Inferring circRNA–Disease Associations via Sparse Topological Representation Learning and Dual-View Decoding

Circular RNAs (circRNAs) are key regulators in the onset and progression of complex diseases, offering promise as diagnostic and prognostic biomarkers. However, most putative circRNA-disease associations remain experimentally unverified, largely due to the cost and time demands of wet-lab approaches. To bridge this gap, we present STRCDA (Sparse Topological Representation learning for CircRNA-Disease Associations). The pipeline first constructs fused similarity profiles for circRNAs and diseases by integrating diverse biological attributes. These initial matrices are then refined via random walk with restart to capture local features. Subsequently, a sparse-constrained dual-branch graph autoencoder extracts holistic topological embeddings from the refined local features and the known interaction network. Finally, an XGBoost classifier scores potential circRNA-disease pairs. On the CircR2Disease dataset, STRCDA achieves an AUC of 0.9771 and an AUPR of 0.9826 under five-fold cross-validation. Notably, 18 of the top 20 predicted associations were confirmed by independent experimental evidence, highlighting STRCDA's efficacy as a robust tool for uncovering circRNA function in disease.