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BMC Genomics DOI:10.1186/1471-2164-13-475

De novo assembly of highly diverse viral populations.

Publication TypeJournal Article
Year of Publication2012
AuthorsYang, X, Charlebois, P, Gnerre, S, Coole, MG, Lennon, NJ, Levin, JZ, Qu, J, Ryan, EM, Zody, MC, Henn, MR
JournalBMC Genomics
Volume13
Pages475
Date Published2012 Sep 13
ISSN1471-2164
KeywordsAlgorithms, Computational Biology, Genome, Viral, Software
Abstract

BACKGROUND: Extensive genetic diversity in viral populations within infected hosts and the divergence of variants from existing reference genomes impede the analysis of deep viral sequencing data. A de novo population consensus assembly is valuable both as a single linear representation of the population and as a backbone on which intra-host variants can be accurately mapped. The availability of consensus assemblies and robustly mapped variants are crucial to the genetic study of viral disease progression, transmission dynamics, and viral evolution. Existing de novo assembly techniques fail to robustly assemble ultra-deep sequence data from genetically heterogeneous populations such as viruses into full-length genomes due to the presence of extensive genetic variability, contaminants, and variable sequence coverage.

RESULTS: We present VICUNA, a de novo assembly algorithm suitable for generating consensus assemblies from genetically heterogeneous populations. We demonstrate its effectiveness on Dengue, Human Immunodeficiency and West Nile viral populations, representing a range of intra-host diversity. Compared to state-of-the-art assemblers designed for haploid or diploid systems, VICUNA recovers full-length consensus and captures insertion/deletion polymorphisms in diverse samples. Final assemblies maintain a high base calling accuracy. VICUNA program is publicly available at: http://www.broadinstitute.org/scientific-community/science/projects/vira... viral-genomics-analysis-software.

CONCLUSIONS: We developed VICUNA, a publicly available software tool, that enables consensus assembly of ultra-deep sequence derived from diverse viral populations. While VICUNA was developed for the analysis of viral populations, its application to other heterogeneous sequence data sets such as metagenomic or tumor cell population samples may prove beneficial in these fields of research.

URLhttp://www.biomedcentral.com/1471-2164/13/475
DOI10.1186/1471-2164-13-475
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/22974120?dopt=Abstract

Alternate JournalBMC Genomics
PubMed ID22974120
PubMed Central IDPMC3469330
Grant ListHHSN272200900018C / / PHS HHS / United States