Why DE genes are not among highly variable genes between groups

Question

[Björn]

I got list of "highly variable genes" between Groups A x B using variance in edgeR (ref: highly variable genes) Then performed standard edgeR analysis to find DE genes. ref: edgeR

PROBLEM: Why none of the DE genes between A x B are included in "highly variable genes"

My questions 1. What is the reason for the problem ? 2. Considering the problem, what is the use of "highly variable genes" in publication ? Can I simply exclude it and go with DE gene analysis only.

[Martombo]

did you determine your "highly variable genes" as it is indicated in your first reference? If so, these are not highly variable genes between groups A and B, as you call them, but rather genes with the highest variance in your data. That means they can change a lot independently of the group. For this reason you shouldn't expect an overlap with your AvsB DEGs.

Answer 1

[Devon Ryan]

Highly variable genes are useful for clustering samples and seeing if you've done things like swapped a sample label or have outlier samples. One should not expect them to be differentially expressed. You're looking at a quality control step, how you proceed will depend entirely on what it looks like.