clusterProfiler GSEA for upregulated and downregulated gene sets: conflicting results

I'm using GSEA function to perform enrichment analysis on my pre-ranked gene list. The function takes only genes sorted in decreasing order by a metric of choice, so I've ordered genes by decreasing DESeq2 test statistics, which reflects direction and significance of change.

When I revert the order of genes (by changing a reference condition during DESeq2 testing or just by multiplying DESeq2 statistics by -1) I get substantially different GSEA results. Is this behaviour expected?. If so, Can I perform separate tests for sets enriched in each condition? (I think the desktop version of GSEA does that by default.)


GSEA


clusterProfiler


DESeq2

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updated 2 hours ago by

Hannes

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