A Novel Deep Learning Method for Predicting RNA-Protein Binding Sites

The cell cycle and biological processes rely on RNA and RNA-binding protein (RBP) interactions. It is crucial to identify the binding sites on RNA. Various deep-learning methods have been used for RNA-binding site prediction. However, they cannot extract the hierarchical features of the RNA secondary structure. Therefore, this paper proposes HPNet, which can automatically identify RNA-binding sites and -binding preferences. HPNet performs feature learning from the two perspectives of the RNA sequence and the RNA secondary structure. A convolutional neural network (CNN), a deep-learning method, is used to learn RNA sequence features in HPNet. To capture the hierarchical information for RNA, we introduced DiffPool into HPNet, a differentiable pooling graph neural network (GNN). A CNN and DiffPool were combined to improve the binding site prediction accuracy by leveraging both RNA sequence features and hierarchical features of the RNA secondary structure. Binding preferences can be extracted based on model outputs and parameters. Overall, the experimental results showed that HPNet achieved a mean area under the curve (AUC) of 94.5% for the benchmark dataset, which was more accurate than the state-of-the-art methods. Moreover, these results demonstrate that the hierarchical features of RNA secondary structure play an essential role in selecting RNA-binding sites.