Predicting CircRNA-Disease Associations Through Non-negative Matrix Factorization and Adversarially Regularized Variational Graph Autoencoder

Circular RNA (circRNA) is an RNA molecule that plays an important role in both pathology and physiology. Accurate identification of associations between circRNAs and diseases is crucial for further physiology research. However, verifying the circRNA-disease associations (CDA) through biological experimental methods is time-consuming. Here, we propose a novel method combines Non-negative Matrix Factorization (NMF) and Adversarially Regularized Variational Graph Autoencoder (ARVGA) to accurately predict CDA. Our model first fuses multi-source information in order to build circRNA similarity, disease similarity and circRNA-disease association matrices. Thereby our model constructs graphs for circRNA and disease respectively and optimize them using a K-means clustering algorithm. We obtain linear features using NMF and non-linear features using ARVGA. Finally, an Extremely Randomized Trees classifier is employed to predict CDA. On the gold standard dataset CircR2Disease, our model achieved a prediction accuracy of 94.8% and an AUC of 0.984 under 5-fold cross-validation. In case study, 19 of top 20 predicted circRNAs associated with Hepatocellular Carcinoma were confirmed in relevant literature. Furthermore, ablation experiment, classifier experiment and independent datasets test fully demonstrate the effectiveness and robustness of our model.