Claims
- 1. A method for statistical analysis of differentially expressed genes, comprising:
(a) obtaining a set of differentially expressed genes; (b) screening genomic sequences including the regulatory regions of said differentially expressed genes for the presence of regulatory factor binding sites; and (c) identifying at least one regulatory factor binding site enriched within said set of differentially expressed genes relative to a genome-wide or tissue-wide background.
- 2. The method of claim 1 wherein in step (c) enrichment is determined by comparing the frequency or probability of the occurrence of the regulatory binding site or binding sites identified in step (c) within said gene set with the frequency or probability of their occurrence in a genome-wide or tissue-wide background.
- 3. The method of claim 1 wherein prior to obtaining said set of differentially expressed genes, a proteomic profile of a set of differentially expressed proteins is obtained.
- 4. The method of claim 1 wherein said set of differentially expressed genes is part of a gene expression profile characteristic of a disease, disorder, or biological process.
- 5. The method of claim 4 wherein said disease is selected from the group consisting of tumor, oncological diseases, neurological diseases, cardiovascular diseases, renal diseases, infectious diseases, digestive diseases, metabolic diseases, inflammatory diseases, autoimmune diseases, dermatological diseases, and diseases associated with trauma or abnormal skeletal development.
- 6. The method of claim 5 wherein said tumor is cancer.
- 7. The method of claim 6 wherein said cancer is selected from the group consisting of breast cancer, colon cancer, lung cancer, prostate cancer, hepatocellular cancer, gastric cancer, pancreatic cancer, cervical cancer, ovarian cancer, liver cancer, bladder cancer, cancer of the urinary tract, thyroid cancer, renal cancer, carcinoma, melanoma, and brain cancer.
- 8. The method of claim 4 wherein said disorder is a developmental disorder.
- 9. The method of claim 4 wherein said biological process is associated with aging.
- 10. The method of claim 1 wherein said set consists of genes that show at least about two-fold differential expression relative to control.
- 11. The method of claim 1 wherein said set consists of genes that show at least about four-fold differential expression relative to control.
- 12. The method of claim 1 wherein said set consists of genes that show at least about ten-fold differential expression relative to control
- 13. The method of claim 1 wherein said regulatory factor binding site is identified within a region selected from the group consisting of a 5′ upstream core promoter region, a 5′ upstream enhancer region, an intron region, and a 3′ regulatory region.
- 14. The method of claim 13 wherein said regulatory factor binding site is a transcription factor binding site.
- 15. The method of claim 14 wherein said transcription factor is selected from the group consisting of c-Fos, c-Jun, AP-1, Elk, ATF, c-Ets-1, c-Rel, CRF, CTF, GATA-1, POU1F1, NF-κB, POU2F1, POU2F2, p53, Pax-3, Sp1, TCF, TAR, TFEB, TCF-1, TFIIF, E2F-1, E2F-2, E2F-3, E2F-4, HIF-1, HIF-1α, HOXA1, HOXA5, Sp3, Sp4, TCF-4, APC, and STAT5A.
- 16. The method of claim 15 wherein said transcription factor is selected from the group consisting of E2F-1, E2F-2, E2F-3, NF-κB, Elk, AP-1, c-Fos, and c-Jun.
- 17. The method of claim 1 wherein at least 50 differentially expressed genes are analyzed.
- 18. The method of claim 1 wherein at least 100 differentially expressed genes are analyzed.
- 19. The method of claim 1 wherein at least 500 differentially expressed genes are analyzed.
- 20. The method of claim 1 further comprising the step of designing a treatment strategy based upon the identification of said enriched regulatory factor binding site.
- 21. The method of claim 20 wherein said enriched regulatory factor binding site is a transcription factor binding site binding to at least one transcription factor.
- 22. The method of claim 21 wherein a consensus binding site is identified based on said enriched transcription factor binding site.
- 23. The method of claim 20 wherein said treatment strategy relies on the design of a double-stranded oligonucleotide decoy, which competes with said enriched binding site for binding to the corresponding transcription factor.
- 24. The method of claim 20 wherein said treatment strategy relies on an anti-sense oligonucleotide designed to bind to said enriched binding site.
- 25. A method of designing a consensus regulatory factor binding site, comprising identifying a regulatory factor binding site enriched within a set of differentially expressed genes, relative to a genome-wide or tissue-wide control, and designing a consensus regulatory factor binding site consisting essentially of nucleotides shared by the regulatory factor binding sites enriched within said set of differentially expressed genes.
- 26. A method of analyzing the enrichment of a regulatory factor binding site in a biological sample comprising a set of differentially expressed genes, comprising comparing the frequency or probability of the occurrence of said regulatory binding site within said gene set with the frequency or probability of its occurrence in a reference sample.
- 27. The method of claim 26 wherein the biological sample is a tissue sample.
- 28. The method of claim 27 wherein the tissue comprises tumor cells.
- 29. The method of claim 28 wherein the tissue comprises cancer cells.
- 30. The method of claim 28 wherein the cancer is selected from the group consisting of breast cancer, colon cancer, lung cancer, prostate cancer, hepatocellular cancer, gastric cancer, pancreatic cancer, cervical cancer, ovarian cancer, liver cancer, bladder cancer, cancer of the urinary tract, thyroid cancer, renal cancer, carcinoma, melanoma, and brain cancer.
- 31. The method of claim 28 wherein the reference sample is a normal tissue of the same tissue type.
- 32. The method of claim 28 wherein the reference sample is the human genome.
- 33. The method of claim 26 wherein the biological sample is a biological fluid.
- 34. The method of claim 26 wherein the enrichment is determined by using hypergeometric distribution analysis.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is related to U.S. Ser. No. ______, filed ______, entitled “Genomic Profiling of Regulatory Factor Binding Sites”, and identified as Attorney Docket No. 39753-0001, the entire disclosure of which is hereby expressly incorporated by reference.