[BioC] (control vs treatment) in (wildtype vs mutant) microarray analysis

[Cheng-Yuan Kao]

We have done affy microarrays for wildtype-control treatment,
wildtype-toxin treatment, mutant-control treatment and mutant-toxin
treatment.

The goal is to find diffferentially expressed genes regulated by toxin
in wildtype and then find out which of these regulation are mutant
dependent.


The first goal is typical. So we did R/ bioconductor - SAM and limma.
Both could give us a bunch of DEGs. However, I am lost about getting
the second aim done.
With limma and 2x2 factorial analysis, we could find the DEGs from all
kind of pairs, such as wildtype -Toxin/control (this answers the first
goal) or mutant/wildtype in control treatment (this tells us how the
mutant gene is affecting the basal expression without toxin).
But I don't know how to find the wildtype DEGs which have regulation
depending on the mutant gene. Say one gene is up-regulated 100 folds
by toxin (i.e. toxin treatment/control treatment) in wildtype. Then if
this gene is up-regulated 3 folds (toxin treatment/control treatment)
in mutant, it will be apparently mutant gene dependent (from 100 folds
in wildtype to 3 folds in mutant). However, this gene will be shown as
DEG in the mutant analysis as well since it is more than the 2-fold
cutoff. Then if I only compared the DEGs in different pair of analysis
from limma, I will miss these kind of genes. There must be some
dedicated way to analyze this but I could not find it. Any suggestion
will be appreciated. Thanks a lot.