Graph-Based Prediction of miRNA-Drug Associations with Multisource Information and Metapath Enhancement Matrices

Recent studies have demonstrated that miRNA expression dysregulation is closely related to the occurrence of various diseases; thus, miRNA-based drug development strategies have received increasing research interest. Most existing computational methods focus on the attribute information of individual nodes and are limited to the direct associations between nodes, thereby ignoring the complex associations inherent in the network. This limitation may lead to the loss of key potential information, which impacts the prediction accuracy. To address these issues, we propose a multisource information fusion and metapath enhancement matrix based graph autoencoder (MSMP-GAE) to predict the potential associations between miRNAs and drugs. The proposed MSMP-GAE model comprises a metapath instance extraction module, a metapath feature-enhanced encoder module, a weighted feature fusion module, and a graph autoencoder. First, we construct an miRNA-drug heterogeneous network using experimentally validated miRNA-drug interactions and integrate various miRNA and drug features into an initial feature matrix to comprehensively represent their intrinsic property information. Then, we extract metapath instances from the interaction network, generate multiple metapath enhancement matrices, and fuse them with the initial feature matrix to generate high-quality node feature embeddings. Finally, we employ the graph autoencoder for fivefold cross-validation on a public dataset and test it on an independent test set. Experimental results demonstrate that the proposed MSMP-GAE model obtained an area under the curve (AUC) and AUPR values of 98.61% and 98.23%, respectively, which is considerably better than the several state-of-the-art methods. This highlights the importance of the higher-order complex associations between nodes in the miRNA-drug association (MDA) prediction task and provides a new method and approach to advance MDA prediction.