THGNCDA: circRNA–disease association prediction based on triple heterogeneous graph network

Abstract

Abstract Circular RNAs (circRNAs) are a class of noncoding RNA molecules featuring a closed circular structure. They have been proved to play a significant role in the reduction of many diseases. Besides, many researches in clinical diagnosis and treatment of disease have revealed that circRNA can be considered as a potential biomarker. Therefore, understanding the association of circRNA and diseases can help to forecast some disorders of life activities. However, traditional biological experimental methods are time-consuming. The most common method for circRNA–disease association prediction on the basis of machine learning can avoid this, which relies on diverse data. Nevertheless, topological information of circRNA and disease usually is not involved in these methods. Moreover, circRNAs can be associated with diseases through miRNAs. With these considerations, we proposed a novel method, named THGNCDA, to predict the association between circRNAs and diseases. Specifically, for a certain pair of circRNA and disease, we employ a graph neural network with attention to learn the importance of its each neighbor. In addition, we use a multilayer convolutional neural network to explore the relationship of a circRNA–disease pair based on their attributes. When calculating embeddings, we introduce the information of miRNAs. The results of experiments show that THGNCDA outperformed the SOTA methods. In addition, it can be observed that our method gives a better recall rate. To confirm the significance of attention, we conducted extensive ablation studies. Case studies on Urinary Bladder and Prostatic Neoplasms further show THGNCDA’s ability in discovering known relationships between circRNA candidates and diseases.