Recurrent neural network-based prediction of O-GlcNAcylation sites in mammalian proteins

Abstract

O-GlcNAcylation has the potential to be an important target for therapeutics, but a motif or an algorithm to reliably predict O-GlcNAcylation sites is not available. Current predictive models are insufficient as they fail to generalize, and many are no longer available. This article constructs recurrent neural network models to predict O-GlcNAcylation sites based on protein sequences. Different datasets are evaluated separately and assessed in terms of strengths and issues. Within a given dataset, results are robust to changes in cross-validation and test data as determined by nested validation. The best model achieves an F${}_1$ score of 36% (more than 3.5-fold greater than the previous best model) and a Matthews Correlation Coefficient of 35% (more than 4.5-fold greater than the previous best model), and, for the F${}_1$ score, 7.6-fold higher than when not using any model. Shapley values are used to interpret the model’s predictions and provide biological insight into O-GlcNAcylation.