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Detecting Functional Modules of Transcription Factor Binding Sites in the Human Genome

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Regulatory Genomics (RRG 2004)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 3318))

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Abstract

This paper presents a method for predicting biologically meaningful modules of transcription factors. For this purpose, we employ the CORG database of conserved transcription factor binding sites. We aim at enhancing the power of in-silico binding site predictions by employing three crucial constraints. First, we rely on conserved promoter regions of orthologous genes in human and mouse, second we look for synergistic transcription factor modules which bind upstream regions preferentially together, and finally we restrict our results to those modules, whose genes have a significant functional overlap. Many of our predicted binding sites coincide with known biological facts as is evidenced by a direct comparison with a single large-scale experiment for E2F binding. We also identified known combinations of transcription factors with a functional enrichment in the set of their shared target genes. Several new modules are suggested for experimental investigation. Finally we study the transcription factor network and suggest a classification of transcription factors according to their regulatory power and control.

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References

  1. Tavazoie, S., Hughes, J.D., Campbell, M.J., Cho, R.J., Church, G.M.: Systematic determination of genetic network architecture. Nat. Genet. 22, 281–285 (1999)

    Article  Google Scholar 

  2. Duret, L., Bucher, P.: Searching for regulatory elements in human noncoding sequences. Curr. Opin. Struct. Biol. 7, 399–406 (1997)

    Article  Google Scholar 

  3. Dieterich, C., Cusack, B., Wang, H., Rateitschak, K., Krause, A., Vingron, M.: Annotating regulatory DNA based on man-mouse genomic comparison. Bioinformatics 18(Suppl. 2), S84–S90 (2002)

    Google Scholar 

  4. Ren, B., Cam, H., Takahashi, Y., Volkert, T., Terragni, J., Young, R.A., Dynlacht, B.D.: E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints. Genes. Dev. 16, 245–256 (2002)

    Article  Google Scholar 

  5. Levine, M., Tjian, R.: Transcription regulation and animal diversity. Nature 424, 147–151 (2003)

    Article  Google Scholar 

  6. Matys, V., Fricke, E., Geffers, R., Gossling, E., Haubrock, M., Hehl, R., Hornischer, K., Karas, D., Kel, A.E., Kel-Margoulis, O.V., Kloos, D.U., Land, S., Lewicki-Potapov, B., Michael, H., Munch, R., Reuter, I., Rotert, S., Saxel, H., Scheer, M., Thiele, S., Wingender, E.: Transfac: transcriptional regulation, from patterns to profiles. Nucleic Acids Res. 31, 374–378 (2003)

    Article  Google Scholar 

  7. Elkon, R., Linhart, C., Sharan, R., Shamir, R., Shiloh, Y.: Genome-wide in silico identification of transcriptional regulators controlling the cell cycle in human cells. Genome Res. 13, 773–780 (2003)

    Article  Google Scholar 

  8. Alon, U., Barkai, N., Notterman, D.A., Gish, K., Ybarra, S., Mack, D., Levine, A.J.: Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays. Proc. Natl. Acad. Sci. USA 96, 6745–6750 (1999)

    Article  Google Scholar 

  9. Cheng, Y., Church, G.M.: Biclustering of expression data. In: Proc. Int. Conf. Intell. Syst. Mol. Biol., vol. 8, pp. 93–103 (2000)

    Google Scholar 

  10. Sheng, Q., Moreau, Y., Moor, B.D.: Biclustering microarray data by Gibbs sampling. Bioinformatics 19(Suppl. 2), II196–II205 (2003)

    Article  Google Scholar 

  11. Kluger, Y., Basri, R., Chang, J.T., Gerstein, M.: Spectral biclustering of microarray data: coclustering genes and conditions. Genome Res. 13, 703–716 (2003)

    Article  Google Scholar 

  12. Tanay, A., Sharan, R., Shamir, R.: Discovering statistically significant biclusters in gene expression data. Bioinformatics 18(Suppl.1), S136–S144 (2002)

    Google Scholar 

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© 2005 Springer-Verlag Berlin Heidelberg

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Manke, T., Dieterich, C., Vingron, M. (2005). Detecting Functional Modules of Transcription Factor Binding Sites in the Human Genome. In: Eskin, E., Workman, C. (eds) Regulatory Genomics. RRG 2004. Lecture Notes in Computer Science(), vol 3318. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-32280-1_2

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  • DOI: https://doi.org/10.1007/978-3-540-32280-1_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-24456-1

  • Online ISBN: 978-3-540-32280-1

  • eBook Packages: Computer ScienceComputer Science (R0)

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