School of Computer Science and Technology, Heilongjiang University, Harbin 150080, China.
Department of Computer Science and Information Technology, La Trobe University, Melbourne 3083, Australia.
Brief Bioinform. 2022 May 13;23(3). doi: 10.1093/bib/bbac089.
Since abnormal expression of long noncoding RNAs (lncRNAs) is often closely related to various human diseases, identification of disease-associated lncRNAs is helpful for exploring the complex pathogenesis. Most of recent methods concentrate on exploiting multiple kinds of data related to lncRNAs and diseases for predicting candidate disease-related lncRNAs. These methods, however, failed to deeply integrate the topology information from the meta-paths that are composed of lncRNA, disease and microRNA (miRNA) nodes. We proposed a new method based on fully connected autoencoders and convolutional neural networks, called ACLDA, for inferring potential disease-related lncRNA candidates. A heterogeneous graph that consists of lncRNA, disease and miRNA nodes were firstly constructed to integrate similarities, associations and interactions among them. Fully connected autoencoder-based module was established to extract the low-dimensional features of lncRNA, disease and miRNA nodes in the heterogeneous graph. We designed the attention mechanisms at the node feature level and at the meta-path level to learn more informative features and meta-paths. A module based on convolutional neural networks was constructed to encode the local topologies of lncRNA and disease nodes from multiple meta-path perspectives. The comprehensive experimental results demonstrated ACLDA achieves superior performance than several state-of-the-art prediction methods. Case studies on breast, lung and colon cancers demonstrated that ACLDA is able to discover the potential disease-related lncRNAs.
由于长链非编码 RNA(lncRNA)的异常表达通常与各种人类疾病密切相关,因此鉴定与疾病相关的 lncRNA 有助于探索复杂的发病机制。大多数最近的方法都集中于利用与 lncRNA 和疾病相关的多种数据来预测候选疾病相关的 lncRNA。然而,这些方法未能深入整合由 lncRNA、疾病和 microRNA(miRNA)节点组成的元路径的拓扑信息。我们提出了一种基于全连接自动编码器和卷积神经网络的新方法,称为 ACLDA,用于推断潜在的疾病相关 lncRNA 候选物。首先构建了一个包含 lncRNA、疾病和 miRNA 节点的异构图,以整合它们之间的相似性、关联和相互作用。基于全连接自动编码器的模块用于提取异构图中 lncRNA、疾病和 miRNA 节点的低维特征。我们在节点特征级别和元路径级别设计了注意力机制,以学习更具信息量的特征和元路径。基于卷积神经网络的模块用于从多个元路径角度对 lncRNA 和疾病节点的局部拓扑结构进行编码。综合实验结果表明,ACLDA 优于几种最新的预测方法。乳腺癌、肺癌和结肠癌的案例研究表明,ACLDA 能够发现潜在的疾病相关 lncRNA。