Evidence map›Paper›PMID 37537184›Full record

ArticleNature communications2023

Simultaneously discovering the fate and biochemical effects of pharmaceuticals through untargeted metabolomics.

Tara J Bowen, Andrew D Southam, Andrew R Hall, Ralf J M Weber, Gavin R Lloyd, Ruth Macdonald, Amanda Wilson, Amy Pointon, Mark R Viant

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
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

14 citing papers in PubMed, 26 citations in OpenAlex.

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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

9 authors at 2 institutions in 1 country.

Tara J BowenSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.ORCID 0000-0001-7365-5372
Andrew D SouthamSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.ORCID 0000-0003-3030-7663
Andrew R HallSafety Sciences, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Ralf J M WeberSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.ORCID 0000-0002-8796-4771
Gavin R LloydPhenome Centre Birmingham, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.ORCID 0000-0001-7989-6695
Ruth MacdonaldAnimal Sciences and Technology, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Amanda WilsonIntegrated Bioanalysis, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0002-2659-1799
Amy PointonSafety Sciences, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0001-9716-9811
Mark R ViantSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. m.viant@bham.ac.uk.ORCID 0000-0001-5898-4119
University of Birmingham · GBAstraZeneca (United Kingdom) · GB

Funding

Biotechnology and Biological Sciences Research Council BB/S507064/1
6 · The paper itself

Abstract

Untargeted metabolomics is an established approach in toxicology for characterising endogenous metabolic responses to xenobiotic exposure. Detecting the xenobiotic and its biotransformation products as part of the metabolomics analysis provides an opportunity to simultaneously gain deep insights into its fate and metabolism, and to associate the internal relative dose directly with endogenous metabolic responses. This integration of untargeted exposure and response measurements into a single assay has yet to be fully demonstrated. Here we assemble a workflow to discover and analyse pharmaceutical-related measurements from routine untargeted UHPLC-MS metabolomics datasets, derived from in vivo (rat plasma and cardiac tissue, and human plasma) and in vitro (human cardiomyocytes) studies that were principally designed to investigate endogenous metabolic responses to drug exposure. Our findings clearly demonstrate how untargeted metabolomics can discover extensive biotransformation maps, temporally-changing relative systemic exposure, and direct associations of endogenous biochemical responses to the internal dose.

Indexed as

MetabolomicsXenobioticsAnimalsBiotransformationHumansMetabolomeRatsXenobiotics

Identifiers

PMID37537184
PMCPMC10400635
OpenAlexW4385551607

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.