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In Silico Analysis of Hepatitis B Virus Occult Associated Mutations in Botswana Using a Novel Algorithm

Occult hepatitis B infections (OBI) represent a reservoir of undiagnosed and untreated hepatitis B virus (HBV), hence the need to identify mutations that lead to this phenotype. Functionally characterizing these mutations by in vitro studies is time-consuming and expensive. To bridge this gap, in si...

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Autores principales: Anderson, Motswedi, Choga, Wonderful T., Moyo, Sikhulile, Bell, Trevor Graham, Mbangiwa, Tshepiso, Phinius, Bonolo B., Bhebhe, Lynette, Sebunya, Theresa K., Makhema, Joseph, Marlink, Richard, Kramvis, Anna, Essex, Max, Musonda, Rosemary M., Blackard, Jason T., Gaseitsiwe, Simani
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162659/
https://www.ncbi.nlm.nih.gov/pubmed/30134551
http://dx.doi.org/10.3390/genes9090420
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author Anderson, Motswedi
Choga, Wonderful T.
Moyo, Sikhulile
Bell, Trevor Graham
Mbangiwa, Tshepiso
Phinius, Bonolo B.
Bhebhe, Lynette
Sebunya, Theresa K.
Makhema, Joseph
Marlink, Richard
Kramvis, Anna
Essex, Max
Musonda, Rosemary M.
Blackard, Jason T.
Gaseitsiwe, Simani
author_facet Anderson, Motswedi
Choga, Wonderful T.
Moyo, Sikhulile
Bell, Trevor Graham
Mbangiwa, Tshepiso
Phinius, Bonolo B.
Bhebhe, Lynette
Sebunya, Theresa K.
Makhema, Joseph
Marlink, Richard
Kramvis, Anna
Essex, Max
Musonda, Rosemary M.
Blackard, Jason T.
Gaseitsiwe, Simani
author_sort Anderson, Motswedi
collection PubMed
description Occult hepatitis B infections (OBI) represent a reservoir of undiagnosed and untreated hepatitis B virus (HBV), hence the need to identify mutations that lead to this phenotype. Functionally characterizing these mutations by in vitro studies is time-consuming and expensive. To bridge this gap, in silico approaches, which predict the effect of amino acid (aa) variants on HBV protein function, are necessary. We developed an algorithm for determining the relevance of OBI-associated mutations using in silico approaches. A 3 kb fragment of subgenotypes A1 and D3 from 24 chronic HBV-infected (CHB) and 24 OBI participants was analyzed. To develop and validate the algorithm, the effects of 68 previously characterized occult-associated mutations were determined using three computational tools: PolyPhen2, SNAP2, and PROVEAN. The percentage of deleterious mutations (with impact on protein function) predicted were 52 (76.5%) by PolyPhen2, 55 (80.9%) by SNAP2, and 65 (95.6%) by PROVEAN. At least two tools correctly predicted 59 (86.8%) mutations as deleterious. To identify OBI-associated mutations exclusive to Botswana, study sequences were compared to CHB sequences from GenBank. Of the 43 OBI-associated mutations identified, 26 (60.5%) were predicted by at least two tools to have an impact on protein function. To our knowledge, this is the first study to use in silico approaches to determine the impact of OBI-associated mutations, thereby identifying potential candidates for functional analysis to facilitate mechanistic studies of the OBI phenotype.
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spelling pubmed-61626592018-10-10 In Silico Analysis of Hepatitis B Virus Occult Associated Mutations in Botswana Using a Novel Algorithm Anderson, Motswedi Choga, Wonderful T. Moyo, Sikhulile Bell, Trevor Graham Mbangiwa, Tshepiso Phinius, Bonolo B. Bhebhe, Lynette Sebunya, Theresa K. Makhema, Joseph Marlink, Richard Kramvis, Anna Essex, Max Musonda, Rosemary M. Blackard, Jason T. Gaseitsiwe, Simani Genes (Basel) Article Occult hepatitis B infections (OBI) represent a reservoir of undiagnosed and untreated hepatitis B virus (HBV), hence the need to identify mutations that lead to this phenotype. Functionally characterizing these mutations by in vitro studies is time-consuming and expensive. To bridge this gap, in silico approaches, which predict the effect of amino acid (aa) variants on HBV protein function, are necessary. We developed an algorithm for determining the relevance of OBI-associated mutations using in silico approaches. A 3 kb fragment of subgenotypes A1 and D3 from 24 chronic HBV-infected (CHB) and 24 OBI participants was analyzed. To develop and validate the algorithm, the effects of 68 previously characterized occult-associated mutations were determined using three computational tools: PolyPhen2, SNAP2, and PROVEAN. The percentage of deleterious mutations (with impact on protein function) predicted were 52 (76.5%) by PolyPhen2, 55 (80.9%) by SNAP2, and 65 (95.6%) by PROVEAN. At least two tools correctly predicted 59 (86.8%) mutations as deleterious. To identify OBI-associated mutations exclusive to Botswana, study sequences were compared to CHB sequences from GenBank. Of the 43 OBI-associated mutations identified, 26 (60.5%) were predicted by at least two tools to have an impact on protein function. To our knowledge, this is the first study to use in silico approaches to determine the impact of OBI-associated mutations, thereby identifying potential candidates for functional analysis to facilitate mechanistic studies of the OBI phenotype. MDPI 2018-08-21 /pmc/articles/PMC6162659/ /pubmed/30134551 http://dx.doi.org/10.3390/genes9090420 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Anderson, Motswedi
Choga, Wonderful T.
Moyo, Sikhulile
Bell, Trevor Graham
Mbangiwa, Tshepiso
Phinius, Bonolo B.
Bhebhe, Lynette
Sebunya, Theresa K.
Makhema, Joseph
Marlink, Richard
Kramvis, Anna
Essex, Max
Musonda, Rosemary M.
Blackard, Jason T.
Gaseitsiwe, Simani
In Silico Analysis of Hepatitis B Virus Occult Associated Mutations in Botswana Using a Novel Algorithm
title In Silico Analysis of Hepatitis B Virus Occult Associated Mutations in Botswana Using a Novel Algorithm
title_full In Silico Analysis of Hepatitis B Virus Occult Associated Mutations in Botswana Using a Novel Algorithm
title_fullStr In Silico Analysis of Hepatitis B Virus Occult Associated Mutations in Botswana Using a Novel Algorithm
title_full_unstemmed In Silico Analysis of Hepatitis B Virus Occult Associated Mutations in Botswana Using a Novel Algorithm
title_short In Silico Analysis of Hepatitis B Virus Occult Associated Mutations in Botswana Using a Novel Algorithm
title_sort in silico analysis of hepatitis b virus occult associated mutations in botswana using a novel algorithm
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162659/
https://www.ncbi.nlm.nih.gov/pubmed/30134551
http://dx.doi.org/10.3390/genes9090420
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