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基于多任务预测的图对比学习推断 lncRNAs、miRNAs 和疾病之间的关系。

Multi-task prediction-based graph contrastive learning for inferring the relationship among lncRNAs, miRNAs and diseases.

机构信息

Key laboratory of Symbol Computation and Knowledge Engineering of Ministry of Education, College of Computer Science and Technology, Jilin University, 130012 Changchun, China.

School of Artificial Intelligence, Jilin University, 130012 Changchun, China.

出版信息

Brief Bioinform. 2023 Sep 20;24(5). doi: 10.1093/bib/bbad276.

Abstract

MOTIVATION

Identifying the relationships among long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and diseases is highly valuable for diagnosing, preventing, treating and prognosing diseases. The development of effective computational prediction methods can reduce experimental costs. While numerous methods have been proposed, they often to treat the prediction of lncRNA-disease associations (LDAs), miRNA-disease associations (MDAs) and lncRNA-miRNA interactions (LMIs) as separate task. Models capable of predicting all three relationships simultaneously remain relatively scarce. Our aim is to perform multi-task predictions, which not only construct a unified framework, but also facilitate mutual complementarity of information among lncRNAs, miRNAs and diseases.

RESULTS

In this work, we propose a novel unsupervised embedding method called graph contrastive learning for multi-task prediction (GCLMTP). Our approach aims to predict LDAs, MDAs and LMIs by simultaneously extracting embedding representations of lncRNAs, miRNAs and diseases. To achieve this, we first construct a triple-layer lncRNA-miRNA-disease heterogeneous graph (LMDHG) that integrates the complex relationships between these entities based on their similarities and correlations. Next, we employ an unsupervised embedding model based on graph contrastive learning to extract potential topological feature of lncRNAs, miRNAs and diseases from the LMDHG. The graph contrastive learning leverages graph convolutional network architectures to maximize the mutual information between patch representations and corresponding high-level summaries of the LMDHG. Subsequently, for the three prediction tasks, multiple classifiers are explored to predict LDA, MDA and LMI scores. Comprehensive experiments are conducted on two datasets (from older and newer versions of the database, respectively). The results show that GCLMTP outperforms other state-of-the-art methods for the disease-related lncRNA and miRNA prediction tasks. Additionally, case studies on two datasets further demonstrate the ability of GCLMTP to accurately discover new associations. To ensure reproducibility of this work, we have made the datasets and source code publicly available at https://github.com/sheng-n/GCLMTP.

摘要

动机

鉴定长链非编码 RNA(lncRNA)、microRNA(miRNA)和疾病之间的关系对于疾病的诊断、预防、治疗和预后具有重要价值。开发有效的计算预测方法可以降低实验成本。尽管已经提出了许多方法,但它们通常将 lncRNA-疾病关联(LDAs)、miRNA-疾病关联(MDAs)和 lncRNA-miRNA 相互作用(LMIs)的预测视为单独的任务。能够同时预测这三种关系的模型仍然相对较少。我们的目标是进行多任务预测,这不仅构建了一个统一的框架,而且促进了 lncRNA、miRNA 和疾病之间的信息相互补充。

结果

在这项工作中,我们提出了一种新的无监督嵌入方法,称为用于多任务预测的图对比学习(Graph Contrastive Learning for Multi-task Prediction,GCLMTP)。我们的方法旨在通过同时提取 lncRNA、miRNA 和疾病的嵌入表示来预测 LDAs、MDAs 和 LMIs。为此,我们首先构建了一个三层 lncRNA-miRNA-疾病异质图(LMDHG),该图基于它们的相似性和相关性,整合了这些实体之间的复杂关系。接下来,我们使用基于图对比学习的无监督嵌入模型,从 LMDHG 中提取 lncRNA、miRNA 和疾病的潜在拓扑特征。图对比学习利用图卷积网络架构,最大化补丁表示与 LMDHG 的相应高级摘要之间的互信息。随后,对于三个预测任务,我们探索了多个分类器来预测 LDA、MDA 和 LMI 分数。我们在两个数据集(分别来自数据库的旧版本和新版本)上进行了综合实验。结果表明,GCLMTP 在疾病相关 lncRNA 和 miRNA 预测任务中优于其他最先进的方法。此外,两个数据集上的案例研究进一步证明了 GCLMTP 准确发现新关联的能力。为了确保这项工作的可重复性,我们已经在 https://github.com/sheng-n/GCLMTP 上公开了数据集和源代码。

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