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

[Erika Melissari]

Dear Jim,

thank you for your always usefull explanations.
If we observe a gene up-regulated in mutant "class" and also in the wt
"class" but the extent of this up-regulation is different and
statistically significant, we then should detect this gene as
differentially expressed in this contrast...is correct?


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

Yes, I know that if I increase the number of contrasts I need more degrees
of freedom to compute the statistics. I referred only to direct
comparison. If I have more samples and perform a large reference design
can I compute this interaction term the same?
thank you

Erika

> 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
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>




Erika Melissari