Inference of Transmission Network Structure from HIV Phylogenetic Trees.

Federica Giardina, Ethan Obie Romero-Severson, Jan Albert, Tom Britton, Thomas Leitner
Author Information
  1. Federica Giardina: Department of Mathematics, Stockholm University, Stockholm, Sweden. ORCID
  2. Ethan Obie Romero-Severson: Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America. ORCID
  3. Jan Albert: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden. ORCID
  4. Tom Britton: Department of Mathematics, Stockholm University, Stockholm, Sweden.
  5. Thomas Leitner: Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.

Abstract

Phylogenetic inference is an attractive means to reconstruct transmission histories and epidemics. However, there is not a perfect correspondence between transmission history and virus phylogeny. Both node height and topological differences may occur, depending on the interaction between within-host evolutionary dynamics and between-host transmission patterns. To investigate these interactions, we added a within-host evolutionary model in epidemiological simulations and examined if the resulting phylogeny could recover different types of contact networks. To further improve realism, we also introduced patient-specific differences in infectivity across disease stages, and on the epidemic level we considered incomplete sampling and the age of the epidemic. Second, we implemented an inference method based on approximate Bayesian computation (ABC) to discriminate among three well-studied network models and jointly estimate both network parameters and key epidemiological quantities such as the infection rate. Our ABC framework used both topological and distance-based tree statistics for comparison between simulated and observed trees. Overall, our simulations showed that a virus time-scaled phylogeny (genealogy) may be substantially different from the between-host transmission tree. This has important implications for the interpretation of what a phylogeny reveals about the underlying epidemic contact network. In particular, we found that while the within-host evolutionary process obscures the transmission tree, the diversification process and infectivity dynamics also add discriminatory power to differentiate between different types of contact networks. We also found that the possibility to differentiate contact networks depends on how far an epidemic has progressed, where distance-based tree statistics have more power early in an epidemic. Finally, we applied our ABC inference on two different outbreaks from the Swedish HIV-1 epidemic.

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Grants

  1. R01 AI087520/NIAID NIH HHS

MeSH Term

Bayes Theorem
Computational Biology
Computer Simulation
Disease Outbreaks
HIV Infections
HIV-1
Humans
Models, Biological
Phylogeny
Sweden

Word Cloud

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