Hidden Markov models for evolution and comparative genomics analysis

PLoS One. 2013 Jun 7;8(6):e65012. doi: 10.1371/journal.pone.0065012. Print 2013.

Abstract

The problem of reconstruction of ancestral states given a phylogeny and data from extant species arises in a wide range of biological studies. The continuous-time Markov model for the discrete states evolution is generally used for the reconstruction of ancestral states. We modify this model to account for a case when the states of the extant species are uncertain. This situation appears, for example, if the states for extant species are predicted by some program and thus are known only with some level of reliability; it is common for bioinformatics field. The main idea is formulation of the problem as a hidden Markov model on a tree (tree HMM, tHMM), where the basic continuous-time Markov model is expanded with the introduction of emission probabilities of observed data (e.g. prediction scores) for each underlying discrete state. Our tHMM decoding algorithm allows us to predict states at the ancestral nodes as well as to refine states at the leaves on the basis of quantitative comparative genomics. The test on the simulated data shows that the tHMM approach applied to the continuous variable reflecting the probabilities of the states (i.e. prediction score) appears to be more accurate then the reconstruction from the discrete states assignment defined by the best score threshold. We provide examples of applying our model to the evolutionary analysis of N-terminal signal peptides and transcription factor binding sites in bacteria. The program is freely available at http://bioinf.fbb.msu.ru/~nadya/tHMM and via web-service at http://bioinf.fbb.msu.ru/treehmmweb.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Asparaginase / metabolism
  • Bayes Theorem
  • Binding Sites
  • Biological Evolution*
  • Computer Simulation
  • Genomics*
  • Markov Chains*
  • Models, Genetic*
  • Phylogeny
  • Protein Sorting Signals / genetics
  • Transcription Factors / metabolism

Substances

  • Protein Sorting Signals
  • Transcription Factors
  • Asparaginase

Grants and funding

The work was supported by Russian Ministry of Education and Science (State contract No 07.514.11.4007, http://eng.mon.gov.ru/) and Russian Foundation for Basic Research (grant 11-04-02016-a to AF, by the Johns Hopkins University Framework for the Future (AF), and by the Commonwealth Foundation (AF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.