TrimNN: Characterizing cellular community motifs for studying multicellular topological organization in complex...

The spatial arrangement of cells plays a pivotal role in shaping tissue functions in various biological systems and diseased microenvironments. However, it is still under-investigated of the topological coordinating rules among different cell types as tissue spatial patterns. Here, we introduce the Triangulation cellular community motif Neural Network (TrimNN), a bottom-up approach to estimate the prevalence of sizeable conservative cell organization patterns as Cellular Community (CC) motifs in spatial transcriptomics and proteomics. Different from clustering cell type composition from classical top-down analysis, TrimNN differentiates cellular niches as countable topological blocks in recurring interconnections of various types, representing multicellular neighborhoods with interpretability and generalizability. This graph-based deep learning framework adopts inductive bias in CCs and uses a semi-divide and conquer approach in the triangulated space. In spatial omics studies, various sizes of CC motifs identified by TrimNN robustly reveal relations between spatially distributed cell-type patterns and diverse phenotypical biological functions.