title: Microarray-based cell-free DNA analysis improves noninvasive prenatal testing.
abstract: OBJECTIVE
  To develop a microarray-based method for noninvasive prenatal testing (NIPT) and compare it with next-generation sequencing.
  
  
  METHODS
  Maternal plasma from 878 pregnant women, including 187 trisomy cases (18 trisomy 13, 37 trisomy 18, 132 trisomy 21), was evaluated for trisomy risk. Targeted chromosomes were analyzed using Digital Analysis of Selected Regions (DANSR™) assays. DANSR products were subsequently divided between two DNA quantification methods: microarrays and next-generation sequencing. For both microarray and sequencing methodologies, the Fetal-Fraction Optimized Risk of Trisomy Evaluation (FORTE™) algorithm was used to determine trisomy risk, assay variability across samples, and compute fetal fraction variability within samples.
  
  
  RESULTS
  NIPT using microarrays provided faster and more accurate cell-free DNA (cfDNA) measurements than sequencing. The assay variability, a measure of variance of chromosomal cfDNA counts, was lower for microarrays than for sequencing, 0.051 versus 0.099 (p < 0.0001). Analysis time using microarrays was faster, 7.5 versus 56 h for sequencing. Additionally, fetal fraction precision was improved 1.6-fold by assaying more polymorphic sites with microarrays (p < 0.0001). Microarrays correctly classified all trisomy and nontrisomy cases.
  
  
  CONCLUSIONS
  NIPT using microarrays delivers more accurate cfDNA analysis than next-generation sequencing and can be performed in less time.
authors.affiliation: Ariosa Diagnostics Inc., San Jose, Calif., USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Juneau
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Bogard
authors.forename: Stephanie
authors.initials: S
authors.lastname: Huang
authors.forename: Morassa
authors.initials: M
authors.lastname: Mohseni
authors.forename: Eric T
authors.initials: ET
authors.lastname: Wang
authors.forename: Paul
authors.initials: P
authors.lastname: Ryvkin
authors.forename: Christopher
authors.initials: C
authors.lastname: Kingsley
authors.forename: Craig A
authors.initials: CA
authors.lastname: Struble
authors.forename: Arnold
authors.initials: A
authors.lastname: Oliphant
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Zahn
mesh_terms: D000328:Adult; D000782:Aneuploidy; D004247:DNA / Q000097:blood; D005260:Female; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D017422:Sequence Analysis, DNA; D014314:Trisomy / Q000175:diagnosis* / Q000235:genetics
chemical_list: D004247:DNA