{
  "abstract": "Circulating fetal cfDNA is the analyte of a screening test used by millions of pregnant women annually. However, low fetal fraction limits current testing. Fetal cfDNA can be enriched via hypomethylation, but the informative sites require a first-trimester fetal methylome reference. Here we sequenced fetal cfDNA (median purity 94.7%) derived from discarded media from cultured chorionic villus biopsies (n=30) and assembled a first-trimester methylome across 26M CpG methylation sites at a median depth of 207x. We then built an analytical enrichment model that identified millions of CpG markers and assigned predicted enrichment scores. Guided by this model, we adapted epiSIFT as a genome-wide assay selective for unmethylated DNA molecules. In 28 prenatal plasma cases, epiSIFT raised the median fetal fraction from 5.1% to 28.4% (5.6-fold gain) using the top eighth of markers. These findings establish a first-trimester fetal cfDNA methylome reference and demonstrate epigenetic enrichment of the fetal genome.",
  "abstract_shown": true,
  "affiliations": [
    "Stanford University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "T. Liao"
    },
    {
      "name": "C. Rao"
    },
    {
      "name": "S. Iyer"
    },
    {
      "name": "S. C. Ding"
    },
    {
      "name": "J. Yu"
    },
    {
      "name": "Z. Lui"
    },
    {
      "name": "C. Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "W. Gu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ejpysmchpjr5d.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.20.760549",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.20.760549v1.full",
  "id": "ejpysmchpjr5d",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.20.760549v1",
  "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",
      "genomics"
    ],
    [
      "openalex",
      "2735|Prenatal Screening and Diagnostics"
    ]
  ],
  "openalex": "W7223552895",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.20.760549v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-20",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ejpysmchpjr5d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:37Z",
      "native_id": "10.64898/2026.10.20.760549",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.20.760549v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genomics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Early Prenatal Cell-Free DNA Methylation Landscape Informs Epigenetic Purification of the Circulating Fetal Genome",
  "title_text": "Early Prenatal Cell-Free DNA Methylation Landscape Informs Epigenetic Purification of the Circulating Fetal Genome",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:37Z",
  "url": "https://research.draconitic.com/paper/ejpysmchpjr5d",
  "venue": "bioRxiv",
  "versions": []
}