系统发育方法在 HPTN 052 队列中预测异性恋伴侣间 HIV 传播方向时存在不一致性。
Phylogenetic Methods Inconsistently Predict the Direction of HIV Transmission Among Heterosexual Pairs in the HPTN 052 Cohort.
机构信息
BioInfoExperts, Thibodaux, Louisiana.
Big Data Institute, University of Oxford, United Kingdom.
出版信息
J Infect Dis. 2019 Sep 26;220(9):1406-1413. doi: 10.1093/infdis/jiy734.
BACKGROUND
We evaluated use of phylogenetic methods to predict the direction of human immunodeficiency virus (HIV) transmission.
METHODS
For 33 pairs of HIV-infected patients (hereafter, "index patients") and their partners who acquired genetically linked HIV infection during the study, samples were collected from partners and index patients close to the time when the partner seroconverted (hereafter, "SC samples"); for 31 pairs, samples collected from the index patient at an earlier time point (hereafter, "early index samples") were also available. Phylogenies were inferred using env next-generation sequences (1 tree per pair/subtype). The direction of transmission (DoT) predicted from each tree was classified as correct or incorrect on the basis of which sequences (those from the index patient or the partner) were closest to the root. DoT was also assessed using maximum parsimony to infer ancestral node states for 100 bootstrap trees.
RESULTS
DoT was predicted correctly for both single-pair and subtype-specific trees in 22 pairs (67%) by using SC samples and in 23 pairs (74%) by using early index samples. DoT was predicted incorrectly for 4 pairs (15%) by using SC or early index samples. In the bootstrap analysis, DoT was predicted correctly for 18 pairs (55%) by using SC samples and for 24 pairs (73%) by using early index samples. DoT was predicted incorrectly for 7 pairs (21%) by using SC samples and for 4 pairs (13%) by using early index samples.
CONCLUSIONS
Phylogenetic methods based solely on the tree topology of HIV env sequences, particularly without consideration of phylogenetic uncertainty, may be insufficient for determining DoT.
背景
我们评估了使用系统发育方法预测人类免疫缺陷病毒（HIV）传播方向的效果。
方法
在这项研究中，对于 33 对 HIV 感染的患者（即“索引患者”）及其在研究期间感染遗传上相关 HIV 的伴侣，从伴侣和接近伴侣血清转换（seroconversion，SC）时间的索引患者处收集样本（以下称为“SC 样本”）；对于 31 对，还收集了索引患者在更早时间点采集的样本（以下称为“早期索引样本”）。使用 env 下一代序列推断系统发育树（每对/亚型 1 棵树）。根据哪些序列（来自索引患者或伴侣的序列）最接近根，从每个树推断的传播方向（DoT）被分类为正确或不正确。还使用最大简约法对 100 个引导树推断祖先节点状态来评估 DoT。
结果
使用 SC 样本可正确预测 22 对（67%）和使用早期索引样本可正确预测 23 对（74%）的单对和亚型特异性树的 DoT。使用 SC 或早期索引样本，有 4 对（15%）的 DoT 预测错误。在引导分析中，使用 SC 样本可正确预测 18 对（55%）和使用早期索引样本可正确预测 24 对（73%）的 DoT。使用 SC 样本，有 7 对（21%）的 DoT 预测错误，使用早期索引样本，有 4 对（13%）的 DoT 预测错误。
结论
仅基于 HIV env 序列系统发育树拓扑的方法，特别是不考虑系统发育不确定性，可能不足以确定 DoT。
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