{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T18:08:24Z","timestamp":1788977304225,"version":"build-2803163510"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>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 (&lt; 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.<\/jats:p>","DOI":"10.1371\/journal.pone.0356387","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:33:20Z","timestamp":1788975200000},"page":"e0356387","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Uncovering the diagnostic potential of seminal fluid beyond fertility: cfDNA methylation analysis for the detection of clinically significant prostate cancer"],"prefix":"10.1371","volume":"21","author":[{"given":"Jennifer","family":"Geis","sequence":"first","affiliation":[{"name":"Fellow Health Inc.","place":["San Leandro, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F.","family":"Smith","sequence":"additional","affiliation":[{"name":"Fellow Health Inc.","place":["San Leandro, California, United States of America"]},{"name":"University of California","place":["San Francisco, California, United States of America"],"department":["Dept. of Urology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Maddala","sequence":"additional","affiliation":[{"name":"Fellow Health Inc.","place":["San Leandro, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2345-4473","authenticated-orcid":true,"given":"Greg","family":"Thoreson","sequence":"additional","affiliation":[{"name":"Urology Clinics of North Texas","place":["Dallas, Texas, United States of America"],"department":["Department of Clinical Research"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiarash","family":"Michel","sequence":"additional","affiliation":[{"name":"Comprehensive Urology","place":["Los Angeles, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jed","family":"Kaminetsky","sequence":"additional","affiliation":[{"name":"Integrated Medical Professionals","place":["New York, New York, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Belkoff","sequence":"additional","affiliation":[{"name":"MidLantic Urology","place":["Bala Cynwyd, Pennsylvania, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Huang","sequence":"additional","affiliation":[{"name":"Fellow Health Inc.","place":["San Leandro, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailey","family":"Griscom","sequence":"additional","affiliation":[{"name":"Fellow Health Inc.","place":["San Leandro, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Hart","sequence":"additional","affiliation":[{"name":"Fellow Health Inc.","place":["San Leandro, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shellie","family":"Bench","sequence":"additional","affiliation":[{"name":"Fellow Health Inc.","place":["San Leandro, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamisha","family":"Ardalani","sequence":"additional","affiliation":[{"name":"Fellow Health Inc.","place":["San Leandro, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rivas-Yepes","sequence":"additional","affiliation":[{"name":"Fellow Health Inc.","place":["San Leandro, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Civello","sequence":"additional","affiliation":[{"name":"Fellow Health Inc.","place":["San Leandro, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7525-7403","authenticated-orcid":true,"given":"Kim M.","family":"Clark-Langone","sequence":"additional","affiliation":[{"name":"Fellow Health Inc.","place":["San Leandro, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"pone.0356387.ref001","year":"2024"},{"issue":"9959","key":"pone.0356387.ref002","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1016\/S0140-6736(14)60525-0","article-title":"Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up","volume":"384","author":"FH Schr\u00f6der","year":"2014","journal-title":"Lancet"},{"issue":"2","key":"pone.0356387.ref003","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1093\/jnci\/djr500","article-title":"Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up","volume":"104","author":"GL Andriole","year":"2012","journal-title":"J Natl Cancer Inst"},{"issue":"6","key":"pone.0356387.ref004","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.eururo.2013.05.049","article-title":"Systematic review of complications of prostate biopsy","volume":"64","author":"S Loeb","year":"2013","journal-title":"Eur Urol"},{"key":"pone.0356387.ref005","first-page":"83","article-title":"Emerging biomarkers in the diagnosis of prostate cancer","volume":"11","author":"X Filella","year":"2018","journal-title":"Pharmgenomics Pers Med"},{"issue":"3","key":"pone.0356387.ref006","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/s41391-022-00537-2","article-title":"The promising role of new molecular biomarkers in prostate cancer: from coding and non-coding genes to artificial intelligence approaches","volume":"25","author":"AP Alarc\u00f3n-Zendejas","year":"2022","journal-title":"Prostate Cancer Prostatic Dis"},{"issue":"4","key":"pone.0356387.ref007","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1111\/j.1365-2125.2006.02791.x","article-title":"A new method to estimate quantitatively seminal vesicle and prostate gland contributions to ejaculate","volume":"63","author":"TT Ndovi","year":"2007","journal-title":"Br J Clin Pharmacol"},{"issue":"1","key":"pone.0356387.ref008","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s11010-021-04273-4","article-title":"Semen as a rich source of diagnostic biomarkers for prostate cancer: latest evidence and implications","volume":"477","author":"C Mao","year":"2022","journal-title":"Mol Cell Biochem"},{"key":"pone.0356387.ref009","doi-asserted-by":"crossref","DOI":"10.1016\/j.juro.2018.02.430","article-title":"PD06-10 liquid biopsy by prostate-derived tumor cells enriched from seminal fluid (sf): the semen prostate cancer tumor elements (spectre) project","volume":"199","author":"M Lazzeri","year":"2018","journal-title":"J Urol"},{"issue":"3","key":"pone.0356387.ref010","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0317712","article-title":"Tissue of origin characterization of cell free DNA in seminal plasma: implications for new liquid biopsies","volume":"20","author":"S Huang","year":"2025","journal-title":"PLoS One"},{"issue":"4","key":"pone.0356387.ref011","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s12253-018-0416-6","article-title":"Seminal cell-free DNA assessment as a novel prostate cancer biomarker","volume":"24","author":"G Ponti","year":"2018","journal-title":"Pathol Oncol Res"},{"key":"pone.0356387.ref012","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.cca.2019.07.011","article-title":"Quick assessment of cell-free DNA in seminal fluid and fragment size for early non-invasive prostate cancer diagnosis","volume":"497","author":"G Ponti","year":"2019","journal-title":"Clin Chim Acta"},{"key":"pone.0356387.ref013","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.3389\/fgene.2019.01150","article-title":"DNA methylation cancer biomarkers: translation to the clinic","volume":"10","author":"WJ Locke","year":"2019","journal-title":"Front Genet"},{"issue":"1","key":"pone.0356387.ref014","doi-asserted-by":"crossref","first-page":"5566","DOI":"10.1038\/s41467-022-32995-6","article-title":"Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer","volume":"13","author":"ML Stackpole","year":"2022","journal-title":"Nat Commun"},{"issue":"1","key":"pone.0356387.ref015","doi-asserted-by":"crossref","DOI":"10.1093\/biomethods\/bpae028","article-title":"Early detection and diagnosis of cancer with interpretable machine learning to uncover cancer-specific DNA methylation patterns","volume":"9","author":"I Newsham","year":"2024","journal-title":"Biol Methods Protoc"},{"key":"pone.0356387.ref016","unstructured":"Zhou X, Cheng Z, Dong M, Qi L, Yang W, Liu M. DNA methylation for cancer early diagnosis."},{"issue":"2","key":"pone.0356387.ref017","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2217\/epi.09.33","article-title":"DNA hypomethylation in cancer cells","volume":"1","author":"M Ehrlich","year":"2009","journal-title":"Epigenomics"},{"issue":"15","key":"pone.0356387.ref018","article-title":"CancerDetector: ultrasensitive and non-invasive cancer detection at the resolution of individual reads using cell-free DNA methylation sequencing data","volume":"46","author":"W Li","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"pone.0356387.ref019","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.annonc.2020.02.011","article-title":"Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA","volume":"31","author":"CCGA Consortium","year":"2020","journal-title":"Ann Oncol"},{"issue":"9","key":"pone.0356387.ref020","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.annonc.2021.05.806","article-title":"Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set","volume":"32","author":"EA Klein","year":"2021","journal-title":"Ann Oncol"},{"key":"pone.0356387.ref021","article-title":"Fast and accurate alignment of long bisulfite-seq reads","author":"BS Pedersen","year":"2014","journal-title":"arXiv"},{"issue":"14","key":"pone.0356387.ref022","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"issue":"2","key":"pone.0356387.ref023","doi-asserted-by":"crossref","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"P Danecek","year":"2021","journal-title":"Gigascience"},{"issue":"10","key":"pone.0356387.ref024","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2012-13-10-r87","article-title":"methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles","volume":"13","author":"A Akalin","year":"2012","journal-title":"Genome Biol"},{"issue":"3","key":"pone.0356387.ref025","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1093\/biostatistics\/kxy007","article-title":"Detection and accurate false discovery rate control of differentially methylated regions from whole genome bisulfite sequencing","volume":"20","author":"K Korthauer","year":"2019","journal-title":"Biostatistics"},{"key":"pone.0356387.ref026","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/978-3-319-24277-4_9","article-title":"Data analysis.","author":"H Wickham","year":"2016","journal-title":"ggplot2"},{"key":"pone.0356387.ref027","doi-asserted-by":"crossref","DOI":"10.18637\/jss.v028.i05","article-title":"Building predictive models in R using the caret package","volume":"28","author":"M Kuhn","year":"2008","journal-title":"J Stat Softw"},{"issue":"3","key":"pone.0356387.ref028","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1177\/2050640619828185","article-title":"The compliance rate for the second diagnostic evaluation after a positive fecal occult blood test: a systematic review and meta-analysis","volume":"7","author":"R Gingold-Belfer","year":"2019","journal-title":"United European Gastroenterol J"},{"issue":"6","key":"pone.0356387.ref029","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1097\/AOG.0000000000005723","article-title":"Compliance rate with triage test and treatment for participants screening positive in cervical cancer screening programs: a systematic review and meta-analysis","volume":"144","author":"M Wang","year":"2024","journal-title":"Obstet Gynecol"},{"issue":"10","key":"pone.0356387.ref030","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1158\/2159-8290.CD-21-1252","article-title":"The origin of highly elevated cell-free DNA in healthy individuals and patients with pancreatic, colorectal, lung, or ovarian cancer","volume":"13","author":"AK Mattox","year":"2023","journal-title":"Cancer Discov"},{"key":"pone.0356387.ref031","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1093\/clinchem\/hvac122","article-title":"Urinary cell-free DNA in liquid biopsy and cancer management","volume":"68","author":"B Salfer","year":"2022","journal-title":"Clin Chem"},{"issue":"6","key":"pone.0356387.ref032","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.ajhg.2024.04.017","article-title":"Genome-wide DNA methylation changes in human spermatogenesis","volume":"111","author":"LM Siebert-Kuss","year":"2024","journal-title":"Am J Hum Genet"},{"key":"pone.0356387.ref033","doi-asserted-by":"crossref","first-page":"6372171","DOI":"10.1155\/2016\/6372171","article-title":"Different levels of DNA methylation detected in human sperms after morphological selection using high magnification microscopy","volume":"2016","author":"NG Cassuto","year":"2016","journal-title":"Biomed Res Int"},{"issue":"1","key":"pone.0356387.ref034","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13072-023-00508-4","article-title":"Altered cfDNA fragmentation profile in hypomethylated regions as diagnostic markers in breast cancer","volume":"16","author":"J Wang","year":"2023","journal-title":"Epigenetics Chromatin"},{"issue":"1","key":"pone.0356387.ref035","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41467-023-35959-6","article-title":"DNA methylation analysis explores the molecular basis of plasma cell-free DNA fragmentation","volume":"14","author":"Y An","year":"2023","journal-title":"Nat Commun"},{"issue":"2","key":"pone.0356387.ref036","first-page":"106","article-title":"Exogenous testosterone: a preventable cause of male infertility","volume":"2","author":"LE Crosnoe","year":"2013","journal-title":"Transl Androl Urol"},{"issue":"1","key":"pone.0356387.ref037","doi-asserted-by":"crossref","first-page":"45","DOI":"10.5534\/wjmh.180036","article-title":"Testosterone is a contraceptive and should not be used in men who desire fertility","volume":"37","author":"AS Patel","year":"2019","journal-title":"World J Mens Health"},{"key":"pone.0356387.ref038","article-title":"epiCaPture: A urine DNA methylation test for early detection of aggressive prostate cancer","volume":"2019","author":"E O\u2019Reilly","year":"2019","journal-title":"JCO Precis Oncol"},{"key":"pone.0356387.ref039","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jsbmb.2016.04.009","article-title":"The importance of DNA methylation in prostate cancer development","volume":"166","author":"CE Massie","year":"2017","journal-title":"J Steroid Biochem Mol Biol"},{"key":"pone.0356387.ref040","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s13148-018-0524-x","article-title":"A panel of DNA methylation markers for the detection of prostate cancer from FV and DRE urine DNA","volume":"10","author":"I Brikun","year":"2018","journal-title":"Clin Epigenetics"},{"issue":"5","key":"pone.0356387.ref041","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1016\/j.juro.2011.06.052","article-title":"Predicting prostate biopsy result in men with prostate specific antigen 2.0 to 10.0 ng\/ml using an investigational prostate cancer methylation assay","volume":"186","author":"J Baden","year":"2011","journal-title":"J Urol"},{"issue":"18","key":"pone.0356387.ref042","doi-asserted-by":"crossref","first-page":"6582","DOI":"10.1158\/1078-0432.CCR-05-0658","article-title":"Multigene methylation analysis for detection and staging of prostate cancer","volume":"11","author":"H Enokida","year":"2005","journal-title":"Clin Cancer Res"},{"issue":"1","key":"pone.0356387.ref043","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jmoldx.2019.08.003","article-title":"Methylation markers in prostate biopsies are prognosticators for late biochemical recurrence and therapy after surgery in prostate cancer patients","volume":"22","author":"AJ Savio","year":"2020","journal-title":"J Mol Diagn"},{"issue":"1","key":"pone.0356387.ref044","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s13148-019-0716-z","article-title":"Urinary DNA methylation biomarkers for prediction of prostate cancer upgrading and upstaging","volume":"11","author":"A Bakavicius","year":"2019","journal-title":"Clin Epigenetics"},{"issue":"9","key":"pone.0356387.ref045","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1038\/s41416-018-0236-1","article-title":"Phenotype-independent DNA methylation changes in prostate cancer","volume":"119","author":"D Pellacani","year":"2018","journal-title":"Br J Cancer"},{"issue":"15","key":"pone.0356387.ref046","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.2217\/epi-2020-0173","article-title":"Dynamics of the cell-free DNA methylome of metastatic prostate cancer during androgen-targeting treatment","volume":"12","author":"MR Peter","year":"2020","journal-title":"Epigenomics"},{"issue":"1","key":"pone.0356387.ref047","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s12967-021-02710-y","article-title":"Chromatin conformation changes in peripheral blood can detect prostate cancer and stratify disease risk groups","volume":"19","author":"H Alshaker","year":"2021","journal-title":"J Transl Med"},{"issue":"1","key":"pone.0356387.ref048","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s13148-019-0736-8","article-title":"Random forest-based modelling to detect biomarkers for prostate cancer progression","volume":"11","author":"R Toth","year":"2019","journal-title":"Clin Epigenetics"},{"issue":"10","key":"pone.0356387.ref049","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.3390\/cancers12102993","article-title":"Advances in prognostic methylation biomarkers for prostate cancer","volume":"12","author":"D Lam","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"5","key":"pone.0356387.ref050","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1016\/j.juro.2007.01.010","article-title":"Discovery and validation of 3 novel DNA methylation markers of prostate cancer prognosis","volume":"177","author":"S Cottrell","year":"2007","journal-title":"J Urol"},{"issue":"4","key":"pone.0356387.ref051","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1593\/neo.122146","article-title":"Epigenomic alterations in localized and advanced prostate cancer","volume":"15","author":"P-C Lin","year":"2013","journal-title":"Neoplasia"},{"issue":"10","key":"pone.0356387.ref052","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1016\/j.celrep.2015.10.078","article-title":"Methylome-wide sequencing detects DNA hypermethylation distinguishing indolent from aggressive prostate cancer","volume":"13","author":"JM Bhasin","year":"2015","journal-title":"Cell Rep"},{"issue":"1","key":"pone.0356387.ref053","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1186\/s12885-017-3252-2","article-title":"Genome-wide DNA methylation measurements in prostate tissues uncovers novel prostate cancer diagnostic biomarkers and transcription factor binding patterns","volume":"17","author":"MK Kirby","year":"2017","journal-title":"BMC Cancer"},{"key":"pone.0356387.ref054","doi-asserted-by":"crossref","first-page":"654140","DOI":"10.3389\/fonc.2021.654140","article-title":"Post-biopsy cell-free DNA from blood: an open window on primary prostate cancer genetics and biology","volume":"11","author":"M Corbetta","year":"2021","journal-title":"Front Oncol"},{"issue":"10","key":"pone.0356387.ref055","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.3390\/cancers15102666","article-title":"Evaluation of semen self-sampling yield predictors and CTC isolation by multi-color flow cytometry for liquid biopsy of localized prostate cancer","volume":"15","author":"C Saitta","year":"2023","journal-title":"Cancers (Basel)"},{"issue":"4804","key":"pone.0356387.ref056","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1126\/science.3576213","article-title":"Sequence-specific packaging of DNA in human sperm chromatin","volume":"236","author":"JM Gatewood","year":"1987","journal-title":"Science"},{"issue":"9","key":"pone.0356387.ref057","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1186\/gb-2007-8-9-227","article-title":"The protamine family of sperm nuclear proteins","volume":"8","author":"R Balhorn","year":"2007","journal-title":"Genome Biol"},{"key":"pone.0356387.ref058","first-page":"28","article-title":"Targeting NETosis: nature\u2019s alarm system in cancer progression","volume":"7","author":"Y Liang","year":"2024","journal-title":"Cancer Drug Resist"},{"issue":"21","key":"pone.0356387.ref059","doi-asserted-by":"crossref","first-page":"15805","DOI":"10.3390\/ijms242115805","article-title":"Role of neutrophil extracellular traps in health and disease pathophysiology: recent insights and advances","volume":"24","author":"MM Islam","year":"2023","journal-title":"Int J Mol Sci"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0356387","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:33:31Z","timestamp":1788975211000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0356387"}},"subtitle":[],"editor":[{"given":"Elingarami","family":"Sauli","sequence":"first","affiliation":[{"name":"Nelson Mandela African Institute of Science and Technology","place":["TANZANIA, UNITED REPUBLIC OF"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":59,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0356387","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]}}}