Normalization of Illumina Infinium whole-genome SNP data improves copy number estimates and allelic intensity ratios

Background: Illumina Infinium whole genome genotyping (WGG) arrays are increasingly being applied in cancer genomics to study gene copy number alterations and allele-specific aberrations such as loss-of-heterozygosity (LOH). Methods developed for normalization of WGG arrays have mostly focused on diploid, normal samples. However, for cancer samples genomic aberrations may confound normalization and data interpretation. Therefore, we examined the effects of the conventionally used normalization method for Illumina Infinium arrays when applied to cancer samples. Results: We demonstrate an asymmetry in the detection of the two alleles for each SNP, which deleteriously influences both allelic proportions and copy number estimates. The asymmetry is caused by a remaining bias between the two dyes used in the Infinium II assay after using the normalization method in Illumina's proprietary software (BeadStudio). We propose a quantile normalization strategy for correction of this dye bias...

• Type: Journal
• Year: 2008
• Where: BMCBI
• Authors: Johan Staaf, Johan Vallon-Christersson, David Lindgren, Gunnar Juliusson, Richard Rosenquist, Mattias Höglund, Åke Borg, Markus Ringnér
• Keywords: BMCBI 2008, Illumina Infinium, Normalization Method, Normalization Strategy