title: eRah: A Computational Tool Integrating Spectral Deconvolution and Alignment with Quantification and Identification of Metabolites in GC/MS-Based Metabolomics.
abstract: 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-EI 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), (iii) 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 (TOF) 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, LC-QqQ, and NMR. eRah is freely available at http://CRAN.R-project.org/package=erah .
authors: Metabolomics Platform, Department of Electronic Engineering (DEEEA), Universitat Rovira i Virgili , 43003 Tarragona, Catalonia, Spain.|Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) , 28029 Madrid, Spain.
authors: Xavier
authors: X
authors: Domingo-Almenara
authors: Metabolomics Platform, Department of Electronic Engineering (DEEEA), Universitat Rovira i Virgili , 43003 Tarragona, Catalonia, Spain.|Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) , 28029 Madrid, Spain.
authors: Jesus
authors: J
authors: Brezmes
authors: Metabolomics Platform, Department of Electronic Engineering (DEEEA), Universitat Rovira i Virgili , 43003 Tarragona, Catalonia, Spain.|Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) , 28029 Madrid, Spain.
authors: Maria
authors: M
authors: Vinaixa
authors: Metabolomics Platform, Department of Electronic Engineering (DEEEA), Universitat Rovira i Virgili , 43003 Tarragona, Catalonia, Spain.|Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) , 28029 Madrid, Spain.
authors: Sara
authors: S
authors: Samino
authors: Metabolomics Platform, Department of Electronic Engineering (DEEEA), Universitat Rovira i Virgili , 43003 Tarragona, Catalonia, Spain.|Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) , 28029 Madrid, Spain.
authors: Noelia
authors: N
authors: Ramirez
authors: Institut de Recerca Pediàtrica, Hospital Sant Joan de Déu, University of Barcelona , 08950 Barcelona, Catalonia, Spain.
authors: Marta
authors: M
authors: Ramon-Krauel
authors: Institut de Recerca Pediàtrica, Hospital Sant Joan de Déu, University of Barcelona , 08950 Barcelona, Catalonia, Spain.
authors: Carles
authors: C
authors: Lerin
authors: Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) , 28029 Madrid, Spain.|Institut de Recerca Pediàtrica, Hospital Sant Joan de Déu, University of Barcelona , 08950 Barcelona, Catalonia, Spain.
authors: Marta
authors: M
authors: Díaz
authors: Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) , 28029 Madrid, Spain.|Institut de Recerca Pediàtrica, Hospital Sant Joan de Déu, University of Barcelona , 08950 Barcelona, Catalonia, Spain.
authors: Lourdes
authors: L
authors: Ibáñez
authors: Metabolomics Platform, Department of Electronic Engineering (DEEEA), Universitat Rovira i Virgili , 43003 Tarragona, Catalonia, Spain.|Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) , 28029 Madrid, Spain.
authors: Xavier
authors: X
authors: Correig
authors: B2SLab, Center for Biomedical Engineering Research (CREB), CIBERBBN, Department of ESAII, Universitat Politècnica de Catalunya , 08028 Barcelona, Catalonia, Spain.
authors: Alexandre
authors: A
authors: Perera-Lluna
authors: Metabolomics Platform, Department of Electronic Engineering (DEEEA), Universitat Rovira i Virgili , 43003 Tarragona, Catalonia, Spain.|Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) , 28029 Madrid, Spain.
authors: Oscar
authors: O
authors: Yanes
mesh_terms: D000293:Adolescent; D000465:Algorithms; D000728:Androgens / Q000097:blood*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood*; D055432:Metabolomics; D015999:Multivariate Analysis; D012984:Software
chemical_list: D000728:Androgens