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Bioinformatics Advance Access originally published online on March 31, 2008
Bioinformatics 2008 24(10):1278-1285; doi:10.1093/bioinformatics/btn109
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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.

An improved physico-chemical model of hybridization on high-density oligonucleotide microarrays

Naoaki Ono 1, Shingo Suzuki 1, Chikara Furusawa 1,2,*, Tomoharu Agata 1, Akiko Kashiwagi 1, Hiroshi Shimizu 1 and Tetsuya Yomo 1,2,3

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

*To whom correspondence should be addressed.


  Abstract

Motivation: High-density DNA microarrays provide useful tools to analyze gene expression comprehensively. However, it is still difficult to obtain accurate expression levels from the observed microarray data because the signal intensity is affected by complicated factors involving probe–target hybridization, such as non-linear behavior of hybridization, non-specific hybridization, and folding of probe and target oligonucleotides. Various methods for microarray data analysis have been proposed to address this problem. In our previous report, we presented a benchmark analysis of probe–target hybridization using artificially synthesized oligonucleotides as targets, in which the effect of non-specific hybridization was negligible. The results showed that the preceding models explained the behavior of probe–target hybridization only within a narrow range of target concentrations. More accurate models are required for quantitative expression analysis.

Results: The experiments showed that finiteness of both probe and target molecules should be considered to explain the hybridization behavior. In this article, we present an extension of the Langmuir model that reproduces the experimental results consistently. In this model, we introduced the effects of secondary structure formation, and dissociation of the probe–target duplex during washing after hybridization. The results will provide useful methods for the understanding and analysis of microarray experiments.

Availability: The method was implemented for the R software and can be downloaded from our website (http://www-shimizu.ist.osaka-u.ac.jp/shimizu_lab/FHarray/).

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

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Martin Bishop

Received on December 10, 2007; revised on March 23, 2008; accepted on March 24, 2008

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