Predicting associations between CircRNA and diseases through structure-aware graph transformer and path-integral convolution

Abstract

A series of biological experiments has demonstrated that circular RNAs play a crucial regulatory role in cellular processes and may be potentially associated with diseases. Uncovering these connections helps in understanding potential disease mechanisms and advancing the development of treatment strategies. However, in biology, traditional experiments face limitations in terms of efficiency and cost, especially when enumerating possible associations. To address these limitations, several computational methods have been proposed, but existing methods only measure from a nodal perspective and cannot capture structural similarities between edges. In this study, we introduce an advanced computational method called SATPIC2CD for analyzing potential associations between circular RNAs and diseases. Specifically, we first employ an Structure-Aware Graph Transformer (SAT), which extracts five predefined metapath representations before calculating attention. This adaptive network integrates structural information into the original self-attention by aggregating information within and between paths. Subsequently, we use Path Integral Convolutional Networks (PACN) to integrate feature information for all path weights between two nodes. Afterward, we complement the network node features with feature loss and feature smoothing using Gated Recurrent Units (GRU) and node centrality. Finally, a Multi-Layer Perceptron (MLP) is employed to obtain the ultimate prediction scores for each circular RNA-disease pair. SATPIC2CD performs remarkably well, with an accuracy of up to 0.9715 measured by the Area Under the Curve (AUC) in a 5-fold cross-validation, surpassing other comparative models. Case studies further emphasize the high precision of our method in identifying circular RNA-disease associations, laying a solid foundation for guiding future biological research efforts.