Tools for the detection and network contextualisation of protein methylation

Tay A, Pang CNI, Winter DL, Hart-Smith G, Hamey J and Wilkins MR

School of Biotechnology and Biomolecular Sciences, University of New South Wales.

Protein methylation has recently emerged as one of the most widespread post-translational modifications of proteins in the eukaryotic cell. Its detection by mass spectrometry, however, is affected by high false discovery rates. Functionally, it is poorly understood yet it is known to modulate many protein-protein interactions and, in some cases, can interplay with other modifications. Here we describe two new tools that assist with the identification of methylated peptides from tandem mass spectrometry analyses (MS2 Deisotoper, MethylQuant). The first increases peptide identification rates through the deisotoping of fragmentation spectra, whereas the second takes advantages of heavy isotopic labelling (methyl-SILAC) to unequivocally identify sites of protein methylation. We also describe a new Cytoscape app (PTMoracle). This facilitates the contextualisation of methylation in protein interaction networks, with structural data associated with protein-protein interactions and with all other known post-translational modifications. Case studies will be given to illustrate the utility of these tools.