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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]
  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:
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.
Romero-Severson, Ethan O., Bulla, Ingo, & Leitner, Thomas. Phylogenetically resolving epidemiologic linkage. United States. doi:10.1073/pnas.1522930113.
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.
@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 = {2016},
month = {2}
}

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Works referenced in this record:

Molecular Epidemiology of HIV Transmission in a Dental Practice
journal, May 1992


Florida dentist case: research affiliation and ethics
journal, February 1992


The Continuing Case of the Florida Dentist
journal, May 1992


Support for dental HIV transmission
journal, May 1994

  • Hillis, David M.; Huelsenbeck, John P.
  • Nature, Vol. 369, Issue 6475
  • DOI: 10.1038/369024a0

Phylogenetic Analyses Indicate an Atypical Nurse-to-Patient Transmission of Human Immunodeficiency Virus Type 1
journal, March 2000


Lack of HIV Transmission in the Practice of a Dentist with AIDS
journal, December 1994


Molecular Investigation of Human Immunodeficiency Virus (HIV) Infection in a Patient of an HIV-Infected Surgeon
journal, June 1993


Molecular Analysis of Human Immunodeficiency Virus Strains Associated with a Case of Criminal Transmission of the Virus
journal, September 2000

  • Birch, Christopher J.; McCaw, Rhonda F.; Bulach, Dieter M.
  • The Journal of Infectious Diseases, Vol. 182, Issue 3
  • DOI: 10.1086/315751

Comparison of Bayesian and Maximum-Likelihood Phylogenetic Approaches in Two Legal Cases Involving Accusations of Transmission of HIV
journal, August 2009

  • Kaye, Matthew; Chibo, Doris; Birch, Chris
  • AIDS Research and Human Retroviruses, Vol. 25, Issue 8
  • DOI: 10.1089/aid.2008.0306

Molecular testing of multiple HIV-1 transmissions in a criminal case
journal, January 2005


Human Immunodeficiency Virus Type 1 Infection after Sexual Abuse: Value of Nucleic Acid Sequence Analysis in Identifying the Offender
journal, October 2000

  • Banaschak, Sibylle; Werwein, Marianne; Brinkmann, Bernd
  • Clinical Infectious Diseases, Vol. 31, Issue 4
  • DOI: 10.1086/318152

Molecular evidence of HIV-1 transmission in a criminal case
journal, October 2002

  • Metzker, M. L.; Mindell, D. P.; Liu, X. -M.
  • Proceedings of the National Academy of Sciences, Vol. 99, Issue 22
  • DOI: 10.1073/pnas.222522599

Source identification in two criminal cases using phylogenetic analysis of HIV-1 DNA sequences
journal, November 2010

  • Scaduto, D. I.; Brown, J. M.; Haaland, W. C.
  • Proceedings of the National Academy of Sciences, Vol. 107, Issue 50
  • DOI: 10.1073/pnas.1015673107

HIV-1 Transmission during Early Infection in Men Who Have Sex with Men: A Phylodynamic Analysis
journal, December 2013


Episodic Sexual Transmission of HIV Revealed by Molecular Phylodynamics
journal, March 2008


Dynamics of Two Separate but Linked HIV-1 CRF01_AE Outbreaks among Injection Drug Users in Stockholm, Sweden, and Helsinki, Finland
journal, October 2010

  • Skar, H.; Axelsson, M.; Berggren, I.
  • Journal of Virology, Vol. 85, Issue 1
  • DOI: 10.1128/JVI.01413-10

Birth-death skyline plot reveals temporal changes of epidemic spread in HIV and hepatitis C virus (HCV)
journal, December 2012

  • Stadler, T.; Kuhnert, D.; Bonhoeffer, S.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 1
  • DOI: 10.1073/pnas.1207965110

Epidemic Dynamics Revealed in Dengue Evolution
journal, December 2009

  • Bennett, S. N.; Drummond, A. J.; Kapan, D. D.
  • Molecular Biology and Evolution, Vol. 27, Issue 4
  • DOI: 10.1093/molbev/msp285

Science in court: the myth of HIV fingerprinting
journal, February 2011


Guidelines for HIV in court cases
journal, May 2011


Accurate reconstruction of a known HIV-1 transmission history by phylogenetic tree analysis.
journal, October 1996

  • Leitner, T.; Escanilla, D.; Franzen, C.
  • Proceedings of the National Academy of Sciences, Vol. 93, Issue 20
  • DOI: 10.1073/pnas.93.20.10864

Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection
journal, June 2009

  • Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Keele, Brandon F.
  • The Journal of Experimental Medicine, Vol. 206, Issue 6
  • DOI: 10.1084/jem.20090378

Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection
journal, May 2008

  • Keele, B. F.; Giorgi, E. E.; Salazar-Gonzalez, J. F.
  • Proceedings of the National Academy of Sciences, Vol. 105, Issue 21
  • DOI: 10.1073/pnas.0802203105

Characterization of Human Immunodeficiency Virus Type 1 (HIV-1) Diversity and Tropism in 145 Patients With Primary HIV-1 Infection
journal, October 2011

  • Rieder, P.; Joos, B.; Scherrer, A. U.
  • Clinical Infectious Diseases, Vol. 53, Issue 12
  • DOI: 10.1093/cid/cir725

High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men
journal, May 2010


Timing and Order of Transmission Events Is Not Directly Reflected in a Pathogen Phylogeny
journal, May 2014

  • Romero-Severson, Ethan; Skar, Helena; Bulla, Ingo
  • Molecular Biology and Evolution, Vol. 31, Issue 9
  • DOI: 10.1093/molbev/msu179

Variation in HIV-1 set-point viral load: Epidemiological analysis and an evolutionary hypothesis
journal, October 2007

  • Fraser, C.; Hollingsworth, T. D.; Chapman, R.
  • Proceedings of the National Academy of Sciences, Vol. 104, Issue 44
  • DOI: 10.1073/pnas.0708559104

HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time
journal, March 1996


Dynamics of Total, Linear Nonintegrated, and Integrated HIV‐1 DNA In Vivo and In Vitro
journal, February 2008

  • Koelsch, Kersten K.; Liu, Lin; Haubrich, Richard
  • The Journal of Infectious Diseases, Vol. 197, Issue 3
  • DOI: 10.1086/525283

Analysis of HIV-1 env gene sequences reveals evidence for a low effective number in the viral population
journal, March 1997

  • Brown, A. J. L.
  • Proceedings of the National Academy of Sciences, Vol. 94, Issue 5
  • DOI: 10.1073/pnas.94.5.1862

Stochastic processes strongly influence HIV-1 evolution during suboptimal protease-inhibitor therapy
journal, November 1998

  • Nijhuis, M.; Boucher, C. A. B.; Schipper, P.
  • Proceedings of the National Academy of Sciences, Vol. 95, Issue 24
  • DOI: 10.1073/pnas.95.24.14441

Stochastic or deterministic: what is the effective population size of HIV-1?
journal, December 2006

  • Kouyos, Roger D.; Althaus, Christian L.; Bonhoeffer, Sebastian
  • Trends in Microbiology, Vol. 14, Issue 12
  • DOI: 10.1016/j.tim.2006.10.001

An Uncommon Case of HIV-1 Transmission Due to a Knife Fight
journal, February 2011

  • Kao, Cheng–Feng; Hsia, Kan–Tai; Chang, Sui–Yuan
  • AIDS Research and Human Retroviruses, Vol. 27, Issue 2
  • DOI: 10.1089/aid.2010.0044

Inflammatory Genital Infections Mitigate a Severe Genetic Bottleneck in Heterosexual Transmission of Subtype A and C HIV-1
journal, January 2009


The Genealogical Population Dynamics of HIV-1 in a Large Transmission Chain: Bridging within and among Host Evolutionary Rates
journal, April 2014


Viral Linkage in HIV-1 Seroconverters and Their Partners in an HIV-1 Prevention Clinical Trial
journal, March 2011


Reduced evolutionary rates in HIV-1 reveal extensive latency periods among replicating lineages
journal, October 2014


Untangling the influences of unmodeled evolutionary processes on phylogenetic signal in a forensically important HIV-1 transmission cluster
journal, June 2014

  • Doyle, Vinson P.; Andersen, John J.; Nelson, Bradley J.
  • Molecular Phylogenetics and Evolution, Vol. 75
  • DOI: 10.1016/j.ympev.2014.02.022

Convergent and divergent sequence evolution in the surface envelope glycoprotein of human immunodeficiency virus type 1 within a single infected patient.
journal, June 1992

  • Holmes, E. C.; Zhang, L. Q.; Simmonds, P.
  • Proceedings of the National Academy of Sciences, Vol. 89, Issue 11
  • DOI: 10.1073/pnas.89.11.4835

Recombination elevates the effective evolutionary rate and facilitates the establishment of HIV-1 infection in infants after mother-to-child transmission
journal, November 2015


Molecular Footprint of Drug-Selective Pressure in a Human Immunodeficiency Virus Transmission Chain
journal, August 2005


Recent developments in the MAFFT multiple sequence alignment program
journal, March 2008


PHYML Online--a web server for fast maximum likelihood-based phylogenetic inference
journal, July 2005

  • Guindon, S.; Lethiec, F.; Duroux, P.
  • Nucleic Acids Research, Vol. 33, Issue Web Server
  • DOI: 10.1093/nar/gki352

    Works referencing / citing this record:

    Inferring HIV-1 transmission networks and sources of epidemic spread in Africa with deep-sequence phylogenetic analysis
    journal, March 2019