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Article . 2024 . Peer-reviewed
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Assessing transmission attribution risk from simulated sequencing data in HIV molecular epidemiology

Authors: Nascimento, FF; Mehta, SR; Little, SJ; Volz, EM;

Assessing transmission attribution risk from simulated sequencing data in HIV molecular epidemiology

Abstract

Background: HIV molecular epidemiology (ME) is the analysis of sequence data together with individual-level clinical, demographic, and behavioral data to understand HIV epidemiology. The use of ME has raised concerns regarding identification of the putative source in direct transmission events. This could result in harm ranging from stigma to criminal prosecution in some jurisdictions. Here we assessed the risks of ME using simulated HIV genetic sequencing data. Methods: We simulated social networks of men-who-have-sex-with-men, calibrating the simulations to data from San Diego. We used these networks to simulate consensus and next-generation sequence (NGS) data to evaluate the risks of identifying direct transmissions using different HIV sequence lengths, and population sampling depths. To identify the source of transmissions, we calculated infector probability and used phyloscanner software for the analysis of consensus and NGS data, respectively. Results: Consensus sequence analyses showed that the risk of correctly inferring the source (direct transmission) within identified transmission pairs was very small and independent of sampling depth. Alternatively, NGS analyses showed that identification of the source of a transmission was very accurate, but only for 6.5% of inferred pairs. False positive transmissions were also observed, where one or more unobserved intermediaries were present when compared to the true network. Conclusion: Source attribution using consensus sequences rarely infers direct transmission pairs with high confidence but is still useful for population studies. In contrast, source attribution using NGS data was much more accurate in identifying direct transmission pairs, but for only a small percentage of transmission pairs analyzed.

Countries
United Kingdom, United States
Keywords

Male, Biomedical and clinical sciences, Epidemiology and Social, 610, HIV Infections, molecular epidemiology, Medical and Health Sciences, Sexual and Gender Minorities, Virology, 616, Health Sciences, Genetics, 2.2 Factors relating to the physical environment, Humans, Homosexuality, Male, Phylogeny, Probability, Molecular Epidemiology, Psychology and Cognitive Sciences, HIV, Health sciences, Homosexuality, Biological Sciences, phylogenetics, Infectious Diseases, Sexually Transmitted Infections, HIV/AIDS, next-generation sequencing, Generic health relevance, consensus sequences, Infection, source attribution

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average
Green
hybrid