Viral quasispecies assembly via maximal clique enumeration.

Virus populations can display high genetic diversity within individual hosts. The intra-host collection of viral haplotypes, called viral quasispecies, is an important determinant of virulence, pathogenesis, and treatment outcome. We present HaploClique, a computational approach to reconstruct the s...

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Autores principales: Armin Töpfer, Tobias Marschall, Rowena A Bull, Fabio Luciani, Alexander Schönhuth, Niko Beerenwinkel
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Publicado: Public Library of Science (PLoS) 2014
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Acceso en línea:https://doaj.org/article/2064e6e3f9d348efb334daaae6663cd3
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spelling oai:doaj.org-article:2064e6e3f9d348efb334daaae6663cd32021-11-18T05:53:02ZViral quasispecies assembly via maximal clique enumeration.1553-734X1553-735810.1371/journal.pcbi.1003515https://doaj.org/article/2064e6e3f9d348efb334daaae6663cd32014-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24675810/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Virus populations can display high genetic diversity within individual hosts. The intra-host collection of viral haplotypes, called viral quasispecies, is an important determinant of virulence, pathogenesis, and treatment outcome. We present HaploClique, a computational approach to reconstruct the structure of a viral quasispecies from next-generation sequencing data as obtained from bulk sequencing of mixed virus samples. We develop a statistical model for paired-end reads accounting for mutations, insertions, and deletions. Using an iterative maximal clique enumeration approach, read pairs are assembled into haplotypes of increasing length, eventually enabling global haplotype assembly. The performance of our quasispecies assembly method is assessed on simulated data for varying population characteristics and sequencing technology parameters. Owing to its paired-end handling, HaploClique compares favorably to state-of-the-art haplotype inference methods. It can reconstruct error-free full-length haplotypes from low coverage samples and detect large insertions and deletions at low frequencies. We applied HaploClique to sequencing data derived from a clinical hepatitis C virus population of an infected patient and discovered a novel deletion of length 357±167 bp that was validated by two independent long-read sequencing experiments. HaploClique is available at https://github.com/armintoepfer/haploclique. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2-5.Armin TöpferTobias MarschallRowena A BullFabio LucianiAlexander SchönhuthNiko BeerenwinkelPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 10, Iss 3, p e1003515 (2014)
institution DOAJ
collection DOAJ
language EN
topic Biology (General)
QH301-705.5
spellingShingle Biology (General)
QH301-705.5
Armin Töpfer
Tobias Marschall
Rowena A Bull
Fabio Luciani
Alexander Schönhuth
Niko Beerenwinkel
Viral quasispecies assembly via maximal clique enumeration.
description Virus populations can display high genetic diversity within individual hosts. The intra-host collection of viral haplotypes, called viral quasispecies, is an important determinant of virulence, pathogenesis, and treatment outcome. We present HaploClique, a computational approach to reconstruct the structure of a viral quasispecies from next-generation sequencing data as obtained from bulk sequencing of mixed virus samples. We develop a statistical model for paired-end reads accounting for mutations, insertions, and deletions. Using an iterative maximal clique enumeration approach, read pairs are assembled into haplotypes of increasing length, eventually enabling global haplotype assembly. The performance of our quasispecies assembly method is assessed on simulated data for varying population characteristics and sequencing technology parameters. Owing to its paired-end handling, HaploClique compares favorably to state-of-the-art haplotype inference methods. It can reconstruct error-free full-length haplotypes from low coverage samples and detect large insertions and deletions at low frequencies. We applied HaploClique to sequencing data derived from a clinical hepatitis C virus population of an infected patient and discovered a novel deletion of length 357±167 bp that was validated by two independent long-read sequencing experiments. HaploClique is available at https://github.com/armintoepfer/haploclique. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2-5.
format article
author Armin Töpfer
Tobias Marschall
Rowena A Bull
Fabio Luciani
Alexander Schönhuth
Niko Beerenwinkel
author_facet Armin Töpfer
Tobias Marschall
Rowena A Bull
Fabio Luciani
Alexander Schönhuth
Niko Beerenwinkel
author_sort Armin Töpfer
title Viral quasispecies assembly via maximal clique enumeration.
title_short Viral quasispecies assembly via maximal clique enumeration.
title_full Viral quasispecies assembly via maximal clique enumeration.
title_fullStr Viral quasispecies assembly via maximal clique enumeration.
title_full_unstemmed Viral quasispecies assembly via maximal clique enumeration.
title_sort viral quasispecies assembly via maximal clique enumeration.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/2064e6e3f9d348efb334daaae6663cd3
work_keys_str_mv AT armintopfer viralquasispeciesassemblyviamaximalcliqueenumeration
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AT rowenaabull viralquasispeciesassemblyviamaximalcliqueenumeration
AT fabioluciani viralquasispeciesassemblyviamaximalcliqueenumeration
AT alexanderschonhuth viralquasispeciesassemblyviamaximalcliqueenumeration
AT nikobeerenwinkel viralquasispeciesassemblyviamaximalcliqueenumeration
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