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

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, View ORCID ProfileOmer Ali Bayraktar
doi: https://doi.org/10.1101/2020.11.15.378125
Vitalii Kleshchevnikov
1Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
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Artem Shmatko
1Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
2Moscow State University, Leninskie Gory, Moscow, 119991, Russia
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Emma Dann
1Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
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Alexander Aivazidis
1Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
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Hamish W King
1Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
3Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London E1 2AT, UK
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Tong Li
1Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
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Artem Lomakin
4European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, UK
5European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg 69117, Germany
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Veronika Kedlian
1Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
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Mika Sarkin Jain
1Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
6Theory of Condensed Matter, Dept Physics, Cavendish Laboratory, University of Cambridge, JJ Thomson Ave, Cambridge CB3 0HE, UK
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Jun Sung Park
1Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
4European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, UK
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Lauma Ramona
1Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
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Elizabeth Tuck
1Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
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Anna Arutyunyan
1Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
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Roser Vento-Tormo
1Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
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Moritz Gerstung
4European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, UK
5European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg 69117, Germany
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Louisa James
3Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London E1 2AT, UK
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Oliver Stegle
1Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
5European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg 69117, Germany
7Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany
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  • For correspondence: ob5@sanger.ac.uk oliver.stegle@embl.de
Omer Ali Bayraktar
1Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
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  • ORCID record for Omer Ali Bayraktar
  • For correspondence: ob5@sanger.ac.uk oliver.stegle@embl.de
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Abstract

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 сell2location, 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 сell2location 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 сell2location 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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 17, 2020.
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Comprehensive mapping of tissue cell architecture via integrated single cell and spatial transcriptomics
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
bioRxiv 2020.11.15.378125; doi: https://doi.org/10.1101/2020.11.15.378125
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Comprehensive mapping of tissue cell architecture via integrated single cell and spatial transcriptomics
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
bioRxiv 2020.11.15.378125; doi: https://doi.org/10.1101/2020.11.15.378125

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