Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity

Abstract Advances in single-cell technology have enabled molecular dissection of heterogeneous biospecimens at unprecedented scales and resolutions. Cluster-centric approaches are widely applied in analyzing single-cell data, however they have limited power in dissecting and interpreting highly hete...

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Main Authors: Qingnan Liang, Yuefan Huang, Shan He, Ken Chen
Format: Article
Language:English
Published: Nature Portfolio 2023-12-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-44206-x
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author Qingnan Liang
Yuefan Huang
Shan He
Ken Chen
author_facet Qingnan Liang
Yuefan Huang
Shan He
Ken Chen
author_sort Qingnan Liang
collection DOAJ
description Abstract Advances in single-cell technology have enabled molecular dissection of heterogeneous biospecimens at unprecedented scales and resolutions. Cluster-centric approaches are widely applied in analyzing single-cell data, however they have limited power in dissecting and interpreting highly heterogenous, dynamically evolving data. Here, we present GSDensity, a graph-modeling approach that allows users to obtain pathway-centric interpretation and dissection of single-cell and spatial transcriptomics (ST) data without performing clustering. Using pathway gene sets, we show that GSDensity can accurately detect biologically distinct cells and reveal novel cell-pathway associations ignored by existing methods. Moreover, GSDensity, combined with trajectory analysis can identify curated pathways that are active at various stages of mouse brain development. Finally, GSDensity can identify spatially relevant pathways in mouse brains and human tumors including those following high-order organizational patterns in the ST data. Particularly, we create a pan-cancer ST map revealing spatially relevant and recurrently active pathways across six different tumor types.
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spelling doaj.art-fb2a588565874c8da9a256fede687c772023-12-24T12:22:56ZengNature PortfolioNature Communications2041-17232023-12-0114111710.1038/s41467-023-44206-xPathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensityQingnan Liang0Yuefan Huang1Shan He2Ken Chen3Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer CenterDepartment of Bioinformatics and Computational Biology, UT MD Anderson Cancer CenterDepartment of Bioinformatics and Computational Biology, UT MD Anderson Cancer CenterDepartment of Bioinformatics and Computational Biology, UT MD Anderson Cancer CenterAbstract Advances in single-cell technology have enabled molecular dissection of heterogeneous biospecimens at unprecedented scales and resolutions. Cluster-centric approaches are widely applied in analyzing single-cell data, however they have limited power in dissecting and interpreting highly heterogenous, dynamically evolving data. Here, we present GSDensity, a graph-modeling approach that allows users to obtain pathway-centric interpretation and dissection of single-cell and spatial transcriptomics (ST) data without performing clustering. Using pathway gene sets, we show that GSDensity can accurately detect biologically distinct cells and reveal novel cell-pathway associations ignored by existing methods. Moreover, GSDensity, combined with trajectory analysis can identify curated pathways that are active at various stages of mouse brain development. Finally, GSDensity can identify spatially relevant pathways in mouse brains and human tumors including those following high-order organizational patterns in the ST data. Particularly, we create a pan-cancer ST map revealing spatially relevant and recurrently active pathways across six different tumor types.https://doi.org/10.1038/s41467-023-44206-x
spellingShingle Qingnan Liang
Yuefan Huang
Shan He
Ken Chen
Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity
Nature Communications
title Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity
title_full Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity
title_fullStr Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity
title_full_unstemmed Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity
title_short Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity
title_sort pathway centric analysis for single cell rna seq and spatial transcriptomics data with gsdensity
url https://doi.org/10.1038/s41467-023-44206-x
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AT kenchen pathwaycentricanalysisforsinglecellrnaseqandspatialtranscriptomicsdatawithgsdensity