What is the difference between the Fisher's Exact Test and Gene Set Enrichment Analysis?

 

Fisher’s Exact Test (Find Pathways/Groups Enriched with Selected Entities)

Fisher's exact test is a statistical test used to determine if there are nonrandom associations between two categorical variables.  (In Pathway Studio you run the Fisher’s Exact test from the command:  Find Pathways/Groups Enriched with Selected Entities).  You can use the Fisher’s Exact test to see if there are groups (such as ontology groups) or pathways that are statistically enriched in your list of genes.

For more information about the Fisher’s Exact test see:
http://mathworld.wolfram.com/FishersExactTest.html 

In gene expression analysis, the Fisher’s Exact test is typically run on the list of genes that have been determined (by fold change / p-value) to be statistically significantly differently expressed between experimental conditions.


Gene Set Enrichment Analysis

Gene Set Enrichment Analysis (GSEA) is similar to the Fisher’s Exact test in that it identifies statistical enrichment in experimental data of known groups (such as ontologies) and curated pathways.  Gene Set Enrichment analysis differs from Fisher’s Exact test in that the rank (based on experimental data values) of the genes in the experimental dataset is taken into consideration when identifying enrichment and the entire dataset can be used (no statistical threshold needs to be initially defined).

It is unnecessary to filter your data set by fold change/p-value before running the Gene Set Enrichment Analysis; however you can filter to remove genes with high p-values if desired.  (Recall the filters applied in Pathway Studio simply filter the view, but not the underlying data, and have no effect when used in the GSEA analysis.  If you run GSEA with the visual filter applied, the filter is ignored and GSEA is run on the complete underlying dataset.  If you want to run GSEA on a filtered subset of your data, you must import the subset as a separate experiment.)


Potential Advantages of Gene Set Enrichment over Fisher’s Exact Test:

  • Threshold relevance – In Fisher’s Exact test only the subset of genes determined by a relevance threshold is considered.  This list can be variable depending on the user defined chosen threshold (ex. fold change or p-value).
  • In the Fisher’s Exact Test the rank position of the gene in the experimental results is not considered (it is either on the list or its not).  In GSEA rank is considered.
  • GSEA is able to identify when many members of a pathway are changed even if none are changed above the threshold used in the Fisher’s Exact test (correlation).
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