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Bioinformatics Advance Access published online on November 4, 2008
Bioinformatics, doi:10.1093/bioinformatics/btn571
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© The Author (2008). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Cross-Hybridization Modeling on Affymetrix Exon Arrays

Karen Kapur 1, Hui Jiang 2, Yi Xing 3 and Wing Hung Wong 1,4,*

1Department of Statistics, Stanford University
2Institute for Computational and Mathematical Engineering, Stanford University
3Department of Internal Medicine and Department of Biomedical Engineering, University of Iowa
4Department of Health Research and Policy, Stanford University

*To whom correspondence should be addressed. Prof. Wing Hung Wong, E-mail: whwong{at}stanford.edu


  Abstract

Motivation: Microarray designs have become increasingly proberich, enabling targeting of specific features, such as individual exons or SNPs. These arrays have the potential to achieve quantitative highthroughput estimates of transcript abundances, but currently these estimates are affected by biases due to cross-hybridization, in which probes hybridize to off-target transcripts.

Results: To study cross-hybridization, we map Affymetrix exon array probes to a set of annotated mRNA transcripts, allowing a small number of mismatches or insertion-deletions between the two sequences. Based on a systematic study of the degree to which probes with a given match type to a transcript are affected by cross-hybridization, we developed a strategy to correct for crosshybridization biases of gene-level expression estimates. Comparison with Solexa ultra-high-throughput sequencing data demonstrates that correction for cross-hybridization leads to a significant improvement of gene expression estimates.

Availability: We provide mappings between human and mouse exon array probes and off-target transcripts and provide software extending the GeneBASE program for generating gene-level expression estimates including the cross-hybridization correction http://biogibbs.stanford.edu/~kkapur/GeneBase/.

Contact: whwong{at}stanford.edu

Associate Editor: Dr. Trey Ideker

Received on July 15, 2008; revised on October 3, 2008; accepted on October 30, 2008

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