Modeling HIV-1 drug resistance as episodic directional selection.

The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection...

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Autores principales:	Ben Murrell, Tulio de Oliveira, Chris Seebregts, Sergei L Kosakovsky Pond, Konrad Scheffler, Southern African Treatment and Resistance Network-SATuRN Consortium
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0250d2a864864594b00a00d55834bfdb
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spelling	oai:doaj.org-article:0250d2a864864594b00a00d55834bfdb2021-11-18T05:51:21ZModeling HIV-1 drug resistance as episodic directional selection.1553-734X1553-735810.1371/journal.pcbi.1002507https://doaj.org/article/0250d2a864864594b00a00d55834bfdb2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22589711/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.Ben MurrellTulio de OliveiraChris SeebregtsSergei L Kosakovsky PondKonrad SchefflerSouthern African Treatment and Resistance Network-SATuRN ConsortiumPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 5, p e1002507 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Ben Murrell Tulio de Oliveira Chris Seebregts Sergei L Kosakovsky Pond Konrad Scheffler Southern African Treatment and Resistance Network-SATuRN Consortium Modeling HIV-1 drug resistance as episodic directional selection.
description	The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.
format	article
author	Ben Murrell Tulio de Oliveira Chris Seebregts Sergei L Kosakovsky Pond Konrad Scheffler Southern African Treatment and Resistance Network-SATuRN Consortium
author_facet	Ben Murrell Tulio de Oliveira Chris Seebregts Sergei L Kosakovsky Pond Konrad Scheffler Southern African Treatment and Resistance Network-SATuRN Consortium
author_sort	Ben Murrell
title	Modeling HIV-1 drug resistance as episodic directional selection.
title_short	Modeling HIV-1 drug resistance as episodic directional selection.
title_full	Modeling HIV-1 drug resistance as episodic directional selection.
title_fullStr	Modeling HIV-1 drug resistance as episodic directional selection.
title_full_unstemmed	Modeling HIV-1 drug resistance as episodic directional selection.
title_sort	modeling hiv-1 drug resistance as episodic directional selection.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/0250d2a864864594b00a00d55834bfdb
work_keys_str_mv	AT benmurrell modelinghiv1drugresistanceasepisodicdirectionalselection AT tuliodeoliveira modelinghiv1drugresistanceasepisodicdirectionalselection AT chrisseebregts modelinghiv1drugresistanceasepisodicdirectionalselection AT sergeilkosakovskypond modelinghiv1drugresistanceasepisodicdirectionalselection AT konradscheffler modelinghiv1drugresistanceasepisodicdirectionalselection AT southernafricantreatmentandresistancenetworksaturnconsortium modelinghiv1drugresistanceasepisodicdirectionalselection
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Modeling HIV-1 drug resistance as episodic directional selection.

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