{
  "abstract": "Research on the potential use of seminal fluid as a liquid biopsy for prostate cancer detection has been limited due to challenges associated with acquisition of this bodily fluid in clinical studies. Here we sought to expand on our previous analysis, which demonstrated high levels of prostate-derived cell free DNA (cfDNA) in seminal fluid in presumed healthy individuals, to a much larger cohort that included participants with prostate cancer. A total of 279 men scheduled for prostate biopsy were enrolled over 4 months across 12 sites. Prior to their biopsy, participants mailed a seminal fluid sample collected at home to the laboratory, from which cfDNA was extracted and underwent methylation analysis. Consistent with our earlier study in healthy individuals, we observed an abundance of high molecular weight (HMW) cfDNA in all samples. Tissue-of-origin deconvolution revealed that granulocytes and sperm were the principal contributors to seminal fluid cfDNA, while prostate-derived cfDNA was present at abundances readily detectable with current technologies. The nucleosomal fraction was very pronounced in some but not all samples and was determined to be correlated with the relative sperm signal. The sperm signal was also observed to be associated with an increase in small insert sizes (< 125 bp) in the sequenced libraries. Unsupervised clustering revealed two distinct populations driven by the abundance of sperm and granulocytes. Since summarizing at the genomic region level confounded tissues of different origins, fragment-level DNA methylation features were used to characterize and quantify the prostate cancer related signal, and features associated with clinically significant prostate cancer were identified. This study expands on our previous work to further characterize seminal fluid and highlights its potential as a promising liquid biopsy medium for the detection and monitoring of clinically significant prostate cancer.",
  "abstract_shown": true,
  "affiliations": [
    "Fellow Health Inc., San Leandro, California, United States of America",
    "Dept. of Urology, University of California, San Francisco, California, United States of America",
    "Department of Clinical Research, Urology Clinics of North Texas, Dallas, Texas, United States of America",
    "Comprehensive Urology, Los Angeles, California, United States of America",
    "Integrated Medical Professionals, New York, New York, United States of America",
    "MidLantic Urology, Bala Cynwyd, Pennsylvania, United States of America"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jennifer Geis"
    },
    {
      "affs": [
        1
      ],
      "name": "James F. Smith"
    },
    {
      "affs": [
        2
      ],
      "name": "Tara Maddala"
    },
    {
      "affs": [
        3
      ],
      "name": "Greg Thoreson"
    },
    {
      "affs": [
        4
      ],
      "name": "Kiarash Michel"
    },
    {
      "affs": [
        5
      ],
      "name": "Jed Kaminetsky"
    },
    {
      "name": "Laurence Belkoff"
    },
    {
      "name": "Stephanie Huang"
    },
    {
      "name": "Bailey Griscom"
    },
    {
      "name": "James C. Hart"
    },
    {
      "name": "Shellie Bench"
    },
    {
      "name": "Hamisha Ardalani"
    },
    {
      "name": "Laura Rivas-Yepes"
    },
    {
      "name": "Daniel Civello"
    },
    {
      "name": "Kim M. Clark-Langone"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dttctgdnpdvw3.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0356387",
  "fulltext_url": null,
  "id": "dttctgdnpdvw3",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0356387",
  "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",
      "1306|Cancer Genomics and Diagnostics"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Body fluids/Semen"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Exocrine glands/Prostate gland"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Nucleic acids/DNA/DNA modification/DNA methylation"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/Granulocytes"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Germ cells/Sperm"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/Granulocytes"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Chromosome biology/Chromatin/Chromatin modification/DNA methylation"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/DNA/DNA modification/DNA methylation"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Epigenetics/Chromatin/Chromatin modification/DNA methylation"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Epigenetics/DNA modification/DNA methylation"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/Chromatin/Chromatin modification/DNA methylation"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/DNA modification/DNA methylation"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune cells/White blood cells/Granulocytes"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Body fluids/Semen"
    ],
    [
      "plos",
      "/Engineering and technology/Equipment/Optical equipment/Prisms"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Body fluids/Semen"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Exocrine glands/Prostate gland"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune cells/White blood cells/Granulocytes"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Genitourinary tract tumors/Prostate cancer"
    ],
    [
      "plos",
      "/Medicine and health sciences/Surgical and invasive medical procedures/Reproductive system procedures/Vasectomy"
    ],
    [
      "plos",
      "/Medicine and health sciences/Surgical and invasive medical procedures/Surgical excision/Vasectomy"
    ],
    [
      "plos",
      "/Medicine and health sciences/Urology/Prostate diseases/Prostate cancer"
    ]
  ],
  "openalex": "W7212072064",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0356387&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-09",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/dttctgdnpdvw3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:56Z",
      "native_id": "10.1371/journal.pone.0356387",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0356387"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "plos:genetics",
      "subfield": "genetics-genomics"
    },
    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
    }
  ],
  "title": "Uncovering the diagnostic potential of seminal fluid beyond fertility: cfDNA methylation analysis for the detection of clinically significant prostate cancer",
  "title_text": "Uncovering the diagnostic potential of seminal fluid beyond fertility: cfDNA methylation analysis for the detection of clinically significant prostate cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:56Z",
  "url": "https://research.draconitic.com/paper/dttctgdnpdvw3",
  "venue": "PLOS One",
  "versions": []
}