{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:17:57Z","timestamp":1772173077792,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009684","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T00:00:00Z","timestamp":1641168000000}}],"reference-count":21,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006598","name":"Ettev\u00f5tluse Arendamise Sihtasutus","doi-asserted-by":"publisher","award":["EU48695"],"award-info":[{"award-number":["EU48695"]}],"id":[{"id":"10.13039\/501100006598","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006598","name":"Ettev\u00f5tluse Arendamise Sihtasutus","doi-asserted-by":"publisher","award":["EU53935"],"award-info":[{"award-number":["EU53935"]}],"id":[{"id":"10.13039\/501100006598","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006598","name":"Ettev\u00f5tluse Arendamise Sihtasutus","doi-asserted-by":"publisher","award":["EU53935"],"award-info":[{"award-number":["EU53935"]}],"id":[{"id":"10.13039\/501100006598","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002301","name":"Eesti Teadusagentuur","doi-asserted-by":"publisher","award":["PRG1076"],"award-info":[{"award-number":["PRG1076"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["EU952516"],"award-info":[{"award-number":["EU952516"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Non-invasive prenatal testing (NIPT) is a powerful screening method for fetal aneuploidy detection, relying on laboratory and computational analysis of cell-free DNA. Although several published computational NIPT analysis tools are available, no prior comprehensive, head-to-head accuracy comparison of the various tools has been published. Here, we compared the outcome accuracies obtained for clinically validated samples with five commonly used computational NIPT aneuploidy analysis tools (WisecondorX, NIPTeR, NIPTmer, RAPIDR, and GIPseq) across various sequencing depths (coverage) and fetal DNA fractions. The sample set included cases of fetal trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome). We determined that all of the compared tools were considerably affected by lower sequencing depths, such that increasing proportions of undetected trisomy cases (false negatives) were observed as the sequencing depth decreased. We summarised our benchmarking results and highlighted the advantages and disadvantages of each computational NIPT software. To conclude, trisomy detection for lower coverage NIPT samples (e.g. 2.5M reads per sample) is technically possible but can, with some NIPT tools, produce troubling rates of inaccurate trisomy detection, especially in low-FF samples.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009684","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T14:05:36Z","timestamp":1640009136000},"page":"e1009684","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Systematic evaluation of NIPT aneuploidy detection software tools with clinically validated NIPT samples"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2016-661X","authenticated-orcid":true,"given":"Priit","family":"Paluoja","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6608-7979","authenticated-orcid":true,"given":"Hindrek","family":"Teder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7226-7324","authenticated-orcid":true,"given":"Amin","family":"Ardeshirdavani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baran","family":"Bayindir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3071-1191","authenticated-orcid":true,"given":"Joris","family":"Vermeesch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-8160","authenticated-orcid":true,"given":"Andres","family":"Salumets","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1297-1464","authenticated-orcid":true,"given":"Kaarel","family":"Krjut\u0161kov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9320-7008","authenticated-orcid":true,"given":"Priit","family":"Palta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"pcbi.1009684.ref001","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.3109\/14767058.2012.678442","article-title":"Clinical utility of noninvasive fetal trisomy (NIFTY) test early experience","volume":"25","author":"TK Lau","year":"2012","journal-title":"J Matern Neonatal Med"},{"key":"pcbi.1009684.ref002","doi-asserted-by":"crossref","first-page":"e0209139","DOI":"10.1371\/journal.pone.0209139","article-title":"Computational framework for targeted high-coverage sequencing based NIPT","volume":"14","author":"H Teder","year":"2019","journal-title":"PLoS One"},{"key":"pcbi.1009684.ref003","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1038\/ejhg.2014.282","article-title":"Noninvasive prenatal testing using a novel analysis pipeline to screen for all autosomal fetal aneuploidies improves pregnancy management","volume":"23","author":"B Bayindir","year":"2015","journal-title":"Eur J Hum Genet"},{"key":"pcbi.1009684.ref004","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2147\/IJWH.S67124","article-title":"Non-invasive prenatal testing: a review of international implementation and challenges","volume":"7","author":"M Allyse","year":"2015","journal-title":"Int J Womens Health"},{"key":"pcbi.1009684.ref005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-23589-8","article-title":"NIPTmer: Rapid k-mer-based software package for detection of fetal aneuploidies","volume":"8","author":"M Sauk","year":"2018","journal-title":"Sci Rep"},{"key":"pcbi.1009684.ref006","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1186\/s12859-018-2557-8","article-title":"NIPTeR: An R package for fast and accurate trisomy prediction in non-invasive prenatal testing","volume":"19","author":"LF Johansson","year":"2018","journal-title":"BMC Bioinformatics"},{"key":"pcbi.1009684.ref007","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.1093\/bioinformatics\/btu419","article-title":"RAPIDR: an analysis package for non-invasive prenatal testing of aneuploidy","volume":"30","author":"KK Lo","year":"2014","journal-title":"Bioinformatics"},{"key":"pcbi.1009684.ref008","first-page":"2016","article-title":"DASAF: An R Package for Deep Sequencing-Based Detection of Fetal Autosomal Abnormalities from Maternal Cell-Free DNA","author":"B Liu","year":"2016","journal-title":"Biomed Res Int"},{"key":"pcbi.1009684.ref009","author":"R Straver","journal-title":"WISECONDOR: detection of fetal aberrations from shallow sequencing maternal plasma based on a within-sample comparison scheme"},{"key":"pcbi.1009684.ref010","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1093\/nar\/gky1263","article-title":"WisecondorX: improved copy number detection for routine shallow whole-genome sequencing","volume":"47","author":"L Raman","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1009684.ref011","doi-asserted-by":"crossref","first-page":"e0238245","DOI":"10.1371\/journal.pone.0238245","article-title":"Non-invasive prenatal testing (NIPT) by low coverage genomic sequencing: Detection limits of screened chromosomal microdeletions","volume":"15","author":"M Kucharik","year":"2020","journal-title":"PLoS One"},{"key":"pcbi.1009684.ref012","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/pd.5620","article-title":"Fetal fraction and noninvasive prenatal testing: What clinicians need to know","volume":"40","author":"L Hui","year":"2020","journal-title":"Prenat Diagn"},{"key":"pcbi.1009684.ref013","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1002\/pd.4126","article-title":"The impact of maternal plasma DNA fetal fraction on next generation sequencing tests for common fetal aneuploidies","volume":"33","author":"JA Canick","year":"2013","journal-title":"Prenat Diagn"},{"key":"pcbi.1009684.ref014","first-page":"678","article-title":"Targeted fetal cell-free DNA screening for aneuploidies in 4,594 pregnancies: Single center study","volume":"7","author":"A Koc","year":"2019","journal-title":"Mol Genet Genomic 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