Cargando…

Probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (MLPA)

BACKGROUND: MLPA method is a potentially useful semi-quantitative method to detect copy number alterations in targeted regions. In this paper, we propose a method for the normalization procedure based on a non-linear mixed-model, as well as a new approach for determining the statistical significance...

Descripción completa

Detalles Bibliográficos
Autores principales: González, Juan R, Carrasco, Josep L, Armengol, Lluís, Villatoro, Sergi, Jover, Lluís, Yasui, Yutaka, Estivill, Xavier
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2492880/
https://www.ncbi.nlm.nih.gov/pubmed/18522760
http://dx.doi.org/10.1186/1471-2105-9-261
_version_ 1782158205939351552
author González, Juan R
Carrasco, Josep L
Armengol, Lluís
Villatoro, Sergi
Jover, Lluís
Yasui, Yutaka
Estivill, Xavier
author_facet González, Juan R
Carrasco, Josep L
Armengol, Lluís
Villatoro, Sergi
Jover, Lluís
Yasui, Yutaka
Estivill, Xavier
author_sort González, Juan R
collection PubMed
description BACKGROUND: MLPA method is a potentially useful semi-quantitative method to detect copy number alterations in targeted regions. In this paper, we propose a method for the normalization procedure based on a non-linear mixed-model, as well as a new approach for determining the statistical significance of altered probes based on linear mixed-model. This method establishes a threshold by using different tolerance intervals that accommodates the specific random error variability observed in each test sample. RESULTS: Through simulation studies we have shown that our proposed method outperforms two existing methods that are based on simple threshold rules or iterative regression. We have illustrated the method using a controlled MLPA assay in which targeted regions are variable in copy number in individuals suffering from different disorders such as Prader-Willi, DiGeorge or Autism showing the best performace. CONCLUSION: Using the proposed mixed-model, we are able to determine thresholds to decide whether a region is altered. These threholds are specific for each individual, incorporating experimental variability, resulting in improved sensitivity and specificity as the examples with real data have revealed.
format Text
id pubmed-2492880
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-24928802008-08-01 Probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (MLPA) González, Juan R Carrasco, Josep L Armengol, Lluís Villatoro, Sergi Jover, Lluís Yasui, Yutaka Estivill, Xavier BMC Bioinformatics Methodology Article BACKGROUND: MLPA method is a potentially useful semi-quantitative method to detect copy number alterations in targeted regions. In this paper, we propose a method for the normalization procedure based on a non-linear mixed-model, as well as a new approach for determining the statistical significance of altered probes based on linear mixed-model. This method establishes a threshold by using different tolerance intervals that accommodates the specific random error variability observed in each test sample. RESULTS: Through simulation studies we have shown that our proposed method outperforms two existing methods that are based on simple threshold rules or iterative regression. We have illustrated the method using a controlled MLPA assay in which targeted regions are variable in copy number in individuals suffering from different disorders such as Prader-Willi, DiGeorge or Autism showing the best performace. CONCLUSION: Using the proposed mixed-model, we are able to determine thresholds to decide whether a region is altered. These threholds are specific for each individual, incorporating experimental variability, resulting in improved sensitivity and specificity as the examples with real data have revealed. BioMed Central 2008-06-04 /pmc/articles/PMC2492880/ /pubmed/18522760 http://dx.doi.org/10.1186/1471-2105-9-261 Text en Copyright © 2008 González 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 Methodology Article
González, Juan R
Carrasco, Josep L
Armengol, Lluís
Villatoro, Sergi
Jover, Lluís
Yasui, Yutaka
Estivill, Xavier
Probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (MLPA)
title Probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (MLPA)
title_full Probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (MLPA)
title_fullStr Probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (MLPA)
title_full_unstemmed Probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (MLPA)
title_short Probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (MLPA)
title_sort probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (mlpa)
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2492880/
https://www.ncbi.nlm.nih.gov/pubmed/18522760
http://dx.doi.org/10.1186/1471-2105-9-261
work_keys_str_mv AT gonzalezjuanr probespecificmixedmodelapproachtodetectcopynumberdifferencesusingmultiplexligationdependentprobeamplificationmlpa
AT carrascojosepl probespecificmixedmodelapproachtodetectcopynumberdifferencesusingmultiplexligationdependentprobeamplificationmlpa
AT armengollluis probespecificmixedmodelapproachtodetectcopynumberdifferencesusingmultiplexligationdependentprobeamplificationmlpa
AT villatorosergi probespecificmixedmodelapproachtodetectcopynumberdifferencesusingmultiplexligationdependentprobeamplificationmlpa
AT joverlluis probespecificmixedmodelapproachtodetectcopynumberdifferencesusingmultiplexligationdependentprobeamplificationmlpa
AT yasuiyutaka probespecificmixedmodelapproachtodetectcopynumberdifferencesusingmultiplexligationdependentprobeamplificationmlpa
AT estivillxavier probespecificmixedmodelapproachtodetectcopynumberdifferencesusingmultiplexligationdependentprobeamplificationmlpa