AbDiver: a tool to explore the natural antibody landscape to aid therapeutic design

Author:

Młokosiewicz Jakub1,Deszyński Piotr1,Wilman Wiktoria1,Jaszczyszyn Igor12,Ganesan Rajkumar3ORCID,Kovaltsuk Aleksandr4,Leem Jinwoo5ORCID,Galson Jacob D5,Krawczyk Konrad1ORCID

Affiliation:

1. NaturalAntibody , 71-064 Szczecin, Poland

2. Medical University of Warsaw , 02-091 Warsaw, Poland

3. Alector , South San Francisco, CA 94080, USA

4. LabGenius , SE16 4DG London, UK

5. Alchemab Therapeutics Ltd, N1C 4AX London , UK

Abstract

Abstract Motivation Rational design of therapeutic antibodies can be improved by harnessing the natural sequence diversity of these molecules. Our understanding of the diversity of antibodies has recently been greatly facilitated through the deposition of hundreds of millions of human antibody sequences in next-generation sequencing (NGS) repositories. Contrasting a query therapeutic antibody sequence to naturally observed diversity in similar antibody sequences from NGS can provide a mutational roadmap for antibody engineers designing biotherapeutics. Because of the sheer scale of the antibody NGS datasets, performing queries across them is computationally challenging. Results To facilitate harnessing antibody NGS data, we developed AbDiver (http://naturalantibody.com/abdiver), a free portal allowing users to compare their query sequences to those observed in the natural repertoires. AbDiver offers three antibody-specific use-cases: (i) compare a query antibody to positional variability statistics precomputed from multiple independent studies, (ii) retrieve close full variable sequence matches to a query antibody and (iii) retrieve CDR3 or clonotype matches to a query antibody. We applied our system to a set of 742 therapeutic antibodies, demonstrating that for each use-case our system can retrieve relevant results for most sequences. AbDiver facilitates the navigation of vast antibody mutation space for the purpose of rational therapeutic antibody design. Availability and implementation AbDiver is freely accessible at http://naturalantibody.com/abdiver. Supplementary information Supplementary data are available at Bioinformatics online.

Publisher

Oxford University Press (OUP)

Subject

Computational Mathematics,Computational Theory and Mathematics,Computer Science Applications,Molecular Biology,Biochemistry,Statistics and Probability

Reference13 articles.

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2. Human antibody immune responses are personalized by selective removal of MHC-II peptide epitopes;Gutiérrez-González,2021

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5. Looking for therapeutic antibodies in next-generation sequencing repositories;Krawczyk;MAbs,2019

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