Recent advancements in spatial transcriptomics(ST)technologies allow researchers to simultaneously measure RNA expression levels for hundreds to thousands of genes while preserving spatial information within tissues,p...Recent advancements in spatial transcriptomics(ST)technologies allow researchers to simultaneously measure RNA expression levels for hundreds to thousands of genes while preserving spatial information within tissues,providing critical insights into spatial gene expression patterns,tissue organization,and gene functionality.However,existing methods for clustering spatially variable genes(SVGs)into co-expression modules often fail to detect rare or unique spatial expression patterns.To address this,we present spatial transcriptomics iterative hierarchical clustering(stIHC),a novel method for clustering SVGs into co-expression modules,representing groups of genes with shared spatial expression patterns.Through three simulations and applications to ST datasets from technologies such as 10x Visium,10x Xenium,and Spatial Transcriptomics,stIHC outperforms clustering approaches used by popular SVG detection methods,including SPARK,SPARK-X,MERINGUE,and SpatialDE.Gene ontology enrichment analysis confirms that genes within each module share consistent biological functions,supporting the functional relevance of spatial co-expression.Robust across technologies with varying gene numbers and spatial resolution,stIHC provides a powerful tool for decoding the spatial organization of gene expression and the functional structure of complex tissues.展开更多
The liver serves as a central organ regulating numerous complex metabolic processes[1,2].Hepatic lobule metabolic zonation supports distinct hepatocyte functions through spatially dependent gene expression that is gov...The liver serves as a central organ regulating numerous complex metabolic processes[1,2].Hepatic lobule metabolic zonation supports distinct hepatocyte functions through spatially dependent gene expression that is governed by intricate signaling networks and interactions with diverse non-parenchymal cells[3–5].Notably,liver sinusoidal endothelial cells(LSECs)provide critical regulatory functions during hepatic regeneration and pathological adaptation[6].However,current hepatic pathology research is limited by inadequate models that poorly replicate human disease phenotypes and pharmacological responses.展开更多
基金Science Foundation Ireland,Grant/Award Numbers:18/CRT/6214,18/CRT/6214(S4)。
文摘Recent advancements in spatial transcriptomics(ST)technologies allow researchers to simultaneously measure RNA expression levels for hundreds to thousands of genes while preserving spatial information within tissues,providing critical insights into spatial gene expression patterns,tissue organization,and gene functionality.However,existing methods for clustering spatially variable genes(SVGs)into co-expression modules often fail to detect rare or unique spatial expression patterns.To address this,we present spatial transcriptomics iterative hierarchical clustering(stIHC),a novel method for clustering SVGs into co-expression modules,representing groups of genes with shared spatial expression patterns.Through three simulations and applications to ST datasets from technologies such as 10x Visium,10x Xenium,and Spatial Transcriptomics,stIHC outperforms clustering approaches used by popular SVG detection methods,including SPARK,SPARK-X,MERINGUE,and SpatialDE.Gene ontology enrichment analysis confirms that genes within each module share consistent biological functions,supporting the functional relevance of spatial co-expression.Robust across technologies with varying gene numbers and spatial resolution,stIHC provides a powerful tool for decoding the spatial organization of gene expression and the functional structure of complex tissues.
基金supported in part by the National Key Research and Development Program of China(2022YFA1103400 and 2022YFC2406704)the National Natural Science Foundation of China(32371477,82090051,and 92168207).
文摘The liver serves as a central organ regulating numerous complex metabolic processes[1,2].Hepatic lobule metabolic zonation supports distinct hepatocyte functions through spatially dependent gene expression that is governed by intricate signaling networks and interactions with diverse non-parenchymal cells[3–5].Notably,liver sinusoidal endothelial cells(LSECs)provide critical regulatory functions during hepatic regeneration and pathological adaptation[6].However,current hepatic pathology research is limited by inadequate models that poorly replicate human disease phenotypes and pharmacological responses.
