[BioC] multiple comparisons followed by multiple tests

[Richard Friedman]

Dear Bioconductor Users,

	I have an experimental design where I have
several samples which I wish to compare in several ways
(necessitating multiple comparisons) and of course several
thousand genes (necessitating multiple tests).  My general
strategy in for analyzing these experiments is to

1. Obtain p-values for the different comparisons for each gene
corrected for multiple comparisons.

2. Correct the p-values for each test for multiple tests.

Is this correct?

	I haven't mentioned particular software so far,
because I wanted to first see if the overall approach is correct.
I am planning to use SAS because I am more comfortable with it than I am
with R at this point (I do my normalization and exploratory analysis 
with
Bioconductor and my statistical analysis with R). I planning on using
the SAS general linear model, I am planning to correct for
multiple comparisons between means with the Tukey method or a 
randomization
method. Then I am planning on correcting for multiple tests with the 
Benjamini-Hochberg
False discovery rate.

Does this sound like a reasonable way to proceed?
(I am planning on switching to R for statistical analyses eventually).

	Finally, the experimentalist gave me between 1-3 technical
replicates of each sample. I seem to remember  someone on the
list recommending that fold changes rather than statistics be used for
samples with few replicates. Are there systematic studies to back up 
this
contention?
Am i therefore wasting my time doing statistics altogether,
and should I merely rank fold changes?

This seems counterintuitive, but I need to make sure.

Thanks and best wishes,
Rich
------------------------------------------------------------
Richard A. Friedman, PhD
Associate Research Scientist
Herbert Irving Comprehensive Cancer Center
Oncoinformatics Core
Lecturer
Department of Biomedical Informatics
Box 95, Room 130BB or P&S 1-420C
Columbia University Medical Center
630 W. 168th St.
New York, NY 10032
(212)305-6901 (5-6901) (voice)
friedman at cancercenter.columbia.edu
http://cancercenter.columbia.edu/~friedman/


"What is the breakfast all those people ate on Bloomsday?"
-Rose Friedman, age 8

In Memoriam, Tim O'Connor