Computing exact P-values for DNA motifs

• Published in: Bioinformatics Vol. 23; no. 5; pp. 531 - 537
• Main Authors: Zhang, Jing, Jiang, Bo, Li, Ming, Tromp, John, Zhang, Xuegong, Zhang, Michael Q.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2007; Oxford Publishing Limited (England)
• Subjects: Algorithms; Binding Sites; Bioinformatics; Biological and medical sciences; Computer Simulation; Deoxyribonucleic acid; DNA; Fundamental and applied biological sciences. Psychology; General aspects; Mathematics in biology. Statistical analysis. Models. Metrology. Data processing in biology (general aspects); Models, Statistical; Promoter Regions, Genetic; Sequence Analysis, DNA - methods; Software; Transcription Factors - metabolism; Original document; Computer program; DNA; Models; Rank; Binding site; C++ language; Markov model; Dynamic programming; Transcription factor; Bioinformatics; Pattern analysis
• ISSN: 1367-4803; 1367-4811; 1367-4811; 1460-2059
• DOI: 10.1093/bioinformatics/btl662

Motivation: Many heuristic algorithms have been designed to approximate P-values of DNA motifs described by position weight matrices, for evaluating their statistical significance. They often significantly deviate from the true P-value by orders of magnitude. Exact P-value computation is needed for ranking the motifs. Furthermore, surprisingly, the complexity of the problem is unknown. Results: We show the problem to be NP-hard, and present MotifRank, software based on dynamic programming, to calculate exact P-values of motifs. We define the exact P-value on a general and more precise model. Asymptotically, MotifRank is faster than the best exact P-value computing algorithm, and is in fact practical. Our experiments clearly demonstrate that MotifRank significantly improves the accuracy of existing approximation algorithms. Availability: MotifRank is available from http://bio.dlg.cn Contact: mzhang@cshl.edumli@uwaterloo.ca Supplementary information: Supplementary data are available at Bioinformatics online.