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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

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

Most statistical classifiers are designed to find patterns in data where numbers fit into rows and columns, like in a spreadsheet, but many kinds of data do not conform to this structure. To uncover patterns in non-conforming data, we…

Quantitative Methods · Quantitative Biology 2021-03-22 Jared Ostmeyer , Scott Christley , Lindsay Cowell

Hypervariable T-cell receptors (TCR) play a key role in adaptive immunity, recognising a vast diversity of pathogen-derived antigens. High throughput sequencing of TCR repertoires (RepSeq) produces huge datasets of T-cell receptor sequences…

Early detection of cancers has been much explored due to its paramount importance in biomedical fields. Among different types of data used to answer this biological question, studies based on T cell receptors (TCRs) are under recent…

Machine Learning · Statistics 2022-08-10 Younghoon Kim , Tao Wang , Danyi Xiong , Xinlei Wang , Seongoh Park

The binding affinity between the T-cell receptors (TCRs) and antigenic peptides mainly determines immunological recognition. It is not a trivial task that T cells identify the digital sequences of peptide amino acids by simply relying on…

Cell Behavior · Quantitative Biology 2024-02-14 Jin Xu , Junghyo Jo

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

T lymphocytes (T cells) orchestrate adaptive immune responses upon activation. T cell activation requires sufficiently strong binding of T cell receptors (TCRs) on their surface to short peptides (p) derived from foreign proteins, which are…

Biological Physics · Physics 2016-06-22 Andrej Kosmrlj , Arup K. Chakraborty , Mehran Kardar , Eugene I. Shakhnovich

We are frequently faced with a large collection of antibodies, and want to select those with highest affinity for their cognate antigen. When developing a first-line therapeutic for a novel pathogen, for instance, we might look for such…

Populations and Evolution · Quantitative Biology 2021-01-27 Duncan K. Ralph , Frederick A. Matsen

Studies of T cells and their clonally unique receptors have shown promise in elucidating the association between immune response and human disease. Methods to identify T-cell receptor clones which expand or contract in response to certain…

Methodology · Statistics 2025-02-10 David Swanson , Alexander Sherry , Chad Tang

In protein biophysics, the separation between the functionally important residues (forming the active site or binding surface) and those that create the overall structure (the fold) is a well-established and fundamental concept. Identifying…

Biomolecules · Quantitative Biology 2023-10-17 Tianxiao Li , Hongyu Guo , Filippo Grazioli , Mark Gerstein , Martin Renqiang Min

Identifying T-cell receptors (TCRs) that interact with antigenic peptides provides the technical basis for developing vaccines and immunotherapies. The emergent deep learning methods excel at learning antigen binding patterns from known…

Quantitative Methods · Quantitative Biology 2024-11-28 Jiangbin Zheng , Qianhui Xu , Ruichen Xia , Stan Z. Li

The set of T cells that express the same T cell receptor (TCR) sequence represents a T cell clone. The number of different naive T cell clones in an organism reflects the number of different T cell receptors (TCRs) arising from…

Populations and Evolution · Quantitative Biology 2020-03-06 Renaud Dessalles , Yunbei Pan , Mingtao Xia , Davide Maestrini , Maria R. D'Orsogna , Tom Chou

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

T-cell receptor (TCR) repertoire data contain information about infections that could be used in disease diagnostics and vaccine development, but extracting that information remains a major challenge. Here we developed a statistical…

The molecular recognition of T-cell receptors is the hallmark of the adaptive immunity. Given the finiteness of the T-cell repertoire, individual T-cell receptors are necessary to be cross-reactive to multiple antigenic peptides. In this…

Cell Behavior · Quantitative Biology 2024-02-15 Jin Xu , Junghyo Jo

Understanding the structure of the human T-cell receptor repertoire is a crucial precondition to understand the ability of the immune system to recognize and respond to antigens. T-cells are often compared via the complementarity…

Molecular Networks · Quantitative Biology 2021-12-14 Paul Richter

Examination of T-cell receptor (TCR) clonality has become a way of understanding immunologic response to cancer and its interventions in recent years. An aspect of these analyses is determining which receptors expand or contract…

Quantitative Methods · Quantitative Biology 2026-01-09 David Swanson , Alexander Sherry , Cara Haymaker , Alexandre Reuben , Chad Tang

B cell receptors (BCRs) play a crucial role in recognizing and fighting foreign antigens. High-throughput sequencing enables in-depth sampling of the BCRs repertoire after immunization. However, only a minor fraction of BCRs actively…

Populations and Evolution · Quantitative Biology 2023-12-22 Maria Francesca Abbate , Thomas Dupic , Emmanuelle Vigne , Melody A. Shahsavarian , Aleksandra M. Walczak , Thierry Mora

Motivation: The activity of the adaptive immune system is governed by T-cells and their specific T-cell receptors (TCR), which selectively recognize foreign antigens. Recent advances in experimental techniques have enabled sequencing of…

Biomolecules · Quantitative Biology 2023-08-28 Anna Weber , Jannis Born , María Rodríguez Martínez