MNMDCDA: prediction of circRNA–disease associations by learning mixed neighborhood information from multiple distances

Abstract Emerging evidence suggests that circular RNA (circRNA) is an important regulator of a variety of pathological processes and serves as a promising biomarker for many complex human diseases. Nevertheless, there are relatively few known circRNA–disease associations, and uncovering new circRNA–disease associations by wet-lab methods is time consuming and costly. Considering the limitations of existing computational methods, we propose a novel approach named MNMDCDA, which combines high-order graph convolutional networks (high-order GCNs) and deep neural networks to infer associations between circRNAs and diseases. Firstly, we computed different biological attribute information of circRNA and disease separately and used them to construct multiple multi-source similarity networks. Then, we used the high-order GCN algorithm to learn feature embedding representations with high-order mixed neighborhood information of circRNA and disease from the constructed multi-source similarity networks, respectively. Finally, the deep neural network classifier was implemented to predict associations of circRNAs with diseases. The MNMDCDA model obtained AUC scores of 95.16%, 94.53%, 89.80% and 91.83% on four benchmark datasets, i.e., CircR2Disease, CircAtlas v2.0, Circ2Disease and CircRNADisease, respectively, using the 5-fold cross-validation approach. Furthermore, 25 of the top 30 circRNA–disease pairs with the best scores of MNMDCDA in the case study were validated by recent literature. Numerous experimental results indicate that MNMDCDA can be used as an effective computational tool to predict circRNA–disease associations and can provide the most promising candidates for biological experiments.