[BioC] Interspecies differential expression of orthologs with Edger

[Steve Lianoglou]

Hi,

On Mon, Sep 8, 2014 at 1:41 PM, assaf www <assafwww at gmail.com> wrote:
> Hi Steve
>
> I will look into limma::voom (was not aware of this approach).

This is "just" another approach to do differential expression analysis
with rna-seq data -- ie. one could use edgeR, DESeq2, limma::voom,
etc. to do "standard" differential expression (count) testing.

> Do you mean GO enrichment (e.g., David/Go-seq/etc), is so then no, its not
> what I mean.

No, I do not mean GO enrichment, I really meant "gene set enrichment
analysis", it's "a thing" ... look at the help and references listed
under ?camera and ?roast, I thought your motivation to group
"features" together was to do something along those lines but from
what you say below, it seems not (?)

> I specifically would like to ask if Edger (or similar tools) could give
> reasonable DE estimation by comparing the sum of counts of groups of genes
> (instead single genes).

It's not clear to me what "reasonable" means in this case, to be honest.

> This is a completely different thing - it may possibly allow working-around
> the issue of paralogy-orthology when performing cross-species DE analysis,
> and may have multiple other advantages I believe (regardless of
> cross-species things).
> (Of course, in case it doesn't violate the basic assumptions of these DE
> analyzes, and can keep the data properly normalized - this is my question)

Without getting too involved here, my gut feeling is that going about
things in this way is making things worse ... not better.

I'm not sure where to start pointing you for some help, and this might
be entirely unrelated (but I'll let you figure that one out ;-), but
maybe you can take a look at the paper written by the DEXSeq folks:

Drift and conservation of differential exon usage across tissues in
primate species
http://www.pnas.org/content/110/38/15377.short

I admit that this isn't directly doing what you are doing, but perhaps
they touch upon some issues that might be of help to you ... to be
honest, however, I haven't given it a good read through, even though
it has been on my "readme" list for sometime (over a year,
apparently!).

-steve

-- 
Steve Lianoglou
Computational Biologist
Genentech