Coupling hidden Markov models for the discovery of Cis-regulatory modules in multiple species

Details Coupling hidden Markov models for the discovery of Cis-regulatory modules in multiple species Coupling hidden Markov models for the discovery of Cis-regulatory modules in multiple species

2007-08-31

arxiv.org/abs/0708.4318v1

Annals of Applied Statistics 2007, Vol. 1, No. 1, 36-65

Statistics

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Published at http://dx.doi.org/10.1214/07-AOAS103 in the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Ins

Scientific paper

10.1214/07-AOAS103

Cis-regulatory modules (CRMs) composed of multiple transcription factor binding sites (TFBSs) control gene expression in eukaryotic genomes. Comparative genomic studies have shown that these regulatory elements are more conserved across species due to evolutionary constraints. We propose a statistical method to combine module structure and cross-species orthology in de novo motif discovery. We use a hidden Markov model (HMM) to capture the module structure in each species and couple these HMMs through multiple-species alignment. Evolutionary models are incorporated to consider correlated structures among aligned sequence positions across different species. Based on our model, we develop a Markov chain Monte Carlo approach, MultiModule, to discover CRMs and their component motifs simultaneously in groups of orthologous sequences from multiple species. Our method is tested on both simulated and biological data sets in mammals and Drosophila, where significant improvement over other motif and module discovery methods is observed.

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