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

DOI10.1214/07-AOAS103zbMATH Open1129.62111arXiv0708.4318OpenAlexW2021723272MaRDI QIDQ995727FDOQ995727

Authors: Qing Zhou, Wing H. Wong 

Publication date: 10 September 2007

Published in: The Annals of Applied Statistics (Search for Journal in Brave)

Abstract: 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.

Full work available at URL: https://arxiv.org/abs/0708.4318

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zbMATH Keywords

dynamic programmingcomparative genomicsmotiv discovery

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) Numerical analysis or methods applied to Markov chains (65C40) Biochemistry, molecular biology (92C40)

Cited In (9)

• Assessing multivariate predictors of financial market movements: A latent factor framework for ordinal data
• Transcription factor binding site prediction with multivariate gene expression data
• Finding transcription factor binding motifs for coregulated genes by combining sequence overrepresentation with cross-species conservation
• Extended sunflower hidden Markov models for the recognition of homotypic cis-regulatory modules
• Discovering cis-regulatory modules by optimizing barbecues
• Identifying potential regulatory elements by transcription factor binding site alignment using partial order graphs
• A novel pairwise comparison method for in silico discovery of statistically significant cis-regulatory elements in eukaryotic promoter regions: application to \textit{Arabidopsis}
• Heterogeneity in DNA multiple alignments: modeling, inference, and applications in motif finding
• SegHMC: an algorithm for discovery of cis-regulatory module based on segmental HMM

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