RMDGCN: Prediction of RNA methylation and disease associations based on graph convolutional network with attention mechanism

RNA modification is a post transcriptional modification that occurs in all organisms and plays a crucial role in the stages of RNA life, closely related to many life processes. As one of the newly discovered modifications, N1-methyladenosine (m1A) plays an important role in gene expression regulation, closely related to the occurrence and development of diseases. However, due to the low abundance of m1A, verifying the associations between m1As and diseases through wet experiments requires a great quantity of manpower and resources. In this study, we proposed a computational method for predicting the associations of RNA methylation and disease based on graph convolutional network (RMDGCN) with attention mechanism. We build an adjacency matrix through the collected m1As and diseases associations, and use positive-unlabeled learning to increase the number of positive samples. By extracting the features of m1As and diseases, a heterogeneous network is constructed, and a GCN with attention mechanism is adopted to predict the associations between m1As and diseases. The experimental results indicate that under a 5-fold cross validation, RMDGCN is superior to other methods (AUC = 0.9892 and AUPR = 0.8682). In addition, case studies indicate that RMDGCN can predict the relationships between unknown m1As and diseases. In summary, RMDGCN is an effective method for predicting the associations between m1As and diseases.Author summary: As a new epitranscriptomic modification, m1A plays an important role in the gene expression regulation, closely related to the occurrence and development of diseases.However, due to the low abundance of m1A, verifying the associations between m1As and diseases through wet experiments requires a great quantity of manpower and resources.It is especially important to develop computational methods for predicting the associations between m1A modifications and diseases.We developed a deep learning model to predict the associations of m1As and diseases, namely RMDGCN.RMDGCN increases the number of known relationships between m1As and diseases through PU learning, and combines m1A similarity network and disease similarity network to construct heterogeneous networks. It adopts GCN with layered attention mechanism to predict the associations between methylations and diseases.The results of the 5-fold cross validation show that the performance of RMDGCN is superior to other comparison algorithms.Through case study analysis of breast cancer, RMDGCN can effectively predict the relationships between unknown m1As and diseases.