SPRINT-Gly: predicting N- and O-linked glycosylation sites of human and mouse proteins by using sequence and predicted structural properties

Motivation: Protein glycosylation is one of the most abundant post-translational modifications that plays an important role in immune responses, intercellular signaling, inflammation and host-pathogen interactions. However, due to the poor ionization efficiency and microheterogeneity of glycopeptides identifying glycosylation sites is a challenging task, and there is a demand for computational methods. Here, we constructed the largest dataset of human and mouse glycosylation sites to train deep learning neural networks and support vector machine classifiers to predict N-/O-linked glycosylation sites, respectively. Results: The method, called SPRINT-Gly, achieved consistent results between ten-fold cross validation and independent test for predicting human and mouse glycosylation sites. For N-glycosylation, a mouse-trained model performs equally well in human glycoproteins and vice versa, however, due to significant differences in O-linked sites separate models were generated. Overall, SPRINT-Gly is 18% and 50% higher in Matthews correlation coefficient than the next best method compared in N-linked and O-linked sites, respectively. This improved performance is due to the inclusion of novel structure and sequence-based features.