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Record W4413257644 · doi:10.1021/acs.analchem.5c02047

Reverse Spectral Search Reimagined: A Simple but Overlooked Solution for Chimeric Spectral Annotation

2025· article· en· W4413257644 on OpenAlexfundno aff
Shipei Xing, Vincent Charron‐Lamoureux, Haoqi Nina Zhao, Yasin El Abiead, Mingxun Wang, Pieter C. Dorrestein

Bibliographic record

VenueAnalytical Chemistry · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMetabolomics and Mass Spectrometry Studies
Canadian institutionsnot available
FundersBiotechnology and Biological Sciences Research CouncilUniversity of California, RiversideChan Zuckerberg InitiativeFonds de Recherche du Québec - SantéNational Institute of Health Sciences
KeywordsChemistryBottleneckFragmentation (computing)AlgorithmComputer scienceOperating system

Abstract

fetched live from OpenAlex

The exponential growth of untargeted metabolomics data, now reaching billions of mass spectra in public repositories, benefits from reannotation strategies for data reuse. While tandem mass spectrometry (MS/MS) library matching remains the gold standard, annotation workflows face a critical bottleneck: chimeric spectra. These composite spectra, arising from simultaneous fragmentation of multiple precursor ions, compromise the ability to annotate MS/MS spectra against nonchimeric reference spectra. Here, we demonstrate that an enhanced version of reverse spectral search, a principle first introduced in 1975 but largely overlooked, provides a simple, computationally efficient solution, rescuing up to 62% more metabolite annotations in benchmark data sets while maintaining stringent quality control. The enhanced reverse spectral search is now added to the GNPS ecosystem. Source codes can be accessed at https://github.com/Philipbear/reverse_search.

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)0.007
metaresearch head score (Gemma)0.020
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.010
Threshold uncertainty score0.036

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0070.020
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0020.003
Bibliometrics0.0020.003
Science and technology studies0.0020.002
Scholarly communication0.0040.006
Open science0.0040.008
Research integrity0.0030.004
Insufficient payload (model declined to judge)0.0100.010

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 head0.013
GPT teacher head0.291
Teacher spread0.278 · 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.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreMethods

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

Citations5
Published2025
Admission routes1
Has abstractyes

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