Accumulating studies have demonstrated close relationships between long non-coding RNAs (lncRNAs) and diseases. Identification of new lncRNA-disease associations (LDAs) enables us to better understand disease mechanisms and further provides promising insights into cancer targeted therapy and anti-cancer drug design. Here, we present an LDA prediction framework called GEnDDn based on deep learning. GEnDDn mainly comprises two steps: First, features of both lncRNAs and diseases are extracted by combining similarity computation, non-negative matrix factorization, and graph attention auto-encoder, respectively. And each lncRNA-disease pair (LDP) is depicted as a vector based on concatenation operation on the extracted features. Subsequently, unknown LDPs are classified by aggregating dual-net neural architecture and deep neural network. Using six different evaluation metrics, we found that GEnDDn surpassed four competing LDA identification methods (SDLDA, LDNFSGB, IPCARF, LDASR) on the lncRNADisease and MNDR databases under fivefold cross-validation experiments on lncRNAs, diseases, LDPs, and independent lncRNAs and independent diseases, respectively. Ablation experiments further validated the powerful LDA prediction performance of GEnDDn. Furthermore, we utilized GEnDDn to find underlying lncRNAs for lung cancer and breast cancer. The results elucidated that there may be dense linkages between IFNG-AS1 and lung cancer as well as between HIF1A-AS1 and breast cancer. The results require further biomedical experimental verification. GEnDDn is publicly available at https://github.com/plhhnu/GEnDDn.
Keywords: Deep neural network; Dual-net neural network; Graph attention auto-encoder; Non-negative matrix factorization; lncRNA–disease association.
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