ArticleScience advances2024
T cell receptor-centric perspective to multimodal single-cell data analysis.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Towards high-quality large-scale T cell receptor antigen specificity data: challenges and promises.Nature methods · 2026Article
- The Role of the T Cell Receptor Sequence in Shaping T Cell Functional Fate.Immunological reviews · 2026Review
- Machine Learning for TCR Repertoire Epitope Annotation and Pattern Discovery.Immunological reviews · 2026Review
- Insights, opportunities, and challenges provided by large cell atlases.Genome biology · 2025Review
- Sketching T cell atlases in the single-cell era: challenges and recommendations.Immunology and cell biology · 2025Review
- Heterogeneity of the liver cancer tumor microenvironment: mitochondrial metabolism and causal inference through Mendelian randomization.Discover oncology · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The T cell receptor (TCR), despite its importance, is underutilized in single-cell analysis, with gene expression features solely driving current strategies. Here, we argue for a TCR-first approach, more suited toward T cell repertoires. To this end, we curated a large T cell atlas from 12 prominent human studies, containing in total 500,000 T cells spanning multiple diseases, including melanoma, head and neck cancer, blood cancer, and lung transplantation. Here, we identified severe limitations in cell-type annotation using unsupervised approaches and propose a more robust standard using a semi-supervised method or the TCR arrangement. We showcase the utility of a TCR-first approach through application of the STEGO.R tool for the identification of treatment-related dynamics and previously unknown public T cell clusters with potential antigen-specific properties. Thus, the paradigm shift to a TCR-first can highlight overlooked key T cell features that have the potential for improvements in immunotherapy and diagnostics.
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Registered trials
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