文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

Deep learning-based prediction of the T cell receptor-antigen binding specificity.

作者信息

Lu Tianshi, Zhang Ze, Zhu James, Wang Yunguan, Jiang Peixin, Xiao Xue, Bernatchez Chantale, Heymach John V, Gibbons Don L, Wang Jun, Xu Lin, Reuben Alexandre, Wang Tao

机构信息

Quantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA, 75390.

Department of Thoracic/Head & Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX USA, 77030.

出版信息

Nat Mach Intell. 2021 Oct;3(10):864-875. doi: 10.1038/s42256-021-00383-2. Epub 2021 Sep 23.


DOI:10.1038/s42256-021-00383-2
PMID:36003885
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9396750/
Abstract

Neoantigens play a key role in the recognition of tumor cells by T cells. However, only a small proportion of neoantigens truly elicit T cell responses, and fewer clues exist as to which neoantigens are recognized by which T cell receptors (TCRs). We built a transfer learning-based model, named pMHC-TCR binding prediction network (pMTnet), to predict TCR-binding specificities of neoantigens, and T cell antigens in general, presented by class I major histocompatibility complexes (pMHCs). pMTnet was comprehensively validated by a series of analyses, and showed advance over previous work by a large margin. By applying pMTnet in human tumor genomics data, we discovered that neoantigens were generally more immunogenic than self-antigens, but HERV-E, a special type of self-antigen that is re-activated in kidney cancer, is more immunogenic than neoantigens. We further discovered that patients with more clonally expanded T cells exhibiting better affinity against truncal, rather than subclonal, neoantigens, had more favorable prognosis and treatment response to immunotherapy, in melanoma and lung cancer but not in kidney cancer. Predicting TCR-neoantigen/antigen pairs is one of the most daunting challenges in modern immunology. However, we achieved an accurate prediction of the pairing only using the TCR sequence (CDR3β), antigen sequence, and class I MHC allele, and our work revealed unique insights into the interactions of TCRs and pMHCs in human tumors using pMTnet as a discovery tool.

摘要

相似文献

[1]
Deep learning-based prediction of the T cell receptor-antigen binding specificity.

Nat Mach Intell. 2021-10

[2]
pan-MHC and cross-Species Prediction of T Cell Receptor-Antigen Binding.

bioRxiv. 2023-12-12

[3]
The identification of effective tumor-suppressing neoantigens using a tumor-reactive TIL TCR-pMHC ternary complex.

Exp Mol Med. 2024-6

[4]
Immune-based mutation classification enables neoantigen prioritization and immune feature discovery in cancer immunotherapy.

Oncoimmunology. 2021-1-15

[5]
Utilizing immunogenomic approaches to prioritize targetable neoantigens for personalized cancer immunotherapy.

Front Immunol. 2023

[6]
Virus-like particle-mediated delivery of structure-selected neoantigens demonstrates immunogenicity and antitumoral activity in mice.

J Transl Med. 2024-1-3

[7]
A structural-based machine learning method to classify binding affinities between TCR and peptide-MHC complexes.

Mol Immunol. 2021-11

[8]
Immunological ignorance is an enabling feature of the oligo-clonal T cell response to melanoma neoantigens.

Proc Natl Acad Sci U S A. 2019-11-4

[9]
Functional analysis of peripheral and intratumoral neoantigen-specific TCRs identified in a patient with melanoma.

J Immunother Cancer. 2021-9

[10]
Structure-Based, Rational Design of T Cell Receptors.

Front Immunol. 2013-9-12

引用本文的文献

[1]
Constructing the cure: engineering the next wave of antibody and cellular immune therapies.

J Immunother Cancer. 2025-8-25

[2]
TCR-pMHC Binding Specificity Prediction From Structure Using Graph Neural Networks.

IEEE Trans Comput Biol Bioinform. 2025

[3]
Neoantigen-driven personalized tumor therapy: An update from discovery to clinical application.

Chin Med J (Engl). 2025-9-5

[4]
TCR-epiDiff: solving dual challenges of TCR generation and binding prediction.

Bioinformatics. 2025-7-1

[5]
G2VTCR: predicting antigen binding specificity by Weisfeiler-Lehman graph embedding of T cell receptor sequences.

bioRxiv. 2025-5-4

[6]
A roadmap for T cell receptor-peptide-bound major histocompatibility complex binding prediction by machine learning: glimpse and foresight.

Brief Bioinform. 2025-7-2

[7]
nuTCRacker: Predicting the Recognition of HLA-I-Peptide Complexes by αβTCRs for Unseen Peptides.

Eur J Immunol. 2025-7

[8]
Computation strategies and clinical applications in neoantigen discovery towards precision cancer immunotherapy.

Biomark Res. 2025-7-9

[9]
Benchmarking of T cell receptor-epitope predictors with ePytope-TCR.

Cell Genom. 2025-6-27

[10]
Computational methods and data resources for predicting tumor neoantigens.

Brief Bioinform. 2025-7-2

本文引用的文献

[1]
Mapping the functional landscape of T cell receptor repertoires by single-T cell transcriptomics.

Nat Methods. 2021-1

[2]
Deep Learning in Protein Structural Modeling and Design.

Patterns (N Y). 2020-11-12

[3]
Tumor neoantigenicity assessment with CSiN score incorporates clonality and immunogenicity to predict immunotherapy outcomes.

Sci Immunol. 2020-2-21

[4]
Detection of Enriched T Cell Epitope Specificity in Full T Cell Receptor Sequence Repertoires.

Front Immunol. 2019-11-29

[5]
Integrative molecular and clinical modeling of clinical outcomes to PD1 blockade in patients with metastatic melanoma.

Nat Med. 2019-12-2

[6]
Attention mechanism enhanced LSTM with residual architecture and its application for protein-protein interaction residue pairs prediction.

BMC Bioinformatics. 2019-11-27

[7]
T cell receptor next-generation sequencing reveals cancer-associated repertoire metrics and reconstitution after chemotherapy in patients with hematological and solid tumors.

Oncoimmunology. 2019-7-25

[8]
VDJdb in 2019: database extension, new analysis infrastructure and a T-cell receptor motif compendium.

Nucleic Acids Res. 2020-1-8

[9]
T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes.

Cell. 2019-8-8

[10]
PIRD: Pan Immune Repertoire Database.

Bioinformatics. 2020-2-1

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索