[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,
Rich



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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>>
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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
Lecturer
Department of Biomedical Informatics
Box 95, Room 130BB or P&S 1-420C
Columbia University Medical Center
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"The last 250 pages of the last Harry Potter
book took place in one day because alot
happened in that day. All of Ulysses takes
place in one day and nothing happened in that day."
-Rose Friedman, age 11



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