Attentional multi-level representation encoding based on convolutional and variance autoencoders for lncRNA-disease association prediction.

Abstract

As the abnormalities of long non-coding RNAs (lncRNAs) are closely related to various human diseases, identifying disease-related lncRNAs is important for understanding the pathogenesis of complex diseases. Most of current data-driven methods for disease-related lncRNA candidate prediction are based on diseases and lncRNAs. Those methods, however, fail to consider the deeply embedded node attributes of lncRNA-disease pairs, which contain multiple relations and representations across lncRNAs, diseases and miRNAs. Moreover, the low-dimensional feature distribution at the pairwise level has not been taken into account. We propose a prediction model, VADLP, to extract, encode and adaptively integrate multi-level representations. Firstly, a triple-layer heterogeneous graph is constructed with weighted inter-layer and intra-layer edges to integrate the similarities and correlations among lncRNAs, diseases and miRNAs. We then define three representations including node attributes, pairwise topology and feature distribution. Node attributes are derived from the graph by an embedding strategy to represent the lncRNA-disease associations, which are inferred via their common lncRNAs, diseases and miRNAs. Pairwise topology is formulated by random walk algorithm and encoded by a convolutional autoencoder to represent the hidden topological structural relations between a pair of lncRNA and disease. The new feature distribution is modeled by a variance autoencoder to reveal the underlying lncRNA-disease relationship. Finally, an attentional representation-level integration module is constructed to adaptively fuse the three representations for lncRNA-disease association prediction. The proposed model is tested over a public dataset with a comprehensive list of evaluations. Our model outperforms six state-of-the-art lncRNA-disease prediction models with statistical significance. The ablation study showed the important contributions of three representations. In particular, the improved recall rates under different top $k$ values demonstrate that our model is powerful in discovering true disease-related lncRNAs in the top-ranked candidates. Case studies of three cancers further proved the capacity of our model to discover potential disease-related lncRNAs.