Probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (MLPA).
BMC Bioinformatics
; 9: 261, 2008 Jun 04.
Article
em En
| MEDLINE
| ID: mdl-18522760
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Sondas de DNA
/
Técnicas de Sonda Molecular
/
Dosagem de Genes
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article