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Antibody complementarity determining region design using high-capacity machine learning

Liu, Ge and Zeng, Haoyang and Mueller, Jonas and Carter, Brandon and Wang, Ziheng and Schilz, Jonas and Horny, Geraldine and Birnbaum, Michael and Ewert, Stefan and Gifford, David (2020) Antibody complementarity determining region design using high-capacity machine learning. Bioinformatics (Oxford, England), 36 (7). pp. 2126-2133. ISSN 13674811

Abstract

MOTIVATION: The precise targeting of antibodies and other protein therapeutics is required for their proper function and the elimination of deleterious off-target effects. Often the molecular structure of a therapeutic target is unknown and randomized methods are used to design antibodies without a model that relates antibody sequence to desired properties. RESULTS: Here, we present Ens-Grad, a machine learning method that can design complementarity determining regions of human Immunoglobulin G antibodies with target affinities that are superior to candidates derived from phage display panning experiments. We also demonstrate that machine learning can improve target specificity by the modular composition of models from different experimental campaigns, enabling a new integrative approach to improving target specificity. Our results suggest a new path for the discovery of therapeutic molecules by demonstrating that predictive and differentiable models of antibody binding can be learned from high-throughput experimental data without the need for target structural data. AVAILABILITY AND IMPLEMENTATION: Sequencing data of the phage panning experiment are deposited at NIH's Sequence Read Archive (SRA) under the accession number SRP158510. We make our code available at https://github.com/gifford-lab/antibody-2019. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Item Type: Article
Date Deposited: 09 Jun 2020 00:45
Last Modified: 09 Jun 2020 00:45
URI: https://oak.novartis.com/id/eprint/41309

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