rewirebio.iobenchmarks
Contested result

DeepSequence and VESPA: ProteinGym: Large-Scale Benchmarks for Protein Fitness Prediction and Design and Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML) disagree

  • Low severity
  • Not yet reviewed
  • two-study-conflict
  • different-task

ProteinGym: Large-Scale Benchmarks for Protein Fitness Prediction and Design ranks VESPA above DeepSequence in 13 of 17 comparisons; Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML) ranks DeepSequence above VESPA in 5 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 DeepSequence above VESPA in 9 of their 26 comparisons and VESPA higher in 14; 3 are ties. Of those papers, ProteinGym ranks VESPA higher on its own (13 of 19).

Papers grouped by which system they rank higher: DeepSequence or VESPARank DeepSequence higher: Livesey and Marsh 2025. Rank VESPA higher: ProteinGym. Mixed: none.Rank DeepSequence higherMixedRank VESPA higherLivesey and Marsh 2025Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)ProteinGymProteinGym: Large-Scale Benchmarks for Protein Fitness Prediction and Design
  • Rank DeepSequence higher (1): Livesey and Marsh 2025
  • Rank VESPA higher (1): ProteinGym
  • 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 DeepSequence or VESPA higherProteinGym: DeepSequence higher in 4, VESPA higher in 13, 2 ties. Livesey and Marsh 2025: DeepSequence higher in 5, VESPA higher in 1, 1 tie.ProteinGymProteinGym: Large-Scale Benchmarks for Protein Fitness Prediction and Design4 DeepSequence higher42 tie213 VESPA higher13Livesey and Marsh 2025Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML)5 DeepSequence higher51 tie11 VESPA higher1
DeepSequence higherTieVESPA higherNumbers are counts of comparisons; the outlined bar is the paper that disagrees.
Papers compared (2)
PaperRoleRanks DeepSequence higherRanks VESPA higherTies
ProteinGym: Large-Scale Benchmarks for Protein Fitness Prediction and Design and 6 more records · DOIAgrees4132
Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML) and 1 more record · DOIAgrees511
Comparisons in ProteinGym (19)
ProtocolDatasetMetricDeepSequenceVESPAHigher
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, Activity assays: mean over proteins of assay-level Spearman), unitless0.4550.468VESPA
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, Binding assays: mean over proteins of assay-level Spearman), unitless0.3630.366Tie
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, Expression assays: mean over proteins of assay-level Spearman), unitless0.390.404VESPA
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, High MSA depth proteins: mean over proteins of assay-level Spearman), unitless0.4740.484VESPA
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, Human proteins: mean over proteins of assay-level Spearman), unitless0.4430.44Tie
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, Low MSA depth proteins: mean over proteins of assay-level Spearman), unitless0.370.42VESPA
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, Medium MSA depth proteins: mean over proteins of assay-level Spearman), unitless0.4310.455VESPA
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, Organismal fitness assays: mean over proteins of assay-level Spearman), unitless0.4110.439VESPA
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, Other eukaryote proteins: mean over proteins of assay-level Spearman), unitless0.4860.503VESPA
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, Prokaryote proteins: mean over proteins of assay-level Spearman), unitless0.4390.474VESPA
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, Stability assays: mean over proteins of assay-level Spearman), unitless0.4760.5VESPA
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, Virus proteins: mean over proteins of assay-level Spearman), unitless0.3580.443VESPA
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, mean over selection types of the per-type mean over proteins of assay-level Spearman (all 217 assays)), unitless0.4190.435VESPA
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, variants with 1 substitution: mean over protein and selection-type groups of assay-level Spearman), unitless0.4050.435VESPA
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, variants with 2 substitutions: mean over protein and selection-type groups of assay-level Spearman), unitless0.2630.181DeepSequence
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, variants with 3 substitutions: mean over protein and selection-type groups of assay-level Spearman), unitless0.3140.348VESPA
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, variants with 4 substitutions: mean over protein and selection-type groups of assay-level Spearman), unitless0.3220.308DeepSequence
ProteinGym v1.3 zero-shot DMS substitutionsProteinGym DMS substitution assays at commit 144fe22 (217 assays)Spearman (ProteinGym zero-shot DMS substitutions, variants with 5 or more substitutions: mean over protein and selection-type groups of assay-level Spearman), unitless0.3780.328DeepSequence
ProteinGym AMFR official zero-shot Spearman snapshotProteinGym AMFR 4G3O official snapshot cohortSpearman, unitless0.4070.254DeepSequence
Comparisons in Livesey and Marsh 2025 (7)
ProtocolDatasetMetricDeepSequenceVESPAHigher
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), percent65.968.7VESPA
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), percent76.671.3DeepSequence
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), percent17.317.3Tie
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), percent73.569.5DeepSequence
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), percent78.472.6DeepSequence
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), percent78.469.5DeepSequence
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), percent77.564.8DeepSequence

What disagrees

studies
2
Compared
DeepSequence, VESPA
Study that disagrees
Other studies
Rule
two-study-conflict; different-task
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.

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