Bioinformatics Vol. 19 Suppl. 2 2003
pages ii5-ii14
© 2003 Oxford University Press
Computational detection of cis -regulatory modules
1 Department of Electrical Engineering ESAT-SCD, Katholieke Universiteit Leuven, Kasteelpark Arenberg 10, Leuven, 3001, Belgium
Received on March 17, 2003
; accepted on June 9, 2003
Motivation: The transcriptional regulation of a metazoan gene depends on the cooperative action of multiple transcription factors that bind to cis-regulatory modules (CRMs) located in the neighborhood of the gene. By integrating multiple signals, CRMs confer an organism specific spatial and temporal rate of transcription.
Results: Based on the hypothesis that genes that are needed in exactly the same conditions might share similar regulatory switches, we have developed a novel methodology to find CRMs in a set of coexpressed or coregulated genes. The ModuleSearcher algorithm finds for a given gene set the best scoring combination of transcription factor binding sites within a sequence window using an A*procedure for tree searching. To keep the level of noise low, we use DNA sequences that are most likely to contain functional cis-regulatory information, namely conserved regions between human and mouse orthologous genes. The ModuleScanner performs genomic searches with a predicted CRM or with a user-defined CRM known from the literature to find possible target genes. The validity of a set of putative targets is checked using Gene Ontology annotations. We demonstrate the use and effectiveness of the ModuleSearcher and ModuleScanner algorithms and test their specificity and sensitivity on semi-artificial data. Next, we search for a module in a cluster of gene expression profiles of human cell cycle genes.
Availability: The ModuleSearcher is available as a web service within the TOUCAN workbench for regulatory sequence analysis, which can be downloaded from http://www.esat.kuleuven.ac.be/~dna/BioI.
Contact: stein.aerts{at}esat.kuleuven.ac.be
* To whom correspondence should be addressed.
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