文章基本信息

标题：Using phylogenetics to infer HIV-1 transmission direction between known transmission pairs
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作者：Christian Julian Villabona-Arenas ; Stéphane Hué ; James A. C. Baxter 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：38
DOI：10.1073/pnas.2210604119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance Identifying the transmission direction between individuals provides unparalleled power to understand infectious disease epidemiology. With epidemiological and clinical information typically unavailable to infer transmission direction, phylogenetic analysis of pathogen sequence data offers an alternative approach. While the success of this phylogenetic analysis varies, the reasons remain unknown. We analyze sequence data from over 100 transmission pairs for which both the transmission direction of HIV is known and detailed additional information is available. We find that easily quantifiable phylogenetic and sampling characteristics discriminate whether a phylogenetically inferred transmission direction is correct. Our analysis highlights that while phylogenetic approaches to infer transmission direction are unsuitable for individual-level analysis, such as forensic investigations, confidence in source attribution can be incorporated in population-level analyses. Inferring the transmission direction between linked individuals living with HIV provides unparalleled power to understand the epidemiology that determines transmission. Phylogenetic ancestral-state reconstruction approaches infer the transmission direction by identifying the individual in whom the most recent common ancestor of the virus populations originated. While these methods vary in accuracy, it is unclear why. To evaluate the performance of phylogenetic ancestral-state reconstruction to determine the transmission direction of HIV-1 infection, we inferred the transmission direction for 112 transmission pairs where transmission direction and detailed additional information were available. We then fit a statistical model to evaluate the extent to which epidemiological, sampling, genetic, and phylogenetic factors influenced the outcome of the inference. Finally, we repeated the analysis under real-life conditions with only routinely available data. We found that whether ancestral-state reconstruction correctly infers the transmission direction depends principally on the phylogeny's topology. For example, under real-life conditions, the probability of identifying the correct transmission direction increases from 32%—when a monophyletic–monophyletic or paraphyletic–polyphyletic tree topology is observed and when the tip closest to the root does not agree with the state at the root—to 93% when a paraphyletic–monophyletic topology is observed and when the tip closest to the root agrees with the root state. Our results suggest that documenting larger differences in relative intrahost diversity increases our confidence in the transmission direction inference of linked pairs for population-level studies of HIV. These findings provide a practical starting point to determine our confidence in transmission direction inference from ancestral-state reconstruction.
关键词：enphylogenetic tree topologyLasso regressionancestral-state reconstructionHIV-1 epidemiologywho acquires infection from whom