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Normalization of array-CGH data: influence of copy number imbalances

Staaf, Johan LU ; Jönsson, Göran B LU ; Ringnér, Markus LU and Vallon-Christersson, Johan LU (2007) In BMC Genomics 8(1).
Abstract
BACKGROUND: High-resolution microarray-based comparative genomic hybridization (CGH) techniques have successfully been applied to study copy number imbalances in a number of settings such as the analysis of cancer genomes. For normalization of array-CGH data, methods initially developed for gene expression microarray analysis have, in general, been directly adopted and used. However, these methods are designed to work under assumptions that may not be valid for array-CGH data when copy number imbalances are present. We therefore sought to investigate the effect on normalization imposed by copy number imbalances. RESULTS: Here we demonstrate that copy number imbalances correlate with intensity in array-CGH data thereby causing problems for... (More)
BACKGROUND: High-resolution microarray-based comparative genomic hybridization (CGH) techniques have successfully been applied to study copy number imbalances in a number of settings such as the analysis of cancer genomes. For normalization of array-CGH data, methods initially developed for gene expression microarray analysis have, in general, been directly adopted and used. However, these methods are designed to work under assumptions that may not be valid for array-CGH data when copy number imbalances are present. We therefore sought to investigate the effect on normalization imposed by copy number imbalances. RESULTS: Here we demonstrate that copy number imbalances correlate with intensity in array-CGH data thereby causing problems for conventional normalization methods. We propose a strategy to circumvent these problems by taking copy number imbalances into account during normalization, and we test the proposed strategy using several data sets from the analysis of cancer genomes. In addition, we show how the strategy can be applied to conveniently define adaptive sample-specific boundaries between balanced copy number, losses, and gains to facilitate management of variation in tissue heterogeneity when calling copy number changes. CONCLUSION: We highlight the importance of considering copy number imbalances during normalization of array-CGH data, and show how failure to do so can deleteriously affect data and hamper interpretation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
BMC Genomics
volume
8
issue
1
publisher
BioMed Central
external identifiers
  • pmid:17953745
  • wos:000252439300001
  • scopus:38049161350
ISSN
1471-2164
DOI
10.1186/1471-2164-8-382
project
CREATE Health
language
English
LU publication?
yes
id
dc51e52d-0b0f-4ab5-9a92-ad200a64294a (old id 1138354)
date added to LUP
2008-07-28 14:12:36
date last changed
2017-10-22 04:35:55
@article{dc51e52d-0b0f-4ab5-9a92-ad200a64294a,
  abstract     = {BACKGROUND: High-resolution microarray-based comparative genomic hybridization (CGH) techniques have successfully been applied to study copy number imbalances in a number of settings such as the analysis of cancer genomes. For normalization of array-CGH data, methods initially developed for gene expression microarray analysis have, in general, been directly adopted and used. However, these methods are designed to work under assumptions that may not be valid for array-CGH data when copy number imbalances are present. We therefore sought to investigate the effect on normalization imposed by copy number imbalances. RESULTS: Here we demonstrate that copy number imbalances correlate with intensity in array-CGH data thereby causing problems for conventional normalization methods. We propose a strategy to circumvent these problems by taking copy number imbalances into account during normalization, and we test the proposed strategy using several data sets from the analysis of cancer genomes. In addition, we show how the strategy can be applied to conveniently define adaptive sample-specific boundaries between balanced copy number, losses, and gains to facilitate management of variation in tissue heterogeneity when calling copy number changes. CONCLUSION: We highlight the importance of considering copy number imbalances during normalization of array-CGH data, and show how failure to do so can deleteriously affect data and hamper interpretation.},
  articleno    = {382},
  author       = {Staaf, Johan and Jönsson, Göran B and Ringnér, Markus and Vallon-Christersson, Johan},
  issn         = {1471-2164},
  language     = {eng},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {BMC Genomics},
  title        = {Normalization of array-CGH data: influence of copy number imbalances},
  url          = {http://dx.doi.org/10.1186/1471-2164-8-382},
  volume       = {8},
  year         = {2007},
}