title: The feasibility study of non-invasive fetal trisomy 18 and 21 detection with semiconductor sequencing platform.
abstract: OBJECTIVE
  Recent non-invasive prenatal testing (NIPT) technologies are based on next-generation sequencing (NGS). NGS allows rapid and effective clinical diagnoses to be determined with two common sequencing systems: Illumina and Ion Torrent platforms. The majority of NIPT technology is associated with Illumina platform. We investigated whether fetal trisomy 18 and 21 were sensitively and specifically detectable by semiconductor sequencer: Ion Proton.
  
  
  METHODS
  From March 2012 to October 2013, we enrolled 155 pregnant women with fetuses who were diagnosed as high risk of fetal defects at Xiamen Maternal & Child Health Care Hospital (Xiamen, Fujian, China). Adapter-ligated DNA libraries were analyzed by the Ion Proton™ System (Life Technologies, Grand Island, NY, USA) with an average 0.3× sequencing coverage per nucleotide. Average total raw reads per sample was 6.5 million and mean rate of uniquely mapped reads was 59.0%. The results of this study were derived from BWA mapping. Z-score was used for fetal trisomy 18 and 21 detection.
  
  
  RESULTS
  Interactive dot diagrams showed the minimal z-score values to discriminate negative versus positive cases of fetal trisomy 18 and 21. For fetal trisomy 18, the minimal z-score value of 2.459 showed 100% positive predictive and negative predictive values. The minimal z-score of 2.566 was used to classify negative versus positive cases of fetal trisomy 21.
  
  
  CONCLUSIONS
  These results provide the evidence that fetal trisomy 18 and 21 detection can be performed with semiconductor sequencer. Our data also suggest that a prospective study should be performed with a larger cohort of clinically diverse obstetrics patients.
authors.affiliation: TheragenEtex Bio Institute, Suwon, Republic of Korea; Genome Care, Seoul, South Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Jeon
authors.affiliation: Molecular Diagnostics Laboratory, Department of Medical Genetics, Prenatal Diagnosis Center, Xiamen Maternal and Child Health Hospital, Xiamen, Fujian, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Xiamen Hospital of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Xiamen, Fujian, China.
authors.forename: Yihan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Molecular Diagnostics Laboratory, Department of Medical Genetics, Prenatal Diagnosis Center, Xiamen Maternal and Child Health Hospital, Xiamen, Fujian, China.
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Xiamen Hospital of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Xiamen, Fujian, China.
authors.forename: Jinchun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Xiamen Vangenes BioTech, Xiamen, Fujian, China.
authors.forename: Shengmao
authors.initials: S
authors.lastname: Quan
authors.affiliation: Xiamen Vangenes BioTech, Xiamen, Fujian, China.
authors.forename: Ahong
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Xiamen Vangenes BioTech, Xiamen, Fujian, China.
authors.forename: Hailing
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Xiamen Vangenes BioTech, Xiamen, Fujian, China.
authors.forename: Xingqiang
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Xiamen Vangenes BioTech, Xiamen, Fujian, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Lin
authors.affiliation: Xiamen Vangenes BioTech, Xiamen, Fujian, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Xu
authors.affiliation: Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China.
authors.forename: Ayang
authors.initials: A
authors.lastname: Wu
authors.affiliation: TheragenEtex Bio Institute, Suwon, Republic of Korea; Genome Care, Seoul, South Korea.
authors.forename: Sin-Gi
authors.initials: SG
authors.lastname: Park
authors.affiliation: Clinomics, Ulsan, Republic of Korea; Personal Genomics Institute, Genome Research Foundation, Suwon, Republic of Korea.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Kim
authors.affiliation: TheragenEtex Bio Institute, Suwon, Republic of Korea; Genome Care, Seoul, South Korea.
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Joo
authors.affiliation: Xiamen Vangenes BioTech, Xiamen, Fujian, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Chen
authors.affiliation: TheragenEtex Bio Institute, Suwon, Republic of Korea; Genome Care, Seoul, South Korea; Personal Genomics Institute, Genome Research Foundation, Suwon, Republic of Korea; BioMedical Engineering, UNIST, Ulsan, Republic of Korea.
authors.forename: Jong
authors.initials: J
authors.lastname: Bhak
mesh_terms: D000328:Adult; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D004314:Down Syndrome / Q000175:diagnosis* / Q000235:genetics; D005240:Feasibility Studies; D005260:Female; D005333:Fetus; D059014:High-Throughput Nucleotide Sequencing / Q000295:instrumentation*; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000295:instrumentation*; D012666:Semiconductors; D017422:Sequence Analysis, DNA / Q000295:instrumentation*; D014314:Trisomy / Q000175:diagnosis* / Q000235:genetics; D000073842:Trisomy 18 Syndrome; D055815:Young Adult