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HIV coreceptor tropism determination and mutational pattern identification

In the early stages of infection, Human Immunodeficiency Virus Type 1 (HIV-1) generally selects CCR5 as the primary coreceptor for entering the host cell. As infection progresses, the virus evolves and may exhibit a coreceptor-switch to CXCR4. Accurate determination coreceptor usage and identificati...

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Autores principales: Shen, Hui-Shuang, Yin, Jason, Leng, Fei, Teng, Rui-Fang, Xu, Chao, Xia, Xia-Yu, Pan, Xian-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756667/
https://www.ncbi.nlm.nih.gov/pubmed/26883082
http://dx.doi.org/10.1038/srep21280
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author Shen, Hui-Shuang
Yin, Jason
Leng, Fei
Teng, Rui-Fang
Xu, Chao
Xia, Xia-Yu
Pan, Xian-Ming
author_facet Shen, Hui-Shuang
Yin, Jason
Leng, Fei
Teng, Rui-Fang
Xu, Chao
Xia, Xia-Yu
Pan, Xian-Ming
author_sort Shen, Hui-Shuang
collection PubMed
description In the early stages of infection, Human Immunodeficiency Virus Type 1 (HIV-1) generally selects CCR5 as the primary coreceptor for entering the host cell. As infection progresses, the virus evolves and may exhibit a coreceptor-switch to CXCR4. Accurate determination coreceptor usage and identification key mutational patterns associated tropism switch are essential for selection of appropriate therapies and understanding mechanism of coreceptor change. We developed a classifier composed of two coreceptor-specific weight matrices (CMs) based on a full-scale dataset. For this classifier, we found an AUC of 0.97, an accuracy of 95.21% and an MCC of 0.885 (sensitivity 92.92%; specificity 95.54%) in a ten-fold cross-validation, outperforming all other methods on an independent dataset (13% higher MCC value than geno2pheno and 15% higher MCC value than PSSM). A web server (http://spg.med.tsinghua.edu.cn/CM.html) based on our classifier was provided. Patterns of genetic mutations that occur along with coreceptor transitions were further identified based on the score of each sequence. Six pairs of one-AA mutational patterns and three pairs of two-AA mutational patterns were identified to associate with increasing propensity for X4 tropism. These mutational patterns offered new insights into the mechanism of coreceptor switch and aided in monitoring coreceptor switch.
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spelling pubmed-47566672016-02-25 HIV coreceptor tropism determination and mutational pattern identification Shen, Hui-Shuang Yin, Jason Leng, Fei Teng, Rui-Fang Xu, Chao Xia, Xia-Yu Pan, Xian-Ming Sci Rep Article In the early stages of infection, Human Immunodeficiency Virus Type 1 (HIV-1) generally selects CCR5 as the primary coreceptor for entering the host cell. As infection progresses, the virus evolves and may exhibit a coreceptor-switch to CXCR4. Accurate determination coreceptor usage and identification key mutational patterns associated tropism switch are essential for selection of appropriate therapies and understanding mechanism of coreceptor change. We developed a classifier composed of two coreceptor-specific weight matrices (CMs) based on a full-scale dataset. For this classifier, we found an AUC of 0.97, an accuracy of 95.21% and an MCC of 0.885 (sensitivity 92.92%; specificity 95.54%) in a ten-fold cross-validation, outperforming all other methods on an independent dataset (13% higher MCC value than geno2pheno and 15% higher MCC value than PSSM). A web server (http://spg.med.tsinghua.edu.cn/CM.html) based on our classifier was provided. Patterns of genetic mutations that occur along with coreceptor transitions were further identified based on the score of each sequence. Six pairs of one-AA mutational patterns and three pairs of two-AA mutational patterns were identified to associate with increasing propensity for X4 tropism. These mutational patterns offered new insights into the mechanism of coreceptor switch and aided in monitoring coreceptor switch. Nature Publishing Group 2016-02-17 /pmc/articles/PMC4756667/ /pubmed/26883082 http://dx.doi.org/10.1038/srep21280 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Shen, Hui-Shuang
Yin, Jason
Leng, Fei
Teng, Rui-Fang
Xu, Chao
Xia, Xia-Yu
Pan, Xian-Ming
HIV coreceptor tropism determination and mutational pattern identification
title HIV coreceptor tropism determination and mutational pattern identification
title_full HIV coreceptor tropism determination and mutational pattern identification
title_fullStr HIV coreceptor tropism determination and mutational pattern identification
title_full_unstemmed HIV coreceptor tropism determination and mutational pattern identification
title_short HIV coreceptor tropism determination and mutational pattern identification
title_sort hiv coreceptor tropism determination and mutational pattern identification
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756667/
https://www.ncbi.nlm.nih.gov/pubmed/26883082
http://dx.doi.org/10.1038/srep21280
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