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Bioinformatics Advance Access originally published online on November 2, 2005
Bioinformatics 2006 22(1):7-12; doi:10.1093/bioinformatics/bti741
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A genotype calling algorithm for affymetrix SNP arrays

Nusrat Rabbee 1,* and Terence P. Speed 1,2

1Department of Statistics, University of California Berkeley, CA, USA
2Walter and Eliza Hall Institute of Medical Research Melbourne, Australia

*To whom correspondence should be addressed.

Motivation: A classification algorithm, based on a multi-chip, multi-SNP approach is proposed for Affymetrix SNP arrays. Current procedures for calling genotypes on SNP arrays process all the features associated with one chip and one SNP at a time. Using a large training sample where the genotype labels are known, we develop a supervised learning algorithm to obtain more accurate classification results on new data. The method we propose, RLMM, is based on a robustly fitted, linear model and uses the Mahalanobis distance for classification. The chip-to-chip non-biological variance is reduced through normalization. This model-based algorithm captures the similarities across genotype groups and probes, as well as across thousands of SNPs for accurate classification. In this paper, we apply RLMM to Affymetrix 100 K SNP array data, present classification results and compare them with genotype calls obtained from the Affymetrix procedure DM, as well as to the publicly available genotype calls from the HapMap project.

Availability: The RLMM software is implemented in R and is available from Bioconductor or from the first author at nrabbee{at}post.harvard.edu.

Contact: nrabbee{at}stat.berkeley.edu

Supplementary information: http://www.stat.berkeley.edu/users/nrabbee/693.pdf

Received on July 26, 2005; revised on September 28, 2005; accepted on October 21, 2005

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