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dc.contributor.authorPhilippakis, Anthony Andrew
dc.contributor.authorBusser, Brian W
dc.contributor.authorGisselbrecht, Stephen S
dc.contributor.authorHe, Fangxue Sherry
dc.contributor.authorEstrada, Beatriz
dc.contributor.authorMichelson, Alan D
dc.contributor.authorBulyk, Martha Leonia
dc.date.accessioned2011-04-18T02:00:53Z
dc.date.issued2006
dc.identifier.citationPhilippakis, Anthony A., Brian W. Busser, Stephen S. Gisselbrecht, Fangxue Sherry He, Beatriz Estrada, Alan M. Michelson, and Martha L. Bulyk. 2006. Expression-guided in silico evaluation of candidate Cis regulatory codes for drosophila muscle founder cells. PLoS Computational Biology 2(5): e53.en_US
dc.identifier.issn1553-734Xen_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4853403
dc.description.abstractWhile combinatorial models of transcriptional regulation can be inferred for metazoan systems from a priori biological knowledge, validation requires extensive and time-consuming experimental work. Thus, there is a need for computational methods that can evaluate hypothesized cis regulatory codes before the difficult task of experimental verification is undertaken. We have developed a novel computational framework (termed “CodeFinder”) that integrates transcription factor binding site and gene expression information to evaluate whether a hypothesized transcriptional regulatory model (TRM; i.e., a set of co-regulating transcription factors) is likely to target a given set of co-expressed genes. Our basic approach is to simultaneously predict cis regulatory modules (CRMs) associated with a given gene set and quantify the enrichment for combinatorial subsets of transcription factor binding site motifs comprising the hypothesized TRM within these predicted CRMs. As a model system, we have examined a TRM experimentally demonstrated to drive the expression of two genes in a sub-population of cells in the developing Drosophila mesoderm, the somatic muscle founder cells. This TRM was previously hypothesized to be a general mode of regulation for genes expressed in this cell population. In contrast, the present analyses suggest that a modified form of this cis regulatory code applies to only a subset of founder cell genes, those whose gene expression responds to specific genetic perturbations in a similar manner to the gene on which the original model was based. We have confirmed this hypothesis by experimentally discovering six (out of 12 tested) new CRMs driving expression in the embryonic mesoderm, four of which drive expression in founder cells.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pcbi.0020053en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1464814/pdf/en_US
dash.licenseLAA
dc.titleExpression-Guided in Silico Evaluation of Candidate Cis Regulatory Codes for Drosophila Muscle Founder Cellsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Computational Biologyen_US
dash.depositing.authorPhilippakis, Anthony Andrew
dc.date.available2011-04-18T02:00:53Z
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Pediatrics-Children's Hospitalen_US
dash.affiliation.otherHMS^Pathologyen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dc.identifier.doi10.1371/journal.pcbi.0020053*
dash.contributor.affiliatedPhilippakis, Anthony Andrew
dash.contributor.affiliatedMichelson, Alan
dash.contributor.affiliatedBulyk, Martha


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