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Links between T cell clonotypes, as defined by T cell receptor (TCR) sequences, and phenotype, as reflected in gene expression (GEX) profiles, surface protein expression and peptide:major histocompatibility complex binding, can reveal functional relationships beyond the features shared by clonally related cells. Here we present clonotype neighbor graph analysis (CoNGA), a graph theoretic approach that identifies correlations between GEX profile and TCR sequence through statistical analysis of GEX and TCR similarity graphs. Using CoNGA, we uncovered associations between TCR sequence and GEX profiles that include a previously undescribed 'natural lymphocyte' population of human circulating CD8 T cells and a set of TCR sequence determinants of differentiation in thymocytes. These examples show that CoNGA might help elucidate complex relationships between TCR sequence and T cell phenotype in large, heterogeneous, single-cell datasets.
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http://dx.doi.org/10.1038/s41587-021-00989-2 | DOI Listing |
Nucleic Acids Res
September 2025
Department of Thoracic Surgery, West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu 610041, China.
T-cell receptor (TCR) repertoire sequencing allows researchers to analyze millions of TCRs, providing unparalleled precision in understanding immune responses and enabling broad applications. However, existing TCR-related databases are based on a limited number of samples. Here, we present TCRdb2.
View Article and Find Full Text PDFZhonghua Bing Li Xue Za Zhi
September 2025
Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
To investigate the clinicopathological and genetic characteristics of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). The forty-two MEITL cases diagnosed in the Department of Pathology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China from 2016 to 2022 was retrospectively analyzed. Clinical data were collected, and follow-up was performed.
View Article and Find Full Text PDFPLoS One
September 2025
Dongguan TCM Hospital of Guangzhou University of Chinese Medicine, Dongguan, China.
Background: Although previous studies suggested associations between psoriasis and atopic dermatitis (AD), the directionality and causality of these relationships remain controversial. This study employed bidirectional Mendelian randomization to investigate the potential causal relationships between these two inflammatory skin conditions.
Methods: Genome-wide association statistics were obtained for psoriasis and AD from large-scale consortia and meta-analyses of genome-wide association studies.
Sci Immunol
September 2025
Laboratory of Epigenetics and Immunology, West China Institute of Women and Children's Health, NHC Key Laboratory of Chronobiology, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.
Naïve T cells are maintained in a homeostatic state to preserve a stable T cell pool with diverse T cell receptor (TCR) repertoires, ensuring preparedness for priming. However, the underlying mechanisms controlling naïve T cell homeostasis and priming remain unclear. Leveraging a machine learning-based functional genetic screen, we identified () as the top factor responsible for naïve T cell homeostasis.
View Article and Find Full Text PDFThe addition of aPD1 to 5-FU/platinum in advanced gastric cancer (GC) yields variable responses. To understand cooperativity between chemotherapy and immunotherapy, we previously reported a phase II trial sequentially adding pembrolizumab to 5-FU/platinum. In this study, we use single-cell RNA- and TCR-sequencing to analyze 66,813 T cells from primary tumor biopsies pre-treatment, post-chemotherapy, and post-immunotherapy in 33 patients.
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