Identifying Potential miRNA-Disease Associations Based on an Improved Manifold Learning Framework

Adequate evidence has shown that miRNA-disease interactions are strongly involved in the pathological processes of complex human diseases. However, it is commonly time-consuming and labor-intensive to utilize laboratory biological experiments to reveal unknown miRNA-disease pairs. Since the previously proposed calculation model has more or fewer deficiencies, we developed the semi-supervised method called Hessian Regularized Non-negative Matrix Factorization Method for miRNA-disease Association prediction (HRNMFMDA). This model introduced Hessian regularization into the NMF framework to preserve the local manifold information and increased an $l_{2,1}$ -norm penalty term to ensure the feature selection of the coding matrix and an approximate orthogonal constraint to obtain discriminative information. In the model performance evaluation, HRNMFMDA outperformed eight existing models, achieving AUC values of 0.9074, 0.8618, and 0.9044+/-0.0080 in the global leave-one-out cross-validation (LOOCV), local LOOCV and 5-fold cross-validation, respectively. In addition, we applied HRNMFMDA to several high-incidence human carcinomas via three kinds of case studies. Almost all predicted miRNAs were confirmed by external databases derived from experimental literature. Therefore, the conclusion can be drawn that HRNMFMDA is reliable for revealing uncovered miRNA-disease pairs.