Systematic Characterization and Prediction of Post-Translational Modification Cross-Talk

Yuanhua Huang, Bosen Xu, Xueya Zhou, Ying Li, Ming Lu, Rui Jiang, Tingting Li
2015 Molecular & Cellular Proteomics  
Post-translational modification (PTM) 1 plays an important role in regulating the functions of proteins. PTMs of multiple residues on one protein may work together to determine a functional outcome, which is known as PTM crosstalk. Identification of PTM cross-talks is an emerging theme in proteomics and has elicited great interest, but their properties remain to be systematically characterized. To this end, we collected 193 PTM cross-talk pairs in 77 human proteins from the literature and then
more » ... ested location preference and co-evolution at the residue and modification levels. We found that cross-talk events preferentially occurred among nearby PTM sites, especially in disordered protein regions, and cross-talk pairs tended to co-evolve. Given the properties of PTM cross-talk pairs, a naïve Bayes classifier integrating different features was built to predict cross-talks for pairwise combination of PTM sites. By using a 10-fold cross-validation, the integrated prediction model showed an area under the receiver operating characteristic (ROC) curve of 0.833, superior to using any individual feature alone. The prediction performance was also demonstrated to be robust to the biases in the collected PTM cross-talk pairs. The inte-grated approach has the potential for large-scale prioritization of PTM cross-talk candidates for functional validation and was implemented as a web server available at
doi:10.1074/mcp.m114.037994 pmid:25605461 pmcid:PMC4349993 fatcat:hw5jfqodf5ajdposyefedvx2vy