Probabilistic inference of viral quasispecies subject to recombination

Osvaldo Zagordi, Armin Töpfer, Sandhya Prabhakaran, Volker Roth, Eran Halperin, Niko Beerenwinkel*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

Abstract

RNA viruses are present in a single host as a population of different but related strains. This population, shaped by the combination of genetic change and selection, is called quasispecies. Genetic change is due to both point mutations and recombination events. We present a jumping hidden Markov model that describes the generation of the viral quasispecies and a method to infer its parameters by analysing next generation sequencing data. The model introduces position-specific probability tables over the sequence alphabet to explain the diversity that can be found in the population at each site. Recombination events are indicated by a change of state, allowing a single observed read to originate from multiple sequences. We present an implementation of the EM algorithm to find maximum likelihood estimates of the model parameters and a method to estimate the distribution of viral strains in the quasispecies. The model is validated on simulated data, showing the advantage of explicitly taking the recombination process into account, and applied to reads obtained from two experimental HIV samples.

Original languageEnglish
Title of host publicationResearch in Computational Molecular Biology - 16th Annual International Conference, RECOMB 2012, Proceedings
Pages342-354
Number of pages13
DOIs
StatePublished - 2012
Event16th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2012 - Barcelona, Spain
Duration: 21 Apr 201224 Apr 2012

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume7262 LNBI
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Conference

Conference16th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2012
Country/TerritorySpain
CityBarcelona
Period21/04/1224/04/12

Keywords

  • Hidden Markov model
  • Molecular sequence analysis
  • Next-generation sequencing
  • Sequencing and genotyping technologies
  • Viral quasispecies

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