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PLoS Comput Biol DOI:10.1371/journal.pcbi.1002417

Highly sensitive and specific detection of rare variants in mixed viral populations from massively parallel sequence data.

Publication TypeJournal Article
Year of Publication2012
AuthorsMacalalad, AR, Zody, MC, Charlebois, P, Lennon, NJ, Newman, RM, Malboeuf, CM, Ryan, EM, Boutwell, CL, Power, KA, Brackney, DE, Pesko, KN, Levin, JZ, Ebel, GD, Allen, TM, Birren, BW, Henn, MR
JournalPLoS Comput Biol
Date Published2012
KeywordsAlgorithms, Base Sequence, DNA, Viral, Genetic Variation, Molecular Sequence Data, Mutation, Sensitivity and Specificity, Sequence Alignment, Sequence Analysis, DNA

Viruses diversify over time within hosts, often undercutting the effectiveness of host defenses and therapeutic interventions. To design successful vaccines and therapeutics, it is critical to better understand viral diversification, including comprehensively characterizing the genetic variants in viral intra-host populations and modeling changes from transmission through the course of infection. Massively parallel sequencing technologies can overcome the cost constraints of older sequencing methods and obtain the high sequence coverage needed to detect rare genetic variants ( 97% sensitivity and > 97% specificity on control read sets. On data derived from a patient after four years of HIV-1 infection, V-Phaser detected 2,015 variants across the -10 kb genome, including 603 rare variants (


Alternate JournalPLoS Comput. Biol.
PubMed ID22438797
PubMed Central IDPMC3305335
Grant ListP01 AI074415 / AI / NIAID NIH HHS / United States
HHSN272200900006C / AI / NIAID NIH HHS / United States
HHSN272200900006C / / PHS HHS / United States
T32 AI007538 / AI / NIAID NIH HHS / United States
HHSN27220090018C / / PHS HHS / United States
P01-AI074415 / AI / NIAID NIH HHS / United States