Quantitative characterization of cell niches in spatially resolved omics data

• Published in: Nature genetics Vol. 57; no. 4; pp. 897 - 909
• Main Authors: Birk, Sebastian, Bonafonte-Pardàs, Irene, Feriz, Adib Miraki, Boxall, Adam, Agirre, Eneritz, Memi, Fani, Maguza, Anna, Yadav, Anamika, Armingol, Erick, Fan, Rong, Castelo-Branco, Gonçalo, Theis, Fabian J., Bayraktar, Omer Ali, Talavera-López, Carlos, Lotfollahi, Mohammad
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2025
• Subjects: 14/63; 38/91; 631/114/2164; 631/114/794; 631/1647/2017; 631/1647/48; 631/337/2019; Agriculture; Animal Genetics and Genomics; Animals; Biomedical and Life Sciences; Biomedicine; Brain - embryology; Brain - metabolism; Cancer Research; Cell Communication - genetics; Computational Biology - methods; Deep Learning; Embryonic Development - genetics; Gene Function; Genomics - methods; Human Genetics; Humans; Mice; Neoplasms - genetics; Neoplasms - pathology; Signal Transduction - genetics; Tumor Microenvironment
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/s41588-025-02120-6

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. NicheCompass is a graph variational autoencoder approach for identifying cellular niches defined by cell–cell communication and other interactions, applicable to a broad variety of spatial multi-omic data.