RAIN: machine learning-based identification for HIV-1 bNAbs.
Details
Serval ID
serval:BIB_7E0011402784
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
RAIN: machine learning-based identification for HIV-1 bNAbs.
Journal
Nature communications
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
24/06/2024
Peer-reviewed
Oui
Volume
15
Number
1
Pages
5339
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
FNS: 310030_20467
Publication Status: epublish
FNS: 310030_20467
Abstract
Broadly neutralizing antibodies (bNAbs) are promising candidates for the treatment and prevention of HIV-1 infections. Despite their critical importance, automatic detection of HIV-1 bNAbs from immune repertoires is still lacking. Here, we develop a straightforward computational method for the Rapid Automatic Identification of bNAbs (RAIN) based on machine learning methods. In contrast to other approaches, which use one-hot encoding amino acid sequences or structural alignment for prediction, RAIN uses a combination of selected sequence-based features for the accurate prediction of HIV-1 bNAbs. We demonstrate the performance of our approach on non-biased, experimentally obtained and sequenced BCR repertoires from HIV-1 immune donors. RAIN processing leads to the successful identification of distinct HIV-1 bNAbs targeting the CD4-binding site of the envelope glycoprotein. In addition, we validate the identified bNAbs using an in vitro neutralization assay and we solve the structure of one of them in complex with the soluble native-like heterotrimeric envelope glycoprotein by single-particle cryo-electron microscopy (cryo-EM). Overall, we propose a method to facilitate and accelerate HIV-1 bNAbs discovery from non-selected immune repertoires.
Keywords
HIV-1/immunology, Humans, Machine Learning, HIV Antibodies/immunology, Cryoelectron Microscopy, Antibodies, Neutralizing/immunology, HIV Infections/virology, HIV Infections/immunology, CD4 Antigens/metabolism, CD4 Antigens/immunology, Amino Acid Sequence, HIV Envelope Protein gp120/immunology, HIV Envelope Protein gp120/chemistry
Pubmed
Web of science
Open Access
Yes
Funding(s)
Swiss National Science Foundation
Create date
25/06/2024 8:20
Last modification date
26/07/2024 6:02