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

Monitoring T cell clonality in human tissues provides important insights into adaptive immune response mechanisms in cancer, infectious diseases, and autoimmunity. However, retrieving VDJ sequence information from single-cell and spatial transcriptomics workflows with 3’-barcoding of cDNA remains resource-intensive or requires specialized sequencing equipment. Here, we introduce circVDJ-seq for simplified and cost-efficient TCR profiling from 3’-directed workflows such as single-nucleus RNA sequencing, RNA+ATAC multi-omics, and spatial transcriptomics. Application of circVDJ-seq to freshly resected neuroblastomas, and post-mortem lymph nodes affected by pneumonia or COVID-19 reveals distinct immune microenvironments and T cell clonality patterns, highlighting broad utility across diverse clinical contexts.