An adaptive method for cDNA microarray normalization.
BACKGROUND
Normalization is a critical step in analysis of gene expression profiles. For dual-labeled arrays, global normalization assumes that the majority of the genes on the array are non-differentially expressed between the two channels and that the number of over-expressed genes approximately equals the number of under-expressed genes. These assumptions can be inappropriate for custom arrays or arrays in which the reference RNA is very different from the experimental samples.


RESULTS
We propose a mixture model based normalization method that adaptively identifies non-differentially expressed genes and thereby substantially improves normalization for dual-labeled arrays in settings where the assumptions of global normalization are problematic. The new method is evaluated using both simulated and real data.


CONCLUSIONS
The new normalization method is effective for general microarray platforms when samples with very different expression profile are co-hybridized and for custom arrays where the majority of genes are likely to be differentially expressed.
Zhao
Yingdong
Y
Biometric Research Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA. zhaoy@helix.nih.gov
Li
Ming-Chung
MC
Simon
Richard
R
D002138:Calibration; D019295:Computational Biology / Q000379:methods*; D018076:DNA, Complementary / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D015870:Gene Expression; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015233:Models, Statistical; D015999:Multivariate Analysis; D016011:Normal Distribution; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012313:RNA / Q000737:chemistry; D012334:RNA, Neoplasm; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D018076:DNA, Complementary; D015345:Oligonucleotide Probes; D012334:RNA, Neoplasm; D012313:RNA