Fig. 6: Recurrent micro-ecological modules characterize the spatial diversity of breast cancer ecosystem.

a Diagram for the identification of micro-ecological modules (MEMs). b Hierarchical clustering of spatial correlation matrix of tumor, inflammatory and stroma cell clusters identifies eight micro-ecological modules: i) Module1_TC, Module1 tumor core; ii) Module2_LT, Module2 loosely distributed tumor cells; iii) Module3_DI, Module3 discrete inflammatory cell infiltration; iv) Module4_TS, Module4 colocalization of tumor cells and stroma cells; v) Module5_LC, Module5 low cellularity; vi) Module6_SI, Module6 colocalization of stroma and inflammatory cells; vii) Module7_TSI, Module7 colocalization of tumor, stroma and inflammatory cells; viii) Module8_IA, Module8 local inflammatory cell aggregation. Rows and columns are ordered by hierarchical clustering. c Spatial patterns of MEMs based on Moran’s I statistics. d Heatmap of MEM scores of all spots. Spots (columns) are classified into the eight MEMs according to its maximum MEM score. Spots where all module scores are zero are classified as Module0_NC. e Thumbnail of a whole slide image with manually histological annotation (left) and with MEM mapping (right). In histological annotation, a pathologist manually delineated the regions of different histological patterns including two types of tumor regions (red and purple), stroma (blue), immune cell aggregation in stroma (green) and immune infiltration in tumor (yellow). Scale bar: 4 mm. f Composition of MEMs of different histological regions. g Mapping the spatial diversity of histological regions of immune infiltration, tumor and stroma based on MEMs. Scale bar: 200 μm. MEM micro-ecological module, ROI regions of interest.