{
  "abstract": "Compound annotation in untargeted metabolomics relies on matching an experimental MS/MS spectrum against a reference library, and the quality of such libraries is routinely summarized by the proportion of spectrum pairs exceeding a similarity threshold. We show that this class of metric is structurally invalid. Analyzing 1,022,449 spectra covering 66,843 compounds from GNPS, MS-DIAL, and MassBank of North America, we compute all within- and between-compound pairwise similarities and demonstrate that proportion-based consistency estimates are confounded by sampling depth as a matter of construction: the apparent high-consistency rate falls from 91% for compound groups supported by a single comparison to 5% for groups supported by more than one hundred. Consequently, any comparison of libraries, instrument platforms, or acquisition conditions that does not control depth measures coverage rather than quality — an apparent advantage of one instrument platform over another narrows substantially once depth is matched. We further identify a resolution floor that no improvement in library curation can remove: 31.7% of compounds share near-identical spectra (cosine ≥ 0.9) with at least one structurally distinct compound, so for these the identification is underdetermined by spectral matching alone. Against this corrected framework, 49.6% of 12,613,259 same-compound comparisons fall below the conventional 0.7 threshold and 6.4% of spectra behave as outliers within their own compound group. We release the collection annotated with spectrum-, group-, and compound-level metrics, each reported alongside the evidence supporting it rather than as a bare proportion, together with the pipeline as an open-source R package.",
  "abstract_shown": true,
  "affiliations": [
    "Independent Researcher"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yongseok Kim",
      "orcid": "0000-0001-7861-7375"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/163pqkch7jmhc.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15008195/v1",
  "fulltext_url": null,
  "id": "163pqkch7jmhc",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008195/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Metabolomics and Mass Spectrometry Studies"
    ]
  ],
  "openalex": "W7204993907",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15008195/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-02",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/163pqkch7jmhc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.26434/chemrxiv.15008195",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008195/v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Metabolomics and Mass Spectrometry Studies",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Reproducibility Limits of Public MS/MS Spectral Libraries: Irreproducibility, Outlier Spectra, and Indistinguishable Compounds Across One Million Reference Spectra",
  "title_text": "Reproducibility Limits of Public MS/MS Spectral Libraries: Irreproducibility, Outlier Spectra, and Indistinguishable Compounds Across One Million Reference Spectra",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:17Z",
  "url": "https://research.draconitic.com/paper/163pqkch7jmhc",
  "venue": "ChemRxiv",
  "versions": []
}