AMPCDA: Prediction of circRNA–disease associations by utilizing attention mechanisms on metapaths

Abstract

Researchers have been creating an expanding corpus of experimental evidences in biomedical field which has revealed prevalent associations between circRNAs and human diseases. Such linkages unveiled afforded a new perspective for elucidating etiology and devise innovative therapeutic strategies. In recent years, many computational methods were introduced to remedy the limitations of inefficiency and exorbitant budgets brought by conventional lab-experimental approaches to enumerate possible circRNA–disease associations, but the majority of existing methods still face challenges in effectively integrating node embeddings with higher-order neighborhood representations, which might hinder the final predictive accuracy from attaining optimal measures. To overcome such constraints, we proposed AMPCDA, a computational technique harnessing predefined metapaths to predict circRNA–disease associations. Specifically, an association graph is initially built upon three source databases and two similarity derivation procedures, and DeepWalk is subsequently imposed on the graph to procure initial feature representations. Vectorial embeddings of metapath instances, concatenated by initial node features, are then fed through a customed encoder. By employing self-attention section, metapath-specific contributions to each node are accumulated before combining with node’s intrinsic features and channeling into a graph attention module, which furnished the input representations for the multilayer perceptron to predict the ultimate association probability scores. By integrating graph topology features and node embedding themselves, AMPCDA managed to effectively leverage information carried by multiple nodes along paths and exhibited an exceptional predictive performance, achieving AUC values of 0.9623, 0.9675, and 0.9711 under 5-fold cross validation, 10-fold cross validation, and leave-one-out cross validation, respectively. These results signify substantial accuracy improvements compared to other prediction models. Case study assessments confirm the high predictive accuracy of our proposed technique in identifying circRNA–disease connections, highlighting its value in guiding future biological research to reveal new disease mechanisms.