Microenvironment-aware spatial modeling for accurate inference of cell identity

Date:	January 5, 2026
PMID:	PMC12774649
Category:	N/A
Authors:	Qi Liu, Yu Wang, Chih-Yuan Hsu, Celestine N Wanjalla, Ken S Lau, Yu Shyr
DOI:	10.1093/nar/gkaf1477

Spatial omics technologies enable the simultaneous measurement of molecular features within their spatial context, providing unprecedented insights into cellular organization and tissue architecture. The advent of single-cell resolution platforms has further enhanced our ability to uncover microenvironment-dependent cell states. While numerous computational methods have been developed for spatial omics analysis, most focus on spatial domain detection rather than on resolving cell identities. Traditional single-cell clustering methods rely solely on intrinsic molecular features to determine cell identities, missing the impact of the local microenvironment on cell states. To address this gap, we present MEcell, a parameter-free method that explicitly incorporates spatial context and automatically adjusts its contribution to improve cell identity modeling. Applied to 90 simulated and 7 real datasets spanning multiple spatial transcriptomics platforms and tissue types, including MERFISH/Vizgen, Xenium, CosMx, Visium HD, Slide-seqV2, and open-ST, MEcell consistently outperformed existing methods in accurately inferring cell identities. These results highlight the critical role of microenvironment in defining cell identity and demonstrate the power of MEcell for capturing spatially informed cellular heterogeneity.

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Acknowledgements:

The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, or the National Institute of Health.

The Translational and Basic Science Research in Early Lesions (TBEL) Research Consortia is supported and funded by grants from the National Cancer Institute and the National Institutes of Health under the following award numbers:

Project Number:	Awardee Organization
U54CA274374	Fred Hutchinson Cancer Center
U54CA274375	Houston Methodist Research Institute
U54CA274370	Johns Hopkins University
U54CA274371	UT MD Anderson Cancer Center
U54CA274367	Vanderbilt University Medical Center