text: user39: 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
  
  user48: You could apply the GSVA transformation to later compare them. You would need to give a step back and start from the expression values not log2FC, but I think it would be better than using the log2FC directly.
  If you need to use them you could compare the gene set enrichment value of these two sets on the same comparison. I would use fgsea with the log2FC and the two sets of genes. If the normalized enrichment value (NES) is different then you could explain that these sets expression are indeed different.
  
original_text: 39: <p>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.</p>
  <p>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.</p>
  <p>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.</p>
  <p>Thanks</p>
   48: <p>You could apply the <a href="https://bioconductor.org/packages/GSVA" rel="nofollow noreferrer">GSVA</a> transformation to later compare them. You would need to give a step back and start from the expression values not log2FC, but I think it would be better than using the log2FC directly.</p>
  <p>If you need to use them you could compare the gene set enrichment value of these two sets on the same comparison. I would use <a href="https://bioconductor.org/packages/fgsea" rel="nofollow noreferrer">fgsea</a> with the log2FC and the two sets of genes. If the normalized enrichment value (NES) is different then you could explain that these sets expression are indeed different.</p>
  