Identifying T cell antigen at the atomic level with graph convolutional network

Abstract Precise identification of T cell antigens in silico is crucial for the development of cancer mRNA vaccines. However, current computational methods only utilize sequence-level rather than atomic level features to identify T cell antigens, which results in poor representation of those that ac...

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Main Authors: Jinhao Que, Guangfu Xue, Tao Wang, Xiyun Jin, Zuxiang Wang, Yideng Cai, Wenyi Yang, Meng Luo, Qian Ding, Jinwei Zhang, Yilin Wang, Yuexin Yang, Fenglan Pang, Yi Hui, Zheng Wei, Jun Xiong, Shouping Xu, Yi Lin, Haoxiu Sun, Pingping Wang, Zhaochun Xu, Qinghua Jiang
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60461-6
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Summary:Abstract Precise identification of T cell antigens in silico is crucial for the development of cancer mRNA vaccines. However, current computational methods only utilize sequence-level rather than atomic level features to identify T cell antigens, which results in poor representation of those that activate immune responses. Here we propose deepAntigen, a graph convolutional network-based framework, to identify T cell antigens at the atomic level. deepAntigen achieves excellent performance both in the prediction of antigen-human leukocyte antigen (HLA) binding and antigen-T cell receptor (TCR) interactions, which can provide comprehensive guidance for identification of T cell antigens. The tumor neoantigens predicted by deepAntigen in lung, breast and pancreatic cancer patients are experimentally validated through ELISPOT assays, which detect successful activation of CD8+ T cells to release IFN-γ. Overall, deepAntigen can accurately identify T cell antigens at the atomic level, which could accelerate the development of personalized neoantigen targeted immunotherapies for cancer patients.
ISSN:2041-1723