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Proteomic profile determination of autosomal aneuploidies by mass spectrometry on amniotic fluids

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 foeta...

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Autores principales: Mange, Alain, Desmetz, Caroline, Bellet, Virginie, Molinari, Nicolas, Maudelonde, Thierry, Solassol, Jerome
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2248173/
https://www.ncbi.nlm.nih.gov/pubmed/18190690
http://dx.doi.org/10.1186/1477-5956-6-1
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author Mange, Alain
Desmetz, Caroline
Bellet, Virginie
Molinari, Nicolas
Maudelonde, Thierry
Solassol, Jerome
author_facet Mange, Alain
Desmetz, Caroline
Bellet, Virginie
Molinari, Nicolas
Maudelonde, Thierry
Solassol, Jerome
author_sort Mange, Alain
collection PubMed
description 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. CONCLUSION: 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.
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spelling pubmed-22481732008-02-20 Proteomic profile determination of autosomal aneuploidies by mass spectrometry on amniotic fluids Mange, Alain Desmetz, Caroline Bellet, Virginie Molinari, Nicolas Maudelonde, Thierry Solassol, Jerome Proteome Sci Research 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. CONCLUSION: 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. BioMed Central 2008-01-11 /pmc/articles/PMC2248173/ /pubmed/18190690 http://dx.doi.org/10.1186/1477-5956-6-1 Text en Copyright © 2008 Mange et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Mange, Alain
Desmetz, Caroline
Bellet, Virginie
Molinari, Nicolas
Maudelonde, Thierry
Solassol, Jerome
Proteomic profile determination of autosomal aneuploidies by mass spectrometry on amniotic fluids
title Proteomic profile determination of autosomal aneuploidies by mass spectrometry on amniotic fluids
title_full Proteomic profile determination of autosomal aneuploidies by mass spectrometry on amniotic fluids
title_fullStr Proteomic profile determination of autosomal aneuploidies by mass spectrometry on amniotic fluids
title_full_unstemmed Proteomic profile determination of autosomal aneuploidies by mass spectrometry on amniotic fluids
title_short Proteomic profile determination of autosomal aneuploidies by mass spectrometry on amniotic fluids
title_sort proteomic profile determination of autosomal aneuploidies by mass spectrometry on amniotic fluids
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2248173/
https://www.ncbi.nlm.nih.gov/pubmed/18190690
http://dx.doi.org/10.1186/1477-5956-6-1
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