Modeling the evolution of regulatory elements by simultaneous detection and alignment with phylogenetic pair HMMs.

Loading...
Thumbnail Image

Date

2010-12-16

Journal Title

Journal ISSN

Volume Title

Repository Usage Stats

216
views
184
downloads

Citation Stats

Abstract

The computational detection of regulatory elements in DNA is a difficult but important problem impacting our progress in understanding the complex nature of eukaryotic gene regulation. Attempts to utilize cross-species conservation for this task have been hampered both by evolutionary changes of functional sites and poor performance of general-purpose alignment programs when applied to non-coding sequence. We describe a new and flexible framework for modeling binding site evolution in multiple related genomes, based on phylogenetic pair hidden Markov models which explicitly model the gain and loss of binding sites along a phylogeny. We demonstrate the value of this framework for both the alignment of regulatory regions and the inference of precise binding-site locations within those regions. As the underlying formalism is a stochastic, generative model, it can also be used to simulate the evolution of regulatory elements. Our implementation is scalable in terms of numbers of species and sequence lengths and can produce alignments and binding-site predictions with accuracy rivaling or exceeding current systems that specialize in only alignment or only binding-site prediction. We demonstrate the validity and power of various model components on extensive simulations of realistic sequence data and apply a specific model to study Drosophila enhancers in as many as ten related genomes and in the presence of gain and loss of binding sites. Different models and modeling assumptions can be easily specified, thus providing an invaluable tool for the exploration of biological hypotheses that can drive improvements in our understanding of the mechanisms and evolution of gene regulation.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1371/journal.pcbi.1001037

Publication Info

Majoros, William H, and Uwe Ohler (2010). Modeling the evolution of regulatory elements by simultaneous detection and alignment with phylogenetic pair HMMs. PLoS Comput Biol, 6(12). p. e1001037. 10.1371/journal.pcbi.1001037 Retrieved from https://hdl.handle.net/10161/4455.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Majoros

William Majoros

Assistant Professor of Biostatistics & Bioinformatics

William H. Majoros, PhD, is an Assistant Professor of Biostatistics and Bioinformatics.

Ohler

Uwe Ohler

Adjunct Associate Professor in the Department of Biostatistics & Bioinformatics

Computational Biology of Gene Regulation
Sequence Analysis
Image Expression Analysis
Applied Machine Learning


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.