eRah: A Computational Tool Integrating Spectral Deconvolution and Alignment with Quantification and Identification of Metabolites in GC/MS-Based Metabolomics
eRah: A Computational Tool Integrating Spectral Deconvolution and Alignment with Quantification and Identification of Metabolites in GC/MS-Based Metabolomics
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DOI：
10.1021/acs.analchem.6b02927
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发表时间：
2016-10-04
影响因子：
7.4
通讯作者：
Yanes, Oscar
中科院分区：
文献类型：
--
作者：
Domingo-Almenara, Xavier;Brezmes, Jesus;Yanes, Oscar
由于电子碰撞电离（EI）的高度可重复的电离过程，气相色谱-质谱联用（GC/MS）一直是用于鉴定小分子的长期方法。然而，在非靶向代谢组学中使用GC-BI MS会产生大量复杂的数据集，其特征在于共洗脱化合物和由硬电子电离引起的分子离子的广泛碎片化。为了识别和提取多个生物样品中代谢物的定量信息，需要集成的数据处理计算工作流程：在这里，我们介绍了eRah，一个用开放语言R编写的免费计算工具，由五个核心功能组成：（i）GC/MS色谱图的噪声过滤和基线去除，（ii）使用基于局部协方差化合物匹配（CMLC）和正交信号去卷积（OSD）的多变量分析技术的创新化合物去卷积过程，样品间质谱的对齐，（iv）缺失化合物回收，和（v）使用公开可用的质谱通过光谱库匹配鉴定代谢物。eRah输出一个包含化合物名称、匹配分数和每个样品化合物积分面积的表格。eRah的自动化功能通过以下方式得到证明：分析来自高胰岛素血症雄激素过多青少年和健康对照的血浆样本的GC-飞行时间（TOP）MS数据。eRah的定量结果与centWave、在广泛使用的XCMS包中实现的峰值拾取算法、MetAlign和ChromaTOF软件进行了比较。使用纯标准品和通过GC-三重四极杆（QqQ）MS、LG-QqQ和NMR的靶向分析进一步验证显著失调的代谢物。eRah可在http://CRAN.R-project.org/package=erah=erah上免费获取。
Gas chromatography coupled to mass spectrometry (GC/MS) has been a long-standing approach used for identifying small molecules due to the highly reproducible ionization process of electron impact ionization (EI). However, the use of GC-BI MS in untargeted metabolomics produces large and complex data sets characterized by coeluting compounds and extensive fragmentation of molecular ions caused by the hard electron ionization. In order to identify and extract quantitative information on metabolites across multiple biological, samples, integrated computational workflows for data processing are needed: Here we introduce eRah, a free computational tool written in the open language R composed of five core functions: (i) noise filtering and baseline removal of GC/MS chromatograms, (ii) an innovative compound deconvolution process using multivariate analysis techniques based on compound match by local covariance (CMLC) and orthogonal signal deconvolution (OSD), alignment of mass spectra across samples, (iv) missing Compound recovery, and (v) identification of metabolites by spectral library matching using publicly available mass spectra. eRah Outputs a table with compound names,, matching scores and the integrated area of compounds for each sample. The automated capabilities of eRah are demonstrated by: the analysis of GC-time-of-flight (TOP) MS data from plasma samples of adolescents with hyperinsulinaemic androgen excess and healthy controls. The quantitative results of eRah are compared to centWave, the Peak-picking algorithm implemented in the widely used XCMS package, MetAlign, and ChromaTOF software. Significantly dysregulated metabolites are further validated using pure standards and targeted analysis by GC-triple quadrupole (QqQ) MS, LG-QqQ, and NMR. eRah is freely available at http://CRAN.R-project.org/package=erah=erah.