Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data

Broadly neutralizing monoclonal antibodies effective against the majority of circulating isolates of HIV-1 have been isolated from a small number of infected individuals. Definition of the conformational epitopes on the HIV spike to which these antibodies bind is of great value in defining targets f...

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Main Authors: Ferguson, Andrew L., Falkowska, Emilia, Walker, Laura M., Seaman, Michael S., Burton, Dennis R., Chakraborty, Arup K
Other Authors: Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Format: Article
Language:en_US
Published: Public Library of Science 2014
Online Access:http://hdl.handle.net/1721.1/86010
https://orcid.org/0000-0003-1268-9602
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author Ferguson, Andrew L.
Falkowska, Emilia
Walker, Laura M.
Seaman, Michael S.
Burton, Dennis R.
Chakraborty, Arup K
author2 Massachusetts Institute of Technology. Institute for Medical Engineering & Science
author_facet Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Ferguson, Andrew L.
Falkowska, Emilia
Walker, Laura M.
Seaman, Michael S.
Burton, Dennis R.
Chakraborty, Arup K
author_sort Ferguson, Andrew L.
collection MIT
description Broadly neutralizing monoclonal antibodies effective against the majority of circulating isolates of HIV-1 have been isolated from a small number of infected individuals. Definition of the conformational epitopes on the HIV spike to which these antibodies bind is of great value in defining targets for vaccine and drug design. Drawing on techniques from compressed sensing and information theory, we developed a computational methodology to predict key residues constituting the conformational epitopes on the viral spike from cross-clade neutralization activity data. Our approach does not require the availability of structural information for either the antibody or antigen. Predictions of the conformational epitopes of ten broadly neutralizing HIV-1 antibodies are shown to be in good agreement with new and existing experimental data. Our findings suggest that our approach offers a means to accelerate epitope identification for diverse pathogenic antigens.
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spelling mit-1721.1/860102022-09-30T22:00:26Z Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data Ferguson, Andrew L. Falkowska, Emilia Walker, Laura M. Seaman, Michael S. Burton, Dennis R. Chakraborty, Arup K Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Department of Physics Ragon Institute of MGH, MIT and Harvard Chakraborty, Arup K. Broadly neutralizing monoclonal antibodies effective against the majority of circulating isolates of HIV-1 have been isolated from a small number of infected individuals. Definition of the conformational epitopes on the HIV spike to which these antibodies bind is of great value in defining targets for vaccine and drug design. Drawing on techniques from compressed sensing and information theory, we developed a computational methodology to predict key residues constituting the conformational epitopes on the viral spike from cross-clade neutralization activity data. Our approach does not require the availability of structural information for either the antibody or antigen. Predictions of the conformational epitopes of ten broadly neutralizing HIV-1 antibodies are shown to be in good agreement with new and existing experimental data. Our findings suggest that our approach offers a means to accelerate epitope identification for diverse pathogenic antigens. Massachusetts Institute of Technology. Ragon Institute of MGH, MIT and Harvard National Institutes of Health (U.S.) (Director's Pioneer Award) 2014-04-03T19:49:37Z 2014-04-03T19:49:37Z 2013-12 2013-06 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/86010 Ferguson, Andrew L., Emilia Falkowska, Laura M. Walker, Michael S. Seaman, Dennis R. Burton, and Arup K. Chakraborty. “Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data.” Edited by Freddie Salsbury. PLoS ONE 8, no. 12 (December 2, 2013): e80562. https://orcid.org/0000-0003-1268-9602 en_US http://dx.doi.org/10.1371/journal.pone.0080562 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science PLoS
spellingShingle Ferguson, Andrew L.
Falkowska, Emilia
Walker, Laura M.
Seaman, Michael S.
Burton, Dennis R.
Chakraborty, Arup K
Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data
title Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data
title_full Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data
title_fullStr Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data
title_full_unstemmed Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data
title_short Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data
title_sort computational prediction of broadly neutralizing hiv 1 antibody epitopes from neutralization activity data
url http://hdl.handle.net/1721.1/86010
https://orcid.org/0000-0003-1268-9602
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