Figure 1.

The complement and coagulation cascade as affected by treatment with palmitate in a hepatic cell line. There are seven differentially expressed genes (red, up-regulated; blue, down-regulated) out of 69 total genes. All classical ORA models would give any other pathway with the same proportion of genes a similar P-value, disregarding the fact that six out of these seven genes are involved in the same region of the pathway, closely interacting with each other. Both ORA and GSEA would yield exactly the same significance value to this pathway even if the diagram were to be completely redesigned by future discoveries. In contrast, the impact factor can distinguish between this pathway and any other pathway with the same proportion of differentially expressed gene, as well as take into account any future changes to the topology of the pathway.