Breast Invasive Carcinoma: PARADIGM pathway analysis of mRNA expression and copy number data

Pathway.Name	Avg.Num.Perturbations
Signaling events regulated by Ret tyrosine kinase	96
Signaling events mediated by Stem cell factor receptor (c-Kit)	89
Endothelins	75
Osteopontin-mediated events	71
IGF1 pathway	70
IL4-mediated signaling events	69
FOXM1 transcription factor network	67
Plasma membrane estrogen receptor signaling	65
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	62
EGFR-dependent Endothelin signaling events	61

Pathway.Name	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
Signaling events regulated by Ret tyrosine kinase	96	7913	82	-0.16	0.036	1000	-1000	-0.042	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	89	6957	78	-0.31	0.13	1000	-1000	-0.043	-1000
Endothelins	75	7230	96	-0.18	0.035	1000	-1000	-0.038	-1000
Osteopontin-mediated events	71	2698	38	-0.14	0.038	1000	-1000	-0.016	-1000
IGF1 pathway	70	4008	57	-0.08	0.052	1000	-1000	-0.032	-1000
IL4-mediated signaling events	69	6280	91	-0.53	0.43	1000	-1000	-0.042	-1000
FOXM1 transcription factor network	67	3464	51	-0.43	0.033	1000	-1000	-0.059	-1000
Plasma membrane estrogen receptor signaling	65	5669	86	-0.22	0.21	1000	-1000	-0.038	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	62	4218	68	-0.34	0.15	1000	-1000	-0.046	-1000
EGFR-dependent Endothelin signaling events	61	1295	21	-0.074	0.047	1000	-1000	-0.017	-1000
Glucocorticoid receptor regulatory network	57	6555	114	-0.39	0.19	1000	-1000	-0.044	-1000
Syndecan-1-mediated signaling events	56	1927	34	-0.13	0.041	1000	-1000	-0.018	-1000
HIF-1-alpha transcription factor network	53	4064	76	-0.18	0.049	1000	-1000	-0.004	-1000
Fc-epsilon receptor I signaling in mast cells	50	4852	97	-0.097	0.035	1000	-1000	-0.049	-1000
TCR signaling in naïve CD8+ T cells	49	4600	93	-0.074	0.047	1000	-1000	-0.03	-1000
Signaling events mediated by the Hedgehog family	48	2520	52	-0.098	0.051	1000	-1000	-0.021	-1000
Thromboxane A2 receptor signaling	48	5104	105	-0.11	0.061	1000	-1000	-0.032	-1000
IL12-mediated signaling events	46	4012	87	-0.26	0.042	1000	-1000	-0.029	-1000
IL27-mediated signaling events	46	2353	51	-0.2	0.1	1000	-1000	-0.045	-1000
IL23-mediated signaling events	46	2781	60	-0.21	0.036	1000	-1000	-0.044	-1000
Nongenotropic Androgen signaling	45	2378	52	-0.12	0.063	1000	-1000	-0.018	-1000
IL6-mediated signaling events	44	3369	75	-0.14	0.037	1000	-1000	-0.032	-1000
FAS signaling pathway (CD95)	42	1986	47	-0.1	0.048	1000	-1000	-0.028	-1000
Noncanonical Wnt signaling pathway	41	1090	26	-0.071	0.035	1000	-1000	-0.047	-1000
Stabilization and expansion of the E-cadherin adherens junction	40	3033	74	-0.095	0.058	1000	-1000	-0.049	-1000
Syndecan-4-mediated signaling events	39	2675	67	-0.06	0.09	1000	-1000	-0.028	-1000
Wnt signaling	38	268	7	-0.071	0.03	1000	-1000	-0.015	-1000
LPA receptor mediated events	37	3852	102	-0.078	0.035	1000	-1000	-0.078	-1000
Arf6 signaling events	36	2261	62	-0.069	0.079	1000	-1000	-0.012	-1000
Ephrin B reverse signaling	35	1711	48	-0.12	0.071	1000	-1000	-0.034	-1000
Signaling mediated by p38-gamma and p38-delta	35	530	15	-0.056	0.033	1000	-1000	-0.028	-1000
TCGA08_p53	34	243	7	-0.029	0.026	1000	-1000	-0.003	-1000
E-cadherin signaling events	34	173	5	-0.012	0.028	1000	-1000	0.02	-1000
ErbB4 signaling events	33	2328	69	-0.11	0.06	1000	-1000	-0.016	-1000
Coregulation of Androgen receptor activity	32	2503	76	-0.15	0.054	1000	-1000	-0.029	-1000
PLK2 and PLK4 events	32	97	3	-0.015	0.03	1000	-1000	0	-1000
IL2 signaling events mediated by PI3K	32	1879	58	-0.23	0.035	1000	-1000	-0.032	-1000
Canonical Wnt signaling pathway	32	1653	51	-0.15	0.089	1000	-1000	-0.029	-1000
E-cadherin signaling in keratinocytes	32	1394	43	-0.061	0.036	1000	-1000	-0.022	-1000
Signaling events mediated by PTP1B	31	2369	76	-0.089	0.06	1000	-1000	-0.037	-1000
Integrins in angiogenesis	31	2628	84	-0.12	0.058	1000	-1000	-0.022	-1000
E-cadherin signaling in the nascent adherens junction	31	2367	76	-0.082	0.056	1000	-1000	-0.048	-1000
Syndecan-2-mediated signaling events	30	2127	69	-0.019	0.047	1000	-1000	-0.025	-1000
Cellular roles of Anthrax toxin	29	1139	39	-0.075	0.035	1000	-1000	-0.016	-1000
amb2 Integrin signaling	29	2385	82	-0.05	0.046	1000	-1000	-0.017	-1000
Regulation of nuclear SMAD2/3 signaling	28	3906	136	-0.19	0.066	1000	-1000	-0.034	-1000
TCGA08_retinoblastoma	28	227	8	-0.011	0.023	1000	-1000	-0.004	-1000
Caspase cascade in apoptosis	27	2045	74	-0.067	0.047	1000	-1000	-0.028	-1000
BMP receptor signaling	27	2210	81	-0.12	0.067	1000	-1000	-0.019	-1000
Nectin adhesion pathway	27	1707	63	-0.047	0.053	1000	-1000	-0.027	-1000
Reelin signaling pathway	27	1512	56	-0.071	0.068	1000	-1000	-0.019	-1000
VEGFR1 specific signals	26	1498	56	-0.028	0.036	1000	-1000	-0.024	-1000
Visual signal transduction: Rods	26	1382	52	-0.066	0.066	1000	-1000	-0.018	-1000
Aurora B signaling	26	1756	67	-0.065	0.052	1000	-1000	-0.039	-1000
IL1-mediated signaling events	25	1552	62	-0.029	0.074	1000	-1000	-0.03	-1000
BCR signaling pathway	25	2478	99	-0.1	0.065	1000	-1000	-0.042	-1000
mTOR signaling pathway	24	1286	53	-0.067	0.044	1000	-1000	-0.035	-1000
PDGFR-alpha signaling pathway	23	1045	44	-0.14	0.049	1000	-1000	-0.027	-1000
Arf6 downstream pathway	22	976	43	-0.047	0.048	1000	-1000	-0.028	-1000
FOXA2 and FOXA3 transcription factor networks	22	1036	46	-0.2	0.043	1000	-1000	-0.031	-1000
PLK1 signaling events	22	1931	85	-0.073	0.051	1000	-1000	-0.019	-1000
S1P1 pathway	22	796	36	-0.034	0.036	1000	-1000	-0.025	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	22	990	45	-0.043	0.055	1000	-1000	-0.028	-1000
Visual signal transduction: Cones	21	825	38	-0.022	0.05	1000	-1000	0	-1000
Presenilin action in Notch and Wnt signaling	21	1291	61	-0.2	0.07	1000	-1000	-0.043	-1000
Glypican 1 network	21	1037	48	-0.023	0.049	1000	-1000	-0.021	-1000
IFN-gamma pathway	21	1480	68	-0.059	0.058	1000	-1000	-0.033	-1000
Ceramide signaling pathway	20	1564	76	-0.069	0.068	1000	-1000	-0.02	-1000
TRAIL signaling pathway	20	983	48	-0.023	0.036	1000	-1000	-0.022	-1000
Calcium signaling in the CD4+ TCR pathway	20	645	31	-0.036	0.045	1000	-1000	-0.041	-1000
Insulin Pathway	20	1528	74	-0.063	0.079	1000	-1000	-0.025	-1000
Class I PI3K signaling events	19	1457	73	-0.06	0.044	1000	-1000	-0.02	-1000
PDGFR-beta signaling pathway	19	1925	97	-0.066	0.066	1000	-1000	-0.042	-1000
ErbB2/ErbB3 signaling events	18	1207	65	-0.046	0.047	1000	-1000	-0.054	-1000
ceramide signaling pathway	18	920	49	-0.057	0.048	1000	-1000	-0.029	-1000
RXR and RAR heterodimerization with other nuclear receptor	18	961	52	-0.057	0.061	1000	-1000	-0.026	-1000
Regulation of Telomerase	18	1842	102	-0.15	0.062	1000	-1000	-0.044	-1000
Ras signaling in the CD4+ TCR pathway	18	312	17	-0.002	0.05	1000	-1000	-0.011	-1000
p75(NTR)-mediated signaling	16	2025	125	-0.047	0.086	1000	-1000	-0.039	-1000
EPO signaling pathway	16	890	55	-0.11	0.046	1000	-1000	-0.026	-1000
Syndecan-3-mediated signaling events	16	573	35	-0.031	0.068	1000	-1000	-0.03	-1000
EPHB forward signaling	16	1374	85	-0.046	0.11	1000	-1000	-0.047	-1000
Regulation of Androgen receptor activity	15	1066	70	-0.14	0.047	1000	-1000	-0.038	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	14	793	54	-0.036	0.049	1000	-1000	-0.022	-1000
Hedgehog signaling events mediated by Gli proteins	14	967	65	-0.024	0.076	1000	-1000	-0.027	-1000
HIF-2-alpha transcription factor network	14	610	43	-0.11	0.11	1000	-1000	-0.035	-1000
FoxO family signaling	14	934	64	-0.092	0.048	1000	-1000	-0.024	-1000
Signaling events mediated by VEGFR1 and VEGFR2	14	1823	125	-0.026	0.044	1000	-1000	-0.023	-1000
IL2 signaling events mediated by STAT5	14	311	22	-0.025	0.036	1000	-1000	-0.03	-1000
Neurotrophic factor-mediated Trk receptor signaling	14	1721	120	-0.079	0.088	1000	-1000	-0.033	-1000
LPA4-mediated signaling events	13	156	12	-0.028	0.022	1000	-1000	-0.021	-1000
Sphingosine 1-phosphate (S1P) pathway	13	383	28	-0.01	0.043	1000	-1000	-0.004	-1000
Aurora A signaling	13	807	60	-0.011	0.05	1000	-1000	-0.01	-1000
Signaling mediated by p38-alpha and p38-beta	13	587	44	-0.054	0.056	1000	-1000	-0.011	-1000
Regulation of p38-alpha and p38-beta	13	703	54	-0.018	0.072	1000	-1000	-0.02	-1000
Glypican 2 network	13	54	4	0	0.013	1000	-1000	0	-1000
p38 MAPK signaling pathway	13	581	44	-0.05	0.058	1000	-1000	-0.017	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	12	1092	85	-0.14	0.064	1000	-1000	-0.042	-1000
Retinoic acid receptors-mediated signaling	12	745	58	-0.071	0.067	1000	-1000	-0.025	-1000
Atypical NF-kappaB pathway	12	385	31	-0.018	0.035	1000	-1000	-0.013	-1000
S1P4 pathway	12	301	25	-0.009	0.043	1000	-1000	-0.013	-1000
S1P5 pathway	11	191	17	-0.001	0.035	1000	-1000	-0.005	-1000
Effects of Botulinum toxin	11	300	26	-0.064	0.051	1000	-1000	0	-1000
S1P3 pathway	11	497	42	-0.017	0.043	1000	-1000	-0.032	-1000
Angiopoietin receptor Tie2-mediated signaling	11	1026	88	-0.063	0.064	1000	-1000	-0.056	-1000
Nephrin/Neph1 signaling in the kidney podocyte	10	357	34	-0.039	0.075	1000	-1000	-0.032	-1000
BARD1 signaling events	10	584	57	-0.047	0.069	1000	-1000	-0.043	-1000
Paxillin-independent events mediated by a4b1 and a4b7	10	397	37	-0.024	0.073	1000	-1000	-0.024	-1000
Signaling events mediated by HDAC Class III	10	410	40	-0.063	0.064	1000	-1000	-0.038	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	10	841	83	-0.057	0.069	1000	-1000	-0.017	-1000
Paxillin-dependent events mediated by a4b1	10	370	36	-0.061	0.064	1000	-1000	-0.03	-1000
TCGA08_rtk_signaling	10	277	26	-0.026	0.042	1000	-1000	-0.008	-1000
Signaling events mediated by HDAC Class II	9	683	75	-0.088	0.076	1000	-1000	-0.024	-1000
a4b1 and a4b7 Integrin signaling	9	47	5	0.021	0.041	1000	-1000	0.022	-1000
Class I PI3K signaling events mediated by Akt	9	652	68	-0.053	0.075	1000	-1000	-0.011	-1000
Signaling events mediated by PRL	9	327	34	-0.037	0.05	1000	-1000	-0.033	-1000
Class IB PI3K non-lipid kinase events	9	27	3	-0.025	0.025	1000	-1000	-0.026	-1000
JNK signaling in the CD4+ TCR pathway	8	136	17	-0.01	0.078	1000	-1000	-0.015	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	8	285	33	-0.016	0.071	1000	-1000	-0.024	-1000
Insulin-mediated glucose transport	7	239	32	0	0.043	1000	-1000	-0.008	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	6	142	23	-0.001	0.054	1000	-1000	-0.012	-1000
Ephrin A reverse signaling	6	43	7	0	0.041	1000	-1000	0	-1000
Arf6 trafficking events	5	418	71	-0.04	0.042	1000	-1000	-0.025	-1000
Alternative NF-kappaB pathway	5	74	13	0	0.082	1000	-1000	0	-1000
Canonical NF-kappaB pathway	4	156	39	0	0.074	1000	-1000	-0.021	-1000
Circadian rhythm pathway	4	100	22	-0.01	0.067	1000	-1000	-0.04	-1000
Aurora C signaling	3	24	7	0	0.052	1000	-1000	-0.009	-1000
Signaling events mediated by HDAC Class I	3	354	104	-0.046	0.08	1000	-1000	-0.026	-1000
Arf1 pathway	3	196	54	-0.001	0.06	1000	-1000	-0.013	-1000
Rapid glucocorticoid signaling	2	56	20	-0.002	0.044	1000	-1000	0	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0	26	27	0	0.08	1000	-1000	-0.02	-1000
Total	3378	209364	7203	-11	8	131000	-131000	-3.4	-131000

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.038	0.13	-10000	0	-0.53	29	29
Crk/p130 Cas/Paxillin	-0.13	0.16	-10000	0	-0.33	165	165
JUN	-0.13	0.18	0.19	2	-0.4	116	118
HRAS	0.032	0.036	-10000	0	-0.42	3	3
RET51/GFRalpha1/GDNF/GRB10	-0.1	0.2	-10000	0	-0.31	228	228
RAP1A	0.03	0.05	-10000	0	-0.42	6	6
FRS2	0.033	0.022	-10000	0	-0.42	1	1
RAP1A/GDP	0.022	0.035	-10000	0	-0.3	6	6
RET51/GFRalpha1/GDNF/DOK1	-0.099	0.21	-10000	0	-0.32	221	221
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.036	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.031	0.023	-10000	0	-0.42	1	1
RET9/GFRalpha1/GDNF/Enigma	-0.041	0.14	-10000	0	-0.23	170	170
RHOA	0.026	0.061	-10000	0	-0.42	9	9
RAP1A/GTP	-0.095	0.18	-10000	0	-0.28	223	223
GRB7	0.024	0.058	-10000	0	-0.42	8	8
RET51/GFRalpha1/GDNF	-0.094	0.2	-10000	0	-0.31	218	218
MAPKKK cascade	-0.11	0.19	-10000	0	-0.33	203	203
BCAR1	0.029	0.014	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.064	0.17	-10000	0	-0.28	180	180
lamellipodium assembly	-0.11	0.16	-10000	0	-0.31	164	164
RET51/GFRalpha1/GDNF/SHC	-0.082	0.18	-10000	0	-0.3	195	195
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
RET9/GFRalpha1/GDNF/SHC	-0.029	0.12	-10000	0	-0.24	122	122
RET9/GFRalpha1/GDNF/Shank3	-0.043	0.14	-10000	0	-0.24	173	173
MAPK3	-0.12	0.16	0.34	1	-0.38	91	92
DOK1	0.027	0.061	-10000	0	-0.42	9	9
DOK6	0.006	0.11	-10000	0	-0.42	30	30
PXN	0.036	0.004	-10000	0	-10000	0	0
neurite development	-0.11	0.16	0.28	2	-0.37	101	103
DOK5	0.014	0.083	-10000	0	-0.42	17	17
GFRA1	-0.13	0.21	-10000	0	-0.42	177	177
MAPK8	-0.12	0.18	-10000	0	-0.3	222	222
HRAS/GTP	-0.12	0.22	-10000	0	-0.35	217	217
tube development	-0.031	0.14	0.22	24	-0.22	162	186
MAPK1	-0.12	0.16	0.34	1	-0.38	91	92
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.054	0.12	-10000	0	-0.22	156	156
Rac1/GDP	0.026	0.004	-10000	0	-10000	0	0
SRC	0.032	0.03	-10000	0	-0.42	2	2
PDLIM7	0.035	0.007	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.095	0.21	-10000	0	-0.32	219	219
SHC1	0.027	0.025	-10000	0	-0.42	1	1
RET51/GFRalpha1/GDNF/Dok4	-0.1	0.2	-10000	0	-0.31	221	221
RET51/GFRalpha1/GDNF/Dok5	-0.1	0.2	-10000	0	-0.32	212	212
PRKCA	0.031	0.012	-10000	0	-10000	0	0
HRAS/GDP	0.024	0.025	-10000	0	-0.3	3	3
CREB1	-0.087	0.17	-10000	0	-0.33	148	148
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.039	0.11	-10000	0	-0.23	114	114
RET51/GFRalpha1/GDNF/Grb7	-0.097	0.2	-10000	0	-0.32	213	213
mol:GDP	0	0	-10000	0	-10000	0	0
RET	-0.096	0.2	-10000	0	-0.42	138	138
DOK4	0.028	0.032	-10000	0	-0.42	2	2
JNK cascade	-0.13	0.17	0.19	2	-0.39	116	118
RET9/GFRalpha1/GDNF/FRS2	-0.043	0.14	-10000	0	-0.24	168	168
SHANK3	0.034	0.029	-10000	0	-0.42	2	2
RASA1	0.028	0.054	-10000	0	-0.42	7	7
NCK1	0.034	0.022	-10000	0	-0.42	1	1
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.037	0.1	-10000	0	-0.22	113	113
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.11	0.18	-10000	0	-0.3	205	205
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.12	0.19	-10000	0	-0.32	220	220
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.11	0.2	-10000	0	-0.34	180	180
PI3K	-0.16	0.25	-10000	0	-0.47	167	167
SOS1	0.034	0.021	-10000	0	-0.42	1	1
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.029	0.14	-10000	0	-0.22	162	162
GRB10	0.022	0.075	-10000	0	-0.42	14	14
activation of MAPKK activity	-0.082	0.15	-10000	0	-0.33	94	94
RET51/GFRalpha1/GDNF/FRS2	-0.097	0.2	-10000	0	-0.32	217	217
GAB1	0.027	0.061	-10000	0	-0.42	9	9
IRS1	-0.014	0.14	-10000	0	-0.42	54	54
IRS2	0.008	0.099	-10000	0	-0.42	25	25
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.12	0.2	-10000	0	-0.35	186	186
RET51/GFRalpha1/GDNF/PKC alpha	-0.091	0.2	-10000	0	-0.32	201	201
GRB2	0.033	0.01	-10000	0	-10000	0	0
PRKACA	0.036	0.004	-10000	0	-10000	0	0
GDNF	0.032	0.036	-10000	0	-0.42	3	3
RAC1	0.035	0.006	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.12	0.23	-10000	0	-0.35	226	226
Rac1/GTP	-0.12	0.2	-10000	0	-0.37	163	163
RET9/GFRalpha1/GDNF	-0.061	0.14	-10000	0	-0.26	171	171
GFRalpha1/GDNF	-0.075	0.17	-10000	0	-0.3	171	171

×

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	-0.12	0.2	0.38	1	-0.41	131	132
CRKL	-0.13	0.2	-10000	0	-0.43	135	135
HRAS	-0.077	0.17	-10000	0	-0.36	91	91
mol:PIP3	-0.087	0.2	0.28	2	-0.42	100	102
SPRED1	0.02	0.08	-10000	0	-0.42	16	16
SPRED2	0.02	0.083	-10000	0	-0.42	17	17
GAB1	-0.14	0.21	-10000	0	-0.45	136	136
FOXO3	-0.1	0.2	-10000	0	-0.39	131	131
AKT1	-0.11	0.22	-10000	0	-0.42	130	130
BAD	-0.1	0.2	-10000	0	-0.39	129	129
megakaryocyte differentiation	-0.13	0.21	-10000	0	-0.44	133	133
GSK3B	-0.1	0.2	0.34	1	-0.39	128	129
RAF1	-0.054	0.15	0.25	9	-0.31	82	91
SHC1	0.027	0.025	-10000	0	-0.42	1	1
STAT3	-0.12	0.21	-10000	0	-0.43	132	132
STAT1	-0.31	0.48	-10000	0	-0.89	183	183
HRAS/SPRED1	-0.055	0.16	0.26	2	-0.32	86	88
cell proliferation	-0.13	0.21	-10000	0	-0.44	134	134
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
TEC	0.031	0.046	-10000	0	-0.42	5	5
RPS6KB1	-0.12	0.22	-10000	0	-0.45	133	133
HRAS/SPRED2	-0.053	0.16	0.26	2	-0.31	88	90
LYN/TEC/p62DOK	-0.093	0.22	-10000	0	-0.42	126	126
MAPK3	-0.033	0.12	0.24	13	-0.25	37	50
STAP1	-0.13	0.21	-10000	0	-0.44	133	133
GRAP2	0.032	0.023	-10000	0	-0.42	1	1
JAK2	-0.26	0.41	-10000	0	-0.76	176	176
STAT1 (dimer)	-0.3	0.46	-10000	0	-0.86	184	184
mol:Gleevec	0.005	0.008	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.099	0.22	-10000	0	-0.42	123	123
actin filament polymerization	-0.13	0.21	-10000	0	-0.44	133	133
LYN	0.03	0.014	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.19	0.3	-10000	0	-0.58	160	160
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
CBL/CRKL/GRB2	-0.1	0.2	-10000	0	-0.4	125	125
PI3K	-0.1	0.23	-10000	0	-0.45	123	123
PTEN	0.027	0.061	-10000	0	-0.42	9	9
SCF/KIT/EPO/EPOR	-0.3	0.53	-10000	0	-1.2	122	122
MAPK8	-0.13	0.21	-10000	0	-0.44	134	134
STAT3 (dimer)	-0.12	0.2	-10000	0	-0.43	132	132
positive regulation of transcription	-0.024	0.1	0.22	13	-0.21	30	43
mol:GDP	-0.084	0.17	-10000	0	-0.38	90	90
PIK3C2B	-0.12	0.2	0.28	1	-0.42	127	128
CBL/CRKL	-0.12	0.2	-10000	0	-0.41	133	133
FER	-0.13	0.21	-10000	0	-0.45	132	132
SH2B3	-0.13	0.21	-10000	0	-0.44	133	133
PDPK1	-0.069	0.2	0.3	14	-0.38	93	107
SNAI2	-0.14	0.22	-10000	0	-0.46	136	136
positive regulation of cell proliferation	-0.22	0.36	-10000	0	-0.7	160	160
KITLG	-0.052	0.16	-10000	0	-0.45	72	72
cell motility	-0.22	0.36	-10000	0	-0.7	160	160
PTPN6	0.038	0.032	-10000	0	-0.41	2	2
EPOR	-0.068	0.18	-10000	0	-1	5	5
STAT5A (dimer)	-0.19	0.3	-10000	0	-0.59	156	156
SOCS1	0.031	0.023	-10000	0	-0.42	1	1
cell migration	0.13	0.21	0.44	133	-10000	0	133
SOS1	0.034	0.021	-10000	0	-0.42	1	1
EPO	0.012	0.029	-10000	0	-10000	0	0
VAV1	0.018	0.083	-10000	0	-0.42	17	17
GRB10	-0.14	0.21	-10000	0	-0.45	133	133
PTPN11	0.04	0.009	-10000	0	-10000	0	0
SCF/KIT	-0.14	0.22	-10000	0	-0.47	133	133
GO:0007205	0.007	0.011	-10000	0	-10000	0	0
MAP2K1	-0.04	0.13	0.25	12	-0.25	72	84
CBL	0.031	0.012	-10000	0	-10000	0	0
KIT	-0.27	0.53	-10000	0	-1.3	101	101
MAP2K2	-0.042	0.13	0.26	11	-0.25	74	85
SHC/Grb2/SOS1	-0.08	0.2	-10000	0	-0.42	94	94
STAT5A	-0.2	0.32	-10000	0	-0.61	156	156
GRB2	0.033	0.01	-10000	0	-10000	0	0
response to radiation	-0.14	0.22	-10000	0	-0.45	137	137
SHC/GRAP2	0.038	0.032	-10000	0	-0.3	2	2
PTPRO	-0.14	0.21	-10000	0	-0.46	132	132
SH2B2	-0.13	0.21	-10000	0	-0.44	133	133
DOK1	0.027	0.061	-10000	0	-0.42	9	9
MATK	-0.13	0.21	-10000	0	-0.45	133	133
CREBBP	-0.009	0.08	-10000	0	-0.18	16	16
BCL2	-0.3	0.56	-10000	0	-1.3	113	113

×

Endothelins

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.013	0.2	0.27	74	-0.32	104	178
PTK2B	0.028	0.015	-10000	0	-10000	0	0
mol:Ca2+	-0.057	0.26	-10000	0	-0.68	49	49
EDN1	-0.01	0.19	0.23	68	-0.43	68	136
EDN3	-0.014	0.12	-10000	0	-0.42	40	40
EDN2	-0.055	0.18	-10000	0	-0.42	94	94
HRAS/GDP	-0.065	0.24	0.28	5	-0.48	90	95
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.06	0.2	-10000	0	-0.41	94	94
ADCY4	-0.013	0.17	0.25	9	-0.39	49	58
ADCY5	-0.016	0.16	0.24	2	-0.41	42	44
ADCY6	-0.012	0.16	0.24	7	-0.4	44	51
ADCY7	-0.015	0.16	0.26	3	-0.4	40	43
ADCY1	-0.011	0.16	0.26	6	-0.39	43	49
ADCY2	-0.029	0.18	0.24	5	-0.42	55	60
ADCY3	-0.013	0.16	0.25	9	-0.39	47	56
ADCY8	-0.007	0.14	0.26	4	-0.37	37	41
ADCY9	-0.016	0.16	0.24	7	-0.38	47	54
arachidonic acid secretion	-0.089	0.25	0.27	1	-0.51	109	110
ETB receptor/Endothelin-1/Gq/GTP	-0.051	0.16	-10000	0	-0.32	104	104
GNAO1	0.03	0.014	-10000	0	-10000	0	0
HRAS	0.031	0.036	-10000	0	-0.42	3	3
ETA receptor/Endothelin-1/G12/GTP	0.03	0.22	0.37	75	-0.3	102	177
ETA receptor/Endothelin-1/Gs/GTP	0.024	0.2	0.35	74	-0.29	96	170
mol:GTP	-0.001	0.006	-10000	0	-10000	0	0
COL3A1	-0.019	0.22	0.27	73	-0.54	43	116
EDNRB	0.002	0.099	-10000	0	-0.37	26	26
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.01	0.2	0.27	72	-0.4	65	137
CYSLTR1	-0.029	0.23	0.27	75	-0.44	85	160
SLC9A1	-0.006	0.13	0.19	74	-0.3	41	115
mol:GDP	-0.081	0.24	0.27	5	-0.5	95	100
SLC9A3	-0.12	0.35	-10000	0	-0.71	108	108
RAF1	-0.095	0.24	-10000	0	-0.49	109	109
JUN	-0.099	0.35	-10000	0	-0.95	62	62
JAK2	-0.011	0.19	0.27	74	-0.33	97	171
mol:IP3	-0.073	0.21	0.23	1	-0.44	94	95
ETA receptor/Endothelin-1	0.014	0.26	0.42	75	-0.38	107	182
PLCB1	-0.021	0.14	-10000	0	-0.42	56	56
PLCB2	0.032	0.023	-10000	0	-0.43	1	1
ETA receptor/Endothelin-3	-0.004	0.15	-10000	0	-0.33	76	76
FOS	-0.14	0.36	-10000	0	-0.92	79	79
Gai/GDP	-0.11	0.32	-10000	0	-0.75	93	93
CRK	0.031	0.023	-10000	0	-0.42	1	1
mol:Ca ++	-0.089	0.27	0.26	6	-0.52	106	112
BCAR1	0.029	0.014	-10000	0	-10000	0	0
PRKCB1	-0.076	0.22	0.26	14	-0.46	92	106
GNAQ	-0.001	0.007	-10000	0	-10000	0	0
GNAZ	0.024	0.067	-10000	0	-0.42	11	11
GNAL	0.031	0.036	-10000	0	-0.42	3	3
Gs family/GDP	-0.065	0.22	0.26	4	-0.46	90	94
ETA receptor/Endothelin-1/Gq/GTP	-0.043	0.2	0.2	67	-0.39	92	159
MAPK14	-0.068	0.17	0.22	1	-0.39	79	80
TRPC6	-0.062	0.27	-10000	0	-0.73	49	49
GNAI2	0.027	0.057	-10000	0	-0.42	8	8
GNAI3	0.035	0.006	-10000	0	-10000	0	0
GNAI1	0.017	0.085	-10000	0	-0.42	18	18
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.067	0.18	-10000	0	-0.38	94	94
ETB receptor/Endothelin-2	-0.041	0.15	-10000	0	-0.31	113	113
ETB receptor/Endothelin-3	-0.011	0.11	-10000	0	-0.31	56	56
ETB receptor/Endothelin-1	-0.012	0.17	-10000	0	-0.32	96	96
MAPK3	-0.14	0.34	-10000	0	-0.77	94	94
MAPK1	-0.14	0.34	-10000	0	-0.8	91	91
Rac1/GDP	-0.063	0.23	0.28	5	-0.49	86	91
cAMP biosynthetic process	-0.005	0.17	0.26	22	-0.4	45	67
MAPK8	-0.072	0.3	-10000	0	-0.68	71	71
SRC	0.032	0.03	-10000	0	-0.42	2	2
ETB receptor/Endothelin-1/Gi/GTP	-0.043	0.16	-10000	0	-0.35	80	80
p130Cas/CRK/Src/PYK2	-0.1	0.26	0.31	1	-0.55	97	98
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.063	0.23	0.28	5	-0.48	90	95
COL1A2	-0.074	0.3	0.39	1	-0.57	106	107
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.034	0.18	-10000	0	-0.32	128	128
mol:DAG	-0.073	0.21	0.23	1	-0.44	94	95
MAP2K2	-0.12	0.28	0.32	1	-0.6	104	105
MAP2K1	-0.11	0.28	0.29	2	-0.6	102	104
EDNRA	0.014	0.17	0.23	74	-0.37	63	137
positive regulation of muscle contraction	-0.014	0.17	0.22	74	-0.38	50	124
Gq family/GDP	-0.059	0.22	-10000	0	-0.46	83	83
HRAS/GTP	-0.081	0.23	-10000	0	-0.48	92	92
PRKCH	-0.075	0.21	0.23	4	-0.45	89	93
RAC1	0.035	0.006	-10000	0	-10000	0	0
PRKCA	-0.06	0.21	0.23	23	-0.45	81	104
PRKCB	-0.074	0.2	0.22	1	-0.42	98	99
PRKCE	-0.076	0.2	0.21	1	-0.45	85	86
PRKCD	-0.075	0.2	0.22	1	-0.45	85	86
PRKCG	-0.079	0.2	0.22	1	-0.45	87	88
regulation of vascular smooth muscle contraction	-0.18	0.42	-10000	0	-1.1	79	79
PRKCQ	-0.069	0.2	0.23	6	-0.44	86	92
PLA2G4A	-0.1	0.28	0.27	1	-0.55	109	110
GNA14	-0.014	0.13	-10000	0	-0.43	44	44
GNA15	0.026	0.048	-10000	0	-0.42	5	5
GNA12	0.035	0.006	-10000	0	-10000	0	0
GNA11	0.029	0.039	-10000	0	-0.42	3	3
Rac1/GTP	0.029	0.22	0.37	74	-0.32	84	158
MMP1	-0.17	0.35	0.25	7	-0.78	120	127

×

Osteopontin-mediated 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.038	0.15	0.36	1	-0.27	129	130
NF kappa B1 p50/RelA/I kappa B alpha	-0.035	0.17	0.33	1	-0.42	49	50
alphaV/beta3 Integrin/Osteopontin/Src	-0.046	0.17	-10000	0	-0.32	127	127
AP1	-0.086	0.23	-10000	0	-0.49	84	84
ILK	-0.048	0.14	0.38	1	-0.26	128	129
bone resorption	-0.055	0.14	0.32	1	-0.35	45	46
PTK2B	0.028	0.015	-10000	0	-10000	0	0
PYK2/p130Cas	-0.029	0.16	-10000	0	-0.26	135	135
ITGAV	0.017	0.084	-10000	0	-0.43	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.038	0.066	-10000	0	-0.3	18	18
alphaV/beta3 Integrin/Osteopontin	-0.023	0.16	-10000	0	-0.29	129	129
MAP3K1	-0.06	0.14	0.23	6	-0.27	146	152
JUN	-0.002	0.12	-10000	0	-0.42	39	39
MAPK3	-0.061	0.14	0.22	8	-0.27	132	140
MAPK1	-0.065	0.15	0.22	8	-0.28	136	144
Rac1/GDP	0.026	0.004	-10000	0	-10000	0	0
NFKB1	0.035	0.005	-10000	0	-10000	0	0
MAPK8	-0.065	0.13	0.22	9	-0.26	142	151
ITGB3	0.024	0.051	-10000	0	-0.43	5	5
NFKBIA	-0.069	0.16	0.35	2	-0.42	58	60
FOS	-0.031	0.15	-10000	0	-0.42	66	66
CD44	0.022	0.075	-10000	0	-0.42	14	14
CHUK	0.025	0.067	-10000	0	-0.42	11	11
PLAU	-0.14	0.36	-10000	0	-1.1	56	56
NF kappa B1 p50/RelA	-0.022	0.19	-10000	0	-0.45	55	55
BCAR1	0.029	0.014	-10000	0	-10000	0	0
RELA	0.035	0.006	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.03	0.082	-10000	0	-0.32	22	22
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.062	0.15	0.22	8	-0.28	149	157
VAV3	-0.1	0.15	0.22	8	-0.27	205	213
MAP3K14	-0.051	0.15	0.23	7	-0.27	131	138
ROCK2	0.032	0.041	-10000	0	-0.42	4	4
SPP1	-0.078	0.19	-10000	0	-0.43	117	117
RAC1	0.035	0.006	-10000	0	-10000	0	0
Rac1/GTP	-0.084	0.15	0.19	5	-0.25	200	205
MMP2	-0.1	0.19	-10000	0	-0.45	85	85

×

IGF1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.036	0.004	-10000	0	-10000	0	0
PTK2	0.027	0.015	-10000	0	-10000	0	0
CRKL	-0.073	0.15	0.17	2	-0.3	137	139
GRB2/SOS1/SHC	0.051	0.036	-10000	0	-0.26	1	1
HRAS	0.032	0.036	-10000	0	-0.42	3	3
IRS1/Crk	-0.066	0.16	-10000	0	-0.3	143	143
IGF-1R heterotetramer/IGF1/PTP1B	-0.037	0.16	-10000	0	-0.29	131	131
AKT1	-0.08	0.14	0.17	13	-0.38	59	72
BAD	-0.078	0.13	0.15	13	-0.37	56	69
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.069	0.15	0.17	2	-0.3	131	133
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.062	0.16	0.22	1	-0.3	143	144
RAF1	-0.041	0.14	0.29	3	-0.49	15	18
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.028	0.17	-10000	0	-0.29	130	130
YWHAZ	0.026	0.016	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.065	0.17	-10000	0	-0.31	153	153
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
RPS6KB1	-0.073	0.13	0.17	12	-0.38	55	67
GNB2L1	0.033	0.035	-10000	0	-0.42	3	3
positive regulation of MAPKKK cascade	-0.027	0.14	0.31	8	-0.42	13	21
PXN	0.036	0.004	-10000	0	-10000	0	0
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.047	0.023	-10000	0	-0.3	1	1
HRAS/GTP	-0.042	0.13	-10000	0	-0.27	114	114
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.001	0.14	-10000	0	-0.24	104	104
IGF-1R heterotetramer	-0.062	0.18	-10000	0	-0.47	84	84
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.045	0.17	-10000	0	-0.3	143	143
Crk/p130 Cas/Paxillin	-0.041	0.16	-10000	0	-0.28	139	139
IGF1R	-0.062	0.18	-10000	0	-0.47	84	84
IGF1	-0.062	0.18	-10000	0	-0.46	80	80
IRS2/Crk	-0.072	0.16	0.17	2	-0.3	151	153
PI3K	-0.04	0.18	-10000	0	-0.29	147	147
apoptosis	0.052	0.12	0.32	46	-0.29	5	51
HRAS/GDP	0.024	0.025	-10000	0	-0.3	3	3
PRKCD	-0.066	0.18	-10000	0	-0.34	130	130
RAF1/14-3-3 E	-0.021	0.14	0.29	3	-0.42	15	18
BAD/14-3-3	-0.054	0.12	0.3	5	-0.34	46	51
PRKCZ	-0.078	0.14	0.16	13	-0.28	130	143
Crk/p130 Cas/Paxillin/FAK1	-0.032	0.13	-10000	0	-0.35	44	44
PTPN1	0.03	0.031	-10000	0	-0.42	2	2
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.078	0.18	-10000	0	-0.35	132	132
BCAR1	0.029	0.014	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.02	0.15	-10000	0	-0.26	123	123
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.034	0.021	-10000	0	-0.42	1	1
IRS1/NCK2	-0.056	0.16	-10000	0	-0.29	143	143
GRB10	0.022	0.075	-10000	0	-0.42	14	14
PTPN11	-0.074	0.15	0.17	2	-0.3	143	145
IRS1	-0.077	0.16	-10000	0	-0.31	153	153
IRS2	-0.08	0.16	0.17	2	-0.31	143	145
IGF-1R heterotetramer/IGF1	-0.074	0.19	-10000	0	-0.37	141	141
GRB2	0.033	0.01	-10000	0	-10000	0	0
PDPK1	-0.077	0.14	0.18	13	-0.29	127	140
YWHAE	0.032	0.011	-10000	0	-10000	0	0
PRKD1	-0.075	0.2	0.21	5	-0.37	129	134
SHC1	0.027	0.025	-10000	0	-0.42	1	1

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.36	0.64	-10000	0	-1.3	130	130
STAT6 (cleaved dimer)	-0.38	0.65	-10000	0	-1.3	140	140
IGHG1	-0.082	0.24	-10000	0	-0.56	27	27
IGHG3	-0.35	0.61	-10000	0	-1.2	143	143
AKT1	-0.12	0.33	-10000	0	-0.77	51	51
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.066	0.26	-10000	0	-0.77	28	28
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.14	0.36	-10000	0	-0.83	60	60
THY1	-0.37	0.66	-10000	0	-1.3	133	133
MYB	-0.056	0.18	-10000	0	-0.42	98	98
HMGA1	0.033	0.029	-10000	0	-0.42	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.14	0.34	-10000	0	-0.66	95	95
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.12	0.33	-10000	0	-0.86	39	39
SP1	0.024	0.051	-10000	0	-0.2	6	6
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.019	0.056	-10000	0	-0.42	4	4
STAT6 (dimer)/ETS1	-0.37	0.64	-10000	0	-1.3	138	138
SOCS1	-0.2	0.38	-10000	0	-0.74	133	133
SOCS3	-0.12	0.32	-10000	0	-0.97	23	23
FCER2	-0.23	0.46	-10000	0	-0.93	101	101
PARP14	0.03	0.051	-10000	0	-0.42	6	6
CCL17	-0.42	0.71	-10000	0	-1.4	155	155
GRB2	0.033	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.075	0.26	-10000	0	-0.68	33	33
T cell proliferation	-0.37	0.67	-10000	0	-1.3	139	139
IL4R/JAK1	-0.37	0.65	-10000	0	-1.3	135	135
EGR2	-0.41	0.7	-10000	0	-1.4	145	145
JAK2	-0.005	0.069	-10000	0	-0.46	2	2
JAK3	0.038	0.014	-10000	0	-10000	0	0
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
JAK1	0.018	0.049	-10000	0	-0.42	3	3
COL1A2	-0.22	0.53	-10000	0	-1.5	70	70
CCL26	-0.37	0.64	-10000	0	-1.3	139	139
IL4R	-0.39	0.71	-10000	0	-1.4	136	136
PTPN6	0.021	0.045	-10000	0	-0.41	2	2
IL13RA2	-0.4	0.67	-10000	0	-1.3	152	152
IL13RA1	-0.009	0.087	-10000	0	-0.46	8	8
IRF4	-0.005	0.16	-10000	0	-1	5	5
ARG1	-0.065	0.26	-10000	0	-1.1	17	17
CBL	-0.14	0.32	-10000	0	-0.63	93	93
GTF3A	0.024	0.045	-10000	0	-0.14	6	6
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
IL13RA1/JAK2	-0.002	0.1	-10000	0	-0.37	8	8
IRF4/BCL6	-0.005	0.16	-10000	0	-0.97	5	5
CD40LG	0.038	0.038	-10000	0	-0.42	3	3
MAPK14	-0.14	0.33	-10000	0	-0.67	79	79
mitosis	-0.11	0.31	-10000	0	-0.72	51	51
STAT6	-0.47	0.88	-10000	0	-1.7	142	142
SPI1	0.032	0.055	-10000	0	-0.26	14	14
RPS6KB1	-0.092	0.3	-10000	0	-0.72	43	43
STAT6 (dimer)	-0.47	0.88	-10000	0	-1.7	142	142
STAT6 (dimer)/PARP14	-0.41	0.73	-10000	0	-1.4	141	141
mast cell activation	0.005	0.017	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.14	0.34	-10000	0	-0.75	70	70
FRAP1	-0.12	0.33	-10000	0	-0.77	51	51
LTA	-0.36	0.64	-10000	0	-1.3	136	136
FES	0.03	0.041	-10000	0	-0.42	4	4
T-helper 1 cell differentiation	0.43	0.78	1.5	142	-10000	0	142
CCL11	-0.4	0.66	-10000	0	-1.3	148	148
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.1	0.31	0.5	1	-0.83	34	35
IL2RG	0.033	0.043	-10000	0	-0.41	4	4
IL10	-0.33	0.65	-10000	0	-1.3	118	118
IRS1	-0.014	0.14	-10000	0	-0.42	54	54
IRS2	0.008	0.099	-10000	0	-0.42	25	25
IL4	-0.064	0.29	-10000	0	-1.3	19	19
IL5	-0.36	0.64	-10000	0	-1.3	136	136
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.26	0.51	-10000	0	-0.93	144	144
COL1A1	-0.26	0.59	-10000	0	-1.4	91	91
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.39	0.69	-10000	0	-1.4	137	137
IL2R gamma/JAK3	0.053	0.036	-10000	0	-0.29	4	4
TFF3	-0.53	0.76	-10000	0	-1.4	204	204
ALOX15	-0.37	0.65	-10000	0	-1.3	134	134
MYBL1	-0.012	0.13	-10000	0	-0.42	43	43
T-helper 2 cell differentiation	-0.28	0.52	-10000	0	-0.98	141	141
SHC1	0.027	0.025	-10000	0	-0.42	1	1
CEBPB	0.028	0.056	-10000	0	-0.32	10	10
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.13	0.33	-10000	0	-0.77	54	54
mol:PI-3-4-5-P3	-0.12	0.33	-10000	0	-0.77	51	51
PI3K	-0.13	0.35	-10000	0	-0.84	51	51
DOK2	0.01	0.085	-10000	0	-0.42	18	18
ETS1	0.014	0.044	-10000	0	-0.38	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.061	0.25	-10000	0	-0.62	30	30
ITGB3	-0.37	0.64	-10000	0	-1.3	134	134
PIGR	-0.46	0.77	-10000	0	-1.4	174	174
IGHE	0.012	0.089	0.19	48	-0.22	10	58
MAPKKK cascade	-0.059	0.24	-10000	0	-0.61	30	30
BCL6	0.017	0.085	-10000	0	-0.42	18	18
OPRM1	-0.36	0.64	-10000	0	-1.3	135	135
RETNLB	-0.36	0.64	-10000	0	-1.3	136	136
SELP	-0.42	0.75	-10000	0	-1.4	158	158
AICDA	-0.36	0.62	-10000	0	-1.2	138	138

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.24	0.51	-9999	-1.2	82	82
PLK1	0.017	0.098	-9999	-1.1	3	3
BIRC5	-0.086	0.39	-9999	-1.4	41	41
HSPA1B	-0.24	0.51	-9999	-1.1	96	96
MAP2K1	0.005	0.057	-9999	-10000	0	0
BRCA2	-0.26	0.54	-9999	-1.2	92	92
FOXM1	-0.38	0.86	-9999	-1.8	94	94
XRCC1	-0.24	0.51	-9999	-1.2	83	83
FOXM1B/p19	-0.29	0.57	-9999	-1.3	93	93
Cyclin D1/CDK4	-0.29	0.52	-9999	-1	134	134
CDC2	-0.26	0.56	-9999	-1.3	84	84
TGFA	-0.28	0.5	-9999	-1	112	112
SKP2	-0.24	0.51	-9999	-1.2	78	78
CCNE1	0.023	0.05	-9999	-0.44	5	5
CKS1B	-0.21	0.52	-9999	-1.2	81	81
RB1	-0.15	0.39	-9999	-1	63	63
FOXM1C/SP1	-0.29	0.62	-9999	-1.4	97	97
AURKB	-0.083	0.32	-9999	-1	45	45
CENPF	-0.23	0.56	-9999	-1.3	77	77
CDK4	0.015	0.038	-9999	-10000	0	0
MYC	-0.23	0.44	-9999	-1	89	89
CHEK2	0.001	0.066	-9999	-0.45	3	3
ONECUT1	-0.27	0.52	-9999	-1.1	101	101
CDKN2A	0.014	0.075	-9999	-0.42	14	14
LAMA4	-0.24	0.52	-9999	-1.2	83	83
FOXM1B/HNF6	-0.34	0.65	-9999	-1.4	101	101
FOS	-0.33	0.6	-9999	-1.2	131	131
SP1	0.033	0.024	-9999	-0.42	1	1
CDC25B	-0.24	0.52	-9999	-1.2	83	83
response to radiation	-0.004	0.031	-9999	-10000	0	0
CENPB	-0.24	0.51	-9999	-1.2	79	79
CENPA	-0.26	0.54	-9999	-1.2	86	86
NEK2	-0.26	0.58	-9999	-1.2	100	100
HIST1H2BA	-0.24	0.52	-9999	-1.2	85	85
CCNA2	0.004	0.11	-9999	-0.44	28	28
EP300	0.033	0.022	-9999	-0.42	1	1
CCNB1/CDK1	-0.31	0.64	-9999	-1.5	85	85
CCNB2	-0.25	0.53	-9999	-1.2	85	85
CCNB1	-0.27	0.56	-9999	-1.3	85	85
ETV5	-0.24	0.52	-9999	-1.2	79	79
ESR1	-0.43	0.65	-9999	-1.2	203	203
CCND1	-0.32	0.52	-9999	-1.1	135	135
GSK3A	0.008	0.052	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.022	0.11	-9999	-0.33	29	29
CDK2	0.028	0.035	-9999	-0.43	2	2
G2/M transition of mitotic cell cycle	-0.006	0.036	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.27	0.57	-9999	-1.3	93	93
GAS1	-0.32	0.59	-9999	-1.2	119	119
MMP2	-0.27	0.56	-9999	-1.3	94	94
RB1/FOXM1C	-0.29	0.55	-9999	-1.1	110	110
CREBBP	0.032	0.011	-9999	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.007	0.13	-10000	0	-0.22	132	132
ER alpha/Gai/GDP/Gbeta gamma	-0.12	0.21	-10000	0	-0.37	158	158
AKT1	-0.22	0.37	-10000	0	-0.74	164	164
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.22	0.37	-10000	0	-0.75	164	164
mol:Ca2+	-0.07	0.15	0.17	1	-0.43	58	59
IGF1R	-0.043	0.17	-10000	0	-0.42	84	84
E2/ER alpha (dimer)/Striatin	-0.037	0.13	-10000	0	-0.25	133	133
SHC1	0.027	0.025	-10000	0	-0.42	1	1
apoptosis	0.21	0.35	0.7	164	-10000	0	164
RhoA/GTP	-0.039	0.11	-10000	0	-0.22	129	129
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.1	0.21	-10000	0	-0.38	150	150
regulation of stress fiber formation	0.041	0.1	0.33	7	-0.26	3	10
E2/ERA-ERB (dimer)	-0.037	0.13	-10000	0	-0.25	130	130
KRAS	0.027	0.057	-10000	0	-0.42	8	8
G13/GTP	-0.033	0.12	-10000	0	-0.23	124	124
pseudopodium formation	-0.041	0.1	0.26	3	-0.33	7	10
E2/ER alpha (dimer)/PELP1	-0.038	0.13	-10000	0	-0.25	129	129
GRB2	0.033	0.01	-10000	0	-10000	0	0
GNG2	0.034	0.021	-10000	0	-0.42	1	1
GNAO1	0.03	0.014	-10000	0	-10000	0	0
HRAS	0.032	0.036	-10000	0	-0.42	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.14	0.24	0.24	1	-0.44	165	166
E2/ER beta (dimer)	0.025	0.006	-10000	0	-10000	0	0
mol:GDP	-0.075	0.17	-10000	0	-0.34	136	136
mol:NADP	-0.14	0.24	0.24	1	-0.44	165	166
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
mol:IP3	-0.073	0.15	-10000	0	-0.44	58	58
IGF-1R heterotetramer	-0.043	0.17	-10000	0	-0.42	84	84
PLCB1	-0.071	0.16	-10000	0	-0.45	58	58
PLCB2	-0.052	0.15	-10000	0	-0.45	52	52
IGF1	-0.041	0.17	-10000	0	-0.42	80	80
mol:L-citrulline	-0.14	0.24	0.24	1	-0.44	165	166
RHOA	0.026	0.061	-10000	0	-0.42	9	9
Gai/GDP	-0.1	0.28	-10000	0	-0.63	100	100
JNK cascade	0.025	0.006	-10000	0	-10000	0	0
BCAR1	0.029	0.014	-10000	0	-10000	0	0
ESR2	0.034	0.008	-10000	0	-10000	0	0
GNAQ	0	0	-10000	0	-10000	0	0
ESR1	-0.088	0.2	-10000	0	-0.42	130	130
Gq family/GDP/Gbeta gamma	-0.019	0.17	-10000	0	-0.67	23	23
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.034	0.13	-10000	0	-0.57	7	7
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.089	0.19	-10000	0	-0.38	122	122
GNAZ	0.024	0.067	-10000	0	-0.42	11	11
E2/ER alpha (dimer)	-0.061	0.14	-10000	0	-0.3	130	130
STRN	0.031	0.046	-10000	0	-0.42	5	5
GNAL	0.031	0.036	-10000	0	-0.42	3	3
PELP1	0.032	0.011	-10000	0	-10000	0	0
MAPK11	0.016	0.006	-10000	0	-10000	0	0
GNAI2	0.027	0.057	-10000	0	-0.42	8	8
GNAI3	0.035	0.006	-10000	0	-10000	0	0
GNAI1	0.017	0.085	-10000	0	-0.42	18	18
HBEGF	-0.11	0.21	0.32	8	-0.48	64	72
cAMP biosynthetic process	-0.028	0.1	-10000	0	-0.21	127	127
SRC	-0.11	0.2	0.26	2	-0.35	157	159
PI3K	0.035	0.067	-10000	0	-0.3	18	18
GNB1	0.032	0.045	-10000	0	-0.42	5	5
G13/GDP/Gbeta gamma	-0.05	0.17	-10000	0	-0.33	116	116
SOS1	0.034	0.021	-10000	0	-0.42	1	1
IGF-1R heterotetramer/IGF1	-0.13	0.19	-10000	0	-0.4	147	147
Gs family/GTP	-0.022	0.11	-10000	0	-0.21	127	127
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.053	0.054	-10000	0	-0.23	15	15
vasodilation	-0.13	0.22	0.24	1	-0.42	165	166
mol:DAG	-0.073	0.15	-10000	0	-0.44	58	58
Gs family/GDP/Gbeta gamma	-0.065	0.15	-10000	0	-0.32	112	112
MSN	-0.044	0.11	0.26	3	-0.34	8	11
Gq family/GTP	-0.053	0.15	-10000	0	-0.44	59	59
mol:PI-3-4-5-P3	-0.21	0.36	-10000	0	-0.72	164	164
NRAS	0.029	0.05	-10000	0	-0.42	6	6
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.13	0.22	0.42	165	-0.24	1	166
GRB2/SOS1	0.047	0.023	-10000	0	-0.3	1	1
RhoA/GDP	-0.061	0.17	-10000	0	-0.32	142	142
NOS3	-0.14	0.25	0.25	1	-0.47	165	166
GNA11	0.032	0.036	-10000	0	-0.42	3	3
MAPKKK cascade	-0.14	0.27	-10000	0	-0.52	157	157
E2/ER alpha (dimer)/PELP1/Src	-0.11	0.21	0.25	1	-0.39	153	154
ruffle organization	-0.041	0.1	0.26	3	-0.33	7	10
ROCK2	-0.041	0.12	0.33	2	-0.36	8	10
GNA14	-0.01	0.13	-10000	0	-0.42	44	44
GNA15	0.029	0.046	-10000	0	-0.42	5	5
GNA13	0.028	0.042	-10000	0	-0.42	4	4
MMP9	-0.12	0.21	0.37	10	-0.48	65	75
MMP2	-0.11	0.2	0.26	3	-0.47	63	66

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.034	0.034	-10000	0	-0.26	4	4
NFATC2	-0.051	0.21	-10000	0	-0.52	47	47
NFATC3	-0.018	0.12	-10000	0	-0.26	73	73
CD40LG	-0.19	0.38	-10000	0	-0.76	128	128
ITCH	0.012	0.071	-10000	0	-10000	0	0
CBLB	0.013	0.074	-10000	0	-0.22	42	42
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.14	0.33	-10000	0	-0.82	67	67
JUNB	0.032	0.041	-10000	0	-0.42	4	4
CaM/Ca2+/Calcineurin A alpha-beta B1	0.021	0.087	-10000	0	-0.26	45	45
T cell anergy	-0.016	0.12	0.26	2	-0.36	45	47
TLE4	-0.044	0.17	-10000	0	-0.49	41	41
Jun/NFAT1-c-4/p21SNFT	-0.17	0.39	-10000	0	-0.79	119	119
AP-1/NFAT1-c-4	-0.19	0.45	-10000	0	-0.86	127	127
IKZF1	-0.038	0.14	-10000	0	-0.36	47	47
T-helper 2 cell differentiation	-0.17	0.3	-10000	0	-0.74	79	79
AP-1/NFAT1	-0.045	0.2	-10000	0	-0.4	81	81
CALM1	0.027	0.058	-10000	0	-0.16	43	43
EGR2	-0.22	0.48	-10000	0	-1.2	79	79
EGR3	-0.29	0.55	-10000	0	-1.1	138	138
NFAT1/FOXP3	-0.017	0.16	-10000	0	-0.4	40	40
EGR1	-0.038	0.16	-10000	0	-0.42	75	75
JUN	-0.003	0.12	-10000	0	-0.42	39	39
EGR4	0	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.006	0.046	-10000	0	-0.15	46	46
GBP3	-0.088	0.25	-10000	0	-0.64	74	74
FOSL1	0.035	0.007	-10000	0	-10000	0	0
NFAT1-c-4/MAF/IRF4	-0.15	0.39	-10000	0	-0.77	122	122
DGKA	-0.04	0.16	-10000	0	-0.44	38	38
CREM	0.034	0.008	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.18	0.4	-10000	0	-0.8	122	122
CTLA4	-0.026	0.14	-10000	0	-0.41	28	28
NFAT1-c-4 (dimer)/EGR1	-0.19	0.42	-10000	0	-0.84	130	130
NFAT1-c-4 (dimer)/EGR4	-0.17	0.39	-10000	0	-0.78	123	123
FOS	-0.034	0.15	-10000	0	-0.42	66	66
IFNG	-0.2	0.43	-10000	0	-1.1	77	77
T cell activation	-0.1	0.26	-10000	0	-0.71	38	38
MAF	0.016	0.075	-10000	0	-0.42	14	14
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.15	0.34	0.69	115	-10000	0	115
TNF	-0.19	0.37	-10000	0	-0.76	131	131
FASLG	-0.34	0.64	-10000	0	-1.2	155	155
TBX21	-0.046	0.17	-10000	0	-0.4	92	92
BATF3	0	0.001	-10000	0	-10000	0	0
PRKCQ	0.021	0.061	-10000	0	-0.29	13	13
PTPN1	-0.037	0.15	-10000	0	-0.41	38	38
NFAT1-c-4/ICER1	-0.16	0.39	-10000	0	-0.78	121	121
GATA3	-0.047	0.18	-10000	0	-0.42	90	90
T-helper 1 cell differentiation	-0.19	0.41	-10000	0	-1	78	78
IL2RA	-0.14	0.33	-10000	0	-0.78	74	74
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.035	0.14	-10000	0	-0.44	24	24
E2F1	0.032	0.054	-10000	0	-0.42	7	7
PPARG	0.012	0.091	-10000	0	-0.42	21	21
SLC3A2	-0.035	0.14	-10000	0	-0.41	32	32
IRF4	0.031	0.031	-10000	0	-0.42	2	2
PTGS2	-0.18	0.36	-10000	0	-0.77	107	107
CSF2	-0.19	0.38	-10000	0	-0.76	129	129
JunB/Fra1/NFAT1-c-4	-0.15	0.39	-10000	0	-0.76	120	120
IL4	-0.17	0.32	-10000	0	-0.79	75	75
IL5	-0.19	0.38	-10000	0	-0.76	128	128
IL2	-0.1	0.26	-10000	0	-0.74	35	35
IL3	-0.013	0.14	-10000	0	-0.88	9	9
RNF128	-0.017	0.16	-10000	0	-0.51	45	45
NFATC1	-0.16	0.34	-10000	0	-0.7	115	115
CDK4	0.1	0.21	0.58	30	-10000	0	30
PTPRK	-0.067	0.22	-10000	0	-0.6	61	61
IL8	-0.2	0.38	-10000	0	-0.77	128	128
POU2F1	0.034	0.017	-10000	0	-10000	0	0

×

EGFR-dependent Endothelin signaling events

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
HRAS	0.032	0.036	-10000	0	-0.42	3	3
EGFR	-0.013	0.13	-10000	0	-0.42	47	47
EGF/EGFR	-0.074	0.18	-10000	0	-0.27	200	200
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.002	0.13	-10000	0	-0.23	104	104
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	-0.004	0.13	-10000	0	-0.42	43	43
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	-0.069	0.19	-10000	0	-0.42	110	110
EGF/EGFR dimer/SHC	-0.03	0.14	-10000	0	-0.26	120	120
mol:GDP	-0.006	0.12	-10000	0	-0.23	104	104
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	-0.038	0.16	-10000	0	-0.42	77	77
GRB2/SOS1	0.047	0.023	-10000	0	-0.3	1	1
HRAS/GTP	-0.018	0.11	-10000	0	-0.22	106	106
SHC1	0.027	0.025	-10000	0	-0.42	1	1
HRAS/GDP	-0.007	0.12	-10000	0	-0.22	106	106
FRAP1	-0.016	0.14	0.37	13	-0.4	4	17
EGF/EGFR dimer	-0.061	0.16	-10000	0	-0.31	151	151
SOS1	0.034	0.021	-10000	0	-0.42	1	1
GRB2	0.033	0.01	-10000	0	-10000	0	0
ETA receptor/Endothelin-1	-0.03	0.16	-10000	0	-0.33	104	104

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.054	0.15	0.35	1	-0.82	9	10
SMARCC2	0.036	0.004	-10000	0	-10000	0	0
SMARCC1	0.032	0.03	-10000	0	-0.42	2	2
TBX21	-0.15	0.28	0.36	1	-0.65	107	108
SUMO2	0.028	0.02	-10000	0	-10000	0	0
STAT1 (dimer)	0.019	0.093	-10000	0	-0.38	24	24
FKBP4	0.029	0.046	-10000	0	-0.42	5	5
FKBP5	-0.004	0.13	-10000	0	-0.42	42	42
GR alpha/HSP90/FKBP51/HSP90	0.06	0.14	0.25	112	-0.25	27	139
PRL	-0.035	0.13	-10000	0	-0.97	2	2
cortisol/GR alpha (dimer)/TIF2	0.13	0.24	0.52	112	-10000	0	112
RELA	-0.022	0.11	-10000	0	-0.22	68	68
FGG	0.14	0.23	0.45	135	-0.38	1	136
GR beta/TIF2	0.069	0.14	0.28	98	-0.29	9	107
IFNG	-0.27	0.41	-10000	0	-0.86	126	126
apoptosis	-0.004	0.17	0.5	5	-0.5	10	15
CREB1	0.038	0.042	-10000	0	-0.37	5	5
histone acetylation	-0.025	0.11	0.31	4	-0.32	36	40
BGLAP	-0.048	0.14	-10000	0	-0.53	11	11
GR/PKAc	0.11	0.12	0.32	54	-0.27	13	67
NF kappa B1 p50/RelA	-0.043	0.19	-10000	0	-0.33	129	129
SMARCD1	0.036	0.004	-10000	0	-10000	0	0
MDM2	0.072	0.1	0.22	133	-10000	0	133
GATA3	-0.039	0.18	-10000	0	-0.42	90	90
AKT1	0.029	0.042	0.19	9	-0.43	3	12
CSF2	-0.05	0.13	-10000	0	-0.86	5	5
GSK3B	0.029	0.02	-10000	0	-10000	0	0
NR1I3	0.03	0.18	0.52	6	-0.61	8	14
CSN2	0.12	0.19	0.38	128	-0.39	3	131
BRG1/BAF155/BAF170/BAF60A	0.083	0.036	-10000	0	-0.24	3	3
NFATC1	0.022	0.09	-10000	0	-0.4	21	21
POU2F1	0.033	0.021	-10000	0	-0.25	1	1
CDKN1A	-0.046	0.26	-10000	0	-1.5	13	13
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.001	0.006	-10000	0	-10000	0	0
SFN	0.011	0.099	-10000	0	-0.42	25	25
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.068	0.14	0.29	59	-0.23	44	103
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.078	0.31	0.46	4	-0.77	78	82
JUN	-0.16	0.23	0.36	4	-0.46	144	148
IL4	-0.087	0.19	-10000	0	-0.48	57	57
CDK5R1	0.032	0.01	-10000	0	-10000	0	0
PRKACA	0.036	0.004	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.097	0.21	0.21	72	-0.37	146	218
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.085	0.13	0.29	68	-0.23	32	100
cortisol/GR alpha (monomer)	0.19	0.31	0.6	150	-0.38	2	152
NCOA2	0.025	0.047	-10000	0	-0.42	5	5
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.083	0.16	-10000	0	-0.44	70	70
AP-1/NFAT1-c-4	-0.27	0.37	-10000	0	-0.71	178	178
AFP	-0.12	0.2	-10000	0	-0.7	14	14
SUV420H1	0.033	0.022	-10000	0	-0.42	1	1
IRF1	0.093	0.21	0.41	62	-0.69	14	76
TP53	0.015	0.12	-10000	0	-0.46	31	31
PPP5C	0.031	0.041	-10000	0	-0.42	4	4
KRT17	-0.39	0.56	-10000	0	-1.2	149	149
KRT14	-0.26	0.49	-10000	0	-1.2	97	97
TBP	0.04	0.018	-10000	0	-0.28	1	1
CREBBP	0.065	0.096	0.28	78	-10000	0	78
HDAC1	0.03	0.021	-10000	0	-0.43	1	1
HDAC2	0.03	0.023	-10000	0	-0.42	1	1
AP-1	-0.28	0.37	-10000	0	-0.71	179	179
MAPK14	0.031	0.016	-10000	0	-10000	0	0
MAPK10	0.008	0.091	-10000	0	-0.42	21	21
MAPK11	0.027	0.02	-10000	0	-10000	0	0
KRT5	-0.39	0.57	-10000	0	-1.2	150	150
interleukin-1 receptor activity	-0.001	0.006	-10000	0	-10000	0	0
NCOA1	0.031	0.048	-10000	0	-0.42	5	5
STAT1	0.019	0.093	-10000	0	-0.38	24	24
CGA	-0.072	0.17	-10000	0	-0.57	26	26
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.082	0.16	0.37	87	-0.36	3	90
MAPK3	0.026	0.028	-10000	0	-0.42	1	1
MAPK1	0.029	0.026	-10000	0	-0.42	1	1
ICAM1	-0.16	0.31	-10000	0	-0.68	101	101
NFKB1	-0.024	0.11	-10000	0	-0.21	89	89
MAPK8	-0.11	0.19	0.48	2	-0.38	127	129
MAPK9	0.014	0.087	-10000	0	-0.42	19	19
cortisol/GR alpha (dimer)	-0.006	0.18	0.5	5	-0.52	10	15
BAX	-0.011	0.1	-10000	0	-10000	0	0
POMC	-0.092	0.2	0.5	1	-1.2	5	6
EP300	0.066	0.097	0.28	84	-0.43	1	85
cortisol/GR alpha (dimer)/p53	0.12	0.25	0.52	109	-0.37	1	110
proteasomal ubiquitin-dependent protein catabolic process	0.053	0.11	0.25	80	-10000	0	80
SGK1	0.081	0.14	0.33	94	-0.42	2	96
IL13	-0.22	0.26	-10000	0	-0.66	83	83
IL6	-0.2	0.38	-10000	0	-0.89	96	96
PRKACG	0.034	0.029	-10000	0	-0.42	2	2
IL5	-0.18	0.22	-10000	0	-0.62	48	48
IL2	-0.22	0.33	-10000	0	-0.72	121	121
CDK5	0.034	0.007	-10000	0	-10000	0	0
PRKACB	0.009	0.097	-10000	0	-0.42	24	24
HSP90AA1	0	0	-10000	0	-10000	0	0
IL8	-0.18	0.34	-10000	0	-0.79	98	98
CDK5R1/CDK5	0.046	0.017	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.004	0.18	-10000	0	-0.34	66	66
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.16	0.24	0.49	144	-10000	0	144
SMARCA4	0.034	0.021	-10000	0	-0.42	1	1
chromatin remodeling	0.11	0.16	0.33	134	-10000	0	134
NF kappa B1 p50/RelA/Cbp	0.022	0.18	0.35	39	-0.36	40	79
JUN (dimer)	-0.16	0.23	0.36	4	-0.46	143	147
YWHAH	0.031	0.036	-10000	0	-0.42	3	3
VIPR1	-0.1	0.21	-10000	0	-0.58	58	58
NR3C1	0.12	0.21	0.39	142	-0.39	8	150
NR4A1	0.037	0.045	-10000	0	-0.44	4	4
TIF2/SUV420H1	0.036	0.046	-10000	0	-0.35	5	5
MAPKKK cascade	-0.004	0.17	0.5	5	-0.5	10	15
cortisol/GR alpha (dimer)/Src-1	0.18	0.26	0.52	150	-0.36	1	151
PBX1	0.019	0.077	-10000	0	-0.41	15	15
POU1F1	0.039	0.025	-10000	0	-0.33	2	2
SELE	-0.24	0.42	-10000	0	-0.92	126	126
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.11	0.16	0.33	134	-10000	0	134
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.16	0.24	0.49	144	-10000	0	144
mol:cortisol	0.11	0.18	0.35	151	-10000	0	151
MMP1	-0.37	0.54	-10000	0	-1.1	165	165

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.035	0.021	-10000	0	-0.42	1	1
CCL5	-0.013	0.14	-10000	0	-0.42	51	51
SDCBP	0.022	0.061	-10000	0	-0.42	9	9
FGFR/FGF2/Syndecan-1	-0.11	0.23	0.22	6	-0.54	88	94
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	-0.11	0.22	-10000	0	-0.52	88	88
Syndecan-1/Syntenin	-0.11	0.22	0.26	1	-0.5	91	92
MAPK3	-0.097	0.2	0.24	1	-0.47	89	90
HGF/MET	0.041	0.057	-10000	0	-0.3	13	13
TGFB1/TGF beta receptor Type II	0.035	0.021	-10000	0	-0.42	1	1
BSG	0.034	0.008	-10000	0	-10000	0	0
keratinocyte migration	-0.11	0.22	-10000	0	-0.51	88	88
Syndecan-1/RANTES	-0.13	0.24	0.26	1	-0.5	112	113
Syndecan-1/CD147	-0.096	0.23	0.27	1	-0.5	91	92
Syndecan-1/Syntenin/PIP2	-0.1	0.21	0.25	1	-0.48	91	92
LAMA5	0.026	0.051	-10000	0	-0.42	6	6
positive regulation of cell-cell adhesion	-0.1	0.21	0.24	1	-0.47	91	92
MMP7	-0.033	0.16	-10000	0	-0.42	69	69
HGF	0.028	0.057	-10000	0	-0.42	8	8
Syndecan-1/CASK	-0.12	0.22	-10000	0	-0.51	92	92
Syndecan-1/HGF/MET	-0.1	0.23	0.27	1	-0.49	94	95
regulation of cell adhesion	-0.1	0.19	0.23	1	-0.46	87	88
HPSE	0.014	0.093	-10000	0	-0.42	22	22
positive regulation of cell migration	-0.11	0.23	0.22	6	-0.54	88	94
SDC1	-0.11	0.23	0.28	1	-0.55	88	89
Syndecan-1/Collagen	-0.11	0.23	0.22	6	-0.54	88	94
PPIB	0.033	0.03	-10000	0	-0.42	2	2
MET	0.029	0.046	-10000	0	-0.42	5	5
PRKACA	0.036	0.004	-10000	0	-10000	0	0
MMP9	-0.014	0.14	-10000	0	-0.42	52	52
MAPK1	-0.1	0.21	0.24	1	-0.47	91	92
homophilic cell adhesion	-0.12	0.22	0.22	6	-0.53	88	94
MMP1	-0.076	0.18	-10000	0	-0.42	109	109

×

HIF-1-alpha transcription factor 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.058	0.35	-9999	-0.74	70	70
HDAC7	0	0.003	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.011	0.34	-9999	-0.72	52	52
SMAD4	0.029	0.054	-9999	-0.42	7	7
ID2	-0.058	0.35	-9999	-0.73	73	73
AP1	-0.035	0.16	-9999	-0.35	89	89
ABCG2	-0.061	0.35	-9999	-0.76	70	70
HIF1A	-0.023	0.16	-9999	-0.47	47	47
TFF3	-0.11	0.37	-9999	-0.75	85	85
GATA2	0.018	0.054	-9999	-0.42	5	5
AKT1	0.009	0.093	-9999	-0.25	14	14
response to hypoxia	-0.008	0.065	-9999	-0.15	32	32
MCL1	-0.06	0.35	-9999	-0.73	73	73
NDRG1	-0.069	0.33	-9999	-0.76	63	63
SERPINE1	-0.065	0.36	-9999	-0.75	73	73
FECH	-0.065	0.36	-9999	-0.75	73	73
FURIN	-0.061	0.35	-9999	-0.73	74	74
NCOA2	0.026	0.047	-9999	-0.42	5	5
EP300	0.007	0.11	-9999	-0.3	27	27
HMOX1	-0.07	0.36	-9999	-0.76	74	74
BHLHE40	-0.08	0.34	-9999	-0.72	74	74
BHLHE41	-0.08	0.34	-9999	-0.72	74	74
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.049	0.17	-9999	-0.33	44	44
ENG	-0.009	0.13	-9999	-0.31	42	42
JUN	-0.009	0.12	-9999	-0.43	39	39
RORA	-0.068	0.36	-9999	-0.74	74	74
ABCB1	-0.03	0.25	-9999	-0.95	28	28
TFRC	-0.075	0.36	-9999	-0.76	76	76
CXCR4	-0.071	0.37	-9999	-0.75	80	80
TF	-0.059	0.35	-9999	-0.75	68	68
CITED2	-0.061	0.35	-9999	-0.75	69	69
HIF1A/ARNT	-0.039	0.42	-9999	-0.88	60	60
LDHA	0.009	0.19	-9999	-0.86	17	17
ETS1	-0.069	0.34	-9999	-0.75	68	68
PGK1	-0.056	0.35	-9999	-0.74	71	71
NOS2	-0.08	0.34	-9999	-0.72	74	74
ITGB2	-0.067	0.36	-9999	-0.75	76	76
ALDOA	-0.054	0.35	-9999	-0.76	64	64
Cbp/p300/CITED2	-0.058	0.36	-9999	-0.82	59	59
FOS	-0.039	0.15	-9999	-0.43	66	66
HK2	-0.058	0.35	-9999	-0.75	68	68
SP1	0.035	0.039	-9999	-0.17	11	11
GCK	0.013	0.18	-9999	-1.2	4	4
HK1	-0.056	0.35	-9999	-0.75	68	68
NPM1	-0.056	0.35	-9999	-0.74	70	70
EGLN1	-0.068	0.33	-9999	-0.75	63	63
CREB1	0.039	0.027	-9999	-0.22	3	3
PGM1	-0.062	0.35	-9999	-0.73	74	74
SMAD3	0.027	0.061	-9999	-0.42	9	9
EDN1	-0.18	0.47	-9999	-1.2	87	87
IGFBP1	-0.057	0.35	-9999	-0.74	70	70
VEGFA	-0.044	0.27	-9999	-0.6	58	58
HIF1A/JAB1	0.002	0.12	-9999	-0.34	42	42
CP	-0.12	0.38	-9999	-0.79	86	86
CXCL12	-0.074	0.37	-9999	-0.77	79	79
COPS5	0.027	0.043	-9999	-0.42	4	4
SMAD3/SMAD4	0.04	0.063	-9999	-0.3	16	16
BNIP3	-0.064	0.36	-9999	-0.75	71	71
EGLN3	-0.083	0.37	-9999	-0.77	82	82
CA9	-0.063	0.35	-9999	-0.74	70	70
TERT	-0.058	0.35	-9999	-0.76	67	67
ENO1	-0.059	0.35	-9999	-0.76	67	67
PFKL	-0.059	0.35	-9999	-0.75	70	70
NCOA1	0.031	0.046	-9999	-0.42	5	5
ADM	-0.082	0.38	-9999	-0.77	83	83
ARNT	0.014	0.077	-9999	-10000	0	0
HNF4A	0.034	0.033	-9999	-0.25	5	5
ADFP	-0.067	0.36	-9999	-0.77	73	73
SLC2A1	-0.032	0.28	-9999	-0.61	56	56
LEP	-0.077	0.36	-9999	-0.75	73	73
HIF1A/ARNT/Cbp/p300	-0.025	0.34	-9999	-0.73	55	55
EPO	-0.029	0.27	-9999	-0.72	37	37
CREBBP	0.015	0.097	-9999	-0.29	16	16
HIF1A/ARNT/Cbp/p300/HDAC7	-0.024	0.33	-9999	-0.71	53	53
PFKFB3	-0.061	0.35	-9999	-0.76	68	68
NT5E	-0.06	0.36	-9999	-0.75	72	72

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.029	0.05	-10000	0	-0.42	6	6
LAT2	-0.049	0.14	-10000	0	-0.31	85	85
AP1	-0.059	0.21	0.29	1	-0.47	71	72
mol:PIP3	-0.023	0.19	0.31	23	-0.37	78	101
IKBKB	0.013	0.14	0.25	54	-0.24	43	97
AKT1	0.014	0.18	0.33	79	-0.37	24	103
IKBKG	-0.007	0.12	0.19	58	-0.24	46	104
MS4A2	-0.076	0.19	-10000	0	-0.41	120	120
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
MAP3K1	-0.039	0.17	0.25	12	-0.39	60	72
mol:Ca2+	-0.011	0.16	0.26	30	-0.32	52	82
LYN	0.031	0.018	-10000	0	-10000	0	0
CBLB	-0.048	0.13	-10000	0	-0.31	84	84
SHC1	0.027	0.025	-10000	0	-0.42	1	1
RasGAP/p62DOK	0.034	0.095	-10000	0	-0.25	47	47
positive regulation of cell migration	-0.007	0.066	-10000	0	-0.3	25	25
INPP5D	0	0	-10000	0	-10000	0	0
PLD2	-0.003	0.18	0.31	78	-0.26	91	169
PTPN13	-0.068	0.2	-10000	0	-0.54	45	45
PTPN11	0.033	0.024	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.003	0.15	0.32	23	-0.32	31	54
SYK	0.007	0.12	-10000	0	-0.43	33	33
GRB2	0.033	0.011	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.056	0.16	-10000	0	-0.37	85	85
LAT	-0.046	0.13	-10000	0	-0.3	83	83
PAK2	-0.033	0.17	0.26	12	-0.42	51	63
NFATC2	-0.012	0.066	-10000	0	-0.59	4	4
HRAS	-0.034	0.18	0.27	14	-0.44	51	65
GAB2	0.031	0.013	-10000	0	-10000	0	0
PLA2G1B	0.008	0.12	-10000	0	-0.92	7	7
Fc epsilon R1	-0.03	0.16	-10000	0	-0.31	109	109
Antigen/IgE/Fc epsilon R1	-0.025	0.14	-10000	0	-0.27	109	109
mol:GDP	-0.051	0.18	0.25	1	-0.48	51	52
JUN	-0.001	0.12	-10000	0	-0.42	39	39
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
FOS	-0.031	0.15	-10000	0	-0.42	66	66
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.044	0.14	-10000	0	-0.32	85	85
CHUK	-0.01	0.12	0.19	53	-0.25	50	103
KLRG1	-0.039	0.12	-10000	0	-0.37	39	39
VAV1	-0.051	0.14	-10000	0	-0.32	86	86
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.047	0.13	-10000	0	-0.31	82	82
negative regulation of mast cell degranulation	-0.041	0.11	-10000	0	-0.35	38	38
BTK	-0.057	0.18	-10000	0	-0.52	47	47
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.063	0.18	-10000	0	-0.34	117	117
GAB2/PI3K/SHP2	-0.053	0.1	-10000	0	-0.3	51	51
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.048	0.13	-10000	0	-0.26	108	108
RAF1	0.009	0.13	-10000	0	-1	7	7
Fc epsilon R1/FcgammaRIIB/SHIP	-0.025	0.16	-10000	0	-0.29	116	116
FCER1G	0.032	0.019	-10000	0	-10000	0	0
FCER1A	-0.023	0.14	-10000	0	-0.43	55	55
Antigen/IgE/Fc epsilon R1/Fyn	-0.015	0.14	-10000	0	-0.26	106	106
MAPK3	0.008	0.12	-10000	0	-0.95	7	7
MAPK1	0.003	0.12	-10000	0	-0.92	7	7
NFKB1	0.035	0.005	-10000	0	-10000	0	0
MAPK8	-0.039	0.22	-10000	0	-0.65	43	43
DUSP1	0.001	0.12	-10000	0	-0.42	35	35
NF-kappa-B/RelA	0.011	0.084	0.16	31	-0.16	31	62
actin cytoskeleton reorganization	-0.042	0.18	-10000	0	-0.52	34	34
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.027	0.18	-10000	0	-0.43	49	49
FER	-0.046	0.13	-10000	0	-0.31	84	84
RELA	0.035	0.006	-10000	0	-10000	0	0
ITK	-0.032	0.11	-10000	0	-0.39	39	39
SOS1	0.035	0.021	-10000	0	-0.42	1	1
PLCG1	-0.039	0.19	0.26	6	-0.47	51	57
cytokine secretion	-0.003	0.051	-10000	0	-0.13	12	12
SPHK1	-0.054	0.14	-10000	0	-0.32	84	84
PTK2	-0.045	0.19	-10000	0	-0.55	33	33
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.057	0.17	-10000	0	-0.38	86	86
EDG1	-0.007	0.066	-10000	0	-0.3	25	25
mol:DAG	-0.028	0.19	0.31	18	-0.43	54	72
MAP2K2	0.003	0.12	-10000	0	-0.94	7	7
MAP2K1	0.005	0.12	-10000	0	-0.94	7	7
MAP2K7	0.034	0.021	-10000	0	-0.42	1	1
KLRG1/SHP2	-0.025	0.12	0.25	1	-0.36	33	34
MAP2K4	-0.097	0.35	-10000	0	-0.93	75	75
Fc epsilon R1/FcgammaRIIB	-0.026	0.17	-10000	0	-0.31	116	116
mol:Choline	-0.002	0.18	0.31	78	-0.26	91	169
SHC/Grb2/SOS1	-0.011	0.14	-10000	0	-0.38	34	34
FYN	0.027	0.05	-10000	0	-0.42	6	6
DOK1	0.027	0.061	-10000	0	-0.42	9	9
PXN	-0.043	0.18	-10000	0	-0.5	34	34
HCLS1	-0.051	0.14	-10000	0	-0.32	87	87
PRKCB	-0.015	0.15	0.25	30	-0.32	50	80
FCGR2B	0.002	0.11	-10000	0	-0.42	29	29
IGHE	0.001	0.009	-10000	0	-10000	0	0
KLRG1/SHIP	-0.042	0.12	-10000	0	-0.35	38	38
LCP2	0.023	0.07	-10000	0	-0.42	12	12
PLA2G4A	-0.052	0.14	-10000	0	-0.32	88	88
RASA1	0.028	0.054	-10000	0	-0.42	7	7
mol:Phosphatidic acid	-0.002	0.18	0.31	78	-0.26	91	169
IKK complex	0.012	0.12	0.24	49	-0.2	31	80
WIPF1	0	0	-10000	0	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.003	0.17	0.24	40	-0.34	70	110
FYN	-0.039	0.2	0.28	5	-0.42	80	85
LAT/GRAP2/SLP76	-0.021	0.17	0.24	10	-0.35	82	92
IKBKB	0.029	0.014	-10000	0	-10000	0	0
AKT1	-0.027	0.15	0.25	15	-0.31	83	98
B2M	0.025	0.065	-10000	0	-0.43	10	10
IKBKG	0	0.056	0.13	20	-0.13	27	47
MAP3K8	0.003	0.11	-10000	0	-0.42	32	32
mol:Ca2+	-0.017	0.02	0.089	1	-0.058	70	71
integrin-mediated signaling pathway	0.029	0.048	-10000	0	-0.25	12	12
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.053	0.2	0.26	2	-0.43	89	91
TRPV6	-0.03	0.22	1.2	9	-0.42	59	68
CD28	-0.002	0.12	-10000	0	-0.43	38	38
SHC1	-0.022	0.2	0.24	47	-0.39	84	131
receptor internalization	-0.07	0.2	-10000	0	-0.4	125	125
PRF1	-0.052	0.22	-10000	0	-0.88	22	22
KRAS	0.027	0.057	-10000	0	-0.42	8	8
GRB2	0.033	0.01	-10000	0	-10000	0	0
COT/AKT1	-0.016	0.14	0.24	14	-0.28	77	91
LAT	-0.043	0.19	0.24	14	-0.38	95	109
EntrezGene:6955	0	0.003	-10000	0	-0.016	8	8
CD3D	0.016	0.074	-10000	0	-0.43	13	13
CD3E	0.031	0.015	-10000	0	-10000	0	0
CD3G	-0.022	0.14	-10000	0	-0.43	54	54
RASGRP2	-0.001	0.044	-10000	0	-0.17	28	28
RASGRP1	-0.043	0.17	0.28	4	-0.34	93	97
HLA-A	0.017	0.089	-10000	0	-0.43	19	19
RASSF5	0.019	0.061	-10000	0	-0.42	9	9
RAP1A/GTP/RAPL	0.03	0.049	-10000	0	-0.25	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.016	0.067	0.14	37	-0.12	29	66
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.022	0.071	-10000	0	-0.18	58	58
PRKCA	-0.01	0.092	0.18	17	-0.22	47	64
GRAP2	0.032	0.023	-10000	0	-0.42	1	1
mol:IP3	-0.021	0.14	0.21	33	-0.31	64	97
EntrezGene:6957	0	0.004	0.011	2	-0.021	8	10
TCR/CD3/MHC I/CD8	-0.032	0.15	-10000	0	-0.36	65	65
ORAI1	0.007	0.16	0.48	2	-1	9	11
CSK	-0.047	0.18	0.26	2	-0.39	87	89
B7 family/CD28	-0.03	0.22	0.29	1	-0.47	77	78
CHUK	0.025	0.067	-10000	0	-0.42	11	11
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.061	0.21	0.26	1	-0.42	104	105
PTPN6	-0.055	0.19	0.24	4	-0.39	94	98
VAV1	-0.06	0.2	0.26	2	-0.41	102	104
Monovalent TCR/CD3	-0.018	0.11	-10000	0	-0.3	61	61
CBL	0.031	0.012	-10000	0	-10000	0	0
LCK	-0.048	0.21	0.25	5	-0.44	86	91
PAG1	-0.032	0.19	0.23	12	-0.39	87	99
RAP1A	0.03	0.05	-10000	0	-0.42	6	6
TCR/CD3/MHC I/CD8/LCK	-0.063	0.21	0.28	1	-0.42	105	106
CD80	0.033	0.022	-10000	0	-0.42	1	1
CD86	0.016	0.092	-10000	0	-0.43	21	21
PDK1/CARD11/BCL10/MALT1	-0.015	0.091	-10000	0	-0.21	61	61
HRAS	0.032	0.036	-10000	0	-0.42	3	3
GO:0035030	-0.054	0.17	0.25	1	-0.4	79	80
CD8A	0	0.003	0.011	2	-0.018	8	10
CD8B	0	0.004	0.011	3	-0.015	17	20
PTPRC	0.005	0.098	-10000	0	-0.43	24	24
PDK1/PKC theta	-0.029	0.18	0.31	22	-0.37	81	103
CSK/PAG1	-0.027	0.18	0.23	11	-0.4	73	84
SOS1	0.034	0.021	-10000	0	-0.42	1	1
peptide-MHC class I	0.031	0.091	-10000	0	-0.35	25	25
GRAP2/SLP76	-0.035	0.2	0.29	1	-0.38	98	99
STIM1	0.006	0.092	1.3	2	-10000	0	2
RAS family/GTP	0.012	0.086	0.18	7	-0.18	36	43
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.074	0.21	-10000	0	-0.41	125	125
mol:DAG	-0.042	0.11	0.12	1	-0.26	84	85
RAP1A/GDP	0.011	0.035	0.076	18	-0.07	17	35
PLCG1	0.033	0.009	-10000	0	-10000	0	0
CD247	0	0.003	-10000	0	-0.016	8	8
cytotoxic T cell degranulation	-0.049	0.21	-10000	0	-0.83	22	22
RAP1A/GTP	0	0.018	-10000	0	-0.065	33	33
mol:PI-3-4-5-P3	-0.042	0.17	0.23	3	-0.36	89	92
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.021	0.17	0.24	24	-0.39	64	88
NRAS	0.029	0.05	-10000	0	-0.42	6	6
ZAP70	0.033	0.022	-10000	0	-0.42	1	1
GRB2/SOS1	0.047	0.023	-10000	0	-0.3	1	1
LAT/GRAP2/SLP76/VAV1	-0.031	0.17	0.22	9	-0.37	76	85
MALT1	0.031	0.041	-10000	0	-0.42	4	4
TRAF6	0.034	0.021	-10000	0	-0.42	1	1
CD8 heterodimer	0.001	0.006	0.02	3	-0.022	12	15
CARD11	0.027	0.054	-10000	0	-0.42	7	7
PRKCB	-0.034	0.077	0.11	4	-0.18	85	89
PRKCE	-0.011	0.098	0.18	19	-0.22	52	71
PRKCQ	-0.046	0.19	0.27	5	-0.4	89	94
LCP2	0.023	0.07	-10000	0	-0.42	12	12
BCL10	0.034	0.008	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.02	0.13	0.23	17	-0.27	83	100
IKK complex	0.014	0.063	0.16	36	-0.11	14	50
RAS family/GDP	-0.004	0.015	-10000	0	-0.049	19	19
MAP3K14	-0.015	0.11	0.19	17	-0.22	70	87
PDPK1	-0.022	0.15	0.28	20	-0.3	80	100
TCR/CD3/MHC I/CD8/Fyn	-0.062	0.21	-10000	0	-0.43	93	93

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.039	0.19	-10000	0	-0.59	52	52
IHH	0.017	0.088	-10000	0	-0.28	24	24
SHH Np/Cholesterol/GAS1	-0.026	0.1	-10000	0	-0.24	98	98
LRPAP1	0.035	0.007	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.026	0.1	0.24	98	-10000	0	98
SMO/beta Arrestin2	-0.02	0.17	-10000	0	-0.41	55	55
SMO	-0.036	0.16	-10000	0	-0.42	54	54
AKT1	-0.013	0.16	-10000	0	-0.55	28	28
ARRB2	0.032	0.011	-10000	0	-10000	0	0
BOC	0.015	0.089	-10000	0	-0.42	20	20
ADRBK1	0.033	0.01	-10000	0	-10000	0	0
heart looping	-0.035	0.16	-10000	0	-0.42	54	54
STIL	-0.005	0.13	0.2	70	-0.26	51	121
DHH N/PTCH2	0.051	0.011	-10000	0	-10000	0	0
DHH N/PTCH1	0	0.12	-10000	0	-0.29	68	68
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
DHH	0.036	0.004	-10000	0	-10000	0	0
PTHLH	-0.064	0.25	-10000	0	-0.74	55	55
determination of left/right symmetry	-0.035	0.16	-10000	0	-0.42	54	54
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
skeletal system development	-0.063	0.25	-10000	0	-0.73	55	55
IHH N/Hhip	0.034	0.065	-10000	0	-0.29	12	12
DHH N/Hhip	0.049	0.029	-10000	0	-0.3	3	3
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.035	0.16	-10000	0	-0.42	54	54
pancreas development	0.032	0.036	-10000	0	-0.42	3	3
HHAT	-0.016	0.13	-10000	0	-0.42	49	49
PI3K	0.035	0.067	-10000	0	-0.3	18	18
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.03	0.16	-10000	0	-0.42	71	71
somite specification	-0.035	0.16	-10000	0	-0.42	54	54
SHH Np/Cholesterol/PTCH1	-0.03	0.11	-10000	0	-0.24	100	100
SHH Np/Cholesterol/PTCH2	0.003	0.074	-10000	0	-0.23	43	43
SHH Np/Cholesterol/Megalin	-0.056	0.14	-10000	0	-0.27	134	134
SHH	-0.016	0.09	-10000	0	-0.3	45	45
catabolic process	-0.024	0.12	-10000	0	-0.32	69	69
SMO/Vitamin D3	-0.018	0.15	-10000	0	-0.33	60	60
SHH Np/Cholesterol/Hhip	0.002	0.074	-10000	0	-0.23	44	44
LRP2	-0.098	0.21	-10000	0	-0.42	146	146
receptor-mediated endocytosis	-0.071	0.17	-10000	0	-0.37	89	89
SHH Np/Cholesterol/BOC	-0.007	0.085	-10000	0	-0.23	61	61
SHH Np/Cholesterol/CDO	-0.007	0.083	-10000	0	-0.24	56	56
mesenchymal cell differentiation	-0.002	0.074	0.23	44	-10000	0	44
mol:Vitamin D3	-0.005	0.13	0.2	61	-0.24	96	157
IHH N/PTCH2	0.036	0.06	-10000	0	-0.27	10	10
CDON	0.019	0.07	-10000	0	-0.42	12	12
IHH N/PTCH1	-0.004	0.13	-10000	0	-0.32	69	69
Megalin/LRPAP1	-0.051	0.16	-10000	0	-0.3	146	146
PTCH2	0.035	0.006	-10000	0	-10000	0	0
SHH Np/Cholesterol	-0.007	0.07	-10000	0	-0.23	45	45
PTCH1	-0.024	0.12	-10000	0	-0.32	69	69
HHIP	0.032	0.036	-10000	0	-0.42	3	3

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.016	0.085	-10000	0	-0.42	18	18
GNB1/GNG2	-0.051	0.08	-10000	0	-0.18	129	129
AKT1	-0.015	0.12	0.23	5	-0.23	48	53
EGF	-0.069	0.19	-10000	0	-0.42	110	110
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.014	0.065	0.25	5	-0.26	3	8
mol:Ca2+	-0.037	0.17	-10000	0	-0.3	128	128
LYN	0.013	0.058	0.26	4	-0.28	2	6
RhoA/GTP	-0.016	0.075	-10000	0	-0.13	111	111
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.057	0.19	-10000	0	-0.35	131	131
GNG2	0.034	0.021	-10000	0	-0.42	1	1
ARRB2	0.032	0.011	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.013	0.14	-10000	0	-0.47	31	31
G beta5/gamma2	-0.054	0.11	-10000	0	-0.24	124	124
PRKCH	-0.053	0.2	0.3	3	-0.36	132	135
DNM1	0.032	0.041	-10000	0	-0.42	4	4
TXA2/TP beta/beta Arrestin3	0.028	0.027	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	0.027	0.054	-10000	0	-0.42	7	7
G12 family/GTP	-0.051	0.16	-10000	0	-0.3	119	119
ADRBK1	0.033	0.01	-10000	0	-10000	0	0
ADRBK2	0.022	0.07	-10000	0	-0.42	12	12
RhoA/GTP/ROCK1	0.04	0.04	-10000	0	-0.25	8	8
mol:GDP	0.024	0.14	0.43	32	-0.23	2	34
mol:NADP	0.035	0.007	-10000	0	-10000	0	0
RAB11A	0.034	0.021	-10000	0	-0.42	1	1
PRKG1	0.035	0.005	-10000	0	-10000	0	0
mol:IP3	-0.055	0.21	-10000	0	-0.38	130	130
cell morphogenesis	0.04	0.04	-10000	0	-0.25	8	8
PLCB2	-0.089	0.27	-10000	0	-0.52	129	129
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.006	0.06	0.25	4	-0.28	2	6
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.008	0.076	0.25	5	-0.34	7	12
RHOA	0.026	0.061	-10000	0	-0.42	9	9
PTGIR	0.033	0.03	-10000	0	-0.42	2	2
PRKCB1	-0.058	0.21	-10000	0	-0.4	122	122
GNAQ	0	0	-10000	0	-10000	0	0
mol:L-citrulline	0.035	0.007	-10000	0	-10000	0	0
TXA2/TXA2-R family	-0.09	0.27	-10000	0	-0.52	131	131
LCK	-0.006	0.092	0.25	5	-0.32	12	17
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.049	0.047	0.23	1	-0.26	1	2
TXA2-R family/G12 family/GDP/G beta/gamma	0.035	0.094	-10000	0	-0.48	13	13
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.043	0.047	0.23	1	-0.25	1	2
MAPK14	-0.033	0.13	0.22	3	-0.24	127	130
TGM2/GTP	-0.066	0.22	-10000	0	-0.42	125	125
MAPK11	-0.034	0.13	0.25	3	-0.23	129	132
ARHGEF1	-0.013	0.11	0.22	5	-0.18	112	117
GNAI2	0.027	0.057	-10000	0	-0.42	8	8
JNK cascade	-0.056	0.21	-10000	0	-0.38	131	131
RAB11/GDP	0.034	0.021	-10000	0	-0.42	1	1
ICAM1	-0.039	0.16	-10000	0	-0.3	130	130
cAMP biosynthetic process	-0.051	0.19	-10000	0	-0.35	123	123
Gq family/GTP/EBP50	-0.022	0.096	-10000	0	-0.23	80	80
actin cytoskeleton reorganization	0.04	0.04	-10000	0	-0.25	8	8
SRC	0.014	0.065	0.25	5	-0.27	2	7
GNB5	0.024	0.067	-10000	0	-0.42	11	11
GNB1	0.032	0.045	-10000	0	-0.42	5	5
EGF/EGFR	-0.033	0.11	0.25	8	-0.3	35	43
VCAM1	-0.042	0.17	-10000	0	-0.31	131	131
TP beta/Gq family/GDP/G beta5/gamma2	-0.013	0.14	-10000	0	-0.47	31	31
platelet activation	-0.042	0.17	0.31	1	-0.3	129	130
PGI2/IP	0.024	0.021	-10000	0	-0.3	2	2
PRKACA	0.018	0.035	-10000	0	-0.23	9	9
Gq family/GDP/G beta5/gamma2	-0.008	0.12	-10000	0	-0.41	30	30
TXA2/TP beta/beta Arrestin2	0.008	0.069	-10000	0	-0.44	7	7
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.008	0.029	-10000	0	-0.21	8	8
mol:DAG	-0.066	0.23	-10000	0	-0.43	131	131
EGFR	-0.013	0.13	-10000	0	-0.42	47	47
TXA2/TP alpha	-0.077	0.25	-10000	0	-0.48	123	123
Gq family/GTP	-0.017	0.078	0.22	2	-0.22	59	61
YES1	0.013	0.07	0.25	5	-0.29	6	11
GNAI2/GTP	0.02	0.055	-10000	0	-0.27	4	4
PGD2/DP	0.02	0.038	-10000	0	-0.3	7	7
SLC9A3R1	-0.009	0.13	-10000	0	-0.42	46	46
FYN	0.01	0.069	0.25	4	-0.3	6	10
mol:NO	0.035	0.007	-10000	0	-10000	0	0
GNA15	0.029	0.046	-10000	0	-0.42	5	5
PGK/cGMP	0.046	0.011	-10000	0	-10000	0	0
RhoA/GDP	0.026	0.06	-10000	0	-0.42	9	9
TP alpha/TGM2/GDP/G beta/gamma	0.053	0.074	0.28	2	-0.32	4	6
NOS3	0.035	0.007	-10000	0	-10000	0	0
RAC1	0.035	0.006	-10000	0	-10000	0	0
PRKCA	-0.043	0.19	0.3	4	-0.35	116	120
PRKCB	-0.054	0.19	-10000	0	-0.36	132	132
PRKCE	-0.054	0.2	0.29	2	-0.36	129	131
PRKCD	-0.061	0.2	-10000	0	-0.39	130	130
PRKCG	-0.06	0.21	-10000	0	-0.39	133	133
muscle contraction	-0.083	0.25	-10000	0	-0.48	132	132
PRKCZ	-0.048	0.18	-10000	0	-0.34	131	131
ARR3	0.036	0.002	-10000	0	-10000	0	0
TXA2/TP beta	0.04	0.058	0.27	1	-0.22	9	10
PRKCQ	-0.05	0.2	0.3	1	-0.37	124	125
MAPKKK cascade	-0.073	0.24	-10000	0	-0.45	131	131
SELE	-0.058	0.19	-10000	0	-0.37	130	130
TP beta/GNAI2/GDP/G beta/gamma	0.061	0.068	0.28	2	-0.4	3	5
ROCK1	0.035	0.005	-10000	0	-10000	0	0
GNA14	-0.01	0.13	-10000	0	-0.42	44	44
chemotaxis	-0.11	0.31	-10000	0	-0.61	131	131
GNA12	0.035	0.006	-10000	0	-10000	0	0
GNA13	0.028	0.042	-10000	0	-0.42	4	4
GNA11	0.032	0.036	-10000	0	-0.42	3	3
Rac1/GTP	0.026	0.005	-10000	0	-10000	0	0

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.006	0.1	-10000	0	-0.33	20	20
TBX21	-0.26	0.57	-10000	0	-1.3	108	108
B2M	0.023	0.066	-10000	0	-0.42	10	10
TYK2	0.013	0.042	-10000	0	-10000	0	0
IL12RB1	0.013	0.043	-10000	0	-10000	0	0
GADD45B	-0.18	0.44	-10000	0	-1.1	82	82
IL12RB2	-0.011	0.1	-10000	0	-0.43	26	26
GADD45G	-0.17	0.42	-10000	0	-1	84	84
natural killer cell activation	-0.005	0.022	-10000	0	-0.04	118	118
RELB	0.029	0.05	-10000	0	-0.42	6	6
RELA	0.035	0.006	-10000	0	-10000	0	0
IL18	-0.001	0.11	-10000	0	-0.43	32	32
IL2RA	0.004	0.11	-10000	0	-0.42	31	31
IFNG	-0.008	0.12	-10000	0	-0.42	38	38
STAT3 (dimer)	-0.14	0.36	-10000	0	-0.8	99	99
HLA-DRB5	0.014	0.082	-10000	0	-0.42	16	16
FASLG	-0.18	0.49	-10000	0	-1.1	88	88
NF kappa B2 p52/RelB	-0.16	0.44	-10000	0	-0.95	100	100
CD4	0.028	0.021	-10000	0	-10000	0	0
SOCS1	0.031	0.023	-10000	0	-0.42	1	1
EntrezGene:6955	-0.003	0.012	-10000	0	-0.03	67	67
CD3D	0.009	0.076	-10000	0	-0.43	13	13
CD3E	0.024	0.026	-10000	0	-10000	0	0
CD3G	-0.028	0.14	-10000	0	-0.43	54	54
IL12Rbeta2/JAK2	0.003	0.095	-10000	0	-0.33	26	26
CCL3	-0.17	0.43	-10000	0	-1	90	90
CCL4	-0.18	0.45	-10000	0	-1	87	87
HLA-A	0.016	0.088	-10000	0	-0.42	19	19
IL18/IL18R	-0.003	0.17	-10000	0	-0.35	84	84
NOS2	-0.18	0.43	-10000	0	-0.88	113	113
IL12/IL12R/TYK2/JAK2/SPHK2	-0.01	0.11	-10000	0	-0.36	19	19
IL1R1	-0.22	0.5	-10000	0	-1.1	103	103
IL4	0.034	0.052	-10000	0	-0.42	5	5
JAK2	0.011	0.051	-10000	0	-0.46	2	2
EntrezGene:6957	-0.003	0.012	-10000	0	-0.029	66	66
TCR/CD3/MHC I/CD8	-0.071	0.27	-10000	0	-0.77	49	49
RAB7A	-0.13	0.34	-10000	0	-0.77	95	95
lysosomal transport	-0.12	0.32	-10000	0	-0.72	95	95
FOS	-0.24	0.5	-10000	0	-1.1	105	105
STAT4 (dimer)	-0.15	0.41	-10000	0	-0.9	98	98
STAT5A (dimer)	-0.18	0.44	-10000	0	-0.96	100	100
GZMA	-0.18	0.42	-10000	0	-0.92	101	101
GZMB	-0.26	0.56	-10000	0	-1.3	104	104
HLX	0	0	-10000	0	-10000	0	0
LCK	-0.21	0.5	-10000	0	-1.1	105	105
TCR/CD3/MHC II/CD4	-0.058	0.17	-10000	0	-0.37	91	91
IL2/IL2R	0.042	0.11	-10000	0	-0.29	45	45
MAPK14	-0.18	0.44	-10000	0	-1	95	95
CCR5	-0.17	0.4	-10000	0	-0.82	113	113
IL1B	-0.022	0.13	-10000	0	-0.45	40	40
STAT6	-0.056	0.2	-10000	0	-0.59	35	35
STAT4	0.01	0.1	-10000	0	-0.42	26	26
STAT3	0.028	0.031	-10000	0	-0.42	2	2
STAT1	0.02	0.075	-10000	0	-0.42	14	14
NFKB1	0.035	0.005	-10000	0	-10000	0	0
NFKB2	0.034	0.021	-10000	0	-0.42	1	1
IL12B	0.008	0.066	-10000	0	-0.42	7	7
CD8A	0	0.008	-10000	0	-0.038	18	18
CD8B	0	0.009	-10000	0	-0.045	19	19
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.006	0.1	0.33	20	-10000	0	20
IL2RB	0.012	0.095	-10000	0	-0.42	23	23
proteasomal ubiquitin-dependent protein catabolic process	-0.13	0.37	-10000	0	-0.8	98	98
IL2RG	0.03	0.041	-10000	0	-0.42	4	4
IL12	0.014	0.076	-10000	0	-0.33	10	10
STAT5A	0.028	0.037	-10000	0	-0.42	3	3
CD247	-0.002	0.011	-10000	0	-0.027	65	65
IL2	0.032	0.036	-10000	0	-0.42	3	3
SPHK2	0.034	0.021	-10000	0	-0.42	1	1
FRAP1	0.034	0.008	-10000	0	-10000	0	0
IL12A	0.005	0.059	-10000	0	-0.43	5	5
IL12/IL12R/TYK2/JAK2	-0.22	0.53	-10000	0	-1.1	101	101
MAP2K3	-0.19	0.46	-10000	0	-1	98	98
RIPK2	0.028	0.015	-10000	0	-10000	0	0
MAP2K6	-0.18	0.44	-10000	0	-1	93	93
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.019	0.064	-10000	0	-0.42	9	9
IL18RAP	-0.023	0.15	-10000	0	-0.43	60	60
IL12Rbeta1/TYK2	0.026	0.056	-10000	0	-10000	0	0
EOMES	-0.046	0.27	-10000	0	-1.2	26	26
STAT1 (dimer)	-0.15	0.38	-10000	0	-0.81	103	103
T cell proliferation	-0.11	0.3	-10000	0	-0.64	102	102
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.016	0.091	-10000	0	-0.43	20	20
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.11	0.33	-10000	0	-0.67	108	108
ATF2	-0.16	0.4	-10000	0	-0.9	95	95

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.035	0.021	-10000	0	-0.42	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.1	0.25	0.63	69	-0.52	2	71
IL27/IL27R/JAK1	-0.09	0.34	0.88	2	-1	45	47
TBX21	-0.097	0.3	0.59	25	-0.56	106	131
IL12B	0.025	0.055	-10000	0	-0.42	7	7
IL12A	0.003	0.031	-10000	0	-0.3	5	5
IL6ST	-0.05	0.16	-10000	0	-0.4	87	87
IL27RA/JAK1	-0.062	0.33	0.41	3	-1.2	35	38
IL27	-0.038	0.16	-10000	0	-0.43	74	74
TYK2	0.028	0.029	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.014	0.086	0.2	12	-0.25	54	66
T-helper 2 cell differentiation	0.1	0.25	0.63	69	-0.52	2	71
T cell proliferation during immune response	0.1	0.25	0.63	69	-0.52	2	71
MAPKKK cascade	-0.1	0.25	0.52	2	-0.63	69	71
STAT3	0.028	0.031	-10000	0	-0.42	2	2
STAT2	0.035	0.005	-10000	0	-10000	0	0
STAT1	0.022	0.077	-10000	0	-0.42	14	14
IL12RB1	0.035	0.006	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.081	0.29	0.61	24	-0.59	79	103
IL27/IL27R/JAK2/TYK2	-0.1	0.26	0.52	2	-0.64	68	70
positive regulation of T cell mediated cytotoxicity	-0.1	0.25	0.52	2	-0.63	69	71
STAT1 (dimer)	-0.1	0.39	0.56	32	-0.87	70	102
JAK2	0.024	0.038	-10000	0	-0.43	2	2
JAK1	0.034	0.036	-10000	0	-0.39	3	3
STAT2 (dimer)	-0.088	0.25	0.46	2	-0.6	69	71
T cell proliferation	-0.12	0.26	0.47	2	-0.61	78	80
IL12/IL12R/TYK2/JAK2	-0.004	0.21	-10000	0	-0.93	19	19
IL17A	-0.014	0.087	0.2	12	-0.25	54	66
mast cell activation	0.1	0.25	0.63	69	-0.52	2	71
IFNG	-0.01	0.05	0.13	6	-0.12	55	61
T cell differentiation	-0.005	0.011	0.029	13	-0.023	91	104
STAT3 (dimer)	-0.079	0.24	0.46	2	-0.61	65	67
STAT5A (dimer)	-0.08	0.24	0.46	2	-0.61	65	67
STAT4 (dimer)	-0.098	0.26	0.46	2	-0.6	78	80
STAT4	0.01	0.1	-10000	0	-0.42	26	26
T cell activation	-0.002	0.032	0.12	31	-10000	0	31
IL27R/JAK2/TYK2	-0.08	0.32	-10000	0	-1.1	38	38
GATA3	-0.2	0.52	0.78	8	-1.3	90	98
IL18	-0.013	0.074	-10000	0	-0.3	32	32
positive regulation of mast cell cytokine production	-0.077	0.24	0.46	2	-0.59	65	67
IL27/EBI3	-0.01	0.13	0.23	4	-0.31	77	81
IL27RA	-0.091	0.33	0.38	3	-1.3	35	38
IL6	-0.019	0.14	-10000	0	-0.42	53	53
STAT5A	0.028	0.037	-10000	0	-0.42	3	3
monocyte differentiation	0	0.002	-10000	0	-0.015	1	1
IL2	0.022	0.15	0.47	35	-1.2	3	38
IL1B	-0.017	0.083	-10000	0	-0.3	40	40
EBI3	0.026	0.053	-10000	0	-0.43	5	5
TNF	0.002	0.041	-10000	0	-0.3	9	9

×

IL23-mediated 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.16	0.54	-10000	0	-1.3	79	79
IL23A	-0.14	0.49	-10000	0	-1.2	65	65
NF kappa B1 p50/RelA/I kappa B alpha	-0.1	0.48	-10000	0	-1.1	71	71
positive regulation of T cell mediated cytotoxicity	-0.14	0.52	-10000	0	-1.2	70	70
ITGA3	-0.14	0.48	-10000	0	-1.1	73	73
IL17F	-0.053	0.33	0.47	4	-0.69	72	76
IL12B	0.018	0.078	-10000	0	-0.44	7	7
STAT1 (dimer)	-0.15	0.5	-10000	0	-1.2	71	71
CD4	-0.11	0.45	-10000	0	-1.1	65	65
IL23	-0.13	0.47	-10000	0	-1.2	64	64
IL23R	-0.002	0.22	-10000	0	-1.3	11	11
IL1B	-0.16	0.53	-10000	0	-1.3	74	74
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.082	0.46	-10000	0	-1.1	60	60
TYK2	0.019	0.046	-10000	0	-10000	0	0
STAT4	0.01	0.1	-10000	0	-0.42	26	26
STAT3	0.029	0.031	-10000	0	-0.42	2	2
IL18RAP	-0.024	0.15	-10000	0	-0.43	60	60
IL12RB1	0.019	0.046	-10000	0	-10000	0	0
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
IL12Rbeta1/TYK2	0.029	0.059	-10000	0	-10000	0	0
IL23R/JAK2	0.01	0.22	-10000	0	-1.2	11	11
positive regulation of chronic inflammatory response	-0.14	0.52	-10000	0	-1.2	70	70
natural killer cell activation	0.001	0.012	0.081	7	-10000	0	7
JAK2	0.022	0.063	-10000	0	-0.46	2	2
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
NFKB1	0.036	0.007	-10000	0	-10000	0	0
RELA	0.036	0.007	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.12	0.45	-10000	0	-1.1	66	66
ALOX12B	-0.12	0.45	-10000	0	-1.1	66	66
CXCL1	-0.18	0.55	-10000	0	-1.2	103	103
T cell proliferation	-0.14	0.52	-10000	0	-1.2	70	70
NFKBIA	0.033	0.03	-10000	0	-0.42	2	2
IL17A	-0.03	0.26	-10000	0	-0.53	71	71
PI3K	-0.12	0.49	-10000	0	-1.1	73	73
IFNG	-0.007	0.049	0.15	5	-0.13	46	51
STAT3 (dimer)	-0.12	0.46	-10000	0	-1.1	72	72
IL18R1	0.015	0.09	-10000	0	-0.43	20	20
IL23/IL23R/JAK2/TYK2/SOCS3	-0.039	0.29	0.51	1	-0.67	47	48
IL18/IL18R	-0.011	0.16	-10000	0	-0.34	84	84
macrophage activation	-0.007	0.021	-10000	0	-0.044	59	59
TNF	-0.14	0.48	-10000	0	-1.2	69	69
STAT3/STAT4	-0.14	0.49	-10000	0	-1.2	72	72
STAT4 (dimer)	-0.14	0.52	-10000	0	-1.2	73	73
IL18	-0.001	0.11	-10000	0	-0.43	32	32
IL19	-0.082	0.46	-10000	0	-1.1	58	58
STAT5A (dimer)	-0.15	0.49	-10000	0	-1.2	69	69
STAT1	0.02	0.075	-10000	0	-0.42	14	14
SOCS3	0.028	0.046	-10000	0	-0.42	5	5
CXCL9	-0.21	0.57	-10000	0	-1.2	109	109
MPO	-0.1	0.45	-10000	0	-1.1	65	65
positive regulation of humoral immune response	-0.14	0.52	-10000	0	-1.2	70	70
IL23/IL23R/JAK2/TYK2	-0.16	0.56	-10000	0	-1.3	70	70
IL6	-0.18	0.56	-10000	0	-1.3	90	90
STAT5A	0.028	0.037	-10000	0	-0.42	3	3
IL2	0.029	0.039	-10000	0	-0.42	3	3
positive regulation of tyrosine phosphorylation of STAT protein	0.001	0.012	0.081	7	-10000	0	7
CD3E	-0.11	0.45	-10000	0	-1.1	65	65
keratinocyte proliferation	-0.14	0.52	-10000	0	-1.2	70	70
NOS2	-0.12	0.45	-10000	0	-1	70	70

×

Nongenotropic Androgen 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
PTK2	0.006	0.004	-10000	0	-10000	0	0
GNB1/GNG2	0.006	0.12	-10000	0	-0.24	102	102
regulation of S phase of mitotic cell cycle	-0.027	0.11	-10000	0	-0.23	101	101
GNAO1	0.029	0.014	-10000	0	-10000	0	0
HRAS	0.031	0.036	-10000	0	-0.42	3	3
SHBG/T-DHT	0.021	0.008	-10000	0	-10000	0	0
PELP1	0.032	0.011	-10000	0	-10000	0	0
AKT1	0.007	0.024	-10000	0	-0.3	3	3
MAP2K1	-0.054	0.098	0.17	18	-0.23	85	103
T-DHT/AR	-0.037	0.13	-10000	0	-0.3	99	99
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-0.006	70	70
GNAI2	0.027	0.058	-10000	0	-0.42	8	8
GNAI3	0.035	0.006	-10000	0	-10000	0	0
GNAI1	0.017	0.085	-10000	0	-0.42	18	18
mol:GDP	-0.072	0.15	-10000	0	-0.37	101	101
cell proliferation	-0.075	0.17	0.26	1	-0.44	73	74
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
FOS	-0.12	0.28	-10000	0	-0.79	73	73
mol:Ca2+	-0.009	0.023	-10000	0	-0.063	56	56
MAPK3	-0.06	0.14	0.26	3	-0.34	69	72
MAPK1	-0.044	0.12	-10000	0	-0.41	29	29
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
mol:IP3	0	0.002	-10000	0	-0.004	71	71
cAMP biosynthetic process	0.003	0.017	-10000	0	-10000	0	0
GNG2	0.034	0.021	-10000	0	-0.42	1	1
potassium channel inhibitor activity	0	0.002	-10000	0	-0.004	71	71
HRAS/GTP	-0.007	0.12	-10000	0	-0.22	97	97
actin cytoskeleton reorganization	0.038	0.052	-10000	0	-0.21	18	18
SRC	0.032	0.03	-10000	0	-0.42	2	2
voltage-gated calcium channel activity	0	0.002	-10000	0	-0.004	71	71
PI3K	0.032	0.057	-10000	0	-0.25	18	18
apoptosis	0.063	0.17	0.43	77	-10000	0	77
T-DHT/AR/PELP1	-0.016	0.12	-10000	0	-0.26	99	99
HRAS/GDP	-0.051	0.16	-10000	0	-0.36	102	102
CREB1	-0.071	0.18	-10000	0	-0.47	76	76
RAC1-CDC42/GTP	0.049	0.057	-10000	0	-0.21	18	18
AR	-0.054	0.18	-10000	0	-0.42	99	99
GNB1	0.032	0.045	-10000	0	-0.42	5	5
RAF1	-0.039	0.1	0.18	19	-0.22	93	112
RAC1-CDC42/GDP	-0.03	0.16	-10000	0	-0.35	96	96
T-DHT/AR/PELP1/Src	0.001	0.12	-10000	0	-0.24	96	96
MAP2K2	-0.056	0.099	0.17	19	-0.23	86	105
T-DHT/AR/PELP1/Src/PI3K	-0.028	0.11	-10000	0	-0.23	101	101
GNAZ	0.024	0.067	-10000	0	-0.42	11	11
SHBG	0.032	0.012	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.038	0.14	-10000	0	-0.42	38	38
mol:T-DHT	0	0.001	0.002	1	-0.004	16	17
RAC1	0.035	0.006	-10000	0	-10000	0	0
GNRH1	0.005	0.02	-10000	0	-0.3	2	2
Gi family/GTP	-0.029	0.086	-10000	0	-0.24	45	45
CDC42	0.034	0.008	-10000	0	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.074	0.28	-10000	0	-0.77	41	41
CRP	-0.043	0.3	0.56	3	-0.73	48	51
cell cycle arrest	-0.096	0.34	0.49	1	-0.79	68	69
TIMP1	-0.069	0.3	-10000	0	-0.77	54	54
IL6ST	-0.049	0.17	-10000	0	-0.42	88	88
Rac1/GDP	-0.051	0.19	0.29	2	-0.41	68	70
AP1	0.011	0.18	-10000	0	-0.54	22	22
GAB2	0.032	0.014	-10000	0	-10000	0	0
TNFSF11	-0.14	0.4	0.46	1	-0.94	85	86
HSP90B1	0	0.12	-10000	0	-0.83	8	8
GAB1	0.028	0.061	-10000	0	-0.42	9	9
MAPK14	-0.048	0.17	-10000	0	-0.52	33	33
AKT1	0.029	0.08	-10000	0	-0.48	3	3
FOXO1	0.037	0.081	0.35	1	-0.45	3	4
MAP2K6	-0.054	0.16	0.24	1	-0.42	56	57
mol:GTP	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.061	0.21	0.33	2	-0.46	73	75
MITF	-0.055	0.17	-10000	0	-0.38	75	75
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.035	0.005	-10000	0	-10000	0	0
A2M	-0.056	0.33	-10000	0	-1.3	33	33
CEBPB	0.027	0.051	-10000	0	-0.42	6	6
GRB2/SOS1/GAB family/SHP2	0.005	0.12	0.3	1	-0.44	18	19
STAT3	-0.11	0.37	0.5	1	-0.87	68	69
STAT1	-0.011	0.17	-10000	0	-0.88	17	17
CEBPD	-0.099	0.37	-10000	0	-0.91	69	69
PIK3CA	0.034	0.022	-10000	0	-0.42	1	1
PI3K	0.037	0.067	-10000	0	-0.3	18	18
JUN	-0.001	0.12	-10000	0	-0.42	39	39
PIAS3/MITF	-0.046	0.17	0.29	1	-0.39	63	64
MAPK11	-0.046	0.16	-10000	0	-0.52	33	33
STAT3 (dimer)/FOXO1	-0.054	0.28	0.56	2	-0.65	55	57
GRB2/SOS1/GAB family	-0.017	0.17	0.29	1	-0.44	36	37
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.064	0.17	-10000	0	-0.31	118	118
GRB2	0.034	0.011	-10000	0	-10000	0	0
JAK2	0.031	0.03	-10000	0	-0.42	2	2
LBP	-0.032	0.24	0.45	1	-0.58	44	45
PIK3R1	0.019	0.083	-10000	0	-0.42	17	17
JAK1	0.031	0.039	-10000	0	-0.42	3	3
MYC	-0.066	0.36	0.59	2	-0.9	61	63
FGG	-0.077	0.29	-10000	0	-0.75	48	48
macrophage differentiation	-0.096	0.34	0.49	1	-0.79	68	69
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.025	0.16	-10000	0	-0.26	136	136
JUNB	-0.076	0.28	-10000	0	-0.72	50	50
FOS	-0.031	0.15	-10000	0	-0.42	66	66
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.062	0.17	-10000	0	-0.39	75	75
STAT1/PIAS1	-0.047	0.19	0.3	1	-0.41	69	70
GRB2/SOS1/GAB family/SHP2/PI3K	0.03	0.081	-10000	0	-0.37	8	8
STAT3 (dimer)	-0.1	0.37	0.49	1	-0.85	68	69
PRKCD	-0.073	0.24	0.36	1	-0.54	75	76
IL6R	0.02	0.06	-10000	0	-0.43	8	8
SOCS3	-0.044	0.19	0.43	2	-0.79	16	18
gp130 (dimer)/JAK1/JAK1/LMO4	-0.028	0.15	-10000	0	-0.26	136	136
Rac1/GTP	-0.054	0.2	0.29	2	-0.43	72	74
HCK	0.017	0.087	-10000	0	-0.42	19	19
MAPKKK cascade	0.021	0.14	-10000	0	-0.57	16	16
bone resorption	-0.13	0.37	0.46	1	-0.86	86	87
IRF1	-0.092	0.32	-10000	0	-0.83	55	55
mol:GDP	-0.058	0.18	-10000	0	-0.4	76	76
SOS1	0.036	0.022	-10000	0	-0.42	1	1
VAV1	-0.059	0.18	-10000	0	-0.4	77	77
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.045	0.19	0.33	1	-0.51	41	42
PTPN11	0.016	0.091	-10000	0	-1.1	3	3
IL6/IL6RA	0.003	0.1	-10000	0	-0.3	48	48
gp130 (dimer)/TYK2/TYK2/LMO4	-0.024	0.14	-10000	0	-0.26	135	135
gp130 (dimer)/JAK2/JAK2/LMO4	-0.026	0.15	-10000	0	-0.26	135	135
IL6	-0.022	0.14	-10000	0	-0.43	53	53
PIAS3	0.035	0.006	-10000	0	-10000	0	0
PTPRE	0.021	0.064	-10000	0	-0.41	10	10
PIAS1	0.035	0.006	-10000	0	-10000	0	0
RAC1	0.035	0.006	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.056	0.13	-10000	0	-0.26	134	134
LMO4	-0.02	0.14	-10000	0	-0.42	54	54
STAT3 (dimer)/PIAS3	-0.091	0.34	-10000	0	-0.8	64	64
MCL1	0.037	0.094	-10000	0	-0.78	2	2

×

FAS signaling pathway (CD95)

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
SPTAN1	0.024	0.084	0.2	75	-10000	0	75
RFC1	0.02	0.076	0.19	70	-10000	0	70
PRKDC	0.044	0.1	0.22	111	-0.23	1	112
RIPK1	0.035	0.008	-10000	0	-10000	0	0
CASP7	-0.007	0.14	-10000	0	-0.69	18	18
FASLG/FAS/FADD/FAF1	0.004	0.093	0.2	40	-0.26	28	68
MAP2K4	-0.025	0.17	0.44	2	-0.46	42	44
mol:ceramide	-0.013	0.11	-10000	0	-0.36	33	33
GSN	0.018	0.088	0.2	73	-0.24	9	82
FASLG/FAS/FADD/FAF1/Caspase 8	0.007	0.11	0.23	4	-0.33	28	32
FAS	0.003	0.1	-10000	0	-0.42	28	28
BID	-0.018	0.053	0.26	12	-0.27	7	19
MAP3K1	-0.011	0.14	0.3	4	-0.48	22	26
MAP3K7	0.032	0.01	-10000	0	-10000	0	0
RB1	0.019	0.073	0.19	62	-0.23	1	63
CFLAR	0.032	0.046	-10000	0	-0.42	5	5
HGF/MET	0.015	0.12	-10000	0	-0.27	78	78
ARHGDIB	0.016	0.092	0.2	70	-0.25	13	83
FADD	0.024	0.021	-10000	0	-10000	0	0
actin filament polymerization	-0.017	0.089	0.24	11	-0.2	71	82
NFKB1	0.003	0.1	-10000	0	-0.63	8	8
MAPK8	-0.044	0.21	0.51	2	-0.5	67	69
DFFA	0.022	0.08	0.2	71	-10000	0	71
DNA fragmentation during apoptosis	0.022	0.081	0.2	71	-0.2	1	72
FAS/FADD/MET	0.032	0.079	-10000	0	-0.26	28	28
CFLAR/RIP1	0.048	0.038	-10000	0	-0.3	5	5
FAIM3	0.015	0.078	-10000	0	-0.42	15	15
FAF1	0.028	0.03	-10000	0	-0.42	1	1
PARP1	0.028	0.097	0.22	79	-0.24	3	82
DFFB	0.022	0.081	0.2	74	-0.2	1	75
CHUK	-0.007	0.1	-10000	0	-0.55	10	10
FASLG	-0.009	0.11	-10000	0	-0.43	34	34
FAS/FADD	0.02	0.077	-10000	0	-0.31	23	23
HGF	0.028	0.057	-10000	0	-0.42	8	8
LMNA	0.022	0.096	0.32	25	-0.22	6	31
CASP6	0.019	0.081	0.19	68	-0.22	4	72
CASP10	0.029	0.02	-10000	0	-10000	0	0
CASP3	0.032	0.094	0.24	81	-0.22	6	87
PTPN13	-0.031	0.16	-10000	0	-0.42	72	72
CASP8	-0.013	0.057	0.33	13	-10000	0	13
IL6	-0.1	0.41	-10000	0	-1.2	60	60
MET	0.029	0.046	-10000	0	-0.42	5	5
ICAD/CAD	0.019	0.073	0.38	4	-10000	0	4
FASLG/FAS/FADD/FAF1/Caspase 10	-0.013	0.11	-10000	0	-0.36	33	33
activation of caspase activity by cytochrome c	-0.017	0.053	0.26	12	-0.27	7	19
PAK2	0.021	0.078	0.19	71	-0.2	1	72
BCL2	-0.057	0.18	-10000	0	-0.42	99	99

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.03	0.037	-10000	0	-0.42	3	3
GNB1/GNG2	-0.05	0.17	-10000	0	-0.38	62	62
mol:DAG	-0.059	0.15	-10000	0	-0.35	60	60
PLCG1	-0.061	0.15	-10000	0	-0.36	60	60
YES1	-0.067	0.15	-10000	0	-0.4	57	57
FZD3	0.006	0.097	-10000	0	-0.42	24	24
FZD6	-0.03	0.15	-10000	0	-0.42	61	61
G protein	-0.036	0.17	0.29	11	-0.37	56	67
MAP3K7	-0.058	0.12	0.24	3	-0.32	54	57
mol:Ca2+	-0.056	0.14	-10000	0	-0.34	60	60
mol:IP3	-0.059	0.15	-10000	0	-0.35	60	60
NLK	-0.035	0.25	-10000	0	-0.82	45	45
GNB1	0.032	0.045	-10000	0	-0.42	5	5
CAMK2A	-0.058	0.14	0.25	3	-0.33	57	60
MAP3K7IP1	0.034	0.009	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.071	0.15	-10000	0	-0.41	57	57
CSNK1A1	0.035	0.005	-10000	0	-10000	0	0
GNAS	-0.065	0.15	-10000	0	-0.39	55	55
GO:0007205	-0.06	0.14	0.26	3	-0.35	58	61
WNT6	0.03	0.031	-10000	0	-0.42	2	2
WNT4	-0.019	0.14	-10000	0	-0.42	58	58
NFAT1/CK1 alpha	-0.049	0.16	0.29	2	-0.38	53	55
GNG2	0.034	0.021	-10000	0	-0.42	1	1
WNT5A	-0.027	0.15	-10000	0	-0.42	64	64
WNT11	0.027	0.032	-10000	0	-0.42	2	2
CDC42	-0.065	0.15	-10000	0	-0.4	54	54

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.013	0.083	-10000	0	-0.22	66	66
epithelial cell differentiation	0.025	0.093	-10000	0	-0.22	56	56
CYFIP2	-0.006	0.13	-10000	0	-0.42	44	44
ENAH	-0.027	0.079	0.33	4	-0.31	8	12
EGFR	-0.013	0.13	-10000	0	-0.42	47	47
EPHA2	0.031	0.036	-10000	0	-0.42	3	3
MYO6	-0.037	0.078	0.18	1	-0.22	63	64
CTNNB1	0.024	0.067	-10000	0	-0.42	11	11
ABI1/Sra1/Nap1	0.041	0.089	-10000	0	-0.26	39	39
AQP5	-0.095	0.17	-10000	0	-0.45	83	83
CTNND1	0.034	0.022	-10000	0	-0.42	1	1
mol:PI-4-5-P2	-0.032	0.07	-10000	0	-0.21	53	53
regulation of calcium-dependent cell-cell adhesion	-0.032	0.069	-10000	0	-0.21	54	54
EGF	-0.069	0.19	-10000	0	-0.42	110	110
NCKAP1	0.034	0.021	-10000	0	-0.42	1	1
AQP3	-0.095	0.17	-10000	0	-0.46	83	83
cortical microtubule organization	0.025	0.093	-10000	0	-0.22	56	56
GO:0000145	-0.034	0.065	-10000	0	-0.2	53	53
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.03	0.096	-10000	0	-0.22	56	56
MLLT4	0.02	0.075	-10000	0	-0.42	14	14
ARF6/GDP	-0.042	0.068	-10000	0	-0.28	16	16
ARF6	0.033	0.029	-10000	0	-0.42	2	2
Ephrin A1/EPHA2/NCK1/GIT1	0.052	0.072	-10000	0	-0.24	20	20
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.027	0.093	-10000	0	-0.37	14	14
PVRL2	0.026	0.064	-10000	0	-0.42	10	10
ZYX	-0.034	0.074	-10000	0	-0.22	57	57
ARF6/GTP	0.058	0.077	-10000	0	-0.24	20	20
CDH1	-0.012	0.13	-10000	0	-0.42	45	45
EGFR/EGFR/EGF/EGF	-0.057	0.14	-10000	0	-0.22	189	189
RhoA/GDP	0.022	0.099	-10000	0	-0.22	63	63
actin cytoskeleton organization	-0.041	0.074	-10000	0	-0.22	51	51
IGF-1R heterotetramer	-0.043	0.17	-10000	0	-0.42	84	84
GIT1	0.033	0.022	-10000	0	-0.42	1	1
IGF1R	-0.043	0.17	-10000	0	-0.42	84	84
IGF1	-0.041	0.17	-10000	0	-0.42	80	80
DIAPH1	0.002	0.2	-10000	0	-0.59	36	36
Wnt receptor signaling pathway	-0.025	0.093	0.22	56	-10000	0	56
RHOA	0.026	0.061	-10000	0	-0.42	9	9
RhoA/GTP	-0.044	0.069	-10000	0	-0.22	58	58
CTNNA1	0.035	0.006	-10000	0	-10000	0	0
VCL	-0.042	0.075	-10000	0	-0.23	51	51
EFNA1	0.014	0.08	-10000	0	-0.42	16	16
LPP	-0.039	0.071	-10000	0	-0.3	2	2
Ephrin A1/EPHA2	0.009	0.092	-10000	0	-0.22	57	57
SEC6/SEC8	-0.049	0.068	-10000	0	-0.21	65	65
MGAT3	-0.033	0.069	-10000	0	-0.21	54	54
HGF/MET	0.015	0.093	-10000	0	-0.21	66	66
HGF	0.028	0.057	-10000	0	-0.42	8	8
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.013	0.083	-10000	0	-0.22	66	66
actin cable formation	0.015	0.11	0.26	14	-0.31	8	22
KIAA1543	-0.037	0.069	-10000	0	-0.22	53	53
KIFC3	-0.032	0.067	-10000	0	-0.21	50	50
NCK1	0.034	0.022	-10000	0	-0.42	1	1
EXOC3	0.036	0.002	-10000	0	-10000	0	0
ACTN1	-0.034	0.074	-10000	0	-0.22	56	56
NCK1/GIT1	0.048	0.025	-10000	0	-0.3	2	2
mol:GDP	0.025	0.093	-10000	0	-0.22	56	56
EXOC4	0.034	0.021	-10000	0	-0.42	1	1
STX4	-0.034	0.062	-10000	0	-0.21	56	56
PIP5K1C	-0.032	0.07	-10000	0	-0.22	53	53
LIMA1	0	0	-10000	0	-10000	0	0
ABI1	0.034	0.008	-10000	0	-10000	0	0
ROCK1	-0.008	0.1	0.33	7	-0.33	7	14
adherens junction assembly	-0.045	0.12	0.26	1	-0.48	15	16
IGF-1R heterotetramer/IGF1	-0.057	0.15	-10000	0	-0.24	176	176
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.032	0.074	-10000	0	-0.3	23	23
MET	0.029	0.046	-10000	0	-0.42	5	5
PLEKHA7	-0.031	0.07	0.18	1	-0.21	55	56
mol:GTP	0.05	0.07	-10000	0	-0.23	20	20
establishment of epithelial cell apical/basal polarity	-0.044	0.072	0.15	1	-0.32	3	4
cortical actin cytoskeleton stabilization	-0.013	0.083	-10000	0	-0.22	66	66
regulation of cell-cell adhesion	-0.041	0.074	-10000	0	-0.22	51	51
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.013	0.083	-10000	0	-0.22	66	66

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.026	0.18	-10000	0	-0.45	62	62
Syndecan-4/Syndesmos	-0.031	0.2	-10000	0	-0.5	61	61
positive regulation of JNK cascade	-0.044	0.22	-10000	0	-0.48	78	78
Syndecan-4/ADAM12	-0.049	0.23	-10000	0	-0.51	80	80
CCL5	-0.013	0.14	-10000	0	-0.42	51	51
Rac1/GDP	0.026	0.004	-10000	0	-10000	0	0
DNM2	0.035	0.005	-10000	0	-10000	0	0
ITGA5	0.033	0.035	-10000	0	-0.42	3	3
SDCBP	0.022	0.061	-10000	0	-0.42	9	9
PLG	0.021	0.04	-10000	0	-0.31	3	3
ADAM12	-0.012	0.14	-10000	0	-0.42	51	51
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.028	0.046	-10000	0	-0.42	5	5
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.032	0.02	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.032	0.21	-10000	0	-0.5	66	66
Syndecan-4/CXCL12/CXCR4	-0.047	0.23	-10000	0	-0.51	78	78
Syndecan-4/Laminin alpha3	-0.054	0.22	-10000	0	-0.51	68	68
MDK	0.017	0.085	-10000	0	-0.42	18	18
Syndecan-4/FZD7	-0.05	0.22	-10000	0	-0.5	76	76
Syndecan-4/Midkine	-0.038	0.21	-10000	0	-0.5	67	67
FZD7	-0.007	0.13	-10000	0	-0.42	44	44
Syndecan-4/FGFR1/FGF	-0.033	0.2	-10000	0	-0.47	63	63
THBS1	0.001	0.12	-10000	0	-0.42	37	37
integrin-mediated signaling pathway	-0.041	0.21	-10000	0	-0.48	76	76
positive regulation of MAPKKK cascade	-0.044	0.22	-10000	0	-0.48	78	78
Syndecan-4/TACI	-0.033	0.21	-10000	0	-0.5	66	66
CXCR4	0.006	0.11	-10000	0	-0.42	31	31
cell adhesion	0.012	0.099	0.2	46	-0.27	40	86
Syndecan-4/Dynamin	-0.029	0.21	-10000	0	-0.49	66	66
Syndecan-4/TSP1	-0.043	0.22	-10000	0	-0.49	75	75
Syndecan-4/GIPC	-0.03	0.21	-10000	0	-0.49	66	66
Syndecan-4/RANTES	-0.05	0.22	-10000	0	-0.51	70	70
ITGB1	0.033	0.03	-10000	0	-0.42	2	2
LAMA1	0.034	0.009	-10000	0	-10000	0	0
LAMA3	-0.019	0.14	-10000	0	-0.42	57	57
RAC1	0.035	0.006	-10000	0	-10000	0	0
PRKCA	0.09	0.26	0.79	59	-10000	0	59
Syndecan-4/alpha-Actinin	-0.033	0.22	-10000	0	-0.51	67	67
TFPI	0.034	0.008	-10000	0	-10000	0	0
F2	0.031	0.025	-10000	0	-10000	0	0
alpha5/beta1 Integrin	0.047	0.037	-10000	0	-0.3	5	5
positive regulation of cell adhesion	-0.06	0.2	-10000	0	-0.5	68	68
ACTN1	0.026	0.061	-10000	0	-0.42	9	9
TNC	0.004	0.11	-10000	0	-0.42	31	31
Syndecan-4/CXCL12	-0.048	0.22	-10000	0	-0.5	76	76
FGF6	0.026	0.058	-10000	0	-0.42	8	8
RHOA	0.026	0.061	-10000	0	-0.42	9	9
CXCL12	-0.007	0.13	-10000	0	-0.42	46	46
TNFRSF13B	0.032	0.012	-10000	0	-10000	0	0
FGF2	-0.001	0.11	-10000	0	-0.42	34	34
FGFR1	0.021	0.061	-10000	0	-0.42	9	9
Syndecan-4/PI-4-5-P2	-0.059	0.19	-10000	0	-0.49	66	66
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.019	0.13	-10000	0	-0.41	48	48
cell migration	-0.015	0.015	-10000	0	-10000	0	0
PRKCD	0.022	0.04	-10000	0	-0.3	3	3
vasculogenesis	-0.041	0.21	-10000	0	-0.47	75	75
SDC4	-0.059	0.2	-10000	0	-0.52	66	66
Syndecan-4/Tenascin C	-0.044	0.22	-10000	0	-0.5	75	75
Syndecan-4/PI-4-5-P2/PKC alpha	-0.026	0.016	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.034	0.2	-10000	0	-0.5	60	60
MMP9	-0.014	0.14	-10000	0	-0.42	52	52
Rac1/GTP	0.012	0.1	0.2	46	-0.27	40	86
cytoskeleton organization	-0.029	0.2	-10000	0	-0.48	61	61
GIPC1	0.033	0.035	-10000	0	-0.42	3	3
Syndecan-4/TFPI	-0.033	0.21	-10000	0	-0.5	66	66

×

Wnt 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
Noncanonical Wnts/FZD	-0.071	0.15	-9999	-0.41	57	57
FZD6	-0.03	0.15	-9999	-0.42	61	61
WNT6	0.03	0.031	-9999	-0.42	2	2
WNT4	-0.019	0.14	-9999	-0.42	58	58
FZD3	0.006	0.097	-9999	-0.42	24	24
WNT5A	-0.027	0.15	-9999	-0.42	64	64
WNT11	0.027	0.032	-9999	-0.42	2	2

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.032	0.071	-10000	0	-0.22	32	32
NF kappa B1 p50/RelA/I kappa B alpha	0.021	0.096	0.27	6	-0.31	9	15
AP1	-0.034	0.12	-10000	0	-0.25	101	101
mol:PIP3	-0.03	0.09	-10000	0	-0.22	85	85
AKT1	-0.006	0.1	0.25	3	-0.31	28	31
PTK2B	-0.041	0.1	0.14	1	-0.21	110	111
RHOA	-0.015	0.1	-10000	0	-0.34	32	32
PIK3CB	0.031	0.046	-10000	0	-0.42	5	5
mol:Ca2+	-0.009	0.092	0.19	44	-0.2	53	97
MAGI3	0.012	0.099	-10000	0	-0.42	25	25
RELA	0.035	0.006	-10000	0	-10000	0	0
apoptosis	0.004	0.052	-10000	0	-0.18	36	36
HRAS/GDP	0.024	0.025	-10000	0	-0.3	3	3
positive regulation of microtubule depolymerization	-0.076	0.12	0.18	3	-0.24	127	130
NF kappa B1 p50/RelA	-0.021	0.082	-10000	0	-0.22	57	57
endothelial cell migration	-0.008	0.12	-10000	0	-0.52	25	25
ADCY4	-0.014	0.086	-10000	0	-0.28	37	37
ADCY5	-0.014	0.083	-10000	0	-0.28	33	33
ADCY6	-0.012	0.08	-10000	0	-0.26	35	35
ADCY7	-0.013	0.085	-10000	0	-0.29	32	32
ADCY1	-0.012	0.081	-10000	0	-0.27	36	36
ADCY2	-0.024	0.097	-10000	0	-0.3	41	41
ADCY3	-0.013	0.081	-10000	0	-0.27	34	34
ADCY8	-0.012	0.072	-10000	0	-0.27	27	27
ADCY9	-0.015	0.08	-10000	0	-0.24	42	42
GSK3B	-0.042	0.097	0.16	1	-0.21	105	106
arachidonic acid secretion	-0.017	0.088	-10000	0	-0.27	44	44
GNG2	0.034	0.021	-10000	0	-0.42	1	1
TRIP6	0.008	0.071	-10000	0	-0.36	17	17
GNAO1	0.006	0.053	-10000	0	-0.22	25	25
HRAS	0.032	0.036	-10000	0	-0.42	3	3
NFKBIA	-0.008	0.092	0.21	14	-0.26	19	33
GAB1	0.027	0.061	-10000	0	-0.42	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.023	0.2	-10000	0	-0.92	21	21
JUN	-0.001	0.12	-10000	0	-0.42	39	39
LPA/LPA2/NHERF2	-0.004	0.077	-10000	0	-0.2	57	57
TIAM1	0.002	0.23	-10000	0	-1.1	21	21
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
mol:IP3	-0.008	0.092	0.18	47	-0.21	50	97
PLCB3	0.01	0.091	0.19	47	-0.23	42	89
FOS	-0.031	0.15	-10000	0	-0.42	66	66
positive regulation of mitosis	-0.017	0.088	-10000	0	-0.27	44	44
LPA/LPA1-2-3	-0.006	0.049	-10000	0	-0.17	39	39
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.029	0.014	-10000	0	-10000	0	0
stress fiber formation	-0.006	0.081	-10000	0	-0.28	21	21
GNAZ	0	0.069	-10000	0	-0.21	46	46
EGFR/PI3K-beta/Gab1	-0.022	0.097	-10000	0	-0.22	85	85
positive regulation of dendritic cell cytokine production	-0.006	0.048	-10000	0	-0.17	39	39
LPA/LPA2/MAGI-3	0.005	0.065	-10000	0	-0.17	49	49
ARHGEF1	0.026	0.076	0.19	51	-0.21	22	73
GNAI2	0.002	0.07	-10000	0	-0.22	41	41
GNAI3	0.007	0.056	-10000	0	-0.19	35	35
GNAI1	-0.004	0.08	-10000	0	-0.23	51	51
LPA/LPA3	-0.004	0.025	-10000	0	-0.086	39	39
LPA/LPA2	-0.004	0.024	-10000	0	-0.086	39	39
LPA/LPA1	-0.009	0.065	-10000	0	-0.23	39	39
HB-EGF/EGFR	-0.025	0.12	-10000	0	-0.28	89	89
HBEGF	-0.021	0.098	-10000	0	-0.3	55	55
mol:DAG	-0.008	0.092	0.18	47	-0.21	50	97
cAMP biosynthetic process	-0.019	0.088	0.2	3	-0.27	37	40
NFKB1	0.035	0.005	-10000	0	-10000	0	0
SRC	0.032	0.03	-10000	0	-0.42	2	2
GNB1	0.032	0.045	-10000	0	-0.42	5	5
LYN	0.006	0.095	0.2	45	-0.24	19	64
GNAQ	-0.003	0.02	-10000	0	-0.07	39	39
LPAR2	0	0.001	-10000	0	-10000	0	0
LPAR3	0	0	-10000	0	-10000	0	0
LPAR1	-0.007	0.038	-10000	0	-0.14	39	39
IL8	-0.069	0.18	-10000	0	-0.42	86	86
PTK2	0.011	0.042	-10000	0	-0.16	25	25
Rac1/GDP	0.026	0.004	-10000	0	-10000	0	0
CASP3	0.004	0.053	-10000	0	-0.18	36	36
EGFR	-0.013	0.13	-10000	0	-0.42	47	47
PLCG1	-0.003	0.043	-10000	0	-0.12	48	48
PLD2	0.01	0.052	-10000	0	-0.17	36	36
G12/G13	0.031	0.063	-10000	0	-0.22	22	22
PI3K-beta	-0.019	0.1	-10000	0	-0.34	28	28
cell migration	0.009	0.067	-10000	0	-0.26	20	20
SLC9A3R2	-0.004	0.12	-10000	0	-0.42	40	40
PXN	-0.006	0.082	-10000	0	-0.28	21	21
HRAS/GTP	-0.017	0.09	-10000	0	-0.28	44	44
RAC1	0.035	0.006	-10000	0	-10000	0	0
MMP9	-0.014	0.14	-10000	0	-0.42	52	52
PRKCE	0.031	0.046	-10000	0	-0.42	5	5
PRKCD	-0.011	0.089	0.18	43	-0.21	42	85
Gi(beta/gamma)	-0.007	0.085	-10000	0	-0.26	38	38
mol:LPA	-0.007	0.038	-10000	0	-0.14	39	39
TRIP6/p130 Cas/FAK1/Paxillin	0.009	0.08	-10000	0	-0.26	23	23
MAPKKK cascade	-0.017	0.088	-10000	0	-0.27	44	44
contractile ring contraction involved in cytokinesis	-0.016	0.1	-10000	0	-0.34	34	34
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.015	0.075	-10000	0	-0.21	55	55
GNA15	0.007	0.035	-10000	0	-0.12	24	24
GNA12	0.035	0.006	-10000	0	-10000	0	0
GNA13	0.028	0.042	-10000	0	-0.42	4	4
MAPT	-0.078	0.12	0.18	3	-0.25	127	130
GNA11	0.008	0.03	-10000	0	-0.25	3	3
Rac1/GTP	0.023	0.21	-10000	0	-0.98	21	21
MMP2	-0.008	0.12	-10000	0	-0.52	25	25

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.015	0.032	-10000	0	-0.25	6	6
ARNO/beta Arrestin1-2	0.013	0.069	-10000	0	-0.2	40	40
EGFR	-0.013	0.13	-10000	0	-0.42	47	47
EPHA2	0.031	0.036	-10000	0	-0.42	3	3
USP6	0.032	0.012	-10000	0	-10000	0	0
IQSEC1	0.034	0.021	-10000	0	-0.42	1	1
EGFR/EGFR/EGF/EGF	-0.061	0.16	-10000	0	-0.31	151	151
ARRB2	0.011	0.043	-10000	0	-0.3	9	9
mol:GTP	0.007	0.019	0.11	5	-0.11	2	7
ARRB1	0.026	0.05	-10000	0	-0.42	6	6
FBXO8	0.035	0.007	-10000	0	-10000	0	0
TSHR	0.029	0.05	-10000	0	-0.42	6	6
EGF	-0.069	0.19	-10000	0	-0.42	110	110
somatostatin receptor activity	0	0	0	3	-0.001	75	78
ARAP2	0	0	0	2	0	68	70
mol:GDP	-0.029	0.099	-10000	0	-0.25	57	57
mol:PI-3-4-5-P3	0	0	0	2	-0.001	73	75
ITGA2B	0.034	0.009	-10000	0	-10000	0	0
ARF6	0.033	0.029	-10000	0	-0.42	2	2
Ephrin A1/EPHA2/NCK1/GIT1	0.052	0.072	-10000	0	-0.24	20	20
ADAP1	0	0	0	2	0	44	46
KIF13B	0.022	0.051	-10000	0	-0.42	6	6
HGF/MET	0.041	0.057	-10000	0	-0.3	13	13
PXN	0.036	0.004	-10000	0	-10000	0	0
ARF6/GTP	-0.035	0.1	0.15	2	-0.24	76	78
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.035	0.15	-10000	0	-0.26	150	150
ADRB2	0.003	0.11	-10000	0	-0.42	33	33
receptor agonist activity	0	0	0	2	0	54	56
actin filament binding	0	0	0	3	0	77	80
SRC	0.032	0.03	-10000	0	-0.42	2	2
ITGB3	0.029	0.046	-10000	0	-0.42	5	5
GNAQ	0	0	0.001	4	-0.001	54	58
EFA6/PI-4-5-P2	0	0	0.001	4	-0.001	51	55
ARF6/GDP	0.004	0.074	0.2	2	-0.27	12	14
ARF6/GDP/GULP/ACAP1	-0.017	0.12	-10000	0	-0.27	71	71
alphaIIb/beta3 Integrin/paxillin/GIT1	0.079	0.042	-10000	0	-0.24	5	5
ACAP1	0	0	0	1	-10000	0	1
ACAP2	0	0	0	1	0	70	71
LHCGR/beta Arrestin2	0.018	0.06	-10000	0	-0.38	9	9
EFNA1	0.014	0.08	-10000	0	-0.42	16	16
HGF	0.028	0.057	-10000	0	-0.42	8	8
CYTH3	0	0	0.001	3	-0.001	61	64
CYTH2	-0.001	0.002	-10000	0	-0.004	80	80
NCK1	0.034	0.022	-10000	0	-0.42	1	1
fibronectin binding	0	0	0	2	0	52	54
endosomal lumen acidification	0	0	0	2	0	62	64
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	0.001	0.12	-10000	0	-0.42	37	37
GNAQ/ARNO	-0.001	0.003	0.006	4	-0.006	52	56
mol:Phosphatidic acid	0	0	0	1	0	70	71
PIP3-E	0.028	0.042	-10000	0	-0.42	4	4
MET	0.028	0.046	-10000	0	-0.42	5	5
GNA14	-0.01	0.13	-10000	0	-0.42	44	44
GNA15	0.029	0.046	-10000	0	-0.42	5	5
GIT1	0.033	0.022	-10000	0	-0.42	1	1
mol:PI-4-5-P2	0	0	0.001	2	-0.001	56	58
GNA11	0.032	0.036	-10000	0	-0.42	3	3
LHCGR	0.027	0.061	-10000	0	-0.42	9	9
AGTR1	-0.045	0.16	-10000	0	-0.42	78	78
desensitization of G-protein coupled receptor protein signaling pathway	0.018	0.06	-10000	0	-0.38	9	9
IPCEF1/ARNO	-0.024	0.12	-10000	0	-0.2	149	149
alphaIIb/beta3 Integrin	0.046	0.034	-10000	0	-0.3	4	4

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.019	0.075	-10000	0	-0.42	14	14
EPHB2	0.032	0.03	-10000	0	-0.43	2	2
EFNB1	0.013	0.032	-10000	0	-0.3	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.071	0.067	-10000	0	-0.24	17	17
Ephrin B2/EPHB1-2	0.045	0.064	-10000	0	-0.24	20	20
neuron projection morphogenesis	0.046	0.058	-10000	0	-0.23	17	17
Ephrin B1/EPHB1-2/Tiam1	0.062	0.066	-10000	0	-0.26	17	17
DNM1	0.032	0.041	-10000	0	-0.42	4	4
cell-cell signaling	0	0.003	-10000	0	-10000	0	0
MAP2K4	-0.08	0.2	0.23	1	-0.55	78	79
YES1	-0.11	0.3	-10000	0	-0.8	79	79
Ephrin B1/EPHB1-2/NCK2	0.067	0.054	-10000	0	-0.24	12	12
PI3K	-0.048	0.23	-10000	0	-0.56	79	79
mol:GDP	0.06	0.065	-10000	0	-0.25	17	17
ITGA2B	0.034	0.009	-10000	0	-10000	0	0
endothelial cell proliferation	0.023	0.076	-10000	0	-0.27	30	30
FYN	-0.11	0.3	-10000	0	-0.8	79	79
MAP3K7	-0.08	0.21	0.23	2	-0.59	75	77
FGR	-0.1	0.29	-10000	0	-0.78	79	79
TIAM1	0.028	0.057	-10000	0	-0.42	8	8
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
RGS3	0.035	0.005	-10000	0	-10000	0	0
cell adhesion	-0.056	0.21	-10000	0	-0.53	77	77
LYN	-0.1	0.29	-10000	0	-0.78	79	79
Ephrin B1/EPHB1-2/Src Family Kinases	-0.1	0.27	-10000	0	-0.73	79	79
Ephrin B1/EPHB1-2	-0.086	0.23	-10000	0	-0.64	75	75
SRC	-0.099	0.29	-10000	0	-0.78	78	78
ITGB3	0.029	0.046	-10000	0	-0.42	5	5
EPHB1	0.026	0.051	-10000	0	-0.42	6	6
EPHB4	0.018	0.085	-10000	0	-0.42	18	18
RAC1	0.035	0.006	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.023	0.076	-10000	0	-0.27	30	30
alphaIIb/beta3 Integrin	0.046	0.034	-10000	0	-0.3	4	4
BLK	-0.12	0.29	-10000	0	-0.8	78	78
HCK	-0.11	0.29	-10000	0	-0.78	78	78
regulation of stress fiber formation	-0.065	0.053	0.24	12	-10000	0	12
MAPK8	-0.079	0.2	-10000	0	-0.53	78	78
Ephrin B1/EPHB1-2/RGS3	0.067	0.054	-10000	0	-0.24	12	12
endothelial cell migration	-0.077	0.19	0.2	4	-0.5	75	79
NCK2	0.036	0.004	-10000	0	-10000	0	0
PTPN13	-0.046	0.2	-10000	0	-0.54	72	72
regulation of focal adhesion formation	-0.065	0.053	0.24	12	-10000	0	12
chemotaxis	-0.065	0.053	0.24	12	-10000	0	12
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
Rac1/GTP	0.06	0.063	-10000	0	-0.24	17	17
angiogenesis	-0.088	0.23	-10000	0	-0.63	78	78
LCK	-0.12	0.3	-10000	0	-0.8	79	79

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.017	0.036	-10000	0	-0.26	11	11
SNTA1	0.031	0.041	-10000	0	-0.42	4	4
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.022	0.05	-10000	0	-0.26	22	22
MAPK12	0.001	0.084	0.21	40	-0.23	33	73
CCND1	-0.056	0.16	-10000	0	-0.42	81	81
p38 gamma/SNTA1	0.026	0.088	0.34	2	-0.22	35	37
MAP2K3	0.032	0.023	-10000	0	-0.42	1	1
PKN1	0.033	0.035	-10000	0	-0.42	3	3
G2/M transition checkpoint	0.001	0.083	0.21	40	-0.23	33	73
MAP2K6	0.013	0.095	0.24	45	-0.24	33	78
MAPT	-0.055	0.13	0.28	5	-0.28	106	111
MAPK13	0.006	0.052	-10000	0	-0.3	14	14
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.005	0.062	-10000	0	-0.29	22	22

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.002	0.05	-10000	0	-0.3	14	14
TP53	-0.026	0.092	0.26	1	-0.26	61	62
Senescence	-0.029	0.094	0.26	1	-0.25	69	70
Apoptosis	-0.029	0.094	0.26	1	-0.25	69	70
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.004	0.061	0.26	25	-10000	0	25
MDM4	0.026	0.032	-10000	0	-0.42	2	2

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.013	0.1	-9999	-0.26	58	58
E-cadherin/beta catenin	0.004	0.11	-9999	-0.3	55	55
CTNNB1	0.024	0.067	-9999	-0.42	11	11
JUP	0.028	0.042	-9999	-0.42	4	4
CDH1	-0.012	0.13	-9999	-0.42	45	45

×

ErbB4 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.06	0.29	-10000	0	-0.93	46	46
epithelial cell differentiation	-0.028	0.25	-10000	0	-0.7	50	50
ITCH	0.035	0.038	-10000	0	-10000	0	0
WWP1	-0.087	0.39	-10000	0	-1.4	42	42
FYN	0.027	0.05	-10000	0	-0.42	6	6
EGFR	-0.013	0.13	-10000	0	-0.42	47	47
PRL	0.033	0.022	-10000	0	-0.42	1	1
neuron projection morphogenesis	-0.019	0.22	0.32	14	-0.65	43	57
PTPRZ1	0.023	0.058	-10000	0	-0.42	8	8
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.03	0.23	-10000	0	-0.72	43	43
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.064	0.26	-10000	0	-0.88	43	43
ADAM17	0.035	0.037	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.08	0.3	-10000	0	-1	45	45
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.062	0.29	-10000	0	-0.91	47	47
NCOR1	0.032	0.011	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.053	0.25	-10000	0	-0.82	43	43
GRIN2B	-0.062	0.22	0.25	1	-0.75	43	44
ErbB4/ErbB2/betacellulin	-0.07	0.26	-10000	0	-0.73	56	56
STAT1	0.02	0.075	-10000	0	-0.42	14	14
HBEGF	0.03	0.046	-10000	0	-0.42	5	5
PRLR	-0.002	0.12	-10000	0	-0.42	40	40
E4ICDs/ETO2	-0.11	0.32	-10000	0	-0.84	62	62
axon guidance	-0.069	0.28	-10000	0	-0.9	46	46
NEDD4	0.024	0.079	-10000	0	-0.43	12	12
Prolactin receptor/Prolactin receptor/Prolactin	0.022	0.095	-10000	0	-0.3	39	39
CBFA2T3	-0.047	0.16	-10000	0	-0.42	81	81
ErbB4/ErbB2/HBEGF	-0.051	0.26	-10000	0	-0.78	50	50
MAPK3	-0.016	0.22	0.35	9	-0.67	43	52
STAT1 (dimer)	-0.064	0.29	-10000	0	-0.91	47	47
MAPK1	-0.016	0.22	0.35	9	-0.67	43	52
JAK2	0.031	0.03	-10000	0	-0.42	2	2
ErbB4/ErbB2/neuregulin 1 beta	-0.064	0.25	-10000	0	-0.78	50	50
NRG1	0.012	0.021	-10000	0	-10000	0	0
NRG3	0.028	0.054	-10000	0	-0.42	7	7
NRG2	0.025	0.058	-10000	0	-0.42	8	8
NRG4	0.033	0.022	-10000	0	-0.42	1	1
heart development	-0.069	0.28	-10000	0	-0.9	46	46
neural crest cell migration	-0.063	0.25	-10000	0	-0.76	50	50
ERBB2	0.006	0.058	-10000	0	-0.3	15	15
WWOX/E4ICDs	-0.071	0.29	-10000	0	-0.91	47	47
SHC1	0.027	0.025	-10000	0	-0.42	1	1
ErbB4/EGFR/neuregulin 4	-0.065	0.28	-10000	0	-0.84	48	48
apoptosis	0.06	0.28	0.84	50	-10000	0	50
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.062	0.29	-10000	0	-0.92	47	47
ErbB4/ErbB2/epiregulin	-0.054	0.26	-10000	0	-0.77	51	51
ErbB4/ErbB4/betacellulin/betacellulin	-0.081	0.3	-10000	0	-0.86	53	53
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.034	0.28	-10000	0	-0.71	59	59
MDM2	-0.069	0.29	0.28	14	-0.93	45	59
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.045	0.23	-10000	0	-0.78	43	43
STAT5A	-0.042	0.28	0.32	7	-0.87	45	52
ErbB4/EGFR/neuregulin 1 beta	-0.07	0.25	-10000	0	-0.81	45	45
DLG4	0.032	0.012	-10000	0	-10000	0	0
GRB2/SHC	0.038	0.028	-10000	0	-0.3	1	1
E4ICDs/TAB2/NCoR1	-0.048	0.28	-10000	0	-0.87	46	46
STAT5A (dimer)	-0.022	0.28	-10000	0	-0.81	48	48
MAP3K7IP2	0.031	0.03	-10000	0	-0.42	2	2
STAT5B (dimer)	-0.045	0.28	-10000	0	-0.86	47	47
LRIG1	0.005	0.11	-10000	0	-0.42	32	32
EREG	0.025	0.051	-10000	0	-0.42	6	6
BTC	-0.012	0.14	-10000	0	-0.42	50	50
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.071	0.28	-10000	0	-0.91	46	46
ERBB4	-0.081	0.31	-10000	0	-1	45	45
STAT5B	0.03	0.024	-10000	0	-0.42	1	1
YAP1	-0.023	0.15	-10000	0	-0.42	46	46
GRB2	0.033	0.01	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.049	0.26	-10000	0	-0.77	50	50
glial cell differentiation	0.047	0.27	0.85	46	-10000	0	46
WWOX	0.027	0.016	-10000	0	-10000	0	0
cell proliferation	-0.08	0.26	0.33	1	-0.8	49	50

×

Coregulation of Androgen receptor activity

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
NRIP1	-0.01	0.14	-9999	-0.42	51	51
SVIL	0.022	0.078	-9999	-0.42	15	15
ZNF318	0.032	0.007	-9999	-10000	0	0
JMJD2C	0.039	0.01	-9999	-10000	0	0
T-DHT/AR/Ubc9	-0.038	0.13	-9999	-0.25	111	111
CARM1	0.034	0.021	-9999	-0.42	1	1
PRDX1	0.032	0.036	-9999	-0.42	3	3
PELP1	0.032	0.011	-9999	-10000	0	0
CTNNB1	0.025	0.067	-9999	-0.42	11	11
AKT1	0.031	0.036	-9999	-0.42	3	3
PTK2B	0.028	0.016	-9999	-10000	0	0
MED1	-0.001	0	-9999	-10000	0	0
MAK	0.024	0.046	-9999	-0.42	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.036	0.006	-9999	-10000	0	0
GSN	0.022	0.08	-9999	-0.42	16	16
NCOA2	0.025	0.047	-9999	-0.42	5	5
NCOA6	0.036	0.008	-9999	-10000	0	0
DNA-PK	0.054	0.035	-9999	-0.25	2	2
NCOA4	0.03	0.05	-9999	-0.42	6	6
PIAS3	0.036	0.006	-9999	-10000	0	0
cell proliferation	-0.014	0.096	-9999	-0.57	12	12
XRCC5	0.035	0.004	-9999	-10000	0	0
UBE3A	0.036	0.029	-9999	-0.42	2	2
T-DHT/AR/SNURF	-0.052	0.12	-9999	-0.17	213	213
FHL2	-0.12	0.32	-9999	-0.9	69	69
RANBP9	0.036	0.007	-9999	-10000	0	0
JMJD1A	0.009	0.072	-9999	-0.15	88	88
CDK6	0.025	0.054	-9999	-0.42	7	7
TGFB1I1	0.017	0.085	-9999	-0.42	18	18
T-DHT/AR/CyclinD1	-0.074	0.17	-9999	-0.34	133	133
XRCC6	0.033	0.009	-9999	-10000	0	0
T-DHT/AR	-0.065	0.14	-9999	-0.22	213	213
CTDSP1	0.034	0.029	-9999	-0.42	2	2
CTDSP2	0.032	0.029	-9999	-0.42	2	2
BRCA1	0.022	0.07	-9999	-0.42	12	12
TCF4	0.015	0.089	-9999	-0.42	20	20
CDKN2A	0.014	0.075	-9999	-0.42	14	14
SRF	0.016	0.061	-9999	-0.15	47	47
NKX3-1	-0.049	0.1	-9999	-0.24	92	92
KLK3	0.021	0.053	-9999	-10000	0	0
TMF1	0.035	0.007	-9999	-10000	0	0
HNRNPA1	-0.001	0	-9999	-10000	0	0
AOF2	0.036	0.008	-9999	-10000	0	0
APPL1	-0.007	0.023	-9999	-0.3	3	3
T-DHT/AR/Caspase 8	-0.04	0.13	-9999	-0.25	113	113
AR	-0.078	0.18	-9999	-0.39	114	114
UBA3	0	0	-9999	-10000	0	0
PATZ1	-0.001	0	-9999	-10000	0	0
PAWR	0.024	0.073	-9999	-0.42	13	13
PRKDC	0.028	0.031	-9999	-0.42	2	2
PA2G4	0.034	0.005	-9999	-10000	0	0
UBE2I	0.032	0.011	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.032	0.12	-9999	-0.23	108	108
RPS6KA3	0.033	0.041	-9999	-0.42	4	4
T-DHT/AR/ARA70	-0.043	0.13	-9999	-0.26	118	118
LATS2	0.024	0.061	-9999	-0.42	9	9
T-DHT/AR/PRX1	-0.037	0.12	-9999	-0.23	116	116
Cyclin D3/CDK11 p58	0.026	0.005	-9999	-10000	0	0
VAV3	-0.039	0.17	-9999	-0.42	81	81
KLK2	-0.014	0.088	-9999	-0.39	15	15
CASP8	0.035	0.004	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.022	0.12	-9999	-0.23	98	98
TMPRSS2	-0.15	0.35	-9999	-0.88	91	91
CCND1	-0.042	0.16	-9999	-0.42	79	79
PIAS1	0.037	0.007	-9999	-10000	0	0
mol:T-DHT	-0.014	0.03	-9999	-0.065	120	120
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.035	0.036	-9999	-0.42	3	3
T-DHT/AR/CDK6	-0.042	0.13	-9999	-0.25	117	117
CMTM2	0.028	0.024	-9999	-0.42	1	1
SNURF	0	0	-9999	-10000	0	0
ZMIZ1	-0.014	0.03	-9999	-0.065	120	120
CCND3	0.035	0.007	-9999	-10000	0	0
TGIF1	-0.001	0	-9999	-10000	0	0
FKBP4	0.03	0.046	-9999	-0.42	5	5

×

PLK2 and PLK4 events

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
PLK2	-0.007	0.13	-9999	-0.42	43	43
PLK4	0.03	0.05	-9999	-0.42	6	6
regulation of centriole replication	-0.015	0.093	-9999	-0.3	48	48

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.013	0.12	-10000	0	-0.57	3	3
UGCG	-0.09	0.27	-10000	0	-0.72	73	73
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.063	0.19	0.31	1	-0.38	92	93
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.089	0.26	-10000	0	-0.71	74	74
mol:DAG	-0.006	0.027	0.17	11	-10000	0	11
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.08	0.23	0.34	1	-0.47	87	88
FRAP1	-0.1	0.26	0.36	1	-0.54	89	90
FOXO3	-0.05	0.2	0.36	1	-0.51	49	50
AKT1	-0.055	0.22	0.38	1	-0.56	49	50
GAB2	0.028	0.015	-10000	0	-10000	0	0
SMPD1	-0.004	0.13	-10000	0	-0.69	15	15
SGMS1	-0.004	0.034	0.058	1	-0.079	45	46
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	-0.009	0.049	-10000	0	-0.25	18	18
CALM1	0.035	0.007	-10000	0	-10000	0	0
cell proliferation	-0.041	0.18	0.28	3	-0.37	95	98
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	0.033	0.068	-10000	0	-0.3	18	18
RPS6KB1	-0.043	0.16	-10000	0	-0.84	13	13
mol:sphingomyelin	-0.006	0.027	0.17	11	-10000	0	11
natural killer cell activation	-0.002	0.004	-10000	0	-0.011	57	57
JAK3	0.035	0.009	-10000	0	-10000	0	0
PIK3R1	0.017	0.083	-10000	0	-0.42	17	17
JAK1	0.031	0.037	-10000	0	-0.42	3	3
NFKB1	0.035	0.005	-10000	0	-10000	0	0
MYC	-0.027	0.29	0.49	2	-0.95	35	37
MYB	-0.23	0.5	-10000	0	-1.2	106	106
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.022	0.15	-10000	0	-0.4	37	37
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.025	0.16	-10000	0	-0.74	13	13
mol:PI-3-4-5-P3	-0.02	0.15	-10000	0	-0.39	37	37
Rac1/GDP	0.007	0.052	-10000	0	-0.23	18	18
T cell proliferation	-0.018	0.14	0.29	3	-0.37	37	40
SHC1	0.025	0.026	-10000	0	-0.42	1	1
RAC1	0.035	0.006	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.01	0.028	-10000	0	-0.065	103	103
PRKCZ	-0.021	0.15	-10000	0	-0.38	37	37
NF kappa B1 p50/RelA	-0.07	0.24	0.36	1	-0.47	86	87
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.012	0.13	-10000	0	-0.42	30	30
HSP90AA1	0	0	-10000	0	-10000	0	0
RELA	0.035	0.006	-10000	0	-10000	0	0
IL2RA	0.001	0.11	-10000	0	-0.42	31	31
IL2RB	0.011	0.095	-10000	0	-0.42	23	23
TERT	0.032	0.03	-10000	0	-0.42	2	2
E2F1	-0.073	0.2	-10000	0	-0.43	113	113
SOS1	0.032	0.023	-10000	0	-0.43	1	1
RPS6	0.034	0.022	-10000	0	-0.42	1	1
mol:cAMP	0.004	0.013	0.031	100	-10000	0	100
PTPN11	0.032	0.013	-10000	0	-10000	0	0
IL2RG	0.029	0.042	-10000	0	-0.42	4	4
actin cytoskeleton organization	-0.018	0.14	0.29	3	-0.37	37	40
GRB2	0.03	0.013	-10000	0	-10000	0	0
IL2	0.03	0.037	-10000	0	-0.42	3	3
PIK3CA	0.032	0.024	-10000	0	-0.43	1	1
Rac1/GTP	0.032	0.065	-10000	0	-0.22	18	18
LCK	-0.019	0.14	-10000	0	-0.42	54	54
BCL2	-0.18	0.38	-10000	0	-0.84	114	114

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.052	0.052	0.23	20	-0.43	1	21
AES	0.051	0.042	0.21	20	-10000	0	20
FBXW11	0.034	0.021	-10000	0	-0.42	1	1
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
LRP6/FZD1	0.04	0.053	-10000	0	-0.3	11	11
SMAD4	0.028	0.054	-10000	0	-0.42	7	7
DKK2	0.006	0.11	-10000	0	-0.42	31	31
TLE1	0.021	0.12	0.22	21	-0.42	33	54
MACF1	0.034	0.021	-10000	0	-0.42	1	1
CTNNB1	-0.001	0.1	0.27	5	-0.37	11	16
WIF1	0.03	0.014	-10000	0	-10000	0	0
beta catenin/RanBP3	0.073	0.2	0.41	113	-0.36	7	120
KREMEN2	-0.091	0.19	-10000	0	-0.42	129	129
DKK1	-0.028	0.15	-10000	0	-0.42	61	61
beta catenin/beta TrCP1	0.012	0.11	0.28	5	-0.37	9	14
FZD1	0.028	0.054	-10000	0	-0.42	7	7
AXIN2	-0.049	0.39	0.6	51	-1.3	32	83
AXIN1	0.036	0.002	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.044	0.065	-10000	0	-0.59	4	4
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.007	0.17	0.33	5	-0.48	35	40
Axin1/APC/GSK3	0.033	0.049	-10000	0	-0.31	1	1
Axin1/APC/GSK3/beta catenin/Macf1	0.021	0.08	0.31	4	-0.36	5	9
HNF1A	0.017	0.045	0.19	22	-10000	0	22
CTBP1	0.049	0.045	0.23	17	-10000	0	17
MYC	0.032	0.47	0.59	113	-1.3	37	150
RANBP3	0.036	0.007	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.044	0.15	-10000	0	-0.26	153	153
NKD1	0.026	0.037	-10000	0	-0.42	3	3
TCF4	0.033	0.099	0.22	20	-0.4	20	40
TCF3	0.047	0.056	0.22	18	-0.42	3	21
WNT1/LRP6/FZD1/Axin1	0.076	0.057	-10000	0	-0.24	12	12
Ran/GTP	0.028	0.005	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.089	0.26	0.53	100	-0.47	12	112
LEF1	0.037	0.086	0.25	12	-0.41	13	25
DVL1	0.031	0.049	-10000	0	-0.28	3	3
CSNK2A1	0.035	0.008	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.044	0.18	-10000	0	-0.53	37	37
DKK1/LRP6/Kremen 2	-0.062	0.16	-10000	0	-0.28	169	169
LRP6	0.029	0.046	-10000	0	-0.42	5	5
CSNK1A1	0.053	0.047	0.23	20	-10000	0	20
NLK	0.028	0.027	-10000	0	-0.43	1	1
CCND1	-0.15	0.6	0.58	73	-1.4	86	159
WNT1	0.034	0.021	-10000	0	-0.42	1	1
GSK3A	0.035	0.004	-10000	0	-10000	0	0
GSK3B	0.035	0.005	-10000	0	-10000	0	0
FRAT1	0.029	0.054	-10000	0	-0.42	7	7
PPP2R5D	0.029	0.065	0.24	2	-0.31	7	9
APC	-0.014	0.058	0.2	18	-0.22	16	34
WNT1/LRP6/FZD1	0.022	0.049	-10000	0	-0.23	8	8
CREBBP	0.048	0.044	0.22	15	-10000	0	15

×

E-cadherin signaling in keratinocytes

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.013	0.089	0.22	1	-0.29	17	18
adherens junction organization	-0.045	0.13	-10000	0	-0.38	34	34
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.013	0.11	0.27	2	-0.31	16	18
FMN1	-0.034	0.12	-10000	0	-0.26	84	84
mol:IP3	-0.016	0.076	-10000	0	-0.25	17	17
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.033	0.13	-10000	0	-0.27	84	84
CTNNB1	0.026	0.067	-10000	0	-0.42	11	11
AKT1	-0.017	0.094	0.19	1	-0.29	19	20
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.061	0.19	-10000	0	-0.43	74	74
CTNND1	0.034	0.022	-10000	0	-0.43	1	1
mol:PI-4-5-P2	-0.031	0.12	0.22	1	-0.26	75	76
VASP	-0.038	0.12	-10000	0	-0.27	78	78
ZYX	-0.037	0.12	-10000	0	-0.27	81	81
JUB	-0.047	0.13	-10000	0	-0.28	83	83
EGFR(dimer)	-0.04	0.14	-10000	0	-0.33	51	51
E-cadherin/beta catenin-gamma catenin	0.015	0.1	-10000	0	-0.24	58	58
mol:PI-3-4-5-P3	0	0.11	-10000	0	-0.3	17	17
PIK3CA	0.034	0.022	-10000	0	-0.42	1	1
PI3K	0	0.11	-10000	0	-0.3	17	17
FYN	-0.018	0.091	0.22	1	-0.3	20	21
mol:Ca2+	-0.015	0.074	-10000	0	-0.25	17	17
JUP	0.03	0.042	-10000	0	-0.42	4	4
PIK3R1	0.019	0.083	-10000	0	-0.42	17	17
mol:DAG	-0.016	0.076	-10000	0	-0.25	17	17
CDH1	-0.012	0.13	-10000	0	-0.42	45	45
RhoA/GDP	-0.016	0.11	0.23	1	-0.28	31	32
establishment of polarity of embryonic epithelium	-0.036	0.12	0.22	1	-0.27	78	79
SRC	0.032	0.03	-10000	0	-0.42	2	2
RAC1	0.035	0.006	-10000	0	-10000	0	0
RHOA	0.026	0.061	-10000	0	-0.42	9	9
EGFR	-0.013	0.13	-10000	0	-0.42	47	47
CASR	-0.014	0.077	0.22	1	-0.27	11	12
RhoA/GTP	-0.002	0.089	0.21	1	-0.26	15	16
AKT2	-0.016	0.093	0.19	1	-0.29	17	18
actin cable formation	-0.036	0.12	0.2	5	-0.34	32	37
apoptosis	0.009	0.1	0.29	20	-0.26	4	24
CTNNA1	0.036	0.007	-10000	0	-10000	0	0
mol:GDP	-0.029	0.099	0.22	1	-0.28	33	34
PIP5K1A	-0.033	0.12	-10000	0	-0.26	75	75
PLCG1	-0.016	0.077	-10000	0	-0.26	17	17
Rac1/GTP	-0.029	0.14	-10000	0	-0.32	48	48
homophilic cell adhesion	0	0.004	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.028	0.057	-10000	0	-0.42	8	8
Jak2/Leptin Receptor	-0.034	0.14	-10000	0	-0.36	45	45
PTP1B/AKT1	-0.043	0.13	0.26	3	-0.3	67	70
FYN	0.027	0.05	-10000	0	-0.42	6	6
p210 bcr-abl/PTP1B	-0.06	0.14	0.28	3	-0.33	69	72
EGFR	-0.023	0.13	-10000	0	-0.43	47	47
EGF/EGFR	-0.089	0.18	0.29	2	-0.31	157	159
CSF1	0.034	0.022	-10000	0	-0.42	1	1
AKT1	0.032	0.036	-10000	0	-0.43	3	3
INSR	0.034	0.03	-10000	0	-0.43	2	2
PTP1B/N-cadherin	-0.054	0.15	0.29	2	-0.35	64	66
Insulin Receptor/Insulin	-0.008	0.13	0.31	2	-0.34	35	37
HCK	0.017	0.087	-10000	0	-0.42	19	19
CRK	0.031	0.023	-10000	0	-0.42	1	1
TYK2	-0.058	0.13	0.26	6	-0.33	60	66
EGF	-0.074	0.19	-10000	0	-0.43	110	110
YES1	0.029	0.05	-10000	0	-0.42	6	6
CAV1	-0.069	0.15	0.27	3	-0.33	81	84
TXN	0.033	0.007	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.054	0.16	0.3	2	-0.33	80	82
cell migration	0.06	0.14	0.33	69	-0.28	3	72
STAT3	0.028	0.031	-10000	0	-0.42	2	2
PRLR	0.001	0.12	-10000	0	-0.41	42	42
ITGA2B	0.033	0.009	-10000	0	-10000	0	0
CSF1R	0.035	0.006	-10000	0	-10000	0	0
Prolactin Receptor/Prolactin	0.027	0.098	-10000	0	-0.3	41	41
FGR	0.034	0.008	-10000	0	-10000	0	0
PTP1B/p130 Cas	-0.043	0.14	0.29	1	-0.32	64	65
Crk/p130 Cas	-0.036	0.14	0.3	1	-0.32	58	59
DOK1	-0.053	0.14	0.26	3	-0.36	55	58
JAK2	-0.043	0.14	-10000	0	-0.39	42	42
Jak2/Leptin Receptor/Leptin	-0.044	0.14	0.25	1	-0.38	38	39
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
PTPN1	-0.06	0.14	0.28	3	-0.33	70	73
LYN	0.03	0.014	-10000	0	-10000	0	0
CDH2	0.011	0.093	-10000	0	-0.42	22	22
SRC	-0.004	0.12	-10000	0	-0.61	15	15
ITGB3	0.028	0.046	-10000	0	-0.43	5	5
CAT1/PTP1B	-0.082	0.2	0.31	3	-0.47	72	75
CAPN1	0.024	0.065	-10000	0	-0.43	10	10
CSK	0.033	0.022	-10000	0	-0.42	1	1
PI3K	-0.003	0.14	0.28	2	-0.34	39	41
mol:H2O2	-0.001	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.034	0.13	-10000	0	-0.37	33	33
negative regulation of transcription	-0.042	0.14	-10000	0	-0.38	42	42
FCGR2A	0.017	0.07	-10000	0	-0.42	12	12
FER	0.032	0.022	-10000	0	-0.43	1	1
alphaIIb/beta3 Integrin	0.044	0.035	-10000	0	-0.31	4	4
BLK	0.021	0.038	-10000	0	-0.42	3	3
Insulin Receptor/Insulin/Shc	0.052	0.04	-10000	0	-0.26	3	3
RHOA	0.025	0.062	-10000	0	-0.43	9	9
LEPR	0.027	0.054	-10000	0	-0.42	7	7
BCAR1	0.029	0.014	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.033	0.01	-10000	0	-10000	0	0
mol:NADPH	-0.002	0.004	-10000	0	-10000	0	0
TRPV6	-0.068	0.21	0.26	1	-0.49	74	75
PRL	0.035	0.026	-10000	0	-0.26	3	3
SOCS3	0.008	0.18	-10000	0	-1.3	9	9
SPRY2	0.005	0.11	-10000	0	-0.43	28	28
Insulin Receptor/Insulin/IRS1	0.031	0.11	-10000	0	-0.27	55	55
CSF1/CSF1R	-0.033	0.14	0.3	2	-0.32	58	60
Ras protein signal transduction	0.055	0.17	0.62	40	-10000	0	40
IRS1	-0.014	0.14	-10000	0	-0.42	54	54
INS	0.034	0.022	-10000	0	-0.43	1	1
LEP	-0.002	0.12	-10000	0	-0.42	36	36
STAT5B	-0.05	0.13	0.25	2	-0.33	58	60
STAT5A	-0.052	0.14	0.23	3	-0.33	62	65
GRB2	0.033	0.01	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.049	0.15	0.29	2	-0.34	65	67
CSN2	0.021	0.1	-10000	0	-1.4	2	2
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
LAT	-0.009	0.12	-10000	0	-0.54	19	19
YBX1	0.037	0.044	-10000	0	-0.38	5	5
LCK	-0.018	0.14	-10000	0	-0.42	54	54
SHC1	0.027	0.025	-10000	0	-0.42	1	1
NOX4	-0.022	0.14	-10000	0	-0.43	57	57

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.024	0.025	-10000	0	-0.3	3	3
alphaV beta3 Integrin	0.029	0.1	-10000	0	-0.27	52	52
PTK2	0.008	0.12	0.36	4	-0.41	19	23
IGF1R	-0.043	0.17	-10000	0	-0.42	84	84
PI4KB	0	0	-10000	0	-10000	0	0
MFGE8	0.016	0.085	-10000	0	-0.42	18	18
SRC	0.032	0.03	-10000	0	-0.42	2	2
CDKN1B	-0.009	0.12	-10000	0	-0.46	29	29
VEGFA	0	0	-10000	0	-10000	0	0
ILK	0.014	0.06	-10000	0	-0.5	4	4
ROCK1	0.035	0.005	-10000	0	-10000	0	0
AKT1	0.001	0.073	0.21	4	-0.41	8	12
PTK2B	0.005	0.06	0.21	9	-0.24	21	30
alphaV/beta3 Integrin/JAM-A	0.058	0.1	-10000	0	-0.23	43	43
CBL	0.031	0.012	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.049	0.076	-10000	0	-0.27	25	25
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.04	0.2	-10000	0	-0.32	153	153
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.007	0.068	-10000	0	-0.23	27	27
alphaV/beta3 Integrin/Syndecan-1	0.029	0.11	-10000	0	-0.27	56	56
PI4KA	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.08	0.22	-10000	0	-0.33	188	188
PI4 Kinase	0	0	-10000	0	-10000	0	0
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
alphaV/beta3 Integrin/Osteopontin	-0.022	0.15	-10000	0	-0.28	127	127
RPS6KB1	-0.12	0.17	0.43	2	-0.45	78	80
TLN1	0.034	0.021	-10000	0	-0.42	1	1
MAPK3	-0.047	0.2	-10000	0	-0.54	56	56
GPR124	0.017	0.073	-10000	0	-0.42	13	13
MAPK1	-0.05	0.2	-10000	0	-0.55	59	59
PXN	0.036	0.004	-10000	0	-10000	0	0
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
alphaV/beta3 Integrin/Tumstatin	0.052	0.074	-10000	0	-0.28	22	22
cell adhesion	0.023	0.1	-10000	0	-0.27	49	49
ANGPTL3	0.03	0.046	-10000	0	-0.42	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	0.043	0.03	-10000	0	-0.25	4	4
IGF-1R heterotetramer	-0.043	0.17	-10000	0	-0.42	84	84
Rac1/GDP	0.026	0.004	-10000	0	-10000	0	0
TGFBR2	0.032	0.036	-10000	0	-0.42	3	3
ITGB3	0.029	0.046	-10000	0	-0.42	5	5
IGF1	-0.041	0.17	-10000	0	-0.42	80	80
RAC1	0.035	0.006	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.034	0.087	-10000	0	-0.3	27	27
apoptosis	0.021	0.08	-10000	0	-0.42	16	16
CD47	0.018	0.085	-10000	0	-0.42	18	18
alphaV/beta3 Integrin/CD47	0.041	0.09	-10000	0	-0.26	38	38
VCL	0.035	0.021	-10000	0	-0.42	1	1
alphaV/beta3 Integrin/Del1	-0.01	0.15	-10000	0	-0.29	104	104
CSF1	0.034	0.022	-10000	0	-0.42	1	1
PIK3C2A	0.009	0.085	-10000	0	-0.55	9	9
PI4 Kinase/Pyk2	0.003	0.076	-10000	0	-0.21	51	51
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.05	0.069	-10000	0	-0.26	21	21
FAK1/Vinculin	0.027	0.11	0.31	6	-0.33	19	25
alphaV beta3/Integrin/ppsTEM5	0.034	0.087	-10000	0	-0.3	27	27
RHOA	0.026	0.061	-10000	0	-0.42	9	9
VTN	0.035	0.007	-10000	0	-10000	0	0
BCAR1	0.029	0.014	-10000	0	-10000	0	0
FGF2	-0.001	0.11	-10000	0	-0.42	34	34
F11R	-0.005	0.072	-10000	0	-0.3	28	28
alphaV/beta3 Integrin/Lactadherin	0.043	0.093	-10000	0	-0.31	28	28
alphaV/beta3 Integrin/TGFBR2	0.051	0.072	-10000	0	-0.27	22	22
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.058	0.067	-10000	0	-0.24	16	16
HSP90AA1	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.05	0.065	-10000	0	-0.24	21	21
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.009	0.13	-10000	0	-0.42	48	48
alphaV/beta3 Integrin/Pyk2	0.034	0.066	0.2	3	-0.24	21	24
SDC1	-0.002	0.12	-10000	0	-0.42	41	41
VAV3	-0.051	0.089	0.18	3	-0.24	88	91
PTPN11	0.036	0.004	-10000	0	-10000	0	0
IRS1	-0.014	0.14	-10000	0	-0.42	54	54
FAK1/Paxillin	0.026	0.12	0.33	5	-0.33	19	24
cell migration	0.02	0.11	0.24	14	-0.3	19	33
ITGAV	0.021	0.08	-10000	0	-0.42	16	16
PI3K	0.058	0.11	-10000	0	-0.23	49	49
SPP1	-0.075	0.19	-10000	0	-0.42	117	117
KDR	0.033	0.035	-10000	0	-0.42	3	3
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.021	0.08	-10000	0	-0.42	16	16
COL4A3	0.032	0.036	-10000	0	-0.42	3	3
angiogenesis	-0.037	0.21	-10000	0	-0.57	52	52
Rac1/GTP	-0.013	0.098	-10000	0	-0.22	87	87
EDIL3	-0.056	0.18	-10000	0	-0.42	97	97
cell proliferation	0.051	0.072	-10000	0	-0.27	22	22

×

E-cadherin signaling in the nascent adherens junction

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.07	0.16	-10000	0	-0.41	64	64
KLHL20	-0.025	0.09	0.25	1	-0.26	17	18
CYFIP2	-0.006	0.13	-10000	0	-0.42	44	44
Rac1/GDP	-0.034	0.12	0.26	5	-0.27	60	65
ENAH	-0.064	0.16	-10000	0	-0.42	62	62
AP1M1	0.034	0.021	-10000	0	-0.42	1	1
RAP1B	0.032	0.03	-10000	0	-0.42	2	2
RAP1A	0.03	0.05	-10000	0	-0.42	6	6
CTNNB1	0.024	0.067	-10000	0	-0.42	11	11
CDC42/GTP	-0.013	0.084	-10000	0	-0.23	13	13
ABI1/Sra1/Nap1	-0.046	0.054	-10000	0	-0.16	36	36
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.03	0.1	-10000	0	-0.24	58	58
RAPGEF1	-0.071	0.16	-10000	0	-0.37	76	76
CTNND1	0.033	0.022	-10000	0	-0.42	1	1
regulation of calcium-dependent cell-cell adhesion	-0.073	0.18	-10000	0	-0.42	81	81
CRK	-0.068	0.16	-10000	0	-0.39	79	79
E-cadherin/gamma catenin/alpha catenin	0.019	0.098	-10000	0	-0.26	48	48
alphaE/beta7 Integrin	0.044	0.039	-10000	0	-0.3	5	5
IQGAP1	0.034	0.008	-10000	0	-10000	0	0
NCKAP1	0.034	0.021	-10000	0	-0.42	1	1
Rap1/GTP/I-afadin	0.047	0.063	-10000	0	-0.23	21	21
DLG1	-0.082	0.18	-10000	0	-0.4	85	85
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.031	0.057	-10000	0	-0.17	21	21
MLLT4	0.02	0.075	-10000	0	-0.42	14	14
ARF6/GTP/NME1/Tiam1	0.056	0.045	-10000	0	-0.24	9	9
PI3K	-0.036	0.074	-10000	0	-0.22	19	19
ARF6	0.033	0.029	-10000	0	-0.42	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.004	0.1	-10000	0	-0.31	48	48
TIAM1	0.028	0.057	-10000	0	-0.42	8	8
E-cadherin(dimer)/Ca2+	0.03	0.096	-10000	0	-0.22	56	56
AKT1	-0.025	0.054	0.18	4	-0.17	6	10
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
CDH1	-0.012	0.13	-10000	0	-0.42	45	45
RhoA/GDP	-0.034	0.12	0.26	5	-0.27	61	66
actin cytoskeleton organization	-0.017	0.068	0.17	2	-0.19	16	18
CDC42/GDP	-0.032	0.12	0.26	5	-0.26	60	65
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.01	0.077	-10000	0	-0.22	55	55
ITGB7	0.036	0.004	-10000	0	-10000	0	0
RAC1	0.035	0.006	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.032	0.1	-10000	0	-0.24	56	56
E-cadherin/Ca2+/beta catenin/alpha catenin	0.018	0.087	-10000	0	-0.22	55	55
mol:GDP	-0.053	0.12	0.26	5	-0.3	62	67
CDC42/GTP/IQGAP1	0.045	0.014	-10000	0	-10000	0	0
JUP	0.028	0.042	-10000	0	-0.42	4	4
p120 catenin/RhoA/GDP	-0.03	0.13	0.27	4	-0.28	60	64
RAC1/GTP/IQGAP1	0.045	0.012	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.048	0.033	-10000	0	-0.3	4	4
RHOA	0.026	0.061	-10000	0	-0.42	9	9
CDC42	0.034	0.008	-10000	0	-10000	0	0
CTNNA1	0.035	0.006	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.031	0.077	0.14	2	-0.19	80	82
NME1	0.033	0.01	-10000	0	-10000	0	0
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.079	0.18	-10000	0	-0.41	81	81
regulation of cell-cell adhesion	-0.018	0.069	-10000	0	-0.18	54	54
WASF2	-0.016	0.042	0.11	3	-0.11	9	12
Rap1/GTP	-0.014	0.093	0.25	2	-0.25	13	15
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.036	0.1	-10000	0	-0.23	52	52
CCND1	-0.038	0.095	0.16	2	-0.23	80	82
VAV2	-0.066	0.19	-10000	0	-0.56	15	15
RAP1/GDP	-0.018	0.1	0.27	2	-0.26	17	19
adherens junction assembly	-0.077	0.17	-10000	0	-0.4	82	82
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.034	0.008	-10000	0	-10000	0	0
PIP5K1C	0.032	0.036	-10000	0	-0.42	3	3
regulation of heterotypic cell-cell adhesion	0.028	0.1	-10000	0	-0.22	61	61
E-cadherin/beta catenin	-0.025	0.1	-10000	0	-0.29	63	63
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.08	0.17	-10000	0	-0.41	84	84
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
Rac1/GTP	-0.076	0.13	-10000	0	-0.39	31	31
E-cadherin/beta catenin/alpha catenin	0.02	0.1	-10000	0	-0.26	55	55
ITGAE	0.028	0.046	-10000	0	-0.42	5	5
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.075	0.19	-10000	0	-0.43	81	81

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.006	0.1	-10000	0	-0.3	50	50
EPHB2	0.032	0.03	-10000	0	-0.42	2	2
Syndecan-2/TACI	0.011	0.064	-10000	0	-0.25	27	27
LAMA1	0.034	0.009	-10000	0	-10000	0	0
Syndecan-2/alpha2 ITGB1	0.02	0.13	-10000	0	-0.25	84	84
HRAS	0.032	0.036	-10000	0	-0.42	3	3
Syndecan-2/CASK	-0.005	0.057	-10000	0	-0.24	27	27
ITGA5	0.033	0.035	-10000	0	-0.42	3	3
BAX	-0.008	0.051	-10000	0	-10000	0	0
EPB41	0.034	0.021	-10000	0	-0.42	1	1
positive regulation of cell-cell adhesion	0.008	0.065	-10000	0	-0.23	33	33
LAMA3	-0.019	0.14	-10000	0	-0.42	57	57
EZR	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.014	0.091	-10000	0	-0.42	21	21
Syndecan-2/MMP2	0	0.088	-10000	0	-0.29	38	38
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.016	0.1	-10000	0	-0.3	46	46
dendrite morphogenesis	0.012	0.065	-10000	0	-0.25	28	28
Syndecan-2/GM-CSF	0.011	0.066	-10000	0	-0.25	29	29
determination of left/right symmetry	-0.005	0.068	-10000	0	-0.29	27	27
Syndecan-2/PKC delta	0.012	0.066	-10000	0	-0.25	29	29
GNB2L1	0.033	0.035	-10000	0	-0.42	3	3
MAPK3	0.032	0.09	0.2	82	-0.22	27	109
MAPK1	0.036	0.094	0.2	94	-0.22	28	122
Syndecan-2/RACK1	0.025	0.067	-10000	0	-0.22	30	30
NF1	0.032	0.03	-10000	0	-0.42	2	2
FGFR/FGF/Syndecan-2	-0.005	0.068	-10000	0	-0.29	27	27
ITGA2	-0.009	0.13	-10000	0	-0.42	47	47
MAPK8	-0.005	0.058	-10000	0	-0.24	28	28
Syndecan-2/alpha2/beta1 Integrin	0.044	0.11	-10000	0	-0.24	48	48
Syndecan-2/Kininogen	0.012	0.064	-10000	0	-0.25	27	27
ITGB1	0.033	0.03	-10000	0	-0.42	2	2
SRC	0.037	0.093	0.19	98	-0.22	28	126
Syndecan-2/CASK/Protein 4.1	0.012	0.059	-10000	0	-0.22	28	28
extracellular matrix organization	0.013	0.064	-10000	0	-0.25	27	27
actin cytoskeleton reorganization	-0.006	0.1	-10000	0	-0.3	50	50
Syndecan-2/Caveolin-2/Ras	0.017	0.09	-10000	0	-0.27	39	39
Syndecan-2/Laminin alpha3	-0.012	0.1	-10000	0	-0.26	67	67
Syndecan-2/RasGAP	0.033	0.075	-10000	0	-0.21	35	35
alpha5/beta1 Integrin	0.047	0.037	-10000	0	-0.3	5	5
PRKCD	0.032	0.03	-10000	0	-0.42	2	2
Syndecan-2 dimer	0.012	0.065	-10000	0	-0.25	28	28
GO:0007205	0.003	0.001	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.018	0.067	0.19	1	-0.21	33	34
RHOA	0.026	0.061	-10000	0	-0.42	9	9
SDCBP	0.022	0.061	-10000	0	-0.42	9	9
TNFRSF13B	0.032	0.012	-10000	0	-10000	0	0
RASA1	0.028	0.054	-10000	0	-0.42	7	7
alpha2/beta1 Integrin	0.016	0.1	-10000	0	-0.3	46	46
Syndecan-2/Synbindin	0.011	0.063	-10000	0	-0.25	27	27
TGFB1	0.035	0.021	-10000	0	-0.42	1	1
CASP3	0.036	0.094	0.2	93	-0.22	28	121
FN1	-0.009	0.13	-10000	0	-0.42	48	48
Syndecan-2/IL8	-0.007	0.094	-10000	0	-0.27	52	52
SDC2	-0.005	0.068	-10000	0	-0.29	27	27
KNG1	0.034	0.008	-10000	0	-10000	0	0
Syndecan-2/Neurofibromin	0.011	0.066	-10000	0	-0.25	29	29
TRAPPC4	0.031	0.012	-10000	0	-10000	0	0
CSF2	0.03	0.036	-10000	0	-0.42	3	3
Syndecan-2/TGFB1	0.013	0.064	-10000	0	-0.25	27	27
Syndecan-2/Syntenin/PI-4-5-P2	0.008	0.065	-10000	0	-0.23	33	33
Syndecan-2/Ezrin	0.009	0.062	-10000	0	-0.22	32	32
PRKACA	0.036	0.095	0.2	95	-0.23	29	124
angiogenesis	-0.007	0.094	-10000	0	-0.27	52	52
MMP2	0.006	0.099	-10000	0	-0.42	25	25
IL8	-0.005	0.12	-10000	0	-0.42	37	37
calcineurin-NFAT signaling pathway	0.011	0.063	-10000	0	-0.25	27	27

×

Cellular roles of Anthrax toxin

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.005	0.11	-10000	0	-0.42	33	33
ANTXR2	0.022	0.075	-10000	0	-0.42	14	14
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.006	0.017	-10000	0	-0.062	41	41
monocyte activation	-0.015	0.12	-10000	0	-0.37	53	53
MAP2K2	0.003	0.1	-10000	0	-0.62	13	13
MAP2K1	-0.009	0.015	-10000	0	-0.087	5	5
MAP2K7	-0.009	0.018	-10000	0	-0.11	6	6
MAP2K6	-0.013	0.042	0.13	4	-0.23	15	19
CYAA	-0.026	0.065	-10000	0	-0.24	41	41
MAP2K4	-0.008	0.018	-10000	0	-0.12	5	5
IL1B	-0.027	0.069	0.14	1	-0.21	53	54
Channel	0.02	0.084	-10000	0	-0.25	41	41
NLRP1	-0.006	0.016	-10000	0	-0.058	41	41
CALM1	0.035	0.007	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.001	0.074	-10000	0	-0.43	13	13
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.006	0.017	0.062	41	-10000	0	41
MAPK3	-0.008	0.023	0.14	5	-0.11	6	11
MAPK1	-0.009	0.018	-10000	0	-0.11	6	6
PGR	-0.075	0.1	-10000	0	-0.22	170	170
PA/Cellular Receptors	0.02	0.092	-10000	0	-0.28	41	41
apoptosis	-0.006	0.017	-10000	0	-0.062	41	41
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.02	0.08	-10000	0	-0.24	41	41
macrophage activation	0.002	0.053	0.17	39	-0.21	2	41
TNF	0.026	0.061	-10000	0	-0.42	9	9
VCAM1	-0.016	0.12	-10000	0	-0.37	53	53
platelet activation	-0.001	0.074	-10000	0	-0.43	13	13
MAPKKK cascade	0.002	0.032	0.13	5	-0.088	14	19
IL18	-0.021	0.063	-10000	0	-0.24	34	34
negative regulation of macrophage activation	-0.006	0.017	-10000	0	-0.062	41	41
LEF	-0.006	0.017	-10000	0	-0.063	41	41
CASP1	-0.008	0.031	-10000	0	-0.083	63	63
mol:cAMP	-0.001	0.075	-10000	0	-0.44	13	13
necrosis	-0.006	0.017	-10000	0	-0.062	41	41
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.02	0.079	-10000	0	-0.24	41	41
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.018	0.11	-10000	0	-0.31	42	42
alphaM/beta2 Integrin/GPIbA	0.033	0.084	-10000	0	-0.3	22	22
alphaM/beta2 Integrin/proMMP-9	0.007	0.12	-10000	0	-0.29	62	62
PLAUR	0.009	0.11	-10000	0	-0.42	29	29
HMGB1	0.025	0.031	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.036	0.087	-10000	0	-0.3	23	23
AGER	0.025	0.038	-10000	0	-0.42	1	1
RAP1A	0.03	0.05	-10000	0	-0.42	6	6
SELPLG	0.024	0.07	-10000	0	-0.42	12	12
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.041	0.12	-10000	0	-0.24	63	63
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	-0.014	0.14	-10000	0	-0.42	52	52
CYR61	-0.003	0.12	-10000	0	-0.42	39	39
TLN1	0.034	0.021	-10000	0	-0.42	1	1
Rap1/GTP	0.01	0.13	-10000	0	-0.34	39	39
RHOA	0.026	0.061	-10000	0	-0.42	9	9
P-selectin oligomer	-0.04	0.16	-10000	0	-0.42	73	73
MYH2	-0.017	0.14	0.23	1	-0.42	34	35
MST1R	-0.005	0.13	-10000	0	-0.42	43	43
leukocyte activation during inflammatory response	0.04	0.079	-10000	0	-0.25	22	22
APOB	0.036	0.004	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.006	0.099	-10000	0	-0.42	25	25
JAM3	0.015	0.085	-10000	0	-0.42	18	18
GP1BA	0.03	0.014	-10000	0	-10000	0	0
alphaM/beta2 Integrin/CTGF	0.017	0.12	-10000	0	-0.32	44	44
alphaM/beta2 Integrin	-0.009	0.13	-10000	0	-0.38	38	38
JAM3 homodimer	0.015	0.085	-10000	0	-0.42	18	18
ICAM2	0.027	0.047	-10000	0	-0.42	5	5
ICAM1	0.016	0.089	-10000	0	-0.42	20	20
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.009	0.13	-10000	0	-0.37	38	38
cell adhesion	0.033	0.084	-10000	0	-0.29	22	22
NFKB1	0	0.15	0.38	1	-0.37	52	53
THY1	0.017	0.08	-10000	0	-0.42	16	16
RhoA/GDP	0.02	0.043	-10000	0	-0.3	9	9
Lipoprotein(a)	0.044	0.014	-10000	0	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	0.017	0.11	-10000	0	-0.26	59	59
IL6	-0.05	0.23	0.36	2	-0.61	65	67
ITGB2	0.005	0.098	-10000	0	-0.43	22	22
elevation of cytosolic calcium ion concentration	0.014	0.15	-10000	0	-0.36	60	60
alphaM/beta2 Integrin/JAM2/JAM3	0.024	0.13	-10000	0	-0.31	49	49
JAM2	0.011	0.099	-10000	0	-0.42	25	25
alphaM/beta2 Integrin/ICAM1	0.038	0.13	-10000	0	-0.28	64	64
alphaM/beta2 Integrin/uPA/Plg	0.025	0.12	-10000	0	-0.29	57	57
RhoA/GTP	-0.029	0.14	-10000	0	-0.44	37	37
positive regulation of phagocytosis	0	0.14	-10000	0	-0.42	35	35
Ron/MSP	0.02	0.099	-10000	0	-0.3	43	43
alphaM/beta2 Integrin/uPAR/uPA	0.016	0.15	-10000	0	-0.36	60	60
alphaM/beta2 Integrin/uPAR	0.023	0.12	-10000	0	-0.33	39	39
PLAU	-0.012	0.14	-10000	0	-0.42	50	50
PLAT	-0.02	0.13	-10000	0	-0.42	49	49
actin filament polymerization	-0.015	0.14	0.24	3	-0.4	33	36
MST1	0.034	0.008	-10000	0	-10000	0	0
alphaM/beta2 Integrin/lipoprotein(a)	0.046	0.082	-10000	0	-0.26	22	22
TNF	-0.016	0.16	0.35	2	-0.42	45	47
RAP1B	0.032	0.03	-10000	0	-0.42	2	2
alphaM/beta2 Integrin/uPA	0.012	0.13	-10000	0	-0.32	55	55
fibrinolysis	0.023	0.12	-10000	0	-0.28	57	57
HCK	0.017	0.087	-10000	0	-0.42	19	19
dendritic cell antigen processing and presentation	-0.009	0.13	-10000	0	-0.37	38	38
VTN	0.035	0.007	-10000	0	-10000	0	0
alphaM/beta2 Integrin/CYR61	0.018	0.12	-10000	0	-0.3	48	48
LPA	0.033	0.01	-10000	0	-10000	0	0
LRP1	0.035	0.021	-10000	0	-0.42	1	1
cell migration	-0.012	0.13	-10000	0	-0.28	75	75
FN1	-0.009	0.13	-10000	0	-0.42	48	48
alphaM/beta2 Integrin/Thy1	0.024	0.1	-10000	0	-0.29	36	36
MPO	0.031	0.012	-10000	0	-10000	0	0
KNG1	0.034	0.008	-10000	0	-10000	0	0
RAP1/GDP	0.041	0.037	-10000	0	-0.25	7	7
ROCK1	-0.019	0.14	0.21	2	-0.42	36	38
ELA2	0.034	0.008	-10000	0	-10000	0	0
PLG	0.031	0.03	-10000	0	-0.42	2	2
CTGF	0.003	0.11	-10000	0	-0.42	32	32
alphaM/beta2 Integrin/Hck	0.029	0.11	-10000	0	-0.37	27	27
ITGAM	0.021	0.053	-10000	0	-0.43	5	5
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.002	0.14	-10000	0	-0.29	76	76
HP	0.027	0.037	-10000	0	-0.42	3	3
leukocyte adhesion	0	0.15	-10000	0	-0.39	43	43
SELP	-0.04	0.16	-10000	0	-0.42	73	73

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.036	0.029	-10000	0	-0.41	1	1
HSPA8	0.018	0.073	-10000	0	-0.42	13	13
SMAD3/SMAD4/ER alpha	-0.033	0.17	0.24	3	-0.29	136	139
AKT1	0.029	0.043	-10000	0	-0.34	4	4
GSC	-0.19	0.48	-10000	0	-1.3	74	74
NKX2-5	0.028	0.022	-10000	0	-10000	0	0
muscle cell differentiation	0.011	0.17	0.37	63	-10000	0	63
SMAD2-3/SMAD4/SP1	0.024	0.18	-10000	0	-0.35	60	60
SMAD4	-0.004	0.096	-10000	0	-0.22	53	53
CBFB	0.029	0.014	-10000	0	-10000	0	0
SAP18	0.033	0.01	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.061	0.047	-10000	0	-0.22	3	3
SMAD3/SMAD4/VDR	0.059	0.12	-10000	0	-0.26	30	30
MYC	-0.002	0.1	-10000	0	-0.42	29	29
CDKN2B	-0.1	0.32	-10000	0	-1.1	36	36
AP1	-0.031	0.18	-10000	0	-0.38	88	88
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.007	0.099	-10000	0	-0.35	19	19
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.007	0.091	-10000	0	-0.27	45	45
SP3	0.028	0.03	-10000	0	-10000	0	0
CREB1	0.034	0.021	-10000	0	-0.42	1	1
FOXH1	0.013	0.059	-10000	0	-0.12	67	67
SMAD3/SMAD4/GR	0.026	0.12	-10000	0	-0.28	43	43
GATA3	-0.043	0.17	-10000	0	-0.42	90	90
SKI/SIN3/HDAC complex/NCoR1	0.014	0.072	-10000	0	-0.32	11	11
MEF2C/TIF2	-0.014	0.13	0.33	1	-0.35	42	43
endothelial cell migration	0.002	0.24	1	21	-10000	0	21
MAX	0.034	0.011	-10000	0	-10000	0	0
RBBP7	0.033	0.029	-10000	0	-0.42	2	2
RBBP4	0.034	0.021	-10000	0	-0.42	1	1
RUNX2	0.031	0.041	-10000	0	-0.42	4	4
RUNX3	-0.01	0.13	-10000	0	-0.42	46	46
RUNX1	0.008	0.11	-10000	0	-0.42	29	29
CTBP1	0.034	0.008	-10000	0	-10000	0	0
NR3C1	0.021	0.078	-10000	0	-0.42	15	15
VDR	0.02	0.083	-10000	0	-0.42	17	17
CDKN1A	-0.039	0.23	-10000	0	-1.2	16	16
KAT2B	0.001	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.016	0.14	-10000	0	-0.28	87	87
DCP1A	0.033	0.022	-10000	0	-0.42	1	1
SKI	0.036	0.002	-10000	0	-10000	0	0
SERPINE1	-0.003	0.24	-10000	0	-1.1	21	21
SMAD3/SMAD4/ATF2	0.034	0.11	-10000	0	-0.26	34	34
SMAD3/SMAD4/ATF3	0.015	0.12	-10000	0	-0.3	42	42
SAP30	0.03	0.046	-10000	0	-0.42	5	5
Cbp/p300/PIAS3	0.066	0.049	0.22	3	-10000	0	3
JUN	-0.043	0.18	-10000	0	-0.43	68	68
SMAD3/SMAD4/IRF7	0.033	0.12	-10000	0	-0.27	42	42
TFE3	0.033	0.034	-10000	0	-0.15	5	5
COL1A2	-0.072	0.32	-10000	0	-0.87	68	68
mesenchymal cell differentiation	-0.03	0.11	0.28	32	-10000	0	32
DLX1	0.032	0.011	-10000	0	-10000	0	0
TCF3	0.031	0.036	-10000	0	-0.42	3	3
FOS	-0.039	0.16	-10000	0	-0.45	66	66
SMAD3/SMAD4/Max	0.032	0.11	-10000	0	-0.26	31	31
Cbp/p300/SNIP1	0.059	0.043	-10000	0	-0.26	3	3
ZBTB17	0.034	0.013	-10000	0	-10000	0	0
LAMC1	-0.006	0.1	-10000	0	-0.39	25	25
TGIF2/HDAC complex/SMAD3/SMAD4	0.027	0.11	-10000	0	-0.26	37	37
IRF7	0.029	0.056	-10000	0	-0.3	12	12
ESR1	-0.082	0.19	-10000	0	-0.41	130	130
HNF4A	0.032	0.03	-10000	0	-0.42	2	2
MEF2C	-0.029	0.14	0.34	3	-0.34	57	60
SMAD2-3/SMAD4	0.018	0.13	-10000	0	-0.27	47	47
Cbp/p300/Src-1	0.061	0.047	-10000	0	-0.23	4	4
IGHV3OR16-13	-0.004	0.065	-10000	0	-0.44	8	8
TGIF2/HDAC complex	0.027	0.054	-10000	0	-0.42	7	7
CREBBP	0.033	0.019	-10000	0	-10000	0	0
SKIL	0.028	0.05	-10000	0	-0.42	6	6
HDAC1	0.034	0.021	-10000	0	-0.42	1	1
HDAC2	0.031	0.023	-10000	0	-0.42	1	1
SNIP1	0.031	0.036	-10000	0	-0.42	3	3
GCN5L2	0.032	0.029	-10000	0	-0.42	1	1
SMAD3/SMAD4/TFE3	0.039	0.12	-10000	0	-0.31	36	36
MSG1/HSC70	0.031	0.062	-10000	0	-0.3	15	15
SMAD2	0.012	0.058	-10000	0	-0.15	13	13
SMAD3	0.01	0.09	-10000	0	-0.32	20	20
SMAD3/E2F4-5/DP1/p107/SMAD4	-0.001	0.078	-10000	0	-0.24	36	36
SMAD2/SMAD2/SMAD4	-0.001	0.062	0.24	5	-0.21	20	25
NCOR1	0.032	0.011	-10000	0	-10000	0	0
NCOA2	0.025	0.047	-10000	0	-0.42	5	5
NCOA1	0.031	0.045	-10000	0	-0.42	5	5
MYOD/E2A	0.03	0.08	-10000	0	-0.3	27	27
SMAD2-3/SMAD4/SP1/MIZ-1	0.037	0.18	-10000	0	-0.34	56	56
IFNB1	-0.005	0.095	0.36	1	-0.31	25	26
SMAD3/SMAD4/MEF2C	-0.003	0.17	-10000	0	-0.4	49	49
CITED1	0.029	0.031	-10000	0	-0.42	2	2
SMAD2-3/SMAD4/ARC105	0.022	0.12	-10000	0	-0.24	47	47
RBL1	0.032	0.022	-10000	0	-0.42	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.003	0.12	-10000	0	-0.4	33	33
RUNX1-3/PEBPB2	0.012	0.12	-10000	0	-0.26	71	71
SMAD7	-0.04	0.2	-10000	0	-0.52	52	52
MYC/MIZ-1	0.015	0.083	0.19	5	-0.3	29	34
SMAD3/SMAD4	0.041	0.13	0.31	42	-0.4	17	59
IL10	-0.034	0.12	-10000	0	-0.32	45	45
PIASy/HDAC complex	0.023	0.043	-10000	0	-0.42	3	3
PIAS3	0.036	0.011	-10000	0	-10000	0	0
CDK2	0.035	0.033	-10000	0	-0.42	2	2
IL5	-0.034	0.13	-10000	0	-0.28	79	79
CDK4	0.037	0.017	-10000	0	-10000	0	0
PIAS4	0.023	0.043	-10000	0	-0.42	3	3
ATF3	0.011	0.085	-10000	0	-0.42	18	18
SMAD3/SMAD4/SP1	0.016	0.16	-10000	0	-0.33	69	69
FOXG1	-0.001	0.003	-10000	0	-10000	0	0
FOXO3	0.005	0.032	-10000	0	-0.25	4	4
FOXO1	0.005	0.032	-10000	0	-0.25	4	4
FOXO4	0.005	0.032	-10000	0	-0.25	4	4
heart looping	-0.029	0.14	0.34	3	-0.34	57	60
CEBPB	0.024	0.053	-10000	0	-0.42	6	6
SMAD3/SMAD4/DLX1	0.033	0.1	-10000	0	-0.26	30	30
MYOD1	0.013	0.097	-10000	0	-0.42	24	24
SMAD3/SMAD4/HNF4	0.032	0.11	-10000	0	-0.26	31	31
SMAD3/SMAD4/GATA3	-0.01	0.17	-10000	0	-0.3	103	103
SnoN/SIN3/HDAC complex/NCoR1	0.028	0.05	-10000	0	-0.42	6	6
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.016	0.15	-10000	0	-0.28	79	79
SMAD3/SMAD4/SP1-3	0.031	0.18	-10000	0	-0.36	63	63
MED15	0	0	-10000	0	-10000	0	0
SP1	0.01	0.075	-10000	0	-0.19	38	38
SIN3B	0.035	0.005	-10000	0	-10000	0	0
SIN3A	0.034	0.007	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.034	0.15	-10000	0	-0.26	91	91
ITGB5	-0.045	0.18	-10000	0	-0.49	59	59
TGIF/SIN3/HDAC complex/CtBP	0.017	0.06	-10000	0	-0.29	9	9
SMAD3/SMAD4/AR	-0.023	0.17	-10000	0	-0.31	115	115
AR	-0.054	0.18	-10000	0	-0.42	99	99
negative regulation of cell growth	0.011	0.099	-10000	0	-0.33	22	22
SMAD3/SMAD4/MYOD	0.018	0.12	-10000	0	-0.26	56	56
E2F5	0.011	0.087	-10000	0	-0.42	19	19
E2F4	0.029	0.014	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.047	0.13	-10000	0	-0.22	69	69
SMAD2-3/SMAD4/FOXO1-3a-4	-0.003	0.099	-10000	0	-0.29	44	44
TFDP1	0.032	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.008	0.2	-10000	0	-0.39	83	83
SMAD3/SMAD4/RUNX2	0.031	0.11	-10000	0	-0.28	32	32
TGIF2	0.027	0.054	-10000	0	-0.42	7	7
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	0.036	0.003	-10000	0	-10000	0	0

×

TCGA08_retinoblastoma

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.021	0.065	-10000	0	-0.39	11	11
CDKN2C	0.023	0.065	-10000	0	-0.39	11	11
CDKN2A	0.018	0.072	-10000	0	-0.39	14	14
CCND2	0.003	0.046	0.18	27	-0.13	2	29
RB1	-0.011	0.061	0.24	2	-0.21	38	40
CDK4	0.007	0.055	0.21	29	-10000	0	29
CDK6	0.004	0.058	0.22	28	-0.17	6	34
G1/S progression	0.018	0.075	0.21	56	-0.26	3	59

×

Caspase cascade in apoptosis

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
TOP1	-0.005	0.11	0.24	1	-0.49	10	11
ACTA1	-0.016	0.13	0.23	11	-0.33	39	50
NUMA1	-0.014	0.12	-10000	0	-0.43	15	15
SPTAN1	-0.021	0.12	0.24	8	-0.32	47	55
LIMK1	-0.033	0.13	0.23	3	-0.34	50	53
BIRC3	-0.01	0.12	-10000	0	-0.42	42	42
BIRC2	0.031	0.012	-10000	0	-10000	0	0
BAX	0.035	0.007	-10000	0	-10000	0	0
CASP10	-0.049	0.092	-10000	0	-0.27	75	75
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	-0.01	0.12	0.26	1	-0.49	12	13
DIABLO	0.036	0.004	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.02	0.12	0.24	8	-0.31	47	55
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.029	0.054	-10000	0	-0.42	7	7
GSN	-0.028	0.13	0.27	4	-0.33	51	55
MADD	0.035	0.005	-10000	0	-10000	0	0
TFAP2A	0.001	0.16	-10000	0	-0.57	30	30
BID	-0.022	0.07	-10000	0	-0.18	82	82
MAP3K1	-0.033	0.14	-10000	0	-0.42	49	49
TRADD	0.029	0.014	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.047	0.037	-10000	0	-0.3	5	5
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.03	0.13	0.32	5	-0.34	51	56
CASP9	0.034	0.022	-10000	0	-0.42	1	1
DNA repair	-0.023	0.069	0.25	12	-0.17	24	36
neuron apoptosis	-0.03	0.19	-10000	0	-0.67	41	41
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.018	0.12	-10000	0	-0.42	17	17
APAF1	0.032	0.041	-10000	0	-0.42	4	4
CASP6	-0.013	0.15	-10000	0	-0.78	14	14
TRAF2	0.033	0.029	-10000	0	-0.42	2	2
ICAD/CAD	-0.024	0.12	0.26	2	-0.32	40	42
CASP7	0.031	0.1	0.26	45	-0.32	14	59
KRT18	-0.067	0.22	-10000	0	-0.57	74	74
apoptosis	-0.016	0.12	0.28	3	-0.39	21	24
DFFA	-0.023	0.12	0.23	4	-0.32	46	50
DFFB	-0.023	0.12	0.23	3	-0.32	46	49
PARP1	0.023	0.07	0.17	23	-0.25	12	35
actin filament polymerization	0.033	0.13	0.33	46	-0.3	7	53
TNF	0.026	0.061	-10000	0	-0.42	9	9
CYCS	-0.008	0.056	0.14	8	-0.2	10	18
SATB1	-0.027	0.15	-10000	0	-0.7	16	16
SLK	-0.023	0.12	0.25	4	-0.32	47	51
p15 BID/BAX	-0.002	0.077	-10000	0	-0.25	15	15
CASP2	-0.016	0.1	0.22	5	-0.32	30	35
JNK cascade	0.033	0.14	0.41	49	-10000	0	49
CASP3	-0.021	0.13	0.23	5	-0.33	50	55
LMNB2	-0.009	0.12	0.24	1	-0.42	21	22
RIPK1	0.035	0.007	-10000	0	-10000	0	0
CASP4	0.023	0.061	-10000	0	-0.42	9	9
Mammalian IAPs/DIABLO	0.032	0.084	-10000	0	-0.23	41	41
negative regulation of DNA binding	0.001	0.15	-10000	0	-0.57	30	30
stress fiber formation	-0.023	0.12	0.24	4	-0.31	47	51
GZMB	-0.034	0.12	-10000	0	-0.31	75	75
CASP1	-0.009	0.1	-10000	0	-0.36	33	33
LMNB1	-0.06	0.16	-10000	0	-0.4	44	44
APP	-0.031	0.2	-10000	0	-0.68	41	41
TNFRSF1A	0.033	0.022	-10000	0	-0.42	1	1
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.009	0.001	-10000	0	-10000	0	0
VIM	-0.012	0.13	0.29	2	-0.4	22	24
LMNA	-0.008	0.098	0.24	1	-0.32	18	19
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.017	0.11	-10000	0	-0.34	33	33
LRDD	0.035	0.007	-10000	0	-10000	0	0
SREBF1	-0.036	0.13	0.25	2	-0.33	47	49
APAF-1/Caspase 9	0.016	0.12	-10000	0	-0.64	13	13
nuclear fragmentation during apoptosis	-0.013	0.12	-10000	0	-0.43	15	15
CFL2	-0.034	0.13	0.3	7	-0.33	48	55
GAS2	-0.031	0.13	0.24	5	-0.33	51	56
positive regulation of apoptosis	-0.028	0.12	0.26	1	-0.39	23	24
PRF1	0.026	0.058	-10000	0	-0.42	8	8

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.046	0.1	-9999	-0.24	46	46
SMAD6-7/SMURF1	0.067	0.024	-9999	-0.26	1	1
NOG	0.029	0.037	-9999	-0.42	3	3
SMAD9	-0.028	0.16	-9999	-0.45	53	53
SMAD4	0.028	0.054	-9999	-0.42	7	7
SMAD5	-0.028	0.12	-9999	-0.34	39	39
BMP7/USAG1	-0.064	0.16	-9999	-0.31	140	140
SMAD5/SKI	-0.016	0.13	-9999	-0.39	29	29
SMAD1	0.011	0.07	-9999	-0.32	6	6
BMP2	0.021	0.07	-9999	-0.42	12	12
SMAD1/SMAD1/SMAD4	0.033	0.078	-9999	-0.29	5	5
BMPR1A	0.031	0.046	-9999	-0.42	5	5
BMPR1B	-0.004	0.11	-9999	-0.42	30	30
BMPR1A-1B/BAMBI	-0.021	0.14	-9999	-0.26	120	120
AHSG	0.034	0.008	-9999	-10000	0	0
CER1	0.034	0.009	-9999	-10000	0	0
BMP2-4/CER1	0.014	0.12	-9999	-0.26	71	71
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.017	0.13	-9999	-0.35	35	35
BMP2-4 (homodimer)	-0.007	0.13	-9999	-0.31	74	74
RGMB	0.026	0.061	-9999	-0.42	9	9
BMP6/BMPR2/BMPR1A-1B	0.05	0.091	-9999	-0.24	41	41
RGMA	0.019	0.073	-9999	-0.42	13	13
SMURF1	0.035	0.006	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.031	0.12	-9999	-0.38	31	31
BMP2-4/USAG1	-0.079	0.17	-9999	-0.29	192	192
SMAD6/SMURF1/SMAD5	-0.015	0.13	-9999	-0.39	28	28
SOSTDC1	-0.12	0.2	-9999	-0.42	155	155
BMP7/BMPR2/BMPR1A-1B	0.04	0.095	-9999	-0.24	45	45
SKI	0.036	0.002	-9999	-10000	0	0
BMP6 (homodimer)	0.027	0.05	-9999	-0.42	6	6
HFE2	0.026	0.064	-9999	-0.42	10	10
ZFYVE16	0.033	0.03	-9999	-0.42	2	2
MAP3K7	0.033	0.01	-9999	-10000	0	0
BMP2-4/CHRD	0.012	0.12	-9999	-0.28	70	70
SMAD5/SMAD5/SMAD4	-0.019	0.13	-9999	-0.38	32	32
MAPK1	0.033	0.022	-9999	-0.42	1	1
TAK1/TAB family	0.013	0.14	-9999	-0.37	24	24
BMP7 (homodimer)	0.015	0.073	-9999	-0.42	13	13
NUP214	0.035	0.021	-9999	-0.42	1	1
BMP6/FETUA	0.044	0.041	-9999	-0.3	6	6
SMAD1/SKI	0.026	0.08	-9999	-0.31	8	8
SMAD6	0.035	0.007	-9999	-10000	0	0
CTDSP2	0.034	0.029	-9999	-0.42	2	2
BMP2-4/FETUA	0.015	0.12	-9999	-0.26	69	69
MAP3K7IP1	0.034	0.009	-9999	-10000	0	0
GREM1	-0.003	0.12	-9999	-0.42	40	40
BMPR2 (homodimer)	0.034	0.029	-9999	-0.42	2	2
GADD34/PP1CA	0.059	0.041	-9999	-0.26	5	5
BMPR1A-1B (homodimer)	0.019	0.087	-9999	-0.3	34	34
CHRDL1	0.03	0.037	-9999	-0.42	3	3
ENDOFIN/SMAD1	0.025	0.08	-9999	-0.32	7	7
SMAD6-7/SMURF1/SMAD1	0.055	0.085	-9999	-0.31	5	5
SMAD6/SMURF1	0.035	0.006	-9999	-10000	0	0
BAMBI	-0.055	0.18	-9999	-0.42	93	93
SMURF2	0.028	0.042	-9999	-0.42	4	4
BMP2-4/CHRDL1	0.012	0.12	-9999	-0.27	75	75
BMP2-4/GREM1	-0.011	0.15	-9999	-0.29	102	102
SMAD7	0.034	0.021	-9999	-0.42	1	1
SMAD8A/SMAD8A/SMAD4	-0.022	0.17	-9999	-0.44	58	58
SMAD1/SMAD6	0.025	0.08	-9999	-0.31	8	8
TAK1/SMAD6	0.048	0.016	-9999	-10000	0	0
BMP7	0.015	0.073	-9999	-0.42	13	13
BMP6	0.027	0.05	-9999	-0.42	6	6
MAP3K7IP2	0.031	0.03	-9999	-0.42	2	2
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.02	0.12	-9999	-0.34	35	35
PPM1A	0.034	0.022	-9999	-0.42	1	1
SMAD1/SMURF2	0.021	0.076	-9999	-0.32	6	6
SMAD7/SMURF1	0.05	0.02	-9999	-0.3	1	1
CTDSPL	0.028	0.054	-9999	-0.42	7	7
PPP1CA	0.031	0.03	-9999	-0.42	2	2
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0.034	0.029	-9999	-0.42	2	2
PPP1R15A	0.034	0.021	-9999	-0.42	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.033	0.13	-9999	-0.4	35	35
CHRD	0.029	0.046	-9999	-0.42	5	5
BMPR2	0.034	0.029	-9999	-0.42	2	2
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.03	0.12	-9999	-0.39	30	30
BMP4	-0.028	0.15	-9999	-0.42	65	65
FST	0.024	0.058	-9999	-0.42	8	8
BMP2-4/NOG	0.01	0.12	-9999	-0.26	73	73
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.051	0.097	-9999	-0.23	45	45

×

Nectin adhesion pathway

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
PDGFRB	0.028	0.057	-10000	0	-0.42	8	8
alphaV beta3 Integrin	0.035	0.073	-10000	0	-0.32	20	20
PTK2	-0.025	0.14	-10000	0	-0.43	36	36
positive regulation of JNK cascade	-0.001	0.12	-10000	0	-0.31	46	46
CDC42/GDP	0.009	0.17	-10000	0	-0.42	48	48
Rac1/GDP	0.01	0.16	-10000	0	-0.41	47	47
RAP1B	0.032	0.03	-10000	0	-0.42	2	2
RAP1A	0.03	0.05	-10000	0	-0.42	6	6
CTNNB1	0.024	0.067	-10000	0	-0.42	11	11
CDC42/GTP	0.001	0.15	-10000	0	-0.39	46	46
nectin-3/I-afadin	0.022	0.097	-10000	0	-0.33	34	34
RAPGEF1	-0.015	0.16	-10000	0	-0.44	48	48
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.02	0.18	-10000	0	-0.5	48	48
PDGFB-D/PDGFRB	0.028	0.057	-10000	0	-0.42	8	8
TLN1	-0.014	0.071	0.19	4	-0.34	14	18
Rap1/GTP	-0.006	0.12	-10000	0	-0.33	45	45
IQGAP1	0.034	0.008	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.047	0.063	-10000	0	-0.23	21	21
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.022	0.097	-10000	0	-0.33	34	34
PVR	0.032	0.036	-10000	0	-0.42	3	3
Necl-5(dimer)	0.032	0.036	-10000	0	-0.42	3	3
mol:GDP	-0.012	0.19	-10000	0	-0.51	48	48
MLLT4	0.02	0.075	-10000	0	-0.42	14	14
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
PI3K	0.053	0.12	-10000	0	-0.28	48	48
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.033	0.062	-10000	0	-0.3	15	15
positive regulation of lamellipodium assembly	0.005	0.13	-10000	0	-0.32	45	45
PVRL1	0.03	0.024	-10000	0	-0.42	1	1
PVRL3	0.011	0.099	-10000	0	-0.42	25	25
PVRL2	0.026	0.064	-10000	0	-0.42	10	10
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
CDH1	-0.012	0.13	-10000	0	-0.42	45	45
CLDN1	-0.047	0.17	-10000	0	-0.42	85	85
JAM-A/CLDN1	0.002	0.13	-10000	0	-0.27	85	85
SRC	-0.033	0.19	-10000	0	-0.51	62	62
ITGB3	0.029	0.046	-10000	0	-0.42	5	5
nectin-1(dimer)/I-afadin/I-afadin	0.033	0.062	-10000	0	-0.3	15	15
FARP2	-0.015	0.2	-10000	0	-0.52	48	48
RAC1	0.035	0.006	-10000	0	-10000	0	0
CTNNA1	0.035	0.006	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.038	0.095	-10000	0	-0.29	36	36
nectin-1/I-afadin	0.033	0.062	-10000	0	-0.3	15	15
nectin-2/I-afadin	0.032	0.074	-10000	0	-0.3	23	23
RAC1/GTP/IQGAP1/filamentous actin	0.045	0.012	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.035	0.092	-10000	0	-0.28	35	35
CDC42/GTP/IQGAP1/filamentous actin	0.045	0.014	-10000	0	-10000	0	0
F11R	0.026	0.038	-10000	0	-0.42	3	3
positive regulation of filopodium formation	-0.001	0.12	-10000	0	-0.31	46	46
alphaV/beta3 Integrin/Talin	0.008	0.11	0.27	1	-0.33	27	28
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.032	0.074	-10000	0	-0.3	23	23
nectin-2(dimer)/I-afadin/I-afadin	0.032	0.074	-10000	0	-0.3	23	23
PIP5K1C	-0.01	0.074	-10000	0	-0.23	37	37
VAV2	-0.006	0.19	-10000	0	-0.52	43	43
RAP1/GDP	0.01	0.16	-10000	0	-0.39	46	46
ITGAV	0.021	0.08	-10000	0	-0.42	16	16
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.035	0.1	-10000	0	-0.28	41	41
nectin-3(dimer)/I-afadin/I-afadin	0.022	0.097	-10000	0	-0.33	34	34
Rac1/GTP	0.008	0.15	-10000	0	-0.39	45	45
PTPRM	-0.005	0.085	-10000	0	-0.26	38	38
E-cadherin/beta catenin/alpha catenin	0.025	0.12	-10000	0	-0.22	74	74
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.034	0.008	-10000	0	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.048	0.016	-10000	0	-10000	0	0
VLDLR	-0.007	0.13	-10000	0	-0.42	42	42
CRKL	0.03	0.041	-10000	0	-0.42	4	4
LRPAP1	0.035	0.007	-10000	0	-10000	0	0
FYN	0.027	0.05	-10000	0	-0.42	6	6
ITGA3	0.023	0.07	-10000	0	-0.42	12	12
RELN/VLDLR/Fyn	0.027	0.1	-10000	0	-0.27	50	50
MAPK8IP1/MKK7/MAP3K11/JNK1	0.068	0.071	-10000	0	-0.22	16	16
AKT1	-0.018	0.088	-10000	0	-0.23	58	58
MAP2K7	0.034	0.021	-10000	0	-0.42	1	1
RAPGEF1	0.036	0.004	-10000	0	-10000	0	0
DAB1	0.035	0.006	-10000	0	-10000	0	0
RELN/LRP8/DAB1	0.039	0.08	-10000	0	-0.23	39	39
LRPAP1/LRP8	0.023	0.088	-10000	0	-0.3	34	34
RELN/LRP8/DAB1/Fyn	0.045	0.088	-10000	0	-0.22	45	45
DAB1/alpha3/beta1 Integrin	0.016	0.11	-10000	0	-0.22	83	83
long-term memory	0.049	0.1	-10000	0	-0.22	54	54
DAB1/LIS1	0.032	0.12	-10000	0	-0.22	79	79
DAB1/CRLK/C3G	0.021	0.11	-10000	0	-0.22	81	81
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
DAB1/NCK2	0.039	0.12	-10000	0	-0.22	79	79
ARHGEF2	0.021	0.058	-10000	0	-0.42	8	8
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.032	0.011	-10000	0	-10000	0	0
CDK5R1	0.033	0.01	-10000	0	-10000	0	0
RELN	0.03	0.046	-10000	0	-0.42	5	5
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
RELN/LRP8/Fyn	0.032	0.093	-10000	0	-0.26	45	45
GRIN2A/RELN/LRP8/DAB1/Fyn	0.055	0.092	-10000	0	-0.22	39	39
MAPK8	0.033	0.035	-10000	0	-0.42	3	3
RELN/VLDLR/DAB1	0.032	0.088	-10000	0	-0.24	46	46
ITGB1	0.033	0.03	-10000	0	-0.42	2	2
MAP1B	-0.027	0.12	0.32	5	-0.24	95	100
RELN/LRP8	0.038	0.088	-10000	0	-0.26	39	39
GRIN2B/RELN/LRP8/DAB1/Fyn	0.046	0.11	-10000	0	-0.23	62	62
PI3K	0.035	0.067	-10000	0	-0.3	18	18
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.04	0.057	-10000	0	-0.32	11	11
RAP1A	-0.043	0.097	0.34	7	-0.44	3	10
PAFAH1B1	0.032	0.023	-10000	0	-0.42	1	1
MAPK8IP1	0.033	0.029	-10000	0	-0.42	2	2
CRLK/C3G	0.047	0.034	-10000	0	-0.3	4	4
GRIN2B	0.016	0.087	-10000	0	-0.42	19	19
NCK2	0.036	0.004	-10000	0	-10000	0	0
neuron differentiation	0.018	0.081	-10000	0	-0.34	6	6
neuron adhesion	-0.043	0.1	0.35	7	-0.4	5	12
LRP8	0	0.11	-10000	0	-0.42	34	34
GSK3B	-0.016	0.092	0.19	5	-0.41	10	15
RELN/VLDLR/DAB1/Fyn	0.039	0.096	-10000	0	-0.23	50	50
MAP3K11	0.033	0.029	-10000	0	-0.42	2	2
RELN/VLDLR/DAB1/P13K	-0.007	0.096	-10000	0	-0.24	61	61
CDK5	0.035	0.007	-10000	0	-10000	0	0
MAPT	-0.071	0.17	0.79	4	-0.39	96	100
neuron migration	-0.025	0.11	0.29	11	-0.32	21	32
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.017	0.081	-10000	0	-0.34	6	6
RELN/VLDLR	0.025	0.12	-10000	0	-0.24	79	79

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.004	0.11	-10000	0	-0.31	50	50
VEGFR1 homodimer/NRP1	-0.016	0.1	-10000	0	-0.3	50	50
mol:DAG	-0.009	0.1	-10000	0	-0.28	49	49
VEGFR1 homodimer/NRP1/VEGFR 121	-0.014	0.095	-10000	0	-0.28	50	50
CaM/Ca2+	0.009	0.1	-10000	0	-0.27	47	47
HIF1A	-0.005	0.14	-10000	0	-0.42	51	51
GAB1	0.027	0.061	-10000	0	-0.42	9	9
AKT1	-0.016	0.1	-10000	0	-0.44	15	15
PLCG1	-0.009	0.1	-10000	0	-0.28	49	49
NOS3	0.002	0.11	0.38	2	-0.47	15	17
CBL	0.031	0.012	-10000	0	-10000	0	0
mol:NO	0.005	0.11	0.34	4	-0.46	15	19
FLT1	-0.013	0.12	-10000	0	-0.37	45	45
PGF	0.031	0.041	-10000	0	-0.42	4	4
VEGFR1 homodimer/NRP2/VEGFR121	0.004	0.1	-10000	0	-0.29	50	50
CALM1	0.035	0.007	-10000	0	-10000	0	0
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
eNOS/Hsp90	-0.002	0.1	0.27	1	-0.44	15	16
endothelial cell proliferation	0	0.11	0.3	9	-0.42	15	24
mol:Ca2+	-0.009	0.1	-10000	0	-0.28	49	49
MAPK3	-0.024	0.08	0.35	1	-0.48	9	10
MAPK1	-0.028	0.083	0.35	1	-0.49	8	9
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
PLGF homodimer	0.031	0.041	-10000	0	-0.42	4	4
PRKACA	0.036	0.004	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.028	0.05	-10000	0	-0.42	6	6
VEGFA homodimer	0	0	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	-0.016	0.1	-10000	0	-0.3	50	50
platelet activating factor biosynthetic process	-0.003	0.1	0.33	6	-0.45	9	15
PI3K	0.027	0.13	-10000	0	-0.27	66	66
PRKCA	-0.027	0.09	0.2	11	-0.28	37	48
PRKCB	-0.028	0.091	0.18	13	-0.27	45	58
VEGFR1 homodimer/PLGF homodimer	0.003	0.12	-10000	0	-0.31	53	53
VEGFA	0	0	-10000	0	-10000	0	0
VEGFB	0.034	0.021	-10000	0	-0.42	1	1
mol:IP3	-0.009	0.1	-10000	0	-0.28	49	49
RASA1	-0.012	0.11	-10000	0	-0.29	55	55
NRP2	0.034	0.021	-10000	0	-0.42	1	1
VEGFR1 homodimer	-0.013	0.12	-10000	0	-0.37	45	45
VEGFB homodimer	0.034	0.021	-10000	0	-0.42	1	1
NCK1	0.034	0.022	-10000	0	-0.42	1	1
eNOS/Caveolin-1	0.017	0.12	0.36	3	-0.48	15	18
PTPN11	0.036	0.004	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.025	0.13	-10000	0	-0.27	66	66
mol:L-citrulline	0.005	0.11	0.34	4	-0.46	15	19
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.018	0.1	-10000	0	-0.27	49	49
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.003	0.1	-10000	0	-0.28	51	51
CD2AP	0.035	0.007	-10000	0	-10000	0	0
PI3K/GAB1	0.033	0.13	-10000	0	-0.32	31	31
PDPK1	-0.026	0.1	0.34	1	-0.46	11	12
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.005	0.1	-10000	0	-0.28	50	50
mol:NADP	0.005	0.11	0.34	4	-0.46	15	19
HSP90AA1	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.016	0.1	-10000	0	-0.26	49	49
VEGFR1 homodimer/NRP2	0.004	0.11	-10000	0	-0.31	50	50

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.03	0.046	-10000	0	-0.42	5	5
GNAT1/GTP	0.023	0.025	-10000	0	-0.3	3	3
Metarhodopsin II/Arrestin	0.008	0.094	-10000	0	-0.25	57	57
PDE6G/GNAT1/GTP	0.041	0.028	-10000	0	-0.25	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.032	0.036	-10000	0	-0.42	3	3
GRK1	0	0	-10000	0	-10000	0	0
CNG Channel	-0.018	0.12	-10000	0	-0.22	125	125
mol:Na +	0.023	0.098	-10000	0	-0.24	47	47
mol:ADP	0	0	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.007	0.12	-10000	0	-0.27	72	72
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.034	0.11	-10000	0	-0.27	30	30
CNGB1	0.03	0.014	-10000	0	-10000	0	0
RDH5	0.033	0.01	-10000	0	-10000	0	0
SAG	-0.024	0.14	-10000	0	-0.42	58	58
mol:Ca2+	-0.034	0.091	0.35	8	-0.4	9	17
Na + (4 Units)	0.014	0.093	-10000	0	-0.37	10	10
RGS9	0.017	0.067	-10000	0	-0.42	11	11
GNB1/GNGT1	0.034	0.064	-10000	0	-0.3	17	17
GNAT1/GDP	0.019	0.11	-10000	0	-0.23	75	75
GUCY2D	0.032	0.012	-10000	0	-10000	0	0
GNGT1	0.016	0.07	-10000	0	-0.42	12	12
GUCY2F	0.027	0.064	-10000	0	-0.42	10	10
GNB5	0.024	0.067	-10000	0	-0.42	11	11
mol:GMP (4 units)	-0.022	0.1	-10000	0	-0.22	107	107
mol:11-cis-retinal	0.033	0.01	-10000	0	-10000	0	0
mol:cGMP	0.047	0.084	-10000	0	-0.26	29	29
GNB1	0.032	0.045	-10000	0	-0.42	5	5
Rhodopsin	0.05	0.011	-10000	0	-10000	0	0
SLC24A1	0.03	0.046	-10000	0	-0.42	5	5
CNGA1	0.003	0.11	-10000	0	-0.42	29	29
Metarhodopsin II	0.023	0.004	-10000	0	-10000	0	0
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.063	0.077	-10000	0	-0.25	23	23
RGS9BP	-0.022	0.15	-10000	0	-0.42	60	60
Metarhodopsin II/Transducin	0.014	0.049	-10000	0	-0.22	21	21
GCAP Family/Ca ++	0.05	0.069	-10000	0	-0.25	23	23
PDE6A/B	-0.028	0.15	-10000	0	-0.3	113	113
mol:Pi	0.007	0.12	-10000	0	-0.27	72	72
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.048	0.06	-10000	0	-0.23	20	20
PDE6B	-0.066	0.19	-10000	0	-0.42	112	112
PDE6A	0.033	0.029	-10000	0	-0.42	2	2
PDE6G	0.033	0.01	-10000	0	-10000	0	0
RHO	0.035	0.005	-10000	0	-10000	0	0
PDE6	-0.016	0.15	-10000	0	-0.24	141	141
GUCA1A	0.022	0.075	-10000	0	-0.42	14	14
GC2/GCAP Family	0.066	0.09	-10000	0	-0.28	29	29
GUCA1C	0.026	0.064	-10000	0	-0.42	10	10
GUCA1B	0.034	0.022	-10000	0	-0.42	1	1

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.008	0.035	-10000	0	-0.097	62	62
STMN1	0.005	0.051	-10000	0	-0.34	10	10
Aurora B/RasGAP/Survivin	0.027	0.1	-10000	0	-0.28	44	44
Chromosomal passenger complex/Cul3 protein complex	-0.046	0.12	-10000	0	-0.25	101	101
BIRC5	-0.004	0.13	-10000	0	-0.44	38	38
DES	-0.065	0.26	-10000	0	-0.67	74	74
Aurora C/Aurora B/INCENP	0.052	0.051	-10000	0	-0.24	11	11
Aurora B/TACC1	0.023	0.063	-10000	0	-0.26	22	22
Aurora B/PP2A	0.044	0.034	-10000	0	-0.32	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.008	0.025	-10000	0	-0.19	7	7
mitotic metaphase/anaphase transition	0.001	0.005	0.015	47	-0.01	3	50
NDC80	0.004	0.026	-10000	0	-0.31	3	3
Cul3 protein complex	0.014	0.12	-10000	0	-0.26	76	76
KIF2C	-0.057	0.22	-10000	0	-0.66	50	50
PEBP1	-0.001	0.004	0.012	1	-0.014	38	39
KIF20A	0.004	0.12	-10000	0	-0.43	35	35
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.039	0.053	-10000	0	-0.31	10	10
SEPT1	0.031	0.023	-10000	0	-0.42	1	1
SMC2	0	0	-10000	0	-10000	0	0
SMC4	0	0	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.046	0.18	-10000	0	-0.51	62	62
PSMA3	0.035	0.006	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.004	0.01	54	-0.009	8	62
H3F3B	0.013	0.028	-10000	0	-0.3	4	4
AURKB	0.028	0.04	-10000	0	-0.45	3	3
AURKC	0.034	0.021	-10000	0	-0.42	1	1
CDCA8	0.015	0.09	-10000	0	-0.45	18	18
cytokinesis	-0.046	0.23	-10000	0	-0.65	49	49
Aurora B/Septin1	-0.029	0.22	-10000	0	-0.61	46	46
AURKA	0	0.004	0.01	54	-0.009	8	62
INCENP	0.024	0.058	-10000	0	-0.44	7	7
KLHL13	-0.035	0.16	-10000	0	-0.42	73	73
BUB1	-0.011	0.14	-10000	0	-0.43	51	51
hSgo1/Aurora B/Survivin	0.024	0.12	-10000	0	-0.34	39	39
EVI5	0.031	0.041	-10000	0	-0.42	4	4
RhoA/GTP	-0.023	0.22	-10000	0	-0.57	53	53
SGOL1	0.02	0.08	-10000	0	-0.42	16	16
CENPA	-0.041	0.15	-10000	0	-0.38	60	60
NCAPG	0	0	-10000	0	-10000	0	0
Aurora B/HC8 Proteasome	0.044	0.034	-10000	0	-0.32	3	3
NCAPD2	0	0	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.043	0.043	-10000	0	-0.31	6	6
RHOA	0.026	0.061	-10000	0	-0.42	9	9
NCAPH	0	0	-10000	0	-10000	0	0
NPM1	-0.021	0.12	-10000	0	-0.33	48	48
RASA1	0.028	0.054	-10000	0	-0.42	7	7
KLHL9	0.032	0.03	-10000	0	-0.42	2	2
mitotic prometaphase	-0.001	0.004	0.012	1	-0.014	38	39
proteasomal ubiquitin-dependent protein catabolic process	0.044	0.034	-10000	0	-0.32	3	3
PPP1CC	0.033	0.035	-10000	0	-0.42	3	3
Centraspindlin	-0.032	0.24	-10000	0	-0.61	54	54
RhoA/GDP	0.02	0.043	-10000	0	-0.3	9	9
NSUN2	-0.018	0.11	-10000	0	-0.32	47	47
MYLK	0.006	0.057	-10000	0	-0.31	16	16
KIF23	0.006	0.11	-10000	0	-0.44	30	30
VIM	-0.006	0.072	-10000	0	-0.31	27	27
RACGAP1	0.019	0.085	-10000	0	-0.44	17	17
mitosis	0	0	-10000	0	-10000	0	0
NCL	-0.023	0.13	-10000	0	-0.34	58	58
Chromosomal passenger complex	-0.05	0.19	-10000	0	-0.47	61	61
Chromosomal passenger complex/EVI5	0.037	0.14	-10000	0	-0.34	48	48
TACC1	0.012	0.087	-10000	0	-0.42	19	19
PPP2R5D	0.035	0.007	-10000	0	-10000	0	0
CUL3	0.032	0.041	-10000	0	-0.42	4	4
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.026	0.004	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAP3K7IP2	0.031	0.03	-10000	0	-0.42	2	2
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.01	0.11	-10000	0	-0.37	29	29
IRAK/TOLLIP	0.04	0.017	0.18	5	-10000	0	5
IKBKB	0.029	0.014	-10000	0	-10000	0	0
IKBKG	0.036	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0.024	0.092	-10000	0	-0.3	37	37
IL1A	0.031	0.041	-10000	0	-0.42	4	4
IL1B	-0.025	0.11	-10000	0	-0.34	54	54
IRAK/TRAF6/p62/Atypical PKCs	0.059	0.049	-10000	0	-0.21	12	12
IL1R2	0.002	0.11	-10000	0	-0.42	33	33
IL1R1	-0.005	0.13	-10000	0	-0.42	43	43
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.022	0.12	-10000	0	-0.4	29	29
TOLLIP	0.035	0.007	-10000	0	-10000	0	0
TICAM2	0	0	-10000	0	-10000	0	0
MAP3K3	0.031	0.012	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.06	0.034	-10000	0	-0.26	2	2
IKK complex/ELKS	0.025	0.077	0.27	1	-0.31	9	10
JUN	-0.029	0.072	0.28	4	-0.45	2	6
MAP3K7	0.033	0.01	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.005	0.15	-10000	0	-0.28	95	95
IL1 alpha/IL1R1/IL1RAP/MYD88	0.052	0.098	-10000	0	-0.23	50	50
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.063	0.1	-10000	0	-0.22	53	53
IL1 beta fragment/IL1R1/IL1RAP	-0.012	0.14	-10000	0	-0.29	87	87
NFKB1	0.035	0.005	-10000	0	-10000	0	0
MAPK8	-0.014	0.063	0.28	6	-0.38	1	7
IRAK1	0.018	0.003	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.003	0.13	-10000	0	-0.32	72	72
IRAK4	0.033	0.035	-10000	0	-0.42	3	3
PRKCI	0.024	0.067	-10000	0	-0.42	11	11
TRAF6	0.034	0.021	-10000	0	-0.42	1	1
PI3K	0.035	0.067	-10000	0	-0.3	18	18
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.019	0.13	-10000	0	-0.38	39	39
CHUK	0.025	0.067	-10000	0	-0.42	11	11
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.012	0.14	-10000	0	-0.29	87	87
IL1 beta/IL1R2	-0.021	0.13	-10000	0	-0.3	86	86
IRAK/TRAF6/TAK1/TAB1/TAB2	0.074	0.045	-10000	0	-0.21	3	3
NF kappa B1 p50/RelA	-0.005	0.14	-10000	0	-0.27	92	92
IRAK3	0.026	0.047	-10000	0	-0.42	5	5
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0	0.13	-10000	0	-0.27	88	88
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.006	0.085	-10000	0	-0.23	53	53
IL1 alpha/IL1R1/IL1RAP	0.037	0.095	-10000	0	-0.26	46	46
RELA	0.035	0.006	-10000	0	-10000	0	0
MAP3K7IP1	0.034	0.009	-10000	0	-10000	0	0
SQSTM1	0.034	0.021	-10000	0	-0.42	1	1
MYD88	0.031	0.041	-10000	0	-0.42	4	4
IRAK/TRAF6/MEKK3	0.053	0.029	-10000	0	-0.22	1	1
IL1RAP	0.033	0.022	-10000	0	-0.42	1	1
UBE2N	0.035	0.005	-10000	0	-10000	0	0
IRAK/TRAF6	-0.016	0.11	-10000	0	-0.25	81	81
CASP1	0.001	0.11	-10000	0	-0.42	31	31
IL1RN/IL1R2	0.002	0.13	-10000	0	-0.32	63	63
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.002	0.14	-10000	0	-0.28	88	88
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.003	0.11	-10000	0	-0.32	45	45
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
IL1RN	0	0.12	-10000	0	-0.42	37	37
TRAF6/TAK1/TAB1/TAB2	0.071	0.043	-10000	0	-0.22	3	3
MAP2K6	-0.01	0.062	0.29	5	-0.4	1	6

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.025	0.16	0.25	4	-0.42	48	52
IKBKB	0.017	0.09	0.33	2	-0.3	4	6
AKT1	0.022	0.11	0.24	43	-0.23	18	61
IKBKG	0.026	0.079	0.24	5	-0.28	6	11
CALM1	-0.012	0.13	0.25	5	-0.42	26	31
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
MAP3K1	-0.022	0.18	0.32	2	-0.5	40	42
MAP3K7	0.033	0.01	-10000	0	-10000	0	0
mol:Ca2+	-0.012	0.14	0.27	5	-0.42	29	34
DOK1	0.027	0.061	-10000	0	-0.42	9	9
AP-1	-0.021	0.1	0.2	4	-0.25	46	50
LYN	0.03	0.014	-10000	0	-10000	0	0
BLNK	0.012	0.1	-10000	0	-0.42	26	26
SHC1	0.027	0.025	-10000	0	-0.42	1	1
BCR complex	0.024	0.076	-10000	0	-0.3	24	24
CD22	-0.021	0.12	0.26	1	-0.49	25	26
CAMK2G	-0.011	0.12	0.24	7	-0.41	24	31
CSNK2A1	0.034	0.008	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.003	0.079	-10000	0	-0.25	35	35
GO:0007205	-0.012	0.14	0.27	5	-0.43	29	34
SYK	0.005	0.11	-10000	0	-0.42	33	33
ELK1	-0.014	0.13	0.25	5	-0.42	27	32
NFATC1	0.019	0.14	0.26	21	-0.38	30	51
B-cell antigen/BCR complex	0.024	0.076	-10000	0	-0.3	24	24
PAG1/CSK	0.034	0.051	-10000	0	-0.3	9	9
NFKBIB	0.027	0.05	0.15	9	-0.12	21	30
HRAS	0.002	0.12	0.24	17	-0.35	26	43
NFKBIA	0.028	0.049	0.15	9	-0.12	19	28
NF-kappa-B/RelA/I kappa B beta	0.032	0.044	0.15	9	-10000	0	9
RasGAP/Csk	0.037	0.1	-10000	0	-0.27	35	35
mol:GDP	-0.011	0.13	0.26	5	-0.4	32	37
PTEN	0.027	0.061	-10000	0	-0.42	9	9
CD79B	0.006	0.097	-10000	0	-0.42	24	24
NF-kappa-B/RelA/I kappa B alpha	0.032	0.044	0.15	9	-10000	0	9
GRB2	0.033	0.01	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.011	0.18	0.33	3	-0.5	40	43
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
mol:IP3	-0.013	0.14	0.27	4	-0.44	29	33
CSK	0.033	0.022	-10000	0	-0.42	1	1
FOS	-0.038	0.14	0.24	4	-0.39	42	46
CHUK	0.015	0.099	0.24	5	-0.32	21	26
IBTK	0.032	0.03	-10000	0	-0.42	2	2
CARD11/BCL10/MALT1/TAK1	0.009	0.13	0.27	1	-0.4	25	26
PTPN6	-0.012	0.12	0.25	1	-0.48	24	25
RELA	0.035	0.006	-10000	0	-10000	0	0
BCL2A1	0.023	0.035	0.14	2	-10000	0	2
VAV2	-0.002	0.14	0.26	3	-0.51	25	28
ubiquitin-dependent protein catabolic process	0.03	0.049	0.15	9	-0.12	21	30
BTK	-0.012	0.19	-10000	0	-1.1	15	15
CD19	-0.019	0.12	0.26	1	-0.47	27	28
MAP4K1	0.035	0.007	-10000	0	-10000	0	0
CD72	0.008	0.1	-10000	0	-0.42	27	27
PAG1	0.02	0.061	-10000	0	-0.42	9	9
MAPK14	-0.017	0.16	0.3	2	-0.43	37	39
SH3BP5	0.021	0.078	-10000	0	-0.42	15	15
PIK3AP1	-0.021	0.15	0.28	4	-0.46	35	39
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.02	0.16	-10000	0	-0.52	33	33
RAF1	0.002	0.11	0.24	13	-0.35	22	35
RasGAP/p62DOK/SHIP	0.026	0.1	-10000	0	-0.27	39	39
CD79A	0.031	0.023	-10000	0	-0.42	1	1
re-entry into mitotic cell cycle	-0.02	0.1	0.2	4	-0.25	45	49
RASA1	0.028	0.054	-10000	0	-0.42	7	7
MAPK3	0.012	0.11	0.26	15	-0.31	15	30
MAPK1	0.001	0.1	0.26	8	-0.33	16	24
CD72/SHP1	0.016	0.16	0.29	17	-0.46	31	48
NFKB1	0.035	0.005	-10000	0	-10000	0	0
MAPK8	-0.018	0.16	0.29	6	-0.43	38	44
actin cytoskeleton organization	0.017	0.14	0.3	11	-0.46	24	35
NF-kappa-B/RelA	0.065	0.087	0.27	9	-0.27	3	12
Calcineurin	0.003	0.13	0.25	1	-0.38	27	28
PI3K	-0.027	0.11	-10000	0	-0.39	29	29
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.012	0.15	0.3	4	-0.44	36	40
SOS1	0.034	0.021	-10000	0	-0.42	1	1
Bam32/HPK1	-0.068	0.31	-10000	0	-0.74	78	78
DAPP1	-0.1	0.34	-10000	0	-0.84	78	78
cytokine secretion	0.02	0.13	0.25	24	-0.35	30	54
mol:DAG	-0.013	0.14	0.27	4	-0.44	29	33
PLCG2	0.02	0.055	-10000	0	-0.42	7	7
MAP2K1	0.001	0.11	0.24	10	-0.35	17	27
B-cell antigen/BCR complex/FcgammaRIIB	0.02	0.093	-10000	0	-0.3	33	33
mol:PI-3-4-5-P3	-0.001	0.11	0.23	24	-0.3	26	50
ETS1	-0.011	0.11	0.23	7	-0.38	24	31
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.032	0.12	-10000	0	-0.26	56	56
B-cell antigen/BCR complex/LYN	-0.014	0.12	0.27	1	-0.45	32	33
MALT1	0.031	0.041	-10000	0	-0.42	4	4
TRAF6	0.034	0.021	-10000	0	-0.42	1	1
RAC1	0.007	0.14	0.3	8	-0.48	26	34
B-cell antigen/BCR complex/LYN/SYK	-0.004	0.14	-10000	0	-0.49	26	26
CARD11	-0.014	0.14	0.26	7	-0.45	28	35
FCGR2B	0.002	0.11	-10000	0	-0.42	29	29
PPP3CA	0.027	0.061	-10000	0	-0.42	9	9
BCL10	0.034	0.008	-10000	0	-10000	0	0
IKK complex	0.024	0.05	0.16	21	-0.13	2	23
PTPRC	0.005	0.097	-10000	0	-0.42	24	24
PDPK1	0.004	0.085	0.2	33	-0.22	17	50
PPP3CB	0.035	0.021	-10000	0	-0.42	1	1
PPP3CC	0.024	0.043	-10000	0	-0.42	4	4
POU2F2	0.025	0.032	0.13	5	-10000	0	5

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0.031	0.023	-10000	0	-0.42	1	1
MKNK1	0.035	0.006	-10000	0	-10000	0	0
mol:PIP3	-0.024	0.1	0.26	5	-0.27	63	68
FRAP1	-0.009	0.12	-10000	0	-0.45	24	24
AKT1	-0.024	0.096	0.17	25	-0.25	57	82
INSR	0.033	0.029	-10000	0	-0.42	2	2
Insulin Receptor/Insulin	0.044	0.026	-10000	0	-0.25	3	3
mol:GTP	0.011	0.096	0.33	1	-0.22	42	43
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.006	0.051	-10000	0	-0.2	17	17
TSC2	0.031	0.023	-10000	0	-0.42	1	1
RHEB/GDP	0.004	0.081	-10000	0	-0.27	12	12
TSC1	0.036	0.005	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.009	0.11	-10000	0	-0.3	64	64
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.011	0.068	-10000	0	-0.24	13	13
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0	0.093	0.24	4	-0.34	17	21
MAP3K5	-0.013	0.084	0.19	8	-0.25	48	56
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
apoptosis	-0.013	0.084	0.19	8	-0.25	48	56
mol:LY294002	0	0	0.001	2	-0.001	58	60
EIF4B	-0.001	0.085	0.23	4	-0.3	18	22
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.012	0.083	0.22	4	-0.28	16	20
eIF4E/eIF4G1/eIF4A1	0.001	0.077	-10000	0	-0.32	15	15
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.002	0.12	-10000	0	-0.27	74	74
mTOR/RHEB/GTP/Raptor/GBL	0.01	0.061	0.22	3	-0.23	9	12
FKBP1A	0.035	0.008	-10000	0	-10000	0	0
RHEB/GTP	0.019	0.09	0.31	1	-0.28	11	12
mol:Amino Acids	0	0	0.001	2	-0.001	58	60
FKBP12/Rapamycin	0.026	0.006	-10000	0	-10000	0	0
PDPK1	-0.033	0.094	0.17	22	-0.26	57	79
EIF4E	0.035	0.005	-10000	0	-10000	0	0
ASK1/PP5C	-0.032	0.21	-10000	0	-0.58	57	57
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.017	0.052	-10000	0	-0.34	2	2
TSC1/TSC2	0.013	0.1	0.36	1	-0.3	15	16
tumor necrosis factor receptor activity	0	0	0.001	58	-0.001	2	60
RPS6	0.034	0.022	-10000	0	-0.42	1	1
PPP5C	0.031	0.041	-10000	0	-0.42	4	4
EIF4G1	0.031	0.041	-10000	0	-0.42	4	4
IRS1	-0.031	0.11	-10000	0	-0.32	64	64
INS	0.034	0.021	-10000	0	-0.42	1	1
PTEN	0.026	0.06	-10000	0	-0.42	9	9
PDK2	-0.032	0.1	0.17	27	-0.26	61	88
EIF4EBP1	-0.067	0.31	-10000	0	-1.1	38	38
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
PPP2R5D	-0.006	0.11	-10000	0	-0.41	23	23
peptide biosynthetic process	0.017	0.03	0.19	5	-0.23	5	10
RHEB	0.035	0.007	-10000	0	-10000	0	0
EIF4A1	0.032	0.012	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.004	19	-0.003	7	26
EEF2	0.017	0.03	0.19	5	-0.23	5	10
eIF4E/4E-BP1	-0.047	0.3	-10000	0	-1.1	38	38

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.004	0.11	-10000	0	-0.44	29	29
PDGF/PDGFRA/CRKL	0.019	0.088	-10000	0	-0.3	32	32
positive regulation of JUN kinase activity	0.047	0.073	-10000	0	-0.23	22	22
CRKL	0.03	0.041	-10000	0	-0.42	4	4
PDGF/PDGFRA/Caveolin-3	0.021	0.086	-10000	0	-0.3	30	30
AP1	-0.14	0.3	-10000	0	-0.81	76	76
mol:IP3	-0.014	0.079	-10000	0	-0.33	26	26
PLCG1	-0.014	0.079	-10000	0	-0.33	26	26
PDGF/PDGFRA/alphaV Integrin	0.013	0.11	-10000	0	-0.32	43	43
RAPGEF1	0.036	0.004	-10000	0	-10000	0	0
CRK	0.031	0.023	-10000	0	-0.42	1	1
mol:Ca2+	-0.014	0.079	-10000	0	-0.33	26	26
CAV3	0.034	0.022	-10000	0	-0.42	1	1
CAV1	0.028	0.05	-10000	0	-0.42	6	6
SHC/Grb2/SOS1	0.049	0.074	-10000	0	-0.23	22	22
PDGF/PDGFRA/Shf	0.021	0.086	-10000	0	-0.3	30	30
FOS	-0.14	0.29	0.31	2	-0.8	76	78
JUN	-0.051	0.081	-10000	0	-0.34	34	34
oligodendrocyte development	0.012	0.11	-10000	0	-0.32	43	43
GRB2	0.033	0.01	-10000	0	-10000	0	0
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
mol:DAG	-0.014	0.079	-10000	0	-0.33	26	26
PDGF/PDGFRA	-0.004	0.11	-10000	0	-0.44	29	29
actin cytoskeleton reorganization	0.019	0.09	-10000	0	-0.3	33	33
SRF	0.017	0.012	-10000	0	-10000	0	0
SHC1	0.027	0.025	-10000	0	-0.42	1	1
PI3K	0.034	0.1	-10000	0	-0.29	41	41
PDGF/PDGFRA/Crk/C3G	0.044	0.079	-10000	0	-0.26	30	30
JAK1	-0.01	0.079	-10000	0	-0.31	30	30
ELK1/SRF	-0.026	0.071	0.15	19	-0.26	29	48
SHB	0.03	0.046	-10000	0	-0.42	5	5
SHF	0.033	0.022	-10000	0	-0.42	1	1
CSNK2A1	0.039	0.022	-10000	0	-10000	0	0
GO:0007205	-0.023	0.083	-10000	0	-0.36	27	27
SOS1	0.034	0.021	-10000	0	-0.42	1	1
Ras protein signal transduction	0.047	0.073	-10000	0	-0.23	22	22
PDGF/PDGFRA/SHB	0.019	0.09	-10000	0	-0.3	33	33
PDGF/PDGFRA/Caveolin-1	0.017	0.095	-10000	0	-0.32	33	33
ITGAV	0.021	0.08	-10000	0	-0.42	16	16
ELK1	-0.035	0.079	0.22	3	-0.32	29	32
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
PDGF/PDGFRA/Crk	0.019	0.086	-10000	0	-0.3	30	30
JAK-STAT cascade	-0.01	0.079	-10000	0	-0.31	30	30
cell proliferation	0.021	0.086	-10000	0	-0.3	30	30

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.029	0.23	-10000	0	-0.98	28	28
regulation of axonogenesis	0	0.058	0.3	12	-10000	0	12
myoblast fusion	-0.006	0.11	0.4	31	-10000	0	31
mol:GTP	0.01	0.066	-10000	0	-0.23	32	32
regulation of calcium-dependent cell-cell adhesion	-0.047	0.082	0.24	33	-10000	0	33
ARF1/GTP	0.024	0.056	-10000	0	-0.19	22	22
mol:GM1	0	0.047	-10000	0	-0.18	27	27
mol:Choline	-0.002	0.058	-10000	0	-0.27	16	16
lamellipodium assembly	-0.006	0.12	-10000	0	-0.45	34	34
MAPK3	0.008	0.085	-10000	0	-0.33	29	29
ARF6/GTP/NME1/Tiam1	0.048	0.082	-10000	0	-0.24	33	33
ARF1	0.027	0.025	-10000	0	-0.42	1	1
ARF6/GDP	0.006	0.11	-10000	0	-0.4	31	31
ARF1/GDP	0.008	0.1	-10000	0	-0.36	29	29
ARF6	0.031	0.056	-10000	0	-0.32	5	5
RAB11A	0.034	0.021	-10000	0	-0.42	1	1
TIAM1	0.025	0.06	-10000	0	-0.43	8	8
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.009	0.086	-10000	0	-0.34	28	28
actin filament bundle formation	-0.016	0.11	0.37	34	-10000	0	34
KALRN	0.001	0.082	-10000	0	-0.31	31	31
RAB11FIP3/RAB11A	0.047	0.043	-10000	0	-0.3	7	7
RhoA/GDP	0.016	0.11	-10000	0	-0.38	34	34
NME1	0.03	0.02	-10000	0	-10000	0	0
Rac1/GDP	0.022	0.11	-10000	0	-0.37	33	33
substrate adhesion-dependent cell spreading	0.01	0.066	-10000	0	-0.23	32	32
cortical actin cytoskeleton organization	-0.006	0.13	-10000	0	-0.46	34	34
RAC1	0.035	0.006	-10000	0	-10000	0	0
liver development	0.01	0.066	-10000	0	-0.23	32	32
ARF6/GTP	0.01	0.066	-10000	0	-0.23	32	32
RhoA/GTP	0.025	0.071	-10000	0	-0.21	35	35
mol:GDP	-0.008	0.1	-10000	0	-0.39	31	31
ARF6/GTP/RAB11FIP3/RAB11A	0.047	0.067	-10000	0	-0.18	31	31
RHOA	0.026	0.061	-10000	0	-0.42	9	9
PLD1	0.007	0.067	-10000	0	-0.23	30	30
RAB11FIP3	0.031	0.05	-10000	0	-0.42	6	6
tube morphogenesis	-0.006	0.12	-10000	0	-0.45	34	34
ruffle organization	0	0.058	-10000	0	-0.3	12	12
regulation of epithelial cell migration	0.01	0.066	-10000	0	-0.23	32	32
PLD2	0.01	0.054	-10000	0	-0.2	25	25
PIP5K1A	0	0.058	-10000	0	-0.3	12	12
mol:Phosphatidic acid	-0.002	0.058	-10000	0	-0.27	16	16
Rac1/GTP	-0.006	0.13	-10000	0	-0.46	34	34

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.03	0.24	-10000	0	-0.75	24	24
PCK1	0.018	0.17	-10000	0	-0.99	5	5
HNF4A	-0.006	0.26	0.56	7	-0.77	22	29
KCNJ11	-0.053	0.34	-10000	0	-0.98	45	45
AKT1	-0.002	0.17	-10000	0	-0.42	23	23
response to starvation	0.004	0.002	-10000	0	-10000	0	0
DLK1	-0.021	0.27	0.63	1	-0.8	22	23
NKX2-1	0.039	0.13	0.35	5	-0.35	7	12
ACADM	-0.031	0.26	-10000	0	-0.77	28	28
TAT	-0.005	0.16	-10000	0	-0.58	7	7
CEBPB	0.03	0.051	-10000	0	-0.42	6	6
CEBPA	0.029	0.07	-10000	0	-0.42	12	12
TTR	-0.026	0.28	0.57	1	-0.71	43	44
PKLR	0.014	0.25	0.56	1	-0.72	22	23
APOA1	-0.025	0.28	-10000	0	-0.88	22	22
CPT1C	-0.028	0.27	0.56	1	-0.8	31	32
ALAS1	0.011	0.18	-10000	0	-1.1	4	4
TFRC	-0.039	0.35	-10000	0	-1.2	36	36
FOXF1	0.026	0.032	-10000	0	-0.42	2	2
NF1	0.036	0.035	-10000	0	-0.36	3	3
HNF1A (dimer)	0.008	0.02	-10000	0	-0.21	4	4
CPT1A	-0.022	0.27	0.56	3	-0.84	27	30
HMGCS1	-0.02	0.24	-10000	0	-0.74	24	24
NR3C1	0.032	0.079	-10000	0	-0.4	16	16
CPT1B	-0.022	0.24	-10000	0	-0.75	22	22
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.035	0.021	-10000	0	-0.42	1	1
GCK	-0.024	0.25	-10000	0	-0.76	24	24
CREB1	0.041	0.029	-10000	0	-0.24	4	4
IGFBP1	0.01	0.14	-10000	0	-1.3	1	1
PDX1	0.007	0.15	-10000	0	-0.37	24	24
UCP2	-0.05	0.31	0.56	2	-0.85	47	49
ALDOB	-0.022	0.27	-10000	0	-0.8	23	23
AFP	-0.024	0.12	-10000	0	-0.82	3	3
BDH1	-0.033	0.26	-10000	0	-0.77	31	31
HADH	-0.022	0.26	-10000	0	-0.62	52	52
F2	-0.008	0.29	-10000	0	-0.86	23	23
HNF1A	0.008	0.02	-10000	0	-0.21	4	4
G6PC	0.04	0.091	-10000	0	-1.3	1	1
SLC2A2	0.004	0.2	-10000	0	-0.95	6	6
INS	0.024	0.024	0.2	1	-0.43	1	2
FOXA1	-0.037	0.18	-10000	0	-0.4	97	97
FOXA3	0.043	0.076	-10000	0	-0.26	9	9
FOXA2	-0.009	0.32	-10000	0	-0.72	49	49
ABCC8	-0.2	0.48	-10000	0	-0.9	150	150
ALB	-0.03	0.15	-10000	0	-0.95	7	7

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	-0.001	0.047	0.2	23	-0.12	5	28
BUB1B	-0.018	0.097	0.12	2	-0.3	43	45
PLK1	0.004	0.034	0.092	12	-0.088	21	33
PLK1S1	0.002	0.019	0.053	14	-0.047	21	35
KIF2A	0.003	0.03	0.081	12	-0.079	21	33
regulation of mitotic centrosome separation	0.004	0.034	0.092	12	-0.087	21	33
GOLGA2	0.035	0.005	-10000	0	-10000	0	0
Hec1/SPC24	-0.008	0.019	-10000	0	-0.069	29	29
WEE1	-0.004	0.093	-10000	0	-0.36	24	24
cytokinesis	-0.023	0.14	-10000	0	-0.46	38	38
PP2A-alpha B56	-0.034	0.28	-10000	0	-0.71	70	70
AURKA	0.003	0.02	0.059	15	-0.049	15	30
PICH/PLK1	-0.019	0.095	-10000	0	-0.33	35	35
CENPE	-0.013	0.069	0.24	2	-0.25	32	34
RhoA/GTP	0.02	0.043	-10000	0	-0.3	9	9
positive regulation of microtubule depolymerization	0.003	0.03	0.081	12	-0.078	21	33
PPP2CA	0.031	0.046	-10000	0	-0.42	5	5
FZR1	0.035	0.006	-10000	0	-10000	0	0
TPX2	-0.008	0.08	0.12	2	-0.27	40	42
PAK1	0.014	0.087	-10000	0	-0.43	18	18
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	0.034	0.021	-10000	0	-0.42	1	1
CLSPN	0.003	0.058	-10000	0	-0.28	18	18
GORASP1	0.034	0.022	-10000	0	-0.42	1	1
metaphase	0.002	0.006	0.019	48	-10000	0	48
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.002	0.019	0.053	14	-0.047	21	35
G2 phase of mitotic cell cycle	-0.001	0.002	0.011	2	-10000	0	2
STAG2	0.036	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.008	0.11	-10000	0	-0.52	19	19
spindle elongation	0.004	0.034	0.092	12	-0.087	21	33
ODF2	0.036	0.005	-10000	0	-10000	0	0
BUB1	-0.073	0.29	-10000	0	-0.76	72	72
TPT1	-0.008	0.063	-10000	0	-0.19	49	49
CDC25C	-0.014	0.11	-10000	0	-0.36	42	42
CDC25B	0.027	0.045	-10000	0	-0.44	4	4
SGOL1	0.001	0.047	0.12	5	-0.2	23	28
RHOA	0.026	0.061	-10000	0	-0.42	9	9
CCNB1/CDK1	0.028	0.13	-10000	0	-0.37	41	41
CDC14B	0.005	0.024	-10000	0	-0.3	3	3
CDC20	0.016	0.087	-10000	0	-0.42	19	19
PLK1/PBIP1	-0.005	0.057	0.095	3	-0.21	28	31
mitosis	0	0.003	0.013	12	-10000	0	12
FBXO5	-0.002	0.05	0.13	9	-0.2	11	20
CDC2	0.013	0.097	-10000	0	-0.44	22	22
NDC80	0	0	-10000	0	-10000	0	0
metaphase plate congression	0.004	0.055	-10000	0	-0.25	21	21
ERCC6L	-0.013	0.11	-10000	0	-0.36	41	41
NLP/gamma Tubulin	0.007	0.028	0.075	14	-0.082	8	22
microtubule cytoskeleton organization	-0.008	0.063	-10000	0	-0.19	49	49
G2/M transition DNA damage checkpoint	0	0.003	0.011	22	-10000	0	22
PPP1R12A	0.035	0.021	-10000	0	-0.43	1	1
interphase	0	0.003	0.011	22	-10000	0	22
PLK1/PRC1-2	0.013	0.12	-10000	0	-0.33	43	43
GRASP65/GM130/RAB1/GTP/PLK1	0.049	0.049	-10000	0	-0.19	2	2
RAB1A	0.034	0.021	-10000	0	-0.42	1	1
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.003	0.025	0.069	16	-0.069	12	28
mitotic prometaphase	0	0.004	0.018	21	-10000	0	21
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.055	-10000	0	-0.35	4	4
microtubule-based process	0.006	0.078	0.12	2	-0.25	35	37
Golgi organization	0.004	0.034	0.092	12	-0.087	21	33
Cohesin/SA2	0.021	0.035	0.11	2	-0.12	1	3
PPP1CB/MYPT1	0.051	0.018	-10000	0	-0.31	1	1
KIF20A	0.003	0.12	-10000	0	-0.42	35	35
APC/C/CDC20	0.013	0.064	-10000	0	-0.25	20	20
PPP2R1A	0.035	0.007	-10000	0	-10000	0	0
chromosome segregation	-0.005	0.056	0.093	3	-0.21	28	31
PRC1	0.008	0.1	-10000	0	-0.42	28	28
ECT2	0.004	0.072	0.22	28	-0.22	17	45
C13orf34	0.003	0.028	0.074	16	-0.072	21	37
NUDC	0.004	0.055	-10000	0	-0.25	21	21
regulation of attachment of spindle microtubules to kinetochore	-0.018	0.096	0.12	2	-0.3	43	45
spindle assembly	0.01	0.036	0.09	22	-0.082	12	34
spindle stabilization	0.002	0.019	0.053	14	-0.047	21	35
APC/C/HCDH1	0.03	0.023	-10000	0	-0.25	3	3
MKLP2/PLK1	0.006	0.078	0.12	2	-0.25	35	37
CCNB1	0.011	0.1	-10000	0	-0.44	25	25
PPP1CB	0.036	0.005	-10000	0	-10000	0	0
BTRC	0.034	0.022	-10000	0	-0.42	1	1
ROCK2	0.006	0.064	0.21	1	-0.34	10	11
TUBG1	0.009	0.038	-10000	0	-0.17	14	14
G2/M transition of mitotic cell cycle	-0.021	0.11	-10000	0	-0.37	41	41
MLF1IP	-0.009	0.07	-10000	0	-0.3	27	27
INCENP	0.027	0.055	-10000	0	-0.43	7	7

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.019	0.073	-10000	0	-0.29	26	26
PDGFRB	0.028	0.058	-10000	0	-0.43	8	8
SPHK1	-0.034	0.2	-10000	0	-0.76	35	35
mol:S1P	-0.02	0.19	-10000	0	-0.65	35	35
S1P1/S1P/Gi	-0.02	0.16	-10000	0	-0.51	32	32
GNAO1	0.03	0.015	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/PLCgamma1	0.001	0.15	0.33	2	-0.48	25	27
PLCG1	-0.015	0.15	0.3	2	-0.49	28	30
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.028	0.058	-10000	0	-0.43	8	8
GNAI2	0.028	0.058	-10000	0	-0.42	8	8
GNAI3	0.036	0.008	-10000	0	-10000	0	0
GNAI1	0.018	0.086	-10000	0	-0.43	18	18
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.002	0.12	-10000	0	-0.52	25	25
S1P1/S1P	-0.011	0.17	0.25	2	-0.46	53	55
negative regulation of cAMP metabolic process	-0.018	0.16	-10000	0	-0.49	32	32
MAPK3	-0.012	0.16	0.32	11	-0.55	26	37
calcium-dependent phospholipase C activity	0	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.026	0.004	-10000	0	-10000	0	0
RhoA/GDP	0.02	0.043	-10000	0	-0.3	9	9
KDR	0.028	0.059	-10000	0	-0.21	23	23
PLCB2	-0.01	0.15	0.24	2	-0.42	48	50
RAC1	0.035	0.006	-10000	0	-10000	0	0
RhoA/GTP	-0.018	0.14	-10000	0	-0.38	55	55
receptor internalization	-0.01	0.16	0.24	2	-0.42	55	57
PTGS2	-0.012	0.17	-10000	0	-0.77	14	14
Rac1/GTP	-0.015	0.14	-10000	0	-0.39	50	50
RHOA	0.026	0.061	-10000	0	-0.42	9	9
VEGFA	-0.004	0.034	-10000	0	-0.15	26	26
negative regulation of T cell proliferation	-0.018	0.16	-10000	0	-0.49	32	32
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.024	0.068	-10000	0	-0.42	11	11
MAPK1	-0.02	0.15	-10000	0	-0.54	28	28
S1P1/S1P/PDGFB-D/PDGFRB	0.008	0.18	0.31	2	-0.45	50	52
ABCC1	0.029	0.042	-10000	0	-0.43	4	4

×

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

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
BAG4	0.027	0.025	-10000	0	-0.42	1	1
Caspase 8 (4 units)	0.03	0.13	-10000	0	-0.39	23	23
NEF	-0.012	0.049	-10000	0	-0.17	45	45
NFKBIA	0.021	0.05	-10000	0	-0.46	2	2
BIRC3	-0.015	0.14	-10000	0	-0.46	42	42
CYCS	-0.005	0.12	0.19	4	-0.33	38	42
RIPK1	0.035	0.007	-10000	0	-10000	0	0
CD247	-0.012	0.049	-10000	0	-0.17	45	45
MAP2K7	0.005	0.18	-10000	0	-0.74	17	17
protein ubiquitination	-0.015	0.12	0.22	1	-0.37	25	26
CRADD	0.029	0.054	-10000	0	-0.42	7	7
DAXX	0.035	0.005	-10000	0	-10000	0	0
FAS	0.008	0.1	-10000	0	-0.42	28	28
BID	-0.006	0.12	-10000	0	-0.3	57	57
NF-kappa-B/RelA/I kappa B alpha	0.04	0.1	-10000	0	-0.26	41	41
TRADD	0.029	0.014	-10000	0	-10000	0	0
MAP3K5	0.013	0.093	-10000	0	-0.42	22	22
CFLAR	0.031	0.046	-10000	0	-0.42	5	5
FADD	0.029	0.014	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.04	0.1	-10000	0	-0.26	41	41
MAPK8	0.004	0.16	0.42	1	-0.66	17	18
APAF1	0.032	0.041	-10000	0	-0.42	4	4
TRAF1	0.034	0.021	-10000	0	-0.42	1	1
TRAF2	0.033	0.029	-10000	0	-0.42	2	2
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.003	0.13	-10000	0	-0.31	52	52
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.016	0.14	-10000	0	-0.41	33	33
CHUK	-0.019	0.13	-10000	0	-0.4	25	25
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.055	0.094	-10000	0	-0.24	34	34
TCRz/NEF	-0.018	0.085	-10000	0	-0.29	45	45
TNF	0.026	0.061	-10000	0	-0.42	9	9
FASLG	-0.02	0.13	-10000	0	-0.52	34	34
NFKB1	0.022	0.042	-10000	0	-0.14	3	3
TNFR1A/BAG4/TNF-alpha	0.048	0.049	-10000	0	-0.25	7	7
CASP6	0.024	0.15	-10000	0	-0.55	21	21
CASP7	-0.043	0.2	0.29	1	-0.46	73	74
RELA	0.022	0.042	-10000	0	-0.14	3	3
CASP2	0.035	0.007	-10000	0	-10000	0	0
CASP3	-0.041	0.19	-10000	0	-0.46	68	68
TNFRSF1A	0.033	0.022	-10000	0	-0.42	1	1
TNFR1A/BAG4	0.038	0.028	-10000	0	-0.3	1	1
CASP8	0.036	0.004	-10000	0	-10000	0	0
CASP9	0.034	0.022	-10000	0	-0.42	1	1
MAP3K14	-0.014	0.14	0.24	2	-0.41	29	31
APAF-1/Caspase 9	-0.014	0.14	0.2	1	-0.34	55	56
BCL2	-0.031	0.16	0.58	1	-0.54	22	23

×

Visual signal transduction: Cones

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.046	0.056	-10000	0	-0.23	17	17
RGS9BP	-0.022	0.15	-10000	0	-0.42	60	60
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0	0	-10000	0	-10000	0	0
mol:Na +	0.023	0.062	-10000	0	-0.26	20	20
mol:ADP	0.007	0.019	-10000	0	-0.3	2	2
GNAT2	0.018	0.087	-10000	0	-0.42	19	19
RGS9-1/Gbeta5/R9AP	0.007	0.12	-10000	0	-0.27	72	72
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.025	0.077	-10000	0	-0.27	31	31
GRK7	0.033	0.029	-10000	0	-0.42	2	2
CNGB3	0.022	0.051	-10000	0	-0.42	6	6
Cone Metarhodopsin II/X-Arrestin	0.027	0.001	-10000	0	-10000	0	0
mol:Ca2+	0.039	0.09	0.19	93	-0.24	21	114
Cone PDE6	0.021	0.13	-10000	0	-0.25	83	83
Cone Metarhodopsin II	0.022	0.016	-10000	0	-0.22	2	2
Na + (4 Units)	0.037	0.065	-10000	0	-0.24	21	21
GNAT2/GDP	0.011	0.12	-10000	0	-0.24	85	85
GNB5	0.024	0.067	-10000	0	-0.42	11	11
mol:GMP (4 units)	0.004	0.079	0.19	16	-0.26	35	51
Cone Transducin	0.05	0.06	-10000	0	-0.24	17	17
SLC24A2	0.032	0.036	-10000	0	-0.42	3	3
GNB3/GNGT2	0.047	0.022	-10000	0	-0.3	1	1
GNB3	0.034	0.009	-10000	0	-10000	0	0
GNAT2/GTP	0.014	0.062	-10000	0	-0.3	19	19
CNGA3	0.017	0.08	-10000	0	-0.42	16	16
ARR3	0.036	0.002	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.023	0.062	-10000	0	-0.26	20	20
mol:Pi	0.007	0.12	-10000	0	-0.27	72	72
Cone CNG Channel	0.032	0.1	-10000	0	-0.26	45	45
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.032	0.036	-10000	0	-0.42	3	3
RGS9	0.017	0.067	-10000	0	-0.42	11	11
PDE6C	0.03	0.05	-10000	0	-0.42	6	6
GNGT2	0.033	0.03	-10000	0	-0.42	2	2
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.021	0.075	-10000	0	-0.42	14	14

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.04	0.11	-10000	0	-0.46	19	19
HDAC1	0.04	0.028	-10000	0	-0.43	1	1
AES	0.037	0.008	-10000	0	-10000	0	0
FBXW11	0.034	0.021	-10000	0	-0.42	1	1
DTX1	0.032	0.036	-10000	0	-0.42	3	3
LRP6/FZD1	0.041	0.053	-10000	0	-0.3	11	11
TLE1	0.006	0.11	-10000	0	-0.42	33	33
AP1	-0.026	0.11	-10000	0	-0.26	79	79
NCSTN	0.028	0.025	-10000	0	-0.42	1	1
ADAM10	0.033	0.03	-10000	0	-0.42	2	2
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.037	0.15	-10000	0	-0.68	8	8
NICD/RBPSUH	0.004	0.098	-10000	0	-0.45	19	19
WIF1	0.029	0.014	-10000	0	-10000	0	0
NOTCH1	0.013	0.1	-10000	0	-0.48	19	19
PSENEN	0.035	0.006	-10000	0	-10000	0	0
KREMEN2	-0.091	0.19	-10000	0	-0.42	129	129
DKK1	-0.028	0.15	-10000	0	-0.42	61	61
beta catenin/beta TrCP1	0.013	0.099	0.28	1	-0.37	12	13
APH1B	0.023	0.073	-10000	0	-0.42	13	13
APH1A	0.031	0.036	-10000	0	-0.42	3	3
AXIN1	0.015	0.051	-10000	0	-0.47	1	1
CtBP/CBP/TCF1/TLE1/AES	0.025	0.089	0.29	3	-0.24	26	29
PSEN1	0.032	0.036	-10000	0	-0.42	3	3
FOS	-0.031	0.15	-10000	0	-0.42	66	66
JUN	-0.001	0.12	-10000	0	-0.42	39	39
MAP3K7	0.035	0.013	-10000	0	-10000	0	0
CTNNB1	-0.003	0.096	0.26	2	-0.39	12	14
MAPK3	0.032	0.023	-10000	0	-0.42	1	1
DKK2/LRP6/Kremen 2	-0.045	0.15	-10000	0	-0.26	153	153
HNF1A	0.002	0.006	-10000	0	-10000	0	0
CTBP1	0.036	0.01	-10000	0	-10000	0	0
MYC	-0.083	0.34	-10000	0	-1.3	35	35
NKD1	0.027	0.038	-10000	0	-0.42	3	3
FZD1	0.028	0.054	-10000	0	-0.42	7	7
NOTCH1 precursor/Deltex homolog 1	0.041	0.11	-10000	0	-0.46	19	19
apoptosis	-0.026	0.11	-10000	0	-0.26	79	79
Delta 1/NOTCHprecursor	0.039	0.11	-10000	0	-0.45	19	19
DLL1	0.033	0.01	-10000	0	-10000	0	0
PPARD	0.006	0.1	-10000	0	-0.84	6	6
Gamma Secretase	0.067	0.07	-10000	0	-0.23	14	14
APC	-0.001	0.1	0.26	1	-0.45	18	19
DVL1	0.024	0.028	-10000	0	-0.26	2	2
CSNK2A1	0.034	0.008	-10000	0	-10000	0	0
MAP3K7IP1	0.036	0.012	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.062	0.16	-10000	0	-0.28	169	169
LRP6	0.029	0.046	-10000	0	-0.42	5	5
CSNK1A1	0.035	0.006	-10000	0	-10000	0	0
NLK	0.029	0.024	-10000	0	-0.24	1	1
CCND1	-0.2	0.5	-10000	0	-1.3	84	84
WNT1	0.034	0.021	-10000	0	-0.42	1	1
Axin1/APC/beta catenin	0.023	0.099	0.34	2	-0.48	7	9
DKK2	0.006	0.11	-10000	0	-0.42	31	31
NOTCH1 precursor/DVL1	0.037	0.1	-10000	0	-0.55	9	9
GSK3B	0.036	0.005	-10000	0	-10000	0	0
FRAT1	0.03	0.054	-10000	0	-0.42	7	7
NOTCH/Deltex homolog 1	0.041	0.11	-10000	0	-0.47	19	19
PPP2R5D	0.011	0.068	0.25	2	-0.32	17	19
MAPK1	0.033	0.022	-10000	0	-0.42	1	1
WNT1/LRP6/FZD1	0.07	0.056	-10000	0	-0.24	12	12
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.026	0.02	-10000	0	-10000	0	0

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.019	0.1	-10000	0	-0.27	53	53
fibroblast growth factor receptor signaling pathway	0.018	0.1	-10000	0	-0.27	53	53
LAMA1	0.034	0.009	-10000	0	-10000	0	0
PRNP	0.028	0.054	-10000	0	-0.42	7	7
GPC1/SLIT2	0.013	0.11	-10000	0	-0.31	51	51
SMAD2	0.004	0.064	0.19	5	-0.24	29	34
GPC1/PrPc/Cu2+	0.029	0.068	-10000	0	-0.26	25	25
GPC1/Laminin alpha1	0.035	0.068	-10000	0	-0.3	19	19
TDGF1	0.034	0.008	-10000	0	-10000	0	0
CRIPTO/GPC1	0.036	0.068	-10000	0	-0.3	19	19
APP/GPC1	0.016	0.1	-10000	0	-0.31	46	46
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.005	0.06	-10000	0	-0.26	25	25
FLT1	0.026	0.054	-10000	0	-0.42	7	7
GPC1/TGFB/TGFBR1/TGFBR2	0.049	0.081	-10000	0	-0.26	30	30
SERPINC1	0.027	0.025	-10000	0	-0.42	1	1
FYN	0.005	0.057	-10000	0	-0.26	23	23
FGR	0.008	0.053	-10000	0	-0.26	19	19
positive regulation of MAPKKK cascade	-0.023	0.12	0.28	1	-0.35	43	44
SLIT2	0.003	0.11	-10000	0	-0.42	34	34
GPC1/NRG	0.028	0.068	-10000	0	-0.3	19	19
NRG1	0.028	0.015	-10000	0	-10000	0	0
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.028	0.069	-10000	0	-0.26	25	25
LYN	0.009	0.045	-10000	0	-0.26	14	14
mol:Spermine	-0.003	0.058	-10000	0	-0.3	19	19
cell growth	0.018	0.1	-10000	0	-0.27	53	53
BMP signaling pathway	-0.017	0.087	0.42	19	-10000	0	19
SRC	0.007	0.056	-10000	0	-0.27	19	19
TGFBR1	0.027	0.061	-10000	0	-0.42	9	9
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	0.014	0.078	-10000	0	-0.42	15	15
GPC1	0.017	0.087	-10000	0	-0.42	19	19
TGFBR1 (dimer)	0.027	0.061	-10000	0	-0.42	9	9
VEGFA	0	0	-10000	0	-10000	0	0
BLK	0.006	0.046	-10000	0	-0.25	15	15
HCK	-0.001	0.07	-10000	0	-0.26	35	35
FGF2	-0.001	0.11	-10000	0	-0.42	34	34
FGFR1	0.021	0.061	-10000	0	-0.42	9	9
VEGFR1 homodimer	0.026	0.054	-10000	0	-0.42	7	7
TGFBR2	0.032	0.036	-10000	0	-0.42	3	3
cell death	0.016	0.1	-10000	0	-0.31	46	46
ATIII/GPC1	0.029	0.066	-10000	0	-0.3	17	17
PLA2G2A/GPC1	0.022	0.089	-10000	0	-0.31	33	33
LCK	-0.021	0.097	-10000	0	-0.26	71	71
neuron differentiation	0.028	0.068	-10000	0	-0.3	19	19
PrPc/Cu2+	0.021	0.038	-10000	0	-0.3	7	7
APP	0.008	0.1	-10000	0	-0.42	28	28
TGFBR2 (dimer)	0.032	0.036	-10000	0	-0.42	3	3

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.044	0.086	-10000	0	-0.22	38	38
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.03	0.041	-10000	0	-0.42	4	4
STAT1 (dimer)/Cbp/p300	0.033	0.099	0.31	1	-0.32	16	17
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.051	0.051	-10000	0	-0.26	4	4
antigen processing and presentation of peptide antigen via MHC class I	-0.017	0.094	-10000	0	-0.25	46	46
CaM/Ca2+	0.047	0.085	-10000	0	-0.21	38	38
RAP1A	0.03	0.05	-10000	0	-0.42	6	6
STAT1 (dimer)/SHP2	0.017	0.094	0.28	3	-0.24	46	49
AKT1	-0.012	0.094	0.28	11	-0.32	8	19
MAP2K1	-0.026	0.079	0.26	2	-0.28	13	15
MAP3K11	0.005	0.078	0.26	5	-0.21	38	43
IFNGR1	0.03	0.021	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.006	0.13	-10000	0	-0.45	18	18
Rap1/GTP	0.001	0.067	-10000	0	-0.21	31	31
CRKL/C3G	0.047	0.034	-10000	0	-0.3	4	4
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.058	0.092	-10000	0	-0.22	38	38
CEBPB	-0.016	0.16	0.34	2	-0.51	31	33
STAT3	0.028	0.031	-10000	0	-0.42	2	2
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.053	0.13	-10000	0	-0.84	6	6
STAT1	-0.003	0.089	0.29	3	-0.24	42	45
CALM1	0.035	0.007	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.007	0.12	-10000	0	-0.42	38	38
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
STAT1 (dimer)/PIAS1	0.017	0.092	0.29	3	-0.31	13	16
CEBPB/PTGES2/Cbp/p300	0.004	0.11	-10000	0	-0.33	31	31
mol:Ca2+	0.041	0.083	-10000	0	-0.22	38	38
MAPK3	-0.016	0.14	0.36	1	-0.63	13	14
STAT1 (dimer)	-0.012	0.14	-10000	0	-0.35	46	46
MAPK1	-0.044	0.21	0.4	1	-0.74	32	33
JAK2	0.028	0.036	-10000	0	-0.43	2	2
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
JAK1	0.028	0.04	-10000	0	-0.42	3	3
CAMK2D	0.023	0.073	-10000	0	-0.42	13	13
DAPK1	-0.007	0.13	0.3	2	-0.48	22	24
SMAD7	-0.002	0.059	0.16	8	-0.18	13	21
CBL/CRKL/C3G	0.033	0.083	0.3	2	-0.21	31	33
PI3K	0.035	0.096	-10000	0	-0.23	42	42
IFNG	-0.007	0.12	-10000	0	-0.43	38	38
apoptosis	-0.059	0.18	0.31	1	-0.42	84	85
CAMK2G	0.036	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	0.028	0.031	-10000	0	-0.42	2	2
CAMK2A	0.034	0.021	-10000	0	-0.42	1	1
CAMK2B	-0.014	0.13	-10000	0	-0.42	49	49
FRAP1	-0.019	0.085	0.28	8	-0.32	6	14
PRKCD	-0.013	0.092	0.29	10	-0.34	6	16
RAP1B	0.032	0.03	-10000	0	-0.42	2	2
negative regulation of cell growth	-0.017	0.094	-10000	0	-0.25	46	46
PTPN2	0.034	0.008	-10000	0	-10000	0	0
EP300	0.033	0.022	-10000	0	-0.42	1	1
IRF1	-0.006	0.11	0.32	7	-0.41	16	23
STAT1 (dimer)/PIASy	0.012	0.093	0.29	3	-0.27	21	24
SOCS1	0.018	0.12	-10000	0	-1.1	6	6
mol:GDP	0.03	0.079	0.28	2	-0.2	32	34
CASP1	-0.014	0.083	0.16	7	-0.25	41	48
PTGES2	0.035	0.005	-10000	0	-10000	0	0
IRF9	0	0.049	0.12	2	-0.15	18	20
mol:PI-3-4-5-P3	0.02	0.087	-10000	0	-0.22	43	43
RAP1/GDP	0.024	0.08	-10000	0	-0.25	15	15
CBL	0.003	0.073	0.29	2	-0.21	36	38
MAP3K1	-0.006	0.088	0.25	4	-0.22	52	56
PIAS1	0.035	0.006	-10000	0	-10000	0	0
PIAS4	0.032	0.036	-10000	0	-0.42	3	3
antigen processing and presentation of peptide antigen via MHC class II	-0.017	0.094	-10000	0	-0.25	46	46
PTPN11	0.007	0.079	0.29	4	-0.22	38	42
CREBBP	0.033	0.011	-10000	0	-10000	0	0
RAPGEF1	0.036	0.004	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.007	0.052	-10000	0	-0.3	14	14
MAP4K4	-0.026	0.11	0.22	1	-0.32	36	37
BAG4	0.027	0.025	-10000	0	-0.42	1	1
PKC zeta/ceramide	-0.008	0.048	0.12	2	-0.22	14	16
NFKBIA	0.033	0.03	-10000	0	-0.42	2	2
BIRC3	-0.01	0.12	-10000	0	-0.42	42	42
BAX	0.011	0.034	-10000	0	-0.37	2	2
RIPK1	0.035	0.007	-10000	0	-10000	0	0
AKT1	0.002	0.089	0.66	8	-0.39	3	11
BAD	-0.011	0.05	0.19	3	-0.23	12	15
SMPD1	0.006	0.065	0.2	2	-0.23	17	19
RB1	-0.016	0.056	-10000	0	-0.23	21	21
FADD/Caspase 8	0.009	0.12	0.28	6	-0.33	23	29
MAP2K4	-0.023	0.064	0.18	1	-0.22	35	36
NSMAF	0.026	0.047	-10000	0	-0.42	5	5
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.01	0.054	0.19	8	-0.24	10	18
EGF	-0.069	0.19	-10000	0	-0.42	110	110
mol:ceramide	-0.008	0.052	0.13	9	-0.23	14	23
MADD	0.035	0.005	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.005	0.075	-10000	0	-0.31	28	28
ASAH1	0.008	0.089	-10000	0	-0.42	20	20
negative regulation of cell cycle	-0.015	0.056	0.16	1	-0.23	21	22
cell proliferation	-0.013	0.092	0.24	1	-0.22	31	32
BID	-0.015	0.14	-10000	0	-0.65	15	15
MAP3K1	-0.021	0.066	-10000	0	-0.23	36	36
EIF2A	-0.014	0.065	0.19	14	-0.22	24	38
TRADD	0.029	0.014	-10000	0	-10000	0	0
CRADD	0.029	0.054	-10000	0	-0.42	7	7
MAPK3	-0.007	0.053	0.2	3	-0.23	10	13
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.012	0.061	0.2	3	-0.26	10	13
Cathepsin D/ceramide	0.006	0.06	0.15	1	-0.22	18	19
FADD	0.004	0.12	0.22	53	-0.33	23	76
KSR1	-0.009	0.051	0.19	3	-0.23	12	15
MAPK8	-0.013	0.059	-10000	0	-0.21	21	21
PRKRA	-0.009	0.052	0.19	4	-0.23	12	16
PDGFA	0.022	0.078	-10000	0	-0.42	15	15
TRAF2	0.033	0.029	-10000	0	-0.42	2	2
IGF1	-0.041	0.17	-10000	0	-0.42	80	80
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.008	0.051	0.13	9	-0.23	14	23
CTSD	0.029	0.046	-10000	0	-0.42	5	5
regulation of nitric oxide biosynthetic process	0.051	0.012	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.013	0.098	0.25	1	-0.24	31	32
PRKCD	0.032	0.03	-10000	0	-0.42	2	2
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.005	0.075	-10000	0	-0.31	28	28
RelA/NF kappa B1	0.051	0.012	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.024	0.073	-10000	0	-0.42	13	13
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.015	0.11	-10000	0	-0.36	28	28
TNFR1A/BAG4/TNF-alpha	0.048	0.049	-10000	0	-0.25	7	7
mol:Sphingosine-1-phosphate	0.007	0.052	-10000	0	-0.3	14	14
MAP2K1	-0.011	0.053	0.19	5	-0.23	9	14
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.035	0.006	-10000	0	-10000	0	0
CYCS	0.032	0.069	0.16	64	-0.18	3	67
TNFRSF1A	0.033	0.022	-10000	0	-0.42	1	1
NFKB1	0.035	0.005	-10000	0	-10000	0	0
TNFR1A/BAG4	0.038	0.028	-10000	0	-0.3	1	1
EIF2AK2	-0.017	0.062	0.18	6	-0.22	25	31
TNF-alpha/TNFR1A/FAN	0.05	0.052	-10000	0	-0.26	9	9
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.008	0.091	-10000	0	-0.36	16	16
MAP2K2	-0.012	0.054	0.2	3	-0.23	9	12
SMPD3	-0.027	0.13	0.19	1	-0.3	76	77
TNF	0.026	0.061	-10000	0	-0.42	9	9
PKC zeta/PAR4	0.018	0.051	-10000	0	-0.3	13	13
mol:PHOSPHOCHOLINE	0.037	0.094	0.2	103	-0.2	4	107
NF kappa B1/RelA/I kappa B alpha	0.068	0.057	-10000	0	-0.22	15	15
AIFM1	0.027	0.067	0.16	64	-0.16	8	72
BCL2	-0.057	0.18	-10000	0	-0.42	99	99

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.007	0.13	-10000	0	-0.42	44	44
positive regulation of NF-kappaB transcription factor activity	0.01	0.096	-10000	0	-0.29	44	44
MAP2K4	-0.009	0.1	0.22	1	-0.35	27	28
IKBKB	0.029	0.014	-10000	0	-10000	0	0
TNFRSF10B	0.027	0.016	-10000	0	-10000	0	0
TNFRSF10A	0.023	0.047	-10000	0	-0.42	5	5
SMPD1	-0.006	0.072	-10000	0	-0.21	43	43
IKBKG	0.036	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.027	0.016	-10000	0	-10000	0	0
TRAIL/TRAILR2	0.009	0.099	-10000	0	-0.3	44	44
TRAIL/TRAILR3	0.008	0.097	-10000	0	-0.29	45	45
TRAIL/TRAILR1	0.007	0.1	-10000	0	-0.31	46	46
TRAIL/TRAILR4	0.01	0.096	-10000	0	-0.29	44	44
TRAIL/TRAILR1/DAP3/GTP	0.019	0.081	-10000	0	-0.24	36	36
IKK complex	0.014	0.092	-10000	0	-0.4	15	15
RIPK1	0.035	0.007	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.02	0.018	-10000	0	-0.3	1	1
MAPK3	-0.01	0.084	-10000	0	-0.3	39	39
MAP3K1	-0.008	0.11	-10000	0	-0.37	30	30
TRAILR4 (trimer)	0.027	0.016	-10000	0	-10000	0	0
TRADD	0.029	0.014	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.023	0.047	-10000	0	-0.42	5	5
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.015	0.089	-10000	0	-0.29	34	34
CFLAR	0.031	0.046	-10000	0	-0.42	5	5
MAPK1	-0.009	0.082	-10000	0	-0.3	37	37
TRAIL/TRAILR1/FADD/TRADD/RIP	0.034	0.089	-10000	0	-0.23	33	33
mol:ceramide	-0.006	0.071	-10000	0	-0.21	43	43
FADD	0.029	0.014	-10000	0	-10000	0	0
MAPK8	-0.023	0.11	0.2	1	-0.35	31	32
TRAF2	0.033	0.029	-10000	0	-0.42	2	2
TRAILR3 (trimer)	0.024	0.026	-10000	0	-0.42	1	1
CHUK	0.025	0.067	-10000	0	-0.42	11	11
TRAIL/TRAILR1/FADD	0.022	0.087	-10000	0	-0.27	34	34
DAP3	0.027	0.025	-10000	0	-0.42	1	1
CASP10	0.015	0.084	0.33	4	-0.29	18	22
JNK cascade	0.01	0.096	-10000	0	-0.29	44	44
TRAIL (trimer)	-0.007	0.13	-10000	0	-0.42	44	44
TNFRSF10C	0.024	0.026	-10000	0	-0.42	1	1
TRAIL/TRAILR1/DAP3/GTP/FADD	0.025	0.077	-10000	0	-0.23	28	28
TRAIL/TRAILR2/FADD	0.023	0.083	-10000	0	-0.26	33	33
cell death	-0.006	0.071	-10000	0	-0.21	43	43
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.014	0.087	-10000	0	-0.29	33	33
TRAILR2 (trimer)	0.027	0.016	-10000	0	-10000	0	0
CASP8	0.024	0.043	-10000	0	-0.66	1	1
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.035	0.086	-10000	0	-0.22	32	32

×

Calcium signaling in the CD4+ TCR pathway

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
NFATC1	0.007	0.055	-10000	0	-0.25	16	16
NFATC2	0.013	0.035	-10000	0	-0.27	3	3
NFATC3	0.015	0.026	-10000	0	-10000	0	0
CD40LG	-0.02	0.18	0.37	3	-0.45	50	53
PTGS2	-0.021	0.17	0.37	3	-0.45	44	47
JUNB	0.032	0.041	-10000	0	-0.42	4	4
CaM/Ca2+/Calcineurin A alpha-beta B1	0.021	0.025	-10000	0	-0.11	1	1
CaM/Ca2+	0.021	0.025	-10000	0	-0.11	1	1
CALM1	0.032	0.019	-10000	0	-10000	0	0
JUN	-0.003	0.12	-10000	0	-0.42	39	39
mol:Ca2+	-0.001	0.009	-10000	0	-0.084	1	1
Calcineurin A alpha-beta B1/FKBP12/FK506	0.022	0.01	-10000	0	-10000	0	0
FOSL1	0.035	0.007	-10000	0	-10000	0	0
CREM	0.034	0.008	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	0.016	0.12	-10000	0	-0.32	28	28
FOS	-0.033	0.15	-10000	0	-0.42	66	66
IFNG	-0.036	0.21	0.37	3	-0.52	56	59
AP-1/NFAT1-c-4	0.001	0.22	-10000	0	-0.5	53	53
FASLG	-0.032	0.2	0.37	3	-0.52	52	55
NFAT1-c-4/ICER1	0.027	0.082	0.28	2	-0.24	14	16
IL2RA	-0.03	0.2	0.37	3	-0.49	57	60
FKBP12/FK506	0.025	0.006	-10000	0	-10000	0	0
CSF2	-0.021	0.18	0.37	3	-0.45	51	54
JunB/Fra1/NFAT1-c-4	0.045	0.093	0.26	1	-0.28	9	10
IL4	-0.019	0.18	0.37	3	-0.44	54	57
IL2	0.008	0.14	-10000	0	-0.98	10	10
IL3	0.019	0.12	-10000	0	-0.69	12	12
FKBP1A	0.034	0.008	-10000	0	-10000	0	0
BATF3	0	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.033	0.017	-10000	0	-10000	0	0

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.012	0.11	-10000	0	-0.23	75	75
TC10/GTP	0.03	0.066	-10000	0	-0.21	31	31
Insulin Receptor/Insulin/IRS1/Shp2	0.053	0.11	-10000	0	-0.25	55	55
HRAS	0.032	0.036	-10000	0	-0.42	3	3
APS homodimer	0	0	-10000	0	-10000	0	0
GRB14	-0.063	0.18	-10000	0	-0.42	98	98
FOXO3	-0.015	0.022	-10000	0	-0.096	2	2
AKT1	-0.047	0.13	0.3	8	-0.37	17	25
INSR	0.037	0.031	-10000	0	-0.42	2	2
Insulin Receptor/Insulin	0.079	0.061	-10000	0	-0.31	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.022	0.075	-10000	0	-0.42	14	14
SORBS1	0.008	0.1	-10000	0	-0.42	28	28
CRK	0.031	0.023	-10000	0	-0.42	1	1
PTPN1	0.004	0.037	-10000	0	-0.3	5	5
CAV1	-0.008	0.083	0.18	5	-0.23	58	63
CBL/APS/CAP/Crk-II/C3G	0.052	0.074	-10000	0	-0.22	29	29
Insulin Receptor/Insulin/IRS1/NCK2	0.054	0.11	-10000	0	-0.25	54	54
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.027	0.1	-10000	0	-0.22	67	67
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.018	0.081	-10000	0	-0.42	6	6
RPS6KB1	-0.041	0.11	0.28	7	-0.34	16	23
PARD6A	0.023	0.055	-10000	0	-0.42	7	7
CBL	0.031	0.012	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.007	0.11	-10000	0	-0.67	12	12
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.006	0.13	0.28	3	-0.34	18	21
HRAS/GTP	-0.001	0.063	-10000	0	-0.2	40	40
Insulin Receptor	0.037	0.031	-10000	0	-0.42	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.048	0.1	-10000	0	-0.23	42	42
PRKCI	0.003	0.11	-10000	0	-0.47	23	23
Insulin Receptor/Insulin/GRB14/PDK1	-0.037	0.12	-10000	0	-0.23	136	136
SHC1	0.027	0.025	-10000	0	-0.42	1	1
negative regulation of MAPKKK cascade	0.044	0.11	-10000	0	-0.58	13	13
PI3K	0.039	0.11	-10000	0	-0.23	67	67
NCK2	0.036	0.004	-10000	0	-10000	0	0
RHOQ	0.033	0.035	-10000	0	-0.42	3	3
mol:H2O2	0	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.024	0.025	-10000	0	-0.3	3	3
AKT2	-0.048	0.13	0.3	8	-0.36	17	25
PRKCZ	-0.008	0.082	-10000	0	-0.41	16	16
SH2B2	0	0	-10000	0	-10000	0	0
SHC/SHIP	-0.002	0.07	0.17	3	-0.22	44	47
F2RL2	-0.018	0.14	-10000	0	-0.42	56	56
TRIP10	0.032	0.041	-10000	0	-0.42	4	4
Insulin Receptor/Insulin/Shc	0.053	0.041	-10000	0	-0.22	3	3
TC10/GTP/CIP4/Exocyst	0.043	0.036	-10000	0	-0.25	7	7
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.074	0.06	-10000	0	-0.22	4	4
RAPGEF1	0.036	0.004	-10000	0	-10000	0	0
RASA1	0.028	0.054	-10000	0	-0.42	7	7
NCK1	0.034	0.022	-10000	0	-0.42	1	1
CBL/APS/CAP/Crk-II	0.039	0.071	-10000	0	-0.23	29	29
TC10/GDP	0.024	0.025	-10000	0	-0.3	3	3
Insulin Receptor/Insulin/SHC/GRB10	0.062	0.066	-10000	0	-0.23	13	13
INPP5D	-0.03	0.07	-10000	0	-0.23	55	55
SOS1	0.034	0.021	-10000	0	-0.42	1	1
SGK1	-0.008	0.01	-10000	0	-10000	0	0
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.036	0.004	-10000	0	-10000	0	0
IRS1	-0.014	0.14	-10000	0	-0.42	54	54
p62DOK/RasGAP	0.045	0.11	-10000	0	-0.58	13	13
INS	0.037	0.024	-10000	0	-0.42	1	1
mol:PI-3-4-P2	-0.03	0.07	-10000	0	-0.22	55	55
GRB2	0.033	0.01	-10000	0	-10000	0	0
EIF4EBP1	-0.05	0.11	0.24	4	-0.34	18	22
PTPRA	0.037	0.013	-10000	0	-10000	0	0
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
TC10/GTP/CIP4	0.043	0.036	-10000	0	-0.25	7	7
PDPK1	0.032	0.023	-10000	0	-0.42	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.005	0.077	-10000	0	-0.36	6	6
Insulin Receptor/Insulin/IRS1	0.034	0.1	-10000	0	-0.24	55	55
Insulin Receptor/Insulin/IRS3	0.054	0.034	-10000	0	-0.3	3	3
Par3/Par6	0.025	0.1	-10000	0	-0.22	66	66

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.019	0.059	0.21	8	-0.21	14	22
DAPP1	-0.039	0.16	0.24	1	-0.42	50	51
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.06	0.22	-10000	0	-0.57	60	60
mol:DAG	-0.016	0.092	0.22	6	-0.23	43	49
HRAS	0.031	0.038	-10000	0	-0.43	3	3
RAP1A	0.029	0.051	-10000	0	-0.42	6	6
ARF5/GDP	-0.004	0.11	-10000	0	-0.32	29	29
PLCG2	0.02	0.055	-10000	0	-0.42	7	7
PLCG1	0.033	0.009	-10000	0	-10000	0	0
ARF5	0.034	0.021	-10000	0	-0.42	1	1
mol:GTP	-0.019	0.061	0.21	10	-0.21	20	30
ARF1/GTP	-0.009	0.053	0.22	8	-0.2	16	24
RHOA	0.026	0.061	-10000	0	-0.42	9	9
YES1	0.029	0.05	-10000	0	-0.42	6	6
RAP1A/GTP	-0.018	0.062	0.18	28	-0.21	20	48
ADAP1	-0.018	0.056	0.2	9	-0.2	20	29
ARAP3	-0.018	0.06	0.21	10	-0.21	20	30
INPPL1	0.03	0.036	-10000	0	-0.42	3	3
PREX1	-0.036	0.16	-10000	0	-0.42	74	74
ARHGEF6	0.015	0.093	-10000	0	-0.42	22	22
ARHGEF7	0.032	0.011	-10000	0	-10000	0	0
ARF1	0.027	0.025	-10000	0	-0.42	1	1
NRAS	0.028	0.051	-10000	0	-0.42	6	6
FYN	0.027	0.05	-10000	0	-0.42	6	6
ARF6	0.033	0.029	-10000	0	-0.42	2	2
FGR	0.034	0.008	-10000	0	-10000	0	0
mol:Ca2+	-0.009	0.05	0.14	10	-0.12	27	37
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.028	0.057	-10000	0	-0.42	8	8
ZAP70	0.033	0.022	-10000	0	-0.42	1	1
mol:IP3	-0.016	0.067	0.17	10	-0.17	33	43
LYN	0.03	0.014	-10000	0	-10000	0	0
ARF1/GDP	-0.003	0.1	-10000	0	-0.32	25	25
RhoA/GDP	0.012	0.092	0.23	5	-0.26	23	28
PDK1/Src/Hsp90	0.041	0.025	-10000	0	-0.25	2	2
BLNK	0.012	0.1	-10000	0	-0.42	26	26
actin cytoskeleton reorganization	-0.021	0.11	0.23	4	-0.37	20	24
SRC	0.032	0.03	-10000	0	-0.42	2	2
PLEKHA2	-0.009	0.022	-10000	0	-0.25	4	4
RAC1	0.035	0.006	-10000	0	-10000	0	0
PTEN	0.026	0.059	-10000	0	-0.4	9	9
HSP90AA1	0	0	-10000	0	-10000	0	0
ARF6/GTP	-0.02	0.06	0.22	9	-0.2	20	29
RhoA/GTP	-0.023	0.068	0.22	8	-0.25	23	31
Src family/SYK family/BLNK-LAT	-0.028	0.16	-10000	0	-0.45	46	46
BLK	0.021	0.038	-10000	0	-0.42	3	3
PDPK1	0.032	0.023	-10000	0	-0.42	1	1
CYTH1	-0.018	0.056	0.2	9	-0.2	20	29
HCK	0.017	0.087	-10000	0	-0.42	19	19
CYTH3	-0.018	0.056	0.2	9	-0.2	20	29
CYTH2	-0.018	0.056	0.2	9	-0.2	20	29
KRAS	0.026	0.059	-10000	0	-0.43	8	8
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.005	0.038	0.23	2	-0.2	2	4
SGK1	0.008	0.041	0.24	2	-0.2	3	5
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.02	0.11	-10000	0	-0.32	34	34
SOS1	0.034	0.021	-10000	0	-0.42	1	1
SYK	0.005	0.11	-10000	0	-0.42	33	33
ARF6/GDP	-0.004	0.075	0.27	2	-0.26	12	14
mol:PI-3-4-5-P3	-0.019	0.061	0.23	9	-0.21	20	29
ARAP3/RAP1A/GTP	-0.018	0.062	0.18	28	-0.21	20	48
VAV1	0.018	0.083	-10000	0	-0.42	17	17
mol:PI-3-4-P2	0.006	0.024	-10000	0	-0.3	3	3
RAS family/GTP/PI3K Class I	0.044	0.065	0.22	18	-0.22	20	38
PLEKHA1	-0.012	0.029	-10000	0	-0.25	7	7
Rac1/GDP	-0.004	0.11	-10000	0	-0.32	30	30
LAT	0.029	0.031	-10000	0	-0.42	2	2
Rac1/GTP	-0.018	0.12	-10000	0	-0.35	38	38
ITK	-0.033	0.072	0.2	9	-0.22	48	57
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.028	0.12	0.25	6	-0.31	47	53
LCK	-0.018	0.14	-10000	0	-0.42	54	54
BTK	-0.026	0.069	0.21	9	-0.23	30	39

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.015	0.15	0.36	1	-0.46	23	24
PDGFB-D/PDGFRB/SLAP	0.031	0.056	-10000	0	-0.31	11	11
PDGFB-D/PDGFRB/APS/CBL	0.037	0.041	-10000	0	-0.25	8	8
AKT1	-0.01	0.14	0.34	22	-0.39	12	34
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.006	0.14	0.35	1	-0.49	20	21
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
FGR	0.002	0.12	0.3	3	-0.44	21	24
mol:Ca2+	0.008	0.13	0.29	2	-0.51	18	20
MYC	0.012	0.24	0.38	11	-0.72	40	51
SHC1	0.027	0.025	-10000	0	-0.42	1	1
HRAS/GDP	0.034	0.066	0.19	1	-0.22	17	18
LRP1/PDGFRB/PDGFB	0.058	0.06	-10000	0	-0.29	12	12
GRB10	0.022	0.075	-10000	0	-0.42	14	14
PTPN11	0.036	0.004	-10000	0	-10000	0	0
GO:0007205	0.007	0.13	0.29	2	-0.52	18	20
PTEN	0.027	0.061	-10000	0	-0.42	9	9
GRB2	0.033	0.01	-10000	0	-10000	0	0
GRB7	0.024	0.058	-10000	0	-0.42	8	8
PDGFB-D/PDGFRB/SHP2	0.046	0.046	-10000	0	-0.31	8	8
PDGFB-D/PDGFRB/GRB10	0.035	0.073	-10000	0	-0.3	22	22
cell cycle arrest	0.03	0.056	-10000	0	-0.31	11	11
HRAS	0.032	0.036	-10000	0	-0.42	3	3
HIF1A	-0.025	0.13	0.33	19	-0.35	18	37
GAB1	-0.002	0.14	0.31	2	-0.5	23	25
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	-0.003	0.14	0.32	4	-0.46	21	25
PDGFB-D/PDGFRB	0.051	0.056	-10000	0	-0.27	9	9
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.044	0.053	-10000	0	-0.31	11	11
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.009	0.14	0.3	1	-0.46	23	24
positive regulation of MAPKKK cascade	0.046	0.046	-10000	0	-0.31	8	8
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
mol:IP3	0.007	0.13	0.3	2	-0.53	18	20
E5	-0.001	0.002	-10000	0	-10000	0	0
CSK	0.033	0.022	-10000	0	-0.42	1	1
PDGFB-D/PDGFRB/GRB7	0.036	0.064	-10000	0	-0.3	16	16
SHB	0.03	0.046	-10000	0	-0.42	5	5
BLK	-0.066	0.19	0.28	1	-0.43	93	94
PTPN2	0.034	0.01	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.045	0.046	-10000	0	-0.3	8	8
BCAR1	0.029	0.014	-10000	0	-10000	0	0
VAV2	-0.005	0.16	0.31	3	-0.5	27	30
CBL	0.031	0.012	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.042	0.058	-10000	0	-0.31	13	13
LCK	-0.052	0.21	-10000	0	-0.56	64	64
PDGFRB	0.027	0.059	-10000	0	-0.43	8	8
ACP1	0.033	0.035	-10000	0	-0.42	3	3
HCK	-0.006	0.14	0.32	2	-0.52	28	30
ABL1	-0.005	0.14	0.28	2	-0.44	27	29
PDGFB-D/PDGFRB/CBL	-0.009	0.16	-10000	0	-0.56	26	26
PTPN1	0.029	0.031	-10000	0	-0.42	2	2
SNX15	0.035	0.007	-10000	0	-10000	0	0
STAT3	0.028	0.031	-10000	0	-0.42	2	2
STAT1	0.02	0.075	-10000	0	-0.42	14	14
cell proliferation	0.018	0.22	0.36	13	-0.64	40	53
SLA	0.021	0.047	-10000	0	-0.42	5	5
actin cytoskeleton reorganization	0.037	0.071	0.43	2	-0.22	10	12
SRC	0.011	0.095	0.3	3	-0.54	7	10
PI3K	-0.052	0.09	-10000	0	-0.25	71	71
PDGFB-D/PDGFRB/GRB7/SHC	0.041	0.062	-10000	0	-0.26	15	15
SH2B2	0	0	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.005	0.14	0.35	1	-0.51	20	21
LYN	0.013	0.077	0.29	3	-0.37	8	11
LRP1	0.035	0.021	-10000	0	-0.42	1	1
SOS1	0.034	0.021	-10000	0	-0.42	1	1
STAT5B	0.03	0.024	-10000	0	-0.42	1	1
STAT5A	0.028	0.037	-10000	0	-0.42	3	3
NCK1-2/p130 Cas	0.066	0.068	-10000	0	-0.22	9	9
SPHK1	0.005	0.11	-10000	0	-0.43	30	30
EDG1	0.011	0.1	-10000	0	-0.42	25	25
mol:DAG	0.007	0.13	0.3	2	-0.53	18	20
PLCG1	0.007	0.14	0.33	1	-0.54	18	19
NHERF/PDGFRB	0.001	0.13	-10000	0	-0.29	80	80
YES1	-0.006	0.14	0.28	2	-0.51	28	30
cell migration	0.001	0.13	-10000	0	-0.28	80	80
SHC/Grb2/SOS1	0.058	0.068	-10000	0	-0.23	9	9
SLC9A3R2	-0.004	0.12	-10000	0	-0.42	40	40
SLC9A3R1	-0.009	0.13	-10000	0	-0.42	46	46
NHERF1-2/PDGFRB/PTEN	0.011	0.14	-10000	0	-0.27	84	84
FYN	-0.013	0.16	0.28	2	-0.53	32	34
DOK1	0.021	0.072	0.19	32	-0.24	15	47
HRAS/GTP	0.024	0.025	-10000	0	-0.3	3	3
PDGFB	0.029	0.046	-10000	0	-0.42	5	5
RAC1	-0.02	0.2	0.35	1	-0.57	40	41
PRKCD	0.021	0.071	0.19	38	-0.27	10	48
FER	0.022	0.069	0.2	37	-0.25	10	47
MAPKKK cascade	0.045	0.11	0.34	26	-0.23	4	30
RASA1	0.019	0.073	0.19	40	-0.24	15	55
NCK1	0.034	0.022	-10000	0	-0.42	1	1
NCK2	0.036	0.004	-10000	0	-10000	0	0
p62DOK/Csk	0.042	0.065	0.34	1	-0.22	16	17
PDGFB-D/PDGFRB/SHB	0.041	0.058	-10000	0	-0.31	13	13
chemotaxis	-0.005	0.13	0.26	3	-0.43	27	30
STAT1-3-5/STAT1-3-5	0.048	0.075	-10000	0	-0.22	24	24
Bovine Papilomavirus E5/PDGFRB	0.019	0.043	-10000	0	-0.31	8	8
PTPRJ	0.03	0.046	-10000	0	-0.42	5	5

×

ErbB2/ErbB3 signaling events

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
USP8	-0.011	0.02	-10000	0	-0.26	3	3
RAS family/GTP	0.029	0.11	0.25	2	-0.3	17	19
NFATC4	-0.031	0.069	0.24	2	-0.29	10	12
ERBB2IP	0.034	0.022	-10000	0	-0.42	1	1
HSP90 (dimer)	0	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.004	0.088	-10000	0	-0.26	36	36
JUN	0.007	0.074	0.21	3	-10000	0	3
HRAS	0.032	0.036	-10000	0	-0.42	3	3
DOCK7	-0.035	0.078	0.27	2	-0.27	28	30
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.019	0.088	-10000	0	-0.27	34	34
AKT1	0.002	0.025	-10000	0	-0.3	3	3
BAD	-0.011	0.022	-10000	0	-0.26	4	4
MAPK10	-0.025	0.062	0.2	7	-0.2	16	23
mol:GTP	0	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.004	0.094	-10000	0	-0.29	30	30
RAF1	0.01	0.11	0.27	12	-0.32	17	29
ErbB2/ErbB3/neuregulin 2	0.011	0.093	-10000	0	-0.28	44	44
STAT3	0.006	0.17	-10000	0	-0.88	18	18
cell migration	-0.019	0.065	0.22	9	-0.21	11	20
mol:PI-3-4-5-P3	-0.001	0.001	-10000	0	-10000	0	0
cell proliferation	-0.046	0.25	0.41	1	-0.63	59	60
FOS	-0.046	0.21	0.36	1	-0.44	105	106
NRAS	0.029	0.05	-10000	0	-0.42	6	6
mol:Ca2+	-0.004	0.088	-10000	0	-0.26	36	36
MAPK3	-0.02	0.2	0.37	2	-0.51	48	50
MAPK1	-0.032	0.21	0.41	1	-0.55	50	51
JAK2	-0.034	0.079	0.27	2	-0.27	26	28
NF2	0.01	0.047	-10000	0	-0.68	2	2
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.001	0.071	0.19	2	-0.27	25	27
NRG1	0.028	0.015	-10000	0	-10000	0	0
GRB2/SOS1	0.047	0.023	-10000	0	-0.3	1	1
MAPK8	-0.021	0.098	0.22	4	-0.28	30	34
MAPK9	-0.024	0.06	0.2	7	-0.21	11	18
ERBB2	-0.031	0.055	0.6	1	-0.32	13	14
ERBB3	0.006	0.11	-10000	0	-0.42	32	32
SHC1	0.027	0.025	-10000	0	-0.42	1	1
RAC1	0.035	0.006	-10000	0	-10000	0	0
apoptosis	0.006	0.033	0.32	3	-0.21	4	7
STAT3 (dimer)	0.006	0.17	-10000	0	-0.86	18	18
RNF41	-0.014	0.019	-10000	0	-0.24	3	3
FRAP1	-0.01	0.016	-10000	0	-0.26	2	2
RAC1-CDC42/GTP	-0.035	0.052	-10000	0	-0.2	29	29
ErbB2/ErbB2/HSP90 (dimer)	-0.025	0.04	-10000	0	-0.27	13	13
CHRNA1	-0.007	0.17	0.35	2	-0.41	47	49
myelination	-0.025	0.083	0.27	12	-0.32	7	19
PPP3CB	-0.035	0.073	0.26	2	-0.25	29	31
KRAS	0.027	0.058	-10000	0	-0.42	8	8
RAC1-CDC42/GDP	0.038	0.095	0.25	3	-0.28	13	16
NRG2	0.025	0.058	-10000	0	-0.42	8	8
mol:GDP	0.001	0.07	0.19	2	-0.26	25	27
SOS1	0.034	0.021	-10000	0	-0.42	1	1
MAP2K2	-0.002	0.11	0.26	10	-0.32	23	33
SRC	0.032	0.03	-10000	0	-0.42	2	2
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.036	0.077	0.27	2	-0.27	28	30
MAP2K1	-0.029	0.2	0.38	1	-0.58	36	37
heart morphogenesis	-0.004	0.088	-10000	0	-0.26	36	36
RAS family/GDP	0.04	0.11	0.26	2	-0.29	16	18
GRB2	0.033	0.01	-10000	0	-10000	0	0
PRKACA	0.014	0.054	-10000	0	-0.68	3	3
CHRNE	0.008	0.018	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
activation of caspase activity	-0.002	0.025	0.3	3	-10000	0	3
nervous system development	-0.004	0.088	-10000	0	-0.26	36	36
CDC42	0.034	0.008	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.036	0.15	-10000	0	-0.42	39	39
BAG4	0.027	0.025	-10000	0	-0.42	1	1
BAD	-0.007	0.05	0.19	2	-0.17	13	15
NFKBIA	0.033	0.03	-10000	0	-0.42	2	2
BIRC3	-0.01	0.12	-10000	0	-0.42	42	42
BAX	-0.004	0.056	0.2	9	-0.17	15	24
EnzymeConsortium:3.1.4.12	-0.007	0.035	0.075	4	-0.093	36	40
IKBKB	-0.017	0.14	0.3	2	-0.41	29	31
MAP2K2	-0.009	0.056	0.19	11	-0.2	7	18
MAP2K1	-0.008	0.052	0.19	10	-0.2	4	14
SMPD1	-0.007	0.041	-10000	0	-0.16	14	14
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.003	0.15	0.3	6	-0.41	29	35
MAP2K4	-0.016	0.057	0.18	1	-0.19	23	24
protein ubiquitination	-0.033	0.14	0.25	1	-0.42	33	34
EnzymeConsortium:2.7.1.37	-0.012	0.057	0.22	5	-0.2	7	12
response to UV	0	0.001	0.002	9	-0.002	5	14
RAF1	-0.008	0.053	0.2	8	-0.19	6	14
CRADD	0.029	0.054	-10000	0	-0.42	7	7
mol:ceramide	-0.006	0.051	0.11	2	-0.15	29	31
I-kappa-B-alpha/RELA/p50/ubiquitin	0.044	0.023	-10000	0	-0.25	2	2
MADD	0.035	0.005	-10000	0	-10000	0	0
MAP3K1	-0.017	0.061	-10000	0	-0.18	40	40
TRADD	0.029	0.014	-10000	0	-10000	0	0
RELA/p50	0.035	0.006	-10000	0	-10000	0	0
MAPK3	-0.005	0.056	0.2	8	-0.19	4	12
MAPK1	-0.008	0.063	0.2	7	-0.21	10	17
p50/RELA/I-kappa-B-alpha	0.048	0.026	-10000	0	-0.3	2	2
FADD	-0.003	0.15	0.28	5	-0.42	29	34
KSR1	-0.008	0.051	0.19	3	-0.17	13	16
MAPK8	-0.021	0.059	0.21	3	-0.21	11	14
TRAF2	0.034	0.029	-10000	0	-0.42	2	2
response to radiation	0	0	0.002	2	-10000	0	2
CHUK	-0.044	0.14	-10000	0	-0.4	41	41
TNF R/SODD	0.039	0.028	-10000	0	-0.3	1	1
TNF	0.026	0.061	-10000	0	-0.42	9	9
CYCS	0.014	0.069	0.17	27	-0.17	9	36
IKBKG	-0.04	0.14	-10000	0	-0.41	37	37
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.032	0.15	-10000	0	-0.44	38	38
RELA	0.035	0.006	-10000	0	-10000	0	0
RIPK1	0.035	0.007	-10000	0	-10000	0	0
AIFM1	0.012	0.068	0.16	25	-0.17	12	37
TNF/TNF R/SODD	0.048	0.049	-10000	0	-0.25	7	7
TNFRSF1A	0.033	0.022	-10000	0	-0.42	1	1
response to heat	0	0	0.002	2	-10000	0	2
CASP8	0.011	0.12	-10000	0	-0.63	16	16
NSMAF	-0.012	0.14	0.27	1	-0.42	29	30
response to hydrogen peroxide	0	0.001	0.002	9	-0.002	5	14
BCL2	-0.057	0.18	-10000	0	-0.42	99	99

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.025	0.1	0.9	1	-0.78	1	2
VDR	0.02	0.083	-10000	0	-0.42	17	17
FAM120B	0	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.004	0.1	-10000	0	-0.27	48	48
RXRs/LXRs/DNA/Oxysterols	0.013	0.16	-10000	0	-0.42	48	48
MED1	0	0	-10000	0	-10000	0	0
mol:9cRA	-0.001	0.019	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	0.002	0.093	-10000	0	-0.24	49	49
RXRs/NUR77	0.054	0.081	-10000	0	-0.25	12	12
RXRs/PPAR	0.009	0.073	-10000	0	-0.25	28	28
NCOR2	0.036	0.004	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.015	0.058	-10000	0	-0.3	17	17
RARs/VDR/DNA/Vit D3	0.051	0.085	-10000	0	-0.23	37	37
RARA	0.027	0.054	-10000	0	-0.42	7	7
NCOA1	0.031	0.045	-10000	0	-0.42	5	5
VDR/VDR/DNA	0.02	0.082	-10000	0	-0.42	17	17
RARs/RARs/DNA/9cRA	0.039	0.065	-10000	0	-0.22	25	25
RARG	0.036	0.004	-10000	0	-10000	0	0
RPS6KB1	0.052	0.14	0.54	40	-10000	0	40
RARs/THRs/DNA/SMRT	0.003	0.092	-10000	0	-0.24	49	49
THRA	0.02	0.075	-10000	0	-0.42	14	14
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.015	0.058	-10000	0	-0.3	17	17
RXRs/PPAR/9cRA/PGJ2/DNA	0.039	0.083	-10000	0	-0.24	17	17
NR1H4	0.035	0.021	-10000	0	-0.42	1	1
RXRs/LXRs/DNA	0.058	0.11	-10000	0	-0.25	14	14
NR1H2	0.028	0.031	-10000	0	-10000	0	0
NR1H3	0.025	0.053	-10000	0	-0.43	4	4
RXRs/VDR/DNA/Vit D3	0.043	0.084	-10000	0	-0.24	20	20
NR4A1	0.034	0.021	-10000	0	-0.42	1	1
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.026	0.063	-10000	0	-0.22	15	15
RXRG	0.016	0.063	-10000	0	-0.43	8	8
RXR alpha/CCPG	0.021	0.029	-10000	0	-0.31	2	2
RXRA	0.027	0.042	-10000	0	-0.44	2	2
RXRB	0.027	0.044	-10000	0	-0.42	2	2
THRB	0.024	0.07	-10000	0	-0.42	12	12
PPARG	0.012	0.091	-10000	0	-0.42	21	21
PPARD	0.035	0.006	-10000	0	-10000	0	0
TNF	-0.001	0.19	-10000	0	-0.8	17	17
mol:Oxysterols	-0.001	0.017	-10000	0	-10000	0	0
cholesterol transport	0.013	0.16	-10000	0	-0.42	48	48
PPARA	0.032	0.023	-10000	0	-0.42	1	1
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.014	0.089	-10000	0	-0.42	20	20
RXRs/NUR77/BCL2	-0.02	0.097	-10000	0	-0.22	84	84
SREBF1	-0.047	0.29	-10000	0	-0.93	46	46
RXRs/RXRs/DNA/9cRA	0.039	0.083	-10000	0	-0.24	17	17
ABCA1	-0.006	0.21	-10000	0	-0.89	18	18
RARs/THRs	0.061	0.1	-10000	0	-0.24	47	47
RXRs/FXR	0.054	0.082	-10000	0	-0.25	13	13
BCL2	-0.057	0.18	-10000	0	-0.42	99	99

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.072	0.23	-10000	0	-0.78	22	22
RAD9A	0.033	0.01	-10000	0	-10000	0	0
AP1	-0.026	0.15	-10000	0	-0.34	89	89
IFNAR2	0.027	0.03	-10000	0	-0.43	1	1
AKT1	-0.034	0.11	-10000	0	-0.2	131	131
ER alpha/Oestrogen	-0.063	0.14	-10000	0	-0.3	130	130
NFX1/SIN3/HDAC complex	0.012	0.072	-10000	0	-0.34	13	13
EGF	-0.07	0.19	-10000	0	-0.42	110	110
SMG5	0	0	-10000	0	-10000	0	0
SMG6	0	0	-10000	0	-10000	0	0
SP3/HDAC2	0.038	0.036	-10000	0	-0.3	1	1
TERT/c-Abl	-0.06	0.22	-10000	0	-0.7	24	24
SAP18	0.033	0.01	-10000	0	-10000	0	0
MRN complex	0.047	0.044	-10000	0	-0.26	4	4
WT1	-0.024	0.14	-10000	0	-0.42	52	52
WRN	0.027	0.025	-10000	0	-0.42	1	1
SP1	0.026	0.033	-10000	0	-0.43	1	1
SP3	0.035	0.007	-10000	0	-10000	0	0
TERF2IP	0.029	0.014	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.046	0.21	-10000	0	-0.63	25	25
Mad/Max	0.047	0.019	-10000	0	-10000	0	0
TERT	-0.075	0.24	-10000	0	-0.84	20	20
CCND1	-0.15	0.44	-10000	0	-1.1	85	85
MAX	0.034	0.009	-10000	0	-10000	0	0
RBBP7	0.033	0.029	-10000	0	-0.42	2	2
RBBP4	0.034	0.021	-10000	0	-0.42	1	1
TERF2	0.027	0.031	-10000	0	-0.37	2	2
PTGES3	0.035	0.021	-10000	0	-0.42	1	1
SIN3A	0.034	0.007	-10000	0	-10000	0	0
Telomerase/911	0.021	0.069	-10000	0	-0.46	5	5
CDKN1B	-0.029	0.14	-10000	0	-0.37	66	66
RAD1	0.033	0.03	-10000	0	-0.42	2	2
XRCC5	0.036	0.004	-10000	0	-10000	0	0
XRCC6	0.033	0.009	-10000	0	-10000	0	0
SAP30	0.03	0.046	-10000	0	-0.42	5	5
TRF2/PARP2	0.043	0.032	-10000	0	-0.29	2	2
UBE3A	0.033	0.029	-10000	0	-0.43	2	2
JUN	-0.002	0.12	-10000	0	-0.42	39	39
E6	-0.001	0.004	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.02	0.027	-10000	0	-0.3	2	2
FOS	-0.032	0.15	-10000	0	-0.42	66	66
IFN-gamma/IRF1	0	0.12	-10000	0	-0.3	70	70
PARP2	0.036	0.002	-10000	0	-10000	0	0
BLM	0.011	0.097	-10000	0	-0.42	24	24
Telomerase	0.013	0.044	0.18	1	-10000	0	1
IRF1	0.015	0.085	-10000	0	-0.27	35	35
ESR1	-0.088	0.2	-10000	0	-0.42	130	130
KU/TER	0.049	0.015	-10000	0	-10000	0	0
ATM/TRF2	0.035	0.035	-10000	0	-0.19	2	2
ubiquitin-dependent protein catabolic process	0.022	0.06	-10000	0	-0.26	12	12
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.023	0.059	-10000	0	-0.27	11	11
HDAC1	0.034	0.021	-10000	0	-0.42	1	1
HDAC2	0.024	0.032	-10000	0	-0.42	1	1
ATM	0.02	0.025	0.19	2	-10000	0	2
SMAD3	0.01	0.044	-10000	0	-0.3	10	10
ABL1	0.035	0.005	-10000	0	-10000	0	0
MXD1	0.034	0.008	-10000	0	-10000	0	0
MRE11A	0.031	0.012	-10000	0	-10000	0	0
HUS1	0.035	0.006	-10000	0	-10000	0	0
RPS6KB1	0.031	0.013	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.056	0.23	-10000	0	-0.68	29	29
NR2F2	-0.011	0.14	-10000	0	-0.42	49	49
MAPK3	0.007	0.032	-10000	0	-0.3	4	4
MAPK1	0.007	0.032	-10000	0	-0.3	4	4
TGFB1/TGF beta receptor Type II	0.035	0.021	-10000	0	-0.42	1	1
NFKB1	0.035	0.005	-10000	0	-10000	0	0
HNRNPC	0	0	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.02	0.025	0.19	2	-10000	0	2
NBN	0.027	0.025	-10000	0	-0.42	1	1
EGFR	-0.013	0.13	-10000	0	-0.42	47	47
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.063	0.16	-10000	0	-0.31	151	151
MYC	-0.002	0.1	-10000	0	-0.42	29	29
IL2	0.024	0.043	-10000	0	-0.42	3	3
KU	0.049	0.015	-10000	0	-10000	0	0
RAD50	0.03	0.046	-10000	0	-0.42	5	5
HSP90AA1	0	0	-10000	0	-10000	0	0
TGFB1	0.035	0.021	-10000	0	-0.42	1	1
TRF2/BLM	0.026	0.073	-10000	0	-0.28	25	25
FRAP1	0.034	0.008	-10000	0	-10000	0	0
KU/TERT	-0.047	0.23	-10000	0	-0.7	24	24
SP1/HDAC2	0.038	0.043	-10000	0	-0.3	2	2
PINX1	0.028	0.015	-10000	0	-10000	0	0
Telomerase/EST1A	-0.059	0.2	-10000	0	-0.63	25	25
Smad3/Myc	0.006	0.074	-10000	0	-0.26	35	35
911 complex	0.062	0.032	-10000	0	-0.26	2	2
IFNG	-0.014	0.12	-10000	0	-0.34	56	56
Telomerase/PinX1	-0.057	0.2	-10000	0	-0.63	25	25
Telomerase/AKT1/mTOR/p70S6K	-0.007	0.1	-10000	0	-0.41	17	17
SIN3B	0.035	0.005	-10000	0	-10000	0	0
YWHAE	0.032	0.011	-10000	0	-10000	0	0
Telomerase/EST1B	-0.059	0.2	-10000	0	-0.63	25	25
response to DNA damage stimulus	-0.001	0.034	0.13	1	-0.1	36	37
MRN complex/TRF2/Rap1	0.058	0.061	-10000	0	-0.25	5	5
TRF2/WRN	0.033	0.036	-10000	0	-0.29	3	3
Telomerase/hnRNP C1/C2	-0.059	0.2	-10000	0	-0.63	25	25
E2F1	0.02	0.057	-10000	0	-0.42	7	7
ZNFX1	0	0.001	-10000	0	-10000	0	0
PIF1	0	0	-10000	0	-10000	0	0
NCL	0.035	0.006	-10000	0	-10000	0	0
DKC1	0.036	0.003	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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
ERK1-2/ELK1	0.016	0.15	-9999	-0.34	47	47
MAP3K8	0.002	0.11	-9999	-0.42	32	32
FOS	0.019	0.099	-9999	-0.4	9	9
PRKCA	0.025	0.022	-9999	-10000	0	0
PTPN7	0.02	0.032	-9999	-0.44	1	1
HRAS	0.031	0.036	-9999	-0.42	3	3
PRKCB	-0.002	0.006	-9999	-0.016	73	73
NRAS	0.029	0.05	-9999	-0.42	6	6
RAS family/GTP	0.05	0.055	-9999	-0.23	15	15
MAPK3	0.027	0.07	-9999	-0.45	6	6
MAP2K1	0.008	0.066	-9999	-0.25	9	9
ELK1	0.025	0.038	-9999	-0.42	2	2
BRAF	0.004	0.05	-9999	-0.35	8	8
mol:GTP	-0.001	0.002	-9999	-0.005	73	73
MAPK1	0.012	0.1	-9999	-0.4	19	19
RAF1	0.01	0.023	-9999	-0.24	1	1
KRAS	0.027	0.057	-9999	-0.42	8	8

×

p75(NTR)-mediated signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.047	0.04	-10000	0	-0.3	6	6
Necdin/E2F1	0.013	0.11	-10000	0	-0.31	52	52
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.03	0.11	-10000	0	-0.23	71	71
NGF (dimer)/p75(NTR)/BEX1	0.037	0.035	-10000	0	-0.25	6	6
NT-4/5 (dimer)/p75(NTR)	0.022	0.026	-10000	0	-0.3	3	3
IKBKB	0.029	0.014	-10000	0	-10000	0	0
AKT1	0.019	0.069	0.19	41	-0.22	22	63
IKBKG	0.036	0	-10000	0	-10000	0	0
BDNF	0.03	0.024	-10000	0	-0.42	1	1
MGDIs/NGR/p75(NTR)/LINGO1	0.033	0.051	-10000	0	-0.25	14	14
FURIN	0.026	0.058	-10000	0	-0.42	8	8
proBDNF (dimer)/p75(NTR)/Sortilin	0.058	0.047	-10000	0	-0.25	9	9
LINGO1	0	0	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	0.025	0.055	-10000	0	-0.22	16	16
proBDNF (dimer)	0.03	0.024	-10000	0	-0.42	1	1
NTRK1	0.025	0.032	-10000	0	-0.42	2	2
RTN4R	0.023	0.067	-10000	0	-0.42	11	11
neuron apoptosis	-0.009	0.1	0.28	1	-0.46	9	10
IRAK1	0.036	0.004	-10000	0	-10000	0	0
SHC1	0.012	0.022	-10000	0	-0.25	3	3
ARHGDIA	0.032	0.022	-10000	0	-0.42	1	1
RhoA/GTP	0.02	0.043	-10000	0	-0.3	9	9
Gamma Secretase	0.068	0.07	-10000	0	-0.22	14	14
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.04	0.083	-10000	0	-0.24	38	38
MAGEH1	0.006	0.11	-10000	0	-0.42	33	33
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.03	0.097	-10000	0	-0.24	54	54
Mammalian IAPs/DIABLO	0.032	0.083	-10000	0	-0.23	41	41
proNGF (dimer)	0	0	-10000	0	-10000	0	0
MAGED1	0.015	0.095	-10000	0	-0.42	23	23
APP	0.008	0.1	-10000	0	-0.42	28	28
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
ZNF274	0.034	0.029	-10000	0	-0.42	2	2
RhoA/GDP/RHOGDI	0.037	0.044	0.18	3	-0.22	12	15
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	-0.011	0.048	0.2	16	-0.22	9	25
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.02	0.031	-10000	0	-0.21	6	6
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.042	0.03	-10000	0	-0.25	4	4
NCSTN	0.028	0.025	-10000	0	-0.42	1	1
mol:GTP	0.025	0.067	-10000	0	-0.25	27	27
PSENEN	0.035	0.006	-10000	0	-10000	0	0
mol:ceramide	0.015	0.043	0.19	11	-0.23	10	21
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.013	0.037	-10000	0	-10000	0	0
p75(NTR)/beta APP	0.026	0.082	-10000	0	-0.3	29	29
BEX1	0.026	0.037	-10000	0	-0.42	3	3
mol:GDP	-0.006	0.019	-10000	0	-0.25	3	3
NGF (dimer)	0.007	0.11	-10000	0	-0.24	76	76
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.049	0.055	-10000	0	-0.23	15	15
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
RAC1/GTP	0.037	0.023	-10000	0	-0.21	3	3
MYD88	0.031	0.041	-10000	0	-0.42	4	4
CHUK	0.025	0.067	-10000	0	-0.42	11	11
NGF (dimer)/p75(NTR)/PKA	0.026	0.068	-10000	0	-0.25	27	27
RHOB	-0.011	0.14	-10000	0	-0.42	51	51
RHOA	0.026	0.061	-10000	0	-0.42	9	9
MAGE-G1/E2F1	0.043	0.044	-10000	0	-0.3	7	7
NT3 (dimer)	0.024	0.054	-10000	0	-0.42	7	7
TP53	-0.02	0.066	0.35	1	-0.23	17	18
PRDM4	0.019	0.045	0.19	16	-0.23	9	25
BDNF (dimer)	-0.02	0.17	-10000	0	-0.31	114	114
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
SORT1	0.03	0.05	-10000	0	-0.42	6	6
activation of caspase activity	0.024	0.11	-10000	0	-0.23	71	71
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.057	0.044	-10000	0	-0.23	9	9
RHOC	0.032	0.036	-10000	0	-0.42	3	3
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	-0.018	0.079	0.22	1	-0.29	13	14
DIABLO	0.036	0.004	-10000	0	-10000	0	0
SMPD2	0.015	0.043	0.19	11	-0.23	10	21
APH1B	0.023	0.073	-10000	0	-0.42	13	13
APH1A	0.031	0.036	-10000	0	-0.42	3	3
proNGF (dimer)/p75(NTR)/Sortilin	0.039	0.041	-10000	0	-0.25	9	9
PSEN1	0.032	0.036	-10000	0	-0.42	3	3
APAF-1/Pro-Caspase 9	0.047	0.037	-10000	0	-0.3	5	5
NT3 (dimer)/p75(NTR)	0.038	0.051	-10000	0	-0.3	10	10
MAPK8	-0.011	0.065	-10000	0	-0.28	7	7
MAPK9	-0.017	0.078	-10000	0	-0.32	11	11
APAF1	0.032	0.041	-10000	0	-0.42	4	4
NTF3	0.024	0.054	-10000	0	-0.42	7	7
NTF4	0	0	-10000	0	-10000	0	0
NDN	-0.011	0.14	-10000	0	-0.42	52	52
RAC1/GDP	0.026	0.004	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.019	0.11	-10000	0	-0.22	84	84
p75 CTF/Sortilin/TRAF6/NRIF	0.081	0.047	-10000	0	-0.24	8	8
RhoA-B-C/GTP	0.025	0.067	-10000	0	-0.25	27	27
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.086	0.058	-10000	0	-0.22	12	12
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.074	0.052	-10000	0	-0.23	10	10
PRKACB	0.009	0.097	-10000	0	-0.42	24	24
proBDNF (dimer)/p75 ECD	0.048	0.02	-10000	0	-0.3	1	1
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.12	-10000	0	-0.42	42	42
BIRC2	0.031	0.012	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.038	0.078	0.13	2	-0.26	39	41
BAD	-0.02	0.08	-10000	0	-0.3	10	10
RIPK2	0.028	0.015	-10000	0	-10000	0	0
NGFR	0.03	0.036	-10000	0	-0.42	3	3
CYCS	0.004	0.064	0.19	12	-0.22	32	44
ADAM17	0.035	0.006	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.047	0.04	-10000	0	-0.23	4	4
BCL2L11	-0.02	0.079	-10000	0	-0.3	10	10
BDNF (dimer)/p75(NTR)	0.043	0.034	-10000	0	-0.3	4	4
PI3K	0.046	0.062	-10000	0	-0.23	20	20
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.055	0.044	-10000	0	-0.23	9	9
NDNL2	0.034	0.008	-10000	0	-10000	0	0
YWHAE	0.032	0.011	-10000	0	-10000	0	0
PRKCI	0.024	0.067	-10000	0	-0.42	11	11
NGF (dimer)/p75(NTR)	0.022	0.026	-10000	0	-0.3	3	3
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.044	0.074	-10000	0	-0.23	32	32
TRAF6	0.034	0.021	-10000	0	-0.42	1	1
RAC1	0.035	0.006	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
PLG	0.031	0.03	-10000	0	-0.42	2	2
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	0.018	0.046	0.16	2	-0.24	14	16
SQSTM1	0.034	0.021	-10000	0	-0.42	1	1
NGFRAP1	-0.026	0.16	-10000	0	-0.42	68	68
CASP3	-0.018	0.077	-10000	0	-0.28	10	10
E2F1	0.028	0.054	-10000	0	-0.42	7	7
CASP9	0.034	0.022	-10000	0	-0.42	1	1
IKK complex	0.041	0.064	-10000	0	-0.32	1	1
NGF (dimer)/TRKA	0.019	0.023	-10000	0	-0.3	2	2
MMP7	-0.033	0.16	-10000	0	-0.42	69	69
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.07	0.05	-10000	0	-0.22	11	11
MMP3	-0.047	0.17	-10000	0	-0.42	83	83
APAF-1/Caspase 9	-0.046	0.064	-10000	0	-0.2	68	68

×

EPO signaling pathway

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
BCL2L1	-0.004	0.14	-10000	0	-0.48	1	1
CRKL	-0.001	0.076	0.2	13	-0.24	11	24
mol:DAG	0.019	0.079	0.25	2	-10000	0	2
HRAS	0.022	0.1	0.27	22	-10000	0	22
MAPK8	0.035	0.073	0.2	56	-0.25	2	58
RAP1A	0	0.078	0.2	12	-0.25	12	24
GAB1	-0.001	0.076	0.2	11	-0.25	11	22
MAPK14	0.036	0.071	0.2	54	-10000	0	54
EPO	0.023	0.027	-10000	0	-10000	0	0
PLCG1	0.019	0.08	0.25	2	-10000	0	2
EPOR/TRPC2/IP3 Receptors	0.026	0.028	-10000	0	-10000	0	0
RAPGEF1	0.036	0.004	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.046	0.052	-10000	0	-0.27	4	4
GAB1/SHC/GRB2/SOS1	0.028	0.075	0.29	1	-0.21	1	2
EPO/EPOR (dimer)	0.036	0.039	-10000	0	-10000	0	0
IRS2	-0.01	0.087	0.25	4	-0.26	29	33
STAT1	-0.003	0.13	0.26	2	-0.33	35	37
STAT5B	0.02	0.082	0.26	1	-0.26	2	3
cell proliferation	0.013	0.079	0.19	75	-0.24	2	77
GAB1/SHIP/PIK3R1/SHP2/SHC	0.008	0.074	-10000	0	-0.29	4	4
TEC	0.001	0.075	0.2	12	-0.23	11	23
SOCS3	0.028	0.046	-10000	0	-0.42	5	5
STAT1 (dimer)	-0.003	0.13	0.26	2	-0.32	35	37
JAK2	0.028	0.036	-10000	0	-0.44	2	2
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
EPO/EPOR (dimer)/JAK2	0.036	0.088	0.22	6	-0.17	34	40
EPO/EPOR	0.036	0.039	-10000	0	-10000	0	0
LYN	0.02	0.026	-10000	0	-10000	0	0
TEC/VAV2	0.014	0.08	0.29	2	-0.22	11	13
elevation of cytosolic calcium ion concentration	0.026	0.028	-10000	0	-10000	0	0
SHC1	0.027	0.025	-10000	0	-0.42	1	1
EPO/EPOR (dimer)/LYN	0.043	0.053	-10000	0	-10000	0	0
mol:IP3	0.019	0.079	0.25	2	-10000	0	2
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.006	0.095	0.29	1	-0.24	43	44
SH2B3	-0.003	0.009	-10000	0	-10000	0	0
NFKB1	0.037	0.071	0.2	56	-10000	0	56
EPO/EPOR (dimer)/JAK2/SOCS3	0.023	0.034	-10000	0	-0.21	6	6
PTPN6	-0.002	0.067	0.17	1	-0.19	20	21
TEC/VAV2/GRB2	0.026	0.083	0.3	2	-0.21	9	11
EPOR	0.026	0.028	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.027	0.075	0.29	1	-0.22	1	2
SOS1	0.034	0.021	-10000	0	-0.42	1	1
PLCG2	0.02	0.055	-10000	0	-0.42	7	7
CRKL/CBL/C3G	0.02	0.085	0.3	1	-0.23	10	11
VAV2	0.002	0.074	0.21	9	-0.25	6	15
CBL	0	0.07	0.19	12	-0.25	6	18
SHC/Grb2/SOS1	0.015	0.062	-10000	0	-0.21	4	4
STAT5A	0.019	0.083	0.26	1	-0.26	3	4
GRB2	0.033	0.01	-10000	0	-10000	0	0
STAT5 (dimer)	0.017	0.12	0.28	1	-0.31	45	46
LYN/PLCgamma2	0.029	0.043	-10000	0	-0.3	6	6
PTPN11	0.036	0.004	-10000	0	-10000	0	0
BTK	-0.004	0.083	0.24	5	-0.25	19	24
BCL2	-0.11	0.33	-10000	0	-0.74	105	105

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.027	0.032	-9999	-0.42	2	2
Syndecan-3/Src/Cortactin	0.006	0.14	-9999	-0.51	24	24
Syndecan-3/Neurocan	-0.018	0.12	-9999	-0.5	27	27
POMC	0.031	0.036	-9999	-0.42	3	3
EGFR	-0.013	0.13	-9999	-0.42	47	47
Syndecan-3/EGFR	-0.011	0.15	-9999	-0.53	29	29
AGRP	0.028	0.025	-9999	-0.42	1	1
NCSTN	0.028	0.025	-9999	-0.42	1	1
PSENEN	0.035	0.006	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.023	0.073	-9999	-0.42	13	13
APH1A	0.031	0.036	-9999	-0.42	3	3
NCAN	0	0	-9999	-10000	0	0
long-term memory	0.018	0.12	-9999	-0.49	23	23
Syndecan-3/IL8	-0.007	0.14	-9999	-0.53	28	28
PSEN1	0.032	0.036	-9999	-0.42	3	3
Src/Cortactin	0.038	0.038	-9999	-0.3	4	4
FYN	0.027	0.05	-9999	-0.42	6	6
limb bud formation	-0.015	0.12	-9999	-0.52	26	26
MC4R	0.033	0.022	-9999	-0.42	1	1
SRC	0.032	0.03	-9999	-0.42	2	2
PTN	-0.028	0.15	-9999	-0.42	63	63
FGFR/FGF/Syndecan-3	-0.016	0.12	-9999	-0.53	26	26
neuron projection morphogenesis	-0.031	0.12	-9999	-0.49	24	24
Syndecan-3/AgRP	0.008	0.13	-9999	-0.5	27	27
Syndecan-3/AgRP/MC4R	0.023	0.13	-9999	-0.49	25	25
Fyn/Cortactin	0.035	0.044	-9999	-0.3	6	6
SDC3	-0.016	0.12	-9999	-0.54	26	26
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.007	0.14	-9999	-0.52	28	28
IL8	-0.005	0.12	-9999	-0.42	37	37
Syndecan-3/Fyn/Cortactin	0.018	0.13	-9999	-0.5	23	23
Syndecan-3/CASK	-0.018	0.12	-9999	-0.5	27	27
alpha-MSH/MC4R	0.047	0.034	-9999	-0.3	4	4
Gamma Secretase	0.068	0.07	-9999	-0.22	14	14

×

EPHB forward 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.039	0.038	-10000	0	-0.25	7	7
cell-cell adhesion	0.035	0.058	0.23	29	-10000	0	29
Ephrin B/EPHB2/RasGAP	0.069	0.079	-10000	0	-0.24	21	21
ITSN1	0.034	0.029	-10000	0	-0.42	2	2
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
SHC1	0.027	0.025	-10000	0	-0.42	1	1
Ephrin B1/EPHB3	0.034	0.058	-10000	0	-0.25	19	19
Ephrin B1/EPHB1	0.041	0.036	-10000	0	-0.25	7	7
HRAS/GDP	0.002	0.11	-10000	0	-0.28	35	35
Ephrin B/EPHB1/GRB7	0.064	0.082	-10000	0	-0.23	27	27
Endophilin/SYNJ1	-0.012	0.051	0.19	6	-0.21	14	20
KRAS	0.027	0.057	-10000	0	-0.42	8	8
Ephrin B/EPHB1/Src	0.069	0.076	-10000	0	-0.24	19	19
endothelial cell migration	0.035	0.091	-10000	0	-0.24	45	45
GRB2	0.033	0.01	-10000	0	-10000	0	0
GRB7	0.024	0.058	-10000	0	-0.42	8	8
PAK1	-0.021	0.065	0.28	2	-0.24	1	3
HRAS	0.032	0.036	-10000	0	-0.42	3	3
RRAS	-0.014	0.055	0.19	5	-0.23	15	20
DNM1	0.032	0.041	-10000	0	-0.42	4	4
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.012	0.057	0.18	17	-0.22	17	34
lamellipodium assembly	-0.035	0.058	-10000	0	-0.23	29	29
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.016	0.068	-10000	0	-0.45	5	5
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
EPHB2	0.032	0.03	-10000	0	-0.42	2	2
EPHB3	0.018	0.085	-10000	0	-0.42	18	18
EPHB1	0.026	0.051	-10000	0	-0.42	6	6
EPHB4	0.018	0.085	-10000	0	-0.42	18	18
mol:GDP	-0.017	0.085	-10000	0	-0.33	22	22
Ephrin B/EPHB2	0.058	0.062	-10000	0	-0.22	17	17
Ephrin B/EPHB3	0.048	0.079	-10000	0	-0.23	30	30
JNK cascade	-0.013	0.062	0.29	10	-0.23	16	26
Ephrin B/EPHB1	0.056	0.066	-10000	0	-0.23	19	19
RAP1/GDP	-0.003	0.11	-10000	0	-0.28	36	36
EFNB2	0.019	0.075	-10000	0	-0.42	14	14
EFNB3	0.031	0.012	-10000	0	-10000	0	0
EFNB1	0.034	0.021	-10000	0	-0.42	1	1
Ephrin B2/EPHB1-2	0.045	0.064	-10000	0	-0.24	20	20
RAP1B	0.032	0.03	-10000	0	-0.42	2	2
RAP1A	0.03	0.05	-10000	0	-0.42	6	6
CDC42/GTP	0.036	0.09	-10000	0	-0.28	18	18
Rap1/GTP	0.015	0.069	-10000	0	-0.26	19	19
axon guidance	0.039	0.038	-10000	0	-0.25	7	7
MAPK3	0.025	0.072	0.27	1	-0.42	5	6
MAPK1	0.016	0.065	0.22	3	-0.41	5	8
Rac1/GDP	-0.014	0.1	-10000	0	-0.29	30	30
actin cytoskeleton reorganization	-0.043	0.064	-10000	0	-0.24	26	26
CDC42/GDP	-0.013	0.1	-10000	0	-0.29	33	33
PI3K	0.04	0.094	-10000	0	-0.24	45	45
EFNA5	0.029	0.046	-10000	0	-0.42	5	5
Ephrin B2/EPHB4	0.023	0.076	-10000	0	-0.27	30	30
Ephrin B/EPHB2/Intersectin/N-WASP	0.005	0.077	-10000	0	-0.32	8	8
CDC42	0.034	0.008	-10000	0	-10000	0	0
RAS family/GTP	0.008	0.065	-10000	0	-0.22	27	27
PTK2	0.11	0.23	0.55	112	-10000	0	112
MAP4K4	-0.013	0.063	0.29	10	-0.24	16	26
SRC	0.032	0.03	-10000	0	-0.42	2	2
KALRN	0.033	0.022	-10000	0	-0.42	1	1
Intersectin/N-WASP	0.044	0.048	-10000	0	-0.3	9	9
neuron projection morphogenesis	-0.028	0.078	0.26	2	-0.33	10	12
MAP2K1	0.01	0.062	0.21	1	-0.43	5	6
WASL	0.029	0.054	-10000	0	-0.42	7	7
Ephrin B1/EPHB1-2/NCK1	0.077	0.05	-10000	0	-0.23	10	10
cell migration	0.03	0.093	0.26	6	-0.44	6	12
NRAS	0.029	0.05	-10000	0	-0.42	6	6
SYNJ1	-0.012	0.052	0.19	6	-0.21	14	20
PXN	0.036	0.004	-10000	0	-10000	0	0
TF	-0.017	0.049	0.18	6	-10000	0	6
HRAS/GTP	0.042	0.074	-10000	0	-0.22	27	27
Ephrin B1/EPHB1-2	0.057	0.043	-10000	0	-0.23	9	9
cell adhesion mediated by integrin	0.011	0.057	0.23	14	-0.21	12	26
RAC1	0.035	0.006	-10000	0	-10000	0	0
mol:GTP	0.048	0.073	-10000	0	-0.23	25	25
RAC1-CDC42/GTP	-0.033	0.061	-10000	0	-0.39	5	5
RASA1	0.028	0.054	-10000	0	-0.42	7	7
RAC1-CDC42/GDP	-0.001	0.1	-10000	0	-0.3	23	23
ruffle organization	-0.03	0.074	-10000	0	-0.4	5	5
NCK1	0.034	0.022	-10000	0	-0.42	1	1
receptor internalization	-0.02	0.051	0.17	13	-0.21	17	30
Ephrin B/EPHB2/KALRN	0.073	0.072	-10000	0	-0.23	17	17
ROCK1	0.017	0.06	0.19	23	-0.23	19	42
RAS family/GDP	-0.046	0.067	-10000	0	-0.26	26	26
Rac1/GTP	0.002	0.073	-10000	0	-0.24	32	32
Ephrin B/EPHB1/Src/Paxillin	0.009	0.075	-10000	0	-0.38	7	7

×

Regulation of Androgen receptor activity

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
HDAC1	0.015	0.015	-10000	0	-0.3	1	1
SMARCC1	0.003	0.12	-10000	0	-1.1	5	5
REL	0.023	0.07	-10000	0	-0.42	12	12
HDAC7	-0.038	0.1	0.22	1	-0.32	33	34
JUN	-0.001	0.12	-10000	0	-0.42	39	39
EP300	0.033	0.022	-10000	0	-0.42	1	1
KAT2B	0	0	-10000	0	-10000	0	0
KAT5	0	0	-10000	0	-10000	0	0
MAPK14	-0.001	0.058	-10000	0	-0.31	15	15
FOXO1	0	0	-10000	0	-10000	0	0
T-DHT/AR	-0.009	0.13	-10000	0	-0.34	33	33
MAP2K6	0.011	0.08	-10000	0	-0.43	15	15
BRM/BAF57	0.047	0.024	-10000	0	-0.3	1	1
MAP2K4	0.022	0.031	-10000	0	-0.42	1	1
SMARCA2	0.034	0.022	-10000	0	-0.42	1	1
PDE9A	-0.001	0.11	-10000	0	-0.98	4	4
NCOA2	0.025	0.047	-10000	0	-0.42	5	5
CEBPA	0.024	0.07	-10000	0	-0.42	12	12
EHMT2	0.036	0.005	-10000	0	-10000	0	0
cell proliferation	0.028	0.13	0.31	20	-0.35	12	32
NR0B1	0.03	0.036	-10000	0	-0.42	3	3
EGR1	-0.037	0.16	-10000	0	-0.42	75	75
RXRs/9cRA	0.047	0.053	-10000	0	-0.23	12	12
AR/RACK1/Src	0.004	0.099	0.28	5	-0.3	13	18
AR/GR	-0.028	0.12	0.23	2	-0.24	95	97
GNB2L1	0.034	0.035	-10000	0	-0.42	3	3
PKN1	0.033	0.035	-10000	0	-0.42	3	3
RCHY1	0.022	0.075	-10000	0	-0.42	14	14
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	0.006	0.033	-10000	0	-0.31	3	3
T-DHT/AR/TIF2/CARM1	0.009	0.092	0.36	1	-0.33	9	10
SRC	-0.01	0.073	0.19	37	-0.25	16	53
NR3C1	0.022	0.078	-10000	0	-0.42	15	15
KLK3	-0.015	0.094	-10000	0	-10000	0	0
APPBP2	0.024	0.024	-10000	0	-10000	0	0
TRIM24	0.035	0.008	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.033	0.07	0.14	1	-0.29	20	21
TMPRSS2	-0.14	0.38	-10000	0	-0.95	88	88
RXRG	0.021	0.058	-10000	0	-0.42	8	8
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	0.034	0.029	-10000	0	-0.42	2	2
RXRB	0.034	0.029	-10000	0	-0.42	2	2
CARM1	0.035	0.021	-10000	0	-0.42	1	1
NR2C2	0.035	0.008	-10000	0	-10000	0	0
KLK2	0.011	0.073	0.3	3	-0.29	2	5
AR	-0.033	0.11	0.18	1	-0.24	92	93
SENP1	0.035	0.006	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
MDM2	0.033	0.008	-10000	0	-10000	0	0
SRY	0.023	0.07	-10000	0	-0.42	12	12
GATA2	0.029	0.046	-10000	0	-0.42	5	5
MYST2	0.032	0.03	-10000	0	-0.42	2	2
HOXB13	0.023	0.018	-10000	0	-10000	0	0
T-DHT/AR/RACK1/Src	0	0.1	0.29	5	-0.31	13	18
positive regulation of transcription	0.029	0.046	-10000	0	-0.42	5	5
DNAJA1	0.023	0.043	-10000	0	-0.42	3	3
proteasomal ubiquitin-dependent protein catabolic process	0.013	0.052	-10000	0	-0.29	14	14
NCOA1	0.035	0.054	-10000	0	-0.33	9	9
SPDEF	-0.045	0.18	-10000	0	-0.42	90	90
T-DHT/AR/TIF2	0.014	0.078	0.24	8	-0.3	6	14
T-DHT/AR/Hsp90	-0.032	0.07	0.14	1	-0.29	20	21
GSK3B	0.035	0.006	-10000	0	-10000	0	0
NR2C1	0.029	0.054	-10000	0	-0.42	7	7
mol:T-DHT	-0.009	0.072	0.21	29	-0.26	14	43
SIRT1	0.035	0.005	-10000	0	-10000	0	0
ZMIZ2	-0.001	0	-10000	0	-10000	0	0
POU2F1	0.016	0.055	-10000	0	-0.11	63	63
T-DHT/AR/DAX-1	-0.009	0.097	0.3	2	-0.3	21	23
CREBBP	0.033	0.011	-10000	0	-10000	0	0
SMARCE1	0.034	0.01	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.035	0.006	-10000	0	-10000	0	0
VLDLR	-0.007	0.13	-10000	0	-0.42	42	42
LRPAP1	0.035	0.007	-10000	0	-10000	0	0
NUDC	0.035	0.007	-10000	0	-10000	0	0
RELN/LRP8	0.038	0.088	-10000	0	-0.26	39	39
CaM/Ca2+	0.026	0.005	-10000	0	-10000	0	0
KATNA1	0.033	0.01	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	0.001	0.072	0.19	9	-0.23	39	48
IQGAP1/CaM	0.049	0.015	-10000	0	-10000	0	0
DAB1	0.035	0.006	-10000	0	-10000	0	0
IQGAP1	0.034	0.008	-10000	0	-10000	0	0
PLA2G7	-0.036	0.16	-10000	0	-0.42	74	74
CALM1	0.035	0.007	-10000	0	-10000	0	0
DYNLT1	0.033	0.01	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.023	0.088	-10000	0	-0.3	34	34
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0	0	-10000	0	-10000	0	0
CDK5R1	0.033	0.01	-10000	0	-10000	0	0
LIS1/Poliovirus Protein 3A	0.01	0.012	-10000	0	-0.25	1	1
CDK5R2	0.035	0.005	-10000	0	-10000	0	0
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	0.032	0.097	-10000	0	-0.26	46	46
YWHAE	0.032	0.011	-10000	0	-10000	0	0
NDEL1/14-3-3 E	0.015	0.069	0.33	1	-0.25	5	6
MAP1B	-0.007	0.06	-10000	0	-0.26	26	26
RAC1	0.015	0.007	-10000	0	-10000	0	0
p35/CDK5	0.007	0.067	0.19	7	-0.21	38	45
RELN	0.03	0.046	-10000	0	-0.42	5	5
PAFAH/LIS1	-0.011	0.1	-10000	0	-0.26	73	73
LIS1/CLIP170	0.01	0.012	-10000	0	-0.25	1	1
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	0.017	0.069	-10000	0	-0.23	2	2
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.007	0.1	-10000	0	-0.26	59	59
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.004	0.062	0.33	1	-0.26	5	6
LIS1/IQGAP1	0.033	0.014	-10000	0	-10000	0	0
RHOA	0.008	0.056	-10000	0	-0.4	9	9
PAFAH1B1	0.014	0.015	-10000	0	-0.3	1	1
PAFAH1B3	0.029	0.054	-10000	0	-0.42	7	7
PAFAH1B2	0.031	0.012	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.016	0.058	-10000	0	-0.24	3	3
NDEL1/Katanin 60/Dynein heavy chain	0.021	0.078	0.33	1	-0.25	5	6
LRP8	0	0.11	-10000	0	-0.42	34	34
NDEL1/Katanin 60	0.008	0.072	0.33	1	-0.25	5	6
P39/CDK5	0.008	0.067	0.19	7	-0.21	39	46
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.033	0.019	-10000	0	-0.26	1	1
CDK5	-0.029	0.061	0.18	8	-0.22	39	47
PPP2R5D	0.035	0.007	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.009	0.011	-10000	0	-0.21	1	1
CSNK2A1	0.034	0.008	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	0.036	0.092	-10000	0	-0.23	46	46
RELN/VLDLR	0.025	0.12	-10000	0	-0.24	79	79
CDC42	0.015	0.007	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.034	0.021	-10000	0	-0.42	1	1
HDAC2	0.032	0.023	-10000	0	-0.42	1	1
GNB1/GNG2	0.034	0.099	-10000	0	-0.26	51	51
forebrain development	-0.004	0.14	-10000	0	-0.56	17	17
GNAO1	0.03	0.014	-10000	0	-10000	0	0
SMO/beta Arrestin2	0.015	0.1	-10000	0	-0.3	46	46
SMO	-0.008	0.13	-10000	0	-0.42	46	46
ARRB2	0.033	0.011	-10000	0	-10000	0	0
GLI3/SPOP	0.003	0.15	-10000	0	-0.42	30	30
mol:GTP	0	0	-10000	0	-10000	0	0
GSK3B	0.035	0.005	-10000	0	-10000	0	0
GNAI2	0.027	0.057	-10000	0	-0.42	8	8
SIN3/HDAC complex	0.076	0.045	-10000	0	-0.23	5	5
GNAI1	0.018	0.085	-10000	0	-0.42	18	18
XPO1	0.036	0.005	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.019	0.17	-10000	0	-0.55	26	26
SAP30	0.03	0.046	-10000	0	-0.42	5	5
mol:GDP	-0.008	0.13	-10000	0	-0.42	46	46
MIM/GLI2A	0.001	0.11	-10000	0	-0.42	31	31
IFT88	0.02	0.075	-10000	0	-0.42	14	14
GNAI3	0.035	0.006	-10000	0	-10000	0	0
GLI2	0.013	0.081	0.21	1	-0.35	14	15
GLI3	-0.011	0.15	0.24	3	-0.43	30	33
CSNK1D	0.033	0.009	-10000	0	-10000	0	0
CSNK1E	0.034	0.009	-10000	0	-10000	0	0
SAP18	0.033	0.01	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.02	0.075	-10000	0	-0.42	14	14
GNG2	0.034	0.021	-10000	0	-0.42	1	1
Gi family/GTP	-0.017	0.11	-10000	0	-0.3	54	54
SIN3B	0.035	0.005	-10000	0	-10000	0	0
SIN3A	0.035	0.007	-10000	0	-10000	0	0
GLI3/Su(fu)	-0.008	0.14	-10000	0	-0.42	38	38
GLI2/Su(fu)	0.003	0.11	-10000	0	-0.4	18	18
FOXA2	-0.024	0.2	-10000	0	-0.69	39	39
neural tube patterning	-0.004	0.14	-10000	0	-0.56	17	17
SPOP	0.033	0.022	-10000	0	-0.42	1	1
Su(fu)/PIAS1	0.008	0.09	-10000	0	-0.33	16	16
GNB1	0.032	0.045	-10000	0	-0.42	5	5
CSNK1G2	0.033	0.03	-10000	0	-0.42	2	2
CSNK1G3	0.035	0.007	-10000	0	-10000	0	0
MTSS1	0.001	0.11	-10000	0	-0.42	31	31
embryonic limb morphogenesis	-0.004	0.14	-10000	0	-0.56	17	17
SUFU	-0.001	0.084	-10000	0	-0.35	16	16
LGALS3	-0.01	0.14	-10000	0	-0.42	49	49
catabolic process	0.013	0.15	-10000	0	-0.5	20	20
GLI3A/CBP	0.034	0.042	-10000	0	-0.33	6	6
KIF3A	0.027	0.061	-10000	0	-0.42	9	9
GLI1	-0.005	0.14	-10000	0	-0.57	17	17
RAB23	0.031	0.041	-10000	0	-0.42	4	4
CSNK1A1	0.035	0.005	-10000	0	-10000	0	0
IFT172	0.033	0.035	-10000	0	-0.42	3	3
RBBP7	0.033	0.029	-10000	0	-0.42	2	2
Su(fu)/Galectin3	-0.015	0.12	-10000	0	-0.29	61	61
GNAZ	0.024	0.067	-10000	0	-0.42	11	11
RBBP4	0.034	0.021	-10000	0	-0.42	1	1
CSNK1G1	0.035	0.007	-10000	0	-10000	0	0
PIAS1	0.035	0.006	-10000	0	-10000	0	0
PRKACA	0.036	0.004	-10000	0	-10000	0	0
GLI2/SPOP	0.027	0.084	-10000	0	-0.33	14	14
STK36	0.021	0.083	-10000	0	-0.42	17	17
Gi family/GNB1/GNG2/GDP	-0.021	0.12	-10000	0	-0.38	35	35
PTCH1	-0.002	0.13	-10000	0	-0.5	17	17
MIM/GLI1	0	0.13	-10000	0	-0.51	17	17
CREBBP	0.034	0.042	-10000	0	-0.33	6	6
Su(fu)/SIN3/HDAC complex	0.008	0.097	-10000	0	-0.42	16	16

×

HIF-2-alpha transcription factor network

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
MMP14	-0.003	0.27	-10000	0	-1	31	31
oxygen homeostasis	0.005	0.009	-10000	0	-10000	0	0
TCEB2	0.032	0.011	-10000	0	-10000	0	0
TCEB1	0.028	0.025	-10000	0	-0.42	1	1
VHL/Elongin B/Elongin C/HIF2A	0.053	0.11	-10000	0	-0.36	8	8
EPO	0.073	0.17	-10000	0	-0.53	14	14
FIH (dimer)	0.037	0.02	-10000	0	-10000	0	0
APEX1	0.035	0.028	-10000	0	-10000	0	0
SERPINE1	0.058	0.2	-10000	0	-0.55	25	25
FLT1	-0.037	0.27	-10000	0	-0.79	45	45
ADORA2A	0.045	0.18	-10000	0	-0.55	21	21
germ cell development	0.066	0.18	-10000	0	-0.53	18	18
SLC11A2	0.067	0.19	-10000	0	-0.55	19	19
BHLHE40	0.055	0.18	-10000	0	-0.49	24	24
HIF1AN	0.037	0.02	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.075	0.15	0.33	1	-0.38	19	20
ETS1	0.037	0.032	-10000	0	-0.42	1	1
CITED2	0.017	0.18	-10000	0	-0.84	16	16
KDR	-0.013	0.23	-10000	0	-0.79	27	27
PGK1	0.068	0.18	-10000	0	-0.55	18	18
SIRT1	0.036	0.005	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	0.11	0.22	-10000	0	-0.61	19	19
EPAS1	0.027	0.12	-10000	0	-0.33	23	23
SP1	0.034	0.038	-10000	0	-0.27	2	2
ABCG2	0.062	0.19	-10000	0	-0.58	20	20
EFNA1	0.033	0.18	-10000	0	-0.52	30	30
FXN	0.054	0.17	-10000	0	-0.53	18	18
POU5F1	0.066	0.18	-10000	0	-0.55	18	18
neuron apoptosis	-0.11	0.22	0.6	19	-10000	0	19
EP300	0.033	0.022	-10000	0	-0.42	1	1
EGLN3	-0.013	0.14	-10000	0	-0.42	52	52
EGLN2	0.033	0.045	-10000	0	-0.42	4	4
EGLN1	0.023	0.057	-10000	0	-0.42	7	7
VHL/Elongin B/Elongin C	0.053	0.035	-10000	0	-0.26	1	1
VHL	0.035	0.007	-10000	0	-10000	0	0
ARNT	0.035	0.027	-10000	0	-10000	0	0
SLC2A1	0.048	0.18	0.34	2	-0.52	22	24
TWIST1	0.041	0.2	0.34	5	-0.57	33	38
ELK1	0.039	0.032	-10000	0	-0.27	4	4
HIF2A/ARNT/Cbp/p300	0.072	0.15	0.34	1	-0.39	17	18
VEGFA	0.055	0.18	-10000	0	-0.49	24	24
CREBBP	0.032	0.011	-10000	0	-10000	0	0

×

FoxO family signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.041	0.097	-10000	0	-1.3	1	1
PLK1	0.01	0.2	-10000	0	-0.77	13	13
CDKN1B	0.044	0.16	-10000	0	-0.46	30	30
FOXO3	-0.006	0.22	-10000	0	-0.48	65	65
KAT2B	0.001	0.019	-10000	0	-0.043	65	65
FOXO1/SIRT1	0.045	0.053	-10000	0	-0.28	3	3
CAT	-0.008	0.23	-10000	0	-0.84	19	19
CTNNB1	0.024	0.067	-10000	0	-0.42	11	11
AKT1	0.027	0.05	-10000	0	-0.41	3	3
FOXO1	0.027	0.053	0.24	1	-0.28	4	5
MAPK10	0.007	0.061	0.2	9	-0.21	25	34
mol:GTP	0	0.002	-10000	0	-10000	0	0
FOXO4	0.016	0.098	0.28	1	-0.34	15	16
response to oxidative stress	0.004	0.02	-10000	0	-0.046	40	40
FOXO3A/SIRT1	0.019	0.2	-10000	0	-0.44	55	55
XPO1	0.035	0.005	-10000	0	-10000	0	0
EP300	0.035	0.023	-10000	0	-0.42	1	1
BCL2L11	0.029	0.086	-10000	0	-1.2	2	2
FOXO1/SKP2	0.042	0.049	-10000	0	-0.3	2	2
mol:GDP	0.004	0.02	-10000	0	-0.046	40	40
RAN	0.036	0.005	-10000	0	-10000	0	0
GADD45A	0.013	0.22	-10000	0	-0.77	28	28
YWHAQ	0.033	0.029	-10000	0	-0.42	2	2
FOXO1/14-3-3 family	0.039	0.12	-10000	0	-0.42	14	14
MST1	0.028	0.036	-10000	0	-10000	0	0
CSNK1D	0.033	0.009	-10000	0	-10000	0	0
CSNK1E	0.034	0.009	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.008	0.13	-10000	0	-0.4	26	26
YWHAB	0.034	0.009	-10000	0	-10000	0	0
MAPK8	0.017	0.044	0.2	10	-0.21	7	17
MAPK9	0.008	0.059	0.2	8	-0.22	23	31
YWHAG	0.035	0.005	-10000	0	-10000	0	0
YWHAE	0.032	0.011	-10000	0	-10000	0	0
YWHAZ	0.026	0.016	-10000	0	-10000	0	0
SIRT1	0.036	0.02	-10000	0	-10000	0	0
SOD2	0.031	0.16	-10000	0	-0.62	12	12
RBL2	-0.079	0.32	-10000	0	-0.74	75	75
RAL/GDP	0.045	0.038	-10000	0	-0.25	4	4
CHUK	0.018	0.075	-10000	0	-0.42	11	11
Ran/GTP	0.026	0.01	-10000	0	-10000	0	0
CSNK1G2	0.033	0.03	-10000	0	-0.42	2	2
RAL/GTP	0.046	0.038	-10000	0	-0.22	4	4
CSNK1G1	0.035	0.007	-10000	0	-10000	0	0
FASLG	-0.092	0.4	-10000	0	-1.4	45	45
SKP2	0.034	0.009	-10000	0	-10000	0	0
USP7	0.032	0.012	-10000	0	-10000	0	0
IKBKB	0.023	0.035	-10000	0	-10000	0	0
CCNB1	-0.051	0.33	-10000	0	-1	42	42
FOXO1-3a-4/beta catenin	0.038	0.16	0.42	1	-0.41	27	28
proteasomal ubiquitin-dependent protein catabolic process	0.042	0.049	-10000	0	-0.3	2	2
CSNK1A1	0.035	0.005	-10000	0	-10000	0	0
SGK1	0.001	0.019	-10000	0	-0.043	65	65
CSNK1G3	0.035	0.007	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.048	0.013	-10000	0	-10000	0	0
ZFAND5	0.017	0.085	0.26	1	-0.28	15	16
SFN	0.011	0.099	-10000	0	-0.42	25	25
CDK2	0.036	0.03	-10000	0	-0.42	2	2
FOXO3A/14-3-3	0.015	0.12	-10000	0	-0.38	24	24
CREBBP	0.035	0.013	-10000	0	-10000	0	0
FBXO32	0.02	0.31	0.44	2	-1.1	23	25
BCL6	-0.008	0.27	-10000	0	-1.1	22	22
RALB	0.032	0.041	-10000	0	-0.42	4	4
RALA	0.035	0.007	-10000	0	-10000	0	0
YWHAH	0.031	0.036	-10000	0	-0.42	3	3

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.035	0.073	-10000	0	-0.32	20	20
AKT1	0.011	0.12	0.32	1	-0.41	18	19
PTK2B	-0.001	0.091	0.36	1	-0.51	8	9
VEGFR2 homodimer/Frs2	0.029	0.076	-10000	0	-0.39	11	11
CAV1	0.028	0.05	-10000	0	-0.42	6	6
CALM1	0.035	0.007	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.026	0.081	-10000	0	-0.38	11	11
endothelial cell proliferation	0.036	0.12	0.3	16	-0.45	8	24
mol:Ca2+	0.005	0.096	-10000	0	-0.32	29	29
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.044	0.084	-10000	0	-0.48	7	7
RP11-342D11.1	-0.011	0.097	-10000	0	-0.3	35	35
CDH5	0.027	0.037	-10000	0	-0.42	3	3
VEGFA homodimer	0.037	0.086	-10000	0	-0.24	43	43
SHC1	0.027	0.025	-10000	0	-0.42	1	1
SHC2	-0.026	0.16	-10000	0	-0.42	67	67
HRAS/GDP	0.019	0.091	-10000	0	-0.42	8	8
SH2D2A	-0.001	0.1	-10000	0	-0.42	29	29
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.037	0.11	-10000	0	-0.46	12	12
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.005	0.097	-10000	0	-0.28	38	38
VEGFR1 homodimer	0.026	0.054	-10000	0	-0.42	7	7
SHC/GRB2/SOS1	0.041	0.11	-10000	0	-0.46	8	8
GRB10	-0.004	0.12	-10000	0	-0.51	20	20
PTPN11	0.036	0.004	-10000	0	-10000	0	0
GRB2	0.033	0.01	-10000	0	-10000	0	0
PAK1	0.014	0.085	-10000	0	-0.42	18	18
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.042	0.1	-10000	0	-0.46	10	10
HRAS	0.032	0.036	-10000	0	-0.42	3	3
VEGF/Rho/ROCK1/Integrin Complex	0.004	0.1	-10000	0	-0.36	25	25
HIF1A	-0.007	0.13	-10000	0	-0.42	45	45
FRS2	0.033	0.022	-10000	0	-0.42	1	1
oxygen and reactive oxygen species metabolic process	0.042	0.083	-10000	0	-0.47	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.035	0.006	-10000	0	-10000	0	0
Nck/Pak	0.031	0.069	-10000	0	-0.3	19	19
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.022	0.092	-10000	0	-0.38	15	15
mol:GDP	0.029	0.097	-10000	0	-0.42	9	9
mol:NADP	0.021	0.1	-10000	0	-0.43	10	10
eNOS/Hsp90	0.019	0.096	-10000	0	-0.41	10	10
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
mol:IP3	0.005	0.097	-10000	0	-0.32	29	29
HIF1A/ARNT	0.02	0.099	-10000	0	-0.3	43	43
SHB	0.03	0.046	-10000	0	-0.42	5	5
VEGFA	-0.002	0.016	-10000	0	-10000	0	0
VEGFC	0.022	0.073	-10000	0	-0.42	13	13
FAK1/Vinculin	0.015	0.12	0.36	1	-0.5	11	12
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.026	0.061	-10000	0	-0.42	9	9
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.033	0.1	-10000	0	-0.31	27	27
PTPN6	0.032	0.03	-10000	0	-0.42	2	2
EPAS1	0.029	0.071	-10000	0	-0.39	12	12
mol:L-citrulline	0.021	0.1	-10000	0	-0.43	10	10
ITGAV	0.021	0.08	-10000	0	-0.42	16	16
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.041	0.08	-10000	0	-0.47	6	6
VEGFR2 homodimer/VEGFA homodimer	0.022	0.12	-10000	0	-0.33	36	36
VEGFR2/3 heterodimer	0.03	0.076	-10000	0	-0.4	11	11
VEGFB	0.034	0.021	-10000	0	-0.42	1	1
MAPK11	-0.015	0.11	0.26	2	-0.44	16	18
VEGFR2 homodimer	0.012	0.081	-10000	0	-0.46	11	11
FLT1	0.026	0.054	-10000	0	-0.42	7	7
NEDD4	0.02	0.074	-10000	0	-0.42	12	12
MAPK3	0.005	0.095	0.26	10	-0.39	10	20
MAPK1	-0.001	0.095	0.25	6	-0.41	10	16
VEGFA145/NRP2	0.023	0.024	-10000	0	-0.33	1	1
VEGFR1/2 heterodimer	0.024	0.085	-10000	0	-0.37	16	16
KDR	0.012	0.082	-10000	0	-0.46	11	11
VEGFA165/NRP1/VEGFR2 homodimer	0.023	0.11	-10000	0	-0.31	34	34
SRC	0.032	0.03	-10000	0	-0.42	2	2
platelet activating factor biosynthetic process	0.004	0.099	0.26	9	-0.42	10	19
PI3K	0.006	0.12	-10000	0	-0.5	14	14
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.026	0.082	-10000	0	-0.38	12	12
FES	0	0.11	-10000	0	-0.32	33	33
GAB1	0.015	0.12	-10000	0	-0.41	24	24
VEGFR2 homodimer/VEGFA homodimer/Src	0.026	0.079	-10000	0	-0.36	13	13
CTNNB1	0.024	0.067	-10000	0	-0.42	11	11
SOS1	0.034	0.021	-10000	0	-0.42	1	1
ARNT	0.035	0.006	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.032	0.11	-10000	0	-0.42	12	12
VEGFR2 homodimer/VEGFA homodimer/Yes	0.023	0.087	-10000	0	-0.34	17	17
PI3K/GAB1	0.021	0.13	0.28	1	-0.43	20	21
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.042	0.096	-10000	0	-0.43	7	7
PRKACA	0.036	0.004	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.041	0.095	-10000	0	-0.35	20	20
HSP90AA1	0	0	-10000	0	-10000	0	0
CDC42	0.002	0.1	-10000	0	-0.32	32	32
actin cytoskeleton reorganization	0.005	0.097	-10000	0	-0.28	38	38
PTK2	-0.006	0.1	-10000	0	-0.52	12	12
EDG1	-0.009	0.14	-10000	0	-0.53	27	27
mol:DAG	0.005	0.097	-10000	0	-0.32	29	29
CaM/Ca2+	0.02	0.095	-10000	0	-0.3	26	26
MAP2K3	-0.012	0.099	0.21	1	-0.47	11	12
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.015	0.13	-10000	0	-0.5	21	21
PLCG1	0.005	0.098	-10000	0	-0.32	29	29
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.04	0.086	-10000	0	-0.3	18	18
IQGAP1	0.034	0.008	-10000	0	-10000	0	0
YES1	0.029	0.05	-10000	0	-0.42	6	6
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.028	0.082	-10000	0	-0.4	11	11
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.026	0.081	-10000	0	-0.4	11	11
cell migration	0.017	0.1	0.31	2	-0.49	9	11
mol:PI-3-4-5-P3	0.007	0.12	-10000	0	-0.46	14	14
FYN	0.027	0.05	-10000	0	-0.42	6	6
VEGFB/NRP1	0.008	0.1	-10000	0	-0.3	34	34
mol:NO	0.021	0.1	-10000	0	-0.43	10	10
PXN	0.036	0.004	-10000	0	-10000	0	0
HRAS/GTP	0.003	0.083	-10000	0	-0.4	9	9
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.004	0.13	-10000	0	-0.5	21	21
VHL	0.035	0.007	-10000	0	-10000	0	0
ITGB3	0.029	0.046	-10000	0	-0.42	5	5
NOS3	0.02	0.11	-10000	0	-0.49	10	10
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.006	0.12	-10000	0	-0.26	73	73
RAC1	0.035	0.006	-10000	0	-10000	0	0
PRKCA	-0.005	0.083	0.21	1	-0.41	9	10
PRKCB	-0.008	0.088	-10000	0	-0.44	10	10
VCL	0.035	0.021	-10000	0	-0.42	1	1
VEGFA165/NRP1	-0.007	0.096	-10000	0	-0.3	35	35
VEGFR1/2 heterodimer/VEGFA homodimer	0.021	0.09	-10000	0	-0.36	16	16
VEGFA165/NRP2	0.023	0.024	-10000	0	-0.33	1	1
MAPKKK cascade	0.033	0.13	0.36	7	-0.43	17	24
NRP2	0.034	0.021	-10000	0	-0.42	1	1
VEGFC homodimer	0.022	0.073	-10000	0	-0.42	13	13
NCK1	0.034	0.022	-10000	0	-0.42	1	1
ROCK1	0.035	0.005	-10000	0	-10000	0	0
FAK1/Paxillin	0.016	0.12	0.36	1	-0.5	12	13
MAP3K13	0	0.11	-10000	0	-0.32	35	35
PDPK1	-0.003	0.099	0.25	2	-0.4	15	17

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.031	0.013	-10000	0	-10000	0	0
ELF1	0.013	0.099	-10000	0	-0.35	34	34
CCNA2	0.009	0.1	-10000	0	-0.42	28	28
PIK3CA	0.034	0.022	-10000	0	-0.42	1	1
JAK3	0.036	0.005	-10000	0	-10000	0	0
PIK3R1	0.019	0.083	-10000	0	-0.42	17	17
JAK1	0.032	0.036	-10000	0	-0.42	3	3
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.021	0.14	-10000	0	-0.41	24	24
SHC1	0.028	0.025	-10000	0	-0.42	1	1
SP1	0.033	0.069	-10000	0	-0.36	14	14
IL2RA	-0.025	0.17	-10000	0	-0.6	37	37
IL2RB	0.012	0.095	-10000	0	-0.42	23	23
SOS1	0.035	0.021	-10000	0	-0.42	1	1
IL2RG	0.031	0.041	-10000	0	-0.42	4	4
G1/S transition of mitotic cell cycle	-0.018	0.19	-10000	0	-0.53	43	43
PTPN11	0.036	0.004	-10000	0	-10000	0	0
CCND2	0.005	0.11	-10000	0	-0.68	13	13
LCK	-0.017	0.14	-10000	0	-0.42	54	54
GRB2	0.033	0.011	-10000	0	-10000	0	0
IL2	0.033	0.036	-10000	0	-0.42	3	3
CDK6	0.025	0.054	-10000	0	-0.42	7	7
CCND3	0.025	0.13	0.4	1	-0.51	3	4

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.03	0.041	-10000	0	-0.42	4	4
RAS family/GTP/Tiam1	0.011	0.067	-10000	0	-0.27	19	19
NT3 (dimer)/TRKC	0.039	0.044	-10000	0	-0.3	7	7
NT3 (dimer)/TRKB	0.046	0.07	-10000	0	-0.26	21	21
SHC/Grb2/SOS1/GAB1/PI3K	0.014	0.052	-10000	0	-0.24	1	1
RAPGEF1	0.036	0.004	-10000	0	-10000	0	0
BDNF	0.03	0.024	-10000	0	-0.42	1	1
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
DYNLT1	0.033	0.01	-10000	0	-10000	0	0
NTRK1	0.025	0.032	-10000	0	-0.42	2	2
NTRK2	0.019	0.078	-10000	0	-0.42	15	15
NTRK3	0.031	0.012	-10000	0	-10000	0	0
NT-4/5 (dimer)/TRKB	0.033	0.055	-10000	0	-0.25	17	17
neuron apoptosis	0.003	0.14	0.31	56	-0.25	2	58
SHC 2-3/Grb2	-0.004	0.15	0.26	2	-0.33	56	58
SHC1	0.027	0.025	-10000	0	-0.42	1	1
SHC2	-0.036	0.18	0.24	2	-0.43	79	81
SHC3	0.019	0.11	0.24	3	-0.41	20	23
STAT3 (dimer)	-0.017	0.13	-10000	0	-0.34	70	70
NT3 (dimer)/TRKA	0.042	0.054	-10000	0	-0.26	10	10
RIN/GDP	0.068	0.085	0.25	26	-0.26	6	32
GIPC1	0.033	0.035	-10000	0	-0.42	3	3
KRAS	0.027	0.057	-10000	0	-0.42	8	8
DNAJA3	0.007	0.055	0.21	18	-0.24	5	23
RIN/GTP	0.024	0.021	-10000	0	-0.3	2	2
CCND1	-0.079	0.24	-10000	0	-0.69	68	68
MAGED1	0.015	0.095	-10000	0	-0.42	23	23
PTPN11	0.036	0.004	-10000	0	-10000	0	0
RICS	0.023	0.061	-10000	0	-0.42	9	9
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.051	0.036	-10000	0	-0.26	1	1
GRB2	0.033	0.01	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.032	0.033	-10000	0	-0.25	4	4
TRKA/NEDD4-2	0.021	0.079	-10000	0	-0.3	26	26
ELMO1	0.035	0.006	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0.041	0.039	-10000	0	-0.25	8	8
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.032	0.036	-10000	0	-0.42	3	3
DOCK1	0.027	0.057	-10000	0	-0.42	8	8
GAB2	0.031	0.013	-10000	0	-10000	0	0
RIT2	0.033	0.03	-10000	0	-0.42	2	2
RIT1	0.026	0.032	-10000	0	-0.42	2	2
FRS2	0.033	0.022	-10000	0	-0.42	1	1
DNM1	0.032	0.041	-10000	0	-0.42	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.031	0.023	-10000	0	-0.42	1	1
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.043	0.067	0.23	20	-0.23	5	25
mol:GDP	0.071	0.11	0.29	28	-0.39	6	34
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.026	0.005	-10000	0	-10000	0	0
RIT1/GDP	0.039	0.07	0.24	7	-0.25	5	12
TIAM1	0.028	0.057	-10000	0	-0.42	8	8
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
BDNF (dimer)/TRKB	0.052	0.064	-10000	0	-0.26	19	19
KIDINS220/CRKL/C3G	0.047	0.034	-10000	0	-0.3	4	4
SHC/RasGAP	0.035	0.046	-10000	0	-0.3	7	7
FRS2 family/SHP2	0.066	0.025	-10000	0	-0.26	1	1
SHC/GRB2/SOS1/GAB1	0.06	0.054	-10000	0	-0.24	6	6
RIT1/GTP	0.02	0.023	-10000	0	-0.3	2	2
NT3 (dimer)	0.024	0.054	-10000	0	-0.42	7	7
RAP1/GDP	0.048	0.067	0.18	18	-0.23	6	24
KIDINS220/CRKL	0.03	0.041	-10000	0	-0.42	4	4
BDNF (dimer)	0.03	0.024	-10000	0	-0.42	1	1
ubiquitin-dependent protein catabolic process	0.019	0.067	-10000	0	-0.25	26	26
Schwann cell development	-0.007	0.013	-10000	0	-10000	0	0
EHD4	0.031	0.041	-10000	0	-0.42	4	4
FRS2 family/GRB2/SOS1	0.076	0.041	-10000	0	-0.44	1	1
FRS2 family/SHP2/CRK family/C3G/GAB2	0.024	0.06	-10000	0	-0.25	5	5
RAP1B	0.032	0.03	-10000	0	-0.42	2	2
RAP1A	0.03	0.05	-10000	0	-0.42	6	6
CDC42/GTP	0.043	0.069	-10000	0	-0.22	25	25
ABL1	0.035	0.005	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.047	0.023	-10000	0	-0.3	1	1
Rap1/GTP	0.022	0.091	-10000	0	-0.4	10	10
STAT3	-0.017	0.13	-10000	0	-0.34	70	70
axon guidance	0.026	0.06	-10000	0	-0.21	26	26
MAPK3	0.051	0.078	0.19	106	-0.23	5	111
MAPK1	0.052	0.078	0.19	108	-0.23	5	113
CDC42/GDP	0.069	0.086	0.24	31	-0.27	5	36
NTF3	0.024	0.054	-10000	0	-0.42	7	7
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.034	0.031	-10000	0	-0.25	3	3
PI3K	0.035	0.067	-10000	0	-0.3	18	18
FRS3	0.035	0.007	-10000	0	-10000	0	0
FAIM	0.034	0.021	-10000	0	-0.42	1	1
GAB1	0.027	0.061	-10000	0	-0.42	9	9
RASGRF1	0.007	0.06	0.22	18	-0.22	8	26
SOS1	0.034	0.021	-10000	0	-0.42	1	1
MCF2L	0.013	0.035	-10000	0	-0.26	8	8
RGS19	0.03	0.031	-10000	0	-0.42	2	2
CDC42	0.034	0.008	-10000	0	-10000	0	0
RAS family/GTP	0.067	0.1	0.32	4	-0.39	6	10
Rac1/GDP	0.068	0.086	0.24	30	-0.27	5	35
NGF (dimer)/TRKA/GRIT	0.026	0.047	-10000	0	-0.25	11	11
neuron projection morphogenesis	-0.001	0.19	0.44	2	-0.84	16	18
NGF (dimer)/TRKA/NEDD4-2	0.02	0.067	-10000	0	-0.25	26	26
MAP2K1	0.037	0.1	0.2	129	-0.22	6	135
NGFR	0.03	0.036	-10000	0	-0.42	3	3
NGF (dimer)/TRKA/GIPC/GAIP	0.017	0.044	-10000	0	-0.3	7	7
RAS family/GTP/PI3K	0.011	0.067	-10000	0	-0.24	29	29
FRS2 family/SHP2/GRB2/SOS1	0.088	0.047	-10000	0	-0.42	1	1
NRAS	0.029	0.05	-10000	0	-0.42	6	6
GRB2/SOS1	0.047	0.023	-10000	0	-0.3	1	1
PRKCI	0.024	0.067	-10000	0	-0.42	11	11
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.035	0.006	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	0.005	0.061	-10000	0	-0.42	6	6
RASA1	0.028	0.054	-10000	0	-0.42	7	7
TRKA/c-Abl	0.038	0.032	-10000	0	-0.3	2	2
SQSTM1	0.034	0.021	-10000	0	-0.42	1	1
BDNF (dimer)/TRKB/GIPC	0.067	0.065	-10000	0	-0.23	18	18
NGF (dimer)/TRKA/p62/Atypical PKCs	0.039	0.048	-10000	0	-0.22	11	11
MATK	0.031	0.031	-10000	0	-0.42	2	2
NEDD4L	0.006	0.11	-10000	0	-0.42	31	31
RAS family/GDP	-0.012	0.036	-10000	0	-0.18	10	10
NGF (dimer)/TRKA	0.01	0.056	0.22	16	-0.25	5	21
Rac1/GTP	-0.001	0.052	-10000	0	-0.22	14	14
FRS2 family/SHP2/CRK family	0.081	0.055	-10000	0	-0.22	6	6

×

LPA4-mediated signaling events

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
ADCY4	-0.015	0.037	-10000	0	-0.25	12	12
ADCY5	-0.013	0.038	-10000	0	-0.25	12	12
ADCY6	-0.011	0.024	-10000	0	-0.25	5	5
ADCY7	-0.01	0.025	-10000	0	-0.25	5	5
ADCY1	-0.011	0.022	-10000	0	-0.25	4	4
ADCY2	-0.028	0.069	-10000	0	-0.25	43	43
ADCY3	-0.014	0.036	-10000	0	-0.25	11	11
ADCY8	-0.008	0.019	-10000	0	-0.25	3	3
PRKCE	0.006	0.03	-10000	0	-0.3	5	5
ADCY9	-0.016	0.046	-10000	0	-0.27	16	16
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	0.022	0.084	0.21	35	-0.28	5	40

×

Sphingosine 1-phosphate (S1P) 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
SPHK2	0.034	0.021	-10000	0	-0.42	1	1
SPHK1	0.005	0.11	-10000	0	-0.42	30	30
GNAI2	0.027	0.057	-10000	0	-0.42	8	8
mol:S1P	0.001	0.066	-10000	0	-0.27	26	26
GNAO1	0.03	0.014	-10000	0	-10000	0	0
mol:Sphinganine-1-P	-0.004	0.075	-10000	0	-0.3	30	30
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.04	0.07	-10000	0	-0.22	24	24
GNAI3	0.035	0.006	-10000	0	-10000	0	0
G12/G13	0.043	0.036	-10000	0	-0.3	4	4
S1PR3	0	0	-10000	0	-10000	0	0
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	0.011	0.099	-10000	0	-0.42	25	25
S1P1/S1P	0.022	0.091	0.18	3	-0.25	40	43
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
GNAI1	0.017	0.085	-10000	0	-0.42	18	18
S1P/S1P5/G12	0.029	0.067	-10000	0	-0.22	26	26
S1P/S1P3/Gq	-0.003	0.095	-10000	0	-0.25	53	53
S1P/S1P4/Gi	0.002	0.095	-10000	0	-0.33	24	24
GNAQ	0	0	-10000	0	-10000	0	0
GNAZ	0.024	0.067	-10000	0	-0.42	11	11
GNA14	-0.01	0.13	-10000	0	-0.42	44	44
GNA15	0.029	0.046	-10000	0	-0.42	5	5
GNA12	0.035	0.006	-10000	0	-10000	0	0
GNA13	0.028	0.042	-10000	0	-0.42	4	4
GNA11	0.032	0.036	-10000	0	-0.42	3	3
ABCC1	0.029	0.042	-10000	0	-0.42	4	4

×

Aurora A 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
Aurora A/GADD45A	0.032	0.056	-10000	0	-0.24	15	15
BIRC5	-0.003	0.12	-10000	0	-0.42	38	38
NFKBIA	0.013	0.052	0.25	15	-0.25	2	17
CPEB1	0.03	0.041	-10000	0	-0.42	4	4
AKT1	0.009	0.044	0.25	7	-0.25	3	10
NDEL1	0.032	0.011	-10000	0	-10000	0	0
Aurora A/BRCA1	0.028	0.047	-10000	0	-0.23	12	12
NDEL1/TACC3	0.041	0.049	-10000	0	-0.19	6	6
GADD45A	0.019	0.08	-10000	0	-0.42	16	16
GSK3B	0.038	0.016	-10000	0	-10000	0	0
PAK1/Aurora A	0.027	0.06	-10000	0	-0.24	18	18
MDM2	0.034	0.009	-10000	0	-10000	0	0
JUB	0.002	0.12	-10000	0	-0.42	36	36
TPX2	-0.008	0.084	-10000	0	-0.3	38	38
TP53	-0.005	0.093	-10000	0	-0.23	67	67
DLG7	-0.011	0.06	0.25	5	-0.23	11	16
AURKAIP1	0	0	-10000	0	-10000	0	0
ARHGEF7	0.032	0.011	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.044	0.052	-10000	0	-0.21	6	6
G2/M transition of mitotic cell cycle	0.027	0.047	-10000	0	-0.23	12	12
AURKA	0.023	0.035	-10000	0	-10000	0	0
AURKB	0	0.062	-10000	0	-0.18	43	43
CDC25B	0.013	0.048	-10000	0	-0.29	5	5
G2/M transition checkpoint	0.017	0.07	-10000	0	-0.22	36	36
mRNA polyadenylation	0.033	0.033	-10000	0	-0.2	4	4
Aurora A/CPEB	0.033	0.033	-10000	0	-0.2	4	4
Aurora A/TACC1/TRAP/chTOG	0.05	0.076	-10000	0	-0.24	22	22
BRCA1	0.021	0.07	-10000	0	-0.42	12	12
centrosome duplication	0.027	0.06	-10000	0	-0.24	18	18
regulation of centrosome cycle	0.04	0.048	-10000	0	-0.19	6	6
spindle assembly	0.048	0.075	-10000	0	-0.23	22	22
TDRD7	0.026	0.064	-10000	0	-0.42	10	10
Aurora A/RasGAP/Survivin	0.033	0.081	-10000	0	-0.21	28	28
CENPA	-0.006	0.084	-10000	0	-0.28	43	43
Aurora A/PP2A	0.041	0.029	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	-0.001	0.048	0.19	1	-0.32	2	3
negative regulation of DNA binding	-0.006	0.097	-10000	0	-0.24	68	68
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.045	0.024	-10000	0	-0.3	1	1
RASA1	0.028	0.054	-10000	0	-0.42	7	7
Ajuba/Aurora A	0.018	0.07	-10000	0	-0.22	36	36
mitotic prometaphase	0.004	0.024	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.035	-10000	0	-10000	0	0
TACC1	0.012	0.087	-10000	0	-0.42	19	19
TACC3	0.017	0.087	-10000	0	-0.42	19	19
Aurora A/Antizyme1	0.036	0.025	-10000	0	-10000	0	0
Aurora A/RasGAP	0.037	0.044	-10000	0	-0.25	7	7
OAZ1	0.035	0.006	-10000	0	-10000	0	0
RAN	0.035	0.005	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.038	0.016	-10000	0	-10000	0	0
GIT1	0.033	0.022	-10000	0	-0.42	1	1
GIT1/beta-PIX/PAK1	0.043	0.068	-10000	0	-0.27	18	18
Importin alpha/Importin beta/TPX2	-0.008	0.084	-10000	0	-0.3	38	38
PPP2R5D	0.035	0.007	-10000	0	-10000	0	0
Aurora A/TPX2	0.007	0.052	-10000	0	-0.2	8	8
PAK1	0.014	0.085	-10000	0	-0.42	18	18
CKAP5	0.035	0.006	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	0.014	0.096	-10000	0	-1	4	4
MKNK1	0.035	0.006	-10000	0	-10000	0	0
MAPK14	0.031	0.049	-10000	0	-0.3	4	4
ATF2/c-Jun	-0.022	0.16	-10000	0	-0.55	40	40
MAPK11	0.03	0.047	-10000	0	-0.3	4	4
MITF	0.021	0.051	-10000	0	-0.36	6	6
MAPKAPK5	0.023	0.043	-10000	0	-0.33	4	4
KRT8	0.01	0.075	-10000	0	-0.29	25	25
MAPKAPK3	0.034	0.008	-10000	0	-10000	0	0
MAPKAPK2	0.025	0.043	-10000	0	-0.42	4	4
p38alpha-beta/CK2	0.041	0.064	-10000	0	-0.43	4	4
CEBPB	0.018	0.053	-10000	0	-0.32	9	9
SLC9A1	0.023	0.042	-10000	0	-0.33	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.016	0.072	0.23	1	-0.3	11	12
p38alpha-beta/MNK1	0.056	0.06	-10000	0	-0.36	3	3
JUN	-0.025	0.16	-10000	0	-0.55	40	40
PPARGC1A	0.016	0.068	-10000	0	-0.34	13	13
USF1	0.012	0.057	-10000	0	-0.29	13	13
RAB5/GDP/GDI1	0.024	0.053	-10000	0	-0.23	5	5
NOS2	0.016	0.042	-10000	0	-0.34	4	4
DDIT3	0.023	0.045	-10000	0	-0.32	5	5
RAB5A	0.035	0.006	-10000	0	-10000	0	0
HSPB1	-0.012	0.086	0.28	3	-0.26	48	51
p38alpha-beta/HBP1	0.053	0.067	-10000	0	-0.32	7	7
CREB1	0.014	0.062	-10000	0	-0.3	10	10
RAB5/GDP	0.026	0.004	-10000	0	-10000	0	0
EIF4E	0.015	0.044	0.24	2	-0.32	3	5
RPS6KA4	0.022	0.048	-10000	0	-0.36	5	5
PLA2G4A	0	0.066	-10000	0	-0.28	21	21
GDI1	0.023	0.045	-10000	0	-0.32	5	5
TP53	-0.001	0.062	-10000	0	-0.33	9	9
RPS6KA5	0.009	0.075	-10000	0	-0.28	26	26
ESR1	-0.054	0.14	-10000	0	-0.28	130	130
HBP1	0.032	0.036	-10000	0	-0.42	3	3
MEF2C	0.01	0.081	-10000	0	-0.33	23	23
MEF2A	0.022	0.044	-10000	0	-0.32	5	5
EIF4EBP1	0.009	0.066	-10000	0	-0.31	12	12
KRT19	-0.003	0.092	-10000	0	-0.28	43	43
ELK4	0.018	0.041	-10000	0	-0.31	4	4
ATF6	0.017	0.043	-10000	0	-0.32	5	5
ATF1	0.015	0.063	-10000	0	-0.3	10	10
p38alpha-beta/MAPKAPK2	0.042	0.069	-10000	0	-0.36	6	6
p38alpha-beta/MAPKAPK3	0.054	0.062	-10000	0	-0.35	4	4

×

Regulation of p38-alpha and p38-beta

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.041	0.018	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.035	0.007	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.017	0.078	-10000	0	-0.42	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.029	0.024	-10000	0	-0.42	1	1
RAC1-CDC42/GTP/PAK family	0.002	0.064	-10000	0	-0.21	38	38
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.029	0.05	-10000	0	-0.42	6	6
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.031	0.012	-10000	0	-10000	0	0
FYN	0.027	0.05	-10000	0	-0.42	6	6
MAP3K12	0.036	0.004	-10000	0	-10000	0	0
FGR	0.034	0.008	-10000	0	-10000	0	0
p38 alpha/TAB1	-0.004	0.14	0.2	1	-0.34	49	50
PRKG1	0.035	0.005	-10000	0	-10000	0	0
DUSP8	0.02	0.08	-10000	0	-0.42	16	16
PGK/cGMP/p38 alpha	-0.008	0.14	-10000	0	-0.35	44	44
apoptosis	-0.005	0.13	0.2	1	-0.33	49	50
RAL/GTP	0.044	0.028	-10000	0	-0.25	4	4
LYN	0.03	0.014	-10000	0	-10000	0	0
DUSP1	0.001	0.12	-10000	0	-0.42	35	35
PAK1	0.014	0.085	-10000	0	-0.42	18	18
SRC	0.032	0.03	-10000	0	-0.42	2	2
RAC1/OSM/MEKK3/MKK3	0.072	0.04	-10000	0	-0.24	1	1
TRAF6	0.034	0.021	-10000	0	-0.42	1	1
RAC1	0.035	0.006	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.035	0.006	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.045	0.013	-10000	0	-10000	0	0
MAPK11	-0.014	0.14	0.23	2	-0.39	37	39
BLK	0.021	0.038	-10000	0	-0.42	3	3
HCK	0.017	0.087	-10000	0	-0.42	19	19
MAP2K3	0.032	0.023	-10000	0	-0.42	1	1
DUSP16	0.029	0.046	-10000	0	-0.42	5	5
DUSP10	0.012	0.082	-10000	0	-0.42	17	17
TRAF6/MEKK3	0.039	0.02	-10000	0	-0.23	1	1
MAP3K7IP1	0.034	0.009	-10000	0	-10000	0	0
MAPK14	-0.017	0.14	0.2	5	-0.36	53	58
positive regulation of innate immune response	-0.018	0.17	0.26	2	-0.42	48	50
LCK	-0.018	0.14	-10000	0	-0.42	54	54
p38alpha-beta/MKP7	-0.006	0.16	0.27	2	-0.4	47	49
p38alpha-beta/MKP5	-0.012	0.16	0.27	1	-0.41	45	46
PGK/cGMP	0.026	0.004	-10000	0	-10000	0	0
PAK2	0.036	0	-10000	0	-10000	0	0
p38alpha-beta/MKP1	-0.018	0.17	0.27	2	-0.42	51	53
CDC42	0.034	0.008	-10000	0	-10000	0	0
RALB	0.032	0.041	-10000	0	-0.42	4	4
RALA	0.035	0.007	-10000	0	-10000	0	0
PAK3	0.016	0.083	-10000	0	-0.42	17	17

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.017	0.085	-9999	-0.42	18	18
GPC2	0	0	-9999	-10000	0	0
GPC2/Midkine	0.013	0.06	-9999	-0.3	18	18
neuron projection morphogenesis	0.013	0.06	-9999	-0.3	18	18

×

p38 MAPK signaling pathway

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
TRAF6/ASK1	0.014	0.057	-10000	0	-0.2	26	26
TRAF2/ASK1	0.029	0.065	-10000	0	-0.25	24	24
ATM	0.031	0.013	-10000	0	-10000	0	0
MAP2K3	-0.05	0.16	0.28	2	-0.4	59	61
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.04	0.14	0.29	1	-0.35	53	54
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.026	0.064	-10000	0	-0.42	10	10
TXN	0.009	0.002	-10000	0	-10000	0	0
CALM1	0.035	0.007	-10000	0	-10000	0	0
GADD45A	0.019	0.08	-10000	0	-0.42	16	16
GADD45B	0.024	0.067	-10000	0	-0.42	11	11
MAP3K1	0.01	0.099	-10000	0	-0.42	25	25
MAP3K6	0.034	0.022	-10000	0	-0.42	1	1
MAP3K7	0.033	0.01	-10000	0	-10000	0	0
MAP3K4	0.033	0.01	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.032	0.074	-10000	0	-0.3	23	23
TAK1/TAB family	0.014	0.037	-10000	0	-0.25	6	6
RAC1/OSM/MEKK3	0.058	0.026	-10000	0	-10000	0	0
TRAF2	0.033	0.029	-10000	0	-0.42	2	2
RAC1/OSM/MEKK3/MKK3	-0.017	0.13	-10000	0	-0.32	46	46
TRAF6	0.015	0.024	-10000	0	-0.29	3	3
RAC1	0.035	0.006	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.014	0.13	-10000	0	-0.42	49	49
CCM2	0.035	0.006	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.013	0.088	-10000	0	-0.25	49	49
MAPK11	0.033	0.01	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.017	0.1	-10000	0	-0.23	69	69
OSM/MEKK3	0.045	0.019	-10000	0	-10000	0	0
TAOK1	0.012	0.031	-10000	0	-0.29	5	5
TAOK2	0.015	0.008	-10000	0	-10000	0	0
TAOK3	0.015	0.015	-10000	0	-0.29	1	1
MAP3K7IP1	0.034	0.009	-10000	0	-10000	0	0
MAPK14	0.035	0.005	-10000	0	-10000	0	0
MAP3K7IP2	0.031	0.03	-10000	0	-0.42	2	2
MAP3K5	0.013	0.093	-10000	0	-0.42	22	22
MAP3K10	0.022	0.075	-10000	0	-0.42	14	14
MAP3K3	0.031	0.012	-10000	0	-10000	0	0
TRX/ASK1	0.017	0.059	-10000	0	-0.21	29	29
GADD45/MTK1/MTK1	0.054	0.082	-10000	0	-0.23	33	33

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.045	0.038	-10000	0	-0.3	5	5
CRKL	0.007	0.1	0.32	1	-0.46	14	15
mol:PIP3	0.01	0.066	0.39	9	-0.84	1	10
AKT1	0.021	0.084	0.3	7	-0.74	1	8
PTK2B	0.028	0.015	-10000	0	-10000	0	0
RAPGEF1	0.004	0.096	0.3	1	-0.45	13	14
RANBP10	0.029	0.014	-10000	0	-10000	0	0
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
HGF/MET/SHIP2	0.054	0.059	-10000	0	-0.26	15	15
MAP3K5	0.001	0.11	0.26	1	-0.43	15	16
HGF/MET/CIN85/CBL/ENDOPHILINS	0.064	0.073	-10000	0	-0.25	20	20
AP1	-0.024	0.13	-10000	0	-0.3	89	89
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.027	0.025	-10000	0	-0.42	1	1
apoptosis	-0.14	0.34	-10000	0	-0.77	111	111
STAT3 (dimer)	0.01	0.069	-10000	0	-0.31	6	6
GAB1/CRKL/SHP2/PI3K	0.042	0.12	0.32	1	-0.42	14	15
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.024	0.095	-10000	0	-0.43	13	13
PTPN11	0.036	0.004	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.033	0.009	-10000	0	-10000	0	0
PTEN	0.027	0.061	-10000	0	-0.42	9	9
ELK1	-0.002	0.071	0.24	27	-10000	0	27
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.013	0.046	-10000	0	-0.21	5	5
PAK1	0.027	0.1	0.37	12	-0.71	1	13
HGF/MET/RANBP10	0.049	0.057	-10000	0	-0.25	13	13
HRAS	0.012	0.1	-10000	0	-0.47	16	16
DOCK1	0.003	0.097	0.3	2	-0.44	13	15
GAB1	0.008	0.1	-10000	0	-0.48	14	14
CRK	0.005	0.095	-10000	0	-0.44	14	14
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.017	0.1	-10000	0	-0.46	16	16
JUN	-0.001	0.12	-10000	0	-0.42	39	39
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.006	0.045	-10000	0	-0.21	18	18
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
cell morphogenesis	0.007	0.1	0.34	4	-0.37	6	10
GRB2/SHC	0.032	0.054	-10000	0	-0.21	9	9
FOS	-0.031	0.15	-10000	0	-0.42	66	66
GLMN	0.004	0.001	-10000	0	-10000	0	0
cell motility	-0.002	0.071	0.24	27	-10000	0	27
HGF/MET/MUC20	0.038	0.048	-10000	0	-0.25	13	13
cell migration	0.031	0.053	-10000	0	-0.21	9	9
GRB2	0.033	0.01	-10000	0	-10000	0	0
CBL	0.031	0.012	-10000	0	-10000	0	0
MET/RANBP10	0.038	0.04	-10000	0	-0.3	5	5
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.006	0.061	-10000	0	-0.23	16	16
MET/MUC20	0.021	0.033	-10000	0	-0.3	5	5
RAP1B	0.008	0.097	0.28	5	-0.42	12	17
RAP1A	0	0.096	0.28	1	-0.43	15	16
HGF/MET/RANBP9	0.058	0.055	-10000	0	-0.26	13	13
RAF1	0.016	0.1	-10000	0	-0.46	15	15
STAT3	0.009	0.068	-10000	0	-0.31	6	6
cell proliferation	0.042	0.1	0.28	21	-0.32	9	30
RPS6KB1	0.007	0.05	-10000	0	-0.28	11	11
MAPK3	-0.018	0.082	0.58	7	-10000	0	7
MAPK1	0.007	0.15	0.65	26	-10000	0	26
RANBP9	0.035	0.007	-10000	0	-10000	0	0
MAPK8	0.011	0.1	-10000	0	-0.4	15	15
SRC	0.008	0.062	-10000	0	-0.26	5	5
PI3K	0.031	0.077	-10000	0	-0.23	26	26
MET/Glomulin	0.019	0.041	-10000	0	-0.25	6	6
SOS1	0.034	0.021	-10000	0	-0.42	1	1
MAP2K1	0.014	0.098	-10000	0	-0.43	15	15
MET	0.029	0.046	-10000	0	-0.42	5	5
MAP4K1	0.008	0.1	0.28	1	-0.46	14	15
PTK2	0.027	0.015	-10000	0	-10000	0	0
MAP2K2	0.013	0.099	-10000	0	-0.42	16	16
BAD	0.016	0.081	0.33	4	-0.71	1	5
MAP2K4	-0.001	0.099	0.25	1	-0.4	15	16
SHP2/GRB2/SOS1/GAB1	0.044	0.095	-10000	0	-0.4	13	13
INPPL1	0.03	0.036	-10000	0	-0.42	3	3
PXN	0.036	0.004	-10000	0	-10000	0	0
SH3KBP1	0.027	0.061	-10000	0	-0.42	9	9
HGS	-0.001	0.041	-10000	0	-0.19	20	20
PLCgamma1/PKC	0.025	0.007	-10000	0	-10000	0	0
HGF	0.028	0.057	-10000	0	-0.42	8	8
RASA1	0.028	0.054	-10000	0	-0.42	7	7
NCK1	0.034	0.022	-10000	0	-0.42	1	1
PTPRJ	0.03	0.046	-10000	0	-0.42	5	5
NCK/PLCgamma1	0.046	0.055	-10000	0	-0.19	20	20
PDPK1	0.025	0.087	0.31	11	-0.78	1	12
HGF/MET/SHIP	0.038	0.048	-10000	0	-0.25	13	13

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.034	0.021	-10000	0	-0.42	1	1
HDAC3	0.035	0.005	-10000	0	-10000	0	0
VDR	0.02	0.083	-10000	0	-0.42	17	17
Cbp/p300/PCAF	0.04	0.023	-10000	0	-0.24	1	1
EP300	0.033	0.022	-10000	0	-0.42	1	1
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.014	0.056	0.19	1	-0.31	4	5
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.035	0.005	-10000	0	-10000	0	0
AKT1	0.027	0.093	0.21	56	-0.23	18	74
RAR alpha/9cRA/Cyclin H	0.045	0.1	0.26	1	-0.35	7	8
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.019	0.064	-10000	0	-0.22	17	17
CDC2	0.01	0.094	-10000	0	-0.42	22	22
response to UV	-0.002	0.008	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.03	0.062	-10000	0	-0.29	8	8
NCOR2	0.036	0.004	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.015	0.058	-10000	0	-0.3	17	17
RXRs/RARs/NRIP1/9cRA	-0.004	0.19	-10000	0	-0.53	52	52
NCOA2	0.025	0.047	-10000	0	-0.42	5	5
NCOA3	0.03	0.036	-10000	0	-0.42	3	3
NCOA1	0.031	0.045	-10000	0	-0.42	5	5
VDR/VDR/DNA	0.02	0.082	-10000	0	-0.42	17	17
RARG	0.031	0.018	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.046	0.01	-10000	0	-10000	0	0
MAPK3	0.026	0.029	-10000	0	-0.42	1	1
MAPK1	0.033	0.022	-10000	0	-0.42	1	1
MAPK8	0.027	0.041	-10000	0	-0.42	3	3
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.027	0.13	-10000	0	-0.43	11	11
RARA	0.009	0.047	-10000	0	-0.23	12	12
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.015	0.054	-10000	0	-0.2	13	13
PRKCA	0.024	0.032	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.008	0.2	-10000	0	-0.57	52	52
RXRG	0.01	0.047	-10000	0	-0.3	7	7
RXRA	0.016	0.09	-10000	0	-0.34	7	7
RXRB	0.017	0.037	-10000	0	-0.28	2	2
VDR/Vit D3/DNA	0.015	0.058	-10000	0	-0.3	17	17
RBP1	-0.028	0.15	-10000	0	-0.42	67	67
CRBP1/9-cic-RA	-0.019	0.11	-10000	0	-0.3	67	67
RARB	0.011	0.09	-10000	0	-0.42	20	20
PRKCG	0.028	0.032	-10000	0	-10000	0	0
MNAT1	0.035	0.007	-10000	0	-10000	0	0
RAR alpha/RXRs	0.004	0.14	0.41	1	-0.42	17	18
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.029	0.11	0.27	1	-0.37	11	12
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.075	0.23	1	-0.31	7	8
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.008	0.2	-10000	0	-0.58	52	52
positive regulation of DNA binding	0.033	0.095	-10000	0	-0.33	7	7
NRIP1	-0.071	0.38	-10000	0	-1.2	51	51
RXRs/RARs	0.011	0.16	0.33	1	-0.42	46	47
RXRs/RXRs/DNA/9cRA	-0.008	0.11	-10000	0	-0.38	10	10
PRKACA	0.036	0.004	-10000	0	-10000	0	0
CDK7	0.034	0.008	-10000	0	-10000	0	0
TFIIH	0.067	0.025	-10000	0	-0.24	1	1
RAR alpha/9cRA	0.065	0.067	-10000	0	-0.22	4	4
CCNH	0.034	0.022	-10000	0	-0.42	1	1
CREBBP	0.032	0.011	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.064	0.028	-10000	0	-0.2	1	1

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.045	0.046	-10000	0	-0.3	8	8
FBXW11	0.034	0.021	-10000	0	-0.42	1	1
NF kappa B1 p50/c-Rel	0.026	0.039	-10000	0	-0.25	8	8
NF kappa B1 p50/RelA/I kappa B alpha	0.004	0.099	-10000	0	-0.34	18	18
NFKBIA	-0.014	0.1	-10000	0	-0.24	73	73
MAPK14	0.035	0.005	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.03	0.021	-10000	0	-0.26	1	1
ARRB2	0.017	0.006	-10000	0	-10000	0	0
REL	0.024	0.07	-10000	0	-0.42	12	12
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.026	0.037	-10000	0	-0.25	7	7
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.03	0.017	-10000	0	-10000	0	0
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
NF kappa B1 p50 dimer	0.023	0.021	0.26	3	-10000	0	3
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
NFKB1	0.013	0.007	-10000	0	-10000	0	0
RELA	0.035	0.006	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	-0.004	0.099	-10000	0	-0.3	26	26
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.004	0.1	-10000	0	-0.35	18	18
SRC	0.032	0.03	-10000	0	-0.42	2	2
PI3K	0.035	0.067	-10000	0	-0.3	18	18
NF kappa B1 p50/RelA	-0.003	0.098	-10000	0	-0.3	25	25
IKBKB	0.029	0.014	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.034	0.021	-10000	0	-0.42	1	1
SYK	0.005	0.11	-10000	0	-0.42	33	33
I kappa B alpha/PIK3R1	-0.008	0.12	-10000	0	-0.37	25	25
cell death	0.003	0.097	-10000	0	-0.33	18	18
NF kappa B1 p105/c-Rel	0.026	0.039	-10000	0	-0.25	8	8
LCK	-0.018	0.14	-10000	0	-0.42	54	54
BCL3	0.028	0.057	-10000	0	-0.42	8	8

×

S1P4 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	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
GNAO1	0.03	0.014	-10000	0	-10000	0	0
CDC42/GTP	0.002	0.087	-10000	0	-0.26	22	22
PLCG1	-0.009	0.073	-10000	0	-0.28	19	19
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.027	0.057	-10000	0	-0.42	8	8
GNAI3	0.035	0.006	-10000	0	-10000	0	0
G12/G13	0.043	0.036	-10000	0	-0.3	4	4
cell migration	0.002	0.085	-10000	0	-0.26	22	22
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
MAPK3	-0.007	0.07	-10000	0	-0.28	18	18
MAPK1	-0.005	0.071	-10000	0	-0.28	19	19
S1P/S1P5/Gi	0	0.077	-10000	0	-0.24	40	40
GNAI1	0.017	0.085	-10000	0	-0.42	18	18
CDC42/GDP	0.025	0.006	-10000	0	-10000	0	0
S1P/S1P5/G12	0.024	0.004	-10000	0	-10000	0	0
RHOA	0.031	0.07	0.19	60	-0.24	12	72
S1P/S1P4/Gi	0	0.077	-10000	0	-0.24	40	40
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.024	0.067	-10000	0	-0.42	11	11
S1P/S1P4/G12/G13	0.037	0.029	-10000	0	-0.23	4	4
GNA12	0.035	0.006	-10000	0	-10000	0	0
GNA13	0.028	0.042	-10000	0	-0.42	4	4
CDC42	0.034	0.008	-10000	0	-10000	0	0

×

S1P5 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	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	0.002	0.09	0.26	28	-10000	0	28
GNAI2	0.027	0.057	-10000	0	-0.42	8	8
S1P/S1P5/G12	0.024	0.004	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.03	0.014	-10000	0	-10000	0	0
RhoA/GTP	-0.001	0.092	-10000	0	-0.26	28	28
negative regulation of cAMP metabolic process	0	0.077	-10000	0	-0.24	40	40
GNAZ	0.024	0.067	-10000	0	-0.42	11	11
GNAI3	0.035	0.006	-10000	0	-10000	0	0
GNA12	0.035	0.006	-10000	0	-10000	0	0
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0	0.077	-10000	0	-0.24	40	40
RhoA/GDP	0.02	0.043	-10000	0	-0.3	9	9
RHOA	0.026	0.061	-10000	0	-0.42	9	9
GNAI1	0.017	0.085	-10000	0	-0.42	18	18

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.008	0.002	-10000	0	-10000	0	0
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.046	0.027	-10000	0	-0.3	2	2
STXBP1	0.035	0.005	-10000	0	-10000	0	0
ACh/CHRNA1	0.015	0.046	-10000	0	-0.14	23	23
RAB3GAP2/RIMS1/UNC13B	0.051	0.039	-10000	0	-0.26	3	3
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.031	0.012	-10000	0	-10000	0	0
mol:ACh	-0.005	0.03	0.087	4	-0.11	18	22
RAB3GAP2	0.028	0.025	-10000	0	-0.42	1	1
STX1A/SNAP25/VAMP2	0.033	0.057	-10000	0	-0.18	3	3
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.015	0.046	-10000	0	-0.14	23	23
UNC13B	0.032	0.03	-10000	0	-0.42	2	2
CHRNA1	0.029	0.054	-10000	0	-0.42	7	7
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.044	0.11	-10000	0	-0.27	98	98
SNAP25	-0.001	0.043	-10000	0	-0.26	14	14
VAMP2	0.005	0.011	-10000	0	-0.23	1	1
SYT1	-0.064	0.18	-10000	0	-0.42	98	98
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.032	0.007	-10000	0	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.033	0.057	-10000	0	-0.18	3	3

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.028	0.057	-9999	-0.42	8	8
mol:S1P	0.001	0.002	-9999	-0.026	2	2
S1P1/S1P/Gi	-0.017	0.11	-9999	-0.3	43	43
GNAO1	0.03	0.015	-9999	-10000	0	0
S1P/S1P3/G12/G13	0.039	0.03	-9999	-0.23	4	4
AKT1	0.004	0.12	-9999	-0.47	27	27
AKT3	-0.001	0.11	-9999	-0.78	5	5
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.028	0.057	-9999	-0.42	8	8
GNAI2	0.028	0.058	-9999	-0.42	8	8
GNAI3	0.036	0.008	-9999	-10000	0	0
GNAI1	0.018	0.085	-9999	-0.42	18	18
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.001	0.002	-9999	-0.03	2	2
S1PR2	0	0	-9999	-10000	0	0
EDG1	0.011	0.099	-9999	-0.42	25	25
mol:Ca2+	0.006	0.08	-9999	-0.3	20	20
MAPK3	-0.002	0.073	-9999	-0.33	12	12
MAPK1	0	0.074	-9999	-0.32	14	14
JAK2	-0.013	0.1	-9999	-0.34	26	26
CXCR4	-0.016	0.1	-9999	-0.35	26	26
FLT1	0.028	0.055	-9999	-0.42	7	7
RhoA/GDP	0.02	0.043	-9999	-0.3	9	9
Rac1/GDP	0.026	0.004	-9999	-10000	0	0
SRC	-0.004	0.079	-9999	-0.34	15	15
S1P/S1P3/Gi	0.006	0.081	-9999	-0.31	20	20
RAC1	0.035	0.006	-9999	-10000	0	0
RhoA/GTP	0.005	0.094	-9999	-0.3	19	19
VEGFA	0.002	0.003	-9999	-0.04	2	2
S1P/S1P2/Gi	0.004	0.079	-9999	-0.29	22	22
VEGFR1 homodimer/VEGFA homodimer	0.025	0.04	-9999	-0.27	8	8
RHOA	0.026	0.061	-9999	-0.42	9	9
S1P/S1P3/Gq	-0.007	0.08	-9999	-0.23	51	51
GNAQ	0	0	-9999	-10000	0	0
GNAZ	0.024	0.067	-9999	-0.42	11	11
G12/G13	0.043	0.036	-9999	-0.3	4	4
GNA14	-0.01	0.13	-9999	-0.42	44	44
GNA15	0.029	0.046	-9999	-0.42	5	5
GNA12	0.035	0.006	-9999	-10000	0	0
GNA13	0.028	0.042	-9999	-0.42	4	4
GNA11	0.032	0.036	-9999	-0.42	3	3
Rac1/GTP	0.008	0.09	-9999	-0.31	16	16

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.025	0.16	-10000	0	-0.81	12	12
NCK1/PAK1/Dok-R	-0.027	0.074	-10000	0	-0.4	12	12
NCK1/Dok-R	0.033	0.14	-10000	0	-0.89	8	8
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
mol:beta2-estradiol	-0.007	0.015	0.31	1	-10000	0	1
RELA	0.035	0.006	-10000	0	-10000	0	0
SHC1	0.028	0.025	-10000	0	-0.42	1	1
Rac/GDP	0.026	0.004	-10000	0	-10000	0	0
F2	0.011	0.025	-10000	0	-10000	0	0
TNIP2	0.032	0.03	-10000	0	-0.42	2	2
NF kappa B/RelA	0.064	0.14	-10000	0	-0.79	9	9
FN1	-0.009	0.13	-10000	0	-0.42	48	48
PLD2	0.02	0.13	-10000	0	-0.85	9	9
PTPN11	0.036	0.004	-10000	0	-10000	0	0
GRB14	-0.063	0.18	-10000	0	-0.42	98	98
ELK1	0.024	0.13	-10000	0	-0.78	10	10
GRB7	0.024	0.058	-10000	0	-0.42	8	8
PAK1	0.014	0.085	-10000	0	-0.42	18	18
Tie2/Ang1/alpha5/beta1 Integrin	0.042	0.16	-10000	0	-0.88	9	9
CDKN1A	0.002	0.19	-10000	0	-0.74	24	24
ITGA5	0.033	0.035	-10000	0	-0.42	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.029	0.15	-10000	0	-0.86	9	9
CRK	0.031	0.023	-10000	0	-0.42	1	1
mol:NO	0.028	0.13	-10000	0	-0.58	12	12
PLG	0.02	0.13	-10000	0	-0.85	9	9
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.018	0.15	-10000	0	-0.81	10	10
GRB2	0.033	0.01	-10000	0	-10000	0	0
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
ANGPT2	-0.055	0.21	-10000	0	-0.77	21	21
BMX	0.009	0.15	-10000	0	-0.94	10	10
ANGPT1	0.015	0.034	-10000	0	-10000	0	0
tube development	-0.001	0.16	-10000	0	-0.67	17	17
ANGPT4	0.033	0.03	-10000	0	-0.42	2	2
response to hypoxia	0	0.01	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.008	0.16	-10000	0	-0.88	9	9
alpha5/beta1 Integrin	0.047	0.037	-10000	0	-0.3	5	5
FGF2	-0.002	0.11	-10000	0	-0.42	34	34
STAT5A (dimer)	0	0.2	-10000	0	-0.77	22	22
mol:L-citrulline	0.028	0.13	-10000	0	-0.58	12	12
AGTR1	-0.044	0.16	-10000	0	-0.42	78	78
MAPK14	0.021	0.18	-10000	0	-1.1	11	11
Tie2/SHP2	0.013	0.17	-10000	0	-0.88	11	11
TEK	0.007	0.17	-10000	0	-0.96	11	11
RPS6KB1	0.038	0.16	-10000	0	-0.81	11	11
Angiotensin II/AT1	-0.029	0.12	-10000	0	-0.3	78	78
Tie2/Ang1/GRB2	0.035	0.14	-10000	0	-0.85	9	9
MAPK3	0.026	0.13	-10000	0	-0.78	9	9
MAPK1	0.016	0.12	-10000	0	-0.8	9	9
Tie2/Ang1/GRB7	0.03	0.14	-10000	0	-0.86	9	9
NFKB1	0.035	0.005	-10000	0	-10000	0	0
MAPK8	0.021	0.13	-10000	0	-0.85	9	9
PI3K	0.022	0.18	-10000	0	-0.94	12	12
FES	0.016	0.19	-10000	0	-1	13	13
Crk/Dok-R	0.031	0.15	-10000	0	-0.86	9	9
Tie2/Ang1/ABIN2	0.036	0.14	-10000	0	-0.86	9	9
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.028	0.15	-10000	0	-0.71	13	13
STAT5A	0.028	0.037	-10000	0	-0.42	3	3
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.057	0.17	-10000	0	-0.79	10	10
Tie2/Ang2	-0.009	0.21	-10000	0	-1	13	13
Tie2/Ang1	0.027	0.14	-10000	0	-0.9	9	9
FOXO1	0.028	0.15	-10000	0	-0.72	13	13
ELF1	0.034	0.054	-10000	0	-0.32	9	9
ELF2	0.027	0.13	-10000	0	-0.85	9	9
mol:Choline	0.02	0.12	-10000	0	-0.82	9	9
cell migration	-0.013	0.051	-10000	0	-0.22	15	15
FYN	-0.005	0.18	-10000	0	-0.81	15	15
DOK2	0.01	0.085	-10000	0	-0.42	18	18
negative regulation of cell cycle	0.006	0.17	-10000	0	-0.66	24	24
ETS1	0.035	0.028	-10000	0	-0.43	1	1
PXN	0.057	0.15	0.39	1	-0.64	11	12
ITGB1	0.033	0.03	-10000	0	-0.42	2	2
NOS3	0.026	0.14	-10000	0	-0.66	12	12
RAC1	0.035	0.006	-10000	0	-10000	0	0
TNF	0.033	0.065	-10000	0	-0.42	10	10
MAPKKK cascade	0.02	0.12	-10000	0	-0.82	9	9
RASA1	0.028	0.054	-10000	0	-0.42	7	7
Tie2/Ang1/Shc	0.029	0.14	-10000	0	-0.9	8	8
NCK1	0.034	0.022	-10000	0	-0.42	1	1
vasculogenesis	0.029	0.12	-10000	0	-0.52	12	12
mol:Phosphatidic acid	0.02	0.12	-10000	0	-0.82	9	9
mol:Angiotensin II	0.001	0.002	-10000	0	-10000	0	0
mol:NADP	0.028	0.13	-10000	0	-0.58	12	12
Rac1/GTP	0.036	0.15	-10000	0	-0.74	12	12
MMP2	0.013	0.14	-10000	0	-0.97	8	8

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	-0.039	0.048	0.31	6	-10000	0	6
KIRREL	0.025	0.053	-10000	0	-0.43	6	6
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.039	0.048	-10000	0	-0.31	6	6
PLCG1	0.033	0.009	-10000	0	-10000	0	0
ARRB2	0.032	0.011	-10000	0	-10000	0	0
WASL	0.029	0.054	-10000	0	-0.42	7	7
Nephrin/NEPH1/podocin/CD2AP	0.064	0.057	-10000	0	-0.24	6	6
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.021	0.044	-10000	0	-0.21	12	12
FYN	0.059	0.1	0.28	70	-0.21	11	81
mol:Ca2+	0.057	0.056	-10000	0	-0.24	6	6
mol:DAG	0.058	0.057	-10000	0	-0.24	6	6
NPHS2	0.03	0.029	-10000	0	-0.43	1	1
mol:IP3	0.058	0.057	-10000	0	-0.24	6	6
regulation of endocytosis	0.046	0.055	-10000	0	-0.2	11	11
Nephrin/NEPH1/podocin/Cholesterol	0.048	0.049	-10000	0	-0.24	6	6
establishment of cell polarity	0.039	0.048	-10000	0	-0.31	6	6
Nephrin/NEPH1/podocin/NCK1-2	0.075	0.064	-10000	0	-0.22	7	7
Nephrin/NEPH1/beta Arrestin2	0.051	0.058	-10000	0	-0.2	11	11
NPHS1	0.041	0.03	-10000	0	-0.39	1	1
Nephrin/NEPH1/podocin	0.048	0.055	0.2	12	-0.21	11	23
TJP1	0.031	0.036	-10000	0	-0.42	3	3
NCK1	0.034	0.022	-10000	0	-0.42	1	1
NCK2	0.036	0.004	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.06	0.058	-10000	0	-0.24	6	6
CD2AP	0.035	0.007	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.06	0.057	-10000	0	-0.24	6	6
GRB2	0.033	0.01	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	0.058	0.11	0.29	70	-0.23	11	81
cytoskeleton organization	0.023	0.068	0.24	31	-0.25	6	37
Nephrin/NEPH1	0.033	0.036	-10000	0	-0.21	6	6
Nephrin/NEPH1/ZO-1	0.05	0.054	-10000	0	-0.25	9	9

×

BARD1 signaling events

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
BARD1/CSTF1	0.044	0.036	-10000	0	-0.3	4	4
ATM	0.031	0.013	-10000	0	-10000	0	0
UBE2D3	0.035	0.005	-10000	0	-10000	0	0
PRKDC	0.029	0.031	-10000	0	-0.42	2	2
ATR	0.035	0.006	-10000	0	-10000	0	0
UBE2L3	0.034	0.009	-10000	0	-10000	0	0
FANCD2	0.023	0.011	-10000	0	-10000	0	0
protein ubiquitination	0.059	0.072	-10000	0	-0.23	20	20
XRCC5	0.036	0.004	-10000	0	-10000	0	0
XRCC6	0.033	0.009	-10000	0	-10000	0	0
M/R/N Complex	0.047	0.044	-10000	0	-0.26	4	4
MRE11A	0.031	0.012	-10000	0	-10000	0	0
DNA-PK	0.056	0.036	-10000	0	-0.25	2	2
FA complex/FANCD2/Ubiquitin	0.001	0.097	-10000	0	-0.42	12	12
FANCF	0.031	0.041	-10000	0	-0.42	4	4
BRCA1	0.021	0.07	-10000	0	-0.42	12	12
CCNE1	0.027	0.046	-10000	0	-0.42	5	5
CDK2/Cyclin E1	0.044	0.045	-10000	0	-0.34	6	6
FANCG	0.035	0.006	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.037	0.062	-10000	0	-0.3	15	15
FANCE	0.032	0.036	-10000	0	-0.42	3	3
FANCC	0.034	0.021	-10000	0	-0.42	1	1
NBN	0.027	0.025	-10000	0	-0.42	1	1
FANCA	0.015	0.067	-10000	0	-0.42	11	11
DNA repair	-0.016	0.12	0.28	3	-0.35	16	19
BRCA1/BARD1/ubiquitin	0.037	0.062	-10000	0	-0.3	15	15
BARD1/DNA-PK	0.069	0.049	-10000	0	-0.23	5	5
FANCL	0.035	0.006	-10000	0	-10000	0	0
mRNA polyadenylation	-0.044	0.035	0.3	4	-10000	0	4
BRCA1/BARD1/CTIP/M/R/N Complex	0.017	0.08	-10000	0	-0.22	38	38
BRCA1/BACH1/BARD1/TopBP1	0.054	0.06	-10000	0	-0.26	15	15
BRCA1/BARD1/P53	0.049	0.091	-10000	0	-0.25	35	35
BARD1/CSTF1/BRCA1	0.049	0.06	-10000	0	-0.26	14	14
BRCA1/BACH1	0.021	0.07	-10000	0	-0.42	12	12
BARD1	0.033	0.035	-10000	0	-0.42	3	3
PCNA	0.03	0.041	-10000	0	-0.42	4	4
BRCA1/BARD1/UbcH5C	0.054	0.06	-10000	0	-0.26	15	15
BRCA1/BARD1/UbcH7	0.052	0.059	-10000	0	-0.26	14	14
BRCA1/BARD1/RAD51/PCNA	0.037	0.11	-10000	0	-0.24	58	58
BARD1/DNA-PK/P53	0.057	0.085	-10000	0	-0.22	29	29
BRCA1/BARD1/Ubiquitin	0.037	0.062	-10000	0	-0.3	15	15
BRCA1/BARD1/CTIP	0.033	0.063	-10000	0	-0.23	22	22
FA complex	0.019	0.057	-10000	0	-0.4	2	2
BARD1/EWS	0.047	0.031	-10000	0	-0.3	3	3
RBBP8	0.007	0.044	-10000	0	-0.3	10	10
TP53	0.008	0.1	-10000	0	-0.42	26	26
TOPBP1	0.035	0.006	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.047	0.09	0.25	35	-10000	0	35
BRCA1/BARD1	0.066	0.076	-10000	0	-0.23	20	20
CSTF1	0.031	0.023	-10000	0	-0.42	1	1
BARD1/EWS-Fli1	0.024	0.025	-10000	0	-0.3	3	3
CDK2	0.033	0.029	-10000	0	-0.42	2	2
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.005	0.13	-10000	0	-0.42	43	43
RAD50	0.03	0.046	-10000	0	-0.42	5	5
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.037	0.062	-10000	0	-0.3	15	15
EWSR1	0.034	0.009	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.012	0.06	-10000	0	-0.34	13	13
CRKL	0.03	0.041	-10000	0	-0.42	4	4
Rac1/GDP	0.026	0.004	-10000	0	-10000	0	0
DOCK1	0.027	0.057	-10000	0	-0.42	8	8
ITGA4	0.021	0.078	-10000	0	-0.42	15	15
alpha4/beta7 Integrin/MAdCAM1	0.068	0.075	-10000	0	-0.25	22	22
EPO	0.03	0.014	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.041	0.061	-10000	0	-0.3	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.031	0.023	-10000	0	-0.42	1	1
alpha4/beta1 Integrin	0.039	0.068	-10000	0	-0.34	15	15
EPO/EPOR (dimer)	0.047	0.014	-10000	0	-10000	0	0
lamellipodium assembly	0.012	0.084	-10000	0	-0.49	5	5
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
PI3K	0.035	0.067	-10000	0	-0.3	18	18
ARF6	0.033	0.029	-10000	0	-0.42	2	2
JAK2	0.024	0.048	-10000	0	-0.26	13	13
PXN	0.036	0.004	-10000	0	-10000	0	0
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
MADCAM1	0.034	0.008	-10000	0	-10000	0	0
cell adhesion	0.065	0.074	-10000	0	-0.25	22	22
CRKL/CBL	0.042	0.036	-10000	0	-0.3	4	4
ITGB1	0.033	0.03	-10000	0	-0.42	2	2
SRC	0.001	0.084	0.19	15	-0.27	37	52
ITGB7	0.036	0.004	-10000	0	-10000	0	0
RAC1	0.035	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.04	0.099	-10000	0	-0.3	36	36
p130Cas/Crk/Dock1	0.02	0.087	-10000	0	-0.25	25	25
VCAM1	0.009	0.1	-10000	0	-0.42	27	27
RHOA	0.026	0.061	-10000	0	-0.42	9	9
alpha4/beta1 Integrin/Paxillin/GIT1	0.073	0.067	-10000	0	-0.26	16	16
BCAR1	-0.024	0.072	0.18	15	-0.25	34	49
EPOR	0.035	0.005	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.031	0.012	-10000	0	-10000	0	0
GIT1	0.033	0.022	-10000	0	-0.42	1	1
Rac1/GTP	0.012	0.086	-10000	0	-0.51	5	5

×

Signaling events mediated by HDAC Class III

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.033	0.022	-10000	0	-0.42	1	1
HDAC4	0.034	0.021	-10000	0	-0.42	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.005	0.016	-10000	0	-0.11	8	8
CDKN1A	-0.018	0.095	0.4	1	-0.57	13	14
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.035	0.007	-10000	0	-10000	0	0
FOXO3	-0.007	0.016	0.34	1	-10000	0	1
FOXO1	0	0	-10000	0	-10000	0	0
FOXO4	0.011	0.02	-10000	0	-0.42	1	1
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.033	0.009	-10000	0	-10000	0	0
TAT	0.027	0.016	-10000	0	-10000	0	0
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.006	0.065	-10000	0	-0.3	24	24
PPARGC1A	0.023	0.064	-10000	0	-0.42	10	10
FHL2	-0.026	0.15	-10000	0	-0.42	65	65
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.048	0.019	-10000	0	-10000	0	0
HIST2H4A	-0.005	0.016	0.11	8	-10000	0	8
SIRT1/FOXO3a	0.028	0.038	0.2	7	-0.2	3	10
SIRT1	0.035	0.019	0.21	4	-10000	0	4
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.053	0.036	-10000	0	-0.26	1	1
SIRT1/Histone H1b	0.021	0.077	-10000	0	-0.22	31	31
apoptosis	-0.063	0.024	-10000	0	-10000	0	0
SIRT1/PGC1A	0.038	0.044	-10000	0	-0.25	10	10
p53/SIRT1	0.025	0.079	0.4	4	-0.31	22	26
SIRT1/FOXO4	0.032	0.044	-10000	0	-0.18	5	5
FOXO1/FHL2/SIRT1	0.008	0.09	0.15	4	-0.23	63	67
HIST1H1E	0	0.065	-10000	0	-0.26	30	30
SIRT1/p300	0.048	0.022	0.18	3	-0.23	1	4
muscle cell differentiation	-0.008	0.061	0.26	24	-0.15	5	29
TP53	0.009	0.095	0.21	4	-0.43	22	26
KU70/SIRT1/BAX	0.064	0.024	-10000	0	-10000	0	0
CREBBP	0.032	0.011	-10000	0	-10000	0	0
MEF2D	0.028	0.015	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.04	0.024	-10000	0	-10000	0	0
ACSS2	-0.006	0.025	0.19	4	-10000	0	4
SIRT1/PCAF/MYOD	0.008	0.061	0.16	6	-0.26	24	30

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.035	0.006	-10000	0	-10000	0	0
NFATC1	0.019	0.092	0.3	2	-0.38	9	11
NFATC2	0.018	0.049	0.16	1	-0.2	6	7
NFATC3	0.013	0.007	-10000	0	-10000	0	0
YWHAE	0.032	0.011	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.019	0.091	0.21	4	-0.36	11	15
Exportin 1/Ran/NUP214	0.069	0.022	-10000	0	-0.26	1	1
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.042	0.086	-10000	0	-0.44	4	4
BCL2/BAX	-0.018	0.14	-10000	0	-0.3	95	95
CaM/Ca2+/Calcineurin A alpha-beta B1	0.027	0.006	-10000	0	-10000	0	0
CaM/Ca2+	0.027	0.006	-10000	0	-10000	0	0
BAX	0.035	0.007	-10000	0	-10000	0	0
MAPK14	0.036	0.005	-10000	0	-10000	0	0
BAD	0.034	0.021	-10000	0	-0.42	1	1
CABIN1/MEF2D	0.029	0.083	-10000	0	-0.37	7	7
Calcineurin A alpha-beta B1/BCL2	-0.057	0.18	-10000	0	-0.42	99	99
FKBP8	0.035	0.005	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.029	0.082	0.37	7	-10000	0	7
KPNB1	0.031	0.041	-10000	0	-0.42	4	4
KPNA2	0.023	0.061	-10000	0	-0.42	9	9
XPO1	0.035	0.005	-10000	0	-10000	0	0
SFN	0.011	0.099	-10000	0	-0.42	25	25
MAP3K8	0.003	0.11	-10000	0	-0.42	32	32
NFAT4/CK1 alpha	0.016	0.057	-10000	0	-0.21	23	23
MEF2D/NFAT1/Cbp/p300	0.055	0.064	-10000	0	-0.23	2	2
CABIN1	0.019	0.09	0.21	4	-0.37	10	14
CALM1	0.035	0.007	-10000	0	-10000	0	0
RAN	0.035	0.005	-10000	0	-10000	0	0
MAP3K1	0.01	0.099	-10000	0	-0.42	25	25
CAMK4	0.032	0.03	-10000	0	-0.42	2	2
mol:Ca2+	0.001	0.001	-10000	0	-10000	0	0
MAPK3	0.032	0.023	-10000	0	-0.42	1	1
YWHAH	0.031	0.036	-10000	0	-0.42	3	3
Calcineurin A alpha-beta B1/AKAP79/PKA	0.023	0.092	-10000	0	-0.3	37	37
YWHAB	0.034	0.009	-10000	0	-10000	0	0
MAPK8	0.033	0.035	-10000	0	-0.42	3	3
MAPK9	0.018	0.087	-10000	0	-0.42	19	19
YWHAG	0.035	0.005	-10000	0	-10000	0	0
FKBP1A	0.034	0.008	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.031	0.093	0.32	1	-0.36	8	9
PRKCH	0.03	0.046	-10000	0	-0.42	5	5
CABIN1/Cbp/p300	0.045	0.025	-10000	0	-0.28	1	1
CASP3	0.035	0.008	-10000	0	-10000	0	0
PIM1	0.035	0.007	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.024	0.005	-10000	0	-10000	0	0
apoptosis	0.002	0.048	-10000	0	-0.29	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.028	0.059	-10000	0	-0.23	3	3
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.031	0.046	-10000	0	-0.42	5	5
JNK2/NFAT4	-0.002	0.08	-10000	0	-0.21	25	25
BAD/BCL-XL	0.049	0.02	-10000	0	-0.3	1	1
PRKCD	0.032	0.03	-10000	0	-0.42	2	2
NUP214	0.035	0.021	-10000	0	-0.42	1	1
PRKCZ	0	0	-10000	0	-10000	0	0
PRKCA	0.031	0.012	-10000	0	-10000	0	0
PRKCG	0.036	0	-10000	0	-10000	0	0
PRKCQ	0.025	0.054	-10000	0	-0.42	7	7
FKBP38/BCL2	-0.019	0.14	-10000	0	-0.3	97	97
EP300	0.033	0.022	-10000	0	-0.42	1	1
PRKCB1	0.003	0.11	-10000	0	-0.42	29	29
CSNK2A1	0.034	0.008	-10000	0	-10000	0	0
NFATc/JNK1	0.036	0.096	0.31	2	-0.36	9	11
CaM/Ca2+/FKBP38	0.047	0.011	-10000	0	-10000	0	0
FKBP12/FK506	0.025	0.006	-10000	0	-10000	0	0
CSNK1A1	0.018	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.045	0.023	-10000	0	-0.25	2	2
NFATc/ERK1	0.033	0.092	0.31	2	-0.35	8	10
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.05	0.096	-10000	0	-0.38	7	7
NR4A1	0.064	0.079	0.23	15	-0.43	1	16
GSK3B	0.036	0.005	-10000	0	-10000	0	0
positive T cell selection	0.013	0.007	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.021	0.036	-10000	0	-0.21	1	1
RCH1/ KPNB1	0.037	0.056	-10000	0	-0.3	12	12
YWHAQ	0.033	0.029	-10000	0	-0.42	2	2
PRKACA	0.036	0.005	-10000	0	-10000	0	0
AKAP5	-0.001	0.12	-10000	0	-0.42	38	38
MEF2D	0.028	0.015	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.026	0.016	-10000	0	-10000	0	0
NFATc/p38 alpha	0.037	0.094	0.33	1	-0.36	9	10
CREBBP	0.033	0.011	-10000	0	-10000	0	0
BCL2	-0.057	0.18	-10000	0	-0.42	99	99

×

Paxillin-dependent events mediated by a4b1

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.03	0.041	-10000	0	-0.42	4	4
Rac1/GDP	0.035	0.013	-10000	0	-10000	0	0
DOCK1	0.027	0.057	-10000	0	-0.42	8	8
ITGA4	0.021	0.078	-10000	0	-0.42	15	15
RAC1	0.035	0.006	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.041	0.061	-10000	0	-0.3	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.031	0.023	-10000	0	-0.42	1	1
alpha4/beta1 Integrin	0.058	0.064	-10000	0	-0.29	15	15
alpha4/beta7 Integrin/Paxillin	0.048	0.051	-10000	0	-0.24	15	15
lamellipodium assembly	-0.014	0.13	-10000	0	-0.43	32	32
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
PI3K	0.035	0.067	-10000	0	-0.3	18	18
ARF6	0.033	0.029	-10000	0	-0.42	2	2
TLN1	0.034	0.021	-10000	0	-0.42	1	1
PXN	0.016	0.003	-10000	0	-10000	0	0
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
ARF6/GTP	0.059	0.062	-10000	0	-0.23	18	18
cell adhesion	0.061	0.062	-10000	0	-0.25	16	16
CRKL/CBL	0.042	0.036	-10000	0	-0.3	4	4
alpha4/beta1 Integrin/Paxillin	0.046	0.057	-10000	0	-0.26	15	15
ITGB1	0.033	0.03	-10000	0	-0.42	2	2
ITGB7	0.036	0.004	-10000	0	-10000	0	0
ARF6/GDP	0.033	0.031	-10000	0	-0.42	2	2
alpha4/beta1 Integrin/Paxillin/VCAM1	0.049	0.092	-10000	0	-0.26	36	36
p130Cas/Crk/Dock1	0.049	0.052	-10000	0	-0.25	9	9
VCAM1	0.009	0.1	-10000	0	-0.42	27	27
alpha4/beta1 Integrin/Paxillin/Talin	0.064	0.063	-10000	0	-0.25	16	16
alpha4/beta1 Integrin/Paxillin/GIT1	0.063	0.063	-10000	0	-0.25	16	16
BCAR1	0.029	0.014	-10000	0	-10000	0	0
mol:GDP	-0.061	0.062	0.24	16	-10000	0	16
CBL	0.031	0.012	-10000	0	-10000	0	0
PRKACA	0.036	0.004	-10000	0	-10000	0	0
GIT1	0.033	0.022	-10000	0	-0.42	1	1
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.064	0.063	-10000	0	-0.25	16	16
Rac1/GTP	-0.018	0.14	-10000	0	-0.48	32	32

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.009	0.11	-10000	0	-0.42	29	29
HRAS	0.032	0.036	-10000	0	-0.42	3	3
EGFR	-0.013	0.13	-10000	0	-0.42	47	47
AKT	0.025	0.085	0.26	3	-0.28	11	14
FOXO3	0	0	-10000	0	-10000	0	0
AKT1	0.032	0.036	-10000	0	-0.42	3	3
FOXO1	0	0	-10000	0	-10000	0	0
AKT3	0.024	0.032	-10000	0	-0.42	2	2
FOXO4	0	0	-10000	0	-10000	0	0
MET	0.029	0.046	-10000	0	-0.42	5	5
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
PIK3CB	0.03	0.046	-10000	0	-0.42	5	5
NRAS	0.029	0.05	-10000	0	-0.42	6	6
PIK3CG	0.022	0.073	-10000	0	-0.42	13	13
PIK3R3	0.025	0.067	-10000	0	-0.42	11	11
PIK3R2	0.036	0.004	-10000	0	-10000	0	0
NF1	0.032	0.03	-10000	0	-0.42	2	2
RAS	-0.003	0.077	0.17	3	-0.29	21	24
ERBB2	0.017	0.078	-10000	0	-0.42	15	15
proliferation/survival/translation	-0.026	0.057	0.24	8	-0.18	4	12
PI3K	0.003	0.085	0.2	7	-0.23	37	44
PIK3R1	0.018	0.083	-10000	0	-0.42	17	17
KRAS	0.027	0.057	-10000	0	-0.42	8	8
FOXO	0.042	0.039	0.19	7	-10000	0	7
AKT2	0.035	0.005	-10000	0	-10000	0	0
PTEN	0.027	0.061	-10000	0	-0.42	9	9

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.075	0.048	-10000	0	-0.23	6	6
HDAC3	0.035	0.005	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.013	0.009	-10000	0	-0.2	1	1
GATA1/HDAC4	0.051	0.019	-10000	0	-0.3	1	1
GATA1/HDAC5	0.049	0.021	-10000	0	-0.3	1	1
GATA2/HDAC5	0.044	0.041	-10000	0	-0.3	6	6
HDAC5/BCL6/BCoR	0.048	0.075	-10000	0	-0.26	26	26
HDAC9	0.033	0.022	-10000	0	-0.42	1	1
Glucocorticoid receptor/Hsp90/HDAC6	0.038	0.052	-10000	0	-0.25	15	15
HDAC4/ANKRA2	0.04	0.059	-10000	0	-0.3	14	14
HDAC5/YWHAB	0.046	0.024	-10000	0	-0.3	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.016	0.011	-10000	0	-0.17	1	1
GATA2	0.029	0.046	-10000	0	-0.42	5	5
HDAC4/RFXANK	0.05	0.02	-10000	0	-0.3	1	1
BCOR	0.028	0.061	-10000	0	-0.42	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.031	0.03	-10000	0	-0.42	2	2
HDAC5	0.033	0.022	-10000	0	-0.42	1	1
GNB1/GNG2	0.048	0.039	-10000	0	-0.3	6	6
Histones	0.008	0.068	-10000	0	-0.23	28	28
ADRBK1	0.033	0.01	-10000	0	-10000	0	0
HDAC4	0.034	0.021	-10000	0	-0.42	1	1
XPO1	0.035	0.005	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.038	0.06	-10000	0	-0.3	14	14
HDAC4/Ubc9	0.045	0.024	-10000	0	-0.3	1	1
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.046	0.024	-10000	0	-0.3	1	1
TUBA1B	0	0	-10000	0	-10000	0	0
HDAC6	0.036	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.048	0.022	-10000	0	-0.3	1	1
CAMK4	0.032	0.03	-10000	0	-0.42	2	2
Tubulin/HDAC6	0.036	0.055	-10000	0	-0.25	17	17
SUMO1	0.036	0.004	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.034	0.009	-10000	0	-10000	0	0
GATA1	0.036	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.032	0.011	-10000	0	-10000	0	0
NR3C1	0.022	0.078	-10000	0	-0.42	15	15
SUMO1/HDAC4	0.051	0.044	-10000	0	-0.21	2	2
SRF	0.035	0.007	-10000	0	-10000	0	0
HDAC4/YWHAB	0.048	0.022	-10000	0	-0.3	1	1
Tubulin	0.014	0.058	-10000	0	-0.3	17	17
HDAC4/14-3-3 E	0.046	0.023	-10000	0	-0.29	1	1
GNB1	0.032	0.045	-10000	0	-0.42	5	5
RANGAP1	0.032	0.022	-10000	0	-0.42	1	1
BCL6/BCoR	0.032	0.08	-10000	0	-0.3	27	27
HDAC4/HDAC3/SMRT (N-CoR2)	0.068	0.023	-10000	0	-0.26	1	1
HDAC4/SRF	0.064	0.033	-10000	0	-0.26	3	3
HDAC4/ER alpha	-0.045	0.15	-10000	0	-0.3	131	131
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.008	0.068	-10000	0	-0.22	28	28
cell motility	0.036	0.055	-10000	0	-0.25	17	17
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.032	0.011	-10000	0	-10000	0	0
HDAC7/HDAC3	0.026	0.004	-10000	0	-10000	0	0
BCL6	0.018	0.085	-10000	0	-0.42	18	18
HDAC4/CaMK II delta B	0.034	0.021	-10000	0	-0.42	1	1
Hsp90/HDAC6	0.027	0	-10000	0	-10000	0	0
ESR1	-0.088	0.2	-10000	0	-0.42	130	130
HDAC6/HDAC11	0.034	0.077	-10000	0	-0.3	25	25
Ran/GTP/Exportin 1	0.053	0.042	-10000	0	-0.24	1	1
NPC	0.021	0.002	-10000	0	-10000	0	0
MEF2C	0.016	0.089	-10000	0	-0.42	20	20
RAN	0.035	0.005	-10000	0	-10000	0	0
HDAC4/MEF2C	0.076	0.072	-10000	0	-0.22	19	19
GNG2	0.034	0.021	-10000	0	-0.42	1	1
NCOR2	0.036	0.004	-10000	0	-10000	0	0
TUBB2A	0.019	0.083	-10000	0	-0.42	17	17
HDAC11	0.012	0.099	-10000	0	-0.42	25	25
HSP90AA1	0	0	-10000	0	-10000	0	0
RANBP2	0.036	0.004	-10000	0	-10000	0	0
ANKRA2	0.022	0.073	-10000	0	-0.42	13	13
RFXANK	0.035	0.005	-10000	0	-10000	0	0
nuclear import	-0.036	0.028	0.26	2	-10000	0	2

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.033	0.03	-9999	-0.42	2	2
ITGB7	0.036	0.004	-9999	-10000	0	0
ITGA4	0.021	0.078	-9999	-0.42	15	15
alpha4/beta7 Integrin	0.041	0.061	-9999	-0.3	15	15
alpha4/beta1 Integrin	0.039	0.068	-9999	-0.34	15	15

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.016	0.003	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.041	0.031	-10000	0	-0.24	1	1
CDKN1B	0.01	0.082	0.22	8	-0.34	15	23
CDKN1A	0.011	0.073	0.2	4	-0.33	15	19
FRAP1	0.034	0.008	-10000	0	-10000	0	0
PRKDC	0.029	0.031	-10000	0	-0.42	2	2
FOXO3	0.011	0.061	-10000	0	-0.31	15	15
AKT1	0.011	0.064	-10000	0	-0.33	15	15
BAD	0.034	0.021	-10000	0	-0.42	1	1
AKT3	0.011	0.025	-10000	0	-0.29	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.011	0.061	-10000	0	-0.31	15	15
AKT1/ASK1	0.037	0.087	0.24	4	-0.3	16	20
BAD/YWHAZ	0.05	0.036	-10000	0	-0.26	1	1
RICTOR	0.035	0.007	-10000	0	-10000	0	0
RAF1	0.035	0.006	-10000	0	-10000	0	0
JNK cascade	-0.035	0.084	0.3	16	-0.22	3	19
TSC1	0.014	0.065	-10000	0	-0.32	14	14
YWHAZ	0.026	0.016	-10000	0	-10000	0	0
AKT1/RAF1	0.054	0.083	0.27	5	-0.32	15	20
EP300	0.033	0.022	-10000	0	-0.42	1	1
mol:GDP	0.011	0.064	-10000	0	-0.32	15	15
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.008	0.065	0.25	1	-0.33	15	16
YWHAQ	0.033	0.029	-10000	0	-0.42	2	2
TBC1D4	0.004	0.034	0.24	2	-0.24	8	10
MAP3K5	0.013	0.093	-10000	0	-0.42	22	22
MAPKAP1	0.035	0.021	-10000	0	-0.42	1	1
negative regulation of cell cycle	-0.035	0.075	0.23	9	-0.2	7	16
YWHAH	0.031	0.036	-10000	0	-0.42	3	3
AKT1S1	0.017	0.077	0.21	14	-0.32	16	30
CASP9	0.016	0.055	-10000	0	-0.29	11	11
YWHAB	0.034	0.009	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.044	0.099	0.27	10	-0.33	15	25
GBL	0.031	0.023	-10000	0	-0.42	1	1
PDK1/Src/Hsp90	0.041	0.025	-10000	0	-0.25	2	2
YWHAE	0.032	0.011	-10000	0	-10000	0	0
SRC	0.032	0.03	-10000	0	-0.42	2	2
AKT2/p21CIP1	0.014	0.068	0.21	5	-0.35	8	13
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.036	0.076	-10000	0	-0.37	12	12
CHUK	0.01	0.074	0.2	1	-0.33	15	16
BAD/BCL-XL	0.055	0.081	0.26	3	-0.3	15	18
mTORC2	0.075	0.04	-10000	0	-0.23	2	2
AKT2	0.016	0.015	-10000	0	-0.29	1	1
FOXO1-3a-4/14-3-3 family	0.046	0.095	0.24	18	-0.32	9	27
PDPK1	0.032	0.023	-10000	0	-0.42	1	1
MDM2	0.016	0.071	0.22	4	-0.32	15	19
MAPKKK cascade	-0.053	0.082	0.31	15	-0.26	6	21
MDM2/Cbp/p300	0.054	0.081	0.29	6	-0.3	15	21
TSC1/TSC2	0.016	0.084	0.3	19	-0.32	15	34
proteasomal ubiquitin-dependent protein catabolic process	0.051	0.078	0.28	6	-0.29	15	21
glucose import	-0.003	0.03	0.21	2	-0.22	8	10
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.032	0.084	0.26	1	-0.44	8	9
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.003	0.031	0.21	2	-0.22	8	10
GSK3A	0.014	0.067	0.2	2	-0.32	15	17
FOXO1	0.011	0.061	-10000	0	-0.31	15	15
GSK3B	0.014	0.067	-10000	0	-0.32	15	15
SFN	0.011	0.099	-10000	0	-0.42	25	25
G1/S transition of mitotic cell cycle	0.02	0.075	0.26	3	-0.31	15	18
p27Kip1/14-3-3 family	0.021	0.054	-10000	0	-0.34	2	2
PRKACA	0.036	0.004	-10000	0	-10000	0	0
KPNA1	0.035	0.005	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
YWHAG	0.035	0.005	-10000	0	-10000	0	0
RHEB	0.035	0.007	-10000	0	-10000	0	0
CREBBP	0.032	0.011	-10000	0	-10000	0	0

×

Signaling events mediated by PRL

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.027	0.046	-10000	0	-0.42	5	5
mol:Halofuginone	0.004	0.009	-10000	0	-0.19	1	1
ITGA1	0.023	0.073	-10000	0	-0.42	13	13
CDKN1A	-0.005	0.12	-10000	0	-0.44	28	28
PRL-3/alpha Tubulin	0.02	0.018	-10000	0	-0.3	1	1
mol:Ca2+	-0.037	0.083	0.34	1	-0.32	39	40
AGT	-0.024	0.14	-10000	0	-0.42	54	54
CCNA2	-0.037	0.096	-10000	0	-0.52	3	3
TUBA1B	0	0	-10000	0	-10000	0	0
EGR1	-0.028	0.11	-10000	0	-0.29	76	76
CDK2/Cyclin E1	0.021	0.12	-10000	0	-0.44	22	22
MAPK3	0.011	0.016	-10000	0	-0.3	1	1
PRL-2 /Rab GGTase beta	0.046	0.043	-10000	0	-0.3	7	7
MAPK1	0.011	0.016	-10000	0	-0.3	1	1
PTP4A1	-0.027	0.083	-10000	0	-0.48	3	3
PTP4A3	0.027	0.025	-10000	0	-0.42	1	1
PTP4A2	0.028	0.054	-10000	0	-0.42	7	7
ITGB1	0.011	0.021	-10000	0	-0.3	2	2
SRC	0.032	0.03	-10000	0	-0.42	2	2
RAC1	0.013	0.059	-10000	0	-0.63	2	2
Rab GGTase beta/Rab GGTase alpha	0.05	0.013	-10000	0	-10000	0	0
PRL-1/ATF-5	0.001	0.096	0.37	1	-0.46	3	4
RABGGTA	0.035	0.007	-10000	0	-10000	0	0
BCAR1	-0.017	0.021	0.34	1	-10000	0	1
RHOC	0.01	0.071	-10000	0	-0.51	5	5
RHOA	0.002	0.091	-10000	0	-0.45	12	12
cell motility	0.015	0.085	0.35	1	-0.41	7	8
PRL-1/alpha Tubulin	-0.027	0.078	-10000	0	-0.46	3	3
PRL-3/alpha1 Integrin	0.032	0.059	-10000	0	-0.32	11	11
ROCK1	0.019	0.081	0.35	1	-0.41	7	8
RABGGTB	0.035	0.007	-10000	0	-10000	0	0
CDK2	0.033	0.029	-10000	0	-0.42	2	2
mitosis	-0.027	0.082	-10000	0	-0.48	3	3
ATF5	0.033	0.022	-10000	0	-0.42	1	1

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.025	0.061	0.42	9	-10000	0	9
PI3K Class IB/PDE3B	0.025	0.061	-10000	0	-0.42	9	9
PDE3B	0.025	0.061	-10000	0	-0.42	9	9

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.067	0.058	-10000	0	-0.26	9	9
MAP4K1	0.035	0.007	-10000	0	-10000	0	0
MAP3K8	0.003	0.11	-10000	0	-0.42	32	32
PRKCB	0	0	-10000	0	-10000	0	0
DBNL	0.033	0.029	-10000	0	-0.42	2	2
CRKL	0.03	0.041	-10000	0	-0.42	4	4
MAP3K1	0.004	0.07	-10000	0	-0.31	5	5
JUN	-0.01	0.098	-10000	0	-0.51	10	10
MAP3K7	0.013	0.062	0.21	4	-0.31	6	10
GRAP2	0.032	0.023	-10000	0	-0.42	1	1
CRK	0.031	0.023	-10000	0	-0.42	1	1
MAP2K4	-0.005	0.084	0.21	1	-0.34	15	16
LAT	0.029	0.031	-10000	0	-0.42	2	2
LCP2	0.023	0.07	-10000	0	-0.42	12	12
MAPK8	0.008	0.081	-10000	0	-0.59	8	8
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.02	0.067	-10000	0	-0.25	15	15
LAT/GRAP2/SLP76/HPK1/HIP-55	0.078	0.062	-10000	0	-0.25	9	9

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	0.035	0.007	-9999	-10000	0	0
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.032	0.011	-9999	-10000	0	0
TCEB1	0.028	0.025	-9999	-0.42	1	1
HIF1A/p53	0.006	0.097	-9999	-0.27	24	24
HIF1A	-0.001	0.081	-9999	-0.28	16	16
COPS5	0.026	0.042	-9999	-0.42	4	4
VHL/Elongin B/Elongin C/RBX1/CUL2	0.071	0.052	-9999	-0.22	1	1
FIH (dimer)	0.035	0.005	-9999	-10000	0	0
CDKN2A	0.015	0.075	-9999	-0.42	14	14
ARNT/IPAS	0.05	0.013	-9999	-10000	0	0
HIF1AN	0.035	0.005	-9999	-10000	0	0
GNB2L1	0.033	0.035	-9999	-0.42	3	3
HIF1A/ARNT	0.018	0.087	-9999	-0.27	16	16
CUL2	0.035	0.007	-9999	-10000	0	0
OS9	0.034	0.029	-9999	-0.42	2	2
RACK1/Elongin B/Elongin C	0.053	0.038	-9999	-0.26	2	2
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.004	0.076	-9999	-0.27	16	16
PHD1-3/OS9	0.032	0.1	-9999	-0.24	49	49
HIF1A/RACK1/Elongin B/Elongin C	0.035	0.083	-9999	-0.26	11	11
VHL	0.035	0.007	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
HIF1A/JAB1	0.013	0.08	-9999	-0.27	13	13
EGLN3	-0.016	0.14	-9999	-0.42	52	52
EGLN2	0.031	0.041	-9999	-0.42	4	4
EGLN1	0.021	0.055	-9999	-0.42	7	7
TP53	0.008	0.1	-9999	-0.42	26	26
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.037	0.06	-9999	-0.44	4	4
ARNT	0.035	0.006	-9999	-10000	0	0
ARD1A	0.036	0.003	-9999	-10000	0	0
RBX1	0.034	0.009	-9999	-10000	0	0
HIF1A/p19ARF	0.004	0.092	-9999	-0.29	20	20

×

Insulin-mediated glucose transport

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.026	0.1	0.21	2	-0.24	40	42
CaM/Ca2+	0.026	0.005	-10000	0	-10000	0	0
AKT1	0.032	0.036	-10000	0	-0.42	3	3
AKT2	0.035	0.005	-10000	0	-10000	0	0
STXBP4	0.03	0.037	-10000	0	-0.42	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.007	0.1	0.2	3	-0.25	42	45
YWHAZ	0.026	0.016	-10000	0	-10000	0	0
CALM1	0.035	0.007	-10000	0	-10000	0	0
YWHAQ	0.033	0.029	-10000	0	-0.42	2	2
TBC1D4	0.008	0.044	-10000	0	-0.3	10	10
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.031	0.036	-10000	0	-0.42	3	3
YWHAB	0.034	0.009	-10000	0	-10000	0	0
SNARE/Synip	0.037	0.032	-10000	0	-0.25	4	4
YWHAG	0.035	0.005	-10000	0	-10000	0	0
ASIP	0	0	-10000	0	-10000	0	0
PRKCI	0.024	0.067	-10000	0	-0.42	11	11
AS160/CaM/Ca2+	0.026	0.005	-10000	0	-10000	0	0
RHOQ	0.033	0.035	-10000	0	-0.42	3	3
GYS1	0.017	0.042	0.25	12	-0.24	3	15
PRKCZ	0	0	-10000	0	-10000	0	0
TRIP10	0.032	0.041	-10000	0	-0.42	4	4
TC10/GTP/CIP4/Exocyst	0.043	0.036	-10000	0	-0.25	7	7
AS160/14-3-3	0.018	0.074	-10000	0	-0.27	11	11
VAMP2	0.031	0.023	-10000	0	-0.42	1	1
SLC2A4	0.005	0.11	0.2	3	-0.28	42	45
STX4	0	0	-10000	0	-10000	0	0
GSK3B	0.024	0.025	-10000	0	-0.28	3	3
SFN	0.011	0.099	-10000	0	-0.42	25	25
LNPEP	0.032	0.03	-10000	0	-0.42	2	2
YWHAE	0.032	0.011	-10000	0	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.028	0.054	-10000	0	-0.42	7	7
SMAD2	-0.001	0.059	0.21	2	-0.22	12	14
SMAD3	0.019	0.059	0.28	1	-0.25	5	6
SMAD3/SMAD4	0.03	0.089	-10000	0	-0.38	17	17
SMAD4/Ubc9/PIASy	0.054	0.052	-10000	0	-0.26	10	10
SMAD2/SMAD2/SMAD4	0.05	0.08	-10000	0	-0.26	4	4
PPM1A	0.034	0.022	-10000	0	-0.42	1	1
CALM1	0.035	0.007	-10000	0	-10000	0	0
SMAD2/SMAD4	0.013	0.067	-10000	0	-0.21	21	21
MAP3K1	0.01	0.099	-10000	0	-0.42	25	25
TRAP-1/SMAD4	0.046	0.043	-10000	0	-0.3	7	7
MAPK3	0.032	0.023	-10000	0	-0.42	1	1
MAPK1	0.033	0.022	-10000	0	-0.42	1	1
NUP214	0.035	0.021	-10000	0	-0.42	1	1
CTDSP1	0.034	0.029	-10000	0	-0.42	2	2
CTDSP2	0.034	0.029	-10000	0	-0.42	2	2
CTDSPL	0.028	0.054	-10000	0	-0.42	7	7
KPNB1	0.031	0.041	-10000	0	-0.42	4	4
TGFBRAP1	0.036	0.004	-10000	0	-10000	0	0
UBE2I	0.032	0.011	-10000	0	-10000	0	0
NUP153	0.035	0.007	-10000	0	-10000	0	0
KPNA2	0.023	0.061	-10000	0	-0.42	9	9
PIAS4	0.032	0.036	-10000	0	-0.42	3	3

×

Ephrin A reverse signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.041	0.037	-10000	0	-0.25	7	7
EFNA5	0.029	0.046	-10000	0	-0.42	5	5
FYN	0.011	0.041	0.19	2	-0.23	13	15
neuron projection morphogenesis	0.041	0.037	-10000	0	-0.25	7	7
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.041	0.037	-10000	0	-0.25	7	7
EPHA5	0.034	0.029	-10000	0	-0.42	2	2

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.029	0.024	-10000	0	-0.42	1	1
CLTC	0.025	0.062	0.26	2	-0.42	6	8
calcium ion-dependent exocytosis	0.017	0.038	-10000	0	-0.22	5	5
Dynamin 2/GTP	0.031	0.02	-10000	0	-0.23	2	2
EXOC4	0.034	0.021	-10000	0	-0.42	1	1
CD59	0.016	0.049	-10000	0	-0.36	5	5
CPE	-0.008	0.079	-10000	0	-0.26	43	43
CTNNB1	0.024	0.067	-10000	0	-0.42	11	11
membrane fusion	0.013	0.033	-10000	0	-0.23	4	4
CTNND1	-0.002	0.055	0.2	31	-0.22	3	34
DNM2	0.035	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.018	0.046	0.19	2	-0.27	5	7
TSHR	0.013	0.034	-10000	0	-0.25	8	8
INS	0.008	0.093	-10000	0	-0.46	18	18
BIN1	0.034	0.029	-10000	0	-0.42	2	2
mol:Choline	0.013	0.033	-10000	0	-0.23	4	4
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.015	0.018	-10000	0	-0.25	2	2
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.033	0.029	-10000	0	-0.42	2	2
mol:Ca2+	0.03	0.02	-10000	0	-0.23	2	2
JUP	0.019	0.053	-10000	0	-0.37	5	5
ASAP2/amphiphysin II	0.042	0.026	-10000	0	-0.23	4	4
ARF6/GTP	0.025	0.021	-10000	0	-0.3	2	2
CDH1	-0.003	0.069	-10000	0	-0.42	5	5
clathrin-independent pinocytosis	0.024	0.021	-10000	0	-0.3	2	2
MAPK8IP3	0.023	0.064	-10000	0	-0.42	10	10
positive regulation of endocytosis	0.024	0.021	-10000	0	-0.3	2	2
EXOC2	0.029	0.05	-10000	0	-0.42	6	6
substrate adhesion-dependent cell spreading	0.017	0.075	-10000	0	-0.33	4	4
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.032	0.022	-10000	0	-0.42	1	1
regulation of calcium-dependent cell-cell adhesion	-0.029	0.085	0.4	5	-10000	0	5
positive regulation of phagocytosis	0.015	0.021	-10000	0	-0.25	3	3
ARF6/GTP/JIP3	0.035	0.048	-10000	0	-0.25	12	12
ACAP1	0.013	0.032	-10000	0	-0.19	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.016	0.045	-10000	0	-0.35	5	5
clathrin heavy chain/ACAP1	0.023	0.062	0.28	3	-0.31	7	10
JIP4/KLC1	0.04	0.025	-10000	0	-0.23	3	3
EXOC1	0.035	0.005	-10000	0	-10000	0	0
exocyst	0.017	0.075	-10000	0	-0.33	4	4
RALA/GTP	0.026	0.005	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.042	0.027	-10000	0	-0.25	3	3
receptor recycling	0.024	0.021	-10000	0	-0.3	2	2
CTNNA1	-0.001	0.054	0.2	31	-0.22	2	33
NME1	0.015	0.018	-10000	0	-0.25	2	2
clathrin coat assembly	0.027	0.068	0.26	3	-0.4	7	10
IL2RA	0.009	0.067	-10000	0	-0.37	5	5
VAMP3	0.015	0.021	-10000	0	-0.25	3	3
GLUT4/clathrin heavy chain/ACAP1	0.03	0.06	-10000	0	-0.32	5	5
EXOC6	0.01	0.1	-10000	0	-0.42	28	28
PLD1	0.011	0.039	-10000	0	-0.28	8	8
PLD2	0.014	0.024	-10000	0	-0.2	5	5
EXOC5	0.034	0.021	-10000	0	-0.42	1	1
PIP5K1C	0.015	0.042	0.19	2	-0.27	5	7
SDC1	0.003	0.068	-10000	0	-0.43	5	5
ARF6/GDP	0.029	0.02	-10000	0	-0.25	2	2
EXOC7	0.033	0.01	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.032	0.088	-10000	0	-0.41	5	5
mol:Phosphatidic acid	0.013	0.033	-10000	0	-0.23	4	4
endocytosis	-0.04	0.026	0.23	4	-10000	0	4
SCAMP2	0.033	0.03	-10000	0	-0.42	2	2
ADRB2	0.01	0.087	0.26	1	-0.42	9	10
EXOC3	0.036	0.002	-10000	0	-10000	0	0
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.038	0.028	0.18	9	-0.23	2	11
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	0.021	0.067	0.25	3	-0.38	7	10
RALA	0.035	0.007	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.023	0.085	-10000	0	-0.39	5	5

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.041	0.057	-9999	-0.3	13	13
FBXW11	0.034	0.021	-9999	-0.42	1	1
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.034	0.021	-9999	-0.42	1	1
CHUK	0.025	0.067	-9999	-0.42	11	11
NF kappa B2 p100/RelB	0.082	0.074	-9999	-0.24	19	19
NFKB1	0.035	0.005	-9999	-10000	0	0
MAP3K14	0.032	0.03	-9999	-0.42	2	2
NF kappa B1 p50/RelB	0.046	0.04	-9999	-0.3	6	6
RELB	0.029	0.05	-9999	-0.42	6	6
NFKB2	0.034	0.021	-9999	-0.42	1	1
NF kappa B2 p52/RelB	0.042	0.036	-9999	-0.25	7	7
regulation of B cell activation	0.041	0.036	-9999	-0.25	7	7

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.036	0.023	-10000	0	-0.42	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.046	0.1	0.26	12	-0.28	6	18
ERC1	0	0	-10000	0	-10000	0	0
RIP2/NOD2	0.02	0.011	-10000	0	-10000	0	0
NFKBIA	0.011	0.036	-10000	0	-0.37	3	3
BIRC2	0.031	0.012	-10000	0	-10000	0	0
IKBKB	0.029	0.014	-10000	0	-10000	0	0
RIPK2	0.028	0.015	-10000	0	-10000	0	0
IKBKG	0.01	0.098	-10000	0	-0.34	19	19
IKK complex/A20	0.033	0.12	-10000	0	-0.4	5	5
NEMO/A20/RIP2	0.028	0.015	-10000	0	-10000	0	0
XPO1	0.035	0.005	-10000	0	-10000	0	0
NEMO/ATM	0.022	0.11	-10000	0	-0.32	20	20
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.035	0.005	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.047	0.01	-10000	0	-10000	0	0
IKK complex/ELKS	0.011	0.1	-10000	0	-0.32	18	18
BCL10/MALT1/TRAF6	0.063	0.041	-10000	0	-0.31	4	4
NOD2	0	0	-10000	0	-10000	0	0
NFKB1	0.037	0.011	-10000	0	-10000	0	0
RELA	0.036	0.011	-10000	0	-10000	0	0
MALT1	0.031	0.041	-10000	0	-0.42	4	4
cIAP1/UbcH5C	0.046	0.019	-10000	0	-10000	0	0
ATM	0.031	0.013	-10000	0	-10000	0	0
TNF/TNFR1A	0.043	0.048	-10000	0	-0.3	9	9
TRAF6	0.034	0.021	-10000	0	-0.42	1	1
PRKCA	0.031	0.012	-10000	0	-10000	0	0
CHUK	0.025	0.067	-10000	0	-0.42	11	11
UBE2D3	0.035	0.005	-10000	0	-10000	0	0
TNF	0.026	0.061	-10000	0	-0.42	9	9
NF kappa B1 p50/RelA	0.074	0.034	-10000	0	-0.24	3	3
BCL10	0.034	0.008	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.011	0.036	0.21	4	-0.37	3	7
beta TrCP1/SCF ubiquitin ligase complex	0.036	0.023	-10000	0	-0.42	1	1
TNFRSF1A	0.033	0.022	-10000	0	-0.42	1	1
IKK complex	0.023	0.12	-10000	0	-0.34	18	18
CYLD	0.029	0.024	-10000	0	-0.42	1	1
IKK complex/PKC alpha	0.028	0.11	-10000	0	-0.41	3	3

×

Circadian rhythm 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
chromatin modification	0.035	0.087	-10000	0	-1.2	1	1
CLOCK	0.037	0.022	-10000	0	-0.42	1	1
TIMELESS/CRY2	0.042	0.061	-10000	0	-1.2	1	1
DEC1/BMAL1	0.043	0.061	-10000	0	-0.32	13	13
ATR	0.035	0.006	-10000	0	-10000	0	0
NR1D1	0.022	0.024	-10000	0	-10000	0	0
ARNTL	0.029	0.061	-10000	0	-0.42	9	9
TIMELESS	0.022	0.059	-10000	0	-1.3	1	1
NPAS2	0.027	0.064	-10000	0	-0.42	10	10
CRY2	0.035	0.005	-10000	0	-10000	0	0
mol:CO	-0.01	0.006	0.14	1	-10000	0	1
CHEK1	0	0.11	-10000	0	-0.42	31	31
mol:HEME	0.01	0.006	-10000	0	-0.14	1	1
PER1	0.031	0.012	-10000	0	-10000	0	0
BMAL/CLOCK/NPAS2	0.067	0.069	-10000	0	-0.26	19	19
BMAL1/CLOCK	0.026	0.077	-10000	0	-0.49	3	3
S phase of mitotic cell cycle	0.035	0.087	-10000	0	-1.2	1	1
TIMELESS/CHEK1/ATR	0.035	0.089	-10000	0	-1.3	1	1
mol:NADPH	0.01	0.006	-10000	0	-0.14	1	1
PER1/TIMELESS	0.038	0.06	-10000	0	-1.2	1	1
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.031	0.046	-10000	0	-0.42	5	5

×

Aurora C signaling

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
INCENP	0.028	0.054	-9999	-0.42	7	7
Aurora C/Aurora B/INCENP	0.052	0.049	-9999	-0.23	11	11
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.012	0.03	-9999	-0.4	2	2
AURKB	0.029	0.037	-9999	-0.42	3	3
AURKC	0.034	0.021	-9999	-0.42	1	1

×

Signaling events mediated by HDAC Class I

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.072	0.069	-10000	0	-0.29	9	9
Ran/GTP/Exportin 1/HDAC1	-0.013	0.009	-10000	0	-0.2	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.043	0.075	-10000	0	-0.3	10	10
SUMO1	0.036	0.004	-10000	0	-10000	0	0
ZFPM1	0.022	0.055	-10000	0	-0.42	7	7
NPC/RanGAP1/SUMO1/Ubc9	0.016	0.011	-10000	0	-0.17	1	1
FKBP3	0.032	0.036	-10000	0	-0.42	3	3
Histones	0.071	0.062	-10000	0	-0.31	2	2
YY1/LSF	0.03	0.059	-10000	0	-0.23	13	13
SMG5	0	0	-10000	0	-10000	0	0
RAN	0.035	0.005	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.027	0.039	-10000	0	-0.24	9	9
I kappa B alpha/HDAC1	0.041	0.054	-10000	0	-0.31	5	5
SAP18	0.033	0.01	-10000	0	-10000	0	0
RELA	0.019	0.057	0.28	1	-0.25	7	8
HDAC1/Smad7	0.067	0.028	-10000	0	-0.25	2	2
RANGAP1	0.032	0.022	-10000	0	-0.42	1	1
HDAC3/TR2	0.039	0.056	-10000	0	-0.25	9	9
NuRD/MBD3 Complex	0.031	0.066	-10000	0	-0.34	7	7
NF kappa B1 p50/RelA	0.037	0.072	0.25	1	-0.36	3	4
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.029	0.046	-10000	0	-0.42	5	5
GATA1	0.036	0	-10000	0	-10000	0	0
Mad/Max	0.051	0.012	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.017	0.092	-10000	0	-0.4	11	11
RBBP7	0.034	0.029	-10000	0	-0.42	2	2
NPC	0.021	0.002	-10000	0	-10000	0	0
RBBP4	0.034	0.021	-10000	0	-0.42	1	1
MAX	0.035	0.007	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.034	0.021	-10000	0	-0.42	1	1
NFKBIA	0.022	0.042	-10000	0	-0.37	4	4
KAT2B	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.021	0.057	-10000	0	-0.33	5	5
SIN3 complex	0.076	0.045	-10000	0	-0.23	5	5
SMURF1	0.035	0.006	-10000	0	-10000	0	0
CHD3	0.031	0.023	-10000	0	-0.42	1	1
SAP30	0.03	0.046	-10000	0	-0.42	5	5
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.032	0.011	-10000	0	-10000	0	0
YY1/HDAC3	0.029	0.05	-10000	0	-0.35	2	2
YY1/HDAC2	0.034	0.045	-10000	0	-0.22	4	4
YY1/HDAC1	0.036	0.046	-10000	0	-0.25	3	3
NuRD/MBD2 Complex (MeCP1)	0.031	0.066	-10000	0	-0.34	6	6
PPARG	0.011	0.092	0.3	1	-0.36	23	24
HDAC8/hEST1B	0.047	0.02	-10000	0	-0.25	2	2
UBE2I	0.032	0.011	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.034	0.021	-10000	0	-0.42	1	1
TNFRSF1A	0.033	0.022	-10000	0	-0.42	1	1
HDAC3/SMRT (N-CoR2)	0.042	0.048	-10000	0	-0.33	2	2
MBD3L2	0.028	0.057	-10000	0	-0.42	8	8
ubiquitin-dependent protein catabolic process	0.066	0.027	-10000	0	-0.25	2	2
CREBBP	0.032	0.011	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.034	0.08	-10000	0	-0.38	6	6
HDAC1	0.034	0.021	-10000	0	-0.42	1	1
HDAC3	0.025	0.029	-10000	0	-0.33	1	1
HDAC2	0.032	0.023	-10000	0	-0.42	1	1
YY1	0.016	0.014	-10000	0	-0.24	1	1
HDAC8	0.034	0.029	-10000	0	-0.42	2	2
SMAD7	0.034	0.021	-10000	0	-0.42	1	1
NCOR2	0.036	0.004	-10000	0	-10000	0	0
MXD1	0.035	0.005	-10000	0	-10000	0	0
STAT3	0.019	0.027	-10000	0	-0.36	2	2
NFKB1	0.035	0.005	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.036	0.004	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.048	0.061	-10000	0	-0.22	13	13
YY1/SAP30/HDAC1	0.049	0.058	-10000	0	-0.26	8	8
EP300	0.033	0.022	-10000	0	-0.42	1	1
STAT3 (dimer non-phopshorylated)	0.019	0.027	-10000	0	-0.36	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.022	0.042	-10000	0	-0.37	4	4
histone deacetylation	0.031	0.065	-10000	0	-0.34	6	6
STAT3 (dimer non-phopshorylated)/HDAC3	0.023	0.056	-10000	0	-0.38	4	4
nuclear export	-0.046	0.02	0.25	2	-10000	0	2
PRKACA	0.036	0.004	-10000	0	-10000	0	0
GATAD2B	0.027	0.025	-10000	0	-0.42	1	1
GATAD2A	0.035	0.006	-10000	0	-10000	0	0
GATA2/HDAC3	0.04	0.049	-10000	0	-0.26	5	5
GATA1/HDAC1	0.051	0.018	-10000	0	-0.3	1	1
GATA1/HDAC3	0.043	0.048	-10000	0	-0.34	2	2
CHD4	0.033	0.022	-10000	0	-0.42	1	1
TNF-alpha/TNFR1A	0.043	0.048	-10000	0	-0.3	9	9
SIN3/HDAC complex/Mad/Max	0.024	0.06	-10000	0	-0.32	6	6
NuRD Complex	0.036	0.076	-10000	0	-0.37	6	6
positive regulation of chromatin silencing	0.067	0.06	-10000	0	-0.3	2	2
SIN3B	0.035	0.005	-10000	0	-10000	0	0
MTA2	0.033	0.03	-10000	0	-0.42	2	2
SIN3A	0.035	0.007	-10000	0	-10000	0	0
XPO1	0.035	0.005	-10000	0	-10000	0	0
SUMO1/HDAC1	0.052	0.044	-10000	0	-0.26	2	2
HDAC complex	0.08	0.042	-10000	0	-0.24	5	5
GATA1/Fog1	0.037	0.046	-10000	0	-0.3	7	7
FKBP25/HDAC1/HDAC2	0.061	0.04	-10000	0	-0.26	5	5
TNF	0.026	0.061	-10000	0	-0.42	9	9
negative regulation of cell growth	0.024	0.059	-10000	0	-0.32	6	6
NuRD/MBD2/PRMT5 Complex	0.031	0.066	-10000	0	-0.34	6	6
Ran/GTP/Exportin 1	0.053	0.042	-10000	0	-0.24	1	1
NF kappa B/RelA/I kappa B alpha	0.021	0.065	-10000	0	-0.31	11	11
SIN3/HDAC complex/NCoR1	0.016	0.06	-10000	0	-0.28	9	9
TFCP2	0.027	0.064	-10000	0	-0.42	10	10
NR2C1	0.029	0.054	-10000	0	-0.42	7	7
MBD3	0.034	0.008	-10000	0	-10000	0	0
MBD2	0.035	0.007	-10000	0	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.015	0.039	0.16	5	-0.18	1	6
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.021	0.042	0.17	5	-0.21	2	7
AP2	0.046	0.034	-10000	0	-0.3	4	4
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.042	0.035	-10000	0	-0.24	7	7
CLTB	0.033	0.029	-10000	0	-0.42	2	2
coatomer protein complex/ARF1/GTP/ER cargo protein	0.016	0.022	-10000	0	-0.22	3	3
CD4	0.034	0.009	-10000	0	-10000	0	0
CLTA	0.035	0.006	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-10000	0	0
ARFGAP1	0.008	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.019	0.033	0.17	5	-0.13	2	7
ARF1/GTP	0.016	0.017	-10000	0	-0.25	1	1
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.021	0.045	0.17	37	-0.19	1	38
mol:Choline	0.019	0.033	0.18	5	-0.14	2	7
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.028	0.026	-10000	0	-0.43	1	1
DDEF1	0.014	0.029	0.16	3	-0.17	1	4
ARF1/GDP	0.001	0.021	-10000	0	-0.11	6	6
AP2M1	0.031	0.041	-10000	0	-0.42	4	4
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.011	0.013	-10000	0	-0.23	1	1
Rac/GTP	0.028	0.006	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.032	0.027	-10000	0	-0.22	1	1
ARFIP2	0.02	0.053	-10000	0	-0.39	7	7
COPA	0.029	0.015	-10000	0	-10000	0	0
RAC1	0.035	0.006	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.015	0.028	-10000	0	-0.19	2	2
ARF1/GTP/ARHGAP10	0.018	0.016	-10000	0	-0.25	1	1
GGA3	0.032	0.023	-10000	0	-0.42	1	1
ARF1/GTP/Membrin	0.016	0.046	-10000	0	-0.24	13	13
AP2A1	0.035	0.007	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.01	0.029	-10000	0	-0.22	4	4
ARF1/GDP/Membrin	0.015	0.052	-10000	0	-0.27	14	14
Arfaptin 2/Rac/GDP	0.039	0.037	-10000	0	-0.25	7	7
CYTH2	-0.001	0.003	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.033	0.026	-10000	0	-0.26	1	1
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.026	0.004	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.023	0.04	-10000	0	-0.4	2	2
PLD2	0.019	0.033	0.18	5	-0.14	2	7
ARF-GAP1/v-SNARE	0.008	0.003	-10000	0	-10000	0	0
PIP5K1A	0.019	0.033	0.17	5	-0.13	2	7
ARF1/GTP/Membrin/GBF1/p115	0.013	0.025	-10000	0	-0.22	1	1
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.019	0.033	0.18	5	-0.14	2	7
KDEL Receptor/Ligand/ARF-GAP1	0.008	0.003	-10000	0	-10000	0	0
GOSR2	0.018	0.038	-10000	0	-0.32	5	5
USO1	0.009	0.017	0.091	5	-0.063	2	7
GBF1	0.019	0.036	-10000	0	-0.32	4	4
ARF1/GTP/Arfaptin 2	0.034	0.032	-10000	0	-0.25	3	3
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.06	0.038	-10000	0	-0.26	4	4

×

Rapid glucocorticoid signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.055	0.04	-10000	0	-0.24	7	7
MAPK9	-0.002	0.057	-10000	0	-0.29	19	19
adrenocorticotropin secretion	0.005	0.024	-10000	0	-0.3	3	3
GNB1/GNG2	0.044	0.034	-10000	0	-0.25	6	6
GNB1	0.032	0.045	-10000	0	-0.42	5	5
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	0.009	0.001	-10000	0	-10000	0	0
Gs family/GTP	0.02	0.02	-10000	0	-0.22	3	3
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	0.002	0.005	0.062	3	-10000	0	3
GNAL	0.031	0.036	-10000	0	-0.42	3	3
GNG2	0.034	0.021	-10000	0	-0.42	1	1
CRH	0.026	0.038	-10000	0	-0.42	3	3
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.008	0.023	-10000	0	-0.29	3	3
MAPK11	0.009	0.003	-10000	0	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.034	0.021	-10000	0	-0.42	1	1
Ran/GTP/Exportin 1/HDAC4	0.006	0.014	-10000	0	-0.18	1	1
MDM2/SUMO1	0.05	0.042	-10000	0	-10000	0	0
HDAC4	0.034	0.021	-10000	0	-0.42	1	1
Ran/GTP/Exportin 1/HDAC1	0.006	0.015	-10000	0	-0.21	1	1
SUMO1	0.036	0.004	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1	0.013	0.02	-10000	0	-0.25	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	0.006	0.024	-10000	0	-0.26	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.035	0.005	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.036	0.004	-10000	0	-10000	0	0
SUMO1/HDAC4	0.051	0.044	-10000	0	-0.21	2	2
SUMO1/HDAC1	0.052	0.044	-10000	0	-0.26	2	2
RANGAP1	0.032	0.022	-10000	0	-0.42	1	1
MDM2/SUMO1/SUMO1	0.08	0.036	-10000	0	-0.24	2	2
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.016	0.011	-10000	0	-0.17	1	1
Ran/GTP	0.036	0.039	-10000	0	-0.2	2	2
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.034	0.009	-10000	0	-10000	0	0
UBE2I	0.032	0.011	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.035	0.041	0.21	6	-0.24	1	7
NPC	0.021	0.002	-10000	0	-10000	0	0
PIAS2	0.033	0.03	-10000	0	-0.42	2	2
PIAS1	0.035	0.006	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0