[BioC] Application of multiple testing correction in the context of using Stouffer's method for combing p-values

Claus-Dieter Mayer claus at bioss.ac.uk
Mon Mar 17 10:47:17 CET 2008

Dear Scott,

As far as I can tell your gut feeling is correct. Obviously the 
Meta-Analysis type approach you are using makes certain assumptions (the 
studies are independent, testing the same hypothesis etc...), but 
assuming those are met the the p-value you obtain from the p-value 
combination method should be a valid one, i.e it is uniformly 
distributed under the Nullhypothesis..
I see no reason why you shouldn't use the BH method on this vector of 
combined p-values (apart from the problems that you have anyway, i.e. 
dependence between genes, but that is an issue that already arises for a 
single experiment).

The only thing one should NOT do here is first to adjust p-values and 
then combine the adjusted p-values! that would give you a result that I 
wouldn't be able to interpret easily.

Best Wishes


Ochsner, Scott A wrote:
> Dear BioC community,
> I've been using a weighted Stouffer method to combing p-values (one-tailed) derived from six hgu133a microarray experiments performed by six different labs.  Each experiment roughly address the same null hypothesis:  addition of receptor ligand for 24h has no effect on gene expression.  I have then
> taken the combined Stouffer z-score and transformed it back to a two-tailed p-value.   
> #z is a vector of combined z-scores, one for each probe set in the hgu133a array.  
>> combP<-2*(pnorm(abs(z),lower.tail=FALSE))
> My question is:  Is it valid to apply multiple correction to combP similar to something like:
>> FDRcombP<-p.adjust(combP,method="BH")
> If I were doing a Venn overlap of significant probe sets from these six experiments I would be using probe sets which has passed an FDR corrected p-value threshold.  My gut is telling me to adjust the Stouffer derived significant score for multiple testing as well.
> Thanks for any feedback...
> Scott A. Ochsner, Ph.D.
> NURSA Bioinformatics
> Molecular and Cellular Biology
> Baylor College of Medicine
> Houston, TX. 77030
> phone: 713-798-6227 
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 Dr Claus-D. Mayer                    | http://www.bioss.ac.uk
 Biomathematics & Statistics Scotland | email: claus at bioss.ac.uk
 Rowett Research Institute            | Telephone: +44 (0) 1224 716652
 Aberdeen AB21 9SB, Scotland, UK.     | Fax: +44 (0) 1224 715349

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