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

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 hybri...

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Autores principales: Ono, Naoaki, Suzuki, Shingo, Furusawa, Chikara, Agata, Tomoharu, Kashiwagi, Akiko, Shimizu, Hiroshi, Yomo, Tetsuya
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373920/
https://www.ncbi.nlm.nih.gov/pubmed/18378525
http://dx.doi.org/10.1093/bioinformatics/btn109
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author Ono, Naoaki
Suzuki, Shingo
Furusawa, Chikara
Agata, Tomoharu
Kashiwagi, Akiko
Shimizu, Hiroshi
Yomo, Tetsuya
author_facet Ono, Naoaki
Suzuki, Shingo
Furusawa, Chikara
Agata, Tomoharu
Kashiwagi, Akiko
Shimizu, Hiroshi
Yomo, Tetsuya
author_sort Ono, Naoaki
collection PubMed
description 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.
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spelling pubmed-23739202009-02-25 An improved physico-chemical model of hybridization on high-density oligonucleotide microarrays Ono, Naoaki Suzuki, Shingo Furusawa, Chikara Agata, Tomoharu Kashiwagi, Akiko Shimizu, Hiroshi Yomo, Tetsuya Bioinformatics Original Papers 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. Oxford University Press 2008-05-15 2008-03-31 /pmc/articles/PMC2373920/ /pubmed/18378525 http://dx.doi.org/10.1093/bioinformatics/btn109 Text en © 2008 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ 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.
spellingShingle Original Papers
Ono, Naoaki
Suzuki, Shingo
Furusawa, Chikara
Agata, Tomoharu
Kashiwagi, Akiko
Shimizu, Hiroshi
Yomo, Tetsuya
An improved physico-chemical model of hybridization on high-density oligonucleotide microarrays
title An improved physico-chemical model of hybridization on high-density oligonucleotide microarrays
title_full An improved physico-chemical model of hybridization on high-density oligonucleotide microarrays
title_fullStr An improved physico-chemical model of hybridization on high-density oligonucleotide microarrays
title_full_unstemmed An improved physico-chemical model of hybridization on high-density oligonucleotide microarrays
title_short An improved physico-chemical model of hybridization on high-density oligonucleotide microarrays
title_sort improved physico-chemical model of hybridization on high-density oligonucleotide microarrays
topic Original Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373920/
https://www.ncbi.nlm.nih.gov/pubmed/18378525
http://dx.doi.org/10.1093/bioinformatics/btn109
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