[BioC] necessity of moderated t statistic and false discoveries for small predefined gene list?

Richard Friedman friedman at cancercenter.columbia.edu
Thu May 17 04:16:38 CEST 2012

Moshe and List,

 	Thanks for yoru reply. The method you describe retains
the raw p-value based on the moderated t-statistic and adjusts
it to give an adjusted p-value (usually a false discovery rate).
However, as I understand it, the moderated
t-statistic given by Limma based on
all of the genes in the array, pools variance information
to moderate the standard deviation to prevent fortuitously
low p-values stemming from fortuitously low standard deviations
encountered in thousands of multiple tests.I am wondering
that if the experimentalist asks me to look up just 10 genes
I should use the unmoderated frequentist t-statistic which
will differ from the one in Limma and may imply significance
where Limma does not. I guess another way to phrase it is
"How many simulataneous tests does one need before one
should prefer the moderated statistic to the empirical
Bayesian one". Or should I fit just those 10 genes
(~30 affy probes) with Limma?

Best wishes,

On Thu, 17 May 2012, Moshe Olshansky wrote:

> Hi Rich,
> Whether to use the moderated t-statistic or not does not depend on whether
> you are interested in the 10 particular genes or in all differentially
> expressed ones. This will affect your multiple testing adjustment.
> The simplest way for you to proceed is to use limma as usual, get the
> topTable but then take the UNADJUSTED p-values for your 10 genes of
> interest and use the p.adjust function to adjust for multiple testing if
> you wish. In any case you should also look at (log)Fold Changes.
> Best regards,
> Moshe.
>> Dear Bioconductor  List.
>> 	I am using Limma to analyze differential expression between 2
>> conditions on an Affy chip.
>> My experimental collaborator asks for the differential  expression of
>> 10 predefined genes.
>> A, Should I correct for false discoveries based upon all of the genes
>> on the chip?
>> B. If not, should I correct for false discoveries just for the
>> probeids for the 10 predefined
>> genes?
>> C. Should I use the moderated t-statistic or just use an unmoderated t-
>> test for those 10
>> genes.
>> Thanks and best wishes,
>> Rich
>> ------------------------------------------------------------
>> Richard A. Friedman, PhD
>> Associate Research Scientist,
>> Biomedical Informatics Shared Resource
>> Herbert Irving Comprehensive Cancer Center (HICCC)
>> Lecturer,
>> Department of Biomedical Informatics (DBMI)
>> Educational Coordinator,
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>> Rose Friedman, age15
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Richard A. Friedman, PhD
Associate Research Scientist
Herbert Irving Comprehensive Cancer Center
Biomedical Informatics Shared Resource
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

"The last 250 pages of the last Harry Potter
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place in one day and nothing happened in that day."
-Rose Friedman, age 11

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