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Title: Phylogenetically resolving epidemiologic linkage

Abstract

The use of phylogenetic trees in epidemiological investigations has become commonplace, but 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 samplemore » relative to transmission, and how fast the diversity increases after infection. Typically, 20 or more sequences per subject give robust results. Moreover, we confirm our theoretical evaluations with analyses of real transmission histories and discuss how our findings should aid in interpreting phylogenetic results.« less

Authors:
 [1];  [1];  [1]
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  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1249052
Report Number(s):
LA-UR-15-29298
Journal ID: ISSN 0027-8424
Grant/Contract Number:
R01AI087520; BU 2685/4-1; AC52-06NA25396
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 113; Journal Issue: 10; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Romero-Severson, Ethan O., Bulla, Ingo, and Leitner, Thomas. Phylogenetically resolving epidemiologic linkage. United States: N. p., 2016. Web. doi:10.1073/pnas.1522930113.
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Romero-Severson, Ethan O., Bulla, Ingo, & Leitner, Thomas. Phylogenetically resolving epidemiologic linkage. United States. doi:10.1073/pnas.1522930113.
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Romero-Severson, Ethan O., Bulla, Ingo, and Leitner, Thomas. Mon . "Phylogenetically resolving epidemiologic linkage". United States. doi:10.1073/pnas.1522930113. https://www.osti.gov/servlets/purl/1249052.
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@article{osti_1249052,
title = {Phylogenetically resolving epidemiologic linkage},
author = {Romero-Severson, Ethan O. and Bulla, Ingo and Leitner, Thomas},
abstractNote = {The use of phylogenetic trees in epidemiological investigations has become commonplace, but 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. Moreover, we confirm our theoretical evaluations with analyses of real transmission histories and discuss how our findings should aid in interpreting phylogenetic results.},
doi = {10.1073/pnas.1522930113},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 10,
volume = 113,
place = {United States},
year = {Mon Feb 22 00:00:00 EST 2016},
month = {Mon Feb 22 00:00:00 EST 2016}
}
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Journal Article:
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DOI:  10.1073/pnas.1522930113
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