基于大模型的MHC Ⅱ抗原肽-T细胞受体结合预测  

Prediction of MHC Ⅱ antigen peptide-T cell receptors binding based on foundation model

作　　者：许珉瑞 张斯文 鲁曼曼 高媛 张梦欢 林勇[1] 谢鹭 XU Minrui;ZHANG Siwen;LU Manman;GAO Yuan;ZHANG Menghuan;LIN Yong;XIE Lu(School of Health Science and Engineering,University of Shanghai for Science and Technology,Shanghai 200093,P.R.China;Shanghai-MOST Key Laboratory of Health and Disease Genomics,Shanghai Institute for Biomedical and Pharmaceutical Technologies,Shanghai 200237,P.R.China;Shanghai Institute for Biomedical and Pharmaceutical Technologies,Fudan University,Shanghai 200237,P.R.China;School of Life Science and Technology,Tongji University,Shanghai 200092,P.R.China)

机构地区：[1]上海理工大学健康科学与工程学院,上海200093 [2]上海市生物医药技术研究院上海市疾病与健康基因组学重点实验室,上海200237 [3]复旦大学上海市生物医药技术研究院,上海200237 [4]同济大学生命科学与技术学院,上海200092

出　　处：《生物医学工程学杂志》2024年第6期1243-1249,共7页Journal of Biomedical Engineering

基　　金：国家自然科学基金(31870829);上海市卫健委协同创新集群项目(2019CXJQ02)。

摘　　要：T细胞受体(TCR)与抗原肽的特异性结合在调节和介导免疫的过程中发挥着关键作用,为肿瘤疫苗设计提供了必要的基础。近年来的研究主要集中在主要组织相容性复合体(MHC)Ⅰ类抗原的TCR预测,针对MHCⅡ类抗原的TCR预测研究尚不充分,仍存在较大的提升空间。本研究利用ProtT5大模型进行MHCⅡ类抗原肽和TCR结合预测研究,探究其特征提取能力。此外,对模型进行微调,并构建前馈神经网络结构进行融合从而实现预测模型。实验结果显示,本研究提出的方法较传统方法表现更佳,预测准确度达到0.96,AUC达到0.93,验证了本文提出模型的有效性。The specific binding of T cell receptors(TCRs)to antigenic peptides plays a key role in the regulation and mediation of the immune process and provides an essential basis for the development of tumour vaccines.In recent years,studies have mainly focused on TCR prediction of major histocompatibility complex(MHC)class Ⅰ antigens,but TCR prediction of MHC class Ⅱ antigens has not been sufficiently investigated and there is still much room for improvement.In this study,the combination of MHC class Ⅱ antigen peptide and TCR prediction was investigated using the ProtT5 grand model to explore its feature extraction capability.In addition,the model was fine-tuned to retain the underlying features of the model,and a feed-forward neural network structure was constructed for fusion to achieve the prediction model.The experimental results showed that the method proposed in this study performed better than the traditional methods,with a prediction accuracy of 0.96 and an AUC of 0.93,which verifies the effectiveness of the model proposed in this paper.

关 键 词：MHCⅡ抗原肽-T细胞受体结合预测 大模型 ProtT5模型 免疫治疗 

分 类 号：R730.51[医药卫生—肿瘤]