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Bioinformatics Advance Access originally published online on August 27, 2004
Bioinformatics 2005 21(1):31-38; doi:10.1093/bioinformatics/bth471
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Bioinformatics vol. 21 issue 1 © Oxford University Press 2005; all rights reserved.

DWE: Discriminating Word Enumerator

Pavel Sumazin 1,2,*, Gengxin Chen 1, Naoya Hata 1, Andrew D. Smith 1, Theresa Zhang 3 and Michael Q. Zhang 1,*

1 Cold Spring Harbor Laboratory 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
2 Computer Science Department, Portland State University P.O. Box 751, Portland, OR 97207, USA
3 Bioinformatics, Merck Research Laboratories Rahway, NJ 07065, USA

*To whom correspondence should be addressed.

Motivation: Tissue-specific transcription factor binding sites give insight into tissue-specific transcription regulation.

Results: We describe a word-counting-based tool for de novo tissue-specific transcription factor binding site discovery using expression information in addition to sequence information. We incorporate tissue-specific gene expression through gene classification to positive expression and repressed expression. We present a direct statistical approach to find overrepresented transcription factor binding sites in a foreground promoter sequence set against a background promoter sequence set. Our approach naturally extends to synergistic transcription factor binding site search.

We find putative transcription factor binding sites that are overrepresented in the proximal promoters of liver-specific genes relative to proximal promoters of liver-independent genes. Our results indicate that binding sites for hepatocyte nuclear factors (especially HNF-1 and HNF-4) and CCAAT/enhancer-binding protein (C/EBPß) are the most overrepresented in proximal promoters of liver-specific genes. Our results suggest that HNF-4 has strong synergistic relationships with HNF-1, HNF-4 and HNF-3ß and with C/EBPß.

Availability: Programs are available for use over the Web at http://rulai.cshl.edu/tools/dwe

Contact: ps{at}cs.pdx.edu; mzhang{at}cshl.edu

Supplementary information: Data and omitted results are available at http://rulai.cshl.edu/tools/dwe/supp

Received on September 11, 2003; revised on July 26, 2004; accepted on August 7, 2004

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