Gene set enrichment analysis

Question

[Shamim Sarhadi]

Hi I run GSEA on a pre-ranked (according to the log fold changes values) gene list that obtained from a DEG analysis between healthy and cancer samples, after GSEA I used significant geneset for leading edge analysis, but the result is ambiguous !! I attached one of leading edge clustergrams here As you see for example there are some up-regulated genes in cell_cycle gene set but I expected the presence of some down-regulated genes related with cell cycle. I think there is a misunderstanding about GSEA result. Could you please explain for me

Thanks in advance

[Kevin Blighe]

GSEA is often ambiguous because many terms and pathways are general. 'Cell cycle' is possibly one of the most general terms that exists.

Assuming that your colour shading is based on fold-changes: In your specific example, if the genes that you're plotting have positive fold-changes coupled with statistically significant P values, then they should appear as up-regulated; if these genes have negative fold-changes, then they should appear as down-regulated.

Be sure of what you are actually plotting in the figure.