PHONEMeS (PHOsphorylation NEtworks for Mass Spectrometry) is a method to model signaling networks based on untargeted phosphoproteomics mass spectrometry data and kinase/phosphatase-substrate (K/P-S) interactions. This is a tool currently being developed by the saezlab members. The tool has been implemented as an R-package which contains the accompanying R functions as well as several examples about how to run a PHONEMeS analysis. The method was originally introduced from Terfve 2015.

Example network

Figure1: PHONEMeS pipeline.

Recently PHONEMeS has been has been reformulated as an Integer Linear Programming (PHONEMeS-ILP, Gjerga 2021) which is orders of magnitude faster than the original implementation, it requires no cluster infrastructure to run the analysis and expands the scenarios that can be analyzed (Figure 1).

Information about the various PHONEMeS variants implemented and usage details and pipeline can be found here.

Example network

Figure 2: Example of a time-resolved network model output from PHONEMeS for UACC257 cells. Figure from [Schafer 2019]( (licensed under the Creative Commons Attribution CC BY 4.0 ). EDNRB (green diamond) was connected to its target phosphorylation sites (red hexagons) through intermediary kinases or G proteins (blue circles) in a time‐resolved variant of the PHONEMeS approach. Central kinases, which were also identified by kinase activation prediction, are shown as intermediary kinases with dark blue shading. Edge thickness corresponds to weights, which were assigned by downsampling the network 100 times.


If you use any of the ILP implementations of PHONEMeS (PHONEMeS-ILP/PHONEMeS-mult/PHONEMeS-UD), please cite:

Gjerga E., Dugourd A., Tobalina L., Sousa A., Saez-Rodriguez J. (2021). PHONEMeS: Efficient Modeling of Signaling Networks Derived from Large-Scale Mass-Spectrometry Data J Prot Res, 2021, DOI: 10.1021/acs.jproteome.0c00958.

If you use the original implementation of PHONEMeS or if you would like to make mention of the tool, please additionally cite:

Terfve C. D. A., Wilkes E. H., Casado P., Cutillas P. R., and Saez-Rodriguez J. (2015). Large-scale models of signal propagation in human cells derived from discovery phosphoproteomic data. Nature Communications, 6:8033.

Other References