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circVDJ-seq for T cell clonotype detection in single-cell and spatial multi-omics.

Izabela Plumbom1,2, Benedikt Obermayer2, Raphael Raspe3

  • 1Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.

Genome Medicine
|June 11, 2026
PubMed
Summary

This study introduces circVDJ-seq, a cost-efficient method for T cell receptor (TCR) profiling from standard sequencing workflows. This technique simplifies the analysis of immune responses in various diseases, including cancer and infections.

Keywords:
Adaptive immunitySingle-cell immune profilingSpatial transcriptomicsTCR sequencingTumor microenvironment

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Area of Science:

  • Immunology
  • Genomics
  • Bioinformatics

Background:

  • Monitoring T cell repertoires is crucial for understanding immune responses in cancer, infectious diseases, and autoimmunity.
  • Current methods for T cell receptor (TCR) VDJ profiling from 3'-barcoded transcriptomics are resource-intensive and require specialized equipment.

Purpose of the Study:

  • To introduce circVDJ-seq, a simplified and cost-efficient method for TCR profiling.
  • To enable TCR profiling from diverse 3'-directed workflows, including single-cell RNA sequencing, multi-omics, and spatial transcriptomics.

Main Methods:

  • Developed circVDJ-seq, a novel approach for TCR profiling.
  • Applied circVDJ-seq to analyze T cell repertoires in neuroblastomas and postmortem lymph nodes from pneumonia and COVID-19 cases.

Main Results:

  • circVDJ-seq offers a simplified and cost-efficient alternative for TCR profiling.
  • The method successfully revealed distinct immune microenvironments and T cell clonality patterns in various clinical contexts.
  • Demonstrated broad utility across diverse applications, including cancer and infectious diseases.

Conclusions:

  • circVDJ-seq facilitates efficient and accessible T cell repertoire analysis.
  • The method enhances the study of immune responses in complex diseases.
  • Highlights the potential of circVDJ-seq for broad clinical and research applications.