Direction in GSEA in clusterProfiler

Question

[evcon]

Hi all,

Im doing GSEA with the clusterProfiler package in R, and I have a question about direction. When Ive done gsea on other platforms there was a column saying whether the gene set was "up" or "down." I don't see this in the gsearesult object. So if the gene set GSE23321_CENTRAL_MEMORY_VS_NAIVE_CD8_TCELL_DN is in the result is that saying genes that are down regulated in memory t-cells vs naive are upregulated in mine or also down regulated?

Thanks!

[young_bioinformatician]

It is a bit complex to explain enrichment as up/down and neutral. I would say that the genes you have are positively / negatively enriched in up-regulated direction and/or exact opposite for down-regulated genes.

In fact, I have tried to cope with pathway enrichment issue before and our team could not solve it how we should exactly interpret the result.

Answer 1

[kand3e]

You have to check the sign of your ES/NES. Positive sign means enrichment of genes that are located near the top of your list (which should be pre-ranked), and negative sign means enrichment of genes located near the bottom of your list.

Answer 2

[Danielle B]

Hi Evcon,

I think the "DN" in the gene set you are talking about is unrelated to your own data set. If this GSE23321 gene set showed up in your GSEA results with a positive ES/NES value, then it generally means that your up-regulated genes in your first comparison group are enriched in the GSE23321 gene set (depending on the FDR values, etc)). Conversely, if this GSE23321 gene set showed up in your GSEA result file with negative ES/NES values, then it suggests your down-regulated genes are enriched in this data set. The "DN" mentioned in the gene set name is only referring to the results of another study, which you can read about here: https://www.gsea-msigdb.org/gsea/msigdb/cards/GSE23321_CENTRAL_MEMORY_VS_NAIVE_CD8_TCELL_DN

It definitely gets confusing, feel free to reach back out if you have more questions!

Best, Danielle