Abstract
An important topic in computational biology is to identify transcriptional modules through sequence analysis and gene expression profiling. A transcriptional module is formed by a group of genes under control of one or several transcription factors (TFs) that bind to cis-regulatory elements in the promoter regions of those genes. In this paper, we develop an integrative approach, namely motif-guided sparse decomposition (mSD), to uncover transcriptional modules by combining motif information and gene expression data. The method exploits the interplay of co-expression and co-regulation to find regulated gene patterns guided by TF binding information. Specifically, a motif-guided clustering method is first developed to estimate transcription factor binding activities (TFBAs); sparse component analysis is then followed to further identify TFs’ target genes. The experimental results show that the mSD approach can successfully help uncover condition-specific transcriptional modules that may have important implications in endocrine therapy of breast cancer.
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References
Speed, T.: Statistical Analysis of Gene Expression Microarray Data. Chapman & Hall/CRC (2003)
Nguyen, D.H., D’Haeseleer, P.: Deciphering principles of transcription regulation in eukaryotic genomes. Mol. Syst. Biol. 2 (2006)
Roth, F.P., et al.: Finding DNA regulatory motifs within unaligned noncoding sequences clustered by whole-genome mRNA quantitation. Nat Biotech 16(10), 939–945 (1998)
Jin, V.X., et al.: A computational genomics approach to identify cis-regulatory modules from chromatin immunoprecipitation microarray data–A case study using E2F1. Genome Res. 16(12), 1585–1595 (2006)
Smith, A.D., et al.: Mining ChIP-chip data for transcription factor and cofactor binding sites. Bioinformatics 21(suppl. 1), 403–412 (2005)
Liao, J.C., et al.: Network component analysis: Reconstruction of regulatory signals in biological systems. Proceedings of the National Academy of Sciences 100(26), 15522–15527 (2003)
Georgiev, P., Theis, F., Cichocki, A.: Sparse component analysis and blind source separation of underdetermined mixtures. Neural Networks, IEEE Transactions 16(4), 992–996 (2005)
Schacherer, F., et al.: TRANSFAC: an integrated system for gene expression regulation. Nucleic Acids Research 28, 316–319 (2000)
Hartigan, J.A., Wong, M.A.: A K-means clustering algorithm. App. Statist. 28, 100–108 (1978)
Kohonen, T.: Self-Organizing Maps. Springer, NY (1997)
Frey, B.J., Dueck, D.: Clustering by Passing Messages Between Data Points. Science 315(5814), 972–976 (2007)
Arash Ali, A., Massoud, B.-Z., Christian, J.: A Fast Method for Sparse Component Analysis Based on Iterative Detection-Estimation. In: AIP Conference Proceedings, vol. 872(1), pp. 123–130 (2006)
Lin, C.-Y., et al.: Discovery of estrogen receptor alpha target genes and response elements in breast tumor cells. Genome Biology 5(9), R66 (2004)
Tang, S., et al.: Computational method for discovery of estrogen responsive genes. Nucl. Acids Res. 32(21), 6212–6217 (2004)
Carroll, J.S., et al.: Genome-wide analysis of estrogen receptor binding sites. Nat. Genet. 38(11), 1289–1297 (2006)
Halees, A.S., Leyfer, D., Weng, Z.: PromoSer: A large-scale mammalian promoter and transcription start site identification service. Nucleic Acids Res. 31(13), 3554–3559 (2003)
Kel, A.E., et al.: MATCH: A tool for searching transcription factor binding sites in DNA sequences. Nucleic Acids Res. 31(13), 3576–3579 (2003)
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Gong, T. et al. (2008). Sparse Decomposition of Gene Expression Data to Infer Transcriptional Modules Guided by Motif Information. In: Măndoiu, I., Sunderraman, R., Zelikovsky, A. (eds) Bioinformatics Research and Applications. ISBRA 2008. Lecture Notes in Computer Science(), vol 4983. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-79450-9_23
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DOI: https://doi.org/10.1007/978-3-540-79450-9_23
Publisher Name: Springer, Berlin, Heidelberg
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