mUSP: a high-accuracy map of the in situ crosstalk of ubiquitylation and SUMOylation proteome predicted via the feature enhancement approach.

Reversible post-translational modification (PTM) orchestrates various biological processes by changing the properties of proteins. Since many proteins are multiply modified by PTMs, identification of PTM crosstalk site has emerged to be an intriguing topic and attracted much attention. In this study, we systematically deciphered the in situ crosstalk of ubiquitylation and SUMOylation that co-occurs on the same lysine residue. We first collected 3363 ubiquitylation-SUMOylation (UBS) crosstalk site on 1302 proteins and then investigated the prime sequence motifs, the local evolutionary degree and the distribution of structural annotations at the residue and sequence levels between the UBS crosstalk and the single modification sites. Given the properties of UBS crosstalk sites, we thus developed the mUSP classifier to predict UBS crosstalk site by integrating different types of features with two-step feature optimization by recursive feature elimination approach. By using various cross-validations, the mUSP model achieved an average area under the curve (AUC) value of 0.8416, indicating its promising accuracy and robustness. By comparison, the mUSP has significantly better performance with the improvement of 38.41 and 51.48% AUC values compared to the cross-results by the previous single predictor. The mUSP was implemented as a web server available at http://bioinfo.ncu.edu.cn/mUSP/index.html to facilitate the query of our high-accuracy UBS crosstalk results for experimental design and validation.