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Bioinformatics Advance Access originally published online on February 5, 2008
Bioinformatics 2008 24(6):768-774; doi:10.1093/bioinformatics/btn048
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

ITALICS: an algorithm for normalization and DNA copy number calling for Affymetrix SNP arrays

Guillem Rigaill 1,2,5,{dagger}, Philippe Hupé 1,2,3,5,*,{dagger}, Anna Almeida 4, Philippe La Rosa 1,2,5, Jean-Philippe Meyniel 4, Charles Decraene 3,4 and Emmanuel Barillot 1,2,5

1Institut Curie, Service de Bioinformatique, 2INSERM, U900, 3CNRS UMR144, 4Institut Curie, Translational Research Department, 26 rue d’Ulm, Paris F-75248 and 5Ecole des Mines de Paris, ParisTech, Fontainebleau, F-77300 France

*To whom correspondence should be addressed.


  Abstract

Motivation: Affymetrix SNP arrays can be used to determine the DNA copy number measurement of 11 000–500 000 SNPs along the genome. Their high density facilitates the precise localization of genomic alterations and makes them a powerful tool for studies of cancers and copy number polymorphism. Like other microarray technologies it is influenced by non-relevant sources of variation, requiring correction. Moreover, the amplitude of variation induced by non-relevant effects is similar or greater than the biologically relevant effect (i.e. true copy number), making it difficult to estimate non-relevant effects accurately without including the biologically relevant effect.

Results: We addressed this problem by developing ITALICS, a normalization method that estimates both biological and non-relevant effects in an alternate, iterative manner, accurately eliminating irrelevant effects. We compared our normalization method with other existing and available methods, and found that ITALICS outperformed these methods for several in-house datasets and one public dataset. These results were validated biologically by quantitative PCR.

Availability: The R package ITALICS (ITerative and Alternative normaLIzation and Copy number calling for affymetrix Snp arrays) has been submitted to Bioconductor.

Contact: italics{at}curie.fr

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Chris Stoeckert

{dagger}The authors wish to be known that, in their opinion, the first two authors should be regarded as joint First Authors.

Received on August 21, 2007; revised on January 29, 2008; accepted on January 29, 2008

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