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多组学分析结合文本挖掘鉴定复发性心血管事件的新型生物标志物候选物。

Multiomics Analysis Coupled with Text Mining Identify Novel Biomarker Candidates for Recurrent Cardiovascular Events.

机构信息

Department of Pharmacy, School of Health Sciences, University of Patras, Patras, Greece.

Unit of Special Laboratory Diagnostics, University Children's Hospital, UMC, Ljubljana, Slovenia.

出版信息

OMICS. 2020 Apr;24(4):205-215. doi: 10.1089/omi.2019.0216. Epub 2020 Mar 13.

Abstract

Recurrent cardiovascular events remain an enigma that accounts for >30% of deaths worldwide. While heredity and human genetics variation play a key role, host-environment interactions offer a sound conceptual framework to dissect the molecular basis of recurrent cardiovascular events from genes and proteins to metabolites, thus accounting for environmental contributions as well. We report here a multiomics systems science approach so as to map interindividual variability in susceptibility to recurrent cardiovascular events. First, we performed data and text mining through a mixed-methods content analysis to select genomic variants, 10 single nucleotide polymorphisms, and microRNAs (miR-10a, miR-21, and miR-20a), minimizing bias in candidate marker selection. Next, we validated our data in a patient cohort suffering from recurrent cardiovascular events (a cross-sectional study design and sampling). Our findings report a key role in low-density lipoprotein clearance for rs11206510 ( < 0.01) and rs515135 ( < 0.05). miR-10a ( < 0.05) was significantly associated with heart failure, while increased expression levels for miR-21 and miR-20a associated with atherosclerosis. In addition, liquid chromatography-mass spectrometry-based (LC-MS-based) proteomics analyses identified that vascular diameter and cholesterol levels are among the key factors to be considered in recurrent cardiovascular events. From a methodology innovation standpoint, this study offers a strategy to enhance the signal-to-noise ratios in mapping novel biomarker candidates wherein each research and conceptual step were interrogated for their validity and in turn, enriched one another, ideally translating information growth to knowledge growth.

摘要

复发性心血管事件仍然是一个谜,占全球死亡人数的>30%。虽然遗传和人类遗传变异起着关键作用,但宿主-环境相互作用提供了一个合理的概念框架,可将复发性心血管事件的分子基础从基因和蛋白质解析到代谢物,从而解释环境的贡献。我们在此报告一种多组学系统科学方法,以绘制个体对复发性心血管事件易感性的个体间变异性。首先,我们通过混合方法内容分析进行数据和文本挖掘,以选择基因组变异、10 个单核苷酸多态性和 microRNAs(miR-10a、miR-21 和 miR-20a),从而最小化候选标记选择中的偏倚。接下来,我们在患有复发性心血管事件的患者队列中验证了我们的数据(横断面研究设计和采样)。我们的研究结果报告了 rs11206510(<0.01)和 rs515135(<0.05)在低密度脂蛋白清除中的关键作用。miR-10a(<0.05)与心力衰竭显着相关,而 miR-21 和 miR-20a 的表达水平升高与动脉粥样硬化有关。此外,基于液相色谱-质谱(LC-MS)的蛋白质组学分析确定血管直径和胆固醇水平是复发性心血管事件中需要考虑的关键因素之一。从方法学创新的角度来看,本研究提供了一种策略,可增强新型生物标志物候选物映射中的信号与噪声比,其中每个研究和概念步骤都经过有效性的检查,进而相互丰富,理想情况下将信息增长转化为知识增长。

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