Computational technique for improvement of the position-weight matrices for the DNA/protein binding sites.
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.
Gershenzon
Naum I
NI
Department of Biomedical Informatics, The Ohio State University 3184 Graves Hall, 333 W. 10th Avenue, Columbus, OH 43210, USA. gershenzon-1@medctr.osu.edu
Stormo
Gary D
GD
Ioshikhes
Ilya P
IP
D000465:Algorithms; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015894:Genome, Human; D006801:Humans; D011401:Promoter Regions, Genetic; D020218:Response Elements; D017422:Sequence Analysis, DNA / Q000379:methods*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors