Remodeling Peptide-MHC-TCR Triad Binding as Sequence Fusion for Immunogenicity Prediction

Fuente: arXiv
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Hauptverfasser: Ma, Jiahao, Li, Hongzong, Huang, Jian-Dong, Hu, Ye-Fan, Chen, Yifan
Format: Preprint
Veröffentlicht: 2025
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author Ma, Jiahao
Li, Hongzong
Huang, Jian-Dong
Hu, Ye-Fan
Chen, Yifan
author_facet Ma, Jiahao
Li, Hongzong
Huang, Jian-Dong
Hu, Ye-Fan
Chen, Yifan
contents The complex nature of tripartite peptide-MHC-TCR interactions is a critical yet underexplored area in immunogenicity prediction. Traditional studies on TCR-antigen binding have not fully addressed the complex dependencies in triad binding. In this paper, we propose new modeling approaches for these tripartite interactions, utilizing sequence information from MHCs, peptides, and TCRs. Our methods adhere to native sequence forms and align with biological processes to enhance prediction accuracy. By incorporating representation learning techniques, we introduce a fusion mechanism to integrate the three sequences effectively. Empirical experiments show that our models outperform traditional methods, achieving a 2.8 to 13.3 percent improvement in prediction accuracy across existing benchmarks. We further validate our approach with extensive ablation studies, demonstrating the effectiveness of the proposed model components. The model implementation, code, and supplementary materials, including a manuscript with colored hyperlinks and a technical appendix for digital viewing, will be open-sourced upon publication.
format Preprint
id arxiv_https___arxiv_org_abs_2501_01768
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Remodeling Peptide-MHC-TCR Triad Binding as Sequence Fusion for Immunogenicity Prediction
Ma, Jiahao
Li, Hongzong
Huang, Jian-Dong
Hu, Ye-Fan
Chen, Yifan
Biomolecules
The complex nature of tripartite peptide-MHC-TCR interactions is a critical yet underexplored area in immunogenicity prediction. Traditional studies on TCR-antigen binding have not fully addressed the complex dependencies in triad binding. In this paper, we propose new modeling approaches for these tripartite interactions, utilizing sequence information from MHCs, peptides, and TCRs. Our methods adhere to native sequence forms and align with biological processes to enhance prediction accuracy. By incorporating representation learning techniques, we introduce a fusion mechanism to integrate the three sequences effectively. Empirical experiments show that our models outperform traditional methods, achieving a 2.8 to 13.3 percent improvement in prediction accuracy across existing benchmarks. We further validate our approach with extensive ablation studies, demonstrating the effectiveness of the proposed model components. The model implementation, code, and supplementary materials, including a manuscript with colored hyperlinks and a technical appendix for digital viewing, will be open-sourced upon publication.
title Remodeling Peptide-MHC-TCR Triad Binding as Sequence Fusion for Immunogenicity Prediction
topic Biomolecules
url https://arxiv.org/abs/2501.01768