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

Ron Sheinin, Koren Salomon, Eilam Yeini, Shai Dulberg, Ayelet Kaminitz, Ronit Satchi-Fainaro, Roded Sharan, Asaf Madi

Research output: Contribution to journalArticlepeer-review

Abstract

Cell-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. We developed the interFLOW framework to map 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 characterization of the intracellular downstream signal transduction from differentially expressed receptors towards dominant transcription factors, therefore, enabling 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 multiple receptor signaling pathways occurs. These identified factors have a unique role in the integration and propagation of signaling following specific cell-cell interactions.

Original languageEnglish
Article number66
Journalnpj Systems Biology and Applications
Volume10
Issue number1
DOIs
StatePublished - Dec 2024

All Science Journal Classification (ASJC) codes

  • Modelling and Simulation
  • General Biochemistry,Genetics and Molecular Biology
  • Drug Discovery
  • Computer Science Applications
  • Applied Mathematics

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