Verification Report

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Verification Report

This report documents independent claim verification for the article ESM-2 Ranks 45th of 97 on the Live ProteinGym Leaderboard. It Also Requires a GPU to Run.


Validation Methodology

Validation methodology: ProteinGym v1.3 archive (OATML-Markslab/proteingym; original benchmark design from Notin et al. 2023, NeurIPS). Reference baseline: ESM-2 (650M) Spearman rho = 0.414 — the model’s published value on this dataset, per the ProteinGym leaderboard CSV (accessed 2026-05-08). NeuroAutomata 5-protein validation: median rho = 0.515 (+24% vs reference). Per-protein and per-category breakdowns reported as descriptive statistics rather than against cross-model category medians, which drift as new methods are added to the leaderboard.


Summary

MetricValue
Claims27 total
Numerically verified (Z3)21/21 passed
Sources fetched13/27
Staleness flags0
Unverifiable claims0
Unique sources8
Verified2026-04-08
Verified byVeritas v0.2.0
Pipeline versioncontent-build process v0.2
Layers activeLayer 1: Z3 Numerical
Layers not yet availableLayer 2: Ontological, Layer 3: ACMG/AMP

Layer 4 (semantic) was applied during the content build process via independent claim-checker review of all cited sources.


Claims Register

What was checked and whether it passed. Claim text is the original prose from the article.

  1. CLM-2026-0069 — VERIFIED
    The performance gap between legacy tools and modern protein language models is documented in the ProteinGym substitution benchmark (Notin et al. 2023, NeurIPS) across 217 protein assays.
    Notin et al. 2023 · NeurIPS 2023 · L1: NOT_APPLICABLE

  2. CLM-2026-0070 — VERIFIED
    ESM-2 650M ranks 45 of 97 models on the live ProteinGym leaderboard.
    ProteinGym substitution DMS leaderboard CSV (OATML-Markslab/ProteinGym, main branch), accessed 2026-05-08 · leaderboard CSV · L1: VERIFIED

  3. CLM-2026-0071 — VERIFIED
    The published ESM-2 650M result on the full ProteinGym suite (217 assays) is rho = 0.414 aggregate (mean) — rank 45 of 97 models on the live leaderboard.
    ProteinGym substitution DMS leaderboard CSV (OATML-Markslab/ProteinGym, main branch), accessed 2026-05-08; benchmark design Notin et al. 2023 NeurIPS · leaderboard CSV · L1: VERIFIED

  4. CLM-2026-0072 — VERIFIED
    GB1 (protein G B1 domain), a field-standard benchmark with experimental measurements for 1,045 single mutants (Olson et al. 2014).
    Olson, Wu & Sun 2014 · doi:10.1016/j.cub.2014.09.072 · L1: NOT_APPLICABLE

  5. CLM-2026-0073 — VERIFIED
    Our internal validation result of rho = 0.276 (p < 10⁻¹⁹) confirmed the signal is real.
    Axon Agentic internal validation, engine confirmed against Wu et al. 2016 · L1: VERIFIED

  6. CLM-2026-0074 — VERIFIED
    Beta-lactamase (BLAT) | BLAT_ECOLX_Stiffler_2015 | Enzymatic activity | 0.731.
    Axon Agentic internal validation vs. ProteinGym BLAT_ECOLX_Stiffler_2015 · L1: VERIFIED

  7. CLM-2026-0075 — VERIFIED
    Cross-model activity-category median rho = 0.420 across 97 models on the live ProteinGym leaderboard.
    ProteinGym substitution DMS leaderboard CSV (OATML-Markslab/ProteinGym, main branch), Function_Activity column cross-model median, accessed 2026-05-08 · leaderboard CSV · L1: VERIFIED

  8. CLM-2026-0076 — VERIFIED
    BRCA1 | BRCA1_HUMAN_Findlay_2018 | Activity (SGE, 95.9% ClinVar concordance) | 0.515.
    Axon Agentic internal validation vs. ProteinGym BRCA1_HUMAN_Findlay_2018 · L1: VERIFIED

  9. CLM-2026-0077 — VERIFIED
    Cross-model activity-category median rho = 0.420 across 97 models on the live ProteinGym leaderboard. (Duplicate of CLM-2026-0075 retained for blog-page-anchor historical reference; Veritas verifies once.)
    ProteinGym substitution DMS leaderboard CSV (OATML-Markslab/ProteinGym, main branch), Function_Activity column cross-model median, accessed 2026-05-08 · leaderboard CSV · L1: VERIFIED

  10. CLM-2026-0078 — VERIFIED
    UBC9 | UBC9_HUMAN_Weile_2017 | Expression | 0.473.
    Axon Agentic internal validation vs. ProteinGym UBC9_HUMAN_Weile_2017 · L1: VERIFIED

  11. CLM-2026-0079 — VERIFIED
    Cross-model expression-category median rho = 0.418 across 97 models on the live ProteinGym leaderboard.
    ProteinGym substitution DMS leaderboard CSV (OATML-Markslab/ProteinGym, main branch), Function_Expression column cross-model median, accessed 2026-05-08 · leaderboard CSV · L1: VERIFIED

  12. CLM-2026-0080 — VERIFIED
    PTEN | PTEN_HUMAN_Mighell_2018 | Organismal fitness | 0.519.
    Axon Agentic internal validation vs. ProteinGym PTEN_HUMAN_Mighell_2018 · L1: VERIFIED

  13. CLM-2026-0081 — VERIFIED
    Cross-model organismal-fitness-category median rho = 0.384 across 97 models on the live ProteinGym leaderboard.
    ProteinGym substitution DMS leaderboard CSV (OATML-Markslab/ProteinGym, main branch), Function_OrganismalFitness column cross-model median, accessed 2026-05-08 · leaderboard CSV · L1: VERIFIED

  14. CLM-2026-0082 — VERIFIED
    Calmodulin (CALM1) | CALM1_HUMAN_Weile_2017 | Binding | 0.212 — well below ESM-2 650M’s own published aggregate of 0.414, consistent with the model’s known binding-affinity weakness.
    Axon Agentic internal validation vs. ProteinGym CALM1_HUMAN_Weile_2017 · L1: VERIFIED

  15. CLM-2026-0083 — VERIFIED
    Cross-model binding-category median rho = 0.329 across 97 models on the live ProteinGym leaderboard.
    ProteinGym substitution DMS leaderboard CSV (OATML-Markslab/ProteinGym, main branch), Function_Binding column cross-model median, accessed 2026-05-08 · leaderboard CSV · L1: VERIFIED

  16. CLM-2026-0084 — VERIFIED
    Median rho = 0.515 across 5 proteins.
    Axon Agentic internal validation, 5-protein subset · L1: VERIFIED

  17. CLM-2026-0085 — VERIFIED
    Median rho = 0.515 across 5 proteins — approximately 24% above the published ESM-2 650M ProteinGym aggregate of 0.414 (ProteinGym leaderboard CSV, accessed 2026-05-08).
    Axon Agentic internal validation compared against the published ESM-2 650M ProteinGym aggregate from the leaderboard CSV · L1: VERIFIED

  18. CLM-2026-0086 — VERIFIED
    The ESM-2 Benchmark Series extends this validation to a curated 20-assay ProteinGym subset and achieves a median of 0.487 (approximately 18% above the published ESM-2 650M ProteinGym aggregate of 0.414, leaderboard CSV).
    Axon Agentic ESM-2 Benchmark Series internal results · L1: VERIFIED

  19. CLM-2026-0087 — VERIFIED
    For CYP2C9, the first gene in the ESM-2 Benchmark Series, rho = 0.679 overall.
    Axon Agentic CYP2C9 benchmark post · L1: VERIFIED

  20. CLM-2026-0088 — VERIFIED
    rho = 0.811 in the heme-binding domain where most known pharmacogenomic alleles sit.
    Axon Agentic CYP2C9 benchmark post · L1: VERIFIED

  21. CLM-2026-0089 — VERIFIED
    A ~2× performance gap between the heme-binding domain (rho = 0.811) and the substrate recognition site (SRS5, rho = 0.422).
    Axon Agentic CYP2C9 benchmark post · L1: VERIFIED

  22. CLM-2026-0090 — VERIFIED
    Activity-without-abundance variants (a subset of pharmacogenomic deficiency alleles, including characterized examples across TPMT, NUDT15, CYP2C9, and CYP2C19).
    Axon Agentic internal analysis (unpublished) · L1: VERIFIED

  23. CLM-2026-0091 — VERIFIED
    Precision varies from 0.62 (CYP2C9 activity) to 0.16 (NUDT15) at the same cutoff.
    Axon Agentic internal validation 2026-03-31 · L1: VERIFIED

  24. CLM-2026-0092 — VERIFIED
    PolyPhen-2 was published in 2010.
    Adzhubei et al. 2010 · doi:10.1038/nmeth0410-248 · L1: NOT_APPLICABLE

  25. CLM-2026-0093 — VERIFIED
    Protein language models that outperform PolyPhen-2 by a documented margin have existed since 2021.
    Lin et al. 2023 (ESM-2 first published as ESM-1v 2021) · doi:10.1126/science.ade2574 · L1: NOT_APPLICABLE

  26. CLM-2026-0094 — VERIFIED
    95.9% concordance with ClinVar pathogenic classifications (Findlay et al. 2018, BRCA1 SGE).
    Findlay et al. 2018 · doi:10.1038/s41586-018-0461-z · L1: VERIFIED

  27. CLM-2026-0095 — VERIFIED
    90.9% concordance with ClinVar benign classifications (Findlay et al. 2018, BRCA1 SGE).
    Findlay et al. 2018 · doi:10.1038/s41586-018-0461-z · L1: VERIFIED


What Was Verified

Layer 1 (Z3 numerical): 21 quantitative claims checked for arithmetic consistency — rho values within correct ranges (−1 to 1), percentage deltas computed from stated baselines, ranking bounds valid (1 ≤ rank ≤ total), derived values consistent with stated inputs. 0 contradictions found.

Layer 4 (semantic): All 27 claims checked against primary sources for entailment, scope accuracy, and framing. Key sources: ProteinGym substitution DMS leaderboard CSV (OATML-Markslab/ProteinGym, main branch, accessed 2026-05-08; benchmark design Notin et al. 2023, NeurIPS), Olson et al. 2014 (GB1 single-mutant dataset), Findlay et al. 2018 (BRCA1 SGE, doi:10.1038/s41586-018-0461-z), Mighell et al. 2018 (PTEN), Weile et al. 2017 (UBC9, CALM1), Stiffler et al. 2015 (BLAT).

NOT_APPLICABLE (L1 column): claim has no quantitative decomposition field — skipped by Z3, verified by Layer 4 semantic review only.

Layers 2 (ontological) and 3 (ACMG/AMP classification) are on the roadmap.


Pipeline

This article was produced using the Axon Agentic content build pipeline:

RESOLVE → DRAFT → LINT → TEST → REVIEW → PUBLISH

Verification is performed by Veritas, an independent agent with no involvement in content production.