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Series GSE11977 Query DataSets for GSE11977
Status Public on Oct 04, 2008
Title Normalization of Illumina Infinium whole-genome SNP data improves copy number estimates and allelic intensity ratios
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
Summary 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.

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. We tested the normalization strategy using 535 individual hybridizations from 10 data sets from the analysis of cancer genomes and normal blood samples generated on Illumina Infinium II 300k version 1 and 2, 370k and 550k BeadChips. We show that the proposed normalization strategy successfully removes asymmetry in estimates of both allelic proportions and copy numbers. Additionally, the normalization strategy reduces the technical variation for copy number estimates while retaining the response to copy number alterations.

The proposed normalization strategy represents a valuable low-level analysis tool that improves the quality of data obtained from Illumina Infinium arrays, in particular when used for LOH and copy number variation studies.
 
Overall design To investigate the effects of a quantile normalization of Illumina Infinium data, compared to conventional normalization using BeadStudio (www.illumina.com), we renormalized 535 individual hybridizations conducted on Illumina 300K, 370K and 550K BeadChips. Sample types included breast cancer, colon cancer, urothelial carcinoma, leukemia as well as normal blood and HapMap samples. This series includes the 6 breast cancers hybridized on Illumina HumanHap 550K BeadChips.
Web link http://baseplugins.thep.lu.se/wiki/se.lu.onk.IlluminaSNPNormalization
 
Contributor(s) Staaf J, Vallon-Christersson J, Lindgren D, Juliusson G, Rosenquist R, Höglund M, Borg A, Ringner M
Citation(s) 18831757
Submission date Jul 03, 2008
Last update date Mar 19, 2012
Contact name Johan Staaf
Organization name SCIBLU - Swegene Centre for Integrative Biology at Lund University
Street address Medicon Village
City Lund
ZIP/Postal code SE-223 81
Country Sweden
 
Platforms (1)
GPL6981 Illumina HumanHap550v3 Genotyping BeadChip (HumanHap550v3_B)
Samples (6)
GSM302898 BT3
GSM302899 BT1
GSM302901 BT2
Relations
BioProject PRJNA105855

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE11977_GEO_6samples_Breast_INT_550k.txt 99.8 Mb (ftp)(http) TXT
GSE11977_RAW.tar 59.4 Mb (http)(custom) TAR
Processed data included within Sample table
Processed data provided as supplementary file

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