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).
- 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.
| Paper | Role | Ranks DeepSequence higher | Ranks VESPA higher | Ties |
|---|---|---|---|---|
| ProteinGym: Large-Scale Benchmarks for Protein Fitness Prediction and Design and 6 more records · DOI | Agrees | 4 | 13 | 2 |
| Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML) and 1 more record · DOI | Agrees | 5 | 1 | 1 |
Comparisons in ProteinGym (19)
| Protocol | Dataset | Metric | DeepSequence | VESPA | Higher |
|---|---|---|---|---|---|
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym DMS substitution assays at commit 144fe22 (217 assays) | Spearman (ProteinGym zero-shot DMS substitutions, Activity assays: mean over proteins of assay-level Spearman), unitless | 0.455 | 0.468 | VESPA |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym DMS substitution assays at commit 144fe22 (217 assays) | Spearman (ProteinGym zero-shot DMS substitutions, Binding assays: mean over proteins of assay-level Spearman), unitless | 0.363 | 0.366 | Tie |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym DMS substitution assays at commit 144fe22 (217 assays) | Spearman (ProteinGym zero-shot DMS substitutions, Expression assays: mean over proteins of assay-level Spearman), unitless | 0.39 | 0.404 | VESPA |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym 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), unitless | 0.474 | 0.484 | VESPA |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym DMS substitution assays at commit 144fe22 (217 assays) | Spearman (ProteinGym zero-shot DMS substitutions, Human proteins: mean over proteins of assay-level Spearman), unitless | 0.443 | 0.44 | Tie |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym 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), unitless | 0.37 | 0.42 | VESPA |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym 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), unitless | 0.431 | 0.455 | VESPA |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym DMS substitution assays at commit 144fe22 (217 assays) | Spearman (ProteinGym zero-shot DMS substitutions, Organismal fitness assays: mean over proteins of assay-level Spearman), unitless | 0.411 | 0.439 | VESPA |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym DMS substitution assays at commit 144fe22 (217 assays) | Spearman (ProteinGym zero-shot DMS substitutions, Other eukaryote proteins: mean over proteins of assay-level Spearman), unitless | 0.486 | 0.503 | VESPA |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym DMS substitution assays at commit 144fe22 (217 assays) | Spearman (ProteinGym zero-shot DMS substitutions, Prokaryote proteins: mean over proteins of assay-level Spearman), unitless | 0.439 | 0.474 | VESPA |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym DMS substitution assays at commit 144fe22 (217 assays) | Spearman (ProteinGym zero-shot DMS substitutions, Stability assays: mean over proteins of assay-level Spearman), unitless | 0.476 | 0.5 | VESPA |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym DMS substitution assays at commit 144fe22 (217 assays) | Spearman (ProteinGym zero-shot DMS substitutions, Virus proteins: mean over proteins of assay-level Spearman), unitless | 0.358 | 0.443 | VESPA |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym 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)), unitless | 0.419 | 0.435 | VESPA |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym 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), unitless | 0.405 | 0.435 | VESPA |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym 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), unitless | 0.263 | 0.181 | DeepSequence |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym 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), unitless | 0.314 | 0.348 | VESPA |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym 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), unitless | 0.322 | 0.308 | DeepSequence |
| ProteinGym v1.3 zero-shot DMS substitutions | ProteinGym 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), unitless | 0.378 | 0.328 | DeepSequence |
| ProteinGym AMFR official zero-shot Spearman snapshot | ProteinGym AMFR 4G3O official snapshot cohort | Spearman, unitless | 0.407 | 0.254 | DeepSequence |
Comparisons in Livesey and Marsh 2025 (7)
| Protocol | Dataset | Metric | DeepSequence | VESPA | Higher |
|---|---|---|---|---|---|
| Livesey and Marsh 2025 clinical benchmark: pairwise AUROC win rate, ClinVar pathogenic versus gnomAD missense | Livesey 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), percent | 65.9 | 68.7 | VESPA |
| Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, all 36 DMS sets | Livesey 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), percent | 76.6 | 71.3 | DeepSequence |
| Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, all 36 DMS sets | Livesey 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), percent | 17.3 | 17.3 | Tie |
| Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, direct assays only | Livesey 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), percent | 73.5 | 69.5 | DeepSequence |
| Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, indirect assays only | Livesey 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), percent | 78.4 | 72.6 | DeepSequence |
| Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions only | Livesey 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), percent | 78.4 | 69.5 | DeepSequence |
| Livesey and Marsh 2025 DMS benchmark: pairwise |Spearman| win rate, SNV-accessible substitutions with gaps filled | Livesey 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), percent | 77.5 | 64.8 | DeepSequence |
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.
Finding discrepancy-57a10eb53a2a403c · All contested results · How findings are made and followed up