Normality of gene expression revisited

作者：Chen Linlin^*; Klebanov Lev; Yakovlev Andrei

来源：Journal of Biological Systems, 2007, 15(1): 39-48.

DOI：10.1142/S0218339007002027

• gene expression
• microarray data
• goodness-of-fit
• normality
• resampling

A question has been raised in several publications as to whether or not the expression levels or their logarithms for different genes are normally distributed. To answer this question would require a large data set where both biological variability and technological noise are present. An earlier attempt to test this assumption was limited to technical replicates and did not take multiplicity of tests into account when assessing the net results of goodness-of-fit testing. Therefore, the problem calls for further exploration. We applied several statistical tests to a large set of high-density oligonucleotide microarray data in order to systematically test for log-normality of expression levels for all the reporter genes. The multiple testing aspect of the problem was addressed by designing a pertinent resampling procedure. The results of testing did not reject normality of log-intensities in the non-normalized data under study. However, the global log-normality hypothesis was rejected beyond all reasonable doubt when the data were normalized by the quantile normalization procedure. Our results are consistent with the hypothesis that non-normalized expression levels of different genes are approximately log-normally distributed. The quantile normalization causes dramatic changes in the shape of marginal distributions of log-intensities which may be an indication that this procedure interferes not only in the technological noise but the true biological signal as well. This possibility invites a special investigation.

• 出版日期2007-3