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Inferring Viral Transmission Time from Phylogenies for Known Transmission Pairs.
Emma E Goldberg1, Erik J Lundgren1, Ethan O Romero-Severson1
1Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.
Molecular Biology and Evolution
|December 27, 2023
Summary
We developed a Markov model to estimate human immunodeficiency virus (HIV) transmission times using genetic data. This method offers accurate and precise HIV transmission time estimates, aiding in understanding transmission dynamics.
Area of Science:
- Epidemiology
- Computational Biology
- Virology
Background:
- Estimating the timing of human immunodeficiency virus (HIV) transmission is crucial for understanding transmission dynamics and informing public health interventions.
- Phylogenetic analysis of viral genetic data offers a powerful tool for inferring transmission events when direct observation is not possible.
Purpose of the Study:
- To develop and evaluate a novel single-parameter Markov model for inferring HIV transmission times from phylogenetic data.
- To compare the performance of the proposed Markov model against existing methods for transmission time estimation.
Main Methods:
- Development of a single-parameter Markov model to infer transmission time from HIV phylogenies.
- Construction of phylogenies using multiple virus sequences from individuals within transmission pairs.
- Comparison of the Markov model's performance against tree-based logical intervals, parsimony-like rules, and coalescent models using simulations.
Main Results:
- The Markov time-slice model provided accurate and narrower estimates of transmission time compared to existing methods across various simulation scenarios.
- Identified specific conditions, such as late transmission post-source infection and delayed sampling post-transmission, that challenge accurate time inference by any method.
- Real-world application to HIV transmission pairs showed congruence with case investigation data, though phylogenetic time calibration introduced significant uncertainty.
Conclusions:
- The developed Markov model is a valuable tool for accurate HIV transmission time inference.
- Phylogenetic time calibration uncertainty is a major limitation in current transmission time estimation, more so than model inference itself.
- Further research is needed to develop methods that fully leverage phylogenetic topology and node times for improved transmission inference.
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