4.5 Article

Testing for differentially-expressed genes by maximum-likelihood analysis of microarray data

Journal

JOURNAL OF COMPUTATIONAL BIOLOGY
Volume 7, Issue 6, Pages 805-817

Publisher

MARY ANN LIEBERT INC PUBL
DOI: 10.1089/10665270050514945

Keywords

DNA microarray; gene expression; maximum likelihood; statistical error analysis; yeast

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Although two-color fluorescent DNA microarrays are now standard equipment in many molecular biology laboratories, methods for identifying differentially expressed genes in microarray data are still evolving. Here, we report a refined test for differentially expressed genes which does not rely on gene expression ratios but directly compares a series of repeated measurements of the two dye intensities for each gene. This test uses a statistical model to describe multiplicative and additive errors influencing an array experiment, where model parameters are estimated from observed intensities for all genes using the method of maximum likelihood, A generalized likelihood ratio test is performed for each gene to determine whether, under the model, these intensities are significantly different. We use this method to identify significant differences in gene expression among yeast cells growing in galactose-stimulating versus non-stimulating conditions and compare our results with current approaches for identifying differentially-expressed genes. The effect of sample size on parameter optimization is also explored, as is the use of the error model to compare the within- and between-slide intensity variation intrinsic to an array experiment.

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