phuEGO: A network-based method to reconstruct active signalling pathways from phosphoproteomics datasets

Mol Cell Proteomics. 2024 Apr 18:100771. doi: 10.1016/j.mcpro.2024.100771. Online ahead of print.ABSTRACTSignalling networks are critical for virtually all cell functions. Our current knowledge of cell signalling has been summarised in signalling pathway databases, which, while useful, are highly biassed towards well-studied processes, and do not capture context specific network wiring or pathway cross-talk. Mass spectrometry-based phosphoproteomics data can provide a more unbiased view of active cell signalling processes in a given context, however, it suffers from low signal-to-noise ratio and poor reproducibility across experiments. While progress in methods to extract active signalling signatures from such data has been made, there are still limitations with respect to balancing bias and interpretability. Here we present phuEGO, which combines up-to-three-layer network propagation with ego network decomposition to provide small networks comprising active functional signalling modules. PhuEGO boosts the signal-to-noise ratio from global phosphoproteomics datasets, enriches the resulting networks for functional phosphosites and allows the improved comparison and integration across datasets. We applied phuEGO to five phosphoproteomics data sets from cell lines collected upon infection with SARS CoV2. PhuEGO was better able to identify common active functions across datasets and to point to a subnetwork enriched for known COVID-19 targets. Overall, phuEGO provides a flexible ...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Source Type: research