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Bioinformatics Advance Access originally published online on August 12, 2008
Bioinformatics 2008 24(20):2288-2295; doi:10.1093/bioinformatics/btn420
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

MotifVoter: a novel ensemble method for fine-grained integration of generic motif finders

Edward Wijaya 1,2, Siu-Ming Yiu 3, Ngo Thanh Son 1, Rajaraman Kanagasabai 2 and Wing-Kin Sung 1,4,*

1School of Computing, National University of Singapore, Singapore 119260, 2Institute for Infocomm Research, 21 Heng Mui Keng Terrace, Singapore 119613, 3Department of Computer Science, The University of Hong Kong, Pokfulam Road, Hong Kong and 4Genome Institute of Singapore, 60 Biopolis Street, #02-01 Genome, Singapore 138672

*To whom correspondence should be addressed.


   Abstract

Motivation: Locating transcription factor binding sites (motifs) is a key step in understanding gene regulation. Based on Tompa's benchmark study, the performance of current de novo motif finders is far from satisfactory (with sensitivity ≤0.222 and precision ≤0.307). The same study also shows that no motif finder performs consistently well over all datasets. Hence, it is not clear which finder one should use for a given dataset. To address this issue, a class of algorithms called ensemble methods have been proposed. Though the existing ensemble methods overall perform better than stand-alone motif finders, the improvement gained is not substantial. Our study reveals that these methods do not fully exploit the information obtained from the results of individual finders, resulting in minor improvement in sensitivity and poor precision.

Results: In this article, we identify several key observations on how to utilize the results from individual finders and design a novel ensemble method, MotifVoter, to predict the motifs and binding sites. Evaluations on 186 datasets show that MotifVoter can locate more than 95% of the binding sites found by its component motif finders. In terms of sensitivity and precision, MotifVoter outperforms stand-alone motif finders and ensemble methods significantly on Tompa's benchmark, Escherichia coli, and ChIP-Chip datasets. MotifVoter is available online via a web server with several biologist-friendly features.

Availability: http://www.comp.nus.edu.sg/~bioinfo/MotifVoter

Contact: ksung{at}comp.nus.edu.sg

supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Alex Bateman


Received on May 9, 2008; revised on August 3, 2008; accepted on August 7, 2008

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