NARVGA: A Hybrid Framework Integrating Matrix Factorisation and Adversarial Graph Learning for circRNA-Disease Association Prediction.

Circular RNAs (circRNAs) participate in gene regulation and disease progression, but experimental mapping of circRNA-disease associations (CDAs) remains costly and incomplete. We developed NARVGA, a hybrid prediction framework that combines non-negative matrix factorisation (NMF) with an adversarially regularised variational graph autoencoder (ARVGA). Functional, semantic and Gaussian interaction-profile kernel similarities are integrated; K-means-derived co-membership graphs reduce diffuse similarity connections; ARVGA learns nonlinear topological embeddings; and NMF captures complementary low-rank association patterns. An Extra Trees classifier then scores candidate circRNA-disease pairs. In the original transductive stratified five-fold benchmark on CircR2Disease, NARVGA achieved an area under the receiver operating characteristic curve (AUC) of 0.9868, an area under the precision-recall curve (AUPR) of 0.9887, 94.32% accuracy and a 94.44% F1-score. Ablation analysis identified cluster sparsification as the largest individual contributor, with additional gains from adversarial regularisation and low-rank augmentation. Without task-specific retuning, the model obtained AUCs of 0.9503 on LncRNADisease and 0.9700 on HMDDv4. Performance was stable across GCN depths and cluster settings, and 19 of the 20 highest-ranked hepatocellular carcinoma candidates had supporting published evidence. NARVGA provides a within-network prioritisation tool for RNA-disease association studies, although prospective validation, hard-negative assessment and independent-cohort testing remain necessary.