Precision of a Clinical Metabolomics Profiling Platform for Use in the Identification of Inborn Errors of Metabolism
Precision of a Clinical Metabolomics Profiling Platform for Use in the Identification of Inborn Errors of Metabolism
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DOI：
10.1093/jalm/jfz026
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发表时间：
2020-03-01
影响因子：
2
通讯作者：
Toal, Douglas R.
中科院分区：
文献类型：
--
作者：
Ford, Lisa;Kennedy, Adam D.;Toal, Douglas R.
背景资料：全外显子组测序在遗传病诊断中的应用为临床实验室中基于系统的方法铺平了道路。在这里，我们描述了一种临床代谢组学方法，通过多管齐下的质谱平台的分析，代谢疾病的筛选。通过同时测量单个样本中的数百种代谢物，临床代谢组学提供了一种全面的方法来识别多个生化途径中的代谢扰动。方法：我们在4个多臂高通量代谢组学平台上对人体血浆中的数百种代谢物进行了一天和多日的精密度研究。结果：4个平台的平均实验室变异系数（CV）在9.3%-11.5%之间（中位数，6.5-8.4%），4个平台的平均试验间CV范围为9.9 - 12.6%（中位数，7.0-8.3%），4个平台的平均试验内CV范围为5.7 - 6.9%（中位数，3.5-4.4%）。关于患者样本检测，与IEM疾病相关的多种生物标志物的精密度显示，4个分析批次的CV范围为0.2 - 11.0%。该评价描述了4个相同代谢组学平台的单日和多日精密度，每个平台由4个独立方法组组成，和多个分析批次中患者样本中关键IEM代谢物测量方法的重现性，提供证据表明，该方法对于筛查患有先天性代谢缺陷的患者是稳健的和可重复的。
Background: The application of whole-exome sequencing for the diagnosis of genetic disease has paved the way for systems-based approaches in the clinical laboratory. Here, we describe a clinical metabolomics method for the screening of metabolic diseases through the analysis of a multi-pronged mass spectrometry platform. By simultaneously measuring hundreds of metabolites in a single sample, clinical metabolomics offers a comprehensive approach to identify metabolic perturbations across multiple biochemical pathways.Methods: We conducted a single- and multi-day precision study on hundreds of metabolites in human plasma on 4, multi-arm, high-throughput metabolomics platforms.Results: The average laboratory coefficient of variation (CV) on the 4 platforms was between 9.3 and 11.5% (median, 6.5-8.4%), average inter-assay CV on the 4 platforms ranged from 9.9 to 12.6% (median, 7.0-8.3%) and average intra-assay CV on the 4 platforms ranged from 5.7 to 6.9% (median, 3.5-4.4%). In relation to patient sample testing, the precision of multiple biomarkers associated with IEM disorders showed CVs that ranged from 0.2 to 11.0% across 4 analytical batches.Conclusions: This evaluation describes single and multi-day precision across 4 identical metabolomics platforms, comprised each of 4 independent method arms, and reproducibility of the method for the measurement of key IEM metabolites in patient samples across multiple analytical batches, providing evidence that the method is robust and reproducible for the screening of patients with inborn errors of metabolism.