Depending on which counts number, the genes are overexpressed either up or down regulated in GSEA ?

Question

[Amr]

Depending on which counts number, the genes are overexpressed either up or down regulated in GSEA ? I mean what is the number of count (difference between normal and cancer cell) that when GSEA check it then decides if that gene set is over or down expressed ?

[jv]

From the GSEA paper (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1239896/) :

"Given an a priori defined set of genes S (e.g., genes encoding products in a metabolic pathway, located in the same cytogenetic band, or sharing the same GO category), the goal of GSEA is to determine whether the members of S are randomly distributed throughout L or primarily found at the top or bottom. We expect that sets related to the phenotypic distinction will tend to show the latter distribution."

The "standard" GSEA analysis doesn't look at gene counts. Instead it looks at a ranked list of genes.

There's a deeper discussion on this topic in another Biostars post https://www.biostars.org/p/132575/#132575.