Reference-based cell type matching of spatial transcriptomics data
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Abstract With the advent of multiplex fluorescence in situ hybridization (FISH) and in situ RNA sequencing technologies, spatial transcriptomics analysis is advancing rapidly. Spatial transcriptomics provides spatial location and pattern information about cells in tissue sections at single cell resolution. Cell type classification of spatially-resolved cells can also be inferred by matching the spatial transcriptomics data to reference single cell RNA-sequencing (scRNA-seq) data with cell types determined by their gene expression profiles. However, robust cell type matching of the spatial cells is challenging due to the intrinsic differences in resolution between the spatial and scRNA-seq data. In this study, we systematically evaluated six computational algorithms for cell type matching across four spatial transcriptomics experimental protocols (MERFISH, smFISH, BaristaSeq, and ExSeq) conducted on the same mouse primary visual cortex (VISp) brain region. We find that while matching results of individual algorithms vary to some degree, they also show agreement to some extent. We present two ensembl meta-analysis strategies to combine the individual matching results and share the consensus matching results in the Cytosplore Viewer ( https://viewer.cytosplore.org ) for interactive visualization and data exploration. The consensus matching can also guide spot-based spatial data analysis using SSAM, allowing segmentation-free cell type assignment.
Authors 18
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Affiliation as printed
J. Craig Venter Institute
J. Craig Venter Institute, La Jolla, CA, USA
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Allen Institute for Brain Science
Affiliation as printed
Allen Institute for Brain Science
Allen Institute for Brain Science, Seattle, WA, USA
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Affiliation as printed
School of Biomedical Convergence Engineering, Pusan National University
School of Biomedical Convergence Engineering, Pusan National University, Korea
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Leiden University Medical Center · Delft University of Technology
Affiliation as printed
LKEB, Dept of Radiology, Leiden University Medical Center
Pattern Recognition and Bioinformatics group, Delft University of Technology
LKEB, Dept of Radiology, Leiden University Medical Center, Leiden, the Netherlands
Pattern Recognition and Bioinformatics group, Delft University of Technology, Delft, The Netherlands
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Allen Institute for Brain Science
Affiliation as printed
Allen Institute for Brain Science
Allen Institute for Brain Science, Seattle, WA, USA
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Leiden University Medical Center · Delft University of Technology
Affiliation as printed
LKEB, Dept of Radiology, Leiden University Medical Center
Pattern Recognition and Bioinformatics group, Delft University of Technology
LKEB, Dept of Radiology, Leiden University Medical Center, Leiden, the Netherlands
Pattern Recognition and Bioinformatics group, Delft University of Technology, Delft, The Netherlands
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Affiliation as printed
J. Craig Venter Institute
J. Craig Venter Institute, La Jolla, CA, USA
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Affiliation as printed
Broad Institute of MIT and Harvard
Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Affiliation as printed
Broad Institute of MIT and Harvard
Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Leiden University Medical Center
Affiliation as printed
LKEB, Dept of Radiology, Leiden University Medical Center
LKEB, Dept of Radiology, Leiden University Medical Center, Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
LKEB, Dept of Radiology, Leiden University Medical Center
LKEB, Dept of Radiology, Leiden University Medical Center, Leiden, the Netherlands
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Stockholm University · Science for Life Laboratory
Affiliation as printed
Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University
Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
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University of Copenhagen · Harvard University
Affiliation as printed
Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen
Department of Biomedical Informatics, Harvard Medical School
Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
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Affiliation as printed
Broad Institute of MIT and Harvard
Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Affiliation as printed
Broad Institute of MIT and Harvard
Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Allen Institute for Brain Science
Affiliation as printed
Allen Institute for Brain Science
Allen Institute for Brain Science, Seattle, WA, USA
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Allen Institute for Brain Science
Affiliation as printed
Allen Institute for Brain Science
Allen Institute for Brain Science, Seattle, WA, USA
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Richard H. Scheuermann corresponding
J. Craig Venter Institute · La Jolla Institute for Immunology · University of California System · University of California San Diego
Affiliation as printed
Department of Pathology, University of California
Division of Vaccine Discovery, La Jolla Institute for Immunology
J. Craig Venter Institute
Department of Pathology, University of California, San Diego, CA, USA
Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, USA
J. Craig Venter Institute, La Jolla, CA, USA
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