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Highly Sensitive and Specific Detection of Rare Variants in Mixed Viral Populations from Massively Parallel Sequence Data

Author

Listed:
  • Alexander R Macalalad
  • Michael C Zody
  • Patrick Charlebois
  • Niall J Lennon
  • Ruchi M Newman
  • Christine M Malboeuf
  • Elizabeth M Ryan
  • Christian L Boutwell
  • Karen A Power
  • Doug E Brackney
  • Kendra N Pesko
  • Joshua Z Levin
  • Gregory D Ebel
  • Todd M Allen
  • Bruce W Birren
  • Matthew R Henn

Abstract

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 (

Suggested Citation

  • Alexander R Macalalad & Michael C Zody & Patrick Charlebois & Niall J Lennon & Ruchi M Newman & Christine M Malboeuf & Elizabeth M Ryan & Christian L Boutwell & Karen A Power & Doug E Brackney & Kendr, 2012. "Highly Sensitive and Specific Detection of Rare Variants in Mixed Viral Populations from Massively Parallel Sequence Data," PLOS Computational Biology, Public Library of Science, vol. 8(3), pages 1-10, March.
    • Handle: RePEc:plo:pcbi00:1002417
    DOI: 10.1371/journal.pcbi.1002417
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    References listed on IDEAS

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    1. Nicholas Eriksson & Lior Pachter & Yumi Mitsuya & Soo-Yon Rhee & Chunlin Wang & Baback Gharizadeh & Mostafa Ronaghi & Robert W Shafer & Niko Beerenwinkel, 2008. "Viral Population Estimation Using Pyrosequencing," PLOS Computational Biology, Public Library of Science, vol. 4(5), pages 1-13, May.
    2. David Altshuler & Victor J. Pollara & Chris R. Cowles & William J. Van Etten & Jennifer Baldwin & Lauren Linton & Eric S. Lander, 2000. "An SNP map of the human genome generated by reduced representation shotgun sequencing," Nature, Nature, vol. 407(6803), pages 513-516, September.
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