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Weighted Pathways Analysis

I'm trying to do a pathways analysis/check for gene set enrichment on a list of genes. Right now I'm using DAVID, but that doesn't allow me to rank/weight my genes (i.e. give higher priority to genes that appear more often in my list). Does anyone know of a tool that allows you to do pathways analysis on a ranked list of genes?

gsea pathways analysis variant
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updated by Ram Ram • written by chloe.p.oconnell • chloe.p.oconnell

Why are genes appearing multiple times on your list? That's quite unusual.

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written by Devon Ryan Devon Ryan

It is a list of rare, high-impact variants. I converted the list of variants to a list of genes, and want to account for the fact that in my sample there are some genes that house a variant in 40% of my subjects and other genes that only house a variant in 2%.

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written by chloe.p.oconnell • chloe.p.oconnell

That makes a lot of sense then. One thing you might consider is the approach taken in this paper. In short, you could rank genes by a length-normalized number of significant high impact rare variants and then use GSEA to look at enrichment. Since I don't need to do this sort of thing normally, I expect others will chime in with other ideas.

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written by Devon Ryan Devon Ryan

I was under the impression that GSEA only does expression enrichment stuff and common variant stuff, and wasn't applicable to rare variant analysis. Correct me if I'm wrong.

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updated by Ram Ram • written by chloe.p.oconnell • chloe.p.oconnell

GSEA is really a generic rank-based enrichment method, so it could just as well be used in this case.

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written by Devon Ryan Devon Ryan

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