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A robust, single-injection method for targeted, broad-spectrum plasma metabolomics

Discussion in 'Latest ME/CFS Research' started by hixxy, Sep 26, 2017.

  1. hixxy

    hixxy Senior Member

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    Australia
    Metabolomics. 2017;13(10):122. doi: 10.1007/s11306-017-1264-1. Epub 2017 Sep 4.

    A robust, single-injection method for targeted, broad-spectrum plasma metabolomics.

    Li K, Naviaux JC, Bright AT, Wang L, Naviaux RK.

    Abstract

    BACKGROUND:
    Metabolomics is a powerful emerging technology for studying the systems biology and chemistry of health and disease. Current targeted methods are often limited by the number of analytes that can be measured, and/or require multiple injections.

    METHODS:
    We developed a single-injection, targeted broad-spectrum plasma metabolomic method on a SCIEX Qtrap 5500 LC-ESI-MS/MS platform. Analytical validation was conducted for the reproducibility, linearity, carryover and blood collection tube effects. The method was also clinically validated for its potential utility in the diagnosis of chronic fatigue syndrome (CFS) using a cohort of 22 males CFS and 18 age- and sex-matched controls.

    RESULTS:
    Optimization of LC conditions and MS/MS parameters enabled the measurement of 610 key metabolites from 63 biochemical pathways and 95 stable isotope standards in a 45-minute HILIC method using a single injection without sacrificing sensitivity. The total imprecision (CVtotal) of peak area was 12% for both the control and CFS pools. The 8 metabolites selected in our previous study (PMID: 27573827) performed well in a clinical validation analysis even when the case and control samples were analyzed 1.5 years later on a different instrument by a different investigator, yielding a diagnostic accuracy of 95% (95% CI 85-100%) measured by the area under the ROC curve.

    CONCLUSIONS:
    A reliable and reproducible, broad-spectrum, targeted metabolomic method was developed, capable of measuring over 600 metabolites in plasma in a single injection. The method might be a useful tool in helping the diagnosis of CFS or other complex diseases.

    KEYWORDS:
    Broad-spectrum; Chronic fatigue syndrome; Hydrophilic interaction chromatography; LC-MS/MS; Targeted metabolomics; Validation

    https://www.ncbi.nlm.nih.gov/pubmed/28943831
    https://link.springer.com/article/10.1007/s11306-017-1264-1
     
    merylg, Valentijn, ballard and 2 others like this.
  2. greeneagledown

    greeneagledown Senior Member

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    Can someone scientifically inclined tell me what it means for the total imprecision of peak area to be 12%? I have no idea what it means but it sounds like a lot of imprecision!
     
    ivorin likes this.
  3. ivorin

    ivorin Senior Member

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    Sounds like we have a metabolic footprint reading technique that could economically identify specific metabolic profiles like that of cfs. Am I reading this correctly?
     
  4. RogerBlack

    RogerBlack Senior Member

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    http://www.ebay.com/itm/AB-Sciex-45...stem-with-Computer-and-Warranty-/112572375921 - as some context - this is a used though in warranty system, but last years model, for $170K.

    So, not exactly cheap. I would be rather surprised if you could setup a suitable lab with a machine of this class for $500K, neglecting any clinical approvals that may be required.

    I do wish I had a spare $1M, a serial metabolic survey with 3 hourly time-points and correlations would be fascinating.

    If I am reading the paper correctly, the above machine can process about a sample an hour. So, even going flat out, would only do 10000 tests a year. (and it needs multiple costly changes of consumables to do that)
     
    Last edited: Sep 26, 2017
    ivorin likes this.
  5. ivorin

    ivorin Senior Member

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    Still, having a prime position to potentially diagnose (or at least provide solid probability) of cfs for the millions looking for a marker makes the investment a reasonably intelligent move for larger labs. I'm hoping to see this available soon.
     
    ballard and merylg like this.

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