{
  "abstract": "Microsatellite instability (MSI) is a key biomarker of mismatch repair deficiency and response to immunotherapy, yet most existing genomic detection methods are optimized for short-read sequencing and rely on a panel of homopolymer markers, limiting the ability to characterize genome-wide and motif-specific patterns of instability. Here we present Owl, a bioinformatic tool for quantifying MSI from long-read (PacBio) genomic data. Owl leverages a genome-wide marker set of more than 140,000 microsatellite repeats ranging from 1–6 bp in length to measure MSI across a phased genome. Using a wrap-around alignment algorithm, Owl constructs repeat-length distributions at each marker site and flags somatic instability using the coefficient of variation. We applied Owl to screen for markers with stable coverage, phasing, and baseline variation across 131 diverse genomes from the Human Pangenome Reference Consortium, where Owl scores ranged from 1.4% to 5.4% of markers exceeding the instability threshold. When applied to cancer cell lines and one diffuse astrocytoma tumor-normal pair, Owl identified six MSI genomes with 10–27% unstable markers and showed close concordance with an Illumina DRAGEN MSI assay for the astrocytoma sample. Motif-level analyses revealed shared enrichment of short homopolymer and dinucleotide (A- and AT-rich) repeats across MSI cancers. Owl is implemented in Rust and integrated into the PacBio HiFi Somatic workflow, providing a scalable framework for MSI analysis from long-read sequencing focused on repeat instability specifically in tumor samples.",
  "abstract_shown": true,
  "affiliations": [
    "PacBio, Menlo Park, California, United States of America",
    "Children’s Mercy Hospital, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, United States of America",
    "University of Southern California, Los Angeles, California, United States of America",
    "Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, United States of America",
    "Fred Hutch Cancer Center, Seattle, Washington, United States of America",
    "Duke-NUS Medical School, Singapore, Singapore",
    "Genome Institute of Singapore, Singapore, Singapore",
    "Precision Health Research Singapore, Singapore, Singapore",
    "Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children’s Research Institute, Seattle, Washington, United States of America",
    "Department of Pediatrics, University of Washington, Seattle, Washington, United States of America"
  ],
  "article_type": "Software",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zev Kronenberg"
    },
    {
      "affs": [
        1
      ],
      "name": "Byunggil Yoo"
    },
    {
      "affs": [
        2
      ],
      "name": "Khi Pin Chua"
    },
    {
      "affs": [
        3
      ],
      "name": "Mark J. P. Chaisson"
    },
    {
      "affs": [
        4
      ],
      "name": "Lisa Lansdon"
    },
    {
      "affs": [
        5
      ],
      "name": "William J. Rowell"
    },
    {
      "affs": [
        6
      ],
      "name": "Guilherme de Sena Brandine"
    },
    {
      "affs": [
        7
      ],
      "name": "Jocelyne Bruand"
    },
    {
      "affs": [
        8
      ],
      "name": "Egor Dolzhenko"
    },
    {
      "affs": [
        9
      ],
      "name": "Kobe Ikegami"
    },
    {
      "name": "Jay Sarthy"
    },
    {
      "name": "Kie Kyon Huang"
    },
    {
      "name": "Patrick Tan"
    },
    {
      "name": "Shruti Bhise"
    },
    {
      "name": "Everett Fan"
    },
    {
      "name": "Mark Mendoza"
    },
    {
      "name": "Emily O’Donnell"
    },
    {
      "name": "Tomi Pastinen"
    },
    {
      "name": "Elizabeth R. Lawlor"
    },
    {
      "name": "Scott N. Furlan"
    },
    {
      "name": "Midhat S. Farooqi"
    },
    {
      "name": "Michael A. Eberle"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bsvmncmtc2yhm.bib",
  "cited_by": 2,
  "doi": "10.1371/journal.pcbi.1014423",
  "fulltext_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014423",
  "id": "bsvmncmtc2yhm",
  "issns": [
    "1553-7358"
  ],
  "landing_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014423",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2734|Genetic factors in colorectal cancer"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Genomic medicine/Cancer genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Eukaryota/Animals/Vertebrates/Amniotes/Birds/Raptors/Owls"
    ],
    [
      "plos",
      "/Biology and life sciences/Zoology/Animals/Vertebrates/Amniotes/Birds/Raptors/Owls"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Basic cancer research/Cancer genomics"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Colorectal cancer"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Gastrointestinal tumors/Gastric cancer"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Genitourinary tract tumors/Prostate cancer"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Malignant tumors"
    ],
    [
      "plos",
      "/Medicine and health sciences/Urology/Prostate diseases/Prostate cancer"
    ],
    [
      "plos",
      "/Research and analysis methods/Database and informatics methods/Bioinformatics/Sequence analysis/Sequence motif analysis"
    ]
  ],
  "openalex": "W7134938986",
  "pdf_url": "https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1014423&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-02",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/bsvmncmtc2yhm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:02Z",
      "native_id": "10.1371/journal.pcbi.1014423",
      "source": "plos",
      "url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014423"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "plos:oncology",
      "subfield": "oncology"
    }
  ],
  "title": "Hunting for microsatellite instability in long-read data with Owl",
  "title_text": "Hunting for microsatellite instability in long-read data with Owl",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:02Z",
  "url": "https://research.draconitic.com/paper/bsvmncmtc2yhm",
  "venue": "PLOS Computational Biology",
  "versions": []
}