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	309
Signaling events mediated by Stem cell factor receptor (c-Kit)	297
Signaling mediated by p38-alpha and p38-beta	257
EGFR-dependent Endothelin signaling events	249
Reelin signaling pathway	245
HIF-1-alpha transcription factor network	200
p75(NTR)-mediated signaling	171
FOXM1 transcription factor network	171
Angiopoietin receptor Tie2-mediated signaling	165
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	163

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	0.2827	309	927	3	-0.22	-1000	1000	-1000	-0.026	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.2717	297	23216	78	-0.61	0.19	1000	-1000	-0.06	-1000
Signaling mediated by p38-alpha and p38-beta	0.2351	257	11314	44	-0.4	0	1000	-1000	-0.044	-1000
EGFR-dependent Endothelin signaling events	0.2278	249	5231	21	-0.33	0	1000	-1000	-0.059	-1000
Reelin signaling pathway	0.2242	245	13741	56	-0.47	0	1000	-1000	-0.086	-1000
HIF-1-alpha transcription factor network	0.1830	200	15246	76	-0.75	0.019	1000	-1000	-0.077	-1000
p75(NTR)-mediated signaling	0.1565	171	21392	125	-0.37	0	1000	-1000	-0.093	-1000
FOXM1 transcription factor network	0.1565	171	8757	51	-0.44	0.014	1000	-1000	-0.13	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1510	165	14567	88	-0.38	0.04	1000	-1000	-0.088	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1491	163	11088	68	-0.5	0.15	1000	-1000	-0.089	-1000
FOXA2 and FOXA3 transcription factor networks	0.1436	157	7258	46	-1.2	0.023	1000	-1000	-0.042	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1372	150	8125	54	-0.47	0.022	1000	-1000	-0.085	-1000
Glucocorticoid receptor regulatory network	0.1372	150	17130	114	-0.92	0.34	1000	-1000	-0.072	-1000
Arf6 signaling events	0.1263	138	8595	62	-0.33	0.017	1000	-1000	-0.058	-1000
Wnt signaling	0.1263	138	968	7	-0.17	-0.007	1000	-1000	-0.048	-1000
IL4-mediated signaling events	0.1217	133	12144	91	-0.98	0.51	1000	-1000	-0.14	-1000
Endothelins	0.1217	133	12824	96	-0.37	0.038	1000	-1000	-0.072	-1000
EPHB forward signaling	0.1217	133	11307	85	-0.3	0.16	1000	-1000	-0.08	-1000
Aurora B signaling	0.1208	132	8851	67	-0.31	0.009	1000	-1000	-0.065	-1000
ErbB2/ErbB3 signaling events	0.1171	128	8378	65	-0.38	0.018	1000	-1000	-0.061	-1000
Ephrin B reverse signaling	0.1125	123	5921	48	-0.3	0.17	1000	-1000	-0.064	-1000
IGF1 pathway	0.1116	122	6971	57	-0.18	0.08	1000	-1000	-0.085	-1000
Nongenotropic Androgen signaling	0.1016	111	5778	52	-0.23	0.11	1000	-1000	-0.054	-1000
Signaling events regulated by Ret tyrosine kinase	0.1006	110	9023	82	-0.17	0	1000	-1000	-0.076	-1000
ErbB4 signaling events	0.0997	109	7527	69	-0.41	0.056	1000	-1000	-0.073	-1000
Calcium signaling in the CD4+ TCR pathway	0.0997	109	3404	31	-0.32	0.012	1000	-1000	-0.075	-1000
BMP receptor signaling	0.0988	108	8761	81	-0.54	0.026	1000	-1000	-0.087	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0961	105	12683	120	-0.58	0.24	1000	-1000	-0.061	-1000
Plasma membrane estrogen receptor signaling	0.0924	101	8756	86	-0.19	0.094	1000	-1000	-0.072	-1000
Noncanonical Wnt signaling pathway	0.0915	100	2619	26	-0.17	0	1000	-1000	-0.071	-1000
Glypican 1 network	0.0897	98	4723	48	-0.32	0.032	1000	-1000	-0.041	-1000
IL23-mediated signaling events	0.0887	97	5871	60	-0.46	0.018	1000	-1000	-0.13	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0869	95	8137	85	-0.24	0.011	1000	-1000	-0.07	-1000
Syndecan-1-mediated signaling events	0.0851	93	3175	34	-0.22	0	1000	-1000	-0.066	-1000
Aurora C signaling	0.0842	92	644	7	-0.17	0	1000	-1000	-0.043	-1000
Visual signal transduction: Rods	0.0842	92	4794	52	-0.48	0	1000	-1000	-0.077	-1000
Signaling events mediated by PTP1B	0.0823	90	6843	76	-0.64	0.071	1000	-1000	-0.073	-1000
IL6-mediated signaling events	0.0805	88	6611	75	-0.28	0.05	1000	-1000	-0.075	-1000
amb2 Integrin signaling	0.0787	86	7108	82	-0.48	0	1000	-1000	-0.067	-1000
Integrins in angiogenesis	0.0778	85	7171	84	-0.33	0	1000	-1000	-0.094	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0686	75	2575	34	-0.096	0	1000	-1000	-0.064	-1000
Ephrin A reverse signaling	0.0677	74	522	7	-0.074	0	1000	-1000	-0.029	-1000
S1P1 pathway	0.0668	73	2658	36	-0.33	0.008	1000	-1000	-0.059	-1000
Signaling events mediated by PRL	0.0668	73	2515	34	-0.17	0.021	1000	-1000	-0.051	-1000
Syndecan-3-mediated signaling events	0.0659	72	2530	35	-0.34	0	1000	-1000	-0.062	-1000
PDGFR-alpha signaling pathway	0.0631	69	3037	44	-0.36	0.019	1000	-1000	-0.054	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0631	69	3612	52	-0.19	0.029	1000	-1000	-0.061	-1000
Signaling events mediated by the Hedgehog family	0.0622	68	3574	52	-0.22	0.032	1000	-1000	-0.071	-1000
TCGA08_rtk_signaling	0.0613	67	1760	26	-0.29	0.027	1000	-1000	-0.029	-1000
E-cadherin signaling in keratinocytes	0.0604	66	2850	43	-0.29	0.04	1000	-1000	-0.067	-1000
LPA receptor mediated events	0.0586	64	6564	102	-0.29	0.028	1000	-1000	-0.091	-1000
Ras signaling in the CD4+ TCR pathway	0.0576	63	1077	17	-0.12	-0.001	1000	-1000	-0.05	-1000
PLK1 signaling events	0.0531	58	4956	85	-0.22	0.029	1000	-1000	-0.049	-1000
Nectin adhesion pathway	0.0531	58	3676	63	-0.087	0.001	1000	-1000	-0.064	-1000
Visual signal transduction: Cones	0.0522	57	2198	38	-0.17	0.011	1000	-1000	-0.067	-1000
Fc-epsilon receptor I signaling in mast cells	0.0503	55	5378	97	-0.24	0.028	1000	-1000	-0.085	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0503	55	1815	33	-0.54	0	1000	-1000	-0.055	-1000
Rapid glucocorticoid signaling	0.0503	55	1104	20	-0.19	0.027	1000	-1000	-0.04	-1000
Presenilin action in Notch and Wnt signaling	0.0494	54	3336	61	-0.41	0.014	1000	-1000	-0.077	-1000
Signaling events mediated by HDAC Class III	0.0476	52	2081	40	-0.56	0.022	1000	-1000	-0.044	-1000
FAS signaling pathway (CD95)	0.0476	52	2479	47	-0.47	0.013	1000	-1000	-0.044	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0476	52	3865	74	-0.29	0.072	1000	-1000	-0.084	-1000
IL27-mediated signaling events	0.0467	51	2608	51	-0.29	0.035	1000	-1000	-0.066	-1000
LPA4-mediated signaling events	0.0448	49	589	12	-0.16	0.02	1000	-1000	-0.017	-1000
Effects of Botulinum toxin	0.0430	47	1242	26	-0.099	0.001	1000	-1000	-0.055	-1000
Canonical Wnt signaling pathway	0.0421	46	2362	51	-0.41	0.14	1000	-1000	-0.058	-1000
TCR signaling in naïve CD8+ T cells	0.0384	42	3965	93	-0.16	0.077	1000	-1000	-0.071	-1000
Coregulation of Androgen receptor activity	0.0375	41	3132	76	-0.17	0.034	1000	-1000	-0.049	-1000
Regulation of Androgen receptor activity	0.0375	41	2926	70	-0.25	0.021	1000	-1000	-0.064	-1000
IL12-mediated signaling events	0.0366	40	3504	87	-0.35	0.047	1000	-1000	-0.11	-1000
Insulin Pathway	0.0366	40	3029	74	-0.2	0.033	1000	-1000	-0.078	-1000
Regulation of Telomerase	0.0357	39	3997	102	-0.33	0.026	1000	-1000	-0.083	-1000
Syndecan-4-mediated signaling events	0.0357	39	2660	67	-0.32	0.005	1000	-1000	-0.09	-1000
Regulation of nuclear SMAD2/3 signaling	0.0329	36	4975	136	-0.3	0.052	1000	-1000	-0.06	-1000
Syndecan-2-mediated signaling events	0.0311	34	2390	69	-0.2	0.033	1000	-1000	-0.058	-1000
Regulation of p38-alpha and p38-beta	0.0311	34	1861	54	-0.35	0.029	1000	-1000	-0.066	-1000
TCGA08_retinoblastoma	0.0311	34	274	8	-0.052	0.01	1000	-1000	-0.024	-1000
Osteopontin-mediated events	0.0302	33	1284	38	-0.24	0.022	1000	-1000	-0.089	-1000
IL2 signaling events mediated by STAT5	0.0302	33	737	22	-0.11	0.063	1000	-1000	-0.037	-1000
Thromboxane A2 receptor signaling	0.0293	32	3445	105	-0.29	0.066	1000	-1000	-0.064	-1000
BCR signaling pathway	0.0293	32	3236	99	-0.13	0.042	1000	-1000	-0.079	-1000
Aurora A signaling	0.0265	29	1754	60	-0.21	0.006	1000	-1000	-0.058	-1000
Arf6 trafficking events	0.0256	28	2012	71	-0.44	0.032	1000	-1000	-0.065	-1000
TCGA08_p53	0.0238	26	188	7	-0.025	0.017	1000	-1000	-0.018	-1000
S1P5 pathway	0.0229	25	431	17	-0.045	0.024	1000	-1000	-0.048	-1000
BARD1 signaling events	0.0192	21	1245	57	-0.11	0.024	1000	-1000	-0.068	-1000
Glypican 2 network	0.0192	21	84	4	-0.038	-0.032	1000	-1000	-0.044	-1000
S1P4 pathway	0.0183	20	523	25	-0.045	0.008	1000	-1000	-0.048	-1000
Hedgehog signaling events mediated by Gli proteins	0.0174	19	1247	65	-0.067	0.044	1000	-1000	-0.071	-1000
Class I PI3K signaling events mediated by Akt	0.0174	19	1333	68	-0.25	0.053	1000	-1000	-0.065	-1000
Ceramide signaling pathway	0.0174	19	1495	76	-0.18	0.049	1000	-1000	-0.068	-1000
TRAIL signaling pathway	0.0174	19	947	48	-0.075	0.044	1000	-1000	-0.056	-1000
Retinoic acid receptors-mediated signaling	0.0174	19	1148	58	-0.1	0.037	1000	-1000	-0.069	-1000
Caspase cascade in apoptosis	0.0165	18	1347	74	-0.046	0.045	1000	-1000	-0.052	-1000
Signaling mediated by p38-gamma and p38-delta	0.0165	18	273	15	-0.018	0.022	1000	-1000	-0.046	-1000
Cellular roles of Anthrax toxin	0.0156	17	684	39	-0.14	0.019	1000	-1000	-0.029	-1000
IL2 signaling events mediated by PI3K	0.0156	17	1033	58	-0.044	0.06	1000	-1000	-0.071	-1000
E-cadherin signaling events	0.0156	17	87	5	-0.02	0	1000	-1000	-0.047	-1000
JNK signaling in the CD4+ TCR pathway	0.0146	16	280	17	-0.019	0.043	1000	-1000	-0.058	-1000
IL1-mediated signaling events	0.0137	15	963	62	-0.037	0.031	1000	-1000	-0.079	-1000
S1P3 pathway	0.0119	13	581	42	-0.033	0.021	1000	-1000	-0.053	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0110	12	357	28	-0.045	0.02	1000	-1000	-0.05	-1000
E-cadherin signaling in the nascent adherens junction	0.0110	12	939	76	-0.02	0.05	1000	-1000	-0.075	-1000
mTOR signaling pathway	0.0101	11	619	53	-0.021	0.025	1000	-1000	-0.061	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0101	11	411	37	-0.047	0.034	1000	-1000	-0.067	-1000
p38 MAPK signaling pathway	0.0101	11	516	44	-0.066	0.025	1000	-1000	-0.069	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0091	10	835	83	-0.038	0.053	1000	-1000	-0.078	-1000
Signaling events mediated by HDAC Class II	0.0082	9	704	75	-0.15	0	1000	-1000	-0.061	-1000
a4b1 and a4b7 Integrin signaling	0.0082	9	48	5	-0.009	-0.002	1000	-1000	-0.033	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0082	9	1141	125	-0.17	0.082	1000	-1000	-0.096	-1000
VEGFR1 specific signals	0.0082	9	529	56	-0.17	0.065	1000	-1000	-0.068	-1000
IFN-gamma pathway	0.0073	8	582	68	-0.066	0.075	1000	-1000	-0.08	-1000
HIF-2-alpha transcription factor network	0.0073	8	347	43	-0.17	0.18	1000	-1000	-0.07	-1000
Class I PI3K signaling events	0.0073	8	584	73	-0.044	0.059	1000	-1000	-0.063	-1000
EPO signaling pathway	0.0064	7	397	55	-0.036	0.058	1000	-1000	-0.086	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0064	7	359	45	-0.025	0.072	1000	-1000	-0.083	-1000
PDGFR-beta signaling pathway	0.0064	7	719	97	-0.026	0.05	1000	-1000	-0.08	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0055	6	149	23	-0.029	0.041	1000	-1000	-0.064	-1000
ceramide signaling pathway	0.0046	5	249	49	-0.027	0.054	1000	-1000	-0.046	-1000
FoxO family signaling	0.0046	5	375	64	-0.038	0.09	1000	-1000	-0.072	-1000
Atypical NF-kappaB pathway	0.0046	5	181	31	-0.02	0.03	1000	-1000	-0.066	-1000
Canonical NF-kappaB pathway	0.0037	4	160	39	-0.021	0.077	1000	-1000	-0.071	-1000
Signaling events mediated by HDAC Class I	0.0037	4	495	104	-0.095	0.046	1000	-1000	-0.072	-1000
Paxillin-dependent events mediated by a4b1	0.0037	4	144	36	-0.011	0.022	1000	-1000	-0.067	-1000
Circadian rhythm pathway	0.0027	3	87	22	-0.015	0.042	1000	-1000	-0.064	-1000
Arf6 downstream pathway	0.0027	3	142	43	-0.023	0.023	1000	-1000	-0.036	-1000
Insulin-mediated glucose transport	0.0027	3	101	32	-0.13	0.032	1000	-1000	-0.064	-1000
PLK2 and PLK4 events	0.0000	0	1	3	-0.012	0.013	1000	-1000	-0.028	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	9	27	-0.001	0.029	1000	-1000	-0.059	-1000
Arf1 pathway	0.0000	0	25	54	-0.001	0.025	1000	-1000	-0.037	-1000
Alternative NF-kappaB pathway	0.0000	0	11	13	-0.003	0	1000	-1000	-0.058	-1000
Total	NA	8343	488828	7203	-30	-990	131000	-131000	-8.5	-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	0.35	0.78	309	-10000	0	309
PI3K Class IB/PDE3B	-0.22	0.35	-10000	0	-0.79	309	309
PDE3B	-0.22	0.36	-10000	0	-0.79	309	309

×

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	-0.16	0.22	-10000	0	-0.39	499	499
CRKL	-0.17	0.23	-10000	0	-0.41	499	499
HRAS	-0.16	0.17	-10000	0	-0.45	65	65
mol:PIP3	-0.17	0.21	-10000	0	-0.4	501	501
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0	0	-10000	0	-10000	0	0
GAB1	-0.18	0.24	-10000	0	-0.44	500	500
FOXO3	-0.15	0.21	-10000	0	-0.37	498	498
AKT1	-0.16	0.22	-10000	0	-0.41	499	499
BAD	-0.15	0.21	-10000	0	-0.37	498	498
megakaryocyte differentiation	-0.18	0.23	-10000	0	-0.43	500	500
GSK3B	-0.15	0.21	-10000	0	-0.37	498	498
RAF1	-0.092	0.17	-10000	0	-0.39	44	44
SHC1	0	0	-10000	0	-10000	0	0
STAT3	-0.18	0.24	-10000	0	-0.44	500	500
STAT1	-0.45	0.56	-10000	0	-1	510	510
HRAS/SPRED1	-0.13	0.14	-10000	0	-0.36	65	65
cell proliferation	-0.18	0.24	-10000	0	-0.44	501	501
PIK3CA	0	0.009	-10000	0	-0.29	1	1
TEC	-0.002	0.041	-10000	0	-0.79	3	3
RPS6KB1	-0.18	0.24	-10000	0	-0.44	502	502
HRAS/SPRED2	-0.13	0.14	-10000	0	-0.39	44	44
LYN/TEC/p62DOK	-0.19	0.2	-10000	0	-0.4	500	500
MAPK3	-0.054	0.13	-10000	0	-0.31	22	22
STAP1	-0.2	0.24	-10000	0	-0.45	502	502
GRAP2	-0.014	0.1	-10000	0	-0.72	21	21
JAK2	-0.4	0.44	-10000	0	-0.87	510	510
STAT1 (dimer)	-0.44	0.54	-10000	0	-1	510	510
mol:Gleevec	0.006	0.009	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.19	0.2	-10000	0	-0.41	500	500
actin filament polymerization	-0.18	0.24	-10000	0	-0.44	500	500
LYN	0	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.27	0.33	-10000	0	-0.62	500	500
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
CBL/CRKL/GRB2	-0.17	0.18	-10000	0	-0.36	498	498
PI3K	-0.19	0.21	-10000	0	-0.41	505	505
PTEN	-0.001	0.034	-10000	0	-0.79	2	2
SCF/KIT/EPO/EPOR	-0.56	0.69	-10000	0	-1.3	498	498
MAPK8	-0.19	0.24	-10000	0	-0.45	501	501
STAT3 (dimer)	-0.18	0.23	-10000	0	-0.43	500	500
positive regulation of transcription	-0.041	0.11	-10000	0	-0.25	21	21
mol:GDP	-0.17	0.18	-10000	0	-0.36	489	489
PIK3C2B	-0.18	0.24	-10000	0	-0.44	500	500
CBL/CRKL	-0.15	0.22	-10000	0	-0.38	498	498
FER	-0.19	0.24	-10000	0	-0.44	505	505
SH2B3	-0.18	0.24	-10000	0	-0.44	500	500
PDPK1	-0.15	0.2	-10000	0	-0.36	501	501
SNAI2	-0.19	0.25	-10000	0	-0.45	502	502
positive regulation of cell proliferation	-0.32	0.4	-10000	0	-0.75	510	510
KITLG	0.002	0.067	-10000	0	-0.48	16	16
cell motility	-0.32	0.4	-10000	0	-0.75	510	510
PTPN6	0.015	0.021	-10000	0	-0.29	2	2
EPOR	-0.096	0.16	-10000	0	-10000	0	0
STAT5A (dimer)	-0.26	0.34	-10000	0	-0.62	512	512
SOCS1	-0.005	0.043	-10000	0	-0.32	18	18
cell migration	0.19	0.24	0.44	508	-10000	0	508
SOS1	0	0	-10000	0	-10000	0	0
EPO	-0.044	0.11	-10000	0	-0.3	177	177
VAV1	-0.003	0.043	-10000	0	-0.59	5	5
GRB10	-0.18	0.24	-10000	0	-0.44	500	500
PTPN11	0.013	0.013	-10000	0	-10000	0	0
SCF/KIT	-0.22	0.23	-10000	0	-0.46	512	512
GO:0007205	0.009	0.013	-10000	0	-10000	0	0
MAP2K1	-0.064	0.14	-10000	0	-0.35	22	22
CBL	0	0	-10000	0	-10000	0	0
KIT	-0.61	0.73	-10000	0	-1.4	496	496
MAP2K2	-0.064	0.14	-10000	0	-0.35	22	22
SHC/Grb2/SOS1	-0.19	0.2	-10000	0	-0.4	498	498
STAT5A	-0.27	0.35	-10000	0	-0.64	512	512
GRB2	0	0.009	-10000	0	-0.29	1	1
response to radiation	-0.18	0.24	-10000	0	-0.44	502	502
SHC/GRAP2	-0.01	0.077	-10000	0	-0.6	18	18
PTPRO	-0.18	0.24	-10000	0	-0.44	500	500
SH2B2	-0.19	0.24	-10000	0	-0.44	500	500
DOK1	-0.001	0.018	-10000	0	-0.29	4	4
MATK	-0.19	0.25	-10000	0	-0.45	508	508
CREBBP	0.02	0.018	-10000	0	-10000	0	0
BCL2	-0.13	0.3	-10000	0	-1.5	37	37

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.4	0.62	-9999	-1.3	370	370
MKNK1	0	0	-9999	-10000	0	0
MAPK14	-0.081	0.15	-9999	-0.29	369	369
ATF2/c-Jun	-0.052	0.15	-9999	-0.78	14	14
MAPK11	-0.083	0.16	-9999	-0.3	372	372
MITF	-0.092	0.2	-9999	-0.36	377	377
MAPKAPK5	-0.088	0.19	-9999	-0.35	372	372
KRT8	-0.095	0.2	-9999	-0.36	373	373
MAPKAPK3	0	0	-9999	-10000	0	0
MAPKAPK2	0	0.009	-9999	-0.29	1	1
p38alpha-beta/CK2	-0.12	0.23	-9999	-0.44	372	372
CEBPB	-0.088	0.19	-9999	-0.35	372	372
SLC9A1	-0.088	0.19	-9999	-0.35	372	372
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.082	0.19	-9999	-0.34	374	374
p38alpha-beta/MNK1	-0.12	0.17	-9999	-0.35	372	372
JUN	-0.051	0.15	-9999	-0.77	14	14
PPARGC1A	-0.21	0.36	-9999	-0.57	452	452
USF1	-0.088	0.19	-9999	-0.35	372	372
RAB5/GDP/GDI1	-0.085	0.12	-9999	-0.38	16	16
NOS2	-0.092	0.21	-9999	-0.82	18	18
DDIT3	-0.088	0.19	-9999	-0.35	372	372
RAB5A	0	0	-9999	-10000	0	0
HSPB1	-0.074	0.17	-9999	-0.43	56	56
p38alpha-beta/HBP1	-0.12	0.17	-9999	-0.35	372	372
CREB1	-0.093	0.2	-9999	-0.37	372	372
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.069	0.17	-9999	-0.49	16	16
RPS6KA4	-0.088	0.19	-9999	-0.35	372	372
PLA2G4A	-0.13	0.27	-9999	-0.72	141	141
GDI1	-0.088	0.19	-9999	-0.35	372	372
TP53	-0.11	0.23	-9999	-0.44	372	372
RPS6KA5	-0.095	0.2	-9999	-0.36	381	381
ESR1	-0.17	0.25	-9999	-0.42	506	506
HBP1	0	0	-9999	-10000	0	0
MEF2C	-0.09	0.2	-9999	-0.35	372	372
MEF2A	-0.089	0.19	-9999	-0.35	372	372
EIF4EBP1	-0.093	0.2	-9999	-0.37	372	372
KRT19	-0.1	0.21	-9999	-0.37	377	377
ELK4	-0.088	0.19	-9999	-0.35	372	372
ATF6	-0.088	0.19	-9999	-0.35	372	372
ATF1	-0.093	0.2	-9999	-0.37	372	372
p38alpha-beta/MAPKAPK2	-0.12	0.17	-9999	-0.35	372	372
p38alpha-beta/MAPKAPK3	-0.12	0.17	-9999	-0.52	19	19

×

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	-0.003	0.028	-9999	-0.29	10	10
EGFR	-0.29	0.38	-9999	-0.78	410	410
EGF/EGFR	-0.28	0.3	-9999	-0.53	563	563
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.25	0.26	-9999	-0.49	552	552
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.002	0.035	-9999	-0.62	3	3
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.15	0.31	-9999	-0.78	214	214
EGF/EGFR dimer/SHC	-0.29	0.3	-9999	-0.57	552	552
mol:GDP	-0.24	0.26	-9999	-0.48	552	552
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.059	0.21	-9999	-0.79	82	82
GRB2/SOS1	0	0.006	-9999	-10000	0	0
HRAS/GTP	-0.23	0.24	-9999	-0.45	552	552
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.23	0.24	-9999	-0.45	552	552
FRAP1	-0.24	0.25	-9999	-0.46	552	552
EGF/EGFR dimer	-0.33	0.35	-9999	-0.66	552	552
SOS1	0	0	-9999	-10000	0	0
GRB2	0	0.009	-9999	-0.29	1	1
ETA receptor/Endothelin-1	-0.046	0.16	-9999	-0.6	84	84

×

Reelin signaling pathway

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
CDK5R1/CDK5	-0.006	0.034	-9999	-10000	0	0
VLDLR	-0.025	0.14	-9999	-0.79	35	35
CRKL	0	0	-9999	-10000	0	0
LRPAP1	0	0	-9999	-10000	0	0
FYN	-0.001	0.034	-9999	-0.79	2	2
ITGA3	-0.004	0.05	-9999	-0.57	7	7
RELN/VLDLR/Fyn	-0.32	0.27	-9999	-0.54	660	660
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.005	0.046	-9999	-0.44	12	12
AKT1	-0.18	0.18	-9999	-0.36	230	230
MAP2K7	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
DAB1	-0.017	0.069	-9999	-0.29	65	65
RELN/LRP8/DAB1	-0.31	0.24	-9999	-0.5	652	652
LRPAP1/LRP8	-0.019	0.057	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.29	0.23	-9999	-0.47	652	652
DAB1/alpha3/beta1 Integrin	-0.27	0.22	-9999	-0.44	663	663
long-term memory	-0.35	0.29	-9999	-0.53	706	706
DAB1/LIS1	-0.28	0.23	-9999	-0.45	660	660
DAB1/CRLK/C3G	-0.27	0.22	-9999	-0.44	657	657
PIK3CA	0	0.009	-9999	-0.29	1	1
DAB1/NCK2	-0.28	0.23	-9999	-0.46	660	660
ARHGEF2	0	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.091	0.25	-9999	-0.74	135	135
CDK5R1	-0.008	0.049	-9999	-0.29	31	31
RELN	-0.47	0.39	-9999	-0.78	654	654
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
RELN/LRP8/Fyn	-0.32	0.26	-9999	-0.54	651	651
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.33	0.29	-9999	-0.53	672	672
MAPK8	-0.006	0.071	-9999	-0.79	9	9
RELN/VLDLR/DAB1	-0.31	0.25	-9999	-0.5	660	660
ITGB1	0	0	-9999	-10000	0	0
MAP1B	-0.3	0.25	-9999	-0.49	666	666
RELN/LRP8	-0.32	0.26	-9999	-0.53	651	651
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.31	0.25	-9999	-0.49	689	689
PI3K	-0.008	0.068	-9999	-0.6	14	14
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.003	0.037	-9999	-0.6	4	4
RAP1A	-0.25	0.2	-9999	-0.54	142	142
PAFAH1B1	0	0	-9999	-10000	0	0
MAPK8IP1	-0.004	0.046	-9999	-0.48	8	8
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.053	0.2	-9999	-0.77	75	75
NCK2	0	0	-9999	-10000	0	0
neuron differentiation	-0.12	0.13	-9999	-0.48	13	13
neuron adhesion	-0.23	0.19	-9999	-0.5	145	145
LRP8	-0.03	0.089	-9999	-10000	0	0
GSK3B	-0.17	0.18	-9999	-0.46	70	70
RELN/VLDLR/DAB1/Fyn	-0.29	0.24	-9999	-0.47	660	660
MAP3K11	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.21	0.18	-9999	-0.35	667	667
CDK5	-0.002	0.023	-9999	-0.29	7	7
MAPT	-0.045	0.24	-9999	-0.73	117	117
neuron migration	-0.22	0.23	-9999	-0.41	652	652
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.13	0.11	-9999	-0.48	13	13
RELN/VLDLR	-0.31	0.25	-9999	-0.5	660	660

×

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	-0.41	0.46	-9999	-1	273	273
HDAC7	0	0.002	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.32	0.31	-9999	-0.8	196	196
SMAD4	-0.001	0.024	-9999	-0.78	1	1
ID2	-0.41	0.46	-9999	-1	281	281
AP1	-0.18	0.28	-9999	-0.61	330	330
ABCG2	-0.43	0.5	-9999	-1.1	301	301
HIF1A	-0.051	0.064	-9999	-10000	0	0
TFF3	-0.48	0.52	-9999	-1.1	320	320
GATA2	-0.013	0.13	-9999	-0.63	41	41
AKT1	-0.052	0.08	-9999	-10000	0	0
response to hypoxia	-0.074	0.086	-9999	-0.24	43	43
MCL1	-0.41	0.46	-9999	-1	281	281
NDRG1	-0.41	0.46	-9999	-1	281	281
SERPINE1	-0.41	0.46	-9999	-1	271	271
FECH	-0.41	0.46	-9999	-1	275	275
FURIN	-0.41	0.46	-9999	-1	297	297
NCOA2	-0.03	0.17	-9999	-0.79	54	54
EP300	-0.051	0.12	-9999	-0.36	53	53
HMOX1	-0.41	0.46	-9999	-1	281	281
BHLHE40	-0.41	0.46	-9999	-1	280	280
BHLHE41	-0.41	0.47	-9999	-1	274	274
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.049	0.055	-9999	-0.6	1	1
ENG	-0.025	0.078	-9999	-0.54	1	1
JUN	0.003	0.064	-9999	-0.79	7	7
RORA	-0.41	0.46	-9999	-1	276	276
ABCB1	-0.34	0.55	-9999	-1.4	215	215
TFRC	-0.41	0.46	-9999	-1	297	297
CXCR4	-0.41	0.46	-9999	-1	264	264
TF	-0.64	0.57	-9999	-1.1	522	522
CITED2	-0.41	0.46	-9999	-1	265	265
HIF1A/ARNT	-0.48	0.53	-9999	-1.2	301	301
LDHA	-0.048	0.047	-9999	-10000	0	0
ETS1	-0.41	0.46	-9999	-1	297	297
PGK1	-0.41	0.46	-9999	-1	273	273
NOS2	-0.41	0.46	-9999	-1	298	298
ITGB2	-0.41	0.46	-9999	-1	297	297
ALDOA	-0.41	0.46	-9999	-1	299	299
Cbp/p300/CITED2	-0.42	0.44	-9999	-1.1	240	240
FOS	-0.23	0.37	-9999	-0.79	329	329
HK2	-0.41	0.46	-9999	-1	273	273
SP1	0.012	0.023	-9999	-10000	0	0
GCK	-0.13	0.36	-9999	-1.6	56	56
HK1	-0.41	0.46	-9999	-1	273	273
NPM1	-0.41	0.46	-9999	-1	264	264
EGLN1	-0.41	0.46	-9999	-1	297	297
CREB1	0.019	0	-9999	-10000	0	0
PGM1	-0.41	0.46	-9999	-1	280	280
SMAD3	0	0	-9999	-10000	0	0
EDN1	-0.19	0.4	-9999	-1.2	119	119
IGFBP1	-0.5	0.52	-9999	-1.1	363	363
VEGFA	-0.24	0.31	-9999	-0.77	102	102
HIF1A/JAB1	-0.028	0.026	-9999	-10000	0	0
CP	-0.52	0.55	-9999	-1.1	385	385
CXCL12	-0.43	0.5	-9999	-1.1	308	308
COPS5	0.009	0.006	-9999	-10000	0	0
SMAD3/SMAD4	-0.001	0.018	-9999	-0.6	1	1
BNIP3	-0.41	0.46	-9999	-1	297	297
EGLN3	-0.41	0.46	-9999	-1	291	291
CA9	-0.45	0.48	-9999	-1.1	297	297
TERT	-0.42	0.47	-9999	-1	299	299
ENO1	-0.41	0.46	-9999	-1	297	297
PFKL	-0.41	0.46	-9999	-0.99	297	297
NCOA1	0	0.024	-9999	-0.79	1	1
ADM	-0.44	0.49	-9999	-1.1	302	302
ARNT	-0.051	0.064	-9999	-10000	0	0
HNF4A	-0.002	0.046	-9999	-0.29	22	22
ADFP	-0.41	0.46	-9999	-1	301	301
SLC2A1	-0.24	0.32	-9999	-0.77	108	108
LEP	-0.75	0.52	-9999	-1.1	589	589
HIF1A/ARNT/Cbp/p300	-0.33	0.33	-9999	-0.8	236	236
EPO	-0.23	0.28	-9999	-0.85	54	54
CREBBP	-0.051	0.12	-9999	-0.36	52	52
HIF1A/ARNT/Cbp/p300/HDAC7	-0.31	0.31	-9999	-0.82	171	171
PFKFB3	-0.41	0.46	-9999	-1	299	299
NT5E	-0.41	0.47	-9999	-1	297	297

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.001	0.018	-10000	0	-0.6	1	1
Necdin/E2F1	-0.082	0.15	-10000	0	-0.68	43	43
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.14	0.21	-10000	0	-0.45	344	344
NGF (dimer)/p75(NTR)/BEX1	-0.25	0.31	-10000	0	-0.62	423	423
NT-4/5 (dimer)/p75(NTR)	-0.37	0.41	-10000	0	-0.75	541	541
IKBKB	-0.001	0.013	-10000	0	-0.29	2	2
AKT1	-0.14	0.22	-10000	0	-0.45	348	348
IKBKG	0	0	-10000	0	-10000	0	0
BDNF	-0.064	0.21	-10000	0	-0.66	105	105
MGDIs/NGR/p75(NTR)/LINGO1	-0.2	0.24	-10000	0	-0.55	334	334
FURIN	0	0.009	-10000	0	-0.29	1	1
proBDNF (dimer)/p75(NTR)/Sortilin	-0.2	0.28	-10000	0	-0.56	378	378
LINGO1	-0.07	0.12	-10000	0	-0.29	261	261
Sortilin/TRAF6/NRIF	-0.001	0.024	-10000	0	-0.78	1	1
proBDNF (dimer)	-0.064	0.21	-10000	0	-0.66	105	105
NTRK1	-0.011	0.07	-10000	0	-0.37	33	33
RTN4R	-0.011	0.056	-10000	0	-0.29	41	41
neuron apoptosis	-0.13	0.26	-10000	0	-0.47	378	378
IRAK1	-0.001	0.018	-10000	0	-0.29	4	4
SHC1	-0.15	0.26	-10000	0	-0.52	342	342
ARHGDIA	0	0	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.014	-10000	0	-0.44	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.15	0.23	-10000	0	-0.48	342	342
MAGEH1	-0.001	0.024	-10000	0	-0.79	1	1
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.17	0.26	-10000	0	-0.52	356	356
Mammalian IAPs/DIABLO	-0.005	0.044	-10000	0	-0.47	9	9
proNGF (dimer)	-0.014	0.097	-10000	0	-0.62	24	24
MAGED1	-0.001	0.018	-10000	0	-0.29	4	4
APP	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.27	0.37	-10000	0	-0.79	371	371
ZNF274	0	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.14	0.21	-10000	0	-0.45	342	342
NGF	-0.014	0.098	-10000	0	-0.62	24	24
cell cycle arrest	-0.11	0.23	-10000	0	-0.43	342	342
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.1	0.16	-10000	0	-0.33	342	342
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.33	0.36	-10000	0	-0.66	541	541
NCSTN	0	0	-10000	0	-10000	0	0
mol:GTP	-0.17	0.25	-10000	0	-0.54	342	342
PSENEN	-0.001	0.013	-10000	0	-10000	0	0
mol:ceramide	-0.13	0.24	-10000	0	-0.47	342	342
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.082	0.12	-10000	0	-0.48	13	13
p75(NTR)/beta APP	-0.18	0.28	-10000	0	-0.6	334	334
BEX1	-0.15	0.27	-10000	0	-0.51	317	317
mol:GDP	-0.16	0.26	-10000	0	-0.53	342	342
NGF (dimer)	-0.081	0.18	-10000	0	-0.48	172	172
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.18	0.22	-10000	0	-0.5	334	334
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
RAC1/GTP	-0.14	0.22	-10000	0	-0.46	342	342
MYD88	0	0	-10000	0	-10000	0	0
CHUK	0	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.17	0.26	-10000	0	-0.54	342	342
RHOB	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.059	0.087	-10000	0	-10000	0	0
NT3 (dimer)	-0.13	0.29	-10000	0	-0.75	185	185
TP53	-0.16	0.22	-10000	0	-0.45	378	378
PRDM4	-0.13	0.24	-10000	0	-0.48	342	342
BDNF (dimer)	-0.17	0.23	-10000	0	-0.56	226	226
PIK3CA	0	0.009	-10000	0	-0.29	1	1
SORT1	-0.001	0.024	-10000	0	-0.79	1	1
activation of caspase activity	-0.14	0.21	-10000	0	-0.44	344	344
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.15	0.23	-10000	0	-0.48	342	342
RHOC	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	-0.15	0.27	-10000	0	-0.49	349	349
DIABLO	0	0	-10000	0	-10000	0	0
SMPD2	-0.13	0.24	-10000	0	-0.48	342	342
APH1B	-0.001	0.024	-10000	0	-0.79	1	1
APH1A	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.17	0.25	-10000	0	-0.53	342	342
PSEN1	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.27	0.35	-10000	0	-0.68	434	434
MAPK8	-0.1	0.24	-10000	0	-0.43	334	334
MAPK9	-0.1	0.23	-10000	0	-0.43	334	334
APAF1	0	0	-10000	0	-10000	0	0
NTF3	-0.13	0.29	-10000	0	-0.75	185	185
NTF4	-0.27	0.37	-10000	0	-0.79	371	371
NDN	-0.031	0.15	-10000	0	-0.79	43	43
RAC1/GDP	0	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.14	0.2	-10000	0	-0.42	342	342
p75 CTF/Sortilin/TRAF6/NRIF	0	0.014	-10000	0	-0.47	1	1
RhoA-B-C/GTP	-0.17	0.25	-10000	0	-0.54	342	342
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.17	0.24	-10000	0	-0.48	378	378
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.18	0.26	-10000	0	-0.51	378	378
PRKACB	-0.016	0.077	-10000	0	-0.33	53	53
proBDNF (dimer)/p75 ECD	-0.048	0.16	-10000	0	-0.6	79	79
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.077	-10000	0	-0.5	21	21
BIRC2	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.12	0.25	0.24	75	-0.46	343	418
BAD	-0.11	0.24	-10000	0	-0.44	337	337
RIPK2	-0.001	0.02	-10000	0	-0.29	5	5
NGFR	-0.24	0.36	-10000	0	-0.79	334	334
CYCS	-0.14	0.21	-10000	0	-0.44	342	342
ADAM17	0	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.15	0.22	-10000	0	-0.48	342	342
BCL2L11	-0.11	0.24	-10000	0	-0.44	337	337
BDNF (dimer)/p75(NTR)	-0.23	0.32	-10000	0	-0.65	378	378
PI3K	-0.16	0.23	-10000	0	-0.49	348	348
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.15	0.23	-10000	0	-0.48	342	342
NDNL2	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
PRKCI	0	0.009	-10000	0	-0.29	1	1
NGF (dimer)/p75(NTR)	-0.19	0.29	-10000	0	-0.61	342	342
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.15	0.23	-10000	0	-0.48	342	342
TRAF6	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	-0.001	0.024	-10000	0	-0.79	1	1
PLG	-0.002	0.025	-10000	0	-0.29	8	8
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.18	0.26	-10000	0	-0.51	386	386
SQSTM1	0	0.009	-10000	0	-0.29	1	1
NGFRAP1	-0.002	0.041	-10000	0	-0.79	3	3
CASP3	-0.1	0.22	-10000	0	-0.41	337	337
E2F1	-0.092	0.14	-10000	0	-0.29	345	345
CASP9	0	0	-10000	0	-10000	0	0
IKK complex	-0.064	0.11	-10000	0	-0.56	22	22
NGF (dimer)/TRKA	-0.018	0.088	-10000	0	-0.6	21	21
MMP7	-0.12	0.28	-10000	0	-0.7	191	191
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.14	0.21	-10000	0	-0.45	342	342
MMP3	-0.12	0.16	-10000	0	-0.31	421	421
APAF-1/Caspase 9	-0.1	0.16	-10000	0	-0.59	20	20

×

FOXM1 transcription factor 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.24	0.44	-9999	-0.88	222	222
PLK1	-0.087	0.11	-9999	-10000	0	0
BIRC5	-0.1	0.1	-9999	-10000	0	0
HSPA1B	-0.24	0.44	-9999	-0.9	203	203
MAP2K1	0.008	0.03	-9999	-10000	0	0
BRCA2	-0.24	0.44	-9999	-0.94	181	181
FOXM1	-0.29	0.52	-9999	-0.98	289	289
XRCC1	-0.24	0.44	-9999	-0.89	213	213
FOXM1B/p19	-0.29	0.42	-9999	-0.89	271	271
Cyclin D1/CDK4	-0.22	0.41	-9999	-0.84	206	206
CDC2	-0.26	0.46	-9999	-0.86	289	289
TGFA	-0.22	0.42	-9999	-0.84	227	227
SKP2	-0.24	0.44	-9999	-0.91	195	195
CCNE1	-0.056	0.13	-9999	-0.3	223	223
CKS1B	-0.24	0.44	-9999	-0.9	209	209
RB1	-0.12	0.13	-9999	-0.9	1	1
FOXM1C/SP1	-0.3	0.45	-9999	-0.91	284	284
AURKB	-0.079	0.11	-9999	-10000	0	0
CENPF	-0.27	0.46	-9999	-0.91	247	247
CDK4	0.007	0.022	-9999	-0.3	4	4
MYC	-0.21	0.41	-9999	-0.82	228	228
CHEK2	0.008	0.033	-9999	-0.32	2	2
ONECUT1	-0.24	0.43	-9999	-0.86	229	229
CDKN2A	-0.038	0.11	-9999	-0.29	188	188
LAMA4	-0.24	0.44	-9999	-0.9	208	208
FOXM1B/HNF6	-0.27	0.49	-9999	-1	228	228
FOS	-0.44	0.67	-9999	-1.3	377	377
SP1	0	0	-9999	-10000	0	0
CDC25B	-0.24	0.44	-9999	-0.9	202	202
response to radiation	-0.007	0.03	-9999	-10000	0	0
CENPB	-0.24	0.44	-9999	-0.88	222	222
CENPA	-0.27	0.46	-9999	-0.95	213	213
NEK2	-0.29	0.45	-9999	-0.95	220	220
HIST1H2BA	-0.24	0.44	-9999	-0.9	209	209
CCNA2	-0.11	0.15	-9999	-0.3	427	427
EP300	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.28	0.49	-9999	-1	226	226
CCNB2	-0.27	0.46	-9999	-0.92	237	237
CCNB1	-0.26	0.46	-9999	-0.94	226	226
ETV5	-0.24	0.44	-9999	-0.9	202	202
ESR1	-0.34	0.58	-9999	-1.2	273	273
CCND1	-0.23	0.42	-9999	-0.85	219	219
GSK3A	0.014	0.021	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.081	0.14	-9999	-0.33	189	189
CDK2	0.006	0.009	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.01	0.036	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.33	0.38	-9999	-0.86	298	298
GAS1	-0.28	0.5	-9999	-1	223	223
MMP2	-0.24	0.44	-9999	-0.91	209	209
RB1/FOXM1C	-0.24	0.44	-9999	-0.88	238	238
CREBBP	0	0	-9999	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	-0.14	0.42	-10000	0	-0.91	248	248
NCK1/PAK1/Dok-R	-0.096	0.18	-10000	0	-0.42	248	248
NCK1/Dok-R	-0.26	0.48	-10000	0	-1.1	248	248
PIK3CA	0.003	0.011	-10000	0	-0.29	1	1
mol:beta2-estradiol	0.039	0.1	0.24	207	-10000	0	207
RELA	0	0	-10000	0	-10000	0	0
SHC1	0.008	0.006	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.04	0.11	0.25	203	-0.32	11	214
TNIP2	0	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.24	0.44	-10000	0	-1	248	248
FN1	-0.12	0.14	-10000	0	-0.29	431	431
PLD2	-0.21	0.54	-10000	0	-1.2	248	248
PTPN11	0	0	-10000	0	-10000	0	0
GRB14	-0.1	0.22	-10000	0	-0.48	231	231
ELK1	-0.17	0.48	-10000	0	-1	248	248
GRB7	-0.023	0.085	-10000	0	-0.31	79	79
PAK1	-0.007	0.044	-10000	0	-0.29	25	25
Tie2/Ang1/alpha5/beta1 Integrin	-0.22	0.5	-10000	0	-1.1	248	248
CDKN1A	-0.072	0.28	-10000	0	-0.59	206	206
ITGA5	0	0.009	-10000	0	-0.29	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.26	0.48	-10000	0	-1.1	248	248
CRK	0	0	-10000	0	-10000	0	0
mol:NO	-0.077	0.32	-10000	0	-0.66	248	248
PLG	-0.22	0.54	-10000	0	-1.2	248	248
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.19	0.38	-10000	0	-0.88	248	248
GRB2	0	0.009	-10000	0	-0.29	1	1
PIK3R1	-0.002	0.09	-10000	0	-0.79	14	14
ANGPT2	-0.12	0.28	-10000	0	-0.72	127	127
BMX	-0.38	0.6	-10000	0	-1.4	249	249
ANGPT1	-0.25	0.58	-10000	0	-1.4	218	218
tube development	-0.09	0.31	-10000	0	-0.64	248	248
ANGPT4	-0.24	0.36	-10000	0	-0.79	331	331
response to hypoxia	-0.011	0.031	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.3	0.55	-10000	0	-1.3	248	248
alpha5/beta1 Integrin	0	0.006	-10000	0	-10000	0	0
FGF2	-0.32	0.39	-10000	0	-0.79	446	446
STAT5A (dimer)	-0.11	0.36	-10000	0	-0.77	206	206
mol:L-citrulline	-0.077	0.32	-10000	0	-0.66	248	248
AGTR1	-0.2	0.34	-10000	0	-0.7	328	328
MAPK14	-0.2	0.52	-10000	0	-1.1	248	248
Tie2/SHP2	-0.11	0.3	-10000	0	-1.3	58	58
TEK	-0.11	0.34	-10000	0	-1.5	58	58
RPS6KB1	-0.13	0.41	-10000	0	-0.87	248	248
Angiotensin II/AT1	-0.15	0.26	-10000	0	-0.61	268	268
Tie2/Ang1/GRB2	-0.28	0.53	-10000	0	-1.2	248	248
MAPK3	-0.18	0.49	-10000	0	-1.1	248	248
MAPK1	-0.18	0.49	-10000	0	-1.1	248	248
Tie2/Ang1/GRB7	-0.27	0.53	-10000	0	-1.2	248	248
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.21	0.54	-10000	0	-1.2	248	248
PI3K	-0.17	0.48	-10000	0	-1.1	248	248
FES	-0.2	0.51	-10000	0	-1.1	248	248
Crk/Dok-R	-0.26	0.48	-10000	0	-1.1	248	248
Tie2/Ang1/ABIN2	-0.28	0.53	-10000	0	-1.2	248	248
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.11	0.38	-10000	0	-0.8	248	248
STAT5A	-0.004	0.067	-10000	0	-0.79	8	8
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.13	0.41	-10000	0	-0.87	248	248
Tie2/Ang2	-0.15	0.42	-10000	0	-0.9	226	226
Tie2/Ang1	-0.24	0.59	-10000	0	-1.3	248	248
FOXO1	-0.11	0.38	-10000	0	-0.81	249	249
ELF1	0.013	0.024	-10000	0	-10000	0	0
ELF2	-0.21	0.53	-10000	0	-1.2	248	248
mol:Choline	-0.2	0.51	-10000	0	-1.1	248	248
cell migration	-0.045	0.11	-10000	0	-0.24	208	208
FYN	-0.11	0.35	-10000	0	-0.73	247	247
DOK2	-0.003	0.045	-10000	0	-0.5	7	7
negative regulation of cell cycle	-0.061	0.26	-10000	0	-0.54	206	206
ETS1	-0.031	0.12	-10000	0	-0.96	6	6
PXN	-0.09	0.34	-10000	0	-0.71	248	248
ITGB1	0	0	-10000	0	-10000	0	0
NOS3	-0.097	0.36	-10000	0	-0.75	248	248
RAC1	0	0	-10000	0	-10000	0	0
TNF	-0.042	0.14	-10000	0	-0.5	38	38
MAPKKK cascade	-0.2	0.51	-10000	0	-1.1	248	248
RASA1	0	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.23	0.55	-10000	0	-1.2	248	248
NCK1	0	0	-10000	0	-10000	0	0
vasculogenesis	-0.063	0.29	-10000	0	-0.58	248	248
mol:Phosphatidic acid	-0.2	0.51	-10000	0	-1.1	248	248
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.077	0.32	-10000	0	-0.66	248	248
Rac1/GTP	-0.18	0.34	-10000	0	-0.81	248	248
MMP2	-0.21	0.54	-10000	0	-1.2	249	249

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.078	0.16	-10000	0	-0.39	153	153
NFATC2	-0.055	0.27	-10000	0	-0.76	127	127
NFATC3	-0.048	0.12	-10000	0	-0.28	95	95
CD40LG	-0.36	0.57	-10000	0	-1.1	343	343
ITCH	0.016	0.095	-10000	0	-10000	0	0
CBLB	0.016	0.095	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.25	0.36	-10000	0	-1.1	123	123
JUNB	-0.001	0.013	-10000	0	-0.29	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.034	0.1	-10000	0	-0.33	109	109
T cell anergy	-0.024	0.16	-10000	0	-0.48	109	109
TLE4	-0.031	0.26	-10000	0	-0.72	103	103
Jun/NFAT1-c-4/p21SNFT	-0.28	0.43	-10000	0	-0.91	308	308
AP-1/NFAT1-c-4	-0.5	0.65	-10000	0	-1.3	344	344
IKZF1	-0.019	0.21	-10000	0	-0.62	89	89
T-helper 2 cell differentiation	-0.11	0.3	-10000	0	-0.83	119	119
AP-1/NFAT1	-0.23	0.32	-10000	0	-0.64	375	375
CALM1	-0.018	0.053	-10000	0	-10000	0	0
EGR2	-0.27	0.63	-10000	0	-1.6	170	170
EGR3	-0.36	0.71	-10000	0	-1.5	299	299
NFAT1/FOXP3	-0.12	0.22	-10000	0	-0.56	147	147
EGR1	-0.24	0.37	-10000	0	-0.79	347	347
JUN	-0.001	0.066	-10000	0	-0.8	7	7
EGR4	-0.015	0.078	-10000	0	-0.29	80	80
mol:Ca2+	-0.021	0.061	-10000	0	-10000	0	0
GBP3	-0.023	0.22	-10000	0	-0.67	89	89
FOSL1	-0.009	0.061	-10000	0	-0.34	30	30
NFAT1-c-4/MAF/IRF4	-0.3	0.46	-10000	0	-0.94	321	321
DGKA	-0.018	0.21	-10000	0	-0.62	85	85
CREM	0	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.38	0.52	-10000	0	-1.1	343	343
CTLA4	-0.089	0.24	-10000	0	-0.61	109	109
NFAT1-c-4 (dimer)/EGR1	-0.42	0.56	-10000	0	-1.2	340	340
NFAT1-c-4 (dimer)/EGR4	-0.28	0.45	-10000	0	-0.9	330	330
FOS	-0.24	0.37	-10000	0	-0.8	329	329
IFNG	-0.15	0.27	-10000	0	-0.83	112	112
T cell activation	-0.17	0.35	-10000	0	-0.78	203	203
MAF	-0.001	0.024	-10000	0	-0.79	1	1
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.15	0.36	0.66	325	-10000	0	325
TNF	-0.3	0.51	-10000	0	-1	328	328
FASLG	-0.34	0.67	-10000	0	-1.3	329	329
TBX21	-0.022	0.15	-10000	0	-0.66	55	55
BATF3	-0.002	0.03	-10000	0	-0.39	5	5
PRKCQ	-0.023	0.16	-10000	0	-0.68	57	57
PTPN1	-0.019	0.21	-10000	0	-0.64	79	79
NFAT1-c-4/ICER1	-0.28	0.44	-10000	0	-0.9	328	328
GATA3	-0.035	0.15	-10000	0	-0.57	70	70
T-helper 1 cell differentiation	-0.15	0.26	-10000	0	-0.81	112	112
IL2RA	-0.24	0.34	-10000	0	-0.96	130	130
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.018	0.21	-10000	0	-0.61	91	91
E2F1	-0.078	0.14	-10000	0	-0.28	345	345
PPARG	-0.19	0.34	-10000	0	-0.79	268	268
SLC3A2	-0.018	0.21	-10000	0	-0.57	112	112
IRF4	-0.07	0.22	-10000	0	-0.73	106	106
PTGS2	-0.46	0.65	-10000	0	-1.2	417	417
CSF2	-0.35	0.55	-10000	0	-1.1	336	336
JunB/Fra1/NFAT1-c-4	-0.27	0.42	-10000	0	-0.88	314	314
IL4	-0.12	0.32	-10000	0	-0.88	117	117
IL5	-0.35	0.55	-10000	0	-1.1	334	334
IL2	-0.17	0.36	-10000	0	-0.8	199	199
IL3	-0.062	0.065	-10000	0	-10000	0	0
RNF128	-0.045	0.27	-10000	0	-0.85	109	109
NFATC1	-0.15	0.36	-10000	0	-0.67	324	324
CDK4	0.079	0.23	0.6	45	-10000	0	45
PTPRK	-0.023	0.23	-10000	0	-0.71	75	75
IL8	-0.35	0.56	-10000	0	-1.1	336	336
POU2F1	0.001	0.01	-10000	0	-0.29	1	1

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.24	0.28	-9999	-0.79	109	109
PCK1	-1	0.7	-9999	-1.6	667	667
HNF4A	-0.25	0.28	-9999	-0.87	70	70
KCNJ11	-0.27	0.31	-9999	-0.86	134	134
AKT1	-0.14	0.14	-9999	-0.39	35	35
response to starvation	-0.001	0.008	-9999	-10000	0	0
DLK1	-0.49	0.55	-9999	-1.2	358	358
NKX2-1	-0.054	0.15	-9999	-10000	0	0
ACADM	-0.24	0.28	-9999	-0.8	115	115
TAT	-1.2	0.68	-9999	-1.6	775	775
CEBPB	0.006	0.007	-9999	-10000	0	0
CEBPA	-0.002	0.076	-9999	-0.79	10	10
TTR	-0.45	0.28	-9999	-0.8	292	292
PKLR	-0.24	0.28	-9999	-0.8	107	107
APOA1	-0.3	0.3	-9999	-0.89	98	98
CPT1C	-0.24	0.28	-9999	-0.8	105	105
ALAS1	-0.14	0.15	-9999	-10000	0	0
TFRC	-0.45	0.26	-9999	-0.7	406	406
FOXF1	-0.003	0.053	-9999	-0.52	9	9
NF1	0.017	0.024	-9999	-0.78	1	1
HNF1A (dimer)	0.003	0.027	-9999	-0.3	8	8
CPT1A	-0.24	0.28	-9999	-0.79	109	109
HMGCS1	-0.24	0.28	-9999	-0.77	124	124
NR3C1	-0.11	0.13	-9999	-0.57	36	36
CPT1B	-0.24	0.28	-9999	-0.8	110	110
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.002	0.007	-9999	-10000	0	0
GCK	-0.28	0.35	-9999	-0.98	137	137
CREB1	-0.059	0.067	-9999	-10000	0	0
IGFBP1	-0.44	0.59	-9999	-1.5	244	244
PDX1	-0.13	0.15	-9999	-10000	0	0
UCP2	-0.24	0.28	-9999	-0.78	117	117
ALDOB	-0.26	0.3	-9999	-0.84	121	121
AFP	-0.68	0.6	-9999	-1.2	547	547
BDH1	-0.24	0.28	-9999	-0.8	109	109
HADH	-0.26	0.3	-9999	-0.85	106	106
F2	-0.29	0.3	-9999	-0.91	83	83
HNF1A	0.003	0.027	-9999	-0.3	8	8
G6PC	-0.2	0.12	-9999	-0.64	8	8
SLC2A2	-0.16	0.17	-9999	-10000	0	0
INS	0.023	0.066	-9999	-10000	0	0
FOXA1	-0.24	0.28	-9999	-0.57	315	315
FOXA3	-0.42	0.23	-9999	-0.55	730	730
FOXA2	-0.31	0.34	-9999	-0.86	180	180
ABCC8	-0.34	0.43	-9999	-1.2	170	170
ALB	-0.93	0.64	-9999	-1.4	705	705

×

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	-0.025	0.14	-9999	-0.79	35	35
LRPAP1	0	0	-9999	-10000	0	0
NUDC	0	0	-9999	-10000	0	0
RELN/LRP8	-0.32	0.26	-9999	-0.53	651	651
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0	0.009	-9999	-0.29	1	1
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.28	0.25	-9999	-0.48	651	651
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.017	0.069	-9999	-0.29	65	65
IQGAP1	0	0	-9999	-10000	0	0
PLA2G7	-0.015	0.091	-9999	-0.43	39	39
CALM1	0	0	-9999	-10000	0	0
DYNLT1	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.019	0.057	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0	0	-9999	-10000	0	0
CDK5R1	-0.008	0.049	-9999	-0.29	31	31
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.044	0.1	-9999	-10000	0	0
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.33	0.27	-9999	-0.55	660	660
YWHAE	0	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.23	0.19	-9999	-0.45	184	184
MAP1B	-0.008	0.054	-9999	-0.37	23	23
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.26	0.21	-9999	-0.42	651	651
RELN	-0.47	0.39	-9999	-0.78	654	654
PAFAH/LIS1	-0.009	0.056	-9999	-0.52	11	11
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.18	0.15	-9999	-0.4	25	25
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.2	0.18	-9999	-0.33	663	663
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.25	0.2	-9999	-0.41	651	651
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.022	0	-9999	-10000	0	0
PAFAH1B3	-0.035	0.095	-9999	-0.29	131	131
PAFAH1B2	-0.005	0.063	-9999	-0.79	7	7
MAP1B/LIS1/Dynein heavy chain	-0.005	0.034	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.22	0.18	-9999	-0.43	185	185
LRP8	-0.03	0.089	-9999	-10000	0	0
NDEL1/Katanin 60	-0.23	0.19	-9999	-0.45	185	185
P39/CDK5	-0.27	0.22	-9999	-0.44	651	651
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.26	0.24	-9999	-0.45	651	651
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	-0.28	0.24	-9999	-0.46	660	660
RELN/VLDLR	-0.31	0.25	-9999	-0.5	660	660
CDC42	0	0	-9999	-10000	0	0

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.024	0.079	0.37	1	-10000	0	1
SMARCC2	0.012	0.01	-10000	0	-10000	0	0
SMARCC1	0.012	0.01	-10000	0	-10000	0	0
TBX21	-0.13	0.25	-10000	0	-0.74	100	100
SUMO2	0	0.01	-10000	0	-0.29	1	1
STAT1 (dimer)	0.014	0.04	-10000	0	-0.29	19	19
FKBP4	-0.002	0.026	-10000	0	-0.29	9	9
FKBP5	-0.015	0.1	-10000	0	-0.68	24	24
GR alpha/HSP90/FKBP51/HSP90	0.11	0.14	0.34	60	-0.43	17	77
PRL	-0.086	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.26	0.3	0.55	445	-0.55	31	476
RELA	-0.039	0.083	-10000	0	-0.3	1	1
FGG	0.23	0.22	0.5	294	-0.52	2	296
GR beta/TIF2	0.1	0.2	0.35	114	-0.57	56	170
IFNG	-0.42	0.35	-10000	0	-0.76	483	483
apoptosis	-0.27	0.3	0.59	3	-0.65	303	306
CREB1	-0.009	0.031	-10000	0	-10000	0	0
histone acetylation	0.022	0.14	0.42	34	-0.42	26	60
BGLAP	-0.1	0.15	-10000	0	-0.53	17	17
GR/PKAc	0.11	0.12	0.34	53	-0.46	4	57
NF kappa B1 p50/RelA	-0.066	0.15	-10000	0	-0.43	31	31
SMARCD1	0.012	0.01	-10000	0	-10000	0	0
MDM2	0.12	0.1	0.25	270	-10000	0	270
GATA3	-0.026	0.16	-10000	0	-0.57	70	70
AKT1	0	0.004	-10000	0	-10000	0	0
CSF2	-0.039	0.11	-10000	0	-0.59	8	8
GSK3B	0	0.004	-10000	0	-10000	0	0
NR1I3	-0.21	0.26	0.56	3	-0.62	176	179
CSN2	0.19	0.18	0.44	135	-0.53	1	136
BRG1/BAF155/BAF170/BAF60A	-0.003	0.032	-10000	0	-0.46	5	5
NFATC1	0.001	0.042	-10000	0	-0.79	3	3
POU2F1	0.007	0.013	-10000	0	-0.29	1	1
CDKN1A	0.046	0.072	-10000	0	-1.5	2	2
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.007	0.008	-10000	0	-10000	0	0
SFN	-0.016	0.099	-10000	0	-0.5	36	36
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.1	0.14	0.34	45	-0.48	9	54
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.36	0.43	0.54	3	-0.88	397	400
JUN	-0.31	0.29	-10000	0	-0.6	449	449
IL4	-0.12	0.16	-10000	0	-0.53	34	34
CDK5R1	-0.008	0.05	-10000	0	-0.3	31	31
PRKACA	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.41	0.4	-10000	0	-0.73	587	587
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.11	0.13	0.34	48	-0.51	4	52
cortisol/GR alpha (monomer)	0.34	0.32	0.64	483	-0.66	1	484
NCOA2	-0.039	0.17	-10000	0	-0.79	54	54
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.28	0.38	-10000	0	-0.86	329	329
AP-1/NFAT1-c-4	-0.65	0.52	-10000	0	-1	666	666
AFP	-0.6	0.7	-10000	0	-1.5	366	366
SUV420H1	0	0	-10000	0	-10000	0	0
IRF1	0.19	0.16	0.47	95	-10000	0	95
TP53	0.032	0.023	-10000	0	-0.5	2	2
PPP5C	0	0	-10000	0	-10000	0	0
KRT17	-0.82	0.8	-10000	0	-1.6	503	503
KRT14	-0.81	0.77	-10000	0	-1.5	566	566
TBP	0.019	0.007	-10000	0	-10000	0	0
CREBBP	0.14	0.14	0.31	178	-10000	0	178
HDAC1	0	0.004	-10000	0	-10000	0	0
HDAC2	0.001	0.004	-10000	0	-10000	0	0
AP-1	-0.66	0.52	-10000	0	-1	667	667
MAPK14	0	0.003	-10000	0	-10000	0	0
MAPK10	-0.12	0.29	-10000	0	-0.79	171	171
MAPK11	-0.002	0.042	-10000	0	-0.8	3	3
KRT5	-0.92	0.81	-10000	0	-1.6	580	580
interleukin-1 receptor activity	-0.001	0.003	-10000	0	-10000	0	0
NCOA1	0.014	0.024	-10000	0	-0.78	1	1
STAT1	0.014	0.04	-10000	0	-0.29	19	19
CGA	-0.16	0.18	-10000	0	-0.53	77	77
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.2	0.18	0.38	474	-10000	0	474
MAPK3	0	0.003	-10000	0	-10000	0	0
MAPK1	0	0.003	-10000	0	-10000	0	0
ICAM1	-0.18	0.25	-10000	0	-0.57	219	219
NFKB1	-0.039	0.083	-10000	0	-10000	0	0
MAPK8	-0.23	0.22	-10000	0	-0.48	344	344
MAPK9	0	0.003	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.29	0.31	0.59	3	-0.69	303	306
BAX	0.048	0.032	-10000	0	-10000	0	0
POMC	-0.19	0.32	-10000	0	-1	76	76
EP300	0.14	0.14	0.29	341	-10000	0	341
cortisol/GR alpha (dimer)/p53	0.31	0.26	0.56	450	-0.56	1	451
proteasomal ubiquitin-dependent protein catabolic process	0.085	0.079	0.24	63	-10000	0	63
SGK1	0.22	0.21	-10000	0	-1.2	7	7
IL13	-0.31	0.28	-10000	0	-0.59	421	421
IL6	-0.49	0.62	-10000	0	-1.3	410	410
PRKACG	0	0	-10000	0	-10000	0	0
IL5	-0.27	0.23	-10000	0	-0.71	78	78
IL2	-0.41	0.35	-10000	0	-0.74	493	493
CDK5	-0.002	0.024	-10000	0	-0.3	7	7
PRKACB	-0.016	0.077	-10000	0	-0.33	53	53
HSP90AA1	0	0.009	-10000	0	-0.29	1	1
IL8	-0.2	0.3	-10000	0	-0.66	222	222
CDK5R1/CDK5	-0.007	0.036	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.055	0.1	-10000	0	-0.54	7	7
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.28	0.24	0.53	425	-0.49	2	427
SMARCA4	0.012	0.013	-10000	0	-0.29	1	1
chromatin remodeling	0.2	0.16	0.39	299	-0.66	1	300
NF kappa B1 p50/RelA/Cbp	0.06	0.17	0.35	52	-0.49	1	53
JUN (dimer)	-0.31	0.29	-10000	0	-0.6	451	451
YWHAH	0	0	-10000	0	-10000	0	0
VIPR1	-0.13	0.25	-10000	0	-0.62	143	143
NR3C1	0.2	0.2	0.46	268	-0.57	6	274
NR4A1	-0.063	0.24	-10000	0	-0.74	115	115
TIF2/SUV420H1	-0.03	0.13	-10000	0	-0.6	54	54
MAPKKK cascade	-0.27	0.3	0.59	3	-0.65	303	306
cortisol/GR alpha (dimer)/Src-1	0.3	0.26	0.55	464	-0.57	1	465
PBX1	0.005	0.037	-10000	0	-0.54	4	4
POU1F1	0.003	0.015	-10000	0	-0.29	2	2
SELE	-0.22	0.36	-10000	0	-1	119	119
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.2	0.16	0.39	297	-0.66	1	298
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.28	0.24	0.53	425	-0.49	2	427
mol:cortisol	0.19	0.2	0.37	512	-10000	0	512
MMP1	-0.22	0.11	-10000	0	-10000	0	0

×

Arf6 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
CENTA1/KIF3B	-0.004	0.043	-9999	-0.64	4	4
ARNO/beta Arrestin1-2	-0.12	0.18	-9999	-0.42	253	253
EGFR	-0.29	0.38	-9999	-0.78	410	410
EPHA2	-0.004	0.058	-9999	-0.79	6	6
USP6	0	0	-9999	-10000	0	0
IQSEC1	0	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.33	0.35	-9999	-0.66	552	552
ARRB2	-0.051	0.15	-9999	-0.44	148	148
mol:GTP	0.017	0.018	-9999	-0.16	4	4
ARRB1	-0.002	0.035	-9999	-0.79	2	2
FBXO8	0	0	-9999	-10000	0	0
TSHR	-0.037	0.16	-9999	-0.74	54	54
EGF	-0.15	0.31	-9999	-0.78	214	214
somatostatin receptor activity	0	0	-9999	-0.001	378	378
ARAP2	-0.004	0.058	-9999	-0.79	6	6
mol:GDP	-0.14	0.18	-9999	-0.35	351	351
mol:PI-3-4-5-P3	0	0	-9999	-0.001	292	292
ITGA2B	-0.018	0.078	-9999	-0.32	62	62
ARF6	0	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.036	-9999	-0.47	6	6
ADAP1	-0.005	0.05	-9999	-0.41	13	13
KIF13B	-0.001	0.034	-9999	-0.79	2	2
HGF/MET	-0.14	0.27	-9999	-0.64	240	240
PXN	0	0	-9999	-10000	0	0
ARF6/GTP	-0.13	0.15	-9999	-0.31	352	352
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.29	0.3	-9999	-0.57	552	552
ADRB2	-0.18	0.33	-9999	-0.79	253	253
receptor agonist activity	0	0	-9999	0	354	354
actin filament binding	0	0	-9999	-0.001	365	365
SRC	0	0.009	-9999	-0.29	1	1
ITGB3	-0.028	0.14	-9999	-0.79	37	37
GNAQ	-0.002	0.041	-9999	-0.79	3	3
EFA6/PI-4-5-P2	0	0.001	-9999	-0.001	331	331
ARF6/GDP	-0.014	0.083	-9999	-0.41	18	18
ARF6/GDP/GULP/ACAP1	-0.15	0.2	-9999	-0.51	190	190
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.025	0.094	-9999	-0.48	40	40
ACAP1	-0.02	0.095	-9999	-0.38	57	57
ACAP2	0	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.088	0.22	-9999	-0.65	148	148
EFNA1	0	0.009	-9999	-0.29	1	1
HGF	-0.053	0.2	-9999	-0.79	73	73
CYTH3	0.01	0.027	-9999	-0.61	2	2
CYTH2	0.006	0.002	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	287	287
endosomal lumen acidification	0	0	-9999	-0.001	299	299
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.053	0.2	-9999	-0.79	73	73
GNAQ/ARNO	0.004	0.025	-9999	-0.45	3	3
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	360	360
MET	-0.14	0.3	-9999	-0.78	189	189
GNA14	-0.013	0.084	-9999	-0.46	30	30
GNA15	-0.003	0.033	-9999	-0.36	8	8
GIT1	-0.001	0.02	-9999	-0.29	5	5
mol:PI-4-5-P2	0	0	-9999	-0.001	347	347
GNA11	-0.003	0.048	-9999	-0.79	4	4
LHCGR	-0.11	0.27	-9999	-0.79	148	148
AGTR1	-0.21	0.34	-9999	-0.7	328	328
desensitization of G-protein coupled receptor protein signaling pathway	-0.088	0.22	-9999	-0.65	148	148
IPCEF1/ARNO	-0.23	0.24	-9999	-0.46	552	552
alphaIIb/beta3 Integrin	-0.033	0.12	-9999	-0.62	40	40

×

Wnt 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.16	0.25	-9999	-0.44	385	385
FZD6	-0.007	0.075	-9999	-0.79	10	10
WNT6	-0.16	0.31	-9999	-0.69	255	255
WNT4	-0.021	0.12	-9999	-0.55	43	43
FZD3	-0.011	0.092	-9999	-0.79	15	15
WNT5A	-0.016	0.1	-9999	-0.79	18	18
WNT11	-0.17	0.32	-9999	-0.76	242	242

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.45	0.46	-10000	0	-1.1	232	232
STAT6 (cleaved dimer)	-0.5	0.45	-10000	0	-1	387	387
IGHG1	-0.16	0.16	-10000	0	-0.36	83	83
IGHG3	-0.45	0.44	-10000	0	-0.98	340	340
AKT1	-0.2	0.24	-10000	0	-0.65	92	92
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.15	0.2	-10000	0	-0.61	53	53
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.22	0.24	-10000	0	-0.65	105	105
THY1	-0.45	0.46	-10000	0	-1.1	243	243
MYB	-0.017	0.11	-10000	0	-0.79	23	23
HMGA1	-0.014	0.063	-10000	0	-0.29	53	53
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.28	0.29	-10000	0	-0.67	233	233
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.21	0.23	-10000	0	-0.61	78	78
SP1	0.018	0.006	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.024	0.028	-10000	0	-0.76	1	1
STAT6 (dimer)/ETS1	-0.48	0.44	-10000	0	-1	341	341
SOCS1	-0.29	0.31	-10000	0	-0.74	208	208
SOCS3	-0.22	0.26	-10000	0	-0.81	68	68
FCER2	-0.58	0.64	-10000	0	-1.4	373	373
PARP14	0.004	0.018	-10000	0	-10000	0	0
CCL17	-0.46	0.46	-10000	0	-1.1	261	261
GRB2	0	0.009	-10000	0	-0.29	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.16	0.19	-10000	0	-0.6	25	25
T cell proliferation	-0.45	0.48	-10000	0	-1.1	261	261
IL4R/JAK1	-0.45	0.46	-10000	0	-1.1	250	250
EGR2	-0.58	0.62	-10000	0	-1.4	336	336
JAK2	-0.008	0.035	-10000	0	-0.81	1	1
JAK3	0.01	0.035	-10000	0	-0.29	14	14
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
JAK1	0.004	0.026	-10000	0	-0.78	1	1
COL1A2	-0.14	0.16	-10000	0	-1.6	3	3
CCL26	-0.46	0.46	-10000	0	-1.1	230	230
IL4R	-0.48	0.49	-10000	0	-1.2	251	251
PTPN6	0.022	0.018	-10000	0	-0.28	2	2
IL13RA2	-0.46	0.46	-10000	0	-1.2	219	219
IL13RA1	-0.007	0.025	-10000	0	-10000	0	0
IRF4	-0.22	0.48	-10000	0	-1.5	114	114
ARG1	-0.11	0.12	-10000	0	-10000	0	0
CBL	-0.26	0.28	-10000	0	-0.65	204	204
GTF3A	0.013	0.015	-10000	0	-0.29	2	2
PIK3CA	0	0.009	-10000	0	-0.29	1	1
IL13RA1/JAK2	-0.013	0.041	-10000	0	-0.61	1	1
IRF4/BCL6	-0.2	0.42	-10000	0	-1.4	116	116
CD40LG	-0.031	0.18	-10000	0	-0.71	67	67
MAPK14	-0.25	0.28	-10000	0	-0.67	177	177
mitosis	-0.2	0.23	-10000	0	-0.62	92	92
STAT6	-0.52	0.54	-10000	0	-1.2	315	315
SPI1	0.007	0.024	-10000	0	-0.29	6	6
RPS6KB1	-0.18	0.22	-10000	0	-0.61	77	77
STAT6 (dimer)	-0.52	0.54	-10000	0	-1.2	315	315
STAT6 (dimer)/PARP14	-0.5	0.51	-10000	0	-1.1	345	345
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	-0.63	80	80
FRAP1	-0.2	0.24	-10000	0	-0.65	92	92
LTA	-0.46	0.46	-10000	0	-1.1	240	240
FES	-0.002	0.041	-10000	0	-0.79	3	3
T-helper 1 cell differentiation	0.51	0.52	1.2	316	-10000	0	316
CCL11	-0.48	0.44	-10000	0	-1.1	284	284
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.2	0.23	-10000	0	-0.64	80	80
IL2RG	-0.004	0.088	-10000	0	-0.36	53	53
IL10	-0.46	0.46	-10000	0	-1.1	236	236
IRS1	-0.032	0.16	-10000	0	-0.79	45	45
IRS2	-0.033	0.16	-10000	0	-0.79	46	46
IL4	-0.11	0.11	-10000	0	-10000	0	0
IL5	-0.46	0.46	-10000	0	-1.2	218	218
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.37	0.36	-10000	0	-0.82	299	299
COL1A1	-0.18	0.17	-10000	0	-1.7	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.46	0.47	-10000	0	-1.2	209	209
IL2R gamma/JAK3	-0.011	0.071	-10000	0	-0.45	20	20
TFF3	-0.56	0.58	-10000	0	-1.4	291	291
ALOX15	-0.53	0.57	-10000	0	-1.4	269	269
MYBL1	-0.042	0.1	-10000	0	-0.29	155	155
T-helper 2 cell differentiation	-0.39	0.38	-10000	0	-0.86	312	312
SHC1	0	0	-10000	0	-10000	0	0
CEBPB	0.009	0.009	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.21	0.23	-10000	0	-0.62	98	98
mol:PI-3-4-5-P3	-0.2	0.24	-10000	0	-0.65	92	92
PI3K	-0.21	0.25	-10000	0	-0.69	92	92
DOK2	-0.003	0.045	-10000	0	-0.5	7	7
ETS1	0.018	0.058	-10000	0	-0.75	6	6
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.15	0.18	-10000	0	-0.67	15	15
ITGB3	-0.48	0.5	-10000	0	-1.2	227	227
PIGR	-0.98	0.75	-10000	0	-1.5	682	682
IGHE	0.045	0.04	-10000	0	-10000	0	0
MAPKKK cascade	-0.15	0.18	-10000	0	-0.65	15	15
BCL6	0.001	0.059	-10000	0	-0.78	6	6
OPRM1	-0.46	0.46	-10000	0	-1.1	249	249
RETNLB	-0.46	0.46	-10000	0	-1.2	225	225
SELP	-0.62	0.68	-10000	0	-1.6	314	314
AICDA	-0.44	0.44	-10000	0	-1.1	253	253

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.01	0.2	-9999	-0.6	89	89
PTK2B	0.006	0.006	-9999	-10000	0	0
mol:Ca2+	0.021	0.2	-9999	-0.97	33	33
EDN1	-0.035	0.24	-9999	-0.82	83	83
EDN3	-0.37	0.39	-9999	-0.78	511	511
EDN2	-0.076	0.14	-9999	-0.31	269	269
HRAS/GDP	-0.03	0.21	-9999	-0.54	103	103
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.003	0.14	-9999	-0.48	48	48
ADCY4	-0.14	0.29	-9999	-0.55	313	313
ADCY5	-0.27	0.36	-9999	-0.6	515	515
ADCY6	-0.13	0.27	-9999	-0.52	294	294
ADCY7	-0.13	0.27	-9999	-0.52	294	294
ADCY1	-0.15	0.29	-9999	-0.56	309	309
ADCY2	-0.17	0.32	-9999	-0.59	327	327
ADCY3	-0.13	0.27	-9999	-0.52	294	294
ADCY8	-0.14	0.27	-9999	-0.53	294	294
ADCY9	-0.13	0.27	-9999	-0.52	294	294
arachidonic acid secretion	-0.11	0.3	-9999	-0.56	230	230
ETB receptor/Endothelin-1/Gq/GTP	-0.034	0.18	-9999	-0.4	158	158
GNAO1	-0.03	0.13	-9999	-0.48	67	67
HRAS	0.003	0.029	-9999	-0.29	10	10
ETA receptor/Endothelin-1/G12/GTP	0.038	0.21	-9999	-0.56	89	89
ETA receptor/Endothelin-1/Gs/GTP	-0.087	0.32	-9999	-0.56	294	294
mol:GTP	-0.001	0.006	-9999	-10000	0	0
COL3A1	-0.019	0.21	-9999	-0.6	89	89
EDNRB	-0.074	0.24	-9999	-0.79	114	114
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.025	0.25	-9999	-0.69	107	107
CYSLTR1	-0.021	0.24	-9999	-0.67	102	102
SLC9A1	0.002	0.1	-9999	-0.3	88	88
mol:GDP	-0.038	0.22	-9999	-0.57	108	108
SLC9A3	-0.053	0.28	-9999	-0.66	162	162
RAF1	-0.085	0.25	-9999	-0.54	167	167
JUN	0.027	0.18	-9999	-0.85	30	30
JAK2	-0.01	0.2	-9999	-0.6	89	89
mol:IP3	-0.03	0.18	-9999	-0.53	74	74
ETA receptor/Endothelin-1	0.035	0.25	-9999	-0.69	89	89
PLCB1	-0.052	0.21	-9999	-0.79	82	82
PLCB2	0.007	0.026	-9999	-0.54	2	2
ETA receptor/Endothelin-3	-0.27	0.31	-9999	-0.6	510	510
FOS	-0.25	0.5	-9999	-0.98	336	336
Gai/GDP	-0.016	0.16	-9999	-0.76	30	30
CRK	0.006	0.006	-9999	-10000	0	0
mol:Ca ++	-0.051	0.25	-9999	-0.67	116	116
BCAR1	0.005	0.006	-9999	-10000	0	0
PRKCB1	-0.032	0.17	-9999	-0.48	88	88
GNAQ	0.008	0.043	-9999	-0.79	3	3
GNAZ	-0.007	0.075	-9999	-0.79	10	10
GNAL	-0.19	0.33	-9999	-0.79	258	258
Gs family/GDP	-0.17	0.26	-9999	-0.58	258	258
ETA receptor/Endothelin-1/Gq/GTP	0.017	0.13	-9999	-0.43	50	50
MAPK14	-0.032	0.17	-9999	-0.49	89	89
TRPC6	0.018	0.22	-9999	-1.1	33	33
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GNAI1	-0.045	0.18	-9999	-0.79	62	62
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.041	0.18	-9999	-0.47	117	117
ETB receptor/Endothelin-2	-0.11	0.21	-9999	-0.65	121	121
ETB receptor/Endothelin-3	-0.34	0.34	-9999	-0.65	568	568
ETB receptor/Endothelin-1	-0.082	0.27	-9999	-0.66	183	183
MAPK3	-0.2	0.41	-9999	-0.79	339	339
MAPK1	-0.2	0.41	-9999	-0.79	339	339
Rac1/GDP	-0.028	0.2	-9999	-0.53	102	102
cAMP biosynthetic process	-0.18	0.3	-9999	-0.6	302	302
MAPK8	0.019	0.2	-9999	-0.79	40	40
SRC	0	0.009	-9999	-0.29	1	1
ETB receptor/Endothelin-1/Gi/GTP	-0.05	0.18	-9999	-0.53	89	89
p130Cas/CRK/Src/PYK2	-0.015	0.22	-9999	-0.64	74	74
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.028	0.2	-9999	-0.53	102	102
COL1A2	-0.056	0.26	-9999	-0.7	105	105
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.03	0.12	-9999	-0.45	24	24
mol:DAG	-0.03	0.18	-9999	-0.53	74	74
MAP2K2	-0.13	0.32	-9999	-0.57	345	345
MAP2K1	-0.13	0.32	-9999	-0.57	345	345
EDNRA	0.025	0.08	-9999	-0.49	8	8
positive regulation of muscle contraction	-0.011	0.17	-9999	-0.52	89	89
Gq family/GDP	-0.074	0.16	-9999	-0.61	62	62
HRAS/GTP	-0.053	0.21	-9999	-0.49	136	136
PRKCH	-0.024	0.17	-9999	-0.56	58	58
RAC1	0	0	-9999	-10000	0	0
PRKCA	-0.036	0.2	-9999	-0.58	87	87
PRKCB	-0.035	0.2	-9999	-0.57	80	80
PRKCE	-0.024	0.17	-9999	-0.57	54	54
PRKCD	-0.025	0.17	-9999	-0.58	54	54
PRKCG	-0.034	0.18	-9999	-0.52	74	74
regulation of vascular smooth muscle contraction	-0.3	0.57	-9999	-1.1	336	336
PRKCQ	-0.045	0.21	-9999	-0.62	91	91
PLA2G4A	-0.12	0.33	-9999	-0.63	230	230
GNA14	-0.003	0.086	-9999	-0.46	30	30
GNA15	0.007	0.035	-9999	-0.36	8	8
GNA12	0	0	-9999	-10000	0	0
GNA11	0.006	0.049	-9999	-0.79	4	4
Rac1/GTP	0.038	0.21	-9999	-0.56	89	89
MMP1	-0.12	0.13	-9999	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.052	0.15	-10000	0	-0.52	103	103
cell-cell adhesion	0.16	0.21	0.67	79	-10000	0	79
Ephrin B/EPHB2/RasGAP	-0.041	0.13	-10000	0	-0.44	96	96
ITSN1	-0.001	0.034	-10000	0	-0.79	2	2
PIK3CA	0	0.009	-10000	0	-0.29	1	1
SHC1	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.002	0.018	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.2	0.26	-10000	0	-0.52	423	423
HRAS/GDP	-0.17	0.22	-10000	0	-0.64	104	104
Ephrin B/EPHB1/GRB7	-0.22	0.28	-10000	0	-0.52	448	448
Endophilin/SYNJ1	-0.038	0.12	-10000	0	-0.41	96	96
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
Ephrin B/EPHB1/Src	-0.21	0.27	-10000	0	-0.51	446	446
endothelial cell migration	-0.006	0.054	-10000	0	-0.47	14	14
GRB2	0	0.009	-10000	0	-0.29	1	1
GRB7	-0.023	0.085	-10000	0	-0.31	79	79
PAK1	-0.047	0.14	-10000	0	-0.46	105	105
HRAS	-0.003	0.028	-10000	0	-0.29	10	10
RRAS	-0.039	0.12	-10000	0	-0.42	96	96
DNM1	-0.005	0.063	-10000	0	-0.73	8	8
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.2	0.26	-10000	0	-0.48	446	446
lamellipodium assembly	-0.16	0.21	-10000	0	-0.67	79	79
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.15	0.19	-10000	0	-0.36	424	424
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
EPHB2	-0.005	0.038	-10000	0	-0.29	19	19
EPHB3	-0.004	0.035	-10000	0	-0.29	16	16
EPHB1	-0.3	0.38	-10000	0	-0.79	424	424
EPHB4	0	0.009	-10000	0	-0.29	1	1
mol:GDP	-0.15	0.21	-10000	0	-0.64	97	97
Ephrin B/EPHB2	-0.041	0.13	-10000	0	-0.45	96	96
Ephrin B/EPHB3	-0.041	0.13	-10000	0	-0.45	96	96
JNK cascade	-0.17	0.21	-10000	0	-0.43	423	423
Ephrin B/EPHB1	-0.21	0.28	-10000	0	-0.52	446	446
RAP1/GDP	-0.13	0.18	-10000	0	-0.55	95	95
EFNB2	-0.001	0.024	-10000	0	-0.79	1	1
EFNB3	-0.069	0.22	-10000	0	-0.79	96	96
EFNB1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.19	0.23	-10000	0	-0.48	424	424
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.17	0.23	-10000	0	-0.67	100	100
Rap1/GTP	-0.17	0.22	-10000	0	-0.69	78	78
axon guidance	-0.052	0.15	-10000	0	-0.52	103	103
MAPK3	-0.095	0.19	-10000	0	-0.52	75	75
MAPK1	-0.095	0.19	-10000	0	-0.52	75	75
Rac1/GDP	-0.14	0.19	-10000	0	-0.58	95	95
actin cytoskeleton reorganization	-0.13	0.16	-10000	0	-0.51	85	85
CDC42/GDP	-0.14	0.19	-10000	0	-0.57	96	96
PI3K	-0.006	0.055	-10000	0	-0.48	14	14
EFNA5	-0.074	0.23	-10000	0	-0.78	104	104
Ephrin B2/EPHB4	-0.001	0.017	-10000	0	-0.52	1	1
Ephrin B/EPHB2/Intersectin/N-WASP	-0.03	0.099	-10000	0	-0.34	96	96
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.16	0.21	-10000	0	-0.66	83	83
PTK2	0.04	0.05	-10000	0	-10000	0	0
MAP4K4	-0.17	0.21	-10000	0	-0.43	423	423
SRC	0	0.009	-10000	0	-0.29	1	1
KALRN	-0.014	0.11	-10000	0	-0.79	20	20
Intersectin/N-WASP	-0.001	0.026	-10000	0	-0.6	2	2
neuron projection morphogenesis	-0.13	0.17	-10000	0	-0.54	84	84
MAP2K1	-0.11	0.2	-10000	0	-0.34	424	424
WASL	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.18	0.23	-10000	0	-0.47	423	423
cell migration	-0.12	0.22	-10000	0	-0.37	424	424
NRAS	-0.001	0.013	-10000	0	-0.29	2	2
SYNJ1	-0.039	0.12	-10000	0	-0.42	96	96
PXN	0	0	-10000	0	-10000	0	0
TF	-0.24	0.26	-10000	0	-0.45	624	624
HRAS/GTP	-0.18	0.23	-10000	0	-0.44	446	446
Ephrin B1/EPHB1-2	-0.19	0.23	-10000	0	-0.48	423	423
cell adhesion mediated by integrin	0.01	0.13	0.42	96	-10000	0	96
RAC1	0	0	-10000	0	-10000	0	0
mol:GTP	-0.19	0.25	-10000	0	-0.47	446	446
RAC1-CDC42/GTP	-0.16	0.21	-10000	0	-0.68	80	80
RASA1	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.13	0.18	-10000	0	-0.55	95	95
ruffle organization	-0.17	0.22	-10000	0	-0.69	79	79
NCK1	0	0	-10000	0	-10000	0	0
receptor internalization	0.002	0.14	-10000	0	-0.42	98	98
Ephrin B/EPHB2/KALRN	-0.049	0.15	-10000	0	-0.49	105	105
ROCK1	0.022	0.024	-10000	0	-0.48	1	1
RAS family/GDP	-0.11	0.15	-10000	0	-0.52	75	75
Rac1/GTP	-0.18	0.23	-10000	0	-0.73	79	79
Ephrin B/EPHB1/Src/Paxillin	-0.15	0.2	-10000	0	-0.37	446	446

×

Aurora B 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.053	0.067	-9999	-10000	0	0
STMN1	-0.11	0.12	-9999	-0.37	80	80
Aurora B/RasGAP/Survivin	-0.18	0.13	-9999	-10000	0	0
Chromosomal passenger complex/Cul3 protein complex	-0.16	0.15	-9999	-0.33	435	435
BIRC5	-0.21	0.14	-9999	-0.3	780	780
DES	-0.29	0.34	-9999	-0.65	499	499
Aurora C/Aurora B/INCENP	-0.069	0.076	-9999	-0.62	1	1
Aurora B/TACC1	-0.1	0.13	-9999	-0.61	42	42
Aurora B/PP2A	-0.098	0.097	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.008	0.017	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.003	0.003	-9999	-10000	0	0
NDC80	-0.21	0.18	-9999	-0.37	550	550
Cul3 protein complex	-0.21	0.25	-9999	-0.52	435	435
KIF2C	-0.045	0.034	-9999	-10000	0	0
PEBP1	0.002	0.005	-9999	-10000	0	0
KIF20A	-0.22	0.13	-9999	-0.3	820	820
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.098	0.097	-9999	-10000	0	0
SEPT1	-0.009	0.052	-9999	-0.29	35	35
SMC2	0	0	-9999	-10000	0	0
SMC4	-0.004	0.034	-9999	-0.29	15	15
NSUN2/NPM1/Nucleolin	0.005	0.019	-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	-0.034	0.046	-9999	-10000	0	0
AURKB	-0.16	0.15	-9999	-0.29	625	625
AURKC	-0.005	0.043	-9999	-0.32	18	18
CDCA8	-0.099	0.14	-9999	-0.3	371	371
cytokinesis	-0.11	0.08	-9999	-10000	0	0
Aurora B/Septin1	-0.098	0.088	-9999	-10000	0	0
AURKA	-0.14	0.15	-9999	-0.3	506	506
INCENP	0.003	0.005	-9999	-10000	0	0
KLHL13	-0.31	0.38	-9999	-0.79	434	434
BUB1	-0.2	0.14	-9999	-0.3	731	731
hSgo1/Aurora B/Survivin	-0.26	0.18	-9999	-0.41	538	538
EVI5	0.009	0.004	-9999	-10000	0	0
RhoA/GTP	-0.1	0.1	-9999	-0.35	14	14
SGOL1	-0.18	0.14	-9999	-0.29	682	682
CENPA	-0.059	0.064	-9999	-10000	0	0
NCAPG	-0.14	0.15	-9999	-10000	0	0
Aurora B/HC8 Proteasome	-0.098	0.097	-9999	-10000	0	0
NCAPD2	-0.002	0.025	-9999	-0.29	8	8
Aurora B/PP1-gamma	-0.098	0.097	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
NCAPH	-0.11	0.14	-9999	-0.29	422	422
NPM1	-0.019	0.025	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
KLHL9	-0.001	0.034	-9999	-0.79	2	2
mitotic prometaphase	-0.006	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.098	0.096	-9999	-10000	0	0
PPP1CC	0	0	-9999	-10000	0	0
Centraspindlin	-0.12	0.11	-9999	-0.37	37	37
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.019	0.025	-9999	-10000	0	0
MYLK	-0.088	0.15	-9999	-0.47	140	140
KIF23	-0.088	0.14	-9999	-0.3	334	334
VIM	-0.094	0.1	-9999	-0.68	2	2
RACGAP1	-0.007	0.058	-9999	-0.3	41	41
mitosis	0	0	-9999	-10000	0	0
NCL	-0.019	0.025	-9999	-10000	0	0
Chromosomal passenger complex	-0.084	0.079	-9999	-10000	0	0
Chromosomal passenger complex/EVI5	-0.16	0.18	-9999	-0.37	212	212
TACC1	-0.03	0.15	-9999	-0.79	42	42
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

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.013	0.01	-9999	-10000	0	0
RAS family/GTP	-0.11	0.14	-9999	-0.35	70	70
NFATC4	-0.087	0.16	-9999	-0.38	31	31
ERBB2IP	0.008	0.008	-9999	-10000	0	0
HSP90 (dimer)	0	0.009	-9999	-0.29	1	1
mammary gland morphogenesis	-0.15	0.18	-9999	-0.39	403	403
JUN	-0.018	0.08	-9999	-0.37	6	6
HRAS	-0.003	0.028	-9999	-0.29	10	10
DOCK7	-0.12	0.19	-9999	-0.36	403	403
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.18	0.22	-9999	-0.46	403	403
AKT1	0.008	0.005	-9999	-10000	0	0
BAD	0.018	0.006	-9999	-10000	0	0
MAPK10	-0.11	0.13	-9999	-0.35	174	174
mol:GTP	-0.001	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.16	0.2	-9999	-0.42	403	403
RAF1	-0.08	0.16	-9999	-0.41	23	23
ErbB2/ErbB3/neuregulin 2	-0.25	0.25	-9999	-0.5	528	528
STAT3	0.001	0.003	-9999	-10000	0	0
cell migration	-0.062	0.13	-9999	-0.31	94	94
mol:PI-3-4-5-P3	-0.002	0.003	-9999	-10000	0	0
cell proliferation	-0.14	0.22	-9999	-0.51	176	176
FOS	-0.16	0.26	-9999	-0.53	333	333
NRAS	-0.001	0.013	-9999	-0.3	2	2
mol:Ca2+	-0.15	0.18	-9999	-0.39	403	403
MAPK3	-0.11	0.19	-9999	-0.42	174	174
MAPK1	-0.11	0.19	-9999	-0.42	174	174
JAK2	-0.12	0.19	-9999	-0.36	404	404
NF2	-0.006	0.009	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.13	0.18	-9999	-0.36	403	403
NRG1	-0.29	0.38	-9999	-0.78	406	406
GRB2/SOS1	0	0.006	-9999	-10000	0	0
MAPK8	-0.11	0.17	-9999	-0.32	408	408
MAPK9	-0.069	0.087	-9999	-0.23	26	26
ERBB2	-0.017	0.059	-9999	-0.63	1	1
ERBB3	0	0.054	-9999	-0.79	5	5
SHC1	0.002	0.004	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
apoptosis	0.014	0.017	-9999	-10000	0	0
STAT3 (dimer)	0.001	0.003	-9999	-10000	0	0
RNF41	0.018	0.014	-9999	-10000	0	0
FRAP1	0.008	0.004	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.098	0.12	-9999	-0.33	26	26
ErbB2/ErbB2/HSP90 (dimer)	-0.013	0.046	-9999	-0.54	1	1
CHRNA1	-0.092	0.16	-9999	-0.41	58	58
myelination	-0.081	0.16	-9999	-0.36	31	31
PPP3CB	-0.12	0.18	-9999	-0.34	403	403
KRAS	-0.001	0.012	-9999	-0.29	2	2
RAC1-CDC42/GDP	-0.11	0.15	-9999	-0.39	30	30
NRG2	-0.38	0.39	-9999	-0.79	523	523
mol:GDP	-0.12	0.18	-9999	-0.35	403	403
SOS1	0	0	-9999	-10000	0	0
MAP2K2	-0.072	0.15	-9999	-0.43	17	17
SRC	0	0.009	-9999	-0.29	1	1
mol:cAMP	-0.002	0.002	-9999	-10000	0	0
PTPN11	-0.14	0.18	-9999	-0.36	403	403
MAP2K1	-0.13	0.21	-9999	-0.48	173	173
heart morphogenesis	-0.15	0.18	-9999	-0.39	403	403
RAS family/GDP	-0.11	0.14	-9999	-0.4	29	29
GRB2	0	0.009	-9999	-0.29	1	1
PRKACA	-0.01	0.014	-9999	-10000	0	0
CHRNE	0.007	0.023	-9999	-0.18	6	6
HSP90AA1	0	0.009	-9999	-0.29	1	1
activation of caspase activity	-0.008	0.005	-9999	-10000	0	0
nervous system development	-0.15	0.18	-9999	-0.39	403	403
CDC42	0	0	-9999	-10000	0	0

×

Ephrin B reverse signaling

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
EFNB2	-0.001	0.024	-10000	0	-0.79	1	1
EPHB2	-0.003	0.039	-10000	0	-0.29	19	19
EFNB1	0.017	0.05	-10000	0	-0.6	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.16	0.2	-10000	0	-0.41	424	424
Ephrin B2/EPHB1-2	-0.18	0.23	-10000	0	-0.47	424	424
neuron projection morphogenesis	-0.15	0.19	-10000	0	-0.39	424	424
Ephrin B1/EPHB1-2/Tiam1	-0.17	0.22	-10000	0	-0.44	424	424
DNM1	-0.005	0.064	-10000	0	-0.73	8	8
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.003	0.13	-10000	0	-0.74	33	33
YES1	-0.025	0.17	-10000	0	-0.98	32	32
Ephrin B1/EPHB1-2/NCK2	-0.17	0.22	-10000	0	-0.44	424	424
PI3K	-0.028	0.14	-10000	0	-0.68	45	45
mol:GDP	-0.17	0.21	-10000	0	-0.44	424	424
ITGA2B	-0.018	0.077	-10000	0	-0.32	62	62
endothelial cell proliferation	-0.001	0.016	-10000	0	-0.52	1	1
FYN	-0.025	0.16	-10000	0	-0.97	32	32
MAP3K7	-0.022	0.14	-10000	0	-0.79	32	32
FGR	-0.027	0.16	-10000	0	-0.98	32	32
TIAM1	-0.001	0.018	-10000	0	-0.29	4	4
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
RGS3	0	0	-10000	0	-10000	0	0
cell adhesion	-0.046	0.16	-10000	0	-0.62	72	72
LYN	-0.025	0.16	-10000	0	-0.97	32	32
Ephrin B1/EPHB1-2/Src Family Kinases	-0.026	0.16	-10000	0	-0.92	32	32
Ephrin B1/EPHB1-2	-0.028	0.14	-10000	0	-0.86	32	32
SRC	-0.027	0.16	-10000	0	-0.98	32	32
ITGB3	-0.028	0.14	-10000	0	-0.79	37	37
EPHB1	-0.3	0.38	-10000	0	-0.78	424	424
EPHB4	0	0.009	-10000	0	-0.29	1	1
RAC1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.001	0.017	-10000	0	-0.52	1	1
alphaIIb/beta3 Integrin	-0.033	0.12	-10000	0	-0.62	40	40
BLK	-0.027	0.17	-10000	0	-0.98	32	32
HCK	-0.027	0.16	-10000	0	-0.98	32	32
regulation of stress fiber formation	0.17	0.21	0.44	424	-10000	0	424
MAPK8	0.001	0.14	-10000	0	-0.7	38	38
Ephrin B1/EPHB1-2/RGS3	-0.17	0.22	-10000	0	-0.44	424	424
endothelial cell migration	-0.016	0.12	-10000	0	-0.68	33	33
NCK2	0	0	-10000	0	-10000	0	0
PTPN13	-0.017	0.15	-10000	0	-0.9	32	32
regulation of focal adhesion formation	0.17	0.21	0.44	424	-10000	0	424
chemotaxis	0.17	0.21	0.44	424	-10000	0	424
PIK3CA	0	0.009	-10000	0	-0.29	1	1
Rac1/GTP	-0.16	0.2	-10000	0	-0.4	424	424
angiogenesis	-0.028	0.14	-10000	0	-0.85	32	32
LCK	-0.029	0.17	-10000	0	-0.98	32	32

×

IGF1 pathway

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	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	-0.1	0.23	-10000	0	-0.48	271	271
GRB2/SOS1/SHC	0	0.004	-10000	0	-10000	0	0
HRAS	-0.003	0.028	-10000	0	-0.29	10	10
IRS1/Crk	-0.12	0.22	-10000	0	-0.48	271	271
IGF-1R heterotetramer/IGF1/PTP1B	-0.13	0.23	-10000	0	-0.53	256	256
AKT1	-0.068	0.21	-10000	0	-0.71	54	54
BAD	-0.055	0.2	-10000	0	-0.66	52	52
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.1	0.23	-10000	0	-0.48	271	271
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.12	0.23	-10000	0	-0.48	271	271
RAF1	-0.048	0.19	-10000	0	-0.62	49	49
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.11	0.21	-10000	0	-0.45	271	271
YWHAZ	-0.001	0.015	-10000	0	-0.29	3	3
IGF-1R heterotetramer/IGF1/IRS1	-0.13	0.24	-10000	0	-0.52	271	271
PIK3CA	0	0.009	-10000	0	-0.29	1	1
RPS6KB1	-0.068	0.21	-10000	0	-0.71	54	54
GNB2L1	0	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.041	0.16	-10000	0	-0.5	52	52
PXN	0	0	-10000	0	-10000	0	0
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
HRAS/GTP	-0.1	0.19	-10000	0	-0.41	257	257
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.098	0.19	-10000	0	-0.42	256	256
IGF-1R heterotetramer	-0.033	0.13	-10000	0	-0.65	36	36
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.12	0.23	-10000	0	-0.48	271	271
Crk/p130 Cas/Paxillin	-0.1	0.2	-10000	0	-0.44	256	256
IGF1R	-0.033	0.13	-10000	0	-0.66	36	36
IGF1	-0.18	0.34	-10000	0	-0.81	247	247
IRS2/Crk	-0.13	0.25	-10000	0	-0.5	274	274
PI3K	-0.12	0.22	-10000	0	-0.48	258	258
apoptosis	0.08	0.15	0.54	53	-10000	0	53
HRAS/GDP	-0.002	0.019	-10000	0	-10000	0	0
PRKCD	-0.094	0.25	-10000	0	-0.53	256	256
RAF1/14-3-3 E	-0.033	0.16	-10000	0	-0.52	49	49
BAD/14-3-3	-0.044	0.18	-10000	0	-0.59	53	53
PRKCZ	-0.068	0.21	-10000	0	-0.7	55	55
Crk/p130 Cas/Paxillin/FAK1	-0.085	0.16	-10000	0	-0.61	49	49
PTPN1	-0.003	0.029	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.13	0.24	-10000	0	-0.56	256	256
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.11	0.2	-10000	0	-0.46	256	256
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.12	0.22	-10000	0	-0.48	271	271
GRB10	0	0	-10000	0	-10000	0	0
PTPN11	-0.1	0.23	-10000	0	-0.48	271	271
IRS1	-0.12	0.25	-10000	0	-0.52	271	271
IRS2	-0.12	0.27	-10000	0	-0.53	285	285
IGF-1R heterotetramer/IGF1	-0.16	0.28	-10000	0	-0.66	256	256
GRB2	0	0.009	-10000	0	-0.29	1	1
PDPK1	-0.11	0.21	-10000	0	-0.45	258	258
YWHAE	0	0	-10000	0	-10000	0	0
PRKD1	-0.11	0.28	-10000	0	-0.56	269	269
SHC1	0	0	-10000	0	-10000	0	0

×

Nongenotropic Androgen 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	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	-0.071	0.17	-10000	0	-0.48	159	159
regulation of S phase of mitotic cell cycle	-0.044	0.12	-10000	0	-0.34	152	152
GNAO1	-0.03	0.13	-10000	0	-0.48	67	67
HRAS	-0.003	0.028	-10000	0	-0.3	10	10
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	-0.045	0.16	-10000	0	-0.42	146	146
T-DHT/AR	-0.082	0.21	-10000	0	-0.61	147	147
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.004	-10000	0	-0.007	328	328
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.045	0.18	-10000	0	-0.79	62	62
mol:GDP	-0.084	0.21	-10000	0	-0.6	152	152
cell proliferation	-0.11	0.24	-10000	0	-0.42	332	332
PIK3CA	0	0.009	-10000	0	-0.29	1	1
FOS	-0.23	0.42	-10000	0	-0.86	329	329
mol:Ca2+	-0.017	0.028	-10000	0	-0.076	151	151
MAPK3	-0.076	0.2	-10000	0	-0.45	149	149
MAPK1	-0.047	0.12	-10000	0	-0.3	66	66
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
mol:IP3	-0.001	0.002	-10000	0	-0.005	329	329
cAMP biosynthetic process	0.013	0.025	-10000	0	-10000	0	0
GNG2	-0.011	0.092	-10000	0	-0.79	15	15
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.005	329	329
HRAS/GTP	-0.068	0.15	-10000	0	-0.45	146	146
actin cytoskeleton reorganization	-0.005	0.047	-10000	0	-0.42	14	14
SRC	0	0.009	-10000	0	-0.29	1	1
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.005	329	329
PI3K	-0.007	0.059	-10000	0	-0.52	14	14
apoptosis	0.11	0.23	0.43	331	-10000	0	331
T-DHT/AR/PELP1	-0.071	0.18	-10000	0	-0.53	146	146
HRAS/GDP	-0.08	0.2	-10000	0	-0.58	148	148
CREB1	-0.12	0.24	-10000	0	-0.46	331	331
RAC1-CDC42/GTP	-0.006	0.048	-10000	0	-0.43	14	14
AR	-0.11	0.27	-10000	0	-0.79	147	147
GNB1	0	0	-10000	0	-10000	0	0
RAF1	-0.045	0.16	-10000	0	-0.44	146	146
RAC1-CDC42/GDP	-0.075	0.19	-10000	0	-0.55	146	146
T-DHT/AR/PELP1/Src	-0.065	0.16	-10000	0	-0.48	146	146
MAP2K2	-0.045	0.16	-10000	0	-0.42	146	146
T-DHT/AR/PELP1/Src/PI3K	-0.044	0.12	-10000	0	-0.35	152	152
GNAZ	-0.007	0.075	-10000	0	-0.79	10	10
SHBG	0	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.04	0.11	-10000	0	-0.48	40	40
mol:T-DHT	-0.001	0.001	0.001	63	-0.003	263	326
RAC1	0	0	-10000	0	-10000	0	0
GNRH1	0.006	0.056	-10000	0	-0.61	9	9
Gi family/GTP	-0.051	0.1	-10000	0	-0.3	98	98
CDC42	0	0	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.035	0.049	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.082	0.16	-9999	-0.46	98	98
JUN	-0.051	0.14	-9999	-0.53	27	27
HRAS	-0.003	0.028	-9999	-0.29	10	10
RET51/GFRalpha1/GDNF/GRB10	-0.15	0.2	-9999	-0.52	210	210
RAP1A	0	0	-9999	-10000	0	0
FRS2	-0.003	0.029	-9999	-0.29	11	11
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.15	0.2	-9999	-0.52	210	210
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	-0.48	206	206
RHOA	0	0	-9999	-10000	0	0
RAP1A/GTP	-0.13	0.18	-9999	-0.46	210	210
GRB7	-0.023	0.085	-9999	-0.31	79	79
RET51/GFRalpha1/GDNF	-0.15	0.2	-9999	-0.52	210	210
MAPKKK cascade	-0.1	0.16	-9999	-0.42	207	207
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.12	0.23	-9999	-0.56	213	213
lamellipodium assembly	-0.083	0.15	-9999	-0.36	210	210
RET51/GFRalpha1/GDNF/SHC	-0.15	0.2	-9999	-0.52	210	210
PIK3CA	0	0.009	-9999	-0.29	1	1
RET9/GFRalpha1/GDNF/SHC	-0.1	0.19	-9999	-0.48	206	206
RET9/GFRalpha1/GDNF/Shank3	-0.1	0.19	-9999	-0.48	206	206
MAPK3	-0.12	0.17	-9999	-0.44	207	207
DOK1	-0.001	0.018	-9999	-0.29	4	4
DOK6	-0.013	0.094	-9999	-0.63	22	22
PXN	0	0	-9999	-10000	0	0
neurite development	-0.11	0.16	-9999	-0.53	57	57
DOK5	-0.019	0.12	-9999	-0.7	30	30
GFRA1	-0.16	0.3	-9999	-0.68	257	257
MAPK8	-0.068	0.14	-9999	-0.43	57	57
HRAS/GTP	-0.12	0.18	-9999	-0.48	207	207
tube development	-0.094	0.17	-9999	-0.45	201	201
MAPK1	-0.12	0.17	-9999	-0.44	207	207
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.065	0.13	-9999	-0.33	201	201
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
PDLIM7	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.14	0.2	-9999	-0.5	216	216
SHC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.15	0.2	-9999	-0.52	210	210
RET51/GFRalpha1/GDNF/Dok5	-0.16	0.22	-9999	-0.54	226	226
PRKCA	-0.021	0.13	-9999	-0.76	31	31
HRAS/GDP	-0.002	0.019	-9999	-10000	0	0
CREB1	-0.073	0.15	-9999	-0.38	201	201
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.065	0.13	-9999	-0.33	201	201
RET51/GFRalpha1/GDNF/Grb7	-0.16	0.21	-9999	-0.54	212	212
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.11	0.16	-9999	-0.31	401	401
DOK4	0	0	-9999	-10000	0	0
JNK cascade	-0.049	0.14	-9999	-0.43	48	48
RET9/GFRalpha1/GDNF/FRS2	-0.1	0.19	-9999	-0.48	206	206
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	-0.065	0.13	-9999	-0.33	201	201
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.083	0.14	-9999	-0.35	207	207
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.082	0.14	-9999	-0.35	207	207
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.084	0.14	-9999	-0.36	207	207
PI3K	-0.13	0.24	-9999	-0.58	213	213
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.094	0.17	-9999	-0.45	201	201
GRB10	0	0	-9999	-10000	0	0
activation of MAPKK activity	-0.078	0.13	-9999	-0.33	201	201
RET51/GFRalpha1/GDNF/FRS2	-0.15	0.2	-9999	-0.52	210	210
GAB1	0	0	-9999	-10000	0	0
IRS1	-0.032	0.16	-9999	-0.79	45	45
IRS2	-0.033	0.16	-9999	-0.79	46	46
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.084	0.14	-9999	-0.36	207	207
RET51/GFRalpha1/GDNF/PKC alpha	-0.16	0.21	-9999	-0.53	237	237
GRB2	0	0.009	-9999	-0.29	1	1
PRKACA	0	0	-9999	-10000	0	0
GDNF	-0.015	0.065	-9999	-0.29	56	56
RAC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.17	0.24	-9999	-0.59	221	221
Rac1/GTP	-0.1	0.18	-9999	-0.44	210	210
RET9/GFRalpha1/GDNF	-0.11	0.21	-9999	-0.53	206	206
GFRalpha1/GDNF	-0.13	0.24	-9999	-0.6	206	206

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	-0.027	0.062	-10000	0	-0.48	2	2
epithelial cell differentiation	-0.021	0.065	-10000	0	-0.49	9	9
ITCH	0.01	0.021	-10000	0	-10000	0	0
WWP1	0.007	0.068	-10000	0	-10000	0	0
FYN	-0.001	0.034	-10000	0	-0.79	2	2
EGFR	-0.29	0.38	-10000	0	-0.78	410	410
PRL	-0.003	0.032	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.1	0.21	-10000	0	-0.46	76	76
PTPRZ1	-0.41	0.39	-10000	0	-0.78	570	570
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.16	0.2	-10000	0	-0.41	401	401
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.19	0.23	-10000	0	-0.49	401	401
ADAM17	0.01	0.021	-10000	0	-10000	0	0
ErbB4/ErbB4	0	0.086	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.055	0.13	-10000	0	-0.5	64	64
NCOR1	-0.001	0.024	-10000	0	-0.79	1	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.18	0.22	-10000	0	-0.46	401	401
GRIN2B	-0.17	0.25	-10000	0	-0.45	451	451
ErbB4/ErbB2/betacellulin	-0.05	0.11	-10000	0	-0.47	62	62
STAT1	-0.005	0.038	-10000	0	-0.29	19	19
HBEGF	-0.001	0.034	-10000	0	-0.79	2	2
PRLR	-0.008	0.071	-10000	0	-0.54	16	16
E4ICDs/ETO2	-0.035	0.09	-10000	0	-0.55	19	19
axon guidance	0.042	0.12	-10000	0	-0.43	3	3
NEDD4	0.01	0.021	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.008	0.058	-10000	0	-0.6	8	8
CBFA2T3	-0.015	0.1	-10000	0	-0.79	19	19
ErbB4/ErbB2/HBEGF	-0.026	0.054	-10000	0	-0.48	3	3
MAPK3	-0.15	0.18	-10000	0	-0.47	79	79
STAT1 (dimer)	-0.028	0.063	-10000	0	-0.31	7	7
MAPK1	-0.15	0.18	-10000	0	-0.47	79	79
JAK2	-0.001	0.024	-10000	0	-0.79	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.19	0.22	-10000	0	-0.47	401	401
NRG1	-0.21	0.3	-10000	0	-0.61	401	401
NRG3	-0.048	0.18	-10000	0	-0.62	85	85
NRG2	-0.38	0.39	-10000	0	-0.79	523	523
NRG4	-0.005	0.038	-10000	0	-0.29	19	19
heart development	0.042	0.12	-10000	0	-0.43	3	3
neural crest cell migration	-0.18	0.22	-10000	0	-0.46	401	401
ERBB2	0.009	0.062	-10000	0	-0.59	1	1
WWOX/E4ICDs	-0.026	0.059	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.19	0.21	-10000	0	-0.45	405	405
apoptosis	0.056	0.14	0.55	56	-10000	0	56
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.26	0.24	-10000	0	-0.5	523	523
ErbB4/ErbB2/epiregulin	-0.082	0.14	-10000	0	-0.45	126	126
ErbB4/ErbB4/betacellulin/betacellulin	-0.053	0.12	-10000	0	-0.5	61	61
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.023	0.067	-10000	0	-0.52	11	11
MDM2	0.008	0.075	-10000	0	-0.31	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.18	0.22	-10000	0	-0.47	401	401
STAT5A	0.043	0.12	-10000	0	-0.44	9	9
ErbB4/EGFR/neuregulin 1 beta	-0.34	0.35	-10000	0	-0.65	558	558
DLG4	0	0	-10000	0	-10000	0	0
GRB2/SHC	0	0.006	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.024	0.055	-10000	0	-0.45	1	1
STAT5A (dimer)	-0.022	0.07	-10000	0	-0.53	9	9
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.024	0.11	-10000	0	-0.42	6	6
LRIG1	-0.002	0.041	-10000	0	-0.79	3	3
EREG	-0.11	0.25	-10000	0	-0.6	203	203
BTC	-0.045	0.18	-10000	0	-0.76	64	64
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.042	0.12	-10000	0	-0.43	3	3
ERBB4	-0.032	0.072	-10000	0	-10000	0	0
STAT5B	-0.002	0.041	-10000	0	-0.79	3	3
YAP1	-0.01	0.043	-10000	0	-0.64	4	4
GRB2	0	0.009	-10000	0	-0.29	1	1
ErbB4/ErbB2/neuregulin 4	-0.027	0.055	-10000	0	-0.56	1	1
glial cell differentiation	0.024	0.055	0.45	1	-10000	0	1
WWOX	-0.001	0.013	-10000	0	-0.29	2	2
cell proliferation	-0.12	0.23	-10000	0	-0.5	136	136

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.01	0.038	-9999	-0.53	3	3
NFATC2	-0.041	0.16	-9999	-0.55	104	104
NFATC3	0.012	0.025	-9999	-10000	0	0
CD40LG	-0.22	0.36	-9999	-0.71	311	311
PTGS2	-0.32	0.46	-9999	-0.85	428	428
JUNB	-0.001	0.013	-9999	-0.29	2	2
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	0.003	-9999	-10000	0	0
JUN	-0.005	0.064	-9999	-0.8	7	7
mol:Ca2+	-0.007	0.009	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.005	-9999	-0.17	1	1
FOSL1	-0.009	0.061	-9999	-0.34	30	30
CREM	0	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.077	0.15	-9999	-0.51	87	87
FOS	-0.24	0.37	-9999	-0.8	329	329
IFNG	-0.22	0.35	-9999	-0.67	327	327
AP-1/NFAT1-c-4	-0.31	0.38	-9999	-0.81	326	326
FASLG	-0.21	0.35	-9999	-0.68	314	314
NFAT1-c-4/ICER1	-0.06	0.14	-9999	-0.46	107	107
IL2RA	-0.21	0.35	-9999	-0.68	308	308
FKBP12/FK506	0	0.006	-9999	-0.2	1	1
CSF2	-0.2	0.34	-9999	-0.67	304	304
JunB/Fra1/NFAT1-c-4	-0.057	0.14	-9999	-0.45	106	106
IL4	-0.2	0.34	-9999	-0.67	302	302
IL2	-0.009	0.024	-9999	-10000	0	0
IL3	-0.024	0.026	-9999	-10000	0	0
FKBP1A	0	0.009	-9999	-0.29	1	1
BATF3	-0.002	0.03	-9999	-0.39	5	5
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.001	0.01	-9999	-0.29	1	1

×

BMP receptor 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
BMP7/BMPR2/BMPR1A-1B/FS	-0.12	0.21	-9999	-0.6	141	141
SMAD6-7/SMURF1	0	0.016	-9999	-0.52	1	1
NOG	-0.025	0.13	-9999	-0.58	47	47
SMAD9	-0.11	0.26	-9999	-0.76	124	124
SMAD4	-0.001	0.024	-9999	-0.79	1	1
SMAD5	-0.075	0.18	-9999	-0.47	141	141
BMP7/USAG1	-0.34	0.34	-9999	-0.66	559	559
SMAD5/SKI	-0.087	0.16	-9999	-0.51	93	93
SMAD1	0.026	0.03	-9999	-10000	0	0
BMP2	-0.14	0.3	-9999	-0.78	194	194
SMAD1/SMAD1/SMAD4	-0.002	0.014	-9999	-10000	0	0
BMPR1A	-0.002	0.041	-9999	-0.79	3	3
BMPR1B	-0.14	0.18	-9999	-0.32	468	468
BMPR1A-1B/BAMBI	-0.091	0.14	-9999	-0.55	68	68
AHSG	-0.005	0.038	-9999	-0.29	19	19
CER1	-0.001	0.015	-9999	-10000	0	0
BMP2-4/CER1	-0.13	0.24	-9999	-0.56	242	242
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.1	0.2	-9999	-0.51	152	152
BMP2-4 (homodimer)	-0.14	0.27	-9999	-0.64	242	242
RGMB	-0.001	0.024	-9999	-0.79	1	1
BMP6/BMPR2/BMPR1A-1B	-0.097	0.16	-9999	-0.54	109	109
RGMA	-0.11	0.27	-9999	-0.79	147	147
SMURF1	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.11	0.2	-9999	-0.44	207	207
BMP2-4/USAG1	-0.37	0.36	-9999	-0.64	621	621
SMAD6/SMURF1/SMAD5	-0.087	0.16	-9999	-0.51	94	94
SOSTDC1	-0.38	0.39	-9999	-0.78	531	531
BMP7/BMPR2/BMPR1A-1B	-0.1	0.17	-9999	-0.57	111	111
SKI	0	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.059	0.21	-9999	-0.77	84	84
HFE2	-0.003	0.029	-9999	-10000	0	0
ZFYVE16	0	0	-9999	-10000	0	0
MAP3K7	0	0.009	-9999	-0.29	1	1
BMP2-4/CHRD	-0.14	0.26	-9999	-0.6	246	246
SMAD5/SMAD5/SMAD4	-0.087	0.16	-9999	-0.51	95	95
MAPK1	0	0	-9999	-10000	0	0
TAK1/TAB family	-0.086	0.17	-9999	-0.52	107	107
BMP7 (homodimer)	-0.075	0.22	-9999	-0.64	129	129
NUP214	0	0	-9999	-10000	0	0
BMP6/FETUA	-0.049	0.16	-9999	-0.61	82	82
SMAD1/SKI	0.004	0.018	-9999	-10000	0	0
SMAD6	-0.001	0.024	-9999	-0.79	1	1
CTDSP2	0	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.13	0.24	-9999	-0.56	242	242
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.037	0.12	-9999	-0.36	113	113
BMPR2 (homodimer)	0	0	-9999	-10000	0	0
GADD34/PP1CA	-0.001	0.009	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.091	0.12	-9999	-0.62	29	29
CHRDL1	-0.54	0.36	-9999	-0.79	750	750
ENDOFIN/SMAD1	0.004	0.018	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.003	0.013	-9999	-10000	0	0
SMAD6/SMURF1	0	0	-9999	-10000	0	0
BAMBI	-0.033	0.14	-9999	-0.5	72	72
SMURF2	0	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.47	0.36	-9999	-0.66	768	768
BMP2-4/GREM1	-0.14	0.25	-9999	-0.57	248	248
SMAD7	0	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.1	0.24	-9999	-0.72	123	123
SMAD1/SMAD6	0.004	0.018	-9999	-10000	0	0
TAK1/SMAD6	0	0.006	-9999	-10000	0	0
BMP7	-0.075	0.22	-9999	-0.64	129	129
BMP6	-0.06	0.21	-9999	-0.78	84	84
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.099	0.19	-9999	-0.59	107	107
PPM1A	0	0	-9999	-10000	0	0
SMAD1/SMURF2	0.004	0.018	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0	0	-9999	-10000	0	0
PPP1CA	-0.001	0.018	-9999	-0.29	4	4
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
PPP1R15A	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.13	0.24	-9999	-0.49	249	249
CHRD	-0.032	0.13	-9999	-0.42	83	83
BMPR2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.13	0.23	-9999	-0.54	201	201
BMP4	-0.051	0.19	-9999	-0.78	72	72
FST	-0.04	0.17	-9999	-0.76	57	57
BMP2-4/NOG	-0.14	0.26	-9999	-0.58	258	258
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.094	0.16	-9999	-0.53	111	111

×

Neurotrophic factor-mediated Trk receptor signaling

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	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	-0.1	0.12	-10000	0	-0.32	90	90
NT3 (dimer)/TRKC	-0.29	0.36	-10000	0	-0.68	465	465
NT3 (dimer)/TRKB	-0.49	0.44	-10000	0	-0.77	696	696
SHC/Grb2/SOS1/GAB1/PI3K	-0.004	0.036	-10000	0	-0.32	14	14
RAPGEF1	0	0	-10000	0	-10000	0	0
BDNF	-0.064	0.21	-10000	0	-0.66	105	105
PIK3CA	0	0.009	-10000	0	-0.29	1	1
DYNLT1	0	0	-10000	0	-10000	0	0
NTRK1	-0.011	0.07	-10000	0	-0.37	33	33
NTRK2	-0.41	0.39	-10000	0	-0.79	573	573
NTRK3	-0.27	0.37	-10000	0	-0.78	377	377
NT-4/5 (dimer)/TRKB	-0.58	0.48	-10000	0	-0.84	746	746
neuron apoptosis	0.24	0.24	0.58	300	-10000	0	300
SHC 2-3/Grb2	-0.26	0.27	-10000	0	-0.66	299	299
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.24	0.29	-10000	0	-0.67	283	283
SHC3	-0.24	0.28	-10000	0	-0.58	358	358
STAT3 (dimer)	-0.005	0.03	-10000	0	-0.38	4	4
NT3 (dimer)/TRKA	-0.24	0.31	-10000	0	-0.6	434	434
RIN/GDP	-0.065	0.12	-10000	0	-0.24	205	205
GIPC1	0	0.009	-10000	0	-0.29	1	1
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
DNAJA3	-0.14	0.2	-10000	0	-0.43	342	342
RIN/GTP	-0.001	0.01	-10000	0	-10000	0	0
CCND1	0.018	0.075	-10000	0	-1	4	4
MAGED1	-0.001	0.018	-10000	0	-0.29	4	4
PTPN11	0	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.27	0.37	-10000	0	-0.79	371	371
SHC/GRB2/SOS1	0	0.004	-10000	0	-10000	0	0
GRB2	0	0.009	-10000	0	-0.29	1	1
NGF (dimer)/TRKA/MATK	-0.028	0.11	-10000	0	-0.53	41	41
TRKA/NEDD4-2	-0.008	0.053	-10000	0	-0.6	6	6
ELMO1	0	0	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0	0	-10000	0	-10000	0	0
NGF	-0.014	0.098	-10000	0	-0.62	24	24
HRAS	-0.003	0.028	-10000	0	-0.29	10	10
DOCK1	0	0	-10000	0	-10000	0	0
GAB2	-0.004	0.042	-10000	0	-0.39	10	10
RIT2	-0.001	0.015	-10000	0	-0.29	3	3
RIT1	0	0	-10000	0	-10000	0	0
FRS2	-0.003	0.029	-10000	0	-0.29	11	11
DNM1	-0.005	0.063	-10000	0	-0.73	8	8
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	-0.13	0.2	-10000	0	-0.42	342	342
mol:GDP	-0.1	0.18	-10000	0	-0.35	275	275
NGF (dimer)	-0.014	0.097	-10000	0	-0.62	24	24
RhoG/GDP	0	0	-10000	0	-10000	0	0
RIT1/GDP	-0.061	0.12	-10000	0	-0.24	228	228
TIAM1	-0.001	0.018	-10000	0	-0.29	4	4
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
BDNF (dimer)/TRKB	-0.31	0.3	-10000	0	-0.56	598	598
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)	-0.13	0.29	-10000	0	-0.75	185	185
RAP1/GDP	-0.072	0.084	-10000	0	-0.24	42	42
KIDINS220/CRKL	0	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.064	0.21	-10000	0	-0.66	105	105
ubiquitin-dependent protein catabolic process	-0.015	0.076	-10000	0	-0.51	22	22
Schwann cell development	-0.058	0.044	-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	-0.001	0.011	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.42	0.38	-10000	0	-0.65	711	711
ABL1	0	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
Rap1/GTP	-0.1	0.097	-10000	0	-10000	0	0
STAT3	-0.005	0.03	-10000	0	-0.38	4	4
axon guidance	-0.4	0.34	-10000	0	-0.61	711	711
MAPK3	0.006	0.1	-10000	0	-0.5	38	38
MAPK1	0.006	0.1	-10000	0	-0.5	38	38
CDC42/GDP	-0.061	0.12	-10000	0	-0.24	230	230
NTF3	-0.13	0.29	-10000	0	-0.75	185	185
NTF4	-0.27	0.37	-10000	0	-0.79	371	371
NGF (dimer)/TRKA/FAIM	-0.015	0.075	-10000	0	-0.52	21	21
PI3K	-0.008	0.068	-10000	0	-0.6	14	14
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	-0.15	0.21	-10000	0	-0.45	345	345
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.24	0.33	-10000	0	-0.59	467	467
RGS19	-0.001	0.013	-10000	0	-0.29	2	2
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.082	-10000	0	-10000	0	0
Rac1/GDP	-0.061	0.12	-10000	0	-0.25	120	120
NGF (dimer)/TRKA/GRIT	-0.015	0.076	-10000	0	-0.52	21	21
neuron projection morphogenesis	-0.1	0.21	-10000	0	-0.62	29	29
NGF (dimer)/TRKA/NEDD4-2	-0.015	0.076	-10000	0	-0.52	22	22
MAP2K1	0	0.003	-10000	0	-10000	0	0
NGFR	-0.24	0.36	-10000	0	-0.79	334	334
NGF (dimer)/TRKA/GIPC/GAIP	-0.009	0.053	-10000	0	-0.33	27	27
RAS family/GTP/PI3K	-0.005	0.038	-10000	0	-0.34	14	14
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.011	-10000	0	-10000	0	0
NRAS	-0.001	0.013	-10000	0	-0.29	2	2
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
PRKCI	0	0.009	-10000	0	-0.29	1	1
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	-0.001	0.024	-10000	0	-0.79	1	1
MAPKKK cascade	-0.064	0.12	-10000	0	-0.82	21	21
RASA1	0	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.008	0.05	-10000	0	-0.6	5	5
SQSTM1	0	0.009	-10000	0	-0.29	1	1
BDNF (dimer)/TRKB/GIPC	-0.28	0.27	-10000	0	-0.51	598	598
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.012	0.064	-10000	0	-0.44	22	22
MATK	-0.022	0.11	-10000	0	-0.48	49	49
NEDD4L	-0.001	0.024	-10000	0	-0.79	1	1
RAS family/GDP	-0.065	0.078	-10000	0	-0.23	15	15
NGF (dimer)/TRKA	-0.15	0.22	-10000	0	-0.46	342	342
Rac1/GTP	-0.12	0.14	-10000	0	-0.34	261	261
FRS2 family/SHP2/CRK family	-0.001	0.01	-10000	0	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.095	0.18	-10000	0	-0.46	197	197
ER alpha/Gai/GDP/Gbeta gamma	-0.093	0.19	-10000	0	-0.47	189	189
AKT1	-0.1	0.32	-10000	0	-0.83	171	171
PIK3CA	0	0.009	-10000	0	-0.29	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.1	0.32	-10000	0	-0.85	168	168
mol:Ca2+	-0.028	0.15	-10000	0	-0.45	93	93
IGF1R	-0.02	0.12	-10000	0	-0.6	36	36
E2/ER alpha (dimer)/Striatin	-0.11	0.2	-10000	0	-0.53	183	183
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	0.094	0.3	0.78	171	-10000	0	171
RhoA/GTP	-0.069	0.14	-10000	0	-0.39	165	165
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.093	0.2	-10000	0	-0.54	175	175
regulation of stress fiber formation	0.023	0.14	0.36	35	-10000	0	35
E2/ERA-ERB (dimer)	-0.11	0.2	-10000	0	-0.54	187	187
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
G13/GTP	-0.088	0.17	-10000	0	-0.48	165	165
pseudopodium formation	-0.023	0.14	-10000	0	-0.36	35	35
E2/ER alpha (dimer)/PELP1	-0.096	0.19	-10000	0	-0.52	165	165
GRB2	0	0.009	-10000	0	-0.29	1	1
GNG2	-0.011	0.092	-10000	0	-0.79	15	15
GNAO1	-0.03	0.13	-10000	0	-0.48	67	67
HRAS	-0.003	0.028	-10000	0	-0.29	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.061	0.22	-10000	0	-0.54	179	179
E2/ER beta (dimer)	-0.013	0.089	-10000	0	-0.61	24	24
mol:GDP	-0.086	0.2	-10000	0	-0.53	187	187
mol:NADP	-0.061	0.22	-10000	0	-0.54	179	179
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
mol:IP3	-0.03	0.15	-10000	0	-0.47	93	93
IGF-1R heterotetramer	-0.02	0.12	-10000	0	-0.59	36	36
PLCB1	-0.065	0.14	-10000	0	-0.49	92	92
PLCB2	-0.034	0.089	-10000	0	-0.62	15	15
IGF1	-0.18	0.33	-10000	0	-0.79	247	247
mol:L-citrulline	-0.061	0.22	-10000	0	-0.54	179	179
RHOA	0	0	-10000	0	-10000	0	0
Gai/GDP	-0.04	0.15	-10000	0	-0.85	26	26
JNK cascade	-0.013	0.089	-10000	0	-0.61	24	24
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	-0.017	0.12	-10000	0	-0.79	24	24
GNAQ	-0.002	0.041	-10000	0	-0.79	3	3
ESR1	-0.15	0.28	-10000	0	-0.58	288	288
Gq family/GDP/Gbeta gamma	-0.009	0.078	-10000	0	-0.71	9	9
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.023	0.13	-10000	0	-0.32	165	165
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.093	0.2	-10000	0	-0.54	175	175
GNAZ	-0.007	0.075	-10000	0	-0.79	10	10
E2/ER alpha (dimer)	-0.11	0.22	-10000	0	-0.61	165	165
STRN	-0.015	0.11	-10000	0	-0.79	21	21
GNAL	-0.19	0.33	-10000	0	-0.79	258	258
PELP1	0	0	-10000	0	-10000	0	0
MAPK11	0.005	0.084	-10000	0	-0.52	27	27
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.045	0.18	-10000	0	-0.79	62	62
HBEGF	-0.071	0.19	-10000	0	-0.45	187	187
cAMP biosynthetic process	-0.19	0.25	-10000	0	-0.5	389	389
SRC	-0.052	0.2	-10000	0	-0.45	177	177
PI3K	-0.008	0.068	-10000	0	-0.6	14	14
GNB1	0	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.079	0.18	-10000	0	-0.46	197	197
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.15	0.23	-10000	0	-0.51	246	246
Gs family/GTP	-0.19	0.26	-10000	0	-0.52	389	389
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.002	0.014	-10000	0	-10000	0	0
vasodilation	-0.057	0.21	-10000	0	-0.51	179	179
mol:DAG	-0.03	0.15	-10000	0	-0.47	93	93
Gs family/GDP/Gbeta gamma	-0.16	0.23	-10000	0	-0.44	391	391
MSN	-0.027	0.15	-10000	0	-0.39	35	35
Gq family/GTP	-0.038	0.094	-10000	0	-0.66	14	14
mol:PI-3-4-5-P3	-0.099	0.31	-10000	0	-0.81	168	168
NRAS	-0.001	0.013	-10000	0	-0.29	2	2
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.057	0.21	0.51	179	-10000	0	179
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
RhoA/GDP	-0.079	0.19	-10000	0	-0.49	187	187
NOS3	-0.066	0.24	-10000	0	-0.57	179	179
GNA11	-0.003	0.048	-10000	0	-0.79	4	4
MAPKKK cascade	-0.069	0.26	-10000	0	-0.63	183	183
E2/ER alpha (dimer)/PELP1/Src	-0.098	0.22	-10000	0	-0.56	175	175
ruffle organization	-0.023	0.14	-10000	0	-0.36	35	35
ROCK2	-0.074	0.14	-10000	0	-0.37	194	194
GNA14	-0.013	0.084	-10000	0	-0.46	30	30
GNA15	-0.003	0.033	-10000	0	-0.36	8	8
GNA13	0	0	-10000	0	-10000	0	0
MMP9	-0.097	0.2	-10000	0	-0.48	184	184
MMP2	-0.045	0.19	-10000	0	-0.43	184	184

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.075	0.23	-9999	-0.79	104	104
GNB1/GNG2	-0.14	0.23	-9999	-0.68	116	116
mol:DAG	-0.097	0.22	-9999	-0.6	116	116
PLCG1	-0.13	0.21	-9999	-0.63	116	116
YES1	-0.14	0.23	-9999	-0.66	120	120
FZD3	-0.011	0.092	-9999	-0.79	15	15
FZD6	-0.007	0.075	-9999	-0.79	10	10
G protein	-0.13	0.22	-9999	-0.64	118	118
MAP3K7	-0.069	0.19	-9999	-0.49	113	113
mol:Ca2+	-0.093	0.22	-9999	-0.58	116	116
mol:IP3	-0.097	0.22	-9999	-0.6	116	116
NLK	-0.005	0.01	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
CAMK2A	-0.083	0.2	-9999	-0.54	114	114
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.16	0.25	-9999	-0.44	385	385
CSNK1A1	0	0	-9999	-10000	0	0
GNAS	-0.14	0.23	-9999	-0.66	121	121
GO:0007205	-0.094	0.22	-9999	-0.59	116	116
WNT6	-0.16	0.31	-9999	-0.69	255	255
WNT4	-0.021	0.12	-9999	-0.55	43	43
NFAT1/CK1 alpha	-0.16	0.23	-9999	-0.63	145	145
GNG2	-0.011	0.092	-9999	-0.79	15	15
WNT5A	-0.016	0.1	-9999	-0.79	18	18
WNT11	-0.17	0.32	-9999	-0.76	242	242
CDC42	-0.11	0.24	-9999	-0.66	105	105

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.22	0.26	-10000	0	-0.52	452	452
fibroblast growth factor receptor signaling pathway	-0.22	0.26	-10000	0	-0.52	452	452
LAMA1	-0.088	0.25	-10000	0	-0.77	124	124
PRNP	-0.013	0.1	-10000	0	-0.79	18	18
GPC1/SLIT2	-0.07	0.19	-10000	0	-0.6	125	125
SMAD2	0.01	0.1	-10000	0	-0.47	50	50
GPC1/PrPc/Cu2+	-0.01	0.069	-10000	0	-0.52	19	19
GPC1/Laminin alpha1	-0.068	0.19	-10000	0	-0.6	121	121
TDGF1	-0.005	0.063	-10000	0	-0.73	8	8
CRIPTO/GPC1	-0.006	0.053	-10000	0	-0.6	8	8
APP/GPC1	-0.002	0.023	-10000	0	-0.6	1	1
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.02	0.051	-10000	0	-0.52	9	9
FLT1	-0.001	0.024	-10000	0	-0.79	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.025	0.11	-10000	0	-0.52	50	50
SERPINC1	-0.018	0.07	-10000	0	-0.29	67	67
FYN	0.02	0.053	-10000	0	-0.52	10	10
FGR	0.02	0.051	-10000	0	-0.52	9	9
positive regulation of MAPKKK cascade	0.032	0.066	-10000	0	-0.52	10	10
SLIT2	-0.089	0.25	-10000	0	-0.79	124	124
GPC1/NRG	-0.22	0.29	-10000	0	-0.6	402	402
NRG1	-0.29	0.38	-10000	0	-0.78	406	406
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.003	0.029	-10000	0	-0.52	2	2
LYN	0.021	0.048	-10000	0	-0.51	8	8
mol:Spermine	0.009	0.024	-10000	0	-0.61	1	1
cell growth	-0.22	0.26	-10000	0	-0.52	452	452
BMP signaling pathway	0.002	0.032	0.36	7	-10000	0	7
SRC	0.021	0.048	-10000	0	-0.51	8	8
TGFBR1	0	0.009	-10000	0	-0.29	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.26	0.37	-10000	0	-0.75	382	382
GPC1	-0.002	0.032	-10000	0	-0.36	7	7
TGFBR1 (dimer)	0	0.009	-10000	0	-0.29	1	1
VEGFA	-0.003	0.031	-10000	0	-0.29	12	12
BLK	-0.006	0.082	-10000	0	-0.56	10	10
HCK	0.018	0.052	-10000	0	-0.51	8	8
FGF2	-0.32	0.39	-10000	0	-0.79	446	446
FGFR1	-0.009	0.08	-10000	0	-0.68	14	14
VEGFR1 homodimer	-0.001	0.024	-10000	0	-0.79	1	1
TGFBR2	-0.035	0.16	-10000	0	-0.79	49	49
cell death	-0.002	0.023	-10000	0	-0.6	1	1
ATIII/GPC1	-0.013	0.05	-10000	0	-0.61	1	1
PLA2G2A/GPC1	-0.2	0.28	-10000	0	-0.6	356	356
LCK	0.008	0.082	-10000	0	-0.53	21	21
neuron differentiation	-0.22	0.29	-10000	0	-0.6	402	402
PrPc/Cu2+	-0.01	0.077	-10000	0	-0.61	18	18
APP	0	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	-0.035	0.16	-10000	0	-0.79	49	49

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.16	0.39	-9999	-0.91	130	130
IL23A	-0.17	0.39	-9999	-1	93	93
NF kappa B1 p50/RelA/I kappa B alpha	-0.23	0.32	-9999	-0.88	140	140
positive regulation of T cell mediated cytotoxicity	-0.18	0.42	-9999	-0.85	231	231
ITGA3	-0.16	0.38	-9999	-0.97	98	98
IL17F	-0.1	0.28	-9999	-0.64	100	100
IL12B	-0.05	0.12	-9999	-0.31	115	115
STAT1 (dimer)	-0.21	0.37	-9999	-0.84	206	206
CD4	-0.16	0.38	-9999	-0.87	128	128
IL23	-0.17	0.38	-9999	-0.99	93	93
IL23R	-0.012	0.087	-9999	-10000	0	0
IL1B	-0.17	0.41	-9999	-0.97	130	130
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.16	0.38	-9999	-0.96	95	95
TYK2	0.012	0.017	-9999	-10000	0	0
STAT4	-0.032	0.16	-9999	-0.78	45	45
STAT3	0	0	-9999	-10000	0	0
IL18RAP	-0.021	0.14	-9999	-0.73	42	42
IL12RB1	-0.001	0.07	-9999	-0.32	43	43
PIK3CA	0	0.009	-9999	-0.29	1	1
IL12Rbeta1/TYK2	-0.002	0.052	-9999	-0.6	2	2
IL23R/JAK2	-0.009	0.11	-9999	-0.63	1	1
positive regulation of chronic inflammatory response	-0.18	0.42	-9999	-0.85	231	231
natural killer cell activation	0.002	0.008	-9999	-10000	0	0
JAK2	0.018	0.034	-9999	-0.83	1	1
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
NFKB1	0.005	0.007	-9999	-10000	0	0
RELA	0.005	0.007	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.16	0.37	-9999	-0.94	94	94
ALOX12B	-0.16	0.38	-9999	-0.95	94	94
CXCL1	-0.34	0.63	-9999	-1.4	278	278
T cell proliferation	-0.18	0.42	-9999	-0.85	231	231
NFKBIA	0.005	0.007	-9999	-10000	0	0
IL17A	-0.068	0.24	-9999	-0.54	59	59
PI3K	-0.24	0.32	-9999	-0.82	198	198
IFNG	-0.005	0.027	-9999	-0.089	23	23
STAT3 (dimer)	-0.23	0.31	-9999	-0.85	143	143
IL18R1	-0.007	0.11	-9999	-0.78	20	20
IL23/IL23R/JAK2/TYK2/SOCS3	-0.081	0.24	-9999	-0.57	48	48
IL18/IL18R	-0.03	0.12	-9999	-0.53	56	56
macrophage activation	-0.013	0.016	-9999	-0.041	135	135
TNF	-0.17	0.4	-9999	-1	103	103
STAT3/STAT4	-0.25	0.34	-9999	-0.86	200	200
STAT4 (dimer)	-0.23	0.39	-9999	-0.88	217	217
IL18	0.001	0.047	-9999	-0.3	27	27
IL19	-0.17	0.38	-9999	-0.92	115	115
STAT5A (dimer)	-0.21	0.37	-9999	-0.84	215	215
STAT1	-0.005	0.038	-9999	-0.29	19	19
SOCS3	-0.004	0.058	-9999	-0.79	6	6
CXCL9	-0.18	0.38	-9999	-0.97	103	103
MPO	-0.2	0.46	-9999	-1.1	159	159
positive regulation of humoral immune response	-0.18	0.42	-9999	-0.85	231	231
IL23/IL23R/JAK2/TYK2	-0.19	0.44	-9999	-0.88	231	231
IL6	-0.46	0.7	-9999	-1.3	408	408
STAT5A	-0.006	0.067	-9999	-0.79	8	8
IL2	0.004	0.028	-9999	-0.3	8	8
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.008	-9999	-10000	0	0
CD3E	-0.17	0.41	-9999	-0.95	141	141
keratinocyte proliferation	-0.18	0.42	-9999	-0.85	231	231
NOS2	-0.16	0.38	-9999	-0.9	131	131

×

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

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
MET/RANBP9	-0.1	0.23	-10000	0	-0.6	188	188
CRKL	-0.04	0.16	-10000	0	-0.34	188	188
mol:PIP3	-0.018	0.035	0.77	2	-10000	0	2
AKT1	0.003	0.021	0.48	2	-10000	0	2
PTK2B	0	0	-10000	0	-10000	0	0
RAPGEF1	-0.03	0.15	-10000	0	-0.54	21	21
RANBP10	0	0	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.29	1	1
HGF/MET/SHIP2	-0.12	0.24	-10000	0	-0.56	240	240
MAP3K5	-0.021	0.15	-10000	0	-0.53	25	25
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.11	0.22	-10000	0	-0.51	240	240
AP1	-0.19	0.26	-10000	0	-0.58	330	330
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	330	330
STAT3 (dimer)	-0.039	0.16	-10000	0	-0.62	21	21
GAB1/CRKL/SHP2/PI3K	-0.066	0.13	-10000	0	-0.52	35	35
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	-0.032	0.15	-10000	0	-0.54	21	21
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	-0.001	0.034	-10000	0	-0.79	2	2
ELK1	-0.044	0.1	-10000	0	-0.27	188	188
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.046	0.092	-10000	0	-0.41	21	21
PAK1	0.008	0.028	0.45	2	-10000	0	2
HGF/MET/RANBP10	-0.12	0.24	-10000	0	-0.56	240	240
HRAS	-0.15	0.3	-10000	0	-0.68	240	240
DOCK1	-0.03	0.15	-10000	0	-0.54	21	21
GAB1	-0.05	0.16	-10000	0	-0.35	240	240
CRK	-0.04	0.16	-10000	0	-0.34	188	188
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.15	0.3	-10000	0	-0.7	240	240
JUN	-0.005	0.063	-10000	0	-0.79	7	7
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.078	0.15	-10000	0	-0.35	240	240
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
cell morphogenesis	-0.019	0.18	-10000	0	-0.59	31	31
GRB2/SHC	-0.066	0.13	-10000	0	-0.33	188	188
FOS	-0.24	0.36	-10000	0	-0.79	329	329
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.044	0.1	-10000	0	-0.27	188	188
HGF/MET/MUC20	-0.12	0.24	-10000	0	-0.56	240	240
cell migration	-0.065	0.13	-10000	0	-0.32	188	188
GRB2	0	0.009	-10000	0	-0.29	1	1
CBL	0	0	-10000	0	-10000	0	0
MET/RANBP10	-0.1	0.23	-10000	0	-0.6	188	188
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.077	0.15	-10000	0	-0.35	240	240
MET/MUC20	-0.1	0.23	-10000	0	-0.61	189	189
RAP1B	-0.021	0.14	-10000	0	-0.5	21	21
RAP1A	-0.021	0.14	-10000	0	-0.5	21	21
HGF/MET/RANBP9	-0.12	0.24	-10000	0	-0.56	240	240
RAF1	-0.1	0.29	-10000	0	-0.7	191	191
STAT3	-0.073	0.14	-10000	0	-0.63	21	21
cell proliferation	-0.061	0.23	-10000	0	-0.48	240	240
RPS6KB1	-0.027	0.052	-10000	0	-0.18	21	21
MAPK3	-0.044	0.092	-10000	0	-0.24	188	188
MAPK1	-0.044	0.092	-10000	0	-0.24	188	188
RANBP9	0	0	-10000	0	-10000	0	0
MAPK8	-0.004	0.14	-10000	0	-0.48	33	33
SRC	-0.071	0.14	-10000	0	-0.61	21	21
PI3K	-0.072	0.14	-10000	0	-0.35	197	197
MET/Glomulin	-0.094	0.21	-10000	0	-0.55	188	188
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	-0.086	0.27	-10000	0	-0.64	188	188
MET	-0.14	0.3	-10000	0	-0.78	189	189
MAP4K1	-0.03	0.15	-10000	0	-0.51	26	26
PTK2	0	0	-10000	0	-10000	0	0
MAP2K2	-0.086	0.27	-10000	0	-0.64	188	188
BAD	0.011	0.02	0.45	2	-10000	0	2
MAP2K4	-0.011	0.14	-10000	0	-0.47	26	26
SHP2/GRB2/SOS1/GAB1	-0.096	0.19	-10000	0	-0.5	188	188
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	-0.35	188	188
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.053	0.2	-10000	0	-0.79	73	73
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	-0.067	0.13	-10000	0	-0.32	188	188
PDPK1	-0.006	0.025	0.56	2	-10000	0	2
HGF/MET/SHIP	-0.12	0.24	-10000	0	-0.56	240	240

×

Syndecan-1-mediated signaling events

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
TGFB1	-0.001	0.015	-9999	-0.29	3	3
CCL5	-0.014	0.079	-9999	-0.36	44	44
SDCBP	0	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.08	0.11	-9999	-0.34	106	106
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.074	0.096	-9999	-0.35	46	46
Syndecan-1/Syntenin	-0.074	0.096	-9999	-0.48	6	6
MAPK3	-0.047	0.095	-9999	-0.48	5	5
HGF/MET	-0.14	0.27	-9999	-0.64	240	240
TGFB1/TGF beta receptor Type II	-0.001	0.015	-9999	-0.29	3	3
BSG	0	0.009	-9999	-0.29	1	1
keratinocyte migration	-0.073	0.095	-9999	-0.35	46	46
Syndecan-1/RANTES	-0.081	0.11	-9999	-0.39	50	50
Syndecan-1/CD147	-0.065	0.093	-9999	-0.49	6	6
Syndecan-1/Syntenin/PIP2	-0.071	0.093	-9999	-0.46	6	6
LAMA5	0	0.009	-9999	-0.29	1	1
positive regulation of cell-cell adhesion	-0.07	0.091	-9999	-0.33	46	46
MMP7	-0.12	0.28	-9999	-0.7	191	191
HGF	-0.053	0.2	-9999	-0.79	73	73
Syndecan-1/CASK	-0.076	0.1	-9999	-0.33	106	106
Syndecan-1/HGF/MET	-0.17	0.24	-9999	-0.58	243	243
regulation of cell adhesion	-0.038	0.093	-9999	-0.48	4	4
HPSE	-0.007	0.051	-9999	-0.34	21	21
positive regulation of cell migration	-0.08	0.11	-9999	-0.34	106	106
SDC1	-0.08	0.11	-9999	-0.35	106	106
Syndecan-1/Collagen	-0.08	0.11	-9999	-0.34	106	106
PPIB	-0.001	0.015	-9999	-0.29	3	3
MET	-0.14	0.3	-9999	-0.78	189	189
PRKACA	0	0	-9999	-10000	0	0
MMP9	-0.13	0.15	-9999	-0.29	483	483
MAPK1	-0.047	0.095	-9999	-0.48	5	5
homophilic cell adhesion	-0.079	0.11	-9999	-0.34	106	106
MMP1	-0.22	0.13	-9999	-0.29	824	824

×

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	-0.076	0.068	-9999	-0.61	1	1
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.02	0.018	-9999	-10000	0	0
AURKB	-0.17	0.14	-9999	-0.29	625	625
AURKC	-0.005	0.043	-9999	-0.32	18	18

×

Visual signal transduction: Rods

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0	0	-9999	-10000	0	0
GNAT1/GTP	-0.003	0.023	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.01	0.04	-9999	-0.31	2	2
PDE6G/GNAT1/GTP	-0.008	0.036	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.004	0.034	-9999	-10000	0	0
GRK1	-0.003	0.029	-9999	-0.29	11	11
CNG Channel	-0.14	0.2	-9999	-0.43	316	316
mol:Na +	-0.13	0.18	-9999	-0.41	309	309
mol:ADP	-0.003	0.029	-9999	-0.29	11	11
RGS9-1/Gbeta5/R9AP	-0.061	0.16	-9999	-0.53	106	106
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.13	0.19	-9999	-0.42	309	309
CNGB1	-0.015	0.064	-9999	-0.29	55	55
RDH5	-0.48	0.38	-9999	-0.79	660	660
SAG	-0.015	0.064	-9999	-0.29	55	55
mol:Ca2+	-0.12	0.18	-9999	-0.4	186	186
Na + (4 Units)	-0.12	0.17	-9999	-0.39	186	186
RGS9	-0.08	0.23	-9999	-0.73	121	121
GNB1/GNGT1	-0.03	0.068	-9999	-10000	0	0
GNAT1/GDP	-0.054	0.14	-9999	-0.46	106	106
GUCY2D	-0.008	0.057	-9999	-0.36	24	24
GNGT1	-0.047	0.11	-9999	-0.29	175	175
GUCY2F	-0.001	0.013	-9999	-0.29	2	2
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.018	0.069	-9999	-0.45	22	22
mol:11-cis-retinal	-0.48	0.38	-9999	-0.79	660	660
mol:cGMP	-0.011	0.048	-9999	-0.45	8	8
GNB1	0	0	-9999	-10000	0	0
Rhodopsin	-0.37	0.29	-9999	-0.6	660	660
SLC24A1	0	0	-9999	-10000	0	0
CNGA1	-0.22	0.35	-9999	-0.78	310	310
Metarhodopsin II	-0.003	0.022	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.012	0.051	-9999	-0.48	8	8
RGS9BP	-0.019	0.072	-9999	-0.29	70	70
Metarhodopsin II/Transducin	-0.009	0.021	-9999	-10000	0	0
GCAP Family/Ca ++	-0.008	0.042	-9999	-0.48	5	5
PDE6A/B	-0.017	0.089	-9999	-0.6	22	22
mol:Pi	-0.061	0.16	-9999	-0.52	106	106
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.023	0.051	-9999	-10000	0	0
PDE6B	-0.017	0.11	-9999	-0.73	25	25
PDE6A	-0.006	0.042	-9999	-0.29	23	23
PDE6G	-0.012	0.058	-9999	-0.29	44	44
RHO	-0.004	0.035	-9999	-0.29	16	16
PDE6	-0.062	0.14	-9999	-0.44	124	124
GUCA1A	-0.012	0.059	-9999	-0.29	46	46
GC2/GCAP Family	-0.008	0.043	-9999	-0.48	5	5
GUCA1C	0	0.009	-9999	-0.29	1	1
GUCA1B	-0.004	0.053	-9999	-0.79	5	5

×

Signaling events mediated by PTP1B

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.003	0.048	-10000	0	-0.79	4	4
Jak2/Leptin Receptor	-0.16	0.23	-10000	0	-0.52	299	299
PTP1B/AKT1	-0.07	0.11	-10000	0	-0.34	115	115
FYN	-0.001	0.034	-10000	0	-0.79	2	2
p210 bcr-abl/PTP1B	-0.071	0.13	-10000	0	-0.38	119	119
EGFR	-0.29	0.39	-10000	0	-0.79	410	410
EGF/EGFR	-0.29	0.3	-10000	0	-0.56	554	554
CSF1	-0.006	0.071	-10000	0	-0.79	9	9
AKT1	0.001	0.003	-10000	0	-10000	0	0
INSR	0.001	0.01	-10000	0	-0.3	1	1
PTP1B/N-cadherin	-0.097	0.12	-10000	0	-0.37	123	123
Insulin Receptor/Insulin	-0.049	0.08	-10000	0	-0.4	22	22
HCK	-0.004	0.033	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
TYK2	-0.06	0.12	-10000	0	-0.36	117	117
EGF	-0.15	0.32	-10000	0	-0.79	214	214
YES1	-0.001	0.024	-10000	0	-0.79	1	1
CAV1	-0.18	0.24	-10000	0	-0.51	294	294
TXN	0	0.018	-10000	0	-0.3	4	4
PTP1B/IRS1/GRB2	-0.087	0.14	-10000	0	-0.4	151	151
cell migration	0.071	0.13	0.38	119	-10000	0	119
STAT3	0	0.001	-10000	0	-10000	0	0
PRLR	-0.006	0.072	-10000	0	-0.54	16	16
ITGA2B	-0.018	0.078	-10000	0	-0.32	62	62
CSF1R	-0.001	0.025	-10000	0	-0.54	2	2
Prolactin Receptor/Prolactin	-0.007	0.058	-10000	0	-0.6	8	8
FGR	-0.001	0.025	-10000	0	-0.54	2	2
PTP1B/p130 Cas	-0.074	0.12	-10000	0	-0.36	117	117
Crk/p130 Cas	-0.069	0.11	-10000	0	-0.35	105	105
DOK1	-0.046	0.12	-10000	0	-0.33	99	99
JAK2	-0.042	0.08	-10000	0	-0.32	30	30
Jak2/Leptin Receptor/Leptin	-0.36	0.18	-10000	0	-0.49	576	576
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
PTPN1	-0.072	0.13	-10000	0	-0.39	119	119
LYN	0	0	-10000	0	-10000	0	0
CDH2	-0.054	0.12	-10000	0	-0.3	200	200
SRC	-0.013	0.047	-10000	0	-10000	0	0
ITGB3	-0.028	0.14	-10000	0	-0.79	37	37
CAT1/PTP1B	-0.084	0.17	-10000	0	-0.43	116	116
CAPN1	0.001	0.01	-10000	0	-0.29	1	1
CSK	0	0	-10000	0	-10000	0	0
PI3K	-0.044	0.094	-10000	0	-0.55	20	20
mol:H2O2	-0.005	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.32	0.16	-10000	0	-0.43	551	551
negative regulation of transcription	-0.041	0.079	-10000	0	-0.32	30	30
FCGR2A	-0.001	0.013	-10000	0	-0.29	2	2
FER	-0.007	0.08	-10000	0	-0.8	11	11
alphaIIb/beta3 Integrin	-0.033	0.12	-10000	0	-0.62	40	40
BLK	-0.044	0.11	-10000	0	-0.3	159	159
Insulin Receptor/Insulin/Shc	0	0.005	-10000	0	-10000	0	0
RHOA	0.002	0.004	-10000	0	-10000	0	0
LEPR	-0.2	0.35	-10000	0	-0.79	292	292
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0	0.009	-10000	0	-0.29	1	1
mol:NADPH	-0.005	0.005	-10000	0	-10000	0	0
TRPV6	-0.03	0.13	-10000	0	-0.44	22	22
PRL	-0.004	0.032	-10000	0	-0.33	1	1
SOCS3	0.018	0.11	-10000	0	-1.5	6	6
SPRY2	-0.095	0.26	-10000	0	-0.8	130	130
Insulin Receptor/Insulin/IRS1	-0.022	0.11	-10000	0	-0.53	45	45
CSF1/CSF1R	-0.073	0.12	-10000	0	-0.37	108	108
Ras protein signal transduction	0.037	0.036	-10000	0	-0.21	1	1
IRS1	-0.032	0.16	-10000	0	-0.79	45	45
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.64	0.31	-10000	0	-0.79	881	881
STAT5B	-0.058	0.11	-10000	0	-0.31	122	122
STAT5A	-0.059	0.11	-10000	0	-0.31	125	125
GRB2	0	0.009	-10000	0	-0.29	1	1
PDGFB-D/PDGFRB	-0.076	0.12	-10000	0	-0.37	119	119
CSN2	0.018	0.035	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.29	1	1
LAT	-0.014	0.053	-10000	0	-0.57	2	2
YBX1	-0.001	0.014	-10000	0	-10000	0	0
LCK	-0.02	0.1	-10000	0	-0.41	53	53
SHC1	0	0	-10000	0	-10000	0	0
NOX4	-0.004	0.05	-10000	0	-0.41	13	13

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.065	0.22	-9999	-0.64	55	55
CRP	-0.07	0.22	-9999	-0.67	46	46
cell cycle arrest	-0.084	0.24	-9999	-0.71	71	71
TIMP1	-0.063	0.2	-9999	-0.56	63	63
IL6ST	-0.086	0.26	-9999	-0.78	137	137
Rac1/GDP	-0.12	0.23	-9999	-0.67	91	91
AP1	-0.13	0.23	-9999	-0.48	282	282
GAB2	0.005	0.043	-9999	-0.39	10	10
TNFSF11	-0.076	0.22	-9999	-0.66	49	49
HSP90B1	0.015	0.047	-9999	-10000	0	0
GAB1	0.008	0.006	-9999	-10000	0	0
MAPK14	-0.13	0.25	-9999	-0.72	97	97
AKT1	0.038	0.042	-9999	-10000	0	0
FOXO1	0.046	0.061	-9999	-0.42	12	12
MAP2K6	-0.15	0.26	-9999	-0.66	128	128
mol:GTP	0	0.001	-9999	-10000	0	0
MAP2K4	-0.086	0.23	-9999	-0.64	88	88
MITF	-0.14	0.26	-9999	-0.67	113	113
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0	0	-9999	-10000	0	0
A2M	0.013	0.13	-9999	-1.5	8	8
CEBPB	0.016	0.007	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.044	0.093	-9999	-0.54	6	6
STAT3	-0.091	0.26	-9999	-0.77	71	71
STAT1	-0.013	0.021	-9999	-10000	0	0
CEBPD	-0.067	0.22	-9999	-0.64	63	63
PIK3CA	0.012	0.009	-9999	-0.29	1	1
PI3K	-0.008	0.067	-9999	-0.6	14	14
JUN	-0.005	0.063	-9999	-0.79	7	7
PIAS3/MITF	-0.16	0.22	-9999	-0.72	85	85
MAPK11	-0.13	0.25	-9999	-0.73	97	97
STAT3 (dimer)/FOXO1	-0.036	0.22	-9999	-0.59	68	68
GRB2/SOS1/GAB family	-0.14	0.2	-9999	-0.71	72	72
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.16	0.26	-9999	-0.46	283	283
GRB2	0.008	0.011	-9999	-0.29	1	1
JAK2	-0.001	0.024	-9999	-0.79	1	1
LBP	-0.24	0.45	-9999	-0.95	286	286
PIK3R1	0.002	0.09	-9999	-0.79	14	14
JAK1	0.009	0.025	-9999	-0.79	1	1
MYC	-0.078	0.26	-9999	-0.8	69	69
FGG	-0.075	0.22	-9999	-0.63	63	63
macrophage differentiation	-0.084	0.24	-9999	-0.71	71	71
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.23	0.28	-9999	-0.5	504	504
JUNB	-0.064	0.21	-9999	-0.6	64	64
FOS	-0.24	0.36	-9999	-0.79	329	329
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.15	0.26	-9999	-0.47	283	283
STAT1/PIAS1	-0.13	0.23	-9999	-0.47	211	211
GRB2/SOS1/GAB family/SHP2/PI3K	0.002	0.037	-9999	-0.29	5	5
STAT3 (dimer)	-0.087	0.25	-9999	-0.74	71	71
PRKCD	-0.061	0.22	-9999	-0.61	77	77
IL6R	-0.022	0.16	-9999	-0.79	44	44
SOCS3	-0.12	0.24	-9999	-0.74	87	87
gp130 (dimer)/JAK1/JAK1/LMO4	-0.057	0.18	-9999	-0.52	140	140
Rac1/GTP	-0.15	0.21	-9999	-0.67	91	91
HCK	-0.004	0.033	-9999	-10000	0	0
MAPKKK cascade	-0.006	0.084	-9999	-1	2	2
bone resorption	-0.072	0.21	-9999	-0.61	57	57
IRF1	-0.066	0.22	-9999	-0.65	51	51
mol:GDP	-0.13	0.25	-9999	-0.55	159	159
SOS1	0	0.003	-9999	-10000	0	0
VAV1	-0.13	0.25	-9999	-0.6	136	136
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.16	0.25	-9999	-0.8	92	92
PTPN11	-0.013	0.019	-9999	-10000	0	0
IL6/IL6RA	-0.24	0.31	-9999	-0.62	419	419
gp130 (dimer)/TYK2/TYK2/LMO4	-0.06	0.18	-9999	-0.51	140	140
gp130 (dimer)/JAK2/JAK2/LMO4	-0.06	0.18	-9999	-0.52	140	140
IL6	-0.28	0.38	-9999	-0.78	401	401
PIAS3	0	0	-9999	-10000	0	0
PTPRE	0.003	0.035	-9999	-0.79	2	2
PIAS1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.18	0.24	-9999	-0.4	503	503
LMO4	0.009	0.049	-9999	-0.44	10	10
STAT3 (dimer)/PIAS3	-0.15	0.21	-9999	-0.78	70	70
MCL1	0.05	0.035	-9999	-10000	0	0

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.023	0.062	-9999	-0.56	11	11
alphaM/beta2 Integrin/GPIbA	-0.024	0.057	-9999	-0.52	9	9
alphaM/beta2 Integrin/proMMP-9	-0.083	0.082	-9999	-0.39	8	8
PLAUR	-0.023	0.079	-9999	-0.29	86	86
HMGB1	-0.013	0.017	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.017	0.029	-9999	-10000	0	0
AGER	-0.015	0.04	-9999	-0.66	3	3
RAP1A	0	0	-9999	-10000	0	0
SELPLG	0	0	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.074	0.096	-9999	-0.46	6	6
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.13	0.15	-9999	-0.29	483	483
CYR61	-0.043	0.18	-9999	-0.79	59	59
TLN1	0	0	-9999	-10000	0	0
Rap1/GTP	-0.057	0.11	-9999	-0.52	22	22
RHOA	0	0	-9999	-10000	0	0
P-selectin oligomer	-0.18	0.33	-9999	-0.79	257	257
MYH2	-0.07	0.16	-9999	-0.41	111	111
MST1R	-0.011	0.083	-9999	-0.55	21	21
leukocyte activation during inflammatory response	-0.29	0.22	-9999	-0.46	668	668
APOB	-0.48	0.38	-9999	-0.79	668	668
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.008	0.079	-9999	-0.75	12	12
JAM3	-0.005	0.063	-9999	-0.79	7	7
GP1BA	-0.012	0.077	-9999	-0.4	33	33
alphaM/beta2 Integrin/CTGF	-0.025	0.071	-9999	-0.57	15	15
alphaM/beta2 Integrin	-0.071	0.13	-9999	-0.35	107	107
JAM3 homodimer	-0.005	0.063	-9999	-0.79	7	7
ICAM2	-0.004	0.053	-9999	-0.79	5	5
ICAM1	-0.004	0.035	-9999	-0.29	16	16
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.061	0.14	-9999	-0.3	202	202
cell adhesion	-0.024	0.057	-9999	-0.52	9	9
NFKB1	-0.096	0.21	-9999	-0.66	15	15
THY1	-0.002	0.025	-9999	-0.29	8	8
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.33	0.26	-9999	-0.53	668	668
alphaM/beta2 Integrin/LRP/tPA	-0.034	0.11	-9999	-0.54	46	46
IL6	-0.3	0.48	-9999	-0.93	400	400
ITGB2	-0.017	0.039	-9999	-0.3	16	16
elevation of cytosolic calcium ion concentration	-0.025	0.049	-9999	-0.36	2	2
alphaM/beta2 Integrin/JAM2/JAM3	-0.044	0.13	-9999	-0.53	68	68
JAM2	-0.048	0.19	-9999	-0.79	66	66
alphaM/beta2 Integrin/ICAM1	-0.022	0.08	-9999	-0.53	21	21
alphaM/beta2 Integrin/uPA/Plg	-0.019	0.033	-9999	-10000	0	0
RhoA/GTP	-0.088	0.16	-9999	-0.38	199	199
positive regulation of phagocytosis	-0.049	0.089	-9999	-0.45	19	19
Ron/MSP	-0.016	0.098	-9999	-0.66	22	22
alphaM/beta2 Integrin/uPAR/uPA	-0.025	0.05	-9999	-0.36	2	2
alphaM/beta2 Integrin/uPAR	-0.029	0.048	-9999	-0.34	4	4
PLAU	-0.007	0.045	-9999	-0.29	27	27
PLAT	-0.028	0.14	-9999	-0.74	41	41
actin filament polymerization	-0.066	0.15	-9999	-0.39	112	112
MST1	-0.012	0.089	-9999	-0.58	22	22
alphaM/beta2 Integrin/lipoprotein(a)	-0.29	0.22	-9999	-0.47	668	668
TNF	-0.087	0.22	-9999	-0.96	17	17
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.021	0.036	-9999	-10000	0	0
fibrinolysis	-0.019	0.032	-9999	-10000	0	0
HCK	-0.004	0.033	-9999	-10000	0	0
dendritic cell antigen processing and presentation	-0.061	0.14	-9999	-0.3	202	202
VTN	-0.027	0.1	-9999	-0.34	88	88
alphaM/beta2 Integrin/CYR61	-0.046	0.13	-9999	-0.57	59	59
LPA	-0.001	0.02	-9999	-0.29	5	5
LRP1	-0.009	0.085	-9999	-0.79	13	13
cell migration	-0.073	0.084	-9999	-0.47	16	16
FN1	-0.12	0.14	-9999	-0.29	431	431
alphaM/beta2 Integrin/Thy1	-0.018	0.031	-9999	-10000	0	0
MPO	-0.051	0.19	-9999	-0.77	72	72
KNG1	-0.006	0.041	-9999	-10000	0	0
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.065	0.16	-9999	-0.4	120	120
ELA2	0	0	-9999	-10000	0	0
PLG	-0.002	0.025	-9999	-0.29	8	8
CTGF	-0.012	0.093	-9999	-0.7	18	18
alphaM/beta2 Integrin/Hck	-0.019	0.035	-9999	-0.33	2	2
ITGAM	-0.015	0.028	-9999	-0.35	2	2
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.13	0.21	-9999	-0.5	257	257
HP	-0.16	0.31	-9999	-0.71	244	244
leukocyte adhesion	-0.076	0.13	-9999	-0.58	46	46
SELP	-0.18	0.33	-9999	-0.79	257	257

×

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	-0.005	0.048	-9999	-0.6	6	6
alphaV beta3 Integrin	-0.23	0.28	-9999	-0.54	459	459
PTK2	-0.089	0.19	-9999	-0.68	42	42
IGF1R	-0.02	0.12	-9999	-0.6	36	36
PI4KB	0	0	-9999	-10000	0	0
MFGE8	-0.012	0.091	-9999	-0.62	21	21
SRC	0	0.009	-9999	-0.29	1	1
CDKN1B	-0.088	0.12	-9999	-0.88	11	11
VEGFA	-0.003	0.031	-9999	-0.29	12	12
ILK	-0.086	0.12	-9999	-0.83	8	8
ROCK1	-0.001	0.024	-9999	-0.79	1	1
AKT1	-0.076	0.1	-9999	-0.77	8	8
PTK2B	-0.019	0.095	-9999	-0.49	38	38
alphaV/beta3 Integrin/JAM-A	-0.2	0.24	-9999	-0.47	463	463
CBL	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.019	0.095	-9999	-0.52	37	37
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.14	0.25	-9999	-0.54	271	271
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.013	0.062	-9999	-0.53	7	7
alphaV/beta3 Integrin/Syndecan-1	-0.028	0.1	-9999	-0.53	38	38
PI4KA	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.33	0.35	-9999	-0.76	354	354
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
alphaV/beta3 Integrin/Osteopontin	-0.056	0.11	-9999	-0.54	37	37
RPS6KB1	-0.3	0.32	-9999	-0.69	355	355
TLN1	0	0	-9999	-10000	0	0
MAPK3	-0.33	0.39	-9999	-0.76	459	459
GPR124	-0.009	0.085	-9999	-0.79	13	13
MAPK1	-0.33	0.39	-9999	-0.76	459	459
PXN	0	0	-9999	-10000	0	0
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
alphaV/beta3 Integrin/Tumstatin	-0.1	0.21	-9999	-0.53	214	214
cell adhesion	-0.023	0.11	-9999	-0.51	47	47
ANGPTL3	-0.001	0.018	-9999	-0.29	4	4
VEGFR2 homodimer/VEGFA homodimer/Src	-0.005	0.041	-9999	-0.52	6	6
IGF-1R heterotetramer	-0.02	0.12	-9999	-0.59	36	36
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	-0.035	0.16	-9999	-0.79	49	49
ITGB3	-0.028	0.14	-9999	-0.79	37	37
IGF1	-0.18	0.33	-9999	-0.79	247	247
RAC1	0	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.024	0.12	-9999	-0.59	43	43
apoptosis	0	0	-9999	-10000	0	0
CD47	-0.001	0.024	-9999	-0.79	1	1
alphaV/beta3 Integrin/CD47	-0.018	0.095	-9999	-0.52	38	38
VCL	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.05	0.18	-9999	-0.65	80	80
CSF1	-0.006	0.071	-9999	-0.79	9	9
PIK3C2A	-0.087	0.12	-9999	-0.85	9	9
PI4 Kinase/Pyk2	-0.17	0.21	-9999	-0.6	76	76
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.02	0.1	-9999	-0.53	38	38
FAK1/Vinculin	-0.064	0.16	-9999	-0.51	42	42
alphaV beta3/Integrin/ppsTEM5	-0.024	0.12	-9999	-0.59	43	43
RHOA	0	0	-9999	-10000	0	0
VTN	-0.027	0.1	-9999	-0.34	88	88
BCAR1	0	0	-9999	-10000	0	0
FGF2	-0.32	0.39	-9999	-0.79	446	446
F11R	-0.23	0.31	-9999	-0.6	446	446
alphaV/beta3 Integrin/Lactadherin	-0.025	0.12	-9999	-0.57	46	46
alphaV/beta3 Integrin/TGFBR2	-0.04	0.16	-9999	-0.66	66	66
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.004	0.042	-9999	-0.47	9	9
HSP90AA1	0	0.009	-9999	-0.29	1	1
alphaV/beta3 Integrin/Talin	-0.017	0.086	-9999	-0.48	37	37
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.12	0.14	-9999	-0.29	431	431
alphaV/beta3 Integrin/Pyk2	-0.019	0.096	-9999	-0.5	38	38
SDC1	-0.02	0.076	-9999	-0.3	73	73
VAV3	-0.008	0.054	-9999	-0.44	16	16
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.032	0.16	-9999	-0.79	45	45
FAK1/Paxillin	-0.064	0.16	-9999	-0.51	42	42
cell migration	-0.05	0.14	-9999	-0.45	40	40
ITGAV	0	0	-9999	-10000	0	0
PI3K	-0.19	0.23	-9999	-0.67	74	74
SPP1	-0.077	0.13	-9999	-0.29	288	288
KDR	-0.004	0.058	-9999	-0.79	6	6
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0	0	-9999	-10000	0	0
COL4A3	-0.13	0.29	-9999	-0.78	187	187
angiogenesis	-0.3	0.39	-9999	-0.74	459	459
Rac1/GTP	-0.007	0.049	-9999	-0.4	16	16
EDIL3	-0.052	0.19	-9999	-0.7	81	81
cell proliferation	-0.04	0.16	-9999	-0.65	66	66

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.096	0.2	0.63	121	-10000	0	121
KIRREL	-0.079	0.25	-10000	0	-0.79	121	121
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.096	0.2	-10000	0	-0.63	121	121
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	-0.07	0.15	-10000	0	-0.48	121	121
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.043	0.11	-10000	0	-0.36	121	121
FYN	-0.065	0.14	-10000	0	-0.46	121	121
mol:Ca2+	-0.069	0.15	-10000	0	-0.47	121	121
mol:DAG	-0.069	0.15	-10000	0	-0.48	121	121
NPHS2	-0.008	0.031	-10000	0	-0.29	5	5
mol:IP3	-0.069	0.15	-10000	0	-0.48	121	121
regulation of endocytosis	-0.055	0.14	-10000	0	-0.43	121	121
Nephrin/NEPH1/podocin/Cholesterol	-0.072	0.15	-10000	0	-0.49	121	121
establishment of cell polarity	-0.096	0.2	-10000	0	-0.63	121	121
Nephrin/NEPH1/podocin/NCK1-2	-0.062	0.14	-10000	0	-0.44	121	121
Nephrin/NEPH1/beta Arrestin2	-0.056	0.14	-10000	0	-0.43	121	121
NPHS1	-0.047	0.11	-10000	0	-0.36	17	17
Nephrin/NEPH1/podocin	-0.065	0.14	-10000	0	-0.46	121	121
TJP1	-0.001	0.024	-10000	0	-0.79	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	-0.07	0.15	-10000	0	-0.48	121	121
CD2AP	0	0.009	-10000	0	-0.29	1	1
Nephrin/NEPH1/podocin/GRB2	-0.07	0.15	-10000	0	-0.48	121	121
GRB2	0	0.009	-10000	0	-0.29	1	1
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.057	0.18	-10000	0	-0.5	130	130
cytoskeleton organization	-0.055	0.14	-10000	0	-0.44	121	121
Nephrin/NEPH1	-0.069	0.15	-10000	0	-0.47	121	121
Nephrin/NEPH1/ZO-1	-0.076	0.16	-10000	0	-0.52	121	121

×

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	-0.05	0.15	-9999	-0.53	103	103
EFNA5	-0.074	0.23	-9999	-0.78	104	104
FYN	-0.026	0.15	-9999	-0.48	104	104
neuron projection morphogenesis	-0.05	0.15	-9999	-0.53	103	103
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.051	0.16	-9999	-0.53	103	103
EPHA5	-0.001	0.02	-9999	-0.29	5	5

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	-0.005	0.049	-9999	-0.61	6	6
PDGFRB	0.005	0.049	-9999	-0.79	4	4
SPHK1	-0.025	0.055	-9999	-1.1	2	2
mol:S1P	-0.031	0.057	-9999	-0.97	2	2
S1P1/S1P/Gi	-0.1	0.23	-9999	-0.39	380	380
GNAO1	-0.023	0.14	-9999	-0.5	67	67
PDGFB-D/PDGFRB/PLCgamma1	-0.12	0.18	-9999	-0.59	77	77
PLCG1	-0.091	0.22	-9999	-0.56	99	99
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.005	0.049	-9999	-0.79	4	4
GNAI2	0.008	0.006	-9999	-10000	0	0
GNAI3	0.008	0.006	-9999	-10000	0	0
GNAI1	-0.038	0.19	-9999	-0.8	62	62
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.005	0.046	-9999	-0.54	6	6
S1P1/S1P	-0.044	0.075	-9999	-0.58	8	8
negative regulation of cAMP metabolic process	-0.098	0.22	-9999	-0.38	380	380
MAPK3	-0.16	0.31	-9999	-0.57	370	370
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	-0.004	0.059	-9999	-0.8	6	6
PLCB2	-0.008	0.086	-9999	-0.5	9	9
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.038	0.061	-9999	-0.48	8	8
receptor internalization	-0.043	0.07	-9999	-0.53	8	8
PTGS2	-0.33	0.55	-9999	-1.1	370	370
Rac1/GTP	-0.038	0.061	-9999	-0.48	8	8
RHOA	0	0	-9999	-10000	0	0
VEGFA	-0.003	0.031	-9999	-0.29	12	12
negative regulation of T cell proliferation	-0.098	0.22	-9999	-0.38	380	380
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.001	0.077	-9999	-0.79	10	10
MAPK1	-0.16	0.31	-9999	-0.57	370	370
S1P1/S1P/PDGFB-D/PDGFRB	-0.021	0.11	-9999	-0.64	10	10
ABCC1	0	0	-9999	-10000	0	0

×

Signaling events mediated by PRL

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
CCNE1	-0.06	0.12	-9999	-0.29	223	223
mol:Halofuginone	0	0.003	-9999	-10000	0	0
ITGA1	-0.008	0.079	-9999	-0.79	11	11
CDKN1A	-0.057	0.087	-9999	-0.84	2	2
PRL-3/alpha Tubulin	-0.002	0.018	-9999	-10000	0	0
mol:Ca2+	-0.033	0.096	-9999	-0.61	15	15
AGT	-0.047	0.13	-9999	-0.34	151	151
CCNA2	-0.16	0.24	-9999	-0.49	347	347
TUBA1B	0	0	-9999	-10000	0	0
EGR1	-0.17	0.29	-9999	-0.6	347	347
CDK2/Cyclin E1	-0.067	0.09	-9999	-0.81	2	2
MAPK3	0.021	0.02	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0.006	-9999	-10000	0	0
MAPK1	0.021	0.02	-9999	-10000	0	0
PTP4A1	-0.12	0.23	-9999	-0.46	347	347
PTP4A3	-0.003	0.028	-9999	-0.29	10	10
PTP4A2	0	0.009	-9999	-0.29	1	1
ITGB1	0.021	0.02	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
RAC1	-0.055	0.081	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.14	0.2	-9999	-0.42	347	347
RABGGTA	0	0	-9999	-10000	0	0
BCAR1	0.001	0.009	-9999	-10000	0	0
RHOC	-0.055	0.081	-9999	-10000	0	0
RHOA	-0.055	0.081	-9999	-10000	0	0
cell motility	-0.034	0.1	-9999	-0.24	1	1
PRL-1/alpha Tubulin	-0.13	0.2	-9999	-0.42	347	347
PRL-3/alpha1 Integrin	-0.008	0.062	-9999	-0.6	11	11
ROCK1	-0.034	0.1	-9999	-0.24	1	1
RABGGTB	0	0	-9999	-10000	0	0
CDK2	0	0	-9999	-10000	0	0
mitosis	-0.12	0.23	-9999	-0.45	347	347
ATF5	-0.001	0.018	-9999	-0.29	4	4

×

Syndecan-3-mediated signaling events

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
CTTN	-0.002	0.026	-9999	-0.29	9	9
Syndecan-3/Src/Cortactin	-0.18	0.2	-9999	-0.4	478	478
Syndecan-3/Neurocan	-0.007	0.028	-9999	-10000	0	0
POMC	-0.024	0.12	-9999	-0.79	22	22
EGFR	-0.29	0.38	-9999	-0.78	410	410
Syndecan-3/EGFR	-0.16	0.21	-9999	-0.44	405	405
AGRP	-0.003	0.028	-9999	-0.29	10	10
NCSTN	0	0	-9999	-10000	0	0
PSENEN	-0.001	0.013	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	-0.001	0.024	-9999	-0.79	1	1
APH1A	0	0	-9999	-10000	0	0
NCAN	-0.019	0.073	-9999	-0.29	72	72
long-term memory	-0.002	0.02	-9999	-0.41	2	2
Syndecan-3/IL8	-0.016	0.066	-9999	-0.44	22	22
PSEN1	0	0	-9999	-10000	0	0
Src/Cortactin	-0.002	0.018	-9999	-10000	0	0
FYN	-0.001	0.034	-9999	-0.79	2	2
limb bud formation	0	0.003	-9999	-10000	0	0
MC4R	-0.003	0.032	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
PTN	-0.34	0.39	-9999	-0.78	480	480
FGFR/FGF/Syndecan-3	0	0.003	-9999	-10000	0	0
neuron projection morphogenesis	-0.17	0.19	-9999	-0.39	478	478
Syndecan-3/AgRP	-0.001	0.011	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	-0.002	0.015	-9999	-10000	0	0
Fyn/Cortactin	-0.003	0.031	-9999	-0.6	2	2
SDC3	0	0.003	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.015	0.065	-9999	-0.43	22	22
IL8	-0.033	0.13	-9999	-0.42	87	87
Syndecan-3/Fyn/Cortactin	-0.002	0.02	-9999	-0.42	2	2
Syndecan-3/CASK	0	0.003	-9999	-10000	0	0
alpha-MSH/MC4R	-0.02	0.094	-9999	-0.6	24	24
Gamma Secretase	-0.001	0.014	-9999	-0.44	1	1

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.052	0.2	-9999	-0.8	74	74
PDGF/PDGFRA/CRKL	-0.041	0.15	-9999	-0.6	73	73
positive regulation of JUN kinase activity	-0.031	0.12	-9999	-0.46	73	73
CRKL	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.044	0.15	-9999	-0.61	73	73
AP1	-0.36	0.54	-9999	-1.2	329	329
mol:IP3	-0.035	0.16	-9999	-0.63	73	73
PLCG1	-0.035	0.16	-9999	-0.63	73	73
PDGF/PDGFRA/alphaV Integrin	-0.041	0.15	-9999	-0.6	73	73
RAPGEF1	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
mol:Ca2+	-0.035	0.16	-9999	-0.63	73	73
CAV3	-0.001	0.015	-9999	-0.29	3	3
CAV1	-0.17	0.33	-9999	-0.79	241	241
SHC/Grb2/SOS1	-0.031	0.12	-9999	-0.46	73	73
PDGF/PDGFRA/Shf	-0.041	0.15	-9999	-0.61	73	73
FOS	-0.32	0.55	-9999	-1.1	329	329
JUN	-0.024	0.059	-9999	-0.67	7	7
oligodendrocyte development	-0.04	0.15	-9999	-0.6	73	73
GRB2	0	0.009	-9999	-0.29	1	1
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
mol:DAG	-0.035	0.16	-9999	-0.63	73	73
PDGF/PDGFRA	-0.052	0.2	-9999	-0.8	74	74
actin cytoskeleton reorganization	-0.041	0.15	-9999	-0.6	74	74
SRF	0.015	0.022	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
PI3K	-0.041	0.15	-9999	-0.54	83	83
PDGF/PDGFRA/Crk/C3G	-0.035	0.13	-9999	-0.52	73	73
JAK1	-0.025	0.16	-9999	-0.6	74	74
ELK1/SRF	-0.027	0.12	-9999	-0.47	73	73
SHB	-0.001	0.025	-9999	-0.54	2	2
SHF	-0.001	0.027	-9999	-0.46	3	3
CSNK2A1	0.019	0.027	-9999	-10000	0	0
GO:0007205	-0.037	0.17	-9999	-0.65	73	73
SOS1	0	0	-9999	-10000	0	0
Ras protein signal transduction	-0.031	0.12	-9999	-0.46	73	73
PDGF/PDGFRA/SHB	-0.041	0.15	-9999	-0.6	74	74
PDGF/PDGFRA/Caveolin-1	-0.17	0.32	-9999	-0.7	266	266
ITGAV	0	0	-9999	-10000	0	0
ELK1	-0.035	0.16	-9999	-0.59	73	73
PIK3CA	0	0.009	-9999	-0.29	1	1
PDGF/PDGFRA/Crk	-0.041	0.15	-9999	-0.6	73	73
JAK-STAT cascade	-0.025	0.16	-9999	-0.6	74	74
cell proliferation	-0.041	0.15	-9999	-0.61	73	73

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.017	0.031	-9999	-10000	0	0
VDR	0	0	-9999	-10000	0	0
FAM120B	0	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.034	0.16	-9999	-0.42	19	19
RXRs/LXRs/DNA/Oxysterols	-0.014	0.14	-9999	-0.49	19	19
MED1	-0.006	0.043	-9999	-0.29	24	24
mol:9cRA	0.005	0.008	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.024	0.092	-9999	-0.35	72	72
RXRs/NUR77	-0.16	0.24	-9999	-0.5	337	337
RXRs/PPAR	-0.13	0.23	-9999	-0.51	165	165
NCOR2	0	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0	0	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	-0.008	0.054	-9999	-0.45	15	15
RARA	-0.004	0.035	-9999	-0.29	16	16
NCOA1	-0.001	0.024	-9999	-0.79	1	1
VDR/VDR/DNA	0	0	-9999	-10000	0	0
RARs/RARs/DNA/9cRA	-0.008	0.055	-9999	-0.46	15	15
RARG	0	0	-9999	-10000	0	0
RPS6KB1	0.029	0.052	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.023	0.088	-9999	-0.34	72	72
THRA	-0.001	0.024	-9999	-0.79	1	1
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0	0	-9999	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.2	-9999	-0.46	268	268
NR1H4	-0.003	0.032	-9999	-0.29	13	13
RXRs/LXRs/DNA	-0.1	0.18	-9999	-0.42	268	268
NR1H2	0.016	0.006	-9999	-10000	0	0
NR1H3	0.016	0.007	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.11	0.19	-9999	-0.44	268	268
NR4A1	-0.071	0.23	-9999	-0.79	99	99
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.043	0.13	-9999	-0.27	268	268
RXRG	-0.18	0.34	-9999	-0.78	268	268
RXR alpha/CCPG	0	0	-9999	-10000	0	0
RXRA	0.016	0.006	-9999	-10000	0	0
RXRB	0.016	0.007	-9999	-10000	0	0
THRB	-0.044	0.18	-9999	-0.79	61	61
PPARG	-0.19	0.34	-9999	-0.79	268	268
PPARD	0	0	-9999	-10000	0	0
TNF	-0.014	0.18	-9999	-1.2	14	14
mol:Oxysterols	0.005	0.007	-9999	-10000	0	0
cholesterol transport	-0.014	0.14	-9999	-0.48	19	19
PPARA	-0.006	0.067	-9999	-0.79	8	8
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.011	0.092	-9999	-0.79	15	15
RXRs/NUR77/BCL2	-0.12	0.19	-9999	-0.37	359	359
SREBF1	-0.005	0.14	-9999	-0.68	5	5
RXRs/RXRs/DNA/9cRA	-0.12	0.2	-9999	-0.46	268	268
ABCA1	-0.008	0.16	-9999	-1.1	10	10
RARs/THRs	-0.032	0.12	-9999	-0.47	72	72
RXRs/FXR	-0.11	0.2	-9999	-0.47	268	268
BCL2	-0.027	0.14	-9999	-0.79	37	37

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.054	0.3	-10000	0	-0.81	131	131
IHH	-0.014	0.082	-10000	0	-0.42	9	9
SHH Np/Cholesterol/GAS1	-0.032	0.12	-10000	0	-0.49	66	66
LRPAP1	0	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.032	0.12	0.48	66	-10000	0	66
SMO/beta Arrestin2	-0.076	0.23	-10000	0	-0.84	82	82
SMO	-0.036	0.26	-10000	0	-0.89	85	85
AKT1	0.006	0.12	-10000	0	-0.48	23	23
ARRB2	0	0	-10000	0	-10000	0	0
BOC	-0.058	0.21	-10000	0	-0.79	81	81
ADRBK1	0	0	-10000	0	-10000	0	0
heart looping	-0.035	0.26	-10000	0	-0.84	90	90
STIL	-0.039	0.21	-10000	0	-0.7	86	86
DHH N/PTCH2	-0.061	0.19	-10000	0	-0.63	104	104
DHH N/PTCH1	-0.09	0.24	-10000	0	-0.74	116	116
PIK3CA	0	0.009	-10000	0	-0.29	1	1
DHH	-0.022	0.13	-10000	0	-0.79	30	30
PTHLH	-0.081	0.38	-10000	0	-1.1	131	131
determination of left/right symmetry	-0.035	0.26	-10000	0	-0.84	90	90
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
skeletal system development	-0.079	0.37	-10000	0	-1	131	131
IHH N/Hhip	-0.009	0.051	-10000	0	-0.53	3	3
DHH N/Hhip	-0.019	0.1	-10000	0	-0.61	32	32
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.035	0.26	-10000	0	-0.84	90	90
pancreas development	-0.003	0.041	-10000	0	-0.4	9	9
HHAT	-0.001	0.024	-10000	0	-0.79	1	1
PI3K	-0.008	0.068	-10000	0	-0.6	14	14
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.047	0.19	-10000	0	-0.79	65	65
somite specification	-0.035	0.26	-10000	0	-0.84	90	90
SHH Np/Cholesterol/PTCH1	-0.071	0.2	-10000	0	-0.71	91	91
SHH Np/Cholesterol/PTCH2	-0.039	0.13	-10000	0	-0.48	82	82
SHH Np/Cholesterol/Megalin	-0.14	0.21	-10000	0	-0.48	292	292
SHH	0.01	0.035	-10000	0	-0.61	1	1
catabolic process	-0.047	0.26	-10000	0	-0.82	97	97
SMO/Vitamin D3	-0.075	0.22	-10000	0	-0.81	83	83
SHH Np/Cholesterol/Hhip	-0.005	0.035	-10000	0	-0.49	3	3
LRP2	-0.22	0.35	-10000	0	-0.74	318	318
receptor-mediated endocytosis	-0.15	0.25	-10000	0	-0.82	99	99
SHH Np/Cholesterol/BOC	-0.039	0.13	-10000	0	-0.49	82	82
SHH Np/Cholesterol/CDO	-0.009	0.059	-10000	0	-0.48	15	15
mesenchymal cell differentiation	0.005	0.035	0.48	3	-10000	0	3
mol:Vitamin D3	-0.03	0.22	-10000	0	-0.71	93	93
IHH N/PTCH2	-0.055	0.18	-10000	0	-0.66	85	85
CDON	-0.01	0.089	-10000	0	-0.79	14	14
IHH N/PTCH1	-0.045	0.26	-10000	0	-0.83	97	97
Megalin/LRPAP1	-0.16	0.26	-10000	0	-0.6	291	291
PTCH2	-0.058	0.21	-10000	0	-0.79	81	81
SHH Np/Cholesterol	-0.003	0.025	-10000	0	-0.49	1	1
PTCH1	-0.047	0.26	-10000	0	-0.82	97	97
HHIP	-0.003	0.041	-10000	0	-0.4	9	9

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.053	0.2	-10000	0	-0.78	74	74
HRAS	-0.003	0.028	-10000	0	-0.29	10	10
EGFR	-0.29	0.38	-10000	0	-0.78	410	410
AKT	0.013	0.084	-10000	0	-0.57	20	20
FOXO3	-0.002	0.041	-10000	0	-0.79	3	3
AKT1	0	0	-10000	0	-10000	0	0
FOXO1	-0.009	0.082	-10000	0	-0.79	12	12
AKT3	-0.014	0.11	-10000	0	-0.79	20	20
FOXO4	0	0	-10000	0	-10000	0	0
MET	-0.14	0.3	-10000	0	-0.78	189	189
PIK3CA	0	0.009	-10000	0	-0.29	1	1
PIK3CB	0	0	-10000	0	-10000	0	0
NRAS	-0.001	0.013	-10000	0	-0.29	2	2
PIK3CG	-0.013	0.099	-10000	0	-0.69	21	21
PIK3R3	0	0.009	-10000	0	-0.29	1	1
PIK3R2	0	0	-10000	0	-10000	0	0
NF1	-0.001	0.024	-10000	0	-0.79	1	1
RAS	-0.095	0.16	0.25	1	-0.26	453	454
ERBB2	-0.024	0.083	-10000	0	-0.3	89	89
proliferation/survival/translation	-0.004	0.059	0.28	14	-10000	0	14
PI3K	-0.087	0.16	-10000	0	-0.26	420	420
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
FOXO	0.027	0.029	-10000	0	-0.49	1	1
AKT2	0	0	-10000	0	-10000	0	0
PTEN	-0.001	0.034	-10000	0	-0.79	2	2

×

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	-0.009	0.053	-10000	0	-0.42	14	14
adherens junction organization	0.032	0.061	-10000	0	-0.3	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.14	0.18	-10000	0	-0.37	412	412
FMN1	0.025	0.086	-10000	0	-0.44	21	21
mol:IP3	-0.009	0.05	-10000	0	-0.39	14	14
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.01	0.052	-10000	0	-0.31	29	29
CTNNB1	0.001	0.004	-10000	0	-10000	0	0
AKT1	-0.01	0.051	-10000	0	-0.38	14	14
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.013	0.079	-10000	0	-0.5	28	28
CTNND1	0.011	0.009	-10000	0	-0.29	1	1
mol:PI-4-5-P2	0.033	0.055	-10000	0	-10000	0	0
VASP	0.033	0.056	-10000	0	-10000	0	0
ZYX	0.033	0.056	-10000	0	-10000	0	0
JUB	0.032	0.062	-10000	0	-0.41	4	4
EGFR(dimer)	-0.16	0.21	-10000	0	-0.42	406	406
E-cadherin/beta catenin-gamma catenin	-0.013	0.081	-10000	0	-0.5	29	29
mol:PI-3-4-5-P3	-0.01	0.055	-10000	0	-0.4	14	14
PIK3CA	0.011	0.009	-10000	0	-0.29	1	1
PI3K	-0.011	0.056	-10000	0	-0.41	14	14
FYN	0.04	0.055	-10000	0	-0.34	16	16
mol:Ca2+	-0.009	0.049	-10000	0	-0.38	14	14
JUP	0	0.026	-10000	0	-0.54	2	2
PIK3R1	0.001	0.09	-10000	0	-0.79	14	14
mol:DAG	-0.009	0.05	-10000	0	-0.39	14	14
CDH1	-0.02	0.12	-10000	0	-0.79	28	28
RhoA/GDP	-0.14	0.18	-10000	0	-0.37	412	412
establishment of polarity of embryonic epithelium	0.033	0.055	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-0.29	1	1
RAC1	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
EGFR	-0.29	0.38	-10000	0	-0.78	410	410
CASR	0.033	0.056	-10000	0	-0.36	14	14
RhoA/GTP	-0.008	0.044	-10000	0	-0.34	14	14
AKT2	-0.01	0.051	-10000	0	-0.38	14	14
actin cable formation	0.032	0.084	-10000	0	-0.42	21	21
apoptosis	0.01	0.052	0.39	14	-10000	0	14
CTNNA1	0.012	0.002	-10000	0	-10000	0	0
mol:GDP	-0.15	0.2	-10000	0	-0.4	412	412
PIP5K1A	0.033	0.056	-10000	0	-10000	0	0
PLCG1	-0.009	0.051	-10000	0	-0.4	14	14
Rac1/GTP	-0.15	0.19	-10000	0	-0.39	406	406
homophilic cell adhesion	0.001	0.002	-10000	0	-10000	0	0

×

LPA receptor mediated events

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
GNB1/GNG2	-0.019	0.097	-9999	-0.51	37	37
NF kappa B1 p50/RelA/I kappa B alpha	-0.043	0.11	-9999	-0.46	6	6
AP1	-0.19	0.25	-9999	-0.47	423	423
mol:PIP3	-0.2	0.24	-9999	-0.7	123	123
AKT1	-0.016	0.078	-9999	-0.59	10	10
PTK2B	0.014	0.062	-9999	-0.29	26	26
RHOA	0.028	0.028	-9999	-10000	0	0
PIK3CB	0	0	-9999	-10000	0	0
mol:Ca2+	-0.007	0.13	-9999	-0.35	128	128
MAGI3	-0.001	0.034	-9999	-0.79	2	2
RELA	0	0	-9999	-10000	0	0
apoptosis	-0.062	0.15	-9999	-0.42	147	147
HRAS/GDP	-0.002	0.019	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.019	0.14	-9999	-0.4	122	122
NF kappa B1 p50/RelA	-0.053	0.14	-9999	-0.63	10	10
endothelial cell migration	0.007	0.12	-9999	-0.63	34	34
ADCY4	-0.004	0.15	-9999	-0.63	41	41
ADCY5	-0.071	0.19	-9999	-0.59	82	82
ADCY6	0.006	0.13	-9999	-0.6	31	31
ADCY7	0.006	0.13	-9999	-0.6	31	31
ADCY1	-0.003	0.14	-9999	-0.64	37	37
ADCY2	-0.015	0.16	-9999	-0.62	49	49
ADCY3	0.006	0.13	-9999	-0.6	31	31
ADCY8	0.003	0.13	-9999	-0.61	31	31
ADCY9	0.006	0.13	-9999	-0.6	31	31
GSK3B	0.021	0.059	-9999	-0.35	10	10
arachidonic acid secretion	0.009	0.13	-9999	-0.56	34	34
GNG2	-0.011	0.092	-9999	-0.79	15	15
TRIP6	-0.001	0.016	-9999	-0.51	1	1
GNAO1	-0.006	0.13	-9999	-0.52	56	56
HRAS	-0.003	0.028	-9999	-0.29	10	10
NFKBIA	-0.003	0.15	-9999	-0.39	128	128
GAB1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0.001	0.004	-9999	-10000	0	0
JUN	-0.005	0.063	-9999	-0.79	7	7
LPA/LPA2/NHERF2	-0.002	0.016	-9999	-10000	0	0
TIAM1	0.001	0.004	-9999	-10000	0	0
PIK3R1	-0.01	0.088	-9999	-0.79	14	14
mol:IP3	-0.007	0.13	-9999	-0.35	128	128
PLCB3	0.026	0.016	-9999	-10000	0	0
FOS	-0.24	0.36	-9999	-0.79	329	329
positive regulation of mitosis	0.009	0.13	-9999	-0.56	34	34
LPA/LPA1-2-3	-0.073	0.17	-9999	-0.49	147	147
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	-0.38	25	25
GNAZ	0.008	0.1	-9999	-0.48	43	43
EGFR/PI3K-beta/Gab1	-0.2	0.26	-9999	-0.74	123	123
positive regulation of dendritic cell cytokine production	-0.072	0.17	-9999	-0.48	147	147
LPA/LPA2/MAGI-3	-0.002	0.025	-9999	-0.52	2	2
ARHGEF1	-0.011	0.069	-9999	-0.44	24	24
GNAI2	0.013	0.087	-9999	-0.46	34	34
GNAI3	0.013	0.087	-9999	-0.46	34	34
GNAI1	-0.018	0.16	-9999	-0.53	89	89
LPA/LPA3	-0.08	0.2	-9999	-0.6	128	128
LPA/LPA2	-0.002	0.016	-9999	-10000	0	0
LPA/LPA1	-0.017	0.096	-9999	-0.54	34	34
HB-EGF/EGFR	-0.26	0.25	-9999	-0.57	405	405
HBEGF	-0.071	0.11	-9999	-0.6	3	3
mol:DAG	-0.007	0.13	-9999	-0.35	128	128
cAMP biosynthetic process	-0.012	0.15	-9999	-0.56	55	55
NFKB1	0	0	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
GNB1	0	0	-9999	-10000	0	0
LYN	-0.003	0.15	-9999	-0.46	14	14
GNAQ	-0.053	0.13	-9999	-0.41	131	131
LPAR2	-0.001	0.015	-9999	-0.29	2	2
LPAR3	-0.1	0.26	-9999	-0.79	128	128
LPAR1	-0.019	0.12	-9999	-0.79	24	24
IL8	-0.19	0.23	-9999	-0.44	432	432
PTK2	-0.066	0.16	-9999	-0.45	147	147
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.062	0.15	-9999	-0.42	147	147
EGFR	-0.29	0.38	-9999	-0.78	410	410
PLCG1	-0.029	0.15	-9999	-0.42	128	128
PLD2	-0.066	0.16	-9999	-0.45	147	147
G12/G13	-0.013	0.074	-9999	-0.48	24	24
PI3K-beta	-0.019	0.093	-9999	-0.72	10	10
cell migration	-0.021	0.053	-9999	-0.24	5	5
SLC9A3R2	-0.001	0.02	-9999	-0.29	5	5
PXN	0.002	0.1	-9999	-0.39	25	25
HRAS/GTP	-0.035	0.12	-9999	-0.58	34	34
RAC1	0	0	-9999	-10000	0	0
MMP9	-0.13	0.15	-9999	-0.29	483	483
PRKCE	0.01	0.002	-9999	-10000	0	0
PRKCD	0.001	0.12	-9999	-0.54	2	2
Gi(beta/gamma)	-0.037	0.12	-9999	-0.58	39	39
mol:LPA	-0.002	0.021	-9999	-0.22	10	10
TRIP6/p130 Cas/FAK1/Paxillin	-0.055	0.14	-9999	-0.68	9	9
MAPKKK cascade	0.009	0.13	-9999	-0.56	34	34
contractile ring contraction involved in cytokinesis	0.028	0.028	-9999	-0.23	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.057	0.14	-9999	-0.42	136	136
GNA15	-0.053	0.13	-9999	-0.41	129	129
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
MAPT	-0.021	0.15	-9999	-0.42	122	122
GNA11	-0.053	0.13	-9999	-0.41	132	132
Rac1/GTP	0.001	0.005	-9999	-10000	0	0
MMP2	0.007	0.12	-9999	-0.63	34	34

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.12	0.18	-9999	-0.39	330	330
MAP3K8	0.001	0.073	-9999	-0.74	10	10
FOS	-0.035	0.14	-9999	-0.46	41	41
PRKCA	-0.013	0.13	-9999	-0.76	31	31
PTPN7	-0.009	0.073	-9999	-0.3	63	63
HRAS	-0.003	0.028	-9999	-0.3	10	10
PRKCB	-0.011	0.12	-9999	-0.55	39	39
NRAS	-0.001	0.013	-9999	-0.3	2	2
RAS family/GTP	-0.002	0.015	-9999	-10000	0	0
MAPK3	-0.008	0.073	-9999	-0.25	35	35
MAP2K1	-0.013	0.14	-9999	-0.57	53	53
ELK1	-0.003	0.01	-9999	-0.29	1	1
BRAF	-0.033	0.12	-9999	-0.57	48	48
mol:GTP	-0.002	0.003	-9999	-0.006	329	329
MAPK1	-0.008	0.073	-9999	-0.25	35	35
RAF1	-0.033	0.12	-9999	-0.57	48	48
KRAS	-0.001	0.012	-9999	-0.29	2	2

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.029	0.031	-9999	-10000	0	0
BUB1B	-0.041	0.053	-9999	-10000	0	0
PLK1	-0.008	0.024	-9999	-10000	0	0
PLK1S1	0	0.014	-9999	-10000	0	0
KIF2A	0.002	0.021	-9999	-10000	0	0
regulation of mitotic centrosome separation	-0.008	0.024	-9999	-10000	0	0
GOLGA2	0	0	-9999	-10000	0	0
Hec1/SPC24	-0.17	0.12	-9999	-0.28	534	534
WEE1	-0.002	0.024	-9999	-10000	0	0
cytokinesis	-0.056	0.058	-9999	-0.26	21	21
PP2A-alpha B56	0.027	0.019	-9999	-10000	0	0
AURKA	0	0.015	-9999	-10000	0	0
PICH/PLK1	-0.072	0.098	-9999	-0.34	11	11
CENPE	-0.053	0.087	-9999	-0.18	179	179
RhoA/GTP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.002	0.021	-9999	-10000	0	0
PPP2CA	0	0	-9999	-10000	0	0
FZR1	0	0	-9999	-10000	0	0
TPX2	-0.006	0.017	-9999	-10000	0	0
PAK1	-0.006	0.043	-9999	-0.29	25	25
SPC24	-0.18	0.14	-9999	-0.29	689	689
FBXW11	0	0	-9999	-10000	0	0
CLSPN	-0.006	0.019	-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	-0.005	0.013	-9999	-0.052	2	2
G2 phase of mitotic cell cycle	-0.001	0.002	-9999	-10000	0	0
STAG2	-0.001	0.024	-9999	-0.79	1	1
GRASP65/GM130/RAB1/GTP	0.008	0.009	-9999	-10000	0	0
spindle elongation	-0.008	0.024	-9999	-10000	0	0
ODF2	0.002	0.004	-9999	-10000	0	0
BUB1	0.021	0.015	-9999	-10000	0	0
TPT1	0	0.014	-9999	-10000	0	0
CDC25C	-0.009	0.017	-9999	-10000	0	0
CDC25B	0.005	0.041	-9999	-0.29	20	20
SGOL1	-0.029	0.031	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.021	0.044	-9999	-10000	0	0
CDC14B	-0.01	0.11	-9999	-0.62	36	36
CDC20	-0.16	0.15	-9999	-0.29	588	588
PLK1/PBIP1	-0.028	0.053	-9999	-0.18	4	4
mitosis	-0.006	0.007	-9999	-0.022	2	2
FBXO5	0	0.023	-9999	-10000	0	0
CDC2	-0.001	0.002	-9999	-10000	0	0
NDC80	-0.18	0.14	-9999	-0.29	662	662
metaphase plate congression	-0.002	0.016	-9999	-10000	0	0
ERCC6L	-0.064	0.089	-9999	-0.29	11	11
NLP/gamma Tubulin	-0.001	0.014	-9999	-10000	0	0
microtubule cytoskeleton organization	0	0.014	-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	0.1	-9999	-0.29	274	274
GRASP65/GM130/RAB1/GTP/PLK1	-0.002	0.004	-9999	-10000	0	0
RAB1A	0	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	-0.003	0.024	-9999	-10000	0	0
mitotic prometaphase	-0.002	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.014	0.051	-9999	-0.3	25	25
microtubule-based process	-0.12	0.069	-9999	-0.18	218	218
Golgi organization	-0.008	0.024	-9999	-10000	0	0
Cohesin/SA2	-0.01	0.018	-9999	-0.45	1	1
PPP1CB/MYPT1	0	0	-9999	-10000	0	0
KIF20A	-0.22	0.13	-9999	-0.29	820	820
APC/C/CDC20	-0.088	0.081	-9999	-0.2	7	7
PPP2R1A	0	0	-9999	-10000	0	0
chromosome segregation	-0.028	0.052	-9999	-0.18	4	4
PRC1	-0.074	0.13	-9999	-0.29	275	275
ECT2	-0.004	0.039	-9999	-0.17	38	38
C13orf34	-0.001	0.022	-9999	-10000	0	0
NUDC	-0.002	0.016	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.04	0.052	-9999	-10000	0	0
spindle assembly	-0.004	0.02	-9999	-10000	0	0
spindle stabilization	0	0.014	-9999	-10000	0	0
APC/C/HCDH1	-0.017	0.094	-9999	-0.53	36	36
MKLP2/PLK1	-0.12	0.069	-9999	-0.18	218	218
CCNB1	-0.05	0.12	-9999	-0.29	221	221
PPP1CB	0	0	-9999	-10000	0	0
BTRC	0	0	-9999	-10000	0	0
ROCK2	-0.01	0.089	-9999	-0.51	32	32
TUBG1	0	0.014	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.024	0.041	-9999	-10000	0	0
MLF1IP	-0.025	0.074	-9999	-0.2	2	2
INCENP	0.002	0.004	-9999	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.003	0.048	-9999	-0.79	4	4
alphaV beta3 Integrin	-0.021	0.11	-9999	-0.6	37	37
PTK2	-0.066	0.19	-9999	-0.57	122	122
positive regulation of JNK cascade	-0.038	0.11	-9999	-0.34	122	122
CDC42/GDP	-0.001	0.16	-9999	-0.46	122	122
Rac1/GDP	0.001	0.16	-9999	-0.45	122	122
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.047	0.13	-9999	-0.42	122	122
nectin-3/I-afadin	-0.069	0.2	-9999	-0.62	122	122
RAPGEF1	-0.01	0.18	-9999	-0.52	122	122
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.024	0.21	-9999	-0.61	122	122
PDGFB-D/PDGFRB	-0.003	0.047	-9999	-0.79	4	4
TLN1	0	0.1	-9999	-0.54	15	15
Rap1/GTP	-0.041	0.11	-9999	-0.36	122	122
IQGAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.003	0.035	-9999	-0.48	6	6
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.069	0.2	-9999	-0.62	122	122
PVR	0	0.009	-9999	-0.29	1	1
Necl-5(dimer)	0	0.009	-9999	-0.29	1	1
mol:GDP	-0.013	0.2	-9999	-0.58	122	122
MLLT4	-0.005	0.059	-9999	-0.72	7	7
PIK3CA	0	0.009	-9999	-0.29	1	1
PI3K	-0.058	0.17	-9999	-0.5	128	128
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.003	0.045	-9999	-0.6	6	6
positive regulation of lamellipodium assembly	-0.04	0.11	-9999	-0.35	122	122
PVRL1	0	0	-9999	-10000	0	0
PVRL3	-0.087	0.25	-9999	-0.79	121	121
PVRL2	-0.001	0.015	-9999	-0.29	3	3
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
CDH1	-0.02	0.12	-9999	-0.79	28	28
CLDN1	-0.036	0.15	-9999	-0.58	68	68
JAM-A/CLDN1	-0.074	0.18	-9999	-0.51	154	154
SRC	-0.078	0.22	-9999	-0.69	122	122
ITGB3	-0.028	0.14	-9999	-0.79	37	37
nectin-1(dimer)/I-afadin/I-afadin	-0.003	0.045	-9999	-0.6	6	6
FARP2	-0.018	0.2	-9999	-0.57	122	122
RAC1	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.06	0.17	-9999	-0.54	122	122
nectin-1/I-afadin	-0.003	0.045	-9999	-0.6	6	6
nectin-2/I-afadin	-0.004	0.046	-9999	-0.6	6	6
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	-0.06	0.17	-9999	-0.54	122	122
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.038	0.11	-9999	-0.34	122	122
alphaV/beta3 Integrin/Talin	-0.04	0.13	-9999	-0.61	42	42
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.004	0.046	-9999	-0.6	6	6
nectin-2(dimer)/I-afadin/I-afadin	-0.004	0.046	-9999	-0.6	6	6
PIP5K1C	-0.033	0.1	-9999	-0.29	126	126
VAV2	-0.02	0.2	-9999	-0.58	122	122
RAP1/GDP	-0.048	0.13	-9999	-0.42	122	122
ITGAV	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.06	0.17	-9999	-0.54	122	122
nectin-3(dimer)/I-afadin/I-afadin	-0.069	0.2	-9999	-0.62	122	122
Rac1/GTP	-0.049	0.14	-9999	-0.44	122	122
PTPRM	-0.037	0.12	-9999	-0.32	126	126
E-cadherin/beta catenin/alpha catenin	-0.013	0.074	-9999	-0.43	33	33
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.007	0.054	-9999	-0.45	15	15
RGS9BP	-0.019	0.072	-9999	-0.29	70	70
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.003	0.029	-9999	-0.29	11	11
mol:Na +	-0.02	0.053	-9999	-10000	0	0
mol:ADP	0.007	0.028	-9999	-10000	0	0
GNAT2	-0.001	0.018	-9999	-0.29	4	4
RGS9-1/Gbeta5/R9AP	-0.061	0.16	-9999	-0.53	106	106
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.015	-9999	-10000	0	0
GRK7	-0.002	0.026	-9999	-0.29	9	9
CNGB3	-0.01	0.054	-9999	-0.29	39	39
Cone Metarhodopsin II/X-Arrestin	-0.001	0.017	-9999	-10000	0	0
mol:Ca2+	-0.092	0.088	-9999	-0.28	39	39
Cone PDE6	-0.053	0.14	-9999	-0.46	106	106
Cone Metarhodopsin II	-0.003	0.019	-9999	-10000	0	0
Na + (4 Units)	-0.097	0.082	-9999	-10000	0	0
GNAT2/GDP	-0.052	0.14	-9999	-0.45	106	106
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	0.011	0.016	-9999	-10000	0	0
Cone Transducin	-0.008	0.057	-9999	-0.48	15	15
SLC24A2	-0.17	0.14	-9999	-0.29	649	649
GNB3/GNGT2	-0.009	0.071	-9999	-0.6	15	15
GNB3	-0.011	0.088	-9999	-0.63	19	19
GNAT2/GTP	-0.001	0.012	-9999	-10000	0	0
CNGA3	-0.028	0.086	-9999	-0.29	103	103
ARR3	-0.002	0.025	-9999	-0.29	8	8
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.02	0.053	-9999	-10000	0	0
mol:Pi	-0.061	0.16	-9999	-0.52	106	106
Cone CNG Channel	-0.016	0.04	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.17	0.14	-9999	-0.29	649	649
RGS9	-0.08	0.23	-9999	-0.73	121	121
PDE6C	0	0.009	-9999	-10000	0	0
GNGT2	-0.001	0.034	-9999	-0.79	2	2
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.002	0.022	-9999	-0.29	6	6

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	-0.001	0.034	-9999	-0.79	2	2
LAT2	-0.063	0.14	-9999	-0.53	51	51
AP1	-0.15	0.21	-9999	-0.57	154	154
mol:PIP3	-0.027	0.2	-9999	-0.5	99	99
IKBKB	0.002	0.12	-9999	-0.32	54	54
AKT1	-0.082	0.17	-9999	-0.68	44	44
IKBKG	0.002	0.12	-9999	-0.32	54	54
MS4A2	-0.069	0.22	-9999	-0.79	94	94
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.3	1	1
MAP3K1	0.005	0.13	-9999	-0.45	43	43
mol:Ca2+	-0.013	0.15	-9999	-0.36	99	99
LYN	0.011	0.004	-9999	-10000	0	0
CBLB	-0.062	0.14	-9999	-0.57	42	42
SHC1	0	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.062	0.16	-9999	-0.48	142	142
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0	0	-9999	-10000	0	0
PLD2	-0.096	0.2	-9999	-0.48	217	217
PTPN13	-0.031	0.17	-9999	-0.6	49	49
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	-0.41	45	45
SYK	0.011	0.01	-9999	-0.29	1	1
GRB2	0	0.009	-9999	-0.29	1	1
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.086	0.18	-9999	-0.51	99	99
LAT	-0.064	0.14	-9999	-0.58	43	43
PAK2	-0.004	0.14	-9999	-0.51	42	42
NFATC2	-0.1	0.24	-9999	-0.69	130	130
HRAS	-0.014	0.15	-9999	-0.55	45	45
GAB2	-0.004	0.042	-9999	-0.39	10	10
PLA2G1B	0.028	0.018	-9999	-10000	0	0
Fc epsilon R1	-0.12	0.25	-9999	-0.6	217	217
Antigen/IgE/Fc epsilon R1	-0.11	0.23	-9999	-0.55	217	217
mol:GDP	-0.02	0.16	-9999	-0.56	45	45
JUN	-0.005	0.063	-9999	-0.79	7	7
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
FOS	-0.24	0.36	-9999	-0.79	329	329
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.067	0.15	-9999	-0.46	95	95
CHUK	0.002	0.12	-9999	-0.32	54	54
KLRG1	-0.062	0.14	-9999	-0.55	43	43
VAV1	-0.064	0.14	-9999	-0.58	45	45
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.062	0.14	-9999	-0.57	42	42
negative regulation of mast cell degranulation	-0.056	0.12	-9999	-0.51	43	43
BTK	-0.061	0.14	-9999	-0.57	42	42
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.086	0.2	-9999	-0.47	166	166
GAB2/PI3K/SHP2	-0.091	0.19	-9999	-0.74	47	47
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.069	0.16	-9999	-0.68	42	42
RAF1	0.015	0.022	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.1	0.22	-9999	-0.54	173	173
FCER1G	0.003	0.012	-9999	-10000	0	0
FCER1A	-0.11	0.29	-9999	-0.8	161	161
Antigen/IgE/Fc epsilon R1/Fyn	-0.1	0.22	-9999	-0.51	217	217
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	0.009	0.081	-9999	-0.68	10	10
DUSP1	-0.1	0.26	-9999	-0.79	142	142
NF-kappa-B/RelA	-0.027	0.054	-9999	-0.23	6	6
actin cytoskeleton reorganization	-0.027	0.15	-9999	-0.56	41	41
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.059	0.14	-9999	-0.55	46	46
FER	-0.066	0.15	-9999	-0.58	50	50
RELA	0	0	-9999	-10000	0	0
ITK	-0.035	0.11	-9999	-0.6	39	39
SOS1	0	0	-9999	-10000	0	0
PLCG1	-0.017	0.16	-9999	-0.58	44	44
cytokine secretion	-0.019	0.04	-9999	-10000	0	0
SPHK1	-0.065	0.14	-9999	-0.58	46	46
PTK2	-0.029	0.16	-9999	-0.59	41	41
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.089	0.19	-9999	-0.54	99	99
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.022	0.2	-9999	-0.58	56	56
MAP2K2	0.023	0.019	-9999	-10000	0	0
MAP2K1	0.023	0.019	-9999	-10000	0	0
MAP2K7	0	0	-9999	-10000	0	0
KLRG1/SHP2	-0.057	0.13	-9999	-0.51	43	43
MAP2K4	0.017	0.033	-9999	-1	1	1
Fc epsilon R1/FcgammaRIIB	-0.11	0.23	-9999	-0.55	219	219
mol:Choline	-0.094	0.2	-9999	-0.47	217	217
SHC/Grb2/SOS1	-0.056	0.13	-9999	-0.54	41	41
FYN	-0.001	0.034	-9999	-0.79	2	2
DOK1	-0.001	0.018	-9999	-0.29	4	4
PXN	-0.019	0.15	-9999	-0.54	40	40
HCLS1	-0.062	0.14	-9999	-0.57	42	42
PRKCB	-0.015	0.16	-9999	-0.38	105	105
FCGR2B	-0.004	0.054	-9999	-0.7	6	6
IGHE	0	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.057	0.13	-9999	-0.52	43	43
LCP2	0	0.009	-9999	-0.29	1	1
PLA2G4A	-0.11	0.21	-9999	-0.55	166	166
RASA1	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.094	0.2	-9999	-0.47	217	217
IKK complex	0.019	0.093	-9999	-0.23	51	51
WIPF1	0	0	-9999	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.54	0.36	-9999	-0.79	751	751
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	-0.007	0.045	-9999	-0.29	27	27
TCEB1	-0.001	0.015	-9999	-0.29	3	3
HIF1A/p53	-0.001	0.005	-9999	-10000	0	0
HIF1A	-0.002	0.008	-9999	-10000	0	0
COPS5	0	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.003	0.018	-9999	-10000	0	0
FIH (dimer)	0	0	-9999	-10000	0	0
CDKN2A	-0.05	0.11	-9999	-0.29	188	188
ARNT/IPAS	-0.41	0.28	-9999	-0.6	751	751
HIF1AN	0	0	-9999	-10000	0	0
GNB2L1	0	0	-9999	-10000	0	0
HIF1A/ARNT	-0.001	0.005	-9999	-10000	0	0
CUL2	0	0	-9999	-10000	0	0
OS9	-0.001	0.013	-9999	-0.29	2	2
RACK1/Elongin B/Elongin C	-0.004	0.024	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.001	0.006	-9999	-10000	0	0
PHD1-3/OS9	-0.011	0.039	-9999	-0.47	2	2
HIF1A/RACK1/Elongin B/Elongin C	-0.003	0.016	-9999	-10000	0	0
VHL	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-0.29	1	1
HIF1A/JAB1	-0.001	0.005	-9999	-10000	0	0
EGLN3	-0.023	0.081	-9999	-0.3	83	83
EGLN2	-0.002	0.022	-9999	-0.29	6	6
EGLN1	-0.001	0.024	-9999	-0.79	1	1
TP53	0	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	-0.001	0.005	-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	-0.019	0.04	-9999	-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	0.2	-10000	0	-0.47	262	262
MAPK9	0.008	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.001	0.022	-10000	0	-0.2	13	13
GNB1/GNG2	-0.007	0.061	-10000	0	-0.52	15	15
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	0.008	0	-10000	0	-10000	0	0
Gs family/GTP	-0.12	0.21	-10000	0	-0.49	258	258
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	0.048	0.11	258	-10000	0	258
GNAL	-0.19	0.33	-10000	0	-0.79	258	258
GNG2	-0.011	0.092	-10000	0	-0.79	15	15
CRH	-0.003	0.032	-10000	0	-0.29	13	13
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.005	0.041	-10000	0	-0.44	9	9
MAPK11	0.007	0.024	-10000	0	-0.44	3	3

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	-0.005	0.056	-10000	0	-0.67	5	5
HDAC1	0.002	0.008	-10000	0	-10000	0	0
AES	0.001	0.004	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
DTX1	-0.07	0.22	-10000	0	-0.79	97	97
LRP6/FZD1	0	0.006	-10000	0	-10000	0	0
TLE1	-0.005	0.067	-10000	0	-0.79	8	8
AP1	-0.11	0.17	-10000	0	-0.36	332	332
NCSTN	0	0	-10000	0	-10000	0	0
ADAM10	-0.003	0.048	-10000	0	-0.79	4	4
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.008	0.044	-10000	0	-0.34	1	1
NICD/RBPSUH	-0.003	0.042	-10000	0	-0.7	4	4
WIF1	-0.41	0.39	-10000	0	-0.78	581	581
NOTCH1	-0.003	0.045	-10000	0	-0.74	4	4
PSENEN	-0.001	0.013	-10000	0	-10000	0	0
KREMEN2	-0.14	0.15	-10000	0	-0.29	527	527
DKK1	-0.08	0.19	-10000	0	-0.42	206	206
beta catenin/beta TrCP1	-0.002	0.029	-10000	0	-10000	0	0
APH1B	-0.001	0.024	-10000	0	-0.79	1	1
APH1A	0	0	-10000	0	-10000	0	0
AXIN1	0.003	0.015	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.003	0.039	-10000	0	-0.33	8	8
PSEN1	0	0	-10000	0	-10000	0	0
FOS	-0.24	0.36	-10000	0	-0.79	329	329
JUN	-0.005	0.063	-10000	0	-0.79	7	7
MAP3K7	0.001	0.01	-10000	0	-0.3	1	1
CTNNB1	-0.002	0.034	0.23	2	-10000	0	2
MAPK3	0	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.085	0.12	-10000	0	-0.61	33	33
HNF1A	-0.001	0.025	-10000	0	-0.29	8	8
CTBP1	0.001	0.004	-10000	0	-10000	0	0
MYC	-0.032	0.22	-10000	0	-1.5	24	24
NKD1	-0.009	0.069	-10000	0	-0.42	24	24
FZD1	0	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.041	0.13	-10000	0	-0.44	101	101
apoptosis	-0.11	0.17	-10000	0	-0.36	332	332
Delta 1/NOTCHprecursor	-0.005	0.055	-10000	0	-0.53	11	11
DLL1	-0.005	0.063	-10000	0	-0.79	7	7
PPARD	-0.001	0.013	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.014	-10000	0	-0.44	1	1
APC	0.003	0.015	-10000	0	-10000	0	0
DVL1	-0.037	0.035	-10000	0	-10000	0	0
CSNK2A1	0.011	0.003	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.12	0.14	-10000	0	-0.57	55	55
LRP6	0	0.009	-10000	0	-0.29	1	1
CSNK1A1	0.011	0.003	-10000	0	-10000	0	0
NLK	0.002	0.01	-10000	0	-10000	0	0
CCND1	-0.012	0.094	-10000	0	-1.5	4	4
WNT1	-0.001	0.013	-10000	0	-0.29	2	2
Axin1/APC/beta catenin	0.011	0.037	-10000	0	-10000	0	0
DKK2	-0.024	0.14	-10000	0	-0.76	35	35
NOTCH1 precursor/DVL1	-0.018	0.041	-10000	0	-0.64	4	4
GSK3B	0.001	0.003	-10000	0	-10000	0	0
FRAT1	0.001	0.004	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.041	0.13	-10000	0	-0.67	5	5
PPP2R5D	-0.015	0.037	0.35	6	-10000	0	6
MAPK1	0	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.24	0.23	-10000	0	-0.47	566	566
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.014	0.004	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0	0	-10000	0	-10000	0	0
HDAC4	-0.001	0.024	-10000	0	-0.79	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.011	0.076	0.6	1	-10000	0	1
CDKN1A	-0.002	0.04	-10000	0	-0.94	2	2
KAT2B	-0.001	0.024	-10000	0	-0.79	1	1
BAX	-0.001	0.018	-10000	0	-0.29	4	4
FOXO3	-0.001	0.017	-10000	0	-0.33	3	3
FOXO1	-0.009	0.082	-10000	0	-0.79	12	12
FOXO4	0.022	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	-0.56	0.35	-10000	0	-0.77	788	788
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.01	0.029	-10000	0	-0.6	1	1
PPARGC1A	-0.17	0.32	-10000	0	-0.76	241	241
FHL2	-0.004	0.054	-10000	0	-0.7	6	6
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.007	-10000	0	-10000	0	0
HIST2H4A	-0.011	0.076	-10000	0	-0.6	1	1
SIRT1/FOXO3a	0	0.014	-10000	0	-0.25	3	3
SIRT1	0	0.009	0.21	2	-10000	0	2
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0.017	-10000	0	-0.52	1	1
SIRT1/Histone H1b	-0.003	0.012	-10000	0	-10000	0	0
apoptosis	0	0.011	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.11	0.21	-10000	0	-0.52	230	230
p53/SIRT1	0.001	0.019	0.43	2	-10000	0	2
SIRT1/FOXO4	0	0.007	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.007	0.059	-10000	0	-0.48	17	17
HIST1H1E	0.015	0.022	-10000	0	-10000	0	0
SIRT1/p300	0	0.007	-10000	0	-10000	0	0
muscle cell differentiation	0.002	0.023	0.51	1	-10000	0	1
TP53	0	0.009	0.21	2	-10000	0	2
KU70/SIRT1/BAX	0	0.011	-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	-0.42	0.27	-10000	0	-0.6	760	760
ACSS2	0.02	0.019	-10000	0	-0.6	1	1
SIRT1/PCAF/MYOD	-0.002	0.023	-10000	0	-0.52	1	1

×

FAS signaling pathway (CD95)

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.011	0.052	0.28	37	-10000	0	37
RFC1	0.011	0.052	0.28	38	-10000	0	38
PRKDC	0.01	0.053	0.28	37	-10000	0	37
RIPK1	0	0.001	-10000	0	-10000	0	0
CASP7	-0.023	0.037	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.017	0.067	0.25	17	-0.38	18	35
MAP2K4	-0.058	0.16	-10000	0	-0.5	22	22
mol:ceramide	-0.032	0.12	-10000	0	-0.55	22	22
GSN	0.004	0.076	0.28	37	-0.49	14	51
FASLG/FAS/FADD/FAF1/Caspase 8	-0.031	0.074	0.23	14	-0.46	18	32
FAS	0.003	0.06	-10000	0	-0.8	6	6
BID	0.001	0.015	0.32	2	-10000	0	2
MAP3K1	-0.021	0.094	-10000	0	-0.3	11	11
MAP3K7	0.006	0.011	-10000	0	-0.29	1	1
RB1	0.01	0.052	0.28	36	-0.29	1	37
CFLAR	-0.001	0.023	-10000	0	-0.76	1	1
HGF/MET	-0.14	0.26	-10000	0	-0.58	256	256
ARHGDIB	0.01	0.053	0.28	39	-10000	0	39
FADD	0.003	0.037	-10000	0	-0.31	15	15
actin filament polymerization	-0.004	0.076	0.49	14	-0.28	37	51
NFKB1	-0.076	0.1	-10000	0	-0.33	1	1
MAPK8	-0.12	0.24	-10000	0	-0.43	403	403
DFFA	0.011	0.052	0.28	37	-10000	0	37
DNA fragmentation during apoptosis	0.01	0.052	0.28	37	-10000	0	37
FAS/FADD/MET	-0.096	0.21	-10000	0	-0.55	190	190
CFLAR/RIP1	-0.001	0.017	-10000	0	-0.56	1	1
FAIM3	-0.002	0.056	-10000	0	-0.33	27	27
FAF1	0.008	0.006	-10000	0	-10000	0	0
PARP1	0.01	0.052	0.28	39	-10000	0	39
DFFB	0.011	0.052	0.28	37	-10000	0	37
CHUK	-0.066	0.088	-10000	0	-10000	0	0
FASLG	-0.015	0.11	-10000	0	-0.42	58	58
FAS/FADD	-0.006	0.053	-10000	0	-0.64	6	6
HGF	-0.053	0.2	-10000	0	-0.79	73	73
LMNA	0.01	0.047	0.26	37	-10000	0	37
CASP6	0.01	0.052	0.28	39	-10000	0	39
CASP10	0.005	0.049	-10000	0	-0.8	4	4
CASP3	0.013	0.063	0.34	39	-10000	0	39
PTPN13	-0.023	0.13	-10000	0	-0.79	32	32
CASP8	0.003	0.023	0.45	2	-10000	0	2
IL6	-0.47	0.67	-10000	0	-1.4	400	400
MET	-0.14	0.3	-10000	0	-0.78	189	189
ICAD/CAD	0.01	0.048	0.26	37	-10000	0	37
FASLG/FAS/FADD/FAF1/Caspase 10	-0.033	0.12	-10000	0	-0.56	22	22
activation of caspase activity by cytochrome c	0.001	0.015	0.32	2	-10000	0	2
PAK2	0.01	0.052	0.28	37	-10000	0	37
BCL2	-0.022	0.14	-10000	0	-0.79	37	37

×

Stabilization and expansion of the E-cadherin adherens junction

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.009	0.052	-10000	0	-0.32	29	29
epithelial cell differentiation	-0.011	0.069	-10000	0	-0.44	28	28
CYFIP2	-0.01	0.065	-10000	0	-0.36	31	31
ENAH	0.058	0.057	-10000	0	-10000	0	0
EGFR	-0.29	0.38	-10000	0	-0.78	410	410
EPHA2	-0.004	0.058	-10000	0	-0.79	6	6
MYO6	-0.011	0.067	-10000	0	-0.42	29	29
CTNNB1	0	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.005	0.038	-10000	0	-0.52	4	4
AQP5	-0.23	0.29	-10000	0	-0.58	428	428
CTNND1	0	0.009	-10000	0	-0.29	1	1
mol:PI-4-5-P2	-0.011	0.065	-10000	0	-0.41	28	28
regulation of calcium-dependent cell-cell adhesion	-0.032	0.11	-10000	0	-0.41	85	85
EGF	-0.15	0.31	-10000	0	-0.78	214	214
NCKAP1	0	0	-10000	0	-10000	0	0
AQP3	-0.037	0.14	-10000	0	-0.52	80	80
cortical microtubule organization	-0.011	0.069	-10000	0	-0.44	28	28
GO:0000145	0.027	0.068	-10000	0	-0.39	28	28
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.011	0.07	-10000	0	-0.44	28	28
MLLT4	-0.005	0.059	-10000	0	-0.72	7	7
ARF6/GDP	-0.011	0.059	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.036	-10000	0	-0.47	6	6
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.037	0.071	-10000	0	-0.38	28	28
PVRL2	-0.001	0.015	-10000	0	-0.29	3	3
ZYX	-0.011	0.066	-10000	0	-0.42	28	28
ARF6/GTP	-0.003	0.033	-10000	0	-0.43	6	6
CDH1	-0.02	0.12	-10000	0	-0.79	28	28
EGFR/EGFR/EGF/EGF	-0.24	0.26	-10000	0	-0.46	562	562
RhoA/GDP	-0.011	0.065	-10000	0	-0.41	28	28
actin cytoskeleton organization	0.033	0.07	-10000	0	-0.39	29	29
IGF-1R heterotetramer	-0.02	0.12	-10000	0	-0.59	36	36
GIT1	-0.001	0.02	-10000	0	-0.29	5	5
IGF1R	-0.02	0.12	-10000	0	-0.6	36	36
IGF1	-0.18	0.33	-10000	0	-0.79	247	247
DIAPH1	-0.002	0.043	-10000	0	-0.69	4	4
Wnt receptor signaling pathway	0.011	0.069	0.44	28	-10000	0	28
RHOA	0	0	-10000	0	-10000	0	0
RhoA/GTP	-0.011	0.06	-10000	0	-10000	0	0
CTNNA1	0	0	-10000	0	-10000	0	0
VCL	0.033	0.072	-10000	0	-0.4	29	29
EFNA1	0	0.009	-10000	0	-0.29	1	1
LPP	0.031	0.078	-10000	0	-0.39	36	36
Ephrin A1/EPHA2	-0.012	0.069	-10000	0	-0.4	34	34
SEC6/SEC8	-0.012	0.065	-10000	0	-0.74	1	1
MGAT3	-0.033	0.11	-10000	0	-0.42	85	85
HGF/MET	-0.11	0.2	-10000	0	-0.44	262	262
HGF	-0.053	0.2	-10000	0	-0.79	73	73
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.009	0.052	-10000	0	-0.32	29	29
actin cable formation	0.072	0.055	-10000	0	-0.32	1	1
KIAA1543	0.032	0.087	-10000	0	-0.46	29	29
KIFC3	-0.011	0.068	-10000	0	-0.42	30	30
NCK1	0	0	-10000	0	-10000	0	0
EXOC3	0	0	-10000	0	-10000	0	0
ACTN1	-0.011	0.067	-10000	0	-0.42	29	29
NCK1/GIT1	-0.001	0.013	-10000	0	-10000	0	0
mol:GDP	-0.011	0.069	-10000	0	-0.44	28	28
EXOC4	0	0	-10000	0	-10000	0	0
STX4	-0.011	0.066	-10000	0	-0.42	28	28
PIP5K1C	-0.011	0.066	-10000	0	-0.42	28	28
LIMA1	-0.001	0.024	-10000	0	-0.79	1	1
ABI1	0	0	-10000	0	-10000	0	0
ROCK1	-0.01	0.053	-10000	0	-10000	0	0
adherens junction assembly	0.048	0.083	-10000	0	-0.62	7	7
IGF-1R heterotetramer/IGF1	-0.11	0.19	-10000	0	-0.43	279	279
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.004	0.046	-10000	0	-0.6	6	6
MET	-0.14	0.3	-10000	0	-0.78	189	189
PLEKHA7	-0.012	0.076	-10000	0	-0.46	28	28
mol:GTP	-0.003	0.035	-10000	0	-0.46	6	6
establishment of epithelial cell apical/basal polarity	-0.011	0.061	-10000	0	-0.7	1	1
cortical actin cytoskeleton stabilization	-0.009	0.052	-10000	0	-0.32	29	29
regulation of cell-cell adhesion	0.033	0.07	-10000	0	-0.39	29	29
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.009	0.052	-10000	0	-0.32	29	29

×

IL27-mediated signaling events

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
TGFB1	0.001	0.017	-10000	0	-0.29	3	3
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.035	0.13	0.41	52	-10000	0	52
IL27/IL27R/JAK1	-0.074	0.19	-10000	0	-0.6	73	73
TBX21	-0.043	0.21	-10000	0	-0.58	91	91
IL12B	-0.055	0.12	-10000	0	-0.29	229	229
IL12A	-0.027	0.14	-10000	0	-0.61	58	58
IL6ST	-0.091	0.27	-10000	0	-0.8	137	137
IL27RA/JAK1	-0.008	0.073	-10000	0	-1.1	4	4
IL27	-0.025	0.095	-10000	0	-0.29	121	121
TYK2	0.01	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.12	0.18	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.035	0.13	0.41	52	-10000	0	52
T cell proliferation during immune response	0.035	0.13	0.41	52	-10000	0	52
MAPKKK cascade	-0.035	0.13	-10000	0	-0.41	52	52
STAT3	0	0	-10000	0	-10000	0	0
STAT2	0	0	-10000	0	-10000	0	0
STAT1	-0.004	0.039	-10000	0	-0.3	19	19
IL12RB1	-0.004	0.067	-10000	0	-0.32	43	43
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.059	0.23	-10000	0	-0.61	103	103
IL27/IL27R/JAK2/TYK2	-0.035	0.13	-10000	0	-0.41	52	52
positive regulation of T cell mediated cytotoxicity	-0.035	0.13	-10000	0	-0.41	52	52
STAT1 (dimer)	-0.092	0.22	0.46	22	-0.71	65	87
JAK2	0.005	0.025	-10000	0	-0.79	1	1
JAK1	0	0.024	-10000	0	-0.79	1	1
STAT2 (dimer)	-0.044	0.11	-10000	0	-0.44	27	27
T cell proliferation	-0.18	0.25	-10000	0	-0.46	421	421
IL12/IL12R/TYK2/JAK2	0.012	0.069	-10000	0	-10000	0	0
IL17A	-0.12	0.18	-10000	0	-10000	0	0
mast cell activation	0.035	0.13	0.41	52	-10000	0	52
IFNG	-0.001	0.025	-10000	0	-0.074	18	18
T cell differentiation	-0.004	0.006	-10000	0	-0.019	33	33
STAT3 (dimer)	-0.044	0.11	-10000	0	-0.44	26	26
STAT5A (dimer)	-0.048	0.12	-10000	0	-0.46	33	33
STAT4 (dimer)	-0.062	0.15	-10000	0	-0.49	67	67
STAT4	-0.032	0.16	-10000	0	-0.78	45	45
T cell activation	-0.009	0.009	0.13	3	-10000	0	3
IL27R/JAK2/TYK2	-0.062	0.17	-10000	0	-0.55	52	52
GATA3	-0.039	0.28	-10000	0	-1.4	40	40
IL18	0.006	0.032	-10000	0	-10000	0	0
positive regulation of mast cell cytokine production	-0.044	0.11	-10000	0	-0.43	27	27
IL27/EBI3	-0.026	0.083	-10000	0	-0.52	14	14
IL27RA	-0.001	0.078	-10000	0	-1.4	3	3
IL6	-0.29	0.38	-10000	0	-0.79	401	401
STAT5A	-0.006	0.067	-10000	0	-0.79	8	8
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.004	0.03	0.48	3	-10000	0	3
IL1B	0.002	0.073	-10000	0	-0.52	19	19
EBI3	-0.004	0.076	-10000	0	-0.49	21	21
TNF	-0.001	0.074	-10000	0	-0.61	13	13

×

LPA4-mediated signaling events

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
ADCY4	0	0.1	-9999	-0.53	41	41
ADCY5	-0.16	0.26	-9999	-0.53	354	354
ADCY6	0.02	0	-9999	-10000	0	0
ADCY7	0.02	0	-9999	-10000	0	0
ADCY1	-0.008	0.097	-9999	-0.53	29	29
ADCY2	-0.032	0.15	-9999	-0.53	90	90
ADCY3	0.02	0.005	-9999	-10000	0	0
ADCY8	0.01	0.028	-9999	-10000	0	0
PRKCE	0.011	0	-9999	-10000	0	0
ADCY9	0.02	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.032	0.1	-9999	-0.31	75	75

×

Effects of Botulinum toxin

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.003	0.041	-9999	-0.2	43	43
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.046	0.13	-9999	-0.6	46	46
STXBP1	-0.006	0.067	-9999	-0.79	8	8
ACh/CHRNA1	-0.062	0.082	-9999	-0.25	16	16
RAB3GAP2/RIMS1/UNC13B	-0.038	0.11	-9999	-0.52	46	46
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	-0.066	0.18	-9999	-0.43	170	170
mol:ACh	0.001	0.031	-9999	-0.11	62	62
RAB3GAP2	0	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.038	0.093	-9999	-0.39	54	54
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.062	0.082	-9999	-0.25	16	16
UNC13B	0	0	-9999	-10000	0	0
CHRNA1	-0.099	0.14	-9999	-0.29	371	371
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.059	0.12	-9999	-0.47	60	60
SNAP25	-0.009	0.068	-9999	-0.37	35	35
VAMP2	0	0	-9999	-10000	0	0
SYT1	-0.087	0.18	-9999	-0.38	253	253
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.01	0.053	-9999	-0.52	8	8
STX1A/SNAP25 fragment 1/VAMP2	-0.038	0.093	-9999	-0.39	54	54

×

Canonical Wnt signaling pathway

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
HDAC1	0.004	0.018	-10000	0	-10000	0	0
AES	0.004	0.015	-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	0.006	-10000	0	-10000	0	0
SMAD4	-0.001	0.024	-10000	0	-0.79	1	1
DKK2	-0.024	0.14	-10000	0	-0.76	35	35
TLE1	-0.002	0.069	-10000	0	-0.79	8	8
MACF1	0.006	0.006	-10000	0	-10000	0	0
CTNNB1	0.1	0.087	-10000	0	-10000	0	0
WIF1	-0.41	0.39	-10000	0	-0.77	581	581
beta catenin/RanBP3	0.014	0.078	0.37	46	-10000	0	46
KREMEN2	-0.14	0.15	-10000	0	-0.29	527	527
DKK1	-0.08	0.19	-10000	0	-0.42	206	206
beta catenin/beta TrCP1	0.1	0.083	-10000	0	-10000	0	0
FZD1	0	0.002	-10000	0	-10000	0	0
AXIN2	-0.014	0.21	-10000	0	-1.5	20	20
AXIN1	0.007	0.006	-10000	0	-10000	0	0
RAN	0.001	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.007	0.024	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.092	0.078	0.3	1	-0.49	6	7
Axin1/APC/GSK3	0.001	0.014	0.24	1	-10000	0	1
Axin1/APC/GSK3/beta catenin/Macf1	0.077	0.033	-10000	0	-10000	0	0
HNF1A	0.002	0.029	-10000	0	-0.29	7	7
CTBP1	0.004	0.016	-10000	0	-10000	0	0
MYC	-0.018	0.23	-10000	0	-1.5	25	25
RANBP3	0.001	0.003	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.085	0.12	-10000	0	-0.6	33	33
NKD1	-0.009	0.069	-10000	0	-0.42	24	24
TCF4	-0.005	0.083	-10000	0	-0.78	12	12
TCF3	0.004	0.017	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0	0.006	-10000	0	-10000	0	0
Ran/GTP	0	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.014	0.099	0.45	45	-0.42	1	46
LEF1	-0.036	0.1	-10000	0	-0.3	140	140
DVL1	0.071	0.065	-10000	0	-10000	0	0
CSNK2A1	0	0.002	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.098	0.089	-10000	0	-0.54	6	6
DKK1/LRP6/Kremen 2	-0.12	0.14	-10000	0	-0.57	55	55
LRP6	0.002	0.01	-10000	0	-0.29	1	1
CSNK1A1	0.004	0.018	-10000	0	-10000	0	0
NLK	0.011	0.014	-10000	0	-0.3	2	2
CCND1	0.002	0.11	-10000	0	-1.6	4	4
WNT1	0.005	0.014	-10000	0	-0.29	2	2
GSK3A	0.009	0.006	-10000	0	-10000	0	0
GSK3B	0	0.001	-10000	0	-10000	0	0
FRAT1	0	0	-10000	0	-10000	0	0
PPP2R5D	0.044	0.045	0.34	7	-10000	0	7
APC	0.001	0.009	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.14	0.13	0.27	566	-10000	0	566
CREBBP	0.004	0.016	-10000	0	-10000	0	0

×

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	-0.035	0.12	-10000	0	-0.59	40	40
FYN	0.017	0.18	-10000	0	-0.7	47	47
LAT/GRAP2/SLP76	-0.028	0.14	-10000	0	-0.65	42	42
IKBKB	-0.001	0.013	-10000	0	-0.29	2	2
AKT1	0.031	0.12	-10000	0	-0.46	44	44
B2M	0.012	0.004	-10000	0	-10000	0	0
IKBKG	-0.008	0.026	-10000	0	-0.14	14	14
MAP3K8	-0.007	0.072	-10000	0	-0.74	10	10
mol:Ca2+	-0.024	0.047	-10000	0	-0.12	212	212
integrin-mediated signaling pathway	-0.002	0.028	-10000	0	-0.52	3	3
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.022	0.17	-10000	0	-0.7	45	45
TRPV6	-0.16	0.32	-10000	0	-0.77	225	225
CD28	0.002	0.074	-10000	0	-0.52	18	18
SHC1	0.012	0.18	-10000	0	-0.75	44	44
receptor internalization	-0.001	0.2	-10000	0	-0.76	53	53
PRF1	0	0.22	-10000	0	-1.2	30	30
KRAS	-0.001	0.013	-10000	0	-0.29	2	2
GRB2	0	0.009	-10000	0	-0.29	1	1
COT/AKT1	0.032	0.1	-10000	0	-0.37	47	47
LAT	0.01	0.18	-10000	0	-0.73	48	48
EntrezGene:6955	0.001	0.003	-10000	0	-10000	0	0
CD3D	-0.023	0.14	-10000	0	-0.48	78	78
CD3E	-0.016	0.13	-10000	0	-0.49	61	61
CD3G	-0.031	0.16	-10000	0	-0.56	82	82
RASGRP2	0.004	0.041	-10000	0	-0.18	45	45
RASGRP1	0.036	0.12	-10000	0	-0.47	44	44
HLA-A	0.009	0.031	-10000	0	-0.29	11	11
RASSF5	-0.002	0.042	-10000	0	-0.66	4	4
RAP1A/GTP/RAPL	-0.002	0.028	-10000	0	-0.52	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.033	0.043	-10000	0	-0.12	39	39
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.014	0.047	-10000	0	-0.23	33	33
PRKCA	-0.013	0.084	-10000	0	-0.3	62	62
GRAP2	-0.013	0.1	-10000	0	-0.72	21	21
mol:IP3	0.019	0.15	0.27	182	-0.45	41	223
EntrezGene:6957	0.001	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.005	0.2	-10000	0	-0.9	40	40
ORAI1	0.077	0.15	0.38	211	-10000	0	211
CSK	0.009	0.18	-10000	0	-0.74	46	46
B7 family/CD28	-0.026	0.18	-10000	0	-0.7	51	51
CHUK	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.001	0.21	-10000	0	-0.75	61	61
PTPN6	0.008	0.18	-10000	0	-0.76	45	45
VAV1	0.011	0.18	-10000	0	-0.75	46	46
Monovalent TCR/CD3	-0.023	0.2	-10000	0	-0.65	72	72
CBL	0	0	-10000	0	-10000	0	0
LCK	0.011	0.19	-10000	0	-0.77	46	46
PAG1	0.009	0.18	-10000	0	-0.75	46	46
RAP1A	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.001	0.21	-10000	0	-0.76	58	58
CD80	-0.068	0.13	-10000	0	-0.29	285	285
CD86	0.008	0.023	-10000	0	-0.3	6	6
PDK1/CARD11/BCL10/MALT1	-0.017	0.057	-10000	0	-0.28	35	35
HRAS	-0.003	0.028	-10000	0	-0.29	10	10
GO:0035030	0	0.15	-10000	0	-0.57	51	51
CD8A	0	0.073	-10000	0	-0.8	5	5
CD8B	-0.021	0.15	-10000	0	-0.55	66	66
PTPRC	-0.001	0.071	-10000	0	-0.48	19	19
PDK1/PKC theta	0.034	0.15	-10000	0	-0.6	45	45
CSK/PAG1	0.014	0.18	-10000	0	-0.75	42	42
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.002	0.018	-10000	0	-10000	0	0
GRAP2/SLP76	-0.034	0.17	-10000	0	-0.75	45	45
STIM1	0.04	0.078	-10000	0	-10000	0	0
RAS family/GTP	0.041	0.054	-10000	0	-0.17	32	32
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.005	0.22	-10000	0	-0.84	53	53
mol:DAG	-0.007	0.1	-10000	0	-0.41	42	42
RAP1A/GDP	0.016	0.018	-10000	0	-10000	0	0
PLCG1	0.001	0.003	-10000	0	-10000	0	0
CD247	-0.008	0.12	-10000	0	-0.58	37	37
cytotoxic T cell degranulation	0.003	0.21	-10000	0	-1	33	33
RAP1A/GTP	-0.003	0.013	-10000	0	-0.071	5	5
mol:PI-3-4-5-P3	0.027	0.14	-10000	0	-0.56	45	45
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.012	0.17	0.29	170	-0.6	42	212
NRAS	-0.001	0.013	-10000	0	-0.29	2	2
ZAP70	-0.031	0.12	-10000	0	-0.42	81	81
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.025	0.14	-10000	0	-0.62	42	42
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.031	0.13	-10000	0	-0.56	53	53
CARD11	-0.007	0.052	-10000	0	-0.34	23	23
PRKCB	-0.012	0.084	-10000	0	-0.32	53	53
PRKCE	-0.006	0.068	-10000	0	-0.29	36	36
PRKCQ	0.025	0.17	-10000	0	-0.69	47	47
LCP2	0	0.009	-10000	0	-0.29	1	1
BCL10	0	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.032	0.1	-10000	0	-0.39	44	44
IKK complex	0.041	0.044	-10000	0	-0.12	30	30
RAS family/GDP	-0.002	0.006	-10000	0	-10000	0	0
MAP3K14	0.036	0.08	-10000	0	-0.29	39	39
PDPK1	0.034	0.11	-10000	0	-0.44	41	41
TCR/CD3/MHC I/CD8/Fyn	-0.004	0.23	-10000	0	-0.92	50	50

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.002	0.032	-10000	0	-0.79	1	1
SVIL	-0.004	0.056	-10000	0	-0.79	5	5
ZNF318	0.022	0.057	-10000	0	-10000	0	0
JMJD2C	-0.003	0.041	-10000	0	-0.12	106	106
T-DHT/AR/Ubc9	-0.081	0.18	-10000	0	-0.54	147	147
CARM1	0	0	-10000	0	-10000	0	0
PRDX1	0.003	0.012	-10000	0	-0.29	1	1
PELP1	0.005	0.012	-10000	0	-10000	0	0
CTNNB1	0.001	0.015	-10000	0	-10000	0	0
AKT1	0.007	0.018	-10000	0	-10000	0	0
PTK2B	0.001	0.013	-10000	0	-10000	0	0
MED1	0.002	0.047	-10000	0	-0.29	20	20
MAK	0.011	0.1	0.26	1	-0.55	20	21
response to oxidative stress	0.001	0.004	-10000	0	-10000	0	0
HIP1	-0.005	0.061	-10000	0	-0.79	6	6
GSN	-0.012	0.091	-10000	0	-0.79	14	14
NCOA2	-0.039	0.17	-10000	0	-0.79	54	54
NCOA6	-0.001	0.02	-10000	0	-0.29	1	1
DNA-PK	0.022	0.058	0.22	2	-10000	0	2
NCOA4	0	0	-10000	0	-10000	0	0
PIAS3	0.001	0.015	-10000	0	-10000	0	0
cell proliferation	-0.008	0.11	-10000	0	-0.87	11	11
XRCC5	0.006	0.015	-10000	0	-10000	0	0
UBE3A	-0.005	0.03	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.094	0.21	-10000	0	-0.57	162	162
FHL2	-0.018	0.12	-10000	0	-1.2	5	5
RANBP9	0	0.018	-10000	0	-10000	0	0
JMJD1A	-0.011	0.056	-10000	0	-0.14	152	152
CDK6	-0.009	0.093	-10000	0	-0.73	17	17
TGFB1I1	-0.003	0.046	-10000	0	-0.79	3	3
T-DHT/AR/CyclinD1	-0.094	0.19	-10000	0	-0.52	163	163
XRCC6	0.006	0.015	-10000	0	-10000	0	0
T-DHT/AR	-0.067	0.21	-10000	0	-0.53	164	164
CTDSP1	0.004	0.005	-10000	0	-10000	0	0
CTDSP2	0.015	0.038	-10000	0	-10000	0	0
BRCA1	-0.002	0.034	-10000	0	-0.49	3	3
TCF4	0.003	0.088	-10000	0	-0.78	12	12
CDKN2A	-0.042	0.11	-10000	0	-0.29	167	167
SRF	0.024	0.019	-10000	0	-10000	0	0
NKX3-1	-0.082	0.19	-10000	0	-0.83	41	41
KLK3	-0.17	0.5	-10000	0	-1.5	127	127
TMF1	0.004	0.005	-10000	0	-10000	0	0
HNRNPA1	0.008	0.021	-10000	0	-10000	0	0
AOF2	-0.008	0.023	-10000	0	-0.072	127	127
APPL1	0.034	0.032	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.074	0.19	-10000	0	-0.54	146	146
AR	-0.1	0.27	-10000	0	-0.79	147	147
UBA3	0.004	0.005	-10000	0	-10000	0	0
PATZ1	0.008	0.021	-10000	0	-10000	0	0
PAWR	0.003	0.025	-10000	0	-0.79	1	1
PRKDC	0.005	0.024	-10000	0	-0.29	4	4
PA2G4	0.011	0.027	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.069	0.17	-10000	0	-0.5	146	146
RPS6KA3	-0.008	0.074	-10000	0	-0.79	9	9
T-DHT/AR/ARA70	-0.085	0.18	-10000	0	-0.54	147	147
LATS2	0.009	0.023	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.064	0.18	0.19	1	-0.49	147	148
Cyclin D3/CDK11 p58	0	0.006	-10000	0	-10000	0	0
VAV3	-0.01	0.075	-10000	0	-0.43	26	26
KLK2	-0.12	0.32	-10000	0	-1.2	79	79
CASP8	0.004	0.011	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.099	0.2	-10000	0	-0.54	181	181
TMPRSS2	-0.17	0.39	-10000	0	-1.2	137	137
CCND1	-0.016	0.074	-10000	0	-0.34	46	46
PIAS1	-0.005	0.03	-10000	0	-10000	0	0
mol:T-DHT	-0.008	0.033	-10000	0	-0.078	182	182
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.011	0.049	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.085	0.2	-10000	0	-0.54	161	161
CMTM2	0.003	0.013	-10000	0	-10000	0	0
SNURF	-0.021	0.13	-10000	0	-0.79	29	29
ZMIZ1	0.004	0.03	-10000	0	-0.36	1	1
CCND3	0.002	0.01	-10000	0	-0.29	1	1
TGIF1	0.008	0.021	-10000	0	-10000	0	0
FKBP4	-0.003	0.033	-10000	0	-0.3	9	9

×

Regulation of Androgen receptor activity

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
HDAC1	0.021	0.003	-9999	-10000	0	0
SMARCC1	0.005	0.019	-9999	-10000	0	0
REL	-0.006	0.09	-9999	-0.79	14	14
HDAC7	0.008	0.13	-9999	-0.58	19	19
JUN	0	0.063	-9999	-0.79	7	7
EP300	0	0	-9999	-10000	0	0
KAT2B	-0.001	0.024	-9999	-0.79	1	1
KAT5	0.002	0.005	-9999	-10000	0	0
MAPK14	0.006	0.095	-9999	-0.61	25	25
FOXO1	-0.009	0.082	-9999	-0.79	12	12
T-DHT/AR	-0.004	0.14	-9999	-0.52	35	35
MAP2K6	-0.01	0.12	-9999	-0.78	26	26
BRM/BAF57	-0.001	0.01	-9999	-10000	0	0
MAP2K4	0.008	0.025	-9999	-0.79	1	1
SMARCA2	0.004	0.006	-9999	-10000	0	0
PDE9A	-0.088	0.29	-9999	-1.2	64	64
NCOA2	-0.032	0.17	-9999	-0.79	54	54
CEBPA	-0.005	0.075	-9999	-0.79	10	10
EHMT2	0.005	0.006	-9999	-10000	0	0
cell proliferation	0.014	0.15	-9999	-0.49	26	26
NR0B1	-0.01	0.053	-9999	-0.29	37	37
EGR1	-0.25	0.37	-9999	-0.79	347	347
RXRs/9cRA	-0.12	0.21	-9999	-0.48	268	268
AR/RACK1/Src	-0.005	0.11	-9999	-0.5	28	28
AR/GR	-0.054	0.13	-9999	-0.45	58	58
GNB2L1	0.002	0.004	-9999	-10000	0	0
PKN1	0	0.009	-9999	-0.29	1	1
RCHY1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.001	0.003	-9999	-10000	0	0
MAPK8	0.015	0.061	-9999	-0.61	10	10
T-DHT/AR/TIF2/CARM1	-0.018	0.16	-9999	-0.51	78	78
SRC	0.021	0.094	-9999	-0.46	34	34
NR3C1	-0.012	0.095	-9999	-0.79	16	16
KLK3	-0.2	0.41	-9999	-1.1	164	164
APPBP2	0.008	0.017	-9999	-0.29	3	3
TRIM24	0.005	0.006	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.028	0.099	-9999	-0.51	34	34
TMPRSS2	-0.16	0.41	-9999	-1.2	138	138
RXRG	-0.19	0.34	-9999	-0.79	268	268
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	0.008	0.006	-9999	-10000	0	0
NR2C2	-0.008	0.079	-9999	-0.79	11	11
KLK2	-0.043	0.24	-9999	-0.73	103	103
AR	-0.028	0.14	-9999	-0.34	172	172
SENP1	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-0.29	1	1
MDM2	0.004	0.024	-9999	-0.29	5	5
SRY	0.003	0.01	-9999	-10000	0	0
GATA2	-0.024	0.13	-9999	-0.63	41	41
MYST2	0.002	0.01	-9999	-0.29	1	1
HOXB13	-0.14	0.15	-9999	-0.3	501	501
T-DHT/AR/RACK1/Src	-0.013	0.1	-9999	-0.51	28	28
positive regulation of transcription	-0.024	0.13	-9999	-0.63	41	41
DNAJA1	0.009	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.013	-9999	-10000	0	0
NCOA1	0.012	0.026	-9999	-0.82	1	1
SPDEF	-0.057	0.2	-9999	-0.61	110	110
T-DHT/AR/TIF2	0.011	0.1	-9999	-0.45	27	27
T-DHT/AR/Hsp90	-0.035	0.095	-9999	-0.51	34	34
GSK3B	0.008	0.006	-9999	-10000	0	0
NR2C1	0.003	0.006	-9999	-10000	0	0
mol:T-DHT	0.014	0.099	-9999	-0.5	34	34
SIRT1	0	0	-9999	-10000	0	0
ZMIZ2	0.005	0.013	-9999	-10000	0	0
POU2F1	0.021	0.026	-9999	-0.42	1	1
T-DHT/AR/DAX-1	-0.036	0.099	-9999	-0.52	34	34
CREBBP	0	0	-9999	-10000	0	0
SMARCE1	0.004	0.017	-9999	-0.3	3	3

×

IL12-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.004	0.13	-10000	0	-0.4	54	54
TBX21	-0.013	0.34	-10000	0	-1.3	57	57
B2M	0.011	0.005	-10000	0	-10000	0	0
TYK2	0.017	0.015	-10000	0	-10000	0	0
IL12RB1	0.004	0.072	-10000	0	-0.33	43	43
GADD45B	0.031	0.22	-10000	0	-0.81	34	34
IL12RB2	-0.056	0.19	-10000	0	-0.49	133	133
GADD45G	0.021	0.22	-10000	0	-0.81	36	36
natural killer cell activation	0.007	0.018	-10000	0	-10000	0	0
RELB	-0.003	0.028	-10000	0	-0.29	10	10
RELA	0	0	-10000	0	-10000	0	0
IL18	0.007	0.048	-10000	0	-0.29	18	18
IL2RA	-0.031	0.12	-10000	0	-0.38	87	87
IFNG	-0.04	0.1	-10000	0	-0.29	150	150
STAT3 (dimer)	0.024	0.22	-10000	0	-0.66	55	55
HLA-DRB5	-0.017	0.096	-10000	0	-0.33	84	84
FASLG	0.002	0.29	-10000	0	-1.1	49	49
NF kappa B2 p52/RelB	-0.079	0.2	-10000	0	-0.8	54	54
CD4	0.008	0.006	-10000	0	-10000	0	0
SOCS1	-0.005	0.043	-10000	0	-0.32	18	18
EntrezGene:6955	-0.006	0.014	-10000	0	-10000	0	0
CD3D	-0.026	0.14	-10000	0	-0.49	78	78
CD3E	-0.019	0.13	-10000	0	-0.5	61	61
CD3G	-0.035	0.17	-10000	0	-0.57	82	82
IL12Rbeta2/JAK2	-0.026	0.15	-10000	0	-0.61	50	50
CCL3	0.012	0.26	-10000	0	-0.97	41	41
CCL4	0.014	0.25	-10000	0	-0.95	38	38
HLA-A	0.008	0.032	-10000	0	-0.3	11	11
IL18/IL18R	0.02	0.14	-10000	0	-0.54	55	55
NOS2	0.018	0.25	-10000	0	-0.9	44	44
IL12/IL12R/TYK2/JAK2/SPHK2	-0.003	0.13	-10000	0	-0.4	53	53
IL1R1	-0.001	0.31	-10000	0	-1.2	49	49
IL4	-0.004	0.018	-10000	0	-10000	0	0
JAK2	0.016	0.029	-10000	0	-0.82	1	1
EntrezGene:6957	-0.005	0.013	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.032	0.25	-10000	0	-0.99	50	50
RAB7A	0.045	0.19	-10000	0	-0.74	25	25
lysosomal transport	0.047	0.19	-10000	0	-0.7	25	25
FOS	-0.35	0.66	-10000	0	-1.3	342	342
STAT4 (dimer)	0.02	0.26	-10000	0	-0.86	56	56
STAT5A (dimer)	-0.086	0.22	-10000	0	-0.76	66	66
GZMA	0.002	0.28	-10000	0	-1.1	40	40
GZMB	-0.012	0.31	-10000	0	-1.1	52	52
HLX	-0.001	0.015	-10000	0	-0.29	3	3
LCK	0.003	0.29	-10000	0	-0.86	67	67
TCR/CD3/MHC II/CD4	-0.065	0.19	-10000	0	-0.52	94	94
IL2/IL2R	-0.03	0.1	-10000	0	-0.48	41	41
MAPK14	0.035	0.22	-10000	0	-0.77	43	43
CCR5	0.025	0.22	-10000	0	-0.87	32	32
IL1B	0.005	0.098	-10000	0	-0.69	19	19
STAT6	0.025	0.087	-10000	0	-0.24	14	14
STAT4	-0.032	0.16	-10000	0	-0.78	45	45
STAT3	0	0	-10000	0	-10000	0	0
STAT1	-0.005	0.038	-10000	0	-0.29	19	19
NFKB1	0	0	-10000	0	-10000	0	0
NFKB2	0	0.009	-10000	0	-0.29	1	1
IL12B	-0.047	0.12	-10000	0	-0.3	131	131
CD8A	0	0.074	-10000	0	-0.79	5	5
CD8B	-0.022	0.14	-10000	0	-0.54	66	66
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.003	0.13	0.4	54	-10000	0	54
IL2RB	-0.012	0.064	-10000	0	-0.32	42	42
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.24	-10000	0	-0.78	56	56
IL2RG	-0.017	0.085	-10000	0	-0.36	53	53
IL12	-0.052	0.16	-10000	0	-0.59	65	65
STAT5A	-0.006	0.067	-10000	0	-0.79	8	8
CD247	-0.011	0.12	-10000	0	-0.58	37	37
IL2	-0.002	0.025	-10000	0	-0.29	8	8
SPHK2	0	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.031	0.19	-10000	0	-0.73	67	67
IL12/IL12R/TYK2/JAK2	0.007	0.29	-10000	0	-0.83	72	72
MAP2K3	0.03	0.22	-10000	0	-0.79	41	41
RIPK2	-0.001	0.02	-10000	0	-0.29	5	5
MAP2K6	0.026	0.23	-10000	0	-0.77	47	47
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.008	0.026	-10000	0	-0.79	1	1
IL18RAP	-0.014	0.15	-10000	0	-0.73	42	42
IL12Rbeta1/TYK2	0.014	0.056	-10000	0	-0.63	2	2
EOMES	-0.024	0.18	-10000	0	-1.5	17	17
STAT1 (dimer)	0.027	0.22	-10000	0	-0.7	44	44
T cell proliferation	0.031	0.2	-10000	0	-0.62	56	56
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0	0.11	-10000	0	-0.79	20	20
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.062	0.17	-10000	0	-0.74	46	46
ATF2	0.041	0.21	-10000	0	-0.74	40	40

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.13	0.22	-9999	-0.46	301	301
TC10/GTP	-0.11	0.18	-9999	-0.4	285	285
Insulin Receptor/Insulin/IRS1/Shp2	-0.02	0.097	-9999	-0.49	45	45
HRAS	-0.003	0.028	-9999	-0.29	10	10
APS homodimer	-0.013	0.06	-9999	-0.29	49	49
GRB14	-0.1	0.22	-9999	-0.48	231	231
FOXO3	-0.015	0.07	-9999	-0.7	10	10
AKT1	-0.058	0.12	-9999	-0.51	11	11
INSR	0.012	0.009	-9999	-0.29	1	1
Insulin Receptor/Insulin	-0.003	0.026	-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	-0.79	285	285
CRK	0	0	-9999	-10000	0	0
PTPN1	0.033	0.03	-9999	-10000	0	0
CAV1	-0.099	0.24	-9999	-0.5	259	259
CBL/APS/CAP/Crk-II/C3G	-0.12	0.2	-9999	-0.45	285	285
Insulin Receptor/Insulin/IRS1/NCK2	-0.02	0.097	-9999	-0.49	45	45
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.023	0.096	-9999	-0.42	59	59
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.012	0.055	-9999	-10000	0	0
RPS6KB1	-0.009	0.13	-9999	-0.46	11	11
PARD6A	-0.002	0.023	-9999	-0.29	7	7
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	-0.01	0.089	-9999	-0.79	14	14
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.05	0.11	-9999	-0.48	11	11
HRAS/GTP	-0.016	0.073	-9999	-0.47	2	2
Insulin Receptor	0.012	0.009	-9999	-0.29	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.019	0.09	-9999	-0.45	45	45
PRKCI	-0.013	0.032	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.063	0.14	-9999	-0.4	143	143
SHC1	0	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0.002	-9999	-10000	0	0
PI3K	-0.023	0.097	-9999	-0.43	59	59
NCK2	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
mol:H2O2	0	0.003	-9999	-10000	0	0
HRAS/GDP	-0.002	0.019	-9999	-10000	0	0
AKT2	-0.058	0.12	-9999	-0.51	11	11
PRKCZ	-0.014	0.036	-9999	-0.6	1	1
SH2B2	-0.013	0.061	-9999	-0.29	49	49
SHC/SHIP	-0.017	0.085	-9999	-0.42	45	45
F2RL2	-0.06	0.15	-9999	-0.36	185	185
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	-0.13	0.21	-9999	-0.48	285	285
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0.003	-9999	-10000	0	0
INPP5D	0.007	0.096	-9999	-0.46	45	45
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.01	0.08	-9999	-1	7	7
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.032	0.16	-9999	-0.79	45	45
p62DOK/RasGAP	0	0.003	-9999	-10000	0	0
INS	0.003	0.004	-9999	-10000	0	0
mol:PI-3-4-P2	0.007	0.095	-9999	-0.45	45	45
GRB2	0	0.009	-9999	-0.29	1	1
EIF4EBP1	-0.014	0.14	-9999	-0.46	26	26
PTPRA	0.012	0.002	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.013	0.064	-9999	-0.32	45	45
Insulin Receptor/Insulin/IRS1	-0.021	0.098	-9999	-0.5	45	45
Insulin Receptor/Insulin/IRS3	-0.001	0.007	-9999	-10000	0	0
Par3/Par6	-0.027	0.075	-9999	-0.45	24	24

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.055	0.12	-9999	-0.57	6	6
RAD9A	0	0.009	-9999	-0.29	1	1
AP1	-0.18	0.28	-9999	-0.61	330	330
IFNAR2	0.01	0.025	-9999	-0.79	1	1
AKT1	-0.036	0.11	-9999	-0.28	165	165
ER alpha/Oestrogen	-0.11	0.22	-9999	-0.61	166	166
NFX1/SIN3/HDAC complex	0.026	0.025	-9999	-10000	0	0
EGF	-0.15	0.31	-9999	-0.78	214	214
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	-0.067	0.089	-9999	-0.58	4	4
SAP18	0.006	0.006	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.14	0.15	-9999	-0.29	561	561
WRN	0	0	-9999	-10000	0	0
SP1	0.011	0.006	-9999	-10000	0	0
SP3	0.009	0.005	-9999	-10000	0	0
TERF2IP	0	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.052	0.078	-9999	-0.55	3	3
Mad/Max	0	0.006	-9999	-10000	0	0
TERT	-0.056	0.12	-9999	-0.61	5	5
CCND1	-0.048	0.13	-9999	-1.3	4	4
MAX	0.009	0.005	-9999	-10000	0	0
RBBP7	0.004	0.026	-9999	-0.29	8	8
RBBP4	0.005	0.025	-9999	-0.79	1	1
TERF2	0	0	-9999	-10000	0	0
PTGES3	0	0	-9999	-10000	0	0
SIN3A	0.006	0.006	-9999	-10000	0	0
Telomerase/911	0.012	0.024	-9999	-10000	0	0
CDKN1B	0.009	0.074	-9999	-0.86	3	3
RAD1	0	0	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
SAP30	0.005	0.019	-9999	-0.29	4	4
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.009	0.005	-9999	-10000	0	0
JUN	0.002	0.064	-9999	-0.79	7	7
E6	0	0.001	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0	-9999	-10000	0	0
FOS	-0.23	0.37	-9999	-0.79	329	329
IFN-gamma/IRF1	-0.025	0.063	-9999	-0.36	5	5
PARP2	0	0	-9999	-10000	0	0
BLM	-0.03	0.089	-9999	-0.29	113	113
Telomerase	-0.006	0.028	-9999	-10000	0	0
IRF1	0.011	0.02	-9999	-0.28	3	3
ESR1	-0.15	0.29	-9999	-0.58	288	288
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0.007	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0	0.007	-9999	-10000	0	0
HDAC1	0.006	0.006	-9999	-10000	0	0
HDAC2	0.011	0.005	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.021	0.011	-9999	-10000	0	0
ABL1	0	0	-9999	-10000	0	0
MXD1	0.009	0.01	-9999	-0.29	1	1
MRE11A	0	0	-9999	-10000	0	0
HUS1	0	0	-9999	-10000	0	0
RPS6KB1	-0.001	0.015	-9999	-0.29	3	3
TERT/NF kappa B1/14-3-3	-0.065	0.1	-9999	-0.67	3	3
NR2F2	0.001	0.042	-9999	-0.79	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	0.001	0.016	-9999	-0.29	3	3
NFKB1	0	0	-9999	-10000	0	0
HNRNPC	0	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0	0	-9999	-10000	0	0
EGFR	-0.29	0.38	-9999	-0.78	410	410
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.33	0.35	-9999	-0.66	552	552
MYC	-0.008	0.12	-9999	-0.79	24	24
IL2	0.004	0.026	-9999	-0.29	8	8
KU	0	0	-9999	-10000	0	0
RAD50	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-0.29	1	1
TGFB1	0.001	0.016	-9999	-0.29	3	3
TRF2/BLM	-0.017	0.051	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.063	0.087	-9999	-0.58	4	4
SP1/HDAC2	0	0	-9999	-10000	0	0
PINX1	0	0	-9999	-10000	0	0
Telomerase/EST1A	-0.052	0.078	-9999	-0.55	3	3
Smad3/Myc	-0.012	0.076	-9999	-0.52	24	24
911 complex	0	0.004	-9999	-10000	0	0
IFNG	-0.03	0.1	-9999	-0.28	150	150
Telomerase/PinX1	-0.052	0.078	-9999	-0.55	3	3
Telomerase/AKT1/mTOR/p70S6K	0.003	0.055	-9999	-10000	0	0
SIN3B	0.006	0.006	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
Telomerase/EST1B	-0.052	0.078	-9999	-0.52	4	4
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	-0.052	0.078	-9999	-0.55	3	3
E2F1	-0.085	0.14	-9999	-0.29	345	345
ZNFX1	0.006	0.006	-9999	-10000	0	0
PIF1	-0.061	0.12	-9999	-0.29	227	227
NCL	0	0	-9999	-10000	0	0
DKC1	-0.001	0.013	-9999	-0.29	2	2
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.002	0.036	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.024	0.037	-9999	-0.63	1	1
positive regulation of JNK cascade	-0.05	0.1	-9999	-0.51	2	2
Syndecan-4/ADAM12	-0.032	0.055	-9999	-0.63	1	1
CCL5	-0.014	0.079	-9999	-0.36	44	44
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0	0	-9999	-10000	0	0
ITGA5	0	0.009	-9999	-0.29	1	1
SDCBP	0	0	-9999	-10000	0	0
PLG	-0.001	0.026	-9999	-0.29	8	8
ADAM12	-0.019	0.077	-9999	-0.31	68	68
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	-0.001	0.02	-9999	-0.29	5	5
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.054	0.044	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.07	0.13	-9999	-0.59	5	5
Syndecan-4/CXCL12/CXCR4	-0.053	0.11	-9999	-0.6	1	1
Syndecan-4/Laminin alpha3	-0.13	0.19	-9999	-0.5	120	120
MDK	-0.012	0.057	-9999	-0.29	43	43
Syndecan-4/FZD7	-0.033	0.068	-9999	-0.56	2	2
Syndecan-4/Midkine	-0.028	0.042	-9999	-0.63	1	1
FZD7	-0.017	0.11	-9999	-0.79	23	23
Syndecan-4/FGFR1/FGF	-0.19	0.2	-9999	-0.67	15	15
THBS1	-0.004	0.053	-9999	-0.79	5	5
integrin-mediated signaling pathway	-0.034	0.072	-9999	-0.7	2	2
positive regulation of MAPKKK cascade	-0.05	0.1	-9999	-0.51	2	2
Syndecan-4/TACI	-0.036	0.066	-9999	-0.52	5	5
CXCR4	-0.007	0.045	-9999	-0.29	26	26
cell adhesion	-0.02	0.061	-9999	-0.34	29	29
Syndecan-4/Dynamin	-0.024	0.036	-9999	-0.63	1	1
Syndecan-4/TSP1	-0.026	0.046	-9999	-0.63	1	1
Syndecan-4/GIPC	-0.024	0.036	-9999	-0.63	1	1
Syndecan-4/RANTES	-0.03	0.052	-9999	-0.57	2	2
ITGB1	0	0	-9999	-10000	0	0
LAMA1	-0.088	0.25	-9999	-0.77	124	124
LAMA3	-0.2	0.34	-9999	-0.79	276	276
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.004	0.13	-9999	-0.72	31	31
Syndecan-4/alpha-Actinin	-0.024	0.038	-9999	-0.63	1	1
TFPI	-0.041	0.18	-9999	-0.79	57	57
F2	0	0.034	-9999	-0.29	14	14
alpha5/beta1 Integrin	0	0.006	-9999	-10000	0	0
positive regulation of cell adhesion	-0.16	0.23	-9999	-0.58	113	113
ACTN1	-0.001	0.024	-9999	-0.79	1	1
TNC	-0.022	0.12	-9999	-0.64	37	37
Syndecan-4/CXCL12	-0.056	0.11	-9999	-0.5	7	7
FGF6	-0.001	0.034	-9999	-0.79	2	2
RHOA	0	0	-9999	-10000	0	0
CXCL12	-0.061	0.21	-9999	-0.79	85	85
TNFRSF13B	-0.028	0.11	-9999	-0.39	78	78
FGF2	-0.32	0.39	-9999	-0.79	446	446
FGFR1	-0.009	0.08	-9999	-0.68	14	14
Syndecan-4/PI-4-5-P2	-0.018	0.048	-9999	-0.64	1	1
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.11	0.15	-9999	-0.3	431	431
cell migration	-0.024	0.019	-9999	-10000	0	0
PRKCD	0.005	0.014	-9999	-0.29	1	1
vasculogenesis	-0.025	0.044	-9999	-0.6	1	1
SDC4	-0.018	0.051	-9999	-0.68	1	1
Syndecan-4/Tenascin C	-0.035	0.075	-9999	-0.74	2	2
Syndecan-4/PI-4-5-P2/PKC alpha	-0.043	0.035	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.024	0.036	-9999	-0.63	1	1
MMP9	-0.12	0.15	-9999	-0.29	483	483
Rac1/GTP	-0.028	0.057	-9999	-0.34	29	29
cytoskeleton organization	-0.024	0.036	-9999	-0.6	1	1
GIPC1	0	0.009	-9999	-0.29	1	1
Syndecan-4/TFPI	-0.046	0.098	-9999	-0.52	8	8

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.002	0.01	-10000	0	-10000	0	0
HSPA8	0.001	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.099	0.2	0.25	1	-0.56	165	166
AKT1	0.014	0.006	-10000	0	-10000	0	0
GSC	-0.036	0.3	-10000	0	-1.5	42	42
NKX2-5	-0.045	0.1	-10000	0	-0.29	171	171
muscle cell differentiation	0.007	0.051	0.76	1	-10000	0	1
SMAD2-3/SMAD4/SP1	0.006	0.04	-10000	0	-0.45	2	2
SMAD4	0.014	0.041	-10000	0	-0.82	1	1
CBFB	0	0	-10000	0	-10000	0	0
SAP18	0.001	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.19	0.25	-10000	0	-0.51	406	406
SMAD3/SMAD4/VDR	0.005	0.03	-10000	0	-0.43	2	2
MYC	-0.017	0.12	-10000	0	-0.79	24	24
CDKN2B	0.029	0.13	-10000	0	-1.5	7	7
AP1	-0.12	0.2	-10000	0	-0.41	329	329
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.002	0.02	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.001	0.041	-10000	0	-0.32	4	4
SP3	0	0	-10000	0	-10000	0	0
CREB1	0	0	-10000	0	-10000	0	0
FOXH1	-0.044	0.12	-10000	0	-0.29	204	204
SMAD3/SMAD4/GR	-0.01	0.073	-10000	0	-0.56	17	17
GATA3	-0.037	0.15	-10000	0	-0.57	70	70
SKI/SIN3/HDAC complex/NCoR1	0.002	0.014	-10000	0	-10000	0	0
MEF2C/TIF2	-0.055	0.13	-10000	0	-0.54	57	57
endothelial cell migration	-0.008	0.06	1.5	1	-10000	0	1
MAX	0.001	0.005	-10000	0	-10000	0	0
RBBP7	-0.002	0.025	-10000	0	-0.29	8	8
RBBP4	0	0.024	-10000	0	-0.79	1	1
RUNX2	-0.005	0.036	-10000	0	-0.29	17	17
RUNX3	-0.006	0.066	-10000	0	-0.79	7	7
RUNX1	-0.001	0.024	-10000	0	-0.79	1	1
CTBP1	0	0	-10000	0	-10000	0	0
NR3C1	-0.011	0.095	-10000	0	-0.79	16	16
VDR	0	0	-10000	0	-10000	0	0
CDKN1A	0.05	0.078	-10000	0	-1.5	2	2
KAT2B	0	0.024	-10000	0	-0.79	1	1
SMAD2/SMAD2/SMAD4/FOXH1	-0.03	0.072	-10000	0	-0.46	6	6
DCP1A	0	0	-10000	0	-10000	0	0
SKI	0.001	0.002	-10000	0	-10000	0	0
SERPINE1	0.007	0.061	-10000	0	-1.5	1	1
SMAD3/SMAD4/ATF2	-0.003	0.04	-10000	0	-0.56	4	4
SMAD3/SMAD4/ATF3	-0.078	0.19	-10000	0	-0.55	154	154
SAP30	-0.001	0.018	-10000	0	-0.29	4	4
Cbp/p300/PIAS3	0.005	0.023	-10000	0	-10000	0	0
JUN	-0.074	0.22	-10000	0	-0.4	323	323
SMAD3/SMAD4/IRF7	-0.02	0.068	-10000	0	-0.36	18	18
TFE3	0.017	0.006	-10000	0	-10000	0	0
COL1A2	0.027	0.1	-10000	0	-1.2	3	3
mesenchymal cell differentiation	0.004	0.034	0.54	1	-10000	0	1
DLX1	-0.053	0.13	-10000	0	-0.32	184	184
TCF3	0	0.009	-10000	0	-10000	0	0
FOS	-0.22	0.37	-10000	0	-0.78	329	329
SMAD3/SMAD4/Max	-0.002	0.029	-10000	0	-0.54	1	1
Cbp/p300/SNIP1	0	0.002	-10000	0	-10000	0	0
ZBTB17	0	0.006	-10000	0	-10000	0	0
LAMC1	0.042	0.047	-10000	0	-0.62	2	2
TGIF2/HDAC complex/SMAD3/SMAD4	-0.001	0.028	-10000	0	-0.54	1	1
IRF7	-0.031	0.092	-10000	0	-0.31	104	104
ESR1	-0.15	0.28	-10000	0	-0.58	287	287
HNF4A	-0.006	0.041	-10000	0	-0.29	22	22
MEF2C	0	0.097	-10000	0	-0.62	5	5
SMAD2-3/SMAD4	-0.003	0.033	-10000	0	-0.53	1	1
Cbp/p300/Src-1	0.003	0.022	-10000	0	-0.52	1	1
IGHV3OR16-13	-0.001	0.01	-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	0.029	-10000	0	-0.29	11	11
HDAC1	0.001	0.002	-10000	0	-10000	0	0
HDAC2	0.001	0.002	-10000	0	-10000	0	0
SNIP1	0.001	0.003	-10000	0	-10000	0	0
GCN5L2	0.001	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.001	0.029	-10000	0	-0.53	1	1
MSG1/HSC70	-0.22	0.29	-10000	0	-0.6	406	406
SMAD2	0.015	0.02	-10000	0	-10000	0	0
SMAD3	0.015	0.029	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.034	0.038	-10000	0	-0.35	2	2
SMAD2/SMAD2/SMAD4	0.026	0.039	-10000	0	-1.1	1	1
NCOR1	0	0.024	-10000	0	-0.79	1	1
NCOA2	-0.039	0.17	-10000	0	-0.79	54	54
NCOA1	-0.001	0.024	-10000	0	-0.79	1	1
MYOD/E2A	-0.003	0.022	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.028	0.051	-10000	0	-0.41	2	2
IFNB1	0.011	0.093	-10000	0	-0.42	18	18
SMAD3/SMAD4/MEF2C	-0.027	0.078	-10000	0	-0.76	3	3
CITED1	-0.3	0.38	-10000	0	-0.77	421	421
SMAD2-3/SMAD4/ARC105	-0.001	0.028	-10000	0	-0.47	1	1
RBL1	-0.003	0.043	-10000	0	-0.59	5	5
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.047	0.062	-10000	0	-0.49	7	7
RUNX1-3/PEBPB2	-0.004	0.049	-10000	0	-0.58	7	7
SMAD7	-0.067	0.14	-10000	0	-0.58	8	8
MYC/MIZ-1	-0.012	0.09	-10000	0	-0.61	24	24
SMAD3/SMAD4	0.017	0.06	0.29	22	-0.43	2	24
IL10	0.018	0.12	-10000	0	-0.5	42	42
PIASy/HDAC complex	0.011	0.004	-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	0.014	0.11	-10000	0	-0.5	40	40
CDK4	0.001	0.02	-10000	0	-0.29	4	4
PIAS4	0.011	0.004	-10000	0	-10000	0	0
ATF3	-0.11	0.27	-10000	0	-0.78	154	154
SMAD3/SMAD4/SP1	0	0.032	-10000	0	-0.52	2	2
FOXG1	-0.023	0.077	-10000	0	-0.29	80	80
FOXO3	0.025	0.034	-10000	0	-0.6	3	3
FOXO1	0.02	0.066	-10000	0	-0.6	12	12
FOXO4	0.026	0.008	-10000	0	-10000	0	0
heart looping	0	0.096	-10000	0	-0.61	5	5
CEBPB	0.012	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.029	0.078	-10000	0	-0.55	10	10
MYOD1	-0.004	0.033	-10000	0	-0.29	14	14
SMAD3/SMAD4/HNF4	-0.006	0.037	-10000	0	-0.68	1	1
SMAD3/SMAD4/GATA3	-0.024	0.11	-10000	0	-0.56	40	40
SnoN/SIN3/HDAC complex/NCoR1	-0.003	0.029	-10000	0	-0.29	11	11
SMAD3/SMAD4/RUNX1-3/PEBPB2	0	0.051	-10000	0	-0.52	8	8
SMAD3/SMAD4/SP1-3	0.003	0.029	-10000	0	-0.45	2	2
MED15	0	0	-10000	0	-10000	0	0
SP1	0.019	0.015	-10000	0	-10000	0	0
SIN3B	0.001	0.002	-10000	0	-10000	0	0
SIN3A	0.001	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.014	0.091	-10000	0	-0.4	13	13
ITGB5	0.052	0.046	-10000	0	-0.41	1	1
TGIF/SIN3/HDAC complex/CtBP	0.002	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.074	0.19	-10000	0	-0.55	147	147
AR	-0.1	0.27	-10000	0	-0.78	147	147
negative regulation of cell growth	-0.025	0.072	-10000	0	-0.48	2	2
SMAD3/SMAD4/MYOD	-0.006	0.034	-10000	0	-0.54	1	1
E2F5	-0.005	0.039	-10000	0	-0.29	20	20
E2F4	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.002	0.057	-10000	0	-0.44	2	2
SMAD2-3/SMAD4/FOXO1-3a-4	0.002	0.046	-10000	0	-0.32	9	9
TFDP1	-0.001	0.018	-10000	0	-0.29	4	4
SMAD3/SMAD4/AP1	-0.12	0.2	-10000	0	-0.43	192	192
SMAD3/SMAD4/RUNX2	-0.004	0.034	-10000	0	-0.54	1	1
TGIF2	0	0	-10000	0	-10000	0	0
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	-0.002	0.041	-10000	0	-0.79	3	3

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.06	0.077	-9999	-0.42	7	7
EPHB2	-0.005	0.038	-9999	-0.29	19	19
Syndecan-2/TACI	-0.018	0.075	-9999	-0.52	19	19
LAMA1	-0.088	0.25	-9999	-0.77	124	124
Syndecan-2/alpha2 ITGB1	-0.12	0.21	-9999	-0.46	293	293
HRAS	-0.003	0.028	-9999	-0.29	10	10
Syndecan-2/CASK	-0.003	0.033	-9999	-0.52	4	4
ITGA5	0	0.009	-9999	-0.29	1	1
BAX	0.033	0.061	-9999	-0.72	3	3
EPB41	0	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.002	0.03	-9999	-0.47	4	4
LAMA3	-0.2	0.34	-9999	-0.79	276	276
EZR	-0.001	0.015	-9999	-0.29	3	3
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.1	0.27	-9999	-0.79	146	146
Syndecan-2/MMP2	-0.008	0.07	-9999	-0.63	12	12
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.016	0.096	-9999	-0.6	29	29
dendrite morphogenesis	-0.005	0.037	-9999	-0.51	4	4
Syndecan-2/GM-CSF	-0.006	0.039	-9999	-0.52	4	4
determination of left/right symmetry	0.017	0.039	-9999	-0.6	4	4
Syndecan-2/PKC delta	-0.003	0.033	-9999	-0.52	4	4
GNB2L1	0	0	-9999	-10000	0	0
MAPK3	0.022	0.039	-9999	-0.47	4	4
MAPK1	0.022	0.039	-9999	-0.47	4	4
Syndecan-2/RACK1	-0.003	0.032	-9999	-0.48	4	4
NF1	-0.001	0.024	-9999	-0.79	1	1
FGFR/FGF/Syndecan-2	0.017	0.039	-9999	-0.6	4	4
ITGA2	-0.021	0.13	-9999	-0.79	29	29
MAPK8	0.027	0.065	-9999	-0.57	12	12
Syndecan-2/alpha2/beta1 Integrin	-0.062	0.18	-9999	-0.5	133	133
Syndecan-2/Kininogen	-0.005	0.039	-9999	-0.52	4	4
ITGB1	0	0	-9999	-10000	0	0
SRC	-0.003	0.029	-9999	-0.45	4	4
Syndecan-2/CASK/Protein 4.1	-0.002	0.03	-9999	-0.48	4	4
extracellular matrix organization	-0.003	0.033	-9999	-0.51	4	4
actin cytoskeleton reorganization	-0.06	0.077	-9999	-0.42	7	7
Syndecan-2/Caveolin-2/Ras	-0.066	0.17	-9999	-0.48	146	146
Syndecan-2/Laminin alpha3	-0.13	0.23	-9999	-0.52	280	280
Syndecan-2/RasGAP	-0.003	0.03	-9999	-0.45	4	4
alpha5/beta1 Integrin	0	0.006	-9999	-10000	0	0
PRKCD	0	0.009	-9999	-0.29	1	1
Syndecan-2 dimer	-0.005	0.037	-9999	-0.52	4	4
GO:0007205	0	0.002	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.003	0.028	-9999	-0.43	4	4
RHOA	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
TNFRSF13B	-0.028	0.11	-9999	-0.39	78	78
RASA1	0	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.016	0.096	-9999	-0.6	29	29
Syndecan-2/Synbindin	-0.002	0.032	-9999	-0.52	4	4
TGFB1	-0.001	0.015	-9999	-0.29	3	3
CASP3	0.03	0.032	-9999	-0.46	4	4
FN1	-0.12	0.14	-9999	-0.29	431	431
Syndecan-2/IL8	-0.022	0.085	-9999	-0.52	26	26
SDC2	0.017	0.04	-9999	-0.6	4	4
KNG1	-0.006	0.041	-9999	-10000	0	0
Syndecan-2/Neurofibromin	-0.003	0.036	-9999	-0.52	5	5
TRAPPC4	0	0	-9999	-10000	0	0
CSF2	-0.007	0.045	-9999	-0.29	26	26
Syndecan-2/TGFB1	-0.003	0.033	-9999	-0.52	4	4
Syndecan-2/Syntenin/PI-4-5-P2	-0.002	0.03	-9999	-0.48	4	4
Syndecan-2/Ezrin	-0.002	0.03	-9999	-0.47	4	4
PRKACA	0.029	0.035	-9999	-0.47	5	5
angiogenesis	-0.021	0.085	-9999	-0.52	26	26
MMP2	-0.008	0.079	-9999	-0.75	12	12
IL8	-0.033	0.13	-9999	-0.42	87	87
calcineurin-NFAT signaling pathway	-0.018	0.075	-9999	-0.52	19	19

×

Regulation of p38-alpha and p38-beta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.018	0.12	-9999	-0.77	26	26
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	-0.001	0.024	-9999	-0.79	1	1
RAC1-CDC42/GTP/PAK family	-0.12	0.14	-9999	-0.27	487	487
response to UV	0	0	-9999	-10000	0	0
YES1	-0.001	0.024	-9999	-0.79	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	0.034	-9999	-0.79	2	2
MAP3K12	0	0	-9999	-10000	0	0
FGR	-0.001	0.025	-9999	-0.54	2	2
p38 alpha/TAB1	-0.007	0.033	-9999	-0.32	4	4
PRKG1	-0.053	0.2	-9999	-0.79	74	74
DUSP8	-0.002	0.042	-9999	-0.66	4	4
PGK/cGMP/p38 alpha	-0.032	0.1	-9999	-0.39	77	77
apoptosis	-0.006	0.032	-9999	-0.3	4	4
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0	0	-9999	-10000	0	0
DUSP1	-0.1	0.26	-9999	-0.79	142	142
PAK1	-0.007	0.044	-9999	-0.29	25	25
SRC	0	0.009	-9999	-0.29	1	1
RAC1/OSM/MEKK3/MKK3	0	0.006	-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	-0.001	0.013	-9999	-0.29	2	2
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.018	0.068	-9999	-0.34	21	21
BLK	-0.044	0.11	-9999	-0.3	159	159
HCK	-0.004	0.033	-9999	-10000	0	0
MAP2K3	0	0.009	-9999	-0.29	1	1
DUSP16	0	0	-9999	-10000	0	0
DUSP10	-0.001	0.015	-9999	-0.29	3	3
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.029	0.048	-9999	-0.34	4	4
positive regulation of innate immune response	0.024	0.074	-9999	-0.36	21	21
LCK	-0.02	0.1	-9999	-0.41	53	53
p38alpha-beta/MKP7	-0.012	0.054	-9999	-0.38	8	8
p38alpha-beta/MKP5	-0.012	0.054	-9999	-0.34	20	20
PGK/cGMP	-0.041	0.15	-9999	-0.61	74	74
PAK2	0	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.058	0.13	-9999	-0.37	158	158
CDC42	0	0	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
PAK3	-0.35	0.39	-9999	-0.79	487	487

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.003	0.063	-10000	0	-0.66	9	9
CDKN2C	0.006	0.037	-10000	0	-0.78	2	2
CDKN2A	-0.052	0.12	-10000	0	-0.31	188	188
CCND2	0.006	0.033	0.24	8	-0.16	12	20
RB1	-0.007	0.032	0.19	4	-0.25	8	12
CDK4	0.01	0.03	0.25	9	-10000	0	9
CDK6	0.006	0.039	0.27	8	-0.21	14	22
G1/S progression	-0.006	0.036	0.25	8	-0.18	4	12

×

Osteopontin-mediated events

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
IKK alpha homodimer	-0.037	0.084	-9999	-0.43	37	37
NF kappa B1 p50/RelA/I kappa B alpha	-0.023	0.069	-9999	-0.46	6	6
alphaV/beta3 Integrin/Osteopontin/Src	-0.046	0.076	-9999	-10000	0	0
AP1	-0.14	0.21	-9999	-0.79	38	38
ILK	-0.006	0.11	-9999	-0.46	37	37
bone resorption	-0.038	0.11	-9999	-0.67	22	22
PTK2B	0	0	-9999	-10000	0	0
PYK2/p130Cas	0.004	0.089	-9999	-0.48	10	10
ITGAV	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.018	0.1	-9999	-0.6	32	32
alphaV/beta3 Integrin/Osteopontin	-0.05	0.1	-9999	-0.52	37	37
MAP3K1	-0.007	0.11	-9999	-0.48	37	37
JUN	-0.005	0.063	-9999	-0.79	7	7
MAPK3	0.009	0.1	-9999	-0.43	37	37
MAPK1	0.009	0.1	-9999	-0.43	37	37
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0.002	0.13	-9999	-0.53	39	39
ITGB3	-0.027	0.14	-9999	-0.78	37	37
NFKBIA	0.022	0.1	-9999	-0.48	10	10
FOS	-0.24	0.36	-9999	-0.79	329	329
CD44	-0.001	0.015	-9999	-0.29	3	3
CHUK	0	0	-9999	-10000	0	0
PLAU	0.021	0.1	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.022	0.065	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.021	0.11	-9999	-0.59	37	37
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.008	0.11	-9999	-0.47	37	37
VAV3	-0.002	0.11	-9999	-0.44	44	44
MAP3K14	-0.004	0.11	-9999	-0.47	37	37
ROCK2	-0.023	0.13	-9999	-0.79	32	32
SPP1	-0.075	0.12	-9999	-0.28	288	288
RAC1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.036	0.083	-9999	-0.45	16	16
MMP2	-0.074	0.21	-9999	-0.68	38	38

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.008	0.043	-9999	-0.39	10	10
ELF1	-0.012	0.051	-9999	-0.38	16	16
CCNA2	-0.11	0.14	-9999	-0.29	427	427
PIK3CA	0.012	0.009	-9999	-0.29	1	1
JAK3	0.008	0.034	-9999	-0.29	14	14
PIK3R1	0.001	0.09	-9999	-0.79	14	14
JAK1	0.011	0.024	-9999	-0.79	1	1
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.057	0.08	-9999	-0.58	9	9
SHC1	0.012	0.001	-9999	-10000	0	0
SP1	-0.005	0.041	-9999	-0.38	13	13
IL2RA	0.001	0.13	-9999	-1	16	16
IL2RB	-0.001	0.066	-9999	-0.32	42	42
SOS1	0.012	0.001	-9999	-10000	0	0
IL2RG	-0.006	0.087	-9999	-0.36	53	53
G1/S transition of mitotic cell cycle	0.004	0.13	-9999	-0.8	24	24
PTPN11	0.012	0.001	-9999	-10000	0	0
CCND2	0.017	0.11	-9999	-1	13	13
LCK	-0.009	0.1	-9999	-0.41	53	53
GRB2	0.011	0.009	-9999	-0.29	1	1
IL2	0.004	0.026	-9999	-0.29	8	8
CDK6	-0.011	0.092	-9999	-0.73	17	17
CCND3	0.063	0.071	-9999	-0.57	5	5

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.005	0.035	-10000	0	-0.29	15	15
GNB1/GNG2	-0.015	0.048	-10000	0	-0.19	68	68
AKT1	0.05	0.072	-10000	0	-0.21	32	32
EGF	-0.15	0.31	-10000	0	-0.78	214	214
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	-0.01	0.053	-10000	0	-0.45	5	5
mol:Ca2+	0.047	0.1	-10000	0	-0.3	64	64
LYN	-0.01	0.05	-10000	0	-0.51	2	2
RhoA/GTP	-0.008	0.03	-10000	0	-0.14	7	7
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.052	0.11	-10000	0	-0.35	64	64
GNG2	-0.011	0.092	-10000	0	-0.79	15	15
ARRB2	0	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.028	0.063	-10000	0	-0.55	9	9
G beta5/gamma2	-0.019	0.065	-10000	0	-0.28	40	40
PRKCH	0.048	0.11	-10000	0	-0.35	64	64
DNM1	-0.005	0.063	-10000	0	-0.73	8	8
TXA2/TP beta/beta Arrestin3	-0.004	0.026	-10000	0	-0.3	7	7
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.031	0.15	-10000	0	-0.71	47	47
G12 family/GTP	-0.021	0.073	-10000	0	-0.31	64	64
ADRBK1	0	0	-10000	0	-10000	0	0
ADRBK2	-0.004	0.053	-10000	0	-0.79	5	5
RhoA/GTP/ROCK1	0	0.016	-10000	0	-0.52	1	1
mol:GDP	-0.036	0.081	0.36	23	-10000	0	23
mol:NADP	0	0	-10000	0	-10000	0	0
RAB11A	-0.001	0.013	-10000	0	-0.29	2	2
PRKG1	-0.053	0.2	-10000	0	-0.79	74	74
mol:IP3	0.047	0.12	-10000	0	-0.38	64	64
cell morphogenesis	0	0.016	-10000	0	-0.52	1	1
PLCB2	0.044	0.15	-10000	0	-0.52	64	64
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.008	0.062	-10000	0	-0.41	8	8
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.011	0.051	-10000	0	-0.51	2	2
RHOA	0	0	-10000	0	-10000	0	0
PTGIR	-0.002	0.026	-10000	0	-0.29	9	9
PRKCB1	0.045	0.12	-10000	0	-0.38	64	64
GNAQ	-0.002	0.041	-10000	0	-0.79	3	3
mol:L-citrulline	0	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.047	0.16	-10000	0	-0.54	64	64
LCK	-0.015	0.071	-10000	0	-0.46	16	16
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.012	0.056	-10000	0	-0.35	1	1
TXA2-R family/G12 family/GDP/G beta/gamma	0.024	0.037	-10000	0	-0.29	9	9
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.011	0.055	-10000	0	-0.34	1	1
MAPK14	0.051	0.079	-10000	0	-0.23	64	64
TGM2/GTP	0.047	0.13	-10000	0	-0.43	64	64
MAPK11	0.051	0.082	-10000	0	-0.24	64	64
ARHGEF1	0.039	0.061	-10000	0	-0.18	37	37
GNAI2	0	0	-10000	0	-10000	0	0
JNK cascade	0.049	0.12	-10000	0	-0.4	64	64
RAB11/GDP	-0.001	0.012	-10000	0	-0.29	2	2
ICAM1	0.046	0.093	-10000	0	-0.28	64	64
cAMP biosynthetic process	0.043	0.12	-10000	0	-0.36	64	64
Gq family/GTP/EBP50	0.017	0.04	-10000	0	-0.32	5	5
actin cytoskeleton reorganization	0	0.016	-10000	0	-0.52	1	1
SRC	-0.01	0.05	-10000	0	-0.41	4	4
GNB5	0	0	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
EGF/EGFR	-0.028	0.1	-10000	0	-0.32	34	34
VCAM1	0.044	0.1	-10000	0	-0.32	64	64
TP beta/Gq family/GDP/G beta5/gamma2	0.028	0.063	-10000	0	-0.55	9	9
platelet activation	0.066	0.1	-10000	0	-0.31	64	64
PGI2/IP	-0.002	0.018	-10000	0	-10000	0	0
PRKACA	-0.014	0.07	-10000	0	-0.37	40	40
Gq family/GDP/G beta5/gamma2	0.026	0.065	-10000	0	-0.55	9	9
TXA2/TP beta/beta Arrestin2	-0.005	0.052	-10000	0	-0.65	7	7
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.01	0.07	-10000	0	-0.34	40	40
mol:DAG	0.046	0.13	-10000	0	-0.42	64	64
EGFR	-0.29	0.38	-10000	0	-0.78	410	410
TXA2/TP alpha	0.048	0.15	-10000	0	-0.5	64	64
Gq family/GTP	-0.004	0.036	-10000	0	-0.27	18	18
YES1	-0.01	0.051	-10000	0	-0.42	4	4
GNAI2/GTP	-0.012	0.058	-10000	0	-0.46	5	5
PGD2/DP	-0.024	0.12	-10000	0	-0.55	47	47
SLC9A3R1	-0.026	0.083	-10000	0	-0.29	97	97
FYN	-0.011	0.054	-10000	0	-0.43	6	6
mol:NO	0	0	-10000	0	-10000	0	0
GNA15	-0.003	0.033	-10000	0	-0.36	8	8
PGK/cGMP	-0.036	0.13	-10000	0	-0.52	74	74
RhoA/GDP	0	0	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.017	0.082	-10000	0	-0.56	15	15
NOS3	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	0.041	0.13	-10000	0	-0.38	72	72
PRKCB	0.043	0.12	-10000	0	-0.37	72	72
PRKCE	0.05	0.11	-10000	0	-0.35	64	64
PRKCD	0.048	0.12	-10000	0	-0.38	64	64
PRKCG	0.044	0.12	-10000	0	-0.39	64	64
muscle contraction	0.05	0.15	-10000	0	-0.5	64	64
PRKCZ	0.052	0.11	-10000	0	-0.35	64	64
ARR3	-0.002	0.025	-10000	0	-0.29	8	8
TXA2/TP beta	-0.013	0.065	-10000	0	-0.49	6	6
PRKCQ	0.037	0.14	-10000	0	-0.39	77	77
MAPKKK cascade	0.044	0.14	-10000	0	-0.48	64	64
SELE	0.038	0.12	-10000	0	-0.42	64	64
TP beta/GNAI2/GDP/G beta/gamma	-0.016	0.082	-10000	0	-0.56	15	15
ROCK1	-0.001	0.024	-10000	0	-0.79	1	1
GNA14	-0.013	0.084	-10000	0	-0.46	30	30
chemotaxis	0.046	0.18	-10000	0	-0.62	64	64
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	-0.003	0.048	-10000	0	-0.79	4	4
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.004	0.11	-10000	0	-0.44	36	36
IKBKB	0.015	0.053	-10000	0	-0.26	3	3
AKT1	0.002	0.082	0.24	2	-0.27	25	27
IKBKG	0.018	0.055	-10000	0	-0.28	3	3
CALM1	-0.011	0.092	-10000	0	-0.45	30	30
PIK3CA	0	0.009	-10000	0	-0.29	1	1
MAP3K1	-0.01	0.15	-10000	0	-0.66	32	32
MAP3K7	0	0.009	-10000	0	-0.29	1	1
mol:Ca2+	-0.019	0.097	-10000	0	-0.48	30	30
DOK1	-0.001	0.018	-10000	0	-0.29	4	4
AP-1	-0.041	0.11	-10000	0	-0.26	78	78
LYN	0	0.001	-10000	0	-10000	0	0
BLNK	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
BCR complex	-0.079	0.21	-10000	0	-0.62	119	119
CD22	-0.061	0.18	-10000	0	-0.54	100	100
CAMK2G	-0.002	0.086	-10000	0	-0.42	29	29
CSNK2A1	0	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.047	0.13	-10000	0	-0.76	16	16
GO:0007205	-0.02	0.098	-10000	0	-0.49	30	30
SYK	0	0.009	-10000	0	-0.29	1	1
ELK1	-0.011	0.093	-10000	0	-0.46	30	30
NFATC1	-0.018	0.13	-10000	0	-0.56	34	34
B-cell antigen/BCR complex	-0.079	0.21	-10000	0	-0.62	119	119
PAG1/CSK	-0.001	0.013	-10000	0	-10000	0	0
NFKBIB	0.015	0.02	-10000	0	-10000	0	0
HRAS	-0.009	0.1	-10000	0	-0.47	31	31
NFKBIA	0.015	0.02	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.019	0.016	-10000	0	-10000	0	0
RasGAP/Csk	-0.058	0.16	-10000	0	-0.51	100	100
mol:GDP	-0.02	0.09	-10000	0	-0.46	30	30
PTEN	-0.001	0.034	-10000	0	-0.79	2	2
CD79B	-0.027	0.13	-10000	0	-0.58	52	52
NF-kappa-B/RelA/I kappa B alpha	0.019	0.016	-10000	0	-10000	0	0
GRB2	0	0.009	-10000	0	-0.29	1	1
PI3K/BCAP/CD19	-0.029	0.16	-10000	0	-0.47	101	101
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
mol:IP3	-0.029	0.096	-10000	0	-0.5	30	30
CSK	0	0	-10000	0	-10000	0	0
FOS	-0.13	0.22	-10000	0	-0.44	349	349
CHUK	0.018	0.055	-10000	0	-0.28	3	3
IBTK	0	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.023	0.077	-10000	0	-0.48	18	18
PTPN6	-0.057	0.16	-10000	0	-0.72	41	41
RELA	0	0	-10000	0	-10000	0	0
BCL2A1	0.015	0.02	-10000	0	-0.12	1	1
VAV2	-0.071	0.16	-10000	0	-0.6	62	62
ubiquitin-dependent protein catabolic process	0.019	0.019	-10000	0	-10000	0	0
BTK	-0.004	0.005	-10000	0	-10000	0	0
CD19	-0.081	0.17	-10000	0	-0.53	97	97
MAP4K1	-0.015	0.07	-10000	0	-0.31	53	53
CD72	-0.009	0.054	-10000	0	-0.31	32	32
PAG1	-0.001	0.02	-10000	0	-0.29	5	5
MAPK14	0.002	0.13	-10000	0	-0.54	31	31
SH3BP5	-0.001	0.024	-10000	0	-0.79	1	1
PIK3AP1	-0.01	0.1	0.27	1	-0.53	30	31
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.041	0.13	-10000	0	-0.47	85	85
RAF1	0	0.096	-10000	0	-0.44	30	30
RasGAP/p62DOK/SHIP	-0.055	0.15	-10000	0	-0.49	100	100
CD79A	-0.083	0.22	-10000	0	-0.53	171	171
re-entry into mitotic cell cycle	-0.04	0.11	-10000	0	-0.26	75	75
RASA1	0	0	-10000	0	-10000	0	0
MAPK3	0.016	0.082	-10000	0	-0.42	17	17
MAPK1	0.016	0.082	-10000	0	-0.42	17	17
CD72/SHP1	-0.055	0.15	-10000	0	-0.68	41	41
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.001	0.13	-10000	0	-0.53	37	37
actin cytoskeleton organization	-0.027	0.15	-10000	0	-0.64	33	33
NF-kappa-B/RelA	0.042	0.033	-10000	0	-10000	0	0
Calcineurin	-0.02	0.07	-10000	0	-0.44	17	17
PI3K	-0.06	0.13	-10000	0	-0.53	44	44
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.031	0.11	0.27	1	-0.57	30	31
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.048	0.17	-10000	0	-0.83	35	35
DAPP1	-0.05	0.19	-10000	0	-0.98	34	34
cytokine secretion	-0.015	0.12	-10000	0	-0.52	34	34
mol:DAG	-0.029	0.096	-10000	0	-0.5	30	30
PLCG2	-0.002	0.035	-10000	0	-0.62	3	3
MAP2K1	0.008	0.089	-10000	0	-0.48	17	17
B-cell antigen/BCR complex/FcgammaRIIB	-0.07	0.19	-10000	0	-0.6	100	100
mol:PI-3-4-5-P3	-0.044	0.093	0.34	2	-0.36	44	46
ETS1	0.004	0.089	-10000	0	-0.48	21	21
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.056	0.16	-10000	0	-0.51	97	97
B-cell antigen/BCR complex/LYN	-0.057	0.18	-10000	0	-0.57	97	97
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0.001	0.003	-10000	0	-10000	0	0
RAC1	-0.03	0.16	-10000	0	-0.71	33	33
B-cell antigen/BCR complex/LYN/SYK	-0.057	0.17	-10000	0	-0.55	98	98
CARD11	-0.014	0.1	-10000	0	-0.48	30	30
FCGR2B	-0.004	0.054	-10000	0	-0.7	6	6
PPP3CA	-0.001	0.013	-10000	0	-0.29	2	2
BCL10	0	0	-10000	0	-10000	0	0
IKK complex	0.017	0.027	-10000	0	-10000	0	0
PTPRC	-0.008	0.07	-10000	0	-0.48	19	19
PDPK1	-0.029	0.063	0.22	2	-0.26	25	27
PPP3CB	0	0	-10000	0	-10000	0	0
PPP3CC	0	0	-10000	0	-10000	0	0
POU2F2	0.019	0.014	-10000	0	-0.14	1	1

×

Aurora A signaling

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
Aurora A/GADD45A	-0.026	0.031	-9999	-10000	0	0
BIRC5	-0.21	0.13	-9999	-0.29	780	780
NFKBIA	-0.024	0.034	-9999	-10000	0	0
CPEB1	-0.15	0.31	-9999	-0.78	204	204
AKT1	-0.024	0.034	-9999	-10000	0	0
NDEL1	0	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.024	0.033	-9999	-0.55	1	1
NDEL1/TACC3	-0.041	0.061	-9999	-10000	0	0
GADD45A	0	0	-9999	-10000	0	0
GSK3B	0.003	0.004	-9999	-10000	0	0
PAK1/Aurora A	-0.03	0.04	-9999	-10000	0	0
MDM2	-0.001	0.02	-9999	-0.29	5	5
JUB	-0.003	0.048	-9999	-0.79	4	4
TPX2	-0.11	0.1	-9999	-10000	0	0
TP53	-0.011	0.017	-9999	-10000	0	0
DLG7	-0.03	0.037	-9999	-10000	0	0
AURKAIP1	-0.003	0.031	-9999	-0.29	12	12
ARHGEF7	0	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.043	0.065	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.024	0.033	-9999	-0.54	1	1
AURKA	-0.037	0.046	-9999	-10000	0	0
AURKB	-0.009	0.011	-9999	-10000	0	0
CDC25B	-0.018	0.026	-9999	-10000	0	0
G2/M transition checkpoint	-0.025	0.04	-9999	-0.49	4	4
mRNA polyadenylation	-0.11	0.19	-9999	-0.52	203	203
Aurora A/CPEB	-0.11	0.2	-9999	-0.52	203	203
Aurora A/TACC1/TRAP/chTOG	-0.032	0.089	-9999	-0.47	42	42
BRCA1	-0.001	0.027	-9999	-0.46	3	3
centrosome duplication	-0.03	0.039	-9999	-10000	0	0
regulation of centrosome cycle	-0.04	0.061	-9999	-10000	0	0
spindle assembly	-0.032	0.088	-9999	-0.46	42	42
TDRD7	0	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.1	0.072	-9999	-0.61	1	1
CENPA	-0.006	0.012	-9999	-10000	0	0
Aurora A/PP2A	-0.026	0.031	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.006	0.029	-9999	-10000	0	0
negative regulation of DNA binding	-0.009	0.02	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	-0.001	0.013	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.025	0.04	-9999	-0.49	4	4
mitotic prometaphase	-0.013	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.037	0.046	-9999	-10000	0	0
TACC1	-0.03	0.15	-9999	-0.79	42	42
TACC3	-0.046	0.11	-9999	-0.29	173	173
Aurora A/Antizyme1	-0.022	0.025	-9999	-10000	0	0
Aurora A/RasGAP	-0.026	0.031	-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	0.003	0.004	-9999	-10000	0	0
GIT1	-0.001	0.02	-9999	-0.29	5	5
GIT1/beta-PIX/PAK1	-0.004	0.023	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.11	0.1	-9999	-10000	0	0
PPP2R5D	0	0	-9999	-10000	0	0
Aurora A/TPX2	-0.11	0.09	-9999	-10000	0	0
PAK1	-0.007	0.044	-9999	-0.29	25	25
CKAP5	0	0	-9999	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.44	0.39	-10000	0	-0.79	610	610
CLTC	0.027	0.018	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.024	0.02	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.007	0.028	-10000	0	-10000	0	0
EXOC4	0	0	-10000	0	-10000	0	0
CD59	0.025	0.019	-10000	0	-10000	0	0
CPE	0.006	0.081	-10000	0	-0.53	25	25
CTNNB1	0	0	-10000	0	-10000	0	0
membrane fusion	-0.002	0.019	-10000	0	-10000	0	0
CTNND1	0.025	0.032	-10000	0	-10000	0	0
DNM2	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.029	0.014	-10000	0	-10000	0	0
TSHR	-0.007	0.11	-10000	0	-0.53	49	49
INS	0.011	0.005	-10000	0	-10000	0	0
BIN1	-0.007	0.072	-10000	0	-0.79	9	9
mol:Choline	-0.002	0.019	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.009	0.038	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.007	0.028	-10000	0	-10000	0	0
JUP	0.025	0.017	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.004	0.045	-10000	0	-0.48	10	10
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.018	0.049	-10000	0	-0.37	1	1
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0	0.009	-10000	0	-0.29	1	1
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	-0.005	0.037	-10000	0	-0.29	18	18
substrate adhesion-dependent cell spreading	0	0.001	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.008	0.032	-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	0.019	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.02	0.015	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.032	0.022	-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	0.025	0.031	-10000	0	-10000	0	0
NME1	0.009	0.038	-10000	0	-10000	0	0
clathrin coat assembly	0.027	0.018	-10000	0	-10000	0	0
IL2RA	0.017	0.045	-10000	0	-0.37	7	7
VAMP3	0.018	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.22	0.2	-10000	0	-0.39	610	610
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	-0.003	0.032	-10000	0	-0.34	10	10
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0	0	-10000	0	-10000	0	0
PIP5K1C	0.03	0.014	-10000	0	-10000	0	0
SDC1	0.021	0.024	-10000	0	-0.35	1	1
ARF6/GDP	-0.008	0.034	-10000	0	-10000	0	0
EXOC7	0	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.008	0.033	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.002	0.019	-10000	0	-10000	0	0
endocytosis	0.004	0.045	0.47	10	-10000	0	10
SCAMP2	0	0	-10000	0	-10000	0	0
ADRB2	-0.071	0.19	-10000	0	-0.42	253	253
EXOC3	0	0	-10000	0	-10000	0	0
ASAP2	-0.001	0.024	-10000	0	-0.79	1	1
Dynamin 2/GDP	-0.007	0.028	-10000	0	-10000	0	0
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	-0.13	0.22	-10000	0	-0.42	397	397
RALA	0	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.007	0.028	-10000	0	-10000	0	0

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.025	0.079	-9999	-0.2	188	188
TP53	-0.008	0.02	-9999	-10000	0	0
Senescence	-0.008	0.02	-9999	-10000	0	0
Apoptosis	-0.008	0.02	-9999	-10000	0	0
Activated_Oncogenes	0	0	-9999	-10000	0	0
MDM2	0.017	0.041	-9999	-10000	0	0
MDM4	0	0	-9999	-10000	0	0

×

S1P5 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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.024	0.077	0.32	36	-10000	0	36
GNAI2	0	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.005	0.035	-10000	0	-0.52	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.03	0.13	-10000	0	-0.48	67	67
RhoA/GTP	-0.025	0.078	-10000	0	-0.32	36	36
negative regulation of cAMP metabolic process	-0.028	0.087	-10000	0	-0.3	96	96
GNAZ	-0.007	0.075	-10000	0	-0.79	10	10
GNAI3	0	0	-10000	0	-10000	0	0
GNA12	0	0	-10000	0	-10000	0	0
S1PR5	-0.008	0.058	-10000	0	-0.35	25	25
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.028	0.088	-10000	0	-0.3	96	96
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
GNAI1	-0.045	0.18	-10000	0	-0.79	62	62

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.011	0.079	-10000	0	-0.6	19	19
ATM	0	0	-10000	0	-10000	0	0
UBE2D3	0	0	-10000	0	-10000	0	0
PRKDC	-0.001	0.018	-10000	0	-0.29	4	4
ATR	0	0	-10000	0	-10000	0	0
UBE2L3	0	0	-10000	0	-10000	0	0
FANCD2	0.024	0.01	-10000	0	-10000	0	0
protein ubiquitination	-0.029	0.073	-10000	0	-0.47	20	20
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	0.001	0.011	-10000	0	-10000	0	0
FANCF	0	0.009	-10000	0	-0.29	1	1
BRCA1	-0.001	0.027	-10000	0	-0.46	3	3
CCNE1	-0.06	0.12	-10000	0	-0.29	223	223
CDK2/Cyclin E1	-0.038	0.075	-10000	0	-10000	0	0
FANCG	0	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.011	0.081	-10000	0	-0.6	20	20
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	-0.051	0.11	-10000	0	-0.29	192	192
DNA repair	0.008	0.094	-10000	0	-0.47	6	6
BRCA1/BARD1/ubiquitin	-0.011	0.081	-10000	0	-0.6	20	20
BARD1/DNA-PK	-0.009	0.062	-10000	0	-0.47	19	19
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.011	0.079	0.6	19	-10000	0	19
BRCA1/BARD1/CTIP/M/R/N Complex	-0.006	0.041	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	-0.01	0.07	-10000	0	-0.52	20	20
BRCA1/BARD1/P53	-0.009	0.063	-10000	0	-0.47	20	20
BARD1/CSTF1/BRCA1	-0.01	0.07	-10000	0	-0.52	20	20
BRCA1/BACH1	-0.001	0.027	-10000	0	-0.46	3	3
BARD1	-0.014	0.1	-10000	0	-0.76	20	20
PCNA	-0.001	0.015	-10000	0	-0.29	3	3
BRCA1/BARD1/UbcH5C	-0.01	0.07	-10000	0	-0.52	20	20
BRCA1/BARD1/UbcH7	-0.01	0.07	-10000	0	-0.52	20	20
BRCA1/BARD1/RAD51/PCNA	-0.053	0.086	-10000	0	-0.51	20	20
BARD1/DNA-PK/P53	-0.008	0.057	-10000	0	-0.44	19	19
BRCA1/BARD1/Ubiquitin	-0.011	0.081	-10000	0	-0.6	20	20
BRCA1/BARD1/CTIP	-0.009	0.063	-10000	0	-0.47	20	20
FA complex	-0.005	0.011	-10000	0	-10000	0	0
BARD1/EWS	-0.011	0.079	-10000	0	-0.6	19	19
RBBP8	0.022	0.006	-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	0.009	0.063	0.46	20	-10000	0	20
BRCA1/BARD1	-0.029	0.074	-10000	0	-0.48	20	20
CSTF1	0	0.009	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.011	0.08	-10000	0	-0.61	19	19
CDK2	0	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.11	0.14	-10000	0	-0.29	396	396
RAD50	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.011	0.081	-10000	0	-0.6	20	20
EWSR1	0	0	-10000	0	-10000	0	0

×

Glypican 2 network

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
MDK	-0.012	0.057	-9999	-0.29	43	43
GPC2	-0.038	0.1	-9999	-0.79	3	3
GPC2/Midkine	-0.032	0.081	-9999	-0.4	19	19
neuron projection morphogenesis	-0.032	0.081	-9999	-0.4	19	19

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.03	0.13	-9999	-0.48	67	67
CDC42/GTP	-0.026	0.077	-9999	-0.31	40	40
PLCG1	0.008	0.092	-9999	-0.32	40	40
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	0.076	-9999	-0.3	40	40
S1PR5	-0.008	0.058	-9999	-0.35	25	25
S1PR4	-0.014	0.079	-9999	-0.36	44	44
MAPK3	0.008	0.092	-9999	-0.5	4	4
MAPK1	0.008	0.092	-9999	-0.32	40	40
S1P/S1P5/Gi	-0.028	0.088	-9999	-0.3	96	96
GNAI1	-0.045	0.18	-9999	-0.79	62	62
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.005	0.035	-9999	-0.52	3	3
RHOA	-0.006	0.038	-9999	-0.44	6	6
S1P/S1P4/Gi	-0.029	0.087	-9999	-0.34	40	40
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.007	0.075	-9999	-0.79	10	10
S1P/S1P4/G12/G13	-0.007	0.042	-9999	-0.48	6	6
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.001	0.004	-9999	-10000	0	0
HDAC2	0.001	0.004	-9999	-10000	0	0
GNB1/GNG2	-0.011	0.081	-9999	-0.56	22	22
forebrain development	-0.024	0.2	-9999	-0.51	136	136
GNAO1	-0.021	0.13	-9999	-0.48	67	67
SMO/beta Arrestin2	-0.005	0.055	-9999	-0.6	9	9
SMO	0.004	0.073	-9999	-0.79	9	9
ARRB2	0.011	0.004	-9999	-10000	0	0
GLI3/SPOP	0.044	0.037	-9999	-10000	0	0
mol:GTP	0	0.003	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
GNAI2	0.01	0.004	-9999	-10000	0	0
SIN3/HDAC complex	0	0.007	-9999	-10000	0	0
GNAI1	-0.035	0.18	-9999	-0.79	62	62
XPO1	0.012	0.004	-9999	-10000	0	0
GLI1/Su(fu)	-0.054	0.16	-9999	-0.67	37	37
SAP30	0	0.018	-9999	-0.29	4	4
mol:GDP	0.004	0.073	-9999	-0.79	9	9
MIM/GLI2A	0.002	0.028	-9999	-0.3	9	9
IFT88	0	0	-9999	-10000	0	0
GNAI3	0.01	0.004	-9999	-10000	0	0
GLI2	0.04	0.037	-9999	-10000	0	0
GLI3	0.04	0.039	-9999	-0.3	10	10
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
SAP18	0.001	0.004	-9999	-10000	0	0
embryonic digit morphogenesis	0	0	-9999	-10000	0	0
GNG2	-0.011	0.092	-9999	-0.79	15	15
Gi family/GTP	-0.002	0.1	-9999	-0.36	50	50
SIN3B	0.001	0.004	-9999	-10000	0	0
SIN3A	0.001	0.004	-9999	-10000	0	0
GLI3/Su(fu)	-0.002	0.025	-9999	-0.44	1	1
GLI2/Su(fu)	0.008	0.048	-9999	-0.39	7	7
FOXA2	-0.012	0.031	-9999	-10000	0	0
neural tube patterning	-0.024	0.2	-9999	-0.51	136	136
SPOP	0	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.002	0.026	-9999	-0.45	1	1
GNB1	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
CSNK1G3	0	0	-9999	-10000	0	0
MTSS1	0.002	0.028	-9999	-0.3	9	9
embryonic limb morphogenesis	-0.024	0.2	-9999	-0.51	136	136
SUFU	0.004	0.032	-9999	-0.5	1	1
LGALS3	-0.012	0.095	-9999	-0.79	16	16
catabolic process	-0.004	0.027	-9999	-10000	0	0
GLI3A/CBP	-0.008	0.097	-9999	-0.38	70	70
KIF3A	0	0	-9999	-10000	0	0
GLI1	-0.026	0.21	-9999	-0.52	136	136
RAB23	0	0	-9999	-10000	0	0
CSNK1A1	0	0	-9999	-10000	0	0
IFT172	-0.001	0.024	-9999	-0.79	1	1
RBBP7	-0.001	0.025	-9999	-0.29	8	8
Su(fu)/Galectin3	-0.009	0.067	-9999	-0.51	17	17
GNAZ	0.003	0.076	-9999	-0.79	10	10
RBBP4	0.001	0.024	-9999	-0.79	1	1
CSNK1G1	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GLI2/SPOP	-0.004	0.027	-9999	-10000	0	0
STK36	0.011	0.024	-9999	-0.79	1	1
Gi family/GNB1/GNG2/GDP	-0.031	0.1	-9999	-0.57	18	18
PTCH1	-0.067	0.34	-9999	-1.1	95	95
MIM/GLI1	-0.018	0.19	-9999	-0.57	74	74
CREBBP	-0.008	0.097	-9999	-0.38	70	70
Su(fu)/SIN3/HDAC complex	0.008	0.023	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.022	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0.007	-10000	0	-10000	0	0
CDKN1B	0.036	0.024	-10000	0	-0.42	3	3
CDKN1A	0.036	0.02	-10000	0	-0.42	2	2
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	-0.001	0.018	-10000	0	-0.29	4	4
FOXO3	0.036	0.024	-10000	0	-0.42	3	3
AKT1	0	0.001	-10000	0	-10000	0	0
BAD	0	0.009	-10000	0	-0.29	1	1
AKT3	0.008	0.061	-10000	0	-0.44	20	20
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.037	0.003	-10000	0	-10000	0	0
AKT1/ASK1	-0.001	0.025	-10000	0	-0.41	4	4
BAD/YWHAZ	-0.001	0.009	-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	0.024	0.39	4	-10000	0	4
TSC1	0.037	0.003	-10000	0	-10000	0	0
YWHAZ	-0.001	0.015	-10000	0	-0.29	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	0.003	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
TBC1D4	0.022	0.04	-10000	0	-0.51	6	6
MAP3K5	-0.003	0.048	-10000	0	-0.79	4	4
MAPKAP1	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.04	0.022	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
AKT1S1	0.037	0.003	-10000	0	-10000	0	0
CASP9	0.037	0.003	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	-0.001	0.021	-10000	0	-0.39	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	-0.29	1	1
AKT2/p21CIP1	-0.001	0.017	-10000	0	-0.4	2	2
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.018	0.001	-10000	0	-10000	0	0
CHUK	0.037	0.003	-10000	0	-10000	0	0
BAD/BCL-XL	0	0.003	-10000	0	-10000	0	0
mTORC2	0	0	-10000	0	-10000	0	0
AKT2	0.017	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	0.01	-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	0.044	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0.005	-10000	0	-10000	0	0
glucose import	-0.25	0.25	-10000	0	-0.47	612	612
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	-0.25	0.25	-10000	0	-0.47	612	612
GSK3A	0.037	0.003	-10000	0	-10000	0	0
FOXO1	0.032	0.048	-10000	0	-0.42	12	12
GSK3B	0.037	0.003	-10000	0	-10000	0	0
SFN	-0.016	0.099	-10000	0	-0.5	36	36
G1/S transition of mitotic cell cycle	0.044	0.003	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.042	0.032	-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	-0.29	1	1
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.022	0.02	-10000	0	-0.6	1	1
MAP4K4	0.041	0.044	-10000	0	-0.68	1	1
BAG4	-0.006	0.055	-10000	0	-0.43	14	14
PKC zeta/ceramide	-0.023	0.047	0.18	1	-0.57	1	2
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.077	-10000	0	-0.5	21	21
BAX	-0.008	0.021	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
AKT1	0.024	0.009	-10000	0	-10000	0	0
BAD	-0.021	0.045	0.2	1	-0.25	1	2
SMPD1	0.026	0.032	-10000	0	-0.24	13	13
RB1	-0.022	0.047	0.2	1	-0.47	1	2
FADD/Caspase 8	0.049	0.046	-10000	0	-0.64	1	1
MAP2K4	-0.014	0.046	-10000	0	-0.44	2	2
NSMAF	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.014	0.045	-10000	0	-0.45	1	1
EGF	-0.15	0.31	-10000	0	-0.78	214	214
mol:ceramide	-0.033	0.047	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	0.023	-10000	0	-0.6	1	1
ASAH1	-0.001	0.015	-10000	0	-0.29	3	3
negative regulation of cell cycle	-0.022	0.046	0.2	1	-0.46	1	2
cell proliferation	-0.094	0.16	-10000	0	-0.38	247	247
BID	0.024	0.033	-10000	0	-0.39	1	1
MAP3K1	-0.022	0.047	0.2	1	-0.47	1	2
EIF2A	-0.005	0.04	-10000	0	-10000	0	0
TRADD	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
MAPK3	-0.001	0.043	-10000	0	-0.41	1	1
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.001	0.043	-10000	0	-0.41	1	1
Cathepsin D/ceramide	-0.027	0.049	0.18	1	-0.25	2	3
FADD	0.04	0.048	-10000	0	-0.47	3	3
KSR1	-0.022	0.048	0.2	1	-0.32	3	4
MAPK8	-0.012	0.054	0.2	1	-0.34	11	12
PRKRA	-0.021	0.045	0.2	1	-10000	0	1
PDGFA	-0.001	0.025	-10000	0	-0.54	2	2
TRAF2	-0.001	0.018	-10000	0	-0.29	4	4
IGF1	-0.18	0.33	-10000	0	-0.79	247	247
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.032	0.047	0.21	1	-10000	0	1
CTSD	-0.01	0.053	-10000	0	-0.29	37	37
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	0.17	-10000	0	-0.41	247	247
PRKCD	0	0.009	-10000	0	-0.29	1	1
PRKCZ	-0.001	0.024	-10000	0	-0.79	1	1
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.021	0.023	-10000	0	-0.6	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	0.024	-10000	0	-0.79	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.006	0.04	-10000	0	-0.72	1	1
TNFR1A/BAG4/TNF-alpha	-0.013	0.069	-10000	0	-0.52	17	17
mol:Sphingosine-1-phosphate	0.022	0.02	-10000	0	-0.6	1	1
MAP2K1	-0.005	0.043	-10000	0	-0.42	1	1
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
CYCS	-0.007	0.043	0.18	25	-10000	0	25
TNFRSF1A	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.004	0.04	-10000	0	-0.6	4	4
EIF2AK2	-0.013	0.042	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.009	0.06	-10000	0	-0.52	13	13
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.002	0.02	-10000	0	-0.32	1	1
MAP2K2	-0.005	0.043	-10000	0	-0.42	1	1
SMPD3	0.026	0.039	-10000	0	-0.27	16	16
TNF	-0.016	0.095	-10000	0	-0.46	38	38
PKC zeta/PAR4	-0.001	0.026	-10000	0	-0.6	2	2
mol:PHOSPHOCHOLINE	0.044	0.11	0.27	213	-10000	0	213
NF kappa B1/RelA/I kappa B alpha	-0.001	0.019	-10000	0	-0.43	2	2
AIFM1	-0.007	0.043	0.18	25	-10000	0	25
BCL2	-0.027	0.14	-10000	0	-0.79	37	37

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.007	0.072	-10000	0	-0.74	10	10
positive regulation of NF-kappaB transcription factor activity	-0.062	0.18	-10000	0	-0.6	113	113
MAP2K4	0.042	0.038	-10000	0	-0.42	1	1
IKBKB	-0.001	0.013	-10000	0	-0.29	2	2
TNFRSF10B	0	0	-10000	0	-10000	0	0
TNFRSF10A	-0.005	0.063	-10000	0	-0.79	7	7
SMPD1	-0.002	0.026	-10000	0	-0.28	9	9
IKBKG	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.075	0.23	-10000	0	-0.79	104	104
TRAIL/TRAILR2	-0.005	0.054	-10000	0	-0.6	9	9
TRAIL/TRAILR3	-0.008	0.068	-10000	0	-0.64	11	11
TRAIL/TRAILR1	-0.009	0.072	-10000	0	-0.6	16	16
TRAIL/TRAILR4	-0.062	0.18	-10000	0	-0.6	113	113
TRAIL/TRAILR1/DAP3/GTP	-0.007	0.057	-10000	0	-0.48	16	16
IKK complex	-0.003	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	-0.2	1	1
MAPK3	0.017	0.056	-10000	0	-0.6	9	9
MAP3K1	-0.004	0.032	-10000	0	-0.32	10	10
TRAILR4 (trimer)	-0.075	0.23	-10000	0	-0.79	104	104
TRADD	0	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	-0.005	0.063	-10000	0	-0.79	7	7
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.005	0.039	-10000	0	-0.32	16	16
CFLAR	-0.001	0.024	-10000	0	-0.79	1	1
MAPK1	0.017	0.056	-10000	0	-0.6	9	9
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.008	0.055	-10000	0	-0.44	16	16
mol:ceramide	-0.002	0.025	-10000	0	-0.28	9	9
FADD	-0.004	0.034	-10000	0	-0.29	15	15
MAPK8	0.044	0.057	-10000	0	-0.43	10	10
TRAF2	-0.001	0.018	-10000	0	-0.29	4	4
TRAILR3 (trimer)	-0.004	0.048	-10000	0	-0.43	11	11
CHUK	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.01	0.065	-10000	0	-0.52	16	16
DAP3	0	0.009	-10000	0	-0.29	1	1
CASP10	0.021	0.11	0.31	98	-0.49	13	111
JNK cascade	-0.062	0.18	-10000	0	-0.6	113	113
TRAIL (trimer)	-0.007	0.072	-10000	0	-0.74	10	10
TNFRSF10C	-0.004	0.048	-10000	0	-0.43	11	11
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.008	0.056	-10000	0	-0.45	16	16
TRAIL/TRAILR2/FADD	-0.006	0.05	-10000	0	-0.52	9	9
cell death	-0.002	0.025	-10000	0	-0.28	9	9
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.003	0.029	-10000	0	-0.32	9	9
TRAILR2 (trimer)	0	0	-10000	0	-10000	0	0
CASP8	0.001	0.016	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.005	0.041	-10000	0	-0.44	9	9

×

Retinoic acid receptors-mediated signaling

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	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	0.016	-10000	0	-0.52	1	1
EP300	0	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.037	0.043	-10000	0	-0.34	6	6
KAT2B	-0.001	0.024	-10000	0	-0.79	1	1
MAPK14	0	0	-10000	0	-10000	0	0
AKT1	0.019	0.054	0.24	4	-0.36	14	18
RAR alpha/9cRA/Cyclin H	-0.012	0.067	-10000	0	-0.39	29	29
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.033	0.052	-10000	0	-0.41	8	8
CDC2	0.001	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.013	0.074	-10000	0	-0.66	10	10
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	0.13	-10000	0	-0.58	35	35
NCOA2	-0.039	0.17	-10000	0	-0.79	54	54
NCOA3	0	0.009	-10000	0	-0.29	1	1
NCOA1	-0.001	0.024	-10000	0	-0.79	1	1
VDR/VDR/DNA	0	0	-10000	0	-10000	0	0
RARG	0.012	0.001	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0.011	0.002	-10000	0	-10000	0	0
MAPK1	0	0	-10000	0	-10000	0	0
MAPK8	0.006	0.072	-10000	0	-0.79	9	9
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.042	0.11	-10000	0	-0.63	29	29
RARA	0.014	0.066	-10000	0	-0.32	36	36
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.019	0.09	-10000	0	-0.42	21	21
PRKCA	-0.007	0.13	-10000	0	-0.75	31	31
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.006	0.14	-10000	0	-0.6	36	36
RXRG	-0.1	0.21	-10000	0	-0.44	290	290
RXRA	0.021	0.067	-10000	0	-0.33	36	36
RXRB	0.01	0.076	-10000	0	-0.43	29	29
VDR/Vit D3/DNA	0	0	-10000	0	-10000	0	0
RBP1	-0.026	0.097	-10000	0	-0.33	86	86
CRBP1/9-cic-RA	-0.018	0.07	-10000	0	-0.23	86	86
RARB	0.002	0.093	-10000	0	-0.79	15	15
PRKCG	-0.003	0.062	-10000	0	-0.29	49	49
MNAT1	0	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.009	0.13	-10000	0	-0.62	33	33
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.012	0.11	-10000	0	-0.51	34	34
proteasomal ubiquitin-dependent protein catabolic process	0.035	0.062	-10000	0	-0.48	7	7
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.006	0.14	-10000	0	-0.6	36	36
positive regulation of DNA binding	-0.011	0.063	-10000	0	-0.37	29	29
NRIP1	-0.004	0.13	-10000	0	-0.64	24	24
RXRs/RARs	-0.013	0.13	-10000	0	-0.6	36	36
RXRs/RXRs/DNA/9cRA	-0.046	0.12	-10000	0	-0.65	30	30
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	-0.007	0.038	-10000	0	-0.53	2	2
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

×

Caspase cascade in apoptosis

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
TOP1	0.005	0.094	-10000	0	-0.44	38	38
ACTA1	-0.018	0.13	0.27	1	-0.64	36	37
NUMA1	0.005	0.094	0.23	1	-0.44	38	39
SPTAN1	-0.005	0.12	-10000	0	-0.61	35	35
LIMK1	-0.005	0.12	-10000	0	-0.61	35	35
BIRC3	-0.01	0.077	-10000	0	-0.5	21	21
BIRC2	0	0	-10000	0	-10000	0	0
BAX	-0.001	0.018	-10000	0	-0.29	4	4
CASP10	-0.015	0.14	-10000	0	-0.65	39	39
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.005	0.094	0.23	1	-0.44	38	39
DIABLO	0	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.004	0.12	-10000	0	-0.6	35	35
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
GSN	-0.011	0.14	-10000	0	-0.61	45	45
MADD	0	0	-10000	0	-10000	0	0
TFAP2A	0.014	0.083	-10000	0	-0.67	15	15
BID	0.005	0.062	-10000	0	-0.29	38	38
MAP3K1	0.004	0.042	-10000	0	-0.28	8	8
TRADD	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.005	0.12	-10000	0	-0.61	35	35
CASP9	0.002	0.004	-10000	0	-10000	0	0
DNA repair	-0.002	0.031	0.18	7	-0.22	4	11
neuron apoptosis	0.022	0.013	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.003	0.12	-10000	0	-0.58	35	35
APAF1	0.001	0.003	-10000	0	-10000	0	0
CASP6	0.023	0.057	-10000	0	-0.35	10	10
TRAF2	-0.001	0.018	-10000	0	-0.29	4	4
ICAD/CAD	0.003	0.12	-10000	0	-0.58	35	35
CASP7	-0.007	0.037	0.36	9	-10000	0	9
KRT18	0.015	0.024	-10000	0	-0.59	1	1
apoptosis	0.009	0.11	0.3	1	-0.51	35	36
DFFA	-0.005	0.12	-10000	0	-0.61	35	35
DFFB	-0.005	0.12	-10000	0	-0.61	35	35
PARP1	0.002	0.031	0.22	4	-0.18	7	11
actin filament polymerization	-0.002	0.12	0.55	39	-10000	0	39
TNF	-0.016	0.095	-10000	0	-0.46	38	38
CYCS	0.007	0.05	-10000	0	-0.21	38	38
SATB1	0.016	0.099	-10000	0	-0.46	34	34
SLK	-0.005	0.12	-10000	0	-0.61	35	35
p15 BID/BAX	-0.014	0.049	-10000	0	-0.35	8	8
CASP2	0.044	0.039	-10000	0	-0.45	1	1
JNK cascade	-0.004	0.042	0.27	8	-10000	0	8
CASP3	-0.014	0.13	0.28	1	-0.64	36	37
LMNB2	0.041	0.036	-10000	0	-0.33	3	3
RIPK1	0	0	-10000	0	-10000	0	0
CASP4	-0.001	0.024	-10000	0	-0.79	1	1
Mammalian IAPs/DIABLO	-0.005	0.044	-10000	0	-0.47	9	9
negative regulation of DNA binding	0.014	0.082	-10000	0	-0.66	15	15
stress fiber formation	-0.004	0.12	-10000	0	-0.6	35	35
GZMB	-0.029	0.15	-10000	0	-0.64	47	47
CASP1	0.014	0.033	-10000	0	-0.44	6	6
LMNB1	0.044	0.037	-10000	0	-0.38	2	2
APP	0.022	0.013	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.011	0	-10000	0	-10000	0	0
VIM	0.003	0.1	0.3	1	-0.5	35	36
LMNA	0.04	0.036	-10000	0	-0.38	2	2
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.005	0.034	-10000	0	-0.48	1	1
LRDD	-0.002	0.022	-10000	0	-0.29	6	6
SREBF1	-0.007	0.13	-10000	0	-0.61	35	35
APAF-1/Caspase 9	-0.004	0.02	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.005	0.092	0.23	1	-0.43	38	39
CFL2	0.001	0.12	-10000	0	-0.56	39	39
GAS2	-0.046	0.18	-10000	0	-0.52	126	126
positive regulation of apoptosis	0.045	0.036	-10000	0	-0.37	2	2
PRF1	-0.017	0.11	-10000	0	-0.79	20	20

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.03	0.007	-9999	-10000	0	0
SNTA1	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.017	0.046	-9999	-10000	0	0
MAPK12	0.017	0.082	-9999	-0.46	30	30
CCND1	0.015	0.043	-9999	-0.22	29	29
p38 gamma/SNTA1	-0.012	0.071	-9999	-0.42	30	30
MAP2K3	0	0.009	-9999	-0.29	1	1
PKN1	0	0.009	-9999	-0.29	1	1
G2/M transition checkpoint	0.017	0.082	-9999	-0.45	30	30
MAP2K6	0.01	0.084	-9999	-0.49	30	30
MAPT	-0.018	0.13	-9999	-0.4	117	117
MAPK13	0.022	0.009	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.014	0.031	-9999	-0.44	5	5

×

Cellular roles of Anthrax toxin

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.003	0.048	-10000	0	-0.69	5	5
ANTXR2	-0.009	0.082	-10000	0	-0.79	12	12
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.001	0.012	-10000	0	-0.1	14	14
monocyte activation	0.004	0.073	-10000	0	-0.46	26	26
MAP2K2	-0.001	0.005	-10000	0	-10000	0	0
MAP2K1	-0.001	0.01	-10000	0	-10000	0	0
MAP2K7	-0.001	0.01	-10000	0	-10000	0	0
MAP2K6	-0.012	0.071	-10000	0	-0.47	25	25
CYAA	0.009	0.062	-10000	0	-0.52	14	14
MAP2K4	-0.002	0.017	-10000	0	-0.46	1	1
IL1B	0.007	0.064	-10000	0	-0.34	31	31
Channel	-0.007	0.064	-10000	0	-0.55	14	14
NLRP1	-0.008	0.059	-10000	0	-0.49	16	16
CALM1	0	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.002	0.014	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.001	0.012	0.1	14	-10000	0	14
MAPK3	-0.001	0.01	-10000	0	-10000	0	0
MAPK1	-0.001	0.01	-10000	0	-10000	0	0
PGR	-0.14	0.21	-10000	0	-0.47	313	313
PA/Cellular Receptors	-0.008	0.069	-10000	0	-0.59	14	14
apoptosis	-0.001	0.012	-10000	0	-0.1	14	14
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.007	0.06	-10000	0	-0.51	14	14
macrophage activation	0.019	0.011	-10000	0	-10000	0	0
TNF	-0.016	0.095	-10000	0	-0.46	38	38
VCAM1	-0.011	0.071	-10000	0	-0.46	26	26
platelet activation	-0.002	0.014	-10000	0	-10000	0	0
MAPKKK cascade	-0.013	0.022	0.17	4	-10000	0	4
IL18	0.01	0.037	-10000	0	-0.22	16	16
negative regulation of macrophage activation	-0.001	0.012	-10000	0	-0.1	14	14
LEF	-0.001	0.012	-10000	0	-0.1	14	14
CASP1	-0.005	0.031	-10000	0	-0.23	17	17
mol:cAMP	-0.002	0.014	-10000	0	-10000	0	0
necrosis	-0.001	0.012	-10000	0	-0.1	14	14
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.007	0.061	-10000	0	-0.52	14	14
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.045	0.065	-10000	0	-0.57	2	2
UGCG	-0.011	0.095	-10000	0	-0.79	15	15
AKT1/mTOR/p70S6K/Hsp90/TERT	0.054	0.091	-10000	0	-0.39	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.013	0.097	-10000	0	-0.78	15	15
mol:DAG	0	0.002	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.026	0.09	-10000	0	-0.37	55	55
FRAP1	0.052	0.13	-10000	0	-0.41	67	67
FOXO3	0.06	0.11	-10000	0	-0.41	37	37
AKT1	0.055	0.11	-10000	0	-0.45	34	34
GAB2	0.008	0.043	-10000	0	-0.39	10	10
SMPD1	-0.002	0.014	-10000	0	-10000	0	0
SGMS1	-0.002	0.014	-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	0.015	0.062	-10000	0	-0.52	14	14
CALM1	0	0	-10000	0	-10000	0	0
cell proliferation	0.032	0.089	-10000	0	-0.35	39	39
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	-0.008	0.068	-10000	0	-0.6	14	14
RPS6KB1	0.021	0.034	-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	10	10
JAK3	0.01	0.034	-10000	0	-0.29	14	14
PIK3R1	0.003	0.09	-10000	0	-0.79	14	14
JAK1	0.013	0.024	-10000	0	-0.78	1	1
NFKB1	0	0	-10000	0	-10000	0	0
MYC	0.046	0.18	-10000	0	-0.92	30	30
MYB	0.006	0.19	-10000	0	-1.3	23	23
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.052	0.094	-10000	0	-0.56	11	11
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.004	0.023	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.052	0.092	-10000	0	-0.54	11	11
Rac1/GDP	-0.006	0.053	-10000	0	-0.47	14	14
T cell proliferation	0.058	0.087	-10000	0	-0.5	11	11
SHC1	0.011	0.003	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.01	-10000	0	-0.066	23	23
PRKCZ	0.058	0.09	-10000	0	-0.53	11	11
NF kappa B1 p50/RelA	-0.025	0.088	-10000	0	-0.49	15	15
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.039	0.07	-10000	0	-0.52	6	6
HSP90AA1	0	0.009	-10000	0	-0.29	1	1
RELA	0	0	-10000	0	-10000	0	0
IL2RA	-0.02	0.12	-10000	0	-0.38	87	87
IL2RB	0.001	0.066	-10000	0	-0.31	42	42
TERT	-0.044	0.1	-10000	0	-0.29	165	165
E2F1	0.02	0.068	-10000	0	-0.44	23	23
SOS1	0.011	0.003	-10000	0	-10000	0	0
RPS6	0	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.005	0.03	23	-10000	0	23
PTPN11	0.011	0.003	-10000	0	-10000	0	0
IL2RG	-0.004	0.087	-10000	0	-0.36	53	53
actin cytoskeleton organization	0.058	0.087	-10000	0	-0.5	11	11
GRB2	0.011	0.01	-10000	0	-0.29	1	1
IL2	0.006	0.026	-10000	0	-0.29	8	8
PIK3CA	0.013	0.01	-10000	0	-0.29	1	1
Rac1/GTP	0.025	0.055	-10000	0	-0.45	14	14
LCK	-0.007	0.1	-10000	0	-0.41	53	53
BCL2	0.039	0.2	-10000	0	-0.86	43	43

×

E-cadherin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.014	0.083	-9999	-0.52	29	29
E-cadherin/beta catenin	-0.015	0.095	-9999	-0.6	28	28
CTNNB1	0	0	-9999	-10000	0	0
JUP	-0.001	0.025	-9999	-0.54	2	2
CDH1	-0.02	0.12	-9999	-0.79	28	28

×

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	-0.017	0.082	-9999	-0.51	23	23
MAP4K1	-0.015	0.07	-9999	-0.31	53	53
MAP3K8	-0.007	0.072	-9999	-0.74	10	10
PRKCB	-0.019	0.11	-9999	-0.55	39	39
DBNL	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
MAP3K1	0.036	0.053	-9999	-0.47	4	4
JUN	0.016	0.12	-9999	-0.6	35	35
MAP3K7	0.036	0.052	-9999	-0.48	3	3
GRAP2	-0.014	0.1	-9999	-0.72	21	21
CRK	0	0	-9999	-10000	0	0
MAP2K4	0.043	0.056	-9999	-0.46	5	5
LAT	-0.005	0.048	-9999	-0.35	17	17
LCP2	0	0.009	-9999	-0.29	1	1
MAPK8	0.012	0.12	-9999	-0.68	28	28
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.008	0.048	-9999	-0.35	18	18
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.016	0.077	-9999	-0.48	23	23

×

IL1-mediated signaling events

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
UBC13/UEV1A	0	0.008	-10000	0	-10000	0	0
PRKCZ	-0.001	0.024	-10000	0	-0.79	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	-0.007	0.042	-10000	0	-0.44	5	5
IRAK/TOLLIP	-0.001	0.01	-10000	0	-10000	0	0
IKBKB	-0.001	0.013	-10000	0	-0.29	2	2
IKBKG	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.031	0.12	-10000	0	-0.58	43	43
IL1A	-0.005	0.039	-10000	0	-0.29	20	20
IL1B	0.011	0.092	-10000	0	-0.69	17	17
IRAK/TRAF6/p62/Atypical PKCs	-0.001	0.014	-10000	0	-0.39	1	1
IL1R2	-0.037	0.15	-10000	0	-0.57	71	71
IL1R1	-0.017	0.12	-10000	0	-0.79	24	24
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.002	0.063	0.23	33	-0.32	19	52
TOLLIP	0	0.009	-10000	0	-0.29	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	0.08	-10000	0	-0.37	40	40
MAP3K7	0	0.009	-10000	0	-0.29	1	1
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.023	0.11	-10000	0	-0.49	51	51
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.013	0.075	-10000	0	-0.49	25	25
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.012	0.07	-10000	0	-0.45	25	25
IL1 beta fragment/IL1R1/IL1RAP	-0.02	0.11	-10000	0	-0.53	40	40
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	0.027	0.075	-10000	0	-0.39	34	34
IRAK1	0.021	0.013	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.021	0.097	-10000	0	-0.6	26	26
IRAK4	0	0	-10000	0	-10000	0	0
PRKCI	0	0.009	-10000	0	-0.29	1	1
TRAF6	0	0	-10000	0	-10000	0	0
PI3K	-0.008	0.068	-10000	0	-0.6	14	14
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.012	0.063	-10000	0	-0.35	26	26
CHUK	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.02	0.11	-10000	0	-0.53	40	40
IL1 beta/IL1R2	-0.033	0.13	-10000	0	-0.55	56	56
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.008	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.021	0.099	-10000	0	-0.84	7	7
IRAK3	-0.031	0.15	-10000	0	-0.78	44	44
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.018	0.097	-10000	0	-0.48	40	40
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.008	0.051	-10000	0	-0.33	25	25
IL1 alpha/IL1R1/IL1RAP	-0.015	0.083	-10000	0	-0.54	25	25
RELA	0	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0	0.009	-10000	0	-0.29	1	1
MYD88	0	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	-0.001	0.008	-10000	0	-10000	0	0
IL1RAP	-0.001	0.034	-10000	0	-0.79	2	2
UBE2N	0	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.015	0.078	-10000	0	-0.81	4	4
CASP1	-0.004	0.053	-10000	0	-0.79	5	5
IL1RN/IL1R2	-0.035	0.12	-10000	0	-0.57	47	47
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.019	0.1	-10000	0	-0.5	40	40
TMEM189-UBE2V1	-0.001	0.013	-10000	0	-0.29	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.009	0.057	-10000	0	-0.38	24	24
PIK3CA	0	0.009	-10000	0	-0.29	1	1
IL1RN	-0.012	0.064	-10000	0	-0.32	41	41
TRAF6/TAK1/TAB1/TAB2	0	0.006	-10000	0	-10000	0	0
MAP2K6	-0.01	0.062	-10000	0	-0.41	25	25

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.003	0.048	-9999	-0.79	4	4
mol:S1P	0.001	0.004	-9999	-10000	0	0
S1P1/S1P/Gi	-0.03	0.095	-9999	-0.33	95	95
GNAO1	-0.018	0.13	-9999	-0.48	67	67
S1P/S1P3/G12/G13	-0.001	0.013	-9999	-10000	0	0
AKT1	-0.011	0.051	-9999	-0.68	4	4
AKT3	0.012	0.2	-9999	-1.4	20	20
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.003	0.047	-9999	-0.79	4	4
GNAI2	0.013	0.003	-9999	-10000	0	0
GNAI3	0.012	0.002	-9999	-10000	0	0
GNAI1	-0.033	0.19	-9999	-0.79	62	62
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.01	0.029	-9999	-0.3	10	10
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.009	0.11	-9999	-0.39	40	40
MAPK3	0.017	0.1	-9999	-0.51	14	14
MAPK1	0.017	0.1	-9999	-0.51	14	14
JAK2	0.019	0.1	-9999	-0.45	20	20
CXCR4	0.014	0.1	-9999	-0.48	19	19
FLT1	0.013	0.025	-9999	-0.8	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.017	0.1	-9999	-0.51	14	14
S1P/S1P3/Gi	0.009	0.11	-9999	-0.39	40	40
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.026	0.084	-9999	-0.49	14	14
VEGFA	0.01	0.032	-9999	-0.3	12	12
S1P/S1P2/Gi	0.008	0.1	-9999	-0.37	39	39
VEGFR1 homodimer/VEGFA homodimer	0.021	0.03	-9999	-0.62	1	1
RHOA	0	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.007	0.043	-9999	-0.34	18	18
GNAQ	-0.002	0.041	-9999	-0.79	3	3
GNAZ	0.005	0.076	-9999	-0.79	10	10
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.013	0.084	-9999	-0.46	30	30
GNA15	-0.003	0.033	-9999	-0.36	8	8
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	-0.003	0.048	-9999	-0.79	4	4
Rac1/GTP	-0.026	0.084	-9999	-0.49	14	14

×

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	-0.007	0.052	-9999	-0.34	23	23
GNAI2	0	0	-9999	-10000	0	0
mol:S1P	0.02	0.019	-9999	-0.36	2	2
GNAO1	-0.03	0.13	-9999	-0.48	67	67
mol:Sphinganine-1-P	0.017	0.039	-9999	-0.6	2	2
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.001	0.011	-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	-0.29	10	10
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.001	0.014	-9999	-0.31	2	2
S1PR5	-0.008	0.058	-9999	-0.35	25	25
S1PR4	-0.014	0.079	-9999	-0.36	44	44
GNAI1	-0.045	0.18	-9999	-0.79	62	62
S1P/S1P5/G12	-0.005	0.032	-9999	-0.38	5	5
S1P/S1P3/Gq	-0.005	0.038	-9999	-0.29	18	18
S1P/S1P4/Gi	-0.028	0.084	-9999	-0.33	42	42
GNAQ	-0.002	0.041	-9999	-0.79	3	3
GNAZ	-0.007	0.075	-9999	-0.79	10	10
GNA14	-0.013	0.084	-9999	-0.46	30	30
GNA15	-0.003	0.033	-9999	-0.36	8	8
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	-0.003	0.048	-9999	-0.79	4	4
ABCC1	0	0	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.016	0.092	-9999	-0.58	28	28
KLHL20	-0.008	0.031	-9999	-0.24	3	3
CYFIP2	-0.01	0.065	-9999	-0.36	31	31
Rac1/GDP	0.05	0.065	-9999	-0.34	28	28
ENAH	-0.015	0.091	-9999	-0.57	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	-0.008	0.045	-9999	-0.49	1	1
ABI1/Sra1/Nap1	-0.006	0.023	-9999	-0.19	4	4
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.016	0.078	-9999	-0.47	30	30
RAPGEF1	0.04	0.085	-9999	-0.48	28	28
CTNND1	0	0.009	-9999	-0.29	1	1
regulation of calcium-dependent cell-cell adhesion	-0.016	0.095	-9999	-0.6	28	28
CRK	0.032	0.092	-9999	-0.53	28	28
E-cadherin/gamma catenin/alpha catenin	-0.014	0.083	-9999	-0.52	29	29
alphaE/beta7 Integrin	-0.006	0.04	-9999	-0.6	2	2
IQGAP1	0	0	-9999	-10000	0	0
NCKAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.003	0.035	-9999	-0.48	6	6
DLG1	-0.015	0.091	-9999	-0.57	28	28
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.008	0.039	-9999	-0.31	2	2
MLLT4	-0.005	0.059	-9999	-0.72	7	7
ARF6/GTP/NME1/Tiam1	-0.007	0.029	-9999	-10000	0	0
PI3K	-0.01	0.051	-9999	-0.42	2	2
ARF6	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.016	0.097	-9999	-0.6	29	29
TIAM1	-0.001	0.018	-9999	-0.29	4	4
E-cadherin(dimer)/Ca2+	-0.011	0.07	-9999	-0.44	28	28
AKT1	-0.006	0.028	-9999	-0.24	1	1
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
CDH1	-0.02	0.12	-9999	-0.79	28	28
RhoA/GDP	0.05	0.065	-9999	-0.43	2	2
actin cytoskeleton organization	-0.006	0.023	-9999	-0.17	3	3
CDC42/GDP	0.05	0.065	-9999	-0.34	28	28
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.009	0.054	-9999	-0.33	29	29
ITGB7	-0.009	0.058	-9999	-0.32	32	32
RAC1	0	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.012	0.074	-9999	-0.47	28	28
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.012	0.071	-9999	-0.45	28	28
mol:GDP	0.047	0.075	-9999	-0.41	28	28
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	-0.001	0.025	-9999	-0.54	2	2
p120 catenin/RhoA/GDP	-0.009	0.056	-9999	-0.54	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	0.029	-9999	-0.22	7	7
NME1	-0.015	0.065	-9999	-0.29	56	56
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.015	0.092	-9999	-0.57	29	29
regulation of cell-cell adhesion	-0.007	0.04	-9999	-0.42	1	1
WASF2	-0.003	0.012	-9999	-10000	0	0
Rap1/GTP	-0.009	0.053	-9999	-0.58	1	1
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.015	0.074	-9999	-0.44	31	31
CCND1	-0.009	0.035	-9999	-0.27	7	7
VAV2	0.036	0.089	-9999	-0.51	28	28
RAP1/GDP	-0.009	0.053	-9999	-0.56	1	1
adherens junction assembly	-0.015	0.088	-9999	-0.55	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	-0.014	0.07	-9999	-0.41	31	31
E-cadherin/beta catenin	-0.012	0.077	-9999	-0.49	28	28
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.015	0.091	-9999	-0.57	28	28
PIK3CA	0	0.009	-9999	-0.29	1	1
Rac1/GTP	-0.01	0.051	-9999	-0.35	6	6
E-cadherin/beta catenin/alpha catenin	-0.013	0.082	-9999	-0.52	28	28
ITGAE	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.016	0.097	-9999	-0.61	28	28

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.019	0.082	0.33	1	-0.36	58	59
FRAP1	0.01	0.023	-10000	0	-10000	0	0
AKT1	-0.017	0.071	0.24	1	-0.31	58	59
INSR	0	0.009	-10000	0	-0.29	1	1
Insulin Receptor/Insulin	0	0.005	-10000	0	-10000	0	0
mol:GTP	-0.013	0.055	-10000	0	-0.33	15	15
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.004	0.018	-10000	0	-10000	0	0
TSC2	0	0.002	-10000	0	-10000	0	0
RHEB/GDP	-0.011	0.048	-10000	0	-0.34	1	1
TSC1	0	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.017	0.082	-10000	0	-0.42	45	45
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.005	0.021	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.018	0.045	-10000	0	-0.25	15	15
MAP3K5	0.009	0.027	-10000	0	-0.44	4	4
PIK3R1	-0.01	0.089	-10000	0	-0.79	14	14
apoptosis	0.009	0.027	-10000	0	-0.44	4	4
mol:LY294002	0	0	-10000	0	-0.002	45	45
EIF4B	0.024	0.041	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.007	0.03	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	-0.001	0.008	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.021	0.087	-10000	0	-0.38	59	59
mTOR/RHEB/GTP/Raptor/GBL	0.025	0.033	0.18	1	-10000	0	1
FKBP1A	0	0.009	-10000	0	-0.29	1	1
RHEB/GTP	-0.011	0.047	-10000	0	-0.34	1	1
mol:Amino Acids	0	0	-10000	0	-0.002	45	45
FKBP12/Rapamycin	0	0.006	-10000	0	-0.2	1	1
PDPK1	-0.017	0.074	0.26	1	-0.33	58	59
EIF4E	0	0	-10000	0	-10000	0	0
ASK1/PP5C	-0.004	0.039	-10000	0	-0.62	4	4
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.016	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.014	0.059	-10000	0	-0.35	15	15
tumor necrosis factor receptor activity	0	0	0.002	45	-10000	0	45
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	-0.011	0.09	-10000	0	-0.45	45	45
INS	0	0	-10000	0	-10000	0	0
PTEN	-0.001	0.034	-10000	0	-0.79	2	2
PDK2	-0.019	0.079	0.26	1	-0.34	61	62
EIF4EBP1	0.013	0.01	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.29	1	1
PPP2R5D	0.017	0.021	-10000	0	-10000	0	0
peptide biosynthetic process	0.016	0.005	-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	14	16
EEF2	0.016	0.005	-10000	0	-10000	0	0
eIF4E/4E-BP1	0	0	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	-0.004	0.024	-9999	-0.4	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	0.028	-9999	-0.29	10	10
alpha4/beta7 Integrin/MAdCAM1	-0.01	0.043	-9999	-0.45	3	3
EPO	-0.047	0.11	-9999	-0.29	177	177
alpha4/beta7 Integrin	-0.008	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	0.069	-9999	-10000	0	0
lamellipodium assembly	-0.004	0.046	-9999	-0.4	14	14
PIK3CA	0	0.009	-9999	-0.29	1	1
PI3K	-0.008	0.068	-9999	-0.6	14	14
ARF6	0	0	-9999	-10000	0	0
JAK2	-0.01	0.025	-9999	-0.5	1	1
PXN	0	0	-9999	-10000	0	0
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
MADCAM1	-0.012	0.057	-9999	-0.29	43	43
cell adhesion	-0.01	0.043	-9999	-0.45	3	3
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
SRC	0.025	0.057	-9999	-0.47	13	13
ITGB7	-0.009	0.058	-9999	-0.32	32	32
RAC1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.008	0.058	-9999	-0.52	13	13
p130Cas/Crk/Dock1	-0.006	0.042	-9999	-0.38	13	13
VCAM1	-0.011	0.088	-9999	-0.63	19	19
RHOA	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.002	0.014	-9999	-10000	0	0
BCAR1	0.034	0.054	-9999	-0.43	13	13
EPOR	0	0.009	-9999	-0.29	1	1
mol:GDP	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
GIT1	-0.001	0.02	-9999	-0.29	5	5
Rac1/GTP	-0.005	0.047	-9999	-0.41	14	14

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.002	0.028	-10000	0	-0.46	4	4
TRAF2/ASK1	-0.002	0.033	-10000	0	-0.52	4	4
ATM	0	0	-10000	0	-10000	0	0
MAP2K3	0.025	0.045	-10000	0	-0.44	2	2
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.025	0.064	-10000	0	-0.43	6	6
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.038	0.098	-10000	0	-0.29	141	141
TXN	0.008	0.006	-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	-0.001	0.024	-10000	0	-0.79	1	1
MAP3K6	-0.001	0.024	-10000	0	-0.79	1	1
MAP3K7	0	0.009	-10000	0	-0.29	1	1
MAP3K4	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.003	0.04	-10000	0	-0.6	5	5
TAK1/TAB family	0.001	0.011	0.21	3	-10000	0	3
RAC1/OSM/MEKK3	0	0.005	-10000	0	-10000	0	0
TRAF2	-0.001	0.018	-10000	0	-0.29	4	4
RAC1/OSM/MEKK3/MKK3	-0.006	0.023	-10000	0	-0.4	1	1
TRAF6	0.008	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.066	0.2	-10000	0	-0.59	123	123
CCM2	-0.001	0.013	-10000	0	-0.29	2	2
CaM/Ca2+/CAMKIIB	-0.042	0.13	-10000	0	-0.52	74	74
MAPK11	-0.002	0.041	-10000	0	-0.79	3	3
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.04	0.12	-10000	0	-0.48	77	77
OSM/MEKK3	0	0.008	-10000	0	-10000	0	0
TAOK1	-0.006	0.099	-10000	0	-0.44	55	55
TAOK2	0.017	0	-10000	0	-10000	0	0
TAOK3	0.017	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	-0.003	0.048	-10000	0	-0.79	4	4
MAP3K10	0	0.009	-10000	0	-0.29	1	1
MAP3K3	0	0	-10000	0	-10000	0	0
TRX/ASK1	-0.002	0.031	-10000	0	-0.52	4	4
GADD45/MTK1/MTK1	-0.014	0.037	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0	0	-10000	0	-10000	0	0
NFATC1	0.049	0.029	-10000	0	-0.39	1	1
NFATC2	0.015	0.064	-10000	0	-0.31	11	11
NFATC3	0	0.015	-10000	0	-0.51	1	1
YWHAE	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.012	0.094	-10000	0	-0.39	38	38
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	-0.019	0.075	-10000	0	-0.49	17	17
BCL2/BAX	-0.021	0.11	-10000	0	-0.61	37	37
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	0.018	-10000	0	-0.29	4	4
MAPK14	0.01	0.003	-10000	0	-10000	0	0
BAD	0	0.009	-10000	0	-0.29	1	1
CABIN1/MEF2D	-0.02	0.08	-10000	0	-0.52	17	17
Calcineurin A alpha-beta B1/BCL2	-0.027	0.14	-10000	0	-0.79	37	37
FKBP8	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.019	0.079	0.51	17	-10000	0	17
KPNB1	0	0	-10000	0	-10000	0	0
KPNA2	-0.029	0.087	-10000	0	-0.29	108	108
XPO1	0	0	-10000	0	-10000	0	0
SFN	-0.016	0.099	-10000	0	-0.5	36	36
MAP3K8	0.004	0.073	-10000	0	-0.74	10	10
NFAT4/CK1 alpha	-0.001	0.016	-10000	0	-0.43	1	1
MEF2D/NFAT1/Cbp/p300	-0.038	0.093	-10000	0	-0.46	3	3
CABIN1	0.012	0.095	-10000	0	-0.39	38	38
CALM1	0.001	0.003	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
MAP3K1	-0.001	0.024	-10000	0	-0.79	1	1
CAMK4	-0.011	0.059	-10000	0	-0.79	1	1
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	0.044	-10000	0	-0.6	1	1
YWHAB	0	0	-10000	0	-10000	0	0
MAPK8	0.004	0.072	-10000	0	-0.79	9	9
MAPK9	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0	0.009	-10000	0	-0.29	1	1
NFAT1-c-4/YWHAQ	-0.002	0.021	-10000	0	-0.4	1	1
PRKCH	-0.001	0.024	-10000	0	-0.79	1	1
CABIN1/Cbp/p300	-0.001	0.003	-10000	0	-10000	0	0
CASP3	0.01	0.003	-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	0.035	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.003	0.024	-10000	0	-10000	0	0
PRKCB	-0.019	0.11	-10000	0	-0.55	39	39
PRKCE	0	0	-10000	0	-10000	0	0
JNK2/NFAT4	0	0.014	-10000	0	-0.46	1	1
BAD/BCL-XL	0	0.006	-10000	0	-10000	0	0
PRKCD	0	0.009	-10000	0	-0.29	1	1
NUP214	0	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.024	-10000	0	-0.79	1	1
PRKCA	-0.021	0.13	-10000	0	-0.76	31	31
PRKCG	-0.013	0.061	-10000	0	-0.29	49	49
PRKCQ	-0.036	0.16	-10000	0	-0.68	57	57
FKBP38/BCL2	-0.02	0.11	-10000	0	-0.6	37	37
EP300	0	0.001	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
NFATc/JNK1	0.047	0.049	-10000	0	-0.37	10	10
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0.006	-10000	0	-0.2	1	1
CSNK1A1	0.018	0.006	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.006	0.032	-10000	0	-0.52	1	1
NFATc/ERK1	0.053	0.027	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.019	0.075	-10000	0	-0.48	17	17
NR4A1	-0.014	0.22	-10000	0	-0.7	99	99
GSK3B	0.011	0.003	-10000	0	-10000	0	0
positive T cell selection	0	0.015	-10000	0	-0.5	1	1
NFAT1/CK1 alpha	-0.016	0.039	-10000	0	-0.29	3	3
RCH1/ KPNB1	-0.018	0.056	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
PRKACA	0.01	0.003	-10000	0	-10000	0	0
AKAP5	-0.015	0.067	-10000	0	-0.3	54	54
MEF2D	0	0.001	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	-0.001	0.015	-10000	0	-0.29	3	3
NFATc/p38 alpha	0.051	0.031	-10000	0	-0.36	1	1
CREBBP	0	0.001	-10000	0	-10000	0	0
BCL2	-0.027	0.14	-10000	0	-0.79	37	37

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	-0.006	0.054	-10000	0	-0.47	15	15
HDAC3	0	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.012	-10000	0	-0.39	1	1
GATA1/HDAC4	-0.004	0.03	-10000	0	-0.6	1	1
GATA1/HDAC5	-0.003	0.024	-10000	0	-10000	0	0
GATA2/HDAC5	-0.018	0.097	-10000	0	-0.6	28	28
HDAC5/BCL6/BCoR	-0.004	0.044	-10000	0	-0.52	8	8
HDAC9	-0.01	0.081	-10000	0	-0.52	22	22
Glucocorticoid receptor/Hsp90/HDAC6	-0.008	0.062	-10000	0	-0.52	16	16
HDAC4/ANKRA2	-0.001	0.018	-10000	0	-0.6	1	1
HDAC5/YWHAB	0	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0.001	-10000	0	-10000	0	0
GATA2	-0.024	0.13	-10000	0	-0.63	41	41
HDAC4/RFXANK	-0.002	0.023	-10000	0	-0.6	1	1
BCOR	-0.001	0.034	-10000	0	-0.79	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	-0.001	0.013	-10000	0	-0.29	2	2
HDAC5	0	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.008	0.07	-10000	0	-0.6	15	15
Histones	-0.003	0.026	-10000	0	-10000	0	0
ADRBK1	0	0	-10000	0	-10000	0	0
HDAC4	-0.001	0.024	-10000	0	-0.79	1	1
XPO1	0	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0	0	-10000	0	-10000	0	0
HDAC4/Ubc9	-0.001	0.018	-10000	0	-0.6	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	-0.001	0.014	-10000	0	-10000	0	0
CAMK4	-0.011	0.059	-10000	0	-0.79	1	1
Tubulin/HDAC6	-0.001	0.017	-10000	0	-0.52	1	1
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	-0.005	0.037	-10000	0	-0.29	18	18
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
NR3C1	-0.012	0.095	-10000	0	-0.79	16	16
SUMO1/HDAC4	0	0.013	-10000	0	-0.43	1	1
SRF	0	0	-10000	0	-10000	0	0
HDAC4/YWHAB	-0.001	0.018	-10000	0	-0.6	1	1
Tubulin	-0.001	0.02	-10000	0	-0.6	1	1
HDAC4/14-3-3 E	-0.001	0.018	-10000	0	-0.6	1	1
GNB1	0	0	-10000	0	-10000	0	0
RANGAP1	0	0.009	-10000	0	-0.29	1	1
BCL6/BCoR	-0.004	0.051	-10000	0	-0.6	8	8
HDAC4/HDAC3/SMRT (N-CoR2)	0	0.016	-10000	0	-0.52	1	1
HDAC4/SRF	-0.006	0.034	-10000	0	-0.52	2	2
HDAC4/ER alpha	-0.11	0.21	-10000	0	-0.6	166	166
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.025	-10000	0	-10000	0	0
cell motility	-0.001	0.017	-10000	0	-0.51	1	1
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	-0.004	0.058	-10000	0	-0.79	6	6
HDAC4/CaMK II delta B	-0.001	0.024	-10000	0	-0.79	1	1
Hsp90/HDAC6	0	0.006	-10000	0	-10000	0	0
ESR1	-0.15	0.28	-10000	0	-0.58	288	288
HDAC6/HDAC11	-0.001	0.011	-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	0.034	-10000	0	-0.79	2	2
RAN	0	0	-10000	0	-10000	0	0
HDAC4/MEF2C	-0.001	0.023	-10000	0	-0.44	3	3
GNG2	-0.011	0.092	-10000	0	-0.79	15	15
NCOR2	0	0	-10000	0	-10000	0	0
TUBB2A	-0.001	0.027	-10000	0	-0.46	3	3
HDAC11	-0.001	0.018	-10000	0	-0.29	4	4
HSP90AA1	0	0.009	-10000	0	-0.29	1	1
RANBP2	0	0	-10000	0	-10000	0	0
ANKRA2	0	0	-10000	0	-10000	0	0
RFXANK	-0.002	0.022	-10000	0	-0.29	6	6
nuclear import	0	0.013	0.43	1	-10000	0	1

×

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	-0.009	0.058	-9999	-0.32	32	32
ITGA4	-0.003	0.028	-9999	-0.29	10	10
alpha4/beta7 Integrin	-0.008	0.046	-9999	-0.44	6	6
alpha4/beta1 Integrin	-0.002	0.018	-9999	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.021	0.11	-9999	-0.6	37	37
AKT1	0.079	0.073	-9999	-0.68	7	7
PTK2B	0.035	0.12	-9999	-1	8	8
VEGFR2 homodimer/Frs2	-0.009	0.083	-9999	-0.81	10	10
CAV1	-0.17	0.33	-9999	-0.79	241	241
CALM1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.009	0.077	-9999	-0.74	10	10
endothelial cell proliferation	0.082	0.087	-9999	-0.69	7	7
mol:Ca2+	0.05	0.074	-9999	-0.84	6	6
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.007	0.073	-9999	-0.9	6	6
RP11-342D11.1	0.042	0.074	-9999	-0.85	6	6
CDH5	-0.007	0.075	-9999	-0.79	10	10
VEGFA homodimer	-0.001	0.012	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
SHC2	-0.02	0.12	-9999	-0.77	28	28
HRAS/GDP	-0.006	0.06	-9999	-0.75	6	6
SH2D2A	-0.035	0.1	-9999	-0.3	125	125
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.003	0.055	-9999	-0.67	6	6
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.021	0.087	-9999	-0.7	13	13
VEGFR1 homodimer	-0.001	0.024	-9999	-0.79	1	1
SHC/GRB2/SOS1	-0.005	0.066	-9999	-0.82	6	6
GRB10	0.05	0.074	-9999	-0.84	6	6
PTPN11	0	0	-9999	-10000	0	0
GRB2	0	0.009	-9999	-0.29	1	1
PAK1	-0.007	0.044	-9999	-0.29	25	25
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.009	0.095	-9999	-1	8	8
HRAS	-0.003	0.028	-9999	-0.29	10	10
VEGF/Rho/ROCK1/Integrin Complex	-0.011	0.065	-9999	-0.59	8	8
HIF1A	0	0	-9999	-10000	0	0
FRS2	-0.003	0.029	-9999	-0.29	11	11
oxygen and reactive oxygen species metabolic process	-0.007	0.071	-9999	-0.88	6	6
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.002	0.041	-9999	-0.79	3	3
Nck/Pak	-0.004	0.028	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.009	0.084	-9999	-0.77	11	11
mol:GDP	-0.005	0.062	-9999	-0.78	6	6
mol:NADP	0.073	0.053	-9999	-0.55	6	6
eNOS/Hsp90	0.074	0.049	-9999	-0.51	6	6
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
mol:IP3	0.05	0.076	-9999	-0.86	6	6
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	-0.001	0.025	-9999	-0.54	2	2
VEGFA	-0.003	0.03	-9999	-10000	0	0
VEGFC	0	0	-9999	-10000	0	0
FAK1/Vinculin	0.056	0.1	-9999	-0.96	7	7
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.022	0.12	-9999	-1.1	8	8
PTPN6	-0.001	0.013	-9999	-0.29	2	2
EPAS1	-0.006	0.071	-9999	-0.69	10	10
mol:L-citrulline	0.073	0.053	-9999	-0.55	6	6
ITGAV	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.008	0.073	-9999	-0.9	6	6
VEGFR2 homodimer/VEGFA homodimer	-0.008	0.076	-9999	-0.94	6	6
VEGFR2/3 heterodimer	-0.009	0.092	-9999	-0.86	11	11
VEGFB	0	0	-9999	-10000	0	0
MAPK11	0.054	0.08	-9999	-0.9	6	6
VEGFR2 homodimer	0.027	0.094	-9999	-0.9	10	10
FLT1	-0.001	0.024	-9999	-0.79	1	1
NEDD4	0	0	-9999	-10000	0	0
MAPK3	0.05	0.084	-9999	-0.83	7	7
MAPK1	0.05	0.084	-9999	-0.83	7	7
VEGFA145/NRP2	-0.004	0.039	-9999	-0.65	3	3
VEGFR1/2 heterodimer	-0.008	0.087	-9999	-0.85	10	10
KDR	0.027	0.094	-9999	-0.91	10	10
VEGFA165/NRP1/VEGFR2 homodimer	-0.006	0.082	-9999	-0.93	7	7
SRC	0	0.009	-9999	-0.29	1	1
platelet activating factor biosynthetic process	0.052	0.085	-9999	-0.86	7	7
PI3K	-0.009	0.079	-9999	-0.9	7	7
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.008	0.077	-9999	-0.74	10	10
FES	0.049	0.081	-9999	-0.88	6	6
GAB1	-0.006	0.071	-9999	-0.9	6	6
VEGFR2 homodimer/VEGFA homodimer/Src	-0.008	0.077	-9999	-0.74	10	10
CTNNB1	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.01	0.17	-9999	-0.7	9	9
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.008	0.078	-9999	-0.88	7	7
PI3K/GAB1	0.078	0.081	-9999	-0.72	7	7
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.003	0.071	-9999	-0.87	6	6
PRKACA	0	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.008	0.086	-9999	-0.8	11	11
HSP90AA1	0	0.009	-9999	-0.29	1	1
CDC42	0.05	0.077	-9999	-0.88	6	6
actin cytoskeleton reorganization	-0.021	0.086	-9999	-0.69	13	13
PTK2	0.051	0.11	-9999	-1.1	7	7
EDG1	0.042	0.074	-9999	-0.85	6	6
mol:DAG	0.05	0.076	-9999	-0.86	6	6
CaM/Ca2+	-0.006	0.063	-9999	-0.79	6	6
MAP2K3	0.055	0.079	-9999	-0.83	6	6
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.005	0.072	-9999	-0.9	6	6
PLCG1	0.05	0.077	-9999	-0.88	6	6
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.008	0.074	-9999	-0.9	6	6
IQGAP1	0	0	-9999	-10000	0	0
YES1	-0.001	0.024	-9999	-0.79	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.008	0.077	-9999	-0.74	10	10
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.008	0.077	-9999	-0.74	10	10
cell migration	0.078	0.091	-9999	-0.79	7	7
mol:PI-3-4-5-P3	-0.008	0.07	-9999	-0.79	7	7
FYN	-0.001	0.034	-9999	-0.79	2	2
VEGFB/NRP1	-0.007	0.064	-9999	-0.8	6	6
mol:NO	0.073	0.053	-9999	-0.55	6	6
PXN	0	0	-9999	-10000	0	0
HRAS/GTP	-0.006	0.06	-9999	-0.75	6	6
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.005	0.073	-9999	-0.9	6	6
VHL	0	0	-9999	-10000	0	0
ITGB3	-0.028	0.14	-9999	-0.79	37	37
NOS3	0.075	0.059	-9999	-0.63	6	6
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.019	0.1	-9999	-0.54	37	37
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.045	0.11	-9999	-0.99	6	6
PRKCB	0.046	0.1	-9999	-0.86	8	8
VCL	0	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.007	0.069	-9999	-0.86	6	6
VEGFR1/2 heterodimer/VEGFA homodimer	-0.008	0.082	-9999	-0.79	10	10
VEGFA165/NRP2	-0.004	0.039	-9999	-0.65	3	3
MAPKKK cascade	-0.004	0.06	-9999	-0.75	6	6
NRP2	-0.002	0.042	-9999	-0.66	4	4
VEGFC homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
ROCK1	-0.001	0.024	-9999	-0.79	1	1
FAK1/Paxillin	0.056	0.1	-9999	-0.96	7	7
MAP3K13	0.048	0.083	-9999	-0.88	6	6
PDPK1	0.073	0.07	-9999	-0.67	7	7

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	-0.001	0.027	-9999	-0.89	1	1
VEGFR1 homodimer/NRP1	-0.001	0.027	-9999	-0.9	1	1
mol:DAG	0.038	0.032	-9999	-0.64	2	2
VEGFR1 homodimer/NRP1/VEGFR 121	-0.002	0.028	-9999	-0.84	1	1
CaM/Ca2+	-0.002	0.027	-9999	-0.6	2	2
HIF1A	0	0.011	-9999	-0.38	1	1
GAB1	0	0	-9999	-10000	0	0
AKT1	-0.006	0.052	-9999	-0.71	1	1
PLCG1	0.038	0.032	-9999	-0.64	2	2
NOS3	0.061	0.033	-9999	-0.7	1	1
CBL	0	0	-9999	-10000	0	0
mol:NO	0.06	0.032	-9999	-0.53	2	2
FLT1	0.029	0.031	-9999	-1	1	1
PGF	-0.002	0.031	-9999	-0.38	6	6
VEGFR1 homodimer/NRP2/VEGFR121	-0.003	0.046	-9999	-0.78	3	3
CALM1	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.29	1	1
eNOS/Hsp90	0.065	0.031	-9999	-0.64	1	1
endothelial cell proliferation	0.036	0.089	-9999	-0.56	8	8
mol:Ca2+	0.038	0.031	-9999	-0.63	2	2
MAPK3	0.039	0.082	-9999	-0.43	30	30
MAPK1	0.039	0.082	-9999	-0.43	30	30
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
PLGF homodimer	-0.002	0.031	-9999	-0.38	6	6
PRKACA	0	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.17	0.33	-9999	-0.79	241	241
VEGFA homodimer	-0.003	0.03	-9999	-0.29	12	12
VEGFR1 homodimer/VEGFA homodimer	-0.002	0.031	-9999	-0.89	1	1
platelet activating factor biosynthetic process	0.046	0.079	-9999	-1.1	1	1
PI3K	-0.007	0.056	-9999	-0.45	16	16
PRKCA	0.032	0.086	-9999	-0.46	30	30
PRKCB	0.034	0.077	-9999	-0.47	21	21
VEGFR1 homodimer/PLGF homodimer	-0.002	0.032	-9999	-0.7	2	2
VEGFA	-0.003	0.031	-9999	-0.29	12	12
VEGFB	0	0	-9999	-10000	0	0
mol:IP3	0.038	0.032	-9999	-0.64	2	2
RASA1	0.039	0.026	-9999	-0.83	1	1
NRP2	-0.002	0.042	-9999	-0.66	4	4
VEGFR1 homodimer	0.029	0.031	-9999	-1	1	1
VEGFB homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.03	0.18	-9999	-0.58	9	9
PTPN11	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.007	0.055	-9999	-0.45	16	16
mol:L-citrulline	0.06	0.032	-9999	-0.53	2	2
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.002	0.027	-9999	-0.79	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.002	0.028	-9999	-0.83	1	1
CD2AP	0	0.009	-9999	-0.29	1	1
PI3K/GAB1	-0.007	0.053	-9999	-0.43	15	15
PDPK1	-0.007	0.052	-9999	-0.42	16	16
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.002	0.028	-9999	-0.83	1	1
mol:NADP	0.06	0.032	-9999	-0.53	2	2
HSP90AA1	0	0.009	-9999	-0.29	1	1
ubiquitin-dependent protein catabolic process	-0.002	0.026	-9999	-0.78	1	1
VEGFR1 homodimer/NRP2	-0.002	0.046	-9999	-0.78	3	3

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.01	0.035	-9999	-0.41	2	2
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	-0.007	0.028	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0.022	-9999	-0.52	2	2
antigen processing and presentation of peptide antigen via MHC class I	-0.006	0.039	-9999	-0.33	2	2
CaM/Ca2+	0.009	0.031	-9999	-0.38	2	2
RAP1A	0	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.011	0.036	-9999	-0.38	2	2
AKT1	-0.011	0.047	-9999	-0.45	2	2
MAP2K1	0.04	0.044	-9999	-0.39	1	1
MAP3K11	0.03	0.043	-9999	-0.38	2	2
IFNGR1	0.012	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.023	0.093	-9999	-0.41	23	23
Rap1/GTP	-0.004	0.015	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.013	0.036	-9999	-0.43	2	2
CEBPB	0.075	0.039	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.007	0.055	-9999	-1.2	1	1
STAT1	-0.011	0.036	-9999	-0.38	2	2
CALM1	0	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.03	0.1	-9999	-0.28	150	150
PIK3CA	0	0.009	-9999	-0.29	1	1
STAT1 (dimer)/PIAS1	-0.01	0.032	-9999	-0.36	2	2
CEBPB/PTGES2/Cbp/p300	-0.001	0.012	-9999	-10000	0	0
mol:Ca2+	0.008	0.034	-9999	-0.41	2	2
MAPK3	0.054	0.04	-9999	-10000	0	0
STAT1 (dimer)	-0.006	0.054	-9999	-0.48	2	2
MAPK1	0.054	0.04	-9999	-10000	0	0
JAK2	0.011	0.024	-9999	-0.79	1	1
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
JAK1	0.011	0.024	-9999	-0.78	1	1
CAMK2D	-0.002	0.041	-9999	-0.79	3	3
DAPK1	0.07	0.033	-9999	-10000	0	0
SMAD7	0.05	0.038	-9999	-10000	0	0
CBL/CRKL/C3G	-0.007	0.022	-9999	-10000	0	0
PI3K	0.002	0.055	-9999	-0.4	15	15
IFNG	-0.03	0.1	-9999	-0.28	150	150
apoptosis	0.053	0.029	-9999	-10000	0	0
CAMK2G	0	0	-9999	-10000	0	0
STAT3 (dimer)	0	0	-9999	-10000	0	0
CAMK2A	-0.01	0.053	-9999	-0.29	37	37
CAMK2B	-0.066	0.2	-9999	-0.59	123	123
FRAP1	0.037	0.058	-9999	-0.42	2	2
PRKCD	-0.011	0.047	-9999	-0.45	2	2
RAP1B	0	0	-9999	-10000	0	0
negative regulation of cell growth	-0.006	0.039	-9999	-0.33	2	2
PTPN2	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
IRF1	0.064	0.047	-9999	-10000	0	0
STAT1 (dimer)/PIASy	-0.01	0.033	-9999	-0.37	1	1
SOCS1	0	0.049	-9999	-1.5	1	1
mol:GDP	-0.007	0.021	-9999	-10000	0	0
CASP1	0.049	0.045	-9999	-0.35	5	5
PTGES2	0	0.009	-9999	-0.29	1	1
IRF9	0.058	0.019	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.012	0.05	-9999	-0.39	15	15
RAP1/GDP	-0.004	0.015	-9999	-10000	0	0
CBL	0.029	0.043	-9999	-0.38	2	2
MAP3K1	0.031	0.045	-9999	-0.39	3	3
PIAS1	0	0	-9999	-10000	0	0
PIAS4	0	0.002	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.006	0.039	-9999	-0.33	2	2
PTPN11	0.021	0.044	-9999	-0.41	2	2
CREBBP	0	0	-9999	-10000	0	0
RAPGEF1	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	0.017	-10000	0	-10000	0	0
oxygen homeostasis	0.012	0.012	-10000	0	-10000	0	0
TCEB2	-0.007	0.045	-10000	0	-0.29	27	27
TCEB1	-0.001	0.015	-10000	0	-0.29	3	3
VHL/Elongin B/Elongin C/HIF2A	-0.007	0.039	-10000	0	-0.4	3	3
EPO	0.14	0.15	-10000	0	-0.65	3	3
FIH (dimer)	0.023	0.012	-10000	0	-10000	0	0
APEX1	0.022	0.014	-10000	0	-0.31	1	1
SERPINE1	0.16	0.15	-10000	0	-0.66	5	5
FLT1	-0.004	0.085	-10000	0	-1.1	6	6
ADORA2A	0.14	0.16	-10000	0	-0.64	5	5
germ cell development	0.16	0.15	-10000	0	-0.65	5	5
SLC11A2	0.16	0.15	-10000	0	-0.68	4	4
BHLHE40	0.16	0.16	-10000	0	-0.8	5	5
HIF1AN	0.023	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.013	0.07	-10000	0	-0.42	5	5
ETS1	0.022	0.061	-10000	0	-0.8	6	6
CITED2	0.001	0.011	-10000	0	-10000	0	0
KDR	-0.008	0.12	-10000	0	-1.3	9	9
PGK1	0.16	0.15	-10000	0	-0.68	4	4
SIRT1	0	0	-10000	0	-10000	0	0
response to hypoxia	-0.001	0.003	-10000	0	-10000	0	0
HIF2A/ARNT	0.18	0.16	-10000	0	-0.77	5	5
EPAS1	0.091	0.083	-10000	0	-0.41	5	5
SP1	0.019	0.002	-10000	0	-10000	0	0
ABCG2	0.12	0.25	-10000	0	-0.69	80	80
EFNA1	0.16	0.15	-10000	0	-0.68	4	4
FXN	0.15	0.15	-10000	0	-0.66	4	4
POU5F1	0.16	0.15	-10000	0	-0.68	5	5
neuron apoptosis	-0.17	0.16	0.74	5	-10000	0	5
EP300	0	0	-10000	0	-10000	0	0
EGLN3	-0.001	0.085	-10000	0	-0.29	83	83
EGLN2	0.021	0.026	-10000	0	-0.28	6	6
EGLN1	0.022	0.027	-10000	0	-0.8	1	1
VHL/Elongin B/Elongin C	-0.004	0.024	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.023	0.01	-10000	0	-10000	0	0
SLC2A1	0.15	0.16	-10000	0	-0.64	6	6
TWIST1	0.13	0.21	-10000	0	-0.68	46	46
ELK1	0.019	0.009	-10000	0	-0.29	1	1
HIF2A/ARNT/Cbp/p300	0.008	0.063	-10000	0	-0.6	1	1
VEGFA	0.16	0.15	-10000	0	-0.71	4	4
CREBBP	0	0	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.002	0.028	0.3	2	-0.44	2	4
DAPP1	0.036	0.052	-10000	0	-0.58	4	4
Src family/SYK family/BLNK-LAT/BTK-ITK	0.046	0.078	-10000	0	-0.56	10	10
mol:DAG	0.052	0.05	0.21	1	-0.27	7	8
HRAS	0.009	0.029	-10000	0	-0.29	10	10
RAP1A	0	0	-10000	0	-10000	0	0
ARF5/GDP	0.038	0.032	-10000	0	-0.3	2	2
PLCG2	-0.002	0.035	-10000	0	-0.62	3	3
PLCG1	0	0	-10000	0	-10000	0	0
ARF5	0	0.009	-10000	0	-0.29	1	1
mol:GTP	-0.001	0.022	0.26	2	-0.38	2	4
ARF1/GTP	-0.001	0.023	0.28	2	-0.37	2	4
RHOA	0	0	-10000	0	-10000	0	0
YES1	-0.001	0.024	-10000	0	-0.79	1	1
RAP1A/GTP	-0.001	0.022	0.25	2	-0.38	2	4
ADAP1	-0.003	0.032	0.26	2	-0.39	5	7
ARAP3	-0.001	0.022	0.26	2	-0.39	2	4
INPPL1	0	0	-10000	0	-10000	0	0
PREX1	-0.01	0.057	-10000	0	-0.31	36	36
ARHGEF6	-0.011	0.092	-10000	0	-0.79	15	15
ARHGEF7	0	0	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
NRAS	0.011	0.013	-10000	0	-0.29	2	2
FYN	-0.001	0.034	-10000	0	-0.79	2	2
ARF6	0	0	-10000	0	-10000	0	0
FGR	-0.001	0.025	-10000	0	-0.54	2	2
mol:Ca2+	0.039	0.029	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.001	0.018	-10000	0	-0.29	4	4
ZAP70	-0.031	0.12	-10000	0	-0.42	81	81
mol:IP3	0.047	0.038	-10000	0	-0.22	1	1
LYN	0	0	-10000	0	-10000	0	0
ARF1/GDP	0.038	0.032	-10000	0	-0.3	2	2
RhoA/GDP	-0.002	0.022	0.27	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	0.061	0.035	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-0.29	1	1
PLEKHA2	0.03	0.007	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PTEN	-0.001	0.033	-10000	0	-0.76	2	2
HSP90AA1	0	0.009	-10000	0	-0.29	1	1
ARF6/GTP	-0.001	0.021	0.3	2	-10000	0	2
RhoA/GTP	-0.001	0.021	0.25	2	-0.36	2	4
Src family/SYK family/BLNK-LAT	-0.011	0.056	-10000	0	-0.53	6	6
BLK	-0.044	0.11	-10000	0	-0.3	159	159
PDPK1	0	0	-10000	0	-10000	0	0
CYTH1	-0.001	0.021	0.26	2	-0.36	2	4
HCK	-0.004	0.033	-10000	0	-10000	0	0
CYTH3	-0.002	0.028	0.26	2	-0.41	4	6
CYTH2	-0.001	0.021	0.26	2	-0.36	2	4
KRAS	0.011	0.013	-10000	0	-0.29	2	2
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.005	0.055	-10000	0	-0.55	10	10
SGK1	-0.004	0.057	0.23	2	-0.7	7	9
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.034	0.033	-10000	0	-0.28	4	4
SOS1	0	0	-10000	0	-10000	0	0
SYK	0	0.009	-10000	0	-0.29	1	1
ARF6/GDP	-0.002	0.023	0.28	2	-10000	0	2
mol:PI-3-4-5-P3	-0.001	0.024	0.36	2	-0.38	2	4
ARAP3/RAP1A/GTP	-0.001	0.022	0.25	2	-0.38	2	4
VAV1	-0.003	0.043	-10000	0	-0.59	5	5
mol:PI-3-4-P2	0.022	0	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	-0.002	0.019	-10000	0	-0.39	2	2
PLEKHA1	0.03	0.017	-10000	0	-0.52	1	1
Rac1/GDP	0.038	0.032	-10000	0	-0.3	2	2
LAT	-0.005	0.048	-10000	0	-0.35	17	17
Rac1/GTP	-0.006	0.045	-10000	0	-0.37	15	15
ITK	-0.019	0.083	0.26	1	-0.43	38	39
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.059	0.065	0.24	1	-0.39	7	8
LCK	-0.02	0.1	-10000	0	-0.41	53	53
BTK	-0.001	0.021	0.26	2	-0.36	2	4

×

EPO 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
BCL2L1	0.058	0.076	-9999	-0.51	1	1
CRKL	0.028	0.05	-9999	-0.48	1	1
mol:DAG	-0.007	0.026	-9999	-0.39	1	1
HRAS	-0.006	0.022	-9999	-0.39	1	1
MAPK8	0.01	0.07	-9999	-0.5	9	9
RAP1A	0.028	0.05	-9999	-0.48	1	1
GAB1	0.028	0.05	-9999	-0.48	1	1
MAPK14	0.015	0.052	-9999	-10000	0	0
EPO	-0.036	0.11	-9999	-0.28	177	177
PLCG1	-0.007	0.026	-9999	-0.4	1	1
EPOR/TRPC2/IP3 Receptors	0.012	0.01	-9999	-0.28	1	1
RAPGEF1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.024	0.065	-9999	-0.62	6	6
GAB1/SHC/GRB2/SOS1	-0.008	0.022	-9999	-0.41	1	1
EPO/EPOR (dimer)	-0.027	0.067	-9999	-10000	0	0
IRS2	0.009	0.11	-9999	-0.46	47	47
STAT1	0.049	0.056	-9999	-0.5	1	1
STAT5B	-0.004	0.043	-9999	-0.43	4	4
cell proliferation	0.02	0.065	-9999	-0.46	9	9
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.011	0.044	-9999	-0.42	4	4
TEC	0.027	0.056	-9999	-0.48	4	4
SOCS3	-0.004	0.058	-9999	-0.79	6	6
STAT1 (dimer)	0.048	0.056	-9999	-0.49	1	1
JAK2	0.011	0.025	-9999	-0.8	1	1
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
EPO/EPOR (dimer)/JAK2	0.054	0.04	-9999	-0.51	1	1
EPO/EPOR	-0.027	0.067	-9999	-10000	0	0
LYN	0.013	0.002	-9999	-10000	0	0
TEC/VAV2	0.034	0.055	-9999	-0.46	4	4
elevation of cytosolic calcium ion concentration	0.012	0.01	-9999	-0.28	1	1
SHC1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.017	0.05	-9999	-10000	0	0
mol:IP3	-0.007	0.026	-9999	-0.39	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.03	0.096	-9999	-0.49	23	23
SH2B3	0.012	0.004	-9999	-10000	0	0
NFKB1	0.015	0.052	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.01	0.031	-9999	-0.32	7	7
PTPN6	0.021	0.052	-9999	-0.51	1	1
TEC/VAV2/GRB2	-0.01	0.034	-9999	-0.46	3	3
EPOR	0.012	0.01	-9999	-0.28	1	1
INPP5D	0	0	-9999	-10000	0	0
mol:GDP	-0.008	0.022	-9999	-0.42	1	1
SOS1	0	0	-9999	-10000	0	0
PLCG2	-0.002	0.035	-9999	-0.62	3	3
CRKL/CBL/C3G	-0.009	0.025	-9999	-0.44	1	1
VAV2	0.028	0.05	-9999	-0.48	1	1
CBL	0.028	0.05	-9999	-0.48	1	1
SHC/Grb2/SOS1	0.005	0.028	-9999	-0.44	1	1
STAT5A	-0.006	0.055	-9999	-0.47	9	9
GRB2	0	0.009	-9999	-0.29	1	1
STAT5 (dimer)	0.058	0.085	-9999	-0.56	5	5
LYN/PLCgamma2	-0.001	0.026	-9999	-0.6	2	2
PTPN11	0	0	-9999	-10000	0	0
BTK	0.028	0.051	-9999	-0.48	1	1
BCL2	0.036	0.19	-9999	-0.98	37	37

×

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

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
BAG4	-0.006	0.055	-9999	-0.43	14	14
Caspase 8 (4 units)	-0.01	0.052	-9999	-0.85	2	2
NEF	-0.006	0.028	-9999	-10000	0	0
NFKBIA	-0.001	0.011	-9999	-10000	0	0
BIRC3	0.035	0.081	-9999	-0.79	9	9
CYCS	0.04	0.06	-9999	-0.93	1	1
RIPK1	0	0	-9999	-10000	0	0
CD247	-0.025	0.12	-9999	-0.61	37	37
MAP2K7	0.042	0.049	-9999	-0.8	1	1
protein ubiquitination	0.066	0.034	-9999	-10000	0	0
CRADD	0	0	-9999	-10000	0	0
DAXX	0	0	-9999	-10000	0	0
FAS	-0.004	0.058	-9999	-0.79	6	6
BID	0.033	0.063	-9999	-1	1	1
NF-kappa-B/RelA/I kappa B alpha	-0.004	0.033	-9999	-10000	0	0
TRADD	0	0	-9999	-10000	0	0
MAP3K5	-0.003	0.048	-9999	-0.79	4	4
CFLAR	-0.001	0.024	-9999	-0.79	1	1
FADD	-0.004	0.034	-9999	-0.29	15	15
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.004	0.033	-9999	-10000	0	0
MAPK8	0.045	0.064	-9999	-0.48	10	10
APAF1	0	0	-9999	-10000	0	0
TRAF1	-0.001	0.015	-9999	-0.29	3	3
TRAF2	-0.001	0.018	-9999	-0.29	4	4
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.012	0.058	-9999	-0.33	24	24
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.002	0.03	-9999	-0.37	2	2
CHUK	0.068	0.035	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.005	0.049	-9999	-0.5	9	9
TCRz/NEF	-0.025	0.11	-9999	-0.51	41	41
TNF	-0.016	0.095	-9999	-0.46	38	38
FASLG	-0.007	0.15	-9999	-0.66	41	41
NFKB1	-0.001	0.011	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.069	-9999	-0.52	17	17
CASP6	-0.005	0.037	-9999	-0.68	2	2
CASP7	0.072	0.077	-9999	-0.62	9	9
RELA	-0.001	0.011	-9999	-10000	0	0
CASP2	0	0	-9999	-10000	0	0
CASP3	0.072	0.077	-9999	-0.6	10	10
TNFRSF1A	0	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.004	0.04	-9999	-0.6	4	4
CASP8	0	0	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
MAP3K14	0.063	0.038	-9999	-0.36	1	1
APAF-1/Caspase 9	-0.01	0.053	-9999	-0.5	9	9
BCL2	0.036	0.1	-9999	-0.42	44	44

×

PDGFR-beta signaling pathway

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
S1P1/Sphingosine-1-phosphate	-0.004	0.045	-9999	-0.56	6	6
PDGFB-D/PDGFRB/SLAP	-0.004	0.041	-9999	-0.6	4	4
PDGFB-D/PDGFRB/APS/CBL	-0.008	0.043	-9999	-0.51	4	4
AKT1	-0.012	0.052	-9999	-0.49	4	4
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.035	0.052	-9999	-0.58	6	6
PIK3CA	0	0.009	-9999	-0.29	1	1
FGR	-0.003	0.038	-9999	-0.53	5	5
mol:Ca2+	0.033	0.048	-9999	-0.68	4	4
MYC	0.039	0.14	-9999	-0.8	28	28
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.003	0.028	-9999	-0.42	4	4
LRP1/PDGFRB/PDGFB	-0.008	0.07	-9999	-0.58	15	15
GRB10	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0.033	0.048	-9999	-0.69	4	4
PTEN	-0.001	0.034	-9999	-0.79	2	2
GRB2	0	0.009	-9999	-0.29	1	1
GRB7	-0.023	0.085	-9999	-0.31	79	79
PDGFB-D/PDGFRB/SHP2	-0.002	0.036	-9999	-0.6	4	4
PDGFB-D/PDGFRB/GRB10	-0.002	0.036	-9999	-0.6	4	4
cell cycle arrest	-0.004	0.04	-9999	-0.6	4	4
HRAS	-0.003	0.028	-9999	-0.29	10	10
HIF1A	0.05	0.061	-9999	-0.43	4	4
GAB1	0.035	0.055	-9999	-0.67	4	4
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.04	0.053	-9999	-0.61	4	4
PDGFB-D/PDGFRB	-0.003	0.035	-9999	-0.52	4	4
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.002	0.036	-9999	-0.6	4	4
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.005	0.049	-9999	-0.57	6	6
positive regulation of MAPKKK cascade	-0.002	0.036	-9999	-0.6	4	4
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
mol:IP3	0.033	0.049	-9999	-0.7	4	4
E5	0	0.001	-9999	-10000	0	0
CSK	0	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.017	0.067	-9999	-0.6	7	7
SHB	-0.001	0.025	-9999	-0.54	2	2
BLK	-0.002	0.049	-9999	-0.58	7	7
PTPN2	0.002	0.004	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.002	0.036	-9999	-0.6	4	4
BCAR1	0	0	-9999	-10000	0	0
VAV2	0.04	0.062	-9999	-0.61	5	5
CBL	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.002	0.036	-9999	-0.6	4	4
LCK	-0.01	0.08	-9999	-0.63	16	16
PDGFRB	0.009	0.049	-9999	-0.79	4	4
ACP1	0	0	-9999	-10000	0	0
HCK	-0.002	0.033	-9999	-0.5	4	4
ABL1	0.034	0.049	-9999	-0.63	4	4
PDGFB-D/PDGFRB/CBL	0.034	0.06	-9999	-0.79	4	4
PTPN1	-0.001	0.03	-9999	-0.3	1	1
SNX15	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
STAT1	-0.005	0.038	-9999	-0.29	19	19
cell proliferation	0.041	0.12	-9999	-0.69	28	28
SLA	-0.003	0.029	-9999	-0.29	11	11
actin cytoskeleton reorganization	-0.002	0.028	-9999	-0.4	1	1
SRC	-0.002	0.033	-9999	-0.5	4	4
PI3K	-0.014	0.059	-9999	-0.56	4	4
PDGFB-D/PDGFRB/GRB7/SHC	-0.013	0.054	-9999	-0.52	7	7
SH2B2	-0.013	0.061	-9999	-0.29	49	49
PLCgamma1/SPHK1	0.036	0.054	-9999	-0.61	6	6
LYN	-0.002	0.033	-9999	-0.5	4	4
LRP1	-0.009	0.085	-9999	-0.79	13	13
SOS1	0	0	-9999	-10000	0	0
STAT5B	-0.002	0.041	-9999	-0.79	3	3
STAT5A	-0.006	0.067	-9999	-0.79	8	8
NCK1-2/p130 Cas	-0.002	0.026	-9999	-0.41	4	4
SPHK1	0.004	0.054	-9999	-0.33	23	23
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.033	0.049	-9999	-0.7	4	4
PLCG1	0.033	0.05	-9999	-0.72	4	4
NHERF/PDGFRB	-0.015	0.052	-9999	-0.51	4	4
YES1	-0.003	0.038	-9999	-0.52	5	5
cell migration	-0.015	0.052	-9999	-0.51	4	4
SHC/Grb2/SOS1	-0.002	0.026	-9999	-0.41	4	4
SLC9A3R2	-0.001	0.02	-9999	-0.29	5	5
SLC9A3R1	-0.026	0.083	-9999	-0.29	97	97
NHERF1-2/PDGFRB/PTEN	-0.014	0.049	-9999	-0.47	6	6
FYN	-0.003	0.06	-9999	-0.89	4	4
DOK1	0.029	0.035	-9999	-0.47	4	4
HRAS/GTP	-0.002	0.019	-9999	-0.2	10	10
PDGFB	0	0	-9999	-10000	0	0
RAC1	0.046	0.082	-9999	-0.44	28	28
PRKCD	0.03	0.035	-9999	-0.47	4	4
FER	0.025	0.061	-9999	-0.48	15	15
MAPKKK cascade	-0.002	0.027	-9999	-0.4	4	4
RASA1	0.03	0.035	-9999	-0.47	4	4
NCK1	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
p62DOK/Csk	-0.002	0.029	-9999	-0.43	4	4
PDGFB-D/PDGFRB/SHB	-0.003	0.041	-9999	-0.6	5	5
chemotaxis	0.034	0.048	-9999	-0.6	4	4
STAT1-3-5/STAT1-3-5	-0.008	0.054	-9999	-0.46	13	13
Bovine Papilomavirus E5/PDGFRB	-0.002	0.037	-9999	-0.61	4	4
PTPRJ	0	0	-9999	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	-0.001	0.024	-9999	-0.79	1	1
SMAD2	0.014	0.004	-9999	-10000	0	0
SMAD3	0.041	0	-9999	-10000	0	0
SMAD3/SMAD4	0.004	0.015	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0.016	-9999	-0.52	1	1
SMAD2/SMAD2/SMAD4	-0.009	0.031	-9999	-0.52	1	1
PPM1A	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
SMAD2/SMAD4	0	0.015	-9999	-0.47	1	1
MAP3K1	-0.001	0.024	-9999	-0.79	1	1
TRAP-1/SMAD4	-0.01	0.076	-9999	-0.6	18	18
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	-0.012	0.097	-9999	-0.79	17	17
UBE2I	0	0	-9999	-10000	0	0
NUP153	0	0.009	-9999	-0.29	1	1
KPNA2	-0.029	0.087	-9999	-0.29	108	108
PIAS4	0	0	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.046	0.045	-10000	0	-0.55	1	1
BAG4	-0.006	0.055	-10000	0	-0.43	14	14
BAD	0.032	0.017	-10000	0	-10000	0	0
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.077	-10000	0	-0.5	21	21
BAX	0.032	0.018	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.015	0.012	-10000	0	-0.1	2	2
IKBKB	0.052	0.043	-10000	0	-0.51	1	1
MAP2K2	0.044	0.024	-10000	0	-0.46	1	1
MAP2K1	0.044	0.024	-10000	0	-0.46	1	1
SMPD1	0.021	0.012	-10000	0	-0.11	1	1
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.051	0.048	-10000	0	-0.45	3	3
MAP2K4	0.038	0.025	-10000	0	-0.38	2	2
protein ubiquitination	0.054	0.044	-10000	0	-0.52	1	1
EnzymeConsortium:2.7.1.37	0.049	0.026	-10000	0	-0.48	1	1
response to UV	0	0	-10000	0	-0.003	1	1
RAF1	0.039	0.024	-10000	0	-0.49	1	1
CRADD	0.011	0.002	-10000	0	-10000	0	0
mol:ceramide	0.025	0.017	-10000	0	-0.14	2	2
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0.011	0.002	-10000	0	-10000	0	0
MAP3K1	0.032	0.021	-10000	0	-0.4	1	1
TRADD	0.011	0.002	-10000	0	-10000	0	0
RELA/p50	0	0	-10000	0	-10000	0	0
MAPK3	0.047	0.023	-10000	0	-0.45	1	1
MAPK1	0.047	0.023	-10000	0	-0.45	1	1
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.044	0.049	-10000	0	-0.47	3	3
KSR1	0.032	0.024	-10000	0	-0.52	1	1
MAPK8	0.041	0.047	-10000	0	-0.41	10	10
TRAF2	-0.001	0.018	-10000	0	-0.29	4	4
response to radiation	0	0	-10000	0	-0.002	1	1
CHUK	0.052	0.043	-10000	0	-0.51	1	1
TNF R/SODD	-0.004	0.04	-10000	0	-0.6	4	4
TNF	-0.005	0.097	-10000	0	-0.46	38	38
CYCS	0.037	0.025	0.15	32	-10000	0	32
IKBKG	0.052	0.043	-10000	0	-0.51	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.039	0.047	-10000	0	-0.35	9	9
RELA	0	0	-10000	0	-10000	0	0
RIPK1	0	0.001	-10000	0	-10000	0	0
AIFM1	0.037	0.025	0.15	32	-10000	0	32
TNF/TNF R/SODD	-0.013	0.069	-10000	0	-0.52	17	17
TNFRSF1A	0	0.001	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-0.002	1	1
CASP8	0.028	0.012	-10000	0	-10000	0	0
NSMAF	0.046	0.045	-10000	0	-0.54	1	1
response to hydrogen peroxide	0	0	-10000	0	-0.003	1	1
BCL2	-0.027	0.14	-10000	0	-0.79	37	37

×

FoxO family signaling

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
G6PC	0.029	0.039	-9999	-10000	0	0
PLK1	0.004	0.12	-9999	-0.82	2	2
CDKN1B	0.079	0.072	-9999	-0.54	3	3
FOXO3	0.039	0.11	-9999	-0.56	12	12
KAT2B	0.008	0.028	-9999	-0.83	1	1
FOXO1/SIRT1	0.007	0.039	-9999	-0.32	12	12
CAT	0.041	0.13	-9999	-1.1	7	7
CTNNB1	0	0	-9999	-10000	0	0
AKT1	0.015	0.011	-9999	-10000	0	0
FOXO1	0.031	0.042	-9999	-0.36	12	12
MAPK10	-0.038	0.18	-9999	-0.44	171	171
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.063	0.089	-9999	-0.41	1	1
response to oxidative stress	0.005	0.012	-9999	-10000	0	0
FOXO3A/SIRT1	-0.016	0.069	-9999	-0.52	8	8
XPO1	0.012	0.001	-9999	-10000	0	0
EP300	0.01	0.005	-9999	-10000	0	0
BCL2L11	0.028	0.02	-9999	-10000	0	0
FOXO1/SKP2	-0.004	0.033	-9999	-0.32	12	12
mol:GDP	0.005	0.012	-9999	-10000	0	0
RAN	0.013	0.001	-9999	-10000	0	0
GADD45A	0.068	0.064	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.069	0.027	-9999	-10000	0	0
MST1	-0.003	0.092	-9999	-0.59	22	22
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.049	0.045	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
MAPK8	0.033	0.044	-9999	-0.44	9	9
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	0.015	-9999	-0.29	3	3
SIRT1	0.004	0.009	-9999	-10000	0	0
SOD2	0.09	0.079	-9999	-0.45	1	1
RBL2	0.06	0.083	-9999	-0.56	1	1
RAL/GDP	0.012	0.016	-9999	-10000	0	0
CHUK	0.009	0.013	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
RAL/GTP	0.031	0.01	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
FASLG	0.002	0.18	-9999	-1.5	15	15
SKP2	0	0	-9999	-10000	0	0
USP7	0.013	0.001	-9999	-10000	0	0
IKBKB	0.008	0.018	-9999	-0.28	2	2
CCNB1	0.032	0.12	-9999	-0.62	7	7
FOXO1-3a-4/beta catenin	-0.009	0.043	-9999	-0.41	7	7
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.033	-9999	-0.32	12	12
CSNK1A1	0	0	-9999	-10000	0	0
SGK1	0.004	0.065	-9999	-0.79	7	7
CSNK1G3	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
ZFAND5	0.068	0.079	-9999	-10000	0	0
SFN	-0.016	0.099	-9999	-0.5	36	36
CDK2	0.004	0.006	-9999	-10000	0	0
FOXO3A/14-3-3	0.044	0.048	-9999	-10000	0	0
CREBBP	0.004	0.006	-9999	-10000	0	0
FBXO32	0.042	0.12	-9999	-1.1	5	5
BCL6	0.054	0.13	-9999	-1.2	7	7
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 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
BCL3/RelA	-0.001	0.01	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.007	0.058	-9999	-0.52	14	14
NF kappa B1 p50/RelA/I kappa B alpha	-0.003	0.024	-9999	-10000	0	0
NFKBIA	0.024	0.034	-9999	-0.27	13	13
MAPK14	0	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0	0.006	-9999	-10000	0	0
ARRB2	0.017	0	-9999	-10000	0	0
REL	-0.01	0.089	-9999	-0.79	14	14
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	-0.001	0.01	-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	-0.29	1	1
NF kappa B1 p50 dimer	0	0.008	-9999	-10000	0	0
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
NFKB1	0.022	0.009	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.03	0.033	-9999	-0.26	13	13
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.003	0.023	-9999	-10000	0	0
SRC	0	0.009	-9999	-0.29	1	1
PI3K	-0.008	0.068	-9999	-0.6	14	14
NF kappa B1 p50/RelA	-0.004	0.029	-9999	-0.26	13	13
IKBKB	-0.001	0.013	-9999	-0.29	2	2
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
SYK	0	0.009	-9999	-0.29	1	1
I kappa B alpha/PIK3R1	-0.009	0.056	-9999	-0.44	14	14
cell death	-0.003	0.022	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.007	0.058	-9999	-0.52	14	14
LCK	-0.02	0.1	-9999	-0.41	53	53
BCL3	-0.001	0.015	-9999	-10000	0	0

×

Canonical NF-kappaB 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
FBXW11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.077	0.036	-9999	-10000	0	0
ERC1	0	0	-9999	-10000	0	0
RIP2/NOD2	-0.007	0.04	-9999	-0.48	2	2
NFKBIA	0.047	0	-9999	-10000	0	0
BIRC2	0	0	-9999	-10000	0	0
IKBKB	-0.001	0.013	-9999	-0.29	2	2
RIPK2	-0.001	0.02	-9999	-0.29	5	5
IKBKG	0	0.008	-9999	-10000	0	0
IKK complex/A20	-0.003	0.043	-9999	-10000	0	0
NEMO/A20/RIP2	-0.001	0.02	-9999	-0.29	5	5
XPO1	0	0	-9999	-10000	0	0
NEMO/ATM	0	0.007	-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	0.007	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.01	0.056	-9999	-0.31	35	35
NFKB1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
MALT1	0	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
TNF/TNFR1A	-0.011	0.07	-9999	-0.6	13	13
TRAF6	0	0	-9999	-10000	0	0
PRKCA	-0.021	0.13	-9999	-0.76	31	31
CHUK	0	0	-9999	-10000	0	0
UBE2D3	0	0	-9999	-10000	0	0
TNF	-0.016	0.095	-9999	-0.46	38	38
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	0.008	-9999	-10000	0	0
CYLD	0	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.009	0.06	-9999	-0.37	29	29

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.004	0.053	-9999	-0.48	13	13
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.005	0.044	-9999	-0.4	13	13
SUMO1	0	0	-9999	-10000	0	0
ZFPM1	-0.002	0.026	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0.001	-9999	-10000	0	0
FKBP3	0	0	-9999	-10000	0	0
Histones	-0.003	0.022	-9999	-10000	0	0
YY1/LSF	-0.001	0.017	-9999	-0.4	2	2
SMG5	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.005	0.039	-9999	-10000	0	0
I kappa B alpha/HDAC1	-0.004	0.026	-9999	-10000	0	0
SAP18	0	0	-9999	-10000	0	0
RELA	-0.004	0.034	-9999	-0.31	13	13
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0	0.009	-9999	-0.29	1	1
HDAC3/TR2	-0.004	0.026	-9999	-10000	0	0
NuRD/MBD3 Complex	0	0.006	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.004	0.03	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.024	0.13	-9999	-0.63	41	41
GATA1	-0.005	0.037	-9999	-0.29	18	18
Mad/Max	0	0.006	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0	0.007	-9999	-10000	0	0
RBBP7	-0.002	0.025	-9999	-0.29	8	8
NPC	0	0	-9999	-10000	0	0
RBBP4	-0.001	0.024	-9999	-0.79	1	1
MAX	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NFKBIA	-0.004	0.03	-9999	-10000	0	0
KAT2B	-0.001	0.024	-9999	-0.79	1	1
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0	0.008	-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	-0.29	4	4
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	-0.001	0.024	-9999	-0.79	1	1
YY1/HDAC3	-0.003	0.024	-9999	-10000	0	0
YY1/HDAC2	0	0.009	-9999	-0.29	1	1
YY1/HDAC1	0	0.009	-9999	-0.29	1	1
NuRD/MBD2 Complex (MeCP1)	0	0.006	-9999	-10000	0	0
PPARG	-0.095	0.17	-9999	-0.37	277	277
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	0.026	-9999	-10000	0	0
MBD3L2	-0.001	0.013	-9999	-0.29	2	2
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0	0.007	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC3	-0.004	0.03	-9999	-10000	0	0
HDAC2	0	0	-9999	-10000	0	0
YY1	0.029	0.011	-9999	-0.35	1	1
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	-0.29	1	1
STAT3	0.025	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	-0.001	0.016	-9999	-0.46	1	1
YY1/SAP30/HDAC1	-0.001	0.01	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.025	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.03	-9999	-10000	0	0
histone deacetylation	0.046	0.008	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.003	0.023	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GATAD2B	0	0	-9999	-10000	0	0
GATAD2A	0	0	-9999	-10000	0	0
GATA2/HDAC3	-0.017	0.079	-9999	-0.47	28	28
GATA1/HDAC1	-0.003	0.024	-9999	-10000	0	0
GATA1/HDAC3	-0.006	0.031	-9999	-10000	0	0
CHD4	0	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.011	0.07	-9999	-0.6	13	13
SIN3/HDAC complex/Mad/Max	0	0.006	-9999	-10000	0	0
NuRD Complex	0	0.007	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.021	-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	0.001	-9999	-10000	0	0
HDAC complex	-0.001	0.017	-9999	-0.47	1	1
GATA1/Fog1	-0.005	0.029	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.016	0.095	-9999	-0.46	38	38
negative regulation of cell growth	0.046	0.009	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0	0.006	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.006	0.046	-9999	-0.42	13	13
SIN3/HDAC complex/NCoR1	0	0.01	-9999	-10000	0	0
TFCP2	-0.001	0.024	-9999	-0.79	1	1
NR2C1	0	0	-9999	-10000	0	0
MBD3	0	0.009	-9999	-0.29	1	1
MBD2	0	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
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	0.028	-9999	-0.29	10	10
RAC1	0	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.008	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	0.032	-9999	-0.47	2	2
lamellipodium assembly	-0.005	0.052	-9999	-0.46	14	14
PIK3CA	0	0.009	-9999	-0.29	1	1
PI3K	-0.008	0.068	-9999	-0.6	14	14
ARF6	0	0	-9999	-10000	0	0
TLN1	0	0	-9999	-10000	0	0
PXN	0.022	0	-9999	-10000	0	0
PIK3R1	-0.01	0.089	-9999	-0.79	14	14
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	0.011	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.009	0.058	-9999	-0.32	32	32
ARF6/GDP	0	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.007	0.049	-9999	-0.44	13	13
p130Cas/Crk/Dock1	0	0	-9999	-10000	0	0
VCAM1	-0.011	0.088	-9999	-0.63	19	19
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	0.02	-9999	-0.29	5	5
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.001	0.01	-9999	-10000	0	0
Rac1/GTP	-0.006	0.058	-9999	-0.51	14	14

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.003	0.019	-9999	-10000	0	0
CLOCK	0.006	0.083	-9999	-0.78	12	12
TIMELESS/CRY2	-0.001	0.01	-9999	-10000	0	0
DEC1/BMAL1	-0.001	0.014	-9999	-10000	0	0
ATR	0	0	-9999	-10000	0	0
NR1D1	0.041	0.017	-9999	-10000	0	0
ARNTL	0.014	0.002	-9999	-10000	0	0
TIMELESS	0.04	0.019	-9999	-10000	0	0
NPAS2	0.009	0.061	-9999	-0.78	6	6
CRY2	0	0	-9999	-10000	0	0
mol:CO	-0.014	0.003	-9999	-10000	0	0
CHEK1	-0.006	0.043	-9999	-0.29	24	24
mol:HEME	0.014	0.003	-9999	-10000	0	0
PER1	-0.015	0.11	-9999	-0.79	21	21
BMAL/CLOCK/NPAS2	0.03	0.07	-9999	-0.51	18	18
BMAL1/CLOCK	0.042	0.053	-9999	-10000	0	0
S phase of mitotic cell cycle	-0.003	0.019	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	-0.003	0.019	-9999	-10000	0	0
mol:NADPH	0.014	0.003	-9999	-10000	0	0
PER1/TIMELESS	-0.01	0.062	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.002	0.022	-9999	-0.29	6	6

×

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	0.027	0.047	-10000	0	-10000	0	0
regulation of axonogenesis	-0.023	0.034	0.31	10	-10000	0	10
myoblast fusion	0.008	0.026	-10000	0	-10000	0	0
mol:GTP	-0.005	0.016	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.009	0.031	-10000	0	-10000	0	0
ARF1/GTP	-0.003	0.008	-10000	0	-10000	0	0
mol:GM1	0.006	0.015	-10000	0	-10000	0	0
mol:Choline	0.02	0.052	-10000	0	-0.51	10	10
lamellipodium assembly	-0.004	0.031	-10000	0	-10000	0	0
MAPK3	0.02	0.026	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.009	0.031	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
ARF6/GDP	-0.008	0.026	-10000	0	-10000	0	0
ARF1/GDP	-0.004	0.024	-10000	0	-10000	0	0
ARF6	0.007	0.008	-10000	0	-10000	0	0
RAB11A	-0.001	0.013	-10000	0	-0.29	2	2
TIAM1	0.011	0.019	-10000	0	-0.29	4	4
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.02	0.026	-10000	0	-10000	0	0
actin filament bundle formation	0.006	0.021	-10000	0	-10000	0	0
KALRN	-0.011	0.065	-10000	0	-0.47	20	20
RAB11FIP3/RAB11A	0	0.008	-10000	0	-10000	0	0
RhoA/GDP	-0.006	0.021	-10000	0	-10000	0	0
NME1	-0.004	0.067	-10000	0	-0.29	56	56
Rac1/GDP	-0.006	0.021	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.005	0.016	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.004	0.031	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
liver development	-0.005	0.016	-10000	0	-10000	0	0
ARF6/GTP	-0.005	0.016	-10000	0	-10000	0	0
RhoA/GTP	-0.003	0.008	-10000	0	-10000	0	0
mol:GDP	-0.006	0.029	-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	0.011	0.058	-10000	0	-0.57	10	10
RAB11FIP3	0	0	-10000	0	-10000	0	0
tube morphogenesis	-0.004	0.031	-10000	0	-10000	0	0
ruffle organization	0.023	0.034	-10000	0	-0.31	10	10
regulation of epithelial cell migration	-0.005	0.016	-10000	0	-10000	0	0
PLD2	0.016	0.014	-10000	0	-10000	0	0
PIP5K1A	-0.004	0.03	-10000	0	-0.31	10	10
mol:Phosphatidic acid	0.02	0.052	-10000	0	-0.51	10	10
Rac1/GTP	-0.004	0.031	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.13	0.12	-9999	-0.52	9	9
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	-0.34	13	13
YWHAZ	-0.001	0.015	-9999	-0.29	3	3
CALM1	0	0	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
TBC1D4	0.019	0.046	-9999	-0.6	6	6
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	-0.003	0.029	-9999	-0.29	11	11
PRKCI	0	0.009	-9999	-0.29	1	1
AS160/CaM/Ca2+	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
GYS1	0.032	0	-9999	-10000	0	0
PRKCZ	-0.001	0.024	-9999	-0.79	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	-0.13	0.16	-9999	-0.38	13	13
STX4	0	0	-9999	-10000	0	0
GSK3B	0.025	0	-9999	-10000	0	0
SFN	-0.016	0.099	-9999	-0.5	36	36
LNPEP	-0.006	0.067	-9999	-0.79	8	8
YWHAE	0	0	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0	0.009	-9999	-0.29	1	1
PLK4	-0.012	0.059	-9999	-10000	0	0
regulation of centriole replication	0.013	0.042	-9999	-10000	0	0

×

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	0.011	-9999	-0.36	1	1
MDM2/SUMO1	-0.001	0.007	-9999	-10000	0	0
HDAC4	-0.001	0.024	-9999	-0.79	1	1
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
SUMO1	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0	0.002	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.029	0.001	-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	0.013	-9999	-0.43	1	1
SUMO1/HDAC1	0	0.001	-9999	-10000	0	0
RANGAP1	0	0.009	-9999	-0.29	1	1
MDM2/SUMO1/SUMO1	-0.001	0.008	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0	0.001	-9999	-10000	0	0
Ran/GTP	0	0.001	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	-0.001	0.02	-9999	-0.29	5	5
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	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	-0.001	0.008	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.02	0	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	-0.001	0.018	-9999	-0.29	4	4
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0.003	-9999	-10000	0	0
CD4	0	0	-9999	-10000	0	0
CLTA	0	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.01	0.017	-9999	-0.2	7	7
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.001	0.008	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	-0.001	0.009	-9999	-10000	0	0
AP2M1	0	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	-0.001	0.01	-9999	-10000	0	0
ARFIP2	0	0	-9999	-10000	0	0
COPA	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.025	0.002	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0	0.004	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0	0.001	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.01	0.017	-9999	-0.2	7	7
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.01	0.017	-9999	-0.2	7	7
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0	0	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.001	0.01	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAP3K14	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.002	0.018	-9999	-10000	0	0
RELB	-0.003	0.028	-9999	-0.29	10	10
NFKB2	0	0.009	-9999	-0.29	1	1
NF kappa B2 p52/RelB	-0.002	0.015	-9999	-10000	0	0
regulation of B cell activation	-0.002	0.015	-9999	-10000	0	0

pid_entity	TCGA.Z7.A8R6	TCGA.Z7.A8R5	TCGA.XX.A89A	TCGA.XX.A899
109_MAP3K5	-0.27	0.054	0.054	0.054
47_PPARGC1A	-0.79	0	0	0
105_BMP4	0	0	0	0
105_BMP6	0	0	0	0
105_BMP7	0	0	0	0
105_BMP2	-0.79	0	0	0
131_RELN/VLDLR	-0.47	-0.47	0	0
30_TGFB1/TGF beta receptor Type II	0.013	0	0.013	0.012
84_STAT5B	-0.1	-0.073	0.032	0.046
84_STAT5A	-0.1	-0.073	0.032	0.046