title: Open source non-invasive prenatal testing platform and its performance in a public health laboratory.
abstract: OBJECTIVE
  The objective of this study was to introduce non-invasive prenatal testing (NIPT) for fetal autosomal trisomies and gender in a Danish public health setting, using semi-conductor sequencing and published open source scripts for analysis.
  
  
  METHODS
  Plasma-derived DNA from a total of 375 pregnant women (divided into three datasets) was whole-genome sequenced on the Ion Proton™ platform and analyzed using a pipeline based on WISECONDOR for fetal autosomal aneuploidy detection and SeqFF for fetal DNA fraction estimation. We furthermore validated a fetal sex determination analysis.
  
  
  RESULTS
  The pipeline correctly detected 27/27 trisomy 21, 4/4 trisomy 18, and 3/3 trisomy 13 fetuses. Neither false negatives nor false positives (chromosomes 13, 18, and 21) were observed in our validation dataset. Fetal sex was identified correctly in all but one triploid fetus (172/173). SeqFF showed a strong correlation (R(2)  = 0.72) to Y-chromosomal content of the male fetus samples.
  
  
  CONCLUSIONS
  We have implemented NIPT into Danish health care using published open source scripts for autosomal aneuploidy detection and fetal DNA fraction estimation showing excellent false negative and false positive rates. SeqFF provides a good estimation of fetal DNA fraction. This coupled with an analysis of fetal sex that provides a complete NIPT workflow, which may easily be adapted for implementation in other public health laboratories. © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Chromosome Laboratory, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Peter
authors.identifier: http://orcid.org/0000-0001-9963-8941
authors.initials: P
authors.lastname: Johansen
authors.affiliation: Chromosome Laboratory, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Stine R
authors.initials: SR
authors.lastname: Richter
authors.affiliation: Chromosome Laboratory, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Marie
authors.initials: M
authors.lastname: Balslev-Harder
authors.affiliation: Center of Fetal Medicine and Pregnancy, Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Caroline B
authors.initials: CB
authors.lastname: Miltoft
authors.affiliation: Center of Fetal Medicine and Pregnancy, Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Ann
authors.initials: A
authors.lastname: Tabor
authors.affiliation: Molecular Genetics Laboratory, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Duno
authors.affiliation: Chromosome Laboratory, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kjaergaard
mesh_terms: D000328:Adult; D025063:Chromosome Disorders / Q000175:diagnosis*; D002882:Chromosomes, Human, Pair 13; D002887:Chromosomes, Human, Pair 18; D004247:DNA / Q000097:blood* / Q000235:genetics; D003718:Denmark; D004314:Down Syndrome / Q000175:diagnosis*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D008297:Male; D062145:Maternal Serum Screening Tests / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011634:Public Health; D012666:Semiconductors; D017422:Sequence Analysis, DNA / Q000295:instrumentation / Q000379:methods*; D012732:Sex Determination Analysis; D014314:Trisomy / Q000175:diagnosis*; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome
chemical_list: D004247:DNA