Evidence map›Paper›PMID 34321638›Full record

ArticleNature protocols2021

Statistical analysis in metabolic phenotyping.

Benjamin J Blaise, Gonçalo D S Correia, Gordon A Haggart, Izabella Surowiec, Caroline Sands, Matthew R Lewis, Jake T M Pearce, Johan Trygg, Jeremy K Nicholson, Elaine Holmes and 1 more

Abstract readEvaluation Study
PubMed Publisher
In one paragraph

Article in Nature protocols, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
–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

47 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Metabolite Fraction Libraries for Quantitative NMR Metabolomics.bioRxiv : the preprint server for biology · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. NMR-Based Stable Isotope Tracing of Cancer Metabolism.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  13. Review
  14. Article
  15. Article
  16. Observational
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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

11 authors.

Benjamin J Blaise *Division of Systems Medicine, Department of Metabolism, Digestion & Reproduction, Faculty of Medicine, Imperial College London, London, UK.
Gonçalo D S Correia *Division of Systems Medicine, Department of Metabolism, Digestion & Reproduction, Faculty of Medicine, Imperial College London, London, UK.
Gordon A Haggart *Division of Systems Medicine, Department of Metabolism, Digestion & Reproduction, Faculty of Medicine, Imperial College London, London, UK.ORCID 0000-0002-7538-151X
Izabella SurowiecComputational Life Science Cluster, Department of Chemistry, Umeå University, Umeå, Sweden.
Caroline SandsDivision of Systems Medicine, Department of Metabolism, Digestion & Reproduction, Faculty of Medicine, Imperial College London, London, UK.
Matthew R LewisDivision of Systems Medicine, Department of Metabolism, Digestion & Reproduction, Faculty of Medicine, Imperial College London, London, UK.
Jake T M PearceDivision of Systems Medicine, Department of Metabolism, Digestion & Reproduction, Faculty of Medicine, Imperial College London, London, UK.ORCID 0000-0003-4637-3171
Johan TryggComputational Life Science Cluster, Department of Chemistry, Umeå University, Umeå, Sweden.
Jeremy K NicholsonAustralian National Phenome Centre, Health Futures Institute, Murdoch University, Perth, Western Australia, Australia.ORCID 0000-0002-8123-8349
Elaine HolmesDivision of Systems Medicine, Department of Metabolism, Digestion & Reproduction, Faculty of Medicine, Imperial College London, London, UK.ORCID 0000-0002-0556-8389
Timothy M D EbbelsDivision of Systems Medicine, Department of Metabolism, Digestion & Reproduction, Faculty of Medicine, Imperial College London, London, UK. t.ebbels@imperial.ac.uk.ORCID 0000-0002-3372-8423

Funding

Metabolomic Signatures of CAD Associated GenotypesR01HL133932 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI BOWDEN, DONALD W, HERRINGTON, DAVID MCLEOD · 2016 to 2019
$2.5M
Biotechnology and Biological Sciences Research Council BB/T007974/1Medical Research Council MC_PC_12025Medical Research Council MR/S010483/1Medical Research Council MR/S019669/1NHLBI NIH HHS R01 HL133932
6 · The paper itself

Abstract

Metabolic phenotyping is an important tool in translational biomedical research. The advanced analytical technologies commonly used for phenotyping, including mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy, generate complex data requiring tailored statistical analysis methods. Detailed protocols have been published for data acquisition by liquid NMR, solid-state NMR, ultra-performance liquid chromatography (LC-)MS and gas chromatography (GC-)MS on biofluids or tissues and their preprocessing. Here we propose an efficient protocol (guidelines and software) for statistical analysis of metabolic data generated by these methods. Code for all steps is provided, and no prior coding skill is necessary. We offer efficient solutions for the different steps required within the complete phenotyping data analytics workflow: scaling, normalization, outlier detection, multivariate analysis to explore and model study-related effects, selection of candidate biomarkers, validation, multiple testing correction and performance evaluation of statistical models. We also provide a statistical power calculation algorithm and safeguards to ensure robust and meaningful experimental designs that deliver reliable results. We exemplify the protocol with a two-group classification study and data from an epidemiological cohort; however, the protocol can be easily modified to cover a wider range of experimental designs or incorporate different modeling approaches. This protocol describes a minimal set of analyses needed to rigorously investigate typical datasets encountered in metabolic phenotyping.

Indexed as

Genetic TechniquesPhenotypeSoftwareStatistics as TopicHumansMetabolismMetabolomics

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.