[BioC] how to test for genes of interest?

[Jenny Drnevich]

Hi everyone,

I've always heard that one of the ways "around" the multiple testing 
problem of microarrays is for you to a priori identify a particular 
list of genes you're interested in, and then you only have to do the 
multiple test correction for this smaller list. I've never done this 
in practice, and I'm not sure at what point in the analysis it's 
proper to pull out just the smaller list. Obviously, all the data 
preprocessing and normalization will be done with all the genes, but 
should I pull out the genes before fitting the model, or after 
fitting the model right before the multiple test adjustment? I'm 
using the eBayes() shrinkage in limma, so which genes are in the 
model will make a big difference in the outcome.

I'm thinking it would be best to keep all the genes in the model, and 
then split them out into two groups (genes of interest and all the 
rest) and do a FDR correction separately for each group. What do you think?

Thanks,
Jenny

Jenny Drnevich, Ph.D.

Functional Genomics Bioinformatics Specialist
W.M. Keck Center for Comparative and Functional Genomics
Roy J. Carver Biotechnology Center
University of Illinois, Urbana-Champaign

330 ERML
1201 W. Gregory Dr.
Urbana, IL 61801
USA

ph: 217-244-7355
fax: 217-265-5066
e-mail: drnevich at illinois.edu