{
  "abstract": "Helicobacter pylori (Hp) infects over 40% of the world population and causes most cases of gastric cancer worldwide, yet fundamental questions about its within-host genetic diversity remain unresolved. Decades of work on Hp genomics depends on culturing clinical isolates, which can distort within-host genetic heterogeneity that informs Hp virulence and antimicrobial resistance. Culture-free alternatives have been limited by the extremely low Hp abundance in gastric tissue (usually 10-3 to 10-7 of total genomic DNA), making direct metagenomics prohibitively expensive and existing enrichment strategies insufficient for whole-genome recovery. Here we develop ultra-sensitive Hp sequencing (uHp-seq) for reconstructing Hp genomes directly from gastric biopsies. uHp-seq achieves a thousand-fold Hp DNA enrichment and recovers near-complete genomes across samples spanning orders of magnitude in Hp abundance. Notably, individual hosts may harbor multiple co-existing Hp strains or cagA EPIYA variants with different oncogenic potential. Resistance-associated variants for six commonly used antibiotics are resolved with greater accuracy than PCR-based and probe-based commercial panels. Applied to minimally invasive gastric string samples, uHp-seq delivers reliable resistance profiles without endoscopy, opening a path to genome-guided Hp eradication.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "name": "Y. Liu"
    },
    {
      "name": "M. Ni"
    },
    {
      "name": "X.-S. Zhang"
    },
    {
      "name": "J. Bass"
    },
    {
      "name": "P. Deshpande"
    },
    {
      "name": "J. Romero-Gallo"
    },
    {
      "name": "H. Chen"
    },
    {
      "name": "Y. Fan"
    },
    {
      "name": "D. Wang"
    },
    {
      "name": "W. Qiao"
    },
    {
      "name": "Y. Zhang"
    },
    {
      "name": "E. A. Mead"
    },
    {
      "name": "E. Dias-Neto"
    },
    {
      "name": "A. Corvalan"
    },
    {
      "name": "R. Brody"
    },
    {
      "name": "C. M. Camargo"
    },
    {
      "name": "W. Szymczak"
    },
    {
      "name": "A. D. Klion"
    },
    {
      "name": "R. M. Peek"
    },
    {
      "name": "M. J. Blaser"
    },
    {
      "affs": [
        0
      ],
      "name": "G. Fang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cdjyaajjq5xtv.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.23.26365955",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.23.26365955v1.full",
  "id": "cdjyaajjq5xtv",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.23.26365955v1",
  "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": [
    [
      "medrxiv",
      "infectious diseases"
    ],
    [
      "openalex",
      "2746|Helicobacter pylori-related gastroenterology studies"
    ]
  ],
  "openalex": "W7223674215",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.23.26365955v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cdjyaajjq5xtv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:50Z",
      "native_id": "10.64898/2026.10.23.26365955",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.23.26365955v2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:infectious diseases",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Culture-free Helicobacter pylori genomics reveals within-host virulence heterogeneity and antibiotic resistance",
  "title_text": "Culture-free Helicobacter pylori genomics reveals within-host virulence heterogeneity and antibiotic resistance",
  "type": "preprint",
  "updated_at": "2026-11-05T00:20:36Z",
  "url": "https://research.draconitic.com/paper/cdjyaajjq5xtv",
  "venue": "medRxiv",
  "versions": []
}