Non-linear normalization and background correction in one-channel cDNA microarray studies.
BACKGROUND
Data from one-channel cDNA microarray studies may exhibit poor reproducibility due to spatial heterogeneity, non-linear array-to-array variation and problems in correcting for background. Uncorrected, these phenomena can give rise to misleading conclusions.


RESULTS
Spatial heterogeneity may be corrected using two-dimensional loess smoothing (Colantuoni et al., 2002). Non-linear between-array variation may be corrected using an iterative application of one-dimensional loess smoothing. A method for background correction using a smoothing function rather than simple subtraction is described. These techniques promote within-array spatial uniformity and between-array reproducibility. Their application is illustrated using data from a study of the effects of an insulin sensitizer, rosiglitazone, on gene expression in white adipose tissue in diabetic db/db mice. They may also be useful with data from two-channel cDNA microarrays and from oligonucleotide arrays.


BACKGROUND
R functions for the methods described are available on request from the author.
Edwards
David
D
Department of Biostatistics, Novo Nordisk, Bagsvaerd, Denmark. DEd@novonordisk.com
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D016477:Artifacts; D002232:Carbocyanines; D020869:Gene Expression Profiling / Q000379:methods* / Q000592:standards; D008297:Male; D051379:Mice; D008957:Models, Genetic; D015233:Models, Statistical; D017711:Nonlinear Dynamics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000592:standards; D011786:Quality Control; D012313:RNA / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods* / Q000592:standards; D013269:Stochastic Processes
D002232:Carbocyanines; C089187:cyanine dye 3; C085321:cyanine dye 5; D012313:RNA