[BioC] interaction term contrast in Weaver mutant example of LIMMA manual

[James W. MacDonald]

Hi Erika,

Erika Melissari wrote:
> Dear bioconductor list,
> 
> I am studing the Weaver experiment example of LIMMA manual and I am in a
> maze about the biological meaning of interaction term present among the
> contrasts.
> I did not manage to understend what kind of differentially expressed gene
> this contrast takes-out.

In this experiment we can look at genes that change between the two time 
points in the mutant samples, or that change between the two time points 
in the wild type samples. In addition, we might be interested in those 
genes that react differently in the two sample types. In other words, a 
particular gene might increase expression in the wild type samples, but 
actually decrease expression in the mutant samples.

This third comparison is known as an interaction.

> The interaction contrast is:
> 
> (P21mt-P11mt)-(P21wt-P11wt)

Correct. So using our example from above, the first term will be 
negative (since the expression level went down in mutant samples). The 
second term will be positive, since the expression went up over time in 
the wild type samples, but since we subtract, we end up with a 
(possibly) large negative number.

The same will be true of any scenario you can envision where the mutant 
and wild type samples react differently to the incubation time. Another 
example would be the situation where the mutant samples were 
up-regulated at 21 hours, but the wild type samples were unaffected. In 
this case you can see that we might have a large value for this contrast.

However, if both wild type and mutant samples were up-regulated 
approximately the same amount, the resulting value would be very close 
to zero.

> 
> The first bracket takes-out the differentially expressed genes between the
> mutant subjects at two different time points(21 and 11 minutes) and the
> second bracket those between the wild-type subject at the same different
> time points.
> ..but what differentially expressed genes takes-out the global interaction
> contrast?
> 
> In order to evaluate an interaction do I need absolutely the four arrays
> in direct comparison done in this example?

Not four arrays, but four treatment/sample combinations. You will need 
replication to compute this contrast.

Best,

Jim


> 
> Thank you very much for any explaination
> 
> Erika
> 
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-- 
James W. MacDonald, M.S.
Biostatistician
Douglas Lab
University of Michigan
Department of Human Genetics
5912 Buhl
1241 E. Catherine St.
Ann Arbor MI 48109-5618
734-615-7826