title: SMART: Statistical Metabolomics Analysis-An R Tool.
abstract: Metabolomics data provide unprecedented opportunities to decipher metabolic mechanisms by analyzing hundreds to thousands of metabolites. Data quality concerns and complex batch effects in metabolomics must be appropriately addressed through statistical analysis. This study developed an integrated analysis tool for metabolomics studies to streamline the complete analysis flow from initial data preprocessing to downstream association analysis. We developed Statistical Metabolomics Analysis-An R Tool (SMART), which can analyze input files with different formats, visually represent various types of data features, implement peak alignment and annotation, conduct quality control for samples and peaks, explore batch effects, and perform association analysis. A pharmacometabolomics study of antihypertensive medication was conducted and data were analyzed using SMART. Neuromedin N was identified as a metabolite significantly associated with angiotensin-converting-enzyme inhibitors in our metabolome-wide association analysis (p = 1.56 × 10(-4) in an analysis of covariance (ANCOVA) with an adjustment for unknown latent groups and p = 1.02 × 10(-4) in an ANCOVA with an adjustment for hidden substructures). This endogenous neuropeptide is highly related to neurotensin and neuromedin U, which are involved in blood pressure regulation and smooth muscle contraction. The SMART software, a user guide, and example data can be downloaded from http://www.stat.sinica.edu.tw/hsinchou/metabolomics/SMART.htm .
authors.affiliation: Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University , Taipei 10617, Taiwan.|Institute of Statistical Science, Academia Sinica , Taipei 115, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Liang
authors.affiliation: Institute of Statistical Science, Academia Sinica , Taipei 115, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Lin
authors.affiliation: Institute of Statistical Science, Academia Sinica , Taipei 115, Taiwan.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Chen
authors.affiliation: Institute of Statistical Science, Academia Sinica , Taipei 115, Taiwan.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Lin
authors.affiliation: Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University , Taipei 10617, Taiwan.|Department of Computer Science and Information Engineering, National Taiwan University , Taipei 10617, Taiwan.
authors.forename: Kun-Mao
authors.initials: KM
authors.lastname: Chao
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica , Taipei 115, Taiwan.
authors.forename: Wen-Harn
authors.initials: WH
authors.lastname: Pan
authors.affiliation: Institute of Statistical Science, Academia Sinica , Taipei 115, Taiwan.|Institute of Public Health, National Yang Ming University , Taipei 11221, Taiwan.|Department of Statistics, National Cheng Kung University , Tainan 701, Taiwan.|Institute of Statistics, National Tsing Hua University , Hsinchu 30013, Taiwan.|School of Public Health, National Defense Medical Center , Taipei 114, Taiwan.
authors.forename: Hsin-Chou
authors.initials: HC
authors.lastname: Yang
mesh_terms: D000704:Analysis of Variance; D008401:Gas Chromatography-Mass Spectrometry; D020407:Internet; D055432:Metabolomics; D009496:Neurotensin / Q000032:analysis; D010446:Peptide Fragments / Q000032:analysis; D012083:Renin / Q000378:metabolism; D014584:User-Computer Interface; D000092502:Renin Inhibitors
chemical_list: D009496:Neurotensin; D010446:Peptide Fragments; D012083:Renin; D000092502:Renin Inhibitors; C042090:neuromedin N