# Borzoi

Super-enhancers could previously be defined only by stitching epigenomic peaks such as H3K27ac, so unprofiled cell states were out of reach and the underlying sequence grammar stayed unread. Borzoi-SE recasts super-enhancer discovery as cell-type-resolved genomic object detection over 524-kb sequences, returning super-enhancer probabilities and boundaries across 90 human cell and tissue lineages. On held-out chromosomes it reached a region-level PR-AUC of 0.643 and F1 of 0.498, against ceilings of about 0.34 and 0.15 for four fragment-based baselines; in silico ablation of the β-globin super-enhancer ranked HS2 as the dominant hub, and CRISPRi silencing of HS2 reduced chromatin accessibility across the locus by 35% to 85%.

Super-enhancers could previously be defined only by stitching epigenomic peaks such as H3K27ac, so unprofiled cell states were out of reach and the underlying sequence grammar stayed unread. Borzoi-SE recasts super-enhancer discovery as cell-type-resolved genomic object detection over 524-kb sequences, returning super-enhancer probabilities and boundaries across 90 human cell and tissue lineages. On held-out chromosomes it reached a region-level PR-AUC of 0.643 and F1 of 0.498, against ceilings of about 0.34 and 0.15 for four fragment-based baselines; in silico ablation of the β-globin super-enhancer ranked HS2 as the dominant hub, and CRISPRi silencing of HS2 reduced chromatin accessibility across the locus by 35% to 85%.

Across 27 UK Biobank traits, variant scores from genomic foundation models (GFMs) did not yield more common-variant loci, either alone or added to standard functional annotations. AlphaGenome and Borzoi alone raised locus discovery by median 1.8% and 3.8%, below baselineLD's 5.1%, while GPN-Star reduced it. Combined with baselineLD, locus counts changed by a median of −0.1% to 0.2%, suggesting the models largely recapture regulatory information already in the standard annotations.

Across 27 UK Biobank traits, variant scores from genomic foundation models (GFMs) did not yield more common-variant loci, either alone or added to standard functional annotations. AlphaGenome and Borzoi alone raised locus discovery by median 1.8% and 3.8%, below baselineLD's 5.1%, while GPN-Star reduced it. Combined with baselineLD, locus counts changed by a median of −0.1% to 0.2%, suggesting the models largely recapture regulatory information already in the standard annotations.