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AbDiver – A tool to explore the natural antibody landscape to aid therapeutic design

Jakub Młokosiewicz, Piotr Deszyński, Wiktoria Wilman, Igor Jaszczyszyn, Rajkumar Ganesan, Aleksandr Kovaltsuk, Jinwoo Leem, Jacob Galson, Konrad Krawczyk
doi: https://doi.org/10.1101/2021.11.03.467080
Jakub Młokosiewicz
1NaturalAntibody
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Piotr Deszyński
1NaturalAntibody
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Wiktoria Wilman
1NaturalAntibody
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Igor Jaszczyszyn
1NaturalAntibody
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Rajkumar Ganesan
2Alector
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Aleksandr Kovaltsuk
3LabGenius
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Jinwoo Leem
4Alchemab
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Jacob Galson
4Alchemab
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Konrad Krawczyk
1NaturalAntibody
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  • For correspondence: konrad@naturalantibody.com
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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 road-map 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: 1) compare a query antibody to positional variability statistics precomputed from multiple independent studies 2) retrieve close full variable sequence matches to a query antibody and 3) 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 and engineering.

Availability AbDiver is freely accessible at http://naturalantibody.com/abdiver.

Competing Interest Statement

JM, PD, WW, IJ and KK are employees of NaturalAntibody, JL and JG are employees of Alchemab, RG is an employee of Alector, AK is an employee of LabGenius.

Footnotes

  • http://naturalantibody.com/abdiver

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted November 03, 2021.
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AbDiver – A tool to explore the natural antibody landscape to aid therapeutic design
Jakub Młokosiewicz, Piotr Deszyński, Wiktoria Wilman, Igor Jaszczyszyn, Rajkumar Ganesan, Aleksandr Kovaltsuk, Jinwoo Leem, Jacob Galson, Konrad Krawczyk
bioRxiv 2021.11.03.467080; doi: https://doi.org/10.1101/2021.11.03.467080
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AbDiver – A tool to explore the natural antibody landscape to aid therapeutic design
Jakub Młokosiewicz, Piotr Deszyński, Wiktoria Wilman, Igor Jaszczyszyn, Rajkumar Ganesan, Aleksandr Kovaltsuk, Jinwoo Leem, Jacob Galson, Konrad Krawczyk
bioRxiv 2021.11.03.467080; doi: https://doi.org/10.1101/2021.11.03.467080

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