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Full-length haplotype reconstruction to infer the structure of heterogeneous virus populations

Giallonardo, Francesca Di and Töpfer, Armin and Rey, Melanie and Prabhakaran, Sandhya and Duport, Yannick and Leemann, Christine and Schmutz, Stefan and Campbell, Nottania K. and Joos, Beda and Lecca, Maria Rita and Patrignani, Andrea and Däumer, Martin and Beisel, Christian and Rusert, Peter and Trkola, Alexandra and Günthard, Huldrych F. and Roth, Volker and Beerenwinkel, Niko and Metzner, Karin J.. (2014) Full-length haplotype reconstruction to infer the structure of heterogeneous virus populations. Nucleic Acids Research, 42 (14). e115.

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Abstract

Next-generation sequencing (NGS) technologies enable new insights into the diversity of virus populations within their hosts. Diversity estimation is currently restricted to single-nucleotide variants or to local fragments of no more than a few hundred nucleotides defined by the length of sequence reads. To study complex heterogeneous virus populations comprehensively, novel methods are required that allow for complete reconstruction of the individual viral haplotypes. Here, we show that assembly of whole viral genomes of ∼8600 nucleotides length is feasible from mixtures of heterogeneous HIV-1 strains derived from defined combinations of cloned virus strains and from clinical samples of an HIV-1 superinfected individual. Haplotype reconstruction was achieved using optimized experimental protocols and computational methods for amplification, sequencing and assembly. We comparatively assessed the performance of the three NGS platforms 454 Life Sciences/Roche, Illumina and Pacific Biosciences for this task. Our results prove and delineate the feasibility of NGS-based full-length viral haplotype reconstruction and provide new tools for studying evolution and pathogenesis of viruses.
Faculties and Departments:05 Faculty of Science > Departement Mathematik und Informatik > Informatik > Datenanalyse (Roth)
UniBasel Contributors:Roth, Volker
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Oxford University Press
ISSN:0305-1048
e-ISSN:1362-4962
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:10 Oct 2017 08:35
Deposited On:06 Feb 2015 09:58

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