{
  "abstract": "Background: Sequence-to-function models predict regulatory perturbation responses, but their added value beyond established enhancer-gene predictors and across prediction tasks remains unclear. We evaluated whole-enhancer deletion and sparse variant responses in human astrocytes. Results: We analyzed 2,307 CRISPR-interference-tested relations, including 133 expression-decreasing hits. Adding deletion responses increased fully nested EGrf average precision from 0.5475 to 0.6137. The paired increment was 0.0662 (enhancer-cluster 95% interval 0.0144-0.1181). In a separate exploratory analysis, sparse Atlas responses were combined with seven-input logistic and random-forest comparators by equal-weight rank fusion. Atlas magnitude fusion exceeded absolute-deletion fusion by 0.0519 and 0.0637 in average precision. Enhancer-cluster 95% intervals were 0.0098-0.0957 and 0.0220-0.1094, respectively. Standalone Atlas magnitude reached average precision 0.5570, but its advantage over absolute deletion remained uncertain. Signed Atlas fusion performed worse than either comparator alone. Incremental value for within-enhancer target choice and in the external WTC11 MHC evaluation remained uncertain. The reported performance intervals use one-way clustering of fixed predictions; Atlas analyses were exploratory within the same cohort. Conclusions: In AstroREG, whole-enhancer deletion responses increased observed retrieval performance beyond a fully nested chromatin-based predictor. Sparse variant responses were more informative as magnitudes than as signed averages. Improved within-enhancer target choice and external transfer were not established.",
  "abstract_shown": true,
  "affiliations": [
    "University of Washington"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Z. Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "R. Huang"
    },
    {
      "name": "J. Han"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/46r6hqya02dws.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.14.744988",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.14.744988v2.full",
  "id": "46r6hqya02dws",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.14.744988v2",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genomics"
    ],
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W7203780767",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.14.744988v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/46r6hqya02dws.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:39Z",
      "native_id": "10.64898/2026.08.14.744988",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.14.744988v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genomics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Response representation shapes AlphaGenome enhancer-gene prediction in human astrocytes",
  "title_text": "Response representation shapes AlphaGenome enhancer-gene prediction in human astrocytes",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:39Z",
  "url": "https://research.draconitic.com/paper/46r6hqya02dws",
  "venue": "bioRxiv",
  "versions": []
}