Computational Prediction of Ubiquitination Proteins Using Evolutionary Profiles and Functional Domain Annotation

Ubiquitination, as a post-translational modification, is a crucial biological process in cell signaling, apoptosis, and localization. Identification of ubiquitination proteins is of fundamental importance for understanding the molecular mechanisms in biological systems and diseases. Although high-throughput experimental studies using mass spectrometry have identified many ubiquitination proteins and ubiquitination sites, the vast majority of ubiquitination proteins remain undiscovered, even in well-studied model organisms.To reduce experimental costs, computational methods have been introduced to predict ubiquitination sites, but the accuracy is unsatisfactory. If it can be predicted whether a protein can be ubiquitinated or not, it will help in predicting ubiquitination sites. However, all the computational methods so far can only predict ubiquitination sites.In this study, the first computational method for predicting ubiquitination proteins without relying on ubiquitination site prediction has been developed. The method extracts features from sequence conservation information through a grey system model, as well as functional domain annotation and subcellular localization.Together with the feature analysis and application of the relief feature selection algorithm, the results of 5-fold cross-validation on three datasets achieved a high accuracy of 90.13%, with Matthew's correlation coefficient of 80.34%. The predicted results on an independent test data achieved 87.71% as accuracy and 75.43% of Matthew's correlation coefficient, better than the prediction from the best ubiquitination site prediction tool available.Our study may guide experimental design and provide useful insights for studying the mechanisms and modulation of ubiquitination pathways. The code is available at: https://github.com/Chunhuixu/UBIPredic_QWRCHX.