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Screening cell-cell communication in spatial transcriptomics via collective optimal transport

View ORCID ProfileZixuan Cang, Yanxiang Zhao, Axel A. Almet, Adam Stabell, Raul Ramos, Maksim Plikus, Scott X. Atwood, Qing Nie
doi: https://doi.org/10.1101/2022.08.24.505185
Zixuan Cang
1Department of Mathematics and Center for Research in Scientific Computation, North Carolina State University, Raleigh, NC 27695, USA
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  • ORCID record for Zixuan Cang
Yanxiang Zhao
2Department of Mathematics, The George Washington University, Washington, DC 20052, USA
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Axel A. Almet
3Department of Mathematics, University of California, Irvine, CA 92697, USA
5The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA 92697, USA
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Adam Stabell
4Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA
5The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA 92697, USA
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Raul Ramos
4Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA
5The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA 92697, USA
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Maksim Plikus
4Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA
5The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA 92697, USA
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Scott X. Atwood
4Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA
5The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA 92697, USA
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Qing Nie
3Department of Mathematics, University of California, Irvine, CA 92697, USA
4Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA
5The NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA 92697, USA
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  • For correspondence: qnie@uci.edu
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Abstract

Spatial transcriptomic technologies and spatially annotated single cell RNA-sequencing (scRNA-seq) datasets provide unprecedented opportunities to dissect cell-cell communication (CCC). How to incorporate the spatial information and complex biochemical processes in reconstructing CCC remains a major challenge. Here we present COMMOT to infer CCC in spatial transcriptomics, which accounts for the competition among different ligand and receptor species as well as spatial distances between cells. A novel collective optimal transport method is developed to handle complex molecular interactions and spatial constraints. We introduce downstream analysis tools on spatial directionality of signalings and genes regulated by such signalings using machine learning models. We apply COMMOT to simulation data and eight spatial datasets acquired with five different technologies, showing its effectiveness and robustness in identifying spatial CCC in data with varying spatial resolutions and gene coverages. Finally, COMMOT reveals new CCCs during skin morphogenesis in a case study of human epidermal development. Both the method and the computational package have broad applications in inferring cell-cell interactions within spatial genomics datasets.

Competing Interest Statement

The authors have declared no competing interest.

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Posted August 26, 2022.
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Screening cell-cell communication in spatial transcriptomics via collective optimal transport
Zixuan Cang, Yanxiang Zhao, Axel A. Almet, Adam Stabell, Raul Ramos, Maksim Plikus, Scott X. Atwood, Qing Nie
bioRxiv 2022.08.24.505185; doi: https://doi.org/10.1101/2022.08.24.505185
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Screening cell-cell communication in spatial transcriptomics via collective optimal transport
Zixuan Cang, Yanxiang Zhao, Axel A. Almet, Adam Stabell, Raul Ramos, Maksim Plikus, Scott X. Atwood, Qing Nie
bioRxiv 2022.08.24.505185; doi: https://doi.org/10.1101/2022.08.24.505185

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