Pilot analysis of the plasma metabolite profiles associated with emphysematous Chronic Obstructive Pulmonary Disease phenotype

Pilot analysis of the plasma metabolite profiles associated with emphysematous Chronic Obstructive Pulmonary Disease phenotype
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DOI:
10.1016/j.bbrc.2011.09.006
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发表时间:
2011-10-07
影响因子:
3.1
通讯作者:
Shim, Y. Michael
Shim, Y. Michael
中科院分区:
生物学4区
文献类型:
--
作者:
Paige, Mikell;Burdick, Marie D.;Shim, Y. Michael

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目前的初步研究检验了这样一种假设,即与那些没有发展成慢性阻塞性肺疾病(COPD)肺气肿表型的吸烟者相比,吸烟者在其相应的代谢组学谱中具有独特的模式。从38名具有不同表型的COPD受试者收集外周血血浆样品。他们被分为三组:健康的非吸烟者(n = 16),吸烟者没有肺气肿(n = 8),吸烟者肺气肿(n = 14)。采用超高效液相色谱/四极杆飞行时间质谱技术鉴别大量代谢物标志物(3534)。无监督聚类分析准确地将吸烟者与非吸烟者区分开来,并展示了代谢组学数据的潜力。随后,使用监督学习集创建预测模型,发现这些预测模型在识别具有COPD肺气肿表型的受试者方面高度准确,具有出色的灵敏度和特异性。我们的方法提供了一个初步的模型,区分肺气肿COPD表型从其他COPD表型的基础上的代谢组学概况。这些结果还表明,代谢组学分析可能潜在地指导导致肺气肿性COPD表型的相关代谢物的表征。爱思唯尔公司出版
The current pilot study examined the hypothesis that cigarette smokers who developed an emphysematous phenotype of Chronic Obstructive Pulmonary Disease (COPD) were associated with distinctive patterns in their corresponding metabolomics profile as compared to those who did not. Peripheral blood plasma samples were collected from 38 subjects with different phenotypes of COPD. They were categorized into three groups: healthy non-smokers (n = 16), smokers without emphysema (n = 8), and smokers with emphysema (n = 14). Ultra High Performance Liquid Chromatography/quadrupole-Time-of-Flight Mass Spectrometry techniques were used to identify a large number of metabolite markers (3534). Unsupervised clustering analysis accurately separated the smokers with emphysema from others without emphysema and demonstrated potentials of this metabolomics data. Subsequently predictive models were created with a supervised learning set, and these predictive models were found to be highly accurate in identifying the subjects with the emphysematous phenotype of COPD with excellent sensitivity and specificity. Our methodology provides a preliminary model that differentiates an emphysematous COPD phenotype from other COPD phenotypes on the basis of the metabolomics profiles. These results also suggest that the metabolomics profiling could potentially guide the characterization of relevant metabolites that leads to an emphysematous COPD phenotype. Published by Elsevier Inc.