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Bioinformatics Advance Access published online on August 27, 2004

Bioinformatics, doi:10.1093/bioinformatics/bth471
Bioinformatics © Oxford University Press 2004; all rights reserved
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Received September 11, 2003
Revised July 26, 2004
Accepted August 7, 2004

Article

DWE: discriminating word enumerator

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

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

* To whom correspondence should be addressed. E-mail: ps{at}cs.pdx.edu.


   Abstract

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 over-represented 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 over represented 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/EBP{beta}) are the most over represented in proximal promoters of liver-specific genes. Our results suggest that HNF-4 has strong synergistic relationships with hepatocyte nuclear factors HNF-1, HNF-4 and HNF-3{beta} and with C/EBP{beta}.

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

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


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