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

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Item Type:Preprint
Title:circVDJ-seq for T cell clonotype detection in single-cell and spatial multi-omics
Creators Name:Plumbom, Izabela, Obermayer, Benedikt, Raspe, Raphael, Pascual-Reguant, Anna, Theurillat, Ilan, Pentimalli, Tancredi M., Hsieh, Yu-Hsin, Gil, Marine, Dietrich, Carola, Seeger-Zografakis, Michaela, Quedenau, Claudia, Wilde, Jeannine, Braeuning, Caroline, Fischer, Cornelius, Schuelke, Markus, Ludwig, Leif S., Eggert, Angelika, Rajewsky, Nikolaus, Borodina, Tatiana, Beule, Dieter, Altmueller, Janine, Radbruch, Helena, Hauser, Anja and Conrad, Thomas
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.
Keywords:TCR Sequencing, Single-Cell Immune Profiling, Adaptive Immunity, Spatial Transcriptomics, Tumor Microenvironment
Source:bioRxiv
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2025.09.16.675546
Date:18 September 2025
Official Publication:https://doi.org/10.1101/2025.09.16.675546

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