Hi guys I have a quite conceptual question on the significance of the comparison between two lists of genes. I have list1 and list2. Both lists contain 100 genes. The overlap is 13 genes and the universe is 17,611 genes (is the full set of genes from which the lists of 100 genes were derived). If I perform the Fisher's exact test to calculate the p-value of the overlap, i.e. the significance, it is p < 1.351e-14. It is strongly significant and I understand why if I consider the length of the universe. But if we consider the lists of 100 genes, the overlap is quite low: 13%. Should I consider the overlap finally significant or not?

Thank you in advance

You can also simply take two random sets of 100 genes from 17,611 universal set and check how often you observe an overlap of 13 or more. This gives a sense to you if 13 gene overlapping is not by chance.

You can do 1000 random sets of 100 genes and check how ofter there is an overlap of 13 or more genes.

Fishers test is doing something similar but by doing random sets, you get a better sense.