PARADIGM pathway analysis of mRNASeq expression data - Breast Invasive Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Class IB PI3K non-lipid kinase events	230
Signaling events mediated by Stem cell factor receptor (c-Kit)	219
EGFR-dependent Endothelin signaling events	185
Reelin signaling pathway	178
Signaling mediated by p38-alpha and p38-beta	164
HIF-1-alpha transcription factor network	154
p75(NTR)-mediated signaling	134
Glucocorticoid receptor regulatory network	127
FOXA2 and FOXA3 transcription factor networks	126
Lissencephaly gene (LIS1) in neuronal migration and development	112

Pathway.Name	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
Class IB PI3K non-lipid kinase events	230	690	3	-0.23	-1000	1000	-1000	-0.022	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	219	17102	78	-0.62	0.19	1000	-1000	-0.086	-1000
EGFR-dependent Endothelin signaling events	185	3885	21	-0.35	0	1000	-1000	-0.074	-1000
Reelin signaling pathway	178	9975	56	-0.52	0	1000	-1000	-0.1	-1000
Signaling mediated by p38-alpha and p38-beta	164	7258	44	-0.4	0	1000	-1000	-0.055	-1000
HIF-1-alpha transcription factor network	154	11771	76	-0.8	0.018	1000	-1000	-0.089	-1000
p75(NTR)-mediated signaling	134	16822	125	-0.44	0	1000	-1000	-0.1	-1000
Glucocorticoid receptor regulatory network	127	14578	114	-1	0.37	1000	-1000	-0.068	-1000
FOXA2 and FOXA3 transcription factor networks	126	5806	46	-1.2	0.026	1000	-1000	-0.041	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	112	6057	54	-0.52	0.022	1000	-1000	-0.09	-1000
Wnt signaling	106	746	7	-0.2	-0.006	1000	-1000	-0.052	-1000
Arf6 signaling events	104	6479	62	-0.35	0.017	1000	-1000	-0.068	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	104	7125	68	-0.53	0.16	1000	-1000	-0.11	-1000
IL4-mediated signaling events	102	9283	91	-1	0.52	1000	-1000	-0.14	-1000
Endothelins	101	9745	96	-0.4	0.038	1000	-1000	-0.07	-1000
Ephrin B reverse signaling	100	4844	48	-0.36	0.21	1000	-1000	-0.067	-1000
FOXM1 transcription factor network	98	5041	51	-0.46	0.012	1000	-1000	-0.14	-1000
EPHB forward signaling	97	8263	85	-0.36	0.2	1000	-1000	-0.097	-1000
Angiopoietin receptor Tie2-mediated signaling	95	8433	88	-0.35	0.031	1000	-1000	-0.099	-1000
ErbB2/ErbB3 signaling events	93	6074	65	-0.44	0.018	1000	-1000	-0.068	-1000
IGF1 pathway	84	4812	57	-0.19	0.081	1000	-1000	-0.097	-1000
BMP receptor signaling	82	6698	81	-0.58	0.024	1000	-1000	-0.095	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	80	6879	85	-0.27	0.012	1000	-1000	-0.068	-1000
ErbB4 signaling events	79	5498	69	-0.45	0.061	1000	-1000	-0.085	-1000
Calcium signaling in the CD4+ TCR pathway	78	2445	31	-0.38	0.011	1000	-1000	-0.086	-1000
Neurotrophic factor-mediated Trk receptor signaling	78	9456	120	-0.66	0.26	1000	-1000	-0.072	-1000
Nongenotropic Androgen signaling	76	3986	52	-0.25	0.11	1000	-1000	-0.06	-1000
Noncanonical Wnt signaling pathway	75	1956	26	-0.2	0	1000	-1000	-0.077	-1000
Signaling events regulated by Ret tyrosine kinase	74	6094	82	-0.17	0	1000	-1000	-0.087	-1000
Visual signal transduction: Rods	74	3857	52	-0.53	0	1000	-1000	-0.08	-1000
Glypican 1 network	73	3532	48	-0.34	0.025	1000	-1000	-0.048	-1000
IL23-mediated signaling events	71	4290	60	-0.49	0.018	1000	-1000	-0.14	-1000
Syndecan-1-mediated signaling events	70	2387	34	-0.22	0	1000	-1000	-0.07	-1000
Aurora C signaling	70	494	7	-0.16	0	1000	-1000	-0.039	-1000
IL6-mediated signaling events	66	5011	75	-0.31	0.054	1000	-1000	-0.073	-1000
Plasma membrane estrogen receptor signaling	66	5725	86	-0.2	0.081	1000	-1000	-0.076	-1000
Aurora B signaling	62	4197	67	-0.33	0.013	1000	-1000	-0.068	-1000
Signaling events mediated by PTP1B	60	4593	76	-0.68	0.068	1000	-1000	-0.08	-1000
amb2 Integrin signaling	60	4921	82	-0.54	0	1000	-1000	-0.08	-1000
Ephrin A reverse signaling	59	415	7	-0.083	0	1000	-1000	-0.04	-1000
Signaling events mediated by PRL	59	2034	34	-0.2	0.021	1000	-1000	-0.059	-1000
Integrins in angiogenesis	56	4744	84	-0.34	0	1000	-1000	-0.089	-1000
LPA receptor mediated events	52	5395	102	-0.29	0.029	1000	-1000	-0.078	-1000
RXR and RAR heterodimerization with other nuclear receptor	50	2627	52	-0.2	0.03	1000	-1000	-0.067	-1000
Signaling events mediated by the Hedgehog family	48	2514	52	-0.22	0.031	1000	-1000	-0.087	-1000
PDGFR-alpha signaling pathway	48	2127	44	-0.4	0.02	1000	-1000	-0.058	-1000
Visual signal transduction: Cones	46	1775	38	-0.18	0.007	1000	-1000	-0.07	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	43	1419	33	-0.6	0	1000	-1000	-0.057	-1000
Ras signaling in the CD4+ TCR pathway	43	733	17	-0.13	0	1000	-1000	-0.065	-1000
Syndecan-3-mediated signaling events	42	1489	35	-0.37	0	1000	-1000	-0.072	-1000
Presenilin action in Notch and Wnt signaling	41	2550	61	-0.44	0.013	1000	-1000	-0.069	-1000
Fc-epsilon receptor I signaling in mast cells	41	4063	97	-0.27	0.028	1000	-1000	-0.087	-1000
Signaling events mediated by HDAC Class III	41	1644	40	-0.61	0.03	1000	-1000	-0.043	-1000
TCGA08_rtk_signaling	41	1071	26	-0.29	0.027	1000	-1000	-0.033	-1000
Stabilization and expansion of the E-cadherin adherens junction	40	2967	74	-0.29	0.071	1000	-1000	-0.089	-1000
E-cadherin signaling in keratinocytes	40	1756	43	-0.29	0.044	1000	-1000	-0.073	-1000
Nephrin/Neph1 signaling in the kidney podocyte	38	1299	34	-0.075	0	1000	-1000	-0.072	-1000
Rapid glucocorticoid signaling	38	775	20	-0.19	0.027	1000	-1000	-0.032	-1000
LPA4-mediated signaling events	37	445	12	-0.17	0.019	1000	-1000	-0.016	-1000
FAS signaling pathway (CD95)	37	1781	47	-0.5	0.01	1000	-1000	-0.042	-1000
S1P1 pathway	35	1264	36	-0.33	0.007	1000	-1000	-0.068	-1000
Syndecan-4-mediated signaling events	33	2262	67	-0.34	0.004	1000	-1000	-0.082	-1000
Insulin-mediated glucose transport	31	994	32	-0.14	0.021	1000	-1000	-0.051	-1000
Nectin adhesion pathway	31	1994	63	-0.067	0.015	1000	-1000	-0.077	-1000
TCR signaling in naïve CD8+ T cells	31	2942	93	-0.18	0.085	1000	-1000	-0.068	-1000
Glypican 2 network	31	124	4	-0.033	-0.027	1000	-1000	-0.039	-1000
Canonical Wnt signaling pathway	30	1545	51	-0.44	0.15	1000	-1000	-0.058	-1000
IL27-mediated signaling events	29	1498	51	-0.32	0.014	1000	-1000	-0.065	-1000
IL12-mediated signaling events	28	2511	87	-0.39	0.055	1000	-1000	-0.1	-1000
Coregulation of Androgen receptor activity	27	2094	76	-0.18	0.034	1000	-1000	-0.049	-1000
PLK1 signaling events	27	2318	85	-0.22	0.036	1000	-1000	-0.055	-1000
Regulation of Androgen receptor activity	27	1921	70	-0.29	0.026	1000	-1000	-0.076	-1000
Regulation of p38-alpha and p38-beta	24	1310	54	-0.38	0.028	1000	-1000	-0.071	-1000
BCR signaling pathway	24	2379	99	-0.15	0.043	1000	-1000	-0.096	-1000
Insulin Pathway	24	1846	74	-0.19	0.032	1000	-1000	-0.084	-1000
Arf6 trafficking events	23	1657	71	-0.47	0.032	1000	-1000	-0.065	-1000
Thromboxane A2 receptor signaling	22	2341	105	-0.29	0.071	1000	-1000	-0.056	-1000
TCGA08_retinoblastoma	22	183	8	-0.046	0.008	1000	-1000	-0.021	-1000
IL2 signaling events mediated by STAT5	21	470	22	-0.12	0.067	1000	-1000	-0.054	-1000
Regulation of nuclear SMAD2/3 signaling	20	2780	136	-0.34	0.05	1000	-1000	-0.092	-1000
Effects of Botulinum toxin	20	524	26	-0.1	0	1000	-1000	-0.058	-1000
Regulation of Telomerase	20	2056	102	-0.35	0.022	1000	-1000	-0.08	-1000
TCGA08_p53	19	133	7	-0.02	0.014	1000	-1000	-0.022	-1000
Syndecan-2-mediated signaling events	18	1305	69	-0.2	0.038	1000	-1000	-0.067	-1000
Ceramide signaling pathway	17	1356	76	-0.18	0.047	1000	-1000	-0.064	-1000
E-cadherin signaling events	15	76	5	-0.024	0	1000	-1000	-0.044	-1000
Osteopontin-mediated events	14	532	38	-0.27	0.028	1000	-1000	-0.097	-1000
Hedgehog signaling events mediated by Gli proteins	14	953	65	-0.062	0.041	1000	-1000	-0.079	-1000
Class I PI3K signaling events mediated by Akt	14	1015	68	-0.28	0.053	1000	-1000	-0.057	-1000
TRAIL signaling pathway	14	701	48	-0.08	0.048	1000	-1000	-0.06	-1000
Caspase cascade in apoptosis	12	957	74	-0.054	0.046	1000	-1000	-0.056	-1000
Cellular roles of Anthrax toxin	12	471	39	-0.15	0.02	1000	-1000	-0.029	-1000
Signaling mediated by p38-gamma and p38-delta	12	188	15	-0.016	0.021	1000	-1000	-0.053	-1000
Retinoic acid receptors-mediated signaling	11	655	58	-0.1	0.039	1000	-1000	-0.069	-1000
JNK signaling in the CD4+ TCR pathway	10	171	17	-0.018	0.044	1000	-1000	-0.061	-1000
BARD1 signaling events	9	514	57	-0.11	0.022	1000	-1000	-0.064	-1000
Aurora A signaling	9	586	60	-0.2	0.005	1000	-1000	-0.061	-1000
S1P5 pathway	9	160	17	-0.043	0.024	1000	-1000	-0.052	-1000
E-cadherin signaling in the nascent adherens junction	9	708	76	-0.024	0.048	1000	-1000	-0.087	-1000
IL2 signaling events mediated by PI3K	8	502	58	-0.034	0.065	1000	-1000	-0.075	-1000
S1P3 pathway	8	362	42	-0.043	0.02	1000	-1000	-0.056	-1000
IL1-mediated signaling events	7	494	62	-0.039	0.032	1000	-1000	-0.097	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	7	582	83	-0.074	0.048	1000	-1000	-0.071	-1000
S1P4 pathway	7	181	25	-0.043	0	1000	-1000	-0.057	-1000
Signaling events mediated by HDAC Class II	6	484	75	-0.15	0.001	1000	-1000	-0.059	-1000
Sphingosine 1-phosphate (S1P) pathway	6	186	28	-0.043	0.019	1000	-1000	-0.051	-1000
p38 MAPK signaling pathway	6	269	44	-0.076	0.032	1000	-1000	-0.059	-1000
mTOR signaling pathway	5	301	53	-0.016	0.028	1000	-1000	-0.058	-1000
IFN-gamma pathway	5	340	68	-0.076	0.075	1000	-1000	-0.089	-1000
VEGFR1 specific signals	5	324	56	-0.17	0.063	1000	-1000	-0.085	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	4	106	23	-0.034	0.041	1000	-1000	-0.068	-1000
a4b1 and a4b7 Integrin signaling	4	23	5	-0.007	-0.002	1000	-1000	-0.032	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	4	220	45	-0.026	0.074	1000	-1000	-0.079	-1000
Signaling events mediated by VEGFR1 and VEGFR2	4	541	125	-0.17	0.086	1000	-1000	-0.1	-1000
Class I PI3K signaling events	4	294	73	-0.036	0.061	1000	-1000	-0.08	-1000
Circadian rhythm pathway	3	74	22	-0.018	0.046	1000	-1000	-0.052	-1000
HIF-2-alpha transcription factor network	3	155	43	-0.056	0.17	1000	-1000	-0.072	-1000
Signaling events mediated by HDAC Class I	3	323	104	-0.095	0.046	1000	-1000	-0.066	-1000
FoxO family signaling	3	236	64	-0.048	0.092	1000	-1000	-0.074	-1000
PDGFR-beta signaling pathway	3	317	97	-0.027	0.055	1000	-1000	-0.085	-1000
Arf6 downstream pathway	2	91	43	-0.013	0.022	1000	-1000	-0.039	-1000
EPO signaling pathway	2	123	55	-0.037	0.058	1000	-1000	-0.087	-1000
ceramide signaling pathway	2	131	49	-0.024	0.053	1000	-1000	-0.05	-1000
Atypical NF-kappaB pathway	2	73	31	-0.019	0.024	1000	-1000	-0.068	-1000
Canonical NF-kappaB pathway	1	76	39	-0.022	0.076	1000	-1000	-0.075	-1000
Paxillin-independent events mediated by a4b1 and a4b7	1	63	37	-0.048	0.035	1000	-1000	-0.073	-1000
Paxillin-dependent events mediated by a4b1	1	43	36	-0.008	0.022	1000	-1000	-0.073	-1000
PLK2 and PLK4 events	0	0	3	-0.014	0.012	1000	-1000	-0.027	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0	7	27	-0.001	0.028	1000	-1000	-0.051	-1000
Arf1 pathway	0	0	54	0	0.025	1000	-1000	-0.045	-1000
Alternative NF-kappaB pathway	0	5	13	-0.002	0	1000	-1000	-0.059	-1000
Total	5861	344851	7203	-32	-990	131000	-131000	-9	-131000

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	0.23	0.37	0.83	230	-10000	0	230
PI3K Class IB/PDE3B	-0.23	0.37	-10000	0	-0.84	230	230
PDE3B	-0.23	0.37	-10000	0	-0.84	230	230

×

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

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
MAP4K1	-0.15	0.22	-10000	0	-0.39	380	380
CRKL	-0.16	0.23	-10000	0	-0.41	379	379
HRAS	-0.16	0.17	-10000	0	-0.57	21	21
mol:PIP3	-0.17	0.21	-10000	0	-0.4	379	379
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0	0	-10000	0	-10000	0	0
GAB1	-0.2	0.22	-10000	0	-0.44	380	380
FOXO3	-0.14	0.21	-10000	0	-0.38	379	379
AKT1	-0.16	0.22	-10000	0	-0.41	379	379
BAD	-0.14	0.21	-10000	0	-0.37	379	379
megakaryocyte differentiation	-0.18	0.24	-10000	0	-0.43	380	380
GSK3B	-0.14	0.21	-10000	0	-0.37	379	379
RAF1	-0.089	0.17	-10000	0	-0.46	18	18
SHC1	0	0	-10000	0	-10000	0	0
STAT3	-0.18	0.24	-10000	0	-0.44	380	380
STAT1	-0.45	0.56	-10000	0	-1.1	386	386
HRAS/SPRED1	-0.13	0.14	-10000	0	-0.46	19	19
cell proliferation	-0.18	0.24	-10000	0	-0.43	380	380
PIK3CA	0	0.01	-10000	0	-10000	0	0
TEC	-0.002	0.041	-10000	0	-0.84	2	2
RPS6KB1	-0.18	0.24	-10000	0	-0.44	380	380
HRAS/SPRED2	-0.13	0.14	-10000	0	-0.46	19	19
LYN/TEC/p62DOK	-0.18	0.2	-10000	0	-0.4	380	380
MAPK3	-0.052	0.13	-10000	0	-0.32	16	16
STAP1	-0.2	0.24	-10000	0	-0.46	382	382
GRAP2	-0.014	0.1	-10000	0	-0.73	16	16
JAK2	-0.4	0.44	-10000	0	-0.87	386	386
STAT1 (dimer)	-0.44	0.55	-10000	0	-1	386	386
mol:Gleevec	0.006	0.009	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.18	0.2	-10000	0	-0.41	380	380
actin filament polymerization	-0.18	0.24	-10000	0	-0.44	380	380
LYN	0	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.27	0.34	-10000	0	-0.63	381	381
PIK3R1	0	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.17	0.18	-10000	0	-0.37	370	370
PI3K	-0.19	0.2	-10000	0	-0.41	379	379
PTEN	-0.002	0.041	-10000	0	-0.84	2	2
SCF/KIT/EPO/EPOR	-0.59	0.68	-10000	0	-1.3	379	379
MAPK8	-0.18	0.24	-10000	0	-0.44	380	380
STAT3 (dimer)	-0.18	0.24	-10000	0	-0.43	380	380
positive regulation of transcription	-0.04	0.11	-10000	0	-0.26	16	16
mol:GDP	-0.16	0.18	-10000	0	-0.51	38	38
PIK3C2B	-0.18	0.24	-10000	0	-0.44	380	380
CBL/CRKL	-0.18	0.19	-10000	0	-0.38	379	379
FER	-0.18	0.24	-10000	0	-0.44	383	383
SH2B3	-0.18	0.24	-10000	0	-0.44	380	380
PDPK1	-0.15	0.2	-10000	0	-0.36	379	379
SNAI2	-0.18	0.24	-10000	0	-0.45	381	381
positive regulation of cell proliferation	-0.32	0.41	-10000	0	-0.76	386	386
KITLG	0.001	0.068	-10000	0	-0.68	6	6
cell motility	-0.32	0.41	-10000	0	-0.76	386	386
PTPN6	0.014	0.021	-10000	0	-0.27	2	2
EPOR	-0.095	0.16	-10000	0	-10000	0	0
STAT5A (dimer)	-0.26	0.34	-10000	0	-0.62	387	387
SOCS1	-0.004	0.039	-10000	0	-0.34	9	9
cell migration	0.19	0.25	0.45	386	-10000	0	386
SOS1	0	0	-10000	0	-10000	0	0
EPO	-0.045	0.11	-10000	0	-0.3	85	85
VAV1	-0.002	0.032	-10000	0	-0.46	3	3
GRB10	-0.2	0.22	-10000	0	-0.44	380	380
PTPN11	0.012	0.013	-10000	0	-10000	0	0
SCF/KIT	-0.21	0.24	-10000	0	-0.47	380	380
GO:0007205	0.008	0.013	-10000	0	-10000	0	0
MAP2K1	-0.062	0.14	-10000	0	-0.36	16	16
CBL	0	0	-10000	0	-10000	0	0
KIT	-0.62	0.74	-10000	0	-1.4	378	378
MAP2K2	-0.062	0.14	-10000	0	-0.36	16	16
SHC/Grb2/SOS1	-0.18	0.2	-10000	0	-0.4	379	379
STAT5A	-0.27	0.35	-10000	0	-0.64	387	387
GRB2	0	0.01	-10000	0	-10000	0	0
response to radiation	-0.18	0.24	-10000	0	-0.44	381	381
SHC/GRAP2	-0.011	0.08	-10000	0	-0.64	13	13
PTPRO	-0.18	0.24	-10000	0	-0.44	380	380
SH2B2	-0.18	0.24	-10000	0	-0.44	380	380
DOK1	0	0	-10000	0	-10000	0	0
MATK	-0.19	0.25	-10000	0	-0.46	386	386
CREBBP	0.019	0.018	-10000	0	-10000	0	0
BCL2	-0.12	0.29	-10000	0	-1.6	24	24

×

EGFR-dependent Endothelin signaling events

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
HRAS	0	0.01	-9999	-10000	0	0
EGFR	-0.29	0.4	-9999	-0.83	297	297
EGF/EGFR	-0.29	0.33	-9999	-0.58	419	419
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.26	0.29	-9999	-0.53	410	410
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.17	0.33	-9999	-0.84	167	167
EGF/EGFR dimer/SHC	-0.3	0.33	-9999	-0.62	410	410
mol:GDP	-0.26	0.28	-9999	-0.52	410	410
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.066	0.22	-9999	-0.84	66	66
GRB2/SOS1	0	0.006	-9999	-10000	0	0
HRAS/GTP	-0.24	0.26	-9999	-0.48	410	410
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.24	0.26	-9999	-0.49	410	410
FRAP1	-0.25	0.27	-9999	-0.51	410	410
EGF/EGFR dimer	-0.35	0.37	-9999	-0.71	410	410
SOS1	0	0	-9999	-10000	0	0
GRB2	0	0.01	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.051	0.17	-9999	-0.64	66	66

×

Reelin signaling pathway

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
CDK5R1/CDK5	-0.006	0.032	-9999	-10000	0	0
VLDLR	-0.021	0.13	-9999	-0.84	21	21
CRKL	0	0	-9999	-10000	0	0
LRPAP1	0	0	-9999	-10000	0	0
FYN	-0.001	0.029	-9999	-0.84	1	1
ITGA3	-0.004	0.058	-9999	-0.84	4	4
RELN/VLDLR/Fyn	-0.36	0.29	-9999	-0.57	529	529
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.002	0.029	-9999	-0.48	3	3
AKT1	-0.21	0.17	-9999	-0.33	527	527
MAP2K7	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
DAB1	-0.017	0.066	-9999	-0.28	51	51
RELN/LRP8/DAB1	-0.35	0.26	-9999	-0.54	525	525
LRPAP1/LRP8	-0.021	0.057	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.32	0.24	-9999	-0.51	525	525
DAB1/alpha3/beta1 Integrin	-0.3	0.23	-9999	-0.6	120	120
long-term memory	-0.39	0.31	-9999	-0.57	571	571
DAB1/LIS1	-0.31	0.24	-9999	-0.49	529	529
DAB1/CRLK/C3G	-0.3	0.23	-9999	-0.6	119	119
PIK3CA	0	0.01	-9999	-10000	0	0
DAB1/NCK2	-0.31	0.24	-9999	-0.49	529	529
ARHGEF2	0	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.093	0.26	-9999	-0.84	90	90
CDK5R1	-0.009	0.048	-9999	-10000	0	0
RELN	-0.52	0.4	-9999	-0.84	524	524
PIK3R1	0	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.36	0.28	-9999	-0.58	524	524
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.37	0.3	-9999	-0.57	538	538
MAPK8	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.34	0.27	-9999	-0.54	529	529
ITGB1	0	0	-9999	-10000	0	0
MAP1B	-0.33	0.26	-9999	-0.52	532	532
RELN/LRP8	-0.36	0.28	-9999	-0.58	524	524
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.36	0.27	-9999	-0.54	558	558
PI3K	0	0.006	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.003	0.045	-9999	-0.64	4	4
RAP1A	-0.28	0.22	-9999	-0.55	118	118
PAFAH1B1	0	0	-9999	-10000	0	0
MAPK8IP1	-0.004	0.053	-9999	-0.52	7	7
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.071	0.23	-9999	-0.82	73	73
NCK2	0	0	-9999	-10000	0	0
neuron differentiation	-0.14	0.11	-9999	-0.56	3	3
neuron adhesion	-0.26	0.2	-9999	-0.62	36	36
LRP8	-0.034	0.091	-9999	-10000	0	0
GSK3B	-0.18	0.17	-9999	-0.44	48	48
RELN/VLDLR/DAB1/Fyn	-0.32	0.25	-9999	-0.51	529	529
MAP3K11	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.23	0.18	-9999	-0.36	529	529
CDK5	-0.001	0.019	-9999	-0.28	4	4
MAPT	-0.043	0.25	-9999	-0.78	84	84
neuron migration	-0.25	0.24	-9999	-0.5	135	135
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.14	0.11	-9999	-0.56	3	3
RELN/VLDLR	-0.34	0.27	-9999	-0.54	529	529

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.4	0.64	-9999	-1.3	281	281
MKNK1	0	0	-9999	-10000	0	0
MAPK14	-0.082	0.15	-9999	-0.39	11	11
ATF2/c-Jun	-0.056	0.17	-9999	-0.97	12	12
MAPK11	-0.084	0.16	-9999	-0.48	13	13
MITF	-0.092	0.2	-9999	-0.36	287	287
MAPKAPK5	-0.089	0.19	-9999	-0.35	284	284
KRT8	-0.095	0.19	-9999	-0.36	285	285
MAPKAPK3	0	0	-9999	-10000	0	0
MAPKAPK2	0	0.01	-9999	-0.28	1	1
p38alpha-beta/CK2	-0.12	0.23	-9999	-0.45	284	284
CEBPB	-0.089	0.19	-9999	-0.35	284	284
SLC9A1	-0.089	0.19	-9999	-0.35	284	284
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.082	0.19	-9999	-0.34	284	284
p38alpha-beta/MNK1	-0.12	0.17	-9999	-0.54	13	13
JUN	-0.054	0.16	-9999	-0.95	12	12
PPARGC1A	-0.22	0.37	-9999	-0.58	357	357
USF1	-0.089	0.19	-9999	-0.35	284	284
RAB5/GDP/GDI1	-0.085	0.12	-9999	-0.37	13	13
NOS2	-0.091	0.21	-9999	-1.1	7	7
DDIT3	-0.089	0.19	-9999	-0.35	284	284
RAB5A	0	0	-9999	-10000	0	0
HSPB1	-0.069	0.16	-9999	-0.42	27	27
p38alpha-beta/HBP1	-0.12	0.17	-9999	-0.54	13	13
CREB1	-0.092	0.2	-9999	-0.37	284	284
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.07	0.17	-9999	-0.49	11	11
RPS6KA4	-0.089	0.19	-9999	-0.35	284	284
PLA2G4A	-0.13	0.27	-9999	-0.74	99	99
GDI1	-0.089	0.19	-9999	-0.35	284	284
TP53	-0.12	0.24	-9999	-0.44	284	284
RPS6KA5	-0.092	0.19	-9999	-0.36	290	290
ESR1	-0.17	0.25	-9999	-0.42	383	383
HBP1	0	0	-9999	-10000	0	0
MEF2C	-0.09	0.19	-9999	-0.36	284	284
MEF2A	-0.089	0.19	-9999	-0.35	284	284
EIF4EBP1	-0.092	0.2	-9999	-0.37	284	284
KRT19	-0.1	0.21	-9999	-0.37	288	288
ELK4	-0.089	0.19	-9999	-0.35	284	284
ATF6	-0.089	0.19	-9999	-0.35	284	284
ATF1	-0.092	0.2	-9999	-0.37	284	284
p38alpha-beta/MAPKAPK2	-0.12	0.17	-9999	-0.53	14	14
p38alpha-beta/MAPKAPK3	-0.12	0.17	-9999	-0.54	13	13

×

HIF-1-alpha transcription factor network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.42	0.45	-9999	-1	221	221
HDAC7	0	0	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.34	0.31	-9999	-0.8	173	173
SMAD4	0	0	-9999	-10000	0	0
ID2	-0.42	0.45	-9999	-1	212	212
AP1	-0.22	0.31	-9999	-0.66	273	273
ABCG2	-0.45	0.48	-9999	-1.1	224	224
HIF1A	-0.054	0.06	-9999	-10000	0	0
TFF3	-0.5	0.52	-9999	-1.1	269	269
GATA2	-0.017	0.13	-9999	-0.79	21	21
AKT1	-0.057	0.079	-9999	-10000	0	0
response to hypoxia	-0.079	0.085	-9999	-0.25	25	25
MCL1	-0.42	0.45	-9999	-1	209	209
NDRG1	-0.43	0.45	-9999	-1	212	212
SERPINE1	-0.43	0.45	-9999	-1	210	210
FECH	-0.42	0.45	-9999	-1	212	212
FURIN	-0.42	0.45	-9999	-1	211	211
NCOA2	-0.004	0.077	-9999	-0.84	7	7
EP300	-0.058	0.12	-9999	-0.36	49	49
HMOX1	-0.43	0.45	-9999	-1	212	212
BHLHE40	-0.42	0.45	-9999	-1	224	224
BHLHE41	-0.43	0.47	-9999	-1	225	225
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.05	0.05	-9999	-10000	0	0
ENG	-0.04	0.046	-9999	-10000	0	0
JUN	-0.009	0.086	-9999	-0.84	9	9
RORA	-0.42	0.45	-9999	-1	215	215
ABCB1	-0.34	0.55	-9999	-1.5	160	160
TFRC	-0.43	0.45	-9999	-1	213	213
CXCR4	-0.43	0.45	-9999	-1	226	226
TF	-0.69	0.57	-9999	-1.1	456	456
CITED2	-0.42	0.45	-9999	-1	212	212
HIF1A/ARNT	-0.52	0.51	-9999	-1.2	227	227
LDHA	-0.051	0.047	-9999	-10000	0	0
ETS1	-0.43	0.45	-9999	-1	201	201
PGK1	-0.42	0.45	-9999	-1	215	215
NOS2	-0.43	0.46	-9999	-1	211	211
ITGB2	-0.43	0.45	-9999	-1	221	221
ALDOA	-0.43	0.45	-9999	-1	213	213
Cbp/p300/CITED2	-0.44	0.44	-9999	-1.1	196	196
FOS	-0.27	0.39	-9999	-0.84	272	272
HK2	-0.42	0.45	-9999	-1	221	221
SP1	0.012	0.024	-9999	-10000	0	0
GCK	-0.15	0.4	-9999	-1.6	53	53
HK1	-0.42	0.45	-9999	-1	200	200
NPM1	-0.42	0.45	-9999	-1	224	224
EGLN1	-0.42	0.45	-9999	-1	210	210
CREB1	0.018	0	-9999	-10000	0	0
PGM1	-0.42	0.45	-9999	-1	212	212
SMAD3	0	0	-9999	-10000	0	0
EDN1	-0.21	0.41	-9999	-1.2	100	100
IGFBP1	-0.53	0.53	-9999	-1.1	283	283
VEGFA	-0.26	0.31	-9999	-0.76	100	100
HIF1A/JAB1	-0.029	0.026	-9999	-10000	0	0
CP	-0.54	0.54	-9999	-1.2	295	295
CXCL12	-0.45	0.49	-9999	-1.1	236	236
COPS5	0.001	0.01	-9999	-0.28	1	1
SMAD3/SMAD4	0	0	-9999	-10000	0	0
BNIP3	-0.42	0.45	-9999	-1	215	215
EGLN3	-0.43	0.46	-9999	-1	217	217
CA9	-0.47	0.48	-9999	-1.1	229	229
TERT	-0.44	0.46	-9999	-1	229	229
ENO1	-0.42	0.45	-9999	-1	211	211
PFKL	-0.42	0.45	-9999	-1	224	224
NCOA1	-0.001	0.029	-9999	-0.84	1	1
ADM	-0.46	0.49	-9999	-1.1	232	232
ARNT	-0.059	0.052	-9999	-10000	0	0
HNF4A	-0.002	0.042	-9999	-0.28	14	14
ADFP	-0.43	0.45	-9999	-1	227	227
SLC2A1	-0.26	0.31	-9999	-0.76	102	102
LEP	-0.8	0.52	-9999	-1.1	484	484
HIF1A/ARNT/Cbp/p300	-0.36	0.32	-9999	-0.82	181	181
EPO	-0.23	0.24	-9999	-0.69	14	14
CREBBP	-0.058	0.12	-9999	-0.36	52	52
HIF1A/ARNT/Cbp/p300/HDAC7	-0.33	0.31	-9999	-0.83	144	144
PFKFB3	-0.43	0.46	-9999	-1	212	212
NT5E	-0.43	0.46	-9999	-1	212	212

×

p75(NTR)-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.001	0.022	-9999	-0.64	1	1
Necdin/E2F1	-0.081	0.15	-9999	-0.72	29	29
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.17	0.24	-9999	-0.49	286	286
NGF (dimer)/p75(NTR)/BEX1	-0.29	0.34	-9999	-0.66	347	347
NT-4/5 (dimer)/p75(NTR)	-0.44	0.44	-9999	-0.81	459	459
IKBKB	-0.001	0.014	-9999	-0.28	2	2
AKT1	-0.16	0.23	-9999	-0.48	284	284
IKBKG	0	0	-9999	-10000	0	0
BDNF	-0.073	0.23	-9999	-0.7	87	87
MGDIs/NGR/p75(NTR)/LINGO1	-0.22	0.27	-9999	-0.59	277	277
FURIN	-0.001	0.014	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.23	0.31	-9999	-0.61	312	312
LINGO1	-0.062	0.12	-9999	-0.28	187	187
Sortilin/TRAF6/NRIF	-0.001	0.029	-9999	-0.84	1	1
proBDNF (dimer)	-0.073	0.23	-9999	-0.7	87	87
NTRK1	-0.01	0.061	-9999	-0.84	2	2
RTN4R	-0.007	0.042	-9999	-0.28	20	20
neuron apoptosis	-0.16	0.28	-9999	-0.52	277	277
IRAK1	-0.001	0.014	-9999	-0.28	2	2
SHC1	-0.18	0.29	-9999	-0.57	284	284
ARHGDIA	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	-0.001	0.017	-9999	-0.48	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.18	0.25	-9999	-0.52	284	284
MAGEH1	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.2	0.28	-9999	-0.55	295	295
Mammalian IAPs/DIABLO	-0.006	0.048	-9999	-0.51	7	7
proNGF (dimer)	-0.017	0.11	-9999	-0.66	22	22
MAGED1	-0.001	0.014	-9999	-10000	0	0
APP	0	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.32	0.41	-9999	-0.84	324	324
ZNF274	0	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.17	0.24	-9999	-0.49	284	284
NGF	-0.017	0.11	-9999	-0.66	22	22
cell cycle arrest	-0.14	0.25	-9999	-0.48	284	284
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.12	0.17	-9999	-0.35	284	284
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.39	0.4	-9999	-0.72	459	459
NCSTN	0	0	-9999	-10000	0	0
mol:GTP	-0.2	0.28	-9999	-0.58	284	284
PSENEN	0	0.01	-9999	-10000	0	0
mol:ceramide	-0.18	0.25	-9999	-0.52	284	284
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.093	0.13	-9999	-0.5	13	13
p75(NTR)/beta APP	-0.21	0.3	-9999	-0.64	277	277
BEX1	-0.16	0.29	-9999	-0.53	255	255
mol:GDP	-0.18	0.29	-9999	-0.58	284	284
NGF (dimer)	-0.086	0.19	-9999	-0.53	129	129
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.2	0.24	-9999	-0.54	277	277
PIK3R1	0	0	-9999	-10000	0	0
RAC1/GTP	-0.17	0.24	-9999	-0.5	284	284
MYD88	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.2	0.28	-9999	-0.59	284	284
RHOB	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.06	0.083	-9999	-10000	0	0
NT3 (dimer)	-0.14	0.31	-9999	-0.84	135	135
TP53	-0.18	0.25	-9999	-0.49	312	312
PRDM4	-0.18	0.25	-9999	-0.52	284	284
BDNF (dimer)	-0.17	0.24	-9999	-0.61	174	174
PIK3CA	0	0.01	-9999	-10000	0	0
SORT1	-0.001	0.029	-9999	-0.84	1	1
activation of caspase activity	-0.17	0.23	-9999	-0.48	286	286
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.18	0.25	-9999	-0.52	284	284
RHOC	0	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
MAPK10	-0.18	0.28	-9999	-0.52	288	288
DIABLO	0	0	-9999	-10000	0	0
SMPD2	-0.18	0.25	-9999	-0.52	284	284
APH1B	-0.001	0.029	-9999	-0.84	1	1
APH1A	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.2	0.28	-9999	-0.57	284	284
PSEN1	0	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.31	0.38	-9999	-0.74	353	353
MAPK8	-0.13	0.25	-9999	-0.46	277	277
MAPK9	-0.13	0.25	-9999	-0.46	277	277
APAF1	0	0	-9999	-10000	0	0
NTF3	-0.14	0.31	-9999	-0.84	135	135
NTF4	-0.32	0.41	-9999	-0.84	324	324
NDN	-0.029	0.15	-9999	-0.84	29	29
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.16	0.22	-9999	-0.46	284	284
p75 CTF/Sortilin/TRAF6/NRIF	-0.001	0.018	-9999	-0.51	1	1
RhoA-B-C/GTP	-0.2	0.28	-9999	-0.58	284	284
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.2	0.27	-9999	-0.53	312	312
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.21	0.28	-9999	-0.56	312	312
PRKACB	-0.017	0.078	-9999	-0.32	46	46
proBDNF (dimer)/p75 ECD	-0.055	0.17	-9999	-0.64	66	66
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.01	0.082	-9999	-0.84	7	7
BIRC2	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.14	0.27	-9999	-0.5	284	284
BAD	-0.14	0.26	-9999	-0.47	279	279
RIPK2	-0.001	0.019	-9999	-0.28	4	4
NGFR	-0.28	0.39	-9999	-0.84	277	277
CYCS	-0.16	0.24	-9999	-0.49	284	284
ADAM17	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.18	0.25	-9999	-0.52	284	284
BCL2L11	-0.14	0.26	-9999	-0.47	279	279
BDNF (dimer)/p75(NTR)	-0.26	0.35	-9999	-0.7	312	312
PI3K	-0.18	0.25	-9999	-0.52	284	284
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.18	0.25	-9999	-0.52	284	284
NDNL2	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
PRKCI	0	0.01	-9999	-0.28	1	1
NGF (dimer)/p75(NTR)	-0.22	0.32	-9999	-0.66	284	284
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.18	0.25	-9999	-0.52	284	284
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
PRKCZ	-0.001	0.029	-9999	-0.84	1	1
PLG	-0.002	0.021	-9999	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.22	0.29	-9999	-0.56	319	319
SQSTM1	-0.001	0.014	-9999	-10000	0	0
NGFRAP1	-0.002	0.041	-9999	-0.84	2	2
CASP3	-0.12	0.24	-9999	-0.43	279	279
E2F1	-0.095	0.13	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
IKK complex	-0.074	0.12	-9999	-0.6	18	18
NGF (dimer)/TRKA	-0.019	0.096	-9999	-0.65	17	17
MMP7	-0.12	0.29	-9999	-0.84	116	116
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.17	0.24	-9999	-0.49	284	284
MMP3	-0.12	0.16	-9999	-0.84	12	12
APAF-1/Caspase 9	-0.12	0.18	-9999	-0.69	13	13

×

Glucocorticoid receptor regulatory network

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.025	0.079	0.34	3	-10000	0	3
SMARCC2	0.003	0.011	-10000	0	-10000	0	0
SMARCC1	0.003	0.01	-10000	0	-10000	0	0
TBX21	-0.15	0.26	-10000	0	-0.68	101	101
SUMO2	0	0.01	-10000	0	-0.28	1	1
STAT1 (dimer)	0.012	0.042	-10000	0	-0.34	1	1
FKBP4	-0.002	0.025	-10000	0	-10000	0	0
FKBP5	-0.012	0.096	-10000	0	-0.72	14	14
GR alpha/HSP90/FKBP51/HSP90	0.12	0.13	0.33	69	-0.44	13	82
PRL	-0.096	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.31	0.26	0.53	412	-0.56	5	417
RELA	-0.042	0.083	-10000	0	-10000	0	0
FGG	0.25	0.22	0.48	280	-0.51	1	281
GR beta/TIF2	0.14	0.14	0.34	102	-0.58	9	111
IFNG	-0.45	0.35	-10000	0	-0.75	425	425
apoptosis	-0.29	0.3	0.59	3	-0.67	234	237
CREB1	-0.008	0.028	-10000	0	-10000	0	0
histone acetylation	0.021	0.14	0.39	30	-0.36	30	60
BGLAP	-0.11	0.15	-10000	0	-0.45	43	43
GR/PKAc	0.12	0.12	0.32	57	-0.44	4	61
NF kappa B1 p50/RelA	-0.074	0.15	-10000	0	-0.42	25	25
SMARCD1	0.003	0.01	-10000	0	-10000	0	0
MDM2	0.13	0.1	0.26	198	-10000	0	198
GATA3	-0.029	0.16	-10000	0	-0.84	30	30
AKT1	0	0.005	-10000	0	-10000	0	0
CSF2	-0.043	0.11	-10000	0	-0.57	5	5
GSK3B	0	0.004	-10000	0	-10000	0	0
NR1I3	-0.22	0.27	0.56	3	-0.62	148	151
CSN2	0.21	0.17	0.41	213	-10000	0	213
BRG1/BAF155/BAF170/BAF60A	-0.002	0.032	-10000	0	-0.46	4	4
NFATC1	0.001	0.03	-10000	0	-0.84	1	1
POU2F1	0.007	0.013	-10000	0	-10000	0	0
CDKN1A	0.047	0.061	-10000	0	-1.5	1	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.008	0.008	-10000	0	-10000	0	0
SFN	-0.016	0.11	-10000	0	-0.62	21	21
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.11	0.14	0.33	50	-0.41	22	72
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.4	0.44	0.54	3	-0.9	325	328
JUN	-0.33	0.29	-10000	0	-0.61	356	356
IL4	-0.14	0.15	-10000	0	-0.46	49	49
CDK5R1	-0.009	0.049	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.46	0.42	-10000	0	-0.77	484	484
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.12	0.13	0.33	51	-0.41	10	61
cortisol/GR alpha (monomer)	0.37	0.31	0.62	443	-0.46	1	444
NCOA2	-0.007	0.076	-10000	0	-0.84	7	7
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.32	0.41	-10000	0	-0.9	272	272
AP-1/NFAT1-c-4	-0.7	0.53	-10000	0	-1	549	549
AFP	-0.63	0.71	-10000	0	-1.6	296	296
SUV420H1	0	0	-10000	0	-10000	0	0
IRF1	0.2	0.16	0.51	51	-10000	0	51
TP53	0.031	0.018	-10000	0	-0.5	1	1
PPP5C	0	0	-10000	0	-10000	0	0
KRT17	-0.89	0.82	-10000	0	-1.7	414	414
KRT14	-0.9	0.78	-10000	0	-1.6	475	475
TBP	0.019	0.001	-10000	0	-10000	0	0
CREBBP	0.15	0.14	0.28	361	-10000	0	361
HDAC1	0	0.003	-10000	0	-10000	0	0
HDAC2	0	0.003	-10000	0	-10000	0	0
AP-1	-0.71	0.54	-10000	0	-1	550	550
MAPK14	0	0.003	-10000	0	-10000	0	0
MAPK10	-0.14	0.31	-10000	0	-0.84	137	137
MAPK11	-0.002	0.042	-10000	0	-0.85	2	2
KRT5	-1	0.83	-10000	0	-1.7	476	476
interleukin-1 receptor activity	-0.001	0.003	-10000	0	-10000	0	0
NCOA1	0.005	0.03	-10000	0	-0.83	1	1
STAT1	0.012	0.042	-10000	0	-0.34	1	1
CGA	-0.17	0.18	-10000	0	-0.5	81	81
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.21	0.18	0.37	453	-10000	0	453
MAPK3	0	0.004	-10000	0	-10000	0	0
MAPK1	0	0.003	-10000	0	-10000	0	0
ICAM1	-0.19	0.25	-10000	0	-0.61	138	138
NFKB1	-0.042	0.083	-10000	0	-10000	0	0
MAPK8	-0.24	0.21	-10000	0	-0.45	344	344
MAPK9	0	0.003	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.31	0.32	0.59	3	-0.71	235	238
BAX	0.049	0.03	-10000	0	-10000	0	0
POMC	-0.2	0.31	-10000	0	-0.95	70	70
EP300	0.15	0.14	0.3	177	-10000	0	177
cortisol/GR alpha (dimer)/p53	0.33	0.25	0.55	413	-10000	0	413
proteasomal ubiquitin-dependent protein catabolic process	0.092	0.079	0.24	47	-10000	0	47
SGK1	0.24	0.2	0.41	112	-1.2	4	116
IL13	-0.34	0.28	-10000	0	-0.76	125	125
IL6	-0.53	0.64	-10000	0	-1.3	333	333
PRKACG	0	0	-10000	0	-10000	0	0
IL5	-0.29	0.22	-10000	0	-0.66	88	88
IL2	-0.44	0.35	-10000	0	-0.76	386	386
CDK5	-0.001	0.02	-10000	0	-0.29	4	4
PRKACB	-0.017	0.078	-10000	0	-0.32	46	46
HSP90AA1	0	0.01	-10000	0	-0.28	1	1
IL8	-0.22	0.31	-10000	0	-0.76	116	116
CDK5R1/CDK5	-0.006	0.035	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.062	0.098	-10000	0	-0.57	5	5
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.3	0.23	0.51	397	-10000	0	397
SMARCA4	0.003	0.014	-10000	0	-10000	0	0
chromatin remodeling	0.21	0.15	0.38	273	-10000	0	273
NF kappa B1 p50/RelA/Cbp	0.058	0.17	0.34	67	-0.42	1	68
JUN (dimer)	-0.33	0.29	-10000	0	-0.61	356	356
YWHAH	0	0	-10000	0	-10000	0	0
VIPR1	-0.14	0.26	-10000	0	-0.75	82	82
NR3C1	0.21	0.2	0.42	302	-0.63	2	304
NR4A1	-0.069	0.25	-10000	0	-0.79	90	90
TIF2/SUV420H1	-0.005	0.059	-10000	0	-0.64	7	7
MAPKKK cascade	-0.29	0.3	0.59	3	-0.67	234	237
cortisol/GR alpha (dimer)/Src-1	0.32	0.25	0.54	421	-10000	0	421
PBX1	0.005	0.044	-10000	0	-0.83	2	2
POU1F1	0.003	0.012	-10000	0	-10000	0	0
SELE	-0.23	0.36	-10000	0	-0.76	179	179
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.21	0.16	0.38	271	-10000	0	271
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.3	0.23	0.51	397	-10000	0	397
mol:cortisol	0.21	0.2	0.37	440	-10000	0	440
MMP1	-0.22	0.1	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.24	0.28	-9999	-0.8	91	91
PCK1	-1.1	0.72	-9999	-1.6	506	506
HNF4A	-0.25	0.28	-9999	-0.9	56	56
KCNJ11	-0.27	0.32	-9999	-0.91	85	85
AKT1	-0.14	0.14	-9999	-0.4	28	28
response to starvation	-0.001	0.006	-9999	-10000	0	0
DLK1	-0.5	0.57	-9999	-1.3	268	268
NKX2-1	-0.055	0.15	-9999	-10000	0	0
ACADM	-0.24	0.29	-9999	-0.86	72	72
TAT	-1.2	0.68	-9999	-1.6	616	616
CEBPB	0.002	0.005	-9999	-10000	0	0
CEBPA	-0.003	0.077	-9999	-0.84	7	7
TTR	-0.46	0.28	-9999	-0.74	303	303
PKLR	-0.24	0.28	-9999	-0.79	98	98
APOA1	-0.3	0.3	-9999	-0.96	58	58
CPT1C	-0.24	0.28	-9999	-0.82	82	82
ALAS1	-0.14	0.15	-9999	-10000	0	0
TFRC	-0.46	0.26	-9999	-0.74	271	271
FOXF1	-0.004	0.056	-9999	-0.47	9	9
NF1	0.016	0.029	-9999	-0.83	1	1
HNF1A (dimer)	0.003	0.027	-9999	-0.28	7	7
CPT1A	-0.24	0.28	-9999	-0.84	73	73
HMGCS1	-0.24	0.28	-9999	-0.83	79	79
NR3C1	-0.11	0.12	-9999	-0.39	46	46
CPT1B	-0.24	0.29	-9999	-0.83	84	84
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.002	0.006	-9999	-10000	0	0
GCK	-0.29	0.37	-9999	-1	117	117
CREB1	-0.057	0.066	-9999	-10000	0	0
IGFBP1	-0.46	0.61	-9999	-1.5	197	197
PDX1	-0.13	0.14	-9999	-10000	0	0
UCP2	-0.24	0.28	-9999	-0.82	81	81
ALDOB	-0.27	0.31	-9999	-0.89	82	82
AFP	-0.71	0.62	-9999	-1	539	539
BDH1	-0.24	0.28	-9999	-0.84	78	78
HADH	-0.26	0.3	-9999	-0.86	90	90
F2	-0.29	0.3	-9999	-0.95	61	61
HNF1A	0.003	0.027	-9999	-0.28	7	7
G6PC	-0.2	0.11	-9999	-0.64	7	7
SLC2A2	-0.16	0.17	-9999	-10000	0	0
INS	0.026	0.068	-9999	-10000	0	0
FOXA1	-0.25	0.28	-9999	-0.55	250	250
FOXA3	-0.43	0.22	-9999	-0.53	619	619
FOXA2	-0.32	0.34	-9999	-0.89	134	134
ABCC8	-0.34	0.44	-9999	-1.2	135	135
ALB	-0.98	0.65	-9999	-1.4	569	569

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0	0	-9999	-10000	0	0
VLDLR	-0.021	0.13	-9999	-0.84	21	21
LRPAP1	0	0	-9999	-10000	0	0
NUDC	0	0	-9999	-10000	0	0
RELN/LRP8	-0.36	0.28	-9999	-0.58	524	524
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0	0.01	-9999	-0.28	1	1
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.33	0.25	-9999	-0.52	524	524
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.017	0.066	-9999	-0.28	51	51
IQGAP1	0	0	-9999	-10000	0	0
PLA2G7	-0.015	0.089	-9999	-0.84	7	7
CALM1	0	0	-9999	-10000	0	0
DYNLT1	0	0.01	-9999	-0.28	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.021	0.057	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0	0	-9999	-10000	0	0
CDK5R1	-0.009	0.048	-9999	-10000	0	0
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.04	0.098	-9999	-0.28	122	122
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.37	0.29	-9999	-0.58	529	529
YWHAE	0	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.26	0.2	-9999	-0.47	151	151
MAP1B	-0.006	0.046	-9999	-0.39	12	12
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.29	0.22	-9999	-0.46	524	524
RELN	-0.52	0.4	-9999	-0.84	524	524
PAFAH/LIS1	-0.009	0.055	-9999	-0.56	7	7
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.2	0.16	-9999	-0.42	22	22
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.22	0.17	-9999	-0.41	98	98
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.28	0.22	-9999	-0.44	524	524
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.022	0	-9999	-10000	0	0
PAFAH1B3	-0.023	0.077	-9999	-0.28	71	71
PAFAH1B2	0	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	-0.004	0.029	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.24	0.19	-9999	-0.48	86	86
LRP8	-0.034	0.091	-9999	-10000	0	0
NDEL1/Katanin 60	-0.26	0.2	-9999	-0.47	152	152
P39/CDK5	-0.3	0.24	-9999	-0.48	524	524
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.29	0.25	-9999	-0.49	524	524
PPP2R5D	0	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.32	0.25	-9999	-0.5	529	529
RELN/VLDLR	-0.34	0.27	-9999	-0.54	529	529
CDC42	0	0	-9999	-10000	0	0

×

Wnt signaling

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
Noncanonical Wnts/FZD	-0.18	0.26	-9999	-0.46	322	322
FZD6	-0.006	0.07	-9999	-0.84	6	6
WNT6	-0.18	0.34	-9999	-0.84	177	177
WNT4	-0.024	0.13	-9999	-0.84	19	19
FZD3	-0.008	0.081	-9999	-0.84	8	8
WNT5A	-0.014	0.099	-9999	-0.84	11	11
WNT11	-0.2	0.35	-9999	-0.81	203	203

×

Arf6 signaling events

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
CENTA1/KIF3B	-0.004	0.051	-9999	-0.69	4	4
ARNO/beta Arrestin1-2	-0.14	0.21	-9999	-0.46	215	215
EGFR	-0.29	0.4	-9999	-0.83	297	297
EPHA2	-0.006	0.07	-9999	-0.84	6	6
USP6	0	0	-9999	-10000	0	0
IQSEC1	0	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.35	0.37	-9999	-0.71	410	410
ARRB2	-0.062	0.16	-9999	-0.46	115	115
mol:GTP	0.017	0.02	-9999	-0.16	5	5
ARRB1	-0.002	0.042	-9999	-0.65	3	3
FBXO8	0	0	-9999	-10000	0	0
TSHR	-0.039	0.18	-9999	-0.84	38	38
EGF	-0.17	0.33	-9999	-0.84	167	167
somatostatin receptor activity	0	0	-9999	-0.001	287	287
ARAP2	-0.006	0.071	-9999	-0.84	6	6
mol:GDP	-0.14	0.18	-9999	-0.37	253	253
mol:PI-3-4-5-P3	0	0	-9999	-0.001	229	229
ITGA2B	-0.017	0.078	-9999	-0.84	3	3
ARF6	0	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.004	0.044	-9999	-0.51	6	6
ADAP1	-0.004	0.053	-9999	-0.84	3	3
KIF13B	-0.002	0.041	-9999	-0.84	2	2
HGF/MET	-0.15	0.29	-9999	-0.69	178	178
PXN	0	0	-9999	-10000	0	0
ARF6/GTP	-0.13	0.16	-9999	-0.32	281	281
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.3	0.33	-9999	-0.62	410	410
ADRB2	-0.21	0.36	-9999	-0.84	214	214
receptor agonist activity	0	0	-9999	0	286	286
actin filament binding	0	0	-9999	-0.001	279	279
SRC	0	0.01	-9999	-10000	0	0
ITGB3	-0.015	0.11	-9999	-0.84	14	14
GNAQ	-0.002	0.041	-9999	-0.84	2	2
EFA6/PI-4-5-P2	0	0.001	-9999	-0.001	259	259
ARF6/GDP	-0.016	0.089	-9999	-0.44	16	16
ARF6/GDP/GULP/ACAP1	-0.15	0.21	-9999	-0.53	143	143
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.017	0.076	-9999	-0.52	17	17
ACAP1	-0.016	0.096	-9999	-0.44	31	31
ACAP2	0	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.095	0.24	-9999	-0.69	115	115
EFNA1	0	0.01	-9999	-10000	0	0
HGF	-0.05	0.2	-9999	-0.84	50	50
CYTH3	0.011	0	-9999	-10000	0	0
CYTH2	0.006	0.002	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	259	259
endosomal lumen acidification	0	0	-9999	-0.001	218	218
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.052	0.2	-9999	-0.84	52	52
GNAQ/ARNO	-0.001	0.024	-9999	-0.48	2	2
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	299	299
MET	-0.14	0.32	-9999	-0.83	144	144
GNA14	-0.013	0.082	-9999	-0.4	27	27
GNA15	-0.002	0.035	-9999	-0.39	5	5
GIT1	-0.001	0.019	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	283	283
GNA11	0	0	-9999	-10000	0	0
LHCGR	-0.12	0.29	-9999	-0.84	115	115
AGTR1	-0.21	0.35	-9999	-0.84	189	189
desensitization of G-protein coupled receptor protein signaling pathway	-0.094	0.24	-9999	-0.69	115	115
IPCEF1/ARNO	-0.24	0.26	-9999	-0.5	410	410
alphaIIb/beta3 Integrin	-0.023	0.099	-9999	-0.65	17	17

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.074	0.15	-10000	0	-0.37	105	105
NFATC2	-0.031	0.24	-10000	0	-0.78	65	65
NFATC3	-0.063	0.12	-10000	0	-0.31	32	32
CD40LG	-0.38	0.58	-10000	0	-1.2	258	258
ITCH	0.013	0.099	-10000	0	-10000	0	0
CBLB	0.013	0.099	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.23	0.34	-10000	0	-1	75	75
JUNB	0	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.036	0.1	-10000	0	-0.34	87	87
T cell anergy	-0.024	0.16	-10000	0	-0.48	87	87
TLE4	-0.01	0.24	-10000	0	-0.85	47	47
Jun/NFAT1-c-4/p21SNFT	-0.29	0.42	-10000	0	-0.93	213	213
AP-1/NFAT1-c-4	-0.53	0.66	-10000	0	-1.4	259	259
IKZF1	0.001	0.18	-10000	0	-0.63	52	52
T-helper 2 cell differentiation	-0.096	0.28	-10000	0	-0.79	81	81
AP-1/NFAT1	-0.24	0.34	-10000	0	-0.67	291	291
CALM1	-0.019	0.055	-10000	0	-10000	0	0
EGR2	-0.26	0.62	-10000	0	-1.6	120	120
EGR3	-0.38	0.73	-10000	0	-1.5	224	224
NFAT1/FOXP3	-0.09	0.2	-10000	0	-0.65	56	56
EGR1	-0.29	0.4	-10000	0	-0.84	287	287
JUN	-0.012	0.087	-10000	0	-0.84	9	9
EGR4	-0.016	0.064	-10000	0	-0.3	2	2
mol:Ca2+	-0.022	0.063	-10000	0	-10000	0	0
GBP3	-0.006	0.21	-10000	0	-0.72	53	53
FOSL1	-0.007	0.056	-10000	0	-0.84	2	2
NFAT1-c-4/MAF/IRF4	-0.31	0.46	-10000	0	-0.96	222	222
DGKA	0.002	0.18	-10000	0	-0.63	51	51
CREM	0	0.002	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.39	0.52	-10000	0	-1.1	253	253
CTLA4	-0.067	0.22	-10000	0	-0.66	50	50
NFAT1-c-4 (dimer)/EGR1	-0.44	0.57	-10000	0	-1.2	258	258
NFAT1-c-4 (dimer)/EGR4	-0.28	0.44	-10000	0	-0.91	232	232
FOS	-0.28	0.4	-10000	0	-0.85	272	272
IFNG	-0.14	0.25	-10000	0	-0.86	67	67
T cell activation	-0.17	0.35	-10000	0	-0.81	144	144
MAF	-0.001	0.029	-10000	0	-0.84	1	1
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.16	0.35	0.88	60	-10000	0	60
TNF	-0.32	0.52	-10000	0	-1.1	243	243
FASLG	-0.34	0.66	-10000	0	-1.2	267	267
TBX21	-0.026	0.17	-10000	0	-0.73	43	43
BATF3	-0.001	0.029	-10000	0	-0.84	1	1
PRKCQ	-0.027	0.16	-10000	0	-0.68	45	45
PTPN1	0	0.18	-10000	0	-0.63	52	52
NFAT1-c-4/ICER1	-0.29	0.43	-10000	0	-0.9	234	234
GATA3	-0.037	0.16	-10000	0	-0.84	30	30
T-helper 1 cell differentiation	-0.14	0.24	-10000	0	-0.83	70	70
IL2RA	-0.22	0.32	-10000	0	-0.9	90	90
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.002	0.18	-10000	0	-0.63	51	51
E2F1	-0.081	0.14	-10000	0	-10000	0	0
PPARG	-0.2	0.36	-10000	0	-0.84	197	197
SLC3A2	0.002	0.18	-10000	0	-0.63	52	52
IRF4	-0.074	0.23	-10000	0	-0.84	71	71
PTGS2	-0.48	0.66	-10000	0	-1.3	304	304
CSF2	-0.37	0.56	-10000	0	-1.1	251	251
JunB/Fra1/NFAT1-c-4	-0.27	0.41	-10000	0	-0.94	168	168
IL4	-0.1	0.3	-10000	0	-0.87	75	75
IL5	-0.37	0.56	-10000	0	-1.1	252	252
IL2	-0.17	0.36	-10000	0	-0.83	141	141
IL3	-0.064	0.066	-10000	0	-10000	0	0
RNF128	-0.063	0.28	-10000	0	-0.89	87	87
NFATC1	-0.16	0.35	-10000	0	-0.89	59	59
CDK4	0.077	0.22	0.61	23	-10000	0	23
PTPRK	-0.002	0.2	-10000	0	-0.71	47	47
IL8	-0.38	0.57	-10000	0	-1.1	257	257
POU2F1	0.001	0.011	-10000	0	-10000	0	0

×

IL4-mediated signaling events

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
BCL2L1	-0.46	0.45	-10000	0	-1.1	180	180
STAT6 (cleaved dimer)	-0.5	0.44	-10000	0	-1	290	290
IGHG1	-0.16	0.16	-10000	0	-0.35	131	131
IGHG3	-0.45	0.44	-10000	0	-0.94	286	286
AKT1	-0.21	0.24	-10000	0	-0.64	65	65
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.15	0.19	-10000	0	-0.62	36	36
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.22	0.24	-10000	0	-0.61	96	96
THY1	-0.46	0.45	-10000	0	-1.1	193	193
MYB	-0.015	0.11	-10000	0	-0.77	16	16
HMGA1	-0.009	0.05	-10000	0	-0.28	28	28
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.28	0.29	-10000	0	-0.66	183	183
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.22	0.23	-10000	0	-0.57	85	85
SP1	0.017	0.004	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.025	0.015	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.48	0.43	-10000	0	-1	247	247
SOCS1	-0.3	0.3	-10000	0	-0.73	161	161
SOCS3	-0.23	0.26	-10000	0	-0.81	51	51
FCER2	-0.62	0.66	-10000	0	-1.5	276	276
PARP14	0	0.019	-10000	0	-0.31	1	1
CCL17	-0.47	0.45	-10000	0	-1.1	175	175
GRB2	0	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.17	0.19	-10000	0	-0.57	23	23
T cell proliferation	-0.46	0.47	-10000	0	-1.1	203	203
IL4R/JAK1	-0.46	0.45	-10000	0	-1.1	185	185
EGR2	-0.59	0.61	-10000	0	-1.3	264	264
JAK2	-0.007	0.025	-10000	0	-10000	0	0
JAK3	0.008	0.035	-10000	0	-0.28	5	5
PIK3R1	0	0	-10000	0	-10000	0	0
JAK1	0.005	0.011	-10000	0	-10000	0	0
COL1A2	-0.14	0.15	-10000	0	-1.7	1	1
CCL26	-0.46	0.45	-10000	0	-1.1	176	176
IL4R	-0.49	0.48	-10000	0	-1.2	194	194
PTPN6	0.022	0.018	-10000	0	-0.26	2	2
IL13RA2	-0.46	0.45	-10000	0	-1.1	177	177
IL13RA1	-0.007	0.025	-10000	0	-10000	0	0
IRF4	-0.22	0.48	-10000	0	-1.6	86	86
ARG1	-0.11	0.12	-10000	0	-10000	0	0
CBL	-0.26	0.27	-10000	0	-0.64	154	154
GTF3A	0.013	0.016	-10000	0	-10000	0	0
PIK3CA	0	0.01	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.013	0.036	-10000	0	-10000	0	0
IRF4/BCL6	-0.2	0.42	-10000	0	-1.4	87	87
CD40LG	-0.035	0.19	-10000	0	-0.72	54	54
MAPK14	-0.26	0.27	-10000	0	-0.68	120	120
mitosis	-0.2	0.23	-10000	0	-0.61	65	65
STAT6	-0.52	0.52	-10000	0	-1.1	259	259
SPI1	0.007	0.021	-10000	0	-0.27	4	4
RPS6KB1	-0.19	0.22	-10000	0	-0.59	60	60
STAT6 (dimer)	-0.52	0.52	-10000	0	-1.1	265	265
STAT6 (dimer)/PARP14	-0.52	0.5	-10000	0	-1.1	286	286
mast cell activation	0.012	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.21	0.23	-10000	0	-0.66	48	48
FRAP1	-0.21	0.24	-10000	0	-0.64	65	65
LTA	-0.47	0.45	-10000	0	-1.1	174	174
FES	-0.003	0.05	-10000	0	-0.84	3	3
T-helper 1 cell differentiation	0.52	0.51	1.1	265	-10000	0	265
CCL11	-0.48	0.43	-10000	0	-1.1	213	213
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.21	0.23	-10000	0	-0.67	49	49
IL2RG	-0.004	0.085	-10000	0	-0.84	5	5
IL10	-0.46	0.46	-10000	0	-1.2	165	165
IRS1	-0.031	0.16	-10000	0	-0.84	31	31
IRS2	-0.038	0.17	-10000	0	-0.84	38	38
IL4	-0.11	0.11	-10000	0	-10000	0	0
IL5	-0.47	0.45	-10000	0	-1.1	187	187
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.38	0.35	-10000	0	-0.8	240	240
COL1A1	-0.18	0.16	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.46	0.46	-10000	0	-1.2	165	165
IL2R gamma/JAK3	-0.013	0.07	-10000	0	-0.44	17	17
TFF3	-0.56	0.58	-10000	0	-1.3	249	249
ALOX15	-0.55	0.57	-10000	0	-1.3	219	219
MYBL1	-0.046	0.1	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.4	0.37	-10000	0	-0.84	254	254
SHC1	0	0	-10000	0	-10000	0	0
CEBPB	0.008	0.009	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.22	0.23	-10000	0	-0.63	66	66
mol:PI-3-4-5-P3	-0.21	0.24	-10000	0	-0.64	65	65
PI3K	-0.22	0.25	-10000	0	-0.69	64	64
DOK2	-0.002	0.041	-10000	0	-0.84	2	2
ETS1	0.02	0.042	-10000	0	-0.8	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.16	0.18	-10000	0	-0.73	9	9
ITGB3	-0.47	0.47	-10000	0	-1.2	170	170
PIGR	-1	0.75	-10000	0	-1.6	548	548
IGHE	0.047	0.039	-10000	0	-10000	0	0
MAPKKK cascade	-0.15	0.18	-10000	0	-0.71	9	9
BCL6	0.003	0.042	-10000	0	-0.82	2	2
OPRM1	-0.47	0.45	-10000	0	-1.1	177	177
RETNLB	-0.47	0.45	-10000	0	-1.1	180	180
SELP	-0.65	0.68	-10000	0	-1.6	257	257
AICDA	-0.45	0.44	-10000	0	-1.1	175	175

×

Endothelins

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.019	0.19	-9999	-0.6	67	67
PTK2B	0	0	-9999	-10000	0	0
mol:Ca2+	0.029	0.16	-9999	-0.94	14	14
EDN1	-0.04	0.25	-9999	-0.86	66	66
EDN3	-0.4	0.42	-9999	-0.84	398	398
EDN2	-0.075	0.14	-9999	-0.29	214	214
HRAS/GDP	-0.027	0.19	-9999	-0.51	68	68
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0	0.13	-9999	-0.39	44	44
ADCY4	-0.15	0.29	-9999	-0.58	232	232
ADCY5	-0.28	0.36	-9999	-0.63	393	393
ADCY6	-0.13	0.27	-9999	-0.55	219	219
ADCY7	-0.13	0.27	-9999	-0.55	219	219
ADCY1	-0.15	0.29	-9999	-0.58	228	228
ADCY2	-0.17	0.33	-9999	-0.63	243	243
ADCY3	-0.13	0.27	-9999	-0.55	219	219
ADCY8	-0.14	0.27	-9999	-0.56	219	219
ADCY9	-0.13	0.27	-9999	-0.55	219	219
arachidonic acid secretion	-0.11	0.29	-9999	-0.46	289	289
ETB receptor/Endothelin-1/Gq/GTP	-0.029	0.17	-9999	-0.39	108	108
GNAO1	-0.033	0.14	-9999	-0.84	21	21
HRAS	0	0.01	-9999	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.038	0.2	-9999	-0.56	67	67
ETA receptor/Endothelin-1/Gs/GTP	-0.092	0.32	-9999	-0.59	219	219
mol:GTP	-0.001	0.006	-9999	-10000	0	0
COL3A1	-0.028	0.2	-9999	-0.6	67	67
EDNRB	-0.061	0.23	-9999	-0.84	69	69
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.027	0.22	-9999	-0.65	74	74
CYSLTR1	-0.025	0.21	-9999	-0.64	74	74
SLC9A1	0.002	0.099	-9999	-0.32	50	50
mol:GDP	-0.035	0.21	-9999	-0.54	75	75
SLC9A3	-0.04	0.25	-9999	-0.6	127	127
RAF1	-0.086	0.24	-9999	-0.52	125	125
JUN	0.029	0.17	-9999	-0.98	15	15
JAK2	-0.019	0.19	-9999	-0.6	67	67
mol:IP3	-0.024	0.16	-9999	-0.47	56	56
ETA receptor/Endothelin-1	0.036	0.24	-9999	-0.69	67	67
PLCB1	-0.049	0.2	-9999	-0.84	49	49
PLCB2	-0.001	0.03	-9999	-0.84	1	1
ETA receptor/Endothelin-3	-0.29	0.34	-9999	-0.65	398	398
FOS	-0.28	0.51	-9999	-0.99	278	278
Gai/GDP	-0.04	0.15	-9999	-0.79	21	21
CRK	0	0	-9999	-10000	0	0
mol:Ca ++	-0.045	0.23	-9999	-0.65	81	81
BCAR1	0	0.002	-9999	-10000	0	0
PRKCB1	-0.028	0.16	-9999	-0.44	60	60
GNAQ	0.007	0.042	-9999	-0.84	2	2
GNAZ	-0.006	0.07	-9999	-0.84	6	6
GNAL	-0.19	0.35	-9999	-0.84	190	190
Gs family/GDP	-0.17	0.26	-9999	-0.55	227	227
ETA receptor/Endothelin-1/Gq/GTP	0.017	0.12	-9999	-0.38	39	39
MAPK14	-0.025	0.16	-9999	-0.58	34	34
TRPC6	0.027	0.17	-9999	-1	14	14
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GNAI1	-0.043	0.18	-9999	-0.84	43	43
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.033	0.17	-9999	-0.41	97	97
ETB receptor/Endothelin-2	-0.1	0.2	-9999	-0.69	74	74
ETB receptor/Endothelin-3	-0.35	0.36	-9999	-0.68	435	435
ETB receptor/Endothelin-1	-0.077	0.27	-9999	-0.69	127	127
MAPK3	-0.21	0.42	-9999	-0.79	280	280
MAPK1	-0.21	0.42	-9999	-0.79	280	280
Rac1/GDP	-0.029	0.19	-9999	-0.52	63	63
cAMP biosynthetic process	-0.18	0.3	-9999	-0.62	227	227
MAPK8	0.027	0.14	-9999	-0.6	22	22
SRC	0	0.01	-9999	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.045	0.18	-9999	-0.6	48	48
p130Cas/CRK/Src/PYK2	-0.01	0.2	-9999	-0.58	47	47
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.029	0.19	-9999	-0.5	71	71
COL1A2	-0.048	0.24	-9999	-0.67	74	74
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.028	0.11	-9999	-0.64	6	6
mol:DAG	-0.025	0.16	-9999	-0.47	56	56
MAP2K2	-0.14	0.31	-9999	-0.56	280	280
MAP2K1	-0.14	0.31	-9999	-0.56	280	280
EDNRA	0.028	0.056	-9999	-0.33	1	1
positive regulation of muscle contraction	-0.01	0.17	-9999	-0.52	67	67
Gq family/GDP	-0.071	0.15	-9999	-0.59	38	38
HRAS/GTP	-0.05	0.2	-9999	-0.45	105	105
PRKCH	-0.019	0.16	-9999	-0.54	36	36
RAC1	0	0	-9999	-10000	0	0
PRKCA	-0.031	0.19	-9999	-0.59	53	53
PRKCB	-0.03	0.18	-9999	-0.55	51	51
PRKCE	-0.02	0.16	-9999	-0.53	38	38
PRKCD	-0.02	0.16	-9999	-0.53	37	37
PRKCG	-0.028	0.16	-9999	-0.52	43	43
regulation of vascular smooth muscle contraction	-0.32	0.58	-9999	-1.1	277	277
PRKCQ	-0.041	0.2	-9999	-0.58	69	69
PLA2G4A	-0.12	0.32	-9999	-0.5	289	289
GNA14	-0.004	0.084	-9999	-0.4	27	27
GNA15	0.006	0.036	-9999	-0.39	5	5
GNA12	0	0	-9999	-10000	0	0
GNA11	0.008	0.006	-9999	-10000	0	0
Rac1/GTP	0.038	0.2	-9999	-0.56	67	67
MMP1	-0.12	0.12	-9999	-10000	0	0

×

Ephrin B reverse 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
EFNB2	0	0	-10000	0	-10000	0	0
EPHB2	-0.004	0.037	-10000	0	-0.28	15	15
EFNB1	0.017	0.052	-10000	0	-0.65	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.19	0.22	-10000	0	-0.44	364	364
Ephrin B2/EPHB1-2	-0.22	0.25	-10000	0	-0.51	363	363
neuron projection morphogenesis	-0.18	0.21	-10000	0	-0.42	364	364
Ephrin B1/EPHB1-2/Tiam1	-0.21	0.24	-10000	0	-0.48	364	364
DNM1	-0.005	0.065	-10000	0	-0.75	6	6
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.003	0.13	-10000	0	-0.77	23	23
YES1	-0.023	0.16	-10000	0	-1	22	22
Ephrin B1/EPHB1-2/NCK2	-0.21	0.24	-10000	0	-0.48	364	364
PI3K	-0.021	0.13	-10000	0	-0.79	22	22
mol:GDP	-0.21	0.24	-10000	0	-0.47	364	364
ITGA2B	-0.017	0.078	-10000	0	-0.84	3	3
endothelial cell proliferation	0	0.005	-10000	0	-10000	0	0
FYN	-0.023	0.16	-10000	0	-1	22	22
MAP3K7	-0.021	0.13	-10000	0	-0.83	22	22
FGR	-0.025	0.16	-10000	0	-1	22	22
TIAM1	-0.001	0.019	-10000	0	-0.28	4	4
PIK3R1	0	0	-10000	0	-10000	0	0
RGS3	0	0	-10000	0	-10000	0	0
cell adhesion	-0.033	0.14	-10000	0	-0.63	38	38
LYN	-0.023	0.16	-10000	0	-1	22	22
Ephrin B1/EPHB1-2/Src Family Kinases	-0.025	0.15	-10000	0	-0.95	22	22
Ephrin B1/EPHB1-2	-0.028	0.14	-10000	0	-0.9	22	22
SRC	-0.025	0.16	-10000	0	-1	22	22
ITGB3	-0.015	0.11	-10000	0	-0.84	14	14
EPHB1	-0.36	0.41	-10000	0	-0.84	363	363
EPHB4	0	0.01	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0.005	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.023	0.099	-10000	0	-0.65	17	17
BLK	-0.025	0.16	-10000	0	-1	22	22
HCK	-0.025	0.16	-10000	0	-1	22	22
regulation of stress fiber formation	0.21	0.24	0.47	364	-10000	0	364
MAPK8	0.005	0.12	-10000	0	-0.72	23	23
Ephrin B1/EPHB1-2/RGS3	-0.21	0.24	-10000	0	-0.48	364	364
endothelial cell migration	-0.015	0.12	-10000	0	-0.73	22	22
NCK2	0	0	-10000	0	-10000	0	0
PTPN13	-0.015	0.15	-10000	0	-0.95	22	22
regulation of focal adhesion formation	0.21	0.24	0.47	364	-10000	0	364
chemotaxis	0.21	0.24	0.47	364	-10000	0	364
PIK3CA	0	0.01	-10000	0	-10000	0	0
Rac1/GTP	-0.19	0.22	-10000	0	-0.44	364	364
angiogenesis	-0.028	0.14	-10000	0	-0.89	22	22
LCK	-0.027	0.16	-10000	0	-1	22	22

×

FOXM1 transcription factor network

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
NFATC3	-0.23	0.41	-9999	-0.93	115	115
PLK1	-0.082	0.095	-9999	-10000	0	0
BIRC5	-0.091	0.091	-9999	-10000	0	0
HSPA1B	-0.23	0.41	-9999	-0.94	106	106
MAP2K1	0.007	0.028	-9999	-10000	0	0
BRCA2	-0.24	0.42	-9999	-0.95	112	112
FOXM1	-0.28	0.49	-9999	-1	172	172
XRCC1	-0.23	0.41	-9999	-0.96	100	100
FOXM1B/p19	-0.28	0.4	-9999	-0.92	161	161
Cyclin D1/CDK4	-0.22	0.39	-9999	-0.9	100	100
CDC2	-0.25	0.43	-9999	-0.89	172	172
TGFA	-0.22	0.41	-9999	-0.92	113	113
SKP2	-0.23	0.41	-9999	-0.98	90	90
CCNE1	-0.051	0.12	-9999	-0.29	163	163
CKS1B	-0.23	0.42	-9999	-0.96	101	101
RB1	-0.11	0.12	-9999	-1.3	1	1
FOXM1C/SP1	-0.31	0.4	-9999	-0.92	185	185
AURKB	-0.072	0.097	-9999	-10000	0	0
CENPF	-0.26	0.43	-9999	-0.92	149	149
CDK4	0.007	0.018	-9999	-0.3	1	1
MYC	-0.21	0.4	-9999	-0.86	126	126
CHEK2	0.006	0.031	-9999	-0.3	2	2
ONECUT1	-0.23	0.41	-9999	-0.9	126	126
CDKN2A	-0.032	0.1	-9999	-0.27	133	133
LAMA4	-0.23	0.42	-9999	-0.96	101	101
FOXM1B/HNF6	-0.26	0.46	-9999	-1	126	126
FOS	-0.46	0.68	-9999	-1.3	290	290
SP1	0	0	-9999	-10000	0	0
CDC25B	-0.23	0.42	-9999	-0.97	97	97
response to radiation	-0.008	0.028	-9999	-10000	0	0
CENPB	-0.23	0.41	-9999	-0.94	107	107
CENPA	-0.26	0.43	-9999	-0.97	122	122
NEK2	-0.28	0.42	-9999	-0.97	122	122
HIST1H2BA	-0.24	0.41	-9999	-0.96	100	100
CCNA2	-0.12	0.15	-9999	-0.29	369	369
EP300	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.27	0.46	-9999	-1.1	122	122
CCNB2	-0.26	0.43	-9999	-0.98	119	119
CCNB1	-0.25	0.44	-9999	-0.99	122	122
ETV5	-0.23	0.42	-9999	-0.92	119	119
ESR1	-0.33	0.56	-9999	-1.2	172	172
CCND1	-0.22	0.4	-9999	-0.91	107	107
GSK3A	0.012	0.02	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.083	0.13	-9999	-0.32	112	112
CDK2	0.005	0.008	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.011	0.034	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.32	0.36	-9999	-0.88	178	178
GAS1	-0.27	0.47	-9999	-1.1	118	118
MMP2	-0.24	0.42	-9999	-1	93	93
RB1/FOXM1C	-0.23	0.42	-9999	-0.94	117	117
CREBBP	0	0	-9999	-10000	0	0

×

EPHB forward signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.059	0.17	-10000	0	-0.57	83	83
cell-cell adhesion	0.2	0.23	0.72	59	-10000	0	59
Ephrin B/EPHB2/RasGAP	-0.042	0.13	-10000	0	-0.48	71	71
ITSN1	-0.002	0.041	-10000	0	-0.84	2	2
PIK3CA	0	0.01	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.002	0.015	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.24	0.28	-10000	0	-0.57	363	363
HRAS/GDP	-0.2	0.24	-10000	0	-0.69	75	75
Ephrin B/EPHB1/GRB7	-0.25	0.3	-10000	0	-0.55	380	380
Endophilin/SYNJ1	-0.039	0.12	-10000	0	-0.45	71	71
KRAS	0	0.01	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.25	0.29	-10000	0	-0.55	379	379
endothelial cell migration	0	0.005	-10000	0	-10000	0	0
GRB2	0	0.01	-10000	0	-10000	0	0
GRB7	-0.021	0.077	-10000	0	-0.29	62	62
PAK1	-0.045	0.15	-10000	0	-0.48	79	79
HRAS	0	0.01	-10000	0	-10000	0	0
RRAS	-0.04	0.13	-10000	0	-0.45	71	71
DNM1	-0.005	0.065	-10000	0	-0.74	6	6
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.23	0.28	-10000	0	-0.52	379	379
lamellipodium assembly	-0.2	0.23	-10000	0	-0.72	59	59
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.17	0.2	-10000	0	-0.38	363	363
PIK3R1	0	0	-10000	0	-10000	0	0
EPHB2	-0.005	0.037	-10000	0	-0.28	15	15
EPHB3	-0.003	0.029	-10000	0	-0.28	9	9
EPHB1	-0.36	0.42	-10000	0	-0.84	363	363
EPHB4	0	0.01	-10000	0	-10000	0	0
mol:GDP	-0.18	0.22	-10000	0	-0.69	72	72
Ephrin B/EPHB2	-0.043	0.14	-10000	0	-0.48	71	71
Ephrin B/EPHB3	-0.042	0.14	-10000	0	-0.48	71	71
JNK cascade	-0.2	0.23	-10000	0	-0.47	363	363
Ephrin B/EPHB1	-0.25	0.3	-10000	0	-0.55	379	379
RAP1/GDP	-0.15	0.19	-10000	0	-0.63	56	56
EFNB2	0	0	-10000	0	-10000	0	0
EFNB3	-0.071	0.23	-10000	0	-0.84	71	71
EFNB1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.22	0.26	-10000	0	-0.52	363	363
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.2	0.25	-10000	0	-0.8	59	59
Rap1/GTP	-0.2	0.23	-10000	0	-0.75	58	58
axon guidance	-0.058	0.17	-10000	0	-0.56	83	83
MAPK3	-0.12	0.2	-10000	0	-0.54	55	55
MAPK1	-0.12	0.2	-10000	0	-0.54	55	55
Rac1/GDP	-0.16	0.2	-10000	0	-0.61	71	71
actin cytoskeleton reorganization	-0.15	0.18	-10000	0	-0.56	56	56
CDC42/GDP	-0.16	0.2	-10000	0	-0.61	71	71
PI3K	0	0.005	-10000	0	-10000	0	0
EFNA5	-0.083	0.25	-10000	0	-0.84	83	83
Ephrin B2/EPHB4	0	0.005	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.03	0.1	-10000	0	-0.36	71	71
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.19	0.23	-10000	0	-0.71	59	59
PTK2	0.047	0.053	-10000	0	-10000	0	0
MAP4K4	-0.2	0.23	-10000	0	-0.47	363	363
SRC	0	0.01	-10000	0	-10000	0	0
KALRN	-0.014	0.11	-10000	0	-0.84	14	14
Intersectin/N-WASP	-0.002	0.031	-10000	0	-0.64	2	2
neuron projection morphogenesis	-0.15	0.18	-10000	0	-0.56	64	64
MAP2K1	-0.16	0.18	-10000	0	-0.57	56	56
WASL	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.22	0.25	-10000	0	-0.51	363	363
cell migration	-0.14	0.23	-10000	0	-0.57	78	78
NRAS	-0.001	0.014	-10000	0	-10000	0	0
SYNJ1	-0.04	0.13	-10000	0	-0.45	71	71
PXN	0	0	-10000	0	-10000	0	0
TF	-0.28	0.28	-10000	0	-0.48	506	506
HRAS/GTP	-0.21	0.25	-10000	0	-0.79	58	58
Ephrin B1/EPHB1-2	-0.22	0.26	-10000	0	-0.52	363	363
cell adhesion mediated by integrin	0.006	0.14	0.45	71	-10000	0	71
RAC1	0	0	-10000	0	-10000	0	0
mol:GTP	-0.23	0.27	-10000	0	-0.5	379	379
RAC1-CDC42/GTP	-0.2	0.23	-10000	0	-0.73	59	59
RASA1	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.15	0.19	-10000	0	-0.63	56	56
ruffle organization	-0.2	0.24	-10000	0	-0.74	59	59
NCK1	0	0	-10000	0	-10000	0	0
receptor internalization	0.001	0.14	-10000	0	-0.45	72	72
Ephrin B/EPHB2/KALRN	-0.05	0.16	-10000	0	-0.51	79	79
ROCK1	-0.001	0.012	-10000	0	-10000	0	0
RAS family/GDP	-0.13	0.16	-10000	0	-0.55	56	56
Rac1/GTP	-0.21	0.25	-10000	0	-0.79	59	59
Ephrin B/EPHB1/Src/Paxillin	-0.18	0.21	-10000	0	-0.39	379	379

×

Angiopoietin receptor Tie2-mediated signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.086	0.39	-10000	0	-0.91	149	149
NCK1/PAK1/Dok-R	-0.076	0.16	-10000	0	-0.42	149	149
NCK1/Dok-R	-0.2	0.44	-10000	0	-1.1	149	149
PIK3CA	0.002	0.011	-10000	0	-10000	0	0
mol:beta2-estradiol	0.03	0.094	0.25	131	-10000	0	131
RELA	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.031	0.1	0.38	2	-0.3	6	8
TNIP2	0	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.19	0.41	-10000	0	-1.1	149	149
FN1	-0.12	0.14	-10000	0	-10000	0	0
PLD2	-0.15	0.49	-10000	0	-1.2	149	149
PTPN11	0	0	-10000	0	-10000	0	0
GRB14	-0.1	0.23	-10000	0	-0.47	183	183
ELK1	-0.12	0.44	-10000	0	-1	149	149
GRB7	-0.021	0.077	-10000	0	-0.29	62	62
PAK1	-0.006	0.04	-10000	0	-0.28	18	18
Tie2/Ang1/alpha5/beta1 Integrin	-0.15	0.46	-10000	0	-1.1	149	149
CDKN1A	-0.04	0.26	-10000	0	-0.59	120	120
ITGA5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.2	0.44	-10000	0	-1.1	149	149
CRK	0	0	-10000	0	-10000	0	0
mol:NO	-0.041	0.29	-10000	0	-0.66	149	149
PLG	-0.16	0.49	-10000	0	-1.2	149	149
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.15	0.34	-10000	0	-0.88	149	149
GRB2	0	0.01	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
ANGPT2	-0.095	0.27	-10000	0	-0.78	74	74
BMX	-0.35	0.56	-10000	0	-1.4	152	152
ANGPT1	-0.2	0.54	-10000	0	-1.4	136	136
tube development	-0.055	0.29	-10000	0	-0.64	149	149
ANGPT4	-0.28	0.39	-10000	0	-0.84	277	277
response to hypoxia	-0.007	0.028	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.24	0.51	-10000	0	-1.3	149	149
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	-0.34	0.41	-10000	0	-0.84	337	337
STAT5A (dimer)	-0.069	0.33	-10000	0	-0.78	120	120
mol:L-citrulline	-0.041	0.29	-10000	0	-0.66	149	149
AGTR1	-0.2	0.35	-10000	0	-0.84	189	189
MAPK14	-0.14	0.47	-10000	0	-1.1	149	149
Tie2/SHP2	-0.075	0.24	-10000	0	-1.3	27	27
TEK	-0.086	0.28	-10000	0	-1.5	27	27
RPS6KB1	-0.082	0.37	-10000	0	-0.87	149	149
Angiotensin II/AT1	-0.16	0.27	-10000	0	-0.65	189	189
Tie2/Ang1/GRB2	-0.22	0.48	-10000	0	-1.2	149	149
MAPK3	-0.13	0.45	-10000	0	-1.1	149	149
MAPK1	-0.13	0.45	-10000	0	-1.1	149	149
Tie2/Ang1/GRB7	-0.21	0.49	-10000	0	-1.2	149	149
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.15	0.49	-10000	0	-1.2	149	149
PI3K	-0.12	0.44	-10000	0	-1.1	149	149
FES	-0.14	0.46	-10000	0	-1.1	149	149
Crk/Dok-R	-0.2	0.44	-10000	0	-1.1	149	149
Tie2/Ang1/ABIN2	-0.22	0.48	-10000	0	-1.2	149	149
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.069	0.34	-10000	0	-0.8	149	149
STAT5A	-0.007	0.076	-10000	0	-0.84	7	7
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.082	0.37	-10000	0	-0.87	149	149
Tie2/Ang2	-0.099	0.38	-10000	0	-0.92	124	124
Tie2/Ang1	-0.18	0.54	-10000	0	-1.3	149	149
FOXO1	-0.066	0.35	-10000	0	-0.81	150	150
ELF1	0.015	0.019	-10000	0	-10000	0	0
ELF2	-0.15	0.48	-10000	0	-1.2	149	149
mol:Choline	-0.14	0.46	-10000	0	-1.1	149	149
cell migration	-0.03	0.099	-10000	0	-0.25	30	30
FYN	-0.069	0.32	-10000	0	-0.76	124	124
DOK2	-0.002	0.041	-10000	0	-0.84	2	2
negative regulation of cell cycle	-0.032	0.24	-10000	0	-0.54	120	120
ETS1	-0.02	0.1	-10000	0	-1	2	2
PXN	-0.051	0.31	-10000	0	-0.71	149	149
ITGB1	0	0	-10000	0	-10000	0	0
NOS3	-0.056	0.33	-10000	0	-0.75	149	149
RAC1	0	0	-10000	0	-10000	0	0
TNF	-0.033	0.14	-10000	0	-0.84	12	12
MAPKKK cascade	-0.14	0.46	-10000	0	-1.1	149	149
RASA1	0	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.2	0.49	-10000	0	-1.2	149	149
NCK1	0	0	-10000	0	-10000	0	0
vasculogenesis	-0.03	0.26	-10000	0	-0.59	149	149
mol:Phosphatidic acid	-0.14	0.46	-10000	0	-1.1	149	149
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.041	0.29	-10000	0	-0.66	149	149
Rac1/GTP	-0.14	0.31	-10000	0	-0.81	149	149
MMP2	-0.15	0.5	-10000	0	-1.2	150	150

×

ErbB2/ErbB3 signaling events

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
USP8	0.013	0.01	-9999	-10000	0	0
RAS family/GTP	-0.11	0.14	-9999	-0.4	1	1
NFATC4	-0.09	0.16	-9999	-0.37	20	20
ERBB2IP	0.007	0.008	-9999	-10000	0	0
HSP90 (dimer)	0	0.01	-9999	-0.28	1	1
mammary gland morphogenesis	-0.15	0.2	-9999	-0.41	299	299
JUN	-0.019	0.079	-9999	-0.37	4	4
HRAS	0	0.01	-9999	-10000	0	0
DOCK7	-0.14	0.18	-9999	-0.39	299	299
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.18	0.24	-9999	-0.5	299	299
AKT1	0.007	0.006	-9999	-10000	0	0
BAD	0.018	0.004	-9999	-10000	0	0
MAPK10	-0.12	0.14	-9999	-0.37	137	137
mol:GTP	-0.001	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.16	0.21	-9999	-0.45	299	299
RAF1	-0.082	0.16	-9999	-0.42	1	1
ErbB2/ErbB3/neuregulin 2	-0.29	0.27	-9999	-0.54	448	448
STAT3	0	0.004	-9999	-10000	0	0
cell migration	-0.064	0.13	-9999	-0.32	67	67
mol:PI-3-4-5-P3	-0.002	0.003	-9999	-10000	0	0
cell proliferation	-0.14	0.23	-9999	-0.52	138	138
FOS	-0.17	0.27	-9999	-0.54	273	273
NRAS	-0.001	0.014	-9999	-10000	0	0
mol:Ca2+	-0.15	0.2	-9999	-0.41	299	299
MAPK3	-0.11	0.19	-9999	-0.49	53	53
MAPK1	-0.11	0.19	-9999	-0.49	53	53
JAK2	-0.14	0.18	-9999	-0.39	299	299
NF2	-0.007	0.01	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.13	0.18	-9999	-0.37	299	299
NRG1	-0.3	0.4	-9999	-0.84	298	298
GRB2/SOS1	0	0.006	-9999	-10000	0	0
MAPK8	-0.11	0.17	-9999	-0.34	299	299
MAPK9	-0.07	0.091	-9999	-10000	0	0
ERBB2	-0.017	0.055	-9999	-10000	0	0
ERBB3	-0.001	0.029	-9999	-0.84	1	1
SHC1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
apoptosis	0.017	0.017	-9999	-10000	0	0
STAT3 (dimer)	0	0.004	-9999	-10000	0	0
RNF41	0.018	0.014	-9999	-10000	0	0
FRAP1	0.007	0.005	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.1	0.13	-9999	-0.33	19	19
ErbB2/ErbB2/HSP90 (dimer)	-0.013	0.043	-9999	-10000	0	0
CHRNA1	-0.097	0.16	-9999	-0.41	53	53
myelination	-0.084	0.17	-9999	-0.36	20	20
PPP3CB	-0.13	0.17	-9999	-0.36	299	299
KRAS	0	0.01	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.11	0.15	-9999	-0.35	8	8
NRG2	-0.44	0.42	-9999	-0.84	447	447
mol:GDP	-0.13	0.18	-9999	-0.37	299	299
SOS1	0	0	-9999	-10000	0	0
MAP2K2	-0.075	0.15	-9999	-0.42	3	3
SRC	0	0.01	-9999	-10000	0	0
mol:cAMP	-0.002	0.003	-9999	-10000	0	0
PTPN11	-0.14	0.18	-9999	-0.39	299	299
MAP2K1	-0.14	0.21	-9999	-0.49	137	137
heart morphogenesis	-0.15	0.2	-9999	-0.41	299	299
RAS family/GDP	-0.11	0.14	-9999	-10000	0	0
GRB2	0	0.01	-9999	-10000	0	0
PRKACA	-0.011	0.014	-9999	-10000	0	0
CHRNE	0.007	0.022	-9999	-0.18	4	4
HSP90AA1	0	0.01	-9999	-0.28	1	1
activation of caspase activity	-0.007	0.006	-9999	-10000	0	0
nervous system development	-0.15	0.2	-9999	-0.41	299	299
CDC42	0	0	-9999	-10000	0	0

×

IGF1 pathway

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0	0	-10000	0	-10000	0	0
PTK2	0	0	-10000	0	-10000	0	0
CRKL	-0.12	0.24	-10000	0	-0.51	204	204
GRB2/SOS1/SHC	0	0.005	-10000	0	-10000	0	0
HRAS	0	0.01	-10000	0	-10000	0	0
IRS1/Crk	-0.13	0.24	-10000	0	-0.52	204	204
IGF-1R heterotetramer/IGF1/PTP1B	-0.13	0.24	-10000	0	-0.57	194	194
AKT1	-0.068	0.21	-10000	0	-0.75	29	29
BAD	-0.055	0.2	-10000	0	-0.68	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.12	0.24	-10000	0	-0.51	204	204
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.12	0.24	-10000	0	-0.52	204	204
RAF1	-0.048	0.19	-10000	0	-0.65	27	27
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.12	0.23	-10000	0	-0.49	204	204
YWHAZ	-0.001	0.017	-10000	0	-0.28	3	3
IGF-1R heterotetramer/IGF1/IRS1	-0.13	0.26	-10000	0	-0.56	204	204
PIK3CA	0	0.01	-10000	0	-10000	0	0
RPS6KB1	-0.068	0.21	-10000	0	-0.75	29	29
GNB2L1	0	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.041	0.16	-10000	0	-0.52	29	29
PXN	0	0	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
HRAS/GTP	-0.1	0.2	-10000	0	-0.78	29	29
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.1	0.2	-10000	0	-0.45	194	194
IGF-1R heterotetramer	-0.042	0.13	-10000	0	-0.86	18	18
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.12	0.24	-10000	0	-0.52	204	204
Crk/p130 Cas/Paxillin	-0.11	0.21	-10000	0	-0.83	29	29
IGF1R	-0.042	0.13	-10000	0	-0.86	18	18
IGF1	-0.19	0.36	-10000	0	-0.86	186	186
IRS2/Crk	-0.14	0.26	-10000	0	-0.55	209	209
PI3K	-0.12	0.22	-10000	0	-0.48	204	204
apoptosis	0.081	0.15	0.56	30	-10000	0	30
HRAS/GDP	0	0.006	-10000	0	-10000	0	0
PRKCD	-0.098	0.26	-10000	0	-0.55	194	194
RAF1/14-3-3 E	-0.076	0.14	-10000	0	-0.54	27	27
BAD/14-3-3	-0.086	0.16	-10000	0	-0.61	30	30
PRKCZ	-0.069	0.21	-10000	0	-0.74	30	30
Crk/p130 Cas/Paxillin/FAK1	-0.085	0.16	-10000	0	-0.64	27	27
PTPN1	-0.004	0.032	-10000	0	-0.28	11	11
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.14	0.26	-10000	0	-0.59	194	194
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.11	0.22	-10000	0	-0.49	194	194
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.12	0.23	-10000	0	-0.51	204	204
GRB10	0	0	-10000	0	-10000	0	0
PTPN11	-0.12	0.24	-10000	0	-0.51	204	204
IRS1	-0.14	0.25	-10000	0	-0.56	204	204
IRS2	-0.15	0.28	-10000	0	-0.57	216	216
IGF-1R heterotetramer/IGF1	-0.16	0.3	-10000	0	-0.7	194	194
GRB2	0	0.01	-10000	0	-10000	0	0
PDPK1	-0.11	0.21	-10000	0	-0.46	194	194
YWHAE	0	0	-10000	0	-10000	0	0
PRKD1	-0.11	0.28	-10000	0	-0.59	204	204
SHC1	0	0	-10000	0	-10000	0	0

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	-0.11	0.2	-9999	-0.63	95	95
SMAD6-7/SMURF1	-0.001	0.019	-9999	-0.56	1	1
NOG	-0.025	0.13	-9999	-0.84	20	20
SMAD9	-0.096	0.25	-9999	-0.85	70	70
SMAD4	0	0	-9999	-10000	0	0
SMAD5	-0.079	0.18	-9999	-0.49	109	109
BMP7/USAG1	-0.36	0.36	-9999	-0.7	434	434
SMAD5/SKI	-0.089	0.16	-9999	-0.52	76	76
SMAD1	0.024	0.031	-9999	-10000	0	0
BMP2	-0.15	0.32	-9999	-0.83	153	153
SMAD1/SMAD1/SMAD4	-0.002	0.013	-9999	-10000	0	0
BMPR1A	-0.001	0.029	-9999	-0.84	1	1
BMPR1B	-0.14	0.17	-9999	-0.3	377	377
BMPR1A-1B/BAMBI	-0.092	0.15	-9999	-0.64	45	45
AHSG	-0.002	0.025	-9999	-10000	0	0
CER1	-0.001	0.014	-9999	-10000	0	0
BMP2-4/CER1	-0.14	0.26	-9999	-0.61	188	188
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.11	0.2	-9999	-0.52	116	116
BMP2-4 (homodimer)	-0.15	0.29	-9999	-0.69	188	188
RGMB	-0.001	0.029	-9999	-0.84	1	1
BMP6/BMPR2/BMPR1A-1B	-0.1	0.17	-9999	-0.57	89	89
RGMA	-0.11	0.28	-9999	-0.84	112	112
SMURF1	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.11	0.2	-9999	-0.55	107	107
BMP2-4/USAG1	-0.4	0.39	-9999	-0.69	483	483
SMAD6/SMURF1/SMAD5	-0.089	0.16	-9999	-0.52	76	76
SOSTDC1	-0.41	0.42	-9999	-0.84	410	410
BMP7/BMPR2/BMPR1A-1B	-0.1	0.17	-9999	-0.6	77	77
SKI	0	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.072	0.23	-9999	-0.83	73	73
HFE2	-0.002	0.025	-9999	-0.28	7	7
ZFYVE16	0	0	-9999	-10000	0	0
MAP3K7	0	0.01	-9999	-0.28	1	1
BMP2-4/CHRD	-0.15	0.28	-9999	-0.64	190	190
SMAD5/SMAD5/SMAD4	-0.089	0.16	-9999	-0.52	76	76
MAPK1	0	0	-9999	-10000	0	0
TAK1/TAB family	-0.088	0.17	-9999	-0.54	80	80
BMP7 (homodimer)	-0.074	0.22	-9999	-0.63	99	99
NUP214	0	0	-9999	-10000	0	0
BMP6/FETUA	-0.057	0.18	-9999	-0.65	72	72
SMAD1/SKI	-0.005	0.014	-9999	-10000	0	0
SMAD6	-0.001	0.029	-9999	-0.84	1	1
CTDSP2	0	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.14	0.26	-9999	-0.61	188	188
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.041	0.12	-9999	-0.33	105	105
BMPR2 (homodimer)	0	0	-9999	-10000	0	0
GADD34/PP1CA	-0.001	0.01	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.089	0.12	-9999	-0.65	19	19
CHRDL1	-0.58	0.39	-9999	-0.84	582	582
ENDOFIN/SMAD1	-0.005	0.014	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.004	0.016	-9999	-10000	0	0
SMAD6/SMURF1	0	0	-9999	-10000	0	0
BAMBI	-0.036	0.15	-9999	-0.84	26	26
SMURF2	0	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.51	0.39	-9999	-0.72	597	597
BMP2-4/GREM1	-0.16	0.27	-9999	-0.62	191	191
SMAD7	0	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.091	0.23	-9999	-0.8	70	70
SMAD1/SMAD6	-0.005	0.014	-9999	-10000	0	0
TAK1/SMAD6	0	0.006	-9999	-10000	0	0
BMP7	-0.074	0.22	-9999	-0.63	99	99
BMP6	-0.072	0.23	-9999	-0.83	73	73
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.1	0.19	-9999	-0.61	79	79
PPM1A	0	0	-9999	-10000	0	0
SMAD1/SMURF2	-0.005	0.014	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0	0	-9999	-10000	0	0
PPP1CA	-0.002	0.021	-9999	-0.28	5	5
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
PPP1R15A	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.13	0.24	-9999	-0.47	202	202
CHRD	-0.03	0.13	-9999	-0.43	59	59
BMPR2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.13	0.24	-9999	-0.47	213	213
BMP4	-0.051	0.2	-9999	-0.83	52	52
FST	-0.033	0.16	-9999	-0.79	35	35
BMP2-4/NOG	-0.15	0.28	-9999	-0.62	199	199
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.092	0.16	-9999	-0.56	77	77

×

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

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.11	0.24	-10000	0	-0.64	143	143
CRKL	-0.041	0.16	-10000	0	-0.36	143	143
mol:PIP3	-0.017	0.041	0.82	2	-10000	0	2
AKT1	0.004	0.025	0.5	2	-10000	0	2
PTK2B	0	0	-10000	0	-10000	0	0
RAPGEF1	-0.031	0.15	-10000	0	-0.56	15	15
RANBP10	0	0	-10000	0	-10000	0	0
PIK3CA	0	0.01	-10000	0	-10000	0	0
HGF/MET/SHIP2	-0.13	0.25	-10000	0	-0.6	178	178
MAP3K5	-0.021	0.15	-10000	0	-0.55	17	17
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.12	0.23	-10000	0	-0.55	178	178
AP1	-0.22	0.29	-10000	0	-0.62	273	273
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	-0.25	0.37	-10000	0	-0.78	273	273
STAT3 (dimer)	-0.073	0.15	-10000	0	-0.34	178	178
GAB1/CRKL/SHP2/PI3K	-0.061	0.12	-10000	0	-0.53	15	15
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	-0.067	0.13	-10000	0	-0.56	15	15
PTPN11	0	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
PTEN	-0.002	0.041	-10000	0	-0.84	2	2
ELK1	-0.045	0.11	-10000	0	-0.28	143	143
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.047	0.095	-10000	0	-0.23	143	143
PAK1	0.009	0.03	0.46	2	-10000	0	2
HGF/MET/RANBP10	-0.13	0.25	-10000	0	-0.6	178	178
HRAS	-0.15	0.3	-10000	0	-0.72	178	178
DOCK1	-0.031	0.15	-10000	0	-0.33	143	143
GAB1	-0.051	0.17	-10000	0	-0.36	178	178
CRK	-0.041	0.16	-10000	0	-0.36	143	143
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.16	0.31	-10000	0	-0.73	178	178
JUN	-0.009	0.086	-10000	0	-0.84	9	9
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.079	0.16	-10000	0	-0.37	178	178
PIK3R1	0	0	-10000	0	-10000	0	0
cell morphogenesis	-0.015	0.17	-10000	0	-0.6	15	15
GRB2/SHC	-0.068	0.14	-10000	0	-0.34	143	143
FOS	-0.27	0.39	-10000	0	-0.84	272	272
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.045	0.11	-10000	0	-0.28	143	143
HGF/MET/MUC20	-0.13	0.26	-10000	0	-0.61	178	178
cell migration	-0.067	0.13	-10000	0	-0.34	143	143
GRB2	0	0.01	-10000	0	-10000	0	0
CBL	0	0	-10000	0	-10000	0	0
MET/RANBP10	-0.11	0.24	-10000	0	-0.64	143	143
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.078	0.16	-10000	0	-0.37	178	178
MET/MUC20	-0.11	0.25	-10000	0	-0.65	144	144
RAP1B	-0.021	0.14	-10000	0	-0.52	15	15
RAP1A	-0.021	0.14	-10000	0	-0.52	15	15
HGF/MET/RANBP9	-0.13	0.25	-10000	0	-0.6	178	178
RAF1	-0.1	0.3	-10000	0	-0.73	143	143
STAT3	-0.074	0.15	-10000	0	-0.35	178	178
cell proliferation	-0.062	0.23	-10000	0	-0.5	178	178
RPS6KB1	-0.027	0.054	-10000	0	-0.19	15	15
MAPK3	-0.045	0.095	-10000	0	-0.26	143	143
MAPK1	-0.045	0.095	-10000	0	-0.26	143	143
RANBP9	0	0	-10000	0	-10000	0	0
MAPK8	0.001	0.13	-10000	0	-0.43	16	16
SRC	-0.072	0.14	-10000	0	-0.64	15	15
PI3K	-0.068	0.14	-10000	0	-0.34	143	143
MET/Glomulin	-0.1	0.22	-10000	0	-0.59	143	143
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	-0.087	0.27	-10000	0	-0.66	143	143
MET	-0.14	0.32	-10000	0	-0.83	144	144
MAP4K1	-0.03	0.15	-10000	0	-0.34	144	144
PTK2	0	0	-10000	0	-10000	0	0
MAP2K2	-0.087	0.27	-10000	0	-0.66	143	143
BAD	0.012	0.023	0.46	2	-10000	0	2
MAP2K4	-0.011	0.14	-10000	0	-0.48	18	18
SHP2/GRB2/SOS1/GAB1	-0.099	0.2	-10000	0	-0.53	143	143
INPPL1	0	0	-10000	0	-10000	0	0
PXN	0	0	-10000	0	-10000	0	0
SH3KBP1	0	0	-10000	0	-10000	0	0
HGS	-0.072	0.14	-10000	0	-0.34	178	178
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.05	0.2	-10000	0	-0.84	50	50
RASA1	0	0	-10000	0	-10000	0	0
NCK1	0	0	-10000	0	-10000	0	0
PTPRJ	0	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.068	0.14	-10000	0	-0.34	143	143
PDPK1	-0.006	0.029	0.59	2	-10000	0	2
HGF/MET/SHIP	-0.13	0.25	-10000	0	-0.6	178	178

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	-0.025	0.063	-10000	0	-0.53	2	2
epithelial cell differentiation	-0.018	0.054	-10000	0	-0.45	1	1
ITCH	0.008	0.021	-10000	0	-10000	0	0
WWP1	0.009	0.067	-10000	0	-10000	0	0
FYN	-0.001	0.029	-10000	0	-0.84	1	1
EGFR	-0.29	0.4	-10000	0	-0.83	297	297
PRL	-0.004	0.032	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.11	0.22	-10000	0	-0.5	46	46
PTPRZ1	-0.45	0.42	-10000	0	-0.84	449	449
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.17	0.21	-10000	0	-0.55	53	53
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.2	0.25	-10000	0	-0.53	298	298
ADAM17	0.008	0.021	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.029	0.071	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.06	0.15	-10000	0	-0.57	52	52
NCOR1	-0.001	0.029	-10000	0	-0.84	1	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.18	0.23	-10000	0	-0.5	298	298
GRIN2B	-0.21	0.25	-10000	0	-0.5	347	347
ErbB4/ErbB2/betacellulin	-0.049	0.12	-10000	0	-0.5	45	45
STAT1	-0.006	0.04	-10000	0	-10000	0	0
HBEGF	-0.002	0.041	-10000	0	-0.84	2	2
PRLR	-0.002	0.025	-10000	0	-0.28	7	7
E4ICDs/ETO2	-0.035	0.096	-10000	0	-0.58	16	16
axon guidance	0.048	0.13	-10000	0	-0.39	1	1
NEDD4	0.008	0.021	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.004	0.026	-10000	0	-10000	0	0
CBFA2T3	-0.017	0.12	-10000	0	-0.84	16	16
ErbB4/ErbB2/HBEGF	-0.025	0.052	-10000	0	-0.47	2	2
MAPK3	-0.15	0.2	-10000	0	-0.51	50	50
STAT1 (dimer)	-0.027	0.064	-10000	0	-10000	0	0
MAPK1	-0.15	0.2	-10000	0	-0.51	50	50
JAK2	0	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.19	0.23	-10000	0	-0.5	298	298
NRG1	-0.22	0.32	-10000	0	-0.65	298	298
NRG3	-0.059	0.2	-10000	0	-0.67	74	74
NRG2	-0.44	0.42	-10000	0	-0.84	447	447
NRG4	-0.004	0.034	-10000	0	-0.28	13	13
heart development	0.048	0.13	-10000	0	-0.39	1	1
neural crest cell migration	-0.19	0.23	-10000	0	-0.5	298	298
ERBB2	0.008	0.058	-10000	0	-10000	0	0
WWOX/E4ICDs	-0.024	0.058	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.19	0.23	-10000	0	-0.49	292	292
apoptosis	0.061	0.16	0.55	57	-10000	0	57
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.3	0.26	-10000	0	-0.54	447	447
ErbB4/ErbB2/epiregulin	-0.087	0.16	-10000	0	-0.49	99	99
ErbB4/ErbB4/betacellulin/betacellulin	-0.053	0.13	-10000	0	-0.54	45	45
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.018	0.051	-10000	0	-0.44	2	2
MDM2	0.011	0.073	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.19	0.24	-10000	0	-0.5	298	298
STAT5A	0.048	0.12	-10000	0	-0.46	6	6
ErbB4/EGFR/neuregulin 1 beta	-0.35	0.38	-10000	0	-0.7	411	411
DLG4	0	0	-10000	0	-10000	0	0
GRB2/SHC	0	0.006	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.023	0.056	-10000	0	-0.5	1	1
STAT5A (dimer)	-0.019	0.058	-10000	0	-0.49	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.025	0.061	-10000	0	-0.45	4	4
LRIG1	-0.001	0.029	-10000	0	-0.84	1	1
EREG	-0.12	0.27	-10000	0	-0.62	162	162
BTC	-0.045	0.19	-10000	0	-0.81	47	47
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.048	0.13	-10000	0	-0.4	1	1
ERBB4	-0.029	0.071	-10000	0	-10000	0	0
STAT5B	-0.003	0.05	-10000	0	-0.84	3	3
YAP1	-0.009	0.038	-10000	0	-0.7	2	2
GRB2	0	0.01	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.025	0.051	-10000	0	-10000	0	0
glial cell differentiation	0.022	0.055	0.49	1	-10000	0	1
WWOX	0	0.01	-10000	0	-10000	0	0
cell proliferation	-0.12	0.24	-10000	0	-0.48	155	155

×

Calcium signaling in the CD4+ TCR pathway

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
NFATC1	0.01	0.032	-9999	-0.55	1	1
NFATC2	-0.022	0.14	-9999	-0.58	47	47
NFATC3	0.011	0.025	-9999	-10000	0	0
CD40LG	-0.27	0.33	-9999	-0.74	234	234
PTGS2	-0.38	0.43	-9999	-0.88	327	327
JUNB	0	0	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.004	0.009	-9999	-10000	0	0
CaM/Ca2+	-0.004	0.009	-9999	-10000	0	0
CALM1	0	0.002	-9999	-10000	0	0
JUN	-0.009	0.087	-9999	-0.85	9	9
mol:Ca2+	-0.006	0.009	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.006	-9999	-10000	0	0
FOSL1	-0.007	0.056	-9999	-0.84	2	2
CREM	0	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.061	0.14	-9999	-0.52	46	46
FOS	-0.28	0.4	-9999	-0.85	272	272
IFNG	-0.27	0.31	-9999	-0.7	244	244
AP-1/NFAT1-c-4	-0.32	0.39	-9999	-0.84	249	249
FASLG	-0.26	0.31	-9999	-0.7	228	228
NFAT1-c-4/ICER1	-0.042	0.12	-9999	-0.49	48	48
IL2RA	-0.26	0.31	-9999	-0.71	232	232
FKBP12/FK506	0	0.006	-9999	-10000	0	0
CSF2	-0.23	0.33	-9999	-0.69	229	229
JunB/Fra1/NFAT1-c-4	-0.04	0.12	-9999	-0.48	46	46
IL4	-0.22	0.34	-9999	-0.69	230	230
IL2	-0.012	0.025	-9999	-10000	0	0
IL3	-0.024	0.027	-9999	-10000	0	0
FKBP1A	0	0.01	-9999	-10000	0	0
BATF3	-0.001	0.029	-9999	-0.84	1	1
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.001	0.011	-9999	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.11	0.13	-10000	0	-0.34	65	65
NT3 (dimer)/TRKC	-0.32	0.39	-10000	0	-0.74	361	361
NT3 (dimer)/TRKB	-0.55	0.48	-10000	0	-0.85	537	537
SHC/Grb2/SOS1/GAB1/PI3K	0	0.001	-10000	0	-10000	0	0
RAPGEF1	0	0	-10000	0	-10000	0	0
BDNF	-0.073	0.23	-10000	0	-0.7	87	87
PIK3CA	0	0.01	-10000	0	-10000	0	0
DYNLT1	0	0.01	-10000	0	-0.28	1	1
NTRK1	-0.01	0.061	-10000	0	-0.84	2	2
NTRK2	-0.44	0.42	-10000	0	-0.84	440	440
NTRK3	-0.29	0.4	-10000	0	-0.83	297	297
NT-4/5 (dimer)/TRKB	-0.66	0.53	-10000	0	-0.95	584	584
neuron apoptosis	0.26	0.25	0.6	246	-10000	0	246
SHC 2-3/Grb2	-0.28	0.29	-10000	0	-0.68	246	246
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.26	0.3	-10000	0	-0.7	232	232
SHC3	-0.26	0.28	-10000	0	-0.6	293	293
STAT3 (dimer)	-0.005	0.029	-10000	0	-0.39	3	3
NT3 (dimer)/TRKA	-0.28	0.34	-10000	0	-0.65	353	353
RIN/GDP	-0.072	0.13	-10000	0	-0.3	40	40
GIPC1	0	0	-10000	0	-10000	0	0
KRAS	0	0.01	-10000	0	-10000	0	0
DNAJA3	-0.15	0.21	-10000	0	-0.44	277	277
RIN/GTP	0	0.009	-10000	0	-10000	0	0
CCND1	0.017	0.075	-10000	0	-1	3	3
MAGED1	-0.001	0.014	-10000	0	-10000	0	0
PTPN11	0	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.32	0.41	-10000	0	-0.84	324	324
SHC/GRB2/SOS1	0	0.005	-10000	0	-10000	0	0
GRB2	0	0.01	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.029	0.12	-10000	0	-0.58	33	33
TRKA/NEDD4-2	-0.007	0.048	-10000	0	-0.64	3	3
ELMO1	0	0	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0	0	-10000	0	-10000	0	0
NGF	-0.017	0.11	-10000	0	-0.66	22	22
HRAS	0	0.01	-10000	0	-10000	0	0
DOCK1	0	0	-10000	0	-10000	0	0
GAB2	-0.003	0.027	-10000	0	-0.28	8	8
RIT2	-0.001	0.014	-10000	0	-10000	0	0
RIT1	0	0	-10000	0	-10000	0	0
FRS2	-0.003	0.03	-10000	0	-0.28	10	10
DNM1	-0.005	0.065	-10000	0	-0.74	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.15	0.21	-10000	0	-0.43	277	277
mol:GDP	-0.11	0.19	-10000	0	-0.38	192	192
NGF (dimer)	-0.017	0.11	-10000	0	-0.66	22	22
RhoG/GDP	0	0	-10000	0	-10000	0	0
RIT1/GDP	-0.069	0.13	-10000	0	-0.3	40	40
TIAM1	-0.001	0.019	-10000	0	-0.28	4	4
PIK3R1	0	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.34	0.32	-10000	0	-0.61	463	463
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.002	0.015	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0	0.004	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.14	0.31	-10000	0	-0.84	135	135
RAP1/GDP	-0.077	0.089	-10000	0	-0.27	2	2
KIDINS220/CRKL	0	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.073	0.23	-10000	0	-0.7	87	87
ubiquitin-dependent protein catabolic process	-0.017	0.084	-10000	0	-0.56	18	18
Schwann cell development	-0.061	0.045	-10000	0	-10000	0	0
EHD4	0	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.001	0.013	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0	0.001	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.46	0.41	-10000	0	-0.71	546	546
ABL1	0	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
Rap1/GTP	-0.11	0.1	-10000	0	-10000	0	0
STAT3	-0.005	0.029	-10000	0	-0.38	3	3
axon guidance	-0.43	0.37	-10000	0	-0.66	546	546
MAPK3	-0.026	0.1	-10000	0	-0.53	33	33
MAPK1	-0.026	0.1	-10000	0	-0.53	33	33
CDC42/GDP	-0.069	0.13	-10000	0	-0.29	47	47
NTF3	-0.14	0.31	-10000	0	-0.84	135	135
NTF4	-0.32	0.41	-10000	0	-0.84	324	324
NGF (dimer)/TRKA/FAIM	-0.016	0.082	-10000	0	-0.56	17	17
PI3K	0	0.006	-10000	0	-10000	0	0
FRS3	0	0	-10000	0	-10000	0	0
FAIM	0	0	-10000	0	-10000	0	0
GAB1	0	0	-10000	0	-10000	0	0
RASGRF1	-0.17	0.22	-10000	0	-0.46	285	285
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.27	0.36	-10000	0	-0.65	362	362
RGS19	-0.001	0.014	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.007	0.084	-10000	0	-10000	0	0
Rac1/GDP	-0.069	0.13	-10000	0	-0.29	43	43
NGF (dimer)/TRKA/GRIT	-0.017	0.083	-10000	0	-0.57	17	17
neuron projection morphogenesis	-0.12	0.21	-10000	0	-0.6	17	17
NGF (dimer)/TRKA/NEDD4-2	-0.017	0.084	-10000	0	-0.56	18	18
MAP2K1	0	0.003	-10000	0	-10000	0	0
NGFR	-0.28	0.39	-10000	0	-0.84	277	277
NGF (dimer)/TRKA/GIPC/GAIP	-0.01	0.057	-10000	0	-0.35	21	21
RAS family/GTP/PI3K	0	0.002	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.011	-10000	0	-10000	0	0
NRAS	-0.001	0.014	-10000	0	-10000	0	0
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
PRKCI	0	0.01	-10000	0	-0.28	1	1
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	-0.001	0.029	-10000	0	-0.84	1	1
MAPKKK cascade	-0.068	0.12	-10000	0	-0.82	17	17
RASA1	0	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.006	0.042	-10000	0	-0.64	2	2
SQSTM1	-0.001	0.014	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.31	0.3	-10000	0	-0.56	463	463
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.014	0.071	-10000	0	-0.48	18	18
MATK	-0.02	0.12	-10000	0	-0.63	27	27
NEDD4L	-0.001	0.029	-10000	0	-0.84	1	1
RAS family/GDP	-0.07	0.083	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.16	0.22	-10000	0	-0.47	284	284
Rac1/GTP	-0.13	0.15	-10000	0	-0.35	205	205
FRS2 family/SHP2/CRK family	-0.001	0.01	-10000	0	-10000	0	0

×

Nongenotropic Androgen 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
PTK2	0.011	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.061	0.17	-10000	0	-0.52	97	97
regulation of S phase of mitotic cell cycle	-0.038	0.11	-10000	0	-0.34	92	92
GNAO1	-0.033	0.14	-10000	0	-0.84	21	21
HRAS	0	0.01	-10000	0	-10000	0	0
SHBG/T-DHT	0	0.005	-10000	0	-10000	0	0
PELP1	0	0	-10000	0	-10000	0	0
AKT1	0.011	0.003	-10000	0	-10000	0	0
MAP2K1	-0.041	0.16	-10000	0	-0.46	92	92
T-DHT/AR	-0.072	0.21	-10000	0	-0.65	93	93
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.004	-10000	0	-0.007	272	272
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.043	0.18	-10000	0	-0.84	43	43
mol:GDP	-0.069	0.2	-10000	0	-0.63	92	92
cell proliferation	-0.11	0.24	-10000	0	-0.57	82	82
PIK3CA	0	0.01	-10000	0	-10000	0	0
FOS	-0.25	0.43	-10000	0	-0.87	272	272
mol:Ca2+	-0.016	0.028	-10000	0	-0.078	111	111
MAPK3	-0.076	0.2	-10000	0	-0.51	92	92
MAPK1	-0.049	0.12	-10000	0	-0.31	48	48
PIK3R1	0	0	-10000	0	-10000	0	0
mol:IP3	-0.001	0.002	-10000	0	-0.005	272	272
cAMP biosynthetic process	0.012	0.025	-10000	0	-10000	0	0
GNG2	-0.006	0.07	-10000	0	-0.84	6	6
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.005	272	272
HRAS/GTP	-0.061	0.15	-10000	0	-0.49	92	92
actin cytoskeleton reorganization	0	0.003	-10000	0	-10000	0	0
SRC	0	0.01	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.005	272	272
PI3K	0	0.005	-10000	0	-10000	0	0
apoptosis	0.11	0.23	0.43	272	-10000	0	272
T-DHT/AR/PELP1	-0.063	0.18	-10000	0	-0.57	92	92
HRAS/GDP	-0.066	0.19	-10000	0	-0.6	92	92
CREB1	-0.12	0.25	-10000	0	-0.46	272	272
RAC1-CDC42/GTP	0	0.003	-10000	0	-10000	0	0
AR	-0.092	0.26	-10000	0	-0.84	93	93
GNB1	0	0	-10000	0	-10000	0	0
RAF1	-0.04	0.16	-10000	0	-0.48	92	92
RAC1-CDC42/GDP	-0.062	0.18	-10000	0	-0.57	92	92
T-DHT/AR/PELP1/Src	-0.058	0.16	-10000	0	-0.53	92	92
MAP2K2	-0.041	0.16	-10000	0	-0.46	92	92
T-DHT/AR/PELP1/Src/PI3K	-0.038	0.11	-10000	0	-0.35	92	92
GNAZ	-0.006	0.071	-10000	0	-0.84	6	6
SHBG	0	0.01	-10000	0	-0.28	1	1
Gi family/GNB1/GNG2/GDP	-0.036	0.1	-10000	0	-0.46	29	29
mol:T-DHT	-0.001	0.001	0.002	48	-0.003	223	271
RAC1	0	0	-10000	0	-10000	0	0
GNRH1	0.005	0.061	-10000	0	-0.66	7	7
Gi family/GTP	-0.047	0.1	-10000	0	-0.31	70	70
CDC42	0	0	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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
NFATC2	-0.047	0.19	-9999	-0.84	47	47
GNB1/GNG2	-0.16	0.24	-9999	-0.72	86	86
mol:DAG	-0.14	0.21	-9999	-0.64	86	86
PLCG1	-0.14	0.22	-9999	-0.67	86	86
YES1	-0.16	0.24	-9999	-0.69	95	95
FZD3	-0.008	0.081	-9999	-0.84	8	8
FZD6	-0.006	0.07	-9999	-0.84	6	6
G protein	-0.15	0.22	-9999	-0.67	88	88
MAP3K7	-0.079	0.19	-9999	-0.51	87	87
mol:Ca2+	-0.14	0.2	-9999	-0.61	86	86
mol:IP3	-0.14	0.21	-9999	-0.64	86	86
NLK	-0.006	0.01	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
CAMK2A	-0.094	0.21	-9999	-0.56	87	87
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.18	0.26	-9999	-0.46	322	322
CSNK1A1	0	0	-9999	-10000	0	0
GNAS	-0.16	0.24	-9999	-0.7	94	94
GO:0007205	-0.11	0.23	-9999	-0.62	86	86
WNT6	-0.18	0.34	-9999	-0.84	177	177
WNT4	-0.024	0.13	-9999	-0.84	19	19
NFAT1/CK1 alpha	-0.16	0.24	-9999	-0.66	107	107
GNG2	-0.006	0.07	-9999	-0.84	6	6
WNT5A	-0.014	0.099	-9999	-0.84	11	11
WNT11	-0.2	0.35	-9999	-0.81	203	203
CDC42	-0.12	0.25	-9999	-0.69	83	83

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.035	0.05	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.077	0.16	-9999	-0.48	65	65
JUN	-0.047	0.14	-9999	-0.56	16	16
HRAS	0	0.01	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.15	0.21	-9999	-0.56	148	148
RAP1A	0	0	-9999	-10000	0	0
FRS2	-0.003	0.03	-9999	-0.28	10	10
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.15	0.21	-9999	-0.56	145	145
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.1	0.19	-9999	-0.52	139	139
RHOA	0	0	-9999	-10000	0	0
RAP1A/GTP	-0.13	0.18	-9999	-0.5	145	145
GRB7	-0.021	0.077	-9999	-0.29	62	62
RET51/GFRalpha1/GDNF	-0.15	0.21	-9999	-0.56	148	148
MAPKKK cascade	-0.094	0.17	-9999	-0.56	35	35
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.12	0.24	-9999	-0.6	148	148
lamellipodium assembly	-0.077	0.15	-9999	-0.38	145	145
RET51/GFRalpha1/GDNF/SHC	-0.15	0.21	-9999	-0.56	148	148
PIK3CA	0	0.01	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.1	0.19	-9999	-0.52	139	139
RET9/GFRalpha1/GDNF/Shank3	-0.1	0.19	-9999	-0.52	139	139
MAPK3	-0.12	0.17	-9999	-0.47	145	145
DOK1	0	0	-9999	-10000	0	0
DOK6	-0.01	0.084	-9999	-0.84	8	8
PXN	0	0	-9999	-10000	0	0
neurite development	-0.11	0.16	-9999	-0.56	38	38
DOK5	-0.018	0.12	-9999	-0.84	16	16
GFRA1	-0.16	0.31	-9999	-0.84	139	139
MAPK8	-0.069	0.13	-9999	-0.42	35	35
HRAS/GTP	-0.098	0.2	-9999	-0.52	145	145
tube development	-0.094	0.18	-9999	-0.49	139	139
MAPK1	-0.12	0.17	-9999	-0.47	145	145
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.062	0.13	-9999	-0.35	139	139
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0	0.01	-9999	-10000	0	0
PDLIM7	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.14	0.2	-9999	-0.54	150	150
SHC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.15	0.21	-9999	-0.56	148	148
RET51/GFRalpha1/GDNF/Dok5	-0.16	0.22	-9999	-0.58	158	158
PRKCA	-0.022	0.13	-9999	-0.77	24	24
HRAS/GDP	0	0.006	-9999	-10000	0	0
CREB1	-0.068	0.15	-9999	-0.39	139	139
PIK3R1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.062	0.13	-9999	-0.35	139	139
RET51/GFRalpha1/GDNF/Grb7	-0.16	0.21	-9999	-0.58	150	150
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.12	0.16	-9999	-0.3	335	335
DOK4	0	0	-9999	-10000	0	0
JNK cascade	-0.046	0.14	-9999	-0.54	16	16
RET9/GFRalpha1/GDNF/FRS2	-0.1	0.19	-9999	-0.52	139	139
SHANK3	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.062	0.13	-9999	-0.35	139	139
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.079	0.14	-9999	-0.37	145	145
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.078	0.14	-9999	-0.37	145	145
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.08	0.15	-9999	-0.38	145	145
PI3K	-0.12	0.24	-9999	-0.61	145	145
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.094	0.18	-9999	-0.49	139	139
GRB10	0	0	-9999	-10000	0	0
activation of MAPKK activity	-0.075	0.13	-9999	-0.35	139	139
RET51/GFRalpha1/GDNF/FRS2	-0.15	0.21	-9999	-0.56	148	148
GAB1	0	0	-9999	-10000	0	0
IRS1	-0.031	0.16	-9999	-0.84	31	31
IRS2	-0.038	0.17	-9999	-0.84	38	38
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.08	0.15	-9999	-0.38	145	145
RET51/GFRalpha1/GDNF/PKC alpha	-0.17	0.22	-9999	-0.57	169	169
GRB2	0	0.01	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GDNF	-0.016	0.065	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.17	0.24	-9999	-0.63	156	156
Rac1/GTP	-0.093	0.18	-9999	-0.46	145	145
RET9/GFRalpha1/GDNF	-0.11	0.21	-9999	-0.57	143	143
GFRalpha1/GDNF	-0.13	0.24	-9999	-0.65	143	143

×

Visual signal transduction: Rods

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
mol:K +	0	0	-9999	-10000	0	0
GNAT1/GTP	-0.003	0.022	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.01	0.038	-9999	-0.3	2	2
PDE6G/GNAT1/GTP	-0.007	0.032	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.004	0.033	-9999	-0.28	12	12
GRK1	-0.003	0.027	-9999	-0.28	8	8
CNG Channel	-0.16	0.22	-9999	-0.47	264	264
mol:Na +	-0.15	0.2	-9999	-0.45	259	259
mol:ADP	-0.003	0.027	-9999	-0.28	8	8
RGS9-1/Gbeta5/R9AP	-0.071	0.18	-9999	-0.57	92	92
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.15	0.21	-9999	-0.46	259	259
CNGB1	-0.014	0.061	-9999	-10000	0	0
RDH5	-0.53	0.4	-9999	-0.84	533	533
SAG	-0.014	0.061	-9999	-10000	0	0
mol:Ca2+	-0.14	0.2	-9999	-0.43	243	243
Na + (4 Units)	-0.14	0.19	-9999	-0.42	243	243
RGS9	-0.095	0.26	-9999	-0.84	92	92
GNB1/GNGT1	-0.029	0.065	-9999	-10000	0	0
GNAT1/GDP	-0.063	0.16	-9999	-0.5	92	92
GUCY2D	-0.004	0.042	-9999	-0.33	11	11
GNGT1	-0.046	0.1	-9999	-10000	0	0
GUCY2F	-0.001	0.014	-9999	-0.28	2	2
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.017	0.073	-9999	-0.48	17	17
mol:11-cis-retinal	-0.53	0.4	-9999	-0.84	533	533
mol:cGMP	-0.011	0.049	-9999	-0.49	6	6
GNB1	0	0	-9999	-10000	0	0
Rhodopsin	-0.41	0.31	-9999	-0.65	533	533
SLC24A1	0	0	-9999	-10000	0	0
CNGA1	-0.26	0.38	-9999	-0.83	261	261
Metarhodopsin II	-0.003	0.021	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.011	0.052	-9999	-0.52	6	6
RGS9BP	-0.017	0.066	-9999	-0.28	51	51
Metarhodopsin II/Transducin	-0.008	0.018	-9999	-10000	0	0
GCAP Family/Ca ++	-0.01	0.049	-9999	-0.52	5	5
PDE6A/B	-0.017	0.094	-9999	-0.65	17	17
mol:Pi	-0.071	0.18	-9999	-0.57	92	92
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.022	0.048	-9999	-10000	0	0
PDE6B	-0.017	0.12	-9999	-0.84	17	17
PDE6A	-0.006	0.04	-9999	-10000	0	0
PDE6G	-0.01	0.051	-9999	-0.28	29	29
RHO	-0.005	0.036	-9999	-0.28	14	14
PDE6	-0.07	0.16	-9999	-0.48	105	105
GUCA1A	-0.014	0.06	-9999	-0.28	41	41
GC2/GCAP Family	-0.01	0.049	-9999	-0.52	5	5
GUCA1C	0	0.01	-9999	-10000	0	0
GUCA1B	-0.005	0.064	-9999	-0.84	5	5

×

Glypican 1 network

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.23	0.28	-10000	0	-0.56	341	341
fibroblast growth factor receptor signaling pathway	-0.23	0.28	-10000	0	-0.56	341	341
LAMA1	-0.095	0.26	-10000	0	-0.83	97	97
PRNP	-0.011	0.095	-10000	0	-0.84	11	11
GPC1/SLIT2	-0.049	0.17	-10000	0	-0.64	63	63
SMAD2	-0.014	0.081	-10000	0	-0.51	22	22
GPC1/PrPc/Cu2+	-0.008	0.065	-10000	0	-0.57	11	11
GPC1/Laminin alpha1	-0.074	0.2	-10000	0	-0.64	95	95
TDGF1	-0.019	0.12	-10000	0	-0.84	18	18
CRIPTO/GPC1	-0.015	0.094	-10000	0	-0.64	18	18
APP/GPC1	0	0.009	-10000	0	-10000	0	0
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.012	0.087	-10000	0	-0.56	19	19
FLT1	-0.001	0.029	-10000	0	-0.84	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.015	0.089	-10000	0	-0.56	22	22
SERPINC1	-0.014	0.06	-10000	0	-10000	0	0
FYN	0.012	0.087	-10000	0	-0.56	19	19
FGR	0.012	0.085	-10000	0	-0.56	18	18
positive regulation of MAPKKK cascade	0.025	0.095	-10000	0	-0.55	18	18
SLIT2	-0.063	0.22	-10000	0	-0.84	63	63
GPC1/NRG	-0.23	0.31	-10000	0	-0.64	298	298
NRG1	-0.3	0.4	-10000	0	-0.84	298	298
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.002	0.024	-10000	0	-0.56	1	1
LYN	0.012	0.085	-10000	0	-0.56	18	18
mol:Spermine	0.011	0.01	-10000	0	-0.19	2	2
cell growth	-0.23	0.28	-10000	0	-0.56	341	341
BMP signaling pathway	0.001	0.014	0.28	2	-10000	0	2
SRC	0.012	0.085	-10000	0	-0.56	18	18
TGFBR1	0	0.01	-10000	0	-0.28	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.29	0.4	-10000	0	-0.8	308	308
GPC1	-0.001	0.014	-10000	0	-0.28	2	2
TGFBR1 (dimer)	0	0.01	-10000	0	-0.28	1	1
VEGFA	-0.003	0.029	-10000	0	-0.28	9	9
BLK	-0.01	0.11	-10000	0	-0.59	20	20
HCK	0.01	0.087	-10000	0	-0.56	18	18
FGF2	-0.34	0.41	-10000	0	-0.84	337	337
FGFR1	-0.008	0.077	-10000	0	-0.71	9	9
VEGFR1 homodimer	-0.001	0.029	-10000	0	-0.84	1	1
TGFBR2	-0.022	0.13	-10000	0	-0.84	22	22
cell death	0	0.009	-10000	0	-10000	0	0
ATIII/GPC1	-0.009	0.039	-10000	0	-10000	0	0
PLA2G2A/GPC1	-0.23	0.3	-10000	0	-0.65	289	289
LCK	0	0.11	-10000	0	-0.56	29	29
neuron differentiation	-0.23	0.31	-10000	0	-0.64	298	298
PrPc/Cu2+	-0.009	0.074	-10000	0	-0.65	11	11
APP	0	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	-0.022	0.13	-10000	0	-0.84	22	22

×

IL23-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.18	0.4	-9999	-1	74	74
IL23A	-0.18	0.4	-9999	-1.1	58	58
NF kappa B1 p50/RelA/I kappa B alpha	-0.25	0.32	-9999	-0.87	119	119
positive regulation of T cell mediated cytotoxicity	-0.2	0.43	-9999	-0.87	179	179
ITGA3	-0.17	0.39	-9999	-1	73	73
IL17F	-0.11	0.29	-9999	-0.66	66	66
IL12B	-0.041	0.11	-9999	-0.3	57	57
STAT1 (dimer)	-0.23	0.38	-9999	-0.87	146	146
CD4	-0.17	0.38	-9999	-0.96	72	72
IL23	-0.19	0.38	-9999	-1.1	59	59
IL23R	-0.015	0.088	-9999	-10000	0	0
IL1B	-0.19	0.41	-9999	-1.1	75	75
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.18	0.38	-9999	-0.94	84	84
TYK2	0.011	0.016	-9999	-10000	0	0
STAT4	-0.033	0.16	-9999	-0.82	34	34
STAT3	0	0	-9999	-10000	0	0
IL18RAP	-0.034	0.16	-9999	-0.84	33	33
IL12RB1	0.001	0.06	-9999	-0.3	26	26
PIK3CA	0	0.01	-9999	-10000	0	0
IL12Rbeta1/TYK2	-0.002	0.045	-9999	-0.69	1	1
IL23R/JAK2	-0.013	0.11	-9999	-10000	0	0
positive regulation of chronic inflammatory response	-0.2	0.43	-9999	-0.87	179	179
natural killer cell activation	0.002	0.008	-9999	-10000	0	0
JAK2	0.018	0.021	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.18	0.37	-9999	-0.98	62	62
ALOX12B	-0.18	0.38	-9999	-0.9	99	99
CXCL1	-0.38	0.66	-9999	-1.4	234	234
T cell proliferation	-0.2	0.43	-9999	-0.87	179	179
NFKBIA	0	0	-9999	-10000	0	0
IL17A	-0.074	0.24	-9999	-0.54	45	45
PI3K	-0.25	0.33	-9999	-0.86	129	129
IFNG	-0.005	0.026	-9999	-0.092	18	18
STAT3 (dimer)	-0.24	0.31	-9999	-0.87	107	107
IL18R1	-0.011	0.095	-9999	-0.84	11	11
IL23/IL23R/JAK2/TYK2/SOCS3	-0.088	0.24	-9999	-0.56	43	43
IL18/IL18R	-0.033	0.13	-9999	-0.58	42	42
macrophage activation	-0.014	0.017	-9999	-0.043	60	60
TNF	-0.19	0.41	-9999	-1.1	76	76
STAT3/STAT4	-0.27	0.35	-9999	-0.88	157	157
STAT4 (dimer)	-0.24	0.4	-9999	-0.88	183	183
IL18	-0.007	0.045	-9999	-0.28	22	22
IL19	-0.18	0.38	-9999	-0.92	95	95
STAT5A (dimer)	-0.23	0.38	-9999	-0.85	165	165
STAT1	-0.006	0.04	-9999	-10000	0	0
SOCS3	-0.005	0.064	-9999	-0.84	5	5
CXCL9	-0.19	0.39	-9999	-0.95	90	90
MPO	-0.22	0.48	-9999	-1.2	110	110
positive regulation of humoral immune response	-0.2	0.43	-9999	-0.87	179	179
IL23/IL23R/JAK2/TYK2	-0.21	0.45	-9999	-0.91	174	174
IL6	-0.49	0.72	-9999	-1.4	328	328
STAT5A	-0.007	0.076	-9999	-0.84	7	7
IL2	0.002	0.031	-9999	-0.3	2	2
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.008	-9999	-10000	0	0
CD3E	-0.19	0.42	-9999	-1.1	80	80
keratinocyte proliferation	-0.2	0.43	-9999	-0.87	179	179
NOS2	-0.17	0.39	-9999	-0.98	74	74

×

Syndecan-1-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0	0	-9999	-10000	0	0
CCL5	-0.011	0.063	-9999	-0.84	2	2
SDCBP	0	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.073	0.11	-9999	-0.35	82	82
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.067	0.099	-9999	-0.36	32	32
Syndecan-1/Syntenin	-0.066	0.099	-9999	-0.36	32	32
MAPK3	-0.049	0.09	-9999	-0.52	4	4
HGF/MET	-0.15	0.29	-9999	-0.69	178	178
TGFB1/TGF beta receptor Type II	0	0	-9999	-10000	0	0
BSG	0	0	-9999	-10000	0	0
keratinocyte migration	-0.066	0.098	-9999	-0.36	32	32
Syndecan-1/RANTES	-0.072	0.11	-9999	-0.39	33	33
Syndecan-1/CD147	-0.057	0.096	-9999	-0.56	4	4
Syndecan-1/Syntenin/PIP2	-0.064	0.096	-9999	-0.35	32	32
LAMA5	0	0.01	-9999	-0.28	1	1
positive regulation of cell-cell adhesion	-0.063	0.094	-9999	-0.34	32	32
MMP7	-0.12	0.29	-9999	-0.84	116	116
HGF	-0.05	0.2	-9999	-0.84	50	50
Syndecan-1/CASK	-0.069	0.1	-9999	-0.33	82	82
Syndecan-1/HGF/MET	-0.17	0.26	-9999	-0.61	180	180
regulation of cell adhesion	-0.036	0.093	-9999	-0.54	3	3
HPSE	-0.008	0.056	-9999	-0.84	2	2
positive regulation of cell migration	-0.073	0.11	-9999	-0.35	82	82
SDC1	-0.073	0.11	-9999	-0.35	82	82
Syndecan-1/Collagen	-0.073	0.11	-9999	-0.35	82	82
PPIB	0	0.01	-9999	-10000	0	0
MET	-0.14	0.32	-9999	-0.83	144	144
PRKACA	0	0	-9999	-10000	0	0
MMP9	-0.12	0.14	-9999	-0.28	352	352
MAPK1	-0.049	0.09	-9999	-0.52	4	4
homophilic cell adhesion	-0.072	0.11	-9999	-0.34	82	82
MMP1	-0.22	0.11	-9999	-0.28	662	662

×

Aurora C signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.072	0.064	-9999	-0.64	1	1
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.019	0.017	-9999	-10000	0	0
AURKB	-0.16	0.14	-9999	-0.28	492	492
AURKC	-0.005	0.045	-9999	-0.84	1	1

×

IL6-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.055	0.21	-9999	-0.64	39	39
CRP	-0.059	0.21	-9999	-0.64	39	39
cell cycle arrest	-0.072	0.24	-9999	-0.72	45	45
TIMP1	-0.054	0.2	-9999	-0.58	36	36
IL6ST	-0.042	0.21	-9999	-0.82	56	56
Rac1/GDP	-0.14	0.19	-9999	-0.65	54	54
AP1	-0.14	0.25	-9999	-0.49	266	266
GAB2	-0.002	0.027	-9999	-0.28	8	8
TNFSF11	-0.065	0.22	-9999	-0.64	39	39
HSP90B1	0.017	0.047	-9999	-10000	0	0
GAB1	0	0.002	-9999	-10000	0	0
MAPK14	-0.12	0.24	-9999	-0.73	55	55
AKT1	0.041	0.026	-9999	-10000	0	0
FOXO1	0.052	0.044	-9999	-0.44	6	6
MAP2K6	-0.14	0.24	-9999	-0.58	100	100
mol:GTP	0	0.001	-9999	-10000	0	0
MAP2K4	-0.075	0.22	-9999	-0.63	52	52
MITF	-0.13	0.24	-9999	-0.51	124	124
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0	0	-9999	-10000	0	0
A2M	0.016	0.11	-9999	-1.5	4	4
CEBPB	0.015	0.007	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.052	0.069	-9999	-0.27	7	7
STAT3	-0.08	0.26	-9999	-0.78	45	45
STAT1	-0.012	0.023	-9999	-10000	0	0
CEBPD	-0.057	0.22	-9999	-0.67	39	39
PIK3CA	0.01	0.011	-9999	-10000	0	0
PI3K	0	0.006	-9999	-10000	0	0
JUN	-0.009	0.086	-9999	-0.84	9	9
PIAS3/MITF	-0.14	0.2	-9999	-0.66	56	56
MAPK11	-0.12	0.24	-9999	-0.75	55	55
STAT3 (dimer)/FOXO1	-0.022	0.21	-9999	-0.57	42	42
GRB2/SOS1/GAB family	-0.13	0.18	-9999	-0.72	37	37
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.15	0.24	-9999	-0.38	365	365
GRB2	0	0.01	-9999	-10000	0	0
JAK2	0	0	-9999	-10000	0	0
LBP	-0.23	0.45	-9999	-0.96	210	210
PIK3R1	0	0	-9999	-10000	0	0
JAK1	0	0.002	-9999	-10000	0	0
MYC	-0.07	0.26	-9999	-0.87	44	44
FGG	-0.064	0.22	-9999	-0.65	39	39
macrophage differentiation	-0.072	0.24	-9999	-0.72	45	45
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.22	0.28	-9999	-0.52	366	366
JUNB	-0.054	0.21	-9999	-0.61	40	40
FOS	-0.27	0.39	-9999	-0.84	272	272
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.14	0.25	-9999	-0.38	364	364
STAT1/PIAS1	-0.14	0.2	-9999	-0.45	148	148
GRB2/SOS1/GAB family/SHP2/PI3K	0.001	0.009	-9999	-10000	0	0
STAT3 (dimer)	-0.076	0.25	-9999	-0.76	44	44
PRKCD	-0.05	0.21	-9999	-0.61	48	48
IL6R	-0.022	0.13	-9999	-0.84	22	22
SOCS3	-0.11	0.23	-9999	-0.79	46	46
gp130 (dimer)/JAK1/JAK1/LMO4	-0.03	0.14	-9999	-0.56	58	58
Rac1/GTP	-0.14	0.19	-9999	-0.63	59	59
HCK	-0.004	0.033	-9999	-10000	0	0
MAPKKK cascade	0	0.068	-9999	-10000	0	0
bone resorption	-0.062	0.21	-9999	-0.61	40	40
IRF1	-0.055	0.21	-9999	-0.64	37	37
mol:GDP	-0.12	0.23	-9999	-0.46	155	155
SOS1	0	0.002	-9999	-10000	0	0
VAV1	-0.12	0.24	-9999	-0.47	154	154
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.16	0.22	-9999	-0.8	51	51
PTPN11	-0.013	0.02	-9999	-10000	0	0
IL6/IL6RA	-0.26	0.33	-9999	-0.66	332	332
gp130 (dimer)/TYK2/TYK2/LMO4	-0.032	0.14	-9999	-0.56	58	58
gp130 (dimer)/JAK2/JAK2/LMO4	-0.032	0.14	-9999	-0.56	58	58
IL6	-0.31	0.41	-9999	-0.83	324	324
PIAS3	0	0	-9999	-10000	0	0
PTPRE	0.002	0.03	-9999	-0.84	1	1
PIAS1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.17	0.23	-9999	-0.39	365	365
LMO4	0.008	0.057	-9999	-0.46	9	9
STAT3 (dimer)/PIAS3	-0.14	0.2	-9999	-0.78	44	44
MCL1	0.054	0.014	-9999	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.099	0.19	-10000	0	-0.5	146	146
ER alpha/Gai/GDP/Gbeta gamma	-0.086	0.19	-10000	0	-0.48	125	125
AKT1	-0.11	0.3	-10000	0	-0.85	117	117
PIK3CA	0	0.01	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.12	0.3	-10000	0	-0.86	117	117
mol:Ca2+	-0.023	0.14	-10000	0	-0.49	56	56
IGF1R	-0.02	0.12	-10000	0	-0.84	16	16
E2/ER alpha (dimer)/Striatin	-0.098	0.2	-10000	0	-0.57	117	117
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	0.081	0.29	0.81	117	-10000	0	117
RhoA/GTP	-0.069	0.14	-10000	0	-0.42	117	117
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.087	0.21	-10000	0	-0.56	122	122
regulation of stress fiber formation	0.014	0.13	0.41	2	-10000	0	2
E2/ERA-ERB (dimer)	-0.11	0.21	-10000	0	-0.58	141	141
KRAS	0	0.01	-10000	0	-10000	0	0
G13/GTP	-0.09	0.18	-10000	0	-0.52	117	117
pseudopodium formation	-0.014	0.13	-10000	0	-0.41	2	2
E2/ER alpha (dimer)/PELP1	-0.098	0.2	-10000	0	-0.57	117	117
GRB2	0	0.01	-10000	0	-10000	0	0
GNG2	-0.006	0.07	-10000	0	-0.84	6	6
GNAO1	-0.033	0.14	-10000	0	-0.84	21	21
HRAS	0	0.01	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.055	0.22	-10000	0	-0.55	125	125
E2/ER beta (dimer)	-0.019	0.11	-10000	0	-0.65	25	25
mol:GDP	-0.086	0.21	-10000	0	-0.55	141	141
mol:NADP	-0.055	0.22	-10000	0	-0.55	125	125
PIK3R1	0	0	-10000	0	-10000	0	0
mol:IP3	-0.025	0.15	-10000	0	-0.51	56	56
IGF-1R heterotetramer	-0.02	0.12	-10000	0	-0.84	16	16
PLCB1	-0.059	0.14	-10000	0	-0.53	55	55
PLCB2	-0.033	0.088	-10000	0	-0.67	9	9
IGF1	-0.18	0.35	-10000	0	-0.84	186	186
mol:L-citrulline	-0.055	0.22	-10000	0	-0.55	125	125
RHOA	0	0	-10000	0	-10000	0	0
Gai/GDP	-0.039	0.15	-10000	0	-0.84	21	21
JNK cascade	-0.019	0.11	-10000	0	-0.65	25	25
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	-0.025	0.14	-10000	0	-0.84	25	25
GNAQ	-0.002	0.041	-10000	0	-0.84	2	2
ESR1	-0.15	0.29	-10000	0	-0.56	228	228
Gq family/GDP/Gbeta gamma	-0.004	0.061	-10000	0	-0.54	7	7
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.022	0.13	-10000	0	-0.36	12	12
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.087	0.21	-10000	0	-0.56	122	122
GNAZ	-0.006	0.07	-10000	0	-0.84	6	6
E2/ER alpha (dimer)	-0.12	0.22	-10000	0	-0.65	117	117
STRN	0	0	-10000	0	-10000	0	0
GNAL	-0.19	0.35	-10000	0	-0.84	190	190
PELP1	0	0	-10000	0	-10000	0	0
MAPK11	-0.001	0.11	-10000	0	-0.58	26	26
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.043	0.18	-10000	0	-0.84	43	43
HBEGF	-0.063	0.19	-10000	0	-0.45	127	127
cAMP biosynthetic process	-0.2	0.27	-10000	0	-0.54	291	291
SRC	-0.047	0.19	-10000	0	-0.45	125	125
PI3K	0	0.006	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.077	0.19	-10000	0	-0.48	146	146
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.15	0.23	-10000	0	-0.53	181	181
Gs family/GTP	-0.2	0.28	-10000	0	-0.56	291	291
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.008	-10000	0	-10000	0	0
vasodilation	-0.051	0.21	-10000	0	-0.52	125	125
mol:DAG	-0.025	0.15	-10000	0	-0.51	56	56
Gs family/GDP/Gbeta gamma	-0.16	0.24	-10000	0	-0.46	292	292
MSN	-0.016	0.14	-10000	0	-0.45	2	2
Gq family/GTP	-0.036	0.092	-10000	0	-0.67	9	9
mol:PI-3-4-5-P3	-0.087	0.3	-10000	0	-0.82	117	117
NRAS	-0.001	0.014	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.051	0.21	0.52	125	-10000	0	125
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
RhoA/GDP	-0.079	0.2	-10000	0	-0.52	141	141
NOS3	-0.06	0.23	-10000	0	-0.58	125	125
GNA11	0	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.054	0.25	-10000	0	-0.66	117	117
E2/ER alpha (dimer)/PELP1/Src	-0.092	0.22	-10000	0	-0.59	122	122
ruffle organization	-0.014	0.13	-10000	0	-0.41	2	2
ROCK2	-0.064	0.13	-10000	0	-0.47	3	3
GNA14	-0.013	0.082	-10000	0	-0.4	27	27
GNA15	-0.002	0.035	-10000	0	-0.39	5	5
GNA13	0	0	-10000	0	-10000	0	0
MMP9	-0.087	0.19	-10000	0	-0.48	130	130
MMP2	-0.04	0.19	-10000	0	-0.67	23	23

×

Aurora B signaling

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
Condensin I complex	-0.055	0.054	-9999	-10000	0	0
STMN1	-0.1	0.12	-9999	-0.35	65	65
Aurora B/RasGAP/Survivin	-0.18	0.12	-9999	-10000	0	0
Chromosomal passenger complex/Cul3 protein complex	-0.15	0.15	-9999	-0.33	330	330
BIRC5	-0.21	0.12	-9999	-10000	0	0
DES	-0.31	0.34	-9999	-0.65	414	414
Aurora C/Aurora B/INCENP	-0.065	0.073	-9999	-0.65	1	1
Aurora B/TACC1	-0.09	0.11	-9999	-0.63	20	20
Aurora B/PP2A	-0.094	0.091	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.006	0.015	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.003	0.003	-9999	-10000	0	0
NDC80	-0.21	0.16	-9999	-0.35	451	451
Cul3 protein complex	-0.22	0.27	-9999	-0.56	330	330
KIF2C	-0.036	0.025	-9999	-10000	0	0
PEBP1	0	0	-9999	-10000	0	0
KIF20A	-0.23	0.11	-9999	-0.28	676	676
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.094	0.091	-9999	-10000	0	0
SEPT1	-0.004	0.034	-9999	-0.28	13	13
SMC2	0	0	-9999	-10000	0	0
SMC4	-0.006	0.039	-9999	-0.28	17	17
NSUN2/NPM1/Nucleolin	0.013	0.014	-9999	-10000	0	0
PSMA3	0	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.003	0.002	-9999	-10000	0	0
H3F3B	-0.031	0.04	-9999	-10000	0	0
AURKB	-0.16	0.15	-9999	-0.28	339	339
AURKC	-0.005	0.045	-9999	-0.84	1	1
CDCA8	-0.1	0.14	-9999	-10000	0	0
cytokinesis	-0.11	0.066	-9999	-10000	0	0
Aurora B/Septin1	-0.088	0.076	-9999	-10000	0	0
AURKA	-0.14	0.14	-9999	-10000	0	0
INCENP	0.001	0.003	-9999	-10000	0	0
KLHL13	-0.33	0.41	-9999	-0.84	330	330
BUB1	-0.21	0.12	-9999	-10000	0	0
hSgo1/Aurora B/Survivin	-0.25	0.17	-9999	-0.39	455	455
EVI5	0.007	0.005	-9999	-10000	0	0
RhoA/GTP	-0.094	0.092	-9999	-10000	0	0
SGOL1	-0.19	0.13	-9999	-10000	0	0
CENPA	-0.05	0.052	-9999	-10000	0	0
NCAPG	-0.16	0.14	-9999	-10000	0	0
Aurora B/HC8 Proteasome	-0.094	0.091	-9999	-10000	0	0
NCAPD2	-0.003	0.027	-9999	-0.28	8	8
Aurora B/PP1-gamma	-0.094	0.091	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
NCAPH	-0.12	0.14	-9999	-0.28	363	363
NPM1	-0.012	0.019	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
KLHL9	-0.001	0.029	-9999	-0.84	1	1
mitotic prometaphase	-0.006	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.094	0.091	-9999	-10000	0	0
PPP1CC	0	0	-9999	-10000	0	0
Centraspindlin	-0.11	0.1	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.012	0.019	-9999	-10000	0	0
MYLK	-0.073	0.14	-9999	-0.48	80	80
KIF23	-0.094	0.13	-9999	-0.28	281	281
VIM	-0.091	0.1	-9999	-0.72	2	2
RACGAP1	-0.013	0.063	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	-0.012	0.019	-9999	-10000	0	0
Chromosomal passenger complex	-0.077	0.062	-9999	-10000	0	0
Chromosomal passenger complex/EVI5	-0.15	0.17	-9999	-10000	0	0
TACC1	-0.02	0.13	-9999	-0.84	20	20
PPP2R5D	0	0	-9999	-10000	0	0
CUL3	0	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Signaling events mediated by PTP1B

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.002	0.041	-10000	0	-0.84	2	2
Jak2/Leptin Receptor	-0.15	0.24	-10000	0	-0.55	202	202
PTP1B/AKT1	-0.067	0.099	-10000	0	-0.32	84	84
FYN	-0.001	0.029	-10000	0	-0.84	1	1
p210 bcr-abl/PTP1B	-0.068	0.12	-10000	0	-0.37	86	86
EGFR	-0.3	0.4	-10000	0	-0.84	294	294
EGF/EGFR	-0.3	0.32	-10000	0	-0.6	410	410
CSF1	-0.003	0.05	-10000	0	-0.84	3	3
AKT1	0	0	-10000	0	-10000	0	0
INSR	0	0.01	-10000	0	-0.28	1	1
PTP1B/N-cadherin	-0.094	0.12	-10000	0	-0.36	88	88
Insulin Receptor/Insulin	-0.047	0.073	-10000	0	-0.4	7	7
HCK	-0.004	0.033	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
TYK2	-0.057	0.12	-10000	0	-0.35	84	84
EGF	-0.17	0.34	-10000	0	-0.85	167	167
YES1	-0.001	0.029	-10000	0	-0.84	1	1
CAV1	-0.17	0.24	-10000	0	-0.51	214	214
TXN	0	0.01	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.083	0.14	-10000	0	-0.41	93	93
cell migration	0.068	0.12	0.37	86	-10000	0	86
STAT3	0	0	-10000	0	-10000	0	0
PRLR	-0.001	0.026	-10000	0	-0.28	7	7
ITGA2B	-0.017	0.078	-10000	0	-0.84	3	3
CSF1R	0	0	-10000	0	-10000	0	0
Prolactin Receptor/Prolactin	-0.003	0.027	-10000	0	-10000	0	0
FGR	0	0.01	-10000	0	-0.28	1	1
PTP1B/p130 Cas	-0.072	0.11	-10000	0	-0.35	84	84
Crk/p130 Cas	-0.066	0.1	-10000	0	-0.41	21	21
DOK1	-0.043	0.11	-10000	0	-0.32	65	65
JAK2	-0.038	0.07	-10000	0	-0.3	7	7
Jak2/Leptin Receptor/Leptin	-0.39	0.18	-10000	0	-0.52	421	421
PIK3R1	0	0	-10000	0	-10000	0	0
PTPN1	-0.069	0.12	-10000	0	-0.38	86	86
LYN	0	0	-10000	0	-10000	0	0
CDH2	-0.058	0.12	-10000	0	-0.84	2	2
SRC	-0.013	0.046	-10000	0	-10000	0	0
ITGB3	-0.015	0.11	-10000	0	-0.84	14	14
CAT1/PTP1B	-0.086	0.17	-10000	0	-0.44	76	76
CAPN1	0	0.002	-10000	0	-10000	0	0
CSK	0	0	-10000	0	-10000	0	0
PI3K	-0.037	0.064	-10000	0	-0.42	2	2
mol:H2O2	-0.005	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.34	0.16	-10000	0	-0.45	410	410
negative regulation of transcription	-0.038	0.069	-10000	0	-0.3	7	7
FCGR2A	0	0.01	-10000	0	-10000	0	0
FER	-0.006	0.071	-10000	0	-0.85	6	6
alphaIIb/beta3 Integrin	-0.023	0.1	-10000	0	-0.66	17	17
BLK	-0.036	0.1	-10000	0	-0.3	102	102
Insulin Receptor/Insulin/Shc	0	0.005	-10000	0	-10000	0	0
RHOA	0	0.002	-10000	0	-10000	0	0
LEPR	-0.19	0.36	-10000	0	-0.84	201	201
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0	0.01	-10000	0	-10000	0	0
mol:NADPH	-0.005	0.005	-10000	0	-10000	0	0
TRPV6	-0.036	0.13	-10000	0	-0.44	18	18
PRL	-0.004	0.032	-10000	0	-10000	0	0
SOCS3	0.016	0.12	-10000	0	-1.5	5	5
SPRY2	-0.096	0.27	-10000	0	-0.85	95	95
Insulin Receptor/Insulin/IRS1	-0.021	0.11	-10000	0	-0.58	31	31
CSF1/CSF1R	-0.068	0.1	-10000	0	-0.35	75	75
Ras protein signal transduction	0.036	0.035	-10000	0	-10000	0	0
IRS1	-0.031	0.16	-10000	0	-0.84	31	31
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.68	0.32	-10000	0	-0.84	687	687
STAT5B	-0.056	0.1	-10000	0	-0.31	85	85
STAT5A	-0.057	0.1	-10000	0	-0.31	87	87
GRB2	0	0.01	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.074	0.11	-10000	0	-0.36	86	86
CSN2	0.02	0.029	-10000	0	-10000	0	0
PIK3CA	0	0.01	-10000	0	-10000	0	0
LAT	-0.014	0.054	-10000	0	-0.59	2	2
YBX1	-0.002	0.015	-10000	0	-0.27	1	1
LCK	-0.019	0.1	-10000	0	-0.46	34	34
SHC1	0	0	-10000	0	-10000	0	0
NOX4	-0.003	0.04	-10000	0	-0.85	1	1

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	-0.023	0.062	-9999	-0.6	8	8
alphaM/beta2 Integrin/GPIbA	-0.024	0.06	-9999	-0.57	7	7
alphaM/beta2 Integrin/proMMP-9	-0.076	0.077	-9999	-0.44	3	3
PLAUR	-0.021	0.073	-9999	-0.28	63	63
HMGB1	-0.014	0.018	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.018	0.026	-9999	-10000	0	0
AGER	-0.016	0.048	-9999	-0.71	3	3
RAP1A	0	0	-9999	-10000	0	0
SELPLG	0	0	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.078	0.099	-9999	-0.73	2	2
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.12	0.14	-9999	-0.28	352	352
CYR61	-0.047	0.19	-9999	-0.84	47	47
TLN1	0	0	-9999	-10000	0	0
Rap1/GTP	-0.06	0.12	-9999	-0.55	20	20
RHOA	0	0	-9999	-10000	0	0
P-selectin oligomer	-0.21	0.36	-9999	-0.84	208	208
MYH2	-0.074	0.17	-9999	-0.53	41	41
MST1R	-0.011	0.089	-9999	-0.84	9	9
leukocyte activation during inflammatory response	-0.33	0.24	-9999	-0.5	542	542
APOB	-0.54	0.4	-9999	-0.84	542	542
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.008	0.081	-9999	-0.84	8	8
JAM3	-0.003	0.05	-9999	-0.84	3	3
GP1BA	-0.011	0.08	-9999	-0.43	22	22
alphaM/beta2 Integrin/CTGF	-0.024	0.068	-9999	-0.63	9	9
alphaM/beta2 Integrin	-0.075	0.14	-9999	-0.38	77	77
JAM3 homodimer	-0.003	0.05	-9999	-0.84	3	3
ICAM2	-0.005	0.064	-9999	-0.84	5	5
ICAM1	-0.004	0.032	-9999	-10000	0	0
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.066	0.14	-9999	-0.38	77	77
cell adhesion	-0.024	0.06	-9999	-0.57	7	7
NFKB1	-0.14	0.18	-9999	-0.65	12	12
THY1	-0.002	0.023	-9999	-0.28	6	6
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.37	0.28	-9999	-0.57	542	542
alphaM/beta2 Integrin/LRP/tPA	-0.033	0.11	-9999	-0.58	31	31
IL6	-0.33	0.5	-9999	-0.96	323	323
ITGB2	-0.017	0.033	-9999	-0.34	1	1
elevation of cytosolic calcium ion concentration	-0.024	0.047	-9999	-10000	0	0
alphaM/beta2 Integrin/JAM2/JAM3	-0.04	0.12	-9999	-0.55	45	45
JAM2	-0.043	0.18	-9999	-0.84	43	43
alphaM/beta2 Integrin/ICAM1	-0.022	0.082	-9999	-0.53	19	19
alphaM/beta2 Integrin/uPA/Plg	-0.02	0.032	-9999	-10000	0	0
RhoA/GTP	-0.093	0.17	-9999	-0.41	153	153
positive regulation of phagocytosis	-0.052	0.095	-9999	-0.48	17	17
Ron/MSP	-0.017	0.1	-9999	-0.67	19	19
alphaM/beta2 Integrin/uPAR/uPA	-0.024	0.047	-9999	-10000	0	0
alphaM/beta2 Integrin/uPAR	-0.028	0.044	-9999	-10000	0	0
PLAU	-0.009	0.048	-9999	-0.28	26	26
PLAT	-0.026	0.14	-9999	-0.78	28	28
actin filament polymerization	-0.071	0.16	-9999	-0.44	63	63
MST1	-0.011	0.096	-9999	-0.84	11	11
alphaM/beta2 Integrin/lipoprotein(a)	-0.34	0.24	-9999	-0.51	542	542
TNF	-0.096	0.22	-9999	-0.95	14	14
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.022	0.035	-9999	-10000	0	0
fibrinolysis	-0.02	0.032	-9999	-10000	0	0
HCK	-0.004	0.033	-9999	-10000	0	0
dendritic cell antigen processing and presentation	-0.066	0.14	-9999	-0.38	77	77
VTN	-0.023	0.09	-9999	-0.32	61	61
alphaM/beta2 Integrin/CYR61	-0.05	0.14	-9999	-0.61	47	47
LPA	-0.002	0.021	-9999	-0.28	5	5
LRP1	-0.009	0.086	-9999	-0.84	9	9
cell migration	-0.067	0.082	-9999	-0.55	9	9
FN1	-0.12	0.14	-9999	-10000	0	0
alphaM/beta2 Integrin/Thy1	-0.019	0.028	-9999	-10000	0	0
MPO	-0.06	0.22	-9999	-0.84	60	60
KNG1	-0.004	0.033	-9999	-10000	0	0
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.069	0.17	-9999	-0.47	56	56
ELA2	0	0	-9999	-10000	0	0
PLG	-0.002	0.021	-9999	-10000	0	0
CTGF	-0.01	0.087	-9999	-0.84	9	9
alphaM/beta2 Integrin/Hck	-0.02	0.032	-9999	-10000	0	0
ITGAM	-0.015	0.027	-9999	-0.34	2	2
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.14	0.23	-9999	-0.54	208	208
HP	-0.17	0.33	-9999	-0.75	189	189
leukocyte adhesion	-0.076	0.13	-9999	-0.6	28	28
SELP	-0.21	0.36	-9999	-0.84	208	208

×

Ephrin A reverse signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.057	0.17	-9999	-0.57	83	83
EFNA5	-0.083	0.25	-9999	-0.84	83	83
FYN	-0.052	0.16	-9999	-0.52	83	83
neuron projection morphogenesis	-0.057	0.17	-9999	-0.57	83	83
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.057	0.17	-9999	-0.57	83	83
EPHA5	-0.001	0.019	-9999	-10000	0	0

×

Signaling events mediated by PRL

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
CCNE1	-0.054	0.11	-9999	-0.28	163	163
mol:Halofuginone	0	0.002	-9999	-10000	0	0
ITGA1	-0.002	0.041	-9999	-0.84	2	2
CDKN1A	-0.064	0.093	-9999	-0.88	1	1
PRL-3/alpha Tubulin	-0.001	0.012	-9999	-10000	0	0
mol:Ca2+	-0.036	0.1	-9999	-0.66	13	13
AGT	-0.051	0.14	-9999	-0.34	128	128
CCNA2	-0.19	0.26	-9999	-0.53	287	287
TUBA1B	0	0	-9999	-10000	0	0
EGR1	-0.2	0.32	-9999	-0.64	287	287
CDK2/Cyclin E1	-0.071	0.091	-9999	-0.79	1	1
MAPK3	0.021	0.014	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0.009	-9999	-10000	0	0
MAPK1	0.021	0.014	-9999	-10000	0	0
PTP4A1	-0.15	0.25	-9999	-0.5	287	287
PTP4A3	-0.001	0.019	-9999	-10000	0	0
PTP4A2	-0.001	0.014	-9999	-0.28	2	2
ITGB1	0.021	0.014	-9999	-10000	0	0
SRC	0	0.01	-9999	-10000	0	0
RAC1	-0.064	0.088	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.16	0.22	-9999	-0.46	287	287
RABGGTA	0	0	-9999	-10000	0	0
BCAR1	0	0.006	-9999	-10000	0	0
RHOC	-0.064	0.088	-9999	-10000	0	0
RHOA	-0.064	0.088	-9999	-10000	0	0
cell motility	-0.044	0.11	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.16	0.22	-9999	-0.46	287	287
PRL-3/alpha1 Integrin	-0.002	0.034	-9999	-0.64	2	2
ROCK1	-0.044	0.11	-9999	-10000	0	0
RABGGTB	0	0	-9999	-10000	0	0
CDK2	0	0	-9999	-10000	0	0
mitosis	-0.14	0.25	-9999	-0.49	287	287
ATF5	-0.001	0.019	-9999	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.003	0.036	-9999	-0.64	2	2
alphaV beta3 Integrin	-0.23	0.28	-9999	-0.57	343	343
PTK2	-0.086	0.18	-9999	-0.67	17	17
IGF1R	-0.02	0.12	-9999	-0.84	16	16
PI4KB	0	0	-9999	-10000	0	0
MFGE8	-0.012	0.094	-9999	-0.63	16	16
SRC	0	0.01	-9999	-10000	0	0
CDKN1B	-0.088	0.12	-9999	-0.94	7	7
VEGFA	-0.003	0.029	-9999	-0.28	9	9
ILK	-0.085	0.11	-9999	-0.84	4	4
ROCK1	0	0	-9999	-10000	0	0
AKT1	-0.075	0.099	-9999	-0.78	4	4
PTK2B	-0.01	0.069	-9999	-0.5	15	15
alphaV/beta3 Integrin/JAM-A	-0.21	0.25	-9999	-0.5	345	345
CBL	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.011	0.073	-9999	-0.56	14	14
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.14	0.26	-9999	-0.58	204	204
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.006	0.043	-9999	-0.43	2	2
alphaV/beta3 Integrin/Syndecan-1	-0.02	0.08	-9999	-0.56	15	15
PI4KA	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.34	0.36	-9999	-0.78	273	273
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0	0.01	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.048	0.093	-9999	-0.58	14	14
RPS6KB1	-0.31	0.33	-9999	-0.71	273	273
TLN1	0	0	-9999	-10000	0	0
MAPK3	-0.34	0.39	-9999	-0.79	343	343
GPR124	-0.008	0.081	-9999	-0.84	8	8
MAPK1	-0.34	0.39	-9999	-0.79	343	343
PXN	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.12	0.23	-9999	-0.56	178	178
cell adhesion	-0.016	0.086	-9999	-0.5	24	24
ANGPTL3	-0.002	0.021	-9999	-0.28	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	-0.003	0.031	-9999	-0.56	2	2
IGF-1R heterotetramer	-0.02	0.12	-9999	-0.84	16	16
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	-0.022	0.13	-9999	-0.84	22	22
ITGB3	-0.015	0.11	-9999	-0.84	14	14
IGF1	-0.18	0.35	-9999	-0.84	186	186
RAC1	0	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.015	0.098	-9999	-0.63	19	19
apoptosis	0	0	-9999	-10000	0	0
CD47	-0.001	0.029	-9999	-0.84	1	1
alphaV/beta3 Integrin/CD47	-0.011	0.074	-9999	-0.56	15	15
VCL	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.027	0.14	-9999	-0.7	29	29
CSF1	-0.003	0.05	-9999	-0.84	3	3
PIK3C2A	-0.085	0.11	-9999	-0.84	4	4
PI4 Kinase/Pyk2	-0.17	0.21	-9999	-0.59	42	42
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.011	0.074	-9999	-0.54	15	15
FAK1/Vinculin	-0.064	0.15	-9999	-0.51	16	16
alphaV beta3/Integrin/ppsTEM5	-0.015	0.099	-9999	-0.64	19	19
RHOA	0	0	-9999	-10000	0	0
VTN	-0.023	0.09	-9999	-0.32	61	61
BCAR1	0	0	-9999	-10000	0	0
FGF2	-0.34	0.41	-9999	-0.84	337	337
F11R	-0.24	0.33	-9999	-0.64	337	337
alphaV/beta3 Integrin/Lactadherin	-0.017	0.097	-9999	-0.58	23	23
alphaV/beta3 Integrin/TGFBR2	-0.024	0.13	-9999	-0.64	31	31
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.002	0.03	-9999	-0.51	3	3
HSP90AA1	0	0.01	-9999	-0.28	1	1
alphaV/beta3 Integrin/Talin	-0.009	0.067	-9999	-0.52	14	14
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.12	0.14	-9999	-10000	0	0
alphaV/beta3 Integrin/Pyk2	-0.01	0.07	-9999	-0.51	15	15
SDC1	-0.02	0.075	-9999	-0.29	58	58
VAV3	-0.005	0.042	-9999	-0.47	6	6
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.031	0.16	-9999	-0.84	31	31
FAK1/Paxillin	-0.064	0.15	-9999	-0.51	16	16
cell migration	-0.05	0.14	-9999	-0.45	16	16
ITGAV	0	0	-9999	-10000	0	0
PI3K	-0.19	0.22	-9999	-0.45	345	345
SPP1	-0.08	0.13	-9999	-10000	0	0
KDR	-0.002	0.041	-9999	-0.84	2	2
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0	0	-9999	-10000	0	0
COL4A3	-0.17	0.33	-9999	-0.84	166	166
angiogenesis	-0.3	0.39	-9999	-0.76	345	345
Rac1/GTP	-0.005	0.038	-9999	-0.43	6	6
EDIL3	-0.028	0.14	-9999	-0.84	23	23
cell proliferation	-0.024	0.12	-9999	-0.64	31	31

×

LPA receptor mediated 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
GNB1/GNG2	-0.013	0.083	-9999	-0.55	17	17
NF kappa B1 p50/RelA/I kappa B alpha	-0.045	0.12	-9999	-0.42	12	12
AP1	-0.21	0.28	-9999	-0.52	339	339
mol:PIP3	-0.2	0.25	-9999	-0.49	294	294
AKT1	-0.009	0.054	-9999	-0.57	2	2
PTK2B	0.015	0.058	-9999	-0.31	14	14
RHOA	0.029	0.025	-9999	-10000	0	0
PIK3CB	0	0	-9999	-10000	0	0
mol:Ca2+	-0.009	0.14	-9999	-0.37	101	101
MAGI3	-0.001	0.029	-9999	-0.84	1	1
RELA	0	0	-9999	-10000	0	0
apoptosis	-0.063	0.16	-9999	-0.45	109	109
HRAS/GDP	0	0.006	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.019	0.15	-9999	-0.44	88	88
NF kappa B1 p50/RelA	-0.054	0.14	-9999	-0.52	17	17
endothelial cell migration	0.01	0.11	-9999	-0.69	20	20
ADCY4	0.001	0.14	-9999	-0.62	26	26
ADCY5	-0.068	0.18	-9999	-0.6	54	54
ADCY6	0.01	0.12	-9999	-0.6	19	19
ADCY7	0.01	0.12	-9999	-0.6	19	19
ADCY1	0.002	0.13	-9999	-0.61	23	23
ADCY2	-0.01	0.15	-9999	-0.62	31	31
ADCY3	0.01	0.12	-9999	-0.6	19	19
ADCY8	0.007	0.12	-9999	-0.6	19	19
ADCY9	0.01	0.12	-9999	-0.6	19	19
GSK3B	0.022	0.056	-9999	-0.4	5	5
arachidonic acid secretion	0.014	0.12	-9999	-0.57	19	19
GNG2	-0.006	0.07	-9999	-0.84	6	6
TRIP6	-0.001	0.019	-9999	-0.53	1	1
GNAO1	-0.005	0.12	-9999	-0.53	40	40
HRAS	0	0.01	-9999	-10000	0	0
NFKBIA	-0.005	0.16	-9999	-0.42	101	101
GAB1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.001	0.033	-9999	-0.95	1	1
JUN	-0.009	0.086	-9999	-0.84	9	9
LPA/LPA2/NHERF2	-0.001	0.011	-9999	-10000	0	0
TIAM1	-0.001	0.04	-9999	-1.1	1	1
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	-0.01	0.14	-9999	-0.38	101	101
PLCB3	-0.001	0.009	-9999	-10000	0	0
FOS	-0.27	0.39	-9999	-0.84	272	272
positive regulation of mitosis	0.014	0.12	-9999	-0.57	19	19
LPA/LPA1-2-3	-0.075	0.18	-9999	-0.53	109	109
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
stress fiber formation	0.002	0.1	-9999	-0.42	13	13
GNAZ	0.012	0.09	-9999	-0.48	26	26
EGFR/PI3K-beta/Gab1	-0.2	0.27	-9999	-0.52	292	292
positive regulation of dendritic cell cytokine production	-0.075	0.18	-9999	-0.52	109	109
LPA/LPA2/MAGI-3	-0.002	0.022	-9999	-0.56	1	1
ARHGEF1	-0.009	0.06	-9999	-0.46	12	12
GNAI2	0.016	0.076	-9999	-0.45	20	20
GNAI3	0.016	0.076	-9999	-0.45	20	20
GNAI1	-0.013	0.16	-9999	-0.59	56	56
LPA/LPA3	-0.087	0.21	-9999	-0.65	101	101
LPA/LPA2	-0.001	0.014	-9999	-10000	0	0
LPA/LPA1	-0.013	0.084	-9999	-0.53	20	20
HB-EGF/EGFR	-0.25	0.27	-9999	-0.61	292	292
HBEGF	-0.063	0.1	-9999	-0.65	3	3
mol:DAG	-0.01	0.14	-9999	-0.38	101	101
cAMP biosynthetic process	-0.009	0.14	-9999	-0.56	38	38
NFKB1	0	0	-9999	-10000	0	0
SRC	0	0.01	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
LYN	-0.005	0.16	-9999	-0.42	101	101
GNAQ	-0.057	0.14	-9999	-0.43	103	103
LPAR2	0	0.01	-9999	-0.28	1	1
LPAR3	-0.11	0.27	-9999	-0.84	101	101
LPAR1	-0.014	0.1	-9999	-0.83	12	12
IL8	-0.19	0.23	-9999	-0.45	312	312
PTK2	-0.069	0.17	-9999	-0.49	109	109
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.064	0.16	-9999	-0.45	109	109
EGFR	-0.29	0.4	-9999	-0.83	297	297
PLCG1	-0.058	0.15	-9999	-0.45	102	102
PLD2	-0.069	0.17	-9999	-0.49	109	109
G12/G13	-0.01	0.065	-9999	-0.5	12	12
PI3K-beta	-0.01	0.063	-9999	-0.42	17	17
cell migration	-0.022	0.056	-9999	-0.26	5	5
SLC9A3R2	0	0	-9999	-10000	0	0
PXN	0.002	0.1	-9999	-0.43	13	13
HRAS/GTP	-0.031	0.11	-9999	-0.59	19	19
RAC1	0	0	-9999	-10000	0	0
MMP9	-0.12	0.14	-9999	-0.28	352	352
PRKCE	-0.001	0.029	-9999	-0.84	1	1
PRKCD	-0.001	0.13	-9999	-0.36	101	101
Gi(beta/gamma)	-0.031	0.11	-9999	-0.6	21	21
mol:LPA	-0.002	0.021	-9999	-0.22	8	8
TRIP6/p130 Cas/FAK1/Paxillin	-0.057	0.14	-9999	-0.5	23	23
MAPKKK cascade	0.014	0.12	-9999	-0.57	19	19
contractile ring contraction involved in cytokinesis	0.029	0.025	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.061	0.15	-9999	-0.45	105	105
GNA15	-0.057	0.14	-9999	-0.43	102	102
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
MAPT	-0.02	0.16	-9999	-0.45	88	88
GNA11	-0.056	0.14	-9999	-0.43	101	101
Rac1/GTP	-0.001	0.035	-9999	-1	1	1
MMP2	0.01	0.11	-9999	-0.69	20	20

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.017	0.03	-9999	-10000	0	0
VDR	0	0	-9999	-10000	0	0
FAM120B	0	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.037	0.16	-9999	-0.42	14	14
RXRs/LXRs/DNA/Oxysterols	-0.015	0.14	-9999	-0.47	13	13
MED1	-0.008	0.045	-9999	-10000	0	0
mol:9cRA	0.005	0.007	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.019	0.087	-9999	-0.38	42	42
RXRs/NUR77	-0.17	0.26	-9999	-0.55	258	258
RXRs/PPAR	-0.16	0.21	-9999	-0.52	114	114
NCOR2	0	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0	0	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	-0.006	0.048	-9999	-0.48	8	8
RARA	-0.004	0.033	-9999	-10000	0	0
NCOA1	-0.001	0.029	-9999	-0.84	1	1
VDR/VDR/DNA	0	0	-9999	-10000	0	0
RARs/RARs/DNA/9cRA	-0.006	0.049	-9999	-0.49	8	8
RARG	0	0	-9999	-10000	0	0
RPS6KB1	0.03	0.053	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.018	0.081	-9999	-0.36	42	42
THRA	-0.001	0.029	-9999	-0.84	1	1
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0	0	-9999	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.22	-9999	-0.5	204	204
NR1H4	-0.002	0.025	-9999	-0.28	7	7
RXRs/LXRs/DNA	-0.11	0.2	-9999	-0.46	204	204
NR1H2	0.016	0.005	-9999	-10000	0	0
NR1H3	0.016	0.006	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.12	0.2	-9999	-0.48	204	204
NR4A1	-0.079	0.24	-9999	-0.84	79	79
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.049	0.13	-9999	-0.28	204	204
RXRG	-0.19	0.36	-9999	-0.83	204	204
RXR alpha/CCPG	0	0	-9999	-10000	0	0
RXRA	0.016	0.005	-9999	-10000	0	0
RXRB	0.015	0.006	-9999	-10000	0	0
THRB	-0.036	0.17	-9999	-0.84	36	36
PPARG	-0.2	0.36	-9999	-0.84	197	197
PPARD	0	0	-9999	-10000	0	0
TNF	-0.015	0.19	-9999	-1.3	10	10
mol:Oxysterols	0.005	0.007	-9999	-10000	0	0
cholesterol transport	-0.015	0.14	-9999	-0.47	13	13
PPARA	-0.003	0.05	-9999	-0.84	3	3
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.008	0.081	-9999	-0.84	8	8
RXRs/NUR77/BCL2	-0.13	0.2	-9999	-0.4	270	270
SREBF1	-0.005	0.14	-9999	-0.68	3	3
RXRs/RXRs/DNA/9cRA	-0.12	0.22	-9999	-0.5	204	204
ABCA1	-0.007	0.15	-9999	-0.94	6	6
RARs/THRs	-0.027	0.12	-9999	-0.51	42	42
RXRs/FXR	-0.12	0.22	-9999	-0.51	204	204
BCL2	-0.024	0.14	-9999	-0.84	24	24

×

Signaling events mediated by the Hedgehog family

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.046	0.29	-10000	0	-0.84	91	91
IHH	-0.011	0.076	-10000	0	-0.5	2	2
SHH Np/Cholesterol/GAS1	-0.031	0.12	-10000	0	-0.53	46	46
LRPAP1	0	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.031	0.12	0.53	46	-10000	0	46
SMO/beta Arrestin2	-0.07	0.23	-10000	0	-0.87	57	57
SMO	-0.046	0.25	-10000	0	-0.93	57	57
AKT1	0	0.093	-10000	0	-0.34	11	11
ARRB2	0	0	-10000	0	-10000	0	0
BOC	-0.06	0.22	-10000	0	-0.84	60	60
ADRBK1	0	0.01	-10000	0	-0.28	1	1
heart looping	-0.028	0.25	-10000	0	-0.9	57	57
STIL	-0.035	0.21	-10000	0	-0.72	59	59
DHH N/PTCH2	-0.073	0.21	-10000	0	-0.68	91	91
DHH N/PTCH1	-0.084	0.24	-10000	0	-0.78	80	80
PIK3CA	0	0.01	-10000	0	-10000	0	0
DHH	-0.023	0.14	-10000	0	-0.81	24	24
PTHLH	-0.07	0.37	-10000	0	-1.1	91	91
determination of left/right symmetry	-0.028	0.25	-10000	0	-0.9	57	57
PIK3R1	0	0	-10000	0	-10000	0	0
skeletal system development	-0.067	0.36	-10000	0	-1.1	91	91
IHH N/Hhip	-0.009	0.048	-10000	0	-0.7	1	1
DHH N/Hhip	-0.021	0.11	-10000	0	-0.66	24	24
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.028	0.25	-10000	0	-0.9	57	57
pancreas development	-0.004	0.042	-10000	0	-0.84	1	1
HHAT	-0.001	0.029	-10000	0	-0.84	1	1
PI3K	0	0.006	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.045	0.19	-10000	0	-0.84	45	45
somite specification	-0.028	0.25	-10000	0	-0.9	57	57
SHH Np/Cholesterol/PTCH1	-0.066	0.2	-10000	0	-0.78	56	56
SHH Np/Cholesterol/PTCH2	-0.049	0.15	-10000	0	-0.53	74	74
SHH Np/Cholesterol/Megalin	-0.14	0.23	-10000	0	-0.52	219	219
SHH	0.01	0.037	-10000	0	-0.65	1	1
catabolic process	-0.041	0.25	-10000	0	-0.88	62	62
SMO/Vitamin D3	-0.069	0.22	-10000	0	-0.84	57	57
SHH Np/Cholesterol/Hhip	-0.006	0.038	-10000	0	-0.53	2	2
LRP2	-0.22	0.36	-10000	0	-0.79	239	239
receptor-mediated endocytosis	-0.15	0.25	-10000	0	-0.86	67	67
SHH Np/Cholesterol/BOC	-0.041	0.14	-10000	0	-0.53	61	61
SHH Np/Cholesterol/CDO	-0.01	0.062	-10000	0	-0.52	11	11
mesenchymal cell differentiation	0.006	0.037	0.52	2	-10000	0	2
mol:Vitamin D3	-0.025	0.22	-10000	0	-0.79	56	56
IHH N/PTCH2	-0.067	0.2	-10000	0	-0.72	73	73
CDON	-0.01	0.091	-10000	0	-0.84	10	10
IHH N/PTCH1	-0.038	0.26	-10000	0	-0.89	62	62
Megalin/LRPAP1	-0.17	0.28	-10000	0	-0.64	218	218
PTCH2	-0.073	0.24	-10000	0	-0.84	73	73
SHH Np/Cholesterol	-0.004	0.026	-10000	0	-0.53	1	1
PTCH1	-0.041	0.26	-10000	0	-0.89	62	62
HHIP	-0.004	0.042	-10000	0	-0.84	1	1

×

PDGFR-alpha signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.056	0.2	-9999	-0.85	49	49
PDGF/PDGFRA/CRKL	-0.037	0.15	-9999	-0.65	48	48
positive regulation of JUN kinase activity	-0.029	0.12	-9999	-0.5	48	48
CRKL	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.041	0.15	-9999	-0.66	48	48
AP1	-0.4	0.56	-9999	-1.2	272	272
mol:IP3	-0.034	0.16	-9999	-0.67	48	48
PLCG1	-0.034	0.16	-9999	-0.68	48	48
PDGF/PDGFRA/alphaV Integrin	-0.037	0.15	-9999	-0.65	48	48
RAPGEF1	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
mol:Ca2+	-0.034	0.16	-9999	-0.67	48	48
CAV3	-0.001	0.017	-9999	-0.28	3	3
CAV1	-0.17	0.34	-9999	-0.84	174	174
SHC/Grb2/SOS1	-0.029	0.12	-9999	-0.5	48	48
PDGF/PDGFRA/Shf	-0.038	0.15	-9999	-0.66	48	48
FOS	-0.36	0.57	-9999	-1.2	272	272
JUN	-0.028	0.077	-9999	-0.72	9	9
oligodendrocyte development	-0.037	0.15	-9999	-0.65	48	48
GRB2	0	0.01	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
mol:DAG	-0.034	0.16	-9999	-0.67	48	48
PDGF/PDGFRA	-0.056	0.2	-9999	-0.85	49	49
actin cytoskeleton reorganization	-0.038	0.15	-9999	-0.65	49	49
SRF	0.016	0.022	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
PI3K	-0.032	0.13	-9999	-0.56	48	48
PDGF/PDGFRA/Crk/C3G	-0.032	0.13	-9999	-0.56	48	48
JAK1	-0.022	0.16	-9999	-0.65	48	48
ELK1/SRF	-0.025	0.12	-9999	-0.51	48	48
SHB	-0.001	0.03	-9999	-0.84	1	1
SHF	-0.001	0.03	-9999	-0.56	2	2
CSNK2A1	0.02	0.027	-9999	-10000	0	0
GO:0007205	-0.035	0.16	-9999	-0.69	48	48
SOS1	0	0	-9999	-10000	0	0
Ras protein signal transduction	-0.029	0.12	-9999	-0.5	48	48
PDGF/PDGFRA/SHB	-0.038	0.15	-9999	-0.65	49	49
PDGF/PDGFRA/Caveolin-1	-0.17	0.33	-9999	-0.75	190	190
ITGAV	0	0	-9999	-10000	0	0
ELK1	-0.035	0.15	-9999	-0.62	48	48
PIK3CA	0	0.01	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.037	0.15	-9999	-0.65	48	48
JAK-STAT cascade	-0.022	0.15	-9999	-0.64	48	48
cell proliferation	-0.038	0.15	-9999	-0.66	48	48

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.008	0.061	-9999	-0.49	13	13
RGS9BP	-0.017	0.066	-9999	-0.28	51	51
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.003	0.027	-9999	-0.28	8	8
mol:Na +	-0.021	0.052	-9999	-10000	0	0
mol:ADP	0.007	0.026	-9999	-10000	0	0
GNAT2	-0.001	0.017	-9999	-0.28	3	3
RGS9-1/Gbeta5/R9AP	-0.071	0.18	-9999	-0.57	92	92
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.013	-9999	-10000	0	0
GRK7	-0.002	0.025	-9999	-10000	0	0
CNGB3	-0.011	0.053	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	-0.001	0.016	-9999	-0.19	6	6
mol:Ca2+	-0.099	0.076	-9999	-10000	0	0
Cone PDE6	-0.061	0.16	-9999	-0.49	92	92
Cone Metarhodopsin II	-0.002	0.018	-9999	-10000	0	0
Na + (4 Units)	-0.099	0.076	-9999	-10000	0	0
GNAT2/GDP	-0.061	0.15	-9999	-0.49	92	92
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	0.005	0.013	-9999	-10000	0	0
Cone Transducin	-0.009	0.064	-9999	-0.52	13	13
SLC24A2	-0.18	0.13	-9999	-0.28	546	546
GNB3/GNGT2	-0.01	0.08	-9999	-0.64	13	13
GNB3	-0.013	0.1	-9999	-0.76	14	14
GNAT2/GTP	-0.001	0.011	-9999	-0.19	3	3
CNGA3	-0.029	0.085	-9999	-0.28	88	88
ARR3	-0.002	0.023	-9999	-0.28	6	6
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.021	0.052	-9999	-10000	0	0
mol:Pi	-0.071	0.18	-9999	-0.57	92	92
Cone CNG Channel	-0.016	0.039	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.18	0.13	-9999	-0.28	546	546
RGS9	-0.095	0.26	-9999	-0.84	92	92
PDE6C	0	0	-9999	-10000	0	0
GNGT2	-0.001	0.029	-9999	-0.84	1	1
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.001	0.019	-9999	-0.28	4	4

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.6	0.38	-9999	-0.84	601	601
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	-0.001	0.019	-9999	-0.28	4	4
TCEB1	-0.001	0.017	-9999	-0.28	3	3
HIF1A/p53	-0.001	0.005	-9999	-10000	0	0
HIF1A	-0.002	0.007	-9999	-10000	0	0
COPS5	0	0.01	-9999	-0.28	1	1
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.001	0.009	-9999	-10000	0	0
FIH (dimer)	0	0	-9999	-10000	0	0
CDKN2A	-0.044	0.1	-9999	-0.28	133	133
ARNT/IPAS	-0.46	0.29	-9999	-0.64	601	601
HIF1AN	0	0	-9999	-10000	0	0
GNB2L1	0	0	-9999	-10000	0	0
HIF1A/ARNT	-0.001	0.005	-9999	-10000	0	0
CUL2	0	0	-9999	-10000	0	0
OS9	0	0.01	-9999	-0.28	1	1
RACK1/Elongin B/Elongin C	-0.001	0.012	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.001	0.006	-9999	-10000	0	0
PHD1-3/OS9	-0.01	0.035	-9999	-0.51	1	1
HIF1A/RACK1/Elongin B/Elongin C	0	0.008	-9999	-10000	0	0
VHL	0	0	-9999	-10000	0	0
HSP90AA1	0	0.01	-9999	-0.28	1	1
HIF1A/JAB1	-0.001	0.006	-9999	-10000	0	0
EGLN3	-0.023	0.076	-9999	-0.28	69	69
EGLN2	-0.001	0.017	-9999	-0.28	3	3
EGLN1	-0.001	0.029	-9999	-0.84	1	1
TP53	0	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0	0.004	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.016	0.036	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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
ERK1-2/ELK1	-0.13	0.19	-9999	-0.39	274	274
MAP3K8	-0.005	0.066	-9999	-0.75	6	6
FOS	-0.041	0.14	-9999	-0.46	27	27
PRKCA	-0.022	0.13	-9999	-0.78	24	24
PTPN7	-0.007	0.068	-9999	-10000	0	0
HRAS	0	0.01	-9999	-10000	0	0
PRKCB	-0.018	0.11	-9999	-0.57	27	27
NRAS	-0.001	0.014	-9999	-10000	0	0
RAS family/GTP	-0.001	0.009	-9999	-10000	0	0
MAPK3	-0.011	0.073	-9999	-10000	0	0
MAP2K1	-0.015	0.14	-9999	-0.6	37	37
ELK1	-0.003	0.005	-9999	-10000	0	0
BRAF	-0.033	0.12	-9999	-0.61	33	33
mol:GTP	-0.002	0.003	-9999	-0.006	272	272
MAPK1	-0.011	0.073	-9999	-10000	0	0
RAF1	-0.033	0.12	-9999	-0.61	33	33
KRAS	0	0.01	-9999	-10000	0	0

×

Syndecan-3-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.003	0.027	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.2	0.22	-9999	-0.44	373	373
Syndecan-3/Neurocan	-0.007	0.025	-9999	-10000	0	0
POMC	-0.022	0.12	-9999	-0.52	35	35
EGFR	-0.29	0.4	-9999	-0.83	297	297
Syndecan-3/EGFR	-0.17	0.23	-9999	-0.48	292	292
AGRP	-0.002	0.025	-9999	-10000	0	0
NCSTN	0	0	-9999	-10000	0	0
PSENEN	0	0.01	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	-0.001	0.029	-9999	-0.84	1	1
APH1A	0	0	-9999	-10000	0	0
NCAN	-0.017	0.067	-9999	-10000	0	0
long-term memory	-0.001	0.018	-9999	-0.44	1	1
Syndecan-3/IL8	-0.017	0.071	-9999	-0.48	17	17
PSEN1	0	0	-9999	-10000	0	0
Src/Cortactin	-0.002	0.018	-9999	-10000	0	0
FYN	-0.001	0.029	-9999	-0.84	1	1
limb bud formation	0	0.003	-9999	-10000	0	0
MC4R	-0.004	0.033	-9999	-0.28	12	12
SRC	0	0.01	-9999	-10000	0	0
PTN	-0.37	0.42	-9999	-0.84	373	373
FGFR/FGF/Syndecan-3	0	0.003	-9999	-10000	0	0
neuron projection morphogenesis	-0.19	0.21	-9999	-0.52	33	33
Syndecan-3/AgRP	-0.001	0.01	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	-0.002	0.014	-9999	-10000	0	0
Fyn/Cortactin	-0.002	0.028	-9999	-0.64	1	1
SDC3	0	0.003	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.017	0.07	-9999	-0.47	17	17
IL8	-0.036	0.14	-9999	-0.84	17	17
Syndecan-3/Fyn/Cortactin	-0.001	0.018	-9999	-0.46	1	1
Syndecan-3/CASK	0	0.003	-9999	-10000	0	0
alpha-MSH/MC4R	-0.018	0.093	-9999	-0.62	17	17
Gamma Secretase	-0.001	0.017	-9999	-0.48	1	1

×

Presenilin action in Notch and Wnt signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.002	0.032	-10000	0	-0.47	4	4
HDAC1	0.002	0.008	-10000	0	-10000	0	0
AES	0.001	0.003	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
DTX1	-0.077	0.24	-10000	0	-0.84	77	77
LRP6/FZD1	0	0.009	-10000	0	-10000	0	0
TLE1	-0.006	0.071	-10000	0	-0.84	6	6
AP1	-0.13	0.19	-10000	0	-0.39	276	276
NCSTN	0	0	-10000	0	-10000	0	0
ADAM10	0	0.001	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.008	0.046	-10000	0	-0.34	1	1
NICD/RBPSUH	0	0.003	-10000	0	-10000	0	0
WIF1	-0.44	0.42	-10000	0	-0.84	440	440
NOTCH1	0	0.003	-10000	0	-10000	0	0
PSENEN	0	0.01	-10000	0	-10000	0	0
KREMEN2	-0.13	0.14	-10000	0	-0.28	389	389
DKK1	-0.08	0.2	-10000	0	-0.84	43	43
beta catenin/beta TrCP1	-0.011	0.024	0.23	2	-10000	0	2
APH1B	-0.001	0.029	-10000	0	-0.84	1	1
APH1A	0	0	-10000	0	-10000	0	0
AXIN1	0.003	0.009	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.003	0.04	-10000	0	-0.35	6	6
PSEN1	0	0	-10000	0	-10000	0	0
FOS	-0.27	0.39	-10000	0	-0.84	272	272
JUN	-0.009	0.086	-10000	0	-0.84	9	9
MAP3K7	0	0.011	-10000	0	-0.28	1	1
CTNNB1	-0.004	0.037	0.23	4	-10000	0	4
MAPK3	0	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.074	0.11	-10000	0	-0.66	17	17
HNF1A	-0.002	0.026	-10000	0	-0.28	7	7
CTBP1	0.001	0.003	-10000	0	-10000	0	0
MYC	-0.036	0.23	-10000	0	-1.5	20	20
NKD1	-0.011	0.08	-10000	0	-0.43	22	22
FZD1	0	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.043	0.14	-10000	0	-0.47	77	77
apoptosis	-0.13	0.19	-10000	0	-0.39	276	276
Delta 1/NOTCHprecursor	-0.002	0.032	-10000	0	-0.47	4	4
DLL1	-0.004	0.058	-10000	0	-0.84	4	4
PPARD	-0.001	0.013	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.017	-10000	0	-0.48	1	1
APC	0.003	0.009	-10000	0	-10000	0	0
DVL1	-0.04	0.038	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.11	0.15	-10000	0	-0.6	45	45
LRP6	-0.001	0.014	-10000	0	-10000	0	0
CSNK1A1	0	0	-10000	0	-10000	0	0
NLK	0.002	0.011	-10000	0	-10000	0	0
CCND1	-0.011	0.094	-10000	0	-1.5	3	3
WNT1	0	0.01	-10000	0	-0.28	1	1
Axin1/APC/beta catenin	0.009	0.037	-10000	0	-10000	0	0
DKK2	-0.018	0.12	-10000	0	-0.78	19	19
NOTCH1 precursor/DVL1	-0.019	0.019	-10000	0	-10000	0	0
GSK3B	0	0.002	-10000	0	-10000	0	0
FRAT1	0	0.003	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.043	0.14	-10000	0	-0.47	77	77
PPP2R5D	-0.016	0.042	0.36	6	-10000	0	6
MAPK1	0	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.27	0.25	-10000	0	-0.51	440	440
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.013	0.004	-10000	0	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	-0.001	0.029	-9999	-0.84	1	1
LAT2	-0.064	0.14	-9999	-0.44	66	66
AP1	-0.17	0.23	-9999	-0.6	118	118
mol:PIP3	-0.031	0.21	-9999	-0.52	68	68
IKBKB	0	0.12	-9999	-0.33	35	35
AKT1	-0.084	0.18	-9999	-0.7	28	28
IKBKG	0.001	0.12	-9999	-0.33	35	35
MS4A2	-0.066	0.22	-9999	-0.84	65	65
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0	0.01	-9999	-10000	0	0
MAP3K1	0.006	0.13	-9999	-0.45	27	27
mol:Ca2+	-0.015	0.16	-9999	-0.38	68	68
LYN	0.011	0.004	-9999	-10000	0	0
CBLB	-0.063	0.14	-9999	-0.44	66	66
SHC1	0	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.072	0.18	-9999	-0.52	117	117
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0	0	-9999	-10000	0	0
PLD2	-0.1	0.22	-9999	-0.51	170	170
PTPN13	-0.032	0.17	-9999	-0.56	45	45
PTPN11	0.01	0.006	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.006	0.15	-9999	-0.42	27	27
SYK	0.01	0.011	-9999	-10000	0	0
GRB2	0	0.01	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.09	0.19	-9999	-0.54	68	68
LAT	-0.065	0.14	-9999	-0.59	29	29
PAK2	-0.003	0.14	-9999	-0.5	28	28
NFATC2	-0.079	0.21	-9999	-0.89	47	47
HRAS	-0.013	0.15	-9999	-0.56	28	28
GAB2	-0.003	0.027	-9999	-0.28	8	8
PLA2G1B	0.028	0.019	-9999	-10000	0	0
Fc epsilon R1	-0.13	0.27	-9999	-0.63	170	170
Antigen/IgE/Fc epsilon R1	-0.12	0.25	-9999	-0.59	170	170
mol:GDP	-0.019	0.15	-9999	-0.57	28	28
JUN	-0.009	0.086	-9999	-0.84	9	9
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
FOS	-0.27	0.39	-9999	-0.84	272	272
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.068	0.15	-9999	-0.46	66	66
CHUK	0.001	0.12	-9999	-0.33	35	35
KLRG1	-0.063	0.14	-9999	-0.57	28	28
VAV1	-0.064	0.14	-9999	-0.59	29	29
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.063	0.14	-9999	-0.58	28	28
negative regulation of mast cell degranulation	-0.057	0.12	-9999	-0.52	28	28
BTK	-0.061	0.14	-9999	-0.57	28	28
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.089	0.2	-9999	-0.47	138	138
GAB2/PI3K/SHP2	-0.093	0.2	-9999	-0.76	30	30
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.072	0.16	-9999	-0.73	28	28
RAF1	0.015	0.022	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.11	0.23	-9999	-0.54	171	171
FCER1G	0.003	0.013	-9999	-0.28	1	1
FCER1A	-0.12	0.31	-9999	-0.85	131	131
Antigen/IgE/Fc epsilon R1/Fyn	-0.11	0.23	-9999	-0.55	170	170
MAPK3	0.026	0.019	-9999	-10000	0	0
MAPK1	0.026	0.019	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0.013	0.05	-9999	-0.61	1	1
DUSP1	-0.12	0.29	-9999	-0.84	117	117
NF-kappa-B/RelA	-0.028	0.055	-9999	-0.24	1	1
actin cytoskeleton reorganization	-0.028	0.15	-9999	-0.56	27	27
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.054	0.12	-9999	-0.53	27	27
FER	-0.066	0.14	-9999	-0.59	32	32
RELA	0	0	-9999	-10000	0	0
ITK	-0.033	0.11	-9999	-0.62	25	25
SOS1	0	0	-9999	-10000	0	0
PLCG1	-0.017	0.16	-9999	-0.59	28	28
cytokine secretion	-0.02	0.04	-9999	-10000	0	0
SPHK1	-0.065	0.14	-9999	-0.59	30	30
PTK2	-0.03	0.16	-9999	-0.59	27	27
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.094	0.2	-9999	-0.55	74	74
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.026	0.2	-9999	-0.5	68	68
MAP2K2	0.023	0.019	-9999	-10000	0	0
MAP2K1	0.023	0.019	-9999	-10000	0	0
MAP2K7	0	0	-9999	-10000	0	0
KLRG1/SHP2	-0.059	0.13	-9999	-0.53	28	28
MAP2K4	0.015	0.038	-9999	-1	1	1
Fc epsilon R1/FcgammaRIIB	-0.12	0.25	-9999	-0.58	171	171
mol:Choline	-0.1	0.21	-9999	-0.5	170	170
SHC/Grb2/SOS1	-0.057	0.13	-9999	-0.55	27	27
FYN	-0.001	0.029	-9999	-0.84	1	1
DOK1	0	0	-9999	-10000	0	0
PXN	-0.02	0.15	-9999	-0.55	26	26
HCLS1	-0.063	0.14	-9999	-0.58	28	28
PRKCB	-0.017	0.16	-9999	-0.39	72	72
FCGR2B	-0.003	0.051	-9999	-0.84	3	3
IGHE	0	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.058	0.13	-9999	-0.53	28	28
LCP2	0	0.01	-9999	-0.28	1	1
PLA2G4A	-0.11	0.21	-9999	-0.53	142	142
RASA1	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.1	0.21	-9999	-0.5	170	170
IKK complex	0.018	0.095	-9999	-0.23	34	34
WIPF1	0	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class III

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0	0	-10000	0	-10000	0	0
HDAC4	-0.001	0.029	-10000	0	-0.84	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.03	0.07	0.64	1	-10000	0	1
CDKN1A	-0.001	0.034	-10000	0	-0.98	1	1
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0	0	-10000	0	-10000	0	0
FOXO3	-0.001	0.017	-10000	0	-0.34	2	2
FOXO1	-0.006	0.07	-10000	0	-0.84	6	6
FOXO4	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
TAT	-0.61	0.37	-10000	0	-0.82	626	626
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.011	0.02	-10000	0	-10000	0	0
PPARGC1A	-0.19	0.35	-10000	0	-0.81	196	196
FHL2	-0.006	0.066	-10000	0	-0.68	7	7
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.005	-10000	0	-10000	0	0
HIST2H4A	-0.03	0.07	-10000	0	-0.65	1	1
SIRT1/FOXO3a	0	0.014	-10000	0	-0.26	2	2
SIRT1	0	0.007	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0.02	-10000	0	-0.56	1	1
SIRT1/Histone H1b	-0.002	0.009	-10000	0	-10000	0	0
apoptosis	0	0.005	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.13	0.24	-10000	0	-0.57	186	186
p53/SIRT1	0.001	0.016	0.43	1	-10000	0	1
SIRT1/FOXO4	0	0.006	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.007	0.059	-10000	0	-0.52	11	11
HIST1H1E	-0.004	0.012	-10000	0	-10000	0	0
SIRT1/p300	0	0.005	-10000	0	-10000	0	0
muscle cell differentiation	0.001	0.015	-10000	0	-10000	0	0
TP53	0	0.007	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.005	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0
MEF2D	0	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.47	0.28	-10000	0	-0.65	602	602
ACSS2	0	0.005	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.001	0.015	-10000	0	-10000	0	0

×

TCGA08_rtk_signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.048	0.19	-10000	0	-0.83	49	49
HRAS	0	0.01	-10000	0	-10000	0	0
EGFR	-0.29	0.4	-10000	0	-0.83	297	297
AKT	0.016	0.073	-10000	0	-0.58	11	11
FOXO3	-0.002	0.041	-10000	0	-0.84	2	2
AKT1	0	0	-10000	0	-10000	0	0
FOXO1	-0.006	0.07	-10000	0	-0.84	6	6
AKT3	-0.011	0.095	-10000	0	-0.84	11	11
FOXO4	0	0	-10000	0	-10000	0	0
MET	-0.14	0.32	-10000	0	-0.83	144	144
PIK3CA	0	0.01	-10000	0	-10000	0	0
PIK3CB	0	0	-10000	0	-10000	0	0
NRAS	-0.001	0.014	-10000	0	-10000	0	0
PIK3CG	-0.008	0.078	-10000	0	-0.84	7	7
PIK3R3	0	0.01	-10000	0	-0.28	1	1
PIK3R2	0	0	-10000	0	-10000	0	0
NF1	-0.001	0.029	-10000	0	-0.84	1	1
RAS	-0.091	0.16	0.26	1	-0.37	157	158
ERBB2	-0.025	0.079	-10000	0	-0.28	75	75
proliferation/survival/translation	-0.006	0.054	0.28	4	-10000	0	4
PI3K	-0.08	0.16	-10000	0	-0.27	303	303
PIK3R1	0	0	-10000	0	-10000	0	0
KRAS	0	0.01	-10000	0	-10000	0	0
FOXO	0.027	0.024	-10000	0	-10000	0	0
AKT2	0	0	-10000	0	-10000	0	0
PTEN	-0.002	0.041	-10000	0	-0.84	2	2

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.01	0.058	-10000	0	-0.34	25	25
epithelial cell differentiation	-0.014	0.08	-10000	0	-0.48	24	24
CYFIP2	-0.009	0.06	-10000	0	-0.32	24	24
ENAH	0.056	0.064	-10000	0	-10000	0	0
EGFR	-0.29	0.4	-10000	0	-0.83	297	297
EPHA2	-0.006	0.07	-10000	0	-0.84	6	6
MYO6	-0.014	0.077	-10000	0	-0.45	25	25
CTNNB1	0	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.005	0.034	-10000	0	-0.56	2	2
AQP5	-0.26	0.31	-10000	0	-0.62	346	346
CTNND1	0	0.01	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.013	0.074	-10000	0	-0.44	24	24
regulation of calcium-dependent cell-cell adhesion	-0.037	0.13	-10000	0	-0.46	68	68
EGF	-0.17	0.33	-10000	0	-0.84	167	167
NCKAP1	0	0	-10000	0	-10000	0	0
AQP3	-0.041	0.15	-10000	0	-0.61	44	44
cortical microtubule organization	-0.014	0.08	-10000	0	-0.48	24	24
GO:0000145	0.024	0.077	-10000	0	-0.42	24	24
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.014	0.081	-10000	0	-0.48	24	24
MLLT4	-0.003	0.05	-10000	0	-0.84	3	3
ARF6/GDP	-0.014	0.069	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.004	0.044	-10000	0	-0.51	6	6
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.036	0.079	-10000	0	-0.42	24	24
PVRL2	-0.001	0.017	-10000	0	-0.28	3	3
ZYX	-0.013	0.075	-10000	0	-0.45	24	24
ARF6/GTP	-0.004	0.04	-10000	0	-0.47	6	6
CDH1	-0.024	0.14	-10000	0	-0.84	24	24
EGFR/EGFR/EGF/EGF	-0.25	0.28	-10000	0	-0.5	423	423
RhoA/GDP	-0.013	0.075	-10000	0	-0.45	24	24
actin cytoskeleton organization	0.031	0.08	-10000	0	-0.42	25	25
IGF-1R heterotetramer	-0.02	0.12	-10000	0	-0.84	16	16
GIT1	-0.001	0.019	-10000	0	-10000	0	0
IGF1R	-0.02	0.12	-10000	0	-0.84	16	16
IGF1	-0.18	0.35	-10000	0	-0.84	186	186
DIAPH1	-0.001	0.035	-10000	0	-0.68	2	2
Wnt receptor signaling pathway	0.014	0.08	0.48	24	-10000	0	24
RHOA	0	0	-10000	0	-10000	0	0
RhoA/GTP	-0.014	0.07	-10000	0	-10000	0	0
CTNNA1	0	0	-10000	0	-10000	0	0
VCL	-0.013	0.074	-10000	0	-0.44	25	25
EFNA1	0	0.01	-10000	0	-10000	0	0
LPP	0.031	0.082	-10000	0	-0.42	26	26
Ephrin A1/EPHA2	-0.016	0.08	-10000	0	-0.43	30	30
SEC6/SEC8	-0.013	0.07	-10000	0	-10000	0	0
MGAT3	-0.038	0.13	-10000	0	-0.47	68	68
HGF/MET	-0.11	0.22	-10000	0	-0.49	195	195
HGF	-0.05	0.2	-10000	0	-0.84	50	50
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.01	0.058	-10000	0	-0.34	25	25
actin cable formation	0.071	0.06	-10000	0	-10000	0	0
KIAA1543	0.031	0.089	-10000	0	-0.46	24	24
KIFC3	-0.014	0.079	-10000	0	-0.45	26	26
NCK1	0	0	-10000	0	-10000	0	0
EXOC3	0	0	-10000	0	-10000	0	0
ACTN1	-0.014	0.077	-10000	0	-0.45	25	25
NCK1/GIT1	-0.001	0.012	-10000	0	-10000	0	0
mol:GDP	-0.014	0.08	-10000	0	-0.48	24	24
EXOC4	0	0	-10000	0	-10000	0	0
STX4	-0.013	0.075	-10000	0	-0.45	24	24
PIP5K1C	-0.013	0.075	-10000	0	-0.45	24	24
LIMA1	-0.001	0.029	-10000	0	-0.84	1	1
ABI1	0	0	-10000	0	-10000	0	0
ROCK1	-0.012	0.06	-10000	0	-10000	0	0
adherens junction assembly	0.047	0.085	-10000	0	-0.63	3	3
IGF-1R heterotetramer/IGF1	-0.12	0.21	-10000	0	-0.46	215	215
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.003	0.04	-10000	0	-0.64	3	3
MET	-0.14	0.32	-10000	0	-0.83	144	144
PLEKHA7	-0.014	0.08	-10000	0	-0.47	24	24
mol:GTP	-0.004	0.043	-10000	0	-0.5	6	6
establishment of epithelial cell apical/basal polarity	-0.012	0.066	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	-0.01	0.058	-10000	0	-0.34	25	25
regulation of cell-cell adhesion	0.031	0.08	-10000	0	-0.42	25	25
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.01	0.058	-10000	0	-0.34	25	25

×

E-cadherin signaling in keratinocytes

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.005	0.027	-9999	-10000	0	0
adherens junction organization	0.033	0.064	-9999	-0.31	25	25
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	-0.14	0.19	-9999	-0.57	11	11
FMN1	0.027	0.083	-9999	-0.48	11	11
mol:IP3	-0.005	0.029	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.01	0.056	-9999	-0.33	25	25
CTNNB1	0.001	0.004	-9999	-10000	0	0
AKT1	-0.006	0.033	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.015	0.087	-9999	-0.52	24	24
CTNND1	0	0.009	-9999	-10000	0	0
mol:PI-4-5-P2	0.033	0.058	-9999	-0.3	25	25
VASP	0.033	0.059	-9999	-0.3	25	25
ZYX	0.033	0.059	-9999	-10000	0	0
JUB	0.031	0.068	-9999	-0.32	29	29
EGFR(dimer)	-0.16	0.22	-9999	-0.46	293	293
E-cadherin/beta catenin-gamma catenin	-0.016	0.092	-9999	-0.54	25	25
mol:PI-3-4-5-P3	-0.006	0.036	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-10000	0	0
PI3K	-0.006	0.037	-9999	-10000	0	0
FYN	0.044	0.036	-9999	-0.4	1	1
mol:Ca2+	-0.005	0.028	-9999	-10000	0	0
JUP	-0.001	0.032	-9999	-0.46	3	3
PIK3R1	0	0	-9999	-10000	0	0
mol:DAG	-0.005	0.029	-9999	-10000	0	0
CDH1	-0.024	0.14	-9999	-0.84	24	24
RhoA/GDP	-0.14	0.19	-9999	-0.4	292	292
establishment of polarity of embryonic epithelium	0.033	0.058	-9999	-0.3	25	25
SRC	0	0.01	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
EGFR	-0.29	0.4	-9999	-0.83	297	297
CASR	-0.005	0.027	-9999	-10000	0	0
RhoA/GTP	-0.004	0.025	-9999	-10000	0	0
AKT2	-0.006	0.033	-9999	-10000	0	0
actin cable formation	0.034	0.081	-9999	-0.46	11	11
apoptosis	0.006	0.032	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
mol:GDP	-0.15	0.2	-9999	-0.43	292	292
PIP5K1A	0.033	0.059	-9999	-0.3	25	25
PLCG1	-0.005	0.029	-9999	-10000	0	0
Rac1/GTP	-0.15	0.2	-9999	-0.42	293	293
homophilic cell adhesion	0.001	0.001	-9999	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.075	0.18	0.68	61	-10000	0	61
KIRREL	-0.061	0.22	-10000	0	-0.84	61	61
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.075	0.18	-10000	0	-0.68	61	61
PLCG1	0	0	-10000	0	-10000	0	0
ARRB2	0	0	-10000	0	-10000	0	0
WASL	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.054	0.14	-10000	0	-0.52	61	61
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.03	0.098	-10000	0	-0.38	61	61
FYN	-0.05	0.13	-10000	0	-0.5	61	61
mol:Ca2+	-0.054	0.14	-10000	0	-0.52	61	61
mol:DAG	-0.054	0.14	-10000	0	-0.52	61	61
NPHS2	-0.008	0.03	-10000	0	-0.29	1	1
mol:IP3	-0.054	0.14	-10000	0	-0.52	61	61
regulation of endocytosis	-0.022	0.13	-10000	0	-0.46	61	61
Nephrin/NEPH1/podocin/Cholesterol	-0.056	0.14	-10000	0	-0.53	61	61
establishment of cell polarity	-0.075	0.18	-10000	0	-0.68	61	61
Nephrin/NEPH1/podocin/NCK1-2	-0.021	0.13	-10000	0	-0.48	61	61
Nephrin/NEPH1/beta Arrestin2	-0.022	0.13	-10000	0	-0.47	61	61
NPHS1	-0.049	0.1	-10000	0	-0.35	10	10
Nephrin/NEPH1/podocin	-0.044	0.13	-10000	0	-0.5	61	61
TJP1	-0.001	0.029	-10000	0	-0.84	1	1
NCK1	0	0	-10000	0	-10000	0	0
NCK2	0	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.054	0.14	-10000	0	-0.52	61	61
CD2AP	0	0.01	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.054	0.14	-10000	0	-0.52	61	61
GRB2	0	0.01	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.056	0.14	-10000	0	-0.52	67	67
cytoskeleton organization	-0.039	0.12	-10000	0	-0.48	61	61
Nephrin/NEPH1	-0.054	0.14	-10000	0	-0.51	61	61
Nephrin/NEPH1/ZO-1	-0.059	0.15	-10000	0	-0.57	61	61

×

Rapid glucocorticoid 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.11	0.21	-10000	0	-0.5	191	191
MAPK9	0	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.001	0.02	-10000	0	-10000	0	0
GNB1/GNG2	-0.004	0.048	-10000	0	-0.57	6	6
GNB1	0	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0	0	-10000	0	-10000	0	0
Gs family/GTP	-0.12	0.22	-10000	0	-0.53	190	190
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.027	0.049	0.12	190	-10000	0	190
GNAL	-0.19	0.35	-10000	0	-0.84	190	190
GNG2	-0.006	0.07	-10000	0	-0.84	6	6
CRH	-0.003	0.029	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0	0	-10000	0	-10000	0	0
MAPK11	-0.001	0.023	-10000	0	-0.46	2	2

×

LPA4-mediated signaling events

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
ADCY4	-0.002	0.11	-9999	-0.57	31	31
ADCY5	-0.17	0.28	-9999	-0.57	267	267
ADCY6	0.019	0.02	-9999	-0.57	1	1
ADCY7	0.019	0.02	-9999	-0.57	1	1
ADCY1	-0.007	0.097	-9999	-0.57	19	19
ADCY2	-0.034	0.16	-9999	-0.57	67	67
ADCY3	0.019	0.021	-9999	-0.57	1	1
ADCY8	0.009	0.033	-9999	-0.57	1	1
PRKCE	0.01	0.023	-9999	-0.66	1	1
ADCY9	0.019	0.02	-9999	-0.57	1	1
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.033	0.11	-9999	-0.33	55	55

×

FAS signaling pathway (CD95)

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
SPTAN1	0.009	0.049	0.29	24	-10000	0	24
RFC1	0.009	0.049	0.29	24	-10000	0	24
PRKDC	0.008	0.05	0.29	24	-10000	0	24
RIPK1	0	0	-10000	0	-10000	0	0
CASP7	-0.024	0.036	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.016	0.059	0.26	9	-0.4	7	16
MAP2K4	-0.063	0.16	-10000	0	-0.4	25	25
mol:ceramide	-0.058	0.093	-10000	0	-0.6	10	10
GSN	0	0.082	0.29	23	-0.53	13	36
FASLG/FAS/FADD/FAF1/Caspase 8	-0.03	0.063	0.23	9	-0.49	7	16
FAS	-0.002	0.041	-10000	0	-0.85	2	2
BID	0	0.005	-10000	0	-10000	0	0
MAP3K1	-0.024	0.093	-10000	0	-0.29	9	9
MAP3K7	0	0.01	-10000	0	-0.28	1	1
RB1	0.008	0.052	0.29	24	-0.55	1	25
CFLAR	0	0	-10000	0	-10000	0	0
HGF/MET	-0.14	0.28	-10000	0	-0.63	187	187
ARHGDIB	0.008	0.049	0.29	24	-10000	0	24
FADD	-0.006	0.041	-10000	0	-0.3	16	16
actin filament polymerization	0	0.082	0.53	13	-0.29	23	36
NFKB1	-0.08	0.1	-10000	0	-0.3	7	7
MAPK8	-0.12	0.24	-10000	0	-0.43	323	323
DFFA	0.009	0.049	0.29	24	-10000	0	24
DNA fragmentation during apoptosis	0.009	0.049	0.29	24	-10000	0	24
FAS/FADD/MET	-0.1	0.22	-10000	0	-0.59	143	143
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.001	0.047	-10000	0	-10000	0	0
FAF1	0	0	-10000	0	-10000	0	0
PARP1	0.009	0.049	0.29	24	-10000	0	24
DFFB	0.009	0.049	0.29	24	-10000	0	24
CHUK	-0.069	0.089	-10000	0	-10000	0	0
FASLG	-0.017	0.09	-10000	0	-0.37	39	39
FAS/FADD	-0.005	0.044	-10000	0	-0.73	2	2
HGF	-0.05	0.2	-10000	0	-0.84	50	50
LMNA	0.008	0.044	0.26	24	-10000	0	24
CASP6	0.009	0.049	0.29	24	-10000	0	24
CASP10	-0.003	0.051	-10000	0	-0.85	3	3
CASP3	0.01	0.059	0.36	24	-10000	0	24
PTPN13	-0.022	0.13	-10000	0	-0.84	22	22
CASP8	0.002	0.013	-10000	0	-10000	0	0
IL6	-0.5	0.69	-10000	0	-1.4	323	323
MET	-0.14	0.32	-10000	0	-0.83	144	144
ICAD/CAD	0.008	0.045	0.27	24	-10000	0	24
FASLG/FAS/FADD/FAF1/Caspase 10	-0.058	0.094	-10000	0	-0.61	10	10
activation of caspase activity by cytochrome c	0	0.005	-10000	0	-10000	0	0
PAK2	0.009	0.048	0.29	24	-10000	0	24
BCL2	-0.02	0.14	-10000	0	-0.84	24	24

×

S1P1 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
VEGFR2 homodimer/VEGFA homodimer	-0.003	0.037	-9999	-0.66	2	2
PDGFRB	-0.002	0.041	-9999	-0.84	2	2
SPHK1	-0.025	0.061	-9999	-1.1	2	2
mol:S1P	-0.031	0.062	-9999	-0.99	2	2
S1P1/S1P/Gi	-0.1	0.23	-9999	-0.61	67	67
GNAO1	-0.033	0.14	-9999	-0.85	21	21
PDGFB-D/PDGFRB/PLCgamma1	-0.12	0.18	-9999	-0.61	51	51
PLCG1	-0.089	0.22	-9999	-0.65	50	50
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.002	0.041	-9999	-0.84	2	2
GNAI2	0	0.001	-9999	-10000	0	0
GNAI3	0	0.001	-9999	-10000	0	0
GNAI1	-0.043	0.19	-9999	-0.85	43	43
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.007	0.035	-9999	-0.58	2	2
S1P1/S1P	-0.044	0.073	-9999	-0.69	4	4
negative regulation of cAMP metabolic process	-0.096	0.22	-9999	-0.59	67	67
MAPK3	-0.16	0.31	-9999	-0.57	281	281
calcium-dependent phospholipase C activity	-0.003	0.004	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	-0.002	0.041	-9999	-0.84	2	2
PLCB2	-0.007	0.085	-9999	-0.57	5	5
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.037	0.06	-9999	-0.55	4	4
receptor internalization	-0.042	0.068	-9999	-0.62	4	4
PTGS2	-0.33	0.56	-9999	-1.1	281	281
Rac1/GTP	-0.037	0.06	-9999	-0.55	4	4
RHOA	0	0	-9999	-10000	0	0
VEGFA	-0.003	0.029	-9999	-0.28	9	9
negative regulation of T cell proliferation	-0.096	0.22	-9999	-0.59	67	67
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.006	0.071	-9999	-0.84	6	6
MAPK1	-0.16	0.31	-9999	-0.57	281	281
S1P1/S1P/PDGFB-D/PDGFRB	-0.052	0.086	-9999	-0.72	5	5
ABCC1	0	0	-9999	-10000	0	0

×

Syndecan-4-mediated signaling events

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
PTK2	0	0.031	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.019	0.034	-9999	-0.66	1	1
positive regulation of JNK cascade	-0.048	0.11	-9999	-0.44	29	29
Syndecan-4/ADAM12	-0.03	0.055	-9999	-0.57	2	2
CCL5	-0.011	0.063	-9999	-0.84	2	2
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0	0	-9999	-10000	0	0
ITGA5	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
PLG	-0.001	0.023	-9999	-10000	0	0
ADAM12	-0.023	0.084	-9999	-0.3	67	67
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	-0.001	0.014	-9999	-0.28	2	2
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.056	0.044	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.071	0.14	-9999	-0.49	49	49
Syndecan-4/CXCL12/CXCR4	-0.05	0.12	-9999	-0.46	29	29
Syndecan-4/Laminin alpha3	-0.13	0.2	-9999	-0.51	150	150
MDK	-0.01	0.051	-9999	-10000	0	0
Syndecan-4/FZD7	-0.028	0.069	-9999	-0.5	10	10
Syndecan-4/Midkine	-0.021	0.04	-9999	-0.66	1	1
FZD7	-0.016	0.11	-9999	-0.84	16	16
Syndecan-4/FGFR1/FGF	-0.19	0.22	-9999	-0.52	83	83
THBS1	-0.001	0.029	-9999	-0.84	1	1
integrin-mediated signaling pathway	-0.029	0.072	-9999	-0.51	11	11
positive regulation of MAPKKK cascade	-0.048	0.11	-9999	-0.44	29	29
Syndecan-4/TACI	-0.03	0.068	-9999	-0.53	6	6
CXCR4	-0.009	0.048	-9999	-0.28	26	26
cell adhesion	-0.027	0.058	-9999	-0.36	21	21
Syndecan-4/Dynamin	-0.019	0.033	-9999	-0.66	1	1
Syndecan-4/TSP1	-0.02	0.036	-9999	-0.66	1	1
Syndecan-4/GIPC	-0.019	0.033	-9999	-0.66	1	1
Syndecan-4/RANTES	-0.024	0.045	-9999	-0.6	2	2
ITGB1	0	0	-9999	-10000	0	0
LAMA1	-0.095	0.26	-9999	-0.83	97	97
LAMA3	-0.2	0.36	-9999	-0.84	201	201
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.003	0.13	-9999	-0.75	23	23
Syndecan-4/alpha-Actinin	-0.02	0.037	-9999	-0.57	2	2
TFPI	-0.034	0.16	-9999	-0.84	34	34
F2	0.001	0.028	-9999	-10000	0	0
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.16	0.24	-9999	-0.56	125	125
ACTN1	-0.001	0.029	-9999	-0.84	1	1
TNC	-0.019	0.12	-9999	-0.69	23	23
Syndecan-4/CXCL12	-0.053	0.12	-9999	-0.48	29	29
FGF6	-0.002	0.041	-9999	-0.84	2	2
RHOA	0	0	-9999	-10000	0	0
CXCL12	-0.062	0.22	-9999	-0.84	62	62
TNFRSF13B	-0.024	0.12	-9999	-0.84	13	13
FGF2	-0.34	0.41	-9999	-0.84	337	337
FGFR1	-0.008	0.077	-9999	-0.71	9	9
Syndecan-4/PI-4-5-P2	-0.014	0.044	-9999	-0.67	1	1
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.12	0.15	-9999	-0.29	370	370
cell migration	-0.025	0.019	-9999	-10000	0	0
PRKCD	0.004	0.014	-9999	-10000	0	0
vasculogenesis	-0.019	0.035	-9999	-0.63	1	1
SDC4	-0.014	0.047	-9999	-0.71	1	1
Syndecan-4/Tenascin C	-0.03	0.076	-9999	-0.53	11	11
Syndecan-4/PI-4-5-P2/PKC alpha	-0.044	0.035	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.019	0.033	-9999	-0.66	1	1
MMP9	-0.11	0.14	-9999	-0.28	348	348
Rac1/GTP	-0.028	0.059	-9999	-0.37	21	21
cytoskeleton organization	-0.019	0.033	-9999	-0.63	1	1
GIPC1	0	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.038	0.094	-9999	-0.53	9	9

×

Insulin-mediated glucose transport

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.13	0.12	-9999	-0.38	14	14
CaM/Ca2+	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
AKT2	0	0	-9999	-10000	0	0
STXBP4	-0.001	0.014	-9999	-0.28	2	2
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	-0.13	0.15	-9999	-0.26	472	472
YWHAZ	-0.001	0.017	-9999	-0.28	3	3
CALM1	0	0	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
TBC1D4	0.021	0.023	-9999	-0.65	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
SNARE/Synip	0	0.007	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
ASIP	-0.001	0.017	-9999	-0.28	3	3
PRKCI	0	0.01	-9999	-0.28	1	1
AS160/CaM/Ca2+	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
GYS1	0	0	-9999	-10000	0	0
PRKCZ	-0.001	0.029	-9999	-0.84	1	1
TRIP10	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
AS160/14-3-3	-0.004	0.032	-9999	-10000	0	0
VAMP2	0	0	-9999	-10000	0	0
SLC2A4	-0.14	0.16	-9999	-0.28	472	472
STX4	0	0	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
SFN	-0.016	0.11	-9999	-0.62	21	21
LNPEP	-0.004	0.058	-9999	-0.84	4	4
YWHAE	0	0	-9999	-10000	0	0

×

Nectin adhesion pathway

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
PDGFRB	-0.002	0.041	-9999	-0.84	2	2
alphaV beta3 Integrin	-0.012	0.083	-9999	-0.64	14	14
PTK2	-0.047	0.16	-9999	-0.56	68	68
positive regulation of JNK cascade	-0.028	0.093	-9999	-0.34	68	68
CDC42/GDP	0.013	0.14	-9999	-0.46	68	68
Rac1/GDP	0.015	0.14	-9999	-0.45	68	68
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.034	0.12	-9999	-0.42	68	68
nectin-3/I-afadin	-0.053	0.18	-9999	-0.66	68	68
RAPGEF1	0.008	0.16	-9999	-0.52	68	68
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.004	0.18	-9999	-0.61	68	68
PDGFB-D/PDGFRB	-0.002	0.041	-9999	-0.84	2	2
TLN1	-0.024	0.089	-9999	-0.7	6	6
Rap1/GTP	-0.03	0.099	-9999	-0.36	68	68
IQGAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.002	0.031	-9999	-0.52	3	3
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.053	0.18	-9999	-0.66	68	68
PVR	0	0	-9999	-10000	0	0
Necl-5(dimer)	0	0	-9999	-10000	0	0
mol:GDP	0.006	0.17	-9999	-0.58	68	68
MLLT4	-0.003	0.05	-9999	-0.84	3	3
PIK3CA	0	0.01	-9999	-10000	0	0
PI3K	-0.041	0.14	-9999	-0.49	70	70
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.002	0.038	-9999	-0.64	3	3
positive regulation of lamellipodium assembly	-0.029	0.097	-9999	-0.36	68	68
PVRL1	0	0	-9999	-10000	0	0
PVRL3	-0.067	0.23	-9999	-0.84	67	67
PVRL2	-0.001	0.017	-9999	-0.28	3	3
PIK3R1	0	0	-9999	-10000	0	0
CDH1	-0.024	0.14	-9999	-0.84	24	24
CLDN1	-0.04	0.16	-9999	-0.6	56	56
JAM-A/CLDN1	-0.064	0.18	-9999	-0.56	93	93
SRC	-0.057	0.19	-9999	-0.69	68	68
ITGB3	-0.015	0.11	-9999	-0.84	14	14
nectin-1(dimer)/I-afadin/I-afadin	-0.002	0.038	-9999	-0.64	3	3
FARP2	0	0.17	-9999	-0.57	68	68
RAC1	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.046	0.16	-9999	-0.57	68	68
nectin-1/I-afadin	-0.002	0.038	-9999	-0.64	3	3
nectin-2/I-afadin	-0.003	0.04	-9999	-0.64	3	3
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.046	0.16	-9999	-0.57	68	68
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.028	0.093	-9999	-0.34	68	68
alphaV/beta3 Integrin/Talin	-0.027	0.11	-9999	-0.64	17	17
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.003	0.04	-9999	-0.64	3	3
nectin-2(dimer)/I-afadin/I-afadin	-0.003	0.04	-9999	-0.64	3	3
PIP5K1C	-0.026	0.096	-9999	-0.66	8	8
VAV2	-0.001	0.17	-9999	-0.58	68	68
RAP1/GDP	-0.035	0.12	-9999	-0.42	68	68
ITGAV	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.047	0.16	-9999	-0.57	68	68
nectin-3(dimer)/I-afadin/I-afadin	-0.053	0.18	-9999	-0.66	68	68
Rac1/GTP	-0.036	0.12	-9999	-0.44	68	68
PTPRM	-0.029	0.11	-9999	-0.34	71	71
E-cadherin/beta catenin/alpha catenin	-0.015	0.08	-9999	-0.45	27	27
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.035	0.13	-10000	0	-0.61	32	32
FYN	0.017	0.18	-10000	0	-0.77	33	33
LAT/GRAP2/SLP76	-0.027	0.15	-10000	0	-0.64	37	37
IKBKB	-0.001	0.014	-10000	0	-0.28	2	2
AKT1	0.032	0.12	-10000	0	-0.47	35	35
B2M	0.008	0.006	-10000	0	-10000	0	0
IKBKG	-0.008	0.027	-10000	0	-0.14	8	8
MAP3K8	-0.005	0.065	-10000	0	-0.74	6	6
mol:Ca2+	-0.028	0.051	-10000	0	-0.12	175	175
integrin-mediated signaling pathway	-0.002	0.028	-10000	0	-0.56	2	2
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.023	0.18	-10000	0	-0.7	38	38
TRPV6	-0.18	0.34	-10000	0	-0.85	175	175
CD28	-0.006	0.063	-10000	0	-0.84	4	4
SHC1	0.011	0.19	-10000	0	-0.79	34	34
receptor internalization	-0.001	0.21	-10000	0	-0.7	51	51
PRF1	-0.002	0.23	-10000	0	-1.2	25	25
KRAS	0	0.01	-10000	0	-10000	0	0
GRB2	0	0.01	-10000	0	-10000	0	0
COT/AKT1	0.033	0.1	-10000	0	-0.38	36	36
LAT	0.01	0.19	-10000	0	-0.77	38	38
EntrezGene:6955	0.001	0.003	-10000	0	-10000	0	0
CD3D	-0.023	0.14	-10000	0	-0.52	50	50
CD3E	-0.018	0.14	-10000	0	-0.85	21	21
CD3G	-0.038	0.16	-10000	0	-0.53	61	61
RASGRP2	-0.006	0.04	-10000	0	-0.19	37	37
RASGRP1	0.038	0.12	-10000	0	-0.46	37	37
HLA-A	0.01	0.015	-10000	0	-10000	0	0
RASSF5	-0.002	0.042	-10000	0	-0.65	3	3
RAP1A/GTP/RAPL	-0.002	0.028	-10000	0	-0.57	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.034	0.042	-10000	0	-0.12	32	32
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.014	0.048	-10000	0	-0.24	23	23
PRKCA	-0.011	0.087	-10000	0	-0.31	49	49
GRAP2	-0.014	0.1	-10000	0	-0.73	16	16
mol:IP3	0.024	0.15	0.28	149	-0.45	35	184
EntrezGene:6957	0.001	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.007	0.22	-10000	0	-0.96	31	31
ORAI1	0.085	0.16	0.39	175	-10000	0	175
CSK	0.009	0.19	-10000	0	-0.81	34	34
B7 family/CD28	-0.019	0.18	-10000	0	-0.74	39	39
CHUK	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.002	0.22	-10000	0	-0.81	46	46
PTPN6	0.008	0.19	-10000	0	-0.71	43	43
VAV1	0.011	0.19	-10000	0	-0.69	44	44
Monovalent TCR/CD3	-0.029	0.21	-10000	0	-0.73	49	49
CBL	0	0	-10000	0	-10000	0	0
LCK	0.01	0.2	-10000	0	-0.71	45	45
PAG1	0.008	0.19	-10000	0	-0.7	44	44
RAP1A	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.002	0.22	-10000	0	-0.82	43	43
CD80	-0.08	0.12	-10000	0	-0.28	12	12
CD86	-0.001	0.019	-10000	0	-0.28	4	4
PDK1/CARD11/BCL10/MALT1	-0.017	0.058	-10000	0	-0.28	28	28
HRAS	0	0.01	-10000	0	-10000	0	0
GO:0035030	-0.045	0.13	-10000	0	-0.59	39	39
CD8A	-0.004	0.08	-10000	0	-0.39	26	26
CD8B	-0.026	0.16	-10000	0	-0.6	51	51
PTPRC	-0.007	0.06	-10000	0	-0.39	15	15
PDK1/PKC theta	0.036	0.16	-10000	0	-0.6	38	38
CSK/PAG1	0.013	0.18	-10000	0	-0.79	33	33
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	0	0.008	-10000	0	-10000	0	0
GRAP2/SLP76	-0.034	0.17	-10000	0	-0.74	39	39
STIM1	0.045	0.083	-10000	0	-10000	0	0
RAS family/GTP	0.042	0.053	-10000	0	-0.18	24	24
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.005	0.23	-10000	0	-0.78	51	51
mol:DAG	-0.005	0.1	-10000	0	-0.41	35	35
RAP1A/GDP	0.016	0.018	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
CD247	-0.022	0.13	-10000	0	-0.62	30	30
cytotoxic T cell degranulation	0.001	0.21	-10000	0	-1.1	27	27
RAP1A/GTP	-0.003	0.014	-10000	0	-0.068	28	28
mol:PI-3-4-5-P3	0.028	0.14	-10000	0	-0.55	38	38
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.017	0.18	0.29	144	-0.61	35	179
NRAS	-0.001	0.014	-10000	0	-10000	0	0
ZAP70	-0.027	0.13	-10000	0	-0.51	44	44
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.024	0.14	-10000	0	-0.63	35	35
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.035	0.15	-10000	0	-0.62	43	43
CARD11	-0.007	0.056	-10000	0	-0.84	2	2
PRKCB	-0.01	0.086	-10000	0	-0.32	42	42
PRKCE	-0.005	0.07	-10000	0	-0.28	33	33
PRKCQ	0.026	0.18	-10000	0	-0.68	40	40
LCP2	0	0.01	-10000	0	-0.28	1	1
BCL10	0	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.033	0.1	-10000	0	-0.4	35	35
IKK complex	0.042	0.044	-10000	0	-0.12	26	26
RAS family/GDP	-0.002	0.006	-10000	0	-10000	0	0
MAP3K14	0.037	0.08	-10000	0	-0.3	30	30
PDPK1	0.035	0.12	-10000	0	-0.45	34	34
TCR/CD3/MHC I/CD8/Fyn	-0.007	0.24	-10000	0	-0.96	41	41

×

Glypican 2 network

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
MDK	-0.01	0.051	-9999	-10000	0	0
GPC2	-0.033	0.099	-9999	-0.3	94	94
GPC2/Midkine	-0.027	0.077	-9999	-0.41	15	15
neuron projection morphogenesis	-0.027	0.077	-9999	-0.41	15	15

×

Canonical Wnt signaling pathway

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.004	0.017	-10000	0	-10000	0	0
AES	0.003	0.014	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0.009	-10000	0	-10000	0	0
SMAD4	0	0	-10000	0	-10000	0	0
DKK2	-0.018	0.12	-10000	0	-0.78	19	19
TLE1	-0.003	0.072	-10000	0	-0.84	6	6
MACF1	0	0	-10000	0	-10000	0	0
CTNNB1	0.11	0.088	-10000	0	-10000	0	0
WIF1	-0.44	0.42	-10000	0	-0.84	440	440
beta catenin/RanBP3	0.013	0.075	0.38	30	-10000	0	30
KREMEN2	-0.13	0.14	-10000	0	-0.28	389	389
DKK1	-0.08	0.2	-10000	0	-0.84	43	43
beta catenin/beta TrCP1	0.1	0.087	-10000	0	-10000	0	0
FZD1	0	0	-10000	0	-10000	0	0
AXIN2	-0.007	0.18	-10000	0	-1.6	11	11
AXIN1	0	0.002	-10000	0	-10000	0	0
RAN	0	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.004	0.017	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.095	0.073	-10000	0	-0.53	3	3
Axin1/APC/GSK3	0.001	0.015	0.24	1	-10000	0	1
Axin1/APC/GSK3/beta catenin/Macf1	0.078	0.034	-10000	0	-10000	0	0
HNF1A	0.001	0.029	-10000	0	-0.28	6	6
CTBP1	0.004	0.015	-10000	0	-10000	0	0
MYC	-0.021	0.24	-10000	0	-1.6	20	20
RANBP3	0	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.074	0.11	-10000	0	-0.66	17	17
NKD1	-0.011	0.08	-10000	0	-0.43	22	22
TCF4	-0.001	0.067	-10000	0	-0.84	5	5
TCF3	0.004	0.015	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0	0.006	-10000	0	-10000	0	0
Ran/GTP	0	0	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.013	0.094	0.44	34	-0.44	1	35
LEF1	-0.037	0.1	-10000	0	-10000	0	0
DVL1	0.073	0.066	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.1	0.082	-10000	0	-0.58	2	2
DKK1/LRP6/Kremen 2	-0.11	0.15	-10000	0	-0.6	45	45
LRP6	-0.001	0.014	-10000	0	-10000	0	0
CSNK1A1	0.004	0.017	-10000	0	-10000	0	0
NLK	0	0.01	-10000	0	-10000	0	0
CCND1	0.002	0.11	-10000	0	-1.6	3	3
WNT1	0	0.01	-10000	0	-0.28	1	1
GSK3A	0	0	-10000	0	-10000	0	0
GSK3B	0	0	-10000	0	-10000	0	0
FRAT1	0	0	-10000	0	-10000	0	0
PPP2R5D	0.045	0.048	0.35	7	-10000	0	7
APC	0	0.005	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.15	0.14	0.28	440	-10000	0	440
CREBBP	0.004	0.015	-10000	0	-10000	0	0

×

IL27-mediated signaling events

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.002	0.007	-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	0.014	0.1	0.44	17	-10000	0	17
IL27/IL27R/JAK1	-0.046	0.16	-10000	0	-0.63	29	29
TBX21	-0.024	0.2	-10000	0	-0.63	54	54
IL12B	-0.052	0.11	-10000	0	-0.28	71	71
IL12A	-0.031	0.16	-10000	0	-0.66	48	48
IL6ST	-0.051	0.21	-10000	0	-0.84	56	56
IL27RA/JAK1	-0.006	0.068	-10000	0	-1.4	2	2
IL27	-0.023	0.084	-10000	0	-0.28	82	82
TYK2	0.008	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.14	0.18	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.014	0.1	0.44	17	-10000	0	17
T cell proliferation during immune response	0.014	0.1	0.44	17	-10000	0	17
MAPKKK cascade	-0.014	0.1	-10000	0	-0.44	17	17
STAT3	0	0	-10000	0	-10000	0	0
STAT2	0	0	-10000	0	-10000	0	0
STAT1	-0.006	0.041	-10000	0	-10000	0	0
IL12RB1	-0.009	0.056	-10000	0	-0.3	26	26
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.039	0.22	-10000	0	-0.63	66	66
IL27/IL27R/JAK2/TYK2	-0.017	0.1	-10000	0	-0.44	17	17
positive regulation of T cell mediated cytotoxicity	-0.014	0.1	-10000	0	-0.44	17	17
STAT1 (dimer)	-0.064	0.2	0.47	19	-0.73	31	50
JAK2	0.004	0.006	-10000	0	-10000	0	0
JAK1	0	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	-0.028	0.089	-10000	0	-0.45	11	11
T cell proliferation	-0.19	0.25	-10000	0	-0.49	331	331
IL12/IL12R/TYK2/JAK2	0.013	0.071	-10000	0	-10000	0	0
IL17A	-0.14	0.18	-10000	0	-10000	0	0
mast cell activation	0.014	0.1	0.44	17	-10000	0	17
IFNG	0.003	0.021	-10000	0	-0.078	4	4
T cell differentiation	-0.003	0.005	-10000	0	-0.02	11	11
STAT3 (dimer)	-0.028	0.089	-10000	0	-0.49	7	7
STAT5A (dimer)	-0.032	0.1	-10000	0	-0.55	12	12
STAT4 (dimer)	-0.047	0.13	-10000	0	-0.53	41	41
STAT4	-0.033	0.16	-10000	0	-0.82	34	34
T cell activation	-0.008	0.008	0.13	2	-10000	0	2
IL27R/JAK2/TYK2	-0.036	0.14	-10000	0	-0.57	34	34
GATA3	-0.044	0.28	-10000	0	-1.5	30	30
IL18	0.006	0.032	-10000	0	-10000	0	0
positive regulation of mast cell cytokine production	-0.027	0.087	-10000	0	-0.48	7	7
IL27/EBI3	-0.022	0.074	-10000	0	-0.57	7	7
IL27RA	0.001	0.074	-10000	0	-1.5	2	2
IL6	-0.32	0.41	-10000	0	-0.84	323	323
STAT5A	-0.007	0.076	-10000	0	-0.84	7	7
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.002	0.028	0.48	2	-10000	0	2
IL1B	0.003	0.069	-10000	0	-0.66	9	9
EBI3	-0.003	0.07	-10000	0	-0.54	11	11
TNF	-0.001	0.077	-10000	0	-0.66	10	10

×

IL12-mediated signaling events

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.002	0.13	-10000	0	-0.41	42	42
TBX21	-0.01	0.35	-10000	0	-1.2	46	46
B2M	0.01	0.005	-10000	0	-10000	0	0
TYK2	0.017	0.015	-10000	0	-10000	0	0
IL12RB1	0.007	0.062	-10000	0	-0.31	26	26
GADD45B	0.038	0.21	-10000	0	-0.79	25	25
IL12RB2	-0.058	0.2	-10000	0	-0.48	115	115
GADD45G	0.034	0.21	-10000	0	-0.79	25	25
natural killer cell activation	0.007	0.017	-10000	0	-10000	0	0
RELB	-0.002	0.021	-10000	0	-0.28	5	5
RELA	0	0	-10000	0	-10000	0	0
IL18	0.007	0.047	-10000	0	-0.27	22	22
IL2RA	-0.028	0.11	-10000	0	-0.36	66	66
IFNG	-0.041	0.099	-10000	0	-0.28	124	124
STAT3 (dimer)	0.032	0.21	-10000	0	-0.63	40	40
HLA-DRB5	-0.022	0.093	-10000	0	-0.42	23	23
FASLG	0.015	0.26	-10000	0	-1	27	27
NF kappa B2 p52/RelB	-0.074	0.18	-10000	0	-0.69	48	48
CD4	0	0	-10000	0	-10000	0	0
SOCS1	-0.004	0.039	-10000	0	-0.34	9	9
EntrezGene:6955	-0.007	0.014	-10000	0	-10000	0	0
CD3D	-0.023	0.14	-10000	0	-0.52	50	50
CD3E	-0.022	0.14	-10000	0	-0.8	23	23
CD3G	-0.031	0.16	-10000	0	-0.54	61	61
IL12Rbeta2/JAK2	-0.027	0.16	-10000	0	-0.66	40	40
CCL3	0.019	0.25	-10000	0	-0.9	33	33
CCL4	0.022	0.24	-10000	0	-0.94	24	24
HLA-A	0.009	0.015	-10000	0	-10000	0	0
IL18/IL18R	0.024	0.15	-10000	0	-0.59	42	42
NOS2	0.025	0.24	-10000	0	-0.97	24	24
IL12/IL12R/TYK2/JAK2/SPHK2	-0.001	0.13	-10000	0	-0.36	66	66
IL1R1	0.013	0.27	-10000	0	-1.1	31	31
IL4	-0.005	0.018	-10000	0	-10000	0	0
JAK2	0.017	0.015	-10000	0	-10000	0	0
EntrezGene:6957	-0.006	0.012	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.031	0.26	-10000	0	-1.1	36	36
RAB7A	0.054	0.19	-10000	0	-0.68	22	22
lysosomal transport	0.055	0.18	-10000	0	-0.64	22	22
FOS	-0.39	0.69	-10000	0	-1.3	283	283
STAT4 (dimer)	0.028	0.26	-10000	0	-0.88	38	38
STAT5A (dimer)	-0.077	0.2	-10000	0	-0.68	55	55
GZMA	0.01	0.27	-10000	0	-1.1	25	25
GZMB	-0.002	0.3	-10000	0	-1.1	35	35
HLX	0	0.01	-10000	0	-0.28	1	1
LCK	0.013	0.27	-10000	0	-0.77	58	58
TCR/CD3/MHC II/CD4	-0.068	0.2	-10000	0	-0.59	61	61
IL2/IL2R	-0.028	0.098	-10000	0	-0.47	31	31
MAPK14	0.044	0.22	-10000	0	-0.76	29	29
CCR5	0.032	0.22	-10000	0	-0.82	25	25
IL1B	0.007	0.092	-10000	0	-0.74	11	11
STAT6	0.027	0.085	-10000	0	-0.24	12	12
STAT4	-0.033	0.16	-10000	0	-0.82	34	34
STAT3	0	0	-10000	0	-10000	0	0
STAT1	-0.006	0.04	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
NFKB2	0	0	-10000	0	-10000	0	0
IL12B	-0.038	0.11	-10000	0	-0.29	74	74
CD8A	-0.002	0.08	-10000	0	-0.39	26	26
CD8B	-0.026	0.16	-10000	0	-0.6	51	51
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.002	0.13	0.41	42	-10000	0	42
IL2RB	-0.011	0.055	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.24	-10000	0	-0.78	38	38
IL2RG	-0.016	0.083	-10000	0	-0.84	5	5
IL12	-0.049	0.17	-10000	0	-0.63	52	52
STAT5A	-0.007	0.076	-10000	0	-0.84	7	7
CD247	-0.014	0.13	-10000	0	-0.62	30	30
IL2	-0.003	0.029	-10000	0	-10000	0	0
SPHK2	0	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.036	0.2	-10000	0	-0.78	54	54
IL12/IL12R/TYK2/JAK2	0.017	0.27	-10000	0	-0.77	54	54
MAP2K3	0.04	0.22	-10000	0	-0.79	27	27
RIPK2	-0.001	0.019	-10000	0	-0.28	4	4
MAP2K6	0.036	0.22	-10000	0	-0.75	33	33
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.002	0.032	-10000	0	-0.57	2	2
IL18RAP	-0.02	0.17	-10000	0	-0.81	35	35
IL12Rbeta1/TYK2	0.016	0.05	-10000	0	-0.7	1	1
EOMES	-0.023	0.18	-10000	0	-1.5	12	12
STAT1 (dimer)	0.036	0.21	-10000	0	-0.63	37	37
T cell proliferation	0.038	0.2	-10000	0	-0.62	39	39
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.004	0.097	-10000	0	-0.84	11	11
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.059	0.17	-10000	0	-0.73	35	35
ATF2	0.052	0.2	-10000	0	-0.72	27	27

×

Coregulation of Androgen receptor activity

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
NRIP1	-0.008	0.034	-10000	0	-0.84	1	1
SVIL	-0.009	0.052	-10000	0	-0.84	3	3
ZNF318	0.022	0.058	-10000	0	-10000	0	0
JMJD2C	-0.004	0.043	-10000	0	-0.13	81	81
T-DHT/AR/Ubc9	-0.075	0.18	-10000	0	-0.58	92	92
CARM1	0	0	-10000	0	-10000	0	0
PRDX1	0.002	0.007	-10000	0	-10000	0	0
PELP1	0.005	0.012	-10000	0	-10000	0	0
CTNNB1	-0.005	0.012	-10000	0	-10000	0	0
AKT1	0.007	0.018	-10000	0	-10000	0	0
PTK2B	-0.004	0.01	-10000	0	-10000	0	0
MED1	0	0.049	-10000	0	-10000	0	0
MAK	0.011	0.1	0.22	1	-0.54	16	17
response to oxidative stress	0.001	0.004	-10000	0	-10000	0	0
HIP1	-0.006	0.017	-10000	0	-10000	0	0
GSN	-0.02	0.1	-10000	0	-0.84	13	13
NCOA2	-0.007	0.076	-10000	0	-0.84	7	7
NCOA6	-0.002	0.021	-10000	0	-10000	0	0
DNA-PK	0.021	0.059	-10000	0	-10000	0	0
NCOA4	0	0	-10000	0	-10000	0	0
PIAS3	-0.005	0.012	-10000	0	-10000	0	0
cell proliferation	-0.006	0.1	-10000	0	-0.86	8	8
XRCC5	0.006	0.016	-10000	0	-10000	0	0
UBE3A	-0.006	0.031	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.09	0.21	-10000	0	-0.62	106	106
FHL2	-0.018	0.12	-10000	0	-1.2	5	5
RANBP9	-0.001	0.018	-10000	0	-10000	0	0
JMJD1A	-0.012	0.057	-10000	0	-0.15	121	121
CDK6	-0.005	0.072	-10000	0	-0.84	6	6
TGFB1I1	-0.009	0.052	-10000	0	-0.84	3	3
T-DHT/AR/CyclinD1	-0.087	0.19	-10000	0	-0.58	98	98
XRCC6	0.006	0.016	-10000	0	-10000	0	0
T-DHT/AR	-0.063	0.21	-10000	0	-0.56	107	107
CTDSP1	0	0	-10000	0	-10000	0	0
CTDSP2	0.015	0.039	-10000	0	-10000	0	0
BRCA1	-0.007	0.023	-10000	0	-0.32	2	2
TCF4	0.006	0.071	-10000	0	-0.82	5	5
CDKN2A	-0.035	0.1	-10000	0	-0.28	115	115
SRF	0.023	0.02	-10000	0	-10000	0	0
NKX3-1	-0.083	0.2	-10000	0	-1.3	17	17
KLK3	-0.18	0.52	-10000	0	-1.6	102	102
TMF1	0	0	-10000	0	-10000	0	0
HNRNPA1	0.008	0.022	-10000	0	-10000	0	0
AOF2	-0.008	0.024	-10000	0	-0.072	102	102
APPL1	0.034	0.033	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.067	0.19	-10000	0	-0.57	93	93
AR	-0.09	0.27	-10000	0	-0.84	93	93
UBA3	0	0	-10000	0	-10000	0	0
PATZ1	0.008	0.022	-10000	0	-10000	0	0
PAWR	0	0	-10000	0	-10000	0	0
PRKDC	0.004	0.025	-10000	0	-0.28	4	4
PA2G4	0.011	0.028	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.063	0.17	-10000	0	-0.53	93	93
RPS6KA3	-0.009	0.045	-10000	0	-0.84	2	2
T-DHT/AR/ARA70	-0.079	0.18	-10000	0	-0.58	92	92
LATS2	0.009	0.023	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.058	0.18	0.19	1	-0.53	92	93
Cyclin D3/CDK11 p58	0	0	-10000	0	-10000	0	0
VAV3	-0.013	0.064	-10000	0	-0.37	19	19
KLK2	-0.13	0.34	-10000	0	-1.2	70	70
CASP8	0.004	0.011	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.075	0.17	-10000	0	-0.54	97	97
TMPRSS2	-0.18	0.4	-10000	0	-1.2	112	112
CCND1	-0.016	0.074	-10000	0	-0.33	36	36
PIAS1	-0.006	0.031	-10000	0	-10000	0	0
mol:T-DHT	-0.01	0.035	-10000	0	-0.08	157	157
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.012	0.05	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.076	0.19	-10000	0	-0.58	98	98
CMTM2	0.003	0.013	-10000	0	-10000	0	0
SNURF	-0.023	0.14	-10000	0	-0.84	23	23
ZMIZ1	0.002	0.032	-10000	0	-0.35	1	1
CCND3	0.002	0.005	-10000	0	-10000	0	0
TGIF1	0.008	0.022	-10000	0	-10000	0	0
FKBP4	-0.004	0.031	-10000	0	-10000	0	0

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	0.028	0.026	-9999	-10000	0	0
BUB1B	-0.039	0.046	-9999	-10000	0	0
PLK1	-0.007	0.021	-9999	-10000	0	0
PLK1S1	0	0.012	-9999	-10000	0	0
KIF2A	0.003	0.019	-9999	-10000	0	0
regulation of mitotic centrosome separation	-0.007	0.021	-9999	-10000	0	0
GOLGA2	0	0	-9999	-10000	0	0
Hec1/SPC24	-0.16	0.11	-9999	-0.27	335	335
WEE1	-0.002	0.021	-9999	-10000	0	0
cytokinesis	-0.045	0.042	-9999	-0.27	2	2
PP2A-alpha B56	0.036	0.022	-9999	-10000	0	0
AURKA	0.003	0.011	-9999	-10000	0	0
PICH/PLK1	-0.078	0.092	-9999	-0.32	10	10
CENPE	-0.056	0.083	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.003	0.019	-9999	-10000	0	0
PPP2CA	0	0	-9999	-10000	0	0
FZR1	0	0	-9999	-10000	0	0
TPX2	-0.002	0.013	-9999	-10000	0	0
PAK1	-0.006	0.04	-9999	-0.27	18	18
SPC24	-0.17	0.14	-9999	-0.28	518	518
FBXW11	0	0	-9999	-10000	0	0
CLSPN	-0.003	0.014	-9999	-10000	0	0
GORASP1	0	0	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	-0.004	0.012	-9999	-10000	0	0
G2 phase of mitotic cell cycle	-0.002	0.002	-9999	-10000	0	0
STAG2	0	0	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.008	0.009	-9999	-10000	0	0
spindle elongation	-0.007	0.021	-9999	-10000	0	0
ODF2	0	0	-9999	-10000	0	0
BUB1	0.031	0.019	-9999	-10000	0	0
TPT1	0	0.012	-9999	-10000	0	0
CDC25C	-0.001	0.012	-9999	-10000	0	0
CDC25B	-0.003	0.038	-9999	-10000	0	0
SGOL1	-0.028	0.026	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.022	0.041	-9999	-10000	0	0
CDC14B	-0.01	0.12	-9999	-0.66	25	25
CDC20	-0.16	0.14	-9999	-10000	0	0
PLK1/PBIP1	-0.031	0.054	-9999	-10000	0	0
mitosis	-0.007	0.007	-9999	-0.022	2	2
FBXO5	0	0.021	-9999	-10000	0	0
CDC2	-0.001	0.002	-9999	-10000	0	0
NDC80	-0.18	0.13	-9999	-10000	0	0
metaphase plate congression	-0.002	0.014	-9999	-10000	0	0
ERCC6L	-0.068	0.084	-9999	-10000	0	0
NLP/gamma Tubulin	0	0.012	-9999	-10000	0	0
microtubule cytoskeleton organization	0	0.012	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	-0.001	0.001	-9999	-10000	0	0
PPP1R12A	0	0	-9999	-10000	0	0
interphase	-0.001	0.001	-9999	-10000	0	0
PLK1/PRC1-2	-0.14	0.094	-9999	-0.27	237	237
GRASP65/GM130/RAB1/GTP/PLK1	-0.001	0.002	-9999	-10000	0	0
RAB1A	0	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	-0.002	0.022	-9999	-10000	0	0
mitotic prometaphase	-0.002	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.011	0.05	-9999	-0.3	20	20
microtubule-based process	-0.12	0.059	-9999	-0.18	7	7
Golgi organization	-0.007	0.021	-9999	-10000	0	0
Cohesin/SA2	-0.008	0.009	-9999	-10000	0	0
PPP1CB/MYPT1	0	0	-9999	-10000	0	0
KIF20A	-0.22	0.11	-9999	-0.28	676	676
APC/C/CDC20	-0.085	0.075	-9999	-10000	0	0
PPP2R1A	0	0	-9999	-10000	0	0
chromosome segregation	-0.03	0.053	-9999	-10000	0	0
PRC1	-0.078	0.12	-9999	-0.28	237	237
ECT2	-0.004	0.039	-9999	-0.2	2	2
C13orf34	0	0.02	-9999	-10000	0	0
NUDC	-0.002	0.014	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.039	0.046	-9999	-10000	0	0
spindle assembly	-0.003	0.018	-9999	-10000	0	0
spindle stabilization	0	0.012	-9999	-10000	0	0
APC/C/HCDH1	-0.017	0.097	-9999	-0.57	25	25
MKLP2/PLK1	-0.12	0.059	-9999	-0.18	7	7
CCNB1	-0.065	0.12	-9999	-0.28	195	195
PPP1CB	0	0	-9999	-10000	0	0
BTRC	0	0	-9999	-10000	0	0
ROCK2	0.005	0.031	-9999	-0.55	2	2
TUBG1	0	0.012	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.022	0.039	-9999	-10000	0	0
MLF1IP	-0.032	0.077	-9999	-10000	0	0
INCENP	0	0	-9999	-10000	0	0

×

Regulation of Androgen receptor activity

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
HDAC1	0.02	0.006	-9999	-10000	0	0
SMARCC1	0.004	0.022	-9999	-0.59	1	1
REL	0.003	0.031	-9999	-0.84	1	1
HDAC7	0.012	0.12	-9999	-0.64	6	6
JUN	-0.009	0.086	-9999	-0.84	9	9
EP300	0	0	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
KAT5	0.001	0.004	-9999	-10000	0	0
MAPK14	0.005	0.098	-9999	-0.65	18	18
FOXO1	-0.006	0.07	-9999	-0.84	6	6
T-DHT/AR	-0.002	0.13	-9999	-0.57	11	11
MAP2K6	-0.018	0.12	-9999	-0.81	19	19
BRM/BAF57	-0.001	0.009	-9999	-10000	0	0
MAP2K4	0	0.029	-9999	-0.84	1	1
SMARCA2	0	0	-9999	-10000	0	0
PDE9A	-0.093	0.3	-9999	-1.1	64	64
NCOA2	-0.007	0.076	-9999	-0.84	7	7
CEBPA	-0.006	0.076	-9999	-0.84	7	7
EHMT2	0	0	-9999	-10000	0	0
cell proliferation	0.021	0.14	-9999	-0.53	12	12
NR0B1	-0.01	0.052	-9999	-10000	0	0
EGR1	-0.29	0.4	-9999	-0.84	287	287
RXRs/9cRA	-0.13	0.22	-9999	-0.52	204	204
AR/RACK1/Src	-0.002	0.1	-9999	-0.54	12	12
AR/GR	-0.043	0.11	-9999	-0.43	30	30
GNB2L1	0.001	0.003	-9999	-10000	0	0
PKN1	0	0	-9999	-10000	0	0
RCHY1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.001	0.003	-9999	-10000	0	0
MAPK8	0.019	0.027	-9999	-0.65	1	1
T-DHT/AR/TIF2/CARM1	-0.029	0.096	-9999	-0.51	21	21
SRC	0.024	0.088	-9999	-0.51	18	18
NR3C1	-0.007	0.076	-9999	-0.84	7	7
KLK3	-0.21	0.42	-9999	-1.2	119	119
APPBP2	-0.001	0.013	-9999	-0.27	2	2
TRIM24	0	0.01	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.024	0.088	-9999	-0.52	18	18
TMPRSS2	-0.17	0.43	-9999	-1.2	112	112
RXRG	-0.2	0.36	-9999	-0.84	204	204
mol:9cRA	-0.001	0.002	-9999	-10000	0	0
RXRA	0	0	-9999	-10000	0	0
RXRB	0	0	-9999	-10000	0	0
CARM1	0	0	-9999	-10000	0	0
NR2C2	0	0	-9999	-10000	0	0
KLK2	-0.035	0.25	-9999	-0.81	72	72
AR	-0.02	0.13	-9999	-0.34	101	101
SENP1	0	0	-9999	-10000	0	0
HSP90AA1	0	0.01	-9999	-0.28	1	1
MDM2	0.004	0.024	-9999	-0.28	4	4
SRY	0.003	0.01	-9999	-10000	0	0
GATA2	-0.023	0.13	-9999	-0.84	19	19
MYST2	0	0.01	-9999	-0.28	1	1
HOXB13	-0.13	0.14	-9999	-0.28	384	384
T-DHT/AR/RACK1/Src	-0.024	0.086	-9999	-0.54	12	12
positive regulation of transcription	-0.023	0.13	-9999	-0.84	19	19
DNAJA1	0	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.005	0.013	-9999	-10000	0	0
NCOA1	0.011	0.031	-9999	-0.87	1	1
SPDEF	-0.047	0.2	-9999	-0.81	50	50
T-DHT/AR/TIF2	0.026	0.067	-9999	-0.38	3	3
T-DHT/AR/Hsp90	-0.03	0.084	-9999	-0.52	18	18
GSK3B	0.001	0.004	-9999	-10000	0	0
NR2C1	0.002	0.006	-9999	-10000	0	0
mol:T-DHT	0.017	0.092	-9999	-0.55	18	18
SIRT1	0	0	-9999	-10000	0	0
ZMIZ2	0.005	0.013	-9999	-10000	0	0
POU2F1	0.02	0.027	-9999	-0.41	1	1
T-DHT/AR/DAX-1	-0.031	0.089	-9999	-0.53	18	18
CREBBP	0	0	-9999	-10000	0	0
SMARCE1	-0.001	0.014	-9999	-0.28	2	2

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.018	0.12	-9999	-0.84	18	18
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	-0.001	0.029	-9999	-0.84	1	1
RAC1-CDC42/GTP/PAK family	-0.13	0.14	-9999	-0.28	377	377
response to UV	0	0	-9999	-10000	0	0
YES1	-0.001	0.029	-9999	-0.84	1	1
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0	0	-9999	-10000	0	0
FYN	-0.001	0.029	-9999	-0.84	1	1
MAP3K12	0	0	-9999	-10000	0	0
FGR	0	0.01	-9999	-0.28	1	1
p38 alpha/TAB1	-0.007	0.035	-9999	-0.38	2	2
PRKG1	-0.032	0.16	-9999	-0.84	32	32
DUSP8	-0.003	0.051	-9999	-0.7	4	4
PGK/cGMP/p38 alpha	-0.022	0.088	-9999	-0.43	34	34
apoptosis	-0.007	0.033	-9999	-0.37	2	2
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0	0	-9999	-10000	0	0
DUSP1	-0.12	0.29	-9999	-0.84	117	117
PAK1	-0.006	0.04	-9999	-0.28	18	18
SRC	0	0.01	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0.004	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	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	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.017	0.07	-9999	-0.36	14	14
BLK	-0.036	0.1	-9999	-0.3	102	102
HCK	-0.004	0.033	-9999	-10000	0	0
MAP2K3	0	0.01	-9999	-10000	0	0
DUSP16	0	0	-9999	-10000	0	0
DUSP10	-0.001	0.014	-9999	-10000	0	0
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.028	0.049	-9999	-0.41	2	2
positive regulation of innate immune response	0.023	0.075	-9999	-0.38	14	14
LCK	-0.019	0.1	-9999	-0.46	34	34
p38alpha-beta/MKP7	-0.012	0.056	-9999	-0.43	4	4
p38alpha-beta/MKP5	-0.012	0.056	-9999	-0.43	4	4
PGK/cGMP	-0.025	0.12	-9999	-0.65	32	32
PAK2	0	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.066	0.15	-9999	-0.4	119	119
CDC42	0	0	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
PAK3	-0.38	0.42	-9999	-0.84	377	377

×

BCR signaling pathway

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
JUN	0.004	0.12	-10000	0	-0.46	30	30
IKBKB	0.016	0.055	-10000	0	-0.25	3	3
AKT1	0.006	0.082	0.25	2	-0.28	15	17
IKBKG	0.018	0.057	-10000	0	-0.24	16	16
CALM1	-0.012	0.098	-10000	0	-0.46	26	26
PIK3CA	0	0.01	-10000	0	-10000	0	0
MAP3K1	-0.009	0.16	-10000	0	-0.67	28	28
MAP3K7	0	0.01	-10000	0	-0.28	1	1
mol:Ca2+	-0.021	0.1	-10000	0	-0.5	26	26
DOK1	0	0	-10000	0	-10000	0	0
AP-1	-0.049	0.12	-10000	0	-0.28	55	55
LYN	0	0	-10000	0	-10000	0	0
BLNK	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
BCR complex	-0.082	0.22	-10000	0	-0.7	87	87
CD22	-0.063	0.19	-10000	0	-0.57	80	80
CAMK2G	-0.004	0.092	-10000	0	-0.42	26	26
CSNK2A1	0	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.05	0.15	-10000	0	-0.82	14	14
GO:0007205	-0.022	0.1	-10000	0	-0.5	26	26
SYK	0	0.01	-10000	0	-10000	0	0
ELK1	-0.013	0.1	-10000	0	-0.47	26	26
NFATC1	-0.016	0.13	-10000	0	-0.56	28	28
B-cell antigen/BCR complex	-0.082	0.22	-10000	0	-0.7	87	87
PAG1/CSK	-0.001	0.013	-10000	0	-10000	0	0
NFKBIB	0.015	0.02	-10000	0	-10000	0	0
HRAS	-0.01	0.11	-10000	0	-0.49	26	26
NFKBIA	0.015	0.02	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.019	0.016	-10000	0	-10000	0	0
RasGAP/Csk	-0.061	0.17	-10000	0	-0.56	80	80
mol:GDP	-0.022	0.097	-10000	0	-0.47	26	26
PTEN	-0.002	0.041	-10000	0	-0.84	2	2
CD79B	-0.029	0.15	-10000	0	-0.84	26	26
NF-kappa-B/RelA/I kappa B alpha	0.019	0.016	-10000	0	-10000	0	0
GRB2	0	0.01	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.024	0.16	-10000	0	-0.48	78	78
PIK3R1	0	0	-10000	0	-10000	0	0
mol:IP3	-0.031	0.1	-10000	0	-0.51	26	26
CSK	0	0	-10000	0	-10000	0	0
FOS	-0.15	0.24	-10000	0	-0.47	289	289
CHUK	0.018	0.057	-10000	0	-0.24	16	16
IBTK	0	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.025	0.083	-10000	0	-0.48	16	16
PTPN6	-0.058	0.17	-10000	0	-0.77	32	32
RELA	0	0	-10000	0	-10000	0	0
BCL2A1	0.015	0.02	-10000	0	-0.13	1	1
VAV2	-0.07	0.18	-10000	0	-0.83	28	28
ubiquitin-dependent protein catabolic process	0.019	0.02	-10000	0	-10000	0	0
BTK	-0.004	0.006	-10000	0	-10000	0	0
CD19	-0.08	0.18	-10000	0	-0.57	78	78
MAP4K1	-0.01	0.062	-10000	0	-0.32	27	27
CD72	-0.006	0.048	-10000	0	-0.84	1	1
PAG1	-0.002	0.021	-10000	0	-0.28	5	5
MAPK14	0.002	0.13	-10000	0	-0.55	27	27
SH3BP5	0	0	-10000	0	-10000	0	0
PIK3AP1	-0.013	0.11	-10000	0	-0.55	26	26
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.044	0.14	-10000	0	-0.5	67	67
RAF1	-0.002	0.1	-10000	0	-0.45	26	26
RasGAP/p62DOK/SHIP	-0.058	0.17	-10000	0	-0.9	15	15
CD79A	-0.084	0.23	-10000	0	-0.84	66	66
re-entry into mitotic cell cycle	-0.048	0.12	-10000	0	-0.28	54	54
RASA1	0	0	-10000	0	-10000	0	0
MAPK3	0.015	0.087	-10000	0	-0.44	14	14
MAPK1	0.015	0.087	-10000	0	-0.44	14	14
CD72/SHP1	-0.055	0.16	-10000	0	-0.7	34	34
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	0.002	0.13	-10000	0	-0.55	27	27
actin cytoskeleton organization	-0.025	0.16	-10000	0	-0.67	28	28
NF-kappa-B/RelA	0.043	0.032	-10000	0	-10000	0	0
Calcineurin	-0.022	0.076	-10000	0	-0.46	14	14
PI3K	-0.055	0.13	-10000	0	-0.54	31	31
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.034	0.12	-10000	0	-0.59	26	26
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.055	0.18	-10000	0	-0.85	30	30
DAPP1	-0.054	0.21	-10000	0	-1	29	29
cytokine secretion	-0.014	0.12	-10000	0	-0.52	28	28
mol:DAG	-0.031	0.1	-10000	0	-0.51	26	26
PLCG2	-0.001	0.03	-10000	0	-0.56	2	2
MAP2K1	0.007	0.096	-10000	0	-0.5	14	14
B-cell antigen/BCR complex/FcgammaRIIB	-0.073	0.2	-10000	0	-0.65	80	80
mol:PI-3-4-5-P3	-0.04	0.093	0.35	2	-0.38	27	29
ETS1	0.004	0.089	-10000	0	-0.48	15	15
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.06	0.17	-10000	0	-0.56	78	78
B-cell antigen/BCR complex/LYN	-0.061	0.2	-10000	0	-0.6	78	78
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
RAC1	-0.028	0.17	-10000	0	-0.73	28	28
B-cell antigen/BCR complex/LYN/SYK	-0.059	0.19	-10000	0	-0.58	78	78
CARD11	-0.017	0.11	-10000	0	-0.49	27	27
FCGR2B	-0.003	0.051	-10000	0	-0.84	3	3
PPP3CA	0	0.01	-10000	0	-10000	0	0
BCL10	0	0	-10000	0	-10000	0	0
IKK complex	0.017	0.027	-10000	0	-10000	0	0
PTPRC	-0.007	0.06	-10000	0	-0.39	15	15
PDPK1	-0.026	0.063	0.23	2	-0.28	15	17
PPP3CB	0	0	-10000	0	-10000	0	0
PPP3CC	0	0	-10000	0	-10000	0	0
POU2F2	0.019	0.013	-10000	0	-10000	0	0

×

Insulin Pathway

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
CBL/APS/CAP	-0.12	0.22	-9999	-0.5	202	202
TC10/GTP	-0.1	0.18	-9999	-0.44	190	190
Insulin Receptor/Insulin/IRS1/Shp2	-0.02	0.1	-9999	-0.53	31	31
HRAS	0	0.01	-9999	-10000	0	0
APS homodimer	-0.01	0.051	-9999	-10000	0	0
GRB14	-0.1	0.23	-9999	-0.47	183	183
FOXO3	-0.013	0.065	-9999	-0.73	6	6
AKT1	-0.054	0.13	-9999	-0.54	6	6
INSR	0	0.009	-9999	-0.27	1	1
Insulin Receptor/Insulin	-0.003	0.028	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0	0	-9999	-10000	0	0
SORBS1	-0.19	0.35	-9999	-0.84	190	190
CRK	0	0	-9999	-10000	0	0
PTPN1	0.032	0.032	-9999	-10000	0	0
CAV1	-0.12	0.24	-9999	-0.54	187	187
CBL/APS/CAP/Crk-II/C3G	-0.11	0.2	-9999	-0.48	190	190
Insulin Receptor/Insulin/IRS1/NCK2	-0.02	0.1	-9999	-0.53	31	31
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.017	0.087	-9999	-0.46	31	31
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.012	0.055	-9999	-10000	0	0
RPS6KB1	-0.005	0.13	-9999	-0.48	6	6
PARD6A	-0.001	0.017	-9999	-0.28	3	3
CBL	0	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.001	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.047	0.11	-9999	-0.51	6	6
HRAS/GTP	-0.015	0.075	-9999	-0.49	1	1
Insulin Receptor	0	0.009	-9999	-0.27	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.018	0.093	-9999	-0.49	31	31
PRKCI	-0.012	0.032	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.059	0.14	-9999	-0.44	94	94
SHC1	0	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0.001	-9999	-10000	0	0
PI3K	-0.017	0.089	-9999	-0.47	31	31
NCK2	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
mol:H2O2	0	0.004	-9999	-10000	0	0
HRAS/GDP	0	0.006	-9999	-10000	0	0
AKT2	-0.054	0.13	-9999	-0.54	6	6
PRKCZ	-0.013	0.038	-9999	-0.63	1	1
SH2B2	-0.01	0.052	-9999	-10000	0	0
SHC/SHIP	-0.017	0.087	-9999	-0.46	31	31
F2RL2	-0.06	0.14	-9999	-0.84	14	14
TRIP10	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0.004	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0.005	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.12	0.22	-9999	-0.52	190	190
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0.004	-9999	-10000	0	0
INPP5D	-0.018	0.093	-9999	-0.5	31	31
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.008	0.071	-9999	-1	4	4
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.031	0.16	-9999	-0.84	31	31
p62DOK/RasGAP	0	0.001	-9999	-10000	0	0
INS	0.003	0.004	-9999	-10000	0	0
mol:PI-3-4-P2	-0.018	0.093	-9999	-0.49	31	31
GRB2	0	0.01	-9999	-10000	0	0
EIF4EBP1	-0.01	0.14	-9999	-0.48	10	10
PTPRA	0	0.001	-9999	-10000	0	0
PIK3CA	0	0.01	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.013	0.064	-9999	-0.34	31	31
Insulin Receptor/Insulin/IRS1	-0.02	0.1	-9999	-0.54	31	31
Insulin Receptor/Insulin/IRS3	-0.001	0.007	-9999	-10000	0	0
Par3/Par6	-0.025	0.072	-9999	-0.49	14	14

×

Arf6 trafficking 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
SLC2A4	-0.47	0.42	-10000	0	-0.84	476	476
CLTC	0.027	0.016	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.025	0.017	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.006	0.026	-10000	0	-10000	0	0
EXOC4	0	0	-10000	0	-10000	0	0
CD59	0.025	0.016	-10000	0	-0.28	1	1
CPE	0.006	0.083	-10000	0	-0.57	17	17
CTNNB1	0	0	-10000	0	-10000	0	0
membrane fusion	-0.001	0.016	-10000	0	-10000	0	0
CTNND1	-0.005	0.022	-10000	0	-10000	0	0
DNM2	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.03	0.012	-10000	0	-10000	0	0
TSHR	-0.009	0.12	-10000	0	-0.57	38	38
INS	0.011	0.004	-10000	0	-10000	0	0
BIN1	-0.009	0.087	-10000	0	-0.84	9	9
mol:Choline	-0.001	0.016	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.01	0.035	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.006	0.026	-10000	0	-10000	0	0
JUP	0.025	0.017	-10000	0	-0.28	1	1
ASAP2/amphiphysin II	-0.006	0.056	-10000	0	-0.52	10	10
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.017	0.052	-10000	0	-0.28	24	24
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	-0.004	0.034	-10000	0	-0.28	13	13
substrate adhesion-dependent cell spreading	0	0.001	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.008	0.033	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.018	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0	-10000	0	-10000	0	0
ACAP1	-0.001	0.017	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.02	0.014	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.032	0.02	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0	0	-10000	0	-10000	0	0
exocyst	0	0.001	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	-0.005	0.022	-10000	0	-10000	0	0
NME1	0.01	0.035	-10000	0	-10000	0	0
clathrin coat assembly	0.027	0.016	-10000	0	-10000	0	0
IL2RA	0.018	0.042	-10000	0	-0.33	10	10
VAMP3	0.018	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.24	0.21	-10000	0	-0.43	476	476
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	-0.002	0.027	-10000	0	-0.35	5	5
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0	0	-10000	0	-10000	0	0
PIP5K1C	0.03	0.012	-10000	0	-10000	0	0
SDC1	0.021	0.023	-10000	0	-0.36	1	1
ARF6/GDP	-0.007	0.031	-10000	0	-10000	0	0
EXOC7	0	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.009	0.034	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.001	0.016	-10000	0	-10000	0	0
endocytosis	0.006	0.056	0.51	10	-10000	0	10
SCAMP2	0	0	-10000	0	-10000	0	0
ADRB2	-0.091	0.22	-10000	0	-0.46	214	214
EXOC3	0	0	-10000	0	-10000	0	0
ASAP2	-0.001	0.029	-10000	0	-0.84	1	1
Dynamin 2/GDP	-0.006	0.026	-10000	0	-10000	0	0
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	-0.17	0.24	-10000	0	-0.46	351	351
RALA	0	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.007	0.029	-10000	0	-10000	0	0

×

Thromboxane A2 receptor signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.005	0.037	-10000	0	-0.28	15	15
GNB1/GNG2	-0.013	0.044	-10000	0	-0.19	43	43
AKT1	0.054	0.068	-10000	0	-0.2	43	43
EGF	-0.17	0.33	-10000	0	-0.84	167	167
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	-0.008	0.044	-10000	0	-0.34	2	2
mol:Ca2+	0.052	0.092	-10000	0	-0.3	43	43
LYN	-0.008	0.044	-10000	0	-0.34	2	2
RhoA/GTP	-0.007	0.028	-10000	0	-0.14	2	2
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.058	0.1	-10000	0	-0.34	43	43
GNG2	-0.006	0.071	-10000	0	-0.84	6	6
ARRB2	0	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.031	0.047	-10000	0	-0.6	3	3
G beta5/gamma2	-0.016	0.058	-10000	0	-0.25	43	43
PRKCH	0.054	0.1	-10000	0	-0.35	43	43
DNM1	-0.005	0.065	-10000	0	-0.74	6	6
TXA2/TP beta/beta Arrestin3	-0.004	0.026	-10000	0	-0.31	5	5
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.027	0.14	-10000	0	-0.84	25	25
G12 family/GTP	-0.018	0.068	-10000	0	-0.3	43	43
ADRBK1	0	0.01	-10000	0	-0.28	1	1
ADRBK2	-0.002	0.041	-10000	0	-0.84	2	2
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.041	0.072	0.36	12	-10000	0	12
mol:NADP	0	0	-10000	0	-10000	0	0
RAB11A	-0.001	0.014	-10000	0	-0.28	2	2
PRKG1	-0.032	0.16	-10000	0	-0.84	32	32
mol:IP3	0.054	0.11	-10000	0	-0.38	43	43
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	0.053	0.14	-10000	0	-0.51	43	43
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	0	0.06	-10000	0	-0.4	6	6
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.008	0.045	-10000	0	-0.34	2	2
RHOA	0	0	-10000	0	-10000	0	0
PTGIR	0	0.01	-10000	0	-0.28	1	1
PRKCB1	0.051	0.11	-10000	0	-0.37	43	43
GNAQ	-0.002	0.041	-10000	0	-0.84	2	2
mol:L-citrulline	0	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.055	0.15	-10000	0	-0.54	43	43
LCK	-0.011	0.07	-10000	0	-0.46	13	13
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.01	0.054	-10000	0	-0.31	25	25
TXA2-R family/G12 family/GDP/G beta/gamma	0.026	0.028	-10000	0	-0.3	2	2
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.009	0.053	-10000	0	-10000	0	0
MAPK14	0.055	0.074	-10000	0	-0.22	43	43
TGM2/GTP	0.054	0.12	-10000	0	-0.42	43	43
MAPK11	0.055	0.077	-10000	0	-0.23	43	43
ARHGEF1	0.041	0.058	-10000	0	-0.17	43	43
GNAI2	0	0	-10000	0	-10000	0	0
JNK cascade	0.055	0.12	-10000	0	-0.39	43	43
RAB11/GDP	-0.001	0.013	-10000	0	-0.28	2	2
ICAM1	0.051	0.087	-10000	0	-0.28	43	43
cAMP biosynthetic process	0.05	0.11	-10000	0	-0.35	43	43
Gq family/GTP/EBP50	-0.006	0.027	-10000	0	-0.25	9	9
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.008	0.044	-10000	0	-0.34	2	2
GNB5	0	0	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
EGF/EGFR	-0.026	0.1	-10000	0	-0.31	32	32
VCAM1	0.049	0.094	-10000	0	-0.31	43	43
TP beta/Gq family/GDP/G beta5/gamma2	0.031	0.047	-10000	0	-0.6	3	3
platelet activation	0.071	0.098	-10000	0	-0.3	43	43
PGI2/IP	0	0.006	-10000	0	-0.19	1	1
PRKACA	-0.012	0.066	-10000	0	-0.39	25	25
Gq family/GDP/G beta5/gamma2	0.029	0.049	-10000	0	-0.6	3	3
TXA2/TP beta/beta Arrestin2	-0.005	0.052	-10000	0	-0.67	5	5
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.011	0.061	-10000	0	-0.36	25	25
mol:DAG	0.053	0.12	-10000	0	-0.42	43	43
EGFR	-0.29	0.4	-10000	0	-0.83	297	297
TXA2/TP alpha	0.056	0.14	-10000	0	-0.48	43	43
Gq family/GTP	-0.003	0.031	-10000	0	-0.29	9	9
YES1	-0.009	0.046	-10000	0	-0.36	3	3
GNAI2/GTP	-0.009	0.051	-10000	0	-0.39	2	2
PGD2/DP	-0.021	0.11	-10000	0	-0.65	25	25
SLC9A3R1	-0.027	0.082	-10000	0	-10000	0	0
FYN	-0.009	0.046	-10000	0	-0.36	3	3
mol:NO	0	0	-10000	0	-10000	0	0
GNA15	-0.002	0.035	-10000	0	-0.39	5	5
PGK/cGMP	-0.022	0.11	-10000	0	-0.57	32	32
RhoA/GDP	0	0	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.011	0.068	-10000	0	-0.52	6	6
NOS3	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	0.047	0.12	-10000	0	-0.37	57	57
PRKCB	0.049	0.11	-10000	0	-0.36	53	53
PRKCE	0.055	0.1	-10000	0	-0.34	44	44
PRKCD	0.054	0.11	-10000	0	-0.37	43	43
PRKCG	0.05	0.11	-10000	0	-0.38	43	43
muscle contraction	0.058	0.14	-10000	0	-0.49	44	44
PRKCZ	0.058	0.1	-10000	0	-0.34	44	44
ARR3	-0.002	0.023	-10000	0	-0.28	6	6
TXA2/TP beta	-0.01	0.057	-10000	0	-0.34	10	10
PRKCQ	0.043	0.13	-10000	0	-0.37	66	66
MAPKKK cascade	0.052	0.13	-10000	0	-0.46	44	44
SELE	0.043	0.12	-10000	0	-0.42	43	43
TP beta/GNAI2/GDP/G beta/gamma	-0.012	0.067	-10000	0	-0.52	6	6
ROCK1	0	0	-10000	0	-10000	0	0
GNA14	-0.013	0.082	-10000	0	-0.4	27	27
chemotaxis	0.054	0.17	-10000	0	-0.62	43	43
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	0	0	-10000	0	-10000	0	0
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

TCGA08_retinoblastoma

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.002	0.057	-10000	0	-0.7	5	5
CDKN2C	0.006	0.032	-10000	0	-0.82	1	1
CDKN2A	-0.046	0.11	-10000	0	-0.29	133	133
CCND2	0.005	0.028	0.25	5	-0.17	6	11
RB1	-0.006	0.028	0.14	4	-0.26	5	9
CDK4	0.008	0.026	0.26	5	-10000	0	5
CDK6	0.006	0.032	0.28	5	-0.22	6	11
G1/S progression	-0.008	0.031	0.24	6	-0.17	2	8

×

IL2 signaling events mediated by STAT5

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
GAB2	-0.003	0.027	-9999	-0.28	8	8
ELF1	-0.011	0.047	-9999	-0.39	10	10
CCNA2	-0.12	0.14	-9999	-0.28	369	369
PIK3CA	0	0.01	-9999	-10000	0	0
JAK3	-0.004	0.033	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
JAK1	0	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.027	0.069	-9999	-0.61	4	4
SHC1	0	0	-9999	-10000	0	0
SP1	-0.003	0.033	-9999	-0.39	6	6
IL2RA	0.004	0.13	-9999	-1	10	10
IL2RB	-0.011	0.055	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
IL2RG	-0.016	0.083	-9999	-0.84	5	5
G1/S transition of mitotic cell cycle	0.012	0.1	-9999	-0.84	10	10
PTPN11	0	0	-9999	-10000	0	0
CCND2	0.021	0.091	-9999	-1	6	6
LCK	-0.019	0.1	-9999	-0.46	34	34
GRB2	0	0.01	-9999	-10000	0	0
IL2	-0.003	0.029	-9999	-10000	0	0
CDK6	-0.007	0.072	-9999	-0.84	6	6
CCND3	0.067	0.059	-9999	-0.63	2	2

×

Regulation of nuclear SMAD2/3 signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.002	0.01	-10000	0	-10000	0	0
HSPA8	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.1	0.21	-10000	0	-0.6	117	117
AKT1	0.013	0.005	-10000	0	-10000	0	0
GSC	-0.053	0.33	-10000	0	-1.5	39	39
NKX2-5	-0.038	0.095	-10000	0	-0.27	116	116
muscle cell differentiation	0.006	0.042	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1	0.002	0.029	-10000	0	-10000	0	0
SMAD4	0.012	0.033	-10000	0	-10000	0	0
CBFB	0	0	-10000	0	-10000	0	0
SAP18	0	0	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.23	0.27	-10000	0	-0.56	343	343
SMAD3/SMAD4/VDR	0.006	0.03	-10000	0	-0.49	1	1
MYC	-0.02	0.13	-10000	0	-0.84	20	20
CDKN2B	0.031	0.11	-10000	0	-1.5	4	4
AP1	-0.14	0.23	-10000	0	-0.57	58	58
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0	0.012	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.001	0.038	-10000	0	-0.35	1	1
SP3	0	0	-10000	0	-10000	0	0
CREB1	0	0	-10000	0	-10000	0	0
FOXH1	-0.04	0.093	-10000	0	-0.4	4	4
SMAD3/SMAD4/GR	-0.007	0.062	-10000	0	-0.63	7	7
GATA3	-0.039	0.16	-10000	0	-0.83	30	30
SKI/SIN3/HDAC complex/NCoR1	0.002	0.013	-10000	0	-10000	0	0
MEF2C/TIF2	-0.03	0.075	-10000	0	-0.65	5	5
endothelial cell migration	-0.01	0.035	-10000	0	-10000	0	0
MAX	0.001	0.004	-10000	0	-10000	0	0
RBBP7	-0.003	0.027	-10000	0	-10000	0	0
RBBP4	0	0	-10000	0	-10000	0	0
RUNX2	-0.004	0.033	-10000	0	-10000	0	0
RUNX3	-0.004	0.052	-10000	0	-0.84	3	3
RUNX1	-0.001	0.029	-10000	0	-0.84	1	1
CTBP1	0	0	-10000	0	-10000	0	0
NR3C1	-0.006	0.077	-10000	0	-0.84	7	7
VDR	0	0	-10000	0	-10000	0	0
CDKN1A	0.049	0.065	-10000	0	-1.4	1	1
KAT2B	0.001	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.014	0.069	-10000	0	-0.43	3	3
DCP1A	0	0	-10000	0	-10000	0	0
SKI	0	0	-10000	0	-10000	0	0
SERPINE1	0.01	0.035	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF2	-0.001	0.023	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.09	0.22	-10000	0	-0.6	126	126
SAP30	-0.001	0.017	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.006	0.024	-10000	0	-10000	0	0
JUN	-0.099	0.25	-10000	0	-0.58	50	50
SMAD3/SMAD4/IRF7	-0.011	0.058	-10000	0	-10000	0	0
TFE3	0.011	0.01	-10000	0	-10000	0	0
COL1A2	0.028	0.092	-10000	0	-1.2	1	1
mesenchymal cell differentiation	0.004	0.029	-10000	0	-10000	0	0
DLX1	-0.05	0.13	-10000	0	-0.84	8	8
TCF3	0	0	-10000	0	-10000	0	0
FOS	-0.26	0.4	-10000	0	-0.83	272	272
SMAD3/SMAD4/Max	-0.002	0.024	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0	0	-10000	0	-10000	0	0
ZBTB17	0	0.005	-10000	0	-10000	0	0
LAMC1	0.041	0.048	-10000	0	-0.82	1	1
TGIF2/HDAC complex/SMAD3/SMAD4	-0.001	0.023	-10000	0	-10000	0	0
IRF7	-0.019	0.071	-10000	0	-0.35	18	18
ESR1	-0.15	0.29	-10000	0	-0.57	227	227
HNF4A	-0.005	0.036	-10000	0	-0.28	14	14
MEF2C	0.001	0.086	-10000	0	-0.94	1	1
SMAD2-3/SMAD4	-0.003	0.03	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.003	0.025	-10000	0	-0.56	1	1
IGHV3OR16-13	0	0.008	-10000	0	-10000	0	0
TGIF2/HDAC complex	0	0	-10000	0	-10000	0	0
CREBBP	0.002	0.007	-10000	0	-10000	0	0
SKIL	-0.004	0.032	-10000	0	-10000	0	0
HDAC1	0	0	-10000	0	-10000	0	0
HDAC2	0	0	-10000	0	-10000	0	0
SNIP1	0	0	-10000	0	-10000	0	0
GCN5L2	0.001	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.002	0.026	-10000	0	-10000	0	0
MSG1/HSC70	-0.26	0.32	-10000	0	-0.64	343	343
SMAD2	0.014	0.022	-10000	0	-10000	0	0
SMAD3	0.012	0.03	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.005	0.021	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.028	0.021	-10000	0	-10000	0	0
NCOR1	-0.001	0.029	-10000	0	-0.84	1	1
NCOA2	-0.007	0.076	-10000	0	-0.84	7	7
NCOA1	-0.001	0.029	-10000	0	-0.84	1	1
MYOD/E2A	-0.002	0.018	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.006	0.031	-10000	0	-10000	0	0
IFNB1	0.016	0.083	-10000	0	-0.41	1	1
SMAD3/SMAD4/MEF2C	-0.021	0.068	-10000	0	-0.92	1	1
CITED1	-0.34	0.41	-10000	0	-0.82	352	352
SMAD2-3/SMAD4/ARC105	0	0.026	-10000	0	-10000	0	0
RBL1	-0.001	0.014	-10000	0	-0.28	2	2
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.007	0.05	-10000	0	-0.5	4	4
RUNX1-3/PEBPB2	-0.003	0.046	-10000	0	-0.73	3	3
SMAD7	-0.087	0.14	-10000	0	-0.57	8	8
MYC/MIZ-1	-0.015	0.1	-10000	0	-0.65	20	20
SMAD3/SMAD4	0.02	0.061	0.3	15	-10000	0	15
IL10	0.015	0.12	-10000	0	-0.57	24	24
PIASy/HDAC complex	0.001	0.003	-10000	0	-10000	0	0
PIAS3	0.001	0.005	-10000	0	-10000	0	0
CDK2	0.002	0.008	-10000	0	-10000	0	0
IL5	0.011	0.12	-10000	0	-0.54	30	30
CDK4	0.001	0.016	-10000	0	-10000	0	0
PIAS4	0.001	0.003	-10000	0	-10000	0	0
ATF3	-0.12	0.3	-10000	0	-0.84	126	126
SMAD3/SMAD4/SP1	0.001	0.025	-10000	0	-10000	0	0
FOXG1	-0.02	0.071	-10000	0	-0.28	59	59
FOXO3	0.025	0.033	-10000	0	-0.64	2	2
FOXO1	0.021	0.057	-10000	0	-0.64	6	6
FOXO4	0.026	0.007	-10000	0	-10000	0	0
heart looping	0.002	0.085	-10000	0	-0.92	1	1
CEBPB	0	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.027	0.081	-10000	0	-0.6	8	8
MYOD1	-0.003	0.029	-10000	0	-0.28	9	9
SMAD3/SMAD4/HNF4	-0.006	0.03	-10000	0	-10000	0	0
SMAD3/SMAD4/GATA3	-0.024	0.12	-10000	0	-0.6	30	30
SnoN/SIN3/HDAC complex/NCoR1	-0.004	0.032	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.001	0.048	-10000	0	-0.68	3	3
SMAD3/SMAD4/SP1-3	0.004	0.023	-10000	0	-10000	0	0
MED15	0	0	-10000	0	-10000	0	0
SP1	0.018	0.012	-10000	0	-10000	0	0
SIN3B	0	0	-10000	0	-10000	0	0
SIN3A	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.008	0.082	-10000	0	-0.46	3	3
ITGB5	0.05	0.043	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.067	0.19	-10000	0	-0.6	92	92
AR	-0.092	0.26	-10000	0	-0.83	93	93
negative regulation of cell growth	-0.027	0.076	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.006	0.03	-10000	0	-10000	0	0
E2F5	-0.006	0.041	-10000	0	-0.28	19	19
E2F4	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.002	0.05	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	0.001	0.04	-10000	0	-0.35	1	1
TFDP1	-0.001	0.019	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.14	0.23	-10000	0	-0.65	37	37
SMAD3/SMAD4/RUNX2	-0.004	0.029	-10000	0	-10000	0	0
TGIF2	0	0	-10000	0	-10000	0	0
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	0	0	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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
STX1A	0.003	0.038	-9999	-10000	0	0
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.048	0.14	-9999	-0.64	37	37
STXBP1	-0.004	0.058	-9999	-0.84	4	4
ACh/CHRNA1	-0.065	0.079	-9999	-0.27	9	9
RAB3GAP2/RIMS1/UNC13B	-0.04	0.12	-9999	-0.56	37	37
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	-0.068	0.19	-9999	-0.84	37	37
mol:ACh	0	0.033	-9999	-0.15	30	30
RAB3GAP2	0	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.039	0.099	-9999	-0.42	41	41
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.065	0.079	-9999	-0.27	9	9
UNC13B	0	0	-9999	-10000	0	0
CHRNA1	-0.1	0.14	-9999	-10000	0	0
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.059	0.13	-9999	-0.48	46	46
SNAP25	-0.017	0.072	-9999	-0.39	30	30
VAMP2	0	0	-9999	-10000	0	0
SYT1	-0.086	0.18	-9999	-0.36	199	199
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.008	0.048	-9999	-0.57	4	4
STX1A/SNAP25 fragment 1/VAMP2	-0.039	0.099	-9999	-0.42	41	41

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.051	0.11	-9999	-0.65	3	3
RAD9A	0	0.01	-9999	-10000	0	0
AP1	-0.21	0.31	-9999	-0.66	273	273
IFNAR2	0.009	0.006	-9999	-10000	0	0
AKT1	-0.037	0.11	-9999	-0.3	79	79
ER alpha/Oestrogen	-0.12	0.22	-9999	-0.65	117	117
NFX1/SIN3/HDAC complex	0	0.001	-9999	-10000	0	0
EGF	-0.17	0.33	-9999	-0.84	167	167
SMG5	0	0	-9999	-10000	0	0
SMG6	0	0	-9999	-10000	0	0
SP3/HDAC2	0	0	-9999	-10000	0	0
TERT/c-Abl	-0.064	0.085	-9999	-0.6	3	3
SAP18	0	0	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.15	0.14	-9999	-0.29	3	3
WRN	0	0	-9999	-10000	0	0
SP1	0.01	0.006	-9999	-10000	0	0
SP3	0	0	-9999	-10000	0	0
TERF2IP	0	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.049	0.074	-9999	-0.54	3	3
Mad/Max	0	0.006	-9999	-10000	0	0
TERT	-0.051	0.12	-9999	-0.66	3	3
CCND1	-0.044	0.13	-9999	-1.3	3	3
MAX	0	0	-9999	-10000	0	0
RBBP7	-0.003	0.027	-9999	-10000	0	0
RBBP4	0	0	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
Telomerase/911	-0.001	0.005	-9999	-10000	0	0
CDKN1B	0.006	0.079	-9999	-0.91	3	3
RAD1	0	0	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
SAP30	-0.001	0.017	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0	0	-9999	-10000	0	0
JUN	-0.009	0.086	-9999	-0.84	9	9
E6	0	0.001	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0	-9999	-10000	0	0
FOS	-0.27	0.39	-9999	-0.84	272	272
IFN-gamma/IRF1	-0.025	0.062	-9999	-0.36	4	4
PARP2	0	0	-9999	-10000	0	0
BLM	-0.032	0.089	-9999	-0.28	98	98
Telomerase	-0.003	0.025	-9999	-10000	0	0
IRF1	-0.001	0.018	-9999	-10000	0	0
ESR1	-0.15	0.29	-9999	-0.56	228	228
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0.002	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0	0.002	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC2	0.009	0.006	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.022	0.002	-9999	-10000	0	0
ABL1	0	0	-9999	-10000	0	0
MXD1	0	0.01	-9999	-10000	0	0
MRE11A	0	0	-9999	-10000	0	0
HUS1	0	0	-9999	-10000	0	0
RPS6KB1	-0.001	0.014	-9999	-0.28	2	2
TERT/NF kappa B1/14-3-3	-0.062	0.098	-9999	-0.67	3	3
NR2F2	-0.001	0.05	-9999	-0.84	3	3
MAPK3	0.014	0.021	-9999	-10000	0	0
MAPK1	0.014	0.021	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0	0.001	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
HNRNPC	0	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	0	-9999	-10000	0	0
EGFR	-0.29	0.4	-9999	-0.83	297	297
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.35	0.37	-9999	-0.71	410	410
MYC	-0.02	0.13	-9999	-0.84	20	20
IL2	0.003	0.03	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0	0	-9999	-10000	0	0
HSP90AA1	0	0.01	-9999	-0.28	1	1
TGFB1	0	0.001	-9999	-10000	0	0
TRF2/BLM	-0.018	0.05	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.059	0.083	-9999	-0.6	3	3
SP1/HDAC2	0	0	-9999	-10000	0	0
PINX1	0	0	-9999	-10000	0	0
Telomerase/EST1A	-0.049	0.074	-9999	-0.54	3	3
Smad3/Myc	-0.013	0.085	-9999	-0.56	20	20
911 complex	0	0.005	-9999	-10000	0	0
IFNG	-0.039	0.096	-9999	-0.27	15	15
Telomerase/PinX1	-0.049	0.074	-9999	-0.54	3	3
Telomerase/AKT1/mTOR/p70S6K	0.004	0.054	-9999	-10000	0	0
SIN3B	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
Telomerase/EST1B	-0.049	0.074	-9999	-0.54	3	3
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.049	0.074	-9999	-0.54	3	3
E2F1	-0.088	0.14	-9999	-10000	0	0
ZNFX1	0	0	-9999	-10000	0	0
PIF1	-0.052	0.11	-9999	-10000	0	0
NCL	0	0	-9999	-10000	0	0
DKC1	-0.001	0.014	-9999	-0.28	2	2
telomeric DNA binding	0	0	-9999	-10000	0	0

×

TCGA08_p53

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.02	0.072	-9999	-0.19	133	133
TP53	-0.007	0.018	-9999	-10000	0	0
Senescence	-0.007	0.018	-9999	-10000	0	0
Apoptosis	-0.007	0.018	-9999	-10000	0	0
Activated_Oncogenes	0	0	-9999	-10000	0	0
MDM2	0.014	0.037	-9999	-10000	0	0
MDM4	0	0	-9999	-10000	0	0

×

Syndecan-2-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
Syndecan-2/Fibronectin	-0.064	0.075	-9999	-0.42	6	6
EPHB2	-0.005	0.037	-9999	-0.28	15	15
Syndecan-2/TACI	-0.017	0.081	-9999	-0.56	16	16
LAMA1	-0.095	0.26	-9999	-0.83	97	97
Syndecan-2/alpha2 ITGB1	-0.12	0.22	-9999	-0.49	213	213
HRAS	0	0.01	-9999	-10000	0	0
Syndecan-2/CASK	-0.003	0.035	-9999	-0.56	3	3
ITGA5	0	0	-9999	-10000	0	0
BAX	0.038	0.033	-9999	-0.49	3	3
EPB41	0	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.002	0.032	-9999	-0.51	3	3
LAMA3	-0.2	0.36	-9999	-0.84	201	201
EZR	-0.001	0.014	-9999	-0.28	2	2
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.11	0.28	-9999	-0.84	106	106
Syndecan-2/MMP2	-0.008	0.077	-9999	-0.75	8	8
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.012	0.088	-9999	-0.64	16	16
dendrite morphogenesis	-0.005	0.039	-9999	-0.55	3	3
Syndecan-2/GM-CSF	-0.005	0.039	-9999	-0.56	3	3
determination of left/right symmetry	0.016	0.042	-9999	-0.64	3	3
Syndecan-2/PKC delta	-0.003	0.035	-9999	-0.56	3	3
GNB2L1	0	0	-9999	-10000	0	0
MAPK3	0.022	0.039	-9999	-0.51	3	3
MAPK1	0.022	0.039	-9999	-0.51	3	3
Syndecan-2/RACK1	-0.002	0.03	-9999	-0.48	3	3
NF1	-0.001	0.029	-9999	-0.84	1	1
FGFR/FGF/Syndecan-2	0.016	0.042	-9999	-0.64	3	3
ITGA2	-0.016	0.11	-9999	-0.84	16	16
MAPK8	0.032	0.037	-9999	-0.55	3	3
Syndecan-2/alpha2/beta1 Integrin	-0.065	0.19	-9999	-0.55	99	99
Syndecan-2/Kininogen	-0.005	0.038	-9999	-0.56	3	3
ITGB1	0	0	-9999	-10000	0	0
SRC	-0.002	0.028	-9999	-0.45	3	3
Syndecan-2/CASK/Protein 4.1	-0.002	0.032	-9999	-0.52	3	3
extracellular matrix organization	-0.003	0.034	-9999	-0.55	3	3
actin cytoskeleton reorganization	-0.063	0.075	-9999	-0.42	6	6
Syndecan-2/Caveolin-2/Ras	-0.067	0.18	-9999	-0.52	106	106
Syndecan-2/Laminin alpha3	-0.14	0.24	-9999	-0.56	204	204
Syndecan-2/RasGAP	-0.002	0.028	-9999	-0.46	3	3
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
PRKCD	0	0.01	-9999	-10000	0	0
Syndecan-2 dimer	-0.005	0.039	-9999	-0.56	3	3
GO:0007205	0	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.002	0.027	-9999	-0.44	3	3
RHOA	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
TNFRSF13B	-0.024	0.12	-9999	-0.84	13	13
RASA1	0	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.012	0.088	-9999	-0.64	16	16
Syndecan-2/Synbindin	-0.003	0.034	-9999	-0.56	3	3
TGFB1	0	0	-9999	-10000	0	0
CASP3	0.029	0.034	-9999	-0.5	3	3
FN1	-0.12	0.14	-9999	-10000	0	0
Syndecan-2/IL8	-0.023	0.091	-9999	-0.56	20	20
SDC2	0.016	0.042	-9999	-0.64	3	3
KNG1	-0.004	0.033	-9999	-10000	0	0
Syndecan-2/Neurofibromin	-0.003	0.039	-9999	-0.56	4	4
TRAPPC4	0	0	-9999	-10000	0	0
CSF2	-0.005	0.038	-9999	-10000	0	0
Syndecan-2/TGFB1	-0.003	0.034	-9999	-0.56	3	3
Syndecan-2/Syntenin/PI-4-5-P2	-0.002	0.032	-9999	-0.52	3	3
Syndecan-2/Ezrin	-0.003	0.032	-9999	-0.51	3	3
PRKACA	0.029	0.038	-9999	-0.5	4	4
angiogenesis	-0.023	0.091	-9999	-0.56	20	20
MMP2	-0.008	0.081	-9999	-0.84	8	8
IL8	-0.036	0.14	-9999	-0.84	17	17
calcineurin-NFAT signaling pathway	-0.016	0.08	-9999	-0.56	16	16

×

Ceramide signaling pathway

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.021	0.023	-10000	0	-0.64	1	1
MAP4K4	-0.005	0.034	-10000	0	-10000	0	0
BAG4	-0.003	0.03	-10000	0	-0.28	10	10
PKC zeta/ceramide	-0.025	0.05	-10000	0	-0.61	1	1
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.082	-10000	0	-0.84	7	7
BAX	-0.009	0.022	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
AKT1	0.024	0.01	-10000	0	-10000	0	0
BAD	-0.023	0.047	0.21	1	-10000	0	1
SMPD1	0.025	0.032	-10000	0	-0.25	10	10
RB1	-0.024	0.05	0.21	1	-0.51	1	2
FADD/Caspase 8	-0.005	0.035	-10000	0	-0.34	2	2
MAP2K4	-0.015	0.047	-10000	0	-0.49	1	1
NSMAF	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.015	0.048	-10000	0	-0.48	1	1
EGF	-0.17	0.33	-10000	0	-0.84	167	167
mol:ceramide	-0.034	0.05	0.22	1	-0.13	148	149
MADD	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.021	0.026	-10000	0	-0.64	1	1
ASAH1	-0.001	0.017	-10000	0	-0.28	3	3
negative regulation of cell cycle	-0.023	0.05	0.21	1	-0.5	1	2
cell proliferation	-0.1	0.17	-10000	0	-0.41	186	186
BID	0.023	0.033	-10000	0	-10000	0	0
MAP3K1	-0.023	0.047	0.21	1	-10000	0	1
EIF2A	-0.006	0.043	-10000	0	-10000	0	0
TRADD	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
MAPK3	-0.003	0.046	-10000	0	-0.44	1	1
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.003	0.046	-10000	0	-0.44	1	1
Cathepsin D/ceramide	-0.029	0.05	-10000	0	-10000	0	0
FADD	-0.007	0.038	-10000	0	-0.37	2	2
KSR1	-0.024	0.051	0.21	1	-0.34	3	4
MAPK8	-0.011	0.046	0.2	1	-0.32	2	3
PRKRA	-0.023	0.047	0.21	1	-10000	0	1
PDGFA	-0.001	0.029	-10000	0	-0.84	1	1
TRAF2	0	0	-10000	0	-10000	0	0
IGF1	-0.18	0.35	-10000	0	-0.84	186	186
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.034	0.05	0.22	1	-0.13	148	149
CTSD	-0.01	0.052	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.11	0.18	-10000	0	-0.44	186	186
PRKCD	0	0.01	-10000	0	-10000	0	0
PRKCZ	-0.001	0.029	-10000	0	-0.84	1	1
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.021	0.026	-10000	0	-0.64	1	1
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.005	0.037	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.011	0.065	-10000	0	-0.56	10	10
mol:Sphingosine-1-phosphate	0.021	0.023	-10000	0	-0.64	1	1
MAP2K1	-0.007	0.046	-10000	0	-0.45	1	1
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
CYCS	-0.009	0.044	0.19	18	-10000	0	18
TNFRSF1A	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.002	0.019	-10000	0	-10000	0	0
EIF2AK2	-0.014	0.044	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.009	0.063	-10000	0	-0.56	10	10
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.002	0.02	-10000	0	-10000	0	0
MAP2K2	-0.007	0.046	-10000	0	-0.45	1	1
SMPD3	0.026	0.039	-10000	0	-0.27	12	12
TNF	-0.016	0.098	-10000	0	-0.84	10	10
PKC zeta/PAR4	-0.001	0.022	-10000	0	-0.64	1	1
mol:PHOSPHOCHOLINE	0.047	0.12	0.28	168	-10000	0	168
NF kappa B1/RelA/I kappa B alpha	-0.001	0.016	-10000	0	-0.47	1	1
AIFM1	-0.009	0.044	0.19	18	-10000	0	18
BCL2	-0.024	0.14	-10000	0	-0.84	24	24

×

E-cadherin signaling events

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
E-cadherin/beta catenin-gamma catenin	-0.017	0.095	-9999	-0.56	25	25
E-cadherin/beta catenin	-0.018	0.11	-9999	-0.64	24	24
CTNNB1	0	0	-9999	-10000	0	0
JUP	-0.002	0.032	-9999	-0.46	3	3
CDH1	-0.024	0.14	-9999	-0.84	24	24

×

Osteopontin-mediated events

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
IKK alpha homodimer	-0.03	0.068	-9999	-0.47	14	14
NF kappa B1 p50/RelA/I kappa B alpha	-0.017	0.054	-9999	-0.49	2	2
alphaV/beta3 Integrin/Osteopontin/Src	-0.046	0.073	-9999	-10000	0	0
AP1	-0.16	0.22	-9999	-0.79	24	24
ILK	-0.01	0.088	-9999	-0.5	14	14
bone resorption	-0.022	0.063	-9999	-0.7	2	2
PTK2B	0	0	-9999	-10000	0	0
PYK2/p130Cas	0.014	0.076	-9999	-0.52	3	3
ITGAV	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.002	0.033	-9999	-0.64	2	2
alphaV/beta3 Integrin/Osteopontin	-0.042	0.086	-9999	-0.56	14	14
MAP3K1	-0.035	0.075	-9999	-0.51	14	14
JUN	-0.009	0.086	-9999	-0.84	9	9
MAPK3	0.015	0.089	-9999	-0.46	14	14
MAPK1	0.015	0.089	-9999	-0.46	14	14
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0.012	0.088	-9999	-0.47	14	14
ITGB3	-0.015	0.11	-9999	-0.83	14	14
NFKBIA	0.028	0.086	-9999	-0.45	14	14
FOS	-0.27	0.39	-9999	-0.84	272	272
CD44	-0.001	0.017	-9999	-0.28	3	3
CHUK	0	0	-9999	-10000	0	0
PLAU	0.025	0.087	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.016	0.052	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.011	0.082	-9999	-0.63	14	14
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.035	0.076	-9999	-0.51	14	14
VAV3	0.005	0.095	-9999	-0.48	17	17
MAP3K14	0.002	0.094	-9999	-0.5	14	14
ROCK2	-0.002	0.041	-9999	-0.84	2	2
SPP1	-0.077	0.12	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.028	0.067	-9999	-0.5	4	4
MMP2	-0.13	0.18	-9999	-0.7	24	24

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.001	0.003	-9999	-10000	0	0
HDAC2	0.001	0.003	-9999	-10000	0	0
GNB1/GNG2	-0.009	0.073	-9999	-0.6	12	12
forebrain development	-0.026	0.2	-9999	-0.53	101	101
GNAO1	-0.033	0.14	-9999	-0.84	21	21
SMO/beta Arrestin2	-0.006	0.059	-9999	-0.65	7	7
SMO	-0.005	0.077	-9999	-0.84	7	7
ARRB2	0	0.001	-9999	-10000	0	0
GLI3/SPOP	-0.003	0.038	-9999	-10000	0	0
mol:GTP	0	0.003	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0	0.007	-9999	-10000	0	0
GNAI1	-0.043	0.18	-9999	-0.84	43	43
XPO1	0.011	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.053	0.16	-9999	-0.53	57	57
SAP30	0	0.017	-9999	-10000	0	0
mol:GDP	-0.005	0.077	-9999	-0.84	7	7
MIM/GLI2A	0.001	0.03	-9999	-0.28	9	9
IFT88	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GLI2	0.041	0.032	-9999	-10000	0	0
GLI3	0.038	0.043	-9999	-0.31	11	11
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
SAP18	0.001	0.003	-9999	-10000	0	0
embryonic digit morphogenesis	0	0	-9999	-10000	0	0
GNG2	-0.006	0.07	-9999	-0.84	6	6
Gi family/GTP	-0.031	0.095	-9999	-0.38	37	37
SIN3B	0.001	0.003	-9999	-10000	0	0
SIN3A	0.001	0.003	-9999	-10000	0	0
GLI3/Su(fu)	-0.002	0.024	-9999	-10000	0	0
GLI2/Su(fu)	-0.004	0.035	-9999	-0.41	4	4
FOXA2	-0.013	0.033	-9999	-10000	0	0
neural tube patterning	-0.026	0.2	-9999	-0.53	101	101
SPOP	0	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.002	0.023	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
CSNK1G3	0	0	-9999	-10000	0	0
MTSS1	0.001	0.03	-9999	-0.28	9	9
embryonic limb morphogenesis	-0.026	0.2	-9999	-0.53	101	101
SUFU	-0.002	0.027	-9999	-0.31	1	1
LGALS3	-0.009	0.086	-9999	-0.84	9	9
catabolic process	-0.004	0.029	-9999	-10000	0	0
GLI3A/CBP	-0.027	0.099	-9999	-0.39	59	59
KIF3A	0	0	-9999	-10000	0	0
GLI1	-0.027	0.21	-9999	-0.54	101	101
RAB23	0	0	-9999	-10000	0	0
CSNK1A1	0	0	-9999	-10000	0	0
IFT172	-0.001	0.029	-9999	-0.84	1	1
RBBP7	-0.002	0.027	-9999	-10000	0	0
Su(fu)/Galectin3	-0.008	0.063	-9999	-0.57	9	9
GNAZ	-0.006	0.07	-9999	-0.84	6	6
RBBP4	0.001	0.003	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GLI2/SPOP	-0.003	0.024	-9999	-10000	0	0
STK36	0.011	0.005	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.027	0.095	-9999	-0.55	10	10
PTCH1	-0.062	0.34	-9999	-1.2	64	64
MIM/GLI1	-0.053	0.19	-9999	-0.5	101	101
CREBBP	-0.027	0.099	-9999	-0.39	59	59
Su(fu)/SIN3/HDAC complex	0.006	0.019	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.022	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0.007	-10000	0	-10000	0	0
CDKN1B	0.035	0.03	-10000	0	-0.46	3	3
CDKN1A	0.036	0.018	-10000	0	-0.46	1	1
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	-0.001	0.019	-10000	0	-0.28	4	4
FOXO3	0.036	0.024	-10000	0	-0.46	2	2
AKT1	0	0.001	-10000	0	-10000	0	0
BAD	0	0	-10000	0	-10000	0	0
AKT3	-0.006	0.052	-10000	0	-0.46	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.037	0.002	-10000	0	-10000	0	0
AKT1/ASK1	-0.001	0.022	-10000	0	-0.44	2	2
BAD/YWHAZ	0	0.008	-10000	0	-10000	0	0
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	0	0	-10000	0	-10000	0	0
JNK cascade	0.001	0.021	0.43	2	-10000	0	2
TSC1	0.037	0.002	-10000	0	-10000	0	0
YWHAZ	-0.001	0.017	-10000	0	-0.28	3	3
AKT1/RAF1	0	0.001	-10000	0	-10000	0	0
EP300	0	0	-10000	0	-10000	0	0
mol:GDP	0	0.001	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.037	0.002	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
TBC1D4	0.024	0.02	-10000	0	-0.55	1	1
MAP3K5	-0.002	0.041	-10000	0	-0.84	2	2
MAPKAP1	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.039	0.024	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
AKT1S1	0.037	0.002	-10000	0	-10000	0	0
CASP9	0.037	0.002	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	-0.001	0.026	-10000	0	-0.43	3	3
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0	0.007	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
SRC	0	0.01	-10000	0	-10000	0	0
AKT2/p21CIP1	-0.001	0.015	-10000	0	-0.44	1	1
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.017	0.001	-10000	0	-10000	0	0
CHUK	0.037	0.002	-10000	0	-10000	0	0
BAD/BCL-XL	0	0.002	-10000	0	-10000	0	0
mTORC2	0	0	-10000	0	-10000	0	0
AKT2	0	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.053	0.031	-10000	0	-10000	0	0
PDPK1	0	0	-10000	0	-10000	0	0
MDM2	0.036	0.009	-10000	0	-10000	0	0
MAPKKK cascade	0	0.001	-10000	0	-10000	0	0
MDM2/Cbp/p300	0	0.005	-10000	0	-10000	0	0
TSC1/TSC2	0.043	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0.005	-10000	0	-10000	0	0
glucose import	-0.27	0.27	-10000	0	-0.5	476	476
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.031	0.002	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.28	0.27	-10000	0	-0.51	476	476
GSK3A	0.037	0.002	-10000	0	-10000	0	0
FOXO1	0.033	0.042	-10000	0	-0.46	6	6
GSK3B	0.037	0.002	-10000	0	-10000	0	0
SFN	-0.016	0.11	-10000	0	-0.62	21	21
G1/S transition of mitotic cell cycle	0.044	0.002	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.041	0.035	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
KPNA1	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0.01	-10000	0	-0.28	1	1
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.007	0.077	-10000	0	-0.84	7	7
positive regulation of NF-kappaB transcription factor activity	-0.067	0.2	-10000	0	-0.64	87	87
MAP2K4	-0.004	0.033	-10000	0	-0.46	1	1
IKBKB	-0.001	0.014	-10000	0	-0.28	2	2
TNFRSF10B	0	0	-10000	0	-10000	0	0
TNFRSF10A	-0.004	0.058	-10000	0	-0.84	4	4
SMPD1	-0.003	0.027	-10000	0	-0.3	7	7
IKBKG	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.08	0.25	-10000	0	-0.84	80	80
TRAIL/TRAILR2	-0.006	0.059	-10000	0	-0.64	7	7
TRAIL/TRAILR3	-0.009	0.076	-10000	0	-0.7	9	9
TRAIL/TRAILR1	-0.009	0.074	-10000	0	-0.64	11	11
TRAIL/TRAILR4	-0.067	0.2	-10000	0	-0.64	87	87
TRAIL/TRAILR1/DAP3/GTP	-0.007	0.059	-10000	0	-0.52	11	11
IKK complex	-0.003	0.02	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0.006	-10000	0	-10000	0	0
MAPK3	0.016	0.061	-10000	0	-0.64	7	7
MAP3K1	-0.004	0.032	-10000	0	-0.33	7	7
TRAILR4 (trimer)	-0.08	0.24	-10000	0	-0.84	80	80
TRADD	0	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	-0.004	0.058	-10000	0	-0.84	4	4
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.005	0.039	-10000	0	-0.34	11	11
CFLAR	0	0	-10000	0	-10000	0	0
MAPK1	0.016	0.061	-10000	0	-0.64	7	7
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.008	0.057	-10000	0	-0.49	11	11
mol:ceramide	-0.003	0.027	-10000	0	-0.3	7	7
FADD	-0.005	0.038	-10000	0	-0.28	16	16
MAPK8	0.048	0.037	-10000	0	-0.43	1	1
TRAF2	0	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.006	0.057	-10000	0	-0.84	3	3
CHUK	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.01	0.067	-10000	0	-0.57	11	11
DAP3	0	0.01	-10000	0	-0.28	1	1
CASP10	0.021	0.11	0.31	76	-0.53	10	86
JNK cascade	-0.067	0.2	-10000	0	-0.64	87	87
TRAIL (trimer)	-0.007	0.077	-10000	0	-0.84	7	7
TNFRSF10C	-0.006	0.057	-10000	0	-0.84	3	3
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.009	0.058	-10000	0	-0.49	11	11
TRAIL/TRAILR2/FADD	-0.007	0.054	-10000	0	-0.56	7	7
cell death	-0.003	0.027	-10000	0	-0.3	7	7
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.003	0.031	-10000	0	-0.34	7	7
TRAILR2 (trimer)	0	0	-10000	0	-10000	0	0
CASP8	0.001	0.015	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.006	0.045	-10000	0	-0.48	7	7

×

Caspase cascade in apoptosis

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.005	0.096	-10000	0	-0.46	29	29
ACTA1	-0.018	0.14	-10000	0	-0.64	30	30
NUMA1	0.005	0.096	-10000	0	-0.46	29	29
SPTAN1	-0.005	0.13	-10000	0	-0.65	26	26
LIMK1	-0.005	0.13	-10000	0	-0.65	26	26
BIRC3	-0.01	0.082	-10000	0	-0.84	7	7
BIRC2	0	0	-10000	0	-10000	0	0
BAX	0	0	-10000	0	-10000	0	0
CASP10	-0.016	0.15	-10000	0	-0.69	30	30
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.005	0.096	-10000	0	-0.46	29	29
DIABLO	0	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.004	0.13	-10000	0	-0.63	26	26
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
GSN	-0.012	0.15	-10000	0	-0.66	35	35
MADD	0	0	-10000	0	-10000	0	0
TFAP2A	0.014	0.08	-10000	0	-0.67	11	11
BID	0.005	0.064	-10000	0	-0.3	29	29
MAP3K1	0.004	0.04	-10000	0	-0.24	6	6
TRADD	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.005	0.13	-10000	0	-0.65	26	26
CASP9	0	0.002	-10000	0	-10000	0	0
DNA repair	-0.002	0.031	0.19	1	-0.22	3	4
neuron apoptosis	0.021	0.013	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.002	0.12	-10000	0	-0.62	26	26
APAF1	0	0	-10000	0	-10000	0	0
CASP6	0.022	0.056	-10000	0	-0.36	3	3
TRAF2	0	0	-10000	0	-10000	0	0
ICAD/CAD	0.003	0.13	-10000	0	-0.62	26	26
CASP7	-0.007	0.037	0.36	7	-10000	0	7
KRT18	0.015	0.017	-10000	0	-10000	0	0
apoptosis	0.008	0.11	-10000	0	-0.55	26	26
DFFA	-0.005	0.13	-10000	0	-0.65	26	26
DFFB	-0.005	0.13	-10000	0	-0.65	26	26
PARP1	0.002	0.031	0.22	3	-0.19	1	4
actin filament polymerization	-0.003	0.12	0.6	26	-10000	0	26
TNF	-0.016	0.098	-10000	0	-0.84	10	10
CYCS	0.007	0.051	-10000	0	-0.22	29	29
SATB1	0.019	0.095	-10000	0	-0.5	19	19
SLK	-0.005	0.13	-10000	0	-0.65	26	26
p15 BID/BAX	-0.013	0.05	-10000	0	-0.35	6	6
CASP2	0.043	0.039	-10000	0	-10000	0	0
JNK cascade	-0.004	0.039	0.24	6	-10000	0	6
CASP3	-0.014	0.14	-10000	0	-0.65	30	30
LMNB2	0.04	0.035	-10000	0	-0.26	2	2
RIPK1	0	0	-10000	0	-10000	0	0
CASP4	-0.001	0.029	-10000	0	-0.84	1	1
Mammalian IAPs/DIABLO	-0.006	0.048	-10000	0	-0.51	7	7
negative regulation of DNA binding	0.014	0.079	-10000	0	-0.66	11	11
stress fiber formation	-0.004	0.13	-10000	0	-0.63	26	26
GZMB	-0.029	0.16	-10000	0	-0.66	38	38
CASP1	-0.002	0.027	-10000	0	-0.46	3	3
LMNB1	0.045	0.036	-10000	0	-0.28	1	1
APP	0.021	0.013	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.011	0	-10000	0	-10000	0	0
VIM	0.003	0.11	-10000	0	-0.54	26	26
LMNA	0.04	0.035	-10000	0	-0.28	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.005	0.034	-10000	0	-10000	0	0
LRDD	0	0.01	-10000	0	-10000	0	0
SREBF1	-0.007	0.13	-10000	0	-0.66	26	26
APAF-1/Caspase 9	-0.004	0.02	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.005	0.094	-10000	0	-0.45	29	29
CFL2	0.003	0.13	-10000	0	-0.62	26	26
GAS2	-0.054	0.2	-10000	0	-0.54	103	103
positive regulation of apoptosis	0.046	0.035	-10000	0	-0.28	1	1
PRF1	-0.02	0.12	-10000	0	-0.84	17	17

×

Cellular roles of Anthrax toxin

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0	0.01	-10000	0	-0.28	1	1
ANTXR2	-0.009	0.086	-10000	0	-0.84	9	9
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.001	0.011	-10000	0	-0.1	9	9
monocyte activation	0.006	0.065	-10000	0	-0.46	16	16
MAP2K2	0	0.005	-10000	0	-10000	0	0
MAP2K1	-0.001	0.009	-10000	0	-10000	0	0
MAP2K7	-0.001	0.009	-10000	0	-10000	0	0
MAP2K6	-0.012	0.074	-10000	0	-0.51	18	18
CYAA	-0.005	0.051	-10000	0	-0.5	9	9
MAP2K4	-0.002	0.02	-10000	0	-0.5	1	1
IL1B	0.009	0.06	-10000	0	-0.35	20	20
Channel	-0.006	0.054	-10000	0	-0.52	9	9
NLRP1	-0.008	0.06	-10000	0	-0.52	11	11
CALM1	0	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.001	0.013	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.001	0.011	0.1	9	-10000	0	9
MAPK3	-0.001	0.009	-10000	0	-10000	0	0
MAPK1	-0.001	0.009	-10000	0	-10000	0	0
PGR	-0.15	0.22	-10000	0	-0.5	230	230
PA/Cellular Receptors	-0.006	0.059	-10000	0	-0.57	9	9
apoptosis	-0.001	0.011	-10000	0	-0.1	9	9
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.005	0.051	-10000	0	-0.49	9	9
macrophage activation	0.02	0.01	-10000	0	-10000	0	0
TNF	-0.016	0.098	-10000	0	-0.84	10	10
VCAM1	-0.009	0.064	-10000	0	-0.46	16	16
platelet activation	-0.001	0.013	-10000	0	-10000	0	0
MAPKKK cascade	-0.013	0.023	0.11	18	-10000	0	18
IL18	0.011	0.036	-10000	0	-0.22	11	11
negative regulation of macrophage activation	-0.001	0.011	-10000	0	-0.1	9	9
LEF	-0.001	0.011	-10000	0	-0.1	9	9
CASP1	-0.004	0.029	-10000	0	-0.25	11	11
mol:cAMP	-0.001	0.013	-10000	0	-10000	0	0
necrosis	-0.001	0.011	-10000	0	-0.1	9	9
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.005	0.051	-10000	0	-0.5	9	9
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.03	0.01	-9999	-10000	0	0
SNTA1	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.017	0.045	-9999	-10000	0	0
MAPK12	0.017	0.086	-9999	-0.51	21	21
CCND1	0.015	0.043	-9999	-0.23	20	20
p38 gamma/SNTA1	-0.012	0.076	-9999	-0.5	18	18
MAP2K3	0	0.01	-9999	-10000	0	0
PKN1	0	0	-9999	-10000	0	0
G2/M transition checkpoint	0.017	0.086	-9999	-0.5	21	21
MAP2K6	0.01	0.087	-9999	-0.53	21	21
MAPT	-0.016	0.13	-9999	-0.41	84	84
MAPK13	0.021	0.012	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	-0.002	0.027	-9999	-0.46	3	3

×

Retinoic acid receptors-mediated 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	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-10000	0	-10000	0	0
HDAC3	0	0	-10000	0	-10000	0	0
VDR	0	0	-10000	0	-10000	0	0
Cbp/p300/PCAF	0	0	-10000	0	-10000	0	0
EP300	0	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.039	0.034	-10000	0	-0.33	2	2
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0	0	-10000	0	-10000	0	0
AKT1	0.021	0.043	0.24	3	-0.36	6	9
RAR alpha/9cRA/Cyclin H	-0.01	0.06	-10000	0	-0.39	21	21
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.035	0.046	-10000	0	-0.36	8	8
CDC2	0.001	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.007	0.039	-10000	0	-0.29	1	1
NCOR2	0	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0	0	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	0.007	0.12	-10000	0	-0.58	24	24
NCOA2	-0.007	0.076	-10000	0	-0.84	7	7
NCOA3	0	0.01	-10000	0	-0.28	1	1
NCOA1	-0.001	0.029	-10000	0	-0.84	1	1
VDR/VDR/DNA	0	0	-10000	0	-10000	0	0
RARG	0	0	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
MAPK1	0	0	-10000	0	-10000	0	0
MAPK8	0	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.042	0.11	-10000	0	-0.64	21	21
RARA	0.016	0.054	-10000	0	-0.31	21	21
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.033	0.047	-10000	0	-0.28	11	11
PRKCA	-0.008	0.13	-10000	0	-0.77	24	24
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.004	0.13	-10000	0	-0.6	25	25
RXRG	-0.1	0.22	-10000	0	-0.46	221	221
RXRA	0.024	0.06	-10000	0	-0.34	21	21
RXRB	0.01	0.076	-10000	0	-0.45	21	21
VDR/Vit D3/DNA	0	0	-10000	0	-10000	0	0
RBP1	-0.022	0.094	-10000	0	-0.84	6	6
CRBP1/9-cic-RA	-0.015	0.069	-10000	0	-0.65	6	6
RARB	0.004	0.083	-10000	0	-0.84	8	8
PRKCG	-0.002	0.056	-10000	0	-0.28	34	34
MNAT1	0	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.027	0.12	-10000	0	-0.64	22	22
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.014	0.1	-10000	0	-0.5	23	23
proteasomal ubiquitin-dependent protein catabolic process	0.038	0.048	-10000	0	-0.43	2	2
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.004	0.13	-10000	0	-0.6	25	25
positive regulation of DNA binding	-0.009	0.057	-10000	0	-0.36	21	21
NRIP1	-0.003	0.12	-10000	0	-0.6	22	22
RXRs/RARs	-0.011	0.13	-10000	0	-0.59	25	25
RXRs/RXRs/DNA/9cRA	-0.045	0.12	-10000	0	-0.65	22	22
PRKACA	0	0	-10000	0	-10000	0	0
CDK7	0	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.005	0.029	-10000	0	-10000	0	0
CCNH	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

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	-0.015	0.085	-9999	-0.55	18	18
MAP4K1	-0.01	0.062	-9999	-0.32	27	27
MAP3K8	-0.005	0.065	-9999	-0.74	6	6
PRKCB	-0.018	0.11	-9999	-0.57	27	27
DBNL	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
MAP3K1	-0.006	0.047	-9999	-0.58	2	2
JUN	0.02	0.1	-9999	-0.58	23	23
MAP3K7	-0.006	0.047	-9999	-0.58	2	2
GRAP2	-0.014	0.1	-9999	-0.73	16	16
CRK	0	0	-9999	-10000	0	0
MAP2K4	0.044	0.058	-9999	-0.52	4	4
LAT	-0.004	0.048	-9999	-0.84	2	2
LCP2	0	0.01	-9999	-0.28	1	1
MAPK8	0.018	0.094	-9999	-0.68	14	14
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.007	0.05	-9999	-0.38	13	13
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.014	0.08	-9999	-0.54	16	16

×

BARD1 signaling events

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
BARD1/CSTF1	0	0.009	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
UBE2D3	0	0	-9999	-10000	0	0
PRKDC	-0.001	0.019	-9999	-0.28	4	4
ATR	0	0	-9999	-10000	0	0
UBE2L3	0	0	-9999	-10000	0	0
FANCD2	-0.001	0.007	-9999	-10000	0	0
protein ubiquitination	-0.018	0.038	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
M/R/N Complex	0	0	-9999	-10000	0	0
MRE11A	0	0	-9999	-10000	0	0
DNA-PK	-0.001	0.009	-9999	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.002	0.01	-9999	-10000	0	0
FANCF	0	0.01	-9999	-0.28	1	1
BRCA1	-0.001	0.014	-9999	-0.28	2	2
CCNE1	-0.054	0.11	-9999	-0.28	163	163
CDK2/Cyclin E1	-0.034	0.069	-9999	-10000	0	0
FANCG	0	0	-9999	-10000	0	0
BRCA1/BACH1/BARD1	-0.001	0.01	-9999	-10000	0	0
FANCE	0	0	-9999	-10000	0	0
FANCC	0	0	-9999	-10000	0	0
NBN	0	0	-9999	-10000	0	0
FANCA	-0.052	0.11	-9999	-10000	0	0
DNA repair	0.013	0.074	-9999	-10000	0	0
BRCA1/BARD1/ubiquitin	-0.001	0.01	-9999	-10000	0	0
BARD1/DNA-PK	-0.001	0.008	-9999	-10000	0	0
FANCL	0	0	-9999	-10000	0	0
mRNA polyadenylation	0	0.009	-9999	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0	0.001	-9999	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	0	0.008	-9999	-10000	0	0
BRCA1/BARD1/P53	0	0.007	-9999	-10000	0	0
BARD1/CSTF1/BRCA1	-0.001	0.009	-9999	-10000	0	0
BRCA1/BACH1	-0.001	0.014	-9999	-0.28	2	2
BARD1	0	0.01	-9999	-0.28	1	1
PCNA	-0.001	0.017	-9999	-10000	0	0
BRCA1/BARD1/UbcH5C	0	0.008	-9999	-10000	0	0
BRCA1/BARD1/UbcH7	0	0.008	-9999	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	-0.046	0.056	-9999	-10000	0	0
BARD1/DNA-PK/P53	-0.001	0.007	-9999	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.001	0.01	-9999	-10000	0	0
BRCA1/BARD1/CTIP	-0.001	0.008	-9999	-10000	0	0
FA complex	-0.004	0.009	-9999	-10000	0	0
BARD1/EWS	0	0.006	-9999	-10000	0	0
RBBP8	0.022	0.007	-9999	-10000	0	0
TP53	0	0	-9999	-10000	0	0
TOPBP1	0	0	-9999	-10000	0	0
G1/S transition of mitotic cell cycle	0	0.007	-9999	-10000	0	0
BRCA1/BARD1	-0.019	0.038	-9999	-10000	0	0
CSTF1	0	0.01	-9999	-10000	0	0
BARD1/EWS-Fli1	0	0.006	-9999	-10000	0	0
CDK2	0	0	-9999	-10000	0	0
UniProt:Q9BZD1	0	0	-9999	-10000	0	0
RAD51	-0.11	0.14	-9999	-0.28	341	341
RAD50	0	0	-9999	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.001	0.01	-9999	-10000	0	0
EWSR1	0	0	-9999	-10000	0	0

×

Aurora A 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	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.027	0.029	-9999	-10000	0	0
BIRC5	-0.2	0.12	-9999	-10000	0	0
NFKBIA	-0.025	0.031	-9999	-10000	0	0
CPEB1	-0.16	0.33	-9999	-0.84	163	163
AKT1	-0.025	0.031	-9999	-10000	0	0
NDEL1	0	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.024	0.026	-9999	-10000	0	0
NDEL1/TACC3	-0.038	0.056	-9999	-10000	0	0
GADD45A	0	0	-9999	-10000	0	0
GSK3B	0.001	0.003	-9999	-10000	0	0
PAK1/Aurora A	-0.03	0.037	-9999	-10000	0	0
MDM2	-0.001	0.019	-9999	-0.28	4	4
JUB	-0.004	0.058	-9999	-0.84	4	4
TPX2	-0.11	0.093	-9999	-10000	0	0
TP53	-0.011	0.015	-9999	-10000	0	0
DLG7	-0.033	0.033	-9999	-10000	0	0
AURKAIP1	0	0.01	-9999	-0.28	1	1
ARHGEF7	0	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.041	0.06	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.024	0.026	-9999	-10000	0	0
AURKA	-0.039	0.042	-9999	-10000	0	0
AURKB	-0.003	0.008	-9999	-10000	0	0
CDC25B	-0.018	0.024	-9999	-10000	0	0
G2/M transition checkpoint	-0.026	0.043	-9999	-0.53	4	4
mRNA polyadenylation	-0.13	0.21	-9999	-0.56	163	163
Aurora A/CPEB	-0.13	0.22	-9999	-0.56	163	163
Aurora A/TACC1/TRAP/chTOG	-0.026	0.077	-9999	-0.51	20	20
BRCA1	-0.001	0.014	-9999	-0.28	2	2
centrosome duplication	-0.03	0.037	-9999	-10000	0	0
regulation of centrosome cycle	-0.038	0.056	-9999	-10000	0	0
spindle assembly	-0.025	0.076	-9999	-0.5	20	20
TDRD7	0	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.1	0.065	-9999	-10000	0	0
CENPA	0.002	0.011	-9999	-10000	0	0
Aurora A/PP2A	-0.027	0.029	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.005	0.027	-9999	-10000	0	0
negative regulation of DNA binding	-0.011	0.015	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	-0.001	0.012	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.026	0.043	-9999	-0.53	4	4
mitotic prometaphase	-0.014	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.039	0.042	-9999	-10000	0	0
TACC1	-0.02	0.13	-9999	-0.84	20	20
TACC3	-0.041	0.099	-9999	-10000	0	0
Aurora A/Antizyme1	-0.02	0.02	-9999	-10000	0	0
Aurora A/RasGAP	-0.027	0.029	-9999	-10000	0	0
OAZ1	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.001	0.003	-9999	-10000	0	0
GIT1	-0.001	0.019	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	-0.003	0.021	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.11	0.093	-9999	-10000	0	0
PPP2R5D	0	0	-9999	-10000	0	0
Aurora A/TPX2	-0.11	0.081	-9999	-10000	0	0
PAK1	-0.006	0.04	-9999	-0.28	18	18
CKAP5	0	0	-9999	-10000	0	0

×

S1P5 pathway

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	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	0.024	0.079	0.51	5	-10000	0	5
GNAI2	0	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.004	0.038	-10000	0	-0.57	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.033	0.14	-10000	0	-0.84	21	21
RhoA/GTP	-0.024	0.081	-10000	0	-0.53	5	5
negative regulation of cAMP metabolic process	-0.027	0.09	-10000	0	-0.37	30	30
GNAZ	-0.006	0.07	-10000	0	-0.84	6	6
GNAI3	0	0	-10000	0	-10000	0	0
GNA12	0	0	-10000	0	-10000	0	0
S1PR5	-0.008	0.061	-10000	0	-0.38	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.028	0.091	-10000	0	-0.38	30	30
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
GNAI1	-0.043	0.18	-10000	0	-0.84	43	43

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.018	0.099	-9999	-0.6	24	24
KLHL20	-0.008	0.033	-9999	-0.25	2	2
CYFIP2	-0.009	0.06	-9999	-0.32	24	24
Rac1/GDP	0.048	0.07	-9999	-10000	0	0
ENAH	-0.017	0.098	-9999	-0.59	24	24
AP1M1	0	0	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.009	0.049	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.006	0.023	-9999	-0.17	2	2
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.089	-9999	-0.51	26	26
RAPGEF1	0.038	0.091	-9999	-0.49	24	24
CTNND1	0	0.01	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.018	0.1	-9999	-0.61	24	24
CRK	0.029	0.099	-9999	-0.55	24	24
E-cadherin/gamma catenin/alpha catenin	-0.017	0.095	-9999	-0.56	25	25
alphaE/beta7 Integrin	-0.005	0.039	-9999	-0.64	2	2
IQGAP1	0	0	-9999	-10000	0	0
NCKAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.002	0.031	-9999	-0.52	3	3
DLG1	-0.017	0.098	-9999	-0.59	24	24
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.006	0.035	-9999	-10000	0	0
MLLT4	-0.003	0.05	-9999	-0.84	3	3
ARF6/GTP/NME1/Tiam1	-0.006	0.027	-9999	-10000	0	0
PI3K	-0.008	0.046	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.02	0.11	-9999	-0.64	25	25
TIAM1	-0.001	0.019	-9999	-0.28	4	4
E-cadherin(dimer)/Ca2+	-0.014	0.081	-9999	-0.48	24	24
AKT1	-0.005	0.026	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
CDH1	-0.024	0.14	-9999	-0.84	24	24
RhoA/GDP	0.048	0.07	-9999	-10000	0	0
actin cytoskeleton organization	-0.006	0.024	-9999	-0.18	2	2
CDC42/GDP	0.048	0.07	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.011	0.06	-9999	-0.35	25	25
ITGB7	-0.007	0.055	-9999	-0.34	17	17
RAC1	0	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.015	0.085	-9999	-0.51	24	24
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.014	0.082	-9999	-0.49	24	24
mol:GDP	0.046	0.081	-9999	-0.42	24	24
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	-0.002	0.032	-9999	-0.46	3	3
p120 catenin/RhoA/GDP	-0.011	0.06	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.007	0.029	-9999	-0.21	6	6
NME1	-0.014	0.06	-9999	-0.28	41	41
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.018	0.099	-9999	-0.58	25	25
regulation of cell-cell adhesion	-0.008	0.043	-9999	-10000	0	0
WASF2	-0.003	0.012	-9999	-10000	0	0
Rap1/GTP	-0.01	0.057	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.017	0.085	-9999	-0.48	27	27
CCND1	-0.009	0.035	-9999	-0.26	6	6
VAV2	0.034	0.096	-9999	-0.52	24	24
RAP1/GDP	-0.01	0.057	-9999	-10000	0	0
adherens junction assembly	-0.017	0.096	-9999	-0.56	25	25
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0	0	-9999	-10000	0	0
PIP5K1C	0	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.016	0.08	-9999	-0.45	27	27
E-cadherin/beta catenin	-0.015	0.085	-9999	-0.51	24	24
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.017	0.098	-9999	-0.59	24	24
PIK3CA	0	0.01	-9999	-10000	0	0
Rac1/GTP	-0.011	0.054	-9999	-0.37	4	4
E-cadherin/beta catenin/alpha catenin	-0.016	0.093	-9999	-0.56	24	24
ITGAE	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.018	0.1	-9999	-0.63	24	24

×

IL2 signaling events mediated by PI3K

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.049	0.051	-10000	0	-10000	0	0
UGCG	0	0.027	-10000	0	-0.64	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	0.058	0.082	-10000	0	-0.38	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.024	0.03	-10000	0	-0.63	1	1
mol:DAG	0	0.002	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.022	0.08	-10000	0	-0.36	26	26
FRAP1	0.058	0.12	-10000	0	-0.38	47	47
FOXO3	0.065	0.099	-10000	0	-0.55	5	5
AKT1	0.06	0.1	-10000	0	-0.41	24	24
GAB2	-0.003	0.027	-10000	0	-0.28	8	8
SMPD1	-0.001	0.013	-10000	0	-10000	0	0
SGMS1	-0.001	0.013	-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	0.022	0.008	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
cell proliferation	0.039	0.056	-10000	0	-0.25	21	21
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	0	0.006	-10000	0	-10000	0	0
RPS6KB1	0.022	0.03	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.002	-10000	0	-10000	0	0
natural killer cell activation	0	0.002	-10000	0	-0.012	20	20
JAK3	0.008	0.034	-10000	0	-10000	0	0
PIK3R1	0.013	0.004	-10000	0	-10000	0	0
JAK1	0.013	0.004	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
MYC	0.048	0.18	-10000	0	-1	22	22
MYB	0.014	0.18	-10000	0	-1.3	14	14
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.057	0.08	-10000	0	-0.6	4	4
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.003	0.02	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.057	0.079	-10000	0	-0.58	4	4
Rac1/GDP	0	0.004	-10000	0	-10000	0	0
T cell proliferation	0.062	0.076	-10000	0	-0.5	5	5
SHC1	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.009	-10000	0	-0.067	14	14
PRKCZ	0.062	0.078	-10000	0	-0.52	5	5
NF kappa B1 p50/RelA	-0.021	0.078	-10000	0	-0.44	7	7
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.007	0.043	-10000	0	-0.54	2	2
HSP90AA1	0	0.01	-10000	0	-0.28	1	1
RELA	0	0	-10000	0	-10000	0	0
IL2RA	-0.028	0.11	-10000	0	-0.36	66	66
IL2RB	0.001	0.057	-10000	0	-10000	0	0
TERT	-0.034	0.091	-10000	0	-0.28	103	103
E2F1	0.025	0.061	-10000	0	-0.43	14	14
SOS1	0	0	-10000	0	-10000	0	0
RPS6	0	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.004	0.03	14	-10000	0	14
PTPN11	0	0	-10000	0	-10000	0	0
IL2RG	-0.003	0.085	-10000	0	-0.84	5	5
actin cytoskeleton organization	0.062	0.076	-10000	0	-0.5	5	5
GRB2	0	0.01	-10000	0	-10000	0	0
IL2	0.005	0.03	-10000	0	-10000	0	0
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
Rac1/GTP	0.03	0.009	-10000	0	-10000	0	0
LCK	-0.006	0.11	-10000	0	-0.46	34	34
BCL2	0.046	0.18	-10000	0	-0.9	26	26

×

S1P3 pathway

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	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.002	0.041	-9999	-0.84	2	2
mol:S1P	0.001	0.003	-9999	-10000	0	0
S1P1/S1P/Gi	-0.029	0.096	-9999	-0.37	50	50
GNAO1	-0.033	0.14	-9999	-0.84	21	21
S1P/S1P3/G12/G13	-0.001	0.013	-9999	-10000	0	0
AKT1	-0.01	0.046	-9999	-0.68	2	2
AKT3	0.018	0.17	-9999	-1.4	11	11
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.002	0.041	-9999	-0.84	2	2
GNAI2	0.001	0.003	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GNAI1	-0.043	0.18	-9999	-0.84	43	43
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.002	0.029	-9999	-0.28	9	9
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.01	0.1	-9999	-0.39	31	31
MAPK3	0.018	0.1	-9999	-0.53	9	9
MAPK1	0.018	0.1	-9999	-0.53	9	9
JAK2	0.02	0.1	-9999	-0.48	12	12
CXCR4	0.014	0.1	-9999	-0.48	14	14
FLT1	0.012	0.03	-9999	-0.85	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.018	0.1	-9999	-0.53	9	9
S1P/S1P3/Gi	0.01	0.11	-9999	-0.4	30	30
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.024	0.084	-9999	-0.51	9	9
VEGFA	0.01	0.03	-9999	-0.28	9	9
S1P/S1P2/Gi	-0.027	0.089	-9999	-0.38	30	30
VEGFR1 homodimer/VEGFA homodimer	0.02	0.031	-9999	-0.67	1	1
RHOA	0	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.005	0.037	-9999	-0.35	9	9
GNAQ	-0.002	0.041	-9999	-0.84	2	2
GNAZ	-0.006	0.071	-9999	-0.84	6	6
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.013	0.082	-9999	-0.4	27	27
GNA15	-0.002	0.035	-9999	-0.39	5	5
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	0	0	-9999	-10000	0	0
Rac1/GTP	-0.024	0.084	-9999	-0.51	9	9

×

IL1-mediated 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0.009	-10000	0	-10000	0	0
PRKCZ	-0.001	0.029	-10000	0	-0.84	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.005	0.034	-10000	0	-0.28	9	9
IRAK/TOLLIP	-0.001	0.008	-10000	0	-10000	0	0
IKBKB	-0.001	0.014	-10000	0	-0.28	2	2
IKBKG	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.033	0.13	-10000	0	-0.62	36	36
IL1A	-0.006	0.039	-10000	0	-0.28	17	17
IL1B	0.013	0.081	-10000	0	-0.7	10	10
IRAK/TRAF6/p62/Atypical PKCs	-0.001	0.016	-10000	0	-0.43	1	1
IL1R2	-0.039	0.17	-10000	0	-0.84	33	33
IL1R1	-0.01	0.091	-10000	0	-0.84	10	10
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.001	0.057	0.24	23	-0.33	9	32
TOLLIP	0	0.01	-10000	0	-0.28	1	1
TICAM2	0	0	-10000	0	-10000	0	0
MAP3K3	0	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0	0.005	-10000	0	-10000	0	0
IKK complex/ELKS	0	0.005	-10000	0	-10000	0	0
JUN	0.032	0.081	-10000	0	-0.41	26	26
MAP3K7	0	0.01	-10000	0	-0.28	1	1
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.012	0.08	-10000	0	-0.5	19	19
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.008	0.057	-10000	0	-0.51	10	10
PIK3R1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.008	0.053	-10000	0	-0.48	10	10
IL1 beta fragment/IL1R1/IL1RAP	-0.013	0.089	-10000	0	-0.56	19	19
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	0.03	0.067	-10000	0	-0.42	18	18
IRAK1	0.021	0.012	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.015	0.082	-10000	0	-0.64	12	12
IRAK4	0	0	-10000	0	-10000	0	0
PRKCI	0	0.01	-10000	0	-0.28	1	1
TRAF6	0	0	-10000	0	-10000	0	0
PI3K	0	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.007	0.05	-10000	0	-0.37	10	10
CHUK	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.013	0.089	-10000	0	-0.56	19	19
IL1 beta/IL1R2	-0.033	0.13	-10000	0	-0.58	42	42
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.007	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.01	0.07	-10000	0	-1.1	1	1
IRAK3	-0.025	0.14	-10000	0	-0.82	26	26
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.012	0.079	-10000	0	-0.5	19	19
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.005	0.037	-10000	0	-0.34	10	10
IL1 alpha/IL1R1/IL1RAP	-0.009	0.063	-10000	0	-0.56	10	10
RELA	0	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	-0.001	0.014	-10000	0	-10000	0	0
MYD88	0	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0	0.006	-10000	0	-10000	0	0
IL1RAP	0	0	-10000	0	-10000	0	0
UBE2N	0	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.009	0.063	-10000	0	-0.98	1	1
CASP1	-0.002	0.041	-10000	0	-0.84	2	2
IL1RN/IL1R2	-0.037	0.13	-10000	0	-0.63	37	37
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.012	0.084	-10000	0	-0.52	19	19
TMEM189-UBE2V1	-0.001	0.014	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.004	0.042	-10000	0	-0.38	10	10
PIK3CA	0	0.01	-10000	0	-10000	0	0
IL1RN	-0.012	0.065	-10000	0	-0.84	2	2
TRAF6/TAK1/TAB1/TAB2	0	0.006	-10000	0	-10000	0	0
MAP2K6	-0.01	0.065	-10000	0	-0.45	18	18

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0	0	-10000	0	-10000	0	0
NFATC1	0.048	0.025	-10000	0	-0.36	1	1
NFATC2	0.023	0.052	-10000	0	-0.26	4	4
NFATC3	-0.001	0.018	-10000	0	-0.53	1	1
YWHAE	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.012	0.096	-10000	0	-0.4	27	27
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	0	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.017	0.075	-10000	0	-0.53	10	10
BCL2/BAX	-0.018	0.11	-10000	0	-0.64	24	24
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.003	-10000	0	-10000	0	0
CaM/Ca2+	-0.001	0.003	-10000	0	-10000	0	0
BAX	0	0	-10000	0	-10000	0	0
MAPK14	0	0	-10000	0	-10000	0	0
BAD	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.019	0.082	-10000	0	-0.56	11	11
Calcineurin A alpha-beta B1/BCL2	-0.024	0.14	-10000	0	-0.84	24	24
FKBP8	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.019	0.081	0.55	11	-10000	0	11
KPNB1	0	0	-10000	0	-10000	0	0
KPNA2	-0.034	0.091	-10000	0	-0.28	102	102
XPO1	0	0	-10000	0	-10000	0	0
SFN	-0.016	0.11	-10000	0	-0.62	21	21
MAP3K8	-0.005	0.065	-10000	0	-0.74	6	6
NFAT4/CK1 alpha	0	0.012	-10000	0	-0.35	1	1
MEF2D/NFAT1/Cbp/p300	-0.036	0.097	-10000	0	-0.48	3	3
CABIN1	0.012	0.097	-10000	0	-0.4	27	27
CALM1	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
MAP3K1	0	0	-10000	0	-10000	0	0
CAMK4	-0.011	0.053	-10000	0	-0.28	32	32
mol:Ca2+	-0.001	0.006	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.01	0.041	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
MAPK8	0	0	-10000	0	-10000	0	0
MAPK9	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0	0.01	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.002	0.018	-10000	0	-0.42	1	1
PRKCH	-0.001	0.029	-10000	0	-0.84	1	1
CABIN1/Cbp/p300	-0.001	0.003	-10000	0	-10000	0	0
CASP3	0	0	-10000	0	-10000	0	0
PIM1	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.005	-10000	0	-10000	0	0
apoptosis	-0.006	0.033	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.003	0.027	-10000	0	-10000	0	0
PRKCB	-0.018	0.11	-10000	0	-0.57	27	27
PRKCE	-0.001	0.029	-10000	0	-0.84	1	1
JNK2/NFAT4	-0.001	0.017	-10000	0	-0.48	1	1
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0	0.01	-10000	0	-10000	0	0
NUP214	0	0	-10000	0	-10000	0	0
PRKCZ	-0.001	0.029	-10000	0	-0.84	1	1
PRKCA	-0.022	0.13	-10000	0	-0.77	24	24
PRKCG	-0.011	0.055	-10000	0	-0.28	34	34
PRKCQ	-0.036	0.16	-10000	0	-0.68	45	45
FKBP38/BCL2	-0.018	0.11	-10000	0	-0.64	24	24
EP300	0	0.001	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
NFATc/JNK1	0.047	0.031	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0.006	-10000	0	-10000	0	0
CSNK1A1	0.018	0.006	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.005	0.027	-10000	0	-10000	0	0
NFATc/ERK1	-0.001	0.016	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.017	0.074	-10000	0	-0.53	10	10
NR4A1	-0.074	0.22	-10000	0	-0.74	79	79
GSK3B	0	0	-10000	0	-10000	0	0
positive T cell selection	-0.001	0.018	-10000	0	-0.53	1	1
NFAT1/CK1 alpha	-0.011	0.031	-10000	0	-0.3	1	1
RCH1/ KPNB1	-0.021	0.057	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
AKAP5	-0.016	0.065	-10000	0	-10000	0	0
MEF2D	0	0.001	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	-0.001	0.017	-10000	0	-0.28	3	3
NFATc/p38 alpha	0.047	0.03	-10000	0	-10000	0	0
CREBBP	0	0.001	-10000	0	-10000	0	0
BCL2	-0.024	0.14	-10000	0	-0.84	24	24

×

S1P4 pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.033	0.14	-9999	-0.84	21	21
CDC42/GTP	-0.025	0.08	-9999	-0.57	2	2
PLCG1	-0.026	0.082	-9999	-0.58	2	2
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.025	0.078	-9999	-0.55	2	2
S1PR5	-0.008	0.061	-9999	-0.38	17	17
S1PR4	-0.011	0.08	-9999	-0.84	6	6
MAPK3	-0.026	0.082	-9999	-0.58	2	2
MAPK1	-0.026	0.082	-9999	-0.5	3	3
S1P/S1P5/Gi	-0.028	0.091	-9999	-0.38	30	30
GNAI1	-0.043	0.18	-9999	-0.84	43	43
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.004	0.038	-9999	-0.57	3	3
RHOA	-0.005	0.043	-9999	-0.48	6	6
S1P/S1P4/Gi	-0.029	0.089	-9999	-0.36	32	32
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.006	0.07	-9999	-0.84	6	6
S1P/S1P4/G12/G13	-0.006	0.046	-9999	-0.52	6	6
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.004	0.043	-10000	0	-0.51	6	6
HDAC3	0	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.015	-10000	0	-0.43	1	1
GATA1/HDAC4	-0.003	0.029	-10000	0	-0.64	1	1
GATA1/HDAC5	-0.002	0.019	-10000	0	-10000	0	0
GATA2/HDAC5	-0.017	0.098	-10000	0	-0.64	19	19
HDAC5/BCL6/BCoR	-0.002	0.033	-10000	0	-0.56	3	3
HDAC9	-0.01	0.078	-10000	0	-0.84	6	6
Glucocorticoid receptor/Hsp90/HDAC6	-0.005	0.051	-10000	0	-0.56	7	7
HDAC4/ANKRA2	-0.001	0.022	-10000	0	-0.64	1	1
HDAC5/YWHAB	0	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0	-10000	0	-10000	0	0
GATA2	-0.023	0.13	-10000	0	-0.84	19	19
HDAC4/RFXANK	-0.001	0.023	-10000	0	-0.64	1	1
BCOR	-0.001	0.029	-10000	0	-0.84	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0	0	-10000	0	-10000	0	0
HDAC5	0	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.005	0.054	-10000	0	-0.64	6	6
Histones	-0.002	0.024	-10000	0	-10000	0	0
ADRBK1	0	0.01	-10000	0	-0.28	1	1
HDAC4	-0.001	0.029	-10000	0	-0.84	1	1
XPO1	0	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0	0	-10000	0	-10000	0	0
HDAC4/Ubc9	-0.001	0.022	-10000	0	-0.64	1	1
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0	0	-10000	0	-10000	0	0
TUBA1B	0	0	-10000	0	-10000	0	0
HDAC6	0	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0	0.006	-10000	0	-10000	0	0
CAMK4	-0.011	0.053	-10000	0	-0.28	32	32
Tubulin/HDAC6	0	0.007	-10000	0	-10000	0	0
SUMO1	0	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
GATA1	-0.003	0.03	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
NR3C1	-0.007	0.076	-10000	0	-0.84	7	7
SUMO1/HDAC4	-0.001	0.016	-10000	0	-0.47	1	1
SRF	0	0	-10000	0	-10000	0	0
HDAC4/YWHAB	-0.001	0.022	-10000	0	-0.64	1	1
Tubulin	0	0.009	-10000	0	-10000	0	0
HDAC4/14-3-3 E	-0.001	0.022	-10000	0	-0.64	1	1
GNB1	0	0	-10000	0	-10000	0	0
RANGAP1	0	0	-10000	0	-10000	0	0
BCL6/BCoR	-0.002	0.038	-10000	0	-0.64	3	3
HDAC4/HDAC3/SMRT (N-CoR2)	-0.001	0.019	-10000	0	-0.56	1	1
HDAC4/SRF	-0.006	0.032	-10000	0	-0.56	1	1
HDAC4/ER alpha	-0.11	0.22	-10000	0	-0.64	118	118
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.002	0.024	-10000	0	-10000	0	0
cell motility	0	0.006	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0	0	-10000	0	-10000	0	0
BCL6	-0.002	0.041	-10000	0	-0.84	2	2
HDAC4/CaMK II delta B	-0.001	0.029	-10000	0	-0.84	1	1
Hsp90/HDAC6	0	0.006	-10000	0	-10000	0	0
ESR1	-0.15	0.29	-10000	0	-0.56	228	228
HDAC6/HDAC11	0	0.009	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
MEF2C	-0.001	0.029	-10000	0	-0.84	1	1
RAN	0	0	-10000	0	-10000	0	0
HDAC4/MEF2C	-0.001	0.023	-10000	0	-0.48	2	2
GNG2	-0.006	0.07	-10000	0	-0.84	6	6
NCOR2	0	0	-10000	0	-10000	0	0
TUBB2A	-0.001	0.014	-10000	0	-0.28	2	2
HDAC11	-0.001	0.014	-10000	0	-10000	0	0
HSP90AA1	0	0.01	-10000	0	-0.28	1	1
RANBP2	0	0	-10000	0	-10000	0	0
ANKRA2	0	0	-10000	0	-10000	0	0
RFXANK	0	0.01	-10000	0	-0.28	1	1
nuclear import	0.001	0.016	0.45	1	-10000	0	1

×

Sphingosine 1-phosphate (S1P) 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
SPHK2	0	0	-9999	-10000	0	0
SPHK1	-0.004	0.048	-9999	-0.84	2	2
GNAI2	0	0	-9999	-10000	0	0
mol:S1P	-0.001	0.018	-9999	-0.37	2	2
GNAO1	-0.033	0.14	-9999	-0.84	21	21
mol:Sphinganine-1-P	0.019	0.037	-9999	-0.64	2	2
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.001	0.013	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	-0.003	0.029	-9999	-0.28	9	9
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.001	0.016	-9999	-0.32	2	2
S1PR5	-0.008	0.061	-9999	-0.38	17	17
S1PR4	-0.011	0.08	-9999	-0.84	6	6
GNAI1	-0.043	0.18	-9999	-0.84	43	43
S1P/S1P5/G12	-0.004	0.036	-9999	-0.41	5	5
S1P/S1P3/Gq	-0.003	0.032	-9999	-0.29	9	9
S1P/S1P4/Gi	-0.027	0.086	-9999	-0.35	28	28
GNAQ	-0.002	0.041	-9999	-0.84	2	2
GNAZ	-0.006	0.07	-9999	-0.84	6	6
GNA14	-0.013	0.082	-9999	-0.4	27	27
GNA15	-0.002	0.035	-9999	-0.39	5	5
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	0	0	-9999	-10000	0	0
ABCC1	0	0	-9999	-10000	0	0

×

p38 MAPK signaling 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
TRAF6/ASK1	-0.001	0.024	-10000	0	-0.5	2	2
TRAF2/ASK1	-0.001	0.028	-10000	0	-0.57	2	2
ATM	0	0	-10000	0	-10000	0	0
MAP2K3	0.029	0.036	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.032	0.053	-10000	0	-0.37	4	4
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.015	0.063	-10000	0	-0.28	45	45
TXN	0	0.003	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
GADD45A	0	0	-10000	0	-10000	0	0
GADD45B	0	0	-10000	0	-10000	0	0
MAP3K1	0	0	-10000	0	-10000	0	0
MAP3K6	-0.001	0.029	-10000	0	-0.84	1	1
MAP3K7	0	0.01	-10000	0	-0.28	1	1
MAP3K4	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.002	0.038	-10000	0	-0.64	3	3
TAK1/TAB family	0	0.011	0.22	2	-10000	0	2
RAC1/OSM/MEKK3	0	0	-10000	0	-10000	0	0
TRAF2	0	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.004	0.015	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.076	0.23	-10000	0	-0.84	65	65
CCM2	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.05	0.15	-10000	0	-0.57	65	65
MAPK11	-0.002	0.041	-10000	0	-0.84	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.046	0.14	-10000	0	-0.52	67	67
OSM/MEKK3	0	0	-10000	0	-10000	0	0
TAOK1	-0.003	0.038	-10000	0	-0.46	6	6
TAOK2	0	0	-10000	0	-10000	0	0
TAOK3	0	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	-0.002	0.041	-10000	0	-0.84	2	2
MAP3K10	0	0	-10000	0	-10000	0	0
MAP3K3	0	0	-10000	0	-10000	0	0
TRX/ASK1	-0.001	0.027	-10000	0	-0.56	2	2
GADD45/MTK1/MTK1	-0.005	0.023	-10000	0	-10000	0	0

×

mTOR signaling pathway

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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0	0	-10000	0	-10000	0	0
mol:PIP3	-0.012	0.067	0.34	1	-0.35	30	31
FRAP1	0.012	0.015	-10000	0	-10000	0	0
AKT1	-0.011	0.057	0.24	1	-0.52	1	2
INSR	0	0.01	-10000	0	-0.28	1	1
Insulin Receptor/Insulin	0	0.005	-10000	0	-10000	0	0
mol:GTP	-0.009	0.042	-10000	0	-0.41	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.002	0.012	-10000	0	-10000	0	0
TSC2	0	0	-10000	0	-10000	0	0
RHEB/GDP	-0.007	0.036	-10000	0	-0.36	1	1
TSC1	0	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.016	0.081	-10000	0	-0.43	31	31
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.003	0.015	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.021	0.034	-10000	0	-0.28	1	1
MAP3K5	0.009	0.023	-10000	0	-0.45	2	2
PIK3R1	0	0	-10000	0	-10000	0	0
apoptosis	0.009	0.023	-10000	0	-0.45	2	2
mol:LY294002	0	0	-10000	0	-0.002	31	31
EIF4B	0.028	0.031	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.004	0.022	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0.003	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.014	0.072	-10000	0	-0.38	31	31
mTOR/RHEB/GTP/Raptor/GBL	0.028	0.023	0.18	1	-10000	0	1
FKBP1A	0	0.01	-10000	0	-10000	0	0
RHEB/GTP	-0.007	0.035	-10000	0	-0.35	1	1
mol:Amino Acids	0	0	-10000	0	-0.002	31	31
FKBP12/Rapamycin	0	0.006	-10000	0	-10000	0	0
PDPK1	-0.011	0.06	0.26	1	-0.32	30	31
EIF4E	0	0	-10000	0	-10000	0	0
ASK1/PP5C	-0.002	0.031	-10000	0	-0.63	2	2
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.016	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.009	0.045	-10000	0	-0.44	1	1
tumor necrosis factor receptor activity	0	0	0.002	31	-10000	0	31
RPS6	0	0	-10000	0	-10000	0	0
PPP5C	0	0	-10000	0	-10000	0	0
EIF4G1	0	0	-10000	0	-10000	0	0
IRS1	-0.009	0.088	-10000	0	-0.46	31	31
INS	0	0	-10000	0	-10000	0	0
PTEN	-0.002	0.041	-10000	0	-0.84	2	2
PDK2	-0.013	0.069	0.26	1	-0.34	33	34
EIF4EBP1	0.013	0.014	-10000	0	-10000	0	0
PIK3CA	0	0.01	-10000	0	-10000	0	0
PPP2R5D	0.019	0.014	-10000	0	-10000	0	0
peptide biosynthetic process	0	0.004	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
EIF4A1	0	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.003	2	-10000	0	2
EEF2	0	0.004	-10000	0	-10000	0	0
eIF4E/4E-BP1	0	0	-10000	0	-10000	0	0

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.013	0.033	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.006	0.024	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.001	0.003	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.008	0.031	-9999	-10000	0	0
CaM/Ca2+	0.012	0.029	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.011	0.031	-9999	-10000	0	0
AKT1	-0.006	0.014	-9999	-10000	0	0
MAP2K1	0.041	0.037	-9999	-10000	0	0
MAP3K11	-0.003	0.028	-9999	-10000	0	0
IFNGR1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.027	0.1	-9999	-0.42	20	20
Rap1/GTP	-0.003	0.008	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.013	0.032	-9999	-10000	0	0
CEBPB	0.075	0.033	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.011	0.058	-9999	-1.3	1	1
STAT1	-0.011	0.031	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.039	0.096	-9999	-0.27	124	124
PIK3CA	0	0.01	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	-0.008	0.028	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	0	0.006	-9999	-10000	0	0
mol:Ca2+	0.012	0.031	-9999	-10000	0	0
MAPK3	0.055	0.033	-9999	-10000	0	0
STAT1 (dimer)	-0.002	0.046	-9999	-10000	0	0
MAPK1	0.055	0.033	-9999	-10000	0	0
JAK2	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
JAK1	0	0	-9999	-10000	0	0
CAMK2D	-0.003	0.05	-9999	-0.84	3	3
DAPK1	0.069	0.031	-9999	-10000	0	0
SMAD7	0.051	0.035	-9999	-10000	0	0
CBL/CRKL/C3G	-0.006	0.014	-9999	-10000	0	0
PI3K	0.01	0.026	-9999	-10000	0	0
IFNG	-0.039	0.096	-9999	-0.27	124	124
apoptosis	0.054	0.025	-9999	-10000	0	0
CAMK2G	0	0	-9999	-10000	0	0
STAT3 (dimer)	0	0	-9999	-10000	0	0
CAMK2A	-0.008	0.046	-9999	-10000	0	0
CAMK2B	-0.076	0.23	-9999	-0.84	65	65
FRAP1	0.043	0.033	-9999	-10000	0	0
PRKCD	-0.006	0.014	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
negative regulation of cell growth	-0.008	0.031	-9999	-10000	0	0
PTPN2	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
IRF1	0.065	0.044	-9999	-10000	0	0
STAT1 (dimer)/PIASy	-0.008	0.029	-9999	-10000	0	0
SOCS1	0.001	0.055	-9999	-1.5	1	1
mol:GDP	-0.006	0.014	-9999	-10000	0	0
CASP1	0.05	0.039	-9999	-0.36	2	2
PTGES2	0	0	-9999	-10000	0	0
IRF9	0.057	0.018	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.007	0.02	-9999	-10000	0	0
RAP1/GDP	-0.003	0.008	-9999	-10000	0	0
CBL	-0.009	0.021	-9999	-10000	0	0
MAP3K1	0.031	0.038	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
PIAS4	0	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.008	0.031	-9999	-10000	0	0
PTPN11	-0.01	0.025	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0

×

VEGFR1 specific signals

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	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	-0.001	0.032	-9999	-0.94	1	1
VEGFR1 homodimer/NRP1	-0.001	0.033	-9999	-0.95	1	1
mol:DAG	0.038	0.036	-9999	-0.68	2	2
VEGFR1 homodimer/NRP1/VEGFR 121	-0.002	0.033	-9999	-0.88	1	1
CaM/Ca2+	-0.002	0.032	-9999	-0.64	2	2
HIF1A	0	0.013	-9999	-0.39	1	1
GAB1	0	0	-9999	-10000	0	0
AKT1	-0.001	0.03	-9999	-0.74	1	1
PLCG1	0.038	0.036	-9999	-0.68	2	2
NOS3	0.063	0.032	-9999	-0.58	2	2
CBL	0	0	-9999	-10000	0	0
mol:NO	0.062	0.031	-9999	-0.56	2	2
FLT1	0.028	0.037	-9999	-1	1	1
PGF	-0.001	0.029	-9999	-0.84	1	1
VEGFR1 homodimer/NRP2/VEGFR121	-0.003	0.047	-9999	-1.3	1	1
CALM1	0	0	-9999	-10000	0	0
PIK3CA	0	0.01	-9999	-10000	0	0
eNOS/Hsp90	-0.001	0.027	-9999	-0.67	1	1
endothelial cell proliferation	0.037	0.094	-9999	-0.89	3	3
mol:Ca2+	0.038	0.036	-9999	-0.67	2	2
MAPK3	0.039	0.088	-9999	-0.48	21	21
MAPK1	0.039	0.088	-9999	-0.48	21	21
PIK3R1	0	0	-9999	-10000	0	0
PLGF homodimer	-0.001	0.029	-9999	-0.84	1	1
PRKACA	0	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.17	0.34	-9999	-0.84	174	174
VEGFA homodimer	-0.003	0.029	-9999	-0.28	9	9
VEGFR1 homodimer/VEGFA homodimer	-0.002	0.035	-9999	-0.94	1	1
platelet activating factor biosynthetic process	0.046	0.085	-9999	-1.1	1	1
PI3K	-0.002	0.033	-9999	-0.65	2	2
PRKCA	0.032	0.093	-9999	-0.51	22	22
PRKCB	0.035	0.081	-9999	-0.52	15	15
VEGFR1 homodimer/PLGF homodimer	-0.002	0.038	-9999	-0.75	2	2
VEGFA	-0.003	0.029	-9999	-0.28	9	9
VEGFB	0	0	-9999	-10000	0	0
mol:IP3	0.038	0.036	-9999	-0.68	2	2
RASA1	0.039	0.031	-9999	-0.87	1	1
NRP2	-0.001	0.03	-9999	-0.56	2	2
VEGFR1 homodimer	0.028	0.037	-9999	-1	1	1
VEGFB homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.083	0.17	-9999	-0.93	2	2
PTPN11	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.002	0.032	-9999	-0.64	2	2
mol:L-citrulline	0.062	0.031	-9999	-0.56	2	2
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.002	0.031	-9999	-0.83	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.002	0.032	-9999	-0.88	1	1
CD2AP	0	0.01	-9999	-10000	0	0
PI3K/GAB1	-0.001	0.031	-9999	-0.78	1	1
PDPK1	-0.002	0.03	-9999	-0.76	1	1
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.002	0.032	-9999	-0.88	1	1
mol:NADP	0.062	0.031	-9999	-0.56	2	2
HSP90AA1	0	0.01	-9999	-0.28	1	1
ubiquitin-dependent protein catabolic process	-0.002	0.03	-9999	-0.82	1	1
VEGFR1 homodimer/NRP2	-0.002	0.049	-9999	-1.4	1	1

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0	0	-9999	-10000	0	0
SMAD2	0.014	0	-9999	-10000	0	0
SMAD3	0.041	0	-9999	-10000	0	0
SMAD3/SMAD4	0	0	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.01	0.027	-9999	-10000	0	0
PPM1A	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
SMAD2/SMAD4	0	0	-9999	-10000	0	0
MAP3K1	0	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.002	0.031	-9999	-0.64	2	2
MAPK3	0	0	-9999	-10000	0	0
MAPK1	0	0	-9999	-10000	0	0
NUP214	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
CTDSP2	0	0	-9999	-10000	0	0
CTDSPL	0	0	-9999	-10000	0	0
KPNB1	0	0	-9999	-10000	0	0
TGFBRAP1	-0.002	0.041	-9999	-0.84	2	2
UBE2I	0	0	-9999	-10000	0	0
NUP153	0	0.01	-9999	-10000	0	0
KPNA2	-0.034	0.091	-9999	-0.28	102	102
PIAS4	0	0	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.007	0.055	-9999	-0.34	17	17
ITGA4	-0.003	0.03	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.007	0.046	-9999	-0.45	6	6
alpha4/beta1 Integrin	-0.002	0.019	-9999	-10000	0	0

×

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

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
BAG4	-0.003	0.03	-9999	-0.28	10	10
Caspase 8 (4 units)	-0.007	0.045	-9999	-1	1	1
NEF	-0.004	0.022	-9999	-0.22	4	4
NFKBIA	-0.001	0.011	-9999	-10000	0	0
BIRC3	-0.01	0.08	-9999	-0.84	7	7
CYCS	0.042	0.055	-9999	-0.98	1	1
RIPK1	0	0	-9999	-10000	0	0
CD247	-0.026	0.13	-9999	-0.64	30	30
MAP2K7	0.043	0.046	-9999	-0.82	1	1
protein ubiquitination	0.066	0.033	-9999	-10000	0	0
CRADD	0	0	-9999	-10000	0	0
DAXX	0	0	-9999	-10000	0	0
FAS	-0.002	0.041	-9999	-0.84	2	2
BID	-0.008	0.05	-9999	-1.1	1	1
NF-kappa-B/RelA/I kappa B alpha	-0.004	0.034	-9999	-10000	0	0
TRADD	0	0	-9999	-10000	0	0
MAP3K5	-0.002	0.041	-9999	-0.84	2	2
CFLAR	0	0	-9999	-10000	0	0
FADD	-0.005	0.038	-9999	-0.28	16	16
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.004	0.034	-9999	-0.34	7	7
MAPK8	0.049	0.043	-9999	-0.75	1	1
APAF1	0	0	-9999	-10000	0	0
TRAF1	-0.001	0.017	-9999	-10000	0	0
TRAF2	0	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.009	0.054	-9999	-0.43	7	7
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.002	0.03	-9999	-0.39	1	1
CHUK	0.068	0.034	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.004	0.045	-9999	-0.67	3	3
TCRz/NEF	-0.024	0.11	-9999	-0.55	29	29
TNF	-0.016	0.098	-9999	-0.84	10	10
FASLG	-0.003	0.13	-9999	-0.61	29	29
NFKB1	-0.001	0.011	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.011	0.065	-9999	-0.56	10	10
CASP6	-0.003	0.03	-9999	-0.72	1	1
CASP7	0.074	0.075	-9999	-0.64	7	7
RELA	-0.001	0.011	-9999	-10000	0	0
CASP2	0	0	-9999	-10000	0	0
CASP3	0.074	0.075	-9999	-0.64	7	7
TNFRSF1A	0	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.002	0.019	-9999	-10000	0	0
CASP8	0	0	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
MAP3K14	0.063	0.037	-9999	-0.36	1	1
APAF-1/Caspase 9	-0.008	0.054	-9999	-0.54	7	7
BCL2	0.042	0.089	-9999	-0.43	25	25

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.012	0.083	-9999	-0.64	14	14
AKT1	0.085	0.044	-9999	-0.69	2	2
PTK2B	-0.01	0.072	-9999	-0.98	2	2
VEGFR2 homodimer/Frs2	-0.004	0.047	-9999	-0.93	2	2
CAV1	-0.17	0.34	-9999	-0.84	174	174
CALM1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.004	0.044	-9999	-0.87	2	2
endothelial cell proliferation	0.086	0.071	-9999	-0.65	3	3
mol:Ca2+	0.054	0.043	-9999	-0.78	2	2
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.001	0.041	-9999	-0.82	2	2
RP11-342D11.1	0.046	0.043	-9999	-0.78	2	2
CDH5	-0.004	0.058	-9999	-0.84	4	4
VEGFA homodimer	-0.001	0.011	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
SHC2	-0.024	0.14	-9999	-0.84	24	24
HRAS/GDP	-0.001	0.033	-9999	-0.66	2	2
SH2D2A	-0.029	0.088	-9999	-0.28	86	86
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0	0.034	-9999	-0.63	2	2
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.013	0.056	-9999	-0.78	3	3
VEGFR1 homodimer	-0.001	0.029	-9999	-0.84	1	1
SHC/GRB2/SOS1	-0.001	0.037	-9999	-0.75	2	2
GRB10	-0.003	0.039	-9999	-0.78	2	2
PTPN11	0	0	-9999	-10000	0	0
GRB2	0	0.01	-9999	-10000	0	0
PAK1	-0.006	0.04	-9999	-0.28	18	18
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.003	0.064	-9999	-1.2	2	2
HRAS	0	0.01	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.005	0.04	-9999	-0.52	2	2
HIF1A	0	0	-9999	-10000	0	0
FRS2	-0.003	0.03	-9999	-0.28	10	10
oxygen and reactive oxygen species metabolic process	-0.001	0.04	-9999	-0.81	2	2
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.002	0.041	-9999	-0.84	2	2
Nck/Pak	-0.004	0.025	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.004	0.055	-9999	-1.1	2	2
mol:GDP	-0.001	0.036	-9999	-0.72	2	2
mol:NADP	0.076	0.031	-9999	-0.52	2	2
eNOS/Hsp90	0.077	0.029	-9999	-0.49	2	2
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	-0.003	0.039	-9999	-0.79	2	2
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	-0.001	0.03	-9999	-0.84	1	1
VEGFA	-0.003	0.028	-9999	-10000	0	0
VEGFC	0	0	-9999	-10000	0	0
FAK1/Vinculin	-0.006	0.055	-9999	-0.9	2	2
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.008	0.078	-9999	-1	2	2
PTPN6	-0.001	0.014	-9999	-0.28	2	2
EPAS1	-0.001	0.019	-9999	-0.38	2	2
mol:L-citrulline	0.076	0.031	-9999	-0.52	2	2
ITGAV	0	0	-9999	-10000	0	0
PIK3CA	0	0.01	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0	0.042	-9999	-0.82	2	2
VEGFR2 homodimer/VEGFA homodimer	-0.001	0.043	-9999	-0.86	2	2
VEGFR2/3 heterodimer	-0.003	0.061	-9999	-0.96	3	3
VEGFB	0	0	-9999	-10000	0	0
MAPK11	0.059	0.044	-9999	-0.8	2	2
VEGFR2 homodimer	0.032	0.052	-9999	-1	2	2
FLT1	-0.001	0.029	-9999	-0.84	1	1
NEDD4	0	0	-9999	-10000	0	0
MAPK3	0.055	0.064	-9999	-0.8	3	3
MAPK1	0.055	0.064	-9999	-0.8	3	3
VEGFA145/NRP2	-0.003	0.029	-9999	-0.64	1	1
VEGFR1/2 heterodimer	-0.003	0.058	-9999	-1.2	2	2
KDR	0.032	0.052	-9999	-1	2	2
VEGFA165/NRP1/VEGFR2 homodimer	-0.001	0.051	-9999	-1	2	2
SRC	0	0.01	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.057	0.064	-9999	-1	2	2
PI3K	-0.003	0.049	-9999	-0.91	2	2
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.003	0.043	-9999	-0.87	2	2
FES	-0.004	0.048	-9999	-0.81	2	2
GAB1	-0.002	0.047	-9999	-0.95	2	2
VEGFR2 homodimer/VEGFA homodimer/Src	-0.003	0.043	-9999	-0.87	2	2
CTNNB1	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.009	0.17	-9999	-0.55	5	5
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.004	0.046	-9999	-0.74	3	3
PI3K/GAB1	-0.002	0.038	-9999	-0.71	2	2
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.002	0.043	-9999	-0.79	2	2
PRKACA	0	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.003	0.057	-9999	-0.9	3	3
HSP90AA1	0	0.01	-9999	-0.28	1	1
CDC42	-0.003	0.04	-9999	-0.81	2	2
actin cytoskeleton reorganization	-0.013	0.056	-9999	-0.77	3	3
PTK2	0.061	0.07	-9999	-1	2	2
EDG1	0.046	0.043	-9999	-0.78	2	2
mol:DAG	-0.003	0.039	-9999	-0.79	2	2
CaM/Ca2+	-0.002	0.036	-9999	-0.72	2	2
MAP2K3	0.062	0.042	-9999	-0.76	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.001	0.041	-9999	-0.82	2	2
PLCG1	-0.003	0.04	-9999	-0.81	2	2
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.001	0.044	-9999	-0.82	2	2
IQGAP1	0	0	-9999	-10000	0	0
YES1	-0.001	0.029	-9999	-0.84	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.003	0.043	-9999	-0.87	2	2
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.003	0.044	-9999	-0.87	2	2
cell migration	0.086	0.059	-9999	-0.79	2	2
mol:PI-3-4-5-P3	-0.002	0.043	-9999	-0.8	2	2
FYN	-0.001	0.029	-9999	-0.84	1	1
VEGFB/NRP1	-0.002	0.037	-9999	-0.74	2	2
mol:NO	0.076	0.031	-9999	-0.52	2	2
PXN	0	0	-9999	-10000	0	0
HRAS/GTP	-0.002	0.033	-9999	-0.66	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.001	0.041	-9999	-0.82	2	2
VHL	0	0	-9999	-10000	0	0
ITGB3	-0.015	0.11	-9999	-0.84	14	14
NOS3	0.078	0.035	-9999	-0.6	2	2
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.017	0.093	-9999	-0.52	26	26
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.049	0.092	-9999	-0.95	2	2
PRKCB	0.051	0.087	-9999	-1.2	2	2
VCL	0	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.001	0.04	-9999	-0.79	2	2
VEGFR1/2 heterodimer/VEGFA homodimer	-0.004	0.055	-9999	-1.1	2	2
VEGFA165/NRP2	-0.003	0.029	-9999	-0.64	1	1
MAPKKK cascade	0	0.034	-9999	-0.66	2	2
NRP2	-0.001	0.03	-9999	-0.56	2	2
VEGFC homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
ROCK1	0	0	-9999	-10000	0	0
FAK1/Paxillin	-0.006	0.055	-9999	-0.9	2	2
MAP3K13	-0.003	0.04	-9999	-0.81	2	2
PDPK1	0.078	0.043	-9999	-0.68	2	2

×

Class I PI3K signaling events

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
ARF5/GTP	0	0.021	0.3	2	-10000	0	2
DAPP1	0.036	0.051	-10000	0	-0.54	3	3
Src family/SYK family/BLNK-LAT/BTK-ITK	0.047	0.079	-10000	0	-0.54	8	8
mol:DAG	0.054	0.049	0.21	1	-0.27	5	6
HRAS	0	0.009	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
ARF5/GDP	-0.001	0.016	-10000	0	-10000	0	0
PLCG2	-0.001	0.03	-10000	0	-0.56	2	2
PLCG1	0	0	-10000	0	-10000	0	0
ARF5	0	0.01	-10000	0	-10000	0	0
mol:GTP	0	0.02	-10000	0	-0.42	1	1
ARF1/GTP	0	0.02	0.28	2	-10000	0	2
RHOA	0	0	-10000	0	-10000	0	0
YES1	-0.001	0.029	-10000	0	-0.84	1	1
RAP1A/GTP	0	0.02	-10000	0	-0.42	1	1
ADAP1	-0.002	0.033	-10000	0	-0.44	3	3
ARAP3	0	0.02	0.27	2	-0.42	1	3
INPPL1	0	0	-10000	0	-10000	0	0
PREX1	-0.01	0.052	-10000	0	-10000	0	0
ARHGEF6	-0.005	0.064	-10000	0	-0.84	5	5
ARHGEF7	0	0	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
NRAS	-0.001	0.013	-10000	0	-10000	0	0
FYN	-0.001	0.029	-10000	0	-0.84	1	1
ARF6	0	0	-10000	0	-10000	0	0
FGR	0	0.01	-10000	0	-0.28	1	1
mol:Ca2+	0.04	0.028	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.001	0.019	-10000	0	-0.28	4	4
ZAP70	-0.027	0.13	-10000	0	-0.51	44	44
mol:IP3	0.049	0.037	-10000	0	-10000	0	0
LYN	0	0	-10000	0	-10000	0	0
ARF1/GDP	-0.001	0.015	-10000	0	-10000	0	0
RhoA/GDP	0	0.019	0.28	2	-10000	0	2
PDK1/Src/Hsp90	0	0.007	-10000	0	-10000	0	0
BLNK	0	0	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.064	0.024	-10000	0	-10000	0	0
SRC	0	0.01	-10000	0	-10000	0	0
PLEKHA2	0.03	0.006	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PTEN	-0.002	0.04	-10000	0	-0.82	2	2
HSP90AA1	0	0.01	-10000	0	-0.28	1	1
ARF6/GTP	0	0.02	0.3	2	-10000	0	2
RhoA/GTP	0	0.019	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.01	0.057	-10000	0	-0.55	4	4
BLK	-0.036	0.1	-10000	0	-0.3	102	102
PDPK1	0	0	-10000	0	-10000	0	0
CYTH1	0	0.019	-10000	0	-10000	0	0
HCK	-0.004	0.033	-10000	0	-10000	0	0
CYTH3	0	0.019	-10000	0	-10000	0	0
CYTH2	0	0.019	-10000	0	-10000	0	0
KRAS	0	0.009	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.003	0.049	-10000	0	-0.56	6	6
SGK1	-0.003	0.05	0.24	2	-0.69	4	6
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.036	0.021	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
SYK	0	0.01	-10000	0	-10000	0	0
ARF6/GDP	0	0.02	0.29	2	-10000	0	2
mol:PI-3-4-5-P3	0	0.024	0.37	2	-0.42	1	3
ARAP3/RAP1A/GTP	0	0.02	-10000	0	-0.42	1	1
VAV1	-0.002	0.032	-10000	0	-0.46	3	3
mol:PI-3-4-P2	0.022	0	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0	0.016	-10000	0	-0.42	1	1
PLEKHA1	0.029	0.021	-10000	0	-0.56	1	1
Rac1/GDP	-0.001	0.015	-10000	0	-10000	0	0
LAT	-0.004	0.048	-10000	0	-0.84	2	2
Rac1/GTP	-0.002	0.028	-10000	0	-0.34	5	5
ITK	-0.017	0.08	-10000	0	-0.46	24	24
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.061	0.063	0.24	1	-0.38	5	6
LCK	-0.019	0.1	-10000	0	-0.46	34	34
BTK	0	0.02	-10000	0	-10000	0	0

×

Circadian rhythm pathway

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
chromatin modification	0.001	0.019	-9999	-10000	0	0
CLOCK	0	0.001	-9999	-10000	0	0
TIMELESS/CRY2	-0.001	0.008	-9999	-10000	0	0
DEC1/BMAL1	-0.001	0.01	-9999	-10000	0	0
ATR	0	0	-9999	-10000	0	0
NR1D1	0.042	0.011	-9999	-10000	0	0
ARNTL	0	0.001	-9999	-10000	0	0
TIMELESS	0.041	0.014	-9999	-10000	0	0
NPAS2	-0.005	0.06	-9999	-0.59	7	7
CRY2	0	0	-9999	-10000	0	0
mol:CO	-0.013	0.003	-9999	-10000	0	0
CHEK1	-0.008	0.046	-9999	-0.28	24	24
mol:HEME	0.013	0.003	-9999	-10000	0	0
PER1	-0.018	0.12	-9999	-0.84	18	18
BMAL/CLOCK/NPAS2	-0.003	0.038	-9999	-0.55	4	4
BMAL1/CLOCK	0.046	0.026	-9999	-10000	0	0
S phase of mitotic cell cycle	0.001	0.019	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.001	0.019	-9999	-10000	0	0
mol:NADPH	0.013	0.003	-9999	-10000	0	0
PER1/TIMELESS	-0.011	0.071	-9999	-0.49	18	18
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.001	0.017	-9999	-0.28	3	3

×

HIF-2-alpha transcription factor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0.001	0.014	-10000	0	-10000	0	0
oxygen homeostasis	0.013	0.012	-10000	0	-10000	0	0
TCEB2	-0.001	0.019	-10000	0	-0.28	4	4
TCEB1	-0.001	0.017	-10000	0	-0.28	3	3
VHL/Elongin B/Elongin C/HIF2A	-0.003	0.023	-10000	0	-10000	0	0
EPO	0.16	0.14	-10000	0	-10000	0	0
FIH (dimer)	0.023	0.011	-10000	0	-10000	0	0
APEX1	0.022	0.009	-10000	0	-10000	0	0
SERPINE1	0.17	0.14	-10000	0	-0.59	1	1
FLT1	-0.001	0.073	-10000	0	-1.4	2	2
ADORA2A	0.15	0.14	-10000	0	-0.55	2	2
germ cell development	0.17	0.13	-10000	0	-0.66	1	1
SLC11A2	0.17	0.13	-10000	0	-0.59	1	1
BHLHE40	0.17	0.14	-10000	0	-0.98	2	2
HIF1AN	0.023	0.011	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.02	0.064	-10000	0	-0.39	1	1
ETS1	0.024	0.044	-10000	0	-0.87	2	2
CITED2	0.001	0.009	-10000	0	-10000	0	0
KDR	-0.002	0.086	-10000	0	-1.7	2	2
PGK1	0.17	0.13	-10000	0	-0.59	1	1
SIRT1	0	0	-10000	0	-10000	0	0
response to hypoxia	-0.001	0.003	-10000	0	-10000	0	0
HIF2A/ARNT	0.17	0.15	-10000	0	-0.57	4	4
EPAS1	0.1	0.072	-10000	0	-0.41	1	1
SP1	0.018	0.002	-10000	0	-10000	0	0
ABCG2	0.14	0.23	-10000	0	-0.71	50	50
EFNA1	0.17	0.13	-10000	0	-0.59	1	1
FXN	0.16	0.13	-10000	0	-0.57	1	1
POU5F1	0.17	0.14	-10000	0	-0.69	1	1
neuron apoptosis	-0.056	0.13	0.56	4	-10000	0	4
EP300	0	0	-10000	0	-10000	0	0
EGLN3	0	0.08	-10000	0	-0.28	39	39
EGLN2	0.022	0.02	-10000	0	-0.26	3	3
EGLN1	0.022	0.032	-10000	0	-0.85	1	1
VHL/Elongin B/Elongin C	-0.001	0.012	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.023	0.009	-10000	0	-10000	0	0
SLC2A1	0.16	0.14	-10000	0	-0.55	2	2
TWIST1	0.15	0.19	-10000	0	-0.7	25	25
ELK1	0.018	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.012	0.056	-10000	0	-10000	0	0
VEGFA	0.17	0.14	-10000	0	-0.59	1	1
CREBBP	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.005	0.057	-9999	-0.52	10	10
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.005	0.046	-9999	-0.42	10	10
SUMO1	0	0	-9999	-10000	0	0
ZFPM1	-0.001	0.014	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
FKBP3	0	0	-9999	-10000	0	0
Histones	-0.003	0.023	-9999	-10000	0	0
YY1/LSF	0	0	-9999	-10000	0	0
SMG5	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.005	0.041	-9999	-0.38	10	10
I kappa B alpha/HDAC1	-0.004	0.028	-9999	-10000	0	0
SAP18	0	0	-9999	-10000	0	0
RELA	-0.004	0.035	-9999	-0.33	10	10
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
HDAC3/TR2	-0.004	0.028	-9999	-10000	0	0
NuRD/MBD3 Complex	0	0.001	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.004	0.032	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.023	0.13	-9999	-0.84	19	19
GATA1	-0.003	0.03	-9999	-10000	0	0
Mad/Max	0	0.006	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0	0.003	-9999	-10000	0	0
RBBP7	-0.003	0.027	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0	0	-9999	-10000	0	0
MAX	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NFKBIA	-0.004	0.032	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0	0.001	-9999	-10000	0	0
SIN3 complex	0	0.007	-9999	-10000	0	0
SMURF1	0	0	-9999	-10000	0	0
CHD3	0	0	-9999	-10000	0	0
SAP30	-0.001	0.017	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	-0.001	0.029	-9999	-0.84	1	1
YY1/HDAC3	-0.003	0.024	-9999	-10000	0	0
YY1/HDAC2	0	0	-9999	-10000	0	0
YY1/HDAC1	0	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0	0.001	-9999	-10000	0	0
PPARG	-0.095	0.17	-9999	-0.39	204	204
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.004	0.028	-9999	-10000	0	0
MBD3L2	-0.001	0.014	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0	0.002	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC3	-0.004	0.032	-9999	-0.29	10	10
HDAC2	0	0	-9999	-10000	0	0
YY1	0	0	-9999	-10000	0	0
HDAC8	0	0	-9999	-10000	0	0
SMAD7	0	0	-9999	-10000	0	0
NCOR2	0	0	-9999	-10000	0	0
MXD1	0	0.01	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0	0	-9999	-10000	0	0
YY1/SAP30/HDAC1	0	0.006	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.032	-9999	-10000	0	0
histone deacetylation	0.046	0.003	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.003	0.025	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GATAD2B	0	0	-9999	-10000	0	0
GATAD2A	0	0	-9999	-10000	0	0
GATA2/HDAC3	-0.017	0.081	-9999	-0.51	19	19
GATA1/HDAC1	-0.002	0.019	-9999	-10000	0	0
GATA1/HDAC3	-0.005	0.031	-9999	-10000	0	0
CHD4	0	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.011	0.074	-9999	-0.64	10	10
SIN3/HDAC complex/Mad/Max	0	0.002	-9999	-10000	0	0
NuRD Complex	0	0.002	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.023	-9999	-10000	0	0
SIN3B	0	0	-9999	-10000	0	0
MTA2	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
HDAC complex	-0.001	0.011	-9999	-10000	0	0
GATA1/Fog1	-0.003	0.021	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.016	0.098	-9999	-0.84	10	10
negative regulation of cell growth	0.045	0.004	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0	0.001	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.006	0.049	-9999	-0.45	10	10
SIN3/HDAC complex/NCoR1	0	0.007	-9999	-10000	0	0
TFCP2	0	0	-9999	-10000	0	0
NR2C1	0	0	-9999	-10000	0	0
MBD3	0	0	-9999	-10000	0	0
MBD2	0	0	-9999	-10000	0	0

×

FoxO family 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.03	0.033	-9999	-10000	0	0
PLK1	0.011	0.11	-9999	-0.6	1	1
CDKN1B	0.082	0.067	-9999	-0.55	3	3
FOXO3	0.043	0.096	-9999	-0.49	6	6
KAT2B	0.008	0.012	-9999	-10000	0	0
FOXO1/SIRT1	0.008	0.035	-9999	-0.34	6	6
CAT	0.046	0.11	-9999	-1.1	3	3
CTNNB1	0	0	-9999	-10000	0	0
AKT1	0.014	0.011	-9999	-10000	0	0
FOXO1	0.033	0.035	-9999	-0.37	6	6
MAPK10	-0.048	0.19	-9999	-0.48	137	137
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.062	0.088	-9999	-10000	0	0
response to oxidative stress	0.005	0.011	-9999	-10000	0	0
FOXO3A/SIRT1	-0.013	0.059	-9999	-0.48	5	5
XPO1	0	0	-9999	-10000	0	0
EP300	0.002	0.005	-9999	-10000	0	0
BCL2L11	0.029	0.018	-9999	-10000	0	0
FOXO1/SKP2	-0.002	0.028	-9999	-0.34	5	5
mol:GDP	0.005	0.011	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
GADD45A	0.068	0.058	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.068	0.029	-9999	-10000	0	0
MST1	-0.004	0.098	-9999	-0.84	11	11
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.001	0.044	-9999	-0.36	4	4
YWHAB	0	0	-9999	-10000	0	0
MAPK8	0.037	0.006	-9999	-10000	0	0
MAPK9	0.036	0.005	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
YWHAZ	-0.001	0.017	-9999	-0.28	3	3
SIRT1	0.002	0.007	-9999	-10000	0	0
SOD2	0.092	0.069	-9999	-10000	0	0
RBL2	0.062	0.072	-9999	-10000	0	0
RAL/GDP	0.01	0.015	-9999	-10000	0	0
CHUK	0.008	0.012	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
RAL/GTP	0.029	0.01	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
FASLG	0.013	0.14	-9999	-1.5	6	6
SKP2	0	0	-9999	-10000	0	0
USP7	0	0	-9999	-10000	0	0
IKBKB	0.007	0.018	-9999	-0.26	2	2
CCNB1	0.035	0.1	-9999	-0.6	1	1
FOXO1-3a-4/beta catenin	-0.007	0.032	-9999	-0.41	2	2
proteasomal ubiquitin-dependent protein catabolic process	-0.002	0.028	-9999	-0.34	5	5
CSNK1A1	0	0	-9999	-10000	0	0
SGK1	0.004	0.06	-9999	-0.84	4	4
CSNK1G3	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
ZFAND5	0.067	0.078	-9999	-10000	0	0
SFN	-0.016	0.11	-9999	-0.62	21	21
CDK2	0.002	0.005	-9999	-10000	0	0
FOXO3A/14-3-3	0.02	0.051	-9999	-10000	0	0
CREBBP	0.002	0.005	-9999	-10000	0	0
FBXO32	0.045	0.12	-9999	-1.4	3	3
BCL6	0.059	0.095	-9999	-1.2	2	2
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0

×

PDGFR-beta signaling pathway

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
S1P1/Sphingosine-1-phosphate	-0.004	0.041	-9999	-0.55	4	4
PDGFB-D/PDGFRB/SLAP	-0.003	0.036	-9999	-0.64	2	2
PDGFB-D/PDGFRB/APS/CBL	-0.006	0.037	-9999	-0.55	2	2
AKT1	-0.007	0.031	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.004	0.042	-9999	-0.57	4	4
PIK3CA	0	0.01	-9999	-10000	0	0
FGR	-0.003	0.029	-9999	-0.53	2	2
mol:Ca2+	0.033	0.04	-9999	-0.68	2	2
MYC	0.038	0.14	-9999	-0.83	22	22
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.002	0.024	-9999	-0.45	2	2
LRP1/PDGFRB/PDGFB	-0.007	0.072	-9999	-0.67	9	9
GRB10	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0.033	0.041	-9999	-0.69	2	2
PTEN	-0.002	0.041	-9999	-0.84	2	2
GRB2	0	0.01	-9999	-10000	0	0
GRB7	-0.021	0.077	-9999	-0.29	62	62
PDGFB-D/PDGFRB/SHP2	-0.002	0.031	-9999	-0.64	2	2
PDGFB-D/PDGFRB/GRB10	-0.002	0.031	-9999	-0.64	2	2
cell cycle arrest	-0.003	0.036	-9999	-0.64	2	2
HRAS	0	0.01	-9999	-10000	0	0
HIF1A	0.055	0.043	-9999	-10000	0	0
GAB1	0.036	0.048	-9999	-0.66	2	2
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.04	0.047	-9999	-0.61	2	2
PDGFB-D/PDGFRB	-0.003	0.032	-9999	-0.56	2	2
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.002	0.031	-9999	-0.64	2	2
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.006	0.046	-9999	-0.57	4	4
positive regulation of MAPKKK cascade	-0.002	0.031	-9999	-0.64	2	2
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	0.033	0.041	-9999	-0.7	2	2
E5	0	0.001	-9999	-10000	0	0
CSK	0	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.015	0.059	-9999	-0.64	3	3
SHB	-0.001	0.03	-9999	-0.84	1	1
BLK	-0.002	0.052	-9999	-0.63	5	5
PTPN2	0	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.002	0.031	-9999	-0.64	2	2
BCAR1	0	0	-9999	-10000	0	0
VAV2	0.04	0.057	-9999	-0.56	3	3
CBL	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.002	0.031	-9999	-0.64	2	2
LCK	-0.01	0.076	-9999	-0.61	13	13
PDGFRB	-0.002	0.041	-9999	-0.84	2	2
ACP1	0	0	-9999	-10000	0	0
HCK	-0.002	0.029	-9999	-0.53	2	2
ABL1	0.034	0.042	-9999	-0.62	2	2
PDGFB-D/PDGFRB/CBL	0.035	0.051	-9999	-0.76	2	2
PTPN1	-0.003	0.031	-9999	-0.28	11	11
SNX15	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
STAT1	-0.006	0.04	-9999	-10000	0	0
cell proliferation	0.039	0.13	-9999	-0.72	22	22
SLA	-0.003	0.027	-9999	-0.28	8	8
actin cytoskeleton reorganization	-0.002	0.027	-9999	-10000	0	0
SRC	-0.002	0.028	-9999	-0.53	2	2
PI3K	-0.009	0.035	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.012	0.048	-9999	-0.56	3	3
SH2B2	-0.01	0.052	-9999	-10000	0	0
PLCgamma1/SPHK1	-0.004	0.043	-9999	-0.6	4	4
LYN	-0.002	0.029	-9999	-0.53	2	2
LRP1	-0.009	0.086	-9999	-0.84	9	9
SOS1	0	0	-9999	-10000	0	0
STAT5B	-0.003	0.05	-9999	-0.84	3	3
STAT5A	-0.007	0.076	-9999	-0.84	7	7
NCK1-2/p130 Cas	-0.002	0.024	-9999	-0.45	2	2
SPHK1	-0.004	0.048	-9999	-0.84	2	2
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.033	0.041	-9999	-0.7	2	2
PLCG1	0.034	0.042	-9999	-0.72	2	2
NHERF/PDGFRB	-0.014	0.048	-9999	-0.55	2	2
YES1	-0.003	0.035	-9999	-0.56	3	3
cell migration	-0.014	0.047	-9999	-0.55	2	2
SHC/Grb2/SOS1	-0.002	0.024	-9999	-0.45	2	2
SLC9A3R2	0	0	-9999	-10000	0	0
SLC9A3R1	-0.027	0.082	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	-0.013	0.047	-9999	-0.51	4	4
FYN	-0.003	0.05	-9999	-0.92	2	2
DOK1	-0.001	0.028	-9999	-0.51	2	2
HRAS/GTP	0	0.006	-9999	-10000	0	0
PDGFB	0	0	-9999	-10000	0	0
RAC1	0.046	0.081	-9999	-0.43	22	22
PRKCD	0.002	0.031	-9999	-0.51	2	2
FER	-0.001	0.053	-9999	-0.52	8	8
MAPKKK cascade	-0.002	0.023	-9999	-0.44	2	2
RASA1	0.002	0.031	-9999	-0.51	2	2
NCK1	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
p62DOK/Csk	-0.002	0.025	-9999	-0.47	2	2
PDGFB-D/PDGFRB/SHB	-0.003	0.039	-9999	-0.64	3	3
chemotaxis	0.034	0.041	-9999	-0.6	2	2
STAT1-3-5/STAT1-3-5	-0.009	0.057	-9999	-0.67	2	2
Bovine Papilomavirus E5/PDGFRB	-0.002	0.032	-9999	-0.65	2	2
PTPRJ	0	0	-9999	-10000	0	0

×

Arf6 downstream pathway

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.029	0.041	-10000	0	-10000	0	0
regulation of axonogenesis	0.003	0.025	0.33	5	-10000	0	5
myoblast fusion	0.007	0.025	-10000	0	-10000	0	0
mol:GTP	-0.005	0.014	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.008	0.028	-10000	0	-10000	0	0
ARF1/GTP	-0.002	0.007	-10000	0	-10000	0	0
mol:GM1	0.006	0.013	-10000	0	-10000	0	0
mol:Choline	0.022	0.045	-10000	0	-0.55	5	5
lamellipodium assembly	-0.004	0.03	-10000	0	-10000	0	0
MAPK3	0.02	0.023	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.008	0.028	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
ARF6/GDP	-0.007	0.025	-10000	0	-10000	0	0
ARF1/GDP	-0.005	0.02	-10000	0	-10000	0	0
ARF6	0.007	0.007	-10000	0	-10000	0	0
RAB11A	-0.001	0.014	-10000	0	-0.28	2	2
TIAM1	-0.001	0.019	-10000	0	-0.28	4	4
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.02	0.023	-10000	0	-10000	0	0
actin filament bundle formation	0.005	0.02	-10000	0	-10000	0	0
KALRN	-0.01	0.067	-10000	0	-0.51	14	14
RAB11FIP3/RAB11A	0	0.009	-10000	0	-10000	0	0
RhoA/GDP	-0.005	0.02	-10000	0	-10000	0	0
NME1	-0.013	0.059	-10000	0	-0.28	41	41
Rac1/GDP	-0.005	0.02	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.005	0.014	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.004	0.03	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
liver development	-0.005	0.014	-10000	0	-10000	0	0
ARF6/GTP	-0.005	0.014	-10000	0	-10000	0	0
RhoA/GTP	-0.002	0.007	-10000	0	-10000	0	0
mol:GDP	-0.005	0.027	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	-0.001	0.007	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
PLD1	0.013	0.05	-10000	0	-0.62	5	5
RAB11FIP3	0	0	-10000	0	-10000	0	0
tube morphogenesis	-0.004	0.03	-10000	0	-10000	0	0
ruffle organization	-0.003	0.025	-10000	0	-0.33	5	5
regulation of epithelial cell migration	-0.005	0.014	-10000	0	-10000	0	0
PLD2	0.016	0.013	-10000	0	-10000	0	0
PIP5K1A	-0.003	0.025	-10000	0	-0.33	5	5
mol:Phosphatidic acid	0.022	0.045	-10000	0	-0.55	5	5
Rac1/GTP	-0.004	0.03	-10000	0	-10000	0	0

×

EPO signaling pathway

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	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.06	0.071	-9999	-10000	0	0
CRKL	0.029	0.046	-9999	-10000	0	0
mol:DAG	0	0.024	-9999	-10000	0	0
HRAS	-0.005	0.015	-9999	-10000	0	0
MAPK8	0.014	0.05	-9999	-10000	0	0
RAP1A	0.029	0.046	-9999	-10000	0	0
GAB1	0.029	0.046	-9999	-10000	0	0
MAPK14	0.014	0.05	-9999	-10000	0	0
EPO	-0.037	0.11	-9999	-0.3	9	9
PLCG1	0	0.024	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.012	0.004	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.024	0.067	-9999	-0.68	5	5
GAB1/SHC/GRB2/SOS1	-0.006	0.017	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.029	0.063	-9999	-10000	0	0
IRS2	0.006	0.12	-9999	-0.5	38	38
STAT1	0.05	0.051	-9999	-10000	0	0
STAT5B	-0.003	0.043	-9999	-0.46	3	3
cell proliferation	0.024	0.047	-9999	-10000	0	0
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.005	0.014	-9999	-10000	0	0
TEC	0.027	0.052	-9999	-0.5	2	2
SOCS3	-0.005	0.064	-9999	-0.84	5	5
STAT1 (dimer)	0.05	0.051	-9999	-10000	0	0
JAK2	0.001	0.002	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.055	0.038	-9999	-10000	0	0
EPO/EPOR	-0.029	0.063	-9999	-10000	0	0
LYN	0.002	0.005	-9999	-10000	0	0
TEC/VAV2	-0.011	0.033	-9999	-0.47	2	2
elevation of cytosolic calcium ion concentration	0.012	0.004	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.017	0.047	-9999	-10000	0	0
mol:IP3	0	0.024	-9999	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.027	0.095	-9999	-0.52	16	16
SH2B3	0.001	0.002	-9999	-10000	0	0
NFKB1	0.014	0.05	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.009	0.029	-9999	-0.32	5	5
PTPN6	0.021	0.047	-9999	-10000	0	0
TEC/VAV2/GRB2	-0.009	0.03	-9999	-0.5	1	1
EPOR	0.012	0.004	-9999	-10000	0	0
INPP5D	0	0	-9999	-10000	0	0
mol:GDP	-0.006	0.018	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
PLCG2	-0.001	0.03	-9999	-0.56	2	2
CRKL/CBL/C3G	-0.008	0.02	-9999	-10000	0	0
VAV2	0.028	0.046	-9999	-10000	0	0
CBL	0.029	0.046	-9999	-10000	0	0
SHC/Grb2/SOS1	0.006	0.026	-9999	-10000	0	0
STAT5A	-0.005	0.057	-9999	-0.5	7	7
GRB2	0	0.01	-9999	-10000	0	0
STAT5 (dimer)	0.058	0.085	-9999	-0.63	3	3
LYN/PLCgamma2	-0.001	0.023	-9999	-0.64	1	1
PTPN11	0	0	-9999	-10000	0	0
BTK	0.028	0.047	-9999	-10000	0	0
BCL2	0.041	0.18	-9999	-1	24	24

×

ceramide signaling pathway

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.045	0.045	-10000	0	-10000	0	0
BAG4	-0.003	0.03	-10000	0	-0.28	10	10
BAD	0.032	0.017	-10000	0	-10000	0	0
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.082	-10000	0	-0.84	7	7
BAX	0.032	0.017	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.015	0.012	-10000	0	-0.09	1	1
IKBKB	0.051	0.043	-10000	0	-10000	0	0
MAP2K2	0.044	0.026	-10000	0	-0.49	1	1
MAP2K1	0.044	0.026	-10000	0	-0.49	1	1
SMPD1	0.021	0.012	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.049	0.049	-10000	0	-0.42	2	2
MAP2K4	0.038	0.023	-10000	0	-0.42	1	1
protein ubiquitination	0.053	0.044	-10000	0	-10000	0	0
EnzymeConsortium:2.7.1.37	0.049	0.028	-10000	0	-0.52	1	1
response to UV	0	0	-10000	0	-0.003	1	1
RAF1	0.039	0.026	-10000	0	-0.53	1	1
CRADD	0	0	-10000	0	-10000	0	0
mol:ceramide	0.025	0.018	-10000	0	-0.13	1	1
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0	0	-10000	0	-10000	0	0
MAP3K1	0.032	0.017	-10000	0	-10000	0	0
TRADD	0	0	-10000	0	-10000	0	0
RELA/p50	0	0	-10000	0	-10000	0	0
MAPK3	0.046	0.025	-10000	0	-0.48	1	1
MAPK1	0.046	0.025	-10000	0	-0.48	1	1
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.043	0.05	-10000	0	-0.44	2	2
KSR1	0.032	0.027	-10000	0	-0.56	1	1
MAPK8	0.044	0.022	-10000	0	-0.38	1	1
TRAF2	0	0.001	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-0.002	1	1
CHUK	0.052	0.043	-10000	0	-10000	0	0
TNF R/SODD	-0.002	0.019	-10000	0	-10000	0	0
TNF	-0.016	0.098	-10000	0	-0.84	10	10
CYCS	0.037	0.024	0.15	22	-10000	0	22
IKBKG	0.052	0.043	-10000	0	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.038	0.047	-10000	0	-0.34	7	7
RELA	0	0	-10000	0	-10000	0	0
RIPK1	0	0.001	-10000	0	-10000	0	0
AIFM1	0.037	0.024	0.15	22	-10000	0	22
TNF/TNF R/SODD	-0.011	0.064	-10000	0	-0.56	10	10
TNFRSF1A	0	0.001	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-0.002	1	1
CASP8	0.027	0.013	-10000	0	-10000	0	0
NSMAF	0.045	0.045	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-0.003	1	1
BCL2	-0.024	0.14	-10000	0	-0.84	24	24

×

Atypical NF-kappaB 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
BCL3/RelA	0	0.006	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.001	0.02	-9999	-0.56	1	1
NF kappa B1 p50/RelA/I kappa B alpha	-0.003	0.026	-9999	-10000	0	0
NFKBIA	0.024	0.036	-9999	-0.28	11	11
MAPK14	0	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0	0.007	-9999	-10000	0	0
ARRB2	0	0	-9999	-10000	0	0
REL	-0.001	0.029	-9999	-0.84	1	1
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0	0.008	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0	0.006	-9999	-10000	0	0
PIK3CA	0	0.01	-9999	-10000	0	0
NF kappa B1 p50 dimer	0	0.009	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
NFKB1	0.022	0.01	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	-0.004	0.031	-9999	-0.28	11	11
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.003	0.025	-9999	-10000	0	0
SRC	0	0.01	-9999	-10000	0	0
PI3K	0	0.006	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.004	0.032	-9999	-0.28	11	11
IKBKB	-0.001	0.014	-9999	-0.28	2	2
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
SYK	0	0.01	-9999	-10000	0	0
I kappa B alpha/PIK3R1	-0.004	0.029	-9999	-10000	0	0
cell death	-0.003	0.024	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.001	0.02	-9999	-0.56	1	1
LCK	-0.019	0.1	-9999	-0.46	34	34
BCL3	0	0.01	-9999	-0.28	1	1

×

Canonical NF-kappaB pathway

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	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.076	0.036	-9999	-10000	0	0
ERC1	0	0	-9999	-10000	0	0
RIP2/NOD2	-0.006	0.033	-9999	-0.35	1	1
NFKBIA	0.047	0	-9999	-10000	0	0
BIRC2	0	0	-9999	-10000	0	0
IKBKB	-0.001	0.014	-9999	-0.28	2	2
RIPK2	-0.001	0.019	-9999	-0.28	4	4
IKBKG	0	0.001	-9999	-10000	0	0
IKK complex/A20	-0.003	0.046	-9999	-10000	0	0
NEMO/A20/RIP2	-0.001	0.019	-9999	-0.28	4	4
XPO1	0	0	-9999	-10000	0	0
NEMO/ATM	0	0.002	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	0	0.004	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.008	0.046	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
MALT1	0	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
TNF/TNFR1A	-0.011	0.074	-9999	-0.64	10	10
TRAF6	0	0	-9999	-10000	0	0
PRKCA	-0.022	0.13	-9999	-0.77	24	24
CHUK	0	0	-9999	-10000	0	0
UBE2D3	0	0	-9999	-10000	0	0
TNF	-0.016	0.098	-9999	-0.84	10	10
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.047	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
IKK complex	0.001	0.005	-9999	-10000	0	0
CYLD	0	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.01	0.063	-9999	-0.4	21	21

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	-0.003	0.026	-9999	-0.43	2	2
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.003	0.03	-9999	-10000	0	0
alpha4/beta7 Integrin/MAdCAM1	-0.009	0.042	-9999	-0.45	4	4
EPO	-0.048	0.1	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.007	0.046	-9999	-0.45	6	6
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.002	0.019	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.03	0.066	-9999	-10000	0	0
lamellipodium assembly	0.001	0.006	-9999	-10000	0	0
PIK3CA	0	0.01	-9999	-10000	0	0
PI3K	0	0.006	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
JAK2	-0.009	0.018	-9999	-10000	0	0
PXN	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
MADCAM1	-0.01	0.052	-9999	-10000	0	0
cell adhesion	-0.009	0.042	-9999	-0.44	4	4
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
SRC	-0.006	0.045	-9999	-0.51	6	6
ITGB7	-0.007	0.055	-9999	-0.34	17	17
RAC1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.007	0.05	-9999	-0.56	6	6
p130Cas/Crk/Dock1	-0.004	0.036	-9999	-10000	0	0
VCAM1	-0.008	0.074	-9999	-0.56	12	12
RHOA	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.002	0.014	-9999	-10000	0	0
BCAR1	0.035	0.047	-9999	-0.47	6	6
EPOR	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
GIT1	-0.001	0.019	-9999	-10000	0	0
Rac1/GTP	0.001	0.006	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0.003	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.003	0.03	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.007	0.046	-9999	-0.45	6	6
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.002	0.015	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	-0.005	0.034	-9999	-0.51	2	2
lamellipodium assembly	0.001	0.006	-9999	-10000	0	0
PIK3CA	0	0.01	-9999	-10000	0	0
PI3K	0	0.006	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
TLN1	0	0	-9999	-10000	0	0
PXN	0.022	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
ARF6/GTP	-0.001	0.01	-9999	-10000	0	0
cell adhesion	-0.001	0.01	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.001	0.012	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.007	0.055	-9999	-0.34	17	17
ARF6/GDP	0	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.005	0.042	-9999	-0.48	6	6
p130Cas/Crk/Dock1	0	0	-9999	-10000	0	0
VCAM1	-0.008	0.074	-9999	-0.56	12	12
alpha4/beta1 Integrin/Paxillin/Talin	-0.001	0.01	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.002	0.012	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
mol:GDP	0.002	0.012	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GIT1	-0.001	0.019	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.001	0.01	-9999	-10000	0	0
Rac1/GTP	0.001	0.007	-9999	-10000	0	0

×

PLK2 and PLK4 events

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
PLK2	0	0	-9999	-9999
PLK4	-0.014	0.06	-9999	-9999
regulation of centriole replication	0.012	0.042	-9999	-9999

×

Sumoylation by RanBP2 regulates transcriptional repression

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	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.014	-9999	-0.4	1	1
MDM2/SUMO1	0	0.007	-9999	-10000	0	0
HDAC4	-0.001	0.029	-9999	-0.84	1	1
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
SUMO1	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.028	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
SUMO1/HDAC4	-0.001	0.016	-9999	-0.47	1	1
SUMO1/HDAC1	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	-0.001	0.008	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0	0	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	-0.001	0.019	-9999	-0.28	4	4
UBE2I	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
PIAS2	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Arf1 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	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
coatomer protein complex	0	0.004	-9999	-9999
EntrezGene:79658	0	0	-9999	-9999
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.02	0	-9999	-9999
AP2	0	0	-9999	-9999
mol:DAG	0	0	-9999	-9999
Arfaptin 2/Rac/GTP	0	0	-9999	-9999
CLTB	0	0.01	-9999	-9999
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0.001	-9999	-9999
CD4	0	0	-9999	-9999
CLTA	0	0	-9999	-9999
mol:GTP	0.002	0	-9999	-9999
ARFGAP1	0.011	0.01	-9999	-9999
mol:PI-4-5-P2	0	0	-9999	-9999
ARF1/GTP	0	0	-9999	-9999
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0	0.004	-9999	-9999
mol:Choline	0	0	-9999	-9999
mol:GDP	0	0	-9999	-9999
ARF1	0	0	-9999	-9999
DDEF1	0	0	-9999	-9999
ARF1/GDP	0	0.005	-9999	-9999
AP2M1	0	0	-9999	-9999
EntrezGene:1313	0	0	-9999	-9999
actin filament polymerization	0	0	-9999	-9999
Rac/GTP	0	0	-9999	-9999
ARF1/GTP/GGA3/ARF-GAP1	0	0.005	-9999	-9999
ARFIP2	0	0	-9999	-9999
COPA	0	0	-9999	-9999
RAC1	0	0	-9999	-9999
ARF1/GTP/coatomer protein complex	0.025	0.001	-9999	-9999
ARF1/GTP/ARHGAP10	0	0	-9999	-9999
GGA3	0	0	-9999	-9999
ARF1/GTP/Membrin	0	0	-9999	-9999
AP2A1	0	0	-9999	-9999
coatomer protein complex/ARF1/GTP/ARF-GAP1	0	0.002	-9999	-9999
ARF1/GDP/Membrin	0	0	-9999	-9999
Arfaptin 2/Rac/GDP	0	0	-9999	-9999
CYTH2	0	0	-9999	-9999
ARF1/GTP/GGA3	0	0	-9999	-9999
mol:ATP	0	0	-9999	-9999
Rac/GDP	0	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	0	-9999	-9999
PLD2	0	0	-9999	-9999
ARF-GAP1/v-SNARE	0.011	0.01	-9999	-9999
PIP5K1A	0	0	-9999	-9999
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-9999
mol:Phosphatic acid	0	0	-9999	-9999
mol:Phosphatidic acid	0	0	-9999	-9999
KDEL Receptor/Ligand/ARF-GAP1	0.011	0.01	-9999	-9999
GOSR2	0	0	-9999	-9999
USO1	0	0	-9999	-9999
GBF1	0	0	-9999	-9999
ARF1/GTP/Arfaptin 2	0	0	-9999	-9999
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0	0	-9999	-9999

×

Alternative NF-kappaB pathway

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
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.001	0.007	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAP3K14	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.001	0.013	-9999	-10000	0	0
RELB	-0.002	0.021	-9999	-0.28	5	5
NFKB2	0	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	-0.001	0.011	-9999	-10000	0	0
regulation of B cell activation	-0.001	0.011	-9999	-10000	0	0

pid_entity	TCGA.HN.A2NL	TCGA.GM.A3NY	TCGA.GM.A2DO	TCGA.GM.A2DN
109_MAP3K5	0.053	0.053	0.043	0.053
47_PPARGC1A	-0.28	0	0	0
105_BMP4	-0.84	0	-0.84	0
105_BMP6	0	0	0	0
105_BMP7	0	0	0	0
105_BMP2	0	0	0	0
131_RELN/VLDLR	0	-1	-0.51	-0.51
30_TGFB1/TGF beta receptor Type II	0.015	0	0	0
84_STAT5B	-0.013	-0.076	-0.16	0.019
84_STAT5A	-0.013	-0.076	-0.16	0.019