Journal Article

Cross-hybridization modeling on Affymetrix exon arrays

Karen Kapur, Hui Jiang, Yi Xing and Wing Hung Wong

in Bioinformatics

Volume 24, issue 24, pages 2887-2893
Published in print December 2008 | ISSN: 1367-4803
Published online November 2008 | e-ISSN: 1460-2059 | DOI: http://dx.doi.org/10.1093/bioinformatics/btn571

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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@stanford.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

Journal Article.  5748 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology

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