SPMM: estimating infection duration of multivariant HIV-1 infections

被引:12
作者
Love, Tanzy M. T. [1 ]
Park, Sung Yong [2 ]
Giorgi, Elena E. [3 ]
Mack, Wendy J. [4 ]
Perelson, Alan S. [3 ]
Lee, Ha Youn [2 ]
机构
[1] Univ Rochester, Dept Biostat & Computat Biol, 601 Elmwood Ave, Rochester, NY 14642 USA
[2] Univ So Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90089 USA
[3] Los Alamos Natl Lab, Theoret Biol & Biophys, POB 1663, Los Alamos, NM 87545 USA
[4] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA
关键词
IMMUNODEFICIENCY-VIRUS TYPE-1; INCIDENCE ASSAY; RECOMBINATION; DYNAMICS; ANTIBODY; VIREMIA; TRANSMISSION; POPULATION; VARIANTS; MULTIPLE;
D O I
10.1093/bioinformatics/btv749
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Motivation: Illustrating how HIV-1 is transmitted and how it evolves in the following weeks is an important step for developing effective vaccination and prevention strategies. It is currently possible through DNA sequencing to account for the diverse array of viral strains within an infected individual. This provides an unprecedented opportunity to pinpoint when each patient was infected and which viruses were transmitted. Results: Here we develop a mathematical tool for early HIV-1 evolution within a subject whose infection originates either from a single or multiple viral variants. The shifted Poisson mixture model (SPMM) provides a quantitative guideline for segregating viral lineages, which in turn enables us to assess when a subject was infected. The infection duration estimated by SPMM showed a statistically significant linear relationship with that by Fiebig laboratory staging (<P = 0.00059) among 37 acutely infected subjects. Our tool provides a functional approach to understanding early genetic diversity, one of the most important parameters for deciphering HIV-1 transmission and predicting the rate of disease progression.
引用
收藏
页码:1308 / 1315
页数:8
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