Nature Genetics · 2025 · 63 citations · 96 references
Life SciencesBioinformaticsCell BiologyCell SignalingComputational BiologyTumor MicroenvironmentCancer Cell SignalingCancer Cell-cell CommunicationCell-cell Communication AnalysisSpatial Multi-omics IntegrationSpatial Single-cell AnalysisSpatial Systems BiologyGene Expression AtlasesReference Atlas ConstructionReference MappingSpatial Cell Atlas ConstructionSpatial Cell-cell CommunicationSpatial Multi-omics AnalysisSpatial Reference MappingTumor Microenvironment Mapping
Spatial omics enable the characterization of colocalized cell communities that coordinate specific functions within tissues. These communities, or niches, are shaped by interactions between neighboring cells, yet existing computational methods rarely leverage such interactions for their identification and characterization. To address this gap, here we introduce NicheCompass, a graph deep-learning method that models cellular communication to learn interpretable cell embeddings that encode signaling events, enabling the identification of niches and their underlying processes. Unlike existing methods, NicheCompass quantitatively characterizes niches based on communication pathways and consistently outperforms alternatives. We show its versatility by mapping tissue architecture during mouse embryonic development and delineating tumor niches in human cancers, including a spatial reference mapping application. Finally, we extend its capabilities to spatial multi-omics, demonstrate cross-technology integration with datasets from different sequencing platforms and construct a whole mouse brain spatial atlas comprising 8.4 million cells, highlighting NicheCompass' scalability. Overall, NicheCompass provides a scalable framework for identifying and analyzing niches through signaling events.
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