Novel compounds

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, selectins, 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 1 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. In a further aspect, the present invention relates to polynucleotides of the genes set forth in Table I. Such polynucleotides include:

[0021] (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;

[0022] (b) an isolated polynucleotide comprising a polynucleotide set forth in the Sequence Listing;

[0023] (c) an isolated polynucleotide having at least 95%, 96%, 97%, 98%, or 99% identity to a polynucleotide set forth in the Sequence Listing;

[0024] (d) an isolated polynucleotide set forth in the Sequence Listing;

[0025] (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;

[0026] (f) an isolated polynucleotide comprising a polynucleotide sequence encoding a polypeptide set forth in the Sequence Listing;

[0027] (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;

[0028] (h) an isolated polynucleotide encoding a polypeptide set forth in the Sequence Listing;

[0029] (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;

[0030] (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 polynucleotides that are fragments and variants of the above mentioned polynucleotides or that are complementary to above mentioned polynucleotides, over the entire length thereof.

[0031] 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.

[0032] 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).

[0033] 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.

[0034] 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:

[0035] (a) comprises an RNA transcript of the DNA sequence encoding a polypeptide set forth in the Sequence Listing;

[0036] (b) is a RNA transcript of a DNA sequence encoding a polypeptide set forth in the Sequence Listing;

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

[0038] (d) is a RNA transcript of a DNA sequence set forth in the Sequence Listing; and RNA polynucleotides that are complementary thereto.

[0039] 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 Listingis 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.

[0040] 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.

[0041] 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.

[0042] 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.

[0043] 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.

[0044] 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.

[0045] 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.

[0046] 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.

[0047] 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.

[0048] 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.

[0049] 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.

[0050] 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.

[0051] 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.

[0052] 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.

[0053] 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).

[0054] 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.

[0055] 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.

[0056] Thus in another aspect, the present invention relates to a diagnostic kit comprising:

[0057] (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;

[0058] (b) a nucleotide sequence complementary to that of (a);

[0059] (c) a polypeptide of the present invention, preferably the polypeptide set forth in the Sequence Listing or a fragment thereof; or

[0060] (d) an antibody to a polypeptide of the present invention, preferably to the polypeptide set forth in the Sequence Listing.

[0061] 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.

[0062] 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 Mar;5(3):33946 A radiation hybrid map of the human genome. Gyapay G, Schmitt 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/.

[0063] 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.

[0064] 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.

[0065] 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).

[0066] 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.

[0067] 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.

[0068] 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.

[0069] 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.

[0070] 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.

[0071] 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).

[0072] 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)).

[0073] 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.

[0074] 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.

[0075] 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.

[0076] 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

[0077] Screening kits for use in the above described methods form a further aspect of the present invention. Such screening kits comprise:

[0078] (a) a polypeptide of the present invention;

[0079] (b) a recombinant cell expressing a polypeptide of the present invention;

[0080] (c) a cell membrane expressing a polypeptide of the present invention; or

[0081] (d) an antibody to a polypeptide of the present invention;

[0082] which polypeptide is preferably that set forth in the Sequence Listing.

[0083] It will be appreciated that in any such kit, (a), (b), (c) or (d) may comprise a substantial component.

[0084] Glossary

[0085] The following definitions are provided to facilitate understanding of certain terms used frequently hereinbefore.

[0086] “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 Fab or other immunoglobulin expression library.

[0087] “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.

[0088] “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.

[0089] “Secreted protein gene” refers to a polynucleotide comprising any of the attached nucleotide sequences or allelic variants thereof and/or their complements.

[0090] “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.

[0091] “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).

[0092] “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.

[0093] “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.

[0094] “Allele” refers to one of two or more alternative forms of a gene occurring at a given locus in the genome.

[0095] “Polymorphism” refers to a variation in nucleotide sequence (and encoded polypeptide sequence, if relevant) at a given position in the genome within a population.

[0096] “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.

[0097] “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.

[0098] “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.

[0099] “% 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.

[0100] “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.

[0101] 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, 482489, 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.

[0102] 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).

[0103] 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.

[0104] 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.

[0105] “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 mutandis for other values of the Identity Index, for instance 0.96, 0.97, 0.98 and 0.99.

[0106] 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 mutandis for other values of the Identity Index, for instance 0.96, 0.97, 0.98 and 0.99.

[0107] 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)

[0108] in which:

[0109] na is the number of nucleotide or amino acid differences,

[0110] xa is the total number of nucleotides or amino acids in a sequence set forth in the Sequence Listing,

[0111] I is the Identity Index,

[0112] · is the symbol for the multiplication operator, and in which any non-integer product of xa and I is rounded down to the nearest integer prior to subtracting it from xa.

[0113] “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 polynucleotideor polypeptide that within the same species which is functionally similar.

[0114] “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.

[0115] 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.

1TABLE IGSKCorrespondingGeneNucleic AcidProteinGene NameIDSEQ ID NO'sSEQ ID NO'ssbg458463PERLAXINa458463SEQ ID NO: 1SEQ ID NO: 29SEQ ID NO: 2SEQ ID NO: 30sbg507885RDPa507885SEQ ID NO: 3SEQ ID NO: 31SEQ ID NO: 4SEQ ID NO: 32sbg507885RDPb507885SEQ ID NO: 5SEQ ID NO: 33SBh511364.NR-CAMa511364SEQ ID NO: 6SEQ ID NO: 34SEQ ID NO: 7SEQ ID NO: 35SBh511364.NR-CAMb511364SEQ ID NO: 8SEQ ID NO: 36SBh511827.C1q-related511827SEQ ID NO: 9SEQ ID NO: 37factorSEQ ID NO: 10SEQ ID NO: 38sbg533677PALSa533677SEQ ID NO: 11SEQ ID NO: 39SEQ ID NO: 12SEQ ID NO: 40sbg535067MELAa535067SEQ ID NO: 13SEQ ID NO: 41sbg590979THP590979SEQ ID NO: 14SEQ ID NO: 42SEQ ID NO: 15SEQ ID NO: 43sbg658629CRF658629SEQ ID NO: 16SEQ ID NO: 44SEQ ID NO: 17SEQ ID NO: 45sbg507131mannosidase507131SEQ ID NO: 18SEQ ID NO: 46SEQ ID NO: 19SEQ ID NO: 47sbg655871calgizzarin-655871SEQ ID NO: 20SEQ ID NO: 48likeSEQ ID NO: 21SEQ ID NO: 49sbg506454MPG-1506454SEQ ID NO: 22SEQ ID NO: 50SEQ ID NO: 23SEQ ID NO: 51sbg659837OBCAM659837SEQ ID NO: 24SEQ ID NO: 52SEQ ID NO: 25SEQ ID NO: 53sbg467870CBP467870SEQ ID NO: 26SEQ ID NO: 54sbg514112RNase514112SEQ ID NO: 27SEQ ID NO: 55sbg962274FGF-BP962274SEQ ID NO: 28SEQ ID NO: 56

[0116]

2

TABLE II

Cell

localization

Gene
Closest Polynuclotide by
Closest Polypeptide by
(by

Gene Name
Family
homology
homology
homology)

sbg458463PERLAXINa
Periaxin
GB: AC010271
Human periaxin,
Cytosolic

protein
Submitted (15-SEP-1999)
gi: 13649706

by Production Sequencing
Submitted (17-APR-2001) by

Facility, DOE Joint
National Center for

Genome Institute
Biotechnology Information,

NIH, Bethesda, MD 20894,

USA

sbg507885RDPa
Renal
JGI: RPCI-11_331B16
Human putative
Secreted

dipeptidase
Found at Joint Genome
metallopeptidase (family

Institute, Department of
M19), gi: 11641273

Energy, USA
Submitted (02-NOV-2000) by

Chen J. M., MRC Molecular

Enzymology Laboratory, The

Babraham Institute,

Babraham, Cambridge, CB2

4AT, UNITED KINGDOM

sbg507885RDPb
Renal
JGI: RPCI-11_331B16
Human putative
Secreted

dipeptidase
Found at Joint Genome
metallopeptidase (family

Institute, Department of
M19), gi: 11641273

Energy, USA
Submitted (02-NOV-2000) by

Chen J. M., MRC Molecular

Enzymology Laboratory, The

Babraham Institute,

Babraham, Cambridge, CB2

4AT, UNITED KINGDOM

SBh511364.NR-
Immuno
EMBL: AC073550
Human hypothetical protein,
Membrane-

CAMa
globulin
Submitted (22-JUN-2000)
gi: 6807875
bound

superfamily,
Genome Sequencing
Submitted (15-JAN-2000)

neuronglia
Center, Washington
MIPS, Am Klopferspitz 18a,

cell
University School of
D-82152 Martinsried,

adhesion
Medicine, 4444 Forest
GERMANY

molecule-
Park Parkway, St. Louis,

related
MO 63108, USA

protein

(Nr-

CAM)

SBh511364.NR-
Neuronglia
EMBL: AC073550
Human hypothetical protein,
Cytosolic

CAMb
cell
Submitted (22-JUN-2000)
gi: 13632065

adhesion
Genome Sequencing
Submitted (17-APR-2001) by

molecule-
Center, Washington
National Center for

related
University School of
Biotechnology Information,

protein
Medicine, 4444 Forest
NIH, Bethesda, MD 20894,

(Nr-
Park Parkway, St. Louis,
USA

CAM)
MO 63108, USA

SBh511827.C1q-
Complement-
GB: AC026707
Human complement-c1q
Secreted

related
c1q
Submitted (23-MAR-
tumor necrosis factor-related

factor
tumor
2000) by Production
protein, gi: 13569919

necrosis
Sequencing Facility, DOE
Maeda T, Abe M, Kurisu K,

factor-
Joint Genome Institute,
Jikko A and Furukawa S

related
2800 Mitchell Drive,
J Biol Chem 2001 Feb

protein
Walnut Creek, CA 94598,
2; 276(5): 3628-34

USA

sbg533677PALSa
Palmitoylated 3
GB: AL135978
Mouse palmitoylated 3
Membrane-

(MAGUK
Submitted (15-MAY-
(MAGUK p55 subfamily
bound

p55
2001) Genoscope -
member 5), gi: 9625023

subfamily
Centre National de
Kamberov, E., Makarova, O.,

member 5,
Sequencage: BP 191
Roh, M., Liu, A., Karnak, D.,

proteins
91006 EVRY cedex -
Straight, S. and Margolis, B.

associated
FRANCE
J. Biol. Chem. 275 (15),

with Lin-7

11425-11431 (2000).

(PALs)

sbg535067MELAa
Melanoma
SC: AL096827
Unidentified human gene,
Membrane-

associated
Submitted (13-SEP-
gi: 10047249
bound

protein
1999) by Sanger Centre,
Submitted (03-AUG-2000)

Hinxton,
by Osamu Ohara, Kazusa

Cambridgeshire, CB10
DNA Research Institute,

1SA, UK.
Department of Human Gene

Research; 1532-3, Yana,

Kisarazu, Chiba 292-0812,

Japan

sbg590979THP
Tamm-
GB: AC069548
Human pancreatic zymogen
Secreted

Horsfall
Direct submitted (02-
granule membrane protein

protien
JUN-2000) Genome
GP2, gi: 4504075

(THP)
Therapeutics
Wong, S. M. and

Corporation, 100 Beaver
Lowe, A. W.

Street, Waltham, MA
Gene 171 (2), 311-312

02453, USA
(1996)

sbg658629CRF
C1q-related
GB: AC010173
Human C1q-related factor,
Secreted

factor
Direct submitted (15-
gi: 5729785

SEP-1999) Human
Berube N G, Swanson X H,

Genome Sequencing
Bertram M J, Kittle J D,

Center, Department of
Didenko V, Baskin D S,

Molecular and Human
Smith JR and Pereira-Smith

Genetics, Baylor College
OM. Brain Res. Mol. Brain

of Medicine, One Baylor
Res. 63 (2), 233-240 (1999)

Plaza, Houston,

TX77030, USA

sbg507131mannosidase
Alpha-
GB: AC004480
Mouse mannosidase 2,
Secreted

mannosidase
Direct submitted (27-
alpha B2, gi: 6678792

MAR-1998) Department
Hiramoto, S., Tamba, M.,

of Genetics, Stanford
Kiuchi, S., Jin, Y. Z.,

Human Genome Center,
Bannai, S., Sugita, Y.,

855 California Avenue,
Dacheux, F., Dacheux, J. L.,

Palo Alto, CA 94304,
Yoshida, M. and

USA.
Okamura, N.

Biochem. Biophys. Res.

Commun. 241 (2), 439-445

(1997)

sbg655871calgizzarin-like
S100
GB: AC027667
Mouse calgizzarin
Secreted

calcium-
Direct submitted (01-
(endothelial monocyte

binding
APR-2000) Human
activating polypeptide),

protein
Genome Sequencing
gi: 1710819,

Center, Department of
Fan, Y., Leung, D.,

Molecular and Human
Houck, K. A., Yan, S.,

Genetics, Baylor College
Brett, J., Heath, M., Pan, Y.,

of Medicine, One Baylor
Clauss, M., Kisiel, W.,

Plaza, Houston, TX
Chabot, J., Logerfo, P.,

77030, USA
Stern, D. and Kao, J.

submitted (JAN-1996) to

the EMBL/GenBank/DDBJ

databases

sbg506454MPG-1
Macrophage
GB: AP000406
Mouse MPS1 protein
Secreted

Gene-1
Submitted (27-AUG-
gi: 2137564

Product
1999) Masahira Hattori,
Spilsbury, K., O'Mara, M. A.,

(MGP1)
The Institute of Physical
Wu, W. M., Rowe, P. B.,

and Chemical Research
Symonds, G. and

(RIKEN), Genomic
Takayama, Y.

Sciences Center (GSC);
Blood 85 (6), 1620-1629

1-15-1 Kitasato,
(1995)

Sagamihara, Kanagawa

228-8555, Japan

sbg659837OBCAM
Opoid-
GB: AC016769
Bovine opoid-binding cell
Secreted

binding cell
Submitted (25-MAY-
adhesion molecule

adhesion
2001) Genome
Schofield, P. R.,

molecule
Sequencing Center,
McFarland, K. C.,

(OBCAM)
Washington University
Hayflick, J. S., Wilcox, J. N.,

School of Medicine,
Cho, T. M., Roy, S.,

4444 Forest Park
Lee, N. M., Loh, H. H. and

Parkway, St. Louis, MO
Seeburg, P. H. EMBO J. 8

63108, USA
(2), 489-495 (1989)

sbg467870CBP
EF-hand
GB: AC018638
Rat CBP-50 protein,
Endopiasmic

protein
Direct submitted (15-
gi: 2511701
reticulum-

DEC-1999) Human
Submitted (04-OCT-1997)
bound

Genome Center,
by Hseu M. J., Institute of
(secreted if

University of
Biological Chemistry,
C-terminus

Washington, Box
Academia Sinica, Taiwan,
HDEF were

352145, Seattle, WA
R. O. C., P. O. Box 23-106,
deleted)

98195, USA.
Taipei, Taiwan, 10098,

REPUBLIC OF CHINA

sbg514112RNase
RNase
GB: AL355075
Mouse putative protein,
Secreted

Direct submitted (06-
gi: 12853968

JUN-2000) to the
Carninci, P., Shibata, Y.,

EMBL/GenBank/DDBJ
Hayatsu, N., Sugahara, Y.,

databases by Genoscope.
Shibata, K., Itoh, M.,

Konno, H., Okazaki, Y.,

Muramatsu, M. and

Hayashizaki, Y.

Genome Res. 10 (10), 1617-1630

(2000)

sbg962274
Fibroblast
EMBL: AL359198
Mouse putative protein,
Secreted

FGF-BP
growth
Found at Sanger Centre
gi: 12853968

factor
and submitted (08-APR-
Carninci, P., Shibata, Y.,

binding
2001) Sanger Centre,
Hayatsu, N., Sugahara, Y.,

protein
Hinxton,
Shibata, K., Itoh, M.,

Cambridgeshire, CB10
Konno, H., Okazaki, Y.,

1SA, UK.
Muramatsu, M. and

Hayashizaki, Y.

Genome Res. 10 (10), 1617-1630

(2000)

[0117]

3

TABLE III

Associated

Gene Name
Uses
Diseases

sbg458463PERLAXINa
An embodiment of the invention is the use of
Peripheral

sbg458463PERLAXINa in axon-glial interactions. A close
myelinopathies,

homologue of sbg458463PERLAXINa is the rat periaxin (PRX).
infection, cancer,

Rat periaxin (PRX), a protein of myelinating Schwann cells. Periaxin
autoimmune

has a role in axon-glial interactions, possibly by interacting with the
disorders, wound

cytoplasmic domains of integral membrane proteins such as myelin-
healing disorders

associated glycoprotein in the periaxonal regions of the Schwann cell
and

plasma membrane (Gillespie C S, Sherman D L, Blair G E, Brophy P J.
hematopoietic

Periaxin, a protein of myelinating Schwann cells with a possible role
disorders

in axonal ensheathment. Neuron 1994 Mar; 12(3): 497-508). Prx(-/-)

mice develop a severe demyelinating peripheral neuropathy, despite

apparently normal initial formation of myelin sheaths. Three

unrelated Dejerine-Sottas neuropathy patients with recessive PRX

mutations have been identified. It was hypothesized that mutations

in PRX could cause human peripheral myelinopathies

(Boerkoel, C. F., Takashima, H., Stankiewicz, P., Garcia, C. A.,

Leber, S. M., Rhee-Morris, L. and Lupski, J. R. Am. J. Hum. Genet.

68 (2), 325-333 (2001)).

sbg507885RDPa
An embodiment of the invention is the use of sbg507885RDPa in in
Cancer, infection,

the renal metabolism. Close homologues of sbg507885RDPa are
autoimmune

microsomal dipeptidases. The renal dipeptidase (RDP), previously
disorder,

referred to as microsomal dipeptidase, is a kidney membrane
inflammation,

enzyme which hydrolyzes a variety of dipeptides, and is implicated
and acute renal

in the renal metabolism. RDP is responsible for hydrolysis of the
failure

beta-lactam ring of antibiotics (Campbell B J, Forrester L J, Zahler W L,

Burks M; 1984; Biol Chem 259: 14586-90). The renal

dipeptidase has been shown to be a glycosylphosphatidylinositol-

anchored ectoenzyme within the renal proximal tubules, and is

proposed as a diagnostic enzyme of renal disease (Kang B Y, We J S,

Choi K, Lee H B, Han H J, Park H; 1999; Arch Pharm Res

22: 367-71).

sbg507885RDPb
An embodiment of the invention is the use of sbg507885RDPb in in
Cancer, infection,

the renal metabolism. Close homologues of sbg507885RDPb are
autoimmune

microsomal dipeptidases. The renal dipeptidase (RDP), previously
disorder,

referred to as microsomal dipeptidase, is a kidney membrane
inflammation,

enzyme which hydrolyzes a variety of dipeptides, and is implicated
and acute renal

in the renal metabolism. RDP is responsible for hydrolysis of the
failure

beta-lactam ring of antibiotics (Campbell B J, Forrester L J, Zahler

W L, Burks M; 1984; Biol Chem 259: 14586-90). The renal

dipeptidase has been shown to be a glycosylphosphatidylinositol-

anchored ectoenzyme within the renal proximal tubules, and is

proposed as a diagnostic enzyme of renal disease (Kang B Y, We J S,

Choi K, Lee H B, Han H J, Park H; 1999; Arch Pharm Res

22: 367-71).

SBh511364.NR-CAMa
An embodiment of the invention is the use of SBh511364.NR-
Cancer such as

CAMa in the pathogenesis and invasive/metastatic behavior of
pancreatic

pancreatic cancers. A close homologue of SBh511364.NR-CAMa
cancers,

is neural cell adhesion molecule Nr-CAM protein. Nr-CAM protein
infections,

has been detected in the brain and normal human pancreas. Its
autoimmune

expression was markedly up-regulated in intraductal hyperplasia.
diseases,

Expression was well maintained in well or moderately
and neurological

differentiated carcinoma but was reduced or absent from most
disorders

poorly differentiated tumors. In addition, 4 of 4 human pancreatic

adenocarcinoma cell lines tested demonstrated little or no Nr-CAM

expression. This differential regulation of Nr-CAM expression

suggests that it may be involved in the pathogenesis and

invasive/metastatic behavior of pancreatic cancers (Dhodapkar K M,

Friedlander D, Scholes J, Grumet M. Hum Pathol 2001

Apr; 32(4): 396-400).

SBh511364.NR-CAMb
An embodiment of the invention is the use of SBh511364.NR-
Hematopoietic

CAMb as a marker for diagnosing, treating, inhibiting or preventing
disorder, wound

malignancies like brain cancer, leukemia, B celllymphoma,
healing disorders,

premalignant conditions, benign tumors, hyperproliferative
autoimmune

disorders or benign dysproliferative disorders. Similar protein's
diseases, viral

treatment is especially useful for treating glioblastoma,
and bacterial

glioma, meningioma, astrocytoma, medulloblastoma,
infections,

neuroectodermal cancer and neuroblastoma, especially
cancer such as

glioblastoma multiforme (WO9955380-A1, 04-NOV-99; Boynton Al,
meningioma,

Murphy Gp, Sehgal A. Pacific Northwest Cancer Foundation).
astrocytoma,

medulloblastom,

neuroectodermal

and

neuroblastoma,

especially

glioblastoma

SBh511827.C1q-
An embodiment of the invention is the use of SBh511827.C1q-
Hematopoietic

related
related factor in diagnosing and treating lung cancer and
disorder, skeletal

factor
neurological disorders such as Parkinson's disease, Alzheimer's
development

disease and schizophrenia as well as. A close homologue of
disorder, wound

SBh511827.C1q-related factor is collagenous repeat-containing
healing disorders,

sequence of 26-kDa protein (CORS26). Northern blot analysis
autoimmune

revealed that CORS26 mRNA was present at high levels in rib
diseases, viral

growth plate cartilage and at moderate levels in kidney of adult
and bacterial

mice. High levels of CORS26 mRNA were also detected in
infections, lung

condensed prechondrocytic cells of cartilage primordia and
tumor, cancer

developing cartilages in mouse embryos between 13 and 15 days
and growth

postcoitus. Overexpression of CORS26 enhanced the growth of
abnormalities,

C3H10T1/2 cells in vitro. These data suggested that the CORS26
parkinson's

gene might play an important role in skeletal development. Related
disease,

polypeptides have been reported useful for diagnosing and treating
alzheimer's

lung cancer(WO199938973-A2, FRUDAKIS T N, LODES M J,
disease and

MOHAMATH R, REED SG; 05-AUG-99; (CORI-) CORIXA
schizophrenia

CORP), and neurological disorders such as Parkinson's disease,

Alzheimer's disease and schizophrenia(WO199942576-A1,

BARNES M R, 26-AUG-99; (SMIK) SMITHKLINE BEECHAM

PL.

sbg533677PALSa
An embodiment of the invention is the use of sbg533677PALSa in
Cancer, infection,

the proper targeting of growth factor receptors to the basolateral
autoimmune

surface of epithelial cells. A close homologue of sbg533677PALSa
disorders, wound

is the mouse protein, Pals. Pals represents a new subfamily of
healing disorders

membrane-associated guanylate kinases that allow for multiple
and

targeting complexes containing mLin-7 that is necessary for the
hematopoietic

proper targeting of the Let-23 growth factor receptor to the
disorders

basolateral surface of epithelial cells (Kamberov E, Makarova O,

Roh M, Liu A, Karnak D, Straight S, Margolis B Molecular cloning

and characterization of Pals, proteins associated with mLin-7. J

Biol Chem 2000 Apr 14; 275(15): 11425-31).

sbg535067MELAa
An embodiment of the invention is the use of sbg535067MELAa in
Melanoma

detection, treatment and prevention of cancers, e.g. melanoma. A

close homologue of sbg535067MELAa is a human melanoma-

associated antigen. Human melanoma-associated antigen may be

useful in detection, treatment and prevention of cancers. (Pavitt R.

dJ142F18.1 similar to melanoma-associated antigen. Accession no.

CAA19928, Submitted (11-FEB-1999) Sanger Centre, Hinxton,

Cambridge shire, CB10 1SA, UK)

sbg590979THP
An embodiment of the invention is the use of sbg590979THP in
Cancer, infection

regulating cytokine circulation. A close homologue of
autoimmune

sbg590979THP is a Human Tamm-Horsfall Protein. Human
disorder,

Tamm-Horsfall Protein, a major urinary protein, is linked to
hematopoietic

membranes via a glycosylphosphatidylinositol (GPI) anchor, and
disorder, wound

mainly exists at the luminal face of cells of the thick ascending
healing disorders,

limb of Henle's loop (TAL) and early distal convoluted tubules of
inflammation,

nephron. A portion of the Tamm-Horsfall protein is cleaved by the
diabetic

action of proteases, and subsequently is secreted in urine. Since the
nephropathy, and

urinary Tamm-Horsfall protein has a high gel-forming tendency, it
nephrolithiasis

has been postulated that it takes part in the water impermeability of

TAL. It is also proposed that the Tamm-Horsfall protein may

inhibit the colonization of pathogens in the renal mucosa in that the

soluble form competes with that exposed at the plasma membrane

(Pressac M; 2000; Ann Biol Clin (Paris) 58: 167-76)

sbg658629CRF
An embodiment of the invention is the use of sbg658629CRF in
Nervous system

regulating central nervous system functions, e.g. motor functions.
disorder

A close homologue of sbg658629CRF is C1q. C1q is a subunit of

the C1 enzyme complex that activates the serum complement

system. It has been shown that human CRF transcript is expressed

at highest levels in the brain, particularly in the brainstem.

Similarly, in mouse brain CRF transcripts are most abundant in

areas of the nervous system involved in motor function (Berube N G,

Swanson X H, Bertram M J, Kittle JD, Didenko V, Baskin D S,

Smith J R, and Pereira-Smith OM., 1999, Brain Res. Mol. Brain

Res. 63: 233-240).

sbg507131mannosidase
An embodiment of the invention is the use of
Cancer,

sbg507131mannosidase in cell-cell and cell-substratum interactions
infection,

affecting processes such as lymphocyte trafficking, immune cell
autoimmune

stimulation, embryogenesis, and cancer metastasis. A close
disorder,

homologue of sbg507131mannosidase is Alpha-D-mannosidase.
hematopoietic

Alpha-D-mannosidase is involved in the catabolism of
disorder,

glycoproteins through the sequential degradation of mannose and
wound healing

complex oligosaccharides. Specific carbohydrate structures are
disorders,

involved in cell-cell and cell-substratum interactions affecting
inflammation,

processes such as lymphocyte trafficking, immune cell stimulation,
and aplha-

embryogenesis, and cancer metastasis. Therefore, alpha-
mannosidosis

mannosidase inhibitors have been selected as anticancer agents for

clinical tests (Goss P E, Baker M A, Carver J P, Dennis 1W; 1995;

Clin Cancer Res 1: 935-44). Besides, in the human alpha-

mannosidosis is an autosomal recessive lysosomal storage disease

caused by the deficiency of lysosomal alpha-D-mannosidase

activity (Beccari T, Stinchi S, Orlacchio A; 1999; Biosci Rep

19: 157-62).

sbg655871calgizzarin-
An embodiment of the invention is the use of
Cancer, infection,

like
sbg655871calgizzarin-like in the regulation of cell transformation
autoimmune

and/or differentiation. A close homologue of
disorder,

sbg655871calgizzarin-like is human calgizzarin. The expression of
hematopoietic

human calgizzarin was remarkably elevated in colorectal cancers
disorder, wound

(Tanaka M, Adzuma K, Iwami M, Yoshimoto K, Monden Y,
healing disorders,

Itakura. 1995 Cancer. Lett 89: 195-200). In addition, it has been
and inflammation

reported that calgizzarin, or MLN70, is one of several genes

expressed in breast cancer-derived metastatic axillary lymph nodes

but not in normal lymph nodes or breast fibroadenomas (Tomasetto C,

Regnier C, Moog-Lutz C, Mattei M G, Chenard M P, Lidereau R,

Basset P, Rio M C. 1995. Genomics 28: 367-76). It is becoming

clear that calgizzarin-related proteins may be involved in the

regulation of cell transformation and/or differentiation (Moog-Lutz C,

Bouillet P, Regnier C H, Tomasetto C, Mattei M G, Chenard M P,

Anglard P, Rio M C, Basset P. 1995. Int J Cancer 63: 297-303).

sbg506454MPG-1
An embodiment of the invention is the use of sbg506454MPG-1 in
Cancer, infection,

regulating the immune system and familial hemophagocytic
autoimmune

lymphohistiocytosis. Close homologues of sbg506454MPG-1 are
disorder,

human mpg-1 and perforin. It was shown that the mpg-1 gene may
hematopoietic

be specifically expressed in macrophages, and it shares a distant
disorder, wound

ancestry to perform, a lytic protein found in cytotoxic T
healing disorders,

lymphocytes and natural killer cells (Spilsbury K, O'Mara M A, Wu W M,
and inflammation

Rowe P B, Symonds G, Takayama Y. 1995. Blood 85: 1620-9).

Analyses of mice deficient in perforin demonstrate that cytolysis

is critical for immunity against some infections (Harty J T,

Tvinnereim A R, White D W. 2000. Annu Rev Immunol 18: 275-30).

Mutations in the perforin gene were recently identified in familial

hemophagocytic lymphohistiocytosis, a fatal disease of early

childhood (Fadeel B, Henter J I, Orrenius S. 2000. Lakartidningen

97: 1395-400)

sbg659837OBCAM
An embodiment of the invention is the use of sbg659837OBCAM
Cancer, infection,

in cell recognition and adhesion. Close homologues of
autoimmune

sbg659837OBCAM are opoid-binding proteins. The opoid-binding
disorder,

protein binds opoid alkaloids in the presence of acidic lipids. It has
hematopoietic

been shown that the opoid-binding protein shares structural
disorder, wound

homology with members of the immunoglobulin protein
healing disorders,

superfamily, most notably with cell-adhesion molecules, such as
and inflammation

neural cell adhesion molecules (NCAM) and myelin associated

glycoproteins (MAG) (Schofield P R, McFarland K C, Hayflick J S,

Wilcox J N, Cho T M, Roy S, Lee N M, Loh H H, Seeburg P H. 1989.

EMBO J 8: 489-95). It has been shown that opoids can modulate

cell-cell interactions of monocytes, and support for links between

opoids and the immune system (Loh H H, Smith A P. 1990; Annu

Rev Pharmacol Toxicol 30: 123-47).

sbg467870CBP
An embodiment of the invention is the use of sbg467870CBP in
Cancer, infection,

tumor cell invasiveness. A close homologue of sbg467870CBP is
autoimmune

reticulocalbin. Reticulocalbin is a calcium-binding protein located
disorder,

in the lumen of the E R. The protein contains six conserved regions
hematopoietic

with similarity to a high affinity calcium-binding motif, the EF-
disorder, wound

hand (Ozawa M, Muramatsu T. 1993. J Biol Chem 268: 699-705). It
healing disorders,

has been shown that reticulocalbin was overexpressed in highly
and inflammation

invasive breast cancer cell lines, but not in poorly invasive ones

(Liu Z, Brattain M G, Appert H. 1997. Biochem Biophys Res

Commun 231: 283-9).

sbg514112RNase
An embodiment of the invention is the use of sbg514112RNase as a
Cancer, infection,

tool for anticancer therapy and the antagonist of this RNase may be
autoimmune

useful in treating apoptosis-related disorders. A close homologue
disorder,

of sbg514112RNase is human keratinocyte-derived RNase-like
hematopoietic

protein (AAY44192). It has been shown that a genetic-engineered
disorder, wound

pancreatic RNase has cytotoxic action on mouse and human tumor
healing disorders,

cells, but lacks any appreciable toxicity on human and mouse
and inflammation

normal cells. This variant of human pancreatic RNase selectively

sensitized cells derived from a human thyroid tumor to apoptotic

death. Because of its selectivity for tumor cells, and because of its

human origin, this protein was thought to represent a promising tool

for anticancer therapy (Piccoli R, Di Gaetano S, De Lorenzo C,

Grauso M, Monaco C, Spalletti-Cernia D, Laccetti P, Cinatl J,

Matousek J, D'Alessio G. 1999. Proc Natl Acad Sci USA 96: 7768-73).

sbg962274FGF-BP
An embodiment of the invention is the use of sbg962274FGF-BP as
Cancer, infection,

a modulator of FGF in FGF-responsive cells and/or detection,
autoimmune

treatment and prevention of cancers. A close homologue of
disorder,

sbg962274FGF-BP is mouse fibroblast growth factor binding
hematopoietic

protein 1 (gi: 7106317). Murine FGF-BP binds to FGF-2 and can
disorder, wound

function as a modulator of FGF in FGF-responsive cells. FGF-BP
healing disorders,

mRNA expression in the adult skin was dramatically increased
inflammation,

during early stages of carcinogen-induced transformation in vivo
osteoporosis,

and by ras-activation (Kurtz A, Wang H L, Darwiche N, Harris V,
Alzheimer's

Wellstein A. 1997. Oncogene Jun 5; 14(22): 2671-81). The
disease,

induction of the angiogenic modulator FGF-BP by epidermal
Parkinson's

growth factor was mediated through both MEK/ERK and p38
disease, asthma,

signal transduction pathways (Harris V K, Coticchia C M, Kagan
multiple

B L, Ahmad S, Wellstein A, Riegel A T. 2000. J Biol Chem Apr
sclerosis and

14; 275(15): 10802-11). Further more, the FGF-BP was upregulated
rheumatoid

in carcinogen-induced skin tumors, in squamous cell carcinoma

(SCC) and in some colon cancer cell lines and tumor samples

(Harris V K, Coticchia C M, List H J, Wellstein A, Riegel A T. 2000.

J Biol Chem Jun 27). Finally, human tumors can utilize FGF-BP

as an angiogenic switch molecule, the growth and angiogenesis of

xenograft tumors in mice was decreased in parallel with the

reduction of FGF-BP. These results indicate the role of FGF-BP in

tumor metastases (Czubayko F, Liaudet-Coopman E D, Aigner A,

Tuveson A T, Berchem G J, Wellstein A. 1997. Med.

Oct; 3(10): 1137-40,. Jayne D G, Perry S L, Morrison E, Farmery S M,

Guillou P J. 2000. Br J Cancer Mar; 82(6): 1233-8).

[0118]

4

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.

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

[0119] Gene Name sbg458463PERLAXINa

[0120] Strongly expressed in brain and lung. Overexpressed in lung tumor (¼).Downregulated in COPD lung. Overexpressed in Alzheimer's disease.

5Meancopies ofGOImRNAcopiesMean GOIAverage50 ng/18Sdetected/50 ngSample(samplecopiesGOIrRNAtotalsbg458463PERLAXINa1)(sample 2)Copies18S rRNA (ng)(ng)RNASubcutaneous41.2319.9341.233.0616.34673.69Adipocytes ZenbioSubcutaneous Adipose0.003.770.000.9652.360.00ZenbioAdrenal Gland Clontech8.113.368.110.6181.97664.75Whole Brain Clontech1249.191199.081249.197.246.918627.00Fetal Brain Clontech4.033.174.030.48103.95418.92Cerebellum Clontech29.602.2629.602.1723.04682.03Cervix0.003.520.002.4220.660.00Colon10.9411.4310.942.7118.45201.85Endometrium19.7510.3919.750.7368.211347.20Esophagus3.420.003.421.3736.50124.82Heart Clontech5.638.285.631.3237.88213.26Hypothalamus9.613.169.610.32155.281492.24Ileum19.500.0019.502.5819.38377.91Jejunum35.7232.2235.726.607.58270.61Kidney6.4213.666.422.1223.58151.42Liver13.553.2813.551.5033.33451.67Fetal Liver Clontech57.5794.1057.5710.404.81276.78Lung124.57127.73124.572.5719.462423.54Mammary Gland60.5830.8460.5813.003.85233.00ClontechMyometrium6.300.006.302.3421.37134.62Omentum3.517.213.513.9412.6944.54Ovary19.1433.0119.144.3411.52220.51Pancreas3.280.003.280.8161.80202.72Head of Pancreas0.005.330.001.5731.850.00Parotid Gland17.050.0017.055.489.12155.57Placenta Clontech36.7712.6336.775.269.51349.52Prostate4.3018.254.303.0016.6771.67Rectum2.6822.552.681.2340.65108.94Salivary Gland Clontech21.5410.8921.547.316.84147.33Skeletal Muscle0.000.000.001.2639.680.00ClontechSkin3.350.003.351.2141.32138.43Small Intestine Clontech0.000.000.000.9851.070.00Spleen4.870.004.874.9210.1649.49Stomach12.6321.3512.632.7318.32231.32Testis Clontech0.000.000.000.5787.870.00Thymus Clontech45.0258.5045.029.895.06227.60Thyroid19.3758.1119.372.7718.05349.64Trachea Clontech24.5232.5224.529.715.15126.26Urinary Bladder17.4818.4317.485.479.14159.78Uterus27.0214.4327.025.349.36253.00copies ofRegmRNAnumberMeandetected/50 ngFold Change inSample(GSKGOItotalDiseasesbg458463PERLAXINaidentifier)copiesRNASamplePopulationcolon normal GW98-16721941253.9507.80colon normalcolon tumor GW98-16621940228.99457.98colon tumor−1.108782043colon normal GW98-17822080149.04298.08colon normalcolon tumor GW98-1772206068.84137.68colon tumor−2.165020337colon normal GW98-5612351461.93123.86colon normalcolon tumor GW98-56023513167.95335.90colon tumor2.711932827colon normal GW98-89424691160.94321.88colon normalcolon tumor GW98-89324690157.68315.36colon tumor−1.020674784lung normal GW98-3207424197.388394.76lung normallung tumor GW98-220741176.65353.30lung tumor−23.76099632lung normal GW97-17920677385.26770.52lung normallung tumor GW97-17820676480.07960.14lung tumor1.246093547lung normal GW98-165219225999.511999.00lung normallung tumor GW98-16421921856.891713.78lung tumor−7.001482104lung normal GW98-28222584377.61755.22lung normallung tumor GW98-281225832559.295118.58lung tumor6.777601229breast normal GW00-39228750408.18408.18breast normalbreast tumor GW00-39128746394.46788.92breast tumor1.932774756breast normal GW00-4132879874.374.30breast normalbreast tumor GW00-41228797258.3516.60breast tumor6.952893674breast normal GW00-27592-9551.7551.75breast normal235: 238breast tumor GW00-27588-91238.94238.94breast tumor4.617198068231: 234breast normal GW98-62123656556.611113.22breast normalbreast tumor GW98-62023655375.74751.48breast tumor−1.481370096brain normal BB99-5422550794588.67189177.34brain normalbrain normal BB99-40625509639.741279.48brain normalbrain normal BB99-90425546230.79461.58brain normalbrain stage 5 ALZ BB99-255021238.352476.70brain stage 5−25.69526655874ALZbrain stage 5 ALZ BB99-255031317.432634.86brain stage 5−24.15288352887ALZbrain stage 5 ALZ BB99-255041028.92057.80brain stage 5−30.92597272862ALZbrain stage 5 ALZ BB99-25542863.061726.12brain stage 5−36.86850663927ALZCT lung KCnormal3367.926735.84CT lunglung 26 KCnormal95.0495.04lung 26lung 27 KCnormal116.4116.40lung 27lung 24 KCCOPD44.244.20lung 24−39.76391403lung 28 KCCOPD15.3815.38lung 28−114.2760078lung 23 KCCOPD23.0623.06lung 23−76.2170425lung 25 KCCOPD82.9882.98lung 25asthmatic lung293212034.332034.33asthmatic lung1.157470705ODO3112asthmatic lung293233155.216310.42asthmatic lung3.590433355ODO3433asthmatic lung293226352.7612705.52asthmatic lung7.229047005ODO3397asthmatic lung293252424.254848.50asthmatic lung2.758646195ODO4928endo cells KCcontrol41.6641.66endo cellsendo VEGF KC51.251.20endo VEGF1.228996639endo bFGF KC45.745.70endo bFGF1.096975516heart Clontechnormal63.06126.12heartheart (T-1) ischemic29417479.42958.84heart T-17.602600698heart (T-14) non-29422410.97821.94heart T-146.517126546obstructive DCMheart (T-3399) DCM29426486.59973.18heart T-33997.716301935adenoid GW99-26926162100.09200.18adenoidtonsil GW98-28022582260.2520.40tonsilT cells PC0031428453257.22514.44T cellsPBMNC KC26.2726.27PBMNCmonocyte KC33.0966.18monocyteB cells PC0066528455144.41288.82B cellsdendritic cells 28441159.67319.34dendritic cellsneutrophils28440444.77444.77neutrophilseosinophils2844623.2946.58eosinophilsBM unstim KC9.269.26BM unstimBM stim KC67.5267.52BM stim7.291576674osteo dif KC50.2750.27osteo difosteo undif KC9.89.80osteo undif−5.129591837chondrocytes275.5688.75chondrocytesOA Synovium IP12/0129462432.44432.44OA SynoviumOA Synovium NP10/0129461315.85631.70OA SynoviumOA Synovium NP57/0028464397.41794.82OA SynoviumRA Synovium NP03/0128466342.52685.04RA SynoviumRA Synovium NP71/0028467439.34878.68RA SynoviumRA Synovium NP45/0028475222.07444.14RA SynoviumOA bone (biobank)29217152.61152.61OA bone(biobank)OA bone Sample 1J. Emory623.731247.46OA boneOA bone Sample 2J. Emory330.6661.20OA boneCartilage (pool)Normal592.051184.10Cartilage(pool)Cartilage (pool)OA204.82409.64Cartilage−2.890586857(pool)PBL unifected28441488.95977.90PBL unifectedPBL HIV IIIB28442261.88523.76PBL HIV IIIB−1.867076524MRC5 uninfected29158476.47952.94MRC5(100%)uninfected(100%)MRC5 HSV strain F29178216.34432.68MRC5 HSV−2.202412869strain FW12 cells29179182.76365.52W12 cellsKeratinocytes29180124.58249.16Keratinocytes

[0121] Gene Name sbg458463PERLAXINa

6Fold Change in DiseasePopulation Relative toDisease tissuesNormalcolon tumor−1.11colon tumor−2.17colon tumor2.71colon tumor−1.02lung tumor−23.76lung tumor1.25lung tumor−7.00lung tumor6.78breast tumor1.93breast tumor6.95breast tumor4.62breast tumor−1.48brain stage 5 ALZ−25.70brain stage 5 ALZ−24.15brain stage 5 ALZ−30.93brain stage 5 ALZ−36.87lung 24−39.76lung 28−114.28lung 23−76.22asthmatic lung1.16asthmatic lung3.59asthmatic lung7.23asthmatic lung2.76endo VEGF1.23endo bFGF1.10heart T-17.60heart T-146.52heart T-33997.72BM stim7.29osteo undif−5.13Cartilage (pool)−2.89PBL HIV IIIB−1.87MRC5 HSV strain F−2.20

[0122] Gene Name sbg507885RDPa and sbg507885RDPb

[0123] Strongly expressed in immune cells. Corroborating expression in OA and RA samples suggesting a role in this disease. Expression in brain outside of cortex, cerebellum, and hypothalamus indicating localized expression in brain.

7copies ofmRNA50 ng/detected/SampleMean GOIMean GOIAverage18S50 ngsbg507885RDPa andcopiescopiesGOIrRNAtotalsbg507885RDPb(sample 1)(sample 2)Copies18S rRNA (ng)(ng)RNASubcutaneous0.440.000.223.0616.343.59Adipocytes ZenbioSubcutaneous Adipose0.001.460.730.9652.3638.22ZenbioAdrenal Gland Clontech2.561.632.100.6181.97171.72Whole Brain Clontech354.41170.16262.297.246.911811.36Fetal Brain Clontech1.811.981.900.48103.95196.99Cerebellum Clontech1.424.833.132.1723.0472.00Cervix1.000.940.972.4220.6620.04Colon7.323.785.552.7118.45102.40Endometrium6.520.993.760.7368.21256.14Esophagus1.300.650.981.3736.5035.58Heart Clontech0.451.811.131.3237.8842.80Hypothalamus0.000.000.000.32155.280.00Ileum14.772.058.412.5819.38162.98Jejunum12.8518.3815.626.607.58118.30Kidney0.710.700.712.1223.5816.63Liver0.8414.927.881.5033.33262.67Fetal Liver Clontech34.5248.2341.3810.404.81198.92Lung0.006.123.062.5719.4659.53Mammary Gland6.691.133.9113.003.8515.04ClontechMyometrium0.000.000.002.3421.370.00Omentum19.3922.1820.793.9412.69263.77Ovary10.108.289.194.3411.52105.88Pancreas0.620.750.690.8161.8042.34Head of Pancreas0.510.800.661.5731.8520.86Parotid Gland0.7912.986.895.489.1262.82Placenta Clontech5.826.216.025.269.5157.18Prostate0.940.000.473.0016.677.83Rectum9.470.595.031.2340.65204.47Salivary Gland1.064.832.957.316.8420.14ClontechSkeletal Muscle0.890.000.451.2639.6817.66ClontechSkin0.700.920.811.2141.3233.47Small Intestine2.380.001.190.9851.0760.78ClontechSpleen5.420.633.034.9210.1630.74Stomach0.0014.377.192.7318.32131.59Testis Clontech29.6916.0022.850.5787.872007.47Thymus Clontech27.9442.8035.379.895.06178.82Thyroid0.005.972.992.7718.0553.88Trachea Clontech35.39143.0289.219.715.15459.35Urinary Bladder0.560.000.285.479.142.56Uterus6.5732.5819.585.349.36183.29copies ofRegmRNASamplenumberMeandetected/50 ngFold Changesbg507885RDPa and(GSKGOItotalin Diseasesbg507885RDPbidentifier)copiesRNASamplePopulationcolon normal GW98-1672194145.6691.32colon normalcolon tumor GW98-1662194043.1886.36colon tumor−1.057433997colon normal GW98-1782208020.1140.22colon normalcolon tumor GW98-1772206010.9621.92colon tumor−1.834854015colon normal GW98-5612351431.6563.30colon normalcolon tumor GW98-5602351317.3234.64colon tumor−1.827367206colon normal GW98-8942469147.8795.74colon normalcolon tumor GW98-8932469019.4938.98colon tumor−2.456131349lung normal GW98-32074292.38184.76lung normallung tumor GW98-22074100.00lung tumor−184.76lung normal GW97-17920677118.63237.26lung normallung tumor GW97-17820676179.06358.12lung tumor1.509398972lung normal GW98-16521922282.77565.54lung normallung tumor GW98-16421921127.86255.72lung tumor−2.211559518lung normal GW98-2822258434.8169.62lung normallung tumor GW98-2812258314.929.80lung tumor−2.336241611breast normal GW00-3922875019.4719.47breast normalbreast tumor GW00-3912874621.6143.22breast tumor2.219825372breast normal GW00-4132879819.7719.77breast normalbreast tumor GW00-4122879728.4756.94breast tumor2.880121396breast normal GW00-27592-958.878.87breast normal235: 238breast tumor GW00-27588-9119.3719.37breast tumor2.183765502231: 234breast normal GW98-6212365640.1480.28breast normalbreast tumor GW98-620236558.9217.84breast tumor−4.5brain normal BB99-54225507136.73273.46brain normalbrain normal BB99-4062550974.17148.34brain normalbrain normal BB99-90425546103.79207.58brain normalbrain stage 5 ALZ BB99-2550215.3130.62brain stage 5−6.851513172874ALZbrain stage 5 ALZ BB99-25503256.01512.02brain stage 52.440592329887ALZbrain stage 5 ALZ BB99-2550475.06150.12brain stage 5−1.397504219862ALZbrain stage 5 ALZ BB99-25542142.17284.34brain stage 51.355333821927ALZCT lung KCnormal51.66103.32CT lunglung 26 KCnormal25.2625.26lung 26lung 27 KCnormal00.00lung 27lung 24 KCCOPD8.848.84lung 24−4.022624434lung 28 KCCOPD2.62.60lung 28−13.67692308lung 23 KCCOPD5.925.92lung 23−6.006756757lung 25 KCCOPD13.6613.66lung 25asthmatic lung ODO31122932122.4722.47asthmatic lung−1.582554517asthmatic lung ODO34332932372.48144.96asthmatic lung4.076490439asthmatic lung ODO33972932289.06178.12asthmatic lung5.008998875asthmatic lung ODO492829325165.77331.54asthmatic lung9.323397075endo cells KCcontrol3.743.74endo cellsendo VEGF KC00.00endo VEGF−3.74endo bFGF KC00.00endo bFGF−3.74heart Clontechnormal44.0588.10heartheart (T-1) ischemic2941734.7169.42heart T-1−1.269086719heart (T-14) non-294226.7813.56heart T-14−6.497050147obstructive DCMheart (T-3399) DCM2942613.4226.84heart T-3399−3.282414307adenoid GW99-2692616279.2158.40adenoidtonsil GW98-2802258292.31184.62tonsilT cells PC0031428453499.1998.20T cellsPBMNC KC16.1716.17PBMNCmonocyte KC8.3316.66monocyteB cells PC00665284551260.772521.54B cellsdendritic cells 28441153.63307.26dendritic cellsneutrophils284405938.245938.24neutrophilseosinophils284461471.532943.06eosinophilsBM unstim KC9.629.62BM unstimBM stim KC31.2331.23BM stim3.246361746osteo dif KC00.00osteo difosteo undif KC00.00osteo undif0chondrocytes0.681.70chondrocytesOA Synovium IP12/012946280.6480.64OA SynoviumOA Synovium NP10/0129461121242.00OA SynoviumOA Synovium NP57/0028464117.75235.50OA SynoviumRA Synovium NP03/0128466189.18378.36RA SynoviumRA Synovium NP71/0028467313.76627.52RA SynoviumRA Synovium NP45/0028475146.34292.68RA SynoviumOA bone (biobank)29217171.21171.21OA bone(biobank)OA bone Sample 1J. Emory71.91143.82OA boneOA bone Sample 2J. Emory132.79265.58OA boneCartilage (pool)Normal19.0638.12Cartilage(pool)Cartilage (pool)OA31.6563.30Cartilage1.660545645(pool)PBL unifected2844199.28198.56PBL unifectedPBL HIV IIIB2844257.94115.88PBL HIV IIIB−1.713496721MRC5 uninfected (100%)2915800.00MRC5uninfected(100%)MRC5 HSV strain F29178206.39412.78MRC5 HSV412.78strain FW12 cells2917900.00W12 cellsKeratinocytes291804.358.70Keratinocytes

[0124] Gene Name sbg507885RDPa and sbg507885RDPb

8Fold Change in DiseasePopulation Relative toDisease tissuesNormalcolon tumor−1.06colon tumor−1.83colon tumor−1.83colon tumor−2.46lung tumor−184.76lung tumor1.51lung tumor−2.21lung tumor−2.34breast tumor2.22breast tumor2.88breast tumor2.18breast tumor−4.50brain stage 5 ALZ−6.85brain stage 5 ALZ2.44brain stage 5 ALZ−1.40brain stage 5 ALZ1.36lung 24−4.02lung 28−13.68lung 23−6.01asthmatic lung−1.58asthmatic lung4.08asthmatic lung5.01asthmatic lung9.32endo VEGF−3.74endo bFGF−3.74heart T-1−1.27heart T-14−6.50heart T-3399−3.28BM stim3.25osteo undif0.00Cartilage (pool)1.66PBL HIV IIIB−1.71MRC5 HSV strain F412.78

[0125] Gene Name SBh511364.NR-CAMa and SBh511364.NR-CAMb

[0126] Strongly expressed in synovium. Specific expression profile and lack of corroborating expression in immune cells indicates that this expression may be derived from synoviocytes. Strongly expressed in brain and to a lesser degree, hypothalamus. Low expression in cortex.

9copiesofSamplemRNASBh511364.NR-detected/CAMa andMean GOIMean GOI50 ng/18S50 ngSBh511364.NR-copiescopiesAverage18S rRNArRNAtotalCAMb(sample 1)(sample 2)GOI Copies(ng)(ng)RNASubcutaneous8.8115.2112.013.0616.34196.24Adipocytes ZenbioSubcutaneous Adipose0.650.600.630.9652.3632.72ZenbioAdrenal Gland5.822.884.350.6181.97356.56ClontechWhole Brain Clontech745.46885.20815.337.246.915630.73Fetal Brain Clontech2.547.104.820.48103.95501.04Cerebellum Clontech2.001.601.802.1723.0441.47Cervix5.245.575.412.4220.66111.67Colon19.129.9114.522.7118.45267.80Endometrium5.893.094.490.7368.21306.28Esophagus3.365.734.551.3736.50165.88Heart Clontech11.194.507.851.3237.88297.16Hypothalamus6.239.337.780.32155.281208.07Ileum22.1314.5418.342.5819.38355.33Jejunum43.0828.6735.886.607.58271.78Kidney6.612.384.502.1223.58106.01Liver5.717.806.761.5033.33225.17Fetal Liver Clontech58.5839.2248.9010.404.81235.10Lung21.5414.2717.912.5719.46348.35Mammary Gland74.1070.1372.1213.003.85277.37ClontechMyometrium14.2014.0014.102.3421.37301.28Omentum10.028.879.453.9412.69119.86Ovary18.1321.7819.964.3411.52229.90Pancreas5.355.015.180.8161.80320.15Head of Pancreas15.4817.7116.601.5731.85528.50Parotid Gland15.6518.0916.875.489.12153.92Placenta Clontech39.7332.5836.165.269.51343.68Prostate11.1810.7010.943.0016.67182.33Rectum13.0318.2515.641.2340.65635.77Salivary Gland45.2337.4041.327.316.84282.59ClontechSkin13.3618.7116.041.2141.32662.60Small Intestine9.3514.9012.130.9851.07619.25ClontechSpleen20.5316.7518.644.9210.16189.43Stomach10.1511.2110.682.7318.32195.60Testis Clontech4.219.046.630.5787.87582.16Thymus Clontech107.5469.6788.619.895.06447.95Thyroid16.4220.7718.602.7718.05335.65Trachea Clontech45.9241.9643.949.715.15226.26Urinary Bladder32.6727.4230.055.479.14274.63Uterus16.5613.1314.855.349.36139.00copies ofSampleRegmRNASBh511364.NR-CAManumberMeandetected/50 ngFold Changeand SBh511364.NR-(GSKGOItotalin DiseaseCAMbidentifier)copiesRNASamplePopulationcolon normal GW98-16721941341.84683.68colon normalcolon tumor GW98-16621940698.491396.98colon tumor2.043324362colon normal GW98-17822080173.88347.76colon normalcolon tumor GW98-1772206069.79139.58colon tumor−2.491474423colon normal GW98-56123514131.42262.84colon normalcolon tumor GW98-5602351389.43178.86colon tumor−1.469529241colon normal GW98-89424691182.2364.40colon normalcolon tumor GW98-89324690119.24238.48colon tumor−1.528010735lung normal GW98-320742366.92733.84lung normallung tumor GW98-220741171.96343.92lung tumor−2.133752035lung normal GW97-17920677779.871559.74lung normallung tumor GW97-17820676276.89553.78lung tumor−2.816533642lung normal GW98-16521922325.67651.34lung normallung tumor GW98-164219211297.392594.78lung tumor3.983756563lung normal GW98-28222584608.411216.82lung normallung tumor GW98-28122583164.45328.90lung tumor−3.699665552breast normal GW00-39228750138.27138.27breast normalbreast tumor GW00-39128746181.83363.66breast tumor2.630071599breast normal GW00-4132879838.9938.99breast normalbreast tumor GW00-4122879790.26180.52breast tumor4.629905104breast normal GW00-27592-9534.6934.69breast normal235: 238breast tumor GW00-27588-91189.47189.47breast tumor5.461804555231: 234breast normal GW98-62123656375.65751.30breast normalbreast tumor GW98-62023655165.82331.64breast tumor−2.265408274brain normal BB99-54225507193.78387.56brain normalbrain normal BB99-4062550990.91181.82brain normalbrain normal BB99-90425546106.82213.64brain normalbrain stage 5 ALZ BB99-25502107.53215.06brain stage 5−1.213645804874ALZbrain stage 5 ALZ BB99-25503178.51357.02brain stage 51.367857781887ALZbrain stage 5 ALZ BB99-25504134.36268.72brain stage 51.029552246862ALZbrain stage 5 ALZ BB99-2554299.03198.06brain stage 5−1.31781615927ALZCT lung KCnormal260.82521.64CT lunglung 26 KCnormal5.725.72lung 26lung 27 KCnormal1.051.05lung 27lung 24 KCCOPD2.042.04lung 24−64.84803922lung 28 KCCOPD2.132.13lung 28−62.10798122lung 23 KCCOPD5.325.32lung 23−24.86654135lung 25 KCCOPD0.750.75lung 25asthmatic lung ODO311229321153.45153.45asthmatic lung1.159951621asthmatic lung ODO343329323324.42648.84asthmatic lung4.904679114asthmatic lung ODO339729322940.061880.12asthmatic lung14.21210976asthmatic lung ODO492829325336.17672.34asthmatic lung5.082319147endo cells KCcontrol17.8717.87endo cellsendo VEGF KC3.693.69endo VEGF−4.842818428endo bFGF KC1.991.99endo bFGF−8.979899497heart Clontechnormal103.46206.92heartheart (T-1) ischemic2941782.96165.92heart T-1−1.24710704heart (T-14) non-2942295.28190.56heart T-14−1.085852225obstructive DCMheart (T-3399) DCM2942682.5165.00heart T-3399−1.254060606adenoid GW99-26926162194.24388.48adenoidtonsil GW98-28022582229.68459.36tonsilT cells PC003142845396.61193.22T cellsPBMNC KC4.334.33PBMNCmonocyte KC19.3438.68monocyteB cells PC006652845587.76175.52B cellsdendritic cells 2844138.0976.18dendritic cellsneutrophils2844037.837.80neutrophilseosinophils2844655.24110.48eosinophilsBM unstim KC9.029.02BM unstimBM stim KC5.155.15BM stim−1.751456311osteo dif KC1.361.36osteo difosteo undif KC1.621.62osteo undif1.191176471chondrocytes15.3338.33chondrocytesOA Synovium IP12/0129462761.5761.50OA SynoviumOA Synovium NP10/0129461331.41662.82OA SynoviumOA Synovium NP57/00284641027.352054.70OA SynoviumRA Synovium NP03/01284661550.083100.16RA SynoviumRA Synovium NP71/00284671537.933075.86RA SynoviumRA Synovium NP45/00284752117.454234.90RA SynoviumOA bone (biobank)2921715.1415.14OA bone(biobank)OA bone Sample 1J. Emory147.58295.16OA boneOA bone Sample 2J. Emory78.86157.72OA boneCartilage (pool)Normal170.3340.60Cartilage(pool)Cartilage (pool)OA107.65215.30Cartilage−1.581978634(pool)PBL unifected284412346.00PBL unifectedPBL HIV IIIB2844229.1158.22PBL HIV IIIB1.265652174MRC5 uninfected (100%)29158181.22362.44MRC5uninfected(100%)MRC5 HSV strain F2917837.2674.52MRC5 HSV−4.863660762strain FW12 cells2917992.73185.46W12 cellsKeratinocytes2918055.64111.28Keratinocytes

[0127] Gene Name SBhS11364.NR-CAMa and SBh511364.NR-CAMb

10Fold Change in DiseasePopulation Relative toDisease tissuesNormalcolon tumor2.04colon tumor−2.49colon tumor−1.47colon tumor−1.53lung tumor−2.13lung tumor−2.82lung tumor3.98lung tumor−3.70breast tumor2.63breast tumor4.63breast tumor5.46breast tumor−2.27brain stage 5 ALZ−1.21brain stage 5 ALZ1.37brain stage 5 ALZ1.03brain stage 5 ALZ−1.32lung 24−64.85lung 28−62.11lung 23−24.87asthmatic lung1.16asthmatic lung4.90asthmatic lung14.21asthmatic lung5.08endo VEGF−4.84endo bFGF−8.98heart T-1−1.25heart T-14−1.09heart T-3399−1.25BM stim−1.75osteo undif1.19Cartilage (pool)−1.58PBL HIV IIIB1.27MRC5 HSV strain F−4.86

[0128] Gene Name SBhs 11827.C1q-related factor

[0129] Expression in T and B cells. Corroborating expression in OA and RA samples suggesting role in this disease. Expression in tumors may be due to infiltration of immune cells. High brain expression in whole brain and cortex but does not correlate with Alzheimer's disease.

11copies ofmRNAdetected/SampleMean GOIAverage50 ng/50 ngSBh511827.C1q-copiesMean GOI copiesGOI18S rRNA18S rRNAtotalrelated factor(sample 1)(sample 2)Copies(ng)(ng)RNASubcutaneous10.015.607.813.0616.34127.53Adipocytes ZenbioSubcutaneous Adipose0.002.571.290.9652.3667.28ZenbioAdrenal Gland Clontech0.000.000.000.6181.970.00Whole Brain Clontech5567.938662.877115.407.246.9149139.50Fetal Brain Clontech0.002.901.450.48103.95150.73Cerebellum Clontech16.4220.3618.392.1723.04423.73Cervix7.425.996.712.4220.66138.53Colon48.7228.0438.382.7118.45708.12Endometrium2.790.001.400.7368.2195.16Esophagus0.000.000.001.3736.500.00Heart Clontech6.470.003.241.3237.88122.54Hypothalamus0.660.000.330.32155.2851.24Ileum93.2338.6765.952.5819.381278.10Jejunum139.5866.22102.906.607.58779.55Kidney3.441.902.672.1223.5862.97Liver5.922.254.091.5033.33136.17Fetal Liver Clontech660.71619.22639.9710.404.813076.75Lung8.3230.5019.412.5719.46377.63Mammary Gland83.57132.39107.9813.003.85415.31ClontechMyometrium3.807.925.862.3421.37125.21Omentum38.71144.1591.433.9412.691160.28Ovary20.3530.4925.424.3411.52292.86Pancreas3.056.194.620.8161.80285.54Head of Pancreas0.000.000.001.5731.850.00Parotid Gland508.91732.28620.605.489.125662.36Placenta Clontech41.4320.4130.925.269.51293.92Prostate3.110.001.563.0016.6725.92Rectum32.5924.2028.401.2340.651154.27Salivary Gland333.69307.24320.477.316.842191.96ClontechSkeletal Muscle0.003.231.621.2639.6864.09ClontechSkin0.000.000.001.2141.320.00Small Intestine0.000.000.000.9851.070.00ClontechSpleen6.2329.0917.664.9210.16179.47Stomach14.4028.9221.662.7318.32396.70Testis Clontech0.002.811.410.5787.87123.46Thymus Clontech1882.591917.191899.899.895.069605.11Thyroid8.335.076.702.7718.05120.94Trachea Clontech114.59259.72187.169.715.15963.72Urinary Bladder71.4789.0780.275.479.14733.73Uterus30.6637.3534.015.349.36318.40copies ofRegmRNASamplenumberMeandetected/50 ngFold ChangeSBh511827.C1q-related(GSKGOItotalin Diseasefactoridentifier)copiesRNASamplePopulationcolon normal GW98-167219415744.0211488.04colon normalcolon tumor GW98-166219406292.5212585.04colon tumor1.095490615colon normal GW98-17822080320.97641.94colon normalcolon tumor GW98-177220601579.813159.62colon tumor4.921986478colon normal GW98-561235141441.032882.06colon normalcolon tumor GW98-56023513593.171186.34colon tumor−2.429371007colon normal GW98-894246913163.536327.06colon normalcolon tumor GW98-893246901149.982299.96colon tumor−2.750943495lung normal GW98-3207423695.927391.84lung normallung tumor GW98-220741731.091462.18lung tumor−5.055355702lung normal GW97-179206771378.742757.48lung normallung tumor GW97-178206761448.642897.28lung tumor1.050698464lung normal GW98-165219223139.746279.48lung normallung tumor GW98-164219218081.5116163.02lung tumor2.573942428lung normal GW98-282225841632.833265.66lung normallung tumor GW98-28122583764.621529.24lung tumor−2.135479061breast normal GW00-392287502333.362333.36breast normalbreast tumor GW00-391287462670.095340.18breast tumor2.288622416breast normal GW00-413287981982.151982.15breast normalbreast tumor GW00-412287971739.483478.96breast tumor1.755144666breast normal GW00-27592-951835.311835.31breast normal235: 238breast tumor GW00-27588-919829.729829.72breast tumor5.35589083231: 234breast normal GW98-621236562824.185648.36breast normalbreast tumor GW98-620236555401.7710803.54breast tumor1.91268616brain normal BB99-542255074282.268564.52brain normalbrain normal BB99-406255095101.6910203.38brain normalbrain normal BB99-904255463412.266824.52brain normalbrain stage 5 ALZ BB99-255021341.142682.28brain stage 5−3.180431076874ALZbrain stage 5 ALZ BB99-255037475.2814950.56brain stage 51.752537665887ALZbrain stage 5 ALZ BB99-255044871.169742.32brain stage 51.142016269862ALZbrain stage 5 ALZ BB99-255424972.659945.30brain stage 51.165810033927ALZCT lung KCnormal622.181244.36CT lunglung 26 KCnormal1547.51547.50lung 26lung 27 KCnormal8.758.75lung 27lung 24 KCCOPD4545.00lung 24−15.69138889lung 28 KCCOPD107.35107.35lung 28−6.577666511lung 23 KCCOPD245.33245.33lung 23−2.878215057lung 25 KCCOPD23.8423.84lung 25asthmatic lung ODO311229321518.92518.92asthmatic lung−1.360734795asthmatic lung ODO343329323893.671787.34asthmatic lung2.53123971asthmatic lung ODO3397293222195.274390.54asthmatic lung6.217904371asthmatic lung ODO492829325695.541391.08asthmatic lung1.970054347endo cells KCcontrol16.4916.49endo cellsendo VEGF KC119.58119.58endo VEGF7.251667677endo bFGF KC17.0517.05endo bFGF1.033959976heart Clontechnormal166.69333.38heartheart (T-1) ischemic294171046.332092.66heart T-16.277101206heart (T-14) non-29422438.65877.30heart T-142.631531586obstructive DCMheart (T-3399) DCM29426634.061268.12heart T-33993.803827464adenoid GW99-26926162285.91571.82adenoidtonsil GW98-28022582912.431824.86tonsilT cells PC00314284532710.375420.74T cellsPBMNC KC53.9353.93PBMNCmonocyte KC97.03194.06monocyteB cells PC00665284552096.554193.10B cellsdendritic cells 28441307.67615.34dendritic cellsneutrophils28440352.93352.93neutrophilseosinophils28446148.18296.36eosinophilsBM unstim KC44.6244.62BM unstimBM stim KC102.28102.28BM stim2.29224563osteo dif KC13.1713.17osteo difosteo undif KC9.049.04osteo undif−1.456858407chondrocytes189.54473.85chondrocytesOA Synovium IP12/01294629850.719850.71OA SynoviumOA Synovium NP10/01294614627.579255.14OA SynoviumOA Synovium NP57/00284643568.617137.22OA SynoviumRA Synovium NP03/01284664452.778905.54RA SynoviumRA Synovium NP71/00284674479.748959.48RA SynoviumRA Synovium NP45/002847510746.7321493.46RA SynoviumOA bone (biobank)29217468.68468.68OA bone(biobank)OA bone Sample 1J. Emory2277.54555.00OA boneOA bone Sample 2J. Emory921.911843.82OA boneCartilage (pool)Normal9515.6119031.22Cartilage (pool)Cartilage (pool)OA3862.557725.10Cartilage (pool)−2.463556459PBL unifected284412689.775379.54PBL unifectedPBL HIV IIIB284421110.92221.80PBL HIV IIIB−2.421253038MRC5 uninfected (100%)29158163.61327.22MRC5uninfected(100%)MRC5 HSV strain F2917835.9471.88MRC5 HSV−4.552309405strain FW12 cells29179171.69343.38W12 cellsKeratinocytes29180142.68285.36Keratinocytes

[0130] Gene Name SBh511827.C1q-related factor

12Fold Change in DiseasePopulation Relative toDisease tissuesNormalcolon tumor1.10colon tumor4.92colon tumor−2.43colon tumor−2.75lung tumor−5.06lung tumor1.05lung tumor2.57lung tumor−2.14breast tumor2.29breast tumor1.76breast tumor5.36breast tumor1.91brain stage 5 ALZ−3.18brain stage 5 ALZ1.75brain stage 5 ALZ1.14brain stage 5 ALZ1.17lung 24−15.69lung 28−6.58lung 23−2.88asthmatic lung−1.36asthmatic lung2.53asthmatic lung6.22asthmatic lung1.97endo VEGF7.25endo bFGF1.03heart T-16.28heart T-142.63heart T-33993.80BM stim2.29osteo undif−1.46Cartilage (pool)−2.46PBL HIV IIIB−2.42MRC5 HSV strain F−4.55

[0131] Gene Name sbg533677PALSa

[0132] Expression in immune cells with corroborating expression in asthmatic lung (¾) suggesting possible role in Asthma. Overexpressed in heart disease suggesting role in CV diseases. Down regulation in HSV infection suggesting possible host cell factor. High brain expression in whole brain and cortex but does not correlate with Alzheimer's disease.

13copies ofmRNAdetected/Mean GOIMean GOIAverage50 ng/50 ngSamplecopiescopiesGOI18S rRNA18S rRNAtotalsbg533677PALSa(sample 1)(sample 2)Copies(ng)(ng)RNASubcutaneous51.4492.6472.043.0616.341177.12Adipocytes ZenbioSubcutaneous Adipose5.242.423.830.9652.36200.52ZenbioAdrenal Gland Clontech8.539.108.820.6181.97722.54Whole Brain Clontech15161.4515339.8815250.677.246.91105322.27Fetal Brain Clontech18.1723.2220.700.48103.952151.25Cerebellum Clontech219.5945.25132.422.1723.043051.15Cervix122.0191.28106.652.4220.662203.41Colon267.14172.02219.582.7118.454051.29Endometrium18.2234.0326.130.7368.211782.06Esophagus45.2346.4345.831.3736.501672.63Heart Clontech27.2252.9140.071.3237.881517.61Hypothalamus1.282.121.700.32155.28263.98Ileum94.43111.58103.012.5819.381996.22Jejunum1633.122127.361880.246.607.5814244.24Kidney63.84160.51112.182.1223.582645.64Liver29.4242.0335.731.5033.331190.83Fetal Liver Clontech2536.602105.612321.1110.404.8111159.16Lung136.03198.77167.402.5719.463256.81Mammary Gland424.73623.88524.3113.003.852016.56ClontechMyometrium49.18119.8384.512.3421.371805.66Omentum133.77211.60172.693.9412.692191.43Ovary137.22102.84120.034.3411.521382.83Pancreas24.0319.4621.750.8161.801343.94Head of Pancreas15.989.7012.841.5731.85408.92Parotid Gland164.01243.65203.835.489.121859.76Placenta Clontech443.13418.73430.935.269.514096.29Prostate348.7883.31216.053.0016.673600.75Rectum82.65132.21107.431.2340.654367.07Salivary Gland194.49469.68332.097.316.842271.44ClontechSkeletal Muscle32.5169.1450.831.2639.682016.87ClontechSkin8.9455.3832.161.2141.321328.93Small Intestine4.5020.2112.360.9851.07631.00ClontechSpleen115.4295.13105.284.9210.161069.87Stomach58.96147.19103.082.7318.321887.82Testis Clontech28.256.4217.340.5787.871523.29Thymus Clontech1685.231168.511426.879.895.067213.70Thyroid215.93210.84213.392.7718.053851.71Trachea Clontech195.46204.92200.199.715.151030.84Urinary Bladder238.82321.83280.335.479.142562.39Uterus162.57183.68173.135.349.361621.02copies ofRegmRNAnumberMeandetected/50 ngFold ChangeSample(GSKGOItotalin Diseasesbg533677PALSaidentifier)copiesRNASamplePopulationcolon normal GW98-167219413216.526433.04colon normalcolon tumor GW98-166219402713.615427.22colon tumor−1.185328769colon normal GW98-17822080324.52649.04colon normalcolon tumor GW98-17722060657.51315.00colon tumor2.026069272colon normal GW98-561235142007.124014.24colon normalcolon tumor GW98-560235131433.272866.54colon tumor−1.400378156colon normal GW98-894246915207.1110414.22colon normalcolon tumor GW98-893246903315.886631.76colon tumor−1.570355381lung normal GW98-3207422880.65761.20lung normallung tumor GW98-220741729.251458.50lung tumor−3.950085704lung normal GW97-179206772554.175108.34lung normallung tumor GW97-178206763737.047474.08lung tumor1.463113262lung normal GW98-165219225054.410108.80lung normallung tumor GW98-164219212226.274452.54lung tumor−2.270344567lung normal GW98-282225841861.663723.32lung normallung tumor GW98-281225831654.053308.10lung tumor−1.125516157breast normal GW00-392287501333.431333.43breast normalbreast tumor GW00-391287461994.933989.86breast tumor2.992178067breast normal GW00-41328798860.05860.05breast normalbreast tumor GW00-412287972402.764805.52breast tumor5.587489099breast normal GW00-27592-95430.22430.22breast normal235: 238breast tumor GW00-27588-911888.171888.17breast tumor4.388847566231: 234breast normal GW98-621236563330.566661.12breast normalbreast tumor GW98-620236551697.993395.98breast tumor−1.961472093brain normal BB99-5422550711126.0722252.14brain normalbrain normal BB99-406255091059721194.00brain normalbrain normal BB99-904255465508.0611016.12brain normalbrain stage 5 ALZ BB99-255022411.634823.26brain stage 5−3.763862339874ALZbrain stage 5 ALZ BB99-2550310009.7520019.50brain stage 51.102754458887ALZbrain stage 5 ALZ BB99-255046223.9312447.86brain stage 5−1.458410254862ALZbrain stage 5 ALZ BB99-255426282.0212564.04brain stage 5−1.444924297927ALZCT lung KCnormal824.221648.44CT lunglung 26 KCnormal460.62460.62lung 26lung 27 KCnormal256.02256.02lung 27lung 24 KCCOPD218.84218.84lung 24−3.806159751lung 28 KCCOPD382.73382.73lung 28−2.176312283lung 23 KCCOPD251.06251.06lung 23−3.317692982lung 25 KCCOPD966.68966.68lung 25asthmatic lung293211431.161431.16asthmatic lung1.718202992ODO3112asthmatic lung293233337.626675.24asthmatic lung8.014070641ODO3433asthmatic lung2932210770.4221540.84asthmatic lung25.86121449ODO3397asthmatic lung293254890.899781.78asthmatic lung11.74367902ODO4928endo cells KCcontrol379.58379.58endo cellsendo VEGF KC308.3308.30endo VEGF−1.231203373endo bFGF KC292.91292.91endo bFGF−1.295892936heart Clontechnormal189.25378.50heartheart (T-1) ischemic294173974.327948.64heart T-121.00036988heart (T-14) non-294222874.835749.66heart T-1415.19064729obstructive DCMheart (T-3399) DCM294263931.977863.94heart T-339920.77659181adenoid GW99-26926162960.031920.06adenoidtonsil GW98-280225822921.825843.64tonsilT cells PC00314284534357.568715.12T cellsPBMNC KC92.9392.93PBMNCmonocyte KC109.26218.52monocyteB cells PC00665284552927.245854.48B cellsdendritic cells 284413972.137944.26dendritic cellsneutrophils284401995.661995.66neutrophilseosinophils284463370.636741.26eosinophilsBM unstim KC219.27219.27BM unstimBM stim KC305.59305.59BM stim1.393669905osteo dif KC1240.851240.85osteo difosteo undif KC250250.00osteo undif−4.9634chondrocytes1932.64831.50chondrocytesOA Synovium IP12/01294621711.571711.57OA SynoviumOA Synovium NP10/01294611029.72059.40OA SynoviumOA Synovium NP57/00284642112.514225.02OA SynoviumRA Synovium NP03/01284662679.385358.76RA SynoviumRA Synovium NP71/00284672419.694839.38RA SynoviumRA Synovium NP45/00284752917.735835.46RA SynoviumOA bone (biobank)29217254.63254.63OA bone(biobank)OA bone Sample 1J. Emory2069.384138.76OA boneOA bone Sample 2J. Emory1115.32230.60OA boneCartilage (pool)Normal3174.676349.34Cartilage(pool)Cartilage (pool)OA1272.392544.78Cartilage−2.495044758(pool)PBL unifected284414083.148166.28PBL unifectedPBL HIV IIIB284421715.443430.88PBL HIV IIIB−2.380228979MRC5 uninfected291586381.9512763.90MRC5(100%)uninfected(100%)MRC5 HSV strain F29178759.861519.72MRC5 HSV−8.398849788strain FW12 cells291794256.488512.96W12 cellsKeratinocytes291807993.7415987.48Keratinocytes

[0133] Gene Name sbg533677PALSa

14Fold Change in DiseasePopulation Relative toDisease tissuesNormalcolon tumor−1.19colon tumor2.03colon tumor−1.40colon tumor−1.57lung tumor−3.95lung tumor1.46lung tumor−2.27lung tumor−1.13breast tumor2.99breast tumor5.59breast tumor4.39breast tumor−1.96brain stage 5 ALZ−3.76brain stage 5 ALZ1.10brain stage 5 ALZ−1.46brain stage 5 ALZ−1.44lung 24−3.81lung 28−2.18lung 23−3.32asthmatic lung1.72asthmatic lung8.01asthmatic lung25.86asthmatic lung11.74endo VEGF−1.23endobFGF−1.30heart T-121.00heart T-1415.19heart T-339920.78BM stim1.39osteo undif−4.96Cartilage (pool)−2.50PBL HIV IIIB−2.38MRC5 HSV strain F−8.40

[0134] Gene Name sbg535067MELAa

[0135] Highest expression in brain (unchanged in alzheimers), fetal liver, and thymus. Downregulated in COPD diseased lung suggesting involvement in this disease. Expression in spleen, T and B cells, neutrophils, and chondrocytes corroborates expression in OA and RA synovium suggesting involvement with OA and RA disease. Upregulated in 3 of 4 asthmatic lung suggesting involvement in asthma. GI tract expression could suggest claims for IBS, IBD, and Crohns disease.

15copies ofmRNAMean GOIMean GOIAverage50 ng/detected/50 ngSamplecopiescopiesGOI18S rRNA18SrRNAtotalsbg535067MELAa(sample 1)(sample 2)Copies(ng)(ng)RNASubcutaneous23.7419.9221.833.0616.34356.70Adipocytes ZenbioSubcutaneous Adipose15.73.589.640.9652.36504.71ZenbioAdrenal Gland Clontech1.190.430.810.6181.9766.39Whole Brain Clontech1924.362038.131981.257.246.9113682.63Fetal Brain Clontech000.000.48103.950.00Cerebellum Clontech2.165.793.982.1723.0491.59Cervix7.087.777.432.4220.66153.41Colon67.468.1967.802.7118.451250.83Endometrium4.183.423.800.7368.21259.21Esophagus15.0817.416.241.3736.50592.70Heart Clontech5.8614.3210.091.3237.88382.20Hypothalamus000.000.32155.280.00Ileum32.3466.9349.642.5819.38961.92Jejunum94.38105.0299.706.607.58755.30Kidney10.7730.9320.852.1223.58491.75Liver11.3710.2410.811.5033.33360.17Fetal Liver Clontech494.61735.39615.0010.404.812956.73Lung32.9233.7433.332.5719.46648.44Mammary Gland412.57499.72456.1513.003.851754.40ClontechMyometrium63.47115.6489.562.3421.371913.57Omentum10.7313.0311.883.9412.69150.76Ovary26.0920.4923.294.3411.52268.32Pancreas1.740.020.880.8161.8054.39Head of Pancreas3.261.922.591.5731.8582.48Parotid Gland19.2335.4127.325.489.12249.27Placenta Clontech117.8116.55117.185.269.511113.83Prostate10.111.886.003.0016.6799.92Rectum8.48.818.611.2340.65349.80Salivary Gland26.7614.9620.867.316.84142.68ClontechSkeletal Muscle6.7103.361.2639.68133.13ClontechSkin11.6524.9418.301.2141.32755.99Small Intestine6.3211.138.730.9851.07445.61ClontechSpleen173.46142.39157.934.9210.161604.93Stomach6.6414.310.472.7318.32191.76Testis Clontech8.484.716.600.5787.87579.53Thymus Clontech544.9734.52639.719.895.063234.13Thyroid8.812.525.672.7718.05102.26Trachea Clontech84.46104.0994.289.715.15485.45Urinary Bladder17.4727.2422.365.479.14204.34Uterus40.0546.4943.275.349.36405.15copies ofRegmRNAnumberMeandetected/50 ngFold ChangeSample(GSKGOItotalin Diseasesbg535067MELAaidentifier)copiesRNASamplePopulationcolon normal GW98-16721941614.521229.04colon normalcolon tumor GW98-16621940809.881619.76colon tumor1.32colon normal GW98-17822080339.76679.52colon normalcolon tumor GW98-17722060104.5209.00colon tumor−3.25colon normal GW98-56123514235.88471.76colon normalcolon tumor GW98-5602351393.21186.42colon tumor−2.53colon normal GW98-89424691309.33618.66colon normalcolon tumor GW98-89324690218.62437.24colon tumor−1.41lung normal GW98-320742558.131116.26lung normallung tumor GW98-22074182.81165.62lung tumor−6.74lung normal GW97-179206772066.154132.30lung normallung tumor GW97-17820676859.791719.58lung tumor−2.40lung normal GW98-16521922574.921149.84lung normallung tumor GW98-16421921845.891691.78lung tumor1.47lung normal GW98-28222584210.81421.62lung normallung tumor GW98-28122583346.75693.50lung tumor1.64breast normal GW00-392287501165.851165.85breast normalbreast tumor GW00-39128746728.171456.34breast tumor1.25breast normal GW00-41328798836.13836.13breast normalbreast tumor GW00-41228797591.761183.52breast tumor1.42breast normal GW00-27592-95415.79415.79breast normal235: 238breast tumor GW00-27588-911193.031193.03breast tumor2.87231: 234breast normal GW98-621236561070.752141.50breast normalbreast tumor GW98-620236551904.413808.82breast tumor1.78brain normal BB99-5422550722658.6345317.26brain normalbrain normal BB99-406255094463.728927.44brain normalbrain normal BB99-904255466799.4913598.98brain normalbrain stage 5 ALZ BB99-25502449.53899.06brain stage 5−25.15874ALZbrain stages 5 ALZ BB99-255036199.1112398.22brain stage 5−1.82887ALZbrain stage 5 ALZ BB99-255044621.769243.52brain stages 5−2.45862ALZbrain stage 5 ALZ BB99-255424859.749719.48brain stages 5−2.33927ALZCT lung KCnormal527.051054.10CT lunglung 26 KCnormal628.91628.91lung 26lung 27 KCnormal66.7866.78lung 27lung 24 KCCOPD45.1345.13lung 24−9.96lung 28 KCCOPD64.164.10lung 28−7.01lung 23 KCCOPD97.6197.61lung 23−4.61lung 25 KCnormal48.6948.69lung 25asthmatic lung29321521.43521.43asthmatic lung1.16ODO3112asthmatic lung293231614.293228.58asthmatic lung7.18ODO3433asthmatic lung293222352.954705.90asthmatic lung10.47ODO3397asthmatic lung293251560.63121.20asthmatic lung6.94ODO4928endo cells KCcontrol187.93187.93endo cellsendo VEGF KC30.6530.65endo VEGF−6.13endo bFGF KC93.3293.32endo bFGF−2.01heart Clontechnormal585.461170.92heartheart (T-1) ischemic294171546.853093.70heart T-12.64heart(T-14) non-294221304.672609.34heart T-142.23obstructive DCMheart (T-3399) DCM294262208.724417.44heart T-33993.77adenoid GW99-26926162896.421792.84adenoidtonsil GW98-280225822459.554919.10tonsilT cells PC00314284532147.554295.10T cellsPBMNC KC143.16143.16PBMNCmonocyte KC135.21270.42monocyteB cells PC00665284551305.962611.92B cellsdendritic cells 28441118.25236.50dendritic cellsneutrophils28440960.88960.88neutrophilseosinophils2844614.3128.62eosinophilsBM unstim KC132.56132.56BM unstimBM stim KC31.2731.27BM stim−4.24osteo dif KC127.45127.45osteo dif2.02osteo undif KC63.0763.07osteo undifchondrocytes771.651929.13chondrocytesOA Synovium IP12/01294622214.82214.80OA SynoviumOA Synovium NP10/0129461576.671153.34OA SynoviumOA Synovium NP57/0028464682.061364.12OA SynoviumRA Synovium NP03/0128466499.99999.98RA SynoviumRA Synovium NP71/0028467631.411262.82RA SynoviumRA Synovium NP45/0028475551.21102.40RA SynoviumOA bone (biobank)29217224.68224.68OA bone(biobank)OA bone Sample 1J. Emory751.771503.54OA boneOA bone Sample 2J. Emory633.331266.66OA boneCartilage (pool)Normal1863.023726.04Cartilage(pool)Cartilage (pool)OA1658.13316.20Cartilage−1.12(pool)PBL unifected284414666.529333.04PBL unifectedPBL HIV IIIB284422342.794685.58PBL HIV IIIB−1.99MRC5 uninfected29158951.751903.50MRC5(100%)uninfected(100%)MRC5 HSV strain F2917800.00MRC5 HSV−1903.50strain FW12 cells291792071.684143.36W12 cellsKeratinocytes291803752.887505.76Keratinocytes

[0136] Gene Name sbg535067MELAa

16Fold Change in DiseasePopulation Relative toDisease tissuesNormalcolon tumor1.32colon tumor−3.25colon tumor−2.53colon tumor−1.41lung tumor−6.74lung tumor−2.40lung tumor1.47lung tumor1.64breast tumor1.25breast tumor1.42breast tumor2.87breast tumor1.78brain stage 5 ALZ−25.15brain stage 5 ALZ−1.82brain stage 5 ALZ−2.45brain stage 5 ALZ−2.33lung 24−9.96lung 28−7.01lung 23−4.61asthmatic lung1.16asthmatic lung7.18asthmatic lung10.47asthmatic lung6.94endo VEGF−6.13endo bFGF−2.01heart T-12.64heart T-142.23heart T-33993.77BM stim−4.24osteo dif2.02Cartilage (pool)−1.12PBL HIV IIIB−1.99MRC5 HSV strain F−1903.50

[0137] Gene Name sbg590979THP

[0138] High in fetal liver and some expression in adult liver. Expressed in adult and fetal brain. Hypothalamus is a significant fraction of the brain expression suggesting metabolic disease claims related to diabetes, impaired glucose tolerance, metabolic syndrome, and obesity. Significant overexpression in one breast cancer is sufficient for claim in this area (caveat: lack of expression in normal may lead to exaggerated fold-overexpression). Decreased expression in dilated cardiomyopathy suggests involvement in this disease. Expression in OA and RA synovium and corroborating expression in immune cells (adenoid, tonsil, T, B, and eosinophils) suggests involvement in both RA and OA disease. Significant decrease in DCM heart suggests involvement in dilated cardiomyopathy.

17copiesofmRNAdetected/Mean GOIMean GOIAverage50 ng/50 ngSamplecopiescopiesGOI18S rRNA18S rRNAtotalsbg590979THP(sample 1)(sample 2)Copies(ng)(ng)RNASubcutaneous000.003.0616.340.00Adipocytes ZenbioSubcutaneous Adipose000.000.9652.360.00ZenbioAdrenal Gland Clontech000.000.6181.970.00Whole Brain Clontech103.1792.0297.607.246.91674.00Fetal Brain Clontech05.322.660.48103.95276.51Cerebellum Clontech000.002.1723.040.00Cervix000.002.4220.660.00Colon5.584.455.022.7118.4592.53Endometrium000.000.7368.210.00Esophagus000.001.3736.500.00Heart Clontech04.112.061.3237.8877.84Hypothalamus4.1602.080.32155.28322.98Ileum07.163.582.5819.3869.38Jejunum3.158.345.756.607.5843.52Kidney000.002.1223.580.00Liver17.829.9523.881.5033.33795.83Fetal Liver Clontech2349.792396.712373.2510.404.8111409.86Lung9.7504.882.5719.4694.84Mammary Gland000.0013.003.850.00ClontechMyometrium000.002.3421.370.00Omentum000.003.9412.690.00Ovary12.6421.8517.254.3411.52198.68Pancreas000.000.8161.800.00Head of Pancreas000.001.5731.850.00Parotid Gland17.6408.825.489.1280.47Placenta Clontech2.6601.335.269.5112.64Prostate000.003.0016.670.00Rectum000.001.2340.650.00Salivary Gland Clontech3.5801.797.316.8412.24Skeletal Muscle Clontech000.001.2639.680.00Skin000.001.2141.320.00Small Intestine Clontech000.000.9851.070.00Spleen14.0113.813.914.9210.16141.31Stomach000.002.7318.320.00Testis Clontech000.000.5787.870.00Thymus Clontech013.246.629.895.0633.47Thyroid10.5305.272.7718.0595.04Trachea Clontech09.34.659.715.1523.94Urinary Bladder000.005.479.140.00Uterus13.936.4310.185.349.3695.32copies ofRegmRNAFoldnumberMeandetected/50 ngChange inSample(GSKGOItotalDiseasesbg590979THPidentifier)copiesRNASamplePopulationcolon normal GW98-16721941148.83297.66colon normalcolon tumor GW98-16621940246.62493.24colon tumor1.66colon normal GW98-1782208097.46194.92colon normalcolon tumor GW98-1772206068.77137.54colon tumor−1.42colon normal GW98-56123514210.78421.56colon normalcolon tumor GW98-5602351376.83153.66colon tumor−2.74colon normal GW98-89424691130.52261.04colon normalcolon tumor GW98-8932469089.49178.98colon tumor−1.46lung normal GW98-320742108.75217.50lung normallung tumor GW98-2207419.9419.88lung tumor−10.94lung normal GW97-1792067739.3778.74lung normallung tumor GW97-1782067634.8469.68lung tumor−1.13lung normal GW98-1652192254.25108.50lung normallung tumor GW98-16421921153.78307.56lung tumor2.83lung normal GW98-2822258461.06122.12lung normallung tumor GW98-2812258342.2284.44lung tumor−1.45breast normal GW00-3922875023.6423.64breast normalbreast tumor GW00-3912874624.5449.08breast tumor2.08breast normal GW00-4132879800.00breast normalbreast tumor GW00-4122879719.5539.10breast tumor39.10breast normal GW00-27592-9500.00breast normal235: 238breast tumor GW00-27588-9100.00breast tumor0.00231: 234breast normal GW98-6212365618.1836.36breast normalbreast tumor GW98-6202365578.46156.92breast tumor4.32brain normal BB99-5422550731.5163.02brain normalbrain normal BB99-4062550939.5579.10brain normalbrain normal BB99-904255463.647.28brain normalbrain stage 5 ALZ BB99-2550225.8451.68brain stage 51.04874ALZbrain stages 5 ALZ BB99-2550398.79197.58brain stages 53.97887ALZbrain stage 5 ALZ BB99-2550443.2786.54brain stage 51.74862ALZbrain stage 5 ALZ BB99-2554256.03112.06brain stage 52.25927ALZCT lung KCnormal7.5915.18CT lunglung 26 KCnormal00.00lung 26lung 27 KCnormal00.00lung 27lung 24 KCCOPD00.00lung 24−3.80lung 28 KCCOPD00.00lung 28−3.80lung 23 KCCOPD3.413.41lung 23−1.11lung 25 KCnormal00.00lung 25asthmatic lung ODO31122932100.00asthmatic lung−3.80asthmatic lung ODO343329323714.00asthmatic lung3.69asthmatic lung ODO33972932214.3328.66asthmatic lung7.55asthmatic lung ODO4928293257.8115.62asthmatic lung4.12endo cells KCcontrol00.00endo cellsendoVEGF KC2.172.17endo VEGF2.17endo bFGF KC00.00endo bFGF0.00heart Clontechnormal58.56117.12heartheart (T-1) ischemic2941740.5981.18heart T-1−1.44heart (T-14) non-29422180.2360.40heart T-143.08obstructive DCMheart (T-3399) DCM2942600.00heart T-3399−117.12adenoid GW99-2692616225.3850.76adenoidtonsil GW98-2802258231.1962.38tonsilT cells PC003142845325.2450.48T cellsPBMNC KC00.00PBMNCmonocyte KC1.432.86monocyteB cells PC006652845520.9141.82B cellsdendritic cells 2844100.00dendritic cellsneutrophils2844020.8820.88neutrophilseosinophils2844631.7363.46eosinophilsBM unstim KC00.00BM unstimBM stim KC9.99.90BM stim9.90osteo dif KC3.623.62osteo dif3.62osteo undif KC00.00osteo undifchondrocytes26.1465.35chondrocytesOA Synovium IP12/012946225.6425.64OA SynoviumOA Synovium NP10/012946152104.00OA SynoviumOA Synovium NP57/002846490.32180.64OA SynoviumRA Synovium NP03/012846664.83129.66RA SynoviumRA Synovium NP71/0028467321.14642.28RA SynoviumRA Synovium NP45/002847591.05182.10RA SynoviumOA bone (biobank)2921710.5810.58OA bone(biobank)OA bone Sample 1J. Emory41.4682.92OA boneOA bone Sample 2J. Emory82164.00OA boneCartilage (pool)Normal12.7225.44Cartilage (pool)Cartilage (pool)OA45.4590.90Cartilage (pool)3.57PBL unifected2844118.3236.64PBL unifectedPBL HIV IIIB2844246.3892.76PBL HIV IIIB2.53MRC5 uninfected (100%)2915810.1720.34MRC5uninfected(100%)MRC5 HSV strain F29178424.91849.82MRC5 HSV41.78strain FW12 cells2917912.3524.70W12 cellsKeratinocytes2918011.7423.48Keratinocytes

[0139] Gene Name sbg590979THP

18Fold Change in DiseasePopulation Relative toDisease tissuesNormalcolon tumor1.66colon tumor−1.42colon tumor−2.74colon tumor−1.46lung tumor−10.94lung tumor−1.13lung tumor2.83lung tumor−1.45breast tumor2.08breast tumor39.10breast tumor0.00breast tumor4.32brain stage 5 ALZ1.04brain stage 5 ALZ3.97brain stage 5 ALZ1.74brain stage 5 ALZ2.25lung 24−3.80lung 28−3.80lung 23−1.11asthmatic lung−3.80asthmatic lung3.69asthmatic lung7.55asthmatic lung4.12endo VEGF2.17endo bFGF0.00heart T-1−1.44heart T-143.08heart T-3399−117.12BM stim9.90osteo dif3.62Cartilage (pool)3.57PBL HIV IIIB2.53MRC5 HSV strain F41.78

[0140] Gene Name sbg658629CRF

[0141] Highly expressed in brain. Expression in parotid gland suggest it is secreted.

[0142] Expression in chondrocyte cells consistent with expression in cartilage.

[0143] Downregulated in HSV infected MRC5 cells suggesting possible host factor for HSV infection.

19copies ofmRNAdetected/Mean GOIMean GOIAverage18S50 ng/18S50 ngSamplecopiescopiesGOIrRNArRNAtotalsbg658629CRF(sample 1)(sample 2)Copies(ng)(ng)RNASubcutaneous0.410.120.273.0616.344.33Adipocytes ZenbioSubcutaneous Adipose0.2600.130.9652.366.81ZenbioAdrenal Gland Clontech00.040.020.6181.971.64Whole Brain Clontech8417.59519.498968.507.246.9161937.12Fetal Brain Clontech8.610.039.320.48103.95968.30Cerebellum Clontech12.1112.112.112.1723.04278.92Cervix2.835.554.192.4220.6686.57Colon4.921.313.122.7118.4557.47Endometrium5.149.687.410.7368.21505.46Esophagus0.110.140.131.3736.504.56Heart Clontech01.030.521.3237.8819.51Hypothalamus00.270.140.32155.2820.96Ileum3.591.42.502.5819.3848.35Jejunum20.0731.0625.576.607.58193.67Kidney2.837.945.392.1223.58127.00Liver4.237.956.091.5033.33203.00Fetal Liver Clontech16.6625.8821.2710.404.81102.26Lung1.421.641.532.5719.4629.77Mammary Gland3.19.566.3313.003.8524.35ClontechMyometrium2.873.052.962.3421.3763.25Omentum2.763.53.133.9412.6939.72Ovary9.4310.7410.094.3411.52116.19Pancreas0.880.040.460.8161.8028.43Head of Pancreas0.040.120.081.5731.852.55Parotid Gland368.36439.47403.925.489.123685.36Placenta Clontech2.990.931.965.269.5118.63Prostate0.150.060.113.0016.671.75Rectum1.081.781.431.2340.6558.13Salivary Gland Clontech0.761.351.067.316.847.22Skeletal Muscle Clontech0.20.070.141.2639.685.36Skin0.030.050.041.2141.321.65Small Intestine Clontech7.10.033.570.9851.07182.07Spleen2.30.031.234.9210.1612.45Stomach3.634.64.122.7318.3275.37Testis Clontech8.574.186.380.5787.87560.19Thymus Clontech5.5416.0210.789.895.0654.50Thyroid12.124.348.232.7718.05148.56Trachea Clontech3.9717.7510.869.715.1555.92Urinary Bladder5.088.596.845.479.1462.48Uterus24.1629.4626.815.349.36251.03copies ofRegmRNAFoldnumberMeandetected/50 ngChangeSample(GSKGOItotalin Diseasesbg658629CRFidentifier)copiesRNASamplePopulationcolon normal GW98-16721941758.11516.20colon normalcolon tumor GW98-1662194077.72155.44colon tumor−9.75colon normal GW98-17822080364.17728.34colon normalcolon tumor GW98-1772206085.55171.10colon tumor−4.26colon normal GW98-56123514227.04454.08colon normalcolon tumor GW98-56023513294.95589.90colon tumor1.30colon normal GW98-89424691521.041042.08colon normalcolon tumor GW98-89324690194.26388.52colon tumor−2.68lung normal GW98-32074286.31172.62lung normallung tumor GW98-220741158.3316.60lung tumor1.83lung normal GW97-179206773312.46624.80lung normallung tumor GW97-1782067627.855.60lung tumor−119.15lung normal GW98-1652192217.5835.16lung normallung tumor GW98-1642192156.57113.14lung tumor3.22lung normal GW98-2822258448.6697.32lung normallung tumor GW98-2812258330.4360.86lung tumor−1.60breast normal GW00-39228750226.72226.72breast normalbreast tumor GW00-39128746181.98363.96breast tumor1.61breast normal GW00-4132879884.6684.66breast normalbreast tumor GW00-4122879743.2786.54breast tumor1.02breast normal GW00-27592-95266.41266.41breast normal235: 238breast tumor GW00-27588-9171.9971.99breast tumor−3.70231: 234breast normal GW98-62123656167.13334.26breast normalbreast tumor GW98-6202365563.98127.96breast tumor−2.61brain normal BB99-542255072057.454114.90brain normalbrain normal BB99-406255091914.413828.82brain normalbrain normal BB99-904255461209.142418.28brain normalbrain stage 5 ALZ BB99-255021126.822253.64brain stage 5−1.53874ALZbrain stage 5 ALZ BB99-255034130.768261.52brain stage 52.39887ALZbrain stage 5 ALZ BB99-255043025.266050.52brain stage 51.75862ALZbrain stage 5 ALZ BB99-255421582.923165.84brain stage 5−1.09927ALZCT lung KCnormal26.4952.98CT lunglung 26 KCnormal10.8510.85lung 26lung 27 KCnormal00.00lung 27lung 24 KCCOPD00.00lung 24−16.04lung 28 KCCOPD0.740.74lung 28−21.68lung 23 KCCOPD00.00lung 23−16.04lung 25 KCnormal0.330.33lung 25asthmatic lung ODO3112293215.955.95asthmatic lung−2.70asthmatic lung ODO34332932316.3332.66asthmatic lung2.04asthmatic lung ODO33972932225.2650.52asthmatic lung3.15asthmatic lung ODO49282932520.7841.56asthmatic lung2.59endo cells KCcontrol15.5515.55endo cellsendo VEGF KC6.356.35endo VEGF−2.45endo bFGF KC19.1619.16endo bFGF1.23heart Clontechnormal312.58625.16heartheart (T-1) ischemic29417107.41214.82heart T-1−2.91heart (T-14) non-2942265.45130.90heart T-14−4.78obstructive DCMheart (T-3399) DCM2942680.9161.80heart T-3399−3.86adenoid GW99-2692616211.4222.84adenoidtonsil GW98-2802258258.08116.16tonsilT cells PC003142845313.3126.62T cellsPBMNC KC0.180.18PBMNCmonocyte KC0.450.90monocyteB cells PC00665284552.474.94B cellsdendritic cells 2844119.5839.16dendritic cellsneutrophils284404.524.52neutrophilseosinophils284467.4114.82eosinophilsBM unstim KC00.00BM unstimBM stim KC8.978.97BM stim8.97osteo dif KC0.560.56osteo dif−1.43osteo undif KC0.80.80osteo undifchondrocytes547.41368.50chondrocytesOA Synovium IP12/0129462157.16157.16OA SynoviumOA Synovium NP10/012946146.0992.18OA SynoviumOA Synovium NP57/002846463.76127.52OA SynoviumRA Synovium NP03/012846664.6129.20RA SynoviumRA Synovium NP71/0028467200.22400.44RA SynoviumRA Synovium NP45/0028475189.2378.40RA SynoviumOA bone (biobank)2921734.7634.76OA bone(biobank)OA bone Sample 1J. Emory114.88229.76OA boneOA bone Sample 2J. Emory34.9369.86OA boneCartilage (pool)Normal750.071500.14Cartilage(pool)Cartilage (pool)OA107.9215.80Cartilage−6.95(pool)PBL unifected28441196.14392.28PBL unifectedPBL HIV IIIB28442120.64241.28PBL HIV IIIB−1.63MRC5 uninfected291581065.062130.12MRC5(100%)uninfected(100%)MRC5 HSV strain F29178179.4358.80MRC5 HSV−5.94strain FW12 cells29179127.4254.80W12 cellsKeratinocytes2918092.44184.88Keratinocytes

[0144] Gene Name sbg658629CRF

20Fold Change in DiseasePopulation Relative toDisease tissuesNormalcolon tumor−9.75colon tumor−4.26colon tumor1.30colon tumor−2.68lung tumor1.83lung tumor−119.15lung tumor3.22lung tumor−1.60breast tumor1.61breast tumor1.02breast tumor−3.70breast tumor−2.61brain stage 5 ALZ−1.53brain stage 5 ALZ2.39brain stage 5 ALZ1.75brain stage 5 ALZ−1.09lung 24−16.04lung 28−21.68lung 23−16.04asthmatic lung−2.70asthmatic lung2.04asthmatic lung3.15asthmatic lung2.59endo VEGF−2.45endo bFGF1.23heart T-1−2.91heart T-14−4.78heart T-3399−3.86BM stim8.97osteo dif−1.43Cartilage (pool)−6.95PBL HIV IIIB−1.63MRC5 HSV strain F−5.94

[0145] Gene Name sbg507131mannosidase

[0146] Expressed in brain,especially cortex, but not changed in alzheimers. Expressed in subcutaneous adipose and adipocytes. Expression in fetal liver, thymus, and immune cell populations (adenoid, tonsil, eosinophils, neutrophils, T cells, B cells, and dendritic cells) suggest some involvement in immune cell functions. Expression in asthmatic lung although not signficantly upregulated compared to clonetech pool. Expressed in OA and RA synovium, OA bone, cartilage, and chondrocytes suggests involvement in OA and RA. Significantly downregulated in HSV lung cell line suggests possbile host factor for HSV infection. Expression in subcutaneous adipose suggests claim for dyslipidemia and obesity.

21copies ofMeanmRNAGOI50 ng/detected/copiesMean GOIAverage18S18S50 ngSample(samplecopiesGOIrRNArRNAtotalsbg507131mannosidase1)(sample 2)Copies(ng)(ng)RNASubcutaneous157.3180.21168.763.0616.342757.43Adipocytes ZenbioSubcutaneous Adipose27.087.0817.080.9652.36894.24ZenbioAdrenal Gland Clontech000.000.6181.970.00Whole Brain Clontech8341.4412017.6510179.557.246.9170300.73Fetal Brain Clontech11.4815.8513.670.48103.951420.48Cerebellum Clontech10.539.039.782.1723.04225.35Cervix23.611.5817.592.4220.66363.43Colon38.3172.5555.432.7118.451022.69Endometrium15.9921.6218.810.7368.211282.74Esophagus6.277.286.781.3736.50247.26Heart Clontech08.154.081.3237.88154.36Hypothalamus000.000.32155.280.00Ileum6.5811.078.832.5819.38171.03Jejunum38.7451.4345.096.607.58341.55Kidney20.726.6223.662.1223.58558.02Liver16.7415.4916.121.5033.33537.17Fetal Liver Clontech876.2881.14878.6710.404.814224.38Lung09.214.612.5719.4689.59Mammary Gland168.63218.21193.4213.003.85743.92ClontechMyometrium30.4512.6521.552.3421.37460.47Omentum10.9205.463.9412.6969.29Ovary78.2148.5263.374.3411.52730.01Pancreas0.830.380.610.8161.8037.39Head of Pancreas0.4500.231.5731.857.17Parotid Gland28.4886.1757.335.489.12523.04Placenta Clontech49.2492.6770.965.269.51674.48Prostate31.4122.6427.033.0016.67450.42Rectum27.3823.0125.201.2340.651024.19Salivary Gland Clontech64.8884.1974.547.316.84509.82Skeletal Muscle Clontech0.880.380.631.2639.6825.00Skin00.440.221.2141.329.09Small Intestine Clontech000.000.9851.070.00Spleen28.3210.1619.244.9210.16195.53Stomach0.4911.866.182.7318.32113.10Testis Clontech000.000.5787.870.00Thymus Clontech992.361311.321151.849.895.065823.26Thyroid5.2529.5117.382.7718.05313.72Trachea Clontech96.0282.5689.299.715.15459.78Urinary Bladder22.0534.4528.255.479.14258.23Uterus74.0295.4384.735.349.36793.31copies ofRegmRNAFoldnumberMeandetected/50 ngChange inSample(GSKGOItotalDiseasesbg507131mannosidaseidentifier)copiesRNASamplePopulationcolon normal GW98-167219419614.319228.60colon normalcolon tumor GW98-1662194016103.8732207.74colon tumor1.67colon normal GW98-178220802303.044606.08colon normalcolon tumor GW98-177220605088.2210176.44colon tumor2.21colon normal GW98-561235149405.1218810.24colon normalcolon tumor GW98-560235137410.9714821.94colon tumor−1.27colon normal GW98-8942469117796.0835592.16colon normalcolon tumor GW98-8932469011212.1222424.24colon tumor−1.59lung normal GW98-32074227285.154570.20lung normallung tumor GW98-2207414815.299630.58lung tumor−5.67lung normal GW97-1792067710640.7321281.46lung normallung tumor GW97-1782067613513.2327026.46lung tumor1.27lung normal GW98-165219229994.8219989.64lung normallung tumor GW98-1642192110116.1720232.34lung tumor1.01lung normal GW98-282225843301.076602.14lung normallung tumor GW98-281225834877.029754.04lung tumor1.48breast normal GW00-392287504720.464720.46breast normalbreast tumor GW00-391287464546.769093.52breast tumor1.93breast normal GW00-413287982621.822621.82breast normalbreast tumor GW00-412287976120.1412240.28breast tumor4.67breast normal GW00-27592-951687.451687.45breast normal235: 238breast tumor GW00-27588-915583.725583.72breast tumor3.31231: 234breast normal GW98-621236565377.7910755.58breast normalbreast tumor GW98-620236554502.239004.46breast tumor−1.19brain normal BB99-542255076715.6913431.38brain normalbrain normal BB99-406255095048.4310096.86brain normalbrain normal BB99-904255465145.0910290.18brain normalbrain stage 5 ALZ BB99-255022895.875791.74brain stage 5−1.95874ALZbrain stage 5 ALZ BB99-255037573.4115146.82brain stage 51.34887ALZbrain stage 5 ALZ BB99-255045549.1811098.36brain stage 5−1.02862ALZbrain stage 5 ALZ BB99-255427409.4314818.86brain stage 51.31927ALZCT lung KCnormal5550.2311100.46CT lunglung 26 KCnormal148.79148.79lung 26lung 27 KCnormal69.1369.13lung 27lung 24 KCCOPD85.0985.09lung 24−33.61lung 28 KCCOPD122.28122.28lung 28−23.39lung 23 KCCOPD83.0883.08lung 23−34.42lung 25 KCnormal121.14121.14lung 25asthmatic lung ODO3112293212772.082772.08asthmatic lung−1.03asthmatic lung ODO3433293234996.389992.76asthmatic lung3.49asthmatic lung ODO3397293229994.3819988.76asthmatic lung6.99asthmatic lung ODO4928293256018.9612037.92asthmatic lung4.21endo cells KCcontrol428.24428.24endo cellsendo VEGF KC535535.00endo VEGF1.25endo bFGF KC323.01323.01endo bFGF−1.33heart Clontechnormal2610.155220.30heartheart (T-1) ischemic294174004.998009.98heart T-11.53heart (T-14) non-294225596.9811193.96heart T-142.14obstructive DCMheart (T-3399) DCM294269381.5318763.06heart T-33993.59adenoid GW99-269261624435.488870.96adenoidtonsil GW98-280225827399.5314799.06tonsilT cells PC00314284536576.413152.80T cellsPBMNC KC139.42139.42PBMNCmonocyte KC126.02252.04monocyteB cells PC00665284559735.4219470.84B cellsdendritic cells 2844115293.6730587.34dendritic cellsneutrophils2844013487.0713487.07neutrophilseosinophils2844613111.4626222.92eosinophilsBM unstim KC332.7332.70BM unstimBM stim KC379.27379.27BM stim1.14osteo dif KC427.84427.84osteo dif1.60osteo undif KC267.96267.96osteo undifchondrocytes7063.5517658.88chondrocytesOA Synovium IP12/01294629069.179069.17OA SynoviumOA Synovium NP10/01294614247.368494.72OA SynoviumOA Synovium NP57/00284644826.099652.18OA SynoviumRA Synovium NP03/01284666003.3612006.72RA SynoviumRA Synovium NP71/00284676850.6213701.24RA SynoviumRA Synovium NP45/00284758737.5917475.18RA SynoviumOA bone (biobank)292173479.783479.78OA bone(biobank)OA bone Sample 1J. Emory2992.045984.08OA boneOA bone Sample 2J. Emory5164.1410328.28OA boneCartilage (pool)Normal7859.2815718.56Cartilage(pool)Cartilage (pool)OA4341.018682.02Cartilage−1.81(pool)PBL unifected2844116983.233966.40PBL unifectedPBL HIV IIIB284429427.0118854.02PBL HIV IIIB−1.80MRC5 uninfected2915817734.8535469.70MRC5(100%)uninfected(100%)MRC5 HSV strain F29178670.021340.04MRC5 HSV−26.47strain FW12 cells291793619.547239.08W12 cellsKeratinocytes291804955.739911.46Keratinocytes

[0147] Gene Name sbg507131mannosidase

22Fold Change in DiseasePopulation Relative toDisease tissuesNormalcolon tumor1.67colon tumor2.21colon tumor−1.27colon tumor−1.59lung tumor−5.67lung tumor1.27lung tumor1.01lung tumor1.48breast tumor1.93breast tumor4.67breast tumor3.31breast tumor−1.19brain stage 5 ALZ−1.95brain stage 5 ALZ1.34brain stage 5 ALZ−1.02brain stage 5 ALZ1.31lung 24−33.61lung 28−23.39lung 23−34.42asthmatic lung−1.03asthmatic lung3.49asthmatic lung6.99asthmatic lung4.21endo VEGF1.25endo bFGF−1.33heart T-11.53heart T-142.14heart T-33993.59BM stim1.14osteo dif1.60Cartilage (pool)−1.81PBL HIV IIIB−1.80MRC5 HSV strain F−26.47

[0148] Gene Name sbg655871calgizzarin-like

[0149] High expression in brain. Expression in intestines along with immune expression suggest claims for IBS, IBD, and crohn's disease. Fetal liver, thymus, adenoid, tonsil, T and B cells and monocytes corroborates immune cell expression. Expression in RA and OA synovium and OA bone suggests involvement in these diseases. Significant overexpression in one breast tumor is sufficient to claim breast cancer (caveat: undetectable expression in normal may lead to exaggerated fold-overexpression). Consistently higher expression in normal adjacent and tumor tissue compared to tissues on normal masterplate is also consistent with expression in activated immune cells.

23copiesofmRNAdetected/SampleMean GOIMean GOIAverage18 S50 ng/18 S50 ngsbg655871calgizzarin-copiescopiesGOIrRNArRNAtotallike(sample 1)(sample 2)Copies(ng)(ng)RNASubcutaneous000.003.0616.340.00Adipocytes ZenbioSubcutaneous Adipose000.000.9652.360.00ZenbioAdrenal Gland Clontech000.000.6181.970.00Whole Brain Clontech537.46799.45668.467.246.914616.40Fetal Brain Clontech000.000.48103.950.00Cerebellum Clontech29.913.6521.782.1723.04501.73Cervix000.002.4220.660.00Colon15.4116.616.012.7118.45295.30Endometrium000.000.7368.210.00Esophagus000.001.3736.500.00Heart Clontech000.001.3237.880.00Hypothalamus000.000.32155.280.00Ileum015.157.582.5819.38146.80Jejunum40.8616.7928.836.607.58218.37Kidney000.002.1223.580.00Liver012.56.251.5033.33208.33Fetal Liver Clontech293.5393.13343.3210.404.811650.55Lung000.002.5719.460.00Mammary Gland91.08118.14104.6113.003.85402.35ClontechMyometrium026.4313.222.3421.37282.37Omentum000.003.9412.690.00Ovary22.6512.7617.714.3411.52203.97Pancreas000.000.8161.800.00Head of Pancreas000.001.5731.850.00Parotid Gland23.3224.0723.705.489.12216.20Placenta Clontech28.234.7131.465.269.51299.00Prostate000.003.0016.670.00Rectum000.001.2340.650.00Salivary Gland52.4855.9654.227.316.84370.86ClontechSkeletal Muscle000.001.2639.680.00ClontechSkin000.001.2141.320.00Small Intestine000.000.9851.070.00ClontechSpleen13.8306.924.9210.1670.27Stomach000.002.7318.320.00Testis Clontech000.000.5787.870.00Thymus Clontech409.4502.34455.879.895.062304.70Thyroid22.5517.2419.902.7718.05359.12Trachea Clontech73.0252.662.819.715.15323.43Urinary Bladder000.005.479.140.00Uterus024.5412.275.349.36114.89copies ofRegmRNASamplenumberMeandetected/50 ngFold Changesbg655871calgizzarin-(GSKGOItotalin Diseaselikeidentifier)copiesRNASamplePopulationcolon normal GW98-16721941263.68527.36colon normalcolon tumor GW98-16621940566.891133.78colon tumor2.15colon normal GW98-1782208048.8797.74colon normalcolon tumor GW98-17722060188.64377.28colon tumor3.86colon normal GW98-56123514113.25226.50colon normalcolon tumor GW98-56023513196.14392.28colon tumor1.73colon normal GW98-89424691318.81637.62colon normalcolon tumor GW98-89324690460.8921.60colon tumor1.45lung normal GW98-320742508.761017.52lung normallung tumor GW98-220741124.1248.20lung tumor−4.10lung normal GW97-17920677601.781203.56lung normallung tumor GW97-17820676316.85633.70lung tumor−1.90lung normal GW98-16521922913.611827.22lung normallung tumor GW98-16421921747.361494.72lung tumor−1.22lung normal GW98-28222584216.1432.20lung normallung tumor GW98-28122583177.97355.94lung tumor−1.21breast normal GW00-39228750186.88186.88breast normalbreast tumor GW00-39128746278.12556.24breast tumor2.98breast normal GW00-4132879800.00breast normalbreast tumor GW00-41228797804.191608.38breast tumor1608.38breast normal GW00-27592-9500.00breast normal235:238breast tumor GW00-27588-9100.00breast tumor0.00231:234breast normal GW98-62123656716.411432.82breast normalbreast tumor GW98-62023655436.65873.30breast tumor−1.64brain normal BB99-54225507404.96809.92brain normalbrain normal BB99-40625509496.2992.40brain normalbrain normal BB99-9042554690.22180.44brain normalbrain stage 5 ALZ BB99-2550290.86181.72brain stage 5−3.64874ALZbrain stage 5 ALZ BB99-25503379.2758.40brain stage 51.15887ALZbrain stage 5 ALZ BB99-25504278.99557.98brain stage 5−1.18862ALZbrain stage 5 ALZ BB99-25542316.21632.42brain stage 5−1.05927ALZCT lung KCnormal260.58521.16CT lunglung 26 KCnormal00.00lung 26lung 27 KCnormal00.00lung 27lung 24 KCCOPD00.00lung 24−130.29lung 28 KCCOPD00.00lung 28−130.29lung 23 KCCOPD00.00lung 23−130.29lung 25 KCnormal00.00lung 25asthmatic lung ODO31122932100.00asthmatic lung−130.29asthmatic lung ODO34332932325.951.80asthmatic lung−2.52asthmatic lung ODO339729322274.29548.58asthmatic lung4.21asthmatic lung ODO49282932576.05152.10asthmatic lung1.17endo cells KCcontrol00.00endo cellsendo VEGF KC15.5715.57endo VEGF15.57endo bFGF KC24.3624.36endo bFGF24.36heart Clontechnormal00.00heartheart (T-1) ischemic29417286.72573.44heart T-1573.44heart (T-14) non-29422160.22320.44heart T-14320.44obstructive DCMheart (T-3399) DCM29426212.95425.90heart T-3399425.90adenoid GW99-26926162404.24808.48adenoidtonsil GW98-280225821077.532155.06tonsilT cells PC0031428453562.081124.16T cellsPBMNC KC00.00PBMNCmonocyte KC00.00monocyteB cells PC0066528455925.741851.48B cellsdendritic cells 2844156.59113.18dendritic cellsneutrophils2844083.2983.29neutrophilseosinophils28446399.07798.14eosinophilsBM unstim KC00.00BM unstimBM stim KC24.0324.03BM stim24.03osteo dif KC00.00osteo dif0.00osteo undif KC00.00osteo undifchondrocytes59.55148.88chondrocytesOA Synovium IP12/012946217.3117.31OA SynoviumOA Synovium NP10/0129461222.82445.64OA SynoviumOA Synovium NP57/0028464267.63535.26OA SynoviumRA Synovium NP03/0128466227.09454.18RA SynoviumRA Synovium NP71/0028467638.531277.06RA SynoviumRA Synovium NP45/00284751088.592177.18RA SynoviumOA bone (biobank)2921766.4566.45OA bone(biobank)OA bone Sample 1J. Emory205.74411.48OA boneOA bone Sample 2J. Emory679.551359.10OA boneCartilage (pool)Normal736.081472.16Cartilage(pool)Cartilage (pool)OA286.47572.94Cartilage−2.57(pool)PBL unifected284411155.622311.24PBL unifectedPBL HIV IIIB28442763.531527.06PBL HIV IIIB−1.51MRC5 uninfected2915897.19194.38MRC5(100%)uninfected(100%)MRC5 HSV strain F2917830.3860.76MRC5 HSV−3.20strain FW12 cells29179182.95365.90W12 cellsKeratinocytes29180211.73423.46Keratinocytes

[0150] Gene Name sbg655871calgizzarin-like

24Fold Change in DiseasePopulation Relative toDisease tissuesNormalcolon tumor2.15colon tumor3.86colon tumor1.73colon tumor1.45lung tumor−4.10lung tumor−1.90lung tumor−1.22lung tumor−1.21breast tumor2.98breast tumor1608.38breast tumor0.00breast tumor−1.64brain stage 5 ALZ−3.64brain stage 5 ALZ1.15brain stage 5 ALZ−1.18brain stage 5 ALZ−1.05lung 24−130.29lung 28−130.29lung 23−130.29asthmatic lung−130.29asthmatic lung−2.52asthmatic lung4.21asthmatic lung1.17endo VEGF15.57endo bFGF24.36heart T-1573.44heart T-14320.44heart T-3399425.90BM stim24.03osteo dif0.00Cartilage (pool)−2.57PBL HIV IIIB−1.51MRC5 HSV strain F−3.20

[0151] Gene Name sbg506454MPG-1

[0152] Significant upregulation in one breast adenocarcinoma sufficient to make a claim for breast cancer. Widespread expression in immune cell populations, upregulated expression in 3 of 4 asthmatic lungs and high expression in RA and OA synovium, OA bone and cartilage suggest involvement in asthma, OA, and RA disease. Expression in GI tract as well as subcutaneous adipose suggest claims in IBS, IBD, and crohn's diseases. Expression in subcutaneous adipose and omentum (a fat depot) suggests claim for dyslipidemia and obesity.

25copies ofmRNAdetected/Mean GOIMean GOIAverage18S50 ng/18S50 ngSamplecopiescopiesGOIrRNArRNAtotalsbg506454MPG-1(sample 1)(sample 2)Copies(ng)(ng)RNASubcutaneous32.4622.0227.243.0616.34445.10Adipocytes ZenbioSubcutaneous Adipose000.000.9652.360.00ZenbioAdrenal Gland Clontech000.000.6181.970.00Whole Brain Clontech9195.4912359.1110777.307.246.9174428.87Fetal Brain Clontech8.1412.9510.550.48103.951096.15Cerebellum Clontech161.3987.85124.622.1723.042871.43Cervix58.7335.9547.342.4220.66978.10Colon11.7541.6726.712.7118.45492.80Endometrium015.547.770.7368.21530.01Esophagus012.096.051.3736.50220.62Heart Clontech000.001.3237.880.00Hypothalamus010.735.370.32155.28833.07Ileum16.4923.8920.192.5819.38391.28Jejunum82.0838.9460.516.607.58458.41Kidney39.0610.7224.892.1223.58587.03Liver41.2328.7134.971.5033.331165.67Fetal Liver Clontech100.26139.8120.0310.404.81577.07Lung4.202.102.5719.4640.86Mammary Gland75.84122.2699.0513.003.85380.96ClontechMyometrium15.7659.2537.512.3421.37801.39Omentum35.0566.7150.883.9412.69645.69Ovary96.27189.21142.744.3411.521644.47Pancreas4.9802.490.8161.80153.89Head of Pancreas000.001.5731.850.00Parotid Gland13.16107.0360.105.489.12548.31Placenta Clontech000.005.269.510.00Prostate000.003.0016.670.00Rectum27.6815.4421.561.2340.65876.42Salivary Gland31.3147.739.517.316.84270.21ClontechSkeletal Muscle08.624.311.2639.68171.03ClontechSkin23.34.3113.811.2141.32570.45Small Intestine000.000.9851.070.00ClontechSpleen30.6015.304.9210.16155.49Stomach22.7437.7130.232.7318.32553.57Testis Clontech000.000.5787.870.00Thymus Clontech437.25466.27451.769.895.062283.92Thyroid29.7311.5120.622.7718.05372.20Trachea Clontech32.3884.8458.619.715.15301.80Urinary Bladder49.9672.2161.095.479.14558.36Uterus138.38160.37149.385.349.361398.64copies ofRegmRNAFoldnumberMeandetected/50 ngChange inSample(GSKGOItotalDiseasesbg506454MPG-1identifier)copiesRNASamplePopulationcolon normal GW98-167219412762.25524.40colon normalcolon tumor GW98-166219404187.48374.80colon tumor1.52colon normal GW98-17822080304.95609.90colon normalcolon tumor GW98-17722060591.091182.18colon tumor1.94colon normal GW98-561235141334.042668.08colon normalcolon tumor GW98-56023513773.621547.24colon tumor−1.72colon normal GW98-894246915252.8110505.62colon normalcolon tumor GW98-893246901582.613165.22colon tumor−3.32lung normal GW98-3207425609.7111219.42lung normallung tumor GW98-220741244.73489.46lung tumor−22.92lung normal GW97-179206775225.6310451.26lung normallung tumor GW97-178206763397.16794.20lung tumor−1.54lung normal GW98-165219224925.89851.60lung normallung tumor GW98-164219213628.097256.18lung tumor−1.36lung normal GW98-282225841689.763379.52lung normallung tumor GW98-281225832126.384252.76lung tumor1.26breast normal GW00-39228750919.61919.61breast normalbreast tumor GW00-39128746844.851689.70breast tumor1.84breast normal GW00-41328798402.44402.44breast normalbreast tumor GW00-412287974379.698759.38breast tumor21.77breast normal GW00-27592-9559.6159.61breast normal235: 238breast tumor GW00-27588-91182.62182.62breast tumor3.06231: 234breast normal GW98-621236561437.562875.12breast normalbreast tumor GW98-620236551973.413946.82breast tumor1.37brain normal BB99-54225507151.01302.02brain normalbrain normal BB99-40625509220.06440.12brain normalbrain normal BB99-90425546118236.00brain normalbrain stage 5 ALZ BB99-2550237.4474.88brain stage 5−4.35874ALZbrain stage 5 ALZ BB99-25503475.99951.98brain stage 52.92887ALZbrain stage 5 ALZ BB99-25504175.26350.52brain stage 51.08862ALZbrain stage 5 ALZ BB99-25542127.66255.32brain stage 5−1.28927ALZCT lung KCnormal2040.924081.84CT lunglung 26 KCnormal304.9304.90lung 26lung 27 KCnormal97.5197.51lung 27lung 24 KCCOPD179.61179.61lung 24−6.45lung 28 KCCOPD345.33345.33lung 28−3.35lung 23 KCCOPD181.29181.29lung 23−6.39lung 25 KCnormal147.65147.65lung 25asthmatic lung ODO311229321299.26299.26asthmatic lung−3.87asthmatic lung ODO343329323670013400.00asthmatic lung11.57asthmatic lung ODO33972932210865.4321730.86asthmatic lung18.77asthmatic lung ODO4928293255532.7311065.46asthmatic lung9.56endo cells KCcontrol00.00endo cellsendo VEGF KC00.00endo VEGF0.00endo bFGF KC00.00endo bFGF0.00heart Clontechnormal4533.279066.54heartheart (T-1) ischemic29417996.351992.70heart T-1−4.55heart (T-14) non-29422787.371574.74heart T-14−5.76obstructive DCMheart (T-3399) DCM294261496.182992.36heart T-3399−3.03adenoid GW99-269261627988.6915977.38adenoidtonsil GW98-280225829400.618801.20tonsilT cells PC00314284531806.513613.02T cellsPBMNC KC1206.111206.11PBMNCmonocyte KC2460.194920.38monocyteB cells PC006652845524529.3349058.66B cellsdendritic cells 2844157867.91115735.82dendritic cellsneutrophils2844034334.7334334.73neutrophilseosinophils284467309.0514618.10eosinophilsBM unstim KC592.73592.73BM unstimBM stim KC2305.642305.64BM stim3.89osteo dif KC00.00osteo dif0.00osteo undif KC00.00osteo undifchondrocytes3.919.78chondrocytesOA Synovium IP12/01294624075.044075.04OA SynoviumOA Synovium NP10/01294613058.766117.52OA SynoviumOA Synovium NP57/002846410311.7320623.46OA SynoviumRA Synovium NP03/012846615610.6331221.26RA SynoviumRA Synovium NP71/002846716336.7232673.44RA SynoviumRA Synovium NP45/002847525648.151296.20RA SynoviumOA bone (biobank)292172045.312045.31OA bone(biobank)OA bone Sample 1J. Emory8940.8917881.78OA boneOA bone Sample 2J. Emory10348.4520696.90OA boneCartilage (pool)Normal4762.299524.58Cartilage(pool)Cartilage (pool)OA2412.924825.84Cartilage−1.97(pool)PBL unifected284413559.787119.56PBL unifectedPBL HIV IIIB2844210815.5821631.16PBL HIV IIIB3.04MRC5 uninfected2915872.21144.42MRC5(100%)uninfected(100%)MRC5 HSV strain F29178133.55267.10MRC5 HSV1.85strain FW12 cells291796.7413.48W12 cellsKeratinocytes291803.557.10Keratinocytes

[0153] Gene Name sbg506454MPG-1

26Fold Change in DiseasePopulation Relative toDisease tissuesNormalcolon tumor1.52colon tumor1.94colon tumor−1.72colon tumor−3.32lung tumor−22.92lung tumor−1.54lung tumor−1.36lung tumor1.26breast tumor1.84breast tumor21.77breast tumor3.06breast tumor1.37brain stage 5 ALZ−4.35brain stage 5 ALZ2.92brain stage 5 ALZ1.08brain stage 5 ALZ−1.28lung 24−6.45lung 28−3.35lung 23−6.39asthmatic lung−3.87asthmatic lung11.57asthmatic lung18.77asthmatic lung9.56endo VEGF0.00endo bFGF0.00heart T-1−4.55heart T-14−5.76heart T-3399−3.03BM stim3.89osteo dif0.00Cartilage (pool)−1.97PBL HIV IIIB3.04MRC5 HSV strain F1.85

[0154] Gene Name sbg6598370BCAM

[0155] Highest in brain but not changed in alzheimers. Significantly increased expression in one tumor each of colon and lung sufficient to claim colon and lung cancer. Upregulated expression in ischemic and non-obstructive DCM suggesting possible roles in these diseases

27copies ofmRNAdetected/Mean GOIMean GOIAverage18S50 ng/18S50 ngSamplecopiescopiesGOIrRNArRNAtotalsbg659837OBCAM(sample 1)(sample 2)Copies(ng)(ng)RNASubcutaneous1.155.283.223.0616.3452.53Adipocytes ZenbioSubcutaneous Adipose5.255.545.400.9652.36282.46ZenbioAdrenal Gland Clontech00.470.240.6181.9719.26Whole Brain Clontech70048885.247944.627.246.9154866.16Fetal Brain Clontech63.331.8847.590.48103.954946.99Cerebellum Clontech113.8699.7106.782.1723.042460.37Cervix00.90.452.4220.669.30Colon9.4504.732.7118.4587.18Endometrium0.959.525.240.7368.21357.09Esophagus0.930.410.671.3736.5024.45Heart Clontech2.381.461.921.3237.8872.73Hypothalamus15.193.039.110.32155.281414.60Ileum00.170.092.5819.381.65Jejunum8.839.379.106.607.5868.94Kidney1.880.131.012.1223.5823.70Liver0.519.099.801.5033.33326.50Fetal Liver Clontech29.2424.4726.8610.404.81129.11Lung1.590.571.082.5719.4621.01Mammary Gland18.8315.417.1213.003.8565.83ClontechMyometrium1.610.471.042.3421.3722.22Omentum5.140.362.753.9412.6934.90Ovary7.559.88.684.3411.5299.94Pancreas0.1500.080.8161.804.64Head of Pancreas7.7903.901.5731.85124.04Parotid Gland15.8317.0216.435.489.12149.86Placenta Clontech0.1112.026.075.269.5157.65Prostate0.392.261.333.0016.6722.08Rectum2.790.431.611.2340.6565.45Salivary Gland0.484.212.357.316.8416.04ClontechSkeletal Muscle0.400.201.2639.687.94ClontechSkin8.940.494.721.2141.32194.83Small Intestine0.560.680.620.9851.0731.66ClontechSpleen0.179.764.974.9210.1650.46Stomach0.4710.355.412.7318.3299.08Testis Clontech16.852.959.900.5787.87869.95Thymus Clontech9.8719.2714.579.895.0673.66Thyroid000.002.7718.050.00Trachea Clontech2.6121.8812.259.715.1563.05Urinary Bladder0.495.22.855.479.1426.01Uterus15.1410.8412.995.349.36121.63copies ofRegmRNAnumberMeandetected/50 ngFold ChangeSample(GSKGOItotalin Diseasesbg659837OBCAMidentifier)copiesRNASamplePopulationcolon normal GW98-1672194161.2122.40colon normalcolon tumor GW98-16621940220.5441.00colon tumor3.60colon normal GW98-1782208012.3424.68colon normalcolon tumor GW98-1772206011.2122.42colon tumor−1.10colon normal GW98-5612351415.4930.98colon normalcolon tumor GW98-56023513146.12292.24colon tumor9.43colon normal GW98-894246917.2714.54colon normalcolon tumor GW98-8932469020.8341.66colon tumor2.87lung normal GW98-32074212.5525.10lung normallung tumor GW98-22074119.3438.68lung tumor1.54lung normal GW97-17920677934.941869.88lung normallung tumor GW97-178206763.97.80lung tumor−239.73lung normal GW98-165219220.961.92lung normallung tumor GW98-16421921108.12216.24lung tumor112.63lung normal GW98-282225848.2516.50lung normallung tumor GW98-281225836.2112.42lung tumor−1.33breast normal GW00-392287509.439.43breast normalbreast tumor GW00-3912874618.0236.04breast tumor3.82breast normal GW00-4132879813.4213.42breast normalbreast tumor GW00-412287971.943.88breast tumor−3.46breast normal GW00-27592-954.614.61breast normal235: 238breast tumor GW00-27588-9110.1610.16breast tumor2.20231: 234breast normal GW98-6212365618.6537.30breast normalbreast tumor GW98-6202365513.9627.92breast tumor−1.34brain normal BB99-54225507812.471624.94brain normalbrain normal BB99-40625509231.81463.62brain normalbrain normal BB99-90425546583.171166.34brain normalbrain stage 5 ALZ BB99-25502200.73401.46brain stage 5−2.70874ALZbrain stage 5 ALZ BB99-25503685.931371.86brain stage 51.26887ALZbrain stage 5 ALZ BB99-25504585.81171.60brain stage 51.08862ALZbrain stage 5 ALZ BB99-25542329.32658.64brain stage 5−1.65927ALZCT lung KCnormal17.535.00CT lunglung 26 KCnormal8.078.07lung 26lung 27 KCnormal0.30.30lung 27lung 24 KCCOPD0.450.45lung 24−24.09lung 28 KCCOPD0.220.22lung 28−49.28lung 23 KCCOPD00.00lung 23−10.84lung 25 KCnormal00.00lung 25asthmatic lung ODO3112293210.520.52asthmatic lung−20.85asthmatic lung ODO3433293230.71.40asthmatic lung−7.74asthmatic lung ODO3397293221.963.92asthmatic lung−2.77asthmatic lung ODO4928293256.3512.70asthmatic lung1.17endo cells KCcontrol00.00endo cellsendo VEGF KC00.00endo VEGF0.00endo bFGF KC0.90.90endo bFGF0.90heart Clontechnormal00.00heartheart (T-1) ischemic2941712.8925.78heart T-125.78heart (T-14) non-2942212.2724.54heart T-1424.54obstructive DCMheart (T-3399) DCM2942600.00heart T-33990.00adenoid GW99-269261624.889.76adenoidtonsil GW98-280225821.132.26tonsilT cells PC00314284535.9911.98T cellsPBMNC KC00.00PBMNCmonocyte KC0.150.30monocyteB cells PC00665284554.629.24B cellsdendritic cells 284411.332.66dendritic cellsneutrophils284401.861.86neutrophilseosinophils284463.767.52eosinophilsBM unstim KC0.150.15BM unstimBM stim KC0.990.99BM stim6.60osteo dif KC00.00osteo dif0.00osteo undif KC00.00osteo undifchondrocytes6.0915.23chondrocytesOA Synovium IP12/012946229.1629.16OA SynoviumOA Synovium NP10/01294617.6115.22OA SynoviumOA Synovium NP57/002846410.6521.30OA SynoviumRA Synovium NP03/01284660.841.68RA SynoviumRA Synovium NP71/002846710.0120.02RA SynoviumRA Synovium NP45/00284753.777.54RA SynoviumOA bone (biobank)292171.341.34OA bone(biobank)OA bone Sample 1J. Emory13.9627.92OA boneOA bone Sample 2J. Emory5.8211.64OA boneCartilage (pool)Normal8.917.80Cartilage(pool)Cartilage (pool)OA5.8811.76Cartilage−1.51(pool)PBL unifected2844137.2374.46PBL unifectedPBL HIV IIIB2844212.7525.50PBL HIV IIIB−2.92MRC5 uninfected291581.883.76MRC5(100%)uninfected(100%)MRC5 HSV strain F291784.719.42MRC5 HSV2.51strain FW12 cells291792.44.80W12 cellsKeratinocytes291800.470.94Keratinocytes

[0156] Gene Name sbg6598370BCAM

28Fold Change in DiseasePopulation Relative toDisease tissuesNormalcolon tumor3.60colon tumor−1.10colon tumor9.43colon tumor2.87lung tumor1.54lung tumor−239.73lung tumor112.63lung tumor−1.33breast tumor3.82breast tumor−3.46breast tumor2.20breast tumor−1.34brain stage 5 ALZ−2.70brain stage 5 ALZ1.26brain stage 5 ALZ1.08brain stage 5 ALZ−1.65lung 24−24.09lung 28−49.28lung 23−10.84asthmatic lung−20.85asthmatic lung−7.74asthmatic lung−2.77asthmatic lung1.17endo VEGF0.00endo bFGF0.90heart T-125.78heart T-1424.54heart T-33990.00BM stim6.60osteo dif0.00Cartilage (pool)−1.51PBL HIV IIIB−2.92MRC5 HSV strain F2.51

[0157] Gene Name sbg467870CBP

[0158] Expression in fetal liver, thymus, monocytes, adenoid, and tonsil consistent with role in I inflammation. Upregulated in 2 of 4 asthmatic lungs, expression in OA and RA synovium, chondrocyte cells and cartilage, OA bone, and RA synovia suggest involvement in asthma, osteoarthritis, and rheumatoid arthritis. Upregulated in differentiated osteoblasts and expression in OA bone suggests possible involvement in bone disease such as osteoporosis. Down-regulated expression in HSV infected lung cell line suggest possible host factor for HSV infection. Expressed in brain but not changed in alzheimers disease.

29copies ofmRNAdetected/Mean GOIMean GOIAverage18S50 ng/18S50 ngSamplecopiescopiesGOIrRNArRNAtotalsbg467870CBP(sample 1)(sample 2)Copies(ng)(ng)RNASubcutaneous122.51171.63147.073.0616.342403.10Adipocytes ZenbioSubcutaneous Adipose1.4513.477.460.9652.36390.58ZenbioAdrenal Gland Clontech000.000.6181.970.00Whole Brain Clontech3940.124641.934291.037.246.9129634.15Fetal Brain Clontech3.5301.770.48103.95183.47Cerebellum Clontech22.7510.0416.402.1723.04377.76Cervix29.8135.4332.622.4220.66673.97Colon28.2954.0641.182.7118.45759.69Endometrium30.5634.6832.620.7368.212225.10Esophagus17.6820.4919.091.3736.50696.53Heart Clontech28.338.2918.311.3237.88693.56Hypothalamus3.3301.670.32155.28258.54Ileum61.2551.556.382.5819.381092.54Jejunum67.83122.1594.996.607.58719.62Kidney16.1862.8339.512.1223.58931.72Liver18.147.1232.611.5033.331087.00Fetal Liver Clontech2254.061918.752086.4110.404.8110030.79Lung22.1521.1921.672.5719.46421.60Mammary Gland601.21800.88701.0513.003.852696.33ClontechMyometrium111.8792.21102.042.3421.372180.34Omentum127.05139.02133.043.9412.691688.26Ovary101.5683.6692.614.3411.521066.94Pancreas05.972.990.8161.80184.49Head of Pancreas16.973.991.5731.85126.91Parotid Gland73.9699.3186.645.489.12790.47Placenta Clontech418.31231.45324.885.269.513088.21Prostate48.0184.0466.033.0016.671100.42Rectum36.5653.9945.281.2340.651840.45Salivary Gland121.88154.83138.367.316.84946.34ClontechSkeletal Muscle21.46010.731.2639.68425.79ClontechSkin28.3120.6324.471.2141.321011.16Small Intestine11.035.848.440.9851.07430.80ClontechSpleen25.233.2429.224.9210.16296.95Stomach31.1551.941.532.7318.32760.53Testis Clontech06.473.240.5787.87284.27Thymus Clontech2456.562161.412308.999.895.0611673.33Thyroid32.7362.247.472.7718.05856.77Trachea Clontech129.76145.42137.599.715.15708.50Urinary Bladder137.82144.51141.175.479.141290.36Uterus166.73180.21173.475.349.361624.25copies ofRegmRNAnumberdetected/50 ngFold ChangeSample(GSKMean GOItotalin Diseasesbg467870CBPidentifier)copiesRNASamplePopulationcolon normal GW98-167219415005.2110010.42colon normalcolon tumor GW98-1662194015849.631699.20colon tumor3.17colon normal GW98-178220801796.633593.26colon normalcolon tumor GW98-177220602527.095054.18colon tumor1.41colon normal GW98-561235141769.843539.68colon normalcolon tumor GW98-560235134004.288008.56colon tumor2.26colon normal GW98-894246912496.84993.60colon normalcolon tumor GW98-893246905145.9210291.84colon tumor2.06lung normal GW98-3207422177.034354.06lung normallung tumor GW98-2207412751.545503.08lung tumor1.26lung normal GW97-179206775925.1611850.32lung normallung tumor GW97-178206765250.9610501.92lung tumor−1.13lung normal GW98-165219222705.565411.12lung normallung tumor GW98-1642192110468.5420937.08lung tumor3.87lung normal GW98-282225841959.863919.72lung normallung tumor GW98-28122583937.141874.28lung tumor−2.09breast normal GW00-392287504102.064102.06breast normalbreast tumor GW00-391287462805.025610.04breast tumor1.37breast normal GW00-413287984564.074564.07breast normalbreast tumor GW00-412287975045.7210091.44breast tumor2.21breast normal GW00-27592-953527.383527.38breast normal235: 238breast tumor GW00-27588-914475.084475.08breast tumor1.27231: 234breast normal GW98-621236565436.3810872.76breast normalbreast tumor GW98-620236557555.6515111.30breast tumor1.39brain normal BB99-542255074185.898371.78brain normalbrain normal BB99-406255091474.432948.86brain normalbrain normal BB99-90425546824.951649.90brain normalbrain stage 5 ALZ BB99-25502439.29878.58brain stage 5−4.92874ALZbrain stage 5 ALZ BB99-255031034.442068.88brain stage 5−2.09887ALZbrain stage 5 ALZ BB99-255042189.424378.84brain stage 51.01862ALZbrain stage 5 ALZ BB99-255422009.164018.32brain stage 5−1.08927ALZCT lung KCnormal2111.764223.52CT lunglung 26 KCnormal308.92308.92lung 26lung 27 KCnormal11.7711.77lung 27lung 24 KCCOPD23.0523.05lung 24−49.55lung 28 KCCOPD217.04217.04lung 28−5.26lung 23 KCCOPD66.6266.62lung 23−17.15lung 25 KCnormal24.6624.66lung 25asthmatic lung ODO3112293213982.983982.98asthmatic3.49lungasthmatic lung ODO3433293232535.375070.74asthmatic4.44lungasthmatic lung ODO33972932210395.5520791.10asthmatic18.20lungasthmatic lung ODO4928293255044.2110088.42asthmatic8.83lungendo cells KCcontrol724.08724.08endo cellsendo VEGF KC607.05607.05endo VEGF−1.19endo bFGF KC346.88346.88endo bFGF−2.09heart Clontechnormal338.3676.60heartheart (T-1) ischemic294177198.6214397.24heart T-121.28heart (T-14) non-294221634.963269.92heart T-144.83obstructive DCMheart (T-3399) DCM294268987.2217974.44heart T-339926.57adenoid GW99-269261621327.732655.46adenoidtonsil GW98-280225823389.076778.14tonsilT cells PC00314284532349.934699.86T cellsPBMNC KC41.0341.03PBMNCmonocyte KC21.3242.64monocyteB cells PC00665284551181.612363.22B cellsdendritic cells 284417521.9315043.86dendritic cellsneutrophils28440248.9248.90neutrophilseosinophils28446874.141748.28eosinophilsBM unstim KC142.11142.11BM unstimBM stim KC635.4635.40BM stim4.47osteo dif KC2464.772464.77osteo dif5.45osteo undif KC452.56452.56osteo undifchondrocytes24737.5661843.90chondrocytesOA Synovium IP12/01294621788.871788.87OASynoviumOA Synovium NP10/01294617842.7915685.58OASynoviumOA Synovium NP57/002846411577.9123155.82OASynoviumRA Synovium NP03/012846619643.9839287.96RA SynoviumRA Synovium NP71/002846722772.8645545.72RA SynoviumRA Synovium NP45/002847516068.3132136.62RA SynoviumOA bone (biobank)292171829.841829.84OA bone(biobank)OA bone Sample 1J. Emory11770.2623540.52OA boneOA bone Sample 2J. Emory2525.125050.24OA boneCartilage (pool)Normal18001.3636002.72Cartilage(pool)Cartilage (pool)OA7463.9514927.90Cartilage−2.41(pool)PBL unifected284413136.916273.82PBLunifectedPBL HIV IIIB284422830.855661.70PBL HIV−1.11IIIBMRC5 uninfected2915825933.2551866.50MRC5(100%)uninfected(100%)MRC5 HSV strain F29178279.28558.56MRC5 HSV−92.86strain FW12 cells291796771.8713543.74W12 cellsKeratinocytes2918022577.245154.40Keratinocytes

[0159] Gene Name sbg467870CBP

30Fold Change in DiseasePopulation Relative toDisease tissuesNormalcolon tumor3.17colon tumor1.41colon tumor2.26colon tumor2.06lung tumor1.26lung tumor−1.13lung tumor3.87lung tumor−2.09breast tumor1.37breast tumor2.21breast tumor1.27breast tumor1.39brain stage 5 ALZ−4.92brain stage 5 ALZ−2.09brain stage 5 ALZ1.01brain stage 5 ALZ−1.08lung 24−49.55lung 28−5.26lung 23−17.15asthmatic lung3.49asthmatic lung4.44asthmatic lung18.20asthmatic lung8.83endo VEGF−1.19endo bFGF−2.09heart T-121.28heart T-144.83heart T-339926.57BM stim4.47osteo dif5.45Cartilage (pool)−2.41PBL HIV IIIB−1.11MRC5 HSV strain F−92.86

[0160] Gene Name sbg514112RNase

[0161] Low expression overall. Upregulated in 4 of 4 colon adenocarcinomas, 2 of 4 lung carcinomas, and 2 of 4 breast carcinomas suggesting claim for all cancers. Expression in spleen, PHA stimulated T and B cells, dendritic cells corroborates expression RA and OA synovium suggesting involvement in RA and OA diseases. Upregulated expression in 2 of 4 asthmatic lungs suggesting role in asthma. Upregulated in ischemic heart suggests possible involvement in ischemic heart disease. Strongly upregulated expression in HSV infected cell line.

31copies ofmRNAdetected/Mean GOIMean GOIAverage18S50 ng/18S50 ngSamplecopiescopiesGOIrRNArRNAtotalsbg514112RNase(sample 1)(sample 2)Copies(ng)(ng)RNASubcutaneous2.2232.613.0616.3442.65Adipocytes ZenbioSubcutaneous Adipose000.000.9652.360.00ZenbioAdrenal Gland Clontech2.311.852.080.6181.97170.49Whole Brain Clontech53.9574.4564.207.246.91443.37Fetal Brain Clontech01.40.700.48103.9572.77Cerebellum Clontech0.71.991.352.1723.0430.99Cervix10.358.549.452.4220.66195.14Colon2.090.841.472.7118.4527.03Endometrium3.82.543.170.7368.21216.23Esophagus3.193.423.311.3736.50120.62Heart Clontech5.211.043.131.3237.88118.37Hypothalamus0.950.960.960.32155.28148.29Ileum2.041.51.772.5819.3834.30Jejunum10.272.156.216.607.5847.05Kidney2.891.112.002.1223.5847.17Liver20.919.2220.061.5033.33668.67Fetal Liver Clontech1.3818.459.9210.404.8147.67Lung2.861.111.992.5719.4638.62Mammary Gland1.191.721.4613.003.855.60ClontechMyometrium1.481.951.722.3421.3736.65Omentum13.350.727.043.9412.6989.28Ovary10.8817.3514.124.3411.52162.62Pancreas0.661.290.980.8161.8060.26Head of Pancreas1.317.174.241.5731.85135.03Parotid Gland2.1901.105.489.129.99Placenta Clontech0.6816.078.385.269.5179.61Prostate1.10.951.033.0016.6717.08Rectum1.844.042.941.2340.65119.51Salivary Gland1.520.911.227.316.848.31ClontechSkeletal Muscle1.790.911.351.2639.6853.57ClontechSkin1.190.861.031.2141.3242.36Small Intestine3.141.722.430.9851.07124.11ClontechSpleen0.934.9517.934.9210.16182.16Stomach0.722.211.472.7318.3226.83Testis Clontech0.691.821.260.5787.87110.28Thymus Clontech1.6617.779.729.895.0649.12Thyroid0.711.471.092.7718.0519.68Trachea Clontech18.7519.0518.909.715.1597.32Urinary Bladder29.841.9615.905.479.14145.34Uterus10.0646.8628.465.349.36266.48copies ofRegmRNAFoldnumberMeandetected/50 ngChange inSample(GSKGOItotalDiseasesbg514112RNaseidentifier)copiesRNASamplePopulationcolon normal GW98-167219416.6113.22colon normalcolon tumor GW98-16621940102.54205.08colon tumor15.51colon normal GW98-178220800.470.94colon normalcolon tumor GW98-1772206013.5727.14colon tumor28.87colon normal GW98-561235144.519.02colon normalcolon tumor GW98-5602351325.1350.26colon tumor5.57colon normal GW98-894246910.551.10colon normalcolon tumor GW98-8932469023.3646.72colon tumor42.47lung normal GW98-3207429.5919.18lung normallung tumor GW98-22074148.1896.36lung tumor5.02lung normal GW97-17920677121.59243.18lung normallung tumor GW97-178206761.082.16lung tumor−112.58lung normal GW98-165219221.73.40lung normallung tumor GW98-1642192125.4550.90lung tumor14.97lung normal GW98-2822258462.77125.54lung normallung tumor GW98-281225830.310.62lung tumor−202.48breast normal GW00-3922875020.5920.59breast normalbreast tumor GW00-3912874613.9327.86breast tumor1.35breast normal GW00-413287986.646.64breast normalbreast tumor GW00-4122879721.9943.98breast tumor6.62breast normal GW00-27592-954.324.32breast normal235: 238breast tumor GW00-27588-9131.5931.59breast tumor7.31231: 234breast normal GW98-6212365624.0548.10breast normalbreast tumor GW98-6202365557.33114.66breast tumor2.38brain normal BB99-5422550734.4968.98brain normalbrain normal BB99-4062550915.3430.68brain normalbrain normal BB99-9042554612.4424.88brain normalbrain stage 5 ALZ BB99-2550222.5645.12brain stage 51.09874ALZbrain stage 5 ALZ BB99-2550339.1678.32brain stage 51.89887ALZbrain stage 5 ALZ BB99-255047.7915.58brain stage 5−2.66862ALZbrain stage 5 ALZ BB99-2554217.3134.62brain stage 5−1.20927ALZCT lung KCnormal0.541.08CT lunglung 26 KCnormal6.446.44lung 26lung 27 KCnormal2.292.29lung 27lung 24 KCCOPD2.852.85lung 241.12lung 28 KCCOPD2.332.33lung 28−1.09lung 23 KCCOPD1.041.04lung 23−2.44lung 25 KCnormal0.330.33lung 25asthmatic lung ODO3112293213.373.37asthmatic lung1.33asthmatic lung ODO3433293232.75.40asthmatic lung2.13asthmatic lung ODO3397293225.7511.50asthmatic lung4.54asthmatic lung ODO49282932511.1622.32asthmatic lung8.80endo cells KCcontrol26.2626.26endo cellsendo VEGF KC50.2150.21endo VEGF1.91endo bFGF KC11.9811.98endo bFGF−2.19heart Clontechnormal3.657.30heartheart (T-1) ischemic2941737.5875.16heart T-110.30heart (T-14) non-294227.8515.70heart T-142.15obstructive DCMheart (T-3399) DCM2942625.0150.02heart T-33996.85adenoid GW99-269261626.3512.70adenoidtonsil GW98-2802258229.1258.24tonsilT cells PC003142845328.1356.26T cellsPBMNC KC0.680.68PBMNCmonocyte KC0.480.96monocyteB cells PC006652845568.51137.02B cellsdendritic cells 2844159118.00dendritic cellsneutrophils284400.50.50neutrophilseosinophils2844600.00eosinophilsBM unstim KC3.413.41BM unstimBM stim KC0.370.37BM stim−9.22osteo dif KC00.00osteo dif0.00osteo undif KC00.00osteo undifchondrocytes0.511.28chondrocytesOA Synovium IP12/01294629.819.81OA SynoviumOA Synovium NP10/01294610.851.70OA SynoviumOA Synovium NP57/002846430.260.40OA SynoviumRA Synovium NP03/01284668.1516.30RA SynoviumRA Synovium NP71/002846734.6869.36RA SynoviumRA Synovium NP45/002847549.6999.38RA SynoviumOA bone (biobank)292170.630.63OA bone(biobank)OA bone Sample 1J. Emory23.5447.08OA boneOA bone Sample 2J. Emory37.1974.38OA boneCartilage (pool)Normal20.0240.04Cartilage (pool)Cartilage (pool)OA6.6613.32Cartilage (pool)−3.01PBL unifected2844121.9543.90PBL unifectedPBL HIV IIIB28442714.00PBL HIV IIIB−3.14MRC5 uninfected2915800.00MRC5(100%)uninfected(100%)MRC5 HSV strain F29178501.821003.64MRC5 HSV1003.64strain FW12 cells291793.767.52W12 cellsKeratinocytes291800.280.56Keratinocytes

[0162] Gene Name sbg514112RNase

32Fold Change in DiseasePopulation Relative toDisease tissuesNormalcolon tumor15.51colon tumor28.87colon tumor5.57colon tumor42.47lung tumor5.02lung tumor−112.58lung tumor14.97lung tumor−202.48breast tumor1.35breast tumor6.62breast tumor7.31breast tumor2.38brain stage 5 ALZ1.09brain stage 5 ALZ1.89brain stage 5 ALZ−2.66brain stage 5 ALZ−1.20lung 241.12lung 28−1.09lung 23−2.44asthmatic lung1.33asthmatic lung2.13asthmatic lung4.54asthmatic lung8.80endo VEGF1.91endo bFGF−2.19heart T-110.30heart T-142.15heart T-33996.85BM stim−9.22osteo undif0.00Cartilage (pool)−3.01PBL HIV IIIB−3.14MRC5 HSV strain F1003.64

[0163] Gene Name sbg962274FGF-BP

[0164] Expressed in brain with highest expression in fetal tissues. Significant expression in hypothalamus and thyroid suggests claims in thyroid disease and and metabolic disease claims related to diabetes, impaired glucose tolerance, metabolic syndrome, and obesity. Upregulated expression in all three heart diseases suggests involvement in non-obstructive DCM, DCM, and ischemic heart disease. Overexpression in one of four breast tumors suggests claim for breast cancer (caveat: undetectable expression in normal adjacent may lead to exaggerated fold overexpression). Immune cell expression in T and B cells, dendritic cells, chondrocytes and stimulated bone marrow consistent with expression in RA and OA synovium, OA bone, and cartilage and suggests involvement in OA and RA diseases.

33copies ofmRNAMean GOIMean GOIAverage18S50 ng/18Sdetected/SamplecopiescopiesGOIrRNArRNA50 ngsbg962274FGF-BP(sample 1)(sample 2)Copies(ng)(ng)total RNASubcutaneous000.003.0616.340.00Adipocytes ZenbioSubcutaneous Adipose000.000.9652.360.00ZenbioAdrenal Gland Clontech000.000.6181.970.00Whole Brain Clontech455.56624.29539.937.246.913728.76Fetal Brain Clontech164.47320.73242.600.48103.9525218.30Cerebellum Clontech99.48123.78111.632.1723.042572.12Cervix63.3461.4662.402.4220.661289.26Colon110.4055.202.7118.451018.45Endometrium000.000.7368.210.00Esophagus000.001.3736.500.00Heart Clontech000.001.3237.880.00Hypothalamus058.7229.360.32155.284559.01Ileum69.65034.832.5819.38674.90Jejunum59.87029.946.607.58226.78Kidney000.002.1223.580.00Liver000.001.5033.330.00Fetal Liver Clontech562.37739.81651.0910.404.813130.24Lung078.5939.302.5719.46764.49Mammary Gland237.04320.2278.6213.003.851071.62ClontechMyometrium91.84179.02135.432.3421.372893.80Omentum159.45158.28158.873.9412.692016.05Ovary70.3035.154.3411.52404.95Pancreas000.000.8161.800.00Head of Pancreas000.001.5731.850.00Parotid Gland230.22319.65274.945.489.122508.53Placenta Clontech103.93101.53102.735.269.51976.52Prostate88.3990.0689.233.0016.671487.08Rectum070.5635.281.2340.651434.15Salivary Gland218.67151.81185.247.316.841267.03ClontechSkeletal Muscle000.001.2639.680.00ClontechSkin000.001.2141.320.00Small Intestine000.000.9851.070.00ClontechSpleen000.004.9210.160.00Stomach000.002.7318.320.00Testis Clontech000.000.5787.870.00Thymus Clontech493.89500.57497.239.895.062513.80Thyroid237.11201.59219.352.7718.053959.39Trachea Clontech124.53114.49119.519.715.15615.40Urinary Bladder72.1492.6182.385.479.14752.97Uterus0115.8657.935.349.36542.42copies ofRegmRNAFoldnumberMeandetected/Change inSample(GSKGOI50 ngDiseasesbg962274FGF-BPidentifier)copiestotal RNASamplePopulationcolon normal GW98-16721941532.511065.02colon normalcolon tumor GW98-16621940597.141194.28colon tumor1.12colon normal GW98-17822080108.63217.26colon normalcolon tumor GW98-17722060433.99867.98colon tumor4.00colon normal GW98-56123514346.17692.34colon normalcolon tumor GW98-56023513485.16970.32colon tumor1.40colon normal GW98-89424691318.86637.72colon normalcolon tumor GW98-89324690711.681423.36colon tumor2.23lung normal GW98-320742447.66895.32lung normallung tumor GW98-220741376.57753.14lung tumor−1.19lung normal GW97-179206771066.582133.16lung normallung tumor GW97-17820676426.93853.86lung tumor−2.50lung normal GW98-16521922947.521895.04lung normallung tumor GW98-16421921539.951079.90lung tumor−1.75lung normal GW98-28222584358.48716.96lung normallung tumor GW98-28122583494.08988.16lung tumor1.38breast normal GW00-39228750293.27293.27breast normalbreast tumor GW00-39128746556.691113.38breast tumor3.80breast normal GW00-4132879800.00breast normalbreast tumor GW00-41228797493.54987.08breast tumor987.08breast normal GW00-27592-9500.00breast normal235:238breast tumor GW00-27588-9100.00breast tumor0.00231:234breast normal GW98-62123656646.31292.60breast normalbreast tumor GW98-62023655519.351038.70breast tumor−1.24brain normal BB99-542255072558.995117.98brain normalbrain normal BB99-406255091640.033280.06brain normalbrain normal BB99-904255461519.523039.04brain normalbrain stage 5 ALZ BB99-25502696.081392.16brain stage 5−2.74874ALZbrain stage 5 ALZ BB99-255031796.623593.24brain stage 5−1.06887ALZbrain stage 5 ALZ BB99-255041654.653309.30brain stage 5−1.15862ALZbrain stage 5 ALZ BB99-25542651.311302.62brain stage 5−2.93927ALZCT lung KCnormal280.34560.68CT lunglung 26 KCnormal00.00lung 26lung 27 KCnormal00.00lung 27lung 24 KCCOPD00.00lung 24−156.37lung 28 KCCOPD00.00lung 28−156.37lung 23 KCCOPD131.98131.98lung 23−1.18lung 25 KCnormal64.8164.81lung 25asthmatic lung ODO31122932135.7735.77asthmatic lung−4.37asthmatic lung ODO343329323323.27646.54asthmatic lung4.13asthmatic lung ODO339729322614.81229.60asthmatic lung7.86asthmatic lung ODO492829325337.93675.86asthmatic lung4.32endo cells KCcontrol00.00endo cellsendo VEGF KC00.00endo VEGF0.00endo bFGF KC00.00endo bFGF0.00heart Clontechnormal103.42206.84heartheart (T-1) ischemic29417326.36652.72heart T-13.16heart (T-14) non-29422799.111598.22heart T-147.73obstructive DCMheart (T-3399) DCM29426885.71771.40heart T-33998.56adenoid GW99-269261621005.582011.16adenoidtonsil GW98-28022582979.881959.76tonsilT cells PC00314284531516.143032.28T cellsPBMNC KC179.43179.43PBMNCmonocyte KC338.32676.64monocyteB cells PC0066528455550.971101.94B cellsdendritic cells 28441619.321238.64dendritic cellsneutrophils28440104.25104.25neutrophilseosinophils2844663.57127.14eosinophilsBM unstim KC00.00BM unstimBM stim KC981.8981.80BM stim981.80osteo dif KC275.28275.28osteo dif1.47osteo undif KC187.39187.39osteo undifchondrocytes1165.742914.35chondrocytesOA Synovium IP12/0129462277.86277.86OA SynoviumOA Synovium NP10/0129461523.261046.52OA SynoviumOA Synovium NP57/0028464445.78891.56OA SynoviumRA Synovium NP03/0128466604.661209.32RA SynoviumRA Synovium NP71/0028467567.561135.12RA SynoviumRA Synovium NP45/0028475466.75933.50RA SynoviumOA bone (biobank)2921772.6772.67OA bone(biobank)OA bone Sample 1J. Emory321.31642.62OA boneOA bone Sample 2J. Emory817.431634.86OA boneCartilage (pool)Normal1280.042560.08Cartilage (pool)Cartilage (pool)OA876.261752.52Cartilage (pool)−1.46PBL unifected284411589.593179.18PBL unifectedPBL HIV IIIB284421286.532573.06PBL HIV IIIB−1.24MRC5 uninfected29158578.81157.60MRC5(100%)uninfected(100%)MRC5 HSV strain F29178184.2368.40MRC5 HSV−3.14strain FW12 cells29179383.66767.32W12 cellsKeratinocytes29180326.35652.70Keratinocytes

[0165] Gene Name sbg962274FGF-BP

34Fold Change in DiseasePopulation Relative toDisease tissuesNormalcolon tumor1.12colon tumor4.00colon tumor1.40colon tumor2.23lung tumor−1.19lung tumor−2.50lung tumor−1.75lung tumor1.38breast tumor3.80breast tumor987.08breast tumor0.00breast tumor−1.24brain stage 5 ALZ−2.74brain stage 5 ALZ−1.06brain stage 5 ALZ−1.15brain stage 5 ALZ−2.93lung 24−156.37lung 28−156.37lung 23−1.18asthmatic lung−4.37asthmatic lung4.13asthmatic lung7.86asthmatic lung4.32endo VEGF0.00endo bFGF0.00heart T-13.16heart T-147.73heart T-33998.56BM stim981.80osteo dif1.47Cartilage (pool)−1.46PBL HIV IIIB−1.24MRC5 HSV strain F−3.14

[0166]

35

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 encephalopathy, 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,

muscle
periodic paralyses, malignant hyperthermia,

paramyotonia congenita, myotonia congenita

Intestine
Gastrointestinal diseases, including Myotonia congenita,

Ileus, Intestinal Obstruction, Tropical Sprue,

Pseudomembranous Enterocolitis

Spleen/
Lymphangiectasia, hypersplenism, angiomas, ankylosing

lymph
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

[0167]

Novel compounds

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