Abstract
Accumulating evidence shows that circular RNAs (circRNAs) have significant roles in human health and in the occurrence and development of diseases. Biological researchers have identified disease-related circRNAs that could be considered as potential biomarkers for clinical diagnosis, prognosis, and treatment. However, identification of circRNA-disease associations using traditional biological experiments is still expensive and time-consuming. In this study, we propose a novel method named MSFCNN for the task of circRNA-disease association prediction, involving two-layer convolutional neural networks on a feature matrix that fuses multiple similarity kernels and interaction features among circRNAs, miRNAs, and diseases. First, four circRNA similarity kernels and seven disease similarity kernels are constructed based on the biological or topological properties of circRNAs and diseases. Subsequently, the similarity kernel fusion method is used to integrate the similarity kernels into one circRNA similarity kernel and one disease similarity kernel, respectively. Then, a feature matrix for each circRNA-disease pair is constructed by integrating the fused circRNA similarity kernel and fused disease similarity kernel with interactions and features among circRNAs, miRNAs, and diseases. The features of circRNA-miRNA and disease-miRNA interactions are selected using principal component analysis. Finally, taking the constructed feature matrix as an input, we used two-layer convolutional neural networks to predict circRNA-disease association labels and mine potential novel associations. Five-fold cross validation shows that our proposed model outperforms conventional machine learning methods, including support vector machine, random forest, and multilayer perception approaches. Furthermore, case studies of predicted circRNAs for specific diseases and the top predicted circRNA-disease associations are analyzed. The results show that the MSFCNN model could be an effective tool for mining potential circRNA-disease associations.