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Bioinformatics Advance Access originally published online on October 31, 2008
Bioinformatics 2009 25(1):36-41; doi:10.1093/bioinformatics/btn570
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Model-based analysis of non-specific binding for background correction of high-density oligonucleotide microarrays

Chikara Furusawa 1,2,*,{dagger}, Naoaki Ono 1,{dagger}, Shingo Suzuki 1, Tomoharu Agata 1, Hiroshi Shimizu 1 and Tetsuya Yomo 1,2,3

1Department of Bioinformatics Engineering, Graduate School of Information Science and Technology, Osaka University, 2Complex Systems Biology Project, ERATO and 3Graduate School of Frontier Biosciences, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan

*To whom correspondence should be addressed.


  Abstract

Motivation: High-density DNA microarrays provide us with useful tools for analyzing DNA and RNA comprehensively. However, the background signal caused by the non-specific binding (NSB) between probe and target makes it difficult to obtain accurate measurements. To remove the background signal, there is a set of background probes on Affymetrix Exon arrays to represent the amount of non-specific signals, and an accurate estimation of non-specific signals using these background probes is desirable for improvement of microarray analyses.

Results: We developed a thermodynamic model of NSB on short nucleotide microarrays in which the NSBs are modeled by duplex formation of probes and multiple hypothetical targets. We fitted the observed signal intensities of the background probes with those expected by the model to obtain the model parameters. As a result, we found that the presented model can improve the accuracy of prediction of non-specific signals in comparison with previously proposed methods. This result will provide a useful method to correct for the background signal in oligonucleotide microarray analysis.

Availability: The software is implemented in the R language and can be downloaded from our website (http://www-shimizu.ist.osaka-u.ac.jp/shimizu_lab/MSNS/).

Contact: furusawa{at}ist.osaka-u.ac.jp

Supplementary information: Supplementary data are available at Bioinformatics online.

{dagger}The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.

Associate Editor: Trey Ideker

Received on June 17, 2008; revised on September 16, 2008; accepted on October 30, 2008

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