School of Information, Yunnan Normal University, Yunnan, People's Republic of China.
Key Laboratory of Educational Information for Nationalities Ministry of Education, Yunnan Normal University, Yunnan, People's Republic of China.
PLoS Comput Biol. 2023 Nov 29;19(11):e1011634. doi: 10.1371/journal.pcbi.1011634. eCollection 2023 Nov.
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.
越来越多的证据表明,长非编码 RNA(lncRNA)在各种疾病(包括癌症、心血管疾病和神经紊乱)的发展和进展中起着至关重要的作用。然而,准确预测潜在的 lncRNA-疾病关联仍然是一个挑战,因为现有的方法在提取异质关联信息和处理稀疏且不平衡的数据方面存在局限性。为了解决这些问题,我们提出了一种新的计算方法,称为 HGC-GAN,它结合了异构图卷积神经网络(GCN)和生成对抗网络(GAN)来预测潜在的 lncRNA-疾病关联。具体来说,我们通过整合多种关联数据和序列信息构建了 lncRNA-miRNA-疾病异构网络。然后,基于 GCN 的生成器被用来聚合节点的邻居信息并获得节点嵌入,这些节点嵌入用于预测 lncRNA-疾病关联。同时,基于 GAN 的鉴别器被训练来区分生成器生成的真实和虚假 lncRNA-疾病关联,从而使生成器能够逐渐提高生成准确 lncRNA-疾病关联的能力。我们的实验结果表明,HGC-GAN 在预测潜在的 lncRNA-疾病关联方面表现更好,在 10 倍交叉验证下 AUC 和 AUPR 值分别为 0.9591 和 0.9606。此外,我们的案例研究进一步证实了 HGC-GAN 在预测潜在的 lncRNA-疾病关联方面的有效性,即使对于没有任何已知 lncRNA-疾病关联的新型 lncRNA 也是如此。总体而言,我们提出的方法 HGC-GAN 为预测潜在的 lncRNA-疾病关联提供了一种有前途的方法,可能对疾病诊断、治疗和药物开发具有重要意义。