PARADIGM pathway analysis of mRNA expression data - Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Signaling events mediated by Stem cell factor receptor (c-Kit)	26
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	20
Fc-epsilon receptor I signaling in mast cells	19
Arf6 signaling events	16
FOXM1 transcription factor network	12
IGF1 pathway	11
Thromboxane A2 receptor signaling	10
Endothelins	9
Glucocorticoid receptor regulatory network	8
S1P1 pathway	8

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.4815	26	2065	78	-1.1	0.36	1000	-1000	-0.034	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.3704	20	1382	68	-1.2	0.69	1000	-1000	-0.066	-1000
Fc-epsilon receptor I signaling in mast cells	0.3519	19	1915	97	-0.68	0.075	1000	-1000	-0.075	-1000
Arf6 signaling events	0.2963	16	1042	62	-0.68	0.034	1000	-1000	-0.032	-1000
FOXM1 transcription factor network	0.2222	12	639	51	-1	0.016	1000	-1000	-0.099	-1000
IGF1 pathway	0.2037	11	645	57	-0.41	0.086	1000	-1000	-0.066	-1000
Thromboxane A2 receptor signaling	0.1852	10	1064	105	-0.28	0.087	1000	-1000	-0.048	-1000
Endothelins	0.1667	9	934	96	-0.61	0.043	1000	-1000	-0.053	-1000
Glucocorticoid receptor regulatory network	0.1481	8	1012	114	-1.2	0.37	1000	-1000	-0.046	-1000
S1P1 pathway	0.1481	8	310	36	-0.45	0.018	1000	-1000	-0.056	-1000
EGFR-dependent Endothelin signaling events	0.1481	8	175	21	-0.18	0.023	1000	-1000	-0.043	-1000
HIF-1-alpha transcription factor network	0.1296	7	588	76	-0.63	0.026	1000	-1000	-0.045	-1000
IL4-mediated signaling events	0.1296	7	640	91	-0.97	0.44	1000	-1000	-0.085	-1000
FAS signaling pathway (CD95)	0.1296	7	365	47	-0.34	0.095	1000	-1000	-0.025	-1000
Ephrin B reverse signaling	0.1111	6	311	48	-0.19	0.022	1000	-1000	-0.051	-1000
Nongenotropic Androgen signaling	0.1111	6	316	52	-0.36	0.16	1000	-1000	-0.043	-1000
FOXA2 and FOXA3 transcription factor networks	0.0926	5	268	46	-0.79	0.17	1000	-1000	-0.012	-1000
PDGFR-alpha signaling pathway	0.0926	5	263	44	-0.51	0.036	1000	-1000	-0.057	-1000
Integrins in angiogenesis	0.0926	5	444	84	-0.48	0.04	1000	-1000	-0.065	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0926	5	747	125	-0.51	0.023	1000	-1000	-0.071	-1000
IL23-mediated signaling events	0.0926	5	303	60	-0.35	0.022	1000	-1000	-0.087	-1000
Signaling events mediated by PRL	0.0926	5	170	34	-0.25	0.023	1000	-1000	-0.012	-1000
Ras signaling in the CD4+ TCR pathway	0.0926	5	86	17	-0.13	0.015	1000	-1000	-0.025	-1000
Signaling events mediated by the Hedgehog family	0.0741	4	215	52	-0.53	0.32	1000	-1000	-0.016	-1000
Glypican 1 network	0.0741	4	231	48	-0.48	0.043	1000	-1000	-0.017	-1000
Insulin Pathway	0.0741	4	329	74	-0.48	0.051	1000	-1000	-0.065	-1000
Regulation of nuclear SMAD2/3 signaling	0.0556	3	462	136	-0.62	0.11	1000	-1000	-0.037	-1000
IL12-mediated signaling events	0.0556	3	318	87	-0.56	0.04	1000	-1000	-0.076	-1000
PLK2 and PLK4 events	0.0556	3	10	3	-0.05	-0.006	1000	-1000	-0.013	-1000
BMP receptor signaling	0.0556	3	250	81	-0.44	0.038	1000	-1000	-0.075	-1000
amb2 Integrin signaling	0.0556	3	304	82	-0.46	0.05	1000	-1000	-0.062	-1000
Ceramide signaling pathway	0.0556	3	256	76	-0.26	0.073	1000	-1000	-0.025	-1000
TCGA08_retinoblastoma	0.0556	3	31	8	-0.045	0.021	1000	-1000	-0.005	-1000
BCR signaling pathway	0.0556	3	356	99	-0.21	0.064	1000	-1000	-0.069	-1000
Plasma membrane estrogen receptor signaling	0.0556	3	279	86	-0.26	0.058	1000	-1000	-0.056	-1000
Caspase cascade in apoptosis	0.0370	2	160	74	-0.11	0.045	1000	-1000	-0.021	-1000
Signaling events mediated by HDAC Class II	0.0370	2	193	75	-0.49	0.038	1000	-1000	-0.035	-1000
ErbB4 signaling events	0.0370	2	138	69	-0.39	0.058	1000	-1000	-0.063	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0370	2	75	28	-0.39	0.027	1000	-1000	-0.014	-1000
Signaling events mediated by PTP1B	0.0370	2	178	76	-0.44	0.043	1000	-1000	-0.055	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0370	2	80	37	-0.18	0.039	1000	-1000	-0.035	-1000
TRAIL signaling pathway	0.0370	2	126	48	-0.063	0.023	1000	-1000	-0.045	-1000
IL1-mediated signaling events	0.0370	2	174	62	-0.19	0.073	1000	-1000	-0.06	-1000
Signaling events regulated by Ret tyrosine kinase	0.0370	2	176	82	-0.43	0.03	1000	-1000	-0.067	-1000
FoxO family signaling	0.0370	2	167	64	-0.52	0.085	1000	-1000	-0.038	-1000
IL2 signaling events mediated by PI3K	0.0370	2	139	58	-0.39	0.039	1000	-1000	-0.062	-1000
Regulation of p38-alpha and p38-beta	0.0370	2	114	54	-0.46	0.042	1000	-1000	-0.042	-1000
IL27-mediated signaling events	0.0370	2	126	51	-1.1	0.37	1000	-1000	-0.061	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0370	2	204	88	-0.67	0.075	1000	-1000	-0.068	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0370	2	298	120	-0.56	0.18	1000	-1000	-0.059	-1000
Regulation of Androgen receptor activity	0.0370	2	145	70	-0.49	0.067	1000	-1000	-0.05	-1000
Coregulation of Androgen receptor activity	0.0185	1	88	76	-0.087	0.026	1000	-1000	-0.032	-1000
Osteopontin-mediated events	0.0185	1	42	38	-0.32	0.06	1000	-1000	-0.059	-1000
Syndecan-2-mediated signaling events	0.0185	1	130	69	-0.53	0.041	1000	-1000	-0.014	-1000
Cellular roles of Anthrax toxin	0.0185	1	70	39	-0.1	0.017	1000	-1000	-0.023	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0185	1	111	85	-0.32	0.063	1000	-1000	-0.055	-1000
Presenilin action in Notch and Wnt signaling	0.0185	1	97	61	-0.32	0.049	1000	-1000	-0.055	-1000
p75(NTR)-mediated signaling	0.0185	1	196	125	-0.32	0.055	1000	-1000	-0.067	-1000
EPO signaling pathway	0.0185	1	98	55	-0.22	0.042	1000	-1000	-0.061	-1000
mTOR signaling pathway	0.0185	1	91	53	-0.041	0.039	1000	-1000	-0.051	-1000
IFN-gamma pathway	0.0185	1	68	68	-0.087	0.071	1000	-1000	-0.073	-1000
Nectin adhesion pathway	0.0185	1	83	63	-0.034	0.045	1000	-1000	-0.055	-1000
ceramide signaling pathway	0.0185	1	58	49	-0.19	0.051	1000	-1000	-0.03	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0185	1	103	52	-0.49	0.077	1000	-1000	-0.033	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0185	1	86	83	-0.19	0.067	1000	-1000	-0.051	-1000
Syndecan-3-mediated signaling events	0.0185	1	61	35	-0.28	0.038	1000	-1000	-0.032	-1000
Signaling mediated by p38-alpha and p38-beta	0.0185	1	68	44	-0.076	0.036	1000	-1000	-0.037	-1000
TCR signaling in naïve CD8+ T cells	0.0185	1	131	93	-0.076	0.046	1000	-1000	-0.058	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0185	1	72	45	-0.073	0.044	1000	-1000	-0.065	-1000
EPHB forward signaling	0.0185	1	116	85	-0.05	0.043	1000	-1000	-0.064	-1000
Calcium signaling in the CD4+ TCR pathway	0.0185	1	49	31	-0.32	0.035	1000	-1000	-0.045	-1000
LPA receptor mediated events	0.0185	1	118	102	-0.32	0.051	1000	-1000	-0.055	-1000
IL6-mediated signaling events	0.0185	1	138	75	-0.32	0.091	1000	-1000	-0.046	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0185	1	144	74	-0.26	0.079	1000	-1000	-0.064	-1000
IL2 signaling events mediated by STAT5	0.0185	1	23	22	-0.045	0.086	1000	-1000	-0.01	-1000
Class I PI3K signaling events	0.0185	1	127	73	-0.17	0.06	1000	-1000	-0.038	-1000
Arf6 trafficking events	0.0185	1	91	71	-0.27	0.049	1000	-1000	-0.048	-1000
Regulation of Telomerase	0.0185	1	119	102	-0.32	0.061	1000	-1000	-0.081	-1000
Syndecan-4-mediated signaling events	0.0185	1	125	67	-0.62	0.049	1000	-1000	-0.077	-1000
VEGFR1 specific signals	0.0185	1	88	56	-0.51	0.061	1000	-1000	-0.022	-1000
S1P3 pathway	0.0185	1	58	42	-0.39	0.033	1000	-1000	-0.018	-1000
Visual signal transduction: Rods	0.0185	1	97	52	-0.28	0.043	1000	-1000	-0.057	-1000
E-cadherin signaling in keratinocytes	0.0185	1	53	43	-0.066	0.047	1000	-1000	-0.048	-1000
LPA4-mediated signaling events	0.0000	0	3	12	-0.004	0.032	1000	-1000	-0.012	-1000
ErbB2/ErbB3 signaling events	0.0000	0	56	65	-0.18	0.049	1000	-1000	-0.051	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	7	23	-0.011	0.048	1000	-1000	-0.029	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0000	0	4	34	-0.024	0.046	1000	-1000	-0.015	-1000
Canonical NF-kappaB pathway	0.0000	0	2	39	0	0.096	1000	-1000	-0.06	-1000
BARD1 signaling events	0.0000	0	1	57	-0.066	0.046	1000	-1000	-0.045	-1000
Syndecan-1-mediated signaling events	0.0000	0	10	34	-0.12	0.019	1000	-1000	-0.017	-1000
Visual signal transduction: Cones	0.0000	0	10	38	-0.004	0.042	1000	-1000	-0.043	-1000
Circadian rhythm pathway	0.0000	0	3	22	-0.063	0.049	1000	-1000	-0.029	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0000	0	9	54	-0.051	0.046	1000	-1000	-0.067	-1000
Ephrin A reverse signaling	0.0000	0	0	7	0	0.029	1000	-1000	-0.01	-1000
JNK signaling in the CD4+ TCR pathway	0.0000	0	12	17	-0.037	0.041	1000	-1000	-0.015	-1000
Noncanonical Wnt signaling pathway	0.0000	0	2	26	-0.015	0.05	1000	-1000	-0.03	-1000
a4b1 and a4b7 Integrin signaling	0.0000	0	0	5	0.013	0.021	1000	-1000	-0.01	-1000
Hedgehog signaling events mediated by Gli proteins	0.0000	0	40	65	-0.11	0.06	1000	-1000	-0.043	-1000
Aurora A signaling	0.0000	0	4	60	-0.12	0.042	1000	-1000	-0.016	-1000
Arf6 downstream pathway	0.0000	0	0	43	-0.037	0.038	1000	-1000	-0.023	-1000
Aurora C signaling	0.0000	0	0	7	-0.021	0.016	1000	-1000	-0.029	-1000
PLK1 signaling events	0.0000	0	2	85	-0.11	0.034	1000	-1000	-0.041	-1000
Insulin-mediated glucose transport	0.0000	0	30	32	-0.074	0.035	1000	-1000	-0.032	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	64	68	-0.13	0.067	1000	-1000	-0.039	-1000
Signaling events mediated by HDAC Class III	0.0000	0	6	40	-0.024	0.026	1000	-1000	-0.034	-1000
Reelin signaling pathway	0.0000	0	18	56	-0.051	0.047	1000	-1000	-0.051	-1000
S1P5 pathway	0.0000	0	12	17	-0.024	0.017	1000	-1000	-0.014	-1000
HIF-2-alpha transcription factor network	0.0000	0	28	43	-0.14	0.15	1000	-1000	-0.058	-1000
Signaling events mediated by HDAC Class I	0.0000	0	49	104	-0.23	0.059	1000	-1000	-0.048	-1000
TCGA08_p53	0.0000	0	0	7	-0.031	0.023	1000	-1000	-0.012	-1000
Signaling mediated by p38-gamma and p38-delta	0.0000	0	2	15	0	0.026	1000	-1000	-0.016	-1000
Retinoic acid receptors-mediated signaling	0.0000	0	37	58	-0.064	0.049	1000	-1000	-0.054	-1000
Paxillin-dependent events mediated by a4b1	0.0000	0	35	36	-0.18	0.046	1000	-1000	-0.047	-1000
Atypical NF-kappaB pathway	0.0000	0	7	31	0	0.055	1000	-1000	-0.012	-1000
Canonical Wnt signaling pathway	0.0000	0	16	51	-0.082	0.071	1000	-1000	-0.04	-1000
Effects of Botulinum toxin	0.0000	0	2	26	-0.002	0.032	1000	-1000	-0.041	-1000
Glypican 2 network	0.0000	0	0	4	-0.042	0	1000	-1000	-0.01	-1000
Wnt signaling	0.0000	0	2	7	-0.015	0.017	1000	-1000	-0.016	-1000
TCGA08_rtk_signaling	0.0000	0	23	26	-0.066	0.052	1000	-1000	-0.013	-1000
E-cadherin signaling in the nascent adherens junction	0.0000	0	39	76	-0.024	0.052	1000	-1000	-0.06	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.039	1000	-1000	-0.04	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0000	0	0	33	-0.051	0.049	1000	-1000	-0.014	-1000
Rapid glucocorticoid signaling	0.0000	0	1	20	0	0.021	1000	-1000	-0.012	-1000
PDGFR-beta signaling pathway	0.0000	0	57	97	-0.39	0.047	1000	-1000	-0.062	-1000
Class IB PI3K non-lipid kinase events	0.0000	0	0	3	-0.015	0.016	1000	-1000	-0.003	-1000
S1P4 pathway	0.0000	0	15	25	-0.024	0.027	1000	-1000	-0.014	-1000
E-cadherin signaling events	0.0000	0	3	5	0.002	0.023	1000	-1000	-0.007	-1000
p38 MAPK signaling pathway	0.0000	0	20	44	-0.014	0.036	1000	-1000	-0.059	-1000
Arf1 pathway	0.0000	0	0	54	-0.001	0.04	1000	-1000	-0.026	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.046	1000	-1000	-0.01	-1000
Aurora B signaling	0.0000	0	60	67	-0.18	0.016	1000	-1000	-0.054	-1000
Total	NA	318	24908	7203	-35	8.6	131000	-131000	-5.5	-131000

Signaling events mediated by Stem cell factor receptor (c-Kit)

Figure S1. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S1. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.32	0.17	-10000	0	-0.39	45	45
CRKL	-0.34	0.18	-10000	0	-0.42	45	45
HRAS	-0.26	0.15	-10000	0	-0.37	15	15
mol:PIP3	-0.33	0.16	-10000	0	-0.4	44	44
SPRED1	0.002	0.095	-10000	0	-0.69	1	1
SPRED2	0.016	0	-10000	0	-10000	0	0
GAB1	-0.37	0.19	-10000	0	-0.45	45	45
FOXO3	-0.31	0.16	-10000	0	-0.38	45	45
AKT1	-0.34	0.17	-10000	0	-0.41	45	45
BAD	-0.32	0.16	-10000	0	-0.38	45	45
megakaryocyte differentiation	-0.36	0.18	-10000	0	-0.43	45	45
GSK3B	-0.31	0.16	-10000	0	-0.38	45	45
RAF1	-0.21	0.13	-10000	0	-0.35	4	4
SHC1	0.016	0	-10000	0	-10000	0	0
STAT3	-0.36	0.18	-10000	0	-0.44	45	45
STAT1	-0.88	0.44	-10000	0	-1.1	46	46
HRAS/SPRED1	-0.22	0.13	-10000	0	-0.4	4	4
cell proliferation	-0.36	0.18	-10000	0	-0.43	45	45
PIK3CA	0.002	0.095	-10000	0	-0.69	1	1
TEC	0.013	0.022	-10000	0	-10000	0	0
RPS6KB1	-0.36	0.18	-10000	0	-0.44	45	45
HRAS/SPRED2	-0.21	0.13	-10000	0	-0.41	2	2
LYN/TEC/p62DOK	-0.33	0.17	-10000	0	-0.4	45	45
MAPK3	-0.15	0.097	-10000	0	-0.28	2	2
STAP1	-0.36	0.18	-10000	0	-0.44	45	45
GRAP2	0.016	0	-10000	0	-10000	0	0
JAK2	-0.72	0.35	-10000	0	-0.86	46	46
STAT1 (dimer)	-0.86	0.43	-10000	0	-1	46	46
mol:Gleevec	0.013	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.34	0.18	-10000	0	-0.41	45	45
actin filament polymerization	-0.36	0.18	-10000	0	-0.44	45	45
LYN	0.013	0.022	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.5	0.24	-10000	0	-0.6	45	45
PIK3R1	0.002	0.095	-10000	0	-0.69	1	1
CBL/CRKL/GRB2	-0.3	0.16	-10000	0	-0.37	45	45
PI3K	-0.35	0.19	-10000	0	-0.42	45	45
PTEN	0.003	0.095	-10000	0	-0.69	1	1
SCF/KIT/EPO/EPOR	-1	0.5	-10000	0	-1.2	45	45
MAPK8	-0.36	0.18	-10000	0	-0.44	45	45
STAT3 (dimer)	-0.36	0.18	-10000	0	-0.43	45	45
positive regulation of transcription	-0.12	0.082	-10000	0	-0.23	2	2
mol:GDP	-0.28	0.16	-10000	0	-0.38	18	18
PIK3C2B	-0.37	0.19	-10000	0	-0.45	45	45
CBL/CRKL	-0.32	0.17	-10000	0	-0.39	45	45
FER	-0.36	0.18	-10000	0	-0.44	45	45
SH2B3	-0.36	0.18	-10000	0	-0.44	45	45
PDPK1	-0.3	0.15	-10000	0	-0.37	44	44
SNAI2	-0.45	0.23	-10000	0	-0.51	48	48
positive regulation of cell proliferation	-0.62	0.3	-10000	0	-0.74	46	46
KITLG	-0.01	0.098	-10000	0	-0.72	1	1
cell motility	-0.62	0.3	-10000	0	-0.74	46	46
PTPN6	0.034	0.009	-10000	0	-10000	0	0
EPOR	-0.25	0.15	-10000	0	-10000	0	0
STAT5A (dimer)	-0.51	0.25	-10000	0	-0.61	46	46
SOCS1	0.016	0	-10000	0	-10000	0	0
cell migration	0.36	0.18	0.44	45	-10000	0	45
SOS1	0.016	0	-10000	0	-10000	0	0
EPO	0.003	0.007	-10000	0	-10000	0	0
VAV1	0.002	0.095	-10000	0	-0.69	1	1
GRB10	-0.38	0.19	-10000	0	-0.45	46	46
PTPN11	0.029	0.007	-10000	0	-10000	0	0
SCF/KIT	-0.39	0.19	-10000	0	-0.47	45	45
GO:0007205	0.018	0.009	-10000	0	-10000	0	0
MAP2K1	-0.16	0.1	-10000	0	-0.31	2	2
CBL	0.016	0	-10000	0	-10000	0	0
KIT	-1.1	0.5	-10000	0	-1.3	45	45
MAP2K2	-0.16	0.1	-10000	0	-0.31	2	2
SHC/Grb2/SOS1	-0.33	0.17	-10000	0	-0.4	45	45
STAT5A	-0.52	0.26	-10000	0	-0.63	46	46
GRB2	0.016	0	-10000	0	-10000	0	0
response to radiation	-0.44	0.23	-10000	0	-0.5	48	48
SHC/GRAP2	0.023	0	-10000	0	-10000	0	0
PTPRO	-0.36	0.18	-10000	0	-0.44	45	45
SH2B2	-0.37	0.18	-10000	0	-0.45	45	45
DOK1	0.016	0	-10000	0	-10000	0	0
MATK	-0.37	0.19	-10000	0	-0.45	45	45
CREBBP	0.007	0.016	-10000	0	-10000	0	0
BCL2	-0.55	0.58	-10000	0	-1.4	16	16

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

Figure S2. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S2. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.021	0.008	-10000	0	-10000	0	0
NFATC2	-0.1	0.15	-10000	0	-0.48	6	6
NFATC3	-0.24	0.089	-10000	0	-0.31	25	25
CD40LG	-0.78	0.35	-10000	0	-0.94	40	40
ITCH	-0.2	0.11	-10000	0	-10000	0	0
CBLB	-0.2	0.11	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.35	0.15	-10000	0	-0.64	4	4
JUNB	0.016	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.26	0.12	-10000	0	-0.31	45	45
T cell anergy	-0.35	0.18	-10000	0	-0.43	45	45
TLE4	-0.031	0.1	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.8	0.37	-10000	0	-0.97	38	38
AP-1/NFAT1-c-4	-0.92	0.43	-10000	0	-1.1	40	40
IKZF1	-0.031	0.1	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.75	0.25	-10000	0	-0.83	48	48
AP-1/NFAT1	-0.26	0.25	-10000	0	-0.5	27	27
CALM1	-0.13	0.073	-10000	0	-10000	0	0
EGR2	-1.2	0.61	-10000	0	-1.5	41	41
EGR3	-1.2	0.6	-10000	0	-1.6	40	40
NFAT1/FOXP3	-0.053	0.1	-10000	0	-10000	0	0
EGR1	-0.35	0.35	-10000	0	-0.69	28	28
JUN	0.005	0.094	-10000	0	-0.68	1	1
EGR4	0	0.003	-10000	0	-10000	0	0
mol:Ca2+	-0.16	0.077	-10000	0	-0.19	45	45
GBP3	-0.075	0.24	-10000	0	-0.89	4	4
FOSL1	0.013	0.022	-10000	0	-10000	0	0
NFAT1-c-4/MAF/IRF4	-0.93	0.43	-10000	0	-1.2	38	38
DGKA	-0.031	0.1	-10000	0	-10000	0	0
CREM	0.015	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-1.1	0.41	-10000	0	-1.2	47	47
CTLA4	-0.036	0.083	-10000	0	-10000	0	0
NFAT1-c-4 (dimer)/EGR1	-1	0.45	-10000	0	-1.1	48	48
NFAT1-c-4 (dimer)/EGR4	-0.84	0.38	-10000	0	-0.93	48	48
FOS	-0.32	0.35	-10000	0	-0.68	26	26
IFNG	-0.26	0.24	-10000	0	-0.77	8	8
T cell activation	-0.4	0.24	-10000	0	-0.64	20	20
MAF	-0.28	0.35	-10000	0	-0.69	23	23
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.69	0.36	0.94	29	-10000	0	29
TNF	-0.86	0.36	-10000	0	-1	42	42
FASLG	-1.2	0.56	-10000	0	-1.4	50	50
TBX21	-0.084	0.25	-10000	0	-0.69	8	8
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	-0.032	0.074	-10000	0	-10000	0	0
PTPN1	-0.031	0.1	-10000	0	-10000	0	0
NFAT1-c-4/ICER1	-0.84	0.37	-10000	0	-0.93	47	47
GATA3	-0.64	0.19	-10000	0	-0.69	50	50
T-helper 1 cell differentiation	-0.25	0.24	-10000	0	-0.76	8	8
IL2RA	-0.37	0.16	-10000	0	-0.57	7	7
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.031	0.1	-10000	0	-10000	0	0
E2F1	0.006	0.051	-10000	0	-10000	0	0
PPARG	-0.49	0.32	-10000	0	-0.69	39	39
SLC3A2	-0.031	0.1	-10000	0	-10000	0	0
IRF4	0.016	0	-10000	0	-10000	0	0
PTGS2	-0.79	0.36	-10000	0	-0.96	40	40
CSF2	-0.78	0.35	-10000	0	-0.94	40	40
JunB/Fra1/NFAT1-c-4	-0.79	0.37	-10000	0	-0.97	37	37
IL4	-0.79	0.27	-10000	0	-0.87	48	48
IL5	-0.78	0.35	-10000	0	-0.94	40	40
IL2	-0.4	0.24	-10000	0	-0.65	20	20
IL3	-0.098	0.032	-10000	0	-10000	0	0
RNF128	-0.61	0.3	-10000	0	-0.74	45	45
NFATC1	-0.7	0.36	-10000	0	-0.94	29	29
CDK4	0.39	0.16	0.51	26	-10000	0	26
PTPRK	-0.052	0.19	-10000	0	-0.91	2	2
IL8	-0.8	0.35	-10000	0	-0.96	40	40
POU2F1	0.024	0	-10000	0	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

Figure S3. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S3. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	-0.076	0.24	-9999	-0.69	7	7
LAT2	-0.37	0.16	-9999	-0.49	31	31
AP1	-0.45	0.2	-9999	-0.55	39	39
mol:PIP3	-0.45	0.19	-9999	-0.6	30	30
IKBKB	-0.23	0.094	-9999	-0.3	30	30
AKT1	-0.4	0.2	-9999	-0.57	29	29
IKBKG	-0.23	0.094	-9999	-0.3	30	30
MS4A2	-0.59	0.25	-9999	-0.7	46	46
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0	0.096	-9999	-0.7	1	1
MAP3K1	-0.29	0.15	-9999	-0.41	29	29
mol:Ca2+	-0.33	0.13	-9999	-0.43	30	30
LYN	0.001	0.023	-9999	-10000	0	0
CBLB	-0.37	0.16	-9999	-0.49	31	31
SHC1	0.016	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.16	0.21	-9999	-0.4	24	24
positive regulation of cell migration	-0.29	0.26	-9999	-0.52	31	31
INPP5D	0	0	-9999	-10000	0	0
PLD2	-0.49	0.22	-9999	-0.61	37	37
PTPN13	-0.43	0.21	-9999	-0.57	32	32
PTPN11	0	0.01	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.28	0.12	-9999	-0.38	29	29
SYK	-0.008	0.043	-9999	-10000	0	0
GRB2	0.014	0	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.46	0.19	-9999	-0.62	30	30
LAT	-0.37	0.16	-9999	-0.48	32	32
PAK2	-0.33	0.16	-9999	-0.45	29	29
NFATC2	-0.16	0.054	-9999	-10000	0	0
HRAS	-0.36	0.17	-9999	-0.5	29	29
GAB2	0.016	0	-9999	-10000	0	0
PLA2G1B	0.075	0.021	-9999	-10000	0	0
Fc epsilon R1	-0.62	0.25	-9999	-0.65	51	51
Antigen/IgE/Fc epsilon R1	-0.57	0.23	-9999	-0.6	51	51
mol:GDP	-0.37	0.18	-9999	-0.51	29	29
JUN	0.002	0.095	-9999	-0.69	1	1
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0	0.096	-9999	-0.7	1	1
FOS	-0.32	0.35	-9999	-0.69	26	26
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.4	0.17	-9999	-0.44	46	46
CHUK	-0.23	0.094	-9999	-0.3	30	30
KLRG1	-0.35	0.15	-9999	-0.48	29	29
VAV1	-0.38	0.17	-9999	-0.52	29	29
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.37	0.16	-9999	-0.42	46	46
negative regulation of mast cell degranulation	-0.33	0.14	-9999	-0.45	29	29
BTK	-0.38	0.18	-9999	-0.5	31	31
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.65	0.38	-9999	-0.86	36	36
GAB2/PI3K/SHP2	-0.45	0.22	-9999	-0.63	29	29
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.42	0.22	-9999	-0.59	31	31
RAF1	0.07	0.025	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.64	0.32	-9999	-0.68	51	51
FCER1G	0.028	0.009	-9999	-10000	0	0
FCER1A	-0.44	0.34	-9999	-0.71	34	34
Antigen/IgE/Fc epsilon R1/Fyn	-0.53	0.22	-9999	-0.56	51	51
MAPK3	0.074	0.021	-9999	-10000	0	0
MAPK1	0.074	0.021	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	-0.078	0.041	-9999	-10000	0	0
DUSP1	-0.3	0.35	-9999	-0.69	24	24
NF-kappa-B/RelA	-0.14	0.048	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.37	0.16	-9999	-0.49	29	29
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.34	0.18	-9999	-0.48	29	29
FER	-0.37	0.16	-9999	-0.48	32	32
RELA	0.016	0	-9999	-10000	0	0
ITK	-0.083	0.029	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
PLCG1	-0.38	0.18	-9999	-0.53	29	29
cytokine secretion	-0.098	0.034	-9999	-10000	0	0
SPHK1	-0.38	0.17	-9999	-0.5	31	31
PTK2	-0.38	0.16	-9999	-0.52	29	29
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.49	0.2	-9999	-0.65	30	30
EDG1	-0.3	0.26	-9999	-0.52	31	31
mol:DAG	-0.46	0.21	-9999	-0.62	30	30
MAP2K2	0.071	0.022	-9999	-10000	0	0
MAP2K1	0.071	0.022	-9999	-10000	0	0
MAP2K7	0.016	0	-9999	-10000	0	0
KLRG1/SHP2	-0.32	0.14	-9999	-0.44	29	29
MAP2K4	0.004	0.008	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.68	0.33	-9999	-0.72	51	51
mol:Choline	-0.48	0.21	-9999	-0.59	37	37
SHC/Grb2/SOS1	-0.34	0.14	-9999	-0.46	29	29
FYN	0.016	0	-9999	-10000	0	0
DOK1	0.016	0	-9999	-10000	0	0
PXN	-0.35	0.15	-9999	-0.47	29	29
HCLS1	-0.37	0.16	-9999	-0.48	32	32
PRKCB	-0.33	0.14	-9999	-0.43	30	30
FCGR2B	-0.21	0.33	-9999	-0.69	17	17
IGHE	-0.013	0.005	-9999	-10000	0	0
KLRG1/SHIP	-0.33	0.15	-9999	-0.46	29	29
LCP2	-0.012	0.13	-9999	-0.69	2	2
PLA2G4A	-0.4	0.19	-9999	-0.52	32	32
RASA1	0.016	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.48	0.21	-9999	-0.59	37	37
IKK complex	-0.16	0.071	-9999	-0.21	30	30
WIPF1	0.016	0	-9999	-10000	0	0

×

Arf6 signaling events

Figure S4. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S4. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.011	0	-9999	-10000	0	0
ARNO/beta Arrestin1-2	-0.32	0.18	-9999	-0.38	45	45
EGFR	-0.066	0.22	-9999	-0.69	6	6
EPHA2	0.013	0.022	-9999	-10000	0	0
USP6	0.016	0	-9999	-10000	0	0
IQSEC1	0.002	0.095	-9999	-0.69	1	1
EGFR/EGFR/EGF/EGF	-0.17	0.3	-9999	-0.59	17	17
ARRB2	0.019	0.001	-9999	-10000	0	0
mol:GTP	0.008	0.004	-9999	-10000	0	0
ARRB1	-0.1	0.26	-9999	-0.69	9	9
FBXO8	-0.024	0.16	-9999	-0.69	3	3
TSHR	0.012	0.022	-9999	-10000	0	0
EGF	-0.17	0.31	-9999	-0.69	14	14
somatostatin receptor activity	-0.001	0	-9999	-0.001	45	45
ARAP2	0	0	-9999	0	45	45
mol:GDP	-0.25	0.07	-9999	-0.28	45	45
mol:PI-3-4-5-P3	-0.001	0	-9999	-0.001	45	45
ITGA2B	0.012	0.022	-9999	-10000	0	0
ARF6	0.015	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.031	0.059	-9999	-0.39	1	1
ADAP1	0	0	-9999	0	45	45
KIF13B	0.016	0	-9999	-10000	0	0
HGF/MET	0.019	0.02	-9999	-10000	0	0
PXN	0.016	0	-9999	-10000	0	0
ARF6/GTP	-0.24	0.073	-9999	-0.26	45	45
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.15	0.26	-9999	-0.5	18	18
ADRB2	-0.56	0.27	-9999	-0.69	44	44
receptor agonist activity	0	0	-9999	0	45	45
actin filament binding	0	0	-9999	-0.001	45	45
SRC	0.015	0	-9999	-10000	0	0
ITGB3	0.006	0.037	-9999	-10000	0	0
GNAQ	-0.001	0	-9999	-0.001	45	45
EFA6/PI-4-5-P2	-0.001	0	-9999	-0.001	45	45
ARF6/GDP	-0.076	0.055	-9999	-0.26	3	3
ARF6/GDP/GULP/ACAP1	-0.23	0.1	-9999	-0.32	20	20
alphaIIb/beta3 Integrin/paxillin/GIT1	0.034	0.025	-9999	-10000	0	0
ACAP1	0	0	-9999	0	4	4
ACAP2	0	0	-9999	0	45	45
LHCGR/beta Arrestin2	0.018	0.002	-9999	-10000	0	0
EFNA1	0.016	0	-9999	-10000	0	0
HGF	0.012	0.022	-9999	-10000	0	0
CYTH3	-0.001	0	-9999	-0.001	45	45
CYTH2	-0.004	0.001	-9999	-0.004	45	45
NCK1	0.002	0.095	-9999	-0.69	1	1
fibronectin binding	0	0	-9999	0	43	43
endosomal lumen acidification	0	0	-9999	0	19	19
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.024	0.16	-9999	-0.69	3	3
GNAQ/ARNO	-0.006	0.001	-9999	-0.006	45	45
mol:Phosphatidic acid	0	0	-9999	0	45	45
PIP3-E	0.012	0.022	-9999	-10000	0	0
MET	0.012	0.022	-9999	-10000	0	0
GNA14	0.002	0.095	-9999	-0.69	1	1
GNA15	0.015	0	-9999	-10000	0	0
GIT1	0.015	0	-9999	-10000	0	0
mol:PI-4-5-P2	-0.001	0	-9999	-0.001	45	45
GNA11	0.015	0	-9999	-10000	0	0
LHCGR	0.015	0.002	-9999	-10000	0	0
AGTR1	-0.68	0.095	-9999	-0.69	53	53
desensitization of G-protein coupled receptor protein signaling pathway	0.018	0.002	-9999	-10000	0	0
IPCEF1/ARNO	-0.12	0.21	-9999	-0.41	17	17
alphaIIb/beta3 Integrin	0.015	0.033	-9999	-10000	0	0

×

FOXM1 transcription factor network

Figure S5. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S5. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.51	0.33	-9999	-0.9	17	17
PLK1	-0.014	0.022	-9999	-10000	0	0
BIRC5	-0.088	0.072	-9999	-10000	0	0
HSPA1B	-0.52	0.33	-9999	-0.87	20	20
MAP2K1	-0.012	0.016	-9999	-10000	0	0
BRCA2	-0.52	0.33	-9999	-0.91	17	17
FOXM1	-0.6	0.4	-9999	-1.1	19	19
XRCC1	-0.51	0.33	-9999	-0.89	18	18
FOXM1B/p19	-0.58	0.34	-9999	-0.93	22	22
Cyclin D1/CDK4	-0.48	0.3	-9999	-0.84	17	17
CDC2	-0.55	0.35	-9999	-0.95	18	18
TGFA	-0.47	0.31	-9999	-0.83	17	17
SKP2	-0.51	0.33	-9999	-0.9	17	17
CCNE1	-0.075	0.084	-9999	-10000	0	0
CKS1B	-0.51	0.33	-9999	-0.89	18	18
RB1	-0.22	0.11	-9999	-0.39	2	2
FOXM1C/SP1	-0.55	0.37	-9999	-0.96	19	19
AURKB	-0.041	0.062	-9999	-10000	0	0
CENPF	-0.55	0.33	-9999	-0.92	19	19
CDK4	0.003	0.006	-9999	-10000	0	0
MYC	-0.46	0.29	-9999	-0.78	18	18
CHEK2	-0.012	0.016	-9999	-10000	0	0
ONECUT1	-0.51	0.33	-9999	-0.89	18	18
CDKN2A	-0.051	0.08	-9999	-10000	0	0
LAMA4	-0.51	0.33	-9999	-0.9	17	17
FOXM1B/HNF6	-0.57	0.38	-9999	-1	18	18
FOS	-0.8	0.53	-9999	-1.3	29	29
SP1	0.016	0	-9999	-10000	0	0
CDC25B	-0.52	0.33	-9999	-0.9	18	18
response to radiation	-0.027	0.015	-9999	-10000	0	0
CENPB	-0.51	0.33	-9999	-0.89	18	18
CENPA	-0.54	0.34	-9999	-0.94	17	17
NEK2	-0.55	0.33	-9999	-0.94	17	17
HIST1H2BA	-0.52	0.33	-9999	-0.89	18	18
CCNA2	-0.054	0.082	-9999	-10000	0	0
EP300	0.016	0	-9999	-10000	0	0
CCNB1/CDK1	-0.58	0.38	-9999	-1	17	17
CCNB2	-0.54	0.34	-9999	-0.92	19	19
CCNB1	-0.55	0.35	-9999	-0.95	18	18
ETV5	-0.51	0.33	-9999	-0.89	18	18
ESR1	-0.57	0.41	-9999	-1	19	19
CCND1	-0.49	0.31	-9999	-0.86	17	17
GSK3A	-0.003	0.012	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.073	0.083	-9999	-0.25	2	2
CDK2	-0.001	0.038	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.034	0.018	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.54	0.34	-9999	-0.89	22	22
GAS1	-1	0.46	-9999	-1.2	43	43
MMP2	-0.51	0.33	-9999	-0.89	18	18
RB1/FOXM1C	-0.5	0.33	-9999	-0.89	18	18
CREBBP	0.016	0	-9999	-10000	0	0

×

IGF1 pathway

Figure S6. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S6. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.016	0	-10000	0	-10000	0	0
PTK2	0.016	0	-10000	0	-10000	0	0
CRKL	-0.15	0.23	-10000	0	-0.4	23	23
GRB2/SOS1/SHC	0.032	0	-10000	0	-10000	0	0
HRAS	0.016	0	-10000	0	-10000	0	0
IRS1/Crk	-0.15	0.23	-10000	0	-0.4	23	23
IGF-1R heterotetramer/IGF1/PTP1B	-0.15	0.22	-10000	0	-0.43	21	21
AKT1	-0.12	0.21	-10000	0	-0.59	5	5
BAD	-0.11	0.2	-10000	0	-0.5	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.15	0.23	-10000	0	-0.4	23	23
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.15	0.23	-10000	0	-0.4	23	23
RAF1	-0.096	0.19	-10000	0	-0.5	5	5
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.14	0.22	-10000	0	-0.38	23	23
YWHAZ	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.17	0.25	-10000	0	-0.44	23	23
PIK3CA	0.002	0.095	-10000	0	-0.69	1	1
RPS6KB1	-0.12	0.21	-10000	0	-0.59	5	5
GNB2L1	0.016	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.085	0.16	-10000	0	-0.43	5	5
PXN	0.016	0	-10000	0	-10000	0	0
PIK3R1	0.002	0.095	-10000	0	-0.69	1	1
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.023	0	-10000	0	-10000	0	0
HRAS/GTP	-0.14	0.18	-10000	0	-0.34	21	21
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.1	0.18	-10000	0	-0.33	21	21
IGF-1R heterotetramer	-0.024	0.048	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.15	0.23	-10000	0	-0.4	23	23
Crk/p130 Cas/Paxillin	-0.12	0.21	-10000	0	-0.36	21	21
IGF1R	-0.024	0.048	-10000	0	-10000	0	0
IGF1	-0.27	0.36	-10000	0	-0.71	21	21
IRS2/Crk	-0.38	0.27	-10000	0	-0.48	43	43
PI3K	-0.15	0.23	-10000	0	-0.4	22	22
apoptosis	0.086	0.18	0.46	5	-10000	0	5
HRAS/GDP	0.012	0	-10000	0	-10000	0	0
PRKCD	-0.15	0.24	-10000	0	-0.45	21	21
RAF1/14-3-3 E	-0.075	0.17	-10000	0	-0.42	5	5
BAD/14-3-3	-0.092	0.19	-10000	0	-0.49	5	5
PRKCZ	-0.13	0.21	-10000	0	-0.36	22	22
Crk/p130 Cas/Paxillin/FAK1	-0.12	0.16	-10000	0	-0.49	5	5
PTPN1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.17	0.26	-10000	0	-0.48	21	21
BCAR1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.14	0.23	-10000	0	-0.4	22	22
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.016	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.15	0.23	-10000	0	-0.4	23	23
GRB10	-0.024	0.16	-10000	0	-0.69	3	3
PTPN11	-0.15	0.23	-10000	0	-0.4	23	23
IRS1	-0.17	0.24	-10000	0	-0.44	23	23
IRS2	-0.41	0.28	-10000	0	-0.51	44	44
IGF-1R heterotetramer/IGF1	-0.2	0.28	-10000	0	-0.55	21	21
GRB2	0.016	0	-10000	0	-10000	0	0
PDPK1	-0.14	0.22	-10000	0	-0.37	22	22
YWHAE	0.016	0	-10000	0	-10000	0	0
PRKD1	-0.15	0.24	-10000	0	-0.45	21	21
SHC1	0.016	0	-10000	0	-10000	0	0

×

Thromboxane A2 receptor signaling

Figure S7. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S7. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.011	0.022	-10000	0	-10000	0	0
GNB1/GNG2	-0.1	0.084	-10000	0	-0.18	29	29
AKT1	-0.075	0.13	-10000	0	-0.19	29	29
EGF	-0.17	0.31	-10000	0	-0.69	14	14
mol:TXA2	-0.001	0.001	-10000	0	-10000	0	0
FGR	-0.02	0.11	-10000	0	-10000	0	0
mol:Ca2+	-0.13	0.18	-10000	0	-0.29	29	29
LYN	-0.021	0.11	-10000	0	-10000	0	0
RhoA/GTP	-0.062	0.063	-10000	0	-0.13	9	9
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.15	0.21	-10000	0	-0.33	29	29
GNG2	0.015	0	-10000	0	-10000	0	0
ARRB2	0.016	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.018	0.037	-10000	0	-10000	0	0
G beta5/gamma2	-0.14	0.11	-10000	0	-0.24	29	29
PRKCH	-0.16	0.22	-10000	0	-0.36	30	30
DNM1	0.002	0.095	-10000	0	-0.69	1	1
TXA2/TP beta/beta Arrestin3	-0.017	0.044	-10000	0	-0.31	1	1
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
PTGDR	-0.18	0.32	-10000	0	-0.69	15	15
G12 family/GTP	-0.16	0.15	-10000	0	-0.29	29	29
ADRBK1	0.015	0	-10000	0	-10000	0	0
ADRBK2	0.015	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.014	0.01	-10000	0	-10000	0	0
mol:GDP	0.087	0.13	0.3	8	-10000	0	8
mol:NADP	0.015	0	-10000	0	-10000	0	0
RAB11A	0.016	0	-10000	0	-10000	0	0
PRKG1	0.015	0	-10000	0	-10000	0	0
mol:IP3	-0.16	0.22	-10000	0	-0.36	29	29
cell morphogenesis	0.01	0.011	-10000	0	-10000	0	0
PLCB2	-0.23	0.29	-10000	0	-0.49	29	29
mol:cGMP	-0.001	0.001	-10000	0	-10000	0	0
BLK	-0.021	0.11	-10000	0	-10000	0	0
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.026	0.11	-10000	0	-0.3	1	1
RHOA	0.016	0	-10000	0	-10000	0	0
PTGIR	0.015	0	-10000	0	-10000	0	0
PRKCB1	-0.17	0.23	-10000	0	-0.37	30	30
GNAQ	0	0	-10000	0	-10000	0	0
mol:L-citrulline	0.015	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	-0.24	0.3	-10000	0	-0.52	29	29
LCK	-0.021	0.11	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.068	0.11	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.012	0.042	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.068	0.11	-10000	0	-10000	0	0
MAPK14	-0.088	0.14	-10000	0	-0.22	29	29
TGM2/GTP	-0.18	0.24	-10000	0	-0.4	29	29
MAPK11	-0.088	0.14	-10000	0	-0.22	29	29
ARHGEF1	-0.066	0.11	-10000	0	-0.17	29	29
GNAI2	0.016	0	-10000	0	-10000	0	0
JNK cascade	-0.17	0.23	-10000	0	-0.38	29	29
RAB11/GDP	0.016	0.002	-10000	0	-10000	0	0
ICAM1	-0.12	0.17	-10000	0	-0.27	29	29
cAMP biosynthetic process	-0.15	0.2	-10000	0	-0.33	29	29
Gq family/GTP/EBP50	0.023	0.032	-10000	0	-0.21	1	1
actin cytoskeleton reorganization	0.01	0.011	-10000	0	-10000	0	0
SRC	-0.02	0.11	-10000	0	-10000	0	0
GNB5	0.006	0.037	-10000	0	-10000	0	0
GNB1	0.016	0	-10000	0	-10000	0	0
EGF/EGFR	-0.034	0.1	-10000	0	-0.32	1	1
VCAM1	-0.16	0.22	-10000	0	-0.35	29	29
TP beta/Gq family/GDP/G beta5/gamma2	0.018	0.037	-10000	0	-10000	0	0
platelet activation	-0.12	0.19	-10000	0	-0.29	29	29
PGI2/IP	0.011	0.001	-10000	0	-10000	0	0
PRKACA	-0.072	0.15	-10000	0	-0.32	15	15
Gq family/GDP/G beta5/gamma2	0.01	0.046	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2	-0.019	0.082	-10000	0	-0.61	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.059	0.14	-10000	0	-0.29	15	15
mol:DAG	-0.19	0.25	-10000	0	-0.41	29	29
EGFR	-0.066	0.22	-10000	0	-0.69	6	6
TXA2/TP alpha	-0.21	0.27	-10000	0	-0.45	29	29
Gq family/GTP	0.003	0.039	-10000	0	-0.26	1	1
YES1	-0.02	0.11	-10000	0	-10000	0	0
GNAI2/GTP	-0.062	0.1	-10000	0	-10000	0	0
PGD2/DP	-0.14	0.24	-10000	0	-0.52	15	15
SLC9A3R1	0.016	0	-10000	0	-10000	0	0
FYN	-0.02	0.11	-10000	0	-10000	0	0
mol:NO	0.015	0	-10000	0	-10000	0	0
GNA15	0.016	0	-10000	0	-10000	0	0
PGK/cGMP	0.02	0.001	-10000	0	-10000	0	0
RhoA/GDP	0.016	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.029	0.13	-10000	0	-10000	0	0
NOS3	0.015	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	-0.15	0.21	-10000	0	-0.34	29	29
PRKCB	-0.16	0.21	-10000	0	-0.35	29	29
PRKCE	-0.15	0.21	-10000	0	-0.34	29	29
PRKCD	-0.17	0.23	-10000	0	-0.37	29	29
PRKCG	-0.17	0.23	-10000	0	-0.37	29	29
muscle contraction	-0.22	0.28	-10000	0	-0.47	29	29
PRKCZ	-0.15	0.2	-10000	0	-0.34	29	29
ARR3	0.016	0	-10000	0	-10000	0	0
TXA2/TP beta	-0.054	0.12	-10000	0	-10000	0	0
PRKCQ	-0.16	0.21	-10000	0	-0.35	29	29
MAPKKK cascade	-0.2	0.26	-10000	0	-0.43	29	29
SELE	-0.18	0.23	-10000	0	-0.38	29	29
TP beta/GNAI2/GDP/G beta/gamma	-0.028	0.13	-10000	0	-10000	0	0
ROCK1	0.016	0	-10000	0	-10000	0	0
GNA14	0.002	0.095	-10000	0	-0.69	1	1
chemotaxis	-0.28	0.35	-10000	0	-0.6	29	29
GNA12	0.016	0	-10000	0	-10000	0	0
GNA13	0.016	0	-10000	0	-10000	0	0
GNA11	0.016	0	-10000	0	-10000	0	0
Rac1/GTP	0.006	0.006	-10000	0	-10000	0	0

×

Endothelins

Figure S8. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S8. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.001	0.16	-9999	-0.39	7	7
PTK2B	0.015	0	-9999	-10000	0	0
mol:Ca2+	-0.009	0.17	-9999	-0.74	2	2
EDN1	-0.058	0.24	-9999	-0.66	7	7
EDN3	-0.4	0.34	-9999	-0.69	31	31
EDN2	-0.03	0.073	-9999	-10000	0	0
HRAS/GDP	-0.16	0.15	-9999	-0.39	8	8
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.008	0.09	-9999	-0.26	1	1
ADCY4	-0.018	0.19	-9999	-0.44	8	8
ADCY5	0.003	0.13	-9999	-0.32	7	7
ADCY6	0.003	0.13	-9999	-0.32	7	7
ADCY7	0.003	0.13	-9999	-0.32	7	7
ADCY1	0.003	0.13	-9999	-0.32	7	7
ADCY2	0.003	0.13	-9999	-0.32	7	7
ADCY3	0.003	0.13	-9999	-0.32	7	7
ADCY8	0.003	0.13	-9999	-0.32	7	7
ADCY9	0.003	0.13	-9999	-0.32	7	7
arachidonic acid secretion	-0.21	0.22	-9999	-0.4	27	27
ETB receptor/Endothelin-1/Gq/GTP	-0.23	0.17	-9999	-0.32	39	39
GNAO1	0.016	0	-9999	-10000	0	0
HRAS	0.014	0.002	-9999	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.02	0.15	-9999	-0.36	7	7
ETA receptor/Endothelin-1/Gs/GTP	-0.02	0.14	-9999	-0.34	7	7
mol:GTP	-0.002	0.006	-9999	-10000	0	0
COL3A1	-0.019	0.21	-9999	-0.46	9	9
EDNRB	-0.46	0.33	-9999	-0.69	37	37
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	0	0.16	-9999	-0.39	7	7
CYSLTR1	0	0.16	-9999	-0.39	7	7
SLC9A1	-0.018	0.09	-9999	-0.23	7	7
mol:GDP	-0.17	0.16	-9999	-0.35	16	16
SLC9A3	-0.31	0.26	-9999	-0.49	30	30
RAF1	-0.23	0.2	-9999	-0.44	21	21
JUN	-0.005	0.18	-9999	-1.1	1	1
JAK2	-0.001	0.16	-9999	-0.39	7	7
mol:IP3	-0.14	0.12	-9999	-0.33	8	8
ETA receptor/Endothelin-1	-0.033	0.19	-9999	-0.47	7	7
PLCB1	-0.03	0.07	-9999	-10000	0	0
PLCB2	0.009	0.008	-9999	-10000	0	0
ETA receptor/Endothelin-3	-0.29	0.25	-9999	-0.51	31	31
FOS	-0.47	0.45	-9999	-0.93	26	26
Gai/GDP	-0.012	0.11	-9999	-0.72	1	1
CRK	0.015	0	-9999	-10000	0	0
mol:Ca ++	-0.17	0.18	-9999	-0.5	9	9
BCAR1	0.016	0	-9999	-10000	0	0
PRKCB1	-0.14	0.14	-9999	-0.37	9	9
GNAQ	-0.003	0.007	-9999	-10000	0	0
GNAZ	0.016	0	-9999	-10000	0	0
GNAL	0.016	0	-9999	-10000	0	0
Gs family/GDP	-0.16	0.13	-9999	-0.35	11	11
ETA receptor/Endothelin-1/Gq/GTP	-0.006	0.11	-9999	-0.3	2	2
MAPK14	-0.18	0.14	-9999	-0.31	20	20
TRPC6	-0.011	0.18	-9999	-0.79	2	2
GNAI2	0.016	0	-9999	-10000	0	0
GNAI3	0.002	0.095	-9999	-0.69	1	1
GNAI1	-0.024	0.16	-9999	-0.69	3	3
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.2	0.15	-9999	-0.32	25	25
ETB receptor/Endothelin-2	-0.36	0.26	-9999	-0.54	37	37
ETB receptor/Endothelin-3	-0.61	0.31	-9999	-0.7	47	47
ETB receptor/Endothelin-1	-0.39	0.28	-9999	-0.55	39	39
MAPK3	-0.4	0.38	-9999	-0.78	26	26
MAPK1	-0.4	0.38	-9999	-0.78	26	26
Rac1/GDP	-0.16	0.15	-9999	-0.39	8	8
cAMP biosynthetic process	0.043	0.14	-9999	-0.4	2	2
MAPK8	-0.01	0.14	-9999	-0.54	2	2
SRC	0.015	0	-9999	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.19	0.16	-9999	-0.42	10	10
p130Cas/CRK/Src/PYK2	-0.13	0.15	-9999	-0.45	5	5
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.16	0.15	-9999	-0.39	8	8
COL1A2	-0.25	0.24	-9999	-0.65	9	9
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.008	0.056	-9999	-10000	0	0
mol:DAG	-0.14	0.12	-9999	-0.33	8	8
MAP2K2	-0.31	0.28	-9999	-0.56	27	27
MAP2K1	-0.31	0.28	-9999	-0.56	27	27
EDNRA	0.031	0.042	-9999	-10000	0	0
positive regulation of muscle contraction	0.007	0.14	-9999	-0.33	7	7
Gq family/GDP	-0.12	0.14	-9999	-0.4	6	6
HRAS/GTP	-0.18	0.14	-9999	-0.32	24	24
PRKCH	-0.16	0.16	-9999	-0.39	11	11
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	-0.13	0.12	-9999	-0.32	7	7
PRKCB	-0.14	0.12	-9999	-0.31	9	9
PRKCE	-0.13	0.12	-9999	-0.32	7	7
PRKCD	-0.13	0.12	-9999	-0.32	7	7
PRKCG	-0.13	0.12	-9999	-0.32	7	7
regulation of vascular smooth muscle contraction	-0.54	0.52	-9999	-1.1	26	26
PRKCQ	-0.15	0.11	-9999	-0.32	10	10
PLA2G4A	-0.23	0.24	-9999	-0.43	27	27
GNA14	-0.003	0.096	-9999	-0.7	1	1
GNA15	0.014	0.005	-9999	-10000	0	0
GNA12	0.016	0	-9999	-10000	0	0
GNA11	0.014	0.005	-9999	-10000	0	0
Rac1/GTP	-0.02	0.15	-9999	-0.36	7	7
MMP1	-0.007	0.1	-9999	-10000	0	0

×

Glucocorticoid receptor regulatory network

Figure S9. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S9. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	-0.013	0.052	-10000	0	-10000	0	0
SMARCC2	0.016	0	-10000	0	-10000	0	0
SMARCC1	0.013	0.022	-10000	0	-10000	0	0
TBX21	-0.12	0.34	-10000	0	-0.9	8	8
SUMO2	0.008	0.008	-10000	0	-10000	0	0
STAT1 (dimer)	0.016	0.037	-10000	0	-10000	0	0
FKBP4	0.016	0	-10000	0	-10000	0	0
FKBP5	-0.037	0.18	-10000	0	-0.69	4	4
GR alpha/HSP90/FKBP51/HSP90	-0.097	0.21	0.25	3	-0.45	8	11
PRL	0.022	0.082	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.038	0.22	0.43	10	-0.5	1	11
RELA	-0.1	0.11	-10000	0	-0.29	6	6
FGG	0.052	0.21	0.41	8	-0.49	1	9
GR beta/TIF2	-0.089	0.19	0.27	3	-0.37	10	13
IFNG	-0.29	0.25	-10000	0	-0.66	11	11
apoptosis	-0.18	0.19	-10000	0	-0.43	10	10
CREB1	0.024	0.011	-10000	0	-10000	0	0
histone acetylation	0.37	0.21	0.48	38	-10000	0	38
BGLAP	0.01	0.1	-10000	0	-10000	0	0
GR/PKAc	-0.049	0.15	0.26	1	-0.35	3	4
NF kappa B1 p50/RelA	-0.19	0.22	-10000	0	-0.39	23	23
SMARCD1	0.016	0	-10000	0	-10000	0	0
MDM2	0.11	0.053	0.21	5	-10000	0	5
GATA3	-0.63	0.19	-10000	0	-0.68	50	50
AKT1	0.004	0.004	-10000	0	-10000	0	0
CSF2	0.2	0.14	0.38	4	-10000	0	4
GSK3B	0.008	0.008	-10000	0	-10000	0	0
NR1I3	-0.15	0.17	-10000	0	-10000	0	0
CSN2	0.044	0.18	0.35	8	-0.45	1	9
BRG1/BAF155/BAF170/BAF60A	0.036	0.018	-10000	0	-10000	0	0
NFATC1	0	0.13	-10000	0	-0.68	2	2
POU2F1	0.024	0	-10000	0	-10000	0	0
CDKN1A	0.052	0.022	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.007	0.007	-10000	0	-10000	0	0
SFN	-0.012	0.061	-10000	0	-10000	0	0
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.088	0.2	0.26	1	-0.44	7	8
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.42	0.43	-10000	0	-0.83	28	28
JUN	-0.12	0.19	-10000	0	-0.47	5	5
IL4	-0.007	0.13	-10000	0	-0.5	1	1
CDK5R1	0.012	0.004	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.45	0.25	-10000	0	-0.56	40	40
GR alpha/HSP90/FKBP51/HSP90/PP5C	-0.079	0.19	0.26	1	-0.46	6	7
cortisol/GR alpha (monomer)	0.058	0.26	0.45	13	-0.49	2	15
NCOA2	0.016	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.43	0.35	-10000	0	-0.78	26	26
AP-1/NFAT1-c-4	-0.6	0.36	-10000	0	-0.82	35	35
AFP	-0.065	0.15	-10000	0	-0.54	1	1
SUV420H1	0.016	0	-10000	0	-10000	0	0
IRF1	0.041	0.14	-10000	0	-10000	0	0
TP53	0.038	0.012	-10000	0	-10000	0	0
PPP5C	0.016	0	-10000	0	-10000	0	0
KRT17	-0.95	0.62	-10000	0	-1.3	38	38
KRT14	-1.2	0.31	-10000	0	-1.2	51	51
TBP	0.026	0.001	-10000	0	-10000	0	0
CREBBP	0.31	0.083	0.32	51	-10000	0	51
HDAC1	0.011	0.002	-10000	0	-10000	0	0
HDAC2	0.012	0	-10000	0	-10000	0	0
AP-1	-0.6	0.37	-10000	0	-0.83	35	35
MAPK14	0.008	0.008	-10000	0	-10000	0	0
MAPK10	0.005	0.024	-10000	0	-10000	0	0
MAPK11	0.008	0.008	-10000	0	-10000	0	0
KRT5	-0.84	0.65	-10000	0	-1.3	33	33
interleukin-1 receptor activity	-0.003	0.001	-10000	0	-10000	0	0
NCOA1	0.018	0.001	-10000	0	-10000	0	0
STAT1	0.016	0.037	-10000	0	-10000	0	0
CGA	0.006	0.11	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.069	0.16	0.34	10	-10000	0	10
MAPK3	0.008	0.008	-10000	0	-10000	0	0
MAPK1	0.008	0.008	-10000	0	-10000	0	0
ICAM1	-0.13	0.18	-10000	0	-0.53	3	3
NFKB1	-0.1	0.11	-10000	0	-0.29	6	6
MAPK8	-0.028	0.14	-10000	0	-0.33	5	5
MAPK9	-0.005	0.094	-10000	0	-0.69	1	1
cortisol/GR alpha (dimer)	-0.19	0.18	-10000	0	-0.44	10	10
BAX	0.048	0.034	-10000	0	-10000	0	0
POMC	0.015	0.14	-10000	0	-10000	0	0
EP300	0.31	0.084	0.33	48	-10000	0	48
cortisol/GR alpha (dimer)/p53	0.061	0.23	0.42	13	-0.49	1	14
proteasomal ubiquitin-dependent protein catabolic process	0.07	0.051	0.17	2	-10000	0	2
SGK1	0.33	0.085	0.35	51	-10000	0	51
IL13	-0.67	0.27	-10000	0	-0.78	43	43
IL6	-0.4	0.51	-10000	0	-1.1	18	18
PRKACG	0.016	0	-10000	0	-10000	0	0
IL5	-0.52	0.21	-10000	0	-0.63	38	38
IL2	-0.28	0.24	-10000	0	-0.63	11	11
CDK5	0.012	0.004	-10000	0	-10000	0	0
PRKACB	0.016	0	-10000	0	-10000	0	0
HSP90AA1	0.016	0	-10000	0	-10000	0	0
IL8	-0.15	0.18	-10000	0	-0.56	3	3
CDK5R1/CDK5	0.011	0.012	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.11	0.16	-10000	0	-0.43	6	6
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.058	0.21	0.43	9	-0.45	1	10
SMARCA4	0.01	0.031	-10000	0	-10000	0	0
chromatin remodeling	0.032	0.16	0.3	8	-0.3	1	9
NF kappa B1 p50/RelA/Cbp	0.082	0.22	0.38	11	-0.33	1	12
JUN (dimer)	-0.11	0.19	-10000	0	-0.47	5	5
YWHAH	0.016	0	-10000	0	-10000	0	0
VIPR1	0	0.15	-10000	0	-0.59	2	2
NR3C1	-0.099	0.28	0.32	7	-0.41	21	28
NR4A1	0.023	0.006	-10000	0	-10000	0	0
TIF2/SUV420H1	0.023	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.18	0.19	-10000	0	-0.43	10	10
cortisol/GR alpha (dimer)/Src-1	0.046	0.22	0.43	11	-0.49	1	12
PBX1	0.024	0	-10000	0	-10000	0	0
POU1F1	0.024	0	-10000	0	-10000	0	0
SELE	-0.47	0.55	-10000	0	-1.1	22	22
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.032	0.16	0.31	8	-0.31	1	9
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.058	0.21	0.43	9	-0.45	1	10
mol:cortisol	0.15	0.092	0.23	22	-10000	0	22
MMP1	-0.15	0.086	-10000	0	-10000	0	0

×

S1P1 pathway

Figure S10. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S10. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.22	0.2	-9999	-0.39	31	31
PDGFRB	0.015	0.003	-9999	-10000	0	0
SPHK1	-0.021	0.1	-9999	-0.76	1	1
mol:S1P	-0.019	0.091	-9999	-0.65	1	1
S1P1/S1P/Gi	-0.15	0.21	-9999	-0.56	6	6
GNAO1	0.018	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/PLCgamma1	-0.09	0.16	-9999	-0.47	5	5
PLCG1	-0.12	0.18	-9999	-0.53	5	5
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.015	0.003	-9999	-10000	0	0
GNAI2	0.018	0.003	-9999	-10000	0	0
GNAI3	0.002	0.096	-9999	-0.7	1	1
GNAI1	-0.024	0.16	-9999	-0.69	3	3
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.45	0.41	-9999	-0.8	31	31
S1P1/S1P	-0.35	0.34	-9999	-0.64	31	31
negative regulation of cAMP metabolic process	-0.14	0.2	-9999	-0.54	6	6
MAPK3	-0.13	0.21	-9999	-0.6	5	5
calcium-dependent phospholipase C activity	0	0.002	-9999	-10000	0	0
Rac1/GDP	0.012	0	-9999	-10000	0	0
RhoA/GDP	0.012	0	-9999	-10000	0	0
KDR	-0.087	0.094	-9999	-10000	0	0
PLCB2	-0.3	0.3	-9999	-0.55	31	31
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.3	0.26	-9999	-0.52	31	31
receptor internalization	-0.32	0.31	-9999	-0.58	31	31
PTGS2	-0.12	0.22	-9999	-0.91	2	2
Rac1/GTP	-0.3	0.26	-9999	-0.52	31	31
RHOA	0.016	0	-9999	-10000	0	0
VEGFA	-0.17	0.15	-9999	-0.36	16	16
negative regulation of T cell proliferation	-0.14	0.2	-9999	-0.54	6	6
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.015	0.003	-9999	-10000	0	0
MAPK1	-0.13	0.21	-9999	-0.6	5	5
S1P1/S1P/PDGFB-D/PDGFRB	-0.35	0.35	-9999	-0.65	31	31
ABCC1	-0.008	0.057	-9999	-10000	0	0

×

EGFR-dependent Endothelin signaling events

Figure S11. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S11. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.016	0	-9999	-10000	0	0
EGFR	-0.066	0.22	-9999	-0.69	6	6
EGF/EGFR	-0.18	0.24	-9999	-0.44	22	22
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.1	0.23	-9999	-0.43	17	17
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.016	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.17	0.31	-9999	-0.69	14	14
EGF/EGFR dimer/SHC	-0.14	0.26	-9999	-0.51	17	17
mol:GDP	-0.13	0.21	-9999	-0.42	17	17
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.076	0.24	-9999	-0.69	7	7
GRB2/SOS1	0.023	0	-9999	-10000	0	0
HRAS/GTP	-0.12	0.2	-9999	-0.39	17	17
SHC1	0.016	0	-9999	-10000	0	0
HRAS/GDP	-0.12	0.2	-9999	-0.39	17	17
FRAP1	-0.093	0.22	-9999	-0.4	17	17
EGF/EGFR dimer	-0.17	0.3	-9999	-0.59	17	17
SOS1	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.046	0.18	-9999	-0.51	7	7

×

HIF-1-alpha transcription factor network

Figure S12. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S12. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.27	0.3	-9999	-0.73	10	10
HDAC7	-0.003	0.005	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.22	0.23	-9999	-0.65	6	6
SMAD4	0.017	0	-9999	-10000	0	0
ID2	-0.27	0.3	-9999	-0.73	10	10
AP1	-0.25	0.27	-9999	-0.51	27	27
ABCG2	-0.3	0.36	-9999	-0.86	11	11
HIF1A	-0.04	0.054	-9999	-10000	0	0
TFF3	-0.36	0.4	-9999	-0.87	15	15
GATA2	-0.014	0.062	-9999	-10000	0	0
AKT1	-0.041	0.057	-9999	-10000	0	0
response to hypoxia	-0.063	0.061	-9999	-10000	0	0
MCL1	-0.27	0.3	-9999	-0.74	9	9
NDRG1	-0.27	0.31	-9999	-0.74	10	10
SERPINE1	-0.27	0.31	-9999	-0.73	10	10
FECH	-0.27	0.3	-9999	-0.74	9	9
FURIN	-0.27	0.3	-9999	-0.74	9	9
NCOA2	0.017	0.001	-9999	-10000	0	0
EP300	-0.038	0.075	-9999	-10000	0	0
HMOX1	-0.27	0.3	-9999	-0.73	10	10
BHLHE40	-0.28	0.3	-9999	-0.69	13	13
BHLHE41	-0.28	0.3	-9999	-0.69	13	13
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.019	0.055	-9999	-10000	0	0
ENG	-0.001	0.067	-9999	-10000	0	0
JUN	0.001	0.098	-9999	-0.71	1	1
RORA	-0.29	0.32	-9999	-0.73	12	12
ABCB1	-0.18	0.35	-9999	-1.2	6	6
TFRC	-0.28	0.31	-9999	-0.73	10	10
CXCR4	-0.27	0.3	-9999	-0.74	9	9
TF	-0.28	0.32	-9999	-0.76	12	12
CITED2	-0.28	0.32	-9999	-0.74	11	11
HIF1A/ARNT	-0.32	0.3	-9999	-0.81	10	10
LDHA	-0.028	0.04	-9999	-10000	0	0
ETS1	-0.27	0.3	-9999	-0.73	10	10
PGK1	-0.27	0.3	-9999	-0.73	10	10
NOS2	-0.28	0.3	-9999	-0.69	13	13
ITGB2	-0.27	0.31	-9999	-0.73	10	10
ALDOA	-0.27	0.3	-9999	-0.73	10	10
Cbp/p300/CITED2	-0.27	0.32	-9999	-0.79	9	9
FOS	-0.33	0.35	-9999	-0.69	26	26
HK2	-0.27	0.3	-9999	-0.73	10	10
SP1	0.017	0.029	-9999	-10000	0	0
GCK	-0.047	0.11	-9999	-10000	0	0
HK1	-0.27	0.3	-9999	-0.74	9	9
NPM1	-0.27	0.3	-9999	-0.73	10	10
EGLN1	-0.27	0.3	-9999	-0.73	10	10
CREB1	0.024	0	-9999	-10000	0	0
PGM1	-0.27	0.3	-9999	-0.73	10	10
SMAD3	0.017	0	-9999	-10000	0	0
EDN1	-0.24	0.39	-9999	-1.2	7	7
IGFBP1	-0.27	0.3	-9999	-0.73	10	10
VEGFA	-0.22	0.26	-9999	-0.62	8	8
HIF1A/JAB1	-0.012	0.031	-9999	-10000	0	0
CP	-0.31	0.32	-9999	-0.73	13	13
CXCL12	-0.63	0.34	-9999	-0.86	30	30
COPS5	0.017	0	-9999	-10000	0	0
SMAD3/SMAD4	0.026	0	-9999	-10000	0	0
BNIP3	-0.28	0.31	-9999	-0.74	10	10
EGLN3	-0.29	0.31	-9999	-0.71	13	13
CA9	-0.29	0.31	-9999	-0.76	10	10
TERT	-0.27	0.3	-9999	-0.73	10	10
ENO1	-0.27	0.3	-9999	-0.74	9	9
PFKL	-0.27	0.3	-9999	-0.73	10	10
NCOA1	0.016	0	-9999	-10000	0	0
ADM	-0.28	0.31	-9999	-0.75	10	10
ARNT	-0.041	0.054	-9999	-10000	0	0
HNF4A	0.02	0	-9999	-10000	0	0
ADFP	-0.33	0.36	-9999	-0.82	14	14
SLC2A1	-0.21	0.25	-9999	-0.65	6	6
LEP	-0.52	0.39	-9999	-0.87	23	23
HIF1A/ARNT/Cbp/p300	-0.24	0.24	-9999	-0.68	6	6
EPO	-0.13	0.19	-9999	-10000	0	0
CREBBP	-0.038	0.075	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/HDAC7	-0.25	0.24	-9999	-0.67	8	8
PFKFB3	-0.27	0.3	-9999	-0.74	9	9
NT5E	-0.28	0.32	-9999	-0.73	12	12

×

IL4-mediated signaling events

Figure S13. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S13. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.4	0.43	-10000	0	-1	13	13
STAT6 (cleaved dimer)	-0.42	0.39	-10000	0	-0.99	13	13
IGHG1	-0.14	0.17	-10000	0	-0.32	11	11
IGHG3	-0.39	0.41	-10000	0	-0.97	13	13
AKT1	-0.19	0.2	-10000	0	-0.54	3	3
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.092	0.16	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.18	0.22	-10000	0	-0.47	7	7
THY1	-0.4	0.44	-10000	0	-1	13	13
MYB	-0.23	0.34	-10000	0	-0.69	19	19
HMGA1	-0.006	0.055	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.2	0.25	-10000	0	-0.5	12	12
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.16	0.21	-10000	0	-0.46	3	3
SP1	0.025	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0	0.13	-10000	0	-0.68	2	2
STAT6 (dimer)/ETS1	-0.36	0.43	-10000	0	-0.96	13	13
SOCS1	-0.23	0.3	-10000	0	-0.65	11	11
SOCS3	-0.15	0.22	-10000	0	-10000	0	0
FCER2	-0.42	0.34	-10000	0	-0.69	23	23
PARP14	0.017	0.001	-10000	0	-10000	0	0
CCL17	-0.4	0.43	-10000	0	-1	13	13
GRB2	0.016	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.13	0.18	-10000	0	-10000	0	0
T cell proliferation	-0.48	0.41	-10000	0	-1	13	13
IL4R/JAK1	-0.4	0.44	-10000	0	-1	13	13
EGR2	-0.97	0.61	-10000	0	-1.3	43	43
JAK2	-0.006	0.031	-10000	0	-10000	0	0
JAK3	0.022	0.005	-10000	0	-10000	0	0
PIK3R1	0.002	0.095	-10000	0	-0.69	1	1
JAK1	0.008	0.015	-10000	0	-10000	0	0
COL1A2	-0.11	0.15	-10000	0	-10000	0	0
CCL26	-0.4	0.43	-10000	0	-1	13	13
IL4R	-0.43	0.48	-10000	0	-1.1	13	13
PTPN6	0.028	0.012	-10000	0	-10000	0	0
IL13RA2	-0.4	0.44	-10000	0	-1	13	13
IL13RA1	-0.006	0.031	-10000	0	-10000	0	0
IRF4	-0.038	0.1	-10000	0	-10000	0	0
ARG1	-0.076	0.13	-10000	0	-10000	0	0
CBL	-0.18	0.23	-10000	0	-0.48	11	11
GTF3A	0.018	0.011	-10000	0	-10000	0	0
PIK3CA	0.002	0.095	-10000	0	-0.69	1	1
IL13RA1/JAK2	-0.011	0.047	-10000	0	-10000	0	0
IRF4/BCL6	-0.04	0.1	-10000	0	-0.46	1	1
CD40LG	0.026	0	-10000	0	-10000	0	0
MAPK14	-0.18	0.23	-10000	0	-0.52	4	4
mitosis	-0.18	0.2	-10000	0	-0.51	3	3
STAT6	-0.45	0.5	-10000	0	-1.1	13	13
SPI1	0.023	0	-10000	0	-10000	0	0
RPS6KB1	-0.17	0.19	-10000	0	-0.52	2	2
STAT6 (dimer)	-0.45	0.5	-10000	0	-1.1	13	13
STAT6 (dimer)/PARP14	-0.42	0.45	-10000	0	-1.1	13	13
mast cell activation	0.009	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.15	0.2	-10000	0	-0.52	2	2
FRAP1	-0.19	0.2	-10000	0	-0.54	3	3
LTA	-0.4	0.43	-10000	0	-1	13	13
FES	0.016	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.44	0.48	1.1	13	-10000	0	13
CCL11	-0.38	0.42	-10000	0	-0.97	13	13
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.14	0.2	-10000	0	-0.45	1	1
IL2RG	0.022	0.005	-10000	0	-10000	0	0
IL10	-0.4	0.43	-10000	0	-1	13	13
IRS1	-0.063	0.22	-10000	0	-0.69	6	6
IRS2	-0.43	0.34	-10000	0	-0.69	34	34
IL4	-0.081	0.12	-10000	0	-10000	0	0
IL5	-0.4	0.43	-10000	0	-1	13	13
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.33	0.36	-10000	0	-0.8	12	12
COL1A1	-0.15	0.18	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.4	0.45	-10000	0	-1	13	13
IL2R gamma/JAK3	0.03	0.005	-10000	0	-10000	0	0
TFF3	-0.55	0.6	-10000	0	-1.3	16	16
ALOX15	-0.4	0.43	-10000	0	-1	13	13
MYBL1	0.016	0	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.38	0.34	-10000	0	-0.83	13	13
SHC1	0.016	0	-10000	0	-10000	0	0
CEBPB	0.023	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.28	0.2	-10000	0	-0.51	13	13
mol:PI-3-4-5-P3	-0.19	0.2	-10000	0	-0.54	3	3
PI3K	-0.2	0.21	-10000	0	-0.56	3	3
DOK2	0.002	0.095	-10000	0	-0.69	1	1
ETS1	0.026	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.12	0.17	-10000	0	-10000	0	0
ITGB3	-0.4	0.44	-10000	0	-1	13	13
PIGR	-0.5	0.61	-10000	0	-1.4	13	13
IGHE	0.004	0.059	-10000	0	-10000	0	0
MAPKKK cascade	-0.11	0.16	-10000	0	-10000	0	0
BCL6	0.001	0.095	-10000	0	-0.69	1	1
OPRM1	-0.4	0.43	-10000	0	-1	13	13
RETNLB	-0.4	0.43	-10000	0	-1	13	13
SELP	-0.91	0.7	-10000	0	-1.4	37	37
AICDA	-0.39	0.44	-10000	0	-1	13	13

×

FAS signaling pathway (CD95)

Figure S14. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S14. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.079	0.12	0.27	16	-10000	0	16
RFC1	0.079	0.12	0.27	16	-10000	0	16
PRKDC	0.078	0.12	0.27	16	-10000	0	16
RIPK1	0.018	0.005	-10000	0	-10000	0	0
CASP7	-0.023	0.034	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	0.017	0.12	0.25	6	-0.32	3	9
MAP2K4	-0.039	0.15	-10000	0	-0.35	2	2
mol:ceramide	-0.034	0.13	-10000	0	-0.44	2	2
GSN	0.028	0.16	0.27	12	-0.42	2	14
FASLG/FAS/FADD/FAF1/Caspase 8	0.011	0.12	0.23	1	-0.37	2	3
FAS	-0.054	0.2	-10000	0	-0.69	5	5
BID	0.002	0.008	-10000	0	-10000	0	0
MAP3K1	0.003	0.096	-10000	0	-0.24	1	1
MAP3K7	0.011	0.007	-10000	0	-10000	0	0
RB1	0.079	0.12	0.27	16	-10000	0	16
CFLAR	0.005	0.096	-10000	0	-0.69	1	1
HGF/MET	-0.084	0.2	-10000	0	-0.44	13	13
ARHGDIB	0.037	0.17	0.26	14	-0.43	3	17
FADD	0.011	0.008	-10000	0	-10000	0	0
actin filament polymerization	-0.028	0.16	0.42	2	-0.27	12	14
NFKB1	-0.063	0.095	-10000	0	-0.26	1	1
MAPK8	-0.083	0.22	-10000	0	-0.39	17	17
DFFA	0.079	0.12	0.27	16	-10000	0	16
DNA fragmentation during apoptosis	0.079	0.12	0.26	16	-10000	0	16
FAS/FADD/MET	-0.022	0.13	-10000	0	-0.44	5	5
CFLAR/RIP1	0.005	0.072	-10000	0	-0.52	1	1
FAIM3	0.011	0.031	-10000	0	-10000	0	0
FAF1	0.012	0.008	-10000	0	-10000	0	0
PARP1	0.076	0.12	0.27	15	-10000	0	15
DFFB	0.079	0.12	0.27	16	-10000	0	16
CHUK	-0.054	0.083	-10000	0	-10000	0	0
FASLG	0.012	0.008	-10000	0	-10000	0	0
FAS/FADD	-0.034	0.16	-10000	0	-0.52	5	5
HGF	0.013	0.022	-10000	0	-10000	0	0
LMNA	0.072	0.11	0.24	16	-10000	0	16
CASP6	0.079	0.12	0.27	16	-10000	0	16
CASP10	0.011	0.008	-10000	0	-10000	0	0
CASP3	0.095	0.14	0.32	16	-10000	0	16
PTPN13	-0.15	0.3	-10000	0	-0.69	13	13
CASP8	0.002	0.013	-10000	0	-10000	0	0
IL6	-0.34	0.57	-10000	0	-1.2	17	17
MET	0.013	0.022	-10000	0	-10000	0	0
ICAD/CAD	0.074	0.11	0.25	16	-10000	0	16
FASLG/FAS/FADD/FAF1/Caspase 10	-0.035	0.13	-10000	0	-0.44	2	2
activation of caspase activity by cytochrome c	0.002	0.008	-10000	0	-10000	0	0
PAK2	0.079	0.12	0.26	16	-10000	0	16
BCL2	-0.19	0.32	-10000	0	-0.69	16	16

×

Ephrin B reverse signaling

Figure S15. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S15. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.016	0	-10000	0	-10000	0	0
EPHB2	0.001	0.047	-10000	0	-10000	0	0
EFNB1	0.006	0.1	-10000	0	-0.51	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.002	0.14	-10000	0	-0.39	6	6
Ephrin B2/EPHB1-2	-0.015	0.12	-10000	0	-0.4	5	5
neuron projection morphogenesis	-0.039	0.12	-10000	0	-0.37	6	6
Ephrin B1/EPHB1-2/Tiam1	-0.005	0.15	-10000	0	-0.42	6	6
DNM1	0.003	0.095	-10000	0	-0.69	1	1
cell-cell signaling	0.001	0.001	-10000	0	-10000	0	0
MAP2K4	-0.12	0.26	-10000	0	-0.58	13	13
YES1	-0.19	0.34	-10000	0	-0.8	13	13
Ephrin B1/EPHB1-2/NCK2	-0.005	0.15	-10000	0	-0.42	6	6
PI3K	-0.13	0.28	-10000	0	-0.6	14	14
mol:GDP	-0.006	0.15	-10000	0	-0.41	6	6
ITGA2B	0.013	0.022	-10000	0	-10000	0	0
endothelial cell proliferation	0.021	0.001	-10000	0	-10000	0	0
FYN	-0.19	0.34	-10000	0	-0.8	13	13
MAP3K7	-0.13	0.27	-10000	0	-0.62	13	13
FGR	-0.19	0.34	-10000	0	-0.8	13	13
TIAM1	0.016	0	-10000	0	-10000	0	0
PIK3R1	0.002	0.095	-10000	0	-0.69	1	1
RGS3	0.016	0	-10000	0	-10000	0	0
cell adhesion	-0.11	0.26	-10000	0	-0.54	14	14
LYN	-0.19	0.34	-10000	0	-0.8	13	13
Ephrin B1/EPHB1-2/Src Family Kinases	-0.18	0.32	-10000	0	-0.74	13	13
Ephrin B1/EPHB1-2	-0.16	0.29	-10000	0	-0.68	13	13
SRC	-0.19	0.34	-10000	0	-0.8	13	13
ITGB3	0.006	0.037	-10000	0	-10000	0	0
EPHB1	-0.049	0.2	-10000	0	-0.69	5	5
EPHB4	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.022	0.001	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.015	0.033	-10000	0	-10000	0	0
BLK	-0.19	0.34	-10000	0	-0.8	13	13
HCK	-0.19	0.34	-10000	0	-0.8	13	13
regulation of stress fiber formation	0.006	0.15	0.41	6	-10000	0	6
MAPK8	-0.1	0.25	-10000	0	-0.55	13	13
Ephrin B1/EPHB1-2/RGS3	-0.005	0.15	-10000	0	-0.42	6	6
endothelial cell migration	-0.12	0.23	-10000	0	-0.53	13	13
NCK2	0.016	0	-10000	0	-10000	0	0
PTPN13	-0.18	0.34	-10000	0	-0.78	13	13
regulation of focal adhesion formation	0.006	0.15	0.41	6	-10000	0	6
chemotaxis	0.006	0.15	0.41	6	-10000	0	6
PIK3CA	0.002	0.095	-10000	0	-0.69	1	1
Rac1/GTP	-0.039	0.13	-10000	0	-0.38	6	6
angiogenesis	-0.16	0.29	-10000	0	-0.67	13	13
LCK	-0.19	0.34	-10000	0	-0.8	13	13

×

Nongenotropic Androgen signaling

Figure S16. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S16. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.012	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.004	0.11	-10000	0	-0.4	4	4
regulation of S phase of mitotic cell cycle	-0.005	0.12	-10000	0	-0.35	5	5
GNAO1	0.015	0	-10000	0	-10000	0	0
HRAS	0.014	0.002	-10000	0	-10000	0	0
SHBG/T-DHT	0.01	0	-10000	0	-10000	0	0
PELP1	0.011	0.022	-10000	0	-10000	0	0
AKT1	0.013	0.001	-10000	0	-10000	0	0
MAP2K1	-0.038	0.099	-10000	0	-0.3	4	4
T-DHT/AR	-0.03	0.14	-10000	0	-0.52	4	4
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.004	0.004	-10000	0	-0.008	26	26
GNAI2	0.015	0	-10000	0	-10000	0	0
GNAI3	0.002	0.095	-10000	0	-0.69	1	1
GNAI1	-0.024	0.16	-10000	0	-0.69	3	3
mol:GDP	-0.045	0.14	-10000	0	-0.48	5	5
cell proliferation	-0.15	0.2	-10000	0	-0.33	26	26
PIK3CA	0.002	0.095	-10000	0	-0.69	1	1
FOS	-0.36	0.42	-10000	0	-0.8	26	26
mol:Ca2+	-0.013	0.023	-10000	0	-0.095	3	3
MAPK3	-0.094	0.14	-10000	0	-10000	0	0
MAPK1	-0.072	0.11	-10000	0	-0.19	1	1
PIK3R1	0.002	0.095	-10000	0	-0.69	1	1
mol:IP3	-0.002	0.003	-10000	0	-0.005	26	26
cAMP biosynthetic process	0.008	0.021	-10000	0	-10000	0	0
GNG2	0.016	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	-0.002	0.003	-10000	0	-0.005	26	26
HRAS/GTP	-0.039	0.089	-10000	0	-0.35	4	4
actin cytoskeleton reorganization	-0.013	0.094	-10000	0	-0.7	1	1
SRC	0.014	0.002	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.002	0.003	-10000	0	-0.005	26	26
PI3K	0.005	0.12	-10000	0	-0.84	1	1
apoptosis	0.16	0.21	0.36	26	-10000	0	26
T-DHT/AR/PELP1	-0.02	0.12	-10000	0	-0.44	4	4
HRAS/GDP	-0.034	0.13	-10000	0	-0.45	5	5
CREB1	-0.17	0.22	-10000	0	-0.39	26	26
RAC1-CDC42/GTP	-0.013	0.096	-10000	0	-0.72	1	1
AR	-0.039	0.18	-10000	0	-0.69	4	4
GNB1	0.016	0	-10000	0	-10000	0	0
RAF1	-0.03	0.096	-10000	0	-0.32	4	4
RAC1-CDC42/GDP	-0.024	0.13	-10000	0	-0.43	5	5
T-DHT/AR/PELP1/Src	-0.012	0.11	-10000	0	-0.4	4	4
MAP2K2	-0.038	0.099	-10000	0	-0.3	4	4
T-DHT/AR/PELP1/Src/PI3K	-0.005	0.12	-10000	0	-0.35	5	5
GNAZ	0.015	0	-10000	0	-10000	0	0
SHBG	0.016	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.021	0.11	-10000	0	-0.65	1	1
mol:T-DHT	-0.001	0.002	-10000	0	-0.003	26	26
RAC1	0.016	0	-10000	0	-10000	0	0
GNRH1	-0.027	0.14	-10000	0	-0.52	4	4
Gi family/GTP	-0.008	0.11	-10000	0	-0.36	3	3
CDC42	0.016	0	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

Figure S17. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S17. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.03	0.19	-9999	-0.74	2	2
PCK1	-0.79	0.51	-9999	-1.1	41	41
HNF4A	-0.017	0.19	-9999	-0.73	2	2
KCNJ11	-0.035	0.21	-9999	-0.8	2	2
AKT1	-0.009	0.099	-9999	-10000	0	0
response to starvation	0.006	0.002	-9999	-10000	0	0
DLK1	-0.048	0.24	-9999	-0.88	3	3
NKX2-1	0.17	0.19	-9999	-0.49	1	1
ACADM	-0.09	0.34	-9999	-1.1	5	5
TAT	-0.31	0.23	-9999	-0.48	30	30
CEBPB	0.02	0.002	-9999	-10000	0	0
CEBPA	0.021	0.003	-9999	-10000	0	0
TTR	-0.28	0.22	-9999	-0.61	4	4
PKLR	-0.03	0.19	-9999	-0.74	2	2
APOA1	-0.027	0.21	-9999	-0.79	2	2
CPT1C	-0.044	0.19	-9999	-0.77	2	2
ALAS1	-0.005	0.11	-9999	-10000	0	0
TFRC	-0.1	0.16	-9999	-10000	0	0
FOXF1	-0.027	0.067	-9999	-10000	0	0
NF1	0.024	0	-9999	-10000	0	0
HNF1A (dimer)	0.012	0.06	-9999	-10000	0	0
CPT1A	-0.03	0.19	-9999	-0.74	2	2
HMGCS1	-0.031	0.19	-9999	-0.74	2	2
NR3C1	-0.48	0.32	-9999	-0.68	39	39
CPT1B	-0.03	0.19	-9999	-0.74	2	2
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.022	0.007	-9999	-10000	0	0
GCK	-0.03	0.19	-9999	-0.74	2	2
CREB1	-0.14	0.099	-9999	-10000	0	0
IGFBP1	-0.21	0.19	-9999	-0.64	4	4
PDX1	0.005	0.1	-9999	-10000	0	0
UCP2	-0.031	0.19	-9999	-0.74	2	2
ALDOB	-0.035	0.21	-9999	-0.8	2	2
AFP	-0.28	0.19	-9999	-0.43	31	31
BDH1	-0.03	0.19	-9999	-0.74	2	2
HADH	-0.059	0.29	-9999	-1.1	3	3
F2	-0.027	0.21	-9999	-0.79	2	2
HNF1A	0.012	0.06	-9999	-10000	0	0
G6PC	-0.092	0.095	-9999	-10000	0	0
SLC2A2	-0.003	0.13	-9999	-10000	0	0
INS	0	0.001	-9999	-10000	0	0
FOXA1	-0.44	0.34	-9999	-0.68	36	36
FOXA3	-0.16	0.12	-9999	-0.35	10	10
FOXA2	-0.041	0.25	-9999	-0.92	2	2
ABCC8	-0.1	0.35	-9999	-1	6	6
ALB	-0.28	0.19	-9999	-0.45	25	25

×

PDGFR-alpha signaling pathway

Figure S18. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S18. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.067	0.21	-9999	-0.72	5	5
PDGF/PDGFRA/CRKL	-0.035	0.16	-9999	-0.52	5	5
positive regulation of JUN kinase activity	-0.008	0.12	-9999	-0.39	5	5
CRKL	0.016	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.035	0.16	-9999	-0.52	5	5
AP1	-0.51	0.51	-9999	-1	26	26
mol:IP3	-0.053	0.16	-9999	-0.55	5	5
PLCG1	-0.053	0.16	-9999	-0.55	5	5
PDGF/PDGFRA/alphaV Integrin	-0.035	0.16	-9999	-0.52	5	5
RAPGEF1	0.016	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
mol:Ca2+	-0.053	0.16	-9999	-0.55	5	5
CAV3	0.016	0	-9999	-10000	0	0
CAV1	-0.51	0.31	-9999	-0.69	40	40
SHC/Grb2/SOS1	-0.007	0.12	-9999	-0.39	5	5
PDGF/PDGFRA/Shf	-0.037	0.16	-9999	-0.52	5	5
FOS	-0.48	0.52	-9999	-1	26	26
JUN	-0.041	0.073	-9999	-0.52	1	1
oligodendrocyte development	-0.035	0.16	-9999	-0.52	5	5
GRB2	0.016	0	-9999	-10000	0	0
PIK3R1	0.002	0.095	-9999	-0.69	1	1
mol:DAG	-0.053	0.16	-9999	-0.55	5	5
PDGF/PDGFRA	-0.067	0.21	-9999	-0.72	5	5
actin cytoskeleton reorganization	-0.035	0.16	-9999	-0.52	5	5
SRF	0.036	0.013	-9999	-10000	0	0
SHC1	0.016	0	-9999	-10000	0	0
PI3K	-0.035	0.17	-9999	-0.5	6	6
PDGF/PDGFRA/Crk/C3G	-0.019	0.13	-9999	-0.44	5	5
JAK1	-0.034	0.16	-9999	-0.52	5	5
ELK1/SRF	-0.007	0.13	-9999	-0.4	5	5
SHB	0.016	0	-9999	-10000	0	0
SHF	0.013	0.022	-9999	-10000	0	0
CSNK2A1	0.032	0.03	-9999	-10000	0	0
GO:0007205	-0.057	0.17	-9999	-0.57	5	5
SOS1	0.016	0	-9999	-10000	0	0
Ras protein signal transduction	-0.008	0.12	-9999	-0.39	5	5
PDGF/PDGFRA/SHB	-0.035	0.16	-9999	-0.52	5	5
PDGF/PDGFRA/Caveolin-1	-0.43	0.26	-9999	-0.56	42	42
ITGAV	0.016	0	-9999	-10000	0	0
ELK1	-0.06	0.15	-9999	-0.51	5	5
PIK3CA	0.002	0.095	-9999	-0.69	1	1
PDGF/PDGFRA/Crk	-0.035	0.16	-9999	-0.52	5	5
JAK-STAT cascade	-0.034	0.16	-9999	-0.52	5	5
cell proliferation	-0.037	0.16	-9999	-0.52	5	5

×

Integrins in angiogenesis

Figure S19. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S19. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.021	0.052	-9999	-10000	0	0
alphaV beta3 Integrin	-0.3	0.21	-9999	-0.44	38	38
PTK2	-0.12	0.12	-9999	-10000	0	0
IGF1R	0.016	0	-9999	-10000	0	0
PI4KB	0.016	0	-9999	-10000	0	0
MFGE8	0.002	0.095	-9999	-0.69	1	1
SRC	0.016	0	-9999	-10000	0	0
CDKN1B	-0.15	0.21	-9999	-0.85	4	4
VEGFA	-0.054	0.081	-9999	-10000	0	0
ILK	-0.1	0.085	-9999	-10000	0	0
ROCK1	0.016	0	-9999	-10000	0	0
AKT1	-0.083	0.078	-9999	-10000	0	0
PTK2B	0.009	0.038	-9999	-10000	0	0
alphaV/beta3 Integrin/JAM-A	-0.24	0.19	-9999	-0.36	38	38
CBL	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.027	0.02	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.17	0.26	-9999	-0.46	23	23
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.034	0.017	-9999	-10000	0	0
alphaV/beta3 Integrin/Syndecan-1	0.027	0.02	-9999	-10000	0	0
PI4KA	0.016	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.4	0.28	-9999	-0.72	19	19
PI4 Kinase	0.023	0	-9999	-10000	0	0
PIK3CA	0.002	0.095	-9999	-0.69	1	1
alphaV/beta3 Integrin/Osteopontin	-0.01	0.046	-9999	-10000	0	0
RPS6KB1	-0.36	0.27	-9999	-0.66	19	19
TLN1	0.016	0	-9999	-10000	0	0
MAPK3	-0.43	0.31	-9999	-0.61	38	38
GPR124	-0.011	0.13	-9999	-0.69	2	2
MAPK1	-0.43	0.31	-9999	-0.61	38	38
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.002	0.095	-9999	-0.69	1	1
alphaV/beta3 Integrin/Tumstatin	0.025	0.023	-9999	-10000	0	0
cell adhesion	-0.014	0.063	-9999	-0.33	2	2
ANGPTL3	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	-0.005	0.043	-9999	-10000	0	0
IGF-1R heterotetramer	0.016	0	-9999	-10000	0	0
Rac1/GDP	0.012	0	-9999	-10000	0	0
TGFBR2	0.016	0	-9999	-10000	0	0
ITGB3	0.006	0.037	-9999	-10000	0	0
IGF1	-0.26	0.34	-9999	-0.69	21	21
RAC1	0.016	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	0.009	0.089	-9999	-0.43	2	2
apoptosis	0.015	0	-9999	-10000	0	0
CD47	0.002	0.095	-9999	-0.69	1	1
alphaV/beta3 Integrin/CD47	0.018	0.065	-9999	-0.44	1	1
VCL	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.077	0.19	-9999	-0.44	12	12
CSF1	0.016	0	-9999	-10000	0	0
PIK3C2A	-0.1	0.085	-9999	-10000	0	0
PI4 Kinase/Pyk2	-0.22	0.15	-9999	-0.41	1	1
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.002	0.042	-9999	-10000	0	0
FAK1/Vinculin	-0.096	0.1	-9999	-10000	0	0
alphaV beta3/Integrin/ppsTEM5	0.01	0.089	-9999	-0.44	2	2
RHOA	0.016	0	-9999	-10000	0	0
VTN	0.016	0	-9999	-10000	0	0
BCAR1	0.016	0	-9999	-10000	0	0
FGF2	-0.48	0.32	-9999	-0.69	38	38
F11R	-0.36	0.25	-9999	-0.52	38	38
alphaV/beta3 Integrin/Lactadherin	0.018	0.065	-9999	-0.44	1	1
alphaV/beta3 Integrin/TGFBR2	0.027	0.02	-9999	-10000	0	0
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.04	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	0.026	0.018	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.01	0.031	-9999	-10000	0	0
alphaV/beta3 Integrin/Pyk2	0.013	0.039	-9999	-10000	0	0
SDC1	0.016	0	-9999	-10000	0	0
VAV3	0.014	0.11	-9999	-0.36	4	4
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	-0.063	0.22	-9999	-0.69	6	6
FAK1/Paxillin	-0.096	0.1	-9999	-10000	0	0
cell migration	-0.082	0.097	-9999	-10000	0	0
ITGAV	0.016	0	-9999	-10000	0	0
PI3K	-0.24	0.16	-9999	-0.33	39	39
SPP1	-0.054	0.081	-9999	-10000	0	0
KDR	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.016	0	-9999	-10000	0	0
COL4A3	0.013	0.022	-9999	-10000	0	0
angiogenesis	-0.42	0.3	-9999	-0.6	38	38
Rac1/GTP	0.021	0.098	-9999	-0.33	4	4
EDIL3	-0.14	0.29	-9999	-0.69	12	12
cell proliferation	0.027	0.02	-9999	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

Figure S20. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S20. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.017	0.024	-9999	-10000	0	0
AKT1	-0.16	0.26	-9999	-0.55	13	13
PTK2B	-0.086	0.16	-9999	-0.5	4	4
VEGFR2 homodimer/Frs2	-0.047	0.15	-9999	-0.49	5	5
CAV1	-0.51	0.31	-9999	-0.69	40	40
CALM1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.1	0.18	-9999	-0.56	4	4
endothelial cell proliferation	-0.14	0.24	-9999	-0.5	13	13
mol:Ca2+	-0.24	0.3	-9999	-0.72	12	12
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.088	0.17	-9999	-0.53	4	4
RP11-342D11.1	-0.25	0.3	-9999	-0.72	12	12
CDH5	0.002	0.095	-9999	-0.69	1	1
VEGFA homodimer	-0.01	0.049	-9999	-10000	0	0
SHC1	0.016	0	-9999	-10000	0	0
SHC2	-0.014	0.13	-9999	-0.69	2	2
HRAS/GDP	-0.22	0.24	-9999	-0.61	12	12
SH2D2A	0.003	0.043	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.18	0.22	-9999	-0.52	12	12
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.11	0.18	-9999	-0.56	4	4
VEGFR1 homodimer	0.002	0.095	-9999	-0.69	1	1
SHC/GRB2/SOS1	-0.24	0.28	-9999	-0.68	12	12
GRB10	-0.26	0.35	-9999	-0.81	12	12
PTPN11	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
PAK1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.084	0.18	-9999	-0.52	5	5
HRAS	0.016	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.027	0.092	-9999	-0.27	3	3
HIF1A	0.016	0	-9999	-10000	0	0
FRS2	0.016	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.088	0.17	-9999	-0.52	4	4
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.016	0	-9999	-10000	0	0
Nck/Pak	0.013	0.072	-9999	-0.51	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.1	0.18	-9999	-0.56	4	4
mol:GDP	-0.23	0.26	-9999	-0.66	12	12
mol:NADP	-0.14	0.21	-9999	-0.46	12	12
eNOS/Hsp90	-0.12	0.2	-9999	-0.43	12	12
PIK3R1	0.002	0.095	-9999	-0.69	1	1
mol:IP3	-0.25	0.31	-9999	-0.73	12	12
HIF1A/ARNT	0.023	0	-9999	-10000	0	0
SHB	0.016	0	-9999	-10000	0	0
VEGFA	-0.088	0.096	-9999	-10000	0	0
VEGFC	0.002	0.095	-9999	-0.69	1	1
FAK1/Vinculin	-0.055	0.15	-9999	-0.46	4	4
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.092	0.17	-9999	-0.53	4	4
PTPN6	0.016	0	-9999	-10000	0	0
EPAS1	-0.068	0.21	-9999	-0.72	5	5
mol:L-citrulline	-0.14	0.21	-9999	-0.46	12	12
ITGAV	0.016	0	-9999	-10000	0	0
PIK3CA	0.002	0.095	-9999	-0.69	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.088	0.17	-9999	-0.53	4	4
VEGFR2 homodimer/VEGFA homodimer	-0.27	0.34	-9999	-0.79	12	12
VEGFR2/3 heterodimer	-0.047	0.15	-9999	-0.49	5	5
VEGFB	0.016	0	-9999	-10000	0	0
MAPK11	-0.25	0.32	-9999	-0.74	12	12
VEGFR2 homodimer	-0.066	0.17	-9999	-0.57	5	5
FLT1	0.002	0.095	-9999	-0.69	1	1
NEDD4	-0.11	0.25	-9999	-0.76	7	7
MAPK3	-0.22	0.28	-9999	-0.66	12	12
MAPK1	-0.22	0.28	-9999	-0.66	12	12
VEGFA145/NRP2	-0.048	0.066	-9999	-10000	0	0
VEGFR1/2 heterodimer	-0.055	0.16	-9999	-0.5	6	6
KDR	-0.066	0.17	-9999	-0.57	5	5
VEGFA165/NRP1/VEGFR2 homodimer	-0.24	0.31	-9999	-0.72	12	12
SRC	0.016	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.22	0.29	-9999	-0.67	12	12
PI3K	-0.21	0.31	-9999	-0.69	13	13
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.11	0.19	-9999	-0.57	5	5
FES	-0.25	0.32	-9999	-0.74	12	12
GAB1	-0.18	0.22	-9999	-0.61	8	8
VEGFR2 homodimer/VEGFA homodimer/Src	-0.1	0.18	-9999	-0.52	5	5
CTNNB1	0.016	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
ARNT	0.016	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.34	0.25	-9999	-0.55	27	27
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.1	0.18	-9999	-0.56	4	4
PI3K/GAB1	-0.16	0.27	-9999	-0.56	13	13
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.084	0.17	-9999	-0.51	5	5
PRKACA	0.016	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.04	0.15	-9999	-0.44	6	6
HSP90AA1	0.016	0	-9999	-10000	0	0
CDC42	-0.25	0.32	-9999	-0.74	12	12
actin cytoskeleton reorganization	-0.11	0.18	-9999	-0.56	4	4
PTK2	-0.066	0.16	-9999	-0.5	4	4
EDG1	-0.48	0.47	-9999	-0.86	31	31
mol:DAG	-0.25	0.31	-9999	-0.73	12	12
CaM/Ca2+	-0.22	0.28	-9999	-0.67	12	12
MAP2K3	-0.23	0.3	-9999	-0.7	12	12
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.27	0.37	-9999	-0.84	12	12
PLCG1	-0.25	0.32	-9999	-0.74	12	12
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.088	0.17	-9999	-0.53	4	4
IQGAP1	0.016	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.1	0.18	-9999	-0.56	4	4
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.1	0.18	-9999	-0.56	4	4
cell migration	-0.022	0.14	-9999	-0.43	1	1
mol:PI-3-4-5-P3	-0.19	0.28	-9999	-0.62	13	13
FYN	0.016	0	-9999	-10000	0	0
VEGFB/NRP1	-0.23	0.29	-9999	-0.68	12	12
mol:NO	-0.14	0.21	-9999	-0.46	12	12
PXN	0.016	0	-9999	-10000	0	0
HRAS/GTP	-0.22	0.24	-9999	-0.61	12	12
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.26	0.36	-9999	-0.83	12	12
VHL	0.016	0	-9999	-10000	0	0
ITGB3	0.006	0.037	-9999	-10000	0	0
NOS3	-0.16	0.24	-9999	-0.52	12	12
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.12	0.2	-9999	-0.55	7	7
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	-0.22	0.29	-9999	-0.67	12	12
PRKCB	-0.23	0.29	-9999	-0.68	12	12
VCL	0.016	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.25	0.31	-9999	-0.73	12	12
VEGFR1/2 heterodimer/VEGFA homodimer	-0.11	0.19	-9999	-0.58	5	5
VEGFA165/NRP2	-0.048	0.066	-9999	-10000	0	0
MAPKKK cascade	-0.19	0.3	-9999	-0.67	12	12
NRP2	0.01	0.031	-9999	-10000	0	0
VEGFC homodimer	0.002	0.095	-9999	-0.69	1	1
NCK1	0.002	0.095	-9999	-0.69	1	1
ROCK1	0.016	0	-9999	-10000	0	0
FAK1/Paxillin	-0.055	0.15	-9999	-0.46	4	4
MAP3K13	-0.25	0.32	-9999	-0.74	12	12
PDPK1	-0.17	0.25	-9999	-0.55	13	13

×

IL23-mediated signaling events

Figure S21. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S21. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.15	0.42	-9999	-1	6	6
IL23A	-0.14	0.37	-9999	-0.84	5	5
NF kappa B1 p50/RelA/I kappa B alpha	-0.18	0.28	-9999	-0.63	12	12
positive regulation of T cell mediated cytotoxicity	-0.14	0.37	-9999	-0.7	12	12
ITGA3	-0.12	0.34	-9999	-0.85	3	3
IL17F	-0.058	0.28	-9999	-0.64	3	3
IL12B	0.022	0.026	-9999	-10000	0	0
STAT1 (dimer)	-0.14	0.36	-9999	-0.7	10	10
CD4	-0.12	0.34	-9999	-0.74	5	5
IL23	-0.14	0.35	-9999	-0.82	5	5
IL23R	0.006	0.086	-9999	-10000	0	0
IL1B	-0.15	0.4	-9999	-0.9	6	6
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.12	0.34	-9999	-0.82	3	3
TYK2	0.014	0.021	-9999	-10000	0	0
STAT4	0.016	0	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
IL18RAP	-0.11	0.27	-9999	-0.69	10	10
IL12RB1	0.014	0.021	-9999	-10000	0	0
PIK3CA	0.003	0.095	-9999	-0.69	1	1
IL12Rbeta1/TYK2	0.017	0.028	-9999	-10000	0	0
IL23R/JAK2	0.009	0.11	-9999	-10000	0	0
positive regulation of chronic inflammatory response	-0.14	0.37	-9999	-0.7	12	12
natural killer cell activation	0	0.007	-9999	-10000	0	0
JAK2	0.022	0.026	-9999	-10000	0	0
PIK3R1	0.003	0.095	-9999	-0.69	1	1
NFKB1	0.015	0.004	-9999	-10000	0	0
RELA	0.015	0.004	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.13	0.34	-9999	-0.78	5	5
ALOX12B	-0.12	0.34	-9999	-0.74	5	5
CXCL1	-0.2	0.45	-9999	-0.97	9	9
T cell proliferation	-0.14	0.37	-9999	-0.7	12	12
NFKBIA	0.015	0.004	-9999	-10000	0	0
IL17A	-0.024	0.24	-9999	-0.52	2	2
PI3K	-0.18	0.33	-9999	-0.69	12	12
IFNG	-0.008	0.032	-9999	-10000	0	0
STAT3 (dimer)	-0.17	0.31	-9999	-0.72	8	8
IL18R1	0.017	0.002	-9999	-10000	0	0
IL23/IL23R/JAK2/TYK2/SOCS3	-0.05	0.23	-9999	-0.47	2	2
IL18/IL18R	-0.05	0.18	-9999	-0.43	10	10
macrophage activation	-0.014	0.015	-9999	-0.038	8	8
TNF	-0.14	0.36	-9999	-0.8	5	5
STAT3/STAT4	-0.18	0.29	-9999	-0.64	12	12
STAT4 (dimer)	-0.13	0.36	-9999	-0.67	12	12
IL18	0.017	0.002	-9999	-10000	0	0
IL19	-0.14	0.34	-9999	-0.76	5	5
STAT5A (dimer)	-0.13	0.36	-9999	-0.67	12	12
STAT1	0.006	0.037	-9999	-10000	0	0
SOCS3	0.013	0.022	-9999	-10000	0	0
CXCL9	-0.33	0.58	-9999	-1.1	17	17
MPO	-0.12	0.34	-9999	-0.78	4	4
positive regulation of humoral immune response	-0.14	0.37	-9999	-0.7	12	12
IL23/IL23R/JAK2/TYK2	-0.14	0.38	-9999	-0.72	12	12
IL6	-0.35	0.62	-9999	-1.2	18	18
STAT5A	0.016	0	-9999	-10000	0	0
IL2	0.018	0.007	-9999	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0.007	-9999	-10000	0	0
CD3E	-0.12	0.34	-9999	-0.82	3	3
keratinocyte proliferation	-0.14	0.37	-9999	-0.7	12	12
NOS2	-0.13	0.34	-9999	-0.64	12	12

×

Signaling events mediated by PRL

Figure S22. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S22. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.066	0.081	-9999	-10000	0	0
mol:Halofuginone	0.004	0.002	-9999	-10000	0	0
ITGA1	0.013	0.022	-9999	-10000	0	0
CDKN1A	-0.056	0.091	-9999	-10000	0	0
PRL-3/alpha Tubulin	0.012	0.033	-9999	-10000	0	0
mol:Ca2+	-0.009	0.078	-9999	-0.53	1	1
AGT	-0.007	0.1	-9999	-0.69	1	1
CCNA2	-0.18	0.2	-9999	-0.37	28	28
TUBA1B	0.016	0	-9999	-10000	0	0
EGR1	-0.25	0.27	-9999	-0.51	28	28
CDK2/Cyclin E1	-0.059	0.097	-9999	-10000	0	0
MAPK3	0.014	0.034	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0.023	0	-9999	-10000	0	0
MAPK1	0.014	0.034	-9999	-10000	0	0
PTP4A1	-0.18	0.21	-9999	-0.38	28	28
PTP4A3	-0.003	0.051	-9999	-10000	0	0
PTP4A2	0.016	0	-9999	-10000	0	0
ITGB1	0.014	0.034	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
RAC1	-0.059	0.09	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.023	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.16	0.2	-9999	-0.35	28	28
RABGGTA	0.016	0	-9999	-10000	0	0
BCAR1	0.007	0.021	-9999	-10000	0	0
RHOC	-0.059	0.09	-9999	-10000	0	0
RHOA	-0.059	0.09	-9999	-10000	0	0
cell motility	-0.061	0.097	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.16	0.2	-9999	-0.35	28	28
PRL-3/alpha1 Integrin	0.01	0.035	-9999	-10000	0	0
ROCK1	-0.061	0.097	-9999	-10000	0	0
RABGGTB	0.016	0	-9999	-10000	0	0
CDK2	0.006	0.037	-9999	-10000	0	0
mitosis	-0.18	0.21	-9999	-0.38	28	28
ATF5	0.006	0.037	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

Figure S23. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S23. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.13	0.2	-9999	-0.34	26	26
MAP3K8	-0.041	0.18	-9999	-0.69	4	4
FOS	-0.065	0.12	-9999	-0.3	2	2
PRKCA	0.009	0.008	-9999	-10000	0	0
PTPN7	0.009	0.009	-9999	-10000	0	0
HRAS	0.014	0.002	-9999	-10000	0	0
PRKCB	-0.008	0.01	-9999	-0.019	26	26
NRAS	0.011	0.022	-9999	-10000	0	0
RAS family/GTP	0.015	0.018	-9999	-10000	0	0
MAPK3	-0.023	0.064	-9999	-10000	0	0
MAP2K1	-0.022	0.074	-9999	-0.26	2	2
ELK1	0.004	0.013	-9999	-10000	0	0
BRAF	-0.013	0.015	-9999	-10000	0	0
mol:GTP	-0.003	0.003	-9999	-0.006	26	26
MAPK1	-0.023	0.064	-9999	-10000	0	0
RAF1	-0.014	0.018	-9999	-10000	0	0
KRAS	0.014	0.002	-9999	-10000	0	0

×

Signaling events mediated by the Hedgehog family

Figure S24. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S24. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.036	0.082	-10000	0	-0.51	1	1
IHH	-0.054	0.071	-10000	0	-10000	0	0
SHH Np/Cholesterol/GAS1	-0.33	0.19	-10000	0	-0.42	43	43
LRPAP1	0.016	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.32	0.19	0.41	43	-10000	0	43
SMO/beta Arrestin2	0.044	0.056	-10000	0	-10000	0	0
SMO	0.038	0.059	-10000	0	-10000	0	0
AKT1	0.037	0.059	-10000	0	-0.34	1	1
ARRB2	0.016	0	-10000	0	-10000	0	0
BOC	-0.05	0.2	-10000	0	-0.69	5	5
ADRBK1	0.016	0	-10000	0	-10000	0	0
heart looping	0.038	0.058	-10000	0	-10000	0	0
STIL	0.006	0.093	-10000	0	-0.37	1	1
DHH N/PTCH2	0.023	0	-10000	0	-10000	0	0
DHH N/PTCH1	0.034	0.043	-10000	0	-10000	0	0
PIK3CA	0.002	0.095	-10000	0	-0.69	1	1
DHH	0.016	0	-10000	0	-10000	0	0
PTHLH	0.032	0.14	-10000	0	-1	1	1
determination of left/right symmetry	0.038	0.058	-10000	0	-10000	0	0
PIK3R1	0.002	0.095	-10000	0	-0.69	1	1
skeletal system development	0.032	0.14	-10000	0	-0.99	1	1
IHH N/Hhip	-0.048	0.07	-10000	0	-10000	0	0
DHH N/Hhip	-0.01	0.049	-10000	0	-10000	0	0
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.038	0.058	-10000	0	-10000	0	0
pancreas development	-0.036	0.076	-10000	0	-10000	0	0
HHAT	-0.024	0.16	-10000	0	-0.69	3	3
PI3K	0.005	0.13	-10000	0	-0.94	1	1
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.53	0.29	-10000	0	-0.69	42	42
somite specification	0.038	0.058	-10000	0	-10000	0	0
SHH Np/Cholesterol/PTCH1	0.017	0.098	-10000	0	-0.36	3	3
SHH Np/Cholesterol/PTCH2	0.004	0.097	-10000	0	-0.4	3	3
SHH Np/Cholesterol/Megalin	-0.083	0.19	-10000	0	-0.4	14	14
SHH	-0.004	0.12	-10000	0	-0.51	3	3
catabolic process	0.028	0.049	-10000	0	-10000	0	0
SMO/Vitamin D3	0.035	0.1	-10000	0	-0.41	1	1
SHH Np/Cholesterol/Hhip	-0.02	0.098	-10000	0	-0.4	3	3
LRP2	-0.13	0.28	-10000	0	-0.69	11	11
receptor-mediated endocytosis	-0.028	0.15	-10000	0	-0.47	2	2
SHH Np/Cholesterol/BOC	-0.035	0.15	-10000	0	-0.4	8	8
SHH Np/Cholesterol/CDO	0.004	0.097	-10000	0	-0.4	3	3
mesenchymal cell differentiation	0.02	0.097	0.4	3	-10000	0	3
mol:Vitamin D3	0.03	0.1	-10000	0	-0.35	3	3
IHH N/PTCH2	-0.01	0.035	-10000	0	-10000	0	0
CDON	0.016	0	-10000	0	-10000	0	0
IHH N/PTCH1	0.051	0.052	-10000	0	-10000	0	0
Megalin/LRPAP1	-0.086	0.22	-10000	0	-0.51	11	11
PTCH2	0.016	0	-10000	0	-10000	0	0
SHH Np/Cholesterol	-0.006	0.097	-10000	0	-0.41	3	3
PTCH1	0.028	0.049	-10000	0	-10000	0	0
HHIP	-0.036	0.076	-10000	0	-10000	0	0

×

Glypican 1 network

Figure S25. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S25. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.3	0.22	-9999	-0.44	38	38
fibroblast growth factor receptor signaling pathway	-0.3	0.22	-9999	-0.44	38	38
LAMA1	-0.009	0.058	-9999	-10000	0	0
PRNP	0.002	0.095	-9999	-0.69	1	1
GPC1/SLIT2	-0.052	0.18	-9999	-0.51	7	7
SMAD2	0.036	0.01	-9999	-10000	0	0
GPC1/PrPc/Cu2+	0.011	0.064	-9999	-0.44	1	1
GPC1/Laminin alpha1	0.006	0.039	-9999	-10000	0	0
TDGF1	-0.009	0.058	-9999	-10000	0	0
CRIPTO/GPC1	0.006	0.039	-9999	-10000	0	0
APP/GPC1	0.021	0.014	-9999	-10000	0	0
mol:NO	0	0	-9999	-10000	0	0
YES1	0.017	0.032	-9999	-10000	0	0
FLT1	0.002	0.095	-9999	-0.69	1	1
GPC1/TGFB/TGFBR1/TGFBR2	0.03	0.012	-9999	-10000	0	0
SERPINC1	0.016	0	-9999	-10000	0	0
FYN	0.017	0.032	-9999	-10000	0	0
FGR	0.017	0.032	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.043	0.035	-9999	-10000	0	0
SLIT2	-0.082	0.24	-9999	-0.69	7	7
GPC1/NRG	0.021	0.014	-9999	-10000	0	0
NRG1	0.016	0	-9999	-10000	0	0
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.015	0.074	-9999	-0.44	1	1
LYN	0.015	0.037	-9999	-10000	0	0
mol:Spermine	0.011	0.014	-9999	-10000	0	0
cell growth	-0.3	0.22	-9999	-0.44	38	38
BMP signaling pathway	-0.013	0.022	-9999	-10000	0	0
SRC	0.017	0.032	-9999	-10000	0	0
TGFBR1	0.016	0	-9999	-10000	0	0
mol:Cu2+	0	0	-9999	-10000	0	0
PLA2G2A	-0.36	0.35	-9999	-0.69	29	29
GPC1	0.013	0.022	-9999	-10000	0	0
TGFBR1 (dimer)	0.016	0	-9999	-10000	0	0
VEGFA	-0.054	0.081	-9999	-10000	0	0
BLK	0.015	0.034	-9999	-10000	0	0
HCK	0.008	0.069	-9999	-0.44	1	1
FGF2	-0.48	0.32	-9999	-0.69	38	38
FGFR1	0.013	0.022	-9999	-10000	0	0
VEGFR1 homodimer	0.002	0.095	-9999	-0.69	1	1
TGFBR2	0.016	0	-9999	-10000	0	0
cell death	0.021	0.014	-9999	-10000	0	0
ATIII/GPC1	0.021	0.014	-9999	-10000	0	0
PLA2G2A/GPC1	-0.27	0.27	-9999	-0.51	29	29
LCK	0.014	0.035	-9999	-10000	0	0
neuron differentiation	0.021	0.014	-9999	-10000	0	0
PrPc/Cu2+	0.002	0.072	-9999	-0.52	1	1
APP	0.016	0	-9999	-10000	0	0
TGFBR2 (dimer)	0.016	0	-9999	-10000	0	0

×

Insulin Pathway

Figure S26. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S26. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.28	0.21	-9999	-0.4	38	38
TC10/GTP	-0.24	0.15	-9999	-0.33	38	38
Insulin Receptor/Insulin/IRS1/Shp2	-0.006	0.14	-9999	-0.4	6	6
HRAS	0.016	0	-9999	-10000	0	0
APS homodimer	0	0	-9999	-10000	0	0
GRB14	-0.022	0.11	-9999	-0.69	1	1
FOXO3	-0.008	0.023	-9999	-10000	0	0
AKT1	-0.003	0.15	-9999	-0.42	3	3
INSR	0.018	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0.051	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	-0.024	0.16	-9999	-0.69	3	3
SORBS1	-0.48	0.32	-9999	-0.69	38	38
CRK	0.016	0	-9999	-10000	0	0
PTPN1	0.045	0	-9999	-10000	0	0
CAV1	-0.31	0.22	-9999	-0.42	41	41
CBL/APS/CAP/Crk-II/C3G	-0.25	0.19	-9999	-0.37	38	38
Insulin Receptor/Insulin/IRS1/NCK2	-0.006	0.14	-9999	-0.4	6	6
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.051	0.14	-9999	-0.4	7	7
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.02	0.086	-9999	-10000	0	0
RPS6KB1	0.006	0.14	-9999	-0.53	1	1
PARD6A	0.013	0.022	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0.006	0.025	-9999	-10000	0	0
PIK3R1	0.002	0.095	-9999	-0.69	1	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.044	0.12	-9999	-0.52	1	1
HRAS/GTP	-0.033	0.093	-9999	-0.3	6	6
Insulin Receptor	0.018	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.003	0.13	-9999	-0.37	6	6
PRKCI	-0.009	0.031	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.053	0.14	-9999	-0.46	3	3
SHC1	0.016	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	-0.002	0.056	-9999	-0.38	1	1
PI3K	-0.052	0.14	-9999	-0.4	7	7
NCK2	0.016	0	-9999	-10000	0	0
RHOQ	0.016	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0.012	0	-9999	-10000	0	0
AKT2	-0.003	0.15	-9999	-0.42	3	3
PRKCZ	-0.012	0.033	-9999	-10000	0	0
SH2B2	0	0	-9999	-10000	0	0
SHC/SHIP	-0.008	0.12	-9999	-0.35	6	6
F2RL2	0.016	0	-9999	-10000	0	0
TRIP10	0.013	0.022	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0.033	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.02	0.012	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.049	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
NCK1	0.002	0.095	-9999	-0.69	1	1
CBL/APS/CAP/Crk-II	-0.27	0.2	-9999	-0.4	38	38
TC10/GDP	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.018	0.1	-9999	-0.4	3	3
INPP5D	-0.018	0.13	-9999	-0.38	6	6
SOS1	0.016	0	-9999	-10000	0	0
SGK1	-0.005	0.012	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	-0.063	0.22	-9999	-0.69	6	6
p62DOK/RasGAP	-0.002	0.056	-9999	-0.38	1	1
INS	0.018	0	-9999	-10000	0	0
mol:PI-3-4-P2	-0.018	0.13	-9999	-0.38	6	6
GRB2	0.016	0	-9999	-10000	0	0
EIF4EBP1	0.004	0.14	-9999	-0.58	1	1
PTPRA	0.018	0	-9999	-10000	0	0
PIK3CA	0.002	0.095	-9999	-0.69	1	1
TC10/GTP/CIP4	0.02	0.012	-9999	-10000	0	0
PDPK1	0.016	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.01	0.099	-9999	-0.27	6	6
Insulin Receptor/Insulin/IRS1	-0.016	0.14	-9999	-0.41	6	6
Insulin Receptor/Insulin/IRS3	0.026	0	-9999	-10000	0	0
Par3/Par6	0.034	0.014	-9999	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

Figure S27. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S27. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.02	0.012	-10000	0	-10000	0	0
HSPA8	0.014	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.056	0.15	-10000	0	-0.48	6	6
AKT1	0.019	0	-10000	0	-10000	0	0
GSC	-0.18	0.48	-10000	0	-1.3	8	8
NKX2-5	-0.015	0.062	-10000	0	-10000	0	0
muscle cell differentiation	0.073	0.13	0.34	3	-10000	0	3
SMAD2-3/SMAD4/SP1	0.043	0.07	-10000	0	-10000	0	0
SMAD4	-0.003	0.05	-10000	0	-10000	0	0
CBFB	0.016	0	-10000	0	-10000	0	0
SAP18	0.015	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.005	0.13	-10000	0	-0.44	4	4
SMAD3/SMAD4/VDR	0.003	0.075	-10000	0	-0.37	1	1
MYC	0.012	0	-10000	0	-10000	0	0
CDKN2B	0.028	0.03	-10000	0	-10000	0	0
AP1	-0.13	0.21	-10000	0	-0.38	9	9
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.046	0.046	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.028	0.035	-10000	0	-10000	0	0
SP3	0.019	0	-10000	0	-10000	0	0
CREB1	0.016	0	-10000	0	-10000	0	0
FOXH1	-0.014	0.059	-10000	0	-10000	0	0
SMAD3/SMAD4/GR	-0.34	0.21	-10000	0	-0.47	39	39
GATA3	-0.62	0.18	-10000	0	-0.67	50	50
SKI/SIN3/HDAC complex/NCoR1	0.046	0.019	-10000	0	-10000	0	0
MEF2C/TIF2	-0.14	0.34	-10000	0	-0.7	14	14
endothelial cell migration	-0.11	0.061	-10000	0	-10000	0	0
MAX	0.013	0.002	-10000	0	-10000	0	0
RBBP7	0.006	0.037	-10000	0	-10000	0	0
RBBP4	0.015	0.001	-10000	0	-10000	0	0
RUNX2	0.016	0	-10000	0	-10000	0	0
RUNX3	-0.037	0.18	-10000	0	-0.69	4	4
RUNX1	-0.024	0.16	-10000	0	-0.69	3	3
CTBP1	0.016	0	-10000	0	-10000	0	0
NR3C1	-0.5	0.32	-10000	0	-0.69	39	39
VDR	-0.011	0.13	-10000	0	-0.69	2	2
CDKN1A	0.066	0.031	-10000	0	-10000	0	0
KAT2B	0.001	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.033	0.16	-10000	0	-0.41	6	6
DCP1A	0.016	0	-10000	0	-10000	0	0
SKI	0.015	0.001	-10000	0	-10000	0	0
SERPINE1	0.11	0.061	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF2	0.004	0.029	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.014	0.096	-10000	0	-0.48	2	2
SAP30	0.015	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.041	0.034	-10000	0	-10000	0	0
JUN	-0.13	0.2	-10000	0	-0.37	9	9
SMAD3/SMAD4/IRF7	0.007	0.03	-10000	0	-10000	0	0
TFE3	0.022	0.008	-10000	0	-10000	0	0
COL1A2	0.031	0.056	-10000	0	-10000	0	0
mesenchymal cell differentiation	-0.004	0.029	-10000	0	-10000	0	0
DLX1	0.01	0.031	-10000	0	-10000	0	0
TCF3	0.003	0.043	-10000	0	-10000	0	0
FOS	-0.32	0.35	-10000	0	-0.68	26	26
SMAD3/SMAD4/Max	0.003	0.029	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.027	0.064	-10000	0	-0.44	1	1
ZBTB17	0.013	0	-10000	0	-10000	0	0
LAMC1	0.039	0.045	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.004	0.029	-10000	0	-10000	0	0
IRF7	0.017	0.021	-10000	0	-10000	0	0
ESR1	-0.084	0.22	-10000	0	-0.69	6	6
HNF4A	0.016	0	-10000	0	-10000	0	0
MEF2C	-0.15	0.35	-10000	0	-0.74	14	14
SMAD2-3/SMAD4	0.002	0.074	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.038	0.018	-10000	0	-10000	0	0
IGHV3OR16-13	-0.01	0.032	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.016	0	-10000	0	-10000	0	0
CREBBP	0.019	0.008	-10000	0	-10000	0	0
SKIL	-0.004	0.099	-10000	0	-0.69	1	1
HDAC1	0.015	0.001	-10000	0	-10000	0	0
HDAC2	0.015	0.001	-10000	0	-10000	0	0
SNIP1	0.002	0.095	-10000	0	-0.69	1	1
GCN5L2	0.016	0.024	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.034	0.049	-10000	0	-10000	0	0
MSG1/HSC70	-0.02	0.14	-10000	0	-0.51	4	4
SMAD2	-0.009	0.058	-10000	0	-10000	0	0
SMAD3	0.02	0.026	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.031	0.046	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.003	0.03	-10000	0	-10000	0	0
NCOR1	0.015	0.001	-10000	0	-10000	0	0
NCOA2	0.016	0	-10000	0	-10000	0	0
NCOA1	0.016	0	-10000	0	-10000	0	0
MYOD/E2A	0.01	0.04	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.052	0.066	-10000	0	-10000	0	0
IFNB1	0.039	0.033	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	-0.15	0.34	-10000	0	-0.7	14	14
CITED1	-0.037	0.18	-10000	0	-0.69	4	4
SMAD2-3/SMAD4/ARC105	0.012	0.067	-10000	0	-10000	0	0
RBL1	0.016	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.056	0.029	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	-0.028	0.18	-10000	0	-0.5	6	6
SMAD7	-0.058	0.17	-10000	0	-10000	0	0
MYC/MIZ-1	0.016	0	-10000	0	-10000	0	0
SMAD3/SMAD4	0.038	0.088	0.3	2	-10000	0	2
IL10	-0.35	0.11	-10000	0	-0.4	32	32
PIASy/HDAC complex	0.01	0.022	-10000	0	-10000	0	0
PIAS3	0.014	0.023	-10000	0	-10000	0	0
CDK2	0.009	0.037	-10000	0	-10000	0	0
IL5	-0.35	0.11	-10000	0	-0.38	50	50
CDK4	0.019	0.009	-10000	0	-10000	0	0
PIAS4	0.01	0.023	-10000	0	-10000	0	0
ATF3	-0.011	0.13	-10000	0	-0.69	2	2
SMAD3/SMAD4/SP1	0.041	0.047	-10000	0	-10000	0	0
FOXG1	-0.095	0.077	-10000	0	-10000	0	0
FOXO3	0.031	0	-10000	0	-10000	0	0
FOXO1	0.031	0	-10000	0	-10000	0	0
FOXO4	0.031	0	-10000	0	-10000	0	0
heart looping	-0.15	0.35	-10000	0	-0.73	14	14
CEBPB	0.017	0	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.001	0.033	-10000	0	-10000	0	0
MYOD1	0.006	0.037	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	0.004	0.029	-10000	0	-10000	0	0
SMAD3/SMAD4/GATA3	-0.4	0.13	-10000	0	-0.44	50	50
SnoN/SIN3/HDAC complex/NCoR1	-0.004	0.099	-10000	0	-0.69	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.017	0.17	-10000	0	-0.45	6	6
SMAD3/SMAD4/SP1-3	0.052	0.048	-10000	0	-10000	0	0
MED15	0.016	0	-10000	0	-10000	0	0
SP1	0.028	0.001	-10000	0	-10000	0	0
SIN3B	0.015	0.001	-10000	0	-10000	0	0
SIN3A	0.015	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.06	0.21	-10000	0	-0.47	8	8
ITGB5	0.059	0.03	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.05	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.033	0.13	-10000	0	-0.47	4	4
AR	-0.037	0.18	-10000	0	-0.69	4	4
negative regulation of cell growth	0.025	0.058	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	0.002	0.034	-10000	0	-10000	0	0
E2F5	-0.01	0.1	-10000	0	-0.69	1	1
E2F4	0.016	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.004	0.12	-10000	0	-0.31	3	3
SMAD2-3/SMAD4/FOXO1-3a-4	0.049	0.032	-10000	0	-10000	0	0
TFDP1	0.013	0.022	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.12	0.21	-10000	0	-0.38	9	9
SMAD3/SMAD4/RUNX2	0.004	0.029	-10000	0	-10000	0	0
TGIF2	0.016	0	-10000	0	-10000	0	0
TGIF1	0.01	0.031	-10000	0	-10000	0	0
ATF2	0.016	0	-10000	0	-10000	0	0

×

IL12-mediated signaling events

Figure S28. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S28. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.014	0.068	-9999	-10000	0	0
TBX21	-0.21	0.53	-9999	-1.1	12	12
B2M	-0.009	0.13	-9999	-0.69	2	2
TYK2	0.01	0.019	-9999	-10000	0	0
IL12RB1	0.01	0.019	-9999	-10000	0	0
GADD45B	-0.094	0.31	-9999	-0.76	7	7
IL12RB2	0.009	0.02	-9999	-10000	0	0
GADD45G	-0.093	0.31	-9999	-0.76	7	7
natural killer cell activation	-0.006	0.023	-9999	-10000	0	0
RELB	0.016	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
IL18	0.018	0.006	-9999	-10000	0	0
IL2RA	0.016	0	-9999	-10000	0	0
IFNG	0.006	0.037	-9999	-10000	0	0
STAT3 (dimer)	-0.072	0.3	-9999	-0.66	9	9
HLA-DRB5	-0.007	0.097	-9999	-0.7	1	1
FASLG	-0.11	0.36	-9999	-0.76	11	11
NF kappa B2 p52/RelB	-0.18	0.32	-9999	-0.75	11	11
CD4	0.009	0.008	-9999	-10000	0	0
SOCS1	0.016	0	-9999	-10000	0	0
EntrezGene:6955	-0.01	0.014	-9999	-10000	0	0
CD3D	0.01	0.01	-9999	-10000	0	0
CD3E	0.01	0.009	-9999	-10000	0	0
CD3G	0.007	0.023	-9999	-10000	0	0
IL12Rbeta2/JAK2	0.013	0.033	-9999	-10000	0	0
CCL3	-0.11	0.36	-9999	-0.83	9	9
CCL4	-0.23	0.58	-9999	-1.4	10	10
HLA-A	0.011	0.031	-9999	-10000	0	0
IL18/IL18R	-0.032	0.2	-9999	-0.44	10	10
NOS2	-0.11	0.34	-9999	-0.68	12	12
IL12/IL12R/TYK2/JAK2/SPHK2	0.014	0.068	-9999	-10000	0	0
IL1R1	-0.14	0.44	-9999	-1	9	9
IL4	0.023	0.022	-9999	-10000	0	0
JAK2	0.01	0.019	-9999	-10000	0	0
EntrezGene:6957	-0.008	0.012	-9999	-10000	0	0
TCR/CD3/MHC I/CD8	0.004	0.071	-9999	-10000	0	0
RAB7A	-0.054	0.27	-9999	-0.7	5	5
lysosomal transport	-0.05	0.26	-9999	-0.66	5	5
FOS	-0.56	0.61	-9999	-1.1	27	27
STAT4 (dimer)	-0.079	0.32	-9999	-0.71	9	9
STAT5A (dimer)	-0.17	0.32	-9999	-0.75	11	11
GZMA	-0.12	0.36	-9999	-0.76	11	11
GZMB	-0.14	0.42	-9999	-0.97	9	9
HLX	0.016	0	-9999	-10000	0	0
LCK	-0.13	0.38	-9999	-0.81	11	11
TCR/CD3/MHC II/CD4	-0.085	0.14	-9999	-0.36	4	4
IL2/IL2R	0.04	0	-9999	-10000	0	0
MAPK14	-0.081	0.32	-9999	-0.69	9	9
CCR5	-0.12	0.38	-9999	-0.92	8	8
IL1B	-0.016	0.14	-9999	-0.73	2	2
STAT6	-0.025	0.12	-9999	-0.26	7	7
STAT4	0.016	0	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
STAT1	0.006	0.037	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
NFKB2	0.016	0	-9999	-10000	0	0
IL12B	0.009	0.02	-9999	-10000	0	0
CD8A	0.002	0.001	-9999	-10000	0	0
CD8B	0.008	0.037	-9999	-10000	0	0
T-helper 1 cell differentiation	0	0	-9999	-10000	0	0
natural killer cell mediated cytotoxicity	-0.014	0.068	-9999	-10000	0	0
IL2RB	0.016	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.069	0.3	-9999	-0.66	9	9
IL2RG	0.016	0	-9999	-10000	0	0
IL12	0.011	0.033	-9999	-10000	0	0
STAT5A	0.016	0	-9999	-10000	0	0
CD247	-0.029	0.16	-9999	-0.69	3	3
IL2	0.016	0	-9999	-10000	0	0
SPHK2	0.016	0	-9999	-10000	0	0
FRAP1	0.016	0	-9999	-10000	0	0
IL12A	0.007	0.026	-9999	-10000	0	0
IL12/IL12R/TYK2/JAK2	-0.14	0.41	-9999	-0.87	11	11
MAP2K3	-0.087	0.32	-9999	-0.7	9	9
RIPK2	0.013	0.022	-9999	-10000	0	0
MAP2K6	-0.088	0.32	-9999	-0.7	9	9
regulation of dendritic cell antigen processing and presentation	0	0	-9999	-10000	0	0
HLA-DRA	-0.043	0.18	-9999	-0.7	4	4
IL18RAP	-0.11	0.28	-9999	-0.69	10	10
IL12Rbeta1/TYK2	0.011	0.029	-9999	-10000	0	0
EOMES	0.022	0.037	-9999	-10000	0	0
STAT1 (dimer)	-0.073	0.29	-9999	-0.64	9	9
T cell proliferation	-0.06	0.25	-9999	-0.54	9	9
T-helper 1 cell lineage commitment	0	0	-9999	-10000	0	0
IL18R1	0.018	0.006	-9999	-10000	0	0
CD8-positive alpha-beta T cell lineage commitment	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.14	0.23	-9999	-0.59	9	9
ATF2	-0.067	0.3	-9999	-0.67	8	8

×

PLK2 and PLK4 events

Figure S29. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S29. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.05	0.2	-9999	-0.69	5	5
PLK4	-0.006	0.055	-9999	-10000	0	0
regulation of centriole replication	-0.038	0.16	-9999	-0.53	5	5

×

BMP receptor signaling

Figure S30. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S30. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.042	0.17	-9999	-0.39	10	10
SMAD6-7/SMURF1	0.03	0.012	-9999	-10000	0	0
NOG	-0.015	0.063	-9999	-10000	0	0
SMAD9	0.012	0.045	-9999	-10000	0	0
SMAD4	0.016	0	-9999	-10000	0	0
SMAD5	-0.001	0.079	-9999	-10000	0	0
BMP7/USAG1	-0.35	0.25	-9999	-0.54	35	35
SMAD5/SKI	0.007	0.076	-9999	-10000	0	0
SMAD1	0.029	0.061	-9999	-10000	0	0
BMP2	-0.053	0.2	-9999	-0.69	5	5
SMAD1/SMAD1/SMAD4	-0.006	0.034	-9999	-10000	0	0
BMPR1A	0.016	0	-9999	-10000	0	0
BMPR1B	-0.009	0.058	-9999	-10000	0	0
BMPR1A-1B/BAMBI	0.002	0.071	-9999	-0.44	1	1
AHSG	0.016	0	-9999	-10000	0	0
CER1	0.016	0	-9999	-10000	0	0
BMP2-4/CER1	-0.052	0.18	-9999	-0.44	9	9
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	0.006	0.1	-9999	-10000	0	0
BMP2-4 (homodimer)	-0.073	0.2	-9999	-0.52	9	9
RGMB	0.016	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.03	0.15	-9999	-0.4	7	7
RGMA	-0.011	0.13	-9999	-0.69	2	2
SMURF1	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.01	0.098	-9999	-10000	0	0
BMP2-4/USAG1	-0.35	0.27	-9999	-0.5	38	38
SMAD6/SMURF1/SMAD5	0.007	0.076	-9999	-10000	0	0
SOSTDC1	-0.44	0.34	-9999	-0.69	35	35
BMP7/BMPR2/BMPR1A-1B	0.003	0.042	-9999	-10000	0	0
SKI	0.016	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.082	0.24	-9999	-0.69	7	7
HFE2	0.016	0	-9999	-10000	0	0
ZFYVE16	0.016	0	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.052	0.18	-9999	-0.44	9	9
SMAD5/SMAD5/SMAD4	0.007	0.076	-9999	-10000	0	0
MAPK1	0.016	0	-9999	-10000	0	0
TAK1/TAB family	-0.021	0.064	-9999	-10000	0	0
BMP7 (homodimer)	-0.036	0.076	-9999	-10000	0	0
NUP214	0.016	0	-9999	-10000	0	0
BMP6/FETUA	-0.05	0.18	-9999	-0.51	7	7
SMAD1/SKI	0.036	0.059	-9999	-10000	0	0
SMAD6	0.013	0.022	-9999	-10000	0	0
CTDSP2	0.016	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.052	0.18	-9999	-0.44	9	9
MAP3K7IP1	0.016	0	-9999	-10000	0	0
GREM1	0.016	0	-9999	-10000	0	0
BMPR2 (homodimer)	0.016	0	-9999	-10000	0	0
GADD34/PP1CA	0.032	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	0.008	0.037	-9999	-10000	0	0
CHRDL1	-0.089	0.25	-9999	-0.69	8	8
ENDOFIN/SMAD1	0.036	0.059	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.001	0.045	-9999	-10000	0	0
SMAD6/SMURF1	0.016	0	-9999	-10000	0	0
BAMBI	-0.013	0.1	-9999	-0.69	1	1
SMURF2	0.016	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.12	0.27	-9999	-0.57	13	13
BMP2-4/GREM1	-0.052	0.18	-9999	-0.44	9	9
SMAD7	0.016	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	0.02	0.042	-9999	-10000	0	0
SMAD1/SMAD6	0.036	0.059	-9999	-10000	0	0
TAK1/SMAD6	0.023	0	-9999	-10000	0	0
BMP7	-0.036	0.076	-9999	-10000	0	0
BMP6	-0.082	0.24	-9999	-0.69	7	7
MAP3K7IP2	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	0.002	0.091	-9999	-10000	0	0
PPM1A	0.016	0	-9999	-10000	0	0
SMAD1/SMURF2	0.036	0.059	-9999	-10000	0	0
SMAD7/SMURF1	0.023	0	-9999	-10000	0	0
CTDSPL	-0.011	0.13	-9999	-0.69	2	2
PPP1CA	0.016	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0.016	0	-9999	-10000	0	0
PPP1R15A	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.06	0.17	-9999	-0.53	4	4
CHRD	0.016	0	-9999	-10000	0	0
BMPR2	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.012	0.11	-9999	-10000	0	0
BMP4	-0.046	0.19	-9999	-0.69	4	4
FST	-0.12	0.27	-9999	-0.69	10	10
BMP2-4/NOG	-0.068	0.17	-9999	-0.44	9	9
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.038	0.02	-9999	-10000	0	0

×

amb2 Integrin signaling

Figure S31. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S31. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.011	0.038	-9999	-10000	0	0
alphaM/beta2 Integrin/GPIbA	0.012	0.034	-9999	-10000	0	0
alphaM/beta2 Integrin/proMMP-9	-0.005	0.05	-9999	-10000	0	0
PLAUR	0	0.047	-9999	-10000	0	0
HMGB1	0.002	0.024	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	0.012	0.034	-9999	-10000	0	0
AGER	0.002	0.024	-9999	-10000	0	0
RAP1A	-0.024	0.16	-9999	-0.69	3	3
SELPLG	0.016	0	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.018	0.11	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.018	0.066	-9999	-10000	0	0
CYR61	-0.05	0.2	-9999	-0.69	5	5
TLN1	0.016	0	-9999	-10000	0	0
Rap1/GTP	-0.018	0.073	-9999	-0.31	3	3
RHOA	0.016	0	-9999	-10000	0	0
P-selectin oligomer	-0.45	0.33	-9999	-0.69	36	36
MYH2	0.043	0.064	-9999	-0.32	1	1
MST1R	0.016	0	-9999	-10000	0	0
leukocyte activation during inflammatory response	-0.006	0.012	-9999	-10000	0	0
APOB	0.016	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.013	0.022	-9999	-10000	0	0
JAM3	-0.18	0.32	-9999	-0.69	15	15
GP1BA	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/CTGF	0.004	0.076	-9999	-0.49	1	1
alphaM/beta2 Integrin	0.037	0.034	-9999	-10000	0	0
JAM3 homodimer	-0.18	0.32	-9999	-0.69	15	15
ICAM2	0.016	0	-9999	-10000	0	0
ICAM1	0.016	0	-9999	-10000	0	0
phagocytosis triggered by activation of immune response cell surface activating receptor	0.037	0.034	-9999	-10000	0	0
cell adhesion	0.012	0.034	-9999	-10000	0	0
NFKB1	-0.058	0.18	-9999	-10000	0	0
THY1	0.013	0.022	-9999	-10000	0	0
RhoA/GDP	0.012	0	-9999	-10000	0	0
Lipoprotein(a)	0.021	0	-9999	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	-0.12	0.2	-9999	-0.4	18	18
IL6	-0.21	0.41	-9999	-0.81	17	17
ITGB2	-0.001	0.03	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	0.011	0.04	-9999	-10000	0	0
alphaM/beta2 Integrin/JAM2/JAM3	-0.33	0.3	-9999	-0.53	35	35
JAM2	-0.39	0.35	-9999	-0.69	31	31
alphaM/beta2 Integrin/ICAM1	0.027	0.034	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA/Plg	0.017	0.033	-9999	-10000	0	0
RhoA/GTP	0.044	0.043	-9999	-10000	0	0
positive regulation of phagocytosis	-0.017	0.096	-9999	-0.57	1	1
Ron/MSP	0.017	0.024	-9999	-10000	0	0
alphaM/beta2 Integrin/uPAR/uPA	0.013	0.04	-9999	-10000	0	0
alphaM/beta2 Integrin/uPAR	0.004	0.044	-9999	-10000	0	0
PLAU	0.01	0.031	-9999	-10000	0	0
PLAT	-0.22	0.33	-9999	-0.69	18	18
actin filament polymerization	0.043	0.062	-9999	-0.3	1	1
MST1	0.006	0.037	-9999	-10000	0	0
alphaM/beta2 Integrin/lipoprotein(a)	0.021	0.029	-9999	-10000	0	0
TNF	-0.047	0.17	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	0.009	0.036	-9999	-10000	0	0
fibrinolysis	0.015	0.033	-9999	-10000	0	0
HCK	0.002	0.095	-9999	-0.69	1	1
dendritic cell antigen processing and presentation	0.037	0.034	-9999	-10000	0	0
VTN	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/CYR61	-0.03	0.15	-9999	-0.49	5	5
LPA	0.016	0	-9999	-10000	0	0
LRP1	0.016	0	-9999	-10000	0	0
cell migration	0.004	0.047	-9999	-10000	0	0
FN1	0.01	0.031	-9999	-10000	0	0
alphaM/beta2 Integrin/Thy1	0.01	0.036	-9999	-10000	0	0
MPO	0.013	0.022	-9999	-10000	0	0
KNG1	0.013	0.022	-9999	-10000	0	0
RAP1/GDP	-0.005	0.11	-9999	-0.44	3	3
ROCK1	0.05	0.042	-9999	-10000	0	0
ELA2	0.016	0	-9999	-10000	0	0
PLG	0.01	0.031	-9999	-10000	0	0
CTGF	0.002	0.095	-9999	-0.69	1	1
alphaM/beta2 Integrin/Hck	0.003	0.068	-9999	-0.43	1	1
ITGAM	0.002	0.024	-9999	-10000	0	0
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.26	0.21	-9999	-0.41	36	36
HP	-0.016	0.11	-9999	-0.69	1	1
leukocyte adhesion	-0.3	0.25	-9999	-0.57	20	20
SELP	-0.46	0.33	-9999	-0.69	36	36

×

Ceramide signaling pathway

Figure S32. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S32. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.034	0.17	-10000	0	-0.51	6	6
MAP4K4	0.009	0.11	-10000	0	-0.43	1	1
BAG4	0.016	0	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.016	0.071	0.16	5	-10000	0	5
NFKBIA	0.016	0	-10000	0	-10000	0	0
BIRC3	-0.043	0.19	-10000	0	-0.69	4	4
BAX	0.001	0.04	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
AKT1	0.024	0.012	-10000	0	-10000	0	0
BAD	-0.008	0.075	0.18	5	-10000	0	5
SMPD1	0.016	0.043	-10000	0	-0.21	1	1
RB1	-0.006	0.075	0.18	5	-10000	0	5
FADD/Caspase 8	0.022	0.099	-10000	0	-0.4	1	1
MAP2K4	-0.005	0.093	0.18	5	-0.46	1	6
NSMAF	0.016	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0	0.068	0.18	4	-10000	0	4
EGF	-0.17	0.31	-10000	0	-0.69	14	14
mol:ceramide	-0.016	0.08	0.19	5	-10000	0	5
MADD	0.016	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.054	0.19	-10000	0	-0.51	8	8
ASAH1	-0.011	0.13	-10000	0	-0.69	2	2
negative regulation of cell cycle	-0.007	0.074	0.18	5	-10000	0	5
cell proliferation	-0.11	0.15	-10000	0	-0.31	18	18
BID	0.011	0.074	-10000	0	-10000	0	0
MAP3K1	-0.013	0.098	0.18	5	-0.49	1	6
EIF2A	0.001	0.07	-10000	0	-10000	0	0
TRADD	0.016	0	-10000	0	-10000	0	0
CRADD	-0.037	0.18	-10000	0	-0.69	4	4
MAPK3	0.013	0.064	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.013	0.064	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.006	0.072	0.17	5	-10000	0	5
FADD	0.01	0.1	-10000	0	-0.43	1	1
KSR1	-0.006	0.075	0.18	5	-10000	0	5
MAPK8	-0.002	0.08	0.18	5	-0.31	1	6
PRKRA	-0.006	0.075	0.18	5	-10000	0	5
PDGFA	-0.063	0.22	-10000	0	-0.69	6	6
TRAF2	0.013	0.022	-10000	0	-10000	0	0
IGF1	-0.26	0.34	-10000	0	-0.69	21	21
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.016	0.08	0.19	5	-10000	0	5
CTSD	0.016	0	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.023	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.12	0.16	-10000	0	-0.33	18	18
PRKCD	0.016	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.054	0.19	-10000	0	-0.51	8	8
RelA/NF kappa B1	0.023	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.016	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.002	0.11	-10000	0	-0.46	1	1
TNFR1A/BAG4/TNF-alpha	0.018	0.065	-10000	0	-0.44	1	1
mol:Sphingosine-1-phosphate	-0.034	0.17	-10000	0	-0.51	6	6
MAP2K1	0.008	0.065	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
CYCS	0.047	0.09	0.17	15	-10000	0	15
TNFRSF1A	0.002	0.095	-10000	0	-0.69	1	1
NFKB1	0.016	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.013	0.072	-10000	0	-0.51	1	1
EIF2AK2	-0.007	0.073	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	0.018	0.065	-10000	0	-0.44	1	1
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.024	0.063	-10000	0	-10000	0	0
MAP2K2	0.008	0.065	-10000	0	-10000	0	0
SMPD3	0.017	0.05	-10000	0	-0.21	1	1
TNF	0.006	0.037	-10000	0	-10000	0	0
PKC zeta/PAR4	0.012	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.073	0.13	0.24	19	-10000	0	19
NF kappa B1/RelA/I kappa B alpha	0.037	0	-10000	0	-10000	0	0
AIFM1	0.046	0.089	0.17	14	-10000	0	14
BCL2	-0.19	0.32	-10000	0	-0.69	16	16

×

TCGA08_retinoblastoma

Figure S33. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S33. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.013	0.014	-10000	0	-10000	0	0
CDKN2C	-0.03	0.18	-10000	0	-0.66	4	4
CDKN2A	-0.045	0.078	-10000	0	-10000	0	0
CCND2	0.007	0.061	0.21	3	-0.14	3	6
RB1	-0.002	0.068	0.14	1	-0.21	4	5
CDK4	0.021	0.065	0.24	4	-10000	0	4
CDK6	0.008	0.076	0.22	4	-0.18	3	7
G1/S progression	0.002	0.068	0.21	4	-0.14	1	5

×

BCR signaling pathway

Figure S34. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S34. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.001	0.12	-10000	0	-0.34	4	4
IKBKB	0.034	0.063	-10000	0	-10000	0	0
AKT1	0.009	0.089	0.24	1	-0.24	3	4
IKBKG	0.036	0.064	-10000	0	-10000	0	0
CALM1	0.013	0.11	0.23	4	-0.29	4	8
PIK3CA	0.002	0.095	-10000	0	-0.69	1	1
MAP3K1	-0.03	0.17	-10000	0	-0.5	4	4
MAP3K7	0.015	0	-10000	0	-10000	0	0
mol:Ca2+	0.005	0.11	0.23	4	-0.32	4	8
DOK1	0.016	0	-10000	0	-10000	0	0
AP-1	-0.06	0.11	0.19	1	-0.19	3	4
LYN	0.012	0.022	-10000	0	-10000	0	0
BLNK	0.015	0	-10000	0	-10000	0	0
SHC1	0.016	0	-10000	0	-10000	0	0
BCR complex	-0.017	0.14	-10000	0	-0.51	4	4
CD22	-0.088	0.18	-10000	0	-0.49	8	8
CAMK2G	0.021	0.1	-10000	0	-0.29	1	1
CSNK2A1	0.016	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.022	0.084	-10000	0	-0.36	1	1
GO:0007205	0.005	0.11	0.23	4	-0.32	4	8
SYK	0.003	0.043	-10000	0	-10000	0	0
ELK1	0.013	0.11	0.23	4	-0.3	4	8
NFATC1	-0.029	0.18	-10000	0	-0.52	5	5
B-cell antigen/BCR complex	-0.017	0.14	-10000	0	-0.51	4	4
PAG1/CSK	0.009	0.074	-10000	0	-0.51	1	1
NFKBIB	0.026	0.027	-10000	0	-10000	0	0
HRAS	0.023	0.1	-10000	0	-0.29	4	4
NFKBIA	0.026	0.027	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.03	0.024	-10000	0	-10000	0	0
RasGAP/Csk	-0.11	0.21	-10000	0	-0.38	20	20
mol:GDP	0.01	0.11	0.23	4	-0.3	4	8
PTEN	0.002	0.095	-10000	0	-0.69	1	1
CD79B	-0.037	0.18	-10000	0	-0.69	4	4
NF-kappa-B/RelA/I kappa B alpha	0.03	0.024	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.008	0.16	-10000	0	-0.48	5	5
PIK3R1	0.002	0.095	-10000	0	-0.69	1	1
mol:IP3	0.004	0.12	0.23	4	-0.32	4	8
CSK	0.016	0	-10000	0	-10000	0	0
FOS	-0.15	0.2	-10000	0	-0.32	29	29
CHUK	0.036	0.064	-10000	0	-10000	0	0
IBTK	0.016	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.023	0.067	-10000	0	-10000	0	0
PTPN6	-0.053	0.18	-10000	0	-0.46	8	8
RELA	0.016	0	-10000	0	-10000	0	0
BCL2A1	0.027	0.018	-10000	0	-10000	0	0
VAV2	-0.044	0.18	-10000	0	-0.58	4	4
ubiquitin-dependent protein catabolic process	0.031	0.026	-10000	0	-10000	0	0
BTK	-0.013	0.13	-10000	0	-0.98	1	1
CD19	-0.087	0.18	-10000	0	-0.49	8	8
MAP4K1	0.016	0	-10000	0	-10000	0	0
CD72	0.016	0	-10000	0	-10000	0	0
PAG1	-0.004	0.099	-10000	0	-0.69	1	1
MAPK14	-0.016	0.15	-10000	0	-0.42	4	4
SH3BP5	-0.05	0.2	-10000	0	-0.69	5	5
PIK3AP1	0.01	0.12	0.26	3	-0.36	4	7
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.016	0.08	-10000	0	-10000	0	0
RAF1	0.029	0.099	-10000	0	-0.28	3	3
RasGAP/p62DOK/SHIP	-0.14	0.18	-10000	0	-0.36	20	20
CD79A	0.015	0	-10000	0	-10000	0	0
re-entry into mitotic cell cycle	-0.059	0.1	0.19	1	-0.19	3	4
RASA1	0.016	0	-10000	0	-10000	0	0
MAPK3	0.043	0.088	-10000	0	-10000	0	0
MAPK1	0.043	0.088	-10000	0	-10000	0	0
CD72/SHP1	-0.042	0.17	-10000	0	-0.53	4	4
NFKB1	0.016	0	-10000	0	-10000	0	0
MAPK8	-0.016	0.15	-10000	0	-0.42	4	4
actin cytoskeleton organization	-0.029	0.16	-10000	0	-0.49	4	4
NF-kappa-B/RelA	0.064	0.046	-10000	0	-10000	0	0
Calcineurin	-0.039	0.091	-10000	0	-0.3	3	3
PI3K	-0.058	0.14	-10000	0	-0.45	5	5
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.003	0.13	0.26	4	-0.38	4	8
SOS1	0.016	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.07	0.23	-10000	0	-0.65	6	6
DAPP1	-0.11	0.24	-10000	0	-0.73	6	6
cytokine secretion	-0.025	0.16	-10000	0	-0.48	5	5
mol:DAG	0.004	0.12	0.23	4	-0.32	4	8
PLCG2	-0.011	0.13	-10000	0	-0.69	2	2
MAP2K1	0.036	0.094	-10000	0	-0.27	1	1
B-cell antigen/BCR complex/FcgammaRIIB	-0.15	0.24	-10000	0	-0.46	20	20
mol:PI-3-4-5-P3	-0.038	0.11	0.32	1	-0.32	5	6
ETS1	0.028	0.097	-10000	0	-10000	0	0
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.013	0.11	-10000	0	-0.38	4	4
B-cell antigen/BCR complex/LYN	-0.094	0.19	-10000	0	-0.52	8	8
MALT1	0.012	0.022	-10000	0	-10000	0	0
TRAF6	0.015	0	-10000	0	-10000	0	0
RAC1	-0.032	0.17	-10000	0	-0.53	4	4
B-cell antigen/BCR complex/LYN/SYK	-0.075	0.16	-10000	0	-0.55	4	4
CARD11	0.01	0.11	0.23	4	-0.3	4	8
FCGR2B	-0.21	0.33	-10000	0	-0.69	17	17
PPP3CA	0.002	0.095	-10000	0	-0.69	1	1
BCL10	0.015	0	-10000	0	-10000	0	0
IKK complex	0.027	0.032	-10000	0	-10000	0	0
PTPRC	-0.037	0.18	-10000	0	-0.69	4	4
PDPK1	0.002	0.085	0.22	1	-0.25	2	3
PPP3CB	0.016	0	-10000	0	-10000	0	0
PPP3CC	-0.024	0.16	-10000	0	-0.69	3	3
POU2F2	0.028	0.017	-10000	0	-10000	0	0

×

Plasma membrane estrogen receptor signaling

Figure S35. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S35. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.016	0.13	-10000	0	-0.37	6	6
ER alpha/Gai/GDP/Gbeta gamma	-0.016	0.15	-10000	0	-0.39	7	7
AKT1	-0.062	0.27	-10000	0	-0.75	7	7
PIK3CA	0.002	0.095	-10000	0	-0.69	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.065	0.27	-10000	0	-0.76	7	7
mol:Ca2+	0	0.074	-10000	0	-0.39	1	1
IGF1R	0.016	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.056	0.18	-10000	0	-0.5	7	7
SHC1	0.016	0	-10000	0	-10000	0	0
apoptosis	0.058	0.26	0.72	7	-10000	0	7
RhoA/GTP	-0.038	0.1	-10000	0	-0.33	6	6
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.057	0.15	-10000	0	-0.44	7	7
regulation of stress fiber formation	-0.016	0.097	0.29	1	-10000	0	1
E2/ERA-ERB (dimer)	-0.04	0.14	-10000	0	-0.44	6	6
KRAS	0.016	0	-10000	0	-10000	0	0
G13/GTP	-0.036	0.13	-10000	0	-0.41	6	6
pseudopodium formation	0.016	0.097	-10000	0	-0.29	1	1
E2/ER alpha (dimer)/PELP1	-0.042	0.14	-10000	0	-0.44	6	6
GRB2	0.016	0	-10000	0	-10000	0	0
GNG2	0.016	0	-10000	0	-10000	0	0
GNAO1	0.016	0	-10000	0	-10000	0	0
HRAS	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.017	0.18	-10000	0	-0.48	7	7
E2/ER beta (dimer)	0.012	0	-10000	0	-10000	0	0
mol:GDP	-0.05	0.15	-10000	0	-0.46	6	6
mol:NADP	-0.017	0.18	-10000	0	-0.48	7	7
PIK3R1	0.002	0.095	-10000	0	-0.69	1	1
mol:IP3	-0.001	0.076	-10000	0	-0.41	1	1
IGF-1R heterotetramer	0.016	0	-10000	0	-10000	0	0
PLCB1	-0.009	0.078	-10000	0	-0.43	1	1
PLCB2	0.008	0.077	-10000	0	-0.43	1	1
IGF1	-0.26	0.34	-10000	0	-0.69	21	21
mol:L-citrulline	-0.017	0.18	-10000	0	-0.48	7	7
RHOA	0.016	0	-10000	0	-10000	0	0
Gai/GDP	0.012	0.11	-10000	0	-0.7	1	1
JNK cascade	0.012	0	-10000	0	-10000	0	0
BCAR1	0.016	0	-10000	0	-10000	0	0
ESR2	0.016	0	-10000	0	-10000	0	0
GNAQ	0	0	-10000	0	-10000	0	0
ESR1	-0.081	0.22	-10000	0	-0.69	6	6
Gq family/GDP/Gbeta gamma	0.032	0.041	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.006	0.1	-10000	0	-0.27	6	6
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.057	0.15	-10000	0	-0.44	7	7
GNAZ	0.016	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)	-0.059	0.17	-10000	0	-0.52	6	6
STRN	-0.011	0.13	-10000	0	-0.69	2	2
GNAL	0.016	0	-10000	0	-10000	0	0
PELP1	0.013	0.022	-10000	0	-10000	0	0
MAPK11	0.021	0	-10000	0	-10000	0	0
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.002	0.095	-10000	0	-0.69	1	1
GNAI1	-0.024	0.16	-10000	0	-0.69	3	3
HBEGF	-0.009	0.14	-10000	0	-0.35	7	7
cAMP biosynthetic process	-0.044	0.11	-10000	0	-0.36	6	6
SRC	-0.007	0.15	-10000	0	-0.37	7	7
PI3K	0.005	0.13	-10000	0	-0.94	1	1
GNB1	0.016	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.041	0.13	-10000	0	-0.4	6	6
SOS1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.14	0.19	-10000	0	-0.56	7	7
Gs family/GTP	-0.045	0.11	-10000	0	-0.36	6	6
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.029	0.011	-10000	0	-10000	0	0
vasodilation	-0.014	0.18	-10000	0	-0.46	7	7
mol:DAG	-0.001	0.076	-10000	0	-0.41	1	1
Gs family/GDP/Gbeta gamma	-0.039	0.12	-10000	0	-0.37	6	6
MSN	0.015	0.1	-10000	0	-0.31	1	1
Gq family/GTP	0	0.08	-10000	0	-0.46	1	1
mol:PI-3-4-5-P3	-0.061	0.26	-10000	0	-0.73	7	7
NRAS	0.013	0.022	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.014	0.18	0.46	7	-10000	0	7
GRB2/SOS1	0.023	0	-10000	0	-10000	0	0
RhoA/GDP	-0.045	0.14	-10000	0	-0.43	6	6
NOS3	-0.019	0.19	-10000	0	-0.5	7	7
GNA11	0.016	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.023	0.21	-10000	0	-0.55	7	7
E2/ER alpha (dimer)/PELP1/Src	-0.061	0.16	-10000	0	-0.46	7	7
ruffle organization	0.016	0.097	-10000	0	-0.29	1	1
ROCK2	0.007	0.11	-10000	0	-0.3	6	6
GNA14	0.002	0.095	-10000	0	-0.69	1	1
GNA15	0.016	0	-10000	0	-10000	0	0
GNA13	0.016	0	-10000	0	-10000	0	0
MMP9	-0.011	0.14	-10000	0	-0.35	7	7
MMP2	0	0.14	-10000	0	-0.34	7	7

×

Caspase cascade in apoptosis

Figure S36. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S36. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.041	0.085	0.22	3	-0.32	2	5
ACTA1	0.019	0.13	0.26	3	-0.5	2	5
NUMA1	0.041	0.085	-10000	0	-0.32	2	2
SPTAN1	0.038	0.11	0.25	3	-0.42	2	5
LIMK1	0.038	0.11	0.25	3	-0.42	2	5
BIRC3	-0.043	0.19	-10000	0	-0.69	4	4
BIRC2	0.016	0	-10000	0	-10000	0	0
BAX	0.006	0.037	-10000	0	-10000	0	0
CASP10	0.012	0.089	-10000	0	-0.44	2	2
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.041	0.085	-10000	0	-0.32	2	2
DIABLO	0.016	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.038	0.1	0.25	3	-0.41	2	5
response to UV	0	0	-10000	0	-10000	0	0
CRADD	-0.037	0.18	-10000	0	-0.69	4	4
GSN	-0.006	0.18	0.26	3	-0.43	7	10
MADD	0.016	0	-10000	0	-10000	0	0
TFAP2A	0.031	0.017	-10000	0	-10000	0	0
BID	0.016	0.049	-10000	0	-0.23	2	2
MAP3K1	0.017	0.084	-10000	0	-0.5	1	1
TRADD	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.023	0.001	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.002	0.18	0.25	2	-0.56	4	6
CASP9	0.016	0.001	-10000	0	-10000	0	0
DNA repair	-0.03	0.06	-10000	0	-0.22	4	4
neuron apoptosis	0.031	0.014	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.045	0.1	-10000	0	-0.39	2	2
APAF1	0.016	0	-10000	0	-10000	0	0
CASP6	0.041	0.05	-10000	0	-10000	0	0
TRAF2	0.013	0.022	-10000	0	-10000	0	0
ICAD/CAD	0.044	0.1	-10000	0	-0.4	2	2
CASP7	0.025	0.082	0.31	4	-10000	0	4
KRT18	0.023	0.016	-10000	0	-10000	0	0
apoptosis	0.034	0.13	0.28	3	-0.47	2	5
DFFA	0.038	0.11	0.25	3	-0.42	2	5
DFFB	0.038	0.11	0.25	3	-0.42	2	5
PARP1	0.03	0.061	0.22	4	-10000	0	4
actin filament polymerization	-0.037	0.11	0.36	3	-10000	0	3
TNF	0.006	0.037	-10000	0	-10000	0	0
CYCS	0.017	0.041	-10000	0	-0.16	1	1
SATB1	-0.03	0.15	-10000	0	-10000	0	0
SLK	0.038	0.11	0.25	3	-0.42	2	5
p15 BID/BAX	0.019	0.046	-10000	0	-0.2	2	2
CASP2	0.016	0.095	-10000	0	-0.4	1	1
JNK cascade	-0.017	0.084	0.5	1	-10000	0	1
CASP3	0.032	0.11	0.27	3	-0.44	2	5
LMNB2	0.033	0.056	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
CASP4	0.002	0.095	-10000	0	-0.69	1	1
Mammalian IAPs/DIABLO	-0.005	0.11	-10000	0	-0.4	4	4
negative regulation of DNA binding	0.031	0.017	-10000	0	-10000	0	0
stress fiber formation	0.038	0.1	0.25	3	-0.41	2	5
GZMB	0.002	0.1	-10000	0	-0.51	2	2
CASP1	-0.11	0.22	-10000	0	-0.42	16	16
LMNB1	0.032	0.056	-10000	0	-10000	0	0
APP	0.031	0.014	-10000	0	-10000	0	0
TNFRSF1A	0.002	0.095	-10000	0	-0.69	1	1
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.013	0	-10000	0	-10000	0	0
VIM	0.028	0.13	0.28	3	-0.48	2	5
LMNA	0.035	0.056	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.008	0.1	-10000	0	-0.42	1	1
LRDD	0.016	0	-10000	0	-10000	0	0
SREBF1	0.036	0.1	0.25	2	-0.42	2	4
APAF-1/Caspase 9	0.011	0.041	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.041	0.084	-10000	0	-0.32	2	2
CFL2	0.037	0.11	-10000	0	-0.37	3	3
GAS2	0	0.15	0.25	3	-0.38	6	9
positive regulation of apoptosis	0.035	0.059	-10000	0	-10000	0	0
PRF1	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

Figure S37. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S37. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.04	0	-9999	-10000	0	0
HDAC3	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.004	-9999	-10000	0	0
GATA1/HDAC4	0.021	0.014	-9999	-10000	0	0
GATA1/HDAC5	0.023	0	-9999	-10000	0	0
GATA2/HDAC5	0.006	0.039	-9999	-10000	0	0
HDAC5/BCL6/BCoR	0.023	0.063	-9999	-0.44	1	1
HDAC9	0.016	0	-9999	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	-0.3	0.21	-9999	-0.44	39	39
HDAC4/ANKRA2	0.021	0.014	-9999	-10000	0	0
HDAC5/YWHAB	0.023	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.025	0	-9999	-10000	0	0
GATA2	-0.012	0.061	-9999	-10000	0	0
HDAC4/RFXANK	0.013	0.03	-9999	-10000	0	0
BCOR	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.016	0	-9999	-10000	0	0
HDAC5	0.016	0	-9999	-10000	0	0
GNB1/GNG2	0.023	0	-9999	-10000	0	0
Histones	0.038	0.006	-9999	-10000	0	0
ADRBK1	0.016	0	-9999	-10000	0	0
HDAC4	0.013	0.022	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
HDAC5/ANKRA2	0.023	0	-9999	-10000	0	0
HDAC4/Ubc9	0.021	0.014	-9999	-10000	0	0
HDAC7	0	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0.023	0	-9999	-10000	0	0
TUBA1B	0.016	0	-9999	-10000	0	0
HDAC6	0.016	0	-9999	-10000	0	0
HDAC5/RFXANK	0.015	0.027	-9999	-10000	0	0
CAMK4	0.01	0.031	-9999	-10000	0	0
Tubulin/HDAC6	-0.12	0.22	-9999	-0.44	18	18
SUMO1	0.016	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
GATA1	0.016	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
NR3C1	-0.49	0.32	-9999	-0.69	39	39
SUMO1/HDAC4	0.034	0.009	-9999	-10000	0	0
SRF	0.016	0	-9999	-10000	0	0
HDAC4/YWHAB	0.021	0.014	-9999	-10000	0	0
Tubulin	-0.16	0.25	-9999	-0.51	18	18
HDAC4/14-3-3 E	0.021	0.014	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
RANGAP1	0.016	0	-9999	-10000	0	0
BCL6/BCoR	0.013	0.072	-9999	-0.51	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0.03	0.012	-9999	-10000	0	0
HDAC4/SRF	0.027	0.02	-9999	-10000	0	0
HDAC4/ER alpha	-0.05	0.17	-9999	-0.51	6	6
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.037	0.006	-9999	-10000	0	0
cell motility	-0.12	0.22	-9999	-0.43	18	18
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
HDAC7/HDAC3	0.012	0	-9999	-10000	0	0
BCL6	0.002	0.095	-9999	-0.69	1	1
HDAC4/CaMK II delta B	0.013	0.022	-9999	-10000	0	0
Hsp90/HDAC6	0.023	0	-9999	-10000	0	0
ESR1	-0.081	0.22	-9999	-0.69	6	6
HDAC6/HDAC11	0.021	0.014	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.038	0	-9999	-10000	0	0
NPC	0.009	0	-9999	-10000	0	0
MEF2C	-0.17	0.31	-9999	-0.69	14	14
RAN	0.016	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.06	0.18	-9999	-0.36	14	14
GNG2	0.016	0	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
TUBB2A	-0.22	0.33	-9999	-0.69	18	18
HDAC11	0.013	0.022	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
RANBP2	0.016	0	-9999	-10000	0	0
ANKRA2	0.016	0	-9999	-10000	0	0
RFXANK	0.003	0.043	-9999	-10000	0	0
nuclear import	-0.033	0.008	-9999	-10000	0	0

×

ErbB4 signaling events

Figure S38. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S38. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.009	0.12	-9999	-0.4	3	3
epithelial cell differentiation	-0.022	0.066	-9999	-10000	0	0
ITCH	0.022	0.016	-9999	-10000	0	0
WWP1	0.017	0.061	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
EGFR	-0.066	0.22	-9999	-0.69	6	6
PRL	0.016	0	-9999	-10000	0	0
neuron projection morphogenesis	0.058	0.042	-9999	-10000	0	0
PTPRZ1	-0.089	0.25	-9999	-0.69	8	8
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.045	0.044	-9999	-10000	0	0
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.023	0.051	-9999	-10000	0	0
ADAM17	0.019	0.028	-9999	-10000	0	0
ErbB4/ErbB4	0.011	0.078	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.014	0.066	-9999	-10000	0	0
NCOR1	0.016	0	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.03	0.048	-9999	-10000	0	0
GRIN2B	0.03	0.068	-9999	-0.34	1	1
ErbB4/ErbB2/betacellulin	0.02	0.084	-9999	-0.48	1	1
STAT1	0.006	0.037	-9999	-10000	0	0
HBEGF	-0.024	0.16	-9999	-0.69	3	3
PRLR	0.016	0	-9999	-10000	0	0
E4ICDs/ETO2	-0.24	0.23	-9999	-0.43	31	31
axon guidance	0.041	0.088	-9999	-0.29	1	1
NEDD4	-0.074	0.24	-9999	-0.69	7	7
Prolactin receptor/Prolactin receptor/Prolactin	0.023	0	-9999	-10000	0	0
CBFA2T3	-0.39	0.35	-9999	-0.69	31	31
ErbB4/ErbB2/HBEGF	0.005	0.1	-9999	-0.36	3	3
MAPK3	0.051	0.043	-9999	-10000	0	0
STAT1 (dimer)	0.011	0.07	-9999	-10000	0	0
MAPK1	0.051	0.043	-9999	-10000	0	0
JAK2	0.016	0	-9999	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	0.027	0.051	-9999	-10000	0	0
NRG1	0.028	0.017	-9999	-10000	0	0
NRG3	0.013	0.022	-9999	-10000	0	0
NRG2	-0.14	0.29	-9999	-0.69	12	12
NRG4	0.01	0.031	-9999	-10000	0	0
heart development	0.041	0.088	-9999	-0.29	1	1
neural crest cell migration	0.027	0.051	-9999	-10000	0	0
ERBB2	0.024	0.026	-9999	-10000	0	0
WWOX/E4ICDs	0.016	0.065	-9999	-10000	0	0
SHC1	0.016	0	-9999	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.022	0.16	-9999	-0.44	6	6
apoptosis	0.015	0.043	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.082	0.2	-9999	-0.43	12	12
ErbB4/ErbB2/epiregulin	0.027	0.052	-9999	-10000	0	0
ErbB4/ErbB4/betacellulin/betacellulin	0.008	0.1	-9999	-0.56	1	1
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.018	0.099	-9999	-10000	0	0
MDM2	0.018	0.071	-9999	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.028	0.036	-9999	-10000	0	0
STAT5A	0.046	0.081	-9999	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.015	0.15	-9999	-0.42	6	6
DLG4	0.016	0	-9999	-10000	0	0
GRB2/SHC	0.023	0	-9999	-10000	0	0
E4ICDs/TAB2/NCoR1	0.024	0.06	-9999	-10000	0	0
STAT5A (dimer)	-0.023	0.07	-9999	-10000	0	0
MAP3K7IP2	0.016	0	-9999	-10000	0	0
STAT5B (dimer)	0.044	0.078	-9999	-10000	0	0
LRIG1	-0.017	0.14	-9999	-0.69	2	2
EREG	0.013	0.022	-9999	-10000	0	0
BTC	0.002	0.095	-9999	-0.69	1	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.041	0.088	-9999	-0.29	1	1
ERBB4	0.011	0.078	-9999	-10000	0	0
STAT5B	0.016	0	-9999	-10000	0	0
YAP1	-0.006	0.015	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.027	0.051	-9999	-10000	0	0
glial cell differentiation	-0.024	0.06	-9999	-10000	0	0
WWOX	0.016	0	-9999	-10000	0	0
cell proliferation	0.035	0.082	-9999	-0.35	1	1

×

Sphingosine 1-phosphate (S1P) pathway

Figure S39. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S39. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.016	0	-9999	-10000	0	0
SPHK1	0.002	0.095	-9999	-0.69	1	1
GNAI2	0.016	0	-9999	-10000	0	0
mol:S1P	0.012	0.048	-9999	-0.32	1	1
GNAO1	0.016	0	-9999	-10000	0	0
mol:Sphinganine-1-P	0.016	0.073	-9999	-0.51	1	1
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.027	0.035	-9999	-10000	0	0
GNAI3	0.002	0.095	-9999	-0.69	1	1
G12/G13	0.023	0	-9999	-10000	0	0
S1PR3	0	0	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	-0.39	0.35	-9999	-0.69	31	31
S1P1/S1P	-0.24	0.23	-9999	-0.43	31	31
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
GNAI1	-0.024	0.16	-9999	-0.69	3	3
S1P/S1P5/G12	0.017	0.038	-9999	-0.24	1	1
S1P/S1P3/Gq	0.021	0.045	-9999	-0.26	1	1
S1P/S1P4/Gi	0.016	0.098	-9999	-0.34	3	3
GNAQ	0	0	-9999	-10000	0	0
GNAZ	0.016	0	-9999	-10000	0	0
GNA14	0.002	0.095	-9999	-0.69	1	1
GNA15	0.016	0	-9999	-10000	0	0
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.016	0	-9999	-10000	0	0
ABCC1	-0.009	0.058	-9999	-10000	0	0

×

Signaling events mediated by PTP1B

Figure S40. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S40. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-10000	0	-10000	0	0
Jak2/Leptin Receptor	-0.083	0.17	-10000	0	-0.37	13	13
PTP1B/AKT1	-0.013	0.065	-10000	0	-0.26	1	1
FYN	0.016	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.025	0.072	-10000	0	-0.25	2	2
EGFR	-0.07	0.22	-10000	0	-0.7	6	6
EGF/EGFR	-0.14	0.23	-10000	0	-0.46	17	17
CSF1	0.016	0	-10000	0	-10000	0	0
AKT1	0.016	0	-10000	0	-10000	0	0
INSR	0.016	0	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.051	0.076	-10000	0	-0.26	2	2
Insulin Receptor/Insulin	-0.017	0.036	-10000	0	-10000	0	0
HCK	0.002	0.095	-10000	0	-0.69	1	1
CRK	0.016	0	-10000	0	-10000	0	0
TYK2	-0.015	0.069	-10000	0	-0.28	1	1
EGF	-0.17	0.31	-10000	0	-0.7	14	14
YES1	0.016	0	-10000	0	-10000	0	0
CAV1	-0.19	0.14	-10000	0	-0.39	14	14
TXN	0.009	0.006	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.047	0.14	-10000	0	-0.4	6	6
cell migration	0.025	0.072	0.25	2	-10000	0	2
STAT3	0.014	0.001	-10000	0	-10000	0	0
PRLR	0.02	0.001	-10000	0	-10000	0	0
ITGA2B	0.011	0.022	-10000	0	-10000	0	0
CSF1R	0.016	0	-10000	0	-10000	0	0
Prolactin Receptor/Prolactin	0.033	0.002	-10000	0	-10000	0	0
FGR	0.016	0	-10000	0	-10000	0	0
PTP1B/p130 Cas	-0.015	0.069	-10000	0	-0.28	1	1
Crk/p130 Cas	-0.005	0.068	-10000	0	-0.27	1	1
DOK1	-0.002	0.061	-10000	0	-0.24	1	1
JAK2	0.001	0.043	-10000	0	-10000	0	0
Jak2/Leptin Receptor/Leptin	-0.23	0.15	-10000	0	-0.41	13	13
PIK3R1	0.002	0.095	-10000	0	-0.69	1	1
PTPN1	-0.025	0.073	-10000	0	-0.25	2	2
LYN	0.013	0.022	-10000	0	-10000	0	0
CDH2	-0.075	0.081	-10000	0	-10000	0	0
SRC	0.008	0.029	-10000	0	-10000	0	0
ITGB3	0.005	0.037	-10000	0	-10000	0	0
CAT1/PTP1B	0.014	0.073	-10000	0	-0.25	1	1
CAPN1	0.013	0.001	-10000	0	-10000	0	0
CSK	0.016	0	-10000	0	-10000	0	0
PI3K	-0.022	0.096	-10000	0	-0.69	1	1
mol:H2O2	-0.004	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.2	0.13	-10000	0	-0.38	9	9
negative regulation of transcription	0.001	0.043	-10000	0	-10000	0	0
FCGR2A	0.016	0	-10000	0	-10000	0	0
FER	0.009	0.006	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.002	0.031	-10000	0	-10000	0	0
BLK	0.013	0.022	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.032	0.001	-10000	0	-10000	0	0
RHOA	0.013	0.001	-10000	0	-10000	0	0
LEPR	-0.15	0.3	-10000	0	-0.69	13	13
BCAR1	0.016	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.016	0	-10000	0	-10000	0	0
mol:NADPH	-0.004	0.004	-10000	0	-10000	0	0
TRPV6	0.043	0.036	-10000	0	-10000	0	0
PRL	0.02	0.001	-10000	0	-10000	0	0
SOCS3	0.023	0.024	-10000	0	-10000	0	0
SPRY2	-0.042	0.18	-10000	0	-0.7	4	4
Insulin Receptor/Insulin/IRS1	-0.021	0.15	-10000	0	-0.44	6	6
CSF1/CSF1R	-0.005	0.068	-10000	0	-0.27	1	1
Ras protein signal transduction	0.025	0.022	-10000	0	-10000	0	0
IRS1	-0.063	0.22	-10000	0	-0.69	6	6
INS	0.016	0	-10000	0	-10000	0	0
LEP	-0.44	0.34	-10000	0	-0.69	35	35
STAT5B	-0.011	0.06	-10000	0	-0.24	1	1
STAT5A	-0.011	0.06	-10000	0	-0.24	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.015	0.069	-10000	0	-0.28	1	1
CSN2	0.038	0.016	-10000	0	-10000	0	0
PIK3CA	0.002	0.095	-10000	0	-0.69	1	1
LAT	0.008	0.029	-10000	0	-10000	0	0
YBX1	0.022	0.002	-10000	0	-10000	0	0
LCK	0.01	0.031	-10000	0	-10000	0	0
SHC1	0.016	0	-10000	0	-10000	0	0
NOX4	0.012	0.004	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

Figure S41. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S41. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.034	0.009	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
Rac1/GDP	0.012	0	-9999	-10000	0	0
DOCK1	0.016	0	-9999	-10000	0	0
ITGA4	0.013	0.022	-9999	-10000	0	0
alpha4/beta7 Integrin/MAdCAM1	0.039	0.011	-9999	-10000	0	0
EPO	0.016	0	-9999	-10000	0	0
alpha4/beta7 Integrin	0.021	0.014	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.021	0.014	-9999	-10000	0	0
EPO/EPOR (dimer)	0.017	0.024	-9999	-10000	0	0
lamellipodium assembly	-0.006	0.078	-9999	-0.57	1	1
PIK3CA	0.002	0.095	-9999	-0.69	1	1
PI3K	0.005	0.13	-9999	-0.94	1	1
ARF6	0.016	0	-9999	-10000	0	0
JAK2	0.035	0.013	-9999	-10000	0	0
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.002	0.095	-9999	-0.69	1	1
MADCAM1	0.016	0	-9999	-10000	0	0
cell adhesion	0.037	0.011	-9999	-10000	0	0
CRKL/CBL	0.023	0	-9999	-10000	0	0
ITGB1	0.016	0	-9999	-10000	0	0
SRC	-0.082	0.19	-9999	-0.39	15	15
ITGB7	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.1	0.21	-9999	-0.44	15	15
p130Cas/Crk/Dock1	-0.046	0.17	-9999	-0.31	15	15
VCAM1	-0.18	0.32	-9999	-0.69	15	15
RHOA	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.039	0.011	-9999	-10000	0	0
BCAR1	-0.069	0.18	-9999	-0.36	15	15
EPOR	0.006	0.037	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
Rac1/GTP	-0.007	0.081	-9999	-0.59	1	1

×

TRAIL signaling pathway

Figure S42. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S42. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.063	0.22	-9999	-0.69	6	6
positive regulation of NF-kappaB transcription factor activity	-0.04	0.17	-9999	-0.51	6	6
MAP2K4	0.016	0.1	-9999	-0.38	1	1
IKBKB	0.016	0	-9999	-10000	0	0
TNFRSF10B	0.01	0.031	-9999	-10000	0	0
TNFRSF10A	0.016	0	-9999	-10000	0	0
SMPD1	-0.009	0.086	-9999	-0.25	6	6
IKBKG	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.01	0.031	-9999	-10000	0	0
TRAIL/TRAILR2	-0.04	0.17	-9999	-0.53	6	6
TRAIL/TRAILR3	-0.036	0.17	-9999	-0.51	6	6
TRAIL/TRAILR1	-0.036	0.17	-9999	-0.51	6	6
TRAIL/TRAILR4	-0.04	0.17	-9999	-0.51	6	6
TRAIL/TRAILR1/DAP3/GTP	-0.018	0.14	-9999	-0.4	6	6
IKK complex	-0.016	0.048	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0.012	0	-9999	-10000	0	0
MAPK3	-0.034	0.17	-9999	-0.51	6	6
MAP3K1	0.008	0.11	-9999	-0.35	2	2
TRAILR4 (trimer)	0.009	0.031	-9999	-10000	0	0
TRADD	0.016	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.007	0.1	-9999	-10000	0	0
CFLAR	0.002	0.095	-9999	-0.69	1	1
MAPK1	-0.034	0.17	-9999	-0.51	6	6
TRAIL/TRAILR1/FADD/TRADD/RIP	0.001	0.13	-9999	-0.36	6	6
mol:ceramide	-0.009	0.086	-9999	-0.25	6	6
FADD	0.016	0	-9999	-10000	0	0
MAPK8	0.023	0.1	-9999	-0.36	1	1
TRAF2	0.013	0.022	-9999	-10000	0	0
TRAILR3 (trimer)	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	-0.02	0.15	-9999	-0.44	6	6
DAP3	0.016	0	-9999	-10000	0	0
CASP10	-0.045	0.14	-9999	-0.42	6	6
JNK cascade	-0.04	0.17	-9999	-0.51	6	6
TRAIL (trimer)	-0.063	0.22	-9999	-0.69	6	6
TNFRSF10C	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.008	0.13	-9999	-0.37	6	6
TRAIL/TRAILR2/FADD	-0.023	0.15	-9999	-0.45	6	6
cell death	-0.009	0.085	-9999	-0.25	6	6
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.005	0.1	-9999	-0.31	1	1
TRAILR2 (trimer)	0.009	0.031	-9999	-10000	0	0
CASP8	0.012	0.055	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0	0.13	-9999	-0.37	6	6

×

IL1-mediated signaling events

Figure S43. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S43. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.012	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
MAP3K7IP2	0.016	0	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.07	0.12	-9999	-0.37	4	4
IRAK/TOLLIP	0.029	0	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
IKBKG	0.016	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.014	0.054	-9999	-10000	0	0
IL1A	-0.003	0.051	-9999	-10000	0	0
IL1B	-0.15	0.28	-9999	-0.57	16	16
IRAK/TRAF6/p62/Atypical PKCs	0.04	0.002	-9999	-10000	0	0
IL1R2	-0.024	0.07	-9999	-10000	0	0
IL1R1	-0.024	0.16	-9999	-0.69	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.038	0.14	-9999	-0.44	4	4
TOLLIP	0.016	0	-9999	-10000	0	0
TICAM2	0	0	-9999	-10000	0	0
MAP3K3	0.016	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0.032	0	-9999	-10000	0	0
IKK complex/ELKS	0.073	0.003	-9999	-10000	0	0
JUN	0.045	0.051	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.11	0.3	-9999	-0.49	16	16
IL1 alpha/IL1R1/IL1RAP/MYD88	0.005	0.11	-9999	-0.41	3	3
PIK3R1	0.002	0.095	-9999	-0.69	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.016	0.1	-9999	-0.38	3	3
IL1 beta fragment/IL1R1/IL1RAP	-0.13	0.28	-9999	-0.51	16	16
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	0.045	0.023	-9999	-10000	0	0
IRAK1	0.021	0	-9999	-10000	0	0
IL1RN/IL1R1	-0.012	0.12	-9999	-0.51	3	3
IRAK4	0.016	0	-9999	-10000	0	0
PRKCI	0.013	0.022	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
PI3K	0.005	0.13	-9999	-0.94	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.051	0.17	-9999	-0.5	4	4
CHUK	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.13	0.28	-9999	-0.51	16	16
IL1 beta/IL1R2	-0.14	0.24	-9999	-0.49	16	16
IRAK/TRAF6/TAK1/TAB1/TAB2	0.049	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.13	0.24	-9999	-0.71	5	5
IRAK3	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.11	0.26	-9999	-0.46	16	16
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.019	0.077	-9999	-0.29	3	3
IL1 alpha/IL1R1/IL1RAP	-0.007	0.12	-9999	-0.46	3	3
RELA	0.016	0	-9999	-10000	0	0
MAP3K7IP1	0.016	0	-9999	-10000	0	0
SQSTM1	0.016	0	-9999	-10000	0	0
MYD88	0.016	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.038	0	-9999	-10000	0	0
IL1RAP	0.01	0.031	-9999	-10000	0	0
UBE2N	0.016	0	-9999	-10000	0	0
IRAK/TRAF6	-0.11	0.2	-9999	-0.59	5	5
CASP1	-0.19	0.32	-9999	-0.69	16	16
IL1RN/IL1R2	-0.008	0.048	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.11	0.27	-9999	-0.48	16	16
TMEM189-UBE2V1	0	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.022	0.088	-9999	-0.34	3	3
PIK3CA	0.002	0.095	-9999	-0.69	1	1
IL1RN	0.006	0.037	-9999	-10000	0	0
TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
MAP2K6	0.046	0.006	-9999	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

Figure S44. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S44. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.003	0.019	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.15	0.13	-9999	-0.43	6	6
JUN	0.029	0.082	-9999	-0.33	1	1
HRAS	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.006	0.12	-9999	-0.39	5	5
RAP1A	-0.024	0.16	-9999	-0.69	3	3
FRS2	0.016	0	-9999	-10000	0	0
RAP1A/GDP	-0.018	0.12	-9999	-0.52	3	3
RET51/GFRalpha1/GDNF/DOK1	0.018	0.083	-9999	-0.39	2	2
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	0.013	0.081	-9999	-0.4	2	2
RHOA	0.016	0	-9999	-10000	0	0
RAP1A/GTP	-0.03	0.1	-9999	-0.35	5	5
GRB7	0.01	0.031	-9999	-10000	0	0
RET51/GFRalpha1/GDNF	0.018	0.083	-9999	-0.39	2	2
MAPKKK cascade	-0.012	0.062	-9999	-10000	0	0
BCAR1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.035	0.15	-9999	-0.4	8	8
lamellipodium assembly	-0.15	0.12	-9999	-0.39	7	7
RET51/GFRalpha1/GDNF/SHC	0.018	0.083	-9999	-0.39	2	2
PIK3CA	0.002	0.095	-9999	-0.69	1	1
RET9/GFRalpha1/GDNF/SHC	0.013	0.081	-9999	-0.4	2	2
RET9/GFRalpha1/GDNF/Shank3	0.013	0.081	-9999	-0.4	2	2
MAPK3	0.009	0.11	-9999	-0.32	5	5
DOK1	0.016	0	-9999	-10000	0	0
DOK6	-0.003	0.051	-9999	-10000	0	0
PXN	0.016	0	-9999	-10000	0	0
neurite development	0.022	0.1	-9999	-10000	0	0
DOK5	-0.011	0.13	-9999	-0.69	2	2
GFRA1	-0.014	0.13	-9999	-0.69	2	2
MAPK8	0.03	0.069	-9999	-10000	0	0
HRAS/GTP	-0.014	0.071	-9999	-0.36	2	2
tube development	0.02	0.077	-9999	-0.37	2	2
MAPK1	0.009	0.11	-9999	-0.32	5	5
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.023	0.06	-9999	-0.28	2	2
Rac1/GDP	0.012	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PDLIM7	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	0.026	0.085	-9999	-0.39	2	2
SHC1	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	0.018	0.083	-9999	-0.39	2	2
RET51/GFRalpha1/GDNF/Dok5	0.002	0.11	-9999	-0.39	4	4
PRKCA	0.016	0	-9999	-10000	0	0
HRAS/GDP	0.012	0	-9999	-10000	0	0
CREB1	0.03	0.066	-9999	-0.31	2	2
PIK3R1	0.002	0.095	-9999	-0.69	1	1
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.017	0.073	-9999	-0.28	3	3
RET51/GFRalpha1/GDNF/Grb7	0.015	0.083	-9999	-0.39	2	2
mol:GDP	0	0	-9999	-10000	0	0
RET	0.006	0.037	-9999	-10000	0	0
DOK4	0.016	0	-9999	-10000	0	0
JNK cascade	0.029	0.081	-9999	-0.32	1	1
RET9/GFRalpha1/GDNF/FRS2	0.013	0.081	-9999	-0.4	2	2
SHANK3	0.016	0	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
NCK1	0.002	0.095	-9999	-0.69	1	1
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.023	0.061	-9999	-0.28	2	2
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.028	0.06	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	0.022	0.073	-9999	-0.28	3	3
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.028	0.06	-9999	-0.28	2	2
PI3K	-0.2	0.22	-9999	-0.63	7	7
SOS1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.021	0.077	-9999	-0.37	2	2
GRB10	-0.024	0.16	-9999	-0.69	3	3
activation of MAPKK activity	0.029	0.058	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/FRS2	0.018	0.083	-9999	-0.39	2	2
GAB1	0.002	0.095	-9999	-0.69	1	1
IRS1	-0.063	0.22	-9999	-0.69	6	6
IRS2	-0.43	0.34	-9999	-0.69	34	34
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.022	0.073	-9999	-0.28	3	3
RET51/GFRalpha1/GDNF/PKC alpha	0.018	0.083	-9999	-0.39	2	2
GRB2	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GDNF	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.029	0.16	-9999	-0.4	8	8
Rac1/GTP	-0.17	0.15	-9999	-0.5	6	6
RET9/GFRalpha1/GDNF	0.002	0.088	-9999	-0.44	2	2
GFRalpha1/GDNF	0.001	0.1	-9999	-0.51	2	2

×

FoxO family signaling

Figure S45. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S45. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.051	0.012	-9999	-10000	0	0
PLK1	-0.13	0.26	-9999	-0.76	3	3
CDKN1B	-0.047	0.19	-9999	-0.42	7	7
FOXO3	-0.15	0.28	-9999	-0.5	13	13
KAT2B	-0.016	0.028	-9999	-0.043	27	27
FOXO1/SIRT1	0.038	0.027	-9999	-10000	0	0
CAT	-0.16	0.37	-9999	-1.4	3	3
CTNNB1	0.016	0	-9999	-10000	0	0
AKT1	0.008	0.025	-9999	-10000	0	0
FOXO1	0.046	0.014	-9999	-10000	0	0
MAPK10	0.033	0.016	-9999	-10000	0	0
mol:GTP	0.002	0.002	-9999	-10000	0	0
FOXO4	0.081	0.076	-9999	-0.33	1	1
response to oxidative stress	-0.01	0.029	-9999	-0.042	14	14
FOXO3A/SIRT1	-0.19	0.23	-9999	-0.48	13	13
XPO1	0.016	0.001	-9999	-10000	0	0
EP300	0.018	0.001	-9999	-10000	0	0
BCL2L11	0.008	0.038	-9999	-10000	0	0
FOXO1/SKP2	0.048	0.011	-9999	-10000	0	0
mol:GDP	-0.01	0.029	-9999	-0.042	14	14
RAN	0.017	0.001	-9999	-10000	0	0
GADD45A	-0.026	0.23	-9999	-1	2	2
YWHAQ	0.016	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.082	0.009	-9999	-10000	0	0
MST1	-0.006	0.044	-9999	-0.19	1	1
CSNK1D	0.013	0.022	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.06	0.012	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
MAPK8	0.034	0.016	-9999	-10000	0	0
MAPK9	0.026	0.063	-9999	-0.42	1	1
YWHAG	0.016	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
YWHAZ	0.016	0	-9999	-10000	0	0
SIRT1	0.014	0.007	-9999	-10000	0	0
SOD2	-0.009	0.17	-9999	-0.47	2	2
RBL2	-0.057	0.2	-9999	-0.54	3	3
RAL/GDP	0.018	0.021	-9999	-10000	0	0
CHUK	0.004	0.024	-9999	-10000	0	0
Ran/GTP	0.015	0.004	-9999	-10000	0	0
CSNK1G2	0.016	0	-9999	-10000	0	0
RAL/GTP	0.027	0.021	-9999	-10000	0	0
CSNK1G1	0.016	0	-9999	-10000	0	0
FASLG	0.008	0.038	-9999	-10000	0	0
SKP2	0.016	0	-9999	-10000	0	0
USP7	0.017	0.001	-9999	-10000	0	0
IKBKB	0.004	0.024	-9999	-10000	0	0
CCNB1	-0.14	0.27	-9999	-0.79	3	3
FOXO1-3a-4/beta catenin	0.011	0.17	-9999	-0.38	3	3
proteasomal ubiquitin-dependent protein catabolic process	0.048	0.011	-9999	-10000	0	0
CSNK1A1	0.016	0	-9999	-10000	0	0
SGK1	-0.016	0.028	-9999	-0.043	27	27
CSNK1G3	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.027	0.007	-9999	-10000	0	0
ZFAND5	0.085	0.067	-9999	-10000	0	0
SFN	-0.012	0.061	-9999	-10000	0	0
CDK2	0.011	0.037	-9999	-10000	0	0
FOXO3A/14-3-3	0.029	0.047	-9999	-10000	0	0
CREBBP	0.021	0.002	-9999	-10000	0	0
FBXO32	-0.52	0.64	-9999	-1.2	27	27
BCL6	-0.075	0.24	-9999	-0.75	3	3
RALB	0.017	0.001	-9999	-10000	0	0
RALA	0.017	0.001	-9999	-10000	0	0
YWHAH	0.016	0	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

Figure S46. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S46. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.055	0.068	-10000	0	-10000	0	0
UGCG	0.015	0.027	-10000	0	-10000	0	0
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.035	0.18	-10000	0	-0.37	8	8
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	0.018	0.027	-10000	0	-10000	0	0
mol:DAG	0	0.002	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.1	0.17	-10000	0	-0.42	8	8
FRAP1	-0.059	0.24	-10000	0	-0.5	8	8
FOXO3	0.013	0.14	-10000	0	-0.56	1	1
AKT1	0.005	0.15	-10000	0	-0.61	1	1
GAB2	0.013	0.005	-10000	0	-10000	0	0
SMPD1	0.015	0.027	-10000	0	-10000	0	0
SGMS1	0.015	0.027	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.001	0.12	-10000	0	-0.85	1	1
CALM1	0.016	0	-10000	0	-10000	0	0
cell proliferation	0.023	0.061	-10000	0	-10000	0	0
EIF3A	0.016	0	-10000	0	-10000	0	0
PI3K	0.003	0.13	-10000	0	-0.94	1	1
RPS6KB1	-0.053	0.11	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.002	-10000	0	-10000	0	0
natural killer cell activation	-0.002	0.004	-10000	0	-10000	0	0
JAK3	0.016	0.004	-10000	0	-10000	0	0
PIK3R1	0.003	0.096	-10000	0	-0.69	1	1
JAK1	0.016	0.004	-10000	0	-10000	0	0
NFKB1	0.016	0	-10000	0	-10000	0	0
MYC	0.017	0.13	-10000	0	-0.49	1	1
MYB	-0.39	0.57	-10000	0	-1.2	19	19
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.021	0.1	-10000	0	-0.48	1	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.031	0.1	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.024	0.1	-10000	0	-0.47	1	1
Rac1/GDP	0.008	0.11	-10000	0	-0.78	1	1
T cell proliferation	0.03	0.096	-10000	0	-0.44	1	1
SHC1	0.013	0.005	-10000	0	-10000	0	0
RAC1	0.015	0.001	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.019	0.034	-10000	0	-0.065	19	19
PRKCZ	0.03	0.098	-10000	0	-0.46	1	1
NF kappa B1 p50/RelA	-0.098	0.17	-10000	0	-0.42	8	8
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.039	0.077	-10000	0	-0.47	1	1
HSP90AA1	0.016	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL2RA	0.013	0.005	-10000	0	-10000	0	0
IL2RB	0.016	0.004	-10000	0	-10000	0	0
TERT	0.016	0	-10000	0	-10000	0	0
E2F1	-0.13	0.22	-10000	0	-0.43	19	19
SOS1	0.013	0.005	-10000	0	-10000	0	0
RPS6	0.016	0	-10000	0	-10000	0	0
mol:cAMP	0.009	0.016	0.031	19	-10000	0	19
PTPN11	0.012	0.007	-10000	0	-10000	0	0
IL2RG	0.016	0.004	-10000	0	-10000	0	0
actin cytoskeleton organization	0.03	0.096	-10000	0	-0.44	1	1
GRB2	0.013	0.005	-10000	0	-10000	0	0
IL2	0.016	0.004	-10000	0	-10000	0	0
PIK3CA	0.003	0.096	-10000	0	-0.69	1	1
Rac1/GTP	0.008	0.11	-10000	0	-0.76	1	1
LCK	0.01	0.031	-10000	0	-10000	0	0
BCL2	-0.19	0.44	-10000	0	-0.86	16	16

×

Regulation of p38-alpha and p38-beta

Figure S47. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S47. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.021	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.009	0.058	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.016	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.15	0.13	-9999	-0.24	36	36
response to UV	0	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.016	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
MAP3K12	0.013	0.022	-9999	-10000	0	0
FGR	0.016	0	-9999	-10000	0	0
p38 alpha/TAB1	0.042	0.025	-9999	-10000	0	0
PRKG1	0.016	0	-9999	-10000	0	0
DUSP8	0.016	0	-9999	-10000	0	0
PGK/cGMP/p38 alpha	0.001	0.014	-9999	-10000	0	0
apoptosis	0.019	0.021	-9999	-10000	0	0
RAL/GTP	0.021	0	-9999	-10000	0	0
LYN	0.013	0.022	-9999	-10000	0	0
DUSP1	-0.3	0.35	-9999	-0.69	24	24
PAK1	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.04	0	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.016	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.021	0	-9999	-10000	0	0
MAPK11	0.024	0.037	-9999	-10000	0	0
BLK	0.013	0.022	-9999	-10000	0	0
HCK	0.002	0.095	-9999	-0.69	1	1
MAP2K3	0.016	0	-9999	-10000	0	0
DUSP16	0.016	0	-9999	-10000	0	0
DUSP10	0.016	0	-9999	-10000	0	0
TRAF6/MEKK3	0.02	0	-9999	-10000	0	0
MAP3K7IP1	0.016	0	-9999	-10000	0	0
MAPK14	0.036	0.028	-9999	-10000	0	0
positive regulation of innate immune response	0.032	0.041	-9999	-10000	0	0
LCK	0.01	0.031	-9999	-10000	0	0
p38alpha-beta/MKP7	0.04	0.04	-9999	-10000	0	0
p38alpha-beta/MKP5	0.04	0.04	-9999	-10000	0	0
PGK/cGMP	0.012	0	-9999	-10000	0	0
PAK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.11	0.17	-9999	-0.31	17	17
CDC42	0.016	0	-9999	-10000	0	0
RALB	0.016	0	-9999	-10000	0	0
RALA	0.016	0	-9999	-10000	0	0
PAK3	-0.46	0.33	-9999	-0.69	36	36

×

IL27-mediated signaling events

Figure S48. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S48. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.026	0.001	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.06	0.061	-10000	0	-10000	0	0
IL27/IL27R/JAK1	0.2	0.15	-10000	0	-0.47	1	1
TBX21	0.097	0.25	-10000	0	-0.49	8	8
IL12B	0.017	0.001	-10000	0	-10000	0	0
IL12A	0.011	0.014	-10000	0	-10000	0	0
IL6ST	0.009	0.098	-10000	0	-0.71	1	1
IL27RA/JAK1	0.049	0.026	-10000	0	-10000	0	0
IL27	0.023	0.006	-10000	0	-10000	0	0
TYK2	0.018	0.005	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.091	0.15	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.06	0.061	-10000	0	-10000	0	0
T cell proliferation during immune response	-0.06	0.061	-10000	0	-10000	0	0
MAPKKK cascade	0.06	0.061	-10000	0	-10000	0	0
STAT3	0.016	0	-10000	0	-10000	0	0
STAT2	0.016	0	-10000	0	-10000	0	0
STAT1	0.013	0.037	-10000	0	-10000	0	0
IL12RB1	0.016	0.001	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.15	0.14	-10000	0	-0.49	1	1
IL27/IL27R/JAK2/TYK2	0.06	0.061	-10000	0	-10000	0	0
positive regulation of T cell mediated cytotoxicity	0.06	0.061	-10000	0	-10000	0	0
STAT1 (dimer)	0.37	0.27	0.5	43	-0.68	1	44
JAK2	0.016	0.004	-10000	0	-10000	0	0
JAK1	0.021	0.004	-10000	0	-10000	0	0
STAT2 (dimer)	0.064	0.058	-10000	0	-10000	0	0
T cell proliferation	-0.055	0.18	-10000	0	-0.38	2	2
IL12/IL12R/TYK2/JAK2	0.061	0.02	-10000	0	-10000	0	0
IL17A	-0.091	0.15	-10000	0	-10000	0	0
mast cell activation	-0.06	0.061	-10000	0	-10000	0	0
IFNG	0.021	0.013	-10000	0	-10000	0	0
T cell differentiation	-0.001	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	0.064	0.058	-10000	0	-10000	0	0
STAT5A (dimer)	0.064	0.058	-10000	0	-10000	0	0
STAT4 (dimer)	0.064	0.058	-10000	0	-10000	0	0
STAT4	0.016	0	-10000	0	-10000	0	0
T cell activation	-0.009	0.002	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.004	0.059	-10000	0	-10000	0	0
GATA3	-1.1	0.33	-10000	0	-1.2	50	50
IL18	0.013	0	-10000	0	-10000	0	0
positive regulation of mast cell cytokine production	0.063	0.057	-10000	0	-10000	0	0
IL27/EBI3	0.038	0.012	-10000	0	-10000	0	0
IL27RA	-0.001	0.005	-10000	0	-10000	0	0
IL6	-0.2	0.33	-10000	0	-0.68	17	17
STAT5A	0.016	0	-10000	0	-10000	0	0
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.001	0.004	-10000	0	-10000	0	0
IL1B	-0.007	0.1	-10000	0	-0.52	2	2
EBI3	0.022	0.006	-10000	0	-10000	0	0
TNF	0.007	0.024	-10000	0	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

Figure S49. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S49. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.058	0.14	-9999	-0.85	1	1
NCK1/PAK1/Dok-R	-0.017	0.086	-9999	-0.46	2	2
NCK1/Dok-R	0.053	0.18	-9999	-0.89	2	2
PIK3CA	0.002	0.095	-9999	-0.69	1	1
mol:beta2-estradiol	-0.013	0.005	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
SHC1	0.017	0.001	-9999	-10000	0	0
Rac/GDP	0.012	0	-9999	-10000	0	0
F2	0.001	0.006	-9999	-10000	0	0
TNIP2	0.016	0	-9999	-10000	0	0
NF kappa B/RelA	-0.014	0.12	-9999	-0.88	1	1
FN1	0.01	0.031	-9999	-10000	0	0
PLD2	0.061	0.15	-9999	-0.98	1	1
PTPN11	0.016	0	-9999	-10000	0	0
GRB14	-0.022	0.11	-9999	-0.69	1	1
ELK1	0.07	0.14	-9999	-0.9	1	1
GRB7	0.01	0.031	-9999	-10000	0	0
PAK1	0.016	0	-9999	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.014	0.13	-9999	-0.92	1	1
CDKN1A	-0.003	0.099	-9999	-0.62	1	1
ITGA5	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
RasGAP/Dok-R	0.059	0.16	-9999	-0.94	1	1
CRK	0.016	0	-9999	-10000	0	0
mol:NO	0.065	0.11	-9999	-0.63	1	1
PLG	0.059	0.15	-9999	-0.98	1	1
mol:GDP	0	0	-9999	-10000	0	0
chemokinesis	0.049	0.13	-9999	-0.81	1	1
GRB2	0.016	0	-9999	-10000	0	0
PIK3R1	0.004	0.095	-9999	-0.69	1	1
ANGPT2	-0.16	0.068	-9999	-0.43	2	2
BMX	-0.17	0.24	-9999	-1.3	1	1
ANGPT1	0.044	0.024	-9999	-10000	0	0
tube development	-0.012	0.11	-9999	-0.71	1	1
ANGPT4	0.015	0.001	-9999	-10000	0	0
response to hypoxia	0.005	0.01	-9999	-10000	0	0
Tie2/Ang1/GRB14	0.05	0.16	-9999	-0.99	1	1
alpha5/beta1 Integrin	0.023	0	-9999	-10000	0	0
FGF2	-0.48	0.32	-9999	-0.69	38	38
STAT5A (dimer)	-0.004	0.12	-9999	-0.81	1	1
mol:L-citrulline	0.065	0.11	-9999	-0.63	1	1
AGTR1	-0.67	0.095	-9999	-0.69	53	53
MAPK14	0.037	0.16	-9999	-1.1	1	1
Tie2/SHP2	-0.021	0.14	-9999	-1	1	1
TEK	0.035	0.17	-9999	-1.1	1	1
RPS6KB1	0.046	0.14	-9999	-0.83	1	1
Angiotensin II/AT1	-0.51	0.072	-9999	-0.52	53	53
Tie2/Ang1/GRB2	0.06	0.15	-9999	-0.99	1	1
MAPK3	0.067	0.14	-9999	-0.91	1	1
MAPK1	0.067	0.14	-9999	-0.91	1	1
Tie2/Ang1/GRB7	0.059	0.15	-9999	-0.99	1	1
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	0.061	0.15	-9999	-0.98	1	1
PI3K	0.037	0.16	-9999	-0.98	1	1
FES	0.036	0.16	-9999	-1.1	1	1
Crk/Dok-R	0.059	0.16	-9999	-0.94	1	1
Tie2/Ang1/ABIN2	0.06	0.15	-9999	-0.99	1	1
blood circulation	0	0	-9999	-10000	0	0
negative regulation of caspase activity	0.059	0.13	-9999	-0.76	1	1
STAT5A	0.016	0	-9999	-10000	0	0
mol:ROS	0	0	-9999	-10000	0	0
PTK2	0.046	0.14	-9999	-0.83	1	1
Tie2/Ang2	-0.024	0.14	-9999	-0.98	1	1
Tie2/Ang1	0.056	0.15	-9999	-1	1	1
FOXO1	0.075	0.13	-9999	-0.76	1	1
ELF1	0.012	0.096	-9999	-0.68	1	1
ELF2	0.058	0.15	-9999	-1	1	1
mol:Choline	0.061	0.14	-9999	-0.94	1	1
cell migration	-0.008	0.043	-9999	-0.22	2	2
FYN	-0.014	0.12	-9999	-0.81	1	1
DOK2	0.002	0.095	-9999	-0.69	1	1
negative regulation of cell cycle	-0.002	0.091	-9999	-0.57	1	1
ETS1	0.028	0.004	-9999	-10000	0	0
PXN	0.053	0.12	-9999	-0.68	1	1
ITGB1	0.016	0	-9999	-10000	0	0
NOS3	0.065	0.12	-9999	-0.72	1	1
RAC1	0.016	0	-9999	-10000	0	0
TNF	0.019	0.037	-9999	-10000	0	0
MAPKKK cascade	0.061	0.14	-9999	-0.94	1	1
RASA1	0.016	0	-9999	-10000	0	0
Tie2/Ang1/Shc	0.062	0.15	-9999	-1	1	1
NCK1	0.002	0.095	-9999	-0.69	1	1
vasculogenesis	0.064	0.1	-9999	-0.56	1	1
mol:Phosphatidic acid	0.061	0.14	-9999	-0.94	1	1
mol:Angiotensin II	0.001	0	-9999	-10000	0	0
mol:NADP	0.065	0.11	-9999	-0.63	1	1
Rac1/GTP	-0.012	0.12	-9999	-0.77	1	1
MMP2	0.06	0.15	-9999	-0.98	1	1

×

Neurotrophic factor-mediated Trk receptor signaling

Figure S50. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S50. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.016	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	0.037	0.006	-10000	0	-10000	0	0
NT3 (dimer)/TRKC	0.021	0.014	-10000	0	-10000	0	0
NT3 (dimer)/TRKB	-0.35	0.18	-10000	0	-0.44	44	44
SHC/Grb2/SOS1/GAB1/PI3K	0.022	0.15	-10000	0	-1	1	1
RAPGEF1	0.016	0	-10000	0	-10000	0	0
BDNF	-0.031	0.11	-10000	0	-0.69	1	1
PIK3CA	0.002	0.095	-10000	0	-0.69	1	1
DYNLT1	0.016	0	-10000	0	-10000	0	0
NTRK1	0.013	0.022	-10000	0	-10000	0	0
NTRK2	-0.56	0.27	-10000	0	-0.69	44	44
NTRK3	0.016	0	-10000	0	-10000	0	0
NT-4/5 (dimer)/TRKB	-0.36	0.18	-10000	0	-0.44	44	44
neuron apoptosis	0.18	0.14	0.52	5	-10000	0	5
SHC 2-3/Grb2	-0.19	0.16	-10000	0	-0.58	5	5
SHC1	0.016	0	-10000	0	-10000	0	0
SHC2	-0.16	0.13	-10000	0	-0.6	3	3
SHC3	-0.16	0.15	-10000	0	-0.71	3	3
STAT3 (dimer)	0.023	0.011	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	0.029	0.016	-10000	0	-10000	0	0
RIN/GDP	0.045	0.017	-10000	0	-10000	0	0
GIPC1	0.013	0.022	-10000	0	-10000	0	0
KRAS	0.016	0	-10000	0	-10000	0	0
DNAJA3	-0.006	0.041	-10000	0	-0.3	1	1
RIN/GTP	0.012	0	-10000	0	-10000	0	0
CCND1	0.032	0.019	-10000	0	-10000	0	0
MAGED1	0.016	0	-10000	0	-10000	0	0
PTPN11	0.016	0	-10000	0	-10000	0	0
RICS	0.016	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.032	0	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.011	0.064	-10000	0	-0.44	1	1
TRKA/NEDD4-2	0.001	0.1	-10000	0	-0.51	2	2
ELMO1	0.016	0	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0.021	0	-10000	0	-10000	0	0
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.016	0	-10000	0	-10000	0	0
DOCK1	0.016	0	-10000	0	-10000	0	0
GAB2	0.016	0	-10000	0	-10000	0	0
RIT2	0.016	0	-10000	0	-10000	0	0
RIT1	0.016	0	-10000	0	-10000	0	0
FRS2	0.016	0	-10000	0	-10000	0	0
DNM1	0.002	0.095	-10000	0	-0.69	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.016	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.006	0.04	-10000	0	-0.3	1	1
mol:GDP	0.051	0.022	-10000	0	-10000	0	0
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.012	0	-10000	0	-10000	0	0
RIT1/GDP	0.045	0.017	-10000	0	-10000	0	0
TIAM1	0.016	0	-10000	0	-10000	0	0
PIK3R1	0.002	0.095	-10000	0	-0.69	1	1
BDNF (dimer)/TRKB	-0.37	0.18	-10000	0	-0.45	45	45
KIDINS220/CRKL/C3G	0.023	0	-10000	0	-10000	0	0
SHC/RasGAP	0.023	0	-10000	0	-10000	0	0
FRS2 family/SHP2	0.032	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.032	0.058	-10000	0	-0.39	1	1
RIT1/GTP	0.012	0	-10000	0	-10000	0	0
NT3 (dimer)	0.013	0.022	-10000	0	-10000	0	0
RAP1/GDP	-0.011	0.044	-10000	0	-0.21	1	1
KIDINS220/CRKL	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.031	0.11	-10000	0	-0.69	1	1
ubiquitin-dependent protein catabolic process	0.002	0.088	-10000	0	-0.44	2	2
Schwann cell development	-0.043	0.02	-10000	0	-10000	0	0
EHD4	0.016	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.04	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.046	0	-10000	0	-10000	0	0
RAP1B	0.016	0	-10000	0	-10000	0	0
RAP1A	-0.024	0.16	-10000	0	-0.69	3	3
CDC42/GTP	-0.27	0.12	-10000	0	-0.38	11	11
ABL1	0.016	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.023	0	-10000	0	-10000	0	0
Rap1/GTP	-0.13	0.1	-10000	0	-0.42	3	3
STAT3	0.023	0.011	-10000	0	-10000	0	0
axon guidance	-0.26	0.12	-10000	0	-0.36	11	11
MAPK3	0.019	0.058	-10000	0	-0.4	1	1
MAPK1	0.019	0.058	-10000	0	-0.4	1	1
CDC42/GDP	0.045	0.017	-10000	0	-10000	0	0
NTF3	0.013	0.022	-10000	0	-10000	0	0
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.011	0.064	-10000	0	-0.44	1	1
PI3K	0.005	0.13	-10000	0	-0.94	1	1
FRS3	0.016	0	-10000	0	-10000	0	0
FAIM	0.002	0.095	-10000	0	-0.69	1	1
GAB1	0.002	0.095	-10000	0	-0.69	1	1
RASGRF1	-0.014	0.043	-10000	0	-0.3	1	1
SOS1	0.016	0	-10000	0	-10000	0	0
MCF2L	0.03	0.012	-10000	0	-10000	0	0
RGS19	0.016	0	-10000	0	-10000	0	0
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	0.06	0.02	-10000	0	-10000	0	0
Rac1/GDP	0.045	0.017	-10000	0	-10000	0	0
NGF (dimer)/TRKA/GRIT	0.02	0.012	-10000	0	-10000	0	0
neuron projection morphogenesis	0.034	0.039	-10000	0	-10000	0	0
NGF (dimer)/TRKA/NEDD4-2	0.002	0.088	-10000	0	-0.44	2	2
MAP2K1	0.036	0.054	-10000	0	-0.36	1	1
NGFR	0.016	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/GIPC/GAIP	0.028	0.044	-10000	0	-0.28	1	1
RAS family/GTP/PI3K	0.023	0.083	-10000	0	-0.58	1	1
FRS2 family/SHP2/GRB2/SOS1	0.046	0	-10000	0	-10000	0	0
NRAS	0.013	0.022	-10000	0	-10000	0	0
GRB2/SOS1	0.023	0	-10000	0	-10000	0	0
PRKCI	0.013	0.022	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.058	0.11	-10000	0	-0.81	1	1
RASA1	0.016	0	-10000	0	-10000	0	0
TRKA/c-Abl	0.021	0.014	-10000	0	-10000	0	0
SQSTM1	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.33	0.17	-10000	0	-0.41	45	45
NGF (dimer)/TRKA/p62/Atypical PKCs	0.025	0.014	-10000	0	-10000	0	0
MATK	0.002	0.095	-10000	0	-0.69	1	1
NEDD4L	-0.011	0.13	-10000	0	-0.69	2	2
RAS family/GDP	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.006	0.044	-10000	0	-0.33	1	1
Rac1/GTP	-0.003	0.021	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family	0.046	0	-10000	0	-10000	0	0

×

Regulation of Androgen receptor activity

Figure S51. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S51. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.024	0.014	-9999	-10000	0	0
SMARCC1	0.008	0.019	-9999	-10000	0	0
REL	0.001	0.095	-9999	-0.69	1	1
HDAC7	0.033	0.089	-9999	-10000	0	0
JUN	0.003	0.095	-9999	-0.69	1	1
EP300	0.016	0	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
KAT5	0	0	-9999	-10000	0	0
MAPK14	0.012	0.038	-9999	-10000	0	0
FOXO1	0.016	0	-9999	-10000	0	0
T-DHT/AR	0.044	0.097	-9999	-10000	0	0
MAP2K6	-0.007	0.056	-9999	-10000	0	0
BRM/BAF57	0.015	0.072	-9999	-0.51	1	1
MAP2K4	0.016	0.005	-9999	-10000	0	0
SMARCA2	0.003	0.095	-9999	-0.69	1	1
PDE9A	-0.029	0.15	-9999	-1	1	1
NCOA2	0.016	0	-9999	-10000	0	0
CEBPA	0.015	0	-9999	-10000	0	0
EHMT2	0.007	0.037	-9999	-10000	0	0
cell proliferation	0.067	0.1	-9999	-0.39	1	1
NR0B1	-0.01	0.1	-9999	-0.69	1	1
EGR1	-0.35	0.35	-9999	-0.69	28	28
RXRs/9cRA	0.024	0.058	-9999	-0.4	1	1
AR/RACK1/Src	0.05	0.049	-9999	-10000	0	0
AR/GR	-0.29	0.2	-9999	-0.4	40	40
GNB2L1	0.016	0	-9999	-10000	0	0
PKN1	0.013	0.022	-9999	-10000	0	0
RCHY1	-0.037	0.18	-9999	-0.69	4	4
epidermal growth factor receptor activity	0.001	0	-9999	-10000	0	0
MAPK8	0.028	0.012	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.05	0.051	-9999	-10000	0	0
SRC	0.038	0.032	-9999	-10000	0	0
NR3C1	-0.49	0.32	-9999	-0.69	39	39
KLK3	-0.062	0.093	-9999	-10000	0	0
APPBP2	0.016	0.006	-9999	-10000	0	0
TRIM24	0.017	0	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.013	0.032	-9999	-10000	0	0
TMPRSS2	-0.12	0.34	-9999	-1.1	6	6
RXRG	0.016	0	-9999	-10000	0	0
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.003	0.095	-9999	-0.69	1	1
RXRB	0.016	0	-9999	-10000	0	0
CARM1	0.013	0.022	-9999	-10000	0	0
NR2C2	0.016	0	-9999	-10000	0	0
KLK2	0.066	0.042	-9999	-10000	0	0
AR	0.014	0.093	-9999	-0.31	4	4
SENP1	0.013	0.022	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
MDM2	0.011	0.022	-9999	-10000	0	0
SRY	0.014	0.002	-9999	-10000	0	0
GATA2	-0.012	0.061	-9999	-10000	0	0
MYST2	0.015	0	-9999	-10000	0	0
HOXB13	-0.07	0.081	-9999	-10000	0	0
T-DHT/AR/RACK1/Src	0.046	0.05	-9999	-10000	0	0
positive regulation of transcription	-0.012	0.061	-9999	-10000	0	0
DNAJA1	0.012	0.025	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.003	0.1	-9999	-0.36	4	4
NCOA1	0.02	0.005	-9999	-10000	0	0
SPDEF	-0.12	0.27	-9999	-0.69	10	10
T-DHT/AR/TIF2	0.047	0.036	-9999	-10000	0	0
T-DHT/AR/Hsp90	0.035	0.051	-9999	-10000	0	0
GSK3B	0.016	0.002	-9999	-10000	0	0
NR2C1	0.015	0	-9999	-10000	0	0
mol:T-DHT	0.031	0.035	-9999	-10000	0	0
SIRT1	0.016	0	-9999	-10000	0	0
ZMIZ2	0.014	0	-9999	-10000	0	0
POU2F1	0.028	0.011	-9999	-10000	0	0
T-DHT/AR/DAX-1	0.025	0.073	-9999	-0.33	1	1
CREBBP	0.016	0	-9999	-10000	0	0
SMARCE1	0.016	0	-9999	-10000	0	0

×

Coregulation of Androgen receptor activity

Figure S52. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S52. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.035	0.18	-9999	-0.69	4	4
SVIL	0.004	0.095	-9999	-0.69	1	1
ZNF318	0.012	0	-9999	-10000	0	0
JMJD2C	0.024	0	-9999	-10000	0	0
T-DHT/AR/Ubc9	-0.015	0.14	-9999	-0.5	4	4
CARM1	0.013	0.022	-9999	-10000	0	0
PRDX1	0.015	0	-9999	-10000	0	0
PELP1	0.012	0.022	-9999	-10000	0	0
CTNNB1	0.017	0	-9999	-10000	0	0
AKT1	0.014	0	-9999	-10000	0	0
PTK2B	0.017	0	-9999	-10000	0	0
MED1	0.014	0	-9999	-10000	0	0
MAK	-0.004	0.047	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.017	0	-9999	-10000	0	0
GSN	-0.061	0.22	-9999	-0.69	6	6
NCOA2	0.016	0	-9999	-10000	0	0
NCOA6	0.018	0	-9999	-10000	0	0
DNA-PK	0.026	0.012	-9999	-10000	0	0
NCOA4	0.003	0.095	-9999	-0.69	1	1
PIAS3	0.014	0.022	-9999	-10000	0	0
cell proliferation	-0.014	0.025	-9999	-10000	0	0
XRCC5	0.015	0	-9999	-10000	0	0
UBE3A	0.018	0	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.025	0.14	-9999	-0.51	4	4
FHL2	-0.033	0.27	-9999	-1.1	3	3
RANBP9	0.018	0	-9999	-10000	0	0
JMJD1A	0.007	0.058	-9999	-0.31	1	1
CDK6	-0.024	0.16	-9999	-0.69	3	3
TGFB1I1	0.004	0.095	-9999	-0.69	1	1
T-DHT/AR/CyclinD1	-0.015	0.15	-9999	-0.52	4	4
XRCC6	0.015	0	-9999	-10000	0	0
T-DHT/AR	-0.011	0.17	-9999	-0.56	4	4
CTDSP1	0.016	0	-9999	-10000	0	0
CTDSP2	0.013	0	-9999	-10000	0	0
BRCA1	0.014	0.022	-9999	-10000	0	0
TCF4	0.014	0	-9999	-10000	0	0
CDKN2A	-0.052	0.08	-9999	-10000	0	0
SRF	0.016	0.031	-9999	-10000	0	0
NKX3-1	-0.039	0.094	-9999	-0.34	3	3
KLK3	0.018	0.034	-9999	-10000	0	0
TMF1	0.016	0	-9999	-10000	0	0
HNRNPA1	0.014	0	-9999	-10000	0	0
AOF2	0.018	0	-9999	-10000	0	0
APPL1	0.023	0	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.017	0.14	-9999	-0.51	4	4
AR	-0.04	0.2	-9999	-0.73	4	4
UBA3	0.001	0	-9999	-10000	0	0
PATZ1	0.011	0.022	-9999	-10000	0	0
PAWR	0.016	0	-9999	-10000	0	0
PRKDC	0.012	0.022	-9999	-10000	0	0
PA2G4	0.011	0.022	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.014	0.13	-9999	-0.47	4	4
RPS6KA3	0.018	0	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.023	0.16	-9999	-0.49	5	5
LATS2	0.014	0	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.015	0.13	-9999	-0.47	4	4
Cyclin D3/CDK11 p58	0.011	0	-9999	-10000	0	0
VAV3	-0.035	0.18	-9999	-0.69	4	4
KLK2	0.025	0.062	-9999	-10000	0	0
CASP8	0.015	0	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.003	0.13	-9999	-0.46	4	4
TMPRSS2	-0.087	0.36	-9999	-1.1	6	6
CCND1	0.013	0.022	-9999	-10000	0	0
PIAS1	0.018	0	-9999	-10000	0	0
mol:T-DHT	-0.003	0.025	-9999	-0.067	7	7
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.016	0.022	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.042	0.17	-9999	-0.47	7	7
CMTM2	0.015	0	-9999	-10000	0	0
SNURF	0	0	-9999	-10000	0	0
ZMIZ1	0.014	0.022	-9999	-10000	0	0
CCND3	0.015	0	-9999	-10000	0	0
TGIF1	0.008	0.031	-9999	-10000	0	0
FKBP4	0.018	0	-9999	-10000	0	0

×

Osteopontin-mediated events

Figure S53. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S53. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.033	0.037	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.06	0.034	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin/Src	-0.01	0.049	-9999	-10000	0	0
AP1	-0.12	0.19	-9999	-0.39	4	4
ILK	0.02	0.041	-9999	-10000	0	0
bone resorption	0.047	0.033	-9999	-10000	0	0
PTK2B	0.016	0	-9999	-10000	0	0
PYK2/p130Cas	0.053	0.028	-9999	-10000	0	0
ITGAV	0.02	0.001	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.023	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	0.036	0.031	-9999	-10000	0	0
MAP3K1	0.012	0.066	-9999	-0.37	1	1
JUN	0.003	0.095	-9999	-0.69	1	1
MAPK3	0.035	0.04	-9999	-10000	0	0
MAPK1	0.035	0.04	-9999	-10000	0	0
Rac1/GDP	0.012	0	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	0.022	0.063	-9999	-0.34	1	1
ITGB3	0.012	0.037	-9999	-10000	0	0
NFKBIA	0.046	0.038	-9999	-10000	0	0
FOS	-0.32	0.35	-9999	-0.69	26	26
CD44	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
PLAU	0.037	0.049	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.016	0.023	-9999	-10000	0	0
BCAR1	0.016	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	0.027	0.024	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
SYK	0.015	0.042	-9999	-10000	0	0
VAV3	-0.009	0.11	-9999	-0.38	4	4
MAP3K14	0.022	0.042	-9999	-10000	0	0
ROCK2	0.016	0	-9999	-10000	0	0
SPP1	-0.047	0.078	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
Rac1/GTP	0.003	0.1	-9999	-0.34	4	4
MMP2	-0.099	0.16	-9999	-0.42	1	1

×

Syndecan-2-mediated signaling events

Figure S54. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S54. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.014	0.064	-9999	-0.43	1	1
EPHB2	0	0.047	-9999	-10000	0	0
Syndecan-2/TACI	0.018	0.063	-9999	-0.43	1	1
LAMA1	-0.009	0.058	-9999	-10000	0	0
Syndecan-2/alpha2 ITGB1	0.013	0.11	-9999	-0.37	4	4
HRAS	0.016	0	-9999	-10000	0	0
Syndecan-2/CASK	0.006	0.062	-9999	-0.44	1	1
ITGA5	0.016	0	-9999	-10000	0	0
BAX	0.03	0.063	-9999	-0.38	1	1
EPB41	0.016	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0.016	0.057	-9999	-0.39	1	1
LAMA3	-0.024	0.16	-9999	-0.69	3	3
EZR	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.53	0.29	-9999	-0.69	42	42
Syndecan-2/MMP2	0.016	0.063	-9999	-0.43	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.023	0	-9999	-10000	0	0
dendrite morphogenesis	0.01	0.066	-9999	-0.43	1	1
Syndecan-2/GM-CSF	0.018	0.063	-9999	-0.43	1	1
determination of left/right symmetry	0.01	0.072	-9999	-0.51	1	1
Syndecan-2/PKC delta	0.018	0.063	-9999	-0.43	1	1
GNB2L1	0.016	0	-9999	-10000	0	0
MAPK3	0.026	0.057	-9999	-0.39	1	1
MAPK1	0.026	0.057	-9999	-0.39	1	1
Syndecan-2/RACK1	0.026	0.054	-9999	-0.37	1	1
NF1	0.016	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.01	0.072	-9999	-0.51	1	1
ITGA2	0.016	0	-9999	-10000	0	0
MAPK8	0.025	0.065	-9999	-0.43	1	1
Syndecan-2/alpha2/beta1 Integrin	0.034	0.055	-9999	-0.36	1	1
Syndecan-2/Kininogen	0.016	0.063	-9999	-0.43	1	1
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.032	0.052	-9999	-0.34	1	1
Syndecan-2/CASK/Protein 4.1	0.016	0.057	-9999	-0.4	1	1
extracellular matrix organization	0.018	0.062	-9999	-0.43	1	1
actin cytoskeleton reorganization	0.014	0.064	-9999	-0.43	1	1
Syndecan-2/Caveolin-2/Ras	-0.31	0.19	-9999	-0.4	42	42
Syndecan-2/Laminin alpha3	-0.008	0.12	-9999	-0.44	4	4
Syndecan-2/RasGAP	0.033	0.052	-9999	-0.34	1	1
alpha5/beta1 Integrin	0.023	0	-9999	-10000	0	0
PRKCD	0.016	0	-9999	-10000	0	0
Syndecan-2 dimer	0.01	0.066	-9999	-0.43	1	1
GO:0007205	0.002	0.008	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.041	0.051	-9999	-0.33	1	1
RHOA	0.016	0	-9999	-10000	0	0
SDCBP	0.016	0	-9999	-10000	0	0
TNFRSF13B	0.016	0	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
alpha2/beta1 Integrin	0.023	0	-9999	-10000	0	0
Syndecan-2/Synbindin	0.018	0.063	-9999	-0.43	1	1
TGFB1	0.016	0	-9999	-10000	0	0
CASP3	0.026	0.057	-9999	-0.39	1	1
FN1	0.01	0.031	-9999	-10000	0	0
Syndecan-2/IL8	-0.009	0.071	-9999	-0.43	1	1
SDC2	0.01	0.073	-9999	-0.51	1	1
KNG1	0.013	0.022	-9999	-10000	0	0
Syndecan-2/Neurofibromin	0.018	0.063	-9999	-0.43	1	1
TRAPPC4	0.016	0	-9999	-10000	0	0
CSF2	0.016	0	-9999	-10000	0	0
Syndecan-2/TGFB1	0.018	0.063	-9999	-0.43	1	1
Syndecan-2/Syntenin/PI-4-5-P2	0.016	0.057	-9999	-0.4	1	1
Syndecan-2/Ezrin	0.016	0.057	-9999	-0.4	1	1
PRKACA	0.026	0.057	-9999	-0.39	1	1
angiogenesis	-0.009	0.071	-9999	-0.43	1	1
MMP2	0.013	0.022	-9999	-10000	0	0
IL8	-0.036	0.076	-9999	-10000	0	0
calcineurin-NFAT signaling pathway	0.018	0.062	-9999	-0.43	1	1

×

Cellular roles of Anthrax toxin

Figure S55. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S55. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.016	0	-10000	0	-10000	0	0
ANTXR2	-0.024	0.16	-10000	0	-0.69	3	3
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.005	0.02	-10000	0	-0.088	3	3
monocyte activation	-0.1	0.2	-10000	0	-0.42	15	15
MAP2K2	-0.002	0.008	-10000	0	-10000	0	0
MAP2K1	-0.004	0.017	-10000	0	-10000	0	0
MAP2K7	-0.004	0.017	-10000	0	-10000	0	0
MAP2K6	-0.013	0.025	-10000	0	-10000	0	0
CYAA	-0.006	0.091	-10000	0	-0.38	3	3
MAP2K4	-0.004	0.017	-10000	0	-10000	0	0
IL1B	-0.02	0.089	-10000	0	-0.44	2	2
Channel	-0.004	0.098	-10000	0	-0.41	3	3
NLRP1	-0.004	0.017	-10000	0	-10000	0	0
CALM1	0.016	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.006	0.023	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.005	0.02	0.088	3	-10000	0	3
MAPK3	-0.004	0.017	-10000	0	-10000	0	0
MAPK1	-0.004	0.017	-10000	0	-10000	0	0
PGR	-0.037	0.059	-10000	0	-0.27	2	2
PA/Cellular Receptors	-0.005	0.11	-10000	0	-0.44	3	3
apoptosis	-0.005	0.02	-10000	0	-0.088	3	3
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.003	0.092	-10000	0	-0.38	3	3
macrophage activation	0.017	0.019	-10000	0	-10000	0	0
TNF	0.006	0.037	-10000	0	-10000	0	0
VCAM1	-0.1	0.2	-10000	0	-0.42	15	15
platelet activation	-0.006	0.023	-10000	0	-10000	0	0
MAPKKK cascade	-0.01	0.021	-10000	0	-10000	0	0
IL18	-0.006	0.034	-10000	0	-10000	0	0
negative regulation of macrophage activation	-0.005	0.02	-10000	0	-0.088	3	3
LEF	-0.005	0.02	-10000	0	-0.088	3	3
CASP1	-0.023	0.031	-10000	0	-10000	0	0
mol:cAMP	-0.006	0.023	-10000	0	-10000	0	0
necrosis	-0.005	0.02	-10000	0	-0.088	3	3
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.003	0.093	-10000	0	-0.38	3	3
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)

Figure S56. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S56. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.021	0.014	-10000	0	-10000	0	0
CRKL	0.036	0.058	-10000	0	-0.38	1	1
mol:PIP3	-0.012	0.083	0.59	1	-10000	0	1
AKT1	0.008	0.054	0.4	1	-10000	0	1
PTK2B	0.016	0	-10000	0	-10000	0	0
RAPGEF1	0.043	0.055	-10000	0	-0.36	1	1
RANBP10	0.016	0	-10000	0	-10000	0	0
PIK3CA	0.002	0.095	-10000	0	-0.69	1	1
HGF/MET/SHIP2	0.029	0.016	-10000	0	-10000	0	0
MAP3K5	0.039	0.085	-10000	0	-0.31	3	3
HGF/MET/CIN85/CBL/ENDOPHILINS	0.037	0.015	-10000	0	-10000	0	0
AP1	-0.21	0.24	-10000	0	-0.45	27	27
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.016	0	-10000	0	-10000	0	0
apoptosis	-0.31	0.33	-10000	0	-0.64	27	27
STAT3 (dimer)	0.047	0.007	-10000	0	-10000	0	0
GAB1/CRKL/SHP2/PI3K	-0.016	0.12	-10000	0	-0.92	1	1
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.044	0.055	-10000	0	-0.36	1	1
PTPN11	0.016	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.016	0	-10000	0	-10000	0	0
PTEN	0.002	0.095	-10000	0	-0.69	1	1
ELK1	0.002	0.011	-10000	0	-10000	0	0
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.002	0.012	-10000	0	-10000	0	0
PAK1	0.014	0.05	0.38	1	-10000	0	1
HGF/MET/RANBP10	0.029	0.016	-10000	0	-10000	0	0
HRAS	0.043	0.01	-10000	0	-10000	0	0
DOCK1	0.043	0.055	-10000	0	-0.36	1	1
GAB1	0.029	0.06	-10000	0	-0.41	1	1
CRK	0.036	0.058	-10000	0	-0.38	1	1
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0	0.003	-10000	0	-10000	0	0
JUN	0.002	0.095	-10000	0	-0.69	1	1
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.016	0.012	-10000	0	-10000	0	0
PIK3R1	0.002	0.095	-10000	0	-0.69	1	1
cell morphogenesis	0.063	0.1	-10000	0	-0.68	1	1
GRB2/SHC	0.033	0.011	-10000	0	-10000	0	0
FOS	-0.32	0.35	-10000	0	-0.69	26	26
GLMN	0	0	-10000	0	-10000	0	0
cell motility	0.002	0.011	-10000	0	-10000	0	0
HGF/MET/MUC20	0.018	0.016	-10000	0	-10000	0	0
cell migration	0.032	0.011	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
CBL	0.016	0	-10000	0	-10000	0	0
MET/RANBP10	0.021	0.014	-10000	0	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.041	0.006	-10000	0	-10000	0	0
MET/MUC20	0.01	0.014	-10000	0	-10000	0	0
RAP1B	0.049	0.052	-10000	0	-0.33	1	1
RAP1A	0.029	0.12	-10000	0	-0.43	3	3
HGF/MET/RANBP9	0.029	0.016	-10000	0	-10000	0	0
RAF1	0.048	0.013	-10000	0	-10000	0	0
STAT3	0.047	0.007	-10000	0	-10000	0	0
cell proliferation	0.06	0.01	-10000	0	-10000	0	0
RPS6KB1	0.016	0.005	-10000	0	-10000	0	0
MAPK3	-0.004	0.012	-10000	0	-10000	0	0
MAPK1	-0.004	0.012	-10000	0	-10000	0	0
RANBP9	0.016	0	-10000	0	-10000	0	0
MAPK8	0.056	0.075	-10000	0	-0.35	1	1
SRC	0.048	0.007	-10000	0	-10000	0	0
PI3K	0.019	0.1	-10000	0	-0.72	1	1
MET/Glomulin	0.013	0.012	-10000	0	-10000	0	0
SOS1	0.016	0	-10000	0	-10000	0	0
MAP2K1	0.054	0.012	-10000	0	-10000	0	0
MET	0.013	0.022	-10000	0	-10000	0	0
MAP4K1	0.046	0.055	-10000	0	-0.35	1	1
PTK2	0.016	0	-10000	0	-10000	0	0
MAP2K2	0.054	0.012	-10000	0	-10000	0	0
BAD	0.013	0.051	0.38	1	-10000	0	1
MAP2K4	0.046	0.079	-10000	0	-0.29	1	1
SHP2/GRB2/SOS1/GAB1	-0.005	0.042	-10000	0	-0.31	1	1
INPPL1	0.016	0	-10000	0	-10000	0	0
PXN	0.016	0	-10000	0	-10000	0	0
SH3KBP1	0.016	0	-10000	0	-10000	0	0
HGS	0.024	0.011	-10000	0	-10000	0	0
PLCgamma1/PKC	0.012	0	-10000	0	-10000	0	0
HGF	0.013	0.022	-10000	0	-10000	0	0
RASA1	0.016	0	-10000	0	-10000	0	0
NCK1	0.002	0.095	-10000	0	-0.69	1	1
PTPRJ	0.013	0.022	-10000	0	-10000	0	0
NCK/PLCgamma1	0.028	0.053	-10000	0	-0.35	1	1
PDPK1	-0.002	0.063	0.46	1	-10000	0	1
HGF/MET/SHIP	0.018	0.016	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

Figure S57. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S57. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.001	0.009	-9999	-10000	0	0
HDAC1	0.011	0.001	-9999	-10000	0	0
AES	0.014	0	-9999	-10000	0	0
FBXW11	0.016	0	-9999	-10000	0	0
DTX1	0.016	0	-9999	-10000	0	0
LRP6/FZD1	0.023	0	-9999	-10000	0	0
TLE1	0.002	0.043	-9999	-10000	0	0
AP1	-0.15	0.17	-9999	-0.33	26	26
NCSTN	0.016	0	-9999	-10000	0	0
ADAM10	0.015	0	-9999	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.044	0.014	-9999	-10000	0	0
NICD/RBPSUH	0.037	0.012	-9999	-10000	0	0
WIF1	-0.082	0.24	-9999	-0.69	7	7
NOTCH1	0	0.009	-9999	-10000	0	0
PSENEN	0.007	0.037	-9999	-10000	0	0
KREMEN2	-0.06	0.081	-9999	-10000	0	0
DKK1	-0.033	0.074	-9999	-10000	0	0
beta catenin/beta TrCP1	0.043	0.028	-9999	-10000	0	0
APH1B	0.003	0.095	-9999	-0.69	1	1
APH1A	0.016	0	-9999	-10000	0	0
AXIN1	0.003	0.008	-9999	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.014	0.019	-9999	-10000	0	0
PSEN1	0.016	0	-9999	-10000	0	0
FOS	-0.32	0.35	-9999	-0.69	26	26
JUN	0.002	0.095	-9999	-0.69	1	1
MAP3K7	0.013	0	-9999	-10000	0	0
CTNNB1	0.036	0.029	-9999	-10000	0	0
MAPK3	0.016	0	-9999	-10000	0	0
DKK2/LRP6/Kremen 2	-0.017	0.08	-9999	-0.51	1	1
HNF1A	-0.01	0.058	-9999	-10000	0	0
CTBP1	0.014	0	-9999	-10000	0	0
MYC	0.029	0.003	-9999	-10000	0	0
NKD1	-0.039	0.077	-9999	-10000	0	0
FZD1	0.016	0	-9999	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	0.037	0.012	-9999	-10000	0	0
apoptosis	-0.15	0.17	-9999	-0.32	26	26
Delta 1/NOTCHprecursor	0.037	0.012	-9999	-10000	0	0
DLL1	0.016	0	-9999	-10000	0	0
PPARD	0.029	0.003	-9999	-10000	0	0
Gamma Secretase	0.039	0.055	-9999	-0.36	1	1
APC	0.003	0.008	-9999	-10000	0	0
DVL1	-0.006	0.019	-9999	-10000	0	0
CSNK2A1	0.016	0	-9999	-10000	0	0
MAP3K7IP1	0.013	0	-9999	-10000	0	0
DKK1/LRP6/Kremen 2	-0.034	0.059	-9999	-10000	0	0
LRP6	0.016	0	-9999	-10000	0	0
CSNK1A1	0.016	0	-9999	-10000	0	0
NLK	0.023	0.008	-9999	-10000	0	0
CCND1	0.027	0.017	-9999	-10000	0	0
WNT1	0.016	0	-9999	-10000	0	0
Axin1/APC/beta catenin	0.049	0.026	-9999	-10000	0	0
DKK2	0.002	0.095	-9999	-0.69	1	1
NOTCH1 precursor/DVL1	0.002	0.015	-9999	-10000	0	0
GSK3B	0.015	0	-9999	-10000	0	0
FRAT1	0.015	0	-9999	-10000	0	0
NOTCH/Deltex homolog 1	0.001	0.009	-9999	-10000	0	0
PPP2R5D	0.028	0.047	-9999	-10000	0	0
MAPK1	0.016	0	-9999	-10000	0	0
WNT1/LRP6/FZD1	-0.018	0.14	-9999	-0.39	7	7
RBPJ	0.016	0	-9999	-10000	0	0
CREBBP	0.02	0.001	-9999	-10000	0	0

×

p75(NTR)-mediated signaling

Figure S58. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S58. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.023	0	-9999	-10000	0	0
Necdin/E2F1	-0.24	0.27	-9999	-0.52	26	26
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.037	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/BEX1	0.003	0.035	-9999	-10000	0	0
NT-4/5 (dimer)/p75(NTR)	0.012	0	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
AKT1	0.021	0.1	-9999	-0.74	1	1
IKBKG	0.016	0	-9999	-10000	0	0
BDNF	-0.031	0.11	-9999	-0.69	1	1
MGDIs/NGR/p75(NTR)/LINGO1	0.012	0.04	-9999	-10000	0	0
FURIN	0.016	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	0.005	0.07	-9999	-0.44	1	1
LINGO1	0.003	0.043	-9999	-10000	0	0
Sortilin/TRAF6/NRIF	-0.005	0.041	-9999	-10000	0	0
proBDNF (dimer)	-0.031	0.11	-9999	-0.69	1	1
NTRK1	0.013	0.022	-9999	-10000	0	0
RTN4R	-0.009	0.058	-9999	-10000	0	0
neuron apoptosis	0.039	0.054	-9999	-10000	0	0
IRAK1	0.016	0	-9999	-10000	0	0
SHC1	0.021	0	-9999	-10000	0	0
ARHGDIA	0.016	0	-9999	-10000	0	0
RhoA/GTP	0.012	0	-9999	-10000	0	0
Gamma Secretase	0.038	0.055	-9999	-0.36	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.17	0.21	-9999	-0.4	25	25
MAGEH1	-0.31	0.35	-9999	-0.69	25	25
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.18	0.21	-9999	-0.4	26	26
Mammalian IAPs/DIABLO	-0.005	0.11	-9999	-0.4	4	4
proNGF (dimer)	0	0	-9999	-10000	0	0
MAGED1	0.016	0	-9999	-10000	0	0
APP	0.016	0	-9999	-10000	0	0
NT-4/5 (dimer)	0	0	-9999	-10000	0	0
ZNF274	0.016	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	0.029	0	-9999	-10000	0	0
NGF	0	0	-9999	-10000	0	0
cell cycle arrest	0.011	0.022	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.035	0.006	-9999	-10000	0	0
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.021	0	-9999	-10000	0	0
NCSTN	0.016	0	-9999	-10000	0	0
mol:GTP	0.021	0	-9999	-10000	0	0
PSENEN	0.006	0.037	-9999	-10000	0	0
mol:ceramide	0.028	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.036	0.006	-9999	-10000	0	0
p75(NTR)/beta APP	0.023	0	-9999	-10000	0	0
BEX1	-0.018	0.066	-9999	-10000	0	0
mol:GDP	0.01	0	-9999	-10000	0	0
NGF (dimer)	-0.051	0.15	-9999	-0.4	8	8
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.023	0.036	-9999	-10000	0	0
PIK3R1	0.002	0.095	-9999	-0.69	1	1
RAC1/GTP	0.018	0	-9999	-10000	0	0
MYD88	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	0.021	0	-9999	-10000	0	0
RHOB	0.016	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
MAGE-G1/E2F1	0.012	0.033	-9999	-10000	0	0
NT3 (dimer)	0.013	0.022	-9999	-10000	0	0
TP53	0.029	0.057	-9999	-0.34	1	1
PRDM4	0.029	0	-9999	-10000	0	0
BDNF (dimer)	-0.083	0.18	-9999	-0.46	9	9
PIK3CA	0.002	0.095	-9999	-0.69	1	1
SORT1	0.016	0	-9999	-10000	0	0
activation of caspase activity	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.03	0	-9999	-10000	0	0
RHOC	0.016	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
MAPK10	0.049	0.043	-9999	-10000	0	0
DIABLO	0.016	0	-9999	-10000	0	0
SMPD2	0.029	0	-9999	-10000	0	0
APH1B	0.002	0.095	-9999	-0.69	1	1
APH1A	0.016	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	0.021	0	-9999	-10000	0	0
PSEN1	0.016	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0.023	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	0.021	0.014	-9999	-10000	0	0
MAPK8	0.05	0.043	-9999	-10000	0	0
MAPK9	0.045	0.073	-9999	-0.46	1	1
APAF1	0.016	0	-9999	-10000	0	0
NTF3	0.013	0.022	-9999	-10000	0	0
NTF4	0	0	-9999	-10000	0	0
NDN	-0.32	0.35	-9999	-0.69	26	26
RAC1/GDP	0.012	0	-9999	-10000	0	0
RhoA-B-C/GDP	0	0	-9999	-10000	0	0
p75 CTF/Sortilin/TRAF6/NRIF	0.039	0.011	-9999	-10000	0	0
RhoA-B-C/GTP	0.021	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.036	0.055	-9999	-0.36	1	1
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.016	0.064	-9999	-0.39	1	1
PRKACB	0.016	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.01	0.084	-9999	-0.51	1	1
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.043	0.19	-9999	-0.69	4	4
BIRC2	0.016	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.2	0.18	-9999	-0.45	15	15
BAD	0.054	0.054	-9999	-0.31	1	1
RIPK2	0.013	0.022	-9999	-10000	0	0
NGFR	0.016	0	-9999	-10000	0	0
CYCS	0.035	0	-9999	-10000	0	0
ADAM17	0.013	0.022	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.029	0.011	-9999	-10000	0	0
BCL2L11	0.055	0.054	-9999	-0.31	1	1
BDNF (dimer)/p75(NTR)	-0.008	0.081	-9999	-0.51	1	1
PI3K	0.015	0.11	-9999	-0.78	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.03	0	-9999	-10000	0	0
NDNL2	0.016	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
PRKCI	0.013	0.022	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	0.012	0	-9999	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.03	0	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
PLG	0.01	0.031	-9999	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	0.015	0.055	-9999	-0.34	1	1
SQSTM1	0.016	0	-9999	-10000	0	0
NGFRAP1	0.016	0	-9999	-10000	0	0
CASP3	0.054	0.051	-9999	-0.29	1	1
E2F1	-0.003	0.051	-9999	-10000	0	0
CASP9	0.016	0	-9999	-10000	0	0
IKK complex	0.001	0.005	-9999	-10000	0	0
NGF (dimer)/TRKA	0.01	0.014	-9999	-10000	0	0
MMP7	-0.12	0.25	-9999	-0.69	8	8
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.037	0	-9999	-10000	0	0
MMP3	-0.022	0.11	-9999	-0.69	1	1
APAF-1/Caspase 9	-0.019	0.071	-9999	-10000	0	0

×

EPO signaling pathway

Figure S59. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S59. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.021	0.17	-9999	-10000	0	0
CRKL	0.022	0.051	-9999	-10000	0	0
mol:DAG	0.016	0.071	-9999	-10000	0	0
HRAS	0.042	0.069	-9999	-0.34	1	1
MAPK8	0.026	0.027	-9999	-10000	0	0
RAP1A	0.001	0.11	-9999	-0.4	3	3
GAB1	0.015	0.079	-9999	-0.43	1	1
MAPK14	0.026	0.027	-9999	-10000	0	0
EPO	0.014	0.009	-9999	-10000	0	0
PLCG1	0.016	0.072	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.005	0.038	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.021	0.032	-9999	-10000	0	0
GAB1/SHC/GRB2/SOS1	-0.013	0.051	-9999	-0.37	1	1
EPO/EPOR (dimer)	0.016	0.028	-9999	-10000	0	0
IRS2	-0.22	0.19	-9999	-0.36	34	34
STAT1	-0.006	0.12	-9999	-10000	0	0
STAT5B	0.004	0.099	-9999	-10000	0	0
cell proliferation	0.031	0.028	-9999	-10000	0	0
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.02	0.088	-9999	-0.66	1	1
TEC	0.022	0.051	-9999	-10000	0	0
SOCS3	0.013	0.022	-9999	-10000	0	0
STAT1 (dimer)	-0.006	0.12	-9999	-10000	0	0
JAK2	0.015	0.005	-9999	-10000	0	0
PIK3R1	0.002	0.095	-9999	-0.69	1	1
EPO/EPOR (dimer)/JAK2	0.029	0.062	-9999	-10000	0	0
EPO/EPOR	0.016	0.028	-9999	-10000	0	0
LYN	0.01	0.023	-9999	-10000	0	0
TEC/VAV2	0.031	0.051	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	0.005	0.038	-9999	-10000	0	0
SHC1	0.016	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.026	0.031	-9999	-10000	0	0
mol:IP3	0.016	0.071	-9999	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.2	0.19	-9999	-0.34	34	34
SH2B3	0.015	0.005	-9999	-10000	0	0
NFKB1	0.026	0.027	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	0.003	0.009	-9999	-10000	0	0
PTPN6	0.014	0.053	-9999	-10000	0	0
TEC/VAV2/GRB2	0.038	0.049	-9999	-10000	0	0
EPOR	0.005	0.038	-9999	-10000	0	0
INPP5D	0	0	-9999	-10000	0	0
mol:GDP	-0.014	0.052	-9999	-0.38	1	1
SOS1	0.016	0	-9999	-10000	0	0
PLCG2	-0.011	0.13	-9999	-0.69	2	2
CRKL/CBL/C3G	0.038	0.049	-9999	-10000	0	0
VAV2	0.022	0.051	-9999	-10000	0	0
CBL	0.022	0.051	-9999	-10000	0	0
SHC/Grb2/SOS1	-0.009	0.02	-9999	-10000	0	0
STAT5A	0.004	0.099	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
STAT5 (dimer)	-0.011	0.16	-9999	-10000	0	0
LYN/PLCgamma2	-0.004	0.1	-9999	-0.52	2	2
PTPN11	0.016	0	-9999	-10000	0	0
BTK	0.015	0.07	-9999	-0.33	1	1
BCL2	-0.2	0.44	-9999	-0.87	16	16

×

mTOR signaling pathway

Figure S60. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S60. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0.016	0	-10000	0	-10000	0	0
MKNK1	0.016	0	-10000	0	-10000	0	0
mol:PIP3	-0.041	0.14	0.31	1	-0.36	7	8
FRAP1	0.016	0.036	-10000	0	-10000	0	0
AKT1	-0.006	0.13	0.24	1	-0.3	7	8
INSR	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.021	0	-10000	0	-10000	0	0
mol:GTP	-0.029	0.087	-10000	0	-0.51	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.008	0.027	-10000	0	-10000	0	0
TSC2	0.015	0	-10000	0	-10000	0	0
RHEB/GDP	-0.025	0.076	-10000	0	-0.46	1	1
TSC1	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.023	0.12	-10000	0	-0.37	6	6
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.01	0.031	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.016	0	-10000	0	-10000	0	0
RPS6KB1	0.017	0.072	-10000	0	-0.35	1	1
MAP3K5	-0.004	0.08	-10000	0	-0.41	2	2
PIK3R1	0.003	0.096	-10000	0	-0.69	1	1
apoptosis	-0.004	0.079	-10000	0	-0.41	2	2
mol:LY294002	0	0.001	0.001	1	-0.002	6	7
EIF4B	0.024	0.066	-10000	0	-0.3	1	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.025	0.058	-10000	0	-0.28	1	1
eIF4E/eIF4G1/eIF4A1	-0.002	0.013	-10000	0	-10000	0	0
KIAA1303	0.016	0	-10000	0	-10000	0	0
PI3K	-0.024	0.15	-10000	0	-0.39	7	7
mTOR/RHEB/GTP/Raptor/GBL	0.039	0.054	-10000	0	-0.25	1	1
FKBP1A	0.016	0.001	-10000	0	-10000	0	0
RHEB/GTP	-0.024	0.075	-10000	0	-0.45	1	1
mol:Amino Acids	0	0.001	0.001	1	-0.002	6	7
FKBP12/Rapamycin	0.012	0.002	-10000	0	-10000	0	0
PDPK1	-0.038	0.12	0.25	1	-0.32	7	8
EIF4E	0.016	0	-10000	0	-10000	0	0
ASK1/PP5C	0.005	0.11	-10000	0	-0.56	2	2
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.038	0.008	-10000	0	-10000	0	0
TSC1/TSC2	0.008	0.11	-10000	0	-0.56	1	1
tumor necrosis factor receptor activity	0	0.001	0.002	6	-0.001	1	7
RPS6	0.016	0	-10000	0	-10000	0	0
PPP5C	0.016	0	-10000	0	-10000	0	0
EIF4G1	0.016	0	-10000	0	-10000	0	0
IRS1	-0.035	0.13	-10000	0	-0.4	6	6
INS	0.016	0	-10000	0	-10000	0	0
PTEN	0.002	0.095	-10000	0	-0.69	1	1
PDK2	-0.038	0.12	0.25	1	-0.32	7	8
EIF4EBP1	0.015	0.004	-10000	0	-10000	0	0
PIK3CA	0.003	0.096	-10000	0	-0.69	1	1
PPP2R5D	0.023	0.034	-10000	0	-10000	0	0
peptide biosynthetic process	0.028	0	-10000	0	-10000	0	0
RHEB	0.013	0.022	-10000	0	-10000	0	0
EIF4A1	0.016	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.004	1	-0.004	1	2
EEF2	0.028	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.022	0.003	-10000	0	-10000	0	0

×

IFN-gamma pathway

Figure S61. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S61. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.022	0.073	-9999	-0.34	2	2
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.06	0.066	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.008	0.088	-9999	-0.43	2	2
antigen processing and presentation of peptide antigen via MHC class I	-0.063	0.11	-9999	-0.43	2	2
CaM/Ca2+	-0.009	0.06	-9999	-0.31	2	2
RAP1A	-0.024	0.16	-9999	-0.69	3	3
STAT1 (dimer)/SHP2	0.031	0.071	-9999	-0.31	2	2
AKT1	0.032	0.13	-9999	-0.87	1	1
MAP2K1	0.035	0.086	-9999	-0.33	2	2
MAP3K11	0.033	0.069	-9999	-0.31	2	2
IFNGR1	-0.009	0.13	-9999	-0.69	2	2
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	0.008	0.031	-9999	-10000	0	0
Rap1/GTP	-0.024	0.09	-9999	-0.52	1	1
CRKL/C3G	0.023	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.022	0.076	-9999	-0.35	2	2
CEBPB	0.071	0.086	-9999	-0.35	1	1
STAT3	0.016	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.042	0.067	-9999	-10000	0	0
STAT1	0.03	0.071	-9999	-0.31	2	2
CALM1	0.015	0	-9999	-10000	0	0
IFN-gamma (dimer)	0.007	0.037	-9999	-10000	0	0
PIK3CA	0.002	0.095	-9999	-0.69	1	1
STAT1 (dimer)/PIAS1	0.039	0.067	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	-0.009	0.039	-9999	-10000	0	0
mol:Ca2+	0.02	0.072	-9999	-0.33	2	2
MAPK3	0.049	0.086	-9999	-0.38	1	1
STAT1 (dimer)	-0.087	0.16	-9999	-0.68	2	2
MAPK1	0.049	0.086	-9999	-0.38	1	1
JAK2	0.016	0.007	-9999	-10000	0	0
PIK3R1	0.002	0.095	-9999	-0.69	1	1
JAK1	0.016	0.007	-9999	-10000	0	0
CAMK2D	0.015	0	-9999	-10000	0	0
DAPK1	0.07	0.062	-9999	-10000	0	0
SMAD7	0.018	0.084	-9999	-0.22	1	1
CBL/CRKL/C3G	0.047	0.064	-9999	-10000	0	0
PI3K	-0.022	0.14	-9999	-0.99	1	1
IFNG	0.007	0.037	-9999	-10000	0	0
apoptosis	0.045	0.059	-9999	-10000	0	0
CAMK2G	0.015	0	-9999	-10000	0	0
STAT3 (dimer)	0.016	0	-9999	-10000	0	0
CAMK2A	0.015	0	-9999	-10000	0	0
CAMK2B	0.009	0.031	-9999	-10000	0	0
FRAP1	0.04	0.12	-9999	-0.77	1	1
PRKCD	0.031	0.14	-9999	-0.89	1	1
RAP1B	0.016	0	-9999	-10000	0	0
negative regulation of cell growth	-0.063	0.11	-9999	-0.43	2	2
PTPN2	0.015	0	-9999	-10000	0	0
EP300	0.016	0	-9999	-10000	0	0
IRF1	0.068	0.056	-9999	-10000	0	0
STAT1 (dimer)/PIASy	0.034	0.073	-9999	-0.35	1	1
SOCS1	0.004	0.01	-9999	-10000	0	0
mol:GDP	-0.009	0.051	-9999	-10000	0	0
CASP1	-0.045	0.18	-9999	-0.32	16	16
PTGES2	0.016	0	-9999	-10000	0	0
IRF9	0.061	0.032	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.021	0.13	-9999	-0.93	1	1
RAP1/GDP	-0.025	0.094	-9999	-0.55	1	1
CBL	0.032	0.069	-9999	-0.31	2	2
MAP3K1	0.027	0.09	-9999	-0.34	3	3
PIAS1	0.016	0	-9999	-10000	0	0
PIAS4	0.012	0.022	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.063	0.11	-9999	-0.43	2	2
PTPN11	0.025	0.072	-9999	-0.33	2	2
CREBBP	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0

×

Nectin adhesion pathway

Figure S62. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S62. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	0.017	0.024	-9999	-10000	0	0
PTK2	-0.026	0.088	-9999	-0.43	2	2
positive regulation of JNK cascade	-0.012	0.056	-9999	-0.3	2	2
CDC42/GDP	0.043	0.089	-9999	-0.39	2	2
Rac1/GDP	0.045	0.088	-9999	-0.39	2	2
RAP1B	0.016	0	-9999	-10000	0	0
RAP1A	-0.024	0.16	-9999	-0.69	3	3
CTNNB1	0.016	0	-9999	-10000	0	0
CDC42/GTP	-0.014	0.068	-9999	-0.36	2	2
nectin-3/I-afadin	-0.004	0.1	-9999	-0.51	2	2
RAPGEF1	0.036	0.097	-9999	-0.44	2	2
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.029	0.11	-9999	-0.51	2	2
PDGFB-D/PDGFRB	0.016	0	-9999	-10000	0	0
TLN1	-0.012	0.12	-9999	-0.38	5	5
Rap1/GTP	-0.024	0.076	-9999	-0.31	2	2
IQGAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.006	0.098	-9999	-0.4	3	3
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.004	0.1	-9999	-0.51	2	2
PVR	0.013	0.022	-9999	-10000	0	0
Necl-5(dimer)	0.013	0.022	-9999	-10000	0	0
mol:GDP	0.039	0.1	-9999	-0.48	2	2
MLLT4	0.016	0	-9999	-10000	0	0
PIK3CA	0.002	0.095	-9999	-0.69	1	1
PI3K	0.016	0.13	-9999	-0.49	3	3
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.023	0	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.012	0.058	-9999	-0.31	2	2
PVRL1	0.016	0	-9999	-10000	0	0
PVRL3	-0.023	0.14	-9999	-0.69	2	2
PVRL2	0.016	0	-9999	-10000	0	0
PIK3R1	0.002	0.095	-9999	-0.69	1	1
CDH1	0.002	0.095	-9999	-0.69	1	1
CLDN1	-0.018	0.066	-9999	-10000	0	0
JAM-A/CLDN1	0.001	0.091	-9999	-0.42	2	2
SRC	0.021	0.12	-9999	-0.57	2	2
ITGB3	0.006	0.037	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin	0.023	0	-9999	-10000	0	0
FARP2	0.032	0.1	-9999	-0.48	2	2
RAC1	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.007	0.097	-9999	-0.47	2	2
nectin-1/I-afadin	0.023	0	-9999	-10000	0	0
nectin-2/I-afadin	0.023	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.021	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.008	0.09	-9999	-0.44	2	2
CDC42/GTP/IQGAP1/filamentous actin	0.021	0	-9999	-10000	0	0
F11R	0.013	0.022	-9999	-10000	0	0
positive regulation of filopodium formation	-0.012	0.056	-9999	-0.3	2	2
alphaV/beta3 Integrin/Talin	0.004	0.12	-9999	-0.35	5	5
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.023	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.023	0	-9999	-10000	0	0
PIP5K1C	-0.022	0.13	-9999	-0.41	5	5
VAV2	0.033	0.1	-9999	-0.48	2	2
RAP1/GDP	-0.027	0.086	-9999	-0.36	2	2
ITGAV	0.016	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.008	0.09	-9999	-0.44	2	2
nectin-3(dimer)/I-afadin/I-afadin	-0.004	0.1	-9999	-0.51	2	2
Rac1/GTP	-0.015	0.071	-9999	-0.37	2	2
PTPRM	-0.034	0.14	-9999	-0.4	7	7
E-cadherin/beta catenin/alpha catenin	-0.006	0.046	-9999	-0.34	1	1
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

ceramide signaling pathway

Figure S63. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S63. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.009	0.12	-10000	0	-0.48	1	1
BAG4	0.016	0	-10000	0	-10000	0	0
BAD	0.019	0.044	-10000	0	-10000	0	0
NFKBIA	0.016	0	-10000	0	-10000	0	0
BIRC3	-0.043	0.19	-10000	0	-0.69	4	4
BAX	0.017	0.045	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.006	0.03	-10000	0	-0.11	1	1
IKBKB	0.017	0.12	-10000	0	-0.45	1	1
MAP2K2	0.032	0.042	-10000	0	-10000	0	0
MAP2K1	0.032	0.042	-10000	0	-10000	0	0
SMPD1	0.012	0.03	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.019	0.12	-10000	0	-0.46	1	1
MAP2K4	0.021	0.06	-10000	0	-0.3	1	1
protein ubiquitination	0.018	0.12	-10000	0	-0.46	1	1
EnzymeConsortium:2.7.1.37	0.035	0.046	-10000	0	-10000	0	0
response to UV	0	0.001	-10000	0	-10000	0	0
RAF1	0.026	0.042	-10000	0	-10000	0	0
CRADD	-0.036	0.18	-10000	0	-0.69	4	4
mol:ceramide	0.013	0.043	-10000	0	-0.15	1	1
I-kappa-B-alpha/RELA/p50/ubiquitin	0.021	0	-10000	0	-10000	0	0
MADD	0.016	0	-10000	0	-10000	0	0
MAP3K1	0.014	0.063	-10000	0	-0.33	1	1
TRADD	0.016	0	-10000	0	-10000	0	0
RELA/p50	0.016	0	-10000	0	-10000	0	0
MAPK3	0.035	0.041	-10000	0	-10000	0	0
MAPK1	0.035	0.041	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0.023	0	-10000	0	-10000	0	0
FADD	0.01	0.12	-10000	0	-0.48	1	1
KSR1	0.02	0.042	-10000	0	-10000	0	0
MAPK8	0.028	0.057	-10000	0	-0.28	1	1
TRAF2	0.013	0.022	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.017	0.12	-10000	0	-0.45	1	1
TNF R/SODD	0.013	0.072	-10000	0	-0.51	1	1
TNF	0.007	0.037	-10000	0	-10000	0	0
CYCS	0.051	0.06	0.15	9	-10000	0	9
IKBKG	0.017	0.12	-10000	0	-0.45	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.002	0.12	-10000	0	-0.52	1	1
RELA	0.016	0	-10000	0	-10000	0	0
RIPK1	0.016	0.001	-10000	0	-10000	0	0
AIFM1	0.051	0.059	0.15	8	-10000	0	8
TNF/TNF R/SODD	0.018	0.065	-10000	0	-0.44	1	1
TNFRSF1A	0.003	0.095	-10000	0	-0.69	1	1
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.023	0.031	-10000	0	-10000	0	0
NSMAF	0.011	0.12	-10000	0	-0.48	1	1
response to hydrogen peroxide	0	0.001	-10000	0	-10000	0	0
BCL2	-0.19	0.32	-10000	0	-0.69	16	16

×

RXR and RAR heterodimerization with other nuclear receptor

Figure S64. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S64. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.003	0.012	-9999	-10000	0	0
VDR	-0.011	0.13	-9999	-0.69	2	2
FAM120B	-0.011	0.13	-9999	-0.69	2	2
RXRs/LXRs/DNA/9cRA	0.063	0.052	-9999	-0.3	1	1
RXRs/LXRs/DNA/Oxysterols	0.072	0.05	-9999	-10000	0	0
MED1	0.016	0	-9999	-10000	0	0
mol:9cRA	0.007	0.004	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.037	0.043	-9999	-0.28	1	1
RXRs/NUR77	0.047	0.063	-9999	-0.4	1	1
RXRs/PPAR	-0.18	0.15	-9999	-0.43	2	2
NCOR2	0.016	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.008	0.1	-9999	-0.52	2	2
RARs/VDR/DNA/Vit D3	0.022	0.077	-9999	-0.37	2	2
RARA	0.016	0	-9999	-10000	0	0
NCOA1	0.016	0	-9999	-10000	0	0
VDR/VDR/DNA	-0.011	0.13	-9999	-0.69	2	2
RARs/RARs/DNA/9cRA	0.032	0.002	-9999	-10000	0	0
RARG	0.016	0	-9999	-10000	0	0
RPS6KB1	0.004	0.017	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.037	0.043	-9999	-0.28	1	1
THRA	0.002	0.095	-9999	-0.69	1	1
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.008	0.1	-9999	-0.52	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	0.043	0.064	-9999	-0.41	1	1
NR1H4	0.016	0	-9999	-10000	0	0
RXRs/LXRs/DNA	0.069	0.064	-9999	-0.38	1	1
NR1H2	0.023	0.003	-9999	-10000	0	0
NR1H3	0.023	0.003	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.028	0.096	-9999	-0.36	3	3
NR4A1	0.016	0	-9999	-10000	0	0
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.041	0.039	-9999	-0.24	1	1
RXRG	0.022	0.003	-9999	-10000	0	0
RXR alpha/CCPG	-0.002	0.12	-9999	-0.51	3	3
RXRA	0.009	0.097	-9999	-0.69	1	1
RXRB	0.023	0.003	-9999	-10000	0	0
THRB	0.016	0	-9999	-10000	0	0
PPARG	-0.49	0.32	-9999	-0.69	39	39
PPARD	0.016	0	-9999	-10000	0	0
TNF	0.074	0.056	-9999	-10000	0	0
mol:Oxysterols	0.007	0.003	-9999	-10000	0	0
cholesterol transport	0.072	0.05	-9999	-10000	0	0
PPARA	0.016	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.016	0	-9999	-10000	0	0
RXRs/NUR77/BCL2	-0.062	0.17	-9999	-0.31	16	16
SREBF1	0.076	0.048	-9999	-10000	0	0
RXRs/RXRs/DNA/9cRA	0.044	0.064	-9999	-0.41	1	1
ABCA1	0.077	0.046	-9999	-10000	0	0
RARs/THRs	0.039	0.055	-9999	-0.36	1	1
RXRs/FXR	0.047	0.063	-9999	-0.4	1	1
BCL2	-0.19	0.32	-9999	-0.69	16	16

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

Figure S65. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S65. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.016	0	-10000	0	-10000	0	0
NFATC1	0.042	0.068	-10000	0	-0.3	2	2
NFATC2	0.032	0.042	-10000	0	-10000	0	0
NFATC3	0.018	0	-10000	0	-10000	0	0
YWHAE	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.005	0.11	-10000	0	-0.61	1	1
Exportin 1/Ran/NUP214	0.032	0	-10000	0	-10000	0	0
mol:DAG	0.001	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.009	0.086	-10000	0	-0.51	1	1
BCL2/BAX	-0.14	0.24	-10000	0	-0.52	16	16
CaM/Ca2+/Calcineurin A alpha-beta B1	0.014	0	-10000	0	-10000	0	0
CaM/Ca2+	0.014	0	-10000	0	-10000	0	0
BAX	0.006	0.037	-10000	0	-10000	0	0
MAPK14	0.016	0	-10000	0	-10000	0	0
BAD	0.013	0.022	-10000	0	-10000	0	0
CABIN1/MEF2D	0.014	0.1	-10000	0	-0.58	1	1
Calcineurin A alpha-beta B1/BCL2	-0.19	0.32	-10000	0	-0.69	16	16
FKBP8	0.013	0.022	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.014	0.1	0.57	1	-10000	0	1
KPNB1	0.016	0	-10000	0	-10000	0	0
KPNA2	-0.003	0.051	-10000	0	-10000	0	0
XPO1	0.016	0	-10000	0	-10000	0	0
SFN	-0.012	0.061	-10000	0	-10000	0	0
MAP3K8	-0.036	0.18	-10000	0	-0.69	4	4
NFAT4/CK1 alpha	0.028	0.053	-10000	0	-0.36	1	1
MEF2D/NFAT1/Cbp/p300	0.065	0.037	-10000	0	-10000	0	0
CABIN1	0.005	0.11	-10000	0	-0.62	1	1
CALM1	0.016	0	-10000	0	-10000	0	0
RAN	0.016	0	-10000	0	-10000	0	0
MAP3K1	0.002	0.095	-10000	0	-0.69	1	1
CAMK4	0.01	0.031	-10000	0	-10000	0	0
mol:Ca2+	0.001	0	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
YWHAH	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.023	0.002	-10000	0	-10000	0	0
YWHAB	0.016	0	-10000	0	-10000	0	0
MAPK8	0.016	0	-10000	0	-10000	0	0
MAPK9	0.002	0.095	-10000	0	-0.69	1	1
YWHAG	0.016	0	-10000	0	-10000	0	0
FKBP1A	0.016	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.061	0.058	-10000	0	-10000	0	0
PRKCH	-0.037	0.18	-10000	0	-0.69	4	4
CABIN1/Cbp/p300	0.025	0	-10000	0	-10000	0	0
CASP3	0.016	0	-10000	0	-10000	0	0
PIM1	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.011	0	-10000	0	-10000	0	0
apoptosis	-0.047	0.075	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.044	0.011	-10000	0	-10000	0	0
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.016	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.018	0.057	-10000	0	-0.4	1	1
BAD/BCL-XL	0.021	0.014	-10000	0	-10000	0	0
PRKCD	0.016	0	-10000	0	-10000	0	0
NUP214	0.016	0	-10000	0	-10000	0	0
PRKCZ	0.001	0	-10000	0	-10000	0	0
PRKCA	0.016	0	-10000	0	-10000	0	0
PRKCG	0.016	0	-10000	0	-10000	0	0
PRKCQ	-0.033	0.074	-10000	0	-10000	0	0
FKBP38/BCL2	-0.14	0.24	-10000	0	-0.51	16	16
EP300	0.016	0	-10000	0	-10000	0	0
PRKCB1	-0.011	0.13	-10000	0	-0.69	2	2
CSNK2A1	0.016	0	-10000	0	-10000	0	0
NFATc/JNK1	0.05	0.065	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0.021	0.012	-10000	0	-10000	0	0
FKBP12/FK506	0.012	0	-10000	0	-10000	0	0
CSNK1A1	0.023	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.02	0.017	-10000	0	-10000	0	0
NFATc/ERK1	0.049	0.065	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.02	0.081	-10000	0	-0.51	1	1
NR4A1	0.067	0.033	-10000	0	-10000	0	0
GSK3B	0.016	0	-10000	0	-10000	0	0
positive T cell selection	0.018	0	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.007	0.023	-10000	0	-10000	0	0
RCH1/ KPNB1	0.012	0.033	-10000	0	-10000	0	0
YWHAQ	0.016	0	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
AKAP5	0.015	0.003	-10000	0	-10000	0	0
MEF2D	0.016	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.016	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.05	0.065	-10000	0	-10000	0	0
CREBBP	0.016	0	-10000	0	-10000	0	0
BCL2	-0.19	0.32	-10000	0	-0.69	16	16

×

Syndecan-3-mediated signaling events

Figure S66. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S66. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.016	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.12	0.18	-9999	-0.33	23	23
Syndecan-3/Neurocan	0.026	0.014	-9999	-10000	0	0
POMC	0.013	0.022	-9999	-10000	0	0
EGFR	-0.066	0.22	-9999	-0.69	6	6
Syndecan-3/EGFR	-0.019	0.12	-9999	-0.37	6	6
AGRP	0.016	0	-9999	-10000	0	0
NCSTN	0.016	0	-9999	-10000	0	0
PSENEN	0.006	0.037	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.002	0.095	-9999	-0.69	1	1
APH1A	0.016	0	-9999	-10000	0	0
NCAN	0.016	0	-9999	-10000	0	0
long-term memory	0.034	0.013	-9999	-10000	0	0
Syndecan-3/IL8	0.004	0.037	-9999	-10000	0	0
PSEN1	0.016	0	-9999	-10000	0	0
Src/Cortactin	0.023	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
limb bud formation	-0.002	0.01	-9999	-10000	0	0
MC4R	0.013	0.022	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PTN	-0.28	0.35	-9999	-0.69	23	23
FGFR/FGF/Syndecan-3	-0.002	0.01	-9999	-10000	0	0
neuron projection morphogenesis	-0.11	0.18	-9999	-0.39	1	1
Syndecan-3/AgRP	0.026	0.014	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	0.034	0.015	-9999	-10000	0	0
Fyn/Cortactin	0.023	0	-9999	-10000	0	0
SDC3	-0.002	0.01	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	0.004	0.037	-9999	-10000	0	0
IL8	-0.036	0.076	-9999	-10000	0	0
Syndecan-3/Fyn/Cortactin	0.035	0.013	-9999	-10000	0	0
Syndecan-3/CASK	-0.001	0.01	-9999	-10000	0	0
alpha-MSH/MC4R	0.019	0.02	-9999	-10000	0	0
Gamma Secretase	0.038	0.055	-9999	-0.36	1	1

×

Signaling mediated by p38-alpha and p38-beta

Figure S67. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S67. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	0.013	0.16	-9999	-1.1	1	1
MKNK1	0.016	0	-9999	-10000	0	0
MAPK14	0.016	0.046	-9999	-0.28	1	1
ATF2/c-Jun	0.023	0.12	-9999	-0.78	1	1
MAPK11	0.016	0.046	-9999	-0.28	1	1
MITF	0.031	0.054	-9999	-0.33	1	1
MAPKAPK5	0.031	0.054	-9999	-0.33	1	1
KRT8	0.028	0.057	-9999	-0.33	1	1
MAPKAPK3	0.016	0	-9999	-10000	0	0
MAPKAPK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/CK2	0.022	0.067	-9999	-0.42	1	1
CEBPB	0.031	0.054	-9999	-0.33	1	1
SLC9A1	0.031	0.054	-9999	-0.33	1	1
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.035	0.06	-9999	-0.32	1	1
p38alpha-beta/MNK1	0.032	0.054	-9999	-0.33	1	1
JUN	0.023	0.12	-9999	-0.78	1	1
PPARGC1A	0.03	0.062	-9999	-0.39	1	1
USF1	0.02	0.058	-9999	-0.33	1	1
RAB5/GDP/GDI1	-0.005	0.032	-9999	-10000	0	0
NOS2	0.021	0.054	-9999	-0.34	1	1
DDIT3	0.03	0.057	-9999	-0.33	1	1
RAB5A	0.016	0	-9999	-10000	0	0
HSPB1	0.027	0.05	-9999	-10000	0	0
p38alpha-beta/HBP1	0.004	0.13	-9999	-0.43	4	4
CREB1	0.02	0.1	-9999	-0.62	1	1
RAB5/GDP	0.012	0	-9999	-10000	0	0
EIF4E	0.036	0.047	-9999	-10000	0	0
RPS6KA4	0.031	0.054	-9999	-0.33	1	1
PLA2G4A	0.002	0.13	-9999	-0.52	3	3
GDI1	0.03	0.056	-9999	-0.33	1	1
TP53	0.031	0.066	-9999	-0.41	1	1
RPS6KA5	-0.001	0.15	-9999	-0.49	4	4
ESR1	-0.021	0.14	-9999	-0.37	7	7
HBP1	-0.024	0.16	-9999	-0.69	3	3
MEF2C	-0.076	0.2	-9999	-0.4	14	14
MEF2A	0.031	0.054	-9999	-0.33	1	1
EIF4EBP1	0.019	0.1	-9999	-0.62	1	1
KRT19	0.001	0.12	-9999	-0.35	5	5
ELK4	0.031	0.054	-9999	-0.33	1	1
ATF6	0.031	0.054	-9999	-0.33	1	1
ATF1	0.02	0.1	-9999	-0.62	1	1
p38alpha-beta/MAPKAPK2	0.032	0.054	-9999	-0.33	1	1
p38alpha-beta/MAPKAPK3	0.032	0.054	-9999	-0.33	1	1

×

TCR signaling in naïve CD8+ T cells

Figure S68. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S68. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.014	0.054	-9999	-10000	0	0
FYN	0.024	0.12	-9999	-0.46	1	1
LAT/GRAP2/SLP76	-0.03	0.091	-9999	-0.45	2	2
IKBKB	0.016	0	-9999	-10000	0	0
AKT1	0.036	0.098	-9999	-0.29	2	2
B2M	-0.009	0.13	-9999	-0.69	2	2
IKBKG	-0.005	0.02	-9999	-10000	0	0
MAP3K8	-0.037	0.18	-9999	-0.69	4	4
mol:Ca2+	0	0.006	-9999	-10000	0	0
integrin-mediated signaling pathway	-0.005	0.11	-9999	-0.44	3	3
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.032	0.12	-9999	-0.35	4	4
TRPV6	0.002	0.004	-9999	-10000	0	0
CD28	-0.076	0.24	-9999	-0.69	7	7
SHC1	0.032	0.089	-9999	-0.3	1	1
receptor internalization	0.026	0.088	-9999	-0.25	3	3
PRF1	0.036	0.063	-9999	-10000	0	0
KRAS	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
COT/AKT1	0.017	0.11	-9999	-0.27	5	5
LAT	0.032	0.089	-9999	-0.3	1	1
EntrezGene:6955	0.001	0.002	-9999	-10000	0	0
CD3D	0.017	0.002	-9999	-10000	0	0
CD3E	0.017	0.002	-9999	-10000	0	0
CD3G	0.014	0.022	-9999	-10000	0	0
RASGRP2	0.011	0.029	-9999	-0.18	1	1
RASGRP1	0.041	0.097	-9999	-0.34	1	1
HLA-A	0.011	0.031	-9999	-10000	0	0
RASSF5	0.016	0	-9999	-10000	0	0
RAP1A/GTP/RAPL	-0.005	0.11	-9999	-0.44	3	3
mol:GTP	0	0	-9999	-10000	0	0
mol:GDP	0.036	0.039	-9999	-0.094	2	2
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.012	0.033	-9999	-10000	0	0
PRKCA	-0.016	0.048	-9999	-0.21	2	2
GRAP2	0.015	0	-9999	-10000	0	0
mol:IP3	-0.026	0.075	-9999	-0.31	3	3
EntrezGene:6957	0.002	0.002	-9999	-10000	0	0
TCR/CD3/MHC I/CD8	0.024	0.067	-9999	-0.2	2	2
ORAI1	0.002	0.005	-9999	-10000	0	0
CSK	0.031	0.087	-9999	-0.3	1	1
B7 family/CD28	-0.008	0.19	-9999	-0.46	6	6
CHUK	0.016	0	-9999	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.025	0.095	-9999	-0.33	1	1
PTPN6	0.026	0.094	-9999	-0.32	2	2
VAV1	0.026	0.11	-9999	-0.47	1	1
Monovalent TCR/CD3	0.015	0.072	-9999	-0.28	3	3
CBL	0.016	0	-9999	-10000	0	0
LCK	0.022	0.11	-9999	-0.46	1	1
PAG1	0.024	0.096	-9999	-0.3	1	1
RAP1A	-0.024	0.16	-9999	-0.69	3	3
TCR/CD3/MHC I/CD8/LCK	0.021	0.1	-9999	-0.34	2	2
CD80	0.016	0.002	-9999	-10000	0	0
CD86	-0.011	0.13	-9999	-0.69	2	2
PDK1/CARD11/BCL10/MALT1	-0.013	0.041	-9999	-0.2	1	1
HRAS	0.016	0	-9999	-10000	0	0
GO:0035030	-0.004	0.16	-9999	-0.4	6	6
CD8A	0.002	0.002	-9999	-10000	0	0
CD8B	0.008	0.037	-9999	-10000	0	0
PTPRC	-0.036	0.19	-9999	-0.69	4	4
PDK1/PKC theta	0.037	0.11	-9999	-0.34	2	2
CSK/PAG1	0.03	0.093	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
peptide-MHC class I	0.002	0.1	-9999	-0.52	2	2
GRAP2/SLP76	-0.031	0.1	-9999	-0.49	2	2
STIM1	0.002	0.004	-9999	-10000	0	0
RAS family/GTP	0.046	0.046	-9999	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.026	0.09	-9999	-0.26	3	3
mol:DAG	-0.024	0.068	-9999	-0.28	3	3
RAP1A/GDP	0.01	0.041	-9999	-0.14	3	3
PLCG1	0.015	0	-9999	-10000	0	0
CD247	-0.022	0.16	-9999	-0.69	3	3
cytotoxic T cell degranulation	0.036	0.063	-9999	-10000	0	0
RAP1A/GTP	-0.008	0.028	-9999	-0.1	4	4
mol:PI-3-4-5-P3	0.033	0.11	-9999	-0.3	4	4
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.032	0.092	-9999	-0.38	3	3
NRAS	0.013	0.022	-9999	-10000	0	0
ZAP70	0.01	0.031	-9999	-10000	0	0
GRB2/SOS1	0.023	0	-9999	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.032	0.095	-9999	-0.39	3	3
MALT1	0.013	0.022	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
CD8 heterodimer	0.008	0.024	-9999	-10000	0	0
CARD11	0.01	0.031	-9999	-10000	0	0
PRKCB	-0.017	0.049	-9999	-0.2	3	3
PRKCE	-0.016	0.048	-9999	-0.21	2	2
PRKCQ	0.03	0.12	-9999	-0.39	2	2
LCP2	-0.011	0.13	-9999	-0.69	2	2
BCL10	0.016	0	-9999	-10000	0	0
regulation of survival gene product expression	0.036	0.088	-9999	-0.25	2	2
IKK complex	0.043	0.038	-9999	-10000	0	0
RAS family/GDP	-0.001	0.004	-9999	-10000	0	0
MAP3K14	0.024	0.092	-9999	-0.24	2	2
PDPK1	0.038	0.095	-9999	-0.33	1	1
TCR/CD3/MHC I/CD8/Fyn	0.024	0.1	-9999	-0.42	2	2

×

HIV-1 Nef: Negative effector of Fas and TNF-alpha

Figure S69. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S69. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.016	0	-9999	-10000	0	0
Caspase 8 (4 units)	0.001	0.12	-9999	-0.6	1	1
NEF	0.006	0.001	-9999	-10000	0	0
NFKBIA	0.009	0.032	-9999	-10000	0	0
BIRC3	-0.011	0.2	-9999	-0.7	4	4
CYCS	0.015	0.096	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
CD247	-0.018	0.16	-9999	-0.68	3	3
MAP2K7	0.018	0.091	-9999	-10000	0	0
protein ubiquitination	0.044	0.083	-9999	-10000	0	0
CRADD	-0.037	0.18	-9999	-0.69	4	4
DAXX	0.016	0	-9999	-10000	0	0
FAS	-0.05	0.2	-9999	-0.69	5	5
BID	0.007	0.1	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	0.015	0.093	-9999	-0.31	4	4
TRADD	0.016	0	-9999	-10000	0	0
MAP3K5	-0.011	0.13	-9999	-0.69	2	2
CFLAR	0.002	0.095	-9999	-0.69	1	1
FADD	0.016	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.015	0.093	-9999	-0.31	4	4
MAPK8	0.025	0.087	-9999	-10000	0	0
APAF1	0.016	0	-9999	-10000	0	0
TRAF1	0.016	0	-9999	-10000	0	0
TRAF2	0.013	0.022	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.001	0.1	-9999	-0.26	7	7
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.03	0.099	-9999	-10000	0	0
CHUK	0.044	0.087	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.006	0.14	-9999	-0.36	7	7
TCRz/NEF	-0.006	0.12	-9999	-0.51	3	3
TNF	0.006	0.037	-9999	-10000	0	0
FASLG	0.007	0.1	-9999	-0.42	3	3
NFKB1	0.009	0.032	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.018	0.065	-9999	-0.44	1	1
CASP6	-0.033	0.1	-9999	-0.6	1	1
CASP7	0.015	0.19	-9999	-0.54	5	5
RELA	0.009	0.032	-9999	-10000	0	0
CASP2	0.016	0	-9999	-10000	0	0
CASP3	0.015	0.19	-9999	-0.54	5	5
TNFRSF1A	0.002	0.095	-9999	-0.69	1	1
TNFR1A/BAG4	0.013	0.072	-9999	-0.51	1	1
CASP8	0.016	0	-9999	-10000	0	0
CASP9	0.016	0	-9999	-10000	0	0
MAP3K14	0.037	0.094	-9999	-10000	0	0
APAF-1/Caspase 9	-0.048	0.13	-9999	-0.48	4	4
BCL2	-0.073	0.19	-9999	-0.44	6	6

×

EPHB forward signaling

Figure S70. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S70. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.013	0.025	-10000	0	-10000	0	0
cell-cell adhesion	0.031	0.089	-10000	0	-10000	0	0
Ephrin B/EPHB2/RasGAP	0.038	0.055	-10000	0	-0.36	1	1
ITSN1	0.016	0	-10000	0	-10000	0	0
PIK3CA	0.002	0.095	-10000	0	-0.69	1	1
SHC1	0.016	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.001	0.089	-10000	0	-0.44	2	2
Ephrin B1/EPHB1	-0.031	0.15	-10000	0	-0.44	6	6
HRAS/GDP	-0.031	0.087	-10000	0	-10000	0	0
Ephrin B/EPHB1/GRB7	0.001	0.13	-10000	0	-0.36	6	6
Endophilin/SYNJ1	0.028	0.054	-10000	0	-0.34	1	1
KRAS	0.016	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.001	0.13	-10000	0	-0.36	6	6
endothelial cell migration	-0.014	0.099	-10000	0	-0.73	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
GRB7	0.01	0.031	-10000	0	-10000	0	0
PAK1	0.037	0.055	-10000	0	-0.34	1	1
HRAS	0.016	0	-10000	0	-10000	0	0
RRAS	0.029	0.055	-10000	0	-0.34	1	1
DNM1	0.002	0.095	-10000	0	-0.69	1	1
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.001	0.12	-10000	0	-0.34	6	6
lamellipodium assembly	-0.031	0.089	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.012	0.097	-10000	0	-0.27	5	5
PIK3R1	0.002	0.095	-10000	0	-0.69	1	1
EPHB2	0	0.047	-10000	0	-10000	0	0
EPHB3	-0.007	0.1	-10000	0	-0.69	1	1
EPHB1	-0.05	0.2	-10000	0	-0.69	5	5
EPHB4	0.016	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.095	-10000	0	-10000	0	0
Ephrin B/EPHB2	0.023	0.058	-10000	0	-0.37	1	1
Ephrin B/EPHB3	0.018	0.078	-10000	0	-0.37	2	2
JNK cascade	-0.016	0.13	-10000	0	-0.36	7	7
Ephrin B/EPHB1	-0.008	0.13	-10000	0	-0.37	6	6
RAP1/GDP	0.014	0.11	-10000	0	-10000	0	0
EFNB2	0.016	0	-10000	0	-10000	0	0
EFNB3	0.016	0	-10000	0	-10000	0	0
EFNB1	0.002	0.095	-10000	0	-0.69	1	1
Ephrin B2/EPHB1-2	-0.017	0.12	-10000	0	-0.4	5	5
RAP1B	0.016	0	-10000	0	-10000	0	0
RAP1A	-0.024	0.16	-10000	0	-0.69	3	3
CDC42/GTP	-0.031	0.093	-10000	0	-10000	0	0
Rap1/GTP	-0.046	0.1	-10000	0	-10000	0	0
axon guidance	0.013	0.025	-10000	0	-10000	0	0
MAPK3	0.027	0.088	-10000	0	-10000	0	0
MAPK1	0.027	0.088	-10000	0	-10000	0	0
Rac1/GDP	0.028	0.09	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.024	0.067	-10000	0	-10000	0	0
CDC42/GDP	0.028	0.09	-10000	0	-10000	0	0
PI3K	0.022	0.1	-10000	0	-0.74	1	1
EFNA5	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.021	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.033	0.044	-10000	0	-0.28	1	1
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	-0.029	0.087	-10000	0	-10000	0	0
PTK2	0.013	0.03	-10000	0	-10000	0	0
MAP4K4	-0.016	0.14	-10000	0	-0.36	7	7
SRC	0.016	0	-10000	0	-10000	0	0
KALRN	0.016	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0.023	0.002	-10000	0	-10000	0	0
neuron projection morphogenesis	0.043	0.094	-10000	0	-10000	0	0
MAP2K1	0.02	0.092	-10000	0	-10000	0	0
WASL	0.015	0.002	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.023	0.14	-10000	0	-0.39	7	7
cell migration	0.025	0.1	-10000	0	-10000	0	0
NRAS	0.013	0.022	-10000	0	-10000	0	0
SYNJ1	0.029	0.055	-10000	0	-0.34	1	1
PXN	0.016	0	-10000	0	-10000	0	0
TF	0.022	0.087	-10000	0	-0.33	3	3
HRAS/GTP	-0.032	0.097	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2	-0.025	0.13	-10000	0	-0.4	6	6
cell adhesion mediated by integrin	-0.001	0.06	0.37	1	-10000	0	1
RAC1	0.016	0	-10000	0	-10000	0	0
mol:GTP	0.001	0.12	-10000	0	-0.33	6	6
RAC1-CDC42/GTP	-0.037	0.097	-10000	0	-0.33	1	1
RASA1	0.016	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.033	0.087	-10000	0	-10000	0	0
ruffle organization	0.024	0.11	-10000	0	-10000	0	0
NCK1	0.002	0.095	-10000	0	-0.69	1	1
receptor internalization	0.029	0.072	-10000	0	-0.33	2	2
Ephrin B/EPHB2/KALRN	0.038	0.055	-10000	0	-0.36	1	1
ROCK1	0.009	0.081	-10000	0	-0.4	2	2
RAS family/GDP	-0.02	0.057	-10000	0	-10000	0	0
Rac1/GTP	-0.032	0.094	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/Paxillin	0.007	0.1	-10000	0	-0.28	6	6

×

Calcium signaling in the CD4+ TCR pathway

Figure S71. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S71. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.018	0.087	-9999	-0.42	2	2
NFATC2	0.035	0.01	-9999	-10000	0	0
NFATC3	0.035	0.01	-9999	-10000	0	0
CD40LG	-0.035	0.19	-9999	-0.47	2	2
PTGS2	-0.044	0.21	-9999	-0.56	3	3
JUNB	0.016	0	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.002	0.005	-9999	-10000	0	0
CaM/Ca2+	0.002	0.005	-9999	-10000	0	0
CALM1	0.019	0.003	-9999	-10000	0	0
JUN	0.007	0.094	-9999	-0.68	1	1
mol:Ca2+	0.002	0.004	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.007	0.006	-9999	-10000	0	0
FOSL1	0.013	0.022	-9999	-10000	0	0
CREM	0.015	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.008	0.067	-9999	-10000	0	0
FOS	-0.32	0.35	-9999	-0.68	26	26
IFNG	-0.037	0.19	-9999	-0.46	3	3
AP-1/NFAT1-c-4	-0.041	0.22	-9999	-0.51	3	3
FASLG	-0.035	0.19	-9999	-0.47	2	2
NFAT1-c-4/ICER1	-0.006	0.061	-9999	-0.33	1	1
IL2RA	-0.035	0.19	-9999	-0.47	2	2
FKBP12/FK506	0.012	0	-9999	-10000	0	0
CSF2	-0.035	0.19	-9999	-0.47	2	2
JunB/Fra1/NFAT1-c-4	0.027	0.07	-9999	-10000	0	0
IL4	-0.035	0.19	-9999	-0.47	2	2
IL2	-0.002	0.008	-9999	-10000	0	0
IL3	0.004	0.008	-9999	-10000	0	0
FKBP1A	0.016	0	-9999	-10000	0	0
BATF3	0	0	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.024	0	-9999	-10000	0	0

×

LPA receptor mediated events

Figure S72. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S72. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.027	0.01	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.051	0.015	-9999	-10000	0	0
AP1	-0.18	0.18	-9999	-0.35	27	27
mol:PIP3	-0.047	0.15	-9999	-0.42	6	6
AKT1	0.05	0.043	-9999	-10000	0	0
PTK2B	0.021	0.009	-9999	-10000	0	0
RHOA	0.026	0.006	-9999	-10000	0	0
PIK3CB	0.015	0	-9999	-10000	0	0
mol:Ca2+	0.027	0.021	-9999	-10000	0	0
MAGI3	0.015	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
apoptosis	0.017	0.009	-9999	-10000	0	0
HRAS/GDP	0.012	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.021	0.072	-9999	-0.34	2	2
NF kappa B1 p50/RelA	-0.001	0.007	-9999	-10000	0	0
endothelial cell migration	0.019	0.021	-9999	-10000	0	0
ADCY4	0.012	0.091	-9999	-0.48	1	1
ADCY5	0.023	0.08	-9999	-0.48	1	1
ADCY6	0.023	0.08	-9999	-0.48	1	1
ADCY7	0.023	0.08	-9999	-0.48	1	1
ADCY1	0.023	0.08	-9999	-0.48	1	1
ADCY2	0.023	0.08	-9999	-0.48	1	1
ADCY3	0.023	0.08	-9999	-0.48	1	1
ADCY8	0.023	0.08	-9999	-0.48	1	1
ADCY9	0.023	0.08	-9999	-0.48	1	1
GSK3B	0.028	0.008	-9999	-10000	0	0
arachidonic acid secretion	0.03	0.073	-9999	-0.42	1	1
GNG2	0.015	0	-9999	-10000	0	0
TRIP6	0.023	0.002	-9999	-10000	0	0
GNAO1	0.02	0.011	-9999	-10000	0	0
HRAS	0.016	0	-9999	-10000	0	0
NFKBIA	0.038	0.017	-9999	-10000	0	0
GAB1	0.002	0.095	-9999	-0.69	1	1
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0.03	0	-9999	-10000	0	0
JUN	0.002	0.095	-9999	-0.69	1	1
LPA/LPA2/NHERF2	0.006	0.017	-9999	-10000	0	0
TIAM1	0.001	0.004	-9999	-10000	0	0
PIK3R1	0.002	0.095	-9999	-0.69	1	1
mol:IP3	0.027	0.021	-9999	-10000	0	0
PLCB3	0.02	0.015	-9999	-10000	0	0
FOS	-0.32	0.35	-9999	-0.69	26	26
positive regulation of mitosis	0.03	0.073	-9999	-0.42	1	1
LPA/LPA1-2-3	-0.001	0.008	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.016	0	-9999	-10000	0	0
stress fiber formation	0.028	0.008	-9999	-10000	0	0
GNAZ	0.02	0.011	-9999	-10000	0	0
EGFR/PI3K-beta/Gab1	-0.05	0.16	-9999	-0.45	6	6
positive regulation of dendritic cell cytokine production	-0.001	0.008	-9999	-10000	0	0
LPA/LPA2/MAGI-3	0.01	0.007	-9999	-10000	0	0
ARHGEF1	0.034	0.009	-9999	-10000	0	0
GNAI2	0.02	0.011	-9999	-10000	0	0
GNAI3	0.012	0.063	-9999	-0.44	1	1
GNAI1	-0.006	0.11	-9999	-0.44	3	3
LPA/LPA3	-0.001	0.005	-9999	-10000	0	0
LPA/LPA2	-0.001	0.005	-9999	-10000	0	0
LPA/LPA1	-0.002	0.012	-9999	-10000	0	0
HB-EGF/EGFR	-0.065	0.19	-9999	-0.5	8	8
HBEGF	-0.026	0.13	-9999	-0.51	3	3
mol:DAG	0.027	0.021	-9999	-10000	0	0
cAMP biosynthetic process	0.028	0.081	-9999	-0.48	1	1
NFKB1	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
GNB1	0.015	0	-9999	-10000	0	0
LYN	0.038	0.018	-9999	-10000	0	0
GNAQ	0.003	0.004	-9999	-10000	0	0
LPAR2	0	0	-9999	-10000	0	0
LPAR3	0	0	-9999	-10000	0	0
LPAR1	0.004	0.008	-9999	-10000	0	0
IL8	-0.11	0.14	-9999	-0.42	7	7
PTK2	0.018	0.009	-9999	-10000	0	0
Rac1/GDP	0.012	0	-9999	-10000	0	0
CASP3	0.017	0.009	-9999	-10000	0	0
EGFR	-0.066	0.22	-9999	-0.69	6	6
PLCG1	0.015	0.02	-9999	-0.13	1	1
PLD2	0.018	0.009	-9999	-10000	0	0
G12/G13	0.028	0.01	-9999	-10000	0	0
PI3K-beta	-0.005	0.04	-9999	-0.3	1	1
cell migration	0.003	0.01	-9999	-10000	0	0
SLC9A3R2	0.009	0.031	-9999	-10000	0	0
PXN	0.028	0.008	-9999	-10000	0	0
HRAS/GTP	0.03	0.074	-9999	-0.44	1	1
RAC1	0.016	0	-9999	-10000	0	0
MMP9	-0.018	0.066	-9999	-10000	0	0
PRKCE	0.016	0	-9999	-10000	0	0
PRKCD	0.034	0.02	-9999	-10000	0	0
Gi(beta/gamma)	0.028	0.078	-9999	-0.46	1	1
mol:LPA	0.004	0.008	-9999	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	0.002	0.009	-9999	-10000	0	0
MAPKKK cascade	0.03	0.073	-9999	-0.42	1	1
contractile ring contraction involved in cytokinesis	0.026	0.006	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	0.005	0.052	-9999	-0.37	1	1
GNA15	0.012	0.004	-9999	-10000	0	0
GNA12	0.015	0	-9999	-10000	0	0
GNA13	0.015	0	-9999	-10000	0	0
MAPT	0.021	0.074	-9999	-0.35	2	2
GNA11	0.012	0.004	-9999	-10000	0	0
Rac1/GTP	0.031	0.001	-9999	-10000	0	0
MMP2	0.019	0.021	-9999	-10000	0	0

×

IL6-mediated signaling events

Figure S73. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S73. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.082	0.15	-9999	-10000	0	0
CRP	0.082	0.15	-9999	-10000	0	0
cell cycle arrest	0.091	0.15	-9999	-0.5	1	1
TIMP1	0.067	0.15	-9999	-10000	0	0
IL6ST	0.014	0.095	-9999	-0.67	1	1
Rac1/GDP	0.01	0.15	-9999	-0.5	1	1
AP1	-0.091	0.2	-9999	-0.35	9	9
GAB2	0.021	0.009	-9999	-10000	0	0
TNFSF11	0.075	0.16	-9999	-10000	0	0
HSP90B1	0.054	0.044	-9999	-10000	0	0
GAB1	0.006	0.096	-9999	-0.69	1	1
MAPK14	-0.021	0.13	-9999	-10000	0	0
AKT1	0.058	0.12	-9999	-0.78	1	1
FOXO1	0.063	0.11	-9999	-0.73	1	1
MAP2K6	-0.022	0.14	-9999	-10000	0	0
mol:GTP	0.001	0.001	-9999	-10000	0	0
MAP2K4	0.046	0.15	-9999	-0.42	1	1
MITF	-0.003	0.14	-9999	-0.3	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.016	0	-9999	-10000	0	0
A2M	-0.22	0.51	-9999	-1.3	10	10
CEBPB	0.026	0.001	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.051	0.098	-9999	-0.33	1	1
STAT3	0.091	0.16	-9999	-0.52	1	1
STAT1	0.001	0.019	-9999	-10000	0	0
CEBPD	0.044	0.27	-9999	-0.96	3	3
PIK3CA	0.004	0.095	-9999	-0.69	1	1
PI3K	0.008	0.13	-9999	-0.94	1	1
JUN	0.003	0.095	-9999	-0.69	1	1
PIAS3/MITF	0.003	0.13	-9999	-10000	0	0
MAPK11	-0.021	0.13	-9999	-10000	0	0
STAT3 (dimer)/FOXO1	0.068	0.21	-9999	-0.52	2	2
GRB2/SOS1/GAB family	-0.04	0.12	-9999	-0.53	1	1
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.03	0.15	-9999	-10000	0	0
GRB2	0.019	0.006	-9999	-10000	0	0
JAK2	0.016	0	-9999	-10000	0	0
LBP	0.078	0.14	-9999	-10000	0	0
PIK3R1	0.004	0.095	-9999	-0.69	1	1
JAK1	0.021	0.003	-9999	-10000	0	0
MYC	0.082	0.15	-9999	-10000	0	0
FGG	0.082	0.15	-9999	-10000	0	0
macrophage differentiation	0.091	0.15	-9999	-0.5	1	1
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.1	0.16	-9999	-0.33	18	18
JUNB	0.078	0.15	-9999	-10000	0	0
FOS	-0.32	0.35	-9999	-0.69	26	26
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.013	0.15	-9999	-0.33	1	1
STAT1/PIAS1	0.013	0.14	-9999	-0.34	1	1
GRB2/SOS1/GAB family/SHP2/PI3K	0.047	0.12	-9999	-0.84	1	1
STAT3 (dimer)	0.091	0.16	-9999	-0.51	1	1
PRKCD	0.077	0.15	-9999	-10000	0	0
IL6R	0.021	0.003	-9999	-10000	0	0
SOCS3	-0.027	0.13	-9999	-10000	0	0
gp130 (dimer)/JAK1/JAK1/LMO4	0.052	0.064	-9999	-0.4	1	1
Rac1/GTP	0.02	0.15	-9999	-0.4	2	2
HCK	0.003	0.095	-9999	-0.69	1	1
MAPKKK cascade	0.066	0.11	-9999	-0.54	1	1
bone resorption	0.075	0.15	-9999	-10000	0	0
IRF1	0.082	0.15	-9999	-10000	0	0
mol:GDP	-0.005	0.16	-9999	-0.42	2	2
SOS1	0.021	0.009	-9999	-10000	0	0
VAV1	-0.005	0.16	-9999	-0.43	2	2
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.039	0.14	-9999	-10000	0	0
PTPN11	0.004	0.017	-9999	-10000	0	0
IL6/IL6RA	-0.13	0.25	-9999	-0.5	17	17
gp130 (dimer)/TYK2/TYK2/LMO4	0.041	0.064	-9999	-0.41	1	1
gp130 (dimer)/JAK2/JAK2/LMO4	0.041	0.064	-9999	-0.41	1	1
IL6	-0.2	0.33	-9999	-0.68	17	17
PIAS3	0.013	0.022	-9999	-10000	0	0
PTPRE	-0.001	0.022	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
RAC1	0.017	0.001	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.046	0.15	-9999	-0.29	3	3
LMO4	0.027	0.006	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.013	0.12	-9999	-0.5	1	1
MCL1	0.065	0.1	-9999	-0.68	1	1

×

Stabilization and expansion of the E-cadherin adherens junction

Figure S74. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S74. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0	0.099	-10000	0	-0.28	6	6
epithelial cell differentiation	-0.007	0.049	-10000	0	-0.37	1	1
CYFIP2	0.013	0.022	-10000	0	-10000	0	0
ENAH	0.06	0.052	-10000	0	-10000	0	0
EGFR	-0.066	0.22	-10000	0	-0.69	6	6
EPHA2	0.013	0.022	-10000	0	-10000	0	0
MYO6	0.034	0.053	-10000	0	-0.34	1	1
CTNNB1	0.016	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.03	0.012	-10000	0	-10000	0	0
AQP5	0.003	0.043	-10000	0	-10000	0	0
CTNND1	0.016	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.035	0.051	-10000	0	-0.34	1	1
regulation of calcium-dependent cell-cell adhesion	0.025	0.073	-10000	0	-0.34	2	2
EGF	-0.17	0.31	-10000	0	-0.69	14	14
NCKAP1	0.016	0	-10000	0	-10000	0	0
AQP3	-0.021	0.1	-10000	0	-0.49	2	2
cortical microtubule organization	-0.007	0.049	-10000	0	-0.37	1	1
GO:0000145	0.033	0.049	-10000	0	-0.32	1	1
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.03	0.055	-10000	0	-0.37	1	1
MLLT4	0.016	0	-10000	0	-10000	0	0
ARF6/GDP	-0.01	0.052	-10000	0	-10000	0	0
ARF6	0.016	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.031	0.059	-10000	0	-0.39	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.045	0.049	-10000	0	-0.31	1	1
PVRL2	0.016	0	-10000	0	-10000	0	0
ZYX	0.035	0.052	-10000	0	-0.34	1	1
ARF6/GTP	0.036	0.054	-10000	0	-0.36	1	1
CDH1	0.002	0.095	-10000	0	-0.69	1	1
EGFR/EGFR/EGF/EGF	-0.13	0.2	-10000	0	-0.39	18	18
RhoA/GDP	-0.006	0.046	-10000	0	-0.34	1	1
actin cytoskeleton organization	0.04	0.051	-10000	0	-0.32	1	1
IGF-1R heterotetramer	0.016	0	-10000	0	-10000	0	0
GIT1	0.016	0	-10000	0	-10000	0	0
IGF1R	0.016	0	-10000	0	-10000	0	0
IGF1	-0.26	0.34	-10000	0	-0.69	21	21
DIAPH1	0.002	0.007	-10000	0	-10000	0	0
Wnt receptor signaling pathway	0.007	0.049	0.37	1	-10000	0	1
RHOA	0.016	0	-10000	0	-10000	0	0
RhoA/GTP	-0.01	0.053	-10000	0	-10000	0	0
CTNNA1	0.016	0	-10000	0	-10000	0	0
VCL	0.04	0.052	-10000	0	-0.33	1	1
EFNA1	0.016	0	-10000	0	-10000	0	0
LPP	0.042	0.05	-10000	0	-0.32	1	1
Ephrin A1/EPHA2	-0.006	0.044	-10000	0	-0.33	1	1
SEC6/SEC8	-0.005	0.04	-10000	0	-10000	0	0
MGAT3	0.025	0.074	-10000	0	-0.35	2	2
HGF/MET	-0.005	0.044	-10000	0	-0.33	1	1
HGF	0.013	0.022	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0	0.1	-10000	0	-0.28	6	6
actin cable formation	0.079	0.046	-10000	0	-10000	0	0
KIAA1543	0.042	0.05	-10000	0	-0.32	1	1
KIFC3	0.034	0.053	-10000	0	-0.34	1	1
NCK1	0.002	0.095	-10000	0	-0.69	1	1
EXOC3	0.016	0	-10000	0	-10000	0	0
ACTN1	0.035	0.052	-10000	0	-0.34	1	1
NCK1/GIT1	0.013	0.072	-10000	0	-0.51	1	1
mol:GDP	-0.007	0.049	-10000	0	-0.37	1	1
EXOC4	0.016	0	-10000	0	-10000	0	0
STX4	0.035	0.052	-10000	0	-0.34	1	1
PIP5K1C	0.035	0.052	-10000	0	-0.34	1	1
LIMA1	-0.05	0.2	-10000	0	-0.69	5	5
ABI1	0.016	0	-10000	0	-10000	0	0
ROCK1	0.056	0.059	-10000	0	-10000	0	0
adherens junction assembly	0.059	0.048	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.14	0.18	-10000	0	-0.35	21	21
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.023	0	-10000	0	-10000	0	0
MET	0.013	0.022	-10000	0	-10000	0	0
PLEKHA7	0.035	0.052	-10000	0	-0.34	1	1
mol:GTP	0.029	0.058	-10000	0	-0.39	1	1
establishment of epithelial cell apical/basal polarity	0.061	0.047	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	0	0.099	-10000	0	-0.28	6	6
regulation of cell-cell adhesion	0.04	0.051	-10000	0	-0.32	1	1
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0	0.1	-10000	0	-0.28	6	6

×

IL2 signaling events mediated by STAT5

Figure S75. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S75. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.016	0	-9999	-10000	0	0
ELF1	0.013	0.094	-9999	-0.67	1	1
CCNA2	-0.045	0.079	-9999	-10000	0	0
PIK3CA	0.003	0.095	-9999	-0.69	1	1
JAK3	0.016	0	-9999	-10000	0	0
PIK3R1	0.003	0.095	-9999	-0.69	1	1
JAK1	0.016	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.081	0.084	-9999	-0.53	1	1
SHC1	0.016	0	-9999	-10000	0	0
SP1	-0.006	0.1	-9999	-0.36	4	4
IL2RA	0.026	0.072	-9999	-0.5	1	1
IL2RB	0.016	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
IL2RG	0.017	0	-9999	-10000	0	0
G1/S transition of mitotic cell cycle	-0.044	0.24	-9999	-0.68	6	6
PTPN11	0.017	0	-9999	-10000	0	0
CCND2	-0.038	0.24	-9999	-0.88	4	4
LCK	0.01	0.031	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
IL2	0.017	0	-9999	-10000	0	0
CDK6	-0.024	0.16	-9999	-0.69	3	3
CCND3	0.086	0.074	-9999	-0.45	1	1

×

Class I PI3K signaling events

Figure S76. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S76. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.013	0.081	0.27	1	-0.31	3	4
DAPP1	0.038	0.052	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK	0.06	0.071	-10000	0	-0.42	1	1
mol:DAG	0.052	0.061	0.2	1	-0.2	1	2
HRAS	0.015	0.005	-10000	0	-10000	0	0
RAP1A	-0.023	0.16	-10000	0	-0.69	3	3
ARF5/GDP	-0.017	0.1	-10000	0	-0.29	2	2
PLCG2	-0.011	0.13	-10000	0	-0.69	2	2
PLCG1	0.016	0	-10000	0	-10000	0	0
ARF5	0.016	0	-10000	0	-10000	0	0
mol:GTP	-0.015	0.085	0.24	1	-0.34	3	4
ARF1/GTP	-0.013	0.079	0.24	1	-0.31	3	4
RHOA	0.016	0	-10000	0	-10000	0	0
YES1	0.016	0	-10000	0	-10000	0	0
RAP1A/GTP	-0.015	0.085	0.23	1	-0.34	3	4
ADAP1	-0.014	0.08	0.23	1	-0.32	3	4
ARAP3	-0.015	0.084	0.24	1	-0.33	3	4
INPPL1	0.016	0	-10000	0	-10000	0	0
PREX1	0.016	0	-10000	0	-10000	0	0
ARHGEF6	-0.17	0.31	-10000	0	-0.69	14	14
ARHGEF7	0.016	0	-10000	0	-10000	0	0
ARF1	0.016	0	-10000	0	-10000	0	0
NRAS	0.012	0.022	-10000	0	-10000	0	0
FYN	0.016	0	-10000	0	-10000	0	0
ARF6	0.016	0	-10000	0	-10000	0	0
FGR	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0.037	0.034	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.016	0	-10000	0	-10000	0	0
ZAP70	0.01	0.031	-10000	0	-10000	0	0
mol:IP3	0.044	0.045	-10000	0	-10000	0	0
LYN	0.013	0.022	-10000	0	-10000	0	0
ARF1/GDP	-0.017	0.1	-10000	0	-0.29	2	2
RhoA/GDP	-0.028	0.089	0.25	1	-0.35	3	4
PDK1/Src/Hsp90	0.032	0	-10000	0	-10000	0	0
BLNK	0.016	0	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.002	0.12	-10000	0	-0.38	3	3
SRC	0.016	0	-10000	0	-10000	0	0
PLEKHA2	0.022	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PTEN	0.001	0.092	-10000	0	-0.67	1	1
HSP90AA1	0.016	0	-10000	0	-10000	0	0
ARF6/GTP	-0.013	0.081	0.27	1	-0.31	3	4
RhoA/GTP	-0.014	0.08	0.24	1	-0.32	3	4
Src family/SYK family/BLNK-LAT	0.057	0.034	-10000	0	-10000	0	0
BLK	0.013	0.022	-10000	0	-10000	0	0
PDPK1	0.016	0	-10000	0	-10000	0	0
CYTH1	-0.014	0.08	0.23	1	-0.32	3	4
HCK	0.002	0.095	-10000	0	-0.69	1	1
CYTH3	-0.014	0.08	0.23	1	-0.32	3	4
CYTH2	-0.014	0.08	0.23	1	-0.32	3	4
KRAS	0.015	0.005	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.005	0.045	0.2	1	-10000	0	1
SGK1	-0.006	0.049	0.21	1	-10000	0	1
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.027	0.11	-10000	0	-0.28	3	3
SOS1	0.016	0	-10000	0	-10000	0	0
SYK	0.003	0.043	-10000	0	-10000	0	0
ARF6/GDP	-0.027	0.089	0.26	1	-0.34	3	4
mol:PI-3-4-5-P3	-0.013	0.089	0.33	1	-0.33	3	4
ARAP3/RAP1A/GTP	-0.015	0.084	0.23	1	-0.34	3	4
VAV1	0.002	0.095	-10000	0	-0.69	1	1
mol:PI-3-4-P2	0.013	0	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.008	0.084	-10000	0	-0.34	3	3
PLEKHA1	0.02	0.012	-10000	0	-10000	0	0
Rac1/GDP	-0.017	0.1	-10000	0	-0.29	2	2
LAT	0.016	0	-10000	0	-10000	0	0
Rac1/GTP	-0.048	0.15	-10000	0	-0.3	14	14
ITK	-0.013	0.079	0.24	1	-0.31	3	4
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.059	0.077	0.23	1	-0.27	1	2
LCK	0.01	0.031	-10000	0	-10000	0	0
BTK	-0.02	0.091	0.24	1	-0.32	4	5

×

Arf6 trafficking events

Figure S77. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S77. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.13	0.28	-9999	-0.69	11	11
CLTC	0.033	0.029	-9999	-10000	0	0
calcium ion-dependent exocytosis	0.03	0	-9999	-10000	0	0
Dynamin 2/GTP	0.028	0	-9999	-10000	0	0
EXOC4	0.016	0	-9999	-10000	0	0
CD59	0.028	0.035	-9999	-10000	0	0
CPE	-0.18	0.23	-9999	-0.44	23	23
CTNNB1	0.016	0	-9999	-10000	0	0
membrane fusion	0.03	0	-9999	-10000	0	0
CTNND1	0.035	0	-9999	-10000	0	0
DNM2	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.037	0	-9999	-10000	0	0
TSHR	0.02	0.012	-9999	-10000	0	0
INS	0.023	0	-9999	-10000	0	0
BIN1	0.016	0	-9999	-10000	0	0
mol:Choline	0.03	0	-9999	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-9999	-10000	0	0
mol:GDP	0.021	0	-9999	-10000	0	0
membrane depolarization	0	0	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
mol:Ca2+	0.028	0	-9999	-10000	0	0
JUP	0.033	0	-9999	-10000	0	0
ASAP2/amphiphysin II	0.02	0	-9999	-10000	0	0
ARF6/GTP	0.012	0	-9999	-10000	0	0
CDH1	0.028	0.035	-9999	-10000	0	0
clathrin-independent pinocytosis	0.012	0	-9999	-10000	0	0
MAPK8IP3	-0.001	0.097	-9999	-0.69	1	1
positive regulation of endocytosis	0.012	0	-9999	-10000	0	0
EXOC2	0.016	0	-9999	-10000	0	0
substrate adhesion-dependent cell spreading	0.049	0	-9999	-10000	0	0
insulin receptor binding	0	0	-9999	-10000	0	0
SPAG9	0.016	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.003	0.02	-9999	-10000	0	0
positive regulation of phagocytosis	0.021	0	-9999	-10000	0	0
ARF6/GTP/JIP3	0.011	0.064	-9999	-0.44	1	1
ACAP1	0.026	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CHRM2	0.031	0.007	-9999	-10000	0	0
clathrin heavy chain/ACAP1	0.039	0.022	-9999	-10000	0	0
JIP4/KLC1	0.03	0	-9999	-10000	0	0
EXOC1	0.016	0	-9999	-10000	0	0
exocyst	0.049	0	-9999	-10000	0	0
RALA/GTP	0.012	0	-9999	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.021	0	-9999	-10000	0	0
receptor recycling	0.012	0	-9999	-10000	0	0
CTNNA1	0.035	0	-9999	-10000	0	0
NME1	0.021	0	-9999	-10000	0	0
clathrin coat assembly	0.032	0.029	-9999	-10000	0	0
IL2RA	0.033	0	-9999	-10000	0	0
VAMP3	0.021	0	-9999	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.066	0.13	-9999	-0.32	11	11
EXOC6	0.016	0	-9999	-10000	0	0
PLD1	0.025	0	-9999	-10000	0	0
PLD2	0.025	0	-9999	-10000	0	0
EXOC5	0.016	0	-9999	-10000	0	0
PIP5K1C	0.037	0	-9999	-10000	0	0
SDC1	0.033	0	-9999	-10000	0	0
ARF6/GDP	0.021	0	-9999	-10000	0	0
EXOC7	0.016	0	-9999	-10000	0	0
E-cadherin/beta catenin	-0.003	0.021	-9999	-10000	0	0
mol:Phosphatidic acid	0.03	0	-9999	-10000	0	0
endocytosis	-0.019	0	-9999	-10000	0	0
SCAMP2	0.016	0	-9999	-10000	0	0
ADRB2	-0.27	0.15	-9999	-0.34	44	44
EXOC3	0.016	0	-9999	-10000	0	0
ASAP2	0	0	-9999	-10000	0	0
Dynamin 2/GDP	0.029	0	-9999	-10000	0	0
KLC1	0.016	0	-9999	-10000	0	0
AVPR2	0.039	0.028	-9999	-10000	0	0
RALA	0.016	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.002	0.018	-9999	-10000	0	0

×

Regulation of Telomerase

Figure S78. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S78. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	0.008	0.065	-9999	-10000	0	0
RAD9A	0.016	0	-9999	-10000	0	0
AP1	-0.24	0.27	-9999	-0.51	27	27
IFNAR2	0.018	0.001	-9999	-10000	0	0
AKT1	-0.003	0.084	-9999	-0.24	6	6
ER alpha/Oestrogen	-0.058	0.17	-9999	-0.52	6	6
NFX1/SIN3/HDAC complex	0.054	0.007	-9999	-10000	0	0
EGF	-0.17	0.31	-9999	-0.69	14	14
SMG5	0.016	0	-9999	-10000	0	0
SMG6	0.016	0	-9999	-10000	0	0
SP3/HDAC2	0.028	0.001	-9999	-10000	0	0
TERT/c-Abl	0.016	0.06	-9999	-10000	0	0
SAP18	0.016	0	-9999	-10000	0	0
MRN complex	0.032	0	-9999	-10000	0	0
WT1	-0.088	0.078	-9999	-10000	0	0
WRN	0.016	0	-9999	-10000	0	0
SP1	0.019	0.001	-9999	-10000	0	0
SP3	0.017	0	-9999	-10000	0	0
TERF2IP	0.016	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.009	0.025	-9999	-10000	0	0
Mad/Max	0.026	0.001	-9999	-10000	0	0
TERT	0.008	0.065	-9999	-10000	0	0
CCND1	0.015	0.062	-9999	-10000	0	0
MAX	0.017	0	-9999	-10000	0	0
RBBP7	0.007	0.037	-9999	-10000	0	0
RBBP4	0.016	0	-9999	-10000	0	0
TERF2	0.014	0	-9999	-10000	0	0
PTGES3	0.016	0	-9999	-10000	0	0
SIN3A	0.016	0	-9999	-10000	0	0
Telomerase/911	0.045	0.015	-9999	-10000	0	0
CDKN1B	-0.019	0.21	-9999	-0.75	4	4
RAD1	0.016	0	-9999	-10000	0	0
XRCC5	0.016	0	-9999	-10000	0	0
XRCC6	0.016	0	-9999	-10000	0	0
SAP30	0.016	0	-9999	-10000	0	0
TRF2/PARP2	0.023	0	-9999	-10000	0	0
UBE3A	0.017	0	-9999	-10000	0	0
JUN	0.003	0.095	-9999	-0.69	1	1
E6	0.001	0	-9999	-10000	0	0
HPV-16 E6/E6AP	0.014	0.002	-9999	-10000	0	0
FOS	-0.32	0.35	-9999	-0.69	26	26
IFN-gamma/IRF1	0.005	0.096	-9999	-0.32	4	4
PARP2	0.016	0	-9999	-10000	0	0
BLM	-0.054	0.081	-9999	-10000	0	0
Telomerase	0.007	0.039	-9999	-10000	0	0
IRF1	0.007	0.054	-9999	-10000	0	0
ESR1	-0.08	0.22	-9999	-0.69	6	6
KU/TER	0.023	0	-9999	-10000	0	0
ATM/TRF2	0.024	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.06	0.006	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.061	0.006	-9999	-10000	0	0
HDAC1	0.016	0	-9999	-10000	0	0
HDAC2	0.019	0.001	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.024	0	-9999	-10000	0	0
ABL1	0.016	0	-9999	-10000	0	0
MXD1	0.017	0	-9999	-10000	0	0
MRE11A	0.016	0	-9999	-10000	0	0
HUS1	0.016	0	-9999	-10000	0	0
RPS6KB1	0.016	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	0.003	0.051	-9999	-10000	0	0
NR2F2	-0.013	0.13	-9999	-0.69	2	2
MAPK3	0.028	0.001	-9999	-10000	0	0
MAPK1	0.028	0.001	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.015	0	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
HNRNPC	0.016	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.016	0	-9999	-10000	0	0
EGFR	-0.065	0.22	-9999	-0.69	6	6
mol:Oestrogen	0.001	0	-9999	-10000	0	0
EGF/EGFR	-0.17	0.3	-9999	-0.59	17	17
MYC	0.017	0	-9999	-10000	0	0
IL2	0.019	0.001	-9999	-10000	0	0
KU	0.023	0	-9999	-10000	0	0
RAD50	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
TGFB1	0.015	0	-9999	-10000	0	0
TRF2/BLM	-0.017	0.047	-9999	-10000	0	0
FRAP1	0.016	0	-9999	-10000	0	0
KU/TERT	0.024	0.061	-9999	-10000	0	0
SP1/HDAC2	0.03	0.004	-9999	-10000	0	0
PINX1	0.016	0	-9999	-10000	0	0
Telomerase/EST1A	-0.009	0.025	-9999	-10000	0	0
Smad3/Myc	0.029	0	-9999	-10000	0	0
911 complex	0.032	0	-9999	-10000	0	0
IFNG	-0.001	0.062	-9999	-10000	0	0
Telomerase/PinX1	-0.009	0.025	-9999	-10000	0	0
Telomerase/AKT1/mTOR/p70S6K	0.04	0.034	-9999	-10000	0	0
SIN3B	0.016	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
Telomerase/EST1B	-0.009	0.025	-9999	-10000	0	0
response to DNA damage stimulus	0.004	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0.045	0	-9999	-10000	0	0
TRF2/WRN	0.023	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.009	0.025	-9999	-10000	0	0
E2F1	0	0.051	-9999	-10000	0	0
ZNFX1	0.016	0	-9999	-10000	0	0
PIF1	-0.021	0.068	-9999	-10000	0	0
NCL	0.016	0	-9999	-10000	0	0
DKC1	0.013	0.022	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Syndecan-4-mediated signaling events

Figure S79. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S79. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.034	0.011	-9999	-10000	0	0
Syndecan-4/Syndesmos	0.049	0.018	-9999	-10000	0	0
positive regulation of JNK cascade	-0.27	0.1	-9999	-10000	0	0
Syndecan-4/ADAM12	0.049	0.018	-9999	-10000	0	0
CCL5	0.013	0.022	-9999	-10000	0	0
Rac1/GDP	0.012	0	-9999	-10000	0	0
DNM2	0.016	0	-9999	-10000	0	0
ITGA5	0.016	0	-9999	-10000	0	0
SDCBP	0.016	0	-9999	-10000	0	0
PLG	0.007	0.032	-9999	-10000	0	0
ADAM12	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.005	0.007	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	0.044	0.025	-9999	-10000	0	0
Syndecan-4/CXCL12/CXCR4	-0.28	0.11	-9999	-10000	0	0
Syndecan-4/Laminin alpha3	0.028	0.085	-9999	-10000	0	0
MDK	-0.042	0.078	-9999	-10000	0	0
Syndecan-4/FZD7	-0.17	0.19	-9999	-10000	0	0
Syndecan-4/Midkine	0.037	0.036	-9999	-10000	0	0
FZD7	-0.4	0.35	-9999	-0.69	32	32
Syndecan-4/FGFR1/FGF	-0.21	0.14	-9999	-10000	0	0
THBS1	0.016	0	-9999	-10000	0	0
integrin-mediated signaling pathway	0.047	0.018	-9999	-10000	0	0
positive regulation of MAPKKK cascade	-0.27	0.1	-9999	-10000	0	0
Syndecan-4/TACI	0.049	0.018	-9999	-10000	0	0
CXCR4	0.01	0.031	-9999	-10000	0	0
cell adhesion	0.031	0.009	-9999	-10000	0	0
Syndecan-4/Dynamin	0.049	0.018	-9999	-10000	0	0
Syndecan-4/TSP1	0.049	0.018	-9999	-10000	0	0
Syndecan-4/GIPC	0.047	0.022	-9999	-10000	0	0
Syndecan-4/RANTES	0.047	0.022	-9999	-10000	0	0
ITGB1	0.016	0	-9999	-10000	0	0
LAMA1	-0.009	0.058	-9999	-10000	0	0
LAMA3	-0.024	0.16	-9999	-0.69	3	3
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	0.005	0.008	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	0.049	0.018	-9999	-10000	0	0
TFPI	-0.024	0.16	-9999	-0.69	3	3
F2	0.016	0.002	-9999	-10000	0	0
alpha5/beta1 Integrin	0.023	0	-9999	-10000	0	0
positive regulation of cell adhesion	0.027	0.083	-9999	-10000	0	0
ACTN1	0.016	0	-9999	-10000	0	0
TNC	0.013	0.022	-9999	-10000	0	0
Syndecan-4/CXCL12	-0.29	0.11	-9999	-10000	0	0
FGF6	0.013	0.022	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CXCL12	-0.62	0.2	-9999	-0.69	49	49
TNFRSF13B	0.016	0	-9999	-10000	0	0
FGF2	-0.48	0.32	-9999	-0.69	38	38
FGFR1	0.013	0.022	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2	0.038	0.018	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.007	0.032	-9999	-10000	0	0
cell migration	-0.002	0.004	-9999	-10000	0	0
PRKCD	0.013	0.004	-9999	-10000	0	0
vasculogenesis	0.048	0.018	-9999	-10000	0	0
SDC4	0.041	0.02	-9999	-10000	0	0
Syndecan-4/Tenascin C	0.048	0.018	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2/PKC alpha	-0.004	0.006	-9999	-10000	0	0
Syndecan-4/Syntenin	0.049	0.018	-9999	-10000	0	0
MMP9	-0.016	0.066	-9999	-10000	0	0
Rac1/GTP	0.032	0.01	-9999	-10000	0	0
cytoskeleton organization	0.048	0.018	-9999	-10000	0	0
GIPC1	0.013	0.022	-9999	-10000	0	0
Syndecan-4/TFPI	0.028	0.085	-9999	-10000	0	0

×

VEGFR1 specific signals

Figure S80. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S80. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.022	0.11	-9999	-0.78	1	1
VEGFR1 homodimer/NRP1	0.011	0.11	-9999	-0.79	1	1
mol:DAG	0.031	0.1	-9999	-0.71	1	1
VEGFR1 homodimer/NRP1/VEGFR 121	-0.012	0.11	-9999	-0.73	1	1
CaM/Ca2+	0.037	0.098	-9999	-0.67	1	1
HIF1A	0.018	0.052	-9999	-0.36	1	1
GAB1	0.002	0.095	-9999	-0.69	1	1
AKT1	0.036	0.15	-9999	-0.73	2	2
PLCG1	0.031	0.1	-9999	-0.72	1	1
NOS3	0.055	0.095	-9999	-0.61	1	1
CBL	0.016	0	-9999	-10000	0	0
mol:NO	0.054	0.092	-9999	-0.58	1	1
FLT1	0.018	0.12	-9999	-0.88	1	1
PGF	0.016	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP2/VEGFR121	-0.005	0.11	-9999	-0.72	1	1
CALM1	0.016	0	-9999	-10000	0	0
PIK3CA	0.002	0.095	-9999	-0.69	1	1
eNOS/Hsp90	0.061	0.089	-9999	-0.56	1	1
endothelial cell proliferation	0.038	0.099	-9999	-0.68	1	1
mol:Ca2+	0.031	0.1	-9999	-0.7	1	1
MAPK3	0.043	0.091	-9999	-0.62	1	1
MAPK1	0.043	0.091	-9999	-0.62	1	1
PIK3R1	0.002	0.095	-9999	-0.69	1	1
PLGF homodimer	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.51	0.31	-9999	-0.69	40	40
VEGFA homodimer	-0.054	0.08	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	-0.014	0.11	-9999	-0.78	1	1
platelet activating factor biosynthetic process	0.05	0.089	-9999	-0.6	1	1
PI3K	0.024	0.14	-9999	-0.71	2	2
PRKCA	0.037	0.096	-9999	-0.66	1	1
PRKCB	0.028	0.095	-9999	-0.67	1	1
VEGFR1 homodimer/PLGF homodimer	0.022	0.11	-9999	-0.78	1	1
VEGFA	-0.054	0.081	-9999	-10000	0	0
VEGFB	0.016	0	-9999	-10000	0	0
mol:IP3	0.031	0.1	-9999	-0.71	1	1
RASA1	0.031	0.1	-9999	-0.72	1	1
NRP2	0.01	0.031	-9999	-10000	0	0
VEGFR1 homodimer	0.018	0.12	-9999	-0.88	1	1
VEGFB homodimer	0.016	0	-9999	-10000	0	0
NCK1	0.002	0.095	-9999	-0.69	1	1
eNOS/Caveolin-1	-0.21	0.19	-9999	-0.68	2	2
PTPN11	0.016	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.023	0.14	-9999	-0.7	2	2
mol:L-citrulline	0.054	0.092	-9999	-0.58	1	1
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.033	0.099	-9999	-0.69	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.01	0.12	-9999	-0.59	2	2
CD2AP	0.016	0	-9999	-10000	0	0
PI3K/GAB1	0.024	0.18	-9999	-0.84	2	2
PDPK1	0.029	0.13	-9999	-0.65	2	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.002	0.11	-9999	-0.72	1	1
mol:NADP	0.054	0.092	-9999	-0.58	1	1
HSP90AA1	0.016	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.031	0.097	-9999	-0.68	1	1
VEGFR1 homodimer/NRP2	0.019	0.11	-9999	-0.78	1	1

×

S1P3 pathway

Figure S81. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S81. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-9999	-10000	0	0
mol:S1P	0.002	0	-9999	-10000	0	0
S1P1/S1P/Gi	-0.13	0.19	-9999	-0.68	3	3
GNAO1	0.018	0	-9999	-10000	0	0
S1P/S1P3/G12/G13	0.023	0	-9999	-10000	0	0
AKT1	0.031	0.035	-9999	-10000	0	0
AKT3	0.032	0.062	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.016	0	-9999	-10000	0	0
GNAI2	0.018	0	-9999	-10000	0	0
GNAI3	0.004	0.095	-9999	-0.69	1	1
GNAI1	-0.022	0.16	-9999	-0.69	3	3
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.002	0	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	-0.39	0.35	-9999	-0.69	31	31
mol:Ca2+	0.023	0.1	-9999	-0.35	3	3
MAPK3	0.03	0.097	-9999	-0.58	1	1
MAPK1	0.03	0.097	-9999	-0.58	1	1
JAK2	0.033	0.096	-9999	-0.57	1	1
CXCR4	0.027	0.097	-9999	-0.58	1	1
FLT1	0.006	0.095	-9999	-0.69	1	1
RhoA/GDP	0.012	0	-9999	-10000	0	0
Rac1/GDP	0.012	0	-9999	-10000	0	0
SRC	0.03	0.097	-9999	-0.58	1	1
S1P/S1P3/Gi	0.023	0.1	-9999	-0.36	3	3
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	0.028	0.093	-9999	-0.56	1	1
VEGFA	-0.051	0.081	-9999	-10000	0	0
S1P/S1P2/Gi	0.018	0.1	-9999	-0.36	3	3
VEGFR1 homodimer/VEGFA homodimer	-0.024	0.086	-9999	-0.51	1	1
RHOA	0.016	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.017	0.043	-9999	-0.3	1	1
GNAQ	0	0	-9999	-10000	0	0
GNAZ	0.017	0	-9999	-10000	0	0
G12/G13	0.023	0	-9999	-10000	0	0
GNA14	0.002	0.095	-9999	-0.69	1	1
GNA15	0.016	0	-9999	-10000	0	0
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.016	0	-9999	-10000	0	0
Rac1/GTP	0.028	0.093	-9999	-0.56	1	1

×

Visual signal transduction: Rods

Figure S82. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S82. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.016	0	-9999	-10000	0	0
GNAT1/GTP	0.012	0	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.001	0.089	-9999	-0.44	2	2
PDE6G/GNAT1/GTP	0.02	0.012	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.016	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
CNG Channel	-0.06	0.13	-9999	-0.33	10	10
mol:Na +	-0.058	0.13	-9999	-0.37	1	1
mol:ADP	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.02	0.029	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.059	0.13	-9999	-0.38	1	1
CNGB1	0.016	0	-9999	-10000	0	0
RDH5	-0.28	0.35	-9999	-0.69	23	23
SAG	-0.02	0.14	-9999	-0.69	2	2
mol:Ca2+	-0.009	0.14	-9999	-0.36	1	1
Na + (4 Units)	-0.054	0.12	-9999	-0.35	1	1
RGS9	0.016	0	-9999	-10000	0	0
GNB1/GNGT1	-0.051	0.048	-9999	-10000	0	0
GNAT1/GDP	0.027	0.025	-9999	-10000	0	0
GUCY2D	0.016	0	-9999	-10000	0	0
GNGT1	-0.099	0.074	-9999	-10000	0	0
GUCY2F	0.009	0.031	-9999	-10000	0	0
GNB5	0.006	0.037	-9999	-10000	0	0
mol:GMP (4 units)	0.035	0.01	-9999	-10000	0	0
mol:11-cis-retinal	-0.28	0.35	-9999	-0.69	23	23
mol:cGMP	0.043	0.014	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
Rhodopsin	-0.2	0.26	-9999	-0.51	23	23
SLC24A1	0.016	0	-9999	-10000	0	0
CNGA1	-0.12	0.27	-9999	-0.69	10	10
Metarhodopsin II	0.01	0	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.039	0.011	-9999	-10000	0	0
RGS9BP	0.003	0.043	-9999	-10000	0	0
Metarhodopsin II/Transducin	-0.002	0.019	-9999	-10000	0	0
GCAP Family/Ca ++	0.029	0.011	-9999	-10000	0	0
PDE6A/B	0.023	0	-9999	-10000	0	0
mol:Pi	0.02	0.029	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.025	0.036	-9999	-10000	0	0
PDE6B	0.016	0	-9999	-10000	0	0
PDE6A	0.016	0	-9999	-10000	0	0
PDE6G	0.013	0.022	-9999	-10000	0	0
RHO	0.016	0	-9999	-10000	0	0
PDE6	0.005	0.012	-9999	-10000	0	0
GUCA1A	0.016	0	-9999	-10000	0	0
GC2/GCAP Family	0.036	0.018	-9999	-10000	0	0
GUCA1C	0.013	0.022	-9999	-10000	0	0
GUCA1B	0.016	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

Figure S83. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S83. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.039	0.1	-10000	0	-0.67	1	1
adherens junction organization	0.037	0.048	-10000	0	-0.26	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.009	0.16	-10000	0	-0.85	1	1
FMN1	0.032	0.047	-10000	0	-0.26	1	1
mol:IP3	0.031	0.095	-10000	0	-0.64	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.034	0.05	-10000	0	-0.27	1	1
CTNNB1	0.015	0.002	-10000	0	-10000	0	0
AKT1	0.038	0.096	-10000	0	-0.63	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.04	0.065	-10000	0	-0.42	1	1
CTNND1	0.016	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.039	0.047	-10000	0	-10000	0	0
VASP	0.034	0.05	-10000	0	-0.25	1	1
ZYX	0.04	0.047	-10000	0	-0.25	1	1
JUB	0.04	0.047	-10000	0	-0.25	1	1
EGFR(dimer)	-0.002	0.14	-10000	0	-0.35	7	7
E-cadherin/beta catenin-gamma catenin	-0.007	0.057	-10000	0	-0.42	1	1
mol:PI-3-4-5-P3	0.03	0.1	-10000	0	-0.68	1	1
PIK3CA	0.003	0.098	-10000	0	-0.71	1	1
PI3K	0.031	0.1	-10000	0	-0.7	1	1
FYN	0.047	0.082	-10000	0	-0.53	1	1
mol:Ca2+	0.031	0.093	-10000	0	-0.62	1	1
JUP	0.015	0.002	-10000	0	-10000	0	0
PIK3R1	0.003	0.098	-10000	0	-0.71	1	1
mol:DAG	0.031	0.095	-10000	0	-0.64	1	1
CDH1	0.002	0.095	-10000	0	-0.69	1	1
RhoA/GDP	0.009	0.16	-10000	0	-0.85	1	1
establishment of polarity of embryonic epithelium	0.034	0.049	-10000	0	-0.25	1	1
SRC	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
EGFR	-0.066	0.22	-10000	0	-0.69	6	6
CASR	0.038	0.088	-10000	0	-0.58	1	1
RhoA/GTP	-0.013	0.077	-10000	0	-0.56	1	1
AKT2	0.038	0.096	-10000	0	-0.63	1	1
actin cable formation	0.033	0.049	-10000	0	-0.24	1	1
apoptosis	-0.036	0.096	0.63	1	-10000	0	1
CTNNA1	0.016	0.002	-10000	0	-10000	0	0
mol:GDP	-0.002	0.17	-10000	0	-0.42	6	6
PIP5K1A	0.039	0.048	-10000	0	-10000	0	0
PLCG1	0.031	0.098	-10000	0	-0.66	1	1
Rac1/GTP	-0.04	0.11	-10000	0	-0.33	6	6
homophilic cell adhesion	0.001	0.003	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

Figure S84. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S84. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.004	0.11	-9999	-0.44	3	3
ADCY5	0.022	0	-9999	-10000	0	0
ADCY6	0.022	0	-9999	-10000	0	0
ADCY7	0.022	0	-9999	-10000	0	0
ADCY1	0.022	0	-9999	-10000	0	0
ADCY2	0.022	0	-9999	-10000	0	0
ADCY3	0.022	0	-9999	-10000	0	0
ADCY8	0.022	0	-9999	-10000	0	0
PRKCE	0.013	0	-9999	-10000	0	0
ADCY9	0.022	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	0.032	0.041	-9999	-10000	0	0

×

ErbB2/ErbB3 signaling events

Figure S85. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S85. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.022	0.001	-9999	-10000	0	0
RAS family/GTP	0.033	0.034	-9999	-10000	0	0
NFATC4	0.028	0.03	-9999	-10000	0	0
ERBB2IP	0.015	0.001	-9999	-10000	0	0
HSP90 (dimer)	0.016	0	-9999	-10000	0	0
mammary gland morphogenesis	0.024	0.026	-9999	-10000	0	0
JUN	0.007	0.082	-9999	-10000	0	0
HRAS	0.015	0.001	-9999	-10000	0	0
DOCK7	0.027	0.029	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.015	0.021	-9999	-10000	0	0
AKT1	0.013	0.001	-9999	-10000	0	0
BAD	0.021	0.012	-9999	-10000	0	0
MAPK10	0.039	0.013	-9999	-10000	0	0
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.026	0.029	-9999	-10000	0	0
RAF1	0.039	0.046	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 2	-0.084	0.18	-9999	-0.41	12	12
STAT3	0.001	0.004	-9999	-10000	0	0
cell migration	0.044	0.026	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
cell proliferation	-0.065	0.2	-9999	-0.54	1	1
FOS	-0.18	0.3	-9999	-0.49	27	27
NRAS	0.012	0.022	-9999	-10000	0	0
mol:Ca2+	0.024	0.026	-9999	-10000	0	0
MAPK3	-0.016	0.14	-9999	-0.4	1	1
MAPK1	-0.016	0.14	-9999	-0.4	1	1
JAK2	0.027	0.029	-9999	-10000	0	0
NF2	0.001	0.003	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.032	0.007	-9999	-10000	0	0
NRG1	0.015	0.002	-9999	-10000	0	0
GRB2/SOS1	0.023	0.001	-9999	-10000	0	0
MAPK8	0.03	0.032	-9999	-10000	0	0
MAPK9	0.034	0.037	-9999	-0.22	1	1
ERBB2	-0.004	0.019	-9999	-10000	0	0
ERBB3	0.015	0.002	-9999	-10000	0	0
SHC1	0.015	0.001	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
apoptosis	0.005	0.009	-9999	-10000	0	0
STAT3 (dimer)	0.025	0.001	-9999	-10000	0	0
RNF41	0.029	0.002	-9999	-10000	0	0
FRAP1	0.022	0.001	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0.002	-9999	-10000	0	0
ErbB2/ErbB2/HSP90 (dimer)	-0.003	0.013	-9999	-10000	0	0
CHRNA1	-0.008	0.12	-9999	-0.31	1	1
myelination	0.049	0.018	-9999	-10000	0	0
PPP3CB	0.026	0.028	-9999	-10000	0	0
KRAS	0.015	0.001	-9999	-10000	0	0
RAC1-CDC42/GDP	0.046	0.006	-9999	-10000	0	0
NRG2	-0.14	0.29	-9999	-0.69	12	12
mol:GDP	0.032	0.007	-9999	-10000	0	0
SOS1	0.015	0.001	-9999	-10000	0	0
MAP2K2	0.042	0.053	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.026	0.028	-9999	-10000	0	0
MAP2K1	-0.029	0.14	-9999	-10000	0	0
heart morphogenesis	0.024	0.026	-9999	-10000	0	0
RAS family/GDP	0.032	0.031	-9999	-10000	0	0
GRB2	0.015	0.001	-9999	-10000	0	0
PRKACA	0	0.002	-9999	-10000	0	0
CHRNE	0.017	0.018	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
activation of caspase activity	-0.013	0.001	-9999	-10000	0	0
nervous system development	0.024	0.026	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

Figure S86. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S86. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.016	0	-9999	-10000	0	0
SMAD2	0.007	0.057	-9999	-0.27	2	2
SMAD3	0.037	0.05	-9999	-10000	0	0
SMAD3/SMAD4	0.048	0.021	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0.03	0.012	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0.034	0.051	-9999	-10000	0	0
PPM1A	0.016	0	-9999	-10000	0	0
CALM1	0.016	0	-9999	-10000	0	0
SMAD2/SMAD4	0.016	0.052	-9999	-0.24	2	2
MAP3K1	0.002	0.095	-9999	-0.69	1	1
TRAP-1/SMAD4	0.023	0	-9999	-10000	0	0
MAPK3	0.016	0	-9999	-10000	0	0
MAPK1	0.016	0	-9999	-10000	0	0
NUP214	0.016	0	-9999	-10000	0	0
CTDSP1	0.016	0	-9999	-10000	0	0
CTDSP2	0.016	0	-9999	-10000	0	0
CTDSPL	-0.011	0.13	-9999	-0.69	2	2
KPNB1	0.016	0	-9999	-10000	0	0
TGFBRAP1	0.016	0	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
NUP153	0.016	0	-9999	-10000	0	0
KPNA2	-0.003	0.051	-9999	-10000	0	0
PIAS4	0.013	0.022	-9999	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

Figure S87. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S87. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	-0.024	0	-9999	-10000	0	0
KIRREL	0.017	0	-9999	-10000	0	0
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.024	0	-9999	-10000	0	0
PLCG1	0.016	0	-9999	-10000	0	0
ARRB2	0.016	0	-9999	-10000	0	0
WASL	0.015	0.002	-9999	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.039	0	-9999	-10000	0	0
ChemicalAbstracts:57-88-5	0	0	-9999	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.037	0.043	-9999	-0.27	1	1
FYN	0.031	0	-9999	-10000	0	0
mol:Ca2+	0.037	0	-9999	-10000	0	0
mol:DAG	0.038	0	-9999	-10000	0	0
NPHS2	0.017	0	-9999	-10000	0	0
mol:IP3	0.038	0	-9999	-10000	0	0
regulation of endocytosis	0.039	0	-9999	-10000	0	0
Nephrin/NEPH1/podocin/Cholesterol	0.029	0	-9999	-10000	0	0
establishment of cell polarity	0.024	0	-9999	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2	0.039	0.058	-9999	-0.38	1	1
Nephrin/NEPH1/beta Arrestin2	0.041	0	-9999	-10000	0	0
NPHS1	0.017	0	-9999	-10000	0	0
Nephrin/NEPH1/podocin	0.033	0	-9999	-10000	0	0
TJP1	0.016	0	-9999	-10000	0	0
NCK1	0.002	0.095	-9999	-0.69	1	1
NCK2	0.016	0	-9999	-10000	0	0
heterophilic cell adhesion	0	0	-9999	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.039	0	-9999	-10000	0	0
CD2AP	0.016	0	-9999	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.039	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
homophilic cell adhesion	0	0	-9999	-10000	0	0
TRPC6	0.027	0.057	-9999	-0.39	1	1
cytoskeleton organization	0.046	0.036	-9999	-10000	0	0
Nephrin/NEPH1	0.02	0	-9999	-10000	0	0
Nephrin/NEPH1/ZO-1	0.032	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

Figure S88. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S88. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.096	0.006	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
RIP2/NOD2	0.021	0.014	-9999	-10000	0	0
NFKBIA	0.051	0	-9999	-10000	0	0
BIRC2	0.016	0	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
RIPK2	0.013	0.022	-9999	-10000	0	0
IKBKG	0.051	0.008	-9999	-10000	0	0
IKK complex/A20	0.06	0.051	-9999	-10000	0	0
NEMO/A20/RIP2	0.013	0.022	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
NEMO/ATM	0.058	0.007	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.021	0	-9999	-10000	0	0
IKK complex/ELKS	0	0.003	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0.03	0.012	-9999	-10000	0	0
NOD2	0.016	0	-9999	-10000	0	0
NFKB1	0.019	0	-9999	-10000	0	0
RELA	0.019	0	-9999	-10000	0	0
MALT1	0.013	0.022	-9999	-10000	0	0
cIAP1/UbcH5C	0.023	0	-9999	-10000	0	0
ATM	0.016	0	-9999	-10000	0	0
TNF/TNFR1A	0.007	0.075	-9999	-0.51	1	1
TRAF6	0.016	0	-9999	-10000	0	0
PRKCA	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
UBE2D3	0.016	0	-9999	-10000	0	0
TNF	0.006	0.037	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.045	0	-9999	-10000	0	0
BCL10	0.016	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.051	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.019	0	-9999	-10000	0	0
TNFRSF1A	0.002	0.095	-9999	-0.69	1	1
IKK complex	0.065	0.007	-9999	-10000	0	0
CYLD	0.016	0	-9999	-10000	0	0
IKK complex/PKC alpha	0.069	0.006	-9999	-10000	0	0

×

BARD1 signaling events

Figure S89. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S89. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.021	0.014	-9999	-10000	0	0
ATM	0.016	0	-9999	-10000	0	0
UBE2D3	0.016	0	-9999	-10000	0	0
PRKDC	0.013	0.022	-9999	-10000	0	0
ATR	0.016	0	-9999	-10000	0	0
UBE2L3	0.016	0	-9999	-10000	0	0
FANCD2	0.029	0	-9999	-10000	0	0
protein ubiquitination	0.005	0.041	-9999	-10000	0	0
XRCC5	0.016	0	-9999	-10000	0	0
XRCC6	0.016	0	-9999	-10000	0	0
M/R/N Complex	0.032	0	-9999	-10000	0	0
MRE11A	0.016	0	-9999	-10000	0	0
DNA-PK	0.03	0.012	-9999	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.033	0.042	-9999	-10000	0	0
FANCF	0.002	0.095	-9999	-0.69	1	1
BRCA1	0.013	0.022	-9999	-10000	0	0
CCNE1	-0.066	0.081	-9999	-10000	0	0
CDK2/Cyclin E1	-0.035	0.062	-9999	-10000	0	0
FANCG	0.016	0	-9999	-10000	0	0
BRCA1/BACH1/BARD1	0.019	0.027	-9999	-10000	0	0
FANCE	0.016	0	-9999	-10000	0	0
FANCC	0.006	0.037	-9999	-10000	0	0
NBN	0.016	0	-9999	-10000	0	0
FANCA	-0.06	0.081	-9999	-10000	0	0
DNA repair	0.023	0.066	-9999	-10000	0	0
BRCA1/BARD1/ubiquitin	0.019	0.027	-9999	-10000	0	0
BARD1/DNA-PK	0.037	0.015	-9999	-10000	0	0
FANCL	0.016	0	-9999	-10000	0	0
mRNA polyadenylation	-0.021	0.014	-9999	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0.044	0.01	-9999	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	0.029	0.023	-9999	-10000	0	0
BRCA1/BARD1/P53	0.037	0.021	-9999	-10000	0	0
BARD1/CSTF1/BRCA1	0.029	0.023	-9999	-10000	0	0
BRCA1/BACH1	0.013	0.022	-9999	-10000	0	0
BARD1	0.013	0.022	-9999	-10000	0	0
PCNA	0.013	0.022	-9999	-10000	0	0
BRCA1/BARD1/UbcH5C	0.029	0.023	-9999	-10000	0	0
BRCA1/BARD1/UbcH7	0.029	0.023	-9999	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	0.001	0.053	-9999	-10000	0	0
BARD1/DNA-PK/P53	0.046	0.003	-9999	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.019	0.027	-9999	-10000	0	0
BRCA1/BARD1/CTIP	0.036	0.021	-9999	-10000	0	0
FA complex	0.023	0.044	-9999	-10000	0	0
BARD1/EWS	0.021	0.014	-9999	-10000	0	0
RBBP8	0.026	0	-9999	-10000	0	0
TP53	0.016	0	-9999	-10000	0	0
TOPBP1	0.016	0	-9999	-10000	0	0
G1/S transition of mitotic cell cycle	-0.036	0.021	-9999	-10000	0	0
BRCA1/BARD1	0.03	0.045	-9999	-10000	0	0
CSTF1	0.016	0	-9999	-10000	0	0
BARD1/EWS-Fli1	0.01	0.014	-9999	-10000	0	0
CDK2	0.006	0.037	-9999	-10000	0	0
UniProt:Q9BZD1	0	0	-9999	-10000	0	0
RAD51	-0.057	0.081	-9999	-10000	0	0
RAD50	0.016	0	-9999	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.019	0.027	-9999	-10000	0	0
EWSR1	0.016	0	-9999	-10000	0	0

×

Syndecan-1-mediated signaling events

Figure S90. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S90. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.016	0	-9999	-10000	0	0
CCL5	0.013	0.022	-9999	-10000	0	0
SDCBP	0.016	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.021	0.096	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.018	0.095	-9999	-0.3	1	1
Syndecan-1/Syntenin	-0.011	0.091	-9999	-10000	0	0
MAPK3	0.003	0.084	-9999	-10000	0	0
HGF/MET	0.019	0.02	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.016	0	-9999	-10000	0	0
BSG	0.016	0	-9999	-10000	0	0
keratinocyte migration	-0.018	0.094	-9999	-0.3	1	1
Syndecan-1/RANTES	-0.012	0.092	-9999	-10000	0	0
Syndecan-1/CD147	-0.004	0.088	-9999	-10000	0	0
Syndecan-1/Syntenin/PIP2	-0.011	0.087	-9999	-10000	0	0
LAMA5	-0.006	0.055	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.011	0.086	-9999	-10000	0	0
MMP7	-0.12	0.25	-9999	-0.69	8	8
HGF	0.013	0.022	-9999	-10000	0	0
Syndecan-1/CASK	-0.021	0.09	-9999	-10000	0	0
Syndecan-1/HGF/MET	-0.002	0.088	-9999	-10000	0	0
regulation of cell adhesion	0.011	0.082	-9999	-10000	0	0
HPSE	0.013	0.022	-9999	-10000	0	0
positive regulation of cell migration	-0.021	0.096	-9999	-10000	0	0
SDC1	-0.021	0.096	-9999	-10000	0	0
Syndecan-1/Collagen	-0.021	0.096	-9999	-10000	0	0
PPIB	0.01	0.031	-9999	-10000	0	0
MET	0.013	0.022	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
MMP9	-0.018	0.066	-9999	-10000	0	0
MAPK1	0.003	0.084	-9999	-10000	0	0
homophilic cell adhesion	-0.021	0.095	-9999	-10000	0	0
MMP1	-0.033	0.074	-9999	-10000	0	0

×

Visual signal transduction: Cones

Figure S91. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S91. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.026	0.01	-9999	-10000	0	0
RGS9BP	0.003	0.043	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
mol:Na +	0.009	0.064	-9999	-0.44	1	1
mol:ADP	0.013	0	-9999	-10000	0	0
GNAT2	0.013	0.022	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.02	0.029	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.018	0.016	-9999	-10000	0	0
GRK7	0.016	0	-9999	-10000	0	0
CNGB3	-0.004	0.099	-9999	-0.69	1	1
Cone Metarhodopsin II/X-Arrestin	0.012	0	-9999	-10000	0	0
mol:Ca2+	0.01	0.082	-9999	-0.4	2	2
Cone PDE6	0.042	0.02	-9999	-10000	0	0
Cone Metarhodopsin II	0.01	0	-9999	-10000	0	0
Na + (4 Units)	0.011	0.082	-9999	-0.4	2	2
GNAT2/GDP	0.026	0.026	-9999	-10000	0	0
GNB5	0.006	0.037	-9999	-10000	0	0
mol:GMP (4 units)	0.026	0.015	-9999	-10000	0	0
Cone Transducin	0.029	0.011	-9999	-10000	0	0
SLC24A2	0.002	0.095	-9999	-0.69	1	1
GNB3/GNGT2	0.023	0	-9999	-10000	0	0
GNB3	0.016	0	-9999	-10000	0	0
GNAT2/GTP	0.01	0.014	-9999	-10000	0	0
CNGA3	0.016	0	-9999	-10000	0	0
ARR3	0.016	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	0.009	0.064	-9999	-0.44	1	1
mol:Pi	0.02	0.029	-9999	-10000	0	0
Cone CNG Channel	-0.004	0.048	-9999	-0.35	1	1
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0.002	0.095	-9999	-0.69	1	1
RGS9	0.016	0	-9999	-10000	0	0
PDE6C	0.016	0	-9999	-10000	0	0
GNGT2	0.016	0	-9999	-10000	0	0
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.013	0.022	-9999	-10000	0	0

×

Circadian rhythm pathway

Figure S92. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S92. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.036	0.044	-9999	-10000	0	0
CLOCK	0.019	0.002	-9999	-10000	0	0
TIMELESS/CRY2	0.041	0.031	-9999	-10000	0	0
DEC1/BMAL1	0.013	0.073	-9999	-0.51	1	1
ATR	0.016	0	-9999	-10000	0	0
NR1D1	0.042	0.023	-9999	-10000	0	0
ARNTL	0.006	0.095	-9999	-0.68	1	1
TIMELESS	0.038	0.035	-9999	-10000	0	0
NPAS2	0.019	0.002	-9999	-10000	0	0
CRY2	0.016	0	-9999	-10000	0	0
mol:CO	-0.013	0.009	-9999	-10000	0	0
CHEK1	-0.063	0.081	-9999	-10000	0	0
mol:HEME	0.013	0.009	-9999	-10000	0	0
PER1	0.016	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.039	0.065	-9999	-0.42	1	1
BMAL1/CLOCK	0.049	0.067	-9999	-10000	0	0
S phase of mitotic cell cycle	0.036	0.044	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.037	0.045	-9999	-10000	0	0
mol:NADPH	0.013	0.009	-9999	-10000	0	0
PER1/TIMELESS	0.041	0.031	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0.012	0.022	-9999	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

Figure S93. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S93. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.016	0	-9999	-10000	0	0
VLDLR	0.016	0	-9999	-10000	0	0
LRPAP1	0.016	0	-9999	-10000	0	0
NUDC	0.016	0	-9999	-10000	0	0
RELN/LRP8	-0.007	0.046	-9999	-10000	0	0
CaM/Ca2+	0.012	0	-9999	-10000	0	0
KATNA1	0.016	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	0.003	0.041	-9999	-10000	0	0
IQGAP1/CaM	0.023	0	-9999	-10000	0	0
DAB1	0.016	0	-9999	-10000	0	0
IQGAP1	0.016	0	-9999	-10000	0	0
PLA2G7	-0.014	0.13	-9999	-0.69	2	2
CALM1	0.016	0	-9999	-10000	0	0
DYNLT1	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.019	0.051	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.016	0	-9999	-10000	0	0
CDK5R1	0.016	0	-9999	-10000	0	0
LIS1/Poliovirus Protein 3A	0.019	0	-9999	-10000	0	0
CDK5R2	0.016	0	-9999	-10000	0	0
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	0.029	0.016	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
NDEL1/14-3-3 E	0.04	0.031	-9999	-10000	0	0
MAP1B	-0.031	0.098	-9999	-0.34	5	5
RAC1	0.025	0	-9999	-10000	0	0
p35/CDK5	0.02	0.036	-9999	-10000	0	0
RELN	0.01	0.031	-9999	-10000	0	0
PAFAH/LIS1	0.012	0.088	-9999	-0.44	2	2
LIS1/CLIP170	0.031	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	0	0.003	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	0.04	0.012	-9999	-10000	0	0
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	0.031	0.034	-9999	-10000	0	0
LIS1/IQGAP1	0.031	0	-9999	-10000	0	0
RHOA	0.025	0	-9999	-10000	0	0
PAFAH1B1	0.026	0	-9999	-10000	0	0
PAFAH1B3	-0.015	0.063	-9999	-10000	0	0
PAFAH1B2	0.016	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.007	0.069	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	0.046	0.03	-9999	-10000	0	0
LRP8	-0.051	0.08	-9999	-10000	0	0
NDEL1/Katanin 60	0.04	0.031	-9999	-10000	0	0
P39/CDK5	0.02	0.036	-9999	-10000	0	0
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.031	0	-9999	-10000	0	0
CDK5	0.012	0.038	-9999	-10000	0	0
PPP2R5D	0.016	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.027	0	-9999	-10000	0	0
CSNK2A1	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	0.046	0.003	-9999	-10000	0	0
RELN/VLDLR	0.005	0.042	-9999	-10000	0	0
CDC42	0.025	0	-9999	-10000	0	0

×

Ephrin A reverse signaling

Figure S94. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S94. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
MAPKKK cascade	0.021	-9999	-9999
EFNA5	0.016	-9999	-9999
FYN	0.029	-9999	-9999
neuron projection morphogenesis	0.021	-9999	-9999
cell-cell signaling	0	-9999	-9999
Ephrin A5/EPHA5	0.021	-9999	-9999
EPHA5	0.016	-9999	-9999

×

JNK signaling in the CD4+ TCR pathway

Figure S95. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S95. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.024	0.081	-9999	-0.39	2	2
MAP4K1	0.016	0	-9999	-10000	0	0
MAP3K8	-0.037	0.18	-9999	-0.69	4	4
PRKCB	0	0	-9999	-10000	0	0
DBNL	0.016	0	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
MAP3K1	0.033	0.077	-9999	-0.35	1	1
JUN	0.022	0.056	-9999	-0.36	1	1
MAP3K7	0.041	0.057	-9999	-10000	0	0
GRAP2	0.016	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
MAP2K4	0.033	0.073	-9999	-10000	0	0
LAT	0.016	0	-9999	-10000	0	0
LCP2	-0.011	0.13	-9999	-0.69	2	2
MAPK8	0.022	0.022	-9999	-10000	0	0
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.034	0.06	-9999	-10000	0	0
LAT/GRAP2/SLP76/HPK1/HIP-55	0.031	0.077	-9999	-0.36	2	2

×

Noncanonical Wnt signaling pathway

Figure S96. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S96. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.016	0	-9999	-10000	0	0
GNB1/GNG2	0.033	0.059	-9999	-10000	0	0
mol:DAG	0.038	0.055	-9999	-10000	0	0
PLCG1	0.039	0.056	-9999	-10000	0	0
YES1	0.024	0.061	-9999	-10000	0	0
FZD3	0.006	0.037	-9999	-10000	0	0
FZD6	0.002	0.095	-9999	-0.69	1	1
G protein	0.04	0.057	-9999	-10000	0	0
MAP3K7	0.05	0.049	-9999	-10000	0	0
mol:Ca2+	0.038	0.054	-9999	-10000	0	0
mol:IP3	0.038	0.055	-9999	-10000	0	0
NLK	0.028	0.006	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
CAMK2A	0.044	0.052	-9999	-10000	0	0
MAP3K7IP1	0.016	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	0.017	0.064	-9999	-10000	0	0
CSNK1A1	0.016	0	-9999	-10000	0	0
GNAS	0.024	0.061	-9999	-10000	0	0
GO:0007205	0.037	0.054	-9999	-10000	0	0
WNT6	0.003	0.043	-9999	-10000	0	0
WNT4	0.002	0.095	-9999	-0.69	1	1
NFAT1/CK1 alpha	0.048	0.054	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
WNT5A	-0.015	0.063	-9999	-10000	0	0
WNT11	0.01	0.031	-9999	-10000	0	0
CDC42	0.031	0.058	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

Figure S97. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S97. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
ITGB1	0.016	0	-9999	-9999
ITGB7	0.016	0	-9999	-9999
ITGA4	0.013	0.022	-9999	-9999
alpha4/beta7 Integrin	0.021	0.014	-9999	-9999
alpha4/beta1 Integrin	0.021	0.014	-9999	-9999

×

Hedgehog signaling events mediated by Gli proteins

Figure S98. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S98. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0	-9999	-10000	0	0
HDAC2	0.016	0	-9999	-10000	0	0
GNB1/GNG2	0.021	0.027	-9999	-10000	0	0
forebrain development	-0.011	0.11	-9999	-0.41	3	3
GNAO1	0.015	0.001	-9999	-10000	0	0
SMO/beta Arrestin2	-0.005	0.028	-9999	-10000	0	0
SMO	-0.004	0.05	-9999	-10000	0	0
ARRB2	0.015	0.001	-9999	-10000	0	0
GLI3/SPOP	-0.095	0.15	-9999	-10000	0	0
mol:GTP	-0.001	0.001	-9999	-10000	0	0
GSK3B	0.016	0	-9999	-10000	0	0
GNAI2	0.015	0.001	-9999	-10000	0	0
SIN3/HDAC complex	0.041	0.001	-9999	-10000	0	0
GNAI1	-0.024	0.16	-9999	-0.69	3	3
XPO1	0.013	0.003	-9999	-10000	0	0
GLI1/Su(fu)	-0.018	0.065	-9999	-10000	0	0
SAP30	0.016	0	-9999	-10000	0	0
mol:GDP	-0.004	0.05	-9999	-10000	0	0
MIM/GLI2A	-0.014	0.098	-9999	-0.7	1	1
IFT88	0.016	0	-9999	-10000	0	0
GNAI3	0.002	0.095	-9999	-0.69	1	1
GLI2	0.047	0.031	-9999	-10000	0	0
GLI3	-0.11	0.16	-9999	-0.27	2	2
CSNK1D	0.013	0.022	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
SAP18	0.016	0	-9999	-10000	0	0
embryonic digit morphogenesis	0.016	0	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
Gi family/GTP	0.008	0.11	-9999	-0.38	3	3
SIN3B	0.016	0	-9999	-10000	0	0
SIN3A	0.016	0	-9999	-10000	0	0
GLI3/Su(fu)	-0.051	0.11	-9999	-10000	0	0
GLI2/Su(fu)	0.06	0.028	-9999	-10000	0	0
FOXA2	-0.08	0.11	-9999	-0.84	1	1
neural tube patterning	-0.011	0.11	-9999	-0.41	3	3
SPOP	0.016	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.032	0.011	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
CSNK1G2	0.016	0	-9999	-10000	0	0
CSNK1G3	0.016	0	-9999	-10000	0	0
MTSS1	-0.014	0.099	-9999	-0.7	1	1
embryonic limb morphogenesis	-0.011	0.11	-9999	-0.41	3	3
SUFU	0.024	0.015	-9999	-10000	0	0
LGALS3	-0.011	0.13	-9999	-0.69	2	2
catabolic process	-0.056	0.14	-9999	-0.34	1	1
GLI3A/CBP	0.002	0.087	-9999	-0.36	3	3
KIF3A	0.016	0	-9999	-10000	0	0
GLI1	-0.011	0.11	-9999	-0.42	3	3
RAB23	0.016	0	-9999	-10000	0	0
CSNK1A1	0.016	0	-9999	-10000	0	0
IFT172	0.016	0	-9999	-10000	0	0
RBBP7	0.007	0.037	-9999	-10000	0	0
Su(fu)/Galectin3	0.016	0.08	-9999	-0.39	2	2
GNAZ	0.015	0.001	-9999	-10000	0	0
RBBP4	0.016	0	-9999	-10000	0	0
CSNK1G1	0.016	0	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GLI2/SPOP	0.052	0.029	-9999	-10000	0	0
STK36	0.01	0.022	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.021	0.1	-9999	-0.64	1	1
PTCH1	0	0.098	-9999	-10000	0	0
MIM/GLI1	-0.037	0.12	-9999	-0.41	4	4
CREBBP	0.002	0.087	-9999	-0.36	3	3
Su(fu)/SIN3/HDAC complex	0.055	0.008	-9999	-10000	0	0

×

Aurora A signaling

Figure S99. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S99. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.004	0.088	-9999	-0.43	2	2
BIRC5	-0.084	0.079	-9999	-10000	0	0
NFKBIA	0.024	0.02	-9999	-10000	0	0
CPEB1	0.013	0.022	-9999	-10000	0	0
AKT1	0.024	0.02	-9999	-10000	0	0
NDEL1	0.016	0	-9999	-10000	0	0
Aurora A/BRCA1	0.019	0.022	-9999	-10000	0	0
NDEL1/TACC3	-0.03	0.035	-9999	-10000	0	0
GADD45A	-0.014	0.13	-9999	-0.69	2	2
GSK3B	0.016	0.001	-9999	-10000	0	0
PAK1/Aurora A	0.022	0.019	-9999	-10000	0	0
MDM2	0.013	0.022	-9999	-10000	0	0
JUB	0.016	0	-9999	-10000	0	0
TPX2	-0.06	0.043	-9999	-10000	0	0
TP53	0.028	0.013	-9999	-10000	0	0
DLG7	-0.05	0.039	-9999	-10000	0	0
AURKAIP1	0.016	0	-9999	-10000	0	0
ARHGEF7	0.016	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.032	0.037	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.018	0.022	-9999	-10000	0	0
AURKA	0.017	0.025	-9999	-10000	0	0
AURKB	0.005	0.016	-9999	-10000	0	0
CDC25B	0.022	0.023	-9999	-10000	0	0
G2/M transition checkpoint	0.02	0.017	-9999	-10000	0	0
mRNA polyadenylation	0.018	0.022	-9999	-10000	0	0
Aurora A/CPEB	0.019	0.022	-9999	-10000	0	0
Aurora A/TACC1/TRAP/chTOG	0.042	0.01	-9999	-10000	0	0
BRCA1	0.013	0.022	-9999	-10000	0	0
centrosome duplication	0.022	0.019	-9999	-10000	0	0
regulation of centrosome cycle	-0.03	0.034	-9999	-10000	0	0
spindle assembly	0.041	0.01	-9999	-10000	0	0
TDRD7	0.016	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	0.017	0.042	-9999	-10000	0	0
CENPA	0.007	0.017	-9999	-10000	0	0
Aurora A/PP2A	0.022	0.019	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	-0.006	0.026	-9999	-10000	0	0
negative regulation of DNA binding	0.027	0.013	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.023	0	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
Ajuba/Aurora A	0.02	0.017	-9999	-10000	0	0
mitotic prometaphase	0.002	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.017	0.025	-9999	-10000	0	0
TACC1	0.016	0	-9999	-10000	0	0
TACC3	-0.12	0.063	-9999	-10000	0	0
Aurora A/Antizyme1	0.034	0.011	-9999	-10000	0	0
Aurora A/RasGAP	0.022	0.019	-9999	-10000	0	0
OAZ1	0.016	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.016	0.001	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.032	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.06	0.043	-9999	-10000	0	0
PPP2R5D	0.016	0	-9999	-10000	0	0
Aurora A/TPX2	-0.031	0.039	-9999	-10000	0	0
PAK1	0.016	0	-9999	-10000	0	0
CKAP5	0.013	0.022	-9999	-10000	0	0

×

Arf6 downstream pathway

Figure S100. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S100. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
PLAUR	0.037	0.037	-9999	-9999
regulation of axonogenesis	-0.03	0.011	-9999	-9999
myoblast fusion	-0.017	0.021	-9999	-9999
mol:GTP	-0.003	0.01	-9999	-9999
regulation of calcium-dependent cell-cell adhesion	-0.037	0.015	-9999	-9999
ARF1/GTP	-0.001	0.004	-9999	-9999
mol:GM1	0.009	0.011	-9999	-9999
mol:Choline	0.03	0.009	-9999	-9999
lamellipodium assembly	-0.004	0.012	-9999	-9999
MAPK3	0.027	0.021	-9999	-9999
ARF6/GTP/NME1/Tiam1	0.038	0.015	-9999	-9999
ARF1	0.016	0	-9999	-9999
ARF6/GDP	0.017	0.021	-9999	-9999
ARF1/GDP	0.026	0.019	-9999	-9999
ARF6	0.013	0.006	-9999	-9999
RAB11A	0.016	0	-9999	-9999
TIAM1	0.017	0.002	-9999	-9999
fibronectin binding	0	0	-9999	-9999
MAPK1	0.027	0.021	-9999	-9999
actin filament bundle formation	-0.025	0.019	-9999	-9999
KALRN	-0.003	0.01	-9999	-9999
RAB11FIP3/RAB11A	0.023	0	-9999	-9999
RhoA/GDP	0.026	0.019	-9999	-9999
NME1	0.017	0.002	-9999	-9999
Rac1/GDP	0.026	0.019	-9999	-9999
substrate adhesion-dependent cell spreading	-0.003	0.01	-9999	-9999
cortical actin cytoskeleton organization	-0.004	0.012	-9999	-9999
RAC1	0.016	0	-9999	-9999
liver development	-0.003	0.01	-9999	-9999
ARF6/GTP	-0.003	0.01	-9999	-9999
RhoA/GTP	-0.001	0.004	-9999	-9999
mol:GDP	-0.004	0.014	-9999	-9999
ARF6/GTP/RAB11FIP3/RAB11A	0.029	0.008	-9999	-9999
RHOA	0.016	0	-9999	-9999
PLD1	0.022	0.011	-9999	-9999
RAB11FIP3	0.016	0	-9999	-9999
tube morphogenesis	-0.004	0.012	-9999	-9999
ruffle organization	0.03	0.011	-9999	-9999
regulation of epithelial cell migration	-0.003	0.01	-9999	-9999
PLD2	0.022	0.011	-9999	-9999
PIP5K1A	0.03	0.011	-9999	-9999
mol:Phosphatidic acid	0.03	0.009	-9999	-9999
Rac1/GTP	-0.004	0.012	-9999	-9999

×

Aurora C signaling

Figure S101. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S101. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
INCENP	0.006	0.037	-9999	-9999
Aurora C/Aurora B/INCENP	0.008	0.035	-9999	-9999
metaphase	0	0	-9999	-9999
mitosis	0	0	-9999	-9999
H3F3B	-0.002	0.003	-9999	-9999
AURKB	-0.021	0.068	-9999	-9999
AURKC	0.016	0	-9999	-9999

×

PLK1 signaling events

Figure S102. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S102. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0	0.018	-9999	-10000	0	0
BUB1B	-0.024	0.026	-9999	-10000	0	0
PLK1	0.011	0.01	-9999	-10000	0	0
PLK1S1	0.006	0.005	-9999	-10000	0	0
KIF2A	0.012	0.056	-9999	-0.39	1	1
regulation of mitotic centrosome separation	0.011	0.01	-9999	-10000	0	0
GOLGA2	0.016	0	-9999	-10000	0	0
Hec1/SPC24	-0.026	0.039	-9999	-10000	0	0
WEE1	0.012	0.016	-9999	-10000	0	0
cytokinesis	-0.019	0.031	-9999	-10000	0	0
PP2A-alpha B56	0.018	0.011	-9999	-10000	0	0
AURKA	0.01	0.011	-9999	-10000	0	0
PICH/PLK1	-0.046	0.075	-9999	-10000	0	0
CENPE	-0.01	0.042	-9999	-10000	0	0
RhoA/GTP	0.012	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.012	0.056	-9999	-0.39	1	1
PPP2CA	0.016	0	-9999	-10000	0	0
FZR1	0.016	0	-9999	-10000	0	0
TPX2	-0.005	0.012	-9999	-10000	0	0
PAK1	0.015	0.001	-9999	-10000	0	0
SPC24	0	0	-9999	-10000	0	0
FBXW11	0.016	0	-9999	-10000	0	0
CLSPN	0.011	0.011	-9999	-10000	0	0
GORASP1	0.016	0	-9999	-10000	0	0
metaphase	0	0.001	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	0.006	0.005	-9999	-10000	0	0
G2 phase of mitotic cell cycle	-0.001	0.001	-9999	-10000	0	0
STAG2	0.016	0	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.012	0.01	-9999	-10000	0	0
spindle elongation	0.011	0.01	-9999	-10000	0	0
ODF2	0.015	0.001	-9999	-10000	0	0
BUB1	-0.007	0.012	-9999	-10000	0	0
TPT1	0.013	0.005	-9999	-10000	0	0
CDC25C	0.001	0.017	-9999	-10000	0	0
CDC25B	-0.003	0.051	-9999	-10000	0	0
SGOL1	0	0.018	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CCNB1/CDK1	-0.006	0.05	-9999	-10000	0	0
CDC14B	0.012	0.001	-9999	-10000	0	0
CDC20	-0.09	0.078	-9999	-10000	0	0
PLK1/PBIP1	0	0.032	-9999	-10000	0	0
mitosis	0	0.002	-9999	-10000	0	0
FBXO5	0.011	0.018	-9999	-10000	0	0
CDC2	-0.045	0.079	-9999	-10000	0	0
NDC80	-0.087	0.079	-9999	-10000	0	0
metaphase plate congression	0.013	0.006	-9999	-10000	0	0
ERCC6L	-0.041	0.07	-9999	-10000	0	0
NLP/gamma Tubulin	0.011	0.005	-9999	-10000	0	0
microtubule cytoskeleton organization	0.012	0.005	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-9999	-10000	0	0
PPP1R12A	0.015	0	-9999	-10000	0	0
interphase	0	0.001	-9999	-10000	0	0
PLK1/PRC1-2	-0.057	0.058	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	0.034	0.006	-9999	-10000	0	0
RAB1A	0.016	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	0.015	0.011	-9999	-10000	0	0
mitotic prometaphase	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.012	-9999	-10000	0	0
microtubule-based process	-0.04	0.035	-9999	-10000	0	0
Golgi organization	0.011	0.01	-9999	-10000	0	0
Cohesin/SA2	0.008	0.008	-9999	-10000	0	0
PPP1CB/MYPT1	0.022	0.001	-9999	-10000	0	0
KIF20A	-0.11	0.066	-9999	-10000	0	0
APC/C/CDC20	-0.029	0.04	-9999	-10000	0	0
PPP2R1A	0.016	0	-9999	-10000	0	0
chromosome segregation	-0.001	0.031	-9999	-10000	0	0
PRC1	-0.051	0.08	-9999	-10000	0	0
ECT2	0.005	0.034	-9999	-10000	0	0
C13orf34	0.016	0.009	-9999	-10000	0	0
NUDC	0.013	0.006	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.024	0.026	-9999	-10000	0	0
spindle assembly	0.013	0.008	-9999	-10000	0	0
spindle stabilization	0.006	0.005	-9999	-10000	0	0
APC/C/HCDH1	0.021	0	-9999	-10000	0	0
MKLP2/PLK1	-0.04	0.035	-9999	-10000	0	0
CCNB1	-0.048	0.08	-9999	-10000	0	0
PPP1CB	0.015	0	-9999	-10000	0	0
BTRC	0.016	0	-9999	-10000	0	0
ROCK2	0.022	0.007	-9999	-10000	0	0
TUBG1	0.013	0.005	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.028	0.035	-9999	-10000	0	0
MLF1IP	-0.013	0.047	-9999	-10000	0	0
INCENP	0.005	0.037	-9999	-10000	0	0

×

Insulin-mediated glucose transport

Figure S103. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S103. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.012	0.098	-9999	-10000	0	0
CaM/Ca2+	0.012	0	-9999	-10000	0	0
AKT1	0.016	0	-9999	-10000	0	0
AKT2	0.016	0	-9999	-10000	0	0
STXBP4	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	0.009	0.11	-9999	-0.21	10	10
YWHAZ	0.016	0	-9999	-10000	0	0
CALM1	0.016	0	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
TBC1D4	-0.074	0.21	-9999	-0.51	10	10
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0.016	0	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
SNARE/Synip	0.032	0	-9999	-10000	0	0
YWHAG	0.016	0	-9999	-10000	0	0
ASIP	0	0	-9999	-10000	0	0
PRKCI	0.013	0.022	-9999	-10000	0	0
AS160/CaM/Ca2+	0.012	0	-9999	-10000	0	0
RHOQ	0.016	0	-9999	-10000	0	0
GYS1	0.035	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
TRIP10	0.013	0.022	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.02	0.012	-9999	-10000	0	0
AS160/14-3-3	0.01	0.083	-9999	-10000	0	0
VAMP2	0.016	0	-9999	-10000	0	0
SLC2A4	0.007	0.12	-9999	-0.23	10	10
STX4	0.016	0	-9999	-10000	0	0
GSK3B	0.029	0	-9999	-10000	0	0
SFN	-0.012	0.061	-9999	-10000	0	0
LNPEP	0.016	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

Figure S104. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S104. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.026	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.037	0.011	-10000	0	-10000	0	0
CDKN1B	0.018	0.1	-10000	0	-0.34	4	4
CDKN1A	0.046	0.004	-10000	0	-10000	0	0
FRAP1	0.016	0	-10000	0	-10000	0	0
PRKDC	0.013	0.022	-10000	0	-10000	0	0
FOXO3	0.046	0.004	-10000	0	-10000	0	0
AKT1	0	0.001	-10000	0	-10000	0	0
BAD	0.013	0.022	-10000	0	-10000	0	0
AKT3	0.02	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.046	0.004	-10000	0	-10000	0	0
AKT1/ASK1	0.03	0.07	-10000	0	-0.33	2	2
BAD/YWHAZ	0.03	0.012	-10000	0	-10000	0	0
RICTOR	0.016	0	-10000	0	-10000	0	0
RAF1	0.013	0.022	-10000	0	-10000	0	0
JNK cascade	0.012	0.06	0.32	2	-10000	0	2
TSC1	0.046	0.004	-10000	0	-10000	0	0
YWHAZ	0.016	0	-10000	0	-10000	0	0
AKT1/RAF1	0.046	0.005	-10000	0	-10000	0	0
EP300	0.016	0	-10000	0	-10000	0	0
mol:GDP	0.039	0.005	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.046	0.004	-10000	0	-10000	0	0
YWHAQ	0.016	0	-10000	0	-10000	0	0
TBC1D4	-0.058	0.18	-10000	0	-0.43	10	10
MAP3K5	-0.011	0.13	-10000	0	-0.69	2	2
MAPKAP1	0.016	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.048	0.009	-10000	0	-10000	0	0
YWHAH	0.016	0	-10000	0	-10000	0	0
AKT1S1	0.046	0.004	-10000	0	-10000	0	0
CASP9	0.046	0.004	-10000	0	-10000	0	0
YWHAB	0.016	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.026	0.097	-10000	0	-0.32	4	4
GBL	0.016	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.032	0	-10000	0	-10000	0	0
YWHAE	0.016	0	-10000	0	-10000	0	0
SRC	0.016	0	-10000	0	-10000	0	0
AKT2/p21CIP1	0	0.002	-10000	0	-10000	0	0
KIAA1303	0.016	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.043	0.003	-10000	0	-10000	0	0
CHUK	0.046	0.004	-10000	0	-10000	0	0
BAD/BCL-XL	0.061	0.004	-10000	0	-10000	0	0
mTORC2	0.04	0	-10000	0	-10000	0	0
AKT2	0.02	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.067	0.009	-10000	0	-10000	0	0
PDPK1	0.016	0	-10000	0	-10000	0	0
MDM2	0.045	0.01	-10000	0	-10000	0	0
MAPKKK cascade	-0.046	0.005	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.059	0.009	-10000	0	-10000	0	0
TSC1/TSC2	0.053	0.004	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.056	0.009	-10000	0	-10000	0	0
glucose import	-0.13	0.22	-10000	0	-0.4	20	20
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.054	0.004	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.13	0.22	-10000	0	-0.41	20	20
GSK3A	0.046	0.004	-10000	0	-10000	0	0
FOXO1	0.046	0.004	-10000	0	-10000	0	0
GSK3B	0.046	0.004	-10000	0	-10000	0	0
SFN	-0.012	0.061	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.053	0.004	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.047	0.021	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
KPNA1	0.016	0	-10000	0	-10000	0	0
HSP90AA1	0.016	0	-10000	0	-10000	0	0
YWHAG	0.016	0	-10000	0	-10000	0	0
RHEB	0.013	0.022	-10000	0	-10000	0	0
CREBBP	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

Figure S105. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S105. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.016	0	-9999	-10000	0	0
HDAC4	0.013	0.022	-9999	-10000	0	0
induction of apoptosis	0	0	-9999	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.01	0	-9999	-10000	0	0
CDKN1A	0	0	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
BAX	0.006	0.037	-9999	-10000	0	0
FOXO3	0	0	-9999	-10000	0	0
FOXO1	0.016	0	-9999	-10000	0	0
FOXO4	0.026	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
XRCC6	0.016	0	-9999	-10000	0	0
TAT	0.016	0	-9999	-10000	0	0
mol:Lysophosphatidic acid	0	0	-9999	-10000	0	0
MYOD1	0.007	0.025	-9999	-10000	0	0
PPARGC1A	0.013	0.022	-9999	-10000	0	0
FHL2	-0.024	0.16	-9999	-0.69	3	3
response to nutrient levels	0	0	-9999	-10000	0	0
KU70/SIRT1	0	0	-9999	-10000	0	0
HIST2H4A	0.01	0	-9999	-10000	0	0
SIRT1/FOXO3a	0	0	-9999	-10000	0	0
SIRT1	0.01	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
SIRT1/MEF2D/HDAC4	-0.001	0.008	-9999	-10000	0	0
SIRT1/Histone H1b	0.024	0.007	-9999	-10000	0	0
apoptosis	0.003	0.013	-9999	-10000	0	0
SIRT1/PGC1A	-0.001	0.009	-9999	-10000	0	0
p53/SIRT1	0	0	-9999	-10000	0	0
SIRT1/FOXO4	0.025	0	-9999	-10000	0	0
FOXO1/FHL2/SIRT1	0.003	0.098	-9999	-0.4	3	3
HIST1H1E	0.024	0.009	-9999	-10000	0	0
SIRT1/p300	0	0	-9999	-10000	0	0
muscle cell differentiation	0.004	0.015	-9999	-10000	0	0
TP53	0.01	0	-9999	-10000	0	0
KU70/SIRT1/BAX	-0.003	0.013	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
MEF2D	0.016	0	-9999	-10000	0	0
HIV-1 Tat/SIRT1	0	0	-9999	-10000	0	0
ACSS2	0.022	0	-9999	-10000	0	0
SIRT1/PCAF/MYOD	-0.004	0.015	-9999	-10000	0	0

×

Reelin signaling pathway

Figure S106. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S106. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.023	0	-9999	-10000	0	0
VLDLR	0.016	0	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
LRPAP1	0.016	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
ITGA3	0.016	0	-9999	-10000	0	0
RELN/VLDLR/Fyn	0.029	0.016	-9999	-10000	0	0
MAPK8IP1/MKK7/MAP3K11/JNK1	0.046	0.002	-9999	-10000	0	0
AKT1	0.03	0.079	-9999	-0.54	1	1
MAP2K7	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
DAB1	0.016	0	-9999	-10000	0	0
RELN/LRP8/DAB1	-0.005	0.042	-9999	-10000	0	0
LRPAP1/LRP8	-0.019	0.051	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	0.004	0.039	-9999	-10000	0	0
DAB1/alpha3/beta1 Integrin	0.01	0.018	-9999	-10000	0	0
long-term memory	0.035	0.055	-9999	-0.34	1	1
DAB1/LIS1	0.012	0.021	-9999	-10000	0	0
DAB1/CRLK/C3G	0.01	0.018	-9999	-10000	0	0
PIK3CA	0.002	0.095	-9999	-0.69	1	1
DAB1/NCK2	0.013	0.022	-9999	-10000	0	0
ARHGEF2	0.016	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	0.016	0	-9999	-10000	0	0
CDK5R1	0.016	0	-9999	-10000	0	0
RELN	0.01	0.031	-9999	-10000	0	0
PIK3R1	0.002	0.095	-9999	-0.69	1	1
RELN/LRP8/Fyn	-0.007	0.046	-9999	-10000	0	0
GRIN2A/RELN/LRP8/DAB1/Fyn	0.038	0.02	-9999	-10000	0	0
MAPK8	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	0.027	0.015	-9999	-10000	0	0
ITGB1	0.016	0	-9999	-10000	0	0
MAP1B	-0.022	0.12	-9999	-0.37	5	5
RELN/LRP8	-0.007	0.046	-9999	-10000	0	0
GRIN2B/RELN/LRP8/DAB1/Fyn	0.03	0.057	-9999	-0.36	1	1
PI3K	0.005	0.13	-9999	-0.94	1	1
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.023	0	-9999	-10000	0	0
RAP1A	0.015	0.094	-9999	-0.37	2	2
PAFAH1B1	0.016	0	-9999	-10000	0	0
MAPK8IP1	0.013	0.022	-9999	-10000	0	0
CRLK/C3G	0.023	0	-9999	-10000	0	0
GRIN2B	-0.001	0.097	-9999	-0.69	1	1
NCK2	0.016	0	-9999	-10000	0	0
neuron differentiation	0.037	0.018	-9999	-10000	0	0
neuron adhesion	0.03	0.089	-9999	-10000	0	0
LRP8	-0.051	0.08	-9999	-10000	0	0
GSK3B	0.037	0.075	-9999	-0.51	1	1
RELN/VLDLR/DAB1/Fyn	0.034	0.014	-9999	-10000	0	0
MAP3K11	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	0.023	0.083	-9999	-0.58	1	1
CDK5	0.016	0	-9999	-10000	0	0
MAPT	-0.022	0.12	-9999	-0.65	2	2
neuron migration	0.047	0.05	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.037	0.018	-9999	-10000	0	0
RELN/VLDLR	0.005	0.042	-9999	-10000	0	0

×

S1P5 pathway

Figure S107. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S107. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.017	0.091	0.56	1	-10000	0	1
GNAI2	0.016	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.011	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.016	0	-10000	0	-10000	0	0
RhoA/GTP	0.017	0.093	-10000	0	-0.57	1	1
negative regulation of cAMP metabolic process	0.011	0.1	-10000	0	-0.36	3	3
GNAZ	0.016	0	-10000	0	-10000	0	0
GNAI3	0.002	0.095	-10000	0	-0.69	1	1
GNA12	0.016	0	-10000	0	-10000	0	0
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.01	0.1	-10000	0	-0.37	3	3
RhoA/GDP	0.012	0	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
GNAI1	-0.024	0.16	-10000	0	-0.69	3	3

×

HIF-2-alpha transcription factor network

Figure S108. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S108. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0.005	0.019	-10000	0	-10000	0	0
oxygen homeostasis	0.01	0.012	-10000	0	-10000	0	0
TCEB2	0.016	0	-10000	0	-10000	0	0
TCEB1	0.016	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.01	0.082	-10000	0	-0.38	1	1
EPO	0.13	0.16	-10000	0	-0.47	1	1
FIH (dimer)	0.025	0.011	-10000	0	-10000	0	0
APEX1	0.026	0.011	-10000	0	-10000	0	0
SERPINE1	0.12	0.18	-10000	0	-0.54	1	1
FLT1	-0.014	0.16	-10000	0	-1.2	1	1
ADORA2A	0.11	0.17	-10000	0	-0.53	1	1
germ cell development	0.12	0.18	-10000	0	-0.52	1	1
SLC11A2	0.12	0.18	-10000	0	-0.54	1	1
BHLHE40	0.11	0.18	-10000	0	-0.55	1	1
HIF1AN	0.025	0.011	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.092	0.14	-10000	0	-0.46	1	1
ETS1	0.033	0.005	-10000	0	-10000	0	0
CITED2	-0.014	0.14	-10000	0	-1	1	1
KDR	0.005	0.03	-10000	0	-10000	0	0
PGK1	0.12	0.18	-10000	0	-0.54	1	1
SIRT1	0.016	0	-10000	0	-10000	0	0
response to hypoxia	0.001	0	-10000	0	-10000	0	0
HIF2A/ARNT	0.15	0.2	-10000	0	-0.63	1	1
EPAS1	0.051	0.13	-10000	0	-0.34	3	3
SP1	0.023	0.006	-10000	0	-10000	0	0
ABCG2	0.082	0.28	-10000	0	-0.7	5	5
EFNA1	0.12	0.18	-10000	0	-0.54	1	1
FXN	0.12	0.17	-10000	0	-0.53	1	1
POU5F1	0.12	0.18	-10000	0	-0.54	1	1
neuron apoptosis	-0.14	0.2	0.61	1	-10000	0	1
EP300	0.016	0	-10000	0	-10000	0	0
EGLN3	-0.014	0.071	-10000	0	-10000	0	0
EGLN2	0.025	0.011	-10000	0	-10000	0	0
EGLN1	0.025	0.011	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.032	0	-10000	0	-10000	0	0
VHL	0.016	0	-10000	0	-10000	0	0
ARNT	0.026	0.011	-10000	0	-10000	0	0
SLC2A1	0.1	0.19	-10000	0	-0.58	1	1
TWIST1	0.12	0.17	-10000	0	-0.53	1	1
ELK1	0.023	0.014	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.092	0.14	-10000	0	-0.45	1	1
VEGFA	0.1	0.19	-10000	0	-0.6	1	1
CREBBP	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

Figure S109. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S109. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.006	0.054	-9999	-0.4	1	1
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.045	0.054	-9999	-0.34	1	1
SUMO1	0.016	0	-9999	-10000	0	0
ZFPM1	0.016	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.025	0	-9999	-10000	0	0
FKBP3	0.016	0	-9999	-10000	0	0
Histones	0.048	0.03	-9999	-10000	0	0
YY1/LSF	0.022	0.061	-9999	-0.42	1	1
SMG5	0.016	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.03	0.047	-9999	-0.3	1	1
I kappa B alpha/HDAC1	0.032	0.033	-9999	-10000	0	0
SAP18	0.016	0	-9999	-10000	0	0
RELA	0.035	0.043	-9999	-0.27	1	1
HDAC1/Smad7	0.032	0	-9999	-10000	0	0
RANGAP1	0.016	0	-9999	-10000	0	0
HDAC3/TR2	0.032	0.033	-9999	-10000	0	0
NuRD/MBD3 Complex	0.047	0.013	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.04	0.039	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.012	0.061	-9999	-10000	0	0
GATA1	0.016	0	-9999	-10000	0	0
Mad/Max	0.023	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.059	0.013	-9999	-10000	0	0
RBBP7	0.006	0.037	-9999	-10000	0	0
NPC	0.009	0	-9999	-10000	0	0
RBBP4	0.016	0	-9999	-10000	0	0
MAX	0.016	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.016	0	-9999	-10000	0	0
NFKBIA	0.025	0.037	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.048	0.007	-9999	-10000	0	0
SIN3 complex	0.04	0	-9999	-10000	0	0
SMURF1	0.016	0	-9999	-10000	0	0
CHD3	0.006	0.037	-9999	-10000	0	0
SAP30	0.016	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.016	0	-9999	-10000	0	0
YY1/HDAC3	0.039	0.031	-9999	-10000	0	0
YY1/HDAC2	0.03	0	-9999	-10000	0	0
YY1/HDAC1	0.03	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.047	0.013	-9999	-10000	0	0
PPARG	-0.23	0.18	-9999	-0.33	39	39
HDAC8/hEST1B	0.032	0	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
TNFRSF1A	0.002	0.095	-9999	-0.69	1	1
HDAC3/SMRT (N-CoR2)	0.032	0.033	-9999	-10000	0	0
MBD3L2	0.012	0.022	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.031	0	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.055	0.015	-9999	-10000	0	0
HDAC1	0.016	0	-9999	-10000	0	0
HDAC3	0.025	0.037	-9999	-10000	0	0
HDAC2	0.016	0	-9999	-10000	0	0
YY1	0.026	0	-9999	-10000	0	0
HDAC8	0.016	0	-9999	-10000	0	0
SMAD7	0.016	0	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
MXD1	0.016	0	-9999	-10000	0	0
STAT3	0.029	0	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.016	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.03	0.057	-9999	-0.38	1	1
YY1/SAP30/HDAC1	0.038	0	-9999	-10000	0	0
EP300	0.016	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.029	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.037	-9999	-10000	0	0
histone deacetylation	0.047	0.013	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.041	0.031	-9999	-10000	0	0
nuclear export	-0.031	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GATAD2B	0.016	0	-9999	-10000	0	0
GATAD2A	0.003	0.043	-9999	-10000	0	0
GATA2/HDAC3	0.019	0.042	-9999	-10000	0	0
GATA1/HDAC1	0.023	0	-9999	-10000	0	0
GATA1/HDAC3	0.032	0.033	-9999	-10000	0	0
CHD4	0.016	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	0.007	0.075	-9999	-0.51	1	1
SIN3/HDAC complex/Mad/Max	0.053	0.006	-9999	-10000	0	0
NuRD Complex	0.056	0.014	-9999	-10000	0	0
positive regulation of chromatin silencing	0.045	0.03	-9999	-10000	0	0
SIN3B	0.016	0	-9999	-10000	0	0
MTA2	0.006	0.037	-9999	-10000	0	0
SIN3A	0.016	0	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
SUMO1/HDAC1	0.035	0	-9999	-10000	0	0
HDAC complex	0.036	0.018	-9999	-10000	0	0
GATA1/Fog1	0.023	0	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0.032	0	-9999	-10000	0	0
TNF	0.006	0.037	-9999	-10000	0	0
negative regulation of cell growth	0.052	0.006	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.047	0.013	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.038	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.038	0.056	-9999	-0.36	1	1
SIN3/HDAC complex/NCoR1	0.05	0.006	-9999	-10000	0	0
TFCP2	0.002	0.095	-9999	-0.69	1	1
NR2C1	0.016	0	-9999	-10000	0	0
MBD3	0.016	0	-9999	-10000	0	0
MBD2	0.016	0	-9999	-10000	0	0

×

TCGA08_p53

Figure S110. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S110. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
CDKN2A	-0.031	0.053	-9999	-9999
TP53	-0.011	0.019	-9999	-9999
Senescence	-0.011	0.018	-9999	-9999
Apoptosis	-0.011	0.018	-9999	-9999
Activated_Oncogenes	0	0	-9999	-9999
MDM2	0.023	0.032	-9999	-9999
MDM4	0.013	0.022	-9999	-9999

×

Signaling mediated by p38-gamma and p38-delta

Figure S111. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S111. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.033	0	-9999	-10000	0	0
SNTA1	0.016	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.011	0.038	-9999	-10000	0	0
MAPK12	0.017	0.031	-9999	-10000	0	0
CCND1	0.017	0.015	-9999	-10000	0	0
p38 gamma/SNTA1	0.025	0.029	-9999	-10000	0	0
MAP2K3	0.016	0	-9999	-10000	0	0
PKN1	0.013	0.022	-9999	-10000	0	0
G2/M transition checkpoint	0.017	0.031	-9999	-10000	0	0
MAP2K6	0.014	0.03	-9999	-10000	0	0
MAPT	0.016	0.071	-9999	-0.34	2	2
MAPK13	0.026	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.019	0.008	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

Figure S112. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S112. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0	-10000	0	-10000	0	0
HDAC3	0.016	0	-10000	0	-10000	0	0
VDR	-0.011	0.13	-10000	0	-0.69	2	2
Cbp/p300/PCAF	0.021	0	-10000	0	-10000	0	0
EP300	0.016	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.046	0.013	-10000	0	-10000	0	0
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.016	0	-10000	0	-10000	0	0
AKT1	0.041	0.038	0.23	1	-10000	0	1
RAR alpha/9cRA/Cyclin H	-0.015	0.046	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.041	0.016	-10000	0	-10000	0	0
CDC2	-0.045	0.079	-10000	0	-10000	0	0
response to UV	-0.001	0.007	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.023	0.022	-10000	0	-10000	0	0
NCOR2	0.016	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.008	0.1	-10000	0	-0.52	2	2
RXRs/RARs/NRIP1/9cRA	0.029	0.15	-10000	0	-0.5	4	4
NCOA2	0.016	0	-10000	0	-10000	0	0
NCOA3	0.016	0	-10000	0	-10000	0	0
NCOA1	0.016	0	-10000	0	-10000	0	0
VDR/VDR/DNA	-0.011	0.13	-10000	0	-0.69	2	2
RARG	0.016	0.004	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.02	0.006	-10000	0	-10000	0	0
MAPK3	0.015	0.004	-10000	0	-10000	0	0
MAPK1	0.016	0	-10000	0	-10000	0	0
MAPK8	0.016	0.004	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.024	0.1	-10000	0	-0.33	2	2
RARA	0.028	0.026	-10000	0	-10000	0	0
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.041	0.016	-10000	0	-10000	0	0
PRKCA	0.016	0.014	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.015	0.16	-10000	0	-0.56	4	4
RXRG	0.028	0.026	-10000	0	-10000	0	0
RXRA	0.017	0.066	-10000	0	-0.27	1	1
RXRB	0.028	0.025	-10000	0	-10000	0	0
VDR/Vit D3/DNA	-0.008	0.1	-10000	0	-0.52	2	2
RBP1	-0.064	0.12	-10000	0	-0.69	1	1
CRBP1/9-cic-RA	-0.041	0.084	-10000	0	-0.52	1	1
RARB	0.017	0.005	-10000	0	-10000	0	0
PRKCG	0.016	0.014	-10000	0	-10000	0	0
MNAT1	0.016	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.041	0.11	-10000	0	-0.34	1	1
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.049	0.076	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.046	0.027	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	0.015	0.16	-10000	0	-0.56	4	4
positive regulation of DNA binding	-0.014	0.044	-10000	0	-10000	0	0
NRIP1	-0.028	0.32	-10000	0	-1.1	4	4
RXRs/RARs	0.022	0.12	-10000	0	-0.4	4	4
RXRs/RXRs/DNA/9cRA	-0.015	0.085	-10000	0	-0.31	2	2
PRKACA	0.016	0	-10000	0	-10000	0	0
CDK7	0.016	0	-10000	0	-10000	0	0
TFIIH	0.032	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.001	0.003	-10000	0	-10000	0	0
CCNH	0.016	0	-10000	0	-10000	0	0
CREBBP	0.016	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

Figure S113. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S113. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.016	0	-9999	-10000	0	0
Rac1/GDP	0	0.003	-9999	-10000	0	0
DOCK1	0.016	0	-9999	-10000	0	0
ITGA4	0.013	0.022	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
alpha4/beta7 Integrin	0.021	0.014	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.03	0.012	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.037	0.011	-9999	-10000	0	0
lamellipodium assembly	-0.01	0.085	-9999	-0.62	1	1
PIK3CA	0.002	0.095	-9999	-0.69	1	1
PI3K	0.005	0.13	-9999	-0.94	1	1
ARF6	0.016	0	-9999	-10000	0	0
TLN1	0.016	0	-9999	-10000	0	0
PXN	0.026	0	-9999	-10000	0	0
PIK3R1	0.002	0.095	-9999	-0.69	1	1
ARF6/GTP	0.001	0.004	-9999	-10000	0	0
cell adhesion	0.045	0.002	-9999	-10000	0	0
CRKL/CBL	0.023	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.037	0.011	-9999	-10000	0	0
ITGB1	0.016	0	-9999	-10000	0	0
ITGB7	0.016	0	-9999	-10000	0	0
ARF6/GDP	0	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.067	0.18	-9999	-0.36	15	15
p130Cas/Crk/Dock1	0.032	0	-9999	-10000	0	0
VCAM1	-0.18	0.32	-9999	-0.69	15	15
alpha4/beta1 Integrin/Paxillin/Talin	0.046	0.002	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.046	0.002	-9999	-10000	0	0
BCAR1	0.016	0	-9999	-10000	0	0
mol:GDP	-0.045	0.002	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.046	0.002	-9999	-10000	0	0
Rac1/GTP	-0.012	0.098	-9999	-0.72	1	1

×

Atypical NF-kappaB pathway

Figure S114. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S114. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.023	0	-9999	-10000	0	0
FBXW11	0.016	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.022	0.063	-9999	-0.44	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.051	0.009	-9999	-10000	0	0
NFKBIA	0.029	0.011	-9999	-10000	0	0
MAPK14	0.016	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.031	0	-9999	-10000	0	0
ARRB2	0.02	0	-9999	-10000	0	0
REL	0.002	0.095	-9999	-0.69	1	1
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.031	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.031	0	-9999	-10000	0	0
PIK3CA	0.002	0.095	-9999	-0.69	1	1
NF kappa B1 p50 dimer	0.023	0	-9999	-10000	0	0
PIK3R1	0.002	0.095	-9999	-0.69	1	1
NFKB1	0.026	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.037	0.01	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.055	0.009	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PI3K	0.005	0.13	-9999	-0.94	1	1
NF kappa B1 p50/RelA	0.037	0.01	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
SYK	0.003	0.043	-9999	-10000	0	0
I kappa B alpha/PIK3R1	0.029	0.054	-9999	-0.36	1	1
cell death	0.053	0.009	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.022	0.063	-9999	-0.44	1	1
LCK	0.01	0.031	-9999	-10000	0	0
BCL3	0.016	0	-9999	-10000	0	0

×

Canonical Wnt signaling pathway

Figure S115. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S115. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0.003	-10000	0	-10000	0	0
AES	0.011	0.003	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.024	0	-10000	0	-10000	0	0
SMAD4	0.016	0	-10000	0	-10000	0	0
DKK2	0.002	0.095	-10000	0	-0.69	1	1
TLE1	-0.001	0.043	-10000	0	-10000	0	0
MACF1	0.016	0	-10000	0	-10000	0	0
CTNNB1	0.058	0.054	-10000	0	-10000	0	0
WIF1	-0.082	0.24	-10000	0	-0.69	7	7
beta catenin/RanBP3	0.003	0.019	-10000	0	-10000	0	0
KREMEN2	-0.06	0.081	-10000	0	-10000	0	0
DKK1	-0.033	0.074	-10000	0	-10000	0	0
beta catenin/beta TrCP1	0.064	0.051	-10000	0	-10000	0	0
FZD1	0.016	0	-10000	0	-10000	0	0
AXIN2	0.014	0.038	-10000	0	-10000	0	0
AXIN1	0.016	0	-10000	0	-10000	0	0
RAN	0.015	0	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.011	0.028	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.057	0.04	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.022	0.029	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.067	0.019	-10000	0	-10000	0	0
HNF1A	-0.013	0.058	-10000	0	-10000	0	0
CTBP1	0.011	0.003	-10000	0	-10000	0	0
MYC	0.025	0.011	-10000	0	-10000	0	0
RANBP3	0.015	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.017	0.08	-10000	0	-0.51	1	1
NKD1	-0.039	0.077	-10000	0	-10000	0	0
TCF4	0.011	0.003	-10000	0	-10000	0	0
TCF3	-0.001	0.042	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.041	0.002	-10000	0	-10000	0	0
Ran/GTP	0.011	0	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.01	0.028	-10000	0	-10000	0	0
LEF1	-0.08	0.08	-10000	0	-10000	0	0
DVL1	0.047	0.032	-10000	0	-10000	0	0
CSNK2A1	0.016	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.071	0.042	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.033	0.059	-10000	0	-10000	0	0
LRP6	0.016	0	-10000	0	-10000	0	0
CSNK1A1	0.011	0.003	-10000	0	-10000	0	0
NLK	0.013	0.022	-10000	0	-10000	0	0
CCND1	0.023	0.019	-10000	0	-10000	0	0
WNT1	0.016	0	-10000	0	-10000	0	0
GSK3A	0.016	0	-10000	0	-10000	0	0
GSK3B	0.016	0	-10000	0	-10000	0	0
FRAT1	0.015	0	-10000	0	-10000	0	0
PPP2R5D	0.048	0.034	-10000	0	-10000	0	0
APC	0.045	0.002	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.037	0.087	0.26	7	-10000	0	7
CREBBP	0.011	0.003	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

Figure S116. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S116. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.013	0	-9999	-10000	0	0
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.023	0	-9999	-10000	0	0
STXBP1	0.016	0	-9999	-10000	0	0
ACh/CHRNA1	0.016	0.015	-9999	-10000	0	0
RAB3GAP2/RIMS1/UNC13B	0.032	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	0.016	0	-9999	-10000	0	0
mol:ACh	0.008	0.02	-9999	-0.14	1	1
RAB3GAP2	0.016	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.002	0.021	-9999	-10000	0	0
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	0.016	0.015	-9999	-10000	0	0
UNC13B	0.016	0	-9999	-10000	0	0
CHRNA1	0.016	0	-9999	-10000	0	0
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	0.009	0.028	-9999	-10000	0	0
SNAP25	0.001	0.047	-9999	-0.34	1	1
VAMP2	0.008	0	-9999	-10000	0	0
SYT1	0.003	0.043	-9999	-10000	0	0
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.021	0	-9999	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	-0.002	0.021	-9999	-10000	0	0

×

Glypican 2 network

Figure S117. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S117. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
MDK	-0.042	0.078	-9999	-9999
GPC2	0	0	-9999	-9999
GPC2/Midkine	-0.026	0.05	-9999	-9999
neuron projection morphogenesis	-0.026	0.05	-9999	-9999

×

Wnt signaling

Figure S118. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S118. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	0.017	0.064	-9999	-10000	0	0
FZD6	0.002	0.095	-9999	-0.69	1	1
WNT6	0.003	0.043	-9999	-10000	0	0
WNT4	0.002	0.095	-9999	-0.69	1	1
FZD3	0.006	0.037	-9999	-10000	0	0
WNT5A	-0.015	0.063	-9999	-10000	0	0
WNT11	0.01	0.031	-9999	-10000	0	0

×

TCGA08_rtk_signaling

Figure S119. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S119. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.05	0.2	-10000	0	-0.69	5	5
HRAS	0.016	0	-10000	0	-10000	0	0
EGFR	-0.066	0.22	-10000	0	-0.69	6	6
AKT	0.044	0.029	-10000	0	-10000	0	0
FOXO3	0.016	0	-10000	0	-10000	0	0
AKT1	0.016	0	-10000	0	-10000	0	0
FOXO1	0.016	0	-10000	0	-10000	0	0
AKT3	0.016	0	-10000	0	-10000	0	0
FOXO4	0.016	0	-10000	0	-10000	0	0
MET	0.013	0.022	-10000	0	-10000	0	0
PIK3CA	0.002	0.095	-10000	0	-0.69	1	1
PIK3CB	0.016	0	-10000	0	-10000	0	0
NRAS	0.013	0.022	-10000	0	-10000	0	0
PIK3CG	0.016	0	-10000	0	-10000	0	0
PIK3R3	0	0.047	-10000	0	-10000	0	0
PIK3R2	0.016	0	-10000	0	-10000	0	0
NF1	0.016	0	-10000	0	-10000	0	0
RAS	-0.009	0.088	-10000	0	-0.26	3	3
ERBB2	0.01	0.031	-10000	0	-10000	0	0
proliferation/survival/translation	-0.039	0.033	0.16	1	-10000	0	1
PI3K	0.002	0.099	0.21	1	-0.26	4	5
PIK3R1	0.002	0.095	-10000	0	-0.69	1	1
KRAS	0.016	0	-10000	0	-10000	0	0
FOXO	0.052	0.031	-10000	0	-10000	0	0
AKT2	0.016	0	-10000	0	-10000	0	0
PTEN	0.002	0.095	-10000	0	-0.69	1	1

×

E-cadherin signaling in the nascent adherens junction

Figure S120. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S120. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.032	0.076	-9999	-0.48	1	1
KLHL20	-0.004	0.019	-9999	-10000	0	0
CYFIP2	0.013	0.022	-9999	-10000	0	0
Rac1/GDP	0.052	0.064	-9999	-0.29	1	1
ENAH	0.032	0.076	-9999	-0.48	1	1
AP1M1	0.016	0	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
RAP1A	-0.024	0.16	-9999	-0.69	3	3
CTNNB1	0.016	0	-9999	-10000	0	0
CDC42/GTP	-0.018	0.063	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.002	0.012	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.032	0.058	-9999	-0.39	1	1
RAPGEF1	0.045	0.067	-9999	-0.41	1	1
CTNND1	0.016	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.024	0.077	-9999	-0.51	1	1
CRK	0.039	0.071	-9999	-0.45	1	1
E-cadherin/gamma catenin/alpha catenin	0.023	0.063	-9999	-0.44	1	1
alphaE/beta7 Integrin	0.023	0	-9999	-10000	0	0
IQGAP1	0.016	0	-9999	-10000	0	0
NCKAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.006	0.098	-9999	-0.4	3	3
DLG1	0.032	0.076	-9999	-0.48	1	1
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.016	0.063	-9999	-0.38	1	1
MLLT4	0.016	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.03	0	-9999	-10000	0	0
PI3K	-0.021	0.085	-9999	-0.54	1	1
ARF6	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0.013	0.072	-9999	-0.51	1	1
TIAM1	0.016	0	-9999	-10000	0	0
E-cadherin(dimer)/Ca2+	0.03	0.055	-9999	-0.37	1	1
AKT1	-0.011	0.044	-9999	-0.27	1	1
PIK3R1	0.002	0.095	-9999	-0.69	1	1
CDH1	0.003	0.095	-9999	-0.69	1	1
RhoA/GDP	0.051	0.064	-9999	-0.29	1	1
actin cytoskeleton organization	0.045	0.026	-9999	-10000	0	0
CDC42/GDP	0.051	0.064	-9999	-0.29	1	1
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.023	0.043	-9999	-0.29	1	1
ITGB7	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.033	0.058	-9999	-0.39	1	1
E-cadherin/Ca2+/beta catenin/alpha catenin	0.021	0.055	-9999	-0.38	1	1
mol:GDP	0.046	0.072	-9999	-0.34	1	1
CDC42/GTP/IQGAP1	0.021	0	-9999	-10000	0	0
JUP	0.016	0	-9999	-10000	0	0
p120 catenin/RhoA/GDP	0.05	0.064	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0.021	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.023	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.036	0.021	-9999	-10000	0	0
NME1	0.016	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.032	0.076	-9999	-0.48	1	1
regulation of cell-cell adhesion	-0.016	0.055	-9999	-10000	0	0
WASF2	0	0.007	-9999	-10000	0	0
Rap1/GTP	-0.02	0.072	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.039	0.055	-9999	-0.36	1	1
CCND1	0.041	0.025	-9999	-10000	0	0
VAV2	0.044	0.071	-9999	-0.43	1	1
RAP1/GDP	0.038	0.091	-9999	-0.3	1	1
adherens junction assembly	0.032	0.073	-9999	-0.47	1	1
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.016	0	-9999	-10000	0	0
PIP5K1C	0.016	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.046	0.053	-9999	-0.34	1	1
E-cadherin/beta catenin	-0.008	0.057	-9999	-0.43	1	1
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.032	0.076	-9999	-0.48	1	1
PIK3CA	0.002	0.095	-9999	-0.69	1	1
Rac1/GTP	-0.006	0.03	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	0.023	0.063	-9999	-0.44	1	1
ITGAE	0.016	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.023	0.079	-9999	-0.52	1	1

×

Sumoylation by RanBP2 regulates transcriptional repression

Figure S121. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S121. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	0.016	0	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	0.003	-9999	-9999
MDM2/SUMO1	0.034	0.009	-9999	-9999
HDAC4	0.013	0.022	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-9999
SUMO1	0.016	0	-9999	-9999
NPC/RanGAP1/SUMO1	0.019	0	-9999	-9999
mol:GTP	0	0	-9999	-9999
XPO1	0.032	0	-9999	-9999
EntrezGene:23636	0	0	-9999	-9999
RAN	0.016	0	-9999	-9999
EntrezGene:8021	0	0	-9999	-9999
RANBP2	0.016	0	-9999	-9999
SUMO1/HDAC4	0.034	0.009	-9999	-9999
SUMO1/HDAC1	0.035	0	-9999	-9999
RANGAP1	0.016	0	-9999	-9999
MDM2/SUMO1/SUMO1	0.039	0.011	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.025	0	-9999	-9999
Ran/GTP	0.031	0	-9999	-9999
EntrezGene:23225	0	0	-9999	-9999
MDM2	0.013	0.022	-9999	-9999
UBE2I	0.016	0	-9999	-9999
Ran/GTP/Exportin 1	0.038	0	-9999	-9999
NPC	0.009	0	-9999	-9999
PIAS2	0.016	0	-9999	-9999
PIAS1	0.016	0	-9999	-9999
EntrezGene:9972	0	0	-9999	-9999

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

Figure S122. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S122. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HIF3A	0.016	0	-9999	-9999
oxygen homeostasis	0	0	-9999	-9999
TCEB2	0.016	0	-9999	-9999
TCEB1	0.016	0	-9999	-9999
HIF1A/p53	0.037	0.01	-9999	-9999
HIF1A	0.029	0.01	-9999	-9999
COPS5	0.016	0	-9999	-9999
VHL/Elongin B/Elongin C/RBX1/CUL2	0.046	0	-9999	-9999
FIH (dimer)	0.016	0	-9999	-9999
CDKN2A	-0.051	0.08	-9999	-9999
ARNT/IPAS	0.023	0	-9999	-9999
HIF1AN	0.016	0	-9999	-9999
GNB2L1	0.016	0	-9999	-9999
HIF1A/ARNT	0.037	0.01	-9999	-9999
CUL2	0.016	0	-9999	-9999
OS9	0.016	0	-9999	-9999
RACK1/Elongin B/Elongin C	0.032	0	-9999	-9999
response to hypoxia	0	0	-9999	-9999
HIF1A/Hsp90	0.037	0.01	-9999	-9999
PHD1-3/OS9	0.021	0.034	-9999	-9999
HIF1A/RACK1/Elongin B/Elongin C	0.049	0.008	-9999	-9999
VHL	0.016	0	-9999	-9999
HSP90AA1	0.016	0	-9999	-9999
HIF1A/JAB1	0.037	0.01	-9999	-9999
EGLN3	-0.024	0.07	-9999	-9999
EGLN2	0.016	0	-9999	-9999
EGLN1	0.016	0	-9999	-9999
TP53	0.016	0	-9999	-9999
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.044	0.003	-9999	-9999
ARNT	0.016	0	-9999	-9999
ARD1A	0.016	0	-9999	-9999
RBX1	0.016	0	-9999	-9999
HIF1A/p19ARF	0.028	0.02	-9999	-9999

×

Rapid glucocorticoid signaling

Figure S123. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S123. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.028	0	-9999	-10000	0	0
MAPK9	0.002	0.055	-9999	-0.4	1	1
adrenocorticotropin secretion	0.007	0.024	-9999	-10000	0	0
GNB1/GNG2	0.021	0	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
MAPK14	0.01	0	-9999	-10000	0	0
Gs family/GTP	0.01	0	-9999	-10000	0	0
EntrezGene:2778	0	0	-9999	-10000	0	0
vasopressin secretion	0	0	-9999	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
glutamate secretion	0	0	-9999	-10000	0	0
GNAL	0.016	0	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
CRH	0.006	0.037	-9999	-10000	0	0
mol:cortisol	0	0	-9999	-10000	0	0
MAPK8	0.01	0	-9999	-10000	0	0
MAPK11	0.01	0	-9999	-10000	0	0

×

PDGFR-beta signaling pathway

Figure S124. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S124. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.17	0.21	-9999	-0.48	3	3
PDGFB-D/PDGFRB/SLAP	0.01	0.012	-9999	-10000	0	0
PDGFB-D/PDGFRB/APS/CBL	0.009	0.011	-9999	-10000	0	0
AKT1	0.04	0.097	-9999	-0.57	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.021	0.083	-9999	-0.42	1	1
PIK3CA	0.002	0.095	-9999	-0.69	1	1
FGR	-0.019	0.017	-9999	-10000	0	0
mol:Ca2+	-0.005	0.049	-9999	-10000	0	0
MYC	-0.005	0.075	-9999	-10000	0	0
SHC1	0.016	0	-9999	-10000	0	0
HRAS/GDP	0.038	0.006	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	0.014	0.016	-9999	-10000	0	0
GRB10	-0.024	0.16	-9999	-0.69	3	3
PTPN11	0.016	0	-9999	-10000	0	0
GO:0007205	-0.005	0.049	-9999	-10000	0	0
PTEN	0.002	0.095	-9999	-0.69	1	1
GRB2	0.016	0	-9999	-10000	0	0
GRB7	0.01	0.031	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHP2	0.01	0.012	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB10	-0.018	0.12	-9999	-0.52	3	3
cell cycle arrest	0.01	0.012	-9999	-10000	0	0
HRAS	0.016	0	-9999	-10000	0	0
HIF1A	0.047	0.086	-9999	-0.49	1	1
GAB1	-0.039	0.089	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
DNM2	-0.055	0.11	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.015	0.017	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.01	0.012	-9999	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.2	0.18	-9999	-0.5	3	3
positive regulation of MAPKKK cascade	0.01	0.012	-9999	-10000	0	0
PIK3R1	0.002	0.095	-9999	-0.69	1	1
mol:IP3	-0.005	0.049	-9999	-10000	0	0
E5	-0.002	0.002	-9999	-10000	0	0
CSK	0.016	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.007	0.021	-9999	-10000	0	0
SHB	0.016	0	-9999	-10000	0	0
BLK	-0.018	0.016	-9999	-10000	0	0
PTPN2	0.014	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.01	0.012	-9999	-10000	0	0
BCAR1	0.016	0	-9999	-10000	0	0
VAV2	-0.036	0.092	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.009	0.018	-9999	-10000	0	0
LCK	-0.02	0.018	-9999	-10000	0	0
PDGFRB	0.007	0.009	-9999	-10000	0	0
ACP1	0.016	0	-9999	-10000	0	0
HCK	-0.03	0.096	-9999	-0.72	1	1
ABL1	-0.016	0.062	-9999	-10000	0	0
PDGFB-D/PDGFRB/CBL	-0.026	0.075	-9999	-10000	0	0
PTPN1	0.014	0.002	-9999	-10000	0	0
SNX15	0.016	0	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
STAT1	0.006	0.037	-9999	-10000	0	0
cell proliferation	-0.004	0.072	-9999	-10000	0	0
SLA	0.016	0	-9999	-10000	0	0
actin cytoskeleton reorganization	0.019	0.057	-9999	-0.33	1	1
SRC	-0.018	0.016	-9999	-10000	0	0
PI3K	-0.018	0.096	-9999	-0.65	1	1
PDGFB-D/PDGFRB/GRB7/SHC	0.012	0.021	-9999	-10000	0	0
SH2B2	0	0	-9999	-10000	0	0
PLCgamma1/SPHK1	-0.022	0.085	-9999	-0.44	1	1
LYN	-0.018	0.017	-9999	-10000	0	0
LRP1	0.016	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
STAT5B	0.016	0	-9999	-10000	0	0
STAT5A	0.016	0	-9999	-10000	0	0
NCK1-2/p130 Cas	-0.007	0.048	-9999	-0.36	1	1
SPHK1	-0.001	0.096	-9999	-0.7	1	1
EDG1	-0.39	0.35	-9999	-0.69	31	31
mol:DAG	-0.005	0.049	-9999	-10000	0	0
PLCG1	-0.005	0.05	-9999	-10000	0	0
NHERF/PDGFRB	0.012	0.021	-9999	-10000	0	0
YES1	-0.02	0.018	-9999	-10000	0	0
cell migration	0.011	0.021	-9999	-10000	0	0
SHC/Grb2/SOS1	0.001	0.005	-9999	-10000	0	0
SLC9A3R2	0.01	0.031	-9999	-10000	0	0
SLC9A3R1	0.016	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.027	0.06	-9999	-0.39	1	1
FYN	-0.018	0.016	-9999	-10000	0	0
DOK1	0.033	0.005	-9999	-10000	0	0
HRAS/GTP	0.012	0	-9999	-10000	0	0
PDGFB	0.016	0	-9999	-10000	0	0
RAC1	-0.019	0.087	-9999	-10000	0	0
PRKCD	0.032	0.007	-9999	-10000	0	0
FER	0.032	0.007	-9999	-10000	0	0
MAPKKK cascade	0	0	-9999	-10000	0	0
RASA1	0.032	0.007	-9999	-10000	0	0
NCK1	0.002	0.095	-9999	-0.69	1	1
NCK2	0.016	0	-9999	-10000	0	0
p62DOK/Csk	0.044	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.01	0.012	-9999	-10000	0	0
chemotaxis	-0.015	0.061	-9999	-10000	0	0
STAT1-3-5/STAT1-3-5	0.001	0.006	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.006	0.007	-9999	-10000	0	0
PTPRJ	0.013	0.022	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase events

Figure S125. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S125. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
cAMP biosynthetic process	-0.015	-9999	-9999
PI3K Class IB/PDE3B	0.016	-9999	-9999
PDE3B	0.016	-9999	-9999

×

S1P4 pathway

Figure S126. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S126. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.016	0	-9999	-10000	0	0
CDC42/GTP	0.017	0.093	-9999	-0.57	1	1
PLCG1	0.018	0.097	-9999	-0.59	1	1
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.016	0	-9999	-10000	0	0
GNAI3	0.002	0.095	-9999	-0.69	1	1
G12/G13	0.023	0	-9999	-10000	0	0
cell migration	0.017	0.091	-9999	-0.56	1	1
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
MAPK3	0.018	0.097	-9999	-0.59	1	1
MAPK1	0.018	0.097	-9999	-0.59	1	1
S1P/S1P5/Gi	0.01	0.1	-9999	-0.37	3	3
GNAI1	-0.024	0.16	-9999	-0.69	3	3
CDC42/GDP	0.012	0	-9999	-10000	0	0
S1P/S1P5/G12	0.011	0	-9999	-10000	0	0
RHOA	0.027	0	-9999	-10000	0	0
S1P/S1P4/Gi	0.01	0.1	-9999	-0.37	3	3
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.016	0	-9999	-10000	0	0
S1P/S1P4/G12/G13	0.02	0	-9999	-10000	0	0
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

E-cadherin signaling events

Figure S127. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S127. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.023	0.063	-9999	-0.44	1	1
E-cadherin/beta catenin	0.013	0.072	-9999	-0.51	1	1
CTNNB1	0.016	0	-9999	-10000	0	0
JUP	0.016	0	-9999	-10000	0	0
CDH1	0.002	0.095	-9999	-0.69	1	1

×

p38 MAPK signaling pathway

Figure S128. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S128. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.007	0.075	-9999	-0.38	2	2
TRAF2/ASK1	0.002	0.088	-9999	-0.44	2	2
ATM	0.016	0	-9999	-10000	0	0
MAP2K3	0.036	0.068	-9999	-0.34	1	1
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.033	0.082	-9999	-0.34	2	2
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.016	0	-9999	-10000	0	0
TXN	0.01	0	-9999	-10000	0	0
CALM1	0.016	0	-9999	-10000	0	0
GADD45A	-0.014	0.13	-9999	-0.69	2	2
GADD45B	0.013	0.022	-9999	-10000	0	0
MAP3K1	0.002	0.095	-9999	-0.69	1	1
MAP3K6	0.016	0	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
MAP3K4	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	0.003	0.1	-9999	-0.51	2	2
TAK1/TAB family	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0.03	0	-9999	-10000	0	0
TRAF2	0.013	0.022	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.01	0.042	-9999	-10000	0	0
TRAF6	0.02	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	0.01	0.031	-9999	-10000	0	0
CCM2	0.016	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	0.018	0.016	-9999	-10000	0	0
MAPK11	0.016	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.011	0.082	-9999	-0.4	2	2
OSM/MEKK3	0.023	0	-9999	-10000	0	0
TAOK1	0.015	0.016	-9999	-10000	0	0
TAOK2	0.02	0	-9999	-10000	0	0
TAOK3	0.02	0	-9999	-10000	0	0
MAP3K7IP1	0.016	0	-9999	-10000	0	0
MAPK14	0.016	0	-9999	-10000	0	0
MAP3K7IP2	0.016	0	-9999	-10000	0	0
MAP3K5	-0.011	0.13	-9999	-0.69	2	2
MAP3K10	0.01	0.031	-9999	-10000	0	0
MAP3K3	0.016	0	-9999	-10000	0	0
TRX/ASK1	0.002	0.086	-9999	-0.44	2	2
GADD45/MTK1/MTK1	0.019	0.077	-9999	-0.37	2	2

×

Arf1 pathway

Figure S129. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S129. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
coatomer protein complex	0	0.003	-9999	-9999
EntrezGene:79658	0	0	-9999	-9999
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.02	0.003	-9999	-9999
AP2	0.023	0	-9999	-9999
mol:DAG	0	0	-9999	-9999
Arfaptin 2/Rac/GTP	0.022	0	-9999	-9999
CLTB	0.016	0	-9999	-9999
coatomer protein complex/ARF1/GTP/ER cargo protein	0.028	0	-9999	-9999
CD4	0.016	0	-9999	-9999
CLTA	0.016	0	-9999	-9999
mol:GTP	0.001	0.001	-9999	-9999
ARFGAP1	0.013	0	-9999	-9999
mol:PI-4-5-P2	-0.001	0.004	-9999	-9999
ARF1/GTP	-0.001	0.005	-9999	-9999
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.03	0	-9999	-9999
mol:Choline	-0.001	0.004	-9999	-9999
mol:GDP	0	0	-9999	-9999
ARF1	0.015	0	-9999	-9999
DDEF1	0	0.003	-9999	-9999
ARF1/GDP	0	0	-9999	-9999
AP2M1	0.016	0	-9999	-9999
EntrezGene:1313	0	0	-9999	-9999
actin filament polymerization	0.018	0	-9999	-9999
Rac/GTP	0.012	0	-9999	-9999
ARF1/GTP/GGA3/ARF-GAP1	0.028	0	-9999	-9999
ARFIP2	0.014	0.001	-9999	-9999
COPA	0.016	0	-9999	-9999
RAC1	0.016	0	-9999	-9999
ARF1/GTP/coatomer protein complex	0.026	0.002	-9999	-9999
ARF1/GTP/ARHGAP10	0	0.001	-9999	-9999
GGA3	0.016	0	-9999	-9999
ARF1/GTP/Membrin	0	0.001	-9999	-9999
AP2A1	0.016	0	-9999	-9999
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.03	0	-9999	-9999
ARF1/GDP/Membrin	0.018	0.002	-9999	-9999
Arfaptin 2/Rac/GDP	0.021	0.001	-9999	-9999
CYTH2	0.001	0.001	-9999	-9999
ARF1/GTP/GGA3	0.02	0	-9999	-9999
mol:ATP	0	0	-9999	-9999
Rac/GDP	0.012	0	-9999	-9999
mol:Brefeldin A	0	0	-9999	-9999
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.04	0	-9999	-9999
PLD2	-0.001	0.004	-9999	-9999
ARF-GAP1/v-SNARE	0.013	0	-9999	-9999
PIP5K1A	-0.001	0.004	-9999	-9999
ARF1/GTP/Membrin/GBF1/p115	0	0.002	-9999	-9999
mol:Phosphatic acid	0	0	-9999	-9999
mol:Phosphatidic acid	-0.001	0.004	-9999	-9999
KDEL Receptor/Ligand/ARF-GAP1	0.013	0	-9999	-9999
GOSR2	0	0.001	-9999	-9999
USO1	0	0.001	-9999	-9999
GBF1	0	0.001	-9999	-9999
ARF1/GTP/Arfaptin 2	0.021	0.001	-9999	-9999
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.032	0	-9999	-9999

×

Alternative NF-kappaB pathway

Figure S130. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S130. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.023	-9999	-9999
FBXW11	0.016	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.016	-9999	-9999
CHUK	0.016	-9999	-9999
NF kappa B2 p100/RelB	0.046	-9999	-9999
NFKB1	0.016	-9999	-9999
MAP3K14	0.016	-9999	-9999
NF kappa B1 p50/RelB	0.023	-9999	-9999
RELB	0.016	-9999	-9999
NFKB2	0.016	-9999	-9999
NF kappa B2 p52/RelB	0.021	-9999	-9999
regulation of B cell activation	0.021	-9999	-9999

×

Aurora B signaling

Figure S131. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S131. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.003	0.035	-9999	-10000	0	0
STMN1	-0.023	0.072	-9999	-10000	0	0
Aurora B/RasGAP/Survivin	-0.039	0.065	-9999	-10000	0	0
Chromosomal passenger complex/Cul3 protein complex	-0.08	0.13	-9999	-0.28	15	15
BIRC5	-0.086	0.081	-9999	-10000	0	0
DES	0.004	0.014	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.007	0.036	-9999	-10000	0	0
Aurora B/TACC1	0.003	0.036	-9999	-10000	0	0
Aurora B/PP2A	0.001	0.044	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.008	0.016	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0.001	0.002	-9999	-10000	0	0
NDC80	-0.065	0.079	-9999	-10000	0	0
Cul3 protein complex	-0.1	0.23	-9999	-0.46	15	15
KIF2C	-0.034	0.033	-9999	-10000	0	0
PEBP1	0.013	0.002	-9999	-10000	0	0
KIF20A	-0.11	0.066	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.001	0.044	-9999	-10000	0	0
SEPT1	0.016	0	-9999	-10000	0	0
SMC2	0.016	0	-9999	-10000	0	0
SMC4	0.01	0.031	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	0.012	0.024	-9999	-10000	0	0
PSMA3	0.016	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.001	-9999	-10000	0	0
H3F3B	0.007	0.024	-9999	-10000	0	0
AURKB	-0.02	0.07	-9999	-10000	0	0
AURKC	0.016	0	-9999	-10000	0	0
CDCA8	-0.068	0.083	-9999	-10000	0	0
cytokinesis	-0.037	0.066	-9999	-10000	0	0
Aurora B/Septin1	-0.03	0.063	-9999	-10000	0	0
AURKA	-0.018	0.066	-9999	-10000	0	0
INCENP	0.003	0.037	-9999	-10000	0	0
KLHL13	-0.18	0.32	-9999	-0.69	15	15
BUB1	-0.14	0.043	-9999	-10000	0	0
hSgo1/Aurora B/Survivin	-0.057	0.078	-9999	-10000	0	0
EVI5	0.015	0.001	-9999	-10000	0	0
RhoA/GTP	-0.048	0.062	-9999	-10000	0	0
SGOL1	-0.033	0.074	-9999	-10000	0	0
CENPA	-0.028	0.045	-9999	-10000	0	0
NCAPG	0	0	-9999	-10000	0	0
Aurora B/HC8 Proteasome	0.001	0.044	-9999	-10000	0	0
NCAPD2	0.013	0.022	-9999	-10000	0	0
Aurora B/PP1-gamma	0.001	0.044	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
NCAPH	-0.06	0.081	-9999	-10000	0	0
NPM1	0.006	0.022	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
KLHL9	0.002	0.095	-9999	-0.69	1	1
mitotic prometaphase	-0.003	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.001	0.043	-9999	-10000	0	0
PPP1CC	0.016	0	-9999	-10000	0	0
Centraspindlin	-0.053	0.075	-9999	-10000	0	0
RhoA/GDP	0.012	0	-9999	-10000	0	0
NSUN2	0.006	0.022	-9999	-10000	0	0
MYLK	-0.068	0.16	-9999	-0.4	10	10
KIF23	-0.046	0.08	-9999	-10000	0	0
VIM	-0.04	0.15	-9999	-0.54	4	4
RACGAP1	0.005	0.038	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	0.006	0.022	-9999	-10000	0	0
Chromosomal passenger complex	-0.046	0.051	-9999	-10000	0	0
Chromosomal passenger complex/EVI5	-0.048	0.085	-9999	-10000	0	0
TACC1	0.016	0	-9999	-10000	0	0
PPP2R5D	0.016	0	-9999	-10000	0	0
CUL3	0.016	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

pid_entity	TCGA.BK.A0CC	TCGA.BK.A0C9	TCGA.BG.A0MI	TCGA.BG.A0LW
109_MAP3K5	-0.3	0.061	0.061	0.061
47_PPARGC1A	0.016	0.016	0.016	0.016
105_BMP4	0.016	0.016	0.016	-0.15
105_BMP6	0.016	0.016	0.016	0.016
105_BMP7	-0.15	0.016	0.016	-0.15
105_BMP2	0.016	-0.69	0.016	-0.69
131_RELN/VLDLR	0.04	-0.039	-0.039	0.04
30_TGFB1/TGF beta receptor Type II	0.015	0.015	0.015	0.015
84_STAT5B	0.028	0.037	0.037	-0.059
84_STAT5A	0.028	0.037	0.037	-0.059