[BioC] FC calculation in Limma

[Kasper Daniel Hansen]

If they are savvy I would explain that the log scale is the relevant
scale for analysis of microarrays and that they should therefore start
by log transforming.  A corollary to this is (of course) that fold
changes are calculated as they are.  I would explain that this has to
do with the distribution of noise in the intensity measurements.

If they are less savvy I would make an authoritative argument and
would say that this is how it has been done in the field in the last
10 years or more.

If this does not help, I would count myself lucky that they are not my
collaborators.  Of course, that does not help you.

Kasper

On Tue, Jan 18, 2011 at 9:20 PM, Lana Schaffer <schaffer at scripps.edu> wrote:
> Kasper,
> How do you tell customers that the fold-change is not the
> Average of X divided by the average Y signal?
> Lana
>
> -----Original Message-----
> From: Kasper Daniel Hansen [mailto:kasperdanielhansen at gmail.com]
> Sent: Tuesday, January 18, 2011 5:34 PM
> To: Lana Schaffer
> Cc: bioconductor at r-project.org
> Subject: Re: [BioC] FC calculation in Limma
>
> What is wrong with this?  Many papers have shown that (some) noise is
> additive on the log scale, so the relevant calculation should be
>  ave(log(X))
> Indeed, using log(ave(X)) goes against essentially the entire field of
> microarray analysis.  Of course, there might be special cases, but it
> seems you are making a general compliant.  So you need to come with
> some convincing references to convince me (us) that there is merit in
> your statement.
>
> (of course, I am not a limma author, so my opinion caries little weight).
>
> Kasper
>
> Postdoc, Department of Biostatistics, Johns Hopkins University
>
> On Tue, Jan 18, 2011 at 7:19 PM, Lana Schaffer <schaffer at scripps.edu> wrote:
>> Unfortunately, we have become aware recently that the FC calculation in Limma
>> Is not correct.  We input the expression values as log2 transformed values.  The
>> Average log expression value is then calculated by averaging the log values (ave(logX)).
>> However, this is NOT the log of the average expression value (logXbar) and so the reported
>> FC is therefore not correct.
>> Is there a possibility that the code can be corrected?
>>
>> Lana Schaffer
>> Biostatistics, Informatics
>> DNA Array Core Facility
>> 858-784-2263
>>
>>
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>>
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>