Hi, I am using edgeR to analyze a knockout cell line vs WT control and expect a major fraction of transcripts differentially expressed. Using default settings with edgeR I could confirm significant downregulation of my knocked out transcript. However, given the following statement in the edgeR manual I am worried I am using incorrect assumptions for the analysis:
"TMM is recommended for most RNA-Seq data where the majority (more than half) of the genes are believed not differentially expressed between any pair of the samples. The following commands perform the TMM normalization and display the normalization factors."
What would be an acceptable strategy for data where most genes are believed to be differentially expressed?