Hello,
Apologies in advance if this post is too general for this forum.
I'm aware that the limma framework can be used for differential expression analysis at the pathway level with GSVA: https://www.bioconductor.org/packages/release/bioc/vignettes/GSVA/inst/doc/GSVA.html#72_Differential_expression_at_pathway_level
In essence, GSVA allows you to decompose your gene x sample expression matrix into a gene set x sample matrix, which can then be plugged into limma for DE testing.
My question is whether there is any problem with doing the same thing with module eigengenes? I.e. decompose your gene set x sample matrix into a module x sample matrix with the WGCNA workflow, and then use plug this into limma for, e.g: group A vs group B comparisons, associations with continuous variables etc.
In principal this seems fine to me, and seems like it would be more powerful than using lm() or lmer() with module eigengenes for such analyses, but I would be interested to hear any reservations.
Thank you
