Yiping Zou, Jiaqi Luo, Lingxi Chen, Xueying Wang, Wei Liu, Ruo Han Wang, Shuai Cheng Li
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引用次数: 0
摘要
T细胞受体(TCR)和基因表达是了解T细胞的两个互补的重要方面,但它们的多样性给综合分析带来了挑战。我们介绍了 TCRclub,这是一种整合单细胞 RNA 测序数据和单细胞 TCR 测序数据的新方法,利用局部和谐来识别功能上相似的 T 细胞群,称为 "俱乐部"。我们将 TCRclub 应用于涵盖各种疾病的七个数据集的 298,106 个 T 细胞。首先,TCRclub 在对包含 400 多种经过验证的肽-主要组织相容性复合体类别的数据集上的 T 细胞进行聚类方面优于最先进的方法。第二,TCRclub揭示了胆管癌患者T细胞从活化到衰竭的转变过程。第三,TCRclub通过分析基底细胞癌患者治疗前和治疗后的样本,发现了可干预抗PD-1疗法反应的途径。此外,TCRclub 还揭示了 COVID-19 患者在不同严重程度下的不同 T 细胞反应和基因模式。因此,TCRclub 有助于开发更有效的癌症和传染病免疫治疗策略。
Identifying T-cell clubs by embracing the local harmony between TCR and gene expressions.
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.
期刊介绍:
Systems biology is a field that aims to understand complex biological systems by studying their components and how they interact. It is an integrative discipline that seeks to explain the properties and behavior of these systems.
Molecular Systems Biology is a scholarly journal that publishes top-notch research in the areas of systems biology, synthetic biology, and systems medicine. It is an open access journal, meaning that its content is freely available to readers, and it is peer-reviewed to ensure the quality of the published work.