Full-length Haplotype Reconstruction to Infer the Structure of Heterogeneous Virus Populations

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2014 Jun 29

PMID 24972832

Citations 66

Authors

Francesca Di Giallonardo

Armin Topfer

Melanie Rey

Sandhya Prabhakaran

Yannick Duport

Christine Leemann

Stefan Schmutz

Nottania K Campbell

Beda Joos

Maria Rita Lecca

Andrea Patrignani

Martin Daumer

Christian Beisel

Peter Rusert

Alexandra Trkola

Huldrych F Gunthard

Volker Roth

Niko Beerenwinkel

Karin J Metzner

Affiliations

Soon will be listed here.

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.

Citing Articles

Comparative Evaluation of Open-Source Bioinformatics Pipelines for Full-Length Viral Genome Assembly.

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VILOCA: sequencing quality-aware viral haplotype reconstruction and mutation calling for short-read and long-read data.

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Using viral diversity to identify HIV-1 variants under HLA-dependent selection in a systematic viral genome-wide screen.

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Self-reported neurocognitive complaints in the Swiss HIV Cohort Study: a viral genome-wide association study.

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