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T cell receptor (TCR) recognition of peptide-MHC (pMHC) complexes is fundamental to adaptive immunity and central to the development of T cell-based immunotherapies. While transformer-based models have shown promise in predicting TCR-pMHC…

Computational Engineering, Finance, and Science · Computer Science 2025-09-23 Jiarui Li , Zixiang Yin , Zhengming Ding , Samuel J. Landry , Ramgopal R. Mettu

Understanding the binding specificity between T-cell receptors (TCRs) and peptide-major histocompatibility complexes (pMHCs) is central to immunotherapy and vaccine development. However, current predictive models struggle with…

Quantitative Methods · Quantitative Biology 2025-12-29 Cong Qi , Hanzhang Fang , Siqi jiang , Tianxing Hu , Zhi Wei

Recent advancements in immune sequencing and experimental techniques are generating extensive T cell receptor (TCR) repertoire data, enabling the development of models to predict TCR binding specificity. Despite the computational challenges…

Quantitative Methods · Quantitative Biology 2024-07-24 Anna Weber , Aurélien Pélissier , María Rodríguez Martínez

T-cells play a key role in adaptive immunity by mounting specific responses against diverse pathogens. An effective binding between T-cell receptors (TCRs) and pathogen-derived peptides presented on Major Histocompatibility Complexes (MHCs)…

Quantitative Methods · Quantitative Biology 2025-09-05 Gian Marco Visani , Michael N. Pun , Anastasia A. Minervina , Philip Bradley , Paul Thomas , Armita Nourmohammad

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.…

Biomolecules · Quantitative Biology 2025-01-06 Jiahao Ma , Hongzong Li , Jian-Dong Huang , Ye-Fan Hu , Yifan Chen

The anti-cancer immune response relies on the bindings between T-cell receptors (TCRs) and antigens, which elicits adaptive immunity to eliminate tumor cells. This ability of the immune system to respond to novel various neoantigens arises…

Quantitative Methods · Quantitative Biology 2025-11-11 Xing Fang , Chenpeng Yu , Shiye Tian , Hui Liu

CD8+ "killer" T cells and CD4+ "helper" T cells play a central role in the adaptive immune system by recognizing antigens presented by Major Histocompatibility Complex (pMHC) molecules via T Cell Receptors (TCRs). Modeling binding between T…

Computational Engineering, Finance, and Science · Computer Science 2026-03-09 Jiarui Li , Zixiang Yin , Haley Smith , Zhengming Ding , Samuel J. Landry , Ramgopal R. Mettu

T cells are a critical component of the adaptive immune system, playing a role in infectious disease, autoimmunity, and cancer. T cell function is mediated by the T cell receptor (TCR) protein, a highly diverse receptor targeting specific…

Machine Learning · Computer Science 2026-03-31 Marco Garcia Noceda , Matthew T Noakes , Andrew FigPope , Daniel E Mattox , Bryan Howie , Harlan Robins

The T cell arm of the adaptive immune system provides the host protection against unknown pathogens by discriminating between host and foreign material. This discriminatory capability is achieved by the creation of a repertoire of cells…

Biological Physics · Physics 2022-01-03 Kevin Ng Chau , Jason T. George , José N. Onuchic , Xingcheng Lin , Herbert Levine

It has been verified that only a small fraction of the neoantigens presented by MHC class I molecules on the cell surface can elicit T cells. The limitation can be attributed to the binding specificity of T cell receptor (TCR) to…

Quantitative Methods · Quantitative Biology 2022-06-24 Yiming Fang , Xuejun Liu , Hui Liu

T cells monitor the health status of cells by identifying foreign peptides displayed on their surface. T-cell receptors (TCRs), which are protein complexes found on the surface of T cells, are able to bind to these peptides. This process is…

Quantitative Methods · Quantitative Biology 2023-03-07 Ziqi Chen , Martin Renqiang Min , Hongyu Guo , Chao Cheng , Trevor Clancy , Xia Ning

Predicting T-cell receptor (TCR)--peptide-MHC (pMHC) binding is central to vaccine design and T-cell therapy, yet deployed models frequently encounter epitopes unseen during training, causing silent overconfidence and unreliable…

Graphics · Computer Science 2026-04-16 Arman Bekov , Timur Bekzhanov , Bekzat Sadykov

T-cell receptors (TCR) are key proteins of the adaptive immune system, generated randomly in each individual, whose diversity underlies our ability to recognize infections and malignancies. Modeling the distribution of TCR sequences is of…

Quantitative Methods · Quantitative Biology 2020-07-01 Giulio Isacchini , Zachary Sethna , Yuval Elhanati , Armita Nourmohammad , Aleksandra M. Walczak , Thierry Mora

The interpretability of model has become one of the obstacles to its wide application in the high-stake fields. The usual way to obtain interpretability is to build a black-box first and then explain it using the post-hoc methods. However,…

Machine Learning · Computer Science 2023-04-04 Zihao Chen , Xiaomeng Wang , Yuanjiang Huang , Tao Jia

In cancer therapeutics, protein-metal binding mechanisms critically govern the pharmacokinetics and targeting efficacy of drugs, thereby fundamentally shaping the rational design of anticancer metallodrugs. While conventional laboratory…

T-cell receptors can recognize foreign peptides bound to major histocompatibility complex (MHC) class-I proteins, and thus trigger the adaptive immune response. Therefore, identifying peptides that can bind to MHC class-I molecules plays a…

Quantitative Methods · Quantitative Biology 2020-12-09 Ziqi Chen , Martin Renqiang Min , Xia Ning

Recommendation Systems have become integral to modern user experiences, but lack transparency in their decision-making processes. Existing explainable recommendation methods are hindered by reliance on a post-hoc paradigm, wherein…

Information Retrieval · Computer Science 2024-12-04 Xiaohan Yu , Li Zhang , Chong Chen

Graph Neural Networks have been widely applied in critical decision-making areas that demand interpretable predictions, leading to the flourishing development of interpretability algorithms. However, current graph interpretability…

Machine Learning · Computer Science 2024-09-04 Xiaodi Li , Jianfeng Gui , Qian Gao , Haoyuan Shi , Zhenyu Yue

Cancer is a complex disease characterized by uncontrolled cell growth and proliferation. T cell receptors (TCRs) are essential proteins for the adaptive immune system, and their specific recognition of antigens plays a crucial role in the…

Machine Learning · Computer Science 2023-09-07 Zahra Tayebi , Sarwan Ali , Prakash Chourasia , Taslim Murad , Murray Patterson

Predicting clinical outcomes to anti-cancer drugs on a personalized basis is challenging in cancer treatment due to the heterogeneity of tumors. Traditional computational efforts have been made to model the effect of drug response on…

Machine Learning · Computer Science 2022-07-12 Jie Gao , Jing Hu , Wanqing Sun , Yili Shen , Xiaonan Zhang , Xiaomin Fang , Fan Wang , Guodong Zhao
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