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BMC Bioinformatics 2005
Can Zipf's law be adapted to normalize microarrays?Abstract: Using pairwise comparisons using MA plots (log ratio vs. log intensity), we compared this novel method to previously published normalization techniques, namely global normalization to the mean, the quantile method, and a variation on the loess normalization method designed specifically for boutique microarrays. Results indicated that, for single channel microarrays, the quantile method was superior with regard to eliminating intensity-dependent effects (banana curves), but Zipf's law normalization does minimize this effect by rotating the data distribution such that the maximal number of data points lie on the zero of the log ratio axis. For two channel boutique microarrays, the Zipf's law normalizations performed as well as, or better than existing techniques.Zipf's law normalization is a useful tool where the Quantile method cannot be applied, as is the case with microarrays containing functionally specific gene sets (boutique arrays).DNA microarrays have become a widely used biotechnology for assessing expression levels of tens of thousands of genes simultaneously in a single experiment [1,2]. Whether microarrays are being used for global tissue profiling or for differential expression studies, data normalization is an essential preliminary step before statistical analysis methods can be applied. The purpose of all normalization techniques is to transform the data to eliminate sources of variability stemming from experimental conditions, leaving only biologically relevant differences in gene expression for subsequent analysis. Normalization can be divided into two stages, intra-array normalization and inter-array normalization. Intra-array normalization deals with variability within a single array caused by factors such as differences in print-tip characteristics, channel differences in two-dye systems, and spatial heterogeneity across the array surface [3-5] and should be carried out using accepted methods before inter-array normalization is applied. This paper
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