Quantitative phosphoproteomics-based molecular network description for high-resolution kinase-substrate interactome analysis
Motivation: Phosphorylation-dependent cellular signaling is known to play a diverse role in regulating multiple cellular processes such as proliferation, differentiation and apoptosis. Recent technological advances in mass spectrometry-based phosphoproteomics have enabled us to measure network-wide signaling dynamics in a comprehensive and quantitative manner. As conventional protein-protein interaction (PPI) information-based network analysis is insufficient to systematically analyze
... ation site-dependent complex interaction dynamics, here we develop and evaluate a platform to provide a high-resolution molecular network description for kinase-substrate interactome analysis. Results: In this study, we developed a Cytoscape-based bioinformatical platform named 'Post Translational Modification mapper (PTMapper)' to integrate PPI data with publicly available kinasesubstrate relations at the resolution of phosphorylated amino acid residues. The previous phosphoproteome data on EGF-induced cellular signaling in glioblastoma stem cells was applied to evaluate our platform, leading to discovery of phosphorylation-dependent crucial signaling modulation in the p70S6K1-related pathway. Our study revealed that high-resolution cellular network description of phosphorylation-site dependent kinase-substrate signaling regulation should accelerate phosphoproteomics-based exploration of novel drug targets in the context of each diseaserelated signaling. Availability and Implementation: PTMapper and the example data for construction of phosphorylation site-oriented networks are available at https://github.com/y-narushima/PTMapper.