TY - JOUR
T1 - Adaptable gene-specific dye bias correction for two-channel DNA microarrays
AU - Margaritis, Thanasis
AU - Lijnzaad, Philip
AU - Van Leenen, Dik
AU - Bouwmeester, Diane
AU - Kemmeren, Patrick
AU - Van Hooff, Sander R.
AU - Holstege, Frank C.P.
PY - 2009/1/20
Y1 - 2009/1/20
N2 - 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.
AB - 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.
KW - DNA microarrays
KW - Fluorescent dye labelling
KW - mRNA expression profiling
KW - Normalization
KW - Two channel
UR - http://www.scopus.com/inward/record.url?scp=66249121702&partnerID=8YFLogxK
U2 - 10.1038/msb.2009.21
DO - 10.1038/msb.2009.21
M3 - Article
C2 - 19401678
AN - SCOPUS:66249121702
SN - 1744-4292
VL - 5
JO - Molecular Systems Biology
JF - Molecular Systems Biology
M1 - 266
ER -