What does it mean in GSEA when HALLMARK_UV_RESPONSE_DN is upregulated ? how it's down and upregulated?

Question

[Amr]

What does it mean in GSEA when HALLMARK_UV_KRAS_SIGNALING_DN is upregulated ? how it's down and upregulated?

Answer 1

[Papyrus]

You can check info about the pathways here (e.g. this one) and typically links to original sources. So, if, in your system, "UV_RESPONSE_DN" genes are up-regulated, it means that "genes which go down in response to UV light as defined in some literature studies, appear to go up in your study".

[jv]

True, but may not necessarily be the case here. Some gene set enrichment tools will calculate "negative" enrichment, i.e. enrichment within downregulated or lower expressed genes. OP did not provide sufficient details about the method that was used that would help to interpret these results.

[Papyrus]

Well, they did state their pathway was "upregulated" in GSEA, not "enriched", so I assume that they meant is was enriched with a positive enrichment score in GSEA.

We can hypothesize that they meant to say "enriched" instead of "upregulated" so the question would be very different and, indeed, then we would have to explain that GSEA outputs both "upregulated" (positive) and "downregulated" (negative) enrichment scores.

Nonetheless I agree the question is scarce on details ;) (and the title pathway does not agree with the text)

[Amr]

Yes I mean positively enriched (upregulated), so in a cancer sample if HALLMARK_UV_RESPONSE_UP and HALLMARK_UV_RESPONSE_DN both were upregulated it means that genes that are upregulated by the UV and genes that are downregulated by UV both are upregulated in my sample? right?

[Papyrus]

Yep. Whether that makes sense in your study system is up to you. Also, gene set enrichment is far from being an exact science and provides mostly descriptive results to guide your research.

[Amr]

Thanks a lot :)