Individual skill
tooluniverse-variant-predictor-dms-validation
Validate a variant-effect predictor (AlphaMissense, ESM-C SAE, ESM logits, EVE, conservation scores, or any per-variant numeric score) against experimental deep mutational scanning (DMS) data. Computes per-variant predictor scores, splits variants into neutral vs disruptive groups by DMS effect, runs a Mann-Whitney U test on the predictor scores, and sweeps the stratification thresholds for robustness. Use when you need to know whether a predictor's scores track real functional disruption on a specific protein.
skills/tooluniverse-variant-predictor-dms-validation/SKILL.md
Source commit 5598a9fc97e32964fe9b703818e7d0747142f179
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- Apache-2.0
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# Variant-effect predictor benchmarking against DMS
The core user question: **"I have a variant-effect predictor — does it actually
correlate with experimental DMS measurements on this protein?"**
The predictor can be anything that assigns a numeric score to single missense
variants:
- ESM-C 6B Sparse Autoencoder (SAE) feature drops at the mutation site
- AlphaMissense pathogenicity scores
- ESM logits-based variant scoring (`ESM_score_sequence`)
- EVE / EVE++ scores
- Conservation scores (ConSurf, Rate4Site)
- DynaMut2 ΔΔG predictions
- A custom in-house model