Accumulating experimental studies have indicated the influence of lncRNAs on various critical biological processes as well as disease development and progression. Calculating lncRNA functional similarity is of high value in inferring lncRNA functions and identifying potential lncRNA-disease associations. However, little effort has been attempt to measure the functional similarity among lncRNAs on a large scale. In this study, we developed a Fuzzy Measure-based LNCRNA functional SIMilarity calculation model (FMLNCSIM) based on the assumption that functionally similar lncRNAs tend to be associated with similar diseases. The performance improvement of FMLNCSIM mainly comes from the combination of information content and the concept of fuzzy measure, which was applied to the directed acyclic graphs of disease MeSH descriptors. To evaluate the effectiveness of FMLNCSIM, we further combined it with the previously proposed model of Laplacian Regularized Least Squares for lncRNA-Disease Association (LRLSLDA). As a result, the integrated model, LRLSLDA-FMLNCSIM, achieve good performance in the frameworks of global LOOCV (AUCs of 0.8266 and 0.9338 based on LncRNADisease and MNDR database) and 5-fold cross validation (average AUCs of 0.7979 and 0.9237 based on LncRNADisease and MNDR database), which significantly improve the performance of previous classical models. It is anticipated that FMLNCSIM could be used for searching functionally similar lncRNAs and inferring lncRNA functions in the future researches.
Keywords: directed acyclic graph; disease; functional similarity; fuzzy measure; lncRNAs.