T cell receptor–centric perspective to multimodal single-cell data analysis

2024/11/29 by Kerry A. Mullan, My Kieu Ha, Sebastiaan Valkiers +4 · 2 voices · 5 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Bioinformatics #Biology #Cancer #Cancer immunotherapy #Cell #Computational biology #Computer science #Genetics #Immune Cell Function and Interaction #Immune system #Immunology #Immunotherapy #Single-cell and spatial transcriptomics #T cell #T-cell and B-cell Immunology #T-cell receptor

paper · pdf · doi:10.1126/sciadv.adr3196

openalex publication_date 2024/11/29 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22

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.

Cited by

• AIRRWAS integrates TCR-microbiome data to reveal how the gut microbiome shapes the circulating and mucosal T cell repertoire
• Sketching T cell atlases in the single-cell era: challenges and recommendations. [europepmc]
• Heterogeneity of the liver cancer tumor microenvironment: mitochondrial metabolism and causal inference through Mendelian randomization. [europepmc]
• Insights, opportunities, and challenges provided by large cell atlases. [europepmc]
• T cell-microbiome associations captured through T cell receptor convergence analysis [europepmc]

Discussions

• Our massive effort to recontextualize #single #T-cell data is now out in Science Advances! We developed a new system, STEGO, to do a TCR-first analysis, and reanalyzed 12 studies and more than 500 000 [bsky, 49 points, 5 comments]
• A new paper, led by Kerry Mullan from Pieter Meysman’s (@pmeysman.bsky.social) group, advocates for a TCR-centric approach to analyzing scRNA data from T cells. One highlight is the identification of [bsky, 4 points, 0 comments]

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