College of Life Science and Chemistry, Hunan University of Technology, Zhuzhou, 412007, China.
School of Computer Science, Hunan Institute of Technology, Hengyang, 421002, China.
Interdiscip Sci. 2024 Jun;16(2):418-438. doi: 10.1007/s12539-024-00619-w. Epub 2024 May 11.
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.
越来越多的研究表明,长非编码 RNA(lncRNA)与疾病之间存在密切关系。识别新的 lncRNA-疾病关联(LDA)使我们能够更好地理解疾病机制,并为癌症靶向治疗和抗癌药物设计提供有前途的见解。在这里,我们提出了一种基于深度学习的 LDA 预测框架,称为 GEnDDn。GEnDDn 主要包括两个步骤:首先,通过结合相似性计算、非负矩阵分解和图注意自动编码器,分别提取 lncRNA 和疾病的特征。并且,将每个 lncRNA-疾病对(LDP)描述为基于提取特征的串联操作的向量。随后,通过聚合双网络神经架构和深度神经网络对未知 LDP 进行分类。使用六种不同的评估指标,我们发现 GEnDDn 在 lncRNA、疾病、LDP 和独立 lncRNA 和独立疾病的五重交叉验证实验中,在 lncRNADisease 和 MNDR 数据库上均优于四个竞争 LDA 识别方法(SDLDA、LDNFSGB、IPCARF、LDASR)。消融实验进一步验证了 GEnDDn 强大的 LDA 预测性能。此外,我们利用 GEnDDn 发现了肺癌和乳腺癌的潜在 lncRNA。结果表明,IFNG-AS1 与肺癌之间以及 HIF1A-AS1 与乳腺癌之间可能存在密集的联系。这些结果需要进一步的生物医学实验验证。GEnDDn 可在 https://github.com/plhhnu/GEnDDn 上获得。