Interpretation of "less" and "greater" after running gage with `same.dir = TRUE`

Question

[tmms]

Hello

I am having troubles interpreting the results after running gage, with same.dir = TRUE, on a log2 fold changes that were obtained after an analysis with DESeq2. I am not sure what the meaning of up- and downregualted pathways is. Are this pathways where all the genes are up- or downregulated? Additional, up- or downregulated compared to what?

I know that the sign of the log2 fold changes reflect in which condition the expression is up- or downregulated compared to chosen control. In my case, a positive log2 fold change corresponds to a gene that is more expressed in diseased cells compared to healthy cells, while a negative log2 fold change corresponds to a gene that is less expressed in diseased cells compared to healthy cells.

Thanks in advance.

[tmms]

After digging somewhat deeper, I found out that same.dir = TRUE performs a one-side two-sample t-test. The difference between "greater" (upregulated?) and "less" (downregulated?) is that first one calculates a p-value by using the right tail of the distribution while the second uses the left tail. I verified this by summing the p-values of the same pathway of greater and less. They sum to 1.

I am still not sure how to link such a result to the initial experiment.
Let's say I want to compare two groups: disease and control. I analyze the data in such a way that control is my reference group. Therefore, a positive log fold change corresponds to a gene that more expressed in the disease compared to the control and a negative log fold change corresponds to a gene that is less expressed in the diseases compared to the control.
Let's say I get a significant hit on a pathway in the "greater" category after running gage. This means that the mean log fold change in the gene set is larger than the overall mean log fold change.
So does this mean that the gene set is upregulated in the disease compared to the control?