{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:34:52Z","timestamp":1793381692814,"version":"4.5.0"},"reference-count":15,"publisher":"CERN","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Commission","award":["874719"],"award-info":[{"award-number":["874719"]}],"id":[{"id":"https:\/\/ror.org\/00k4n6c32","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Federal Ministry of Education, Science and Research","award":["FKZ01KD2103A"],"award-info":[{"award-number":["FKZ01KD2103A"]}],"id":[{"id":"https:\/\/ror.org\/03gng8t46","id-type":"ROR","asserted-by":"publisher"}]},{"name":"German Research Foundation","award":["444949889"],"award-info":[{"award-number":["444949889"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]},{"name":"German Research Foundation","award":["525136051"],"award-info":[{"award-number":["525136051"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Open Res Europe"],"abstract":"<jats:p>Background\n                    Pancreatic cancer and ovarian cancer are very challenging to diagnose at early stages. The endoscopic retrieval of biopsy tissue from a suspected benign or malignant lesion is challenging due to the tissue\u2019s nature. Therefore, within the Instand-NGS4P framework, we developed Measurable Residual Disease (MRD) prototypes to analyze blood plasma samples, with the aim of cost-effectively supporting the differential diagnosis of suspected pancreatic or ovarian neoplasms.\n                \n                \n                    Methods\n                    Our MRD prototypes examine blood plasma for mutations in cell-free DNA in specific genes associated with pancreatic neoplasms or ovarian neoplasms, respectively. Unique molecular identifiers (UMIs) are used to enable bioinformatic error correction. Ultra-deep sequencing is demonstrated on sequencing platforms from two different vendors (Illumina and MGI). We provide detailed information on bioinformatic processing of sequencing data to perform error-correction.\n                \n                \n                    Results\n                    Using commercially available reference standards, we demonstrate stable mutation detection down to a variant allele frequency (VAF) of 0.1%. At a coverage of 4,000x duplex consensus reads, only two false positives were observed, which can be efficiently mitigated using an appropriate filtering strategy.\n                \n                \n                    Conclusions\n                    The technical usability of our MRD prototype has been clearly demonstrated for stable low-level VAF detection in commercial reference samples.<\/jats:p>","DOI":"10.12688\/openreseurope.23403.1","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T12:44:09Z","timestamp":1775220249000},"update-policy":"https:\/\/doi.org\/10.68336\/openreseurope.updatepolicy","source":"Crossref","is-referenced-by-count":0,"title":["Method development for pancreatic and ovarian cancer baseline ctDNA detection and measurable residual disease monitoring"],"prefix":"10.68336","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0125-1173","authenticated-orcid":true,"given":"Tim Alexander","family":"Steiert","sequence":"first","affiliation":[{"name":"Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel & University Hospital Schleswig-Holstein, Kiel, Schleswig-Holstein, 24118, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp M.","family":"Altrock","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Christian-Albrechts-University of Kiel & University Hospital Schleswig-Holstein, Kiel, Schleswig-Holstein, 24105, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"K\u00fcnstner","sequence":"additional","affiliation":[{"name":"Medical Systems Biology Group, L\u00fcbeck Institute of Experimental Dermatology, University of L\u00fcbeck, L\u00fcbeck, Schleswig-Holstein, 23538, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Dixit","sequence":"additional","affiliation":[{"name":"Twist Bioscience, Inc., South San Francisco, California, 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Brandt","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein, Kiel, Schleswig-Holstein, 24105, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4017-3574","authenticated-orcid":true,"given":"Pamela","family":"Pinzani","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences, University of Florence and Molecular and Clinical Biochemistry Unit, Careggi University Hospital, Florence, Tuscany, 50139, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hauke","family":"Busch","sequence":"additional","affiliation":[{"name":"Medical Systems Biology Group, L\u00fcbeck Institute of Experimental Dermatology, University of L\u00fcbeck, L\u00fcbeck, Schleswig-Holstein, 23538, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Franke","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel & University Hospital Schleswig-Holstein, Kiel, Schleswig-Holstein, 24118, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Forster","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel & University Hospital Schleswig-Holstein, Kiel, Schleswig-Holstein, 24118, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"13904","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"106453","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-03-580027"},{"key":"106454","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf6219"},{"key":"106455","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.02.007"},{"key":"106456","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aab0021"},{"key":"106457","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz048"},{"key":"106458","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.02052"},{"key":"106459","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2022.1557"},{"key":"106460","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.01220"},{"key":"106461","doi-asserted-by":"publisher","DOI":"10.1787\/20ef03e1-en"},{"key":"106462","doi-asserted-by":"publisher","DOI":"10.1186\/gm492"},{"key":"106463","doi-asserted-by":"crossref","unstructured":"11. Pengelly RJ, Gibson J, Andreoletti G, et al.: Erratum to: A SNP profiling panel for sample tracking in whole-exome sequencing studies. Genome Med. 2015; 7(5): 44.","DOI":"10.1186\/s13073-015-0163-1"},{"key":"106464","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0334282"},{"key":"106465","doi-asserted-by":"publisher","DOI":"10.1038\/s44321-024-00115-0"},{"key":"106466","unstructured":"14. Steiert TA, Altrock PM, K\u00fcnstner A, et al.: Aligned bam files: Measurable Residual Disease method development for pancreatic and ovarian cancer detection. Eur. Nucleot. Arch. 2026. Reference Source (https:\/\/www.ebi.ac.uk\/ena\/browser\/view\/PRJEB108992)"},{"key":"106467","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.18967866"}],"updated-by":[{"DOI":"10.12688\/openreseurope.23403.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000}}],"container-title":["Open Research Europe"],"original-title":[],"link":[{"URL":"https:\/\/open-research-europe.ec.europa.eu\/articles\/6-87\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ore.eu\/ore\/article\/download\/1282\/version\/2187\/4371","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ore.eu\/ore\/article\/download\/1282\/version\/2187\/4372","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ore.eu\/ore\/article\/download\/1282\/version\/2187\/4371","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:12:03Z","timestamp":1793380323000},"score":1,"resource":{"primary":{"URL":"https:\/\/ore.eu\/ore\/article\/view\/1282\/version\/2187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,3]]},"references-count":15,"URL":"https:\/\/doi.org\/10.12688\/openreseurope.23403.1","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/openreseurope.23403.2","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.21956\/openreseurope.25321.r72658","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/openreseurope.25321.r72154","asserted-by":"object"}]},"ISSN":["2732-5121"],"issn-type":[{"value":"2732-5121","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,3]]},"assertion":[{"value":"2026-04-03","name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}},{"value":"This project has received funding from the European Union\u2019s Horizon 2020 research and innovation programme under grant agreement No 874719 supported by Instand-NGS4P \u201cINtegrated and Standardized NGS workflows FOR Personalized therapy. H.B. and A.K. acknowledge support from the Bundesministerium f\u00fcr Bildung und Forschung project Outlive Colorectal Cancer Consortium (FKZ 01KD2103A). P.M.A acknowledges funding by the DFG (German Research Foundation) through the Clinical Research Unit KFO 5010 CATCH ALL (project number 444949889) and the Heisenberg Program (project number 525136051). \n\n                    The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","name":"funding_statement","label":"Funding Statement","group":{"name":"funding_information","label":"Funding Information"}}],"article-number":"87"}}