{
  "abstract": "Lentiviral vectors (LVs) are clinically established for SCID-X1 gene therapy, yet the quantitative epigenomic and spatial determinants governing integration targeting and long-term clonal persistence across chromosomes remain incompletely characterized. Using clinical multi-omics datasets from SCID-X1 trials, we curated 274,959 unique clinical integration sites (VIS) across 276,839 clonal records from 10 patients (hg38). Balanced against length-weighted genomic controls (total N = 549,918), five epigenomic and topological features were modeled. We evaluated Logistic Regression, XGBoost, and a Deep Genomic ResNet using inner 5-fold chromosome-grouped cross-validation and evaluation on held-out test chromosomes (chr19-22, chrX). Statistical uncertainty was quantified via 1-Mb block-bootstrap (5,000 replicates) and 1-Mb block permutations (10,000 replicates). On held-out chromosomes, Deep ResNet achieved an ROC-AUC of 0.7857 [95% CI: 0.7672-0.8029] and PR-AUC of 0.8027 [95% CI: 0.7640-0.8337] over the 0.5755 prevalence baseline, outperforming linear baselines. 1-Mb block permutations confirmed significant proximity to scATAC-seq peaks (Cliff's {delta}=-0.3364, P_perm<0.0001) and TSSs ({delta}=-0.2446, P_perm<0.0001), alongside 82.71% gene body overlap (OR = 3.47). Targeted analysis showed 99.91% of VIS reside distal (>100 kb) from proto-oncogenes without proximal enrichment (OR = 1.05, P = 0.617). Furthermore, longitudinal tracking identified 79,587 persistent clones ([≥]2 time points), which exhibited a significant 31% depletion near proto-oncogenes (OR = 0.69, P = 0.014). Compact topological and epigenomic features robustly predict lentiviral integration without spatial data leakage. The long-term depletion of persistent clones near oncogenes confirms the insertional safety of SIN lentiviral gene therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cellular and Molecular Biology, Faculty of Basic Sciences, Islamic Azad University, Ardabil Branch, Ardabil, 56131, Iran"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "H. Saber"
    },
    {
      "name": "Z. Mousavipour"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1q593jwje1cxj.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.05.749598",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.05.749598v1.full",
  "id": "1q593jwje1cxj",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.05.749598v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ],
    [
      "openalex",
      "1311|Virus-based gene therapy research"
    ]
  ],
  "openalex": "W7212418106",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.05.749598v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1q593jwje1cxj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:47Z",
      "native_id": "10.64898/2026.09.05.749598",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.05.749598v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Explainable Machine Learning and Epigenomic Profiling Decipher the Topological Determinants of Lentiviral Integration and Longitudinal Persistence in SCID-X1 Gene Therapy",
  "title_text": "Explainable Machine Learning and Epigenomic Profiling Decipher the Topological Determinants of Lentiviral Integration and Longitudinal Persistence in SCID-X1 Gene Therapy",
  "type": "preprint",
  "updated_at": "2026-10-30T12:21:47Z",
  "url": "https://research.draconitic.com/paper/1q593jwje1cxj",
  "venue": "bioRxiv",
  "versions": []
}