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Record W4412572177 · doi:10.1021/acs.analchem.4c05577

Multilaboratory Untargeted Mass Spectrometry Metabolomics Collaboration to Identify Bottlenecks and Comprehensively Annotate A Single Dataset

2025· article· en· W4412572177 on OpenAlexaff
Joëlle Houriet, Preston K. Manwill, Armando Alcázar Magaña, Victoria M. Anderson, Mehdi A. Beniddir, Samuel Bertrand, Jaewoo Choi, Trevor N. Clark, Leonard J. Foster, Maria Halabalaki, Alan K. Jarmusch, Niek De Jonge, Aswad Khadilkar, John B. MacMillan, Claudia S. Maier, Luke Marney, Guillaume Marti, Eleni V. Mikropoulou, Damien Olivier‐Jimenez, Amélie Perez, Justin J. J. van der Hooft, Mitja M. Zdouc, Roger G. Linington, Nadja B. Cech

Bibliographic record

VenueAnalytical Chemistry · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMetabolomics and Mass Spectrometry Studies
Canadian institutionsSimon Fraser UniversityUniversity of British Columbia
FundersH2020 FoodNational Center for Complementary and Integrative HealthNational Institutes of HealthOffice of Dietary SupplementsAgence Nationale de la RechercheNational Institute of Environmental Health SciencesEuropean Commission
KeywordsChemistryMetabolomicsMass spectrometryComputational biologyChromatography

Abstract

fetched live from OpenAlex

High Resolution Image Download MS PowerPoint Slide Annotation is the process of assigning features in mass spectrometry metabolomics data sets to putative chemical structures or “analytes.” The purpose of this study was to identify challenges in the annotation of untargeted mass spectrometry metabolomics datasets and suggest strategies to overcome them. Toward this goal, we analyzed an extract of the plant ashwagandha ( Withania somnifera ) using liquid chromatography–mass spectrometry on two different platforms (an Orbitrap and Q-ToF) with various acquisition modes. The resulting 12 datasets were shared with ten teams that had established expertise in metabolomics data interpretation. Each team annotated at least one positive ion dataset using their own approaches. Eight teams selected the positive ion mode data-dependent acquisition (DDA) data collected on the Orbitrap platform, so the results reported for that dataset were chosen for an in-depth comparison. We compiled and cross-checked the annotations of this dataset from each laboratory to arrive at a “consensus annotation,” which included 142 putative analytes, of which 13 were confirmed by comparison with standards. Each team only reported a subset (24 to 57%) of the analytes in the consensus list. Correct assignment of ion species (clusters and fragments) in MS spectra was a major bottleneck. In many cases, in-source redundant features were mistakenly considered to be independent analytes, causing annotation errors and resulting in overestimation of sample complexity. Our results suggest that better tools/approaches are needed to effectively assign feature identity, group related mass features, and query published spectral and taxonomic data when assigning putative analyte structures.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.053
metaresearch head score (Gemma)0.048
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesnone
DomainCandidate signal: Reproducibility · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.947
Threshold uncertainty score0.282

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0530.048
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0060.005
Science and technology studies0.0040.002
Scholarly communication0.0070.007
Open science0.0050.020
Research integrity0.0030.004
Insufficient payload (model declined to judge)0.0030.005

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.012
GPT teacher head0.304
Teacher spread0.292 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

Study designObservational
DomainReproducibility
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations7
Published2025
Admission routes1
Has abstractyes

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