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Documentation
How the atlas is built, what each field means, and how to cite it. For the live REST API and an interactive console, see the API page. For the external resources we link to, see Databases.
Data dictionary
| Field | Definition |
|---|---|
| ft_head_delta_{R} | Raw center bin sum of ALT minus REF on receptor R's CHIP_TF head |
| ft_head_delta_{R}_norm | Normalized to peak population 99th pct, clipped to [−1, 1] |
| effect_direction_{R} | LoF (< −0.1), GoF (> 0.1), or Neutral |
| ahr_exploratory | TRUE when the AhR head was trained on a single replicate at Gate 6B |
| in_{R}_peak | Variant overlaps receptor R ChIP-seq peak |
| multi_receptor_overlap | Comma list of receptors whose peaks overlap the variant |
| region_tier | receptor_confirmed (peak union) vs ATAC_only (extended) |
| gnomad_af | gnomAD v4.1 allele frequency |
| is_singleton | AF == 0 in gnomAD (private or singleton) |
Methods
ChIP-seq on PXR, FXR and AhR in primary human hepatocytes is aligned with BWA MEM, peaks called with MACS2 and converted to BigWig. The AlphaGenome trunk is frozen while a CHIP_TF head is finetuned per receptor with Adam on an L0 plus center and peak weighted loss. Variant effect is the center bin sum of ALT minus REF from predict_sequence. Validation covers gold standard recovery, a head to head comparison against Enformer and CADD, and GTEx liver eQTL enrichment.
Data availability and sources
AetherXeno is built entirely on public data. The receptor binding maps are reanalyses of published primary human hepatocyte ChIP-seq, all retrievable from their original archives. We add the finetuned variant effect layer and the cross-annotations; we credit and link every source.
| Layer | Source study | Accession | Condition |
|---|---|---|---|
| PXR ChIP-seq | Smith et al. 2014, PHH | SRR1642055/56/57 | input / DMSO / rifampicin |
| FXR ChIP-seq | Zhan et al. 2014, PHH | GSE57227 | GW4064 |
| AhR ChIP-seq (exploratory) | Bhattacharya et al. 2023, PHH | GSE205502 | TCDD, single replicate |
| Backbone model | AlphaGenome (Google DeepMind) | alphagenome | non-commercial terms, finetuned per receptor |
The variant effect predictions are AlphaGenome Output, used under the AlphaGenome Output Terms of Use (non-commercial). Cross-annotation sources and their licenses are listed on the Databases page. The full derived atlas and annotation layers are deposited on Zenodo (see Download).
Citation
AetherXeno: a regulatory variant effect atlas across three receptors for induction pharmacogenomics, in preparation. Variant effect predictions are AlphaGenome Output, subject to the AlphaGenome Output Terms of Use (non-commercial); AetherXeno annotations CC-BY-NC; code MIT. Permanent archive: Zenodo DOI at publication.