Phylogeny based discovery of regulatory elements. Export

@article{citeulike:882012, abstract = {BACKGROUND: Algorithms that locate evolutionarily conserved sequences have become powerful tools for finding functional DNA elements, including transcription factor binding sites; however, most methods do not take advantage of an explicit model for the constrained evolution of functional DNA sequences. RESULTS: We developed a probabilistic framework that combines an HKY85 model, which assigns probabilities to different base substitutions between species, and weight matrix models of transcription factor binding sites, which describe the probabilities of observing particular nucleotides at specific positions in the binding site. The method incorporates the phylogenies of the species under consideration and takes into account the position specific variation of transcription factor binding sites. Using our framework we assessed the suitability of alignments of genomic sequences from commonly used species as substrates for comparative genomic approaches to regulatory motif finding. We then applied this technique to Saccharomyces cerevisiae and related species by examining all possible six base pair DNA sequences (hexamers) and identifying sequences that are conserved in a significant number of promoters. By combining similar conserved hexamers we reconstructed known cis-regulatory motifs and made predictions of previously unidentified motifs. We tested one prediction experimentally, finding it to be a regulatory element involved in the transcriptional response to glucose. CONCLUSION: The experimental validation of a regulatory element prediction missed by other large-scale motif finding studies demonstrates that our approach is a useful addition to the current suite of tools for finding regulatory motifs.}, address = {Department of Genetics, Washington University School of Medicine, 4444 Forest Park Parkway, St. Louis, MO 63108, USA. jgertz@genetics.wustl.edu}, author = {Gertz, J. and Fay, J. C. and Cohen, B. A.}, citeulike-article-id = {882012}, citeulike-linkout-0 = {http://dx.doi.org/10.1186/1471-2105-7-266}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16716228}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16716228}, doi = {10.1186/1471-2105-7-266}, issn = {1471-2105}, journal = {BMC Bioinformatics}, keywords = {crm, footprinting, hky85, motif, phylogeny, pwm, regulation, tfbs}, posted-at = {2009-05-23 05:26:04}, priority = {2}, title = {Phylogeny based discovery of regulatory elements.}, url = {http://dx.doi.org/10.1186/1471-2105-7-266}, volume = {7}, year = {2006} }

TY - JOUR ID - citeulike:882012 L3 - citeulike-article-id:882012 N2 - BACKGROUND: Algorithms that locate evolutionarily conserved sequences have become powerful tools for finding functional DNA elements, including transcription factor binding sites; however, most methods do not take advantage of an explicit model for the constrained evolution of functional DNA sequences. RESULTS: We developed a probabilistic framework that combines an HKY85 model, which assigns probabilities to different base substitutions between species, and weight matrix models of transcription factor binding sites, which describe the probabilities of observing particular nucleotides at specific positions in the binding site. The method incorporates the phylogenies of the species under consideration and takes into account the position specific variation of transcription factor binding sites. Using our framework we assessed the suitability of alignments of genomic sequences from commonly used species as substrates for comparative genomic approaches to regulatory motif finding. We then applied this technique to Saccharomyces cerevisiae and related species by examining all possible six base pair DNA sequences (hexamers) and identifying sequences that are conserved in a significant number of promoters. By combining similar conserved hexamers we reconstructed known cis-regulatory motifs and made predictions of previously unidentified motifs. We tested one prediction experimentally, finding it to be a regulatory element involved in the transcriptional response to glucose. CONCLUSION: The experimental validation of a regulatory element prediction missed by other large-scale motif finding studies demonstrates that our approach is a useful addition to the current suite of tools for finding regulatory motifs. JF - BMC Bioinformatics SN - 1471-2105 AD - Department of Genetics, Washington University School of Medicine, 4444 Forest Park Parkway, St. Louis, MO 63108, USA. jgertz@genetics.wustl.edu TI - Phylogeny based discovery of regulatory elements. VL - 7 KW - crm KW - footprinting KW - hky85 KW - motif KW - phylogeny KW - pwm KW - regulation KW - tfbs AU - Gertz, J AU - Fay, JC AU - Cohen, BA PY - 2006/// UR - http://dx.doi.org/10.1186/1471-2105-7-266 ER -