# Is there an established method for comparing expression of groups of genes (gene sets)?

I have a figure in a paper where I show the log2(fold-change) (obtained with DESeq2) between two groups (based on genotype) for genes within a specific hallmark gene set, and a reviewer is asking whether the differences are statistically significant.

I have not been able to find any methods for comparing expression of groups of genes like this, and i'm sure there is a method or a reason why it isn't done that I'm not aware of.

To be extra clear, what i have is two sets of log2FC values for a set of genes (one for one genotype (drug-treated vs. untreated) and the same for a second genotype), and I'm looking for a statistical comparison of these two groups of Log2FC measurements.

Thanks

• They want you to find genes whose response to the drug is different based on the genotype? If so, you can add an interaction term to your DESeq2 regression formula ~ condition + genotype + condition:genotype. Refer to the DESeq2 documentation and help("results", package="DESeq2") for more information on multifactor design and interaction terms. Sep 28 '20 at 14:26
• Okay yeah that makes sense for how to obtain differences in the response, but then how might I statistically compare these differences in response for a group of genes (I.e a gene set)? Would you just do something simple like a t test / Wilcox test? Sep 28 '20 at 14:58