Phylogenetically resolving epidemiologic linkage
Phylogenetically resolving epidemiologic linkage
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DOI：
10.1073/pnas.1522930113
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发表时间：
2016-03-08
影响因子：
11.1
通讯作者：
Leitner, Thomas
中科院分区：
文献类型：
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作者：
Romero-Severson, Ethan O.;Bulla, Ingo;Leitner, Thomas
尽管系统发育树在流行病学调查中的使用已变得普遍，但其流行病学解释尚未得到系统评估。在这里，我们使用 HIV-1 宿主内合并模型来概率评估两个流行病学相关宿主的传播历史。先前对系统发育重建的批评声称，传播方向很难推断，并且永远不能排除未采样的中间环节或共同来源的存在。根据分支关系以及重建是否与真实的传播历史一致，流行病学相关宿主的HIV群体之间的系统发育关系可以分为六类树。我们表明，传播方向以及是否存在未抽样的中间联系或共同来源对预期的系统发育关系做出了截然不同的预测：（i）当并系存在时，通常可以确定传播方向；（ii）当多个谱系传播时，可以排除中间联系；（iii）当采样个体的艾滋病毒群体都是单系时，共同来源可能是起源。表明传播方向错误的不一致结果通常很少见。此外，预期的树形拓扑还取决于传播谱系的数量、样本大小、样本相对于传播的时间以及感染后多样性增加的速度。通常，每个受试者 20 个或更多序列会给出可靠的结果。我们通过对真实传播历史的分析证实了我们的理论评估，并讨论了我们的发现如何帮助解释系统发育结果。
Although the use of phylogenetic trees in epidemiological investigations has become commonplace, their epidemiological interpretation has not been systematically evaluated. Here, we use an HIV-1 within-host coalescent model to probabilistically evaluate transmission histories of two epidemiologically linked hosts. Previous critique of phylogenetic reconstruction has claimed that direction of transmission is difficult to infer, and that the existence of unsampled intermediary links or common sources can never be excluded. The phylogenetic relationship between the HIV populations of epidemiologically linked hosts can be classified into six types of trees, based on cladistic relationships and whether the reconstruction is consistent with the true transmission history or not. We show that the direction of transmission and whether unsampled intermediary links or common sources existed make very different predictions about expected phylogenetic relationships: (i) Direction of transmission can often be established when paraphyly exists, (ii) intermediary links can be excluded when multiple lineages were transmitted, and (iii) when the sampled individuals' HIV populations both are monophyletic a common source was likely the origin. Inconsistent results, suggesting the wrong transmission direction, were generally rare. In addition, the expected tree topology also depends on the number of transmitted lineages, the sample size, the time of the sample relative to transmission, and how fast the diversity increases after infection. Typically, 20 or more sequences per subject give robust results. We confirm our theoretical evaluations with analyses of real transmission histories and discuss how our findings should aid in interpreting phylogenetic results.