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Abstract
Spatial transcriptomic technologies promise to resolve cellular wiring diagrams of tissues in health and disease, but comprehensive mapping of cell types in situ remains a challenge. Here we present сell2location, a Bayesian model that can resolve fine-grained cell types in spatial transcriptomic data and create comprehensive cellular maps of diverse tissues. Cell2location accounts for technical sources of variation and borrows statistical strength across locations, thereby enabling the integration of single-cell and spatial transcriptomics with higher sensitivity and resolution than existing tools. We assessed cell2location in three different tissues and show improved mapping of fine-grained cell types. In the mouse brain, we discovered fine regional astrocyte subtypes across the thalamus and hypothalamus. In the human lymph node, we spatially mapped a rare pre-germinal center B cell population. In the human gut, we resolved fine immune cell populations in lymphoid follicles. Collectively, our results present сell2location as a versatile analysis tool for mapping tissue architectures in a comprehensive manner.
A Bayesian model maps the location of cell types in tissues with higher sensitivity.
Details
; Shmatko Artem 2
; Dann, Emma 1
; Aivazidis Alexander 1 ; King, Hamish W 3
; Li, Tong 1
; Elmentaite Rasa 1
; Lomakin Artem 4
; Kedlian Veronika 1 ; Gayoso Adam 5
; Jain, Mika Sarkin 6 ; Park, Jun Sung 7
; Lauma, Ramona 1 ; Tuck, Elizabeth 1 ; Arutyunyan Anna 1
; Vento-Tormo Roser 1
; Gerstung Moritz 4
; James, Louisa 8
; Stegle Oliver 9
; Bayraktar, Omer Ali 1
1 Wellcome Sanger Institute, Hinxton, Cambridge, UK (GRID:grid.10306.34) (ISNI:0000 0004 0606 5382)
2 Wellcome Sanger Institute, Hinxton, Cambridge, UK (GRID:grid.10306.34) (ISNI:0000 0004 0606 5382); Moscow State University, Leninskie Gory, Moscow, Russia (GRID:grid.14476.30) (ISNI:0000 0001 2342 9668)
3 Wellcome Sanger Institute, Hinxton, Cambridge, UK (GRID:grid.10306.34) (ISNI:0000 0004 0606 5382); Blizard Institute, Queen Mary University of London, Centre for Immunobiology, London, UK (GRID:grid.4868.2) (ISNI:0000 0001 2171 1133)
4 European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Hinxton, UK (GRID:grid.225360.0) (ISNI:0000 0000 9709 7726); Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany (GRID:grid.4709.a) (ISNI:0000 0004 0495 846X)
5 University of California, Berkeley, Center for Computational Biology, Berkeley CA, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878)
6 Wellcome Sanger Institute, Hinxton, Cambridge, UK (GRID:grid.10306.34) (ISNI:0000 0004 0606 5382); University of Cambridge, Theory of Condensed Matter, Department of Physics, Cavendish Laboratory, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934)
7 Wellcome Sanger Institute, Hinxton, Cambridge, UK (GRID:grid.10306.34) (ISNI:0000 0004 0606 5382); European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Hinxton, UK (GRID:grid.225360.0) (ISNI:0000 0000 9709 7726)
8 Blizard Institute, Queen Mary University of London, Centre for Immunobiology, London, UK (GRID:grid.4868.2) (ISNI:0000 0001 2171 1133)
9 Wellcome Sanger Institute, Hinxton, Cambridge, UK (GRID:grid.10306.34) (ISNI:0000 0004 0606 5382); Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany (GRID:grid.4709.a) (ISNI:0000 0004 0495 846X); German Cancer Research Center (DKFZ), Division of Computational Genomics and Systems Genetics, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584)