title: Proteomic profile determination of autosomal aneuploidies by mass spectrometry on amniotic fluids.
abstract: BACKGROUND
  Prenatal diagnosis of chromosomal abnormalities by cytogenetic analysis is time-consuming, expensive, and requires highly qualified technicians. Rapid diagnosis of aneuploidies followed by reassurance of women with normal results can be performed by molecular analysis of uncultured foetal cells. In the present study, we developed a proteomic fingerprinting approach coupled with a statistical classification method to improve diagnosis of aneuploidies, including trisomies 13, 18, and 21, in amniotic fluid samples.
  
  
  RESULTS
  The proteomic spectra obtained from 52 pregnant women were compiled, normalized, and mass peaks with mass-to-charge ratios between 2.5 and 50 kDa identified. Peak information was combined together and analysed using univariate statistics. Among the 208 expressed protein peaks, 40 differed significantly between aneuploid and non aneuploid samples, with AUC diagnostic values ranging from 0.71 to 0.91. Hierarchical clustering, principal component analysis and support vector machine (SVM) analysis were performed. Two class predictor models were defined from the training set, which resulted in a prediction accuracy of 92.3% and 96.43%, respectively. Using an external and independent validation set, diagnostic accuracies were maintained at 87.5% and 91.67%, respectively.
  
  
  CONCLUSIONS
  This pilot study demonstrates the potential interest of protein expression signature in the identification of new potential biological markers that might be helpful for the rapid clinical management of high-risk pregnancies.
authors.affiliation: University of Montpellier I, France. alain.mange@univ-montp1.fr
authors.forename: Alain
authors.initials: A
authors.lastname: Mange
authors.forename: Caroline
authors.initials: C
authors.lastname: Desmetz
authors.forename: Virginie
authors.initials: V
authors.lastname: Bellet
authors.forename: Nicolas
authors.initials: N
authors.lastname: Molinari
authors.forename: Thierry
authors.initials: T
authors.lastname: Maudelonde
authors.forename: Jerome
authors.initials: J
authors.lastname: Solassol