RLNSF-MDA: reliability-guided graph-regularized matrix factorization for immune-related miRNA-disease association...

MicroRNAs (miRNAs) regulate gene expression and are closely linked to the onset and progression of immune‑related diseases. Experimental discovery of disease‑associated miRNAs remains costly and time‑consuming, motivating computational prioritization. However, existing matrix‑completion and deep graph‑learning methods either underuse local biological neighborhood evidence or require complex multi‑view neural architectures.

In this study, we present RLNSF‑MDA, a reliability‑guided graph‑regularized logistic matrix factorization framework for predicting potential miRNA-disease associations, with an emphasis on immune disease analysis. The method integrates disease semantic similarity; miRNA functional, semantic, and sequence similarities; and training‑only Gaussian interaction profile similarities through data‑driven reliability weights. It then combines multi‑scale neighborhood evidence, diffusion scores, low‑rank reconstruction features, and contrastive graph‑regularized latent factors.

On the HMDD v3.2 benchmark containing 788 miRNAs and 374 diseases, RLNSF‑MDA achieved an average accuracy of 0.8525, an AUC of 0.9194, and an AUPR of 0.9055 in five‑fold cross‑validation, and an average accuracy of 0.8569, an AUC of 0.9266, and an AUPR of 0.9197 in ten‑fold cross‑validation. Ablation experiments showed that the full model outperformed reduced feature combinations and training strategies, supporting the contribution of reliability‑guided fusion, side‑score construction, graph regularization, and contrastive ranking. Evidence from immune‑related case studies in dbDEMC V2.0 and miR2Disease further covered lupus nephritis, lymphoma, and leukemia, with 45, 47, and 47 confirmed miRNAs, respectively.

These results suggest that RLNSF‑MDA provides an effective and interpretable framework for prioritizing candidate miRNAs associated with immune‑related diseases.