DPMGCDA: Deciphering circRNA–Drug Sensitivity Associations with Dual Perspective Learning and Path-Masked Graph Autoencoder

Accumulating evidence has indicated that the expression of circular RNAs (circRNAs) can affect the cellular sensitivity to drugs and significantly influence drug efficacy. However, traditional experimental approaches for validating these associations are resource-intensive and time-consuming. To address this challenge, we propose a computational framework termed DPMGCDA leveraging dual perspective learning and path-masked graph autoencoder to predict circRNA-drug sensitivity associations. Initially, we construct circRNA-circRNA fusion similarity networks and drug-drug fusion similarity networks using similarity network fusion, ensuring a comprehensive integration of information. Based on the above, we built the circRNA homogeneous graph, the drug homogeneous graph, and the circRNA-drug heterogeneous graph. Next, we form the initial node features in the circRNA-drug heterogeneous graph from the homogeneous graph-level perspective and the combined feature-level perspective and complete the prediction of potential associations using the path-masked graph autoencoder in both perspectives. The predictions under both perspectives are finally combined to obtain the final prediction score. Transductive setting experiments and inductive setting experiments all demonstrate that our method, DPMGCDA, outperforms state-of-the-art approaches. Additionally, we verify the necessity of employing dual perspective learning through ablation tests and analyze the effective encoding capability of the path-masked graph autoencoder for features through embedding visualization. Moreover, case studies on four drugs corroborate DPMGCDA's ability to identify potential circRNAs associated with new drugs.