FLOW: maximum flow framework for the identification of factors mediating the signaling convergence of multiple receptors

Abstract

MotivationCell-cell crosstalk involves simultaneous interactions of multiple receptors and ligands, followed by downstream signaling cascades working through receptors converging at dominant transcription factors which then integrate and propagate multiple signals into a cellular response. Single-cell RNAseq of multiple cell subsets isolated from a defined microenvironment provides us with a unique opportunity to learn about such interactions reflected in their gene expression levels.ResultsWe developed the FLOW framework with the intention of mapping the potential ligand-receptor interactions between different cell subsets based on a maximum flow computation in a network of protein-protein interactions (PPIs). The maximum flow approach further allows characterizing the intracellular downstream signal transduction from differentially expressed receptors towards dominant transcription factors. This, therefore enables the association between a set of receptors and their downstream activated pathways. Importantly, we were able to identify key transcription factors toward which the convergence of signaling of multiple receptors occurs. These identified factors have a unique role in the integration and propagation of signaling following cell-cell interactions.

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Navigating the landscapes of spatial transcriptomics: How computational methods guide the way

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