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Nucleic Acids Research 2005 33(15):4899-4913; doi:10.1093/nar/gki791
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Published online 2 September 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oxfordjournals.org

Article

Limitations and potentials of current motif discovery algorithms

Jianjun Hu1,2, Bin Li2 and Daisuke Kihara1,2,3,4,*

1Department of Biological Sciences, College of Science, Purdue University West Lafayette, IN 47907, USA 2Department of Computer Science, College of Science, Purdue University West Lafayette, IN 47907, USA 3Markey Center for Structural Biology, College of Science, Purdue University West Lafayette, IN 47907, USA 4The Bindley Bioscience Center, College of Science, Purdue University West Lafayette, IN 47907, USA

*To whom correspondence should be addressed. Tel: +1 765 496 2284; Fax: +1 765 494 1189; Email: dkihara{at}purdue.edu

Received March 3, 2005. Revised May 21, 2005. Accepted August 9, 2005.

Computational methods for de novo identification of gene regulation elements, such as transcription factor binding sites, have proved to be useful for deciphering genetic regulatory networks. However, despite the availability of a large number of algorithms, their strengths and weaknesses are not sufficiently understood. Here, we designed a comprehensive set of performance measures and benchmarked five modern sequence-based motif discovery algorithms using large datasets generated from Escherichia coli RegulonDB. Factors that affect the prediction accuracy, scalability and reliability are characterized. It is revealed that the nucleotide and the binding site level accuracy are very low, while the motif level accuracy is relatively high, which indicates that the algorithms can usually capture at least one correct motif in an input sequence. To exploit diverse predictions from multiple runs of one or more algorithms, a consensus ensemble algorithm has been developed, which achieved 6–45% improvement over the base algorithms by increasing both the sensitivity and specificity. Our study illustrates limitations and potentials of existing sequence-based motif discovery algorithms. Taking advantage of the revealed potentials, several promising directions for further improvements are discussed. Since the sequence-based algorithms are the baseline of most of the modern motif discovery algorithms, this paper suggests substantial improvements would be possible for them.


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