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Nucleic Acids Research 2005 33(7):2290-2301; doi:10.1093/nar/gki519
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Published online 22 April 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
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Article

Computational technique for improvement of the position-weight matrices for the DNA/protein binding sites

Naum I. Gershenzon*, Gary D. Stormo1 and Ilya P. Ioshikhes

Department of Biomedical Informatics, The Ohio State University 3184 Graves Hall, 333 W. 10th Avenue, Columbus, OH 43210, USA 1Department of Genetics, Washington University Medical School 660 S. Euclid Avenue, Box 8232 St Louis, MO 63110, USA

*To whom correspondence should be addressed. Tel: +1 614 688 3236; Fax: +1 614 688 6600; Email: gershenzon-1{at}medctr.osu.edu

Received December 9, 2004. Revised February 24, 2005. Accepted March 29, 2005.

Position-weight matrices (PWMs) are broadly used to locate transcription factor binding sites in DNA sequences. The majority of existing PWMs provide a low level of both sensitivity and specificity. We present a new computational algorithm, a modification of the Staden–Bucher approach, that improves the PWM. We applied the proposed technique on the PWM of the GC-box, binding site for Sp1. The comparison of old and new PWMs shows that the latter increase both sensitivity and specificity. The statistical parameters of GC-box distribution in promoter regions and in the human genome, as well as in each chromosome, are presented. The majority of commonly used PWMs are the 4-row mononucleotide matrices, although 16-row dinucleotide matrices are known to be more informative. The algorithm efficiently determines the 16-row matrices and preliminary results show that such matrices provide better results than 4-row matrices.


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