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Open Access Methodology article

Spatial normalization improves the quality of genotype calling for Affymetrix SNP 6.0 arrays

High Seng Chai, Terry M Therneau, Kent R Bailey and Jean-Pierre A Kocher*

Author Affiliations

Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

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BMC Bioinformatics 2010, 11:356  doi:10.1186/1471-2105-11-356

Published: 29 June 2010

Abstract

Background

Microarray measurements are susceptible to a variety of experimental artifacts, some of which give rise to systematic biases that are spatially dependent in a unique way on each chip. It is likely that such artifacts affect many SNP arrays, but the normalization methods used in currently available genotyping algorithms make no attempt at spatial bias correction. Here, we propose an effective single-chip spatial bias removal procedure for Affymetrix 6.0 SNP arrays or platforms with similar design features. This procedure deals with both extreme and subtle biases and is intended to be applied before standard genotype calling algorithms.

Results

Application of the spatial bias adjustments on HapMap samples resulted in higher genotype call rates with equal or even better accuracy for thousands of SNPs. Consequently the normalization procedure is expected to lead to more meaningful biological inferences and could be valuable for genome-wide SNP analysis.

Conclusions

Spatial normalization can potentially rescue thousands of SNPs in a genetic study at the small cost of computational time. The approach is implemented in R and available from the authors upon request.