Tweaking Fisher’s exact test for biology

Fisher's exact test is widely applied in bioinformatics (it is the core computation in gene-set or pathway enrichment analysis).  I won't introduce the test itself as others have done it several times (here), but will rather point to a disconnect between what it does and what is often needed. In Fisher's exact test, the null hypothesis is that there is no enrichment between the two variables studied.  When using this test with large numbers (such as the number of genes [...]