Table 3. Top 15 significant upstream transcription regulators.

Upstream Regulator	Log Ratio	Activation z-score#	P-value of overlap&
Inhibition
TP53		−2.353	3.34×10−32
NUPR1	−2.52	−3.977	4.62×10−13
NKX2-3		−3.455	5.88×10−12
HNF1A		−2.359	8.82×10−12
CDKN2A	1.737	−3.219	1.34×10−11
estrogen receptor		−2.299	9.57×10−10
RB1		−4.286	3.74×10−08
TCF3		−3.116	4.32×10−08
TRIM24		−3.714	6.26×10−07
BCL6		−2.313	1.60×10−06
NR5A2	−2.876	−2.7	7.26×10−06
SATB1	−0.814	−2.003	1.09×10−05
IRF4	2.115	−2.41	4.24×10−05
RBL1		−3.124	1.72×10−04
SPDEF		−2.887	2.39×10−04
Activation
STAT3		2.924	5.78×10−19
CTNNB1		3.359	1.99×10−15
SP1		2.06	4.79×10−13
CEBPB		2.866	2.62×10−12
NFkB (complex)		6.314	1.43×10−11
TBX2		4.99	1.62×10−11
IRF1		3.759	2.76×10−11
IRF7	1.504	5.591	2.88×10−10
FOXM1	2.152	4.395	5.12×10−10
STAT1		4.576	2.05×10−08
ETS1	0.863	2.575	5.06×10−08
JUN		2.045	5.57×10−08
FOXO1		3.242	9.35×10−08
E2F3	1.137	2.394	1.16×10−06
MBD2		2.549	5.41×10−06

^#Activation z-score is a statistical parameter that determines whether an upstream transcription regulator has significantly more “activated” predictions than “inhibited” predictions (z>0) or vice versa (z<0). Here, significance means that we reject the hypothesis that predictions are random with equal probability.

^&Overlap P-value measures whether there is a statistically significant overlap between the dataset genes and the genes that are regulated by a transcriptional regulator. It is calculated using Fisher's Exact Test, and significance is generally attributed to P-values < 0.01. Since the regulation direction (“activating” or “inhibiting”) of an edge is not taken into account for the computation of overlap P-values the underlying network also includes findings without associated directional attribute, such as protein-DNA (promoter) binding.