Spatial domain analysis to estimate spatiotemporal pathological mechanisms in microenvironment with single-cell spatial omics data

Single-cell spatial omics analysis requires consideration of biological functions and mechanisms in a microenvironment. However, microenvironment analysis using bioinformatic methods is limited by the need to detect histological morphology. In this study, we developed SpatialKNife (SKNY), an image-processing-based toolkit that detects spatial domains that potentially reflect histology and extends these domains to the microenvironment. The SKNY algorithm identified tumour spatial domains from spatial transcriptomic data of breast cancer, followed by clustering of these domains, trajectory estimation, and spatial extension to the tumour microenvironment (TME). The results of the trajectory estimation were consistent with the known mechanisms of cancer progression. We observed endothelial cell and macrophage infiltration into the TME at mid-stage progression. Our results suggest that analysis using the spatial domain as a unit reflects pathological mechanisms in the TME. This approach may be applicable to the biological estimation of diverse microenvironments.