RT Journal Article
SR Electronic
T1 Single cell antigen receptor analysis reveals lymphocyte developmental origins
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.18.517068
DO 10.1101/2022.11.18.517068
A1 Chenqu Suo
A1 Krzysztof Polanski
A1 Emma Dann
A1 Rik G.H. Lindeboom
A1 Roser Vilarrasa Blasi
A1 Roser Vento-Tormo
A1 Muzlifah Haniffa
A1 Kerstin B. Meyer
A1 Zewen Kelvin Tuong
A1 Menna R. Clatworthy
A1 Sarah A. Teichmann
YR 2022
UL http://biorxiv.org/content/early/2022/11/19/2022.11.18.517068.abstract
AB Assessment of single-cell gene expression (scRNA-seq) and antigen receptor sequencing (scVDJ-seq) has been invaluable in studying lymphocyte biology, but current tools are limited. 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 antigen 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.Competing Interest StatementIn the past three years, S.A.T. has received remuneration for Scientific Advisory Board Membership from Sanofi, GlaxoSmithKline, Foresite Labs and Qiagen. S.A.T. is a co-founder and holds equity in Transition Bio. Z.K.T. has received consulting fees from Synteny Biotechnologies Ltd on activities unrelated to this manuscript.