[BioC] Most diff exp genes are up-regulated... can this be true?

[Peter Davidsen]

Dear List,

I'm analysing some one-color microarray data generated using a custom
designed Agilent array (their 8 x 60K platform).
When I compare control samples to treated ones most (i.e. >80%) of the
differentially expressed transcripts are up-regulated. This pronounced
up-regulation is independent of type of treatment.
I have never before experienced such a quantitative difference in the
number of up- and down-regulated transcripts. Furthermore, I have
tried to analyse relevant datasets in the GEO that mimics my study
design in terms of treatment regime, duration of treatment ect. These
analyses--all in closely related species--suggest that the fraction of
up and down-regulated transcripts should be roughly the same.
The QC reports generated by the Agilent Feature Extraction Software
indicate that the data quality should be fine. Also a few basic
boxplot before and after normalization haven't raised my suspicion. I
do, however, find that the median signal intensity for each sample is
significantly lower than what I've seen in the past with the same
platform (although targeted against another related species).
I have tried to normalize my data using both quantile and vsn,
respectively, with similar result. I have also tried to filter my
dataset using different intensity filters - again with similar result.
And finally, I also tried using both limma and SAMR for the
statistics.

Have anyone by any chance experienced something similar, and how did
you deal with this issue of many siggenes going in one direction?

Many thanks,
Peter