Learning patterns of HIV-1 resistance to broadly neutralizing antibodies with reduced subtype bias using multi-task learning

The ability to predict HIV-1 resistance to broadly neutralizing antibodies (bnAbs) will increase bnAb therapeutic benefits. Machine learning is a powerful approach for such prediction. One challenge is that some HIV-1 subtypes in currently available training datasets are underrepresented, which like...

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Main Authors: Igiraneza, AB, Zacharopoulou, P, Hinch, R, Wymant, C, Abeler-Dörner, L, Frater, J, Fraser, C
格式: Journal article
语言:English
出版: Public Library of Science 2024
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author Igiraneza, AB
Zacharopoulou, P
Hinch, R
Wymant, C
Abeler-Dörner, L
Frater, J
Fraser, C
author_facet Igiraneza, AB
Zacharopoulou, P
Hinch, R
Wymant, C
Abeler-Dörner, L
Frater, J
Fraser, C
author_sort Igiraneza, AB
collection OXFORD
description The ability to predict HIV-1 resistance to broadly neutralizing antibodies (bnAbs) will increase bnAb therapeutic benefits. Machine learning is a powerful approach for such prediction. One challenge is that some HIV-1 subtypes in currently available training datasets are underrepresented, which likely affects models’ generalizability across subtypes. A second challenge is that combinations of bnAbs are required to avoid the inevitable resistance to a single bnAb, and computationally determining optimal combinations of bnAbs is an unsolved problem. Recently, machine learning models trained using resistance outcomes for multiple antibodies at once, a strategy called multi-task learning (MTL), have been shown to improve predictions. We develop a new model and show that, beyond the boost in performance, MTL also helps address the previous two challenges. Specifically, we demonstrate empirically that MTL can mitigate bias from underrepresented subtypes, and that MTL allows the model to learn patterns of co-resistance to combinations of antibodies, thus providing tools to predict antibodies’ epitopes and to potentially select optimal bnAb combinations. Our analyses, publicly available at https://github.com/iaime/LBUM, can be adapted to other infectious diseases that are treated with antibody therapy.
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spelling oxford-uuid:91f133fa-b7e8-4b9e-8f24-adf616f8e0ab2024-12-04T20:09:36ZLearning patterns of HIV-1 resistance to broadly neutralizing antibodies with reduced subtype bias using multi-task learningJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:91f133fa-b7e8-4b9e-8f24-adf616f8e0abEnglishJisc Publications RouterPublic Library of Science2024Igiraneza, ABZacharopoulou, PHinch, RWymant, CAbeler-Dörner, LFrater, JFraser, CThe ability to predict HIV-1 resistance to broadly neutralizing antibodies (bnAbs) will increase bnAb therapeutic benefits. Machine learning is a powerful approach for such prediction. One challenge is that some HIV-1 subtypes in currently available training datasets are underrepresented, which likely affects models’ generalizability across subtypes. A second challenge is that combinations of bnAbs are required to avoid the inevitable resistance to a single bnAb, and computationally determining optimal combinations of bnAbs is an unsolved problem. Recently, machine learning models trained using resistance outcomes for multiple antibodies at once, a strategy called multi-task learning (MTL), have been shown to improve predictions. We develop a new model and show that, beyond the boost in performance, MTL also helps address the previous two challenges. Specifically, we demonstrate empirically that MTL can mitigate bias from underrepresented subtypes, and that MTL allows the model to learn patterns of co-resistance to combinations of antibodies, thus providing tools to predict antibodies’ epitopes and to potentially select optimal bnAb combinations. Our analyses, publicly available at https://github.com/iaime/LBUM, can be adapted to other infectious diseases that are treated with antibody therapy.
spellingShingle Igiraneza, AB
Zacharopoulou, P
Hinch, R
Wymant, C
Abeler-Dörner, L
Frater, J
Fraser, C
Learning patterns of HIV-1 resistance to broadly neutralizing antibodies with reduced subtype bias using multi-task learning
title Learning patterns of HIV-1 resistance to broadly neutralizing antibodies with reduced subtype bias using multi-task learning
title_full Learning patterns of HIV-1 resistance to broadly neutralizing antibodies with reduced subtype bias using multi-task learning
title_fullStr Learning patterns of HIV-1 resistance to broadly neutralizing antibodies with reduced subtype bias using multi-task learning
title_full_unstemmed Learning patterns of HIV-1 resistance to broadly neutralizing antibodies with reduced subtype bias using multi-task learning
title_short Learning patterns of HIV-1 resistance to broadly neutralizing antibodies with reduced subtype bias using multi-task learning
title_sort learning patterns of hiv 1 resistance to broadly neutralizing antibodies with reduced subtype bias using multi task learning
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