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Journal Article

Variance stabilization applied to microarray data calibration and to the quantification of differential expression

MPS-Authors

von Heydebreck,  Anja
Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50613

Vingron,  Martin
Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Huber, W., von Heydebreck, A., Sültmann, H., Poustka, A., & Vingron, M. (2002). Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Proceedings of the Tenth International Conference on Intelligent Systems for Molecular Biology, S96-S104.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-8BDC-B
Abstract
We introduce a statistical model for microarray gene expression data that comprises data calibration, the quantification of differential expression, and the quantification of measurement error. In particular, we derive a transformation h for intensity measurements, and a difference statistic h whose variance is approximately constant along the whole intensity range. This forms a basis for statistical inference from microarray data, and provides a rational data pre-processing strategy for multivariate analyses. For the transformation h, the parametric form h(x)=arsinh(a+bx) is derived from a model of the variance-versus-mean dependence for microarray intensity data, using the method of variance stabilizing transformations. For large intensities, h coincides with the logarithmic transformation, and h with the log-ratio. The parameters of h together with those of the calibration between experiments are estimated with a robust variant of maximum-likelihood estimation. We demonstrate our approach on data sets from different experimental platforms, including two-colour cDNA arrays and a series of Affymetrix oligonucleotide arrays.