Bioinformatics Advance Access published online on March 31, 2008
Bioinformatics, doi:10.1093/bioinformatics/btn109
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An improved physico-chemical model of hybridization on high-density oligonucleotide microarrays.
1Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
2Complex Systems Biology Project, ERATO, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
3Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka565-0871, Japan
*To whom correspondence should be addressed. Dr. Naoaki ONO, E-mail: nono{at}bio.eng.osaka-u.ac.jp
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Abstract |
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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 nonlinear behavior of hybridization, nonspecific 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 (Suzuki et al., 2007a), we presented a benchmark analysis of probe-target hybridization using artificially synthesized oligonucleotides as targets, in which the effect of nonspecific 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 paper, we present an extension of the Langmuirmodel 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.
Contact: furusawa{at}ist.osaka-u.ac.jp
Availability: The method was implemented for the R software and can be downloaded from the Bioconductor project website (http://www.bioconductor.org).
Associate Editor: Prof. Martin Bishop
Received on December 10, 2007; revised on March 23, 2008; accepted on March 24, 2008
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