[BioC] Conservative results using DEXSeq

[Simon Anders]

Hi

On 23/07/13 14:47, Gu [guest] wrote:
> By checking the histogram of raw p-values of exons (NOT genes), I
> find that it is monotonically increasing from 0 to 1, with relatively
> few counting bins falling into the bins from 0 to 0.2.

You are right, DEXSeq sometimes tends to be overly conservative, which 
then results in a skewed p value histogram as you describe it. Usually, 
it is, however, only a rather slight skew, and it seems that the 
performance is unusually bad for your specific dataset.

The main reason for the conservative results is the way we estimate 
dispersion. Since the release of DEXSeq, we have made quite some 
progress in improving the dispersion estimation by now using an 
empirical-Bayes shrinkage estimator, and DESeq2 now offers a much better 
solution, at least for gene-level tests. We are working on applying the 
same changes to DEXSeq, and this should solve your issue. I'm afraid, 
however, that I have to ask you for some patience until we are finished 
with these changes.

   Simon