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HOPEXGB:一种基于异质疾病-miRNA-lncRNA 信息网络的 miRNA/lncRNA-疾病关联预测共识模型。

HOPEXGB: A Consensual Model for Predicting miRNA/lncRNA-Disease Associations Using a Heterogeneous Disease-miRNA-lncRNA Information Network.

机构信息

College of Chemistry, Sichuan University, Chengdu 610064, China.

出版信息

J Chem Inf Model. 2024 Apr 8;64(7):2863-2877. doi: 10.1021/acs.jcim.3c00856. Epub 2023 Aug 21.

Abstract

Predicting disease-related microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) is crucial to find new biomarkers for the prevention, diagnosis, and treatment of complex human diseases. Computational predictions for miRNA/lncRNA-disease associations are of great practical significance, since traditional experimental detection is expensive and time-consuming. In this paper, we proposed a consensual machine-learning technique-based prediction approach to identify disease-related miRNAs and lncRNAs by high-order proximity preserved embedding (HOPE) and eXtreme Gradient Boosting (XGB), named HOPEXGB. By connecting lncRNA, miRNA, and disease nodes based on their correlations and relationships, we first created a heterogeneous disease-miRNA-lncRNA (DML) information network to achieve an effective fusion of information on similarities, correlations, and interactions among miRNAs, lncRNAs, and diseases. In addition, a more rational negative data set was generated based on the similarities of unknown associations with the known ones, so as to effectively reduce the false negative rate in the data set for model construction. By 10-fold cross-validation, HOPE shows better performance than other graph embedding methods. The final consensual HOPEXGB model yields robust performance with a mean prediction accuracy of 0.9569 and also demonstrates high sensitivity and specificity advantages compared to lncRNA/miRNA-specific predictions. Moreover, it is superior to other existing methods and gives promising performance on the external testing data, indicating that integrating the information on lncRNA-miRNA interactions and the similarities of lncRNAs/miRNAs is beneficial for improving the prediction performance of the model. Finally, case studies on lung, stomach, and breast cancers indicate that HOPEXGB could be a powerful tool for preclinical biomarker detection and bioexperiment preliminary screening for the diagnosis and prognosis of cancers. HOPEXGB is publicly available at https://github.com/airpamper/HOPEXGB.

摘要

预测与疾病相关的 microRNAs(miRNAs)和长链非编码 RNA(lncRNAs)对于寻找预防、诊断和治疗复杂人类疾病的新生物标志物至关重要。通过高次近邻保留嵌入(HOPE)和极端梯度提升(XGB)的共识机器学习技术预测 miRNA/lncRNA-疾病关联具有重要的实际意义,因为传统的实验检测既昂贵又耗时。在本文中,我们提出了一种基于共识机器学习技术的预测方法,通过高次近邻保留嵌入(HOPE)和极端梯度提升(XGB),即 HOPEXGB,来识别与疾病相关的 miRNA 和 lncRNA。通过基于相关性和关系连接 lncRNA、miRNA 和疾病节点,我们首先创建了一个异质疾病-miRNA-lncRNA(DML)信息网络,以实现 miRNA、lncRNA 和疾病之间相似性、相关性和相互作用信息的有效融合。此外,基于未知关联与已知关联的相似性生成了一个更合理的负数据集,以有效降低模型构建中数据集中的假阴性率。通过 10 折交叉验证,HOPE 表现优于其他图嵌入方法。最终的共识 HOPEXGB 模型具有稳健的性能,平均预测准确率为 0.9569,与 lncRNA/miRNA 特异性预测相比,还具有较高的敏感性和特异性优势。此外,它优于其他现有方法,并在外部测试数据上表现出有前途的性能,这表明整合 lncRNA-miRNA 相互作用信息和 lncRNA/miRNA 的相似性有助于提高模型的预测性能。最后,对肺癌、胃癌和乳腺癌的案例研究表明,HOPEXGB 可能是一种强大的工具,可用于癌症的临床前生物标志物检测和生物实验初步筛选,以诊断和预测癌症。HOPEXGB 可在 https://github.com/airpamper/HOPEXGB 上公开获取。

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