PhosphoPath: Visualization of Phosphosite-centric Dynamics in Temporal Molecular Networks

Protein phosphorylation is an essential post-translational modification (PTM) regulating many biological processes at the cellular and multicellular level. Continuous improvements in phosphoproteomics technology allow the analysis of this PTM in an expanding biological content. Yet, up till now proteome data visualization tools are still very gene centric, hampering the ability to comprehensively map and study PTM dynamics. Here we present PhosphoPath, a Cytoscape app designed for the visualization and analysis of quantitative proteome and phosphoproteome datasets. PhosphoPath brings knowledge into the biological network by importing publically available data, and enables PTM site-specific visualization of information from quantitative time series. To showcase PhosphoPath performance we use a quantitative proteomics dataset comparing patient derived melanoma cell lines grown either in conventional cell culture or xenografts.

PhosphoPath: Visualization of phosphosite-centric dynamics in temporal molecular networks

Raaijmakers LM, Giansanti P, Possik PA, Mueller J, Peeper DS, Heck AJ, Altelaar AF.
J Proteome Res. 2015 Oct 2;14(10):4332-4341
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Deep proteome profiling of Trichoplax adhaerens reveals remarkable features at the origin of metazoan multicellularity.

Genome sequencing of arguably the simplest known animal, Trichoplax adhaerens, uncovered a rich array of transcription factor and signalling pathway genes. Although the existence of such genes allows speculation about the presence of complex regulatory events, it does not reveal the level of actual protein expression and functionalization through posttranslational modifications. Using high-resolution mass spectrometry, we here semi-quantify 6,516 predicted proteins, revealing evidence of horizontal gene transfer and the presence at the protein level of nodes important in animal signalling pathways. Moreover, our data demonstrate a remarkably high activity of tyrosine phosphorylation, in line with the hypothesized burst of tyrosine-regulated signalling at the instance of animal multicellularity. Together, this Trichoplax proteomics data set offers significant new insight into the mechanisms underlying the emergence of metazoan multicellularity and provides a resource for interested researchers.
Ringrose JH, van den Toorn HW, Eitel M, Post H, Neerincx P, Schierwater B, Altelaar AF, Heck AJ.
Nat Commun. 2013;4:1408.