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

@article{citeulike:2766637, 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@ist.osaka-u.ac.jp Supplementary information: Supplementary data are available at Bioinformatics online. 10.1093/bioinformatics/btn109}, author = {Ono, Naoaki and Suzuki, Shingo and Furusawa, Chikara and Agata, Tomoharu and Kashiwagi, Akiko and Shimizu, Hiroshi and Yomo, Tetsuya }, citeulike-article-id = {2766637}, doi = {10.1093/bioinformatics/btn109}, journal = {Bioinformatics}, keywords = {algorithm, microarray, normalization, r}, month = {May}, number = {10}, pages = {1278--1285}, posted-at = {2008-05-17 18:08:10}, priority = {2}, title = {An improved physico-chemical model of hybridization on high-density oligonucleotide microarrays}, url = {http://dx.doi.org/10.1093/bioinformatics/btn109}, volume = {24}, year = {2008} }

TY - JOUR ID - citeulike:2766637 L3 - citeulike-article-id:2766637 TI - An improved physico-chemical model of hybridization on high-density oligonucleotide microarrays JF - Bioinformatics VL - 24 IS - 10 SP - 1278 EP - 1285 N2 - 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@ist.osaka-u.ac.jp Supplementary information: Supplementary data are available at Bioinformatics online. 10.1093/bioinformatics/btn109 KW - algorithm KW - microarray KW - normalization KW - r AU - Ono, Naoaki AU - Suzuki, Shingo AU - Furusawa, Chikara AU - Agata, Tomoharu AU - Kashiwagi, Akiko AU - Shimizu, Hiroshi AU - Yomo, Tetsuya PY - 2008/05/15/ UR - http://dx.doi.org/10.1093/bioinformatics/btn109 ER -