{
  "abstract": "Cancer-associated epigenetic remodeling involves a complex interplay between DNA secondary structures and covalent cytosine modifications, yet predicting endogenously folded, chromatin-constrained G-quadruplex (G4) dynamics remains challenging. Here, we develop G4SCOPE, a multi-task deep learning framework that models chromatin-associated G4 occupancy and reconstructs quantitative high-resolution CUT&Tag profiles directly from primary DNA sequence alone. We initially trained G4SCOPE on genotype-stratified G4 enriched cut&tag landscapes generated across an isogenic series of human breast epithelial cells (WT, TP53-/-, TP53-/-;BRCA1-/-, and TP53-/-;BRCA2-/-). G4SCOPE integrates convolutional motif learning with transformer self-attention to decode long-range sequence contexts. The model robustly distinguishes chromatin-associated G4s from GC-matched loci with intrinsic in vitro folding potential, generalizes across distinct breast lineages, and transfers accurately to an independent K562 cellular context. Strikingly, genotype-resolved mapping reveals a profound divergence in genome maintenance states: BRCA1 deficiency indicated a global inflation of chromatin-embedded G4 density, whereas BRCA2 loss was associated with systemic, chromosome-wide structural depletion. Furthermore, unsupervised clustering of model-derived latent sequence representations identified distinct biological G4 subclasses that occupy unique regulatory class genomic environments associated with distinct local 5-methylcytosine and 5-hydroxymethylcytosine landscapes. Together, our framework decodes the primary sequence grammar governing cell-based G4 occupancy and demonstrates that sequence-defined G4 topologies harbor intrinsic and distinct local epigenetic features.",
  "abstract_shown": true,
  "affiliations": [
    "BC Cancer Research Institute, 675 W10th Avenue, Vancouver, V5Z 1L3, Canada"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "A. Sarvar"
    },
    {
      "name": "I. Esain-Garcia"
    },
    {
      "name": "L. Melidis"
    },
    {
      "name": "D. Yap"
    },
    {
      "name": "C. O'Flanagan"
    },
    {
      "name": "V. Cerda"
    },
    {
      "name": "D. Lai"
    },
    {
      "name": "D. Tannahill"
    },
    {
      "name": "Y. Park"
    },
    {
      "name": "S. Balasubramanian"
    },
    {
      "affs": [
        0
      ],
      "name": "S. Aparicio"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1qd7d08774e1y.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.28.748631",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.28.748631v1.full",
  "id": "1qd7d08774e1y",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.28.748631v1",
  "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",
      "bioinformatics"
    ],
    [
      "openalex",
      "1312|DNA and Nucleic Acid Chemistry"
    ]
  ],
  "openalex": "W7219802655",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.28.748631v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1qd7d08774e1y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:59Z",
      "native_id": "10.64898/2026.09.28.748631",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.28.748631v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "G4SCOPE identifies sequence features and epigenetic contexts of chromatin G-quadruplexes",
  "title_text": "G4SCOPE identifies sequence features and epigenetic contexts of chromatin G-quadruplexes",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:59Z",
  "url": "https://research.draconitic.com/paper/1qd7d08774e1y",
  "venue": "bioRxiv",
  "versions": []
}