Assessment of coverage for endogenous metabolites and exogenous chemical compounds using an untargeted metabolomics platform
Assessment of coverage for endogenous metabolites and exogenous chemical compounds using an untargeted metabolomics platform
复制标题
使用非靶向代谢组学平台评估内源代谢物和外源化合物的覆盖范围
DOI：
10.1142/9789811215636_0052
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发表时间：
2019
影响因子：
--
通讯作者：
C. Hernández
中科院分区：
文献类型：
--
作者：
S. Kong;C. Hernández
个体的生理状态和病理变化可以通过代谢状态来捕捉，代谢状态反映了遗传变异和环境因素（如饮食、生活方式和肠道微生物群）的影响。整个生命周期的环境暴露总量- -即暴露量- -难以用目前的技术来衡量。然而，外源性化学物质的靶向测量和内源性代谢物的非靶向分析已被广泛用于发现病理生理变化的生物标志物和了解遗传变异的功能影响。为了研究化学空间的覆盖范围以及与人口统计学和病理条件相关的个体间差异，我们使用非靶向代谢组学平台分析了169份血浆样本。平均而言，在我们的队列中检测到的1,244种总化合物中，每个个体（范围906 - 1,038）量化了1,009种代谢物。值得注意的是，在男性和女性中，年龄与检测到的代谢物总数呈正相关。使用稳健的Qn估计器，我们在每个样本中发现代谢物异常值（平均22，范围从7到86）。在一名苯丙酮尿患者中，共有50种代谢物是异常值，其中包括苯丙氨酸途径，表明该患者的多种代谢途径受到干扰。异常值最多（N=86）的是一名因肝硬化而等待肝移植的5岁α -1抗胰蛋白酶缺乏症男孩。包括药物、饮食和环境化学物质在内的外源物与多种内源性代谢物显著相关，抗生素的使用显著改变了宿主循环中检测到的肠道微生物产物。需要解决特征标注、各年龄组和性别特征的参考范围和方差、人口规模参考数据集等问题；然而，非靶向代谢组学可以立即用作生物标志物发现平台，并评估基因组变异和暴露对某些疾病代谢途径的影响。
Physiological status and pathological changes in an individual can be captured by metabolic state that reflects the influence of both genetic variants and environmental factors such as diet, lifestyle and gut microbiome. The totality of environmental exposure throughout lifetime – i.e., exposome – is difficult to measure with current technologies. However, targeted measurement of exogenous chemicals and untargeted profiling of endogenous metabolites have been widely used to discover biomarkers of pathophysiologic changes and to understand functional impacts of genetic variants. To investigate the coverage of chemical space and interindividual variation related to demographic and pathological conditions, we profiled 169 plasma samples using an untargeted metabolomics platform. On average, 1,009 metabolites were quantified in each individual (range 906 – 1,038) out of 1,244 total chemical compounds detected in our cohort. Of note, age was positively correlated with the total number of detected metabolites in both males and females. Using the robust Qn estimator, we found metabolite outliers in each sample (mean 22, range from 7 to 86). A total of 50 metabolites were outliers in a patient with phenylketonuria including the ones known for phenylalanine pathway suggesting multiple metabolic pathways perturbed in this patient. The largest number of outliers (N=86) was found in a 5-year-old boy with alpha-1-antitrypsin deficiency who were waiting for liver transplantation due to cirrhosis. Xenobiotics including drugs, diets and environmental chemicals were significantly correlated with diverse endogenous metabolites and the use of antibiotics significantly changed gut microbial products detected in host circulation. Several challenges such as annotation of features, reference range and variance for each feature per age group and gender, and population scale reference datasets need to be addressed; however, untargeted metabolomics could be immediately deployed as a biomarker discovery platform and to evaluate the impact of genomic variants and exposures on metabolic pathways for some diseases.
影响因子：
20.3
作者：
Weber, Daniela;Oefner, Peter J.;Holler, Ernst
通讯作者：
Holler, Ernst