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T cell receptor (TCR) repertoires encode critical immunological signatures for autoimmune diseases, yet their clinical application remains limited by sequence sparsity and low witness rates. We developed EAMil, a multi-instance deep…

Machine Learning · Computer Science 2025-11-25 Ruihao Zhang , Mao chen , Fei Ye , Dandan Meng , Yixuan Huang , Xiao Liu

Antigen-specific T cells play an essential role in immunoregulation and diseases such as cancer. Characterizing the T cell receptor (TCR) sequences that encode T cell specificity is critical for elucidating the antigenic determinants of…

Designing full-length, epitope-specific TCR {\alpha}\b{eta} remains challenging due to vast sequence space, data biases and incomplete modeling of immunogenetic constraints. We present LSMTCR, a scalable multi-architecture framework that…

Computational Engineering, Finance, and Science · Computer Science 2025-10-09 Ruihao Zhang , Xiao Liu

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…

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

The vertebrate immune system is a wonder of modern evolution. Occasionally, however, correlations within the immune system lead to inappropriate recruitment of preexisting T cells against novel viral diseases. We present a random energy…

Biomolecules · Quantitative Biology 2009-11-10 Jeong-Man Park , Michael W. Deem

To ensure faithful information transmission, cells utilize nonequilibrium drives to reduce errors. Kinetic proofreading is a classic mechanism known to sharpen ligand discrimination by T lymphocytes. It remains an open question whether the…

Biological Physics · Physics 2025-09-23 Qing Xu , Shenshen Wang

Physicochemically informed biological sequence generation has the potential to accelerate computer-aided cellular therapy, yet current models fail to \emph{jointly} ensure novelty, diversity, and biophysical plausibility when designing…

Computational Engineering, Finance, and Science · Computer Science 2025-10-08 Jiahao Ma , Hongzong Li , Ye-Fan Hu , Jian-Dong Huang

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

Traditional vaccines against viruses are designed to target their surface proteins, i.e., antigens, which can trigger the immune system to produce specific antibodies to capture and neutralize the viruses. However, viruses often evolve…

Populations and Evolution · Quantitative Biology 2020-03-25 Rui Qiao , Ngoc Hieu Tran , Baozhen Shan , Ali Ghodsi , Ming Li

T cells form intriguing patterns during adhesion to antigen-presenting cells. The patterns at the cell-cell contact zone are composed of two types of domains, which either contain short TCR/MHCp receptor-ligand complexes or the longer…

Subcellular Processes · Quantitative Biology 2009-11-10 Thomas R. Weikl , Reinhard Lipowsky

The adaptive immune system constantly remodels its lymphocyte repertoire for better protection against future pathogens. Its ability to improve antigen recognition on the fly relies on somatic mutation and selective expansion of B…

Biological Physics · Physics 2022-09-29 Hongda Jiang , Shenshen Wang

The efficient recognition of pathogens by the adaptive immune system relies on the diversity of receptors displayed at the surface of immune cells. T-cell receptor diversity results from an initial random DNA editing process, called VDJ…

Populations and Evolution · Quantitative Biology 2015-04-28 Yuval Elhanati , Anand Murugan , Curtis G. Callan , Thierry Mora , Aleksandra M. Walczak

Artificial intelligence (AI) is accelerating progress in modeling T and B cell receptors by enabling predictive and generative frameworks grounded in sequence data and immune context. This chapter surveys recent advances in the use of…

Biomolecules · Quantitative Biology 2026-01-30 Linhui Xie , Aurelien Pelissier , Yanjun Shao , Maria Rodriguez Martinez

One primary goal of precision medicine is to estimate the individualized treatment rules (ITRs) that optimize patients' health outcomes based on individual characteristics. Health studies with multiple treatments are commonly seen in…

Methodology · Statistics 2025-05-07 Xuqiao Li , Qiuyan Zhou , Ying Wu , Ying Yan

Following antigen stimulation, the net outcomes of a T cell response are shaped by integrated signals from both positive co-stimulatory and negative regulatory molecules. Recently, the blockade of negative regulatory molecules (i.e. immune…

Cell Behavior · Quantitative Biology 2017-09-19 Haidong Dong , Yiyi Yan , Roxana S. Dronca , Svetomir N. Markovic

The study of cells and their responses to genetic or chemical perturbations promises to accelerate the discovery of therapeutic targets. However, designing adequate and insightful models for such data is difficult because the response of a…

Machine Learning · Computer Science 2024-12-04 Haiyi Mao , Romain Lopez , Kai Liu , Jan-Christian Hütter , David Richmond , Panayiotis V. Benos , Lin Qiu

Diverse repertoires of hypervariable immunoglobulin receptors (TCR and BCR) recognize antigens in the adaptive immune system. The development of immunoglobulin receptor repertoire sequencing methods makes it possible to perform…

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

Purpose: MRI cell tracking can be used to monitor immune cells involved in the immunotherapy response, providing insight into the mechanism of action, temporal progression of tumour growth and individual potency of therapies. To evaluate…