Abstract
Identification of disease-associated long non-coding RNAs (lncRNAs) is crucial for unveiling the underlying genetic mechanisms of complex diseases. Multiple types of similarity networks of lncRNAs (or diseases) can complementary and comprehensively characterize their similarities. Hence, in this study, we presented a computational model iLncDA-RSN based on reliable similarity networks for identifying potential lncRNA-disease associations (LDAs). Specifically, for constructing reliable similarity networks of lncRNAs and diseases, miRNA heuristic information with lncRNAs and diseases is firstly introduced to construct their respective Jaccard similarity networks; then Gaussian interaction profile (GIP) kernel similarity networks and Jaccard similarity networks of lncRNAs and diseases are provided based on the lncRNA-disease association network; a random walk with restart strategy is finally applied on Jaccard similarity networks, GIP kernel similarity networks, as well as lncRNA functional similarity network and disease semantic similarity network to construct reliable similarity networks. Depending on the lncRNA-disease association network and the reliable similarity networks, feature vectors of lncRNA-disease pairs are integrated from lncRNA and disease perspectives respectively, and then dimensionality reduced by the elastic net. Two random forests are at last used together on different lncRNA-disease association feature sets to identify potential LDAs. The iLncDA-RSN is evaluated by five-fold cross-validation to analyse its prediction performance, results of which show that the iLncDA-RSN outperforms the compared models. Furthermore, case studies of different complex diseases demonstrate the effectiveness of the iLncDA-RSN in identifying potential LDAs.