[BioC] Multiple hypothesis correction and pairwise tests

[Adaikalavan RAMASAMY]

Dear all,

Apologies if this is off-topic but I have been pondering about multiple correction procedures when multiple groups are involved.

In a microarray context, say we have 20000 probes/genes and the responses are either Grade 1, 2, 3 (assume all arrays correspond to some tumor). The null hypothesis is that the gene expression means does not vary between the three levels of the grade.

Suppose, I perform a pairwise t-test for these 3 grade on a gene-by-gene basis resulting in 3 p-values for each gene. Do I adjust the p-value within each gene using some multiple correction technique followed adjustment for multiple hypothesis for 20000 probes ? Or just perform the adjustment for multiple probes only ?

The other solution I have is to perform F-test, adjust the F-test p-values and select top $n$ genes. Then perform pairwise t-test on the $n$ genes with adjustment to determine which group and how many group means differ. I think this is the more sensible method. My second question is which of these methods better ?

Many thanks in advance.

Regards, Adaikalavan Ramasamy.