Identifying novel constrained elements by exploiting biased substitution patterns
Name
Garber-2009-dentifying novel constrained elements.pdf
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Author(s)
Guttman, Mitchell
Garber, Manuel
Clamp, Michele
Zody, Michael C.
Friedman, Nir
Xie, Xiaohui
Date Issued
June 2009
Journal
Bioinformatics
Publisher
Oxford University Press (OUP)
Citation
Garber, M. et al. “Identifying Novel Constrained Elements by Exploiting Biased Substitution Patterns.” Bioinformatics 25.12 (2009): i54–i62.
Version
Final published version
Abstract
Motivation: Comparing the genomes from closely related species provides a powerful tool to identify functional elements in a reference genome. Many methods have been developed to identify conserved sequences across species; however, existing methods only model conservation as a decrease in the rate of mutation and have ignored selection acting on the pattern of mutations.
Results: We present a new approach that takes advantage of deeply sequenced clades to identify evolutionary selection by uncovering not only signatures of rate-based conservation but also substitution patterns characteristic of sequence undergoing natural selection. We describe a new statistical method for modeling biased nucleotide substitutions, a learning algorithm for inferring site-specific substitution biases directly from sequence alignments and a hidden Markov model for detecting constrained elements characterized by biased substitutions. We show that the new approach can identify significantly more degenerate constrained sequences than rate-based methods. Applying it to the ENCODE regions, we identify as much as 10.2% of these regions are under selection.
Availability: The algorithms are implemented in a Java software package, called SiPhy, freely available at http://www.broadinstitute.org/science/software/.
Contact: xhx@ics.uci.edu
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution Non-Commercial
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DOI of Published Version
https://doi.org/10.1093/bioinformatics/btp190
