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	248
Signaling events mediated by Stem cell factor receptor (c-Kit)	235
Reelin signaling pathway	212
EGFR-dependent Endothelin signaling events	204
Signaling mediated by p38-alpha and p38-beta	201
HIF-1-alpha transcription factor network	178
p75(NTR)-mediated signaling	145
Glucocorticoid receptor regulatory network	144
IL4-mediated signaling events	142
FOXA2 and FOXA3 transcription factor networks	139

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
Class IB PI3K non-lipid kinase events	0.2713	248	744	3	-0.22	-1000	1000	-1000	-0.022	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.2571	235	18337	78	-0.62	0.19	1000	-1000	-0.1	-1000
Reelin signaling pathway	0.2319	212	11915	56	-0.51	0	1000	-1000	-0.095	-1000
EGFR-dependent Endothelin signaling events	0.2232	204	4297	21	-0.35	0	1000	-1000	-0.062	-1000
Signaling mediated by p38-alpha and p38-beta	0.2199	201	8858	44	-0.4	0	1000	-1000	-0.045	-1000
HIF-1-alpha transcription factor network	0.1947	178	13539	76	-0.78	0.018	1000	-1000	-0.083	-1000
p75(NTR)-mediated signaling	0.1586	145	18242	125	-0.42	0	1000	-1000	-0.098	-1000
Glucocorticoid receptor regulatory network	0.1575	144	16440	114	-0.96	0.36	1000	-1000	-0.064	-1000
IL4-mediated signaling events	0.1554	142	12943	91	-1	0.51	1000	-1000	-0.11	-1000
FOXA2 and FOXA3 transcription factor networks	0.1521	139	6422	46	-1.2	0.025	1000	-1000	-0.042	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1411	129	8839	68	-0.53	0.17	1000	-1000	-0.097	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1346	123	6683	54	-0.51	0.022	1000	-1000	-0.084	-1000
Arf6 signaling events	0.1247	114	7095	62	-0.35	0.017	1000	-1000	-0.055	-1000
ErbB2/ErbB3 signaling events	0.1236	113	7382	65	-0.42	0.018	1000	-1000	-0.06	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1225	112	9929	88	-0.36	0.036	1000	-1000	-0.11	-1000
Endothelins	0.1214	111	10681	96	-0.39	0.034	1000	-1000	-0.072	-1000
EPHB forward signaling	0.1214	111	9439	85	-0.35	0.19	1000	-1000	-0.085	-1000
Wnt signaling	0.1204	110	773	7	-0.19	-0.006	1000	-1000	-0.05	-1000
Ephrin B reverse signaling	0.1171	107	5175	48	-0.35	0.2	1000	-1000	-0.073	-1000
FOXM1 transcription factor network	0.1171	107	5486	51	-0.44	0.013	1000	-1000	-0.14	-1000
IGF1 pathway	0.1160	106	6070	57	-0.18	0.079	1000	-1000	-0.08	-1000
IL23-mediated signaling events	0.0985	90	5410	60	-0.47	0.017	1000	-1000	-0.12	-1000
BMP receptor signaling	0.0952	87	7085	81	-0.57	0.025	1000	-1000	-0.087	-1000
Calcium signaling in the CD4+ TCR pathway	0.0930	85	2640	31	-0.35	0.011	1000	-1000	-0.096	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0930	85	10287	120	-0.63	0.25	1000	-1000	-0.077	-1000
ErbB4 signaling events	0.0919	84	5861	69	-0.44	0.061	1000	-1000	-0.082	-1000
Aurora B signaling	0.0919	84	5628	67	-0.33	0.012	1000	-1000	-0.074	-1000
Visual signal transduction: Rods	0.0897	82	4306	52	-0.52	0	1000	-1000	-0.075	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0886	81	6960	85	-0.26	0.011	1000	-1000	-0.066	-1000
Nongenotropic Androgen signaling	0.0886	81	4251	52	-0.24	0.11	1000	-1000	-0.058	-1000
Noncanonical Wnt signaling pathway	0.0875	80	2097	26	-0.19	0	1000	-1000	-0.075	-1000
Syndecan-1-mediated signaling events	0.0864	79	2719	34	-0.21	0	1000	-1000	-0.067	-1000
Glypican 1 network	0.0864	79	3811	48	-0.33	0.03	1000	-1000	-0.052	-1000
Signaling events regulated by Ret tyrosine kinase	0.0864	79	6519	82	-0.17	0	1000	-1000	-0.079	-1000
Aurora C signaling	0.0853	78	546	7	-0.16	0	1000	-1000	-0.042	-1000
Plasma membrane estrogen receptor signaling	0.0810	74	6399	86	-0.2	0.085	1000	-1000	-0.076	-1000
IL6-mediated signaling events	0.0755	69	5189	75	-0.3	0.053	1000	-1000	-0.074	-1000
amb2 Integrin signaling	0.0744	68	5645	82	-0.53	0	1000	-1000	-0.08	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0722	66	3465	52	-0.2	0.031	1000	-1000	-0.064	-1000
Integrins in angiogenesis	0.0722	66	5571	84	-0.34	0	1000	-1000	-0.089	-1000
Signaling events mediated by PTP1B	0.0700	64	4917	76	-0.67	0.068	1000	-1000	-0.071	-1000
Ephrin A reverse signaling	0.0689	63	445	7	-0.081	0	1000	-1000	-0.044	-1000
Syndecan-3-mediated signaling events	0.0656	60	2120	35	-0.36	0	1000	-1000	-0.061	-1000
LPA receptor mediated events	0.0656	60	6191	102	-0.3	0.029	1000	-1000	-0.079	-1000
Fc-epsilon receptor I signaling in mast cells	0.0646	59	5777	97	-0.26	0.028	1000	-1000	-0.078	-1000
Signaling events mediated by the Hedgehog family	0.0613	56	2917	52	-0.22	0.03	1000	-1000	-0.076	-1000
PDGFR-alpha signaling pathway	0.0580	53	2364	44	-0.38	0.019	1000	-1000	-0.055	-1000
S1P1 pathway	0.0580	53	1929	36	-0.33	0.007	1000	-1000	-0.066	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0558	51	1760	34	-0.081	0	1000	-1000	-0.062	-1000
E-cadherin signaling in keratinocytes	0.0558	51	2219	43	-0.3	0.043	1000	-1000	-0.067	-1000
Visual signal transduction: Cones	0.0547	50	1906	38	-0.18	0.006	1000	-1000	-0.056	-1000
TCGA08_rtk_signaling	0.0536	49	1290	26	-0.3	0.027	1000	-1000	-0.028	-1000
Signaling events mediated by PRL	0.0536	49	1690	34	-0.19	0.02	1000	-1000	-0.061	-1000
Presenilin action in Notch and Wnt signaling	0.0514	47	2890	61	-0.44	0.013	1000	-1000	-0.06	-1000
Ras signaling in the CD4+ TCR pathway	0.0503	46	798	17	-0.12	0	1000	-1000	-0.055	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0481	44	3321	74	-0.3	0.07	1000	-1000	-0.092	-1000
Signaling events mediated by HDAC Class III	0.0470	43	1741	40	-0.59	0.029	1000	-1000	-0.046	-1000
Rapid glucocorticoid signaling	0.0470	43	860	20	-0.19	0.027	1000	-1000	-0.042	-1000
FAS signaling pathway (CD95)	0.0460	42	1998	47	-0.48	0.012	1000	-1000	-0.047	-1000
LPA4-mediated signaling events	0.0449	41	492	12	-0.16	0.019	1000	-1000	-0.015	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0438	40	1349	33	-0.57	0	1000	-1000	-0.073	-1000
Nectin adhesion pathway	0.0427	39	2487	63	-0.077	0.008	1000	-1000	-0.076	-1000
Canonical Wnt signaling pathway	0.0416	38	1950	51	-0.44	0.15	1000	-1000	-0.059	-1000
Glypican 2 network	0.0372	34	137	4	-0.034	-0.028	1000	-1000	-0.038	-1000
IL27-mediated signaling events	0.0372	34	1756	51	-0.3	0.023	1000	-1000	-0.079	-1000
IL12-mediated signaling events	0.0361	33	2871	87	-0.37	0.053	1000	-1000	-0.11	-1000
TCR signaling in naïve CD8+ T cells	0.0361	33	3151	93	-0.17	0.082	1000	-1000	-0.075	-1000
Insulin Pathway	0.0350	32	2437	74	-0.2	0.032	1000	-1000	-0.079	-1000
Regulation of Telomerase	0.0328	30	3110	102	-0.35	0.021	1000	-1000	-0.09	-1000
Syndecan-4-mediated signaling events	0.0328	30	2010	67	-0.33	0.005	1000	-1000	-0.081	-1000
Coregulation of Androgen receptor activity	0.0317	29	2235	76	-0.2	0.035	1000	-1000	-0.051	-1000
PLK1 signaling events	0.0306	28	2438	85	-0.22	0.034	1000	-1000	-0.062	-1000
BCR signaling pathway	0.0295	27	2677	99	-0.14	0.042	1000	-1000	-0.08	-1000
Regulation of Androgen receptor activity	0.0295	27	1911	70	-0.27	0.021	1000	-1000	-0.068	-1000
Regulation of nuclear SMAD2/3 signaling	0.0274	25	3510	136	-0.33	0.051	1000	-1000	-0.079	-1000
Thromboxane A2 receptor signaling	0.0274	25	2682	105	-0.3	0.069	1000	-1000	-0.07	-1000
Regulation of p38-alpha and p38-beta	0.0274	25	1364	54	-0.38	0.027	1000	-1000	-0.072	-1000
Effects of Botulinum toxin	0.0274	25	672	26	-0.1	0	1000	-1000	-0.052	-1000
Osteopontin-mediated events	0.0263	24	931	38	-0.26	0.027	1000	-1000	-0.098	-1000
Arf6 trafficking events	0.0263	24	1757	71	-0.46	0.032	1000	-1000	-0.068	-1000
Syndecan-2-mediated signaling events	0.0230	21	1503	69	-0.2	0.035	1000	-1000	-0.061	-1000
E-cadherin signaling events	0.0186	17	86	5	-0.025	0	1000	-1000	-0.049	-1000
Hedgehog signaling events mediated by Gli proteins	0.0175	16	1083	65	-0.069	0.041	1000	-1000	-0.071	-1000
Class I PI3K signaling events mediated by Akt	0.0175	16	1093	68	-0.27	0.053	1000	-1000	-0.069	-1000
Ceramide signaling pathway	0.0164	15	1161	76	-0.18	0.047	1000	-1000	-0.061	-1000
TRAIL signaling pathway	0.0164	15	745	48	-0.079	0.046	1000	-1000	-0.066	-1000
Signaling mediated by p38-gamma and p38-delta	0.0153	14	217	15	-0.017	0.021	1000	-1000	-0.055	-1000
Caspase cascade in apoptosis	0.0142	13	1019	74	-0.052	0.045	1000	-1000	-0.063	-1000
PLK2 and PLK4 events	0.0142	13	40	3	-0.012	0.013	1000	-1000	-0.022	-1000
Cellular roles of Anthrax toxin	0.0131	12	497	39	-0.14	0.02	1000	-1000	-0.039	-1000
Aurora A signaling	0.0131	12	760	60	-0.2	0.006	1000	-1000	-0.066	-1000
Retinoic acid receptors-mediated signaling	0.0131	12	747	58	-0.11	0.038	1000	-1000	-0.068	-1000
S1P4 pathway	0.0131	12	301	25	-0.042	0	1000	-1000	-0.051	-1000
S1P5 pathway	0.0109	10	181	17	-0.042	0.024	1000	-1000	-0.049	-1000
E-cadherin signaling in the nascent adherens junction	0.0109	10	813	76	-0.025	0.047	1000	-1000	-0.077	-1000
S1P3 pathway	0.0109	10	452	42	-0.032	0.021	1000	-1000	-0.054	-1000
IL1-mediated signaling events	0.0098	9	595	62	-0.038	0.031	1000	-1000	-0.091	-1000
BARD1 signaling events	0.0088	8	488	57	-0.11	0.022	1000	-1000	-0.073	-1000
JNK signaling in the CD4+ TCR pathway	0.0088	8	145	17	-0.019	0.044	1000	-1000	-0.067	-1000
IL2 signaling events mediated by PI3K	0.0088	8	510	58	-0.038	0.064	1000	-1000	-0.068	-1000
Signaling events mediated by HDAC Class II	0.0077	7	552	75	-0.15	0	1000	-1000	-0.063	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0077	7	208	28	-0.042	0.018	1000	-1000	-0.054	-1000
mTOR signaling pathway	0.0077	7	397	53	-0.017	0.027	1000	-1000	-0.056	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0077	7	634	83	-0.071	0.05	1000	-1000	-0.079	-1000
IL2 signaling events mediated by STAT5	0.0077	7	156	22	-0.12	0.066	1000	-1000	-0.041	-1000
TCGA08_retinoblastoma	0.0077	7	57	8	-0.047	0.009	1000	-1000	-0.028	-1000
VEGFR1 specific signals	0.0066	6	377	56	-0.17	0.062	1000	-1000	-0.07	-1000
p38 MAPK signaling pathway	0.0066	6	288	44	-0.074	0.029	1000	-1000	-0.063	-1000
a4b1 and a4b7 Integrin signaling	0.0055	5	29	5	-0.008	-0.002	1000	-1000	-0.036	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0055	5	252	45	-0.026	0.074	1000	-1000	-0.075	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0055	5	638	125	-0.17	0.086	1000	-1000	-0.086	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0044	4	114	23	-0.03	0.041	1000	-1000	-0.074	-1000
HIF-2-alpha transcription factor network	0.0044	4	196	43	-0.16	0.18	1000	-1000	-0.073	-1000
Signaling events mediated by HDAC Class I	0.0044	4	418	104	-0.094	0.045	1000	-1000	-0.065	-1000
PDGFR-beta signaling pathway	0.0044	4	406	97	-0.024	0.055	1000	-1000	-0.076	-1000
EPO signaling pathway	0.0033	3	175	55	-0.036	0.057	1000	-1000	-0.084	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0033	3	115	37	-0.047	0.035	1000	-1000	-0.075	-1000
ceramide signaling pathway	0.0033	3	151	49	-0.027	0.052	1000	-1000	-0.051	-1000
FoxO family signaling	0.0033	3	247	64	-0.044	0.093	1000	-1000	-0.073	-1000
Atypical NF-kappaB pathway	0.0033	3	93	31	-0.018	0.024	1000	-1000	-0.064	-1000
Canonical NF-kappaB pathway	0.0022	2	90	39	-0.02	0.076	1000	-1000	-0.074	-1000
Circadian rhythm pathway	0.0022	2	47	22	-0.018	0.044	1000	-1000	-0.061	-1000
Insulin-mediated glucose transport	0.0022	2	77	32	-0.14	0.031	1000	-1000	-0.057	-1000
IFN-gamma pathway	0.0022	2	194	68	-0.074	0.075	1000	-1000	-0.084	-1000
Class I PI3K signaling events	0.0022	2	214	73	-0.039	0.06	1000	-1000	-0.069	-1000
Arf6 downstream pathway	0.0011	1	54	43	-0.014	0.022	1000	-1000	-0.042	-1000
Paxillin-dependent events mediated by a4b1	0.0011	1	59	36	-0.008	0.022	1000	-1000	-0.067	-1000
TCGA08_p53	0.0000	0	0	7	-0.021	0.015	1000	-1000	-0.024	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	3	27	-0.001	0.028	1000	-1000	-0.057	-1000
Arf1 pathway	0.0000	0	0	54	-0.001	0.025	1000	-1000	-0.043	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	-0.002	0	1000	-1000	-0.059	-1000
Total	NA	6577	391415	7203	-32	-990	131000	-131000	-8.8	-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	0.22	0.37	0.82	248	-10000	0	248
PI3K Class IB/PDE3B	-0.22	0.37	-10000	0	-0.82	248	248
PDE3B	-0.22	0.37	-10000	0	-0.82	248	248

×

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	416	416
CRKL	-0.17	0.23	-10000	0	-0.41	415	415
HRAS	-0.16	0.17	-10000	0	-0.55	25	25
mol:PIP3	-0.17	0.21	-10000	0	-0.4	416	416
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	417	417
FOXO3	-0.15	0.21	-10000	0	-0.38	415	415
AKT1	-0.16	0.22	-10000	0	-0.41	416	416
BAD	-0.15	0.21	-10000	0	-0.37	415	415
megakaryocyte differentiation	-0.18	0.24	-10000	0	-0.43	417	417
GSK3B	-0.15	0.21	-10000	0	-0.37	415	415
RAF1	-0.091	0.17	-10000	0	-0.46	19	19
SHC1	0	0	-10000	0	-10000	0	0
STAT3	-0.18	0.24	-10000	0	-0.44	417	417
STAT1	-0.45	0.56	-10000	0	-1.1	423	423
HRAS/SPRED1	-0.13	0.14	-10000	0	-0.44	22	22
cell proliferation	-0.18	0.24	-10000	0	-0.44	417	417
PIK3CA	0	0.009	-10000	0	-10000	0	0
TEC	-0.002	0.039	-10000	0	-0.82	2	2
RPS6KB1	-0.18	0.24	-10000	0	-0.44	417	417
HRAS/SPRED2	-0.13	0.14	-10000	0	-0.44	22	22
LYN/TEC/p62DOK	-0.19	0.2	-10000	0	-0.4	416	416
MAPK3	-0.054	0.13	-10000	0	-0.32	17	17
STAP1	-0.2	0.24	-10000	0	-0.45	419	419
GRAP2	-0.014	0.1	-10000	0	-0.82	14	14
JAK2	-0.4	0.44	-10000	0	-0.88	419	419
STAT1 (dimer)	-0.44	0.55	-10000	0	-1	423	423
mol:Gleevec	0.006	0.009	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.19	0.2	-10000	0	-0.41	416	416
actin filament polymerization	-0.18	0.24	-10000	0	-0.44	417	417
LYN	0	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.27	0.33	-10000	0	-0.62	417	417
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
CBL/CRKL/GRB2	-0.17	0.18	-10000	0	-0.42	25	25
PI3K	-0.19	0.2	-10000	0	-0.41	416	416
PTEN	-0.002	0.039	-10000	0	-0.82	2	2
SCF/KIT/EPO/EPOR	-0.6	0.68	-10000	0	-1.3	415	415
MAPK8	-0.18	0.24	-10000	0	-0.44	417	417
STAT3 (dimer)	-0.18	0.24	-10000	0	-0.43	417	417
positive regulation of transcription	-0.041	0.11	-10000	0	-0.26	17	17
mol:GDP	-0.16	0.18	-10000	0	-0.59	25	25
PIK3C2B	-0.18	0.24	-10000	0	-0.44	417	417
CBL/CRKL	-0.17	0.19	-10000	0	-0.38	415	415
FER	-0.18	0.24	-10000	0	-0.44	420	420
SH2B3	-0.18	0.24	-10000	0	-0.44	417	417
PDPK1	-0.15	0.2	-10000	0	-0.36	415	415
SNAI2	-0.19	0.24	-10000	0	-0.45	418	418
positive regulation of cell proliferation	-0.32	0.41	-10000	0	-0.75	423	423
KITLG	0	0.075	-10000	0	-0.85	6	6
cell motility	-0.32	0.41	-10000	0	-0.75	423	423
PTPN6	0.015	0.021	-10000	0	-0.27	2	2
EPOR	-0.097	0.16	-10000	0	-10000	0	0
STAT5A (dimer)	-0.26	0.34	-10000	0	-0.62	419	419
SOCS1	-0.003	0.038	-10000	0	-0.34	9	9
cell migration	0.19	0.24	0.45	424	-10000	0	424
SOS1	0	0	-10000	0	-10000	0	0
EPO	-0.044	0.11	-10000	0	-0.3	94	94
VAV1	-0.002	0.03	-10000	0	-0.46	3	3
GRB10	-0.18	0.24	-10000	0	-0.44	417	417
PTPN11	0.012	0.013	-10000	0	-10000	0	0
SCF/KIT	-0.22	0.24	-10000	0	-0.47	417	417
GO:0007205	0.009	0.013	-10000	0	-10000	0	0
MAP2K1	-0.063	0.14	-10000	0	-0.36	17	17
CBL	0	0	-10000	0	-10000	0	0
KIT	-0.62	0.74	-10000	0	-1.4	413	413
MAP2K2	-0.063	0.14	-10000	0	-0.36	17	17
SHC/Grb2/SOS1	-0.19	0.2	-10000	0	-0.4	415	415
STAT5A	-0.27	0.35	-10000	0	-0.65	417	417
GRB2	0	0.009	-10000	0	-10000	0	0
response to radiation	-0.18	0.24	-10000	0	-0.44	418	418
SHC/GRAP2	-0.01	0.078	-10000	0	-0.63	14	14
PTPRO	-0.18	0.24	-10000	0	-0.44	417	417
SH2B2	-0.19	0.24	-10000	0	-0.45	417	417
DOK1	0	0.009	-10000	0	-10000	0	0
MATK	-0.19	0.25	-10000	0	-0.46	424	424
CREBBP	0.019	0.018	-10000	0	-10000	0	0
BCL2	-0.13	0.3	-10000	0	-1.6	30	30

×

Reelin signaling pathway

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
CDK5R1/CDK5	-0.006	0.033	-9999	-10000	0	0
VLDLR	-0.023	0.14	-9999	-0.82	25	25
CRKL	0	0	-9999	-10000	0	0
LRPAP1	0	0	-9999	-10000	0	0
FYN	-0.001	0.027	-9999	-0.82	1	1
ITGA3	-0.004	0.056	-9999	-0.82	4	4
RELN/VLDLR/Fyn	-0.35	0.28	-9999	-0.56	570	570
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.004	0.038	-9999	-0.47	6	6
AKT1	-0.21	0.17	-9999	-0.33	570	570
MAP2K7	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
DAB1	-0.017	0.067	-9999	-0.28	56	56
RELN/LRP8/DAB1	-0.34	0.26	-9999	-0.53	565	565
LRPAP1/LRP8	-0.02	0.056	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.32	0.24	-9999	-0.5	565	565
DAB1/alpha3/beta1 Integrin	-0.29	0.23	-9999	-0.46	573	573
long-term memory	-0.38	0.31	-9999	-0.56	610	610
DAB1/LIS1	-0.3	0.24	-9999	-0.48	570	570
DAB1/CRLK/C3G	-0.29	0.23	-9999	-0.52	223	223
PIK3CA	0	0.009	-9999	-10000	0	0
DAB1/NCK2	-0.31	0.24	-9999	-0.48	570	570
ARHGEF2	0	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.092	0.26	-9999	-0.77	109	109
CDK5R1	-0.009	0.048	-9999	-0.28	28	28
RELN	-0.51	0.4	-9999	-0.82	564	564
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
RELN/LRP8/Fyn	-0.35	0.27	-9999	-0.57	564	564
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.36	0.3	-9999	-0.56	577	577
MAPK8	-0.003	0.047	-9999	-0.82	3	3
RELN/VLDLR/DAB1	-0.34	0.27	-9999	-0.53	570	570
ITGB1	0	0	-9999	-10000	0	0
MAP1B	-0.33	0.26	-9999	-0.52	572	572
RELN/LRP8	-0.35	0.27	-9999	-0.57	564	564
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.35	0.26	-9999	-0.53	598	598
PI3K	-0.001	0.022	-9999	-0.63	1	1
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.003	0.043	-9999	-0.63	4	4
RAP1A	-0.27	0.21	-9999	-0.55	128	128
PAFAH1B1	0	0	-9999	-10000	0	0
MAPK8IP1	-0.004	0.051	-9999	-0.48	8	8
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.066	0.22	-9999	-0.81	74	74
NCK2	0	0	-9999	-10000	0	0
neuron differentiation	-0.14	0.11	-9999	-0.42	8	8
neuron adhesion	-0.25	0.2	-9999	-0.52	130	130
LRP8	-0.032	0.089	-9999	-0.28	105	105
GSK3B	-0.18	0.18	-9999	-0.61	20	20
RELN/VLDLR/DAB1/Fyn	-0.31	0.25	-9999	-0.5	570	570
MAP3K11	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.22	0.18	-9999	-0.36	570	570
CDK5	-0.002	0.021	-9999	-10000	0	0
MAPT	-0.043	0.25	-9999	-0.75	96	96
neuron migration	-0.24	0.24	-9999	-0.42	565	565
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.14	0.11	-9999	-0.43	8	8
RELN/VLDLR	-0.34	0.26	-9999	-0.53	570	570

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	-0.001	0.013	-9999	-0.28	2	2
EGFR	-0.3	0.4	-9999	-0.82	331	331
EGF/EGFR	-0.29	0.32	-9999	-0.57	463	463
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.26	0.28	-9999	-0.52	453	453
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	-0.16	0.33	-9999	-0.82	183	183
EGF/EGFR dimer/SHC	-0.3	0.32	-9999	-0.61	453	453
mol:GDP	-0.26	0.28	-9999	-0.52	453	453
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.066	0.22	-9999	-0.82	74	74
GRB2/SOS1	0	0.006	-9999	-10000	0	0
HRAS/GTP	-0.24	0.26	-9999	-0.48	453	453
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.24	0.26	-9999	-0.48	453	453
FRAP1	-0.25	0.27	-9999	-0.5	453	453
EGF/EGFR dimer	-0.35	0.37	-9999	-0.7	453	453
SOS1	0	0	-9999	-10000	0	0
GRB2	0	0.009	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.051	0.17	-9999	-0.63	73	73

×

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	0.63	-9999	-1.3	309	309
MKNK1	0	0	-9999	-10000	0	0
MAPK14	-0.082	0.15	-9999	-0.38	15	15
ATF2/c-Jun	-0.056	0.16	-9999	-0.91	14	14
MAPK11	-0.084	0.16	-9999	-0.3	311	311
MITF	-0.093	0.2	-9999	-0.36	314	314
MAPKAPK5	-0.09	0.19	-9999	-0.35	311	311
KRT8	-0.096	0.19	-9999	-0.36	312	312
MAPKAPK3	0	0	-9999	-10000	0	0
MAPKAPK2	0	0.009	-9999	-10000	0	0
p38alpha-beta/CK2	-0.13	0.24	-9999	-0.45	311	311
CEBPB	-0.09	0.19	-9999	-0.35	311	311
SLC9A1	-0.09	0.19	-9999	-0.35	311	311
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.083	0.19	-9999	-0.34	311	311
p38alpha-beta/MNK1	-0.12	0.17	-9999	-0.54	15	15
JUN	-0.055	0.16	-9999	-0.9	14	14
PPARGC1A	-0.22	0.37	-9999	-0.58	385	385
USF1	-0.09	0.19	-9999	-0.35	311	311
RAB5/GDP/GDI1	-0.085	0.12	-9999	-0.37	15	15
NOS2	-0.093	0.21	-9999	-0.77	17	17
DDIT3	-0.09	0.19	-9999	-0.35	311	311
RAB5A	0	0	-9999	-10000	0	0
HSPB1	-0.071	0.16	-9999	-0.42	37	37
p38alpha-beta/HBP1	-0.12	0.17	-9999	-0.35	311	311
CREB1	-0.094	0.2	-9999	-0.37	311	311
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.07	0.17	-9999	-0.48	14	14
RPS6KA4	-0.09	0.19	-9999	-0.35	311	311
PLA2G4A	-0.13	0.27	-9999	-0.73	108	108
GDI1	-0.09	0.19	-9999	-0.35	311	311
TP53	-0.12	0.24	-9999	-0.44	311	311
RPS6KA5	-0.094	0.2	-9999	-0.36	318	318
ESR1	-0.17	0.25	-9999	-0.42	421	421
HBP1	0	0	-9999	-10000	0	0
MEF2C	-0.091	0.19	-9999	-0.36	311	311
MEF2A	-0.09	0.19	-9999	-0.35	311	311
EIF4EBP1	-0.093	0.2	-9999	-0.37	311	311
KRT19	-0.1	0.21	-9999	-0.38	314	314
ELK4	-0.09	0.19	-9999	-0.35	311	311
ATF6	-0.09	0.19	-9999	-0.35	311	311
ATF1	-0.094	0.2	-9999	-0.37	311	311
p38alpha-beta/MAPKAPK2	-0.12	0.17	-9999	-0.53	16	16
p38alpha-beta/MAPKAPK3	-0.12	0.17	-9999	-0.35	311	311

×

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	0.46	-9999	-1	249	249
HDAC7	0	0	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.33	0.31	-9999	-0.78	199	199
SMAD4	0	0	-9999	-10000	0	0
ID2	-0.42	0.46	-9999	-0.99	251	251
AP1	-0.2	0.3	-9999	-0.65	284	284
ABCG2	-0.44	0.49	-9999	-1.1	259	259
HIF1A	-0.053	0.062	-9999	-10000	0	0
TFF3	-0.49	0.52	-9999	-1.1	325	325
GATA2	-0.015	0.13	-9999	-0.78	25	25
AKT1	-0.055	0.08	-9999	-10000	0	0
response to hypoxia	-0.077	0.086	-9999	-0.25	33	33
MCL1	-0.42	0.46	-9999	-0.99	251	251
NDRG1	-0.42	0.46	-9999	-1	247	247
SERPINE1	-0.42	0.46	-9999	-1	249	249
FECH	-0.42	0.46	-9999	-1	249	249
FURIN	-0.42	0.46	-9999	-0.99	250	250
NCOA2	-0.01	0.11	-9999	-0.82	17	17
EP300	-0.056	0.12	-9999	-0.36	50	50
HMOX1	-0.42	0.46	-9999	-1	249	249
BHLHE40	-0.42	0.46	-9999	-1	249	249
BHLHE41	-0.42	0.47	-9999	-1	250	250
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.05	0.052	-9999	-10000	0	0
ENG	-0.039	0.048	-9999	-10000	0	0
JUN	-0.008	0.082	-9999	-0.83	9	9
RORA	-0.42	0.46	-9999	-0.99	251	251
ABCB1	-0.34	0.55	-9999	-1.5	173	173
TFRC	-0.42	0.46	-9999	-1	249	249
CXCR4	-0.42	0.46	-9999	-1	250	250
TF	-0.67	0.58	-9999	-1.1	497	497
CITED2	-0.42	0.46	-9999	-1	249	249
HIF1A/ARNT	-0.5	0.51	-9999	-1.2	255	255
LDHA	-0.05	0.047	-9999	-10000	0	0
ETS1	-0.42	0.46	-9999	-1	250	250
PGK1	-0.42	0.46	-9999	-1	247	247
NOS2	-0.42	0.46	-9999	-1	251	251
ITGB2	-0.42	0.46	-9999	-1	249	249
ALDOA	-0.42	0.46	-9999	-1	247	247
Cbp/p300/CITED2	-0.43	0.44	-9999	-1	236	236
FOS	-0.26	0.38	-9999	-0.83	283	283
HK2	-0.42	0.46	-9999	-1	251	251
SP1	0.012	0.023	-9999	-10000	0	0
GCK	-0.15	0.39	-9999	-1.6	54	54
HK1	-0.42	0.46	-9999	-1	249	249
NPM1	-0.42	0.46	-9999	-1	249	249
EGLN1	-0.42	0.46	-9999	-1	249	249
CREB1	0.018	0	-9999	-10000	0	0
PGM1	-0.42	0.46	-9999	-1	249	249
SMAD3	0	0	-9999	-10000	0	0
EDN1	-0.2	0.41	-9999	-1.2	113	113
IGFBP1	-0.52	0.53	-9999	-1.1	329	329
VEGFA	-0.25	0.31	-9999	-0.75	109	109
HIF1A/JAB1	-0.029	0.026	-9999	-10000	0	0
CP	-0.53	0.55	-9999	-1.1	346	346
CXCL12	-0.44	0.5	-9999	-1.1	261	261
COPS5	0.002	0.011	-9999	-10000	0	0
SMAD3/SMAD4	0	0	-9999	-10000	0	0
BNIP3	-0.42	0.46	-9999	-1	249	249
EGLN3	-0.42	0.46	-9999	-1	255	255
CA9	-0.46	0.48	-9999	-1	264	264
TERT	-0.43	0.47	-9999	-1	252	252
ENO1	-0.42	0.46	-9999	-1	248	248
PFKL	-0.42	0.46	-9999	-1	244	244
NCOA1	-0.001	0.027	-9999	-0.82	1	1
ADM	-0.45	0.49	-9999	-1.1	271	271
ARNT	-0.058	0.053	-9999	-10000	0	0
HNF4A	-0.001	0.039	-9999	-0.37	1	1
ADFP	-0.42	0.46	-9999	-1	253	253
SLC2A1	-0.25	0.32	-9999	-0.76	111	111
LEP	-0.78	0.52	-9999	-1.1	589	589
HIF1A/ARNT/Cbp/p300	-0.35	0.32	-9999	-0.81	200	200
EPO	-0.23	0.25	-9999	-0.77	23	23
CREBBP	-0.056	0.12	-9999	-0.36	51	51
HIF1A/ARNT/Cbp/p300/HDAC7	-0.32	0.31	-9999	-0.79	184	184
PFKFB3	-0.42	0.46	-9999	-1	253	253
NT5E	-0.42	0.46	-9999	-1	249	249

×

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	0.021	-9999	-0.63	1	1
Necdin/E2F1	-0.078	0.15	-9999	-0.71	33	33
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.16	0.23	-9999	-0.48	305	305
NGF (dimer)/p75(NTR)/BEX1	-0.28	0.33	-9999	-0.65	374	374
NT-4/5 (dimer)/p75(NTR)	-0.42	0.43	-9999	-0.8	483	483
IKBKB	-0.001	0.013	-9999	-10000	0	0
AKT1	-0.16	0.23	-9999	-0.47	304	304
IKBKG	0	0	-9999	-10000	0	0
BDNF	-0.073	0.23	-9999	-0.82	74	74
MGDIs/NGR/p75(NTR)/LINGO1	-0.21	0.26	-9999	-0.58	296	296
FURIN	-0.001	0.013	-9999	-0.28	2	2
proBDNF (dimer)/p75(NTR)/Sortilin	-0.22	0.3	-9999	-0.6	337	337
LINGO1	-0.065	0.12	-9999	-10000	0	0
Sortilin/TRAF6/NRIF	-0.001	0.027	-9999	-0.82	1	1
proBDNF (dimer)	-0.073	0.23	-9999	-0.82	74	74
NTRK1	-0.01	0.065	-9999	-0.82	3	3
RTN4R	-0.009	0.048	-9999	-0.28	28	28
neuron apoptosis	-0.16	0.28	-9999	-0.51	296	296
IRAK1	-0.001	0.016	-9999	-0.28	3	3
SHC1	-0.17	0.28	-9999	-0.56	303	303
ARHGDIA	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	-0.001	0.016	-9999	-0.47	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.17	0.25	-9999	-0.51	303	303
MAGEH1	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.19	0.27	-9999	-0.55	314	314
Mammalian IAPs/DIABLO	-0.006	0.048	-9999	-0.5	8	8
proNGF (dimer)	-0.016	0.11	-9999	-0.65	22	22
MAGED1	-0.001	0.013	-9999	-0.28	2	2
APP	0	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.3	0.4	-9999	-0.82	338	338
ZNF274	0	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.16	0.23	-9999	-0.48	303	303
NGF	-0.016	0.11	-9999	-0.65	22	22
cell cycle arrest	-0.13	0.25	-9999	-0.46	303	303
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.11	0.16	-9999	-0.34	303	303
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.37	0.39	-9999	-0.7	483	483
NCSTN	0	0	-9999	-10000	0	0
mol:GTP	-0.19	0.27	-9999	-0.57	303	303
PSENEN	0	0.009	-9999	-0.28	1	1
mol:ceramide	-0.17	0.24	-9999	-0.51	303	303
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.09	0.13	-9999	-0.48	14	14
p75(NTR)/beta APP	-0.2	0.3	-9999	-0.63	296	296
BEX1	-0.16	0.29	-9999	-0.82	127	127
mol:GDP	-0.18	0.28	-9999	-0.57	303	303
NGF (dimer)	-0.085	0.19	-9999	-0.52	142	142
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.19	0.24	-9999	-0.53	296	296
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
RAC1/GTP	-0.16	0.24	-9999	-0.49	303	303
MYD88	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.2	0.28	-9999	-0.58	303	303
RHOB	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.056	0.082	-9999	-10000	0	0
NT3 (dimer)	-0.14	0.3	-9999	-0.82	149	149
TP53	-0.18	0.25	-9999	-0.48	337	337
PRDM4	-0.17	0.24	-9999	-0.51	303	303
BDNF (dimer)	-0.17	0.24	-9999	-0.6	192	192
PIK3CA	0	0.009	-9999	-10000	0	0
SORT1	-0.001	0.027	-9999	-0.82	1	1
activation of caspase activity	-0.16	0.23	-9999	-0.47	305	305
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.17	0.25	-9999	-0.51	303	303
RHOC	0	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
MAPK10	-0.17	0.28	-9999	-0.51	308	308
DIABLO	0	0	-9999	-10000	0	0
SMPD2	-0.17	0.24	-9999	-0.51	303	303
APH1B	-0.001	0.027	-9999	-0.82	1	1
APH1A	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.19	0.27	-9999	-0.56	303	303
PSEN1	0	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.3	0.38	-9999	-0.72	383	383
MAPK8	-0.12	0.25	-9999	-0.45	296	296
MAPK9	-0.12	0.25	-9999	-0.45	296	296
APAF1	0	0	-9999	-10000	0	0
NTF3	-0.14	0.3	-9999	-0.82	149	149
NTF4	-0.3	0.4	-9999	-0.82	338	338
NDN	-0.03	0.15	-9999	-0.82	33	33
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.15	0.22	-9999	-0.45	303	303
p75 CTF/Sortilin/TRAF6/NRIF	-0.001	0.016	-9999	-0.5	1	1
RhoA-B-C/GTP	-0.19	0.27	-9999	-0.57	303	303
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.19	0.26	-9999	-0.52	337	337
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.2	0.28	-9999	-0.55	337	337
PRKACB	-0.017	0.077	-9999	-0.82	3	3
proBDNF (dimer)/p75 ECD	-0.055	0.17	-9999	-0.63	74	74
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.01	0.082	-9999	-0.82	8	8
BIRC2	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.14	0.27	-9999	-0.49	303	303
BAD	-0.13	0.25	-9999	-0.46	298	298
RIPK2	-0.002	0.021	-9999	-0.28	5	5
NGFR	-0.27	0.39	-9999	-0.82	296	296
CYCS	-0.16	0.23	-9999	-0.48	303	303
ADAM17	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.17	0.24	-9999	-0.51	303	303
BCL2L11	-0.13	0.25	-9999	-0.46	298	298
BDNF (dimer)/p75(NTR)	-0.26	0.34	-9999	-0.69	337	337
PI3K	-0.17	0.24	-9999	-0.51	304	304
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.17	0.25	-9999	-0.51	303	303
NDNL2	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
PRKCI	0	0.009	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.22	0.31	-9999	-0.65	303	303
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.17	0.25	-9999	-0.51	303	303
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
PRKCZ	-0.001	0.027	-9999	-0.82	1	1
PLG	-0.001	0.018	-9999	-0.28	4	4
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.21	0.28	-9999	-0.55	344	344
SQSTM1	-0.001	0.013	-9999	-10000	0	0
NGFRAP1	-0.002	0.039	-9999	-0.82	2	2
CASP3	-0.12	0.23	-9999	-0.43	298	298
E2F1	-0.089	0.13	-9999	-0.28	292	292
CASP9	0	0	-9999	-10000	0	0
IKK complex	-0.071	0.12	-9999	-0.59	19	19
NGF (dimer)/TRKA	-0.018	0.093	-9999	-0.63	18	18
MMP7	-0.12	0.29	-9999	-0.73	155	155
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.16	0.23	-9999	-0.48	303	303
MMP3	-0.12	0.16	-9999	-0.3	359	359
APAF-1/Caspase 9	-0.12	0.17	-9999	-0.68	14	14

×

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	0.024	0.078	0.36	2	-10000	0	2
SMARCC2	0.011	0.009	-10000	0	-10000	0	0
SMARCC1	0.011	0.009	-10000	0	-10000	0	0
TBX21	-0.14	0.26	-10000	0	-0.69	103	103
SUMO2	0	0.01	-10000	0	-10000	0	0
STAT1 (dimer)	0.012	0.042	-10000	0	-0.34	1	1
FKBP4	-0.002	0.024	-10000	0	-0.28	7	7
FKBP5	-0.013	0.099	-10000	0	-0.82	13	13
GR alpha/HSP90/FKBP51/HSP90	0.12	0.14	0.33	72	-0.44	15	87
PRL	-0.091	0.12	-10000	0	-0.57	1	1
cortisol/GR alpha (dimer)/TIF2	0.29	0.28	0.52	448	-0.61	12	460
RELA	-0.041	0.083	-10000	0	-10000	0	0
FGG	0.24	0.22	0.46	359	-0.55	2	361
GR beta/TIF2	0.12	0.16	0.32	163	-0.61	19	182
IFNG	-0.44	0.35	-10000	0	-0.76	432	432
apoptosis	-0.28	0.3	0.59	3	-0.66	249	252
CREB1	-0.008	0.028	-10000	0	-10000	0	0
histone acetylation	0.022	0.14	0.4	30	-0.4	24	54
BGLAP	-0.1	0.15	-10000	0	-0.49	26	26
GR/PKAc	0.12	0.12	0.32	59	-0.52	3	62
NF kappa B1 p50/RelA	-0.07	0.15	-10000	0	-0.42	29	29
SMARCD1	0.011	0.009	-10000	0	-10000	0	0
MDM2	0.12	0.1	0.24	290	-10000	0	290
GATA3	-0.028	0.16	-10000	0	-0.58	60	60
AKT1	0	0.004	-10000	0	-10000	0	0
CSF2	-0.041	0.11	-10000	0	-0.58	6	6
GSK3B	0	0.004	-10000	0	-10000	0	0
NR1I3	-0.21	0.27	0.56	3	-0.62	150	153
CSN2	0.2	0.18	0.41	220	-0.56	1	221
BRG1/BAF155/BAF170/BAF60A	-0.002	0.03	-10000	0	-0.46	4	4
NFATC1	0.002	0.028	-10000	0	-0.82	1	1
POU2F1	0.007	0.013	-10000	0	-0.28	1	1
CDKN1A	0.046	0.059	-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	0.1	-10000	0	-0.54	27	27
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.1	0.14	0.32	61	-0.4	25	86
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.38	0.44	0.54	3	-0.91	327	330
JUN	-0.32	0.29	-10000	0	-0.57	439	439
IL4	-0.13	0.15	-10000	0	-0.5	34	34
CDK5R1	-0.009	0.049	-10000	0	-0.28	28	28
PRKACA	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.44	0.42	-10000	0	-0.75	516	516
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.11	0.13	0.34	48	-0.43	9	57
cortisol/GR alpha (monomer)	0.36	0.32	0.62	472	-0.57	2	474
NCOA2	-0.015	0.11	-10000	0	-0.82	17	17
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.3	0.4	-10000	0	-0.89	283	283
AP-1/NFAT1-c-4	-0.68	0.53	-10000	0	-1	596	596
AFP	-0.62	0.71	-10000	0	-1.5	335	335
SUV420H1	0	0	-10000	0	-10000	0	0
IRF1	0.2	0.16	0.41	199	-10000	0	199
TP53	0.031	0.018	-10000	0	-0.5	1	1
PPP5C	0	0	-10000	0	-10000	0	0
KRT17	-0.87	0.82	-10000	0	-1.6	462	462
KRT14	-0.87	0.78	-10000	0	-1.6	498	498
TBP	0.019	0.003	-10000	0	-10000	0	0
CREBBP	0.15	0.14	0.3	184	-10000	0	184
HDAC1	0	0.003	-10000	0	-10000	0	0
HDAC2	0.001	0.004	-10000	0	-10000	0	0
AP-1	-0.69	0.54	-10000	0	-1	596	596
MAPK14	0	0.003	-10000	0	-10000	0	0
MAPK10	-0.13	0.3	-10000	0	-0.83	144	144
MAPK11	-0.001	0.04	-10000	0	-0.84	2	2
KRT5	-0.96	0.82	-10000	0	-1.7	504	504
interleukin-1 receptor activity	-0.001	0.003	-10000	0	-10000	0	0
NCOA1	0.007	0.028	-10000	0	-0.82	1	1
STAT1	0.012	0.042	-10000	0	-0.34	1	1
CGA	-0.16	0.18	-10000	0	-0.47	126	126
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.21	0.18	0.37	455	-10000	0	455
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	-0.58	178	178
NFKB1	-0.041	0.083	-10000	0	-0.26	3	3
MAPK8	-0.24	0.22	-10000	0	-0.43	406	406
MAPK9	0	0.003	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.3	0.32	0.59	3	-0.7	251	254
BAX	0.048	0.03	-10000	0	-10000	0	0
POMC	-0.2	0.31	-10000	0	-0.95	77	77
EP300	0.15	0.14	0.31	131	-10000	0	131
cortisol/GR alpha (dimer)/p53	0.32	0.26	0.54	448	-0.59	1	449
proteasomal ubiquitin-dependent protein catabolic process	0.089	0.079	0.22	90	-10000	0	90
SGK1	0.23	0.2	-10000	0	-1.2	4	4
IL13	-0.32	0.28	-10000	0	-0.67	230	230
IL6	-0.51	0.64	-10000	0	-1.3	343	343
PRKACG	0	0	-10000	0	-10000	0	0
IL5	-0.28	0.22	-10000	0	-0.5	377	377
IL2	-0.43	0.35	-10000	0	-0.72	477	477
CDK5	-0.001	0.021	-10000	0	-0.29	3	3
PRKACB	-0.017	0.077	-10000	0	-0.82	3	3
HSP90AA1	0	0.009	-10000	0	-10000	0	0
IL8	-0.21	0.31	-10000	0	-0.61	245	245
CDK5R1/CDK5	-0.006	0.035	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.06	0.098	-10000	0	-0.6	4	4
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.29	0.24	0.5	448	-0.55	1	449
SMARCA4	0.011	0.013	-10000	0	-0.28	1	1
chromatin remodeling	0.2	0.16	0.37	307	-10000	0	307
NF kappa B1 p50/RelA/Cbp	0.057	0.17	0.35	39	-10000	0	39
JUN (dimer)	-0.32	0.29	-10000	0	-0.57	440	440
YWHAH	0	0	-10000	0	-10000	0	0
VIPR1	-0.14	0.25	-10000	0	-0.79	76	76
NR3C1	0.2	0.2	0.41	351	-0.55	5	356
NR4A1	-0.065	0.24	-10000	0	-0.76	96	96
TIF2/SUV420H1	-0.012	0.086	-10000	0	-0.63	17	17
MAPKKK cascade	-0.28	0.3	0.59	3	-0.66	249	252
cortisol/GR alpha (dimer)/Src-1	0.31	0.26	0.53	454	-0.6	1	455
PBX1	0.005	0.042	-10000	0	-0.82	2	2
POU1F1	0.003	0.012	-10000	0	-0.28	1	1
SELE	-0.23	0.36	-10000	0	-0.71	238	238
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.2	0.16	0.38	303	-10000	0	303
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.29	0.24	0.5	448	-0.55	1	449
mol:cortisol	0.2	0.2	0.36	481	-10000	0	481
MMP1	-0.21	0.1	-10000	0	-10000	0	0

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.46	0.45	-10000	0	-1	264	264
STAT6 (cleaved dimer)	-0.5	0.44	-10000	0	-0.92	394	394
IGHG1	-0.16	0.16	-10000	0	-0.34	186	186
IGHG3	-0.45	0.44	-10000	0	-0.89	372	372
AKT1	-0.21	0.24	-10000	0	-0.59	105	105
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.15	0.19	-10000	0	-0.56	53	53
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.22	0.24	-10000	0	-0.57	148	148
THY1	-0.46	0.45	-10000	0	-1	266	266
MYB	-0.014	0.11	-10000	0	-0.82	15	15
HMGA1	-0.011	0.055	-10000	0	-0.28	37	37
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.28	0.29	-10000	0	-0.62	246	246
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.21	0.23	-10000	0	-0.54	128	128
SP1	0.017	0.005	-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	-0.92	369	369
SOCS1	-0.3	0.3	-10000	0	-0.72	191	191
SOCS3	-0.23	0.26	-10000	0	-0.81	57	57
FCER2	-0.61	0.65	-10000	0	-1.4	331	331
PARP14	0	0.018	-10000	0	-0.29	3	3
CCL17	-0.47	0.45	-10000	0	-1	264	264
GRB2	0	0.009	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.17	0.19	-10000	0	-0.51	38	38
T cell proliferation	-0.46	0.47	-10000	0	-1	279	279
IL4R/JAK1	-0.46	0.45	-10000	0	-1	270	270
EGR2	-0.61	0.63	-10000	0	-1.3	347	347
JAK2	-0.008	0.038	-10000	0	-0.85	1	1
JAK3	0.008	0.038	-10000	0	-0.28	6	6
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
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	256	256
IL4R	-0.49	0.48	-10000	0	-1.1	272	272
PTPN6	0.022	0.018	-10000	0	-0.26	2	2
IL13RA2	-0.46	0.46	-10000	0	-1	249	249
IL13RA1	-0.007	0.025	-10000	0	-10000	0	0
IRF4	-0.22	0.47	-10000	0	-1.6	92	92
ARG1	-0.11	0.12	-10000	0	-10000	0	0
CBL	-0.26	0.27	-10000	0	-0.62	201	201
GTF3A	0.013	0.016	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.014	0.042	-10000	0	-0.65	1	1
IRF4/BCL6	-0.2	0.42	-10000	0	-1.4	95	95
CD40LG	-0.033	0.19	-10000	0	-0.79	49	49
MAPK14	-0.26	0.27	-10000	0	-0.62	198	198
mitosis	-0.2	0.23	-10000	0	-0.56	105	105
STAT6	-0.52	0.52	-10000	0	-1.1	360	360
SPI1	0.006	0.026	-10000	0	-0.27	7	7
RPS6KB1	-0.19	0.22	-10000	0	-0.57	78	78
STAT6 (dimer)	-0.52	0.52	-10000	0	-1.1	360	360
STAT6 (dimer)/PARP14	-0.51	0.5	-10000	0	-1	376	376
mast cell activation	0.012	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.2	0.23	-10000	0	-0.55	116	116
FRAP1	-0.21	0.24	-10000	0	-0.59	105	105
LTA	-0.47	0.45	-10000	0	-1.1	244	244
FES	-0.003	0.047	-10000	0	-0.82	3	3
T-helper 1 cell differentiation	0.51	0.51	1	360	-10000	0	360
CCL11	-0.48	0.44	-10000	0	-1	283	283
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.2	0.23	-10000	0	-0.55	118	118
IL2RG	-0.004	0.084	-10000	0	-0.82	5	5
IL10	-0.46	0.46	-10000	0	-1	257	257
IRS1	-0.033	0.16	-10000	0	-0.82	36	36
IRS2	-0.034	0.16	-10000	0	-0.82	38	38
IL4	-0.11	0.11	-10000	0	-10000	0	0
IL5	-0.47	0.45	-10000	0	-0.95	336	336
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.38	0.36	-10000	0	-0.76	332	332
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	-1.1	215	215
IL2R gamma/JAK3	-0.014	0.069	-10000	0	-0.43	19	19
TFF3	-0.56	0.58	-10000	0	-1.2	360	360
ALOX15	-0.55	0.57	-10000	0	-1.2	304	304
MYBL1	-0.044	0.1	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.4	0.37	-10000	0	-0.78	353	353
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	-0.21	0.23	-10000	0	-0.55	132	132
mol:PI-3-4-5-P3	-0.21	0.24	-10000	0	-0.59	105	105
PI3K	-0.22	0.25	-10000	0	-0.63	104	104
DOK2	-0.003	0.043	-10000	0	-0.82	2	2
ETS1	0.02	0.04	-10000	0	-0.79	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.15	0.18	-10000	0	-0.53	25	25
ITGB3	-0.47	0.48	-10000	0	-1.1	252	252
PIGR	-1	0.75	-10000	0	-1.5	598	598
IGHE	0.046	0.039	-10000	0	-10000	0	0
MAPKKK cascade	-0.15	0.17	-10000	0	-0.52	25	25
BCL6	0.002	0.048	-10000	0	-0.82	3	3
OPRM1	-0.47	0.45	-10000	0	-1	276	276
RETNLB	-0.47	0.45	-10000	0	-1	272	272
SELP	-0.64	0.68	-10000	0	-1.5	315	315
AICDA	-0.45	0.44	-10000	0	-0.98	275	275

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.24	0.28	-9999	-0.8	93	93
PCK1	-1	0.72	-9999	-1.6	562	562
HNF4A	-0.25	0.28	-9999	-0.87	65	65
KCNJ11	-0.27	0.31	-9999	-0.84	129	129
AKT1	-0.15	0.14	-9999	-0.39	38	38
response to starvation	-0.001	0.006	-9999	-10000	0	0
DLK1	-0.5	0.57	-9999	-1.2	307	307
NKX2-1	-0.058	0.15	-9999	-10000	0	0
ACADM	-0.25	0.28	-9999	-0.78	114	114
TAT	-1.2	0.68	-9999	-1.6	670	670
CEBPB	0.003	0.005	-9999	-10000	0	0
CEBPA	-0.003	0.078	-9999	-0.82	8	8
TTR	-0.45	0.28	-9999	-0.8	242	242
PKLR	-0.25	0.28	-9999	-0.78	108	108
APOA1	-0.3	0.3	-9999	-0.86	109	109
CPT1C	-0.24	0.28	-9999	-0.79	103	103
ALAS1	-0.14	0.15	-9999	-10000	0	0
TFRC	-0.45	0.26	-9999	-0.74	281	281
FOXF1	-0.003	0.053	-9999	-0.46	9	9
NF1	0.016	0.028	-9999	-0.82	1	1
HNF1A (dimer)	0.003	0.024	-9999	-10000	0	0
CPT1A	-0.24	0.28	-9999	-0.81	90	90
HMGCS1	-0.24	0.28	-9999	-0.77	113	113
NR3C1	-0.11	0.12	-9999	-0.38	69	69
CPT1B	-0.25	0.28	-9999	-0.81	94	94
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.002	0.006	-9999	-10000	0	0
GCK	-0.29	0.36	-9999	-0.97	138	138
CREB1	-0.057	0.066	-9999	-10000	0	0
IGFBP1	-0.47	0.61	-9999	-1.5	217	217
PDX1	-0.13	0.14	-9999	-10000	0	0
UCP2	-0.24	0.28	-9999	-0.82	85	85
ALDOB	-0.27	0.3	-9999	-0.9	83	83
AFP	-0.69	0.62	-9999	-0.98	616	616
BDH1	-0.24	0.28	-9999	-0.77	114	114
HADH	-0.27	0.3	-9999	-0.86	91	91
F2	-0.3	0.3	-9999	-0.92	73	73
HNF1A	0.003	0.024	-9999	-10000	0	0
G6PC	-0.2	0.12	-9999	-0.68	6	6
SLC2A2	-0.16	0.17	-9999	-0.54	4	4
INS	0.025	0.068	-9999	-10000	0	0
FOXA1	-0.24	0.28	-9999	-0.61	230	230
FOXA3	-0.43	0.23	-9999	-0.54	635	635
FOXA2	-0.32	0.34	-9999	-0.86	167	167
ABCC8	-0.35	0.44	-9999	-1.1	164	164
ALB	-0.95	0.65	-9999	-1.4	594	594

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.074	0.15	-10000	0	-0.32	241	241
NFATC2	-0.041	0.25	-10000	0	-0.78	80	80
NFATC3	-0.062	0.12	-10000	0	-10000	0	0
CD40LG	-0.38	0.58	-10000	0	-1.1	289	289
ITCH	0.012	0.1	-10000	0	-10000	0	0
CBLB	0.012	0.1	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.24	0.34	-10000	0	-1.1	83	83
JUNB	0	0.009	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.037	0.11	-10000	0	-10000	0	0
T cell anergy	-0.026	0.17	-10000	0	-0.48	97	97
TLE4	-0.018	0.24	-10000	0	-0.8	59	59
Jun/NFAT1-c-4/p21SNFT	-0.3	0.44	-10000	0	-0.93	257	257
AP-1/NFAT1-c-4	-0.53	0.66	-10000	0	-1.3	319	319
IKZF1	-0.007	0.19	-10000	0	-0.62	62	62
T-helper 2 cell differentiation	-0.1	0.29	-10000	0	-0.81	90	90
AP-1/NFAT1	-0.23	0.33	-10000	0	-0.66	313	313
CALM1	-0.019	0.055	-10000	0	-10000	0	0
EGR2	-0.3	0.66	-10000	0	-1.5	167	167
EGR3	-0.39	0.74	-10000	0	-1.5	253	253
NFAT1/FOXP3	-0.099	0.2	-10000	0	-0.6	81	81
EGR1	-0.27	0.38	-10000	0	-0.82	295	295
JUN	-0.012	0.083	-10000	0	-0.83	9	9
EGR4	-0.019	0.069	-10000	0	-0.28	61	61
mol:Ca2+	-0.022	0.064	-10000	0	-10000	0	0
GBP3	-0.013	0.21	-10000	0	-0.71	60	60
FOSL1	-0.008	0.056	-10000	0	-0.82	2	2
NFAT1-c-4/MAF/IRF4	-0.32	0.47	-10000	0	-0.95	273	273
DGKA	-0.006	0.19	-10000	0	-0.65	51	51
CREM	0	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.4	0.53	-10000	0	-1.1	299	299
CTLA4	-0.075	0.22	-10000	0	-0.66	58	58
NFAT1-c-4 (dimer)/EGR1	-0.44	0.58	-10000	0	-1.2	301	301
NFAT1-c-4 (dimer)/EGR4	-0.29	0.46	-10000	0	-0.91	295	295
FOS	-0.26	0.38	-10000	0	-0.84	283	283
IFNG	-0.14	0.26	-10000	0	-0.85	79	79
T cell activation	-0.17	0.35	-10000	0	-0.76	192	192
MAF	-0.001	0.027	-10000	0	-0.82	1	1
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.17	0.36	0.68	252	-10000	0	252
TNF	-0.33	0.53	-10000	0	-1.1	273	273
FASLG	-0.36	0.68	-10000	0	-1.3	294	294
TBX21	-0.025	0.17	-10000	0	-0.7	47	47
BATF3	-0.002	0.033	-10000	0	-0.39	5	5
PRKCQ	-0.023	0.16	-10000	0	-0.68	47	47
PTPN1	-0.007	0.19	-10000	0	-0.64	58	58
NFAT1-c-4/ICER1	-0.3	0.44	-10000	0	-0.9	294	294
GATA3	-0.036	0.16	-10000	0	-0.58	60	60
T-helper 1 cell differentiation	-0.14	0.25	-10000	0	-0.83	79	79
IL2RA	-0.23	0.33	-10000	0	-0.92	98	98
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.006	0.19	-10000	0	-0.63	58	58
E2F1	-0.075	0.13	-10000	0	-10000	0	0
PPARG	-0.19	0.35	-10000	0	-0.82	209	209
SLC3A2	-0.006	0.19	-10000	0	-0.63	59	59
IRF4	-0.072	0.23	-10000	0	-0.76	87	87
PTGS2	-0.49	0.66	-10000	0	-1.2	386	386
CSF2	-0.37	0.56	-10000	0	-1.1	288	288
JunB/Fra1/NFAT1-c-4	-0.28	0.43	-10000	0	-0.89	261	261
IL4	-0.11	0.3	-10000	0	-0.86	89	89
IL5	-0.37	0.56	-10000	0	-1.1	314	314
IL2	-0.18	0.36	-10000	0	-0.78	189	189
IL3	-0.064	0.066	-10000	0	-10000	0	0
RNF128	-0.058	0.29	-10000	0	-0.88	98	98
NFATC1	-0.17	0.36	-10000	0	-0.69	242	242
CDK4	0.086	0.23	0.6	30	-10000	0	30
PTPRK	-0.009	0.2	-10000	0	-0.64	70	70
IL8	-0.38	0.57	-10000	0	-1.1	301	301
POU2F1	0.001	0.01	-10000	0	-0.28	1	1

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0	0	-9999	-10000	0	0
VLDLR	-0.023	0.14	-9999	-0.82	25	25
LRPAP1	0	0	-9999	-10000	0	0
NUDC	0	0	-9999	-10000	0	0
RELN/LRP8	-0.35	0.27	-9999	-0.57	564	564
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0	0.009	-9999	-0.28	1	1
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.32	0.25	-9999	-0.51	564	564
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.017	0.067	-9999	-0.28	56	56
IQGAP1	0	0	-9999	-10000	0	0
PLA2G7	-0.015	0.09	-9999	-0.82	8	8
CALM1	0	0	-9999	-10000	0	0
DYNLT1	0	0.009	-9999	-0.28	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.02	0.056	-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	-0.28	28	28
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.041	0.098	-9999	-0.28	133	133
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.36	0.29	-9999	-0.57	570	570
YWHAE	0	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.25	0.2	-9999	-0.46	161	161
MAP1B	-0.007	0.05	-9999	-0.38	16	16
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.28	0.22	-9999	-0.45	564	564
RELN	-0.51	0.4	-9999	-0.82	564	564
PAFAH/LIS1	-0.009	0.056	-9999	-0.55	8	8
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.19	0.15	-9999	-0.41	23	23
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.21	0.17	-9999	-0.37	208	208
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.27	0.21	-9999	-0.43	564	564
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.022	0	-9999	-10000	0	0
PAFAH1B3	-0.027	0.083	-9999	-10000	0	0
PAFAH1B2	-0.002	0.039	-9999	-0.82	2	2
MAP1B/LIS1/Dynein heavy chain	-0.004	0.032	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.24	0.19	-9999	-0.47	88	88
LRP8	-0.032	0.089	-9999	-0.28	105	105
NDEL1/Katanin 60	-0.25	0.2	-9999	-0.46	162	162
P39/CDK5	-0.29	0.23	-9999	-0.47	564	564
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.28	0.25	-9999	-0.48	564	564
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	-0.31	0.25	-9999	-0.49	570	570
RELN/VLDLR	-0.34	0.26	-9999	-0.53	570	570
CDC42	0	0	-9999	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.004	0.048	-9999	-0.68	4	4
ARNO/beta Arrestin1-2	-0.14	0.2	-9999	-0.45	223	223
EGFR	-0.3	0.4	-9999	-0.82	331	331
EPHA2	-0.005	0.067	-9999	-0.82	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	-0.7	453	453
ARRB2	-0.063	0.16	-9999	-0.45	128	128
mol:GTP	0.017	0.019	-9999	-0.16	5	5
ARRB1	-0.002	0.04	-9999	-0.64	3	3
FBXO8	0	0	-9999	-10000	0	0
TSHR	-0.038	0.17	-9999	-0.78	45	45
EGF	-0.16	0.33	-9999	-0.82	183	183
somatostatin receptor activity	0	0	-9999	-0.001	309	309
ARAP2	-0.005	0.067	-9999	-0.82	6	6
mol:GDP	-0.14	0.18	-9999	-0.36	275	275
mol:PI-3-4-5-P3	0	0	-9999	-0.001	221	221
ITGA2B	-0.016	0.076	-9999	-0.31	47	47
ARF6	0	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.004	0.041	-9999	-0.5	6	6
ADAP1	-0.004	0.051	-9999	-0.82	3	3
KIF13B	-0.002	0.039	-9999	-0.82	2	2
HGF/MET	-0.14	0.29	-9999	-0.68	193	193
PXN	0	0	-9999	-10000	0	0
ARF6/GTP	-0.13	0.16	-9999	-0.32	298	298
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.3	0.32	-9999	-0.61	453	453
ADRB2	-0.2	0.36	-9999	-0.83	223	223
receptor agonist activity	0	0	-9999	0	306	306
actin filament binding	0	0	-9999	-0.001	299	299
SRC	0	0.009	-9999	-10000	0	0
ITGB3	-0.018	0.12	-9999	-0.82	19	19
GNAQ	-0.002	0.039	-9999	-0.83	2	2
EFA6/PI-4-5-P2	0	0.001	-9999	-0.001	279	279
ARF6/GDP	-0.016	0.086	-9999	-0.42	17	17
ARF6/GDP/GULP/ACAP1	-0.15	0.2	-9999	-0.54	149	149
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.018	0.081	-9999	-0.5	22	22
ACAP1	-0.017	0.095	-9999	-0.4	39	39
ACAP2	0	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.095	0.24	-9999	-0.68	128	128
EFNA1	0	0.009	-9999	-10000	0	0
HGF	-0.051	0.2	-9999	-0.83	57	57
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	265	265
endosomal lumen acidification	0	0	-9999	-0.001	240	240
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.052	0.2	-9999	-0.82	58	58
GNAQ/ARNO	0.003	0.024	-9999	-0.48	2	2
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	303	303
MET	-0.14	0.31	-9999	-0.82	155	155
GNA14	-0.014	0.087	-9999	-0.42	30	30
GNA15	-0.003	0.035	-9999	-0.36	7	7
GIT1	-0.001	0.018	-9999	-0.28	4	4
mol:PI-4-5-P2	0	0	-9999	-0.001	298	298
GNA11	-0.002	0.039	-9999	-0.83	2	2
LHCGR	-0.12	0.29	-9999	-0.83	128	128
AGTR1	-0.21	0.34	-9999	-0.71	266	266
desensitization of G-protein coupled receptor protein signaling pathway	-0.095	0.24	-9999	-0.68	128	128
IPCEF1/ARNO	-0.24	0.26	-9999	-0.49	453	453
alphaIIb/beta3 Integrin	-0.024	0.1	-9999	-0.64	22	22

×

ErbB2/ErbB3 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	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	-0.39	19	19
NFATC4	-0.091	0.16	-9999	-0.31	153	153
ERBB2IP	0.007	0.008	-9999	-10000	0	0
HSP90 (dimer)	0	0.009	-9999	-10000	0	0
mammary gland morphogenesis	-0.15	0.19	-9999	-0.41	333	333
JUN	-0.019	0.079	-9999	-0.37	4	4
HRAS	-0.001	0.013	-9999	-0.28	2	2
DOCK7	-0.13	0.2	-9999	-0.38	333	333
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.18	0.23	-9999	-0.49	333	333
AKT1	0.007	0.006	-9999	-10000	0	0
BAD	0.018	0.004	-9999	-10000	0	0
MAPK10	-0.11	0.14	-9999	-0.37	145	145
mol:GTP	-0.001	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.16	0.21	-9999	-0.44	333	333
RAF1	-0.083	0.16	-9999	-0.4	14	14
ErbB2/ErbB3/neuregulin 2	-0.27	0.26	-9999	-0.53	463	463
STAT3	0	0.004	-9999	-10000	0	0
cell migration	-0.064	0.13	-9999	-0.32	74	74
mol:PI-3-4-5-P3	-0.002	0.003	-9999	-10000	0	0
cell proliferation	-0.14	0.23	-9999	-0.52	146	146
FOS	-0.17	0.26	-9999	-0.54	285	285
NRAS	-0.001	0.013	-9999	-0.28	2	2
mol:Ca2+	-0.15	0.19	-9999	-0.41	333	333
MAPK3	-0.11	0.19	-9999	-0.48	59	59
MAPK1	-0.11	0.19	-9999	-0.43	146	146
JAK2	-0.13	0.2	-9999	-0.38	334	334
NF2	-0.007	0.01	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.14	0.18	-9999	-0.37	333	333
NRG1	-0.3	0.4	-9999	-0.82	336	336
GRB2/SOS1	0	0.006	-9999	-10000	0	0
MAPK8	-0.11	0.17	-9999	-0.34	334	334
MAPK9	-0.071	0.091	-9999	-0.29	1	1
ERBB2	-0.017	0.054	-9999	-10000	0	0
ERBB3	-0.002	0.039	-9999	-0.83	2	2
SHC1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
apoptosis	0.016	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	21	21
ErbB2/ErbB2/HSP90 (dimer)	-0.013	0.042	-9999	-10000	0	0
CHRNA1	-0.094	0.16	-9999	-0.41	55	55
myelination	-0.085	0.16	-9999	-0.31	153	153
PPP3CB	-0.13	0.17	-9999	-0.36	333	333
KRAS	0	0.009	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.11	0.15	-9999	-0.31	333	333
NRG2	-0.42	0.41	-9999	-0.82	461	461
mol:GDP	-0.13	0.18	-9999	-0.36	333	333
SOS1	0	0	-9999	-10000	0	0
MAP2K2	-0.075	0.15	-9999	-0.4	14	14
SRC	0	0.009	-9999	-10000	0	0
mol:cAMP	-0.002	0.002	-9999	-10000	0	0
PTPN11	-0.14	0.18	-9999	-0.38	333	333
MAP2K1	-0.14	0.21	-9999	-0.49	145	145
heart morphogenesis	-0.15	0.19	-9999	-0.41	333	333
RAS family/GDP	-0.11	0.14	-9999	-0.39	14	14
GRB2	0	0.009	-9999	-10000	0	0
PRKACA	-0.011	0.014	-9999	-10000	0	0
CHRNE	0.007	0.021	-9999	-0.18	4	4
HSP90AA1	0	0.009	-9999	-10000	0	0
activation of caspase activity	-0.007	0.006	-9999	-10000	0	0
nervous system development	-0.15	0.19	-9999	-0.41	333	333
CDC42	0	0	-9999	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.11	0.4	-10000	0	-0.9	181	181
NCK1/PAK1/Dok-R	-0.084	0.17	-10000	0	-0.42	181	181
NCK1/Dok-R	-0.23	0.46	-10000	0	-1.1	181	181
PIK3CA	0.002	0.011	-10000	0	-10000	0	0
mol:beta2-estradiol	0.034	0.097	0.24	154	-10000	0	154
RELA	0	0	-10000	0	-10000	0	0
SHC1	0	0.001	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.036	0.1	0.29	8	-0.3	5	13
TNIP2	0	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.21	0.42	-10000	0	-1.1	181	181
FN1	-0.12	0.14	-10000	0	-10000	0	0
PLD2	-0.18	0.51	-10000	0	-1.2	181	181
PTPN11	0	0	-10000	0	-10000	0	0
GRB14	-0.1	0.23	-10000	0	-0.47	194	194
ELK1	-0.14	0.45	-10000	0	-1	181	181
GRB7	-0.021	0.076	-10000	0	-0.82	1	1
PAK1	-0.006	0.041	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.18	0.48	-10000	0	-1.1	181	181
CDKN1A	-0.054	0.27	-10000	0	-0.63	104	104
ITGA5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.23	0.46	-10000	0	-1.1	181	181
CRK	0	0	-10000	0	-10000	0	0
mol:NO	-0.057	0.3	-10000	0	-0.66	181	181
PLG	-0.18	0.51	-10000	0	-1.2	181	181
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.17	0.36	-10000	0	-0.88	181	181
GRB2	0	0.009	-10000	0	-10000	0	0
PIK3R1	0	0.028	-10000	0	-0.82	1	1
ANGPT2	-0.1	0.27	-10000	0	-0.76	89	89
BMX	-0.36	0.58	-10000	0	-1.4	181	181
ANGPT1	-0.22	0.56	-10000	0	-1.4	162	162
tube development	-0.07	0.3	-10000	0	-0.67	148	148
ANGPT4	-0.27	0.39	-10000	0	-0.83	296	296
response to hypoxia	-0.009	0.029	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.26	0.53	-10000	0	-1.3	181	181
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	-0.33	0.41	-10000	0	-0.82	370	370
STAT5A (dimer)	-0.085	0.34	-10000	0	-0.78	143	143
mol:L-citrulline	-0.057	0.3	-10000	0	-0.66	181	181
AGTR1	-0.2	0.34	-10000	0	-0.7	266	266
MAPK14	-0.17	0.49	-10000	0	-1.1	181	181
Tie2/SHP2	-0.086	0.26	-10000	0	-1.3	35	35
TEK	-0.095	0.3	-10000	0	-1.5	35	35
RPS6KB1	-0.1	0.38	-10000	0	-0.87	181	181
Angiotensin II/AT1	-0.16	0.27	-10000	0	-0.64	208	208
Tie2/Ang1/GRB2	-0.24	0.5	-10000	0	-1.2	181	181
MAPK3	-0.15	0.46	-10000	0	-1.1	181	181
MAPK1	-0.15	0.46	-10000	0	-1.1	181	181
Tie2/Ang1/GRB7	-0.24	0.5	-10000	0	-1.2	181	181
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.18	0.51	-10000	0	-1.2	181	181
PI3K	-0.14	0.46	-10000	0	-1	181	181
FES	-0.16	0.48	-10000	0	-1.1	181	181
Crk/Dok-R	-0.23	0.46	-10000	0	-1.1	181	181
Tie2/Ang1/ABIN2	-0.24	0.5	-10000	0	-1.2	181	181
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.088	0.36	-10000	0	-0.8	181	181
STAT5A	-0.006	0.072	-10000	0	-0.82	7	7
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.1	0.38	-10000	0	-0.87	181	181
Tie2/Ang2	-0.12	0.4	-10000	0	-0.93	143	143
Tie2/Ang1	-0.21	0.56	-10000	0	-1.3	181	181
FOXO1	-0.085	0.37	-10000	0	-0.81	181	181
ELF1	0.014	0.02	-10000	0	-10000	0	0
ELF2	-0.18	0.5	-10000	0	-1.2	181	181
mol:Choline	-0.16	0.48	-10000	0	-1.1	181	181
cell migration	-0.035	0.1	-10000	0	-0.25	51	51
FYN	-0.086	0.34	-10000	0	-0.77	143	143
DOK2	-0.003	0.043	-10000	0	-0.82	2	2
negative regulation of cell cycle	-0.045	0.25	-10000	0	-0.57	105	105
ETS1	-0.023	0.1	-10000	0	-1	2	2
PXN	-0.068	0.32	-10000	0	-0.71	181	181
ITGB1	0	0	-10000	0	-10000	0	0
NOS3	-0.074	0.34	-10000	0	-0.75	181	181
RAC1	0	0	-10000	0	-10000	0	0
TNF	-0.04	0.15	-10000	0	-0.84	17	17
MAPKKK cascade	-0.16	0.48	-10000	0	-1.1	181	181
RASA1	0	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.22	0.51	-10000	0	-1.2	181	181
NCK1	0	0	-10000	0	-10000	0	0
vasculogenesis	-0.045	0.27	-10000	0	-0.58	181	181
mol:Phosphatidic acid	-0.16	0.48	-10000	0	-1.1	181	181
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.057	0.3	-10000	0	-0.66	181	181
Rac1/GTP	-0.16	0.32	-10000	0	-0.8	181	181
MMP2	-0.18	0.51	-10000	0	-1.2	181	181

×

Endothelins

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.014	0.19	-9999	-0.6	75	75
PTK2B	0	0	-9999	-10000	0	0
mol:Ca2+	0.024	0.18	-9999	-0.93	20	20
EDN1	-0.042	0.25	-9999	-0.85	74	74
EDN3	-0.39	0.41	-9999	-0.82	429	429
EDN2	-0.074	0.14	-9999	-0.82	6	6
HRAS/GDP	-0.029	0.2	-9999	-0.52	80	80
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.004	0.14	-9999	-0.42	50	50
ADCY4	-0.15	0.29	-9999	-0.58	257	257
ADCY5	-0.28	0.37	-9999	-0.63	423	423
ADCY6	-0.14	0.27	-9999	-0.55	241	241
ADCY7	-0.14	0.27	-9999	-0.55	241	241
ADCY1	-0.15	0.29	-9999	-0.58	252	252
ADCY2	-0.17	0.32	-9999	-0.62	267	267
ADCY3	-0.14	0.27	-9999	-0.55	241	241
ADCY8	-0.14	0.27	-9999	-0.56	241	241
ADCY9	-0.14	0.27	-9999	-0.55	241	241
arachidonic acid secretion	-0.11	0.29	-9999	-0.46	306	306
ETB receptor/Endothelin-1/Gq/GTP	-0.033	0.17	-9999	-0.38	141	141
GNAO1	-0.034	0.14	-9999	-0.82	24	24
HRAS	-0.001	0.013	-9999	-0.28	2	2
ETA receptor/Endothelin-1/G12/GTP	0.034	0.2	-9999	-0.56	75	75
ETA receptor/Endothelin-1/Gs/GTP	-0.095	0.32	-9999	-0.59	241	241
mol:GTP	-0.001	0.006	-9999	-10000	0	0
COL3A1	-0.023	0.2	-9999	-0.6	75	75
EDNRB	-0.065	0.24	-9999	-0.82	81	81
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.025	0.23	-9999	-0.67	86	86
CYSLTR1	-0.023	0.22	-9999	-0.66	84	84
SLC9A1	0	0.1	-9999	-0.31	74	74
mol:GDP	-0.038	0.21	-9999	-0.55	85	85
SLC9A3	-0.047	0.27	-9999	-0.62	145	145
RAF1	-0.086	0.24	-9999	-0.53	137	137
JUN	0.026	0.18	-9999	-0.9	21	21
JAK2	-0.015	0.2	-9999	-0.6	75	75
mol:IP3	-0.029	0.17	-9999	-0.5	62	62
ETA receptor/Endothelin-1	0.03	0.25	-9999	-0.68	77	77
PLCB1	-0.053	0.2	-9999	-0.83	59	59
PLCB2	-0.001	0.029	-9999	-0.83	1	1
ETA receptor/Endothelin-3	-0.29	0.33	-9999	-0.64	427	427
FOS	-0.26	0.5	-9999	-0.99	290	290
Gai/GDP	-0.042	0.16	-9999	-0.69	35	35
CRK	0	0	-9999	-10000	0	0
mol:Ca ++	-0.05	0.24	-9999	-0.67	91	91
BCAR1	0.001	0.002	-9999	-10000	0	0
PRKCB1	-0.032	0.17	-9999	-0.46	72	72
GNAQ	0.007	0.04	-9999	-0.83	2	2
GNAZ	-0.007	0.077	-9999	-0.82	8	8
GNAL	-0.19	0.35	-9999	-0.82	210	210
Gs family/GDP	-0.17	0.26	-9999	-0.55	250	250
ETA receptor/Endothelin-1/Gq/GTP	0.015	0.13	-9999	-0.39	49	49
MAPK14	-0.03	0.17	-9999	-0.47	72	72
TRPC6	0.022	0.19	-9999	-1	20	20
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GNAI1	-0.042	0.18	-9999	-0.82	47	47
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.038	0.18	-9999	-0.43	111	111
ETB receptor/Endothelin-2	-0.1	0.2	-9999	-0.68	86	86
ETB receptor/Endothelin-3	-0.35	0.35	-9999	-0.68	469	469
ETB receptor/Endothelin-1	-0.082	0.27	-9999	-0.68	145	145
MAPK3	-0.2	0.41	-9999	-0.79	291	291
MAPK1	-0.2	0.41	-9999	-0.79	291	291
Rac1/GDP	-0.03	0.2	-9999	-0.52	80	80
cAMP biosynthetic process	-0.18	0.3	-9999	-0.61	254	254
MAPK8	0.022	0.16	-9999	-0.66	29	29
SRC	0	0.009	-9999	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.049	0.19	-9999	-0.42	133	133
p130Cas/CRK/Src/PYK2	-0.013	0.2	-9999	-0.58	60	60
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.03	0.2	-9999	-0.52	78	78
COL1A2	-0.054	0.25	-9999	-0.68	84	84
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.029	0.11	-9999	-0.63	6	6
mol:DAG	-0.029	0.17	-9999	-0.48	68	68
MAP2K2	-0.14	0.31	-9999	-0.56	296	296
MAP2K1	-0.14	0.31	-9999	-0.56	296	296
EDNRA	0.026	0.059	-9999	-0.31	2	2
positive regulation of muscle contraction	-0.013	0.17	-9999	-0.52	75	75
Gq family/GDP	-0.073	0.16	-9999	-0.6	44	44
HRAS/GTP	-0.052	0.2	-9999	-0.46	117	117
PRKCH	-0.023	0.17	-9999	-0.52	51	51
RAC1	0	0	-9999	-10000	0	0
PRKCA	-0.034	0.19	-9999	-0.58	64	64
PRKCB	-0.035	0.19	-9999	-0.62	48	48
PRKCE	-0.023	0.17	-9999	-0.52	52	52
PRKCD	-0.024	0.17	-9999	-0.53	48	48
PRKCG	-0.032	0.17	-9999	-0.54	50	50
regulation of vascular smooth muscle contraction	-0.31	0.57	-9999	-1.1	290	290
PRKCQ	-0.044	0.21	-9999	-0.58	81	81
PLA2G4A	-0.12	0.32	-9999	-0.51	306	306
GNA14	-0.005	0.089	-9999	-0.43	30	30
GNA15	0.006	0.037	-9999	-0.36	7	7
GNA12	0	0	-9999	-10000	0	0
GNA11	0.007	0.039	-9999	-0.82	2	2
Rac1/GTP	0.034	0.2	-9999	-0.56	75	75
MMP1	-0.12	0.12	-9999	-10000	0	0

×

EPHB forward signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.057	0.16	-10000	0	-0.56	89	89
cell-cell adhesion	0.19	0.22	0.71	63	-10000	0	63
Ephrin B/EPHB2/RasGAP	-0.041	0.13	-10000	0	-0.47	77	77
ITSN1	-0.002	0.039	-10000	0	-0.82	2	2
PIK3CA	0	0.009	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.002	0.016	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.23	0.27	-10000	0	-0.56	384	384
HRAS/GDP	-0.19	0.24	-10000	0	-0.43	402	402
Ephrin B/EPHB1/GRB7	-0.24	0.29	-10000	0	-0.54	403	403
Endophilin/SYNJ1	-0.039	0.12	-10000	0	-0.44	77	77
KRAS	0	0.009	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.24	0.29	-10000	0	-0.53	402	402
endothelial cell migration	-0.001	0.016	-10000	0	-0.47	1	1
GRB2	0	0.009	-10000	0	-10000	0	0
GRB7	-0.021	0.076	-10000	0	-0.82	1	1
PAK1	-0.048	0.14	-10000	0	-0.48	85	85
HRAS	-0.001	0.013	-10000	0	-0.28	2	2
RRAS	-0.039	0.12	-10000	0	-0.44	77	77
DNM1	-0.005	0.062	-10000	0	-0.73	6	6
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.22	0.27	-10000	0	-0.51	402	402
lamellipodium assembly	-0.19	0.22	-10000	0	-0.71	63	63
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.16	0.19	-10000	0	-0.37	384	384
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
EPHB2	-0.005	0.038	-10000	0	-10000	0	0
EPHB3	-0.003	0.029	-10000	0	-0.28	10	10
EPHB1	-0.35	0.41	-10000	0	-0.82	384	384
EPHB4	0	0.009	-10000	0	-0.28	1	1
mol:GDP	-0.17	0.22	-10000	0	-0.66	81	81
Ephrin B/EPHB2	-0.042	0.13	-10000	0	-0.48	77	77
Ephrin B/EPHB3	-0.041	0.13	-10000	0	-0.48	77	77
JNK cascade	-0.19	0.22	-10000	0	-0.46	384	384
Ephrin B/EPHB1	-0.24	0.29	-10000	0	-0.54	402	402
RAP1/GDP	-0.14	0.18	-10000	0	-0.57	77	77
EFNB2	0	0	-10000	0	-10000	0	0
EFNB3	-0.07	0.23	-10000	0	-0.82	77	77
EFNB1	0	0.009	-10000	0	-0.28	1	1
Ephrin B2/EPHB1-2	-0.22	0.25	-10000	0	-0.51	384	384
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.2	0.24	-10000	0	-0.71	80	80
Rap1/GTP	-0.19	0.23	-10000	0	-0.73	62	62
axon guidance	-0.057	0.16	-10000	0	-0.55	89	89
MAPK3	-0.11	0.19	-10000	0	-0.54	59	59
MAPK1	-0.11	0.19	-10000	0	-0.54	59	59
Rac1/GDP	-0.15	0.2	-10000	0	-0.6	78	78
actin cytoskeleton reorganization	-0.14	0.17	-10000	0	-0.55	62	62
CDC42/GDP	-0.15	0.2	-10000	0	-0.6	78	78
PI3K	-0.001	0.016	-10000	0	-0.47	1	1
EFNA5	-0.081	0.24	-10000	0	-0.82	89	89
Ephrin B2/EPHB4	0	0.005	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.03	0.1	-10000	0	-0.35	77	77
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.18	0.22	-10000	0	-0.7	63	63
PTK2	0.045	0.052	-10000	0	-10000	0	0
MAP4K4	-0.2	0.23	-10000	0	-0.46	384	384
SRC	0	0.009	-10000	0	-10000	0	0
KALRN	-0.014	0.11	-10000	0	-0.82	16	16
Intersectin/N-WASP	-0.001	0.03	-10000	0	-0.63	2	2
neuron projection morphogenesis	-0.15	0.18	-10000	0	-0.56	68	68
MAP2K1	-0.15	0.18	-10000	0	-0.57	60	60
WASL	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.21	0.25	-10000	0	-0.5	384	384
cell migration	-0.14	0.23	-10000	0	-0.56	82	82
NRAS	-0.001	0.013	-10000	0	-0.28	2	2
SYNJ1	-0.039	0.12	-10000	0	-0.44	77	77
PXN	0	0	-10000	0	-10000	0	0
TF	-0.26	0.28	-10000	0	-0.48	535	535
HRAS/GTP	-0.2	0.24	-10000	0	-0.46	402	402
Ephrin B1/EPHB1-2	-0.22	0.25	-10000	0	-0.51	384	384
cell adhesion mediated by integrin	0.007	0.14	0.44	77	-10000	0	77
RAC1	0	0	-10000	0	-10000	0	0
mol:GTP	-0.22	0.26	-10000	0	-0.49	402	402
RAC1-CDC42/GTP	-0.19	0.22	-10000	0	-0.72	63	63
RASA1	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.14	0.18	-10000	0	-0.57	77	77
ruffle organization	-0.19	0.23	-10000	0	-0.73	63	63
NCK1	0	0	-10000	0	-10000	0	0
receptor internalization	0.002	0.14	-10000	0	-0.44	78	78
Ephrin B/EPHB2/KALRN	-0.049	0.15	-10000	0	-0.51	85	85
ROCK1	-0.001	0.013	-10000	0	-10000	0	0
RAS family/GDP	-0.13	0.16	-10000	0	-0.54	60	60
Rac1/GTP	-0.2	0.24	-10000	0	-0.78	63	63
Ephrin B/EPHB1/Src/Paxillin	-0.17	0.21	-10000	0	-0.38	402	402

×

Wnt 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.17	0.26	-9999	-0.46	332	332
FZD6	-0.006	0.072	-9999	-0.82	7	7
WNT6	-0.17	0.33	-9999	-0.82	181	181
WNT4	-0.024	0.13	-9999	-0.82	20	20
FZD3	-0.009	0.086	-9999	-0.82	10	10
WNT5A	-0.013	0.094	-9999	-0.58	20	20
WNT11	-0.19	0.34	-9999	-0.82	203	203

×

Ephrin B reverse 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
EFNB2	0	0	-10000	0	-10000	0	0
EPHB2	-0.004	0.038	-10000	0	-10000	0	0
EFNB1	0.017	0.049	-10000	0	-0.64	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.18	0.22	-10000	0	-0.43	385	385
Ephrin B2/EPHB1-2	-0.21	0.25	-10000	0	-0.5	384	384
neuron projection morphogenesis	-0.18	0.21	-10000	0	-0.42	385	385
Ephrin B1/EPHB1-2/Tiam1	-0.2	0.23	-10000	0	-0.47	385	385
DNM1	-0.005	0.062	-10000	0	-0.74	6	6
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.003	0.13	-10000	0	-0.76	25	25
YES1	-0.023	0.16	-10000	0	-1	24	24
Ephrin B1/EPHB1-2/NCK2	-0.2	0.23	-10000	0	-0.47	385	385
PI3K	-0.021	0.13	-10000	0	-0.77	25	25
mol:GDP	-0.2	0.23	-10000	0	-0.46	385	385
ITGA2B	-0.016	0.076	-10000	0	-0.31	47	47
endothelial cell proliferation	0	0.005	-10000	0	-10000	0	0
FYN	-0.023	0.16	-10000	0	-1	24	24
MAP3K7	-0.021	0.13	-10000	0	-0.82	24	24
FGR	-0.025	0.16	-10000	0	-1	24	24
TIAM1	-0.001	0.018	-10000	0	-10000	0	0
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
RGS3	0	0	-10000	0	-10000	0	0
cell adhesion	-0.035	0.14	-10000	0	-0.63	44	44
LYN	-0.023	0.16	-10000	0	-1	24	24
Ephrin B1/EPHB1-2/Src Family Kinases	-0.024	0.15	-10000	0	-0.94	24	24
Ephrin B1/EPHB1-2	-0.028	0.14	-10000	0	-0.89	24	24
SRC	-0.025	0.16	-10000	0	-1	24	24
ITGB3	-0.018	0.12	-10000	0	-0.82	19	19
EPHB1	-0.35	0.41	-10000	0	-0.82	384	384
EPHB4	0	0.009	-10000	0	-0.28	1	1
RAC1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0.005	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.024	0.1	-10000	0	-0.64	22	22
BLK	-0.025	0.16	-10000	0	-1	24	24
HCK	-0.025	0.16	-10000	0	-1	24	24
regulation of stress fiber formation	0.2	0.23	0.46	385	-10000	0	385
MAPK8	0.004	0.13	-10000	0	-0.74	26	26
Ephrin B1/EPHB1-2/RGS3	-0.2	0.23	-10000	0	-0.47	385	385
endothelial cell migration	-0.015	0.12	-10000	0	-0.72	24	24
NCK2	0	0	-10000	0	-10000	0	0
PTPN13	-0.015	0.15	-10000	0	-0.94	24	24
regulation of focal adhesion formation	0.2	0.23	0.46	385	-10000	0	385
chemotaxis	0.2	0.23	0.46	385	-10000	0	385
PIK3CA	0	0.009	-10000	0	-10000	0	0
Rac1/GTP	-0.18	0.21	-10000	0	-0.42	385	385
angiogenesis	-0.027	0.14	-10000	0	-0.88	24	24
LCK	-0.027	0.16	-10000	0	-1	24	24

×

FOXM1 transcription factor network

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
NFATC3	-0.22	0.42	-9999	-0.97	99	99
PLK1	-0.079	0.098	-9999	-10000	0	0
BIRC5	-0.089	0.094	-9999	-10000	0	0
HSPA1B	-0.22	0.42	-9999	-0.93	120	120
MAP2K1	0.008	0.028	-9999	-10000	0	0
BRCA2	-0.22	0.42	-9999	-0.94	124	124
FOXM1	-0.27	0.49	-9999	-1	191	191
XRCC1	-0.22	0.42	-9999	-0.94	113	113
FOXM1B/p19	-0.27	0.4	-9999	-0.89	195	195
Cyclin D1/CDK4	-0.21	0.39	-9999	-0.88	120	120
CDC2	-0.24	0.44	-9999	-0.88	191	191
TGFA	-0.21	0.41	-9999	-0.9	129	129
SKP2	-0.22	0.42	-9999	-0.95	109	109
CCNE1	-0.051	0.12	-9999	-0.29	176	176
CKS1B	-0.22	0.42	-9999	-0.94	120	120
RB1	-0.11	0.12	-9999	-1	2	2
FOXM1C/SP1	-0.28	0.43	-9999	-0.91	200	200
AURKB	-0.071	0.099	-9999	-10000	0	0
CENPF	-0.25	0.44	-9999	-0.98	126	126
CDK4	0.007	0.018	-9999	-0.28	2	2
MYC	-0.2	0.4	-9999	-0.83	156	156
CHEK2	0.007	0.032	-9999	-0.3	2	2
ONECUT1	-0.22	0.41	-9999	-0.87	153	153
CDKN2A	-0.033	0.11	-9999	-10000	0	0
LAMA4	-0.22	0.42	-9999	-0.94	120	120
FOXM1B/HNF6	-0.25	0.46	-9999	-1	153	153
FOS	-0.44	0.68	-9999	-1.3	300	300
SP1	0	0	-9999	-10000	0	0
CDC25B	-0.22	0.42	-9999	-0.93	124	124
response to radiation	-0.007	0.029	-9999	-10000	0	0
CENPB	-0.22	0.42	-9999	-0.92	126	126
CENPA	-0.25	0.44	-9999	-0.9	180	180
NEK2	-0.27	0.43	-9999	-0.93	158	158
HIST1H2BA	-0.23	0.42	-9999	-0.93	127	127
CCNA2	-0.12	0.15	-9999	-0.29	389	389
EP300	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.26	0.46	-9999	-0.98	170	170
CCNB2	-0.25	0.44	-9999	-0.98	125	125
CCNB1	-0.24	0.44	-9999	-0.92	170	170
ETV5	-0.22	0.42	-9999	-0.95	113	113
ESR1	-0.32	0.56	-9999	-1.3	185	185
CCND1	-0.21	0.4	-9999	-0.88	128	128
GSK3A	0.013	0.02	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.08	0.13	-9999	-0.32	11	11
CDK2	0.005	0.008	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.009	0.035	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.31	0.36	-9999	-0.87	198	198
GAS1	-0.26	0.48	-9999	-1.1	145	145
MMP2	-0.22	0.43	-9999	-0.99	108	108
RB1/FOXM1C	-0.22	0.42	-9999	-0.93	128	128
CREBBP	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	0.23	-10000	0	-0.51	219	219
GRB2/SOS1/SHC	0	0.004	-10000	0	-10000	0	0
HRAS	-0.001	0.013	-10000	0	-0.28	2	2
IRS1/Crk	-0.12	0.24	-10000	0	-0.51	219	219
IGF-1R heterotetramer/IGF1/PTP1B	-0.13	0.24	-10000	0	-0.56	207	207
AKT1	-0.066	0.21	-10000	0	-0.43	207	207
BAD	-0.053	0.2	-10000	0	-0.69	33	33
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.12	0.23	-10000	0	-0.51	219	219
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.12	0.24	-10000	0	-0.51	219	219
RAF1	-0.046	0.19	-10000	0	-0.64	33	33
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.12	0.22	-10000	0	-0.48	219	219
YWHAZ	-0.001	0.016	-10000	0	-0.28	3	3
IGF-1R heterotetramer/IGF1/IRS1	-0.13	0.26	-10000	0	-0.55	219	219
PIK3CA	0	0.009	-10000	0	-10000	0	0
RPS6KB1	-0.066	0.21	-10000	0	-0.43	207	207
GNB2L1	0	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.039	0.16	-10000	0	-0.52	33	33
PXN	0	0	-10000	0	-10000	0	0
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
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	-0.43	208	208
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.1	0.2	-10000	0	-0.45	207	207
IGF-1R heterotetramer	-0.044	0.14	-10000	0	-0.66	33	33
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.12	0.24	-10000	0	-0.51	219	219
Crk/p130 Cas/Paxillin	-0.11	0.21	-10000	0	-0.46	207	207
IGF1R	-0.044	0.14	-10000	0	-0.66	33	33
IGF1	-0.18	0.35	-10000	0	-0.85	197	197
IRS2/Crk	-0.13	0.26	-10000	0	-0.53	230	230
PI3K	-0.11	0.22	-10000	0	-0.48	219	219
apoptosis	0.079	0.15	0.56	34	-10000	0	34
HRAS/GDP	0	0.009	-10000	0	-10000	0	0
PRKCD	-0.095	0.25	-10000	0	-0.55	207	207
RAF1/14-3-3 E	-0.074	0.14	-10000	0	-0.54	31	31
BAD/14-3-3	-0.084	0.16	-10000	0	-0.61	34	34
PRKCZ	-0.067	0.21	-10000	0	-0.43	207	207
Crk/p130 Cas/Paxillin/FAK1	-0.083	0.16	-10000	0	-0.64	31	31
PTPN1	-0.003	0.03	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.13	0.25	-10000	0	-0.58	207	207
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.11	0.21	-10000	0	-0.49	207	207
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	219	219
GRB10	0	0	-10000	0	-10000	0	0
PTPN11	-0.12	0.23	-10000	0	-0.51	219	219
IRS1	-0.13	0.25	-10000	0	-0.55	219	219
IRS2	-0.14	0.27	-10000	0	-0.56	230	230
IGF-1R heterotetramer/IGF1	-0.16	0.29	-10000	0	-0.69	207	207
GRB2	0	0.009	-10000	0	-10000	0	0
PDPK1	-0.11	0.21	-10000	0	-0.46	207	207
YWHAE	0	0	-10000	0	-10000	0	0
PRKD1	-0.11	0.28	-10000	0	-0.59	218	218
SHC1	0	0	-10000	0	-10000	0	0

×

IL23-mediated signaling events

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
CCL2	-0.17	0.4	-9999	-0.95	97	97
IL23A	-0.18	0.4	-9999	-1	79	79
NF kappa B1 p50/RelA/I kappa B alpha	-0.24	0.32	-9999	-0.87	130	130
positive regulation of T cell mediated cytotoxicity	-0.19	0.43	-9999	-0.86	208	208
ITGA3	-0.17	0.39	-9999	-1	80	80
IL17F	-0.1	0.29	-9999	-0.63	90	90
IL12B	-0.042	0.12	-9999	-0.27	176	176
STAT1 (dimer)	-0.22	0.38	-9999	-0.82	208	208
CD4	-0.16	0.38	-9999	-0.91	98	98
IL23	-0.18	0.38	-9999	-1	78	78
IL23R	-0.013	0.088	-9999	-10000	0	0
IL1B	-0.18	0.41	-9999	-1	101	101
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.17	0.39	-9999	-0.95	89	89
TYK2	0.011	0.016	-9999	-10000	0	0
STAT4	-0.033	0.16	-9999	-0.81	37	37
STAT3	0	0	-9999	-10000	0	0
IL18RAP	-0.031	0.16	-9999	-0.79	36	36
IL12RB1	0	0.064	-9999	-0.3	35	35
PIK3CA	0	0.009	-9999	-10000	0	0
IL12Rbeta1/TYK2	-0.003	0.048	-9999	-0.68	1	1
IL23R/JAK2	-0.011	0.11	-9999	-0.66	1	1
positive regulation of chronic inflammatory response	-0.19	0.43	-9999	-0.86	208	208
natural killer cell activation	0.002	0.008	-9999	-10000	0	0
JAK2	0.017	0.036	-9999	-0.86	1	1
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
NFKB1	0	0.001	-9999	-10000	0	0
RELA	0	0.001	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.17	0.38	-9999	-0.94	84	84
ALOX12B	-0.17	0.39	-9999	-0.97	80	80
CXCL1	-0.37	0.65	-9999	-1.4	254	254
T cell proliferation	-0.19	0.43	-9999	-0.86	208	208
NFKBIA	0	0.001	-9999	-10000	0	0
IL17A	-0.071	0.24	-9999	-0.51	69	69
PI3K	-0.25	0.33	-9999	-0.79	207	207
IFNG	-0.005	0.026	-9999	-0.09	26	26
STAT3 (dimer)	-0.24	0.32	-9999	-0.79	164	164
IL18R1	-0.011	0.094	-9999	-0.82	12	12
IL23/IL23R/JAK2/TYK2/SOCS3	-0.085	0.24	-9999	-0.56	55	55
IL18/IL18R	-0.031	0.12	-9999	-0.57	44	44
macrophage activation	-0.014	0.017	-9999	-0.041	113	113
TNF	-0.18	0.42	-9999	-1.1	84	84
STAT3/STAT4	-0.26	0.36	-9999	-0.82	218	218
STAT4 (dimer)	-0.24	0.4	-9999	-0.86	218	218
IL18	-0.007	0.043	-9999	-10000	0	0
IL19	-0.18	0.39	-9999	-0.91	108	108
STAT5A (dimer)	-0.23	0.38	-9999	-0.82	211	211
STAT1	-0.006	0.04	-9999	-0.28	19	19
SOCS3	-0.005	0.067	-9999	-0.82	6	6
CXCL9	-0.19	0.39	-9999	-0.94	108	108
MPO	-0.22	0.48	-9999	-1.1	148	148
positive regulation of humoral immune response	-0.19	0.43	-9999	-0.86	208	208
IL23/IL23R/JAK2/TYK2	-0.2	0.45	-9999	-0.89	208	208
IL6	-0.47	0.71	-9999	-1.4	344	344
STAT5A	-0.006	0.072	-9999	-0.82	7	7
IL2	0.003	0.029	-9999	-0.29	8	8
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.008	-9999	-10000	0	0
CD3E	-0.18	0.42	-9999	-0.97	118	118
keratinocyte proliferation	-0.19	0.43	-9999	-0.86	208	208
NOS2	-0.17	0.39	-9999	-0.89	119	119

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.11	0.21	-9999	-0.62	111	111
SMAD6-7/SMURF1	-0.001	0.018	-9999	-0.55	1	1
NOG	-0.023	0.13	-9999	-0.61	35	35
SMAD9	-0.1	0.26	-9999	-0.83	87	87
SMAD4	0	0	-9999	-10000	0	0
SMAD5	-0.079	0.18	-9999	-0.48	120	120
BMP7/USAG1	-0.36	0.36	-9999	-0.69	471	471
SMAD5/SKI	-0.09	0.16	-9999	-0.52	80	80
SMAD1	0.025	0.031	-9999	-10000	0	0
BMP2	-0.15	0.32	-9999	-0.82	164	164
SMAD1/SMAD1/SMAD4	-0.002	0.012	-9999	-10000	0	0
BMPR1A	-0.001	0.027	-9999	-0.82	1	1
BMPR1B	-0.14	0.18	-9999	-0.31	402	402
BMPR1A-1B/BAMBI	-0.092	0.15	-9999	-0.62	51	51
AHSG	-0.002	0.024	-9999	-10000	0	0
CER1	-0.001	0.013	-9999	-10000	0	0
BMP2-4/CER1	-0.14	0.26	-9999	-0.6	206	206
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.11	0.2	-9999	-0.61	87	87
BMP2-4 (homodimer)	-0.15	0.29	-9999	-0.68	206	206
RGMB	-0.001	0.027	-9999	-0.82	1	1
BMP6/BMPR2/BMPR1A-1B	-0.1	0.17	-9999	-0.56	96	96
RGMA	-0.11	0.28	-9999	-0.82	125	125
SMURF1	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.11	0.2	-9999	-0.63	90	90
BMP2-4/USAG1	-0.39	0.38	-9999	-0.68	528	528
SMAD6/SMURF1/SMAD5	-0.09	0.16	-9999	-0.52	80	80
SOSTDC1	-0.4	0.41	-9999	-0.82	450	450
BMP7/BMPR2/BMPR1A-1B	-0.1	0.17	-9999	-0.59	89	89
SKI	0	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.067	0.22	-9999	-0.81	76	76
HFE2	-0.002	0.024	-9999	-10000	0	0
ZFYVE16	0	0	-9999	-10000	0	0
MAP3K7	0	0.009	-9999	-10000	0	0
BMP2-4/CHRD	-0.15	0.28	-9999	-0.64	208	208
SMAD5/SMAD5/SMAD4	-0.09	0.16	-9999	-0.52	80	80
MAPK1	0	0	-9999	-10000	0	0
TAK1/TAB family	-0.089	0.17	-9999	-0.54	88	88
BMP7 (homodimer)	-0.076	0.22	-9999	-0.82	71	71
NUP214	0	0	-9999	-10000	0	0
BMP6/FETUA	-0.054	0.18	-9999	-0.64	74	74
SMAD1/SKI	-0.005	0.014	-9999	-10000	0	0
SMAD6	-0.001	0.027	-9999	-0.82	1	1
CTDSP2	0	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.14	0.26	-9999	-0.6	206	206
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.039	0.12	-9999	-0.33	109	109
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	-0.64	24	24
CHRDL1	-0.57	0.38	-9999	-0.82	632	632
ENDOFIN/SMAD1	-0.005	0.014	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.003	0.015	-9999	-10000	0	0
SMAD6/SMURF1	0	0	-9999	-10000	0	0
BAMBI	-0.035	0.15	-9999	-0.82	27	27
SMURF2	0	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.5	0.38	-9999	-0.7	648	648
BMP2-4/GREM1	-0.15	0.26	-9999	-0.61	209	209
SMAD7	0	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.093	0.24	-9999	-0.77	87	87
SMAD1/SMAD6	-0.005	0.014	-9999	-10000	0	0
TAK1/SMAD6	0	0.006	-9999	-10000	0	0
BMP7	-0.076	0.22	-9999	-0.82	71	71
BMP6	-0.067	0.22	-9999	-0.81	76	76
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.1	0.19	-9999	-0.61	87	87
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	0.25	-9999	-0.52	180	180
CHRD	-0.031	0.13	-9999	-0.42	67	67
BMPR2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.13	0.24	-9999	-0.55	170	170
BMP4	-0.054	0.2	-9999	-0.82	60	60
FST	-0.035	0.16	-9999	-0.78	41	41
BMP2-4/NOG	-0.15	0.27	-9999	-0.61	218	218
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.093	0.16	-9999	-0.56	89	89

×

Calcium signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.01	0.031	-9999	-0.54	1	1
NFATC2	-0.028	0.15	-9999	-0.58	61	61
NFATC3	0.011	0.025	-9999	-10000	0	0
CD40LG	-0.24	0.35	-9999	-0.73	254	254
PTGS2	-0.35	0.45	-9999	-0.87	357	357
JUNB	0	0.009	-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	-0.008	0.082	-9999	-0.83	9	9
mol:Ca2+	-0.006	0.009	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.005	-9999	-10000	0	0
FOSL1	-0.008	0.056	-9999	-0.82	2	2
CREM	0	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.067	0.14	-9999	-0.55	50	50
FOS	-0.26	0.39	-9999	-0.84	283	283
IFNG	-0.23	0.34	-9999	-0.69	260	260
AP-1/NFAT1-c-4	-0.31	0.38	-9999	-0.84	257	257
FASLG	-0.23	0.33	-9999	-0.69	248	248
NFAT1-c-4/ICER1	-0.048	0.13	-9999	-0.49	62	62
IL2RA	-0.23	0.34	-9999	-0.7	251	251
FKBP12/FK506	0	0.006	-9999	-10000	0	0
CSF2	-0.22	0.33	-9999	-0.69	249	249
JunB/Fra1/NFAT1-c-4	-0.045	0.12	-9999	-0.52	43	43
IL4	-0.21	0.34	-9999	-0.69	246	246
IL2	-0.011	0.024	-9999	-10000	0	0
IL3	-0.024	0.027	-9999	-10000	0	0
FKBP1A	0	0.009	-9999	-0.28	1	1
BATF3	-0.002	0.033	-9999	-0.39	5	5
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.001	0.01	-9999	-0.28	1	1

×

Neurotrophic factor-mediated Trk receptor signaling

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	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	74	74
NT3 (dimer)/TRKC	-0.32	0.38	-10000	0	-0.73	397	397
NT3 (dimer)/TRKB	-0.53	0.47	-10000	0	-0.83	583	583
SHC/Grb2/SOS1/GAB1/PI3K	0	0.011	-10000	0	-0.33	1	1
RAPGEF1	0	0	-10000	0	-10000	0	0
BDNF	-0.073	0.23	-10000	0	-0.82	74	74
PIK3CA	0	0.009	-10000	0	-10000	0	0
DYNLT1	0	0.009	-10000	0	-0.28	1	1
NTRK1	-0.01	0.065	-10000	0	-0.82	3	3
NTRK2	-0.43	0.41	-10000	0	-0.82	476	476
NTRK3	-0.29	0.39	-10000	0	-0.82	319	319
NT-4/5 (dimer)/TRKB	-0.63	0.52	-10000	0	-0.92	630	630
neuron apoptosis	0.25	0.25	0.6	263	-10000	0	263
SHC 2-3/Grb2	-0.28	0.28	-10000	0	-0.67	263	263
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.26	0.3	-10000	0	-0.69	249	249
SHC3	-0.26	0.28	-10000	0	-0.67	252	252
STAT3 (dimer)	-0.005	0.028	-10000	0	-0.38	3	3
NT3 (dimer)/TRKA	-0.27	0.34	-10000	0	-0.64	383	383
RIN/GDP	-0.072	0.13	-10000	0	-0.28	57	57
GIPC1	0	0.009	-10000	0	-10000	0	0
KRAS	0	0.009	-10000	0	-10000	0	0
DNAJA3	-0.15	0.21	-10000	0	-0.44	296	296
RIN/GTP	0	0.009	-10000	0	-10000	0	0
CCND1	0.018	0.072	-10000	0	-1	3	3
MAGED1	-0.001	0.013	-10000	0	-0.28	2	2
PTPN11	0	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.3	0.4	-10000	0	-0.82	338	338
SHC/GRB2/SOS1	0	0.004	-10000	0	-10000	0	0
GRB2	0	0.009	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.029	0.11	-10000	0	-0.57	35	35
TRKA/NEDD4-2	-0.007	0.05	-10000	0	-0.63	4	4
ELMO1	0	0	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0	0	-10000	0	-10000	0	0
NGF	-0.016	0.11	-10000	0	-0.65	22	22
HRAS	-0.001	0.013	-10000	0	-0.28	2	2
DOCK1	0	0	-10000	0	-10000	0	0
GAB2	-0.002	0.026	-10000	0	-10000	0	0
RIT2	-0.001	0.013	-10000	0	-10000	0	0
RIT1	0	0	-10000	0	-10000	0	0
FRS2	-0.003	0.029	-10000	0	-0.28	10	10
DNM1	-0.005	0.062	-10000	0	-0.73	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	-0.14	0.2	-10000	0	-0.43	296	296
mol:GDP	-0.11	0.19	-10000	0	-0.37	207	207
NGF (dimer)	-0.016	0.11	-10000	0	-0.65	22	22
RhoG/GDP	0	0	-10000	0	-10000	0	0
RIT1/GDP	-0.068	0.13	-10000	0	-0.26	99	99
TIAM1	-0.001	0.018	-10000	0	-10000	0	0
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
BDNF (dimer)/TRKB	-0.33	0.32	-10000	0	-0.6	500	500
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.001	0.014	-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	0.3	-10000	0	-0.82	149	149
RAP1/GDP	-0.077	0.087	-10000	0	-0.25	17	17
KIDINS220/CRKL	0	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.073	0.23	-10000	0	-0.82	74	74
ubiquitin-dependent protein catabolic process	-0.016	0.081	-10000	0	-0.55	19	19
Schwann cell development	-0.06	0.045	-10000	0	-10000	0	0
EHD4	0	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.001	0.012	-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	0.4	-10000	0	-0.88	367	367
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	0.028	-10000	0	-0.38	3	3
axon guidance	-0.42	0.37	-10000	0	-0.65	591	591
MAPK3	-0.026	0.1	-10000	0	-0.52	35	35
MAPK1	-0.026	0.1	-10000	0	-0.52	35	35
CDC42/GDP	-0.068	0.13	-10000	0	-0.26	99	99
NTF3	-0.14	0.3	-10000	0	-0.82	149	149
NTF4	-0.3	0.4	-10000	0	-0.82	338	338
NGF (dimer)/TRKA/FAIM	-0.015	0.079	-10000	0	-0.55	18	18
PI3K	-0.001	0.022	-10000	0	-0.63	1	1
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	-0.16	0.22	-10000	0	-0.46	305	305
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.26	0.35	-10000	0	-0.64	398	398
RGS19	-0.001	0.016	-10000	0	-0.28	3	3
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.006	0.083	-10000	0	-10000	0	0
Rac1/GDP	-0.068	0.13	-10000	0	-0.28	52	52
NGF (dimer)/TRKA/GRIT	-0.016	0.081	-10000	0	-0.56	18	18
neuron projection morphogenesis	-0.11	0.21	-10000	0	-0.41	294	294
NGF (dimer)/TRKA/NEDD4-2	-0.016	0.081	-10000	0	-0.55	19	19
MAP2K1	0	0.003	-10000	0	-10000	0	0
NGFR	-0.27	0.39	-10000	0	-0.82	296	296
NGF (dimer)/TRKA/GIPC/GAIP	-0.01	0.055	-10000	0	-0.35	22	22
RAS family/GTP/PI3K	-0.001	0.011	-10000	0	-0.34	1	1
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.01	-10000	0	-10000	0	0
NRAS	-0.001	0.013	-10000	0	-0.28	2	2
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
PRKCI	0	0.009	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	-0.001	0.027	-10000	0	-0.82	1	1
MAPKKK cascade	-0.067	0.12	-10000	0	-0.82	18	18
RASA1	0	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.007	0.046	-10000	0	-0.63	3	3
SQSTM1	-0.001	0.013	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.3	0.29	-10000	0	-0.55	500	500
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.013	0.068	-10000	0	-0.47	19	19
MATK	-0.023	0.12	-10000	0	-0.53	39	39
NEDD4L	-0.001	0.027	-10000	0	-0.82	1	1
RAS family/GDP	-0.069	0.082	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.16	0.22	-10000	0	-0.47	303	303
Rac1/GTP	-0.13	0.14	-10000	0	-0.35	227	227
FRS2 family/SHP2/CRK family	-0.001	0.01	-10000	0	-10000	0	0

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	-0.026	0.064	-10000	0	-0.52	2	2
epithelial cell differentiation	-0.02	0.055	-10000	0	-0.44	2	2
ITCH	0.009	0.021	-10000	0	-10000	0	0
WWP1	0.007	0.068	-10000	0	-10000	0	0
FYN	-0.001	0.027	-10000	0	-0.82	1	1
EGFR	-0.3	0.4	-10000	0	-0.82	331	331
PRL	-0.003	0.03	-10000	0	-0.28	11	11
neuron projection morphogenesis	-0.11	0.22	-10000	0	-0.49	56	56
PTPRZ1	-0.44	0.41	-10000	0	-0.82	479	479
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.17	0.21	-10000	0	-0.54	63	63
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.2	0.25	-10000	0	-0.52	332	332
ADAM17	0.009	0.021	-10000	0	-10000	0	0
ErbB4/ErbB4	0	0.086	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.061	0.14	-10000	0	-0.56	58	58
NCOR1	-0.001	0.027	-10000	0	-0.82	1	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.19	0.23	-10000	0	-0.49	332	332
GRIN2B	-0.2	0.25	-10000	0	-0.49	382	382
ErbB4/ErbB2/betacellulin	-0.049	0.12	-10000	0	-0.49	49	49
STAT1	-0.006	0.04	-10000	0	-0.28	19	19
HBEGF	-0.002	0.039	-10000	0	-0.82	2	2
PRLR	-0.003	0.035	-10000	0	-0.36	7	7
E4ICDs/ETO2	-0.036	0.095	-10000	0	-0.57	17	17
axon guidance	0.044	0.13	-10000	0	-0.39	1	1
NEDD4	0.009	0.021	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.004	0.032	-10000	0	-0.64	1	1
CBFA2T3	-0.017	0.11	-10000	0	-0.72	21	21
ErbB4/ErbB2/HBEGF	-0.025	0.052	-10000	0	-0.46	2	2
MAPK3	-0.16	0.2	-10000	0	-0.51	60	60
STAT1 (dimer)	-0.028	0.064	-10000	0	-10000	0	0
MAPK1	-0.16	0.2	-10000	0	-0.51	60	60
JAK2	-0.001	0.027	-10000	0	-0.82	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.2	0.23	-10000	0	-0.49	332	332
NRG1	-0.22	0.32	-10000	0	-0.64	332	332
NRG3	-0.059	0.2	-10000	0	-0.82	58	58
NRG2	-0.42	0.41	-10000	0	-0.82	461	461
NRG4	-0.005	0.037	-10000	0	-0.28	16	16
heart development	0.044	0.13	-10000	0	-0.39	1	1
neural crest cell migration	-0.19	0.23	-10000	0	-0.49	332	332
ERBB2	0.009	0.057	-10000	0	-10000	0	0
WWOX/E4ICDs	-0.025	0.059	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.2	0.22	-10000	0	-0.48	326	326
apoptosis	0.061	0.15	0.54	58	-10000	0	58
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.29	0.25	-10000	0	-0.53	461	461
ErbB4/ErbB2/epiregulin	-0.087	0.16	-10000	0	-0.48	108	108
ErbB4/ErbB4/betacellulin/betacellulin	-0.053	0.13	-10000	0	-0.53	49	49
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.019	0.057	-10000	0	-0.51	4	4
MDM2	0.009	0.075	-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	332	332
STAT5A	0.044	0.12	-10000	0	-0.49	4	4
ErbB4/EGFR/neuregulin 1 beta	-0.35	0.37	-10000	0	-0.69	455	455
DLG4	0	0	-10000	0	-10000	0	0
GRB2/SHC	0	0.006	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.024	0.056	-10000	0	-0.48	1	1
STAT5A (dimer)	-0.02	0.059	-10000	0	-0.48	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.022	0.066	-10000	0	-0.47	3	3
LRIG1	-0.001	0.027	-10000	0	-0.82	1	1
EREG	-0.12	0.27	-10000	0	-0.82	108	108
BTC	-0.045	0.19	-10000	0	-0.82	49	49
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.044	0.13	-10000	0	-0.39	1	1
ERBB4	-0.031	0.073	-10000	0	-10000	0	0
STAT5B	-0.003	0.047	-10000	0	-0.82	3	3
YAP1	-0.01	0.042	-10000	0	-0.66	3	3
GRB2	0	0.009	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.026	0.051	-10000	0	-10000	0	0
glial cell differentiation	0.024	0.056	0.48	1	-10000	0	1
WWOX	0	0.009	-10000	0	-0.28	1	1
cell proliferation	-0.12	0.24	-10000	0	-0.56	70	70

×

Aurora B 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	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	70	70
Aurora B/RasGAP/Survivin	-0.17	0.13	-9999	-10000	0	0
Chromosomal passenger complex/Cul3 protein complex	-0.15	0.15	-9999	-0.35	281	281
BIRC5	-0.2	0.13	-9999	-10000	0	0
DES	-0.3	0.34	-9999	-0.65	437	437
Aurora C/Aurora B/INCENP	-0.065	0.072	-9999	-0.64	1	1
Aurora B/TACC1	-0.091	0.12	-9999	-0.63	25	25
Aurora B/PP2A	-0.094	0.091	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.007	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	483	483
Cul3 protein complex	-0.22	0.27	-9999	-0.55	366	366
KIF2C	-0.036	0.026	-9999	-10000	0	0
PEBP1	0	0	-9999	-10000	0	0
KIF20A	-0.22	0.12	-9999	-0.28	261	261
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.094	0.091	-9999	-10000	0	0
SEPT1	-0.006	0.041	-9999	-10000	0	0
SMC2	0	0	-9999	-10000	0	0
SMC4	-0.005	0.035	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	0.012	0.015	-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	416	416
AURKC	-0.005	0.043	-9999	-0.32	14	14
CDCA8	-0.1	0.14	-9999	-0.28	330	330
cytokinesis	-0.1	0.068	-9999	-10000	0	0
Aurora B/Septin1	-0.087	0.078	-9999	-10000	0	0
AURKA	-0.14	0.14	-9999	-0.28	450	450
INCENP	0.001	0.004	-9999	-10000	0	0
KLHL13	-0.33	0.4	-9999	-0.82	365	365
BUB1	-0.2	0.13	-9999	-10000	0	0
hSgo1/Aurora B/Survivin	-0.25	0.17	-9999	-0.39	481	481
EVI5	0.007	0.005	-9999	-10000	0	0
RhoA/GTP	-0.093	0.092	-9999	-10000	0	0
SGOL1	-0.19	0.13	-9999	-0.28	613	613
CENPA	-0.049	0.054	-9999	-10000	0	0
NCAPG	-0.15	0.14	-9999	-0.28	497	497
Aurora B/HC8 Proteasome	-0.094	0.091	-9999	-10000	0	0
NCAPD2	-0.002	0.026	-9999	-10000	0	0
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	397	397
NPM1	-0.012	0.019	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
KLHL9	-0.002	0.039	-9999	-0.82	2	2
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	-0.34	16	16
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.012	0.019	-9999	-10000	0	0
MYLK	-0.077	0.14	-9999	-0.47	96	96
KIF23	-0.092	0.13	-9999	-10000	0	0
VIM	-0.091	0.1	-9999	-0.71	2	2
RACGAP1	-0.013	0.061	-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	0.063	-9999	-10000	0	0
Chromosomal passenger complex/EVI5	-0.15	0.17	-9999	-10000	0	0
TACC1	-0.023	0.14	-9999	-0.82	25	25
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

×

Visual signal transduction: Rods

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
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	-0.008	0.034	-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	-10000	0	0
GRK1	-0.003	0.029	-9999	-0.28	10	10
CNG Channel	-0.15	0.21	-9999	-0.46	276	276
mol:Na +	-0.14	0.2	-9999	-0.44	271	271
mol:ADP	-0.003	0.029	-9999	-0.28	10	10
RGS9-1/Gbeta5/R9AP	-0.067	0.17	-9999	-0.56	97	97
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.14	0.2	-9999	-0.45	271	271
CNGB1	-0.014	0.062	-9999	-0.28	47	47
RDH5	-0.52	0.4	-9999	-0.82	573	573
SAG	-0.014	0.061	-9999	-0.28	46	46
mol:Ca2+	-0.13	0.19	-9999	-0.42	270	270
Na + (4 Units)	-0.13	0.18	-9999	-0.41	270	270
RGS9	-0.091	0.26	-9999	-0.77	107	107
GNB1/GNGT1	-0.028	0.064	-9999	-10000	0	0
GNAT1/GDP	-0.059	0.15	-9999	-0.49	97	97
GUCY2D	-0.005	0.049	-9999	-0.36	13	13
GNGT1	-0.044	0.1	-9999	-0.28	144	144
GUCY2F	-0.001	0.013	-9999	-0.28	2	2
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.018	0.073	-9999	-0.48	19	19
mol:11-cis-retinal	-0.52	0.4	-9999	-0.82	573	573
mol:cGMP	-0.01	0.049	-9999	-0.48	7	7
GNB1	0	0	-9999	-10000	0	0
Rhodopsin	-0.4	0.31	-9999	-0.64	573	573
SLC24A1	0	0	-9999	-10000	0	0
CNGA1	-0.24	0.38	-9999	-0.82	272	272
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	-0.51	7	7
RGS9BP	-0.016	0.064	-9999	-0.28	51	51
Metarhodopsin II/Transducin	-0.008	0.018	-9999	-10000	0	0
GCAP Family/Ca ++	-0.009	0.046	-9999	-0.52	5	5
PDE6A/B	-0.017	0.094	-9999	-0.64	19	19
mol:Pi	-0.067	0.17	-9999	-0.56	97	97
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.021	0.047	-9999	-10000	0	0
PDE6B	-0.017	0.12	-9999	-0.8	20	20
PDE6A	-0.006	0.042	-9999	-0.28	21	21
PDE6G	-0.011	0.055	-9999	-10000	0	0
RHO	-0.004	0.034	-9999	-0.28	14	14
PDE6	-0.068	0.16	-9999	-0.47	112	112
GUCA1A	-0.012	0.058	-9999	-10000	0	0
GC2/GCAP Family	-0.009	0.046	-9999	-0.52	5	5
GUCA1C	0	0.009	-9999	-10000	0	0
GUCA1B	-0.005	0.061	-9999	-0.82	5	5

×

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

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.11	0.24	-10000	0	-0.63	154	154
CRKL	-0.04	0.16	-10000	0	-0.36	154	154
mol:PIP3	-0.017	0.039	0.81	2	-10000	0	2
AKT1	0.004	0.024	0.5	2	-10000	0	2
PTK2B	0	0	-10000	0	-10000	0	0
RAPGEF1	-0.031	0.15	-10000	0	-0.56	18	18
RANBP10	0	0	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-10000	0	0
HGF/MET/SHIP2	-0.13	0.25	-10000	0	-0.59	193	193
MAP3K5	-0.021	0.15	-10000	0	-0.54	20	20
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.12	0.23	-10000	0	-0.54	193	193
AP1	-0.2	0.28	-10000	0	-0.61	284	284
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	-0.24	0.37	-10000	0	-0.78	284	284
STAT3 (dimer)	-0.073	0.15	-10000	0	-0.34	193	193
GAB1/CRKL/SHP2/PI3K	-0.061	0.12	-10000	0	-0.52	19	19
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	-0.066	0.13	-10000	0	-0.56	18	18
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	0.039	-10000	0	-0.82	2	2
ELK1	-0.044	0.1	-10000	0	-0.28	154	154
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.046	0.095	-10000	0	-0.43	18	18
PAK1	0.009	0.029	0.46	2	-10000	0	2
HGF/MET/RANBP10	-0.13	0.25	-10000	0	-0.59	193	193
HRAS	-0.15	0.3	-10000	0	-0.71	193	193
DOCK1	-0.031	0.15	-10000	0	-0.56	18	18
GAB1	-0.051	0.17	-10000	0	-0.36	193	193
CRK	-0.04	0.16	-10000	0	-0.36	154	154
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.15	0.31	-10000	0	-0.73	193	193
JUN	-0.008	0.081	-10000	0	-0.82	9	9
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.078	0.16	-10000	0	-0.37	193	193
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
cell morphogenesis	-0.015	0.17	-10000	0	-0.6	18	18
GRB2/SHC	-0.067	0.14	-10000	0	-0.34	154	154
FOS	-0.26	0.38	-10000	0	-0.82	283	283
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.044	0.1	-10000	0	-0.28	154	154
HGF/MET/MUC20	-0.13	0.26	-10000	0	-0.6	193	193
cell migration	-0.066	0.13	-10000	0	-0.34	154	154
GRB2	0	0.009	-10000	0	-10000	0	0
CBL	0	0	-10000	0	-10000	0	0
MET/RANBP10	-0.11	0.24	-10000	0	-0.63	154	154
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.077	0.16	-10000	0	-0.36	193	193
MET/MUC20	-0.11	0.24	-10000	0	-0.64	154	154
RAP1B	-0.021	0.14	-10000	0	-0.51	18	18
RAP1A	-0.021	0.14	-10000	0	-0.51	18	18
HGF/MET/RANBP9	-0.13	0.25	-10000	0	-0.59	193	193
RAF1	-0.1	0.3	-10000	0	-0.73	154	154
STAT3	-0.073	0.15	-10000	0	-0.35	193	193
cell proliferation	-0.061	0.23	-10000	0	-0.5	193	193
RPS6KB1	-0.027	0.053	-10000	0	-10000	0	0
MAPK3	-0.044	0.094	-10000	0	-0.25	154	154
MAPK1	-0.044	0.094	-10000	0	-0.25	154	154
RANBP9	0	0	-10000	0	-10000	0	0
MAPK8	0	0.13	-10000	0	-0.43	22	22
SRC	-0.071	0.14	-10000	0	-0.63	18	18
PI3K	-0.067	0.14	-10000	0	-0.34	155	155
MET/Glomulin	-0.098	0.22	-10000	0	-0.58	154	154
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	-0.086	0.27	-10000	0	-0.66	154	154
MET	-0.14	0.31	-10000	0	-0.82	155	155
MAP4K1	-0.03	0.15	-10000	0	-0.56	20	20
PTK2	0	0	-10000	0	-10000	0	0
MAP2K2	-0.086	0.27	-10000	0	-0.66	154	154
BAD	0.011	0.022	0.46	2	-10000	0	2
MAP2K4	-0.011	0.14	-10000	0	-0.47	21	21
SHP2/GRB2/SOS1/GAB1	-0.098	0.2	-10000	0	-0.52	154	154
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	-0.071	0.14	-10000	0	-0.36	154	154
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.051	0.2	-10000	0	-0.82	57	57
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	154	154
PDPK1	-0.006	0.028	0.58	2	-10000	0	2
HGF/MET/SHIP	-0.13	0.25	-10000	0	-0.59	193	193

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.062	0.17	-10000	0	-0.51	110	110
regulation of S phase of mitotic cell cycle	-0.039	0.11	-10000	0	-0.34	104	104
GNAO1	-0.034	0.14	-10000	0	-0.83	24	24
HRAS	-0.001	0.013	-10000	0	-0.28	2	2
SHBG/T-DHT	0	0	-10000	0	-10000	0	0
PELP1	0	0	-10000	0	-10000	0	0
AKT1	0.011	0.001	-10000	0	-10000	0	0
MAP2K1	-0.04	0.16	-10000	0	-0.45	104	104
T-DHT/AR	-0.074	0.21	-10000	0	-0.65	104	104
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.004	-10000	0	-0.007	283	283
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.042	0.18	-10000	0	-0.83	47	47
mol:GDP	-0.071	0.2	-10000	0	-0.63	104	104
cell proliferation	-0.1	0.24	-10000	0	-0.57	88	88
PIK3CA	0	0.009	-10000	0	-10000	0	0
FOS	-0.24	0.43	-10000	0	-0.87	283	283
mol:Ca2+	-0.016	0.028	-10000	0	-0.078	121	121
MAPK3	-0.073	0.2	-10000	0	-0.62	52	52
MAPK1	-0.047	0.12	-10000	0	-0.31	52	52
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
mol:IP3	-0.001	0.002	-10000	0	-0.005	283	283
cAMP biosynthetic process	0.012	0.024	-10000	0	-10000	0	0
GNG2	-0.006	0.072	-10000	0	-0.82	7	7
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.005	283	283
HRAS/GTP	-0.062	0.15	-10000	0	-0.48	104	104
actin cytoskeleton reorganization	-0.001	0.015	-10000	0	-0.45	1	1
SRC	0	0.009	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.005	283	283
PI3K	-0.001	0.019	-10000	0	-0.56	1	1
apoptosis	0.11	0.23	0.43	283	-10000	0	283
T-DHT/AR/PELP1	-0.064	0.18	-10000	0	-0.56	104	104
HRAS/GDP	-0.068	0.19	-10000	0	-0.59	104	104
CREB1	-0.12	0.25	-10000	0	-0.46	283	283
RAC1-CDC42/GTP	-0.001	0.015	-10000	0	-0.45	1	1
AR	-0.095	0.26	-10000	0	-0.83	104	104
GNB1	0	0	-10000	0	-10000	0	0
RAF1	-0.04	0.16	-10000	0	-0.47	104	104
RAC1-CDC42/GDP	-0.064	0.18	-10000	0	-0.56	104	104
T-DHT/AR/PELP1/Src	-0.059	0.16	-10000	0	-0.52	104	104
MAP2K2	-0.04	0.16	-10000	0	-0.45	104	104
T-DHT/AR/PELP1/Src/PI3K	-0.039	0.11	-10000	0	-0.35	104	104
GNAZ	-0.007	0.077	-10000	0	-0.82	8	8
SHBG	0	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.037	0.1	-10000	0	-0.47	33	33
mol:T-DHT	-0.001	0.001	0.002	51	-0.003	231	282
RAC1	0	0	-10000	0	-10000	0	0
GNRH1	0.004	0.068	-10000	0	-0.64	10	10
Gi family/GTP	-0.048	0.1	-10000	0	-0.31	78	78
CDC42	0	0	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.055	0.21	-9999	-0.82	61	61
GNB1/GNG2	-0.15	0.24	-9999	-0.71	94	94
mol:DAG	-0.13	0.21	-9999	-0.62	94	94
PLCG1	-0.14	0.22	-9999	-0.66	94	94
YES1	-0.16	0.24	-9999	-0.69	100	100
FZD3	-0.009	0.086	-9999	-0.82	10	10
FZD6	-0.006	0.072	-9999	-0.82	7	7
G protein	-0.14	0.22	-9999	-0.66	95	95
MAP3K7	-0.074	0.19	-9999	-0.5	93	93
mol:Ca2+	-0.13	0.2	-9999	-0.6	94	94
mol:IP3	-0.13	0.21	-9999	-0.62	94	94
NLK	-0.006	0.01	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
CAMK2A	-0.088	0.21	-9999	-0.55	94	94
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.17	0.26	-9999	-0.46	332	332
CSNK1A1	0	0	-9999	-10000	0	0
GNAS	-0.16	0.24	-9999	-0.69	101	101
GO:0007205	-0.1	0.22	-9999	-0.61	94	94
WNT6	-0.17	0.33	-9999	-0.82	181	181
WNT4	-0.024	0.13	-9999	-0.82	20	20
NFAT1/CK1 alpha	-0.16	0.23	-9999	-0.64	119	119
GNG2	-0.006	0.072	-9999	-0.82	7	7
WNT5A	-0.013	0.094	-9999	-0.58	20	20
WNT11	-0.19	0.34	-9999	-0.82	203	203
CDC42	-0.12	0.24	-9999	-0.68	90	90

×

Syndecan-1-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
TGFB1	0	0.009	-9999	-0.28	1	1
CCL5	-0.014	0.078	-9999	-0.36	35	35
SDCBP	0	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.074	0.11	-9999	-0.34	91	91
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.068	0.099	-9999	-0.36	37	37
Syndecan-1/Syntenin	-0.068	0.099	-9999	-0.36	37	37
MAPK3	-0.051	0.09	-9999	-0.49	5	5
HGF/MET	-0.14	0.29	-9999	-0.68	193	193
TGFB1/TGF beta receptor Type II	0	0.009	-9999	-0.28	1	1
BSG	0	0	-9999	-10000	0	0
keratinocyte migration	-0.067	0.098	-9999	-0.35	37	37
Syndecan-1/RANTES	-0.074	0.11	-9999	-0.4	40	40
Syndecan-1/CD147	-0.059	0.096	-9999	-0.52	5	5
Syndecan-1/Syntenin/PIP2	-0.065	0.095	-9999	-0.34	37	37
LAMA5	0	0.009	-9999	-0.28	1	1
positive regulation of cell-cell adhesion	-0.064	0.094	-9999	-0.34	37	37
MMP7	-0.12	0.29	-9999	-0.73	155	155
HGF	-0.051	0.2	-9999	-0.82	57	57
Syndecan-1/CASK	-0.07	0.1	-9999	-0.33	91	91
Syndecan-1/HGF/MET	-0.17	0.26	-9999	-0.61	195	195
regulation of cell adhesion	-0.037	0.093	-9999	-0.5	4	4
HPSE	-0.007	0.054	-9999	-0.33	20	20
positive regulation of cell migration	-0.074	0.11	-9999	-0.34	91	91
SDC1	-0.074	0.11	-9999	-0.35	91	91
Syndecan-1/Collagen	-0.074	0.11	-9999	-0.34	91	91
PPIB	-0.001	0.016	-9999	-0.28	3	3
MET	-0.14	0.31	-9999	-0.82	155	155
PRKACA	0	0	-9999	-10000	0	0
MMP9	-0.13	0.14	-9999	-0.28	411	411
MAPK1	-0.051	0.09	-9999	-0.49	5	5
homophilic cell adhesion	-0.073	0.11	-9999	-0.34	91	91
MMP1	-0.21	0.12	-9999	-0.28	702	702

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.23	0.28	-10000	0	-0.56	376	376
fibroblast growth factor receptor signaling pathway	-0.23	0.27	-10000	0	-0.55	376	376
LAMA1	-0.096	0.26	-10000	0	-0.82	106	106
PRNP	-0.011	0.094	-10000	0	-0.82	12	12
GPC1/SLIT2	-0.057	0.18	-10000	0	-0.63	81	81
SMAD2	-0.017	0.089	-10000	0	-0.5	30	30
GPC1/PrPc/Cu2+	-0.008	0.066	-10000	0	-0.56	13	13
GPC1/Laminin alpha1	-0.075	0.2	-10000	0	-0.63	107	107
TDGF1	-0.009	0.086	-10000	0	-0.82	10	10
CRIPTO/GPC1	-0.008	0.07	-10000	0	-0.63	11	11
APP/GPC1	-0.001	0.023	-10000	0	-0.63	1	1
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.017	0.066	-10000	0	-0.55	12	12
FLT1	-0.001	0.027	-10000	0	-0.82	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.019	0.098	-10000	0	-0.55	30	30
SERPINC1	-0.013	0.06	-10000	0	-10000	0	0
FYN	0.017	0.066	-10000	0	-0.55	12	12
FGR	0.017	0.066	-10000	0	-0.55	12	12
positive regulation of MAPKKK cascade	0.03	0.077	-10000	0	-0.54	12	12
SLIT2	-0.072	0.23	-10000	0	-0.82	80	80
GPC1/NRG	-0.23	0.3	-10000	0	-0.63	333	333
NRG1	-0.3	0.4	-10000	0	-0.82	336	336
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.003	0.03	-10000	0	-0.55	2	2
LYN	0.018	0.063	-10000	0	-0.55	11	11
mol:Spermine	0.01	0.024	-10000	0	-0.64	1	1
cell growth	-0.23	0.27	-10000	0	-0.55	376	376
BMP signaling pathway	0.002	0.032	0.82	1	-10000	0	1
SRC	0.018	0.063	-10000	0	-0.55	11	11
TGFBR1	0	0.009	-10000	0	-0.28	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.28	0.39	-10000	0	-0.82	306	306
GPC1	-0.002	0.032	-10000	0	-0.82	1	1
TGFBR1 (dimer)	0	0.009	-10000	0	-0.28	1	1
VEGFA	-0.003	0.028	-10000	0	-0.28	9	9
BLK	-0.006	0.09	-10000	0	-0.58	13	13
HCK	0.016	0.066	-10000	0	-0.55	11	11
FGF2	-0.33	0.4	-10000	0	-0.82	370	370
FGFR1	-0.01	0.087	-10000	0	-0.73	12	12
VEGFR1 homodimer	-0.001	0.027	-10000	0	-0.82	1	1
TGFBR2	-0.026	0.14	-10000	0	-0.82	29	29
cell death	-0.001	0.023	-10000	0	-0.63	1	1
ATIII/GPC1	-0.01	0.044	-10000	0	-0.64	1	1
PLA2G2A/GPC1	-0.22	0.3	-10000	0	-0.64	306	306
LCK	0.006	0.093	-10000	0	-0.56	22	22
neuron differentiation	-0.23	0.3	-10000	0	-0.63	333	333
PrPc/Cu2+	-0.008	0.073	-10000	0	-0.64	12	12
APP	0	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	-0.026	0.14	-10000	0	-0.82	29	29

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.035	0.051	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.08	0.16	-9999	-0.48	76	76
JUN	-0.05	0.15	-9999	-0.57	21	21
HRAS	-0.001	0.013	-9999	-0.28	2	2
RET51/GFRalpha1/GDNF/GRB10	-0.15	0.21	-9999	-0.55	169	169
RAP1A	0	0	-9999	-10000	0	0
FRS2	-0.003	0.029	-9999	-0.28	10	10
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.15	0.21	-9999	-0.55	169	169
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	160	160
RHOA	0	0	-9999	-10000	0	0
RAP1A/GTP	-0.13	0.19	-9999	-0.5	166	166
GRB7	-0.021	0.076	-9999	-0.82	1	1
RET51/GFRalpha1/GDNF	-0.15	0.21	-9999	-0.55	169	169
MAPKKK cascade	-0.097	0.17	-9999	-0.56	41	41
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.12	0.24	-9999	-0.59	169	169
lamellipodium assembly	-0.079	0.15	-9999	-0.37	166	166
RET51/GFRalpha1/GDNF/SHC	-0.15	0.21	-9999	-0.55	169	169
PIK3CA	0	0.009	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.1	0.19	-9999	-0.52	160	160
RET9/GFRalpha1/GDNF/Shank3	-0.1	0.19	-9999	-0.52	160	160
MAPK3	-0.12	0.18	-9999	-0.47	166	166
DOK1	0	0.009	-9999	-10000	0	0
DOK6	-0.01	0.084	-9999	-0.82	9	9
PXN	0	0	-9999	-10000	0	0
neurite development	-0.11	0.16	-9999	-0.56	44	44
DOK5	-0.017	0.11	-9999	-0.7	22	22
GFRA1	-0.16	0.31	-9999	-0.68	215	215
MAPK8	-0.073	0.14	-9999	-0.48	29	29
HRAS/GTP	-0.1	0.2	-9999	-0.51	166	166
tube development	-0.096	0.18	-9999	-0.48	160	160
MAPK1	-0.12	0.18	-9999	-0.47	166	166
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.064	0.13	-9999	-0.34	160	160
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0	0.009	-9999	-10000	0	0
PDLIM7	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.15	0.2	-9999	-0.53	171	171
SHC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.15	0.21	-9999	-0.55	169	169
RET51/GFRalpha1/GDNF/Dok5	-0.16	0.22	-9999	-0.57	182	182
PRKCA	-0.02	0.12	-9999	-0.78	23	23
HRAS/GDP	0	0.009	-9999	-10000	0	0
CREB1	-0.071	0.15	-9999	-0.39	160	160
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.064	0.13	-9999	-0.34	160	160
RET51/GFRalpha1/GDNF/Grb7	-0.16	0.22	-9999	-0.57	171	171
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.12	0.16	-9999	-0.82	15	15
DOK4	0	0	-9999	-10000	0	0
JNK cascade	-0.049	0.14	-9999	-0.55	21	21
RET9/GFRalpha1/GDNF/FRS2	-0.1	0.19	-9999	-0.52	160	160
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	-0.064	0.13	-9999	-0.35	160	160
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.081	0.14	-9999	-0.37	166	166
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.081	0.14	-9999	-0.46	40	40
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.083	0.15	-9999	-0.38	166	166
PI3K	-0.13	0.25	-9999	-0.6	168	168
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.096	0.18	-9999	-0.48	160	160
GRB10	0	0	-9999	-10000	0	0
activation of MAPKK activity	-0.077	0.13	-9999	-0.35	160	160
RET51/GFRalpha1/GDNF/FRS2	-0.16	0.21	-9999	-0.55	169	169
GAB1	0	0	-9999	-10000	0	0
IRS1	-0.033	0.16	-9999	-0.82	36	36
IRS2	-0.034	0.16	-9999	-0.82	38	38
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.083	0.15	-9999	-0.38	166	166
RET51/GFRalpha1/GDNF/PKC alpha	-0.16	0.22	-9999	-0.56	190	190
GRB2	0	0.009	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GDNF	-0.016	0.064	-9999	-0.28	51	51
RAC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.17	0.25	-9999	-0.63	177	177
Rac1/GTP	-0.096	0.18	-9999	-0.46	166	166
RET9/GFRalpha1/GDNF	-0.12	0.21	-9999	-0.56	164	164
GFRalpha1/GDNF	-0.13	0.24	-9999	-0.64	164	164

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.63	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	531	531
AURKC	-0.005	0.043	-9999	-0.32	14	14

×

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	-0.096	0.18	-10000	0	-0.49	158	158
ER alpha/Gai/GDP/Gbeta gamma	-0.089	0.19	-10000	0	-0.48	151	151
AKT1	-0.12	0.3	-10000	0	-0.85	131	131
PIK3CA	0	0.009	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.12	0.3	-10000	0	-0.86	131	131
mol:Ca2+	-0.026	0.15	-10000	0	-0.48	68	68
IGF1R	-0.022	0.12	-10000	0	-0.61	33	33
E2/ER alpha (dimer)/Striatin	-0.1	0.2	-10000	0	-0.56	136	136
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	0.085	0.3	0.81	131	-10000	0	131
RhoA/GTP	-0.07	0.14	-10000	0	-0.42	131	131
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.089	0.21	-10000	0	-0.56	137	137
regulation of stress fiber formation	0.017	0.14	0.52	4	-10000	0	4
E2/ERA-ERB (dimer)	-0.11	0.21	-10000	0	-0.56	152	152
KRAS	0	0.009	-10000	0	-10000	0	0
G13/GTP	-0.09	0.18	-10000	0	-0.51	131	131
pseudopodium formation	-0.017	0.14	-10000	0	-0.52	4	4
E2/ER alpha (dimer)/PELP1	-0.098	0.19	-10000	0	-0.56	131	131
GRB2	0	0.009	-10000	0	-10000	0	0
GNG2	-0.006	0.072	-10000	0	-0.82	7	7
GNAO1	-0.034	0.14	-10000	0	-0.82	24	24
HRAS	-0.001	0.013	-10000	0	-0.28	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.057	0.22	-10000	0	-0.55	138	138
E2/ER beta (dimer)	-0.015	0.098	-10000	0	-0.64	22	22
mol:GDP	-0.085	0.21	-10000	0	-0.55	152	152
mol:NADP	-0.057	0.22	-10000	0	-0.55	138	138
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
mol:IP3	-0.028	0.15	-10000	0	-0.5	68	68
IGF-1R heterotetramer	-0.022	0.12	-10000	0	-0.61	33	33
PLCB1	-0.062	0.14	-10000	0	-0.52	67	67
PLCB2	-0.034	0.092	-10000	0	-0.65	12	12
IGF1	-0.18	0.34	-10000	0	-0.82	197	197
mol:L-citrulline	-0.057	0.22	-10000	0	-0.55	138	138
RHOA	0	0	-10000	0	-10000	0	0
Gai/GDP	-0.04	0.16	-10000	0	-0.86	24	24
JNK cascade	-0.015	0.098	-10000	0	-0.64	22	22
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	-0.02	0.13	-10000	0	-0.82	22	22
GNAQ	-0.002	0.039	-10000	0	-0.82	2	2
ESR1	-0.15	0.29	-10000	0	-0.57	248	248
Gq family/GDP/Gbeta gamma	-0.006	0.072	-10000	0	-0.74	6	6
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.023	0.13	-10000	0	-0.36	14	14
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.089	0.21	-10000	0	-0.56	137	137
GNAZ	-0.007	0.077	-10000	0	-0.82	8	8
E2/ER alpha (dimer)	-0.12	0.22	-10000	0	-0.64	131	131
STRN	-0.006	0.072	-10000	0	-0.82	7	7
GNAL	-0.19	0.35	-10000	0	-0.82	210	210
PELP1	0	0	-10000	0	-10000	0	0
MAPK11	0.003	0.094	-10000	0	-0.58	23	23
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.042	0.18	-10000	0	-0.82	47	47
HBEGF	-0.067	0.19	-10000	0	-0.45	142	142
cAMP biosynthetic process	-0.19	0.26	-10000	0	-0.53	319	319
SRC	-0.049	0.2	-10000	0	-0.46	140	140
PI3K	-0.001	0.022	-10000	0	-0.63	1	1
GNB1	0	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.076	0.19	-10000	0	-0.49	143	143
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.15	0.23	-10000	0	-0.52	205	205
Gs family/GTP	-0.2	0.27	-10000	0	-0.54	319	319
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.009	-10000	0	-10000	0	0
vasodilation	-0.053	0.21	-10000	0	-0.52	138	138
mol:DAG	-0.028	0.15	-10000	0	-0.5	68	68
Gs family/GDP/Gbeta gamma	-0.16	0.23	-10000	0	-0.52	193	193
MSN	-0.02	0.14	-10000	0	-0.58	4	4
Gq family/GTP	-0.037	0.096	-10000	0	-0.69	11	11
mol:PI-3-4-5-P3	-0.09	0.3	-10000	0	-0.82	131	131
NRAS	-0.001	0.013	-10000	0	-0.28	2	2
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.053	0.21	0.52	138	-10000	0	138
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
RhoA/GDP	-0.078	0.2	-10000	0	-0.51	152	152
NOS3	-0.061	0.23	-10000	0	-0.59	137	137
GNA11	-0.002	0.039	-10000	0	-0.82	2	2
MAPKKK cascade	-0.059	0.25	-10000	0	-0.65	136	136
E2/ER alpha (dimer)/PELP1/Src	-0.094	0.22	-10000	0	-0.59	137	137
ruffle organization	-0.017	0.14	-10000	0	-0.52	4	4
ROCK2	-0.068	0.14	-10000	0	-0.39	139	139
GNA14	-0.014	0.087	-10000	0	-0.42	30	30
GNA15	-0.003	0.035	-10000	0	-0.36	7	7
GNA13	0	0	-10000	0	-10000	0	0
MMP9	-0.093	0.2	-10000	0	-0.49	145	145
MMP2	-0.041	0.19	-10000	0	-0.68	27	27

×

IL6-mediated signaling events

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
BCL2L1	-0.056	0.22	-9999	-0.63	46	46
CRP	-0.06	0.22	-9999	-0.63	46	46
cell cycle arrest	-0.074	0.24	-9999	-0.71	53	53
TIMP1	-0.055	0.2	-9999	-0.56	48	48
IL6ST	-0.059	0.24	-9999	-0.82	79	79
Rac1/GDP	-0.14	0.2	-9999	-0.66	64	64
AP1	-0.14	0.24	-9999	-0.5	239	239
GAB2	-0.002	0.026	-9999	-10000	0	0
TNFSF11	-0.066	0.22	-9999	-0.63	46	46
HSP90B1	0.017	0.047	-9999	-10000	0	0
GAB1	0	0.002	-9999	-10000	0	0
MAPK14	-0.12	0.24	-9999	-0.74	67	67
AKT1	0.04	0.027	-9999	-10000	0	0
FOXO1	0.05	0.049	-9999	-0.43	8	8
MAP2K6	-0.14	0.25	-9999	-0.67	91	91
mol:GTP	0	0.001	-9999	-10000	0	0
MAP2K4	-0.076	0.22	-9999	-0.64	61	61
MITF	-0.13	0.25	-9999	-0.48	169	169
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0	0	-9999	-10000	0	0
A2M	0.015	0.11	-9999	-1.5	5	5
CEBPB	0.015	0.007	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.052	0.07	-9999	-10000	0	0
STAT3	-0.081	0.26	-9999	-0.77	54	54
STAT1	-0.012	0.023	-9999	-10000	0	0
CEBPD	-0.058	0.22	-9999	-0.66	46	46
PIK3CA	0.01	0.01	-9999	-10000	0	0
PI3K	-0.001	0.022	-9999	-0.63	1	1
JUN	-0.008	0.082	-9999	-0.82	9	9
PIAS3/MITF	-0.15	0.21	-9999	-0.67	66	66
MAPK11	-0.12	0.24	-9999	-0.75	67	67
STAT3 (dimer)/FOXO1	-0.024	0.22	-9999	-0.57	53	53
GRB2/SOS1/GAB family	-0.13	0.19	-9999	-0.75	42	42
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.15	0.24	-9999	-0.44	234	234
GRB2	0	0.009	-9999	-10000	0	0
JAK2	-0.001	0.027	-9999	-0.82	1	1
LBP	-0.23	0.45	-9999	-0.96	226	226
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
JAK1	0	0.002	-9999	-10000	0	0
MYC	-0.07	0.26	-9999	-0.8	56	56
FGG	-0.065	0.22	-9999	-0.63	48	48
macrophage differentiation	-0.074	0.24	-9999	-0.71	53	53
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.22	0.28	-9999	-0.51	398	398
JUNB	-0.055	0.21	-9999	-0.61	46	46
FOS	-0.26	0.38	-9999	-0.83	283	283
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.14	0.25	-9999	-0.46	231	231
STAT1/PIAS1	-0.14	0.2	-9999	-0.57	91	91
GRB2/SOS1/GAB family/SHP2/PI3K	0.001	0.013	-9999	-10000	0	0
STAT3 (dimer)	-0.076	0.25	-9999	-0.75	53	53
PRKCD	-0.052	0.22	-9999	-0.6	59	59
IL6R	-0.022	0.13	-9999	-0.82	25	25
SOCS3	-0.12	0.24	-9999	-0.79	58	58
gp130 (dimer)/JAK1/JAK1/LMO4	-0.04	0.16	-9999	-0.55	82	82
Rac1/GTP	-0.14	0.2	-9999	-0.64	69	69
HCK	-0.004	0.032	-9999	-0.28	12	12
MAPKKK cascade	-0.001	0.069	-9999	-10000	0	0
bone resorption	-0.062	0.21	-9999	-0.6	47	47
IRF1	-0.057	0.22	-9999	-0.62	50	50
mol:GDP	-0.12	0.24	-9999	-0.47	169	169
SOS1	0	0.002	-9999	-10000	0	0
VAV1	-0.12	0.24	-9999	-0.48	169	169
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.16	0.23	-9999	-0.8	63	63
PTPN11	-0.013	0.02	-9999	-10000	0	0
IL6/IL6RA	-0.25	0.32	-9999	-0.65	349	349
gp130 (dimer)/TYK2/TYK2/LMO4	-0.043	0.16	-9999	-0.55	82	82
gp130 (dimer)/JAK2/JAK2/LMO4	-0.044	0.16	-9999	-0.55	82	82
IL6	-0.3	0.4	-9999	-0.82	338	338
PIAS3	0	0	-9999	-10000	0	0
PTPRE	0.002	0.028	-9999	-0.83	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	-0.4	397	397
LMO4	0.008	0.054	-9999	-0.82	3	3
STAT3 (dimer)/PIAS3	-0.14	0.2	-9999	-0.77	53	53
MCL1	0.053	0.016	-9999	-10000	0	0

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.023	0.061	-9999	-0.59	8	8
alphaM/beta2 Integrin/GPIbA	-0.025	0.062	-9999	-0.57	8	8
alphaM/beta2 Integrin/proMMP-9	-0.081	0.079	-9999	-0.42	5	5
PLAUR	-0.021	0.073	-9999	-0.28	68	68
HMGB1	-0.014	0.018	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.018	0.028	-9999	-10000	0	0
AGER	-0.015	0.044	-9999	-0.88	2	2
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	-0.076	0.099	-9999	-0.72	2	2
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.13	0.14	-9999	-0.28	411	411
CYR61	-0.046	0.19	-9999	-0.82	51	51
TLN1	0	0	-9999	-10000	0	0
Rap1/GTP	-0.058	0.11	-9999	-0.54	20	20
RHOA	0	0	-9999	-10000	0	0
P-selectin oligomer	-0.2	0.35	-9999	-0.82	217	217
MYH2	-0.07	0.17	-9999	-0.43	84	84
MST1R	-0.01	0.085	-9999	-0.59	16	16
leukocyte activation during inflammatory response	-0.32	0.23	-9999	-0.49	586	586
APOB	-0.53	0.4	-9999	-0.82	586	586
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.007	0.077	-9999	-0.82	8	8
JAM3	-0.004	0.054	-9999	-0.82	4	4
GP1BA	-0.013	0.083	-9999	-0.82	7	7
alphaM/beta2 Integrin/CTGF	-0.025	0.07	-9999	-0.61	11	11
alphaM/beta2 Integrin	-0.073	0.14	-9999	-0.37	84	84
JAM3 homodimer	-0.004	0.054	-9999	-0.82	4	4
ICAM2	-0.005	0.061	-9999	-0.82	5	5
ICAM1	-0.004	0.032	-9999	-0.28	12	12
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.062	0.14	-9999	-0.3	173	173
cell adhesion	-0.025	0.062	-9999	-0.57	8	8
NFKB1	-0.14	0.18	-9999	-0.66	14	14
THY1	-0.002	0.022	-9999	-0.28	6	6
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.36	0.27	-9999	-0.56	586	586
alphaM/beta2 Integrin/LRP/tPA	-0.034	0.11	-9999	-0.57	36	36
IL6	-0.32	0.49	-9999	-0.96	338	338
ITGB2	-0.017	0.036	-9999	-0.31	5	5
elevation of cytosolic calcium ion concentration	-0.025	0.048	-9999	-0.38	1	1
alphaM/beta2 Integrin/JAM2/JAM3	-0.041	0.13	-9999	-0.55	50	50
JAM2	-0.043	0.18	-9999	-0.82	48	48
alphaM/beta2 Integrin/ICAM1	-0.022	0.083	-9999	-0.54	19	19
alphaM/beta2 Integrin/uPA/Plg	-0.02	0.033	-9999	-10000	0	0
RhoA/GTP	-0.087	0.17	-9999	-0.39	183	183
positive regulation of phagocytosis	-0.05	0.092	-9999	-0.47	17	17
Ron/MSP	-0.016	0.1	-9999	-0.69	19	19
alphaM/beta2 Integrin/uPAR/uPA	-0.025	0.048	-9999	-0.38	1	1
alphaM/beta2 Integrin/uPAR	-0.028	0.045	-9999	-0.42	1	1
PLAU	-0.009	0.048	-9999	-10000	0	0
PLAT	-0.027	0.14	-9999	-0.77	32	32
actin filament polymerization	-0.067	0.16	-9999	-0.4	94	94
MST1	-0.011	0.095	-9999	-0.75	14	14
alphaM/beta2 Integrin/lipoprotein(a)	-0.33	0.23	-9999	-0.5	586	586
TNF	-0.093	0.23	-9999	-0.97	18	18
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.022	0.037	-9999	-10000	0	0
fibrinolysis	-0.02	0.033	-9999	-10000	0	0
HCK	-0.004	0.032	-9999	-0.28	12	12
dendritic cell antigen processing and presentation	-0.062	0.14	-9999	-0.3	173	173
VTN	-0.023	0.092	-9999	-0.32	67	67
alphaM/beta2 Integrin/CYR61	-0.049	0.14	-9999	-0.6	51	51
LPA	-0.001	0.018	-9999	-0.28	4	4
LRP1	-0.009	0.086	-9999	-0.82	10	10
cell migration	-0.07	0.081	-9999	-0.54	9	9
FN1	-0.12	0.14	-9999	-10000	0	0
alphaM/beta2 Integrin/Thy1	-0.019	0.03	-9999	-10000	0	0
MPO	-0.057	0.21	-9999	-0.81	65	65
KNG1	-0.004	0.032	-9999	-0.28	12	12
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.065	0.17	-9999	-0.4	109	109
ELA2	0	0	-9999	-10000	0	0
PLG	-0.001	0.018	-9999	-0.28	4	4
CTGF	-0.011	0.091	-9999	-0.74	13	13
alphaM/beta2 Integrin/Hck	-0.02	0.034	-9999	-10000	0	0
ITGAM	-0.015	0.029	-9999	-0.34	2	2
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.13	0.22	-9999	-0.53	217	217
HP	-0.16	0.32	-9999	-0.74	200	200
leukocyte adhesion	-0.075	0.13	-9999	-0.6	32	32
SELP	-0.2	0.35	-9999	-0.82	217	217

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.018	0.031	-9999	-10000	0	0
VDR	0	0	-9999	-10000	0	0
FAM120B	0	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.041	0.17	-9999	-0.32	233	233
RXRs/LXRs/DNA/Oxysterols	-0.02	0.15	-9999	-0.5	17	17
MED1	-0.007	0.044	-9999	-0.28	23	23
mol:9cRA	0.005	0.008	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.02	0.086	-9999	-0.37	48	48
RXRs/NUR77	-0.17	0.26	-9999	-0.53	289	289
RXRs/PPAR	-0.14	0.23	-9999	-0.39	378	378
NCOR2	0	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0	0	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	-0.007	0.051	-9999	-0.47	10	10
RARA	-0.004	0.033	-9999	-10000	0	0
NCOA1	-0.001	0.027	-9999	-0.82	1	1
VDR/VDR/DNA	0	0	-9999	-10000	0	0
RARs/RARs/DNA/9cRA	-0.007	0.051	-9999	-0.48	10	10
RARG	0	0	-9999	-10000	0	0
RPS6KB1	0.031	0.054	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.019	0.081	-9999	-0.35	48	48
THRA	-0.001	0.027	-9999	-0.82	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	-0.13	0.22	-9999	-0.49	232	232
NR1H4	-0.002	0.024	-9999	-10000	0	0
RXRs/LXRs/DNA	-0.12	0.2	-9999	-0.45	232	232
NR1H2	0.016	0.006	-9999	-10000	0	0
NR1H3	0.016	0.007	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.12	0.2	-9999	-0.46	232	232
NR4A1	-0.074	0.24	-9999	-0.82	82	82
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.048	0.14	-9999	-0.28	232	232
RXRG	-0.2	0.36	-9999	-0.82	232	232
RXR alpha/CCPG	0	0	-9999	-10000	0	0
RXRA	0.016	0.006	-9999	-10000	0	0
RXRB	0.015	0.007	-9999	-10000	0	0
THRB	-0.036	0.17	-9999	-0.82	40	40
PPARG	-0.19	0.35	-9999	-0.82	209	209
PPARD	0	0	-9999	-10000	0	0
TNF	-0.023	0.2	-9999	-1.3	14	14
mol:Oxysterols	0.005	0.007	-9999	-10000	0	0
cholesterol transport	-0.019	0.15	-9999	-0.43	28	28
PPARA	-0.003	0.047	-9999	-0.82	3	3
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.009	0.086	-9999	-0.82	10	10
RXRs/NUR77/BCL2	-0.13	0.2	-9999	-0.39	306	306
SREBF1	-0.01	0.14	-9999	-0.68	5	5
RXRs/RXRs/DNA/9cRA	-0.13	0.22	-9999	-0.49	232	232
ABCA1	-0.012	0.16	-9999	-0.96	8	8
RARs/THRs	-0.027	0.11	-9999	-0.5	48	48
RXRs/FXR	-0.13	0.22	-9999	-0.5	232	232
BCL2	-0.027	0.15	-9999	-0.82	30	30

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.003	0.034	-9999	-0.63	2	2
alphaV beta3 Integrin	-0.23	0.28	-9999	-0.56	377	377
PTK2	-0.088	0.19	-9999	-0.67	24	24
IGF1R	-0.022	0.12	-9999	-0.61	33	33
PI4KB	0	0	-9999	-10000	0	0
MFGE8	-0.012	0.093	-9999	-0.63	17	17
SRC	0	0.009	-9999	-10000	0	0
CDKN1B	-0.088	0.12	-9999	-0.89	8	8
VEGFA	-0.003	0.028	-9999	-0.28	9	9
ILK	-0.085	0.11	-9999	-0.78	5	5
ROCK1	0	0	-9999	-10000	0	0
AKT1	-0.075	0.098	-9999	-0.73	5	5
PTK2B	-0.012	0.073	-9999	-0.48	20	20
alphaV/beta3 Integrin/JAM-A	-0.21	0.25	-9999	-0.49	380	380
CBL	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.013	0.08	-9999	-0.55	19	19
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.14	0.26	-9999	-0.57	219	219
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.008	0.046	-9999	-0.43	2	2
alphaV/beta3 Integrin/Syndecan-1	-0.022	0.087	-9999	-0.56	20	20
PI4KA	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.34	0.36	-9999	-0.73	337	337
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.049	0.098	-9999	-0.57	19	19
RPS6KB1	-0.31	0.33	-9999	-0.71	292	292
TLN1	0	0	-9999	-10000	0	0
MAPK3	-0.34	0.39	-9999	-0.78	377	377
GPR124	-0.007	0.077	-9999	-0.82	8	8
MAPK1	-0.34	0.39	-9999	-0.78	377	377
PXN	0	0	-9999	-10000	0	0
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
alphaV/beta3 Integrin/Tumstatin	-0.12	0.23	-9999	-0.56	192	192
cell adhesion	-0.018	0.093	-9999	-0.51	29	29
ANGPTL3	-0.002	0.021	-9999	-0.28	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	-0.003	0.029	-9999	-0.55	2	2
IGF-1R heterotetramer	-0.022	0.12	-9999	-0.61	33	33
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	-0.026	0.14	-9999	-0.82	29	29
ITGB3	-0.018	0.12	-9999	-0.82	19	19
IGF1	-0.18	0.34	-9999	-0.82	197	197
RAC1	0	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.017	0.1	-9999	-0.61	24	24
apoptosis	0	0	-9999	-10000	0	0
CD47	-0.001	0.027	-9999	-0.82	1	1
alphaV/beta3 Integrin/CD47	-0.013	0.081	-9999	-0.55	20	20
VCL	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.034	0.15	-9999	-0.69	42	42
CSF1	-0.005	0.067	-9999	-0.82	6	6
PIK3C2A	-0.085	0.11	-9999	-0.78	5	5
PI4 Kinase/Pyk2	-0.17	0.21	-9999	-0.59	51	51
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.013	0.079	-9999	-0.52	20	20
FAK1/Vinculin	-0.065	0.15	-9999	-0.51	23	23
alphaV beta3/Integrin/ppsTEM5	-0.017	0.1	-9999	-0.61	24	24
RHOA	0	0	-9999	-10000	0	0
VTN	-0.023	0.092	-9999	-0.32	67	67
BCAR1	0	0	-9999	-10000	0	0
FGF2	-0.33	0.4	-9999	-0.82	370	370
F11R	-0.24	0.32	-9999	-0.63	370	370
alphaV/beta3 Integrin/Lactadherin	-0.019	0.1	-9999	-0.58	28	28
alphaV/beta3 Integrin/TGFBR2	-0.029	0.14	-9999	-0.65	40	40
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.003	0.04	-9999	-0.5	6	6
HSP90AA1	0	0.009	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.011	0.073	-9999	-0.51	19	19
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.12	0.14	-9999	-10000	0	0
alphaV/beta3 Integrin/Pyk2	-0.012	0.074	-9999	-0.49	20	20
SDC1	-0.02	0.076	-9999	-0.82	1	1
VAV3	-0.008	0.054	-9999	-0.46	12	12
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.033	0.16	-9999	-0.82	36	36
FAK1/Paxillin	-0.065	0.15	-9999	-0.51	23	23
cell migration	-0.051	0.14	-9999	-0.45	23	23
ITGAV	0	0	-9999	-10000	0	0
PI3K	-0.19	0.22	-9999	-0.44	381	381
SPP1	-0.077	0.12	-9999	-0.28	254	254
KDR	-0.002	0.039	-9999	-0.82	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	-0.16	0.32	-9999	-0.81	180	180
angiogenesis	-0.3	0.39	-9999	-0.75	379	379
Rac1/GTP	-0.007	0.049	-9999	-0.42	12	12
EDIL3	-0.036	0.16	-9999	-0.82	35	35
cell proliferation	-0.029	0.14	-9999	-0.64	40	40

×

Signaling events mediated by PTP1B

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.002	0.039	-10000	0	-0.82	2	2
Jak2/Leptin Receptor	-0.16	0.24	-10000	0	-0.54	234	234
PTP1B/AKT1	-0.067	0.098	-10000	0	-0.32	88	88
FYN	-0.001	0.027	-10000	0	-0.82	1	1
p210 bcr-abl/PTP1B	-0.068	0.12	-10000	0	-0.37	93	93
EGFR	-0.3	0.4	-10000	0	-0.83	331	331
EGF/EGFR	-0.3	0.32	-10000	0	-0.59	453	453
CSF1	-0.005	0.067	-10000	0	-0.82	6	6
AKT1	0	0	-10000	0	-10000	0	0
INSR	0	0.009	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.092	0.12	-10000	0	-0.36	92	92
Insulin Receptor/Insulin	-0.047	0.072	-10000	0	-0.39	8	8
HCK	-0.004	0.032	-10000	0	-0.28	12	12
CRK	0	0	-10000	0	-10000	0	0
TYK2	-0.057	0.12	-10000	0	-0.35	90	90
EGF	-0.17	0.33	-10000	0	-0.83	183	183
YES1	-0.001	0.027	-10000	0	-0.82	1	1
CAV1	-0.17	0.24	-10000	0	-0.51	235	235
TXN	0	0.013	-10000	0	-0.29	1	1
PTP1B/IRS1/GRB2	-0.084	0.14	-10000	0	-0.5	57	57
cell migration	0.068	0.12	0.37	93	-10000	0	93
STAT3	0	0	-10000	0	-10000	0	0
PRLR	-0.001	0.036	-10000	0	-0.36	7	7
ITGA2B	-0.016	0.076	-10000	0	-0.32	46	46
CSF1R	-0.001	0.029	-10000	0	-0.55	2	2
Prolactin Receptor/Prolactin	-0.003	0.033	-10000	0	-0.64	1	1
FGR	-0.001	0.029	-10000	0	-0.82	1	1
PTP1B/p130 Cas	-0.072	0.11	-10000	0	-0.35	89	89
Crk/p130 Cas	-0.066	0.1	-10000	0	-0.41	24	24
DOK1	-0.043	0.1	-10000	0	-0.37	26	26
JAK2	-0.039	0.073	-10000	0	-0.33	10	10
Jak2/Leptin Receptor/Leptin	-0.38	0.19	-10000	0	-0.51	461	461
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
PTPN1	-0.069	0.12	-10000	0	-0.37	93	93
LYN	0	0	-10000	0	-10000	0	0
CDH2	-0.054	0.12	-10000	0	-0.82	2	2
SRC	-0.013	0.045	-10000	0	-10000	0	0
ITGB3	-0.018	0.12	-10000	0	-0.83	19	19
CAT1/PTP1B	-0.084	0.17	-10000	0	-0.44	81	81
CAPN1	0	0.002	-10000	0	-10000	0	0
CSK	0	0	-10000	0	-10000	0	0
PI3K	-0.037	0.066	-10000	0	-0.45	3	3
mol:H2O2	-0.006	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.33	0.16	-10000	0	-0.45	453	453
negative regulation of transcription	-0.039	0.072	-10000	0	-0.33	10	10
FCGR2A	0	0.009	-10000	0	-10000	0	0
FER	-0.005	0.068	-10000	0	-0.84	6	6
alphaIIb/beta3 Integrin	-0.025	0.1	-10000	0	-0.64	22	22
BLK	-0.039	0.1	-10000	0	-0.82	3	3
Insulin Receptor/Insulin/Shc	0	0.005	-10000	0	-10000	0	0
RHOA	0	0.002	-10000	0	-10000	0	0
LEPR	-0.2	0.36	-10000	0	-0.83	232	232
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0	0.009	-10000	0	-10000	0	0
mol:NADPH	-0.005	0.005	-10000	0	-10000	0	0
TRPV6	-0.034	0.13	-10000	0	-0.47	17	17
PRL	-0.003	0.031	-10000	0	-0.28	11	11
SOCS3	0.015	0.12	-10000	0	-1.5	6	6
SPRY2	-0.092	0.26	-10000	0	-0.84	101	101
Insulin Receptor/Insulin/IRS1	-0.022	0.11	-10000	0	-0.56	36	36
CSF1/CSF1R	-0.069	0.11	-10000	0	-0.36	79	79
Ras protein signal transduction	0.036	0.035	-10000	0	-10000	0	0
IRS1	-0.033	0.16	-10000	0	-0.82	36	36
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.67	0.32	-10000	0	-0.83	740	740
STAT5B	-0.056	0.1	-10000	0	-0.3	92	92
STAT5A	-0.056	0.1	-10000	0	-0.3	94	94
GRB2	0	0.009	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.073	0.11	-10000	0	-0.36	91	91
CSN2	0.019	0.03	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-10000	0	0
LAT	-0.014	0.053	-10000	0	-0.58	2	2
YBX1	-0.001	0.014	-10000	0	-10000	0	0
LCK	-0.018	0.1	-10000	0	-0.43	39	39
SHC1	0	0	-10000	0	-10000	0	0
NOX4	-0.003	0.038	-10000	0	-0.84	1	1

×

Ephrin A reverse signaling

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
MAPKKK cascade	-0.055	0.17	-9999	-0.56	89	89
EFNA5	-0.081	0.24	-9999	-0.82	89	89
FYN	-0.051	0.15	-9999	-0.51	89	89
neuron projection morphogenesis	-0.055	0.17	-9999	-0.56	89	89
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.055	0.17	-9999	-0.56	89	89
EPHA5	-0.001	0.018	-9999	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.003	0.028	-9999	-0.28	9	9
Syndecan-3/Src/Cortactin	-0.19	0.21	-9999	-0.43	403	403
Syndecan-3/Neurocan	-0.007	0.026	-9999	-10000	0	0
POMC	-0.024	0.12	-9999	-0.48	45	45
EGFR	-0.3	0.4	-9999	-0.82	331	331
Syndecan-3/EGFR	-0.17	0.22	-9999	-0.47	326	326
AGRP	-0.002	0.026	-9999	-10000	0	0
NCSTN	0	0	-9999	-10000	0	0
PSENEN	0	0.009	-9999	-0.28	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	-0.001	0.027	-9999	-0.82	1	1
APH1A	0	0	-9999	-10000	0	0
NCAN	-0.019	0.07	-9999	-0.28	61	61
long-term memory	-0.001	0.017	-9999	-0.44	1	1
Syndecan-3/IL8	-0.016	0.069	-9999	-0.47	18	18
PSEN1	0	0	-9999	-10000	0	0
Src/Cortactin	-0.002	0.018	-9999	-10000	0	0
FYN	-0.001	0.027	-9999	-0.82	1	1
limb bud formation	0	0.003	-9999	-10000	0	0
MC4R	-0.003	0.03	-9999	-10000	0	0
SRC	0	0.009	-9999	-10000	0	0
PTN	-0.36	0.41	-9999	-0.82	404	404
FGFR/FGF/Syndecan-3	0	0.003	-9999	-10000	0	0
neuron projection morphogenesis	-0.19	0.21	-9999	-0.42	403	403
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	0.027	-9999	-0.63	1	1
SDC3	0	0.003	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.016	0.068	-9999	-0.46	18	18
IL8	-0.034	0.13	-9999	-0.41	77	77
Syndecan-3/Fyn/Cortactin	-0.001	0.017	-9999	-0.45	1	1
Syndecan-3/CASK	0	0.003	-9999	-10000	0	0
alpha-MSH/MC4R	-0.02	0.093	-9999	-0.62	18	18
Gamma Secretase	-0.001	0.016	-9999	-0.47	1	1

×

LPA receptor mediated events

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
GNB1/GNG2	-0.014	0.086	-9999	-0.56	19	19
NF kappa B1 p50/RelA/I kappa B alpha	-0.046	0.12	-9999	-0.42	11	11
AP1	-0.2	0.27	-9999	-0.5	361	361
mol:PIP3	-0.2	0.25	-9999	-0.48	371	371
AKT1	-0.009	0.057	-9999	-0.58	3	3
PTK2B	0.015	0.059	-9999	-0.31	16	16
RHOA	0.029	0.025	-9999	-10000	0	0
PIK3CB	0	0	-9999	-10000	0	0
mol:Ca2+	-0.01	0.14	-9999	-0.37	111	111
MAGI3	-0.001	0.027	-9999	-0.82	1	1
RELA	0	0	-9999	-10000	0	0
apoptosis	-0.063	0.15	-9999	-0.43	128	128
HRAS/GDP	0	0.009	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.019	0.15	-9999	-0.43	96	96
NF kappa B1 p50/RelA	-0.054	0.14	-9999	-0.53	16	16
endothelial cell migration	0.011	0.11	-9999	-0.66	22	22
ADCY4	-0.001	0.15	-9999	-0.66	29	29
ADCY5	-0.069	0.19	-9999	-0.62	59	59
ADCY6	0.009	0.12	-9999	-0.63	21	21
ADCY7	0.009	0.12	-9999	-0.63	21	21
ADCY1	0.001	0.13	-9999	-0.63	25	25
ADCY2	-0.011	0.15	-9999	-0.63	34	34
ADCY3	0.009	0.12	-9999	-0.63	21	21
ADCY8	0.006	0.12	-9999	-0.64	21	21
ADCY9	0.009	0.12	-9999	-0.63	21	21
GSK3B	0.022	0.056	-9999	-0.36	7	7
arachidonic acid secretion	0.013	0.12	-9999	-0.46	42	42
GNG2	-0.006	0.072	-9999	-0.82	7	7
TRIP6	-0.001	0.018	-9999	-0.53	1	1
GNAO1	-0.006	0.13	-9999	-0.55	43	43
HRAS	-0.001	0.013	-9999	-0.28	2	2
NFKBIA	-0.006	0.16	-9999	-0.41	111	111
GAB1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.001	0.031	-9999	-0.95	1	1
JUN	-0.008	0.081	-9999	-0.82	9	9
LPA/LPA2/NHERF2	-0.001	0.012	-9999	-10000	0	0
TIAM1	-0.001	0.038	-9999	-1.1	1	1
PIK3R1	-0.001	0.027	-9999	-0.83	1	1
mol:IP3	-0.01	0.14	-9999	-0.37	111	111
PLCB3	-0.001	0.01	-9999	-10000	0	0
FOS	-0.26	0.38	-9999	-0.82	283	283
positive regulation of mitosis	0.013	0.12	-9999	-0.46	42	42
LPA/LPA1-2-3	-0.075	0.18	-9999	-0.52	121	121
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	-0.41	15	15
GNAZ	0.011	0.095	-9999	-0.5	29	29
EGFR/PI3K-beta/Gab1	-0.21	0.27	-9999	-0.5	371	371
positive regulation of dendritic cell cytokine production	-0.074	0.18	-9999	-0.51	121	121
LPA/LPA2/MAGI-3	-0.002	0.021	-9999	-0.55	1	1
ARHGEF1	-0.009	0.06	-9999	-0.46	14	14
GNAI2	0.016	0.076	-9999	-0.46	22	22
GNAI3	0.016	0.076	-9999	-0.46	22	22
GNAI1	-0.013	0.16	-9999	-0.57	62	62
LPA/LPA3	-0.085	0.21	-9999	-0.64	111	111
LPA/LPA2	-0.002	0.015	-9999	-10000	0	0
LPA/LPA1	-0.013	0.084	-9999	-0.54	22	22
HB-EGF/EGFR	-0.26	0.27	-9999	-0.6	326	326
HBEGF	-0.069	0.1	-9999	-0.64	3	3
mol:DAG	-0.01	0.14	-9999	-0.37	111	111
cAMP biosynthetic process	-0.01	0.15	-9999	-0.57	43	43
NFKB1	0	0	-9999	-10000	0	0
SRC	0	0.009	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
LYN	-0.006	0.16	-9999	-0.41	111	111
GNAQ	-0.056	0.14	-9999	-0.43	113	113
LPAR2	-0.001	0.013	-9999	-0.28	2	2
LPAR3	-0.11	0.27	-9999	-0.7	145	145
LPAR1	-0.014	0.1	-9999	-0.82	14	14
IL8	-0.19	0.23	-9999	-0.44	361	361
PTK2	-0.069	0.16	-9999	-0.48	121	121
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.063	0.16	-9999	-0.43	128	128
EGFR	-0.3	0.4	-9999	-0.82	331	331
PLCG1	-0.058	0.14	-9999	-0.44	112	112
PLD2	-0.069	0.16	-9999	-0.48	121	121
G12/G13	-0.01	0.065	-9999	-0.49	14	14
PI3K-beta	-0.011	0.066	-9999	-0.42	20	20
cell migration	-0.022	0.055	-9999	-0.24	7	7
SLC9A3R2	0	0.009	-9999	-10000	0	0
PXN	0.002	0.1	-9999	-0.42	15	15
HRAS/GTP	-0.032	0.11	-9999	-0.47	42	42
RAC1	0	0	-9999	-10000	0	0
MMP9	-0.13	0.14	-9999	-0.28	411	411
PRKCE	-0.001	0.027	-9999	-0.83	1	1
PRKCD	-0.002	0.13	-9999	-0.35	110	110
Gi(beta/gamma)	-0.032	0.12	-9999	-0.64	23	23
mol:LPA	-0.002	0.02	-9999	-0.22	8	8
TRIP6/p130 Cas/FAK1/Paxillin	-0.057	0.14	-9999	-0.54	16	16
MAPKKK cascade	0.013	0.12	-9999	-0.46	42	42
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	-0.44	117	117
GNA15	-0.056	0.14	-9999	-0.43	112	112
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
MAPT	-0.02	0.15	-9999	-0.44	96	96
GNA11	-0.056	0.14	-9999	-0.43	113	113
Rac1/GTP	0	0.034	-9999	-1	1	1
MMP2	0.01	0.11	-9999	-0.67	22	22

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	-0.001	0.027	-9999	-0.82	1	1
LAT2	-0.064	0.14	-9999	-0.43	75	75
AP1	-0.16	0.22	-9999	-0.46	297	297
mol:PIP3	-0.029	0.21	-9999	-0.43	182	182
IKBKB	0.001	0.12	-9999	-0.32	40	40
AKT1	-0.082	0.17	-9999	-0.67	33	33
IKBKG	0.001	0.12	-9999	-0.32	40	40
MS4A2	-0.068	0.23	-9999	-0.8	78	78
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-10000	0	0
MAP3K1	0.007	0.13	-9999	-0.45	30	30
mol:Ca2+	-0.014	0.16	-9999	-0.32	182	182
LYN	0.011	0.004	-9999	-10000	0	0
CBLB	-0.062	0.14	-9999	-0.43	75	75
SHC1	0	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.069	0.17	-9999	-0.51	124	124
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0	0	-9999	-10000	0	0
PLD2	-0.1	0.21	-9999	-0.5	182	182
PTPN13	-0.031	0.17	-9999	-0.55	50	50
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	31	31
SYK	0.01	0.01	-9999	-0.28	1	1
GRB2	0	0.009	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.088	0.18	-9999	-0.44	182	182
LAT	-0.064	0.14	-9999	-0.43	76	76
PAK2	-0.003	0.14	-9999	-0.5	31	31
NFATC2	-0.086	0.23	-9999	-0.87	61	61
HRAS	-0.013	0.15	-9999	-0.41	76	76
GAB2	-0.002	0.026	-9999	-10000	0	0
PLA2G1B	0.028	0.018	-9999	-10000	0	0
Fc epsilon R1	-0.12	0.26	-9999	-0.62	182	182
Antigen/IgE/Fc epsilon R1	-0.12	0.24	-9999	-0.58	182	182
mol:GDP	-0.019	0.15	-9999	-0.42	76	76
JUN	-0.008	0.081	-9999	-0.82	9	9
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
FOS	-0.26	0.38	-9999	-0.82	283	283
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.067	0.15	-9999	-0.45	77	77
CHUK	0.001	0.12	-9999	-0.32	40	40
KLRG1	-0.062	0.13	-9999	-0.4	77	77
VAV1	-0.064	0.14	-9999	-0.44	76	76
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.062	0.14	-9999	-0.43	75	75
negative regulation of mast cell degranulation	-0.057	0.12	-9999	-0.51	32	32
BTK	-0.061	0.14	-9999	-0.42	76	76
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.087	0.2	-9999	-0.44	183	183
GAB2/PI3K/SHP2	-0.091	0.19	-9999	-0.73	35	35
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.071	0.16	-9999	-0.38	143	143
RAF1	0.015	0.022	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.11	0.23	-9999	-0.53	183	183
FCER1G	0.002	0.016	-9999	-0.28	2	2
FCER1A	-0.12	0.3	-9999	-0.84	137	137
Antigen/IgE/Fc epsilon R1/Fyn	-0.11	0.23	-9999	-0.54	182	182
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	0.012	0.059	-9999	-0.56	4	4
DUSP1	-0.11	0.28	-9999	-0.82	124	124
NF-kappa-B/RelA	-0.027	0.055	-9999	-0.24	1	1
actin cytoskeleton reorganization	-0.028	0.15	-9999	-0.42	75	75
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.054	0.12	-9999	-0.51	33	33
FER	-0.065	0.14	-9999	-0.44	79	79
RELA	0	0	-9999	-10000	0	0
ITK	-0.033	0.11	-9999	-0.62	29	29
SOS1	0	0	-9999	-10000	0	0
PLCG1	-0.017	0.16	-9999	-0.43	76	76
cytokine secretion	-0.02	0.04	-9999	-10000	0	0
SPHK1	-0.065	0.14	-9999	-0.44	78	78
PTK2	-0.03	0.16	-9999	-0.44	75	75
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.091	0.19	-9999	-0.46	182	182
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.024	0.2	-9999	-0.48	85	85
MAP2K2	0.022	0.019	-9999	-10000	0	0
MAP2K1	0.022	0.019	-9999	-10000	0	0
MAP2K7	0	0	-9999	-10000	0	0
KLRG1/SHP2	-0.058	0.12	-9999	-0.52	32	32
MAP2K4	0.016	0.036	-9999	-1	1	1
Fc epsilon R1/FcgammaRIIB	-0.12	0.24	-9999	-0.57	183	183
mol:Choline	-0.099	0.21	-9999	-0.5	182	182
SHC/Grb2/SOS1	-0.056	0.13	-9999	-0.54	30	30
FYN	-0.001	0.027	-9999	-0.82	1	1
DOK1	0	0.009	-9999	-10000	0	0
PXN	-0.02	0.15	-9999	-0.54	30	30
HCLS1	-0.062	0.14	-9999	-0.43	75	75
PRKCB	-0.016	0.16	-9999	-0.37	90	90
FCGR2B	-0.003	0.048	-9999	-0.69	4	4
IGHE	0	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.058	0.12	-9999	-0.52	32	32
LCP2	0	0.009	-9999	-0.28	1	1
PLA2G4A	-0.11	0.21	-9999	-0.52	157	157
RASA1	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.099	0.21	-9999	-0.5	182	182
IKK complex	0.019	0.094	-9999	-0.23	38	38
WIPF1	0	0	-9999	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.055	0.3	-10000	0	-0.83	109	109
IHH	-0.013	0.078	-10000	0	-0.5	3	3
SHH Np/Cholesterol/GAS1	-0.03	0.12	-10000	0	-0.52	49	49
LRPAP1	0	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.03	0.12	0.52	49	-10000	0	49
SMO/beta Arrestin2	-0.077	0.24	-10000	0	-0.86	68	68
SMO	-0.054	0.26	-10000	0	-0.92	68	68
AKT1	-0.004	0.096	-10000	0	-0.31	66	66
ARRB2	0	0	-10000	0	-10000	0	0
BOC	-0.061	0.22	-10000	0	-0.82	68	68
ADRBK1	0	0	-10000	0	-10000	0	0
heart looping	-0.035	0.26	-10000	0	-0.9	68	68
STIL	-0.04	0.22	-10000	0	-0.73	70	70
DHH N/PTCH2	-0.071	0.21	-10000	0	-0.67	97	97
DHH N/PTCH1	-0.091	0.25	-10000	0	-0.76	97	97
PIK3CA	0	0.009	-10000	0	-10000	0	0
DHH	-0.024	0.14	-10000	0	-0.82	26	26
PTHLH	-0.083	0.39	-10000	0	-1.1	109	109
determination of left/right symmetry	-0.035	0.26	-10000	0	-0.9	68	68
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
skeletal system development	-0.08	0.38	-10000	0	-1.1	109	109
IHH N/Hhip	-0.01	0.047	-10000	0	-0.68	1	1
DHH N/Hhip	-0.021	0.11	-10000	0	-0.65	27	27
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.035	0.26	-10000	0	-0.9	68	68
pancreas development	-0.004	0.039	-10000	0	-0.82	1	1
HHAT	-0.001	0.027	-10000	0	-0.82	1	1
PI3K	-0.001	0.022	-10000	0	-0.63	1	1
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.043	0.18	-10000	0	-0.82	48	48
somite specification	-0.035	0.26	-10000	0	-0.9	68	68
SHH Np/Cholesterol/PTCH1	-0.072	0.21	-10000	0	-0.78	67	67
SHH Np/Cholesterol/PTCH2	-0.046	0.14	-10000	0	-0.52	78	78
SHH Np/Cholesterol/Megalin	-0.14	0.22	-10000	0	-0.51	238	238
SHH	0.01	0.036	-10000	0	-0.64	1	1
catabolic process	-0.048	0.26	-10000	0	-0.88	74	74
SMO/Vitamin D3	-0.075	0.23	-10000	0	-0.84	68	68
SHH Np/Cholesterol/Hhip	-0.005	0.035	-10000	0	-0.52	2	2
LRP2	-0.22	0.36	-10000	0	-0.78	260	260
receptor-mediated endocytosis	-0.15	0.26	-10000	0	-0.84	85	85
SHH Np/Cholesterol/BOC	-0.041	0.14	-10000	0	-0.52	69	69
SHH Np/Cholesterol/CDO	-0.01	0.063	-10000	0	-0.51	13	13
mesenchymal cell differentiation	0.005	0.035	0.51	2	-10000	0	2
mol:Vitamin D3	-0.031	0.23	-10000	0	-0.79	67	67
IHH N/PTCH2	-0.065	0.2	-10000	0	-0.7	77	77
CDON	-0.011	0.094	-10000	0	-0.82	12	12
IHH N/PTCH1	-0.046	0.27	-10000	0	-0.89	74	74
Megalin/LRPAP1	-0.17	0.28	-10000	0	-0.63	237	237
PTCH2	-0.07	0.23	-10000	0	-0.82	77	77
SHH Np/Cholesterol	-0.003	0.025	-10000	0	-0.52	1	1
PTCH1	-0.049	0.26	-10000	0	-0.89	74	74
HHIP	-0.004	0.039	-10000	0	-0.82	1	1

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.058	0.2	-9999	-0.84	56	56
PDGF/PDGFRA/CRKL	-0.039	0.15	-9999	-0.64	55	55
positive regulation of JUN kinase activity	-0.03	0.12	-9999	-0.49	55	55
CRKL	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.042	0.15	-9999	-0.64	55	55
AP1	-0.38	0.55	-9999	-1.2	283	283
mol:IP3	-0.034	0.16	-9999	-0.66	55	55
PLCG1	-0.034	0.16	-9999	-0.66	55	55
PDGF/PDGFRA/alphaV Integrin	-0.039	0.15	-9999	-0.64	55	55
RAPGEF1	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
mol:Ca2+	-0.034	0.16	-9999	-0.66	55	55
CAV3	-0.001	0.016	-9999	-0.28	3	3
CAV1	-0.17	0.34	-9999	-0.82	191	191
SHC/Grb2/SOS1	-0.03	0.12	-9999	-0.49	55	55
PDGF/PDGFRA/Shf	-0.039	0.16	-9999	-0.65	55	55
FOS	-0.34	0.56	-9999	-1.2	283	283
JUN	-0.027	0.074	-9999	-0.71	9	9
oligodendrocyte development	-0.038	0.15	-9999	-0.64	55	55
GRB2	0	0.009	-9999	-10000	0	0
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
mol:DAG	-0.034	0.16	-9999	-0.66	55	55
PDGF/PDGFRA	-0.058	0.2	-9999	-0.84	56	56
actin cytoskeleton reorganization	-0.039	0.15	-9999	-0.64	56	56
SRF	0.016	0.022	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
PI3K	-0.034	0.13	-9999	-0.55	56	56
PDGF/PDGFRA/Crk/C3G	-0.033	0.13	-9999	-0.55	55	55
JAK1	-0.023	0.16	-9999	-0.64	55	55
ELK1/SRF	-0.026	0.12	-9999	-0.5	55	55
SHB	-0.001	0.029	-9999	-0.55	2	2
SHF	-0.001	0.029	-9999	-0.55	2	2
CSNK2A1	0.019	0.027	-9999	-10000	0	0
GO:0007205	-0.036	0.17	-9999	-0.68	55	55
SOS1	0	0	-9999	-10000	0	0
Ras protein signal transduction	-0.03	0.12	-9999	-0.49	55	55
PDGF/PDGFRA/SHB	-0.04	0.15	-9999	-0.64	56	56
PDGF/PDGFRA/Caveolin-1	-0.17	0.32	-9999	-0.74	210	210
ITGAV	0	0	-9999	-10000	0	0
ELK1	-0.035	0.16	-9999	-0.61	55	55
PIK3CA	0	0.009	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.039	0.15	-9999	-0.64	55	55
JAK-STAT cascade	-0.023	0.16	-9999	-0.63	55	55
cell proliferation	-0.039	0.15	-9999	-0.64	55	55

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	-0.003	0.035	-9999	-0.64	2	2
PDGFRB	-0.002	0.039	-9999	-0.83	2	2
SPHK1	-0.025	0.059	-9999	-1.1	2	2
mol:S1P	-0.031	0.061	-9999	-0.98	2	2
S1P1/S1P/Gi	-0.1	0.23	-9999	-0.57	86	86
GNAO1	-0.027	0.15	-9999	-0.58	46	46
PDGFB-D/PDGFRB/PLCgamma1	-0.12	0.18	-9999	-0.61	57	57
PLCG1	-0.09	0.22	-9999	-0.57	76	76
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.002	0.039	-9999	-0.83	2	2
GNAI2	0.007	0.006	-9999	-10000	0	0
GNAI3	0	0.001	-9999	-10000	0	0
GNAI1	-0.043	0.18	-9999	-0.84	47	47
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.007	0.034	-9999	-0.57	2	2
S1P1/S1P	-0.044	0.072	-9999	-0.68	4	4
negative regulation of cAMP metabolic process	-0.098	0.22	-9999	-0.38	318	318
MAPK3	-0.16	0.31	-9999	-0.58	308	308
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	0.039	-9999	-0.83	2	2
PLCB2	-0.008	0.084	-9999	-0.57	5	5
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.037	0.059	-9999	-0.55	4	4
receptor internalization	-0.042	0.067	-9999	-0.62	4	4
PTGS2	-0.33	0.56	-9999	-1.1	308	308
Rac1/GTP	-0.037	0.059	-9999	-0.55	4	4
RHOA	0	0	-9999	-10000	0	0
VEGFA	-0.003	0.028	-9999	-0.28	9	9
negative regulation of T cell proliferation	-0.098	0.22	-9999	-0.38	318	318
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.007	0.078	-9999	-0.83	8	8
MAPK1	-0.16	0.31	-9999	-0.58	308	308
S1P1/S1P/PDGFB-D/PDGFRB	-0.052	0.084	-9999	-0.71	5	5
ABCC1	0	0	-9999	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.081	0.19	0.66	76	-10000	0	76
KIRREL	-0.069	0.23	-10000	0	-0.83	76	76
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.081	0.19	-10000	0	-0.66	76	76
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	-0.058	0.14	-10000	0	-0.51	76	76
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.034	0.1	-10000	0	-0.37	76	76
FYN	-0.054	0.14	-10000	0	-0.49	76	76
mol:Ca2+	-0.058	0.14	-10000	0	-0.5	76	76
mol:DAG	-0.058	0.14	-10000	0	-0.51	76	76
NPHS2	-0.008	0.029	-10000	0	-0.28	5	5
mol:IP3	-0.058	0.14	-10000	0	-0.51	76	76
regulation of endocytosis	-0.026	0.13	-10000	0	-0.45	76	76
Nephrin/NEPH1/podocin/Cholesterol	-0.061	0.14	-10000	0	-0.52	76	76
establishment of cell polarity	-0.081	0.19	-10000	0	-0.66	76	76
Nephrin/NEPH1/podocin/NCK1-2	-0.026	0.14	-10000	0	-0.46	76	76
Nephrin/NEPH1/beta Arrestin2	-0.026	0.14	-10000	0	-0.46	76	76
NPHS1	-0.05	0.1	-10000	0	-0.28	150	150
Nephrin/NEPH1/podocin	-0.049	0.14	-10000	0	-0.49	76	76
TJP1	-0.001	0.027	-10000	0	-0.82	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	-0.058	0.14	-10000	0	-0.51	76	76
CD2AP	0	0.009	-10000	0	-0.28	1	1
Nephrin/NEPH1/podocin/GRB2	-0.058	0.14	-10000	0	-0.51	76	76
GRB2	0	0.009	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.061	0.15	-10000	0	-0.51	83	83
cytoskeleton organization	-0.044	0.13	-10000	0	-0.47	76	76
Nephrin/NEPH1	-0.058	0.14	-10000	0	-0.5	76	76
Nephrin/NEPH1/ZO-1	-0.064	0.16	-10000	0	-0.55	76	76

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.005	0.031	-10000	0	-0.44	1	1
adherens junction organization	0.031	0.066	-10000	0	-0.31	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.14	0.19	-10000	0	-0.39	327	327
FMN1	0.024	0.09	-10000	0	-0.48	16	16
mol:IP3	-0.006	0.032	-10000	0	-0.41	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.01	0.057	-10000	0	-0.32	29	29
CTNNB1	0.001	0.004	-10000	0	-10000	0	0
AKT1	-0.007	0.036	-10000	0	-0.4	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.016	0.089	-10000	0	-0.52	28	28
CTNND1	0	0.009	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.032	0.06	-10000	0	-0.3	29	29
VASP	0.032	0.061	-10000	0	-10000	0	0
ZYX	0.032	0.061	-10000	0	-10000	0	0
JUB	0.03	0.068	-10000	0	-0.44	4	4
EGFR(dimer)	-0.17	0.22	-10000	0	-0.45	327	327
E-cadherin/beta catenin-gamma catenin	-0.017	0.093	-10000	0	-0.53	29	29
mol:PI-3-4-5-P3	-0.007	0.04	-10000	0	-0.43	1	1
PIK3CA	0	0.009	-10000	0	-10000	0	0
PI3K	-0.007	0.04	-10000	0	-0.44	1	1
FYN	0.043	0.038	-10000	0	-0.37	2	2
mol:Ca2+	-0.006	0.032	-10000	0	-0.4	1	1
JUP	-0.001	0.03	-10000	0	-0.82	1	1
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
mol:DAG	-0.006	0.032	-10000	0	-0.41	1	1
CDH1	-0.025	0.14	-10000	0	-0.82	28	28
RhoA/GDP	-0.14	0.19	-10000	0	-0.39	327	327
establishment of polarity of embryonic epithelium	0.032	0.06	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
EGFR	-0.3	0.4	-10000	0	-0.82	331	331
CASR	-0.006	0.03	-10000	0	-0.38	1	1
RhoA/GTP	-0.005	0.028	-10000	0	-0.37	1	1
AKT2	-0.007	0.036	-10000	0	-0.4	1	1
actin cable formation	0.031	0.088	-10000	0	-0.46	16	16
apoptosis	0.006	0.036	0.42	1	-10000	0	1
CTNNA1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.15	0.2	-10000	0	-0.42	327	327
PIP5K1A	0.032	0.061	-10000	0	-0.3	29	29
PLCG1	-0.006	0.033	-10000	0	-0.42	1	1
Rac1/GTP	-0.15	0.2	-10000	0	-0.41	327	327
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.007	0.058	-9999	-0.48	13	13
RGS9BP	-0.016	0.064	-9999	-0.28	51	51
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.003	0.029	-9999	-0.28	10	10
mol:Na +	-0.02	0.05	-9999	-10000	0	0
mol:ADP	0.006	0.03	-9999	-10000	0	0
GNAT2	-0.001	0.016	-9999	-0.28	3	3
RGS9-1/Gbeta5/R9AP	-0.067	0.17	-9999	-0.56	97	97
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.013	-9999	-10000	0	0
GRK7	-0.003	0.03	-9999	-0.28	11	11
CNGB3	-0.01	0.052	-9999	-0.28	33	33
Cone Metarhodopsin II/X-Arrestin	-0.001	0.016	-9999	-10000	0	0
mol:Ca2+	-0.096	0.077	-9999	-10000	0	0
Cone PDE6	-0.058	0.15	-9999	-0.48	97	97
Cone Metarhodopsin II	-0.003	0.02	-9999	-10000	0	0
Na + (4 Units)	-0.096	0.076	-9999	-10000	0	0
GNAT2/GDP	-0.058	0.15	-9999	-0.48	97	97
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	0.005	0.013	-9999	-10000	0	0
Cone Transducin	-0.008	0.061	-9999	-0.51	13	13
SLC24A2	-0.18	0.14	-9999	-0.28	574	574
GNB3/GNGT2	-0.009	0.075	-9999	-0.63	13	13
GNB3	-0.011	0.095	-9999	-0.75	14	14
GNAT2/GTP	-0.001	0.011	-9999	-10000	0	0
CNGA3	-0.027	0.083	-9999	-0.28	90	90
ARR3	-0.002	0.024	-9999	-0.28	7	7
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.02	0.051	-9999	-10000	0	0
mol:Pi	-0.067	0.17	-9999	-0.56	97	97
Cone CNG Channel	-0.015	0.038	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.18	0.13	-9999	-0.28	574	574
RGS9	-0.091	0.26	-9999	-0.77	107	107
PDE6C	0	0	-9999	-10000	0	0
GNGT2	-0.001	0.027	-9999	-0.82	1	1
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.001	0.018	-9999	-0.28	4	4

×

TCGA08_rtk_signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.05	0.2	-10000	0	-0.82	56	56
HRAS	-0.001	0.013	-10000	0	-0.28	2	2
EGFR	-0.3	0.4	-10000	0	-0.82	331	331
AKT	0.016	0.074	-10000	0	-0.59	12	12
FOXO3	-0.002	0.039	-10000	0	-0.82	2	2
AKT1	0	0	-10000	0	-10000	0	0
FOXO1	-0.007	0.077	-10000	0	-0.82	8	8
AKT3	-0.011	0.094	-10000	0	-0.82	12	12
FOXO4	0	0	-10000	0	-10000	0	0
MET	-0.14	0.31	-10000	0	-0.82	155	155
PIK3CA	0	0.009	-10000	0	-10000	0	0
PIK3CB	0	0	-10000	0	-10000	0	0
NRAS	-0.001	0.013	-10000	0	-0.28	2	2
PIK3CG	-0.009	0.083	-10000	0	-0.82	9	9
PIK3R3	0	0.009	-10000	0	-10000	0	0
PIK3R2	0	0	-10000	0	-10000	0	0
NF1	-0.001	0.027	-10000	0	-0.82	1	1
RAS	-0.093	0.16	0.26	1	-0.27	353	354
ERBB2	-0.024	0.078	-10000	0	-10000	0	0
proliferation/survival/translation	-0.006	0.054	0.28	5	-10000	0	5
PI3K	-0.082	0.16	-10000	0	-0.26	338	338
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
KRAS	0	0.009	-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	0.039	-10000	0	-0.82	2	2

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.054	0.11	-9999	-0.28	176	176
mol:Halofuginone	0	0.002	-9999	-10000	0	0
ITGA1	-0.002	0.039	-9999	-0.82	2	2
CDKN1A	-0.06	0.09	-9999	-0.87	1	1
PRL-3/alpha Tubulin	-0.002	0.018	-9999	-10000	0	0
mol:Ca2+	-0.035	0.1	-9999	-0.65	14	14
AGT	-0.05	0.14	-9999	-0.82	14	14
CCNA2	-0.17	0.25	-9999	-0.52	295	295
TUBA1B	0	0	-9999	-10000	0	0
EGR1	-0.19	0.3	-9999	-0.63	295	295
CDK2/Cyclin E1	-0.068	0.089	-9999	-0.78	1	1
MAPK3	0.02	0.021	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0.008	-9999	-10000	0	0
MAPK1	0.02	0.021	-9999	-10000	0	0
PTP4A1	-0.13	0.25	-9999	-0.49	295	295
PTP4A3	-0.003	0.029	-9999	-10000	0	0
PTP4A2	-0.001	0.013	-9999	-0.28	2	2
ITGB1	0.02	0.021	-9999	-10000	0	0
SRC	0	0.009	-9999	-10000	0	0
RAC1	-0.059	0.086	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.15	0.21	-9999	-0.62	3	3
RABGGTA	0	0	-9999	-10000	0	0
BCAR1	0.001	0.009	-9999	-10000	0	0
RHOC	-0.059	0.086	-9999	-10000	0	0
RHOA	-0.059	0.086	-9999	-10000	0	0
cell motility	-0.039	0.11	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.15	0.21	-9999	-0.45	295	295
PRL-3/alpha1 Integrin	-0.003	0.035	-9999	-0.63	2	2
ROCK1	-0.039	0.11	-9999	-10000	0	0
RABGGTB	0	0	-9999	-10000	0	0
CDK2	0	0	-9999	-10000	0	0
mitosis	-0.13	0.24	-9999	-0.48	295	295
ATF5	-0.001	0.018	-9999	-10000	0	0

×

Presenilin action in Notch and Wnt 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
Delta 1/NOTCH/NOTCH(cleaved)	-0.003	0.039	-10000	0	-0.52	5	5
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	-0.82	85	85
LRP6/FZD1	0	0.008	-10000	0	-10000	0	0
TLE1	-0.007	0.077	-10000	0	-0.83	8	8
AP1	-0.12	0.18	-10000	0	-0.38	287	287
NCSTN	0	0	-10000	0	-10000	0	0
ADAM10	-0.001	0.027	-10000	0	-0.82	1	1
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.008	0.045	-10000	0	-0.34	1	1
NICD/RBPSUH	-0.001	0.024	-10000	0	-0.72	1	1
WIF1	-0.44	0.41	-10000	0	-0.81	495	495
NOTCH1	-0.001	0.026	-10000	0	-0.77	1	1
PSENEN	0	0.009	-10000	0	-0.28	1	1
KREMEN2	-0.13	0.14	-10000	0	-0.28	431	431
DKK1	-0.079	0.2	-10000	0	-0.42	172	172
beta catenin/beta TrCP1	-0.011	0.023	-10000	0	-10000	0	0
APH1B	-0.001	0.027	-10000	0	-0.82	1	1
APH1A	0	0	-10000	0	-10000	0	0
AXIN1	0.003	0.011	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.003	0.042	-10000	0	-0.34	8	8
PSEN1	0	0	-10000	0	-10000	0	0
FOS	-0.26	0.38	-10000	0	-0.82	283	283
JUN	-0.008	0.081	-10000	0	-0.82	9	9
MAP3K7	0.001	0.01	-10000	0	-10000	0	0
CTNNB1	-0.004	0.036	0.24	2	-10000	0	2
MAPK3	0	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.075	0.11	-10000	0	-0.64	19	19
HNF1A	-0.001	0.023	-10000	0	-0.28	6	6
CTBP1	0.001	0.003	-10000	0	-10000	0	0
MYC	-0.033	0.22	-10000	0	-1.5	20	20
NKD1	-0.01	0.076	-10000	0	-0.43	22	22
FZD1	0	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.044	0.14	-10000	0	-0.46	86	86
apoptosis	-0.12	0.18	-10000	0	-0.38	287	287
Delta 1/NOTCHprecursor	-0.003	0.039	-10000	0	-0.51	5	5
DLL1	-0.004	0.054	-10000	0	-0.82	4	4
PPARD	-0.001	0.012	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.016	-10000	0	-0.46	1	1
APC	0.003	0.011	-10000	0	-0.22	1	1
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	0.14	-10000	0	-0.59	47	47
LRP6	-0.001	0.013	-10000	0	-0.28	2	2
CSNK1A1	0	0	-10000	0	-10000	0	0
NLK	0.002	0.01	-10000	0	-10000	0	0
CCND1	-0.011	0.09	-10000	0	-1.5	3	3
WNT1	0	0.009	-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	-0.82	19	19
NOTCH1 precursor/DVL1	-0.02	0.028	-10000	0	-0.64	1	1
GSK3B	0	0.002	-10000	0	-10000	0	0
FRAT1	0	0.003	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.044	0.14	-10000	0	-0.46	86	86
PPP2R5D	-0.016	0.04	0.36	6	-10000	0	6
MAPK1	0	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.27	0.25	-10000	0	-0.5	483	483
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.013	0.003	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.12	0.18	-9999	-0.39	285	285
MAP3K8	-0.005	0.062	-9999	-0.83	5	5
FOS	-0.037	0.13	-9999	-0.46	28	28
PRKCA	-0.02	0.13	-9999	-0.79	23	23
PTPN7	-0.008	0.069	-9999	-0.32	16	16
HRAS	-0.001	0.013	-9999	-0.28	2	2
PRKCB	-0.02	0.12	-9999	-0.7	21	21
NRAS	-0.001	0.013	-9999	-0.28	2	2
RAS family/GTP	-0.001	0.009	-9999	-10000	0	0
MAPK3	-0.008	0.072	-9999	-10000	0	0
MAP2K1	-0.013	0.14	-9999	-0.59	39	39
ELK1	-0.003	0.005	-9999	-10000	0	0
BRAF	-0.031	0.12	-9999	-0.6	35	35
mol:GTP	-0.002	0.003	-9999	-0.006	283	283
MAPK1	-0.008	0.072	-9999	-0.26	24	24
RAF1	-0.031	0.12	-9999	-0.6	35	35
KRAS	0	0.009	-9999	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.011	0.059	-10000	0	-0.34	29	29
epithelial cell differentiation	-0.014	0.081	-10000	0	-0.47	28	28
CYFIP2	-0.01	0.061	-10000	0	-0.32	29	29
ENAH	0.055	0.064	-10000	0	-10000	0	0
EGFR	-0.3	0.4	-10000	0	-0.82	331	331
EPHA2	-0.005	0.067	-10000	0	-0.82	6	6
MYO6	-0.014	0.078	-10000	0	-0.44	29	29
CTNNB1	0	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.005	0.034	-10000	0	-0.55	2	2
AQP5	-0.25	0.3	-10000	0	-0.61	372	372
CTNND1	0	0.009	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.013	0.075	-10000	0	-0.44	28	28
regulation of calcium-dependent cell-cell adhesion	-0.036	0.12	-10000	0	-0.45	73	73
EGF	-0.16	0.33	-10000	0	-0.82	183	183
NCKAP1	0	0	-10000	0	-10000	0	0
AQP3	-0.041	0.15	-10000	0	-0.6	49	49
cortical microtubule organization	-0.014	0.081	-10000	0	-0.47	28	28
GO:0000145	0.024	0.078	-10000	0	-0.42	28	28
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.015	0.082	-10000	0	-0.47	28	28
MLLT4	-0.005	0.061	-10000	0	-0.82	5	5
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	0.041	-10000	0	-0.5	6	6
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.035	0.08	-10000	0	-0.41	28	28
PVRL2	-0.001	0.016	-10000	0	-10000	0	0
ZYX	-0.014	0.076	-10000	0	-0.44	28	28
ARF6/GTP	-0.004	0.038	-10000	0	-0.46	6	6
CDH1	-0.025	0.14	-10000	0	-0.82	28	28
EGFR/EGFR/EGF/EGF	-0.25	0.27	-10000	0	-0.49	467	467
RhoA/GDP	-0.014	0.076	-10000	0	-0.44	28	28
actin cytoskeleton organization	0.03	0.081	-10000	0	-0.42	29	29
IGF-1R heterotetramer	-0.022	0.12	-10000	0	-0.61	33	33
GIT1	-0.001	0.018	-10000	0	-0.28	4	4
IGF1R	-0.022	0.12	-10000	0	-0.61	33	33
IGF1	-0.18	0.34	-10000	0	-0.82	197	197
DIAPH1	-0.001	0.033	-10000	0	-0.68	2	2
Wnt receptor signaling pathway	0.014	0.081	0.47	28	-10000	0	28
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	-0.014	0.075	-10000	0	-0.43	29	29
EFNA1	0	0.009	-10000	0	-10000	0	0
LPP	0.03	0.084	-10000	0	-0.42	31	31
Ephrin A1/EPHA2	-0.016	0.08	-10000	0	-0.42	34	34
SEC6/SEC8	-0.014	0.075	-10000	0	-0.79	1	1
MGAT3	-0.037	0.12	-10000	0	-0.46	73	73
HGF/MET	-0.11	0.22	-10000	0	-0.48	213	213
HGF	-0.051	0.2	-10000	0	-0.82	57	57
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.011	0.059	-10000	0	-0.34	29	29
actin cable formation	0.07	0.061	-10000	0	-10000	0	0
KIAA1543	0.03	0.092	-10000	0	-0.46	28	28
KIFC3	-0.015	0.079	-10000	0	-0.44	30	30
NCK1	0	0	-10000	0	-10000	0	0
EXOC3	0	0	-10000	0	-10000	0	0
ACTN1	-0.014	0.078	-10000	0	-0.44	29	29
NCK1/GIT1	-0.001	0.012	-10000	0	-10000	0	0
mol:GDP	-0.014	0.081	-10000	0	-0.47	28	28
EXOC4	0	0	-10000	0	-10000	0	0
STX4	-0.014	0.076	-10000	0	-0.44	28	28
PIP5K1C	-0.014	0.076	-10000	0	-0.44	28	28
LIMA1	-0.001	0.027	-10000	0	-0.82	1	1
ABI1	0	0	-10000	0	-10000	0	0
ROCK1	-0.012	0.06	-10000	0	-10000	0	0
adherens junction assembly	0.045	0.088	-10000	0	-0.66	4	4
IGF-1R heterotetramer/IGF1	-0.12	0.2	-10000	0	-0.46	231	231
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.004	0.048	-10000	0	-0.63	5	5
MET	-0.14	0.31	-10000	0	-0.82	155	155
PLEKHA7	-0.015	0.085	-10000	0	-0.48	28	28
mol:GTP	-0.004	0.041	-10000	0	-0.5	6	6
establishment of epithelial cell apical/basal polarity	-0.013	0.071	-10000	0	-0.74	1	1
cortical actin cytoskeleton stabilization	-0.011	0.059	-10000	0	-0.34	29	29
regulation of cell-cell adhesion	0.03	0.081	-10000	0	-0.42	29	29
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.011	0.059	-10000	0	-0.34	29	29

×

Signaling events mediated by HDAC Class III

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
EP300	0	0	-10000	0	-10000	0	0
HDAC4	-0.001	0.027	-10000	0	-0.82	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.029	0.069	0.63	1	-10000	0	1
CDKN1A	-0.001	0.032	-10000	0	-0.97	1	1
KAT2B	0	0	-10000	0	-10000	0	0
BAX	-0.001	0.016	-10000	0	-10000	0	0
FOXO3	-0.001	0.016	-10000	0	-0.34	2	2
FOXO1	-0.007	0.077	-10000	0	-0.82	8	8
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	-0.59	0.37	-10000	0	-0.8	670	670
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.01	0.021	-10000	0	-10000	0	0
PPARGC1A	-0.18	0.34	-10000	0	-0.82	195	195
FHL2	-0.005	0.062	-10000	0	-0.82	5	5
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.005	-10000	0	-10000	0	0
HIST2H4A	-0.029	0.069	-10000	0	-0.64	1	1
SIRT1/FOXO3a	0	0.013	-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	0.019	-10000	0	-0.55	1	1
SIRT1/Histone H1b	-0.002	0.009	-10000	0	-10000	0	0
apoptosis	0	0.009	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.12	0.23	-10000	0	-0.56	195	195
p53/SIRT1	0.001	0.015	0.43	1	-10000	0	1
SIRT1/FOXO4	0	0.006	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.007	0.061	-10000	0	-0.51	13	13
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	0.016	-10000	0	-10000	0	0
TP53	0	0.007	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.009	-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	-0.45	0.28	-10000	0	-0.64	644	644
ACSS2	-0.001	0.022	-10000	0	-0.64	1	1
SIRT1/PCAF/MYOD	-0.001	0.016	-10000	0	-10000	0	0

×

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	211	211
MAPK9	0	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.001	0.02	-10000	0	-10000	0	0
GNB1/GNG2	-0.004	0.049	-10000	0	-0.56	7	7
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	-0.52	210	210
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	210	-10000	0	210
GNAL	-0.19	0.35	-10000	0	-0.82	210	210
GNG2	-0.006	0.072	-10000	0	-0.82	7	7
CRH	-0.003	0.029	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	-0.002	0.026	-10000	0	-0.46	3	3
MAPK11	-0.001	0.021	-10000	0	-0.46	2	2

×

FAS signaling pathway (CD95)

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.01	0.052	0.29	30	-10000	0	30
RFC1	0.01	0.052	0.29	30	-10000	0	30
PRKDC	0.009	0.053	0.29	30	-10000	0	30
RIPK1	0	0	-10000	0	-10000	0	0
CASP7	-0.023	0.036	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.015	0.06	0.23	23	-0.4	8	31
MAP2K4	-0.058	0.16	-10000	0	-0.53	12	12
mol:ceramide	-0.029	0.11	-10000	0	-0.58	11	11
GSN	0.002	0.081	0.29	29	-0.52	13	42
FASLG/FAS/FADD/FAF1/Caspase 8	-0.028	0.062	0.23	10	-0.47	8	18
FAS	-0.003	0.048	-10000	0	-0.84	3	3
BID	0.001	0.005	-10000	0	-10000	0	0
MAP3K1	-0.021	0.092	-10000	0	-0.3	6	6
MAP3K7	0	0.009	-10000	0	-10000	0	0
RB1	0.009	0.055	0.29	29	-0.43	2	31
CFLAR	0	0	-10000	0	-10000	0	0
HGF/MET	-0.14	0.27	-10000	0	-0.62	204	204
ARHGDIB	0.01	0.052	0.29	30	-10000	0	30
FADD	-0.005	0.039	-10000	0	-0.3	16	16
actin filament polymerization	-0.002	0.081	0.52	13	-0.29	29	42
NFKB1	-0.077	0.1	-10000	0	-0.29	11	11
MAPK8	-0.12	0.24	-10000	0	-0.43	340	340
DFFA	0.01	0.052	0.29	30	-10000	0	30
DNA fragmentation during apoptosis	0.01	0.052	0.29	30	-10000	0	30
FAS/FADD/MET	-0.099	0.22	-10000	0	-0.58	154	154
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.001	0.046	-10000	0	-0.28	24	24
FAF1	0.007	0.006	-10000	0	-10000	0	0
PARP1	0.01	0.052	0.29	30	-10000	0	30
DFFB	0.01	0.052	0.29	30	-10000	0	30
CHUK	-0.066	0.088	-10000	0	-0.3	1	1
FASLG	-0.01	0.088	-10000	0	-0.36	41	41
FAS/FADD	-0.006	0.047	-10000	0	-0.7	3	3
HGF	-0.051	0.2	-10000	0	-0.82	57	57
LMNA	0.009	0.047	0.26	30	-10000	0	30
CASP6	0.01	0.052	0.29	30	-10000	0	30
CASP10	-0.003	0.048	-10000	0	-0.84	3	3
CASP3	0.012	0.063	0.35	30	-10000	0	30
PTPN13	-0.022	0.13	-10000	0	-0.82	24	24
CASP8	0.002	0.013	-10000	0	-10000	0	0
IL6	-0.48	0.68	-10000	0	-1.4	338	338
MET	-0.14	0.31	-10000	0	-0.82	155	155
ICAD/CAD	0.01	0.048	0.27	30	-10000	0	30
FASLG/FAS/FADD/FAF1/Caspase 10	-0.056	0.093	-10000	0	-0.59	11	11
activation of caspase activity by cytochrome c	0.001	0.005	-10000	0	-10000	0	0
PAK2	0.01	0.051	0.29	30	-10000	0	30
BCL2	-0.023	0.15	-10000	0	-0.82	30	30

×

LPA4-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.002	0.11	-9999	-0.56	35	35
ADCY5	-0.16	0.27	-9999	-0.56	289	289
ADCY6	0.019	0.019	-9999	-0.56	1	1
ADCY7	0.019	0.019	-9999	-0.56	1	1
ADCY1	-0.006	0.094	-9999	-0.56	20	20
ADCY2	-0.031	0.16	-9999	-0.56	71	71
ADCY3	0.019	0.02	-9999	-0.56	1	1
ADCY8	0.009	0.033	-9999	-0.56	1	1
PRKCE	0.01	0.022	-9999	-0.64	1	1
ADCY9	0.019	0.019	-9999	-0.56	1	1
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.032	0.1	-9999	-0.31	71	71

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.57	0.38	-9999	-0.82	637	637
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	-0.003	0.028	-9999	-10000	0	0
TCEB1	-0.001	0.016	-9999	-10000	0	0
HIF1A/p53	-0.001	0.004	-9999	-10000	0	0
HIF1A	-0.002	0.006	-9999	-10000	0	0
COPS5	0	0.009	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.001	0.011	-9999	-10000	0	0
FIH (dimer)	0	0	-9999	-10000	0	0
CDKN2A	-0.045	0.1	-9999	-10000	0	0
ARNT/IPAS	-0.44	0.29	-9999	-0.63	637	637
HIF1AN	0	0	-9999	-10000	0	0
GNB2L1	0	0	-9999	-10000	0	0
HIF1A/ARNT	-0.001	0.004	-9999	-10000	0	0
CUL2	0	0	-9999	-10000	0	0
OS9	0	0.009	-9999	-0.28	1	1
RACK1/Elongin B/Elongin C	-0.002	0.015	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.001	0.005	-9999	-10000	0	0
PHD1-3/OS9	-0.01	0.035	-9999	-0.5	1	1
HIF1A/RACK1/Elongin B/Elongin C	0	0.01	-9999	-10000	0	0
VHL	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-10000	0	0
HIF1A/JAB1	-0.001	0.006	-9999	-10000	0	0
EGLN3	-0.022	0.075	-9999	-0.28	72	72
EGLN2	-0.001	0.018	-9999	-10000	0	0
EGLN1	-0.001	0.027	-9999	-0.82	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	-0.017	0.037	-9999	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.002	0.039	-9999	-0.82	2	2
alphaV beta3 Integrin	-0.014	0.091	-9999	-0.63	19	19
PTK2	-0.055	0.17	-9999	-0.56	86	86
positive regulation of JNK cascade	-0.032	0.099	-9999	-0.34	86	86
CDC42/GDP	0.006	0.15	-9999	-0.46	86	86
Rac1/GDP	0.008	0.15	-9999	-0.46	86	86
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.04	0.12	-9999	-0.42	86	86
nectin-3/I-afadin	-0.062	0.2	-9999	-0.66	86	86
RAPGEF1	0	0.17	-9999	-0.52	86	86
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.013	0.2	-9999	-0.61	86	86
PDGFB-D/PDGFRB	-0.002	0.038	-9999	-0.82	2	2
TLN1	-0.026	0.09	-9999	-0.55	10	10
Rap1/GTP	-0.034	0.11	-9999	-0.36	86	86
IQGAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.003	0.037	-9999	-0.51	5	5
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.062	0.2	-9999	-0.66	86	86
PVR	0	0	-9999	-10000	0	0
Necl-5(dimer)	0	0	-9999	-10000	0	0
mol:GDP	-0.003	0.19	-9999	-0.58	86	86
MLLT4	-0.005	0.061	-9999	-0.82	5	5
PIK3CA	0	0.009	-9999	-10000	0	0
PI3K	-0.047	0.15	-9999	-0.49	89	89
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.003	0.047	-9999	-0.63	5	5
positive regulation of lamellipodium assembly	-0.034	0.1	-9999	-0.36	86	86
PVRL1	0	0	-9999	-10000	0	0
PVRL3	-0.077	0.24	-9999	-0.82	85	85
PVRL2	-0.001	0.016	-9999	-10000	0	0
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
CDH1	-0.025	0.14	-9999	-0.82	28	28
CLDN1	-0.038	0.16	-9999	-0.82	34	34
JAM-A/CLDN1	-0.07	0.19	-9999	-0.55	112	112
SRC	-0.066	0.21	-9999	-0.7	86	86
ITGB3	-0.018	0.12	-9999	-0.82	19	19
nectin-1(dimer)/I-afadin/I-afadin	-0.003	0.047	-9999	-0.63	5	5
FARP2	-0.008	0.18	-9999	-0.57	86	86
RAC1	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.054	0.17	-9999	-0.57	86	86
nectin-1/I-afadin	-0.003	0.047	-9999	-0.63	5	5
nectin-2/I-afadin	-0.004	0.048	-9999	-0.63	5	5
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	-0.054	0.17	-9999	-0.57	86	86
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.032	0.099	-9999	-0.34	86	86
alphaV/beta3 Integrin/Talin	-0.032	0.11	-9999	-0.62	23	23
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.004	0.048	-9999	-0.63	5	5
nectin-2(dimer)/I-afadin/I-afadin	-0.004	0.048	-9999	-0.63	5	5
PIP5K1C	-0.029	0.098	-9999	-0.59	10	10
VAV2	-0.01	0.18	-9999	-0.58	86	86
RAP1/GDP	-0.04	0.12	-9999	-0.42	86	86
ITGAV	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.054	0.17	-9999	-0.57	86	86
nectin-3(dimer)/I-afadin/I-afadin	-0.062	0.2	-9999	-0.66	86	86
Rac1/GTP	-0.042	0.13	-9999	-0.44	86	86
PTPRM	-0.032	0.11	-9999	-0.33	89	89
E-cadherin/beta catenin/alpha catenin	-0.016	0.085	-9999	-0.46	32	32
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.008	-10000	0	-10000	0	0
SMAD4	0	0	-10000	0	-10000	0	0
DKK2	-0.018	0.12	-10000	0	-0.82	19	19
TLE1	-0.004	0.079	-10000	0	-0.83	8	8
MACF1	0	0	-10000	0	-10000	0	0
CTNNB1	0.11	0.088	-10000	0	-10000	0	0
WIF1	-0.44	0.41	-10000	0	-0.81	495	495
beta catenin/RanBP3	0.013	0.074	0.37	35	-10000	0	35
KREMEN2	-0.13	0.14	-10000	0	-0.28	431	431
DKK1	-0.079	0.2	-10000	0	-0.42	172	172
beta catenin/beta TrCP1	0.1	0.085	-10000	0	-10000	0	0
FZD1	0	0	-10000	0	-10000	0	0
AXIN2	-0.01	0.2	-10000	0	-1.6	14	14
AXIN1	0	0.002	-10000	0	-10000	0	0
RAN	0	0.002	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.004	0.019	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.095	0.074	-10000	0	-0.49	4	4
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	0.002	0.026	-10000	0	-0.28	3	3
CTBP1	0.004	0.015	-10000	0	-10000	0	0
MYC	-0.019	0.23	-10000	0	-1.6	20	20
RANBP3	0	0.002	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.075	0.11	-10000	0	-0.64	19	19
NKD1	-0.01	0.076	-10000	0	-0.43	22	22
TCF4	-0.002	0.068	-10000	0	-0.82	6	6
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	36	-0.44	1	37
LEF1	-0.034	0.098	-10000	0	-0.28	118	118
DVL1	0.073	0.065	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.1	0.084	-10000	0	-0.53	3	3
DKK1/LRP6/Kremen 2	-0.11	0.14	-10000	0	-0.59	47	47
LRP6	-0.001	0.013	-10000	0	-0.28	2	2
CSNK1A1	0.004	0.017	-10000	0	-10000	0	0
NLK	0	0.009	-10000	0	-10000	0	0
CCND1	0.003	0.1	-10000	0	-1.6	3	3
WNT1	0	0.009	-10000	0	-0.28	1	1
GSK3A	0.003	0.005	-10000	0	-10000	0	0
GSK3B	0	0	-10000	0	-10000	0	0
FRAT1	0	0	-10000	0	-10000	0	0
PPP2R5D	0.045	0.047	0.35	7	-10000	0	7
APC	0	0.005	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.15	0.14	0.27	483	-10000	0	483
CREBBP	0.004	0.015	-10000	0	-10000	0	0

×

Glypican 2 network

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
MDK	-0.01	0.052	-9999	-10000	0	0
GPC2	-0.034	0.099	-9999	-0.29	105	105
GPC2/Midkine	-0.028	0.077	-9999	-0.4	16	16
neuron projection morphogenesis	-0.028	0.077	-9999	-0.4	16	16

×

IL27-mediated signaling events

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
TGFB1	0.002	0.012	-10000	0	-0.28	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.023	0.11	0.45	21	-10000	0	21
IL27/IL27R/JAK1	-0.056	0.17	-10000	0	-0.68	27	27
TBX21	-0.032	0.21	-10000	0	-0.62	63	63
IL12B	-0.048	0.11	-10000	0	-0.28	176	176
IL12A	-0.029	0.15	-10000	0	-0.55	63	63
IL6ST	-0.067	0.24	-10000	0	-0.83	79	79
IL27RA/JAK1	-0.006	0.065	-10000	0	-1.3	2	2
IL27	-0.023	0.084	-10000	0	-0.29	30	30
TYK2	0.009	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.13	0.18	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.023	0.11	0.45	21	-10000	0	21
T cell proliferation during immune response	0.023	0.11	0.45	21	-10000	0	21
MAPKKK cascade	-0.023	0.11	-10000	0	-0.45	21	21
STAT3	0	0	-10000	0	-10000	0	0
STAT2	0	0	-10000	0	-10000	0	0
STAT1	-0.006	0.04	-10000	0	-0.28	19	19
IL12RB1	-0.011	0.06	-10000	0	-0.3	35	35
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.049	0.23	-10000	0	-0.64	79	79
IL27/IL27R/JAK2/TYK2	-0.023	0.12	-10000	0	-0.46	20	20
positive regulation of T cell mediated cytotoxicity	-0.023	0.11	-10000	0	-0.45	21	21
STAT1 (dimer)	-0.077	0.22	0.47	19	-0.76	39	58
JAK2	0.003	0.028	-10000	0	-0.83	1	1
JAK1	0	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	-0.035	0.099	-10000	0	-0.53	8	8
T cell proliferation	-0.19	0.25	-10000	0	-0.49	343	343
IL12/IL12R/TYK2/JAK2	0.013	0.07	-10000	0	-10000	0	0
IL17A	-0.13	0.18	-10000	0	-10000	0	0
mast cell activation	0.023	0.11	0.45	21	-10000	0	21
IFNG	0.001	0.022	-10000	0	-0.076	9	9
T cell differentiation	-0.003	0.005	-10000	0	-0.018	27	27
STAT3 (dimer)	-0.035	0.099	-10000	0	-0.5	10	10
STAT5A (dimer)	-0.038	0.11	-10000	0	-0.53	16	16
STAT4 (dimer)	-0.053	0.14	-10000	0	-0.53	46	46
STAT4	-0.033	0.16	-10000	0	-0.81	37	37
T cell activation	-0.008	0.008	0.13	2	-10000	0	2
IL27R/JAK2/TYK2	-0.046	0.15	-10000	0	-0.58	35	35
GATA3	-0.042	0.28	-10000	0	-1.5	33	33
IL18	0.006	0.03	-10000	0	-10000	0	0
positive regulation of mast cell cytokine production	-0.034	0.098	-10000	0	-0.49	10	10
IL27/EBI3	-0.023	0.081	-10000	0	-0.56	11	11
IL27RA	0	0.071	-10000	0	-1.4	2	2
IL6	-0.3	0.4	-10000	0	-0.82	338	338
STAT5A	-0.006	0.072	-10000	0	-0.82	7	7
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.003	0.027	0.48	2	-10000	0	2
IL1B	0.002	0.076	-10000	0	-0.53	16	16
EBI3	-0.005	0.078	-10000	0	-0.63	11	11
TNF	-0.003	0.085	-10000	0	-0.64	14	14

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.003	0.13	-10000	0	-0.37	74	74
TBX21	-0.009	0.34	-10000	0	-1.3	47	47
B2M	0.011	0.005	-10000	0	-10000	0	0
TYK2	0.017	0.015	-10000	0	-10000	0	0
IL12RB1	0.005	0.066	-10000	0	-0.3	35	35
GADD45B	0.037	0.21	-10000	0	-0.83	25	25
IL12RB2	-0.061	0.2	-10000	0	-0.51	118	118
GADD45G	0.031	0.21	-10000	0	-0.89	21	21
natural killer cell activation	0.007	0.017	-10000	0	-10000	0	0
RELB	-0.002	0.024	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
IL18	0.007	0.045	-10000	0	-10000	0	0
IL2RA	-0.029	0.11	-10000	0	-0.36	72	72
IFNG	-0.04	0.098	-10000	0	-0.28	131	131
STAT3 (dimer)	0.031	0.21	-10000	0	-0.64	45	45
HLA-DRB5	-0.025	0.095	-10000	0	-0.32	70	70
FASLG	0.014	0.26	-10000	0	-1.1	29	29
NF kappa B2 p52/RelB	-0.075	0.19	-10000	0	-0.74	49	49
CD4	0	0	-10000	0	-10000	0	0
SOCS1	-0.003	0.038	-10000	0	-0.34	9	9
EntrezGene:6955	-0.006	0.013	-10000	0	-10000	0	0
CD3D	-0.023	0.14	-10000	0	-0.5	56	56
CD3E	-0.021	0.14	-10000	0	-0.53	50	50
CD3G	-0.032	0.16	-10000	0	-0.74	38	38
IL12Rbeta2/JAK2	-0.03	0.16	-10000	0	-0.66	47	47
CCL3	0.018	0.26	-10000	0	-0.93	36	36
CCL4	0.02	0.25	-10000	0	-0.9	33	33
HLA-A	0.009	0.02	-10000	0	-10000	0	0
IL18/IL18R	0.023	0.14	-10000	0	-0.58	44	44
NOS2	0.024	0.24	-10000	0	-0.88	36	36
IL12/IL12R/TYK2/JAK2/SPHK2	-0.002	0.13	-10000	0	-0.36	73	73
IL1R1	0.011	0.28	-10000	0	-1.1	33	33
IL4	-0.005	0.017	-10000	0	-10000	0	0
JAK2	0.016	0.032	-10000	0	-0.84	1	1
EntrezGene:6957	-0.005	0.012	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.029	0.25	-10000	0	-1.1	38	38
RAB7A	0.052	0.19	-10000	0	-0.77	16	16
lysosomal transport	0.053	0.18	-10000	0	-0.72	16	16
FOS	-0.37	0.67	-10000	0	-1.3	293	293
STAT4 (dimer)	0.027	0.26	-10000	0	-0.89	40	40
STAT5A (dimer)	-0.078	0.21	-10000	0	-0.69	61	61
GZMA	0.009	0.28	-10000	0	-1.1	31	31
GZMB	-0.002	0.3	-10000	0	-1.2	36	36
HLX	-0.001	0.013	-10000	0	-10000	0	0
LCK	0.011	0.28	-10000	0	-0.81	59	59
TCR/CD3/MHC II/CD4	-0.065	0.2	-10000	0	-0.57	68	68
IL2/IL2R	-0.028	0.097	-10000	0	-0.47	33	33
MAPK14	0.042	0.22	-10000	0	-0.83	27	27
CCR5	0.031	0.22	-10000	0	-0.85	26	26
IL1B	0.005	0.1	-10000	0	-0.7	16	16
STAT6	0.027	0.085	-10000	0	-0.25	9	9
STAT4	-0.033	0.16	-10000	0	-0.81	37	37
STAT3	0	0	-10000	0	-10000	0	0
STAT1	-0.006	0.04	-10000	0	-0.28	19	19
NFKB1	0	0	-10000	0	-10000	0	0
NFKB2	0	0	-10000	0	-10000	0	0
IL12B	-0.039	0.12	-10000	0	-0.27	176	176
CD8A	-0.001	0.077	-10000	0	-0.38	28	28
CD8B	-0.024	0.16	-10000	0	-0.83	30	30
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.003	0.13	0.36	74	-10000	0	74
IL2RB	-0.012	0.056	-10000	0	-0.28	38	38
proteasomal ubiquitin-dependent protein catabolic process	0.033	0.24	-10000	0	-0.8	40	40
IL2RG	-0.016	0.081	-10000	0	-0.82	5	5
IL12	-0.049	0.17	-10000	0	-0.61	55	55
STAT5A	-0.006	0.072	-10000	0	-0.82	7	7
CD247	-0.015	0.13	-10000	0	-0.62	33	33
IL2	-0.002	0.026	-10000	0	-0.28	8	8
SPHK2	0	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.034	0.2	-10000	0	-0.72	63	63
IL12/IL12R/TYK2/JAK2	0.014	0.28	-10000	0	-0.82	57	57
MAP2K3	0.038	0.22	-10000	0	-0.82	28	28
RIPK2	-0.002	0.021	-10000	0	-0.28	5	5
MAP2K6	0.034	0.22	-10000	0	-0.81	31	31
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.002	0.03	-10000	0	-0.47	3	3
IL18RAP	-0.018	0.16	-10000	0	-0.8	36	36
IL12Rbeta1/TYK2	0.014	0.051	-10000	0	-0.69	1	1
EOMES	-0.021	0.17	-10000	0	-1.5	12	12
STAT1 (dimer)	0.035	0.21	-10000	0	-0.69	34	34
T cell proliferation	0.036	0.19	-10000	0	-0.64	38	38
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.003	0.096	-10000	0	-0.83	12	12
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.058	0.17	-10000	0	-0.75	35	35
ATF2	0.049	0.2	-10000	0	-0.78	25	25

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.034	0.12	-10000	0	-0.62	32	32
FYN	0.016	0.18	-10000	0	-0.77	35	35
LAT/GRAP2/SLP76	-0.027	0.15	-10000	0	-0.66	36	36
IKBKB	-0.001	0.013	-10000	0	-10000	0	0
AKT1	0.031	0.12	-10000	0	-0.48	36	36
B2M	0.008	0.006	-10000	0	-10000	0	0
IKBKG	-0.008	0.026	-10000	0	-0.19	1	1
MAP3K8	-0.005	0.062	-10000	0	-0.82	5	5
mol:Ca2+	-0.026	0.05	-10000	0	-0.12	184	184
integrin-mediated signaling pathway	-0.001	0.026	-10000	0	-0.55	2	2
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.023	0.17	-10000	0	-0.74	36	36
TRPV6	-0.17	0.34	-10000	0	-0.8	198	198
CD28	-0.007	0.066	-10000	0	-0.49	13	13
SHC1	0.011	0.18	-10000	0	-0.83	33	33
receptor internalization	-0.001	0.2	-10000	0	-0.86	39	39
PRF1	-0.001	0.23	-10000	0	-1.1	30	30
KRAS	0	0.009	-10000	0	-10000	0	0
GRB2	0	0.009	-10000	0	-10000	0	0
COT/AKT1	0.033	0.1	-10000	0	-0.39	35	35
LAT	0.009	0.19	-10000	0	-0.81	36	36
EntrezGene:6955	0.001	0.003	-10000	0	-10000	0	0
CD3D	-0.023	0.14	-10000	0	-0.5	56	56
CD3E	-0.018	0.14	-10000	0	-0.52	50	50
CD3G	-0.031	0.16	-10000	0	-0.83	31	31
RASGRP2	-0.006	0.04	-10000	0	-0.18	41	41
RASGRP1	0.038	0.12	-10000	0	-0.48	37	37
HLA-A	0.01	0.019	-10000	0	-10000	0	0
RASSF5	-0.002	0.04	-10000	0	-0.64	3	3
RAP1A/GTP/RAPL	-0.001	0.026	-10000	0	-0.56	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.033	0.042	-10000	0	-0.12	34	34
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.014	0.047	-10000	0	-0.24	22	22
PRKCA	-0.011	0.084	-10000	0	-0.32	46	46
GRAP2	-0.014	0.1	-10000	0	-0.82	14	14
mol:IP3	0.022	0.15	0.27	157	-0.45	35	192
EntrezGene:6957	0.001	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.006	0.21	-10000	0	-0.95	33	33
ORAI1	0.082	0.16	0.39	184	-10000	0	184
CSK	0.009	0.19	-10000	0	-0.85	33	33
B7 family/CD28	-0.02	0.18	-10000	0	-0.75	39	39
CHUK	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.002	0.22	-10000	0	-1	34	34
PTPN6	0.008	0.19	-10000	0	-0.82	35	35
VAV1	0.011	0.18	-10000	0	-0.81	35	35
Monovalent TCR/CD3	-0.029	0.21	-10000	0	-0.71	54	54
CBL	0	0	-10000	0	-10000	0	0
LCK	0.01	0.19	-10000	0	-0.83	36	36
PAG1	0.008	0.19	-10000	0	-0.84	34	34
RAP1A	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.002	0.22	-10000	0	-0.95	36	36
CD80	-0.08	0.12	-10000	0	-0.28	262	262
CD86	-0.002	0.021	-10000	0	-0.28	3	3
PDK1/CARD11/BCL10/MALT1	-0.017	0.057	-10000	0	-0.28	28	28
HRAS	-0.001	0.013	-10000	0	-0.28	2	2
GO:0035030	-0.045	0.13	-10000	0	-0.6	39	39
CD8A	-0.004	0.077	-10000	0	-0.38	28	28
CD8B	-0.024	0.16	-10000	0	-0.83	30	30
PTPRC	-0.009	0.074	-10000	0	-0.83	6	6
PDK1/PKC theta	0.036	0.15	-10000	0	-0.6	38	38
CSK/PAG1	0.014	0.18	-10000	0	-0.81	33	33
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.001	0.011	-10000	0	-10000	0	0
GRAP2/SLP76	-0.034	0.17	-10000	0	-0.79	36	36
STIM1	0.043	0.081	-10000	0	-10000	0	0
RAS family/GTP	0.041	0.053	-10000	0	-0.18	27	27
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.005	0.23	-10000	0	-0.96	39	39
mol:DAG	-0.005	0.1	-10000	0	-0.41	36	36
RAP1A/GDP	0.015	0.018	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
CD247	-0.015	0.13	-10000	0	-0.64	31	31
cytotoxic T cell degranulation	0.002	0.21	-10000	0	-1	30	30
RAP1A/GTP	-0.003	0.014	-10000	0	-0.068	25	25
mol:PI-3-4-5-P3	0.027	0.14	-10000	0	-0.58	36	36
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.016	0.18	0.29	150	-0.61	36	186
NRAS	-0.001	0.013	-10000	0	-0.28	2	2
ZAP70	-0.029	0.13	-10000	0	-0.83	19	19
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.024	0.14	-10000	0	-0.63	36	36
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.033	0.14	-10000	0	-0.6	46	46
CARD11	-0.008	0.055	-10000	0	-0.33	21	21
PRKCB	-0.01	0.086	-10000	0	-0.35	38	38
PRKCE	-0.005	0.069	-10000	0	-0.28	35	35
PRKCQ	0.026	0.18	-10000	0	-0.7	39	39
LCP2	0	0.009	-10000	0	-0.28	1	1
BCL10	0	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.032	0.1	-10000	0	-0.4	36	36
IKK complex	0.042	0.043	-10000	0	-0.12	24	24
RAS family/GDP	-0.002	0.006	-10000	0	-10000	0	0
MAP3K14	0.037	0.079	-10000	0	-0.3	31	31
PDPK1	0.034	0.11	-10000	0	-0.46	34	34
TCR/CD3/MHC I/CD8/Fyn	-0.006	0.24	-10000	0	-0.97	42	42

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.12	0.22	-9999	-0.49	228	228
TC10/GTP	-0.1	0.18	-9999	-0.43	216	216
Insulin Receptor/Insulin/IRS1/Shp2	-0.02	0.1	-9999	-0.52	36	36
HRAS	-0.001	0.013	-9999	-0.28	2	2
APS homodimer	-0.011	0.055	-9999	-0.28	37	37
GRB14	-0.1	0.23	-9999	-0.47	194	194
FOXO3	-0.013	0.062	-9999	-0.72	6	6
AKT1	-0.054	0.12	-9999	-0.4	77	77
INSR	0	0.009	-9999	-10000	0	0
Insulin Receptor/Insulin	-0.003	0.027	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0	0	-9999	-10000	0	0
SORBS1	-0.2	0.35	-9999	-0.82	216	216
CRK	0	0	-9999	-10000	0	0
PTPN1	0.032	0.031	-9999	-10000	0	0
CAV1	-0.12	0.23	-9999	-0.53	207	207
CBL/APS/CAP/Crk-II/C3G	-0.11	0.2	-9999	-0.48	216	216
Insulin Receptor/Insulin/IRS1/NCK2	-0.02	0.1	-9999	-0.52	36	36
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.018	0.089	-9999	-0.45	37	37
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.012	0.056	-9999	-10000	0	0
RPS6KB1	-0.005	0.13	-9999	-0.47	7	7
PARD6A	-0.001	0.016	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.002	-9999	-10000	0	0
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.047	0.11	-9999	-0.49	7	7
HRAS/GTP	-0.016	0.076	-9999	-0.49	2	2
Insulin Receptor	0	0.009	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.019	0.094	-9999	-0.48	36	36
PRKCI	-0.012	0.032	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.059	0.14	-9999	-0.43	105	105
SHC1	0	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0.002	-9999	-10000	0	0
PI3K	-0.019	0.091	-9999	-0.46	37	37
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	0.009	-9999	-10000	0	0
AKT2	-0.054	0.12	-9999	-0.4	78	78
PRKCZ	-0.013	0.038	-9999	-0.62	1	1
SH2B2	-0.011	0.055	-9999	-0.28	37	37
SHC/SHIP	-0.018	0.088	-9999	-0.45	36	36
F2RL2	-0.056	0.14	-9999	-0.34	151	151
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	0.004	-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	-0.51	216	216
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0.003	-9999	-10000	0	0
INPP5D	-0.019	0.095	-9999	-0.49	36	36
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.008	0.068	-9999	-1	4	4
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.033	0.16	-9999	-0.82	36	36
p62DOK/RasGAP	0	0.002	-9999	-10000	0	0
INS	0.003	0.004	-9999	-10000	0	0
mol:PI-3-4-P2	-0.019	0.094	-9999	-0.48	36	36
GRB2	0	0.009	-9999	-10000	0	0
EIF4EBP1	-0.01	0.14	-9999	-0.47	14	14
PTPRA	0	0.001	-9999	-10000	0	0
PIK3CA	0	0.009	-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	0.065	-9999	-0.34	36	36
Insulin Receptor/Insulin/IRS1	-0.021	0.1	-9999	-0.53	36	36
Insulin Receptor/Insulin/IRS3	-0.001	0.007	-9999	-10000	0	0
Par3/Par6	-0.024	0.073	-9999	-0.48	17	17

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.051	0.11	-9999	-0.64	3	3
RAD9A	0	0.009	-9999	-0.28	1	1
AP1	-0.2	0.3	-9999	-0.65	284	284
IFNAR2	0.009	0.006	-9999	-10000	0	0
AKT1	-0.037	0.11	-9999	-0.29	131	131
ER alpha/Oestrogen	-0.12	0.22	-9999	-0.64	131	131
NFX1/SIN3/HDAC complex	0	0.001	-9999	-10000	0	0
EGF	-0.16	0.33	-9999	-0.82	183	183
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	0.084	-9999	-0.6	3	3
SAP18	0	0	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.14	0.14	-9999	-0.28	485	485
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	-0.58	2	2
Mad/Max	0	0.006	-9999	-10000	0	0
TERT	-0.052	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	-0.002	0.026	-9999	-0.28	8	8
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	0.004	-9999	-10000	0	0
CDKN1B	0.006	0.076	-9999	-0.9	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	0.018	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0	0	-9999	-10000	0	0
JUN	-0.008	0.082	-9999	-0.82	9	9
E6	0	0.001	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0	-9999	-10000	0	0
FOS	-0.26	0.38	-9999	-0.82	283	283
IFN-gamma/IRF1	-0.025	0.061	-9999	-0.35	5	5
PARP2	0	0	-9999	-10000	0	0
BLM	-0.031	0.087	-9999	-0.28	101	101
Telomerase	-0.003	0.026	-9999	-10000	0	0
IRF1	-0.002	0.019	-9999	-0.27	3	3
ESR1	-0.15	0.29	-9999	-0.76	149	149
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	0.021	0.007	-9999	-10000	0	0
ABL1	0	0	-9999	-10000	0	0
MXD1	0	0.009	-9999	-0.28	1	1
MRE11A	0	0	-9999	-10000	0	0
HUS1	0	0	-9999	-10000	0	0
RPS6KB1	-0.001	0.016	-9999	-0.28	3	3
TERT/NF kappa B1/14-3-3	-0.062	0.098	-9999	-0.67	3	3
NR2F2	0	0.048	-9999	-0.82	3	3
MAPK3	0.014	0.019	-9999	-10000	0	0
MAPK1	0.014	0.019	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0	0.009	-9999	-0.28	1	1
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	-0.3	0.39	-9999	-0.82	331	331
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.35	0.37	-9999	-0.7	453	453
MYC	-0.014	0.12	-9999	-0.82	20	20
IL2	0.004	0.027	-9999	-0.28	8	8
KU	0	0	-9999	-10000	0	0
RAD50	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-10000	0	0
TGFB1	0	0.009	-9999	-0.28	1	1
TRF2/BLM	-0.017	0.049	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.06	0.083	-9999	-0.64	2	2
SP1/HDAC2	0	0	-9999	-10000	0	0
PINX1	0	0	-9999	-10000	0	0
Telomerase/EST1A	-0.049	0.074	-9999	-0.58	2	2
Smad3/Myc	-0.012	0.08	-9999	-0.55	20	20
911 complex	0	0.004	-9999	-10000	0	0
IFNG	-0.038	0.095	-9999	-10000	0	0
Telomerase/PinX1	-0.049	0.074	-9999	-0.58	2	2
Telomerase/AKT1/mTOR/p70S6K	0.003	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	-0.58	2	2
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	-0.58	2	2
E2F1	-0.082	0.14	-9999	-0.28	292	292
ZNFX1	0	0	-9999	-10000	0	0
PIF1	-0.053	0.11	-9999	-0.28	174	174
NCL	0	0	-9999	-10000	0	0
DKC1	-0.001	0.013	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Syndecan-4-mediated signaling events

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	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	0.033	-9999	-0.66	1	1
positive regulation of JNK cascade	-0.047	0.11	-9999	-0.48	5	5
Syndecan-4/ADAM12	-0.029	0.054	-9999	-0.66	1	1
CCL5	-0.014	0.078	-9999	-0.36	35	35
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	0.02	-9999	-0.28	4	4
ADAM12	-0.022	0.081	-9999	-0.82	2	2
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	-0.001	0.016	-9999	-0.28	3	3
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.056	0.043	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.071	0.14	-9999	-0.54	11	11
Syndecan-4/CXCL12/CXCR4	-0.048	0.11	-9999	-0.55	2	2
Syndecan-4/Laminin alpha3	-0.13	0.2	-9999	-0.5	149	149
MDK	-0.01	0.052	-9999	-10000	0	0
Syndecan-4/FZD7	-0.028	0.07	-9999	-0.54	3	3
Syndecan-4/Midkine	-0.022	0.04	-9999	-0.66	1	1
FZD7	-0.017	0.12	-9999	-0.82	19	19
Syndecan-4/FGFR1/FGF	-0.19	0.22	-9999	-0.54	54	54
THBS1	-0.001	0.027	-9999	-0.82	1	1
integrin-mediated signaling pathway	-0.028	0.071	-9999	-0.5	12	12
positive regulation of MAPKKK cascade	-0.047	0.11	-9999	-0.48	5	5
Syndecan-4/TACI	-0.03	0.068	-9999	-0.53	5	5
CXCR4	-0.008	0.046	-9999	-10000	0	0
cell adhesion	-0.025	0.055	-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	-0.025	0.051	-9999	-0.52	5	5
ITGB1	0	0	-9999	-10000	0	0
LAMA1	-0.096	0.26	-9999	-0.82	106	106
LAMA3	-0.2	0.36	-9999	-0.82	227	227
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.005	0.12	-9999	-0.74	23	23
Syndecan-4/alpha-Actinin	-0.02	0.036	-9999	-0.56	2	2
TFPI	-0.035	0.17	-9999	-0.82	39	39
F2	0.001	0.025	-9999	-10000	0	0
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.16	0.24	-9999	-0.6	100	100
ACTN1	-0.001	0.027	-9999	-0.82	1	1
TNC	-0.019	0.12	-9999	-0.71	24	24
Syndecan-4/CXCL12	-0.052	0.12	-9999	-0.48	23	23
FGF6	-0.002	0.039	-9999	-0.82	2	2
RHOA	0	0	-9999	-10000	0	0
CXCL12	-0.06	0.22	-9999	-0.82	67	67
TNFRSF13B	-0.025	0.12	-9999	-0.82	14	14
FGF2	-0.33	0.4	-9999	-0.82	370	370
FGFR1	-0.01	0.087	-9999	-0.73	12	12
Syndecan-4/PI-4-5-P2	-0.014	0.044	-9999	-0.66	1	1
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.12	0.15	-9999	-0.29	202	202
cell migration	-0.025	0.019	-9999	-10000	0	0
PRKCD	0.004	0.013	-9999	-0.27	1	1
vasculogenesis	-0.019	0.035	-9999	-0.63	1	1
SDC4	-0.014	0.046	-9999	-0.7	1	1
Syndecan-4/Tenascin C	-0.029	0.074	-9999	-0.52	11	11
Syndecan-4/PI-4-5-P2/PKC alpha	-0.044	0.034	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.019	0.033	-9999	-0.66	1	1
MMP9	-0.12	0.14	-9999	-0.28	408	408
Rac1/GTP	-0.026	0.056	-9999	-0.36	21	21
cytoskeleton organization	-0.019	0.032	-9999	-0.63	1	1
GIPC1	0	0.009	-9999	-10000	0	0
Syndecan-4/TFPI	-0.038	0.095	-9999	-0.52	10	10

×

Coregulation of Androgen receptor activity

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.004	0.035	-10000	0	-0.82	1	1
SVIL	-0.009	0.05	-10000	0	-0.82	3	3
ZNF318	0.024	0.06	-10000	0	-10000	0	0
JMJD2C	-0.004	0.043	-10000	0	-0.13	89	89
T-DHT/AR/Ubc9	-0.076	0.18	-10000	0	-0.57	104	104
CARM1	0	0	-10000	0	-10000	0	0
PRDX1	0.003	0.007	-10000	0	-10000	0	0
PELP1	0.005	0.013	-10000	0	-10000	0	0
CTNNB1	-0.005	0.013	-10000	0	-10000	0	0
AKT1	0.008	0.019	-10000	0	-10000	0	0
PTK2B	-0.004	0.011	-10000	0	-10000	0	0
MED1	0.002	0.048	-10000	0	-0.28	19	19
MAK	0.013	0.11	0.28	1	-0.8	10	11
response to oxidative stress	0.001	0.004	-10000	0	-10000	0	0
HIP1	-0.01	0.057	-10000	0	-0.82	4	4
GSN	-0.015	0.1	-10000	0	-0.82	13	13
NCOA2	-0.015	0.11	-10000	0	-0.83	17	17
NCOA6	-0.002	0.021	-10000	0	-0.28	1	1
DNA-PK	0.023	0.061	-10000	0	-10000	0	0
NCOA4	0	0	-10000	0	-10000	0	0
PIAS3	-0.005	0.013	-10000	0	-10000	0	0
cell proliferation	-0.006	0.11	-10000	0	-0.87	10	10
XRCC5	0.007	0.016	-10000	0	-10000	0	0
UBE3A	-0.007	0.032	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.089	0.21	-10000	0	-0.61	117	117
FHL2	-0.016	0.12	-10000	0	-1.3	5	5
RANBP9	-0.002	0.019	-10000	0	-10000	0	0
JMJD1A	-0.012	0.057	-10000	0	-0.14	138	138
CDK6	-0.006	0.078	-10000	0	-0.72	10	10
TGFB1I1	-0.009	0.05	-10000	0	-0.82	3	3
T-DHT/AR/CyclinD1	-0.088	0.19	-10000	0	-0.58	107	107
XRCC6	0.007	0.016	-10000	0	-10000	0	0
T-DHT/AR	-0.063	0.21	-10000	0	-0.56	120	120
CTDSP1	0	0	-10000	0	-10000	0	0
CTDSP2	0.016	0.041	-10000	0	-10000	0	0
BRCA1	-0.007	0.023	-10000	0	-0.36	1	1
TCF4	0.007	0.074	-10000	0	-0.82	6	6
CDKN2A	-0.036	0.1	-10000	0	-10000	0	0
SRF	0.024	0.02	-10000	0	-10000	0	0
NKX3-1	-0.083	0.2	-10000	0	-1.2	20	20
KLK3	-0.2	0.54	-10000	0	-1.6	121	121
TMF1	0	0	-10000	0	-10000	0	0
HNRNPA1	0.009	0.022	-10000	0	-10000	0	0
AOF2	-0.009	0.025	-10000	0	-0.072	121	121
APPL1	0.035	0.034	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.067	0.19	-10000	0	-0.57	104	104
AR	-0.092	0.27	-10000	0	-0.83	105	105
UBA3	0	0	-10000	0	-10000	0	0
PATZ1	0.009	0.022	-10000	0	-10000	0	0
PAWR	-0.001	0.027	-10000	0	-0.82	1	1
PRKDC	0.005	0.024	-10000	0	-10000	0	0
PA2G4	0.012	0.029	-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	104	104
RPS6KA3	-0.006	0.052	-10000	0	-0.82	3	3
T-DHT/AR/ARA70	-0.08	0.18	-10000	0	-0.57	104	104
LATS2	0.01	0.024	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.058	0.18	-10000	0	-0.52	104	104
Cyclin D3/CDK11 p58	0	0.006	-10000	0	-10000	0	0
VAV3	-0.016	0.077	-10000	0	-0.71	8	8
KLK2	-0.12	0.34	-10000	0	-1.2	76	76
CASP8	0.004	0.011	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.081	0.18	-10000	0	-0.54	117	117
TMPRSS2	-0.18	0.4	-10000	0	-1.2	119	119
CCND1	-0.016	0.072	-10000	0	-0.33	38	38
PIAS1	-0.007	0.032	-10000	0	-10000	0	0
mol:T-DHT	-0.009	0.035	-10000	0	-0.08	166	166
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.014	0.052	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.078	0.19	-10000	0	-0.57	112	112
CMTM2	0.003	0.013	-10000	0	-0.28	1	1
SNURF	-0.021	0.13	-10000	0	-0.82	23	23
ZMIZ1	0.003	0.032	-10000	0	-0.35	1	1
CCND3	0.001	0.011	-10000	0	-0.28	1	1
TGIF1	0.009	0.022	-10000	0	-10000	0	0
FKBP4	-0.004	0.032	-10000	0	-0.29	7	7

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.027	0.027	-9999	-10000	0	0
BUB1B	-0.037	0.047	-9999	-10000	0	0
PLK1	-0.007	0.021	-9999	-10000	0	0
PLK1S1	0.001	0.013	-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	-0.26	462	462
WEE1	-0.001	0.022	-9999	-10000	0	0
cytokinesis	-0.045	0.047	-9999	-0.26	5	5
PP2A-alpha B56	0.034	0.022	-9999	-10000	0	0
AURKA	0.003	0.011	-9999	-10000	0	0
PICH/PLK1	-0.074	0.092	-9999	-0.32	11	11
CENPE	-0.051	0.083	-9999	-0.2	2	2
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	-10000	0	0
SPC24	-0.17	0.14	-9999	-0.28	562	562
FBXW11	0	0	-9999	-10000	0	0
CLSPN	-0.002	0.015	-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	-0.001	0.002	-9999	-10000	0	0
STAG2	-0.001	0.027	-9999	-0.82	1	1
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	0.029	0.019	-9999	-10000	0	0
TPT1	0.001	0.013	-9999	-10000	0	0
CDC25C	-0.002	0.013	-9999	-10000	0	0
CDC25B	-0.003	0.038	-9999	-0.28	17	17
SGOL1	-0.027	0.027	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.021	0.04	-9999	-10000	0	0
CDC14B	-0.009	0.11	-9999	-0.65	27	27
CDC20	-0.15	0.14	-9999	-10000	0	0
PLK1/PBIP1	-0.029	0.053	-9999	-10000	0	0
mitosis	-0.007	0.007	-9999	-0.022	2	2
FBXO5	0.001	0.021	-9999	-10000	0	0
CDC2	-0.001	0.002	-9999	-10000	0	0
NDC80	-0.18	0.13	-9999	-0.28	592	592
metaphase plate congression	-0.002	0.014	-9999	-10000	0	0
ERCC6L	-0.065	0.084	-9999	-10000	0	0
NLP/gamma Tubulin	0	0.012	-9999	-10000	0	0
microtubule cytoskeleton organization	0.001	0.013	-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	0.095	-9999	-0.27	246	246
GRASP65/GM130/RAB1/GTP/PLK1	-0.001	0.003	-9999	-10000	0	0
RAB1A	0	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	-0.001	0.022	-9999	-10000	0	0
mitotic prometaphase	-0.002	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.01	0.049	-9999	-0.3	12	12
microtubule-based process	-0.11	0.061	-9999	-0.2	2	2
Golgi organization	-0.007	0.021	-9999	-10000	0	0
Cohesin/SA2	-0.008	0.018	-9999	-0.48	1	1
PPP1CB/MYPT1	0	0	-9999	-10000	0	0
KIF20A	-0.22	0.12	-9999	-10000	0	0
APC/C/CDC20	-0.084	0.075	-9999	-0.2	2	2
PPP2R1A	0	0	-9999	-10000	0	0
chromosome segregation	-0.029	0.052	-9999	-10000	0	0
PRC1	-0.076	0.12	-9999	-0.28	248	248
ECT2	-0.003	0.038	-9999	-10000	0	0
C13orf34	0.001	0.02	-9999	-10000	0	0
NUDC	-0.002	0.014	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.037	0.047	-9999	-10000	0	0
spindle assembly	-0.002	0.018	-9999	-10000	0	0
spindle stabilization	0.001	0.013	-9999	-10000	0	0
APC/C/HCDH1	-0.017	0.095	-9999	-0.56	27	27
MKLP2/PLK1	-0.11	0.061	-9999	-0.2	2	2
CCNB1	-0.062	0.12	-9999	-0.28	207	207
PPP1CB	0	0	-9999	-10000	0	0
BTRC	0	0	-9999	-10000	0	0
ROCK2	0.001	0.057	-9999	-0.52	10	10
TUBG1	0.001	0.013	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.021	0.039	-9999	-10000	0	0
MLF1IP	-0.03	0.075	-9999	-10000	0	0
INCENP	0	0	-9999	-10000	0	0

×

BCR signaling pathway

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.004	0.11	-10000	0	-0.46	30	30
IKBKB	0.015	0.054	-10000	0	-0.26	3	3
AKT1	0.005	0.08	0.25	1	-0.28	16	17
IKBKG	0.018	0.056	-10000	0	-0.28	3	3
CALM1	-0.012	0.096	-10000	0	-0.46	27	27
PIK3CA	0	0.009	-10000	0	-10000	0	0
MAP3K1	-0.009	0.15	-10000	0	-0.68	27	27
MAP3K7	0	0.009	-10000	0	-10000	0	0
mol:Ca2+	-0.021	0.1	-10000	0	-0.49	27	27
DOK1	0	0.009	-10000	0	-10000	0	0
AP-1	-0.045	0.11	-10000	0	-0.26	75	75
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	-0.08	0.22	-10000	0	-0.67	96	96
CD22	-0.062	0.19	-10000	0	-0.56	85	85
CAMK2G	-0.003	0.09	-10000	0	-0.51	15	15
CSNK2A1	0	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.049	0.14	-10000	0	-0.81	15	15
GO:0007205	-0.021	0.1	-10000	0	-0.5	27	27
SYK	0	0.009	-10000	0	-0.28	1	1
ELK1	-0.012	0.097	-10000	0	-0.47	27	27
NFATC1	-0.016	0.13	-10000	0	-0.57	28	28
B-cell antigen/BCR complex	-0.08	0.22	-10000	0	-0.67	96	96
PAG1/CSK	-0.001	0.013	-10000	0	-10000	0	0
NFKBIB	0.015	0.02	-10000	0	-10000	0	0
HRAS	-0.009	0.11	-10000	0	-0.49	27	27
NFKBIA	0.015	0.019	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.019	0.016	-10000	0	-10000	0	0
RasGAP/Csk	-0.059	0.17	-10000	0	-0.55	84	84
mol:GDP	-0.021	0.095	-10000	0	-0.47	27	27
PTEN	-0.002	0.039	-10000	0	-0.82	2	2
CD79B	-0.029	0.14	-10000	0	-0.63	42	42
NF-kappa-B/RelA/I kappa B alpha	0.019	0.016	-10000	0	-10000	0	0
GRB2	0	0.009	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.024	0.16	-10000	0	-0.48	82	82
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
mol:IP3	-0.03	0.1	-10000	0	-0.51	27	27
CSK	0	0	-10000	0	-10000	0	0
FOS	-0.14	0.23	-10000	0	-0.46	302	302
CHUK	0.018	0.056	-10000	0	-0.24	16	16
IBTK	0	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.024	0.081	-10000	0	-0.49	16	16
PTPN6	-0.057	0.17	-10000	0	-0.52	85	85
RELA	0	0	-10000	0	-10000	0	0
BCL2A1	0.015	0.02	-10000	0	-0.12	1	1
VAV2	-0.07	0.17	-10000	0	-0.84	28	28
ubiquitin-dependent protein catabolic process	0.019	0.019	-10000	0	-10000	0	0
BTK	-0.004	0.006	-10000	0	-10000	0	0
CD19	-0.08	0.18	-10000	0	-0.56	82	82
MAP4K1	-0.012	0.064	-10000	0	-0.82	2	2
CD72	-0.008	0.051	-10000	0	-0.3	23	23
PAG1	-0.002	0.021	-10000	0	-10000	0	0
MAPK14	0.002	0.13	-10000	0	-0.55	27	27
SH3BP5	0	0	-10000	0	-10000	0	0
PIK3AP1	-0.012	0.11	-10000	0	-0.55	27	27
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.042	0.14	-10000	0	-0.49	71	71
RAF1	-0.001	0.1	-10000	0	-0.45	27	27
RasGAP/p62DOK/SHIP	-0.056	0.16	-10000	0	-0.52	84	84
CD79A	-0.082	0.22	-10000	0	-0.57	133	133
re-entry into mitotic cell cycle	-0.045	0.11	-10000	0	-0.26	71	71
RASA1	0	0	-10000	0	-10000	0	0
MAPK3	0.015	0.085	-10000	0	-0.44	15	15
MAPK1	0.015	0.085	-10000	0	-0.44	15	15
CD72/SHP1	-0.054	0.16	-10000	0	-0.7	35	35
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	0.001	0.13	-10000	0	-0.54	30	30
actin cytoskeleton organization	-0.025	0.15	-10000	0	-0.67	28	28
NF-kappa-B/RelA	0.042	0.031	-10000	0	-10000	0	0
Calcineurin	-0.021	0.074	-10000	0	-0.45	15	15
PI3K	-0.055	0.13	-10000	0	-0.55	31	31
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.033	0.11	-10000	0	-0.58	27	27
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.054	0.17	-10000	0	-0.85	31	31
DAPP1	-0.053	0.2	-10000	0	-1	30	30
cytokine secretion	-0.014	0.12	-10000	0	-0.52	29	29
mol:DAG	-0.03	0.1	-10000	0	-0.51	27	27
PLCG2	-0.001	0.029	-10000	0	-0.55	2	2
MAP2K1	0.007	0.093	-10000	0	-0.5	15	15
B-cell antigen/BCR complex/FcgammaRIIB	-0.071	0.2	-10000	0	-0.64	84	84
mol:PI-3-4-5-P3	-0.041	0.091	0.35	1	-0.37	30	31
ETS1	0.004	0.087	-10000	0	-0.47	16	16
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.058	0.17	-10000	0	-0.55	82	82
B-cell antigen/BCR complex/LYN	-0.059	0.2	-10000	0	-0.6	82	82
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
RAC1	-0.029	0.17	-10000	0	-0.74	28	28
B-cell antigen/BCR complex/LYN/SYK	-0.058	0.18	-10000	0	-0.57	84	84
CARD11	-0.016	0.1	-10000	0	-0.5	27	27
FCGR2B	-0.003	0.048	-10000	0	-0.69	4	4
PPP3CA	0	0.009	-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	-0.009	0.074	-10000	0	-0.82	6	6
PDPK1	-0.026	0.061	0.22	1	-0.28	16	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

×

Regulation of Androgen receptor activity

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.02	0.006	-9999	-10000	0	0
SMARCC1	0.004	0.021	-9999	-0.58	1	1
REL	0	0.062	-9999	-0.82	5	5
HDAC7	0.009	0.13	-9999	-0.63	11	11
JUN	-0.008	0.081	-9999	-0.82	9	9
EP300	0	0	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
KAT5	0.002	0.004	-9999	-10000	0	0
MAPK14	0.004	0.1	-9999	-0.64	21	21
FOXO1	-0.007	0.077	-9999	-0.83	8	8
T-DHT/AR	-0.005	0.14	-9999	-0.54	25	25
MAP2K6	-0.019	0.12	-9999	-0.81	22	22
BRM/BAF57	-0.001	0.011	-9999	-10000	0	0
MAP2K4	0	0.028	-9999	-0.83	1	1
SMARCA2	0	0	-9999	-10000	0	0
PDE9A	-0.094	0.3	-9999	-1.2	57	57
NCOA2	-0.015	0.11	-9999	-0.82	17	17
CEBPA	-0.006	0.077	-9999	-0.82	8	8
EHMT2	0	0	-9999	-10000	0	0
cell proliferation	0.016	0.14	-9999	-0.52	18	18
NR0B1	-0.01	0.051	-9999	-0.28	32	32
EGR1	-0.27	0.39	-9999	-0.83	295	295
RXRs/9cRA	-0.13	0.22	-9999	-0.51	232	232
AR/RACK1/Src	-0.005	0.11	-9999	-0.5	24	24
AR/GR	-0.047	0.12	-9999	-0.44	37	37
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	0.017	0.046	-9999	-0.64	4	4
T-DHT/AR/TIF2/CARM1	-0.035	0.12	-9999	-0.52	38	38
SRC	0.021	0.093	-9999	-0.5	24	24
NR3C1	-0.009	0.086	-9999	-0.82	10	10
KLK3	-0.22	0.44	-9999	-1.2	145	145
APPBP2	-0.001	0.016	-9999	-10000	0	0
TRIM24	0	0.009	-9999	-0.28	1	1
T-DHT/AR/TIP60	-0.026	0.096	-9999	-0.53	24	24
TMPRSS2	-0.17	0.43	-9999	-1.3	120	120
RXRG	-0.21	0.36	-9999	-0.83	232	232
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	-0.004	0.054	-9999	-0.82	4	4
KLK2	-0.04	0.25	-9999	-0.78	87	87
AR	-0.023	0.13	-9999	-0.34	112	112
SENP1	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-10000	0	0
MDM2	0.004	0.023	-9999	-10000	0	0
SRY	0.004	0.01	-9999	-10000	0	0
GATA2	-0.024	0.13	-9999	-0.82	23	23
MYST2	0.001	0.01	-9999	-0.28	1	1
HOXB13	-0.13	0.14	-9999	-0.31	63	63
T-DHT/AR/RACK1/Src	-0.026	0.094	-9999	-0.51	24	24
positive regulation of transcription	-0.024	0.13	-9999	-0.82	23	23
DNAJA1	0	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.013	-9999	-10000	0	0
NCOA1	0.011	0.029	-9999	-0.85	1	1
SPDEF	-0.05	0.2	-9999	-0.69	72	72
T-DHT/AR/TIF2	0.021	0.081	-9999	-0.53	6	6
T-DHT/AR/Hsp90	-0.032	0.092	-9999	-0.53	24	24
GSK3B	0.001	0.004	-9999	-10000	0	0
NR2C1	0.002	0.006	-9999	-10000	0	0
mol:T-DHT	0.014	0.099	-9999	-0.54	24	24
SIRT1	0	0	-9999	-10000	0	0
ZMIZ2	0.006	0.014	-9999	-10000	0	0
POU2F1	0.02	0.027	-9999	-0.41	1	1
T-DHT/AR/DAX-1	-0.034	0.096	-9999	-0.54	24	24
CREBBP	0	0	-9999	-10000	0	0
SMARCE1	-0.001	0.016	-9999	-0.3	1	1

×

Regulation of nuclear SMAD2/3 signaling

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	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	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.1	0.21	-10000	0	-0.59	131	131
AKT1	0.013	0.005	-10000	0	-10000	0	0
GSC	-0.047	0.32	-10000	0	-1.5	41	41
NKX2-5	-0.039	0.096	-10000	0	-0.27	131	131
muscle cell differentiation	0.005	0.042	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1	0.003	0.03	-10000	0	-10000	0	0
SMAD4	0.013	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	-0.22	0.27	-10000	0	-0.55	365	365
SMAD3/SMAD4/VDR	0.006	0.029	-10000	0	-0.48	1	1
MYC	-0.018	0.12	-10000	0	-0.83	20	20
CDKN2B	0.03	0.12	-10000	0	-1.5	5	5
AP1	-0.13	0.22	-10000	0	-0.44	263	263
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	0.039	-10000	0	-0.33	2	2
SP3	0	0	-10000	0	-10000	0	0
CREB1	0	0	-10000	0	-10000	0	0
FOXH1	-0.046	0.099	-10000	0	-0.4	4	4
SMAD3/SMAD4/GR	-0.008	0.066	-10000	0	-0.6	10	10
GATA3	-0.038	0.16	-10000	0	-0.57	60	60
SKI/SIN3/HDAC complex/NCoR1	0.002	0.012	-10000	0	-10000	0	0
MEF2C/TIF2	-0.037	0.09	-10000	0	-0.54	19	19
endothelial cell migration	-0.01	0.036	-10000	0	-10000	0	0
MAX	0.001	0.004	-10000	0	-10000	0	0
RBBP7	-0.002	0.026	-10000	0	-0.28	8	8
RBBP4	0	0	-10000	0	-10000	0	0
RUNX2	-0.004	0.032	-10000	0	-0.28	12	12
RUNX3	-0.004	0.056	-10000	0	-0.82	4	4
RUNX1	-0.001	0.027	-10000	0	-0.82	1	1
CTBP1	0	0	-10000	0	-10000	0	0
NR3C1	-0.008	0.086	-10000	0	-0.83	10	10
VDR	0	0	-10000	0	-10000	0	0
CDKN1A	0.05	0.063	-10000	0	-1.4	1	1
KAT2B	0.001	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.02	0.069	-10000	0	-0.42	4	4
DCP1A	0	0	-10000	0	-10000	0	0
SKI	0	0	-10000	0	-10000	0	0
SERPINE1	0.01	0.036	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF2	-0.002	0.029	-10000	0	-0.56	1	1
SMAD3/SMAD4/ATF3	-0.088	0.21	-10000	0	-0.59	137	137
SAP30	-0.001	0.018	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.006	0.024	-10000	0	-10000	0	0
JUN	-0.089	0.24	-10000	0	-0.46	164	164
SMAD3/SMAD4/IRF7	-0.009	0.057	-10000	0	-10000	0	0
TFE3	0.016	0.007	-10000	0	-10000	0	0
COL1A2	0.029	0.091	-10000	0	-1.2	1	1
mesenchymal cell differentiation	0.003	0.028	-10000	0	-10000	0	0
DLX1	-0.051	0.13	-10000	0	-0.82	9	9
TCF3	0	0	-10000	0	-10000	0	0
FOS	-0.24	0.39	-10000	0	-0.82	283	283
SMAD3/SMAD4/Max	-0.002	0.023	-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	0.042	0.046	-10000	0	-0.81	1	1
TGIF2/HDAC complex/SMAD3/SMAD4	-0.001	0.023	-10000	0	-10000	0	0
IRF7	-0.022	0.075	-10000	0	-0.35	17	17
ESR1	-0.15	0.29	-10000	0	-0.57	247	247
HNF4A	-0.004	0.033	-10000	0	-10000	0	0
MEF2C	0	0.086	-10000	0	-0.57	3	3
SMAD2-3/SMAD4	-0.002	0.029	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.003	0.024	-10000	0	-0.55	1	1
IGHV3OR16-13	-0.001	0.009	-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	-0.003	0.03	-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	0.025	-10000	0	-10000	0	0
MSG1/HSC70	-0.26	0.31	-10000	0	-0.63	365	365
SMAD2	0.014	0.022	-10000	0	-10000	0	0
SMAD3	0.013	0.029	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.006	0.021	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.028	0.02	-10000	0	-10000	0	0
NCOR1	-0.001	0.027	-10000	0	-0.83	1	1
NCOA2	-0.015	0.11	-10000	0	-0.82	17	17
NCOA1	-0.001	0.027	-10000	0	-0.82	1	1
MYOD/E2A	-0.002	0.019	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.008	0.034	-10000	0	-10000	0	0
IFNB1	0.016	0.08	-10000	0	-0.4	10	10
SMAD3/SMAD4/MEF2C	-0.023	0.067	-10000	0	-0.9	1	1
CITED1	-0.33	0.4	-10000	0	-0.81	377	377
SMAD2-3/SMAD4/ARC105	0	0.025	-10000	0	-10000	0	0
RBL1	-0.001	0.013	-10000	0	-0.28	2	2
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.021	0.058	-10000	0	-0.49	5	5
RUNX1-3/PEBPB2	-0.003	0.047	-10000	0	-0.67	4	4
SMAD7	-0.082	0.14	-10000	0	-0.56	8	8
MYC/MIZ-1	-0.013	0.094	-10000	0	-0.64	20	20
SMAD3/SMAD4	0.02	0.06	0.27	38	-10000	0	38
IL10	0.016	0.12	-10000	0	-0.53	35	35
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	0.012	0.12	-10000	0	-0.52	33	33
CDK4	0.001	0.016	-10000	0	-0.28	2	2
PIAS4	0.001	0.003	-10000	0	-10000	0	0
ATF3	-0.12	0.3	-10000	0	-0.82	137	137
SMAD3/SMAD4/SP1	0.001	0.024	-10000	0	-10000	0	0
FOXG1	-0.02	0.071	-10000	0	-0.28	64	64
FOXO3	0.025	0.032	-10000	0	-0.63	2	2
FOXO1	0.02	0.062	-10000	0	-0.63	8	8
FOXO4	0.026	0.007	-10000	0	-10000	0	0
heart looping	0	0.086	-10000	0	-0.57	3	3
CEBPB	0.008	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.028	0.08	-10000	0	-0.59	9	9
MYOD1	-0.003	0.03	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.006	0.029	-10000	0	-10000	0	0
SMAD3/SMAD4/GATA3	-0.024	0.12	-10000	0	-0.59	33	33
SnoN/SIN3/HDAC complex/NCoR1	-0.003	0.03	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.001	0.048	-10000	0	-0.63	4	4
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	-0.007	0.084	-10000	0	-0.42	5	5
ITGB5	0.051	0.042	-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	-0.59	104	104
AR	-0.094	0.26	-10000	0	-0.82	104	104
negative regulation of cell growth	-0.027	0.074	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.006	0.029	-10000	0	-10000	0	0
E2F5	-0.006	0.041	-10000	0	-0.28	20	20
E2F4	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0	0.052	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	0.001	0.042	-10000	0	-0.34	5	5
TFDP1	-0.001	0.018	-10000	0	-0.28	4	4
SMAD3/SMAD4/AP1	-0.13	0.22	-10000	0	-0.48	132	132
SMAD3/SMAD4/RUNX2	-0.003	0.028	-10000	0	-10000	0	0
TGIF2	0	0	-10000	0	-10000	0	0
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	-0.001	0.027	-10000	0	-0.82	1	1

×

Thromboxane A2 receptor signaling

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
TGM2	0.001	0.036	-10000	0	-10000	0	0
GNB1/GNG2	-0.014	0.046	-10000	0	-0.2	30	30
AKT1	0.052	0.07	-10000	0	-0.2	51	51
EGF	-0.16	0.33	-10000	0	-0.82	183	183
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	-0.009	0.049	-10000	0	-0.43	3	3
mol:Ca2+	0.049	0.096	-10000	0	-0.3	51	51
LYN	-0.009	0.045	-10000	0	-0.33	2	2
RhoA/GTP	-0.008	0.029	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.055	0.11	-10000	0	-0.34	51	51
GNG2	-0.006	0.072	-10000	0	-0.83	7	7
ARRB2	0	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.03	0.056	-10000	0	-0.55	6	6
G beta5/gamma2	-0.018	0.061	-10000	0	-0.27	28	28
PRKCH	0.051	0.11	-10000	0	-0.35	51	51
DNM1	-0.005	0.062	-10000	0	-0.73	6	6
TXA2/TP beta/beta Arrestin3	-0.003	0.025	-10000	0	-0.31	5	5
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.027	0.14	-10000	0	-0.72	35	35
G12 family/GTP	-0.02	0.071	-10000	0	-0.3	51	51
ADRBK1	0	0	-10000	0	-10000	0	0
ADRBK2	-0.003	0.047	-10000	0	-0.83	3	3
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.039	0.075	0.35	15	-10000	0	15
mol:NADP	0	0	-10000	0	-10000	0	0
RAB11A	-0.001	0.013	-10000	0	-0.28	2	2
PRKG1	-0.039	0.18	-10000	0	-0.82	43	43
mol:IP3	0.051	0.12	-10000	0	-0.38	51	51
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	0.049	0.15	-10000	0	-0.51	51	51
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.001	0.061	-10000	0	-0.39	7	7
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.008	0.046	-10000	0	-0.33	3	3
RHOA	0	0	-10000	0	-10000	0	0
PTGIR	-0.002	0.022	-10000	0	-10000	0	0
PRKCB1	0.048	0.11	-10000	0	-0.37	51	51
GNAQ	-0.002	0.039	-10000	0	-0.82	2	2
mol:L-citrulline	0	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.051	0.15	-10000	0	-0.54	51	51
LCK	-0.011	0.069	-10000	0	-0.45	13	13
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.011	0.054	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.025	0.029	-10000	0	-0.3	3	3
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.01	0.053	-10000	0	-10000	0	0
MAPK14	0.053	0.076	-10000	0	-0.22	51	51
TGM2/GTP	0.051	0.13	-10000	0	-0.42	51	51
MAPK11	0.053	0.079	-10000	0	-0.23	51	51
ARHGEF1	0.04	0.059	-10000	0	-0.19	14	14
GNAI2	0	0	-10000	0	-10000	0	0
JNK cascade	0.052	0.12	-10000	0	-0.39	51	51
RAB11/GDP	-0.001	0.013	-10000	0	-0.28	2	2
ICAM1	0.048	0.09	-10000	0	-0.28	51	51
cAMP biosynthetic process	0.047	0.11	-10000	0	-0.35	51	51
Gq family/GTP/EBP50	-0.006	0.031	-10000	0	-0.25	13	13
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.009	0.045	-10000	0	-0.33	2	2
GNB5	0	0	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
EGF/EGFR	-0.028	0.1	-10000	0	-0.31	34	34
VCAM1	0.047	0.097	-10000	0	-0.31	51	51
TP beta/Gq family/GDP/G beta5/gamma2	0.03	0.056	-10000	0	-0.55	6	6
platelet activation	0.069	0.1	-10000	0	-0.3	51	51
PGI2/IP	-0.001	0.015	-10000	0	-10000	0	0
PRKACA	-0.013	0.066	-10000	0	-0.38	28	28
Gq family/GDP/G beta5/gamma2	0.027	0.057	-10000	0	-0.55	6	6
TXA2/TP beta/beta Arrestin2	-0.005	0.049	-10000	0	-0.66	5	5
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.012	0.061	-10000	0	-0.36	28	28
mol:DAG	0.05	0.12	-10000	0	-0.42	51	51
EGFR	-0.3	0.4	-10000	0	-0.82	331	331
TXA2/TP alpha	0.052	0.14	-10000	0	-0.48	51	51
Gq family/GTP	-0.004	0.034	-10000	0	-0.28	13	13
YES1	-0.009	0.047	-10000	0	-0.35	3	3
GNAI2/GTP	-0.01	0.052	-10000	0	-0.38	3	3
PGD2/DP	-0.021	0.11	-10000	0	-0.64	28	28
SLC9A3R1	-0.024	0.079	-10000	0	-0.28	80	80
FYN	-0.009	0.047	-10000	0	-0.35	3	3
mol:NO	0	0	-10000	0	-10000	0	0
GNA15	-0.003	0.035	-10000	0	-0.36	7	7
PGK/cGMP	-0.026	0.12	-10000	0	-0.56	43	43
RhoA/GDP	0	0	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.011	0.07	-10000	0	-0.54	7	7
NOS3	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	0.045	0.12	-10000	0	-0.36	65	65
PRKCB	0.046	0.12	-10000	0	-0.37	61	61
PRKCE	0.052	0.11	-10000	0	-0.34	52	52
PRKCD	0.051	0.11	-10000	0	-0.38	51	51
PRKCG	0.047	0.12	-10000	0	-0.38	51	51
muscle contraction	0.054	0.15	-10000	0	-0.49	51	51
PRKCZ	0.055	0.11	-10000	0	-0.34	52	52
ARR3	-0.002	0.024	-10000	0	-0.28	7	7
TXA2/TP beta	-0.011	0.058	-10000	0	-0.43	3	3
PRKCQ	0.04	0.13	-10000	0	-0.37	75	75
MAPKKK cascade	0.048	0.14	-10000	0	-0.46	52	52
SELE	0.04	0.12	-10000	0	-0.42	51	51
TP beta/GNAI2/GDP/G beta/gamma	-0.013	0.069	-10000	0	-0.54	7	7
ROCK1	0	0	-10000	0	-10000	0	0
GNA14	-0.014	0.087	-10000	0	-0.42	30	30
chemotaxis	0.05	0.17	-10000	0	-0.62	51	51
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	-0.002	0.039	-10000	0	-0.82	2	2
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.019	0.12	-9999	-0.8	22	22
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	-0.001	0.027	-9999	-0.82	1	1
RAC1-CDC42/GTP/PAK family	-0.13	0.14	-9999	-0.28	421	421
response to UV	0	0	-9999	-10000	0	0
YES1	-0.001	0.027	-9999	-0.82	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	0.027	-9999	-0.82	1	1
MAP3K12	0	0	-9999	-10000	0	0
FGR	-0.001	0.029	-9999	-0.82	1	1
p38 alpha/TAB1	-0.007	0.035	-9999	-0.33	3	3
PRKG1	-0.039	0.18	-9999	-0.82	43	43
DUSP8	-0.003	0.048	-9999	-0.82	3	3
PGK/cGMP/p38 alpha	-0.026	0.093	-9999	-0.42	45	45
apoptosis	-0.007	0.034	-9999	-0.32	3	3
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0	0	-9999	-10000	0	0
DUSP1	-0.11	0.28	-9999	-0.82	124	124
PAK1	-0.006	0.041	-9999	-10000	0	0
SRC	0	0.009	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0.005	-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	0.009	-9999	-0.28	1	1
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.016	0.07	-9999	-0.36	17	17
BLK	-0.039	0.1	-9999	-0.82	3	3
HCK	-0.004	0.032	-9999	-0.28	12	12
MAP2K3	0	0.009	-9999	-0.28	1	1
DUSP16	0	0	-9999	-10000	0	0
DUSP10	-0.001	0.013	-9999	-10000	0	0
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.027	0.049	-9999	-0.36	3	3
positive regulation of innate immune response	0.022	0.076	-9999	-0.37	17	17
LCK	-0.018	0.1	-9999	-0.43	39	39
p38alpha-beta/MKP7	-0.012	0.056	-9999	-0.39	7	7
p38alpha-beta/MKP5	-0.012	0.057	-9999	-0.42	4	4
PGK/cGMP	-0.03	0.14	-9999	-0.64	43	43
PAK2	0	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.063	0.14	-9999	-0.4	128	128
CDC42	0	0	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
PAK3	-0.38	0.41	-9999	-0.82	421	421

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.003	0.039	-9999	-10000	0	0
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.047	0.14	-9999	-0.63	40	40
STXBP1	-0.004	0.054	-9999	-0.82	4	4
ACh/CHRNA1	-0.063	0.079	-9999	-0.27	9	9
RAB3GAP2/RIMS1/UNC13B	-0.039	0.12	-9999	-0.55	40	40
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	-0.067	0.18	-9999	-0.43	142	142
mol:ACh	0	0.032	-9999	-0.15	32	32
RAB3GAP2	0	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.038	0.097	-9999	-0.42	44	44
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.062	0.078	-9999	-0.27	9	9
UNC13B	0	0	-9999	-10000	0	0
CHRNA1	-0.1	0.13	-9999	-10000	0	0
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.06	0.13	-9999	-0.48	52	52
SNAP25	-0.017	0.071	-9999	-0.38	32	32
VAMP2	0	0	-9999	-10000	0	0
SYT1	-0.089	0.19	-9999	-0.37	220	220
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.008	0.046	-9999	-0.56	4	4
STX1A/SNAP25 fragment 1/VAMP2	-0.038	0.097	-9999	-0.42	44	44

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.031	0.072	-9999	-0.46	19	19
NF kappa B1 p50/RelA/I kappa B alpha	-0.018	0.058	-9999	-0.48	3	3
alphaV/beta3 Integrin/Osteopontin/Src	-0.045	0.073	-9999	-10000	0	0
AP1	-0.15	0.21	-9999	-0.78	26	26
ILK	-0.001	0.096	-9999	-0.49	19	19
bone resorption	-0.026	0.08	-9999	-0.66	6	6
PTK2B	0	0	-9999	-10000	0	0
PYK2/p130Cas	0.011	0.08	-9999	-0.44	19	19
ITGAV	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.008	0.067	-9999	-0.63	10	10
alphaV/beta3 Integrin/Osteopontin	-0.044	0.091	-9999	-0.55	19	19
MAP3K1	-0.001	0.097	-9999	-0.5	19	19
JUN	-0.008	0.081	-9999	-0.82	9	9
MAPK3	0.014	0.094	-9999	-0.46	19	19
MAPK1	0.014	0.094	-9999	-0.46	19	19
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0.01	0.1	-9999	-0.51	20	20
ITGB3	-0.018	0.12	-9999	-0.82	19	19
NFKBIA	0.027	0.09	-9999	-0.44	19	19
FOS	-0.26	0.38	-9999	-0.82	283	283
CD44	-0.001	0.016	-9999	-0.28	3	3
CHUK	0	0	-9999	-10000	0	0
PLAU	0.024	0.091	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.017	0.056	-9999	-0.46	3	3
BCAR1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.014	0.089	-9999	-0.62	19	19
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.003	0.097	-9999	-0.5	19	19
VAV3	0.003	0.1	-9999	-0.47	25	25
MAP3K14	0.001	0.098	-9999	-0.5	19	19
ROCK2	-0.009	0.086	-9999	-0.82	10	10
SPP1	-0.075	0.12	-9999	-0.27	254	254
RAC1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.031	0.074	-9999	-0.43	25	25
MMP2	-0.079	0.21	-9999	-0.69	26	26

×

Arf6 trafficking events

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
SLC2A4	-0.46	0.41	-10000	0	-0.82	513	513
CLTC	0.027	0.016	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.024	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	0.005	0.084	-10000	0	-0.56	20	20
CTNNB1	0	0	-10000	0	-10000	0	0
membrane fusion	-0.001	0.017	-10000	0	-10000	0	0
CTNND1	-0.005	0.023	-10000	0	-10000	0	0
DNM2	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.029	0.013	-10000	0	-10000	0	0
TSHR	-0.009	0.12	-10000	0	-0.56	41	41
INS	0.011	0.005	-10000	0	-10000	0	0
BIN1	-0.008	0.082	-10000	0	-0.77	10	10
mol:Choline	-0.001	0.017	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.009	0.036	-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	0.053	-10000	0	-0.51	10	10
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.016	0.054	-10000	0	-0.28	28	28
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0	0.009	-10000	0	-0.28	1	1
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	-0.004	0.033	-10000	0	-10000	0	0
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	0.009	0.035	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.018	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0.005	-10000	0	-10000	0	0
ACAP1	-0.001	0.018	-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	0.023	-10000	0	-10000	0	0
NME1	0.01	0.036	-10000	0	-10000	0	0
clathrin coat assembly	0.027	0.016	-10000	0	-10000	0	0
IL2RA	0.018	0.043	-10000	0	-0.33	11	11
VAMP3	0.018	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.24	0.21	-10000	0	-0.42	513	513
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	-0.002	0.028	-10000	0	-0.35	6	6
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0	0	-10000	0	-10000	0	0
PIP5K1C	0.03	0.013	-10000	0	-10000	0	0
SDC1	0.021	0.023	-10000	0	-0.36	1	1
ARF6/GDP	-0.007	0.032	-10000	0	-10000	0	0
EXOC7	0	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.009	0.036	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.001	0.017	-10000	0	-10000	0	0
endocytosis	0.006	0.052	0.5	10	-10000	0	10
SCAMP2	0	0	-10000	0	-10000	0	0
ADRB2	-0.084	0.21	-10000	0	-0.45	223	223
EXOC3	0	0	-10000	0	-10000	0	0
ASAP2	-0.001	0.027	-10000	0	-0.82	1	1
Dynamin 2/GDP	-0.006	0.026	-10000	0	-10000	0	0
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	-0.16	0.24	-10000	0	-0.45	367	367
RALA	0	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.008	0.031	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	-0.06	0.074	-9999	-0.42	6	6
EPHB2	-0.005	0.038	-9999	-10000	0	0
Syndecan-2/TACI	-0.017	0.079	-9999	-0.55	17	17
LAMA1	-0.096	0.26	-9999	-0.82	106	106
Syndecan-2/alpha2 ITGB1	-0.13	0.22	-9999	-0.49	239	239
HRAS	-0.001	0.013	-9999	-0.28	2	2
Syndecan-2/CASK	-0.003	0.033	-9999	-0.55	3	3
ITGA5	0	0	-9999	-10000	0	0
BAX	0.035	0.048	-9999	-0.65	2	2
EPB41	0	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.002	0.03	-9999	-0.5	3	3
LAMA3	-0.2	0.36	-9999	-0.82	227	227
EZR	-0.001	0.016	-9999	-0.28	3	3
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.1	0.28	-9999	-0.82	116	116
Syndecan-2/MMP2	-0.007	0.072	-9999	-0.73	8	8
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.013	0.09	-9999	-0.63	19	19
dendrite morphogenesis	-0.005	0.037	-9999	-0.54	3	3
Syndecan-2/GM-CSF	-0.005	0.038	-9999	-0.55	3	3
determination of left/right symmetry	0.016	0.039	-9999	-0.63	3	3
Syndecan-2/PKC delta	-0.003	0.033	-9999	-0.55	3	3
GNB2L1	0	0	-9999	-10000	0	0
MAPK3	0.022	0.038	-9999	-0.5	3	3
MAPK1	0.022	0.038	-9999	-0.5	3	3
Syndecan-2/RACK1	-0.002	0.028	-9999	-0.47	3	3
NF1	-0.001	0.027	-9999	-0.82	1	1
FGFR/FGF/Syndecan-2	0.016	0.039	-9999	-0.63	3	3
ITGA2	-0.017	0.12	-9999	-0.82	19	19
MAPK8	0.029	0.051	-9999	-0.58	6	6
Syndecan-2/alpha2/beta1 Integrin	-0.066	0.19	-9999	-0.54	112	112
Syndecan-2/Kininogen	-0.004	0.036	-9999	-0.55	3	3
ITGB1	0	0	-9999	-10000	0	0
SRC	-0.002	0.026	-9999	-0.44	3	3
Syndecan-2/CASK/Protein 4.1	-0.002	0.03	-9999	-0.5	3	3
extracellular matrix organization	-0.003	0.033	-9999	-0.54	3	3
actin cytoskeleton reorganization	-0.06	0.074	-9999	-0.42	6	6
Syndecan-2/Caveolin-2/Ras	-0.066	0.17	-9999	-0.51	116	116
Syndecan-2/Laminin alpha3	-0.14	0.24	-9999	-0.55	230	230
Syndecan-2/RasGAP	-0.002	0.027	-9999	-0.45	3	3
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
PRKCD	0	0.009	-9999	-0.28	1	1
Syndecan-2 dimer	-0.005	0.037	-9999	-0.55	3	3
GO:0007205	0	0.001	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.002	0.025	-9999	-0.43	3	3
RHOA	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
TNFRSF13B	-0.025	0.12	-9999	-0.82	14	14
RASA1	0	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.013	0.09	-9999	-0.63	19	19
Syndecan-2/Synbindin	-0.002	0.032	-9999	-0.55	3	3
TGFB1	0	0.009	-9999	-0.28	1	1
CASP3	0.029	0.032	-9999	-0.49	3	3
FN1	-0.12	0.14	-9999	-10000	0	0
Syndecan-2/IL8	-0.022	0.088	-9999	-0.55	21	21
SDC2	0.016	0.04	-9999	-0.63	3	3
KNG1	-0.004	0.032	-9999	-0.28	12	12
Syndecan-2/Neurofibromin	-0.003	0.037	-9999	-0.55	4	4
TRAPPC4	0	0	-9999	-10000	0	0
CSF2	-0.006	0.041	-9999	-10000	0	0
Syndecan-2/TGFB1	-0.003	0.033	-9999	-0.55	3	3
Syndecan-2/Syntenin/PI-4-5-P2	-0.002	0.03	-9999	-0.5	3	3
Syndecan-2/Ezrin	-0.002	0.03	-9999	-0.5	3	3
PRKACA	0.029	0.036	-9999	-0.5	4	4
angiogenesis	-0.022	0.088	-9999	-0.55	21	21
MMP2	-0.007	0.077	-9999	-0.82	8	8
IL8	-0.034	0.13	-9999	-0.41	77	77
calcineurin-NFAT signaling pathway	-0.017	0.079	-9999	-0.55	17	17

×

E-cadherin signaling events

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
E-cadherin/beta catenin-gamma catenin	-0.018	0.096	-9999	-0.55	29	29
E-cadherin/beta catenin	-0.019	0.11	-9999	-0.63	28	28
CTNNB1	0	0	-9999	-10000	0	0
JUP	-0.002	0.03	-9999	-0.82	1	1
CDH1	-0.025	0.14	-9999	-0.82	28	28

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.001	0.003	-9999	-10000	0	0
HDAC2	0.001	0.004	-9999	-10000	0	0
GNB1/GNG2	-0.008	0.071	-9999	-0.59	13	13
forebrain development	-0.027	0.2	-9999	-0.52	113	113
GNAO1	-0.034	0.14	-9999	-0.75	28	28
SMO/beta Arrestin2	-0.005	0.056	-9999	-0.64	7	7
SMO	-0.004	0.073	-9999	-0.76	8	8
ARRB2	0.002	0.005	-9999	-10000	0	0
GLI3/SPOP	-0.003	0.037	-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	-0.042	0.18	-9999	-0.83	47	47
XPO1	0.011	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.055	0.16	-9999	-0.52	68	68
SAP30	0	0.019	-9999	-10000	0	0
mol:GDP	-0.004	0.073	-9999	-0.76	8	8
MIM/GLI2A	0.001	0.029	-9999	-0.28	9	9
IFT88	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GLI2	0.041	0.033	-9999	-10000	0	0
GLI3	0.038	0.043	-9999	-0.31	12	12
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	0.072	-9999	-0.82	7	7
Gi family/GTP	-0.025	0.099	-9999	-0.32	81	81
SIN3B	0.001	0.004	-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	0.034	-9999	-0.41	4	4
FOXA2	-0.013	0.033	-9999	-10000	0	0
neural tube patterning	-0.027	0.2	-9999	-0.52	113	113
SPOP	0	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.002	0.022	-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	0.029	-9999	-0.28	9	9
embryonic limb morphogenesis	-0.027	0.2	-9999	-0.52	113	113
SUFU	-0.002	0.025	-9999	-0.29	3	3
LGALS3	-0.011	0.094	-9999	-0.82	12	12
catabolic process	-0.005	0.029	-9999	-10000	0	0
GLI3A/CBP	-0.026	0.097	-9999	-0.38	62	62
KIF3A	0	0	-9999	-10000	0	0
GLI1	-0.029	0.21	-9999	-0.54	113	113
RAB23	0	0	-9999	-10000	0	0
CSNK1A1	0	0	-9999	-10000	0	0
IFT172	-0.001	0.027	-9999	-0.82	1	1
RBBP7	-0.002	0.026	-9999	-0.28	8	8
Su(fu)/Galectin3	-0.009	0.066	-9999	-0.55	12	12
GNAZ	-0.007	0.077	-9999	-0.82	8	8
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	-0.028	0.096	-9999	-0.44	20	20
PTCH1	-0.069	0.35	-9999	-1.1	77	77
MIM/GLI1	-0.054	0.19	-9999	-0.59	65	65
CREBBP	-0.026	0.097	-9999	-0.38	62	62
Su(fu)/SIN3/HDAC complex	0.006	0.019	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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	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	0.006	-10000	0	-10000	0	0
CDKN1B	0.035	0.028	-10000	0	-0.45	3	3
CDKN1A	0.036	0.017	-10000	0	-0.45	1	1
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	-0.001	0.018	-10000	0	-10000	0	0
FOXO3	0.036	0.023	-10000	0	-0.45	2	2
AKT1	0	0.001	-10000	0	-10000	0	0
BAD	0	0	-10000	0	-10000	0	0
AKT3	-0.006	0.051	-10000	0	-0.45	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.037	0.002	-10000	0	-10000	0	0
AKT1/ASK1	-0.001	0.02	-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	0.02	0.42	2	-10000	0	2
TSC1	0.037	0.002	-10000	0	-10000	0	0
YWHAZ	-0.001	0.016	-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	0.019	-10000	0	-0.54	1	1
MAP3K5	-0.002	0.039	-10000	0	-0.82	2	2
MAPKAP1	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.039	0.023	-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	0.024	-10000	0	-0.42	3	3
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0	0.006	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-10000	0	0
AKT2/p21CIP1	0	0.014	-10000	0	-0.43	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	0.03	-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	-0.26	0.26	-10000	0	-0.5	513	513
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	-0.27	0.26	-10000	0	-0.5	513	513
GSK3A	0.037	0.002	-10000	0	-10000	0	0
FOXO1	0.032	0.045	-10000	0	-0.45	8	8
GSK3B	0.037	0.002	-10000	0	-10000	0	0
SFN	-0.016	0.1	-10000	0	-0.54	27	27
G1/S transition of mitotic cell cycle	0.043	0.002	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.041	0.034	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
KPNA1	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0.009	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0

×

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	0.022	-10000	0	-0.63	1	1
MAP4K4	-0.006	0.042	-10000	0	-0.71	1	1
BAG4	-0.004	0.04	-10000	0	-0.82	1	1
PKC zeta/ceramide	-0.024	0.049	-10000	0	-0.6	1	1
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.082	-10000	0	-0.82	8	8
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	0.046	0.2	1	-10000	0	1
SMPD1	0.024	0.037	-10000	0	-0.26	14	14
RB1	-0.024	0.051	0.2	1	-0.5	2	3
FADD/Caspase 8	-0.006	0.041	-10000	0	-0.67	1	1
MAP2K4	-0.015	0.046	-10000	0	-0.48	1	1
NSMAF	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.015	0.047	-10000	0	-0.47	1	1
EGF	-0.16	0.33	-10000	0	-0.82	183	183
mol:ceramide	-0.034	0.049	0.21	1	-10000	0	1
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	0.024	-10000	0	-0.63	1	1
ASAH1	-0.001	0.016	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.024	0.051	0.2	1	-0.49	2	3
cell proliferation	-0.096	0.16	-10000	0	-0.4	197	197
BID	0.022	0.037	-10000	0	-0.4	1	1
MAP3K1	-0.023	0.046	0.2	1	-10000	0	1
EIF2A	-0.006	0.042	-10000	0	-10000	0	0
TRADD	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
MAPK3	-0.003	0.045	-10000	0	-0.43	1	1
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.003	0.045	-10000	0	-0.43	1	1
Cathepsin D/ceramide	-0.029	0.05	-10000	0	-0.25	1	1
FADD	-0.007	0.045	-10000	0	-0.48	3	3
KSR1	-0.023	0.05	0.2	1	-0.33	3	4
MAPK8	-0.011	0.049	0.2	1	-0.31	5	6
PRKRA	-0.023	0.046	0.2	1	-10000	0	1
PDGFA	-0.001	0.027	-10000	0	-0.82	1	1
TRAF2	-0.001	0.013	-10000	0	-10000	0	0
IGF1	-0.18	0.34	-10000	0	-0.82	197	197
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.034	0.049	0.21	1	-10000	0	1
CTSD	-0.011	0.054	-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	-0.1	0.18	-10000	0	-0.43	197	197
PRKCD	0	0.009	-10000	0	-0.28	1	1
PRKCZ	-0.001	0.027	-10000	0	-0.82	1	1
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.021	0.024	-10000	0	-0.63	1	1
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.001	0.027	-10000	0	-0.82	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.007	0.046	-10000	0	-0.75	1	1
TNFR1A/BAG4/TNF-alpha	-0.013	0.073	-10000	0	-0.55	15	15
mol:Sphingosine-1-phosphate	0.021	0.022	-10000	0	-0.63	1	1
MAP2K1	-0.006	0.045	-10000	0	-0.44	1	1
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
CYCS	-0.008	0.044	0.19	21	-10000	0	21
TNFRSF1A	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.003	0.028	-10000	0	-0.63	1	1
EIF2AK2	-0.014	0.044	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.011	0.07	-10000	0	-0.55	14	14
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.003	0.023	-10000	0	-0.33	1	1
MAP2K2	-0.006	0.045	-10000	0	-0.44	1	1
SMPD3	0.024	0.044	-10000	0	-0.28	17	17
TNF	-0.018	0.11	-10000	0	-0.82	14	14
PKC zeta/PAR4	-0.001	0.03	-10000	0	-0.63	2	2
mol:PHOSPHOCHOLINE	0.047	0.12	0.28	182	-10000	0	182
NF kappa B1/RelA/I kappa B alpha	-0.001	0.022	-10000	0	-0.46	2	2
AIFM1	-0.008	0.044	0.19	21	-10000	0	21
BCL2	-0.027	0.15	-10000	0	-0.82	30	30

×

TRAIL signaling pathway

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.007	0.073	-10000	0	-0.82	7	7
positive regulation of NF-kappaB transcription factor activity	-0.065	0.19	-10000	0	-0.63	94	94
MAP2K4	0.042	0.037	-10000	0	-0.45	1	1
IKBKB	-0.001	0.013	-10000	0	-10000	0	0
TNFRSF10B	0	0	-10000	0	-10000	0	0
TNFRSF10A	-0.004	0.054	-10000	0	-0.82	4	4
SMPD1	-0.002	0.026	-10000	0	-0.29	7	7
IKBKG	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.079	0.24	-10000	0	-0.82	88	88
TRAIL/TRAILR2	-0.005	0.056	-10000	0	-0.63	7	7
TRAIL/TRAILR3	-0.009	0.072	-10000	0	-0.69	9	9
TRAIL/TRAILR1	-0.008	0.069	-10000	0	-0.63	11	11
TRAIL/TRAILR4	-0.066	0.19	-10000	0	-0.63	94	94
TRAIL/TRAILR1/DAP3/GTP	-0.006	0.055	-10000	0	-0.51	11	11
IKK complex	-0.002	0.019	-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	0.017	0.057	-10000	0	-0.63	7	7
MAP3K1	-0.003	0.03	-10000	0	-0.33	7	7
TRAILR4 (trimer)	-0.079	0.24	-10000	0	-0.82	88	88
TRADD	0	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	-0.004	0.054	-10000	0	-0.82	4	4
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.005	0.037	-10000	0	-0.34	11	11
CFLAR	0	0	-10000	0	-10000	0	0
MAPK1	0.017	0.057	-10000	0	-0.63	7	7
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.007	0.053	-10000	0	-0.48	11	11
mol:ceramide	-0.002	0.026	-10000	0	-0.29	7	7
FADD	-0.005	0.037	-10000	0	-0.28	16	16
MAPK8	0.046	0.045	-10000	0	-0.42	4	4
TRAF2	-0.001	0.013	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.005	0.054	-10000	0	-0.82	3	3
CHUK	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.009	0.063	-10000	0	-0.56	11	11
DAP3	0	0.009	-10000	0	-10000	0	0
CASP10	0.021	0.11	0.31	83	-0.52	10	93
JNK cascade	-0.065	0.19	-10000	0	-0.63	94	94
TRAIL (trimer)	-0.007	0.072	-10000	0	-0.82	7	7
TNFRSF10C	-0.005	0.054	-10000	0	-0.82	3	3
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.008	0.055	-10000	0	-0.48	11	11
TRAIL/TRAILR2/FADD	-0.007	0.051	-10000	0	-0.55	7	7
cell death	-0.002	0.025	-10000	0	-0.29	7	7
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.003	0.029	-10000	0	-0.33	7	7
TRAILR2 (trimer)	0	0	-10000	0	-10000	0	0
CASP8	0.001	0.014	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.005	0.042	-10000	0	-0.47	7	7

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.03	0.009	-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	0.016	0.088	-9999	-0.49	25	25
CCND1	0.015	0.043	-9999	-0.22	23	23
p38 gamma/SNTA1	-0.013	0.077	-9999	-0.48	21	21
MAP2K3	0	0.009	-9999	-0.28	1	1
PKN1	0	0	-9999	-10000	0	0
G2/M transition checkpoint	0.016	0.087	-9999	-0.49	25	25
MAP2K6	0.009	0.089	-9999	-0.52	25	25
MAPT	-0.017	0.14	-9999	-0.41	93	93
MAPK13	0.021	0.011	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	-0.002	0.03	-9999	-0.45	4	4

×

Caspase cascade in apoptosis

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.005	0.095	-10000	0	-0.47	30	30
ACTA1	-0.017	0.13	-10000	0	-0.66	29	29
NUMA1	0.005	0.095	-10000	0	-0.47	30	30
SPTAN1	-0.004	0.13	-10000	0	-0.64	27	27
LIMK1	-0.004	0.13	-10000	0	-0.64	27	27
BIRC3	-0.01	0.082	-10000	0	-0.82	8	8
BIRC2	0	0	-10000	0	-10000	0	0
BAX	-0.001	0.016	-10000	0	-10000	0	0
CASP10	-0.015	0.15	-10000	0	-0.69	31	31
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.005	0.095	-10000	0	-0.47	30	30
DIABLO	0	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.003	0.12	-10000	0	-0.63	27	27
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
GSN	-0.011	0.15	-10000	0	-0.65	36	36
MADD	0	0	-10000	0	-10000	0	0
TFAP2A	0.011	0.094	-10000	0	-0.7	15	15
BID	0.005	0.062	-10000	0	-0.3	30	30
MAP3K1	0.005	0.039	-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	-0.004	0.13	-10000	0	-0.64	27	27
CASP9	0	0.002	-10000	0	-10000	0	0
DNA repair	-0.002	0.03	0.19	1	-0.22	3	4
neuron apoptosis	0.021	0.014	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.003	0.12	-10000	0	-0.62	27	27
APAF1	0	0	-10000	0	-10000	0	0
CASP6	0.022	0.059	-10000	0	-0.43	4	4
TRAF2	-0.001	0.013	-10000	0	-10000	0	0
ICAD/CAD	0.004	0.12	-10000	0	-0.62	27	27
CASP7	-0.007	0.038	0.37	8	-10000	0	8
KRT18	0.015	0.017	-10000	0	-10000	0	0
apoptosis	0.009	0.11	-10000	0	-0.55	27	27
DFFA	-0.004	0.13	-10000	0	-0.64	27	27
DFFB	-0.004	0.13	-10000	0	-0.64	27	27
PARP1	0.002	0.03	0.22	3	-0.19	1	4
actin filament polymerization	-0.003	0.12	0.59	29	-10000	0	29
TNF	-0.018	0.11	-10000	0	-0.82	14	14
CYCS	0.008	0.05	-10000	0	-0.22	28	28
SATB1	0.018	0.099	-10000	0	-0.52	21	21
SLK	-0.004	0.13	-10000	0	-0.64	27	27
p15 BID/BAX	-0.013	0.049	-10000	0	-0.35	7	7
CASP2	0.042	0.044	-10000	0	-0.46	1	1
JNK cascade	-0.005	0.038	0.24	6	-10000	0	6
CASP3	-0.013	0.13	-10000	0	-0.66	30	30
LMNB2	0.039	0.041	-10000	0	-0.36	3	3
RIPK1	0	0	-10000	0	-10000	0	0
CASP4	-0.001	0.027	-10000	0	-0.82	1	1
Mammalian IAPs/DIABLO	-0.006	0.048	-10000	0	-0.5	8	8
negative regulation of DNA binding	0.011	0.093	-10000	0	-0.69	15	15
stress fiber formation	-0.003	0.12	-10000	0	-0.63	27	27
GZMB	-0.028	0.16	-10000	0	-0.67	38	38
CASP1	-0.002	0.033	-10000	0	-0.45	5	5
LMNB1	0.044	0.041	-10000	0	-0.36	3	3
APP	0.021	0.014	-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	0.1	-10000	0	-0.53	27	27
LMNA	0.039	0.041	-10000	0	-0.36	3	3
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.006	0.039	-10000	0	-0.5	1	1
LRDD	-0.001	0.013	-10000	0	-10000	0	0
SREBF1	-0.006	0.13	-10000	0	-0.65	27	27
APAF-1/Caspase 9	-0.004	0.019	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.006	0.093	-10000	0	-0.46	30	30
CFL2	0.003	0.12	-10000	0	-0.61	29	29
GAS2	-0.052	0.19	-10000	0	-0.54	110	110
positive regulation of apoptosis	0.045	0.041	-10000	0	-0.35	3	3
PRF1	-0.019	0.12	-10000	0	-0.82	18	18

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0	0	-9999	-10000	0	0
PLK4	-0.012	0.057	-9999	-0.28	40	40
regulation of centriole replication	0.013	0.04	-9999	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0	0.009	-10000	0	-10000	0	0
ANTXR2	-0.008	0.081	-10000	0	-0.82	9	9
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.001	0.01	-10000	0	-0.1	9	9
monocyte activation	0.004	0.071	-10000	0	-0.46	21	21
MAP2K2	0	0.004	-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	0.075	-10000	0	-0.5	21	21
CYAA	-0.005	0.048	-10000	0	-0.48	9	9
MAP2K4	-0.001	0.018	-10000	0	-0.5	1	1
IL1B	0.008	0.065	-10000	0	-0.36	23	23
Channel	-0.005	0.051	-10000	0	-0.52	9	9
NLRP1	-0.007	0.056	-10000	0	-0.51	11	11
CALM1	0	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.001	0.012	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.001	0.01	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	-0.14	0.22	-10000	0	-0.5	253	253
PA/Cellular Receptors	-0.006	0.055	-10000	0	-0.56	9	9
apoptosis	-0.001	0.01	-10000	0	-0.1	9	9
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.005	0.048	-10000	0	-0.48	9	9
macrophage activation	0.02	0.009	-10000	0	-10000	0	0
TNF	-0.018	0.11	-10000	0	-0.82	14	14
VCAM1	-0.01	0.069	-10000	0	-0.46	21	21
platelet activation	-0.001	0.012	-10000	0	-10000	0	0
MAPKKK cascade	-0.013	0.022	0.24	2	-10000	0	2
IL18	0.011	0.034	-10000	0	-0.22	11	11
negative regulation of macrophage activation	-0.001	0.01	-10000	0	-0.1	9	9
LEF	-0.001	0.01	-10000	0	-0.1	9	9
CASP1	-0.004	0.028	-10000	0	-0.24	11	11
mol:cAMP	-0.001	0.012	-10000	0	-10000	0	0
necrosis	-0.001	0.01	-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	0.048	-10000	0	-0.49	9	9
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.026	0.029	-9999	-10000	0	0
BIRC5	-0.2	0.12	-9999	-10000	0	0
NFKBIA	-0.024	0.031	-9999	-10000	0	0
CPEB1	-0.16	0.32	-9999	-0.82	175	175
AKT1	-0.024	0.031	-9999	-10000	0	0
NDEL1	0	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.023	0.026	-9999	-10000	0	0
NDEL1/TACC3	-0.038	0.057	-9999	-10000	0	0
GADD45A	0	0	-9999	-10000	0	0
GSK3B	0.001	0.002	-9999	-10000	0	0
PAK1/Aurora A	-0.029	0.037	-9999	-10000	0	0
MDM2	-0.001	0.018	-9999	-10000	0	0
JUB	-0.004	0.054	-9999	-0.82	4	4
TPX2	-0.11	0.095	-9999	-10000	0	0
TP53	-0.011	0.015	-9999	-10000	0	0
DLG7	-0.03	0.034	-9999	-10000	0	0
AURKAIP1	-0.002	0.021	-9999	-0.28	5	5
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	0.061	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.023	0.026	-9999	-10000	0	0
AURKA	-0.038	0.043	-9999	-10000	0	0
AURKB	-0.003	0.008	-9999	-10000	0	0
CDC25B	-0.017	0.024	-9999	-10000	0	0
G2/M transition checkpoint	-0.025	0.041	-9999	-0.52	4	4
mRNA polyadenylation	-0.12	0.21	-9999	-0.55	174	174
Aurora A/CPEB	-0.12	0.21	-9999	-0.55	174	174
Aurora A/TACC1/TRAP/chTOG	-0.027	0.08	-9999	-0.5	25	25
BRCA1	-0.001	0.013	-9999	-10000	0	0
centrosome duplication	-0.029	0.037	-9999	-10000	0	0
regulation of centrosome cycle	-0.038	0.056	-9999	-10000	0	0
spindle assembly	-0.027	0.079	-9999	-0.49	25	25
TDRD7	0	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.099	0.065	-9999	-10000	0	0
CENPA	0.001	0.01	-9999	-10000	0	0
Aurora A/PP2A	-0.026	0.029	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.006	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	-0.025	0.042	-9999	-0.52	4	4
mitotic prometaphase	-0.014	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.038	0.043	-9999	-10000	0	0
TACC1	-0.023	0.14	-9999	-0.82	25	25
TACC3	-0.043	0.1	-9999	-0.28	141	141
Aurora A/Antizyme1	-0.02	0.021	-9999	-10000	0	0
Aurora A/RasGAP	-0.026	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	0.002	-9999	-10000	0	0
GIT1	-0.001	0.018	-9999	-0.28	4	4
GIT1/beta-PIX/PAK1	-0.004	0.021	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.11	0.094	-9999	-10000	0	0
PPP2R5D	0	0	-9999	-10000	0	0
Aurora A/TPX2	-0.11	0.082	-9999	-10000	0	0
PAK1	-0.006	0.041	-9999	-10000	0	0
CKAP5	0	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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
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	0.038	0.035	-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	0.045	0.24	4	-0.34	8	12
RAR alpha/9cRA/Cyclin H	-0.01	0.059	-10000	0	-0.38	21	21
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.035	0.046	-10000	0	-0.33	10	10
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	-0.009	0.053	-10000	0	-0.57	4	4
NCOR2	0	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0	0	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	0.006	0.12	-10000	0	-0.58	23	23
NCOA2	-0.015	0.11	-10000	0	-0.82	17	17
NCOA3	0	0.009	-10000	0	-10000	0	0
NCOA1	-0.001	0.027	-10000	0	-0.82	1	1
VDR/VDR/DNA	0	0	-10000	0	-10000	0	0
RARG	0.007	0.006	-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	-0.003	0.047	-10000	0	-0.82	3	3
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.042	0.1	-10000	0	-0.63	21	21
RARA	0.016	0.055	-10000	0	-0.31	24	24
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.03	0.058	-10000	0	-0.28	27	27
PRKCA	-0.006	0.13	-10000	0	-0.78	23	23
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.005	0.12	-10000	0	-0.59	25	25
RXRG	-0.11	0.22	-10000	0	-0.45	249	249
RXRA	0.024	0.059	-10000	0	-0.33	24	24
RXRB	0.012	0.072	-10000	0	-0.45	21	21
VDR/Vit D3/DNA	0	0	-10000	0	-10000	0	0
RBP1	-0.022	0.096	-10000	0	-0.34	59	59
CRBP1/9-cic-RA	-0.016	0.07	-10000	0	-0.64	7	7
RARB	0.003	0.087	-10000	0	-0.82	10	10
PRKCG	-0.001	0.055	-10000	0	-10000	0	0
MNAT1	0	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.027	0.11	-10000	0	-0.62	23	23
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.013	0.1	-10000	0	-0.49	24	24
proteasomal ubiquitin-dependent protein catabolic process	0.038	0.049	-10000	0	-0.43	2	2
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.005	0.12	-10000	0	-0.59	25	25
positive regulation of DNA binding	-0.009	0.056	-10000	0	-0.36	21	21
NRIP1	-0.003	0.12	-10000	0	-0.59	22	22
RXRs/RARs	-0.012	0.12	-10000	0	-0.57	26	26
RXRs/RXRs/DNA/9cRA	-0.046	0.11	-10000	0	-0.66	21	21
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	0.03	-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

×

S1P4 pathway

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
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.034	0.14	-9999	-0.82	24	24
CDC42/GTP	-0.026	0.08	-9999	-0.32	35	35
PLCG1	-0.027	0.083	-9999	-0.52	4	4
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	0.079	-9999	-0.31	35	35
S1PR5	-0.008	0.059	-9999	-0.36	19	19
S1PR4	-0.014	0.082	-9999	-0.82	6	6
MAPK3	-0.027	0.083	-9999	-0.52	4	4
MAPK1	-0.027	0.083	-9999	-0.33	35	35
S1P/S1P5/Gi	-0.028	0.092	-9999	-0.38	34	34
GNAI1	-0.042	0.18	-9999	-0.82	47	47
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.004	0.037	-9999	-0.56	3	3
RHOA	-0.006	0.042	-9999	-0.47	6	6
S1P/S1P4/Gi	-0.03	0.09	-9999	-0.36	35	35
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.007	0.077	-9999	-0.82	8	8
S1P/S1P4/G12/G13	-0.007	0.046	-9999	-0.51	6	6
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.024	0.08	0.52	6	-10000	0	6
GNAI2	0	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.004	0.037	-10000	0	-0.56	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.034	0.14	-10000	0	-0.82	24	24
RhoA/GTP	-0.025	0.082	-10000	0	-0.53	6	6
negative regulation of cAMP metabolic process	-0.028	0.091	-10000	0	-0.37	34	34
GNAZ	-0.007	0.077	-10000	0	-0.82	8	8
GNAI3	0	0	-10000	0	-10000	0	0
GNA12	0	0	-10000	0	-10000	0	0
S1PR5	-0.008	0.059	-10000	0	-0.36	19	19
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.028	0.092	-10000	0	-0.38	34	34
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
GNAI1	-0.042	0.18	-10000	0	-0.82	47	47

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.019	0.1	-9999	-0.6	28	28
KLHL20	-0.009	0.034	-9999	-0.25	3	3
CYFIP2	-0.01	0.061	-9999	-0.32	29	29
Rac1/GDP	0.047	0.073	-9999	-0.45	2	2
ENAH	-0.019	0.1	-9999	-0.59	28	28
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	-0.01	0.052	-9999	-0.51	1	1
ABI1/Sra1/Nap1	-0.006	0.024	-9999	-0.17	1	1
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.019	0.09	-9999	-0.5	30	30
RAPGEF1	0.037	0.095	-9999	-0.5	28	28
CTNND1	0	0.009	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.019	0.11	-9999	-0.62	28	28
CRK	0.028	0.1	-9999	-0.55	28	28
E-cadherin/gamma catenin/alpha catenin	-0.018	0.096	-9999	-0.55	29	29
alphaE/beta7 Integrin	-0.005	0.039	-9999	-0.63	2	2
IQGAP1	0	0	-9999	-10000	0	0
NCKAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.003	0.037	-9999	-0.51	5	5
DLG1	-0.019	0.1	-9999	-0.59	28	28
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.007	0.038	-9999	-0.34	1	1
MLLT4	-0.005	0.061	-9999	-0.82	5	5
ARF6/GTP/NME1/Tiam1	-0.007	0.027	-9999	-10000	0	0
PI3K	-0.009	0.049	-9999	-0.47	1	1
ARF6	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.02	0.11	-9999	-0.63	29	29
TIAM1	-0.001	0.018	-9999	-10000	0	0
E-cadherin(dimer)/Ca2+	-0.015	0.082	-9999	-0.47	28	28
AKT1	-0.005	0.027	-9999	-0.24	1	1
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
CDH1	-0.025	0.14	-9999	-0.82	28	28
RhoA/GDP	0.047	0.073	-9999	-0.44	2	2
actin cytoskeleton organization	-0.006	0.025	-9999	-0.18	3	3
CDC42/GDP	0.047	0.073	-9999	-0.36	28	28
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.011	0.061	-9999	-0.35	29	29
ITGB7	-0.008	0.057	-9999	-0.33	23	23
RAC1	0	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.015	0.086	-9999	-0.5	28	28
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.015	0.083	-9999	-0.48	28	28
mol:GDP	0.044	0.085	-9999	-0.42	28	28
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	-0.002	0.03	-9999	-0.82	1	1
p120 catenin/RhoA/GDP	-0.011	0.063	-9999	-0.55	1	1
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	0.028	-9999	-0.21	6	6
NME1	-0.014	0.062	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.019	0.1	-9999	-0.59	29	29
regulation of cell-cell adhesion	-0.009	0.046	-9999	-0.43	1	1
WASF2	-0.003	0.012	-9999	-10000	0	0
Rap1/GTP	-0.011	0.06	-9999	-0.61	1	1
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.085	-9999	-0.47	31	31
CCND1	-0.009	0.035	-9999	-0.26	6	6
VAV2	0.032	0.1	-9999	-0.52	28	28
RAP1/GDP	-0.011	0.061	-9999	-0.57	1	1
adherens junction assembly	-0.018	0.1	-9999	-0.57	29	29
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	-0.017	0.081	-9999	-0.44	31	31
E-cadherin/beta catenin	-0.016	0.087	-9999	-0.51	28	28
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.019	0.1	-9999	-0.59	28	28
PIK3CA	0	0.009	-9999	-10000	0	0
Rac1/GTP	-0.011	0.055	-9999	-0.42	3	3
E-cadherin/beta catenin/alpha catenin	-0.017	0.094	-9999	-0.55	28	28
ITGAE	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.02	0.11	-9999	-0.64	28	28

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.002	0.039	-9999	-0.82	2	2
mol:S1P	0.001	0.003	-9999	-10000	0	0
S1P1/S1P/Gi	-0.029	0.097	-9999	-0.34	76	76
GNAO1	-0.023	0.14	-9999	-0.8	25	25
S1P/S1P3/G12/G13	-0.001	0.012	-9999	-10000	0	0
AKT1	-0.01	0.045	-9999	-0.68	2	2
AKT3	0.017	0.17	-9999	-1.4	12	12
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.002	0.038	-9999	-0.82	2	2
GNAI2	0.011	0.003	-9999	-10000	0	0
GNAI3	0.01	0.004	-9999	-10000	0	0
GNAI1	-0.032	0.18	-9999	-0.83	47	47
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.009	0.029	-9999	-0.32	1	1
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.01	0.11	-9999	-0.39	35	35
MAPK3	0.018	0.1	-9999	-0.52	11	11
MAPK1	0.018	0.1	-9999	-0.38	31	31
JAK2	0.02	0.1	-9999	-0.46	17	17
CXCR4	0.014	0.1	-9999	-0.49	16	16
FLT1	0.012	0.028	-9999	-0.84	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.017	0.1	-9999	-0.52	11	11
S1P/S1P3/Gi	0.009	0.11	-9999	-0.4	35	35
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.024	0.085	-9999	-0.51	11	11
VEGFA	0.01	0.029	-9999	-0.28	9	9
S1P/S1P2/Gi	-0.028	0.09	-9999	-0.38	34	34
VEGFR1 homodimer/VEGFA homodimer	0.021	0.03	-9999	-0.66	1	1
RHOA	0	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.006	0.041	-9999	-0.34	13	13
GNAQ	-0.002	0.039	-9999	-0.82	2	2
GNAZ	0.003	0.078	-9999	-0.83	8	8
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.014	0.087	-9999	-0.42	30	30
GNA15	-0.003	0.035	-9999	-0.36	7	7
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	-0.002	0.039	-9999	-0.82	2	2
Rac1/GTP	-0.024	0.085	-9999	-0.51	11	11

×

IL1-mediated signaling events

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0.008	-10000	0	-10000	0	0
PRKCZ	-0.001	0.027	-10000	0	-0.82	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	-0.006	0.037	-10000	0	-0.43	3	3
IRAK/TOLLIP	-0.001	0.009	-10000	0	-10000	0	0
IKBKB	-0.001	0.013	-10000	0	-10000	0	0
IKBKG	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.032	0.12	-10000	0	-0.62	36	36
IL1A	-0.005	0.038	-10000	0	-0.28	17	17
IL1B	0.01	0.096	-10000	0	-0.75	13	13
IRAK/TRAF6/p62/Atypical PKCs	-0.001	0.016	-10000	0	-0.42	1	1
IL1R2	-0.038	0.16	-10000	0	-0.59	59	59
IL1R1	-0.011	0.094	-10000	0	-0.82	12	12
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0	0.058	0.24	25	-0.33	11	36
TOLLIP	0	0.009	-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	0.004	-10000	0	-10000	0	0
JUN	0.031	0.083	-10000	0	-0.4	32	32
MAP3K7	0	0.009	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.014	0.09	-10000	0	-0.51	25	25
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.009	0.059	-10000	0	-0.5	12	12
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.008	0.054	-10000	0	-0.47	12	12
IL1 beta fragment/IL1R1/IL1RAP	-0.016	0.099	-10000	0	-0.58	24	24
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	0.028	0.073	-10000	0	-0.41	24	24
IRAK1	0.021	0.012	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.017	0.084	-10000	0	-0.63	14	14
IRAK4	0	0	-10000	0	-10000	0	0
PRKCI	0	0.009	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
PI3K	-0.001	0.022	-10000	0	-0.63	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.009	0.053	-10000	0	-0.36	14	14
CHUK	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.016	0.099	-10000	0	-0.58	24	24
IL1 beta/IL1R2	-0.034	0.13	-10000	0	-0.58	47	47
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.007	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.013	0.08	-10000	0	-0.9	3	3
IRAK3	-0.026	0.14	-10000	0	-0.81	29	29
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.014	0.089	-10000	0	-0.52	24	24
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.005	0.038	-10000	0	-0.33	12	12
IL1 alpha/IL1R1/IL1RAP	-0.01	0.065	-10000	0	-0.55	12	12
RELA	0	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	-0.001	0.013	-10000	0	-10000	0	0
MYD88	0	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	-0.001	0.007	-10000	0	-10000	0	0
IL1RAP	0	0	-10000	0	-10000	0	0
UBE2N	0	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.011	0.071	-10000	0	-0.8	3	3
CASP1	-0.004	0.054	-10000	0	-0.82	4	4
IL1RN/IL1R2	-0.037	0.13	-10000	0	-0.6	40	40
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.015	0.093	-10000	0	-0.54	24	24
TMEM189-UBE2V1	-0.001	0.013	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.005	0.043	-10000	0	-0.38	12	12
PIK3CA	0	0.009	-10000	0	-10000	0	0
IL1RN	-0.013	0.066	-10000	0	-0.82	2	2
TRAF6/TAK1/TAB1/TAB2	0	0.006	-10000	0	-10000	0	0
MAP2K6	-0.011	0.066	-10000	0	-0.44	21	21

×

BARD1 signaling events

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
BARD1/CSTF1	-0.005	0.052	-10000	0	-0.63	6	6
ATM	0	0	-10000	0	-10000	0	0
UBE2D3	0	0	-10000	0	-10000	0	0
PRKDC	-0.001	0.018	-10000	0	-10000	0	0
ATR	0	0	-10000	0	-10000	0	0
UBE2L3	0	0	-10000	0	-10000	0	0
FANCD2	-0.001	0.007	-10000	0	-10000	0	0
protein ubiquitination	-0.022	0.055	-10000	0	-0.5	6	6
XRCC5	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0	0	-10000	0	-10000	0	0
DNA-PK	-0.001	0.009	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.002	0.01	-10000	0	-10000	0	0
FANCF	0	0.009	-10000	0	-0.28	1	1
BRCA1	-0.001	0.013	-10000	0	-10000	0	0
CCNE1	-0.054	0.11	-10000	0	-0.28	176	176
CDK2/Cyclin E1	-0.034	0.069	-10000	0	-10000	0	0
FANCG	0	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.005	0.052	-10000	0	-0.63	6	6
FANCE	0	0	-10000	0	-10000	0	0
FANCC	0	0	-10000	0	-10000	0	0
NBN	0	0	-10000	0	-10000	0	0
FANCA	-0.052	0.11	-10000	0	-0.28	171	171
DNA repair	0.012	0.082	-10000	0	-0.49	3	3
BRCA1/BARD1/ubiquitin	-0.005	0.052	-10000	0	-0.63	6	6
BARD1/DNA-PK	-0.004	0.041	-10000	0	-0.5	6	6
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.005	0.052	0.63	6	-10000	0	6
BRCA1/BARD1/CTIP/M/R/N Complex	-0.002	0.026	-10000	0	-0.32	6	6
BRCA1/BACH1/BARD1/TopBP1	-0.004	0.045	-10000	0	-0.55	6	6
BRCA1/BARD1/P53	-0.004	0.041	-10000	0	-0.5	6	6
BARD1/CSTF1/BRCA1	-0.004	0.045	-10000	0	-0.55	6	6
BRCA1/BACH1	-0.001	0.013	-10000	0	-10000	0	0
BARD1	-0.006	0.067	-10000	0	-0.75	7	7
PCNA	-0.001	0.016	-10000	0	-0.28	3	3
BRCA1/BARD1/UbcH5C	-0.004	0.045	-10000	0	-0.55	6	6
BRCA1/BARD1/UbcH7	-0.004	0.045	-10000	0	-0.55	6	6
BRCA1/BARD1/RAD51/PCNA	-0.048	0.07	-10000	0	-0.56	6	6
BARD1/DNA-PK/P53	-0.004	0.038	-10000	0	-0.47	6	6
BRCA1/BARD1/Ubiquitin	-0.005	0.052	-10000	0	-0.63	6	6
BRCA1/BARD1/CTIP	-0.004	0.041	-10000	0	-0.5	6	6
FA complex	-0.004	0.009	-10000	0	-10000	0	0
BARD1/EWS	-0.004	0.052	-10000	0	-0.63	6	6
RBBP8	0.022	0.007	-10000	0	-10000	0	0
TP53	0	0	-10000	0	-10000	0	0
TOPBP1	0	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.004	0.04	0.5	6	-10000	0	6
BRCA1/BARD1	-0.022	0.055	-10000	0	-0.51	6	6
CSTF1	0	0.009	-10000	0	-0.28	1	1
BARD1/EWS-Fli1	-0.004	0.052	-10000	0	-0.64	6	6
CDK2	0	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.11	0.14	-10000	0	-10000	0	0
RAD50	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.005	0.052	-10000	0	-0.63	6	6
EWSR1	0	0	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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
LAT/GRAP2/SLP76/HPK1	-0.016	0.083	-9999	-0.54	19	19
MAP4K1	-0.012	0.064	-9999	-0.82	2	2
MAP3K8	-0.005	0.062	-9999	-0.82	5	5
PRKCB	-0.019	0.11	-9999	-0.82	16	16
DBNL	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
MAP3K1	-0.006	0.045	-9999	-0.57	2	2
JUN	0.018	0.11	-9999	-0.57	28	28
MAP3K7	-0.006	0.045	-9999	-0.57	2	2
GRAP2	-0.014	0.1	-9999	-0.82	14	14
CRK	0	0	-9999	-10000	0	0
MAP2K4	0.044	0.056	-9999	-0.51	4	4
LAT	-0.005	0.048	-9999	-0.82	2	2
LCP2	0	0.009	-9999	-0.28	1	1
MAPK8	0.015	0.1	-9999	-0.67	19	19
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.007	0.049	-9999	-0.37	14	14
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.014	0.078	-9999	-0.52	17	17

×

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	0.05	-10000	0	-0.48	2	2
UGCG	-0.003	0.051	-10000	0	-0.73	4	4
AKT1/mTOR/p70S6K/Hsp90/TERT	0.057	0.084	-10000	0	-0.38	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.021	0.053	-10000	0	-0.72	4	4
mol:DAG	0	0.002	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.023	0.081	-10000	0	-0.36	32	32
FRAP1	0.056	0.12	-10000	0	-0.38	53	53
FOXO3	0.064	0.097	-10000	0	-0.38	26	26
AKT1	0.059	0.099	-10000	0	-0.41	24	24
GAB2	-0.002	0.026	-10000	0	-10000	0	0
SMPD1	-0.001	0.012	-10000	0	-10000	0	0
SGMS1	-0.001	0.012	-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	0.021	0.02	-10000	0	-0.55	1	1
CALM1	0	0	-10000	0	-10000	0	0
cell proliferation	0.038	0.062	-10000	0	-0.27	26	26
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	-0.001	0.022	-10000	0	-0.63	1	1
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	0.037	-10000	0	-10000	0	0
PIK3R1	0.012	0.028	-10000	0	-0.82	1	1
JAK1	0.013	0.004	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
MYC	0.049	0.18	-10000	0	-0.99	22	22
MYB	0.014	0.17	-10000	0	-1.3	15	15
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.057	0.079	-10000	0	-0.59	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	0.077	-10000	0	-0.57	4	4
Rac1/GDP	-0.001	0.017	-10000	0	-0.5	1	1
T cell proliferation	0.062	0.074	-10000	0	-0.49	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	15	15
PRKCZ	0.062	0.076	-10000	0	-0.52	5	5
NF kappa B1 p50/RelA	-0.022	0.079	-10000	0	-0.44	8	8
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.016	0.053	-10000	0	-0.54	2	2
HSP90AA1	0	0.009	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
IL2RA	-0.028	0.11	-10000	0	-0.36	72	72
IL2RB	0.001	0.058	-10000	0	-0.28	38	38
TERT	-0.038	0.096	-10000	0	-10000	0	0
E2F1	0.025	0.06	-10000	0	-0.44	15	15
SOS1	0	0	-10000	0	-10000	0	0
RPS6	0	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.004	0.03	15	-10000	0	15
PTPN11	0	0	-10000	0	-10000	0	0
IL2RG	-0.003	0.083	-10000	0	-0.82	5	5
actin cytoskeleton organization	0.062	0.074	-10000	0	-0.49	5	5
GRB2	0	0.009	-10000	0	-10000	0	0
IL2	0.006	0.027	-10000	0	-0.28	8	8
PIK3CA	0.013	0.01	-10000	0	-10000	0	0
Rac1/GTP	0.03	0.019	-10000	0	-0.48	1	1
LCK	-0.006	0.1	-10000	0	-0.43	39	39
BCL2	0.042	0.19	-10000	0	-0.9	32	32

×

Signaling events mediated by HDAC Class II

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	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	-0.5	7	7
HDAC3	0	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.014	-10000	0	-0.42	1	1
GATA1/HDAC4	-0.003	0.028	-10000	0	-0.63	1	1
GATA1/HDAC5	-0.002	0.019	-10000	0	-10000	0	0
GATA2/HDAC5	-0.018	0.1	-10000	0	-0.63	23	23
HDAC5/BCL6/BCoR	-0.002	0.036	-10000	0	-0.55	4	4
HDAC9	-0.009	0.074	-10000	0	-0.82	6	6
Glucocorticoid receptor/Hsp90/HDAC6	-0.006	0.057	-10000	0	-0.55	10	10
HDAC4/ANKRA2	-0.001	0.021	-10000	0	-0.63	1	1
HDAC5/YWHAB	0	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0	-10000	0	-10000	0	0
GATA2	-0.024	0.13	-10000	0	-0.82	23	23
HDAC4/RFXANK	-0.001	0.022	-10000	0	-0.63	1	1
BCOR	-0.001	0.027	-10000	0	-0.82	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	0.055	-10000	0	-0.63	7	7
Histones	-0.002	0.023	-10000	0	-10000	0	0
ADRBK1	0	0	-10000	0	-10000	0	0
HDAC4	-0.001	0.027	-10000	0	-0.82	1	1
XPO1	0	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0	0	-10000	0	-10000	0	0
HDAC4/Ubc9	-0.001	0.021	-10000	0	-0.63	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	0.008	-10000	0	-10000	0	0
CAMK4	-0.01	0.053	-10000	0	-0.28	34	34
Tubulin/HDAC6	0	0.006	-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	-0.28	11	11
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
NR3C1	-0.009	0.086	-10000	0	-0.82	10	10
SUMO1/HDAC4	-0.001	0.015	-10000	0	-0.46	1	1
SRF	0	0	-10000	0	-10000	0	0
HDAC4/YWHAB	-0.001	0.021	-10000	0	-0.63	1	1
Tubulin	0	0.008	-10000	0	-10000	0	0
HDAC4/14-3-3 E	-0.001	0.021	-10000	0	-0.63	1	1
GNB1	0	0	-10000	0	-10000	0	0
RANGAP1	0	0	-10000	0	-10000	0	0
BCL6/BCoR	-0.003	0.042	-10000	0	-0.63	4	4
HDAC4/HDAC3/SMRT (N-CoR2)	-0.001	0.018	-10000	0	-0.55	1	1
HDAC4/SRF	-0.006	0.031	-10000	0	-0.55	1	1
HDAC4/ER alpha	-0.11	0.22	-10000	0	-0.63	132	132
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.002	0.023	-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	-0.003	0.047	-10000	0	-0.82	3	3
HDAC4/CaMK II delta B	-0.001	0.027	-10000	0	-0.82	1	1
Hsp90/HDAC6	0	0.006	-10000	0	-10000	0	0
ESR1	-0.15	0.29	-10000	0	-0.57	248	248
HDAC6/HDAC11	0	0.008	-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	0.027	-10000	0	-0.82	1	1
RAN	0	0	-10000	0	-10000	0	0
HDAC4/MEF2C	-0.001	0.022	-10000	0	-0.47	2	2
GNG2	-0.006	0.072	-10000	0	-0.82	7	7
NCOR2	0	0	-10000	0	-10000	0	0
TUBB2A	-0.001	0.013	-10000	0	-0.28	2	2
HDAC11	-0.001	0.013	-10000	0	-0.28	2	2
HSP90AA1	0	0.009	-10000	0	-10000	0	0
RANBP2	0	0	-10000	0	-10000	0	0
ANKRA2	0	0	-10000	0	-10000	0	0
RFXANK	-0.001	0.013	-10000	0	-0.28	2	2
nuclear import	0	0.015	0.45	1	-10000	0	1

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0	0	-9999	-10000	0	0
SPHK1	-0.005	0.05	-9999	-0.36	14	14
GNAI2	0	0	-9999	-10000	0	0
mol:S1P	-0.001	0.018	-9999	-0.37	2	2
GNAO1	-0.034	0.14	-9999	-0.82	24	24
mol:Sphinganine-1-P	0.018	0.038	-9999	-0.63	2	2
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.001	0.012	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	-0.003	0.028	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.001	0.015	-9999	-0.32	2	2
S1PR5	-0.008	0.059	-9999	-0.36	19	19
S1PR4	-0.014	0.082	-9999	-0.82	6	6
GNAI1	-0.042	0.18	-9999	-0.82	47	47
S1P/S1P5/G12	-0.004	0.034	-9999	-0.49	3	3
S1P/S1P3/Gq	-0.004	0.036	-9999	-0.32	3	3
S1P/S1P4/Gi	-0.028	0.087	-9999	-0.35	37	37
GNAQ	-0.002	0.039	-9999	-0.82	2	2
GNAZ	-0.007	0.077	-9999	-0.82	8	8
GNA14	-0.014	0.087	-9999	-0.42	30	30
GNA15	-0.003	0.035	-9999	-0.36	7	7
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	-0.002	0.039	-9999	-0.82	2	2
ABCC1	0	0	-9999	-10000	0	0

×

mTOR signaling pathway

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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0	0	-10000	0	-10000	0	0
mol:PIP3	-0.014	0.07	0.33	1	-0.35	36	37
FRAP1	0.012	0.016	-10000	0	-10000	0	0
AKT1	-0.012	0.059	0.24	1	-0.29	36	37
INSR	0	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0.005	-10000	0	-10000	0	0
mol:GTP	-0.009	0.045	-10000	0	-0.37	2	2
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.003	0.013	-10000	0	-10000	0	0
TSC2	0	0.001	-10000	0	-10000	0	0
RHEB/GDP	-0.008	0.038	-10000	0	-0.33	2	2
TSC1	0	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.017	0.083	-10000	0	-0.43	36	36
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.003	0.016	-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	0.036	-10000	0	-0.27	2	2
MAP3K5	0.009	0.022	-10000	0	-0.45	2	2
PIK3R1	-0.001	0.027	-10000	0	-0.82	1	1
apoptosis	0.009	0.022	-10000	0	-0.45	2	2
mol:LY294002	0	0	0.001	1	-0.002	36	37
EIF4B	0.027	0.033	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.005	0.023	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	-0.001	0.004	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.016	0.075	-10000	0	-0.38	37	37
mTOR/RHEB/GTP/Raptor/GBL	0.027	0.024	0.18	1	-0.19	2	3
FKBP1A	0	0.009	-10000	0	-0.28	1	1
RHEB/GTP	-0.008	0.037	-10000	0	-0.33	2	2
mol:Amino Acids	0	0	0.001	1	-0.002	36	37
FKBP12/Rapamycin	0	0.006	-10000	0	-10000	0	0
PDPK1	-0.012	0.062	0.26	1	-0.32	36	37
EIF4E	0	0	-10000	0	-10000	0	0
ASK1/PP5C	-0.002	0.03	-10000	0	-0.63	2	2
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.016	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.01	0.048	-10000	0	-0.4	2	2
tumor necrosis factor receptor activity	0	0	0.002	36	-0.001	1	37
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	-0.01	0.091	-10000	0	-0.46	36	36
INS	0	0	-10000	0	-10000	0	0
PTEN	-0.002	0.038	-10000	0	-0.82	2	2
PDK2	-0.014	0.07	0.26	1	-0.34	39	40
EIF4EBP1	0.013	0.014	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-10000	0	0
PPP2R5D	0.019	0.015	-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	-0.003	1	3
EEF2	0	0.004	-10000	0	-10000	0	0
eIF4E/4E-BP1	0	0	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0	0	-10000	0	-10000	0	0
NFATC1	0.049	0.024	-10000	0	-10000	0	0
NFATC2	0.02	0.056	-10000	0	-0.29	6	6
NFATC3	-0.001	0.017	-10000	0	-0.53	1	1
YWHAE	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.013	0.094	-10000	0	-0.4	28	28
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	0.073	-10000	0	-0.52	11	11
BCL2/BAX	-0.021	0.12	-10000	0	-0.64	30	30
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	-0.001	0.016	-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	0.081	-10000	0	-0.58	11	11
Calcineurin A alpha-beta B1/BCL2	-0.027	0.15	-10000	0	-0.82	30	30
FKBP8	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.018	0.079	0.57	11	-10000	0	11
KPNB1	0	0	-10000	0	-10000	0	0
KPNA2	-0.03	0.087	-10000	0	-0.28	100	100
XPO1	0	0	-10000	0	-10000	0	0
SFN	-0.016	0.1	-10000	0	-0.54	27	27
MAP3K8	-0.005	0.062	-10000	0	-0.82	5	5
NFAT4/CK1 alpha	0	0.011	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.036	0.095	-10000	0	-0.47	3	3
CABIN1	0.013	0.095	-10000	0	-0.41	28	28
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	-0.01	0.053	-10000	0	-0.28	34	34
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	0.045	-10000	0	-0.63	1	1
YWHAB	0	0	-10000	0	-10000	0	0
MAPK8	-0.003	0.047	-10000	0	-0.82	3	3
MAPK9	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0	0.009	-10000	0	-0.28	1	1
NFAT1-c-4/YWHAQ	-0.002	0.018	-10000	0	-0.42	1	1
PRKCH	-0.001	0.027	-10000	0	-0.82	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	-0.007	0.036	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.003	0.025	-10000	0	-10000	0	0
PRKCB	-0.019	0.11	-10000	0	-0.82	16	16
PRKCE	-0.001	0.027	-10000	0	-0.82	1	1
JNK2/NFAT4	-0.001	0.016	-10000	0	-0.48	1	1
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0	0.009	-10000	0	-0.28	1	1
NUP214	0	0	-10000	0	-10000	0	0
PRKCZ	-0.001	0.027	-10000	0	-0.82	1	1
PRKCA	-0.02	0.12	-10000	0	-0.78	23	23
PRKCG	-0.011	0.053	-10000	0	-10000	0	0
PRKCQ	-0.035	0.16	-10000	0	-0.67	47	47
FKBP38/BCL2	-0.021	0.11	-10000	0	-0.63	30	30
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	0.049	0.037	-10000	0	-0.4	3	3
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	0.015	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.017	0.073	-10000	0	-0.52	11	11
NR4A1	-0.071	0.21	-10000	0	-0.73	82	82
GSK3B	0	0	-10000	0	-10000	0	0
positive T cell selection	-0.001	0.017	-10000	0	-0.52	1	1
NFAT1/CK1 alpha	-0.012	0.034	-10000	0	-0.3	1	1
RCH1/ KPNB1	-0.019	0.055	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
AKAP5	-0.016	0.069	-10000	0	-0.29	51	51
MEF2D	0	0.001	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	-0.001	0.016	-10000	0	-0.28	3	3
NFATc/p38 alpha	0.05	0.026	-10000	0	-10000	0	0
CREBBP	0	0.001	-10000	0	-10000	0	0
BCL2	-0.027	0.15	-10000	0	-0.82	30	30

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	-0.002	0.026	-9999	-10000	0	0
ELF1	-0.011	0.047	-9999	-0.38	11	11
CCNA2	-0.12	0.14	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-10000	0	0
JAK3	-0.005	0.035	-9999	-10000	0	0
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
JAK1	0	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.061	0.065	-9999	-0.6	4	4
SHC1	0	0	-9999	-10000	0	0
SP1	-0.003	0.034	-9999	-0.38	7	7
IL2RA	0.004	0.12	-9999	-1	11	11
IL2RB	-0.012	0.055	-9999	-0.28	38	38
SOS1	0	0	-9999	-10000	0	0
IL2RG	-0.016	0.081	-9999	-0.82	5	5
G1/S transition of mitotic cell cycle	0.011	0.11	-9999	-0.79	13	13
PTPN11	0	0	-9999	-10000	0	0
CCND2	0.021	0.093	-9999	-1	7	7
LCK	-0.018	0.1	-9999	-0.43	39	39
GRB2	0	0.009	-9999	-10000	0	0
IL2	-0.002	0.026	-9999	-0.28	8	8
CDK6	-0.008	0.078	-9999	-0.72	10	10
CCND3	0.066	0.058	-9999	-0.62	2	2

×

TCGA08_retinoblastoma

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.002	0.06	-10000	0	-0.71	6	6
CDKN2C	0.005	0.041	-10000	0	-0.82	2	2
CDKN2A	-0.047	0.11	-10000	0	-10000	0	0
CCND2	0.006	0.029	0.26	6	-0.16	7	13
RB1	-0.007	0.029	0.17	2	-0.26	6	8
CDK4	0.009	0.028	0.26	7	-10000	0	7
CDK6	0.006	0.033	0.28	6	-0.21	7	13
G1/S progression	-0.007	0.032	0.26	6	-0.17	2	8

×

VEGFR1 specific signals

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	-0.001	0.031	-9999	-0.93	1	1
VEGFR1 homodimer/NRP1	-0.001	0.031	-9999	-0.94	1	1
mol:DAG	0.038	0.034	-9999	-0.67	2	2
VEGFR1 homodimer/NRP1/VEGFR 121	-0.002	0.031	-9999	-0.87	1	1
CaM/Ca2+	-0.001	0.031	-9999	-0.63	2	2
HIF1A	0	0.013	-9999	-0.38	1	1
GAB1	0	0	-9999	-10000	0	0
AKT1	-0.002	0.032	-9999	-0.53	3	3
PLCG1	0.038	0.035	-9999	-0.68	2	2
NOS3	0.062	0.031	-9999	-0.58	2	2
CBL	0	0	-9999	-10000	0	0
mol:NO	0.062	0.03	-9999	-0.55	2	2
FLT1	0.028	0.035	-9999	-1	1	1
PGF	-0.001	0.029	-9999	-0.55	2	2
VEGFR1 homodimer/NRP2/VEGFR121	-0.003	0.045	-9999	-1.3	1	1
CALM1	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-10000	0	0
eNOS/Hsp90	-0.001	0.026	-9999	-0.66	1	1
endothelial cell proliferation	0.037	0.09	-9999	-0.88	3	3
mol:Ca2+	0.038	0.034	-9999	-0.66	2	2
MAPK3	0.04	0.083	-9999	-0.46	22	22
MAPK1	0.04	0.083	-9999	-0.46	22	22
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
PLGF homodimer	-0.001	0.029	-9999	-0.55	2	2
PRKACA	0	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.17	0.34	-9999	-0.82	191	191
VEGFA homodimer	-0.003	0.027	-9999	-0.28	9	9
VEGFR1 homodimer/VEGFA homodimer	-0.002	0.033	-9999	-0.93	1	1
platelet activating factor biosynthetic process	0.047	0.081	-9999	-0.44	22	22
PI3K	-0.002	0.035	-9999	-0.58	3	3
PRKCA	0.033	0.087	-9999	-0.5	22	22
PRKCB	0.034	0.081	-9999	-0.51	17	17
VEGFR1 homodimer/PLGF homodimer	-0.002	0.036	-9999	-0.74	2	2
VEGFA	-0.003	0.028	-9999	-0.28	9	9
VEGFB	0	0	-9999	-10000	0	0
mol:IP3	0.038	0.034	-9999	-0.67	2	2
RASA1	0.038	0.03	-9999	-0.86	1	1
NRP2	-0.001	0.029	-9999	-0.55	2	2
VEGFR1 homodimer	0.028	0.035	-9999	-1	1	1
VEGFB homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.082	0.16	-9999	-0.92	2	2
PTPN11	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.002	0.034	-9999	-0.57	3	3
mol:L-citrulline	0.062	0.03	-9999	-0.55	2	2
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.002	0.029	-9999	-0.82	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.002	0.03	-9999	-0.87	1	1
CD2AP	0	0.009	-9999	-0.28	1	1
PI3K/GAB1	-0.002	0.033	-9999	-0.55	3	3
PDPK1	-0.002	0.032	-9999	-0.54	3	3
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.002	0.03	-9999	-0.87	1	1
mol:NADP	0.062	0.03	-9999	-0.55	2	2
HSP90AA1	0	0.009	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.002	0.029	-9999	-0.81	1	1
VEGFR1 homodimer/NRP2	-0.002	0.046	-9999	-1.4	1	1

×

p38 MAPK 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
TRAF6/ASK1	-0.001	0.023	-10000	0	-0.49	2	2
TRAF2/ASK1	-0.002	0.027	-10000	0	-0.56	2	2
ATM	0	0	-10000	0	-10000	0	0
MAP2K3	0.027	0.038	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.029	0.056	-10000	0	-0.35	5	5
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.025	0.079	-10000	0	-10000	0	0
TXN	0	0.004	-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	0.027	-10000	0	-0.82	1	1
MAP3K7	0	0.009	-10000	0	-10000	0	0
MAP3K4	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.002	0.036	-10000	0	-0.63	3	3
TAK1/TAB family	0	0.01	0.22	2	-10000	0	2
RAC1/OSM/MEKK3	0	0.004	-10000	0	-10000	0	0
TRAF2	-0.001	0.013	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.005	0.017	-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	-0.074	0.22	-10000	0	-0.62	108	108
CCM2	0	0.009	-10000	0	-0.28	1	1
CaM/Ca2+/CAMKIIB	-0.048	0.15	-10000	0	-0.56	68	68
MAPK11	-0.002	0.039	-10000	0	-0.82	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.044	0.14	-10000	0	-0.51	70	70
OSM/MEKK3	0	0.006	-10000	0	-10000	0	0
TAOK1	-0.01	0.066	-10000	0	-0.45	20	20
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	0.039	-10000	0	-0.82	2	2
MAP3K10	0	0.009	-10000	0	-10000	0	0
MAP3K3	0	0	-10000	0	-10000	0	0
TRX/ASK1	-0.001	0.026	-10000	0	-0.55	2	2
GADD45/MTK1/MTK1	-0.009	0.029	-10000	0	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.008	0.057	-9999	-0.33	23	23
ITGA4	-0.003	0.029	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.007	0.046	-9999	-0.44	6	6
alpha4/beta1 Integrin	-0.002	0.018	-9999	-10000	0	0

×

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

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
BAG4	-0.004	0.04	-9999	-0.82	1	1
Caspase 8 (4 units)	-0.007	0.044	-9999	-1	1	1
NEF	-0.004	0.021	-9999	-0.22	3	3
NFKBIA	-0.001	0.011	-9999	-10000	0	0
BIRC3	-0.01	0.08	-9999	-0.83	8	8
CYCS	0.042	0.054	-9999	-0.96	1	1
RIPK1	0	0	-9999	-10000	0	0
CD247	-0.026	0.13	-9999	-0.72	27	27
MAP2K7	0.043	0.045	-9999	-0.82	1	1
protein ubiquitination	0.065	0.036	-9999	-10000	0	0
CRADD	0	0	-9999	-10000	0	0
DAXX	0	0	-9999	-10000	0	0
FAS	-0.003	0.047	-9999	-0.82	3	3
BID	-0.008	0.049	-9999	-1.1	1	1
NF-kappa-B/RelA/I kappa B alpha	-0.004	0.034	-9999	-0.34	8	8
TRADD	0	0	-9999	-10000	0	0
MAP3K5	-0.002	0.039	-9999	-0.82	2	2
CFLAR	0	0	-9999	-10000	0	0
FADD	-0.005	0.037	-9999	-0.28	16	16
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.004	0.034	-9999	-0.34	8	8
MAPK8	0.048	0.05	-9999	-0.5	4	4
APAF1	0	0	-9999	-10000	0	0
TRAF1	-0.001	0.018	-9999	-0.28	4	4
TRAF2	-0.001	0.013	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.009	0.053	-9999	-0.39	10	10
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.002	0.033	-9999	-0.38	2	2
CHUK	0.067	0.037	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.004	0.045	-9999	-0.61	4	4
TCRz/NEF	-0.024	0.11	-9999	-0.57	30	30
TNF	-0.018	0.11	-9999	-0.82	14	14
FASLG	-0.002	0.13	-9999	-0.62	30	30
NFKB1	-0.001	0.011	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.073	-9999	-0.55	15	15
CASP6	-0.003	0.03	-9999	-0.71	1	1
CASP7	0.074	0.075	-9999	-0.64	8	8
RELA	-0.001	0.011	-9999	-10000	0	0
CASP2	0	0	-9999	-10000	0	0
CASP3	0.074	0.075	-9999	-0.64	8	8
TNFRSF1A	0	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.003	0.028	-9999	-0.63	1	1
CASP8	0	0	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
MAP3K14	0.062	0.04	-9999	-0.36	1	1
APAF-1/Caspase 9	-0.008	0.054	-9999	-0.54	8	8
BCL2	0.039	0.098	-9999	-0.44	32	32

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.014	0.091	-9999	-0.63	19	19
AKT1	0.085	0.043	-9999	-0.69	2	2
PTK2B	-0.011	0.075	-9999	-0.96	2	2
VEGFR2 homodimer/Frs2	-0.003	0.045	-9999	-0.92	2	2
CAV1	-0.17	0.34	-9999	-0.82	191	191
CALM1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.004	0.042	-9999	-0.86	2	2
endothelial cell proliferation	0.086	0.069	-9999	-0.64	3	3
mol:Ca2+	0.054	0.041	-9999	-0.77	2	2
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.001	0.039	-9999	-0.81	2	2
RP11-342D11.1	0.046	0.041	-9999	-0.78	2	2
CDH5	-0.005	0.061	-9999	-0.82	5	5
VEGFA homodimer	-0.001	0.011	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
SHC2	-0.023	0.14	-9999	-0.82	25	25
HRAS/GDP	-0.001	0.031	-9999	-0.66	2	2
SH2D2A	-0.03	0.09	-9999	-0.28	98	98
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0	0.032	-9999	-0.63	2	2
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.014	0.055	-9999	-0.77	3	3
VEGFR1 homodimer	-0.001	0.027	-9999	-0.82	1	1
SHC/GRB2/SOS1	-0.001	0.036	-9999	-0.74	2	2
GRB10	0.054	0.041	-9999	-0.77	2	2
PTPN11	0	0	-9999	-10000	0	0
GRB2	0	0.009	-9999	-10000	0	0
PAK1	-0.006	0.041	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.003	0.062	-9999	-1.2	2	2
HRAS	-0.001	0.013	-9999	-0.28	2	2
VEGF/Rho/ROCK1/Integrin Complex	-0.006	0.042	-9999	-0.52	2	2
HIF1A	0	0	-9999	-10000	0	0
FRS2	-0.003	0.029	-9999	-0.28	10	10
oxygen and reactive oxygen species metabolic process	-0.001	0.038	-9999	-0.8	2	2
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.002	0.039	-9999	-0.82	2	2
Nck/Pak	-0.004	0.026	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.003	0.053	-9999	-1.1	2	2
mol:GDP	-0.001	0.034	-9999	-0.71	2	2
mol:NADP	0.076	0.03	-9999	-0.52	2	2
eNOS/Hsp90	0.077	0.028	-9999	-0.48	2	2
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
mol:IP3	0.054	0.041	-9999	-0.78	2	2
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	-0.001	0.029	-9999	-0.55	2	2
VEGFA	-0.003	0.027	-9999	-0.27	9	9
VEGFC	0	0	-9999	-10000	0	0
FAK1/Vinculin	-0.007	0.056	-9999	-0.89	2	2
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.01	0.081	-9999	-0.51	20	20
PTPN6	-0.001	0.013	-9999	-0.28	2	2
EPAS1	-0.001	0.018	-9999	-0.38	2	2
mol:L-citrulline	0.076	0.03	-9999	-0.52	2	2
ITGAV	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0	0.04	-9999	-0.81	2	2
VEGFR2 homodimer/VEGFA homodimer	-0.001	0.041	-9999	-0.85	2	2
VEGFR2/3 heterodimer	-0.003	0.058	-9999	-0.95	3	3
VEGFB	0	0	-9999	-10000	0	0
MAPK11	0.059	0.043	-9999	-0.79	2	2
VEGFR2 homodimer	0.033	0.049	-9999	-1	2	2
FLT1	-0.001	0.027	-9999	-0.82	1	1
NEDD4	0	0	-9999	-10000	0	0
MAPK3	0.055	0.061	-9999	-0.79	3	3
MAPK1	0.055	0.061	-9999	-0.79	3	3
VEGFA145/NRP2	-0.003	0.028	-9999	-0.63	1	1
VEGFR1/2 heterodimer	-0.003	0.055	-9999	-1.2	2	2
KDR	0.033	0.05	-9999	-1	2	2
VEGFA165/NRP1/VEGFR2 homodimer	-0.001	0.049	-9999	-1	2	2
SRC	0	0.009	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.057	0.061	-9999	-0.8	3	3
PI3K	-0.003	0.047	-9999	-0.9	2	2
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.003	0.041	-9999	-0.86	2	2
FES	0.053	0.051	-9999	-0.59	5	5
GAB1	-0.002	0.045	-9999	-0.94	2	2
VEGFR2 homodimer/VEGFA homodimer/Src	-0.003	0.041	-9999	-0.86	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	-0.54	5	5
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.003	0.044	-9999	-0.73	3	3
PI3K/GAB1	-0.002	0.038	-9999	-0.71	2	2
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.002	0.041	-9999	-0.78	2	2
PRKACA	0	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.003	0.054	-9999	-0.89	3	3
HSP90AA1	0	0.009	-9999	-10000	0	0
CDC42	0.055	0.042	-9999	-0.8	2	2
actin cytoskeleton reorganization	-0.014	0.054	-9999	-0.76	3	3
PTK2	0.06	0.071	-9999	-0.99	2	2
EDG1	0.046	0.041	-9999	-0.78	2	2
mol:DAG	0.054	0.041	-9999	-0.78	2	2
CaM/Ca2+	-0.002	0.034	-9999	-0.72	2	2
MAP2K3	0.061	0.046	-9999	-0.59	4	4
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.001	0.039	-9999	-0.81	2	2
PLCG1	0.055	0.042	-9999	-0.8	2	2
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.001	0.042	-9999	-0.69	3	3
IQGAP1	0	0	-9999	-10000	0	0
YES1	-0.001	0.027	-9999	-0.82	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.003	0.041	-9999	-0.86	2	2
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.003	0.041	-9999	-0.86	2	2
cell migration	0.084	0.061	-9999	-0.78	2	2
mol:PI-3-4-5-P3	-0.002	0.042	-9999	-0.8	2	2
FYN	-0.001	0.027	-9999	-0.82	1	1
VEGFB/NRP1	-0.002	0.035	-9999	-0.73	2	2
mol:NO	0.076	0.03	-9999	-0.52	2	2
PXN	0	0	-9999	-10000	0	0
HRAS/GTP	-0.002	0.031	-9999	-0.66	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.001	0.039	-9999	-0.81	2	2
VHL	0	0	-9999	-10000	0	0
ITGB3	-0.018	0.12	-9999	-0.82	19	19
NOS3	0.078	0.033	-9999	-0.6	2	2
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.016	0.089	-9999	-0.51	27	27
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.05	0.087	-9999	-0.48	22	22
PRKCB	0.051	0.085	-9999	-0.52	16	16
VCL	0	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.001	0.038	-9999	-0.78	2	2
VEGFR1/2 heterodimer/VEGFA homodimer	-0.003	0.053	-9999	-1.1	2	2
VEGFA165/NRP2	-0.003	0.028	-9999	-0.63	1	1
MAPKKK cascade	0	0.033	-9999	-0.65	2	2
NRP2	-0.001	0.029	-9999	-0.55	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	-0.007	0.056	-9999	-0.89	2	2
MAP3K13	0.053	0.048	-9999	-0.62	4	4
PDPK1	0.078	0.042	-9999	-0.68	2	2

×

Regulation of cytoplasmic and nuclear SMAD2/3 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
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	-0.009	0.026	-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	-0.005	0.055	-9999	-0.63	7	7
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	-0.006	0.072	-9999	-0.82	7	7
UBE2I	0	0	-9999	-10000	0	0
NUP153	0	0.009	-9999	-10000	0	0
KPNA2	-0.03	0.087	-9999	-0.28	100	100
PIAS4	0	0	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0	0.015	-10000	0	-10000	0	0
oxygen homeostasis	0.013	0.012	-10000	0	-10000	0	0
TCEB2	-0.003	0.028	-10000	0	-10000	0	0
TCEB1	-0.001	0.016	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.003	0.024	-10000	0	-10000	0	0
EPO	0.16	0.14	-10000	0	-0.5	1	1
FIH (dimer)	0.023	0.011	-10000	0	-10000	0	0
APEX1	0.022	0.014	-10000	0	-0.3	1	1
SERPINE1	0.17	0.14	-10000	0	-0.59	1	1
FLT1	-0.001	0.07	-10000	0	-1.4	2	2
ADORA2A	0.15	0.15	-10000	0	-0.54	2	2
germ cell development	0.16	0.14	-10000	0	-0.61	4	4
SLC11A2	0.17	0.14	-10000	0	-0.59	1	1
BHLHE40	0.17	0.14	-10000	0	-0.97	2	2
HIF1AN	0.023	0.011	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.019	0.065	-10000	0	-0.38	1	1
ETS1	0.024	0.041	-10000	0	-0.86	2	2
CITED2	0.001	0.01	-10000	0	-10000	0	0
KDR	-0.001	0.082	-10000	0	-1.7	2	2
PGK1	0.17	0.14	-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	0.18	0.14	-10000	0	-0.64	2	2
EPAS1	0.098	0.072	-10000	0	-0.41	1	1
SP1	0.018	0.002	-10000	0	-10000	0	0
ABCG2	0.14	0.24	-10000	0	-0.71	57	57
EFNA1	0.17	0.14	-10000	0	-0.59	1	1
FXN	0.16	0.14	-10000	0	-0.57	1	1
POU5F1	0.17	0.14	-10000	0	-0.64	4	4
neuron apoptosis	-0.16	0.15	0.62	2	-10000	0	2
EP300	0	0	-10000	0	-10000	0	0
EGLN3	0	0.079	-10000	0	-0.27	72	72
EGLN2	0.022	0.022	-10000	0	-0.29	1	1
EGLN1	0.022	0.03	-10000	0	-0.84	1	1
VHL/Elongin B/Elongin C	-0.002	0.015	-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	3	3
TWIST1	0.15	0.19	-10000	0	-0.7	29	29
ELK1	0.018	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.012	0.057	-10000	0	-10000	0	0
VEGFA	0.17	0.14	-10000	0	-0.55	2	2
CREBBP	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.006	0.063	-9999	-0.51	14	14
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.007	0.052	-9999	-0.42	14	14
SUMO1	0	0	-9999	-10000	0	0
ZFPM1	-0.002	0.022	-9999	-0.28	6	6
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
FKBP3	0	0	-9999	-10000	0	0
Histones	-0.003	0.026	-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	-0.007	0.046	-9999	-0.37	14	14
I kappa B alpha/HDAC1	-0.004	0.031	-9999	-10000	0	0
SAP18	0	0	-9999	-10000	0	0
RELA	-0.006	0.04	-9999	-0.32	14	14
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
HDAC3/TR2	-0.004	0.031	-9999	-10000	0	0
NuRD/MBD3 Complex	0	0.001	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.005	0.036	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.024	0.13	-9999	-0.82	23	23
GATA1	-0.003	0.03	-9999	-0.28	11	11
Mad/Max	0	0.006	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0	0.004	-9999	-10000	0	0
RBBP7	-0.002	0.026	-9999	-0.28	8	8
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	-0.005	0.035	-9999	-0.28	14	14
KAT2B	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0	0	-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	0.018	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	-0.001	0.027	-9999	-0.82	1	1
YY1/HDAC3	-0.004	0.027	-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	-0.094	0.17	-9999	-0.39	218	218
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	0.031	-9999	-10000	0	0
MBD3L2	-0.001	0.013	-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	-0.005	0.035	-9999	-10000	0	0
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	0.009	-9999	-0.28	1	1
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	0.007	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.024	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.005	0.035	-9999	-0.28	14	14
histone deacetylation	0.045	0.003	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.004	0.028	-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	-0.018	0.084	-9999	-0.5	23	23
GATA1/HDAC1	-0.002	0.019	-9999	-10000	0	0
GATA1/HDAC3	-0.006	0.034	-9999	-10000	0	0
CHD4	0	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.013	0.081	-9999	-0.63	14	14
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	0.025	-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	0.01	-9999	-10000	0	0
GATA1/Fog1	-0.003	0.024	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.018	0.11	-9999	-0.82	14	14
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	-0.007	0.054	-9999	-0.44	14	14
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	0.009	-9999	-0.28	1	1
MBD2	0	0	-9999	-10000	0	0

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.004	0.039	-9999	-0.54	4	4
PDGFB-D/PDGFRB/SLAP	-0.003	0.034	-9999	-0.63	2	2
PDGFB-D/PDGFRB/APS/CBL	-0.007	0.037	-9999	-0.54	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	-0.003	0.04	-9999	-0.57	4	4
PIK3CA	0	0.009	-9999	-10000	0	0
FGR	-0.003	0.035	-9999	-0.56	3	3
mol:Ca2+	0.034	0.038	-9999	-0.67	2	2
MYC	0.039	0.14	-9999	-0.82	22	22
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.002	0.023	-9999	-0.44	2	2
LRP1/PDGFRB/PDGFB	-0.007	0.07	-9999	-0.65	10	10
GRB10	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0.033	0.039	-9999	-0.68	2	2
PTEN	-0.002	0.039	-9999	-0.82	2	2
GRB2	0	0.009	-9999	-10000	0	0
GRB7	-0.021	0.076	-9999	-0.82	1	1
PDGFB-D/PDGFRB/SHP2	-0.001	0.029	-9999	-0.63	2	2
PDGFB-D/PDGFRB/GRB10	-0.001	0.029	-9999	-0.63	2	2
cell cycle arrest	-0.003	0.034	-9999	-0.63	2	2
HRAS	-0.001	0.013	-9999	-0.28	2	2
HIF1A	0.055	0.043	-9999	-10000	0	0
GAB1	0.036	0.047	-9999	-0.66	2	2
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.04	0.046	-9999	-0.6	2	2
PDGFB-D/PDGFRB	-0.002	0.03	-9999	-0.56	2	2
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.001	0.029	-9999	-0.63	2	2
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.005	0.044	-9999	-0.57	4	4
positive regulation of MAPKKK cascade	-0.001	0.029	-9999	-0.63	2	2
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
mol:IP3	0.034	0.039	-9999	-0.69	2	2
E5	0	0.001	-9999	-10000	0	0
CSK	0	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.015	0.058	-9999	-0.63	3	3
SHB	-0.001	0.029	-9999	-0.55	2	2
BLK	-0.001	0.049	-9999	-0.63	5	5
PTPN2	0	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.001	0.029	-9999	-0.63	2	2
BCAR1	0	0	-9999	-10000	0	0
VAV2	0.04	0.055	-9999	-0.56	3	3
CBL	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.001	0.029	-9999	-0.63	2	2
LCK	-0.009	0.072	-9999	-0.6	13	13
PDGFRB	-0.001	0.039	-9999	-0.83	2	2
ACP1	0	0	-9999	-10000	0	0
HCK	-0.002	0.028	-9999	-0.52	2	2
ABL1	0.034	0.041	-9999	-0.61	2	2
PDGFB-D/PDGFRB/CBL	0.035	0.049	-9999	-0.75	2	2
PTPN1	-0.003	0.03	-9999	-0.29	1	1
SNX15	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
STAT1	-0.006	0.04	-9999	-0.28	19	19
cell proliferation	0.04	0.12	-9999	-0.71	22	22
SLA	-0.002	0.026	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.002	0.025	-9999	-0.42	3	3
SRC	-0.002	0.027	-9999	-0.52	2	2
PI3K	-0.009	0.035	-9999	-0.4	1	1
PDGFB-D/PDGFRB/GRB7/SHC	-0.011	0.046	-9999	-0.55	3	3
SH2B2	-0.011	0.055	-9999	-0.28	37	37
PLCgamma1/SPHK1	-0.003	0.042	-9999	-0.59	4	4
LYN	-0.002	0.027	-9999	-0.52	2	2
LRP1	-0.009	0.086	-9999	-0.82	10	10
SOS1	0	0	-9999	-10000	0	0
STAT5B	-0.003	0.047	-9999	-0.82	3	3
STAT5A	-0.006	0.072	-9999	-0.82	7	7
NCK1-2/p130 Cas	-0.002	0.022	-9999	-0.44	2	2
SPHK1	-0.005	0.05	-9999	-0.36	14	14
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.034	0.039	-9999	-0.69	2	2
PLCG1	0.034	0.04	-9999	-0.71	2	2
NHERF/PDGFRB	-0.013	0.046	-9999	-0.54	2	2
YES1	-0.003	0.034	-9999	-0.55	3	3
cell migration	-0.013	0.045	-9999	-0.54	2	2
SHC/Grb2/SOS1	-0.002	0.022	-9999	-0.44	2	2
SLC9A3R2	0	0.009	-9999	-10000	0	0
SLC9A3R1	-0.024	0.079	-9999	-0.28	80	80
NHERF1-2/PDGFRB/PTEN	-0.012	0.045	-9999	-0.5	4	4
FYN	-0.003	0.048	-9999	-0.91	2	2
DOK1	-0.001	0.027	-9999	-0.5	2	2
HRAS/GTP	0	0.009	-9999	-10000	0	0
PDGFB	0	0	-9999	-10000	0	0
RAC1	0.047	0.078	-9999	-0.43	22	22
PRKCD	0.003	0.029	-9999	-0.5	2	2
FER	0	0.051	-9999	-0.5	8	8
MAPKKK cascade	-0.002	0.022	-9999	-0.43	2	2
RASA1	0.003	0.029	-9999	-0.5	2	2
NCK1	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
p62DOK/Csk	-0.002	0.024	-9999	-0.46	2	2
PDGFB-D/PDGFRB/SHB	-0.002	0.037	-9999	-0.63	3	3
chemotaxis	0.034	0.04	-9999	-0.59	2	2
STAT1-3-5/STAT1-3-5	-0.008	0.054	-9999	-0.46	11	11
Bovine Papilomavirus E5/PDGFRB	-0.001	0.03	-9999	-0.64	2	2
PTPRJ	0	0	-9999	-10000	0	0

×

EPO signaling 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
BCL2L1	0.058	0.076	-9999	-0.53	1	1
CRKL	0.028	0.049	-9999	-0.51	1	1
mol:DAG	-0.001	0.028	-9999	-0.4	1	1
HRAS	-0.005	0.021	-9999	-0.41	1	1
MAPK8	0.013	0.059	-9999	-0.53	3	3
RAP1A	0.028	0.049	-9999	-0.51	1	1
GAB1	0.028	0.049	-9999	-0.51	1	1
MAPK14	0.014	0.05	-9999	-10000	0	0
EPO	-0.036	0.11	-9999	-0.3	10	10
PLCG1	-0.001	0.028	-9999	-0.41	1	1
EPOR/TRPC2/IP3 Receptors	0.012	0.01	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.024	0.068	-9999	-0.65	6	6
GAB1/SHC/GRB2/SOS1	-0.007	0.023	-9999	-0.44	1	1
EPO/EPOR (dimer)	-0.029	0.063	-9999	-10000	0	0
IRS2	0.008	0.12	-9999	-0.49	39	39
STAT1	0.049	0.056	-9999	-0.52	1	1
STAT5B	-0.004	0.046	-9999	-0.45	4	4
cell proliferation	0.022	0.055	-9999	-0.49	3	3
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.006	0.023	-9999	-0.41	1	1
TEC	0.027	0.055	-9999	-0.49	3	3
SOCS3	-0.005	0.067	-9999	-0.82	6	6
STAT1 (dimer)	0.048	0.056	-9999	-0.51	1	1
JAK2	0	0.028	-9999	-0.84	1	1
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
EPO/EPOR (dimer)/JAK2	0.054	0.043	-9999	-0.54	1	1
EPO/EPOR	-0.029	0.063	-9999	-10000	0	0
LYN	0.012	0.002	-9999	-10000	0	0
TEC/VAV2	-0.012	0.036	-9999	-0.47	3	3
elevation of cytosolic calcium ion concentration	0.012	0.01	-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	-0.001	0.028	-9999	-0.4	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.026	0.091	-9999	-0.48	22	22
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	0.032	-9999	-0.33	7	7
PTPN6	0.021	0.051	-9999	-0.53	1	1
TEC/VAV2/GRB2	-0.01	0.033	-9999	-0.48	2	2
EPOR	0.012	0.01	-9999	-10000	0	0
INPP5D	0	0	-9999	-10000	0	0
mol:GDP	-0.007	0.023	-9999	-0.44	1	1
SOS1	0	0	-9999	-10000	0	0
PLCG2	-0.001	0.029	-9999	-0.55	2	2
CRKL/CBL/C3G	-0.009	0.025	-9999	-0.47	1	1
VAV2	0.028	0.049	-9999	-0.51	1	1
CBL	0.028	0.049	-9999	-0.51	1	1
SHC/Grb2/SOS1	0.005	0.03	-9999	-0.47	1	1
STAT5A	-0.006	0.058	-9999	-0.49	8	8
GRB2	0	0.009	-9999	-10000	0	0
STAT5 (dimer)	0.057	0.088	-9999	-0.62	4	4
LYN/PLCgamma2	-0.001	0.022	-9999	-0.63	1	1
PTPN11	0	0	-9999	-10000	0	0
BTK	0.027	0.05	-9999	-0.51	1	1
BCL2	0.036	0.19	-9999	-1	30	30

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.004	0.025	-9999	-0.42	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	0.029	-9999	-10000	0	0
alpha4/beta7 Integrin/MAdCAM1	-0.009	0.042	-9999	-0.46	3	3
EPO	-0.047	0.1	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.007	0.046	-9999	-0.44	6	6
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.002	0.018	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.03	0.066	-9999	-10000	0	0
lamellipodium assembly	0	0.015	-9999	-0.41	1	1
PIK3CA	0	0.009	-9999	-10000	0	0
PI3K	-0.001	0.022	-9999	-0.63	1	1
ARF6	0	0	-9999	-10000	0	0
JAK2	-0.009	0.025	-9999	-0.52	1	1
PXN	0	0	-9999	-10000	0	0
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
MADCAM1	-0.011	0.053	-9999	-0.28	35	35
cell adhesion	-0.009	0.042	-9999	-0.46	3	3
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
SRC	-0.006	0.046	-9999	-0.5	7	7
ITGB7	-0.008	0.057	-9999	-0.33	23	23
RAC1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.007	0.051	-9999	-0.55	7	7
p130Cas/Crk/Dock1	-0.004	0.037	-9999	-10000	0	0
VCAM1	-0.008	0.075	-9999	-0.57	13	13
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	-0.46	7	7
EPOR	0	0.009	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
GIT1	-0.001	0.018	-9999	-0.28	4	4
Rac1/GTP	0	0.015	-9999	-0.42	1	1

×

ceramide signaling pathway

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.044	0.05	-10000	0	-0.56	1	1
BAG4	-0.004	0.04	-10000	0	-0.82	1	1
BAD	0.032	0.018	-10000	0	-10000	0	0
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.082	-10000	0	-0.82	8	8
BAX	0.031	0.02	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.015	0.014	-10000	0	-0.1	2	2
IKBKB	0.05	0.048	-10000	0	-0.52	1	1
MAP2K2	0.044	0.026	-10000	0	-0.48	1	1
MAP2K1	0.044	0.026	-10000	0	-0.48	1	1
SMPD1	0.02	0.014	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.048	0.052	-10000	0	-0.46	3	3
MAP2K4	0.038	0.024	-10000	0	-0.41	1	1
protein ubiquitination	0.052	0.048	-10000	0	-0.53	1	1
EnzymeConsortium:2.7.1.37	0.049	0.029	-10000	0	-0.51	1	1
response to UV	0	0	-10000	0	-0.003	1	1
RAF1	0.038	0.027	-10000	0	-0.52	1	1
CRADD	0	0	-10000	0	-10000	0	0
mol:ceramide	0.025	0.019	-10000	0	-0.17	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	0.019	-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	0.026	-10000	0	-0.47	1	1
MAPK1	0.046	0.026	-10000	0	-0.47	1	1
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.042	0.054	-10000	0	-0.48	3	3
KSR1	0.032	0.027	-10000	0	-0.55	1	1
MAPK8	0.042	0.035	-10000	0	-0.42	4	4
TRAF2	-0.001	0.013	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-0.002	1	1
CHUK	0.05	0.047	-10000	0	-0.52	1	1
TNF R/SODD	-0.003	0.028	-10000	0	-0.63	1	1
TNF	-0.018	0.11	-10000	0	-0.83	14	14
CYCS	0.037	0.026	0.15	25	-10000	0	25
IKBKG	0.05	0.047	-10000	0	-0.52	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.037	0.052	-10000	0	-0.6	1	1
RELA	0	0	-10000	0	-10000	0	0
RIPK1	0	0.001	-10000	0	-10000	0	0
AIFM1	0.037	0.026	0.15	25	-10000	0	25
TNF/TNF R/SODD	-0.013	0.073	-10000	0	-0.55	15	15
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	0.044	0.049	-10000	0	-0.56	1	1
response to hydrogen peroxide	0	0	-10000	0	-0.003	1	1
BCL2	-0.027	0.15	-10000	0	-0.82	30	30

×

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	0.036	-9999	-10000	0	0
PLK1	0.014	0.11	-9999	-0.6	1	1
CDKN1B	0.082	0.066	-9999	-0.55	3	3
FOXO3	0.045	0.096	-9999	-0.51	5	5
KAT2B	0.008	0.012	-9999	-10000	0	0
FOXO1/SIRT1	0.007	0.037	-9999	-0.33	8	8
CAT	0.048	0.11	-9999	-1.1	3	3
CTNNB1	0	0	-9999	-10000	0	0
AKT1	0.015	0.011	-9999	-10000	0	0
FOXO1	0.032	0.038	-9999	-0.37	8	8
MAPK10	-0.044	0.19	-9999	-0.47	144	144
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.063	0.087	-9999	-10000	0	0
response to oxidative stress	0.005	0.011	-9999	-10000	0	0
FOXO3A/SIRT1	-0.012	0.058	-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	-0.003	0.031	-9999	-0.34	1	1
mol:GDP	0.005	0.011	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
GADD45A	0.069	0.058	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.068	0.028	-9999	-10000	0	0
MST1	-0.003	0.097	-9999	-0.79	13	13
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.001	0.042	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
MAPK8	0.035	0.03	-9999	-0.47	3	3
MAPK9	0.036	0.006	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
YWHAZ	-0.001	0.016	-9999	-0.28	3	3
SIRT1	0.002	0.007	-9999	-10000	0	0
SOD2	0.093	0.069	-9999	-10000	0	0
RBL2	0.062	0.072	-9999	-10000	0	0
RAL/GDP	0.011	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	0.014	0.13	-9999	-1.5	6	6
SKP2	0	0	-9999	-10000	0	0
USP7	0	0.001	-9999	-10000	0	0
IKBKB	0.008	0.017	-9999	-10000	0	0
CCNB1	0.038	0.1	-9999	-0.54	3	3
FOXO1-3a-4/beta catenin	-0.007	0.034	-9999	-0.41	3	3
proteasomal ubiquitin-dependent protein catabolic process	-0.003	0.031	-9999	-0.34	1	1
CSNK1A1	0	0	-9999	-10000	0	0
SGK1	0.005	0.057	-9999	-0.83	4	4
CSNK1G3	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
ZFAND5	0.067	0.077	-9999	-10000	0	0
SFN	-0.016	0.1	-9999	-0.54	27	27
CDK2	0.002	0.005	-9999	-10000	0	0
FOXO3A/14-3-3	0.022	0.051	-9999	-10000	0	0
CREBBP	0.002	0.005	-9999	-10000	0	0
FBXO32	0.047	0.12	-9999	-1.4	3	3
BCL6	0.059	0.1	-9999	-1.2	3	3
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0

×

Atypical NF-kappaB 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
BCL3/RelA	0	0.008	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.003	0.041	-9999	-0.55	5	5
NF kappa B1 p50/RelA/I kappa B alpha	-0.003	0.025	-9999	-10000	0	0
NFKBIA	0.024	0.034	-9999	-0.28	11	11
MAPK14	0	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0	0.006	-9999	-10000	0	0
ARRB2	0	0	-9999	-10000	0	0
REL	-0.005	0.061	-9999	-0.82	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	-0.001	0.009	-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	0.009	-9999	-10000	0	0
NF kappa B1 p50 dimer	0	0.008	-9999	-10000	0	0
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
NFKB1	0.022	0.009	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	-0.003	0.03	-9999	-0.27	11	11
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.003	0.024	-9999	-10000	0	0
SRC	0	0.009	-9999	-10000	0	0
PI3K	-0.001	0.022	-9999	-0.63	1	1
NF kappa B1 p50/RelA	-0.004	0.03	-9999	-0.28	11	11
IKBKB	-0.001	0.013	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
SYK	0	0.009	-9999	-0.28	1	1
I kappa B alpha/PIK3R1	-0.004	0.032	-9999	-0.46	1	1
cell death	-0.003	0.023	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.003	0.041	-9999	-0.55	5	5
LCK	-0.018	0.1	-9999	-0.43	39	39
BCL3	-0.001	0.013	-9999	-0.28	2	2

×

Canonical NF-kappaB 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	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	0.034	-9999	-10000	0	0
ERC1	0	0	-9999	-10000	0	0
RIP2/NOD2	-0.006	0.034	-9999	-0.35	1	1
NFKBIA	0.047	0	-9999	-10000	0	0
BIRC2	0	0	-9999	-10000	0	0
IKBKB	-0.001	0.013	-9999	-10000	0	0
RIPK2	-0.002	0.021	-9999	-0.28	5	5
IKBKG	0	0.001	-9999	-10000	0	0
IKK complex/A20	-0.005	0.05	-9999	-10000	0	0
NEMO/A20/RIP2	-0.002	0.021	-9999	-0.28	5	5
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	-0.009	0.048	-9999	-0.28	28	28
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	-0.013	0.081	-9999	-0.63	14	14
TRAF6	0	0	-9999	-10000	0	0
PRKCA	-0.02	0.12	-9999	-0.78	23	23
CHUK	0	0	-9999	-10000	0	0
UBE2D3	0	0	-9999	-10000	0	0
TNF	-0.018	0.11	-9999	-0.82	14	14
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	-0.009	0.06	-9999	-10000	0	0

×

Circadian rhythm 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
chromatin modification	0.001	0.019	-9999	-10000	0	0
CLOCK	0.01	0.055	-9999	-0.82	4	4
TIMELESS/CRY2	-0.001	0.008	-9999	-10000	0	0
DEC1/BMAL1	-0.001	0.011	-9999	-10000	0	0
ATR	0	0	-9999	-10000	0	0
NR1D1	0.041	0.013	-9999	-10000	0	0
ARNTL	0.014	0.002	-9999	-10000	0	0
TIMELESS	0.041	0.016	-9999	-10000	0	0
NPAS2	0.009	0.057	-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	-10000	0	0
mol:HEME	0.013	0.003	-9999	-10000	0	0
PER1	-0.018	0.12	-9999	-0.82	20	20
BMAL/CLOCK/NPAS2	-0.005	0.051	-9999	-0.54	8	8
BMAL1/CLOCK	0.044	0.04	-9999	-0.41	4	4
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	0.07	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.001	0.018	-9999	-0.28	4	4

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.013	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	-0.12	0.15	-9999	-0.36	11	11
YWHAZ	-0.001	0.016	-9999	-0.28	3	3
CALM1	0	0	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
TBC1D4	0.021	0.022	-9999	-0.64	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	0.006	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
ASIP	-0.002	0.021	-9999	-0.28	5	5
PRKCI	0	0.009	-9999	-10000	0	0
AS160/CaM/Ca2+	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
GYS1	0.031	0	-9999	-10000	0	0
PRKCZ	-0.001	0.027	-9999	-0.82	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	0.031	-9999	-10000	0	0
VAMP2	0	0	-9999	-10000	0	0
SLC2A4	-0.14	0.16	-9999	-0.39	11	11
STX4	0	0	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
SFN	-0.016	0.1	-9999	-0.54	27	27
LNPEP	-0.004	0.054	-9999	-0.82	4	4
YWHAE	0	0	-9999	-10000	0	0

×

IFN-gamma 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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.012	0.036	-9999	-0.45	1	1
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	0.027	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.001	0.018	-9999	-0.55	1	1
antigen processing and presentation of peptide antigen via MHC class I	-0.008	0.035	-9999	-0.41	1	1
CaM/Ca2+	0.011	0.032	-9999	-0.42	1	1
RAP1A	0	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.011	0.034	-9999	-0.42	1	1
AKT1	-0.006	0.022	-9999	-10000	0	0
MAP2K1	0.041	0.039	-9999	-10000	0	0
MAP3K11	0.03	0.04	-9999	-0.42	1	1
IFNGR1	0.001	0.002	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.026	0.1	-9999	-0.42	22	22
Rap1/GTP	-0.004	0.013	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.012	0.035	-9999	-0.46	1	1
CEBPB	0.075	0.035	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.01	0.057	-9999	-1.3	1	1
STAT1	-0.011	0.034	-9999	-0.42	1	1
CALM1	0	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.038	0.095	-9999	-0.28	2	2
PIK3CA	0	0.009	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	-0.009	0.03	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	0	0.009	-9999	-10000	0	0
mol:Ca2+	0.011	0.034	-9999	-0.44	1	1
MAPK3	0.054	0.035	-9999	-10000	0	0
STAT1 (dimer)	-0.003	0.051	-9999	-0.61	1	1
MAPK1	0.054	0.035	-9999	-10000	0	0
JAK2	0	0.027	-9999	-0.82	1	1
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
JAK1	0.001	0.002	-9999	-10000	0	0
CAMK2D	-0.003	0.047	-9999	-0.82	3	3
DAPK1	0.069	0.031	-9999	-10000	0	0
SMAD7	0.05	0.036	-9999	-10000	0	0
CBL/CRKL/C3G	-0.006	0.019	-9999	-10000	0	0
PI3K	0.009	0.032	-9999	-0.41	2	2
IFNG	-0.038	0.095	-9999	-0.28	2	2
apoptosis	0.053	0.027	-9999	-10000	0	0
CAMK2G	0	0	-9999	-10000	0	0
STAT3 (dimer)	0	0	-9999	-10000	0	0
CAMK2A	-0.009	0.048	-9999	-0.28	28	28
CAMK2B	-0.074	0.22	-9999	-0.62	108	108
FRAP1	0.042	0.038	-9999	-10000	0	0
PRKCD	-0.006	0.023	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
negative regulation of cell growth	-0.008	0.035	-9999	-0.41	1	1
PTPN2	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
IRF1	0.064	0.045	-9999	-10000	0	0
STAT1 (dimer)/PIASy	-0.009	0.032	-9999	-0.4	1	1
SOCS1	0.001	0.052	-9999	-1.5	1	1
mol:GDP	-0.006	0.018	-9999	-10000	0	0
CASP1	0.049	0.043	-9999	-0.36	4	4
PTGES2	0	0.009	-9999	-0.28	1	1
IRF9	0.057	0.018	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.006	0.027	-9999	-0.4	2	2
RAP1/GDP	-0.004	0.013	-9999	-10000	0	0
CBL	-0.009	0.025	-9999	-0.42	1	1
MAP3K1	0.031	0.04	-9999	-0.42	1	1
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	0.035	-9999	-0.41	1	1
PTPN11	-0.011	0.029	-9999	-0.44	1	1
CREBBP	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	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	0.02	0.3	2	-10000	0	2
DAPP1	0.036	0.053	-10000	0	-0.61	3	3
Src family/SYK family/BLNK-LAT/BTK-ITK	0.047	0.078	-10000	0	-0.57	8	8
mol:DAG	0.053	0.049	0.21	1	-0.26	6	7
HRAS	-0.001	0.013	-10000	0	-0.28	2	2
RAP1A	0	0	-10000	0	-10000	0	0
ARF5/GDP	-0.002	0.023	-10000	0	-0.3	1	1
PLCG2	-0.001	0.029	-10000	0	-0.55	2	2
PLCG1	0	0	-10000	0	-10000	0	0
ARF5	0	0.009	-10000	0	-10000	0	0
mol:GTP	0	0.019	0.27	2	-0.41	1	3
ARF1/GTP	0	0.019	0.28	2	-0.39	1	3
RHOA	0	0	-10000	0	-10000	0	0
YES1	-0.001	0.027	-10000	0	-0.82	1	1
RAP1A/GTP	0	0.019	-10000	0	-0.41	1	1
ADAP1	-0.002	0.031	-10000	0	-0.42	4	4
ARAP3	0	0.019	0.27	2	-0.41	1	3
INPPL1	0	0	-10000	0	-10000	0	0
PREX1	-0.011	0.058	-10000	0	-0.82	1	1
ARHGEF6	-0.009	0.086	-10000	0	-0.82	10	10
ARHGEF7	0	0	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
NRAS	-0.001	0.013	-10000	0	-0.28	2	2
FYN	-0.001	0.027	-10000	0	-0.82	1	1
ARF6	0	0	-10000	0	-10000	0	0
FGR	-0.001	0.029	-10000	0	-0.82	1	1
mol:Ca2+	0.039	0.028	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.001	0.018	-10000	0	-10000	0	0
ZAP70	-0.029	0.13	-10000	0	-0.82	19	19
mol:IP3	0.048	0.037	-10000	0	-10000	0	0
LYN	0	0	-10000	0	-10000	0	0
ARF1/GDP	-0.002	0.023	-10000	0	-0.3	1	1
RhoA/GDP	-0.001	0.02	0.28	2	-10000	0	2
PDK1/Src/Hsp90	0	0.006	-10000	0	-10000	0	0
BLNK	0	0	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.062	0.029	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-10000	0	0
PLEKHA2	0.03	0.005	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PTEN	-0.002	0.038	-10000	0	-0.8	2	2
HSP90AA1	0	0.009	-10000	0	-10000	0	0
ARF6/GTP	0	0.019	0.3	2	-10000	0	2
RhoA/GTP	0	0.018	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.01	0.057	-10000	0	-0.53	5	5
BLK	-0.039	0.1	-10000	0	-0.82	3	3
PDPK1	0	0	-10000	0	-10000	0	0
CYTH1	0	0.018	-10000	0	-10000	0	0
HCK	-0.004	0.032	-10000	0	-0.28	12	12
CYTH3	0	0.018	-10000	0	-0.38	1	1
CYTH2	0	0.018	-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	0.047	-10000	0	-0.55	6	6
SGK1	-0.003	0.047	-10000	0	-0.68	4	4
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.035	0.029	-10000	0	-0.29	2	2
SOS1	0	0	-10000	0	-10000	0	0
SYK	0	0.009	-10000	0	-0.28	1	1
ARF6/GDP	-0.001	0.02	0.29	2	-10000	0	2
mol:PI-3-4-5-P3	0	0.023	0.36	2	-0.41	1	3
ARAP3/RAP1A/GTP	0	0.019	-10000	0	-0.41	1	1
VAV1	-0.002	0.03	-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	-0.001	0.015	-10000	0	-0.41	1	1
PLEKHA1	0.029	0.02	-10000	0	-0.55	1	1
Rac1/GDP	-0.002	0.023	-10000	0	-0.3	1	1
LAT	-0.005	0.048	-10000	0	-0.82	2	2
Rac1/GTP	-0.004	0.041	-10000	0	-0.37	10	10
ITK	-0.017	0.081	-10000	0	-0.45	28	28
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.06	0.063	0.24	1	-0.38	6	7
LCK	-0.018	0.1	-10000	0	-0.43	39	39
BTK	-0.001	0.019	-10000	0	-0.38	1	1

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.029	0.042	-10000	0	-10000	0	0
regulation of axonogenesis	0.003	0.026	0.33	6	-10000	0	6
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	0.029	-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	0.047	-10000	0	-0.54	6	6
lamellipodium assembly	-0.004	0.03	-10000	0	-10000	0	0
MAPK3	0.021	0.023	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.009	0.029	-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	-0.003	0.023	-10000	0	-10000	0	0
ARF6	0.007	0.007	-10000	0	-10000	0	0
RAB11A	-0.001	0.013	-10000	0	-0.28	2	2
TIAM1	-0.001	0.018	-10000	0	-10000	0	0
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.021	0.023	-10000	0	-10000	0	0
actin filament bundle formation	0.006	0.02	-10000	0	-10000	0	0
KALRN	-0.01	0.067	-10000	0	-0.5	16	16
RAB11FIP3/RAB11A	0	0.008	-10000	0	-10000	0	0
RhoA/GDP	-0.006	0.02	-10000	0	-10000	0	0
NME1	-0.014	0.061	-10000	0	-10000	0	0
Rac1/GDP	-0.006	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	0.028	-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	0.012	0.052	-10000	0	-0.61	6	6
RAB11FIP3	0	0	-10000	0	-10000	0	0
tube morphogenesis	-0.004	0.03	-10000	0	-10000	0	0
ruffle organization	-0.003	0.026	-10000	0	-0.33	6	6
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	0.027	-10000	0	-0.33	6	6
mol:Phosphatidic acid	0.022	0.047	-10000	0	-0.54	6	6
Rac1/GTP	-0.004	0.03	-10000	0	-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	0.029	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.007	0.046	-9999	-0.44	6	6
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.001	0.014	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	-0.005	0.033	-9999	-0.5	2	2
lamellipodium assembly	0	0.017	-9999	-0.47	1	1
PIK3CA	0	0.009	-9999	-10000	0	0
PI3K	-0.001	0.022	-9999	-0.63	1	1
ARF6	0	0	-9999	-10000	0	0
TLN1	0	0	-9999	-10000	0	0
PXN	0.022	0	-9999	-10000	0	0
PIK3R1	-0.001	0.027	-9999	-0.82	1	1
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	-0.008	0.057	-9999	-0.33	23	23
ARF6/GDP	0	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.005	0.042	-9999	-0.47	7	7
p130Cas/Crk/Dock1	0	0	-9999	-10000	0	0
VCAM1	-0.008	0.075	-9999	-0.57	13	13
alpha4/beta1 Integrin/Paxillin/Talin	-0.001	0.01	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.001	0.012	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
mol:GDP	0.001	0.012	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GIT1	-0.001	0.018	-9999	-0.28	4	4
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.001	0.01	-9999	-10000	0	0
Rac1/GTP	0	0.019	-9999	-0.53	1	1

×

TCGA08_p53

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
CDKN2A	-0.021	0.073	-9999	-9999
TP53	-0.007	0.018	-9999	-9999
Senescence	-0.007	0.018	-9999	-9999
Apoptosis	-0.007	0.018	-9999	-9999
Activated_Oncogenes	0	0	-9999	-9999
MDM2	0.015	0.037	-9999	-9999
MDM4	0	0	-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	0.013	-9999	-0.39	1	1
MDM2/SUMO1	0	0.007	-9999	-10000	0	0
HDAC4	-0.001	0.027	-9999	-0.82	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	0.015	-9999	-0.46	1	1
SUMO1/HDAC1	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0	0.007	-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	0.018	-9999	-10000	0	0
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	0.005	-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	-0.001	0.013	-9999	-9999
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0.002	-9999	-9999
CD4	0	0	-9999	-9999
CLTA	0	0	-9999	-9999
mol:GTP	0.002	0	-9999	-9999
ARFGAP1	0.01	0.013	-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	0.005	-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	0.007	-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	0.007	-9999	-9999
ARFIP2	0	0	-9999	-9999
COPA	0	0	-9999	-9999
RAC1	0	0	-9999	-9999
ARF1/GTP/coatomer protein complex	0.025	0.002	-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	0.003	-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	0.001	-9999	-9999
PLD2	0	0	-9999	-9999
ARF-GAP1/v-SNARE	0.01	0.013	-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	0.01	0.013	-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
IKK alpha homodimer	0	0	-9999	-9999
FBXW11	0	0	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-9999
CHUK	0	0	-9999	-9999
NF kappa B2 p100/RelB	-0.001	0.008	-9999	-9999
NFKB1	0	0	-9999	-9999
MAP3K14	0	0	-9999	-9999
NF kappa B1 p50/RelB	-0.001	0.015	-9999	-9999
RELB	-0.002	0.024	-9999	-9999
NFKB2	0	0	-9999	-9999
NF kappa B2 p52/RelB	-0.001	0.013	-9999	-9999
regulation of B cell activation	-0.001	0.013	-9999	-9999

pid_entity	TCGA.LL.A441	TCGA.LL.A440	TCGA.JL.A3YX	TCGA.JL.A3YW
109_MAP3K5	0.042	0.053	0.053	0.053
47_PPARGC1A	0	0	0	0
105_BMP4	0	0	0	0
105_BMP6	0	0	0	0
105_BMP7	0	0	0	0
105_BMP2	0	0	0	0
131_RELN/VLDLR	0	0	0	-0.5
30_TGFB1/TGF beta receptor Type II	0	0	0	0
84_STAT5B	0.021	0.037	-0.077	0.059
84_STAT5A	0.021	0.037	-0.077	0.059