Specific topology and topological connection sensitivity enhanced graph learning for lncRNA-disease association prediction

Abstract

Predicting disease-related candidate long noncoding RNAs (lncRNAs) is beneficial for exploring disease pathogenesis due to the close relations between lncRNAs and the occurrence and development of human diseases. It is a long-term and challenging task to adequately extract specific and local topologies in individual lncRNA network and individual disease network, and integrate the information of the connection relationships. We propose a new graph learning-based prediction method to encode specific and local topologies from each individual network, neighbor topologies with different connection relationships, and pairwise attributes. We first construct a lncRNA network composed of all the lncRNA nodes and their similarities, and a single disease network that contains all the disease nodes and disease similarities. Then, a network-aware graph convolutional autoencoder is constructed to encode the specific and local topologies of each network. Secondly, a heterogeneous network is established to embed all lncRNA, disease, and miRNA nodes and their various connections. Afterwards, a connection-sensitive graph neural network is designed to deeply integrate the neighbor node attributes and connection characteristics in the heterogeneous network and learn neighbor topological representations. We also construct both connection-level and topology representation-level attention mechanisms to extract informative connections and topological representations. Finally, we build a multi-layer convolutional neural networks with weighted residuals to adaptively complement the detailed features to pairwise attribute encoding. Comprehensive experiments and comparison results demonstrated that NCPred outperforms seven state-of-the-art prediction methods. The ablation studies demonstrated the importance of local topology learning, neighbor topology learning, and pairwise attribute encoding. Case studies on prostate, lung, and breast cancers further revealed NCPred's capacity to screen potential candidate disease-related lncRNAs.

Keywords: Connection-sensitive graph learning; Learning specific topology of individual network; LncRNA–disease association prediction; Pairwise attribute encoding with detail complement; Representation-level attention mechanism.