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Single-cell immune repertoire analysis

Nature Methods (2024)Cite this article

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Abstract

Single-cell T cell and B cell antigen receptor-sequencing data analysis can potentially perform in-depth assessments of adaptive immune cells that inform on understanding immune cell development to tracking clonal expansion in disease and therapy. However, it has been extremely challenging to analyze and interpret T cells and B cells and their adaptive immune receptor repertoires at the single-cell level due to not only the complexity of the data but also the underlying biology. In this Review, we delve into the computational breakthroughs that have transformed the analysis of single-cell T cell and B cell antigen receptor-sequencing data.

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Fig. 1: Typical workflow of scTCR/BCR-seq.
Fig. 2: scTCR/BCR-seq data processing considerations.
Fig. 3: Multimodal integration of TCR with other single-cell data modes.
Fig. 4: scTCR/BCR-seq analysis in COVID-19, T cell development and tumor immunology.

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Acknowledgements

We thank G. Sturm for the useful discussions and D. Maresco-Pennisi and C. Lee for helping to proofread the document. We acknowledge Children’s Hospital Foundation’s philanthropic contributions awarded to the Ian Frazer Centre for Children’s Immunotherapy Research.

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Author notes

  1. These authors contributed equally: Sergio E. Irac, Megan Sioe Fei Soon.

Authors and Affiliations

  1. Cancer Immunoregulation and Immunotherapy, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

    Sergio E. Irac

  2. Ian Frazer Centre for Children’s Immunotherapy Research, Child Health Research Centre, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia

    Megan Sioe Fei Soon & Zewen Kelvin Tuong

  3. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA

    Nicholas Borcherding

  4. Omniscope, Palo Alto, CA, USA

    Nicholas Borcherding

  5. Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia

    Zewen Kelvin Tuong

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Contributions

S.E.I., N.B. and Z.K.T. wrote the original draft. S.E.I. and Z.K.T. synthesized the literature and designed the review structure. M.S.F.S., N.B. and Z.K.T. critically reviewed, revised and edited the manuscript. M.S.F.S. made and synthesized the figures and tables. Z.K.T. conceptualized the review, outlined the structure, provided overall direction and supervised the writing.

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Correspondence to Zewen Kelvin Tuong.

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Competing interests

N.B. is Head of Computational Biology at Omniscope and has consulted for Starling Biosciences and Santa Ana Bio. Z.K.T. has consulted for Synteny Biotechnology in the last 3 years. All other authors declare no competing interests.

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Nature Methods thanks Caleb Lareau, Guideng Li, and Tao Wang for their contribution to the peer review of this work. Primary Handling Editor: Madhura Mukhopadhyay, in collaboration with the Nature Methods team.

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Irac, S.E., Soon, M.S.F., Borcherding, N. et al. Single-cell immune repertoire analysis. Nat Methods (2024). https://doi.org/10.1038/s41592-024-02243-4

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