Using phylogenetics to infer HIV-1 transmission direction between known transmission pairs

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 m...

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Main Authors: Villabona-Arenas, CJ, Hué, S, Baxter, JAC, Hall, M, Lythgoe, KA, Bradley, J, Atkins, KE
Format: Journal article
Language:English
Published: National Academy of Sciences 2022
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author Villabona-Arenas, CJ
Hué, S
Baxter, JAC
Hall, M
Lythgoe, KA
Bradley, J
Atkins, KE
author_facet Villabona-Arenas, CJ
Hué, S
Baxter, JAC
Hall, M
Lythgoe, KA
Bradley, J
Atkins, KE
author_sort Villabona-Arenas, CJ
collection OXFORD
description 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.
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spelling oxford-uuid:e7c1a7c2-f047-4859-ad0e-e15000a91b6b2023-06-01T18:00:34ZUsing phylogenetics to infer HIV-1 transmission direction between known transmission pairsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e7c1a7c2-f047-4859-ad0e-e15000a91b6bEnglishSymplectic ElementsNational Academy of Sciences2022Villabona-Arenas, CJHué, SBaxter, JACHall, MLythgoe, KABradley, JAtkins, KEInferring 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.
spellingShingle Villabona-Arenas, CJ
Hué, S
Baxter, JAC
Hall, M
Lythgoe, KA
Bradley, J
Atkins, KE
Using phylogenetics to infer HIV-1 transmission direction between known transmission pairs
title Using phylogenetics to infer HIV-1 transmission direction between known transmission pairs
title_full Using phylogenetics to infer HIV-1 transmission direction between known transmission pairs
title_fullStr Using phylogenetics to infer HIV-1 transmission direction between known transmission pairs
title_full_unstemmed Using phylogenetics to infer HIV-1 transmission direction between known transmission pairs
title_short Using phylogenetics to infer HIV-1 transmission direction between known transmission pairs
title_sort using phylogenetics to infer hiv 1 transmission direction between known transmission pairs
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