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基于代谢组学和临床特征整合的慢性阻塞性肺疾病表型分析。

Phenotyping of Chronic Obstructive Pulmonary Disease Based on the Integration of Metabolomes and Clinical Characteristics.

机构信息

Department of Biochemistry, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, Estonia.

Centre of Excellence for Genomics and Translational Medicine, Riia 23b, 51010 Tartu, Estonia.

出版信息

Int J Mol Sci. 2018 Feb 27;19(3):666. doi: 10.3390/ijms19030666.

Abstract

Apart from the refined management-oriented clinical stratification of chronic obstructive pulmonary disease (COPD), the molecular pathologies behind this highly prevalent disease have remained obscure. The aim of this study was the characterization of patients with COPD, based on the metabolomic profiling of peripheral blood and exhaled breath condensate (EBC) within the context of defined clinical and demographic variables. Mass-spectrometry-based targeted analysis of serum metabolites (mainly amino acids and lipid species), untargeted profiles of serum and EBC of patients with COPD of different clinical characteristics ( = 25) and control individuals ( = 21) were performed. From the combined clinical/demographic and metabolomics data, associations between clinical/demographic and metabolic parameters were searched and a de novo phenotyping for COPD was attempted. Adjoining the clinical parameters, sphingomyelins were the best to differentiate COPD patients from controls. Unsaturated fatty acid-containing lipids, ornithine metabolism and plasma protein composition-associated signals from the untargeted analysis differentiated the Global Initiative for COPD (GOLD) categories. Hierarchical clustering did not reveal a clinical-metabolomic stratification superior to the strata set by the GOLD consensus. We conclude that while metabolomics approaches are good for finding biomarkers and clarifying the mechanism of the disease, there are no distinct co-variate independent clinical-metabolic phenotypes.

摘要

除了对慢性阻塞性肺疾病(COPD)进行精细化的管理导向的临床分层外,这种高发性疾病背后的分子病理学仍然不清楚。本研究的目的是根据外周血和呼出气冷凝物(EBC)的代谢组学特征,对 COPD 患者进行特征描述,同时考虑到特定的临床和人口统计学变量。通过基于质谱的靶向分析,对不同临床特征(= 25)和对照个体(= 21)的 COPD 患者的血清代谢物(主要为氨基酸和脂质种类)、血清和 EBC 的非靶向谱进行了检测。从综合的临床/人口统计学和代谢组学数据中,寻找了临床/人口统计学和代谢参数之间的关联,并尝试对 COPD 进行新的表型分析。除了临床参数外,神经鞘磷脂是区分 COPD 患者和对照组的最佳标志物。来自非靶向分析的不饱和脂肪酸含量的脂质、精氨酸代谢和血浆蛋白组成相关信号可区分慢性阻塞性肺疾病全球倡议(GOLD)的类别。分层聚类并没有揭示出一种优于 GOLD 共识所设定的临床代谢分层的方法。我们得出结论,虽然代谢组学方法在寻找生物标志物和阐明疾病机制方面表现良好,但并没有明显的与协变量无关的临床代谢表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a452/5877527/fc2e8b71ab27/ijms-19-00666-g001.jpg

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