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Single cell antigen receptor analysis reveals lymphocyte developmental origins

Suo, C.; Polanski, K.; Dann, E.; Lindeboom, R. G. H.; Vilarrasa Blasi, R.; Vento-Tormo, R.; Haniffa, M.; Meyer, K. B.; Tuong, Z. K.; Clatworthy, M. R.; Teichmann, S.

2022-11-19 immunology
10.1101/2022.11.18.517068 bioRxiv
Show abstract

Assessment of single-cell gene expression (scRNA-seq) and adaptive immune receptor sequencing (scVDJ-seq) has been invaluable in studying lymphocyte biology. Here, we introduce Dandelion, a computational pipeline for scVDJ-seq analysis. It enables the application of standard V(D)J analysis workflows to single-cell datasets, delivering improved V(D)J contig annotation and the identification of non-productive and partially spliced contigs. We devised a novel strategy to create an adaptive immune receptor feature space that can be used for both differential V(D)J usage analysis and pseudotime trajectory inference. The application of Dandelion improved the alignment of human thymic development trajectories of double positive T cells to mature single-positive CD4/CD8 T cells, with important new predictions of factors regulating lineage commitment. Dandelion analysis of other cell compartments provided novel insights into the origins of human B1 cells and ILC/NK cell development, illustrating the power of our approach. Dandelion is an open access resource (https://www.github.com/zktuong/dandelion) that will enable future discoveries.

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