PT  - JOURNAL ARTICLE
AU  - Ceder Dens
AU  - Wout Bittremieux
AU  - Fabio Affaticati
AU  - Kris Laukens
AU  - Pieter Meysman
TI  - Interpretable deep learning to uncover the molecular binding patterns determining TCR–epitope interactions
AID  - 10.1101/2022.05.02.490264
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.02.490264
4099  - http://biorxiv.org/content/early/2022/10/04/2022.05.02.490264.short
4100  - http://biorxiv.org/content/early/2022/10/04/2022.05.02.490264.full
AB  - The recognition of an epitope by a T-cell receptor (TCR) is crucial for eliminating pathogens and establishing immunological memory. Prediction of the binding of any TCR–epitope pair is still a challenging task, especially for novel epitopes, because the underlying patterns are largely unknown to domain experts and machine learning models. To achieve a deeper understanding of TCR–epitope interactions, we have used interpretable deep learning techniques to gain insights into the performance of TCR–epitope binding machine learning models. We demonstrate how interpretable AI techniques can be linked to the three-dimensional structure of molecules to offer novel insights into the factors that determine TCR affinity on a molecular level. Additionally, our results show the importance of using interpretability techniques to verify the predictions of machine learning models for challenging molecular biology problems where small hard-to-detect problems can accumulate to inaccurate results.Competing Interest StatementKL and PM hold shares in ImmuneWatch BV, an immunoinformatics company.