Predicting lncRNA-disease associations based on heterogeneous graph convolutional generative adversarial network

Author:

Lu ZhonghaoORCID,Zhong Hua,Tang Lin,Luo Jing,Zhou Wei,Liu LinORCID

Abstract

There is a growing body of evidence indicating the crucial roles that long non-coding RNAs (lncRNAs) play in the development and progression of various diseases, including cancers, cardiovascular diseases, and neurological disorders. However, accurately predicting potential lncRNA-disease associations remains a challenge, as existing methods have limitations in extracting heterogeneous association information and handling sparse and unbalanced data. To address these issues, we propose a novel computational method, called HGC-GAN, which combines heterogeneous graph convolutional neural networks (GCN) and generative adversarial networks (GAN) to predict potential lncRNA-disease associations. Specifically, we construct a lncRNA-miRNA-disease heterogeneous network by integrating multiple association data and sequence information. The GCN-based generator is then employed to aggregate neighbor information of nodes and obtain node embeddings, which are used to predict lncRNA-disease associations. Meanwhile, the GAN-based discriminator is trained to distinguish between real and fake lncRNA-disease associations generated by the generator, enabling the generator to improve its ability to generate accurate lncRNA-disease associations gradually. Our experimental results demonstrate that HGC-GAN performs better in predicting potential lncRNA-disease associations, with AUC and AUPR values of 0.9591 and 0.9606, respectively, under 10-fold cross-validation. Moreover, our case study further confirms the effectiveness of HGC-GAN in predicting potential lncRNA-disease associations, even for novel lncRNAs without any known lncRNA-disease associations. Overall, our proposed method HGC-GAN provides a promising approach to predict potential lncRNA-disease associations and may have important implications for disease diagnosis, treatment, and drug development.

Funder

National Natural Science Foundation of China

Applied Basic Research Project in Yunnan Province

Yunnan Provincial Science and Technology Department-Yunnan University Double First-Class Joint Fund Key Projects

National Key R&D Program of China

Publisher

Public Library of Science (PLoS)

Subject

Computational Theory and Mathematics,Cellular and Molecular Neuroscience,Genetics,Molecular Biology,Ecology,Modeling and Simulation,Ecology, Evolution, Behavior and Systematics

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