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The importance of experimental design and QC samples in large-scale and MS-driven untargeted metabolomic studies of humans

    Warwick B Dunn

    * Author for correspondence

    Centre for Advanced Discovery & Experimental Therapeutics, Institute of Human Development, University of Manchester & Manchester Academic Health Sciences Centre, Central Manchester NHS Foundation Trust, York Place, Oxford Road, Manchester, M13 9WL, UK.

    ,
    Ian D Wilson

    Biomolecular Medicine, Department of Surgery & Cancer, Faculty of Medicine, Sir Alexander Fleming Building, Imperial College London, London, SW7 2AZ, UK

    ,
    Andrew W Nicholls

    Investigative Preclinical Toxicology, GlaxoSmithKline, David Jack Centre for Research and Development, Park Road, Ware, Hertfordshire, SG12 0DP, UK

    &
    David Broadhurst

    Department of Medicine, Katz Group Centre for Pharmacy & Health, University of Alberta, Edmonton, Alberta, Canada

    Published Online:https://doi.org/10.4155/bio.12.204

    The metabolic investigation of the human population is becoming increasingly important in the study of health and disease. The phenotypic variation can be investigated through the application of metabolomics; to provide a statistically robust investigation, the study of hundreds to thousands of individuals is required. In untargeted and MS-focused metabolomic studies this once provided significant hurdles. However, recent innovations have enabled the application of MS platforms in large-scale, untargeted studies of humans. Herein we describe the importance of experimental design, the separation of the biological study into multiple analytical experiments and the incorporation of QC samples to provide the ability to perform signal correction in order to reduce analytical variation and to quantitatively determine analytical precision. In addition, we describe how to apply this in quality assurance processes. These innovations have opened up the capabilities to perform routine, large-scale, untargeted, MS-focused studies.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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