通过把握T细胞受体(TCR)与基因表达之间的局部协调性来识别T细胞簇。

Identifying T-cell clubs by embracing the local harmony between TCR and gene expressions.

作者信息

Zou Yiping, Luo Jiaqi, Chen Lingxi, Wang Xueying, Liu Wei, Wang Ruo Han, Li Shuai Cheng

机构信息

Department of Computer Science, City University of Hong Kong, Hong Kong, China.

Department of Computer Science, City University of Hong Kong Shenzhen Research Institute, Shenzhen, China.

出版信息

Mol Syst Biol. 2024 Dec;20(12):1329-1345. doi: 10.1038/s44320-024-00070-5. Epub 2024 Nov 4.

Abstract

T cell receptors (TCR) and gene expression provide two complementary and essential aspects in T cell understanding, yet their diversity presents challenges in integrative analysis. We introduce TCRclub, a novel method integrating single-cell RNA sequencing data and single-cell TCR sequencing data using local harmony to identify functionally similar T cell groups, termed 'clubs'. We applied TCRclub to 298,106 T cells across seven datasets encompassing various diseases. First, TCRclub outperforms the state-of-the-art methods in clustering T cells on a dataset with over 400 verified peptide-major histocompatibility complex categories. Second, TCRclub reveals a transition from activated to exhausted T cells in cholangiocarcinoma patients. Third, TCRclub discovered the pathways that could intervene in response to anti-PD-1 therapy for patients with basal cell carcinoma by analyzing the pre-treatment and post-treatment samples. Furthermore, TCRclub unveiled different T-cell responses and gene patterns at different severity levels in patients with COVID-19. Hence, TCRclub aids in developing more effective immunotherapeutic strategies for cancer and infectious diseases.

摘要

T细胞受体(TCR)和基因表达为理解T细胞提供了两个互补且至关重要的方面,然而它们的多样性给综合分析带来了挑战。我们引入了TCRclub,这是一种利用局部和谐算法整合单细胞RNA测序数据和单细胞TCR测序数据的新方法,用于识别功能相似的T细胞群体,即“俱乐部”。我们将TCRclub应用于涵盖各种疾病的七个数据集中的298,106个T细胞。首先,在一个包含400多个经过验证的肽-主要组织相容性复合体类别的数据集上,TCRclub在T细胞聚类方面优于现有最先进的方法。其次,TCRclub揭示了胆管癌患者中从活化T细胞到耗竭T细胞的转变。第三,通过分析基底细胞癌患者治疗前和治疗后的样本,TCRclub发现了可能干预抗PD-1治疗反应的途径。此外,TCRclub揭示了COVID-19患者在不同严重程度水平下不同的T细胞反应和基因模式。因此,TCRclub有助于为癌症和传染病开发更有效的免疫治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1937/11612385/7af52214816b/44320_2024_70_Fig1_HTML.jpg

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