Accurate Prediction for Antibody Resistance of Clinical HIV-1 Isolates

<div><p>Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) have promising utility in prevention and treatment of HIV-1 infection, and several are currently undergoing clinical trials. Due to the high sequence diversity and mutation rate of HIV-1, vira...

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Main Author: Reda Rawi (391865) (author)
Other Authors: Raghvendra Mall (581171) (author), Chen-Hsiang Shen (1577383) (author), S. Katie Farney (6806957) (author), Andrea Shiakolas (18618385) (author), Jing Zhou (168494) (author), Halima Bensmail (10400) (author), Tae-Wook Chun (73430) (author), Nicole A. Doria-Rose (8026886) (author), Rebecca M. Lynch (11434669) (author), John R. Mascola (229761) (author), Peter D. Kwong (161423) (author), Gwo-Yu Chuang (758832) (author)
Published: 2019
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author Reda Rawi (391865)
author2 Raghvendra Mall (581171)
Chen-Hsiang Shen (1577383)
S. Katie Farney (6806957)
Andrea Shiakolas (18618385)
Jing Zhou (168494)
Halima Bensmail (10400)
Tae-Wook Chun (73430)
Nicole A. Doria-Rose (8026886)
Rebecca M. Lynch (11434669)
John R. Mascola (229761)
Peter D. Kwong (161423)
Gwo-Yu Chuang (758832)
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author_facet Reda Rawi (391865)
Raghvendra Mall (581171)
Chen-Hsiang Shen (1577383)
S. Katie Farney (6806957)
Andrea Shiakolas (18618385)
Jing Zhou (168494)
Halima Bensmail (10400)
Tae-Wook Chun (73430)
Nicole A. Doria-Rose (8026886)
Rebecca M. Lynch (11434669)
John R. Mascola (229761)
Peter D. Kwong (161423)
Gwo-Yu Chuang (758832)
author_role author
dc.creator.none.fl_str_mv Reda Rawi (391865)
Raghvendra Mall (581171)
Chen-Hsiang Shen (1577383)
S. Katie Farney (6806957)
Andrea Shiakolas (18618385)
Jing Zhou (168494)
Halima Bensmail (10400)
Tae-Wook Chun (73430)
Nicole A. Doria-Rose (8026886)
Rebecca M. Lynch (11434669)
John R. Mascola (229761)
Peter D. Kwong (161423)
Gwo-Yu Chuang (758832)
dc.date.none.fl_str_mv 2019-10-11T03:00:00Z
dc.identifier.none.fl_str_mv 10.1038/s41598-019-50635-w
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Accurate_Prediction_for_Antibody_Resistance_of_Clinical_HIV-1_Isolates/25907239
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Clinical sciences
Information and computing sciences
Machine learning
HIV-1
Envelope glycoprotein (Env)
Prevention
Treatment
Clinical trials
Viral isolates
Resistance
Machine learning
dc.title.none.fl_str_mv Accurate Prediction for Antibody Resistance of Clinical HIV-1 Isolates
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) have promising utility in prevention and treatment of HIV-1 infection, and several are currently undergoing clinical trials. Due to the high sequence diversity and mutation rate of HIV-1, viral isolates are often resistant to specific bNAbs. Currently, resistant isolates are commonly identified by time-consuming and expensive in vitro neutralization assays. Here, we report machine learning classifiers that accurately predict resistance of HIV-1 isolates to 33 bNAbs. Notably, our classifiers achieved an overall prediction accuracy of 96% for 212 clinical isolates from patients enrolled in four different clinical trials. Moreover, use of gradient boosting machine – a tree-based machine learning method – enabled us to identify critical features, which had high accordance with epitope residues that distinguished between antibody resistance and sensitivity. The availability of an in silico antibody resistance predictor should facilitate informed decisions of antibody usage and sequence-based monitoring of viral escape in clinical settings.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-019-50635-w" target="_blank">https://dx.doi.org/10.1038/s41598-019-50635-w</a></p>
eu_rights_str_mv openAccess
id Manara2_26d5d10c15d890b20bc576699aefbd71
identifier_str_mv 10.1038/s41598-019-50635-w
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25907239
publishDate 2019
repository.mail.fl_str_mv
repository.name.fl_str_mv
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rights_invalid_str_mv CC BY 4.0
spelling Accurate Prediction for Antibody Resistance of Clinical HIV-1 IsolatesReda Rawi (391865)Raghvendra Mall (581171)Chen-Hsiang Shen (1577383)S. Katie Farney (6806957)Andrea Shiakolas (18618385)Jing Zhou (168494)Halima Bensmail (10400)Tae-Wook Chun (73430)Nicole A. Doria-Rose (8026886)Rebecca M. Lynch (11434669)John R. Mascola (229761)Peter D. Kwong (161423)Gwo-Yu Chuang (758832)Biomedical and clinical sciencesClinical sciencesInformation and computing sciencesMachine learningHIV-1Envelope glycoprotein (Env)PreventionTreatmentClinical trialsViral isolatesResistanceMachine learning<div><p>Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) have promising utility in prevention and treatment of HIV-1 infection, and several are currently undergoing clinical trials. Due to the high sequence diversity and mutation rate of HIV-1, viral isolates are often resistant to specific bNAbs. Currently, resistant isolates are commonly identified by time-consuming and expensive in vitro neutralization assays. Here, we report machine learning classifiers that accurately predict resistance of HIV-1 isolates to 33 bNAbs. Notably, our classifiers achieved an overall prediction accuracy of 96% for 212 clinical isolates from patients enrolled in four different clinical trials. Moreover, use of gradient boosting machine – a tree-based machine learning method – enabled us to identify critical features, which had high accordance with epitope residues that distinguished between antibody resistance and sensitivity. The availability of an in silico antibody resistance predictor should facilitate informed decisions of antibody usage and sequence-based monitoring of viral escape in clinical settings.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-019-50635-w" target="_blank">https://dx.doi.org/10.1038/s41598-019-50635-w</a></p>2019-10-11T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41598-019-50635-whttps://figshare.com/articles/journal_contribution/Accurate_Prediction_for_Antibody_Resistance_of_Clinical_HIV-1_Isolates/25907239CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259072392019-10-11T03:00:00Z
spellingShingle Accurate Prediction for Antibody Resistance of Clinical HIV-1 Isolates
Reda Rawi (391865)
Biomedical and clinical sciences
Clinical sciences
Information and computing sciences
Machine learning
HIV-1
Envelope glycoprotein (Env)
Prevention
Treatment
Clinical trials
Viral isolates
Resistance
Machine learning
status_str publishedVersion
title Accurate Prediction for Antibody Resistance of Clinical HIV-1 Isolates
title_full Accurate Prediction for Antibody Resistance of Clinical HIV-1 Isolates
title_fullStr Accurate Prediction for Antibody Resistance of Clinical HIV-1 Isolates
title_full_unstemmed Accurate Prediction for Antibody Resistance of Clinical HIV-1 Isolates
title_short Accurate Prediction for Antibody Resistance of Clinical HIV-1 Isolates
title_sort Accurate Prediction for Antibody Resistance of Clinical HIV-1 Isolates
topic Biomedical and clinical sciences
Clinical sciences
Information and computing sciences
Machine learning
HIV-1
Envelope glycoprotein (Env)
Prevention
Treatment
Clinical trials
Viral isolates
Resistance
Machine learning