Ambiguous nucleotide calls from population-based sequencing of HIV-1 are a marker for viral diversity and the age of infection.
Ambiguous nucleotide calls from population-based sequencing of HIV-1 are a marker for viral diversity and the age of infection.
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DOI：
10.1093/cid/ciq164
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发表时间：
2011-02-15
期刊：
影响因子：
--
通讯作者：
Swiss HIV Cohort Study
中科院分区：
文献类型：
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作者：
Kouyos RD;von Wyl V;Yerly S;Böni J;Rieder P;Joos B;Taffé P;Shah C;Bürgisser P;Klimkait T;Weber R;Hirschel B;Cavassini M;Rauch A;Battegay M;Vernazza PL;Bernasconi E;Ledergerber B;Bonhoeffer S;Günthard HF;Swiss HIV Cohort Study
在人类免疫缺陷病毒1型（HIV-1）的批量测序中，模糊核苷酸调用的分数携带了关于病毒多样性和感染年龄的重要信息。特别地，> 0.5%的模糊核苷酸的分数提供了针对<1年前的最近感染事件的证据。背景感染人类免疫缺陷病毒（HIV）的个体自感染以来所经过的时间（感染年龄）是一个重要但通常知之甚少的数量。我们评估了从批量测序获得的模糊核苷酸的分数是否可以作为该参数的代表，如基因型耐药性测试所做的那样。方法.我们将感染年龄与抗逆转录病毒治疗（ART）开始前HIV-1部分pol序列中的模糊核苷酸分数相关联。分析了三组瑞士HIV队列研究参与者，根据贝叶斯反算（n = 3，307）、血清转换（n = 366）或原发性HIV感染诊断（n = 130）估计感染年龄。此外，我们还研究了124名患者，他们在ART初治时进行了纵向基因型耐药检测。结果我们发现，随着感染年龄的增长，模糊核苷酸的比例增加，在前8年内每年增加0.2%，但此后以下降的速度增加。我们表明，这种模式是一致的人口遗传模型的现实参数。最后，我们表明，在这个高度代表性的群体中，> 0.5%的模糊核苷酸的分数提供了有力的证据，反对最近的感染事件<1年前采样（阴性预测值，98.7%）。结论.这些发现表明，模糊核苷酸的分数是一个有用的标记感染的年龄。
The fraction of ambiguous nucleotide calls in bulk sequencing of human immunodeficiency virus type 1 (HIV-1) carries important information on viral diversity and the age of infection. In particular, a fraction of ambiguous nucleotides of >.5% provides evidence against a recent infection event <1 year ago. Background. The time passed since the infection of a human immunodeficiency virus (HIV)–infected individual (the age of infection) is an important but often only poorly known quantity. We assessed whether the fraction of ambiguous nucleotides obtained from bulk sequencing as done for genotypic resistance testing can serve as a proxy of this parameter. Methods. We correlated the age of infection and the fraction of ambiguous nucleotides in partial pol sequences of HIV-1 sampled before initiation of antiretroviral therapy (ART). Three groups of Swiss HIV Cohort Study participants were analyzed, for whom the age of infection was estimated on the basis of Bayesian back calculation (n = 3,307), seroconversion (n = 366), or diagnoses of primary HIV infection (n = 130). In addition, we studied 124 patients for whom longitudinal genotypic resistance testing was performed while they were still ART-naïve. Results. We found that the fraction of ambiguous nucleotides increased with the age of infection with a rate of .2% per year within the first 8 years but thereafter with a decreasing rate. We show that this pattern is consistent with population-genetic models for realistic parameters. Finally, we show that, in this highly representative population, a fraction of ambiguous nucleotides of >.5% provides strong evidence against a recent infection event <1 year prior to sampling (negative predictive value, 98.7%). Conclusions. These findings show that the fraction of ambiguous nucleotides is a useful marker for the age of infection.
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DOI：
10.1073/pnas.0804192105
发表时间：
2008-10-28
影响因子：
11.1
作者：
Joos, Beda;Fischer, Marek;Guenthard, Huldrych F.
通讯作者：
Guenthard, Huldrych F.
影响因子：
168.9
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Ledergerber, B;Egger, M;Weber, R
通讯作者：
Weber, R
影响因子：
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Von Wyl, Viktor;Yerly, Sabine;Guenthard, Huldrych F.
通讯作者：
Guenthard, Huldrych F.
DOI：
10.1073/pnas.0802203105
发表时间：
2008-05-27
影响因子：
11.1
作者：
Keele, Brandon F.;Giorgi, Elena E.;Shaw, George M.
通讯作者：
Shaw, George M.
影响因子：
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Shankarappa, R;Margolick, JB;Mullins, JI
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