SVMMDR: Prediction of miRNAs-drug resistance using support vector machines based on heterogeneous network

Abstract

In recent years, the miRNA is considered as a potential high-value therapeutic target because of its complex and delicate mechanism of gene regulation. The abnormal expression of miRNA can cause drug resistance, affecting the therapeutic effect of the disease. Revealing the associations between miRNAs-drug resistance can help in the design of effective drugs or possible drug combinations. However, current conventional experiments for identification of miRNAs-drug resistance are time-consuming and high-cost. Therefore, it's of pretty realistic value to develop an accurate and efficient computational method to predicting miRNAs-drug resistance. In this paper, a method based on the Support Vector Machines (SVM) to predict the association between MiRNA and Drug Resistance (SVMMDR) is proposed. The SVMMDR integrates miRNAs-drug resistance association, miRNAs sequence similarity, drug chemical structure similarity and other similarities, extracts path-based Hetesim features, and obtains inclined diffusion feature through restart random walk. By combining the multiple feature, the prediction score between miRNAs and drug resistance is obtained based on the SVM. The innovation of the SVMMDR is that the inclined diffusion feature is obtained by inclined restart random walk, the node information and path information in heterogeneous network are integrated, and the SVM is used to predict potential miRNAs-drug resistance associations. The average AUC of SVMMDR obtained is 0.978 in 10-fold cross-validation.

Keywords: drug resistance; hetesim score; miRNA; random walk with restart; support vector machines.