26
		72/107	(67%)
cadherin: domain 23 of 30	2654 . . . 2740	38/107	(36%)	3.2e−17
		63/107	(59%)
cadherin: domain 24 of 30	2754 . . . 2851	31/116	(27%)	5.3e−16
		74/116	(64%)
cadherin: domain 25 of 30	2865 . . . 2957	40/107	(37%)	4.3e−16
		68/107	(64%)
cadherin: domain 26 of 30	2971 . . . 3062	37/107	(35%)	3.2e−26
		74/107	(69%)
cadherin: domain 27 of 30	3076 . . . 3164	36/108	(33%)	4.2e−21
		67/108	(62%)
cadherin: domain 28 of 30	3180 . . . 3273	33/107	(31%)	1.8e−16
		71/107	(66%)
cadherin: domain 29 of 30	3286 . . . 3378	38/107	(36%)	2e−27
		78/107	(73%)
PEP-utilizers:	3326 . . . 3392	17/107	(16%)	5.2
domain 1 of 1		43/107	(40%)
cadherin: domain 30 of 30	3390 . . . 3482	37/109	(34%)	1e−21
		75/109	(69%)
EGF: domain 1 of 5	3683 . . . 3736	14/64	(22%)	7.1
		33/64	(52%)
EGF: domain 2 of 5	3743 . . . 3774	18/47	(38%)	2.1e−08
		25/47	(53%)
metalthio: domain 1 of 1	3745 . . . 3805	16/70	(23%)	7.8
		29/70	(41%)
EGF: domain 3 of 5	3781 . . . 3812	15/47	(32%)	8.9e−05
		25/47	(53%)
EB: domain 1 of 1	3765 . . . 3823	16/70	(23%)	3.7
		41/70	(59%)
laminin_G: domain 1 of 4	3890 . . . 4033	48/163	(29%)	5.8e−19
		99/163	(61%)
laminin_G: domain 2 of 4	4116 . . . 4125	5/10	(50%)	5.6
		10/10	(100%)
EGF: domain 4 of 5	4148 . . . 4179	16/47	(34%)	0.013
		24/47	(51%)
laminin_EGF:	4148 . . . 4195	15/64	(23%)	2
domain 1 of 1		33/64	(52%)
laminin_G: domain 3 of 4	4208 . . . 4272	26/77	(34%)	4.5e−09
		48/77	(62%)
laminin_G: domain 4 of 4	4286 . . . 4322	14/37	(38%)	0.0066
		27/37	(73%)
EGF: domain 5 of 5	4410 . . . 4442	16/47	(34%)	3e−06
		26/47	(55%)

Example 18

[0362] 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:65	2118 bp
NOV18a,	GGAGTGAACTAACACAAAGTTACGAATTCTTATTGGTTTACAAAAACAATGTTGATTA
CG92844-DNA	GTGATTGGCTATATACATTGTTAAGGTATAGGGTGTGGCTCGCCGGTGCCCTCGACCT
Sequence	GCCCGCTGGGTCCTGTGCCTTTGAAGAGAGCACTTGCGGCTTTGACTCCGTGTTGGCC
	TCTCTCCCGTGGATTTTAAATGAGGAAGCCCATTACATTTATGTGGATACCTCCTTTG
	GCAAGCAGGGGGAGAAAGCTGTGCTGCTAAGTCCTGACTTACAGGCTGAGGAATGGAG
	CTGCCTCCGTTTCGTCTACCAGATAACCACATCTTCGGAGTCTCTGTCAGATCCCAGC
	CAGCTGAACCTCTACATGAGATTTGAAGATGAAAGCTTTGATCGCTTGCTTTGGTCAG
	CTAAGGAACCTTCAGACAGCTGGCTCATAGCCAGCTTGGATTTGCAAAACAGTTCCAA
	GAAATTCAAGATTTTAATAGAAGGTGTACTAGGACAGGGAAACACAGCCAGCATCGCA
	CTATTTGAAATCAAGATGACAACCGGCTACTGTATTGAATGTGACTTTGAAGAAAATC
	ATCTCTGTGGCTTTGTGAACCGCTGGAATCCCAATGTGAACTGGTTTGTTGGAGGAGG
	AAGTATTCGGAATGTCCACTCCATTCTCCCACAGGATCACACCTTCAAGAGTGAACTG
	GGTCACTACATGTACGTGGACTCAGTTTATGTGAAGCACTTCCAGGAGGTGGCACAGC
	TCATCTCCCCGTTGACCACGGCCCCCATGGCTGGCTGCCTGTCATTTTATTACCAGAT
	CCAGCAGGGGAATGACAATGTCTTTTCCCTTTACACTCGGGATGTGCCTGCCCTTTAC
	GAGGAAATCTGGAAAGCAGACAGGCCAGGGAATGCTGCCTGGAACCTTGCGGAGGTCG
	AGTTCAGTGCTCATTTTCCTCTGCAGGTTATTTTTGAAGTTGCTTTCAATGGTCCCAA
	GGGAGGTTATGTTGCCCTGGATGATATTTCATTCTCTCCTGTTCACTGCCAGAATCAG
	ACAGGTCTTCTGTTCAGTGCCGTGGAAGCCAGCTGCAATTTTGAGCAAGATCTCTGCA
	ACTTTTACCAAGATAAAGAAGGTCCAGGTTGGACCCGAGTGAAAGTAAAACCAAACAT
	GTATCGGGCTGGAGACCACACTACAGGCTTAGGTTATTACCTCCTACCCAACACAAAG
	TTCACATCTCAGCCTGGCTACATTGGAAGGCTCTATGGGCCCTCCCTACCAGGAAACT
	TGCAGTATTGTCTGCGTTTTCATTATCCCATCTATGGATTTTTAAAAATGAGTGACAC
	CCTAGCAGTTTACATCTTTGAAGAGAACCATGTGGTTCAAGAGAAGATCTGGTCTGTG
	TTGGAGTCCCCAAGGGGTGTTTGGATGCAAGCTGAAATCACCTTTAAGAAGCCCATGC
	CTTTTCAGGTGGTTTTCATGAGCCTATGCAAAAGTTTCTGGGACTGTGCGCTTGTAGC
	CCTGGATGACATTACAATACAATTGGGAAGCTGCTCATCTTCAGAGAAACTTCCACCT
	CCACCTGGAGAGTGTACTTTCGAGCAAGATGAATGTACATTTACTCAGGAGAAAAGAA
	ACCGGAGCAGCTGGCACAGGAGGAGGGGAGAAACTCCCACTTCCTACACAGGACCAAA
	GGGAGATCACACTACTGGGGTAGGCTACTACATGTACATTGAGGCCTCCCATATGGTG
	TATGGACAAAAAGCACGCCTCTTGTCCAGGCCTCTGCGAGGAGTCTCTGGAAAACACT
	GCTTGACCTTTTTCTACCACATGTATGGAGGGGGCACTGGCCTGCTGAGTGTTTATCT
	GAAAAAGGAAGAAGACAGTGAAGAGTCCCTCTTATGGAGGAGAAGAGGTGAACAGAGC
	ATTTCCTGGCTACGAGCACTGATTGAATACAGCTGTGAGAGGCAACACCAGATAATTT
	TTGAAGCCATTCGAGGAGTATCAATAAGAAGTGATATTGCCATTGATGATGTTAAATT
	TCAGGCAGGACCCTGTCAATCATCAGGATATTCTGAGGACTTAAATGAAATTGAGTAT
	TAAGAAATGATCTGCATTGGATTTACTAGA
	ORF Start: ATG at 49	ORF Stop: TAA at 2089
	SEQ ID NO:66	680 aa	MW at 77231.5 kD
NOV 18a,	MLISDWLYTLLRYRVWLAGALDLPAGSCAFEESTCGFDSVLASLPWILNEEGHYIYVD
CG92844-01	TSFGKQGEKAVLLSPDLQAEEWSCLRLVYQITTSSESLSDPSQLNLYMRFEDESFDRL
Protein Sequence	LWSAKEPSDSWLIASLDLQNSSKKFKILIEGVLGQGNTASIALFEIKMTTGYCIECDF
	EENHLCGFVNRWNPNVNWFVGGGSIRNVHSILPQDHTFKSELGHYMYVDSVYVKHFQE
	VAQLISPLTTAPMAGCLSFYYQIQQGNDNVFSLYTRDVAGLYEEIWKADRPGNAAWNL
	AEVEFSAHFPLQVIFEVAFNGPKGGYVALDDISFSPVHCQNQTGLLFSAVEASCNFEQ
	DLCNFYQDKEGPGWTRVKVKPNMYRAGDHTTGLGYYLLANTKFTSQPGYIGRLYGPSL
	PGNLQYCLRFHYAIYGFLKMSDTLAVYIFEENHVVQEKIWSVLESPRGVWMQAEITFK
	KPMPFQVVFMSLCKSFWDCGLVALDDITIQLGSCSSSEKLPPPPGECTFEQDECTFTQ
	EKRNRSSWHRRRGETPTSYTGPKGDHTTGVGYYMYIEASHMVYGQKARLLSRPLRGVS
	GKHCLTFFYHMYGGGTGLLSVYLKKEEDSEESLLWRRRGEQSISWLRALIEYSCERQH
	QIIFEAIRGVSIRSDIAIDDVKFQAGPCQSSGYSEDLNEIEY
	SEQ ID NO: 67	2023 bp
NOV18b,	GGATCCTTTGAAGAGAGCACTTGCGGCTTTGACTCCGTGTTGGCCTCTCTGCCGTGGA
174308357 DNA	TTTTAAATGAGGAAGGCCATTACATTTATGTGGATACCTCCTTTGGCAAGCAGGGGGA
Sequence	GAAAGCTGTGCTGCTAAGTCCTGACTTACAGGCTGAGGAATGGAGCTGCCTCCGTTTG
	GTCTACCAGATAACCACATCTTCGGAGTCTCTGTCAGATCCCAGCCAGCTGAACCTCT
	ACATGAGATTTGAAGATGAAAGCTTTGATCGCTTGCTTTGGTCAGCTAAGGAACCTTC
	AGACAGCTGGCTCATAGCCAGCTTGGATTTGCAAAACAGTTCCAAGAAATTCAAGATT
	TTAATAGAAGGTGTACTAGGACAGGGAAACACAGCCAGCATCGCACTATTTCAAATCA
	AGATGACAACCGGCTACTGTATTGAATCTGACTTTGAAGAAAATCATCTCTGTGGCTT
	TGTGAACCGCTGGAATCCCAATGTGAACTGGTTTGTTGGAGGAGGAAGTATTCGGAAT
	GTCCACTCCATTCTCCCACAGGATCACACCTTCAAGAGTGAACTGGGCCACTACATGT
	ACGTGGACTCAGTTTATGTGAAGCACTTCCAGGAGGTGGCACAGCTCATCTCCCCGTT
	GACCACGGCCCCCATGGCTGGCTCCCCGTCATTTTATTACCAGATCCAGCACGGGAAT
	GACAATGTCTTTTCCCTTTACACTCGGGATGTGGCTGGCCTTTACGAGGAAATCTGGA
	AAGCAGACAGGCCAGGGAATGCTGCCTGGAACCTTGCGGAGGTCGAGTTCAATOCTCC
	TTACCCCATGGAGGTTATTTTTGAAGTTGCTTTCAATGGTCCCAAGGGAGGTTATGTT
	GCCCTGGATGATATTTCATTCTCTCCTGTTCACTGCCAGAATCAGACAGAACTTCTGT
	TCAGTGCCGTGGAAGCCAGCTGCAATTTTGAGCAAGATCTCTGCAACTTTTACCAAGA
	TAAAGAAGGTCCAGGTTGGACCCGAGTGAAAGTAAAACCAAACATGTATCGGGCTGGA
	GACCACACTACAGGCTTAGGGTATTACCTGCTAGCCAACACAAAGTTCACATCTCAGC
	CTGGCTACATTGGAAGGCTCTATGGGCCCTCCCTACCAGGAAACTTGCAGTATTGTCT
	GCGTTTTCATTATGCCATCTATGGATTTTTAAAAATGAGTGACACCCTAGCAGTTTAC
	ATCTTTGAAGAGAACCATGTGGTTCAAGAGAAGATCTGGTCTGTGTTGGAGTCCCCAA
	GGGGTGTTTGGATGCAAGCTGAAATCACCTTTAAGAAGCCCATGCCTACCAAGGTGGT
	TTTCATGAGCCTATGCAAAAGTTTCTGGGACTGTGGGCTTGTAGCCCTGGATGACATT
	ACAATACAATTGGGAAGCTGCTCATCTTCAGAGAAACTTCCACCTCCACCTGGAGAGT
	GTACTTTCGAGCAAGATGAATGTACATTTACTCAGGAGAAAAGAAACCGGAGCAGCTG
	GCACAGGAGGAGGGGAGAAACTCCCACTTCCTACACAGGACCAAAGGGAGATCACACT
	ACTGGGGTAGGCTACTACATCTACATTGAGGCCTCCCATATGGTGTATGGACAAAAAG
	CACGCCTCTTGTCCAGGCCTCTGCGAGGAGTCTCTGGAAAACACTGCTTGACCTTTTT
	CTACCACATGTATGGAGGGGGCACTGGCCTGCTGAGTGTTTATCTGAAAAAGGAAGAA
	GACAGTGAAGAGTCCCTCTTATGGAGGAGAAGAGGTGAACAGACCATTTCCTGGCTAC
	GAGCACTGATTGAATACAGCTGTGAGACGCAACACCAGATGATTTTTGAAGCCATTCG
	AGGAGTATCAATAAGAAGTGATATTGCCATTGATGATGTTAAATTTCAGGCAGGACCC
	TGTGGAGAAATGGAAGATACAACTCAACAATCATCAGGATATTCTGAGGACTTAAATG
	AAATTGAGTATCTCGAGGAGTCAAAGCCGCAAGTGCTCTCTTCAAAGGTCC
	ORF Start: at 1	ORF Stop: at 2023
	SEQ ID NO:68	674 aa	MW at 76492.5 kD
NOV18b,	GSFEESTCGFDSVLASLPWILNEEGHYIYVDTSFGKQGEKAVLLSPDLQAEEWSCLRL
174308357 Protein	VYQITTSSESLSDPSQLNLYMRFEDESFDRLLWSAKEPSDSWLIASLDLQNSSKKFKI
Sequence	LIEGVLGQGNTASIALFEIKMTTGYCIECDFEENHLCGFVNRWNPNVNWFVGGGSIRN
	VHSILPQDHTFKSELGHYMYVDSVYVKHFQEVAQLISPLTTAPMAGCPSFYYQIQQGN
	DNVFSLYTRDVAGLYEEIWKADRPGNAAWNLAEVEFNAPYPMEVIFEVAFNGPKGGYV
	ALDDISFSPVHCQNQTELLFSAVEASCNFEQDLCNFYQDKEGPGWTRVKVKPNMYRAG
	DHTTGLCYYLLANTKFTSQPGYIGRLYGPSLPGNLQYCLRFHYAIYGFLKMSDTLAVY
	IFEENHVVQEKIWSVLESPRGVWMQAEITFKKPMPTKVVFMSLCKSFWDCGLVALDDI
	TIQLGSCSSSEKLPFPPGECTFEQDECTFTQEKRNRSSWHRRRGETPTSYTGPKGDHT
	TGVGYYMYIEASHMVYGQKARLLSRPLRGVSGKHCLTFFYHMYGGGTGLLSVYLKKEE
	DSEESLLWRRRGEQSISWLRALIEYSCERQHQMIFEAIRGVSIRSDIAIDDVKFQAGP
	CGEMEDTTQQSSGYSEDLNEIEYLEESKPQVLSSKV

[0363] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 18B.

TABLE 18B
Comparison of NOV18a against NOV18b.
	Protein	NOV18a Residues/	Identities/Similarities
	Sequence	Match Residues	for the Matched Region
	NOV18b	29 . . . 680	629/660 (95%)
		2 . . . 661	636/660 (96%)

[0364] Further analysis of the NOV18a protein yielded the following properties shown in Table 18C.

TABLE 18C
Protein Sequence Properties NOV18a
PSort     0.7480 probability located in microbody (peroxisome); 0.6736 probability
analysis: located in nucleus; 0.6415 probability located in mitochondrial matrix space;
          0.3377 probability located in mitochondrial inner membrane
SignalP   Cleavage site between residues 30 and 31
analysis:

[0365] 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 18D.

TABLE 18D
Geneseq Results for NOV18a
		NOV18a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB53298	Human polypeptide #38 - Homo	17 . . . 680	659/672 (98%)	0.0
	sapiens, 686 aa. [WO200181363-A1,	15 . . . 686	661/672 (98%)
	01-NOV-2001]
AAB01432	Human TANGO 239 (form 2) -	17 . . . 680	655/672 (97%)	0.0
	Homo sapiens, 686 aa.	15 . . . 686	660/672 (97%)
	[WO200039284-A1, 06-JUL-2000]
ABB53297	Human polypeptide #37 - Homo	52 . . . 680	624/637 (97%)	0.0
	sapiens, 640 aa. [WO200181363-A1,	4 . . . 640	626/637 (97%)
	01-NOV-2001]
AAB01426	Human TANGO 239 - Homo	17 . . . 506	482/490 (98%)	0.0
	sapiens, 549 aa. [WO200039284-A1,	15 . . . 504	487/490 (99%)
	06-JUL-2000]
AAB00036	Human TANGO 239 partial	26 . . . 500	456/475 (96%)	0.0
	sequence - Homo sapiens, 465 aa.	1 . . . 465	461/475 (97%)
	[WO200039284-A1, 06-JUL-2000]

[0366] 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 18E.

TABLE 18E
Public BLASTP Results for NOV18a
		NOV18a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organisum/Length	Residues	Portion	Value
Q91641	Thyroid hormone-induced protein B	1 . . . 680	438/689 (63%)	0.0
	precursor - Xenopus laevis (African	1 . . . 688	547/689 (78%)
	clawed frog), 688 aa.
Q96BM4	HYPOTHETICAL 26.4 KDA	457 . . . 680	222/232 (95%)	e−129
	PROTEIN - Homo sapiens ( Human),	1 . . . 232	223/232 (95%)
	232 aa.
CAD13324	BA373A9.2 (NOVEL PROTEIN	554 . . . 680	127/135 (94%)	4e−67
	(ORTHOLOG OF X. LAEVIS	1 . . . 135	127/135 (94%)
	THYROID HORMONE-INDUCED
	PROTEIN B)) - Homo sapiens
	(Human), 135 aa (fragment).
Q63191	Apical endosomal glycoprotein	272 . . . 670	108/412 (26%)	5e−29
	precursor - Rattus norvegicus (Rat),	587 . . . 975	182/412 (43%)
	1216 aa.
Q9GMT4	HYPOTHETICAL 51.2 KDA	511 . . . 666	66/172 (38%)	1e−20
	PROTEIN - Macaca fascicularis	240 . . . 411	87/172 (50%)
	(Crab eating macaque) (Cynomolgus
	monkey), 448 aa.

[0367] PFam analysis indicates that the NOV18a protein contains the domains shown in Table 18F.

TABLE 18F
Domain Analysis of NOV18a
		Identities/
	NOV18a	Similarities
	Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
MAM: domain 1 of 4	28 . . . 171	54/176 (31%)	1.3e−34
		123/176 (70%)
MAM: domain 2 of 4	172 . . . 331	49/175 (28%)	3.5e−35
		115/175 (66%)
TonB_boxC:	448 . . . 463	2/16 (12%)	5
domain 1 of 1		14/16 (88%)
MAM: domain 3 of 4	344 . . . 500	59/174 (34%)	7.3e−43
		120/174 (69%)
pili_assembly_C:	607 . . . 623	5/17 (29%)	6.8
domain 1 of 1		15/17 (88%)
MAM: domain 4 of 4	511 . . . 668	68/174 (39%)	6.8e−59
		129/174 (74%)

Example 19

[0368] 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:69          3815 bp
NOV19a,          CGGCCGCGATCCCCACCACACCACCAGCCCGGCCGCACGGGGCACTGAGCCGGGTGCT
CG93 088-01 DNA  GAGCACCGGAGGCCCCGCCGAGGCCGGGACTCAGATGTTGAAAGTTAATTTGTGTAAA
Sequence         GACTTATGCACGTGGTGACATGAGTTCTGCCCAGTGCTCTGAAATCAAAGTGAAGAAA
                 TAAATCCATGGAAGCCCAGGCAAATGATGGGTGTAGCTATGACTCTCTGAAGGACCTG
                 CAGAGAAACGCCTCCTGATTTTGTCTTACAATGGAACTTAAAAAGTCGCCTGACGGTG
                 GATGGGGCTGGGTGATTGTGTTTGTCTCCTTCCTTACTCAGTTTTTGTGTTACGGATC
                 CCCACTAGCTGTTGGAGTCCTGTACATAGAATGGCTGGATGCCTTTGGTGAAGGAAAA
                 GGAAAAACAGCCTGGGTTGGATCCCTGGCAAGTGGAGTTGGCTTGCTTGCAAGTCCTG
                 TCTGCAGTCTCTGTGTCTCATCTTTTGGAGCAAGACCTGTCACAATCTTCAGTGGCTT
                 CATGGTGGCTGGAGGCCTGATGTTGAGCAGTTTTGCTCCCAATATCTACTTTCTGTTT
                 TTTTCCTATGGCATTGTTGTAGGTCTTGGATGTGGTTTATTATACACTGCAACAGTGA
                 CCATTACGTGCCAGTATTTTGACGATCGCCGAGGCCTAGCGCTTGGCCTGATTTCAAC
                 AGGTTCAAGCGTTGGCCTTTTCATATATGCTGCTCTGCAGAGGATGCTGGTTGAGTTC
                 TATGGACTGGATGGATGCTTGCTGATTGTGGGTGCTTTAGCTTTAAATATATTAGCCT
                 GTGGCAGTCTGATGAGACCCCTCCAATCTTCTGATTGTCCTTTGCCTAAAAAAATAGC
                 TCCAGAAGATCTACCAGATAAATACTCCATTTACAATGAAAAAGGAAAGAATCTGGAA
                 GAAAACATAAACATTCTTGACAAGAGCTACAGTAGTGAGGAAAAATGCAGGATCACGT
                 TAGCCAATGGTGACTGGAAACAAGACAGCCTACTTCATAAAAACCCCACAGTGACACA
                 CACAAAAGAGCCTGAAACGTACAAAAAGAAAGTTGCAGAACAGACATATTTTTGCAAA
                 CAGCTTGCCAAGAGGAAGTGGCAGTTATATAAAAACTACTGTGGTGAAACTGTGGCTC
                 TTTTTAAAAACAAAGTATTTTCAGCCCTTTTCATTGCTATCTTACTCTTTGACATCGG
                 AGGGTTTCCACCTTCATTACTTATGGAAGATGTAGCAAGAAGTTCAAACGTGAAAGAA
                 GAAGAGTTTATTATGCCACTTATTTCCATTATAGGCATTATGACAGCAGTTGGTAAAC
                 TGCTTTTAGGGATACTGGCTGACTTCAAGTGGATTAATACCTTGTATCTTTATGTTGC
                 TACCTTAATCATCATGGGCCTAGCCTTGTGTGCAATTCCATTTGCCAAAAGCTATGTC
                 ACATTGGCGTTGCTTTCTGGGATCCTAGGGTTTCTTACTGGTAATTGGTCCATCTTTC
                 CATATGTGACCACGAAGACTGTGGGAATTGAAAAATTAGCCCATGCCTATGGGATATT
                 AATGTTCTTTGCTGGACTTGGAAATAGCCTAGGACCACCATCGTTGGGTTGGTTTTAT
                 GACTGGACCCAGACCTATGATATTGCATTTTATTTTAGTGGCTTCTGCGTCCTGCTGG
                 GAGGTTTTATTCTGCTGCTGGCAGCCTTGCCCTCTTGGGATACATGCAACAAGCAACT
                 CCCCAAGCCAGCTCCAACAACTTTCTTGTACAAAGTTGCCTCTAATGTTTAGAAGAAT
                 ATTGGAAGACACTATTTTTGCTATTTTATACCATATAGCAACGATATTTTAACAGATT
                 CTCAAGCAAATTTTCTAGAGTCAAGACTATTTTCTCATAGCAAAATTTCACAATGACT
                 GACTCTGAATGAATTATTTTTTTTTATATATCCTATTTTTTATGTAGTGTATGCGTAG
                 CCTCTATCTCGTATTTTTTTCTATTTCTCCTCCCCACACCATCAATGGGACTATTCTG
                 TTTTGCTGTTATTCACTAGTTCTTAACATTGTAAAAAGTTTGACCAGCCTCAGAAGGC
                 TTTCTCTGTGTAAAGAAGTATAATTTCTCTGCTGACTCCATTTAATCCACTGCAAGGC
                 ACCTAGAGAGACTGCTCCTATTTTAAAAGTGATGCAAGCATCATGATAAGATATGTGT
                 GAAGCCCACTAGGAAATAAATCATTCTCTTCTCTATGTTTGACTTGCTAGTAAACAGA
                 AGACTTCAAGCCAGCCAGGAAATTAAAGTGGCGACTAAAACAGCCTTAAGAATTGCAG
                 TGGAGCAAATTGGTCATTTTTTAAAAAAATATATTTTAACCTACAGTCACCAGTTTTC
                 ATTATTCTATTTACCTCACTGAAGTACTCGCATGTTGTTTGGTACCCACTGAGCAACT
                 GTTTCAGTTCCTAAGGTATTTGCTGAGATGTGGGTGAACTCCAAATGGAGAAGTAGTC
                 ACTGTAGACTTTCTTCATGGTTGACCACTCCAACCTTGCTCACTTTTGCTTCTTGGCC
                 ATCCACTCAGCTGATGTTTCCTGGAAGTGCTAATTTTACCTGTTTCCAAATTGGAAAC
                 ACATTTCTCAATCATTCCGTTCTGGCAAATGGGAAACATCCATTTGCTTTGGGCACAG
                 TGGGGATGGGCTGCAAGTTCTTGCATATCCTCCCAGTGAAGCATTTATTTGCTACTAT
                 CAGATTTTACCACTATCAAATATAATTCAAGGGCAGAATTAAACGTGAGTGTGTGTGT
                 GTGTGTGTGTGTGTGTGCTATGCATGCTCTAAGTCTGCATGGGATATGGGAATGGAAA
                 AGGGCAATAAGAAATTAATACCCTTATGCAGTTGCATTTAACCTTAAGAAAAATGTCC
                 TTGGGATAAACTCCAATGTTTAATACATTGATTTTTTTTCTAAAGAAATGGGTTTTAA
                 ACTTTGGTATGCATCAGAATTCCCTATAGATCTTTTTGAAAATATAGGTACCTGGGTA
                 TCACACATAGAACTTTTAATTCTGCTGGTGTAGGCTGTTGCCCAAACATCTATAATTT
                 TACTGAGCTCTTCAAGTGATTCTGATAACACAGCCTGGATTGAGAATTTTTATAAGAT
                 TGGCAATGGAAAAACATTTATTCTTTTAAATAATAATTTTTTTAAAACCCAAGAGGTC
                 AGGGGATTTTATAAACCAATAGCCAAGTGTTCTTTAAATAGGAGGCACCCTTCCCATT
                 GTGCCAAAATCATCTTTTCATTTATTTTGAAATTTGTATGATTATTTTATACTTGTAT
                 GTTGCCTTTCTTCGAAGGCGCCTGAAGCACTTTATAAACACAAATCCTCACAATACCT
                 CTGTGAGGTAGGTAAATAGTACTTTTCTATGTAGTAAACCTGGAATATGGAGAATTTC
                 ATAACAGTTCATTCTACTTAATAATGCAATAATGGAGCTCCAAGTTGTCTTGGACTTC
                 TACACCACACTCAGACTTCTGGAAAGTTTTCTGTACCTCATTCTTTAGTCCCTGTCAA
                 GGTTAGTAAATAAAATAAGTGACATAAAAAAAAAAAAAAAACTAAACTACTTGTTGTG
                 TTGAAAGTTCCTTTTTGCCAGTTATGTTCAGGAAACCCAATAACCTGAAAAAGTTTGA
                 CTTTGATGTGACATCTTCATATTCATCAATGCTGATAATTGTCCAAAGGCATCTTCAC
                 TATGTCTGCTAAATAACATCCAATGTGGGCGTTATCTGTTGTCTAGGGGATGAATTTT
                 AAGTTACAATAAAATATTTTTCTTTGTTTTGCATCAAAAAAAAAA
                 ORF Start: ATG at 263 ORF Stop: TAG at 1790
                 SEQ ID NO:70          509 aa MW at 55780.8 kD
NOV19a,          MELKKSPDGGWGWVIVFVSFLTQFLCYGSPLAVGVLYIEWLDAFGEGKGKTAWVGSLA
CG93088-01       SGVGLLASPVCSLCVSSFGARPVTIFSGFMVAGGLMLSSFAPNIYFLFFSYGIVVGLG
Protein Sequence CGLLYTATVTITCQYFDDRRGLALGLISTGSSVGLFIYAALQRMLVEFYGLDGCLLIV
                 GALALNILACGSLMRPLQSSDCPLPKKIAPEDLPDKYSIYNEKGKNLEENINILDKSY
                 SSEEKCRITLANGDWKQDSLLHKNPTVTHTKEPETYKKKVAEQTYFCKQLAKRKWQLY
                 KNYCGETVALFKNKVFSALFIAILLFDIGGFPPSLLMEDVARSSNVKEEEFIMPLISI
                 IGIMTAVGKLLLGILADFKWINTLYLYVATLIIMGLALCAIPFAKSYVTLALLSGILG
                 FLTGNWSIFPYVTTKTVGIEKLAHAYGILMFFAGLGNSLGPPSLGWFYDWTQTYDIAF
                 YFSGFCVLLGGFILLLAALPSWDTCNKQLPKPAPTTFLYKVASNV

[0369] 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 plasma membrane; 0.4600 probability located in
analysis: Golgi body; 0.3700 probability located in endoplasmic reticulum (membrane);
          0.1000 probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 29 and 30
analysis:

[0370] A search of the NOV1 9a 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
AAY31642	Human transport-associated protein-4	5 . . . 218	75/214 (35%)	1e−33
	(TRANP-4) - Homo sapiens, 465 aa.	14 . . . 227	116/214 (54%)
	[WO9941373-A2, 19-AUG-1999]
AAM93737	Human polypeptide, SEQ ID NO:	7 . . . 201	67/196 (34%)	5e−30
	3705 - Homo sapiens, 471 aa.	33 . . . 228	109/196 (55%)
	[EP1130094-A2, 05-SEP-2001]
AAB88570	Human hydrophobic domain	7 . . . 201	67/196 (34%)	6e−30
	containing protein clone HP03612	9 . . . 204	108/196 (54%)
	#34 - Homo sapiens, 375 aa.
	[WO200112660-A2, 22-FEB-2001]
AAE06594	Human protein having hydrophobic	67 . . . 451	95/403 (23%)	3e−25
	domain, HP03949 - Homo sapiens,	13 . . . 384	175/403 (42%)
	390 aa. [WO200149728-A2,
	12-JUL-2001]
AAO07132	Human polypeptide SEQ ID NO	398 . . . 480	38/83 (45%)	1e−14
	21024 - Homo sapiens, 107 aa.	5 . . . 87	51/83 (60%)
	[WO200164835-A2, 07-SEP-2001]

[0371] 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
Q9UFH8	HYPOTHETICAL 17.1 KDA	353 . . . 509	155/157 (98%)	2e−87
	PROTEIN - Homo sapiens	1 . . . 157	156/157 (98%)
	(Human), 157 aa (fragment).
Q9CPZ7	4930425B13RIK PROTEIN	352 . . . 509	148/159 (93%)	2e−82
	(1200003C15RIK PROTEIN) - Mus	1 . . . 159	152/159 (95%)
	musculus (Mouse), 159 aa.
O15374	Monocarboxylate transporter 5	5 . . . 473	128/487 (26%)	7e−47
	(MCT 5) (MCT 4) - Homo sapiens	13 . . . 468	222/487 (45%)
	(Human), 487 aa.
O15403	Monocarboxylate transporter 7	7 . . . 491	124/490 (25%)	3e−40
	(MCT 7) (MCT 6) - Homo sapiens	19 . . . 481	223/490 (45%)
	(Human), 523 aa.
Q9W509	MCT1 PROTEIN - Drosophila	7 . . . 230	85/227 (37%)	1e−38
	melanogaster (Fruit fly), 626 aa.	29 . . . 255	124/227 (54%)

[0372] PFam analysis indicates that the NOV19a protein contains the domains shown in Table 19E.

TABLE 19E
Domain Analysis of NOV19a
		Identities/
		Similarities
Pfam Domain	NOV19a Match Region	for the Matched Region	Expect Value
sugar_tr: domain 1 of 1	11 . . . 456	74/547 (14%)	0.27
		276/547 (50%)

Example 20

[0373] 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:71          724 bp
NOV20a,          CAGGAGGCGGGTGGGTCAAGGTAACTCTGGGCTACAGAGTCCTTGCTGGGGGTTCGGG
CG93335-01 DNA   GAGCGCTTGGACCCCGGCTTCTGGGACGCGTCAGAATATTATCCAGCAATGCAAATGA
Sequence         ACAAACTATAACTACACACAGCTGCATGGATAAATGTCAGAAACATGACGTTGAGTGT
                 GAGAAGCCAGATGCAAACGAGGACTCACTGTGCAATTCTGTGCATGTACAGTGGCCAG
                 GAGAAGGGAGCACTGGCTTTGCTTTCATCAGGCCAAAGATGCCTTTCTTTGGGAATAC
                 GTTCAGTCCGAAGAAGACACCTCCTCGGAAGTCGGCATCTCTCTCCAACCTGCATTCT
                 TTGGATCGATCAACCCGGGAGGTGGAGCTGGGCTTGGAATACGGATCCCCGACTATGA
                 ACCTGGCAGGGCAAAGCCTGAAGTTTGAAAATGGCCAGTGGATAGCAGAGACAGGGGT
                 TAGTGGCGGTGTGGACCGGAGGGAGGTTCAGCGCCTTCGCAGGCGGAACCAGCAGTTG
                 GAGGAAGAGAACAATCTCTTGCGGCTGAAAGTGGACATCTTATTAGACATGCTTTCAG
                 AGTCCACTGCTGAATCCCACTTAATGGAGAAGGAACTGGATGAACTGAGGATCAGCCG
                 GAAGAGAAAATGAAGACCCCAGAGACATTTATTGGGGAGTAGGATGTGGCTGAGTGCT
                 TTTTTTTTGGCCAGACTAGCGGATTCAG
                 ORF Start: ATG at 142 ORF Stop: TGA at 649
                 SEQ ID NO:72          169 aa MW at 19286.6 kD
NOV20a,          MDKCQKHDVECEKPDANEDSLCNSVHVQWPGEGSTGFAFIRPKMPFFGNTFSPKKTPP
CG93335-01       RKSASLSNLHSLDRSTREVELGLEYGSPTMNLAGQSLKFENGQWIAETGVSGGVDRRE
Protein Sequence VQRLRRRNQQLEEENNLLRLKVDILLDMLSESTAESHLMEKELDELRISRKRK

[0374] Further analysis of the NOV20a protein yielded the following properties shown in Table 20B.

TABLE 20B
Protein Sequence Properties NOV20a
PSort     0.4600 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
analysis:

[0375] 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		Match	the Matched	Expect
Identifier	Protein/Organism/Length [Patent #, Date]	Residues	Region	Value
AAM00955	Human bone marrow protein, SEQ	31 . . . 169	139/139 (100%)	1e−74
	ID NO: 431 - Homo sapiens, 175 aa.	37 . . . 175	139/139 (100%)
	[WO200153453-A2, 26-JUL-2001]
AAY86201	Nuclear transport protein clone	103 . . . 169	67/67 (100%)	6e−30
	hfb2025 protein sequence - Homo	1 . . . 67	67/67 (100%)
	sapiens, 67 aa. [WO9964455-A1, 16-
	DEC-1999]
ABB23535	Protein #5534 encoded by probe for	44 . . . 69	26/26 (100%)	2e−08
	measuring heart cell gene expression	1 . . . 26	26/26 (100%)
	- Homo sapiens, 26 aa.
	[WO200157274-A2, 09-AUG-2001]
AAB69070	Human male enhanced antigen-2	62 . . . 163	25/102 (24%)	1.1
	(MEA-2) protein sequence SEQ ID	768 . . . 868	45/102 (43%)
	NO:2 - Homo sapiens, 1374 aa.
	[JP2000316580-A, 21-NOV-2000]
AAU36216	Pseudomonas aeruginosa cellular	104 . . . 163	22/67 (32%)	1.9
	proliferation protein #206 -	683 . . . 749	35/67 (51%)
	Pseudomonas aeruginosa, 874 aa.
	[WO200170955-A2, 27-SEP-2001]

[0376] 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
Q9Y3M2	HYPOTHETICAL 14.5 KDA	44 . . . 169	126/126 (100%)	4e−66
	PROTEIN (CHROMOSOME 22	1 . . . 126	126/126 (100%)
	OPEN READING FRAME 2) -
	Homo sapiens (Human), 126 aa.
AAL56062	CYTOSOLIC LEUCINE-RICH	44 . . . 169	125/126 (99%)	1e−65
	PROTEIN - Homo sapiens (Human),	1 . . . 126	126/126 (99%)
	126 aa.
Q9D1C2	1110014P06RIK PROTEIN (RIKEN	44 . . . 169	104/126 (82%)	1e−56
	CDNA 1110014P06 GENE) - Mus	1 . . . 126	120/126 (94%)
	musculus (Mouse), 127 aa.
Q9UIK9	HRIHFB2025 PROTEIN - Homo	103 . . . 169	67/67 (100%)	1e−29
	sapiens (Human), 67 aa (fragment).	1 . . . 67	67/67 (100%)
Q9CVN6	1700121K02RIK PROTEIN - Mus	47 . . . 160	45/122 (36%)	2e−15
	musculus (Mouse), 226 aa	70 . . . 191	69/122 (55%)
	(fragment).

[0377] PFam analysis indicates that the NOV20a protein contains the domains shown in Table 20E.

TABLE 20E
Domain Analysis of NOV20a
		Identities/
	NOV20a	Similarities for
	Match	the Matched	Expect
Pfam Domain	Region	Region	Value
Transposase_8: domain 1 of 1	54 . . . 149	22/99 (22%)	2.9
		64/99 (65%)

Example 21

[0378] 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:73         1310 bp
NOV21a,          GATTCCAGTTGAAGTCAGTTTGACTTAATGAGCTCTTCTCTATTTTCCTACTCAAACC
CG93345-01 DNA   TCTATTCCACCATGTCACCACTCAACCAAACTACTGAGAACCACCAGAGCTTCTTCAC
Sequence         CCTGACTGGGATTCCAGGAATGCCAGAGAAAGACTTATGGATGGCCTTGCCCCTCTGT
                 CTTCTTTATAGCACCACGATCTTGGGAAATGTCACCATCCTTGTTGTCATCAAAGTTG
                 AGCAAAGTCTCCATGAGCCCATGTATTTTTTTCTAGCCATGTTAGCTGCCACTGACCT
                 CAGCCTTTCACTGTCTTCCATGCCTACCATGGTCAGTGTTCACTGGTTCAACTGGCGT
                 TCAATAACTTTTAATGGCTGCCTTATCCAGATGTTCTTCATCCACACATTTGGGGGAG
                 TGGAATCAGGTGTTCTGGTGGCCATGGCCTTTGATCGCTTTGTGGCCATCCGCTTTCC
                 TTTGCACTATGCTACAATTCTCACTCACAGTGTCATCAGCAAGATTGCAGCAGCCATC
                 CTGCTACGGAGTGTGGGGGCTGTGCTCCCTGTGCCTTTTCTCATCAAAAGGTTACCTT
                 TCTGTCACTCCAATGTCCTCTCCCATGCATACTGCCTCCATCAGGATGCCATGAGGCT
                 TGCCTGTGCTGACACTGGTGTCAATAGCATCTATGGCCTGTTGGCTGTGATCTTCATC
                 ATTGTACTAGATGCCTTAATACTTTTGGCCTCTTACATTCTAATCCTGCAGGCAGTAT
                 TGAGCATTGCTTCCCAGGAAGACAGGCTCAAGGCTCTCAACACCTGTGTCTCTCTCAT
                 ATCTGCAGTGCTGCTTTTCTATGTGCCTCTCATTGGTATGACCCTAATTCATCGCTAT
                 GGGAAGCATTTGTCACCACTAATACACACATTCATGGCCAATATCTACCTGCTTCTCC
                 CTCCTGTGCTCAATCCCATTGTGTACAGTGTTAGGACCAAGCAGATCTGATAGCAGAT
                 TGTCCAGGCCTTTTGTGGGGCTAGGGTTAGCCCTTAATGGCATCTACTATTTCCAAGT
                 AAATGCAATCAAGTTAGAGAAGAGTATCAAATACAGCACTATCCAATAGAAATTCCCA
                 CAGAAGTGGATATTTTCTATTTCTCTGCTGTTTAGTAACTAGTAGCTGTACATGGCTA
                 TTAATTGCTTGAAATTTTGCTAGTGCAAGCTGAGGAACTGAATTTTAAATGTACTTAA
                 TTTTAATTGATTTAAATGTAAATTTAAGTAGTCATATGTAACTAGTAGCTGCCGTATC
                 AAATAGTACAAATACAATGGGTAGTGATATGAAA
                 ORF Start: ATG at 28 ORF Stop: TGA at 976
                 SEQ ID NO:74         316 aa MW at 35115.4 kD
NOV21a,          MSSSLFSYSNLYSTMSPLNQTTENHQSFFTLTGIPGMPEKDLWMALPLCLLYSTTILG
CG93345-01       NVTILVVIKVEQSLHEPMYFFLAMLAATDLSLSLSSMPTMVSVHWFNWRSITFNGCLI
Protein Sequence QMFFIHTFGGVESGVLVAMAFDRFVAIRFPLHYATILTHSVISKIAAAILLRSVGAVL
                 PVPFLIKRLPFCHSNVLSHAYCLHQDAMRLACADTGVNSIYGLLAVIFIIVLDALILL
                 ASYILILQAVLSIASQEDRLKALNTCVSLISAVLLFYVPLIGMTLIHRYGKHLSPLIH
                 TFMANIYLLLPPVLNPIVYSVRTKQI

[0379] Further analysis of the NOV21a protein yielded the following properties shown in Table 21B.

TABLE 21B
Protein Sequence Properties NOV21a
PSort     0.6000 probability located in plasma membrane; 0.4905
analysis: probability located in mitochondrial inner membrane;
          0.4000 probability located in Golgi body; 0.3000
          probability located in endoplasmic reticulum (membrane)
SignalP   Cleavage site between residues 59 and 60
analysis:

[0380] 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		Match	the Matched	Expect
Identifier	Protein/Organism/Length [Patent #, Date]	Residues	Region	Value
AAG71700	Human olfactory receptor	15 . . . 316	298/302 (98%)	e−169
	polypeptide, SEQ ID NO: 1381 -	1 . . . 302	301/302 (98%)
	Homo sapiens, 323 aa.
	[WO200127158-A2, 19-APR-2001]
AAG71602	Human olfactory receptor	15 . . . 316	193/303 (63%)	c−110
	polypeptide, SEQ ID NO: 1283 -	1 . . . 302	244/303 (79%)
	Homo sapiens, 302 aa.
	[WO200127158-A2, 19-APR-2001]
AAU24684	Human olfactory receptor	15 . . . 316	193/303 (63%)	e−110
	AOLFR183 - Homo sapiens, 302 aa.	1 . . . 302	244/303 (79%)
	[WO200168805-A2, 20-SEP-2001]
AAG71516	Human olfactory receptor	26 . . . 316	170/291 (58%)	9e−99
	polypeptide, SEQ ID NO: 1197 -	11 . . . 301	220/291 (75%)
	Homo sapiens, 315 aa.
	[WO200127158-A2, 19-APR-2001]
AAU24569	Human olfactory receptor AOLFR59	26 . . . 316	170/291 (58%)	9e−99
	- Homo sapiens, 315 aa.	11 . . . 301	220/291 (75%)
	[WO200168805-A2, 20-SEP-2001]

[0381] 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
AAL60646	OLFACTORY RECEPTOR	19 . . . 316	210/298 (70%)	e−119
	MOR10-1 - Mus musculus	4 . . . 300	248/298 (82%)
	(Mouse), 315 aa.
AAL60660	OLFACTORY RECEPTOR	22 . . . 316	181/295 (61%)	e−104
	MOR10-2 - Mus musculus	7 . . . 301	228/295 (76%)
	(Mouse), 318 aa.
AAL60631	OLFACTORY RECEPTOR	13 . . . 316	172/304 (56%)	2e−98
	MOR5-2 - Mus musculus	5 . . . 307	232/304 (75%)
	(Mouse), 321 aa.
AAL60629	OLFACTORY RECEPTOR	13 . . . 316	173/304 (56%)	2e−98
	MOR5-1 - Mus musculus	5 . . . 307	230/304 (74%)
	(Mouse), 321 aa.
AAL60640	OLFACTORY RECEPTOR	27 . . . 316	170/290 (58%)	1e−97
	MOR7-2 - Mus musculus	13 . . . 302	221/290 (75%)
	(Mouse), 312 aa.

[0382] PFam analysis indicates that the NOV21a protein contains the domains shown in Table 21E.

TABLE 21E
Domain Analysis of NOV21a
		Identities/
		Similarities
Pfam Domain	NOV21a Match Region	for the Matched Region	Expect Value
7tm_1: domain 1 of 1	58 . . . 309	50/270 (19%)	1.2e−22
		169/270 (63%)

Example 22

[0383] 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:75         999 bp
NOV22a,          ACGAGTGGATAAGCTAGTGACCTATCTGTGATGTTTCTGCTCAATACCTCAGAAGTTG
CG93400-01 DNA   AAGTCTCCACATTCCTATTGATTGGGATACCAGGACTTGAGCATGCACACATTTGGAT
Sequence         CTCTATCCCCATCTGCCTTATGTACCTCATGGCCATCCTGGGCAACTGCACCATCCTA
                 TTTGTTATCAGAACAGAGCATTCCCTGCAAGAGCCCATGTACTATTTCCTCTCCATGC
                 TGGCCCTGTCCGACCTGGGCCTGTCTTTCTCCTCCCTACCCACGATGCTGAGAATCTT
                 CTTGTTCAACAACATGGGGATTTCTGCTGATACATGCATTGCCCAGGAATTCTTCATC
                 CATGGATTCACAGACATGGAGTCTTCAGTTCTCCTAATCATGTCCTTTGATCACTTAG
                 TAGCCATTTGCAACCCCCTAAGATATAGCTCTATTCTCACCAGCTTCAGGGTTTTGCA
                 AATTGGACTGGCTTTTGCCATTAAAAGCATTCTCCTAGTGCTACCCCTTCCTTTTACT
                 TTAAAGAGACTCAGATACTGTAATAAACACCTTTTATCCCACTCCTACTGCCTTCACC
                 AGGATGTAATGAAGCTGGCCTGCTCTGACAACAGGGTTAACTTTTACTATGGTTTGTT
                 CGTTGCACTCTGCATGATGTCAGACAGTTTTTATTGCTATTTCCTATATGTGTTCATC
                 CTGAAGACTGTGTTGGGTATTGCATCCCATGGGGAGTGCCTCGAAGCTCTTGACACCT
                 GTGTGTCTCATATCTGTGCTGTACTCGTCTTCTATGTGCCCATCATCACCTTGGCTAC
                 CATGCGTCGCTTTGCTAAGCATAAATCCCCTTTAGCTATGATTCTGATAGCAGATGCA
                 TTCTTGCTGGTACCACCCTTGATGAATCCCATTGTGTATTGTGTAAAAACTCGGCAGA
                 TTAGAGTAAAGGTCCTGGAAAAATTGGCTCTGAAGCCTAAATGATGGGGCAAAGGTGG
                 AAATTCTATTTTT
                 ORF Start: ATG at 31 ORF Stop: TGA at 970
                 SEQ ID NO:76         313 aa MW at 35541.3 kD
NOV22a,          MFLLNTSEVEVSTFLLIGIPGLEHAHIWISIPICLMYLMAILGNCTILFVIRTEHSLQ
CG93400-01       EPMYYFLSMLALSDLGLSFSSLPTMLRIFLFNNMGISADTCIAQEFFIHGFTDMESSV
Protein Sequence LLIMSFDHLVAICNPLRYSSILTSFRVLQIGLAFAIKSILLVLPLPFTLKRLRYCNKH
                 LLSHSYCLHQDVMKLACSDNRVNFYYGLFVALCMMSDSFYCYFLYVFILKTVLGIASH
                 GECLEALDTCVSHICAVLVFYVPIITLATMRRFAKHKSPLAMILIADAFLLVPPLMNP
                 IVYCVKTRQIRVKVLEKLALKPK

[0384] Further analysis of the NOV22a protein yielded the following properties shown in Table 22B.

TABLE 22B
Protein Sequence Properties NOV22a
PSort     0.6000 probability located in plasma membrane;
analysis: 0.4000 probability located in Golgi body; 0.3000 probability
          located in endoplasmic reticulum (membrane);
          0.2414 probability located in mitochondrial inner membrane
SignalP   Cleavage site between residues 44 and 45
analysis:

[0385] 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 Results for NOV22a
		NOV22a	Identities/
		Residues/	Similarities for
Geneseq		Match	the Matched	Expect
Identifier	Protein/Organism/Length [Patent #, Date]	Residues	Region	Value
AAG71721	Human olfactory receptor	1 . . . 313	305/314 (97%)	e−172
	polypeptide, SEQ ID NO: 1402 -	1 . . . 313	307/314 (97%)
	Homo sapiens, 316 aa.
	[WO200127158-A2, 19-APR-2001]
AAG71564	Human olfactory receptor	1 . . . 311	231/311 (74%)	e−131
	polypeptide, SEQ ID NO: 1245 -	5 . . . 315	264/311 (84%)
	Homo sapiens, 322 aa.
	[WO200127158-A2, 19-APR-2001]
AAG71701	Human olfactory receptor	1 . . . 308	230/308 (74%)	e−129
	polypeptide, SEQ ID NO: 1382 -	1 . . . 306	257/308 (82%)
	Homo sapiens, 312 aa.
	[WO200127158-A2, 19-APR-2001]
AAU24682	Human olfactory receptor	1 . . . 308	230/308 (74%)	e−129
	AOLFR181 - Homo sapiens, 312 aa.	1 . . . 306	257/308 (82%)
	[WO200168805-A2, 20-SEP-2001]
AAG72486	Human OR-like polypeptide query	1 . . . 313	234/338 (69%)	e−127
	sequence, SEQ ID NO: 2167 - Homo	1 . . . 338	265/338 (78%)
	sapiens, 345 aa. [WO200127158-A2,
	19-APR-2001]

[0386] 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
AAL60639	OLFACTORY RECEPTOR	3 . . . 313	273/311 (87%)	e−154
	MOR8-3 - Mus musculus	2 . . . 312	286/311 (91%)
	(Mouse), 312 aa.
AAL60635	OLFACTORY RECEPTOR	1 . . . 311	248/311 (79%)	e−141
	MOR8-1 - Mus musculus	8 . . . 318	271/311 (86%)
	(Mouse), 318 aa.
AAL60638	OLFACTORY RECEPTOR	1 . . . 311	214/311 (68%)	e−121
	MOR8-2 - Mus musculus	5 . . . 315	252/311 (80%)
	(Mouse), 317 aa.
AAL60640	OLFACTORY RECEPTOR	12 . . . 304	175/294 (59%)	1e−94
	MOR7-2 - Mus musculus	13 . . . 306	215/294 (72%)
	(Mouse), 312 aa.
AAL60634	OLFACTORY RECEPTOR	1 . . . 307	171/308 (55%)	4e−94
	MOR7-1 - Mus musculus	1 . . . 308	221/308 (71%)
	(Mouse), 313 aa.

[0387] PFam analysis indicates that the NOV22a protein contains the domains shown in Table 22E.

TABLE 22E
Domain Analysis of NOV22a
		Identities/
		Similarities
Pfam Domain	NOV22a Match Region	for the Matched Region	Expect Value
7tm_1: domain 1 of 2	43 . . . 81	12/39 (31%)	6e−09
		30/39 (77%)
7tm_1: domain 2 of 2	217 . . . 293	13/88 (15%)	1.3
		51/88 (58%)

Example 23

[0388] 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:77        2715 bp
NOV23a,           GATGGAGCACGGCACACTCCTCGCCCAGCCCGGGCTCTGGACCAGGGACACCAGCTGG
CG93410-01 DNA    GCACTCCTCTATTTCCTCTGCTATATCCTCCCTCAGACCGCCCCGCAAGTACTCAGGA
Sequence          TCGGAGGGATTTTTGAAACAGTGGAAAATGAGCCTGTTAATGTTGAAGAATTAGCTTT
                  CAAGTTTGCAGTCACCAGCATTAACAGAAACCGAACCCTGATGCCTAACACCACATTA
                  ACCTATGACATCCAGAGAATTAACCTTTTTGATAGTTTTGAGGCCTCGCGGAGAGCAT
                  GTGACCAGCTGGCTCTTGGTGTGGCTGCTCTCTTTGGCCCTTCCCATAGCTCCTCCGT
                  CAGTGCTGTGCAGTCTATTTGCAATGCTCTCGAAGTTCCACACATACAGACCCGCTGG
                  AAACACCCCTCGGTGGACAACAAAGATTTGTTTTACATCAACCTTTACCCAGATTATG
                  CAGCTATCAGCAGGGCGATCCTGGATCTGGTCCTCTATTACAACTGGAAAACAGTGGC
                  AGTGGTGTATGAAGACAGCACAGGTCTAATTCGTCTACAAGAGCTCATCAAAGCTCCC
                  TCCAGATATAATATTAAAATCAAAATCCGCCAGCTGCCCTCTGGGAATAAAGATGCCA
                  AGCCTTTACTCAAGGAGATGAAGAAAGGCAAGGAGTTCTATGTGATATTTGATTGTTC
                  ACATGAAACAGCCGCTGAAATCCTTAAGCAGATTCTGTTCATGGGCATGATGACCGAG
                  TACTATCACTACTTTTTCACAACCCTGGACTTATTTGCTTTGGATCTGGAACTCTATA
                  GGTACAGTGGCGTAAACATGACCGGGTTTCGGCTGCTTAACATTGACAACCCTCACGT
                  GTCATCCATCATTGAGAAGTGGTCCATGGAGAGACTGCAGGCCCCACCCAGGCCCGAG
                  ACTGGCCTTTTGGATGGCATGATGACAACTGAAGCGGCTCTGATGTACGATGCTGTGT
                  ACATGGTGGCCATTGCCTCGCACCGGGCATCCCAGCTGACCGTCAGCTCCCTGCAGTG
                  CCATAGACATAAGCCATGGCGCCTCGGACCCAGATTTATGAACCTGATCAAAGAGGCC
                  CGGTGGGATGGCTTGACTGGGCATATCACCTTTAATAAAACCAATGGCTTGAGGAAGG
                  ATTTTGATCTGGATATTATTAGTCTCAAAGAGGAAGGAACTGAAAAGATTGGGATTTG
                  GAATTCCAACAGTGGGCTTAACATGACGGACAGCAACAAAGACAAGTCCAGCAATATC
                  ACTGATTCATTGGCCAACAGAACACTCATTGTCACCACCATTCTGGAAGAACCCTATG
                  TTATGTACAGGAAATCTGATAAGCCTCTATATGGAAATGACAGATTTGAAGGATATTG
                  CCTAGACCTGTTGAAAGAATTGTCAAACATCCTGGGTTTCATTTATGATGTTAAACTA
                  GTTCCCGATGGCAAATATGGGGCCCAGAATGACAAAGGGGAGTGGAACGGGATGGTTA
                  AAGAACTCATAGATCACAGGGCTGACCTGGCAGTGGCTCCTCTTACCATCACCTACGT
                  GCGGGAGAAAGTCATTGACTTCTCCAAACCCTTCATGACCCTAGGCATCAGCATTCTC
                  TACCGGAAGCCCAATGGTACCAATCCAGGCGTTTTCTCCTTCCTCAACCCCCTGTCTC
                  CAGATATTTGGATGTATGTGCTCTTAGCCTGCTTGGGAGTCAGCTGTGTACTCTTTGT
                  GATTGCAAGGTTTACACCCTACGAGTGGTATAACCCCCACCCATGCAACCCTGACTCA
                  GACGTGGTGGAAAACAATTTTACTTTACTAAATAGTTTCTGGTTTGGAGTTGGAGCTT
                  TCATGCAGCAAGGATCAGAGCTGATGCCCAAAGCTCTATCGACCAGAATAGTTGGAGG
                  GATATGGTGGTTTTTCACCCTAATCATCATTTCATCCTACACGGCCAATCTGGCTGCC
                  TTCTTGACAGTAGAGAGAATGGAATCCCCCATAGATTCGGCAGATGATCTGGCAAAGC
                  AAACCAAGATAGAATATGGGGCGGTTAGAGATGGATCAACAATGACCTTCTTCAAGAA
                  ATCAAAAATCTCCACCTATGAGAAGATGTGGGCTTTCATGAGCAGCAGGCAGCAGACC
                  GCCCTGGCAAGAAACAGTGATGAGGGGATCCAGAGAGTGCTCACCACAGACTACGCGC
                  TGCTGATGGAGTCCACCAGCATTGAGTATGTGACGCAGAGAAACTGCAACCTCACTCA
                  GATCGGGGGCCTCATTGACTCCAAAGGTTACGGAGTGGGAACACCTATTGGTTCTCCT
                  TACCGGGATAAAATTACTATTGCTATTCTTCAACTCCAAGAAGAAGGGAAGCTGCATA
                  TGATGAAAGAGAAGTGGTGGCGTGGGAATGGCTGCCCCGAGGAAGACAACAAAGAAGC
                  CAGTGCCCTGGGAGTGGAAAATATTGGAGGCATCTTCATTGTTCTGGCTGCCGGACTG
                  GTCCTTTCTGTATTTGTAGCTATTGGAGAATTCATATACAAATCACGGAAGAATAATG
                  ATATTGAACAGGCTTTTTGTTTCTTTTATGGACTGCAATGTAAGCAAACCCATCCAAC
                  CAACTCCACTTCTGGAACTACTTTATCTACGGATTTAGAATGTGGTAAATTAATTCGA
                  GAGGAGAGAGGGATTCGAAAACAGTCCTCAGTTCATACTGTGTAATC
                  ORF Start: ATG at 2 ORF Stop: TAA at 2711
                  SEQ ID NO:78        903 aa MW at 102229.3 kD
NOV23a,           MEHGTLLAQPGLWTRDTSWALLYFLCYILPQTAPQVLRIGGIFETVENEPVNVEELAF
CG93410-01        KFAVTSINRNRTLMPNTTLTYDIQRINLFDSFEASRRACDQLALGVAALFGPSHSSSV
Protein Sequence  SAVQSICNALEVPHIQTRWKHPSVDNKDLFYINLYPDYAAISRAILDLVLYYNWKTVA
                  VVYEDSTGLIRLQELIKAPSRYNIKIKIRQLPSGNKDAKPLLKEMKKGKEFYVIFDCS
                  HETAAEILKQILFMGMMTEYYHYFFTTLDLFALDLELYRYSGVNMTGFRLLNIDNPHV
                  SSIIEKWSMERLQAPPRPETGLLDGMMTTEAALMYDAVYMVAIASHRASQLTVSSLQC
                  HRHKPWRLGPRFMNLIKEARWDGLTGHITFNKTNGLRKDFDLDIISLKEEGTEKIGIW
                  NSNSGLNMTDSNKDKSSNITDSLANRTLIVTTILEEPYVMYRKSDKPLYGNDRFEGYC
                  LDLLKELSNILGFIYDVKLVPDGKYGAQNDKGEWNGMVKELIDHRADLAVAPLTITYV
                  REKVIDFSKPFMTLGISILYRKPNGTNPGVFSFLNPLSPDIWMYVLLACLGVSCVLFV
                  IARFTPYEWYNPHPCNPDSDVVENNFTLLNSFWFGVGAFMQQGSELMPKALSTRIVGG
                  IWWFFTLIIISSYTANLAAFLTVERMESPIDSADDLAKQTKIEYGAVRDGSTMTFFKK
                  SKISTYEKMWAFMSSRQQTALARNSDEGIQRVLTTDYALLMESTSIEYVTQRNCNLTQ
                  IGGLIDSKGYGVGTPIGSPYRDKITIAILQLQEEGKLHMMKEKWWRGNGCPEEDNKEA
                  SALGVENIGGIFIVLAAGLVLSVFVAIGEFIYKSRKNNDIEQAFCFFYGLQCKQTHPT
                  NSTSGTTLSTDLECGKLIREERGIRKQSSVHTV
                  SEQ ID NO:79        1602 bp
NOV23b,           AGATCTCAAGTACTCAGGATCGGAGGGATTTTTGAAACAGTGGAAAATGAGCCTGTTA
188822752 DNA     ATGTTGAAGAATTAGCTTTCAAGTTTGCAGTCACCAGCATTAACAGAAACCGAACCCT
Sequence          GATGCCTAACACCACATTAACCTATGACATCCACAGAATTAACCTTTTTGATAGTTTT
                  GAGGCCTCGCGGAGAGCATGTGACCAGCTGGCTCTTGGTGTGGCTGCTCTCTTTGGCC
                  CTTCCCATAGCTCCTCCGTCAGTGCTGTGCAGTCTATTTGCAATGCTCTCGAAGTTCC
                  ACACATACAGACCCGCTGGAAACACCCCTCGGTGGACAACAAAGATTTGTTTTACATC
                  AACCTTTACCCAGATTATGCAGCTATCAGCAGGGCGATCCTGGATCTGGTCCTCTATT
                  ACAACTGGAAAACAGTGACAGTGGTGTATGAAGACAGCACAGGTCTAATTCGTCTACA
                  AGAGCTCATCAAAGCTCCCTCCAGATATAATATTAAAATCAAAATCCGCCAGCTGCCC
                  TCTGGGAATAAAGATGCCAAGCCTTTACTCAAGGAGATGAAGAAAGGCAAGGAGTTCT
                  ATGTGATATTTGATTGTTCACATGAAACAGCCGCTGAAATCCTTAAGCAGATTCTGTT
                  CATGGGCATGATGACCGAGTACTATCACTACTTTTTCACAACCCTGGACTTATTTGCT
                  TTGGATCTGGAACTCTATAGGTACAGTGGCGTAAACATGACCGGGTTTCGGCTGCTTA
                  ACATTGACAACCCTCACGTGTCATCCATCATTGAGAAGTGGTCCATGGAGAGACTGCA
                  GGCCCCACCCAGGCCCGAGACTGGCCTTTTGGATGGCATGATGACAACTGAAGCGGCT
                  CTGATGTACGATGCTGTGTACATGGTGGCCATTGCCTCGCACCGGGCATCCCAGCTGA
                  CCGTCAGCTCCCTGCAGTGCCATAGACATAAGCCATGGCGCCTCGGACCCAGATTTAT
                  GAACCTGATCAAAGAGGCCCGGTGGGATGGCTTGACTGGGCATATCACCTTTAATAAA
                  ACCAATGGCTTGAGGAAGGATTTTGATCTGGATATTATTAGTCTCAAAGAGGAAGGAA
                  CTGAAAAGATTGGGATTTGGAATTCCAACAGTGGGCTTAACATGACGGACAGCAACAA
                  AGACAAGTCCAGCAATATCACTGATTCATTGGCCAACAGAACACTCATTGTCACCACC
                  ATTCTGGAAGAACCCTATGTTATGTACAGGAAATCTGATAAGCCTCTATATGGAAATG
                  ACAGATTTGAAGGATATTGCCTAGACCTGTTGAAAGAATTGTCAAACATCCTGGGTTT
                  CATTTATGATGTTAAACTAGTTCCCGATGGCAAATATGGGGCCCAGAATGACAAAGGG
                  GAGTGGAACGGGATGGTTAAAGAACTCATAGATCACAGGGCTGACCTGGCAGTGGCTC
                  CTCTTACCATCACCTACGTGCGGGAGAAAGTCATTGACTTCTCCAAACCCTTCATGAC
                  CCTAGGCATCAGCATTCTCTACCGGAAGCCCAATGGTACCAATCCAGGCGTTTTCTCC
                  TTCCTCAACCCCCTGTCTCCAGATATTTGGCTCGAG
                  ORF Start: at 1     ORF Stop: end of sequence
                  SEQ ID NO:80        534 aa MW at 60947.3 kD
NOV23b,           RSQVLRIGGIFETVENEPVNVEELAFKFAVTSINRNRTLMPNTTLTYDIQRINLFDSF
188822752 Protein EASRRACDQLALGVAALFGPSHSSSVSAVQSICNALEVPHIQTRWKHPSVDNKDLFYI
Sequence          NLYPDYAAISRAILDLVLYYNWKTVTVVYEDSTGLIRLQELIKAPSRYNIKIKIRQLP
                  SGNKDAKPLLKEMKKGKEFYVIFDCSHETAAEILKQILFMGMMTEYYHYFFTTLDLFA
                  LDLELYRYSGVNMTGFRLLNIDNPHVSSIIEKWSMERLQAPPRPETGLLDGMMTTEAA
                  LMYDAVYMVAIASHRASQLTVSSLQCHRNKPWRLGPRFMNLIKEARWDGLTGHITFNK
                  TNGLRKDFDLDIISLKEEGTEKIGIWNSNSGLNMTDSNKDKSSNITDSLANRTLIVTT
                  ILEEPYVMYRKSDKPLYGNDRFEGYCLDLLKELSNILGFIYDVKLVPDGKYGAQNDKG
                  EWNGMVKELIDHRADLAVAPLTITYVREKVIDFSKPFMTLGISILYRKPNGTNPGVFS
                  FLNPLSPDIWLE

[0389] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 23B.

TABLE 23B
Comparison of NOV23a against NOV23b.
	NOV23a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV23b	35 . . . 565	492/531 (92%)
	3 . . . 533	493/531 (92%)

[0390] Further analysis of the NOV23a protein yielded the following properties shown in Table 23C.

TABLE 23C
Protein Sequence Properties NOV23a
PSort     0.6000 probability located in plasma membrane;
analysis: 0.4000 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 35 and 36
analysis:

[0391] 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 23D.

TABLE 23D
Geneseq Results for NOV23a
		NOV23a	Identities/
		Residues/	Similarities for
Geneseq		Match	the Matched	Expect
Identifier	Protein/Organism/Length [Patent #, Date]	Residues	Region	Value
AAR63069	Human EAA3c excitatory amino	1 . . . 862	853/862 (98%)	0.0
	acid receptor - Homo sapiens, 865	1 . . . 862	853/862 (98%)
	aa. [CA2110933-A, 12-JUN-1994]
AAB19496	The Q591 form of the human EAA3	1 . . . 858	851/858 (99%)	0.0
	receptor - Homo sapiens, 905 aa.	1 . . . 858	851/858 (99%)
	[US6136544-A, 24-OCT-2000]
AAR75883	Human EAA3 receptor (Q-591) -	1 . . . 858	851/858 (99%)	0.0
	Homo sapiens, 905 aa.	1 . . . 858	851/858 (99%)
	[WO9517508-A2, 29-JUN-1995]
AAR60112	Human EAA3a excitatory amino	1 . . . 858	851/858 (99%)	0.0
	acid receptor - Homo sapiens, 905	1 . . . 858	851/858 (99%)
	aa. [CA2110933-A, 12-JUN-1994]
AAB19499	Amino acid sequence of the R591	1 . . . 858	850/858 (99%)	0.0
	form of the human EAA3 receptor -	1 . . . 858	851/858 (99%)
	Homo sapiens, 905 aa. [US6136544-
	A, 24-OCT-2000]

[0392] 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 23E.

TABLE 23E
Public BLASTP Results for NOV23a
		NOV23a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P39086	Glutamate receptor, ionotropic kainate	1 . . . 903	900/918 (98%)	0.0
	1 precursor (Glutamate receptor 5)	1 . . . 918	900/918 (98%)
	(GLUR-5) (GluR5) (Excitatory amino
	acid receptor 3) (EAA3) - Homo
	sapiens (Human), 918 aa.
CAC80546	GLUTAMATE RECEPTOR	1 . . . 858	852/858 (99%)	0.0
	SUBUNIT GLUR5 - Homo sapiens	1 . . . 858	852/858 (99%)
	(Human), 905 aa.
P22756	Glutamate receptor, ionotropic kainate	1 . . . 854	823/869 (94%)	0.0
	1 precursor (Glutamate receptor 5)	1 . . . 869	838/869 (95%)
	(GLUR-5) (GluR5) - Rattus
	norvegicus (Rat), 949 aa.
Q9DGM1	GLUTAMATE RECEPTOR 5 - Danio	32 . . . 854	735/837 (87%)	0.0
	aequipinnatus (Giant danio)	32 . . . 868	789/837 (93%)
	(Brachydanio aequipinnatus), 880 aa.
Q60934	Glutamate receptor, ionotropic kainate	1 . . . 756	707/758 (93%)	0.0
	1 precursor (Glutamate receptor 5)	1 . . . 758	727/758 (95%)
	(GLUR-5) (GluR5) - Mus musculus
	(Mouse), 836 aa.

[0393] PFam analysis indicates that the NOV23a protein contains the domains shown in Table 23F.

TABLE 23F
Domain Analysis of NOV23a
		Identities/
		Similarities
	NOV23a Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
ANF_receptor: domain 1 of 1	25 . . . 415	95/466 (20%)	8.9e−114
		351/466 (75%)
SBP_bac_3: domain 1 of 1	434 . . . 801	46/425 (11%)	0.79
		216/425 (51%)
lig_chan: domain 1 of 1	560 . . . 841	161/322 (50%)	4.8e−161
		272/322 (84%)

Example 24

[0394] 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:81         1443 bp
NOV24a,          AGCATTACCCTACTCCTAGAGGGATTGTAGAGATTAGTGCCATCATCAAGGACTTCAA
CG93722-01 DNA   AGATGCCAGAGTGGCTAGATGCAATGGGTCGTGCCTGTAATCCCAACACTTTGGGAGG
Sequence         CCAAGGCAGGAGGATTGCTTGAGGTCAGGAGTTTGAGCTTGGGCAACATAGTGAGACT
                 CTGCCTCTACAAAAAGTCTTTGAAAAAAGATACCAGAGTGGTGATTCCTAAAACATCC
                 CCATTTAGTTTGCCTATTTGGCAGAAGACAGATGGATCTTGGAGAAGACTCCACTGCA
                 CTTCCACCACCAGTGCACACACACATGGACCCAGCTGCACTGCTGCCCTGCTACTGCT
                 GGCACATGCACACGATTGTGGAACAGCACCGCTTAAGGATGTGTTGCAAGGGTCTCGG
                 ATTATAGGGGGCACCGAAGCACAAGCTGGCGCATGGCCGTGGGTGGTGAGCCTGCAGA
                 TTAAATATGGCCGTGTTCTTGTTCATGTATGTGGGGGAACCCTAGTGAGAGAGAGGTG
                 GGTCCTCACAGCTGCCCACTGCACTAAAGACACTAGGTACGTATTCAGAACACAACTA
                 TTTAGCGATCCTTTAATGTGGACAGCTGTGATTGGAACTAATAATATACATGGACGCT
                 ATCCTCATACCAAGAAGATAAAAATTAAAGCAATCATTATTCATCCAAACTTCATTTT
                 GGAATCTTATGTAAATGATATTGCACTTTTTCACTTAAAAAAAGCAGTGAGGTATAAT
                 GACTATATTCAGCCTATTTGCCTACCTTTTGATGTTTTCCAAATCCTGGACGGAAACA
                 CAAAGTGTTTTATAAGTGGCTGGGGAAGAACAAAAGAAGAAGGTAATTTGCAGCCGCT
                 TTGTTTACCTACTCAAGCCTCCGCAATGGTGTGCTCCAAGATAACTTACTGGTATTTT
                 TTGTTAACAGGTAACGCTACAAATATTTTACAAGATGCAGAAGTGCATTATATTTCTC
                 GAGAGATGTGTAATTCTGAGAGGAGTTATGGGGGAATAATTCCTAACACTTCATTTTG
                 TGCAGGTGATGAAGATGGAGCTTTTGATACTTGCAGGGGTGACAGTGGGGGACCATTA
                 ATGTGCTACTTACCAGAATATAAAAGATTTTTTGTAATGGGAATTACCAGTTACGGAC
                 ATGGCTGTGGTCGAAGAGGTTTTCCTGGTGTCTATATTGGGCCATCCTTCTACCAAAA
                 GTGGCTGACAGAGCATTTCTTCCATGCAAGCACTCAAGGCATACTTACTATAAATATT
                 TTACGTGGCCAGATCCTCATAGCTTTATGTTTTGTCATCTTACTAGCAACAACATAAA
                 GAAATTCTGAAGGCTTTCATATCTTTATTTTGCATTGTGTCCCTTTCTATGTTCTATA
                 TAATGAACATCATTTATTCTTCTAGCAATTAATTGCCTACATTAGAGATTT
                 ORF Start: ATG at 77 ORF Stop: TAA at 1331
                 SEQ ID NO:82         418 aa MW at 46709.8 kD
NOV24a,          MQWVVPVIPTLWEAKAGGLLEVRSLSLGNIVRLCLYKKSLKKDTRVVIPKTSPFSLPI
CG93722-01       WQKTDGSWRRLHCTSTTSAHTHGPSCTAALLLLAHAHDCGTAPLKDVLQGSRIIGGTE
Protein Sequence AQAGAWPWVVSLQIKYGRVLVHVCGGTLVRERWVLTAAHCTKDTRYVFRTQLFSDPLM
                 WTAVIGTNNIHGRYPHTKKIKIKAIIIHPNFILESYVNDIALFHLKKAVRYNDYIQPI
                 CLPFDVFQILDGNTKCFISGWGRTKEEGNLQPLCLPTQASAMVCSKITYWYFLLTGNA
                 TNILQDAEVHYISREMCNSERSYGGIIPNTSFCAGDEDGAFDTCRGDSGGPLMCYLPE
                 YKRFFVMGITSYGHGCGRRGFPGVYIGPSFYQKWLTEHFFHASTQGILTINILRGQIL
                 IALCFVILLATT

[0395] Further analysis of the NOV24a protein yielded the following properties shown in Table 24B.

TABLE 24B
Protein Sequence Properties NOV24a
PSort     0.9325 probability located in endoplasmic reticulum
analysis: (membrane); 0.6976 probability located in plasma
          membrane; 0.3200 probability located in microbody
          (peroxisome); 0.1900 probability located in Golgi body
SignalP   Cleavage site between residues 17 and 18
analysis:

[0396] 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 24C.

TABLE 24C
Geneseq Results for NOV24a
		NOV24a	Identities/
		Residues/	Similarities for
Geneseq		Match	the Matched	Expect
Identifier	Protein/Organism/Length [Patent #, Date]	Residues	Region	Value
AAU03900	Human protease-like polypeptide #2	92 . . . 418	288/327 (88%)	e−168
	- Homo sapiens, 348 aa.	59 . . . 348	288/327 (88%)
	[WO200149864-A1, 12-JUL-2001]
AAU03901	Human protease-like polypeptide #3	96 . . . 418	284/323 (87%)	e−166
	- Homo sapiens, 288 aa.	3 . . . 288	285/323 (87%)
	[WO200149864-A1, 12-JUL-2001]
AAU03899	Human protease-like polypeptide #1	174 . . . 418	217/245 (88%)	e−126
	- Homo sapiens, 217 aa.	1 . . . 217	217/245 (88%)
	[WO200149864-A1, 12-JUL-2001]
AAW96812	A mouse serine protease called	56 . . . 397	119/398 (29%)	4e−41
	hepsin - Mus musculus, 416 aa.	62 . . . 414	178/398 (43%)
	[WO9854307-A1, 03-DEC-1998]
AAY43325	Mouse hepsin protein sequence -	56 . . . 397	119/398 (29%)	4e−41
	Mus musculus, 416 aa.	62 . . . 414	178/398 (43%)
	[US5981830-A, 09-NOV-1999]

[0397] 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 24D.

TABLE 24D
Public BLASTP Results for NOV24a
		NOV24a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
AAL50817	AIRWAY TRYPSIN-LIKE	96 . . . 385	104/290 (35%)	1e−42
	PROTEASE - Rattus norvegicus	171 . . . 413	146/290 (49%)
	(Rat), 417 aa.
Q29015	PREPROACROSIN - Sus sp, 415	85 . . . 383	116/318 (36%)	2e−42
	aa.	4 . . . 283	150/318 (46%)
P08001	Acrosin precursor (EC 3.4.21.10)	85 . . . 383	116/318 (36%)	2e−42
	(53 kDa fucose-binding protein) -	4 . . . 283	150/318 (46%)
	Sus scrofa (Pig), 415 aa.
Q9QZ74	ADRENAL SECRETORY SERINE	96 . . . 385	104/290 (35%)	3e−42
	PROTEASE PRECURSOR - Rattus	33 . . . 275	145/290 (49%)
	norvegicus (Rat), 279 aa.
O35453	Serine protease hepsin (EC 3.4.21.-)	84 . . . 397	104/324 (32%)	2e−40
	- Mus musculus (Mouse), 416 aa.	139 . . . 414	156/324 (48%)

[0398] PFam analysis indicates that the NOV24a protein contains the domains shown in Table 24E.

TABLE 24E
Domain Analysis of NOV24a
		Identities/
		Similarities
Pfam Domain	NOV24a Match Region	for the Matched Region	Expect Value
trypsin: domain 1 of 2	111 . . . 263	67/174 (39%)	1.2e−41
		115/174 (66%)
trypsin: domain 2 of 2	287 . . . 383	41/105 (39%)	4.1e−25
		72/105 (69%)

Example 25

[0399] 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:83          2867 bp
NOV25a,          TCATTTTAGGGGCTCTGTTTTCATCTCAGATTATTCTGTCTTGTAGCCCATGGTAACT
CG93858-01 DNA   GGAGTCCTTGGAGTGGCTGGGGAACATGCAGCCGGACGTCTAACGGAGGGCAGATGCG
Sequence         GCGGTACCGCACATGTGATAACCCTCCTCCCTCCAATGGGGGAAGAGCTTGTGGGGGA
                 CCAGACTCCCAGATCCAGAGGTGCAACACTGACATGTGTCCTGTGGATGGAAGTTGGG
                 GAAGCTGGCATAGTTGGAGCCAGTGCTCTGCCTCCTGTGGAGGAGGTGAAAAGACTCG
                 GAAGCCGCTGTGCGACCATCCTGTGCCAGTTAAAGGTGGCCGTCCTTGTCCCGGAGAC
                 ACTACTCAGGTGACCAGGTGCAATGTACAAGCATGTCCAGCTCGGCCCCAGCGAGCCA
                 GAGGAAGTGTTATTGGAAATATTAATGATGTTGAATTTGGAATTGCTTTCCTTAATGC
                 CACAATAACTGATAGCCCTAACTCTGATACTAGAATAATACGTGCCAAAATTACCAAT
                 GTACCTCGTAGTCTTGGTTCAGCAATGAGAAAGATAGTTTCTATTCTAAATCCCATTT
                 ATTGGACAACAGCAAAGGAAATAGGAGAAGCAGTCAATGGCTTTACCCTCACCAATGC
                 AGTCTTCAAAAGAGAAACTCAAGTGGAATTTGCAACTGGAGAAATCTTGCAGATGAGT
                 CATATTGCCCGGGGCTTGGATTCCGATGGTTCTTTGCTGCTAGATATCGTTGTGAGTG
                 GCTATGTCCTACAGCTTCAGTCACCTGCTGAAGTCACTGTAAAGGATTACACAGAGGA
                 CTACATTCAAACAGGTCCTGGGCAGCTGTACGCCTACTCAACCCGGCTGTTCACCATT
                 GATGGCATCAGCATCCCATACACATGGAACCACACCGTTTTCTATGATCAGGCACAGG
                 GAAGAATGCCTTTCTTGGTTGAAACACTTCATGCATCCTCTGTGGAATCTGACTATAA
                 CCAGATAGAAGAGACACTGGGTTTTAAAATTCATGCTTCAATATCCAAAGGAGATCGC
                 AGTAATCAGTGCCCCTCCGGGTTTACCTTAGACTCAGTTGGACCTTTTTGTGCTGATG
                 AGGATGAATGTGCAGCAGGGAATCCCTGCTCCCATAGCTGCCACAATGCCATGGGGAC
                 TTACTACTGCTCCTGCCCTAAAGGCCTCACCATAGCTGCAGATGGAAGAACTTGTCAA
                 GATATTGATGAGTGTGCTTTGGGTAGGCATACCTGCCACGCTGGTCAGGACTGTGACA
                 ATACGATTGGATCTTATCGCTGTGTGGTCCGTTGTGGAAGTGGCTTTCGAAGAACCTC
                 TGATGGGCTGAGTTGTCAAGATATTAATGAATGTCAAGAATCCAGCCCCTCTCACCAG
                 CCCTGTTTCAATGCCATAGGAAGTTTCCATTGTGGATGTCAACCTGGGTATCAGCTCA
                 AAGGCAGAAAATGCATGGATGTGAACGAGTGTAGACAAAATGTATGCAGACCAGATCA
                 GCACTGTAAGAACACCCGTGGTGGCTATAAGTGCATTGATCTTTGTCCAAATGGAATG
                 ACCAAGGCAGAAAATGGAACCTGTATTGATATTGATGAATGTAAAGATGGGACCCATC
                 ACTGCAGATATAACCAGATATGTGAGAATACAAGAGGCAGCTATCGTTGTGTATGCCC
                 AAGAGGTTATCGGTCTCAAGGAGTTGGAAGACCCTGCATGGATATTGATGAATGTGAA
                 AATACAGATGCCTGCCAGCATGAGTGTAAGAATACCTTTGGAAGTTATCAGTGCATCT
                 GCCCACCTGGCTATCAACTCACACACAATGGAAAGACATGCCAAGATATCGATGAATG
                 TCTGGAGCAGAATGTGCACTGTGGACCCAATCGCATGTGCTTCAACATGAGAGGAAGC
                 TACCAGTGCATCGATACACCCTGTCCACCCAACTACCAACGGGATCCTGTTTCAGGGT
                 TCTGCCTCAAGAACTGTCCACCCAATGATTTGGAATGTGCCTTGAGCCCATATGCCTT
                 GGAATACAAACTCGTCTCCCTCCCATTTGGAATAGCCACCAATCAAGATTTAATCCGG
                 CTGGTTGCATACACACAGGATGGAGTGATGCATCCCAGGACAACTTTCCTCATGGTAG
                 ATGAGGAACAGACTGTTCCTTTTGCCTTGAGGGATGAAAACCTGAAAGGAGTGGTGTA
                 TACAACACGACCACTACGAGAAGCAGAGACCTACCGCATGAGGGTCCGAGCCTCATCC
                 TACAGTGCCAATGGGACCATTGAATATCAGACCACATTCATAGTTTATATAGCTGTGT
                 CCGCCTATCCATACTAAGGAACTCTCCAAAGCCTATTCCACATATTTAAACCGCATTA
                 ATCATGGCAATCAAGCCCCCTTCCAGATTACTGTCTCTTGAACAGTTGCAATCTTGGC
                 AGCTTGAAAATGGTGCTACACTCTGTTTTGTGTGCCTTCCTTGGTACTTCTGAGGTAT
                 TTTCATGATCCCACCATGGTCATATCTTGAAGTATCGTCTAGAAAAGTCCCTTATTAT
                 TTTATTTATTACACTGGAGCAGTTACTTCCCAAAGATTATTCTGAACATCTAACAGGA
                 CATATCAGTGATGGTTTACAGTAGTGTAGTACCTAAGATCATTTTCCTGAAAGCCAAA
                 CCAAACAACGAAAAACAAGAACAACTAATTCAGAATCAAATAGAGTTTTTGAGCATTT
                 GACTATTTTTAGAATCATAAAATTAGTTACTAAGTATTTTGATCAAAGCTTATAAAAT
                 AACTTACGGAGATTTTTGTAAGTATTGATACATTATAATAGGACTTGCCTATTTTCAT
                 TTTTAAGAAGAAAAACACCACTCAT
                 ORF Start: ATG at 112 ORF Stop: TAA at 2335
                 SEQ ID NO:84          741 aa MW at 81868.0 kD
NOV25a,          MRRYRTCDNPPPSNGGRACGGPDSQIQRCNTDMCPVDGSWGSWHSWSQCSASCGGGEK
CG93858-01       TRKRLCDHPVPVKGGRPCPGDTTQVTRCNVQACPGGPQRARGSVIGNINDVEFGIAFL
Protein Sequence NATITDSPNSDTRIIRAKITNVPRSLGSAMRKIVSILNPIYWTTAKEIGEAVNGFTLT
                 NAVFKRETQVEFATGEILQMSHIARGLDSDGSLLLDIVVSGYVLQLQSPAEVTVKDYT
                 EDYIQTGPGQLYAYSTRLFTIDGISIPYTWNHTVFYDQAQGRMPFLVETLHASSVESD
                 YNQIEETLGFKIHASISKGDRSNQCPSGFTLDSVGPFCADEDECAAGNPCSHSCHNAM
                 GTYYCSCPKGLTIAADGRTCQDIDECALGRHTCHAGQDCDNTIGSYRCVVRCGSGFRR
                 TSDGLSCQDINECQESSPCHQRCFNAIGSFHCGCEPGYQLKGRKCMDVNECRQNVCRP
                 DQHCKNTRGGYKCIDLCPNGMTKAENGTCIDIDECKDGTHQCRYNQICENTRGSYRCV
                 CPRGYRSQGVGRPCMDIDECENTDACQHECKNTFGSYQCICPPGYQLTHNGKTCQDID
                 ECLEQNVHCGPNRMCFNMRGSYQCIDTPCPPNYQRDPVSGFCLKNCPPNDLECALSPY
                 ALEYKLVSLPFGIATNQDLIRLVAYTQDGVMHPRTTFLMVDEEQTVPFALRDENLKGV
                 VYTTRPLREAETYRMRVRASSYSANGTIEYQTTFIVYIAVSAYPY
                 SEQ ID NO:85          8243 bp
NOV25b,          GCAGAGTACAGTGGTTGGATTTATATTTAGTAAATGGGAATATATGTTGATAACACCT
CG93858-02 DNA   GCTTTCACTTTTAATATATTTACTATTATAGTTCCTCCAAGTGTCATTGGTCCTAAAT
Sequence         CTGAAAATCTTACCGTCGTGGTGAACAATTTCATCTCTTTGACCTGTGAGGTCTCTGG
                 TTTTCCACCTCCTGACCTCAGCTGGCTCAAGAATGAACAGCCCATCAAACTGAACACA
                 AATACTCTCATTGTGCCTGGTGGTCGAACTCTACAGATTATTCGGGCCAAGGTATCAG
                 ATGGTGGTGAATACACTTGTATAGCTATCAATCAAGCTGGCGAAAGCAAGAAAAAGTT
                 TTCCCTGACTGTTTATGTGCCCCCAAGCATTAAAGACCATGACACTGAATCTCTTTCT
                 GTAGTTAATGTAAGAGAGGGAACTTCTGTGTCTTTGGAGTGTGAGTCGAACGCTGTCC
                 CACCTCCAGTCATCACTTGGTATAAGAATGGGCGGATGATAACAGAGTCTACTCATGT
                 GGAGATTTTAGCTGATGGACAAATGCTACACATTAAGAAAGCTGAGGTATCTGACACA
                 GGCCAGTATGTATGTAGAGCTATAAATGTAGCAGGACGGGATGATAAAAATTTCCACC
                 TCAATGTATATGTGCCACCCAGTATTGAAGCACCTGAAAGAGAAGTGATTGTGGAGAC
                 GATCAGCAATCCTGTGACATTAACATGTGATGCCACTGGGATCCCACCTCCCACGATA
                 GCATGGTTAAAGAACCACAAGCGCATAGAAAATTCTGACTCACTGGAAGTTCGTATTT
                 TGTCTGGAGGTAGCAAACTCCAGATTGCCCGGTCTCAGCATTCAGATAGTGGAAACTA
                 TACATGTATTGCTTCAAATATGGAGGGAAAAGCCCAGAAATATTACTTTCTTTCAATT
                 CAAGTTCCTCCAAGTGTTGCTCGTGCTGAAATTCCAAGTGATGTCAGTGTCCTTCTAG
                 GACAAAATGTTGAGCTGGTCTGCAATGCAAATGGCATTCCTACTCCACTTATTCAATG
                 GCTTAAAGATGGAAAGCCCATAGCTAGTGGTGAAACAGAAAGAATCCGAGTGAGTGCA
                 AATGGCAGCACATTAAACATTTATGGAGCTCTTACATCTGACACGGGGAAATACACAT
                 GTGTTGCTACTAATCCCGCTGGAGAAGAAGACCGAATTTTTAACTTGAATGTCTATGT
                 TACACCTACAATTAGGGGTAATAAAGATGAACCAGAGAAACTAATGACTTTAGTGGAT
                 ACTTCAATAAATATTGAATGCAGAGCCACAGGGACGCCTCCACCACAGATAAACTGGC
                 TGAAGAATGGACTTCCTCTGCCTCTCTCCTCCCATATCCGGTTACTGGCAGCAGGACA
                 AGTTATCAGGATTGTGAGAGCTCAGGTGTCTGATGTCGCTGTGTATACTTGTGTGGCC
                 TCCAACAGAGCTGGGGTGGATAATAAGCATTACAATCTTCAAGTGTTTGCACCACCAA
                 ATATGGACAATTCAATGGGGACAGAGGAAATCACAGTTCTCAAAGGTAGTTCCACCTC
                 TATGGCATGCATTACTGATGGAACCCCAGCTCCCAGTATGGCCTGGCTTAGAGATGGC
                 CAGCCTCTGGGGCTTGATGCCCATCTGACAGTCAGCACCCATGGAATGGTCCTGCAGC
                 TCCTCAAAGCAGAGACTGAAGATTCGGGAAAGTACACCTGCATTGCCTCAAATGAAGC
                 TGGAGAAGTCAGCAAGCACTTTATCCTCAAGGTCCTAGAACCACCTCACATTAATGGA
                 TCTGAAGAACATGAAGAGATATCAGTAATTGTTAATAACCCACTTGAACTTACCTGCA
                 TTGCTTCTGGAATCCCAGCCCCTAAAATGACCTGGATGAAAGATGGCCGGCCCCTTCC
                 ACAGACGGATCAAGTGCAAACTCTAGGAGGAGGAGAGGTTCTTCGAATTTCTACTGCT
                 CAGGTGGAGGATACAOGAAGATATACATGTCTGGCATCCAGTCCTGCAGGAGATGATG
                 ATAAGGAATATCTAGTGAGAGTGCATGTACCTCCTAATATTGCTGGAACTGATGAGCC
                 CCGGGATATCACTGTGTTACGGAACAGACAAGTGACATTGGAATGCAAGTCAGATGCA
                 GTGCCCCCACCTGTAATTACTTGGCTCAGAAATGGAGAACGGTTACAGGCAACACCTC
                 GAGTGCGAATCCTATCTGGAGGGAGATACTTGCAAATCAACAATGCTGACCTAGGTGA
                 TACAGCCAATTATACCTGTGTTGCCAGCAACATTGCAGGAAAGACTACAAGAGAATTT
                 ATTCTCACTGTAAATGTTCCTCCAAACATAAAGGGGGGCCCCCAGAGCCTTGTAATTC
                 TTTTAAATAAGTCAACTGTATTGGAATGCATCGCTGAAGGTGTCCCAACTCCAAGGAT
                 AACATGGAGAAAGGATGGAGCTGTTCTAGCTGGGAATCATGCAAGATATTCCATCTTG
                 GAAAATGGATTCCTTCATATTCAATCAGCACATGTCACTGACACTGGACGGTATTTGT
                 GTATGGCCACCAATGCTGCTGGAACAGATCGCAGGCGAATAGATTTACAGGTCCATGT
                 TCCTCCATCTATTGCTCCGGGTCCTACCAACATGACTGTAATAGTAAATGTTCAAACT
                 ACTCTGGCTTGTGAGGCTACTGGGATACCAAAACCATCAATCAATTGGAGAAAAAATG
                 GGCATCTTCTTAATGTGGATCAAAATCAGAACTCATACAGGCTCCTTTCTTCAGGTTC
                 ACTAGTAATTATTTCCCCTTCTGTGGATGACACTGCAACCTATGAATGTACTGTGACA
                 AACGGTGCTGGAGATGATAAAAGAACTGTGGATCTCACTGTCCAAGTTCCACCTTCCA
                 TAGCTGATGAGCCTACAGATTTCCTAGTAACCAAACATGCCCCAGCAGTAATTACCTG
                 CACTGCTTCGGGAGTTCCATTTCCCTCAATTCACTGGACCAAAAATGGTATAAGACTG
                 CTTCCCAGGGGAGATGGCTATAGAATTCTGTCCTCAGGAGCAATTGAAATACTTGCCA
                 CCCAATTAAACCATGCTGGAAGATACACTTGTGTCGCTAGGAATGCGGCTGGCTCTGC
                 ACATCGACACGTGACCCTTCATGTTCATGAGCCTCCAGTCATTCAGCCCCAACCAAGT
                 GAACTACACGTCATTCTGAACAATCCTATTTTATTACCATGTGAAGCAACAGGGACAC
                 CCAGTCCTTTCATTACTTGGCAAAAAGAAGGCATCAATGTTAACACTTCAGGCAGAAA
                 CCATGCAGTTCTTCCTAGTGGCGGCTTACAGATCTCCACACCTCTCCGAGAGGATGCT
                 GGCACTTACATGTGTGTGGCCCAGAACCCGGCTGCTACAGCCTTGGGCAAAATCAAGT
                 TAAATGTCCAAGTTCCTCCAGTCATTAGCCCTCATCTAAAGGAATATGTTATTGCTGT
                 GGACAAGCCCATCACGTTATCCTGTGAAGCAGATGGCCTCCCTCCGCCTGACATTACA
                 TGGCATAAAGATGCGCGTGCAATTGTGGAATCTATCCGCCAGCGCGTCCTCAGCTCTG
                 GCTCTCTGCAAATAACATTTGTCCAGCCTGGTGATGCTGGCCATTACACGTGCATGGC
                 AGCCAATGTAGCAGGATCAAGCAGCACAAGCACCAAGCTCACCGTCCATGTACCACCC
                 AGGATCAGAAGTACAGAAGGACACTACACGGTCAATGAGAATTCACAAGCCATTCTTC
                 CATGCGTAGCTGATGGAATCCCCACACCAGCAATTAACTGGAAAAAAGACAATGTTCT
                 TTTAGCTAACTTGTTAGGAAAATACACTGCTGAACCATATGGAGAACTCATTTTAGAA
                 AATGTTGTGCTGGAGGATTCTGGCTTCTATACCTGTGTTGCTAACAATGCTGCAGGTG
                 AAGATACACACACTGTCAGCCTGACTGTGCATGTTCTCCCCACTTTTACTGAACTTCC
                 TGGAGACGTGTCATTAAATAAAGGAGAACAGCTACGATTAAGCTGTAAAGCTACTGGT
                 ATTCCATTGCCCAAATTAACATGGACCTTCAATAACAATATTATTCCAGCCCACTTTG
                 ACAGTGTGAATGGACACAGTGAACTTGTTATTGAAAGAGTGTCAAAAGAGGATTCAGG
                 TACTTATGTGTGCACCGCAGAGAACAGCGTTGGCTTTGTGAAGGCAATTGGATTTGTG
                 TATGTGAAAGAACCTCCAGTCTTCAAAGGTGATTATCCTTCTCACTGGATTGAACCAC
                 TTGGTGGGAATGCAATCCTGAATTGTGAGGTGAAAGGAGACCCCACCCCAACCATCCA
                 GTGGAACAGAAAGGGAGTGGATATTGAAATTAGCCACAGAATCCGGCAACTGGGCAAT
                 GGCTCCCTGGCCATCTATGGCACTGTTAATGAAGATGCCGGTGACTATACATGTGTAG
                 CTACCAATGAAGCTGGGGTGGTGGAGCGCAGCATGAGTCTGACTCTGCAAAGTCCTCC
                 TATTATCACTCTTGAGCCAGTGGAAACTGTTATTAATGCTGGTGGCAAAATCATATTG
                 AATTGTCAGGCAACTGGAGAGCCTCAACCAACCATTACATGGTCCCGTCAAGGGCACT
                 CTATTTCCTGGGATGACCGGGTTAACGTGTTGTCCAACAACTCATTATATATTGCTGA
                 TGCTCAGAAAGAAGATACCTCTGAATTTGAATGTGTTGCTCGAAACTTAATGGGTTCT
                 GTCCTTGTCAGAGTGCCAGTCATAGTCCAGGTTCATGGTGGATTTTCCCAGTGGTCTG
                 CATGGAGAGCCTGCAGTGTCACCTGTGGAAAAGGCATCCAAAAGAGGAGTCGTCTGTG
                 CAACCAGCCCCTTCCAGCCAATGGTGGGAAGCCCTGCCAAGGTTCAGATTTGGAAATG
                 CGAAACTGTCAAAATAAGCCTTGTCCAGTGGATGGTAGCTGGTCGGAATGGAGTCTTT
                 GGGAAGAATGCACAAGGAGCTGTGGACGCGGCAACCAAACCAGGACCAGGACTTGCAA
                 TAATCCATCAGTTCAGCATGGTGGGCGGCCATGTGAAGGGAATGCTGTGGAAATAATT
                 ATGTGCAACATTACGCCTTGCCCAGTTCATGGAGCATGGAGCGCTTGGCAGCCTTGGG
                 GAACATGCAGCGAAAGTTGTGGGAAAGGTACTCAGACAAGAGCAAGACTTTGTAATAA
                 CCCACCACCAGCGTTTGGTGGGTCCTACTGTGATGGAGCAGAAACACAGATGCAAGTT
                 TGCAATGAAAGAAATTGTCCAGTTCATGGCAAGTGGGCGACTTGGGCCAGTTGGAGTG
                 CCTGTTCTGTGTCATGTGGAGGAGGTGCCACACAGAGAACAAGGCGCTGCTCCGACCC
                 TGTGCCCCAGTATGGAGGAAGGAAATGCGAAGGGAGTGATGTCCAGAGTGATTTTTGC
                 AACAGTGACCCTTGCCCAACCCATGGTAACTGGAGTCCTTGGAGTGGCTGGGGAACAT
                 GCAGCCGGACGTGTAACGGAGGGCAGATGCGGCGGTACCGCACATGTGATAACCCTCC
                 TCCCTCCAATGGGGGAAGAGCTTGTGGGGGACCAGACTCCCAGATCCAGAGGTGCAAC
                 ACTGACATGTGTCCTGTGGATGGAAGTTGGGGAAGCTGGCATAGTTGGAGCCAGTGCT
                 CTGCCTCCTGTGGAGGAGGTGAAAAGACTCGGAAGCGGCTGTGCGACCATCCTGTGCC
                 AGTTAAAGGTGGCCGTCCCTGTCCCGGAGACACTACTCAGGTGACCAGGTGCAATGTA
                 CAAGCATGTCCAGGTGGGCCCCAGCGAGCCAGAGGAAGTGTTATTGGAAATATTAATG
                 ATGTTGAATTTGGAATTGCTTTCCTTAATGCCACAATAACTGATAGCCCTAACTCTGA
                 TACTAGAATAATACGTGCCAAAATTACCAATGTACCTCGTAGTCTTGGTTCAGCAATG
                 AGAAAGATAGTTTCTATTCTAAATCCCATTTATTGGACAACAGCAAAGGAAATAGGAG
                 AAGCAGTCAATGGCTTTACCCTCACCAATGCAGTCTTCAAAAGAGAAACTCAAGTGGA
                 ATTTGCAACTGGAGAAATCTTGCAGATGAGTCATATTGCCCGGGGCTTGGATTCCGAT
                 GGTTCTTTGCTGCTAGATATCGTTGTGAGTGGCTATGTCCTACAGCTTCAGTCACCTG
                 CTGAAGTCACTGTAAAGGATTACACAGAGGACTACATTCAAACAGGTCCTGGGCAGCT
                 GTACGCCTACTCAACCCGGCTGTTCACCATTGATGGCATCAGCATCCCATACACATGG
                 AACCACACCGTTTTCTATGATCAGGCACAGGGAAGAATGCCTTTCTTGGTTGAAACAC
                 TTCATGCATCCTCTGTGGAATCTGACTATAACCAGATAGAAGAGACACTGGGTTTTAA
                 AATTCATGCTTCAATATCCAAAGGAGATCGCAGTAATCAGTGCCCCTCCGGGTTTACC
                 TTAGACTCAGTTGGACCTTTTTGTGCTGATGAGGATGAATGTGCAGCAGGGAATCCCT
                 GCTCCCATAGCTGCCACAATGCCATGGGGACTTACTACTGCTCCTGCCCTAAAGGCCT
                 CACCATAGCTGCAGATGGAAGAACTTGTCAAGATATTGATGAGTGTGCTTTGGGTAGG
                 CATACCTGCCACGCTGGTCAGGACTGTGACAATACGATTGGATCTTATCGCTGTGTGG
                 TCCGTTGTGGAAGTGGCTTTCGAAGAACCTCTGATGGGCTGAGTTGTCAAGATATTAA
                 TGAATGTCAAGAATCCAGCCCCTGTCACCAGCGCTGTTTCAATGCCATAGGAAGTTTC
                 CATTGTGGATGTGAACCTGGGTATCAGCTCAAAGGCAGAAAATGCATGGATGTGAACG
                 AGTGTAGACAAAATGTATGCAGACCAGATCAGCACTGTAAGAACACCCGTGGTGGCTA
                 TAAGTGCATTGATCTTTGTCCAAATGGAATGACCAAGGCAGAAAATGGAACCTGTATT
                 GATATTGATGAATGTAAAGATGGGACCCATCAGTGCAGATATAACCAGATATGTGAGA
                 ATACAAGAGGCAGCTATCGTTGTGTATGCCCAAGAGGTTATCGGTCTCAAGGAGTTGG
                 AAGACCCTGCATGGATATTGATGAATGTGAAAATACAGATGCCTGCCAGCATGAGTGT
                 AAGAATACCTTTGGAAGTTATCAGTGCATCTGCCCACCTGGCTATCAACTCACACACA
                 ATGGAAAGACATGCCAAGATATCGATGAATGTCTGGAGCAGAATGTGCACTGTGGACC
                 CAATCGCATGTGCTTCAACATGAGAGGAAGCTACCAGTGCATCGATACACCCTGTCCA
                 CCCAACTACCAACGGGATCCTGTTTCAGGGTTCTGCCTCAAGAACTGTCCACCCAATG
                 ATTTGGAATGTGCCTTGAGCCCATATGCCTTGGAATACAAACTCGTCTCCCTCCCATT
                 TGGAATAGCCACCAATCAAGATTTAATCCGGCTGGTTGCATACACACAGGATGGAGTG
                 ATGCATCCCAGGACAACTTTCCTCATCGTAGATGAGGAACAGACTGTTCCTTTTGCCT
                 TGAGGGATGAAAACCTGAAAGGAGTGGTGTATACAACACGACCACTACGAGAAGCAGA
                 GACCTACCGCATGAGGGTCCGAGCCTCATCCTACAGTGCCAATGGGACCATTGAATAT
                 CAGACCACATTCATAGTTTATATAGCTGTGTCCGCCTATCCATACTAAGGAACTCTCC
                 AAAGCCTATTCCACATATTTAAACCGCATTAATCATGGCAATCAAGCCCCCTTCCAGA
                 TTACTGTCTCTTGAACAGTTGCAATCTTGGCAGCTTGAAAATGGTGCTACACTCTGTT
                 TTGTGTGCCTTCCTTGGTACTTCTGAGGTATTTTCATGATCCCACCATGGTCATATCT
                 TGAAGTATGGTCTAGAAAAGTCCCTTATTATTTTATTTATTACACTGGAGCAGTTACT
                 TCCCAAAGATTATTCTGAACATCTAACAGGACATATCAGTGATGGTTTACAGTAGTGT
                 AGTACCTAAGATCATTTTCCTGAAAGCCAAACCAAACAACGAAAAACAAGAACAACTA
                 ATTCAGAATCAAATAGAGTTTTTGAGCATTTGACTATTTTTAGAATCATAAAATTAGT
                 TACTAAGTATTTTGATCAAAGCTTATAAAATAACTTACGGAGAATTTTGTAAGTATTG
                 ATACATT
                 ORF Start: ATG at 44  ORF Stop: TAA at 7760
                 SEQ ID NO:86          2572 aa MW at 279540.0 kD
NOV25b,          MLITPAFTFNIFTIIVPPSVIGPKSENLTVVVNNFISLTCEVSGFPPPDLSWLKNEQP
CG93858-02       IKLNTNTLIVPGGRTLQIIRAKVSDGGEYTCIAINQAGESKKKFSLTVYVPPSIKDHD
Protein Sequence SESLSVVNVREGTSVSLECESNAVPPPVITWYKNGRMITESTRVEILADGQMLHI KKA
                 EVSDTGQYVCRAINVAGRDDKNFHLNVYVPPSIEGPEREVIVETISNPVTLTCDATGI
                 PPPTIAWLKNHKRIENSDSLEVRILSGGSKLQIARSQHSDSGNYTCIASNMEGKAQKY
                 YFLSIQVPPSVAGAEIPSDVSVLLGENVELVCNANGIPTPLIQWLKDGKPIASGETER
                 IRVSANGSTLNIYCALTSDTGKYTCVATNPAGEEDRIFNLNVYVTPTIRGNKDEAEKL
                 MTLVDTSINIECRATGTPPPQINWLKNGLPLPLSSHIRLLAAGQVIRIVRAQVSDVAV
                 YTCVASNRAGVDNKHYNLQVFAPPNMDNSMGTEEITVLKGSSTSMACITDGTPAPSMA
                 WLRDGQPLGLDAHLTVSTHGMVLQLLKAETEDSGKYTCIASNEAGEVSKHFILKVLEP
                 PHINGSEEHEEISVIVNNPLELTCIASGIPAPKMTWMKDGRPLPQTDQVQTLGGGEVL
                 RISTAQVEDTGRYTCLASSPAGDDDKEYLVRVHVPPNIAGTDEPRDITVLRNRQVTLE
                 CKSDAVPPPVITWLRNGERLQATPRVRILSGGRYLQINNADLGDTANYTCVASNIAGK
                 TTREFILTVNVPPNIKGGPQSLVILLNKSTVLECIAEGVPTPRITWRKDGAVLAGNHA
                 RYSILENGFLHIQSAHVTDTGRYLCMATNAAGTDRRRIDLQVHLVPPSIAPGPTNMTVI
                 VNVQTTLACEATGIPKPSINWRKNGHLLNVDQNQNSYRLLSSGSLVIISPSVDDTATY
                 ECTVTNGAGDDKRTVDLTVQVPPSIADEPTDFLVTKHAPAVITCTASGVPFPSIHWTK
                 NGIRLLPRGDGYRILSSGAIEILATQLNHAGRYTCVARNAAGSAHRHVTLHVHEPPVI
                 QPQPSELHVILNNPILLPCEATGTPSPFITWQKEGINVNTSGRNHAVLPSGGLQISRA
                 VREDAGTYMCVAQNPAGTALGKIKLNVQVPPVISPHLKEYVIAVDKPITLSCEADGLP
                 PPDITWHKDGRAIVESIRQRVLSSGSLQITFVQPGDAGHYTCMAANVAGSSSTSTKLT
                 VHVPPRIRSTEGHYTVNENSQAILPCVADGIPTPAINWKKDNVLLANLLGKYTAEPYG
                 ELILENVVLEDSGFYTCVANNAAGEDTHTVSLTVHVLPTFTELPGDVSLNKGEQLRLS
                 CKATGIPLPKLTWTFNNNIIPAHFDSVNGHSELVIERVSKEDSGTYVCTAENSVGFVK
                 AIGFVYVKEPPVFKGDYPSHWIEPLGGNAILNCEVKGDPTPTIQWNRKGVDIEISHRI
                 RQLGNGSLAIYGTVNEDAGDYTCVATNEAGVVERSMSLTLQSPPIITLEPVETVINAG
                 GKIILNCQATGEPQPTITWSRQGHSISWDDRVNVLSNNSLYIADAQKEDTSEFECVAR
                 NLMGSVLVRVPVIVQVHGGFSQWSAWRACSVTCGKGIQKRSRLCNQPLPANGGKPCQG
                 SDLEMRNCQNKPCPVDGSWSEWSLWEECTRSCGRGNQTRTRTCNNPSVQHGGRPCEGN
                 AVEIIMCNIRPCPVHGAWSAWQPWCTCSESCGKCTQTRARLCNNPPPAFGGSYCDCAE
                 TQMQVCNERNCPVHGKWATWASWSACSVSCGGGARQRTRGCSDPVPQYGGRKCEGSDV
                 QSDFCNSDPCPTHGNWSPWSGWGTCSRTCNGGQMRRYRTCDNPPPSNGGRACGGPDSQ
                 IQRCNTDMCPVDGSWGSWHSWSQCSASCGGGEKTRKRLCDHPVPVKGGRPCPGDTTQV
                 TRCNVQACPGGPQRARGSVICNINDVEFGIAFLNATITDSPNSDTRIIRAKITNVPRS
                 LGSANRKIVSILNPIYWTTAKEIGEAVNGFTLTNAVFKRETQVEFATGEILQMSHIAR
                 GLDSDGSLLLDIVVSGYVLQLQSPAEVTVKDYTEDYIQTGPGQLYAYSTRLFTIDGIS
                 IPYTWNHTVFYDQAQGRMPFLVETLHASSVESDYNQIEETLGFKIHASISKGDRSNQC
                 PSGFTLDSVGPFCADEDECAAGNPCSHSCHNAMGTYYCSCPKGLTIAADGRTCQDIDE
                 CALGRHTCHAGQDCDNTIGSYRCVVRCGSGFRRTSDGLSCQDINECQESSPCHQRCFN
                 AIGSFHCGCEPGYQLKGRKCMDVNECRQNVCRPDQHCKNTRGGYKCIDLCPNGMTKAE
                 NGTCIDIDECKDGTHQCRYNQICENTRGSYRCVCPRGYRSQGVGRPCMDIDECENTDA
                 CQHECKNTFGSYQCICPPGYQLTHNGKTCQDIDECLEQNVHCGPNRMCFNMRGSYQCI
                 DTPCPPNYQRDPVSGFCLKNCPPNDLECALSPYALEYKLVSLPFGIATNQDLIRLVAY
                 TQDGVMHPRTTFLMVDEEQTVPFALRDENLKGVVYTTRPLREAETYRMRVRASSYSAN
                 GTIEYQTTFIVYIAVSAYPY
                 SEQ ID NO:87          6343 bp
NOV25c,          AACCACCTCACATTAATGGATCTGAAGAACATGAAGAGATATCAGTAATTGTTAATAA
CG56914-03 DNA   CCCACTTGAACTTACCTGCATTGCTTCTGGAATCCCAGCCCCTAAAATGACCTGGATG
Sequence         AAAGATGGCCGGCCCCTTCCACAGACGGATCAAGTGCAAACTCTAGGAGGAGGAGAGG
                 TTCTTCGAATTTCTACTGCTCAGGTGGAGGATACAGGAAGATATACATGTCTGGCATC
                 CAGTCCTGCAGGAGATGATGATAAGGAATATCTAGTGAGAGTGCATGTACCTCCTAAT
                 ATTGCTGGAACTGATGAGCCCCGGGATATCACTGTGTTACGGAACAGACAAGTGACAT
                 TGGAATGCAAGTCAGATGCAGTGCCCCCACCTGTAATTACTTGGCTCAGAAATGGAGA
                 ACGGTTACAGGCAACACCTCGAGTGCGAATCCTATCTGGAGGGAGATACTTGCAAATC
                 AACAATGCTGACCTAGGTGATACAGCCAATTATACCTGTGTTGCCAGCAACATTGCAG
                 GAAAGACTACAAGAGAATTTATTCTCACTGTAAATGTTCCTCCAAACATAAAGGGGGG
                 CCCCCAGAGCCTTGTAATTCTTTTAAATAAGTCAACTGTATTGGAATGCATCGCTGAA
                 GGTGTGCCAACTCCAAGGATAACATGGAGAAAGGATGGAGCTGTTCTAGCTGGGAATC
                 ATGCAAGATATTCCATCTTGGAAAATGGATTCCTTCATATTCAATCAGCACATGTCAC
                 TGACACTGGACGGTATTTGTGTATGGCCACCAATGCTGCTGGAACAGATCGCAGGCGA
                 ATAGATTTACAGGTCCATGGTTCACTACTAATTATTTCCCCTTCTGTGGATGACACTG
                 CAACCTATGAATGTACTGTGACAAACGGTGCTGGAGATGATAAAAGAACTGTGGATCT
                 CACTGTCCAAGTTCCACCTTCCATAGCTGATGAGCCTACAGATTTCCTAGTAACCAAA
                 CATGCCCCAGCAGTAATTACCTGCACTGCTTCGGGAGTTCCATTTCCCTCAATTCACT
                 GGACCAAAAATGGTATAAGACTGCTTCCCAGGGGAGATGGCTATAGAATTCTGTCCTC
                 AGGAGCAATTGAAATACTTGCCACCCAATTAAACCATGCTGGAAGATACACTTGTGTC
                 GCTAGGAATGCGGCTGGCTCTGCACATCGACACGTGACCCTTCATGTTCATGAGCCTC
                 CAGTCATTCAGCCCCAACCAAGTGAACTACACGTCATTCTGAACAATCCTATTTTATT
                 ACCATGTGAAGCAACAGGGACACCCAGTCCTTTCATTACTTGGCAAAAAGAAGGCATC
                 AATGTTAACACTTCAGGCAGAAACCATGCAGTTCTTCCTAGTGGCGGCTTACAGATCT
                 CCAGAGCTGTCCGAGAGGATGCTGGCACTTACATGTGTGTGGCCCAGAACCCGGCTGG
                 TACAGCCTTGGGCAAAATCAAGTTAAATGTCCAAGTTCCTCCAGTCATTAGCCCTCAT
                 CTAAAGGAATATGTTATTGCTGTGGACAAGCCCATCACGTTATCCTGTGAAGCAGATG
                 GCCTCCCTCCGCCTGACATTACATGGCATAAAGATGGGCGTGCAATTGTGGAATCTAT
                 CCGCCAGCGCGTCCTCAGCTCTGGCTCTCTGCAAATAGCATTTGTCCAGCCTGGTGAT
                 GCTGGCCATTACACGTGCATGGCAGCCAATGTAGCAGGATCAAGCAGCACAAGCACCA
                 AGCTCACCGTCCATGTACCACCCAGGATCAGAAGTACAGAAGGACACTACACGGTCAA
                 TGAGAATTCACAAGCCATTCTTCCATGCGTAGCTGATGGAATCCCCACACCAGCAATT
                 AACTGGAAAAAAGACAATGTTCTTTTAGCTAACTTGTTAGGAAAATACACTGCTGAAC
                 CATATGGAGAACTCATTTTAGAAAATGTTGTGCTGGAGGATTCTGGCTTCTATACCTG
                 TGTTGCTAACAATGCTGCAGGTGAAGATACACACACTGTCAGCCTGACTGTGCATGTT
                 CTCCCCACTTTTACTGAACTTCCTGGACACGTGTCATTAAATAAAGGAGAACAGCTAC
                 GATTAAGCTGTAAAGCTACTGGTATTCCATTCCCCAAATTAACATGGACCTTCAATAA
                 CAATATTATTCCAGCCCACTTTGACAGTGTGAATGGACACAGTGAACTTGTTATTGAA
                 AGAGTGTCAAAAGAGGATTCAGGTACTTATGTGTGCACCGCAGAGAACAGCGTTGGCT
                 TTGTGAAGGCAATTGGATTTGTTTATGTGAAAGAACCTCCACTCTTCAAAGGTGATTA
                 TCCTTCTAACTGGATTGAACCACTTGGTGGGAATGCAATCCTGAATTGTGAGGTGAAA
                 GGAGACCCCACCCCAACCATCCAGTGGAACAGAAAGGGAGTGGATATTGAAATTAGCC
                 ACAGAATCCGGCAACTGGGCAATGGCTCCCTGGCCATCTATGGCACTGTTAATGAAGA
                 TGCCGGTGACTATACATGTGTAGCTACCAATGAAGCTGGGGTGGTGGAGCGCAGCATG
                 AGTCTGACTCTGCAAAGTCCTCCTATTATCACTCTTGAGCCAGTGGAAACTGTTATTA
                 ATGCTGGTGGCAAAATCATATTGAATTGTCAGGCAACTGGAGAGCCTCAACCAACCAT
                 TACATGGTCCCGTCAAGGGCACTCTATTTCCTGGGATGACCGGGTTAACGTGTTGTCC
                 AACAACTCATTATATATTGCTGATGCTCAGAAAGAAGATACCTCTGAATTTGAATGCG
                 TTGCTCGAAACTTAATGGGTTCTGTCCTTGTCAGAGTCCCAGTCATAGTCCAGGTTCA
                 TGGTGGATTTTCCCAGTGGTCTGCATGGAGAGCCTGCAGTGTCACCTGTGGAAAAGGC
                 ATCCAAAAGAGGAGTCGTCTGTGCAACCAGCCCCTTCCAGCCAATGGTGGGAAGCCCT
                 GCCAAGGTTCAGATTTGGAAATGCGAAACTGTCAAAATAAGCCTTGTCCAGTGGATGG
                 TAGCTGGTCGGAATGGAGTCTTTGGGAAGAATGCACAAGGAGCTGTGGACGCGGCAAC
                 CAAACCAGGACCAGGACTTGCAATAATCCATCAGTTCAGCATGGTGGGCGGCCATGTG
                 AAGGGAATGCTGTGGAAATAATTATGTGCAACATTAGGCCTTGCCCAGTTCATGGAGC
                 ATGGAGCGCTTGGCAGCCTTGGGGAACATGCAGCGAAAGTTGTGGGAAAGGTACTCAG
                 ACAAGAGCAAGACTTTGTAATAACCCACCACCAGCGTTTGGTGGGTCCTACTGTGATG
                 GAGCAGAAACACAGATGCAAGTTTGCAATGAAAGAAATTGTCCAATTCATGGCAAGTG
                 GGCGACTTGGGCCAGTTGGAGTGCCTGTTCTGTGTCATGTGGAGGAGGTGCCAGACAG
                 AGAACAAGGCGCTGCTCCGACCCTGTGCCCCAGTATGGAGGAAGGAAATGCGAAGGGA
                 GTGATGTCCAGAGTGATTTTTGCAACAGTGACCCTTGCCCAACCCATGGTAACTGGAG
                 TCCTTGGAGTGGCTGGGGAACATGCAGCCGGACGTGTAACGGAGGGCAGATGCGGCGG
                 TACCGCACATGTGATAACCCTCCTCCCTCCAATGGGGGAAGAGCTTGTGGGGGACCAG
                 ACTCCCAGATCCAGAGGTGCAACACTGACATGTGTCCTGTGGATGGAAGTTGGGGAAG
                 CTGGCATAGTTGGAGCCAGTGCTCTGCCTCCTGTGGAGGAGGTGAAAAGACTCGGAAG
                 CGGCTGTGCGACCATCCTGTGCCAGTTAAAGGTGGCCGTCCTTGTCCCGGAGACACTA
                 CTCAGGTGACCAGGTGCAATGTACAAGCATGTCCAGGTGGGCCCCAGCGAGCCAGAGG
                 AAGTGTTATTGGAAATATTAATGATGTTGAATTTGGAATTGCTTTCCTTAATGCCACA
                 ATAACTGATAGCCCTAACTCTGATACTAGAATAATACGTGCCAAAATTACCAATGTAC
                 CTCGTAGTCTTGGTTCAGCAATGAGAAAGATAGTTTCTATTCTAAATCCCATTTATTG
                 GACAACAGCAAAGGAAATAGGAGAAGCAGTCAATGGCTTTACCCTCACCAATGCAGTC
                 TTCAAAAGAGAAACTCAAGTGGAATTTGCAACTGGAGAAATCTTGCAGATGAGTCATA
                 TTGCCCGGGGCTTGGATTCCGATGGTTCTTTGCTGCTAGATATCGTTGTGAGTGGCTA
                 TGTCCTACAGCTTCAGTCACCTGCTGAAGTCACTGTAAAGGATTACACAGAGGACTAC
                 ATTCAAACAGGTCCTGGGCACCTGTACGCCTACTCAACCCGGCTGTTCACCATTGATG
                 GCATCAGCATCCCATACACATGGAACCACACCGTTTTCTATGATCAGGCACAGGGAAG
                 AATGCCTTTCTTGGTTGAAACACTTCATGCATCCTCTGTGGAATCTGACTATAACCAG
                 ATAGAAGAGACACTGGGTTTTAAAATTCATGCTTCAATATCCAAAGGAGATCGCAGTA
                 ATCAGTGCCCCTCCCGGTTTACCTTAGACTCAGTTGGACCTTTTTGTGCTGATGAGGA
                 TGAATGTGCAGCAGGGAATCCCTGCTCCCATAGCTGCCACAATGCCATGGGGACTTAC
                 TACTGCTCCTGCCCTAAAGGCCTCACCATAGCTGCAGATGGAAGAACTTGTCAAGATA
                 TTGATGAGTGTGCTTTGGGTAGGCATACCTGCCACGCTGGTCAGGACTGTGACAATAC
                 GATTGGATCTTATCGCTGTGTGGTCCGTTGTGGAAGTGGCTTTCGAAGAACCTCTGAT
                 GGGCTGAGTTGTCAAGATATTAATGAATGTCAAGAATCCAGCCCCTGTCACCAGCGCT
                 GTTTCAATGCCATAGGAAGTTTCCATTGTGGATGTGAACCTGGGTATCAGCTCAAAGG
                 CAGAAAATGCATGGATGTGAACGAGTGTAGACAAAATGTATGCAGACCAGATCAGCAC
                 TGTAAGAACACCCGTGGTGGCTATAAGTGCATTGATCTTTGTCCAAATGGAATGACCA
                 AGGCAGAAAATGGAACCTGTATTGATATTGATGAATGTAAAGATGGGACCCATCAGTG
                 CAGATATAACCAGATATGTGAGAATACAAGAGGCAGCTATCGTTGTGTATGCCCAAGA
                 GGTTATCGGTCTCAAGGAGTTGGAAGACCCTGCATGGATATTGATGAATGTGAAAATA
                 CAGATGCCTGCCTGCATGAGTGTAAGAATACCTTTGGAAGTTATCAGTGCATCTGCCC
                 ACCTGGCTATCAACTCACACACAATGGAAAGACATGCCAAGATATCGATGAATGTCTG
                 GAGCAGAATGTGCACTGTGGACCCAATCGCATGTGCTTCAACATGAGAGGAAGCTACC
                 AGTGCATCGATACACCCTGTCCACCCAACTACCAACGGGATCCTGCTTCAGGGTTCTG
                 CCTCAAGAACTGTCCACCCAATGATTTGGAATGTGCCTTGAGCCCATATGCCTTGGAA
                 TACAAACTCGTCTCCCTCCCATTTGGAATAGCCACCAATCAAGATTTAATCCGGCTGG
                 TTGCATACACACAGGATGGAGTGATGCATCCCAGGACAACTTTCCTCATGGTAGATGA
                 GGAACAGACTGTTCCTTTTGCCTTGAGGGATGAAAACCTGAAAGGAGTGGTGTATACA
                 ACACGACCACTACGAGAAGCAGAGACCTACCGCATGAGGGTCCGAGCCTCATCCTACA
                 GTGCCAATGGGACCATTGAATATCAGACCACATTCATAGTTTATATAGCTGTGTCCGC
                 CTATCCATACTAAGGAACTCTCCAAAGCCTATTCCACATATTTAAACCGCATTAATCA
                 TGGCAATCAAGCCCCCTTCCAGATTACTGTCTCTTGAACAGTTGCAATCTTGGCAGCT
                 TGAAAATGGTGCTACACTCTGTTTTGTGTGCCTTCCTTGGTACTTCTGAGGTATTTTC
                 ATGATCCCACCATGGTCATATCTTGAAGTATGGTCTAGAAAAGTCCCTTATTATTTTA
                 TTTATTACACTGGAGCAGTTACTTCCCAAAGATTATTCTGAACATCTAACAGGACATA
                 TCAGTGATGGTTTACAGTAGTGTAGTACCTAAGATCATTTTCCTGAAAGCCAAACCAA
                 ACAACGAAAAACAAGAACAACTAATTCAGAATCAAATAGAGTTTTTGAGCATTTGACT
                 ATTTTTAGAATCATAAAATTAGTTACTAAGTATTTTGATCAAAGCTTATAAAATAACT
                 TACGGAGATTTTTGTAAGTATTGATACATTATAATAGGACTTGCCTATTTTCATTTTT
                 AAGAAGAAAAACACCACTCAT
                 ORF Start: ATG at 105 ORF Stop: TAA at 5811
                 SEQ ID NO:88          1902 aa MW at 207163.2 kD
NOV25c,          MTWMKDGRPLPQTDQVQTLGGGEVLRISTAQVEDTGRYTCLASSPAGDDDKEYLVRVH
CG56914-03       VPPNIAGTDEPRDITVLRNRQVTLECKSDAVPPPVITWLRNGERLQATPRVRILSGGR
Protein Sequence YLQINNADLGDTANYTCVASNIAGKTTREFILTVNVPPNIKGGPQSLVILLNKSTVLE
                 CIAEGVPTPRITWRKDGAVLAGNHARYSILENGFLHIQSAHVTDTGRYLCMATNAAGT
                 DRRRIDLQVIIGSLVIISPSVDDTATYECTVTNGAGDDKRTVDLTVQVPPSIADEPTDF
                 LVTKHAPAVITCTASGVPFPSIHWTKNGIRLLPRGDGYRILSSGAIEILATQLNHAGR
                 YTCVARNAAGSAHRHVTLHVHEPPVIQPQPSELHVILNNPILLPCEATGTPSPFITWQ
                 KEGINVNTSGRNHAVLPSGGLQISRAVREDAGTYMCVAQNPAGTALGKIKLNVQVPPV
                 ISPHLKEYVIAVDKPITLSCEADGLPPPDITWRKDGRAIVESIRQRVLSSGSLQIAFV
                 QPGDAGHYTCMAANVAGSSSTSTKLTVHVPPRIRSTEGXYTVNENSQAILPCVADGIP
                 TPAINWKKDNVLLANLLGKYTAEPYGELILENVVLEDSGFYTCVANNAAGEDTHTVSL
                 TVHVLPTFTELPGDVSLNKGEQLRLSCKATGIPLPKLTWTFNNNIIPAHFDSVNGHSE
                 LVIERVSKEDSGTYVCTAENSVGFVKAIGFVYVKEPPVFKGDYPSNWIEPLGGNAILN
                 CEVKGDPTPTIQWNRKGVDIEISHRIRQLGNGSLAIYGTVNEDAGDYTCVATNEAGVV
                 ERSMSLTLQSPPIITLEPVETVINAGGKIILNCQATGEPQPTITWSRQGHSISWDDRV
                 NVLSNNSLYIADAQKEDTSEFECVARNLMGSVLVRVPVIVQVHGGFSQWSAWRACSVT
                 CGKGIQKRSRLCNQPLPANGGKPCQGSDLEMRNCQNKPCPVDGSWSEWSLWEECTRSC
                 GRGNQTRTRTCNNPSVQHGGRPCEGNAVEIIMCNIRPCPVHGAWSAWQPWGTCSESCG
                 KGTQTRARLCNNPPPAFGGSYCDGAETQMQVCNERNCPIHGKWATWASWSACSVSCGG
                 GARQRTRGCSDPVPQYGGRKCEGSDVQSDFCNSDPCPTHGNWSPWSGWGTCSRTCNGG
                 QMRRYRTCDNPPPSNGGRACGGPDSQIQRCNTDMCPVDGSWGSWHSWSQCSASCGGGE
                 KTRKRLCDHPVPVKGGRPCPGDTTQVTRCNVQACPGGPQRARGSVIGNINDVEFGIAF
                 LNATITDSPNSDTRIIRAKITNVPRSLGSAMRKIVSILNPIYWTTAKEIGEAVNGFTL
                 TNAVFKRETQVEFATGEILQMSHIARGLDSDGSLLLDIVVSGYVLQLQSPAEVTVKDY
                 TEDYIQTGPGQLYAYSTRLFTIDGISIPYTWNHTVFYDQAQGRMPFLVETLHASSVES
                 DYNQIEETLGFKIHASISKGDRSNQCPSGFTLDSVGPFCADEDECAAGNPCSHSCHNA
                 MGTYYCSCPKGLTIAADGRTCQDIDECALGRHTCHAGQDCDNTIGSYRCVVRCGSGFR
                 RTSDGLSCQDINECQESSPCHQRCFNAIGSFHCGCEPGYQLKGRKCMDVNECRQNVCR
                 PDQHCKNTRGGYKCIDLCPNGMTKAENGTCIDIDECKDGTHQCRYNQICENTRGSYRC
                 VCPRGYRSQGVGRPCMDIDECENTDACLHECKNTFGSYQCICPPGYQLTHNGKTCQDI
                 DECLEQNVHCGPNRMCFNMRGSYQCIDTPCPPNYQRDPASGFCLKNCPPNDLECALSP
                 YALEYKLVSLPFGIATNQDLIRLVAYTQDGVMHPRTTFLMVDEEQTVPFALRDENLKG
                 VVYTTRPLREAETYRMRVRASSYSANGTIEYQTTFIVYIAVSAYPY

[0400] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 25B.

TABLE 25B
Comparison of NOV25a against NOV25b and NOV25c.
		Identities/
	NOV25a Residues/	Similarities for the
Protein Sequence	Match Residues	Matched Region
NOV25b	1 . . . 741	730/741 (98%)
	1832 . . . 2572	730/741 (98%)
NOV25c	1 . . . 741	728/741 (98%)
	1162 . . . 1902	728/741 (98%)

[0401] Further analysis of the NOV25a protein yielded the following properties shown in Table 25C.

TABLE 25C
Protein Sequence Properties NOV25a
PSort     0.6500 probability located in cytoplasm; 0.1000 probability
analysis: located in mitochondrial matrix space; 0.1000 probability
          located in lysosome (lumen); 0.0000 probability located in
          endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence
analysis:

[0402] 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		Match	the Matched	Expect
Identifier	Protein/Organism/Length [Patent #, Date]	Residues	Region	Value
AAB95002	Human protein sequence SEQ ID	1 . . . 741	741/741 (100%)	0.0
	NO:16644 - Homo sapiens, 741 aa.	1 . . . 741	741/741 (100%)
	[EP1074617-A2, 07-FEB-2001]
AAU16959	Human novel secreted protein, SEQ	1 . . . 741	741/741 (100%)	0.0
	ID 200 - Homo sapiens, 877 aa.	137 . . . 877	741/741 (100%)
	[WO200155441-A2, 02-AUG-2001]
AAG67241	Amino acid sequence of human	1 . . . 741	741/741 (100%)	0.0
	thrombospondin 1-like protein -	40 . . . 780	741/741 (100%)
	Homo sapiens, 780 aa.
	[WO200109321-A1, 08-FEB-2001]
AAG67244	Amino acid sequence of murine	1 . . . 741	673/741 (90%)	0.0
	thrombospondin 1-like protein - Mus	328 . . . 1068	707/741 (94%)
	musculus, 1068 aa. [WO200109321-
	A1, 08-FEB-2001]
AAG67243	Amino acid sequence of murine	1 . . . 741	673/741 (90%)	0.0
	thrombospondin 1-like protein - Mus	4 . . . 744	707/741 (94%)
	musculus, 744 aa. [WO200109321-
	A1, 08-FEB-2001]

[0403] 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
Q96K89	CDNA FLJ14438 FIS, CLONE	1 . . . 741	741/741 (100%)	0.0
	HEMBB1000317, WEAKLY	1 . . . 741	741/741 (100%)
	SIMILAR TO FIBULIN-1,
	ISOFORM D PRECURSOR - Homo
	sapiens (Human), 741 aa.
Q96SC3	FIBULIN-6 - Homo sapiens	1 . . . 580	559/581 (96%)	0.0
	(Human), 2673 aa (fragment).	1816 . . . 2396	567/581 (97%)
Q96RW7	HEMICENTIN - Homo sapiens	1 . . . 580	559/581 (96%)	0.0
	(Human), 5636 aa.	4779 . . . 5359	566/581 (97%)
Q95NZ3	F56H11.1B PROTEIN -	311 . . . 741	160/480 (33%)	4e−62
	Caenorhabditis elegans, 689 aa.	223 . . . 689	224/480 (46%)
Q9TZS1	FIBULIN-1D - Caenorhabditis	311 . . . 741	160/480 (33%)	4e−62
	elegans, 589 aa (fragment).	123 . . . 589	224/480 (46%)

[0404] PFam analysis indicates that the NOV25a protein contains the domains shown in Table 25F.

TABLE 25F
Domain Analysis of NOV25a
		Identities/
		Similarities for
	NOV25a Match	the Matched	Expect
Pfam Domain	Region	Region	Value
tsp_1: domain 1 of 1	41 . . . 91	23/54 (43%)	6.7e−13
		39/54 (72%)
EGF: domain 1 of 7	334 . . . 368	16/47 (34%)	8.4e−06
		25/47 (53%)
granulin: domain 1 of 1	355 . . . 370	7/16 (44%)	4.2
		11/16 (69%)
EGF: domain 2 of 7	374 . . . 413	14/48 (29%)	2
		25/48 (52%)
EGF: domain 3 of 7	419 . . . 451	12/47 (26%)	0.0045
		24/47 (51%)
EGF: domain 4 of 7	457 . . . 493	14/47 (30%)	13
		24/47 (51%)
TILa: domain 1 of 1	467 . . . 522	20/62 (32%)	7.7
		32/62 (52%)
Keratin_B2: domain 1 of 1	383 . . . 525	34/191 (18%)	8.7
		70/191 (37%)
EGF: domain 5 of 7	499 . . . 536	14/47 (30%)	0.0013
		28/47 (60%)
EGF: domain 6 of 7	542 . . . 576	17/47 (36%)	1.3c−07
		28/47 (60%)
EGF: domain 7 of 7	582 . . . 622	13/49 (27%)	17
		26/49 (53%)
fn2: domain 1 of 1	611 . . . 622	7/12 (58%)	7.8
		8/12 (67%)
cadherin: domain 1 of 1	643 . . . 735	15/107 (14%)	5.2
		54/107 (50%)

Example 26

[0405] 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:89          2018 bp
NOV26a,          CTCCCCACGGCGCCAGGAGGACGGGCGAGGGCCGGCAGCCCCCTCTCCCGCGCGCGGC
CG93871-01 DNA   GCAGGAGCCGAGCCCAGCCCGGGGGACCCGCCGCCGCCGGTCATGTGGGCCGGACTGC
Sequence         TCCTTCGGGCCGCCTGTGTCGCGCTCCTGCTGCCGGGGGCACCAGCCCGAGGCTACAC
                 CGGGAGGAAGCCGCCCGGGCACTTCGCGGCCGAGAGGCGCCGACTGGGCCCCCACGTC
                 TGCCTCTCTGGGTTTGGGAGTGGCTGCTGCCCTGGCTGGGCGCCCTCTATGGGTGGTG
                 GGCACTGCACCCTGCGTCTCTGCTCCTTCCGCTGTGGGAGTGGCATCTGCATCGCTCC
                 CAATGTCTGCTCCTGCCAGGATGGAGAGCAAGGGGCCACCTGCCCAGAAACCCATGGA
                 CCATGTGGGGAGTACGGCTGTGACCTTACCTGCAACCATGGAGGCTGTCAGGAGGTGG
                 CCCGAGTGTCCCCCGTGGGCTTCTCGATGACGGAGACAGCTGTTGGCATCAGGTGTGA
                 CATTGACGAATGTGTAACCTCCTCCTGCGAGGGCCACTGTGTGAACACAGAAGGTGGG
                 TTTGTGTGCGAGTGTGGGCCGGGCATGCAGCTGTCTGCCGACCGCCACAGCTGCCAAG
                 ACACTGACGAATGCCTAGGGACTCCCTGTCAGCAGAGATGTAAAAACAGCATTGGCAG
                 CTACAAGTGTTCCTGTCGAACTGGCTTCCACCTTCATGGCAACCGCCACTCCTGTGTA
                 GATGTAAACGAGTGTCGGAGGCCATTGGAGAGGCGAGTCTGTCACCATTCCTGCCACA
                 ACACCGTGGGCAGCTTCCTATGCACATGCCGACCTGGCTTCAGGCTCCGAGCTGACCG
                 CGTGTCCTGTGAAGCTTTCCCGAAAGCCGTGCTGGCCCCATCTGCCATCCTGCAACCC
                 CGGCAACACCCGTCCAAGATGCTTCTGTTGCTTCCTGAGGCCGGCCGGCCTGCCCTGT
                 CCCCAGGACATAGCCCTCCTTCTGGGGCTCCAGGGCCCCCAGCCGGAGTCAGGACCAC
                 CCGCCTGCCATCTCCCACCCCACGACTACCCACATCCTCCCCTTCTGCCCCTGTGTGG
                 CTGCTGTCCACCCTGCTGGCCACCCCAGTGCCTACTGCCTCCCTGCTGGGGAACCTCA
                 GACCCCCCTCACTCCTTCAGGGGGAGGTGATGGGGACCCCTTCCTCACCCAGGGGCCC
                 TGAGTCCCCCCGACTGGCAGCAGGGCCCTCTCCCTGCTGGCACCTGGGAGCCATGCAT
                 GAATCAAGGAGTCGCTGGACAGAGCCTGGGTGTTCCCAGTGCTGCTGCGAGGATGGGA
                 AGGTGACCTGTGAAAAGGTGAGGTGTGAAGCTGCTTGTTCCCACCCAATTCCCTCCAG
                 AGATGGTGGGTGCTGCCCATCGTGCACAGGTTGTTTTCACAGTGGTGTCGTCCGAGCT
                 GAAGGGGATGTGTTTTCACCTCCCAATGAGAACTGCACCGTCTGTGTCTGTCTGCCTG
                 GAAACGTGTCGTGCATCTTTCGTGAGTGTCCTTTTGGCCCGTGTGAGACCCCCCATAA
                 AGACAGATGCTATTTCCACGGCCGGTGGTACGCAGACGGGGCTGTGTTCAGTGGGGGT
                 GGTGACGAGTGTACCACCTGTGTTTGCCAGAATGGGGAGGTGGAGTGCTCCTTCATGC
                 CCTGCCCTGAGCTGGCCTGCCCCCGAGAAGAGTGGCGGCTGGGCCCTGGCCAGTGTTG
                 CTTCACCTGCCAGGAGCCCACACCCTCGACAGGTTGCTCTCTTGACGACAACGGGGTT
                 GAGTTTCCGATTGGACAGATCTGGTCGCCTGGTGACCCCTGTAGATGGCTCGGTCAGC
                 TGCAAGAGGACAGACTGTCTGGACTCCTCCCCTCACCCGATCCGGATCCCTGGACAGT
                 GCTGCCCAGACTGTTCAGCAGGTAATCCCCTGCCTCTGCCCCAAGCCCCCAGGGCAGG
                 GCATCTCAGGCATCGGGCTCCTTAAGCCCTATACAGCCTTCATCTC
                 ORF Start: ATG at 101 ORF Stop: TAA at 1937
                 SEQ ID NO:90          612 aa MW at 65156.4 kD
NOV26a,          MWAGLLLRAACVALLLPGAPARGYTGRKPPGHFAAERRRLGPHVCLSGFGSGCCPGWA
CG93871-01       PSMGGGHCTLRLCSFGCGSGICIAPNVCSCQDGEQGATCPETHGPCGEYGCDLTCNHG
Protein Sequence GCQEVARVCPVGFSMTETAVGIRCDIDECVTSSCEGHCVNTEGGFVCECGPGMQLSAD
                 RHSCQDTDECLGTPCQQRCKNSIGSYKCSCRTGFHLHGNRHSCVDVNECRRPLERRVC
                 HHSCHNTVGSFLCTCRPGFRLRADRVSCEAFPKAVLAPSAILQPRQHPSKMLLLLPEA
                 GRPALSPGHSPPSGAPGPPAGVRTTRLPSPTPRLPTSSPSAPVWLLSTLLATPVPTAS
                 LLGNLRPPSLLQGEVMGTPSSPRGPESPRLAAGPSPCWHLGAMHESRSRWTEPGCSQC
                 WCEDGKVTCEKVRCEAACSHPIPSRDGGCCPSCTGCFHSGVVRAEGDVFSPPNENCTV
                 CVCLAGNVSCMFRECPFGPCETPHKDRCYFHGRWYADGAVFSGGGDECTTCVCQNGEV
                 ECSFMPCPELACPREEWRLGPGQCCFTCQEPTPSTGCSLDDNGVEFPIGQIWSPGDPC
                 RWLGELQEDRLCGLLPSPDPDPWTVLPRLFSR

[0406] Further analysis of the NOV26a protein yielded the following properties shown in Table 26B.

TABLE 26B
Protein Sequence Properties NOV26a
PSort     0.5947 probability located in outside; 0.1900 probability
analysis: located in lysosome (lumen); 0.1000 probability located in
          endoplasmic reticulum (membrane);
          0.1000 probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 22 and 23
analysis:

[0407] 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		Match	the Matched	Expect
Identifier	Protein/Organism/Length [Patent #, Date]	Residues	Region	Value
AAB85364	Novel Von	283 . . . 490	201/208 (96%)	e−124
	Willebrand/thrombosporin-like	1 . . . 208	203/208 (96%)
	polypeptide - Homo sapiens, 235 aa.
	[WO200153485-A1, 26-JUL-2001]
AAM99920	Human polypeptide SEQ ID NO 36 -	388 . . . 580	185/201 (92%)	e−120
	Homo sapiens, 272 aa.	5 . . . 205	188/201 (93%)
	[WO200155173-A2, 02-AUG-2001]
AAM99933	Human polypeptide SEQ ID NO 49 -	388 . . . 580	181/201 (90%)	e−117
	Homo sapiens, 212 aa.	5 . . . 205	185/201 (91%)
	[WO200155173-A2, 02-AUG-2001]
AAB85365	Novel Von	301 . . . 490	183/190 (96%)	c−113
	Willebrand/thrombosporin-like	1 . . . 190	185/190 (97%)
	mature protein sequence - Homo
	sapiens, 217 aa. [WO200153485-A1,
	26-JUL-2001]
ABG15393	Novel human diagnostic protein	70 . . . 138	69/69 (100%)	7e−39
	#15384 - Homo sapiens, 1028 aa.	959 . . . 1027	69/69 (100%)
	[WO200175067-A2, 11-OCT-2001]

[0408] 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
Q96DN2	CDNA FLJ32009 FIS, CLONE	1 . . . 580	570/589 (96%)	0.0
	NT2RP7009498, WEAKLY	1 . . . 589	573/589 (96%)
	SIMILAR TO FIBULIN-1, ISOFORM
	A PRECURSOR - Homo sapiens
	(Human), 955 aa.
Q9DBE2	1300015B04RIK PROTEIN - Mus	1 . . . 606	507/615 (82%)	0.0
	musculus (Mouse), 608 aa.	1 . . . 607	538/615 (87%)
O00274	C1QR(P) - Homo sapiens (Human),	80 . . . 375	104/300 (34%)	5e−32
	652 aa.	300 . . . 566	134/300 (44%)
Q9NPY3	DJ737E23.1 (COMPLEMENT	80 . . . 375	104/300 (34%)	7e−32
	COMPONENT C1Q RECEPTOR) -	300 . . . 566	134/300 (44%)
	Homo sapiens (Human), 652 aa.
Q91V88	POEM (NEPHRONECTIN SHORT	44 . . . 372	103/363 (28%)	5e−31
	ISOFORM) - Mus musculus (Mouse),	35 . . . 383	152/363 (41%)
	561 aa.

[0409] PFam analysis indicates that the NOV26a protein contains the domains shown in Table 26E.

TABLE 26E
Domain Analysis of NOV26a
		Identities/
	NOV26a	Similarities
	Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
EGF: domain 1 of 5	71 . . . 97	9/47	(19%)	8.1
		16/47	(34%)
zf-NF-X1: domain 1 of 1	104 . . . 127	8/27	(30%)	8
		13/27	(48%)
EGF: domain 2 of 5	109 . . . 140	10/47	(21%)	25
		24/47	(51%)
EGF: domain 3 of 5	145 . . . 178	16/47	(34%)	0.0045
		23/47	(49%)
EGF: domain 4 of 5	184 . . . 217	12/47	(26%)	0.011
		25/47	(53%)
TIL: domain 1 of 1	165 . . . 223	13/70	(19%)	0.53
		40/70	(57%)
EGF: domain 5 of 5	223 . . . 260	12/48	(25%)	0.034
		26/48	(54%)
Keratin_B2: domain 1 of 1	93 . . . 271	39/213	(18%)	6.2
		89/213	(42%)
TILa: domain 1 of 1	384 . . . 438	15/59	(25%)	9.4
		28/59	(47%)
vwc: domain 1 of 3	385 . . . 439	21/84	(25%)	7.8e−08
		40/84	(48%)
vwc: domain 2 of 3	442 . . . 492	18/84	(21%)	0.00017
		39/84	(46%)
vwc: domain 3 of 3	493 . . . 550	21/84	(25%)	1.8e−07
		40/84	(48%)

Example 27

[0410] 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:91         2173 bp
NOV27a,          CTGAGGGCTCATCCCTCTGCAGAGCGCGGGGTCACCGGGAGGAGACGCCATGACGCCC
CG93884-01 DNA   GCCCTCACAGCCCTGCTCTGCCTTGGGCTGAGTCTGGGCCCCAGGACCCGCGTGCAGG
Sequence         CAGGGCCCTTCCCCAAACCCACCCTCTGGGCTGAGCCAGGCTCTGTGATCAGCTGGGG
                 GAGCCCCGTGACCATCTGGTGTCAGCGGAGCCTGGAGGCCCAGGAGTACCGACTGGAT
                 AAAGAGGGAAGCCCAGAGCCCTTGCACAGAAATAACCCACTGGAACCCAAGAACAAGG
                 CCAGATTCTCCATCCCATCCATGACAGAGCACCATGCGGGGAGATACCGCTGCCACTA
                 TTACAGCTCTGCAGGCTGGTCAGAGCCCAGCGACCCCCTGGAGCTGGTGATGACAGGA
                 TTCTACAACAAACCCACCCTCTCAGCCCTGCCCAGCCCTGTGGTGGCCTCAGGGGGGA
                 ATATGACCCTCCGATGTGGCTCACAGAAGGGATATCACCATTTTGTTCTGATGAAGGA
                 AGGAGAACACCAGCTCCCCCGGACCCTGGACTCACAGCAGCTCCACAGTGGGGGGTTC
                 CAGGCCCTGTTCCCTGTGGGCCCCGTGAACCCCAGCCACAGGTGGAGGTTCACATGCT
                 ATTACTATTATATGAACACCCCCCAGGTGTGGTCCCACCCCAGTGACCCCCTGGAGAT
                 TCTGCCCTCAGGCGTGTCTAGGAAGCCCTCCCTCCTGACCCTGCAGGGCCCTGTCGTG
                 GCCCCTGGGCAGAGCCTGACCCTCCAGTGTGGCTCTGATGTCGGCTACGACAGATTTG
                 TTCTGTATAAGGAGGGGGAACGTGACTTCCTCCAGCGCCCTGGCCAGCACCCCCAGGC
                 TGGGCTCTCCCAGGCCAACTTCACCCTCGGCCCTGTGAGCCCCTCCCACGGGGGCCAG
                 TACAGGTGCTATGGTGCACACAACCTCTCCTCCGAGTGGTCGGCCCCCAGCGACCCCC
                 TGAACATCCTGATGGCAGGACAGATCTATGACACCGTCTCCCTGTCAGCACAGCCGGC
                 CCCCACAGTGGCCTCAGGAGAGAACGTGACCCTGCTGTGTCAGTCATGGTGGCAGTTT
                 GACACTTTCCTTCTGACCAAAGAAGGGGCAGCCCATCCCCCACTGCGTCTGAGATCAA
                 TGTACGGAGCTCATAAGTACCAGGCTGAATTCCCCATGAGTCCTGTGACCTCAGCCCA
                 CGCGGGGACCTACAGGTGCTACGGCTCATACAGCTCCAACCCCCACCTGCTGTCTTTC
                 CCCAGTGAGCCCCTGGAACTCATGGTCTCAGGACACTCTGGAGGCTCCAGCCTCCCAC
                 CCACAGGGCCGCCCTCCACACCTGGTCTGGGAAGATACCTGGAGGTTTTGATTGGGGT
                 CTCGGTGGCCTTCGTCCTGCTGCTCTTCCTCCTCCTCTTCCTCCTCCTCCGACGTCAG
                 CGTCACAGCAAACACAGGACATCTGACCAGAGAAAGACTGATTTCCAGCGTCCTGCAG
                 GGGCTGCGGAGACAGAGCCCAAGGACAGGGGCCTGCTGAGGAGGTCCAGCCCAGCTGC
                 TGACGTCCAGGAAGAAAACCTCTATGCTGCCGTGAAGGACACACAGTCTGAGGACAGG
                 GTGGAGCTGGACAGTCAGCAGAGCCCACACGATGAAGACCCCCAGGCAGTGACGTATG
                 CCCCGGTGAAACACTCCAGTCCTAGGAGAGAAATGGCCTCTCCTCCCTCCTCACTGTC
                 TGCGGAATTCCTGGACACAAAGGACAGACAGGTGGAAGAGGACAGACAGATGGACACT
                 GAGGCTGCTGCATCTGAAGCCTCCCAGGATGTGACCTACGCCCAGCTGCACAGCTTGA
                 CCCTTAGACGGAAGGCAACTGAGCCTCCTCCATCCCAGGAAGGGCAACCTCCAGCTGA
                 GCCCACCATCTACGCCACTCTGGCCATCCACTAGCCCGGGGGGTACGCAGACCCCACA
                 CTCAGCAGAAGGAGACTCAGGACTGCTGAACGCACGGGAGCTGCCCCCAGTGGACACC
                 AGTGAACCCCAGTCAGCCTGGACCCCTAACACAGACCATGAGGAGACGCTGCGAACTT
                 GTGGGACTCACCTGACTCAGATGACTAATATCGTCCCATTTTGGAAATAAAGCAAC
                 AGACTTCTCAACAATCAATGAGTTAAT
                 ORF Start: ATG at 50 ORF Stop: TAG at 1946
                 SEQ ID NO:92         632 aa MW at 69499.3 kD
NOV27a,          MTPALTALLCLGLSLGPRTRVQAGPFPKPTLWAEPGSVISWGSPVTIWCQGSLEAQEY
CG93884-01       RLDKEGSPEPLDRNNPLEPKNKARFSIPSMTEHHAGRYRCHYYSSAGWSEPSDPLELV
Protein Sequence MTGFYNKPTLSALPSPVVASGGNMTLRCGSQKGYHHFVLMKEGEHQLPRTLDSQQLHS
                 GGFQALFPVGPVNPSHRWRFTCYYYYMNTPQVWSHPSDPLEILPSGVSRKPSLLTLQG
                 PVVAPGQSLTLQCGSDVGYDRFVLYKEGERDFLQRPGQQPQAGLSQANFTLGPVSPSH
                 GGQYRCYGAHNLSSEWSAPSDPLNILMAGQIYDTVSLSAQPGPTVASGENVTLLCQSW
                 WQFDTFLLTKEGAAHPPLRLRSMYGAHKYQAEFPMSPVTSAHAGTYRCYGSYSSNPHL
                 LSFPSEPLELMVSGHSGGSSLPPTGPPSTPGLGRYLEVLIGVSVAFVLLLFLLLFLLL
                 RRQRHSKHRTSDQRKTDFQRPAGAAETEPKDRGLLRRSSPAADVQEENLYAAVKDTQS
                 EDRVELDSQQSPHDEDPQAVTYAPVKHSSPRREMASPPSSLSGEFLDTKDRQVEEDRQ
                 MDTEAAASEASQDVTYAQLHSLTLRRKATEPPPSQEGEPPAEPSIYATLAIH

[0411] Further analysis of the NOV27a protein yielded the following properties shown in Table 27B.

TABLE 27B
Protein Sequence Properties NOV27a
PSort     0.4600 probability located in plasma membrane; 0.1000
analysis: probability located in
          endoplasmic reticulum (membrane);
          0.1000 probability located in endoplasmic
          reticulum (lumen); 0.1000 probability located in outside
SignalP   Cleavage site between residues 24 and 25
analysis:

[0412] 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
AAB61263	Human monocyte inhibitory receptor	1 . . . 632	629/632 (99%)	0.0
	precursor - Homo sapiens, 631 aa.	1 . . . 631	630/632 (99%)
	[WO200100810-A1, 04-JAN-2001]
AAB04177	Leukocyte immunoglobulin like	1 . . . 632	615/632 (97%)	0.0
	receptor pbm 17 - Homo sapiens,	1 . . . 631	623/632 (98%)
	631 aa. [WO200068383-A2,
	16-NOV-2000]
AAW82552	Human LIR-pbm 17 protein - Homo	1 . . . 632	615/632 (97%)	0.0
	sapiens, 631 aa. [WO9848017-A1,	1 . . . 631	623/632 (98%)
	29-OCT-1998]
ABG11435	Novel human diagnostic protein	1 . . . 632	603/641 (94%)	0.0
	#11426 - Homo sapiens, 656 aa.	16 . . . 656	615/641 (95%)
	[WO200175067-A2, 11-OCT-2001]
ABG11435	Novel human diagnostic protein	1 . . . 632	603/641 (94%)	0.0
	#11426 - Homo sapiens, 656 aa.	16 . . . 656	615/641 (95%)
	[WO200175067-A2, 11-OCT-2001]

[0413] 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
O15471	MONOCYTE INHIBITORY	1 . . . 632	630/632 (99%)	0.0
	RECEPTOR PRECURSOR - Homo	1 . . . 631	631/632 (99%)
	sapiens (Human), 631 aa.
AAC51900	IMMUNOGLOBULIN-LIKE	1 . . . 632	629/632 (99%)	0.0
	TRANSCRIPT 5 - Homo sapiens	1 . . . 631	631/632 (99%)
	(Human), 631 aa.
AAC51887	IMMUNOGLOBULIN-LIKE	1 . . . 632	628/632 (99%)	0.0
	TRANSCRIPT 5 PROTEIN - Homo	1 . . . 631	629/632 (99%)
	sapiens (Human), 631 aa.
AAC51901	IMMUNOGLOBULIN-LIKE	1 . . . 632	623/632 (98%)	0.0
	TRANSCRIPT 5 - Homo sapiens	1 . . . 632	628/632 (98%)
	(Human), 632 aa.
AAC51896	IMMUNOGLOBULIN-LIKE	1 . . . 632	620/632 (98%)	0.0
	TRANSCRIPT 5 PROTEIN - Homo	1 . . . 632	626/632 (98%)
	sapiens (Human), 632 aa.

[0414] PFam analysis indicates that the NOV27a protein contains the domains shown in Table 27E.

TABLE 27E
Domain Analysis of NOV27a
		Identities/
		Similarities
	NOV27a	for the
Pfam Domain	Match Region	Matched Region	Expect Value
ig: domain 1 of 4	42 . . . 100	12/63 (19%)	0.00012
		44/63 (70%)
ig: domain 2 of 4	137 . . . 198	9/66 (14%)	1.1e+02
		41/66 (62%)
ig: domain 3 of 4	238 . . . 298	12/65 (18%)	7.7e−07
		47/65 (72%)
ig: domain 4 of 4	338 . . . 398	13/65 (20%)	0.0043
		39/65 (60%)

Example B

Identification of NOVX Clones

[0415] The novel NOVX target sequences identified in the present invention may have been 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, and uterus.

[0416] 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.

Example C

Quantitative Expression Analysis of Clones in Various Cells and Tissues

[0417] 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 diseases), Panel CNSD.01 (containing central nervous system samples from normal and diseased brains) and CNS_neurodegeneration_panel (containing samples from normal and Alzheimer's diseased brains).

[0418] 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.

[0419] 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.

[0420] 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 1X TaqMan® Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer's instructions.

[0421] 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.

[0422] 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.

[0423] 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 1X 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

[0424] 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.

[0425] In the results for Panels 1, 1.1, 1.2 and 1.31), the following abbreviations are used:

[0426] ca.=carcinoma,

[0427] *=established from metastasis,

[0428] met=metastasis,

[0429] s cell var=small cell variant,

[0430] non-s=non-sm=non-small,

[0431] squam=squamous,

[0432] pl. eff=pl effusion=pleural effusion,

[0433] glio=glioma,

[0434] astro=astrocytoma, and

[0435] neuro=neuroblastoma.

General_screening_panel_v1.4

[0436] The plates for Panel 1.4 include 2 control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in Panel 1.4 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 Panel 1.4 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 Panel 1.4 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 and 2.2

[0437] The plates for Panels 2D and 2.2 generally include 2 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). 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 or CHTN). 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.

Panel 3D

[0438] The plates of Panel 3D 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.

Panels 4D, 4R, and 4.1D

[0439] 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.).

[0440] 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/ml, 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.

[0441] 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 μPM 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 2×106cells/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.

[0442] 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.

[0443] 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 106cells/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 CD8 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 (Clyclone), 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.

[0444] 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.

[0445] 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 105-106cells/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 fL-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.

[0446] 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 5×105cells/ml for 8 days, changing the media every 3 days and adjusting the cell concentration to 5×105cells/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 CCD 106 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.

[0447] For these cell lines and blood cells, RNA was prepared by lysing approximately 107cells/ml using Trizol (Gibco BRL). Briefly, 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 RNAs in 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 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

[0448] 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.

[0449] 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.

[0450] 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.

[0451] 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.

[0452] 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-I anti-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.

[0453] In the labels employed to identify tissues in the AI_comprehensive panel_V1.0 panel, the following abbreviations are used:

[0454] AI=Autoimmunity

[0455] Syn=Synovial

[0456] Normal=No apparent disease

[0457] Rep22/Rep2O=individual patients

[0458] RA=Rheumatoid arthritis

[0459] Backus=From Backus Hospital

[0460] OA=Osteoarthritis

[0461] (SS) (BA) (MF)=Individual patients

[0462] Adj=Adjacent tissue

[0463] Match control=adjacent tissues

[0464] M=Male

[0465] F=Female

[0466] COPD=Chronic obstructive pulmonary disease

Panels 5D and 5I

[0467] 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.

[0468] 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:

[0469] Patient 2 Diabetic Hispanic, overweight, not on insulin

[0470] Patient 7-9 Nondiabetic Caucasian and obese (BMI>30)

[0471] Patient 10 Diabetic Hispanic, overweight, on insulin

[0472] Patient 11 Nondiabetic African American and overweight

[0473] Patient 12 Diabetic Hispanic on insulin

[0474] Adipocyte differentiation was induced in donor progenitor cells obtained from Osirus (a division of Clonetics/Bio Whittaker) 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:

[0475] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose

[0476] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated

[0477] Donor 2 and 3 AD: Adipose, Adipose Differentiated

[0478] 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.

[0479] 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.

[0480] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:

[0481] GO Adipose=Greater Omentum Adipose

[0482] SK=Skeletal Muscle

[0483] UT=Uterus

[0484] PL=Placenta

[0485] AD=Adipose Differentiated

[0486] AM=Adipose Midway Differentiated

[0487] U=Undifferentiated Stem Cells

Panel CNSD.01

[0488] 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.

[0489] 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.

[0490] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:

[0491] PSP=Progressive supranuclear palsy

[0492] Sub Nigra=Substantia nigra

[0493] Glob Palladus=Globus palladus

[0494] Temp Pole=Temporal pole

[0495] Cing Gyr=Cingulate gyrus

[0496] BA 4=Brodman Area 4

Panel CNS_Neurodegeneration_V1.0

[0497] 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.

[0498] 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.

[0499] In the labels employed to identify tissues in the CNS_Neurodegeneration_V1.0 panel, the following abbreviations are used:

[0500] AD=Alzheimer's disease brain; patient was demented and showed AD-like

[0501] pathology upon autopsy

[0502] Control=Control brains; patient not demented, showing no neuropathology

[0503] Control (Path)=Control brains; patient not demented but showing sever AD-like pathology

[0504] SupTemporal Ctx=Superior Temporal Cortex

[0505] Inf Temporal Ctx=Inferior Temporal Cortex

[0506] A. NOV1a and NOV1b (CG56258-01 and CG56258-02: Sodium/Calcium Exchanger)

[0507] Expression of gene CG56258-021 and CG56258-02 was assessed using the primer-probe sets Ag2903, Ag5035 and Ag6163, described in Tables AA, AB and AC. Results of the RTQ-PCR runs are shown in Tables AD, AE, AF, AG, AH and AI.

TABLE AA
Probe Name Ag2903
			Start	Seq ID
Primers	Sequences	Length	Position	No:
Forward	5′-gactcgcaagatcaagcatcta-3′	22	641	93
Probe	TET-5′cttcttcatcaccgctgcttggagta-3′-TAMRA	26	668	94
Reverse	5′-tagagccagatgtaggcaaaga-3′	22	694	95

[0508]

TABLE AB
Probe Name Ag5035
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-gaaagccagtattgggtgaac-3′	21	2023	96
Probe	TET-5′-ccccaaactagaagtcatcattgaaga-3′-TAMRA	27	2045	97
Reverse	5′-tttgtccaccgtagtcttgaac-3′	22	2081	98

[0509]

TABLE AC
Probe Name Ag6163
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-ggggagttggaattcaagaat-3′	21	1815	99
Probe	TET-5′-tgaaactgtcaaaacaattcacatcaag-3′-TAMRA	28	1838	100
Reverse	5′-tctcatatgcctcatcatcaattac-3′-	25	1866	101

[0510]

TABLE AD
AI-comprehensive panel-v1.0
	Rel. Exp.(%)	Rel. Exp.(%)		Rel. Exp.(%)	Rel. Exp.(%)
	Ag2903, Run	Ag5035, Run		Ag2903, Run	Ag5035, Run
Tissue Name	225410015	244570389	Tissue Name	225410015	244570389
110967 COPD-F	0.6	0.3	112427 Match	4.1	4.8
			Control
			Psoriasis-F
110980 COPD-F	0.4	0.6	112418	0.8	0.5
			Psoriasis-M
110968 COPD-M	0.9	1.2	112723 Match	0.1	0.0
			Control
			Psoriasis-M
110977 COPD-M	0.9	0.8	112419	1.3	0.9
			Psoriasis-M
110989	0.6	0.0	112424 Match	1.1	0.5
Emphysema-F			Control
			Psoriasis-M
110992	0.4	0.7	112420	2.1	2.2
Emphysema-F			Psoriasis-M
110993	1.1	1.4	112425 Match	2.9	5.8
Emphysema-F			Control
			Psoriasis-M
110994	1.0	0.7	104689 (MF)	68.3	44.4
Emphysema-F			OA Bone-
			Backus
110995	1.1	0.8	104690 (MF)	8.8	5.2
Emphysema-F			Adj “Normal”
			Bone-Backus
110996	0.0	0.0	104691 (MF)	2.1	1.7
Emphysema-F			OA Synovium-
			Backus
110997	1.5	0.6	104692 (BA)	3.3	3.6
Asthma-M			OA Cartilage-
			Backus
111001	1.8	1.5	104694 (BA)	100.0	100.0
Asthma-F			OA Bone-
			Backus
111002	1.9	1.9	104695 (BA)	36.3	28.7
Asthma-F			Adj “Normal”
			Bone-Backus
111003 Atopic	2.7	2.4	104696 (BA)	1.4	0.5
Asthma-F			OA Synovium-
			Backus
111004 Atopic	0.9	1.2	104700 (SS)	54.0	37.6
Asthma-F			OA Bone-
			Backus
111005 Atopic	0.9	1.1	104701 (SS)	60.3	34.9
Asthma-F			Adj “Normal”
			Bone-Backus
111006 Atopic	0.4	0.3	104702 (SS)	2.9	2.1
Asthma-F			OA Synovium-
			Backus
111417	2.2	2.8	117093 OA	1.4	0.4
Allergy-M			Cartilage Rep7
112347	0.6	0.0	112672 OA	4.8	3.3
Allergy-M			Bone5
112349 Normal	0.9	0.0	112673 OA	1.6	1.7
Lung-F			Synovium5
112357 Normal	0.1	0.3	112674 OA	2.6	2.6
Lung-F			Synovial Fluid
			cells5
112354 Normal	0.0	0.3	117100 OA	0.0	0.0
Lung-M			Cartilage
			Rep14
112374	0.2	0.0	112756 OA	5.6	0.4
Crohns-F			Bone9
112389 Match	0.2	1.1	112757 OA	32.3	37.4
Control			Synovium9
Crohns-F
112375	0.0	0.0	112758 OA	1.1	0.6
Crohns-F			Synovial Fluid
			Cells9
112732 Match	0.8	0.8	117125 RA	2.8	1.1
Control			Cartilage Rep2
Crohns-F
112725	0.1	0.0	113492 Bone2	3.0	1.2
Crohns-M			RA
112387 Match	1.6	1.1	113493	1.6	0.8
Control			Synovium2
Crohns-M			RA
112378	0.6	0.0	113494 Syn	1.8	0.8
Crohns-M			Fluid Cells RA
112390 Match	1.0	0.8	113499	1.7	1.9
Control			Cartilage4 RA
Crohns-M
112726	0.8	0.7	113500 Bone4	2.6	2.2
Crohns-M			RA
112731 Match	0.9	0.3	113501	2.0	0.7
Control			Synovium4
Crohns-M			RA
112380 Ulcer	0.4	0.5	113502 Syn	0.6	0.6
Col-F			Fluid Cells4
			RA
112734 Match	3.5	1.8	113495	1.6	0.6
Control Ulcer			Cartilage3 RA
Col-F
112384 Ulcer	2.7	1.9	113496 Bone3	1.9	0.7
Col-F			RA
112737 Match	0.5	0.6	113497	1.4	0.8
Control Ulcer			Synovium3
Col-F			RA
112386 Ulcer	2.0	1.4	113498 Syn	2.6	2.7
Col-F			Fluid Cells3
			RA
112738 Match	0.1	0.3	117106	0.4	0.0
Control Ulcer			Normal
Col-F			Cartilage
			Rep20
112381 Ulcer	1.3	0.0	113663 Bone3	0.6	0.0
Col-M			Normal
112735 Match	3.3	1.2	113664	0.2	0.0
Control Ulcer			Synovium3
Col-M			Normal
112382 Ulcer	1.2	0.6	113665 Syn	0.2	0.0
Col-M			Fluid Cells3
			Normal
112394 Match	0.9	0.8	117107	2.9	0.4
Control Ulcer			Normal
Col-M			Cartilage
			Rep22
112383 Ulcer	0.7	0.0	113667 Bone4	1.1	0.0
Col-M			Normal
112736 Match	0.7	0.3	113668	1.3	0.5
Control Ulcer			Synovium4
Col-M			Normal
112423	0.7	0.3	113669 Syn	1.1	0.5
Psoriasis-F			Fluid Cells4
			Normal

[0511]

TABLE AE
CNS-neurodegeneration-v1.0
	Rel. Exp.(%)	Rel. Exp.(%)		Rel. Exp.(%)	Rel. Exp.(%)
Tissue	Ag2903, Run	Ag5035, Run	Tissue	Ag2903, Run	Ag5035, Run
Name	209735156	224062761	Name	209735156	224062761
AD 1 Hippo	9.1	8.1	Control	3.9	3.2
			(Path) 3
			Temporal
			Ctx
AD 2 Hippo	24.1	35.6	Control	32.8	89.5
			(Path) 4
			Temporal
			Ctx
AD 3 Hippo	8.2	4.5	AD 1	15.4	8.8
			Occipital
			Ctx
AD 4 Hippo	7.7	9.7	AD 2	0.0	0.0
			Occipital
			Ctx
			(Missing)
AD 5 Hippo	100.0	84.1	AD 3	5.5	1.9
			Occipital
			Ctx
AD 6 Hippo	22.2	20.3	AD 4	18.8	16.3
			Occipital
			Ctx
Control 2	31.0	50.3	AD 5	56.6	63.7
Hippo			Occipital
			Ctx
Control 4	9.1	10.7	AD 6	20.6	13.6
Hippo			Occipital
			Ctx
Control	5.5	1.4	Control 1	1.7	2.7
(Path) 3			Occipital
Hippo			Ctx
AD 1	7.7	7.5	Control 2	63.3	76.3
Temporal			Occipitol
Ctx			Ctx
AD 2	21.6	34.4	Control 3	24.7	14.3
Temporal			Occipital
Ctx			Ctx
AD 3	4.8	3.8	Control 4	5.6	5.0
Temporal			Occipital
Ctx			Ctx
AD 4	18.2	24.7	Control	89.5	100.0
Temporal			(Path) 1
Ctx			Occipital
			Ctx
AD 5 Inf	82.9	97.3	Control	15.6	8.8
Temporal			(Path) 2
Ctx			Occipital
			Ctx
AD 5 Sup	32.1	31.4	Control	1.0	0.9
Temporal			(Path) 3
Ctx			Occipital
			Ctx
AD 6 Inf	26.6	21.2	Control	19.2	21.0
Temporal			(Path) 4
Ctx			Occipital
			Ctx
AD 6 Sup	29.5	18.9	Control 1	6.9	5.4
Temporal			Parietal Ctx
Ctx
Control 1	4.2	3.1	Control 2	27.0	26.6
Temporal			Parietal Ctx
Ctx
Control 2	51.1	50.3	Control 3	22.7	12.3
Temporal			Parietal Ctx
Ctx
Control 3	23.8	15.3	Control	100.0	87.7
Temporal			(Path) 1
Ctx			Parietal Ctx
Control 3	6.4	5.6	Control	29.5	19.2
Temporal			(Path) 2
Ctx			Parietal Ctx
Control	68.3	73.7	Control	3.8	1.3
(Path) 1			(Path) 3
Temporal			Parietal Ctx
Ctx
Control	49.7	27.9	Control	61.6	46.0
(Path) 2			(Path) 4
Temporal			Parietal Ctx
Ctx

[0512]

TABLE AF
General-screening-panel-v1.5
	Rel. Exp.(%)	Rel. Exp.(%)		Rel. Exp.(%)	Rel. Exp.(%)
	Ag5035, Run	Ag5035, Run		Ag5035, Run	Ag5035, Run
Tissue Name	228967202	244373096	Tissue Name	228967202	244373096
Adipose	1.6	2.2	Renal ca. TK-10	0.0	0.0
Melanoma*	0.0	0.0	Bladder	0.6	0.3
Hs688(A).T
Melanoma*	0.0	0.0	Gastric ca. (liver	0.0	0.0
Hs688(B).T			met.) NCI-N87
Melanoma*	0.0	0.0	Gastric ca.	0.0	0.0
M14			KATO III
Melanoma*	0.0	0.0	Colon ca. SW-	0.0	0.0
LOXIMVI			948
Melanoma*	0.0	0.0	Colon ca. SW480	0.0	0.0
SK-MEL-5
Squamous	0.0	0.0	Colon ca.*	0.0	0.0
cell			(SW480 met)
carcinoma			SW620
SCC-4
Testis Pool	0.0	0.1	Colon ca. HT29	0.0	0.0
Prostate ca.*	0.0	0.0	Colon ca.	0.0	0.0
(bone met)			HCT-116
PC-3
Prostate Pool	1.4	2.0	Colon ca.	0.2	0.2
			CaCo-2
Placenta	0.3	0.1	Colon cancer	0.7	0.1
			tissue
Uterus Pool	2.1	1.6	Colon ca.	0.0	0.0
			SW1116
Ovarian ca.	0.0	0.0	Colon ca.	0.0	0.0
OVCAR-3			Colo-205
Ovarian ca.	0.0	0.0	Colon ca. SW-48	0.0	0.0
SK-OV-3
Ovarian ca.	0.3	0.0	Colon Pool	3.5	3.1
OVCAR-4
Ovarian ca.	0.0	0.0	Small Intestine	1.1	1.3
OVCAR-5			Pool
Ovarian ca.	0.0	0.0	Stomach Pool	0.2	1.4
IGROV-1
Ovarian ca.	0.0	0.0	Bone Marrow	2.3	1.8
OVCAR-8			Pool
Ovary	0.3	0.3	Fetal Heart	0.3	0.6
Breast ca.	0.0	0.0	Heart Pool	0.8	0.0
MCF-7
Breast ca.	0.0	0.0	Lymph Node	2.6	2.0
MDA-MB-231			Pool
Breast ca. BT	0.0	0.0	Fetal Skeletal	17.9	22.2
549			Muscle
Breast ca.	0.0	0.0	Skeletal Muscle	100.0	83.5
T47D			Pool
Breast ca.	0.0	0.0	Spleen Pool	0.6	0.0
MDA-N
Breast Pool	2.6	3.5	Thymus Pool	0.6	0.4
Trachea	0.8	1.1	CNS cancer	0.0	0.0
			(glio/astro) U87-
			MG
Lung	0.0	0.0	CNS cancer	0.2	0.0
			(glio/astro) U-
			118-MG
Fetal Lung	14.3	14.5	CNS cancer	0.0	0.0
			(neuro; met) SK-
			N-AS
Lung ca. NCI-N417	0.0	0.0	CNS cancer	0.0	0.0
			(astro) SF-539
Lung ca. LX-1	0.0	0.0	CNS cancer	0.0	0.2
			(astro) SNB-75
Lung ca. NCI-H146	0.0	0.0	CNS cancer	0.0	0.0
			(glio) SNB-19
Lung ca.	9.3	12.7	CNS cancer	0.0	0.0
SHP-77			(glio) SF-295
Lung ca.	0.0	0.0	Brain	32.8	31.0
A549			(Amygdala) Pool
Lung ca. NCI-H526	0.2	0.2	Brain	69.7	76.3
			(cerebellum)
Lung ca. NCI-H23	0.0	0.0	Brain (fetal)	90.1	100.0
Lung ca. NCI-H460	0.0	0.0	Brain	27.9	31.0
			(Hippocampus)
			Pool
Lung ca.	0.0	0.0	Cerebral Cortex	36.3	48.3
HOP-62			Pool
Lung ca. NCI-H522	0.0	0.0	Brain (Substantia	31.0	32.1
			nigra) Pool
Liver	0.0	0.0	Brain (Thalamus)	50.0	50.3
			Pool
Fetal Liver	2.1	2.0	Brain (whole)	46.0	38.2
Liver ca.	0.0	2.0	Spinal Cord Pool	17.6	18.4
HepG2
Kidney Pool	1.8	0.0	Adrenal Gland	2.5	2.5
Fetal Kidney	0.8	0.7	Pituitary gland	1.3	1.2
			Pool
Renal ca. 786-0	0.0	0.0	Salivary Gland	0.0	0.2
Renal ca.	0.0	0.0	Thyroid (female)	0.0	0.0
A498
Renal ca.	0.0	0.0	Pancreatic ca.	0.0	0.0
ACHN			CAPAN2
Renal ca. UO-	0.0	0.0	Pancreas Pool	1.6	7.9
31

[0513]

TABLE AG
Panel 1.3D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag2903,		Ag2903,
	Run		Run
Tissue Name	162556420	Tissue Name	162556420
Liver adenocarcinoma	0.0	Kidney (fetal)	0.3
Pancreas	0.0	Renal ca. 786-0	0.0
Pancreatic ca.	0.0	Renal ca. A498	0.0
CAPAN 2
Adrenal gland	0.1	Renal ca. RXF 393	0.0
Thyroid	0.2	Renal ca. ACHN	0.0
Salivary gland	0.1	Renal ca. UO-31	0.1
Pituitary gland	0.4	Renal ca. TK-10	0.0
Brain (fetal)	2.0	Liver	0.0
Brain (whole)	3.9	Liver (fetal)	0.4
Brain (amygdala)	3.7	Liver ca.	0.0
		(hepatoblast) HepG2
Brain (cerebellum)	3.3	Lung	0.0
Brain (hippocampus)	5.6	Lung (fetal)	0.4
Brain	0.9	Lung ca. (small cell)	0.0
(substantia nigra)		LX-1
Brain (thalamus)	5.9	Lung ca. (small cell)	0.2
		NCI-H69
Cerebral Cortex	80.7	Lung ca.	3.4
		(s.cell var.)
		SHP-77
Spinal cord	1.7	Lung ca. (large	0.0
		cell) NCI-H460
glio/astro U87-MG	0.0	Lung ca. (non-sm.	0.1
		cell) A549
glio/astro U-118-MG	0.0	Lung ca.	0.0
		(non-s.cell)
		NCI-H23
astrocytoma SW1783	0.6	Lung ca.	0.0
		(non-s.cell)
		HOP-62
neuro*; met SK-N-AS	0.0	Lung ca. (non-s.cl)	0.0
		NCI-H522
astrocytoma SF-539	0.0	Lung ca. (squam.)	0.0
		SW 900
astrocytoma SNB-75	0.0	Lung ca. (squam.)	0.2
		NCI-H596
glioma SNB-19	0.1	Mammary gland	0.1
glioma U251	0.0	Breast ca.* (pl.ef)	0.0
		MCF-7
glioma SF-295	0.0	Breast ca.* (pl.ef)	0.0
		MDA-MB-231
Heart (fetal)	5.2	Breast ca.* (pl.ef)	0.0
		T47D
Heart	0.3	Breast ca. BT-549	0.0
Skeletal muscle (fetal)	100.0	Breast ca. MDA-N	0.0
Skeletal muscle	21.2	Ovary	0.2
Bone marrow	0.2	Ovarian ca.	0.0
		OVCAR-3
Thymus	0.6	Ovarian ca.	0.3
		OVCAR-4
Spleen	0.0	Ovarian ca.	0.0
		OVCAR-5
Lymph node	0.3	Ovarian ca.	0.0
		OVCAR-8
Colorectal	1.1	Ovarian ca.	0.0
		IGROV-1
Stomach	0.1	Ovarian ca.*	0.0
		(ascites) SK-OV-3
Small intestine	0.2	Uterus	0.1
Colon ca. SW480	0.0	Placenta	0.0
Colon ca.*	0.0	Prostate	0.0
SW620(SW480 met)
Colon ca. HT29	0.0	Prostate ca.* (bone	0.0
		met) PC-3
Colon ca. HCT-116	0.0	Testis	0.3
Colon ca. CaCo-2	0.0	Melanoma	0.0
		Hs688(A).T
Colon ca.	0.5	Melanoma* (met)	0.0
tissue(ODO3866)		Hs688(B).T
Colon ca. HCC-2998	0.0	Melanoma UACC-	0.2
		62
Gastric ca.* (liver met)	0.0	Melanoma M14	0.0
NCI-N87
Bladder	0.2	Melanoma LOX	0.0
		IMVI
Trachea	0.3	Melanoma* (met)	0.0
		SK-MEL-5
Kidney	0.0	Adipose	0.3

[0514]

TABLE AH
Panel 2D
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag2903,		Ag2903,
	Run		Run
Tissue Name	162345106	Tissue Name	162345106
Normal Colon	8.1	Kidney Margin	0.5
		8120608
CC Well to Mod Diff	0.3	Kidney Cancer	0.0
(ODO3866)		8120613
CC Margin	0.3	Kidney Margin	0.1
(ODO3866)		8120614
CC Gr.2 rectosigmoid	0.1	Kidney Cancer	0.5
(ODO3868)		9010320
CC Margin	0.2	Kidney Margin	0.0
(ODO3868)		9010321
CC Mod Diff	0.3	Normal Uterus	1.0
(ODO3920)
CC Margin	0.4	Uterus Cancer	0.5
(ODO3920)		064011
CC Gr.2 ascend colon	1.1	Normal Thyroid	1.0
(ODO3921)
CC Margin	0.9	Thyroid Cancer	0.0
(ODO3921)		064010
CC from Partial	0.4	Thyroid Cancer	0.0
Hepatectomy		A302152
(ODO4309)
Mets
Liver Margin	0.1	Thyroid Margin	0.1
(ODO4309)		A302153
Colon mets to lung	0.1	Normal Breast	3.0
(OD04451-01)
Lung Margin	1.3	Breast Cancer	0.4
(OD04451-02)		(OD04566)
Normal Prostate	2.3	Breast Cancer	0.8
6546-1		(OD04590-01)
Prostate Cancer	1.2	Breast Cancer Mets	1.5
(OD04410)		(OD04590-03)
Prostate Margin	4.2	Breast Cancer	0.2
(OD04410)		Metastasis
		(OD04655-05)
Prostate Cancer	1.2	Breast Cancer	0.5
(OD04720-01)		064006
Prostate Margin	4.6	Breast Cancer 1024	1.2
(OD04720-02)
Normal Lung	5.8	Breast Cancer	1.8
061010		9100266
Lung Met to	0.0	Breast Margin	1.1
Muscle		9100265
(ODO4286)
Muscle Margin	100.0	Breast Cancer	0.6
(ODO4286)		A209073
Lung Malignant	0.8	Breast Margin	0.0
Cancer		A209073
(OD03126)
Lung Margin	7.7	Normal Liver	0.0
(OD03126)
Lung Cancer	1.4	Liver Cancer	0.0
(OD04404)		064003
Lung Margin	4.1	Liver Cancer 1025	0.0
(OD04404)
Lung Cancer	0.3	Liver Cancer 1026	0.0
(OD04565)
Lung Margin	1.2	Liver Cancer	0.1
(OD04565)		6004-T
Lung Cancer	0.7	Liver Tissue 6004-N	0.5
(OD04237-01)
Lung Margin	2.4	Liver Cancer	0.0
(OD04237-02)		6005-T
Ocular Mel Met	0.0	Liver Tissue 6005-N	0.0
to Liver
(ODO4310)
Liver Margin	0.1	Normal Bladder	0.6
(ODO4310)
Melanoma Mets	0.1	Bladder Cancer	0.2
to Lung		1023
(OD04321)
Lung Margin	2.4	Bladder Cancer	1.4
(OD04321)		A302173
Normal Kidney	1.5	Bladder Cancer	0.5
		(OD04718-01)
Kidney Ca, Nuclear	0.5	Bladder Normal	4.9
grade 2		Adjacent
(OD04338)		(OD04718-03)
Kidney Margin	1.4	Normal Ovary	0.1
(OD04338)
Kidney Ca	1.8	Ovarian Cancer	1.9
Nuclear grade		064008
1/2 (OD04339)
Kidney Margin	0.6	Ovarian Cancer	0.0
(OD04339)		(OD04768-07)
Kidney Ca, Clear cell	1.0	Ovary Margin	0.2
type (OD04340)		(OD04768-08)
Kidney Margin	0.8	Normal Stomach	4.5
(OD04340)
Kidney Ca, Nuclear	1.3	Gastric Cancer	1 .7
grade 3 (OD04348)		9060358
Kidney Margin	0.7	Stomach Margin	1.5
(OD04348)		9060359
Kidney Cancer	0.7	Gastric Cancer	1.2
(OD04622-01)		9060395
Kidney Margin	0.0	Stomach Margin	2.0
(OD04622-03)		9060394
Kidney Cancer	0.0	Gastric Cancer	0.6
(OD04450-01)		9060397
Kidney Margin	0.1	Stomach Margin	1.7
(OD04450-03)		9060396
Kidney Cancer	0.1	Gastric Cancer	2.9
8120607		064005

[0515]

TABLE AI
Panel 4.1D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag5035, Run		Ag5035, Run
Tissue Name	223740981	Tissue Name	223740981
Secondary Th1 act	0.0	HUVEC IL-1beta	2.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNFalpha + IFN	1.9
		gamma
Secondary Th1 rest	0.0	HUVEC TNFalpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC	0.0
		none
Primary Th1 act	0.0	Lung Microvascular EC	100.0
		TNFalpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	2.0	Microsvasular Dermal EC	55.5
		TNFalpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	2.2
		TNFalpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	4.2
		none
Primary Tr1 rest	0.0	Small airway epithelium	3.7
		TNFalpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC rest	2.3
lymphocyte act
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 TNFalpha +	0.0
lymphocyte rest		IL-1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	10.6
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	13.6
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNFalpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	8.4	NCI-H292 none	0.0
LAK cells IL-2 + IFN	2.9	NCI-H292 IL-4	0.0
gamma
LAK cells IL-2 + IL-18	3.8	NCI-H292 IL-9	0.0
LAK cells	2.3	NCI-H292 IL-13	2.5
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	2.1	HPAEC none	0.0
Two Way MLR 5 day	2.3	HPAEC	8.8
		TNFalpha + IL-1beta
Two Way MLR 7 day	1.8	Lung fibroblast none	0.0
PBMC rest	6.7	Lung fibroblast	0.0
		TNFalpha + IL-1beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	6.3	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.0
Ramos (B cell)	0.0	Lung fibroblast IFN	0.0
ionomycin		gamma
B lymphocytes PWM	9.2	Dermal fibroblast	0.0
		CCD1070 rest
B lymphocytes CD40L	1.9	Dermal fibroblast	0.0
and IL-4		CCD1070 TNFalpha
EOL-1 dbcAMP	0.0	Dermal fibroblast	0.0
		CCD1070 IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN	0.0
PMA/ionomycin		gamma
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	2.4	Dermal Fibroblasts rest	2.0
Dendritic cells anti-	0.0	Neutrophils TNFa + LPS	0.0
CD40
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	31.6	Colon	5.4
Macrophages rest	1.7	Lung	8.1
Macrophages LPS	6.5	Thymus	5.1
HUVEC none	0.0	Kidney	0.0
HUVEC starved	0.0

[0516] AI_comprehensive panel_v1.0 Summary: Ag2903/Ag5035 Two experiments with two different probe and primer sets produce results that are in very good agreement. Expression of the CG56258-01 gene appears to be more highly associated with synovium and bone samples from patients with osteoarthritis when compared to expression in the control samples. Thus, therapeutic modulation of the expression or function of this gene may be effective in the treatment of osteoarthritis. A third experiment with the probe and primer set Ag6163 shows low/undetectable levels of expression (CTs>35).

[0517] CNS_neurodegeneration_v1.0 Summary: Ag2903/Ag5035 Two experiments with two different probes and primers produce results that are in excellent agreement. This panel does not show differential expression of the CG56258-01 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain, with highest expression in the hippocampus of an Alzheimer's patient and the occipital cortex of a control patient (CTs=28-30). Please see Panel 1.3D for discussion of utility of this gene in the central nervous system.

[0518] General_screening_panel_v1.5 Summary: Ag5035 Two experiments with the same probe and primer produce results that are in excellent agreement, with the CG56258-02 gene showing highly brain preferential expression (CTs=30-31). In addition, moderate levels of expression are seen in fetal and adult skeletal muscle (CTs=30-31). This expression profile is in excellent concordance with the results in Panel 1.3D. Please see Panel 1.3D for further discussion of utility of this gene in the central nervous system and metabolic disease.

[0519] Panel 1.3D Summary: Ag2903 Expression of the CG56258-01 gene is highest in fetal skeletal muscle (CT=26.8). In addition, significant levels of expression are also seen in adult skeletal muscle and fetal heart. Thus, expression of this gene could be used to differentiate skeletal muscle derived samples from other samples on this panel and as a marker of skeletal muscle. This gene encodes a putative sodium/calcium exchanger. Altered levels of intracellular calcium have been implicated in many diseases, including type 2 diabetes. Based on its expression profile and homology to a calcium transport protein, therapeutic modulation of the expression or function of this gene or gene product may be effective in the treatment of type 2 diabetes.

[0520] In addition, moderate to low levels of expression are seen in all regions of the CNS examined. Inhibition of calcium uptake has been shown to decrease neuronal death in response to cerebral ischemia. Therefore, this gene, a putative calcium transport protein, represents an excellent drug target for the treatment of stroke. Treatment with an antagonist immediately after stroke could decrease total infarct volume and lessen the overall stroke severity.

[0521] See, generally,

[0522] Balasubramanyam M, Balaji R A, Subashini B, Mohan V. Evidence for mechanistic alterations of Ca2+ homeostasis in Type 2 diabetes mellitus. Int J Exp Diabetes Res 2001;1(4):275-87. PMID: 11467418; and

[0523] Matsuda T, Arakawa N, Takuma K, Kishida Y, Kawasaki Y, Sakaue M, Takahashi K, Takahashi T, Suzuki T, Ota T, Hamano-Takahashi A, Onishi M, Tanaka Y, Kameo K, Baba A. SEA0400, a novel and selective inhibitor of the Na+−Ca2+ exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic models. J Pharmacol Exp Ther 2001 July;298(1):249-56.

[0524] Panel 2D Summary: Ag2903 The expression of the CG56258-01 gene in this panel is consistent with the profile seen in Panel 1.3D. Expression is highest and most prominent in a normal muscle sample (CT=28.7). Please see Panel 1.3D for discussion of utility of this gene in metabolic disease.

[0525] Panel 4.1D Summary: Ag5035 Expression of the CG56258-02 gene is restricted to TNF-alpha and IL-1 beta treated lung and dermal microvasculature (CTs=33-34). Endothelial cells are known to play important roles in inflammatory responses by altering the expression of surface proteins that are involved in activation and recruitment 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. Therefore, therapeutic modulation of the protein encoded by this gene may lead to amelioration of symptoms associated with psoriasis, asthma, allergies, chronic obstructive pulmonary disease, and emphysema.

[0526] Ag5035 Results from one experiment with this gene are not included. The amp plot indicates that there were experimental difficulties with this run.

[0527] Ag6163 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0528] B. NOV2a (CG59843-01: fibropellin III-like)

[0529] Expression of gene CG59843-01 was assessed using the primer-probe sets Ag2797, Ag3606 and Ag221, described in Tables BA, BB and BE. Results of the RTQ-PCR runs are shown in Tables BD, BE, BF, BG, BH, BI, BJ, BK and BL.

TABLE BA
Probe Name Ag2797
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-cagctacaaatgcctctgtgat-3′	22	1488	102
Probe	TET-5′-ccaggttaccatggcctctactgtga-3′-TAMRA	26	1510	103
Reverse	5′-agcggagaggcactcattatat-3′	22	1542	104

[0530]

TABLE BB
Probe Name Ag3606
			Start	SEQ ID
Primer	Sequences	Length	Position	No:
Forward	5′-cagctacaaatgcctctgtgat-3′	22	1488	105
Probe	TET-5′-ccaggttaccatggcctctactgtga-3′-TAMRA	26	1510	106
Reverse	5′-agcggagaggcactcattatat-3′	22	1542	107

[0531]

TABLE BC
Probe Name Ag221
			Start	SEQ ID
Primers	Sequences	Position	No:
Forward	5′-ctgccaggtaggcagtgtca-3′	20	545	108
Probe	TET-5′-aaaatcctgcctcgctctcaggcaa-3′-TAMRA	25	517	109
Reverse	5′-gcctgttcctgctactcagga-3′	21	489	110

[0532]

TABLE BD
CNS-neurodegeneration-v1.0
	Rel. Exp.(%)	Rel. Exp.(%)		Rel. Exp.(%)	Rel. Exp.(%)
	Ag2797, Run	Ag3606, Run	Tissue	Ag2797, Run	Ag3606, Run
Tissue Name	208699245	210997602	Name	208699245	210997602
AD 1 Hippo	8.0	14.9	Control	2.7	3.4
			(Path) 3
			Temporal
			Ctx
AD 2 Hippo	19.8	40.9	Control	12.0	21.5
			(Path) 4
			Temporal
			Ctx
AD 3 Hippo	7.3	11.1	AD 1	9.5	16.3
			Occipital
			Ctx
AD 4 Hippo	7.0	12.1	AD2	92.7	0.0
			Occipital
			Ctx
			(Missing)
AD 5 hippo	97.3	61.1	AD 3	5.6	0.1
			Occipital
			Ctx
AD 6 Hippo	31.9	88.9	AD 4	15.1	27.0
			Occipital
			Ctx
Control 2	14.6	47.0	AD 5	97.3	25.5
Hippo			Occipital
			Ctx
Control 4	12.4	19.8	AD 6	99.3	57.8
Hippo			Occipital
			Ctx
Control (Path)	5.1	12.3	Control 1	2.6	3.4
3 Hippo			Occipital
			Ctx
AD 1 Temporal	10.7	16.7	Control 2	51.8	73.2
Ctx			Occipital
			Ctx
AD 2 Temporal	19.5	41.8	Control 3	0.2	15.3
Ctx			Occipital
			Ctx
AD 3 Temporal	3.2	6.7	Control 4	6.4	13.1
Ctx			Occipital
			Ctx
AD 4 Temporal	14.7	25.0	Control	63.7	97.3
Ctx			(Path) 1
			Occipital
			Ctx
AD 5 Inf	100.0	100.0	Control	7.9	10.9
Temporal Ctx			(Path) 2
			Occipital
			Ctx
AD 5	100.0	51.4	Control	4.1	2.8
SupTemporal			(Path) 3
Ctx			Occipital
			Ctx
AD 6 Inf	36.1	65.1	Control	4.8	9.7
Temporal Ctx			(Path) 4
			Occipital
			Ctx
AD 6 Sup	26.2	50.0	Control 1	7.3	7.6
Temporal Ctx			Parietal Ctx
Control 1	6.1	6.9	Control 2	95.9	36.6
Temporal Ctx			Parietal Ctx
Control 2	25.2	54.0	Control 3	10.4	19.8
Temporal Ctx			Parietal Ctx
Control 3	6.0	14.9	Control	34.9	70.2
Temporal Ctx			(Path) 1
			Parietal Ctx
Control 4	4.3	8.9	Control	12.9	22.7
Temporal Ctx			(Path) 2
			Parietal Ctx
Control (Path)	33.4	50.3	Control	2.2	3.5
1 Temporal Ctx			(Path) 3
			Parietal Ctx
Control (Path)	12.6	27.0	Control	16.7	28.5
2 Temporal Ctx			(Path) 4
			Parietal Ctx

[0533]

TABLE BE
General_screening_panel_v1.4
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag3606,		Ag3606,
	Run		Run
Tissue Name	217675868	Tissue Name	217675868
Adipose	0.0	Renal ca. TK-10	0.1
Melanoma*	0.1	Bladder	0.1
Hs688(A).T
Melanoma*	2.9	Gastric ca.	0.3
Hs688(B).T		(liver met.)
		NCI-N87
Melanoma* M14	0.0	Gastric ca.	0.0
		KATO III
Melanoma*	10.4	Colon ca. SW-948	0.0
LOXIMVI
Melanoma* SK-	97.9	Colon ca. SW480	0.0
MEL-5
Squamous cell	1.4	Colon ca.* (SW480	0.0
carcinoma SCC-4		met) SW620
Testis Pool	0.4	Colon ca. HT29	0.0
Prostate ca.* (bone	0.1	Colon ca. HCT-116	0.6
met) PC-3
Prostate Pool	0.3	Colon ca. CaCo-2	0.0
Placenta	0.1	Colon cancer tissue	0.3
Uterus Pool	0.3	Colon ca. SW1116	0.0
Ovarian ca.	0.1	Colon ca. Colo-205	0.0
OVCAR-3
Ovarian ca. SK-OV-3	0.2	Colon ca. SW-48	0.0
Ovarian ca.	0.0	Colon Pool	0.2
OVCAR-4
Ovarian ca.	0.7	Small Intestine Pool	0.3
OVCAR-5
Ovarian ca. IGROV-1	1.2	Stomach Pool	0.4
Ovarian ca.	0.6	Bone Marrow Pool	0.2
OVCAR-8
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.2
Breast ca. MDA-	0.7	Lymph Node Pool	0.3
MB-231
Breast ca. BT 549	2.9	Fetal Skeletal	0.0
		Muscle
Breast ca. T47D	1.0	Skeletal Muscle	0.0
		Pool
Breast ca. MDA-N	5.4	Spleen Pool	0.8
Breast Pool	0.2	Thymus Pool	0.1
Trachea	1.3	CNS cancer	100.0
		(glio/astro)
		U87-MG
Lung	0.0	CNS cancer	42.0
		(glio/astro)
		U-118-MG
Fetal Lung	0.4	CNS cancer	0.0
		(neuro;met)
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer	0.3
		(astro) SF-
		539
Lung ca. LX-1	0.0	CNS cancer (astro)	1.2
		SNB-75
Lung ca. NCI-H146	12.0	CNS cancer	1.0
		(glio)
		SNB-19
Lung ca. SHP-77	40.6	CNS cancer	23.7
		(glio) SF-
		295
Lung ca. A549	0.1	Brain (Amygdala)	18.2
		Pool
Lung ca. NCI-H526	0.0	Brain (cerebellum)	77.4
Lung ca. NCI-H23	2.2	Brain (fetal)	32.1
Lung ca. NCI-H460	34.2	Brain	19.2
		(Hippocampus)
		Pool
Lung ca. HOP-62	2.1	Cerebral	20.2
		Cortex Pool
Lung ca. NCI-H522	0.0	Brain	24.7
		(Substantia nigra)
		Pool
Liver	0.0	Brain (Thalamus)	25.5
		Pool
Fetal Liver	0.0	Brain (whole)	26.8
Liver ca. HepG2	0.0	Spinal Cord Pool	24.0
Kidney Pool	1.1	Adrenal Gland	26.4
Fetal Kidney	4.1	Pituitary gland Pool	5.0
Renal ca. 786-0	0.0	Salivary Gland	10.0
Renal ca. A498	0.1	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca.	0.3
		CAPAN2
Renal ca. UO-31	0.3	Pancreas Pool	0.7

[0534]

TABLE BF
Panel 1
	Rel. Exp.(%) Ag221,		Rel. Exp.(%) Ag221,
Tissue Name	Run 87987754	Tissue Name	Run 87987754
Endothelial cells	0.0	Renal ca. 786-0	0.0
Endothelial cells	0.0	Renal ca. A498	0.0
(treated)
Pancreas	0.0	Renal ca. RXF 393	0.0
Pancreatic ca. CAPAN 2	0.0	Renal ca. ACHN	0.0
Adrenal gland	22.8	Renal ca. UO-31	0.0
Thyroid	0.0	Renal ca. TK-10	0.0
Salivary gland	6.7	Liver	0.0
Pituitary gland	0.0	Liver (fetal)	0.0
Brain (fetal)	15.3	Liver ca.	0.0
		(hepatoblast) HepG2
Brain (whole)	42.6	Lung	0.0
Brain (amygdala)	19.9	Lung (fetal)	0.0
Brain (cerebellum)	100.0	Lung ca. (small cell)	0.0
		LX-1
Brain (hippocampus)	17.9	Lung ca. (small cell)	0.0
		NCI-H69
Brain (substantia nigra)	40.9	Lung ca. (s.cell var.)	0.0
		SHP-77
Brain (thalamus)	39.5	Lung ca. (large	0.0
		cell)NCI-H460
Brain (hypothalamus)	7.9	Lung ca. (non-sm.	0.0
		cell) A549
Spinal cord	13.6	Lung ca. (non-s.cell)	0.6
		NCI-H23
glio/astro U87-MG	21.0	Lung ca. (non-s.cell)	0.6
		HOP-62
glio/astro U-118-MG	10.4	Lung ca. (non-s.cl)	0.0
		NCI-H522
astrocytoma SW1783	1.8	Lung ca. (squam.)	0.0
		SW 900
neuro*; met SK-N-AS	0.0	Lung ca. (squam.)	0.0
		NCI-H596
astrocytoma SF-539	0.0	Mammary gland	0.0
astrocytoma SNB-75	0.0	Breast ca.* (pl.ef)	0.0
		MCF-7
glioma SNB-19	0.3	Breast ca.* (pl.ef)	0.0
		MDA-MB-231
glioma U251	0.0	Breast ca.* (pl. ef)	0.0
		T47D
glioma SF-295	3.5	Breast ca. BT-549	0.0
Heart	0.0	Breast ca. MDA-N	2.8
Skeletal muscle	0.0	Ovary	0.0
Bone marrow	0.0	Ovarian ca. OVCAR-3	0.0
Thymus	0.0	Ovarian ca. OVCAR-4	0.0
Spleen	0.0	Ovarian ca. OVCAR-5	0.0
Lymph node	0.0	Ovarian ca. OVCAR-8	0.2
Colon (ascending)	0.2	Ovarian ca. IGROV-1	0.0
Stomach	1.7	Ovarian ca. (ascites)	0.0
		SK-OV-3
Small intestine	0.3	Uterus	1.5
Colon ca. SW480	0.0	Placenta	0.0
Colon ca.* SW620	0.0	Prostate	0.9
(SW480 met)
Colon ca. HT29	0.0	Prostate ca.* (bone	0.0
		met) PC-3
Colon ca. HCT-116	0.0	Testis	0.2
Colon ca. CaCo-2	0.0	Melanoma	0.0
		Hs688(A).T
Colon ca. HCT-15	0.0	Melanoma* (met)	0.2
		Hs688(B).T
Colon ca. HCC-2998	0.0	Melanoma UACC-62	0.0
Gastric ca.* (liver met)	0.0	Melanoma M14	0.0
NCI-N87
Bladder	0.2	Melanoma LOX	1.7
		IMVI
Trachea	3.1	Melanoma* (met)	21.3
		SK-MEL-5
Kidney	1.5	Melanoma SK-MEL-	0.0
Kidney (fetal)	5.9	28

[0535]

TABLE BG
Panel 1.3D
	Rel. Exp.(%)	Rel. Exp.(%)		Rel. Exp.(%)	Rel. Exp.(%)
	Ag2797, Run	Ag2797, Run		Ag2797, Run	Ag2797, Run
Tissue Name	165643064	165693893	Tissue Name	165643064	165693893
Liver	0.5	0.9	Kidney (fetal)	2.1	4.5
adenocarcinoma
Pancreas	0.0	0.0	Renal ca. 786-0	0.0	0.0
Pancreatic ca.	0.3	0.2	Renal ca.	0.5	0.6
CAPAN 2			A498
Adrenal gland	11.7	15.6	Renal ca. RXF	0.1	0.0
			393
Thyroid	0.0	0.1	Renal ca.	0.0	0.0
			ACHN
Salivary gland	6.7	9.3	Renal ca. UO-	3.5	0.4
			31
Pituitary gland	13.7	12.2	Renal ca. TK-	0.1	0.1
			10
Brain (fetal)	27.9	31.2	Liver	0.0	0.0
Brain (whole)	59.0	66.9	Liver (fetal)	0.1	0.0
Brain (amygdala)	33.4	35.4	Liver ca.	0.0	0.1
			(hepatoblast)
			HepG2
Brain (cerebellum)	71.2	82.4	Lung	0.1	0.3
Brain	29.7	37.4	Lung (fetal)	0.1	0.0
(hippocampus)
Brain (substantia	41.8	52.9	Lung ca.	0.0	0.0
nigra)			(small cell)
			LX-1
Brain (thalamus)	100.0	100.0	Lung ca.	0.0	0.0
			(small cell)
			NCI-H69
Cerebral Cortex	26.6	28.7	Lung ca.	14.3	15.3
			(s.cell var.)
			SHP-77
Spinal cord	27.7	38.2	Lung ca.	28.3	29.1
			(large
			cell) NCI-
			H460
glio/astro U87-MG	16.5	21.2	Lung ca. (non-	0.1	0.1
			Sm. cell) A549
glio/astro U-118-	13.8	21.0	Lung ca. (non	0.6	1.0
MG			s.cell) NCI-
			H23
astrocytoma	4.4	4.3	Lung ca. (non-	3.1	1.4
SW1783			s.cell) HOP-62
neuro*; met SK-N-	0.0	0.1	Lung ca. (non-	0.7	0.0
AS			s.cl) NCI-
			H522
astrocytoma SF-	0.1	0.0	Lung ca.	0.1	0.1
539			(squam.) SW
			900
astrocytoma SNB-	0.5	0.3	Lung ca.	0.3	0.1
75			(squam.) NCI-
			H596
glioma SNB-19	1.0	0.6	Mammary	0.3	0.2
			gland
glioma U251	0.8	0.4	Breast ca.*	0.1	0.0
			(pl.ef) MCF-7
glioma SF-295	4.2	4.2	Breast ca.*	0.3	0.5
			(pl.ef) MDA-
			MB-231
Heart (fetal)	0.2	0.2	Breast ca.*	0.0	0.0
			(pl.ef) T47D
Heart	0.3	0.1	Breast ca. BT-	1.3	2.0
			549
Skeletal muscle	0.1	3.5	Breast ca.	0.6	1.2
(fetal)			MDA-N
Skeletal muscle	0.0	0.2	Ovary	0.0	0.1
Bone marrow	0.0	0.0	Ovarian ca.	0.1	0.2
			OVCAR-3
Thymus	0.1	0.1	Ovarian ca.	0.0	0.1
			OVCAR-4
Spleen	1.5	0.8	Ovarian ca.	0.2	0.1
			OVCAR-5
Lymph node	0.2	0.2	Ovarian ca.	0.2	0.2
			OVCAR-8
Colorectal	0.2	0.1	Ovarian ca.	0.1	0.0
			IGROV-1
Stomach	1.9	2.5	Ovarian ca.*	0.1	0.1
			(ascites) SK-
			OV-3
Small intestine	0.8	2.1	Uterus	0.5	1.1
Colon ca. SW480	0.0	0.0	Placenta	0.1	0.1
Colon ca.*	0.0	0.1	Prostate	0.2	0.9
SW620(SW480
met)
Colon ca. HT29	0.0	0.0	Prostate ca.*	0.0	0.0
			(bone met)PC-
			3
Colon ca. HCT-	0.1	0.2	Testis	0.2	0.5
116
Colon ca. CaCo-2	0.0	0.0	Melanoma	0.1	0.1
			Hs688(A).T
Colon ca.	0.1	0.4	Melanoma*	0.2	0.1
tissue(ODO3866)			(met)
			Hs688(B).T
Colon ca. HCC-	0.0	0.0	Melanoma	0.7	0.3
2998			UACC-62
Gastric ca.* (liver	0.5	0.6	Melanoma	0.2	0.1
met) NCI-N87			M14
Bladder	0.0	0.0	Melanoma	0.3	0.3
			LOX IMVI
Trachea	1.0	1.2	Melanoma*	18.6	16.2
			(met) SK-
			MEL-5
Kidney	1.0	1.8	Adipose	0.1	0.1

[0536]

TABLE BH
Panel 2D
	Rel. Exp.(%)	Rel. Exp.(%)		Rel. Exp.(%)	Rel. Exp.(%)
	Ag2797, Run	Ag2797, Run		Ag2797, Run	Ag2797, Run
Tissue Name	163577803	165910585	Tissue Name	163577803	165910585
Normal Colon	24.0	8.5	Kidney	18.3	10.2
			Margin
			8120608
CC Well to Mod	0.4	0.4	Kidney	0.5	100.0
Diff (ODO3866)			Cancer
			8120613
CC Margin	6.3	2.1	Kidney	15.8	8.4
(ODO3866)			Margin
			8120614
CC Gr. 2	0.2	0.2	Kidney	36.6	24.3
rectosigmoid			Cancer
(ODO3868)			9010320
CC Margin	1.8	0.9	Kidney	19.3	14.5
(ODO3868)			Margin
			9010321
CC Mod Diff	0.2	0.0	Normal Uterus	4.2	1.5
(ODO3920)
CC Margin	6.8	5.7	Uterus Cancer	4.9	2.3
(ODO3920)			064011
CC Gr.2 ascend	2.0	0.5	Normal	1.7	0.1
colon			Thyroid
(ODO3921)
CC Margin	2.1	1.2	Thyroid	0.0	0.0
(ODO3921)			Cancer
			064010
CC from Partial	0.0	0.0	Thyroid	0.1	0.0
Hepatectomy			Cancer
(ODO4309)			A302152
Mets
Liver Margin	0.0	0.0	Thyroid	0.0	0.1
(ODO4309)			Margin
			A302153
Colon mets to	1.3	0.1	Normal Breast	3.3	1.5
lung (OD04451-
01)
Lung Margin	10.7	4.5	Breast Cancer	0.0	0.0
(OD04451-02)			(OD04566)
Normal Prostate	98.6	16.2	Breast Cancer	0.0	0.7
6546-1			(OD04590-01)
Prostate Cancer	7.9	2.3	Breast Cancer	1.1	0.0
(OD04410)			Mets
			(OD04590-03)
Prostate Margin	8.4	4.4	Breast Cancer	1.0	0.0
(OD04410)			Metastasis
			(OD04655-05)
Prostate Cancer	3.2	2.6	Breast Cancer	0.4	0.2
(OD04720-01)			064006
Prostate Margin	9.1	3.4	Breast Cancer	5.9	2.7
(OD04720-02)			1024
Normal Lung	15.7	6.5	Breast Cancer	0.1	0.1
061010			9100266
Lung Met to	6.0	2.2	Breast Margin	1.0	0.4
Muscle			9100265
(ODO4286)
Muscle Margin	0.0	0.0	Breast Cancer	47.0	56.6
(ODO4286)			A209073
Lung Malignant	24.0	11.5	Breast Margin	7.0	3.4
Cancer			A209073
(OD03126)
Lung Margin	7.6	1.9	Normal Liver	0.0	0.1
(OD03126)
Lung Cancer	0.5	0.4	Liver Cancer	0.0	0.0
(OD04404)			064003
Lung Margin	4.8	2.8	Liver Cancer	0.0	0.0
(OD04404)			1025
Lung Cancer	2.0	0.5	Liver Cancer	0.0	0.0
(OD04565)			1026
Lung Margin	1.9	1.2	Liver Cancer	0.1	0.0
(OD04565)			6004-T
Lung Cancer	1.0	1.1	Liver Tissue	0.9	0.1
(OD04237-01)			6004-N
Lung Margin	3.0	0.4	Liver Cancer	0.5	0.2
(OD04237-02)			6005-T
Ocular Mel Met	0.3	0.0	Liver Tissue	0.0	0.0
to Liver			6005-N
(ODO4310)
Liver Margin	0.0	0.1	Normal	2.9	0.6
(ODO4310)			Bladder
Melanoma Mets	6.5	2.9	Bladder	1.7	37.9
to Lung			Cancer 1023
(OD04321)
Lung Margin	5.9	2.0	Bladder	0.0	0.1
(OD04321)			Cancer
			A302173
Normal Kidney	100.0	57.0	Bladder	0.0	0.3
			Cancer
			(OD04718-01)
Kidney Ca,	3.3	2.6	Bladder	1.7	0.8
Nuclear grade 2			Normal
(OD04338)			Adjacent
			(OD04718-03)
Kidney Margin	64.6	39.0	Normal Ovary	2.2	0.8
(OD04338)
Kidney Ca	0.5	0.1	Ovarian	2.9	1.2
Nuclear grade			Cancer
1/2 (OD04339)			064008
Kidney Margin	65.5	35.4	Ovarian	1.2	2.8
(OD04339)			Cancer
			(OD04768-07)
Kidney Ca,	0.0	0.3	Ovary Margin	4.1	2.2
Clear cell type			(OD04768-08)
(OD04340)
Kidney Margin	62.9	33.2	Normal	41.8	20.3
(OD04340)			Stomach
Kidney Ca,	13.4	5.7	Gastric Cancer	1.0	0.6
Nuclear grade 3			9060358
(OD04348)
Kidney Margin	49.0	21.9	Stomach	29.5	12.8
(OD04348)			Margin
			9060359
Kidney Cancer	25.9	14.2	Gastric Cancer	2.0	1.6
(OD04622-01)			9060395
Kidney Margin	8.1	3.1	Stomach	4.5	2.6
(OD04622-03)			Margin
			9060394
Kidney Cancer	0.1	0.1	Gastric Cancer	0.9	0.1
(OD04450-01)			9060397
Kidney Margin	72.2	42.9	Stomach	2.7	2.7
(OD04450-03)			Margin
			9060396
Kidney Cancer	88.3	44.1	Gastric Cancer	1.3	0.7
8120607			064005

[0537]

TABLE BI
Panel 3D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag2797, Run		Ag2797, Run
Tissue Name	165032015	Tissue Name	165032015
Daoy- Medulloblastoma	0.7	Ca Ski- Cervical epidermoid	5.0
		carcinoma (metastasis)
TE671-	0.0	ES-2- Ovarian clear cell	5.4
Medulloblastoma		carcinoma
D283 Med-	0.2	Ramos- Stimulated with	0.0
Medulloblastoma		PMA/ionomycin 6h
PFSK-1- Primitive	0.0	Ramos- Stimulated with	0.0
Neuroectodermal		PMA/ionomycin 14h
XF-498- CNS	1.8	MEG-01- Chronic	0.0
		myelogenous leukemia
		(megokaryoblast)
SNB-78- Glioma	0.3	Raji- Burkitt's lymphoma	0.0
SF-268- Glioblastoma	1.8	Daudi- Burkitt's lymphoma	0.0
T98G- Glioblastoma	0.1	U266- B-cell plasmacytoma	0.0
SK-N-SH-	0.2	CA46- Burkitt's lymphoma	0.0
Neuroblastoma
(metastasis)
SF-295- Glioblastoma	6.3	RL- non-Hodgkin's B-cell	0.0
		lymphoma
Cerebellum	58.6	JMI- pre-B-cell lymphoma	0.0
Cerebellum	92.7	Jurkat- T cell leukemia	0.0
NCI-H292-	1.2	TF-1- Erythroleukemia	0.0
Mucoepidermoid lung
carcinoma
DMS-114- Small cell	0.0	HUT 78- T-cell lymphoma	0.0
lung cancer
DMS-79- Small cell lung	100.0	U937- Histiocytic lymphoma	0.0
cancer
NCI-H146- Small cell	35.8	KU-812- Myelogenous	0.0
lung cancer		leukemia
NCI-H526- Small cell	0.0	769-P- Clear cell renal	0.0
lung cancer		carcinoma
NCI-N417- Small cell	0.0	Caki-2- Clear cell renal	5.2
lung cancer		carcinoma
NCI-H82- Small cell	0.1	SW 839- Clear cell renal	0.0
lung cancer		carcinoma
NCI-H157- Squamous	41.8	G401- Wilms' tumor	0.1
cell lung cancer
(metastasis)
NCI-H1155- Large cell	1.4	Hs766T- Pancreatic	0.9
lung cancer		carcinoma (LN metastasis)
NCI-H1299- Large cell	1.5	CAPAN-1- Pancreatic	0.0
lung cancer		adenocarcinoma (liver
		metastasis)
NCI-H727- Lung	3.0	SU86.86- Pancreatic	4.5
carcinoid		carcinoma (liver metastasis)
NCI-UMC-11- Lung	17.3	BxPC-3- Pancreatic	0.0
carcinoid		adenocarcinoma
LX-1- Small cell lung	0.0	HPAC- Pancreatic	0.8
cancer		adenocarcinoma
Colo-205- Colon cancer	0.0	MIA PaCa-2- Pancreatic	0.0
		carcinoma
KM12- Colon cancer	0.1	CFPAC-1- Pancreatic ductal	1.3
		adenocarcinoma
KM20L2- Colon cancer	0.0	PANC-1- Pancreatic	0.1
		epithelioid ductal carcinoma
NCI-H716- Colon cancer	0.8	T24- Bladder carcinoma	0.3
		(transitional cell)
SW-48- Colon	0.0	5637- Bladder carcinma	1.5
adenocarcinoma
SW1116- Colon	0.0	HT-1197- Bladder carcinoma	0.0
adenocarcinoma
LS 174T- Colon	0.1	UM-UC-3- Bladder carcinma	1.5
adenocarcinoma		(transitional cell)
SW-948- Colon	0.0	A204- Rhabdomyosarcoma	95.9
adenocarcinoma
SW-480- Colon	0.0	HT-1080- Fibrosarcoma	13.5
adenocarcinoma
NCI-SNU-5- Gastric	0.0	MG-63- Osteosarcoma	10.4
carcinoma
KATO III- Gastric	0.0	SK-LMS-1- Leiomyosarcoma	5.3
carcinoma		(vulva)
NCI-SNU-16- Gastric	1.6	SJRH30-	0.0
carcinoma		Rhabdomyosarcoma (met to
		bone marrow)
NCI-SNU-1- Gastric	0.0	A431- Epidermoid carcinoma	0.0
carcinoma
RF-1- Gastric	0.0	WM266-4- Melanoma	0.3
adenocarcinoma
RF-48- Gastric	0.0	DU 145- Prostate carcinoma	0.0
adenocarcinoma		(brain metastasis)
MKN-45- Gastric	0.0	MDA-MB-468- Breast	0.1
carcinoma		adenocarcinoma
NCI-N87- Gastric	0.3	SCC-4- Squamous cell	0.0
carcinoma		carcinoma of tongue
OVCAR-5- Ovarian	0.1	SCC-9- Squamous cell	0.0
carcinoma		carcinoma of tongue
RL95-2- Uterine	0.4	SCC-15- Squamous cell	0.0
carcinoma		carcinoma of tongue
HelaS3- Cervical	5.3	CAL 27- Squamous cell	0.4
adenocarcinoma		carcinoma of tongue

[0538]

TABLE BJ
Panel 4.1D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag3606, Run		Ag3606, Run
Tissue Name	169943525	Tissue Name	169943525
Secondary Th1 act	0.0	HUVEC IL-1beta	0.7
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	0.8
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	1.0
Secondary Th2 rest	0.3	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC	11.0
		none
Primary Th1 act	0.0	Lung Microvascular EC	14.4
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	1.0
		none
Primary Tr1 act	0.2	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	48.0
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	14.8
		none
Primary Tr1 rest	0.0	Small airway epithelium	7.6
		TNF alpha + IL-1beta
CD45RA CD4	0.7	Coronery artery SMC rest	8.5
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	15.9
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	7.9
Secondary CD8	0.0	Astrocytes TNF alpha +	8.4
lymphocyte rest		IL-1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	0.0
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1—	0.2	CCD1106 (Keratinocytes)	45.1
anti-CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	49.3
		TNF alpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.8
LAK cells IL-2 +	0.3	NCI-H292 none	1.8
IL-12
LAK cells IL-2 +	0.0	NCI-H292 IL-4	2.8
IFN gamma
LAK cells IL-2 +	0.7	NCI-H292 IL-9	2.5
IL-18
LAK cells	0.0	NCI-H292 IL-13	4.2
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	3.2
Two Way MLR 3 day	0.4	HPAEC none	0.3
Two Way MLR 5 day	0.0	HPAEC TNF alpha +	100.0
		IL-1beta
Two Way MLR 7 day	0.4	Lung fibroblast none	0.7
PBMC rest	0.4	Lung fibroblast	88.3
		TNF alpha + IL-1beta
PBMC PWM	0.0	Lung fibroblast IL-4	1.2
PBMC PHA-L	0.0	Lung fibroblast IL-9	2.2
Ramos (B cell) none	0.2	Lung fibroblast IL-13	1.4
Ramos (B cell)	0.0	Lung fibroblast IFN	2.4
ionomycin		gamma
B lymphocytes PWM	0.0	Dermal fibroblast	0.2
		CCD1070 rest
B lymphocytes CD40L	1.7	Dermal fibroblast	1.9
and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	0.3	Dermal fibroblast	7.5
		CCD1070 IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN	0.4
PMA/ionomycin		gamma
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.8
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.0
Dendritic cells anti-	0.2	Neutrophils TNFa + LPS	0.0
CD40
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	36.9	Colon	5.5
Macrophages rest	0.4	Lung	1.9
Macrophages LPS	0.0	Thymus	1.2
HUVEC none	0.2	Kidney	36.3
HUVEC starved	0.0

[0539]

TABLE BK
Panel 4D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag2797, Run		Ag2797, Run
Tissue Name	162291414	Tissue Name	162291414
Secondary Th1 act	0.0	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.1
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	0.3
		gamma
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	1.3
		none
Primary Th1 act	0.0	Lung Microvascular EC	2.7
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	1.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	27.4
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	4.8
		none
Primary Tr1 rest	0.0	Small airway epithelium	6.7
		TNF alpha + IL-1beta
CD45RA CD4	0.2	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	3.3
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	1.8
Secondary CD8	0.0	Astrocytes TNF alpha +	2.5
lymphocyte rest		IL-1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	0.0
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	15.8
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	13.3
		TNF alpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	0.0	Lupus kidney	2.1
LAK cells IL-2 + IFN	0.0	NCI-H292 none	1.3
gamma
LAK cells IL-2 + L-18	0.0	NCI-H292 IL-4	1.2
LAK cells	0.0	NCI-H292 IL-9	100.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IL-13	2.0
Two Way MLR 3 day	0.0	NCI-H292 IFN gamma	1.0
Two Way MLR 5 day	0.0	HPAEC none	1.2
Two Way MLR 7 day	0.0	HPAEC TNF alpha +	28.7
		IL-1beta
PBMC rest	0.0	Lung fibroblast none	0.3
PBMC PWM	0.1	Lung fibroblast	29.9
		TNF alpha + IL-1beta
PBMC PHA-L	0.0	Lung fibroblast IL-4	0.7
Ramos (B cell) none	0.0	Lung fibroblast IL-9	0.9
Ramos (B cell)	0.0	Lung fibroblast IL-13	0.7
ionomycin
B lymphocytes PWM	0.0	Lung fibroblast IFN	0.7
		gamma
B lymphocytes CD40L	0.0	Dermal fibroblast	0.5
and IL-4		CCD1070 rest
EOL-1 dbcAMP	0.0	Dermal fibroblast	2.0
		CCD1070 TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast	3.3
PMA/ionomycin		CCD1070 IL-1beta
Dendritic cells none	0.0	Dermal fibroblast IFN	0.0
		gamma
Dendritic cells LPS	0.0	Dermal fibroblast IL-4	0.3
Dendritic cells anti-	0.0	IBD Colitis 2	0.0
CD40
Monocytes rest	0.2	IBD Crohn's	0.1
Monocytes LPS	5.4	Colon	2.4
Macrophages rest	0.0	Lung	0.4
Macrophages LPS	0.0	Thymus	21.9
HUVEC none	0.2	Kidney	0.0
HUVEC starved	0.1

[0540]

TABLE BL
Panel CNS_1
	Rel. Exp.(%) Ag2797,		Rel. Exp.(%) Ag2797,
Tissue Name	Run 171664308	Tissue Name	Run 171664308
BA4 Control	14.1	BA17 PSP	16.0
BA4 Control2	27.5	BA17 PSP2	6.4
BA4	2.4	Sub Nigra Control	61.6
Alzheimer's2
BA4 Parkinson's	28.1	Sub Nigra Control2	68.8
BA4	33.4	Sub Nigra	25.3
Parkinson's2		Alzheimer's2
BA4	28.5	Sub Nigra	73.7
Huntington's		Parkinson's2
BA4	3.3	Sub Nigra	100.0
Huntington's2		Huntington's
BA4 PSP	6.6	Sub Nigra	39.2
		Huntington's2
BA4 PSP2	15.5	Sub Nigra PSP2	15.1
BA4 Depression	7.3	Sub Nigra	8.8
		Depression
BA4	3.9	Sub Nigra	8.8
Depression2		Depression2
BA7 Control	24.1	Glob Palladus	17.0
		Control
BA7 Control2	27.4	Glob Palladus	8.6
		Control2
BA7	4.1	Glob Palladus	24.8
Alzheimer's2		Alzheimer's
BA7 Parkinson's	7.2	Glob Palladus	5.5
		Alzheimer's2
BA7	16.6	Glob Palladus	54.0
Parkinson's2		Parkinson's
BA7	23.3	Glob Palladus	16.2
Huntington's		Parkinson's2
BA7	18.6	Glob Palladus PSP	7.9
Huntington's2
BA7 PSP	21.8	Glob Palladus PSP2	8.6
BA7 PSP2	12.9	Glob Palladus	4.6
		Depression
BA7 Depression	4.6	Temp Pole Control	8.3
BA9 Control	15.0	Temp Pole Control2	36.3
BA9 Control2	43.5	Temp Pole	3.3
		Alzheimer's
BA9 Alzheimer's	3.1	Temp Pole	3.3
		Alzheimer's2
BA9	5.5	Temp Pole	13.2
Alzheimer's2		Parkinson's
BA9 Parkinson's	18.2	Temp Pole	15.0
		Parkinon's2
BA9	28.9	Temp Pole	22.4
Parkinson's2		Huntington's
BA9	37.6	Temp Pole PSP	1.9
Huntington's
BA9	8.7	Temp Pole PSP2	2.2
Huntington's2
BA9 PSP	9.3	Temp Pole	4.3
		Depression2
BA9 PSP2	2.6	Cing Gyr Control	33.7
BA9 Depression	1.5	Cing Gyr Control2	24.1
BA9	3.5	Cing Gyr	16.4
Depression2		Alzheimer's
BA17 Control	16.4	Cing Gyr	8.7
		Alzheimer's2
BA17 Control2	28.9	Cing Gyr	27.9
		Parkinson's
BA17	3.0	Cing Gyr	27.0
Alzheimer's2		Parkinson's2
BA17	20.2	Cing Gyr	54.3
Parkinson's		Huntington's
BA17	17.1	Cing Gyr	18.6
Parkinson's2		Huntington's2
BA17	24.0	Cing Gyr PSP	17.1
Huntington's
BA17	8.2	Cing Gyr PSP2	4.6
Huntington's2
BA17	7.5	Cing Gyr	6.0
Depression		Depression
BA17	12.3	Cing Gyr	8.6
Depression2		Depression2

[0541] CNS_neurodegeneration_v1.0 Summary: Ag3606 This panel does not show differential expression of the CG59843-01 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain, with highest expression in the temporal cortex of an Alzheimer's patient (CT=26.3). Please see Panel 1.4 for discussion of utility of this gene in the central nervous system. Results from a second experiment using the probe and primer set Ag2797 are not included. The amp plot indicates that there were experimental difficulties with this run.

[0542] General_screening_panel_v1.4 Summary: Ag3606 Highest expresson of the CG59843-01 gene is seen in a brain cancer cell line (CT=24). In addition, this gene also shows highly brain preferential expression, with high levels of expression in all CNS regions represented on this panel. Therefore, expression of this gene could be used to differentiate between brain derived samples and other samples on this panel. Furthermore, 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.

[0543] High levels of expression are also seen in samples derived from melanoma, lung and brain cancer cell lines. Thus, expression of this gene could be used as a marker for these types of cancers. This gene encodes a fibropellin-like molecule. Fibropellins are glycoproteins that may be involved in cell adhesion. Therefore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of melanoma, lung and brain cancers.

[0544] See, generally,

[0545] Burke R D, Lail M, Nakajima Y. The apical lamina and its role in cell adhesion in sea urchin embryos. Cell Adhes Commun 1998 March;5(2):97-108. PMID: 9638331

[0546] Panel 1 Summary: Ag221 Expression in this panel is in agreement with the profile seen in Panel 1.4. The CG59843-01 gene shows highly brain preferential expression, with highest expression in the cerebellum (CT=21.4). Please see Panel 1.4 for discussion of utility of this gene in the central nervous system.

[0547] Panel 1.3D Summary: Ag2797 Two experiments with the same probe and primer set produce results that are in excellent agreement, with highest expression in the thalamus (CTs=24.5-25.5).

[0548] High levels of expression are also seen in samples derived from melanoma, lung and brain cancer cell lines. Please see Panel 1.4 for further discussion of utility of this gene in the CNS and cancer.

[0549] Moderate to low levels of expression are also seen in the adrenal, pituitary, fetal heart, and fetal skeletal muscle. This expression in metabolic tissues suggests that this gene product may be involved in the pathogenesis and/or treatment of metabolic disorders, including obesity and diabetes.

[0550] Panel 2D Summary: Ag2797 Two experiments with the same probe and primer set produce results that are in excellent agreement. Highest expresson of the CG59843-01 gene is seen in kidney (CTs=28). The expression of this gene is down-regulated in kidney cancers (CTs=31-38), gastric cancer and colon cancer as compared to control margin (CTs=28-3 1). Therefore, expression of this gene could be used to distinguish between normal kidney, stomach and colon tissue from cancer samples.

[0551] In addition significant expression of this gene is also seen in breast cancer, bladder cancer, lung malignant cancer, and prostate cancer samples. Thus, therapeutic modulation of this gene, through the use of small molecule drugs, and antibodies could be of benefit in the treatment of bladder, breast, kidney or lung cancer.

[0552] Panel 3D Summary: Ag2797 Highest expression of the CG59843-01 gene is seen in a small cell lung cancer cell line (CT=25). Significant levels of expression are also seen in the cerebellum. This is in agreement with the highly brain preferential expression profiles seen in the previous panels. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel. In addition, significant expression of this gene is associated with squamous cell lung cancer, large cell lung cancer, lung carcinoid, rhabdomyosarcoma, fibrosarcoma, osteosarcoma, medulloblastoma, leiomyosarcoma, cervical and pancreatic cancers. Therefore, therapeutic modulation of this gene or its product, through the use of small molecule drugs, and antibodies could be of benefit in the treatment of these cancers.

[0553] Panel 4.1D Summary: Ag3606/2797 The CG59843-01 gene was reproducibly expressed, as displayed on Panels 4D and 4.1D, across several activated cell types that model lung inflammatory diseases. These include cytokine-activated lung fibroblasts, cytokine-activated pulmonary aortic endothelial cells, and cytokine-activated bronchial epithelial cells (CTs=28-31). Therefore, therapeutic modulation of this gene or its product, through the use of small molecule drugs, and antibodies, may reduce or eliminate the symptoms of inflammatory lung diseases, such as, but not limited to, asthma, emphysema, and chronic obstructive pulmonary disease.

[0554] Panel 4D Summary: See annotation for Panel 4.1D for relevant comments.

[0555] Panel CNS—1 Summary: Ag3606 This panel confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of utility of this gene in the central nervous system.

[0556] C. NOV3a (CG59845-01: butyrophilin)

[0557] Expression of gene CG59845-01 was assessed using the primer-probe set Ag3607, described in Table CA. Results of the RTQ-PCR runs are shown in Table CB.

TABLE CA
Probe Name Ag3607
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-attccaagtcaatggtcaaaca-3′	22	46	111
Probe	TET-5′-actcgcatctctcacatcacccactt-3′-TAMRA	26	72	112
Reverse	5′-cgaaaggatgagaagaggaagt-3′	22	120	113

[0558]

TABLE CB
Panel 4.1D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag3607, Run		Ag3607, Run
Tissue Name	169943563	Tissue Name	169943563
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	0.0
		gamma
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	0.0
		none
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	0.0
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	0.0
		none
Primary Tr1 rest	0.0	Small airway epithelium	0.0
		TNF alpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	0.0
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes TNF alpha +	0.0
lymphocyte rest		IL-1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	0.0
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNF alpha + 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	0.0	NCI-H292 IL-4	0.0
gamma
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells	100.0	NCI-H292 IL-13	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.0	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha +	0.0
		IL-1beta
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
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)	0.0	Lung fibroblast IFN	0.0
ionomycin		gamma
B lymphocytes PWM	0.0	Dermal fibroblast	0.0
		CCD1070 rest
B lymphocytes CD40L	0.0	Dermal fibroblast	0.0
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 IFN	0.0
PMA/ionomycin		gamma
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.0
Dendritic cells anti-	0.0	Neutrophils TNFa + LPS	0.0
CD40
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	0.0
Macrophages rest	0.0	Lung	0.0
Macrophages LPS	0.0	Thymus	0.0
HUVEC none	0.0	Kidney	0.0
HUVEC starved	0.0

[0559] CNS_neurodegeneration_v1.0 Summary: Ag3607 Expression of the CG59845-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0560] General_screening_panel_v1.4 Summary: Ag3607 Expression of the CG59845-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0561] Panel 4.1D Summary: Ag3607 Highest expression of the CG59845-01 gene is seen exclusively in PMA/ionomycin treated LAK cells (CT=33.5). Therefore, expression of this gene can be used in distinguishing this sample from other samples in this panel. LAK cells are involved in tumor immunology and cell clearance of virally and bacterial infected cells as well as tumors. Therefore, modulation of the function of the protein encoded by this gene through the application of a small molecule drug or antibody may alter the functions of these cells and lead to improvement of symptoms associated with these conditions

[0562] D. NOV4a (CG59871-01: CVB3 BINDING PROTEIN)

[0563] Expression of gene CG59871-01 was assessed using the primer-probe sets Ag3806 and Ag3808, described in Tables DA and DB. Results of the RTQ-PCR runs are shown in Tables DC, DD and DE.

TABLE DA
Probe Name Ag3806
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-agtggatttcgccagaagtt-3′	20	460	114
Probe	TET-5′-tgagtatcactactcctgaagagatgattg-3′-TAMRA	30	480	115
Reverse	5′-atggcagataggcagtttcc-3′	20	523	116

[0564]

TABLE DB
Probe Name Ag3808
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-gtggatttcgccagaagttt-3′	20	461	117
Probe	TET-5′-aaaagccaaaggggaaactgcctatc-3′-TAMRA	26	511	118
Reverse	5′-taagcgtaaatttgcatggc-3′	20	538	119

[0565]

TABLE DC
CNS_neurodegeneration_v1.0
	Rel. Exp.(%) Ag3806,		Rel. Exp.(%) Ag3806,
Tissue Name	Run 211292375	Tissue Name	Run 211292375
AD 1 Hippo	8.8	Control (Path) 3	2.1
		Temporal Ctx
AD 2 Hippo	27.4	Control (Path) 4	29.5
		Temporal Ctx
AD 3 Hippo	4.9	AD 1 Occipital Ctx	18.0
AD 4 Hippo	11.4	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	57.8	AD 3 Occipital Ctx	3.7
AD 6 Hippo	100.0	AD 4 Occipital Ctx	17.1
Control 2 Hippo	30.6	AD 5 Occipital Ctx	38.4
Control 4 Hippo	9.5	AD 6 Occipital Ctx	34.4
Control (Path) 3	9.0	Control 1 Occipital	3.0
Hippo		Ctx
AD 1 Temporal Ctx	15.2	Control 2 Occipital	49.0
		Ctx
AD 2 Temporal Ctx	32.5	Control 3 Occipital	17.1
		Ctx
AD 3 Temporal Ctx	4.1	Control 4 Occipital	7.4
		Ctx
AD 4 Temporal Ctx	13.2	Control (Path) 1	82.9
		Occipital Ctx
AD 5 Inf Temporal	66.9	Control (Path) 2	6.0
Ctx		Occipital Ctx
AD 5 Sup	36.9	Control (Path) 3	1.3
Temporal Ctx		Occipital Ctx
AD 6 Inf Temporal	73.7	Control (Path) 4	14.0
Ctx		Occipital Ctx
AD 6 Sup	71.2	Control 1 Parietal	5.1
Temporal Ctx		Ctx
Control 1 Temporal	3.0	Control 2 Parietal	28.9
Ctx		Ctx
Control 2 Temporal	28.9	Control 3 Parietal	12.7
Ctx		Ctx
Control 3 Temporal	16.2	Control (Path) 1	73.7
Ctx		Parietal Ctx
Control 3 Temporal	4.8	Control (Path) 2	18.2
Ctx		Parietal Ctx
Control (Path) 1	56.6	Control (Path) 3	2.3
Temporal Ctx		Parietal Ctx
Control (Path) 2	75.8	Control (Path) 4	36.3
Temporal Ctx		Parietal Ctx

[0566]

TABLE DD
General_screening_panel_v1.4
	Rel. Exp.(%) Ag3808,		Rel. Exp.(%) Ag3808,
Tissue Name	Run 218667401	Tissue Name	Run 218667401
Adipose	4.9	Renal ca. TK-10	30.4
Melanoma*	0.0	Bladder	40.6
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	25.3
Hs688(B).T		NCI-N87
Melanoma* M14	0.1	Gastric ca. KATO III	54.7
Melanoma*	0.4	Colon ca. SW-948	19.6
LOXIMVI
Melanoma* SK-	17.7	Colon ca. SW480	63.7
MEL-5
Squamous cell	8.7	Colon ca.* (SW480	12.5
carcinoma SCC-4		met) SW620
Testis Pool	12.8	Colon ca. HT29	13.7
Prostate ca.* (bone	0.7	Colon ca. HCT-116	15.2
met) PC-3
Prostate Pool	11.4	Colon ca. CaCo-2	100.0
Placenta	0.1	Colon cancer tissue	29.9
Uterus Pool	3.1	Colon ca. SW1116	6.9
Ovarian ca.	53.6	Colon ca. Colo-205	0.1
OVCAR-3
Ovarian ca. SK-OV-3	1.7	Colon ca. SW-48	14.8
Ovarian ca.	31.6	Colon Pool	3.7
OVCAR-4
Ovarian ca.	22.7	Small Intestine Pool	3.7
OVCAR-5
Ovarian ca. IGROV-1	14.8	Stomach Pool	4.8
Ovarian ca.	14.5	Bone Marrow Pool	3.5
OVCAR-8
Ovary	3.5	Fetal Heart	14.3
Breast ca. MCF-7	0.1	Heart Pool	6.0
Breast ca. MDA-	10.4	Lymph Node Pool	5.1
MB-231
Breast ca. BT 549	95.9	Fetal Skeletal Muscle	0.1
Breast ca. T47D	49.7	Skeletal Muscle Pool	0.1
Breast ca. MDA-N	0.1	Spleen Pool	0.8
Breast Pool	4.8	Thymus Pool	3.4
Trachea	8.1	CNS cancer (glio/	0.9
		astro) U87-MG
Lung	0.2	CNS cancer (glio/	0.1
		astro) U-118-MG
Fetal Lung	25.3	CNS cancer	10.3
		(neuro; met) SK-N-AS
Lung ca. NCI-N417	3.2	CNS cancer (astro)	1.2
		SF-539
Lung ca. LX-1	14.4	CNS cancer (astro)	0.9
		SNB-75
Lung ca. NCI-H146	6.5	CNS cancer (glio)	17.1
		SNB-19
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-	12.9
		295
Lung ca. A549	10.2	Brain (Amygdala)	9.5
		Pool
Lung ca. NCI-H526	10.5	Brain (cerebellum)	2.2
Lung ca. NCI-H23	60.7	Brain (fetal)	74.7
Lung ca. NCI-H460	10.9	Brain (Hippocampus)	9.3
		Pool
Lung ca. HOP-62	26.2	Cerebral Cortex Pool	11.0
Lung ca. NCI-H522	59.0	Brain (Substantia	9.3
		nigra) Pool
Liver	3.8	Brain (Thalamus) Pool	16.0
Fetal Liver	27.4	Brain (whole)	14.7
Liver ca. HepG2	51.8	Spinal Cord Pool	10.7
Kidney Pool	6.7	Adrenal Gland	2.4
Fetal Kidney	18.2	Pituitary gland Pool	4.9
Renal ca. 786-0	0.5	Salivary Gland	6.0
Renal ca. A498	2.0	Thyroid (female)	13.1
Renal ca. ACHN	0.0	Pancreatic ca.	9.0
		CAPAN2
Renal ca. UO-31	1.6	Pancreas Pool	10.7

[0567]

TABLE DE
Panel 4.1D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag3806, Run		Ag3806, Run
Tissue Name	169997727	Tissue Name	169997727
Secondary Th1 act	2.6	HUVEC IL-1beta	14.0
Secondary Th2 act	5.3	HUVEC IFN gamma	12.6
Secondary Tr1 act	15.7	HUVEC TNF alpha + IFN	3.5
		gamma
Secondary Th1 rest	0.4	HUVEC TNF alpha + IL4	14.1
Secondary Th2 rest	0.2	HUVEC IL-11	11.1
Secondary Tr1 rest	0.3	Lung Microvascular EC	5.8
		none
Primary Th1 act	0.4	Lung Microvascular EC	0.3
		TNF alpha + IL-1beta
Primary Th2 act	1.1	Microvascular Dermal EC	47.3
		none
Primary Tr1 act	0.2	Microsvasular Dermal EC	1.4
		TNF alpha + IL-1beta
Primary Th1 rest	0.4	Bronchial epithelium	72.7
		TNF alpha + IL-1beta
Primary Th2 rest	0.4	Small airway epithelium	54.7
		none
Primary Tr1 rest	0.3	Small airway epithelium	69.7
		TNF alpha + IL-1beta
CD45RA CD4	0.7	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	1.5	Coronery artery SMC	0.0
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	1.5	Astrocytes rest	18.6
Secondary CD8	0.6	Astrocytes TNF alpha +	9.6
lymphocyte rest		IL-1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	10.2
lymphocyte act
CD4 lymphocyte none	0.9	KU-812 (Basophil)	9.9
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	17.8
CD95 CH11		none
LAK cells rest	1.5	CCD1106 (Keratinocytes)	20.7
		TNF alpha + IL-1beta
LAK cells IL-2	0.4	Liver cirrhosis	69.7
LAK cells IL-2 + IL-12	1.8	NCI-H292 none	31.2
LAK cells IL-2 + IFN	1.9	NCI-H292 IL-4	63.7
gamma
LAK cells IL-2 + IL-18	1.3	NCI-H292 IL-9	85.3
LAK cells	0.0	NCI-H292 IL-13	72.2
PMA/ionomycin
NK Cells IL-2 rest	0.2	NCI-H292 IFN gamma	74.7
Two Way MLR 3 day	0.7	HPAEC none	8.1
Two Way MLR 5 day	1.5	HPAEC TNF alpha + IL-1	1.5
		beta
Two Way MLR 7 day	0.4	Lung fibroblast none	10.0
PBMC rest	0.9	Lung fibroblast	3.7
		TNF alpha + IL-1beta
PBMC PWM	1.1	Lung fibroblast IL-4	9.3
PBMC PHA-L	0.0	Lung fibroblast IL-9	14.6
Ramos (B cell) none	12.0	Lung fibroblast IL-13	8.9
Ramos (B cell)	8.4	Lung fibroblast IFN	5.0
ionomycin		gamma
B lymphocytes PWM	0.4	Dermal fibroblast	0.4
		CCD1070 rest
B lymphocytes CD40L	0.7	Dermal fibroblast	0.9
and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	8.8	Dermal fibroblast	0.0
		CCD1070 IL-1beta
EOL-1 dbcAMP	3.0	Dermal fibroblast IFN	0.3
PMA/ionomycin		gamma
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.4
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.6
Dendritic cells anti-	0.0	Neutrophils TNFa + LPS	0.0
CD40
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	100.0
Macrophages rest	5.5	Lung	39.0
Macrophages LPS	0.0	Thymus	24.1
HUVEC none	39.5	Kidney	50.7
HUVEC starved	45.4

[0568] CNS_neurodegeneration_v1.0 Summary: Ag3806 This panel confirms the expression of the CG59871-01 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. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.

[0569] General_screening_panel_v1.4 Summary: Ag3806 Highest expression of the CG59871-01 gene is detected in colon cancer CaCo-2 cell line (CT=26.3). In addition high expression of this gene is also seen in cluster of colon cancer, CNS cancer, gastric cancer, lung cancer, breast and ovarian cancers, squamous cell line carcinoma and a melanoma cell lines. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, might be beneficial in the treatment of these cancers.

[0570] 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.

[0571] Interestingly, this gene is expressed at much higher levels in fetal (CTs=28) when compared to adult lung and liver samples (CTs=33-35). This observation suggests that expression of this gene can be used to distinguish fetal lung and liver from corresponding adult tissues.

[0572] In addition, this gene is expressed at high to 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. Furthermore, expression of this gene is higher in fetal (CT=26) as compared to the adult whole brain (CT=29). Therefore, expression of this gene can be used to distinguish fetal from adult brain.

[0573] Panel 4.1D Summary: Ag3806 Highest expression of the CG59871-01 gene is detected in colon sample(CT=30). In addition, significant expression of this gene is seen in normal lung, thymus and kidney tissues. Therefore, antibody or small molecule therapies designed with the protein encoded for by this gene could modulate these tissue function and be important in the treatment of inflammatory or autoimmune diseases that affect these tissues such as, lupus and glomerulonephritis, inflammatory bowel diseases, asthma, allergy, COPD and emphysema.

[0574] High expression of this gene is also seen in NCI-H292, small airway epithelium, microvascular dermal EC, TNFalpha+IL1beta treated bronchial epithelium, HUVEC, EOL-1 dbcAMP, Ramos (B cells) and activated secondary Tr1 cells. The expression of this gene in cells derived from or within the lung, in activated T and B cells suggests that this gene may be involved in normal conditions, as well as, pathological and inflammatory lung disorders that include chronic obstructive pulmonary disease, asthma, allergy and emphysema.

[0575] E. NOV5a (CG59883-01: CVB3 BINDING PROTEIN)

[0576] Expression of gene CG59883-01 was assessed using the primer-probe set Ag3625, described in Table EA. Results of the RTQ-PCR runs are shown in Tables EB, and EC.

TABLE EA
Probe Name Ag3625
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-tcatccctgggatccatatc-3′	20	1069	120
Probe	TET-5′-tccttccaacatggaaggatattcca-3′-TAMRA	26	1089	121
Reverse	5′-gtgcgttcaaagtcttcacttg-3′	22	1136	122

[0577]

TABLE EB
General_screening_panel_v1.4
	Rel. Exp.(%) Ag3625,		Rel. Exp.(%) Ag3625,
Tissue Name	Run 218211650	Tissue Name	Run 218211650
Adipose	0.0	Renal ca. TK-10	0.0
Melanoma*	0.0	Bladder	0.0
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.8
Melanoma*	0.0	Colon ca. SW-948	0.0
LOXIMVI
Melanoma* SK-	0.0	Colon ca. SW480	0.0
MEL-5
Squamous cell	0.0	Colon ca.* (SW480	0.0
carcinoma SCC-4		met) SW620
Testis Pool	100.0	Colon ca. HT29	0.0
Prostate ca.* (bone	0.3	Colon ca. HCT-116	0.0
met) PC-3
Prostate Pool	1.6	Colon ca. CaCo-2	0.0
Placenta	0.0	Colon cancer tissue	0.3
Uterus Pool	0.0	Colon ca. SW1116	0.0
Ovarian ca.	0.0	Colon ca. Colo-205	0.0
OVCAR-3
Ovarian ca. SK-OV-3	1.6	Colon ca. SW-48	0.0
Ovarian ca.	0.2	Colon Pool	0.4
OVCAR-4
Ovarian ca.	0.0	Small Intestine Pool	0.1
OVCAR-5
Ovarian ca. IGROV-1	1.3	Stomach Pool	0.3
Ovarian ca.	0.4	Bone Marrow Pool	0.0
OVCAR-8
Ovary	0.2	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-	0.0	Lymph Node Pool	0.5
MB-231
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.5	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.2	Spleen Pool	0.0
Breast Pool	0.2	Thymus Pool	1.1
Trachea	0.2	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	0.0	CNS cancer (glio/astro)	0.4
		U-118-MG
Fetal Lung	0.0	CNS cancer	0.0
		(neuro;met) SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-	2.0
		539
Lung ca. LX-1	0.0	CNS cancer (astro)	26.1
		SNB-75
Lung ca. NCI-H146	0.0	CNS cancer (glio)	0.4
		SNB-19
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-	0.2
		295
Lung ca. A549	0.0	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.0
Lung ca. NCI-H23	0.4	Brain (fetal)	0.0
Lung ca. NCI-H460	0.3	Brain (Hippocampus)	0.4
		Pool
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.7
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	0.2
		Pool
Liver	0.0	Brain (Thalamus) Pool	0.5
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	0.0	Spinal Cord Pool	0.2
Kidney Pool	0.1	Adrenal Gland	0.3
Fetal Kidney	0.0	Pituitary gland Pool	0.1
Renal ca. 786-0	0.0	Salivary Gland	0.0
Renal ca. A498	1.8	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca.	0.0
		CAPAN2
Renal ca. UO-31	0.1	Pancreas Pool	0.8

[0578]

TABLE ED
Panel 4.1D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag3625, Run		Ag3625, Run
Tissue Name	169946001	Tissue Name	169946001
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	0.0
		gamma
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	0.9
		none
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	0.0
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	0.0
		none
Primary Tr1 rest	0.0	Small airway epithelium	0.0
		TNF alpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	3.1	Coronery artery SMC	0.0
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes TNF alpha +	0.0
lymphocyte rest		IL-1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	0.0
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	4.8
CD95 CH11		none
LAK cells rest	0.7	CCD1106 (Keratinocytes)	4.4
		TNF alpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	2.4
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	72.7
LAK cells IL-2 + IFN	0.0	NCI-H292 IL-4	93.3
gamma
LAK cells IL-2 + IL-18	2.4	NCI-H292 IL-9	100.0
LAK cells	0.0	NCI-H292 IL-13	94.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	74.7
Two Way MLR 3 day	2.1	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1	0.0
		beta
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	0.0	Lung fibroblast TNF alpha	0.0
		+ 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)	0.0	Lung fibroblast IFN	0.0
ionomycin		gamma
B lymphocytes PWM	0.0	Dermal fibroblast	0.0
		CCD1070 rest
B lymphocytes CD40L	0.0	Dermal fibroblast	0.0
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 IFN	0.0
PMA/ionomycin		gamma
Dendritic cells none	2.6	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.0
Dendritic cells anti-	1.7	Neutrophils TNFa + LPS	2.3
CD40
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	0.0
Macrophages rest	0.0	Lung	1.1
Macrophages LPS	0.0	Thymus	6.3
HUVEC none	0.0	Kidney	0.0
HUVEC starved	0.0

[0579] CNS_neurodegeneration_v1.0 Summary: Ag3625 Expression of the CG59883-01 gene is low/undetectable in all samples on this panel (CTs>35).

[0580] General_screening_panel_v1.4 Summary: Ag3625 Expression of the CG59883-01 gene is restricted to the testis and a brain cancer cell line (CTs=30-32). Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker of testicular tissue. Furthermore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of male infertility and hypogonadism.

[0581] Panel 4.1D Summary: Ag3625 Expression of the CG59883-01 gene is restricted to a cluster of treated and untreated NCI-H292 mucoepidermoid cells (CTs=32-33). Treatment of these cells does not seem to significantly alter expression of this transcript in this cell line. Thus, the protein could be used to identify certain lung tumors similar to NCI-H292. The encoded protein may also contribute to the normal function of the goblet cells within the lung. Therefore, designing therapeutics to this protein may be important for the treatment of emphysema and asthma as well as other lung diseases in which goblet cells or the mucus they produce have pathological consequences.

[0582] F. NOV6a (CG59901-01: Scavenger receptor)

[0583] Expression of gene CG59901-01 was assessed using the primer-probe set Ag3627, described in Table FA.

TABLE FA
Probe Name Ag3627
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-ggagcagtgactgctgtagaga-3′	22	331	123
Probe	TET-5′-caccctctctggactaccctggtctg-3′-TAMRA	26 356	124
Reverse	5′-agcattcacacgacgtaaatgt-3′	22	388	125

[0584] CNS_neurodegeneration_v1.0 Summary: Ag3627 Expression of the CG59901-01 gene is low/undetectable in all samples on this panel (CTs>35).

[0585] General_screening_panel_v1.4 Summary: Ag3627 Expression of the CG59901-01 gene is low/undetectable in all samples on this panel (CTs>35).

[0586] Panel 4.1D Summary: Ag3627 Expression of the CG59901-01 gene is low/undetectable in all samples on this panel (CTs>35).

[0587] G. NOV7a (CG88748-01: cyclic nucleotide-gated channel protein)

[0588] Expression of gene CG88748-01 was assessed using the primer-probe set Ag3677, described in Table GA. Results of the RTQ-PCR runs are shown in Tables GB.

TABLE GA
Probe Name Ag3677
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-acagtggatgagcgagaaatt-3′	21	1328	126
	TET-5′-ctcaagaatctgccagccaagctcag-3′-
Probe	TAMRA	26	1349	127
Reverse	5′-caagtggacattgatggctatc-3′	22	1381	128

[0589]

TABLE GB
General_screening_panel_v1.4
	Rel. Exp.(%) Ag3677,		Rel. Exp.(%) Ag3677,
Tissue Name	Run 218952040	Tissue Name	Run 218952040
Adipose	0.0	Renal ca. TK-10	0.0
Melanoma*	0.0	Bladder	0.0
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma*	0.0	Colon ca. SW-948	0.0
LOXIMVI
Melanoma* SK-	0.0	Colon ca. SW480	0.0
MEL-5
Squamous cell	0.0	Colon ca.* (SW480	0.0
carcinoma SCC-4		met) SW620
Testis Pool	100.0	Colon ca. HT29	0.0
Prostate ca.* (bone	0.0	Colon ca. HCT-116	0.0
met) PC-3
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.	0.0	Colon ca. Colo-205	0.0
OVCAR-3
Ovarian ca. SK-OV-3	0.0	Colon ca. SW-48	0.0
Ovarian ca.	0.0	Colon Pool	7.9
OVCAR-4
Ovarian ca.	0.0	Small Intestine Pool	0.0
OVCAR-5
Ovarian ca. IGROV-1	0.0	Stomach Pool	0.0
Ovarian ca.	0.0	Bone Marrow Pool	0.0
OVCAR-8
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	6.6
Breast ca. MDA-	0.0	Lymph Node Pool	0.0
MB-231
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	8.2	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	9.7	Spleen Pool	0.0
Breast Pool	0.0	Thymus Pool	16.7
Trachea	0.0	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	0.0	CNS cancer (glio/astro)	0.0
		U-118-MG
Fetal Lung	0.0	CNS cancer	0.0
		(neuro; met) SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-	0.0
		539
Lung ca. LX-1	9.1	CNS cancer (astro)	0.0
		SNB-75
Lung ca. NCI-H146	0.0	CNS cancer (glio)	0.0
		SNB-19
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-	0.0
		295
Lung ca. A549	0.0	Brain (Amygdala) Pool	0.0
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 (Hippocampus)	0.0
		Pool
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	0.0
		Pool
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	0.0	Spinal Cord Pool	0.0
Kidney Pool	33.7	Adrenal Gland	13.0
Fetal Kidney	9.6	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	5.6

[0590] Table GD. Panel 4.1D

[0591] CNS_neurodegeneration_v1.0 Summary: Ag3677 Expression of the CG88748-01 gene is low/undetectable in all samples on this panel (CTs>35).

[0592] General_screening_panel_v1.4 Summary: Ag3677 Expression of the CG88748-01 gene is restricted to the testis (CT=33.8). Therefore, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker of testicular tissue. Furthermore, thereapeutic modulation of the expression or function of this gene may be effective in the treatment of male infertility or hypogonadism.

[0593] Panel 4.1D Summary: Ag3677 Expression of the CG88748-01 gene is low/undetectable in all samples on this panel (CTs>35).

[0594] H. NOV8a (CG90021-01: Testicular Metalloprotease-Like, Disintegrin-Like.)

[0595] Expression of gene CG90021-01 was assessed using the primer-probe set Ag3701, described in Table HA. Results of the RTQ-PCR runs are shown in Tables HB and HC.

TABLE HA
Probe Name Ag3701
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-caatataaaaggccacgttcaa-3′	22	665	129
Probe	TET-5′-tccaattcatattatcgcatatatggca-3′-	28	690	130
	TAMRA
Reverse	5′-gaccacctctttggaacaagtt-3′	22	725	131

[0596]

TABLE HB
General_screening_panel_v1.4
	Rel. Exp.(%) Ag3701,		Rel. Exp.(%) Ag3701,
Tissue Name	Run 218253707	Tissue Name	Run 218253707
Adipose	0.0	Renal ca. TK-10	0.0
Melanoma*	0.0	Bladder	0.0
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma*	0.0	Colon ca. SW-948	0.0
LOXIMVI
Melanoma* SK-	0.0	Colon ca. SW480	0.0
MEL-5
Squamous cell	0.0	Colon ca.* (SW480	0.0
carcinoma SCC-4		met) SW620
Testis Pool	100.0	Colon ca. HT29	0.0
Prostate ca.* (bone	0.0	Colon ca. HCT-116	0.0
met) PC-3
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.	0.0	Colon ca. Colo-205	0.0
OVCAR-3
Ovarian ca. SK-OV-3	0.0	Colon ca. SW-48	0.0
Ovarian ca.	0.0	Colon Pool	0.0
OVCAR-4
Ovarian ca.	0.0	Small Intestine Pool	0.0
OVCAR-5
Ovarian ca. IGROV-1	0.0	Stomach Pool	0.0
Ovarian ca.	0.0	Bone Marrow Pool	0.0
OVCAR-8
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-	0.0	Lymph Node Pool	0.0
MB-231
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	0.0	Thymus Pool	0.0
Trachea	0.0	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	0.0	CNS cancer (glio/astro)	0.0
		U-118-MG
Fetal Lung	0.0	CNS cancer	0.0
		(neuro;met) SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-	0.0
		539
Lung ca. LX-1	0.0	CNS cancer (astro)	0.0
		SNB-75
Lung ca. NCI-H146	0.0	CNS cancer (glio)	0.0
		SNB-19
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-	0.0
		295
Lung ca. A549	0.0	Brain (Amygdala) Pool	0.0
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 (Hippocampus)	0.0
		Pool
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	0.0
		Pool
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	0.0	Spinal Cord Pool	0.0
Kidney Pool	0.0	Adrenal Gland	0.0
Fetal Kidney	0.0	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

[0597]

TABLE HC
Panel 4.1D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag3701, Run		Ag3701, Run
Tissue Name	169987419	Tissue Name	169987419
Secondary Th1 act	100.0	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.3	HUVEC TNF alpha + IFN	0.0
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.3	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC	0.0
		none
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.2
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	0.0
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	0.0
		none
Primary Tr1 rest	0.0	Small airway epithelium	0.0
		TNF alpha + IL-1beta
CD45RA CD4	0.4	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	0.0
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes TNF alpha +	0.0
lymphocyte rest		IL-1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	0.0
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNF alpha + 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	0.0	NCI-H292 IL-4	0.0
gamma
LAK cells IL-2+ IL-18	0.0	NCI-H292 IL-9	0.0
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 3 day	0.0	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1	0.0
		beta
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	0.0	Lung fibroblast TNF	0.0
		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)	0.0	Lung fibroblast IFN	0.0
ionomycin		gamma
B lymphocytes PWM	0.0	Dermal fibroblast	0.0
		CCD1070 rest
B lymphocytes CD40L	0.0	Dermal fibroblast	0.0
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 IFN	0.0
PMA/ionomycin		gamma
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.0
Dendritic cells anti-	0.0	Neutrophils TNFa + LPS	0.0
CD40
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	0.3
Macrophages rest	0.0	Lung	0.0
Macrophages LPS	0.0	Thymus	0.0
HUVEC none	0.0	Kidney	0.0
HUVEC starved	0.0

[0598] CNS_neurodegeneration_v1.0 Summary: Ag3701 Expression of the CG90021-01 gene is low/undetectable in all samples on this panel (CTs>35).

[0599] General_screening_panel_v1.4 Summary: Ag3701 Expression of the CG90021-01 gene is restricted to the testis (CT=33). This expression agrees with the charactizeration of this protein as a putative testicular protein. Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker for testicular tissue. Furthermore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of male infertility and hypogonadism.

[0600] Panel 4.1D Summary: Ag3701 Expression of the CG90021-01 gene is restricted to a sample of activated secondary Th1 cells (CT=30.4). Thus, expression of this gene could be used to distinguish this sample from other samples on this panel and as a marker to identify activated Th1 cells. Furthermore, this gene product may be involved in diseases where T cells are chronically stimulated.

[0601] I. NOV9a (CG90709-01: Ion Transport Protein)

[0602] Expression of gene CG90709-01 was assessed using the primer-probe set Ag3712, described in Table IA.

TABLE IA
Probe Name Ag3712
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-gttacacattctgtggctggat-3′	22	1217	132
Probe	TET-5′-tgtcttaggaccataccatctacagtttga-3′-	30	1239	133
	TAMRA
Reverse	5′-acactcagcaactgtgttcaga-3′	22	1272	134

[0603] CNS_neurodegeneration_v1.0 Summary: Ag3712 Expression of the CG90709-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0604] General_screening_panel_v1.4 Summary: Ag3712 Results from one experiment with the CG90709-01 gene are not included. The amp plot indicates that there were experimental difficulties with this run.

[0605] Panel 4.1D Summary: Ag3712 Expression of the CG90709-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0606] J. NOV9c and NOV9d (CG90709-03 and CG90709-04: Ion Transport Protein)

[0607] Expression of gene CG90709-03 and CG90709-04 was assessed using the primer-probe sets Ag5864 and Ag5941, described in Tables JA and JB. Results of the RTQ-PCR runs are shown in Tables JC, JD, JE and JF.

TABLE JA
Probe Name Ag5864
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-gaaagagtcctcagccttcct-3′	21	1712	135
Probe	TET-5′-cacttcttttcctcctccgacagcag-3′-	26	1742	136
	TAMRA
Reverse	5′-tagcagaactttagctaataggtatcaagt-3′	30	1774	137

[0608]

TABLE JB
Probe Name Ag5941
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-gagagaggatcaggtgttttcag-3′	23	135	138
Probe	TET-5′-taaccgtcagaaatgcaatggcacat-3′-	26	160	139
	TAMRA
Reverse	5′-cttagacattcttctttcatctcagaat-3′	28	190	140

[0609]

TABLE JC
AI comprehensive panel-v1.0
	Rel. Exp.(%)	Rel. Exp.(%)		Rel. Exp.(%)	Rel. Exp.(%)
	Ag5864, Run	Ag5941, Run		Ag5864, Run	Ag5941, Run
Tissue Name	247947740	247756614	Tissue Name	247947740	247756614
110967 COPD-F	0.6	0.0	112427 Match	12.8	10.0
			Control
			Psoriasis-F
110980 COPD-F	0.3	0.5	112418	0.0	0.3
			Psoriasis-M
110968 COPD-M	0.0	0.5	112723 Match	0.0	0.0
			Control
			Psoriasis-M
110977 COPD-M	4.0	2.1	112419	0.9	0.0
			Psoriasis-M
110989	36.3	21.6	112424 Match	1.3	0.0
Emphysema-F			Control
			Psoriasis-M
110992	4.9	4.6	112420	11.9	7.4
Emphysema-F			Psoriasis-M
110993	2.5	0.5	112425 Match	3.5	10.4
Emphysema-F			Control
			Psoriasis-M
110994	1.0	1.7	104689 (MF)	23.3	15.9
Emphysema-F			OA Bone-
			Backus
110995	11.6	9.2	104690 (MF)	11.3	10.0
Emphysema-F			Adj “Normal”
			Bone-Backus
110996	0.4	1.6	104691 (MF)	11.5	8.8
Emphysema-F			OA Synovium-
			Backus
110997	5.5	1 .4	104692 (BA)	80.7	100.0
Asthma-M			OA Cartilage-
			Backus
111001	2.5	0.7	104694 (BA)	5.8	3.9
Asthma-F			OA Bone-
			Backus
111002	3.3	1.5	104695 (BA)	27.2	19.8
Asthma-F			Adj “Normal”
			Bone-Backus
111003 Atopic	7.0	4.2	104696 (BA)	5.0	6.9
Asthma-F			OA Synovium-
			Backus
111004 Atopic	10.9	7.4	104700 (SS)	10.8	2.6
Asthma-F			OA Bone-
			Backus
111005 Atopic	7.9	5.8	104701 (SS)	22.2	19.3
Asthma-F			Adj “Normal”
			Bone-Backus
111006 Atopic	0.0	0.9	104702 (SS)	11.5	8.5
Asthma-F			OA Synovium-
			Backus
111417	2.7	2.3	117093 OA	2.9	4.2
Allergy-M			Cartilage Rep7
112347	0.0	0.2	112672 OA	4.2	1.5
Allergy-M			Bone5
112349 Normal	0.0	0.0	112673 OA	1.9	1.1
Lung-F			Synovium5
112357 Normal	4.5	2.2	112674 OA	3.3	1.0
Lung-F			Synovial Fluid
			cells5
112354 Normal	1.0	0.8	117100 OA	0.5	0.7
Lung-M			Cartilage
			Rep14
112374	2.2	0.0	112756 OA	0.8	0.5
Crohns-F			Bone9
112389 Match	2.8	2.3	112757 OA	0.6	0.0
Control			Synovium9
Crohns-F
112375	1.9	0.6	112758 OA	1.5	0.3
Crohns-F			Synovial Fluid
			Cells9
112732 Match	59.9	36.1	117125 RA	0.0	0.5
Control			Cartilage Rep2
Crohns-F
112725	0.0	0.0	113492 Bone2	27.4	11 .8
Crohns-M			RA
112387 Match	5.0	4.4	113493	9.9	4.1
Control			Synovium2
Crohns-M			RA
112378	0.4	0.0	113494 Syn	12.7	7.5
Crohns-M			Fluid Cells RA
112390 Match	23.3	15.8	113499	27.0	8.7
Control			Cartilage4 RA
Crohns-M
112726	3.7	2.0	113500 Bone4	31.2	15.9
Crohns-M			RA
112731 Match	4.9	2.1	113501	24.5	10.4
Control			Synovium4
Crohns-M			RA
112380 Ulcer	10.1	8.8	113502 Syn	20.4	6.4
Col-F			Fluid Cells4
			RA
112734 Match	100.0	61.1	113495	21.2	9.7
Control Ulcer			Cartilage3 RA
Col-F
112384 Ulcer	9.2	7.0	113496 Bone3	16.4	9.7
Col-F			RA
112737 Match	2.7	0.8	113497	7.4	5.6
Control Ulcer			Synovium3
Col-F			RA
112386 Ulcer	0.3	0.0	113498 Syn	26.6	15.8
Col-F			Fluid Cells3
			RA
112738 Match	16.0	5.3	117106	0.0	0.3
Control Ulcer			Normal
Col-F			Cartilage
			Rep20
112381 Ulcer	0.5	0.6	113663 Bone3	0.0	0.3
Col-M			Normal
112735 Match	1.3	0.7	113664	0.0	0.0
Control Ulcer			Synovium3
Col-M			Normal
112382 Ulcer	6.7	2.3	113665 Syn	0.7	0.3
Col-M			Fluid Cells3
			Normal
112394 Match	0.0	0.5	117107	0.6	0.7
Control Ulcer			Normal
Col-M			Cartilage
			Rep22
112383 Ulcer	6.4	4.2	113667 Bone4	0.9	1.8
Col-M			Normal
112736 Match	1.6	0.6	113668	2.3	1.9
Control Ulcer			Synovium4
Col-M			Normal
112423	1.3	1.8	113669 Syn	6.7	1.7
Psoriasis-F			Fluid Cells4
			Normal

[0610]

TABLE JD
CNS_neurodegeneration_v1.0
	Rel. Exp.(%) Ag5864,		Rel. Exp.(%) Ag5864,
Tissue Name	Run 247189534	Tissue Name	Run 247189534
AD 1 Hippo	17.6	Control (Path) 3	0.0
		Temporal Ctx
AD 2 Hippo	100.0	Control (Path) 4	17.0
		Temporal Ctx
AD 3 Hippo	0.0	AD 1 Occipital Ctx	0.0
AD 4 Hippo	87.1	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	25.9	AD 3 Occipital Ctx	0.0
AD 6 Hippo	80.1	AD 4 Occipital Ctx	17.7
Control 2 Hippo	6.2	AD 5 Occipital Ctx	17.4
Control 4 Hippo	47.3	AD 6 Occipital Ctx	0.0
Control (Path) 3	17.4	Control 1 Occipital	13.7
Hippo		Ctx
AD 1 Temporal Ctx	0.0	Control 2 Occipital	16.6
		Ctx
AD 2 Temporal Ctx	29.3	Control 3 Occipital	41.5
		Ctx
AD 3 Temporal Ctx	33.7	Control 4 Occipital	0.0
		Ctx
AD 4 Temporal Ctx	12.2	Control (Path) 1	43.8
		Occipital Ctx
AD 5 Inf Temporal	32.8	Control (Path) 2	16.4
Ctx		Occipital Ctx
AD 5 Sup	56.3	Control (Path) 3	0.0
Temporal Ctx		Occipital Ctx
AD 6 Inf Temporal	15.2	Control (Path) 4	24.5
Ctx		Occipital Ctx
AD 6 Sup	66.4	Control 1 Parietal	27.4
Temporal Ctx		Ctx
Control 1 Temporal	0.0	Control 2 Parietal	61.1
Ctx		Ctx
Control 2 Temporal	0.0	Control 3 Parietal	0.0
Ctx		Ctx
Control 3 Temporal	15.9	Control (Path) 1	19.2
Ctx		Parietal Ctx
Control 3 Temporal	43.8	Control (Path) 2	14.7
Ctx		Parietal Ctx
Control (Path) 1	12.3	Control (Path) 3	0.0
Temporal Ctx		Parietal Ctx
Control (Path) 2	13.4	Control (Path) 4	43.8
Temporal Ctx		Parietal Ctx

[0611]

TABLE JE
General_screening_panel_v1.5
	Rel. Exp.(%) Ag5864,		Rel. Exp.(%) Ag5864,
Tissue Name	Run 246287340	Tissue Name	Run 246287340
Adipose	9.0	Renal ca. TK-10	77.9
Melanoma*	0.2	Bladder	21.3
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	48.6	Gastric ca. KATO III	0.0
Melanoma*	37.1	Colon ca. SW-948	0.0
LOXIMVI
Melanoma* SK-	100.0	Colon ca. SW480	97.3
MEL-5
Squamous cell	17.9	Colon ca.* (SW480	0.0
carcinoma SCC-4		met) SW620
Testis Pool	6.8	Colon ca. HT29	0.5
Prostate ca.* (bone	14.3	Colon ca. HCT-116	72.7
met) PC-3
Prostate Pool	7.7	Colon ca. CaCo-2	1.7
Placenta	0.4	Colon cancer tissue	27.9
Uterus Pool	2.3	Colon ca. SW1116	22.1
Ovarian ca.	2.4	Colon ca. Colo-205	0.4
OVCAR-3
Ovarian ca. SK-OV-3	13.4	Colon ca. SW-48	14.5
Ovarian ca.	0.7	Colon Pool	1.7
OVCAR-4
Ovarian ca.	19.3	Small Intestine Pool	9.9
OVCAR-5
Ovarian ca. IGROV-1	11.3	Stomach Pool	6.0
Ovarian ca.	13.6	Bone Marrow Pool	4.1
OVCAR-8
Ovary	0.0	Fetal Heart	0.9
Breast ca. MCF-7	20.6	Heart Pool	0.6
Breast ca. MDA-	12.3	Lymph Node Pool	6.8
MB-231
Breast ca. BT 549	5.9	Fetal Skeletal Muscle	0.5
Breast ca. T47D	10.4	Skeletal Muscle Pool	1.2
Breast ca. MDA-N	56.6	Spleen Pool	48.3
Breast Pool	1.7	Thymus Pool	18.8
Trachea	10.3	CNS cancer (glio/astro)	13.7
		U87-MG
Lung	0.3	CNS cancer (glio/astro)	0.0
		U-118-MG
Fetal Lung	15.9	CNS cancer	0.0
		(neuro; met) SK-N-AS
Lung ca. NCI-N417	0.5	CNS cancer (astro) SF-	1.9
		539
Lung ca. LX-1	0.0	CNS cancer (astro)	5.3
		SNB-75
Lung ca. NCI-H146	0.0	CNS cancer (glio)	6.9
		SNB-19
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-	77.9
		295
Lung ca. A549	12.2	Brain (Amygdala) Pool	0.5
Lung ca. NCI-H526	14.8	Brain (cerebellum)	0.0
Lung ca. NCI-H23	33.4	Brain (fetal)	0.0
Lung ca. NCI-H460	17.7	Brain (Hippocampus)	0.2
		Pool
Lung ca. HOP-62	0.7	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	2.5	Brain (Substantia nigra)	0.0
		Pool
Liver	0.0	Brain (Thalamus) Pool	0.7
Fetal Liver	1.0	Brain (whole)	0.2
Liver ca. HepG2	0.0	Spinal Cord Pool	3.1
Kidney Pool	2.5	Adrenal Gland	28.9
Fetal Kidney	2.3	Pituitary gland Pool	0.7
Renal ca. 786-0	27.9	Salivary Gland	1.8
Renal ca. A498	5.0	Thyroid (female)	0.3
Renal ca. ACHN	5.8	Pancreatic ca.	0.0
		CAPAN2
Renal ca. UO-31	12.6	Pancreas Pool	6.9

[0612]

TABLE JF
Panel 4.1D
	Rel.	Rel.		Rel.	Rel.
	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)
	Ag5864,	Ag5941,		Ag5864,	Ag5941,
	Run	Run		Run	Run
Tissue Name	246733832	247582900	Tissue Name	246733832	247582900
Secondary Th1 act	21.9	39.2	HUVEC IL-1beta	0.0	0.0
Secondary Th2 act	43.2	61.6	HUVEC IFN	0.0	0.0
			gamma
Secondary Tr1 act	5.6	9.2	HUVEC TNF	0.0	0.0
			alpha + IFN
			gamma
Secondary Th1 rest	0.1	0.8	HUVEC TNF	0.0	0.0
			alpha + IL4
Secondary Th2 rest	0.2	0.0	HUVEC IL-11	0.0	0.0
Secondary Tr1 rest	0.1	0.0	Lung	0.0	0.0
			Microvascular EC
			none
Primary Th1 act	0.3	0.5	Lung	0.0	0.0
			Microvascular EC
			TNF alpha + IL-
			1beta
Primary Th2 act	2.0	2.4	Microvascular	0.0	0.0
			Dermal EC none
Primary Tr1 act	5.1	10.2	Microsvasular	0.0	0.0
			Dermal EC
			TNF alpha + IL-
			1beta
Primary Th1 rest	0.1	0.0	Bronchial	0.3	0.5
			epithelium
			TNF alpha +
			IL1beta
Primary Th2 rest	0.3	0.4	Small airway	0.2	0.4
			epithelium none
Primary Tr1 rest	0.0	0.2	Small airway	0.4	0.7
			epithelium
			TNF alpha + IL-
			1beta
CD45RA CD4	8.5	18.2	Coronery artery	0.0	0.0
lymphocyte act			SMC rest
CD45RO CD4	12.2	30.4	Coronery artery	0.0	0.0
lymphocyte act			SMC TNF
			alpha + IL-1beta
CD8 lymphocyte	3.1	5.8	Astrocytes rest	0.1	0.0
act
Secondary CD8	11.5	23.8	Astrocytes	0.1	0.0
lymphocyte rest			TNF alpha + IL-
			1beta
Secondary CD8	2.7	6.6	KU-812	0.0	0.0
lymphocyte act			(Basophil) rest
CD4 lymphocyte	0.1	0.3	KU-812	0.0	0.0
none			(Basophil)
			PMA/ionomycin
2ry	0.7	0.5	CCD1106	0.3	0.0
Th1/Th2/Tr1-anti-			(Keratinocytes)
CD95 CH11			none
LAK cells rest	2.9	6.2	CCD1106	0.2	0.2
			(Keratinocytes)
			TNF alpha + IL-
			1beta
LAK cells IL-2	2.9	7.7	Liver cirrhosis	0.4	1.9
LAK cells	0.7	1.2	NCI-H292 none	2.1	3.7
IL-2 + IL-12
LAK cells	3.8	7.4	NCI-H292 IL-4	2.5	5.4
IL-2 + IFN gamma
LAK cells IL-2 +	1.3	4.6	NCI-H292 IL-9	2.9	4.5
IL-18
LAK cells	8.8	18.6	NCI-H292 IL-13	3.0	3.2
PMA/ionomycin
NK Cells IL-2 rest	14.0	21.9	NCI-H292 IFN	1.2	2.0
			gamma
Two Way MLR 3	3.4	6.1	HPAEC none	0.0	0.0
day
Two Way MLR 5	0.6	1.0	HPAEC TNF	0.0	0.0
day			alpha + IL-1 beta
Two Way MLR 7	2.8	4.6	Lung fibroblast	0.2	0.6
day			none
PBMC rest	0.3	0.3	Lung fibroblast	0.2	0.6
			TNF alpha + IL-1
			beta
PBMC PWM	2.7	5.0	Lung fibroblast	0.3	0.3
			IL-4
PBMC PHA-L	2.7	2.8	Lung fibroblast	0.3	0.6
			IL-9
Ramos (B cell)	2.1	4.6	Lung fibroblast	0.3	0.4
none			IL-13
Ramos (B cell)	22.5	52.5	Lung fibroblast	0.4	1.0
ionomycin			IFN gamma
B lymphocytes	11.3	33.0	Dermal fibroblast	0.8	1.7
PWM			CCD1070 rest
B lymphocytes	15.9	37.1	Dermal fibroblast	5.8	12.5
CD40L and IL-4			CCD1070 TNF
			alpha
EOL-1 dbcAMP	0.9	3.4	Dermal fibroblast	0.5	0.4
			CCD1070 IL-1
			beta
EOL-1 dbcAMP	0.1	0.0	Dermal fibroblast	0.1	0.1
PMA/ionomycin			IFN gamma
Dendritic cells	2.0	3.1	Dermal fibroblast	0.0	0.5
none			IL-4
Dendritic cells LPS	10.6	12.2	Dermal	0.1	0.0
			Fibroblasts rest
Dendritic cells anti-	0.5	0.9	Neutrophils	0.2	0.3
CD40			TNFa + LPS
Monocytes rest	0.1	0.0	Neutrophils rest	0.0	0.1
Monocytes LPS	100.0	100.0	Colon	0.2	0.2
Macrophages rest	0.8	1.1	Lung	0.4	0.2
Macrophages LPS	9.7	9.8	Thymus	0.3	0.9
HUVEC none	0.0	0.0	Kidney	05	0.8
HUVEC starved	0.0	0.0

[0613] AI_comprehensive panel_v1.0 Summary: Ag5864 Two experiments with different probe and primer sets are in excellent agreements with highest expression of the CG90709-03 gene in matched control ulcerative colitis sample and OA cartilage (CTs=30). Interestingly, expression of this gene is higher in matched control ulcerative colitis and Crohn's sample as compared the sample of corresponding diseased tissue. In addition, significant expression of this gene is also observed in synovium, bone and cartilage samples derived from orthoarthritis and rheumatoid arthritis patient. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of inflammatory bowel diseases and arthritis.

[0614] CNS_neurodegeneration_v1.0 Summary: Ag5864 Expression of the CG90709-03 gene is low/undetectable (CTs >34) across all of the samples on this panel.

[0615] General_screening_panel_v1.5 Summary: Ag5864 Highest expression of the CG90709-03 gene is detected in melanoma SK-MEL-5 cell line (CT=28.2). High to moderate expression of this gene is also seen in melanoma, renal cancer, squamous cell carcinoma, ovarian and breast cancer, colon cancer and CNS cancer cell lines. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, or antibodies, might be beneficial in the treatment of these cancers.

[0616] Among tissues with metabolic or endocrine function, this gene is expressed at moderate levels in pancreas, adipose, adrenal gland, 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.

[0617] The CG90709-03 gene codes for an ion transport protein. Ion transport proteins are responsible for the movement of cations through the membrane. This family contains sodium, potassium and calcium ion channels. The physiologic function of an ion transport protein is determined, in part, by its subcellular localization and by the cellular mechanisms that modulate its activity (Ref.1). Recently, mutations of a gene encoding an ion transport protein, has been shown to be involved in the development of chronic pancreatitis including cystic fibrosis of the pancrease (Ref.2). The CG90709-03 gene is expressed in pancrease at a moderate levels (CT=33). Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of pancreatitis.

[0618] In addition, significant expression of this gene is also observed in spleen and thymus. Therefore, antibodies or small molecule therapeutics that block the function of this gene product may be useful as anti-inflammatory therapeutics for the treatment of allergies, autoimmune diseases, and inflammatory diseases.

[0619] See, generally,

[0620] Dunbar L A, Caplan M J. (2001) Ion pumps in polarized cells: sorting and regulation of the Na+, K+− and H+, K+−ATPases. J Biol Chem Aug. 10, 2001;276(32):29617-20. PMID: 11404365

[0621] Bornstein J D, Cohn J A. (1 999) Cystic fibrosis in the pancreas: recent advances provide new insights. Curr Gastroenterol Rep 1(2):161-5. PMID: 10980944

[0622] Panel 4.1D Summary: Ag5864 Highest expression of the CG90709-03 gene is detected in LPS treated monocytes (CT=27). In addition, expression of this gene is low or undectable in resting monocytes (CT=37). Therefore, expression of this gene can be used to distinguish between the treated and resting monocytes. Furthermore, the expression of this gene 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. Therefore, modulation of the expression or activity of this gene through the application of monoclonal antibodies or small molecule 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.

[0623] Expression of this gene is stimulated in activated primary and secondary Th1, Th2 and Tr1 cells, TNF alpha treated Dermal fibroblast CCD1070 cells, LPS treated macrophages, ionomycin treated Ramos B cells, PWM/CD40L and IL-4 treated B lymphocytes, and PWM/PHA treated PMBC. Therefore, the putative protein encoded by this gene could potentially be used diagnostically to identify activated B or T cells. In addition, the gene product could also potentially be used therapeutically in the treatment of asthma, emphysema, IBD, lupus or arthritis and in other diseases in which T cells and B cells are activated.

[0624] Expression of this gene is also stimulated in TNF alpha treated dermal fibroblast CCD1070 (CT=31) as compared to the resting cells (CT=34). Therefore, expression of this gene can be used to distinguish between these treated and resting fibroblast cells. Also, therapeutic modulation of this gene product could be useful in the treatment of skin disorder such as psoriasis.

[0625] K. NOV10a (CG90739-01: Neuronal thread protein like)

[0626] Expression of gene CG90739-01 was assessed using the primer-probe set Ag3796, described in Table KA. Results of the RTQ-PCR runs are shown in Tables KB, KC, and KD.

TABLE KA
Probe Name Ag3796
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-aatttgtgtccgaagtgcag-3′	20	465	141
Probe	TET-5′-tggcagtaacctcaagcttcgaaggt-3′-	26	514	142
	TAMRA
Reverse	5′-tatggatctgcaggcatctc-3′	20	542	143

[0627]

TABLE KB
CNS_neurodegeneration_v1.0
	Rel. Exp.(%) Ag3796,		Rel. Exp.(%) Ag3796,
Tissue Name	Run 211176632	Tissue Name	Run 211176632
AD 1 Hippo	0.0	Control (Path) 3	19.9
		Temporal Ctx
AD 2 Hippo	0.0	Control (Path) 4	11.6
		Temporal Ctx
AD 3 Hippo	0.0	AD 1 Occipital Ctx	0.0
AD 4 Hippo	0.0	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	100.0	AD 3 Occipital Ctx	0.0
AD 6 Hippo	53.6	AD 4 Occipital Ctx	7.9
Control 2 Hippo	31.2	AD 5 Occipital Ctx	33.7
Control 4 Hippo	10.3	AD 6 Occipital Ctx	41.8
Control (Path) 3	0.0	Control 1 Occipital	0.0
Hippo		Ctx
AD 1 Temporal Ctx	3.7	Control 2 Occipital	55.5
		Ctx
AD 2 Temporal Ctx	5.5	Control 3 Occipital	11.0
		Ctx
AD 3 Temporal Ctx	7.2	Control 4 Occipital	0.0
		Ctx
AD 4 Temporal Ctx	0.0	Control (Path) 1	18.9
		Occipital Ctx
AD 5 Inf Temporal	82.4	Control (Path) 2	23.2
Ctx		Occipital Ctx
AD 5 Sup Temporal	12.0	Control (Path) 3	1.5
Ctx		Occipital Ctx
AD 6 Inf Temporal	77.9	Control (Path) 4	0.0
Ctx		Occipital Ctx
AD 6 Sup Temporal	58.2	Control 1 Parietal	0.0
Ctx		Ctx
Control 1 Temporal	0.0	Control 2 Parietal	1.9
Ctx		Ctx
Control 2 Temporal	47.3	Control 3 Parietal	0.0
Ctx		Ctx
Control 3 Temporal	9.7	Control (Path) 1	25.9
Ctx		Parietal Ctx
Control 4 Temporal	0.0	Control (Path) 2	18.3
Ctx		Parietal Ctx
Control (Path) 1	46.0	Control (Path) 3	7.0
Temporal Ctx		Parietal Ctx
Control (Path) 2	32.1	Control (Path) 4	7.6
Temporal Ctx		Parietal Ctx

[0628]

TABLE KC
General_screening_panel_v1.5
	Rel. Exp.(%) Ag3796,		Rel. Exp.(%) Ag3796,
Tissue Name	Run 258082161	Tissue Name	Run 258082161
Adipose	0.2	Renal ca. TK-10	0.4
Melanoma*	0.3	Bladder	2.3
Hs688(A).T
Melanoma*	0.5	Gastric ca. (liver met.)	4.8
Hs688(B).T		NCI-N87
Melanoma* M14	2.5	Gastric ca. KATO III	5.0
Melanoma*	0.6	Colon ca. SW-948	0.2
LOXIMVI
Melanoma* SK-	1.0	Colon ca. SW480	0.2
MEL-5
Squamous cell	0.1	Colon ca.* (SW480	0.6
carcinoma SCC-4		met) SW620
Testis Pool	100.0	Colon ca. HT29	0.2
Prostate ca.* (bone	0.7	Colon ca. HCT-116	1.8
met) PC-3
Prostate Pool	0.3	Colon ca. CaCo-2	1.2
Placenta	0.1	Colon cancer tissue	0.7
Uterus Pool	0.4	Colon ca. SW1116	0.0
Ovarian ca.	1.1	Colon ca. Colo-205	0.4
OVCAR-3
Ovarian ca. SK-OV-3	3.7	Colon ca. SW-48	0.0
Ovarian ca.	0.2	Colon Pool	0.9
OVCAR-4
Ovarian ca.	1.9	Small Intestine Pool	0.6
OVCAR-5
Ovarian ca. IGROV-1	0.1	Stomach Pool	0.6
Ovarian ca.	0.1	Bone Marrow Pool	0.5
OVCAR-8
Ovary	0.2	Fetal Heart	0.4
Breast ca. MCF-7	1.7	Heart Pool	0.6
Breast ca. MDA-	1.1	Lymph Node Pool	0.8
MB-231
Breast ca. BT 549	0.3	Fetal Skeletal Muscle	0.5
Breast ca. T47D	1.1	Skeletal Muscle Pool	0.4
Breast ca. MDA-N	0.4	Spleen Pool	1.1
Breast Pool	0.0	Thymus Pool	0.8
Trachea	0.2	CNS cancer (glio/astro)	1.5
		U87-MG
Lung	0.7	CNS cancer (glio/astro)	0.4
		U-118-MG
Fetal Lung	0.6	CNS cancer	0.2
		(neuro; met) SK-N-AS
Lung ca. NCI-N417	0.3	CNS cancer (astro) SF-	0.1
		539
Lung ca. LX-1	0.1	CNS cancer (astro)	0.9
		SNB-75
Lung ca. NCI-H146	0.0	CNS cancer (glio)	0.7
		SNB-19
Lung ca. SHP-77	0.8	CNS cancer (glio) SF-	1.8
		295
Lung ca. A549	3.3	Brain (Amygdala) Pool	0.3
Lung ca. NCI-H526	1.0	Brain (cerebellum)	0.7
Lung ca. NCI-H23	2.4	Brain (fetal)	0.6
Lung ca. NCI-H460	0.8	Brain (Hippocampus)	0.8
		Pool
Lung ca. HOP-62	0.1	Cerebral Cortex Pool	1.2
Lung ca. NCI-H522	0.6	Brain (Substantia nigra)	0.3
		Pool
Liver	0.0	Brain (Thalamus) Pool	1.2
Fetal Liver	0.6	Brain (whole)	0.2
Liver ca. HepG2	1.0	Spinal Cord Pool	0.8
Kidney Pool	0.6	Adrenal Gland	0.2
Fetal Kidney	0.6	Pituitary gland Pool	0.3
Renal ca. 786-0	1.2	Salivary Gland	0.3
Renal ca. A498	0.0	Thyroid (female)	0.2
Renal ca. ACHN	0.0	Pancreatic ca.	0.4
		CAPAN2
Renal ca. UO-31	1.4	Pancreas Pool	0.5

[0629]

TABLE KD
Panel 4.1D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag3796, Run		Ag3796, Run
Tissue Name	169997344	Tissue Name	169997344
Secondary Th1 act	83.5	HUVEC IL-1beta	4.9
Secondary Th2 act	30.8	HUVEC IFN gamma	0.0
Secondary Tr1 act	74.7	HUVEC TNF alpha + IFN	4.9
		gamma
Secondary Th1 rest	13.4	HUVEC TNF alpha + IL4	12.1
Secondary Th2 rest	42.9	HUVEC IL-11	5.9
Secondary Tr1 rest	37.1	Lung Microvascular EC	0.0
		none
Primary Th1 act	28.1	Lung Microvascular EC	0.0
		TNF alpha + IL-1beta
Primary Th2 act	21.5	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	11.3	Microsvasular Dermal EC	2.2
		TNF alpha + IL-1beta
Primary Th1 rest	42.6	Bronchial epithelium	0.0
		TNF alpha + IL1beta
Primary Th2 rest	55.9	Small airway epithelium	6.5
		none
Primary Tr1 rest	33.2	Small airway epithelium	8.4
		TNF alpha + IL-1beta
CD45RA CD4	26.4	Coronery artery SMC rest	4.7
lymphocyte act
CD45RO CD4	40.9	Coronery artery SMC	0.0
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	55.5	Astrocytes rest	0.0
Secondary CD8	17.1	Astrocytes TNF alpha +	2.9
lymphocyte rest		IL-1beta
Secondary CD8	26.4	KU-812 (Basophil) rest	17.1
lymphocyte act
CD4 lymphocyte none	9.5	KU-812 (Basophil)	10.4
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	100.0	CCD1106 (Keratinocytes)	7.2
CD95 CH11		none
LAK cells rest	12.0	CCD1106 (Keratinocytes)	7.8
		TNF alpha + IL-1beta
LAK cells IL-2	49.3	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	20.7	NCI-H292 none	1.8
LAK cells IL-2 + IFN	36.6	NCI-H292 IL-4	0.0
gamma
LAK cells IL-2 + IL-18	14.7	NCI-H292 IL-9	3.3
LAK cells	10.8	NCI-H292 IL-13	4.9
PMA/ionomycin
NK Cells IL-2 rest	37.1	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	19.2	HPAEC none	0.0
Two Way MLR 5 day	18.4	HPAEC TNF alpha + IL-1	0.0
		beta
Two Way MLR 7 day	24.0	Lung fibroblast none	3.3
PBMC rest	4.9	Lung fibroblast TNF	9.6
		alpha + IL-1beta
PBMC PWM	15.0	Lung fibroblast IL-4	3.1
PBMC PHA-L	27.4	Lung fibroblast IL-9	4.2
Ramos (B cell) none	4.1	Lung fibroblast IL-13	12.9
Ramos (B cell)	5.5	Lung fibroblast IFN	0.0
ionomycin		gamma
B lymphocytes PWM	31.4	Dermal fibroblast	2.3
		CCD1070 rest
B lymphocytes CD40L	31.2	Dermal fibroblast	27.2
and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	10.4	Dermal fibroblast	0.0
		CCD1070 IL-1beta
EOL-1 dbcAMP	55.5	Dermal fibroblast IFN	0.0
PMA/ionomycin		gamma
Dendritic cells none	65.5	Dermal fibroblast IL-4	14.9
Dendritic cells LPS	39.0	Dermal Fibroblasts rest	0.5
Dendritic cells anti-	33.9	Neutrophils TNFa + LPS	11.5
CD40
Monocytes rest	15.9	Neutrophils rest	62.0
Monocytes LPS	17.6	Colon	9.1
Macrophages rest	16.5	Lung	2.6
Macrophages LPS	13.1	Thymus	23.5
HUVEC none	0.0	Kidney	5.3
HUVEC starved	4.9

[0630] CNS_neurodegeneration_v1.0 Summary: Ag3796 This panel does not show differential expression of the CG56153-01 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain, with highest expression in the hippocampus of an Alzheimer's patient (CT=33). 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.

[0631] General_screening_panel_v1.4 Summary: Ag3796 Results from one experiment with the CG90739-01 gene are not included. The amp plot indicates that there were experimental difficulties with this run.

[0632] General_screening_panel_v1.5 Summary: Ag3796 Highest expression of the CG90739-01 gene is seen in the testis (CT=27). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker of testicular tissue. Furthermore, therapeutic modulation of the expression or function of this protein may be effective in the treatment of male infertility or hypogonadism.

[0633] In addition, low but significant expression of this gene is seen in many regions of the central nervous system examined, including hippocampus, thalamus, cerebellum, cerebral cortex, and spinal cord. This gene codes for variant of neuronal thread protein-like protein. Neuronal thread protein is a thread protein identified in AD and Down's syndrome brain tissue. The AD-associated neuronal thread protein (AD7c-NTP), a ˜41 kD membrane-spanning phosphoprotein, is shown to causes apoptosis and neuritic sprouting in transfected neuronal cells (Ref. 1, 2). 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, and Downs syndrome.

[0634] See, generally,

[0635] de la Monte SM. (1999) Molecular abnormalities of the brain in Down syndrome: relevance to Alzheimer's neurodegeneration. J Neural Transm Suppl;57:1-19. PMID: 10666665

[0636] Suzanne M. de la Monte, Jack R. Wands (2001) The AD7C-NTP neuronal thread protein biomarker for detecting Alzheimer's disease. Journal of Alzheimer's Disease Volume 3 (3), 345-353.

[0637] Oncology_cell_line_screening_panel_v3.2 Summary: Ag3796 Expression of the CG90739-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0638] Panel 4.1D Summary: Ag3796 Expression of the CG90739-01 gene is highest in secondary Th1/TH2/Tr1 cells treated with anti-CD95 (CT=31.7). Expression of this gene in this panel appears to be mainly associated with hematopoictic cells, including T cells, particularly chronically activated Th1, Th2 and Tr1 cells, LAK cells, macrophages and dendritic cells. Thus, this transcript or the protein it encodes could be used to detect hematopoietically-derived cells. Furthermore, therapeutics designed with the protein encoded by this transcript could be important in the regulation the function of antigen presenting cells (macrophages and dendritic cells)or T cells and be important in the treatment of asthma, emphysema, psoriasis, arthrtis, and IBD.

[0639] L. NOV11a and NOV11b (CG91667-01 and CG91667-02: dik1)

[0640] Expression of gene CG91667-01 and CG91667-02 was assessed using the primer-probe set Ag3009, described in Table LA. Results of the RTQ-PCR runs are shown in Tables LB, LC, LD, LE and LF. Please note that CG91667-02 represents a full-length physical clone of the CG91667-01 gene, validating the prediction of the gene sequence.

TABLE LA
Probe Name Ag3009
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-gggtatcgtcttcctcaacaag-3′	22	966	144
Probe	TET-5′-ctacaaccacatgctgcggaagaaga-3′-	26	1014	145
	TAMRA
Reverse	5′-ttgtactgaagcagcaggttct-3′	22	1040	146

[0641]

TABLE LB
AI_comprehensive panel_v1.0
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag3009, Run		Ag3009, Run
Tissue Name	228157490	Tissue Name	228157490
110967 COPD-F	0.1	112427 Match Control	0.8
		Psoriasis-F
110980 COPD-F	0.0	112418 Psoriasis-M	0.1
110968 COPD-M	0.1	112723 Match Control	0.0
		Psoriasis-M
110977 COPD-M	0.0	112419 Psoriasis-M	0.1
110989 Emphysema-F	1.1	112424 Match Control	0.0
		Psoriasis-M
110992 Emphysema-F	0.3	112420 Psoriasis-M	0.8
110993 Emphysema-F	0.0	112425 Match Control	0.6
		Psoriasis-M
110994 Emphysema-F	0.0	104689 (MF) OA	0.0
		Bone-Backus
110995 Emphysema-F	1.0	104690 (MF) Adj	0.0
		“Normal” Bone-Backus
110996 Emphysema-F	0.1	104691 (MF) OA	0.0
		Synovium-Backus
110997 Asthma-M	0.0	104692 (BA) OA	0.0
		Cartilage-Backus
111001 Asthma-F	0.0	104694 (BA) OA	0.0
		Bone-Backus
111002 Asthma-F	0.0	104695 (BA) Adj	0.0
		“Normal” Bone-Backus
111003 Atopic	0.0	104696 (BA) OA	0.0
Asthma-F		Synovium-Backus
111004 Atopic	0.1	104700 (SS) OA Bone-	0.0
Asthma-F		Backus
111005 Atopic	0.0	104701 (SS) Adj	0.0
Asthma-F		“Normal” Bone-Backus
111006 Atopic	0.1	104702 (SS) OA	0.0
Asthma-F		Synovium-Backus
111417 Allergy-M	0.0	117093 OA Cartilage	0.2
		Rep7
112347 Allergy-M	1.6	112672 OA Bone5	0.0
112349 Normal	1.8	112673 OA	0.0
Lung-F		Synovium5
112357 Normal	19.8	112674 OA Synovial	0.0
Lung-F		Fluid cells5
112354 Normal	37.4	117100 OA Cartilage	0.2
Lung-M		Rep14
112374 Crohns-F	0.8	112756 OA Bone9	100.0
112389 Match	0.0	112757 OA	1.9
Control Crohns-F		Synovium9
112375 Crohns-F	2.2	112758 OA Synovial	0.0
		Fluid Cells9
112732 Match	0.0	117125 RA Cartilage	0.1
Control Crohns-F		Rep2
112725 Crohns-M	11.9	113492 Bone2 RA	0.4
112387 Match	0.0	113493 Synovium2 RA	0.1
Control Crohns-M
112378 Crohns-M	5.1	113494 Syn Fluid Cells	0.2
		RA
112390 Match	0.1	113499 Cartilage4 RA	0.1
Control Crohns-M
112726 Crohns-M	0.1	113500 Bone4 RA	0.1
112731 Match	1.8	113501 Synovium4 RA	0.1
Control Crohns-M
112380 Ulcer Col-F	0.2	113502 Syn Fluid	0.0
		Cells4 RA
112734 Match	0.3	113495 Cartilage3 RA	0.0
Control Ulcer Col-F
112384 Ulcer Col-F	0.4	113496 Bone3 RA	0.0
112737 Match	0.1	113497 Synovium3 RA	0.0
Control Ulcer Col-F
112386 Ulcer Col-F	0.0	113498 Syn Fluid	0.0
		Cells3 RA
112738 Match	0.0	117106 Normal	0.3
Control Ulcer Col-F		Cartilage Rep20
112381 Ulcer Col-M	0.0	113663 Bone3 Normal	0.8
112735 Match	17.0	113664 Synovium3	0.3
Control Ulcer Col-M		Normal
112382 Ulcer Col-M	0.0	113665 Syn Fluid	0.7
		Cells3 Normal
112394 Match	0.0	117107 Normal	0.0
Control Ulcer Col-M		Cartilage Rep22
112383 Ulcer Col-M	0.0	113667 Bone4 Normal	0.1
112736 Match	0.0	113668 Synovium4	0.0
Control Ulcer Col-M		Normal
112423 Psoriasis-F	0.2	113669 Syn Fluid	0.1
		Cells4 Normal

[0642]

TABLE LC
Panel 1.3D
	Rel. Exp.(%)	Rel. Exp.(%)		Rel. Exp.(%)	Rel. Exp.(%)
	Ag3009, Run	Ag3009, Run		Ag3009, Run	Ag3009, Run
Tissue Name	161701362	163728052	Tissue Name	161701362	163728052
Liver	0.0	0.0	Kidney (fetal)	2.7	4.1
adenocarcinoma
Pancreas	0.0	0.0	Renal ca. 786-0	0.0	0.0
Pancreatic ca.	0.0	0.0	Renal ca.	0.0	0.0
CAPAN 2			A498
Adrenal gland	4.9	4.5	Renal ca. RXF	0.0	0.0
			393
Thyroid	0.0	0.0	Renal ca.	0.0	0.0
			ACHN
Salivary gland	0.0	0.1	Renal ca. UO-	0.0	0.0
			31
Pituitary gland	4.5	9.0	Renal ca. TK-	0.0	0.0
			10
Brain (fetal)	0.0	22.7	Liver	0.0	0.0
Brain (whole)	0.0	0.0	Liver (fetal)	7.7	9.4
Brain (amygdala)	0.0	0.0	Liver ca.	4.3	5.5
			(hepatoblast)
			HepG2
Brain	0.0	0.0	Lung	0.0	0.0
(cerebellum)
Brain	0.0	0.0	Lung (fetal)	0.1	0.1
(hippocampus)
Brain (substantia	0.1	0.1	Lung ca.	0.0	0.0
nigra)			(small cell)
			LX-1
Brain (thalamus)	0.0	0.0	Lung ca.	0.0	0.0
			(small cell)
			NCI-H69
Cerebral Cortex	0.0	0.0	Lung ca.	0.2	0.3
			(s.cell var.)
			SHP-77
Spinal cord	0.0	0.0	Lung ca.	0.0	0.0
			(large
			cell)NCI-
			H460
glio/astro	0.0	0.0	Lung ca. (non-	0.0	0.0
U87-MG			sm. cell) A549
glio/astro U-118-	0.0	0.0	Lung ca. (non-	0.1	0.1
MG			s.cell) NCI-
			H23
astrocytoma	0.0	0.0	Lung ca. (non-	0.0	0.0
SW1783			s.cell) HOP-62
neuro*; met	0.0	0.0	Lung ca. (non-	0.0	0.0
SK-N-AS			s.cl) NCI-
			H522
astrocytoma SF-	0.0	0.0	Lung ca.	0.0	0.0
539			(squam.) SW
			900
astrocytoma	0.0	0.0	Lung ca.	0.1	0.1
SNB-75			(squam.) NCI-
			H596
glioma SNB-19	0.0	0.0	Mammary	0.4	0.4
			gland
glioma U251	0.0	0.0	Breast ca.*	0.0	0.0
			(pl.ef) MCF-7
glioma SF-295	0.0	0.0	Breast ca.*	0.0	0.0
			(pl.ef) MDA-
			MB-231
Heart (fetal)	1.8	2.5	Breast ca.*	0.0	0.0
			(pl.ef) T47D
Heart	0.3	0.4	Breast ca. BT-	0.0	0.0
			549
Skeletal muscle	100.0	100.0	Breast ca.	0.0	0.0
(fetal)			MDA-N
Skeletal muscle	0.4	0.5	Ovary	1.7	2.3
Bone marrow	0.0	0.0	Ovarian ca.	0.0	0.0
			OVCAR-3
Thymus	0.1	0.1	Ovarian ca.	0.0	0.0
			OVCAR-4
Spleen	0.0	0.0	Ovarian ca.	0.0	0.0
			OVCAR-5
Lymph node	0.0	0.0	Ovarian ca.	0.0	0.0
			OVCAR-8
Colorectal	0.0	0.0	Ovarian ca.	0.0	0.0
			IGROV-1
Stomach	0.0	0.0	Ovarian ca.*	0.0	0.0
			(ascites) SK-
			OV-3
Small intestine	0.0	0.0	Uterus	0.0	0.0
Colon ca. SW480	0.0	0.0	Placenta	7.1	9.3
Colon ca.*	0.0	0.0	Prostate	0.0	0.0
SW620(SW480
met)
Colon ca. HT29	0.1	0.0	Prostate ca.*	0.0	0.0
			(bone met)
			PC-3
Colon ca. HCT-	0.0	0.0	Testis	0.4	0.6
116
Colon ca. CaCo-2	0.0	0.0	Melanoma	0.0	0.0
			Hs688(A).T
Colon ca.	0.0	0.0	Melanoma*	0.0	0.0
tissue (ODO3866)			(met)
			Hs688(B).T
Colon ca. HCC-	0.0	0.0	Melanoma	0.0	0.0
2998			UACC-62
Gastric ca.* (liver	0.0	0.0	Melanoma	0.0	0.0
met) NCI-N87			M14
Bladder	0.1	0.2	Melanoma	0.0	0.0
			LOX IMVI
Trachea	0.0	0.0	Melanoma*	0.1	0.1
			(met) SK-
			MEL-5
Kidney	0.0	0.0	Adipose	0.0	0.0

[0643]

TABLE LD
Panel 2D
	Rel. Exp.(%)	Rel. Exp.(%)		Rel. Exp.(%)	Rel. Exp.(%)
	Ag3009, Run	Ag3009, Run		Ag3009, Run	Ag3009, Run
Tissue Name	161701534	163578214	Tissue Name	161701534	163578214
Normal Colon	0.9	0.5	Kidney	1.1	1.1
			Margin
			8120608
CC Well to Mod	0.0	0.0	Kidney	0.0	0.0
Diff (ODO3866)			Cancer
			8120613
CC Margin	0.0	0.1	Kidney	0.1	0.0
(ODO3866)			Margin
			8120614
CC Gr.2	0.0	0.0	Kidney	100.0	100.0
rectosigmoid			Cancer
(ODO3868)			9010320
CC Margin	0.0	0.0	Kidney	0.3	0.2
(ODO3868)			Margin
			9010321
CC Mod Diff	0.0	0.0	Normal Uterus	0.0	0.1
(ODO3920)
CC Margin	0.0	0.0	Uterus Cancer	1.8	1.3
(ODO3920)			064011
CC Gr.2 ascend	0.0	0.0	Normal	0.5	0.5
colon			Thyroid
(ODO3921)
CC Margin	0.0	0.1	Thyroid	0.0	0.0
(ODO3921)			Cancer
			064010
CC from Partial	0.2	0.2	Thyroid	0.0	0.0
Hepatectomy			Cancer
(ODO4309)			A302152
Mets
Liver Margin	0.2	0.1	Thyroid	0.0	0.0
(ODO4309)			Margin
			A302153
Colon mets to	0.0	0.0	Normal Breast	5.4	5.1
lung (OD04451-
01)
Lung Margin	0.0	0.0	Breast Cancer	0.0	0.0
(OD04451-02)			(OD04566)
Normal Prostate	0.2	0.8	Breast Cancer	0.1	0.1
6546-1			(OD04590-01)
Prostate Cancer	0.0	0.0	Breast Cancer	0.0	0.0
(OD04410)			Mets
			(OD04590-03)
Prostate Margin	0.0	0.0	Breast Cancer	0.1	0.0
(OD04410)			Metastasis
			(OD04655-05)
Prostate Cancer	0.1	0.0	Breast Cancer	0.2	0.2
(OD04720-01)			064006
Prostate Margin	0.2	0.1	Breast Cancer	12.9	6.5
(OD04720-02)			1024
Normal Lung	0.6	0.7	Breast Cancer	8.7	10.0
061010			9100266
Lung Met to	0.0	0.0	Breast Margin	4.4	4.6
Muscle			9100265
(ODO4286)
Muscle Margin	15.1	10.9	Breast Cancer	4.9	5.5
(ODO4286)			A209073
Lung Malignant	0.0	0.1	Breast Margin	13.4	9.0
Cancer			A209073
(OD03126)
Lung Margin	0.0	0.0	Normal Liver	0.0	0.0
(OD03126)
Lung Cancer	0.0	0.0	Liver Cancer	0.0	0.1
(OD04404)			064003
Lung Margin	0.1	0.0	Liver Cancer	0.0	0.0
(OD04404)			1025
Lung Cancer	0.0	0.0	Liver Cancer	70.7	74.7
(OD04565)			1026
Lung Margin	0.0	0.0	Liver Cancer	0.0	0.0
(OD04565)			6004-T
Lung Cancer	0.0	0.0	Liver Tissue	0.0	0.0
(OD04237-01)			6004-N
Lung Margin	0.2	0.3	Liver Cancer	77.4	70.2
(OD04237-02)			6005-T
Ocular Mel Met	0.1	0.2	Liver Tissue	0.2	0.0
to Liver			6005-N
(ODO4310)
Liver Margin	2.6	2.2	Normal	7.9	3.0
(ODO4310)			Bladder
Melanoma Mets	1.9	2.2	Bladder	0.1	0.1
to Lung			Cancer 1023
(OD04321)
Lung Margin	0.0	0.0	Bladder	0.0	0.0
(OD04321)			Cancer
			A302173
Normal Kidney	0.1	0.0	Bladder	0.0	0.1
			Cancer
			(OD04718-01)
Kidney Ca,	0.0	0.0	Bladder	0.5	0.5
Nuclear grade 2			Normal
(OD04338)			Adjacent
			(OD04718-03)
Kidney Margin	0.1	0.0	Normal Ovary	22.4	19.8
(OD04338)
Kidney Ca	0.0	0.0	Ovarian	2.0	1.3
Nuclear grade			Cancer
1/2 (OD04339)			064008
Kidney Margin	0.5	0.3	Ovarian	0.0	0.0
(OD04339)			Cancer
			(OD04768-07)
Kidney Ca,	0.0	0.0	Ovary Margin	0.0	0.0
Clear cell type			(OD04768-08)
(OD04340)
Kidney Margin	1.0	0.7	Normal	0.0	0.0
(OD04340)			Stomach
Kidney Ca,	0.0	0.0	Gastric Cancer	0.1	0.1
Nuclear grade 3			9060358
(OD04348)
Kidney Margin	0.0	0.0	Stomach	0.0	0.1
(OD04348)			Margin
			9060359
Kidney Cancer	0.0	0.0	Gastric Cancer	0.0	0.0
(OD04622-01)			9060395
Kidney Margin	0.1	0.4	Stomach	0.0	0.0
(OD04622-03)			Margin
			9060394
Kidney Cancer	0.0	0.0	Gastric Cancer	0.0	0.2
(OD04450-01)			9060397
Kidney Margin	0.7	0.3	Stomach	0.0	0.0
(OD04450-03)			Margin
			9060396
Kidney Cancer	0.0	0.0	Gastric Cancer	0.0	0.1
8120607			064005

[0644]

TABLE LE
Panel 3D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag3009, Run		Ag3009, Run
Tissue Name	163482997	Tissue Name	163482997
Daoy- Medulloblastoma	0.1	Ca Ski- Cervical epidermoid	0.0
		carcinoma (metastasis)
TE671-	0.0	ES-2- Ovarian clear cell	0.0
Medulloblastoma		carcinoma
D283 Med-	0.0	Ramos- Stimulated with	0.0
Medulloblastoma		PMA/ionomycin 6h
PFSK-1- Primitive	12.5	Ramos- Stimulated with	0.0
Neuroectodermal		PMA/ionomycin 14h
XF-498- CNS	0.0	MEG-01- Chronic	0.0
		myelogenous leukemia
		(megokaryoblast)
SNB-78- Glioma	0.0	Raji- Burkitt's lymphoma	0.0
SF-268- Glioblastoma	0.0	Daudi- Burkitt's lymphoma	0.0
T98G- Glioblastoma	0.0	U266- B-cell plasmacytoma	0.0
SK-N-SH-	2.3	CA46- Burkitt's lymphoma	0.0
Neuroblastoma
(metastasis)
SF-295- Glioblastoma	0.0	RL- non-Hodgkin's B-cell	0.0
		lymphoma
Cerebellum	0.0	JM1- pre-B-cell lymphoma	0.0
Cerebellum	0.0	Jurkat- T cell leukemia	0.0
NCI-H292-	0.0	TF-1- Erythroleukemia	0.1
Mucoepidermoid lung
carcinoma
DMS-114- Small cell	0.1	HUT 78- T-cell lymphoma	0.0
lung cancer
DMS-79- Small cell lung	2.4	U937- Histiocytic lymphoma	0.0
cancer
NCI-H146- Small cell	29.1	KU-812- Myelogenous	4.8
lung cancer		leukemia
NCI-H526- Small cell	0.0	769-P- Clear cell renal	0.0
lung cancer		carcinoma
NCI-N417- Small cell	0.0	Caki-2- Clear cell renal	0.0
lung cancer		carcinoma
NCI-H82- Small cell	3.0	SW 839- Clear cell renal	0.0
lung cancer		carcinoma
NCI-H157- Squamous	0.0	G401- Wilms' tumor	1.0
cell lung cancer
(metastasis)
NCI-H1155- Large cell	18.8	Hs766T- Pancreatic	0.0
lung cancer		carcinoma (LN metastasis)
NCI-H1299- Large cell	0.0	CAPAN-1- Pancreatic	0.0
lung cancer		adenocarcinoma (liver
		metastasis)
NCI-H727- Lung	0.3	SU86.86- Pancreatic	0.0
carcinoid		carcinoma (liver metastasis)
NCI-UMC-11- Lung	0.0	BxPC-3- Pancreatic	0.0
carcinoid		adenocarcinoma
LX-1- Small cell lung	0.0	HPAC- Pancreatic	0.0
cancer		adenocarcinoma
Colo-205- Colon cancer	0.0	MIA PaCa-2- Pancreatic	0.0
		carcinoma
KM12- Colon cancer	0.0	CFPAC-1- Pancreatic ductal	0.0
		adenocarcinoma
KM20L2- Colon cancer	0.0	PANC-1- Pancreatic	0.2
		epithelioid ductal carcinoma
NCI-H716- Colon cancer	0.0	T24- Bladder carcinma	0.0
		(transitional cell)
SW-48- Colon	0.0	5637- Bladder carcinoma	0.0
adenocarcinoma
SW1116- Colon	0.1	HT-1197- Bladder carcinoma	0.0
adenocarcinoma
LS 174T- Colon	0.0	UM-UC-3- Bladder carcinma	0.0
adenocarcinoma		(transitional cell)
SW-948- Colon	0.0	A204- Rhabdomyosarcoma	100.0
adenocarcinoma
SW-480- Colon	0.0	HT-1080- Fibrosarcoma	0.0
adenocarcinoma
NCI-SNU-5- Gastric	0.0	MG-63- Osteosarcoma	0.0
carcinoma
KATO III- Gastric	0.0	SK-LMS-1- Leiomyosarcoma	0.0
carcinoma		(vulva)
NCI-SNU-16- Gastric	0.0	SJRH30-	0.0
carcinoma		Rhabdomyosarcoma (met to
		bone marrow)
NCI-SNU-1- Gastric	0.1	A431- Epidermoid carcinoma	0.0
carcinoma
RF-1- Gastric	0.0	WM266-4- Melanoma	0.0
adenocarcinoma
RF-48- Gastric	0.0	DU 145- Prostate carcinoma	0.0
adenocarcinoma		(brain metastasis)
MKN-45- Gastric	0.0	MDA-MB-468- Breast	0.0
carcinoma		adenocarcinoma
NCI-N87- Gastric	0.0	SCC-4- Squamous cell	0.0
carcinoma		carcinoma of tongue
OVCAR-5- Ovarian	0.0	SCC-9- Squamous cell	0.0
carcinoma		carcinoma of tongue
RL95-2- Uterine	0.0	SCC-15- Squamous cell	0.0
carcinoma		carcinoma of tongue
HelaS3- Cervical	0.0	CAL 27- Squamous cell	0.0
adenocarcinoma		carcinoma of tongue

[0645]

TABLE LF
PC-Panel 4D
	Rel.	Rel.	Rel.		Rel.	Rel.	Rel.
	Exp.(%)	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)	Exp.(%)
	Ag3009,	Ag3009,	Ag3009,		Ag3009,	Ag3009,	Ag3009,
Tissue	Run	Run	Run	Tissue	Run	Run	Run
Name	161701540	164043473	168033531	Name	161701540	164043473	168033531
Secondary Th1 act	0.0	0.0	0.9	HUVEC IL-	0.0	0.0	0.0
				1beta
Secondary Th2 act	0.0	0.0	0.0	HUVEC IFN	0.0	0.0	0.0
				gamma
Secondary Tr1 act	0.0	0.6	0.0	HUVEC TNF	0.0	0.0	0.0
				alpha + IFN
				gamma
Secondary Th1	0.0	0.0	0.0	HUVEC TNF	0.0	0.0	0.0
rest				alpha + IL4
Secondary Th2	0.0	0.0	0.0	HUVEC IL-11	0.0	0.0	0.0
rest
Secondary Tr1	0.0	0.0	0.0	Lung	0.0	0.0	0.0
rest				Microvascular
				EC none
Primary Th1 act	0.0	0.0	0.0	Lung	0.0	0.4	0.0
				Microvascular
				EC TNF alpha +
				IL-1beta
Primary Th2 act	0.0	0.0	0.0	Microvascular	0.1	0.0	0.0
				Dermal EC none
Primary Tr1 act	0.0	0.0	0.0	Microsvasular	0.0	0.0	0.0
				Dermal EC
				TNF alpha +
				IL-1beta
Primary Th1 rest	0.0	0.0	0.0	Bronchial	0.0	0.0	0.0
				epithelium
				TNF alpha +
				IL1beta
Primary Th2 rest	0.0	0.0	0.0	Small airway	0.0	0.0	0.0
				epithelium none
Primary Tr1 rest	0.0	0.0	0.0	Small airway	0.0	0.0	0.0
				epithelium
				TNF alpha +
				IL-1beta
CD45RA CD4	0.0	0.0	0.0	Coronery artery	0.0	0.0	0.0
lymphocyte act				SMC rest
CD45RO CD4	0.0	0.4	0.0	Coronery artery	0.0	0.0	0.0
lymphocyte act				SMC TNF
				alpha + IL-1beta
CD8 lymphocyte	0.0	0.0	0.5	Astrocytes rest	1.1	16.0	17.9
act
Secondary CD8	0.0	0.0	0.0	Astrocytes	0.7	0.7	2.1
lymphocyte rest				TNF alpha +
				IL-1beta
Secondary CD8	0.0	0.0	0.0	KU-812	6.5	100.0	88.3
lymphocyte act				(Basophil) rest
CD4 lymphocyte	0.0	0.0	0.0	KU-812	6.8	91.4	100.0
none				(Basophil)
				PMA/ionomycin
2ry	0.0	0.0	0.0	CCD1106	0.0	0.0	0.0
Th1/Th2/Tr1_anti-				(Keratinocytes)
CD95 CH11				none
LAK cells rest	0.0	0.0	0.0	CCD1106	0.0	0.0	0.0
				(Keratinocytes)
				TNF alpha +
				IL-1beta
LAK cells IL-2	0.0	0.0	0.0	Liver cirrhosis	0.1	1.4	1.9
LAK cells IL-2 +	0.0	0.5	0.0	Lupus kidney	0.0	0.0	0.0
IL-12
LAK cells IL-2 +	0.0	0.0	0.0	NCI-H292 none	0.0	0.0	0.0
IFN gamma
LAK cells IL-2 +	0.0	0.0	0.0	NCI-H292 IL-4	0.0	0.0	0.0
IL-18
LAK cells	0.0	0.4	0.0	NCI-H292 IL-9	100.0	0.0	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	0.0	0.0	NCI-H292 IL-	0.0	0.0	0.0
				13
Two Way MLR 3	0.0	0.0	0.0	NCI-H292 IFN	0.0	0.0	0.0
day				gamma
Two Way MLR 5	0.0	0.0	0.0	HPAEC none	0.0	0.0	0.0
day
Two Way MLR 7	0.0	0.0	0.0	HPAEC TNF	0.0	0.0	0.0
day				alpha + IL-1
				beta
PBMC rest	0.0	0.0	0.0	Lung fibroblast	0.0	0.0	0.0
				none
PBMC PWM	0.0	0.0	0.0	Lung fibroblast	0.0	0.0	0.0
				TNF alpha + IL-
				1beta
PBMC PHA-L	0.0	0.0	0.0	Lung fibroblast	0.0	0.0	0.0
				IL-4
Ramos (B cell)	0.0	0.0	0.0	Lung fibroblast	0.0	0.0	0.9
none				IL-9
Ramos (B cell)	0.0	0.0	0.0	Lung fibroblast	0.0	0.0	0.0
ionomycin				IL-13
B lymphocytes	0.0	0.0	0.0	Lung fibroblast	0.0	0.0	0.0
PWM				IFN gamma
B lymphocytes	0.0	0.0	0.0	Dermal	0.0	0.0	0.0
CD40L and IL-4				fibroblast
				CCD1070 rest
EOL-1 dbcAMP	0.0	0.0	0.0	Dermal	0.0	0.0	0.5
				fibroblast
				CCD1070 TNF
				alpha
EOL-1 dbcAMP	0.0	0.0	0.0	Dermal	0.0	0.0	0.0
PMA/ionomycin				fibroblast
				CCD1070 IL-1
				beta
Dendritic cells	0.0	0.0	0.0	Dermal	0.0	0.0	0.0
none				fibroblast IFN
				gamma
Dendritic cells	0.0	0.0	0.0	Dermal	0.0	0.0	0.0
LPS				fibroblast IL-4
Dendritic cells	0.0	0.0	0.0	IBD Colitis 2	0.0	0.0	0.0
anti-CD40
Monocytes rest	0.0	0.0	0.0	IBD Crohn's	0.0	0.0	1.4
Monocytes LPS	0.0	0.0	0.0	Colon	0.2	2.2	4.6
Macrophages rest	0.0	0.0	0.0	Lung	0.1	3.2	2.4
Macrophages LPS	0.0	0.0	0.0	Thymus	0.2	5.1	6.7
HUVEC none	0.0	0.0	0.0	Kidney	0.8	12.3	10.4
HUVEC starved	0.0	0.0	0.0

[0646] AI_comprehensive panel_v1.0 Summary: Ag3009 Highest expression of the CG91667-01 gene is seen in bone from an osteoarthritis patient (CT=24.8).

[0647] Panel 1.3D Summary: Ag3009 Two experiments with the same probe and primer set produce results that are in excellent agreement, with highest expression of the CG91667-01 gene, a DLK1 homolog, in fetal skeletal muscle (CTs=21-22). This expression is in agreement with published data that shows preferential expression of this gene in skeletal muscle.

[0648] In addition, this gene is expressed at much higher levels in fetal skeletal muscle when compared to expression in the adult counterpart (CTs=29). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue. Furthermore, 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 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.

[0649] This gene is also expressed at much higher levels in fetal liver (CT=25), lung (CT=32) and heart and kidney (CTs=27) when compared to expression in the adult heart (CT=30), lung, liver, and kidney (CTs=40). Thus, expression of this gene could be used to differentiate between the fetal and adult forms of lung, liver, kidney and heart. Dlkl has been implicated in the cells response to growth and differentiation signals (Ref.1, 2). The prominent expression of this gene in fetal tissues suggests that this Dlkl homolog may also be involved in cellular growth and proliferation.

[0650] There are also high levels of expression of this gene in a liver cancer cell line. In addition, low but significant expression of this gene is associated with lung and CNS cancer. Earlier DLK1 gene has been shown to be differentially expressed in small cell lung carcinoma and neuroendocrine tumor cell line (Ref.3). Therefore, therapeutic modulation of this gene, through the use of small molecule drugs, or antibodies could be of benefit in the treatment of liver, lung and CNS cancers.

[0651] See, generally,

[0652] Charlier C, Segers K, Wagenaar D, Karim L, Berghmans S, Jaillon O, Shay T, Weissenbach J, Cockett N, Gyapay G, Georges M. Human-ovine comparative sequencing of a 250-kb imprinted domain encompassing the callipyge (cipg) locus and identification of six imprinted transcripts: DLK1, DAT, GTL2, PEG11, antiPEG11, and MEG8. Genome Res 2001 May;11(5):850-62. PMID: 11337479

[0653] Baladron V, Jose Ruiz-Hidalgo M, Bonvini E, Gubina E, Notario V, Laborda J. The EGF-like Homeotic Protein dik Affects Cell Growth and Interacts with Growth-Modulating Molecules in the Yeast Two-Hybrid System. Biochem Biophys Res Commun 2002 Feb 22;291(2):193-204. PMID: 11846389

[0654] Laborda J, Sausville E A, Hoffman T, Notario V. (1993) dik, a putative mammalian homeotic gene differentially expressed in small cell lung carcinoma and neuroendocrine tumor cell line. J Biol Chem 268(6):3817-20. PMID: 8095043

[0655] Panel 2D Summary: Ag3009 Two experiments with the same probe and primer set produce results that are in excellent agreement, with highest expression of the CG91667-01 gene in kidney cancer (CTs=25). In addition, this gene is more highly expressed in liver and kidney tumors than in the corresponding matched normal tissue. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker for these cancers. This expression in kidney and liver cancers is in agreement with published reports that Dlk1 may be invovled in the cells response to growth and differentiation signals. Therefore, therapeutic targeting of this gene product with a human monoclonal antibody is anticipated to limit or block the extent of tumor cell growth and metastasis, particularly in kidney and liver tumors.

[0656] Panel 3D Summary: Ag3009 Highest expression of the CG91667-01 gene is seen in a rhabdomyosarcoma cell line (CT=25). Significant levels of expression are also seen in cell lines derived from lung cancer, myelogenous leukemia, neuroblastoma, and neuroectodermal tissue. Thus, expression of this gene could be used to differentiate between a rhabdomyosarcoma cell line and other samples on this panel.

[0657] This gene codes for delta like protein precursor (DLK), belonging to NOTCH family. Recently, a similar protein DLL4 belonging to NOTCH family has been shown to induces T-cell leukemia/lymphoma when overexpressed in mice by retroviral-mediated gene transfer (ref.1). Therefore, therapeutic modulation of this gene, through the use of small molecule drugs, or antibodies could be of benefit in the treatment of leukemia, lymphomas, blastomas and sarcomas.

[0658] See, generally,

[0659] Yan XQ, Sarmiento U, Sun Y, Huang G, Guo J, Juan T, Van G, Qi MY, Scully S, Senaldi G, Fletcher FA. (2001) A novel Notch ligand, D114, induces T-cell leukemia/lymphoma when overexpressed in mice by retroviral-mediated gene transfer. Blood 98(13):3793-9. PMID: 11739188

[0660] Panel 4D Summary: Ag3009 Two experiments with the same probe and primer set produce results that are in excellent agreement, with highest expression of the CG91667-01 gene in treated or untreated samples derived from the KU-812 basophil cell line (CTs=29-30). Low but significant levels of expression are also seen in resting astrocytes, colon, thymus, and kidney. Data from a third experiment with this probe and primer are not included because the amp plot indicates there were experimental difficulties with this run (Run 161701540).

[0661] Basophils release histamines and other biological modifiers in reponse to allergens and play an important role in the pathology of asthma and hypersensitivity reactions. Therefore, therapeutics designed against the putative protein encoded by this gene may reduce or inhibit inflammation by blocking basophil function in these diseases. In addition, these cells are a reasonable model for the inflammatory cells that take part in various inflammatory lung and bowel diseases, such as asthma, Crohn's disease, and ulcerative colitis. Therefore, therapeutics that modulate the function of this gene product may reduce or eliminate the symptoms of patients suffering from asthma, Crohn's disease, and ulcerative colitis.

[0662] M. NOV12a and NOV12b (CG92293-01 and CG92293-02: Polyprotein (ovochymase))

[0663] Expression of gene CG92293-01 and CG92293-02 was assessed using the primer-probe sets Ag3775 and Ag5273, described in Tables MA and MB. Results of the RTQ-PCR runs are shown in Tables MC, MD, ME and MF.

TABLE MA
Probe Name Ag3775
			Start SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-gcagattcaagtgcatgtgtta-3′	22	2032	147
Probe	TET-5′-ttactattctgcccatccaggaggga-3′-	26	2077	148
	TAMRA
Reverse	5′-gcacagatcatcttctctgtga-3′	22	2103	149

[0664]

TABLE MB
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-tgctctgaagcagagctagaaa-3′	22	2417	150
Probe	TET-5′-tttcccacaccacggtatctactgga-3′-	26	2453	151
	TAMRA
Reverse	5′-acccaagaacattccagtcttc-3′	22	2487	152

[0665]

TABLE MC
AI_comprehensive panel_v1.0
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag5273, Run		Ag5273, Run
Tissue Name	233667801	Tissue Name	233667801
110967 COPD-F	1.9	112427 Match Control	21.5
		Psoriasis-F
110980 COPD-F	15.7	112418 Psoriasis-M	4.8
110968 COPD-M	12.6	112723 Match Control	6.0
		Psoriasis-M
110977 COPD-M	48.0	112419 Psoriasis-M	21.8
110989 Emphysema-F	24.3	112424 Match Control	12.1
		Psoriasis-M
110992 Emphysema-F	3.8	112420 Psoriasis-M	28.5
110993 Emphysema-F	14.3	112425 Match Control	19.3
		Psoriasis-M
110994 Emphysema-F	11.3	104689 (MF) OA	18.0
		Bone-Backus
110995 Emphysema-F	5.9	104690 (MF) Adj	2.9
		“Normal” Bone-Backus
110996 Emphysema-F	6.2	104691 (MF) OA	17.7
		Synovium-Backus
110997 Asthma-M	6.9	104692 (BA) OA	7.7
		Cartilage-Backus
111001 Asthma-F	11.0	104694 (BA) OA	13.0
		Bone-Backus
111002 Asthma-F	15.9	104695 (BA) Adj	17.0
		“Normal” Bone-Backus
111003 Atopic	15.3	104696 (BA) OA	10.2
Asthma-F		Synovium-Backus
111004 Atopic	3.1	104700 (SS) OA Bone-Backus	11.8
Asthma-F
111005 Atopic	5.6	104701 (SS) Adj	36.6
Asthma-F		“Normal” Bone-Backus
111006 Atopic	1.6	104702 (SS) OA	23.3
Asthma-F		Synovium-Backus
111417 Allergy-M	4.5	117093 OA Cartilage	19.8
		Rep7
112347 Allergy-M	0.0	112672 OA Bone5	48.3
112349 Normal	0.0	112673 OA	23.3
Lung-F		Synovium5
112357 Normal	25.2	112674 OA Synovial	16.2
Lung-F		Fluid cells5
112354 Normal	15.3	117100 OA Cartilage	0.0
Lung-M		Rep14
112374 Crohns-F	5.7	112756 OA Bone9	0.0
112389 Match	13.1	112757 OA	6.0
Control Crohns-F		Synovium9
112375 Crohns-F	2.7	112758 OA Synovial	8.1
		Fluid Cells9
112732 Match	38.2	117125 RA Cartilage	9.5
Control Crohns-F		Rep2
112725 Crohns-M	5.8	113492 Bone2 RA	24.8
112387 Match	0.0	113493 Synovium2 RA	21.2
Control Crohns-M
112378 Crohns-M	1.3	113494 Syn Fluid Cells	61.1
		RA
112390 Match	12.7	113499 Cartilage4 RA	85.9
Control Crohns-M
112726 Crohns-M	9.7	113500 Bone4 RA	97.9
112731 Match	11.5	113501 Synovium4 RA	97.9
Control Crohns-M
112380 Ulcer Col-F	7.4	113502 Syn Fluid	62.9
		Cells4 RA
112734 Match	100.0	113495 Cartilage3 RA	47.0
Control Ulcer Col-F
112384 Ulcer Col-F	21.8	113496 Bone3 RA	70.7
112737 Match	5.4	113497 Synovium3 RA	20.7
Control Ulcer Col-F
112386 Ulcer Col-F	0.0	113498 Syn Fluid	63.3
		Cells3 RA
112738 Match	0.0	117106 Normal	0.0
Control Ulcer Col-F		Cartilage Rep20
112381 Ulcer Col-M	0.0	113663 Bone3 Normal	1.6
112735 Match	25.3	113664 Synovium3	0.0
Control Ulcer Col-M		Normal
112382 Ulcer Col-M	31.4	113665 Syn Fluid	0.0
		Cells3 Normal
112394 Match	6.4	117107 Normal	16.2
Control Ulcer Col-M		Cartilage Rep22
112383 Ulcer Col-M	8.7	113667 Bone4 Normal	13.9
112736 Match	2.9	113668 Synovium4	7.6
Control Ulcer Col-M		Normal
112423 Psoriasis-F	20.7	113669 Syn Fluid	20.7
		Cells4 Normal

[0666]

TABLE MD
CNS_neurodegeneration_v1.0
	Rel.	Rel.	Rel.		Rel.	Rel.	Rel.
	Exp.(%)	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)	Exp.(%)
	Ag3775,	Ag3775,	Ag5273,		Ag3775,	Ag3775,	Ag5273,
Tissue	Run	Run	Run	Tissue	Run	Run	Run
Name	211176610	224339887	230512547	Name	211176610	224339887	230512547
AD 1 Hippo	34.2	29.1	28.3	Control	4.4	2.1	6.3
				(Path) 3
				Temporal
				Ctx
AD 2 Hippo	33.4	25.7	30.4	Control	37.1	21.5	27.9
				(Path) 4
				Temporal
				Ctx
AD 3 Hippo	25.7	9.7	18.4	AD 1	24.7	19.9	26.4
				Occipital
				Ctx
AD 4 Hippo	9.0	8.1	13.9	AD 2	0.0	0.0	0.0
				Occipital
				Ctx
				(Missing)
AD 5 hippo	100.0	61.6	94.0	AD 3	8.1	9.0	9.4
				Occipital
				Ctx
AD 6 Hippo	88.9	100.0	100.0	AD 4	12.2	16.0	23.2
				Occipital
				Ctx
Control 2	10.7	20.9	24.7	AD 5	29.5	11.3	25.5
Hippo				Occipital
				Ctx
Control 4	12.2	5.9	10.8	AD 6	29.9	29.9	20.3
Hippo				Occipital
				Ctx
Control	4.7	2.8	5.3	Control 1	1.8	0.9	1.6
(Path) 3				Occipital
Hippo				Ctx
AD 1	24.0	26.8	18.7	Control 2	21.9	23.3	17.6
Temporal				Occipital
Ctx				Ctx
AD 2	22.2	21.5	47.3	Control 3	8.9	3.3	9.2
Temporal				Occipital
Ctx				Ctx
AD 3	15.9	5.0	26.8	Control 4	3.3	3.5	4.8
Temporal				Occipital
Ctx				Ctx
AD 4	16.2	21.9	18.9	Control	46.0	36.1	37.1
Temporal				(Path) 1
Ctx				Occipital
				Ctx
AD 5 Inf	79.0	36.1	90.8	Control	3.9	3.3	3.8
Temporal				(Path) 2
Ctx				Occipital
				Ctx
AD 5	73.2	47.3	64.6	Control	4.6	1.3	2.9
SupTemporal				(Path) 3
Ctx				Occipital
				Ctx
AD 6 Inf	70.2	33.9	76.8	Control	3.3	3.2	6.5
Temporal				(Path) 4
Ctx				Occipital
				Ctx
AD 6 Sup	74.2	51.1	88.3	Control 1	3.7	3.3	3.3
Temporal				Parietal
Ctx				Ctx
Control 1	1.4	3.7	5.2	Control 2	26.8	34.9	42.9
Temporal				Parietal
Ctx				Ctx
Control 2	18.7	12.9	29.1	Control 3	9.3	3.1	13.4
Temporal				Parietal
Ctx				Ctx
Control 3	8.4	6.5	6.6	Control	44.4	27.7	50.7
Temporal				(Path) 1
Ctx				Parietal
				Ctx
Control 4	14.2	2.9	8.4	Control	13.1	17.7	12.6
Temporal				(Path) 2
Ctx				Parietal
				Ctx
Control	53.6	29.5	42.9	Control	1.4	4.5	3.8
(Path) 1				(Path) 3
Temporal				Parietal
Ctx				Ctx
Control	43.2	21.8	44.8	Control	32.8	23.3	40.1
(Path) 2				(Path) 4
Temporal				Parietal
Ctx				Ctx

[0667]

TABLE ME
General_screening_panel_v1 .4
	Rel. Exp.(%) Ag3775,		Rel. Exp.(%) Ag3775,
Tissue Name	Run 219514534	Tissue Name	Run 219514534
Adipose	17.1	Renal ca.TK-10	0.0
Melanoma*	0.0	Bladder	3.9
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	21.6	Gastric ca. KATO III	0.0
Melanoma*	0.0	Colon ca. SW-948	0.0
LOXIMVI
Melanoma* SK-	5.2	Colon ca. SW480	0.0
MEL-5
Squamous cell	0.0	Colon ca.* (SW480	0.0
carcinoma SCC-4		met) SW620
Testis Pool	40.1	Colon ca. HT29	0.0
Prostate ca.* (bone	6.0	Colon ca. HCT-116	0.0
met) PC-3
Prostate Pool	5.7	Colon ca. CaCo-2	0.0
Placenta	0.0	Colon cancer tissue	12.8
Uterus Pool	6.1	Colon ca. SW1116	0.0
Ovarian ca.	100.0	Colon ca. Colo-205	0.0
OVCAR-3
Ovarian ca. SK-OV-3	5.4	Colon ca. SW-48	0.0
Ovarian ca.	0.0	Colon Pool	13.6
OVCAR-4
Ovarian ca.	0.0	Small Intestine Pool	12.2
OVCAR-5
Ovarian ca. IGROV-1	12.5	Stomach Pool	15.6
Ovarian ca.	11.3	Bone Marrow Pool	10.5
OVCAR-8
Ovary	12.1	Fetal Heart	3.7
Breast ca. MCF-7	10.4	Heart Pool	17.2
Breast ca. MDA-	0.0	Lymph Node Pool	24.5
MB-231
Breast ca. BT 549	56.3	Fetal Skeletal Muscle	14.7
Breast ca. T47D	0.0	Skeletal Muscle Pool	61.1
Breast ca. MDA-N	6.2	Spleen Pool	90.8
Breast Pool	9.9	Thymus Pool	40.3
Trachea	11.2	CNS cancer (glio/astro)	54.3
		U87-MG
Lung	9.7	CNS cancer (glio/astro)	0.0
		U-118-MG
Fetal Lung	3.8	CNS cancer	2.3
		(neuro;met) SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-	3.0
		539
Lung ca. LX-1	0.0	CNS cancer (astro)	35.1
		SNB-75
Lung ca. NCI-H146	0.0	CNS cancer (glio)	3.8
		SNB-19
Lung ca. SHP-77	12.3	CNS cancer (glio) SF-	39.5
		295
Lung ca. A549	0.0	Brain (Amygdala) Pool	21.5
Lung ca. NCI-H526	0.0	Brain (cerebellum)	6.4
Lung ca. NCI-H23	0.0	Brain (fetal)	45.1
Lung ca. NCI-H460	30.4	Brain (Hippocampus)	25.7
		Pool
Lung ca. HOP-62	23.0	Cerebral Cortex Pool	34.4
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	12.9
		Pool
Liver	3.8	Brain (Thalamus)Pool	36.3
Fetal Liver	3.1	Brain (whole)	33.7
Liver ca. HepG2	1.2	Spinal Cord Pool	21.5
Kidney Pool	27.7	Adrenal Gland	20.3
Fetal Kidney	49.0	Pituitary gland Pool	6.1
Renal ca. 786-0	0.0	Salivary Gland	6.6
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	1.9	Pancreatic ca.	0.0
		CAPAN2
Renal ca. UO-31	0.0	Pancreas Pool	18.9

[0668]

TABLE MF
Panel 4.1D
	Rel.	Rel.		Rel.	Rel.
	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)
	Ag3775,	Ag5273,		Ag3775,	Ag5273,
	Run	Run		Run	Run
Tissue Name	170129781	230500481	Tissue Name	170129781	230500481
Secondary Th1 act	0.0	0.0	HUVEC IL-1beta	5.1	5.8
Secondary Th2 act	51.4	40.3	HUVEC IFN	4.8	24.3
			gamma
Secondary Tr1 act	29.1	7.8	HUVEC TNF	1.4	0.0
			alpha + IFN
			gamma
Secondary Th1 rest	4.0	0.0	HUVEC TNF	4.7	1.1
			alpha + IL4
Secondary Th2 rest	20.0	10.2	HUVEC IL-11	1.8	4.4
Secondary Tr1 rest	14.9	0.0	Lung	0.0	2.3
			Microvascular EC
			none
Primary Th1 act	6.7	2.3	Lung	0.0	0.0
			Microvascular EC
			TNF alpha +
			IL-1beta
Primary Th2 act	10.4	7.6	Microvascular	0.0	0.0
			Dermal EC none
Primary Tr1 act	8.8	13.5	Microsvasular	0.0	0.0
			Dermal EC
			TNF alpha +
			IL-1beta
Primary Th1 rest	0.9	0.0	Bronchial	4.2	1.9
			epithelium
			TNF alpha +
			IL1beta
Primary Th2 rest	2.1	0.0	Small airway	0.0	2.4
			epithelium none
Primary Tr1 rest	13.4	3.2	Small airway	0.0	0.0
			epithelium
			TNF alpha +
			IL-1beta
CD45RA CD4	7.8	10.7	Coronery artery	2.8	4.9
lymphocyte act			SMC rest
CD45RO CD4	2.8	8.5	Coronery artery	2.0	5.1
lymphocyte act			SMC TNF
			alpha + IL-1beta
CD8 lymphocyte	6.6	1.7	Astrocytes rest	15.3	6.0
act
Secondary CD8	3.5	3.1	Astrocytes	9.1	5.4
lymphocyte rest			TNF alpha +
			IL-1beta
Secondary CD8	0.0	0.0	KU-812	4.3	0.0
lymphocyte act			(Basophil) rest
CD4 lymphocyte	3.9	6.7	KU-812	0.0	0.0
none			(Basophil)
			PMA/ionomycin
2ry	10.7	4.0	CCD1106	0.0	0.0
Th1/Th2/Tr1_anti-			(Keratinocytes)
CD95 CH11			none
LAK cells rest	7.8	2.5	CCD1106	2.2	0.0
			(Keratinocytes)
			TNF alpha +
			IL-1beta
LAK cells IL-2	5.8	0.0	Liver cirrhosis	1.5	0.0
LAK cells IL-2 +	11.2	0.0	NCI-H292 none	0.0	0.0
IL-12
LAK cells IL-2 +	11.2	0.0	NCI-H292 IL-4	0.0	0.0
IFN gamma
LAK cells IL-2 +	14.9	0.0	NCI-H292 IL-9	0.0	0.0
IL-18
LAK cells	13.5	14.8	NCI-H292 IL-13	0.0	0.0
PMA/ionomycin
NK Cells IL-2 rest	3.8	15.8	NCI-H292 IFN	0.0	2.0
			gamma
Two Way MLR 3	14.3	0.9	HPAEC none	0.0	0.9
day
Two Way MLR 5	2.5	2.2	HPAEC TNF	8.0	6.8
day			alpha + IL-1beta
Two Way MLR 7	2.0	0.0	Lung fibroblast	13.0	17.9
day			none
PBMC rest	0.0	0.0	Lung fibroblast	2.3	17.1
			TNF alpha + IL-1
			beta
PBMC PWM	3.8	0.0	Lung fibroblast	32.1	21.0
			IL-4
PBMC PHA-L	17.6	5.3	Lung fibroblast	56.6	25.2
			IL-9
Ramos (B cell)	0.0	0.0	Lung fibroblast	45.4	13.5
none			IL-13
Ramos (B cell)	0.0	0.0	Lung fibroblast	18.2	49.0
ionomycin			IFN gamma
B lymphocytes	1.9	0.0	Dermal fibroblast	9.0	0.0
PWM			CCD1070 rest
B lymphocytes	10.1	28.5	Dermal fibroblast	4.7	7.5
CD40L and IL-4			CCD1070 TNF
			alpha
EOL-1 dbcAMP	0.0	0.0	Dermal fibroblast	0.0	5.9
			CCD1070 IL-1
			beta
EOL-1 dbcAMP	0.0	0.0	Dermal fibroblast	38.4	20.3
PMA/ionomycin			IFN gamma
Dendritic cells	8.3	3.8	Dermal fibroblast	100.0	100.0
none			IL-4
Dendritic cells LPS	0.0	0.0	Dermal	5.3	9.8
			Fibroblasts rest
Dendritic cells anti-	15.4	8.0	Neutrophils	4.0	35.4
CD40			TNFa + LPS
Monocytes rest	1.1	2.7	Neutrophils rest	2.1	28.7
Monocytes LPS	9.4	11.2	Colon	0.0	0.0
Macrophages rest	7.2	0.0	Lung	21.8	4.0
Macrophages LPS	5.6	0.0	Thymus	57.4	14.7
HUVEC none	0.0	2.5	Kidney	2.2	0.0
HUVEC starved	0.0	2.7

[0669] AI_comprehensive panel_v1.0 Summary: Ag5273 The CG92293-01 gene appears to be slightly overexpressed in a cluster of samples derived from bone, cartilage, and synovium of rheumatoid arthritis patients (CTs=33-34). This expression profile suggests that therapeutic modulation of this gene product may reduce or eliminate the symptoms of patients suffering from rheumatoid arthritis.

[0670] CNS_neurodegeneration_v1.0 Summary: Ag3775 Two experiments with two probe and primer sets produce results that are in excellent agreement. This panel does not show differential expression of the CG92152-01 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain, with highest expression in the hippocampus of an Alzheimer's patient (CTs=31-32). Please see Panel 1.4 for discussion of utility of this gene in the central nervous system.

[0671] General_screening_panel_v1.4 Summary: Ag3775 Highest expression of the CG92152-01 gene is seen in an ovarian cancer cell line (CT=32). significant levels of expression are seen in a cluster of samples derived from breast and lung cancer cell lines. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and 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 ovarian, breast and lung cancers.

[0672] This gene is also expressed at 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.

[0673] Among tissues with metabolic function, this gene is expressed at low but significant levels in adipose, adrenal gland, pancreas, heart and adult and fetal skeletal muscle. This expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0674] Panel 4.1D Summary: Ag3775 Highest expression of the CG92152-01 gene in IL-4 treated with dermal fibroblasts (CTs=32.5). Low, but significant levels of expression are also seen in treated and untreated lung and dermal fibroblasts, and chronically activated Th2 cells. The expression of this gene in lung and skin derived fibroblasts suggests that this gene may be involved in normal conditions as well as pathological and inflammatory lung disorders that include chronic obstructive pulmonary disease, asthma, allergy, psoriasis, and emphysema.

[0675] N. NOV15a (CG92531-01: LEUCINE RICH)

[0676] Expression of gene CG92531-01 was assessed using the primer-probe set Ag3839, described in Table NA. Results of the RTQ-PCR runs are shown in Tables NB, NC and ND.

TABLE NA
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-ccggctacagtgctctttct-3′	20	5	153
Probe	TET-5′-ataaacccatgctggaaacaacccaa-3′-	26	26	154
	TAMRA
Reverse	5′-ggtaccacaccgtaccacaa-3′	20	83	155

[0677]

TABLE NB
CNS_neurodegeneration_v1.0
	Rel. Exp.(%) Ag3839,		Rel. Exp.(%) Ag3839,
Tissue Name	Run 212186726	Tissue Name	Run 212186726
AD 1 Hippo	11.0	Control (Path) 3	9.3
		Temporal Ctx
AD 2 Hippo	25.2	Control (Path) 4	44.4
		Temporal Ctx
AD 3 Hippo	17.3	AD 1 Occipital Ctx	37.9
AD 4 Hippo	11.7	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	90.1	AD 3 Occipital Ctx	13.2
AD 6 Hippo	51.1	AD 4 Occipital Ctx	27.4
Control 2 Hippo	17.0	AD 5 Occipital Ctx	46.0
Control 4 Hippo	14.6	AD 6 Occipital Ctx	20.4
Control (Path) 3	5.8	Control 1 Occipital	0.0
Hippo		Ctx
AD 1 Temporal Ctx	22.5	Control 2 Occipital	68.3
		Ctx
AD 2 Temporal Ctx	30.8	Control 3 Occipital	34.4
		Ctx
AD 3 Temporal Ctx	15.1	Control 4 Occipital	3.9
		Ctx
AD 4 Temporal Ctx	22.4	Control (Path) 1	100.0
		Occipital Ctx
AD 5 Inf Temporal	81.2	Control (Path) 2	14.9
Ctx		Occipital Ctx
AD 5 Sup	32.3	Control (Path) 3	4.1
Temporal Ctx		Occipital Ctx
AD 6 Inf Temporal	45.7	Control (Path) 4	24.8
Ctx		Occipital Ctx
AD 6 Sup	72.7	Control 1 Parietal	14.8
Temporal Ctx		Ctx
Control 1 Temporal	4.1	Control 2 Parietal	37.4
Ctx		Ctx
Control 2 Temporal	34.4	Control 3 Parietal	12.5
Ctx		Ctx
Control 3 Temporal	11.6	Control (Path) 1	84.1
Ctx		Parietal Ctx
Control 3 Temporal	7.6	Control (Path) 2	27.5
Ctx		Parietal Ctx
Control (Path) 1	65.5	Control (Path) 3	1.1
Temporal Ctx		Parietal Ctx
Control (Path) 2	31.2	Control (Path) 4	62.9
Temporal Ctx		Parietal Ctx

[0678]

TABLE NC
General_screening_panel_v1.4
	Rel. Exp.(%) Ag3839,		Rel. Exp.(%) Ag3839,
Tissue Name	Run 213604224	Tissue Name	Run 213604224
Adipose	12.9	Renal ca. TK-10	28.5
Melanoma*	10.4	Bladder	11.3
Hs688(A).T
Melanoma*	13.4	Gastric ca. (liver met.)	35.1
Hs688(B).T		NCI-N87
Melanoma* M14	16.7	Gastric ca. KATO III	50.0
Melanoma*	5.4	Colon ca. SW-948	14.8
LOXIMVI
Melanoma* SK-	10.1	Colon ca. SW480	21.3
MEL-5
Squamous cell	20.9	Colon ca.* (SW480	26.4
carcinoma SCC-4		met) SW620
Testis Pool	1.4	Colon ca. HT29	6.2
Prostate ca.* (bone	30.8	Colon ca. HCT-116	66.0
met) PC-3
Prostate Pool	16.3	Colon ca. CaCo-2	8.8
Placenta	5.5	Colon cancer tissue	6.2
Uterus Pool	14.1	Colon ca. SW1116	6.2
Ovarian ca.	19.5	Colon ca. Colo-205	3.5
OVCAR-3
Ovarian ca. SK-OV-3	33.4	Colon ca. SW-48	2.6
Ovarian ca.	29.3	Colon Pool	44.4
OVCAR-4
Ovarian ca.	49.0	Small Intestine Pool	38.2
OVCAR-5
Ovarian ca. IGROV-1	5.8	Stomach Pool	18.4
Ovarian ca.	3.8	Bone Marrow Pool	16.0
OVCAR-8
Ovary	27.0	Fetal Heart	3.4
Breast ca. MCF-7	7.6	Heart Pool	19.1
Breast ca. MDA-	44.1	Lymph Node Pool	50.7
MB-231
Breast ca. BT 549	23.0	Fetal Skeletal Muscle	5.1
Breast ca. T47D	83.5	Skeletal Muscle Pool	12.2
Breast ca. MDA-N	21.8	Spleen Pool	6.5
Breast Pool	42.6	Thymus Pool	22.2
Trachea	7.7	CNS cancer (glio/astro)	25.2
		U87-MG
Lung	15.3	CNS cancer (glio/astro)	100.0
		U-118-MG
Fetal Lung	8.4	CNS cancer	18.9
		(neuro;met) SK-N-AS
Lung ca. NCI-N417	2.3	CNS cancer (astro) SF-	6.8
		539
Lung ca. LX-1	20.4	CNS cancer (astro)	14.6
		SNB-75
Lung ca. NCI-H146	7.3	CNS cancer (glio)	5.0
		SNB-19
Lung ca. SHP-77	20.6	CNS cancer (glio) SF-	67.4
		295
Lung ca. A549	10.5	Brain (Amygdala) Pool	15.3
Lung ca. NCI-H526	1.7	Brain (cerebellum)	34.6
Lung ca. NCI-H23	57.8	Brain (fetal)	32.8
Lung ca. NCI-H460	10.2	Brain (Hippocampus)	6.8
		Pool
Lung ca. HOP-62	3.6	Cerebral Cortex Pool	19.3
Lung ca. NCI-H522	8.2	Brain (Substantia nigra)	13.3
		Pool
Liver	0.7	Brain (Thalamus) Pool	14.6
Fetal Liver	9.0	Brain (whole)	24.5
Liver ca. HepG2	6.1	Spinal Cord Pool	6.9
Kidney Pool	98.6	Adrenal Gland	24.0
Fetal Kidney	10.8	Pituitary gland Pool	5.8
Renal ca. 786-0	14.3	Salivary Gland	3.1
Renal ca. A498	0.8	Thyroid (female)	3.3
Renal ca. ACHN	12.9	Pancreatic ca.	12.2
		CAPAN2
Renal ca. UO-31	13.1	Pancreas Pool	29.1

[0679]

TABLE ND
Panel 4.1D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag3839, Run		Ag3839, Run
Tissue Name	170126776	Tissue Name	170126776
Secondary Th1 act	16.3	HUVEC IL-1beta	21.2
Secondary Th2 act	20.7	HUVEC IFN gamma	8.8
Secondary Tr1 act	25.5	HUVEC TNF alpha + IFN	48.6
		gamma
Secondary Th1 rest	6.0	HUVEC TNF alpha + IL4	73.2
Secondary Th2 rest	20.2	HUVEC IL-11	11.0
Secondary Tr1 rest	14.7	Lung Microvascular EC	97.9
		none
Primary Th1 act	20.9	Lung Microvascular EC	100.0
		TNF alpha + IL-1beta
Primary Th2 act	24.3	Microvascular Dermal EC	17.0
		none
Primary Tr1 act	15.2	Microsvasular Dermal EC	50.7
		TNF alpha + IL-1beta
Primary Th1 rest	13.4	Bronchial epithelium	22.4
		TNF alpha + IL1beta
Primary Th2 rest	12.4	Small airway epithelium	12.5
		none
Primary Tr1 rest	23.2	Small airway epithelium	39.0
		TNF alpha + IL-1beta
CD45RA CD4	23.2	Coronery artery SMC rest	18.8
lymphocyte act
CD45RO CD4	23.7	Coronery artery SMC	3.9
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	23.7	Astrocytes rest	6.4
Secondary CD8	22.2	Astrocytes TNF alpha +	4.8
lymphocyte rest		IL-1beta
Secondary CD8	13.0	KU-812 (Basophil) rest	10.3
lymphocyte act
CD4 lymphocyte none	8.4	KU-812 (Basophil)	9.2
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	12.4	CCD1106 (Keratinocytes)	18.7
CD95 CH11		none
LAK cells rest	16.0	CCD1106 (Keratinocytes)	12.4
		TNF alpha + IL-1beta
LAK cells IL-2	9.7	Liver cirrhosis	5.2
LAK cells IL-2+IL-12	8.0	NCI-H292 none	0.8
LAK cells IL-2+IFN	16.4	NCI-H292 IL-4	0.5
gamma
LAK cells IL-2+ IL-18	27.7	NCI-H292 IL-9	1.3
LAK cells	16.5	NCI-H292 IL-13	0.7
PMA/ionomycin
NK Cells IL-2 rest	25.9	NCI-H292 IFN gamma	1.4
Two Way MLR 3 day	17.2	HPAEC none	10.5
Two Way MLR 5 day	3.3	HPAEC TNF alpha +	15.6
		IL-1beta
Two Way MLR 7 day	5.1	Lung fibroblast none	15.7
PBMC rest	3.0	Lung fibroblast TNF	3.3
		alpha + IL-1beta
PBMC PWM	12.0	Lung fibroblast IL-4	15.6
PBMC PHA-L	10.7	Lung fibroblast IL-9	32.8
Ramos (B cell) none	11.3	Lung fibroblast IL-13	22.8
Ramos (B cell)	21.6	Lung fibroblast IFN	18.9
ionomycin		gamma
B lymphocytes PWM	14.0	Dermal fibroblast	36.9
		CCD1070 rest
B lymphocytes CD40L	16.6	Dermal fibroblast	31.9
and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	15.0	Dermal fibroblast	5.3
		CCD1070 IL-1beta
EOL-1 dbcAMP	10.2	Dermal fibroblast IFN	9.5
PMA/ionomycin		gamma
Dendritic cells none	2.6	Dermal fibroblast IL-4	9.9
Dendritic cells LPS	8.0	Dermal Fibroblasts rest	6.0
Dendritic cells anti-	5.6	Neutrophils TNFa + LPS	0.0
CD40
Monocytes rest	16.0	Neutrophils rest	1.6
Monocytes LPS	5.0	Colon	4.4
Macrophages rest	4.6	Lung	4.5
Macrophages LPS	2.6	Thymus	24.0
HUVEC none	3.4	Kidney	5.8
HUVEC starved	23.3

[0680] CNS_neurodegeneration_v1.0 Summary: Ag3839 This panel confirms the expression of CG92531-01 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. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.

[0681] General_screening_panel_v1.4 Summary: Ag3839 Highest expression of the CG92531-01 gene is detected in CNS cancer (glio/astro) cell line U-118-MG (CT=31.3). Significant expression of this gene is seen in cluster of cancer cell lines (CNS, colon, gastric, lung, breast, ovarian, prostate and melanoma) used in this panel. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, or antibodies, might be beneficial in the treatment of these cancers.

[0682] Among tissues with metabolic or endocrine function, this gene is expressed at low to moderate levels in pancreas, adipose, adrenal gland, thyroid, 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.

[0683] Interestingly, expression of this gene is higher in adult (CT=33) compared to the fetal heart sample (CT=36). Thus, expression of this gene can be used to distinguish between the adult and fetal heart.

[0684] In addition, this gene is expressed at low to 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.

[0685] Panel 4.1D Summary: Ag3839 Highest expression of the CG92531-01 gene is detected TNFalpha+IL-1 beta treated lung microvascular EC (CT=32). In addition, 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 crythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0686] O. NOV16a and NOV16b (CG92715-01 and CG92715-02: LRR protein)

[0687] Expression of gene CG92715-01 and CG92715-02 was assessed using the primer-probe set Ag2502, described in Table OA. Results of the RTQ-PCR runs are shown in Tables OB, OC, OD, OE and OF.

TABLE OA
Probe Name Ag2502
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-ggagtaaccacttcacctcctt-3′	22	1632	156
Probe	TET-5′-ccagctgaagtcactcatccaaatcg-3′-TAMRA	26	1675	157
Reverse	5′-aggtacaatcccaaggattgtc-3′	22	1709	158

[0688]

TABLE OB
CNS_neurodegeneration_v1.0
	Rel. Exp.(%) Ag2502,		Rel. Exp.(%) Ag2502,
Tissue Name	Run 208776914	Tissue Name	Run 208776914
AD 1 Hippo	9.9	Control (Path) 3	1.8
		Temporal Ctx
AD 2 Hippo	20.4	Control (Path) 4	29.9
		Temporal Ctx
AD 3 Hippo	4.9	AD 1 Occipital Ctx	11.8
AD 4 Hippo	4.2	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	100.0	AD 3 Occipital Ctx	4.5
AD 6 Hippo	35.8	AD 4 Occipital Ctx	14.8
Control 2 Hippo	21.5	AD 5 Occipital Ctx	13.3
Control 4 Hippo	4.6	AD 6 Occipital Ctx	36.9
Control (Path) 3	2.4	Control 1 Occipital	0.8
Hippo		Ctx
AD 1 Temporal Ctx	10.8	Control 2 Occipital	53.6
		Ctx
AD 2 Temporal Ctx	30.1	Control 3 Occipital	13.2
		Ctx
AD 3 Temporal Ctx	3.3	Control 4 Occipital	2.9
		Ctx
AD 4 Temporal Ctx	15.6	Control (Path) 1	84.7
		Occipital Ctx
AD 5 Inf Temporal	92.7	Control (Path) 2	7.5
Ctx		Occipital Ctx
AD 5 SupTemporal	40.9	Control (Path) 3	1.1
Ctx		Occipital Ctx
AD 6 Inf Temporal	51.8	Control (Path) 4	17.3
Ctx		Occipital Ctx
AD 6 Sup Temporal	50.7	Control 1 Parietal	2.9
Ctx		Ctx
Control 1 Temporal	2.8	Control 2 Parietal	37.1
Ctx		Ctx
Control 2 Temporal	31.6	Control 3 Parietal	17.0
Ctx		Ctx
Control 3 Temporal	16.3	Control (Path) 1	75.3
Ctx		Parietal Ctx
Control 4 Temporal	5.6	Control (Path) 2	19.6
Ctx		Parietal Ctx
Control (Path) 1	68.3	Control (Path) 3	2.2
Temporal Ctx		Parietal Ctx
Control (Path) 2	31.6	Control (Path) 4	44.1
Temporal Ctx		Parietal Ctx

[0689]

TABLE OC
Panel 1.3D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag2502, Run		Ag2502, Run
Tissue Name	162431037	Tissue Name	162431037
Liver adenocarcinoma	1.6	Kidney (fetal)	0.9
Pancreas	0.6	Renal ca. 786-0	3.3
Pancreatic ca. CAPAN 2	1.3	Renal ca. A498	0.7
Adrenal gland	0.0	Renal ca. RXF 393	0.0
Thyroid	2.8	Renal ca. ACHN	0.3
Salivary gland	3.0	Renal ca. UO-31	1.0
Pituitary gland	0.6	Renal ca. TK-10	1.0
Brain (fetal)	4.8	Liver	0.0
Brain (whole)	9.7	Liver (fetal)	0.0
Brain (amygdala)	8.1	Liver ca.	0.0
		(hepatoblast) HepG2
Brain (cerebellum)	7.1	Lung	0.2
Brain (hippocampus)	16.5	Lung (fetal)	0.8
Brain (substantia nigra)	0.6	Lung ca. (small cell)	0.3
		LX-1
Brain (thalamus)	2.9	Lung ca. (small cell)	2.4
		NCI-H69
Cerebral Cortex	100.0	Lung ca. (s.cell var.)	10.7
		SHP-77
Spinal cord	7.3	Lung ca. (large	1.4
		cell)NCI-H460
glio/astro U87-MG	12.5	Lung ca. (non-sm.	0.5
		cell) A549
glio/astro U-118-MG	2.7	Lung ca. (non-s.cell)	16.8
		NCI-H23
astrocytoma SW1783	0.3	Lung ca. (non-s.cell)	1.4
		HOP-62
neuro*; met SK-N-AS	3.4	Lung ca. (non-s.cl)	0.3
		NCI-H522
astrocytoma SF-539	0.0	Lung ca. (squam.)	0.7
		SW 900
astrocytoma SNB-75	0.7	Lung ca. (squam.)	4.0
		NCI-H596
glioma SNB-19	0.2	Mammary gland	0.2
glioma U251	1.4	Breast ca.* (pl.ef)	0.0
		MCF-7
glioma SF-295	0.2	Breast ca.* (pl.ef)	0.0
		MDA-MB-231
Heart (fetal)	0.2	Breast ca.* (pl.ef)	0.9
		T47D
Heart	0.2	Breast Ca. BT-549	1.4
Skeletal muscle (fetal)	17.3	Breast ca. MDA-N	0.4
Skeletal muscle	0.4	Ovary	5.0
Bone marrow	0.0	Ovarian ca.	3.1
		OVCAR-3
Thymus	0.1	Ovarian ca.	0.2
		OVCAR-4
Spleen	0.0	Ovarian ca.	0.0
		OVCAR-5
Lymph node	0.0	Ovarian ca.	8.3
		OVCAR-8
Colorectal	1.4	Ovarian ca. IGROV-1	0.2
Stomach	0.1	Ovarian ca.*	0.2
		(ascites) SK-OV-3
Small intestine	0.4	Uterus	0.1
Colon ca. SW480	0.0	Placenta	0.0
Colon ca.*	0.5	Prostate	0.7
SW620(SW480 met)
Colon ca. HT29	0.0	Prostate ca.* (bonemet)	0.6
		PC-3
Colon ca. HCT-116	0.0	Testis	0.5
Colon ca. CaCo-2	0.0	Melanoma	0.0
		Hs688(A).T
Colon ca.	0.0	Melanoma* (met)	0.0
tissue(ODO3866)		Hs688(B).T
Colon ca. HCC-2998	1.3	Melanoma UACC-	0.1
		62
Gastric ca.* (liver met)	0.0	Melanoma M14	0.2
NCI-N87
Bladder	0.7	Melanoma LOX	0.8
		IMVI
Trachea	1.9	Melanoma* (met)SK-MEL-5	1.3
Kidney	0.1	Adipose	1.3

[0690]

TABLE OD
Panel 2D
	Rel. Exp.(%)	Rel. Exp.(%)		Rel. Exp.(%)	Rel. Exp.(%)
	Ag2502,	Ag2502,		Ag2502,	Ag2502,
	Run	Run		Run	Run
Tissue Name	162319639	164993363	Tissue Name	162319639	164993363
Normal Colon	7.1	9.9	Kidney	0.1	0.1
			Margin
			8120608
CC Well to Mod	0.0	0.1	Kidney	0.0	0.1
Diff (ODO3866)			Cancer
			8120613
CC Margin	0.7	0.3	Kidney	0.2	0.6
(ODO3866)			Margin
			8120614
CC Gr.2	0.3	0.0	Kidney	1.4	2.1
rectosigmoid			Cancer
(ODO3868)			9010320
CC Margin	0.4	0.8	Kidney	0.6	0.2
(ODO3868)			Margin
			9010321
CC Mod Diff	10.5	11.1	Normal Uterus	0.1	0.1
(ODO3920)
CC Margin	1.0	1.5	Uterus Cancer	0.3	0.7
(ODO3920)			064011
CC Gr.2 ascend	2.8	1.3	Normal	14.5	13.5
colon			Thyroid
(ODO3921)
CC Margin	0.1	0.2	Thyroid	0.4	0.3
(ODO3921)			Cancer
			064010
CC from Partial	0.0	0.0	Thyroid	0.2	0.6
Hepatectomy			Cancer
(ODO4309)			A302152
Mets
Liver Margin	0.1	0.1	Thyroid	14.9	12.4
(ODO4309)			Margin
			A302153
Colon mets to	0.9	1.3	Normal Breast	1.7	2.6
lung (OD04451-
01)
Lung Margin	0.9	0.4	Breast Cancer	0.1	0.2
(OD04451-02)			(OD04566)
Normal Prostate	13.8	7.2	Breast Cancer	5.5	5.1
6546-1			(OD04590-01)
Prostate Cancer	19.1	15.9	Breast Cancer	4.2	2.6
(OD04410)			Mets
			(OD04590-03)
Prostate Margin	7.0	8.5	Breast Cancer	1.0	0.9
(OD04410)			Metastasis
			(OD04655-05)
Prostate Cancer	33.2	34.9	Breast Cancer	1.3	0.4
(OD04720-01)			064006
Prostate Margin	43.5	56.6	Breast Cancer	2.1	1.1
(OD04720-02)			1024
Normal Lung	2.8	3.0	Breast Cancer	0.1	0.1
061010			9100266
Lung Met to	15.8	14.3	Breast Margin	2.5	2.5
Muscle			9100265
(ODO4286)
Muscle Margin	0.5	0.6	Breast Cancer	2.4	0.6
(ODO4286)			A209073
Lung Malignant	0.9	0.7	Breast Margin	3.7	3.3
Cancer			A209073
(OD03126)
Lung Margin	1.2	1.9	Normal Liver	0.0	0.1
(OD03126)
Lung Cancer	0.3	0.3	Liver Cancer	0.6	1.2
(OD04404)			064003
Lung Margin	0.4	0.5	Liver Cancer	0.0	0.0
(OD04404)			1025
Lung Cancer	0.1	0.5	Liver Cancer	0.0	0.1
(OD04565)			1026
Lung Margin	0.3	1.0	Liver Cancer	0.0	0.0
(OD04565)			6004-T
Lung Cancer	1.7	1.7	Liver Tissue	0.3	0.2
(OD04237-01)			6004-N
Lung Margin	0.1	0.0	Liver Cancer	0.1	0.0
(OD04237-02)			6005-T
Ocular Mel Met	0.0	0.0	Liver Tissue	0.0	0.0
to Liver			6005-N
(ODO4310)
Liver Margin	0.2	0.0	Normal	6.5	4.0
(ODO4310)			Bladder
Melanoma Mets	0.0	0.1	Bladder	0.0	0.3
to Lung			Cancer 1023
(OD04321)
Lung Margin	0.4	0.6	Bladder	24.0	23.5
(OD04321)			Cancer
			A302173
Normal Kidney	2.3	1.9	Bladder	0.0	0.0
			Cancer
			(OD04718-01)
Kidney Ca,	2.8	2.9	Bladder	0.1	0.1
Nuclear grade 2			Normal
(OD04338)			Adjacent
			(OD04718-03)
Kidney Margin	0.4	0.3	Normal Ovary	2.1	3.9
(OD04338)
Kidney Ca	0.4	0.3	Ovarian	4.9	6.3
Nuclear grade			Cancer
1/2 (OD04339)			064008
Kidney Margin	0.4	0.9	Ovarian	10.4	7.8
(OD04339)			Cancer
			(OD04768-07)
Kidney Ca,	27.4	33.2	Ovary Margin	0.4	0.2
Clear cell type			(OD04768-08)
(OD04340)
Kidney Margin	0.2	0.3	Normal	6.2	5.2
(OD04340)			Stomach
Kidney Ca,	3.0	3.0	Gastric Cancer	3.1	7.5
Nuclear grade 3			9060358
(OD04348)
Kidney Margin	0.4	0.0	Stomach	1.3	0.8
(OD04348)			Margin
			9060359
Kidney Cancer	100.0	100.0	Gastric Cancer	4.7	4.3
(OD04622-01)			9060395
Kidney Margin	0.0	0.5	Stomach	1.5	1.3
(OD04622-03)			Margin
			9060394
Kidney Cancer	0.1	0.8	Gastric Cancer	1.4	1.2
(OD04450-01)			9060397
Kidney Margin	0.8	0.7	Stomach	0.2	0.2
(OD04450-03)			Margin
			9060396
Kidney Cancer	4.7	3.7	Gastric Cancer	4.7	3.0
8120607			064005

[0691]

TABLE OE
Panel 3D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag2502, Run		Ag2502, Run
Tissue Name	164629448	Tissue Name	164629448
Daoy- Medulloblastoma	1.6	Ca Ski- Cervical epidermoid	1.2
		carcinoma (metastasis)
TE671-	41.8	ES-2- Ovarian clear cell	22.5
Medulloblastoma		carcinoma
D283 Med-	63.7	Ramos- Stimulated with	0.0
Medulloblastoma		PMA/ionomycin 6h
PFSK-1- Primitive	0.0	Ramos- Stimulated with	0.0
Neuroectodermal		PMA/ionomycin 14h
XF-498- CNS	22.8	MEG-01- Chronic	13.8
		myelogenous leukemia
		(megokaryoblast)
SNB-78- Glioma	11.8	Raji- Burkitt's lymphoma	0.0
SF-268- Glioblastoma	5.1	Daudi- Burkitt's lymphoma	0.0
T98G- Glioblastoma	0.0	U266- B-cell plasmacytoma	8.5
SK-N-SH-	0.0	CA46- Burkitt's lymphoma	6.3
Neuroblastoma
(metastasis)
SF-295- Glioblastoma	0.8	RL- non-Hodgkin's B-cell	0.0
		lymphoma
Cerebellum	79.0	JM1- pre-B-cell lymphoma	0.0
Cerebellum	26.4	Jurkat- T cell leukemia	0.0
NCI-H292-	1.5	TF-1- Erythroleukemia	11.8
Mucoepidermoid lung
carcinoma
DMS-114- Small cell	13.2	HUT 78- T-cell lymphoma	0.0
lung cancer
DMS-79- Small cell lung	0.0	U937- Histiocytic lymphoma	0.0
cancer
NCI-H146- Small cell	28.5	KU-812- Myelogenous	0.3
lung cancer		leukemia
NCI-H526- Small cell	3.1	769-P- Clear cell renal	9.5
lung cancer		carcinoma
NCI-N417- Small cell	46.3	Caki-2- Clear cell renal	3.1
lung cancer		carcinoma
NCI-H82- Small cell	87.1	SW 839- Clear cell renal	12.5
lung cancer		carcinoma
NCI-H157- Squamous	100.0	G401- Wilms' tumor	12.6
cell lung cancer
(metastasis)
NCI-H1155- Large cell	35.6	Hs766T- Pancreatic	0.0
lung cancer		carcinoma (LN metastasis)
NCI-H1299- Large cell	16.5	CAPAN-1- Pancreatic	0.0
lung cancer		adenocarcinoma (liver
		metastasis)
NCI-H727- Lung	0.0	SU86.86- Pancreatic	2.4
carcinoid		carcinoma (liver metastasis)
NCI-UMC-11- Lung	53.2	BxPC-3- Pancreatic	0.0
carcinoid		adenocarcinoma
LX-1- Small cell lung	1.2	HPAC- Pancreatic	0.0
cancer		adenocarcinoma
Colo-205- Colon cancer	5.9	MIA PaCa-2- Pancreatic	0.7
		carcinoma
KM12- Colon cancer	0.0	CFPAC-1- Pancreatic ductal	0.4
		adenocarcinoma
KM20L2- Colon cancer	0.0	PANC-1- Pancreatic	1.3
		epithelioid ductal carcinoma
NCI-H716- Colon cancer	0.0	T24- Bladder carcinma	0.0
		(transitional cell)
SW-48- Colon	0.0	5637- Bladder Carcinoma	7.7
adenocarcinoma
SW1116- Colon	0.0	HT-1197- Bladder Carcinoma	0.0
adenocarcinoma
LS 174T- Colon	0.0	UM-UC-3- Bladder carcinma	3.1
adenocarcinoma		(transitional cell)
SW-948- Colon	0.0	A204- Rhabdomyosarcoma	0.0
adenocarcinoma
SW-480- Colon	0.0	HT-1080- Fibrosarcoma	2.6
adenocarcinoma
NCI-SNU-5- Gastric	0.0	MG-63- Osteosarcoma	4.6
carcinoma
KATO III- Gastric	0.0	SK-LMS-1- Leiomyosarcoma	0.3
carcinoma		(vulva)
NCI-SNU-16- Gastric	6.7	SJRH30-	22.8
carcinoma		Rhabdomyosarcoma (met to
		bone marrow)
NCI-SNU-1- Gastric	0.0	A431- Epidermoid carcinoma	0.0
carcinoma
RF-1- Gastric	2.4	WM266-4- Melanoma	15.8
adenocarcinoma
RF-48- Gastric	2.6	DU 145- Prostate carcinoma	0.0
adenocarcinoma		(brain metastasis)
MKN-45- Gastric	0.0	MDA-MB-468- Breast	0.3
carcinoma		adenocarcinoma
NCI-N87- Gastric	0.0	SCC-4- Squamous cell	0.0
carcinoma		carcinoma of tongue
OVCAR-5- Ovarian	0.0	SCC-9- Squamous cell	0.0
carcinoma		carcinoma of tongue
RL95-2- Uterine	1.7	SCC-15- Squamous cell	0.0
carcinoma		carcinoma of tongue
HelaS3- Cervical	14.6	CAL 27- Squamous cell	0.0
adenocarcinoma		carcinoma of tongue

[0692]

TABLE OF
Panel 4D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag2502, Run		Ag2502, Run
Tissue Name	162293442	Tissue Name	162293442
Secondary Th1 act	1.6	HUVEC IL-1beta	3.5
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	0.0
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	3.7
Secondary Tr1 rest	0.0	Lung Microvascular EC	2.8
		none
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	9.7
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	23.0
		none
Primary Tr1 rest	1.8	Small airway epithelium	0.0
		TNF alpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	0.0
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	21.6
Secondary CD8	0.0	Astrocytes TNF alpha +	4.1
lymphocyte rest		IL-1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	0.0
lymphocyte act
CD4 lymphocyte none	3.1	KU-812 (Basophil)	46.3
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	1.1	CCD1106 (Keratinocytes)	2.5
CD95 CH11		none
LAK cells rest	4.1	CCD1106 (Keratinocytes)	6.9
		TNF alpha + IL-1beta
LAK cells IL-2	6.6	Liver cirrhosis	16.6
LAK cells IL-2 + IL-12	0.0	Lupus kidney	2.6
LAK cells IL-2 + IFN	2.4	NCI-H292 none	57.8
gamma
LAK cells IL-2 + IL-18	4.4	NCI-H292 IL-4	26.8
LAK cells	0.0	NCI-H292 IL-9	54.3
PMA/ionomycin
NK Cells IL-2 rest	2.4	NCI-H292 IL-13	24.0
Two Way MLR 3 day	0.0	NCI-H292 IFN gamma	20.7
Two Way MLR 5 day	0.0	HPAEC none	0.0
Two Way MLR 7 day	0.0	HPAEC TNF alpha + IL-1	0.0
		beta
PBMC rest	7.8	Lung fibroblast none	5.8
PBMC PWM	6.7	Lung fibroblast TNF	0.0
		alpha + IL-1beta
PBMC PHA-L	0.0	Lung fibroblast IL-4	31.4
Ramos (B cell) none	6.6	Lung fibroblast IL-9	7.6
Ramos (B cell)	8.8	Lung fibroblast IL-13	3.0
ionomycin
B lymphocytes PWM	0.0	Lung fibroblast IFN	5.3
		gamma
B lymphocytes CD40L	0.0	Dermal fibroblast	9.5
and IL-4		CCD1070 rest
EOL-1 dbcAMP	100.0	Dermal fibroblast	0.0
		CCD1070 TNF alpha
EOL-1 dbcAMP	18.2	Dermal fibroblast	0.0
PMA/ionomycin		CCD1070 IL-1beta
Dendritic cells none	0.0	Dermal fibroblast IFN	0.0
		gamma
Dendritic cells LPS	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells anti-	0.0	IBD Colitis 2	6.0
CD40
Monocytes rest	3.5	IBD Crohn's	1.3
Monocytes LPS	0.0	Colon	31.4
Macrophages rest	0.0	Lung	56.3
Macrophages LPS	0.0	Thymus	25.3
HUVEC none	0.0	Kidney	12.2
HUVEC starved	23.3

[0693] CNS_neurodegeneration_v1.0 Summary: Ag2502 This panel does not show differential expression of the CG92715-01 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain, with highest expression in the hippocampus from an Alzheimer's patient (CT=26.9). Please see Panel 1.3D for discussion of utility of this gene in the central nervous system.

[0694] Panel 1.3D Summary: Ag2502 Highest expression of the CG92715-01 gene is seen in the cerebral cortex (CT=27). In addition, low levels of expression are seen in all CNS regions examined in this panel. This gene encodes a leucine-rich repeat protein. Leucine rich repeats (LRR) mediate reversible protein-protein interactions and have diverse cellular functions, including cellular adhesion and signaling. Several of these proteins, such as connectin, slit, chaoptin, and Toll have pivotal roles in neuronal development in Drosophila and may play significant but distinct roles in neural development and in the adult nervous system of humans (Ref. 1). In Drosophilia, the LRR region of axon guidance proteins has been shown to be critical for their function (especially in axon repulsion). Since the leucine-rich-repeat protein encoded by this gene shows high expression in the cerebral cortex, it is an excellent candidate neuronal guidance protein for axons, dendrites and/or growth cones in general. Therefore, therapeutic modulation of the levels of this protein, or possible signaling via this protein, may be of utility in enhancing/directing compensatory synaptogenesis and fiber growth in the CNS in response to neuronal death (stroke, head trauma), axon lesion (spinal cord injury), or neurodegeneration (Alzheimer's, Parkinson's, Huntington's, vascular dementia or any neurodegenerative disease).

[0695] Moderate levels of expression are also seen in cell lines derived from ovarian cancer, lung cancer, and brain cancer. Therefore, therapeutic modulation of the expression or function of this gene product may be effective in the treatment of these cancers.

[0696] Among metabolically relevant tissues, this gene expression is seen in fetal skeletal muscle, thyroid, and pituitary gland. This observation suggests that therapeutic modulation may aid the treatment of metabolic diseases such as obesity and diabetes as well as neuroendocrine disorders. Glycoprotein hormones influence the development and function of the ovary, testis and thyroid by binding to specific high-affinity receptors. Interestingly, the extracellular domains of these receptors are members of the leucine-rich repeat (LRR) protein superfamily and are responsible for the high-affinity binding.

[0697] Results from a second experiment with the same probe and primer set are not included (Run 165518160). The amp plot indicates that there were experimental difficulties with this run.

[0698] See, generally,

[0699] Jiang X., Dreano M., Buckler D. R., Cheng S., Ythier A., Wu H., Hendrickson W. A., el Tayar N. (1995) Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone-receptor interactions. Structure 3: 1341-1353. PMID: 8747461

[0700] Battye R., Stevens A., Perry R. L., Jacobs J. R. (2001) Repellent signaling by Slit requires the leucine-rich repeats. J. Neurosci. 21: 4290-4298. PMID: 11404414

[0701] Itoh A., Miyabayashi T., Ohno M., Sakano S. 1998 Cloning and expressions of three mammalian homologues of Drosophila slit suggest possible roles for Slit in the formation and maintenance of the nervous system. Brain Res. Mol. Brain Res. 62: 175-186. PMID: 9813312

[0702] Panel 2D Summary: Ag2502 Two experiments with the same probe and primer set produce results that are in excellent agreement. Highest expression of the CG92715-01 gene is seen in kidney cancer (CTs=27.7). In addition, expression is significantly higher in the kidney cancer when compared to expression in the normal adjacent tissue, suggesting a role in renal cancer progression. There is also moderate to low expression in bladder, gastric, colon and ovarian cancers. Thus, expression of this gene could be used to differentiate the kidney cancer samples from other samples on this panel and as a marker for kidney cancer. Furthermore, therapeutic targeting of the CG92715-01 gene with a human monoclonal antibody is anticipated to limit or block the extent of tumor cell migration, invasion, and metastasis, specifically in kidney, ovarian, bladder, gastric, and colon tumors.

[0703] Panel 3D Summary: Ag2502 Highest expression of the CG92715-01 gene is seen in a lung cancer cell line (CT=28). In addition, moderate levels of expression are seen in a cluster of lung and brain cancer cell lines. Prominent expression is also seen in cerebellum, in agreement with expression seen in Panel 1.3D. Low, but significant expression is also seen in kidney cancer and ovarian cancer cell lines. Thus, expression of this gene could be used to differentiate lung and brain cancer cell lines and normal brain from other samples on this panel and as a marker for lung and brain cancer. In addition, moderate expression of this gene is also seen in melanoma, rhabdomyosarcoma, osteosarcoma, renal and bladder carcinoma, lymphoma, ovarian and cervical cancer and gastric cancer cell lines. Therefore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of these cancers.

[0704] Panel 4D Summary: Ag2502 Ag2502 Highest expression of the CG92715-01 gene is seen in eosinophils (CT=32). Furthermore, differential gene expression is observed in the eosinophil cell line EOL-1 under resting conditions over that in EOL-1 cells stimulated by phorbol ester and ionomycin (CT=34.4). Thus, this gene may be involved in eosinophil function. Antibodies raised against this protein that stimulate its activity may be useful in reduction of eosinophil activation and may therefore be useful therapeutic antibodies for asthma and allergy and as an anti-inflammatory therapeutics for T cell-mediated autoimmune and inflammatory diseases. Low but significant levels of expression are also seen in a cluster of treated and untreated NCI-H292 mucoepidermoid cells adn in normal colon, lung and thymus. This pattern of restricted expression suggests that this gene may be involve in the normal homeostasis of these tissues and/or pathological/inflammatory conditions of the lung.

[0705] P. NOV17a (CG92813-01: Cadherin-related tumor suppressor precursor (FAT))

[0706] Expression of gene CG92813-01 was assessed using the primer-probe sets Ag1350, Ag1413, Ag1414, Ag1515, Ag3085, Ag693, Ag694, Ag740 and Ag3819, described in Tables PA, PB, PC, PD, PE, PF, PG, PH and Pt. Results of the RTQ-PCR runs are shown in Tables PJ, PK, PL, PM, PN, PO, PP, PQ and PR.

TABLE PA
Probe Name Ag1350
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-tggtggcattaatcctgaaata-3′	22	8897	159
Probe	TET-5′-aaaacacttgtccatttgatccctca-3′-TAMRA	26	8848	160
Reverse	5′-tcaggtatttgcaacagatcct-3′	22	8824	161

[0707]

TABLE PB
Probe Name Ag1413
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-aggattctggtgttcctcaaat-3′	22	10908	162
Probe	TET-5′-tcttccacaggaactgtgcatatcaca-3′-TAMRA	27	10931	251
Reverse	5′-cgagactgtgaaggattgtcat-3′	22	10971	163

[0708]

TABLE PC
Probe Name Ag1414
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-gaattctctcaaagccacatga-3′	22	9410	164
Probe	TET-5′-aaccatccctgagagccatagcattg-3′-TAMRA	26	9436	165
Reverse	5′-tgcagaaacagttctgacaatg-3′	22	9466	166

[0709]

TABLE PD
Probe Name Ag1515
			Start	SEQ
			Posi-	ID
Primers	Sequences	Length	tion	No:
Forward	5′-ggatggttccatatcagtgaac	22	2078	167
	-3′
Probe	TET-5′-ctcgtgaccactgggtcct	23	2108	168
	ctgg-3′-TAMRA
Reverse	5′-agaacaatctgggaagcaagtt	22	2145	169
	-3′

[0710]

TABLE PE
Probe Name Ag3085
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-cttcacctgtagctgccca-3′	19	13801	170
Probe	TET-5′-acacgggaaggacctgtgagatggt-3′-TAMRA	25	13827	171
Reverse	5′-acagaggacgccaagacag-3′	19	13858	172

[0711]

TABLE PF
Probe Name Ag693
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-tggtggcattaatcctgaaat-3′	21	8898	173
Probe	TET-5′-aaaacacttgtccatttgatccctca-3′-TAMRA	26	8848	174
Reverse	5′-tcaggtatttgcaacagatcct-3′	22	824	175

[0712]

TABLE PG
Probe Name Ag694
			Start	SEQ
			Posi-	ID
Primers	Sequences	Length	tion	No:
Forward	5′-cggtagatgagaatgctcaagt	22	1614	176
	-3′
Probe	TET-5′-ctcaccgtgacggacgcag	24	1655	177
	attct-3′-TAMRA
Reverse	5′-agaatttgcacggagatgttc	21	1693	178
	-3′

[0713]

TABLE PH
Probe Name Ag740
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-gagggatattgtcagggtcatc-3′	22	14126	179
Probe	TET-5′-aaaagcaacgttctcacttccctttt-3′-TAMRA	26	14100	180
Reverse	5′-aaatcccaaagaggagaagaaa-3′	22	14062	181

[0714]

TABLE PI
Probe Name Ag3819
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-agtcatcaatggctcgcata-3′	20	2523	182
Probe	TET-5′-tcttctggatiataaatgataacagccctg-3′-TAMRA	29	2551	183
Reverse	5′-aagtattggaccgggtagaaga-3′	22	2580	184

[0715]

TABLE PJ
CNS_neurodegeneration_v1.0
	Rel.	Rel.	Rel.		Rel.	Rel.	Rel.
	Exp.(%)	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)	Exp.(%)
	Ag1413,	Ag3819,	Ag693,		Ag1413,	Ag3819,	Ag693,
Tissue	Run	Run	Run	Tissue	Run	Run	Run
Name	206231509	211292463	224758513	Name	206231509	211292463	224758513
AD 1 Hippo	21.0	37.4	25.2	Control	8.6	14.0	11.3
				(Path) 3
				Temporal
				Ctx
AD 2 Hippo	45.1	30.6	34.2	Control	26.2	25.9	5.6
				(Path) 4
				Temporal
				Ctx
AD 3 Hippo	11.0	24.1	8.2	AD 1	9.7	25.5	18.6
				Occipital
				Ctx
AD 4 Hippo	16.3	8.8	10.4	AD 2	0.0	0.0	0.0
				Occipital
				Ctx
				(Missing)
AD 5 hippo	88.3	58.2	15.9	AD 3	12.2	12.6	3.8
				Occipital
				Ctx
AD 6 Hippo	58.6	100.0	67.8	AD 4	28.3	16.7	30.4
				Occipital
				Ctx
Control 2	27.0	45.7	42.6	AD 5	4.3	36.9	39.0
Hippo				Occipital
				Ctx
Control 4	12.9	28.1	3.5	AD 6	45.7	27.0	24.8
Hippo				Occipital
				Ctx
Control	8.7	14.3	19.6	Control 1	14.5	11.1	10.7
(Path) 3				Occipital
Hippo				Ctx
AD 1	10.7	40.6	41.8	Control 2	51.1	34.4	26.6
Temporal				Occipital
Ctx				Ctx
AD 2	69.7	39.5	10.3	Control 3	10.8	21.2	23.3
Temporal				Occipital
Ctx				Ctx
AD 3	10.3	10.0	15.0	Control 4	3.8	17.3	3.4
Temporal				Occipital
Ctx				Ctx
AD 4	23.5	26.1	29.7	Control	100.0	60.3	100.0
Temporal				(Path) 1
Ctx				Occipital
				Ctx
AD 5 Inf	56.3	90.1	52.5	Control	9.2	17.4	25.3
Temporal				(Path) 2
Ctx				Occipital
				Ctx
AD 5 Sup	88.3	67.8	73.2	Control	8.9	14.1	4.5
Temporal				(Path) 3
Ctx				Occipital
				Ctx
AD 6 Inf	66.9	68.8	37.4	Control	23.2	19.9	1.0
Temporal				(Path) 4
Ctx				Occipital
				Ctx
AD 6 Sup	53.2	73.7	67.8	Control 1	10.2	9.8	13.7
Temporal				Parietal
Ctx				Ctx
Control 1	9.6	8.1	8.0	Control 2	47.3	55.1	3.8
Temporal				Parietal
Ctx				Ctx
Control 2	33.4	21.3	25.7	Control 3	10.9	17.4	17.4
Temporal				Parietal
Ctx				Ctx
Control 3	14.5	20.3	11 .8	Control	57.4	55.9	12.7
Temporal				(Path) 1
Ctx				Parietal
				Ctx
Control 4	13.2	10.9	3.1	Control	31.0	26.2	30.4
Temporal				(Path) 2
Ctx				Parietal
				Ctx
Control	50.7	46.0	71.7	Control	6.4	16.5	12.2
(Path) 1				(Path) 3
Temporal				Parietal
Ctx				Ctx
Control	15.5	21.5	27.0	Control	61.6	35.6	5.4
(Path) 2				(Path) 4
Temporal				Parietal
Ctx				Ctx

[0716]

TABLE PK
General_screening_panel_v1.4
	Rel. Exp.(%)	Rel. Exp.(%)		Rel. Exp.(%)	Rel. Exp.(%)
	Ag1413, Run	Ag3819, Run		Ag1413, Run	Ag3819, Run
Tissue Name	213323517	218713598	Tissue Name	213323517	218713598
Adipose	11.3	5.8	Renal ca. TK-10	6.4	4.6
Melanoma*	84.1	68.8	Bladder	6.4	4.5
Hs688(A).T
Melanoma*	29.7	20.7	Gastric ca. (liver	0.9	0.5
Hs688(B).T			met.) NCI-N87
Melanoma*	0.0	0.0	Gastric ca.	0.0	0.0
M14			KATO III
Melanoma*	17.7	14.6	Colon ca. SW-	0.0	0.0
LOXIMVI			948
Melanoma*	0.7	1.2	Colon ca. SW480	0.0	0.0
SK-MEL-5
Squamous	2.2	2.2	Colon ca.*	0.0	0.0
cell			(SW480 met)
carcinoma			SW620
SCC-4
Testis Pool	4.5	4.1	Colon ca. HT29	0.0	0.0
Prostate ca.*	5.0	3.5	Colon ca. HCT-	1.3	1.2
(bone met)			116
PC-3
Prostate Pool	10.6	7.7	Colon ca. CaCo-2	0.1	0.0
Placenta	2.5	3.7	Colon cancer	7.4	4.0
			tissue
Uterus Pool	4.6	5.8	Colon ca.	0.0	0.0
			SW1116
Ovarian ca.	3.6	2.9	Colon ca. Colo-	42.3	0.0
OVCAR-3			205
Ovarian ca.	46.0	7.7	Colon Ca. SW-48	0.0	0.0
SK-OV-3
Ovarian ca.	10.4	7.9	Colon Pool	14.9	11.9
OVCAR-4
Ovarian ca.	5.8	3.7	Small Intestine	17.8	16.6
OVCAR-5			Pool
Ovarian ca.	1.8	1.5	Stomach Pool	48.0	15.0
IGROV-1
Ovarian ca.	3.7	3.3	Bone Marrow	6.3	7.2
OVCAR-8			Pool
Ovary	25.2	13.6	Fetal Heart	12.7	8.0
Breast ca.	0.4	0.2	Heart Pool	7.9	6.8
MCF-7
Breast ca.	54.3	40.1	Lymph Node	21.6	19.1
MDA-MB-			Pool
231
Breast ca. BT	32.5	28.7	Fetal Skeletal	9.7	11.2
549			Muscle
Breast Ca.	7.2	5.6	Skeletal Muscle	5.0	3.9
T47D			Pool
Breast ca.	0.1	0.1	Spleen Pool	14.8	16.3
MDA-N
Breast Pool	48.6	15.9	Thymus Pool	16.3	16.2
Trachea	8.8	11.3	CNS cancer	6.4	6.1
			(glio/astro) U87-
			MG
Lung	6.0	5.9	CNS cancer	48.0	14.8
			(glio/astro) U-
			118-MG
Fetal Lung	70.7	59.5	CNS cancer	50.0	28.3
			(neuro; met) SK-
			N-AS
Lung ca. NCI-	42.9	0.3	CNS cancer	22.7	16.5
N417			(astro) SF-539
Lung ca. LX-1	0.0	0.0	CNS cancer	38.7	38.7
			(astro) SNB-75
Lung ca. NCI-	0.5	0.2	CNS cancer	2.7	2.4
H146			(glio) SNB-19
Lung ca.	2.8	2.5	CNS cancer	27.9	16.8
SHP-77			(glio) SF-295
Lung ca.	1.4	1.7	Brain	7.1	4.1
A549			(Amygdala) Pool
Lung ca. NCI-	0.0	0.0	Brain	0.7	0.5
H526			(cerebellum)
Lung ca. NCI-	100.0	100.0	Brain (fetal)	75.3	52.5
H23
Lung ca. NCI-	44.1	6.5	Brain	7.9	6.2
H460			(Hippocampus)
			Pool
Lung ca.	29.9	20.6	Cerebral Cortex	4.7	4.2
HOP-62			Pool
Lung ca. NCI-	1.1	1.6	Brain (Substantia	4.4	3.2
H522			nigra) Pool
Liver	1.4	0.6	Brain (Thalamus)	9.0	5.4
			Pool
Fetal Liver	16.7	13.5	Brain (whole)	44.4	4.1
Liver ca.	0.4	0.6	Spinal Cord Pool	6.8	4.5
HepG2
Kidney Pool	35.8	24.7	Adrenal Gland	2.3	2.1
Fetal Kidney	48.6	25.7	Pituitary gland	1.2	0.9
			Pool
Renal ca. 786-0	37.6	30.8	Salivary Gland	0.9	0.8
Renal ca.	7.6	6.0	Thyroid (female)	7.8	4.7
A498
Renal ca.	5.6	3.4	Pancreatic ca.	5.3	4.5
ACHN			CAPAN2
Renal ca. UO-	37.4	22.7	Pancreas Pool	20.2	14.0
31

[0717]

TABLE PL
Panel 1.2
	Rel.	Rel.	Rel.		Rel.	Rel.	Rel.
	Exp.(%)	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)	Exp.(%)
	Ag693,	Ag694,	Ag694,		Ag693,	Ag694,	Ag694,
	Run	Run	Run	Tissue	Run	Run	Run
Tissue Name	114253177	114254448	116352614	Name	114253177	114254448	116352614
Endothelial	46.0	42.3	10.5	Renal ca.	0.0	36.1	20.0
cells				786-0
Heart (Fetal)	0.0	10.5	3.3	Renal ca.	0.0	17.6	9.3
				A498
Pancreas	0.0	5.8	5.0	Renal ca.	0.0	0.7	0.5
				RXF 393
Pancreatic ca.	0.0	4.0	2.1	Renal ca.	0.0	6.0	8.2
CAPAN 2				ACHN
Adrenal Gland	0.0	20.6	3.2	Renal ca.	0.0	37.9	15.1
				UO-31
Thyroid	0.0	9.0	9.2	Renal ca.	0.0	12.9	10.2
				TK-10
Salivary gland	0.0	2.6	3.3	Liver	11.0	4.7	7.0
Pituitary gland	0.0	4.5	2.9	Liver (fetal)	0.0	1.5	2.5
Brain (fetal)	100.0	8.9	14.6	Liver ca.	0.0	0.9	0.7
				(hepatoblast)
				HepG2
Brain (whole)	13.3	5.8	4.5	Lung	0.0	2.9	2.9
Brain	14.7	3.7	2.5	Lung (fetal)	0.0	7.8	8.0
(amygdala)
Brain	0.0	2.8	1.3	Lung ca.	0.0	0.0	0.0
(cerebellum)				(small cell)
				LX-1
Brain	81.8	3.7	4.8	Lung ca.	0.0	20.0	6.3
(hippocampus)				(small cell)
				NCI-H69
Brain	0.0	2.2	2.3	Lung ca.	0.0	4.5	1.4
(thalamus)				(s.cell var.)
				SHP-77
Cerebral	10.3	20.6	18.7	Lung ca.	0.0	13.4	9.5
Cortex				(large
				cell) NCI-
				H460
Spinal cord	0.0	3.3	2.9	Lung ca.	0.0	7.1	7.0
				(non-sm.
				cell) A549
glio/astro	0.0	9.5	9.2	Lung ca.	31.6	69.7	76.8
U87-MG				(non-s.cell)
				NCI-H23
glio/astro U-	0.0	22.2	27.2	Lung ca.	0.0	56.3	100.0
118-MG				(non-s.cell)
				HOP-62
astrocytoma	0.0	7.1	6.5	Lung ca.	0.0	6.1	7.1
SW1783				(non-s.cl)
				NCI-H522
neuro*; met	0.0	100.0	94.6	Lung ca.	0.0	11.3	10.0
SK-N-AS				(squam.) SW
				900
astrocytoma	0.0	8.8	9.9	Lung ca.	0.0	25.9	2.9
SF-539				(squam.)
				NCI-H596
astrocytoma	0.0	10.7	9.0	Mammary	0.0	2.6	3.7
SNB-75				gland
glioma SNB-	0.0	16.7	7.9	Breast ca.*	0.0	0.5	0.1
19				(pl.ef) MCF-7
glioma U251	0.0	20.4	9.7	Breast ca.*	0.0	29.3	31.6
				(pl.ef)
				MDA-MB-
				231
glioma SF-295	0.0	16.3	16.6	Breast ca.*	0.0	1.2	2.2
				(pl. ef) T47D
Heart	0.0	21.9	21.2	Breast ca.	0.0	9.7	9.2
				BT-549
Skeletal	0.0	7.5	10.8	Breast ca.	0.0	0.8	0.5
Muscle				MDA-N
Bone marrow	0.0	0.1	0.1	Ovary	0.0	25.2	7.0
Thymus	0.0	0.3	0.1	Ovarian ca.	0.0	6.0	4.5
				OVCAR-3
Spleen	0.0	2.4	2.8	Ovarian ca.	0.0	10.8	8.4
				OVCAR-4
Lymph node	0.0	2.4	2.4	Ovarian ca.	0.0	14.5	13.5
				OVCAR-5
Colorectal	0.0	3.8	1.5	Ovarian ca.	0.0	16.8	7.5
Tissue				OVCAR-8
Stomach	0.0	4.6	5.2	Ovarian ca.	0.0	6.1	3.7
				IGROV-1
Small intestine	0.0	5.6	6.0	Ovarian ca.	0.0	12.9	9.9
				(ascites) SK-
				OV-3
Colon ca.	0.0	0.0	0.0	Uterus	0.0	2.4	2.8
SW480
Colon ca.*	0.0	0.0	0.0	Placenta	0.0	5.9	9.2
SW620
(SW480 met)
Colon ca.	0.0	0.5	0.6	Prostate	0.0	1.1	1.2
HT29
Colon ca.	0.0	1.7	1.2	Prostate ca.*	0.0	9.5	5.4
HCT-116				(bone met)
				PC-3
Colon ca.	0.0	0.1	0.2	Testis	0.0	2.3	2.8
CaCo-2
Colon ca.	0.0	3.9	2.5	Melanoma	0.0	19.6	25.7
Tissue				Hs688(A).T
(ODO3866)
Colon ca.	0.0	0.7	1.0	Melanoma*	0.0	9.7	11.3
HCC-2998				(met)
				Hs688(B).T
Gastric ca.*	0.0	0.8	1.2	Melanoma	0.0	1.0	0.5
(liver met)				UACC-62
NCI-N87
Bladder	18.7	16.4	15.3	Melanoma	0.0	0.2	0.0
				M14
Trachea	0.0	1.2	2.5	Melanoma	0.0	13.6	9.5
				LOX IMVI
Kidney	0.0	25.0	11.0	Melanoma*	0.0	1.4	1.8
				(met) SK-
				MEL-5
Kidney (fetal)	0.0	20.7	32.3

[0718]

TABLE PM
Panel 1.3D
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag3085,		Ag3085,
	Run		Run
Tissue Name	165673584	Tissue Name	165673584
Liver adenocarcinoma	5.6	Kidney (fetal)	22.2
Pancreas	3.0	Renal ca. 786-0	28.3
Pancreatic ca.	3.5	Renal ca. A498	25.7
CAPAN 2
Adrenal gland	2.8	Renal ca. RXF 393	0.0
Thyroid	11.3	Renal ca. ACHN	3.7
Salivary gland	1.7	Renal ca. UO-31	64.2
Pituitary gland	6.8	Renal ca. TK-10	1.6
Brain (fetal)	100.0	Liver	5.5
Brain (whole)	23.2	Liver (fetal)	6.3
Brain (amygdala)	13.1	Liver ca.	0.5
		(hepatoblast) HepG2
Brain (cerebellum)	2.4	Lung	27.9
Brain (hippocampus)	17.6	Lung (fetal)	21.0
Brain	11.5	Lung ca. (small cell)	0.0
(substantia nigra)		LX-1
Brain (thalamus)	15.9	Lung ca. (small cell)	0.0
		NCI-H69
Cerebral Cortex	4.4	Lung ca.	1.4
		(s.cell var.)
		SHP-77
Spinal cord	12.0	Lung ca. (large	9.0
		cell) NCI-H460
glio/astro U87-MG	5.5	Lung ca. (non-sm.	1.2
		cell) A549
glio/astro U-118-MG	49.3	Lung ca.	40.3
		(non-s.cell)
		NCI-H23
astrocytoma SW1783	21.0	Lung ca.	53.6
		(non-s.cell)
		HOP-62
neuro*; met SK-N-AS	75.8	Lung ca. (non-s.cl)	0.7
		NCI-H522
astrocytoma SF-539	11.4	Lung ca. (squam.)	4.9
		SW 900
astrocytoma SNB-75	27.9	Lung ca. (squam.)	0.0
		NCI-H596
glioma SNB-19	4.4	Mammary gland	25.2
glioma U251	42.0	Breast ca.* (pl.ef)	0.0
		MCF-7
glioma SF-295	12.6	Breast ca.* (pl.ef)	68.3
		MDA-MB-231
Heart (fetal)	3.5	Breast ca.* (pl.ef)	0.0
		T47D
Heart	10.4	Breast ca. BT-549	14.2
Skeletal muscle (fetal)	7.0	Breast ca. MDA-N	0.0
Skeletal muscle	12.1	Ovary	5.6
Bone marrow	1.1	Ovarian ca.	3.7
		OVCAR-3
Thymus	1.8	Ovarian ca.	6.6
		OVCAR-4
Spleen	14.0	Ovarian ca.	0.9
		OVCAR-5
Lymph node	7.2	Ovarian ca.	4.6
		OVCAR-8
Colorectal	24.8	Ovarian ca.	0.0
		IGROV-1
Stomach	22.5	Ovarian ca.*	7.7
		(ascites) SK-OV-3
Small intestine	35.6	Uterus	25.7
Colon ca. SW480	0.0	Placenta	6.9
Colon ca.*	0.8	Prostate	4.5
SW620 (SW480 met)
Colon ca. HT29	0.0	Prostate ca.* (bone	3.5
		met) PC-3
Colon ca. HCT-116	0.5	Testis	3.8
Colon ca. CaCo-2	0.6	Melanoma	26.1
		Hs688(A).T
Colon ca.	7.3	Melanoma* (met)	9.2
tissue (ODO3866)		Hs688(B).T
Colon ca. HCC-2998	1.1	Melanoma UACC-	0.8
		62
Gastric ca.* (liver met)	0.5	Melanoma M14	0.9
NCI-N87
Bladder	4.3	Melanoma LOX	1.6
		IMVI
Trachea	4.5	Melanoma* (met)	0.0
		SK-MEL-5
Kidney	10.3	Adipose	20.7

[0719]

TABLE PN
Panel 2.2
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag3085, Run		Ag3085, Run
Tissue Name	174284805	Tissue Name	174284805
Normal Colon	47.0	Kidney Margin	84.1
		(OD04348)
Colon cancer	19.1	Kidney malignant	1.4
(OD06064)		cancer (OD06204B)
Colon Margin	34.9	Kidney normal adjacent	10.8
(OD06064)		tissue (OD06204E)
Colon cancer	5.8	Kidney Cancer	15.4
(OD06159)		(OD04450-01)
Colon Margin	37.6	Kidney Margin	19.8
(OD06159)		(OD04450-03)
Colon cancer	15.6	Kidney Cancer	0.0
(OD06297-04)		8120613
Colon Margin	76.8	Kidney Margin	6.3
(OD06297-05)		8120614
CC Gr.2 ascend colon	15.8	Kidney Cancer	5.2
(ODO3921)		9010320
CC Margin (ODO3921)	20.3	Kidney Margin	0.7
		9010321
Colon cancer metastasis	1.5	Kidney Cancer	4.8
(OD06104)		8120607
Lung Margin	11.4	Kidney Margin	1.0
(OD06104)		8120608
Colon mets to lung	17.6	Normal Uterus	100.0
(OD04451-01)
Lung Margin	48.3	Uterine Cancer 064011	16.6
(OD04451-02)
Normal Prostate	5.0	Normal Thyroid	8.8
Prostate Cancer	3.8	Thyroid Cancer 064010	9.7
(OD04410)
Prostate Margin	24.3	Thyroid Cancer	21.3
(OD04410)		A302152
Normal Ovary	20.0	Thyroid Margin	32.1
		A302153
Ovarian cancer	4.7	Normal Breast	36.6
(OD06283-03)
Ovarian Margin	43.8	Breast Cancer	0.0
(OD06283-07)		(OD04566)
Ovarian Cancer 064008	19.2	Breast Cancer 1024	15.4
Ovarian cancer	4.5	Breast Cancer	16.0
(OD06145)		(OD04590-01)
Ovarian Margin	30.8	Breast Cancer Mets	21.2
(OD06145)		(OD04590-03)
Ovarian cancer	3.3	Breast Cancer	8.5
(OD06455-03)		Metastasis (OD04655-05)
Ovarian Margin	41.2	Breast Cancer 064006	6.5
(OD06455-07)
Normal Lung	26.8	Breast Cancer 9100266	6.1
Invasive poor diff. lung	0.9	Breast Margin 9100265	10.8
adeno (ODO4945-01
Lung Margin	38.2	Breast Cancer A209073	3.3
(ODO4945-03)
Lung Malignant Cancer	12.5	Breast Margin	21.0
(OD03126)		A2090734
Lung Margin	12.4	Breast cancer	11.7
(OD03126)		(OD06083)
Lung Cancer	10.3	Breast cancer node	5.4
(OD05014A)		metastasis (OD06083)
Lung Margin	19.9	Normal Liver	27.7
(OD05014B)
Lung cancer (OD06081)	4.5	Liver Cancer 1026	1.6
Lung Margin	27.2	Liver Cancer 1025	16.0
(OD06081)
Lung Cancer	0.0	Liver Cancer 6004-T	12.2
(OD04237-01)
Lung Margin	84.1	Liver Tissue 6004-N	2.2
(OD04237-02)
Ocular Melanoma	1.4	Liver Cancer 6005-T	8.8
Metastasis
Ocular Melanoma	10.4	Liver Tissue 6005-N	27.7
Margin (Liver)
Melanoma Metastasis	1.2	Liver Cancer 064003	25.0
Melanoma Margin	53.6	Normal Bladder	8.0
(Lung)
Normal Kidney	31.4	Bladder Cancer 1023	0.0
Kidney Ca, Nuclear	65.1	Bladder Cancer	5.4
grade 2 (OD04338)		A302173
Kidney Margin	13.8	Normal Stomach	87.1
(OD04338)
Kidney Ca Nuclear	35.1	Gastric Cancer	8.2
grade 1/2 (OD04339)		9060397
Kidney Margin	24.5	Stomach Margin	5.0
(OD04339)		9060396
Kidney Ca, Clear cell	16.7	Gastric Cancer	23.0
type (OD04340)		9060395
Kidney Margin	37.6	Stomach Margin	27.2
(OD04340)		9060394
Kidney Ca, Nuclear	2.1	Gastric Cancer 064005	6.8
grade 3 (OD04348)

[0720]

TABLE PO
Panel 2D
	Rel. Exp.(%)	Rel. Exp.(%)		Rel. Exp.(%)	Rel. Exp.(%)
	Ag1413, Run	Ag740, Run		Ag1413, Run	Ag740, Run
Tissue Name	169477489	169590466	Tissue Name	169477489	169590466
Normal Colon	68.3	100.0	Kidney	2.9	1.0
			Margin
			8120608
CC Well to Mod	6.3	5.0	Kidney	0.2	0.5
Diff (ODO3866)			Cancer
			8120613
CC Margin	7.9	25.7	Kidney	6.3	2.0
(ODO3866)			Margin
			8120614
CC Gr.2	4.6	12.6	Kidney	23.0	2.4
rectosigmoid			Cancer
(ODO3868)			9010320
CC Margin	11.0	38.2	Kidney	11.7	1.7
(ODO3868)			Margin
			9010321
CC Mod Diff	1.4	9.7	Normal Uterus	13.8	4.6
(ODO3920)
CC Margin	12.1	54.3	Uterus Cancer	17.8	9.3
(ODO3920)			064011
CC Gr.2 ascend	20.3	61.6	Normal	13.6	10.4
colon			Thyroid
(ODO3921)
CC Margin	10.9	12.9	Thyroid	12.9	6.4
(ODO3921)			Cancer
			064010
CC from Partial	4.9	3.3	Thyroid	8.1	5.4
Hepatectomy			Cancer
(ODO4309)			A302152
Mets
Liver Margin	10.4	9.0	Thyroid	29.1	11.0
(ODO4309)			Margin
			A302153
Colon mets to	2.9	1.4	Normal Breast	21.0	13.5
lung (OD04451-
01)
Lung Margin	10.2	11.5	Breast Cancer	1.8	1.2
(OD04451-02)			(OD04566)
Normal Prostate	2.7	5.1	Breast Cancer	17.3	1.1
6546-1			(OD04590-01)
Prostate Cancer	18.4	12.2	Breast Cancer	23.3	3.7
(OD04410)			Mets
			(OD04590-03)
Prostate Margin	36.1	44.4	Breast Cancer	4.2	0.8
(OD04410)			Metastasis
			(OD04655-05)
Prostate Cancer	17.3	28.9	Breast Cancer	5.2	3.9
(OD04720-01)			064006
Prostate Margin	28.5	39.5	Breast Cancer	12.8	1.8
(OD04720-02)			1024
Normal Lung	48.0	38.4	Breast Cancer	3.9	1.7
061010			9100266
Lung Met to	3.6	3.0	Breast Margin	10.2	5.0
Muscle			9100265
(ODO4286)
Muscle Margin	5.9	3.5	Breast Cancer	12.2	10.1
(ODO4286)			A209073
Lung Malignant	11.7	9.7	Breast Margin	11.7	9.0
Cancer			A209073
(OD03126)
Lung Margin	40.3	24.7	Normal Liver	7.1	4.4
(OD03126)
Lung Cancer	18.0	2.7	Liver Cancer	10.3	8.0
(OD04404)			064003
Lung Margin	32.8	9.0	Liver Cancer	5.0	5.1
(OD04404)			1025
Lung Cancer	2.9	2.7	Liver Cancer	3.0	1.5
(OD04565)			1026
Lung Margin	8.0	10.2	Liver Cancer	5.4	0.7
(OD04565)			6004-T
Lung Cancer	4.5	4.0	Liver Tissue	1.4	0.3
(OD04237-01)			6004-N
Lung Margin	31.4	17.9	Liver Cancer	5.2	0.5
(OD04237-02)			6005-T
Ocular Mel Met	0.9	0.3	Liver Tissue	3.3	3.5
to Liver			6005-N
(ODO4310)
Liver Margin	8.1	10.8	Normal	7.1	7.7
(ODO4310)			Bladder
Melanoma Mets	2.8	1.5	Bladder	1.0	4.1
to Lung			Cancer 1023
(OD04321)
Lung Margin	33.9	19.2	Bladder	3.0	3.6
(OD04321)			Cancer
			A302173
Normal Kidney	100.0	28.5	Bladder	6.0	4.4
			Cancer
			(OD04718-01)
Kidney Ca,	14.1	9.8	Bladder	27.5	25.2
Nuclear grade 2			Normal
(OD04338)			Adjacent
			(OD04718-03)
Kidney Margin	24.0	7.1	Normal Ovary	6.7	4.8
(OD04338)
Kidney Ca	14.3	6.7	Ovarian	27.0	21.9
Nuclear grade			Cancer
1/2 (OD04339)			064008
Kidney Margin	22.8	4.5	Ovarian	0.7	0.2
(OD04339)			Cancer
			(OD04768-07)
Kidney Ca, Clear	53.2	16.0	Ovary Margin	12.4	6.7
cell type			(OD04768-08)
(OD04340)
Kidney Margin	26.6	10.5	Normal	27.4	12.3
(OD04340)			Stomach
Kidney Ca,	8.9	3.6	Gastric Cancer	6.9	2.1
Nuclear grade 3			9060358
(OD04348)
Kidney Margin	14.1	10.0	Stomach	7.2	10.9
(OD04348)			Margin
			9060359
Kidney Cancer	27.4	27.4	Gastric Cancer	29.9	21.0
(OD04622-01)			9060395
Kidney Margin	3.5	4.4	Stomach	13.7	16.3
(OD04622-03)			Margin
			9060394
Kidney Cancer	8.4	2.6	Gastric Cancer	23.2	18.3
(OD04450-01)			9060397
Kidney Margin	23.8	7.5	Stomach	3.7	2.6
(OD04450-03)			Margin
			9060396
Kidney Cancer	1.3	0.4	Gastric Cancer	18.3	26.8
8120607			064005

[0721]

TABLE PP
Panel 4.1D
	Rel.	Rel.	Rel.		Rel.	Rel.	Rel.
	Exp.(%)	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)	Exp.(%)
	Ag1413,	Ag3819,	Ag740,		Ag1413,	Ag3819,	Ag740,
	Run	Run	Run		Run	Run	Run
Tissue Name	169827815	170127253	169827863	Tissue Name	169827815	170127253	169827863
Secondary Th1 act	0.0	0.1	0.0	HUVEC IL-	21.3	24.5	21.2
				1beta
Secondary Th2 act	0.0	0.0	0.0	HUVEC IFN	100.0	100.0	100.0
				gamma
Secondary Tr1 act	0.0	0.1	0.0	HUVEC TNF	10.0	19.2	11.8
				alpha + IFN
				gamma
Secondary Th1	0.0	0.1	0.0	HUVEC TNF	4.0	5.2	3.1
rest				alpha + IL4
Secondary Th2	0.2	0 0	0.0	HUVEC IL-11	22.5	29.5	28.1
rest
Secondary Tr1	0.0	0.1	0.0	Lung	48.6	91.4	59.5
rest				Microvascular
				EC none
Primary Th1 act	0.0	0.0	0.0	Lung	12.5	18.8	8.6
				Microvascular
				EC TNF alpha +
				IL-1beta
Primary Th2 act	0.0	0.0	0.0	Microvascular	62.9	58.6	62.4
				Dermal EC none
Primary Tr1 act	0.0	0.0	0.0	Microvasular	8.8	9.9	9.7
				Dermal EC
				TNF alpha + IL-
				1beta
Primary Th1 rest	0.0	0.0	0.0	Bronchial	3.8	4.2	2.7
				epithelium
				TNF alpha +
				IL1beta
Primary Th2 rest	0.0	0.0	0.0	Small airway	1.8	2.1	1.2
				epithelium none
Primary Tr1 rest	0.0	0.0	0.0	Small airway	3.4	1.9	2.5
				epithelium
				TNF alpha + IL-
				1beta
CD45RA CD4	3.4	4.1	3.0	Coronery artery	4.2	3.4	4.4
lymphocyte act				SMC rest
CD45RO CD4	0.0	0.0	0.0	Coronery artery	2.0	3.3	4.1
lymphocyte act				SMC TNF
				alpha + IL-1beta
CD8 lymphocyte	0.0	0.0	0.0	Astrocytes rest	7.0	6.3	6.0
act
Secondary CD8	0.0	0.0	0.0	Astrocytes	3.7	4.2	6.5
lymphocyte rest				TNF alpha + IL-
				1beta
Secondary CD8	0.0	0.0	0.0	KU-812	1.1	1.5	2.0
lymphocyte act				(Basophil) rest
CD4 lymphocyte	0.2	0.1	0.0	KU-812	4.2	3.9	4.9
none				(Basophil)
				PMA/ionomycin
2ry	0.1	0.0	0.0	CCD1106	1.0	3.0	1.7
Th1/Th2/Tr1_anti-				(Keratinocytes)
CD95 CH11				none
LAK cells rest	0.3	0.0	0.0	CCD1106	1.6	1.3	0.0
				(Keratinocytes)
				TNF alpha + IL-
				1beta
LAK cells IL-2	0.5	0.5	0.0	Liver cirrhosis	4.5	7.0	6.4
LAK cells IL-	0.0	0.1	0.0	NCI-H292 none	0.3	0.9	1.1
2 + IL-12
LAK cells IL-	0.1	0.3	0.0	NCI-H292 IL-4	0.9	1.3	2.3
2 + IFN gamma
LAK cells IL-2 +	0.5	0.2	0.0	NCI-H292 IL-9	2.0	2.9	2.8
IL-18
LAK cells	0.1	0.1	0.0	NCI-H292 IL-	1.1	1.0	1.5
PMA/ionomycin				13
NK Cells IL-2 rest	3.3	2.4	2.2	NCI-H292 IFN	2.6	2.3	4.2
				gamma
Two Way MLR 3	0.7	0.3	0.0	HPAEC none	27.0	41.5	52.9
day
Two Way MLR 5	0.0	0.1	0.0	HPAEC TNF	6.0	7.0	4.0
day				alpha + IL-1beta
Two Way MLR 7	0.0	0.0	0.0	Lung fibroblast	10.2	14.4	6.7
day				none
PBMC rest	0.2	0.2	0.0	Lung fibroblast	11.6	10.8	8.9
				TNF alpha + IL-
				1beta
PBMC PWM	0.1	0.0	0.0	Lung fibroblast	9.1	13.9	4.2
				IL-4
PBMC PHA-L	0.1	0.0	0.0	Lung fibroblast	17.3	26.4	12.2
				IL-9
Ramos (B cell)	0.0	0.0	0.0	Lung fibroblast	6.3	13.2	5.4
none				IL-13
Ramos (B cell)	0.0	0.0	0.0	Lung fibroblast	11.2	9.4	6.6
ionomycin				IFN gamma
B lymphocytes	0.0	0.0	0.0	Dermal	11.1	15.9	23.2
PWM				fibroblast
				CCD1070 rest
B lymphocytes	0.0	0.2	0.0	Dermal	4.6	6.3	6.3
CD40L and IL-4				fibroblast
				CCD1070 TNF
				alpha
EOL-1 dbcAMP	0.0	0.0	0.0	Dermal	2.1	3.4	5.9
				fibroblast
				CCD1070 IL-1
				beta
EOL-1 dbcAMP	0.0	0.0	0.0	Dermal	6.9	8.4	4.7
PMA/ionomycin				fibroblast IFN
				gamma
Dendritic cells	0.0	0.0	0.0	Dermal	15.5	17.2	21.8
none				fibroblast IL-4
Dendritic cells	0.0	0.0	0.0	Dermal	17.6	14.0	12.8
LPS				Fibroblasts rest
Dendritic cells	0.2	0.0	0.0	Neutrophils	0.0	0.0	0.0
anti-CD40				TNFa+LPS
Monocytes rest	0.0	0.0	0.0	Neutrophils rest	0.0	0.0	0.0
Monocytes LPS	0.0	0.0	0.0	Colon	6.0	5.2	5.5
Macrophages rest	0.0	0.0	0.0	Lung	17.1	15.1	25.3
Macrophages LPS	0.0	0.0	0.0	Thymus	3.6	2.6	5.3
HUVEC none	16.2	17.9	19.5	Kidney	11.4	12.1	14.9
HUVEC starved	37.1	38.7	49.0

[0722]

TABLE PQ
Panel 4D
	Rel.	Rel.		Rel.	Rel.
	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)
	Ag1515,	Ag3085,		Ag1515,	Ag3085,
	Run	Run		Run	Run
Tissue Name	163478545	164682194	Tissue Name	163478545	164682194
Secondary Th1 act	0.0	0.0	HUVEC IL-1beta	17.8	8.5
Secondary Th2 act	0.0	0.0	HUVEC IFN	100.0	100.0
			gamma
Secondary Tr1 act	0.0	0.2	HUVEC TNF	18.2	16.2
			alpha + IFN
			gamma
Secondary Th1 rest	0.1	0.0	HUVEC TNF	5.4	4.2
			alpha + IL4
Secondary Th2 rest	0.0	0.0	HUVEC IL-11	31.4	35.1
Secondary Tr1 rest	0.0	0.2	Lung	50.3	50.7
			Microvascular EC
			none
Primary Th1 act	0.0	0.0	Lung	9.0	6.8
			Microvascular EC
			TNF alpha + IL-
			1beta
Primary Th2 act	0.0	0.0	Microvascular	71.7	83.5
			Dermal EC none
Primary Tr1 act	0.0	0.0	Microsvasular	16.2	14.1
			Dermal EC
			TNF alpha + IL-
			1beta
Primary Th1 rest	0.0	0.0	Bronchial	6.7	5.6
			epithelium
			TNF alpha +
			IL1beta
Primary Th2 rest	0.0	0.0	Small airway	2.0	2.1
			epithelium none
Primary Tr1 rest	0.0	0.0	Small airway	12.9	8.8
			epithelium
			TNF alpha + IL-
			1beta
CD45RA CD4	3.8	4.6	Coronery artery	5.4	4.8
lymphocyte act			SMC rest
CD45RO CD4	0.0	0.3	Coronery artery	2.2	2.6
lymphocyte act			SMC TNF
			alpha + IL-1beta
CD8 lymphocyte	0.1	0.0	Astrocytes rest	5.1	8.9
act
Secondary CD8	0.0	0.0	Astrocytes	5.8	5.8
lymphocyte rest			TNF alpha + IL-
			1beta
Secondary CD8	0.0	0.0	KU-812	1.2	0.7
lymphocyte act			(Basophil) rest
CD4 lymphocyte	0.0	0.0	KU-812	6.7	4.7
none			(Basophil)
			PMA/ionomycin
2ry	0.1	0.0	CCD1106	2.0	4.4
Th1/Th2/Tr1_anti-			(Keratinocytes)
CD95 CH11			none
LAK cells rest	0.3	0.1	CCD1106	1.1	0.7
			(Keratinocytes)
			TNF alpha + IL-
			1beta
LAK cells IL-2	0.5	0.4	Liver cirrhosis	4.8	4.9
LAK cells IL-	0.3	0.2	Lupus kidney	1.9	4.7
2 + IL-12
LAK cells IL-	0.4	0.4	NCI-H292 none	2.1	1.5
2 + IFN gamma
LAK cells IL-2 +	0.5	0.0	NCI-H292 IL-4	3.1	2.3
IL-18
LAK cells	0.0	0.4	NCI-H292 IL-9	3.7	3.1
PMA/ionomycin
NK Cells IL-2 rest	2.2	1.8	NCI-H292 IL-13	1.5	1.7
Two Way MLR 3	0.4	0.5	NCI-H292 IFN	3.6	1.6
day			gamma
Two Way MLR 5	0.1	0.1	HPAEC none	29.3	40.1
day
Two Way MLR 7	0.1	0.0	HPAEC TNF	4.5	5.3
day			alpha + IL-1beta
PBMC rest	0.4	0.6	Lung fibroblast	12.7	19.1
			none
PBMC PWM	0.4	0.0	Lung fibroblast	10.0	15.3
			TNF alpha + IL-1
			beta
PBMC PHA-L	0.1	0.1	Lung fibroblast	16.4	20.2
			IL-4
Ramos (B cell)	0.0	0.0	Lung fibroblast	19.1	21.5
none			IL-9
Ramos (B cell)	0.0	0.0	Lung fibroblast	7.5	14.5
ionomycin			IL-13
B lymphocytes	0.0	0.0	Lung fibroblast	17.2	19.6
PWM			IFN gamma
B lymphocytes	0.1	0.0	Dermal fibroblast	30.6	27.0
CD40L and IL-4			CCD1070 rest
EOL-1 dbcAMP	0.0	0.0	Dermal fibroblast	8.4	10.1
			CCD1070 TNF
			alpha
EOL-1 dbcAMP	0.0	0.0	Dermal fibroblast	6.5	8.5
PMA/ionomycin			CCD1070 IL-1
			beta
Dendritic cells	0.0	0.0	Dermal fibroblast	7.0	11.0
none			IFN gamma
Dendritic cells LPS	0.0	0.0	Dermal fibroblast	17.6	15.7
			IL-4
Dendritic cells anti-	0.0	0.0	IBD Colitis 2	0.5	2.2
CD40
Monocytes rest	0.0	0.0	IBD Crohn's	1.8	3.0
Monocytes LPS	0.0	0.0	Colon	14.6	15.6
Macrophages rest	0.0	0.1	Lung	17.9	21.0
Macrophages LPS	0.0	0.0	Thymus	22.1	22.2
HUVEC none	22.8	30.4	Kidney	6.7	5.2
HUVEC starved	97.9	88.9

[0723]

TABLE PR
Panel CNS_1
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag693, Run		Ag693, Run
Tissue Name	171791037	Tissue Name	171791037
BA4 Control	10.2	BA17 PSP	13.5
BA4 Control2	53.6	BA17 PSP2	4.5
BA4	5.0	Sub Nigra Control	58.6
Alzheimer's2
BA4 Parkinson's	40.3	Sub Nigra Control2	47.0
BA4	59.5	Sub Nigra	14.3
Parkinson's2		Alzheimer's2
BA4	19.5	Sub Nigra	71.7
Huntington's		Parkinson's2
BA4	5.0	Sub Nigra	80.7
Huntington's2		Huntington's
BA4 PSP	11.0	Sub Nigra	92.0
		Huntington's2
BA4 PSP2	13.1	Sub Nigra PSP2	31.2
BA4 Depression	15.7	Sub Nigra	35.4
		Depression
BA4	5.7	Sub Nigra	15.6
Depression2		Depression2
BA7 Control	32.5	Glob Palladus	37.6
		Control
BA7 Control2	16.8	Glob Palladus	6.3
		Control2
BA7	9.6	Glob Palladus	9.2
Alzheimer's2		Alzheimer's
BA7 Parkinson's	14.8	Glob Palladus	10.3
		Alzheimer's2
BA7	39.5	Glob Palladus	91.4
Parkinson's2		Parkinson's
BA7	46.0	Glob Palladus	39.5
Huntington's		Parkinson's2
BA7	54.7	Glob Palladus PSP	5.1
Huntington's2
BA7 PSP	36.3	Glob Palladus PSP2	2.4
BA7 PSP2	14.2	Glob Palladus	11.5
		Depression
BA7 Depression	10.6	Temp Pole Control	6.6
BA9 Control	12.9	Temp Pole Control2	29.1
BA9 Control2	81.2	Temp Pole	9.7
		Alzheimer's
BA9 Alzheimer's	5.3	Temp Pole	4.8
		Alzheimer's2
BA9	12.2	Temp Pole	39.8
Alzheimer's2		Parkinson's
BA9 Parkinson's	36.1	Temp Pole	19.5
		Parkinson's2
BA9	35.1	Temp Pole	46.3
Parkinson's2		Huntington's
BA9	40.6	Temp Pole PSP	5.9
Huntington's
BA9	18.2	Temp Pole PSP2	3.4
Huntington's2
BA9 PSP	7.3	Temp Pole	6.3
		Depression2
BA9 PSP2	7.7	Cing Gyr Control	43.8
BA9 Depression	10.4	Cing Gyr Control2	19.1
BA9	5.1	Cing Gyr	20.9
Depression2		Alzheimer's
BA17 Control	36.6	Cing Gyr	7.7
		Alzheimer's2
BA17 Control2	47.0	Cing Gyr Parkinson's	40.1
BA17	8.2	Cing Gyr	49.0
Alzheimer's2		Parkinson's2
BA17	45.4	Cing Gyr	100.0
Parkinson's		Huntington's
BA17	43.2	Cing Gyr	56.6
Parkinson's2		Huntington's2
BA17	39.8	Cing Gyr PSP	22.2
Huntington's
BA17	17.1	Cing Gyr PSP2	10.2
Huntington's2
BA17	44.1	Cing Gyr Depression	23.8
Depression
BA17	26.6	Cing Gyr	23.0
Depression2		Depression2

[0724] CNS_neurodegeneration_v1.0 Summary: Ag1413/Ag3819/Ag693 Three experiment with different primer and probe sets are in excellent agreement. This panel confirms the expression of the CG92813-01 gene at low levels in the brain in 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. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.

[0725] General_screening_panel_v1.4 Summary: Ag]413/Ag3819 Two experiment with different primer and probe sets are in excellent agreement, with highest expression of the CG92813-01 gene in lung cancer cell line NCI-H23 (CT=26-28). High to moderate levels of expression of this gene is also seen in cluster of CNS cancer, renal cancer, lung cancer, breast cancer, ovarian cancer and melanoma 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 ovarian cancer. The CG92813-01 gene codes for cadherin-related tumor suppressor precursor. E-cadherin, a related protein is used as a prognostic marker for breast cancer detection (Ref. 1). Therefore, expression of CG92813-01 gene can also be used as diagnostic marker in the above mentioned cancers.

[0726] 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. In addition, E cadherin, a related protein is shown to be reduced in small intestinal mucosa of coeliac sprue disease (Ref. 1), a sample not used in this panel. In analogy to E cadherin, we predict that expression of the CG92813-01 gene may also be reduced in this tissue of coeliac sprue disease. Coeliac sprue is a chronic disease, in which there is a characteristic mucosal lesion of the small intestine and impaired nutrient absorption, which improves upon the withdrawal of wheat gliadins and related grain proteins from the diet. Biopsy specimens demonstrate diffuse enteritis with pronounced atrophy or total loss of villi. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of coelic sprue disease.

[0727] In addition, this gene is expressed at low to moderate levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. This gene product is a transmembrane glycoproteins belonging to the cadherin superfamily of molecules, which are involved in many biological processes such as cell adhesion, cytoskeletal organization and morphogenesis. Cadherins can act as axon guidance and cell adhesion proteins, specifically during development and in the response to injury (ref 2). Therefore, manipulation of levels of this protein may be of use in inducing a compensatory synaptogenic response to neuronal death in Alzheimer's disease, Parkinson's disease, Huntington's disease, spinocerebellar ataxia, progressive supranuclear palsy, ALS, head trauma, stroke, or any other disease/condition associated with neuronal loss.

[0728] Ag740 Results from one experiment with this gene are not included. The amp plot indicates that there were experimental difficulties with this run.

[0729] See, generally,

[0730] Barshack I, Goldberg I, Chowers Y, Weiss B, Horowitz A, Kopolovic J. (2001) Immunohistochemical analysis of candidate gene product expression in the duodenal epithelium of children with coeliac sprue. J Clin Pathol 54(9):684-8. PMID: 11533074 Ranscht B. (2000) Cadherins: molecular codes for axon guidance and synapse formation. Int. J. Dev. Neurosci. 18: 643-651. PMID: 10978842

[0731] Panel 1.2 Summary: Ag694 Two experiment with same primer and probe sets are in excellent agreement, with high expression of the CG92813-01 gene in neuroblastoma metastasis SK-N-AS, and two of the lung cancer (NCI-H23, HOP-62) cell lines (CT=26-28). High to moderate levels of expression of this gene is also seen in cluster of CNS cancer, renal cancer, lung cancer, breast cancer, ovarian cancer and melanoma cell lines. Significant expression of this gene is also seen in tissues with metabolic or endocrine function and all regions of the central nervous system examined. Please see Panel 1.4 for a discussion of the potential utility of this gene.

[0732] Ag693 Highest expression of this gene is detected in fetal brain (CT=28.5). Expression of this gene is restricted to some of the brain region, endothelial cells, bladder, liver, and a lung cancer NCI-H23 cell line (CTs=28-32). Thus, expression of this gene can be used to distinguish these samples from other samples used in this panel. Please note that this primer and probe set recognizes a different region of the gene and shows a different expression pattern.

[0733] Panel 1.3D Summary: Ag3085 Highest expression of the CG92813-01 gene is detected in fetal brain (CT=28). High to moderate levels of expression of this gene is also seen in cluster of CNS cancer, renal cancer, lung cancer, breast cancer, ovarian cancer and melanoma cell lines. Significant expression of this gene is also seen in tissues with metabolic or endocrine function and all regions of the central nervous system examined. Please see Panel 1.4 for a discussion of the potential utility of this gene.

[0734] Panel 2.2 Summary: Ag3085 Highest expression of the CG92813-01 gene is detected in normal uterus (CT=30). High to moderate levels of expression of this gene is also seen in both normal and cancer tissues. Interestingly, expression of this gene is higher in control margin samples of colon, ovary, lung (OD04237-02), liver (ODO4310), kidney (OD04348; 8120614) as compared to their corresponding cancer tissue. Please see Panel 1.4 for a discussion of the potential utility of this gene.

[0735] Panel 2D Summary: Ag1413/Ag740 Highest expression of the CG92813-01 gene is detected in normal Kidney and colon (CTs=29-30). Two experiments with different primer and probe sets are in good agreement, with significant expression of this gene in both normal and cancer tissues. Interestingly, expression of this gene is higher in control margin samples of colon (ODO3920), liver (ODO43 10), and ovary (0D04768-08) as compared to their corresponding cancer tissue. Please see Panel 1.4 for a discussion of the potential utility of this gene.

[0736] Panel 4.1D Summary: Ag1413/Ag3819/Ag740 Three experiments with different probe and primer sets are in excellent agreement, with highest expression of the CG92813-01 gene in IFN gamma treated HUVEC cells (CT=25-27). In addition, high to moderate expression of this gene is seen in treated and untreated HUVEC, lung microvascular EC, microvascular dermal EC, Bronchial epithelium, small airway epithelium, NCI-H292, HPAEC, lung fibroblasts, and dermal fibroblasts. The expression of this gene in cells derived from or within the lung suggests that this gene may be involved in normal conditions as well as pathological and inflammatory lung disorders that include chronic obstructive pulmonary disease, asthma, allergy and emphysema.

[0737] In addition, high expression of this gene is also detected in normal tissues represented by colon, lung, thymus and kidney. Therefore, therapeutic modulation of the activity of the protein encoded by this gene may be useful in the treatment of inflammatory disease affecting these tissues such as inflammatory bowel disease, chronic obstructive pulmonary disease, asthma, allergy, emphysema, lupus and glomerulonephritis.

[0738] Panel 4D Summary: Ag1515/Ag3085 Two experiments with different probe and primer sets are in excellent agreement, with highest expression of the CG92813-01 gene in IFN gamma treated HUVEC cells (CT=25-27). In addition, high to moderate expression of this gene is seen in treated and untreated HUVEC, lung microvascular EC, microvascular dermal EC, Bronchial epithelium, small airway epithelium, NCI-H292, HPAEC, lung fibroblasts, and dermal fibroblasts. The expression of this gene in cells derived from or within the lung suggests that this gene may be involved in normal conditions as well as pathological and inflammatory lung disorders that include chronic obstructive pulmonary disease, asthma, allergy and emphysema.

[0739] Interestingly, expression of this gene is higher in untreated HPAEC (CTs=27-28) as compared to TNF alpha +IL-1 beta treated cells (CTs=30-31). Thus, expression of this gene can be used to distinguish the treated from untreated HPAEC samples.

[0740] In addition, high expression of this gene is also detected in normal tissues represented by colon, lung, thymus and kidney. Interestingly, expression of this gene is much lower in colon samples from patients with IBD colitis and Crohn's disease relative CTs=31-33) to normal colon (CTs=28-29). Therefore, therapeutic modulation of the activity of the protein encoded by this gene may be useful in the treatment of inflammatory bowel disease.

[0741] Panel CNS—1 Summary: Ag693 This panel confirms the expression of the CG92813-01 gene at low levels in the brains of an independent group of individuals. Please see panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.

[0742] Q. NOV19a (CG93088-01: moncarboxylate transporter)

[0743] Expression of gene CG93088-01 was assessed using the primer-probe set Ag3841, described in Table QA. Results of the RTQ-PCR runs are shown in Tables QB, QC, and QD.

TABLE QA
Probe Name Ag3841
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-ttcctatggcattgttgtaggt-3′	22	583	185
Probe	TET-5′-tggtttattatacactgcaacagtgacca-3′-TAMRA	29	613	186
Reverse	5′-atcgtcaaaatactggcacgta-3′	22	643	187

[0744]

TABLE QB
CNS_neurodegeneration_v1.0
	Rel.	Rel.		Rel.	Rel.
	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)
	Ag3841,	Ag3841,		Ag3841,	Ag3841,
Tissue	Run	Run	Tissue	Run	Run
Name	206873281	224339890	Name	206873281	224339890
AD 1 Hippo	59.5	60.7	Control	11.8	9.9
			(Path) 3
			Temporal
			Ctx
AD 2 Hippo	91.4	77.4	Control	26.4	19.1
			(Path) 4
			Temporal
			Ctx
AD 3 Hippo	15.8	13.0	AD 1	35.1	39.0
			Occipital
			Ctx
AD 4 Hippo	15.0	19.3	AD 2	0.0	0.0
			Occipital
			Ctx
			(Missing)
AD 5 Hippo	43.2	52.5	AD 3	16.8	16.0
			Occipital
			Ctx
AD 6 Hippo	92.7	100.0	AD 4	31.9	28.1
			Occipital
			Ctx
Control 2	25.5	32.3	AD 5	23.8	13.4
Hippo			Occipital
			Ctx
Control 4	45.7	54.7	AD 6	15.2	28.1
Hippo			Occipital
			Ctx
Control	16.6	14.8	Control 1	7.0	6.1
(Path) 3			Occipital
Hippo			Ctx
AD 1	55.1	54.3	Control 2	35.4	32.3
Temporal			Occipital
Ctx			Ctx
AD 2	61.6	62.0	Control 3	20.6	18.0
Temporal			Occipital
Ctx			Ctx
AD 3	12.9	16.4	Control 4	16.8	22.7
Temporal			Occipital
Ctx			Ctx
AD 4	42.9	44.1	Control	52.5	50.0
Temporal			(Path) 1
Ctx			Occipital
			Ctx
AD 5 Inf	96.6	92.0	Control	9.2	12.2
Temporal			(Path) 2
Ctx			Occipital
			Ctx
AD 5 Sup	100.0	83.5	Control	5.1	5.3
Temporal			(Path) 3
Ctx			Occipital
			Ctx
AD 6 Inf	51.4	48.3	Control	6.3	6.2
Temporal			(Path) 4
Ctx			Occipital
			Ctx
AD 6 Sup	56.3	49.0	Control 1	14.4	15.9
Temporal			Parietal Ctx
Ctx
Control 1	18.4	15.9	Control 2	63.7	76.3
Temporal			Parietal Ctx
Ctx
Control 2	23.0	27.4	Control 3	14.3	14.9
Temporal			Parietal Ctx
Ctx
Control 3	12.4	17.9	Control	24.0	28.3
Temporal			(Path) 1
Ctx			Parietal Ctx
Control 3	19.9	25.5	Control	25.5	24.8
Temporal			(Path) 2
Ctx			Parietal Ctx
Control	22.2	20.7	Control	8.8	7.9
(Path) 1			(Path) 3
Temporal			Parietal Ctx
Ctx
Control	29.1	26.6	Control	27.7	21.2
(Path) 2			(Path) 4
Temporal			Parietal Ctx
Ctx

[0745]

TABLE QC
General_screening_panel_v1.4
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag3841,		Ag3841,
	Run		Run
Tissue Name	213604526	Tissue Name	213604526
Adipose	1.6	Renal ca. TK-10	5.6
Melanoma*	0.0	Bladder	3.1
Hs688(A).T
Melanoma*	0.1	Gastric ca. (liver met.)	2.6
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma*	0.0	Colon ca. SW-948	0.8
LOXIMVI
Melanoma* SK-	0.4	Colon ca. SW480	1.7
MEL-5
Squamous cell	5.7	Colon ca.* (SW480	2.4
carcinoma SCC-4		met) SW620
Testis Pool	2.3	Colon ca. HT29	0.0
Prostate ca.* (bone	10.2	Colon ca. HCT-116	8.7
met) PC-3
Prostate Pool	2.3	Colon ca. CaCo-2	0.6
Placenta	0.0	Colon cancer tissue	0.2
Uterus Pool	3.8	Colon ca. SW1116	0.3
Ovarian ca.	3.0	Colon ca. Colo-205	0.0
OVCAR-3
Ovarian ca.	1.9	Colon ca. SW-48	0.0
SK-OV-3
Ovarian ca.	1.3	Colon Pool	9.9
OVCAR-4
Ovarian ca.	19.9	Small Intestine Pool	3.8
OVCAR-5
Ovarian ca.	0.4	Stomach Pool	2.9
IGROV-1
Ovarian ca.	1.6	Bone Marrow Pool	2.7
OVCAR-8
Ovary	30.6	Fetal Heart	0.8
Breast ca. MCF-7	2.4	Heart Pool	1.9
Breast ca. MDA-	0.0	Lymph Node Pool	8.8
MB-231
Breast ca. BT 549	3.8	Fetal Skeletal Muscle	1.4
Breast ca. T47D	33.9	Skeletal Muscle Pool	0.7
Breast ca. MDA-N	0.0	Spleen Pool	22.4
Breast Pool	9.7	Thymus Pool	3.1
Trachea	8.2	CNS cancer	0.0
		(glio/astro)
		U87-MG
Lung	5.2	CNS cancer	0.0
		(glio/astro)
		U-118-MG
Fetal Lung	3.0	CNS cancer	3.0
		(neuro; met)
		SK-N-AS
Lung ca. NCI-N417	0.7	CNS cancer	2.5
		(astro) SF-
		539
Lung ca. LX-1	0.3	CNS cancer (astro)	2.6
		SNB-75
Lung ca. NCI-H146	0.5	CNS cancer (glio)	0.5
		SNB-19
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-	0.4
		295
Lung ca. A549	0.1	Brain (Amygdala)	1.0
		Pool
Lung ca. NCI-H526	0.0	Brain (cerebellum)	5.5
Lung ca. NCI-H23	3.8	Brain (fetal)	4.7
Lung ca. NCI-H460	2.0	Brain (Hippocampus)	2.9
		Pool
Lung ca. HOP-62	0.2	Cerebral Cortex	2.1
		Pool
Lung ca. NCI-H522	2.4	Brain	1.8
		(Substantia nigra)
		Pool
Liver	0.1	Brain (Thalamus) Pool	2.6
Fetal Liver	8.0	Brain (whole)	3.1
Liver ca. HepG2	3.1	Spinal Cord Pool	3.8
Kidney Pool	8.7	Adrenal Gland	100.0
Fetal Kidney	12.9	Pituitary gland Pool	2.1
Renal ca. 786-0	0.1	Salivary Gland	1.1
Renal ca. A498	0.5	Thyroid (female)	5.2
Renal ca. ACHN	0.7	Pancreatic ca.	0.2
		CAPAN2
Renal ca. UO-31	1.8	Pancreas Pool	5.2

[0746]

TABLE QD
Panel 4.1D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag3841, Run		Ag3841, Run
Tissue Name	170126778	Tissue Name	170126778
Secondary Th1 act	0.3	HUVEC IL-1beta	0.2
Secondary Th2 act	0.3	HUVEC IFN gamma	1.3
Secondary Tr1 act	0.3	HUVEC	0.1
		TNF alpha + IFN gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.3
Secondary Th2 rest	0.1	HUVEC IL-11	1.0
Secondary Tr1 rest	0.0	Lung Microvascular EC	2.3
		none
Primary Th1 act	2.4	Lung Microvascular EC	1.4
		TNF alpha + IL-1beta
Primary Th2 act	1.0	Microvascular Dermal EC	0.6
		none
Primary Tr1 act	1.0	Microsvasular Dermal EC	0.1
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	4.9
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	2.9
		none
Primary Tr1 rest	0.1	Small airway epithelium	3.1
		TNF alpha + IL-1beta
CD45RA CD4	0.2	Coronery artery SMC rest	3.7
lymphocyte act
CD45RO CD4	0.3	Coronery artery SMC	2.3
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.2	Astrocytes rest	4.4
Secondary CD8	0.1	Astrocytes	2.9
lymphocyte rest		TNF alpha + IL-1beta
Secondary CD8	0.1	KU-812 (Basophil) rest	18.6
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	16.4
		PMA/ionomycin
2ry Th1/Th2/Tr1 anti-	0.0	CCD1106 (Keratinocytes)	3.5
CD95 CH11		none
LAK cells rest	0.1	CCD1106 (Keratinocytes)	2.5
		TNF alpha + IL-1beta
LAK cells IL-2	0.1	Liver cirrhosis	0.1
LAK cells IL-2 + IL-12	0.3	NCI-H292 none	0.0
LAK cells IL-2 + IFN	0.2	NCI-H292 IL-4	0.2
gamma
LAK cells IL-2 + IL-18	0.5	NCI-H292 IL-9	0.2
LAK cells	0.0	NCI-H292 IL-13	0.1
PMA/ionomycin
NK Cells IL-2 rest	0.1	NCI-H292 IFN gamma	0.4
Two Way MLR 3 day	0.0	HPAEC none	0.1
Two Way MLR 5 day	0.0	HPAEC	1.5
		TNF alpha + IL-1beta
Two Way MLR 7 day	0.0	Lung fibroblast none	0.1
PBMC rest	0.0	Lung fibroblast	0.0
		TNF alpha + IL-1beta
PBMC PWM	0.7	Lung fibroblast IL-4	0.0
PBMC PHA-L	0.1	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.0
Ramos (B cell)	0.0	Lung fibroblast IFN	0.0
ionomycin		gamma
B lymphocytes PWM	0.9	Dermal fibroblast	0.0
		CCD1070 rest
B lymphocytes CD40L	0.2	Dermal fibroblast	0.0
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 IFN	0.0
PMA/ionomycin		gamma
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.1	Dermal Fibroblasts rest	0.0
Dendritic cells anti-	0.2	Neutrophils TNFa + LPS	0.0
CD40
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	0.3
Macrophages rest	0.1	Lung	0.2
Macrophages LPS	0.0	Thymus	0.3
HUVEC none	0.0	Kidney	100.0
HUVEC starved	0.0

[0747] CNS_neurodegeneration_v1.0 Summary: Ag3841 Two experiments with same probe and primer sets are in excellent agreements. It confirms the expression of the CG93088-01 gene at low levels in the brain in an independent group of individuals. This gene is upregulated in the temporal cortex of Alzheimer's disease patients when compared with non-demented controls (p=0.02 when analyzed by Ancova, estimate of total cDNA loaded per well used as a covariate). This gene may therefore be a small molecule target, and blockade of this transporter may slow or stop the progression of Alzheimer's disease.

[0748] General_screening_panel_v1.4 Summary: Ag3841 Highest expression of the CG93088-01 gene is detected in adrenal gland (CT=25). In addition, this gene is also expressed at high to moderate levels in other tissues with metabolic or endocrine function, such as pancreas, adipose, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. The CG93088-01 gene codes for monocarboxylate transporter, a transporter belonging to sugar transporter family. Recently, a protein belonging to this family was shown to be associated with non-insulin-dependent diabetes mellitus (NIDDM) (Ref. 1). 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 including NIDDM.

[0749] Interestingly, this gene is expressed at much higher levels in fetal (CT=28.7) when compared to adult liver (CT=35.6). This observation suggests that expression of this gene can be used to distinguish fetal from adult liver.

[0750] In addition, this gene is expressed at high to 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.

[0751] See, generally,

[0752] McVie-Wylie A J, Lamson D R, Chen Y T. (2001) Molecular cloning of a novel member of the GLUT family of transporters, SLC2a10 (GLUT10), localized on chromosome 20q13.1: a candidate gene for NIDDM susceptibility. Genomics 72(1):113-7. PMID: 11247674

[0753] Panel 2.2 Summary: Ag3841 Results from one experiment with the CG93088-01 gene are not included. The amp plot indicates that there were experimental difficulties with this run.

[0754] Panel 4.1D Summary: Ag3841 Highest expression of the CG93088-01 gene is detected in kidney sample (CT=26). 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.

[0755] In addition, low to moderate expression of this gene is also seen in TNF alpha+IL-1 beta treated HPAEC, keratinocytes, basophils, astrocytes, coronery artery SMC, small airway epithelium, lung microvascular EC, microvascular dermal EC and PWM treated B lymphocytes. Interestingly, expression of this gene is stimulated in TNF alpha+IL-1 beta treated HPAEC, IFN gamma/IL-11 treated HUVEC cells, PWM treated PBMC cells, IL-2+IL-18 treated LAK cells, activated primary and secondary Th1, Th2, Tr1 cells as compared to their corresponding untreated or resting cells. 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.

[0756] R. NOV21a (CG93345-01: GPCR)

[0757] Expression of gene CG93345-01 was assessed using the primer-probe set Ag3850, described in Table RA. Results of the RTQ-PCR runs are shown in Tables RB.

TABLE RA
Probe Name Ag3850
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-taatcctgcaggcagtattgag-3′	22	737	188
Probe	TET-5′-attgcttcccaggaagacaggctcaa-3′-TAMRA	26	760	189
Reverse	5′-tgagagagacacaggtgttgag-3′	22	790	190

[0758]

TABLE RB
General_screening_panel_v1.4
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag3850,		Ag3850,
	Run		Run
Tissue Name	218998898	Tissue Name	218998898
Adipose	0.0	Renal ca. TK-10	0.0
Melanoma*	0.0	Bladder	0.6
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma*	0.0	Colon ca. SW-948	0.0
LOXIMVI
Melanoma*	0.0	Colon ca. SW480	0.0
SK-MEL-5
Squamous cell	0.0	Colon ca.* (SW480	0.4
carcinoma SCC-4		met) SW620
Testis Pool	1.8	Colon ca. HT29	0.0
Prostate ca.* (bone	0.0	Colon ca. HCT-116	0.0
met) PC-3
Prostate Pool	1.7	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.	0.0	Colon ca. Colo-205	0.0
OVCAR-3
Ovarian ca.	0.6	Colon ca. SW-48	0.0
SK-OV-3
Ovarian ca.	0.0	Colon Pool	0.0
OVCAR-4
Ovarian ca.	0.0	Small Intestine Pool	0.3
OVCAR-5
Ovarian ca.	0.0	Stomach Pool	0.0
IGROV-1
Ovarian ca.	0.0	Bone Marrow Pool	0.0
OVCAR-8
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 Muscle	0.4
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	0.0
Breast Pool	0.2	Thymus Pool	0.0
Trachea	0.0	CNS cancer	0.0
		(glio/astro)
		U87-MG
Lung	0.0	CNS cancer	0.0
		(glio/astro)
		U-118-MG
Fetal Lung	0.0	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 (astro)	0.0
		SNB-75
Lung ca. NCI-H146	4.7	CNS cancer (glio)	0.0
		SNB-19
Lung ca. SHP-77	100.0	CNS cancer (glio) SF-	0.5
		295
Lung ca. A549	0.0	Brain (Amygdala)	0.0
		Pool
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.0
Lung ca. NCI-H23	0.0	Brain (fetal)	0.3
Lung ca. NCI-H460	0.0	Brain (Hippocampus)	0.0
		Pool
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain	0.0
		(Substantia nigra)
		Pool
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	0.0	Spinal Cord Pool	0.0
Kidney Pool	1.1	Adrenal Gland	0.0
Fetal Kidney	3.1	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	0.0	Pancreatic ca.	0.0
		CAPAN2
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[0759] CNS_neurodegeneration_v1.0 Summary: Ag3850 Expression of the CG93345-01 gene is low/undetectable in all samples on this panel (CTs>35).

[0760] General_screening_panel_v1.4 Summary: Ag3850 Expression of the CG93345-01 gene is restricted to a sample derived from a lung cancer cell line (CT=31.1). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of lungcancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of lung cancer.

[0761] Panel 4.1D Summary: Ag3850 Expression of the CG93345-01 gene is low/undetectable in all samples on this panel (CTs>35).

[0762] S. NOV22a (CG93400-01: GPCR)

[0763] Expression of gene CG93400-01 was assessed using the primer-probe set Ag3853, described in Table SA. Results of the RTQ-PCR runs are shown in Tables SB, and SC.

TABLE SA
Probe Name Ag3853
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-acgatgctgagaatcttcttgt-3′	22	274	191
Probe	TET-5′-tacatgcattgcccaggaattcttca-3′-TAMRA	26	321	192
Reverse	5′-aagactccatgtctgtgaatcc-3′	22	352	193

[0764]

TABLE SB
General_screening_panel_v1.4
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag3853,		Ag3853,
	Run		Run
Tissue Name	218998963	Tissue Name	218998963
Adipose	0.0	Renal ca. TK-10	0.0
Melanoma*	0.0	Bladder	0.8
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma*	0.0	Colon ca. SW-948	0.4
LOXIMVI
Melanoma* SK-	0.0	Colon ca. SW480	0.0
MEL-5
Squamous cell	0.4	Colon ca.* (SW480	0.0
carcinoma SCC-4		met) SW620
Testis Pool	1.0	Colon ca. HT29	0.0
Prostate ca.* (bone	0.0	Colon ca. HCT-116	0.0
met) PC-3
Prostate Pool	1.8	Colon ca. CaCo-2	0.0
Placenta	0.0	Colon cancer tissue	0.6
Uterus Pool	0.0	Colon ca. SW1116	0.0
Ovarian ca.	0.0	Colon ca. Colo-205	0.0
OVCAR-3
Ovarian ca.	0.0	Colon ca. SW-48	0.0
SK-OV-3
Ovarian ca.	0.0	Colon Pool	0.0
OVCAR-4
Ovarian ca.	0.0	Small Intestine Pool	0.0
OVCAR-5
Ovarian ca.	0.0	Stomach Pool	0.0
IGROV-1
Ovarian ca.	0.0	Bone Marrow Pool	0.0
OVCAR-8
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-	0.0	Lymph Node Pool	0.4
MB-231
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.6
Breast ca. MDA-N	0.0	Spleen Pool	0.0
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
		(glio/astro)
		U-118-MG
Fetal Lung	0.0	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 (astro)	0.0
		SNB-75
Lung ca. NCI-H146	2.8	CNS cancer (glio)	0.0
		SNB-19
Lung ca. SHP-77	100.0	CNS cancer (glio) SF-	0.0
		295
Lung ca. A549	0.0	Brain	0.0
		(Amygdala) Pool
Lung ca. NCI-H526	0.8	Brain (cerebellum)	0.0
Lung ca. NCI-H23	0.0	Brain (fetal)	0.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus)	0.0
		Pool
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain	0.0
		(Substantia nigra)
		Pool
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	0.0	Spinal Cord Pool	0.0
Kidney Pool	0.3	Adrenal Gland	0.0
Fetal Kidney	3.1	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	0.0	Pancreatic ca.	0.0
		CAPAN2
Renal ca. UO-31	0.0	Pancreas Pool	0.4

[0765]

TABLE SC
Panel 4.1D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag3853, Run		Ag3853, Run
Tissue Name	170121471	Tissue Name	170121471
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	0.0
		TNF alpha + IFN gamma
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	0.0
		none
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	0.0
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	0.0
		none
Primary Tr1 rest	0.0	Small airway epithelium	0.0
		TNF alpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	0.0
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes	0.0
lymphocyte rest		TNF alpha + IL-1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	1.5
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNF alpha + 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	0.0	NCI-H292 IL-4	0.0
gamma
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells	0.0	NCI-H292 IL-13	0.0
PMA/ionomycin
NK Cells IL-2 rest	100.0	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	0.0
		TNF alpha + IL-1beta
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
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)	0.0	Lung fibroblast IFN	0.0
ionomycin		gamma
B lymphocytes PWM	0.0	Dermal fibroblast	0.0
		CCD1070 rest
B lymphocytes CD40L	0.0	Dermal fibroblast	0.0
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 IFN	0.0
PMA/ionomycin		gamma
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.0
Dendritic cells anti-	0.0	Neutrophils TNFa + LPS	0.0
CD40
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	0.0
Macrophages rest	0.0	Lung	0.0
Macrophages LPS	0.0	Thymus	0.0
HUVEC none	0.0	Kidney	0.0
HUVEC starved	0.0

[0766] CNS_neurodegeneration_v1.0 Summary: Ag3853 Expression of the CG93400-01 gene is low/undetectable in all samples on this panel (CTs>35).

[0767] General_screening_panel_v1.4 Summary: Ag3853 Expression of the CG93400-01 gene is restricted to a sample derived from a lung cancer cell line (CT=31). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of lung cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of lung cancer.

[0768] Panel 4.1D Summary: Ag3853 Expression of the CG93400-01 gene is restricted to a sample derived from IL-2 treated NK cells (CT=31.5). Thus, expression of this gene may be used to differentiate between this sample and other samples on this panel and as a marker of activated NK cells.

[0769] T. NOV23a (CG93410-01: GLUTAMATE RECEPTOR 5)

[0770] Expression of gene CG93410-01 was assessed using the primer-probe set Ag1682, described in Table TA. Results of the RTQ-PCR runs are shown in Tables TB and TC.

TABLE TA
Probe Name Ag1682
				SEQ
			Start	ID
Primers	Sequences	Length	Position	No:
Forward	5′-CATTGAGTATGTGACGCAGAG	22	471	194
	A-3′
Probe	TET-5′-aactgcaacctcactca	25	446	195
	gatcgggg-3′-TAMRA
Reverse	5′-taggtgttcccactccgtaac	21	407	196
	-3′

[0771]

TABLE TB
Panel 1.3D
	Rel.	Rel.		Rel.	Rel.
	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)
	Ag1682,	Ag1682,		Ag1682,	Ag1682,
	Run	Run		Run	Run
Tissue Name	146581572	148168380	Tissue Name	146581572	148168380
Liver	0.8	0.6	Kidney (fetal)	0.7	0.3
adenocarcinoma
Pancreas	0.2	0.0	Renal ca. 786-0	0.2	0.5
Pancreatic ca.	0.8	0.8	Renal ca.	1.8	1.6
CAPAN 2			A498
Adrenal gland	1.7	2.5	Renal ca. RXF	0.4	0.4
			393
Thyroid	0.2	0.3	Renal ca.	0.1	0.2
			ACHN
Salivary gland	1.4	0.4	Renal ca. UO-	0.0	0.0
			31
Pituitary gland	0.1	0.4	Renal ca. TK-	0.1	0.4
			10
Brain (fetal)	5.7	4.5	Liver	0.0	0.1
Brain (whole)	15.1	18.3	Liver (fetal)	0.5	0.8
Brain (amygdala)	13.6	12.1	Liver ca.	0.4	0.9
			(hepatoblast)
			HepG2
Brain	3.5	3.9	Lung	0.8	0.0
(cerebellum)
Brain	20.4	17.7	Lung (fetal)	1.0	1.0
(hippocampus)
Brain (substantia	3.7	4.5	Lung ca.	1.0	0.5
nigra)			(small cell)
			LX-1
Brain (thalamus)	19.2	17.6	Lung ca.	2.8	2.2
			(small cell)
			NCI-H69
Cerebral Cortex	30.1	31.4	Lung ca.	100.0	100.0
			(s.cell var.)
			SHP-77
Spinal cord	2.2	1.4	Lung ca.	1.1	1.0
			(large
			cell) NCI-
			H460
glio/astro	3.8	1.6	Lung ca. (non-	0.3	0.6
U87-MG			sm. cell) A549
glio/astro U-118-	4.0	3.3	Lung ca. (non-	1.1	1.0
MG			s.cell) NCI-
			H23
astrocytoma	0.1	0.0	Lung ca. (non-	1.4	1.1
SW1783			s.cell) HOP-62
neuro*; met	2.0	1.1	Lung ca. (non-	0.0	0.0
SK-N-AS			s.cl) NCI-
			H522
astrocytoma SF-	0.7	0.9	Lung ca.	0.2	0.0
539			(squam.) SW
			900
astrocytoma	3.4	3.7	Lung ca.	0.3	0.3
SNB-75			(squam.) NCI-
			H596
glioma SNB-19	0.3	0.8	Mammary	6.1	2.8
			gland
glioma U251	0.2	0.2	Breast ca.*	0.7	0.4
			(pl.ef) MCF-7
glioma SF-295	0.2	0.0	Breast ca.*	1.7	1.1
			(pl.ef) MDA-
			MB-231
Heart (fetal)	1.3	2.1	Breast ca.*	10.6	9.3
			(pl.ef) T47D
Heart	0.5	0.0	Breast ca. BT-	3.1	2.4
			549
Skeletal muscle	7.2	8.0	Breast ca.	0.5	0.6
(fetal)			MDA-N
Skeletal muscle	0.1	0.0	Ovary	0.4	0.8
Bone marrow	0.7	0.5	Ovarian ca.	0.2	0.5
			OVCAR-3
Thymus	0.3	0.7	Ovarian ca.	0.0	0.0
			OVCAR-4
Spleen	0.7	0.8	Ovarian ca.	1.8	1.0
			OVCAR-5
Lymph node	0.6	1.2	Ovarian ca.	0.3	0.2
			OVCAR-8
Colorectal	0.4	0.5	Ovarian ca.	0.1	0.0
			IGROV-1
Stomach	1.6	1.4	Ovarian ca.*	0.6	0.8
			(ascites) SK-
			OV-3
Small intestine	2.8	2.4	Uterus	0.7	0.3
Colon ca. SW480	0.0	0.1	Placenta	3.2	2.2
Colon ca.*	0.4	0.1	Prostate	0.8	0.8
SW620(SW480
met)
Colon ca. HT29	0.0	0.2	Prostate ca.*	0.1	0.9
			(bone met)PC-3
Colon ca. HCT-	0.0	0.2	Testis	5.6	3.9
116
Colon ca. CaCo-2	0.7	0.0	Melanoma	0.8	0.3
			Hs688(A).T
Colon ca.	0.9	0.6	Melanoma*	0.5	0.9
tissue(ODO3866)			(met)
			Hs688(B).T
Colon ca. HCC-	0.4	0.7	Melanoma	0.3	0.0
2998			UACC-62
Gastric ca.* (liver	0.8	0.7	Melanoma	0.4	0.2
met) NCI-N87			M14
Bladder	1 .3	0.8	Melanoma	0.3	0.2
			LOX IMVI
Trachea	1.3	0.7	Melanoma*	0.2	0.1
			(met) SK-
			MEL-5
Kidney	0.0	0.3	Adipose	0.6	0.2

[0772]

TABLE TC
Panel 2D
	Rel.	Rel.		Rel.	Rel.
	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)
	Ag1682,	Ag1682,		Ag1682,	Ag1682,
	Run	Run		Run	Run
Tissue Name	148168595	148399984	Tissue Name	148168595	148399984
Normal Colon	21.2	39.2	Kidney	0.0	2.6
			Margin
			8120608
CC Well to Mod	2.0	2.9	Kidney	1.4	1.7
Diff (ODO3866)			Cancer
			8120613
CC Margin	2.5	2.0	Kidney	0.0	7.4
(ODO3866)			Margin
			8120614
CC Gr.2	10.3	15.2	Kidney	8.2	20.3
rectosigmoid			Cancer
(ODO3868)			9010320
CC Margin	2.3	0.9	Kidney	5.9	9.9
(ODO3868)			Margin
			9010321
CC Mod Diff	12.6	11.7	Normal Uterus	3.2	2.2
(ODO3920)
CC Margin	4.3	8.8	Uterus Cancer	8.0	14.9
(ODO3920)			064011
CC Gr.2 ascend	11.7	17.8	Normal	4.3	9.8
colon			Thyroid
(ODO3921)
CC Margin	1.9	3.4	Thyroid	3.2	3.0
(ODO3921)			Cancer
			064010
CC from Partial	4.6	15.6	Thyroid	7.2	5.2
Hepatectomy			Cancer
(ODO4309)			A302152
Mets
Liver Margin	2.3	6.9	Thyroid	3.3	8.7
(ODO4309)			Margin
			A302153
Colon mets to	5.7	5.4	Normal Breast	26.6	39.5
lung (OD04451-
01)
Lung Margin	3.9	10.2	Breast Cancer	2.0	4.5
(OD04451-02)			(OD04566)
Normal Prostate	8.3	18.9	Breast Cancer	7.3	10.5
6546-1			(OD04590-01)
Prostate Cancer	27.7	52.9	Breast Cancer	6.9	20.7
(OD04410)			Mets
			(OD04590-03)
Prostate Margin	47.6	84.7	Breast Cancer	9.7	18.7
(OD04410)			Metastasis
			(OD04655-05)
Prostate Cancer	14.8	35.8	Breast Cancer	21.9	26.8
(OD04720-01)			064006
Prostate Margin	24.7	50.0	Breast Cancer	7.1	15.8
(OD04720-02)			1024
Normal Lung	25.3	50.7	Breast Cancer	4.5	8.5
061010			9100266
Lung Met to	1.6	4.9	Breast Margin	9.4	16.5
Muscle			9100265
(ODO4286)
Muscle Margin	7.3	10.5	Breast Cancer	12.2	12.0
(ODO4286)			A209073
Lung Malignant	100.0	100.0	Breast Margin	14.6	30.4
Cancer			A209073
(OD03126)
Lung Margin	21.6	49.7	Normal Liver	3.2	2.8
(OD03126)
Lung Cancer	10.6	13.6	Liver Cancer	11.9	28.3
(OD04404)			064003
Lung Margin	9.3	9.7	Liver Cancer	4.7	5.9
(OD04404)			1025
Lung Cancer	11.5	11.7	Liver Cancer	2.6	0.7
(OD04565)			1026
Lung Margin	6.1	11.7	Liver Cancer	7.7	11.3
(OD04565)			6004-T
Lung Cancer	12.6	27.2	Liver Tissue	8.7	25.0
(OD04237-01)			6004-N
Lung Margin	11.0	24.0	Liver Cancer	0.9	3.0
(OD04237-02)			6005-T
Ocular Mel Met	0.4	3.4	Liver Tissue	0.8	1.0
to Liver			6005-N
(ODO4310)
Liver Margin	2.5	3.2	Normal	34.2	76.8
(ODO4310)			Bladder
Melanoma Mets	8.0	8.4	Bladder	4.2	4.2
to Lung			Cancer 1023
(OD04321)
Lung Margin	12.2	10.9	Bladder	6.0	15.0
(OD04321)			Cancer
			A302173
Normal Kidney	24.3	42.9	Bladder	15.6	27.7
			Cancer
			(OD04718-01)
Kidney Ca,	27.0	15.9	Bladder	7.8	20.9
Nuclear grade 2			Normal
(OD04338)			Adjacent
			(OD04718-03)
Kidney Margin	7.3	25.7	Normal Ovary	0.9	5.1
(OD04338)
Kidney Ca	23.7	42.0	Ovarian	13.8	34.2
Nuclear grade			Cancer
1/2 (OD04339)			064008
Kidney Margin	17.3	29.1	Ovarian	5.9	16.3
(OD04339)			Cancer
			(OD04768-07)
Kidney Ca,	20.6	25.9	Ovary Margin	3.6	9.1
Clear cell type			(OD04768-08)
(OD04340)
Kidney Margin	18.6	27.0	Normal	14.0	17.7
(OD04340)			Stomach
Kidney Ca,	3.9	10.6	Gastric Cancer	0.4	1.0
Nuclear grade 3			9060358
(OD04348)
Kidney Margin	16.3	31.6	Stomach	6.7	13.3
(OD04348)			Margin
			9060359
Kidney Cancer	5.0	10.4	Gastric Cancer	1.5	6.8
(OD04622-01)			9060395
Kidney Margin	0.9	0.9	Stomach	6.2	9.7
(OD04622-03)			Margin
			9060394
Kidney Cancer	4.7	8.0	Gastric Cancer	6.5	16.0
(OD04450-01)			9060397
Kidney Margin	4.5	9.9	Stomach	1.5	4.0
(OD04450-03)			Margin
			9060396
Kidney Cancer	0.7	0.9	Gastric Cancer	8.4	30.1
8120607			064005

[0773] Panel 1.3D Summary: Ag1682 Two experiments with same probe and primer set are in excellent agreement with highest expression of this gene in lung cancer SHP-77 cell line (CTs=26). In addition, low to moderate expression of this gene is also observed in number of cancer cell lines (melanoma, ovarian, breast, lung, renal, colon, CNS and liver adenocarcinoma). 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 cancers.

[0774] In addition, this gene is expressed at high to 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. CG93410-01 codes for a splice variant of glutamate receptor 5 (GluR5). Mutation or allelic variation in GluR5 has been shown to be associated with familial amyotrophic lateral sclerosis (ALS) (Ref. 1) and Juvenile absence epilepsy (JAE)(Ref.2). Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of ALS and JAE.

[0775] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adrenal gland, fetal skeletal muscle, fetal heart, fetal 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.

[0776] Interestingly, this gene is expressed at much higher levels in fetal (CT=30-33) when compared to adult skeletal muscle, heart and liver (CT>35). This observation suggests that expression of this gene can be used to distinguish these fetal from adult tissue.

[0777] See, generally,

[0778] Eubanks J H, Puranam R S, Kleckner N W, Bettler B, Heinemann S F, McNamara J O. (1993) The gene encoding the glutamate receptor subunit GluR5 is located on human chromosome 21q21.11-22.1 in the vicinity of the gene for familial amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 90(1):178-82. PMID: 8419920

[0779] Sander T, Hildmann T, Kretz R, Furst R, Sailer U, Bauer G, Schmitz B, Beck-Mannagetta G, Wienker T F, Janz D. (1997). PMID: 9259378

[0780] Panel 2D Summary: Ag1682 Two experiments with same probe and primer set are in excellent agreement with highest expression of this gene in lung malignant cancer (OD03126) (CTs=28-31). In addition, expression of this gene is seen in both normal, control margin and cancer tissue. Please see Panel 1.4 for a discussion of the potential utility of this gene.

[0781] U. NOV24a (CG93722-01: SERINE PROTEASE HEPSIN)

[0782] Expression of gene CG93722-01 was assessed using the primer-probe sets Ag1299, Ag897, Ag898 and Ag228, described in Tables UA, UB, UC and UD. Results of the RTQ-PCR runs are shown in Tables UE, and UF.

TABLE UA
Probe Name Ag1299
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-gcctatttgcctaccttttgat-3′	22	766	197
Probe	TET-5′-ccaaatcctggacggaaacacaaagt-3′-TAMRA	26	793	198
Reverse	5′-cttccccagccacttataaaac-3′	22	819	199

[0783]

TABLE UB
Probe Name Ag897
			Start	SEQ ID
Primers	Sequences	Length	Position	No:
Forward	5′-gcctatttgcctaccttttga-3′	21	766	200
Probe	TET-5′-ccaaatcctggacggaaacacaaagt-3′-TAMRA	26	793	201
Reverse	5′-gttcttccccagccacttat-3′	20	824	202

[0784]

TABLE UC
Probe Name Ag898
			Start	SEQ ID
Primers	Sequences	Length	Positions	No:
Forward	5′-gcctatttgcctaccttttga-3′	21	766	203
Probe	TET-5′-ccaaatcctggacggaaacacaaagt-3′-TAMRA	26	793	204
Reverse	5′-gttcttccccagccacttat-3′	20	824	205

[0785]

TABLE UD
Probe Name Ag228
			Start	SEQ ID
Primers	Sequences	Length	Positions	No:
Forward	5′-tgtggaacagcaccgcttaag-3′	21	365	206
Probe	TET-5′-ccctataatccgagacccttgcaacaca-3′-TAMRA	28	388	207
Reverse	5′-atgcgccagcttgtgctt-3′	18	423	208

[0786]

TABLE UE
Panel 1
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag228,		Ag228,
	Run		Run
Tissue Name	87590239	Tissue Name	87590239
Endothelial cells	0.0	Renal Ca. 786-0	0.0
Endothelial cells	0.0	Renal ca. A498	0.0
(treated)
Pancreas	0.0	Renal ca. RXF 393	0.0
Pancreatic ca. CAPAN 2	0.0	Renal ca. ACHN	0.0
Adrenal gland	0.0	Renal ca. UO-31	0.0
Thyroid	0.0	Renal ca. TK-10	0.0
Salivary gland	0.0	Liver	0.0
Pituitary gland	0.0	Liver (fetal)	0.0
Brain (fetal)	0.0	Liver ca.	0.0
		(hepatoblast) HepG2
Brain (whole)	0.0	Lung	0.0
Brain (amygdala)	0.0	Lung (fetal)	0.0
Brain (cerebellum)	0.0	Lung ca. (small cell)	0.0
		LX-1
Brain (hippocampus)	0.0	Lung ca. (small cell)	0.0
		NCI-H69
Brain (substantia nigra)	0.0	Lung ca. (s.cell var.)	0.0
		SHP-77
Brain (thalamus)	0.0	Lung ca. (large	0.0
		cell) NCI-H460
Brain (hypothalamus)	0.0	Lung ca. (non-sm.	0.0
		cell) A549
Spinal cord	0.0	Lung ca. (non-s.cell)	0.0
		NCI-H23
glio/astro U87-MG	0.0	Lung ca. (non-s.cell)	0.0
		HOP-62
glio/astro U-118-MG	0.0	Lung ca. (non-s.cl)	0.0
		NCI-H522
astrocytoma SW1783	0.0	Lung ca. (squam.)	0.0
		SW 900
neuro*; met SK-N-AS	0.0	Lung ca. (squam.)	0.0
		NCI-H596
astrocytoma SF-539	0.0	Mammary gland	0.0
astrocytoma SNB-75	0.0	Breast ca.* (pl.ef)	0.0
		MCF-7
glioma SNB-19	0.0	Breast ca.* (pl.ef)	0.0
		MDA-MB-231
glioma U251	0.0	Breast ca.* (pl. ef)	0.0
		T47D
glioma SF-295	0.0	Breast ca. BT-549	0.0
Heart	0.0	Breast ca. MDA-N	0.0
Skeletal muscle	0.0	Ovary	0.0
Bone marrow	0.0	Ovarian ca. OVCAR-3	0.0
Thymus	0.0	Ovarian ca. OVCAR-4	0.0
Spleen	0.0	Ovarian ca. OVCAR-5	0.0
Lymph node	0.0	Ovarian ca. OVCAR-8	0.0
Colon (ascending)	0.0	Ovarian ca. IGROV-1	0.0
Stomach	0.0	Ovarian ca. (ascites)	0.0
		SK-OV-3
Small intestine	0.0	Uterus	0.0
Colon ca. SW480	0.0	Placenta	0.0
Colon ca.* SW620	0.0	Prostate	0.0
(SW480 met)
Colon ca. HT29	0.0	Prostate ca.* (bone	0.0
		met) PC-3
Colon ca. HCT-116	0.0	Testis	100.0
Colon ca. CaCo-2	0.0	Melanoma	0.0
		Hs688(A).T
Colon ca. HCT-15	0.0	Melanoma* (met)	0.0
		Hs688(B).T
Colon ca. HCC-2998	0.0	Melanoma UACC-62	0.0
Gastric ca. * (liver met)	0.0	Melanoma M14	0.0
NCI-N87
Bladder	0.0	Melanoma LOX	0.0
		IMVI
Trachea	0.0	Melanoma* (met)	0.0
		SK-MEL-5
Kidney	0.0	Melanoma SK-MEL-	0.0
		28
Kidney (fetal)	0.0

[0787]

TABLE UF
Panel 1.3D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag898,		Ag898,
	Run		Run
Tissue Name	153559338	Tissue Name	153559338
Liver adenocarcinoma	0.2	Kidney (fetal)	0.1
Pancreas	0.3	Renal ca. 786-0	0.0
Pancreatic ca.	0.0	Renal ca. A498	0.0
CAPAN 2
Adrenal gland	0.2	Renal ca. RXF 393	0.0
Thyroid	0.4	Renal ca. ACHN	0.0
Salivary gland	0.0	Renal ca. UO-31	0.0
Pituitary gland	0.2	Renal ca. TK-10	0.2
Brain (fetal)	0.2	Liver	0.0
Brain (whole)	0.2	Liver (fetal)	0.3
Brain (amygdala)	0.5	Liver ca.	0.0
		(hepatoblast) HepG2
Brain (cerebellum)	0.1	Lung	0.0
Brain (hippocampus)	0.0	Lung (fetal)	0.5
Brain	0.0	Lung ca. (small cell)	0.0
(substantia nigra)		LX-1
Brain (thalamus)	0.2	Lung ca. (small cell)	0.0
		NCI-H69
Cerebral Cortex	0.0	Lung ca.	0.0
		(s.cell var.)
		SHP-77
Spinal cord	0.0	Lung ca. (large	0.3
		cell) NCI-H460
glio/astro U87-MG	0.0	Lung ca. (non-sm.	0.0
		cell) A549
glio/astro U-118-MG	0.0	Lung ca.	0.2
		(non-s.cell)
		NCI-H23
astrocytoma SW1783	0.2	Lung ca.	0.0
		(non-s.cell)
		HOP-62
neuro*; met SK-N-AS	0.0	Lung ca. (non-s.cl)	0.0
		NCI-H522
astrocytoma SF-539	0.2	Lung ca. (Squam.)	0.0
		SW 900
astrocytoma SNB-75	0.2	Lung ca. (Squam.)	0.0
		NCI-H596
glioma SNB-19	0.0	Mammary gland	0.0
glioma U251	0.0	Breast ca.* (pl.ef)	0.0
		MCF-7
glioma SF-295	0.2	Breast ca.* (pl.ef)	0.0
		MDA-MB-231
Heart (fetal)	0.2	Breast ca.* (pl.ef)	0.2
		T47D
Heart	0.0	Breast ca. BT-549	0.1
Skeletal muscle (fetal)	1.0	Breast ca. MDA-N	0.0
Skeletal muscle	0.2	Ovary	0.3
Bone marrow	0.0	Ovarian ca.	0.0
		OVCAR-3
Thymus	0.0	Ovarian ca.	0.0
		OVCAR-4
Spleen	0.0	Ovarian ca.	0.0
		OVCAR-5
Lymph node	0.0	Ovarian ca.	0.0
		OVCAR-8
Colorectal	0.0	Ovarian ca.	0.0
		IGROV-1
Stomach	0.2	Ovarian ca.*	0.1
		(ascites)
		SK-OV-3
Small intestine	0.0	Uterus	0.2
Colon ca. SW480	0.0	Placenta	0.6
Colon ca.*	0.0	Prostate	0.5
SW620(SW480 met)
Colon ca. HT29	0.0	Prostate ca.* (bone	0.2
		met)PC-3
Colon ca. HCT-116	0.0	Testis	100.0
Colon ca. CaCo-2	0.0	Melanoma	0.0
		Hs688(A).T
Colon ca.	0.0	Melanoma* (met)	0.0
tissue(ODO3866)		Hs688(B).T
Colon ca. HCC-2998	0.2	Melanoma	0.0
		UACC-62
Gastric ca.* (liver met)	0.0	Melanoma M14	0.0
NCI-N87
Bladder	0.0	Melanoma LOX	0.0
		IMVI
Trachea	0.0	Melanoma* (met)	0.0
		SK-MEL-5
Kidney	0.0	Adipose	0.0

[0788] Panel 1 Summary: Ag228 Expression of the CG93722-01 gene is detected exclusively in testis. Thus, expression of this gene can be used to distinguish testis from other samples used in this panel. Therefore, therapeutic modulation of the activity of the serine protease encoded by this gene may be useful in the treatment of fertility and hypogonadism.

[0789] Panel 1.3D Summary: Ag898 Expression of the CG93722-01 gene is detected exclusively in testis. Thus, expression of this gene can be used to distinguish testis from other samples used in this panel. Therefore, therapeutic modulation of the activity of the serine protease encoded by this gene may be useful in the treatment of fertility and hypogonadism.

[0790] Panel 4D Summary: Ag1299 Expression of the CG93722-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0791] V. NOV25a, NOV25b, and NOV25c (CG93858-01 and CG93858-02 and CG56914-03: Fibulin 6 like)

[0792] Expression of gene CG93858-01 and varinats CG93858-02 and CG56914-03 was assessed using the primer-probe sets Ag1315b, Ag1316b, Ag1924, Ag900, Ag3960, and Ag4338. In addition expression of gene CG93858-02 was also assessed using the primer-probe sets Ag343, Ag3108, Ag771, Ag772, Ag3899 with CG56914-03 corresponding to Ag3108 and Ag3899 only. The probes are described in Tables VA, VB, VC, VD, VE, VF, VG, VH, VI, VJ and VK. Results of the RTQ-PCR runs are shown in Tables VL, VM, VN, VO, VP, VQ, and VR.

TABLE VA
Probe Name Ag1315b
			Start	SEQ ID
Primers	Sequences	Length	Positions	No:
Forward	5′-catcagaggttcttcgaaagc-3′	21	6744	209
Probe	TET-5′-cacaacggaccaoacagcgataagat-3′-TAMRA	26	6712	210
Reverse	5′-aggactgtgacaatacgattgg-3′	22	6690	211

[0793]

TABLE VB
Probe Name Ag1316b
			Start	SEQ ID
Primers	Sequences	Length	Positions	No:
Forward	5′-aatgccatggggacttactact-3′	22	6572	212
Probe	TET-5′-cctaaaggcctcaccatagctgcaga-3′-TAMRA	26	6602	213
Reverse	5′-cccaaagcacactcatcaatat-3′	22	6645	214

[0794]

TABLE VC
Probe Name Ag1924
			Start
Primers	Sequences	Length	Position	SEQ ID No:
Forward	5′-ctatgggagcagggattcc-3′	19	6546	215
Probe	TET-5′-ctgcacattcatcctcatcagcacaa-3′-	26	6517	216
	TAMRA
Reverse	5′-ccgggtttaccttagactcagt-3′	22	6486	217

[0795]

TABLE VD
Probe Name Ag3108
			Start
Primers	Sequences	Length	Position	SEQ ID No:
Forward	5′attccattgcccaaattaaca-3′	21	4061	218
Probe	TET-5′-ccttcaataacaatattattccagccca-3′-	28	4086	219
	TAMRA
Reverse	5′-actgtgtccattcacactgtca-3′	22	4117	220

[0796]

TABLE VE
Probe Name Ag771
			Start
Primers	Sequences	Length	Position	SEQ ID No:
Forward	5′-gtttcgagcaacacattcaaat-3′	22	4723	221
Probe	TET-5′-tcagaggtatcttctttctgagcatcagca-3′-	30	4693	222
	TAMRA
Reverse	5′-taacgtgttgtccaacaactca-3′	22	4663	223

[0797]

TABLE VF
Probe Name Ag772
			Start
Primers	Sequences	Length	Position	SEQ ID No:
Forward	5′-gtttcgagcaacacattcaaat-3′	22	4723	224
Probe	TET-5′-tcagaggtatcttctttctgagcatcagca-3′	30	4693	225
	TAMRA
Reverse	5′-taacgtgttgtccaacaactca-3′	22	4663	226

[0798]

TABLE VG
Probe Name Ag900
			Start
Primers	Sequences	Length	Position	SEQ ID No:
Forward	5′-aatgccatggggacttactact-3′	22	6572	227
Probe	TET-5′-cctaaaggcctcaccatagctgcaga-3′-	26	6602	228
	TAMRA
Reverse	5′-cccaaagcacactcatcaatat-3′	22	6645	229

[0799]

TABLE VH
Probe Name Ag3899
			Start
Primers	Sequences	Length	Position	SEQ ID No:
Forward	5′-ccattgcccaaattaacatg-3′	20	4064	230
Probe	TET-5′-ccttcaataacaatattattccagccca-3′-	28	4086	231
	TAMRA
Reverse	5′-actgtgtccattcacactgtca-3′	22	4117	232

[0800]

TABLE VI
Probe Name Ag3960
			Start
Primers	Sequences	Length	Position	SEQ ID No:
Forward	5′-aaacacttcatgcatcctctgt-3′	22	6375	233
Probe	TET-5′-cactgggttttaaaattcatgcttca-3′-	26	6426	234
	TAMRA
Reverse	5′-ttactgcgatctcctttggata-3′	22	6453	235

[0801]

TABLE VJ
Probe Name Ag4338
			Start
Primers	Sequences	Length	Position	SEQ ID No:
Forward	5′-tcatgcatcctctgtggaat-3′	20	6382	236
Probe	TET-5′-cactgggttttaaaattcatgcttca-3′-	26	6426	237
	TAMRA
Reverse	5′-ctgattactgcgatctcctttg-3′	22	6457	238

[0802]

TABLE VK
Probe Name Ag343
				SEQ ID
Primers	Sequences	Length	Start Position	No
Forward	5′-attgcacctggtcacctgagt-3′	21	5777	239
Probe	TET-5′-tggccgtccctgtcccgga-3′-TAMRA	19	5752	240
Reverse	5′-gctgtgcgaccatcctgtg-3′	19	5722	241

[0803]

TABLE VL
General_screening_panel_v1.4
	Rel.	Rel.	Rel.		Rel.	Rel.	Rel.
	Exp.(%)	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)	Exp.(%)
	Ag3899,	Ag3960,	Ag4338,		Ag3899,	Ag3960,	Ag4338,
Tissue	Run	Run	Run		Run	Run	Run
Name	219166475	217310662	222550860	Tissue Name	219166475	217310662	222550860
Adipose	1.0	1.9	2.6	Renal ca. TK-	0.0	0.0	0.0
				10
Melanoma*	33.9	72.7	79.0	Bladder	0.6	1.2	1.1
Hs688(A).T
Melanoma*	8.4	22.4	28.9	Gastric ca.	0.0	0.0	0.1
Hs688(B).T				(liver met.)
				NCI-N87
Melanoma*	12.9	24.0	25.3	Gastric ca.	0.0	0.1	0.1
M14				KATO III
Melanoma*	0.1	0.2	0.4	Colon ca. SW-	0.0	0.0	0.0
LOXIMVI				948
Melanoma*	58.6	58.2	77.4	Colon ca.	0.0	0.1	0.2
SK-MEL-5				SW480
Squamous	0.0	0.0	0.1	(Colon ca.*	0.0	0.0	0.0
cell				SW480 met)
carcinoma				SW620
SCC-4
Testis Pool	0.6	0.9	0.9	Colon ca.	0.0	0.0	0.0
				HT29
Prostate	0.2	0.6	0.8	Colon ca.	0.0	0.1	0.1
ca.* (bone				HCT-116
met) PC-3
Prostate	0.4	1.4	2.1	Colon ca.	0.0	0.0	0.1
Pool				CaCo-2
Placenta	0.1	0.3	0.5	Colon cancer	1.2	2.1	3.8
				tissue
Uterus Pool	0.1	0.2	0.6	Colon ca.	0.0	0.0	0.0
				SW1116
Ovarian ca.	0.4	1.2	1.2	Colon ca.	0.0	0.0	0.0
OVCAR-3				Colo-205
Ovarian ca.	0.1	0.8	0.5	Colon ca. SW-	0.0	0.0	0.0
SK-OV-3				48
Ovarian ca.	0.1	0.1	0.2	Colon Pool	0.2	1.5	1.8
OVCAR-4
Ovarian ca.	0.2	0.4	0.6	Small Intestine	0.2	1.2	1.0
OVCAR-5				Pool
Ovarian ca.	0.1	0.1	0.0	Stomach Pool	0.1	0.9	0.8
IGROV-1
Ovarian ca.	0.1	0.2	0.1	Bone Marrow	0.2	0.4	0.6
OVCAR-8				Pool
Ovary	3.6	4.3	5.6	Fetal Heart	1.0	1.3	1.9
Breast ca.	0.5	2.0	2.7	Heart Pool	0.3	0.8	0.7
MCF-7
Breast ca.	0.1	0.2	0.1	Lymph Node	0.4	1.8	2.2
MDA-MB-				Pool
231
Breast ca.	2.6	10.0	7.1	Fetal Skeletal	0.1	0.5	0.7
BT 549				Muscle
Breast ca.	0.2	0.4	0.7	Skeletal	0.2	0.8	0.6
T47D				Muscle Pool
Breast ca.	2.2	15.1	20.3	Spleen Pool	1.1	2.3	2.8
MDA-N
Breast Pool	0.1	1.1	1.9	Thymus Pool	0.6	1.0	1.3
Trachea	1.0	2.8	2.9	CNS cancer	0.8	1.9	2.4
				(glio/astro)
				U87-MG
Lung	0.0	0.5	0.7	CNS cancer	3.0	10.0	10.5
				(glio/astro) U-
				118-MG
Fetal Lung	5.6	21.9	23.7	CNS cancer	0.0	0.0	0.0
				(neuro; met)
				SK-N-AS
Lung ca.	0.0	0.1	0.1	CNS cancer	18.8	37.1	37.1
NCI-N417				(astro) SF-539
Lung ca.	0.0	0.0	0.0	CNS cancer	100.0	100.0	100.0
LX-1				(astro) SNB-75
Lung ca.	0.0	0.1	0.1	CNS cancer	0.0	0.1	0.0
NCI-H146				(glio) SNB-19
Lung ca.	0.0	0.0	0.0	CNS cancer	0.8	2.4	3.1
SHP-77				(glio) SF-295
Lung ca.	0.0	0.0	0.0	Brain	0.0	0.0	0.0
A549				(Amygdala)
				Pool
Lung ca.	0.0	0.0	0.0	Brain	0.0	0.0	0.0
NCI-H526				(cerebellum)
Lung ca.	0.3	0.2	0.3	Brain (fetal)	0.0	0.2	0.3
NCI-H23
Lung ca.	0.1	2.3	1.3	Brain	0.0	0.1	0.3
NCI-H460				(Hippocampus)
				Pool
Lung ca.	0.6	1.7	2.6	Cerebral	0.0	0.1	0.1
HOP-62				Cortex Pool
Lung ca.	0.0	0.1	0.0	Brain	0.0	0.1	0.1
NCI-H522				(Substantia
				nigra) Pool
Liver	0.0	0.1	0.2	Brain	0.0	0.2	0.2
				(Thalamus)
				Pool
Fetal Liver	1.3	1.7	2.4	Brain (whole)	0.0	0.2	0.2
Liver ca.	0.0	0.0	0.0	Spinal Cord	0.1	0.3	0.2
HepG2				Pool
Kidney	0.2	0.7	0.6	Adrenal Gland	0.1	0.4	0.4
Pool
Fetal	1.4	2.4	3.6	Pituitary gland	0.1	0.2	0.5
Kidney				Pool
Renal ca.	0.2	0.8	0.4	Salivary Gland	0.2	0.6	0.7
786-0
Renal ca.	0.0	0.2	0.2	Thyroid	0.1	0.2	0.7
A498				(female)
Renal ca.	0.0	0.0	0.0	Pancreatic ca.	0.0	0.0	0.0
ACHN				CAPAN2
Renal ca.	4.6	4.8	1.3	Pancreas Pool	0.4	1.4	1.4
UO-31

[0804]

TABLE VM
Panel 1
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag343,		Ag343,
	Run		Run
Tissue Name	87586142	Tissue name	87586142
Endothelial cells	0.0	Renal ca. 786-0	0.9
Endothelial cells	0.0	Renal ca. A498	0.0
(treated)
Pancreas	0.3	Renal ca. RXF 393	0.0
Pancreatic ca. CAPAN 2	0.0	Renal ca. ACHN	0.0
Adrenal gland	1.3	Renal ca. UO-31	4.3
Thyroid	4.2	Renal ca. TK-10	0.0
Salivary gland	6.1	Liver	14.6
Pituitary gland	2.6	Liver (fetal)	3.7
Brain (fetal)	0.0	Liver ca.	0.0
		(hepatoblast) HepG2
Brain (whole)	0.0	Lung	12.4
Brain (amygdala)	0.0	Lung (fetal)	29.1
Brain (cerebellum)	0.2	Lung ca. (small cell)	0.0
		LX-1
Brain (hippocampus)	0.0	Lung ca. (small cell)	0.0
		NCI-H69
Brain (substantia nigra)	0.0	Lung ca. (s.cell var.)	0.0
		SHP-77
Brain (thalamus)	0.0	Lung ca. (large	15.7
		cell) NCI-H460
Brain (hypothalamus)	6.5	Lung ca. (non-sm.	0.0
		cell) A549
Spinal cord	2.9	Lung ca. (non-s.cell)	0.0
		NCI-H23
glio/astro U87-MG	6.3	Lung ca. (non-s.cell)	7.2
		HOP-62
glio/astro U-118-MG	10.6	Lung ca. (non-s.cl)	0.0
		NCI-H522
astrocytoma SW1783	1.6	Lung ca. (squam.)	9.2
		SW 900
neuro*; met SK-N-AS	0.0	Lung ca. (squam.)	0.0
		NCI-H596
astrocytoma SF-539	54.7	Mammary gland	72.2
astrocytoma SNB-75	29.7	Breast ca.* (pl.ef)	13.7
		MCF-7
glioma SNB-19	0.0	Breast ca.* (pl.ef)	0.0
		MDA-MB-231
glioma U251	0.6	Breast ca.* (pl.ef)	0.0
		T47D
glioma SF-295	1.8	Breast ca. BT-549	2.6
Heart	18.4	Breast ca. MDA-N	100.0
Skeletal muscle	1.7	Ovary	24.0
Bone marrow	0.0	Ovarian ca. OVCAR-3	0.0
Thymus	7.1	Ovarian ca. OVCAR-4	0.0
Spleen	20.3	Ovarian ca. OVCAR-5	0.6
Lymph node	8.8	Ovarian ca. OVCAR-8	0.0
Colon (ascending)	7.9	Ovarian ca. IGROV-1	0.0
Stomach	20.3	Ovarian ca. (ascites)	0.0
		SK-OV-3
Small intestine	13.7	Uterus	10.3
Colon ca. SW480	0.0	Placenta	10.7
Colon ca.* SW620	0.0	Prostate	7.4
(SW480 met)
Colon ca. HT29	0.0	Prostate ca.* (bone	3.0
		met) PC-3
Colon ca. HCT-116	0.0	Testis	45.7
Colon ca. CaCo-2	0.0	Melanoma	45.7
		Hs688(A).T
Colon ca. HCT-15	0.0	Melanoma* (met)	62.9
		Hs688(B).T
Colon ca. HCC-2998	0.0	Melanoma UACC-62	97.3
Gastric ca.* (liver met)	0.0	Melanoma M14	90.1
NCI-N87
Bladder	5.0	Melanoma LOX	0.5
		IMVI
Trachea	10.6	Melanoma* (met)	95.9
		SK-MEL-5
Kidney	7.2	Melanoma SK-MEL-	72.7
		28
Kidney (fetal)	29.9

[0805]

TABLE VN
Panel 1.2
	Rel.	Rel.		Rel.	Rel.
	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)
	Ag771,	Ag772,		Ag771,	Ag772,
	Run	Run		Run	Run
Tissue Name	116423907	117131093	Tissue Name	116423907	117131093
Endothelial cells	1.4	1.4	Renal ca. 786-0	0.3	0.3
Heart (Fetal)	0.7	1.0	Renal ca. A498	0.0	0.0
Pancreas	0.7	2.0	Renal ca. RXF	0.0	0.0
			393
Pancreatic ca.	0.0	0.0	Renal ca.	0.0	0.0
CAPAN 2			ACHN
Adrenal Gland	2.0	1.9	Renal ca. UO-	4.0	1.4
			31
Thyroid	0.7	2.4	Renal ca. TK-	0.0	0.0
			10
Salivary gland	1.8	3.6	Liver	5.6	8.7
Pituitary gland	1.1	2.8	Liver (fetal)	1.2	2.6
Brain (fetal)	0.0	0.2	Liver ca.	0.0	0.0
			(hepatoblast)
			HepG2
Brain (whole)	0.0	0.3	Lung	3.3	6.2
Brain	0.0	0.0	Lung (fetal)	2.4	7.0
(amygdala)
Brain	0.0	0.0	Lung ca.	0.0	0.0
(cerebellum)			small cell)
			LX-1
Brain	0.0	0.1	Lung ca.	0.3	0.2
(hippocampus)			(small cell)
			NCI-H69
Brain (thalamus)	0.1	0.2	Lung ca. (s.cell	0.0	0.0
			var.) SHP-77
Cerebral Cortex	0.0	0.0	Lung ca. (large	3.2	8.9
			cell) NCI-H460
Spinal cord	0.5	1.2	Lung ca. (non-	0.0	0.0
			sm. cell) A549
glio/astro U87-	1.3	1.2	Lung ca. (non-	0.1	0.2
MG			s.cell) NCI-
H23
glio/astro U-	1.9	2.9	Lung ca. (non-	2.5	5.9
118-MG			s.cell) HOP-62
astrocytoma	0.3	0.5	Lung ca. (non-	0.0	0.1
SW1783			s.cl) NCI-
			H522
neuro*; met SK-	0.0	0.0	Lung ca.	1.0	1.1
N-AS			(squam.) SW
			900
astrocytoma SF-	9.5	11.1	Lung ca.	0.1	0.3
539			(squam.) NCI-
			H596
astrocytoma	4.5	3.6	Mammary	7.3	12.6
SNB-75			gland
glioma SNB-19	0.0	0.0	Breast ca.*	0.7	1.0
			(pl.ef) MCF-7
glioma U251	1.0	0.8	Breast ca.*	0.0	0.0
			(pl.ef) MDA-
			MB-231
glioma SF-295	1.0	0.1	Breast ca.* (pl.	0.0	0.1
			ef) T47D
Heart	7.8	12.3	Breast ca. BT-	0.1	0.2
			549
Skeletal Muscle	4.4	7.7	Breast ca.	27.2	24.3
			MDA-N
Bone marrow	0.0	0.0	Ovary	0.8	1.3
Thymus	0.1	0.2	Ovarian ca.	0.4	0.9
			OVCAR-3
Spleen	1.3	2.7	Ovarian ca.	0.0	0.0
			OVCAR-4
Lymph node	0.4	1.3	Ovarian ca.	0.4	0.6
			OVCAR-5
Colorectal	0.0	0.1	Ovarian ca.	0.0	0.0
Tissue			OVCAR-8
Stomach	1.0	2.7	Ovarian ca.	0.1	0.2
			IGROV-1
Small intestine	2.7	5.6	Ovarian ca.	0.2	0.4
			(ascites) SK-
			OV-3
Colon ca.	0.0	0.0	Uterus	0.5	0.8
SW480
Colon ca.*	0.0	0.0	Placenta	2.2	5.0
SW620 (SW480
met)
Colon ca. HT29	0.0	0.0	Prostate	0.2	0.9
Colon ca. HCT-	0.0	0.0	Prostate ca.*	0.6	2.0
116			(bone met)
Colon ca. CaCo-2	0.0	0.0	PC-3 Testis	1.9	3.6
Colon ca. Tissue	0.8	0.5	Melanoma	5.2	7.8
(ODO3866)			Hs688(A).T
Colon ca. HCC-	0.0	0.0	Melanoma*	10.4	14.1
2998			(met)
			Hs688(B).T
Gastric ca.*	0.0	0.0	Melanoma	100.0	100.0
(liver met) NCI-			UACC-62
N87
Bladder	0.8	1.8	Melanoma	29.3	14.6
			M14
Trachea	1.1	2.5	Melanoma	0.0	0.0
			LOX IMVI
Kidney	0.9	1.6	Melanoma*	30.4	30.4
			(met) SK-
			MEL-5
Kidney (fetal)	4.2	4.8

[0806]

TABLE VO
Panel 1.3D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag3108,		Ag3108,
	Run		Run
Tissue Name	167985250	Tissue Name	167985250
Liver adenocarcinoma	0.2	Kidney (fetal)	4.2
Pancreas	0.1	Renal ca. 786-0	0.5
Pancreatic ca.	0.0	Renal ca. A498	7.7
CAPAN 2
Adrenal gland	0.0	Renal ca. RXF 393	0.5
Thyroid	0.3	Renal ca. ACHN	0.0
Salivary gland	0.0	Renal ca. UO-31	7.9
Pituitary gland	0.3	Renal ca. TK-10	0.0
Brain (fetal)	0.1	Liver	0.2
Brain (whole)	0.3	Liver (fetal)	0.7
Brain (amygdala)	0.0	Liver ca.	0.0
		(hepatoblast) HepG2
Brain (cerebellum)	0.0	Lung	0.4
Brain (hippocampus)	0.0	Lung (fetal)	5.7
Brain	0.2	Lunga ca. (small	0.0
(substantia nigra)		cell) LX-1
Brain (thalamus)	0.0	Lung ca. (small cell)	0.1
		NCI-H69
Cerebral Cortex	0.0	Lung ca. (s.cell	0.1
		var.) SHP-77
Spinal cord	0.5	Lung ca. (large	0.6
		cell) NCI-H460
glio/astro U87-MG	1.2	Lung ca. (non-sm.	0.0
		cell) A549
glio/astro U-118-MG	3.1	Lung ca.	0.4
		(non-s.cell)
		NCI-H23
astrocytoma SW1783	1.4	Lung ca.	1.9
		(non-s.cell)
		HOP-62
neuro*; met SK-N-AS	0.0	Lung ca. (non-s.cl)	0.1
		NCI-H522
astrocytoma SF-539	25.2	Lung ca. (squam.)	1.7
		SW 900
astrocytoma SNB-75	30.8	Lung ca. (squam.)	0.3
		NCI-H596
glioma SNB-19	0.0	Mammary gland	1.2
glioma U251	2.4	Breast ca.* (pl.ef)	1.0
		MCF-7
glioma SF-295	1.1	Breast ca.* (pl.ef)	0.0
		MDA-MB-231
Heart (fetal)	0.8	Breast ca.* (pl.ef)	0.1
		T47D
Heart	1.2	Breast ca. BT-549	0.2
Skeletal muscle (fetal)	0.1	Breast ca. MDA-N	28.7
Skeletal muscle	0.7	Ovary	1.0
Bone marrow	0.0	Ovarian ca.	0.8
		OVCAR-3
Thymus	0.1	Ovarian ca.	0.1
		OVCAR-4
Spleen	0.6	Ovarian ca.	0.8
		OVCAR-5
Lymph node	0.2	Ovarian ca.	0.0
		OVCAR-8
Colorectal	0.0	Ovarian ca.	0.2
		IGROV-1
Stomach	0.2	Ovarian ca.*	0.5
		(ascites) SK-OV-3
Small intestine	0.4	Uterus	0.4
Colon ca. SW480	0.0	Placenta	0.2
Colon ca.*	0.0	Prostate	0.2
SW620(SW480 met)
Colon ca. HT29	0.0	Prostate ca.* (bone	0.7
		met)PC-3
Colon ca. HCT-116	0.0	Testis	0.3
Colon ca. CaCo-2	0.0	Melanoma	12.4
		Hs688(A).T
Colon ca.	4.2	Melanoma* (met)	2.2
tissue(ODO3866)		Hs688(B).T
Colon ca. HCC-2998	0.0	Melanoma UACC-	100.0
		62
Gastric ca.* (liver met)	0.0	Melanoma M14	14.6
NCI-N87
Bladder	0.3	Melanoma LOX	0.2
		IMVI
Trachea	0.4	Melanoma* (met)	20.3
		SK-MEL-5
Kidney	0.4	Adipose	3.3

[0807]

TABLE VP
Panel 2.1
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag3108,		Ag3108,
	Run		Run
Tissue Name	170686074	Tissue Name	170686074
Normal Colon	0.7	Kidney Cancer	0.9
		9010320
Colon cancer	1.3	Kidney margin	9.5
(OD06064)		9010321
Colon cancer margin	0.0	Kidney Cancer	0.6
(OD06064)		8120607
Colon cancer	0.5	Kidney margin	0.7
(OD06159)		8120608
Colon cancer margin	1.8	Normal Uterus	1.7
(OD06159)
Colon cancer	1.6	Uterus Cancer	1.2
(OD06298-08)
Colon cancer margin	0.3	Normal Thyroid	0.1
(OD06298-018)
Colon Cancer	1.6	Thyroid Cancer	0.9
Gr.2 ascend
colon (ODO3921)
Colon Cancer margin	4.6	Thyroid Cancer	1.2
(ODO3921)		A302152
Colon cancer	2.1	Thyroid margin	0.9
metastasis
(OD06104)
Lung margin	2.8	Normal Breast	12.4
(OD06104)
Colon mets to lung	4.5	Breast Cancer	0.9
(OD04451-01)
Lung margin	10.7	Breast Cancer	4.3
(OD04451-02)
Normal Prostate	0.8	Breast Cancer	0.6
		(OD04590-01)
Prostate Cancer	0.7	Breast Cancer Mets	6.6
(OD04410)		(OD04590-03)
Prostate margin	13.6	Breast Cancer	2.1
(OD04410)		Metastasis
Normal Lung	34.2	Breast Cancer	3.3
Invasive poor	9.2	Breast Cancer	4.6
diff. lung
adeno 1		9100266
(ODO4945-01)
Lung margin	6.2	Breast margin	1.5
(ODO4945-03)		9100265
Lung Malignant	11.1	Breast Cancer	2.5
Cancer
(OD03126)		A209073
Lung margin	34.9	Breast margin	9.9
(OD03126)		A2090734
Lung Cancer	25.2	Normal Liver	4.2
(OD05014A)
Lung margin	5.6	Liver Cancer 1026	1.8
(OD05014B)
Lung Cancer	1.5	Liver Cancer 1025	6.1
(OD04237-01)
Lung margin	63.3	Liver Cancer	3.5
(OD04237-02)		6004-T
Ocular Mel	24.3	Liver Tissue 6004-N	0.8
Met to Liver
(ODO4310)
Liver margin	7.6	Liver Cancer	14.2
(ODO4310)		6005-T
Melanoma Mets	100.0	Liver Tissue 6005-N	14.8
to Lung
(OD04321)
Lung margin	20.2	Liver Cancer	1.4
(OD04321)
Normal Kidney	3.6	Normal Bladder	1.7
Kidney Ca,	6.9	Bladder Cancer	1.8
Nuclear grade
2 (OD04338)
Kidney margin	2.1	Bladder Cancer	2.4
(OD04338)
Kidney Ca	1.1	Normal Ovary	7.7
Nuclear grade
1/2 (OD04339)
Kidney margin	0.2	Ovarian Cancer	13.6
(OD04339)
Kidney Ca,	8.8	Ovarian cancer	0.6
Clear cell type
(OD04340)		(OD06145)
Kidney margin	4.5	Ovarian cancer	2.2
(OD04340)		margin (OD06145)
Kidney Ca,	1.3	Normal Stomach	4.1
Nuclear grade
3 (OD04348)
Kidney margin	1.8	Gastric Cancer	1.2
(OD04348)		9060397
Kidney Cancer	0.6	Stomach margin	0.5
(OD04450-01)		9060396
Kidney margin	4.6	Gastric Cancer	7.4
(OD04450-03)		9060395
Kidney Cancer	0.3	Stomach margin	2.6
8120613		9060394
Kidney margin	0.5	Gastric Cancer	4.3
8120614		064005

[0808]

TABLE VQ
Panel 4.1D
	Rel. Exp.(%)	Rel. Exp.(%)	Rel. Exp.(%)	Rel. Exp.(%)
	Ag3899, Run	Ag3960, Run	Ag4338, Run	Ag772, Run
Tissue Name	170120166	170739794	184798156	170188028
Secondary Th1 act	0.0	0.0	0.0	0.0
Secondary Th2 act	0.0	0.0	0.0	0.0
Secondary Tr1 act	0.0	0.0	0.0	0.0
Secondary Th1 rest	0.0	0.0	0.0	0.0
Secondary Th2 rest	0.0	0.0	0.6	0.9
Secondary Tr1 rest	0.0	0.0	0.0	0.0
Primary Th1 act	0.0	0.0	0.0	0.0
Primary Th2 act	0.0	0.0	0.0	0.0
Primary Tr1 act	0.0	0.0	0.0	0.0
Primary Th1 rest	0.0	0.0	0.0	0.0
Primary Th2 rest	0.0	0.0	0.0	0.0
Primary Tr1 rest	0.0	0.4	0.6	0.0
CD45RA CD4	0.3	2.2	2.4	2.5
lymphocyte act
CD45RO CD4	0.0	0.0	0.0	0.0
lymphocyte act
CD8 lymphocyte act	0.0	0.0	0.0	0.0
Secondary CD8	0.0	0.0	0.0	0.0
lymphocyte rest
Secondary CD8	0.0	0.0	0.0	0.0
lymphocyte act
CD4 lymphocyte none	0.0	0.4	0.0	0.0
2ry Th1/Th2/Tr1_anti-	0.0	0.0	1.1	0.0
CD95 CH11
LAK cells rest	0.0	0.0	0.0	0.0
LAK cells IL-2	0.0	0.0	0.0	0.0
LAK cells IL-2 + IL-12	0.0	0.4	0.0	0.0
LAK cells	0.0	0.0	0.0	0.0
IL-2 + IFN gamma
LAK cells IL-2 + IL-18	0.0	0.0	0.0	0.0
LAK cells	0.0	0.0	0.0	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	0.0	0.0	0.0
Two Way MLR 3 day	0.0	0.0	0.0	0.0
Two Way MLR 5 day	0.0	0.0	0.0	0.0
Two Way MLR 7 day	0.0	0.0	0.0	0.0
PBMC rest	0.0	0.0	0.0	0.0
PBMC PWM	0.0	0.0	1.9	0.0
PBMC PHA-L	0.0	0.0	0.0	0.0
Ramos (B cell) none	0.0	0.0	0.0	85.3
Ramos (B cell)	0.0	0.0	0.0	100.0
ionomycin
B lymphocytes PWM	0.0	0.0	0.7	0.0
B lymphocytes CD40L	0.0	0.0	0.9	0.0
and IL-4
EOL-1 dbcAMP	0.0	0.0	0.0	0.0
EOL-1 dbcAMP	0.0	0.0	0.0	0.0
PMA/ionomycin
Dendritic cells none	0.0	0.0	0.0	0.0
Dendritic cells LPS	0.0	0.0	0.0	0.0
Dendritic cells anti-	0.0	0.0	0.0	0.0
CD40
Monocytes rest	0.0	0.0	0.0	0.0
Monocytes LPS	0.0	0.0	0.0	0.0
Macrophages rest	0.0	0.0	0.0	0.0
Macrophages LPS	0.0	0.0	0.0	0.0
HUVEC none	3.2	7.8	10.5	4.5
HUVEC starved	8.1	15.4	14.6	16.5
HUVEC IL-1beta	4.1	3.9	7.4	6.3
HUVEC IFN gamma	15.8	22.8	22.4	16.4
HUVEC	1.0	8.0	8.8	6.0
TNF alpha + IFN gamma
HUVEC	2.9	4.7	8.0	5.9
TNF alpha + IL4
HUVEC IL-11	4.2	10.2	10.4	13.4
Lung Microvascular EC	1.5	8.1	8.4	4.6
none
Lung Microvascular EC	0.0	2.7	3.3	0.0
TNF alpha + IL-1beta
Microvascular Dermal	0.0	1.0	1.6	2.0
EC none
Microsvasular Dermal	0.0	0.0	1.5	0.0
EC
TNF alpha + IL-1beta
Bronchial epithelium	0.4	7.7	5.0	3.6
TNF alpha + IL 1beta
Small airway	0.0	0.0	0.6	0.0
epithelium none
Small airway	0.0	0.5	0.0	0.0
epithelium
TNF alpha + IL-1beta
Coronery artery SMC	8.5	12.7	8.2	14.0
rest
Coronery artery SMC	1.8	10.6	9.8	19.5
TNF alpha + IL-1beta
Astrocytes rest	0.0	0.5	0.8	0.0
Astrocytes	0.5	1.3	2.3	1.0
TNF alpha + IL-1beta
KU-812 (Basophil) rest	1.0	3.1	3.4	6.3
KU-812 (Basophil)	8.0	27.9	28.9	30.8
PMA/ionomycin
CCD1106	0.0	1.6	4.0	1.0
(Keratinocytes) none
CCD1106	0.0	1.1	2.0	1.3
(Keratinocytes)
TNF alpha + IL-1beta
Liver cirrhosis	7.6	18.6	14.2	17.1
NCI-H292 none	0.0	0.0	0.0	0.0
NCI-H292 IL-4	0.0	0.0	0.0	0.0
NCI-H292 IL-9	0.0	0.0	0.0	0.0
NCI-H292 IL-13	0.0	0.5	0.5	0.0
NCI-H292 IFN gamma	0.0	0.0	0.0	0.0
HPAEC none	17.9	21.8	13.2	13.9
HPAEC TNF alpha +	11.3	14.6	13.4	6.3
IL-1beta
Lung fibroblast none	3.4	3.3	5.8	5.2
Lung fibroblast TNF	2.7	2.0	5.3	6.7
alpha + IL-1beta
Lung fibroblast IL-4	4.4	1.8	7.1	9.3
Lung fibroblast IL-9	2.2	3.6	5.2	5.6
Lung fibroblast IL-13	3.9	6.4	6.4	7.7
Lung fibroblast IFN	7.2	6.5	7.8	14.2
gamma
Dermal fibroblast	5.5	11.4	9.3	13.8
CCD1070 rest
Dermal fibroblast	1.9	8.4	9.5	5.9
CCD1070 TNF alpha
Dermal fibroblast	1.5	6.7	6.8	4.1
CCD1070 IL-1beta
Dermal fibroblast IFN	29.5	41.8	17.7	27.5
gamma
Dermal fibroblast IL-4	75.8	69.3	51.8	68.8
Dermal Fibroblasts rest	21.5	36.9	29.5	22.1
Neutrophils TNFa+ LPS	0.0	2.2	0.0	1.6
Neutrophils rest	0.0	6.6	0.4	0.0
Colon	2.0	5.6	2.3	7.1
Lung	100.0	100.0	100.0	79.6
Thymus	0.5	4.4	4.5	4.2
Kidney	3.4	8.4	8.8	9.6

[0809]

TABLE VR
Panel 4D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag3108, Run		Ag3108, Run
Tissue Name	164529436	Tissue Name	164529436
Secondary Th1 act	0.0	HUVEC IL-1beta	3.1
Secondary Th2 act	0.0	HUVEC IFN gamma	7.9
Secondary Tr1 act	0.0	HUVEC	3.5
		TNF alpha + IFN gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	7.1
Secondary Th2 rest	0.2	HUVEC IL-11	4.6
Secondary Tr1 rest	0.3	Lung Microvascular EC	2.3
		none
Primary Th1 act	0.0	Lung Microvascular EC	0.3
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	1.2
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.6
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	3.2
		TNF alpha + IL1beta
Primary Th2 rest	0.3	Small airway epithelium	0.2
		none
Primary Tr1 rest	0.0	Small airway epithelium	0.3
		TNF alpha + IL-1beta
CD45RA CD4	1.5	Coronery artery SMC rest	11.7
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	3.6
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.2
Secondary CD8	0.0	Astrocytes	3.7
lymphocyte rest		TNF alpha + IL-1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	0.6
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	25.7
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	0.6
CD95 CH11		none
LAK cells rest	0.1	CCD1106 (Keratinocytes)	0.4
		TNF alpha + IL-1beta
LAK cells IL-2	0.3	Liver cirrhosis	12.2
LAK cells IL-2 + IL-12	0.0	Lupus kidney	0.2
LAK cells	0.0	NCI-H292 none	0.3
IL-2 + IFN gamma
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-4	0.0
LAK cells	0.0	NCI-H292 IL-9	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IL-13	0.0
Two Way MLR 3 day	0.2	NCI-H292 IFN gamma	0.0
Two Way MLR 5 day	0.0	HPAEC none	11.2
Two Way MLR 7 day	0.0	HPAEC	6.3
		TNF alpha + IL-1beta
PBMC rest	0.0	Lung fibroblast none	1.1
PBMC PWM	0.9	Lung fibroblast	3.0
		TNF alpha + IL-1beta
PBMC PHA-L	0.0	Lung fibroblast IL-4	4.2
Ramos (B cell) none	0.0	Lung fibroblast IL-9	3.5
Ramos (B cell)	0.0	Lung fibroblast IL-13	5.0
ionomycin
B lymphocytes PWM	0.5	Lung fibroblast IFN	6.9
		gamma
B lymphocytes CD40L	0.0	Dermal fibroblast	9.0
and IL-4		CCD1070 rest
EOL-1 dbcAMP	0.0	Dermal fibroblast	10.9
		CCD1070 TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast	3.6
PMA/ionomycin		CCD1070 IL-1beta
Dendritic cells none	0.0	Dermal fibroblast IFN	22.8
		gamma
Dendritic cells LPS	0.0	Dermal fibroblast IL-4	34.2
Dendritic cells anti-	0.0	IBD Colitis 2	0.2
CD40
Monocytes rest	0.0	IBD Crohn's	3.2
Monocytes LPS	0.0	Colon	13.0
Macrophages rest	0.0	Lung	100.0
Macrophages LPS	0.0	Thymus	16.2
HUVEC none	6.0	Kidney	3.7
HUVEC starved	19.3

[0810] CNS_neurodegeneration_v1.0 Summary: Ag3899/Ag3960/Ag4338/Ag772 Expression of the CG94013-01 gene is low/undetectable (CTs >34) across all of the samples on this panel.

[0811] General_screening_panel_v1.4 Summary: Ag3899/Ag3960/Ag4338 Results of three experiments with two different primer and probe sets are in excellent agreement, with highest expression of the CG94013-01 gene in CNS cancer (astro) SNB-75 cell line (CTs=23-26). In addition, high expression of this gene is seen in CNS cancer cell lines, colon cancer tissue, renal cancer cell line UO-31, breast cancer and melanoma cell lines. Therefore, expression of this gene can be used to distinguish these samples from other samples in the panel and also as marker for detection of these cancers. 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 these cancers.

[0812] Among tissues with metabolic or endocrine function, this gene is expressed at low 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.

[0813] Interestingly, this gene is expressed at much higher levels in fetal liver (CTs=31-32) and lung (CTs=28) when compared to corresponding adult tissue(CTs=33-35). This observation suggests that expression of this gene can be used to distinguish these fetal tissues from corresponding adult tissues.

[0814] Panel 1 Summary: Ag343 Highest expression of the CG94013-01 gene is detected in breast cancer MDA-N cell line (CTs=26). In addition high expression of this gene is also observed in melanoma, astrocytoma, and lung cancer cell lines. Please see panel 1.4 for the utility of this gene.

[0815] Panel 1.2 Summary: Ag771/Ag772 Two experiments produce results that are in excellent agreement, with highest expression of this gene in a melanoma cell line (CTs=25). High levels of expression are also seen in clusters of samples from melanoma, breast and brain cancer cell lines. Thus, expression of this gene could be used to differentiate between the melanoma sample and other samples on this panel and 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 melanoma, breast and brain cancers. Data from a third experiment with Ag772 are not included. The results suggest that there were experimental difficulties with this run.

[0816] Panel 1.3D Summary: Ag3108 Highest expression of the CG94013-01 gene is detected in melanoma (met) Hs688(B).T cell line (CT=27). In addition, expression of this gene is also seen in melanoma, breast cancer, lung cancer, astrocytoma cell lines and colon cancer well to moderately differentiated (ODO3866) tissue. Please see panel 1.4 for the utility of this gene.

[0817] Panel 2.1 Summary: Ag3108 Highest expression of the CG94013-01 gene is detected in melanoma metastasis sample (CT=29). In addition, expression of this gene is higher in metastasis breast cancer (OD04590-03) (CT=33) as compared to breast cancer (OD04590-01) (CT=36.7). Thus, expression of this gene can be used to distinguish these two samples from each other and also as marker for cancer metastasis. Please see panel 1.4 for further utility of this gene.

[0818] Panel 4.1D Summary: Ag3899/Ag3960/Ag4338 Results of three experiments with two different primer and probe sets are in excellent agreement, with highest expression of the CG94013-01 gene in lung (CT=30-31). In addition, significant expression of this gene is seen in HUVEC cells, lung fibroblast and dermal fibroblasts. Therefore, antibody or small molecule therapies designed with the protein encoded for by this gene could be important in the treatment of inflammatory lung disorders such as chronic obstructive pulmonary disease, asthma, allergy and emphysema and skin disorders including psoriasis.

[0819] In addition, low expression of this gene is also seen in kidney. 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.

[0820] Results from one experiment with probe and primer set Ag772 are not included. The amp plot suggests that there were experimental difficulties with this run.

[0821] Panel 4D Summary: Ag3108 Highest expression of the CG94013-01 gene in lung (CT=28.6). In addition, significant expression of this gene is seen in HPAEC cells, HUVEC cells, lung fibroblast,TNFalpha+ILlbeta treated bronchial epithelium and dermal fibroblasts. Therefore, antibody or small molecule therapies designed with the protein encoded for by this gene could be important in the treatment of inflammatory lung disorders such as chronic obstructive pulmonary disease, asthma, allergy and emphysema and skin disorders including psoriasis.

[0822] In addition, low expression of this gene is also seen in kidney and colon. Therefore, antibody or small molecule therapies designed with the protein encoded for by this gene be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis, as well as, inflammatory bowel diseases such as Crohns.

[0823] Interestingly, expression of this gene is stimulated in PMA/ionomycin treated basophils (CT=30) as compared to resting basophils (CT=36). Basophils release histamines and other biological modifiers in reponse to allergens and play an important role in the pathology of asthma and hypersensitivity reactions. Therefore, therapeutics designed against the putative protein encoded by this gene may reduce or inhibit inflammation by blocking basophil function in these diseases. In addition, these cells are a reasonable model for the inflammatory cells that take part in various inflammatory lung and bowel diseases, such as asthma, Crohn's disease, and ulcerative colitis. Therefore, therapeutics that modulate the function of this gene product may reduce or eliminate the symptoms of patients suffering from asthma, Crohn's disease, and ulcerative colitis.

[0824] Ag1924 Results from one experiment with the CG94013-01 gene are not included. The amp plot indicates that there were experimental difficulties with this run.

[0825] W. NOV26a (CG93871-01: Fibullin)

[0826] Expression of gene CG93871-01 was assessed using the primer-probe sets Ag1294b, Ag746 and Ag905, described in Tables WA, WB and WC. Results of the RTQ-PCR runs are shown in Tables WD, WE, WF, WG, WH and WI.

TABLE WA
Probe Name Ag1294b
			Start
Primers	Sequences	Length	Position	SEQ ID No:
Forward	5′-cattggcagctacaagtgttc-3′	21	688	242
Probe	TET-5′-ctgtcgaactggcttccaccttcat-3′-	25	709	243
	TAMRA
Reverse	5′-cctccgacactcgtttacatc-3′	21	755	244

[0827]

TABLE WB
Probe Name Ag746
			Start
Primers	Sequences	Length	Position	SEQ ID No:
Forward	5′-gcattggcagctacaagtgt-3′	20	687	245
Probe	TET-5′-ctgtcgaactggcttccaccttcat-3′-TAMRA	25	709	246
Reverse	5′-cctccgacactcgtttacatc-3′	21	755	247

[0828]

TABLE WC
Probe Name Ag905
			Start
Primers	Sequences	Length	Position	SEQ ID No:
Forward	5′-cattggcagctacaagtgttc-3′	21	688	248
Probe	TET-5═-ctgtcgaactggcttccaccttcat-3′-TAMRA	25	709	249
Reverse	5′-cctccgacactcgtttacatc-3′	21	755	250

[0829]

TABLE WD
AI_comprehensive panel_v1.0
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag1294b,		Ag1294b, Run
Tissue Name	Run 249007981	Tissue Name	249007981
110967 COPD-F	6.6	112427 Match Control	30.8
		Psoriasis-F
110980 COPD-F	16.6	112418 Psoriasis-M	4.6
110968 COPD-M	3.9	112723 Match Control	23.8
		Psoriasis-M
110977 COPD-M	31.6	112419 Psoriasis-M	2.7
110989 Emphysema-F	45.1	112424 Match Control	1.9
		Psoriasis-M
110992 Emphysema-F	7.2	112420 Psoriasis-M	4.9
110993 Emphysema-F	5.8	112425 Match Control	25.9
		Psoriasis-M
110994 Emphysema-F	3.3	104689 (MF) OA	12.9
		Bone-Backus
110995 Emphysema-F	2.0	104690 (MF) Adj	3.7
		“Normal” Bone-Backus
110996 Emphysema-F	3.1	104691 (MF) OA	6.9
		Synovium-Backus
110997 Asthma-M	3.7	104692 (BA) OA	21.3
		Cartilage-Backus
111001 Asthma-F	2.8	104694 (BA) OA	6.6
		Bone-Backus
111002 Asthma-F	5.3	104695 (BA) Adj	2.3
		“Normal” Bone-
		Backus
111003 Atopic	6.1	104696 (BA) OA	5.7
Asthma-F		Synovium-Backus
111004 Atopic	3.4	104700 (SS) OA Bone-	6.2
Asthma-F		Backus
111005 Atopic	3.9	104701 (SS) Adj	3.8
Asthma-F		“Normal” Bone-
		Backus
111006 Atopic	2.4	104702 (SS) OA	15.4
Asthma-F		Synovium-Backus
111417 Allergy-M	6.6	117093 OA Cartilage	18.0
		Rep7
112347 Allergy-M	3.3	112672 OA Bone5	90.1
112349 Normal Lung-F	3.2	112673 OA	63.7
		Synovium5
112357 Normal	100.0	112674 OA Synovial	32.3
Lung-F		Fluid cells5
112354 Normal	58.6	117100 OA Cartilage	3.3
Lung-M		Rep14
112374 Crohns-F	7.5	112756 OA Bone9	7.0
112389 Match	3.5	112757 OA	12.2
Control Crohns-F		Synovium9
112375 Crohns-F	5.1	112758 OA Synovial	3.9
		Fluid Cells9
112732 Match	0.5	117125 RA Cartilage	4.6
Control Crohns-F		Rep2
112725 Crohns-M	10.6	113492 Bone2 RA	2.4
112387 Match	3.5	113493 Synovium2	1.1
Control Crohns-M		RA
112378 Crohns-M	1.7	113494 Syn Fluid	1.4
		Cells RA
112390 Match	55.5	113499 Cartilage4 RA	1.4
Control Crohns-M
112726 Crohns-M	3.6	113500 Bone4 RA	0.5
112731 Match	13.9	113501 Synovium4	1.7
Control Crohns-M		RA
112380 Ulcer Col-F	13.7	113502 Syn Fluid	1.8
		Cells4 RA
112734 Match	5.6	113495 Cartilage3 RA	1.6
Control Ulcer Col-F
112384 Ulcer Col-F	3.9	113496 Bone3 RA	1.1
112737 Match	3.3	113497 Synovium3	0.0
Control Ulcer Col-F		RA
112386 Ulcer Col-F	0.0	113498 Syn Fluid	0.6
		Cells3 RA
112738 Match	0.0	117106 Normal	4.5
Control Ulcer Col-F		Cartilage Rep20
112381 Ulcer Col-M	4.2	113663 Bone3 Normal	6.7
112735 Match	18.2	113664 Synovium3	1.2
Control Ulcer Col-M		Normal
112382 Ulcer Col-M	4.2	113665 Syn Fluid	0.9
		Cells3 Normal
112394 Match	0.0	117107 Normal	1.3
Control Ulcer Col-M		Cartilage Rep22
112383 Ulcer Col-M	12.2	113667 Bone4 Normal	11.8
112736 Match	2.0	113668 Synovium4	12.0
Control Ulcer Col-M		Normal
112423 Psoriasis-F	3.9	113669 Syn Fluid	10.7
		Cells4 Normal

[0830]

TABLE WE
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag1294b,		Ag1294b,
	Run		Run
Tissue Name	206231468	Tissue Name	206231468
AD 1 Hippo	11.2	Control (Path) 3	1.5
		Temporal Ctx
AD 2 Hippo	22.5	Control (Path) 4	19.2
		Temporal Ctx
AD 3 Hippo	4.7	AD 1 Occipital Ctx	15.8
AD 4 Hippo	8.7	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	37.6	AD 3 Occipital Ctx	1.2
AD 6 Hippo	100.0	AD 4 Occipital Ctx	17.8
Control 2 Hippo	28.7	AD 5 Occipital Ctx	8.7
Control 4 Hippo	30.4	AD 6 Occipital Ctx	12.3
Control (Path) 3	6.9	Control 1 Occipital	0.0
Hippo		Ctx
AD 1 Temporal Ctx	16.3	Control 2 Occipital	27.4
		Ctx
AD 2 Temporal Ctx	31.6	Control 3 Occipital	5.4
		Ctx
AD 3 Temporal Ctx	3.8	Control 4 Occipital	6.7
		Ctx
AD 4 Temporal Ctx	10.9	Control (Path) 1	56.3
		Occipital Ctx
AD 5 Inf Temporal	34.6	Control (Path) 2	10.4
Ctx		Occipital Ctx
AD 5 Sup Temporal	19.6	Control (Path) 3	1.2
Ctx		Occipital Ctx
AD 6 Inf Temporal	73.7	Control (Path) 4	6.3
Ctx		Occipital Ctx
AD 6 Sup Temporal	81.2	Control 1 Parietal	6.4
Ctx		Ctx
Control 1 Temporal	1.2	Control 2 Parietal	39.5
Ctx		Ctx
Control 2 Temporal	15.5	Control 3 Parietal	4.4
Ctx		Ctx
Control 3 Temporal	5.9	Control (Path) 1	17.6
Ctx		Parietal Ctx
Control 4 Temporal	7.9	Control (Path) 2	17.6
Ctx		Parietal Ctx
Control (Path) 1	41.8	Control (Path) 3	0.0
Temporal Ctx		Parietal Ctx
Control (Path) 2	26.2	Control (Path) 4	26.4
Temporal Ctx		Parietal Ctx

[0831]

TABLE WF
Panel 1.2
	Rel.	Rel.		Rel.	Rel.
	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)
	Ag746,	Ag746,		Ag746,	Ag746,
	Run	Run		Run	Run
Tissue Name	115163442	119442272	Tissue Name	115163442	119442272
Endothelial cells	12.3	5.9	Renal ca. 786-0	0.0	0.0
Heart (Fetal)	0.0	0.0	Renal ca. A498	0.0	0.0
Pancreas	0.0	0.0	Renal ca. RXF	0.0	0.0
			393
Pancreatic ca.	0.0	0.0	Renal ca.	0.0	0.0
CAPAN 2			ACHN
Adrenal Gland	0.0	0.2	Renal ca. UO-	0.0	0.0
			31
Thyroid	0.1	0.0	Renal ca. TK-	0.0	0.0
			10
Salivary gland	0.0	0.0	Liver	32.8	53.2
Pituitary gland	0.2	0.1	Liver (fetal)	72.7	100.0
Brain (fetal)	2.4	16.0	Liver ca.	100.0	94.0
			(hepatoblast)
			HepG2
Brain (whole)	0.0	0.3	Lung	0.0	0.0
Brain	0.0	0.0	Lung (fetal)	0.0	0.0
(amygdala)
Brain	0.0	0.0	Lung ca.	0.0	0.0
(cerebellum)			(small cell)
			LX-1
Brain	0.0	0.0	Lung ca.	0.0	0.0
(hippocampus)			(small cell)
			NCI-H69
Brain (thalamus)	0.0	0.0	Lung ca. (s.cell	0.0	0.0
			var.) SHP-77
Cerebral Cortex	0.0	0.0	Lung ca. (large	0.0	0.0
			cell) NCI-H460
Spinal cord	0.0	0.0	Lung ca. (non-	0.0	0.0
			sm. cell) A549
glio/astro U87-	0.0	0.0	Lung ca. (non-	0.0	0.0
MG			s.cell) NCI-
			H23
glio/astro U-	0.0	0.0	Lung ca. (non-	0.0	0.0
118-MG			s.cell) HOP-62
astrocytoma	0.0	0.0	Lung ca. (non-	63.7	90.1
SW1783			NCI-
			H522
neuro*; met SK-	0.0	0.2	Lung ca.	0.0	0.0
N-AS			(squam.) SW
			900
astrocytoma SF-	0.0	0.0	Lung ca.	0.0	0.0
539			(squam.) NCI-
			H596
astrocytoma	0.0	0.0	Mammary	0.7	3.6
SNB-75			gland
glioma SNB-19	0.0	0.0	Breast ca.*	0.0	0.0
			(pl.ef) MCF-7
glioma U251	0.0	0.0	Breast ca.*	0.0	0.0
			(pl.ef) MDA-
			MB-231
glioma SF-295	0.0	0.0	Breast ca.* (pl.	0.0	0.0
			ef) T47D
Heart	0.0	0.0	Breast ca. BT-	0.0	0.0
			549
Skeletal Muscle	0.0	0.0	Breast ca.	0.0	0.0
			MDA-N
Bone marrow	0.0	0.0	Ovary	0.5	11.7
Thymus	1.2	2.8	Ovarian ca.	0.0	0.0
			OVCAR-3
Spleen	0.0	0.0	Ovarian ca.	0.0	0.0
			OVCAR-4
Lymph node	0.0	0.0	Ovarian ca.	0.0	0.0
			OVCAR-5
Colorectal	0.0	0.0	Ovarian ca.	0.0	0.0
Tissue			OVCAR-8
Stomach	0.0	0.0	Ovarian ca.	0.0	0.0
			IGROV-1
Small intestine	0.0	0.0	Ovarian ca.	0.0	0.0
			(ascites) SK-
			OV-3
Colon ca.	0.0	0.0	Uterus	0.0	0.0
SW480
Colon ca.*	1.1	1.9	Placenta	34.4	39.5
SW620 (SW480
met)
Colon ca. HT29	0.0	0.0	Prostate	0.0	0.0
Colon ca. HCT-	0.0	0.0	Prostate ca.*	0.0	0.0
116			(bone met) PC-3
Colon ca. CaCo-2	46.3	56.6	Testis	1.0	3.5
Colon ca. Tissue	0.0	0.0	Melanoma	0.0	0.0
(ODO3866)			Hs688(A).T
Colon ca. HCC-	0.0	0.0	Melanoma*	0.0	0.0
2998			(met)
			Hs688(B).T
Gastric ca.*	0.0	0.0	Melanoma	0.0	0.0
(liver met) NCI-			UACC-62
N87
Bladder	0.0	0.0	Melanoma	0.0	0.0
			M14
Trachea	0.0	0.0	Melanoma	0.0	0.0
			LOX IMVI
Kidney	0.0	0.0	Melanoma*	0.0	0.0
			(met) SK-
			MEL-5
Kidney (fetal)	0.1	0.9

[0832]

TABLE WG
Panel 2D
	Rel. Exp. (%)	Rel. Exp. (%)		Rel. Exp. (%)	Rel. Exp. (%)
	Ag746, Run	Ag746, Run		Ag746, Run	Ag746, Run
Tissue Name	147127131	148019631	Tissue Name	147127131	148019631
Normal Colon	18.3	21.8	Kidney	6.5	6.4
			Margin
			8120608
CC Well to Mod	16.5	23.7	Kidney Cancer	2.2	0.7
Diff (OD03866)			8120613
CC Margin	3.1	0.0	Kidney	6.3	3.0
(OD03866)			Margin		3.0
			8120614
CC Gr.2	0.0	0.8	Kidney Cancer	10.9	16.5
rectosigmoid			9010320
(OD03868)
CC Margin	0.5	2.0	Kidney	9.0	11.3
(OD03868)			Margin
			9010321
CC Mod Diff	1.2	2.3	Normal Uterus	4.3	6.3
(OD03920)
CC Margin	1.3	2.6	Uterus Cancer	13.4	17.7
(OD03920)			064011
CC Gr.2 ascend	3.4	4.4	Normal	9.1	14.9
colon			Thyroid
(OD03921)
CC Margin	1.3	0.0	Thyroid	6.4	5.9
(OD03921)			Cancer
			064010
CC from Partial	8.4	1.9	Thyroid	4.4	5.1
Hepatectomy			Cancer
(OD04309)			A302152
Mets
Liver Margin	49.7	41.5	Thyroid	12.0	22.1
(OD04309)			Margin
			A302153
Colon mets to	0.3	5.3	Normal Breast	9.9	14.3
lung
(OD04451-01)
Lung Margin	0.0	1.8	Breast Cancer	0.4	0.2
(OD04451-02)			(OD04566)
Normal Prostate	9.1	12.1	Breast Cancer	5.3	3.9
6546-1			(OD04590-01)
Prostate Cancer	2.0	9.7	Breast Cancer	4.0	10.4
(OD04410)			Mets
			(OD04590-03)
Prostate Margin	16.8	20.3	Breast Cancer	7.2	4.4
(OD04410)			Metastasis
			(OD04655-05)
Prostate Cancer	13.5	14.4	Breast Cancer	5.2	3.3
(OD04720-01)			064006
Prostate Margin	14.0	22.4	Breast Cancer	12.1	18.6
(OD04720-02)			1024
Normal Lung	6.8	11.7	Breast Cancer	2.7	5.3
061010			9100266
Lung Met to	1.8	0.7	Breast Margin	5.0	5.8
Muscle			9100265
(OD04286)
Muscle Margin	11.5	13.1	Breast Cancer	0.5	1.8
(OD04286)			A209073
Lung Malignant	1.5	6.0	Breast Margin	1.7	0.4
Cancer			A209073
(OD03126)
Lung Margin	4.8	2.4	Normal Liver	39.5	47.0
(OD03126)
Lung Cancer	4.2	2.3	Liver Cancer	4.2	0.6
(OD04404)			064003
Lung Margin	9.0	10.4	Liver Cancer	66.4	74.2
(OD04404)			1025
Lung Cancer	0.3	0.0	Liver Cancer	36.1	42.6
(OD04565)			1026
Lung Margin	0.4	0.3	Liver Cancer	100.0	100.
(OD04565)			6004-T
Lung Cancer	10.7	11.1	Liver Tissue	22.8	34.4
(OD04237-01)			6004-N
Lung Margin	4.9	5.4	Liver Cancer	39.2	35.4
(OD04237-02)			6005-T
Ocular Mel Met	10.5	11.9	Liver Tissue	33.2	38.2
to Liver			6005-N
(OD04310)
Liver Margin	22.4	32.8	Normal	6.6	4.9
(OD04310)			Bladder
Melanoma Mets	0.0	0.0	Bladder	1.0	4.8
to Lung			Cancer 1023
(OD04321)
Lung Margin	0.6	0.0	Bladder	2.6	0.7
(OD04321)			Cancer
			A302173
Normal Kidney	5.3	5.3	Bladder	0.0	0.7
			Cancer
			(OD04718-01)
Kidney Ca,	39.8	43.8	Bladder	3.5	14.4
Nuclear grade 2			Normal
(OD04338)			Adjacent
			(OD04718-03)
Kidney Margin	4.8	6.4	Normal Ovary	50.7	47.3
(OD04338)
Kidney Ca	3.0	0.3	Ovarian	10.2	7.4
Nuclear grade			Cancer
½ (OD04339)			064008
Kidney Margin	5.4	10.0	Ovarian	73.7	80.7
(OD04339)			Cancer
			(OD04768-07)
Kidney Ca, Clear	18.2	19.2	Ovary Margin	2.6	0.8
cell type			(OD04768-08)
(OD04340)
Kidney Margin	9.0	10.4	Normal	2.9	2.9
(OD04340)			Stomach
Kidney Ca,	5.2	8.3	Gastric Cancer	0.0	1.1
Nuclear grade 3			9060358
(OD04348)
Kidney Margin	6.9	4.7	Stomach	2.4	0.3
(OD04348)			Margin
			9060359
Kidney Cancer	41.8	45.4	Gastric Cancer	0.5	1.1
(OD04622-01)			9060395
Kidney Margin	1.9	1.4	Stomach	5.2	2.0
(OD04622-03)			Margin
			9060394
Kidney Cancer	9.2	6.2	Gastric Cancer	3.4	7.0
(OD04450-01)			9060397
Kidney Margin	10.2	9.0	Stomach	1.4	0.0
(OD04450-03)			Margin
			9060396
Kidney Cancer	2.2	1.7	Gastric Cancer	1.3	6.0
8120607			064005

[0833]

TABLE WH
Panel 4.1D
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag1294b, Run		Ag1294b, Run
Tissue Name	200065765	Tissue Name	200065765
Secondary Th1 act	15.3	HUVEC IL-1beta	5.6
Secondary Th2 act	7.2	HUVEC IFN gamma	21.9
Secondary Tr1 act	5.5	HUVEC	35
		TNF alpha + IFN gamma
Secondary Th1 rest	6.7	HUVEC TNF alpha + IL4	31.2
Secondary Th2 rest	1.0	HUVEC IL-11	17.7
Secondary Tr1 rest	1.3	Lung Microvascular EC	65.1
		none
Primary Th1 act	26.6	Lung Microvascular EC	34.4
		TNF alpha + IL-1beta
Primary Th2 act	34.2	Microvascular Dermal EC	42.3
		none
Primary Tr1 act	40.3	Microsvasular Dermal EC	16.7
		TNFaIpha + IL-1beta
Primary Th1 rest	0.3	Bronchial epithelium	2.4
		TNF alpha + IL1beta
Primary Th2 rest	0.5	Small airway epithelium	1.7
		none
Primary Tr1 rest	0.0	Small airway epithelium	2.5
		TNF alpha + IL-1beta
CD45RA CD4	7.7	Coronery artery SMC rest	9.0
lymphocyte act
CD45RO CD4	10.9	Coronery artery SMC	5.2
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	11.0	Astrocytes rest	2.1
Secondary CD8	11.8	Astrocytes	2.2
lymphocyte rest		TNF alpha + IL-1beta
Secondary CD8	4.7	KU-812 (Basophil) rest	10.2
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil) rest	11.1
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	1.7	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.6
		TNF alpha + IL-1beta
LAK cells IL-2	3.1	Liver cirrhosis	6.8
LAK cells IL-2 + IL-12	2.9	NCI-H292 none	21.3
LAK cells IL-2 + IFN	0.5	NCI-H292 IL-4	11.5
gamma
LAK cells IL-2 + IL-18	0.5	NCI-H292 IL-9	13.8
LAK cells	1.0	NCI-H292 IL-13	19.9
PMA/ionomycin
NK Cells IL-2 rest	1.4	NCI-H292 IFN gamma	7.3
Two Way MLR 3 day	3.1	HPAEC none	20.4
Two Way MLR 5 day	5.0	HPAEC TNF alpha + IL-	21.5
		1beta
Two Way MLR 7 day	4.7	Lung fibroblast none	23.5
PBMC rest	0.6	Lung fibroblast TNF	8.8
		alpha + IL-1beta
PBMC PWM	11.5	Lung fibroblast IL-4	21.2
PBMC PHA-L	7.2	Lung fibroblast IL-9	16.8
Ramos (B cell) none	1.8	Lung fibroblast IL-13	33.2
Ramos (B cell)	3.4	Lung fibroblast IFN	19.1
ionomycin		gamma
B lymphocytes PWM	20.2	Dermal fibroblast	2.9
		CCD1070 rest
B lymphocytes CD40L	12.2	Dermal fibroblast	0.0
and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	1.5	Dermal fibroblast	1.5
		CCD1070 IL-1beta
EOL-1 dbcAMP	1.1	Dermal fibroblast IFN	45.1
PMA/ionomycin		gamma
Dendritic cells none	8.5	Dermal fibroblast IL-4	100.0
Dendritic cells LPS	6.4	Dermal Fibroblasts rest	53.6
Dendritic cells anti-	8.7	Neutrophils TNFa + LPS	1.5
CD40
Monocytes rest	0.0	Neutrophils rest	10.2
Monocytes LPS	1.1	Colon	1.5
Macrophages rest	8.8	Lung	1.7
Macrophages LPS	0.0	Thymus	40.1
HUVEC none	10.1	Kidney	1.5
HUVEC starved	7.6

[0834]

TABLE WI
Panel 4D
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	Ag1294b,	Ag1294b,		Ag1294b,	Ag1294b,
	Run	Run		Run	Run
Tissue Name	138944262	139408252	Tissue Name	138944262	139408252
Secondary Th1 act	10.9	7.7	HUVEC IL-1beta	4.1	1.7
Secondary Th2 act	6.4	8.0	HUVEC IFN	21.0	13.7
			gamma
Secondary Tr1 act	11.3	9.3	HUVEC TNF	2.8	0.6
			alpha + IFN
			gamma
Secondary Th1 rest	3.4	2.7	HUVEC TNF	30.8	25.7
			alpha + IL4
Secondary Th2 rest	1.5	2.5	HUVEC IL-11	11.6	7.3
Secondary Tr1 rest	1.4	2.0	Lung	24.1	20.0
			Microvascular EC
			none
Primary Th1 act	48.0	46.0	Lung	8.0	12.2
			Microvascular EC
			TNFalpha + IL-
			1beta
Primary Th2 act	38.7	27.7	Microvascular	64.6	45.7
			Dermal EC none
Primary Tr1 act	72.2	55.5	Microsvasular	18.4	11.7
			Dermal EC
			TNFalpha + IL-
			1beta
Primary Th1 rest	3.1	2.3	Bronchial	5.2	5.4
			epithelium
			TNFalpha +
			IL1beta
Primary Th2 rest	1.0	0.8	Small airway	4.0	3.2
			epithelium none
Primary Tr1 rest	1.1	0.5	Small airway	8.2	4.5
			epithelium
			TNFalpha + IL-
			1beta
CD45RA CD4	2.9	1.8	Coronery artery	5.8	6.3
lymphocyte act			SMC rest
CD45RO CD4	18.6	12.2	Coronery artery	4.5	5.1
lymphocyte act			SMC TNFalpha +
			IL-1beta
CD8 lymphocyte	17.8	6.8	Astrocytes rest	0.8	0.5
act
Secondary CD8	6.8	6.0	Astrocytes	3.6	1.9
lymphocyte rest			TNF alpha +IL-
			1beta
Secondary CD8	5.5	4.1	KU-812	16.0	11.1
lymphocyte act			(Basophil) test
CD4 lymphocyte	0.0	0.2	KU-812	12.3	9.5
none			(Basophil)
			PMA/ionomycin
2ry	2.9	3.1	CCD1106	0.0	0.5
Th1/Th2/Tr1_anti-			(Keratinocytes)
CD95 CH11			none
LAK cells rest	1.4	0.3	CCD1106	0.7	0.4
			(Keratinocytes)
			TNFalpha + IL-
			1beta
LAK cells IL-2	3.8	2.2	Liver cirrhosis	8.4	3.8
LAK cells IL-	3.0	0.8	Lupus kidney	2.0	3.2
2 + IL-12
LAK cells IL-	2.0	1.7	NCI-H292 none	21.9	25.7
2 + IFN gamma
LAK cells IL-2+	0.5	0.2	NCI-H292 IL-4	15.7	12.3
IL-18
LAK cells	0.7	1.3	NCI-H292 IL-9	20.6	14.7
PMA/ionomycin
NK Cells IL-2 rest	0.7	0.7	NCI-H292 IL-13	8.3	5.7
Two Way MLR 3	1.1	2.5	NCI-H292 IFN	5.1	8.2
day			gamma
Two Way MLR5	2.5	2.8	HPAEC none	18.7	23.8
day
Two Way MLR7	4.5	5.0	HPAEC TNF	11.9	12.9
day			alpha + IL-1 beta
PBMC rest	0.0	0.0	Lung fibroblast	15.7	13.5
			none
PBMC PWM	41.8	29.1	Lung fibroblast
			TNFalpha +IL-1
			beta
PBMC PHA-L	34.4	21.8	Lung fibroblast	25.0	16.6
			IL-4
Ramos (B cell)	4.7	2.4	Lung fibroblast	14.7	15.8
none			IL-9
Ramos (B cell)	9.2	5.8	Lung fibroblast	40.3	32.5
ionomycin			IL-13
B lymphocytes	51.8	51.4	Lung fibroblast	15.4	17.4
PWM			IFN gamma
B lymphocytes	10.2	12.3	Dermal fibroblast	0.5	0.9
CD40L and IL-4			CCD1070 rest
EOL-1 dbcAMP	0.3	0.2	Dermal fibroblast	0.9	0.8
			CCD1070 TNF
			alpha
EOL-1 dbcAMP	0.4	1.8	Dermal fibroblast	0.6	0.6
PMA/ionomycin			CCD1070 IL-1
			beta
Dendritic cells	6.7	3.8	Dermal fibroblast	32.1	18.4
none			IFN gamma
Dendritic cells LPS	4.7	3.1	Dermal fibroblast	100.0	100.0
			IL-4
Dendritic cells anti-	6.0	5.6	IBD Colitis 2	0.0	0.0
CD40
Monocytes rest	0.0	0.0	IBD Crohn's	0.3	0.8
Monocytes LPS	0.7	0.8	Colon	1.4	0.5
Macrophages rest	19.8	9.9	Lung	0.5	0.8
Macrophages LPS	0.7	0.5	Thymus	2.9	4.3
HUVEC none	9.3	10.2	Kidney	65.5	47.3
HUVEC starved	19.2	13.1

[0835] AI_comprehensive panel_v1.0 Summary: Ag1294b Expression of the CG93871-01 gene in this panel confirms expression of this gene in cells involved in the immune response. Highest expression of this gene is seen in normal lung (CT=30.5). Please see Panel 4D for discussion of utility of this gene in inflammation.

[0836] CNS_neurodegeneration_v1.0 Summary: Ag1294b This panel does not show differential expression of the CG56153-01 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain. 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.

[0837] Panel 1.2 Summary: Ag746 Two experiments with the same probe and primer set produce results that are in excellent agreement, with highest expression of the CG93871-01 gene in a liver cancer cell line (CTs=27). High levels of expression are also seen in fetal and adult liver tissue, a colon cancer cell line and a lung cancer cell line. Thus, expression of this gene could be used to differentiate liver derived samples, the colon cancer cell line and the lung cancer cell line from other samples on this panel. Expression of this gene could also be used as a diagnostic marker to detect the presence of colon and lung cancers.

[0838] Moderate expression is also seen in the fetal brain, placenta, and endothelial cells.

[0839] Panel 2D Summary: Ag746 Two experiments with the same probe and primer set produce results that are in excellent agreement, with highest expression of the CG93871-01 gene in liver cancer (CTs=31). The prominent expression in liver derived tissue is consistent with the results in Panel 1.2. Moderate levels of expression are also evident in samples from ovarian cancer and kidney cancer. Furthermore, expression of this gene is higher in these cancers than in the normal adjacent tissue. Thus, expression of this gene could be used to differentiate between liver derived samples and other samples on this panel and as a marker to detect the presence of liver, kidney, and ovarian cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of liver, kidney, and ovarian cancers.

[0840] Panel 4.1D Summary: Ag1294b Results from this experiment are in agreement with the expression profile in Panel 4D, with highest expression of the CG93871-01 gene in this experiment in IL-4 treated dermal fibroblasts (CT=29.9). In addition, this experiment shows low but significant levels of expression in resting neutrophils (CT=33.2), a sample absent in Panel 4D. Please see Panel 4D for discussion of utility of this gene in inflammation.

[0841] Panel 4D Summary: Ag1294b Two experiments with the same probe and primer set produce results that are in excellent agreement, with highest expression of the CG93871-01 gene in IL-4 treated dermal fibroblasts (CTs=30). In addition, this gene is expressed at moderate levels in IFN gamma stimulated dermal fibroblasts, activated lung fibroblasts, HPAECs, lung and dermal microvasculature, activated small airway and bronchial epithelium, activated NCI-H292 cells, acutely activated T cells, and activated B cells.

[0842] Based on these levels of expression in T cells, activated B cells and cells in lung and skin, therapeutics that block the function of this gene product may be useful as therapeutics that reduce or eliminate the symptoms in patients with autoimmune and inflammatory diseases in which activated B cells present antigens in the generation of the aberrant immune response and in treating T-cell mediated diseases, including Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, allergy, emphysema, rheumatoid arthritis, or psoriasis.

Example D

Identification of Single Nucleotide Polymorphisms in NOVX Nucleic Acid Sequences

[0843] 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 can be 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.

[0844] 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.

[0845] 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.

[0846] 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 Nucleotide Polymorphisms by Real-time Pyrophosphate DNA Sequencing. Genome Research. 10 (8) 1249-1265, 2000).

[0847] 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.

Results

NOV2a SNP Data

[0848] Two polymorphic variants of NOV2a have been identified and are shown in Table 28A.

	TABLE 28A
	Nucleotides	Amino Acids
	Base			Base
	Position			Position
Variant	of	Wild-		of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13374244	1115	G	A	363	Ser	Asn
13377677	1895	A	G	623	Lys	Arg

NOV11a SNP Data

[0849] Two polymorphic variants of NOV11a have been identified and are shown in Table 28B.

	TABLE 28B
	Nucleotides	Amino Acids
	Base			Base
	Position			Position
Variant	of	Wild-		of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13377547	564	T	C	188	Ile	Ile
13375667	779	G	A	260	Ser	Asn

NOV12a SNP Data

[0850] Eleven polymorphic variants of NOV12a have been identified and are shown in Table 28C.

	TABLE 28C
	Nucleotides	Amino Acids
	Base			Base
	Position			Position
Variant	of	Wild-		of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13376026	1212	C	T	402	Thr	Ile
13376027	1459	C	T	484	Ala	Ala
13376028	1575	C	T	523	Pro	Leu
13376020	1699	C	T	564	Asn	Asn
13376021	1733	C	T	576	Gln	End
13376029	1826	C	T	607	His	Tyr
13376022	1859	A	C	618	Ser	Arg
13376019	1896	C	T	630	Ser	Phe
13376023	1984	C	T	659	Thr	Thr
13376024	2522	C	G	839	Pro	Ala
13376025	2865	G	A	953	Arg	Gln

NOV17a SNP Data

[0851] Eleven polymorphic variants of NOV17a have been identified and are shown in Table 28D.

	TABLE 28D
	Nucleotides	Amino Acids
	Base			Base
	Position			Position
Variant	of	Wild-		of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13377723	612	C	T	32	Ser	Leu
13377722	774	G	A	86	Ser	Asn
13377727	1875	A	T	453	Gln	Leu
13377716	8402	T	C	2629	Ser	Pro
13377717	8502	C	T	2662	Ser	Phe
13377718	8520	T	C	2668	Val	Ala
13377719	8676	T	C	2720	Ile	Thr
13377720	9006	T	C	2830	Val	Ala
13377724	10626	G	A	3370	Ser	Asn
13377725	10719	G	A	3401	Gly	Asp
13377721	15055	A	G	4846	Arg	Arg

NOV19a SNP Data

[0852] Three polymorphic variants of NOV19a have been identified and are shown in Table 28E.

	TABLE 28E
	Nucleotides	Amino Acids
	Base			Base
	Position			Position
Variant	of	Wild-		of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13377733	1458	C	T	399	Ala	Val
13377732	1987	T	C	0
13377731	2121	T	C	0

NOV20a SNP Data

[0853] Two polymorphic variants of NOV20a have been identified and are shown in Table 28F.

	TABLE 28F
	Nucleotides	Amino Acids
	Base			Base
	Position			Position
Variant	of	Wild-		of	Wild-
No.	SNP	type	Variant	SNP	type	Variant
13377737	436	A	G	99	Asn	Asp
13377736	591	T	C	150	Ala	Ala

Other Embodiments

[0854] 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. 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 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 1-46; 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 1-46, 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) the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1-46; d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1-46, 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).

2. The polypeptide of claim 1 that is a naturally occurring allelic variant of the sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1-46.

3. The polypeptide of claim 2, wherein said allelic variant comprises an amino acid sequence that is the translation of a nucleic acid sequence differing 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 1-46.

4. The polypeptide of claim 1 that is a variant polypeptide described therein, wherein any amino acid specified in the chosen sequence is changed to provide a conservative substitution.

5. A pharmaceutical composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable carrier.

6. A kit comprising in one or more containers, the pharmaceutical composition of claim 5.

7. 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 said therapeutic is the polypeptide of claim 1.

8. 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.

9. A method for determining the presence of or predisposition to a disease associated with altered levels 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 amount of said polypeptide in the sample of step (a) 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, said 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 said disease.

10. A method for modulating the activity of the polypeptide of claim 1, the method comprising introducing a cell sample expressing the polypeptide of said claim with an antibody that binds to said polypeptide in an amount sufficient to modulate the activity of the polypeptide.

11. The method of claim 10, wherein said subject is a human.

12. 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 of SEQ ID NO:2n, wherein n is an integer between 1-46; 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 1-46, 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 1-46; d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1-46, 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 1-46, 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.

13. The nucleic acid molecule of claim 12, wherein the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring alletic nucleic acid variant.

14. The nucleic acid molecule of claim 12 that encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant.

15. The nucleic acid molecule of claim 12, 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 1-46.

16. The nucleic acid molecule of claim 12, 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 1-46; 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 1-46, 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 1-46; 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 1-46, 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.

17. The nucleic acid molecule of claim 12, 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 1-46, or a complement of said nucleotide sequence.

18. The nucleic acid molecule of claim 12, wherein the nucleic acid molecule comprises a nucleotide sequence in which any nucleotide specified in the coding sequence of the chosen 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 in the chosen coding sequence are so changed, an isolated second polynucleotide that is a complement of the first polynucleotide, or a fragment of any of them.

19. A vector comprising the nucleic acid molecule of claim 12.

20. The vector of claim 19, further comprising a promoter operably linked to said nucleic acid molecule.

21. A cell comprising the vector of claim 20.

22. A method for determining the presence or amount of the nucleic acid molecule of claim 12 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.

23. The method of claim 22 wherein presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type.

24. The method of claim 23 wherein the cell or tissue type is cancerous.

25. A method for determining the presence of or predisposition to a disease associated with altered levels of the nucleic acid molecule of claim 12 in a first mammalian subject, the method comprising: a) measuring the amount of the nucleic acid in a sample from the first mammalian subject; and b) comparing the amount of said nucleic acid in the sample of step (a) to the amount 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 the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

26. An antibody that binds immunospecifically to the polypeptide of claim 1.

27. The antibody of claim 26, wherein said antibody is a monoclonal antibody.

28. The antibody of claim 26, wherein the antibody is a humanized antibody.

29. The antibody of claim 26, wherein the antibody is a fully human antibody

30. The antibody of claim 26, wherein the dissociation constant for the binding of the polypeptide to the antibody is less than 1×10−9 M.

31. The antibody of claim 26, wherein the antibody neutralizes an activity of the polypeptide.

32. A pharmaceutical composition comprising the antibody of claim 26 and a pharmaceutically acceptable carrier.

33. A kit comprising in one or more containers, the pharmaceutical composition of claim 29.

34. 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 said therapeutic is a NOVX antibody.

35. A method of treating or preventing a NOVX-associated disorder, said method comprising administering to a subject in which such treatment or prevention is desired the antibody of claim 26 in an amount sufficient to treat or prevent said NOVX-associated disorder in said subject.

36. A method of treating a pathological state in a mammal, the method comprising administering to the mammal the antibody of claim 26 in an amount sufficient to alleviate the pathological state.

37. A method of treating or preventing a pathology associated with the polypeptide of claim 1, said method comprising administering to a subject in which such treatment or prevention is desired a NOVX antibody in an amount sufficient to treat or prevent said pathology in said subject.

38. The method of claim 37, wherein the subject is a human.