[BioC] Now I get it(almost)

Richard Friedman friedman at cancercenter.columbia.edu
Fri Aug 6 21:48:00 CEST 2004


Gordon,

	I now believe that I understand your answer. In order to do adjust for 
both  multiple comparisons and
multiple tests I use classifyTestsF() with method="fdr". If I 
understand the documentation correctly, the fdr part
refers to the multiple test correction across genes on top of the 
multiple comparison adjustment across levels performed
  if no method were to be specified.

	Do I have it straight?

Thanks and best wishes,
Rich
On Aug 6, 2004, at 9:57 AM, Gordon Smyth wrote:

> At 11:36 PM 6/08/2004, Richard Friedman wrote:
>> Gordon,
>>
>>         Thank you for answering my questions. The last equation in 
>> your paper makes intuitive sense to me.
>>
>>         I'm wondering if you can take the time to answer two  more 
>> questions:
>>
>> 1. Say I have the following case:
>>
>> Level A (3 replicates)
>> Level B (2 replicates)
>> Level C(1 replicate)
>> Level D(1 replicate)
>>
>> Can I legitimately calculate a P value for the contrast Level A to 
>> level C in the linear model even though I have only one replicate on 
>> Level C. I am not talking about just Limma here. I am talking about 
>> the linear model in general.
>
> Given assumption of common variance across levels, yes.
>
>>  Also,
>> I realize that one replicate is poor experimental design. This is 
>> what I was given to analyze.
>>
>> 2. If I wished to apply a multiple test correction to the pvalues 
>> from non-orthogonal contrasts, would the following procedure be 
>> legitimate::
>>
>>         1. Generate a pvalue for each contrast in the set of 
>> nonothogonal contrasts for each gene  using classifyTestsF().
>>         2. Correct the pvalues using a multiple test correction such 
>> as FDR.
>
> Nothing special about this design. All usual things, e.g. in limma, 
> apply.
>
> Gordon
>
>> I realize that no multiple-test correction is entirely satisfactory, 
>> I just want to get an approximate estimate of the p-values for each 
>> contrast as a guide to further experimentation and literature 
>> searching.
>>
>> 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/

In Memoriam, Francis Crick



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