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Nucleic Acids Research 2004 32(13):3826-3835; doi:10.1093/nar/gkh713
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Published online 20 July 2004

Nucleic Acids Research, Vol. 32 No. 13 © Oxford University Press 2004; all rights reserved

Discovery of sequence motifs related to coexpression of genes using evolutionary computation

Gary B. Fogel, Dana G. Weekes, Gabor Varga1, Ernst R. Dow1, Harry B. Harlow1, Jude E. Onyia1 and Chen Su1,*

Natural Selection, Inc., 3333 N. Torrey Pines Ct., Suite 200, La Jolla, CA 92037, USA and 1 Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA

* To whom correspondence should be addressed. Tel: +1 317 277 9657; Fax: +1 317 276 6009; Email: chen_su{at}lilly.com

Received April 21, 2004; Revised May 28, 2004; Accepted July 1, 2004

Transcription factors are key regulatory elements that control gene expression. Recognition of transcription factor binding site (TFBS) motifs in the upstream region of coexpressed genes is therefore critical towards a true understanding of the regulations of gene expression. The task of discovering eukaryotic TFBSs remains a challenging problem. Here, we demonstrate that evolutionary computation can be used to search for TFBSs in upstream regions of genes known to be coexpressed. Evolutionary computation was used to search for TFBSs of genes regulated by octamer-binding factor and nuclear factor kappa B. The discovered binding sites included experimentally determined known binding motifs as well as lists of putative, previously unknown TFBSs. We believe that this method to search nucleotide sequence information efficiently for similar motifs will be useful for discovering TFBSs that affect gene regulation.


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