CircR2Disease v2.0: An Updated Web Server for Experimentally Validated circRNA-disease Associations and Its Application.

With accumulating dysregulated circular RNAs (circRNAs) in pathological processes, the regulatory functions of circRNAs, especially circRNAs as microRNA (miRNA) sponges and their interactions with RNA-binding proteins (RBPs), have been widely validated. However, the collected information on experimentally validated circRNA-disease associations is only preliminary. Therefore, an updated CircR2Disease database providing a comprehensive resource and web tool to clarify the relationships between circRNAs and diseases in diverse species is necessary. Here, we present an updated CircR2Disease v2.0 with the increased number of circRNA-disease associations and novel characteristics. CircR2Disease v2.0 provides more than 5-fold experimentally validated circRNA-disease associations compared to its previous version. This version includes 4201 entries between 3077 circRNAs and 312 disease subtypes. Secondly, the information of circRNA-miRNA, circRNA-miRNA-target, and circRNA-RBP interactions has been manually collected for various diseases. Thirdly, the gene symbols of circRNAs and disease name IDs can be linked with various nomenclature databases. Detailed descriptions such as samples and journals have also been integrated into the updated version. Thus, CircR2Disease v2.0 can serve as a platform for users to systematically investigate the roles of dysregulated circRNAs in various diseases and further explore the posttranscriptional regulatory function in diseases. Finally, we propose a computational method named circDis based on the graph convolutional network (GCN) and gradient boosting decision tree (GBDT) to illustrate the applications of the CircR2Disease v2.0 database. CircR2Disease v2.0 is available at http://bioinfo.snnu.edu.cn/CircR2Disease_v2.0 and https://github.com/bioinforlab/CircR2Disease-v2.0.