In multicellular organisms, cell identity and functions are primed and refined through interactions with other surrounding cells. Here, we propose a scalable machine learning method, termed SPRUCE, which is designed to systematically ascertain common cell-cell communication patterns embedded in single-cell RNA-seq data. We applied our approach to investigate tumor microenvironments consolidating multiple breast cancer datasets and found seven frequently observed interaction signatures and underlying gene-gene interaction networks. Our results implicate that a part of tumor heterogeneity, especially within the same subtype, is better understood by differential interaction patterns rather than the static expression of known marker genes.
