BPLLDA: Predicting lncRNA-Disease Associations Based on Simple Paths With Limited Lengths in a Heterogeneous Network

In recent years, it has been increasingly clear that long noncoding RNAs (lncRNAs) play critical roles in many biological processes associated with human diseases. Inferring potential lncRNA-disease associations is essential to reveal the secrets behind diseases, develop novel drugs, and optimize personalized treatments. However, biological experiments to validate lncRNA-disease associations are very time-consuming and costly. Thus, it is critical to develop effective computational models. In this study, we have proposed a method called BPLLDA to predict lncRNA-disease associations based on paths of fixed lengths in a heterogeneous lncRNA-disease association network. Specifically, BPLLDA first constructs a heterogeneous lncRNA-disease network by integrating the lncRNA-disease association network, the lncRNA functional similarity network, and the disease semantic similarity network. It then infers the probability of an lncRNA-disease association based on paths connecting them and their lengths in the network. Compared to existing methods, BPLLDA has a few advantages, including not demanding negative samples and the ability to predict associations related to novel lncRNAs or novel diseases. BPLLDA was applied to a canonical lncRNA-disease association database called LncRNADisease, together with two popular methods LRLSLDA and GrwLDA. The leave-one-out cross-validation areas under the receiver operating characteristic curve of BPLLDA are 0.87117, 0.82403, and 0.78528, respectively, for predicting overall associations, associations related to novel lncRNAs, and associations related to novel diseases, higher than those of the two compared methods. In addition, cervical cancer, glioma, and non-small-cell lung cancer were selected as case studies, for which the predicted top five lncRNA-disease associations were veri fied by recently published literature. In summary, BPLLDA exhibits good performances in predicting novel lncRNA-disease associations and associations related to novel lncRNAs and diseases. It may contribute to the understanding of lncRNA-associated diseases like certain cancers.