Bayesian genome assembly and assessment by markov chain monte carlo sampling

PLoS One. 2014 Jun 26;9(6):e99497. doi: 10.1371/journal.pone.0099497. eCollection 2014.

Abstract

Most genome assemblers construct point estimates, choosing only a single genome sequence from among many alternative hypotheses that are supported by the data. We present a Markov chain Monte Carlo approach to sequence assembly that instead generates distributions of assembly hypotheses with posterior probabilities, providing an explicit statistical framework for evaluating alternative hypotheses and assessing assembly uncertainty. We implement this approach in a prototype assembler, called Genome Assembly by Bayesian Inference (GABI), and illustrate its application to the bacteriophage [Formula: see text]X174. Our sampling strategy achieves both good mixing and convergence on Illumina test data for [Formula: see text]X174, demonstrating the feasibility of our approach. We summarize the posterior distribution of assembly hypotheses generated by GABI as a majority-rule consensus assembly. Then we compare the posterior distribution to external assemblies of the same test data, and annotate those assemblies by assigning posterior probabilities to features that are in common with GABI's assembly graph. GABI is freely available under a GPL license from https://bitbucket.org/mhowison/gabi.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteriophage phi X 174 / genetics*
  • Contig Mapping / methods*
  • Genome, Viral*
  • Probability
  • Software*

Grants and funding

This work was supported by the National Science Foundation (http://www.nsf.gov) through the Alan T. Waterman Award to CWD and award DEB-1026611 to EJE, and through additional support from the Brown Division of Biology and Medicine (http://biomed.brown.edu) to EJE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.