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Nucleic Acids Research 2006 34(Web Server issue):W541-W545; doi:10.1093/nar/gkl342
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© The Author 2006. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org


Article

Composite Module Analyst: identification of transcription factor binding site combinations using genetic algorithm

T. Waleev1, D. Shtokalo1, T. Konovalova2, N. Voss3, E. Cheremushkin1, P. Stegmaier3, O. Kel-Margoulis3, E. Wingender3,4 and A. Kel3,*

1 A.P. Ershov's Institute of Informatics Systems 6, Lavrentiev avenue, 630090 Novosibirsk, Russia 2 Institute of Cytology and Genetics Novosibirsk, Russia 3 BIOBASE GmbH Halchtersche Strasse 33, D-38304 Wolfenbüttel, Germany 4 Department Bioinformatics, UKG/University Göttingen Goldschmidtstr. 1, D-37077 Göttingen, Germany

*To whom correspondence should be addressed. Tel: +49-5331-858441; Fax: +49-5331-858470; Email: alexander.kel{at}biobase-international.com

Received February 15, 2006. Revised March 4, 2006. Accepted April 18, 2006.

Composite Module Analyst (CMA) is a novel software tool aiming to identify promoter-enhancer models based on the composition of transcription factor (TF) binding sites and their pairs. CMA is closely interconnected with the TRANSFAC® database. In particular, CMA uses the positional weight matrix (PWM) library collected in TRANSFAC® and therefore provides the possibility to search for a large variety of different TF binding sites. We model the structure of the long gene regulatory regions by a Boolean function that joins several local modules, each consisting of co-localized TF binding sites. Having as an input a set of co-regulated genes, CMA builds the promoter model and optimizes the parameters of the model automatically by applying a genetic-regression algorithm. We use a multicomponent fitness function of the algorithm which includes several statistical criteria in a weighted linear function. We show examples of successful application of CMA to a microarray data on transcription profiling of TNF-alpha stimulated primary human endothelial cells. The CMA web server is freely accessible at http://www.gene-regulation.com/pub/programs/cma/CMA.html. An advanced version of CMA is also a part of the commercial system ExPlainTM (www.biobase.de) designed for causal analysis of gene expression data.


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