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Comprehensive mapping of tissue cell architecture via integrated single cell and spatial transcriptomics

By Vitalii Kleshchevnikov, Artem Shmatko, Emma Dann, Alexander Aivazidis, Hamish W King, Tong Li, Artem Lomakin, Veronika Kedlian, Mika Sarkin Jain, Jun Sung Park, Lauma Ramona, Elizabeth Tuck, Anna Arutyunyan, Roser Vento-Tormo, Moritz Gerstung, Louisa James, Oliver Stegle, Omer Ali Bayraktar

Posted 17 Nov 2020
bioRxiv DOI: 10.1101/2020.11.15.378125

The spatial organization of cell types in tissues fundamentally shapes cellular interactions and function, but the high-throughput spatial mapping of complex tissues remains a challenge. We present cell2location, a principled and versatile Bayesian model that integrates single-cell and spatial transcriptomics to map cell types in situ in a comprehensive manner. We show that cell2location outperforms existing tools in accuracy and comprehensiveness and we demonstrate its utility by mapping two complex tissues. In the mouse brain, we use a new paired single nucleus and spatial RNA-sequencing dataset to map dozens of cell types and identify tissue regions in an automated manner. We discover novel regional astrocyte subtypes including fine subpopulations in the thalamus and hypothalamus. In the human lymph node, we resolve spatially interlaced immune cell states and identify co-located groups of cells underlying tissue organisation. We spatially map a rare pre-germinal centre B-cell population and predict putative cellular interactions relevant to the interferon response. Collectively our results demonstrate how cell2location can serve as a versatile first-line analysis tool to map tissue architectures in a high-throughput manner. ### Competing Interest Statement The authors have declared no competing interest.

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