MetaRNN and VARITY: 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 VARITY above MetaRNN in 6 of 7 comparisons; An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers ranks MetaRNN above VARITY in 3 of 4 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
3 papers rank MetaRNN above VARITY in 5 of their 14 comparisons and VARITY higher in 7; 2 are ties. Of those papers, Livesey and Marsh 2025 ranks VARITY higher on its own (6 of 7).
- Rank MetaRNN higher (2): An openly licensed benchmark…, ProteinGym
- Rank VARITY 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.
| Paper | Role | Ranks MetaRNN higher | Ranks VARITY higher | Ties |
|---|---|---|---|---|
| Livesey and Marsh 2025, Genome Biology 26:104 (Europe PMC full text XML) and 1 more record · DOI | Agrees | 1 | 6 | 0 |
| An openly licensed benchmark and per-gene calibration map for missense pathogenicity predictors on activating cancer drivers and 1 more record · DOI | Agrees | 3 | 1 | 2 |
| ProteinGym: Large-Scale Benchmarks for Protein Fitness Prediction and Design and 6 more records · DOI | Agrees | 1 | 0 | 0 |
Comparisons in Livesey and Marsh 2025 (7)
| Protocol | Dataset | Metric | MetaRNN | VARITY | 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 | 82.2 | 63.7 | MetaRNN |
| 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 | 73.2 | 80.5 | VARITY |
| 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 | 16.6 | 27.9 | VARITY |
| 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 | 74.8 | 77.4 | VARITY |
| 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 | 71.9 | 83.7 | VARITY |
| 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 | 73.2 | 80.5 | VARITY |
| 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 | 74.1 | 80.5 | VARITY |
Comparisons in An openly licensed benchmark… (6)
Comparisons in ProteinGym (1)
| Protocol | Dataset | Metric | MetaRNN | VARITY | Higher |
|---|---|---|---|---|---|
| ProteinGym clinical substitutions, supervised predictors, average AUC (commit 144fe22) | ProteinGym clinical substitution benchmark at commit 144fe22 | AUROC (ProteinGym clinical substitutions, supervised clinical predictors, Average_AUC over proteins), unitless | 0.977 | 0.918 | MetaRNN |
What disagrees
- studies
- 2
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-0fd88561eedbd7c2 · All contested results · How findings are made and followed up