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.