Statistical identification of cell type-specific spatially variable genes in spatial transcriptomics

Abstract An essential task in spatial transcriptomics is identifying spatially variable genes (SVGs). Here, we present Celina, a statistical method for systematically detecting cell type-specific SVGs (ct-SVGs)—a subset of SVGs exhibiting distinct spatial expression patterns within specific cell typ...

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Main Authors: Lulu Shang, Peijun Wu, Xiang Zhou
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56280-4
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author Lulu Shang
Peijun Wu
Xiang Zhou
author_facet Lulu Shang
Peijun Wu
Xiang Zhou
author_sort Lulu Shang
collection DOAJ
description Abstract An essential task in spatial transcriptomics is identifying spatially variable genes (SVGs). Here, we present Celina, a statistical method for systematically detecting cell type-specific SVGs (ct-SVGs)—a subset of SVGs exhibiting distinct spatial expression patterns within specific cell types. Celina utilizes a spatially varying coefficient model to accurately capture each gene’s spatial expression pattern in relation to the distribution of cell types across tissue locations, ensuring effective type I error control and high power. Celina proves powerful compared to existing methods in single-cell resolution spatial transcriptomics and stands as the only effective solution for spot-resolution spatial transcriptomics. Applied to five real datasets, Celina uncovers ct-SVGs associated with tumor progression and patient survival in lung cancer, identifies metagenes with unique spatial patterns linked to cell proliferation and immune response in kidney cancer, and detects genes preferentially expressed near amyloid-β plaques in an Alzheimer’s model.
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issn 2041-1723
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spelling doaj-art-8202caba33414ff99fcd7ac80ef828162025-02-02T12:31:24ZengNature PortfolioNature Communications2041-17232025-01-0116112010.1038/s41467-025-56280-4Statistical identification of cell type-specific spatially variable genes in spatial transcriptomicsLulu Shang0Peijun Wu1Xiang Zhou2Department of Biostatistics, The University of Texas MD Anderson Cancer CenterDepartment of Biostatistics, University of MichiganDepartment of Biostatistics, University of MichiganAbstract An essential task in spatial transcriptomics is identifying spatially variable genes (SVGs). Here, we present Celina, a statistical method for systematically detecting cell type-specific SVGs (ct-SVGs)—a subset of SVGs exhibiting distinct spatial expression patterns within specific cell types. Celina utilizes a spatially varying coefficient model to accurately capture each gene’s spatial expression pattern in relation to the distribution of cell types across tissue locations, ensuring effective type I error control and high power. Celina proves powerful compared to existing methods in single-cell resolution spatial transcriptomics and stands as the only effective solution for spot-resolution spatial transcriptomics. Applied to five real datasets, Celina uncovers ct-SVGs associated with tumor progression and patient survival in lung cancer, identifies metagenes with unique spatial patterns linked to cell proliferation and immune response in kidney cancer, and detects genes preferentially expressed near amyloid-β plaques in an Alzheimer’s model.https://doi.org/10.1038/s41467-025-56280-4
spellingShingle Lulu Shang
Peijun Wu
Xiang Zhou
Statistical identification of cell type-specific spatially variable genes in spatial transcriptomics
Nature Communications
title Statistical identification of cell type-specific spatially variable genes in spatial transcriptomics
title_full Statistical identification of cell type-specific spatially variable genes in spatial transcriptomics
title_fullStr Statistical identification of cell type-specific spatially variable genes in spatial transcriptomics
title_full_unstemmed Statistical identification of cell type-specific spatially variable genes in spatial transcriptomics
title_short Statistical identification of cell type-specific spatially variable genes in spatial transcriptomics
title_sort statistical identification of cell type specific spatially variable genes in spatial transcriptomics
url https://doi.org/10.1038/s41467-025-56280-4
work_keys_str_mv AT lulushang statisticalidentificationofcelltypespecificspatiallyvariablegenesinspatialtranscriptomics
AT peijunwu statisticalidentificationofcelltypespecificspatiallyvariablegenesinspatialtranscriptomics
AT xiangzhou statisticalidentificationofcelltypespecificspatiallyvariablegenesinspatialtranscriptomics