AetherXeno: an allele-resolved receptor-occupancy atlas for regulatory pharmacogenomics

Abstract

Motivation: Interpreting noncoding pharmacogenomic variants requires identifying the regulatory program that may be perturbed and the direction of the effect, information not supplied by population frequency or general regulatory annotations. Results: We developed AetherXeno, an allele-resolved atlas that scores all substitutions across 8,691 experimentally supported elements for PXR, FXR and AhR and connects 17.27 million variants to evidence matched by exact allele. Across the six paired comparisons, the gain in Spearman correlation ranged from 0.039 to 0.334. Every regional bootstrap interval excluded zero. Homology exclusion preserved these findings, while motif core and liver expression enrichment supported biological organization of the score landscape. The browser, programmatic interface and bulk files expose the same versioned records from individual variants to cohort analyses. Availability and implementation: The web resource is available at https://aetherxeno.org and the versioned data at doi:10.5281/zenodo.20753827.