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决策树集成揭示潜在的 miRNA-疾病关联。

Ensemble of decision tree reveals potential miRNA-disease associations.

机构信息

School of Information and Control Engineering, China University of Mining and Technology, Xuzhou, China.

出版信息

PLoS Comput Biol. 2019 Jul 22;15(7):e1007209. doi: 10.1371/journal.pcbi.1007209. eCollection 2019 Jul.

DOI:10.1371/journal.pcbi.1007209
PMID:31329575
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6675125/
Abstract

In recent years, increasing associations between microRNAs (miRNAs) and human diseases have been identified. Based on accumulating biological data, many computational models for potential miRNA-disease associations inference have been developed, which saves time and expenditure on experimental studies, making great contributions to researching molecular mechanism of human diseases and developing new drugs for disease treatment. In this paper, we proposed a novel computational method named Ensemble of Decision Tree based MiRNA-Disease Association prediction (EDTMDA), which innovatively built a computational framework integrating ensemble learning and dimensionality reduction. For each miRNA-disease pair, the feature vector was extracted by calculating the statistical measures, graph theoretical measures, and matrix factorization results for the miRNA and disease, respectively. Then multiple base learnings were built to yield many decision trees (DTs) based on random selection of negative samples and miRNA/disease features. Particularly, Principal Components Analysis was applied to each base learning to reduce feature dimensionality and hence remove the noise or redundancy. Average strategy was adopted for these DTs to get final association scores between miRNAs and diseases. In model performance evaluation, EDTMDA showed AUC of 0.9309 in global leave-one-out cross validation (LOOCV) and AUC of 0.8524 in local LOOCV. Additionally, AUC of 0.9192+/-0.0009 in 5-fold cross validation proved the model's reliability and stability. Furthermore, three types of case studies for four human diseases were implemented. As a result, 94% (Esophageal Neoplasms), 86% (Kidney Neoplasms), 96% (Breast Neoplasms) and 88% (Carcinoma Hepatocellular) of top 50 predicted miRNAs were confirmed by experimental evidences in literature.

摘要

近年来,越来越多的研究表明 microRNAs(miRNAs)与人类疾病之间存在关联。基于不断积累的生物学数据,已经开发出许多用于预测潜在 miRNA-疾病关联的计算模型,这为研究人类疾病的分子机制和开发治疗疾病的新药节省了实验研究的时间和费用,做出了巨大贡献。在本文中,我们提出了一种名为基于集成决策树的 miRNA-疾病关联预测(EDTMDA)的新计算方法,该方法创新性地构建了一个集成了集成学习和降维的计算框架。对于每个 miRNA-疾病对,通过计算 miRNA 和疾病的统计度量、图论度量和矩阵分解结果,提取特征向量。然后,基于随机选择负样本和 miRNA/疾病特征,构建多个基础学习来生成多个决策树(DTs)。特别地,对每个基础学习应用主成分分析来降低特征维度,从而去除噪声或冗余。采用平均策略对这些 DTs 进行处理,以获得 miRNA 和疾病之间的最终关联得分。在模型性能评估中,EDTMDA 在全局留一交叉验证(LOOCV)中表现出 0.9309 的 AUC,在局部 LOOCV 中表现出 0.8524 的 AUC。此外,在 5 折交叉验证中,AUC 为 0.9192+/-0.0009,证明了模型的可靠性和稳定性。此外,对四种人类疾病进行了三种类型的案例研究。结果表明,文献中实验证据证实了前 50 个预测 miRNA 中 94%(食管癌)、86%(肾肿瘤)、96%(乳腺癌)和 88%(肝细胞癌)的 miRNA。

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