Bioinformatics Advance Access originally published online on January 29, 2004
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Bioinformatics 20(6) © Oxford University Press 2004; all rights reserved.
Modeling within-motif dependence for transcription factor binding site predictions
Department of Statistics, Harvard University, 1 Oxford ST, Cambridge, MA 02138, USA
Received on August 28, 2003
; revised on October 31, 2003
; accepted on November 3, 2003
Advance Access Publication January 29, 2004
Motivation: The position-specific weight matrix (PWM) model, which assumes that each position in the DNA site contributes independently to the overall protein–DNA interaction, has been the primary means to describe transcription factor binding site motifs. Recent biological experiments, however, suggest that there exists interdependence among positions in the binding sites. In order to exploit this interdependence to aid motif discovery, we extend the PWM model to include pairs of correlated positions and design a Markov chain Monte Carlo algorithm to sample in the model space. We then combine the model sampling step with the Gibbs sampling framework for de novo motif discoveries.
Results: Testing on experimentally validated binding sites, we find that about 25% of the transcription factor binding motifs show significant within-site position correlations, and 80% of these motif models can be improved by considering the correlated positions. Using both simulated data and real promoter sequences, we show that the new de novo motif-finding algorithm can infer the true correlated position pairs accurately and is more precise in finding putative transcription factor binding sites than the standard Gibbs sampling algorithms.
Availability: The program is available at http://www.people.fas.harvard.edu/~junliu/
Contact: jliu{at}stat.harvard.edu
* To whom correspondence should be addressed.
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