HIV-1 quasispecies delineation by tag linkage deep sequencing

Nicholas C. Wu, Justin De La Cruz, Laith Q. Al-Mawsawi, C. Anders Olson, Hangfei Qi, Harding H. Luan, Nguyen Nguyen, Yushen Du, Shuai Le, Ting Ting Wu, Xinmin Li, Martha J. Lewis, Otto O. Yang, Ren Sun

Research output: Contribution to journalArticlepeer-review

Abstract

Trade-offs between throughput, read length, and error rates in high-throughput sequencing limit certain applications such as monitoring viral quasispecies. Here, we describe a molecular-based tag linkage method that allows assemblage of short sequence reads into long DNA fragments. It enables haplotype phasing with high accuracy and sensitivity to interrogate individual viral sequences in a quasispecies. This approach is demonstrated to deduce ∼2000 unique 1.3 kb viral sequences from HIV-1 quasispecies in vivo and after passaging ex vivo with a detection limit of ∼0.005% to ∼0.001%. Reproducibility of the method is validated quantitatively and qualitatively by a technical replicate. This approach can improve monitoring of the genetic architecture and evolution dynamics in any quasispecies population.

Original languageEnglish (US)
Article numbere97505
JournalPloS one
Volume9
Issue number5
DOIs
StatePublished - May 19 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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