Prediction of potential disease-associated microRNAs using structural perturbation method

Motivation: The identification of disease-related microRNAs (miRNAs) is an essential but challenging task in bioinformatics research. Similarity-based link prediction methods are often used to predict potential associations between miRNAs and diseases. In these methods, all unobserved associations are ranked by their similarity scores. Higher score indicates higher probability of existence. However, most previous studies mainly focus on designing advanced methods to improve the prediction accuracy while neglect to investigate the link predictability of the networks that present the miRNAs and diseases associations. In this work, we construct a bilayer network by integrating the miRNA-disease network, the miRNA similarity network and the disease similarity network. We use structural consistency as an indicator to estimate the link predictability of the related networks. On the basis of the indicator, a derivative algorithm, called structural perturbation method (SPM), is applied to predict potential associations between miRNAs and diseases. Results: The link predictability of bilayer network is higher than that of miRNA-disease network, indicating that the prediction of potential miRNAs-diseases associations on bilayer network can achieve higher accuracy than based merely on the miRNA-disease network. A comparison between the SPM and other algorithms reveals the reliable performance of SPM which performed well in a 5-fold cross-validation. We test fifteen networks. The AUC values of SPM are higher than some well-known methods, indicating that SPM could serve as a useful computational method for improving the identification accuracy of miRNA-disease associations. Moreover, in a case study on breast neoplasm, 80% of the top-20 predicted miRNAs have been manually confirmed by previous experimental studies.