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验证帕金森病中的差异挥发组图谱

Validating Differential Volatilome Profiles in Parkinson's Disease.

作者信息

Sinclair Eleanor, Walton-Doyle Caitlin, Sarkar Depanjan, Hollywood Katherine A, Milne Joy, Lim Sze Hway, Kunath Tilo, Rijs Anouk M, de Bie Rob M A, Silverdale Monty, Trivedi Drupad K, Barran Perdita

机构信息

Manchester Institute of Biotechnology, School of Chemistry, The University of Manchester, Princess Street, Manchester M1 7DN, United Kingdom.

Manchester Centre for Synthetic Biology of Fine and Speciality Chemicals (SYNBIOCHEM), Manchester Institute of Biotechnology, School of Chemistry, The University of Manchester, Princess Street, Manchester M1 7DN, United Kingdom.

出版信息

ACS Cent Sci. 2021 Feb 24;7(2):300-306. doi: 10.1021/acscentsci.0c01028. Epub 2021 Feb 12.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder that does not currently have a robust clinical diagnostic test. Nonmotor symptoms such as skin disorders have long since been associated with the disease, and more recently a characteristic odor emanating from the skin of people with Parkinson's has been identified. Here, dynamic head space (DHS) thermal desorption (TD) gas chromatography-mass spectrometry (GC-MS) is implemented to directly measure the volatile components of sebum on swabs sampled from people with Parkinson's-both drug naïve and those on PD medications ( = 100) and control subjects ( = 29). Supervised multivariate analyses of data showed 84.4% correct classification of PD cases using all detected volatile compounds. Variable importance in projection (VIP) scores were generated from these data, which revealed eight features with VIP > 1 and < 0.05 which all presented a downregulation within the control cohorts. Purified standards based on previously annotated analytes of interest eicosane and octadecanal did not match to patient sample data, although multiple metabolite features are annotated with these compounds all with high spectral matches indicating the presence of a series of similar structured species. DHS-TD-GC-MS analysis of a range of lipid standards has revealed the presence of common hydrocarbon species rather than differentiated intact compounds which are hypothesized to be breakdown products of lipids. This replication study validates that a differential volatile profile between control and PD cohorts can be measured using an analytical method that measures volatile compounds directly from skin swabs.

摘要

帕金森病(PD)是一种进行性神经退行性疾病,目前尚无可靠的临床诊断测试。诸如皮肤疾病等非运动症状长期以来一直与该疾病相关,最近还发现帕金森病患者皮肤散发出一种特殊气味。在此,采用动态顶空(DHS)热脱附(TD)气相色谱 - 质谱联用(GC - MS)技术,直接测量从帕金森病患者(包括未服用药物的初治患者和正在服用帕金森病药物的患者,共100例)以及对照受试者(29例)的拭子样本中采集的皮脂挥发性成分。对数据进行的监督多变量分析显示,使用所有检测到的挥发性化合物,帕金森病病例的正确分类率为84.4%。从这些数据中生成了投影变量重要性(VIP)得分,结果显示有8个VIP>1且P<0.05的特征,这些特征在对照队列中均呈现下调。基于先前注释的目标分析物二十烷和十八醛的纯化标准品与患者样本数据不匹配,尽管多个代谢物特征被注释为这些化合物,且所有这些特征都具有高光谱匹配度,表明存在一系列结构相似的物种。对一系列脂质标准品进行DHS - TD - GC - MS分析发现,存在常见的烃类物质,而非不同的完整化合物,推测这些烃类物质是脂质的分解产物。这项重复性研究证实,通过一种直接从皮肤拭子测量挥发性化合物的分析方法,可以检测出对照队列和帕金森病队列之间不同的挥发性特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30bb/7908024/68c7273ea9df/oc0c01028_0001.jpg

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