Identifying T-cell clubs by embracing the local harmony between TCR and gene expressions
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 sequencin...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2024-11-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s44320-024-00070-5 |
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| Summary: | 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. |
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| ISSN: | 1744-4292 |