Abstract:IntroductionT-cell receptor (TCR) recognition of foreign peptides presented by the major histocompatibility complex (MHC) initiates the adaptive immune response against pathogens. While a large number of TCR sequences specific to different antigenic peptides are known to date, the structural data describing the conformation and contacting residues for TCR-peptide-MHC complexes is relatively limited. In the present study we aim to extend and analyze the set of available structures by performing highly accurate … Show more
“…Given the difficulty to predict the structure and binding interface of pMHC-TCR pairs, predicting their binding affinity from general rules of protein interactions remains a promising but arduous approach [5, 6]. Recent experimental advances [7, 8] have allowed for the generation of an increasing amount of data linking TCR sequences to peptide-MHC (pMHC) complexes, providing a large number of binding pairs.…”
The accurate prediction of binding between T-cell receptors (TCR) and their cognate epitopes is key to understanding the adaptive immune response and developing immunotherapies. Current methods face two significant limitations: the shortage of comprehensive high-quality data and the bias introduced by the selection of the negative training data commonly used in the supervised learning approaches. We propose a novel method, TULIP, that addresses both limitations by leveraging incomplete data and unsupervised learning and using the transformer architecture of language models. Our model is flexible and integrates all possible data sources, regardless of their quality or completeness. We demonstrate the existence of a bias introduced by the sampling procedure used in previous supervised approaches, emphasizing the need for an unsupervised approach. TULIP recognizes the specific TCRs binding an epitope, performing well on unseen epitopes. Our model outperforms state-of-the-art models and offers a promising direction for the development of more accurate TCR epitope recognition models.
“…Given the difficulty to predict the structure and binding interface of pMHC-TCR pairs, predicting their binding affinity from general rules of protein interactions remains a promising but arduous approach [5, 6]. Recent experimental advances [7, 8] have allowed for the generation of an increasing amount of data linking TCR sequences to peptide-MHC (pMHC) complexes, providing a large number of binding pairs.…”
The accurate prediction of binding between T-cell receptors (TCR) and their cognate epitopes is key to understanding the adaptive immune response and developing immunotherapies. Current methods face two significant limitations: the shortage of comprehensive high-quality data and the bias introduced by the selection of the negative training data commonly used in the supervised learning approaches. We propose a novel method, TULIP, that addresses both limitations by leveraging incomplete data and unsupervised learning and using the transformer architecture of language models. Our model is flexible and integrates all possible data sources, regardless of their quality or completeness. We demonstrate the existence of a bias introduced by the sampling procedure used in previous supervised approaches, emphasizing the need for an unsupervised approach. TULIP recognizes the specific TCRs binding an epitope, performing well on unseen epitopes. Our model outperforms state-of-the-art models and offers a promising direction for the development of more accurate TCR epitope recognition models.
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