understanding the GS details output

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N Sahgal

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Dec 20, 2021, 9:28:55 AM12/20/21
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Hello Anthony,

I am interested in a specific geneset after running the pre-rankned GSEA mode on RNA-Seq data, using go-cc and gene id as other inputs.

I increased the plots, size so that it could give me details of geneset of interest.

I have the following questions on trying to understand and interpret the output in GS details:
1) in the enrichment plot, what does it mean if there are two peaks, one at the pos and the other at the neg? i.e. looks like a sine wave

2) How does one truly interpret the table, below the enrichment plot which shows genes in the geneset?

I thought that the Core enrichment = YES, are the genes that are responsible for the geneset being enriched, implying these genes would be of interest rather than the 'No' genes to validate or investigate.
I, also thought that the running ES would reduce from the point in states 'No', but that doesn't appear to be the case. 

I'm therefore, not sure how one interprets this, and would appreciate any insights and suggestions.

Many Thanks,
NSahgal


Anthony Castanza

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Dec 20, 2021, 1:11:15 PM12/20/21
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Hi NSahgal,

Two peaks on opposite sides of the graph typically indicates that there is a substantial number of genes in the set that are regulated oppositely. GSEA only looks for coordinated changes, so a gene set that contains genes that are substantially up AND substantially down will likely (effectively) cancel out. GSEA does have an absolute value mode, it might be helpful here if such oppositely regulated components are both expected and of interest, but I can't really speak to the results of it.

The genes marked "yes" in the results stable represent the "core enrichment" genes, these are the genes that represent the maximum deviation from zero when calculating the running enrichment score. These typically represent the strongest driving force to an observed enrichment result. The "Running ES" should start reducing after those genes. If this is not what you're seeing, then a screenshot of the specific result might be helpful for interpretation.

-Anthony

Anthony S. Castanza, PhD
Curator, Molecular Signatures Database
Mesirov Lab, Department of Medicine
University of California, San Diego

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