eLife (Sep 2023)

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

  • Barbara Bravi,
  • Andrea Di Gioacchino,
  • Jorge Fernandez-de-Cossio-Diaz,
  • Aleksandra M Walczak,
  • Thierry Mora,
  • Simona Cocco,
  • Rémi Monasson

DOI
https://doi.org/10.7554/eLife.85126
Journal volume & issue
Vol. 12

Abstract

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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.

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