Normalization and analysis of DNA microarray data by self-consistency and local regression

摘要

BackgroundWith the advent of DNA hybridization microarrays comes the remarkable ability, in principle, to simultaneously monitor the expression levels of thousands of genes. The quantiative comparison of two or more microarrays can reveal, for example, the distinct patterns of gene expression that define different cellular phenotypes or the genes induced in the cellular response to insult or changing environmental conditions. Normalization of the measured intensities is a prerequisite of such comparisons, and indeed, of any statistical analysis, yet insufficient attention has been paid to its systematic study. The most straightforward normalization techniques in use rest on the implicit assumption of linear response between true expression level and output intensity. We find that these assumptions are not generally met, and that these simple methods can be improved.