There are other biases that might affect gene set analysis results including annotation biases from different databases. Two examples are: 1) genes that have been well studied are more thoroughly annotated; and 2) there may be discrepancies of gene set definitions in different databases (e.g., KEGG [20] vs. BioCyc [50]). Furthermore, for enrichment based methods that test the competitive null hypothesis, the choice of the background genes for the enrichment test is a critical factor and a potential bias.