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DrugPattern 工具用于药物集富集分析及其对 oxLDL 对 2 型糖尿病有益作用的预测。

The DrugPattern tool for drug set enrichment analysis and its prediction for beneficial effects of oxLDL on type 2 diabetes.

机构信息

Department of Biomedical Informatics, Department of Physiology and Pathophysiology, MOE Key Lab of Cardiovascular Sciences, School of Basic Medical Sciences, Center for Non-Coding RNA Medicine, Peking University, Beijing 100191, China; School of Mathematics Sciences, Huaqiao University, Quanzhou 362021, China.

Department of Biomedical Informatics, Department of Physiology and Pathophysiology, MOE Key Lab of Cardiovascular Sciences, School of Basic Medical Sciences, Center for Non-Coding RNA Medicine, Peking University, Beijing 100191, China.

出版信息

J Genet Genomics. 2018 Jul 20;45(7):389-397. doi: 10.1016/j.jgg.2018.07.002. Epub 2018 Jul 24.

Abstract

Enrichment analysis methods, e.g., gene set enrichment analysis, represent one class of important bioinformatical resources for mining patterns in biomedical datasets. However, tools for inferring patterns and rules of a list of drugs are limited. In this study, we developed a web-based tool, DrugPattern, for drug set enrichment analysis. We first collected and curated 7019 drug sets, including indications, adverse reactions, targets, pathways, etc. from public databases. For a list of interested drugs, DrugPattern then evaluates the significance of the enrichment of these drugs in each of the 7019 drug sets. To validate DrugPattern, we employed it for the prediction of the effects of oxidized low-density lipoprotein (oxLDL), a factor expected to be deleterious. We predicted that oxLDL has beneficial effects on some diseases, most of which were supported by evidence in the literature. Because DrugPattern predicted the potential beneficial effects of oxLDL in type 2 diabetes (T2D), animal experiments were then performed to further verify this prediction. As a result, the experimental evidences validated the DrugPattern prediction that oxLDL indeed has beneficial effects on T2D in the case of energy restriction. These data confirmed the prediction accuracy of our approach and revealed unexpected protective roles for oxLDL in various diseases. This study provides a tool to infer patterns and rules in biomedical datasets based on drug set enrichment analysis. DrugPattern is available at http://www.cuilab.cn/drugpattern.

摘要

富集分析方法,例如基因集富集分析,是挖掘生物医学数据集模式的一类重要生物信息学资源。然而,用于推断药物列表的模式和规则的工具是有限的。在本研究中,我们开发了一个基于网络的工具 DrugPattern,用于药物集富集分析。我们首先从公共数据库中收集和整理了 7019 个药物集,包括适应症、不良反应、靶点、通路等。对于感兴趣的药物列表,DrugPattern 然后评估这些药物在 7019 个药物集中的富集的显著性。为了验证 DrugPattern,我们将其用于预测氧化低密度脂蛋白(oxLDL)的作用,oxLDL 是一种预期有害的因子。我们预测 oxLDL 对一些疾病有有益的影响,其中大多数都得到了文献中的证据支持。由于 DrugPattern 预测了 oxLDL 在 2 型糖尿病(T2D)中的潜在有益作用,因此进行了动物实验来进一步验证这一预测。结果,实验证据验证了 DrugPattern 的预测,即在能量限制的情况下,oxLDL 确实对 T2D 有有益的影响。这些数据证实了我们方法的预测准确性,并揭示了 oxLDL 在各种疾病中出人意料的保护作用。本研究提供了一种基于药物集富集分析推断生物医学数据集模式和规则的工具。DrugPattern 可在 http://www.cuilab.cn/drugpattern 上获得。

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