Novel compounds

Abstract

Polypeptides and polynucleotides of the genes set forth in Table I and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing polypeptides and polynucleotides of the genes set forth in Table I in diagnostic assays.

Description

FIELD OF INVENTION

[0001] This invention relates to newly identified polypeptides and polynucleotides encoding such polypeptides, to their use in diagnosis and in identifying compounds that may be agonists, antagonists that are potentially useful in therapy, and to production of such polypeptides and polynucleotides. The polynucleotides and polypeptides of the present invention also relate to proteins with signal sequences which allow them to be secreted extracellularly or membrane-associated (hereinafter often referred collectively as secreted proteins or secreted polypeptides).

BACKGROUND OF THE INVENTION

[0002] The drug discovery process is currently undergoing a fundamental revolution as it embraces “functional genomics”, that is, high throughput genome- or gene-based biology. This approach as a means to identify genes and gene products as therapeutic targets is rapidly superseding earlier approaches based on “positional cloning”. A phenotype, that is a biological function or genetic disease, would be identified and this would then be tracked back to the responsible gene, based on its genetic map position.

[0003] Functional genomics relies heavily on high-throughput DNA sequencing technologies and the various tools of bioinformatics to identify gene sequences of potential interest from the many molecular biology databases now available. There is a continuing need to identify and characterise further genes and their related polypeptides/proteins, as targets for drug discovery.

[0004] Proteins and polypeptides that are naturally secreted into blood, lymph and other body fluids, or secreted into the cellular membrane are of primary interest for pharmaceutical research and development. The reason for this interest is the relative ease to target protein therapeutics into their place of action (body fluids or the cellular membrane). The natural pathway for protein secretion into extracellular space is the endoplasmic reticulum in eukaryotes and the inner membrane in prokaryotes (Palade, 1975, Science, 189, 347; Milstein, Brownlee, Harrison, and Mathews, 1972, Nature New Biol., 239, 117; Blobel, and Dobberstein, 1975, J. Cell. Biol., 67, 835). On the other hand, there is no known natural pathway for exporting a protein from the exterior of the cells into the cytosol (with the exception of pinocytosis, a mechanism of snake venom toxin intrusion into cells). Therefore targeting protein therapeutics into cells poses extreme difficulties.

[0005] The secreted and membrane-associated proteins include but are not limited to all peptide hormones and their receptors (including but not limited to insulin, growth hormones, chemokines, cytokines, neuropeptides, integrins, kallikreins, lamins, melanins, natriuretic hormones, neuropsin, neurotropins, pituitiary hormones, pleiotropins, prostaglandins, secretogranins, selecting, thromboglobulins, thymosins), the breast and colon cancer gene products, leptin, the obesity gene protein and its receptors, serum albumin, superoxide dismutase, spliceosome proteins, 7TM (transmembrane) proteins also called as G-protein coupled receptors, immunoglobulins, several families of serine proteinases (including but not limited to proteins of the blood coagulation cascade, digestive enzymes), deoxyribonuclease I, etc.

[0006] Therapeutics based on secreted or membrane-associated proteins approved by FDA or foreign agencies include but are not limited to insulin, glucagon, growth hormone, chorionic gonadotropin, follicle stimulating hormone, luteinizing hormone, calcitonin, adrenocorticotropic hormone (ACTH), vasopressin, interleukines, interferones, immunoglobulins, lactoferrin (diverse products marketed by several companies), tissue-type plasminogen activator (Alteplase by Genentech), hyaulorindase (Wydase by Wyeth-Ayerst), dornase alpha (Pulmozyme\ by Genentech), Chymodiactin (chymopapain by Knoll), alglucerase (Ceredase by Genzyme), streptokinase (Kabikinase by Pharmacia) (Streptase by Astra), etc. This indicates that secreted and membrane-associated proteins have an established, proven history as therapeutic targets. Clearly, there is a need for identification and characterization of further secreted and membrane-associated proteins which can play a role in preventing, ameliorating or correcting dysfunction or disease, including but not limited to diabetes, breast-, prostate-, colon cancer and other malignant tumors, hyper- and hypotension, obesity, bulimia, anorexia, growth abnormalities, asthma, manic depression, dementia, delirium, mental retardation, Huntington's disease, Tourette's syndrome, schizophrenia, growth, mental or sexual development disorders, and dysfunctions of the blood cascade system including those leading to stroke. The proteins of the present invention which include the signal sequences are also useful to further elucidate the mechanism of protein transport which at present is not entirely understood, and thus can be used as research tools.

SUMMARY OF THE INVENTION

[0007] The present invention relates to particular polypeptides and polynucleotides of the genes set forth in Table I, including recombinant materials and methods for their production. Such polypeptides and polynucleotides are of interest in relation to methods of treatment of certain diseases, including, but not limited to, the diseases set forth in Tables III and V, hereinafter referred to as “diseases of the invention”. In a further aspect, the invention relates to methods for identifying agonists and antagonists (e.g., inhibitors) using the materials provided by the invention, and treating conditions associated with imbalance of polypeptides and/or polynucleotides of the genes set forth in Table I with the identified compounds. In still a further aspect, the invention relates to diagnostic assays for detecting diseases associated with inappropriate activity or levels the genes set forth in Table I. Another aspect of the invention concerns a polynucleotide comprising any of the nucleotide sequences set forth in the Sequence Listing and a polypeptide comprising a polypeptide encoded by the nucleotide sequence. In another aspect, the invention relates to a polypeptide comprising any of the polypeptide sequences set forth in the Sequence Listing and recombinant materials and methods for their production. Another aspect of the invention relates to methods for using such polypeptides and polynucleotides. Such uses include the treatment of diseases, abnormalities and disorders (hereinafter simply referred to as diseases) caused by abnormal expression, production, function and or metabolism of the genes of this invention, and such diseases are readily apparent by those skilled in the art from the homology to other proteins disclosed for each attached sequence. In still another aspect, the invention relates to methods to identify agonists and antagonists using the materials provided by the invention, and treating conditions associated with the imbalance with the identified compounds. Yet another aspect of the invention relates to diagnostic assays for detecting diseases associated with inappropriate activity or levels of the secreted proteins of the present invention.

DESCRIPTION OF THE INVENTION

[0008] In a first aspect, the present invention relates to polypeptides the genes set forth in Table I. Such polypeptides include:

[0009] (a) an isolated polypeptide encoded by a polynucleotide comprising a sequence set forth in the Sequence Listing, herein when referring to polynucleotides or polypeptides of the Sequence Listing, a reference is also made to the Sequence Listing referred to in the Sequence Listing;

[0010] (b) an isolated polypeptide comprising a polypeptide sequence having at least 95%, 96%, 97%, 98%, or 99% identity to a polypeptide sequence set forth in the Sequence Listing;

[0011] (c) an isolated polypeptide comprising a polypeptide sequence set forth in the Sequence Listing;

[0012] (d) an isolated polypeptide having at least 95%, 96%, 97%, 98%, or 99% identity to a polypeptide sequence set forth in the Sequence Listing;

[0013] (e) a polypeptide sequence set forth in the Sequence Listing; and

[0014] (f) an isolated polypeptide having or comprising a polypeptide sequence that has an Identity Index of 0.95, 0.96, 0.97, 0.98, or 0.99 compared to a polypeptide sequence set forth in the Sequence Listing;

[0015] (g) fragments and variants of such polypeptides in (a) to (f).

[0016] Polypeptides of the present invention are believed to be members of the gene families set forth in Table II. They are therefore of therapeutic and diagnostic interest for the reasons set forth in Tables III and V. The biological properties of the polypeptides and polynucleotides of the genes set forth in Table I are hereinafter referred to as “the biological activity” of polypeptides and polynucleotides of the genes set forth in Table I. Preferably, a polypeptide of the present invention exhibits at least one biological activity of the genes set forth in Table I.

[0017] Polypeptides of the present invention also include variants of the aforementioned polypeptides, including all allelic forms and splice variants. Such polypeptides vary from the reference polypeptide by insertions, deletions, and substitutions that may be conservative or non-conservative, or any combination thereof. Particularly preferred variants are those in which several, for instance from 50 to 30, from 30 to 20, from 20 to 10, from 10 to 5, from 5 to 3, from 3 to 2, from 2 to 1 or I amino acids are inserted, substituted or deleted, in any combination.

[0018] Preferred fragments of polypeptides of the present invention include an isolated polypeptide comprising an amino acid sequence having at least 30, 50 or 100 contiguous amino acids from an amino acid sequence set forth in the Sequence Listing, or an isolated polypeptide comprising an amino acid sequence having at least 30, 50 or 100 contiguous amino acids truncated or deleted from an amino acid sequence set forth in the Sequence Listing. Preferred fragments are biologically active fragments that mediate the biological activity of polypeptides and polynucleotides of the genes set forth in Table I, including those with a similar activity or an improved activity, or with a decreased undesirable activity. Also preferred are those fragments that are antigenic or immunogenic in an animal, especially in a human.

[0019] Fragments of a polypeptide of the invention may be employed for producing the corresponding full-length polypeptide by peptide synthesis; therefore, these variants may be employed as intermediates for producing the full-length polypeptides of the invention. A polypeptide of the present invention may be in the form of the “mature” protein or may be a part of a larger protein such as a precursor or a fusion protein. It is often advantageous to include an additional amino acid sequence that contains secretory or leader sequences, pro-sequences, sequences that aid in purification, for instance multiple histidine residues, or an additional sequence for stability during recombinant production.

[0020] Polypeptides of the present invention can be prepared in any suitable manner, for instance by isolation form naturally occurring sources, from genetically engineered host cells comprising expression systems (vide infra) or by chemical synthesis, using for instance automated peptide synthesizers, or a combination of such methods. Means for preparing such polypeptides are well understood in the art.

[0021] In a further aspect, the present invention relates to polynucleotides of the genes set forth in Table I. Such polynucleotides include:

[0022] (a) an isolated polynucleotide comprising a polynucleotide sequence having at least 95%, 96%, 97%, 98%, or 99% identity to a polynucleotide sequence set forth in the Sequence Listing;

[0023] (b) an isolated polynucleotide comprising a polynucleotide set forth in the Sequence Listing;

[0024] (c) an isolated polynucleotide having at least 95%, 96%, 97%, 98%, or 99% identity to a polynucleotide set forth in the Sequence Listing;

[0025] (d) an isolated polynucleotide set forth in the Sequence Listing;

[0026] (e) an isolated polynucleotide comprising a polynucleotide sequence encoding a polypeptide sequence having at least 95%, 96%, 97%, 98%, or 99% identity to a polypeptide sequence set forth in the Sequence Listing;

[0027] (f) an isolated polynucleotide comprising a polynucleotide sequence encoding a polypeptide set forth in the Sequence Listing;

[0028] (g) an isolated polynucleotide having a polynucleotide sequence encoding a polypeptide sequence having at least 95%, 96%, 97%, 98%, or 99% identity to a polypeptide sequence set forth in the Sequence Listing;

[0029] (h) an isolated polynucleotide encoding a polypeptide set forth in the Sequence Listing;

[0030] (i) an isolated polynucleotide having or comprising a polynucleotide sequence that has an Identity Index of 0.95, 0.96, 0.97, 0.98, or 0.99 compared to a polynucleotide sequence set forth in the Sequence Listing;

[0031] (j) an isolated polynucleotide having or comprising a polynucleotide sequence encoding a polypeptide sequence that has an Identity Index of 0.95, 0.96, 0.97, 0.98, or 0.99 compared to a polypeptide sequence set forth in the Sequence Listing; and

[0032] polynucleotides that are fragments and variants of the above mentioned polynucleotides or that are complementary to above mentioned polynucleotides, over the entire length thereof.

[0033] Preferred fragments of polynucleotides of the present invention include an isolated polynucleotide comprising an nucleotide sequence having at least 15, 30, 50 or 100 contiguous nucleotides from a sequence set forth in the Sequence Listing, or an isolated polynucleotide comprising a sequence having at least 30, 50 or 100 contiguous nucleotides truncated or deleted from a sequence set forth in the Sequence Listing.

[0034] Preferred variants of polynucleotides of the present invention include splice variants, allelic variants, and polymorphisms, including polynucleotides having one or more single nucleotide polymorphisms (SNPs).

[0035] Polynucleotides of the present invention also include polynucleotides encoding polypeptide variants that comprise an amino acid sequence set forth in the Sequence Listing and in which several, for instance from 50 to 30, from 30 to 20, from 20 to 10, from 10 to 5, from 5 to 3, from 3 to 2, from 2 to 1 or 1 amino acid residues are substituted, deleted or added, in any combination.

[0036] In a further aspect, the present invention provides polynucleotides that are RNA transcripts of the DNA sequences of the present invention. Accordingly, there is provided an RNA polynucleotide that:

[0037] (a) comprises an RNA transcript of the DNA sequence encoding a polypeptide set forth in the Sequence Listing;

[0038] (b) is a RNA transcript of a DNA sequence encoding a polypeptide set forth in the Sequence Listing;

[0039] (c) comprises an RNA transcript of a DNA sequence set forth in the Sequence Listing; or

[0040] (d) is a RNA transcript of a DNA sequence set forth in the Sequence Listing; and RNA polynucleotides that are complementary thereto.

[0041] The polynucleotide sequences set forth in the Sequence Listing show homology with the polynucleotide sequences set forth in Table II. A polynucleotide sequence set forth in the Sequence Listing is a cDNA sequence that encodes a polypeptide set forth in the Sequence Listing. A polynucleotide sequence encoding a polypeptide set forth in the Sequence Listing may be identical to a polypeptide encoding a sequence set forth in the Sequence Listing or it may be a sequence other than a sequence set forth in the Sequence Listing, which, as a result of the redundancy (degeneracy) of the genetic code, also encodes a polypeptide set forth in the Sequence Listing. A polypeptide of a sequence set forth in the Sequence Listing is related to other proteins of the gene families set forth in Table II, having homology and/or structural similarity with the polypeptides set forth in Table II. Preferred polypeptides and polynucleotides of the present invention are expected to have, inter alia, similar biological functions/properties to their homologous polypeptides and polynucleotides. Furthermore, preferred polypeptides and polynucleotides of the present invention have at least one activity of the genes set forth in Table I.

[0042] Polynucleotides of the present invention may be obtained using standard cloning and screening techniques from a cDNA library derived from mRNA from the tissues set forth in Table IV (see for instance, Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989)). Polynucleotides of the invention can also be obtained from natural sources such as genomic DNA libraries or can be synthesized using well known and commercially available techniques.

[0043] When polynucleotides of the present invention are used for the recombinant production of polypeptides of the present invention, the polynucleotide may include the coding sequence for the mature polypeptide, by itself, or the coding sequence for the mature polypeptide in reading frame with other coding sequences, such as those encoding a leader or secretory sequence, a pre-, or pro- or prepro- protein sequence, or other fusion peptide portions. For example, a marker sequence that facilitates purification of the fused polypeptide can be encoded. In certain preferred embodiments of this aspect of the invention, the marker sequence is a hexa-histidine peptide, as provided in the pQE vector (Qiagen, Inc.) and described in Gentz et al., Proc Natl Acad Sci USA (1989) 86:821-824, or is an HA tag. A polynucleotide may also contain non-coding 5′ and 3′ sequences, such as transcribed, non-translated sequences, splicing and polyadenylation signals, ribosome binding sites and sequences that stabilize mRNA.

[0044] Polynucleotides that are identical, or have sufficient identity to a polynucleotide sequence set forth in the Sequence Listing, may be used as hybridization probes for cDNA and genomic DNA or as primers for a nucleic acid amplification reaction (for instance, PCR). Such probes and primers may be used to isolate full-length cDNAs and genomic clones encoding polypeptides of the present invention and to isolate cDNA and genomic clones of other genes (including genes encoding paralogs from human sources and orthologs and paralogs from other species) that have a high sequence similarity to sequences set forth in the Sequence Listing, typically at least 95% identity. Preferred probes and primers will generally comprise at least 15 nucleotides, preferably, at least 30 nucleotides and may have at least 50, if not at least 100 nucleotides. Particularly preferred probes will have between 30 and 50 nucleotides. Particularly preferred primers will have between 20 and 25 nucleotides.

[0045] A polynucleotide encoding a polypeptide of the present invention, including homologs from other species, may be obtained by a process comprising the steps of screening a library under stringent hybridization conditions with a labeled probe having a sequence set forth in the Sequence Listing or a fragment thereof, preferably of at least 15 nucleotides; and isolating full-length cDNA and genomic clones containing the polynucleotide sequence set forth in the Sequence Listing. Such hybridization techniques are well known to the skilled artisan. Preferred stringent hybridization conditions include overnight incubation at 42° C. in a solution comprising: 50% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5× Denhardt's solution, 10% dextran sulfate, and 20 microgram/ml denatured, sheared salmon sperm DNA; followed by washing the filters in 0.1×SSC at about 65° C. Thus the present invention also includes isolated polynucleotides, preferably with a nucleotide sequence of at least 100, obtained by screening a library under stringent hybridization conditions with a labeled probe having the sequence set forth in the Sequence Listing or a fragment thereof, preferably of at least 15 nucleotides.

[0046] The skilled artisan will appreciate that, in many cases, an isolated cDNA sequence will be incomplete, in that the region coding for the polypeptide does not extend all the way through to the 5′ terminus. This is a consequence of reverse transcriptase, an enzyme with inherently low “processivity” (a measure of the ability of the enzyme to remain attached to the template during the polymerisation reaction), failing to complete a DNA copy of the mRNA template during first strand cDNA synthesis.

[0047] There are several methods available and well known to those skilled in the art to obtain full-length cDNAs, or extend short cDNAs, for example those based on the method of Rapid Amplification of cDNA ends (RACE) (see, for example, Frohman et al., Proc Nat Acad Sci USA 85, 8998-9002, 1988). Recent modifications of the technique, exemplified by the Marathon (trade mark) technology (Clontech Laboratories Inc.) for example, have significantly simplified the search for longer cDNAs. In the Marathon (trade mark) technology, cDNAs have been prepared from mRNA extracted from a chosen tissue and an ‘adaptor’ sequence ligated onto each end. Nucleic acid amplification (PCR) is then carried out to amplify the “missing” 5′ end of the cDNA using a combination of gene specific and adaptor specific oligonucleotide primers. The PCR reaction is then repeated using ‘nested’ primers, that is, primers designed to anneal within the amplified product (typically an adapter specific primer that anneals further 3′ in the adaptor sequence and a gene specific primer that anneals further 5′ in the known gene sequence). The products of this reaction can then be analyzed by DNA sequencing and a full-length cDNA constructed either by joining the product directly to the existing cDNA to give a complete sequence, or carrying out a separate full-length PCR using the new sequence information for the design of the 5′ primer.

[0048] Recombinant polypeptides of the present invention may be prepared by processes well known in the art from genetically engineered host cells comprising expression systems. Accordingly, in a further aspect, the present invention relates to expression systems comprising a polynucleotide or polynucleotides of the present invention, to host cells which are genetically engineered with such expression systems and to the production of polypeptides of the invention by recombinant techniques. Cell-free translation systems can also be employed to produce such proteins using RNAs derived from the DNA constructs of the present invention.

[0049] For recombinant production, host cells can be genetically engineered to incorporate expression systems or portions thereof for polynucleotides of the present invention. Polynucleotides may be introduced into host cells by methods described in many standard laboratory manuals, such as Davis et al., Basic Methods in Molecular Biology (1986) and Sambrook et al.(ibid). Preferred methods of introducing polynucleotides into host cells include, for instance, calcium phosphate transfection, DEAE-dextran mediated transfection, transvection, micro-injection, cationic lipid-mediated transfection, electroporation, transduction, scrape loading, ballistic introduction or infection.

[0050] Representative examples of appropriate hosts include bacterial cells, such as Streptococci, Staphylococci, E. coli, Streptomyces and Bacillus subtilis cells; fungal cells, such as yeast cells and Aspergillus cells; insect cells such as Drosophila S2 and Spodoptera Sf9 cells; animal cells such as CHO, COS, HeLa, C127, 3T3, BHK, HEK 293 and Bowes melanoma cells; and plant cells.

[0051] A great variety of expression systems can be used, for instance, chromosomal, episomal and virus-derived systems, e.g., vectors derived from bacterial plasmids, from bacteriophage, from transposons, from yeast episomes, from insertion elements, from yeast chromosomal elements, from viruses such as baculoviruses, papova viruses, such as SV40, vaccinia viruses, adenoviruses, fowl pox viruses, pseudorabies viruses and retroviruses, and vectors derived from combinations thereof, such as those derived from plasmid and bacteriophage genetic elements, such as cosmids and phagemids. The expression systems may contain control regions that regulate as well as engender expression. Generally, any system or vector that is able to maintain, propagate or express a polynucleotide to produce a polypeptide in a host may be used. The appropriate polynucleotide sequence may be inserted into an expression system by any of a variety of well-known and routine techniques, such as, for example, those set forth in Sambrook et al., (ibid). Appropriate secretion signals may be incorporated into the desired polypeptide to allow secretion of the translated protein into the lumen of the endoplasmic reticulum, the periplasmic space or the extracellular environment. These signals may be endogenous to the polypeptide or they may be heterologous signals.

[0052] If a polypeptide of the present invention is to be expressed for use in screening assays, it is generally preferred that the polypeptide be produced at the surface of the cell. In this event, the cells may be harvested prior to use in the screening assay. If the polypeptide is secreted into the medium, the medium can be recovered in order to recover and purify the polypeptide. If produced intracellularly, the cells must first be lysed before the polypeptide is recovered.

[0053] Polypeptides of the present invention can be recovered and purified from recombinant cell cultures by well-known methods including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxylapatite chromatography and lectin chromatography. Most preferably, high performance liquid chromatography is employed for purification. Well known techniques for refolding proteins may be employed to regenerate active conformation when the polypeptide is denatured during intracellular synthesis, isolation and/or purification.

[0054] Polynucleotides of the present invention may be used as diagnostic reagents, through detecting mutations in the associated gene. Detection of a mutated form of a gene is characterized by the polynucleotides set forth in the Sequence Listing in the cDNA or genomic sequence and which is associated with a dysfunction. Will provide a diagnostic tool that can add to, or define, a diagnosis of a disease, or susceptibility to a disease, which results from under-expression, over-expression or altered spatial or temporal expression of the gene. Individuals carrying mutations in the gene may be detected at the DNA level by a variety of techniques well known in the art.

[0055] Nucleic acids for diagnosis may be obtained from a subject's cells, such as from blood, urine, saliva, tissue biopsy or autopsy material. The genomic DNA may be used directly for detection or it may be amplified enzymatically by using PCR, preferably RT-PCR, or other amplification techniques prior to analysis. RNA or cDNA may also be used in similar fashion. Deletions and insertions can be detected by a change in size of the amplified product in comparison to the normal genotype. Point mutations can be identified by hybridizing amplified DNA to labeled nucleotide sequences of the genes set forth in Table I. Perfectly matched sequences can be distinguished from mismatched duplexes by RNase digestion or by differences in melting temperatures. DNA sequence difference may also be detected by alterations in the electrophoretic mobility of DNA fragments in gels, with or without denaturing agents, or by direct DNA sequencing (see, for instance, Myers et al., Science (1985) 230:1242). Sequence changes at specific locations may also be revealed by nuclease protection assays, such as RNase and S1 protection or the chemical cleavage method (see Cotton et al., Proc Natl Acad Sci USA (1985) 85: 4397-4401).

[0056] An array of oligonucleotides probes comprising polynucleotide sequences or fragments thereof of the genes set forth in Table I can be constructed to conduct efficient screening of e.g., genetic mutations. Such arrays are preferably high density arrays or grids. Array technology methods are well known and have general applicability and can be used to address a variety of questions in molecular genetics including gene expression, genetic linkage, and genetic variability, see, for example, M. Chee et al., Science, 274, 610-613 (1996) and other references cited therein.

[0057] Detection of abnormally decreased or increased levels of polypeptide or mRNA expression may also be used for diagnosing or determining susceptibility of a subject to a disease of the invention. Decreased or increased expression can be measured at the RNA level using any of the methods well known in the art for the quantitation of polynucleotides, such as, for example, nucleic acid amplification, for instance PCR, RT-PCR, RNase protection, Northern blotting and other hybridization methods. Assay techniques that can be used to determine levels of a protein, such as a polypeptide of the present invention, in a sample derived from a host are well-known to those of skill in the art. Such assay methods include radio-immunoassays, competitive-binding assays, Western Blot analysis and ELISA assays.

[0058] Thus in another aspect, the present invention relates to a diagnostic kit comprising:

[0059] (a) a polynucleotide of the present invention, preferably the nucleotide sequence set forth in the Sequence Listing, or a fragment or an RNA transcript thereof;

[0060] (b) a nucleotide sequence complementary to that of (a);

[0061] (c) a polypeptide of the present invention, preferably the polypeptide set forth in the Sequence Listing or a fragment thereof; or

[0062] (d) an antibody to a polypeptide of the present invention, preferably to the polypeptide set forth in the Sequence Listing.

[0063] It will be appreciated that in any such kit, (a), (b), (c) or (d) may comprise a substantial component. Such a kit will be of use in diagnosing a disease or susceptibility to a disease, particularly diseases of the invention, amongst others.

[0064] The polynucleotide sequences of the present invention are valuable for chromosome localisation studies. The sequences set forth in the Sequence Listing are specifically targeted to, and can hybridize with, a particular location on an individual human chromosome. The mapping of relevant sequences to chromosomes according to the present invention is an important first step in correlating those sequences with gene associated disease. 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 in, for example, V. McKusick, Mendelian Inheritance in Man (available on-line through Johns Hopkins University Welch Medical Library). The relationship between genes and diseases that have been mapped to the same chromosomal region are then identified through linkage analysis (co-inheritance of physically adjacent genes). Precise human chromosomal localisations for a genomic sequence (gene fragment etc.) can be determined using Radiation Hybrid (RH) Mapping (Walter, M. Spillett, D., Thomas, P., Weissenbach, J., and Goodfellow, P., (1994) A method for constructing radiation hybrid maps of whole genomes, Nature Genetics 7, 22-28). A number of RH panels are available from Research Genetics (Huntsville, Ala., USA) e.g. the GeneBridge4 RH panel (Hum Mol Genet 1996 March;5(3):339-46 A radiation hybrid map of the human genome. Gyapay G, Schnmitt K, Fizames C, Jones H, Vega-Czarny N, Spillett D, Muselet D, Prud'Homme J F, Dib C, Auffray C, Morissette J, Weissenbach J, Goodfellow P N). To determine the chromosomal location of a gene using this panel, 93 PCRs are performed using primers designed from the gene of interest on RH DNAs. Each of these DNAs contains random human genomic fragments maintained in a hamster background (human/hamster hybrid cell lines). These PCRs result in 93 scores indicating the presence or absence of the PCR product of the gene of interest. These scores are compared with scores created using PCR products from genomic sequences of known location. This comparison is conducted at http://www.genome.wi.mit.edu/.

[0065] The polynucleotide sequences of the present invention are also valuable tools for tissue expression studies. Such studies allow the determination of expression patterns of polynucleotides of the present invention which may give an indication as to the expression patterns of the encoded polypeptides in tissues, by detecting the mRNAs that encode them. The techniques used are well known in the art and include in situ hydridization techniques to clones arrayed on a grid, such as cDNA microarray hybridization (Schena et al, Science, 270, 467-470, 1995 and Shalon et al, Genome Res, 6, 639-645, 1996) and nucleotide amplification techniques such as PCR. A preferred method uses the TAQMAN (Trade mark) technology available from Perkin Elmer. Results from these studies can provide an indication of the normal function of the polypeptide in the organism. In addition, comparative studies of the normal expression pattern of mRNAs with that of mRNAs encoded by an alternative form of the same gene (for example, one having an alteration in polypeptide coding potential or a regulatory mutation) can provide valuable insights into the role of the polypeptides of the present invention, or that of inappropriate expression thereof in disease. Such inappropriate expression may be of a temporal, spatial or simply quantitative nature.

[0066] A further aspect of the present invention relates to antibodies. The polypeptides of the invention or their fragments, or cells expressing them, can be used as immunogens to produce antibodies that are immunospecific for polypeptides of the present invention. The term “immunospecific” means that the antibodies have substantially greater affinity for the polypeptides of the invention than their affinity for other related polypeptides in the prior art.

[0067] Antibodies generated against polypeptides of the present invention may be obtained by administering the polypeptides or epitope-bearing fragments, or cells to an animal, preferably a non-human animal, using routine protocols. For preparation of monoclonal antibodies, any technique which provides antibodies produced by continuous cell line cultures can be used. Examples include the hybridoma technique (Kohler, G. and Milstein, C., Nature (1975) 256:495-497), the trioma technique, the human B-cell hybridoma technique (Kozbor et al., Immunology Today (1983) 4:72) and the EBV-hybridoma technique (Cole et al., Monoclonal Antibodies and Cancer Therapy, 77-96, Alan R. Liss, Inc., 1985).

[0068] Techniques for the production of single chain antibodies, such as those described in U.S. Pat. No. 4,946,778, can also be adapted to produce single chain antibodies to polypeptides of this invention. Also, transgenic mice, or other organisms, including other mammals, may be used to express humanized antibodies.

[0069] The above-described antibodies may be employed to isolate or to identify clones expressing the polypeptide or to purify the polypeptides by affinity chromatography. Antibodies against polypeptides of the present invention may also be employed to treat diseases of the invention, amongst others.

[0070] Polypeptides and polynucleotides of the present invention may also be used as vaccines. Accordingly, in a further aspect, the present invention relates to a method for inducing an immunological response in a mammal that comprises inoculating the mammal with a polypeptide of the present invention, adequate to produce antibody and/or T cell immune response, including, for example, cytokine-producing T cells or cytotoxic T cells, to protect said animal from disease, whether that disease is already established within the individual or not. An immunological response in a mammal may also be induced by a method comprises delivering a polypeptide of the present invention via a vector directing expression of the polynucleotide and coding for the polypeptide in vivo in order to induce such an immunological response to produce antibody to protect said animal from diseases of the invention. One way of administering the vector is by accelerating it into the desired cells as a coating on particles or otherwise. Such nucleic acid vector may comprise DNA, RNA, a modified nucleic acid, or a DNA/RNA hybrid. For use a vaccine, a polypeptide or a nucleic acid vector will be normally provided as a vaccine formulation (composition). The formulation may further comprise a suitable carrier. Since a polypeptide may be broken down in the stomach, it is preferably administered parenterally (for instance, subcutaneous, intramuscular, intravenous, or intra-dermal injection). Formulations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions that may contain anti-oxidants, buffers, bacteriostats and solutes that render the formulation instonic with the blood of the recipient; and aqueous and non-aqueous sterile suspensions that may include suspending agents or thickening agents. The formulations may be presented in unit-dose or multi-dose containers, for example, sealed ampoules and vials and may be stored in a freeze-dried condition requiring only the addition of the sterile liquid carrier immediately prior to use. The vaccine formulation may also include adjuvant systems for enhancing the immunogenicity of the formulation, such as oil-in water systems and other systems known in the art. The dosage will depend on the specific activity of the vaccine and can be readily determined by routine experimentation.

[0071] Polypeptides of the present invention have one or more biological functions that are of relevance in one or more disease states, in particular the diseases of the invention hereinbefore mentioned. It is therefore useful to identify compounds that stimulate or inhibit the function or level of the polypeptide. Accordingly, in a further aspect, the present invention provides for a method of screening compounds to identify those that stimulate or inhibit the function or level of the polypeptide. Such methods identify agonists or antagonists that may be employed for therapeutic and prophylactic purposes for such diseases of the invention as hereinbefore mentioned. Compounds may be identified from a variety of sources, for example, cells, cell-free preparations, chemical libraries, collections of chemical compounds, and natural product mixtures. Such agonists or antagonists so-identified may be natural or modified substrates, ligands, receptors, enzymes, etc., as the case may be, of the polypeptide; a structural or functional mimetic thereof (see Coligan et al., Current Protocols in Immunology 1(2):Chapter 5 (1991)) or a small molecule. Such small molecules preferably have a molecular weight below 2,000 daltons, more preferably between 300 and 1,000 daltons, and most preferably between 400 and 700 daltons. It is preferred that these small molecules are organic molecules.

[0072] The screening method may simply measure the binding of a candidate compound to the polypeptide, or to cells or membranes bearing the polypeptide, or a fusion protein thereof, by means of a label directly or indirectly associated with the candidate compound. Alternatively, the screening method may involve measuring or detecting (qualitatively or quantitatively) the competitive binding of a candidate compound to the polypeptide against a labeled competitor (e.g. agonist or antagonist). Further, these screening methods may test whether the candidate compound results in a signal generated by activation or inhibition of the polypeptide, using detection systems appropriate to the cells bearing the polypeptide. Inhibitors of activation are generally assayed in the presence of a known agonist and the effect on activation by the agonist by the presence of the candidate compound is observed. Further, the screening methods may simply comprise the steps of mixing a candidate compound with a solution containing a polypeptide of the present invention, to form a mixture, measuring an activity of the genes set forth in Table I in the mixture, and comparing activity of the mixture of the genes set forth in Table I to a control mixture which contains no candidate compound.

[0073] Polypeptides of the present invention may be employed in conventional low capacity screening methods and also in high-throughput screening (HTS) formats. Such HTS formats include not only the well-established use of 96- and, more recently, 384-well micotiter plates but also emerging methods such as the nanowell method described by Schullek et al, Anal Biochem., 246, 20-29, (1997).

[0074] Fusion proteins, such as those made from Fc portion and polypeptide of the genes set forth in Table I, as hereinbefore described, can also be used for high-throughput screening assays to identify antagonists for the polypeptide of the present invention (see D. Bennett et al., J Mol Recognition, 8:52-58 (1995); and K. Johanson et al., J Biol Chem, 270(16):9459-9471 (1995)).

[0075] The polynucleotides, polypeptides and antibodies to the polypeptide of the present invention may also be used to configure screening methods for detecting the effect of added compounds on the production of mRNA and polypeptide in cells. For example, an ELISA assay may be constructed for measuring secreted or cell associated levels of polypeptide using monoclonal and polyclonal antibodies by standard methods known in the art. This can be used to discover agents that may inhibit or enhance the production of polypeptide (also called antagonist or agonist, respectively) from suitably manipulated cells or tissues.

[0076] A polypeptide of the present invention may be used to identify membrane bound or soluble receptors, if any, through standard receptor binding techniques known in the art. These include, but are not limited to, ligand binding and crosslinking assays in which the polypeptide is labeled with a radioactive isotope (for instance, 125I), chemically modified (for instance, biotinylated), or fused to a peptide sequence suitable for detection or purification, and incubated with a source of the putative receptor (cells, cell membranes, cell supernatants, tissue extracts, bodily fluids). Other methods include biophysical techniques such as surface plasmon resonance and spectroscopy. These screening methods may also be used to identify agonists and antagonists of the polypeptide that compete with the binding of the polypeptide to its receptors, if any. Standard methods for conducting such assays are well understood in the art.

[0077] Examples of antagonists of polypeptides of the present invention include antibodies or, in some cases, oligonucleotides or proteins that are closely related to the ligands, substrates, receptors, enzymes, etc., as the case may be, of the polypeptide, e.g., a fragment of the ligands, substrates, receptors, enzymes, etc.; or a small molecule that bind to the polypeptide of the present invention but do not elicit a response, so that the activity of the polypeptide is prevented.

[0078] Screening methods may also involve the use of transgenic technology and the genes set forth in Table I. The art of constructing transgenic animals is well established. For example, the genes set forth in Table I may be introduced through microinjection into the male pronucleus of fertilized oocytes, retroviral transfer into pre- or post-implantation embryos, or injection of genetically modified, such as by electroporation, embryonic stem cells into host blastocysts. Particularly useful transgenic animals are so-called “knock-in” animals in which an animal gene is replaced by the human equivalent within the genome of that animal. Knock-in transgenic animals are useful in the drug discovery process, for target validation, where the compound is specific for the human target. Other useful transgenic animals are so-called “knock-out” animals in which the expression of the animal ortholog of a polypeptide of the present invention and encoded by an endogenous DNA sequence in a cell is partially or completely annulled. The gene knock-out may be targeted to specific cells or tissues, may occur only in certain cells or tissues as a consequence of the limitations of the technology, or may occur in all, or substantially all, cells in the animal. Transgenic animal technology also offers a whole animal expression-cloning system in which introduced genes are expressed to give large amounts of polypeptides of the present invention.

[0079] Screening kits for use in the above described methods form a further aspect of the present invention. Such screening kits comprise:

[0080] (a) a polypeptide of the present invention;

[0081] (b) a recombinant cell expressing a polypeptide of the present invention;

[0082] (c) a cell membrane expressing a polypeptide of the present invention; or

[0083] (d) an antibody to a polypeptide of the present invention;

[0084] which polypeptide is preferably that set forth in the Sequence Listing.

[0085] It will be appreciated that in any such kit, (a), (b), (c) or (d) may comprise a substantial component.

[0086] Glossary

[0087] The following definitions are provided to facilitate understanding of certain terms used frequently hereinbefore.

[0088] “Antibodies” as used herein includes polyclonal and monoclonal antibodies, chimeric, single chain, and humanized antibodies, as well as Fab fragments, including the products of an

[0089] Fab or other immunoglobulin expression library.

[0090] “Isolated” means altered “by the hand of man” from its natural state, i.e., if it occurs in nature, it has been changed or removed from its original environment, or both. For example, a polynucleotide or a polypeptide naturally present in a living organism is not “isolated,” but the same polynucleotide or polypeptide separated from the coexisting materials of its natural state is “isolated”, as the term is employed herein. Moreover, a polynucleotide or polypeptide that is introduced into an organism by transformation, genetic manipulation or by any other recombinant method is “isolated” even if it is still present in said organism, which organism may be living or non-living.

[0091] “Secreted protein activity or secreted polypeptide activity” or “biological activity of the secreted protein or secreted polypeptide” refers to the metabolic or physiologic function of said secreted protein including similar activities or improved activities or these activities with decreased undesirable side-effects. Also included are antigenic and immunogenic activities of said secreted protein.

[0092] “Secreted protein gene” refers to a polynucleotide comprising any of the attached nucleotide sequences or allelic variants thereof and/or their complements.

[0093] “Polynucleotide” generally refers to any polyribonucleotide (RNA) or polydeoxribonucleotide (DNA), which may be unmodified or modified RNA or DNA. “Polynucleotides” include, without limitation, single- and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is mixture of single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single- and double-stranded regions. In addition, “polynucleotide” refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA. The term “polynucleotide” also includes DNAs or RNAs containing one or more modified bases and DNAs or RNAs with backbones modified for stability or for other reasons. “Modified” bases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications may be made to DNA and RNA; thus, “polynucleotide” embraces chemically, enzymatically or metabolically modified forms of polynucleotides as typically found in nature, as well as the chemical forms of DNA and RNA characteristic of viruses and cells. “Polynucleotide” also embraces relatively short polynucleotides, often referred to as oligonucleotides.

[0094] “Polypeptide” refers to any polypeptide comprising two or more amino acids joined to each other by peptide bonds or modified peptide bonds, i.e., peptide isosteres. “Polypeptide” refers to both short chains, commonly referred to as peptides, oligopeptides or oligomers, and to longer chains, generally referred to as proteins. Polypeptides may contain amino acids other than the 20 gene-encoded amino acids. “Polypeptides” include amino acid sequences modified either by natural processes, such as post-translational processing, or by chemical modification techniques that are well known in the art. Such modifications are well described in basic texts and in more detailed monographs, as well as in a voluminous research literature. Modifications may occur anywhere in a polypeptide, including the peptide backbone, the amino acid side-chains and the amino or carboxyl termini. It will be appreciated that the same type of modification may be present to the same or varying degrees at several sites in a given polypeptide. Also, a given polypeptide may contain many types of modifications. Polypeptides may be branched as a result of ubiquitination, and they may be cyclic, with or without branching. Cyclic, branched and branched cyclic polypeptides may result from post-translation natural processes or may be made by synthetic methods. Modifications include acetylation, acylation, ADP-ribosylation, amidation, biotinylation, covalent attachment of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphotidylinositol, cross-linking, cyclization, disulfide bond formation, demethylation, formation of covalent cross-links, formation of cystine, formation of pyroglutamate, formylation, gamma-carboxylation, glycosylation, GPI anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, sulfation, transfer-RNA mediated addition of amino acids to proteins such as arginylation, and ubiquitination (see, for instance, Proteins—Structure and Molecular Properties, 2nd Ed., T. E. Creighton, W. H. Freeman and Company, New York, 1993; Wold, F., Post-translational Protein Modifications: Perspectives and Prospects, 1-12, in Post-translational Covalent Modification of Proteins, B. C. Johnson, Ed., Academic Press, New York, 1983; Seifter et al., “Analysis for protein modifications and nonprotein cofactors”, Meth Enzymol, 182, 626-646, 1990, and Rattan et al., “Protein Synthesis: Post-translational Modifications and Aging”, Ann NY Acad Sci, 663, 48-62, 1992).

[0095] “Fragment” of a polypeptide sequence refers to a polypeptide sequence that is shorter than the reference sequence but that retains essentially the same biological function or activity as the reference polypeptide. “Fragment” of a polynucleotide sequence refers to a polynucleotide sequence that is shorter than the reference sequence set forth in the Sequence Listing.

[0096] “Variant” refers to a polynucleotide or polypeptide that differs from a reference polynucleotide or polypeptide, but retains the essential properties thereof. A typical variant of a polynucleotide differs in nucleotide sequence from the reference polynucleotide. Changes in the nucleotide sequence of the variant may or may not alter the amino acid sequence of a polypeptide encoded by the reference polynucleotide. Nucleotide changes may result in amino acid substitutions, additions, deletions, fusions and truncations in the polypeptide encoded by the reference sequence, as discussed below. A typical variant of a polypeptide differs in amino acid sequence from the reference polypeptide. Generally, alterations are limited so that the sequences of the reference polypeptide and the variant are closely similar overall and, in many regions, identical. A variant and reference polypeptide may differ in amino acid sequence by one or more substitutions, insertions, deletions in any combination. A substituted or inserted amino acid residue may or may not be one encoded by the genetic code. Typical conservative substitutions include Gly, Ala; Val, Ile, Leu; Asp, Glu; Asn, Gln; Ser, Thr; Lys, Arg; and Phe and Tyr. A variant of a polynucleotide or polypeptide may be naturally occurring such as an allele, or it may be a variant that is not known to occur naturally. Non-naturally occurring variants of polynucleotides and polypeptides may be made by mutagenesis techniques or by direct synthesis. Also included as variants are polypeptides having one or more post-translational modifications, for instance glycosylation, phosphorylation, methylation, ADP ribosylation and the like. Embodiments include methylation of the N-terminal amino acid, phosphorylations of serines and threonines and modification of C-terminal glycines.

[0097] “Allele” refers to one of two or more alternative forms of a gene occurring at a given locus in the genome.

[0098] “Polymorphism” refers to a variation in nucleotide sequence (and encoded polypeptide sequence, if relevant) at a given position in the genome within a population.

[0099] “Single Nucleotide Polymorphism” (SNP) refers to the occurrence of nucleotide variability at a single nucleotide position in the genome, within a population. An SNP may occur within a gene or within intergenic regions of the genome. SNPs can be assayed using Allele Specific Amplification (ASA). For the process at least 3 primers are required. A common primer is used in reverse complement to the polymorphism being assayed. This common primer can be between 50 and 1500 bps from the polymorphic base. The other two (or more) primers are identical to each other except that the final 3′ base wobbles to match one of the two (or more) alleles that make up the polymorphism. Two (or more) PCR reactions are then conducted on sample DNA, each using the common primer and one of the Allele Specific Primers.

[0100] “Splice Variant” as used herein refers to cDNA molecules produced from RNA molecules initially transcribed from the same genomic DNA sequence but which have undergone alternative RNA splicing. Alternative RNA splicing occurs when a primary RNA transcript undergoes splicing, generally for the removal of introns, which results in the production of more than one mRNA molecule each of that may encode different amino acid sequences. The term splice variant also refers to the proteins encoded by the above cDNA molecules.

[0101] “Identity” reflects a relationship between two or more polypeptide sequences or two or more polynucleotide sequences, determined by comparing the sequences. In general, identity refers to an exact nucleotide to nucleotide or amino acid to amino acid correspondence of the two polynucleotide or two polypeptide sequences, respectively, over the length of the sequences being compared.

[0102] “% Identity”—For sequences where there is not an exact correspondence, a “% identity” may be determined. In general, the two sequences to be compared are aligned to give a maximum correlation between the sequences. This may include inserting “gaps” in either one or both sequences, to enhance the degree of alignment. A % identity may be determined over the whole length of each of the sequences being compared (so-called global alignment), that is particularly suitable for sequences of the same or very similar length, or over shorter, defined lengths (so-called local alignment), that is more suitable for sequences of unequal length.

[0103] “Similarity” is a further, more sophisticated measure of the relationship between two polypeptide sequences. In general, “similarity” means a comparison between the amino acids of two polypeptide chains, on a residue by residue basis, taking into account not only exact correspondences between a between pairs of residues, one from each of the sequences being compared (as for identity) but also, where there is not an exact correspondence, whether, on an evolutionary basis, one residue is a likely substitute for the other. This likelihood has an associated “score” from which the “% similarity” of the two sequences can then be determined.

[0104] Methods for comparing the identity and similarity of two or more sequences are well known in the art. Thus for instance, programs available in the Wisconsin Sequence Analysis Package, version 9.1 (Devereux J et al, Nucleic Acids Res, 12, 387-395, 1984, available from Genetics Computer Group, Madison, Wis., USA), for example the programs BESTFIT and GAP, may be used to determine the % identity between two polynucleotides and the % identity and the % similarity between two polypeptide sequences. BESTFIT uses the “local homology” algorithm of Smith and Waterman (J Mol Biol, 147,195-197, 1981, Advances in Applied Mathematics, 2, 482-489, 1981) and finds the best single region of similarity between two sequences. BESTFIT is more suited to comparing two polynucleotide or two polypeptide sequences that are dissimilar in length, the program assuming that the shorter sequence represents a portion of the longer. In comparison, GAP aligns two sequences, finding a “maximum similarity”, according to the algorithm of Neddleman and Wunsch (J Mol Biol, 48, 443-453, 1970). GAP is more suited to comparing sequences that are approximately the same length and an alignment is expected over the entire length. Preferably, the parameters “Gap Weight” and “Length Weight” used in each program are 50 and 3, for polynucleotide sequences and 12 and 4 for polypeptide sequences, respectively. Preferably, % identities and similarities are determined when the two sequences being compared are optimally aligned.

[0105] Other programs for determining identity and/or similarity between sequences are also known in the art, for instance the BLAST family of programs (Altschul S F et al, J Mol Biol, 215, 403-410, 1990, Altschul S F et al, Nucleic Acids Res., 25:389-3402, 1997, available from the National Center for Biotechnology Information (NCBI), Bethesda, Md., USA and accessible through the home page of the NCBI at www.ncbi.nlm.nih.gov) and FASTA (Pearson W R, Methods in Enzymology, 183, 63-99, 1990; Pearson W R and Lipman D J, Proc Nat Acad Sci USA, 85, 2444-2448,1988, available as part of the Wisconsin Sequence Analysis Package).

[0106] Preferably, the BLOSUM62 amino acid substitution matrix (Henikoff S and Henikoff J G, Proc. Nat. Acad Sci. USA, 89, 10915-10919, 1992) is used in polypeptide sequence comparisons including where nucleotide sequences are first translated into amino acid sequences before comparison.

[0107] Preferably, the program BESTFIT is used to determine the % identity of a query polynucleotide or a polypeptide sequence with respect to a reference polynucleotide or a polypeptide sequence, the query and the reference sequence being optimally aligned and the parameters of the program set at the default value, as hereinbefore described.

[0108] “Identity Index” is a measure of sequence relatedness which may be used to compare a candidate sequence (polynucleotide or polypeptide) and a reference sequence. Thus, for instance, a candidate polynucleotide sequence having, for example, an Identity Index of 0.95 compared to a reference polynucleotide sequence is identical to the reference sequence except that the candidate polynucleotide sequence may include on average up to five differences per each 100 nucleotides of the reference sequence. Such differences are selected from the group consisting of at least one nucleotide deletion, substitution, including transition and transversion, or insertion. These differences may occur at the 5′ or 3′ terminal positions of the reference polynucleotide sequence or anywhere between these terminal positions, interspersed either individually among the nucleotides in the reference sequence or in one or more contiguous groups within the reference sequence. In other words, to obtain a polynucleotide sequence having an Identity Index of 0.95 compared to a reference polynucleotide sequence, an average of up to 5 in every 100 of the nucleotides of the in the reference sequence may be deleted, substituted or inserted, or any combination thereof, as hereinbefore described. The same applies mutatis mutatidis for other values of the Identity Index, for instance 0.96, 0.97, 0.98 and 0.99.

[0109] Similarly, for a polypeptide, a candidate polypeptide sequence having, for example, an Identity Index of 0.95 compared to a reference polypeptide sequence is identical to the reference sequence except that the polypeptide sequence may include an average of up to five differences per each 100 amino acids of the reference sequence. Such differences are selected from the group consisting of at least one amino acid deletion, substitution, including conservative and non-conservative substitution, or insertion. These differences may occur at the amino- or carboxy-terminal positions of the reference polypeptide sequence or anywhere between these terminal positions, interspersed either individually among the amino acids in the reference sequence or in one or more contiguous groups within the reference sequence. In other words, to obtain a polypeptide sequence having an Identity Index of 0.95 compared to a reference polypeptide sequence, an average of up to 5 in every 100 of the amino acids in the reference sequence may be deleted, substituted or inserted, or any combination thereof, as hereinbefore described. The same applies mutatis mutatidis for other values of the Identity Index, for instance 0.96, 0.97, 0.98 and 0.99.

[0110] The relationship between the number of nucleotide or amino acid differences and the Identity Index may be expressed in the following equation:

n a ≦x a −(xa•I),

[0111] in which:

[0112] na is the number of nucleotide or amino acid differences,

[0113] xa is the total number of nucleotides or amino acids in a sequence set forth in the Sequence Listing,

[0114] I is the Identity Index,

[0115] • is the symbol for the multiplication operator, and

[0116] in which any non-integer product of xa and I is rounded down to the nearest integer prior to subtracting it from xa.

[0117] “Homolog” is a generic term used in the art to indicate a polynucleotide or polypeptide sequence possessing a high degree of sequence relatedness to a reference sequence. Such relatedness may be quantified by determining the degree of identity and/or similarity between the two sequences as hereinbefore defined. Falling within this generic term are the terms “ortholog”, and “paralog”. “Ortholog” refers to a polynucleotide or polypeptide that is the functional equivalent of the polynucleotide or polypeptide in another species. “Paralog” refers to a polynucleotide or polypeptide that within the same species which is functionally similar.

[0118] “Fusion protein” refers to a protein encoded by two, often unrelated, fused genes or fragments thereof. In one example, EP-A-0 464 533-A discloses fusion proteins comprising various portions of constant region of immunoglobulin molecules together with another human protein or part thereof. In many cases, employing an immunoglobulin Fc region as a part of a fusion protein is advantageous for use in therapy and diagnosis resulting in, for example, improved pharmacokinetic properties [see, e.g., EP-A 0232 262]. On the other hand, for some uses it would be desirable to be able to delete the Fc part after the fusion protein has been expressed, detected and purified.

[0119] All publications and references, including but not limited to patents and patent applications, cited in this specification are herein incorporated by reference in their entirety as if each individual publication or reference were specifically and individually indicated to be incorporated by reference herein as being fully set forth. Any patent application to which this application claims priority is also incorporated by reference herein in its entirety in the manner described above for publications and references.

TABLE I
			Corresponding
	GSK	Nucleic Acid	Protein
Gene Name	Gene ID	SEQ ID NO's	SEQ ID NO's
sbg237163LIPASE	237163	SEQ ID NO: 1	SEQ ID NO: 23
sbg251170CEAa	251170	SEQ ID NO: 2	SEQ ID NO: 24
		SEQ ID NO: 3	SEQ ID NO: 25
sbg389686WNT15a	389686	SEQ ID NO: 4	SEQ ID NO: 26
		SEQ ID NO: 5	SEQ ID NO: 27
sbg236015LIPASE	236015	SEQ ID NO: 6	SEQ ID NO: 28
		SEQ ID NO: 7	SEQ ID NO: 29
sbg417005	417005	SEQ ID NO: 8	SEQ ID NO: 30
LAMININ_ALPHA		SEQ ID NO: 9	SEQ ID NO: 31
sbg425649KINASEa	425649	SEQ ID NO: 10	SEQ ID NO: 32
sbg419582	419582	SEQ ID NO: 11	SEQ ID NO: 33
PROTOCADHERIN		SEQ ID NO: 12	SEQ ID NO: 34
sbg453915	453915	SEQ ID NO: 13	SEQ ID NO: 35
TECTORINa
SBh385630.antiinflam	385630	SEQ ID NO: 14	SEQ ID NO: 36
		SEQ ID NO: 15	SEQ ID NO: 37
sbg471005nAChR	471005	SEQ ID NO: 16	SEQ ID NO: 38
sbg442445PROa	442445	SEQ ID NO: 17	SEQ ID NO: 39
sbg456548CytoRa	456548	SEQ ID NO: 18	SEQ ID NO: 40
		SEQ ID NO: 19	SEQ ID NO: 41
sbg456548CytoRa	456548b	SEQ ID NO: 20	SEQ ID NO: 42
sbg442358PROa	442358	SEQ ID NO: 21	SEQ ID NO: 43
		SEQ ID NO: 22	SEQ ID NO: 44

[0120]

TABLE II
				Cell
				Localization
	Gene	Closest Polynuclotide	Closest Polypeptide by	(by
Gene Name	Family	by homology	homology	homology)
sbg237163	Pancreatic	GB: AC011328	Mouse pancreatic lipase	Secreted
LIPASE	lipase	Direct submitted (OCT-	related protein 1, gi:
		06-1999) Genome	9256628
		Therapeutics	Remington, S. G.,
		Corporation, 100	Lima, P. H. and Nelson, J. D.
		Beaver Street,	Invest. Ophthalmol. Vis.
		Waltham, MA 02453,	Sci. 40 (6), 1081-1090
		USA	(1999)
sbg251170CEAa	Carcinoem	GB: AC020914	Mouse putative protein,	Secreted
	bryonic	Submitted (JAN-12-	gi: 12842545
	antigen	2000) Production	Carninci, P., Shibata, Y.,
		Sequencing Facility,	Hayatsu, N., Sugahara, Y.,
		DOE Joint	Shibata, K., Itoh, M.,
		Genome Institute, 2800	Konno, H., Okazaki, Y.,
		Mitchell Drive, Walnut	Muramatsu, M. and
		Creek, CA 94598, USA	Hayashizaki, Y.
			Genome Res. 10 (10),
			1617-1630 (2000).
sbg389686	WNT15	GB: AC015855	Chicken WNT14 protein,	Secreted
WNT15a		Directly submitted (NOV-	gi: 3915306
		17-1999) Whitehead	Bergstein I, Eisenberg L M,
		Institute/MIT Center	Bhalerao J, Jenkins N A,
		for Genome Research,	Copeland N G, Osborne
		320 Charles Street,	M P, Bowcock A M, Brown
		Cambridge, MA 02141,	A M; 1997; Genomics
		USA.	46: 450-8.
sbg236015LIPASE	Lysosomal	GB: AL358532	Rat lingual lipase,	Secreted
	acid	Directly submitted (DEC-	gi: 126307
	lipase	15-2000) by Sanger	Docherty, A. J.,
		Centre, Hinxton,	Bodmer, M. W., Angal, S.,
		Cambridgeshire, CB 10	Verger, R., Riviere, C.,
		1SA, UK.	Lowe, P. A., Lyons, A.,
			Emtage, J. S. and Harris, T. J.
			Nucleic Acids Res. 13 (6),
			1891-1903 (1985)
sbg417005LAMININ—	Laminin	GB: AL354836	Human laminin alpha 5,	Secreted
ALPHA	alpha	Direct submitted (MAY-	gi: 12274842
		02-2000) Sanger	Submitted (FEB-14-2001)
		Centre, Hinxton,	by Sanger Centre, Hinxton,
		Cambridgeshire, CB 10	Cambridgeshire, CB 10
		1SA	1SA, UK.
sbg425649KINASEa	Casein	GB: AL356107	Human casein kinase I-	Cytosolic
	kinase I-	Submitted (MAY-16-	alpha,
	alpha	2000) by	gi: 2134872
		Sanger Centre,	Fish, K. J.,
		Hinxton,	Cegielska, A.,
		Cambridgeshire, CB 10	Getman, M. E.,
		1SA, UK.	Landes, G. M. and
			Virshup, D. M.
			J. Biol. Chem. 270 (25),
			14875-14883 (1995)
sbg419582PROTOCADHERIN	Protocadherin	GB: AL355593	Human protocadherin 68	Secreted
		Direct submitted (MAY-	gi: 11433373
		17-2000) Sanger	Submitted (NOV-16-2000)
		Centre, Hinxton,	by National Center for
		Cambridgeshire, CB 10	Biotechnology
		1SA, UK.	Information, NIH,
			Bethesda, MD 20894, USA
sbg453915TECTORINa	Tectorin	SC: AL157786	Mouse tectorin beta,	Secreted
	Beta	Submitted (MAY-04-	gi: 7363457
		2001) by Sanger	Legan, P. K., Rau, A.,
		Centre, Hinxton,	Keen, J. N. and
		Cambridgeshire, CB 10	Richardson, G. P.
		1SA, UK.	J. Biol. Chem. 272 (13),
			8791-8801 (1997)
SBh385630.	Lipase	GB: AC015525	Rabbit lacrimal lipase,	Secreted
antiinflam		Submitted (NOV-16-	gi: 13560884
		1999) by Whitehead	Submitted (FEB-20-2001)
		Institute/MIT Center	Ophthalmology, Regions
		for Genome Research,	Hospital, 640 Jackson
		320 Charles Street,	Street, St. Paul, MN 55101,
		Cambridge, MA 02141,	USA
		USA
sbg471005nAChR	Nicotinic	GB: AC060812	Human cholinergic	Membrane-
	acetylcholine	Direct submitted	receptor, nicotinic, alpha	bound
	receptor	(APR-20-2000)	polypeptide 10,
		Whitehead	gi: 11138123
		Institute/MIT	Lustig, L. R., Peng, H.,
		Center for	Hiel, H., Yamamoto, T.
		Genome	and Fuchs, P. A.
		Research, 320	Genomics 73 (3), 272-
		Charles Street,	283 (2001)
		Cambridge, MA
		02141, USA
sbg442445PROa	Leucine rich	GB: AC060234	RIKEN cDNA mouse	Cytosolic
	repeat protein	Submitted	4930442L21 gene
		(APR-20-2000)	Carninci, P., Shibata, Y.,
		Genome	Hayatsu, N.,
		Therapeutics	Sugahara, Y., Shibata, K.,
		Corporation, 100	Itoh, M., Konno, H.,
		Beaver Street,	Okazaki, Y.,
		Waltham,	Muramatsu, M. and
		MA 02453, USA	Hayashizaki, Y.
			Genome Res. 10 (10),
			1617-1630 (2000)
sbg456548CytoRa	Cytokine	GB: AL158138	Human IL20 receptor,	Membrane-
	receptor	Submitted (JAN-	gi: 7657691	bound
		20-2001) by	Xie M H, Aggarwal S,
		Sanger Centre,	Ho W H, Foster J, Zhang
		Hinxton,	Z, Stinson J, Wood W I,
		Cambridgeshire,	Goddard AD and Gurney
		CB 10 1SA, UK.	A L.
			J. Biol. Chem. 275 (40),
			31335-31339 (2000)
sbg442358PROa	Leucine rich	GB: AL139099	Human EXMAD-9	Membrane-
	repeat protein	Submitted (MAY-	geneseqp: AAB27231	bound
		23-2000) by	Submitted by INCYTE
		Genoscope-	GENOMICS INC
		Centre National	Application and
		de Sequencage:	publication date:
		BP 191 91006	WO200068380-A2, NOV-
		EVRY cedex —	16-00
		FRANCE

[0121]

TABLE III
		Associated
Gene Name	Uses	Diseases
sbg237163	An embodiment of the invention is the use of sbg237163	Cancer, infection,
LIPASE	LIPASE as replacement enzymes for patients with chronic	autoimmune
	pancreatitis. A close homologue of sbg237163 LIPASE	disorder,
	is pancreatic lipase. Pancreatic lipase hydrolyzes dietary	hematopoietic
	long chain triacylglycerol to free fatty acids and	disorder, wound
	monoacylglycerols in the intestinal lumen (Lowe M E,	healing disorders,
	Rosenblum J L, and Strauss A W; 1989; J Biol Chem	inflammation.
	264: 20042-8). Pancreatic steatorrhea and pancreatic
	diabetes are the dominant symptoms of patients in a
	certain stage of chronic pancreatitis. In this stage, the
	nutritional state is greatly disturbed and hypoglycemia and
	labile infection are involved. Pancreatic enzyme
	replacement therapy is the principal treatment method for
	pancreatic steatorrhea (Nakamura T, Takeuchi T, and
	Tando Y; 1998; Pancreas 16: 329-36.
sbg251170CEAa	An embodiment of the invention is the use of	Cancer,
	sbg251170CEAa as cell-surface molecules mediating	autoimmune
	cell-specific interactions in normal and neoplastic cells. A	disorders, wound
	close homologue of sbg251170CEAa is	healing disorders,
	carcinoembryonic antigen-related cell adhesion molecule	hematopoietic
	6. Carcinoembryonic antigen-related cell adhesion	disorders and
	molecule 6 is claimed to function as a cell-surface	infection
	molecules mediating cell-specific interactions in normal
	and neoplastic cells (1. Barnett T, Goebel S J, Nothdurft
	M A, Elting J J, Carcinoembryonic antigen family:
	characterization of cDNAs coding for NCA and CEA and
	suggestion of nonrandom sequence variation in their
	conserved loop-domains. Genomics 1988 Jul; 3(1): 59-66.
	2. Inazawa J, Abe T, Inoue K, Misawa S, Oikawa S,
	Nakazato H, Yoshida M C. Regional assignment of
	nonspecific cross-reacting antigen (NCA) of the CEA
	gene family to chromosome 19 at band q13.2. Cytogenet
	Cell Genet 1989; 52(1-2): 28-31).
sbg389686	An embodiment of the invention is the use of	Cancer, infection,
WNT15a	sbg389686WNT15a in regulation of cell growth and	autoimmune
	differentiation. Close homologues of	disorder,
	sbg389686WNT15a are Wnt proteins. Wnt proteins are	hematopoietic
	involved in critical developmental processes in both	disorder, wound
	vertebrates and invertebrates and are implicated in	healing disorders,
	regulation of cell growth and differentiation in certain	and inflammation
	adult mammalian tissues (Bergstein I, Eisenberg L M,
	Bhalerao J, Jenkins N A, Copeland N G, Osborne M P,
	Bowcock A M, Brown A M; 1997; Genomics 46: 450-8).
	The Wnt gene family consists of at least 15 structurally
	related genes that encode secreted extracellular
	signaling factors. Wnt signaling is involved in many
	mammalian developmental processes, including cell
	proliferation, differentiation and epithelial-mesenchymal
	interactions, through which they contribute to the
	development of tissues and organs such as the limbs, the
	brain, the reproductive tract and the kidney. Evidence
	from tumor expression studies and transgenic animals
	experiments suggests that inappropriate activation of the
	Wnt signaling pathway is a major feature in human
	neoplasia and that oncogenic activation of this pathway
	can occur at many levels. Inappropriate expression of
	the Wnt ligand and Wnt binding proteins have been
	found in a variety of human tumors (Smalley M J, Dale
	T C; 1999; Cancer Metastasis Rev 18: 215-30).
sbg236015LIPASE	An embodiment of the invention is the use of	Cancer, infection,
	sbg236015LIPASE for treating lipase deficiency. A	autoimmune
	close homologue of sbg236015LIPASE is lysosomal	disorder,
	acid lipase. The lysosomal acid lipase catalyzes the	hematopoietic
	deacylation of triacylglyceryl and cholesteryl ester core	disorder, wound
	lipids of endocytosed low density lipoproteins. This	healing disorders,
	activity is deficient in patients with Wolman disease and	inflammation,
	cholesteryl ester storage disease, which are caused by a	Wolman disease,
	deficiency of lysosomal acid lipase activity, resulting in	and cholesteryl
	massive accumulation of cholesteryl ester and	ester storage
	triglycerides (Anderson R A, Sando G N; 1991; J Biol	disease
	Chem 266: 22479-84).
sbg417005LAMININ—	An embodiment of the invention is the use of	Cancer, infection,
ALPHA	sbg417005LAMININ_ALPHA to promote myogenesis	autoimmune
	in skeletal muscle, outgrowth of neurites from central	disorder,
	and peripheral neurons, and mesenchymal to epithelial	hematopoietic
	transitions in kidney. A close homologue of	disorder, wound
	sbg417005LAMININ_ALPHA is laminin. Laminins	healing disorders,
	trimers, composed of alpha, beta, and gamma chains, are	inflammation,
	components of all basal laminae (BLs) throughout the	congenital
	bodies. In mammals they play at least three essential	muscular
	roles. First, they are major structural elements of BLs,	dystrophy, and
	forming one of two self-assembling networks to which	junctional
	other glycoproteins and proteoglycans of the BL attach.	epidermolysis
	Second, they interact with cell surface components such	bullosa
	as dystroglycan to attach cells to the extracellular
	matrix. Third, they are signaling molecules that interact
	with cellular receptors such as the integrins to convey
	important information to the cell interior. The alpha
	chains are ligands for most cellular laminin receptors.
	(Miner J H, Patton B L, Lentz S I, Gilbert D J, Snider W D,
	Jenkins N A, Copeland N G, Sanes J R; 1997; J Cell Biol
	137: 685-701).
sbg425649KINASEa	An embodiment of the invention is the use of	Cancer, wound
	sbg425649KINASEa in DNA replication and repair,	healing disorders,
	membrane trafficking, neuroprotective, cytostatic,	autoimmune
	cardioactive, immunomodulatory, muscular, vulnerary,	disorders,
	gastrointestinal, nephrotropic, anti-infective,	hematopoietic
	gynaecological and antibacterial activities, and can be	disorders and
	used in gene therapy. Close homologues of	infection
	sbg425649KINASEa is mammalian casein kinases I
	(CKI) and human prostate cancer associated protein.
	CKI belongs to a family of serine/threonine protein
	kinases involved in diverse cellular processes including
	DNA replication and repair, membrane trafficking,
	circadian rhythms and Wnt signaling. Human prostate
	cancer associated proteins have neuroprotective,
	cytostatic, cardioactive, immunomodulatory, muscular,
	vulnerary, gastrointestinal, nephrotropic, anti-infective,
	gynaecological and antibacterial activities, and can be
	used in gene therapy.
sbg419582PROTOCADHERIN	An embodiment of the invention is the use of	Cancer, infection,
	sbg419582PROTOCADHERIN in functional systems of	autoimmune
	the nervous system, and may be involved in the	disorder,
	formation of the neural network. A close homologue of	hematopoietic
	sbg419582PROTOCADHERIN is protocadherin. The	disorder, wound
	expression of protocadherin is developmentally	healing disorders,
	regulated in a subset of the functional systems of the	inflammation,
	nervous system, and may be involved in the formation	Parkinson's
	of the neural network by segregation of the brain nuclei	disease,
	and mediation of the axonal connections (Hirano S, Yan	Huntington's
	Q, Suzuki S T; 1999; J Neurosci 19: 995-1005). The	chorea, and
	members of the cadherin superfamily are divided into	multiple sclerosis
	two groups: classical cadherin type and protocadherin
	type. The current cadherins appear to have evolved from
	protocadherin (Suzuki S T; 1996; J Cell Sci 109: 2609-11).
sbg453915TECTORINa	An embodiment of the invention is the use of	Infection, cancer,
	sbg453915TECTORINa, a secreted protein, in cellular	wound healing
	adhesion. A close homologue of	disorders,
	sbg453915TECTORINa is mouse tectorin beta. The	hemotopoietic
	beta-tectorin is a protein of 36,074 Da that contains 4	disorders and
	consensus N glycosylation sites and a single zona	autoimmune
	pellucida domain. It is similar to components of the	disorders.
	sperm-egg adhesion system, and, as such may have a
	similar functional role (Legan P K, Rau A, Keen J N,
	Richardson G P, The mouse tectorins. Modular matrix
	proteins of the inner ear homologous to components of
	the sperm-egg adhesion system. J Biol Chem 1997 Mar
	28; 272(13): 8791-801).
SBh385630.	An embodiment of the invention is the use of	Lematopoietic
antiinflam	SBh385630.antiinflam in gene therapy and are also	disorders, wound
	suggested to have cytokine and cell	healing disorders,
	proliferation/differentiation activity, immune	viral and bacterial
	stimulating (e.g. vaccines) or suppressing activity,	infections, cancer,
	haematopoiesis regulating activity, tissue growth	and autoimmune
	activity, activin/inhibinactivity,	diseases
	chemotactic/chemokinetic activity, haemostatic and
	thrombolytic activity, receptor/ligand activity, anti-
	inflammatory activity, cadherin/tumour invasion
	suppressor activity, and tumour inhibition activity.
	Lipases are also reported to be useful for gene therapy
	(WO9957132-A1; Agostino, M. J., filed by GENETICS
	INST INC.). Close homologues of
	SBh385630.antiinflam include lipases.
sbg471005n	An embodiment of the invention is the use of	Cancer, infection,
AChR	sbg471005nAChR in physiological and behavioural	autoimmune
	processes of the brain. A close homologue of	disorder,
	sbg471005nAChR is neuronal nicotinic acetylcholine	hematopoietic
	receptors. Neuronal nicotinic acetylcholine receptors	disorder, wound
	are a family of ion channels which are widely	healing disorders,
	distributed in the human brain. There are many	inflammation,
	subtypes, and each has individual pharmacological and	Alzheimer's
	functional profiles. They mediate the effects of nicotine,	disease,
	and are involved in a number of physiological and	Parkinson's
	behavioural processes. Additionally they may be	disease, and
	implicated in a number of pathological conditions such	schizophrenia
	as Alzheimer's disease, Parkinson's disease and
	schizophrenia (Paterson D, Nordberg A; 2000; Prog
	Neurobiol 61: 75-111).
sbg442445PROa	An embodiment of the invention is the use of	Inflammation,
	sbg442445PROa which may be involved in protein-	autoimmune
	protein interation and signal transduction in immune	disorders, asthma,
	system. sbg442445PROa was expressed predominantly	allergies
	in lung and spleen/lymph. It encodes a protein with	and
	leucine rich repeats which may be involved in protein-	sbg442445PROa-
	protein interation and signal transduction in immune	associated
	systems.	disorders
sbg456548CytoRa	The present gene has been cloned. Sybrman data	Chronic and acute
	showed its high expression levels in placenta and	inflammation,
	moderate levels in spleen and lymph. A close	allergy, arthritis
	homologue of sbg456548CytoRa is another Class II	(including
	cytokine receptor, ZCYTOR7. An embodiment of the	rheumatoid
	invention is the use of sbg456548CytoRa, a decoy	arthritis),
	receptor, in the identification of other ligands, the	septicemia,
	promotion of anti-microbial activation of these cells,	autoimmune
	and/or potentiate the effectiveness of the natural ligand.	diseases (e.g.,
	Growth factors are known to promote the progression of	inflammatory
	cancer. A decoy receptor could interfere with that	bowel disease,
	process. Proliferation, survival and differentiation can	psoriasis),
	be transduced from activated cytokine receptors (Cell	transplant
	Signal. 1998. 10(9): 619-628). Blocking these events	rejection, graft vs.
	could be crucial in modulating various diseases.	host disease,
	The decoy receptor could potentially interfere with	infection, stroke,
	binding of these or other putative ligands, preventing	ischemia, acute
	downstream effects (Blood. 1999. 94(6): 1943-1951).	respiratory disease
	GM-CSF also has anti-apoptotic activity. A decoy	syndrome, asthma,
	receptor might then be able to block GM-CSF's anti-	restenosis, brain
	apoptotic actions when appropriate (Mol Biol Cell.	injury, AIDS, bone
	1999. 10(11): 3959-3970). Roles for blocking the	diseases, cancer,
	activity of the decoy receptor can be envisioned. GM-	atheroschlerosis,
	CSF promotes anti-microbial functions of mature	Alzheimers
	neutrophils. Inhibiting the activity of an interfering	disease,,
	decoy receptor could promote anti-microbial activation	hematopoietic
	of these cells. Furthermore, rhGM-CSF is in wide	disorder, and
	clinical use to fight acute myeloid leukemia	wound healing
	(Haematologica. 1991. 82(2): 239-245). Inhibition of a	disorder
	decoy receptor could potentiate the effectiveness of the
	natural ligand.
sbg442358PROa	An embodiment of the invention is the use of	Cancer,
	sbg442358PROa useful in the prevention and treatment	autoimmune
	of cancers, cell proliferation, cardiovascular,	disorders,
	reproductive, immune, musculoskeletal, developmental	hemotopoietic
	and gastrointestinal disorders and inflammation. Close	disorders, wound
	homologues of sbg442358PROa are human protein	healing disorders
	B27231 and Drosophila LRR47 that also contains	and infections
	leucine-rich repeats (LRRs) motifs. LRR has been
	found in a variety of extracellular, membrane and
	cytoplasmic proteins and are believed to mediate
	specific protein-protein interactions and to function in
	cellular adhesion (Ntwasa, M., Buchanan, S. G. and
	Gay, N. J. Biochim. Biophys. Acta 1218 (2), 181-186
	(1994)).

[0122]

TABLE IV
Quantitative, Tissue-specific, mRNA expression detected using SybrMan
Quantitative, tissue-specific, mRNA expression patterns of the genes were measured using SYBR-
Green Quantitative PCR (Applied Biosystems, Foster City, CA; see Schmittgen T. D. et al.,
Analytical Biochemistry 285: 194-204, 2000) and human cDNAs prepared from various human
tissues. Gene-specific PCR primers were designed using the first nucleic acid sequence listed in the
Sequence List for each gene. Results are presented as the number of copies of each specific gene's
mRNA detected in 1 ng mRNA pool from each tissue. Two replicate mRNA measurements were
made from each tissue RNA.
Tissue-Specific mRNA Expression
(copies per ng mRNA; avg. ± range for 2 data points per tissue)
Gene						Skeletal
Name	Brain	Heart	Lung	Liver	Kidney	muscle	Intestine	Spleen/lymph	Placenta	Testis
Gene Name sbg237163LIPASE
sbg237163LIPASE	5 ± 0	8 ± 2	7 ± 2	−6 ± 1	5 ± 1	5 ± 2	4 ± 6	3 ± 2	1 ± 1	47 ± 1
Gene Name sbg251170CEAa
sbg251170CEAa	3 ± 1	19 ±	30 ±	−5 ± 3	3 ± 1	5 ± 5	21 ± 2	33 ± 4	22 ± 3	14 ± 0
		1	5
In each gene's first subset table, two replicate measurements of gene of identification (GOI) mRNA
were measured from various human tissues (column 2 and 3). The average GOI mRNA copies of
the two replicates were made from each tissue RNA (column 4). The average amount of 18S rRNA
from each tissue RNA was measured (column 5) and used for normalization. To make each tissue
with the same amount of 50 ng of 18S rRNA, the normalization factor (column 6) was calculated
by dividing 50 ng with the amount of 18S rRNA measured from each tissue (column 5). The
mRNA copies per 50 ng of total RNA were obtained by multipling each GOI normalization factor
and average mRNA copies (column7).
Fold changes shown in each gene's second subset table were only calculated for disease tissues
which have a normal counterpart. There are blanks in the fold change column for all samples that
do not have counterparts. In addition, the fold change calculations are the fold change in the disease
sample as compared to the normal sample. Accordingly, there will not be a fold change calculation
next to any of the normal samples. For patient matched cancer pairs (colon, lung, and breast), each
tumor is compared to its specific normal counterpart. When patient-matched normal/disease pairs
do not exist, each disease sample was compared back to the average of all the normal samples of
that same tissue type. For example, normal brain from the same patient that provided Alzheimer's
brain is not applicable. Three normal brain samples and 4 Alzheimer's brain samples are used in the
fold change. Three normal samples were averaged, and each of the Alzheimer's samples was
compared back to that average.
Abbreviations
ALZ	Alzheimer's Disease
CT	CLONTECH (1020 East Meadow Circle Palo Alto, CA 94303-4230, USA)
KC	Sample prepared by GSK investigator
COPD	chronic obstructive pulmonary disease
endo	endothelial
VEGF	vascular endothelial growth factor
bFGF	basic fibroblast growth factor
BM	bone marrow
osteo	osteoblast
OA	osteoarthritis
RA	rheumatoid arthritis
PBL	peripheral blood lymphocytes
PBMNC	peripheral blood mononuclear cells
HIV	human immunodeficiency virus
HSV	Herpes simplex virus
HPV	human papilloma virus
Gene Name sbg389686WNT15a
Strong expression in Brain and dendritic cells. Brain expression may be from presence of glial cells.
Expression in RA and OA synovium along with dendritic cells suggests a role for this protein in
these diseases. Down regulation in ischemic and dilated heart indicates that replacement of protein
could be therapeutic.

[0123]

						copies of
						mRNA
						detected/
	Mean GOI	Mean GOI	Average	18S	50 ng/18S	50 ng
Sample	copies	copies	GOI	rRNA	rRNA	total
sbg389686WNT15a	(sample 1)	(sample 2)	Copies	(ng)	(ng)	RNA
Subcutaneous	0.00	0.00	0.00	3.06	16.34	0.00
Adipocytes Zenbio
Subcutaneous Adipose	0.00	1.71	0.86	0.96	52.36	44.76
Zenbio
Adrenal Gland Clontech	2.29	4.18	3.24	0.61	81.97	265.16
Whole Brain Clontech	698.52	625.01	661.77	7.24	6.91	4570.20
Fetal Brain Clontech	4.14	6.78	5.46	0.48	103.95	567.57
Cerebellum Clontech	2.02	3.63	2.83	2.17	23.04	65.09
Cervix	3.16	10.14	6.65	2.42	20.66	137.40
Colon	2.48	3.44	2.96	2.71	18.45	54.61
Endometrium	2.69	5.20	3.95	0.73	68.21	269.10
Esophagus	10.67	3.24	6.96	1.37	36.50	253.83
Heart Clontech	9.26	6.07	7.67	1.32	37.88	290.34
Hypothalamus	7.10	5.16	6.13	0.32	155.28	951.86
Ileum	2.04	10.37	6.21	2.58	19.38	120.25
Jejunum	36.78	27.16	31.97	6.60	7.58	242.20
Kidney	16.46	16.55	16.51	2.12	23.58	389.27
Liver	14.07	3.34	8.71	1.50	33.33	290.17
Fetal Liver Clontech	4.60	8.89	6.75	10.40	4.81	32.43
Lung	3.11	10.49	6.80	2.57	19.46	132.30
Mammary Gland	3.28	10.61	6.95	13.00	3.85	26.71
Clontech
Myometrium	1.79	13.84	7.82	2.34	21.37	166.99
Omentum	1.96	2.65	2.31	3.94	12.69	29.25
Ovary	4.50	1.71	3.11	4.34	11.52	35.77
Pancreas	3.40	2.41	2.91	0.81	61.80	179.54
Head of Pancreas	2.22	4.63	3.43	1.57	31.85	109.08
Parotid Gland	5.48	2.07	3.78	5.48	9.12	34.44
Placenta Clontech	15.15	12.80	13.98	5.26	9.51	132.84
Prostate	3.39	7.44	5.42	3.00	16.67	90.25
Rectum	2.98	3.94	3.46	1.23	40.65	140.65
Salivary Gland	3.24	1.61	2.43	7.31	6.84	16.59
Clontech
Skeletal Muscle	2.01	1.55	1.78	1.26	39.68	70.63
Clontech
Skin	2.69	3.45	3.07	1.21	41.32	126.86
Small Intestine	5.39	1.67	3.53	0.98	51.07	180.29
Clontech
Spleen	3.96	2.52	3.24	4.92	10.16	32.93
Stomach	1.08	5.33	3.21	2.73	18.32	58.70
Testis Clontech	3.27	2.88	3.08	0.57	87.87	270.21
Thymus Clontech	5.43	4.42	4.93	9.89	5.06	24.90
Thyroid	2.32	3.01	2.67	2.77	18.05	48.10
Trachea Clontech	1.64	4.25	2.95	9.71	5.15	15.16
Urinary Bladder	3.63	6.81	5.22	5.47	9.14	47.71
Uterus	31.55	11.10	21.33	5.34	9.36	199.67
			copies of
	Reg		mRNA
	number	Mean	detected/50 ng		Fold Change in
Sample	(GSK	GOI	total		Disease
sbg389686WNT15a	identifier)	copies	RNA	Sample	Population
colon normal GW98-167	21941	36.16	72.32	colon normal
colon tumor GW98-166	21940	71.5	143.00	colon tumor	1.977323009
colon normal GW98-178	22080	2.09	4.18	colon normal
colon tumor GW98- 177	22060	9.84	19.68	colon tumor	4.708133971
colon normal GW98-561	23514	13.09	26.18	colon normal
colon tumor GW98-560	23513	15.11	30.22	colon tumor	1.154316272
colon normal GW98-894	24691	8.62	17.24	colon normal
colon tumor GW98-893	24690	5.76	11.52	colon tumor	−1.496527778
lung normal GW98-3	20742	140.19	280.38	lung normal
lung tumor GW98-2	20741	1.67	3.34	lung tumor	−83.94610778
lung normal GW97-179	20677	60.54	121.08	lung normal
lung tumor GW97- 178	20676	135.62	271.24	lung tumor	2.240171787
lung normal GW98-165	21922	257.96	515.92	lung normal
lung tumor GW98-164	21921	61.69	123.38	lung tumor	−4.181552926
lung normal GW98-282	22584	49.3	98.60	lung normal
lung tumor GW98-281	22583	12.39	24.78	lung tumor	−3.979015335
breast normal GW00-392	28750	71.94	71.94	breast
				normal
breast tumor GW00-391	28746	41.4	82.80	breast tumor	1.150959133
breast normal GW00-413	28798	19.37	19.37	breast
				normal
breast tumor GW00-412	28797	1.13	2.26	breast tumor	−8.57079646
breast normal GW00-	27592-95	8.19	8.19	breast
235:238				normal
breast tumor GW00-	27588-91	38.27	38.27	breast tumor	4.672771673
231:234
breast normal GW98-621	23656	77.26	154.52	breast
				normal
breast tumor GW98-620	23655	37.57	75.14	breast tumor	−2.056428001
brain normal BB99-542	25507	597.17	1194.34	brain normal
brain normal BB99-406	25509	104.34	208.68	brain normal
brain normal BB99-904	25546	282.15	564.30	brain normal
brain stage 5 ALZ BB99-	25502	84.26	168.52	brain stage 5	−3.891367988
874				ALZ
brain stage 5 ALZ BB99-	25503	247.01	494.02	brain stage 5	−1.327422641
887				ALZ
brain stage 5 ALZ BB99-	25504	173.02	346.04	brain stage 5	−1.895079567
862				ALZ
brain stage 5 ALZ BB99-	25542	253.73	507.46	brain stage 5	−1.292266057
927				ALZ
CT lung KC	normal	146.22	292.44	CT lung
lung 26 KC	normal	150.46	150.46	lung 26
lung 27 KC	normal	0	0.00	lung 27
lung 24 KC	COPD	4.76	4.76	lung 24	−23.36292017
lung 28 KC	COPD	10.06	10.06	lung 28	−11.05442346
lung 23 KC	COPD	2.75	2.75	lung 23	−40.43909091
lung 25 KC	COPD	1.93	1.93	lung 25
asthmatic lung	29321	20.88	20.88	asthmatic	−5.326029693
ODO3112				lung
asthmatic lung	29323	133.29	266.58	asthmatic	2.397140481
ODO3433				lung
asthmatic lung	29322	322.77	645.54	asthmatic	5.804824315
ODO3397				lung
asthmatic lung	29325	43.52	87.04	asthmatic	−1.277659697
ODO4928				lung
endo cells KC	control	1.89	1.89	endo cells
endo VEGF KC		0	0.00	endo VEGF	−1.89
endo bFGF KC		1.17	1.17	endo bFGF	−1.615384615
heart Clontech	normal	153.9	307.80	heart
heart (T-1) ischemic	29417	137.74	275.48	heart T-1	−1.117322492
heart (T-14) non-	29422	87.79	175.58	heart T-14	−1.753047044
obstructive DCM
heart (T-3399) DCM	29426	43.68	87.36	heart T-3399	−3.523351648
adenoid GW99-269	26162	17.62	35.24	adenoid
tonsil GW98-280	22582	52.34	104.68	tonsil
T cells PC00314	28453	8.45	16.90	T cells
PBMNC KC		1.99	1.99	PBMNC
monocyte KC		4.74	9.48	monocyte
B cells PC00665	28455	7.65	15.30	B cells
dendritic cells 28441		194.97	389.94	dendritic
				cells
neutrophils	28440	2.13	2.13	neutrophils
eosinophils	28446	7.25	14.50	eosinophils
BM unstim KC		0	0.00	BM unstim
BM stim KC		0	0.00	BM stim	0
osteo dif KC		1.48	1.48	osteo dif
osteo undif KC		7.41	7.41	osteo undif	5.006756757
chondrocytes		26.64	66.60	chondrocytes
OA Synovium IP12/01	29462	476.3	476.30	OA
				Synovium
OA Synovium NP10/01	29461	151.36	302.72	OA
				Synovium
OA Synovium NP57/00	28464	165.01	330.02	OA
				Synovium
RA Synovium NP03/01	28466	84.02	168.04	RA
				Synovium
RA Synovium NP71/00	28467	184.75	369.50	RA
				Synovium
RA Synovium NP45/00	28475	223.3	446.60	RA
				Synovium
OA bone (biobank)	29217	72.31	72.31	OA bone
				(biobank)
OA bone Sample 1	J. Emory	10.46	20.92	OA bone
OA bone Sample 2	J. Emory	111.79	223.58	OA bone
Cartilage (pool)	Normal	215.54	431.08	Cartilage
				(pool)
Cartilage (pool)	OA	81.85	163.70	Cartilage	−2.633353696
				(pool)
PBL unifected	28441	2.31	4.62	PBL
				unifected
PBL HIV IIIB	28442	2.28	4.56	PBL HIV	−1.013157895
				IIIB
MRC5 uninfected	29158	2.37	4.74	MRC5
(100%)				uninfected
				(100%)
MRC5 HSV strain F	29178	37.5	75.00	MRC5 HSV	15.82278481
				strain F
W12 cells	29179	0.93	1.86	W12 cells
Keratinocytes	29180	1.33	2.66	Keratinocytes

[0124]

Gene Name sbg389686WNT15a
                  Fold Change in Disease
                  Population Relative to
Disease tissues   Normal
colon tumor       1.98
colon tumor       4.71
colon tumor       1.15
colon tumor       −1.50
lung tumor        −83.95
lung tumor        2.24
lung tumor        −4.18
lung tumor        −3.98
breast tumor      1.15
breast tumor      −8.57
breast tumor      4.67
breast tumor      −2.06
brain stage 5 ALZ −3.89
brain stage 5 ALZ −1.33
brain stage 5 ALZ −1.90
brain stage 5 ALZ −1.29
lung 24           −23.36
lung 28           −11.05
lung 23           −40.44
asthmatic lung    −5.33
asthmatic lung    2.40
asthmatic lung    5.80
asthmatic lung    −1.28
endo VEGF         −1.89
endo bFGF         −1.62
heart T-1         −1.12
heart T-14        −1.75
heart T-3399      −3.52
BM stim           0.00
osteo undif       5.01
Cartilage (pool)  −2.63
PBL HIV IIIB      −1.01
MRC5 HSV strain F 15.82

[0125] Gene Name sbg236015LIPASE

[0126] Strongly expressed in neutrophils and eosinophils suggesting an immune system function. Additional expression is seen in RA and OA synovium and 1/3 OA bone samples. This suggests an involvement of 236015 in RA and OA. The high expression in skin when taken together with expression in neutrophils and eosinophils suggests possible involvement in immune pathologies of the skin ie. Eosinophilia, psoriasis and eczema. The expression in eosinophils also suggests involvement in allergic reactions. Expression in neutrophils suggests role in anti-infectives.

						copies of
						mRNA
					50 ng/	detected/
	Mean GOI	Mean GOI	Average	18S	18S	50 ng
Sample	copies	copies	GOI	rRNA	rRNA	total
sbg236015LIPASE	(sample 1)	(sample 2)	Copies	(ng)	(ng)	RNA
Subcutaneous	0.00	11.45	5.73	3.06	16.34	93.55
Adipocytes Zenbio
Subcutaneous Adipose	0.00	1.33	0.67	0.96	52.36	34.82
Zenbio
Adrenal Gland Clontech	0.52	5.04	2.78	0.61	81.97	227.87
Whole Brain Clontech	15.73	14.55	15.14	7.24	6.91	104.56
Fetal Brain Clontech	1.02	0.94	0.98	0.48	103.95	101.87
Cerebellum Clontech	0.38	0.39	0.39	2.17	23.04	8.87
Cervix	16.33	20.03	18.18	2.42	20.66	375.62
Colon	32.41	50.89	41.65	2.71	18.45	768.45
Endometrium	0.40	0.42	0.41	0.73	68.21	27.97
Esophagus	5.45	22.47	13.96	1.37	36.50	509.49
Heart Clontech	0.92	0.00	0.46	1.32	37.88	17.42
Hypothalamus	0.50	1.59	1.05	0.32	155.28	162.27
Ileum	41.95	1.51	21.73	2.58	19.38	421.12
Jejunum	7.59	15.40	11.50	6.60	7.58	87.08
Kidney	5.32	6.82	6.07	2.12	23.58	143.16
Liver	12.64	19.46	16.05	1.50	33.33	535.00
Fetal Liver Clontech	10.02	5.90	7.96	10.40	4.81	38.27
Lung	22.86	24.78	23.82	2.57	19.46	463.42
Mammary Gland	1.53	20.56	11.05	13.00	3.85	42.48
Clontech
Myometrium	16.05	1.34	8.70	2.34	21.37	185.79
Omentum	8.33	9.88	9.11	3.94	12.69	115.55
Ovary	8.22	14.40	11.31	4.34	11.52	130.30
Pancreas	0.00	1.58	0.79	0.81	61.80	48.83
Head of Pancreas	0.00	1.98	0.99	1.57	31.85	31.53
Parotid Gland	5.30	11.45	8.38	5.48	9.12	76.41
Placenta Clontech	11.93	1.22	6.58	5.26	9.51	62.50
Prostate	0.00	0.00	0.00	3.00	16.67	0.00
Rectum	6.96	1.27	4.12	1.23	40.65	167.28
Salivary Gland	0.34	0.53	0.44	7.31	6.84	2.98
Clontech
Skeletal Muscle	176.88	0.41	88.65	1.26	39.68	3517.66
Clontech
Skin	95.17	147.16	121.17	1.21	41.32	5006.82
Small Intestine	0.35	1.31	0.83	0.98	51.07	42.39
Clontech
Spleen	105.73	80.76	93.25	4.92	10.16	947.61
Stomach	0.56	3.73	2.15	2.73	18.32	39.29
Testis Clontech	0.79	0.78	0.79	0.57	87.87	68.98
Thymus Clontech	22.00	22.48	22.24	9.89	5.06	112.44
Thyroid	0.65	0.48	0.57	2.77	18.05	10.20
Trachea Clontech	1.20	0.00	0.60	9.71	5.15	3.09
Urinary Bladder	5.59	8.67	7.13	5.47	9.14	65.17
Uterus	19.26	27.10	23.18	5.34	9.36	217.04
			copies of
	Reg		mRNA
	number	Mean	detected/50 ng		Fold Change in
Sample	(GSK	GOI	total		Disease
sbg236015LIPASE	identifier)	copies	RNA	Sample	Population
colon normal GW98-167	21941	58.7	117.40	colon normal
colon tumor GW98-166	21940	300.92	601.84	colon tumor	5.126405451
colon normal GW98-178	22080	8.78	17.56	colon normal
colon tumor GW98-177	22060	23.74	47.48	colon tumor	2.703872437
colon normal GW98-561	23514	27.1	54.20	colon normal
colon tumor GW98-560	23513	39.16	78.32	colon tumor	1.44501845
colon normal GW98-894	24691	10.15	20.30	colon normal
colon tumor GW98-893	24690	144.58	289.16	colon tumor	14.24433498
lung normal GW98-3	20742	165.8	331.60	lung normal
lung tumor GW98-2	20741	80.9	161.80	lung tumor	−2.049443758
lung normal GW97-179	20677	37.81	75.62	lung normal
lung tumor GW97-178	20676	109.72	219.44	lung tumor	2.90187781
lung normal GW98-165	21922	150.06	300.12	lung normal
lung tumor GW98-164	21921	169.73	339.46	lung tumor	1.131080901
lung normal GW98-282	22584	489.42	978.84	lung normal
lung tumor GW98-281	22583	188.22	376.44	lung tumor	−2.600255021
breast normal GW00-392	28750	44.86	44.86	breast
				normal
breast tumor GW00-391	28746	46.35	92.70	breast tumor	2.06642889
breast normal GW00-413	28798	16.35	16.35	breast
				normal
breast tumor GW00-412	28797	55.98	111.96	breast tumor	6.847706422
breast normal GW00-	27592-95	3.84	3.84	breast
235:238				normal
breast tumor GW00-	27588-91	35.8	35.80	breast tumor	9.322916667
231:234
breast normal GW98-621	23656	12.14	24.28	breast
				normal
breast tumor GW98-620	23655	44.85	89.70	breast tumor	3.694398682
brain normal BB99-542	25507	26.03	52.06	brain normal
brain normal BB99-406	25509	14.78	29.56	brain normal
brain normal BB99-904	25546	3.39	6.78	brain normal
brain stage 5 ALZ BB99-	25502	35.71	71.42	brain stage 5	2.423755656
874				ALZ
brain stage 5 ALZ BB99-	25503	9.11	18.22	brain stage 5	−1.617270399
887				ALZ
brain stage 5 ALZ BB99-	25504	8.18	16.36	brain stage 5	−1.801140994
862				ALZ
brain stage 5 ALZ BB99-	25542	46.37	92.74	brain stage 5	3.147285068
927				ALZ
CT lung KC	normal	80.77	161.54	CT lung
lung 26 KC	normal	233.65	233.65	lung 26
lung 27 KC	normal	75.27	75.27	lung 27
lung 24 KC	COPD	68.64	68.64	lung 24	−1.876821096
lung 28 KC	COPD	94.1	94.10	lung 28	−1.369022317
lung 23 KC	COPD	88.48	88.48	lung 23	−1.455978752
lung 25 KC	normal	44.84	44.84	lung 25
asthmatic lung ODO3112	29321	111.42	111.42	asthmatic	−1.156210734
				lung
asthmatic lung ODO3433	29323	566.5	1133.00	asthmatic	8.794876771
				lung
asthmatic lung ODO3397	29322	262.77	525.54	asthmatic	4.079487677
				lung
asthmatic lung ODO4928	29325	367.52	735.04	asthmatic	5.70572482
				lung
endo cells KC	control	3.23	3.23	endo cells
endo VEGF KC		3.41	3.41	endo VEGF	1.055727554
endo bFGF KC		0	0.00	endo bFGF	−3.23
heart Clontech	normal	0	0.00	heart
heart (T-1) ischemic	29417	35.96	71.92	heart T-1	71.92
heart (T-14) non-	29422	18.72	37.44	heart T-14	37.44
obstructive DCM
heart (T-3399) DCM	29426	37.97	75.94	heart T-3399	75.94
adenoid GW99-269	26162	14.17	28.34	adenoid
tonsil GW98-280	22582	51.21	102.42	tonsil
T cells PC00314	28453	111.1	222.20	T cells
PBMNC KC		162.01	162.01	PBMNC
monocyte KC		90.49	180.98	monocyte
B cells PC00665	28455	109.71	219.42	B cells
dendritic cells 28441		2.44	4.88	dendritic
				cells
neutrophils	28440	1110.91	1110.91	neutrophils
eosinophils	28446	835.72	1671.44	eosinophils
BM unstim KC		181.05	181.05	BM unstim
BM stim KC		93.96	93.96	BM stim	−1.92688378
osteo dif KC		0	0.00	osteo dif
osteo undif KC		0.72	0.72	osteo undif	0.72
chondrocytes		2.03	5.08	chondrocytes
OA Synovium IP12/01	29462	27.82	27.82	OA
				Synovium
OA Synovium NP10/01	29461	84.94	169.88	OA
				Synovium
OA Synovium NP57/00	28464	46.58	93.16	OA
				Synovium
RA Synovium NP03/01	28466	248.24	496.48	RA
				Synovium
RA Synovium NP71/00	28467	148.32	296.64	RA
				Synovium
RA Synovium NP45/00	28475	260.28	520.56	RA
				Synovium
OA bone (biobank)	29217	10.27	10.27	OA bone
				(biobank)
OA bone Sample 1	J. Emory	17.32	34.64	OA bone
OA bone Sample 2	J. Emory	657.01	1314.02	OA bone
Cartilage (pool)	Normal	59.17	118.34	Cartilage
				(pool)
Cartilage (pool)	OA	23.33	46.66	Cartilage	−2.53621946
				(pool)
PBL unifected	28441	23.51	47.02	PBL
				unifected
PBL HIV IIIB	28442	5.86	11.72	PBL HIV	−4.011945392
				IIIB
MRC5 uninfected	29158	3.79	7.58	MRC5
(100%)				uninfected
				(100%)
MRC5 HSV strain F	29178	80.19	160.38	MRC5 HSV	21.15831135
				strain F
W12 cells	29179	95.42	190.84	W12 cells
Keratinocytes	29180	16.18	32.36	Keratinocytes

[0127]

Gene Name sbg236015LIPASE
                  Fold Change in Disease
                  Population Relative to
Disease tissues   Normal
colon tumor       5.13
colon tumor       2.70
colon tumor       1.45
colon tumor       14.24
lung tumor        −2.05
lung tumor        2.90
lung tumor        1.13
lung tumor        −2.60
breast tumor      2.07
breast tumor      6.85
breast tumor      9.32
breast tumor      3.69
brain stage 5 ALZ 2.42
brain stage 5 ALZ −1.62
brain stage 5 ALZ −1.80
brain stage 5 ALZ 3.15
lung 24           −1.88
lung 28           −1.37
lung 23           −1.46
asthmatic lung    −1.16
asthmatic lung    8.79
asthmatic lung    4.08
asthmatic lung    5.71
endo VEGF         1.06
endo bFGF         −3.23
heart T-1         71.92
heart T-14        37.44
heart T-3399      75.94
BM stim           −1.93
osteo undif       0.72
Cartilage (pool)  −2.54
PBL HIV IIIB      −4.01
MRC5 HSV strain F 21.16

[0128] Gene Name sbg417005LAMININ

[0129] Expression in adenoid, tonsil and B-cells with corroborating expression in RA/OA samples and asthmatic lung (1/4) suggests involvement in these diseases. Strong expression in brain with overexpression in Alzheimer's disease indicates a role in AD. Down regulation in HSV infected cells suggests potential host cell factor. Expression in colon and lung normal/tumor pairs without corroborating expression in normal tissues suggests immune cell infiltrates.

						copies
						of
						mRNA
						detected/
	Mean GOI	Mean GOI	Average	18S	50 ng/18S	50 ng
Sample	copies	copies	GOI	rRNA	rRNA	total
sbg417005LAMININ	(sample 1)	(sample 2)	Copies	(ng)	(ng)	RNA
Subcutaneous	60.2785303	73.59679955	66.94	3.06	16.34	1093.75
Adipocytes Zenbio
Subcutaneous Adipose	3.032572965	1.985862153	2.51	0.96	52.36	131.37
Zenbio
Adrenal Gland	0.965703497	0.965703497	0.97	0.61	81.97	79.16
Clontech
Whole Brain Clontech	4131.557992	6997.879078	5564.72	7.24	6.91	38430.38
Fetal Brain Clontech	0.965703497	3.268211325	2.12	0.48	103.95	220.06
Cerebellum Clontech	3.301057867	17.3966665	10.35	2.17	23.04	238.45
Cervix	5.920484049	7.517891571	6.72	2.42	20.66	138.83
Colon	35.48962684	22.53180605	29.01	2.71	18.45	535.25
Endometrium	11.59757492	0.965703497	6.28	0.73	68.21	428.49
Esophagus	7.098528857	3.523216475	5.31	1.37	36.50	193.83
Heart Clontech	0.965703497	5.368977287	3.17	1.32	37.88	119.98
Hypothalamus	0.965703497	0.965703497	0.97	0.32	155.28	149.95
Ileum	30.81006847	14.15032296	22.48	2.58	19.38	435.66
Jejunum	44.08994058	30.29386314	37.19	6.60	7.58	281.76
Kidney	9.424973981	15.68529125	12.56	2.12	23.58	296.11
Liver	3.742288161	0.965703497	2.35	1.50	33.33	78.47
Fetal Liver Clontech	94.45949484	93.8962252	94.18	10.40	4.81	452.78
Lung	13.84782444	19.95367566	16.90	2.57	19.46	328.81
Mammary Gland	107.7956161	95.02632495	101.41	13.00	3.85	390.04
Clontech
Myometrium	12.50117866	14.93742804	13.72	2.34	21.37	293.15
Omentum	13.998213	22.03816357	18.02	3.94	12.69	228.66
Ovary	0.965703497	0.965703497	0.97	4.34	11.52	11.13
Pancreas	2.254750425	0.965703497	1.61	0.81	61.80	99.52
Head of Pancreas	0.965703497	0.965703497	0.97	1.57	31.85	30.75
Parotid Gland	25.8930892	14.85668173	20.37	5.48	9.12	185.90
Placenta Clontech	83.84029668	95.02632495	89.43	5.26	9.51	850.13
Prostate	8.047386733	15.18245262	11.61	3.00	16.67	193.58
Rectum	10.53572882	20.06385011	15.30	1.23	40.65	621.94
Salivary Gland	62.43024331	57.19623352	59.81	7.31	6.84	409.12
Clontech
Skeletal Muscle	1.376746214	0.965703497	1.17	1.26	39.68	46.48
Clontech
Skin	0.965703497	0.965703497	0.97	1.21	41.32	39.91
Small Intestine	0.965703497	0.965703497	0.97	0.98	51.07	49.32
Clontech
Spleen	0.965703497	5.740147492	3.35	4.92	10.16	34.07
Stomach	0.965703497	0.965703497	0.97	2.73	18.32	17.69
Testis Clontech	0.965703497	0.965703497	0.97	0.57	87.87	84.86
Thymus Clontech	258.7386545	207.7169358	233.23	9.89	5.06	1179.11
Thyroid	12.56849785	19.09489343	15.83	2.77	18.05	285.77
Trachea Clontech	24.35330878	31.87047641	28.11	9.71	5.15	144.76
Urinary Bladder	51.81831091	57.53035871	54.67	5.47	9.14	499.77
Uterus	13.12099559	14.61718971	13.87	5.34	9.36	129.86
			copies of
			mRNA
	Reg		detected/
	number		50 ng		Fold Change
Sample	(GSK	Mean GOI	total		in Disease
sbg417005LAMININ	identifier)	copies	RNA	Sample	Population
colon normal GW98-167	21941	15446.92728	30893.85	colon normal
colon tumor GW98-166	21940	23910.90415	47821.81	colon tumor	1.547939193
colon normal GW98-178	22080	14621.97321	29243.95	colon normal
colon tumor GW98-177	22060	2058.30396	4116.61	colon tumor	−7.10389403
colon normal GW98-561	23514	5590.900474	11181.80	colon normal
colon tumor GW98-560	23513	12318.10362	24636.21	colon tumor	2.203241442
colon normal GW98-894	24691	4478.692403	8957.38	colon normal
colon tumor GW98-893	24690	7546.100944	15092.20	colon tumor	1.684889308
lung normal GW98-3	20742	23910.90415	47821.81	lung normal
lung tumor GW98-2	20741	35021.23317	70042.47	lung tumor	1.464655328
lung normal GW97-179	20677	23341.61421	46683.23	lung normal
lung tumor GW97-178	20676	24103.90252	48207.81	lung tumor	1.032657909
lung normal GW98-165	21922	18374.41273	36748.83	lung normal
lung tumor GW98-164	21921	34735.19726	69470.39	lung tumor	1.890411289
lung normal GW98-282	22584	3002.298467	6004.60	lung normal
lung tumor GW98-281	22583	3519.560955	7039.12	lung tumor	1.172288829
breast normal GW00-392	28750	5978.671937	5978.67	breast
				normal
breast tumor GW00-391	28746	5674.721186	11349.44	breast tumor	1.898321649
breast normal GW00-413	28798	1523.643258	1523.64	breast
				normal
breast tumor GW00-412	28797	956.0902914	1912.18	breast tumor	1.255005444
breast normal GW00-	27592-95	760.6128764	760.61	breast
235:238				normal
breast tumor GW00-	27588-91	4192.50003	4192.50	breast tumor	5.51200244
231:234
breast normal GW98-621	23656	5674.721186	11349.44	breast
				normal
breast tumor GW98-620	23655	8017.202071	16034.40	breast tumor	1.412792243
brain normal BB99-542	25507	791.7818289	1583.56	brain normal
brain normal BB99-406	25509	524.990001	1049.98	brain normal
brain normal BB99-904	25546	396.8655236	793.73	brain normal
brain stage 5 ALZ BB99-	25502	3203.498645	6407.00	brain stage 5	5.608243725
874				ALZ
brain stage 5 ALZ BB99-	25503	3925.505917	7851.01	brain stage 5	6.872234505
887				ALZ
brain stage 5 ALZ BB99-	25504	1502.651942	3005.30	brain stage 5	2.630635833
862				ALZ
brain stage 5 ALZ BB99-	25542	1555.711325	3111.42	brain stage 5	2.723524884
927				ALZ
CT lung KC	normal	3730.249874	7460.50	CT lung
lung 26 KC	normal	286.3143862	286.31	lung 26
lung 27 KC	normal	72.30560941	72.31	lung 27
lung 24 KC	COPD	28.47771374	28.48	lung 24	−69.25877363
lung 28 KC	COPD	66.98006875	66.98	lung 28	−29.44654382
lung 23 KC	COPD	57.53035871	57.53	lung 23	−34.28331708
lung 25 KC	COPD	70.20637402	70.21	lung 25
asthmatic lung	29321	2304.915385	2304.92	asthmatic	1.168624722
ODO3112				lung
asthmatic lung	29323	3112.377018	6224.75	asthmatic	3.156038395
ODO3433				lung
asthmatic lung	29322	21892.2071	43784.41	asthmatic	22.19931768
ODO3397				lung
asthmatic lung	29325	5268.438364	10536.88	asthmatic	5.34234563
ODO4928				lung
endo cells KC	control	396.8655236	396.87	endo cells
endo VEGF KC		157.1987188	157.20	endo VEGF	−2.524610421
endo bFGF KC		518.1542863	518.15	endo bFGF	1.305616778
heart Clontech	normal	1865.302957	3730.61	heart
heart (T-1) ischemic	29417	3757.505456	7515.01	heart T-1	2.014421005
heart (T-14) non-	29422	1633.333543	3266.67	heart T-14	−1.142022072
obstructive DCM
heart (T-3399) DCM	29426	2938.226492	5876.45	heart T-3399	1.575200683
adenoid GW99-269	26162	1238.725105	2477.45	adenoid
tonsil GW98-280	22582	2288.625236	4577.25	tonsil
T cells PC00314	28453	61.34444995	122.69	T cells
PBMNC KC		5.341492957	5.34	PBMNC
monocyte KC		3.576686692	7.15	monocyte
B cells PC00665	28455	716.2601536	1432.52	B cells
dendritic cells 28441		32.23243314	64.46	dendritic
				cells
neutrophils	28440	32.9693996	32.97	neutrophils
eosinophils	28446	1.444144312	2.89	eosinophils
BM unstim KC		5.951115795	5.95	BM unstim
BM stim KC		11.72233235	11.72	BM stim	1.969770503
osteo dif KC		10.20495465	10.20	osteo dif
osteo undif KC		8.526098078	8.53	osteo undif	−1.196907959
chondrocytes		14621.97321	36554.93	chondrocytes
OA Synovium IP12/01	29462	5549.480142	5549.48	OA
				Synovium
OA Synovium NP10/01	29461	3545.197127	7090.39	OA
				Synovium
OA Synovium NP57/00	28464	4223.325454	8446.65	OA
				Synovium
RA Synovium NP03/01	28466	1221.845309	2443.69	RA
				Synovium
RA Synovium NP71/00	28467	4892.67872	9785.36	RA
				Synovium
RA Synovium NP45/00	28475	1080.396739	2160.79	RA
				Synovium
OA bone (biobank)	29217	995.7612933	995.76	OA bone
				(biobank)
OA bone Sample 1	J. Emory	982.3483914	1964.70	OA bone
OA bone Sample 2	J. Emory	472.8535333	945.71	OA bone
Cartilage (pool)	Normal	1213.496434	2426.99	Cartilage
				(pool)
Cartilage (pool)	OA	697.4302173	1394.86	Cartilage	−1.73995391
				(pool)
PBL unifected	28441	161.1142664	322.23	PBL
				unifected
PBL HIV IIIB	28442	191.5686557	383.14	PBL HIV	1.189023542
				IIIB
MRC5 uninfected	29158	5934.220593	11868.44	MRC5
(100%)				uninfected
				(100%)
MRC5 HSV strain F	29178	50.63206269	101.26	MRC5 HSV	−117.2028213
				strain F
W12 cells	29179	13843.2955	27686.59	W12 cells
Keratinocytes	29180	11849.9156	23699.83	Keratinocytes

[0130]

Gene Name sbg417005LAMININ
                  Fold Change in Disease
                  Population Relative to
Disease tissues   Normal
colon tumor       1.55
colon tumor       −7.10
colon tumor       2.20
colon tumor       1.68
lung tumor        1.46
lung tumor        1.03
lung tumor        1.89
lung tumor        1.17
breast tumor      1.90
breast tumor      1.26
breast tumor      5.51
breast tumor      1.41
brain stage 5 ALZ 5.61
brain stage 5 ALZ 6.87
brain stage 5 ALZ 2.63
brain stage 5 ALZ 2.72
lung 24           −69.26
lung 28           −29.45
lung 23           −34.28
asthmatic lung    1.17
asthmatic lung    3.16
asthmatic lung    22.20
asthmatic lung    5.34
endo VEGF         −2.52
endo bFGF         1.31
heart T-1         2.01
heart T-14        −1.14
heart T-3399      1.58
BM stim           1.97
osteo undif       −1.20
Cartilage (pool)  −1.74
PBL HIV IIIB      1.19
MRC5 HSV strain F −117.20

[0131] Gene Name sbg425649KINASEa

[0132] Strongly expressed in neutrophils and eosinophils suggesting function in immune system such as involvement in allergic reactions and anti-infective. Lower expression in T-cells. Expression in 2/3 OA bone samples indicate a role in OA. Strongly expressed in rectum and skeletal muscle, unknown function.

						copies of
						mRNA
					50	detected/
	Mean GOI	Mean GOI	Average	18S	ng/18S	50 ng
Sample	copies	copies	GOI	rRNA	rRNA	total
sbg425649KINASEa	(sample 1)	(sample 2)	Copies	(ng)	(ng)	RNA
Subcutaneous	0.00	0.03	0.02	3.06	16.34	0.25
Adipocytes Zenbio
Subcutaneous Adipose	0.00	0.00	0.00	0.96	52.36	0.00
Zenbio
Adrenal Gland Clontech	0.23	0.00	0.12	0.61	81.97	9.43
Whole Brain Clontech	163.64	47.63	105.64	7.24	6.91	729.52
Fetal Brain Clontech	0.47	0.00	0.24	0.48	103.95	24.43
Cerebellum Clontech	0.00	0.00	0.00	2.17	23.04	0.00
Cervix	5.54	0.00	2.77	2.42	20.66	57.23
Colon	0.70	0.00	0.35	2.71	18.45	6.46
Endometrium	0.33	0.06	0.20	0.73	68.21	13.30
Esophagus	0.35	0.47	0.41	1.37	36.50	14.96
Heart Clontech	0.00	0.00	0.00	1.32	37.88	0.00
Hypothalamus	0.00	0.00	0.00	0.32	155.28	0.00
Ileum	0.00	4.49	2.25	2.58	19.38	43.51
Jejunum	0.29	0.73	0.51	6.60	7.58	3.86
Kidney	0.00	0.00	0.00	2.12	23.58	0.00
Liver	10.48	5.64	8.06	1.50	33.33	268.67
Fetal Liver Clontech	8.56	0.00	4.28	10.40	4.81	20.58
Lung	0.00	0.00	0.00	2.57	19.46	0.00
Mammary Gland	0.00	0.00	0.00	13.00	3.85	0.00
Clontech
Myometrium	8.61	5.00	6.81	2.34	21.37	145.41
Omentum	0.23	10.99	5.61	3.94	12.69	71.19
Ovary	4.48	4.62	4.55	4.34	11.52	52.42
Pancreas	0.27	0.00	0.14	0.81	61.80	8.34
Head of Pancreas	0.11	0.04	0.08	1.57	31.85	2.39
Parotid Gland	0.69	4.51	2.60	5.48	9.12	23.72
Placenta Clontech	10.58	0.14	5.36	5.26	9.51	50.95
Prostate	9.74	6.18	7.96	3.00	16.67	132.67
Rectum	225.51	76.99	151.25	1.23	40.65	6148.37
Salivary Gland	60.93	67.22	64.08	7.31	6.84	438.27
Clontech
Skeletal Muscle	749.28	29.78	389.53	1.26	39.68	15457.54
Clontech
Skin	0.00	4.46	2.23	1.21	41.32	92.15
Small Intestine	0.73	0.00	0.37	0.98	51.07	18.64
Clontech
Spleen	4.10	8.60	6.35	4.92	10.16	64.53
Stomach	4.24	19.28	11.76	2.73	18.32	215.38
Testis Clontech	10.11	6.34	8.23	0.57	87.87	722.76
Thymus Clontech	2.79	5.35	4.07	9.89	5.06	20.58
Thyroid	0.00	0.06	0.03	2.77	18.05	0.54
Trachea Clontech	5.24	14.14	9.69	9.71	5.15	49.90
Urinary Bladder	0.09	0.00	0.05	5.47	9.14	0.41
Uterus	27.26	7.61	17.44	5.34	9.36	163.25
			copies of
			mRNA
	Reg		detected/
	number	Mean	50 ng		Fold Change
Sample	(GSK	GOI	total		in Disease
sbg425649KINASEa	identifier)	copies	RNA	Sample	Population
colon normal GW98-167	21941	11.11	22.22	colon normal
colon tumor GW98-166	21940	7.3	14.60	colon tumor	−1.521917808
colon normal GW98-178	22080	0	0.00	colon normal
colon tumor GW98-177	22060	2.57	5.14	colon tumor	5.14
colon normal GW98-561	23514	0	0.00	colon normal
colon tumor GW98-560	23513	0	0.00	colon tumor	0
colon normal GW98-894	24691	2.71	5.42	colon normal
colon tumor GW98-893	24690	8.51	17.02	colon tumor	3.140221402
lung normal GW98-3	20742	1.78	3.56	lung normal
lung tumor GW98-2	20741	0	0.00	lung tumor	−3.56
lung normal GW97-179	20677	3.18	6.36	lung normal
lung tumor GW97-178	20676	2.64	5.28	lung tumor	−1.204545455
lung normal GW98-165	21922	6.46	12.92	lung normal
lung tumor GW98-164	21921	19.99	39.98	lung tumor	3.094427245
lung normal GW98-282	22584	31.56	63.12	lung normal
lung tumor GW98-281	22583	7.47	14.94	lung tumor	−4.224899598
breast normal GW00-392	28750	5.68	5.68	breast
				normal
breast tumor GW00-391	28746	2.87	5.74	breast tumor	1.01056338
breast normal GW00-413	28798	1.66	1.66	breast
				normal
breast tumor GW00-412	28797	1.99	3.98	breast tumor	2.397590361
breast normal GW00-	27592-95	0	0.00	breast
235:238				normal
breast tumor GW00-	27588-91	2.19	2.19	breast tumor	2.19
231:234
breast normal GW98-621	23656	4.72	9.44	breast
				normal
breast tumor GW98-620	23655	0	0.00	breast tumor	−9.44
brain normal BB99-542	25507	28.9	57.80	brain normal
brain normal BB99-406	25509	24.84	49.68	brain normal
brain normal BB99-904	25546	6.92	13.84	brain normal
brain stage 5 ALZBB99-	25502	23.65	47.30	brain stage 5	1.169634026
874				ALZ
brain stage 5 ALZ BB99-	25503	28.68	57.36	brain stage 5	1.418397626
887				ALZ
brain stage 5 ALZ BB99-	25504	18.18	36.36	brain stages 5	−1.112211221
862				ALZ
brain stage 5 ALZ BB99-	25542	14.18	28.36	brain stage 5	−1.425952045
927				ALZ
CT lung KC	normal	29.45	58.90	CT lung
lung 26 KC	normal	2.47	2.47	lung 26
lung 27 KC	normal	0	0.00	lung 27
lung 24 KC	COPD	0	0.00	lung 24	−15.3425
lung 28 KC	COPD	0.3	0.30	lung 28	−51.14166667
lung 23 KC	COPD	0	0.00	lung 23	−15.3425
lung 25 KC	COPD	0	0.00	lung 25
asthmatic lung	29321	3.24	3.24	asthmatic	−4.735339506
ODO3112				lung
asthmatic lung	29323	88.32	176.64	asthmatic	11.51311716
ODO3433				lung
asthmatic lung	29322	55.65	111.30	asthmatic	7.254358807
ODO3397				lung
asthmatic lung	29325	50.64	101.28	asthmatic	6.601270979
ODO4928				lung
endo cells KC	control	0	0.00	endo cells
endo VEGF KC		0	0.00	endo VEGF	0
endo bFGF KC		0	0.00	endo bFGF	0
heart Clontech	normal	15.26	30.52	heart
heart (T-1 ) ischemic	29417	0	0.00	heart T-1	−30.52
heart (T-14) non-	29422	3.69	7.38	heart T-14	−4.135501355
obstructive DCM
heart (T-3399) DCM	29426	0	0.00	heart T-3399	−30.52
adenoid GW99-269	26162	0	0.00	adenoid
tonsil GW98-280	22582	3.65	7.30	tonsil
T cells PC00314	28453	167.51	335.02	T cells
PBMNC KC		2.5	2.50	PBMNC
monocyte KC		2.37	4.74	monocyte
B cells PC00665	28455	0	0.00	B cells
dendritic cells 28441		0	0.00	dendritic
				cells
neutrophils	28440	1576.76	1576.76	neutrophils
eosinophils	28446	755.1	1510.20	eosinophils
BM unstim KC		14.87	14.87	BM unstim
BM stim KC		45.45	45.45	BM stim	3.056489576
osteo dif KC		0	0.00	osteo dif
osteo undif KC		0	0.00	osteo undif	0
chondrocytes		7.48	18.70	chondrocytes
OA Synovium IP12/01	29462	17.79	17.79	OA
				Synovium
OA Synovium NP10/01	29461	14.09	28.18	OA
				Synovium
OA Synovium NP57/00	28464	11.97	23.94	OA
				Synovium
RA Synovium NP03/01	28466	6.84	13.68	RA
				Synovium
RA Synovium NP71/00	28467	22.88	45.76	RA
				Synovium
RA Synovium NP45/00	28475	1.64	3.28	RA
				Synovium
OA bone (biobank)	29217	370.22	370.22	OA bone
				(biobank)
OA bone Sample 1	J. Emory	3.21	6.42	OA bone
OA bone Sample 2	J. Emory	311.65	623.30	OA bone
Cartilage (pool)	Normal	32.23	64.46	Cartilage
				(pool)
Cartilage (pool)	OA	2.87	5.74	Cartilage	−11.22996516
				(pool)
PBL unifected	28441	4.18	8.36	PBL
				unifected
PBL HIV IIIB	28442	0	0.00	PBL HIV	−8.36
				IIIB
MRC5 uninfected	29158	4.4	8.80	MRC5
(100%)				uninfected
				(100%)
MRC5 HSV strain F	29178	11.46	22.92	MRC5 HSV	2.604545455
				strain F
W12 cells	29179	0	0.00	W12 cells
Keratinocytes	29180	0	0.00	Keratinocytes

[0133] Gene Name sbg425649KINASEa

                  Fold Change in Disease
                  Population Relative to
Disease tissues   Normal
colon tumor       −1.52
colon tumor       5.14
colon tumor       0.00
colon tumor       3.14
lung tumor        −3.56
lung tumor        −1.20
lung tumor        3.09
lung tumor        −4.22
breast tumor      1.01
breast tumor      2.40
breast tumor      2.19
breast tumor      −9.44
brain stage 5 ALZ 1.17
brain stage 5 ALZ 1.42
brain stage 5 ALZ −1.11
brain stage 5 ALZ −1.43
lung 24           −15.34
lung 28           −51.14
lung 23           −15.34
asthmatic lung    −4.74
asthmatic lung    11.51
asthmatic lung    7.25
asthmatic lung    6.60
endo VEGF         0.00
endo bFGF         0.00
heart T-1         −30.52
heart T-14        −4.14
heart T-3399      −30.52
BM stim           3.06
osteo undif       0.00
Cartilage (pool)  −11.23
PBL HIV IIIB      −8.36
MRC5 HSV strain F 2.60

[0134] Gene Name sbg419582PROTOCADHERIN

[0135] Brain specific expression. No correlation with Alzheimer's disease. Low expression in RA and OA synovium but no corroborating expression in immune cells. Slightly upregulated in heart disease. Overexpressed in lung (1/4) and breast (1/4) tumors.

						copies of
						mRNA
					50 ng/	detected/
Sample	Mean GOI	Mean GOI	Average	18S	18S	50 ng
sbg419582PROTOCA	copies	copies	GOI	rRNA	rRNA	total
DHERIN	(sample 1)	(sample 2)	Copies	(ng)	(ng)	RNA
Subcutaneous	18.18	23.43	20.81	3.06	16.34	339.95
Adipocytes Zenbio
Subcutaneous Adipose	0.11	0.33	0.22	0.96	52.36	11.52
Zenbio
Adrenal Gland Clontech	1.8	1.06	1.43	0.61	81.97	117.21
Whole Brain Clontech	10913.92	10314.42	10614.17	7.24	6.91	73302.28
Fetal Brain Clontech	0.31	4.68	2.50	0.48	103.95	259.36
Cerebellum Clontech	0.1	4.58	2.34	2.17	23.04	53.92
Cervix	0.22	1.22	0.72	2.42	20.66	14.88
Colon	0.31	13.73	7.02	2.71	18.45	129.52
Endometrium	0.1	0.58	0.34	0.73	68.21	23.19
Esophagus	2.21	1.96	2.09	1.37	36.50	76.09
Heart Clontech	0.32	0	0.16	1.32	37.88	6.06
Hypothalamus	0.15	1.2	0.68	0.32	155.28	104.81
Ileum	2.77	1.03	1.90	2.58	19.38	36.82
Jejunum	0.26	1.18	0.72	6.60	7.58	5.45
Kidney	1.99	0.28	1.14	2.12	23.58	26.77
Liver	7.59	12.42	10.01	1.50	33.33	333.50
Fetal Liver Clontech	18.75	11.04	14.90	10.40	4.81	71.61
Lung	7.19	0.71	3.95	2.57	19.46	76.85
Mammary Gland	88.14	97.88	93.01	13.00	3.85	357.73
Clontech
Myometrium	0.51	4.8	2.66	2.34	21.37	56.73
Omentum	7.52	2.19	4.86	3.94	12.69	61.61
Ovary	13.46	4.84	9.15	4.34	11.52	105.41
Pancreas	0.49	1.02	0.76	0.81	61.80	46.66
Head of Pancreas	0.29	0.15	0.22	1.57	31.85	7.01
Parotid Gland	6.09	6.19	6.14	5.48	9.12	56.02
Placenta Clontech	10.67	2.35	6.51	5.26	9.51	61.88
Prostate	2.02	3.59	2.81	3.00	16.67	46.75
Rectum	0.54	7.25	3.90	1.23	40.65	158.33
Salivary Gland	20.51	13.73	17.12	7.31	6.84	117.10
Clontech
Skeletal Muscle	1.06	0.79	0.93	1.26	39.68	36.71
Clontech
Skin	13.09	0.6	6.85	1.21	41.32	282.85
Small Intestine	0.11	2.47	1.29	0.98	51.07	65.88
Clontech
Spleen	1.05	11	6.03	4.92	10.16	61.23
Stomach	0.95	1.3	1.13	2.73	18.32	20.60
Testis Clontech	2.82	3.19	3.01	0.57	87.87	264.06
Thymus Clontech	117.82	118.81	118.32	9.89	5.06	598.15
Thyroid	2.34	2.29	2.32	2.77	18.05	41.79
Trachea Clontech	8.72	9.37	9.05	9.71	5.15	46.58
Urinary Bladder	14.23	16.82	15.53	5.47	9.14	141.91
Uterus	1.49	27.26	14.38	5.34	9.36	134.60
			copies of
	Reg		mRNA
Sample	number	Mean	detected/50 ng		Fold Change in
sbg419582PROTOCA	(GSK	GOI	total		Disease
DHERIN	identifier)	copies	RNA	Sample	Population
colon normal GW98-167	21941	464.48	928.96	colon normal
colon tumor GW98-166	21940	84.22	168.44	colon tumor	−5.515079554
colon normal GW98-178	22080	32.8	65.60	colon normal
colon tumor GW98-177	22060	44.71	89.42	colon tumor	1.363109756
colon normal GW98-561	23514	135.5	271.00	colon normal
colon tumor GW98-560	23513	78.51	157.02	colon tumor	−1.72589479
colon normal GW98-894	24691	454.16	908.32	colon normal
colon tumor GW98-893	24690	51.37	102.74	colon tumor	−8.840957757
lung normal GW98-3	20742	60.35	120.70	lung normal
lung tumor GW98-2	20741	101.98	203.96	lung tumor	1.689809445
lung normal GW97-179	20677	264	528.00	lung normal
lung tumor GW97-178	20676	78.49	156.98	lung tumor	−3.363485794
lung normal GW98-165	21922	88.19	176.38	lung normal
lung tumor GW98-164	21921	7554.58	15109.16	lung tumor	85.66254677
lung normal GW98-282	22584	344.2	688.40	lung normal
lung tumor GW98-281	22583	45.51	91.02	lung tumor	−7.563172929
breast normal GW00-392	28750	132.43	132.43	breast
				normal
breast tumor GW00-391	28746	98.14	196.28	breast tumor	1.482141509
breast normal GW00-413	28798	154.37	154.37	breast
				normal
breast tumor GW00-412	28797	1289.09	2578.18	breast tumor	16.70130207
breast normal GW00-	27592-95	18.63	18.63	breast
235:238				normal
breast tumor GW00-	27588-91	133.52	133.52	breast tumor	7.166935051
231:234
breast normal GW98-621	23656	1334.91	2669.82	breast
				normal
breast tumor GW98-620	23655	212.39	424.78	breast tumor	−6.285182918
brain normal BB99-542	25507	6816.47	13632.94	brain normal
brain normal BB99-406	25509	1984.48	3968.96	brain normal
brain normal BB99-904	25546	2805.82	5611.64	brain normal
brain stage 5 ALZ BB99-	25502	467.59	935.18	brain stage 5	−8.274178946
874				ALZ
brain stage 5 ALZ BB99-	25503	3104.22	6208.44	brain stage 5	−1.24634315
887				ALZ
brain stage 5 ALZ BB99-	25504	1889.81	3779.62	brain stage 5	−2.047255191
862				ALZ
brain stage 5 ALZ BB99-	25542	2902.29	5804.58	brain stage 5	−1.333058837
927				ALZ
CT lung KC	normal	103.32	206.64	CT lung
lung 26 KC	normal	1.13	1.13	lung 26
lung 27 KC	normal	1.51	1.51	lung 27
lung 24 KC	COPD	1.47	1.47	lung 24	−35.82312925
lung 28 KC	COPD	0	0.00	lung 28	−52.66
lung 23 KC	COPD	1.91	1.91	lung 23	−27.57068063
lung 25 KC	COPD	1.36	1.36	lung 25
asthmatic lung	29321	2.68	2.68	asthmatic	−19.64925373
ODO3112				lung
asthmatic lung	29323	3.25	6.50	asthmatic	−8.101538462
ODO3433				lung
asthmatic lung	29322	26.23	52.46	asthmatic	−1.003812429
ODO3397				lung
asthmatic lung	29325	7.15	14.30	asthmatic	−3.682517483
ODO4928				lung
endo cells KC	control	15.9	15.90	endo cells
endo VEGF KC		8.26	8.26	endo VEGF	−1.924939467
endo bFGF KC		2.01	2.01	endo bFGF	−7.910447761
heart Clontech	normal	7.9	15.80	heart
heart (T-1) ischemic	29417	67.47	134.94	heart T-1	8.540506329
heart (T-14) non-	29422	106.83	213.66	heart T-14	13.52278481
obstructive DCM
heart (T-3399) DCM	29426	425.28	850.56	heart T-3399	53.83291139
adenoid GW99-269	26162	15.98	31.96	adenoid
tonsil GW98-280	22582	17.95	35.90	tonsil
T cells PC00314	28453	3.18	6.36	T cells
PBMNC KC		0	0.00	PBMNC
monocyte KC		0.81	1.62	monocyte
B cells PC00665	28455	2.74	5.48	B cells
dendritic cells 28441		0	0.00	dendritic
				cells
neutrophils	28440	0	0.00	neutrophils
eosinophils	28446	0	0.00	eosinophils
BM unstim KC		0	0.00	BM unstim
BM stim KC		0	0.00	BM stim	0
osteo dif KC		2.34	2.34	osteo dif
osteo undif KC		0	0.00	osteo undif	−2.34
chondrocytes		145.14	362.85	chondrocytes
OA Synovium IP12/01	29462	320.78	320.78	OA
				Synovium
OA Synovium NP10/01	29461	396.85	793.70	OA
				Synovium
OA Synovium NP57/00	28464	329.87	659.74	OA
				Synovium
RA Synovium NP03/01	28466	103.85	207.70	RA
				Synovium
RA Synovium NP71/00	28467	617.72	1235.44	RA
				Synovium
RA Synovium NP45/00	28475	63.13	126.26	RA
				Synovium
OA bone (biobank)	29217	3.19	3.19	OA bone
				(biobank)
OA bone Sample 1	J. Emory	126.87	253.74	OA bone
OA bone Sample 2	J. Emory	44.76	89.52	OA bone
Cartilage (pool)	Normal	502.66	1005.32	Cartilage
				(pool)
Cartilage (pool)	OA	206.76	413.52	Cartilage	−2.431127878
				(pool)
PBL unifected	28441	0	0.00	PBL
				unifected
PBL HIV IIIB	28442	0	0.00	PBL HIV	0
				IIIB
MRC5 uninfected	29158	0	0.00	MRC5
(100%)				uninfected
				(100%)
MRC5 HSV strain F	29178	17.73	35.46	MRC5 HSV	35.46
				strain F
W12 cells	29179	0.62	1.24	W12 cells
Keratinocytes	29180	22.63	45.26	Keratinocytes

[0136]

Gene Name sbg419582PROTOCADHERIN
                  Fold Change in Disease
                  Population Relative to
Disease tissues   Normal
colon tumor       −5.52
colon tumor       1.36
colon tumor       −1.73
colon tumor       −8.84
lung tumor        1.69
lung tumor        −3.36
lung tumor        85.66
lung tumor        −7.56
breast tumor      1.48
breast tumor      16.70
breast tumor      7.17
breast tumor      −6.29
brain stage 5 ALZ −8.27
brain stage 5 ALZ −1.25
brain stage 5 ALZ −2.05
brain stage 5 ALZ −1.33
lung 24           −35.82
lung 28           −52.66
lung 23           −27.57
asthmatic lung    −19.65
asthmatic lung    −8.10
asthmatic lung    −1.00
asthmatic lung    −3.68
endo VEGF         −1.92
endo bFGF         −7.91
heart T-1         8.54
heart T-14        13.52
heart T-3399      53.83
BM stim           0.00
osteo undif       −2.34
Cartilage (pool)  −2.43
PBL HIV IIIB      0.00
MRC5 HSV strain F 35.46

[0137] Gene Name sbg453915TECTORINa

[0138] Very low expression overall. Expression in female reproductive tissues suggests a protein that may be secreted by these tissue types.

						copies of
						mRNA
						detected/
	Mean GOI	Mean GOI	Average	18S	50 ng/18S	50 ng
Sample	copies	copies	GOI	rRNA	rRNA	total
sbg453915TECTORINa	(sample 1)	(sample 2)	Copies	(ng)	(ng)	RNA
Subcutaneous	2.70	5.41	4.06	3.06	16.34	66.26
Adipocytes Zenbio
Subcutaneous Adipose	0.00	0.00	0.00	0.96	52.36	0.00
Zenbio
Adrenal Gland Clontech	3.75	5.67	4.71	0.61	81.97	386.07
Whole Brain Clontech	22.57	27.88	25.23	7.24	6.91	174.21
Fetal Brain Clontech	2.42	1.80	2.11	0.48	103.95	219.33
Cerebellum Clontech	0.00	1.93	0.97	2.17	23.04	22.24
Cervix	2.90	2.10	2.50	2.42	20.66	51.65
Colon	11.19	2.68	6.94	2.71	18.45	127.95
Endometrium	4.79	19.31	12.05	0.73	68.21	821.96
Esophagus	2.06	2.93	2.50	1.37	36.50	91.06
Heart Clontech	5.42	7.31	6.37	1.32	37.88	241.10
Hypothalamus	0.00	3.70	1.85	0.32	155.28	287.27
Ileum	3.72	18.75	11.24	2.58	19.38	217.73
Jejunum	28.49	49.80	39.15	6.60	7.58	296.55
Kidney	2.12	4.37	3.25	2.12	23.58	76.53
Liver	15.74	39.80	27.77	1.50	33.33	925.67
Fetal Liver Clontech	27.96	26.14	27.05	10.40	4.81	130.05
Lung	0.00	2.37	1.19	2.57	19.46	23.05
Mammary Gland	19.68	19.22	19.45	13.00	3.85	74.81
Clontech
Myometrium	3.40	1.71	2.56	2.34	21.37	54.59
Omentum	14.33	138.99	76.66	3.94	12.69	972.84
Ovary	46.55	37.80	42.18	4.34	11.52	485.89
Pancreas	4.26	2.19	3.23	0.81	61.80	199.32
Head of Pancreas	1.93	1.52	1.73	1.57	31.85	54.94
Parotid Gland	4.04	5.93	4.99	5.48	9.12	45.48
Placenta Clontech	3.69	15.48	9.59	5.26	9.51	91.11
Prostate	7.94	28.75	18.35	3.00	16.67	305.75
Rectum	11.09	3.41	7.25	1.23	40.65	294.72
Salivary Gland	0.00	1.45	0.73	7.31	6.84	4.96
Clontech
Skeletal Muscle	4.76	0.00	2.38	1.26	39.68	94.44
Clontech
Skin	0.00	1.39	0.70	1.21	41.32	28.72
Small Intestine	2.20	1.41	1.81	0.98	51.07	92.19
Clontech
Spleen	7.15	8.12	7.64	4.92	10.16	77.59
Stomach	1.98	0.00	0.99	2.73	18.32	18.13
Testis Clontech	6.83	2.61	4.72	0.57	87.87	414.76
Thymus Clontech	0.00	0.00	0.00	9.89	5.06	0.00
Thyroid	2.38	1.88	2.13	2.77	18.05	38.45
Trachea Clontech	1.71	9.25	5.48	9.71	5.15	28.22
Urinary Bladder	3.72	8.22	5.97	5.47	9.14	54.57
Uterus	74.31	73.54	73.93	5.34	9.36	692.18
			copies of
	Reg		mRNA
	number	Mean	detected/50 ng		Fold Change in
Sample	(GSK	GOI	total		Disease
sbg453915TECTORINa	identifier)	copies	RNA	Sample	Population
colon normal GW98-167	21941	131.15	262.30	colon normal
colon tumor GW98-166	21940	85.76	171.52	colon tumor	−1.529267724
colon normal GW98-178	22080	1.82	3.64	colon normal
colon tumor GW98-177	22060	10.14	20.28	colon tumor	5.571428571
colon normal GW98-561	23514	14.25	28.50	colon normal
colon tumor GW98-560	23513	9.89	19.78	colon tumor	−1.440849343
colon normal GW98-894	24691	32.05	64.10	colon normal
colon tumor GW98-893	24690	53.06	106.12	colon tumor	1.655538222
lung normal GW98-3	20742	6.9	13.80	lung normal
lung tumor GW98-2	20741	0.81	1.62	lung tumor	−8.518518519
lung normal GW97-179	20677	1.19	2.38	lung normal
lung tumor GW97-178	20676	0	0.00	lung tumor	−2.38
lung normal GW98-165	21922	0.91	1.82	lung normal
lung tumor GW98-164	21921	5.99	11.98	lung tumor	6.582417582
lung normal GW98-282	22584	5.93	11.86	lung normal
lung tumor GW98-281	22583	1.54	3.08	lung tumor	−3.850649351
breast normal GW00-392	28750	6.88	6.88	breast
				normal
breast tumor GW00-391	28746	4.24	8.48	breast tumor	1.23255814
breast normal GW00-413	28798	0	0.00	breast
				normal
breast tumor GW00-412	28797	13.96	27.92	breast tumor	27.92
breast normal GW00-	27592-95	14.42	14.42	breast
235:238				normal
breast tumor GW00-	27588-91	0	0.00	breast tumor	−14.42
231:234
breast normal GW98-621	23656	5.81	11.62	breast
				normal
breast tumor GW98-620	23655	0	0.00	breast tumor	−11.62
brain normal BB99-542	25507	20.59	41.18	brain normal
brain normal BB99-406	25509	15.98	31.96	brain normal
brain normal BB99-904	25546	2.38	4.76	brain normal
brain stage 5 ALZ BB99-	25502	25.45	50.90	brain stage 5	1.960205392
874				ALZ
brain stage 5 ALZ BB99-	25503	35.78	71.56	brain stage 5	2.755840822
887				ALZ
brain stage 5 ALZ BB99-	25504	13.83	27.66	brain stage 5	1.06521181
862				ALZ
brain stage 5 ALZ BB99-	25542	21.67	43.34	brain stage 5	1.669062901
927				ALZ
CT lung KC	normal	6.52	13.04	CT lung
lung 26 KC	normal	2.1	2.10	lung 26
lung 27 KC	normal	0.84	0.84	lung 27
lung 24 KC	COPD	1.25	1.25	lung 24	−3.432
lung 28 KC	COPD	0	0.00	lung 28	−4.29
lung 23 KC	COPD	1.16	1.16	lung 23	−3.698275862
lung 25 KC	COPD	1.18	1.18	lung 25
asthmatic lung ODO3112	29321	4.9	4.90	asthmatic	1.142191142
				lung
asthmatic lung ODO3433	29323	0.83	1.66	asthmatic	−2.584337349
				lung
asthmatic lung ODO3397	29322	2.46	4.92	asthmatic	1.146853147
				lung
asthmatic lung ODO4928	29325	6	12.00	asthmatic	2.797202797
				lung
endo cells KC	control	2.52	2.52	endo cells
endo VEGF KC		1.28	1.28	endo VEGF	−1.96875
endo bFGF KC		0	0.00	endo bFGF	−2.52
heart Clontech	normal	0	0.00	heart
heart (T-1) ischemic	29417	3.58	7.16	heart T-1	7.16
heart (T-14) non-	29422	0	0.00	heart T-14	0
obstructive DCM
heart (T-3399)DCM	29426	0	0.00	heart T-3399	0
adenoid GW99-269	26162	2.29	4.58	adenoid
tonsil GW98-280	22582	1.85	3.70	tonsil
T cells PC00314	28453	4.29	8.58	T cells
PBMNC KC		0	0.00	PBMNC
monocyte KC		3.39	6.78	monocyte
B cells PC00665	28455	6.04	12.08	B cells
dendritic cells 28441		0.83	1.66	dendritic
				cells
neutrophils	28440	34.69	34.69	neutrophils
eosinophils	28446	2.86	5.72	eosinophils
BM unstim KC		0	0.00	BM unstim
BM stim KC		12.8	12.80	BM stim	12.8
osteo dif KC		0	0.00	osteo dif
osteo undif KC		0	0.00	osteo undif	0
chondrocytes		4.78	11.95	chondrocytes
OA Synovium IP12/01	29462	18.31	18.31	OA
				Synovium
OA Synovium NP10/01	29461	0	0.00	OA
				Synovium
OA Synovium NP57/00	28464	11.46	22.92	OA
				Synovium
RA Synovium NP03/01	28466	0.87	1.74	RA
				Synovium
RA Synovium NP71/00	28467	26.95	53.90	RA
				Synovium
RA Synovium NP45/00	28475	18.91	37.82	RA
				Synovium
OA bone (biobank)	29217	0	0.00	OA bone
				(biobank)
OA bone Sample 1	J. Emory	8.66	17.32	OA bone
OA bone Sample 2	J. Emory	7.8	15.60	OA bone
Cartilage (pool)	Normal	16.93	33.86	Cartilage
				(pool)
Cartilage (pool)	OA	6.39	12.78	Cartilage	−2.649452269
				(pool)
PBL unifected	28441	0	0.00	PBL
				unifected
PBL HIV IIIB	28442	1.15	2.30	PBL HIV	2.3
				IIIB
MRC5 uninfected	29158	0	0.00	MRC5
(100%)				uninfected
				(100%)
MRC5 HSV strain F	29178	70.84	141.68	MRC5 HSV	141.68
				strain F
W12 cells	29179	5.59	11.18	W12 cells
Keratinocytes	29180	0	0.00	Keratinocytes

[0139] Gene Name sbg453915TECTORINa

                  Fold Change in Disease
                  Population Relative to
Disease tissues   Normal
colon tumor       −1.53
colon tumor       5.57
colon tumor       −1.44
colon tumor       1.66
lung tumor        −8.52
lung tumor        −2.38
lung tumor        6.58
lung tumor        −3.85
breast tumor      1.23
breast tumor      27.92
breast tumor      −14.42
breast tumor      −11.62
brain stage 5 ALZ 1.96
brain stage 5 ALZ 2.76
brain stage 5 ALZ 1.07
brain stage 5 ALZ 1.67
lung 24           −3.43
lung 28           −4.29
lung 23           −3.70
asthmatic lung    1.14
asthmatic lung    −2.58
asthmatic lung    1.15
asthmatic lung    2.80
endo VEGF         −1.97
endo bFGF         −2.52
heart T-1         7.16
heart T-14        0.00
heart T-3399      0.00
BM stim           12.80
osteo undif       0.00
Cartilage (pool)  −2.65
PBL HIV IIIB      2.30
MRC5 HSV strain F 141.68

[0140] Gene Name SBh385630.antiinflam

[0141] Some expression in adenoid, tonsils and T-cells suggesting a role in the immune system. Expression in GI tissues suggests a role in the digestive system and potential role in diseases of the GI system such as EBD. Overexpression in lung (1/4) and colon tumors (1/4) suggesting a role in lung and colon cancer. Increased expression in ischemic and dilated heart samples indicating a role in Cardiovascular diseases that are consistent with cardiac hypertropby. Expression in whole brain but not localized to hypothalamus, cerebellum or cortex.

						copies of
						mRNA
						detected/
	Mean GOI	Mean GOI	Average	18S	50 ng/18S	50 ng
Sample	copies	copies	GOI	rRNA	rRNA	total
SBh385630.antiinflam	(sample 1)	(sample 2)	Copies	(ng)	(ng)	RNA
Subcutaneous	0.00	6.41	3.21	3.06	16.34	52.37
Adipocytes Zenbio
Subcutaneous Adipose	0.00	0.00	0.00	0.96	52.36	0.00
Zenbio
Adrenal Gland Clontech	8.40	0.00	4.20	0.61	81.97	344.26
Whole Brain Clontech	817.17	466.76	641.97	7.24	6.91	4433.46
Fetal Brain Clontech	3.80	0.00	1.90	0.48	103.95	197.51
Cerebellum Clontech	6.66	0.00	3.33	2.17	23.04	76.73
Cervix	11.99	12.30	12.15	2.42	20.66	250.93
Colon	55.51	211.32	133.42	2.71	18.45	2461.53
Endometrium	0.00	0.00	0.00	0.73	68.21	0.00
Esophagus	11.75	30.29	21.02	1.37	36.50	767.15
Heart Clontech	0.00	0.00	0.00	1.32	37.88	0.00
Hypothalamus	0.00	0.00	0.00	0.32	155.28	0.00
Ileum	40.37	42.85	41.61	2.58	19.38	806.40
Jejunum	200.19	263.82	232.01	6.60	7.58	1757.61
Kidney	18.38	34.53	26.46	2.12	23.58	623.94
Liver	11.00	17.20	14.10	1.50	33.33	470.00
Fetal Liver Clontech	150.74	123.93	137.34	10.40	4.81	660.26
Lung	82.73	77.24	79.99	2.57	19.46	1556.13
Mammary Gland	161.37	155.19	158.28	13.00	3.85	608.77
Clontech
Myometrium	5.79	9.38	7.59	2.34	21.37	162.07
Omentum	36.14	46.80	41.47	3.94	12.69	526.27
Ovary	59.25	44.29	51.77	4.34	11.52	596.43
Pancreas	6.29	6.70	6.50	0.81	61.80	401.42
Head of Pancreas	0.00	26.25	13.13	1.57	31.85	417.99
Parotid Gland	8.77	52.96	30.87	5.48	9.12	281.61
Placenta Clontech	4.11	0.00	2.06	5.26	9.51	19.53
Prostate	100.91	49.99	75.45	3.00	16.67	1257.50
Rectum	180.24	305.61	242.93	1.23	40.65	9875.00
Salivary Gland Clontech	49.36	70.01	59.69	7.31	6.84	408.24
Skeletal Muscle	0.00	0.00	0.00	1.26	39.68	0.00
Clontech
Skin	18.00	3.22	10.61	1.21	41.32	438.43
Small Intestine Clontech	3.90	2.55	3.23	0.98	51.07	164.71
Spleen	9.67	5.60	7.64	4.92	10.16	77.59
Stomach	32.34	83.60	57.97	2.73	18.32	1061.72
Testis Clontech	3.53	0.00	1.77	0.57	87.87	155.10
Thymus Clontech	73.66	60.02	66.84	9.89	5.06	337.92
Thyroid	15.87	12.31	14.09	2.77	18.05	254.33
Trachea Clontech	98.68	187.11	142.90	9.71	5.15	735.81
Urinary Bladder	118.92	101.91	110.42	5.47	9.14	1009.28
Uterus	9.03	24.21	16.62	5.34	9.36	155.62
			copies of
	Reg		mRNA
	number	Mean	detected/50 ng		Fold Change in
Sample	(GSK	GOI	total		Disease
SBh385630.antiinflam	identifier)	copies	RNA	Sample	Population
colon normal GW98-167	21941	6479.77	12959.54	colon normal
colon tumor GW98-166	21940	7824.02	15648.04	colon tumor	1.207453351
colon normal GW98-178	22080	343.81	687.62	colon normal
colon tumor GW98-177	22060	3011.93	6023.86	colon tumor	8.760449085
colon normal GW98-561	23514	5457.38	10914.76	colon normal
colon tumor GW98-560	23513	4017.14	8034.28	colon tumor	−1.358523726
colon normal GW98-894	24691	14903.68	29807.36	colon normal
colon tumor GW98-893	24690	4814.19	9628.38	colon tumor	−3.095781429
lung normal GW98-3	20742	3731.84	7463.68	lung normal
lung tumor GW98-2	20741	719.6	1439.20	lung tumor	−5.185992218
lung normal GW97-179	20677	1090.56	2181.12	lung normal
lung tumor GW97-178	20676	6187.22	12374.44	lung tumor	5.673433832
lung normal GW98-165	21922	8416.82	16833.64	lung normal
lung tumor GW98-164	21921	4405.14	8810.28	lung tumor	−1.910681613
lung normal GW98-282	22584	2033.26	4066.52	lung normal
lung tumor GW98-281	22583	1785.69	3571.38	lung tumor	−1.138641086
breast normal GW00-392	28750	1583.49	1583.49	breast
				normal
breast tumor GW00-391	28746	1334.89	2669.78	breast tumor	1.686010016
breast normal GW00-413	28798	1225.92	1225.92	breast
				normal
breast tumor GW00-412	28797	1213.71	2427.42	breast tumor	1.980080266
breast normal GW00-	27592-95	862.26	862.26	breast
235:238				normal
breast tumor GW00-	27588-91	1766.08	1766.08	breast tumor	2.048198919
231:234
breast normal GW98-621	23656	1420.57	2841.14	breast
				normal
breast tumor GW98-620	23655	760.05	1520.10	breast tumor	−1.869048089
brain normal BB99-542	25507	679.48	1358.96	brain normal
brain normal BB99-406	25509	423.69	847.38	brain normal
brain normal BB99-904	25546	401.34	802.68	brain normal
brain stage 5 ALZ BB99-	25502	264.51	529.02	brain stage 5	−1.895971167
874				ALZ
brain stage 5 ALZ BB99-	25503	648.88	1297.76	brain stage 5	1.293869765
887				ALZ
brain stage 5 ALZ BB99-	25504	234.97	469.94	brain stage 5	−2.134329205
862				ALZ
brain stage 5 ALZ BB99-	25542	404.55	809.10	brain stage 5	−1.239657232
927				ALZ
CT lung KC	normal	6620.85	13241.70	CT lung
lung 26 KC	normal	320.43	320.43	lung 26
lung 27 KC	normal	164.59	164.59	lung 27
lung 24 KC	COPD	141.57	141.57	lung 24	−25.25392032
lung 28 KC	COPD	323.8	323.80	lung 28	−11.04137585
lung 23 KC	COPD	363.35	363.35	lung 23	−9.839541764
lung 25 KC	COPD	574.07	574.07	lung 25
asthmatic lung	29321	6073.99	6073.99	asthmatic	1.698924325
ODO3112				lung
asthmatic lung	29323	4568.41	9136.82	asthmatic	2.555612662
ODO3433				lung
asthmatic lung	29322	17389.11	34778.22	asthmatic	9.727636026
ODO3397				lung
asthmatic lung	29325	4719.27	9438.54	asthmatic	2.640005203
ODO4928				lung
endo cells KC	control	0	0.00	endo cells
endo VEGF KC		0	0.00	endo VEGF	0
endo bFGF KC		0	0.00	endo bFGF	0
heart Clontech	normal	10.63	21.26	heart
heart (T-1) ischemic	29417	599.01	1198.02	heart T-1	56.3508937
heart (T-14) non-	29422	666.41	1332.82	heart T-14	62.69143932
obstructive DCM
heart (T-3399) DCM	29426	142.85	285.70	heart T-3399	13.43838194
adenoid GW99-269	26162	1138	2276.00	adenoid
tonsil GW98-280	22582	561.57	1123.14	tonsil
T cells PC00314	28453	736.27	1472.54	T cells
PBMNC KC		0	0.00	PBMNC
monocyte KC		30.38	60.76	monocyte
B cells PG00665	28455	204.15	408.30	B cells
dendritic cells 28441		57.66	115.32	dendritic
				cells
neutrophils	28440	13.3	13.30	neutrophils
eosinophils	28446	5.71	11.42	eosinophils
BM unstim KC		0	0.00	BM unstim
BM stim KC		50.38	50.38	BM stim	50.38
osteo dif KC		8.62	8.62	osteo dif
osteo undif KC		0	0.00	osteo undif	−8.62
chondrocytes		14.98	37.45	chondrocytes
OA Synovium IP12/01	29462	134.63	134.63	OA
				Synovium
OA Synovium NP10/01	29461	73.89	147.78	OA
				Synovium
OA Synovium NP57/00	28464	106.98	213.96	OA
				Synovium
RA Synovium NP03/01	28466	26.59	53.18	RA
				Synovium
RA Synovium NP71/00	28467	60.88	121.76	RA
				Synovium
RA Synovium NP45/00	28475	60.81	121.62	RA
				Synovium
OA bone (biobank)	29217	98.18	98.18	OA bone
				(biobank)
OA bone Sample 1	J. Emory	78.3	156.60	OA bone
OA bone Sample 2	J. Emory	107.7	215.40	OA bone
Cartilage (pool)	Normal	72.21	144.42	Cartilage
				(pool)
Cartilage (pool)	OA	48.61	97.22	Cartilage	−1.485496811
				(pool)
PBL unifected	28441	30.22	60.44	PBL
				unifected
PBL HIV IIIB	28442	21.89	43.78	PBL HIV	−1.380539059
				IIIB
MRC5 uninfected	29158	10.74	21.48	MRC5
(100%)				uninfected
				(100%)
MRC5 HSV strain F	29178	171.23	342.46	MRC5 HSV	15.94320298
				strain F
W12 cells	29179	1143.85	2287.70	W12 cells
Keratinocytes	29180	388.06	776.12	Keratinocytes

[0142]

Gene Name SBh385630.antiinflam
                  Fold Change in Disease
                  Population Relative to
Disease tissues   Normal
colon tumor       1.21
colon tumor       8.76
colon tumor       −1.36
colon tumor       −3.10
lung tumor        −5.19
lung tumor        5.67
lung tumor        −1.91
lung tumor        −1.14
breast tumor      1.69
breast tumor      1.98
breast tumor      2.05
breast tumor      −1.87
brain stage 5 ALZ −1.90
brain stage 5 ALZ 1.29
brain stage 5 ALZ −2.13
brain stage 5 ALZ −1.24
lung 24           −25.25
lung 28           −11.04
lung 23           −9.84
asthmatic lung    1.70
asthmatic lung    2.56
asthmatic lung    9.73
asthmatic lung    2.64
endo VEGF         0.00
endo bFGF         0.00
heart T-1         56.35
heart T-14        62.69
heart T-3399      13.44
BM stim           50.38
osteo undif       −8.62
Cartilage (pool)  −1.49
PBL HIV IIIB      −1.38
MRC5 HSV strain F 15.94

[0143] Gene Name sbg471005nAChR

[0144] Expressed in immune cells with corroborating expression in OA and RA synovium suggesting a role in this disease.

[0145] High expression in whole brain but not present in cortex, cerebellum, or hypothalamus suggesting localized brain expression.

						copies
						of
						mRNA
						detected/
	Mean GOI	Mean GOI	Average	18S	50 ng/18S	50 ng
Sample	copies	copies	GOI	rRNA	rRNA	total
sbg471005nAChR	(sample 1)	(sample 2)	Copies	(ng)	(ng)	RNA
Subcutaneous	32.42	2.90	17.66	3.06	16.34	288.56
Adipocytes Zenbio
Subcutaneous Adipose	0.00	0.00	0.00	0.96	52.36	0.00
Zenbio
Adrenal Gland Clontech	0.00	0.00	0.00	0.61	81.97	0.00
Whole Brain Clontech	1606.00	1058.07	1332.04	7.24	6.91	9199.14
Fetal Brain Clontech	0.00	6.34	3.17	0.48	103.95	329.52
Cerebellum Clontech	10.65	0.00	5.33	2.17	23.04	122.70
Cervix	0.00	0.00	0.00	2.42	20.66	0.00
Colon	0.00	0.00	0.00	2.71	18.45	0.00
Endometrium	0.00	0.00	0.00	0.73	68.21	0.00
Esophagus	0.00	2.52	1.26	1.37	36.50	45.99
Heart Clontech	4.05	0.00	2.03	1.32	37.88	76.70
Hypothalamus	2.24	0.00	1.12	0.32	155.28	173.91
Ileum	0.00	0.00	0.00	2.58	19.38	0.00
Jejunum	20.32	41.44	30.88	6.60	7.58	233.94
Kidney	14.56	0.00	7.28	2.12	23.58	171.70
Liver	3.55	10.72	7.14	1.50	33.33	237.83
Fetal Liver Clontech	127.95	116.81	122.38	10.40	4.81	588.37
Lung	12.79	0.00	6.40	2.57	19.46	124.42
Mammary Gland	30.53	24.12	27.33	13.00	3.85	105.10
Clontech
Myometrium	0.00	7.10	3.55	2.34	21.37	75.85
Omentum	8.15	0.00	4.08	3.94	12.69	51.71
Ovary	18.27	7.02	12.65	4.34	11.52	145.68
Pancreas	0.00	0.00	0.00	0.81	61.80	0.00
Head of Pancreas	0.00	0.00	0.00	1.57	31.85	0.00
Parotid Gland	0.00	0.00	0.00	5.48	9.12	0.00
Placenta Clontech	9.17	0.00	4.59	5.26	9.51	43.58
Prostate	0.00	1.35	0.68	3.00	16.67	11.25
Rectum	0.00	0.00	0.00	1.23	40.65	0.00
Salivary Gland	0.00	11.84	5.92	7.31	6.84	40.49
Clontech
Skeletal Muscle	6.09	7.36	6.73	1.26	39.68	266.87
Clontech
Skin	0.00	0.00	0.00	1.21	41.32	0.00
Small Intestine	0.00	0.00	0.00	0.98	51.07	0.00
Clontech
Spleen	5.20	7.36	6.28	4.92	10.16	63.82
Stomach	12.85	6.38	9.62	2.73	18.32	176.10
Testis Clontech	0.00	2.25	1.13	0.57	87.87	98.86
Thymus Clontech	177.85	168.23	173.04	9.89	5.06	874.82
Thyroid	6.44	0.00	3.22	2.77	18.05	58.12
Trachea Clontech	5.07	0.00	2.54	9.71	5.15	13.05
Urinary Bladder	0.00	0.00	0.00	5.47	9.14	0.00
Uterus	29.20	10.39	19.80	5.34	9.36	185.35
			copies of
	Reg		mRNA
	number	Mean	detected/50 ng		Fold Change
Sample	(GSK	GOI	total		in Disease
sbg471005nAChR	identifier)	copies	RNA	Sample	Population
colon normal GW98-167	21941	1530.09	3060.18	colon normal
colon tumor GW98-166	21940	617.15	1234.30	colon tumor	−2.479283805
colon normal GW98-178	22080	406.03	812.06	colon normal
colon tumor GW98-177	22060	1231.53	2463.06	colon tumor	3.033101002
colon normal GW98-561	23514	844.37	1688.74	colon normal
colon tumor GW98-560	23513	633.99	1267.98	colon tumor	−1.331834887
colon normal GW98-894	24691	1130.51	2261.02	colon normal
colon tumor GW98-893	24690	721.29	1442.58	colon tumor	−1.567344619
lung normal GW98-3	20742	2433.65	4867.30	lung normal
lung tumor GW98-2	20741	334.04	668.08	lung tumor	−7.28550473
lung normal GW97-179	20677	823.51	1647.02	lung normal
lung tumor GW97-178	20676	1492	2984.00	lung tumor	1.811756991
lung normal GW98-165	21922	829.65	1659.30	lung normal
lung tumor GW98-164	21921	595.31	1190.62	lung tumor	−1.393643648
lung normal GW98-282	22584	357.69	715.38	lung normal
lung tumor GW98-281	22583	256.76	513.52	lung tumor	−1.393090824
breast normal GW00-392	28750	357.44	357.44	breast
				normal
breast tumor GW00-391	28746	280.98	561.96	breast tumor	1.572179946
breast normal GW00-413	28798	286.18	286.18	breast
				normal
breast tumor GW00-412	28797	195.5	391.00	breast tumor	1.366272975
breast normal GW00-	27592-95	161.68	161.68	breast
235:238				normal
breast tumor GW00-	27588-91	217.83	217.83	breast tumor	1.347290945
231:234
breast normal GW98-621	23656	531.53	1063.06	breast
				normal
breast tumor GW98-620	23655	556.17	1112.34	breast tumor	1.046356744
brain normal BB99-542	25507	143.72	287.44	brain normal
brain normal BB99-406	25509	569.17	1138.34	brain normal
brain normal BB99-904	25546	106.85	213.70	brain normal
brain stage 5 ALZ BB99-	25502	286.37	572.74	brain stage 5	1.048027423
874				ALZ
brain stage 5 ALZ BB99-	25503	746.74	1493.48	brain stage 5	2.732842121
887				ALZ
brain stage 5 ALZ BB99-	25504	382.97	765.94	brain stage 5	1.401554151
862				ALZ
brain stage 5 ALZ BB99-	25542	367.49	734.98	brain stage 5	1.344902042
927				ALZ
CT lung KC	normal	175.41	350.82	CT lung
lung 26 KC	normal	20.66	20.66	lung 26
lung 27 KC	normal	13.06	13.06	lung 27
lung 24 KC	COPD	15.89	15.89	lung 24	−6.182662052
lung 28 KC	COPD	7.34	7.34	lung 28	−13.38453678
lung 23 KC	COPD	22.3	22.30	lung 23	−4.405493274
lung 25 KC	COPD	8.43	8.43	lung 25
asthmatic lung	29321	264.47	264.47	asthmatic	2.692012113
ODO3112				lung
asthmatic lung	29323	442.3	884.60	asthmatic	9.004249688
ODO3433				lung
asthmatic lung	29322	670.04	1340.08	asthmatic	13.64053236
ODO3397				lung
asthmatic lung	29325	414.13	828.26	asthmatic	8.430770797
ODO4928				lung
endo cells KC	control	66.94	66.94	endo cells
endo VEGF KC		18.49	18.49	endo VEGF	−3.620335316
endo bFGF KC		15.93	15.93	endo bFGF	−4.202134338
heart Clontech	normal	180.76	361.52	heart
heart (T-1) ischemic	29417	161.9	323.80	heart T-1	−1.116491662
heart (T-14) non-	29422	141.03	282.06	heart T-14	−1.281713111
obstructive DCM
heart (T-3399) DCM	29426	321.32	642.64	heart T-3399	1.777605665
adenoid GW99-269	26162	193.61	387.22	adenoid
tonsil GW98-280	22582	625.4	1250.80	tonsil
T cells PC00314	28453	140.44	280.88	T cells
PBMNC KC		0	0.00	PBMNC
monocyte KC		0	0.00	monocyte
B cells PC00665	28455	476.72	953.44	B cells
dendritic cells 28441		205.79	411.58	dendritic
				cells
neutrophils	28440	1366.99	1366.99	neutrophils
eosinophils	28446	316.57	633.14	eosinophils
BM unstim KC		29.41	29.41	BM unstim
BM stim KC		46.03	46.03	BM stim	1.565113907
osteo dif KC		17.47	17.47	osteo dif
osteo undif KC		1.87	1.87	osteo undif	−9.342245989
chondrocytes		735.88	1839.70	chondrocytes
OA Synovium IP12/01	29462	686.8	686.80	OA
				Synovium
OA Synovium NP10/01	29461	4887.16	9774.32	OA
				Synovium
OA Synovium NP57/00	28464	721.49	1442.98	OA
				Synovium
RA Synovium NP03/01	28466	383.33	766.66	RA
				Synovium
RA Synovium NP71/00	28467	780.94	1561.88	RA
				Synovium
RA Synovium NP45/00	28475	543.62	1087.24	RA
				Synovium
OA bone (biobank)	29217	780.12	780.12	OA bone
				(biobank)
OA bone Sample 1	J. Emory	361.65	723.30	OA bone
OA bone Sample 2	J. Emory	197.57	395.14	OA bone
Cartilage (pool)	Normal	220.7	441.40	Cartilage
				(pool)
Cartilage (pool)	OA	75.52	151.04	Cartilage	−2.922404661
				(pool)
PBL unifected	28441	1745.81	3491.62	PBL
				unifected
PBL HIV IIIB	28442	832.4	1664.80	PBL HIV	−2.097321
				IIIB
MRC5 uninfected	29158	147.92	295.84	MRC5
(100%)				uninfected
				(100%)
MRC5 HSV strain F	29178	146	292.00	MRC5 HSV	−1.013150685
				strain F
W12 cells	29179	304.27	608.54	W12 cells
Keratinocytes	29180	139.44	278.88	Keratinocytes

[0146]

Gene Name sbg471005nAChR
                  Fold Change in Disease
                  Population Relative to
Disease tissues   Normal
colon tumor       −2.48
colon tumor       3.03
colon tumor       −1.33
colon tumor       −1.57
lung tumor        −7.29
lung tumor        1.81
lung tumor        −1.39
lung tumor        −1.39
breast tumor      1.57
breast tumor      1.37
breast tumor      1.35
breast tumor      1.05
brain stage 5 ALZ 1.05
brain stage 5 ALZ 2.73
brain stage 5 ALZ 1.40
brain stage 5 ALZ 1.34
lung 24           −6.18
lung 28           −13.38
lung 23           −4.41
asthmatic lung    2.69
asthmatic lung    9.00
asthmatic lung    13.64
asthmatic lung    8.43
endo VEGF         −3.62
endo bFGF         −4.20
heart T-1         −1.12
heart T-14        −1.28
heart T-3399      1.78
BM stim           1.57
osteo undif       −9.34
Cartilage (pool)  −2.92
PBL HIV IIIB      −2.10
MRC5 HSV strain F −1.01

[0147] Gene Name sbg442445PROa

[0148] Strong expression in B-cells with expression in other immune cell types indicate function in immune system. Corroborating expression in RA and OA samples indicate role in disease. 2× increase in cells infected with HIV suggests possible marker in HIV infection. Expression in whole brain but not cortex or cerebellum suggests localized expression in brain.

						copies
						of
						mRNA
						detected/
	Mean GOI	Mean GOI	Average	18S	50 ng/18S	50 ng
Sample	copies	copies	GOI	rRNA	rRNA	total
sbg442445PROa	(sample 1)	(sample 2)	Copies	(ng)	(ng)	RNA
Subcutaneous	1.13	3.82	2.48	3.06	16.34	40.44
Adipocytes Zenbio
Subcutaneous Adipose	0.63	0	0.32	0.96	52.36	16.49
Zenbio
Adrenal Gland Clontech	0.64	0.74	0.69	0.61	81.97	56.56
Whole Brain Clontech	368.87	396.51	382.69	7.24	6.91	2642.89
Fetal Brain Clontech	1.57	2.5	2.04	0.48	103.95	211.54
Cerebellum Clontech	1.63	0	0.82	2.17	23.04	18.78
Cervix	4.57	5.6	5.09	2.42	20.66	105.06
Colon	18.13	7.38	12.76	2.71	18.45	235.33
Endometrium	4.23	0	2.12	0.73	68.21	144.27
Esophagus	6.85	12.66	9.76	1.37	36.50	356.02
Heart Clontech	12.83	1.44	7.14	1.32	37.88	270.27
Hypothalamus	0.58	7.26	3.92	0.32	155.28	608.70
Ileum	22.89	6.34	14.62	2.58	19.38	283.24
Jejunum	6.67	36.71	21.69	6.60	7.58	164.32
Kidney	2.82	6.28	4.55	2.12	23.58	107.31
Liver	11.21	1.24	6.23	1.50	33.33	207.50
Fetal Liver Clontech	118	135.81	126.91	10.40	4.81	610.12
Lung	13.95	37.87	25.91	2.57	19.46	504.09
Mammary Gland	15.77	11.19	13.48	13.00	3.85	51.85
Clontech
Myometriun	16.26	49.21	32.74	2.34	21.37	699.47
Omeatum	16.64	25.59	21.12	3.94	12.69	267.96
Ovary	4.98	7.48	6.23	4.34	11.52	71.77
Pancreas	1.23	0	0.62	0.81	61.80	38.01
Head of Pancreas	3.57	0	1.79	1.57	31.85	56.85
Parotid Gland	0.59	0	0.30	5.48	9.12	2.69
Placenta Clontech	2.67	2.75	2.71	5.26	9.51	25.76
Prostate	9.23	7.92	8.58	3.00	16.67	142.92
Rectum	2.62	4.28	3.45	1.23	40.65	140.24
Salivary Gland	1.02	14.59	7.81	7.31	6.84	53.39
Clontech
Skeletal Muscle	0	0.98	0.49	1.26	39.68	19.44
Clontech
Skin	2.72	0	1.36	1.21	41.32	56.20
Small Intestine	0.99	1	1.00	0.98	51.07	50.82
Clontech
Spleen	31.29	42.16	36.73	4.92	10.16	373.22
Stomach	15.74		7.87	2.73	18.32	144.14
Testis Clontech	4.63	2.77	3.70	0.57	87.87	325.13
Thymus Clontech	503.91	615.6	559.76	9.89	5.06	2829.90
Thyroid	0.75	10.38	5.57	2.77	18.05	100.45
Trachea Clontech	65.95	52.98	59.47	9.71	5.15	306.20
Urinary Bladder	9.1	3.76	6.43	5.47	9.14	58.78
Uterus	13.88	4.35	9.12	5.34	9.36	85.35
			copies of
	Reg		mRNA
	number	Mean	detected/50 ng		Fold Change
Sample	(GSK	GOI	total		in Disease
sbg442445PROa	identifier)	copies	RNA	Sample	Population
colon normal GW98-167	21941	392.89	785.78	colon normal
colon tumor GW98-166	21940	466.75	933.50	colon tumor	1.18799155
colon normal GW98-178	22080	113.54	227.08	colon normal
colon tumor GW98-177	22060	43.88	87.76	colon tumor	−2.587511395
colon normal GW98-561	23514	335.16	670.32	colon normal
colon tumor GW98-560	23513	173.85	347.70	colon tumor	−1.927868852
colon normal GW98-894	24691	288.76	577.52	colon normal
colon tumor GW98-893	24690	164.44	328.88	colon tumor	−1.756020433
lung normal GW98-3	20742	2119.16	4238.32	lung normal
lung tumor GW98-2	20741	33.63	67.26	lung tumor	−63.01397562
lung normal GW97-179	20677	1213.42	2426.84	lung normal
lung tumor GW97-178	20676	2011.79	4023.58	lung tumor	1.657950256
lung normal GW98-165	21922	2088.93	4177.86	lung normal
lung tumor GW98-164	21921	862.54	1725.08	lung tumor	−2.421835509
lung normal GW98-282	22584	499.54	999.08	lung normal
lung tumor GW98-281	22583	946.36	1892.72	lung tumor	1.894462906
breast normal GW00-392	28750	208.96	208.96	breast normal
breast tumor GW00-391	28746	259.34	518.68	breast tumor	2.48219755
breast normal GW00-413	28798	65.02	65.02	breast normal
breast tumor GW00-412	28797	493.02	986.04	breast tumor	15.16517994
breast normal GW00-	27592-95	24.18	24.18	breast normal
235:238
breast tumor GW00-	27588-91	126.63	126.63	breast tumor	5.236972705
231:234
breast normal GW98-621	23656	536.09	1072.18	breast normal
breast tumor GW98-620	23655	203.7	407.40	breast tumor	−2.631762396
brain normal BB99-542	25507	88.47	176.94	brain normal
brain normal BB99-406	25509	147.87	295.74	brain normal
brain normal BB99-904	25546	35.13	70.26	brain normal
brain stage 5 ALZ BB99-	25502	75.02	150.04	brain stage 5	−1.206211677
874				ALZ
brain stage 5 ALZ BB99-	25503	189	378.00	brain stage 5	2.088628578
887				ALZ
brain stage 5 ALZ BB99-	25504	131.38	262.76	brain stage 5	1.451873135
862				ALZ
brain stage 5 ALZ BB99-	25542	36.77	73.54	brain stage 5	−2.46097362
927				ALZ
CT lung KC	normal	1441.16	2882.32	CT lung
lung 26 KC	normal	69.7	69.70	lung 26
lung 27 KC	normal	59.95	59.95	lung 27
lung 24 KC	COPD	5.33	5.33	lung 24	−142.0727017
lung 28 KC	COPD	30.24	30.24	lung 28	−25.04125331
lung 23 KC	COPD	52.96	52.96	lung 23	−14.29847998
lung 25 KC	COPD	17.02	17.02	lung 25
asthmatic lung	29321	309.94	309.94	asthmatic	−2.44320675
ODO3112				lung
asthmatic lung	29323	532.32	1064.64	asthmatic	1.405933991
ODO3433				lung
asthmatic lung	29322	1159.05	2318.10	asthmatic	3.061218426
ODO3397				lung
asthmatic lung	29325	873.73	1747.46	asthmatic	2.307647103
ODO4928				lung
endo cells KC	control	0	0.00	endo cells
endo VEGF KC		0.93	0.93	endo VEGF	0.93
endo bFGF KC		5.16	5.16	endo bFGF	5.16
heart Clontech	normal	43.01	86.02	heart
heart (T-1) ischemic	29417	81.55	163.10	heart T-1	1.896070681
heart (T-14) non-	29422	51.64	103.28	heart T-14	1.200651011
obstructive DCM
heart (T-3399) DCM	29426	90.27	180.54	heart T-3399	2.098814229
adenoid GW99-269	26162	982.05	1964.10	adenoid
tonsil GW98-280	22582	3981.71	7963.42	tonsil
T cells PC00314	28453	265.95	531.90	T cells
PBMNC KC		40.89	40.89	PBMNC
monocyte KC		62.92	125.84	monocyte
B cells PC00665	28455	9045.58	18091.16	B cells
dendritic cells 28441		267.47	534.94	dendritic cells
neutrophils	28440	1212.1	1212.10	neutrophils
eosinophils	28446	1563.76	3127.52	eosinophils
BM unstim KC		56.55	56.55	BM unstim
BM stim KC		27.4	27.40	BM stim	−2.063868613
osteo dif KC		0	0.00	osteo dif
osteo undif KC		0	0.00	osteo undif	0
chondrocytes		0.92	2.30	chondrocytes
OA Synovium IP12/01	29462	524.44	524.44	OA
				Synovium
OA Synovium NP10/01	29461	191.8	383.60	OA
				Synovium
OA Synovium NP57/00	28464	461.09	922.18	OA
				Synovium
RA Synovium NP03/01	28466	484.63	969.26	RA Synovium
RA Synovium NP71/00	28467	698.08	1396.16	RA Synovium
RA Synovium NP45/00	28475	1034.78	2069.56	RA Synovium
OA bone (biobank)	29217	547.68	547.68	OA bone
				(biobank)
OA bone Sample 1	J. Emory	286.6	573.20	OA bone
OA bone Sample 2	J. Emory	604.86	1209.72	OA bone
Cartilage (pool)	Normal	224.68	449.36	Cartilage
				(pool)
Cartilage (pool)	OA	113.78	227.56	Cartilage	−1.974687994
				(pool)
PBL unifected	28441	966.68	1933.36	PBL
				unifected
PBL HIV IIIB	28442	1353.87	2707.74	PBL HIV	1.400535855
				IIIB
MRC5 uninfected	29158	1.28	2.56	MRC5
(100%)				uninfected
				(100%)
MRC5 HSV strain F	29178	34.07	68.14	MRC5 HSV	26.6171875
				strain F
W12 cells	29179	3.55	7.10	W12cells
Keratinocytes	29180	5.64	11.28	Keratinocytes

[0149]

Gene Name sbg442445PROa
                  Fold Change in Disease
                  Population Relative to
Disease tissues   Normal
colon tumor       1.19
colon tumor       −2.59
colon tumor       −1.93
colon tumor       −1.76
lung tumor        −63.01
lung tumor        1.66
lung tumor        −2.42
lung tumor        1.89
breast tumor      2.48
breast tumor      15.17
breast tumor      5.24
breast tumor      −2.63
brain stage 5 ALZ −1.21
brain stage 5 ALZ 2.09
brain stage 5 ALZ 1.45
brain stage 5 ALZ −2.46
lung 24           −142.07
lung 28           −25.04
lung 23           −14.30
asthmatic lung    −2.44
asthmatic lung    1.41
asthmatic lung    3.06
asthmatic lung    2.31
endo VEGF         0.93
endo bFGF         5.16
heart T-1         1.90
heart T-14        1.20
heart T-3399      2.10
BM stim           −2.06
osteo undif       0.00
Cartilage (pool)  −1.97
PBL HIV IIIB      1.40
MRC5 HSV strain F 26.62

[0150] Gene Name sbg456548CytoRa

[0151] Strongly expressed in adenoid/tonsils and dendritic cells. Overexpressed in stimulated bone marrow. Taken together, these data suggest a role in immune function. Expression in GI tract suggests potential role in diseases of the GI system like IBD, Chron's, etc.

						copies of
						mRNA
						detected/
	Mean GOI	Mean GOI	Average	18S	50 ng/18S	50 ng
Sample	copies	copies	GOI	rRNA	rRNA	total
sbg456548CytoRa	(sample 1)	(sample 2)	Copies	(ng)	(ng)	RNA
Subcutaneous	0.00	5.06	2.53	3.06	16.34	41.34
Adipocytes Zenbio
Subcutaneous Adipose	0.00	0.00	0.00	0.96	52.36	0.00
Zenbio
Adrenal Gland Clontech	0.00	0.00	0.00	0.61	81.97	0.00
Whole Brain Clontech	0.00	0.00	0.00	7.24	6.91	0.00
Fetal Brain Clontech	0.00	0.00	0.00	0.48	103.95	0.00
Cerebellum Clontech	0.00	0.00	0.00	2.17	23.04	0.00
Cervix	0.00	7.86	3.93	2.42	20.66	81.20
Colon	9.12	37.61	23.37	2.71	18.45	431.09
Endometrium	0.00	0.00	0.00	0.73	68.21	0.00
Esophagus	0.00	0.00	0.00	1.37	36.50	0.00
Heart Clontech	0.00	0.00	0.00	1.32	37.88	0.00
Hypothalamus	0.00	0.00	0.00	0.32	155.28	0.00
Ileum	not done	39.63	39.63	2.58	19.38	768.02
Jejunum	9.16	33.67	21.42	6.60	7.58	162.23
Kidney	0.00	0.00	0.00	2.12	23.58	0.00
Liver	0.00	13.75	6.88	1.50	33.33	229.17
Fetal Liver Clontech	0.00	0.00	0.00	10.40	4.81	0.00
Lung	0.00	0.00	0.00	2.57	19.46	0.00
Mammary Gland	136.73	106.34	121.54	13.00	3.85	467.44
Clontech
Myometrium	27.33	17.56	22.45	2.34	21.37	479.59
Omentum	0.00	12.61	6.31	3.94	12.69	80.01
Ovary	16.46	17.90	17.18	4.34	11.52	197.93
Pancreas	0.00	0.00	0.00	0.81	61.80	0.00
Head of Pancreas	0.00	0.00	0.00	1.57	31.85	0.00
Parotid Gland	21.25	23.72	22.49	5.48	9.12	205.16
Placenta Clontech	101.11	73.40	87.26	5.26	9.51	829.42
Prostate	8.55	0.00	4.28	3.00	16.67	71.25
Rectum	0.00	0.00	0.00	1.23	40.65	0.00
Salivary Gland	0.00	0.00	0.00	7.31	6.84	0.00
Clontech
Skeletal Muscle	0.00	0.00	0.00	1.26	39.68	0.00
Clontech
Skin	0.00	0.00	0.00	1.21	41.32	0.00
Small Intestine	0.00	0.00	0.00	0.98	51.07	0.00
Clontech
Spleen	31.60	14.66	23.13	4.92	10.16	235.06
Stomach	0.00	7.01	3.51	2.73	18.32	64.19
Testis Clontech	0.00	0.00	0.00	0.57	87.87	0.00
Thymus Clontech	51.70	103.21	77.46	9.89	5.06	391.58
Thyroid	0.00	0.00	0.00	2.77	18.05	0.00
Trachea Clontech	0.00	0.00	0.00	9.71	5.15	0.00
Urinary Bladder	0.00	7.29	3.65	5.47	9.14	33.32
Uterus	5.98	21.02	13.50	5.34	9.36	126.40
			copies of
	Reg		mRNA
	number	Mean	detected/50 ng		Fold Change in
Sample	(GSK	GOI	total		Disease
sbg456548CytoRa	identifier)	copies	RNA	Sample	Population
colon normal GW98-167	21941	54.19	108.38	colon normal
colon tumor GW98-166	21940	242.87	485.74	colon tumor	4.481823215
colon normal GW98-178	22080	24.61	49.22	colon normal
colon tumor GW98-177	22060	17.37	34.74	colon tumor	−1.416810593
colon normal GW98-561	23514	120.13	240.26	colon normal
colon tumor GW98-560	23513	43.05	86.10	colon tumor	−2.79047619
colon normal GW98-894	24691	81.35	162.70	colon normal
colon tumor GW98-893	24690	16.94	33.88	colon tumor	−4.802243211
lung normal GW98-3	20742	12.83	25.66	lung normal
lung tumor GW98-2	20741	94.41	188.82	lung tumor	7.358534684
lung normal GW97-179	20677	519.7	1039.40	lung normal
lung tumor GW97-178	20676	46.83	93.66	lung tumor	−11.09758702
lung normal GW98-165	21922	7.95	15.90	lung normal
lung tumor GW98-164	21921	237.54	475.08	lung tumor	29.87924528
lung normal GW98-282	22584	251.04	502.08	lung normal
lung tumor GW98-281	22583	28.16	56.32	lung tumor	−8.914772727
breast normal GW00-392	28750	138.99	138.99	breast
				normal
breast tumor GW00-391	28746	147.66	295.32	breast tumor	2.124757177
breast normal GW00-413	28798	30.39	30.39	breast
				normal
breast tumor GW00-412	28797	37.64	75.28	breast tumor	2.477130635
breast normal GW00-	27592-95	218.09	218.09	breast
235:238				normal
breast tumor GW00-	27588-91	14.68	14.68	breast tumor	−14.85626703
231:234
breast normal GW98-621	23656	1888.3	3776.60	breast
				normal
breast tumor GW98-620	23655	877.2	1754.40	breast tumor	−2.152644779
brain normal BB99-542	25507	0	0.00	brain normal
brain normal BB99-406	25509	0	0.00	brain normal
brain normal BB99-904	25546	0	0.00	brain normal
brain stage 5 ALZ BB99-	25502	0	0.00	brain stage 5	0
874				ALZ
brain stage 5 ALZ BB99-	25503	7.32	14.64	brain stage 5	14.64
887				ALZ
brain stage 5 ALZ BB99-	25504	0	0.00	brain stage 5	0
862				ALZ
brain stage 5 ALZ BB99-	25542	0	0.00	brain stage 5	0
927				ALZ
CT lung KC	normal	10.31	20.62	CT lung
lung 26 KC	normal	49.79	49.79	lung 26
lung 27 KC	normal	4.11	4.11	lung 27
lung 24 KC	COPD	0.67	0.67	lung 24	−38.10074627
lung 28 KC	COPD	19.24	19.24	lung 28	−1.326793139
lung 23 KC	COPD	3.15	3.15	lung 23	−8.103968254
lung 25 KC	COPD	27.59	27.59	lung 25
asthmatic lung	29321	2.95	2.95	asthmatic	−8.653389831
ODO3112				lung
asthmatic lung	29323	9.86	19.72	asthmatic	−1.294497972
ODO3433				lung
asthmatic lung	29322	24.39	48.78	asthmatic	1.910880423
ODO3397				lung
asthmatic lung	29325	53.84	107.68	asthmatic	4.218196063
ODO4928				lung
endo cells KC	control	0	0.00	endo cells
endo VEGF KC		14.65	14.65	endo VEGF	14.65
endo bFGF KC		0	0.00	endo bFGF	0
heart Clontech	normal	0	0.00	heart
heart (T-1 ) ischemic	29417	21.18	42.36	heart T-1	42.36
heart (T-14) non-	29422	27.4	54.80	heart T-14	54.8
obstructive DCM
heart (T-3399) DCM	29426	93.27	186.54	heart T-3399	186.54
adenoid GW99-269	26162	579.69	1159.38	adenoid
tonsil GW98-280	22582	3780.08	7560.16	tonsil
T cells PG00314	28453	5.86	11.72	T cells
PBMNC KC		0	0.00	PBMNC
monocyte KC		0	0.00	monocyte
B cells PG00665	28455	19.6	39.20	B cells
dendritic cells 28441		580.67	1161.34	dendritic
				cells
neutrophils	28440	19.76	19.76	neutrophils
eosinophils	28446	15.12	30.24	eosinophils
BM unstim KC		0	0.00	BM unstim
BM stim KC		296.72	296.72	BM stim	296.72
osteo dif KC		0	0.00	osteo dif
osteo undif KC		0	0.00	osteo undif	0
chondrocytes		15.31	38.28	chondrocytes
OA Synovium IP12/01	29462	39.57	39.57	OA
				Synovium
OA Synovium NP10/01	29461	0	0.00	OA
				Synovium
OA Synovium NP57/00	28464	70.08	140.16	OA
				Synovium
RA Synovium NP03/01	28466	23.73	47.46	RA
				Synovium
RA Synovium NP71/00	28467	24.13	48.26	RA
				Synovium
RA Synovium NP45/00	28475	51.88	103.76	RA
				Synovium
OA bone (biobank)	29217	0	0.00	OA bone
				(biobank)
OA bone Sample 1	J. Emory	0	0.00	OA bone
OA bone Sample 2	J. Emory	5.45	10.90	OA bone
Cartilage (pool)	Normal	0	0.00	Cartilage
				(pool)
Cartilage (pool)	OA	0	0.00	Cartilage	0
				(pool)
PBL unifected	28441	76.67	153.34	PBL
				unifected
PBL HIV IIIB	28442	13.77	27.54	PBL HIV	−5.567901235
				IIIB
MRC5 uninfected	29158	0	0.00	MRC5
(100%)				uninfected
				(100%)
MRC5 HSV strain F	29178	0	0.00	MRC5 HSV	0
				strain F
W12 cells	29179	0	0.00	W12 cells
Keratinocytes	29180	0	0.00	Keratinocytes

[0152]

Gene Name sbg456548CytoRa
                Fold Change in Disease
                Population Relative to
Disease tissues Normal
colon tumor     4.48
colon tumor     −1.42
colon tumor     −2.79
colon tumor     −4.80
lung tumor      7.36

[0153] Gene Name sbg442358PROa

[0154] Expression in multiple immune cell types as well as stimulated bone marrow and thymus strongly suggests function in immune system. Overexpressed in breast tumors (1/4). Expression in RA and OA with corroborating expression in immune cells suggests role in these diseases. Overexpressed in heart disease suggesting role in CV diseases. Downregulated in HSV infected cells suggesting possible host cell factor.

						copies
						of
						mRNA
						detected/
	Mean GOI	Mean GOI	Average	18S	50 ng/18S	50 ng
Sample	copies	copies	GOI	rRNA	rRNA	total
sbg442358PROa	(sample 1)	(sample 2)	Copies	(ng)	(ng)	RNA
Subcutaneous	1.86	1.71	1.79	3.06	16.34	29.17
Adipocytes Zenbio
Subcutaneous Adipose	0.71	0.73	0.72	0.96	52.36	37.70
Zenbio
Adrenal Gland Clontech	3.45	1.89	2.67	0.61	81.97	218.85
Whole Brain Clontech	406.27	496.60	451.44	7.24	6.91	3117.65
Fetal Brain Clontech	3.82	1.68	2.75	0.48	103.95	285.86
Cerebellum Clontech	5.84	30.51	18.18	2.17	23.04	418.78
Cervix	2.50	0.48	1.49	2.42	20.66	30.79
Colon	18.45	18.77	18.61	2.71	18.45	343.36
Endometrium	4.93	0.30	2.62	0.73	68.21	178.38
Esophagus	8.97	6.99	7.98	1.37	36.50	291.24
Heart Clontech	5.26	16.53	10.90	1.32	37.88	412.69
Hypothalamus	2.10	2.41	2.26	0.32	155.28	350.16
Ileum	18.94	12.62	15.78	2.58	19.38	305.81
Jejunum	65.51	95.24	80.38	6.60	7.58	608.90
Kidney	2.60	3.81	3.21	2.12	23.58	75.59
Liver	7.19	7.05	7.12	1.50	33.33	237.33
Fetal Liver Clontech	1252.22	1363.06	1307.64	10.40	4.81	6286.73
Lung	27.57	6.97	17.27	2.57	19.46	335.99
Mammary Gland	79.83	72.99	76.41	13.00	3.85	293.88
Clontech
Myometrium	2.46	10.62	6.54	2.34	21.37	139.74
Omentum	10.40	3.27	6.84	3.94	12.69	86.74
Ovary	17.71	31.15	24.43	4.34	11.52	281.45
Pancreas	3.33	1.74	2.54	0.81	61.80	156.67
Head of Pancreas	3.82	6.17	5.00	1.57	31.85	159.08
Parotid Gland	22.77	22.54	22.66	5.48	9.12	206.71
Placenta Clontech	14.71	53.83	34.27	5.26	9.51	325.76
Prostate	16.71	19.39	18.05	3.00	16.67	300.83
Rectum	6.71	3.49	5.10	1.23	40.65	207.32
Salivary Gland	55.38	9.30	32.34	7.31	6.84	221.20
Clontech
Skeletal Muscle	3.79	4.16	3.98	1.26	39.68	157.74
Clontech
Skin	4.51	14.47	9.49	1.21	41.32	392.15
Small Intestine	8.12	7.87	8.00	0.98	51.07	408.32
Clontech
Spleen	14.88	17.12	16.00	4.92	10.16	162.60
Stomach	21.85	11.68	16.77	2.73	18.32	307.05
Testis Clontech	22.77	11.54	17.16	0.57	87.87	1507.47
Thymus Clontech	1990.82	1374.71	1682.77	9.89	5.06	8507.41
Thyroid	16.85	2.86	9.86	2.77	18.05	177.89
Trachea Clontech	29.69	82.85	56.27	9.71	5.15	289.75
Urinary Bladder	2.32	13.42	7.87	5.47	9.14	71.94
Uterus	8.86	11.18	10.02	5.34	9.36	93.82
			copies of
	Reg		mRNA
	number	Mean	detected/50 ng		Fold Change
Sample	(GSK	GOI	total		in Disease
sbg442358PROa	identifier)	copies	RNA	Sample	Population
colon normal GW98-167	21941	1232.32	2464.64	colon normal
colon tumor GW98-166	21940	2940.17	5880.34	colon tumor	2.385881914
colon normal GW98-178	22080	221.26	442.52	colon normal
colon tumor GW98-177	22060	709.52	1419.04	colon tumor	3.20672512
colon normal GW98-561	23514	985.52	1971.04	colon normal
colon tumor GW98-560	23513	829.67	1659.34	colon tumor	−1.18784577
colon normal GW98-894	24691	2738.17	5476.34	colon normal
colon tumor GW98-893	24690	3022.06	6044.12	colon tumor	1.103678734
lung normal GW98-3	20742	536.82	1073.64	lung normal
lung tumor GW98-2	20741	594.2	1188.40	lung tumor	1.106888715
lung normal GW97-179	20677	4382.61	8765.22	lung normal
lung tumor GW97-178	20676	359.07	718.14	lung tumor	−12.20544741
lung normal GW98-165	21922	622.06	1244.12	lung normal
lung tumor GW98-164	21921	1299.85	2599.70	lung tumor	2.089589429
lung normal GW98-282	22584	1782.09	3564.18	lung normal
lung tumor GW98-281	22583	470.51	941.02	lung tumor	−3.787570934
breast normal GW00-392	28750	429	429.00	breast normal
breast tumor GW00-391	28746	417.99	835.98	breast tumor	1.948671329
breast normal GW00-413	28798	16.03	16.03	breast normal
breast tumor GW00-412	28797	1048.11	2096.22	breast tumor	130.768559
breast normal GW00-	27592-95	2.17	2.17	breast normal
235:238
breast tumor GW00-	27588-91	69.91	69.91	breast tumor	32.21658986
231:234
breast normal GW98-621	23656	1037.08	2074.16	breast normal
breast tumor GW98-620	23655	1010.59	2021.18	breast tumor	−1.026212411
brain normal BB99-542	25507	299.28	598.56	brain normal
brain normal BB99-406	25509	250.85	501.70	brain normal
brain normal BB99-904	25546	97.7	195.40	brain normal
brain stage 5 ALZ BB99-	25502	125	250.00	brain stage 5	−1.727546667
874				ALZ
brain stage 5 ALZ BB99-	25503	850.01	1700.02	brain stage 5	3.936264143
887				ALZ
brain stage 5 ALZ BB99-	25504	347.91	695.82	brain stage 5	1.611117114
862				ALZ
brain stage 5 ALZ BB99-	25542	147.11	294.22	brain stage 5	−1.467903836
927				ALZ
CT lung KC	normal	130.37	260.74	CT lung
lung 26 KC	normal	159.19	159.19	lung 26
lung 27 KC	normal	0.49	0.49	lung 27
lung 24 KC	COPD	2.37	2.37	lung 24	−47.89873418
lung 28 KC	COPD	45.72	45.72	lung 28	−2.482939633
lung 23 KC	COPD	20.36	20.36	lung 23	−5.575638507
lung 25 KC	COPD	33.66	33.66	lung 25
asthmatic lung	29321	65.46	65.46	asthmatic	−1.734188818
ODO3112				lung
asthmatic lung	29323	532.42	1064.84	asthmatic	9.380197322
ODO3433				lung
asthmatic lung	29322	2865.67	5731.34	asthmatic	50.48749119
ODO3397				lung
asthmatic lung	29325	494.27	988.54	asthmatic	8.708069063
ODO4928				lung
endo cells KC	control	62.77	62.77	endo cells
endo VEGF KC		22.41	22.41	endo VEGF	−2.800981705
endo bFGF KC		33.16	33.16	endo bFGF	−1.892943305
heart Clontech	normal	74.18	148.36	heart
heart ( T-1 ) ischemic	29417	270.07	540.14	heart T-1	3.640738744
heart (T-14) non-	29422	680.12	1360.24	heart T-14	9.168509032
obstructive DCM
heart (T-3399) DCM	29426	414	828.00	heart T-3399	5.581019143
adenoid GW99-269	26162	781.46	1562.92	adenoid
tonsil GW98-280	22582	2279.13	4558.26	tonsil
T cells PC00314	28453	1129.27	2258.54	T cells
PBMNC KC		27.98	27.98	PBMNC
monocyte KC		3.55	7.10	monocyte
B cells PC00665	28455	872.58	1745.16	B cells
dendritic cells 28441		1055.22	2110.44	dendritic cells
neutrophils	28440	740.39	740.39	neutrophils
eosinophils	28446	1081.83	2163.66	eosinophils
BM unstim KC		50.91	50.91	BM unstim
BM stim KC		391.11	391.11	BM stim	7.682380672
osteo dif KC		161.31	161.31	osteo dif
osteo undif KC		40.01	40.01	osteo undif	−4.031742064
chondrocytes		2250.59	5626.48	chondrocytes
OA Synovium IP12/01	29462	229.19	229.19	OA
				Synovium
OA Synovium NP10/01	29461	152.3	304.60	OA
				Synovium
OA Synovium NP57/00	28464	413.06	826.12	OA
				Synovium
RA Synovium NP03/01	28466	611.02	1222.04	RA Synovium
RA Synovium NP71/00	28467	385.94	771.88	RA Synovium
RA Synovium NP45/00	28475	1701.68	3403.36	RA Synovium
OA bone (biobank)	29217	225.69	225.69	OA bone
				(biobank)
OA bone Sample 1	J. Emory	306.63	613.26	OA bone
OA bone Sample 2	J. Emory	1811.32	3622.64	OA bone
Cartilage (pool)	Normal	384.44	768.88	Cartilage
				(pool)
Cartilage (pool)	OA	174.53	349.06	Cartilage	−2.202715865
				(pool)
PBL unifected	28441	9016.82	18033.64	PBL
				unifected
PBL HIV IIIB	28442	4331.76	8663.52	PBL HIV	−2.081560382
				IIIB
MRC5 uninfected	29158	2232.48	4464.96	MRC5
(100%)				uninfected
				(100%)
MRC5 HSV strain F	29178	419.67	839.34	MRC5 HSV	−5.319608264
				strain F
W12 cells	29179	3336.07	6672.14	W12 cells
Keratinocytes	29180	5568.91	11137.82	Keratinocytes

[0155]

Gene Name sbg442358PROa
                  Fold Change in Disease
                  Population Relative to
Disease tissues   Normal
colon tumor       2.39
colon tumor       3.21
colon tumor       −1.19
colon tumor       1.10
lung tumor        1.11
lung tumor        −12.21
lung tumor        2.09
lung tumor        −3.79
breast tumor      1.95
breast tumor      130.77
breast tumor      32.22
breast tumor      −1.03
brain stage 5 ALZ −1.73
brain stage 5 ALZ 3.94
brain stage 5 ALZ 1.61
brain stage 5 ALZ −1.47
lung 24           −47.90
lung 28           −2.48
lung 23           −5.58
asthmatic lung    −1.73
asthmatic lung    9.38
asthmatic lung    50.49
asthmatic lung    8.71
endo VEGF         −2.80
endo bFGF         −1.89
heart T-1         3.64
heart T-14        9.17
heart T-3399      5.58
BM stim           7.68
osteo undif       −4.03
Cartilage (pool)  −2.20
PBL HIV IIIB      −2.08
MRC5 HSV strain F −5.32

[0156]

TABLE V
Additional diseases based on mRNA expression in specific tissues
Tissue
Expression   Additional Diseases
Brain        Neurological and psychiatric diseases, including Alzheimers, parasupranuclear
             palsey, Huntington's disease, myotonic dystrophy, anorexia, depression,
             schizophrenia, headache, amnesias, anxiety disorders, sleep disorders, multiple
             sclerosis
Heart        Cardiovascular diseases, including congestive heart failure, dilated
             cardiomyopathy, cardiac arrhythmias, Hodgson's Disease, myocardial
             infarction, cardiac arrhythmias
Lung         Respiratory diseases, including asthma, Chronic Obstructive Pulmonary
             Disease, cystic fibrosis, acute bronchitis, adult respiratory distress syndrome
Liver        Dyslipidemia, hypercholesterolemia, hypertriglyceridemia, cirrhosis, hepatic
             encephalopatby, fatty hepatocirrhosis, viral and nonviral hepatitis, Type II
             Diabetes Mellitis, impaired glucose tolerance
Kidney       Renal diseases, including acute and chronic renal failure, acute tubular necrosis,
             cystinuria, Fanconi's Syndrome, glomerulonephritis, renal cell carcinoma,
             renovascular hypertension
Skeletal     Eulenburg's Disease, hypoglycemia, obesity, tendinitis, periodic paralyses,
muscle       malignant hyperthermia, paramyotonia congenita, myotonia congenita
Intestine    Gastrointestinal diseases, including Myotonia congenita, Ileus, Intestinal
             Obstruction, Tropical Sprue, Pseudomembranous Enterocolitis
Spleen/lymph Lymphangiectasia, hypersplenism, angiomas, ankylosing spondylitis, Hodgkin's
             Disease, macroglobulinemia, malignant lymphomas, rheumatoid arthritis
Placenta     Choriocarcinoma, hydatidiform mole, placenta previa
Testis       Testicular cancer, male reproductive diseases, including low testosterone and
             male infertility
Pancreas     Diabetic ketoacidosis, Type 1 & 2 diabetes, obesity, impaired glucose tolerance

[0157]

Claims

1. An isolated polypeptide selected from the group consisting of: (a) an isolated polypeptide encoded by a polynucleotide comprising a sequence set forth in Table I; (b) an isolated polypeptide comprising a polypeptide sequence set forth in Table I; and (c) a polypeptide sequence of a gene set forth in Table I.

2. An isolated polynucleotide selected from the group consisting of: (a) an isolated polynucleotide comprising a polynucleotide sequence set forth in Table I; (b) an isolated polynucleotide of a gene set forth in Table I; (c) an isolated polynucleotide comprising a polynucleotide sequence encoding a polypeptide set forth in Table I; (d) an isolated polynucleotide encoding a polypeptide set forth in Table I; (e) a polynucleotide which is an RNA equivalent of the polynucleotide of (a) to (d); or a polynucleotide sequence complementary to said isolated polynucleotide.

3. An expression vector comprising a polynucleotide capable of producing a polypeptide of claim 1 when said expression vector is present in a compatible host cell.

4. A process for producing a recombinant host cell which comprises the step of introducing an expression vector comprising a polynucleotide capable of producing a polypeptide of claim 1 into a cell such that the host cell, under appropriate culture conditions, produces said polypeptide.

5. A recombinant host cell produced by the process of claim 4.

6. A membrane of a recombinant host cell of claim 5 expressing said polypeptide.

7. A process for producing a polypeptide which comprises culturing a host cell of claim 5 under conditions sufficient for the production of said polypeptide and recovering said polypeptide from the culture.