rewirebio.iobenchmarks
Contested result

GenoCanyon and phyloP: Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods reverses the order

  • Low severity
  • Not yet reviewed
  • Ordering reversal
  • Same task, different protocols

Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods ranks GenoCanyon above phyloP in 3 of 3 comparisons; 2 of 2 other studies rank phyloP above GenoCanyon.

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 phyloP above GenoCanyon in 11 of their 13 comparisons and GenoCanyon higher in 1; 1 is a tie. Brandes et al. 2023 ranks GenoCanyon above phyloP in all 3 comparisons that are not ties (1 is a tie).

Papers grouped by which system they rank higher: phyloP or GenoCanyonRank phyloP higher: Livesey and Marsh 2025, Clinical likelihood ratios and balanced…. Rank GenoCanyon higher: Brandes et al. 2023 (disagrees). Mixed: none.Rank phyloP higherMixedRank GenoCanyon higherLivesey and Marsh 2025Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)Clinical likelihoodratios and balanced…Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genesBrandes et al. 2023Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods
  • Rank phyloP higher (2): Livesey and Marsh 2025, Clinical likelihood ratios and balanced…
  • Rank GenoCanyon higher (1): Brandes et al. 2023 (disagrees)
  • 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 phyloP or GenoCanyon higherBrandes et al. 2023 (disagrees): phyloP higher in 0, GenoCanyon higher in 3, 1 tie. Livesey and Marsh 2025: phyloP higher in 6, GenoCanyon higher in 1, 0 ties. Clinical likelihood ratios and balanced…: phyloP higher in 5, GenoCanyon higher in 0, 1 tie.Disagrees: Brandes et al. 2023Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods1 tie13 GenoCanyon higher3Livesey and Marsh 2025Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)6 phyloP higher61 GenoCanyon higher1Clinical likelihood ratios and balanced…Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes5 phyloP higher51 tie1
phyloP higherTieGenoCanyon higherNumbers are counts of comparisons; the outlined bar is the paper that disagrees.
Comparisons in Brandes et al. 2023 (4)
Comparisons in Livesey and Marsh 2025 (7)
ProtocolDatasetMetricphyloPGenoCanyonHigher
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), percent23.414.3phyloP
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), percent15.49.05phyloP
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), percent0.6671.22GenoCanyon
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), percent17.78.65phyloP
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), percent13.89.35phyloP
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), percent15.49.05phyloP
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), percent16.79.87phyloP
Comparisons in Clinical likelihood ratios and balanced… (6)
ProtocolDatasetMetricphyloPGenoCanyonHigher
BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)BRCA1 functional truth set: 1641 missense variants classed deleterious or tolerated by HAP1 cell survival after saturation genome editingBenignity likelihood ratio (Source 'negative likelihood ratio' (TNR/FNR): likelihood ratio for benignity of a tolerated call, BRCA1 functional truth set), unitless4.121.26phyloP
BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)BRCA1 functional truth set: 1641 missense variants classed deleterious or tolerated by HAP1 cell survival after saturation genome editingFalse negatives (Functionally deleterious BRCA1 variants called tolerated), count46231phyloP
BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)BRCA1 functional truth set: 1641 missense variants classed deleterious or tolerated by HAP1 cell survival after saturation genome editingLikelihood ratio (Positive likelihood ratio of a deleterious call (TPR/FPR), BRCA1 functional truth set), unitless1.791.78Tie
BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)BRCA2 functional truth set: 188 missense variants classed deleterious or tolerated by Homology-directed repairBenignity likelihood ratio (Source 'negative likelihood ratio' (TNR/FNR): likelihood ratio for benignity of a tolerated call, BRCA2 functional truth set), unitless16.16.24phyloP
BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)BRCA2 functional truth set: 188 missense variants classed deleterious or tolerated by Homology-directed repairFalse negatives (Functionally deleterious BRCA2 variants called tolerated), count12phyloP
BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)BRCA2 functional truth set: 188 missense variants classed deleterious or tolerated by Homology-directed repairLikelihood ratio (Positive likelihood ratio of a deleterious call (TPR/FPR), BRCA2 functional truth set), unitless1.311.2phyloP

What disagrees

Other studies
rank phyloP above GenoCanyon in 11 of 12 comparisons
This study
ranks GenoCanyon above phyloP in 3 of 3 comparisons
Compared
GenoCanyon, phyloP
Study that disagrees
Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods
Other studies
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes, Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx), Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML), Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8)
Rule
Ordering reversal; same task, different protocols
Model identity
Matched across studies partly through links not yet reviewed

The compared numbers

Each value links to its result record and source. Compare values within one protocol; the rule compares rankings, not raw values across protocols.

In the study that disagrees (6)
StudyToolProtocol or benchmarkMetricValue
Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods; Genome-wide prediction of disease variant effects with a deep protein language model (Brandes et al., Nature Genetics 2023)GenoCanyon (Brandes et al. 2023 clinical benchmarks)ClinVar missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2)AUPRC (balanced PRC-AUC: mean over 100 random downsamples to equal pathogenic and benign counts (80% of the minority class); zero-shot)0.682
Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods; Genome-wide prediction of disease variant effects with a deep protein language model (Brandes et al., Nature Genetics 2023)GenoCanyon (Brandes et al. 2023 clinical benchmarks)ClinVar missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2)AUROC (global ROC-AUC over all variants; zero-shot)0.685
Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods; Genome-wide prediction of disease variant effects with a deep protein language model (Brandes et al., Nature Genetics 2023)phyloP (mammalian) (Brandes et al. 2023 clinical benchmarks)ClinVar missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2)AUPRC (balanced PRC-AUC: mean over 100 random downsamples to equal pathogenic and benign counts (80% of the minority class); zero-shot)0.633
Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods; Genome-wide prediction of disease variant effects with a deep protein language model (Brandes et al., Nature Genetics 2023)phyloP (mammalian) (Brandes et al. 2023 clinical benchmarks)ClinVar missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2)AUROC (global ROC-AUC over all variants; zero-shot)0.671
Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods; Genome-wide prediction of disease variant effects with a deep protein language model (Brandes et al., Nature Genetics 2023)GenoCanyon (Brandes et al. 2023 clinical benchmarks)HGMD/gnomAD missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2)AUPRC (balanced PRC-AUC: mean over 100 random downsamples to equal pathogenic and benign counts (80% of the minority class); zero-shot)0.734
Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods; Genome-wide prediction of disease variant effects with a deep protein language model (Brandes et al., Nature Genetics 2023)phyloP (mammalian) (Brandes et al. 2023 clinical benchmarks)HGMD/gnomAD missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2)AUPRC (balanced PRC-AUC: mean over 100 random downsamples to equal pathogenic and benign counts (80% of the minority class); zero-shot)0.68
In the other studies (24)
StudyToolProtocol or benchmarkMetricValue
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)GenoCanyon (Cubuk et al. 2021)BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)Benignity likelihood ratio (Source 'negative likelihood ratio' (TNR/FNR): likelihood ratio for benignity of a tolerated call, BRCA1 functional truth set)1.26
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)GenoCanyon (Cubuk et al. 2021)BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)False negatives (Functionally deleterious BRCA1 variants called tolerated)231
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)GenoCanyon (Cubuk et al. 2021)BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)Benignity likelihood ratio (Source 'negative likelihood ratio' (TNR/FNR): likelihood ratio for benignity of a tolerated call, BRCA2 functional truth set)6.24
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)GenoCanyon (Cubuk et al. 2021)BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)False negatives (Functionally deleterious BRCA2 variants called tolerated)2
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)GenoCanyon (Cubuk et al. 2021)BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)Likelihood ratio (Positive likelihood ratio of a deleterious call (TPR/FPR), BRCA2 functional truth set)1.2
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)phyloP100way_vertebrate (Cubuk et al. 2021)BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)Benignity likelihood ratio (Source 'negative likelihood ratio' (TNR/FNR): likelihood ratio for benignity of a tolerated call, BRCA1 functional truth set)4.12
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)phyloP100way_vertebrate (Cubuk et al. 2021)BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021)False negatives (Functionally deleterious BRCA1 variants called tolerated)46
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)phyloP100way_vertebrate (Cubuk et al. 2021)BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)Benignity likelihood ratio (Source 'negative likelihood ratio' (TNR/FNR): likelihood ratio for benignity of a tolerated call, BRCA2 functional truth set)16.1
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)phyloP100way_vertebrate (Cubuk et al. 2021)BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)False negatives (Functionally deleterious BRCA2 variants called tolerated)1
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx)phyloP100way_vertebrate (Cubuk et al. 2021)BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021)Likelihood ratio (Positive likelihood ratio of a deleterious call (TPR/FPR), BRCA2 functional truth set)1.31
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)GenoCanyon (Livesey and Marsh 2025)Livesey and Marsh 2025 clinical benchmark: pairwise AUROC win rate, ClinVar pathogenic versus gnomAD missensePairwise 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)14.3
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)phyloP (Livesey and Marsh 2025)Livesey and Marsh 2025 clinical benchmark: pairwise AUROC win rate, ClinVar pathogenic versus gnomAD missensePairwise 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)23.4
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)GenoCanyon (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, all 36 DMS setsPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, 36 human DMS sets)9.05
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)GenoCanyon (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, all 36 DMS setsPairwise 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)1.22
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)phyloP (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, all 36 DMS setsPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, 36 human DMS sets)15.4
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)phyloP (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, all 36 DMS setsPairwise 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)0.667
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)GenoCanyon (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, direct assays onlyPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, direct DMS assays only)8.65
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)phyloP (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, direct assays onlyPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, direct DMS assays only)17.7
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)GenoCanyon (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, indirect assays onlyPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, indirect DMS assays only)9.35
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)phyloP (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, indirect assays onlyPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, indirect DMS assays only)13.8
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)GenoCanyon (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions with gaps filledPairwise 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)9.87
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)phyloP (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions with gaps filledPairwise 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)16.7
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)GenoCanyon (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions onlyPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, SNV-accessible substitutions only)9.05
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8); Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)phyloP (Livesey and Marsh 2025)Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions onlyPairwise win rate (average pairwise win rate against all other VEPs, |Spearman| with DMS on shared variants, SNV-accessible substitutions only)15.4

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-a79a672f2e6ae90f · All contested results · How findings are made and followed up