PDMDA: predicting deep-level miRNA-disease associations with graph neural networks and sequence features

Abstract

Motivation: Many studies have shown that microRNAs (miRNAs) play a key role in human diseases. Meanwhile, traditional experimental methods for miRNA-disease association identification are extremely costly, time-consuming and challenging. Therefore, many computational methods have been developed to predict potential associations between miRNAs and diseases. However, those methods mainly predict the existence of miRNA-disease associations, and they cannot predict the deep-level miRNA-disease association types.

Results: In this study, we propose a new end-to-end deep learning method (called PDMDA) to predict deep-level miRNA-disease associations with graph neural networks (GNNs) and miRNA sequence features. Based on the sequence and structural features of miRNAs, PDMDA extracts the miRNA feature representations by a fully connected network (FCN). The disease feature representations are extracted from the disease-gene network and gene-gene interaction network by GNN model. Finally, a multilayer with three fully connected layers and a softmax layer is designed to predict the final miRNA-disease association scores based on the concatenated feature representations of miRNAs and diseases. Note that PDMDA does not take the miRNA-disease association matrix as input to compute the Gaussian interaction profile similarity. We conduct three experiments based on six association type samples (including circulations, epigenetics, target, genetics, known association of which their types are unknown and unknown association samples). We conduct fivefold cross-validation validation to assess the prediction performance of PDMDA. The area under the receiver operating characteristic curve scores is used as metric. The experiment results show that PDMDA can accurately predict the deep-level miRNA-disease associations.

Availability and implementation: Data and source codes are available at https://github.com/27167199/PDMDA.