# New Preprint: Calibration of AlphaGenome Regulatory Effect Scores

**URL:** <https://www.alphagenomecommunity.com/t/new-preprint-calibration-of-alphagenome-regulatory-effect-scores/950>\
**Category:** Community\
**Created:** [July 29, 2026, 6:09pm UTC](https://www.alphagenomecommunity.com/t/new-preprint-calibration-of-alphagenome-regulatory-effect-scores/950 "2026-07-29T18:09:32Z")\
**Posts on this page:** 1\
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**Author:** ![Israel\_Nadal\_Vidal](https://yyz2.discourse-cdn.com/watermelon/user_avatar/www.alphagenomecommunity.com/israel_nadal_vidal/32/292_2.png) [@Israel\_Nadal\_Vidal](https://www.alphagenomecommunity.com/u/Israel_Nadal_Vidal)\
**Post date:** [July 29, 2026, 6:09pm UTC](https://www.alphagenomecommunity.com/t/new-preprint-calibration-of-alphagenome-regulatory-effect-scores/950/1 "2026-07-29T18:09:32Z")

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Hello everyone,

I wanted to share a preprint I have just published that evaluates the calibration of AlphaGenome regulatory effect scores against experimental saturation mutagenesis data.

The study analyzes **20,549 SNVs across 15 regulatory elements** and compares AlphaGenome predictions with experimentally measured regulatory effects.

The main observation is that the raw effect-score scale appears to be **distance-dependent** :

- Promoter variants tend to have over-dispersed predicted effects.
- Distal enhancer variants tend to have compressed predicted effects.
- As a consequence, raw scores from different loci may not be directly comparable using a single genome-wide threshold.

Importantly, this is **not intended as a criticism of AlphaGenome** , which I believe represents a major advance for regulatory genomics. Rather, the work suggests that **local calibration** may be necessary before comparing scores across different genomic regions.

The paper also includes:

- comparison against saturation mutagenesis experiments
- per-locus calibration analysis
- coordinate/allele verification pipeline
- released analysis code and validation framework

I would greatly appreciate any feedback, comments, or suggestions from the community.

Preprint:

[https://www.preprints.org/manuscript/202607.1417](https://www.preprints.org/manuscript/202607.1417)

Thank you to the AlphaGenome team for making such an exciting model publicly available.