SpaFlow depicts the dynamics of ligand-receptor interaction in spatial transcriptomics data

Abstract

Spatial transcriptomics (ST) enables the study of cell-cell communication in native tissue context, but current methods for the ligand-receptor interaction (LRI) inference generally rely on static, distance-based assumptions. Here we present SpaFlow, a reaction-diffusion framework that models ligand diffusion, binding, dissociation, production and degradation to infer spatially resolved LRI activity and hotspots from ST data. Across paired 10x Visium and CosMx metastatic renal cell carcinoma datasets, SpaFlow outperformed existing methods in recovering spatially coherent LRIs, with inferred LRI activity showing stronger association with downstream signaling. In hepatocellular carcinoma after neoadjuvant immunotherapy, SpaFlow identified CXCL12-CXCR4 hotspots enriched at immune-rich tumor boundaries in responders. In aging mouse heart, SpaFlow resolved niche-specific pro-fibrotic and senescence-associated signaling, highlighting Postn-Itgav/Itgb5 as an additional pro-fibrotic axis and Angptl2-Pirb as a candidate mediator of inter-niche senescence-related communication. In human idiopathic pulmonary fibrosis lung, SpaFlow localized CXCL12-CXCR4 signaling between adventitial fibroblasts and CD4 T cells, CD8 T cells, and B cells in the fibrotic surrounding regions. Together, SpaFlow provides a physically informed framework for quantifying spatially constrained cell-cell communication and mechanistically interpreting signaling patterns in complex tissues.