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Bioinformatics Advance Access originally published online on November 4, 2008
Bioinformatics 2008 24(24):2887-2893; doi:10.1093/bioinformatics/btn571
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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, 2Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA, 3Department of Internal Medicine and Department of Biomedical Engineering, University of Iowa, Iowa City, IA and 4Department of Health Research and Policy, Stanford University, Stanford, CA, USA

*To whom correspondence should be addressed.


  Abstract

Motivation: Microarray designs have become increasingly probe-rich, enabling targeting of specific features, such as individual exons or single nucleotide polymorphisms. These arrays have the potential to achieve quantitative high-throughput 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 cross-hybridization biases of gene-level expression estimates. Comparison with Solexa ultra high-throughput sequencing data demonstrates that correction for cross-hybridization leads to a significant improve-ment 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

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Trey Ideker

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

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