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

Elife. 2023 Sep 8:12:e85126. doi: 10.7554/eLife.85126.

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.

Keywords: computational biology; human; immune response; immunogenicity; machine learning; systems biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids*
  • Cell Membrane
  • Learning*
  • Mitochondrial Membranes
  • T-Cell Antigen Receptor Specificity

Substances

  • Amino Acids

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.