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Probabilistic Inference of Viral Quasispecies Subject to Recombination

RNA viruses exist in their hosts as populations of different but related strains. The virus population, often called quasispecies, is shaped by a combination of genetic change and natural selection. Genetic change is due to both point mutations and recombination events. We present a jumping hidden M...

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Main Authors: Töpfer, Armin, Zagordi, Osvaldo, Prabhakaran, Sandhya, Roth, Volker, Halperin, Eran, Beerenwinkel, Niko
Formato: Artigo
Idioma:Inglês
Publicado em: Mary Ann Liebert, Inc. 2013
Assuntos:
Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC3576916/
https://ncbi.nlm.nih.gov/pubmed/23383997
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1089/cmb.2012.0232
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spelling pubmed-35769162014-02-01 Probabilistic Inference of Viral Quasispecies Subject to Recombination Töpfer, Armin Zagordi, Osvaldo Prabhakaran, Sandhya Roth, Volker Halperin, Eran Beerenwinkel, Niko J Comput Biol Research Articles RNA viruses exist in their hosts as populations of different but related strains. The virus population, often called quasispecies, is shaped by a combination of genetic change and natural selection. Genetic change is due to both point mutations and recombination events. We present a jumping hidden Markov model that describes the generation of viral quasispecies and a method to infer its parameters from 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 a specific implementation of the expectation maximization (EM) algorithm to find maximum a posteriori 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 a clinical HIV sample. Mary Ann Liebert, Inc. 2013-02 /pmc/articles/PMC3576916/ /pubmed/23383997 http://dx.doi.org/10.1089/cmb.2012.0232 Text en Copyright 2013, Mary Ann Liebert, Inc.
institution US NLM
collection PubMed Central
language Inglês
format Artigo
topic Research Articles
spellingShingle Research Articles
Töpfer, Armin
Zagordi, Osvaldo
Prabhakaran, Sandhya
Roth, Volker
Halperin, Eran
Beerenwinkel, Niko
Probabilistic Inference of Viral Quasispecies Subject to Recombination
description RNA viruses exist in their hosts as populations of different but related strains. The virus population, often called quasispecies, is shaped by a combination of genetic change and natural selection. Genetic change is due to both point mutations and recombination events. We present a jumping hidden Markov model that describes the generation of viral quasispecies and a method to infer its parameters from 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 a specific implementation of the expectation maximization (EM) algorithm to find maximum a posteriori 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 a clinical HIV sample.
author Töpfer, Armin
Zagordi, Osvaldo
Prabhakaran, Sandhya
Roth, Volker
Halperin, Eran
Beerenwinkel, Niko
author_facet Töpfer, Armin
Zagordi, Osvaldo
Prabhakaran, Sandhya
Roth, Volker
Halperin, Eran
Beerenwinkel, Niko
author_sort Töpfer, Armin
title Probabilistic Inference of Viral Quasispecies Subject to Recombination
title_short Probabilistic Inference of Viral Quasispecies Subject to Recombination
title_full Probabilistic Inference of Viral Quasispecies Subject to Recombination
title_fullStr Probabilistic Inference of Viral Quasispecies Subject to Recombination
title_full_unstemmed Probabilistic Inference of Viral Quasispecies Subject to Recombination
title_sort probabilistic inference of viral quasispecies subject to recombination
publisher Mary Ann Liebert, Inc.
publishDate 2013
url https://ncbi.nlm.nih.gov/pmc/articles/PMC3576916/
https://ncbi.nlm.nih.gov/pubmed/23383997
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1089/cmb.2012.0232
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