A transfer-learning approach to predict antigen immunogenicity and T-cell receptor specificity

Author:

Bravi Barbara12ORCID,Di Gioacchino Andrea2ORCID,Fernandez-de-Cossio-Diaz Jorge2ORCID,Walczak Aleksandra M2ORCID,Mora Thierry2ORCID,Cocco Simona2ORCID,Monasson Rémi2ORCID

Affiliation:

1. Department of Mathematics, Imperial College London

2. Laboratoire de Physique de l’Ecole Normale Supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Université Paris-Cité

Abstract

Antigen immunogenicity and the specificity of binding of T-cell receptors to antigens are key properties underlying effective immune responses. Here we propose diffRBM, an approach based on transfer learning and Restricted Boltzmann Machines, to build sequence-based predictive models of these properties. DiffRBM is designed to learn the distinctive patterns in amino-acid composition that, on the one hand, underlie the antigen’s probability of triggering a response, and on the other hand the T-cell receptor’s ability to bind to a given antigen. We show that the patterns learnt by diffRBM allow us to predict putative contact sites of the antigen-receptor complex. We also discriminate immunogenic and non-immunogenic antigens, antigen-specific and generic receptors, reaching performances that compare favorably to existing sequence-based predictors of antigen immunogenicity and T-cell receptor specificity.

Funder

Agence Nationale de la Recherche

European Research Council

HORIZON EUROPE Marie Sklodowska-Curie Actions

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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