rewirebio.iobenchmarks
Contested result

MutScore and ESM-1b: Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML) and An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers disagree

  • Low severity
  • Not yet reviewed
  • two-study-conflict
  • unknown

Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML) ranks ESM-1b above MutScore in 6 of 7 comparisons; An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers ranks MutScore above ESM-1b in 6 of 6 comparisons. No other study gives a verdict, so neither is the outlier.

An automatic lead, not a finding of error. The results below are shown as published, everywhere on the site, until a reviewer decides otherwise.

Which studies agree

2 papers rank MutScore above ESM-1b in 7 of their 13 comparisons and ESM-1b higher in 6. Of those papers, Livesey and Marsh 2025 ranks ESM-1b higher on its own (6 of 7).

Papers grouped by which system they rank higher: MutScore or ESM-1bRank MutScore higher: An openly licensed benchmark…. Rank ESM-1b higher: Livesey and Marsh 2025. Mixed: none.Rank MutScore higherMixedRank ESM-1b higherAn openly licensedbenchmark…An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer driversLivesey and Marsh 2025Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)
  • Rank MutScore higher (1): An openly licensed benchmark…
  • Rank ESM-1b higher (1): Livesey and Marsh 2025
  • Mixed (0): none

Each paper sits where at least two thirds of its comparisons point; Mixed means neither model reaches two thirds. The larger, outlined dot is the paper that disagrees.

Comparisons in which each paper scores MutScore or ESM-1b higherLivesey and Marsh 2025: MutScore higher in 1, ESM-1b higher in 6, 0 ties. An openly licensed benchmark…: MutScore higher in 6, ESM-1b higher in 0, 0 ties.Livesey and Marsh 2025Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)1 MutScore higher16 ESM-1b higher6An openly licensed benchmark…An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers6 MutScore higher6
MutScore higherTieESM-1b higherNumbers are counts of comparisons; the outlined bar is the paper that disagrees.
Comparisons in Livesey and Marsh 2025 (7)
ProtocolDatasetMetricMutScoreESM-1bHigher
Livesey and Marsh 2025 clinical benchmark: pairwise AUROC win rate, ClinVar pathogenic versus gnomAD missenseLivesey and Marsh 2025 clinical set: ClinVar pathogenic versus gnomAD v4.1 missense (819 proteins)Pairwise win rate (average pairwise win rate against all other VEPs, per-protein AUROC on shared variants, ClinVar P/LP versus gnomAD v4.1 missense, proteins with at least 10 of each), percent76.654.3MutScore
Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, all 36 DMS setsLivesey and Marsh 2025 human DMS benchmark set (36 proteins)Pairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, 36 human DMS sets), percent63.465ESM-1b
Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, all 36 DMS setsLivesey and Marsh 2025 human DMS benchmark set (36 proteins)Pairwise win rate (average pairwise win rate against the five top-ranked VEPs (column top_5_winrate; the five are not listed in the table), |Spearman| with DMS on shared variants, 36 human DMS sets), percent8.6414.7ESM-1b
Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, direct assays onlyLivesey and Marsh 2025 human DMS benchmark set (36 proteins)Pairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, direct DMS assays only), percent61.562.4ESM-1b
Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, indirect assays onlyLivesey and Marsh 2025 human DMS benchmark set (36 proteins)Pairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, indirect DMS assays only), percent64.867ESM-1b
Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions onlyLivesey and Marsh 2025 human DMS benchmark set (36 proteins)Pairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, SNV-accessible substitutions only), percent63.464.5ESM-1b
Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions with gaps filledLivesey and Marsh 2025 human DMS benchmark set (36 proteins)Pairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS, SNV-accessible substitutions, missing predictions filled with the VEP's most benign score), percent63.265.9ESM-1b
Comparisons in An openly licensed benchmark… (6)
ProtocolDatasetMetricMutScoreESM-1bHigher
CGC missense oncogenicity, all genes (Lee 2026, OncoCal tool_performance.tsv)Missense variants in 768 Cancer Gene Census genes with open oncogenicity labelsAUROC (CGC missense, all genes), unitless0.8760.842MutScore
CGC missense oncogenicity, all genes (Lee 2026, OncoCal tool_performance.tsv)Missense variants in 768 Cancer Gene Census genes with open oncogenicity labelsAverage precision (CGC missense, all genes), unitless0.7540.641MutScore
CGC missense oncogenicity, oncogenes (gain of function) (Lee 2026, OncoCal tool_performance.tsv)Missense variants in 768 Cancer Gene Census genes with open oncogenicity labelsAUROC (CGC missense, oncogenes (gain of function)), unitless0.8770.841MutScore
CGC missense oncogenicity, oncogenes (gain of function) (Lee 2026, OncoCal tool_performance.tsv)Missense variants in 768 Cancer Gene Census genes with open oncogenicity labelsAverage precision (CGC missense, oncogenes (gain of function)), unitless0.8090.719MutScore
CGC missense oncogenicity, tumour suppressors (loss of function) (Lee 2026, OncoCal tool_performance.tsv)Missense variants in 768 Cancer Gene Census genes with open oncogenicity labelsAUROC (CGC missense, tumour suppressors (loss of function)), unitless0.8980.858MutScore
CGC missense oncogenicity, tumour suppressors (loss of function) (Lee 2026, OncoCal tool_performance.tsv)Missense variants in 768 Cancer Gene Census genes with open oncogenicity labelsAverage precision (CGC missense, tumour suppressors (loss of function)), unitless0.720.594MutScore

What disagrees

studies
2
Compared
MutScore, ESM-1b
Study that disagrees
Other studies
Rule
two-study-conflict; unknown
Model identity
Matched across studies partly through links not yet reviewed

Follow-up

Current state: Not yet reviewed.

No one has reviewed this finding yet.

How to help resolve this

If you know why these studies disagree, for example a different population, metric or preprocessing step, or you have a corrected value, tell us through the contribution form. A reviewer checks every submission against its source before anything changes, and the step is added to the follow-up above.

Finding discrepancy-dcdce8c162cc0827 · All contested results · How findings are made and followed up