circVDJ-seq for T cell clonotype detection in single-cell and spatial multi-omics
Plumbom, I.; Obermayer, B.; Raspe, R.; Pascual-Reguant, A.; Theurillat, I.; Pentimalli, T. M.; Hsieh, Y.-H.; Gil, M.; Dietrich, C.; Seeger-Zografakis, M.; Quedenau, C.; Wilde, J.; Braeuning, C.; Fischer, C.; Schuelke, M.; Ludwig, L. S.; Eggert, A.; Rajewsky, N.; Borodina, T.; Beule, D.; Altmueller, J.; Radbruch, H.; Hauser, A.; Conrad, T.
Show abstract
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.
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