Combining K Nearest Neighbor With Nonnegative Matrix Factorization for Predicting Circrna-Disease Associations

Accumulating evidences show that circular RNAs (circRNAs) play an important role in regulating gene expression, and involve in many complex human diseases. Identifying associations of circRNA with disease helps to understand the pathogenesis, treatment and diagnosis of complex diseases. Since inferring circRNA-disease associations by biological experiments is costly and time-consuming, there is an urgently need to develop a computational model to identify the association between them. In this paper, we proposed a novel method named KNN-NMF, which combines <inline-formula><tex-math notation="LaTeX">$K\ $</tex-math><alternatives><mml:math><mml:mrow><mml:mi>K</mml:mi><mml:mspace width="4pt"/></mml:mrow></mml:math><inline-graphic xlink:href="wang-ieq1-3180903.gif"/></alternatives></inline-formula>nearest neighbors with nonnegative matrix factorization to infer associations between circRNA and disease (KNN-NMF). Frist, we compute the Gaussian Interaction Profile (GIP) kernel similarity of circRNA and disease, the semantic similarity of disease, respectively. Then, the circRNA-disease new interaction profiles are established using weight <inline-formula><tex-math notation="LaTeX">$K$</tex-math><alternatives><mml:math><mml:mi>K</mml:mi></mml:math><inline-graphic xlink:href="wang-ieq2-3180903.gif"/></alternatives></inline-formula> nearest neighbors to reduce the false negative association impact on prediction performance. Finally, Nonnegative Matrix Factorization is implemented to predict associations of circRNA with disease. The experiment results indicate that the prediction performance of KNN-NMF outperforms the competing methods under five-fold cross-validation. Moreover, case studies of two common diseases further show that KNN-NMF can identify potential circRNA-disease associations effectively.