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Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST

Many HIV prevention strategies are currently under consideration where it is highly informative to know the study participants’ times of infection. These can be estimated using viral sequence data sampled early in infection. However, there are several scenarios that, if not addressed, can skew timin...

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Autores principales: Giorgi, Elena E., Li, Hui, Bhattacharya, Tanmoy, Shaw, George M., Korber, Bette
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157514/
https://www.ncbi.nlm.nih.gov/pubmed/32209678
http://dx.doi.org/10.1128/mBio.00324-20
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author Giorgi, Elena E.
Li, Hui
Bhattacharya, Tanmoy
Shaw, George M.
Korber, Bette
author_facet Giorgi, Elena E.
Li, Hui
Bhattacharya, Tanmoy
Shaw, George M.
Korber, Bette
author_sort Giorgi, Elena E.
collection PubMed
description Many HIV prevention strategies are currently under consideration where it is highly informative to know the study participants’ times of infection. These can be estimated using viral sequence data sampled early in infection. However, there are several scenarios that, if not addressed, can skew timing estimates. These include multiple transmitted/founder (TF) viruses, APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like)-mediated mutational enrichment, and recombination. Here, we suggest a pipeline to identify these problems and resolve the biases that they introduce. We then compare two modeling strategies to obtain timing estimates from sequence data. The first, Poisson Fitter (PF), is based on a Poisson model of random accumulation of mutations relative to the TF virus (or viruses) that established the infection. The second uses a coalescence-based phylogenetic strategy as implemented in BEAST. The comparison is based on timing predictions using plasma viral RNA (cDNA) sequence data from 28 simian-human immunodeficiency virus (SHIV)-infected animals for which the exact day of infection is known. In this particular setting, based on nucleotide sequences from samples obtained in early infection, the Poisson method yielded more accurate, more precise, and unbiased estimates for the time of infection than did the explored implementations of BEAST.
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spelling pubmed-71575142020-04-15 Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST Giorgi, Elena E. Li, Hui Bhattacharya, Tanmoy Shaw, George M. Korber, Bette mBio Research Article Many HIV prevention strategies are currently under consideration where it is highly informative to know the study participants’ times of infection. These can be estimated using viral sequence data sampled early in infection. However, there are several scenarios that, if not addressed, can skew timing estimates. These include multiple transmitted/founder (TF) viruses, APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like)-mediated mutational enrichment, and recombination. Here, we suggest a pipeline to identify these problems and resolve the biases that they introduce. We then compare two modeling strategies to obtain timing estimates from sequence data. The first, Poisson Fitter (PF), is based on a Poisson model of random accumulation of mutations relative to the TF virus (or viruses) that established the infection. The second uses a coalescence-based phylogenetic strategy as implemented in BEAST. The comparison is based on timing predictions using plasma viral RNA (cDNA) sequence data from 28 simian-human immunodeficiency virus (SHIV)-infected animals for which the exact day of infection is known. In this particular setting, based on nucleotide sequences from samples obtained in early infection, the Poisson method yielded more accurate, more precise, and unbiased estimates for the time of infection than did the explored implementations of BEAST. American Society for Microbiology 2020-03-24 /pmc/articles/PMC7157514/ /pubmed/32209678 http://dx.doi.org/10.1128/mBio.00324-20 Text en Copyright © 2020 Giorgi et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Giorgi, Elena E.
Li, Hui
Bhattacharya, Tanmoy
Shaw, George M.
Korber, Bette
Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST
title Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST
title_full Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST
title_fullStr Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST
title_full_unstemmed Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST
title_short Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST
title_sort estimating the timing of early simian-human immunodeficiency virus infections: a comparison between poisson fitter and beast
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157514/
https://www.ncbi.nlm.nih.gov/pubmed/32209678
http://dx.doi.org/10.1128/mBio.00324-20
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