In light of this we tried an alternative approach to identify aberrant driver TF activity by using a causal reasoning algorithm (Key Pathway Advisor) to identify upstream regulators that are responsible for influencing the changes in nuclear protein expression observed in AML (Table S5); however, these key hubs (the most significant of which was RNF4; Fig. S2) were also not predictive of the observed protein changes. This evidence concerns the gene RNF4 and acute myeloid leukemia.