Adaptable gene‐specific dye bias correction for two‐channel DNA microarrays

Abstract DNA microarray technology is a powerful tool for monitoring gene expression or for finding the location of DNA‐bound proteins. DNA microarrays can suffer from gene‐specific dye bias (GSDB), causing some probes to be affected more by the dye than by the sample. This results in large measurem...

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Main Authors: Thanasis Margaritis, Philip Lijnzaad, Dik van Leenen, Diane Bouwmeester, Patrick Kemmeren, Sander R van Hooff, Frank CP Holstege
Format: Article
Language:English
Published: Springer Nature 2009-04-01
Series:Molecular Systems Biology
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Online Access:https://doi.org/10.1038/msb.2009.21
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author Thanasis Margaritis
Philip Lijnzaad
Dik van Leenen
Diane Bouwmeester
Patrick Kemmeren
Sander R van Hooff
Frank CP Holstege
author_facet Thanasis Margaritis
Philip Lijnzaad
Dik van Leenen
Diane Bouwmeester
Patrick Kemmeren
Sander R van Hooff
Frank CP Holstege
author_sort Thanasis Margaritis
collection DOAJ
description Abstract DNA microarray technology is a powerful tool for monitoring gene expression or for finding the location of DNA‐bound proteins. DNA microarrays can suffer from gene‐specific dye bias (GSDB), causing some probes to be affected more by the dye than by the sample. This results in large measurement errors, which vary considerably for different probes and also across different hybridizations. GSDB is not corrected by conventional normalization and has been difficult to address systematically because of its variance. We show that GSDB is influenced by label incorporation efficiency, explaining the variation of GSDB across different hybridizations. A correction method (Gene‐ And Slide‐Specific Correction, GASSCO) is presented, whereby sequence‐specific corrections are modulated by the overall bias of individual hybridizations. GASSCO outperforms earlier methods and works well on a variety of publically available datasets covering a range of platforms, organisms and applications, including ChIP on chip. A sequence‐based model is also presented, which predicts which probes will suffer most from GSDB, useful for microarray probe design and correction of individual hybridizations. Software implementing the method is publicly available.
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spelling doaj-art-30df98edcc8f49bcbae66c69663bf88a2025-08-20T02:18:33ZengSpringer NatureMolecular Systems Biology1744-42922009-04-01511610.1038/msb.2009.21Adaptable gene‐specific dye bias correction for two‐channel DNA microarraysThanasis Margaritis0Philip Lijnzaad1Dik van Leenen2Diane Bouwmeester3Patrick Kemmeren4Sander R van Hooff5Frank CP Holstege6Department of Physiological Chemistry, University Medical Center Utrecht, UniversiteitswegDepartment of Physiological Chemistry, University Medical Center Utrecht, UniversiteitswegDepartment of Physiological Chemistry, University Medical Center Utrecht, UniversiteitswegDepartment of Physiological Chemistry, University Medical Center Utrecht, UniversiteitswegDepartment of Physiological Chemistry, University Medical Center Utrecht, UniversiteitswegDepartment of Physiological Chemistry, University Medical Center Utrecht, UniversiteitswegDepartment of Physiological Chemistry, University Medical Center Utrecht, UniversiteitswegAbstract DNA microarray technology is a powerful tool for monitoring gene expression or for finding the location of DNA‐bound proteins. DNA microarrays can suffer from gene‐specific dye bias (GSDB), causing some probes to be affected more by the dye than by the sample. This results in large measurement errors, which vary considerably for different probes and also across different hybridizations. GSDB is not corrected by conventional normalization and has been difficult to address systematically because of its variance. We show that GSDB is influenced by label incorporation efficiency, explaining the variation of GSDB across different hybridizations. A correction method (Gene‐ And Slide‐Specific Correction, GASSCO) is presented, whereby sequence‐specific corrections are modulated by the overall bias of individual hybridizations. GASSCO outperforms earlier methods and works well on a variety of publically available datasets covering a range of platforms, organisms and applications, including ChIP on chip. A sequence‐based model is also presented, which predicts which probes will suffer most from GSDB, useful for microarray probe design and correction of individual hybridizations. Software implementing the method is publicly available.https://doi.org/10.1038/msb.2009.21DNA microarraysfluorescent dye labellingmRNA expression profilingnormalizationtwo channel
spellingShingle Thanasis Margaritis
Philip Lijnzaad
Dik van Leenen
Diane Bouwmeester
Patrick Kemmeren
Sander R van Hooff
Frank CP Holstege
Adaptable gene‐specific dye bias correction for two‐channel DNA microarrays
Molecular Systems Biology
DNA microarrays
fluorescent dye labelling
mRNA expression profiling
normalization
two channel
title Adaptable gene‐specific dye bias correction for two‐channel DNA microarrays
title_full Adaptable gene‐specific dye bias correction for two‐channel DNA microarrays
title_fullStr Adaptable gene‐specific dye bias correction for two‐channel DNA microarrays
title_full_unstemmed Adaptable gene‐specific dye bias correction for two‐channel DNA microarrays
title_short Adaptable gene‐specific dye bias correction for two‐channel DNA microarrays
title_sort adaptable gene specific dye bias correction for two channel dna microarrays
topic DNA microarrays
fluorescent dye labelling
mRNA expression profiling
normalization
two channel
url https://doi.org/10.1038/msb.2009.21
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AT philiplijnzaad adaptablegenespecificdyebiascorrectionfortwochanneldnamicroarrays
AT dikvanleenen adaptablegenespecificdyebiascorrectionfortwochanneldnamicroarrays
AT dianebouwmeester adaptablegenespecificdyebiascorrectionfortwochanneldnamicroarrays
AT patrickkemmeren adaptablegenespecificdyebiascorrectionfortwochanneldnamicroarrays
AT sanderrvanhooff adaptablegenespecificdyebiascorrectionfortwochanneldnamicroarrays
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