LAUSR

ABSTRACT Accumulating studies have shown that microRNAs (miRNAs) could be used as targets of small-molecule (SM) drugs to treat diseases. In recent years, researchers have proposed many computational models to reveal miRNA-SM associations due to the huge cost of experimental methods. Considering the shortcomings of the previous models, such as the prediction accuracy of some models is low or some cannot be applied for new SMs (miRNAs), we developed a novel model named Symmetric Nonnegative Matrix Factorization for Small Molecule-MiRNA Association prediction (SNMFSMMA). Different from some models directly applying the integrated similarities, SNMFSMMA first performed matrix decomposition on the integrated similarity matrixes, and calculated the Kronecker product of the new integrated similarity matrixes to obtain the SM-miRNA pair similarity. Further, we applied regularized least square to obtain the mapping function of the SM-miRNA pairs to the associated probabilities by minimizing the objective function. On the basis of Dataset 1 and 2 extracted from SM2miR v1.0 database, we implemented global leave-one-out cross validation (LOOCV), miRNA-fixed local LOOCV, SM-fixed local LOOCV and 5-fold cross-validation to evaluate the prediction performance. Finally, the AUC values obtained by SNMFSMMA in these validation reached 0.9711 (0.8895), 0.9698 (0.8884), 0.8329 (0.7651) and 0.9644 ± 0.0035 (0.8814 ± 0.0033) based on Dataset 1 (Dataset 2), respectively. In the first case study, 5 of the top 10 associations predicted were confirmed. In the second, 7 and 8 of the top 10 predicted miRNAs related with 5-FU and 5-Aza-2ʹ-deoxycytidine were confirmed. These results demonstrated the reliable predictive power of SNMFSMMA.