{
  "abstract": "Background: Archival biobanks of formalin-fixed paraffin-embedded (FFPE) specimens represent a vast and underused resource for retrospective molecular studies linked to clinical follow-up. However, fixation-induced chemical modification and nucleic acid fragmentation limit scalable genomic and transcriptomic profiling. FFPE-CUTAC (Cleavage Under Targeted Accessible Chromatin) is an RNA polymerase II-targeted DNA assay specifically designed to profile regulatory activity in FFPE tissue. Here, we assess its archival robustness, information content, compatibility with RNA-seq, and ability to recover copy-number alterations. Results: In meningioma and breast cancer cohorts, we benchmarked FFPE-CUTAC against matched fresh-frozen RNA-seq, FFPE RNA-seq and FFPE whole-genome sequencing. For FFPE specimens spanning up to 25 years, FFPE-CUTAC showed no systematic collection-year-associated decline in library yield or signal-quality metrics. In contrast, FFPE RNA-seq is more affected by the FFPE tissue degradation and specimen age on read composition, gene-body coverage, and gene detection. By measuring RNA polymerase II occupancy on chromatin rather than mature RNA abundance, FFPE-CUTAC is less constrained by transcript half-life, polyadenylation or transcript-capture design. FFPE-CUTAC extends beyond gene regions to non-coding regulatory elements, while the shared gene-level signals supported its integration with existing RNA-seq cohorts for large-scale, long-term clinical association study. FFPE-CUTAC libraries also retain DNA dosage information and can be used to recover chromosome-arm gain, loss and intact states with 96% concordance to matched whole-genome sequencing. Conclusions: By converting routinely preserved pathology sections into integrated regulatory and copy-number profiles, FFPE-CUTAC provides a practical foundation for constructing clinically annotated disease maps to support molecular stratification, prognostic modeling and treatment-association studies.",
  "abstract_shown": true,
  "affiliations": [
    "The University of Texas MD Anderson Cancer Center"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "Y. Niu"
    },
    {
      "name": "Q. Xu"
    },
    {
      "name": "C. Y. Mak"
    },
    {
      "name": "Y. Xu"
    },
    {
      "name": "A. Parmar"
    },
    {
      "name": "A. Zevin"
    },
    {
      "name": "N. Khyzha"
    },
    {
      "name": "R. Paranal"
    },
    {
      "name": "E. Holland"
    },
    {
      "name": "K. Ahmad"
    },
    {
      "name": "S. Henikoff"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. Zheng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e626sfbzsrv7e.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.21.753320",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753320v1.full",
  "id": "e626sfbzsrv7e",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753320v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W7214004554",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753320v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e626sfbzsrv7e.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:57Z",
      "native_id": "10.64898/2026.09.21.753320",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753320v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "FFPE-CUTAC: A Single Assay, Multiple Layers",
  "title_text": "FFPE-CUTAC: A Single Assay, Multiple Layers",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:57Z",
  "url": "https://research.draconitic.com/paper/e626sfbzsrv7e",
  "venue": "bioRxiv",
  "versions": []
}