[BioC] Limma

[Steve Lianoglou]

Howdy,

Just some thoughts:

On Wed, Apr 6, 2011 at 11:59 AM, James W. MacDonald
<jmacdon at med.umich.edu> wrote:
> Hi Seraya,
>
> On 4/6/2011 11:16 AM, Seraya Maouche wrote:
[snip]
> I think the reviewer's point is that you are computing a fold-change based
> on something that is primarily due to signal divided by something that is
> primarily due to noise. In other words, the numerator is signal, and the
> denominator is noise.
>
> In addition, the value due primarily to noise is very close to zero, so you
> end up with a huge fold change that can vary widely, depending on the
> variability of your noise signal. So the actual value of the ratio is
> probably not that meaningful, but the fact that it is reliably large
> probably means that the gene is truly differentially expressed. You just
> cannot say reliably by how much.

I don't know ... It's not entirely clear to me what is causing the
reviewer to be so upset about this.

Seraya, is there some assertion you are making regarding the actual
*value* of the fold change in these cases (where the denominator is
"absent"), or are you just saying that these (this) gene is
differentially express in cond_a vs. cond_b?

Anyway, in order to sidestep this "technicality", maybe one could put
the fold change into an "appropriate" scale after-the-fact?

For instance, in these situations where the gene is absent in one
expt, and not in the other, maybe one could set the expression of the
"absent" probes/genes in a given condition to be the minimum value of
a detected/expressed gene in that condition. Then calculate the fold
change post-facto? Where by post-facto I mean to just let limma do
"it's thing" without any data manipulation. Then, when Seraya is
listing some fold change value (in a table in the paper(?)), replace
the fold change of XX/0 (= Inf) with XX/(min gene expression in expt
the gene is absent in)?

I mean, the whole thing is a bit strange to me, unless you are indeed
asserting something based on the value of the fold change -- in which
case, the value itself in these situations I guess doesn't make much
sense at all and I reckon I can see the point the reviewer is
nitpicking over (?).

Just a thought,
-steve

-- 
Steve Lianoglou
Graduate Student: Computational Systems Biology
 | Memorial Sloan-Kettering Cancer Center
 | Weill Medical College of Cornell University
Contact Info: http://cbio.mskcc.org/~lianos/contact