Extended Data Fig. 6: Spatial organization of the tumor microenvironment.

a. OVCA NYU1 H&E image with spots colored by annotation (scale bar represents 1 mm). b-c. Joint dimensionality reduction after mutual nearest neighbor integration (MNN) of single-cell and ST spots for the OVCA NYU1 sample, with (b) single-cell transcriptomes in gray and ST spots colored according to their annotation and (c) spots in gray and single-cell transcriptomes colored by their annotated cell type. The single cells form clusters at the periphery, indicating distinct cell types. The ST spots are either mixed with individual single-cell clusters, indicating a pure population, or bridge multiple clusters, indicating a combination of cell types. Specifically, ‘Malignant’ spots are mixed with the malignant cell cluster, ‘Normal’ spots are in the region of nonmalignant cell types, and ‘Both’ spots span both malignant and nonmalignant single-cell clusters. d. LIHC NYU1 H&E image with spots colored by annotation as in a. (scale bar represents 1 mm). e-g. Joint dimensionality reduction of single-cell and ST spots for the LIHC NYU1 sample, with (e) single-cell transcriptomes in gray and ST spots colored according to their annotation, (f) spots in gray and single-cell transcriptomes colored by their annotated cell type and (g) spots colored according to their coordinate along the x-axis. This sample has two spatially distinct tumor nodules, with the left having substantial mixing between malignant and nonmalignant cells and the right consisting almost exclusively of malignant cells. The joint dimensionality reduction analysis reflects the two corresponding malignant clusters, which were not distinct when considering the single-cell dimensionality reduction alone.