Abstract
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 Statement
KL and PM hold shares in ImmuneWatch BV, an immunoinformatics company.
Footnotes
ceder.dens{at}uantwerpen.be, wbittremieux{at}health.ucsd.edu, fabio.affaticati{at}uantwerpen.be, kris.laukens{at}uantwerpen.be,
Comparison of the feature attributions and residue proximity is now done with the Pearson Correlation Coefficient. Al plots are updated accordingly.