Evidence map›Paper›PMID 31548575›Full record

ArticleScientific reports2019

Integration of flux measurements and pharmacological controls to optimize stable isotope-resolved metabolomics workflows and interpretation.

Pawel K Lorkiewicz, Andrew A Gibb, Benjamin R Rood, Liqing He, Yuting Zheng, Brian F Clem, Xiang Zhang, Bradford G Hill

Abstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. American journal of physiology. Cell physiology · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Loss ofCancers · 2020
    Article
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Pawel K LorkiewiczDepartment of Medicine, Division of Environmental Medicine, Christina Lee Brown Envirome Institute, Diabetes and Obesity Center, University of Louisville, Louisville, USA.
Andrew A GibbDepartment of Medicine, Division of Environmental Medicine, Christina Lee Brown Envirome Institute, Diabetes and Obesity Center, University of Louisville, Louisville, USA.
Benjamin R RoodDepartment of Medicine, Division of Environmental Medicine, Christina Lee Brown Envirome Institute, Diabetes and Obesity Center, University of Louisville, Louisville, USA.
Liqing HeDepartment of Chemistry, Center for Regulatory and Environmental Analytical Metabolomics, University of Louisville, Louisville, USA.
Yuting ZhengDepartment of Medicine, Division of Environmental Medicine, Christina Lee Brown Envirome Institute, Diabetes and Obesity Center, University of Louisville, Louisville, USA.
Brian F ClemDepartment of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY, USA.
Xiang ZhangDepartment of Chemistry, Center for Regulatory and Environmental Analytical Metabolomics, University of Louisville, Louisville, USA.
Bradford G HillDepartment of Medicine, Division of Environmental Medicine, Christina Lee Brown Envirome Institute, Diabetes and Obesity Center, University of Louisville, Louisville, USA. bradford.hill@louisville.edu.

Funding

Role of oxidized linoleic acid metabolites in the pathogenesis of alcoholic liver diseaseP20GM113226 · NIGMS · UNIVERSITY OF LOUISVILLE · PI MCCLAIN, CRAIG J. · 2016 to 2025
$24.1M
The Role of Nutrition in the Development/Progression of Alcohol-Induced Organ InjuryP50AA024337 · NIAAA · UNIVERSITY OF LOUISVILLE · PI CRAIG J. MCCLAIN · 2016 to 2026
$17.9M
Biosynthetic Pathways in Cardiac RemodelingR01HL147844 · NHLBI · UNIVERSITY OF LOUISVILLE · PI HILL, BRADFORD GUY, JONES, STEVEN P · 2019 to 2022
$3.0M
Effects of Air Pollution on Stem Cell HealthR01ES028268 · NIEHS · UNIVERSITY OF LOUISVILLE · PI HABERZETTL, PETRA, HILL, BRADFORD GUY · 2018 to 2022
$2.2M
Metabolic optimization of cell therapyR01HL130174 · NHLBI · UNIVERSITY OF LOUISVILLE · PI HILL, BRADFORD GUY · 2016 to 2020
$1.9M
Ultra Performance Liquid Chromatography High Resolution High Mass Accuracy Mass SpectrometerS10OD020106 · OD · UNIVERSITY OF LOUISVILLE · PI ZHANG, XIANG · 2015 to 2015
$600k
American Heart Association-American Stroke Association 16PRE31010022NHLBI NIH HHS R01 HL130174NHLBI NIH HHS R01 HL147844NIAAA NIH HHS P50 AA024337NIEHS NIH HHS R01 ES028268NIGMS NIH HHS P20 GM113226NIH HHS S10 OD020106
6 · The paper itself

Abstract

Stable isotope-resolved metabolomics (SIRM) provides information regarding the relative activity of numerous metabolic pathways and the contribution of nutrients to specific metabolite pools; however, SIRM experiments can be difficult to execute, and data interpretation is challenging. Furthermore, standardization of analytical procedures and workflows remain significant obstacles for widespread reproducibility. Here, we demonstrate the workflow of a typical SIRM experiment and suggest experimental controls and measures of cross-validation that improve data interpretation. Inhibitors of glycolysis and oxidative phosphorylation as well as mitochondrial uncouplers serve as pharmacological controls, which help define metabolic flux configurations that occur under well-controlled metabolic states. We demonstrate how such controls and time course labeling experiments improve confidence in metabolite assignments as well as delineate metabolic pathway relationships. Moreover, we demonstrate how radiolabeled tracers and extracellular flux analyses integrate with SIRM to improve data interpretation. Collectively, these results show how integration of flux methodologies and use of pharmacological controls increase confidence in SIRM data and provide new biological insights.

Indexed as

WorkflowData Interpretation, StatisticalIsotope LabelingMass SpectrometryMetabolic Networks and PathwaysMetabolomicsReproducibility of Results

Identifiers

PMID31548575
PMCPMC6757038

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.