Bioinformatics Advance Access originally published online on June 5, 2008
Bioinformatics 2008 24(15):1669-1675; doi:10.1093/bioinformatics/btn254
Modeling promoter grammars with evolving hidden Markov models
The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen N, Denmark
*To whom correspondence should be addressed.
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Abstract |
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Motivation: Describing and modeling biological features of eukaryotic promoters remains an important and challenging problem within computational biology. The promoters of higher eukaryotes in particular display a wide variation in regulatory features, which are difficult to model. Often several factors are involved in the regulation of a set of co-regulated genes. If so, promoters can be modeled with connected regulatory features, where the network of connections is characteristic for a particular mode of regulation.
Results: With the goal of automatically deciphering such regulatory structures, we present a method that iteratively evolves an ensemble of regulatory grammars using a hidden Markov Model (HMM) architecture composed of interconnected blocks representing transcription factor binding sites (TFBSs) and background regions of promoter sequences. The ensemble approach reduces the risk of overfitting and generally improves performance. We apply this method to identify TFBSs and to classify promoters preferentially expressed in macrophages, where it outperforms other methods due to the increased predictive power given by the grammar.
Availability: The software and the datasets are available from http://modem.ucsd.edu/won/eHMM.tar.gz
Contact: krogh{at}binf.ku.dk
Supplementary information: Supplementary data are available at Bioinformatics online.
Associate Editor: Alex Bateman
Present address: Department of Chemistry & Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0359, USA.
Received on January 28, 2008; revised on April 28, 2008; accepted on May 30, 2008
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