Fig. 2: Community ecology-inspired niches offer a quantitative framework to interpret cellular tissue architecture from multiplex histology data.

a MIBI identifies the position and the type of cells in tumor sections. Shown is sample 5 from Keren et al. b Co-variance structure emerges when considering the cellular composition of sampling sites 25 μm in size or larger. c Representing the cellular composition of sites on three axes (PCs) reveals that site cellular composition does not form clusters but instead describes a continuum constrained by a 3D simplex. P-value: t-ratio test, n = 4000 sampling sites, one-sided. d The finding that site cellular composition is constrained by a 3D simplex suggests a view of tumor architecture in which local cellular composition is a weighted average of four histological niches, the endpoints of the simplex. Sites located close to an endpoint localize at the core of the niche while sites at the interface between niches fall on the edges of the simplex. e Coloring tissue sections according to the local weight of the four niches segments tissue sections into niches. Spatial variations in local cellular composition can be interpreted as space-dependent changes in the weight of the four niches. Colors: local niche weight, as in c–d. f Cells located at interface regions—here the inflammation × cancer interface—are automatically identified as cells where the product of the weights of the inflammation and cancer niches is high. g The cellular composition of each niche has a histo-pathological interpretation: cancer, fibrotic/necrotic, inflammatory, and tertiary lymphoid structure (TLS). h Community ecology-inspired niches capture tissue cellular architecture more concisely than clustering-based niches. i. Community ecology-inspired niches can address artifacts of clustering-based niches. j. The same four niches explain both intra-tumor- and inter-patient-variation in the cellular composition of tumors. k Niches generalize across breast cancer types and explain inter-patient variation in the macroscopic cellular composition of tumors. DC dendritic cell, Neu neutrophil, Mono monocyte, NK natural killer. Source data are provided as a Source Data file.