Systems-level reconstruction of kinase phosphosignaling networks regulating endothelial barrier integrity using temporal data

Ling Wei,J. Aitchison,A. Kaushansky,Fred D. Mast

Published 2024 in bioRxiv

ABSTRACT

Phosphosignaling networks control cellular processes. We built kinase-mediated regulatory networks elicited by thrombin stimulation of brain endothelial cells using two computational strategies: Temporal Pathway Synthesizer (TPS), which uses phosphoproteomics data as input, and Temporally REsolved KInase Network Generation (TREKING), which uses kinase inhibitor screens. TPS and TREKING predicted overlapping barrier-regulatory kinases connected with unique network topology. Each strategy effectively describes regulatory signaling networks and is broadly applicable across biological systems.

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