A computational method for immune repertoire mining that identifies novel binders from different clonotypes, demonstrated by identifying anti-pertussis toxoid antibodies
Author(s)
Type
Journal Article
Abstract
Due to their shared genetic history, antibodies from the same clonotype often bind to the same epitope. This knowledge is used in immune repertoire mining, where known binders are used to search bulk sequencing repertoires to identify new binders. However, current computational methods cannot identify epitope convergence between antibodies from different clonotypes, limiting the sequence diversity of antigen-specific antibodies that can be identified. We describe how the antibody binding site, the paratope, can be used to cluster antibodies with common antigen reactivity from different clonotypes. Our method, paratyping, uses the predicted paratope to identify these novel cross clonotype matches. We experimentally validated our predictions on a pertussis toxoid dataset. Our results show that even the simplest abstraction of the antibody binding site, using only the length of the loops involved and predicted binding residues, is sufficient to group antigen-specific antibodies and provide additional information to conventional clonotype analysis.
Date Issued
2021
Date Acceptance
2020-12-22
Citation
mAbs, 2021, 13 (1)
ISSN
1942-0862
Publisher
Taylor & Francis Group
Journal / Book Title
mAbs
Volume
13
Issue
1
Copyright Statement
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000606894300001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
Antibody discovery
BCR-seq
BINDING SITES
BROAD
CELLS
computational
GENERATION
HIV-1-NEUTRALIZING ANTIBODIES
immune repertoire mining
IMMUNOGLOBULIN
Life Sciences & Biomedicine
Medicine, Research & Experimental
MONOCLONAL-ANTIBODIES
paired sequencing
paratope
pertussis
pertussis toxoid
PREDICTION
Research & Experimental Medicine
Science & Technology
SEQUENCE
TOOLKIT
transgenic mouse
Publication Status
Published
Article Number
1869406
Date Publish Online
2021-01-11