New Benchmarking Shows Limited Generalization Power of TCR Antigenic Epitope Prediction Models

• URL: http://arxiv.org/abs/2606.04994v1
• Date: Wed, 03 Jun 2026 15:14:05 GMT
• Title: New Benchmarking Shows Limited Generalization Power of TCR Antigenic Epitope Prediction Models
• Abstract summary: Computational prediction of T cell receptor (TCR) antigen specificity would transform the study of T cell biology and enable scalable immune engineering.<n>Existing models lack sufficient sensitivity and specificity for broad applications.<n>Here, we describe two complementary classes of datasets that allow unbiased evaluation of model performance and generalizability.
• Score: 19.41265373735755
• License: http://arxiv.org/licenses/nonexclusive-distrib/1.0/
• Abstract: Accurate computational prediction of T cell receptor (TCR) antigen specificity would transform the study of T cell biology and enable scalable immune engineering, yet existing models lack sufficient sensitivity and specificity for broad applications. A major limitation is the absence of rigorously defined, unseen benchmark datasets that allow unbiased evaluation of model performance and generalizability. Here, we describe two complementary classes of datasets that meet this criterion and argue that they provide both a robust framework for model assessment and a foundation for next-generation TCR-antigen prediction algorithm development.

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