Breast Invasive Carcinoma: PARADIGM pathway analysis of mRNA expression data

Pathway.Name	Avg.Num.Perturbations
Signaling events regulated by Ret tyrosine kinase	115
Signaling events mediated by Stem cell factor receptor (c-Kit)	113
FOXM1 transcription factor network	92
Syndecan-1-mediated signaling events	91
IGF1 pathway	85
Wnt signaling	83
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	83
Endothelins	82
EGFR-dependent Endothelin signaling events	82
HIF-1-alpha transcription factor network	76

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	115	9443	82	-0.23	0.018	1000	-1000	-0.053	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	113	8848	78	-0.39	0.17	1000	-1000	-0.038	-1000
FOXM1 transcription factor network	92	4708	51	-0.43	0.024	1000	-1000	-0.11	-1000
Syndecan-1-mediated signaling events	91	3097	34	-0.19	0.018	1000	-1000	-0.014	-1000
IGF1 pathway	85	4876	57	-0.14	0.057	1000	-1000	-0.054	-1000
Wnt signaling	83	582	7	-0.13	-0.011	1000	-1000	-0.011	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	83	5658	68	-0.43	0.22	1000	-1000	-0.067	-1000
Endothelins	82	7915	96	-0.25	0.018	1000	-1000	-0.041	-1000
EGFR-dependent Endothelin signaling events	82	1742	21	-0.17	0.024	1000	-1000	-0.047	-1000
HIF-1-alpha transcription factor network	76	5835	76	-0.25	0.025	1000	-1000	-0.057	-1000
Fc-epsilon receptor I signaling in mast cells	76	7379	97	-0.15	0.038	1000	-1000	-0.051	-1000
Plasma membrane estrogen receptor signaling	74	6417	86	-0.2	0.19	1000	-1000	-0.057	-1000
FAS signaling pathway (CD95)	70	3295	47	-0.16	0.072	1000	-1000	-0.027	-1000
IL6-mediated signaling events	70	5301	75	-0.18	0.043	1000	-1000	-0.03	-1000
TCGA08_retinoblastoma	70	562	8	-0.052	0.026	1000	-1000	-0.004	-1000
IL4-mediated signaling events	68	6261	91	-0.52	0.39	1000	-1000	-0.11	-1000
IL27-mediated signaling events	67	3439	51	-0.27	0.17	1000	-1000	-0.045	-1000
Glucocorticoid receptor regulatory network	66	7604	114	-0.54	0.28	1000	-1000	-0.046	-1000
TCR signaling in naïve CD8+ T cells	66	6170	93	-0.13	0.07	1000	-1000	-0.045	-1000
IL12-mediated signaling events	62	5415	87	-0.3	0.029	1000	-1000	-0.083	-1000
Noncanonical Wnt signaling pathway	62	1636	26	-0.13	0.018	1000	-1000	-0.023	-1000
Osteopontin-mediated events	58	2234	38	-0.15	0.018	1000	-1000	-0.027	-1000
IL23-mediated signaling events	58	3489	60	-0.27	0.017	1000	-1000	-0.096	-1000
Arf6 signaling events	57	3584	62	-0.15	0.034	1000	-1000	-0.013	-1000
Thromboxane A2 receptor signaling	55	5871	105	-0.14	0.038	1000	-1000	-0.046	-1000
Nongenotropic Androgen signaling	54	2812	52	-0.13	0.064	1000	-1000	-0.034	-1000
PLK2 and PLK4 events	49	149	3	-0.049	0.008	1000	-1000	-0.004	-1000
Stabilization and expansion of the E-cadherin adherens junction	49	3674	74	-0.14	0.03	1000	-1000	-0.059	-1000
E-cadherin signaling events	49	249	5	-0.049	0.011	1000	-1000	-0.002	-1000
Syndecan-4-mediated signaling events	48	3265	67	-0.08	0.022	1000	-1000	-0.022	-1000
Signaling events mediated by the Hedgehog family	46	2434	52	-0.16	0.056	1000	-1000	-0.024	-1000
BMP receptor signaling	46	3778	81	-0.23	0.046	1000	-1000	-0.061	-1000
ErbB4 signaling events	44	3049	69	-0.17	0.097	1000	-1000	-0.064	-1000
IL2 signaling events mediated by PI3K	43	2540	58	-0.23	0.018	1000	-1000	-0.049	-1000
amb2 Integrin signaling	41	3427	82	-0.12	0.023	1000	-1000	-0.043	-1000
Ephrin B reverse signaling	41	2002	48	-0.14	0.021	1000	-1000	-0.041	-1000
LPA receptor mediated events	41	4267	102	-0.13	0.018	1000	-1000	-0.049	-1000
BCR signaling pathway	41	4142	99	-0.16	0.043	1000	-1000	-0.055	-1000
Caspase cascade in apoptosis	40	2970	74	-0.085	0.044	1000	-1000	-0.022	-1000
Syndecan-2-mediated signaling events	39	2696	69	-0.072	0.022	1000	-1000	-0.027	-1000
TCGA08_p53	39	277	7	-0.037	0.028	1000	-1000	-0.003	-1000
Signaling events mediated by PTP1B	37	2848	76	-0.15	0.055	1000	-1000	-0.047	-1000
Integrins in angiogenesis	37	3151	84	-0.18	0.031	1000	-1000	-0.058	-1000
Canonical Wnt signaling pathway	37	1906	51	-0.25	0.098	1000	-1000	-0.025	-1000
Calcium signaling in the CD4+ TCR pathway	36	1146	31	-0.14	0.026	1000	-1000	-0.034	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	35	1607	45	-0.13	0.018	1000	-1000	-0.057	-1000
Visual signal transduction: Rods	35	1868	52	-0.1	0.027	1000	-1000	-0.052	-1000
Ras signaling in the CD4+ TCR pathway	35	611	17	-0.038	0.013	1000	-1000	-0.006	-1000
IL1-mediated signaling events	34	2135	62	-0.082	0.051	1000	-1000	-0.052	-1000
Glypican 2 network	34	138	4	-0.016	0	1000	-1000	-0.002	-1000
Coregulation of Androgen receptor activity	33	2561	76	-0.18	0.029	1000	-1000	-0.015	-1000
Glypican 1 network	33	1618	48	-0.064	0.017	1000	-1000	-0.024	-1000
Signaling mediated by p38-gamma and p38-delta	33	504	15	-0.07	0.014	1000	-1000	-0.011	-1000
Class IB PI3K non-lipid kinase events	33	99	3	-0.004	-1000	1000	-1000	-0.001	-1000
Regulation of nuclear SMAD2/3 signaling	32	4415	136	-0.2	0.066	1000	-1000	-0.025	-1000
TRAIL signaling pathway	32	1581	48	-0.05	0.018	1000	-1000	-0.052	-1000
E-cadherin signaling in the nascent adherens junction	32	2487	76	-0.078	0.024	1000	-1000	-0.051	-1000
Presenilin action in Notch and Wnt signaling	31	1942	61	-0.22	0.036	1000	-1000	-0.036	-1000
Syndecan-3-mediated signaling events	31	1104	35	-0.099	0.033	1000	-1000	-0.026	-1000
Nectin adhesion pathway	30	1946	63	-0.11	0.024	1000	-1000	-0.051	-1000
Reelin signaling pathway	30	1695	56	-0.089	0.038	1000	-1000	-0.048	-1000
Visual signal transduction: Cones	29	1108	38	-0.072	0.025	1000	-1000	-0.005	-1000
Cellular roles of Anthrax toxin	29	1169	39	-0.14	0.018	1000	-1000	-0.015	-1000
PDGFR-alpha signaling pathway	29	1307	44	-0.18	0.028	1000	-1000	-0.011	-1000
Regulation of Telomerase	28	2899	102	-0.2	0.044	1000	-1000	-0.073	-1000
IFN-gamma pathway	27	1843	68	-0.086	0.023	1000	-1000	-0.054	-1000
IL2 signaling events mediated by STAT5	27	594	22	-0.073	0.021	1000	-1000	-0.016	-1000
Class I PI3K signaling events	27	2031	73	-0.089	0.031	1000	-1000	-0.03	-1000
Insulin Pathway	27	2032	74	-0.16	0.05	1000	-1000	-0.053	-1000
E-cadherin signaling in keratinocytes	27	1175	43	-0.079	0.018	1000	-1000	-0.018	-1000
p75(NTR)-mediated signaling	26	3260	125	-0.13	0.036	1000	-1000	-0.054	-1000
Ceramide signaling pathway	26	1987	76	-0.14	0.055	1000	-1000	-0.019	-1000
Aurora B signaling	26	1742	67	-0.095	0.02	1000	-1000	-0.043	-1000
RXR and RAR heterodimerization with other nuclear receptor	25	1317	52	-0.11	0.037	1000	-1000	-0.03	-1000
Effects of Botulinum toxin	25	675	26	-0.17	0.019	1000	-1000	-0.009	-1000
TCGA08_rtk_signaling	25	665	26	-0.079	0.039	1000	-1000	-0.01	-1000
FOXA2 and FOXA3 transcription factor networks	24	1132	46	-0.2	0.074	1000	-1000	-0.021	-1000
Regulation of Androgen receptor activity	23	1647	70	-0.18	0.026	1000	-1000	-0.032	-1000
Sphingosine 1-phosphate (S1P) pathway	22	625	28	-0.079	0.021	1000	-1000	-0.011	-1000
S1P1 pathway	22	817	36	-0.061	0.018	1000	-1000	-0.041	-1000
PLK1 signaling events	21	1867	85	-0.1	0.028	1000	-1000	-0.035	-1000
Atypical NF-kappaB pathway	21	681	31	-0.074	0.028	1000	-1000	-0.011	-1000
Angiopoietin receptor Tie2-mediated signaling	21	1870	88	-0.16	0.052	1000	-1000	-0.076	-1000
Arf6 downstream pathway	20	900	43	-0.022	0.019	1000	-1000	-0.027	-1000
mTOR signaling pathway	20	1092	53	-0.037	0.035	1000	-1000	-0.043	-1000
Aurora A signaling	19	1173	60	-0.037	0.034	1000	-1000	-0.01	-1000
HIF-2-alpha transcription factor network	19	855	43	-0.081	0.082	1000	-1000	-0.054	-1000
PDGFR-beta signaling pathway	19	1883	97	-0.082	0.036	1000	-1000	-0.052	-1000
Signaling events mediated by PRL	19	659	34	-0.095	0.026	1000	-1000	-0.017	-1000
EPHB forward signaling	18	1560	85	-0.039	0.038	1000	-1000	-0.057	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	18	608	33	-0.074	0.049	1000	-1000	-0.02	-1000
p38 MAPK signaling pathway	18	797	44	-0.078	0.034	1000	-1000	-0.05	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	17	956	54	-0.092	0.031	1000	-1000	-0.06	-1000
Hedgehog signaling events mediated by Gli proteins	17	1165	65	-0.051	0.041	1000	-1000	-0.048	-1000
ceramide signaling pathway	17	881	49	-0.11	0.037	1000	-1000	-0.021	-1000
Regulation of p38-alpha and p38-beta	17	969	54	-0.074	0.043	1000	-1000	-0.036	-1000
S1P3 pathway	17	745	42	-0.079	0.021	1000	-1000	-0.014	-1000
ErbB2/ErbB3 signaling events	16	1095	65	-0.059	0.024	1000	-1000	-0.044	-1000
BARD1 signaling events	16	949	57	-0.041	0.04	1000	-1000	-0.018	-1000
JNK signaling in the CD4+ TCR pathway	16	280	17	-0.036	0.029	1000	-1000	-0.018	-1000
Signaling events mediated by HDAC Class III	16	669	40	-0.077	0.034	1000	-1000	-0.023	-1000
Retinoic acid receptors-mediated signaling	16	930	58	-0.085	0.04	1000	-1000	-0.057	-1000
Signaling mediated by p38-alpha and p38-beta	16	733	44	-0.09	0.025	1000	-1000	-0.009	-1000
Signaling events mediated by VEGFR1 and VEGFR2	16	2032	125	-0.06	0.055	1000	-1000	-0.062	-1000
Neurotrophic factor-mediated Trk receptor signaling	16	2039	120	-0.12	0.053	1000	-1000	-0.047	-1000
Paxillin-independent events mediated by a4b1 and a4b7	15	567	37	-0.023	0.028	1000	-1000	-0.015	-1000
VEGFR1 specific signals	15	860	56	-0.035	0.026	1000	-1000	-0.025	-1000
LPA4-mediated signaling events	14	178	12	-0.03	0.015	1000	-1000	-0.002	-1000
a4b1 and a4b7 Integrin signaling	14	70	5	-0.007	0.018	1000	-1000	-0.007	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	14	1245	85	-0.14	0.039	1000	-1000	-0.047	-1000
EPO signaling pathway	14	792	55	-0.15	0.024	1000	-1000	-0.05	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	14	1244	83	-0.11	0.057	1000	-1000	-0.023	-1000
Signaling events mediated by HDAC Class II	12	949	75	-0.16	0.039	1000	-1000	-0.032	-1000
Paxillin-dependent events mediated by a4b1	12	432	36	-0.032	0.035	1000	-1000	-0.042	-1000
Nephrin/Neph1 signaling in the kidney podocyte	10	361	34	-0.009	0.035	1000	-1000	-0.013	-1000
Aurora C signaling	10	70	7	-0.007	0.016	1000	-1000	-0.033	-1000
FoxO family signaling	10	655	64	-0.12	0.068	1000	-1000	-0.021	-1000
Circadian rhythm pathway	9	202	22	-0.046	0.042	1000	-1000	-0.016	-1000
S1P5 pathway	9	161	17	-0.017	0.018	1000	-1000	-0.01	-1000
Alternative NF-kappaB pathway	9	117	13	0	0.034	1000	-1000	-0.005	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	8	193	23	-0.03	0.033	1000	-1000	-0.014	-1000
Canonical NF-kappaB pathway	8	342	39	-0.056	0.06	1000	-1000	-0.056	-1000
Ephrin A reverse signaling	8	60	7	0	0.015	1000	-1000	-0.007	-1000
Class I PI3K signaling events mediated by Akt	6	415	68	-0.038	0.052	1000	-1000	-0.02	-1000
Arf6 trafficking events	6	434	71	-0.021	0.031	1000	-1000	-0.046	-1000
S1P4 pathway	6	173	25	-0.017	0.021	1000	-1000	-0.013	-1000
Insulin-mediated glucose transport	5	178	32	-0.015	0.033	1000	-1000	-0.011	-1000
Signaling events mediated by HDAC Class I	5	527	104	-0.033	0.053	1000	-1000	-0.032	-1000
Rapid glucocorticoid signaling	5	117	20	-0.005	0.02	1000	-1000	-0.006	-1000
Arf1 pathway	3	164	54	-0.001	0.036	1000	-1000	-0.021	-1000
Sumoylation by RanBP2 regulates transcriptional repression	1	40	27	-0.001	0.04	1000	-1000	-0.037	-1000
Total	4443	264413	7203	-15	-990	131000	-131000	-4.5	-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.057	0.13	-9999	-0.74	13	13
Crk/p130 Cas/Paxillin	-0.17	0.18	-9999	-0.4	164	164
JUN	-0.17	0.21	-9999	-0.45	142	142
HRAS	0.012	0.051	-9999	-0.41	7	7
RET51/GFRalpha1/GDNF/GRB10	-0.21	0.22	-9999	-0.38	277	277
RAP1A	0.012	0.057	-9999	-0.52	6	6
FRS2	0.011	0.047	-9999	-0.27	13	13
RAP1A/GDP	0.009	0.041	-9999	-0.38	6	6
RET51/GFRalpha1/GDNF/DOK1	-0.21	0.22	-9999	-0.39	271	271
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.017	0.023	-9999	-0.52	1	1
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0.033	-9999	-0.52	2	2
RET9/GFRalpha1/GDNF/Enigma	-0.1	0.14	-9999	-0.28	188	188
RHOA	0.005	0.08	-9999	-0.52	12	12
RAP1A/GTP	-0.18	0.19	-9999	-0.36	245	245
GRB7	-0.017	0.1	-9999	-0.29	59	59
RET51/GFRalpha1/GDNF	-0.2	0.21	-9999	-0.38	265	265
MAPKKK cascade	-0.18	0.19	-9999	-0.45	145	145
BCAR1	0.017	0.012	-9999	-0.25	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.14	0.19	-9999	-0.35	199	199
lamellipodium assembly	-0.16	0.16	-9999	-0.33	220	220
RET51/GFRalpha1/GDNF/SHC	-0.2	0.21	-9999	-0.38	266	266
PIK3CA	0.016	0.029	-9999	-0.34	3	3
RET9/GFRalpha1/GDNF/SHC	-0.1	0.14	-9999	-0.28	189	189
RET9/GFRalpha1/GDNF/Shank3	-0.1	0.14	-9999	-0.28	190	190
MAPK3	-0.16	0.18	-9999	-0.43	135	135
DOK1	0.002	0.083	-9999	-0.41	19	19
DOK6	-0.028	0.14	-9999	-0.44	52	52
PXN	0.018	0	-9999	-10000	0	0
neurite development	-0.16	0.19	-9999	-0.41	144	144
DOK5	-0.028	0.14	-9999	-0.38	60	60
GFRA1	-0.22	0.24	-9999	-0.43	282	282
MAPK8	-0.16	0.2	-9999	-0.43	145	145
HRAS/GTP	-0.21	0.22	-9999	-0.41	242	242
tube development	-0.091	0.13	-9999	-0.26	193	193
MAPK1	-0.17	0.18	-9999	-0.43	135	135
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.079	0.12	-9999	-0.24	189	189
Rac1/GDP	0.013	0	-9999	-10000	0	0
SRC	0.015	0.035	-9999	-0.43	3	3
PDLIM7	0.017	0.012	-9999	-0.25	1	1
RET51/GFRalpha1/GDNF/Dok6	-0.2	0.23	-9999	-0.4	251	251
SHC1	0.017	0.023	-9999	-0.52	1	1
RET51/GFRalpha1/GDNF/Dok4	-0.2	0.21	-9999	-0.38	269	269
RET51/GFRalpha1/GDNF/Dok5	-0.22	0.23	-9999	-0.41	277	277
PRKCA	0.014	0.033	-9999	-0.25	8	8
HRAS/GDP	0.009	0.036	-9999	-0.29	7	7
CREB1	-0.14	0.19	-9999	-0.38	189	189
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.083	0.14	-9999	-0.25	192	192
RET51/GFRalpha1/GDNF/Grb7	-0.22	0.22	-9999	-0.4	275	275
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.18	0.23	-9999	-0.41	247	247
DOK4	0.013	0.047	-9999	-0.37	7	7
JNK cascade	-0.16	0.2	-9999	-0.44	142	142
RET9/GFRalpha1/GDNF/FRS2	-0.11	0.14	-9999	-0.28	190	190
SHANK3	0.016	0.033	-9999	-0.52	2	2
RASA1	0.004	0.078	-9999	-0.42	16	16
NCK1	0.011	0.045	-9999	-0.28	12	12
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.077	0.12	-9999	-0.23	189	189
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.16	0.19	-9999	-0.43	133	133
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.17	0.21	-9999	-0.46	143	143
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.18	0.23	-9999	-0.54	131	131
PI3K	-0.23	0.28	-9999	-0.52	219	219
SOS1	0.017	0.023	-9999	-0.52	1	1
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.09	0.14	-9999	-0.26	193	193
GRB10	-0.003	0.097	-9999	-0.43	24	24
activation of MAPKK activity	-0.13	0.16	-9999	-0.37	122	122
RET51/GFRalpha1/GDNF/FRS2	-0.2	0.21	-9999	-0.38	268	268
GAB1	0.006	0.074	-9999	-0.43	14	14
IRS1	-0.048	0.17	-9999	-0.49	68	68
IRS2	-0.026	0.13	-9999	-0.39	57	57
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.19	0.24	-9999	-0.55	136	136
RET51/GFRalpha1/GDNF/PKC alpha	-0.2	0.21	-9999	-0.38	265	265
GRB2	0.016	0.024	-9999	-0.25	4	4
PRKACA	0.018	0	-9999	-10000	0	0
GDNF	0.014	0.042	-9999	-0.45	4	4
RAC1	0.018	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.23	0.26	-9999	-0.43	274	274
Rac1/GTP	-0.19	0.2	-9999	-0.4	220	220
RET9/GFRalpha1/GDNF	-0.12	0.15	-9999	-0.32	188	188
GFRalpha1/GDNF	-0.15	0.18	-9999	-0.37	188	188

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.15	0.21	-10000	0	-0.42	163	163
CRKL	-0.16	0.22	-10000	0	-0.45	165	165
HRAS	-0.12	0.19	-10000	0	-0.38	143	143
mol:PIP3	-0.15	0.2	0.24	1	-0.42	159	160
SPRED1	-0.002	0.098	-10000	0	-0.47	21	21
SPRED2	-0.003	0.1	-10000	0	-0.5	21	21
GAB1	-0.17	0.23	-10000	0	-0.47	168	168
FOXO3	-0.14	0.2	-10000	0	-0.42	155	155
AKT1	-0.16	0.21	-10000	0	-0.44	164	164
BAD	-0.14	0.2	-10000	0	-0.41	159	159
megakaryocyte differentiation	-0.17	0.23	-10000	0	-0.47	166	166
GSK3B	-0.14	0.2	-10000	0	-0.41	159	159
RAF1	-0.088	0.16	-10000	0	-0.33	91	91
SHC1	0.017	0.023	-10000	0	-0.52	1	1
STAT3	-0.17	0.22	-10000	0	-0.47	163	163
STAT1	-0.37	0.49	-10000	0	-0.92	205	205
HRAS/SPRED1	-0.095	0.17	-10000	0	-0.35	99	99
cell proliferation	-0.17	0.22	-10000	0	-0.45	165	165
PIK3CA	0.015	0.029	-10000	0	-0.34	3	3
TEC	0.013	0.052	-10000	0	-0.52	5	5
RPS6KB1	-0.17	0.22	-10000	0	-0.46	169	169
HRAS/SPRED2	-0.095	0.17	-10000	0	-0.35	96	96
LYN/TEC/p62DOK	-0.15	0.22	-10000	0	-0.45	163	163
MAPK3	-0.053	0.12	-10000	0	-0.26	54	54
STAP1	-0.19	0.24	-10000	0	-0.48	176	176
GRAP2	0.012	0.042	-10000	0	-0.28	10	10
JAK2	-0.31	0.4	-10000	0	-0.75	213	213
STAT1 (dimer)	-0.36	0.47	-10000	0	-0.89	205	205
mol:Gleevec	0.005	0.008	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.16	0.23	-10000	0	-0.45	168	168
actin filament polymerization	-0.17	0.22	-10000	0	-0.44	182	182
LYN	0.014	0.031	-10000	0	-0.25	7	7
STAP1/STAT5A (dimer)	-0.24	0.31	-10000	0	-0.64	166	166
PIK3R1	-0.01	0.11	-10000	0	-0.42	33	33
CBL/CRKL/GRB2	-0.13	0.2	-10000	0	-0.41	153	153
PI3K	-0.16	0.23	-10000	0	-0.45	169	169
PTEN	-0.001	0.1	-10000	0	-0.52	19	19
SCF/KIT/EPO/EPOR	-0.39	0.54	-10000	0	-1.2	152	152
MAPK8	-0.17	0.22	-10000	0	-0.46	165	165
STAT3 (dimer)	-0.17	0.22	-10000	0	-0.46	163	163
positive regulation of transcription	-0.042	0.1	-10000	0	-0.21	53	53
mol:GDP	-0.12	0.2	-10000	0	-0.4	148	148
PIK3C2B	-0.17	0.22	-10000	0	-0.47	164	164
CBL/CRKL	-0.14	0.21	-10000	0	-0.42	165	165
FER	-0.17	0.22	-10000	0	-0.47	163	163
SH2B3	-0.17	0.22	-10000	0	-0.46	163	163
PDPK1	-0.14	0.18	-10000	0	-0.39	150	150
SNAI2	-0.19	0.25	-10000	0	-0.5	177	177
positive regulation of cell proliferation	-0.27	0.36	-10000	0	-0.67	213	213
KITLG	-0.096	0.2	-10000	0	-0.45	123	123
cell motility	-0.27	0.36	-10000	0	-0.67	213	213
PTPN6	0.023	0.037	-10000	0	-0.43	3	3
EPOR	-0.091	0.16	-10000	0	-0.96	2	2
STAT5A (dimer)	-0.22	0.3	-10000	0	-0.59	187	187
SOCS1	0.015	0.031	-10000	0	-0.32	4	4
cell migration	0.17	0.22	0.46	170	-10000	0	170
SOS1	0.017	0.023	-10000	0	-0.52	1	1
EPO	-0.03	0.099	-10000	0	-0.26	80	80
VAV1	-0.014	0.12	-10000	0	-0.39	42	42
GRB10	-0.18	0.23	-10000	0	-0.47	168	168
PTPN11	0.022	0.024	-10000	0	-0.5	1	1
SCF/KIT	-0.18	0.23	-10000	0	-0.47	181	181
GO:0007205	0.008	0.011	-10000	0	-10000	0	0
MAP2K1	-0.063	0.13	-10000	0	-0.28	58	58
CBL	0.017	0.012	-10000	0	-0.25	1	1
KIT	-0.33	0.53	-10000	0	-1.2	131	131
MAP2K2	-0.064	0.13	-10000	0	-0.29	59	59
SHC/Grb2/SOS1	-0.14	0.22	-10000	0	-0.43	161	161
STAT5A	-0.23	0.31	-10000	0	-0.61	186	186
GRB2	0.016	0.024	-10000	0	-0.25	4	4
response to radiation	-0.19	0.24	-10000	0	-0.49	177	177
SHC/GRAP2	0.022	0.034	-10000	0	-0.37	2	2
PTPRO	-0.18	0.23	-10000	0	-0.48	166	166
SH2B2	-0.18	0.22	-10000	0	-0.44	182	182
DOK1	0.002	0.083	-10000	0	-0.41	19	19
MATK	-0.18	0.23	-10000	0	-0.47	170	170
CREBBP	0.003	0.059	-10000	0	-0.54	2	2
BCL2	-0.33	0.55	-10000	0	-1.3	120	120

×

FOXM1 transcription factor network

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
NFATC3	-0.24	0.57	-10000	0	-1.1	111	111
PLK1	0.024	0.058	-10000	0	-10000	0	0
BIRC5	-0.092	0.39	-10000	0	-1.4	40	40
HSPA1B	-0.25	0.56	-10000	0	-1.1	127	127
MAP2K1	0.018	0.047	-10000	0	-0.3	1	1
BRCA2	-0.26	0.59	-10000	0	-1.2	121	121
FOXM1	-0.4	0.94	-10000	0	-1.7	126	126
XRCC1	-0.24	0.57	-10000	0	-1.1	113	113
FOXM1B/p19	-0.42	0.55	0.45	1	-1.2	140	141
Cyclin D1/CDK4	-0.3	0.57	-10000	0	-1.1	156	156
CDC2	-0.27	0.62	-10000	0	-1.2	114	114
TGFA	-0.29	0.55	-10000	0	-1	147	147
SKP2	-0.24	0.57	-10000	0	-1.1	111	111
CCNE1	-0.019	0.1	-10000	0	-0.29	64	64
CKS1B	-0.24	0.57	-10000	0	-1.1	122	122
RB1	-0.22	0.32	-10000	0	-0.88	74	74
FOXM1C/SP1	-0.31	0.67	-10000	0	-1.3	130	130
AURKB	0.011	0.13	-10000	0	-1.4	3	3
CENPF	-0.26	0.6	-10000	0	-1.2	117	117
CDK4	0.013	0.032	-10000	0	-0.26	5	5
MYC	-0.22	0.52	-10000	0	-0.96	133	133
CHEK2	0.011	0.073	-10000	0	-0.41	9	9
ONECUT1	-0.28	0.57	-10000	0	-1.1	139	139
CDKN2A	-0.056	0.15	-10000	0	-0.33	108	108
LAMA4	-0.24	0.58	-10000	0	-1.1	112	112
FOXM1B/HNF6	-0.37	0.71	-10000	0	-1.4	144	144
FOS	-0.34	0.64	-10000	0	-1.2	158	158
SP1	0.017	0.024	-10000	0	-0.52	1	1
CDC25B	-0.24	0.57	-10000	0	-1.1	111	111
response to radiation	0	0.039	-10000	0	-10000	0	0
CENPB	-0.24	0.57	-10000	0	-1.1	106	106
CENPA	-0.27	0.61	-10000	0	-1.2	113	113
NEK2	-0.29	0.62	-10000	0	-1.2	135	135
HIST1H2BA	-0.24	0.57	-10000	0	-1.1	115	115
CCNA2	-0.027	0.14	-10000	0	-0.4	57	57
EP300	0.014	0.047	-10000	0	-0.52	4	4
CCNB1/CDK1	-0.32	0.7	-10000	0	-1.5	99	99
CCNB2	-0.25	0.59	-10000	0	-1.2	115	115
CCNB1	-0.27	0.62	-10000	0	-1.2	113	113
ETV5	-0.25	0.58	-10000	0	-1.1	114	114
ESR1	-0.43	0.71	-10000	0	-1.2	219	219
CCND1	-0.31	0.6	-10000	0	-1.1	157	157
GSK3A	0.019	0.037	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.014	0.13	-10000	0	-0.35	53	53
CDK2	0.011	0.048	-10000	0	-0.31	10	10
G2/M transition of mitotic cell cycle	0	0.046	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.38	0.53	-10000	0	-1.2	131	131
GAS1	-0.32	0.64	-10000	0	-1.2	149	149
MMP2	-0.28	0.62	-10000	0	-1.2	124	124
RB1/FOXM1C	-0.31	0.6	-10000	0	-1.1	154	154
CREBBP	0.016	0.033	-10000	0	-0.52	2	2

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.017	0.023	-9999	-0.52	1	1
CCL5	-0.051	0.18	-9999	-0.49	71	71
SDCBP	0.003	0.081	-9999	-0.4	19	19
FGFR/FGF2/Syndecan-1	-0.17	0.27	-9999	-0.46	180	180
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.16	0.26	-9999	-0.54	126	126
Syndecan-1/Syntenin	-0.16	0.26	-9999	-0.53	129	129
MAPK3	-0.13	0.24	-9999	-0.53	104	104
HGF/MET	0.007	0.073	-9999	-0.38	13	13
TGFB1/TGF beta receptor Type II	0.017	0.023	-9999	-0.52	1	1
BSG	0.016	0.024	-9999	-0.25	4	4
keratinocyte migration	-0.15	0.25	-9999	-0.53	126	126
Syndecan-1/RANTES	-0.18	0.28	-9999	-0.53	157	157
Syndecan-1/CD147	-0.14	0.26	-9999	-0.54	117	117
Syndecan-1/Syntenin/PIP2	-0.15	0.25	-9999	-0.52	129	129
LAMA5	0.005	0.075	-9999	-0.41	15	15
positive regulation of cell-cell adhesion	-0.15	0.24	-9999	-0.5	129	129
MMP7	-0.095	0.21	-9999	-0.44	129	129
HGF	0.008	0.069	-9999	-0.45	11	11
Syndecan-1/CASK	-0.16	0.26	-9999	-0.44	180	180
Syndecan-1/HGF/MET	-0.15	0.26	-9999	-0.55	116	116
regulation of cell adhesion	-0.12	0.23	-9999	-0.51	106	106
HPSE	-0.015	0.12	-9999	-0.39	43	43
positive regulation of cell migration	-0.17	0.27	-9999	-0.46	180	180
SDC1	-0.17	0.27	-9999	-0.46	180	180
Syndecan-1/Collagen	-0.17	0.27	-9999	-0.46	180	180
PPIB	0.014	0.044	-9999	-0.41	5	5
MET	0	0.075	-9999	-0.29	31	31
PRKACA	0.018	0	-9999	-10000	0	0
MMP9	-0.042	0.17	-9999	-0.51	60	60
MAPK1	-0.13	0.24	-9999	-0.53	106	106
homophilic cell adhesion	-0.16	0.26	-9999	-0.45	180	180
MMP1	-0.19	0.22	-9999	-0.38	269	269

×

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	0.015	0.026	-10000	0	-0.25	5	5
PTK2	0.016	0.029	-10000	0	-0.34	3	3
CRKL	-0.1	0.19	-10000	0	-0.37	154	154
GRB2/SOS1/SHC	0.034	0.025	-10000	0	-0.3	2	2
HRAS	0.012	0.051	-10000	0	-0.41	7	7
IRS1/Crk	-0.1	0.19	-10000	0	-0.36	154	154
IGF-1R heterotetramer/IGF1/PTP1B	-0.11	0.18	-10000	0	-0.37	155	155
AKT1	-0.086	0.18	-10000	0	-0.42	84	84
BAD	-0.075	0.17	-10000	0	-0.39	84	84
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.1	0.19	-10000	0	-0.36	154	154
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.1	0.19	-10000	0	-0.35	169	169
RAF1	-0.063	0.16	-10000	0	-0.39	70	70
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.088	0.19	-10000	0	-0.34	153	153
YWHAZ	0.017	0.017	-10000	0	-0.25	2	2
IGF-1R heterotetramer/IGF1/IRS1	-0.12	0.2	-10000	0	-0.38	169	169
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
RPS6KB1	-0.086	0.18	-10000	0	-0.4	95	95
GNB2L1	0.015	0.04	-10000	0	-0.52	3	3
positive regulation of MAPKKK cascade	-0.058	0.14	-10000	0	-0.34	70	70
PXN	0.018	0	-10000	0	-10000	0	0
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.024	0.023	-10000	0	-0.37	1	1
HRAS/GTP	-0.099	0.15	-10000	0	-0.43	73	73
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.06	0.15	-10000	0	-0.35	71	71
IGF-1R heterotetramer	-0.1	0.22	-10000	0	-0.51	110	110
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.1	0.19	-10000	0	-0.37	152	152
Crk/p130 Cas/Paxillin	-0.078	0.18	-10000	0	-0.32	154	154
IGF1R	-0.1	0.22	-10000	0	-0.51	110	110
IGF1	-0.12	0.22	-10000	0	-0.44	146	146
IRS2/Crk	-0.11	0.2	-10000	0	-0.36	166	166
PI3K	-0.1	0.2	-10000	0	-0.36	164	164
apoptosis	0.057	0.15	0.34	84	-10000	0	84
HRAS/GDP	0.009	0.036	-10000	0	-0.29	7	7
PRKCD	-0.096	0.21	-10000	0	-0.39	153	153
RAF1/14-3-3 E	-0.048	0.14	-10000	0	-0.34	69	69
BAD/14-3-3	-0.061	0.16	-10000	0	-0.36	84	84
PRKCZ	-0.09	0.18	-10000	0	-0.32	164	164
Crk/p130 Cas/Paxillin/FAK1	-0.087	0.14	-10000	0	-0.37	75	75
PTPN1	0.002	0.07	-10000	0	-0.28	28	28
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.11	0.22	-10000	0	-0.41	153	153
BCAR1	0.017	0.012	-10000	0	-0.25	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.086	0.17	-10000	0	-0.32	163	163
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.017	0.023	-10000	0	-0.52	1	1
IRS1/NCK2	-0.1	0.19	-10000	0	-0.37	152	152
GRB10	-0.003	0.097	-10000	0	-0.43	24	24
PTPN11	-0.1	0.19	-10000	0	-0.35	169	169
IRS1	-0.12	0.2	-10000	0	-0.38	169	169
IRS2	-0.12	0.21	-10000	0	-0.37	181	181
IGF-1R heterotetramer/IGF1	-0.14	0.22	-10000	0	-0.46	156	156
GRB2	0.016	0.024	-10000	0	-0.25	4	4
PDPK1	-0.094	0.18	-10000	0	-0.33	164	164
YWHAE	0.016	0.029	-10000	0	-0.34	3	3
PRKD1	-0.12	0.23	-10000	0	-0.42	155	155
SHC1	0.017	0.023	-10000	0	-0.52	1	1

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.13	0.21	-9999	-0.46	102	102
FZD6	-0.077	0.2	-9999	-0.45	108	108
WNT6	-0.011	0.087	-9999	-0.26	54	54
WNT4	-0.062	0.18	-9999	-0.45	90	90
FZD3	-0.03	0.15	-9999	-0.48	51	51
WNT5A	-0.084	0.2	-9999	-0.43	120	120
WNT11	-0.013	0.089	-9999	-0.26	57	57

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.017	0.037	-10000	0	-0.36	3	3
NFATC2	-0.11	0.26	-10000	0	-0.59	81	81
NFATC3	-0.055	0.11	-10000	0	-0.24	74	74
CD40LG	-0.32	0.43	-10000	0	-0.89	157	157
ITCH	0.006	0.085	-10000	0	-10000	0	0
CBLB	0.005	0.088	-10000	0	-0.59	1	1
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.23	0.38	-10000	0	-0.88	94	94
JUNB	0.011	0.055	-10000	0	-0.36	10	10
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.008	0.1	-10000	0	-0.27	48	48
T cell anergy	-0.033	0.14	-10000	0	-0.39	48	48
TLE4	-0.071	0.23	-10000	0	-0.72	37	37
Jun/NFAT1-c-4/p21SNFT	-0.3	0.45	-10000	0	-0.91	148	148
AP-1/NFAT1-c-4	-0.37	0.52	-10000	0	-1	158	158
IKZF1	-0.08	0.23	-10000	0	-0.69	43	43
T-helper 2 cell differentiation	-0.22	0.35	-10000	0	-0.76	124	124
AP-1/NFAT1	-0.14	0.24	-10000	0	-0.5	121	121
CALM1	0.003	0.058	-10000	0	-10000	0	0
EGR2	-0.29	0.52	-10000	0	-1.1	115	115
EGR3	-0.37	0.58	-10000	0	-1.2	142	142
NFAT1/FOXP3	-0.064	0.2	-10000	0	-0.52	49	49
EGR1	-0.1	0.2	-10000	0	-0.39	156	156
JUN	-0.035	0.15	-10000	0	-0.46	57	57
EGR4	0	0.007	-10000	0	-10000	0	0
mol:Ca2+	-0.016	0.06	-10000	0	-0.17	48	48
GBP3	-0.14	0.31	-10000	0	-0.74	95	95
FOSL1	0.016	0.024	-10000	0	-0.25	4	4
NFAT1-c-4/MAF/IRF4	-0.28	0.44	-10000	0	-0.85	161	161
DGKA	-0.066	0.21	-10000	0	-0.68	34	34
CREM	0.016	0.017	-10000	0	-0.26	2	2
NFAT1-c-4/PPARG	-0.3	0.46	-10000	0	-0.9	162	162
CTLA4	-0.052	0.18	-10000	0	-0.55	37	37
NFAT1-c-4 (dimer)/EGR1	-0.33	0.48	-10000	0	-0.94	166	166
NFAT1-c-4 (dimer)/EGR4	-0.28	0.44	-10000	0	-0.88	159	159
FOS	-0.11	0.2	-10000	0	-0.37	171	171
IFNG	-0.3	0.47	-10000	0	-1.1	94	94
T cell activation	-0.17	0.29	-10000	0	-0.75	64	64
MAF	-0.012	0.12	-10000	0	-0.44	35	35
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.22	0.38	0.73	152	-10000	0	152
TNF	-0.3	0.42	-10000	0	-0.83	169	169
FASLG	-0.43	0.65	-10000	0	-1.3	167	167
TBX21	-0.11	0.21	-10000	0	-0.46	137	137
BATF3	0	0.001	-10000	0	-10000	0	0
PRKCQ	-0.018	0.11	-10000	0	-0.32	51	51
PTPN1	-0.069	0.2	-10000	0	-0.58	44	44
NFAT1-c-4/ICER1	-0.28	0.44	-10000	0	-0.88	156	156
GATA3	-0.1	0.23	-10000	0	-0.51	124	124
T-helper 1 cell differentiation	-0.28	0.44	-10000	0	-1.1	97	97
IL2RA	-0.25	0.35	-10000	0	-0.81	108	108
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.058	0.19	-10000	0	-0.53	43	43
E2F1	0.013	0.071	-10000	0	-0.36	16	16
PPARG	-0.036	0.14	-10000	0	-0.33	81	81
SLC3A2	-0.06	0.19	-10000	0	-0.56	38	38
IRF4	-0.01	0.085	-10000	0	-0.26	52	52
PTGS2	-0.33	0.44	-10000	0	-0.89	161	161
CSF2	-0.33	0.43	-10000	0	-0.89	159	159
JunB/Fra1/NFAT1-c-4	-0.26	0.43	-10000	0	-0.84	156	156
IL4	-0.24	0.37	-10000	0	-0.8	123	123
IL5	-0.32	0.43	-10000	0	-0.88	158	158
IL2	-0.18	0.29	-10000	0	-0.78	61	61
IL3	-0.04	0.052	-10000	0	-10000	0	0
RNF128	-0.053	0.2	-10000	0	-0.6	47	47
NFATC1	-0.22	0.39	-10000	0	-0.73	152	152
CDK4	0.14	0.22	0.56	57	-10000	0	57
PTPRK	-0.12	0.3	-10000	0	-0.71	89	89
IL8	-0.36	0.44	-10000	0	-0.92	162	162
POU2F1	0.027	0	-10000	0	-10000	0	0

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.043	0.26	0.28	54	-0.58	61	115
PTK2B	0.017	0.017	-10000	0	-0.25	2	2
mol:Ca2+	-0.071	0.26	-10000	0	-0.68	54	54
EDN1	-0.065	0.24	0.23	20	-0.5	98	118
EDN3	-0.1	0.18	-10000	0	-0.32	190	190
EDN2	-0.13	0.22	-10000	0	-0.41	185	185
HRAS/GDP	-0.11	0.24	-10000	0	-0.47	119	119
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.087	0.22	-10000	0	-0.44	109	109
ADCY4	-0.043	0.21	-10000	0	-0.52	59	59
ADCY5	-0.06	0.22	-10000	0	-0.49	73	73
ADCY6	-0.041	0.21	-10000	0	-0.5	61	61
ADCY7	-0.046	0.22	-10000	0	-0.52	61	61
ADCY1	-0.04	0.21	-10000	0	-0.5	60	60
ADCY2	-0.075	0.24	-10000	0	-0.5	87	87
ADCY3	-0.044	0.21	-10000	0	-0.5	64	64
ADCY8	-0.043	0.21	-10000	0	-0.5	59	59
ADCY9	-0.05	0.22	-10000	0	-0.5	67	67
arachidonic acid secretion	-0.12	0.26	-10000	0	-0.5	134	134
ETB receptor/Endothelin-1/Gq/GTP	-0.079	0.18	-10000	0	-0.35	114	114
GNAO1	0.016	0.024	-10000	0	-0.25	4	4
HRAS	0.011	0.051	-10000	0	-0.41	7	7
ETA receptor/Endothelin-1/G12/GTP	-0.002	0.27	0.36	73	-0.56	57	130
ETA receptor/Endothelin-1/Gs/GTP	-0.007	0.26	0.34	72	-0.53	59	131
mol:GTP	-0.001	0.006	-10000	0	-10000	0	0
COL3A1	-0.048	0.28	-10000	0	-0.67	59	59
EDNRB	-0.03	0.13	-10000	0	-0.39	52	52
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.042	0.26	-10000	0	-0.62	58	58
CYSLTR1	-0.075	0.3	-10000	0	-0.65	83	83
SLC9A1	-0.01	0.15	0.2	56	-0.3	57	113
mol:GDP	-0.12	0.26	-10000	0	-0.5	126	126
SLC9A3	-0.13	0.34	-10000	0	-0.66	126	126
RAF1	-0.13	0.25	-10000	0	-0.49	130	130
JUN	-0.11	0.36	-10000	0	-0.98	62	62
JAK2	-0.043	0.26	0.28	56	-0.58	62	118
mol:IP3	-0.11	0.22	-10000	0	-0.44	121	121
ETA receptor/Endothelin-1	-0.019	0.32	0.42	77	-0.57	84	161
PLCB1	-0.086	0.18	-10000	0	-0.38	138	138
PLCB2	0.014	0.027	-10000	0	-0.39	2	2
ETA receptor/Endothelin-3	-0.074	0.19	-10000	0	-0.4	99	99
FOS	-0.18	0.35	-10000	0	-0.87	92	92
Gai/GDP	-0.007	0.14	-10000	0	-0.82	10	10
CRK	0.016	0.033	-10000	0	-0.52	2	2
mol:Ca ++	-0.14	0.32	-10000	0	-0.6	127	127
BCAR1	0.017	0.012	-10000	0	-0.25	1	1
PRKCB1	-0.13	0.24	-10000	0	-0.47	131	131
GNAQ	-0.001	0.007	-10000	0	-10000	0	0
GNAZ	0.001	0.088	-10000	0	-0.44	19	19
GNAL	0.011	0.052	-10000	0	-0.33	11	11
Gs family/GDP	-0.12	0.22	-10000	0	-0.46	116	116
ETA receptor/Endothelin-1/Gq/GTP	-0.068	0.23	-10000	0	-0.45	101	101
MAPK14	-0.084	0.17	-10000	0	-0.37	98	98
TRPC6	-0.077	0.28	-10000	0	-0.74	50	50
GNAI2	0.006	0.075	-10000	0	-0.48	12	12
GNAI3	0.018	0	-10000	0	-10000	0	0
GNAI1	-0.017	0.12	-10000	0	-0.38	46	46
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.096	0.18	-10000	0	-0.35	130	130
ETB receptor/Endothelin-2	-0.11	0.18	-10000	0	-0.4	135	135
ETB receptor/Endothelin-3	-0.09	0.16	-10000	0	-0.37	94	94
ETB receptor/Endothelin-1	-0.068	0.21	-10000	0	-0.39	120	120
MAPK3	-0.17	0.34	-10000	0	-0.75	108	108
MAPK1	-0.17	0.34	-10000	0	-0.76	106	106
Rac1/GDP	-0.1	0.24	-10000	0	-0.46	121	121
cAMP biosynthetic process	-0.047	0.22	0.27	1	-0.48	74	75
MAPK8	-0.089	0.29	-10000	0	-0.68	74	74
SRC	0.015	0.035	-10000	0	-0.43	3	3
ETB receptor/Endothelin-1/Gi/GTP	-0.037	0.15	-10000	0	-0.36	61	61
p130Cas/CRK/Src/PYK2	-0.1	0.25	-10000	0	-0.52	110	110
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.1	0.24	-10000	0	-0.48	114	114
COL1A2	-0.12	0.38	-10000	0	-0.81	99	99
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.095	0.22	-10000	0	-0.41	148	148
mol:DAG	-0.11	0.22	-10000	0	-0.44	121	121
MAP2K2	-0.15	0.28	-10000	0	-0.6	118	118
MAP2K1	-0.15	0.28	-10000	0	-0.58	124	124
EDNRA	-0.003	0.2	-10000	0	-0.57	48	48
positive regulation of muscle contraction	-0.031	0.22	-10000	0	-0.51	61	61
Gq family/GDP	-0.13	0.21	-10000	0	-0.49	102	102
HRAS/GTP	-0.12	0.23	-10000	0	-0.45	129	129
PRKCH	-0.099	0.22	-10000	0	-0.45	113	113
RAC1	0.018	0	-10000	0	-10000	0	0
PRKCA	-0.098	0.22	-10000	0	-0.44	109	109
PRKCB	-0.1	0.21	-10000	0	-0.42	125	125
PRKCE	-0.099	0.22	-10000	0	-0.44	115	115
PRKCD	-0.098	0.22	-10000	0	-0.45	110	110
PRKCG	-0.097	0.22	-10000	0	-0.45	106	106
regulation of vascular smooth muscle contraction	-0.21	0.41	-10000	0	-1.1	89	89
PRKCQ	-0.11	0.23	-10000	0	-0.46	116	116
PLA2G4A	-0.14	0.28	-10000	0	-0.54	134	134
GNA14	-0.081	0.18	-10000	0	-0.35	140	140
GNA15	0.001	0.077	-10000	0	-0.34	23	23
GNA12	0.018	0	-10000	0	-10000	0	0
GNA11	0.012	0.047	-10000	0	-0.52	4	4
Rac1/GTP	-0.002	0.27	0.36	73	-0.55	58	131
MMP1	-0.25	0.4	-10000	0	-0.89	132	132

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.012	0.051	-9999	-0.41	7	7
EGFR	-0.079	0.18	-9999	-0.35	139	139
EGF/EGFR	-0.17	0.21	-9999	-0.37	229	229
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.085	0.16	-9999	-0.29	169	169
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.03	0.15	-9999	-0.5	49	49
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.14	0.23	-9999	-0.42	193	193
EGF/EGFR dimer/SHC	-0.12	0.18	-9999	-0.35	174	174
mol:GDP	-0.086	0.15	-9999	-0.29	169	169
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.097	0.21	-9999	-0.43	135	135
GRB2/SOS1	0.024	0.023	-9999	-0.37	1	1
HRAS/GTP	-0.1	0.12	-9999	-0.34	60	60
SHC1	0.017	0.023	-9999	-0.52	1	1
HRAS/GDP	-0.081	0.14	-9999	-0.35	60	60
FRAP1	-0.078	0.14	-9999	-0.35	58	58
EGF/EGFR dimer	-0.15	0.2	-9999	-0.42	173	173
SOS1	0.017	0.023	-9999	-0.52	1	1
GRB2	0.016	0.024	-9999	-0.25	4	4
ETA receptor/Endothelin-1	-0.089	0.19	-9999	-0.41	120	120

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.15	0.47	-9999	-0.94	99	99
HDAC7	0.001	0.006	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.13	0.39	-9999	-0.78	87	87
SMAD4	0.01	0.067	-9999	-0.49	9	9
ID2	-0.16	0.48	-9999	-0.94	103	103
AP1	-0.1	0.19	-9999	-0.42	114	114
ABCG2	-0.16	0.48	-9999	-0.94	103	103
HIF1A	-0.055	0.19	-9999	-0.53	59	59
TFF3	-0.23	0.52	-9999	-0.95	139	139
GATA2	-0.013	0.096	-9999	-0.33	40	40
AKT1	-0.006	0.1	-9999	-0.45	8	8
response to hypoxia	-0.02	0.084	-9999	-0.17	16	16
MCL1	-0.16	0.47	-9999	-0.92	103	103
NDRG1	-0.17	0.49	-9999	-0.96	102	102
SERPINE1	-0.17	0.48	-9999	-0.94	105	105
FECH	-0.16	0.48	-9999	-0.94	105	105
FURIN	-0.16	0.48	-9999	-0.94	101	101
NCOA2	0.009	0.063	-9999	-0.4	11	11
EP300	0.009	0.12	-9999	-0.38	12	12
HMOX1	-0.17	0.49	-9999	-0.95	106	106
BHLHE40	-0.17	0.46	-9999	-0.92	105	105
BHLHE41	-0.17	0.46	-9999	-0.92	105	105
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.008	0.16	-9999	-0.37	49	49
ENG	0.007	0.15	-9999	-0.35	43	43
JUN	-0.037	0.15	-9999	-0.47	57	57
RORA	-0.17	0.49	-9999	-0.94	110	110
ABCB1	-0.1	0.25	-9999	-1.2	24	24
TFRC	-0.18	0.49	-9999	-0.95	109	109
CXCR4	-0.18	0.49	-9999	-0.95	109	109
TF	-0.16	0.48	-9999	-0.93	103	103
CITED2	-0.16	0.48	-9999	-0.95	100	100
HIF1A/ARNT	-0.2	0.54	-9999	-1.1	90	90
LDHA	-0.043	0.15	-9999	-1.2	8	8
ETS1	-0.16	0.48	-9999	-0.94	102	102
PGK1	-0.16	0.47	-9999	-0.93	101	101
NOS2	-0.17	0.46	-9999	-0.92	105	105
ITGB2	-0.17	0.49	-9999	-0.94	111	111
ALDOA	-0.16	0.48	-9999	-0.94	101	101
Cbp/p300/CITED2	-0.16	0.48	-9999	-0.99	91	91
FOS	-0.11	0.2	-9999	-0.38	171	171
HK2	-0.16	0.47	-9999	-0.94	99	99
SP1	0.022	0.031	-9999	-0.52	1	1
GCK	0.011	0.2	-9999	-0.93	7	7
HK1	-0.16	0.47	-9999	-0.93	99	99
NPM1	-0.16	0.47	-9999	-0.93	101	101
EGLN1	-0.16	0.48	-9999	-0.94	103	103
CREB1	0.025	0.024	-9999	-0.52	1	1
PGM1	-0.16	0.48	-9999	-0.94	103	103
SMAD3	0.005	0.079	-9999	-0.41	17	17
EDN1	-0.22	0.48	-9999	-1.2	98	98
IGFBP1	-0.16	0.47	-9999	-0.93	101	101
VEGFA	-0.086	0.36	-9999	-0.71	83	83
HIF1A/JAB1	-0.038	0.14	-9999	-0.38	62	62
CP	-0.25	0.51	-9999	-0.98	127	127
CXCL12	-0.18	0.51	-9999	-1	106	106
COPS5	0.01	0.056	-9999	-0.35	11	11
SMAD3/SMAD4	0.013	0.074	-9999	-0.36	18	18
BNIP3	-0.16	0.48	-9999	-0.92	108	108
EGLN3	-0.2	0.5	-9999	-0.99	109	109
CA9	-0.17	0.49	-9999	-0.96	103	103
TERT	-0.16	0.48	-9999	-0.94	99	99
ENO1	-0.16	0.48	-9999	-0.94	100	100
PFKL	-0.16	0.48	-9999	-0.94	101	101
NCOA1	0.011	0.057	-9999	-0.52	6	6
ADM	-0.2	0.51	-9999	-0.98	113	113
ARNT	0.003	0.076	-9999	-10000	0	0
HNF4A	0.02	0.035	-9999	-0.52	2	2
ADFP	-0.17	0.49	-9999	-0.94	111	111
SLC2A1	-0.085	0.36	-9999	-0.72	81	81
LEP	-0.18	0.48	-9999	-0.92	112	112
HIF1A/ARNT/Cbp/p300	-0.13	0.4	-9999	-0.8	86	86
EPO	-0.092	0.35	-9999	-0.76	57	57
CREBBP	0.01	0.12	-9999	-0.36	10	10
HIF1A/ARNT/Cbp/p300/HDAC7	-0.13	0.39	-9999	-0.8	83	83
PFKFB3	-0.16	0.48	-9999	-0.94	103	103
NT5E	-0.16	0.48	-9999	-0.96	98	98

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.007	0.074	-9999	-0.5	11	11
LAT2	-0.089	0.18	-9999	-0.34	142	142
AP1	-0.14	0.22	-9999	-0.47	132	132
mol:PIP3	-0.099	0.22	-9999	-0.4	151	151
IKBKB	-0.043	0.12	-9999	-0.25	94	94
AKT1	-0.068	0.16	-9999	-0.4	73	73
IKBKG	-0.041	0.12	-9999	-0.25	89	89
MS4A2	-0.15	0.23	-9999	-0.43	203	203
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.015	0.029	-9999	-0.34	3	3
MAP3K1	-0.086	0.19	-9999	-0.41	109	109
mol:Ca2+	-0.071	0.16	-9999	-0.3	151	151
LYN	0.012	0.032	-9999	-0.26	7	7
CBLB	-0.086	0.18	-9999	-0.34	139	139
SHC1	0.017	0.023	-9999	-0.52	1	1
RasGAP/p62DOK	-0.013	0.11	-9999	-0.3	58	58
positive regulation of cell migration	-0.013	0.089	-9999	-0.28	46	46
INPP5D	0	0	-9999	-10000	0	0
PLD2	-0.088	0.18	-9999	-0.38	100	100
PTPN13	-0.12	0.22	-9999	-0.55	78	78
PTPN11	0.012	0.027	-9999	-0.56	1	1
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.046	0.14	-9999	-0.32	73	73
SYK	-0.025	0.14	-9999	-0.49	43	43
GRB2	0.015	0.024	-9999	-0.26	4	4
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.2	-9999	-0.41	152	152
LAT	-0.092	0.18	-9999	-0.34	143	143
PAK2	-0.081	0.2	-9999	-0.43	96	96
NFATC2	-0.042	0.082	-9999	-0.62	5	5
HRAS	-0.096	0.21	-9999	-0.38	147	147
GAB2	0.009	0.048	-9999	-0.25	17	17
PLA2G1B	0.038	0.026	-9999	-10000	0	0
Fc epsilon R1	-0.12	0.2	-9999	-0.39	168	168
Antigen/IgE/Fc epsilon R1	-0.11	0.19	-9999	-0.35	168	168
mol:GDP	-0.11	0.22	-9999	-0.41	149	149
JUN	-0.034	0.15	-9999	-0.46	57	57
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	-0.01	0.11	-9999	-0.42	33	33
FOS	-0.11	0.2	-9999	-0.37	171	171
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.097	0.18	-9999	-0.36	144	144
CHUK	-0.046	0.12	-9999	-0.25	99	99
KLRG1	-0.084	0.17	-9999	-0.31	145	145
VAV1	-0.1	0.2	-9999	-0.36	149	149
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.086	0.18	-9999	-0.34	139	139
negative regulation of mast cell degranulation	-0.079	0.16	-9999	-0.28	147	147
BTK	-0.11	0.23	-9999	-0.42	147	147
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.13	0.25	-9999	-0.41	178	178
GAB2/PI3K/SHP2	-0.1	0.15	-9999	-0.43	74	74
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.097	0.2	-9999	-0.44	98	98
RAF1	0.029	0.026	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.12	0.21	-9999	-0.36	184	184
FCER1G	0.02	0.026	-9999	-0.26	4	4
FCER1A	-0.074	0.2	-9999	-0.51	91	91
Antigen/IgE/Fc epsilon R1/Fyn	-0.095	0.18	-9999	-0.33	170	170
MAPK3	0.037	0.026	-9999	-10000	0	0
MAPK1	0.037	0.026	-9999	-10000	0	0
NFKB1	0.017	0.023	-9999	-0.52	1	1
MAPK8	-0.02	0.11	-9999	-0.48	19	19
DUSP1	-0.038	0.15	-9999	-0.41	69	69
NF-kappa-B/RelA	-0.039	0.061	-9999	-0.18	41	41
actin cytoskeleton reorganization	-0.088	0.18	-9999	-0.48	65	65
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.091	0.2	-9999	-0.45	99	99
FER	-0.086	0.18	-9999	-0.34	140	140
RELA	0.018	0	-9999	-10000	0	0
ITK	-0.053	0.13	-9999	-0.41	51	51
SOS1	0.017	0.023	-9999	-0.52	1	1
PLCG1	-0.1	0.22	-9999	-0.4	149	149
cytokine secretion	-0.029	0.044	-9999	-0.16	4	4
SPHK1	-0.11	0.2	-9999	-0.35	167	167
PTK2	-0.092	0.19	-9999	-0.5	65	65
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.21	-9999	-0.42	149	149
EDG1	-0.013	0.089	-9999	-0.28	46	46
mol:DAG	-0.095	0.22	-9999	-0.47	101	101
MAP2K2	0.032	0.031	-9999	-10000	0	0
MAP2K1	0.033	0.024	-9999	-10000	0	0
MAP2K7	0.017	0.023	-9999	-0.52	1	1
KLRG1/SHP2	-0.073	0.15	-9999	-0.37	77	77
MAP2K4	-0.011	0.16	-9999	-0.91	16	16
Fc epsilon R1/FcgammaRIIB	-0.12	0.22	-9999	-0.38	184	184
mol:Choline	-0.087	0.17	-9999	-0.38	100	100
SHC/Grb2/SOS1	-0.066	0.17	-9999	-0.41	74	74
FYN	0.008	0.067	-9999	-0.41	12	12
DOK1	0.002	0.083	-9999	-0.41	19	19
PXN	-0.079	0.18	-9999	-0.46	65	65
HCLS1	-0.096	0.19	-9999	-0.36	145	145
PRKCB	-0.069	0.16	-9999	-0.3	149	149
FCGR2B	-0.031	0.15	-9999	-0.5	50	50
IGHE	-0.003	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.08	0.16	-9999	-0.29	145	145
LCP2	-0.004	0.098	-9999	-0.4	27	27
PLA2G4A	-0.11	0.21	-9999	-0.38	157	157
RASA1	0.004	0.078	-9999	-0.42	16	16
mol:Phosphatidic acid	-0.087	0.17	-9999	-0.38	100	100
IKK complex	-0.023	0.098	-9999	-0.2	76	76
WIPF1	0.005	0.076	-9999	-0.4	16	16

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.058	0.14	-10000	0	-0.26	154	154
ER alpha/Gai/GDP/Gbeta gamma	-0.089	0.19	-10000	0	-0.35	156	156
AKT1	-0.2	0.35	-10000	0	-0.74	152	152
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.2	0.35	-10000	0	-0.75	152	152
mol:Ca2+	-0.1	0.18	-10000	0	-0.44	88	88
IGF1R	-0.083	0.2	-10000	0	-0.47	110	110
E2/ER alpha (dimer)/Striatin	-0.09	0.15	-10000	0	-0.32	155	155
SHC1	0.017	0.023	-10000	0	-0.52	1	1
apoptosis	0.19	0.33	0.7	154	-10000	0	154
RhoA/GTP	-0.086	0.12	-10000	0	-0.41	27	27
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.12	0.18	-10000	0	-0.38	155	155
regulation of stress fiber formation	0.041	0.12	0.29	41	-10000	0	41
E2/ERA-ERB (dimer)	-0.086	0.15	-10000	0	-0.31	150	150
KRAS	0.009	0.065	-10000	0	-0.44	10	10
G13/GTP	-0.08	0.14	-10000	0	-0.29	151	151
pseudopodium formation	-0.041	0.12	-10000	0	-0.29	41	41
E2/ER alpha (dimer)/PELP1	-0.086	0.15	-10000	0	-0.31	150	150
GRB2	0.016	0.024	-10000	0	-0.25	4	4
GNG2	0.016	0.029	-10000	0	-0.34	3	3
GNAO1	0.016	0.024	-10000	0	-0.25	4	4
HRAS	0.012	0.051	-10000	0	-0.41	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.11	0.22	-10000	0	-0.44	153	153
E2/ER beta (dimer)	0.013	0.008	-10000	0	-0.17	1	1
mol:GDP	-0.12	0.17	-10000	0	-0.39	150	150
mol:NADP	-0.11	0.22	-10000	0	-0.44	153	153
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
mol:IP3	-0.11	0.19	-10000	0	-0.46	88	88
IGF-1R heterotetramer	-0.083	0.2	-10000	0	-0.47	110	110
PLCB1	-0.12	0.19	-10000	0	-0.42	113	113
PLCB2	-0.074	0.17	-10000	0	-0.53	53	53
IGF1	-0.1	0.2	-10000	0	-0.41	146	146
mol:L-citrulline	-0.11	0.22	-10000	0	-0.44	153	153
RHOA	0.005	0.08	-10000	0	-0.52	12	12
Gai/GDP	-0.008	0.12	-10000	0	-0.75	10	10
JNK cascade	0.013	0.008	-10000	0	-0.17	1	1
BCAR1	0.017	0.012	-10000	0	-0.25	1	1
ESR2	0.017	0.012	-10000	0	-0.25	1	1
GNAQ	0	0	-10000	0	-10000	0	0
ESR1	-0.16	0.24	-10000	0	-0.46	199	199
Gq family/GDP/Gbeta gamma	-0.024	0.12	-10000	0	-0.49	19	19
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.044	0.13	-10000	0	-0.63	2	2
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.12	0.18	-10000	0	-0.38	156	156
GNAZ	0.001	0.088	-10000	0	-0.44	19	19
E2/ER alpha (dimer)	-0.12	0.17	-10000	0	-0.33	199	199
STRN	0.011	0.056	-10000	0	-0.42	8	8
GNAL	0.011	0.052	-10000	0	-0.33	11	11
PELP1	0.018	0	-10000	0	-10000	0	0
MAPK11	0.021	0.007	-10000	0	-10000	0	0
GNAI2	0.006	0.075	-10000	0	-0.48	12	12
GNAI3	0.018	0	-10000	0	-10000	0	0
GNAI1	-0.017	0.12	-10000	0	-0.38	46	46
HBEGF	-0.093	0.19	-10000	0	-0.41	71	71
cAMP biosynthetic process	-0.081	0.11	-10000	0	-0.25	152	152
SRC	-0.079	0.18	-10000	0	-0.33	157	157
PI3K	0.005	0.082	-10000	0	-0.37	21	21
GNB1	0.013	0.052	-10000	0	-0.52	5	5
G13/GDP/Gbeta gamma	-0.1	0.15	-10000	0	-0.33	151	151
SOS1	0.017	0.023	-10000	0	-0.52	1	1
IGF-1R heterotetramer/IGF1	-0.16	0.21	-10000	0	-0.44	168	168
Gs family/GTP	-0.066	0.13	-10000	0	-0.26	152	152
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.019	0.064	-10000	0	-0.28	20	20
vasodilation	-0.1	0.22	-10000	0	-0.42	153	153
mol:DAG	-0.11	0.19	-10000	0	-0.46	88	88
Gs family/GDP/Gbeta gamma	-0.1	0.15	-10000	0	-0.32	152	152
MSN	-0.045	0.13	-10000	0	-0.32	41	41
Gq family/GTP	-0.084	0.18	-10000	0	-0.53	58	58
mol:PI-3-4-5-P3	-0.19	0.34	-10000	0	-0.72	152	152
NRAS	0.005	0.076	-10000	0	-0.4	16	16
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.1	0.22	0.42	153	-10000	0	153
GRB2/SOS1	0.024	0.023	-10000	0	-0.37	1	1
RhoA/GDP	-0.093	0.18	-10000	0	-0.37	151	151
NOS3	-0.11	0.23	-10000	0	-0.46	153	153
GNA11	0.014	0.047	-10000	0	-0.52	4	4
MAPKKK cascade	-0.12	0.26	-10000	0	-0.53	154	154
E2/ER alpha (dimer)/PELP1/Src	-0.13	0.18	-10000	0	-0.4	155	155
ruffle organization	-0.041	0.12	-10000	0	-0.29	41	41
ROCK2	-0.051	0.13	-10000	0	-0.37	29	29
GNA14	-0.079	0.18	-10000	0	-0.35	140	140
GNA15	0.002	0.076	-10000	0	-0.34	23	23
GNA13	0.011	0.055	-10000	0	-0.36	10	10
MMP9	-0.095	0.18	-10000	0	-0.4	63	63
MMP2	-0.09	0.2	-10000	0	-0.44	65	65

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.067	0.099	0.23	128	-10000	0	128
RFC1	0.067	0.099	0.23	128	-10000	0	128
PRKDC	0.064	0.1	0.23	126	-0.3	1	127
RIPK1	0.018	0.024	-10000	0	-0.52	1	1
CASP7	-0.013	0.12	0.24	2	-0.68	14	16
FASLG/FAS/FADD/FAF1	-0.012	0.13	0.22	49	-0.3	48	97
MAP2K4	-0.045	0.16	-10000	0	-0.41	47	47
mol:ceramide	-0.044	0.15	-10000	0	-0.38	59	59
GSN	0.056	0.11	0.24	123	-0.3	11	134
FASLG/FAS/FADD/FAF1/Caspase 8	-0.013	0.13	-10000	0	-0.36	41	41
FAS	-0.026	0.13	-10000	0	-0.42	51	51
BID	0.012	0.066	0.29	16	-0.32	8	24
MAP3K1	-0.016	0.13	0.26	2	-0.34	40	42
MAP3K7	0.015	0.021	-10000	0	-0.25	3	3
RB1	0.054	0.11	0.23	117	-0.29	9	126
CFLAR	0.01	0.065	-10000	0	-0.44	10	10
HGF/MET	-0.036	0.14	-10000	0	-0.33	90	90
ARHGDIB	0.044	0.12	0.23	113	-0.29	20	133
FADD	-0.003	0.068	-10000	0	-0.26	35	35
actin filament polymerization	-0.056	0.11	0.3	11	-0.23	123	134
NFKB1	-0.042	0.08	-10000	0	-0.85	1	1
MAPK8	-0.06	0.19	-10000	0	-0.47	71	71
DFFA	0.066	0.099	0.23	127	-10000	0	127
DNA fragmentation during apoptosis	0.066	0.098	0.23	127	-10000	0	127
FAS/FADD/MET	-0.014	0.1	-10000	0	-0.33	39	39
CFLAR/RIP1	0.02	0.05	-10000	0	-0.36	8	8
FAIM3	-0.001	0.099	-10000	0	-0.49	20	20
FAF1	0.013	0.025	-10000	0	-0.52	1	1
PARP1	0.064	0.1	0.23	128	-0.28	5	133
DFFB	0.066	0.099	0.23	127	-10000	0	127
CHUK	-0.025	0.091	-10000	0	-0.43	6	6
FASLG	-0.065	0.17	-10000	0	-0.38	106	106
FAS/FADD	-0.02	0.11	-10000	0	-0.36	37	37
HGF	0.008	0.069	-10000	0	-0.45	11	11
LMNA	0.06	0.095	0.22	112	-0.26	8	120
CASP6	0.063	0.1	0.23	126	-0.27	4	130
CASP10	0.012	0.029	-10000	0	-0.25	6	6
CASP3	0.072	0.12	0.28	128	-10000	0	128
PTPN13	-0.071	0.2	-10000	0	-0.49	93	93
CASP8	0.013	0.068	0.37	18	-10000	0	18
IL6	-0.16	0.4	-10000	0	-1.2	59	59
MET	0	0.075	-10000	0	-0.29	31	31
ICAD/CAD	0.066	0.089	0.22	115	-10000	0	115
FASLG/FAS/FADD/FAF1/Caspase 10	-0.045	0.15	-10000	0	-0.38	59	59
activation of caspase activity by cytochrome c	0.012	0.066	0.29	16	-0.32	8	24
PAK2	0.067	0.099	0.23	128	-10000	0	128
BCL2	-0.11	0.22	-10000	0	-0.47	144	144

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.11	0.3	-10000	0	-0.69	66	66
CRP	-0.11	0.3	-10000	0	-0.67	73	73
cell cycle arrest	-0.14	0.34	-10000	0	-0.73	96	96
TIMP1	-0.11	0.3	-10000	0	-0.73	67	67
IL6ST	-0.11	0.22	-10000	0	-0.46	143	143
Rac1/GDP	-0.1	0.22	0.28	2	-0.42	131	133
AP1	-0.05	0.16	-10000	0	-0.45	33	33
GAB2	0.011	0.048	-10000	0	-0.25	17	17
TNFSF11	-0.18	0.41	-10000	0	-0.96	91	91
HSP90B1	0.008	0.11	-10000	0	-0.8	6	6
GAB1	0.007	0.074	-10000	0	-0.42	14	14
MAPK14	-0.11	0.22	-10000	0	-0.49	84	84
AKT1	0.038	0.073	-10000	0	-0.47	3	3
FOXO1	0.036	0.086	-10000	0	-0.45	5	5
MAP2K6	-0.12	0.22	0.27	2	-0.4	149	151
mol:GTP	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.1	0.25	-10000	0	-0.48	119	119
MITF	-0.11	0.22	0.29	2	-0.41	140	142
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.018	0	-10000	0	-10000	0	0
A2M	-0.042	0.28	-10000	0	-1.4	22	22
CEBPB	0.013	0.073	-10000	0	-0.33	20	20
GRB2/SOS1/GAB family/SHP2	-0.017	0.1	-10000	0	-0.41	9	9
STAT3	-0.15	0.37	-10000	0	-0.78	96	96
STAT1	-0.042	0.17	-10000	0	-0.95	16	16
CEBPD	-0.16	0.38	-10000	0	-0.9	85	85
PIK3CA	0.017	0.029	-10000	0	-0.34	3	3
PI3K	0.008	0.083	-10000	0	-0.37	21	21
JUN	-0.034	0.15	-10000	0	-0.46	57	57
PIAS3/MITF	-0.095	0.21	-10000	0	-0.44	100	100
MAPK11	-0.11	0.22	-10000	0	-0.48	88	88
STAT3 (dimer)/FOXO1	-0.082	0.29	-10000	0	-0.6	82	82
GRB2/SOS1/GAB family	-0.11	0.18	-10000	0	-0.47	72	72
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.12	0.22	-10000	0	-0.39	168	168
GRB2	0.017	0.024	-10000	0	-0.25	4	4
JAK2	0.01	0.053	-10000	0	-0.32	12	12
LBP	-0.097	0.26	-10000	0	-0.61	51	51
PIK3R1	-0.008	0.11	-10000	0	-0.42	33	33
JAK1	0.013	0.059	-10000	0	-0.53	6	6
MYC	-0.14	0.37	-10000	0	-0.85	84	84
FGG	-0.11	0.3	-10000	0	-0.67	75	75
macrophage differentiation	-0.14	0.34	-10000	0	-0.73	96	96
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.13	0.2	-10000	0	-0.34	207	207
JUNB	-0.11	0.29	-10000	0	-0.68	64	64
FOS	-0.11	0.2	-10000	0	-0.37	171	171
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.12	0.22	0.31	2	-0.42	146	148
STAT1/PIAS1	-0.11	0.22	0.32	2	-0.42	128	130
GRB2/SOS1/GAB family/SHP2/PI3K	0.03	0.067	-10000	0	-0.38	4	4
STAT3 (dimer)	-0.14	0.36	-10000	0	-0.77	96	96
PRKCD	-0.1	0.27	-10000	0	-0.57	91	91
IL6R	0.002	0.085	-10000	0	-0.37	23	23
SOCS3	-0.1	0.23	-10000	0	-0.67	42	42
gp130 (dimer)/JAK1/JAK1/LMO4	-0.096	0.19	-10000	0	-0.35	170	170
Rac1/GTP	-0.11	0.24	-10000	0	-0.45	120	120
HCK	-0.005	0.11	-10000	0	-0.47	25	25
MAPKKK cascade	0.008	0.093	-10000	0	-0.55	4	4
bone resorption	-0.16	0.38	-10000	0	-0.87	94	94
IRF1	-0.12	0.33	-10000	0	-0.79	68	68
mol:GDP	-0.12	0.23	0.29	2	-0.41	150	152
SOS1	0.018	0.024	-10000	0	-0.52	1	1
VAV1	-0.12	0.23	0.29	2	-0.42	150	152
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.11	0.22	-10000	0	-0.48	90	90
PTPN11	0.004	0.058	-10000	0	-1.2	1	1
IL6/IL6RA	-0.056	0.14	-10000	0	-0.36	79	79
gp130 (dimer)/TYK2/TYK2/LMO4	-0.095	0.18	-10000	0	-0.34	169	169
gp130 (dimer)/JAK2/JAK2/LMO4	-0.099	0.18	-10000	0	-0.35	174	174
IL6	-0.084	0.18	-10000	0	-0.36	146	146
PIAS3	0.018	0	-10000	0	-10000	0	0
PTPRE	-0.002	0.088	-10000	0	-0.47	17	17
PIAS1	0.017	0.012	-10000	0	-0.25	1	1
RAC1	0.018	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.11	0.18	0.27	2	-0.32	195	197
LMO4	-0.073	0.18	-10000	0	-0.38	123	123
STAT3 (dimer)/PIAS3	-0.14	0.34	-10000	0	-0.72	97	97
MCL1	0.043	0.083	-10000	0	-0.82	2	2

×

TCGA08_retinoblastoma

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
CDKN2B	-0.017	0.12	-10000	0	-0.38	46	46
CDKN2C	0.005	0.085	-10000	0	-0.37	23	23
CDKN2A	-0.052	0.15	-10000	0	-0.32	107	107
CCND2	0.019	0.085	0.2	74	-0.15	6	80
RB1	-0.022	0.092	0.15	3	-0.22	77	80
CDK4	0.026	0.096	0.23	77	-10000	0	77
CDK6	0.019	0.093	0.23	63	-0.2	6	69
G1/S progression	0.022	0.092	0.22	77	-0.15	3	80

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.33	0.63	-10000	0	-1.3	118	118
STAT6 (cleaved dimer)	-0.43	0.56	-10000	0	-1.2	144	144
IGHG1	-0.083	0.25	-10000	0	-0.48	45	45
IGHG3	-0.33	0.6	-10000	0	-1.2	139	139
AKT1	-0.11	0.31	-10000	0	-0.67	51	51
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.065	0.24	-10000	0	-0.61	27	27
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.14	0.34	-10000	0	-0.72	68	68
THY1	-0.35	0.65	-10000	0	-1.3	121	121
MYB	-0.097	0.22	-10000	0	-0.49	119	119
HMGA1	0.014	0.039	-10000	0	-0.36	5	5
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.14	0.34	-10000	0	-0.64	94	94
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.12	0.31	-10000	0	-0.66	53	53
SP1	0.021	0.03	-10000	0	-0.53	1	1
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.016	0.055	-10000	0	-0.4	7	7
STAT6 (dimer)/ETS1	-0.34	0.63	-10000	0	-1.2	138	138
SOCS1	-0.18	0.4	-10000	0	-0.78	105	105
SOCS3	-0.12	0.33	-10000	0	-0.91	27	27
FCER2	-0.22	0.46	-10000	0	-0.91	103	103
PARP14	0.006	0.078	-10000	0	-0.43	15	15
CCL17	-0.42	0.71	-10000	0	-1.4	148	148
GRB2	0.016	0.024	-10000	0	-0.25	4	4
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.083	0.26	-10000	0	-0.63	27	27
T cell proliferation	-0.35	0.65	-10000	0	-1.3	127	127
IL4R/JAK1	-0.35	0.64	-10000	0	-1.3	124	124
EGR2	-0.39	0.69	-10000	0	-1.4	136	136
JAK2	0.001	0.072	-10000	0	-0.34	12	12
JAK3	0.021	0.008	-10000	0	-10000	0	0
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
JAK1	0.012	0.061	-10000	0	-0.52	6	6
COL1A2	-0.22	0.54	-10000	0	-1.5	72	72
CCL26	-0.34	0.63	-10000	0	-1.3	118	118
IL4R	-0.37	0.7	-10000	0	-1.4	121	121
PTPN6	0.021	0.038	-10000	0	-0.42	3	3
IL13RA2	-0.38	0.67	-10000	0	-1.3	141	141
IL13RA1	-0.002	0.089	-10000	0	-0.49	12	12
IRF4	-0.038	0.2	-10000	0	-0.76	11	11
ARG1	-0.064	0.27	-10000	0	-0.87	28	28
CBL	-0.13	0.32	-10000	0	-0.61	91	91
GTF3A	0.02	0.032	-10000	0	-0.38	2	2
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
IL13RA1/JAK2	0.003	0.099	-10000	0	-0.36	18	18
IRF4/BCL6	-0.044	0.19	-10000	0	-0.71	11	11
CD40LG	0.012	0.07	-10000	0	-0.32	20	20
MAPK14	-0.13	0.33	-10000	0	-0.64	80	80
mitosis	-0.1	0.3	-10000	0	-0.64	50	50
STAT6	-0.43	0.85	-10000	0	-1.6	139	139
SPI1	0.012	0.07	-10000	0	-0.41	12	12
RPS6KB1	-0.099	0.29	-10000	0	-0.63	44	44
STAT6 (dimer)	-0.44	0.86	-10000	0	-1.6	139	139
STAT6 (dimer)/PARP14	-0.39	0.7	-10000	0	-1.4	140	140
mast cell activation	0.004	0.019	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.11	0.3	-10000	0	-0.67	49	49
FRAP1	-0.11	0.31	-10000	0	-0.67	51	51
LTA	-0.33	0.63	-10000	0	-1.3	118	118
FES	0.01	0.058	-10000	0	-0.39	10	10
T-helper 1 cell differentiation	0.39	0.75	1.4	139	-10000	0	139
CCL11	-0.38	0.65	-10000	0	-1.3	141	141
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.1	0.3	-10000	0	-0.69	32	32
IL2RG	0.001	0.08	-10000	0	-0.29	35	35
IL10	-0.34	0.63	-10000	0	-1.3	123	123
IRS1	-0.048	0.17	-10000	0	-0.49	68	68
IRS2	-0.026	0.13	-10000	0	-0.39	57	57
IL4	-0.039	0.22	-10000	0	-1.4	6	6
IL5	-0.34	0.63	-10000	0	-1.3	119	119
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.24	0.5	-10000	0	-0.94	131	131
COL1A1	-0.23	0.56	-10000	0	-1.6	72	72
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.37	0.67	-10000	0	-1.4	120	120
IL2R gamma/JAK3	0.017	0.059	-10000	0	-0.33	5	5
TFF3	-0.52	0.77	-10000	0	-1.4	193	193
ALOX15	-0.35	0.64	-10000	0	-1.3	126	126
MYBL1	-0.066	0.17	-10000	0	-0.36	117	117
T-helper 2 cell differentiation	-0.25	0.49	-10000	0	-0.95	130	130
SHC1	0.017	0.023	-10000	0	-0.52	1	1
CEBPB	0.008	0.075	-10000	0	-0.34	20	20
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.12	0.32	-10000	0	-0.73	44	44
mol:PI-3-4-5-P3	-0.11	0.31	-10000	0	-0.67	51	51
PI3K	-0.12	0.33	-10000	0	-0.71	52	52
DOK2	-0.021	0.13	-10000	0	-0.4	48	48
ETS1	0.007	0.07	-10000	0	-0.28	24	24
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.073	0.25	-10000	0	-0.62	23	23
ITGB3	-0.34	0.63	-10000	0	-1.3	117	117
PIGR	-0.5	0.76	-10000	0	-1.4	181	181
IGHE	0.022	0.086	0.2	52	-0.25	4	56
MAPKKK cascade	-0.071	0.24	-10000	0	-0.6	23	23
BCL6	-0.004	0.1	-10000	0	-0.46	24	24
OPRM1	-0.34	0.63	-10000	0	-1.4	100	100
RETNLB	-0.33	0.63	-10000	0	-1.3	116	116
SELP	-0.46	0.75	-10000	0	-1.5	158	158
AICDA	-0.35	0.61	-10000	0	-1.3	129	129

×

IL27-mediated signaling events

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
TGFB1	0.026	0.03	-10000	0	-0.46	2	2
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.17	0.26	0.61	102	-10000	0	102
IL27/IL27R/JAK1	-0.2	0.35	-10000	0	-0.86	84	84
TBX21	-0.22	0.3	-10000	0	-0.61	153	153
IL12B	0.001	0.075	-10000	0	-0.35	21	21
IL12A	-0.01	0.064	-10000	0	-0.19	55	55
IL6ST	-0.12	0.22	-10000	0	-0.47	143	143
IL27RA/JAK1	-0.11	0.33	-10000	0	-1.2	39	39
IL27	-0.082	0.2	-10000	0	-0.5	98	98
TYK2	0.011	0.011	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.006	0.11	-10000	0	-1.4	1	1
T-helper 2 cell differentiation	0.17	0.26	0.61	102	-10000	0	102
T cell proliferation during immune response	0.17	0.26	0.61	102	-10000	0	102
MAPKKK cascade	-0.17	0.26	-10000	0	-0.61	102	102
STAT3	0.015	0.04	-10000	0	-0.52	3	3
STAT2	0.018	0	-10000	0	-10000	0	0
STAT1	-0.021	0.12	-10000	0	-0.33	58	58
IL12RB1	0.017	0.003	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.21	0.28	-10000	0	-0.58	158	158
IL27/IL27R/JAK2/TYK2	-0.17	0.27	-10000	0	-0.62	102	102
positive regulation of T cell mediated cytotoxicity	-0.17	0.26	-10000	0	-0.61	102	102
STAT1 (dimer)	-0.27	0.4	0.46	9	-0.91	104	113
JAK2	0.004	0.055	-10000	0	-0.33	12	12
JAK1	0.011	0.057	-10000	0	-0.52	6	6
STAT2 (dimer)	-0.16	0.25	-10000	0	-0.58	102	102
T cell proliferation	-0.2	0.27	-10000	0	-0.6	125	125
IL12/IL12R/TYK2/JAK2	-0.033	0.15	-10000	0	-0.85	9	9
IL17A	-0.006	0.11	-10000	0	-1.4	1	1
mast cell activation	0.17	0.26	0.61	102	-10000	0	102
IFNG	-0.031	0.047	-10000	0	-0.11	94	94
T cell differentiation	-0.01	0.009	0.017	2	-0.021	176	178
STAT3 (dimer)	-0.16	0.25	-10000	0	-0.58	103	103
STAT5A (dimer)	-0.16	0.26	-10000	0	-0.59	104	104
STAT4 (dimer)	-0.17	0.27	-10000	0	-0.59	120	120
STAT4	-0.024	0.13	-10000	0	-0.42	50	50
T cell activation	0.002	0.038	0.08	81	-10000	0	81
IL27R/JAK2/TYK2	-0.16	0.33	-10000	0	-0.93	63	63
GATA3	-0.25	0.55	-10000	0	-1.3	119	119
IL18	-0.035	0.12	-10000	0	-0.32	76	76
positive regulation of mast cell cytokine production	-0.15	0.25	-10000	0	-0.57	103	103
IL27/EBI3	-0.06	0.16	-10000	0	-0.38	93	93
IL27RA	-0.12	0.34	-10000	0	-1.3	38	38
IL6	-0.077	0.18	-10000	0	-0.35	147	147
STAT5A	0.011	0.056	-10000	0	-0.42	8	8
monocyte differentiation	-0.001	0.002	-10000	0	-10000	0	0
IL2	0.054	0.16	0.49	38	-1.2	3	41
IL1B	-0.033	0.12	-10000	0	-0.29	81	81
EBI3	0.002	0.071	-10000	0	-0.44	12	12
TNF	-0.003	0.067	-10000	0	-0.25	31	31

×

Glucocorticoid receptor regulatory network

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
PCK2	0.018	0.15	0.35	14	-0.84	10	24
SMARCC2	0.018	0	-10000	0	-10000	0	0
SMARCC1	0.012	0.051	-10000	0	-0.41	7	7
TBX21	-0.2	0.33	-10000	0	-0.74	124	124
SUMO2	0.014	0.022	-10000	0	-0.26	3	3
STAT1 (dimer)	-0.023	0.13	-10000	0	-0.34	67	67
FKBP4	0.012	0.055	-10000	0	-0.44	7	7
FKBP5	-0.045	0.16	-10000	0	-0.42	75	75
GR alpha/HSP90/FKBP51/HSP90	0.073	0.16	0.29	76	-0.31	28	104
PRL	-0.057	0.14	-10000	0	-0.87	3	3
cortisol/GR alpha (dimer)/TIF2	0.23	0.26	0.53	182	-0.4	2	184
RELA	-0.052	0.091	-10000	0	-0.26	21	21
FGG	0.2	0.22	0.48	141	-0.38	3	144
GR beta/TIF2	0.11	0.14	0.3	109	-0.32	14	123
IFNG	-0.41	0.43	-10000	0	-0.91	168	168
apoptosis	-0.004	0.18	0.5	6	-0.55	5	11
CREB1	0.007	0.056	-10000	0	-0.36	5	5
histone acetylation	-0.045	0.14	0.3	2	-0.35	51	53
BGLAP	-0.072	0.15	-10000	0	-0.49	23	23
GR/PKAc	0.092	0.14	0.29	65	-0.33	14	79
NF kappa B1 p50/RelA	-0.091	0.17	-10000	0	-0.4	63	63
SMARCD1	0.018	0	-10000	0	-10000	0	0
MDM2	0.099	0.1	0.24	137	-10000	0	137
GATA3	-0.093	0.23	-10000	0	-0.5	124	124
AKT1	0.006	0.059	0.21	4	-0.38	9	13
CSF2	-0.073	0.15	-10000	0	-0.87	7	7
GSK3B	0.016	0.008	-10000	0	-10000	0	0
NR1I3	0.009	0.18	0.52	2	-0.91	3	5
CSN2	0.17	0.18	0.42	110	-0.46	2	112
BRG1/BAF155/BAF170/BAF60A	0.041	0.034	-10000	0	-0.27	5	5
NFATC1	-0.004	0.12	-10000	0	-0.41	39	39
POU2F1	0.025	0.012	-10000	0	-0.22	1	1
CDKN1A	-0.035	0.28	-10000	0	-1.5	16	16
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.002	0.007	-10000	0	-10000	0	0
SFN	-0.015	0.12	-10000	0	-0.45	37	37
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.064	0.16	0.3	60	-0.32	30	90
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.086	0.33	0.5	2	-0.8	80	82
JUN	-0.21	0.24	-10000	0	-0.51	161	161
IL4	-0.1	0.2	-10000	0	-0.61	38	38
CDK5R1	0.013	0.031	-10000	0	-0.25	7	7
PRKACA	0.018	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.22	0.28	0.21	47	-0.49	227	274
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.081	0.15	0.3	63	-0.3	19	82
cortisol/GR alpha (monomer)	0.28	0.32	0.63	183	-0.46	3	186
NCOA2	0.009	0.063	-10000	0	-0.4	11	11
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.18	0.21	-10000	0	-0.45	171	171
AP-1/NFAT1-c-4	-0.44	0.4	-10000	0	-0.79	249	249
AFP	-0.16	0.2	-10000	0	-0.61	39	39
SUV420H1	0.014	0.037	-10000	0	-0.29	7	7
IRF1	0.11	0.25	0.46	44	-0.81	19	63
TP53	-0.015	0.17	-10000	0	-0.53	47	47
PPP5C	0.012	0.052	-10000	0	-0.39	8	8
KRT17	-0.53	0.58	-10000	0	-1.1	215	215
KRT14	-0.32	0.51	-10000	0	-1.4	94	94
TBP	0.028	0.012	-10000	0	-0.24	1	1
CREBBP	0.061	0.1	0.26	65	-0.53	2	67
HDAC1	0.011	0.025	-10000	0	-0.53	1	1
HDAC2	0.008	0.053	-10000	0	-0.29	15	15
AP-1	-0.44	0.4	-10000	0	-0.79	252	252
MAPK14	0.015	0.013	-10000	0	-0.25	1	1
MAPK10	-0.026	0.12	-10000	0	-0.36	58	58
MAPK11	0.016	0.008	-10000	0	-10000	0	0
KRT5	-0.54	0.58	-10000	0	-1.2	209	209
interleukin-1 receptor activity	-0.001	0.009	-10000	0	-10000	0	0
NCOA1	0.013	0.059	-10000	0	-0.52	6	6
STAT1	-0.023	0.13	-10000	0	-0.34	67	67
CGA	-0.12	0.2	-10000	0	-0.6	38	38
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.12	0.16	0.38	98	-0.39	2	100
MAPK3	0.014	0.027	-10000	0	-0.39	2	2
MAPK1	0.014	0.034	-10000	0	-0.52	2	2
ICAM1	-0.22	0.34	-10000	0	-0.84	84	84
NFKB1	-0.053	0.093	-10000	0	-0.3	14	14
MAPK8	-0.15	0.19	-10000	0	-0.42	128	128
MAPK9	-0.008	0.11	-10000	0	-0.51	24	24
cortisol/GR alpha (dimer)	-0.014	0.18	0.5	6	-0.58	5	11
BAX	0.001	0.11	-10000	0	-10000	0	0
POMC	-0.13	0.2	-10000	0	-1.3	5	5
EP300	0.059	0.11	0.26	65	-0.53	4	69
cortisol/GR alpha (dimer)/p53	0.21	0.28	0.54	166	-0.48	4	170
proteasomal ubiquitin-dependent protein catabolic process	0.07	0.08	0.21	78	-10000	0	78
SGK1	0.11	0.13	0.34	96	-0.26	4	100
IL13	-0.31	0.29	-10000	0	-0.71	128	128
IL6	-0.28	0.41	-10000	0	-0.9	123	123
PRKACG	0.016	0.033	-10000	0	-0.52	2	2
IL5	-0.26	0.24	-10000	0	-0.63	97	97
IL2	-0.32	0.33	-10000	0	-0.74	144	144
CDK5	0.015	0.027	-10000	0	-0.39	2	2
PRKACB	-0.036	0.14	-10000	0	-0.34	79	79
HSP90AA1	0.013	0.045	-10000	0	-0.39	6	6
IL8	-0.27	0.37	-10000	0	-0.82	122	122
CDK5R1/CDK5	0.02	0.03	-10000	0	-0.37	1	1
NF kappa B1 p50/RelA/PKAc	-0.063	0.15	-10000	0	-0.38	47	47
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.23	0.24	0.52	170	-10000	0	170
SMARCA4	0.015	0.031	-10000	0	-0.32	4	4
chromatin remodeling	0.16	0.16	0.36	141	-0.33	1	142
NF kappa B1 p50/RelA/Cbp	-0.018	0.16	0.34	6	-0.41	22	28
JUN (dimer)	-0.21	0.24	-10000	0	-0.5	161	161
YWHAH	0.013	0.048	-10000	0	-0.47	5	5
VIPR1	-0.11	0.24	-10000	0	-0.69	53	53
NR3C1	0.16	0.21	0.43	137	-0.46	11	148
NR4A1	0.01	0.063	-10000	0	-0.44	4	4
TIF2/SUV420H1	0.017	0.055	-10000	0	-0.42	6	6
MAPKKK cascade	-0.004	0.18	0.5	6	-0.55	5	11
cortisol/GR alpha (dimer)/Src-1	0.24	0.26	0.54	180	-0.43	3	183
PBX1	0.004	0.1	-10000	0	-0.48	23	23
POU1F1	0.023	0.033	-10000	0	-0.3	5	5
SELE	-0.35	0.47	-10000	0	-0.94	174	174
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.16	0.16	0.36	140	-0.34	1	141
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.23	0.24	0.52	170	-10000	0	170
mol:cortisol	0.16	0.19	0.37	183	-10000	0	183
MMP1	-0.44	0.52	-10000	0	-1.3	132	132

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.058	0.21	-10000	0	-0.45	97	97
FYN	-0.085	0.26	-10000	0	-0.55	105	105
LAT/GRAP2/SLP76	-0.098	0.21	-10000	0	-0.47	110	110
IKBKB	0.012	0.047	-10000	0	-0.31	10	10
AKT1	-0.048	0.19	-10000	0	-0.37	112	112
B2M	-0.005	0.1	-10000	0	-0.45	25	25
IKBKG	0.003	0.061	-10000	0	-0.13	48	48
MAP3K8	-0.036	0.15	-10000	0	-0.39	70	70
mol:Ca2+	-0.022	0.031	-10000	0	-0.083	66	66
integrin-mediated signaling pathway	0.007	0.068	-10000	0	-0.31	20	20
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.083	0.26	-10000	0	-0.54	111	111
TRPV6	-0.11	0.19	-10000	0	-0.38	159	159
CD28	-0.044	0.16	-10000	0	-0.4	78	78
SHC1	-0.09	0.26	-10000	0	-0.56	103	103
receptor internalization	-0.12	0.3	-10000	0	-0.59	123	123
PRF1	-0.079	0.24	-10000	0	-0.7	45	45
KRAS	0.009	0.065	-10000	0	-0.44	10	10
GRB2	0.016	0.024	-10000	0	-0.25	4	4
COT/AKT1	-0.047	0.16	-10000	0	-0.32	107	107
LAT	-0.095	0.27	-10000	0	-0.56	112	112
EntrezGene:6955	0	0.004	-10000	0	-10000	0	0
CD3D	-0.029	0.13	-10000	0	-0.35	68	68
CD3E	0.016	0.018	-10000	0	-0.26	2	2
CD3G	-0.092	0.2	-10000	0	-0.41	136	136
RASGRP2	-0.002	0.036	-10000	0	-0.11	27	27
RASGRP1	-0.061	0.2	-10000	0	-0.37	127	127
HLA-A	-0.012	0.12	-10000	0	-0.43	34	34
RASSF5	-0.004	0.096	-10000	0	-0.38	29	29
RAP1A/GTP/RAPL	0.007	0.068	-10000	0	-0.31	20	20
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.004	0.064	-10000	0	-0.11	71	71
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.045	0.078	-10000	0	-0.2	87	87
PRKCA	-0.043	0.1	-10000	0	-0.24	100	100
GRAP2	0.012	0.042	-10000	0	-0.28	10	10
mol:IP3	-0.051	0.18	0.18	83	-0.37	104	187
EntrezGene:6957	-0.001	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.08	0.22	-10000	0	-0.46	99	99
ORAI1	0.07	0.11	0.3	66	-0.38	1	67
CSK	-0.088	0.26	-10000	0	-0.55	103	103
B7 family/CD28	-0.11	0.3	-10000	0	-0.61	114	114
CHUK	0.005	0.081	-10000	0	-0.5	13	13
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.11	0.3	-10000	0	-0.64	104	104
PTPN6	-0.094	0.26	-10000	0	-0.57	102	102
VAV1	-0.1	0.28	-10000	0	-0.59	107	107
Monovalent TCR/CD3	-0.096	0.22	-10000	0	-0.41	142	142
CBL	0.017	0.012	-10000	0	-0.25	1	1
LCK	-0.097	0.28	-10000	0	-0.58	107	107
PAG1	-0.092	0.26	-10000	0	-0.56	104	104
RAP1A	0.012	0.057	-10000	0	-0.52	6	6
TCR/CD3/MHC I/CD8/LCK	-0.12	0.3	-10000	0	-0.64	106	106
CD80	0.009	0.048	-10000	0	-0.27	14	14
CD86	-0.008	0.11	-10000	0	-0.5	26	26
PDK1/CARD11/BCL10/MALT1	-0.054	0.094	-10000	0	-0.24	92	92
HRAS	0.012	0.051	-10000	0	-0.41	7	7
GO:0035030	-0.091	0.24	-10000	0	-0.5	115	115
CD8A	0	0.005	-10000	0	-10000	0	0
CD8B	0.001	0.069	-10000	0	-0.28	29	29
PTPRC	-0.041	0.16	-10000	0	-0.42	71	71
PDK1/PKC theta	-0.06	0.23	-10000	0	-0.46	108	108
CSK/PAG1	-0.08	0.25	-10000	0	-0.54	99	99
SOS1	0.017	0.023	-10000	0	-0.52	1	1
peptide-MHC class I	-0.01	0.13	-10000	0	-0.44	36	36
GRAP2/SLP76	-0.085	0.26	-10000	0	-0.55	106	106
STIM1	0.034	0.059	-10000	0	-0.53	1	1
RAS family/GTP	-0.002	0.088	-10000	0	-0.17	70	70
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.13	0.33	-10000	0	-0.64	122	122
mol:DAG	-0.072	0.14	0.13	1	-0.33	109	110
RAP1A/GDP	0.003	0.031	-10000	0	-0.077	21	21
PLCG1	0.016	0.026	-10000	0	-0.39	2	2
CD247	-0.11	0.21	-10000	0	-0.41	153	153
cytotoxic T cell degranulation	-0.076	0.23	-10000	0	-0.66	45	45
RAP1A/GTP	-0.005	0.014	-10000	0	-0.075	17	17
mol:PI-3-4-5-P3	-0.063	0.22	-10000	0	-0.44	111	111
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.076	0.23	0.21	77	-0.48	106	183
NRAS	0.005	0.076	-10000	0	-0.4	16	16
ZAP70	0.005	0.06	-10000	0	-0.27	24	24
GRB2/SOS1	0.024	0.023	-10000	0	-0.37	1	1
LAT/GRAP2/SLP76/VAV1	-0.1	0.21	0.16	1	-0.48	109	110
MALT1	0.011	0.053	-10000	0	-0.37	9	9
TRAF6	0.017	0.023	-10000	0	-0.52	1	1
CD8 heterodimer	0.002	0.049	-10000	0	-0.19	29	29
CARD11	0.002	0.077	-10000	0	-0.33	24	24
PRKCB	-0.048	0.1	-10000	0	-0.23	109	109
PRKCE	-0.045	0.11	-10000	0	-0.24	103	103
PRKCQ	-0.078	0.26	-10000	0	-0.52	112	112
LCP2	-0.004	0.097	-10000	0	-0.4	27	27
BCL10	0.017	0.012	-10000	0	-0.25	1	1
regulation of survival gene product expression	-0.037	0.16	-10000	0	-0.32	112	112
IKK complex	0.012	0.059	-10000	0	-0.1	59	59
RAS family/GDP	-0.008	0.015	-10000	0	-0.064	20	20
MAP3K14	-0.029	0.12	-10000	0	-0.25	91	91
PDPK1	-0.042	0.18	-10000	0	-0.36	104	104
TCR/CD3/MHC I/CD8/Fyn	-0.091	0.26	-10000	0	-0.59	91	91

×

IL12-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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.029	0.12	-10000	0	-0.36	29	29
TBX21	-0.3	0.59	-10000	0	-1.3	123	123
B2M	-0.005	0.1	-10000	0	-0.45	25	25
TYK2	0.012	0.022	-10000	0	-10000	0	0
IL12RB1	0.012	0.022	-10000	0	-10000	0	0
GADD45B	-0.18	0.44	-10000	0	-1	96	96
IL12RB2	-0.076	0.16	-10000	0	-0.32	142	142
GADD45G	-0.18	0.43	-10000	0	-1	90	90
natural killer cell activation	-0.005	0.024	-10000	0	-10000	0	0
RELB	0.003	0.078	-10000	0	-0.38	19	19
RELA	0.018	0	-10000	0	-10000	0	0
IL18	-0.046	0.17	-10000	0	-0.44	76	76
IL2RA	-0.03	0.14	-10000	0	-0.4	60	60
IFNG	-0.088	0.17	-10000	0	-0.33	161	161
STAT3 (dimer)	-0.14	0.37	-10000	0	-0.76	112	112
HLA-DRB5	-0.002	0.093	-10000	0	-0.51	17	17
FASLG	-0.24	0.52	-10000	0	-1.1	114	114
NF kappa B2 p52/RelB	-0.24	0.41	-10000	0	-0.86	131	131
CD4	0.015	0.007	-10000	0	-10000	0	0
SOCS1	0.015	0.031	-10000	0	-0.32	4	4
EntrezGene:6955	-0.005	0.012	-10000	0	-10000	0	0
CD3D	-0.033	0.13	-10000	0	-0.35	68	68
CD3E	0.013	0.021	-10000	0	-0.28	2	2
CD3G	-0.097	0.2	-10000	0	-0.42	136	136
IL12Rbeta2/JAK2	-0.048	0.13	-10000	0	-0.33	59	59
CCL3	-0.2	0.44	-10000	0	-0.98	101	101
CCL4	-0.2	0.46	-10000	0	-0.98	110	110
HLA-A	-0.012	0.11	-10000	0	-0.43	34	34
IL18/IL18R	-0.056	0.21	-10000	0	-0.41	117	117
NOS2	-0.19	0.44	-10000	0	-0.82	135	135
IL12/IL12R/TYK2/JAK2/SPHK2	-0.029	0.12	-10000	0	-0.35	31	31
IL1R1	-0.25	0.51	-10000	0	-1.1	127	127
IL4	0.016	0.063	-10000	0	-0.48	7	7
JAK2	0.004	0.06	-10000	0	-0.34	12	12
EntrezGene:6957	-0.004	0.011	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.13	0.33	-10000	0	-0.66	103	103
RAB7A	-0.12	0.34	-10000	0	-0.79	87	87
lysosomal transport	-0.12	0.33	-10000	0	-0.74	88	88
FOS	-0.29	0.5	-10000	0	-1	135	135
STAT4 (dimer)	-0.18	0.43	-10000	0	-0.87	120	120
STAT5A (dimer)	-0.27	0.42	-10000	0	-0.88	138	138
GZMA	-0.2	0.43	-10000	0	-0.85	131	131
GZMB	-0.28	0.57	-10000	0	-1.2	128	128
HLX	0.005	0.079	-10000	0	-0.48	13	13
LCK	-0.25	0.52	-10000	0	-0.98	141	141
TCR/CD3/MHC II/CD4	-0.11	0.23	-10000	0	-0.49	107	107
IL2/IL2R	-0.014	0.14	-10000	0	-0.33	71	71
MAPK14	-0.18	0.44	-10000	0	-0.94	105	105
CCR5	-0.19	0.46	-10000	0	-0.98	105	105
IL1B	-0.053	0.17	-10000	0	-0.42	81	81
STAT6	-0.066	0.18	-10000	0	-0.37	77	77
STAT4	-0.024	0.13	-10000	0	-0.42	50	50
STAT3	0.015	0.04	-10000	0	-0.52	3	3
STAT1	-0.02	0.12	-10000	0	-0.33	58	58
NFKB1	0.017	0.023	-10000	0	-0.52	1	1
NFKB2	0.015	0.031	-10000	0	-0.32	4	4
IL12B	0	0.077	-10000	0	-0.34	21	21
CD8A	-0.001	0.008	-10000	0	-10000	0	0
CD8B	0.001	0.07	-10000	0	-0.28	29	29
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.029	0.12	0.35	29	-10000	0	29
IL2RB	-0.016	0.12	-10000	0	-0.43	40	40
proteasomal ubiquitin-dependent protein catabolic process	-0.16	0.38	-10000	0	-0.78	120	120
IL2RG	-0.002	0.078	-10000	0	-0.28	35	35
IL12	-0.011	0.089	-10000	0	-0.32	19	19
STAT5A	0.011	0.056	-10000	0	-0.42	8	8
CD247	-0.11	0.21	-10000	0	-0.42	153	153
IL2	0.011	0.051	-10000	0	-0.33	10	10
SPHK2	0.017	0.023	-10000	0	-0.52	1	1
FRAP1	0.018	0	-10000	0	-10000	0	0
IL12A	-0.019	0.095	-10000	0	-0.28	55	55
IL12/IL12R/TYK2/JAK2	-0.25	0.54	-10000	0	-1	131	131
MAP2K3	-0.18	0.44	-10000	0	-0.94	108	108
RIPK2	0.013	0.04	-10000	0	-0.28	9	9
MAP2K6	-0.19	0.45	-10000	0	-0.95	110	110
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.002	0.08	-10000	0	-0.52	12	12
IL18RAP	-0.071	0.19	-10000	0	-0.4	114	114
IL12Rbeta1/TYK2	0.018	0.032	-10000	0	-10000	0	0
EOMES	-0.059	0.26	-10000	0	-1.3	21	21
STAT1 (dimer)	-0.2	0.39	-10000	0	-0.78	129	129
T cell proliferation	-0.12	0.31	-10000	0	-0.63	117	117
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.01	0.12	-10000	0	-0.41	37	37
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.2	0.3	-10000	0	-0.69	120	120
ATF2	-0.15	0.4	-10000	0	-0.85	103	103

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.013	0.048	-9999	-0.47	5	5
GNB1/GNG2	-0.11	0.19	-9999	-0.42	103	103
mol:DAG	-0.093	0.18	-9999	-0.44	72	72
PLCG1	-0.096	0.18	-9999	-0.46	72	72
YES1	-0.12	0.2	-9999	-0.45	104	104
FZD3	-0.03	0.15	-9999	-0.48	51	51
FZD6	-0.077	0.2	-9999	-0.45	108	108
G protein	-0.099	0.19	-9999	-0.46	76	76
MAP3K7	-0.068	0.15	-9999	-0.39	61	61
mol:Ca2+	-0.09	0.17	-9999	-0.43	72	72
mol:IP3	-0.093	0.18	-9999	-0.44	72	72
NLK	0.016	0.044	-9999	-0.9	1	1
GNB1	0.013	0.052	-9999	-0.52	5	5
CAMK2A	-0.079	0.16	-9999	-0.42	61	61
MAP3K7IP1	0.018	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.13	0.21	-9999	-0.46	102	102
CSNK1A1	0.017	0.023	-9999	-0.52	1	1
GNAS	-0.12	0.2	-9999	-0.44	104	104
GO:0007205	-0.092	0.17	-9999	-0.43	73	73
WNT6	-0.011	0.087	-9999	-0.26	54	54
WNT4	-0.062	0.18	-9999	-0.45	90	90
NFAT1/CK1 alpha	-0.091	0.19	-9999	-0.48	65	65
GNG2	0.016	0.029	-9999	-0.34	3	3
WNT5A	-0.084	0.2	-9999	-0.43	120	120
WNT11	-0.013	0.089	-9999	-0.26	57	57
CDC42	-0.11	0.2	-9999	-0.42	104	104

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.062	0.17	-9999	-0.44	50	50
NF kappa B1 p50/RelA/I kappa B alpha	-0.043	0.18	-9999	-0.5	41	41
alphaV/beta3 Integrin/Osteopontin/Src	-0.098	0.18	-9999	-0.39	131	131
AP1	-0.15	0.26	-9999	-0.58	105	105
ILK	-0.064	0.16	-9999	-0.42	44	44
bone resorption	-0.055	0.17	-9999	-0.44	44	44
PTK2B	0.017	0.017	-9999	-0.25	2	2
PYK2/p130Cas	-0.059	0.17	-9999	-0.41	54	54
ITGAV	-0.001	0.1	-9999	-0.49	21	21
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.007	0.081	-9999	-0.37	21	21
alphaV/beta3 Integrin/Osteopontin	-0.076	0.18	-9999	-0.34	142	142
MAP3K1	-0.09	0.18	-9999	-0.32	166	166
JUN	-0.034	0.15	-9999	-0.46	57	57
MAPK3	-0.064	0.17	-9999	-0.47	46	46
MAPK1	-0.064	0.17	-9999	-0.47	47	47
Rac1/GDP	0.013	0	-9999	-10000	0	0
NFKB1	0.017	0.023	-9999	-0.52	1	1
MAPK8	-0.08	0.17	-9999	-0.41	67	67
ITGB3	0.003	0.077	-9999	-0.32	25	25
NFKBIA	-0.063	0.19	-9999	-0.52	48	48
FOS	-0.11	0.2	-9999	-0.37	171	171
CD44	-0.004	0.1	-9999	-0.43	26	26
CHUK	0.005	0.081	-9999	-0.5	13	13
PLAU	-0.14	0.38	-9999	-1.2	54	54
NF kappa B1 p50/RelA	-0.047	0.19	-9999	-0.52	45	45
BCAR1	0.017	0.012	-9999	-0.25	1	1
RELA	0.018	0	-9999	-10000	0	0
alphaV beta3 Integrin	0.003	0.1	-9999	-0.42	22	22
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.085	0.18	-9999	-0.32	162	162
VAV3	-0.12	0.2	-9999	-0.43	100	100
MAP3K14	-0.069	0.17	-9999	-0.31	137	137
ROCK2	0.013	0.048	-9999	-0.47	5	5
SPP1	-0.14	0.23	-9999	-0.42	188	188
RAC1	0.018	0	-9999	-10000	0	0
Rac1/GTP	-0.11	0.18	-9999	-0.4	97	97
MMP2	-0.13	0.24	-9999	-0.55	101	101

×

IL23-mediated signaling events

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
CCL2	-0.23	0.53	-10000	0	-1.3	86	86
IL23A	-0.21	0.49	-10000	0	-1.2	68	68
NF kappa B1 p50/RelA/I kappa B alpha	-0.22	0.42	-10000	0	-1	88	88
positive regulation of T cell mediated cytotoxicity	-0.21	0.51	-10000	0	-1.1	91	91
ITGA3	-0.2	0.48	-10000	0	-1.1	80	80
IL17F	-0.097	0.32	-10000	0	-0.68	76	76
IL12B	0.004	0.084	-10000	0	-0.35	21	21
STAT1 (dimer)	-0.21	0.49	-10000	0	-1.1	93	93
CD4	-0.17	0.44	-10000	0	-1	76	76
IL23	-0.2	0.47	-10000	0	-1.2	69	69
IL23R	-0.011	0.18	-10000	0	-1.4	7	7
IL1B	-0.23	0.53	-10000	0	-1.3	80	80
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.18	0.44	-10000	0	-1	74	74
TYK2	0.013	0.024	-10000	0	-10000	0	0
STAT4	-0.024	0.13	-10000	0	-0.42	50	50
STAT3	0.015	0.041	-10000	0	-0.52	3	3
IL18RAP	-0.075	0.18	-10000	0	-0.41	114	114
IL12RB1	0.013	0.024	-10000	0	-10000	0	0
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
IL12Rbeta1/TYK2	0.017	0.031	-10000	0	-10000	0	0
IL23R/JAK2	-0.013	0.19	-10000	0	-1	10	10
positive regulation of chronic inflammatory response	-0.21	0.51	-10000	0	-1.1	91	91
natural killer cell activation	0.001	0.012	0.073	8	-10000	0	8
JAK2	0.011	0.065	-10000	0	-0.34	12	12
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
NFKB1	0.016	0.024	-10000	0	-0.52	1	1
RELA	0.017	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.19	0.45	-10000	0	-1.1	69	69
ALOX12B	-0.17	0.44	-10000	0	-1.1	69	69
CXCL1	-0.27	0.54	-10000	0	-1.1	116	116
T cell proliferation	-0.21	0.51	-10000	0	-1.1	91	91
NFKBIA	0.014	0.043	-10000	0	-0.46	4	4
IL17A	-0.052	0.26	-10000	0	-0.55	55	55
PI3K	-0.19	0.47	-10000	0	-1.1	88	88
IFNG	-0.027	0.05	0.12	2	-0.12	59	61
STAT3 (dimer)	-0.21	0.41	-10000	0	-0.98	92	92
IL18R1	-0.014	0.11	-10000	0	-0.41	37	37
IL23/IL23R/JAK2/TYK2/SOCS3	-0.08	0.28	-10000	0	-0.6	62	62
IL18/IL18R	-0.082	0.2	-10000	0	-0.41	117	117
macrophage activation	-0.015	0.017	-10000	0	-0.044	64	64
TNF	-0.2	0.49	-10000	0	-1.2	76	76
STAT3/STAT4	-0.24	0.45	-10000	0	-1	97	97
STAT4 (dimer)	-0.21	0.5	-10000	0	-1.1	96	96
IL18	-0.05	0.17	-10000	0	-0.44	76	76
IL19	-0.19	0.44	-10000	0	-1.1	70	70
STAT5A (dimer)	-0.2	0.49	-10000	0	-1.1	92	92
STAT1	-0.02	0.12	-10000	0	-0.33	58	58
SOCS3	0.005	0.074	-10000	0	-0.38	17	17
CXCL9	-0.27	0.57	-10000	0	-1.2	122	122
MPO	-0.17	0.44	-10000	0	-1.1	68	68
positive regulation of humoral immune response	-0.21	0.51	-10000	0	-1.1	91	91
IL23/IL23R/JAK2/TYK2	-0.22	0.54	-10000	0	-1.2	91	91
IL6	-0.26	0.55	-10000	0	-1.2	100	100
STAT5A	0.011	0.056	-10000	0	-0.42	8	8
IL2	0.008	0.053	-10000	0	-0.34	10	10
positive regulation of tyrosine phosphorylation of STAT protein	0.001	0.012	0.073	8	-10000	0	8
CD3E	-0.17	0.44	-10000	0	-1	68	68
keratinocyte proliferation	-0.21	0.51	-10000	0	-1.1	91	91
NOS2	-0.18	0.44	-10000	0	-0.96	91	91

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0	0.058	-10000	0	-0.26	23	23
ARNO/beta Arrestin1-2	-0.013	0.089	-10000	0	-0.24	57	57
EGFR	-0.079	0.18	-10000	0	-0.35	139	139
EPHA2	0.008	0.059	-10000	0	-0.33	14	14
USP6	0.012	0.04	-10000	0	-0.25	12	12
IQSEC1	0.016	0.026	-10000	0	-0.39	2	2
EGFR/EGFR/EGF/EGF	-0.15	0.2	-10000	0	-0.42	173	173
ARRB2	0.011	0.052	-10000	0	-0.32	12	12
mol:GTP	0.006	0.015	0.063	11	-0.092	5	16
ARRB1	0.004	0.075	-10000	0	-0.37	18	18
FBXO8	0.015	0.04	-10000	0	-0.52	3	3
TSHR	0.008	0.071	-10000	0	-0.5	10	10
EGF	-0.14	0.23	-10000	0	-0.42	193	193
somatostatin receptor activity	0	0	-10000	0	-0.001	95	95
ARAP2	0	0	-10000	0	0	108	108
mol:GDP	-0.054	0.11	-10000	0	-0.25	89	89
mol:PI-3-4-5-P3	0	0	-10000	0	-0.001	96	96
ITGA2B	0.016	0.02	-10000	0	-0.25	3	3
ARF6	0.016	0.033	-10000	0	-0.52	2	2
Ephrin A1/EPHA2/NCK1/GIT1	0.025	0.071	-10000	0	-0.27	24	24
ADAP1	0	0	-10000	0	0	87	87
KIF13B	-0.002	0.095	-10000	0	-0.43	23	23
HGF/MET	0.007	0.073	-10000	0	-0.38	13	13
PXN	0.018	0	-10000	0	-10000	0	0
ARF6/GTP	-0.067	0.11	-10000	0	-0.27	93	93
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.12	0.18	-10000	0	-0.35	173	173
ADRB2	-0.045	0.16	-10000	0	-0.4	80	80
receptor agonist activity	0	0	-10000	0	0	92	92
actin filament binding	0	0	-10000	0	0	96	96
SRC	0.015	0.035	-10000	0	-0.43	3	3
ITGB3	0.002	0.075	-10000	0	-0.32	25	25
GNAQ	0	0	-10000	0	-0.001	88	88
EFA6/PI-4-5-P2	0	0	-10000	0	-0.001	90	90
ARF6/GDP	-0.003	0.059	-10000	0	-0.3	5	5
ARF6/GDP/GULP/ACAP1	-0.058	0.13	-10000	0	-0.33	74	74
alphaIIb/beta3 Integrin/paxillin/GIT1	0.034	0.048	-10000	0	-0.26	8	8
ACAP1	0	0	-10000	0	0	18	18
ACAP2	0	0	-10000	0	0	104	104
LHCGR/beta Arrestin2	0.009	0.07	-10000	0	-0.44	12	12
EFNA1	0	0.094	-10000	0	-0.49	18	18
HGF	0.008	0.069	-10000	0	-0.45	11	11
CYTH3	0	0	-10000	0	-0.001	94	94
CYTH2	-0.001	0.002	-10000	0	-0.004	100	100
NCK1	0.011	0.045	-10000	0	-0.28	12	12
fibronectin binding	0	0	-10000	0	0	75	75
endosomal lumen acidification	0	0	-10000	0	0	83	83
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	-0.035	0.15	-10000	0	-0.44	61	61
GNAQ/ARNO	-0.001	0.003	-10000	0	-0.006	89	89
mol:Phosphatidic acid	0	0	-10000	0	0	104	104
PIP3-E	0.004	0.068	-10000	0	-0.3	23	23
MET	0	0.075	-10000	0	-0.29	31	31
GNA14	-0.08	0.18	-10000	0	-0.35	140	140
GNA15	0.002	0.076	-10000	0	-0.34	23	23
GIT1	0.014	0.035	-10000	0	-0.3	6	6
mol:PI-4-5-P2	0	0	-10000	0	-0.001	92	92
GNA11	0.013	0.047	-10000	0	-0.52	4	4
LHCGR	0.003	0.083	-10000	0	-0.46	16	16
AGTR1	-0.15	0.21	-10000	0	-0.36	231	231
desensitization of G-protein coupled receptor protein signaling pathway	0.009	0.07	-10000	0	-0.44	12	12
IPCEF1/ARNO	-0.095	0.14	-10000	0	-0.28	179	179
alphaIIb/beta3 Integrin	0.014	0.056	-10000	0	-0.36	7	7

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.015	0.12	-10000	0	-0.38	44	44
GNB1/GNG2	-0.058	0.078	-10000	0	-0.18	138	138
AKT1	-0.023	0.12	-10000	0	-0.21	79	79
EGF	-0.14	0.23	-10000	0	-0.42	193	193
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.03	0.061	-10000	0	-0.29	5	5
mol:Ca2+	-0.048	0.17	-10000	0	-0.29	141	141
LYN	0.029	0.062	-10000	0	-0.29	5	5
RhoA/GTP	-0.041	0.056	-10000	0	-0.13	82	82
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.066	0.19	-10000	0	-0.35	142	142
GNG2	0.016	0.029	-10000	0	-0.34	3	3
ARRB2	0.018	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.004	0.1	-10000	0	-0.39	22	22
G beta5/gamma2	-0.075	0.1	-10000	0	-0.24	137	137
PRKCH	-0.062	0.19	-10000	0	-0.35	139	139
DNM1	0.013	0.047	-10000	0	-0.37	7	7
TXA2/TP beta/beta Arrestin3	0.006	0.019	-10000	0	-0.21	2	2
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	-0.002	0.088	-10000	0	-0.35	29	29
G12 family/GTP	-0.096	0.13	-10000	0	-0.3	141	141
ADRBK1	0.018	0	-10000	0	-10000	0	0
ADRBK2	0.002	0.088	-10000	0	-0.49	16	16
RhoA/GTP/ROCK1	0.016	0.05	-10000	0	-0.31	12	12
mol:GDP	0.019	0.12	0.35	19	-10000	0	19
mol:NADP	0.017	0.012	-10000	0	-0.25	1	1
RAB11A	0.016	0.029	-10000	0	-0.34	3	3
PRKG1	0.017	0.012	-10000	0	-0.25	1	1
mol:IP3	-0.067	0.2	-10000	0	-0.37	141	141
cell morphogenesis	0.016	0.05	-10000	0	-0.31	12	12
PLCB2	-0.1	0.26	-10000	0	-0.5	141	141
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.016	0.073	-10000	0	-0.31	6	6
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.02	0.085	-10000	0	-0.38	12	12
RHOA	0.005	0.08	-10000	0	-0.52	12	12
PTGIR	0.016	0.033	-10000	0	-0.52	2	2
PRKCB1	-0.081	0.22	-10000	0	-0.4	142	142
GNAQ	0	0	-10000	0	-10000	0	0
mol:L-citrulline	0.017	0.012	-10000	0	-0.25	1	1
TXA2/TXA2-R family	-0.11	0.27	-10000	0	-0.52	140	140
LCK	-0.008	0.11	-10000	0	-0.37	16	16
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.034	0.044	-10000	0	-0.36	2	2
TXA2-R family/G12 family/GDP/G beta/gamma	0.029	0.059	-10000	0	-0.53	5	5
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.034	0.044	-10000	0	-0.36	2	2
MAPK14	-0.033	0.13	-10000	0	-0.23	137	137
TGM2/GTP	-0.079	0.23	-10000	0	-0.41	147	147
MAPK11	-0.033	0.13	-10000	0	-0.23	137	137
ARHGEF1	-0.021	0.1	-10000	0	-0.17	136	136
GNAI2	0.006	0.075	-10000	0	-0.48	12	12
JNK cascade	-0.069	0.21	-10000	0	-0.38	140	140
RAB11/GDP	0.016	0.028	-10000	0	-0.34	3	3
ICAM1	-0.052	0.17	-10000	0	-0.3	139	139
cAMP biosynthetic process	-0.063	0.19	-10000	0	-0.34	139	139
Gq family/GTP/EBP50	-0.038	0.11	-10000	0	-0.25	94	94
actin cytoskeleton reorganization	0.016	0.05	-10000	0	-0.31	12	12
SRC	0.029	0.062	-10000	0	-0.29	5	5
GNB5	0.005	0.081	-10000	0	-0.5	13	13
GNB1	0.013	0.052	-10000	0	-0.52	5	5
EGF/EGFR	-0.028	0.11	-10000	0	-0.29	44	44
VCAM1	-0.054	0.17	-10000	0	-0.31	144	144
TP beta/Gq family/GDP/G beta5/gamma2	-0.004	0.1	-10000	0	-0.39	22	22
platelet activation	-0.042	0.17	-10000	0	-0.3	139	139
PGI2/IP	0.012	0.024	-10000	0	-0.38	2	2
PRKACA	0.015	0.046	-10000	0	-0.26	12	12
Gq family/GDP/G beta5/gamma2	-0.005	0.096	-10000	0	-0.36	22	22
TXA2/TP beta/beta Arrestin2	-0.005	0.044	-10000	0	-0.56	3	3
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.021	0.044	-10000	0	-0.24	12	12
mol:DAG	-0.079	0.22	-10000	0	-0.41	140	140
EGFR	-0.079	0.18	-10000	0	-0.35	139	139
TXA2/TP alpha	-0.09	0.25	-10000	0	-0.46	139	139
Gq family/GTP	-0.038	0.078	-10000	0	-0.24	58	58
YES1	0.026	0.07	-10000	0	-0.34	6	6
GNAI2/GTP	-0.015	0.055	-10000	0	-0.33	5	5
PGD2/DP	-0.001	0.062	-10000	0	-0.24	29	29
SLC9A3R1	-0.043	0.16	-10000	0	-0.44	70	70
FYN	0.026	0.073	-10000	0	-0.33	10	10
mol:NO	0.017	0.012	-10000	0	-0.25	1	1
GNA15	0.002	0.076	-10000	0	-0.34	23	23
PGK/cGMP	0.023	0.01	-10000	0	-10000	0	0
RhoA/GDP	0.006	0.079	-10000	0	-0.51	12	12
TP alpha/TGM2/GDP/G beta/gamma	0.028	0.078	-10000	0	-0.37	7	7
NOS3	0.017	0.012	-10000	0	-0.26	1	1
RAC1	0.018	0	-10000	0	-10000	0	0
PRKCA	-0.061	0.19	-10000	0	-0.34	140	140
PRKCB	-0.064	0.19	-10000	0	-0.35	141	141
PRKCE	-0.062	0.19	-10000	0	-0.35	139	139
PRKCD	-0.068	0.2	-10000	0	-0.37	139	139
PRKCG	-0.069	0.2	-10000	0	-0.37	140	140
muscle contraction	-0.095	0.25	-10000	0	-0.48	140	140
PRKCZ	-0.06	0.18	-10000	0	-0.34	140	140
ARR3	0.017	0.012	-10000	0	-0.25	1	1
TXA2/TP beta	0.028	0.059	-10000	0	-0.25	8	8
PRKCQ	-0.068	0.2	-10000	0	-0.35	145	145
MAPKKK cascade	-0.086	0.23	-10000	0	-0.44	141	141
SELE	-0.077	0.2	-10000	0	-0.38	144	144
TP beta/GNAI2/GDP/G beta/gamma	0.038	0.068	-10000	0	-0.37	7	7
ROCK1	0.018	0	-10000	0	-10000	0	0
GNA14	-0.079	0.18	-10000	0	-0.35	140	140
chemotaxis	-0.13	0.31	-10000	0	-0.61	138	138
GNA12	0.018	0	-10000	0	-10000	0	0
GNA13	0.011	0.055	-10000	0	-0.36	10	10
GNA11	0.014	0.047	-10000	0	-0.52	4	4
Rac1/GTP	0.013	0.002	-10000	0	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.011	0.02	-10000	0	-0.24	3	3
GNB1/GNG2	-0.031	0.13	-10000	0	-0.28	107	107
regulation of S phase of mitotic cell cycle	-0.031	0.12	-10000	0	-0.24	120	120
GNAO1	0.016	0.024	-10000	0	-0.25	4	4
HRAS	0.011	0.051	-10000	0	-0.41	7	7
SHBG/T-DHT	0.012	0	-10000	0	-10000	0	0
PELP1	0.017	0.001	-10000	0	-10000	0	0
AKT1	0.008	0.038	-10000	0	-0.26	9	9
MAP2K1	-0.032	0.12	-10000	0	-0.32	32	32
T-DHT/AR	-0.064	0.16	-10000	0	-0.38	104	104
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.005	166	166
GNAI2	0.006	0.075	-10000	0	-0.48	12	12
GNAI3	0.018	0	-10000	0	-10000	0	0
GNAI1	-0.017	0.12	-10000	0	-0.38	46	46
mol:GDP	-0.089	0.17	-10000	0	-0.43	103	103
cell proliferation	-0.066	0.18	-10000	0	-0.4	83	83
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
FOS	-0.13	0.3	-10000	0	-0.78	81	81
mol:Ca2+	-0.014	0.022	-10000	0	-0.06	69	69
MAPK3	-0.05	0.14	-10000	0	-0.42	33	33
MAPK1	-0.029	0.092	-10000	0	-0.27	26	26
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
mol:IP3	-0.001	0.002	-10000	0	-0.003	171	171
cAMP biosynthetic process	0.013	0.021	-10000	0	-10000	0	0
GNG2	0.016	0.029	-10000	0	-0.34	3	3
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.003	171	171
HRAS/GTP	-0.036	0.12	-10000	0	-0.26	107	107
actin cytoskeleton reorganization	-0.01	0.049	-10000	0	-0.24	21	21
SRC	0.015	0.035	-10000	0	-0.43	3	3
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.003	171	171
PI3K	0.006	0.07	-10000	0	-0.31	21	21
apoptosis	0.064	0.17	0.41	82	-10000	0	82
T-DHT/AR/PELP1	-0.044	0.13	-10000	0	-0.32	103	103
HRAS/GDP	-0.063	0.18	-10000	0	-0.4	105	105
CREB1	-0.069	0.18	-10000	0	-0.44	82	82
RAC1-CDC42/GTP	0.02	0.057	-10000	0	-0.24	21	21
AR	-0.089	0.21	-10000	0	-0.52	104	104
GNB1	0.013	0.052	-10000	0	-0.52	5	5
RAF1	-0.033	0.12	-10000	0	-0.25	107	107
RAC1-CDC42/GDP	-0.047	0.17	-10000	0	-0.38	103	103
T-DHT/AR/PELP1/Src	-0.032	0.12	-10000	0	-0.28	105	105
MAP2K2	-0.033	0.12	-10000	0	-0.33	32	32
T-DHT/AR/PELP1/Src/PI3K	-0.032	0.12	-10000	0	-0.24	120	120
GNAZ	0.001	0.088	-10000	0	-0.44	19	19
SHBG	0.018	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.002	0.1	-10000	0	-0.44	15	15
mol:T-DHT	0	0.001	0.002	1	-0.003	52	53
RAC1	0.018	0	-10000	0	-10000	0	0
GNRH1	0	0.057	-10000	0	-0.23	26	26
Gi family/GTP	-0.022	0.092	-10000	0	-0.28	21	21
CDC42	0.018	0	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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
PLK2	-0.049	0.17	-9999	-0.44	77	77
PLK4	0.008	0.065	-9999	-0.38	13	13
regulation of centriole replication	-0.029	0.13	-9999	-0.37	59	59

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.027	0.13	-10000	0	-0.26	110	110
epithelial cell differentiation	-0.007	0.1	-10000	0	-0.26	76	76
CYFIP2	-0.042	0.16	-10000	0	-0.47	65	65
ENAH	0.012	0.096	-10000	0	-0.31	14	14
EGFR	-0.079	0.18	-10000	0	-0.35	139	139
EPHA2	0.008	0.059	-10000	0	-0.33	14	14
MYO6	-0.012	0.11	-10000	0	-0.25	90	90
CTNNB1	0.001	0.09	-10000	0	-0.45	19	19
ABI1/Sra1/Nap1	-0.004	0.11	-10000	0	-0.31	53	53
AQP5	-0.086	0.19	-10000	0	-0.44	97	97
CTNND1	0.016	0.029	-10000	0	-0.34	3	3
mol:PI-4-5-P2	-0.004	0.1	-10000	0	-0.24	78	78
regulation of calcium-dependent cell-cell adhesion	-0.014	0.1	-10000	0	-0.24	82	82
EGF	-0.14	0.23	-10000	0	-0.42	193	193
NCKAP1	0.015	0.031	-10000	0	-0.32	4	4
AQP3	-0.088	0.2	-10000	0	-0.49	86	86
cortical microtubule organization	-0.007	0.1	-10000	0	-0.26	76	76
GO:0000145	-0.006	0.095	-10000	0	-0.23	78	78
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.004	0.11	-10000	0	-0.26	76	76
MLLT4	-0.006	0.11	-10000	0	-0.46	26	26
ARF6/GDP	-0.04	0.086	-10000	0	-0.39	12	12
ARF6	0.016	0.033	-10000	0	-0.52	2	2
Ephrin A1/EPHA2/NCK1/GIT1	0.025	0.071	-10000	0	-0.27	24	24
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.006	0.12	-10000	0	-0.44	15	15
PVRL2	0.002	0.089	-10000	0	-0.52	15	15
ZYX	-0.009	0.11	-10000	0	-0.24	84	84
ARF6/GTP	0.03	0.072	-10000	0	-0.27	22	22
CDH1	-0.049	0.17	-10000	0	-0.48	70	70
EGFR/EGFR/EGF/EGF	-0.14	0.14	-10000	0	-0.38	92	92
RhoA/GDP	-0.01	0.11	-10000	0	-0.25	85	85
actin cytoskeleton organization	-0.007	0.11	-10000	0	-0.38	8	8
IGF-1R heterotetramer	-0.083	0.2	-10000	0	-0.47	110	110
GIT1	0.014	0.035	-10000	0	-0.3	6	6
IGF1R	-0.083	0.2	-10000	0	-0.47	110	110
IGF1	-0.1	0.2	-10000	0	-0.41	146	146
DIAPH1	-0.055	0.18	-10000	0	-0.58	53	53
Wnt receptor signaling pathway	0.007	0.1	0.26	76	-10000	0	76
RHOA	0.005	0.08	-10000	0	-0.52	12	12
RhoA/GTP	-0.044	0.089	-10000	0	-0.37	16	16
CTNNA1	0.017	0.023	-10000	0	-0.52	1	1
VCL	-0.007	0.11	-10000	0	-0.39	8	8
EFNA1	0	0.094	-10000	0	-0.49	18	18
LPP	-0.003	0.1	-10000	0	-0.38	8	8
Ephrin A1/EPHA2	-0.044	0.094	-10000	0	-0.43	8	8
SEC6/SEC8	-0.045	0.092	-10000	0	-0.41	10	10
MGAT3	-0.014	0.11	-10000	0	-0.25	82	82
HGF/MET	-0.044	0.089	-10000	0	-0.34	10	10
HGF	0.008	0.069	-10000	0	-0.45	11	11
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.027	0.13	-10000	0	-0.26	110	110
actin cable formation	0.017	0.1	-10000	0	-0.28	21	21
KIAA1543	0.001	0.1	-10000	0	-0.36	10	10
KIFC3	-0.005	0.1	-10000	0	-0.24	77	77
NCK1	0.011	0.045	-10000	0	-0.28	12	12
EXOC3	0.017	0.012	-10000	0	-0.25	1	1
ACTN1	-0.009	0.11	-10000	0	-0.24	85	85
NCK1/GIT1	0.019	0.042	-10000	0	-0.44	2	2
mol:GDP	-0.007	0.1	-10000	0	-0.26	76	76
EXOC4	0.016	0.033	-10000	0	-0.52	2	2
STX4	-0.003	0.1	-10000	0	-0.24	76	76
PIP5K1C	-0.004	0.1	-10000	0	-0.24	78	78
LIMA1	-0.024	0.14	-10000	0	-0.52	41	41
ABI1	0.016	0.02	-10000	0	-0.25	3	3
ROCK1	0.009	0.1	-10000	0	-0.36	10	10
adherens junction assembly	0.012	0.11	-10000	0	-0.44	8	8
IGF-1R heterotetramer/IGF1	-0.12	0.16	-10000	0	-0.31	166	166
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.002	0.1	-10000	0	-0.39	33	33
MET	0	0.075	-10000	0	-0.29	31	31
PLEKHA7	-0.003	0.099	-10000	0	-0.24	77	77
mol:GTP	0.024	0.07	-10000	0	-0.27	24	24
establishment of epithelial cell apical/basal polarity	0.006	0.11	-10000	0	-0.41	10	10
cortical actin cytoskeleton stabilization	-0.027	0.13	-10000	0	-0.26	110	110
regulation of cell-cell adhesion	-0.007	0.11	-10000	0	-0.38	8	8
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.027	0.13	-10000	0	-0.26	110	110

×

E-cadherin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.02	0.13	-9999	-0.32	78	78
E-cadherin/beta catenin	-0.034	0.14	-9999	-0.38	74	74
CTNNB1	0.001	0.09	-9999	-0.45	19	19
JUP	0.011	0.056	-9999	-0.42	8	8
CDH1	-0.049	0.17	-9999	-0.48	70	70

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.042	0.19	-9999	-0.51	66	66
Syndecan-4/Syndesmos	-0.044	0.21	-9999	-0.51	71	71
positive regulation of JNK cascade	-0.072	0.22	-9999	-0.51	88	88
Syndecan-4/ADAM12	-0.071	0.24	-9999	-0.54	94	94
CCL5	-0.051	0.18	-9999	-0.49	71	71
Rac1/GDP	0.013	0	-9999	-10000	0	0
DNM2	0.017	0.012	-9999	-0.25	1	1
ITGA5	0.015	0.035	-9999	-0.43	3	3
SDCBP	0.003	0.081	-9999	-0.4	19	19
PLG	0.016	0.033	-9999	-0.51	2	2
ADAM12	-0.051	0.17	-9999	-0.47	74	74
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.01	0.063	-9999	-0.49	8	8
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.006	0.012	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.041	0.21	-9999	-0.51	71	71
Syndecan-4/CXCL12/CXCR4	-0.077	0.24	-9999	-0.54	88	88
Syndecan-4/Laminin alpha3	-0.08	0.23	-9999	-0.55	77	77
MDK	-0.016	0.12	-9999	-0.37	46	46
Syndecan-4/FZD7	-0.07	0.23	-9999	-0.53	85	85
Syndecan-4/Midkine	-0.055	0.21	-9999	-0.52	76	76
FZD7	-0.049	0.16	-9999	-0.4	85	85
Syndecan-4/FGFR1/FGF	-0.074	0.22	-9999	-0.49	87	87
THBS1	-0.025	0.14	-9999	-0.52	42	42
integrin-mediated signaling pathway	-0.062	0.22	-9999	-0.51	84	84
positive regulation of MAPKKK cascade	-0.072	0.22	-9999	-0.51	88	88
Syndecan-4/TACI	-0.042	0.2	-9999	-0.51	72	72
CXCR4	-0.028	0.14	-9999	-0.42	55	55
cell adhesion	-0.008	0.1	-9999	-0.29	56	56
Syndecan-4/Dynamin	-0.04	0.2	-9999	-0.51	71	71
Syndecan-4/TSP1	-0.06	0.22	-9999	-0.52	81	81
Syndecan-4/GIPC	-0.042	0.2	-9999	-0.51	71	71
Syndecan-4/RANTES	-0.072	0.23	-9999	-0.55	78	78
ITGB1	0.014	0.044	-9999	-0.41	5	5
LAMA1	0.015	0.026	-9999	-0.25	5	5
LAMA3	-0.07	0.19	-9999	-0.43	103	103
RAC1	0.018	0	-9999	-10000	0	0
PRKCA	0.018	0.05	-9999	-0.23	8	8
Syndecan-4/alpha-Actinin	-0.045	0.21	-9999	-0.52	73	73
TFPI	0.004	0.061	-9999	-0.26	25	25
F2	0.017	0.007	-9999	-10000	0	0
alpha5/beta1 Integrin	0.022	0.041	-9999	-0.37	5	5
positive regulation of cell adhesion	-0.072	0.22	-9999	-0.52	77	77
ACTN1	0.005	0.079	-9999	-0.48	13	13
TNC	-0.039	0.14	-9999	-0.36	79	79
Syndecan-4/CXCL12	-0.067	0.23	-9999	-0.54	82	82
FGF6	0.009	0.066	-9999	-0.52	8	8
RHOA	0.005	0.08	-9999	-0.52	12	12
CXCL12	-0.041	0.16	-9999	-0.47	64	64
TNFRSF13B	0.013	0.035	-9999	-0.25	9	9
FGF2	-0.064	0.16	-9999	-0.34	122	122
FGFR1	-0.013	0.11	-9999	-0.35	44	44
Syndecan-4/PI-4-5-P2	-0.05	0.2	-9999	-0.52	71	71
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.047	0.16	-9999	-0.45	73	73
cell migration	0.002	0.008	-9999	-10000	0	0
PRKCD	0.015	0.041	-9999	-0.44	4	4
vasculogenesis	-0.057	0.21	-9999	-0.5	81	81
SDC4	-0.053	0.22	-9999	-0.55	71	71
Syndecan-4/Tenascin C	-0.065	0.22	-9999	-0.53	84	84
Syndecan-4/PI-4-5-P2/PKC alpha	-0.005	0.009	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.047	0.21	-9999	-0.52	73	73
MMP9	-0.04	0.17	-9999	-0.5	60	60
Rac1/GTP	-0.008	0.1	-9999	-0.3	56	56
cytoskeleton organization	-0.041	0.2	-9999	-0.49	71	71
GIPC1	0.014	0.042	-9999	-0.45	4	4
Syndecan-4/TFPI	-0.046	0.21	-9999	-0.51	73	73

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.1	0.26	-10000	0	-0.62	82	82
IHH	-0.014	0.093	-10000	0	-0.48	14	14
SHH Np/Cholesterol/GAS1	-0.057	0.14	-10000	0	-0.29	133	133
LRPAP1	0.016	0.026	-10000	0	-0.39	2	2
dorsoventral neural tube patterning	0.056	0.14	0.29	133	-10000	0	133
SMO/beta Arrestin2	-0.055	0.17	-10000	0	-0.51	37	37
SMO	-0.066	0.18	-10000	0	-0.55	37	37
AKT1	-0.027	0.13	-10000	0	-0.52	21	21
ARRB2	0.018	0	-10000	0	-10000	0	0
BOC	-0.02	0.12	-10000	0	-0.38	50	50
ADRBK1	0.018	0	-10000	0	-10000	0	0
heart looping	-0.065	0.18	-10000	0	-0.54	37	37
STIL	-0.052	0.15	-10000	0	-0.37	52	52
DHH N/PTCH2	0.026	0	-10000	0	-10000	0	0
DHH N/PTCH1	-0.028	0.13	-10000	0	-0.37	24	24
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
DHH	0.018	0	-10000	0	-10000	0	0
PTHLH	-0.12	0.31	-10000	0	-0.83	66	66
determination of left/right symmetry	-0.065	0.18	-10000	0	-0.54	37	37
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
skeletal system development	-0.12	0.31	-10000	0	-0.82	66	66
IHH N/Hhip	0.004	0.068	-10000	0	-0.29	22	22
DHH N/Hhip	0.021	0.037	-10000	0	-0.37	3	3
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.065	0.18	-10000	0	-0.54	37	37
pancreas development	0.011	0.052	-10000	0	-0.33	11	11
HHAT	-0.045	0.17	-10000	0	-0.51	63	63
PI3K	0.005	0.082	-10000	0	-0.37	21	21
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.072	0.19	-10000	0	-0.47	98	98
somite specification	-0.065	0.18	-10000	0	-0.54	37	37
SHH Np/Cholesterol/PTCH1	-0.049	0.14	-10000	0	-0.37	44	44
SHH Np/Cholesterol/PTCH2	-0.007	0.098	-10000	0	-0.28	61	61
SHH Np/Cholesterol/Megalin	-0.1	0.18	-10000	0	-0.33	181	181
SHH	-0.021	0.13	-10000	0	-0.37	61	61
catabolic process	-0.042	0.14	-10000	0	-0.42	24	24
SMO/Vitamin D3	-0.061	0.17	-10000	0	-0.46	40	40
SHH Np/Cholesterol/Hhip	-0.01	0.1	-10000	0	-0.28	64	64
LRP2	-0.16	0.24	-10000	0	-0.48	183	183
receptor-mediated endocytosis	-0.12	0.2	-10000	0	-0.49	74	74
SHH Np/Cholesterol/BOC	-0.027	0.12	-10000	0	-0.28	85	85
SHH Np/Cholesterol/CDO	-0.019	0.11	-10000	0	-0.29	74	74
mesenchymal cell differentiation	0.011	0.1	0.28	64	-10000	0	64
mol:Vitamin D3	-0.047	0.14	-10000	0	-0.37	44	44
IHH N/PTCH2	0.01	0.055	-10000	0	-0.32	11	11
CDON	-0.004	0.099	-10000	0	-0.41	27	27
IHH N/PTCH1	-0.04	0.14	-10000	0	-0.42	24	24
Megalin/LRPAP1	-0.1	0.18	-10000	0	-0.37	158	158
PTCH2	0.018	0	-10000	0	-10000	0	0
SHH Np/Cholesterol	-0.017	0.097	-10000	0	-0.28	61	61
PTCH1	-0.043	0.14	-10000	0	-0.42	24	24
HHIP	0.011	0.052	-10000	0	-0.33	11	11

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.065	0.13	-9999	-0.32	63	63
SMAD6-7/SMURF1	0.034	0.021	-9999	-0.3	1	1
NOG	0.009	0.056	-9999	-0.31	14	14
SMAD9	-0.023	0.12	-9999	-0.65	12	12
SMAD4	0.009	0.067	-9999	-0.49	9	9
SMAD5	-0.062	0.14	-9999	-0.38	56	56
BMP7/USAG1	-0.18	0.18	-9999	-0.39	202	202
SMAD5/SKI	-0.051	0.14	-9999	-0.39	43	43
SMAD1	0.024	0.061	-9999	-0.37	7	7
BMP2	-0.019	0.11	-9999	-0.32	58	58
SMAD1/SMAD1/SMAD4	-0.01	0.044	-9999	-0.33	3	3
BMPR1A	0.009	0.068	-9999	-0.47	10	10
BMPR1B	-0.11	0.16	-9999	-0.29	216	216
BMPR1A-1B/BAMBI	-0.13	0.17	-9999	-0.36	157	157
AHSG	0.016	0.024	-9999	-0.25	4	4
CER1	0.017	0.012	-9999	-0.25	1	1
BMP2-4/CER1	-0.052	0.14	-9999	-0.35	84	84
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.053	0.14	-9999	-0.38	43	43
BMP2-4 (homodimer)	-0.075	0.16	-9999	-0.42	83	83
RGMB	0.009	0.07	-9999	-0.52	9	9
BMP6/BMPR2/BMPR1A-1B	-0.042	0.11	-9999	-0.3	53	53
RGMA	-0.027	0.12	-9999	-0.3	75	75
SMURF1	0.018	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.072	0.14	-9999	-0.32	96	96
BMP2-4/USAG1	-0.2	0.2	-9999	-0.38	245	245
SMAD6/SMURF1/SMAD5	-0.051	0.14	-9999	-0.39	41	41
SOSTDC1	-0.23	0.23	-9999	-0.39	314	314
BMP7/BMPR2/BMPR1A-1B	-0.06	0.12	-9999	-0.3	68	68
SKI	0.017	0.017	-9999	-0.25	2	2
BMP6 (homodimer)	-0.006	0.089	-9999	-0.3	40	40
HFE2	0.004	0.08	-9999	-0.45	15	15
ZFYVE16	0.016	0.033	-9999	-0.52	2	2
MAP3K7	0.016	0.02	-9999	-0.25	3	3
BMP2-4/CHRD	-0.059	0.16	-9999	-0.37	84	84
SMAD5/SMAD5/SMAD4	-0.055	0.14	-9999	-0.39	45	45
MAPK1	0.016	0.033	-9999	-0.52	2	2
TAK1/TAB family	-0.032	0.13	-9999	-0.43	25	25
BMP7 (homodimer)	-0.041	0.13	-9999	-0.29	101	101
NUP214	0.016	0.026	-9999	-0.39	2	2
BMP6/FETUA	0.008	0.065	-9999	-0.36	8	8
SMAD1/SKI	0.032	0.06	-9999	-0.34	7	7
SMAD6	0.016	0.024	-9999	-0.25	4	4
CTDSP2	0.014	0.044	-9999	-0.41	5	5
BMP2-4/FETUA	-0.053	0.14	-9999	-0.35	84	84
MAP3K7IP1	0.018	0	-9999	-10000	0	0
GREM1	-0.038	0.16	-9999	-0.45	63	63
BMPR2 (homodimer)	0.016	0.033	-9999	-0.52	2	2
GADD34/PP1CA	0.03	0.04	-9999	-0.3	5	5
BMPR1A-1B (homodimer)	-0.068	0.12	-9999	-0.38	39	39
CHRDL1	-0.013	0.09	-9999	-0.27	56	56
ENDOFIN/SMAD1	0.032	0.063	-9999	-0.36	8	8
SMAD6-7/SMURF1/SMAD1	0.046	0.058	-9999	-0.37	3	3
SMAD6/SMURF1	0.018	0	-9999	-10000	0	0
BAMBI	-0.13	0.22	-9999	-0.41	182	182
SMURF2	0.009	0.058	-9999	-0.34	13	13
BMP2-4/CHRDL1	-0.068	0.16	-9999	-0.36	97	97
BMP2-4/GREM1	-0.085	0.18	-9999	-0.37	119	119
SMAD7	0.016	0.026	-9999	-0.39	2	2
SMAD8A/SMAD8A/SMAD4	-0.016	0.11	-9999	-0.47	20	20
SMAD1/SMAD6	0.033	0.06	-9999	-0.34	7	7
TAK1/SMAD6	0.025	0.014	-9999	-10000	0	0
BMP7	-0.041	0.13	-9999	-0.29	101	101
BMP6	-0.006	0.089	-9999	-0.3	40	40
MAP3K7IP2	0.014	0.047	-9999	-0.52	4	4
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.052	0.13	-9999	-0.37	40	40
PPM1A	0.016	0.026	-9999	-0.39	2	2
SMAD1/SMURF2	0.029	0.067	-9999	-0.35	8	8
SMAD7/SMURF1	0.025	0.019	-9999	-0.37	1	1
CTDSPL	0.011	0.062	-9999	-0.52	7	7
PPP1CA	0.011	0.048	-9999	-0.3	11	11
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0.016	0.033	-9999	-0.52	2	2
PPP1R15A	0.016	0.029	-9999	-0.34	3	3
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.081	0.16	-9999	-0.36	89	89
CHRD	0.003	0.073	-9999	-0.33	22	22
BMPR2	0.016	0.033	-9999	-0.52	2	2
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.074	0.15	-9999	-0.33	96	96
BMP4	-0.092	0.19	-9999	-0.39	143	143
FST	-0.017	0.11	-9999	-0.32	54	54
BMP2-4/NOG	-0.056	0.15	-9999	-0.35	88	88
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.048	0.11	-9999	-0.3	53	53

×

ErbB4 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.1	0.3	-10000	0	-0.91	53	53
epithelial cell differentiation	-0.1	0.23	-10000	0	-0.72	56	56
ITCH	0.019	0.028	-10000	0	-10000	0	0
WWP1	-0.13	0.4	-10000	0	-1.4	44	44
FYN	0.008	0.067	-10000	0	-0.41	12	12
EGFR	-0.079	0.18	-10000	0	-0.35	139	139
PRL	0.015	0.031	-10000	0	-0.32	4	4
neuron projection morphogenesis	-0.032	0.22	-10000	0	-0.71	45	45
PTPRZ1	-0.028	0.11	-10000	0	-0.29	79	79
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.047	0.25	-10000	0	-0.82	45	45
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.08	0.27	-10000	0	-0.93	45	45
ADAM17	0.017	0.037	-10000	0	-0.26	4	4
ErbB4/ErbB4	-0.11	0.32	-10000	0	-0.99	52	52
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.1	0.3	-10000	0	-0.88	56	56
NCOR1	0.016	0.033	-10000	0	-0.52	2	2
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.073	0.26	-10000	0	-0.88	46	46
GRIN2B	-0.074	0.25	-10000	0	-0.82	47	47
ErbB4/ErbB2/betacellulin	-0.12	0.28	-10000	0	-0.73	71	71
STAT1	-0.02	0.12	-10000	0	-0.33	58	58
HBEGF	0.005	0.072	-10000	0	-0.36	18	18
PRLR	-0.03	0.15	-10000	0	-0.49	50	50
E4ICDs/ETO2	-0.17	0.34	-10000	0	-0.79	89	89
axon guidance	-0.079	0.28	-10000	0	-0.91	47	47
NEDD4	0.003	0.095	-10000	0	-0.53	15	15
Prolactin receptor/Prolactin receptor/Prolactin	-0.01	0.11	-10000	0	-0.37	45	45
CBFA2T3	-0.13	0.23	-10000	0	-0.45	162	162
ErbB4/ErbB2/HBEGF	-0.091	0.27	-10000	0	-0.81	54	54
MAPK3	-0.04	0.23	-10000	0	-0.75	45	45
STAT1 (dimer)	-0.11	0.3	-10000	0	-0.9	56	56
MAPK1	-0.04	0.23	-10000	0	-0.75	45	45
JAK2	0.01	0.053	-10000	0	-0.32	12	12
ErbB4/ErbB2/neuregulin 1 beta	-0.09	0.27	-10000	0	-0.83	52	52
NRG1	0.018	0.047	-10000	0	-0.36	3	3
NRG3	0	0.081	-10000	0	-0.34	26	26
NRG2	-0.017	0.1	-10000	0	-0.3	57	57
NRG4	0.009	0.051	-10000	0	-0.27	16	16
heart development	-0.079	0.28	-10000	0	-0.91	47	47
neural crest cell migration	-0.088	0.26	-10000	0	-0.82	52	52
ERBB2	-0.007	0.088	-10000	0	-0.35	18	18
WWOX/E4ICDs	-0.1	0.29	-10000	0	-0.91	52	52
SHC1	0.017	0.023	-10000	0	-0.52	1	1
ErbB4/EGFR/neuregulin 4	-0.13	0.31	-10000	0	-0.85	63	63
apoptosis	0.097	0.28	0.9	49	-10000	0	49
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.11	0.31	-10000	0	-0.92	55	55
ErbB4/ErbB2/epiregulin	-0.1	0.27	-10000	0	-0.81	55	55
ErbB4/ErbB4/betacellulin/betacellulin	-0.13	0.3	-10000	0	-0.88	60	60
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.088	0.29	-10000	0	-0.72	74	74
MDM2	-0.096	0.3	-10000	0	-0.92	52	52
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.062	0.25	-10000	0	-0.84	44	44
STAT5A	-0.072	0.27	-10000	0	-0.88	47	47
ErbB4/EGFR/neuregulin 1 beta	-0.11	0.28	-10000	0	-0.8	61	61
DLG4	0.018	0	-10000	0	-10000	0	0
GRB2/SHC	0.024	0.023	-10000	0	-0.37	1	1
E4ICDs/TAB2/NCoR1	-0.081	0.28	-10000	0	-0.93	47	47
STAT5A (dimer)	-0.11	0.26	-10000	0	-0.81	56	56
MAP3K7IP2	0.014	0.047	-10000	0	-0.52	4	4
STAT5B (dimer)	-0.068	0.27	-10000	0	-0.86	48	48
LRIG1	-0.032	0.15	-10000	0	-0.48	53	53
EREG	-0.024	0.11	-10000	0	-0.28	74	74
BTC	-0.05	0.17	-10000	0	-0.42	82	82
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.081	0.28	-10000	0	-0.93	47	47
ERBB4	-0.11	0.32	-10000	0	-1	52	52
STAT5B	0.016	0.026	-10000	0	-0.39	2	2
YAP1	-0.014	0.1	-10000	0	-0.71	6	6
GRB2	0.016	0.024	-10000	0	-0.25	4	4
ErbB4/ErbB2/neuregulin 4	-0.088	0.27	-10000	0	-0.83	52	52
glial cell differentiation	0.079	0.28	0.91	47	-10000	0	47
WWOX	-0.003	0.072	-10000	0	-0.25	40	40
cell proliferation	-0.1	0.27	-10000	0	-0.81	54	54

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.005	0.13	-10000	0	-0.46	25	25
UGCG	-0.11	0.27	-10000	0	-0.77	74	74
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.07	0.19	-10000	0	-0.38	100	100
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.11	0.27	-10000	0	-0.76	74	74
mol:DAG	-0.014	0.12	-10000	0	-0.95	8	8
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.14	0.2	-10000	0	-0.42	149	149
FRAP1	-0.12	0.26	-10000	0	-0.47	159	159
FOXO3	-0.064	0.19	-10000	0	-0.4	89	89
AKT1	-0.073	0.21	-10000	0	-0.43	93	93
GAB2	0.007	0.048	-10000	0	-0.25	17	17
SMPD1	-0.004	0.079	-10000	0	-0.8	4	4
SGMS1	-0.01	0.099	-10000	0	-0.73	8	8
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	0.069	-10000	0	-0.31	21	21
CALM1	0.018	0	-10000	0	-10000	0	0
cell proliferation	-0.088	0.2	-10000	0	-0.42	119	119
EIF3A	0.017	0.012	-10000	0	-0.25	1	1
PI3K	0.006	0.083	-10000	0	-0.37	21	21
RPS6KB1	-0.034	0.1	-10000	0	-0.24	62	62
mol:sphingomyelin	-0.014	0.12	-10000	0	-0.95	8	8
natural killer cell activation	-0.002	0.004	-10000	0	-0.013	30	30
JAK3	0.018	0.004	-10000	0	-10000	0	0
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
JAK1	0.012	0.057	-10000	0	-0.52	6	6
NFKB1	0.017	0.023	-10000	0	-0.52	1	1
MYC	-0.091	0.28	-10000	0	-0.81	50	50
MYB	-0.23	0.5	-10000	0	-1.2	108	108
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.043	0.16	-10000	0	-0.36	66	66
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.014	0.099	-10000	0	-0.38	4	4
mol:PI-3-4-5-P3	-0.042	0.16	-10000	0	-0.35	66	66
Rac1/GDP	0.011	0.064	-10000	0	-0.28	21	21
T cell proliferation	-0.038	0.15	-10000	0	-0.33	66	66
SHC1	0.015	0.024	-10000	0	-0.52	1	1
RAC1	0.017	0.001	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.009	0.029	-10000	0	-0.061	118	118
PRKCZ	-0.04	0.15	-10000	0	-0.34	66	66
NF kappa B1 p50/RelA	-0.085	0.23	-10000	0	-0.46	108	108
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.016	0.14	-10000	0	-0.49	28	28
HSP90AA1	0.013	0.045	-10000	0	-0.39	6	6
RELA	0.018	0	-10000	0	-10000	0	0
IL2RA	-0.032	0.14	-10000	0	-0.41	60	60
IL2RB	-0.016	0.12	-10000	0	-0.43	40	40
TERT	0.013	0.042	-10000	0	-0.33	7	7
E2F1	-0.076	0.19	-10000	0	-0.44	113	113
SOS1	0.015	0.024	-10000	0	-0.53	1	1
RPS6	0.015	0.037	-10000	0	-0.39	4	4
mol:cAMP	0.004	0.014	0.029	119	-10000	0	119
PTPN11	0.015	0.024	-10000	0	-0.52	1	1
IL2RG	-0.002	0.078	-10000	0	-0.28	35	35
actin cytoskeleton organization	-0.038	0.15	-10000	0	-0.33	66	66
GRB2	0.014	0.024	-10000	0	-0.25	4	4
IL2	0.011	0.051	-10000	0	-0.33	10	10
PIK3CA	0.016	0.03	-10000	0	-0.35	3	3
Rac1/GTP	0.013	0.064	-10000	0	-0.26	21	21
LCK	-0.073	0.18	-10000	0	-0.4	117	117
BCL2	-0.19	0.39	-10000	0	-0.83	129	129

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.029	0.15	-9999	-0.39	65	65
alphaM/beta2 Integrin/GPIbA	-0.011	0.11	-9999	-0.33	42	42
alphaM/beta2 Integrin/proMMP-9	-0.036	0.15	-9999	-0.36	83	83
PLAUR	-0.016	0.13	-9999	-0.47	37	37
HMGB1	0.011	0.021	-9999	-0.27	1	1
alphaM/beta2 Integrin/Talin	0	0.1	-9999	-0.36	31	31
AGER	0.01	0.031	-9999	-0.39	2	2
RAP1A	0.012	0.057	-9999	-0.52	6	6
SELPLG	-0.003	0.097	-9999	-0.43	24	24
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.012	0.13	-9999	-0.36	39	39
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.042	0.17	-9999	-0.51	60	60
CYR61	-0.042	0.16	-9999	-0.42	72	72
TLN1	0.017	0.023	-9999	-0.52	1	1
Rap1/GTP	-0.036	0.1	-9999	-0.42	26	26
RHOA	0.005	0.08	-9999	-0.52	12	12
P-selectin oligomer	-0.12	0.22	-9999	-0.44	156	156
MYH2	-0.003	0.13	-9999	-0.41	29	29
MST1R	-0.039	0.16	-9999	-0.51	57	57
leukocyte activation during inflammatory response	0.008	0.086	-9999	-0.31	30	30
APOB	0.018	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.032	0.15	-9999	-0.47	54	54
JAM3	-0.006	0.11	-9999	-0.5	24	24
GP1BA	-0.002	0.071	-9999	-0.25	39	39
alphaM/beta2 Integrin/CTGF	-0.031	0.14	-9999	-0.39	59	59
alphaM/beta2 Integrin	-0.008	0.13	-9999	-0.43	29	29
JAM3 homodimer	-0.006	0.11	-9999	-0.5	24	24
ICAM2	0.007	0.068	-9999	-0.4	13	13
ICAM1	-0.019	0.12	-9999	-0.39	47	47
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.008	0.13	-9999	-0.43	29	29
cell adhesion	-0.011	0.11	-9999	-0.33	42	42
NFKB1	-0.032	0.17	-9999	-0.38	76	76
THY1	-0.007	0.11	-9999	-0.5	25	25
RhoA/GDP	0.004	0.058	-9999	-0.38	12	12
Lipoprotein(a)	0.023	0.016	-9999	-0.31	1	1
alphaM/beta2 Integrin/LRP/tPA	-0.049	0.14	-9999	-0.32	93	93
IL6	-0.087	0.27	-9999	-0.71	71	71
ITGB2	-0.022	0.12	-9999	-0.43	40	40
elevation of cytosolic calcium ion concentration	-0.044	0.18	-9999	-0.41	82	82
alphaM/beta2 Integrin/JAM2/JAM3	-0.02	0.15	-9999	-0.38	64	64
JAM2	-0.019	0.13	-9999	-0.43	43	43
alphaM/beta2 Integrin/ICAM1	-0.028	0.16	-9999	-0.33	91	91
alphaM/beta2 Integrin/uPA/Plg	-0.027	0.14	-9999	-0.34	75	75
RhoA/GTP	-0.008	0.14	-9999	-0.44	30	30
positive regulation of phagocytosis	-0.007	0.16	-9999	-0.46	42	42
Ron/MSP	-0.017	0.12	-9999	-0.37	55	55
alphaM/beta2 Integrin/uPAR/uPA	-0.044	0.18	-9999	-0.41	82	82
alphaM/beta2 Integrin/uPAR	-0.019	0.14	-9999	-0.39	53	53
PLAU	-0.052	0.17	-9999	-0.43	83	83
PLAT	-0.093	0.19	-9999	-0.37	150	150
actin filament polymerization	-0.001	0.13	-9999	-0.4	29	29
MST1	0.016	0.02	-9999	-0.25	3	3
alphaM/beta2 Integrin/lipoprotein(a)	0.011	0.088	-9999	-0.31	30	30
TNF	-0.035	0.19	-9999	-0.61	32	32
RAP1B	0.013	0.044	-9999	-0.32	8	8
alphaM/beta2 Integrin/uPA	-0.041	0.15	-9999	-0.37	75	75
fibrinolysis	-0.028	0.14	-9999	-0.34	75	75
HCK	-0.005	0.11	-9999	-0.47	25	25
dendritic cell antigen processing and presentation	-0.008	0.13	-9999	-0.43	29	29
VTN	0.016	0.02	-9999	-0.25	3	3
alphaM/beta2 Integrin/CYR61	-0.035	0.14	-9999	-0.36	70	70
LPA	0.016	0.026	-9999	-0.39	2	2
LRP1	0.017	0.023	-9999	-0.52	1	1
cell migration	-0.051	0.18	-9999	-0.36	107	107
FN1	-0.048	0.17	-9999	-0.46	73	73
alphaM/beta2 Integrin/Thy1	-0.014	0.12	-9999	-0.36	50	50
MPO	0.008	0.05	-9999	-0.25	19	19
KNG1	0.017	0.017	-9999	-0.25	2	2
RAP1/GDP	0.017	0.044	-9999	-0.31	8	8
ROCK1	0	0.13	-9999	-0.41	29	29
ELA2	0.017	0.017	-9999	-0.25	2	2
PLG	0.016	0.033	-9999	-0.52	2	2
CTGF	-0.035	0.15	-9999	-0.42	63	63
alphaM/beta2 Integrin/Hck	-0.012	0.14	-9999	-0.43	42	42
ITGAM	0.002	0.071	-9999	-0.48	10	10
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.072	0.18	-9999	-0.34	132	132
HP	0.013	0.049	-9999	-0.43	6	6
leukocyte adhesion	-0.034	0.18	-9999	-0.54	43	43
SELP	-0.12	0.22	-9999	-0.44	156	156

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	-0.008	0.11	-10000	0	-0.4	33	33
EPHB2	0.008	0.062	-10000	0	-0.32	16	16
EFNB1	0.017	0.051	-10000	0	-0.4	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.021	0.082	-10000	0	-0.34	9	9
Ephrin B2/EPHB1-2	-0.006	0.089	-10000	0	-0.28	34	34
neuron projection morphogenesis	-0.023	0.061	-10000	0	-0.31	10	10
Ephrin B1/EPHB1-2/Tiam1	0.015	0.087	-10000	0	-0.29	22	22
DNM1	0.013	0.047	-10000	0	-0.37	7	7
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.084	0.23	-10000	0	-0.59	84	84
YES1	-0.13	0.3	-10000	0	-0.84	81	81
Ephrin B1/EPHB1-2/NCK2	0.019	0.078	-10000	0	-0.28	17	17
PI3K	-0.081	0.24	-10000	0	-0.6	83	83
mol:GDP	0.013	0.086	-10000	0	-0.29	22	22
ITGA2B	0.016	0.02	-10000	0	-0.25	3	3
endothelial cell proliferation	-0.01	0.1	-10000	0	-0.33	40	40
FYN	-0.13	0.3	-10000	0	-0.83	81	81
MAP3K7	-0.084	0.23	-10000	0	-0.63	81	81
FGR	-0.11	0.3	-10000	0	-0.82	81	81
TIAM1	0.006	0.073	-10000	0	-0.44	13	13
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
RGS3	0.017	0.012	-10000	0	-0.25	1	1
cell adhesion	-0.069	0.22	-10000	0	-0.56	82	82
LYN	-0.12	0.3	-10000	0	-0.83	81	81
Ephrin B1/EPHB1-2/Src Family Kinases	-0.12	0.28	-10000	0	-0.77	81	81
Ephrin B1/EPHB1-2	-0.11	0.25	-10000	0	-0.68	81	81
SRC	-0.11	0.3	-10000	0	-0.82	81	81
ITGB3	0.002	0.075	-10000	0	-0.32	25	25
EPHB1	-0.022	0.1	-10000	0	-0.28	72	72
EPHB4	-0.013	0.12	-10000	0	-0.43	36	36
RAC1	0.018	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.01	0.1	-10000	0	-0.34	40	40
alphaIIb/beta3 Integrin	0.014	0.056	-10000	0	-0.36	7	7
BLK	-0.13	0.3	-10000	0	-0.83	81	81
HCK	-0.13	0.3	-10000	0	-0.83	81	81
regulation of stress fiber formation	-0.018	0.076	0.28	17	-10000	0	17
MAPK8	-0.074	0.22	-10000	0	-0.56	82	82
Ephrin B1/EPHB1-2/RGS3	0.02	0.075	-10000	0	-0.27	15	15
endothelial cell migration	-0.09	0.22	-10000	0	-0.53	92	92
NCK2	0.015	0.026	-10000	0	-0.25	5	5
PTPN13	-0.089	0.24	-10000	0	-0.64	81	81
regulation of focal adhesion formation	-0.018	0.076	0.28	17	-10000	0	17
chemotaxis	-0.019	0.074	0.27	15	-10000	0	15
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
Rac1/GTP	0.015	0.078	-10000	0	-0.33	9	9
angiogenesis	-0.11	0.24	-10000	0	-0.68	81	81
LCK	-0.14	0.31	-10000	0	-0.84	81	81

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.005	0.08	-9999	-0.24	48	48
NF kappa B1 p50/RelA/I kappa B alpha	0.003	0.086	-9999	-0.31	14	14
AP1	-0.092	0.14	-9999	-0.3	133	133
mol:PIP3	-0.067	0.11	-9999	-0.28	85	85
AKT1	0.007	0.11	-9999	-0.36	24	24
PTK2B	-0.009	0.064	-9999	-0.2	47	47
RHOA	-0.007	0.093	-9999	-0.41	17	17
PIK3CB	0.012	0.055	-9999	-0.44	7	7
mol:Ca2+	-0.025	0.094	-9999	-0.26	61	61
MAGI3	-0.014	0.12	-9999	-0.46	35	35
RELA	0.018	0	-9999	-10000	0	0
apoptosis	-0.004	0.067	-9999	-0.22	44	44
HRAS/GDP	0.009	0.036	-9999	-0.29	7	7
positive regulation of microtubule depolymerization	-0.045	0.12	-9999	-0.26	116	116
NF kappa B1 p50/RelA	-0.04	0.092	-9999	-0.32	30	30
endothelial cell migration	-0.036	0.18	-9999	-0.55	54	54
ADCY4	-0.005	0.11	-9999	-0.3	48	48
ADCY5	-0.014	0.11	-9999	-0.31	48	48
ADCY6	-0.004	0.1	-9999	-0.29	47	47
ADCY7	-0.007	0.11	-9999	-0.32	47	47
ADCY1	-0.003	0.1	-9999	-0.29	47	47
ADCY2	-0.025	0.12	-9999	-0.35	51	51
ADCY3	-0.006	0.1	-9999	-0.29	49	49
ADCY8	-0.005	0.1	-9999	-0.29	47	47
ADCY9	-0.01	0.11	-9999	-0.29	48	48
GSK3B	-0.002	0.061	-9999	-0.18	44	44
arachidonic acid secretion	0.001	0.1	-9999	-0.28	49	49
GNG2	0.016	0.029	-9999	-0.34	3	3
TRIP6	0	0.088	-9999	-0.4	23	23
GNAO1	-0.004	0.078	-9999	-0.25	44	44
HRAS	0.012	0.051	-9999	-0.41	7	7
NFKBIA	-0.014	0.091	-9999	-0.3	23	23
GAB1	0.006	0.074	-9999	-0.43	14	14
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0.006	0.15	-9999	-0.89	15	15
JUN	-0.034	0.15	-9999	-0.46	57	57
LPA/LPA2/NHERF2	-0.024	0.1	-9999	-0.31	52	52
TIAM1	-0.025	0.18	-9999	-1	15	15
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
mol:IP3	-0.025	0.095	-9999	-0.26	61	61
PLCB3	-0.016	0.094	-9999	-0.3	49	49
FOS	-0.11	0.2	-9999	-0.37	171	171
positive regulation of mitosis	0.001	0.1	-9999	-0.28	49	49
LPA/LPA1-2-3	-0.015	0.068	-9999	-0.21	54	54
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.017	0.012	-9999	-0.25	1	1
stress fiber formation	0.001	0.063	-9999	-0.19	45	45
GNAZ	-0.013	0.096	-9999	-0.28	55	55
EGFR/PI3K-beta/Gab1	-0.069	0.12	-9999	-0.3	85	85
positive regulation of dendritic cell cytokine production	-0.015	0.068	-9999	-0.21	54	54
LPA/LPA2/MAGI-3	-0.013	0.08	-9999	-0.28	35	35
ARHGEF1	0.009	0.074	-9999	-0.22	36	36
GNAI2	-0.01	0.095	-9999	-0.29	49	49
GNAI3	-0.003	0.077	-9999	-0.25	44	44
GNAI1	-0.023	0.11	-9999	-0.31	58	58
LPA/LPA3	-0.011	0.033	-9999	-0.11	54	54
LPA/LPA2	-0.011	0.033	-9999	-0.1	54	54
LPA/LPA1	-0.019	0.09	-9999	-0.28	54	54
HB-EGF/EGFR	-0.069	0.16	-9999	-0.35	104	104
HBEGF	-0.027	0.13	-9999	-0.38	64	64
mol:DAG	-0.025	0.095	-9999	-0.26	61	61
cAMP biosynthetic process	-0.007	0.11	-9999	-0.3	51	51
NFKB1	0.017	0.023	-9999	-0.52	1	1
SRC	0.015	0.035	-9999	-0.43	3	3
GNB1	0.013	0.052	-9999	-0.52	5	5
LYN	-0.013	0.088	-9999	-0.27	29	29
GNAQ	-0.005	0.027	-9999	-0.082	54	54
LPAR2	0	0.001	-9999	-10000	0	0
LPAR3	0	0.001	-9999	-10000	0	0
LPAR1	-0.012	0.052	-9999	-0.16	54	54
IL8	-0.13	0.19	-9999	-0.41	122	122
PTK2	-0.003	0.067	-9999	-0.21	45	45
Rac1/GDP	0.013	0	-9999	-10000	0	0
CASP3	-0.004	0.068	-9999	-0.22	44	44
EGFR	-0.079	0.18	-9999	-0.35	139	139
PLCG1	-0.014	0.056	-9999	-0.14	66	66
PLD2	-0.004	0.071	-9999	-0.22	47	47
G12/G13	0.005	0.08	-9999	-0.24	46	46
PI3K-beta	-0.039	0.098	-9999	-0.36	30	30
cell migration	0.016	0.062	-9999	-0.25	17	17
SLC9A3R2	-0.032	0.15	-9999	-0.49	52	52
PXN	0.001	0.064	-9999	-0.2	45	45
HRAS/GTP	0.001	0.1	-9999	-0.28	49	49
RAC1	0.018	0	-9999	-10000	0	0
MMP9	-0.042	0.17	-9999	-0.51	60	60
PRKCE	0.01	0.061	-9999	-0.43	9	9
PRKCD	-0.019	0.094	-9999	-0.26	56	56
Gi(beta/gamma)	0	0.11	-9999	-0.29	48	48
mol:LPA	-0.012	0.052	-9999	-0.16	54	54
TRIP6/p130 Cas/FAK1/Paxillin	0.012	0.086	-9999	-0.34	13	13
MAPKKK cascade	0.001	0.1	-9999	-0.28	49	49
contractile ring contraction involved in cytokinesis	-0.007	0.092	-9999	-0.4	17	17
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.043	0.096	-9999	-0.25	70	70
GNA15	-0.003	0.051	-9999	-0.18	23	23
GNA12	0.018	0	-9999	-10000	0	0
GNA13	0.011	0.055	-9999	-0.36	10	10
MAPT	-0.047	0.13	-9999	-0.27	116	116
GNA11	0.002	0.038	-9999	-0.3	4	4
Rac1/GTP	0.005	0.16	-9999	-0.94	15	15
MMP2	-0.036	0.18	-9999	-0.55	54	54

×

BCR 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
JUN	-0.061	0.16	-10000	0	-0.39	72	72
IKBKB	0.005	0.077	-10000	0	-0.25	11	11
AKT1	-0.017	0.098	0.21	10	-0.22	49	59
IKBKG	0.008	0.078	-10000	0	-0.25	11	11
CALM1	-0.03	0.13	0.21	11	-0.35	48	59
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
MAP3K1	-0.075	0.19	-10000	0	-0.47	69	69
MAP3K7	0.016	0.02	-10000	0	-0.25	3	3
mol:Ca2+	-0.039	0.14	0.21	11	-0.35	57	68
DOK1	0.002	0.083	-10000	0	-0.41	19	19
AP-1	-0.045	0.1	0.18	1	-0.24	73	74
LYN	0.014	0.031	-10000	0	-0.25	7	7
BLNK	-0.012	0.12	-10000	0	-0.51	30	30
SHC1	0.017	0.023	-10000	0	-0.52	1	1
BCR complex	-0.033	0.13	-10000	0	-0.34	71	71
CD22	-0.055	0.19	-10000	0	-0.48	63	63
CAMK2G	-0.022	0.12	0.21	11	-0.33	45	56
CSNK2A1	0.017	0.023	-10000	0	-0.52	1	1
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.057	0.11	-10000	0	-0.44	21	21
GO:0007205	-0.04	0.14	0.21	11	-0.36	57	68
SYK	-0.023	0.14	-10000	0	-0.48	43	43
ELK1	-0.032	0.13	0.21	11	-0.36	49	60
NFATC1	-0.04	0.16	-10000	0	-0.38	64	64
B-cell antigen/BCR complex	-0.033	0.13	-10000	0	-0.34	71	71
PAG1/CSK	0.009	0.074	-10000	0	-0.37	16	16
NFKBIB	0.014	0.031	0.097	1	-0.11	3	4
HRAS	-0.028	0.13	0.19	3	-0.33	51	54
NFKBIA	0.015	0.03	0.097	1	-0.13	1	2
NF-kappa-B/RelA/I kappa B beta	0.02	0.027	-10000	0	-0.16	1	1
RasGAP/Csk	-0.026	0.14	-10000	0	-0.31	77	77
mol:GDP	-0.038	0.13	0.21	11	-0.34	57	68
PTEN	-0.002	0.1	-10000	0	-0.52	19	19
CD79B	-0.042	0.15	-10000	0	-0.36	84	84
NF-kappa-B/RelA/I kappa B alpha	0.02	0.027	-10000	0	-0.16	1	1
GRB2	0.016	0.024	-10000	0	-0.25	4	4
PI3K/BCAP/CD19	-0.063	0.18	-10000	0	-0.48	60	60
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
mol:IP3	-0.041	0.14	0.21	11	-0.36	57	68
CSK	0.015	0.031	-10000	0	-0.32	4	4
FOS	-0.078	0.15	0.21	8	-0.32	113	121
CHUK	0.001	0.094	-10000	0	-0.32	21	21
IBTK	0.016	0.033	-10000	0	-0.52	2	2
CARD11/BCL10/MALT1/TAK1	-0.023	0.12	0.2	1	-0.36	39	40
PTPN6	-0.046	0.18	-10000	0	-0.52	48	48
RELA	0.018	0	-10000	0	-10000	0	0
BCL2A1	0.013	0.03	-10000	0	-0.096	9	9
VAV2	-0.065	0.19	-10000	0	-0.51	60	60
ubiquitin-dependent protein catabolic process	0.019	0.03	0.1	1	-0.11	2	3
BTK	-0.036	0.2	-10000	0	-1.1	18	18
CD19	-0.073	0.2	-10000	0	-0.44	90	90
MAP4K1	0.012	0.04	-10000	0	-0.25	12	12
CD72	-0.03	0.14	-10000	0	-0.37	65	65
PAG1	-0.005	0.097	-10000	0	-0.38	30	30
MAPK14	-0.057	0.16	-10000	0	-0.41	63	63
SH3BP5	-0.005	0.1	-10000	0	-0.44	26	26
PIK3AP1	-0.045	0.16	0.23	11	-0.43	54	65
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.055	0.19	-10000	0	-0.44	71	71
RAF1	-0.02	0.12	-10000	0	-0.32	45	45
RasGAP/p62DOK/SHIP	-0.036	0.15	-10000	0	-0.32	79	79
CD79A	-0.011	0.084	-10000	0	-0.26	54	54
re-entry into mitotic cell cycle	-0.045	0.1	0.18	1	-0.24	72	73
RASA1	0.004	0.078	-10000	0	-0.42	16	16
MAPK3	-0.003	0.1	-10000	0	-0.31	28	28
MAPK1	-0.003	0.1	-10000	0	-0.31	29	29
CD72/SHP1	-0.055	0.19	-10000	0	-0.51	60	60
NFKB1	0.017	0.023	-10000	0	-0.52	1	1
MAPK8	-0.058	0.17	-10000	0	-0.42	61	61
actin cytoskeleton organization	-0.049	0.17	-10000	0	-0.44	59	59
NF-kappa-B/RelA	0.043	0.054	0.19	1	-0.23	3	4
Calcineurin	-0.023	0.12	-10000	0	-0.34	43	43
PI3K	-0.087	0.14	-10000	0	-0.39	74	74
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.043	0.15	0.24	11	-0.4	52	63
SOS1	0.017	0.023	-10000	0	-0.52	1	1
Bam32/HPK1	-0.13	0.31	-10000	0	-0.75	95	95
DAPP1	-0.16	0.35	-10000	0	-0.86	95	95
cytokine secretion	-0.037	0.15	-10000	0	-0.35	64	64
mol:DAG	-0.041	0.14	0.21	11	-0.36	57	68
PLCG2	-0.017	0.11	-10000	0	-0.32	55	55
MAP2K1	-0.011	0.11	-10000	0	-0.33	32	32
B-cell antigen/BCR complex/FcgammaRIIB	-0.045	0.15	-10000	0	-0.32	106	106
mol:PI-3-4-5-P3	-0.058	0.11	0.25	13	-0.29	63	76
ETS1	-0.019	0.12	0.2	10	-0.35	39	49
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.031	0.15	-10000	0	-0.31	86	86
B-cell antigen/BCR complex/LYN	-0.077	0.18	-10000	0	-0.51	56	56
MALT1	0.011	0.053	-10000	0	-0.37	9	9
TRAF6	0.017	0.023	-10000	0	-0.52	1	1
RAC1	-0.053	0.18	-10000	0	-0.47	57	57
B-cell antigen/BCR complex/LYN/SYK	-0.053	0.19	-10000	0	-0.51	59	59
CARD11	-0.038	0.14	0.21	11	-0.35	64	75
FCGR2B	-0.031	0.15	-10000	0	-0.5	50	50
PPP3CA	0.006	0.073	-10000	0	-0.44	13	13
BCL10	0.017	0.012	-10000	0	-0.25	1	1
IKK complex	0.012	0.04	0.11	1	-0.11	8	9
PTPRC	-0.04	0.15	-10000	0	-0.41	71	71
PDPK1	-0.017	0.091	0.2	9	-0.21	51	60
PPP3CB	0.016	0.026	-10000	0	-0.39	2	2
PPP3CC	-0.001	0.098	-10000	0	-0.51	19	19
POU2F2	0.019	0.021	-10000	0	-0.098	1	1

×

Caspase cascade in apoptosis

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
TOP1	-0.002	0.11	0.22	4	-0.26	52	56
ACTA1	-0.03	0.14	0.24	8	-0.33	64	72
NUMA1	-0.005	0.11	0.22	3	-0.26	54	57
SPTAN1	-0.01	0.13	0.24	11	-0.32	55	66
LIMK1	-0.029	0.15	0.23	9	-0.33	78	87
BIRC3	-0.085	0.19	-10000	0	-0.41	128	128
BIRC2	0.016	0.02	-10000	0	-0.25	3	3
BAX	0.016	0.02	-10000	0	-0.25	3	3
CASP10	-0.042	0.13	-10000	0	-0.31	100	100
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	-0.003	0.12	0.22	3	-0.27	52	55
DIABLO	0.018	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.009	0.13	0.23	11	-0.32	55	66
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.01	0.063	-10000	0	-0.49	8	8
GSN	-0.019	0.14	0.23	9	-0.33	65	74
MADD	0.018	0	-10000	0	-10000	0	0
TFAP2A	-0.009	0.14	-10000	0	-0.56	27	27
BID	-0.022	0.089	-10000	0	-0.2	96	96
MAP3K1	-0.029	0.13	-10000	0	-0.41	43	43
TRADD	0.016	0.026	-10000	0	-0.39	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.022	0.041	-10000	0	-0.37	5	5
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.029	0.14	0.23	5	-0.33	69	74
CASP9	0.017	0.023	-10000	0	-0.52	1	1
DNA repair	-0.02	0.075	0.29	8	-0.19	37	45
neuron apoptosis	-0.026	0.17	-10000	0	-0.64	36	36
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.005	0.13	0.23	11	-0.3	56	67
APAF1	0.012	0.051	-10000	0	-0.41	7	7
CASP6	0.003	0.11	-10000	0	-0.7	7	7
TRAF2	0.014	0.042	-10000	0	-0.45	4	4
ICAD/CAD	-0.003	0.13	0.23	11	-0.31	55	66
CASP7	0.044	0.12	0.29	68	-0.4	11	79
KRT18	-0.071	0.21	-10000	0	-0.57	76	76
apoptosis	-0.005	0.13	0.26	8	-0.3	56	64
DFFA	-0.01	0.13	0.24	11	-0.32	55	66
DFFB	-0.01	0.13	0.24	11	-0.32	55	66
PARP1	0.02	0.075	0.19	37	-0.3	8	45
actin filament polymerization	0.026	0.14	0.3	85	-0.22	9	94
TNF	-0.004	0.094	-10000	0	-0.36	31	31
CYCS	-0.012	0.062	-10000	0	-0.16	34	34
SATB1	-0.019	0.13	-10000	0	-0.46	23	23
SLK	-0.01	0.13	0.24	11	-0.32	56	67
p15 BID/BAX	-0.011	0.081	-10000	0	-0.28	11	11
CASP2	0.011	0.089	-10000	0	-0.38	11	11
JNK cascade	0.029	0.13	0.41	43	-10000	0	43
CASP3	-0.017	0.14	0.24	14	-0.34	61	75
LMNB2	0.018	0.068	-10000	0	-0.29	7	7
RIPK1	0.017	0.023	-10000	0	-0.52	1	1
CASP4	-0.005	0.11	-10000	0	-0.49	24	24
Mammalian IAPs/DIABLO	-0.024	0.11	-10000	0	-0.28	76	76
negative regulation of DNA binding	-0.009	0.14	-10000	0	-0.56	27	27
stress fiber formation	-0.01	0.13	0.23	11	-0.32	56	67
GZMB	-0.058	0.16	-10000	0	-0.37	98	98
CASP1	-0.038	0.16	-10000	0	-0.42	60	60
LMNB1	-0.032	0.12	-10000	0	-0.29	38	38
APP	-0.027	0.17	-10000	0	-0.65	36	36
TNFRSF1A	0.016	0.033	-10000	0	-0.52	2	2
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.013	0	-10000	0	-10000	0	0
VIM	-0.009	0.13	0.26	8	-0.3	56	64
LMNA	0.014	0.076	-10000	0	-0.3	11	11
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.004	0.094	-10000	0	-0.38	13	13
LRDD	0.018	0	-10000	0	-10000	0	0
SREBF1	-0.036	0.15	0.24	10	-0.32	86	96
APAF-1/Caspase 9	0.014	0.068	-10000	0	-0.57	2	2
nuclear fragmentation during apoptosis	-0.005	0.11	0.22	3	-0.25	54	57
CFL2	-0.027	0.15	0.22	9	-0.31	85	94
GAS2	-0.035	0.15	0.24	10	-0.32	83	93
positive regulation of apoptosis	-0.002	0.08	-10000	0	-0.26	21	21
PRF1	-0.008	0.091	-10000	0	-0.3	43	43

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.042	0.15	-9999	-0.38	76	76
EPHB2	0.007	0.061	-9999	-0.32	16	16
Syndecan-2/TACI	-0.006	0.092	-9999	-0.3	38	38
LAMA1	0.015	0.026	-9999	-0.25	5	5
Syndecan-2/alpha2 ITGB1	-0.062	0.17	-9999	-0.31	139	139
HRAS	0.012	0.051	-9999	-0.41	7	7
Syndecan-2/CASK	-0.016	0.089	-9999	-0.31	38	38
ITGA5	0.015	0.035	-9999	-0.43	3	3
BAX	0.01	0.085	-9999	-10000	0	0
EPB41	0.016	0.026	-9999	-0.39	2	2
positive regulation of cell-cell adhesion	-0.011	0.094	-9999	-0.28	49	49
LAMA3	-0.07	0.19	-9999	-0.43	103	103
EZR	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.019	0.12	-9999	-0.39	48	48
Syndecan-2/MMP2	-0.033	0.14	-9999	-0.38	65	65
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.024	0.13	-9999	-0.37	58	58
dendrite morphogenesis	-0.009	0.095	-9999	-0.3	42	42
Syndecan-2/GM-CSF	-0.014	0.099	-9999	-0.31	43	43
determination of left/right symmetry	-0.017	0.11	-9999	-0.37	38	38
Syndecan-2/PKC delta	-0.006	0.094	-9999	-0.3	41	41
GNB2L1	0.015	0.04	-9999	-0.52	3	3
MAPK3	-0.005	0.09	-9999	-0.27	44	44
MAPK1	-0.005	0.092	-9999	-0.28	44	44
Syndecan-2/RACK1	0.004	0.087	-9999	-0.26	44	44
NF1	0.015	0.035	-9999	-0.43	3	3
FGFR/FGF/Syndecan-2	-0.017	0.11	-9999	-0.37	38	38
ITGA2	-0.048	0.17	-9999	-0.46	73	73
MAPK8	0.001	0.094	-9999	-0.3	41	41
Syndecan-2/alpha2/beta1 Integrin	-0.018	0.13	-9999	-0.3	84	84
Syndecan-2/Kininogen	-0.004	0.091	-9999	-0.3	38	38
ITGB1	0.014	0.044	-9999	-0.41	5	5
SRC	0.007	0.085	-9999	-0.25	45	45
Syndecan-2/CASK/Protein 4.1	-0.004	0.083	-9999	-0.27	39	39
extracellular matrix organization	-0.004	0.091	-9999	-0.3	39	39
actin cytoskeleton reorganization	-0.042	0.15	-9999	-0.38	76	76
Syndecan-2/Caveolin-2/Ras	-0.014	0.12	-9999	-0.33	55	55
Syndecan-2/Laminin alpha3	-0.055	0.15	-9999	-0.34	99	99
Syndecan-2/RasGAP	0.006	0.094	-9999	-0.25	52	52
alpha5/beta1 Integrin	0.022	0.041	-9999	-0.37	5	5
PRKCD	0.014	0.042	-9999	-0.45	4	4
Syndecan-2 dimer	-0.009	0.096	-9999	-0.3	42	42
GO:0007205	0.004	0.005	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.012	0.094	-9999	-0.24	53	53
RHOA	0.005	0.08	-9999	-0.52	12	12
SDCBP	0.003	0.081	-9999	-0.4	19	19
TNFRSF13B	0.013	0.035	-9999	-0.25	9	9
RASA1	0.004	0.078	-9999	-0.42	16	16
alpha2/beta1 Integrin	-0.024	0.13	-9999	-0.37	58	58
Syndecan-2/Synbindin	-0.003	0.091	-9999	-0.3	38	38
TGFB1	0.017	0.023	-9999	-0.52	1	1
CASP3	0.003	0.085	-9999	-0.27	41	41
FN1	-0.048	0.17	-9999	-0.46	73	73
Syndecan-2/IL8	-0.055	0.14	-9999	-0.33	87	87
SDC2	-0.017	0.11	-9999	-0.37	38	38
KNG1	0.017	0.017	-9999	-0.25	2	2
Syndecan-2/Neurofibromin	-0.005	0.093	-9999	-0.3	40	40
TRAPPC4	0.018	0	-9999	-10000	0	0
CSF2	-0.001	0.074	-9999	-0.28	33	33
Syndecan-2/TGFB1	-0.004	0.092	-9999	-0.3	39	39
Syndecan-2/Syntenin/PI-4-5-P2	-0.011	0.094	-9999	-0.28	49	49
Syndecan-2/Ezrin	-0.01	0.092	-9999	-0.28	50	50
PRKACA	0.004	0.084	-9999	-0.27	40	40
angiogenesis	-0.055	0.14	-9999	-0.33	87	87
MMP2	-0.032	0.15	-9999	-0.47	54	54
IL8	-0.072	0.17	-9999	-0.34	135	135
calcineurin-NFAT signaling pathway	-0.006	0.092	-9999	-0.3	38	38

×

TCGA08_p53

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
CDKN2A	-0.037	0.11	-10000	0	-0.23	108	108
TP53	-0.036	0.1	0.28	2	-0.36	37	39
Senescence	-0.036	0.1	0.28	2	-0.36	37	39
Apoptosis	-0.036	0.1	0.28	2	-0.36	37	39
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.028	0.072	0.24	31	-0.18	13	44
MDM4	0.013	0.044	-10000	0	-0.32	8	8

×

Signaling events mediated by PTP1B

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
PDGFRB	0.01	0.066	-10000	0	-0.52	8	8
Jak2/Leptin Receptor	-0.039	0.12	0.21	1	-0.34	49	50
PTP1B/AKT1	-0.043	0.12	0.29	2	-0.33	45	47
FYN	0.008	0.067	-10000	0	-0.41	12	12
p210 bcr-abl/PTP1B	-0.055	0.12	0.32	2	-0.32	63	65
EGFR	-0.085	0.18	-10000	0	-0.36	139	139
EGF/EGFR	-0.14	0.2	-10000	0	-0.38	184	184
CSF1	0.014	0.037	-10000	0	-0.29	7	7
AKT1	0.011	0.054	-10000	0	-0.38	9	9
INSR	0.015	0.037	-10000	0	-0.39	4	4
PTP1B/N-cadherin	-0.065	0.15	0.28	2	-0.35	72	74
Insulin Receptor/Insulin	-0.02	0.1	-10000	0	-0.34	23	23
HCK	-0.005	0.11	-10000	0	-0.47	25	25
CRK	0.016	0.033	-10000	0	-0.52	2	2
TYK2	-0.046	0.12	0.3	2	-0.32	55	57
EGF	-0.15	0.23	-10000	0	-0.43	193	193
YES1	0.007	0.07	-10000	0	-0.43	12	12
CAV1	-0.074	0.14	0.29	2	-0.37	62	64
TXN	0.013	0.017	-10000	0	-0.26	2	2
PTP1B/IRS1/GRB2	-0.067	0.15	-10000	0	-0.35	89	89
cell migration	0.055	0.12	0.32	63	-0.32	2	65
STAT3	0.014	0.041	-10000	0	-0.52	3	3
PRLR	-0.027	0.15	-10000	0	-0.49	50	50
ITGA2B	0.015	0.02	-10000	0	-0.25	3	3
CSF1R	0.017	0.017	-10000	0	-0.25	2	2
Prolactin Receptor/Prolactin	-0.002	0.12	-10000	0	-0.36	47	47
FGR	0.017	0.017	-10000	0	-0.25	2	2
PTP1B/p130 Cas	-0.044	0.12	0.28	2	-0.32	55	57
Crk/p130 Cas	-0.036	0.12	-10000	0	-0.33	42	42
DOK1	-0.039	0.13	0.3	2	-0.38	40	42
JAK2	-0.037	0.12	-10000	0	-0.35	41	41
Jak2/Leptin Receptor/Leptin	-0.069	0.13	-10000	0	-0.36	53	53
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
PTPN1	-0.056	0.12	0.32	2	-0.33	63	65
LYN	0.014	0.031	-10000	0	-0.25	7	7
CDH2	-0.027	0.13	-10000	0	-0.34	66	66
SRC	-0.005	0.07	-10000	0	-0.68	3	3
ITGB3	0.001	0.076	-10000	0	-0.32	25	25
CAT1/PTP1B	-0.085	0.17	0.27	1	-0.44	65	66
CAPN1	0.003	0.078	-10000	0	-0.44	15	15
CSK	0.015	0.031	-10000	0	-0.32	4	4
PI3K	-0.036	0.1	-10000	0	-0.35	30	30
mol:H2O2	-0.003	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.062	0.12	-10000	0	-0.38	40	40
negative regulation of transcription	-0.037	0.11	-10000	0	-0.35	41	41
FCGR2A	-0.003	0.099	-10000	0	-0.45	23	23
FER	0.013	0.027	-10000	0	-0.4	2	2
alphaIIb/beta3 Integrin	0.011	0.056	-10000	0	-0.37	7	7
BLK	-0.019	0.1	-10000	0	-0.29	63	63
Insulin Receptor/Insulin/Shc	0.032	0.032	-10000	0	-0.31	4	4
RHOA	0.004	0.081	-10000	0	-0.53	12	12
LEPR	-0.005	0.093	-10000	0	-0.34	34	34
BCAR1	0.017	0.012	-10000	0	-0.25	1	1
p210 bcr-abl/Grb2	0.016	0.023	-10000	0	-0.25	4	4
mol:NADPH	-0.003	0.004	-10000	0	-10000	0	0
TRPV6	-0.06	0.16	-10000	0	-0.44	54	54
PRL	0.018	0.033	-10000	0	-0.32	4	4
SOCS3	-0.005	0.17	-10000	0	-1.3	8	8
SPRY2	-0.036	0.15	-10000	0	-0.43	60	60
Insulin Receptor/Insulin/IRS1	-0.008	0.12	-10000	0	-0.32	62	62
CSF1/CSF1R	-0.037	0.12	-10000	0	-0.34	39	39
Ras protein signal transduction	0.029	0.039	-10000	0	-0.19	3	3
IRS1	-0.048	0.17	-10000	0	-0.49	68	68
INS	0.017	0.024	-10000	0	-0.53	1	1
LEP	-0.051	0.15	-10000	0	-0.34	101	101
STAT5B	-0.043	0.11	0.25	2	-0.28	64	66
STAT5A	-0.044	0.11	0.25	2	-0.28	65	67
GRB2	0.016	0.024	-10000	0	-0.25	4	4
PDGFB-D/PDGFRB	-0.048	0.13	0.28	2	-0.36	55	57
CSN2	0.02	0.1	-10000	0	-1.4	2	2
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
LAT	-0.025	0.12	-10000	0	-0.55	19	19
YBX1	0.007	0.072	-10000	0	-0.33	16	16
LCK	-0.074	0.18	-10000	0	-0.4	117	117
SHC1	0.017	0.023	-10000	0	-0.52	1	1
NOX4	-0.059	0.18	-10000	0	-0.49	78	78

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.01	0.064	-9999	-0.37	9	9
alphaV beta3 Integrin	-0.034	0.13	-9999	-0.33	62	62
PTK2	-0.008	0.14	-9999	-0.48	25	25
IGF1R	-0.083	0.2	-9999	-0.47	110	110
PI4KB	0.016	0.033	-9999	-0.52	2	2
MFGE8	-0.018	0.12	-9999	-0.36	50	50
SRC	0.015	0.035	-9999	-0.43	3	3
CDKN1B	-0.022	0.13	-9999	-0.48	30	30
VEGFA	0	0.075	-9999	-0.29	31	31
ILK	0.002	0.072	-9999	-0.75	2	2
ROCK1	0.018	0	-9999	-10000	0	0
AKT1	0.007	0.075	-9999	-0.49	5	5
PTK2B	0.012	0.091	-9999	-0.32	27	27
alphaV/beta3 Integrin/JAM-A	-0.014	0.12	-9999	-0.28	60	60
CBL	0.017	0.012	-9999	-0.25	1	1
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.01	0.087	-9999	-0.33	27	27
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.11	0.22	-9999	-0.39	169	169
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.021	0.086	-9999	-0.37	14	14
alphaV/beta3 Integrin/Syndecan-1	-0.02	0.13	-9999	-0.33	67	67
PI4KA	0.018	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.18	0.24	-9999	-0.53	131	131
PI4 Kinase	0.025	0.024	-9999	-0.37	2	2
PIK3CA	0.016	0.029	-9999	-0.34	3	3
alphaV/beta3 Integrin/Osteopontin	-0.082	0.16	-9999	-0.33	141	141
RPS6KB1	-0.15	0.23	-9999	-0.49	135	135
TLN1	0.017	0.023	-9999	-0.52	1	1
MAPK3	-0.092	0.22	-9999	-0.65	57	57
GPR124	0	0.095	-9999	-0.52	17	17
MAPK1	-0.092	0.22	-9999	-0.65	57	57
PXN	0.018	0	-9999	-10000	0	0
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
alphaV/beta3 Integrin/Tumstatin	0.011	0.087	-9999	-0.35	24	24
cell adhesion	-0.008	0.12	-9999	-0.42	24	24
ANGPTL3	0.011	0.056	-9999	-0.42	8	8
VEGFR2 homodimer/VEGFA homodimer/Src	0.021	0.059	-9999	-0.3	11	11
IGF-1R heterotetramer	-0.083	0.2	-9999	-0.47	110	110
Rac1/GDP	0.013	0	-9999	-10000	0	0
TGFBR2	0.013	0.049	-9999	-0.43	6	6
ITGB3	0.002	0.075	-9999	-0.32	25	25
IGF1	-0.1	0.2	-9999	-0.41	146	146
RAC1	0.018	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	0.004	0.11	-9999	-0.38	33	33
apoptosis	-0.002	0.099	-9999	-0.48	21	21
CD47	-0.005	0.11	-9999	-0.47	25	25
alphaV/beta3 Integrin/CD47	0	0.1	-9999	-0.32	42	42
VCL	0.016	0.029	-9999	-0.34	3	3
alphaV/beta3 Integrin/Del1	-0.066	0.17	-9999	-0.35	115	115
CSF1	0.014	0.037	-9999	-0.29	7	7
PIK3C2A	-0.003	0.096	-9999	-0.74	6	6
PI4 Kinase/Pyk2	-0.042	0.092	-9999	-0.4	18	18
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.013	0.099	-9999	-0.34	29	29
FAK1/Vinculin	0.004	0.11	-9999	-0.38	24	24
alphaV beta3/Integrin/ppsTEM5	0.004	0.11	-9999	-0.38	33	33
RHOA	0.005	0.08	-9999	-0.52	12	12
VTN	0.016	0.02	-9999	-0.25	3	3
BCAR1	0.017	0.012	-9999	-0.25	1	1
FGF2	-0.064	0.16	-9999	-0.34	122	122
F11R	-0.037	0.12	-9999	-0.37	41	41
alphaV/beta3 Integrin/Lactadherin	-0.006	0.12	-9999	-0.39	38	38
alphaV/beta3 Integrin/TGFBR2	0.011	0.089	-9999	-0.35	26	26
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.031	0.062	-9999	-0.27	19	19
HSP90AA1	0.013	0.045	-9999	-0.39	6	6
alphaV/beta3 Integrin/Talin	0.014	0.075	-9999	-0.31	23	23
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.048	0.17	-9999	-0.46	73	73
alphaV/beta3 Integrin/Pyk2	0.018	0.094	-9999	-0.32	27	27
SDC1	-0.038	0.16	-9999	-0.46	62	62
VAV3	-0.024	0.13	-9999	-0.27	102	102
PTPN11	0.017	0.023	-9999	-0.52	1	1
IRS1	-0.048	0.17	-9999	-0.49	68	68
FAK1/Paxillin	0.004	0.11	-9999	-0.38	22	22
cell migration	0.011	0.1	-9999	-0.38	15	15
ITGAV	-0.002	0.1	-9999	-0.48	21	21
PI3K	-0.016	0.12	-9999	-0.41	22	22
SPP1	-0.14	0.23	-9999	-0.43	188	188
KDR	0.013	0.052	-9999	-0.52	5	5
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	-0.002	0.099	-9999	-0.48	21	21
COL4A3	0.013	0.047	-9999	-0.37	7	7
angiogenesis	-0.081	0.22	-9999	-0.65	56	56
Rac1/GTP	-0.013	0.12	-9999	-0.42	11	11
EDIL3	-0.11	0.22	-9999	-0.44	152	152
cell proliferation	0.011	0.089	-9999	-0.34	26	26

×

Canonical Wnt signaling pathway

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
HDAC1	0.035	0.05	0.21	4	-0.53	1	5
AES	0.033	0.037	0.2	3	-10000	0	3
FBXW11	0.015	0.035	-10000	0	-0.43	3	3
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.009	0.076	-10000	0	-0.36	19	19
SMAD4	0.009	0.067	-10000	0	-0.49	9	9
DKK2	-0.026	0.14	-10000	0	-0.42	52	52
TLE1	-0.017	0.16	0.2	2	-0.45	55	57
MACF1	0.016	0.026	-10000	0	-0.39	2	2
CTNNB1	-0.006	0.098	0.28	2	-0.35	15	17
WIF1	-0.024	0.098	-10000	0	-0.25	81	81
beta catenin/RanBP3	0.069	0.19	0.38	114	-0.46	2	116
KREMEN2	-0.19	0.23	-10000	0	-0.41	257	257
DKK1	-0.12	0.19	-10000	0	-0.34	199	199
beta catenin/beta TrCP1	0.005	0.096	0.27	2	-0.35	13	15
FZD1	0.003	0.082	-10000	0	-0.43	17	17
AXIN2	-0.097	0.33	-10000	0	-1.3	31	31
AXIN1	0.017	0.012	-10000	0	-0.25	1	1
RAN	0.018	0.012	-10000	0	-0.25	1	1
Axin1/APC/GSK3/beta catenin	0.034	0.036	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.017	0.16	-10000	0	-0.43	35	35
Axin1/APC/GSK3	0.049	0.042	0.24	4	-10000	0	4
Axin1/APC/GSK3/beta catenin/Macf1	0.037	0.067	-10000	0	-0.3	2	2
HNF1A	0.031	0.044	0.2	1	-0.24	3	4
CTBP1	0.033	0.041	0.21	2	-0.26	1	3
MYC	-0.12	0.36	-10000	0	-1.2	44	44
RANBP3	0.018	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.12	0.16	-10000	0	-0.33	186	186
NKD1	0.009	0.059	-10000	0	-0.38	11	11
TCF4	0.008	0.12	0.2	2	-0.49	26	28
TCF3	0.029	0.057	0.18	9	-0.29	8	17
WNT1/LRP6/FZD1/Axin1	0.031	0.062	-10000	0	-0.27	20	20
Ran/GTP	0.014	0.009	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.098	0.25	0.5	120	-0.48	8	128
LEF1	-0.007	0.13	0.2	4	-0.31	64	68
DVL1	0.045	0.042	-10000	0	-0.31	3	3
CSNK2A1	0.017	0.023	-10000	0	-0.52	1	1
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.038	0.17	-10000	0	-0.49	35	35
DKK1/LRP6/Kremen 2	-0.17	0.17	-10000	0	-0.33	249	249
LRP6	0.008	0.065	-10000	0	-0.38	13	13
CSNK1A1	0.035	0.048	0.19	17	-0.46	1	18
NLK	0.008	0.044	-10000	0	-0.28	11	11
CCND1	-0.25	0.54	-10000	0	-1.4	87	87
WNT1	0.016	0.023	-10000	0	-0.52	1	1
GSK3A	0.018	0.001	-10000	0	-10000	0	0
GSK3B	0.017	0.001	-10000	0	-10000	0	0
FRAT1	0.008	0.068	-10000	0	-0.47	10	10
PPP2R5D	0.028	0.035	0.26	5	-10000	0	5
APC	0.026	0.062	-10000	0	-0.24	23	23
WNT1/LRP6/FZD1	0.037	0.06	-10000	0	-0.23	11	11
CREBBP	0.032	0.051	0.21	2	-0.52	2	4

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.002	0.077	-9999	-0.3	26	26
NFATC2	0.013	0.043	-9999	-0.3	5	5
NFATC3	0.015	0.03	-9999	-10000	0	0
CD40LG	-0.097	0.25	-9999	-0.55	86	86
PTGS2	-0.11	0.26	-9999	-0.55	93	93
JUNB	0.011	0.055	-9999	-0.36	10	10
CaM/Ca2+/Calcineurin A alpha-beta B1	0.008	0.018	-9999	-10000	0	0
CaM/Ca2+	0.008	0.018	-9999	-10000	0	0
CALM1	0.016	0.009	-9999	-10000	0	0
JUN	-0.035	0.15	-9999	-0.46	57	57
mol:Ca2+	-0.004	0.011	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.011	0.011	-9999	-0.14	2	2
FOSL1	0.016	0.024	-9999	-0.25	4	4
CREM	0.016	0.017	-9999	-0.26	2	2
Jun/NFAT1-c-4/p21SNFT	-0.024	0.15	-9999	-0.35	53	53
FOS	-0.11	0.2	-9999	-0.37	171	171
IFNG	-0.14	0.3	-9999	-0.6	115	115
AP-1/NFAT1-c-4	-0.1	0.3	-9999	-0.62	95	95
FASLG	-0.12	0.3	-9999	-0.61	110	110
NFAT1-c-4/ICER1	0.008	0.095	-9999	-0.31	14	14
IL2RA	-0.11	0.28	-9999	-0.56	106	106
FKBP12/FK506	0.012	0.011	-9999	-0.17	2	2
CSF2	-0.099	0.26	-9999	-0.55	90	90
JunB/Fra1/NFAT1-c-4	0.016	0.1	-9999	-0.33	14	14
IL4	-0.095	0.25	-9999	-0.54	86	86
IL2	-0.005	0.1	-9999	-1.3	3	3
IL3	0.008	0.021	-9999	-10000	0	0
FKBP1A	0.017	0.017	-9999	-0.25	2	2
BATF3	0	0	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.026	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.002	0.07	-9999	-0.28	28	28
Caspase 8 (4 units)	-0.034	0.14	-9999	-0.39	37	37
NEF	-0.014	0.042	-9999	-0.18	10	10
NFKBIA	-0.004	0.061	-9999	-0.52	4	4
BIRC3	-0.064	0.21	-9999	-0.55	74	74
CYCS	-0.04	0.14	-9999	-0.4	38	38
RIPK1	0.017	0.023	-9999	-0.52	1	1
CD247	-0.13	0.24	-9999	-0.47	153	153
MAP2K7	-0.023	0.13	-9999	-0.53	14	14
protein ubiquitination	0.018	0.095	-9999	-0.34	12	12
CRADD	0.01	0.063	-9999	-0.49	8	8
DAXX	0.017	0.012	-9999	-0.25	1	1
FAS	-0.024	0.13	-9999	-0.42	51	51
BID	-0.048	0.14	-9999	-0.33	77	77
NF-kappa-B/RelA/I kappa B alpha	-0.014	0.12	-9999	-0.27	76	76
TRADD	0.016	0.026	-9999	-0.39	2	2
MAP3K5	-0.022	0.13	-9999	-0.42	47	47
CFLAR	0.009	0.065	-9999	-0.44	10	10
FADD	0	0.067	-9999	-0.25	35	35
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.014	0.12	-9999	-0.27	76	76
MAPK8	-0.016	0.12	-9999	-0.55	11	11
APAF1	0.012	0.051	-9999	-0.41	7	7
TRAF1	0.013	0.04	-9999	-0.28	9	9
TRAF2	0.014	0.042	-9999	-0.45	4	4
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.052	0.15	-9999	-0.32	91	91
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.01	0.1	-9999	-0.43	9	9
CHUK	0.017	0.1	-9999	-0.37	12	12
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0	0.11	-9999	-0.29	55	55
TCRz/NEF	-0.11	0.21	-9999	-0.43	133	133
TNF	-0.004	0.094	-9999	-0.36	31	31
FASLG	-0.12	0.26	-9999	-0.46	157	157
NFKB1	-0.001	0.046	-9999	-0.52	1	1
TNFR1A/BAG4/TNF-alpha	0.012	0.074	-9999	-0.31	18	18
CASP6	-0.02	0.14	-9999	-0.55	18	18
CASP7	-0.072	0.23	-9999	-0.54	80	80
RELA	0	0.04	-9999	-10000	0	0
CASP2	0.018	0	-9999	-10000	0	0
CASP3	-0.066	0.22	-9999	-0.54	78	78
TNFRSF1A	0.016	0.033	-9999	-0.52	2	2
TNFR1A/BAG4	0.014	0.054	-9999	-0.37	5	5
CASP8	0.018	0	-9999	-10000	0	0
CASP9	0.017	0.023	-9999	-0.52	1	1
MAP3K14	0.015	0.1	-9999	-0.43	9	9
APAF-1/Caspase 9	-0.097	0.15	-9999	-0.4	87	87
BCL2	-0.066	0.15	-9999	-0.44	35	35

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.011	0.056	-9999	-0.42	8	8
GNAT1/GTP	0.01	0.035	-9999	-0.34	5	5
Metarhodopsin II/Arrestin	-0.045	0.12	-9999	-0.31	64	64
PDE6G/GNAT1/GTP	0.02	0.033	-9999	-0.31	4	4
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.013	0.048	-9999	-0.47	5	5
GRK1	0	0	-9999	-10000	0	0
CNG Channel	-0.082	0.12	-9999	-0.36	46	46
mol:Na +	-0.04	0.088	-9999	-0.43	14	14
mol:ADP	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.056	0.15	-9999	-0.34	96	96
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.002	0.11	-9999	-0.44	14	14
CNGB1	0.018	0	-9999	-10000	0	0
RDH5	-0.003	0.072	-9999	-0.25	40	40
SAG	-0.098	0.19	-9999	-0.36	162	162
mol:Ca2+	0.001	0.11	-9999	-0.39	17	17
Na + (4 Units)	-0.039	0.085	-9999	-0.38	17	17
RGS9	-0.033	0.13	-9999	-0.31	81	81
GNB1/GNGT1	-0.033	0.1	-9999	-0.37	18	18
GNAT1/GDP	-0.04	0.13	-9999	-0.29	99	99
GUCY2D	0.018	0	-9999	-10000	0	0
GNGT1	-0.063	0.14	-9999	-0.28	144	144
GUCY2F	0.006	0.076	-9999	-0.46	13	13
GNB5	0.005	0.081	-9999	-0.5	13	13
mol:GMP (4 units)	-0.034	0.12	-9999	-0.26	118	118
mol:11-cis-retinal	-0.003	0.072	-9999	-0.25	40	40
mol:cGMP	0.026	0.087	-9999	-0.3	30	30
GNB1	0.013	0.052	-9999	-0.52	5	5
Rhodopsin	0.012	0.049	-9999	-10000	0	0
SLC24A1	0.011	0.056	-9999	-0.42	8	8
CNGA1	-0.061	0.15	-9999	-0.32	123	123
Metarhodopsin II	0.011	0	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.027	0.075	-9999	-0.29	24	24
RGS9BP	-0.072	0.18	-9999	-0.41	111	111
Metarhodopsin II/Transducin	-0.005	0.064	-9999	-0.25	22	22
GCAP Family/Ca ++	0.016	0.074	-9999	-0.3	24	24
PDE6A/B	-0.066	0.17	-9999	-0.37	115	115
mol:Pi	-0.056	0.15	-9999	-0.34	96	96
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.014	0.083	-9999	-0.29	22	22
PDE6B	-0.1	0.22	-9999	-0.5	123	123
PDE6A	0.011	0.048	-9999	-0.3	11	11
PDE6G	0.016	0.024	-9999	-0.25	4	4
RHO	0.018	0	-9999	-10000	0	0
PDE6	-0.088	0.17	-9999	-0.41	63	63
GUCA1A	0.001	0.092	-9999	-0.48	18	18
GC2/GCAP Family	0.02	0.092	-9999	-0.32	30	30
GUCA1C	0.005	0.078	-9999	-0.43	15	15
GUCA1B	0.014	0.035	-9999	-0.3	6	6

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.034	0.14	-9999	-0.33	76	76
MAP3K8	-0.038	0.15	-9999	-0.39	70	70
FOS	-0.014	0.092	-9999	-0.28	16	16
PRKCA	0.01	0.034	-9999	-0.26	8	8
PTPN7	0.006	0.049	-9999	-0.28	14	14
HRAS	0.011	0.051	-9999	-0.41	7	7
PRKCB	-0.003	0.007	-9999	-0.013	171	171
NRAS	0.004	0.076	-9999	-0.41	16	16
RAS family/GTP	0.013	0.064	-9999	-0.28	20	20
MAPK3	0.002	0.057	-9999	-0.45	2	2
MAP2K1	-0.005	0.064	-9999	-0.22	16	16
ELK1	0.01	0.038	-9999	-0.39	4	4
BRAF	0.004	0.057	-9999	-0.41	7	7
mol:GTP	-0.001	0.002	-9999	-0.004	171	171
MAPK1	0.001	0.06	-9999	-0.43	3	3
RAF1	0.011	0.028	-9999	-10000	0	0
KRAS	0.008	0.065	-9999	-0.44	10	10

×

IL1-mediated signaling events

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
UBC13/UEV1A	0.012	0.011	-9999	-0.17	2	2
PRKCZ	0	0	-9999	-10000	0	0
MAP3K7IP2	0.014	0.047	-9999	-0.52	4	4
ERC1	0.011	0.056	-9999	-0.42	8	8
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.024	0.11	-9999	-0.32	40	40
IRAK/TOLLIP	0.029	0.019	-9999	-0.23	1	1
IKBKB	0.012	0.047	-9999	-0.31	10	10
IKBKG	0.018	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.025	0.12	-9999	-0.36	46	46
IL1A	0.006	0.063	-9999	-0.31	18	18
IL1B	-0.067	0.18	-9999	-0.43	86	86
IRAK/TRAF6/p62/Atypical PKCs	0.031	0.053	-9999	-0.23	18	18
IL1R2	-0.045	0.15	-9999	-0.35	89	89
IL1R1	-0.046	0.16	-9999	-0.4	80	80
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.018	0.12	-9999	-0.29	61	61
TOLLIP	0.017	0.012	-9999	-0.25	1	1
TICAM2	0	0	-9999	-10000	0	0
MAP3K3	0.017	0.012	-9999	-0.25	1	1
TAK1/TAB1/TAB2	0.033	0.034	-9999	-0.34	4	4
IKK complex/ELKS	0.051	0.075	-9999	-0.45	3	3
JUN	0.014	0.093	-9999	-0.44	4	4
MAP3K7	0.016	0.02	-9999	-0.25	3	3
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.059	0.18	-9999	-0.34	120	120
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.002	0.1	-9999	-0.28	57	57
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.005	0.1	-9999	-0.26	57	57
IL1 beta fragment/IL1R1/IL1RAP	-0.069	0.18	-9999	-0.36	120	120
NFKB1	0.017	0.023	-9999	-0.52	1	1
MAPK8	0.032	0.063	-9999	-0.37	2	2
IRAK1	0.019	0.018	-9999	-10000	0	0
IL1RN/IL1R1	-0.061	0.17	-9999	-0.41	87	87
IRAK4	0.014	0.044	-9999	-0.41	5	5
PRKCI	0.002	0.085	-9999	-0.43	18	18
TRAF6	0.017	0.023	-9999	-0.52	1	1
PI3K	0.005	0.082	-9999	-0.37	21	21
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.032	0.13	-9999	-0.36	47	47
CHUK	0.005	0.081	-9999	-0.5	13	13
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.069	0.18	-9999	-0.36	120	120
IL1 beta/IL1R2	-0.082	0.18	-9999	-0.36	128	128
IRAK/TRAF6/TAK1/TAB1/TAB2	0.048	0.033	-9999	-0.33	1	1
NF kappa B1 p50/RelA	-0.082	0.14	-9999	-0.44	54	54
IRAK3	-0.018	0.099	-9999	-0.28	64	64
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.056	0.17	-9999	-0.34	110	110
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.004	0.089	-9999	-0.23	57	57
IL1 alpha/IL1R1/IL1RAP	-0.013	0.11	-9999	-0.31	53	53
RELA	0.018	0	-9999	-10000	0	0
MAP3K7IP1	0.018	0	-9999	-10000	0	0
SQSTM1	0.012	0.053	-9999	-0.48	6	6
MYD88	0.013	0.048	-9999	-0.47	5	5
IRAK/TRAF6/MEKK3	0.038	0.021	-9999	-0.25	1	1
IL1RAP	0.012	0.044	-9999	-0.28	11	11
UBE2N	0.017	0.017	-9999	-0.25	2	2
IRAK/TRAF6	-0.069	0.12	-9999	-0.39	49	49
CASP1	-0.051	0.17	-9999	-0.42	84	84
IL1RN/IL1R2	-0.06	0.16	-9999	-0.39	82	82
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.057	0.17	-9999	-0.35	111	111
TMEM189-UBE2V1	0	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.003	0.1	-9999	-0.3	50	50
PIK3CA	0.016	0.029	-9999	-0.34	3	3
IL1RN	-0.043	0.16	-9999	-0.4	76	76
TRAF6/TAK1/TAB1/TAB2	0.04	0.031	-9999	-0.26	5	5
MAP2K6	0.028	0.063	-9999	-0.4	2	2

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.016	0.12	-9999	-0.37	46	46
GPC2	0	0	-9999	-10000	0	0
GPC2/Midkine	-0.011	0.083	-9999	-0.26	46	46
neuron projection morphogenesis	-0.011	0.083	-9999	-0.26	46	46

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.042	0.16	-9999	-0.46	67	67
SVIL	-0.004	0.1	-9999	-0.43	27	27
ZNF318	0.014	0.005	-9999	-10000	0	0
JMJD2C	0.023	0.032	-9999	-0.32	4	4
T-DHT/AR/Ubc9	-0.065	0.14	-9999	-0.33	103	103
CARM1	0.014	0.039	-9999	-0.36	5	5
PRDX1	0.012	0.05	-9999	-0.43	6	6
PELP1	0.017	0.001	-9999	-10000	0	0
CTNNB1	0.002	0.09	-9999	-0.45	19	19
AKT1	0.01	0.053	-9999	-0.37	9	9
PTK2B	0.017	0.017	-9999	-0.25	2	2
MED1	-0.001	0.066	-9999	-0.25	34	34
MAK	-0.018	0.094	-9999	-0.28	57	57
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.019	0.012	-9999	-0.25	1	1
GSN	0	0.095	-9999	-0.43	23	23
NCOA2	0.009	0.063	-9999	-0.4	11	11
NCOA6	0.019	0.012	-9999	-0.25	1	1
DNA-PK	0.029	0.029	-9999	-0.31	2	2
NCOA4	0.008	0.069	-9999	-0.45	11	11
PIAS3	0.019	0.002	-9999	-10000	0	0
cell proliferation	-0.043	0.092	-9999	-0.57	9	9
XRCC5	0.017	0.001	-9999	-10000	0	0
UBE3A	0.018	0.033	-9999	-0.52	2	2
T-DHT/AR/SNURF	-0.076	0.14	-9999	-0.32	118	118
FHL2	-0.15	0.34	-9999	-0.97	70	70
RANBP9	0.019	0.012	-9999	-0.25	1	1
JMJD1A	-0.002	0.055	-9999	-10000	0	0
CDK6	-0.019	0.1	-9999	-0.29	63	63
TGFB1I1	-0.003	0.1	-9999	-0.48	23	23
T-DHT/AR/CyclinD1	-0.12	0.21	-9999	-0.43	149	149
XRCC6	0.016	0.012	-9999	-0.26	1	1
T-DHT/AR	-0.085	0.17	-9999	-0.33	138	138
CTDSP1	0.016	0.033	-9999	-0.52	2	2
CTDSP2	0.011	0.044	-9999	-0.42	5	5
BRCA1	0.001	0.094	-9999	-0.48	19	19
TCF4	-0.01	0.12	-9999	-0.51	26	26
CDKN2A	-0.055	0.15	-9999	-0.33	108	108
SRF	0	0.054	-9999	-0.28	4	4
NKX3-1	-0.056	0.11	-9999	-0.24	105	105
KLK3	0.022	0.055	-9999	-10000	0	0
TMF1	0.018	0.001	-9999	-10000	0	0
HNRNPA1	0.015	0.023	-9999	-0.52	1	1
AOF2	0.018	0.026	-9999	-0.39	2	2
APPL1	0.015	0.054	-9999	-0.37	9	9
T-DHT/AR/Caspase 8	-0.066	0.14	-9999	-0.33	103	103
AR	-0.11	0.21	-9999	-0.53	104	104
UBA3	0	0.001	-9999	-10000	0	0
PATZ1	0.003	0.084	-9999	-0.5	14	14
PAWR	0.001	0.091	-9999	-0.44	20	20
PRKDC	0.011	0.045	-9999	-0.31	9	9
PA2G4	0.016	0.012	-9999	-0.26	1	1
UBE2I	0.018	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.059	0.13	-9999	-0.3	103	103
RPS6KA3	0.011	0.057	-9999	-0.34	12	12
T-DHT/AR/ARA70	-0.071	0.15	-9999	-0.34	109	109
LATS2	0.004	0.078	-9999	-0.48	13	13
T-DHT/AR/PRX1	-0.062	0.13	-9999	-0.31	106	106
Cyclin D3/CDK11 p58	0.013	0.008	-9999	-0.17	1	1
VAV3	-0.082	0.2	-9999	-0.48	108	108
KLK2	-0.013	0.075	-9999	-0.4	1	1
CASP8	0.017	0.001	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.054	0.14	-9999	-0.3	111	111
TMPRSS2	-0.18	0.38	-9999	-0.91	105	105
CCND1	-0.089	0.2	-9999	-0.44	124	124
PIAS1	0.019	0.012	-9999	-0.25	1	1
mol:T-DHT	-0.018	0.037	-9999	-0.077	130	130
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.016	0.05	-9999	-0.43	6	6
T-DHT/AR/CDK6	-0.085	0.17	-9999	-0.37	118	118
CMTM2	0.016	0.023	-9999	-0.52	1	1
SNURF	0	0	-9999	-10000	0	0
ZMIZ1	-0.003	0.049	-9999	-0.31	6	6
CCND3	0.017	0.012	-9999	-0.25	1	1
TGIF1	0.006	0.073	-9999	-0.52	10	10
FKBP4	0.013	0.055	-9999	-0.44	7	7

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.045	0.14	-10000	0	-0.37	67	67
fibroblast growth factor receptor signaling pathway	-0.045	0.14	-10000	0	-0.36	67	67
LAMA1	0.015	0.026	-10000	0	-0.25	5	5
PRNP	0.006	0.073	-10000	0	-0.44	13	13
GPC1/SLIT2	-0.025	0.14	-10000	0	-0.39	60	60
SMAD2	0.012	0.084	-10000	0	-0.28	36	36
GPC1/PrPc/Cu2+	0.002	0.083	-10000	0	-0.33	30	30
GPC1/Laminin alpha1	0.007	0.082	-10000	0	-0.37	22	22
TDGF1	0.017	0.012	-10000	0	-0.25	1	1
CRIPTO/GPC1	0.009	0.08	-10000	0	-0.37	22	22
APP/GPC1	-0.025	0.13	-10000	0	-0.38	57	57
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.01	0.081	-10000	0	-0.31	30	30
FLT1	0.004	0.08	-10000	0	-0.45	15	15
GPC1/TGFB/TGFBR1/TGFBR2	0.009	0.093	-10000	0	-0.32	35	35
SERPINC1	0.007	0.054	-10000	0	-0.27	19	19
FYN	0.01	0.079	-10000	0	-0.31	29	29
FGR	0.015	0.068	-10000	0	-0.3	22	22
positive regulation of MAPKKK cascade	-0.012	0.12	-10000	0	-0.39	32	32
SLIT2	-0.029	0.15	-10000	0	-0.48	50	50
GPC1/NRG	0.002	0.089	-10000	0	-0.38	23	23
NRG1	0.008	0.053	-10000	0	-0.27	18	18
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.002	0.097	-10000	0	-0.32	37	37
LYN	0.014	0.071	-10000	0	-0.31	22	22
mol:Spermine	-0.005	0.079	-10000	0	-0.38	22	22
cell growth	-0.045	0.14	-10000	0	-0.36	67	67
BMP signaling pathway	0.006	0.11	0.49	25	-10000	0	25
SRC	0.015	0.073	-10000	0	-0.32	23	23
TGFBR1	0.003	0.082	-10000	0	-0.42	18	18
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.054	0.14	-10000	0	-0.3	122	122
GPC1	-0.006	0.11	-10000	0	-0.49	25	25
TGFBR1 (dimer)	0.003	0.082	-10000	0	-0.42	18	18
VEGFA	0	0.075	-10000	0	-0.29	31	31
BLK	-0.005	0.092	-10000	0	-0.33	30	30
HCK	0.002	0.095	-10000	0	-0.32	41	41
FGF2	-0.064	0.16	-10000	0	-0.34	122	122
FGFR1	-0.013	0.11	-10000	0	-0.35	44	44
VEGFR1 homodimer	0.004	0.08	-10000	0	-0.45	15	15
TGFBR2	0.013	0.049	-10000	0	-0.43	6	6
cell death	-0.025	0.13	-10000	0	-0.38	57	57
ATIII/GPC1	0.002	0.088	-10000	0	-0.38	23	23
PLA2G2A/GPC1	-0.041	0.12	-10000	0	-0.39	41	41
LCK	-0.039	0.13	-10000	0	-0.32	82	82
neuron differentiation	0.002	0.089	-10000	0	-0.38	23	23
PrPc/Cu2+	0.005	0.053	-10000	0	-0.38	9	9
APP	-0.029	0.14	-10000	0	-0.43	56	56
TGFBR2 (dimer)	0.013	0.049	-10000	0	-0.43	6	6

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.018	0.062	-9999	-0.31	17	17
SNTA1	0.011	0.058	-9999	-0.48	7	7
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.004	0.086	-9999	-0.32	31	31
MAPK12	-0.004	0.092	-9999	-0.28	46	46
CCND1	-0.07	0.17	-9999	-0.42	91	91
p38 gamma/SNTA1	0.002	0.093	-9999	-0.26	51	51
MAP2K3	0.014	0.037	-9999	-0.29	7	7
PKN1	0.013	0.045	-9999	-0.39	6	6
G2/M transition checkpoint	-0.004	0.091	-9999	-0.28	46	46
MAP2K6	-0.005	0.091	-9999	-0.3	43	43
MAPT	-0.054	0.15	-9999	-0.32	120	120
MAPK13	0.011	0.071	-9999	-0.38	16	16
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.003	0.072	-9999	-0.33	23	23

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.004	0.088	0.33	33	-10000	0	33
PI3K Class IB/PDE3B	-0.004	0.088	-10000	0	-0.33	33	33
PDE3B	-0.004	0.088	-10000	0	-0.33	33	33

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.019	0.049	-10000	0	-0.51	4	4
HSPA8	0.001	0.09	-10000	0	-0.52	15	15
SMAD3/SMAD4/ER alpha	-0.091	0.2	0.23	5	-0.36	162	167
AKT1	0.01	0.056	-10000	0	-0.37	9	9
GSC	-0.2	0.49	-10000	0	-1.4	77	77
NKX2-5	-0.018	0.093	-10000	0	-0.26	67	67
muscle cell differentiation	0.066	0.16	0.47	46	-10000	0	46
SMAD2-3/SMAD4/SP1	-0.006	0.18	-10000	0	-0.43	57	57
SMAD4	-0.015	0.1	-10000	0	-0.32	33	33
CBFB	0.015	0.037	-10000	0	-0.39	4	4
SAP18	0.017	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.014	0.075	-10000	0	-0.29	8	8
SMAD3/SMAD4/VDR	0.027	0.12	-10000	0	-0.36	27	27
MYC	-0.024	0.14	-10000	0	-0.44	49	49
CDKN2B	-0.047	0.3	-10000	0	-1.3	25	25
AP1	-0.068	0.23	-10000	0	-0.54	76	76
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.037	0.066	-10000	0	-0.28	2	2
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.004	0.12	-10000	0	-0.34	36	36
SP3	0.014	0.02	-10000	0	-10000	0	0
CREB1	0.017	0.023	-10000	0	-0.52	1	1
FOXH1	-0.001	0.042	-10000	0	-10000	0	0
SMAD3/SMAD4/GR	-0.004	0.13	-10000	0	-0.36	44	44
GATA3	-0.099	0.22	-10000	0	-0.5	124	124
SKI/SIN3/HDAC complex/NCoR1	0.042	0.037	-10000	0	-10000	0	0
MEF2C/TIF2	-0.028	0.17	-10000	0	-0.51	40	40
endothelial cell migration	0.018	0.24	1.3	16	-10000	0	16
MAX	0.018	0.009	-10000	0	-10000	0	0
RBBP7	0.01	0.051	-10000	0	-0.3	13	13
RBBP4	0.016	0.026	-10000	0	-0.39	2	2
RUNX2	0.013	0.049	-10000	0	-0.43	6	6
RUNX3	-0.062	0.18	-10000	0	-0.4	101	101
RUNX1	-0.027	0.14	-10000	0	-0.42	54	54
CTBP1	0.017	0.017	-10000	0	-0.25	2	2
NR3C1	-0.001	0.099	-10000	0	-0.51	19	19
VDR	-0.003	0.1	-10000	0	-0.51	21	21
CDKN1A	-0.03	0.27	-10000	0	-1.3	18	18
KAT2B	0.001	0.006	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.016	0.13	-10000	0	-0.32	48	48
DCP1A	0.017	0.023	-10000	0	-0.52	1	1
SKI	0.016	0.017	-10000	0	-0.25	2	2
SERPINE1	-0.019	0.24	-10000	0	-1.3	16	16
SMAD3/SMAD4/ATF2	0.006	0.11	-10000	0	-0.33	30	30
SMAD3/SMAD4/ATF3	-0.017	0.14	-10000	0	-0.35	55	55
SAP30	0.012	0.053	-10000	0	-0.48	6	6
Cbp/p300/PIAS3	0.047	0.053	-10000	0	-0.29	6	6
JUN	-0.07	0.22	-10000	0	-0.54	75	75
SMAD3/SMAD4/IRF7	0.002	0.13	-10000	0	-0.37	36	36
TFE3	0.018	0.026	-10000	0	-10000	0	0
COL1A2	-0.1	0.37	-10000	0	-1	72	72
mesenchymal cell differentiation	-0.003	0.11	0.35	33	-10000	0	33
DLX1	-0.009	0.081	-10000	0	-0.25	53	53
TCF3	0.013	0.044	-10000	0	-0.32	8	8
FOS	-0.11	0.2	-10000	0	-0.38	171	171
SMAD3/SMAD4/Max	0.008	0.11	-10000	0	-0.33	30	30
Cbp/p300/SNIP1	0.035	0.046	-10000	0	-0.3	9	9
ZBTB17	0.019	0.012	-10000	0	-10000	0	0
LAMC1	0.003	0.15	-10000	0	-0.53	30	30
TGIF2/HDAC complex/SMAD3/SMAD4	0.001	0.12	-10000	0	-0.35	36	36
IRF7	0.007	0.079	-10000	0	-0.49	12	12
ESR1	-0.15	0.24	-10000	0	-0.46	182	182
HNF4A	0.016	0.033	-10000	0	-0.52	2	2
MEF2C	-0.035	0.18	-10000	0	-0.54	40	40
SMAD2-3/SMAD4	-0.008	0.12	-10000	0	-0.34	40	40
Cbp/p300/Src-1	0.036	0.055	-10000	0	-0.28	12	12
IGHV3OR16-13	-0.017	0.039	-10000	0	-0.52	1	1
TGIF2/HDAC complex	0.009	0.066	-10000	0	-0.42	11	11
CREBBP	0.019	0.034	-10000	0	-0.51	2	2
SKIL	0.005	0.07	-10000	0	-0.34	19	19
HDAC1	0.016	0.023	-10000	0	-0.52	1	1
HDAC2	0.008	0.053	-10000	0	-0.29	15	15
SNIP1	0.014	0.041	-10000	0	-0.52	3	3
GCN5L2	0.018	0.044	-10000	0	-0.46	4	4
SMAD3/SMAD4/TFE3	0.014	0.12	-10000	0	-0.33	44	44
MSG1/HSC70	-0.019	0.097	-10000	0	-0.41	16	16
SMAD2	-0.002	0.051	-10000	0	-0.51	1	1
SMAD3	-0.004	0.1	-10000	0	-0.47	17	17
SMAD3/E2F4-5/DP1/p107/SMAD4	0.008	0.097	-10000	0	-0.29	28	28
SMAD2/SMAD2/SMAD4	-0.007	0.055	-10000	0	-0.3	10	10
NCOR1	0.015	0.033	-10000	0	-0.52	2	2
NCOA2	0.009	0.063	-10000	0	-0.4	11	11
NCOA1	0.012	0.057	-10000	0	-0.52	6	6
MYOD/E2A	-0.001	0.097	-10000	0	-0.37	31	31
SMAD2-3/SMAD4/SP1/MIZ-1	0.007	0.17	-10000	0	-0.43	47	47
IFNB1	0.005	0.13	-10000	0	-0.43	27	27
SMAD3/SMAD4/MEF2C	-0.027	0.2	-10000	0	-0.55	47	47
CITED1	-0.029	0.1	-10000	0	-0.26	89	89
SMAD2-3/SMAD4/ARC105	0.009	0.12	-10000	0	-0.34	25	25
RBL1	0.01	0.048	-10000	0	-0.27	14	14
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.001	0.15	-10000	0	-0.48	35	35
RUNX1-3/PEBPB2	-0.042	0.14	-10000	0	-0.34	86	86
SMAD7	-0.042	0.23	-10000	0	-0.6	49	49
MYC/MIZ-1	-0.003	0.1	-10000	0	-0.36	34	34
SMAD3/SMAD4	0.046	0.14	0.3	39	-0.4	15	54
IL10	-0.046	0.18	-10000	0	-0.39	82	82
PIASy/HDAC complex	0.009	0.051	-10000	0	-0.44	6	6
PIAS3	0.019	0.005	-10000	0	-10000	0	0
CDK2	0.015	0.048	-10000	0	-0.3	10	10
IL5	-0.047	0.18	-10000	0	-0.38	80	80
CDK4	0.019	0.029	-10000	0	-0.25	5	5
PIAS4	0.009	0.051	-10000	0	-0.44	6	6
ATF3	-0.02	0.13	-10000	0	-0.41	47	47
SMAD3/SMAD4/SP1	-0.01	0.18	-10000	0	-0.42	61	61
FOXG1	-0.007	0.083	-10000	0	-0.27	45	45
FOXO3	0.015	0.061	-10000	0	-0.4	8	8
FOXO1	0.007	0.081	-10000	0	-0.37	20	20
FOXO4	0.019	0.047	-10000	0	-0.37	5	5
heart looping	-0.034	0.17	-10000	0	-0.53	40	40
CEBPB	0.004	0.073	-10000	0	-0.34	20	20
SMAD3/SMAD4/DLX1	-0.01	0.12	-10000	0	-0.33	38	38
MYOD1	-0.015	0.13	-10000	0	-0.47	36	36
SMAD3/SMAD4/HNF4	0.005	0.11	-10000	0	-0.32	33	33
SMAD3/SMAD4/GATA3	-0.062	0.2	-10000	0	-0.38	127	127
SnoN/SIN3/HDAC complex/NCoR1	0.005	0.07	-10000	0	-0.34	19	19
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.036	0.17	-10000	0	-0.34	100	100
SMAD3/SMAD4/SP1-3	-0.001	0.19	-10000	0	-0.47	53	53
MED15	0.018	0	-10000	0	-10000	0	0
SP1	-0.002	0.069	-10000	0	-0.23	18	18
SIN3B	0.017	0.012	-10000	0	-0.25	1	1
SIN3A	0.017	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.02	0.15	-10000	0	-0.38	45	45
ITGB5	-0.032	0.23	-10000	0	-0.65	56	56
TGIF/SIN3/HDAC complex/CtBP	0.041	0.042	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.061	0.19	-10000	0	-0.39	117	117
AR	-0.088	0.21	-10000	0	-0.52	104	104
negative regulation of cell growth	-0.002	0.12	-10000	0	-0.36	33	33
SMAD3/SMAD4/MYOD	-0.016	0.13	-10000	0	-0.32	59	59
E2F5	-0.014	0.12	-10000	0	-0.39	41	41
E2F4	0.017	0.017	-10000	0	-0.25	2	2
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.01	0.11	-10000	0	-0.32	18	18
SMAD2-3/SMAD4/FOXO1-3a-4	0.005	0.13	-10000	0	-0.36	41	41
TFDP1	0.011	0.042	-10000	0	-0.25	13	13
SMAD3/SMAD4/AP1	-0.064	0.24	-10000	0	-0.55	75	75
SMAD3/SMAD4/RUNX2	0.003	0.12	-10000	0	-0.35	33	33
TGIF2	0.009	0.066	-10000	0	-0.42	11	11
TGIF1	0.008	0.073	-10000	0	-0.52	10	10
ATF2	0.018	0	-10000	0	-10000	0	0

×

TRAIL 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
TNFSF10	-0.042	0.16	-10000	0	-0.46	67	67
positive regulation of NF-kappaB transcription factor activity	-0.019	0.12	-10000	0	-0.37	52	52
MAP2K4	-0.013	0.12	-10000	0	-0.38	28	28
IKBKB	0.012	0.047	-10000	0	-0.31	10	10
TNFRSF10B	0.005	0.079	-10000	0	-0.46	14	14
TNFRSF10A	-0.004	0.1	-10000	0	-0.47	24	24
SMPD1	-0.008	0.086	-10000	0	-0.23	58	58
IKBKG	0.018	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.015	0.031	-10000	0	-0.32	4	4
TRAIL/TRAILR2	-0.026	0.14	-10000	0	-0.4	57	57
TRAIL/TRAILR3	-0.032	0.13	-10000	0	-0.37	54	54
TRAIL/TRAILR1	-0.032	0.14	-10000	0	-0.4	64	64
TRAIL/TRAILR4	-0.019	0.12	-10000	0	-0.37	52	52
TRAIL/TRAILR1/DAP3/GTP	-0.013	0.12	-10000	0	-0.3	65	65
IKK complex	-0.028	0.082	-10000	0	-0.42	15	15
RIPK1	0.017	0.023	-10000	0	-0.52	1	1
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.012	0.019	-10000	0	-0.27	2	2
MAPK3	-0.019	0.12	-10000	0	-0.37	52	52
MAP3K1	-0.01	0.12	-10000	0	-0.38	26	26
TRAILR4 (trimer)	0.015	0.031	-10000	0	-0.32	4	4
TRADD	0.016	0.026	-10000	0	-0.39	2	2
TRAILR1 (trimer)	-0.004	0.1	-10000	0	-0.46	24	24
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.004	0.11	-10000	0	-0.43	13	13
CFLAR	0.009	0.065	-10000	0	-0.44	10	10
MAPK1	-0.02	0.12	-10000	0	-0.37	53	53
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.002	0.12	-10000	0	-0.29	64	64
mol:ceramide	-0.008	0.086	-10000	0	-0.23	58	58
FADD	0	0.067	-10000	0	-0.25	35	35
MAPK8	-0.007	0.12	-10000	0	-0.39	23	23
TRAF2	0.014	0.042	-10000	0	-0.45	4	4
TRAILR3 (trimer)	-0.004	0.075	-10000	0	-0.26	41	41
CHUK	0.005	0.081	-10000	0	-0.5	13	13
TRAIL/TRAILR1/FADD	-0.025	0.13	-10000	0	-0.34	65	65
DAP3	0.016	0.026	-10000	0	-0.39	2	2
CASP10	-0.05	0.12	0.26	1	-0.36	54	55
JNK cascade	-0.019	0.12	-10000	0	-0.37	52	52
TRAIL (trimer)	-0.042	0.16	-10000	0	-0.46	67	67
TNFRSF10C	-0.004	0.075	-10000	0	-0.26	41	41
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.011	0.12	-10000	0	-0.29	65	65
TRAIL/TRAILR2/FADD	-0.019	0.13	-10000	0	-0.34	58	58
cell death	-0.008	0.086	-10000	0	-0.23	58	58
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0	0.11	-10000	0	-0.27	59	59
TRAILR2 (trimer)	0.005	0.079	-10000	0	-0.46	14	14
CASP8	0.01	0.042	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.003	0.12	-10000	0	-0.29	56	56

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.037	0.17	-9999	-0.45	74	74
KLHL20	-0.015	0.099	-9999	-0.25	25	25
CYFIP2	-0.042	0.16	-9999	-0.47	65	65
Rac1/GDP	0.006	0.11	-9999	-0.25	74	74
ENAH	-0.036	0.18	-9999	-0.45	76	76
AP1M1	0.017	0.023	-9999	-0.52	1	1
RAP1B	0.013	0.044	-9999	-0.32	8	8
RAP1A	0.012	0.057	-9999	-0.52	6	6
CTNNB1	0.001	0.09	-9999	-0.45	19	19
CDC42/GTP	-0.032	0.069	-9999	-0.3	10	10
ABI1/Sra1/Nap1	-0.042	0.054	-9999	-0.17	36	36
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.005	0.12	-9999	-0.28	79	79
RAPGEF1	-0.015	0.15	-9999	-0.38	74	74
CTNND1	0.016	0.029	-9999	-0.34	3	3
regulation of calcium-dependent cell-cell adhesion	-0.039	0.17	-9999	-0.46	74	74
CRK	-0.024	0.16	-9999	-0.41	74	74
E-cadherin/gamma catenin/alpha catenin	-0.01	0.12	-9999	-0.31	65	65
alphaE/beta7 Integrin	0.023	0.038	-9999	-0.37	5	5
IQGAP1	0.018	0	-9999	-10000	0	0
NCKAP1	0.015	0.031	-9999	-0.32	4	4
Rap1/GTP/I-afadin	0.014	0.073	-9999	-0.28	28	28
DLG1	-0.031	0.17	-9999	-0.44	74	74
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.028	0.055	-9999	-0.22	15	15
MLLT4	-0.006	0.11	-9999	-0.46	26	26
ARF6/GTP/NME1/Tiam1	0.023	0.052	-9999	-0.3	10	10
PI3K	-0.036	0.07	-9999	-0.29	13	13
ARF6	0.016	0.033	-9999	-0.52	2	2
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.027	0.13	-9999	-0.37	64	64
TIAM1	0.006	0.073	-9999	-0.44	13	13
E-cadherin(dimer)/Ca2+	-0.005	0.11	-9999	-0.26	76	76
AKT1	-0.022	0.043	-9999	-0.17	14	14
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
CDH1	-0.049	0.17	-9999	-0.48	70	70
RhoA/GDP	0.003	0.12	-9999	-0.32	27	27
actin cytoskeleton organization	-0.009	0.075	-9999	-0.18	25	25
CDC42/GDP	0.008	0.11	-9999	-0.29	23	23
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.007	0.09	-9999	-0.24	66	66
ITGB7	0.018	0	-9999	-10000	0	0
RAC1	0.018	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.005	0.11	-9999	-0.28	76	76
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.014	0.1	-9999	-0.27	75	75
mol:GDP	-0.004	0.13	-9999	-0.3	75	75
CDC42/GTP/IQGAP1	0.024	0	-9999	-10000	0	0
JUP	0.011	0.056	-9999	-0.42	8	8
p120 catenin/RhoA/GDP	0.002	0.12	-9999	-0.34	20	20
RAC1/GTP/IQGAP1	0.024	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.023	0.035	-9999	-0.37	4	4
RHOA	0.005	0.08	-9999	-0.52	12	12
CDC42	0.018	0	-9999	-10000	0	0
CTNNA1	0.017	0.023	-9999	-0.52	1	1
positive regulation of S phase of mitotic cell cycle	-0.027	0.094	-9999	-0.2	97	97
NME1	0.012	0.039	-9999	-0.25	11	11
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.033	0.17	-9999	-0.44	75	75
regulation of cell-cell adhesion	-0.029	0.061	-9999	-0.26	10	10
WASF2	-0.021	0.031	-9999	-0.15	2	2
Rap1/GTP	-0.038	0.08	-9999	-0.34	10	10
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.009	0.1	-9999	-0.25	70	70
CCND1	-0.035	0.12	-9999	-0.26	95	95
VAV2	-0.022	0.16	-9999	-0.4	74	74
RAP1/GDP	0.005	0.11	-9999	-0.36	9	9
adherens junction assembly	-0.031	0.17	-9999	-0.43	75	75
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.016	0.02	-9999	-0.25	3	3
PIP5K1C	0.014	0.042	-9999	-0.45	4	4
regulation of heterotypic cell-cell adhesion	0.006	0.11	-9999	-0.33	7	7
E-cadherin/beta catenin	-0.045	0.11	-9999	-0.34	64	64
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.033	0.17	-9999	-0.44	75	75
PIK3CA	0.016	0.029	-9999	-0.34	3	3
Rac1/GTP	-0.078	0.12	-9999	-0.42	27	27
E-cadherin/beta catenin/alpha catenin	-0.017	0.12	-9999	-0.31	75	75
ITGAE	0.013	0.052	-9999	-0.52	5	5
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.04	0.18	-9999	-0.47	74	74

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.025	0.076	-10000	0	-0.64	6	6
HDAC1	0.022	0.03	-10000	0	-0.53	1	1
AES	0.019	0.006	-10000	0	-10000	0	0
FBXW11	0.015	0.035	-10000	0	-0.43	3	3
DTX1	0.012	0.049	-10000	0	-0.34	9	9
LRP6/FZD1	0.009	0.076	-10000	0	-0.36	19	19
TLE1	-0.031	0.15	-10000	0	-0.45	56	56
AP1	-0.05	0.13	-10000	0	-0.3	82	82
NCSTN	0.017	0.023	-10000	0	-0.52	1	1
ADAM10	0.013	0.045	-10000	0	-0.39	6	6
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.041	0.13	-10000	0	-0.42	8	8
NICD/RBPSUH	0.027	0.076	-10000	0	-0.63	6	6
WIF1	-0.024	0.098	-10000	0	-0.25	81	81
NOTCH1	-0.003	0.077	-10000	0	-0.67	6	6
PSENEN	0.017	0.012	-10000	0	-0.25	1	1
KREMEN2	-0.19	0.23	-10000	0	-0.41	257	257
DKK1	-0.12	0.19	-10000	0	-0.34	199	199
beta catenin/beta TrCP1	0.004	0.084	0.24	4	-0.35	17	21
APH1B	0.001	0.093	-10000	0	-0.51	17	17
APH1A	0.003	0.067	-10000	0	-0.29	25	25
AXIN1	0.006	0.04	0.24	8	-0.23	3	11
CtBP/CBP/TCF1/TLE1/AES	0.036	0.1	0.29	5	-0.26	1	6
PSEN1	0.013	0.052	-10000	0	-0.52	5	5
FOS	-0.11	0.2	-10000	0	-0.37	171	171
JUN	-0.034	0.15	-10000	0	-0.46	57	57
MAP3K7	0.019	0.022	-10000	0	-0.26	3	3
CTNNB1	-0.005	0.084	0.23	6	-0.38	15	21
MAPK3	0.016	0.026	-10000	0	-0.39	2	2
DKK2/LRP6/Kremen 2	-0.12	0.16	-10000	0	-0.33	186	186
HNF1A	0.017	0.026	-10000	0	-0.24	5	5
CTBP1	0.018	0.018	-10000	0	-0.26	2	2
MYC	-0.086	0.34	-10000	0	-1.4	34	34
NKD1	0.01	0.059	-10000	0	-0.38	11	11
FZD1	0.003	0.082	-10000	0	-0.43	17	17
NOTCH1 precursor/Deltex homolog 1	0.024	0.085	-10000	0	-0.69	6	6
apoptosis	-0.05	0.12	-10000	0	-0.3	82	82
Delta 1/NOTCHprecursor	0.027	0.076	-10000	0	-0.63	6	6
DLL1	0.017	0.012	-10000	0	-0.25	1	1
PPARD	0.004	0.045	-10000	0	-10000	0	0
Gamma Secretase	0.031	0.069	-10000	0	-0.25	25	25
APC	0.002	0.055	0.24	7	-0.35	7	14
DVL1	0.022	0.038	-10000	0	-0.38	3	3
CSNK2A1	0.016	0.023	-10000	0	-0.52	1	1
MAP3K7IP1	0.02	0.008	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.17	0.17	-10000	0	-0.34	249	249
LRP6	0.008	0.065	-10000	0	-0.38	13	13
CSNK1A1	0.016	0.024	-10000	0	-0.52	1	1
NLK	0.032	0.03	-10000	0	-0.26	1	1
CCND1	-0.22	0.51	-10000	0	-1.4	87	87
WNT1	0.017	0.023	-10000	0	-0.52	1	1
Axin1/APC/beta catenin	0.017	0.074	0.28	4	-0.35	6	10
DKK2	-0.026	0.14	-10000	0	-0.42	52	52
NOTCH1 precursor/DVL1	0.036	0.077	-10000	0	-0.54	7	7
GSK3B	0.018	0.001	-10000	0	-10000	0	0
FRAT1	0.01	0.068	-10000	0	-0.47	10	10
NOTCH/Deltex homolog 1	0.022	0.085	-10000	0	-0.7	6	6
PPP2R5D	0.013	0.036	0.27	5	-10000	0	5
MAPK1	0.016	0.033	-10000	0	-0.52	2	2
WNT1/LRP6/FZD1	0.009	0.079	-10000	0	-0.27	23	23
RBPJ	0.018	0	-10000	0	-10000	0	0
CREBBP	0.013	0.035	-10000	0	-0.52	2	2

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.003	0.068	-9999	-0.28	26	26
Syndecan-3/Src/Cortactin	-0.046	0.16	-9999	-0.52	35	35
Syndecan-3/Neurocan	-0.007	0.13	-9999	-0.57	24	24
POMC	0.001	0.072	-9999	-0.28	30	30
EGFR	-0.079	0.18	-9999	-0.35	139	139
Syndecan-3/EGFR	-0.049	0.16	-9999	-0.39	68	68
AGRP	0.016	0.029	-9999	-0.34	3	3
NCSTN	0.017	0.023	-9999	-0.52	1	1
PSENEN	0.017	0.012	-9999	-0.25	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.001	0.093	-9999	-0.51	17	17
APH1A	0.003	0.067	-9999	-0.29	25	25
NCAN	0.007	0.053	-9999	-0.25	21	21
long-term memory	-0.003	0.13	-9999	-0.55	25	25
Syndecan-3/IL8	-0.045	0.16	-9999	-0.42	58	58
PSEN1	0.013	0.052	-9999	-0.52	5	5
Src/Cortactin	0.014	0.054	-9999	-0.37	5	5
FYN	0.008	0.067	-9999	-0.41	12	12
limb bud formation	-0.031	0.12	-9999	-0.59	24	24
MC4R	0.014	0.039	-9999	-0.36	5	5
SRC	0.015	0.035	-9999	-0.43	3	3
PTN	-0.099	0.19	-9999	-0.37	158	158
FGFR/FGF/Syndecan-3	-0.032	0.12	-9999	-0.6	24	24
neuron projection morphogenesis	-0.045	0.16	-9999	-0.47	40	40
Syndecan-3/AgRP	-0.003	0.13	-9999	-0.56	25	25
Syndecan-3/AgRP/MC4R	0.006	0.13	-9999	-0.56	24	24
Fyn/Cortactin	0.009	0.068	-9999	-0.38	10	10
SDC3	-0.032	0.13	-9999	-0.61	24	24
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.044	0.15	-9999	-0.41	58	58
IL8	-0.072	0.17	-9999	-0.34	135	135
Syndecan-3/Fyn/Cortactin	-0.003	0.13	-9999	-0.57	25	25
Syndecan-3/CASK	-0.03	0.12	-9999	-0.58	24	24
alpha-MSH/MC4R	0.012	0.057	-9999	-0.37	5	5
Gamma Secretase	0.033	0.069	-9999	-0.25	25	25

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.01	0.066	-9999	-0.52	8	8
alphaV beta3 Integrin	0.001	0.094	-9999	-0.4	22	22
PTK2	-0.001	0.15	-9999	-0.46	42	42
positive regulation of JNK cascade	-0.028	0.086	-9999	-0.31	43	43
CDC42/GDP	0.021	0.13	-9999	-0.42	41	41
Rac1/GDP	0.023	0.13	-9999	-0.41	41	41
RAP1B	0.013	0.044	-9999	-0.32	8	8
RAP1A	0.012	0.057	-9999	-0.52	6	6
CTNNB1	0.001	0.09	-9999	-0.45	19	19
CDC42/GTP	-0.033	0.11	-9999	-0.38	43	43
nectin-3/I-afadin	-0.016	0.12	-9999	-0.41	41	41
RAPGEF1	0.009	0.15	-9999	-0.47	41	41
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.001	0.17	-9999	-0.54	41	41
PDGFB-D/PDGFRB	0.01	0.066	-9999	-0.52	8	8
TLN1	0.004	0.099	-9999	-0.4	20	20
Rap1/GTP	-0.031	0.093	-9999	-0.33	42	42
IQGAP1	0.018	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.015	0.073	-9999	-0.28	28	28
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.016	0.12	-9999	-0.41	41	41
PVR	0.008	0.059	-9999	-0.33	14	14
Necl-5(dimer)	0.008	0.059	-9999	-0.33	14	14
mol:GDP	0.011	0.16	-9999	-0.51	41	41
MLLT4	-0.006	0.11	-9999	-0.46	26	26
PIK3CA	0.016	0.029	-9999	-0.34	3	3
PI3K	0.001	0.13	-9999	-0.32	59	59
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.007	0.082	-9999	-0.38	21	21
positive regulation of lamellipodium assembly	-0.028	0.088	-9999	-0.32	41	41
PVRL1	0.014	0.035	-9999	-0.3	6	6
PVRL3	-0.019	0.12	-9999	-0.4	46	46
PVRL2	0.002	0.089	-9999	-0.52	15	15
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
CDH1	-0.049	0.17	-9999	-0.48	70	70
CLDN1	-0.11	0.21	-9999	-0.4	165	165
JAM-A/CLDN1	-0.065	0.16	-9999	-0.32	128	128
SRC	-0.01	0.18	-9999	-0.61	41	41
ITGB3	0.002	0.075	-9999	-0.32	25	25
nectin-1(dimer)/I-afadin/I-afadin	0.007	0.082	-9999	-0.38	21	21
FARP2	0.006	0.16	-9999	-0.51	43	43
RAC1	0.018	0	-9999	-10000	0	0
CTNNA1	0.017	0.023	-9999	-0.52	1	1
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.006	0.11	-9999	-0.35	44	44
nectin-1/I-afadin	0.007	0.082	-9999	-0.38	21	21
nectin-2/I-afadin	-0.002	0.1	-9999	-0.39	33	33
RAC1/GTP/IQGAP1/filamentous actin	0.024	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.002	0.11	-9999	-0.34	43	43
CDC42/GTP/IQGAP1/filamentous actin	0.024	0	-9999	-10000	0	0
F11R	0.011	0.055	-9999	-0.36	10	10
positive regulation of filopodium formation	-0.028	0.086	-9999	-0.31	43	43
alphaV/beta3 Integrin/Talin	0.006	0.13	-9999	-0.48	20	20
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.002	0.1	-9999	-0.39	33	33
nectin-2(dimer)/I-afadin/I-afadin	-0.002	0.1	-9999	-0.39	33	33
PIP5K1C	-0.004	0.1	-9999	-0.42	21	21
VAV2	0.006	0.16	-9999	-0.52	41	41
RAP1/GDP	0.019	0.13	-9999	-0.38	42	42
ITGAV	-0.002	0.1	-9999	-0.48	21	21
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.01	0.12	-9999	-0.35	53	53
nectin-3(dimer)/I-afadin/I-afadin	-0.016	0.12	-9999	-0.41	41	41
Rac1/GTP	-0.032	0.11	-9999	-0.4	41	41
PTPRM	-0.011	0.11	-9999	-0.31	47	47
E-cadherin/beta catenin/alpha catenin	-0.012	0.13	-9999	-0.46	11	11
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.018	0	-9999	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.023	0.028	-9999	-0.37	1	1
VLDLR	-0.061	0.17	-9999	-0.4	100	100
CRKL	0.014	0.047	-9999	-0.52	4	4
LRPAP1	0.016	0.026	-9999	-0.39	2	2
FYN	0.008	0.067	-9999	-0.41	12	12
ITGA3	-0.003	0.096	-9999	-0.41	25	25
RELN/VLDLR/Fyn	-0.023	0.12	-9999	-0.32	64	64
MAPK8IP1/MKK7/MAP3K11/JNK1	0.038	0.061	-9999	-0.36	2	2
AKT1	-0.011	0.11	-9999	-0.42	15	15
MAP2K7	0.017	0.023	-9999	-0.52	1	1
RAPGEF1	0.018	0	-9999	-10000	0	0
DAB1	0.018	0	-9999	-10000	0	0
RELN/LRP8/DAB1	-0.011	0.094	-9999	-0.28	42	42
LRPAP1/LRP8	-0.027	0.11	-9999	-0.37	37	37
RELN/LRP8/DAB1/Fyn	-0.006	0.096	-9999	-0.26	48	48
DAB1/alpha3/beta1 Integrin	-0.067	0.11	-9999	-0.37	26	26
long-term memory	-0.002	0.1	-9999	-0.39	6	6
DAB1/LIS1	-0.028	0.12	-9999	-0.25	93	93
DAB1/CRLK/C3G	-0.059	0.097	-9999	-0.37	16	16
PIK3CA	0.016	0.029	-9999	-0.34	3	3
DAB1/NCK2	-0.029	0.12	-9999	-0.25	94	94
ARHGEF2	0.004	0.079	-9999	-0.41	17	17
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	0.017	0.012	-9999	-0.25	1	1
CDK5R1	0.014	0.031	-9999	-0.25	7	7
RELN	0.01	0.059	-9999	-0.38	11	11
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
RELN/LRP8/Fyn	-0.02	0.11	-9999	-0.32	48	48
GRIN2A/RELN/LRP8/DAB1/Fyn	0.004	0.097	-9999	-0.26	47	47
MAPK8	0.015	0.04	-9999	-0.52	3	3
RELN/VLDLR/DAB1	-0.014	0.1	-9999	-0.28	59	59
ITGB1	0.014	0.044	-9999	-0.41	5	5
MAP1B	-0.058	0.15	-9999	-0.3	111	111
RELN/LRP8	-0.015	0.1	-9999	-0.31	43	43
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.009	0.11	-9999	-0.26	65	65
PI3K	0.005	0.082	-9999	-0.37	21	21
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.009	0.078	-9999	-0.39	17	17
RAP1A	-0.019	0.12	-9999	-0.36	17	17
PAFAH1B1	0.017	0.023	-9999	-0.52	1	1
MAPK8IP1	0.011	0.048	-9999	-0.3	11	11
CRLK/C3G	0.023	0.034	-9999	-0.37	4	4
GRIN2B	-0.007	0.1	-9999	-0.44	28	28
NCK2	0.015	0.026	-9999	-0.25	5	5
neuron differentiation	0.011	0.079	-9999	-0.33	4	4
neuron adhesion	-0.016	0.12	-9999	-0.33	28	28
LRP8	-0.057	0.16	-9999	-0.34	110	110
GSK3B	-0.004	0.1	-9999	-0.4	14	14
RELN/VLDLR/DAB1/Fyn	-0.009	0.11	-9999	-0.27	64	64
MAP3K11	0.015	0.035	-9999	-0.43	3	3
RELN/VLDLR/DAB1/P13K	-0.016	0.11	-9999	-0.26	74	74
CDK5	0.016	0.026	-9999	-0.39	2	2
MAPT	-0.089	0.2	-9999	-0.48	107	107
neuron migration	-0.013	0.12	-9999	-0.35	27	27
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.011	0.079	-9999	-0.34	4	4
RELN/VLDLR	-0.045	0.14	-9999	-0.28	113	113

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.019	0.061	-9999	-0.27	21	21
RGS9BP	-0.072	0.18	-9999	-0.41	111	111
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
mol:Na +	-0.016	0.089	-9999	-0.33	24	24
mol:ADP	0.011	0.025	-9999	-0.31	3	3
GNAT2	-0.004	0.1	-9999	-0.49	23	23
RGS9-1/Gbeta5/R9AP	-0.056	0.15	-9999	-0.34	96	96
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.089	-9999	-0.33	33	33
GRK7	0.015	0.035	-9999	-0.43	3	3
CNGB3	-0.006	0.086	-9999	-0.3	39	39
Cone Metarhodopsin II/X-Arrestin	0.013	0.008	-9999	-0.17	1	1
mol:Ca2+	-0.009	0.083	-9999	-0.29	27	27
Cone PDE6	-0.043	0.14	-9999	-0.29	114	114
Cone Metarhodopsin II	0.01	0.019	-9999	-0.24	3	3
Na + (4 Units)	-0.005	0.085	-9999	-0.29	27	27
GNAT2/GDP	-0.049	0.14	-9999	-0.29	112	112
GNB5	0.005	0.081	-9999	-0.5	13	13
mol:GMP (4 units)	0.001	0.091	-9999	-0.31	37	37
Cone Transducin	0.02	0.065	-9999	-0.29	21	21
SLC24A2	0.014	0.044	-9999	-0.41	5	5
GNB3/GNGT2	0.025	0.026	-9999	-0.37	2	2
GNB3	0.017	0.012	-9999	-0.25	1	1
GNAT2/GTP	-0.003	0.076	-9999	-0.35	23	23
CNGA3	-0.028	0.12	-9999	-0.31	73	73
ARR3	0.017	0.012	-9999	-0.25	1	1
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.016	0.089	-9999	-0.33	24	24
mol:Pi	-0.056	0.15	-9999	-0.34	96	96
Cone CNG Channel	-0.014	0.11	-9999	-0.3	53	53
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0.014	0.044	-9999	-0.41	5	5
RGS9	-0.033	0.13	-9999	-0.31	81	81
PDE6C	0.008	0.065	-9999	-0.38	13	13
GNGT2	0.016	0.033	-9999	-0.52	2	2
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.001	0.093	-9999	-0.44	21	21

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.024	0.14	-10000	0	-0.46	46	46
ANTXR2	0.002	0.09	-10000	0	-0.5	16	16
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.007	0.021	-10000	0	-0.074	44	44
monocyte activation	-0.022	0.12	-10000	0	-0.41	41	41
MAP2K2	0.007	0.06	-10000	0	-0.77	3	3
MAP2K1	0.005	0.021	-10000	0	-0.095	7	7
MAP2K7	0.005	0.024	-10000	0	-0.27	1	1
MAP2K6	-0.009	0.063	-10000	0	-0.21	37	37
CYAA	-0.014	0.092	-10000	0	-0.3	44	44
MAP2K4	-0.006	0.056	-10000	0	-0.21	31	31
IL1B	-0.03	0.095	-10000	0	-0.28	55	55
Channel	-0.009	0.1	-10000	0	-0.32	44	44
NLRP1	0.002	0.036	-10000	0	-0.2	9	9
CALM1	0.018	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.007	0.027	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.007	0.021	0.074	44	-10000	0	44
MAPK3	0.005	0.024	-10000	0	-0.19	2	2
MAPK1	0.004	0.027	-10000	0	-0.27	2	2
PGR	-0.14	0.12	-10000	0	-0.27	215	215
PA/Cellular Receptors	-0.011	0.11	-10000	0	-0.35	44	44
apoptosis	-0.007	0.021	-10000	0	-0.074	44	44
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.008	0.094	-10000	0	-0.3	44	44
macrophage activation	0.011	0.028	-10000	0	-0.25	3	3
TNF	-0.004	0.094	-10000	0	-0.36	31	31
VCAM1	-0.022	0.12	-10000	0	-0.42	41	41
platelet activation	0.007	0.027	-10000	0	-10000	0	0
MAPKKK cascade	-0.001	0.034	0.12	18	-10000	0	18
IL18	-0.031	0.11	-10000	0	-0.28	67	67
negative regulation of macrophage activation	-0.007	0.021	-10000	0	-0.074	44	44
LEF	-0.007	0.021	-10000	0	-0.074	44	44
CASP1	-0.006	0.042	-10000	0	-0.098	60	60
mol:cAMP	0.007	0.027	-10000	0	-10000	0	0
necrosis	-0.007	0.021	-10000	0	-0.074	44	44
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.008	0.095	-10000	0	-0.3	44	44
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.025	0.13	-9999	-0.5	37	37
PDGF/PDGFRA/CRKL	-0.006	0.1	-9999	-0.37	36	36
positive regulation of JUN kinase activity	0.019	0.077	-9999	-0.26	34	34
CRKL	0.014	0.047	-9999	-0.52	4	4
PDGF/PDGFRA/Caveolin-3	-0.004	0.097	-9999	-0.37	33	33
AP1	-0.18	0.34	-9999	-0.91	84	84
mol:IP3	-0.015	0.1	-9999	-0.39	33	33
PLCG1	-0.015	0.1	-9999	-0.39	33	33
PDGF/PDGFRA/alphaV Integrin	-0.017	0.12	-9999	-0.4	47	47
RAPGEF1	0.018	0	-9999	-10000	0	0
CRK	0.016	0.033	-9999	-0.52	2	2
mol:Ca2+	-0.015	0.1	-9999	-0.39	33	33
CAV3	0.016	0.029	-9999	-0.34	3	3
CAV1	-0.001	0.083	-9999	-0.33	29	29
SHC/Grb2/SOS1	0.02	0.077	-9999	-0.27	34	34
PDGF/PDGFRA/Shf	-0.009	0.1	-9999	-0.34	40	40
FOS	-0.17	0.34	-9999	-0.89	84	84
JUN	-0.051	0.11	-9999	-0.38	52	52
oligodendrocyte development	-0.017	0.12	-9999	-0.4	47	47
GRB2	0.016	0.024	-9999	-0.25	4	4
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
mol:DAG	-0.015	0.1	-9999	-0.39	33	33
PDGF/PDGFRA	-0.025	0.13	-9999	-0.5	37	37
actin cytoskeleton reorganization	-0.01	0.11	-9999	-0.39	38	38
SRF	0.028	0.025	-9999	-0.35	1	1
SHC1	0.017	0.023	-9999	-0.52	1	1
PI3K	-0.007	0.11	-9999	-0.34	49	49
PDGF/PDGFRA/Crk/C3G	0.01	0.085	-9999	-0.31	33	33
JAK1	-0.009	0.1	-9999	-0.38	37	37
ELK1/SRF	0.012	0.083	-9999	-0.28	36	36
SHB	0.008	0.067	-9999	-0.41	12	12
SHF	0.01	0.049	-9999	-0.27	15	15
CSNK2A1	0.025	0.029	-9999	-0.49	1	1
GO:0007205	-0.018	0.11	-9999	-0.42	33	33
SOS1	0.017	0.023	-9999	-0.52	1	1
Ras protein signal transduction	0.019	0.077	-9999	-0.26	34	34
PDGF/PDGFRA/SHB	-0.01	0.11	-9999	-0.39	38	38
PDGF/PDGFRA/Caveolin-1	-0.016	0.12	-9999	-0.41	36	36
ITGAV	-0.002	0.1	-9999	-0.48	21	21
ELK1	-0.018	0.1	-9999	-0.36	36	36
PIK3CA	0.016	0.029	-9999	-0.34	3	3
PDGF/PDGFRA/Crk	-0.004	0.1	-9999	-0.38	33	33
JAK-STAT cascade	-0.009	0.1	-9999	-0.38	37	37
cell proliferation	-0.009	0.1	-9999	-0.34	40	40

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.1	0.22	-10000	0	-0.62	48	48
RAD9A	0.018	0	-10000	0	-10000	0	0
AP1	-0.1	0.19	-10000	0	-0.43	107	107
IFNAR2	0.013	0.036	-10000	0	-0.3	6	6
AKT1	-0.053	0.12	-10000	0	-0.26	76	76
ER alpha/Oestrogen	-0.12	0.18	-10000	0	-0.33	199	199
NFX1/SIN3/HDAC complex	0.038	0.048	-10000	0	-0.28	3	3
EGF	-0.14	0.23	-10000	0	-0.42	193	193
SMG5	0.016	0.029	-10000	0	-0.34	3	3
SMG6	0.017	0.023	-10000	0	-0.52	1	1
SP3/HDAC2	0.019	0.041	-10000	0	-0.25	6	6
TERT/c-Abl	-0.089	0.21	-10000	0	-0.58	46	46
SAP18	0.017	0.001	-10000	0	-10000	0	0
MRN complex	0.03	0.045	-10000	0	-0.3	9	9
WT1	-0.1	0.19	-10000	0	-0.35	172	172
WRN	0.012	0.049	-10000	0	-0.34	9	9
SP1	0.016	0.025	-10000	0	-0.53	1	1
SP3	0.017	0.003	-10000	0	-10000	0	0
TERF2IP	0.018	0	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.099	0.17	-10000	0	-0.55	35	35
Mad/Max	0.021	0.023	-10000	0	-10000	0	0
TERT	-0.1	0.23	-10000	0	-0.65	42	42
CCND1	-0.2	0.44	-10000	0	-1.1	89	89
MAX	0.017	0.004	-10000	0	-10000	0	0
RBBP7	0.01	0.051	-10000	0	-0.3	13	13
RBBP4	0.016	0.026	-10000	0	-0.39	2	2
TERF2	0.014	0.036	-10000	0	-0.46	3	3
PTGES3	0.016	0.026	-10000	0	-0.39	2	2
SIN3A	0.017	0.001	-10000	0	-10000	0	0
Telomerase/911	0.026	0.046	-10000	0	-0.35	2	2
CDKN1B	-0.072	0.19	-10000	0	-0.43	84	84
RAD1	0.016	0.033	-10000	0	-0.52	2	2
XRCC5	0.018	0	-10000	0	-10000	0	0
XRCC6	0.017	0.012	-10000	0	-0.25	1	1
SAP30	0.012	0.053	-10000	0	-0.48	6	6
TRF2/PARP2	0.024	0.03	-10000	0	-0.36	3	3
UBE3A	0.015	0.033	-10000	0	-0.52	2	2
JUN	-0.034	0.15	-10000	0	-0.46	57	57
E6	-0.001	0.003	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.011	0.025	-10000	0	-0.38	2	2
FOS	-0.11	0.2	-10000	0	-0.37	171	171
IFN-gamma/IRF1	-0.075	0.16	-10000	0	-0.36	103	103
PARP2	0.017	0.012	-10000	0	-0.25	1	1
BLM	-0.021	0.13	-10000	0	-0.4	48	48
Telomerase	0.025	0.06	-10000	0	-0.34	3	3
IRF1	-0.017	0.12	-10000	0	-0.37	40	40
ESR1	-0.16	0.24	-10000	0	-0.46	199	199
KU/TER	0.026	0.008	-10000	0	-10000	0	0
ATM/TRF2	0.025	0.023	-10000	0	-0.26	3	3
ubiquitin-dependent protein catabolic process	0.043	0.051	-10000	0	-0.35	2	2
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.043	0.052	-10000	0	-0.36	2	2
HDAC1	0.016	0.023	-10000	0	-0.52	1	1
HDAC2	0.008	0.055	-10000	0	-0.3	15	15
ATM	0.001	0.017	0.21	3	-10000	0	3
SMAD3	0.015	0.059	-10000	0	-0.36	11	11
ABL1	0.018	0	-10000	0	-10000	0	0
MXD1	0.014	0.031	-10000	0	-0.25	7	7
MRE11A	0.018	0	-10000	0	-10000	0	0
HUS1	0.016	0.02	-10000	0	-0.25	3	3
RPS6KB1	0.008	0.049	-10000	0	-0.25	18	18
TERT/NF kappa B1/14-3-3	-0.091	0.22	-10000	0	-0.57	62	62
NR2F2	-0.05	0.17	-10000	0	-0.44	79	79
MAPK3	0.019	0.041	-10000	0	-0.37	4	4
MAPK1	0.018	0.044	-10000	0	-0.37	5	5
TGFB1/TGF beta receptor Type II	0.017	0.023	-10000	0	-0.52	1	1
NFKB1	0.017	0.023	-10000	0	-0.52	1	1
HNRNPC	0.018	0	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.001	0.017	0.21	3	-10000	0	3
NBN	0.015	0.035	-10000	0	-0.43	3	3
EGFR	-0.079	0.18	-10000	0	-0.35	139	139
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.15	0.2	-10000	0	-0.42	173	173
MYC	-0.027	0.14	-10000	0	-0.43	52	52
IL2	0.01	0.052	-10000	0	-0.34	10	10
KU	0.026	0.008	-10000	0	-10000	0	0
RAD50	0.011	0.062	-10000	0	-0.52	7	7
HSP90AA1	0.013	0.045	-10000	0	-0.39	6	6
TGFB1	0.017	0.024	-10000	0	-0.52	1	1
TRF2/BLM	-0.002	0.091	-10000	0	-0.35	30	30
FRAP1	0.018	0	-10000	0	-10000	0	0
KU/TERT	-0.08	0.21	-10000	0	-0.6	37	37
SP1/HDAC2	0.019	0.048	-10000	0	-0.25	11	11
PINX1	0.016	0.02	-10000	0	-0.25	3	3
Telomerase/EST1A	-0.1	0.17	-10000	0	-0.55	36	36
Smad3/Myc	-0.003	0.099	-10000	0	-0.31	46	46
911 complex	0.034	0.024	-10000	0	-0.3	2	2
IFNG	-0.092	0.18	-10000	0	-0.33	161	161
Telomerase/PinX1	-0.099	0.17	-10000	0	-0.55	37	37
Telomerase/AKT1/mTOR/p70S6K	-0.008	0.092	-10000	0	-0.47	5	5
SIN3B	0.017	0.012	-10000	0	-0.25	1	1
YWHAE	0.016	0.029	-10000	0	-0.34	3	3
Telomerase/EST1B	-0.1	0.17	-10000	0	-0.55	38	38
response to DNA damage stimulus	0.004	0.005	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.044	0.047	-10000	0	-0.27	11	11
TRF2/WRN	0.02	0.043	-10000	0	-0.35	6	6
Telomerase/hnRNP C1/C2	-0.099	0.17	-10000	0	-0.55	35	35
E2F1	0.005	0.071	-10000	0	-0.37	16	16
ZNFX1	0.007	0.071	-10000	0	-0.42	13	13
PIF1	0.015	0.026	-10000	0	-0.25	5	5
NCL	0.018	0	-10000	0	-10000	0	0
DKC1	0.016	0.02	-10000	0	-0.25	3	3
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.012	0.1	-10000	0	-0.26	56	56
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.014	0.047	-10000	0	-0.52	4	4
STAT1 (dimer)/Cbp/p300	-0.01	0.15	-10000	0	-0.45	28	28
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.015	0.061	-10000	0	-0.35	10	10
antigen processing and presentation of peptide antigen via MHC class I	-0.055	0.1	-10000	0	-0.29	60	60
CaM/Ca2+	-0.007	0.097	-10000	0	-0.32	16	16
RAP1A	0.012	0.057	-10000	0	-0.52	6	6
STAT1 (dimer)/SHP2	-0.027	0.13	-10000	0	-0.35	39	39
AKT1	-0.012	0.11	-10000	0	-0.36	19	19
MAP2K1	-0.024	0.12	-10000	0	-0.34	36	36
MAP3K11	-0.011	0.098	-10000	0	-0.32	18	18
IFNGR1	0.01	0.034	-10000	0	-0.27	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.03	0.14	-10000	0	-0.42	33	33
Rap1/GTP	-0.03	0.07	-10000	0	-0.33	13	13
CRKL/C3G	0.023	0.034	-10000	0	-0.37	4	4
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.009	0.11	-10000	0	-0.27	52	52
CEBPB	-0.01	0.16	-10000	0	-0.44	33	33
STAT3	0.015	0.04	-10000	0	-0.52	3	3
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.001	0.11	-10000	0	-0.67	4	4
STAT1	-0.029	0.13	-10000	0	-0.35	39	39
CALM1	0.018	0	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.086	0.17	-10000	0	-0.33	161	161
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
STAT1 (dimer)/PIAS1	-0.019	0.12	-10000	0	-0.38	28	28
CEBPB/PTGES2/Cbp/p300	-0.043	0.11	-10000	0	-0.38	33	33
mol:Ca2+	-0.014	0.1	-10000	0	-0.26	56	56
MAPK3	-0.016	0.14	-10000	0	-0.46	17	17
STAT1 (dimer)	-0.07	0.15	-10000	0	-0.43	55	55
MAPK1	-0.017	0.14	-10000	0	-0.49	17	17
JAK2	0.007	0.056	-10000	0	-0.34	12	12
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
JAK1	0.008	0.059	-10000	0	-0.54	6	6
CAMK2D	-0.005	0.1	-10000	0	-0.4	29	29
DAPK1	0	0.14	-10000	0	-0.48	23	23
SMAD7	0.004	0.073	-10000	0	-0.18	21	21
CBL/CRKL/C3G	0.005	0.095	-10000	0	-0.35	11	11
PI3K	-0.022	0.11	-10000	0	-0.36	21	21
IFNG	-0.086	0.17	-10000	0	-0.33	161	161
apoptosis	-0.007	0.12	0.27	2	-0.34	31	33
CAMK2G	0.017	0.017	-10000	0	-0.25	2	2
STAT3 (dimer)	0.015	0.04	-10000	0	-0.52	3	3
CAMK2A	0.017	0.023	-10000	0	-0.52	1	1
CAMK2B	-0.078	0.18	-10000	0	-0.36	133	133
FRAP1	-0.004	0.1	-10000	0	-0.36	14	14
PRKCD	-0.01	0.11	-10000	0	-0.36	18	18
RAP1B	0.013	0.044	-10000	0	-0.32	8	8
negative regulation of cell growth	-0.055	0.1	-10000	0	-0.29	60	60
PTPN2	0.016	0.024	-10000	0	-0.25	4	4
EP300	0.014	0.047	-10000	0	-0.52	4	4
IRF1	-0.007	0.15	-10000	0	-0.47	35	35
STAT1 (dimer)/PIASy	-0.024	0.13	-10000	0	-0.41	25	25
SOCS1	0.01	0.064	-10000	0	-1.4	1	1
mol:GDP	0.003	0.091	-10000	0	-0.33	11	11
CASP1	-0.017	0.12	-10000	0	-0.28	68	68
PTGES2	0.017	0.012	-10000	0	-0.25	1	1
IRF9	0.017	0.085	-10000	0	-0.31	20	20
mol:PI-3-4-5-P3	-0.048	0.089	-10000	0	-0.34	23	23
RAP1/GDP	-0.03	0.071	-10000	0	-0.33	14	14
CBL	-0.01	0.097	-10000	0	-0.31	19	19
MAP3K1	-0.033	0.12	-10000	0	-0.32	54	54
PIAS1	0.017	0.012	-10000	0	-0.25	1	1
PIAS4	0.012	0.05	-10000	0	-0.43	6	6
antigen processing and presentation of peptide antigen via MHC class II	-0.055	0.1	-10000	0	-0.29	60	60
PTPN11	-0.019	0.1	-10000	0	-0.26	56	56
CREBBP	0.016	0.033	-10000	0	-0.52	2	2
RAPGEF1	0.018	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.01	0.048	-9999	-0.25	17	17
ELF1	-0.012	0.12	-9999	-0.37	44	44
CCNA2	-0.026	0.13	-9999	-0.39	57	57
PIK3CA	0.016	0.029	-9999	-0.34	3	3
JAK3	0.018	0	-9999	-10000	0	0
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
JAK1	0.012	0.057	-9999	-0.52	6	6
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.01	0.14	-9999	-0.43	27	27
SHC1	0.018	0.023	-9999	-0.52	1	1
SP1	0.015	0.07	-9999	-0.36	16	16
IL2RA	-0.035	0.2	-9999	-0.68	43	43
IL2RB	-0.016	0.12	-9999	-0.43	40	40
SOS1	0.017	0.023	-9999	-0.52	1	1
IL2RG	-0.001	0.078	-9999	-0.28	35	35
G1/S transition of mitotic cell cycle	-0.026	0.2	-9999	-0.57	47	47
PTPN11	0.018	0.023	-9999	-0.52	1	1
CCND2	0.009	0.14	-9999	-0.77	16	16
LCK	-0.073	0.18	-9999	-0.4	117	117
GRB2	0.016	0.024	-9999	-0.25	4	4
IL2	0.012	0.051	-9999	-0.33	10	10
CDK6	-0.019	0.1	-9999	-0.29	63	63
CCND3	0.021	0.12	-9999	-0.45	13	13

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.019	0.071	0.24	15	-0.24	23	38
DAPP1	-0.038	0.14	-10000	0	-0.43	42	42
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.051	0.22	-10000	0	-0.53	65	65
mol:DAG	0.001	0.1	0.19	9	-0.23	49	58
HRAS	0.012	0.051	-10000	0	-0.41	7	7
RAP1A	0.012	0.057	-10000	0	-0.52	6	6
ARF5/GDP	-0.016	0.11	-10000	0	-0.32	30	30
PLCG2	-0.017	0.11	-10000	0	-0.32	55	55
PLCG1	0.016	0.026	-10000	0	-0.39	2	2
ARF5	0.015	0.04	-10000	0	-0.52	3	3
mol:GTP	-0.006	0.068	0.22	15	-0.25	25	40
ARF1/GTP	-0.006	0.067	0.22	15	-0.24	25	40
RHOA	0.005	0.08	-10000	0	-0.52	12	12
YES1	0.007	0.07	-10000	0	-0.43	12	12
RAP1A/GTP	0.015	0.069	0.22	15	-0.25	25	40
ADAP1	-0.006	0.065	0.21	15	-0.24	25	40
ARAP3	-0.006	0.067	0.22	15	-0.25	25	40
INPPL1	0.012	0.055	-10000	0	-0.44	7	7
PREX1	-0.089	0.2	-10000	0	-0.44	124	124
ARHGEF6	-0.019	0.13	-10000	0	-0.41	45	45
ARHGEF7	0.016	0.02	-10000	0	-0.25	3	3
ARF1	0.017	0.023	-10000	0	-0.52	1	1
NRAS	0.005	0.076	-10000	0	-0.4	16	16
FYN	0.008	0.067	-10000	0	-0.41	12	12
ARF6	0.016	0.033	-10000	0	-0.52	2	2
FGR	0.017	0.017	-10000	0	-0.25	2	2
mol:Ca2+	0.006	0.054	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.006	0.073	-10000	0	-0.44	13	13
ZAP70	0.005	0.06	-10000	0	-0.26	24	24
mol:IP3	0.004	0.073	-10000	0	-0.18	24	24
LYN	0.014	0.031	-10000	0	-0.25	7	7
ARF1/GDP	-0.015	0.1	-10000	0	-0.32	28	28
RhoA/GDP	0.003	0.099	0.23	6	-0.34	25	31
PDK1/Src/Hsp90	0.031	0.039	-10000	0	-0.3	6	6
BLNK	-0.012	0.12	-10000	0	-0.51	30	30
actin cytoskeleton reorganization	-0.006	0.12	0.23	6	-0.41	23	29
SRC	0.015	0.035	-10000	0	-0.43	3	3
PLEKHA2	0.014	0.043	-10000	0	-0.31	8	8
RAC1	0.018	0	-10000	0	-10000	0	0
PTEN	-0.003	0.096	-10000	0	-0.5	19	19
HSP90AA1	0.013	0.045	-10000	0	-0.39	6	6
ARF6/GTP	0.019	0.069	0.24	14	-0.24	21	35
RhoA/GTP	0.015	0.082	0.22	14	-0.26	32	46
Src family/SYK family/BLNK-LAT	-0.032	0.17	-10000	0	-0.47	47	47
BLK	-0.019	0.1	-10000	0	-0.29	63	63
PDPK1	0.016	0.026	-10000	0	-0.39	2	2
CYTH1	-0.006	0.065	0.21	15	-0.24	25	40
HCK	-0.005	0.11	-10000	0	-0.47	25	25
CYTH3	-0.006	0.065	0.21	15	-0.24	25	40
CYTH2	-0.006	0.065	0.21	15	-0.24	25	40
KRAS	0.009	0.065	-10000	0	-0.44	10	10
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.025	0.052	0.18	12	-0.22	5	17
SGK1	-0.004	0.047	0.18	13	-0.21	6	19
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.025	0.11	-10000	0	-0.29	41	41
SOS1	0.017	0.023	-10000	0	-0.52	1	1
SYK	-0.023	0.14	-10000	0	-0.48	43	43
ARF6/GDP	0.005	0.085	0.24	6	-0.3	20	26
mol:PI-3-4-5-P3	-0.004	0.074	0.25	19	-0.25	25	44
ARAP3/RAP1A/GTP	0.014	0.07	0.22	15	-0.25	25	40
VAV1	-0.014	0.12	-10000	0	-0.39	42	42
mol:PI-3-4-P2	0.008	0.039	-10000	0	-0.32	7	7
RAS family/GTP/PI3K Class I	0.022	0.069	-10000	0	-0.25	25	25
PLEKHA1	0.012	0.052	-10000	0	-0.32	12	12
Rac1/GDP	-0.014	0.1	-10000	0	-0.32	28	28
LAT	0.002	0.068	-10000	0	-0.27	29	29
Rac1/GTP	-0.03	0.14	-10000	0	-0.4	42	42
ITK	-0.008	0.1	0.22	14	-0.25	57	71
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.008	0.13	0.22	8	-0.32	50	58
LCK	-0.074	0.18	-10000	0	-0.4	117	117
BTK	0.007	0.091	0.22	14	-0.27	37	51

×

Insulin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.048	0.1	-9999	-0.26	88	88
TC10/GTP	-0.022	0.063	-9999	-0.23	39	39
Insulin Receptor/Insulin/IRS1/Shp2	0.005	0.11	-9999	-0.29	63	63
HRAS	0.012	0.051	-9999	-0.41	7	7
APS homodimer	0	0	-9999	-10000	0	0
GRB14	-0.16	0.21	-9999	-0.36	247	247
FOXO3	-0.021	0.065	-9999	-0.71	4	4
AKT1	-0.068	0.14	-9999	-0.37	44	44
INSR	0.015	0.038	-9999	-0.38	4	4
Insulin Receptor/Insulin	0.036	0.079	-9999	-0.49	4	4
mol:GTP	0	0	-9999	-10000	0	0
GRB10	-0.003	0.097	-9999	-0.43	24	24
SORBS1	-0.032	0.14	-9999	-0.39	65	65
CRK	0.016	0.033	-9999	-0.52	2	2
PTPN1	0.023	0.075	-9999	-0.48	4	4
CAV1	-0.012	0.11	-9999	-0.27	69	69
CBL/APS/CAP/Crk-II/C3G	0.014	0.078	-9999	-0.25	35	35
Insulin Receptor/Insulin/IRS1/NCK2	0.004	0.11	-9999	-0.29	62	62
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.011	0.11	-9999	-0.25	80	80
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.013	0.09	-9999	-0.46	6	6
RPS6KB1	-0.06	0.13	-9999	-0.33	50	50
PARD6A	0.004	0.081	-9999	-0.44	16	16
CBL	0.017	0.012	-9999	-0.25	1	1
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	-0.014	0.11	-9999	-0.78	11	11
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.082	0.11	-9999	-0.33	51	51
HRAS/GTP	-0.028	0.073	-9999	-0.33	7	7
Insulin Receptor	0.015	0.037	-9999	-0.38	4	4
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.014	0.1	-9999	-0.26	63	63
PRKCI	-0.033	0.1	-9999	-0.52	21	21
Insulin Receptor/Insulin/GRB14/PDK1	-0.098	0.12	-9999	-0.37	48	48
SHC1	0.017	0.023	-9999	-0.52	1	1
negative regulation of MAPKKK cascade	0.009	0.12	-9999	-0.67	12	12
PI3K	-0.005	0.11	-9999	-0.26	80	80
NCK2	0.015	0.026	-9999	-0.25	5	5
RHOQ	0.012	0.053	-9999	-0.48	6	6
mol:H2O2	-0.002	0.008	-9999	-10000	0	0
HRAS/GDP	0.009	0.036	-9999	-0.29	7	7
AKT2	-0.065	0.13	-9999	-0.36	42	42
PRKCZ	-0.028	0.074	-9999	-0.53	9	9
SH2B2	0	0	-9999	-10000	0	0
SHC/SHIP	-0.002	0.093	-9999	-0.25	63	63
F2RL2	-0.074	0.19	-9999	-0.44	105	105
TRIP10	0.013	0.048	-9999	-0.47	5	5
Insulin Receptor/Insulin/Shc	0.032	0.029	-9999	-0.27	4	4
TC10/GTP/CIP4/Exocyst	0.018	0.045	-9999	-0.31	9	9
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.05	0.036	-9999	-0.38	2	2
RAPGEF1	0.018	0	-9999	-10000	0	0
RASA1	0.004	0.078	-9999	-0.42	16	16
NCK1	0.011	0.045	-9999	-0.28	12	12
CBL/APS/CAP/Crk-II	0.005	0.082	-9999	-0.28	35	35
TC10/GDP	0.009	0.039	-9999	-0.34	6	6
Insulin Receptor/Insulin/SHC/GRB10	0.032	0.064	-9999	-0.27	20	20
INPP5D	-0.014	0.096	-9999	-0.27	62	62
SOS1	0.017	0.023	-9999	-0.52	1	1
SGK1	-0.01	0.012	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.017	0.023	-9999	-0.52	1	1
IRS1	-0.048	0.17	-9999	-0.49	68	68
p62DOK/RasGAP	0.009	0.12	-9999	-0.68	12	12
INS	0.017	0.025	-9999	-0.52	1	1
mol:PI-3-4-P2	-0.013	0.096	-9999	-0.27	62	62
GRB2	0.016	0.024	-9999	-0.25	4	4
EIF4EBP1	-0.067	0.13	-9999	-0.34	57	57
PTPRA	0.017	0.028	-9999	-0.4	2	2
PIK3CA	0.016	0.029	-9999	-0.34	3	3
TC10/GTP/CIP4	0.018	0.045	-9999	-0.31	9	9
PDPK1	0.016	0.026	-9999	-0.39	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.009	0.095	-9999	-0.4	6	6
Insulin Receptor/Insulin/IRS1	-0.006	0.11	-9999	-0.29	62	62
Insulin Receptor/Insulin/IRS3	0.024	0.034	-9999	-0.37	3	3
Par3/Par6	-0.02	0.13	-9999	-0.29	86	86

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.011	0.088	-10000	0	-0.29	23	23
adherens junction organization	-0.013	0.11	-10000	0	-0.25	78	78
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.019	0.11	-10000	0	-0.34	21	21
FMN1	-0.008	0.1	-10000	0	-0.24	78	78
mol:IP3	0.006	0.081	-10000	0	-0.25	23	23
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.008	0.11	-10000	0	-0.25	78	78
CTNNB1	0.002	0.09	-10000	0	-0.45	19	19
AKT1	0.007	0.092	-10000	0	-0.33	11	11
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.018	0.15	-10000	0	-0.38	76	76
CTNND1	0.016	0.029	-10000	0	-0.34	3	3
mol:PI-4-5-P2	0	0.1	-10000	0	-0.33	10	10
VASP	-0.007	0.11	-10000	0	-0.32	20	20
ZYX	-0.006	0.11	-10000	0	-0.36	13	13
JUB	-0.023	0.13	-10000	0	-0.39	21	21
EGFR(dimer)	-0.043	0.13	-10000	0	-0.35	32	32
E-cadherin/beta catenin-gamma catenin	-0.019	0.12	-10000	0	-0.3	78	78
mol:PI-3-4-5-P3	0.003	0.092	-10000	0	-0.26	28	28
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
PI3K	0.004	0.093	-10000	0	-0.26	28	28
FYN	0.015	0.085	-10000	0	-0.3	15	15
mol:Ca2+	0.006	0.08	-10000	0	-0.24	23	23
JUP	0.012	0.056	-10000	0	-0.42	8	8
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
mol:DAG	0.006	0.081	-10000	0	-0.25	23	23
CDH1	-0.049	0.17	-10000	0	-0.48	70	70
RhoA/GDP	-0.025	0.12	-10000	0	-0.35	28	28
establishment of polarity of embryonic epithelium	-0.006	0.11	-10000	0	-0.32	20	20
SRC	0.015	0.035	-10000	0	-0.43	3	3
RAC1	0.018	0	-10000	0	-10000	0	0
RHOA	0.005	0.08	-10000	0	-0.52	12	12
EGFR	-0.079	0.18	-10000	0	-0.35	139	139
CASR	0.012	0.078	-10000	0	-0.31	7	7
RhoA/GTP	0.008	0.086	-10000	0	-0.32	11	11
AKT2	0.009	0.087	-10000	0	-0.32	7	7
actin cable formation	-0.007	0.1	-10000	0	-0.31	20	20
apoptosis	-0.006	0.089	0.26	26	-10000	0	26
CTNNA1	0.017	0.024	-10000	0	-0.52	1	1
mol:GDP	-0.03	0.12	-10000	0	-0.36	22	22
PIP5K1A	-0.001	0.1	-10000	0	-0.34	10	10
PLCG1	0.006	0.082	-10000	0	-0.25	23	23
Rac1/GTP	-0.034	0.12	-10000	0	-0.32	31	31
homophilic cell adhesion	0	0.003	-10000	0	-10000	0	0

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	0.019	0.05	-10000	0	-0.37	8	8
Necdin/E2F1	-0.027	0.14	-10000	0	-0.38	62	62
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.01	0.11	-10000	0	-0.27	78	78
NGF (dimer)/p75(NTR)/BEX1	-0.016	0.075	-10000	0	-0.29	12	12
NT-4/5 (dimer)/p75(NTR)	0.004	0.045	-10000	0	-0.2	23	23
IKBKB	0.012	0.047	-10000	0	-0.31	10	10
AKT1	0.01	0.072	-10000	0	-0.25	30	30
IKBKG	0.018	0	-10000	0	-10000	0	0
BDNF	-0.016	0.091	-10000	0	-0.26	64	64
MGDIs/NGR/p75(NTR)/LINGO1	-0.003	0.086	-10000	0	-0.31	22	22
FURIN	0.004	0.076	-10000	0	-0.37	19	19
proBDNF (dimer)/p75(NTR)/Sortilin	0.004	0.075	-10000	0	-0.33	11	11
LINGO1	-0.019	0.095	-10000	0	-0.26	69	69
Sortilin/TRAF6/NRIF	-0.017	0.056	-10000	0	-0.33	5	5
proBDNF (dimer)	-0.016	0.09	-10000	0	-0.26	64	64
NTRK1	0.01	0.053	-10000	0	-0.32	12	12
RTN4R	0.001	0.087	-10000	0	-0.41	21	21
neuron apoptosis	0.003	0.1	-10000	0	-0.43	9	9
IRAK1	0.015	0.029	-10000	0	-0.25	6	6
SHC1	0.013	0.04	-10000	0	-0.31	4	4
ARHGDIA	0.016	0.029	-10000	0	-0.34	3	3
RhoA/GTP	0.004	0.058	-10000	0	-0.38	12	12
Gamma Secretase	0.033	0.069	-10000	0	-0.25	25	25
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.001	0.095	-10000	0	-0.3	43	43
MAGEH1	-0.019	0.14	-10000	0	-0.52	36	36
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.013	0.11	-10000	0	-0.3	65	65
Mammalian IAPs/DIABLO	-0.024	0.11	-10000	0	-0.28	76	76
proNGF (dimer)	0	0	-10000	0	-10000	0	0
MAGED1	-0.008	0.11	-10000	0	-0.48	27	27
APP	-0.029	0.14	-10000	0	-0.43	56	56
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
ZNF274	0.013	0.044	-10000	0	-0.32	8	8
RhoA/GDP/RHOGDI	0.017	0.057	-10000	0	-0.27	16	16
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	0.006	0.054	0.15	3	-0.26	10	13
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.026	0.04	-10000	0	-0.23	9	9
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.016	0.041	-10000	0	-0.31	4	4
NCSTN	0.017	0.023	-10000	0	-0.52	1	1
mol:GTP	-0.016	0.089	-10000	0	-0.31	31	31
PSENEN	0.017	0.012	-10000	0	-0.25	1	1
mol:ceramide	0.014	0.056	-10000	0	-0.29	12	12
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.022	0.049	-10000	0	-0.19	22	22
p75(NTR)/beta APP	-0.017	0.11	-10000	0	-0.37	39	39
BEX1	-0.039	0.11	-10000	0	-0.26	108	108
mol:GDP	0.002	0.037	-10000	0	-0.16	23	23
NGF (dimer)	-0.038	0.13	-10000	0	-0.29	101	101
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.009	0.081	-10000	0	-0.28	23	23
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
RAC1/GTP	0.015	0.032	-10000	0	-0.27	3	3
MYD88	0.013	0.048	-10000	0	-0.47	5	5
CHUK	0.005	0.081	-10000	0	-0.5	13	13
NGF (dimer)/p75(NTR)/PKA	-0.016	0.09	-10000	0	-0.31	31	31
RHOB	-0.041	0.17	-10000	0	-0.52	58	58
RHOA	0.005	0.08	-10000	0	-0.52	12	12
MAGE-G1/E2F1	0.018	0.051	-10000	0	-0.37	7	7
NT3 (dimer)	-0.021	0.11	-10000	0	-0.28	68	68
TP53	-0.001	0.098	-10000	0	-0.26	49	49
PRDM4	0.017	0.049	-10000	0	-0.28	10	10
BDNF (dimer)	-0.12	0.2	-10000	0	-0.37	173	173
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
SORT1	0.009	0.065	-10000	0	-0.44	10	10
activation of caspase activity	-0.013	0.11	-10000	0	-0.27	78	78
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.022	0.052	-10000	0	-0.28	11	11
RHOC	0.015	0.04	-10000	0	-0.52	3	3
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	0	0.095	-10000	0	-0.29	22	22
DIABLO	0.018	0	-10000	0	-10000	0	0
SMPD2	0.014	0.056	-10000	0	-0.3	12	12
APH1B	0.001	0.093	-10000	0	-0.51	17	17
APH1A	0.003	0.067	-10000	0	-0.29	25	25
proNGF (dimer)/p75(NTR)/Sortilin	0.011	0.055	-10000	0	-0.31	10	10
PSEN1	0.013	0.052	-10000	0	-0.52	5	5
APAF-1/Pro-Caspase 9	0.022	0.041	-10000	0	-0.37	5	5
NT3 (dimer)/p75(NTR)	-0.009	0.09	-10000	0	-0.4	13	13
MAPK8	0.014	0.08	-10000	0	-0.28	11	11
MAPK9	0.005	0.096	-10000	0	-0.31	20	20
APAF1	0.012	0.051	-10000	0	-0.41	7	7
NTF3	-0.021	0.11	-10000	0	-0.28	68	68
NTF4	0	0	-10000	0	-10000	0	0
NDN	-0.044	0.17	-10000	0	-0.49	65	65
RAC1/GDP	0.013	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.028	0.12	-10000	0	-0.25	96	96
p75 CTF/Sortilin/TRAF6/NRIF	0.036	0.048	-10000	0	-0.27	10	10
RhoA-B-C/GTP	-0.016	0.089	-10000	0	-0.31	31	31
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.021	0.07	-10000	0	-0.26	14	14
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.015	0.071	-10000	0	-0.29	12	12
PRKACB	-0.036	0.14	-10000	0	-0.34	79	79
proBDNF (dimer)/p75 ECD	0.002	0.064	-10000	0	-0.34	2	2
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.085	0.19	-10000	0	-0.41	128	128
BIRC2	0.016	0.02	-10000	0	-0.25	3	3
neuron projection morphogenesis	-0.033	0.11	0.2	2	-0.3	50	52
BAD	0.008	0.091	-10000	0	-0.29	17	17
RIPK2	0.013	0.04	-10000	0	-0.28	9	9
NGFR	0.004	0.065	-10000	0	-0.29	23	23
CYCS	0.01	0.074	-10000	0	-0.25	34	34
ADAM17	0.016	0.024	-10000	0	-0.25	4	4
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.024	0.044	-10000	0	-0.27	6	6
BCL2L11	0.008	0.091	-10000	0	-0.29	17	17
BDNF (dimer)/p75(NTR)	-0.006	0.075	-10000	0	-0.4	4	4
PI3K	0.011	0.072	-10000	0	-0.28	25	25
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.022	0.05	-10000	0	-0.28	10	10
NDNL2	0.018	0	-10000	0	-10000	0	0
YWHAE	0.016	0.029	-10000	0	-0.34	3	3
PRKCI	0.002	0.085	-10000	0	-0.43	18	18
NGF (dimer)/p75(NTR)	0.004	0.045	-10000	0	-0.2	23	23
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.008	0.08	-10000	0	-0.28	33	33
TRAF6	0.017	0.023	-10000	0	-0.52	1	1
RAC1	0.018	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
PLG	0.016	0.033	-10000	0	-0.52	2	2
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	0.005	0.07	-10000	0	-0.28	18	18
SQSTM1	0.012	0.053	-10000	0	-0.48	6	6
NGFRAP1	-0.055	0.18	-10000	0	-0.52	72	72
CASP3	0.01	0.087	-10000	0	-0.27	17	17
E2F1	0.006	0.07	-10000	0	-0.37	16	16
CASP9	0.017	0.023	-10000	0	-0.52	1	1
IKK complex	-0.013	0.047	-10000	0	-0.34	3	3
NGF (dimer)/TRKA	0.008	0.037	-10000	0	-0.22	12	12
MMP7	-0.095	0.21	-10000	0	-0.44	129	129
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.028	0.054	-10000	0	-0.25	13	13
MMP3	-0.13	0.22	-10000	0	-0.42	177	177
APAF-1/Caspase 9	-0.046	0.077	-10000	0	-0.31	10	10

×

Ceramide signaling pathway

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
SPHK2	0.01	0.074	-10000	0	-0.37	18	18
MAP4K4	-0.003	0.11	-10000	0	-0.45	12	12
BAG4	0.002	0.07	-10000	0	-0.28	28	28
PKC zeta/ceramide	-0.025	0.04	0.13	8	-0.12	1	9
NFKBIA	0.014	0.042	-10000	0	-0.45	4	4
BIRC3	-0.085	0.19	-10000	0	-0.41	128	128
BAX	-0.003	0.022	-10000	0	-10000	0	0
RIPK1	0.017	0.023	-10000	0	-0.52	1	1
AKT1	0.017	0.051	-10000	0	-0.34	9	9
BAD	-0.018	0.041	0.14	10	-0.18	1	11
SMPD1	0.008	0.06	-10000	0	-0.24	19	19
RB1	-0.028	0.07	0.15	8	-0.32	20	28
FADD/Caspase 8	0.007	0.1	-10000	0	-0.43	11	11
MAP2K4	-0.043	0.092	0.15	5	-0.28	55	60
NSMAF	0.009	0.065	-10000	0	-0.44	10	10
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.01	0.04	0.15	4	-0.18	1	5
EGF	-0.14	0.23	-10000	0	-0.42	193	193
mol:ceramide	-0.027	0.044	0.14	11	-0.12	1	12
MADD	0.018	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.028	0.13	-10000	0	-0.38	56	56
ASAH1	-0.036	0.15	-10000	0	-0.42	65	65
negative regulation of cell cycle	-0.027	0.069	0.15	8	-0.31	20	28
cell proliferation	-0.036	0.097	-10000	0	-0.23	83	83
BID	-0.013	0.12	-10000	0	-0.55	17	17
MAP3K1	-0.041	0.084	0.15	7	-0.3	38	45
EIF2A	-0.013	0.059	0.15	1	-0.26	15	16
TRADD	0.016	0.026	-10000	0	-0.39	2	2
CRADD	0.01	0.063	-10000	0	-0.49	8	8
MAPK3	0.002	0.039	0.16	1	-0.19	1	2
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.001	0.04	-10000	0	-0.19	1	1
Cathepsin D/ceramide	-0.022	0.055	0.14	7	-0.22	12	19
FADD	-0.006	0.11	-10000	0	-0.38	19	19
KSR1	-0.017	0.042	0.15	8	-0.2	1	9
MAPK8	-0.03	0.069	0.14	5	-0.2	51	56
PRKRA	-0.017	0.042	0.15	8	-10000	0	8
PDGFA	-0.003	0.099	-10000	0	-0.44	24	24
TRAF2	0.014	0.042	-10000	0	-0.45	4	4
IGF1	-0.1	0.2	-10000	0	-0.41	146	146
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.026	0.044	0.14	11	-0.12	1	12
CTSD	0.002	0.075	-10000	0	-0.32	24	24
regulation of nitric oxide biosynthetic process	0.026	0.017	-10000	0	-0.37	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.035	0.11	-10000	0	-0.25	81	81
PRKCD	0.014	0.042	-10000	0	-0.45	4	4
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.028	0.13	-10000	0	-0.38	56	56
RelA/NF kappa B1	0.026	0.017	-10000	0	-0.37	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0	0.091	-10000	0	-0.44	20	20
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.005	0.11	-10000	0	-0.45	13	13
TNFR1A/BAG4/TNF-alpha	0.012	0.074	-10000	0	-0.31	18	18
mol:Sphingosine-1-phosphate	0.01	0.074	-10000	0	-0.37	18	18
MAP2K1	-0.002	0.039	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.018	0	-10000	0	-10000	0	0
CYCS	0.027	0.065	0.16	76	-10000	0	76
TNFRSF1A	0.016	0.033	-10000	0	-0.52	2	2
NFKB1	0.017	0.023	-10000	0	-0.52	1	1
TNFR1A/BAG4	0.014	0.054	-10000	0	-0.37	5	5
EIF2AK2	-0.02	0.061	0.15	7	-0.26	18	25
TNF-alpha/TNFR1A/FAN	0.016	0.073	-10000	0	-0.31	21	21
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.02	0.062	-10000	0	-0.3	2	2
MAP2K2	-0.003	0.043	-10000	0	-0.27	3	3
SMPD3	0.005	0.072	-10000	0	-0.26	20	20
TNF	-0.004	0.094	-10000	0	-0.36	31	31
PKC zeta/PAR4	0.001	0.065	-10000	0	-0.32	20	20
mol:PHOSPHOCHOLINE	0.055	0.1	0.22	129	-10000	0	129
NF kappa B1/RelA/I kappa B alpha	0.03	0.055	-10000	0	-0.25	18	18
AIFM1	0.027	0.065	0.16	76	-10000	0	76
BCL2	-0.11	0.22	-10000	0	-0.47	144	144

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.01	0.079	-9999	-0.29	23	23
STMN1	0.002	0.088	-9999	-0.38	22	22
Aurora B/RasGAP/Survivin	-0.011	0.12	-9999	-0.34	53	53
Chromosomal passenger complex/Cul3 protein complex	-0.052	0.14	-9999	-0.35	57	57
BIRC5	-0.038	0.16	-9999	-0.43	67	67
DES	-0.026	0.13	-9999	-0.68	16	16
Aurora C/Aurora B/INCENP	0.015	0.062	-9999	-0.29	14	14
Aurora B/TACC1	-0.005	0.088	-9999	-0.32	32	32
Aurora B/PP2A	0.019	0.042	-9999	-0.39	3	3
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.011	0.033	-9999	-0.21	9	9
mitotic metaphase/anaphase transition	0	0.005	-9999	-10000	0	0
NDC80	-0.014	0.12	-9999	-0.4	39	39
Cul3 protein complex	-0.048	0.14	-9999	-0.33	93	93
KIF2C	-0.061	0.24	-9999	-0.65	59	59
PEBP1	0.013	0.047	-9999	-0.53	4	4
KIF20A	-0.027	0.14	-9999	-0.46	49	49
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.011	0.07	-9999	-0.38	13	13
SEPT1	0.008	0.052	-9999	-0.27	17	17
SMC2	0.003	0.077	-9999	-0.36	20	20
SMC4	0.014	0.04	-9999	-0.34	6	6
NSUN2/NPM1/Nucleolin	0.015	0.082	-9999	-0.87	3	3
PSMA3	0.017	0.012	-9999	-0.25	1	1
G2/M transition of mitotic cell cycle	0	0.003	-9999	-10000	0	0
H3F3B	0.013	0.04	-9999	-0.33	5	5
AURKB	0.009	0.058	-9999	-0.32	14	14
AURKC	0.008	0.053	-9999	-0.27	18	18
CDCA8	-0.016	0.12	-9999	-0.4	42	42
cytokinesis	-0.049	0.26	-9999	-0.74	49	49
Aurora B/Septin1	-0.036	0.23	-9999	-0.7	45	45
AURKA	-0.012	0.11	-9999	-0.41	36	36
INCENP	0.001	0.082	-9999	-0.37	22	22
KLHL13	-0.095	0.2	-9999	-0.39	146	146
BUB1	-0.052	0.17	-9999	-0.44	81	81
hSgo1/Aurora B/Survivin	-0.016	0.14	-9999	-0.38	52	52
EVI5	0.013	0.047	-9999	-0.52	4	4
RhoA/GTP	-0.045	0.24	-9999	-0.65	57	57
SGOL1	-0.01	0.11	-9999	-0.38	37	37
CENPA	-0.041	0.21	-9999	-0.6	50	50
NCAPG	0	0	-9999	-10000	0	0
Aurora B/HC8 Proteasome	0.02	0.041	-9999	-0.39	3	3
NCAPD2	0.012	0.04	-9999	-0.25	12	12
Aurora B/PP1-gamma	0.018	0.05	-9999	-0.38	6	6
RHOA	0.005	0.08	-9999	-0.52	12	12
NCAPH	-0.008	0.11	-9999	-0.46	29	29
NPM1	0.012	0.052	-9999	-0.6	3	3
RASA1	0.004	0.078	-9999	-0.42	16	16
KLHL9	-0.001	0.096	-9999	-0.49	19	19
mitotic prometaphase	-0.001	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.041	-9999	-0.38	3	3
PPP1CC	0.015	0.04	-9999	-0.52	3	3
Centraspindlin	-0.053	0.27	-9999	-0.69	60	60
RhoA/GDP	0.004	0.058	-9999	-0.38	12	12
NSUN2	0.012	0.054	-9999	-0.6	3	3
MYLK	0.003	0.07	-9999	-0.33	20	20
KIF23	-0.024	0.14	-9999	-0.45	47	47
VIM	-0.01	0.11	-9999	-0.38	34	34
RACGAP1	-0.004	0.1	-9999	-0.5	22	22
mitosis	0	0	-9999	-10000	0	0
NCL	0.013	0.052	-9999	-0.6	3	3
Chromosomal passenger complex	-0.045	0.22	-9999	-0.59	54	54
Chromosomal passenger complex/EVI5	-0.012	0.15	-9999	-0.36	62	62
TACC1	-0.022	0.13	-9999	-0.41	49	49
PPP2R5D	0.016	0.02	-9999	-0.25	3	3
CUL3	0.01	0.06	-9999	-0.43	9	9
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.003	0.062	-9999	-1.2	1	1
VDR	-0.003	0.1	-9999	-0.51	21	21
FAM120B	0.016	0.033	-9999	-0.52	2	2
RXRs/LXRs/DNA/9cRA	0.012	0.13	-9999	-0.41	22	22
RXRs/LXRs/DNA/Oxysterols	-0.001	0.18	-9999	-0.44	69	69
MED1	0	0.067	-9999	-0.25	34	34
mol:9cRA	-0.001	0.021	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.003	0.11	-9999	-0.43	16	16
RXRs/NUR77	0.031	0.076	-9999	-0.28	19	19
RXRs/PPAR	0.008	0.093	-9999	-0.34	17	17
NCOR2	0.018	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.075	-9999	-0.37	21	21
RARs/VDR/DNA/Vit D3	0.004	0.095	-9999	-0.27	47	47
RARA	0.011	0.057	-9999	-0.4	9	9
NCOA1	0.012	0.057	-9999	-0.52	6	6
VDR/VDR/DNA	-0.003	0.1	-9999	-0.51	21	21
RARs/RARs/DNA/9cRA	0.005	0.077	-9999	-0.27	29	29
RARG	0.017	0.023	-9999	-0.52	1	1
RPS6KB1	0.004	0.055	-9999	-0.24	19	19
RARs/THRs/DNA/SMRT	0	0.1	-9999	-0.27	57	57
THRA	-0.01	0.11	-9999	-0.38	37	37
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.002	0.075	-9999	-0.37	21	21
RXRs/PPAR/9cRA/PGJ2/DNA	0.022	0.084	-9999	-0.29	18	18
NR1H4	0.015	0.031	-9999	-0.32	4	4
RXRs/LXRs/DNA	0.037	0.11	-9999	-0.42	10	10
NR1H2	0.018	0.017	-9999	-10000	0	0
NR1H3	0.008	0.07	-9999	-0.44	11	11
RXRs/VDR/DNA/Vit D3	0.021	0.088	-9999	-0.27	37	37
NR4A1	0.01	0.049	-9999	-0.27	15	15
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.016	0.063	-9999	-0.26	9	9
RXRG	0.004	0.084	-9999	-0.47	15	15
RXR alpha/CCPG	0.023	0.041	-9999	-0.38	5	5
RXRA	0.014	0.045	-9999	-0.54	3	3
RXRB	0.014	0.045	-9999	-0.52	3	3
THRB	-0.001	0.097	-9999	-0.48	20	20
PPARG	-0.036	0.14	-9999	-0.33	81	81
PPARD	0.017	0.017	-9999	-0.25	2	2
TNF	-0.01	0.23	-9999	-0.8	28	28
mol:Oxysterols	0	0.018	-9999	-10000	0	0
cholesterol transport	0	0.18	-9999	-0.43	69	69
PPARA	0.012	0.047	-9999	-0.31	10	10
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.025	0.13	-9999	-0.36	60	60
RXRs/NUR77/BCL2	-0.04	0.12	-9999	-0.24	130	130
SREBF1	-0.052	0.33	-9999	-1	51	51
RXRs/RXRs/DNA/9cRA	0.022	0.084	-9999	-0.29	18	18
ABCA1	-0.01	0.24	-9999	-0.83	29	29
RARs/THRs	0.001	0.12	-9999	-0.29	57	57
RXRs/FXR	0.034	0.074	-9999	-0.28	19	19
BCL2	-0.11	0.22	-9999	-0.47	144	144

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.009	0.027	-9999	-0.17	12	12
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.007	0.062	-9999	-0.4	3	3
STXBP1	0.017	0.017	-9999	-0.25	2	2
ACh/CHRNA1	0.008	0.046	-9999	-0.34	7	7
RAB3GAP2/RIMS1/UNC13B	0.019	0.054	-9999	-0.32	4	4
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.003	0.073	-9999	-0.25	41	41
mol:ACh	0.002	0.026	-9999	-0.1	24	24
RAB3GAP2	0.017	0.023	-9999	-0.52	1	1
STX1A/SNAP25/VAMP2	0.018	0.053	-9999	-0.25	3	3
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	0.008	0.046	-9999	-0.34	7	7
UNC13B	0.011	0.049	-9999	-0.3	12	12
CHRNA1	0.01	0.064	-9999	-0.46	9	9
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.1	0.14	-9999	-0.22	265	265
SNAP25	-0.008	0.055	-9999	-0.29	15	15
VAMP2	0.007	0.011	-9999	-0.26	1	1
SYT1	-0.17	0.21	-9999	-0.36	265	265
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.019	0.026	-9999	-0.27	1	1
STX1A/SNAP25 fragment 1/VAMP2	0.018	0.053	-9999	-0.25	3	3

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.017	0.13	-10000	0	-0.48	37	37
HRAS	0.012	0.051	-10000	0	-0.41	7	7
EGFR	-0.079	0.18	-10000	0	-0.35	139	139
AKT	0.014	0.079	-10000	0	-0.27	24	24
FOXO3	0.011	0.053	-10000	0	-0.37	9	9
AKT1	0.011	0.053	-10000	0	-0.37	9	9
FOXO1	0	0.092	-10000	0	-0.46	19	19
AKT3	-0.006	0.084	-10000	0	-0.28	43	43
FOXO4	0.017	0.023	-10000	0	-0.52	1	1
MET	0	0.075	-10000	0	-0.29	31	31
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
PIK3CB	0.012	0.055	-10000	0	-0.44	7	7
NRAS	0.005	0.076	-10000	0	-0.4	16	16
PIK3CG	-0.007	0.1	-10000	0	-0.41	31	31
PIK3R3	0	0.091	-10000	0	-0.43	21	21
PIK3R2	0.018	0	-10000	0	-10000	0	0
NF1	0.015	0.035	-10000	0	-0.43	3	3
RAS	-0.027	0.097	0.21	1	-0.27	47	48
ERBB2	-0.027	0.12	-10000	0	-0.31	72	72
proliferation/survival/translation	-0.028	0.057	0.23	10	-0.17	3	13
PI3K	-0.019	0.099	0.18	5	-0.24	62	67
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
KRAS	0.009	0.065	-10000	0	-0.44	10	10
FOXO	0.039	0.038	-10000	0	-0.18	2	2
AKT2	0.017	0.012	-10000	0	-0.25	1	1
PTEN	-0.002	0.1	-10000	0	-0.52	19	19

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	0.019	0.27	-9999	-0.76	29	29
PCK1	0.019	0.2	-9999	-1	5	5
HNF4A	0.033	0.27	-9999	-0.84	14	14
KCNJ11	-0.015	0.38	-9999	-1	49	49
AKT1	0.011	0.17	-9999	-0.44	29	29
response to starvation	0.006	0.003	-9999	-10000	0	0
DLK1	0.019	0.3	-9999	-0.78	28	28
NKX2-1	0.074	0.14	-9999	-10000	0	0
ACADM	0.01	0.29	-9999	-0.77	35	35
TAT	0.018	0.17	-9999	-0.55	7	7
CEBPB	0.01	0.071	-9999	-0.33	20	20
CEBPA	0.011	0.085	-9999	-0.5	14	14
TTR	-0.041	0.28	-9999	-0.75	39	39
PKLR	0.022	0.26	-9999	-0.72	27	27
APOA1	0.032	0.3	-9999	-0.84	23	23
CPT1C	0	0.3	-9999	-0.85	35	35
ALAS1	0.039	0.19	-9999	-1.6	2	2
TFRC	-0.047	0.39	-9999	-1.1	47	47
FOXF1	-0.002	0.062	-9999	-0.3	19	19
NF1	0.023	0.039	-9999	-0.46	3	3
HNF1A (dimer)	0.03	0.047	-9999	-0.24	6	6
CPT1A	0.007	0.3	-9999	-0.84	33	33
HMGCS1	0.018	0.27	-9999	-0.73	28	28
NR3C1	0.007	0.1	-9999	-0.5	19	19
CPT1B	0.022	0.26	-9999	-0.74	25	25
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.02	0.04	-9999	-0.25	8	8
GCK	0.017	0.27	-9999	-0.73	31	31
CREB1	0.02	0.036	-9999	-0.51	1	1
IGFBP1	0.028	0.16	-9999	-0.73	4	4
PDX1	0.035	0.26	-9999	-1.2	13	13
UCP2	-0.025	0.35	-9999	-0.9	52	52
ALDOB	0.024	0.29	-9999	-0.79	26	26
AFP	-0.049	0.15	-9999	-0.45	20	20
BDH1	0.011	0.28	-9999	-0.75	35	35
HADH	0.021	0.3	-9999	-0.81	29	29
F2	0.032	0.3	-9999	-0.92	14	14
HNF1A	0.03	0.047	-9999	-0.24	6	6
G6PC	0.035	0.096	-9999	-1.3	1	1
SLC2A2	0.042	0.22	-9999	-1.1	5	5
INS	0.002	0.028	-9999	-0.53	1	1
FOXA1	-0.081	0.21	-9999	-0.5	104	104
FOXA3	-0.016	0.13	-9999	-0.38	31	31
FOXA2	0.032	0.35	-9999	-0.86	32	32
ABCC8	-0.2	0.52	-9999	-0.91	167	167
ALB	-0.055	0.17	-9999	-0.67	16	16

×

Regulation of Androgen receptor activity

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
HDAC1	0.025	0.017	-9999	-0.37	1	1
SMARCC1	-0.003	0.12	-9999	-1.3	4	4
REL	0	0.087	-9999	-0.41	21	21
HDAC7	-0.025	0.13	-9999	-0.39	30	30
JUN	-0.033	0.15	-9999	-0.46	57	57
EP300	0.014	0.047	-9999	-0.52	4	4
KAT2B	0	0	-9999	-10000	0	0
KAT5	0	0	-9999	-10000	0	0
MAPK14	0.002	0.084	-9999	-0.36	22	22
FOXO1	0.001	0.092	-9999	-0.46	19	19
T-DHT/AR	-0.019	0.15	-9999	-0.41	30	30
MAP2K6	-0.013	0.11	-9999	-0.4	37	37
BRM/BAF57	0.026	0.028	-9999	-0.37	2	2
MAP2K4	-0.007	0.1	-9999	-0.39	31	31
SMARCA2	0.016	0.033	-9999	-0.52	2	2
PDE9A	-0.026	0.16	-9999	-0.8	11	11
NCOA2	0.01	0.063	-9999	-0.4	11	11
CEBPA	0.004	0.084	-9999	-0.5	14	14
EHMT2	0.018	0.001	-9999	-10000	0	0
cell proliferation	0.007	0.13	-9999	-0.36	23	23
NR0B1	-0.01	0.087	-9999	-0.27	51	51
EGR1	-0.1	0.2	-9999	-0.39	156	156
RXRs/9cRA	0.025	0.057	-9999	-0.28	18	18
AR/RACK1/Src	0.003	0.1	-9999	-0.34	20	20
AR/GR	-0.038	0.13	-9999	-0.29	73	73
GNB2L1	0.015	0.04	-9999	-0.52	3	3
PKN1	0.013	0.045	-9999	-0.39	6	6
RCHY1	0.002	0.09	-9999	-0.5	16	16
epidermal growth factor receptor activity	0	0.001	-9999	-0.005	6	6
MAPK8	0.004	0.08	-9999	-0.38	18	18
T-DHT/AR/TIF2/CARM1	0	0.11	-9999	-0.36	22	22
SRC	0.005	0.09	-9999	-0.28	38	38
NR3C1	-0.001	0.098	-9999	-0.51	19	19
KLK3	-0.038	0.11	-9999	-0.46	6	6
APPBP2	0.009	0.042	-9999	-0.25	13	13
TRIM24	0.017	0.024	-9999	-0.25	4	4
T-DHT/AR/TIP60	-0.021	0.1	-9999	-0.31	42	42
TMPRSS2	-0.18	0.43	-9999	-1.1	95	95
RXRG	0.004	0.083	-9999	-0.47	15	15
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.015	0.04	-9999	-0.52	3	3
RXRB	0.015	0.04	-9999	-0.52	3	3
CARM1	0.015	0.039	-9999	-0.36	5	5
NR2C2	0.016	0.02	-9999	-0.25	3	3
KLK2	0.021	0.095	-9999	-0.4	4	4
AR	-0.04	0.13	-9999	-0.28	106	106
SENP1	0.018	0	-9999	-10000	0	0
HSP90AA1	0.013	0.045	-9999	-0.39	6	6
MDM2	0.009	0.044	-9999	-0.26	14	14
SRY	0.001	0.085	-9999	-0.43	18	18
GATA2	-0.007	0.093	-9999	-0.31	40	40
MYST2	0.011	0.047	-9999	-0.31	10	10
HOXB13	-0.074	0.13	-9999	-0.25	182	182
T-DHT/AR/RACK1/Src	-0.002	0.11	-9999	-0.35	20	20
positive regulation of transcription	-0.007	0.093	-9999	-0.31	40	40
DNAJA1	0.012	0.043	-9999	-0.46	4	4
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.06	-9999	-0.31	16	16
NCOA1	0.016	0.063	-9999	-0.55	6	6
SPDEF	-0.081	0.21	-9999	-0.52	98	98
T-DHT/AR/TIF2	0.009	0.08	-9999	-0.3	11	11
T-DHT/AR/Hsp90	-0.012	0.11	-9999	-0.36	22	22
GSK3B	0.018	0.003	-9999	-10000	0	0
NR2C1	0.01	0.062	-9999	-0.52	7	7
mol:T-DHT	-0.002	0.095	-9999	-0.3	36	36
SIRT1	0.016	0.029	-9999	-0.34	3	3
ZMIZ2	0.016	0.002	-9999	-10000	0	0
POU2F1	0.014	0.038	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.022	0.12	-9999	-0.31	45	45
CREBBP	0.016	0.033	-9999	-0.52	2	2
SMARCE1	0.017	0.021	-9999	-0.26	3	3

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.017	0.023	-9999	-0.52	1	1
SPHK1	-0.027	0.14	-9999	-0.42	54	54
GNAI2	0.006	0.075	-9999	-0.48	12	12
mol:S1P	-0.001	0.087	-9999	-0.3	35	35
GNAO1	0.016	0.024	-9999	-0.25	4	4
mol:Sphinganine-1-P	-0.007	0.1	-9999	-0.38	33	33
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.015	0.075	-9999	-0.39	8	8
GNAI3	0.018	0	-9999	-10000	0	0
G12/G13	0.021	0.039	-9999	-0.37	4	4
S1PR3	0	0	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	-0.019	0.12	-9999	-0.4	46	46
S1P1/S1P	-0.012	0.11	-9999	-0.28	58	58
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
GNAI1	-0.017	0.12	-9999	-0.38	46	46
S1P/S1P5/G12	0.008	0.07	-9999	-0.23	35	35
S1P/S1P3/Gq	-0.026	0.11	-9999	-0.28	66	66
S1P/S1P4/Gi	0.006	0.087	-9999	-0.32	20	20
GNAQ	0	0	-9999	-10000	0	0
GNAZ	0.001	0.088	-9999	-0.44	19	19
GNA14	-0.079	0.18	-9999	-0.35	140	140
GNA15	0.002	0.076	-9999	-0.34	23	23
GNA12	0.018	0	-9999	-10000	0	0
GNA13	0.011	0.055	-9999	-0.36	10	10
GNA11	0.014	0.047	-9999	-0.52	4	4
ABCC1	0.012	0.051	-9999	-0.41	7	7

×

S1P1 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0	0.1	-9999	-0.36	30	30
PDGFRB	0.01	0.067	-9999	-0.53	8	8
SPHK1	-0.054	0.19	-9999	-0.76	33	33
mol:S1P	-0.049	0.17	-9999	-0.65	35	35
S1P1/S1P/Gi	-0.002	0.15	-9999	-0.49	25	25
GNAO1	0.016	0.024	-9999	-0.26	4	4
PDGFB-D/PDGFRB/PLCgamma1	0.008	0.14	-9999	-0.49	21	21
PLCG1	0.004	0.14	-9999	-0.48	22	22
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.01	0.067	-9999	-0.53	8	8
GNAI2	0.007	0.076	-9999	-0.48	12	12
GNAI3	0.018	0.003	-9999	-10000	0	0
GNAI1	-0.016	0.12	-9999	-0.38	46	46
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.012	0.16	-9999	-0.52	38	38
S1P1/S1P	-0.026	0.19	-9999	-0.51	56	56
negative regulation of cAMP metabolic process	-0.001	0.14	-9999	-0.47	25	25
MAPK3	0.002	0.16	-9999	-0.53	22	22
calcium-dependent phospholipase C activity	0	0.003	-9999	-10000	0	0
Rac1/GDP	0.013	0	-9999	-10000	0	0
RhoA/GDP	0.004	0.058	-9999	-0.38	12	12
KDR	0.006	0.076	-9999	-0.65	5	5
PLCB2	-0.015	0.17	-9999	-0.44	56	56
RAC1	0.018	0	-9999	-10000	0	0
RhoA/GTP	-0.061	0.14	-9999	-0.42	59	59
receptor internalization	-0.024	0.17	-9999	-0.47	57	57
PTGS2	-0.001	0.17	-9999	-0.72	14	14
Rac1/GTP	-0.056	0.14	-9999	-0.42	56	56
RHOA	0.005	0.08	-9999	-0.52	12	12
VEGFA	-0.006	0.085	-9999	-0.29	31	31
negative regulation of T cell proliferation	-0.001	0.14	-9999	-0.47	25	25
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.002	0.088	-9999	-0.44	19	19
MAPK1	0.002	0.16	-9999	-0.53	22	22
S1P1/S1P/PDGFB-D/PDGFRB	-0.016	0.2	-9999	-0.49	57	57
ABCC1	0.012	0.051	-9999	-0.41	7	7

×

PLK1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.001	0.05	0.26	17	-10000	0	17
BUB1B	-0.017	0.12	-10000	0	-0.42	39	39
PLK1	0.002	0.041	-10000	0	-0.12	44	44
PLK1S1	0.002	0.019	-10000	0	-0.054	41	41
KIF2A	0.005	0.054	-10000	0	-0.28	10	10
regulation of mitotic centrosome separation	0.002	0.041	-10000	0	-0.12	44	44
GOLGA2	0.016	0.026	-10000	0	-0.39	2	2
Hec1/SPC24	-0.012	0.094	-10000	0	-0.31	39	39
WEE1	-0.003	0.093	-10000	0	-0.35	25	25
cytokinesis	-0.025	0.16	-10000	0	-0.52	44	44
PP2A-alpha B56	-0.059	0.27	-10000	0	-0.76	62	62
AURKA	-0.002	0.064	-10000	0	-0.28	23	23
PICH/PLK1	-0.023	0.18	-10000	0	-0.55	42	42
CENPE	-0.011	0.096	-10000	0	-0.33	37	37
RhoA/GTP	0.004	0.058	-10000	0	-0.38	12	12
positive regulation of microtubule depolymerization	0.005	0.054	-10000	0	-0.28	10	10
PPP2CA	0.011	0.062	-10000	0	-0.52	7	7
FZR1	0.018	0	-10000	0	-10000	0	0
TPX2	-0.013	0.083	-10000	0	-0.29	40	40
PAK1	-0.023	0.13	-10000	0	-0.38	54	54
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	0.015	0.035	-10000	0	-0.43	3	3
CLSPN	0.002	0.057	-10000	0	-0.33	12	12
GORASP1	0.017	0.023	-10000	0	-0.52	1	1
metaphase	0	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.002	0.019	-10000	0	-0.054	41	41
G2 phase of mitotic cell cycle	-0.001	0.003	0.016	1	-0.013	21	22
STAG2	0.017	0.023	-10000	0	-0.52	1	1
GRASP65/GM130/RAB1/GTP	0.021	0.04	-10000	0	-0.74	1	1
spindle elongation	0.002	0.041	-10000	0	-0.12	44	44
ODF2	0.016	0.024	-10000	0	-0.53	1	1
BUB1	-0.1	0.28	-10000	0	-0.85	60	60
TPT1	0.009	0.019	-10000	0	-10000	0	0
CDC25C	-0.016	0.11	-10000	0	-0.44	34	34
CDC25B	0.004	0.069	-10000	0	-0.3	23	23
SGOL1	-0.001	0.051	-10000	0	-0.26	17	17
RHOA	0.005	0.08	-10000	0	-0.52	12	12
CCNB1/CDK1	-0.013	0.15	-10000	0	-0.5	40	40
CDC14B	0.01	0.03	-10000	0	-0.38	3	3
CDC20	-0.02	0.12	-10000	0	-0.37	51	51
PLK1/PBIP1	-0.011	0.083	-10000	0	-0.29	37	37
mitosis	0.002	0.007	0.034	22	-10000	0	22
FBXO5	0.003	0.054	-10000	0	-0.19	20	20
CDC2	-0.012	0.12	-10000	0	-0.45	34	34
NDC80	-0.029	0.14	-10000	0	-0.41	57	57
metaphase plate congression	0.009	0.023	-10000	0	-10000	0	0
ERCC6L	-0.026	0.19	-10000	0	-0.6	42	42
NLP/gamma Tubulin	0.005	0.022	-10000	0	-0.075	5	5
microtubule cytoskeleton organization	0.009	0.019	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.002	0.011	5	-10000	0	5
PPP1R12A	0.015	0.031	-10000	0	-0.32	4	4
interphase	0	0.002	0.011	5	-10000	0	5
PLK1/PRC1-2	-0.017	0.14	-10000	0	-0.42	49	49
GRASP65/GM130/RAB1/GTP/PLK1	0.028	0.039	-10000	0	-0.22	3	3
RAB1A	0.017	0.023	-10000	0	-0.52	1	1
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.006	0.039	-10000	0	-0.15	18	18
mitotic prometaphase	0	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.058	-10000	0	-0.33	5	5
microtubule-based process	-0.011	0.1	-10000	0	-0.34	40	40
Golgi organization	0.002	0.041	-10000	0	-0.12	44	44
Cohesin/SA2	0.009	0.036	-10000	0	-0.16	5	5
PPP1CB/MYPT1	0.023	0.026	-10000	0	-0.37	1	1
KIF20A	-0.027	0.14	-10000	0	-0.46	49	49
APC/C/CDC20	-0.007	0.089	-10000	0	-0.34	28	28
PPP2R1A	0.017	0.012	-10000	0	-0.25	1	1
chromosome segregation	-0.011	0.082	-10000	0	-0.28	37	37
PRC1	-0.019	0.13	-10000	0	-0.43	43	43
ECT2	-0.001	0.07	-10000	0	-0.31	18	18
C13orf34	0.006	0.037	-10000	0	-0.13	14	14
NUDC	0.009	0.023	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.016	0.12	-10000	0	-0.41	39	39
spindle assembly	0.005	0.031	-10000	0	-0.093	27	27
spindle stabilization	0.002	0.019	-10000	0	-0.053	41	41
APC/C/HCDH1	0.02	0.025	-10000	0	-0.32	3	3
MKLP2/PLK1	-0.011	0.1	-10000	0	-0.34	40	40
CCNB1	-0.016	0.13	-10000	0	-0.5	35	35
PPP1CB	0.016	0.02	-10000	0	-0.25	3	3
BTRC	0.008	0.054	-10000	0	-0.29	16	16
ROCK2	0.008	0.055	-10000	0	-0.34	7	7
TUBG1	0.008	0.02	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.046	0.14	-10000	0	-0.48	40	40
MLF1IP	-0.018	0.1	-10000	0	-0.32	49	49
INCENP	0.001	0.081	-10000	0	-0.37	22	22

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.019	0.052	-9999	-0.37	9	9
FBXW11	0.015	0.035	-9999	-0.43	3	3
NF kappa B1 p50/c-Rel	0.018	0.062	-9999	-0.31	15	15
NF kappa B1 p50/RelA/I kappa B alpha	0	0.11	-9999	-0.44	18	18
NFKBIA	-0.024	0.12	-9999	-0.26	87	87
MAPK14	0.017	0.012	-9999	-0.25	1	1
NF kappa B1 p105/p50	0.026	0.038	-9999	-0.3	5	5
ARRB2	0.02	0.005	-9999	-10000	0	0
REL	0.001	0.087	-9999	-0.41	21	21
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.022	0.054	-9999	-0.3	12	12
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.028	0.031	-9999	-0.3	3	3
PIK3CA	0.016	0.029	-9999	-0.34	3	3
NF kappa B1 p50 dimer	0.019	0.037	-9999	-0.37	3	3
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
NFKB1	0.02	0.037	-9999	-0.37	3	3
RELA	0.018	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	-0.014	0.1	-9999	-0.23	85	85
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.005	0.11	-9999	-0.44	17	17
SRC	0.015	0.035	-9999	-0.43	3	3
PI3K	0.005	0.082	-9999	-0.37	21	21
NF kappa B1 p50/RelA	-0.014	0.1	-9999	-0.23	85	85
IKBKB	0.012	0.047	-9999	-0.31	10	10
beta TrCP1/SCF ubiquitin ligase complex	0.015	0.035	-9999	-0.43	3	3
SYK	-0.023	0.14	-9999	-0.48	43	43
I kappa B alpha/PIK3R1	-0.027	0.13	-9999	-0.37	39	39
cell death	0.005	0.1	-9999	-0.42	17	17
NF kappa B1 p105/c-Rel	0.018	0.062	-9999	-0.31	15	15
LCK	-0.074	0.18	-9999	-0.4	117	117
BCL3	0.008	0.071	-9999	-0.5	10	10

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	0.041	0.17	-10000	0	-0.9	12	12
NCK1/PAK1/Dok-R	-0.032	0.083	-10000	0	-0.46	11	11
NCK1/Dok-R	0.029	0.18	-10000	0	-1.1	11	11
PIK3CA	0.015	0.029	-10000	0	-0.34	3	3
mol:beta2-estradiol	-0.009	0.02	0.24	1	-10000	0	1
RELA	0.018	0	-10000	0	-10000	0	0
SHC1	0.017	0.024	-10000	0	-0.52	1	1
Rac/GDP	0.013	0	-10000	0	-10000	0	0
F2	0.006	0.021	0.26	1	-10000	0	1
TNIP2	0.012	0.052	-10000	0	-0.39	8	8
NF kappa B/RelA	0.052	0.15	-10000	0	-0.9	11	11
FN1	-0.048	0.17	-10000	0	-0.46	73	73
PLD2	0.037	0.16	-10000	0	-1	11	11
PTPN11	0.017	0.023	-10000	0	-0.52	1	1
GRB14	-0.16	0.21	-10000	0	-0.36	247	247
ELK1	0.046	0.15	-10000	0	-0.92	11	11
GRB7	-0.017	0.1	-10000	0	-0.29	59	59
PAK1	-0.022	0.13	-10000	0	-0.37	54	54
Tie2/Ang1/alpha5/beta1 Integrin	0.022	0.19	-10000	0	-1	11	11
CDKN1A	0.02	0.2	-10000	0	-0.76	28	28
ITGA5	0.015	0.035	-10000	0	-0.43	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.026	0.18	-10000	0	-1	12	12
CRK	0.016	0.033	-10000	0	-0.52	2	2
mol:NO	0.05	0.14	-10000	0	-0.66	12	12
PLG	0.039	0.16	-10000	0	-1	11	11
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.048	0.16	-10000	0	-0.87	11	11
GRB2	0.016	0.024	-10000	0	-0.25	4	4
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
ANGPT2	-0.018	0.16	-10000	0	-0.75	10	10
BMX	0.012	0.19	-10000	0	-1.2	11	11
ANGPT1	0.021	0.085	-10000	0	-1.2	1	1
tube development	0.026	0.17	-10000	0	-0.74	16	16
ANGPT4	0.017	0.026	-10000	0	-0.39	2	2
response to hypoxia	0.003	0.011	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.045	0.19	-10000	0	-1.1	11	11
alpha5/beta1 Integrin	0.022	0.041	-10000	0	-0.37	5	5
FGF2	-0.065	0.16	-10000	0	-0.34	122	122
STAT5A (dimer)	0.026	0.21	-10000	0	-0.79	25	25
mol:L-citrulline	0.05	0.14	-10000	0	-0.66	12	12
AGTR1	-0.15	0.21	-10000	0	-0.36	231	231
MAPK14	0.035	0.18	-10000	0	-1.1	11	11
Tie2/SHP2	0.027	0.16	-10000	0	-1.1	10	10
TEK	0.024	0.18	-10000	0	-1.2	10	10
RPS6KB1	0.04	0.16	-10000	0	-0.88	11	11
Angiotensin II/AT1	-0.099	0.15	-10000	0	-0.25	231	231
Tie2/Ang1/GRB2	0.04	0.16	-10000	0	-1	11	11
MAPK3	0.043	0.15	-10000	0	-0.92	11	11
MAPK1	0.042	0.15	-10000	0	-0.92	11	11
Tie2/Ang1/GRB7	0.025	0.17	-10000	0	-1	11	11
NFKB1	0.017	0.023	-10000	0	-0.52	1	1
MAPK8	0.038	0.16	-10000	0	-1	11	11
PI3K	0.035	0.19	-10000	0	-1.1	11	11
FES	0.031	0.19	-10000	0	-1.1	12	12
Crk/Dok-R	0.031	0.18	-10000	0	-1	11	11
Tie2/Ang1/ABIN2	0.038	0.16	-10000	0	-1	11	11
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.043	0.16	-10000	0	-0.8	12	12
STAT5A	0.011	0.056	-10000	0	-0.42	8	8
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.043	0.16	-10000	0	-0.88	11	11
Tie2/Ang2	0.015	0.22	-10000	0	-1	15	15
Tie2/Ang1	0.034	0.17	-10000	0	-1.1	11	11
FOXO1	0.043	0.17	-10000	0	-0.77	16	16
ELF1	0.017	0.073	-10000	0	-0.49	10	10
ELF2	0.037	0.16	-10000	0	-1	11	11
mol:Choline	0.038	0.16	-10000	0	-0.96	11	11
cell migration	-0.023	0.051	-10000	0	-0.22	20	20
FYN	0.023	0.19	-10000	0	-0.85	16	16
DOK2	-0.021	0.13	-10000	0	-0.4	48	48
negative regulation of cell cycle	0.024	0.18	-10000	0	-0.67	28	28
ETS1	0.011	0.075	-10000	0	-0.3	24	24
PXN	0.05	0.14	-10000	0	-0.72	11	11
ITGB1	0.014	0.044	-10000	0	-0.41	5	5
NOS3	0.049	0.15	-10000	0	-0.75	12	12
RAC1	0.018	0	-10000	0	-10000	0	0
TNF	0.004	0.097	-10000	0	-0.35	32	32
MAPKKK cascade	0.038	0.16	-10000	0	-0.96	11	11
RASA1	0.004	0.078	-10000	0	-0.42	16	16
Tie2/Ang1/Shc	0.041	0.16	-10000	0	-1	11	11
NCK1	0.011	0.045	-10000	0	-0.28	12	12
vasculogenesis	0.051	0.13	-10000	0	-0.59	12	12
mol:Phosphatidic acid	0.038	0.16	-10000	0	-0.96	11	11
mol:Angiotensin II	0.002	0.002	-10000	0	-10000	0	0
mol:NADP	0.05	0.14	-10000	0	-0.66	12	12
Rac1/GTP	-0.011	0.14	-10000	0	-0.82	11	11
MMP2	0.016	0.19	-10000	0	-1.1	11	11

×

Arf6 downstream pathway

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
PLAUR	-0.022	0.26	-10000	0	-1.1	30	30
regulation of axonogenesis	-0.012	0.065	0.35	8	-10000	0	8
myoblast fusion	0.003	0.1	0.4	31	-10000	0	31
mol:GTP	-0.002	0.062	-10000	0	-0.24	32	32
regulation of calcium-dependent cell-cell adhesion	-0.018	0.082	0.25	39	-10000	0	39
ARF1/GTP	0.012	0.05	-10000	0	-0.32	3	3
mol:GM1	0	0.047	-10000	0	-0.25	4	4
mol:Choline	0.007	0.075	-10000	0	-0.34	16	16
lamellipodium assembly	-0.001	0.11	-10000	0	-0.43	32	32
MAPK3	0.009	0.089	-10000	0	-0.33	33	33
ARF6/GTP/NME1/Tiam1	0.019	0.083	-10000	0	-0.25	39	39
ARF1	0.017	0.023	-10000	0	-0.52	1	1
ARF6/GDP	-0.003	0.1	-10000	0	-0.4	31	31
ARF1/GDP	0.006	0.097	-10000	0	-0.36	33	33
ARF6	0.007	0.05	-10000	0	-0.62	2	2
RAB11A	0.016	0.029	-10000	0	-0.34	3	3
TIAM1	0.007	0.074	-10000	0	-0.44	13	13
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.009	0.09	-10000	0	-0.33	34	34
actin filament bundle formation	0.001	0.11	0.35	41	-10000	0	41
KALRN	-0.022	0.078	-10000	0	-0.31	32	32
RAB11FIP3/RAB11A	0.019	0.05	-10000	0	-0.37	8	8
RhoA/GDP	-0.001	0.11	-10000	0	-0.36	41	41
NME1	0.012	0.039	-10000	0	-0.25	11	11
Rac1/GDP	0.005	0.096	-10000	0	-0.36	32	32
substrate adhesion-dependent cell spreading	-0.002	0.062	-10000	0	-0.24	32	32
cortical actin cytoskeleton organization	-0.002	0.11	-10000	0	-0.43	32	32
RAC1	0.018	0	-10000	0	-10000	0	0
liver development	-0.002	0.062	-10000	0	-0.24	32	32
ARF6/GTP	-0.002	0.062	-10000	0	-0.24	32	32
RhoA/GTP	0.004	0.074	-10000	0	-0.36	14	14
mol:GDP	-0.003	0.1	-10000	0	-0.4	32	32
ARF6/GTP/RAB11FIP3/RAB11A	0.019	0.058	-10000	0	-0.28	10	10
RHOA	0.005	0.08	-10000	0	-0.52	12	12
PLD1	0.001	0.078	-10000	0	-0.37	13	13
RAB11FIP3	0.01	0.063	-10000	0	-0.49	8	8
tube morphogenesis	-0.001	0.11	-10000	0	-0.43	32	32
ruffle organization	0.012	0.065	-10000	0	-0.35	8	8
regulation of epithelial cell migration	-0.002	0.062	-10000	0	-0.24	32	32
PLD2	0.01	0.06	-10000	0	-0.38	6	6
PIP5K1A	0.012	0.065	-10000	0	-0.35	8	8
mol:Phosphatidic acid	0.007	0.075	-10000	0	-0.34	16	16
Rac1/GTP	-0.002	0.11	-10000	0	-0.44	32	32

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0.015	0.035	-10000	0	-0.43	3	3
MKNK1	0.018	0	-10000	0	-10000	0	0
mol:PIP3	-0.037	0.11	0.25	10	-0.28	70	80
FRAP1	0.015	0.034	-10000	0	-10000	0	0
AKT1	-0.011	0.1	0.22	8	-0.25	71	79
INSR	0.015	0.037	-10000	0	-0.39	4	4
Insulin Receptor/Insulin	0.021	0.027	-10000	0	-0.31	3	3
mol:GTP	0.004	0.085	-10000	0	-0.24	28	28
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.01	0.027	-10000	0	-0.18	1	1
TSC2	0.016	0.026	-10000	0	-0.39	2	2
RHEB/GDP	-0.026	0.062	-10000	0	-0.27	15	15
TSC1	0.018	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.022	0.12	-10000	0	-0.33	62	62
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.011	0.031	-10000	0	-0.19	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.017	0.012	-10000	0	-0.25	1	1
RPS6KB1	0.01	0.065	0.19	8	-0.26	5	13
MAP3K5	-0.014	0.089	-10000	0	-0.36	30	30
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
apoptosis	-0.014	0.089	-10000	0	-0.36	30	30
mol:LY294002	0	0.001	0.001	1	-0.001	67	68
EIF4B	0.016	0.062	0.18	8	-0.24	7	15
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.02	0.057	-10000	0	-0.24	3	3
eIF4E/eIF4G1/eIF4A1	-0.002	0.014	-10000	0	-10000	0	0
KIAA1303	0.015	0.031	-10000	0	-0.32	4	4
PI3K	-0.02	0.12	-10000	0	-0.3	79	79
mTOR/RHEB/GTP/Raptor/GBL	0.032	0.054	0.18	8	-0.3	2	10
FKBP1A	0.017	0.017	-10000	0	-0.25	2	2
RHEB/GTP	0.009	0.076	-10000	0	-0.27	15	15
mol:Amino Acids	0	0.001	0.001	1	-0.001	67	68
FKBP12/Rapamycin	0.012	0.011	-10000	0	-0.17	2	2
PDPK1	-0.014	0.1	0.23	8	-0.26	70	78
EIF4E	0.018	0	-10000	0	-10000	0	0
ASK1/PP5C	-0.011	0.15	-10000	0	-0.59	30	30
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.035	0.056	-10000	0	-0.56	4	4
TSC1/TSC2	0.009	0.095	0.22	8	-0.32	14	22
tumor necrosis factor receptor activity	0	0.001	0.001	67	-0.001	1	68
RPS6	0.015	0.037	-10000	0	-0.39	4	4
PPP5C	0.012	0.052	-10000	0	-0.39	8	8
EIF4G1	0.014	0.047	-10000	0	-0.52	4	4
IRS1	-0.034	0.12	-10000	0	-0.36	61	61
INS	0.017	0.023	-10000	0	-0.52	1	1
PTEN	-0.002	0.1	-10000	0	-0.52	19	19
PDK2	-0.02	0.11	0.23	8	-0.27	76	84
EIF4EBP1	-0.012	0.16	-10000	0	-1.1	10	10
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
PPP2R5D	0.021	0.033	-10000	0	-10000	0	0
peptide biosynthetic process	0.025	0.03	-10000	0	-0.28	5	5
RHEB	0.016	0.026	-10000	0	-0.39	2	2
EIF4A1	0.018	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.003	15	-0.002	6	21
EEF2	0.025	0.031	-10000	0	-0.28	5	5
eIF4E/4E-BP1	-0.001	0.14	-10000	0	-1	10	10

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.008	0.081	-9999	-0.29	23	23
BIRC5	-0.037	0.15	-9999	-0.41	67	67
NFKBIA	0.024	0.054	-9999	-0.33	3	3
CPEB1	0.003	0.071	-9999	-0.31	23	23
AKT1	0.022	0.057	-9999	-0.28	5	5
NDEL1	0.018	0	-9999	-10000	0	0
Aurora A/BRCA1	0.013	0.067	-9999	-0.28	16	16
NDEL1/TACC3	0.021	0.079	-9999	-0.36	16	16
GADD45A	-0.011	0.11	-9999	-0.39	38	38
GSK3B	0.021	0.015	-9999	-10000	0	0
PAK1/Aurora A	0.002	0.087	-9999	-0.3	25	25
MDM2	0.011	0.044	-9999	-0.25	14	14
JUB	-0.027	0.15	-9999	-0.49	47	47
TPX2	-0.009	0.11	-9999	-0.37	40	40
TP53	0.004	0.089	-9999	-0.29	37	37
DLG7	-0.005	0.11	-9999	-0.35	44	44
AURKAIP1	0.016	0.029	-9999	-0.34	3	3
ARHGEF7	0.016	0.02	-9999	-0.25	3	3
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.022	0.083	-9999	-0.38	16	16
G2/M transition of mitotic cell cycle	0.013	0.066	-9999	-0.28	16	16
AURKA	0.021	0.058	-9999	-0.21	21	21
AURKB	-0.007	0.078	-9999	-0.32	21	21
CDC25B	0.011	0.069	-9999	-0.31	8	8
G2/M transition checkpoint	-0.002	0.088	-9999	-0.27	42	42
mRNA polyadenylation	0.015	0.054	-9999	-0.26	6	6
Aurora A/CPEB	0.016	0.055	-9999	-0.26	6	6
Aurora A/TACC1/TRAP/chTOG	0.016	0.093	-9999	-0.26	37	37
BRCA1	0	0.094	-9999	-0.48	19	19
centrosome duplication	0.002	0.087	-9999	-0.3	25	25
regulation of centrosome cycle	0.02	0.078	-9999	-0.35	16	16
spindle assembly	0.015	0.092	-9999	-0.26	37	37
TDRD7	0.004	0.084	-9999	-0.5	14	14
Aurora A/RasGAP/Survivin	-0.001	0.12	-9999	-0.3	57	57
CENPA	-0.016	0.12	-9999	-0.36	46	46
Aurora A/PP2A	0.025	0.047	-9999	-0.21	1	1
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.008	0.088	-9999	-0.33	21	21
negative regulation of DNA binding	0.004	0.089	-9999	-0.29	37	37
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.023	0.028	-9999	-0.37	1	1
RASA1	0.004	0.078	-9999	-0.42	16	16
Ajuba/Aurora A	-0.002	0.089	-9999	-0.27	42	42
mitotic prometaphase	-0.001	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.058	-9999	-0.21	21	21
TACC1	-0.022	0.13	-9999	-0.41	49	49
TACC3	-0.006	0.11	-9999	-0.47	26	26
Aurora A/Antizyme1	0.034	0.044	-9999	-0.27	1	1
Aurora A/RasGAP	0.018	0.066	-9999	-0.3	11	11
OAZ1	0.018	0	-9999	-10000	0	0
RAN	0.017	0.012	-9999	-0.25	1	1
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.021	0.015	-9999	-10000	0	0
GIT1	0.014	0.035	-9999	-0.3	6	6
GIT1/beta-PIX/PAK1	0.009	0.084	-9999	-0.32	24	24
Importin alpha/Importin beta/TPX2	-0.009	0.11	-9999	-0.37	40	40
PPP2R5D	0.016	0.02	-9999	-0.25	3	3
Aurora A/TPX2	0.006	0.1	-9999	-0.4	26	26
PAK1	-0.022	0.13	-9999	-0.37	54	54
CKAP5	0.017	0.017	-9999	-0.25	2	2

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.054	0.27	-10000	0	-1.2	28	28
oxygen homeostasis	0.007	0.013	-10000	0	-10000	0	0
TCEB2	0.018	0	-10000	0	-10000	0	0
TCEB1	0.014	0.035	-10000	0	-0.3	6	6
VHL/Elongin B/Elongin C/HIF2A	0.035	0.13	-10000	0	-0.38	21	21
EPO	0.051	0.23	-10000	0	-0.58	28	28
FIH (dimer)	0.024	0.027	-10000	0	-0.52	1	1
APEX1	0.024	0.019	-10000	0	-0.26	1	1
SERPINE1	0.051	0.26	-10000	0	-0.7	31	31
FLT1	-0.023	0.2	-10000	0	-1.1	15	15
ADORA2A	0.041	0.25	-10000	0	-0.66	33	33
germ cell development	0.066	0.23	-10000	0	-0.62	26	26
SLC11A2	0.064	0.24	-10000	0	-0.66	27	27
BHLHE40	0.056	0.23	-10000	0	-0.62	31	31
HIF1AN	0.024	0.027	-10000	0	-0.53	1	1
HIF2A/ARNT/SIRT1	0.039	0.17	-10000	0	-0.43	30	30
ETS1	0.018	0.075	-10000	0	-0.3	24	24
CITED2	-0.013	0.15	-10000	0	-1.1	9	9
KDR	-0.01	0.15	-10000	0	-1.1	9	9
PGK1	0.066	0.23	-10000	0	-0.65	25	25
SIRT1	0.015	0.029	-10000	0	-0.35	3	3
response to hypoxia	-0.001	0.003	-10000	0	-10000	0	0
HIF2A/ARNT	0.082	0.27	-10000	0	-0.72	31	31
EPAS1	0.018	0.15	-10000	0	-0.38	35	35
SP1	0.023	0.027	-10000	0	-0.52	1	1
ABCG2	0.058	0.25	-10000	0	-0.69	30	30
EFNA1	0.056	0.25	-10000	0	-0.63	34	34
FXN	0.057	0.23	-10000	0	-0.65	25	25
POU5F1	0.066	0.23	-10000	0	-0.65	26	26
neuron apoptosis	-0.081	0.27	0.7	31	-10000	0	31
EP300	0.014	0.047	-10000	0	-0.52	4	4
EGLN3	-0.066	0.18	-10000	0	-0.39	116	116
EGLN2	0.018	0.054	-10000	0	-0.36	9	9
EGLN1	0.008	0.084	-10000	0	-0.35	24	24
VHL/Elongin B/Elongin C	0.032	0.027	-10000	0	-0.3	1	1
VHL	0.015	0.029	-10000	0	-0.25	6	6
ARNT	0.025	0.014	-10000	0	-10000	0	0
SLC2A1	0.051	0.24	-10000	0	-0.65	29	29
TWIST1	0.035	0.27	-10000	0	-0.7	43	43
ELK1	0.022	0.038	-10000	0	-0.38	4	4
HIF2A/ARNT/Cbp/p300	0.052	0.17	-10000	0	-0.44	27	27
VEGFA	0.058	0.24	-10000	0	-0.65	28	28
CREBBP	0.016	0.033	-10000	0	-0.52	2	2

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.012	0.14	-9999	-0.44	32	32
PDGFB-D/PDGFRB/SLAP	0.01	0.074	-9999	-0.38	17	17
PDGFB-D/PDGFRB/APS/CBL	0.018	0.042	-9999	-0.32	8	8
AKT1	-0.021	0.14	-9999	-0.39	34	34
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.006	0.13	-9999	-0.49	22	22
PIK3CA	0.016	0.029	-9999	-0.34	3	3
FGR	-0.008	0.065	-9999	-0.39	10	10
mol:Ca2+	0.004	0.11	-9999	-0.62	11	11
MYC	-0.029	0.22	-9999	-0.74	42	42
SHC1	0.017	0.023	-9999	-0.52	1	1
HRAS/GDP	0.02	0.069	-9999	-0.25	25	25
LRP1/PDGFRB/PDGFB	0.024	0.064	-9999	-0.35	13	13
GRB10	-0.003	0.097	-9999	-0.43	24	24
PTPN11	0.017	0.023	-9999	-0.52	1	1
GO:0007205	0.003	0.11	-9999	-0.63	11	11
PTEN	-0.002	0.1	-9999	-0.52	19	19
GRB2	0.016	0.024	-9999	-0.25	4	4
GRB7	-0.017	0.1	-9999	-0.29	59	59
PDGFB-D/PDGFRB/SHP2	0.019	0.052	-9999	-0.37	9	9
PDGFB-D/PDGFRB/GRB10	0.005	0.086	-9999	-0.37	24	24
cell cycle arrest	0.01	0.074	-9999	-0.37	17	17
HRAS	0.012	0.051	-9999	-0.41	7	7
HIF1A	-0.035	0.14	-9999	-0.34	49	49
GAB1	-0.011	0.13	-9999	-0.61	15	15
mol:GTP	0	0	-9999	-10000	0	0
DNM2	-0.008	0.13	-9999	-0.59	14	14
PDGFB-D/PDGFRB	0.019	0.067	-9999	-0.35	12	12
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.016	0.062	-9999	-0.37	13	13
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.017	0.15	-9999	-0.47	33	33
positive regulation of MAPKKK cascade	0.019	0.052	-9999	-0.37	9	9
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
mol:IP3	0.003	0.11	-9999	-0.64	11	11
E5	0	0.002	-9999	-10000	0	0
CSK	0.015	0.031	-9999	-0.32	4	4
PDGFB-D/PDGFRB/GRB7	-0.004	0.085	-9999	-0.37	16	16
SHB	0.008	0.067	-9999	-0.41	12	12
BLK	-0.024	0.091	-9999	-0.45	18	18
PTPN2	0.015	0.024	-9999	-0.26	4	4
PDGFB-D/PDGFRB/SNX15	0.019	0.05	-9999	-0.37	8	8
BCAR1	0.017	0.012	-9999	-0.25	1	1
VAV2	-0.011	0.14	-9999	-0.53	21	21
CBL	0.017	0.012	-9999	-0.25	1	1
PDGFB-D/PDGFRB/DEP1	0.015	0.063	-9999	-0.37	13	13
LCK	-0.082	0.2	-9999	-0.57	68	68
PDGFRB	0.009	0.067	-9999	-0.53	8	8
ACP1	0.013	0.052	-9999	-0.52	5	5
HCK	-0.029	0.14	-9999	-0.55	28	28
ABL1	-0.005	0.11	-9999	-0.49	17	17
PDGFB-D/PDGFRB/CBL	-0.01	0.14	-9999	-0.64	16	16
PTPN1	0.001	0.07	-9999	-0.28	28	28
SNX15	0.017	0.012	-9999	-0.25	1	1
STAT3	0.015	0.04	-9999	-0.52	3	3
STAT1	-0.02	0.12	-9999	-0.33	58	58
cell proliferation	-0.022	0.2	-9999	-0.64	43	43
SLA	0.004	0.078	-9999	-0.39	18	18
actin cytoskeleton reorganization	0.032	0.07	-9999	-0.37	7	7
SRC	-0.009	0.083	-9999	-0.46	12	12
PI3K	-0.066	0.12	-9999	-0.44	31	31
PDGFB-D/PDGFRB/GRB7/SHC	0.01	0.074	-9999	-0.31	17	17
SH2B2	0	0	-9999	-10000	0	0
PLCgamma1/SPHK1	-0.007	0.14	-9999	-0.51	22	22
LYN	-0.007	0.066	-9999	-0.38	11	11
LRP1	0.017	0.023	-9999	-0.52	1	1
SOS1	0.017	0.023	-9999	-0.52	1	1
STAT5B	0.016	0.026	-9999	-0.39	2	2
STAT5A	0.011	0.056	-9999	-0.42	8	8
NCK1-2/p130 Cas	0.033	0.062	-9999	-0.35	5	5
SPHK1	-0.027	0.14	-9999	-0.42	54	54
EDG1	-0.019	0.12	-9999	-0.4	46	46
mol:DAG	0.003	0.11	-9999	-0.64	11	11
PLCG1	0.003	0.11	-9999	-0.66	11	11
NHERF/PDGFRB	-0.038	0.15	-9999	-0.35	91	91
YES1	-0.016	0.096	-9999	-0.47	18	18
cell migration	-0.038	0.15	-9999	-0.35	91	91
SHC/Grb2/SOS1	0.036	0.06	-9999	-0.3	7	7
SLC9A3R2	-0.032	0.15	-9999	-0.49	52	52
SLC9A3R1	-0.043	0.16	-9999	-0.44	70	70
NHERF1-2/PDGFRB/PTEN	-0.033	0.16	-9999	-0.32	103	103
FYN	-0.017	0.14	-9999	-0.77	12	12
DOK1	0.013	0.074	-9999	-0.3	23	23
HRAS/GTP	0.009	0.036	-9999	-0.29	7	7
PDGFB	0.009	0.064	-9999	-0.39	12	12
RAC1	-0.011	0.16	-9999	-0.49	40	40
PRKCD	0.019	0.065	-9999	-0.32	14	14
FER	0.02	0.06	-9999	-0.3	13	13
MAPKKK cascade	-0.006	0.05	-9999	-0.34	4	4
RASA1	0.013	0.072	-9999	-0.29	22	22
NCK1	0.011	0.045	-9999	-0.28	12	12
NCK2	0.015	0.026	-9999	-0.25	5	5
p62DOK/Csk	0.023	0.071	-9999	-0.27	23	23
PDGFB-D/PDGFRB/SHB	0.013	0.071	-9999	-0.4	14	14
chemotaxis	-0.004	0.11	-9999	-0.47	17	17
STAT1-3-5/STAT1-3-5	-0.021	0.071	-9999	-0.4	6	6
Bovine Papilomavirus E5/PDGFRB	0.006	0.049	-9999	-0.39	8	8
PTPRJ	0.012	0.055	-9999	-0.44	7	7

×

Signaling events mediated by PRL

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
CCNE1	-0.018	0.099	-10000	0	-0.28	64	64
mol:Halofuginone	0.004	0.012	-10000	0	-10000	0	0
ITGA1	0	0.096	-10000	0	-0.51	18	18
CDKN1A	-0.017	0.12	-10000	0	-0.47	24	24
PRL-3/alpha Tubulin	0.024	0.026	-10000	0	-0.37	1	1
mol:Ca2+	-0.076	0.13	0.38	1	-0.26	156	157
AGT	-0.095	0.19	-10000	0	-0.36	158	158
CCNA2	-0.044	0.13	-10000	0	-0.68	4	4
TUBA1B	0.018	0	-10000	0	-10000	0	0
EGR1	-0.06	0.15	-10000	0	-0.37	82	82
CDK2/Cyclin E1	-0.016	0.12	-10000	0	-0.44	27	27
MAPK3	0.022	0.032	-10000	0	-0.37	2	2
PRL-2 /Rab GGTase beta	0.017	0.053	-10000	0	-0.37	8	8
MAPK1	0.021	0.035	-10000	0	-0.37	3	3
PTP4A1	-0.031	0.12	-10000	0	-0.66	4	4
PTP4A3	0.014	0.037	-10000	0	-0.29	7	7
PTP4A2	0.006	0.072	-10000	0	-0.4	15	15
ITGB1	0.02	0.041	-10000	0	-0.37	4	4
SRC	0.015	0.035	-10000	0	-0.43	3	3
RAC1	0.004	0.066	-10000	0	-0.57	2	2
Rab GGTase beta/Rab GGTase alpha	0.026	0.011	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.022	0.12	-10000	0	-0.61	4	4
RABGGTA	0.018	0	-10000	0	-10000	0	0
BCAR1	0.002	0.023	0.38	1	-10000	0	1
RHOC	0.001	0.075	-10000	0	-0.5	5	5
RHOA	-0.006	0.089	-10000	0	-0.42	14	14
cell motility	0.002	0.075	-10000	0	-0.49	3	3
PRL-1/alpha Tubulin	-0.02	0.12	-10000	0	-0.61	4	4
PRL-3/alpha1 Integrin	0.011	0.077	-10000	0	-0.39	17	17
ROCK1	0.002	0.075	-10000	0	-0.5	3	3
RABGGTB	0.017	0.017	-10000	0	-0.25	2	2
CDK2	0.012	0.047	-10000	0	-0.31	10	10
mitosis	-0.031	0.12	-10000	0	-0.65	4	4
ATF5	0.013	0.04	-10000	0	-0.28	9	9

×

EPHB forward 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
Ephrin A5/EPHB2	0.011	0.056	-10000	0	-0.3	12	12
cell-cell adhesion	0.038	0.084	0.37	18	-10000	0	18
Ephrin B/EPHB2/RasGAP	0.023	0.087	-10000	0	-0.28	32	32
ITSN1	0.015	0.035	-10000	0	-0.43	3	3
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
SHC1	0.017	0.023	-10000	0	-0.52	1	1
Ephrin B1/EPHB3	0.006	0.072	-10000	0	-0.32	21	21
Ephrin B1/EPHB1	-0.003	0.07	-10000	0	-0.3	13	13
HRAS/GDP	-0.034	0.081	-10000	0	-0.3	28	28
Ephrin B/EPHB1/GRB7	-0.003	0.097	-10000	0	-0.27	34	34
Endophilin/SYNJ1	0.018	0.065	-10000	0	-0.23	25	25
KRAS	0.009	0.065	-10000	0	-0.44	10	10
Ephrin B/EPHB1/Src	0.013	0.089	-10000	0	-0.28	26	26
endothelial cell migration	-0.006	0.11	-10000	0	-0.28	59	59
GRB2	0.016	0.024	-10000	0	-0.25	4	4
GRB7	-0.017	0.1	-10000	0	-0.29	59	59
PAK1	0.002	0.093	-10000	0	-0.35	8	8
HRAS	0.012	0.051	-10000	0	-0.41	7	7
RRAS	0.015	0.075	-10000	0	-0.25	32	32
DNM1	0.013	0.047	-10000	0	-0.37	7	7
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.005	0.079	-10000	0	-0.26	27	27
lamellipodium assembly	-0.038	0.084	-10000	0	-0.37	18	18
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.016	0.077	-10000	0	-0.47	5	5
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
EPHB2	0.007	0.061	-10000	0	-0.32	16	16
EPHB3	-0.005	0.1	-10000	0	-0.45	26	26
EPHB1	-0.022	0.1	-10000	0	-0.28	72	72
EPHB4	-0.013	0.12	-10000	0	-0.43	36	36
mol:GDP	0	0.1	-10000	0	-0.33	25	25
Ephrin B/EPHB2	0.019	0.07	-10000	0	-0.25	26	26
Ephrin B/EPHB3	0.012	0.086	-10000	0	-0.27	37	37
JNK cascade	0.006	0.082	-10000	0	-0.28	23	23
Ephrin B/EPHB1	0.005	0.084	-10000	0	-0.26	33	33
RAP1/GDP	0.013	0.099	-10000	0	-0.33	15	15
EFNB2	-0.008	0.11	-10000	0	-0.4	33	33
EFNB3	0.018	0	-10000	0	-10000	0	0
EFNB1	0.01	0.051	-10000	0	-0.3	13	13
Ephrin B2/EPHB1-2	-0.007	0.089	-10000	0	-0.28	34	34
RAP1B	0.013	0.044	-10000	0	-0.32	8	8
RAP1A	0.012	0.057	-10000	0	-0.52	6	6
CDC42/GTP	-0.031	0.076	-10000	0	-0.39	11	11
Rap1/GTP	-0.03	0.079	-10000	0	-0.4	14	14
axon guidance	0.011	0.056	-10000	0	-0.3	12	12
MAPK3	0.027	0.07	-10000	0	-0.42	5	5
MAPK1	0.027	0.071	-10000	0	-0.39	6	6
Rac1/GDP	0.01	0.095	-10000	0	-0.31	23	23
actin cytoskeleton reorganization	-0.035	0.074	-10000	0	-0.31	18	18
CDC42/GDP	0.01	0.095	-10000	0	-0.31	23	23
PI3K	-0.003	0.11	-10000	0	-0.28	59	59
EFNA5	0.006	0.068	-10000	0	-0.35	17	17
Ephrin B2/EPHB4	-0.01	0.1	-10000	0	-0.33	40	40
Ephrin B/EPHB2/Intersectin/N-WASP	0.02	0.069	-10000	0	-0.23	34	34
CDC42	0.018	0	-10000	0	-10000	0	0
RAS family/GTP	-0.035	0.077	-10000	0	-0.34	17	17
PTK2	0.006	0.034	-10000	0	-0.34	3	3
MAP4K4	0.006	0.083	-10000	0	-0.28	23	23
SRC	0.015	0.035	-10000	0	-0.43	3	3
KALRN	0.006	0.057	-10000	0	-0.27	21	21
Intersectin/N-WASP	0.019	0.054	-10000	0	-0.37	10	10
neuron projection morphogenesis	0.009	0.11	-10000	0	-0.34	22	22
MAP2K1	0.022	0.073	-10000	0	-0.44	5	5
WASL	0.01	0.066	-10000	0	-0.52	8	8
Ephrin B1/EPHB1-2/NCK1	0.011	0.081	-10000	0	-0.27	26	26
cell migration	0.026	0.077	-10000	0	-0.45	5	5
NRAS	0.005	0.076	-10000	0	-0.4	16	16
SYNJ1	0.019	0.066	-10000	0	-0.24	25	25
PXN	0.018	0	-10000	0	-10000	0	0
TF	0.019	0.066	-10000	0	-0.32	1	1
HRAS/GTP	0.004	0.092	-10000	0	-0.38	12	12
Ephrin B1/EPHB1-2	0.004	0.074	-10000	0	-0.27	22	22
cell adhesion mediated by integrin	0.012	0.062	0.26	22	-10000	0	22
RAC1	0.018	0	-10000	0	-10000	0	0
mol:GTP	0.008	0.097	-10000	0	-0.41	11	11
RAC1-CDC42/GTP	-0.034	0.08	-10000	0	-0.35	18	18
RASA1	0.004	0.078	-10000	0	-0.42	16	16
RAC1-CDC42/GDP	0.017	0.093	-10000	0	-0.34	9	9
ruffle organization	0.008	0.11	-10000	0	-0.38	17	17
NCK1	0.011	0.045	-10000	0	-0.28	12	12
receptor internalization	0.022	0.067	-10000	0	-0.32	2	2
Ephrin B/EPHB2/KALRN	0.024	0.078	-10000	0	-0.27	24	24
ROCK1	0.012	0.064	-10000	0	-0.28	21	21
RAS family/GDP	-0.035	0.077	-10000	0	-0.33	17	17
Rac1/GTP	-0.039	0.089	-10000	0	-0.39	18	18
Ephrin B/EPHB1/Src/Paxillin	0.013	0.077	-10000	0	-0.49	4	4

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	0.015	0.029	-9999	-0.25	6	6
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.018	0	-9999	-10000	0	0
TCEB1	0.014	0.035	-9999	-0.3	6	6
HIF1A/p53	-0.02	0.11	-9999	-0.32	39	39
HIF1A	-0.011	0.087	-9999	-0.32	20	20
COPS5	0.01	0.056	-9999	-0.35	11	11
VHL/Elongin B/Elongin C/RBX1/CUL2	0.049	0.025	-9999	-0.24	1	1
FIH (dimer)	0.017	0.023	-9999	-0.52	1	1
CDKN2A	-0.053	0.15	-9999	-0.33	108	108
ARNT/IPAS	0.024	0.02	-9999	-10000	0	0
HIF1AN	0.017	0.023	-9999	-0.52	1	1
GNB2L1	0.015	0.04	-9999	-0.52	3	3
HIF1A/ARNT	0	0.084	-9999	-0.3	20	20
CUL2	0.017	0.017	-9999	-0.25	2	2
OS9	0.014	0.04	-9999	-0.34	6	6
RACK1/Elongin B/Elongin C	0.032	0.033	-9999	-0.3	4	4
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.002	0.089	-9999	-0.32	20	20
PHD1-3/OS9	-0.021	0.12	-9999	-0.29	76	76
HIF1A/RACK1/Elongin B/Elongin C	0.013	0.083	-9999	-0.27	18	18
VHL	0.015	0.029	-9999	-0.25	6	6
HSP90AA1	0.013	0.045	-9999	-0.39	6	6
HIF1A/JAB1	-0.004	0.087	-9999	-0.29	22	22
EGLN3	-0.074	0.18	-9999	-0.4	116	116
EGLN2	0.011	0.053	-9999	-0.37	9	9
EGLN1	0.001	0.082	-9999	-0.35	24	24
TP53	-0.023	0.14	-9999	-0.48	43	43
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.034	0.033	-9999	-0.5	1	1
ARNT	0.018	0	-9999	-10000	0	0
ARD1A	0.016	0.02	-9999	-0.25	3	3
RBX1	0.018	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.032	0.11	-9999	-0.32	36	36

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.001	0.073	-9999	-0.26	34	34
TRAF2/ASK1	-0.002	0.085	-9999	-0.31	33	33
ATM	0.017	0.012	-9999	-0.25	1	1
MAP2K3	-0.011	0.12	-9999	-0.38	37	37
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.016	0.12	-9999	-0.33	40	40
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.003	0.083	-9999	-0.45	16	16
TXN	0.009	0.007	-9999	-10000	0	0
CALM1	0.018	0	-9999	-10000	0	0
GADD45A	-0.011	0.11	-9999	-0.39	38	38
GADD45B	-0.002	0.097	-9999	-0.44	23	23
MAP3K1	-0.03	0.14	-9999	-0.42	58	58
MAP3K6	0.015	0.035	-9999	-0.43	3	3
MAP3K7	0.016	0.02	-9999	-0.25	3	3
MAP3K4	0.018	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	-0.004	0.099	-9999	-0.37	33	33
TAK1/TAB family	0.01	0.038	-9999	-0.42	4	4
RAC1/OSM/MEKK3	0.034	0.006	-9999	-10000	0	0
TRAF2	0.014	0.042	-9999	-0.45	4	4
RAC1/OSM/MEKK3/MKK3	-0.029	0.079	-9999	-0.28	37	37
TRAF6	0.017	0.033	-9999	-0.32	5	5
RAC1	0.018	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.078	0.18	-9999	-0.36	133	133
CCM2	0.018	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.034	0.11	-9999	-0.31	55	55
MAPK11	0.018	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.04	0.12	-9999	-0.29	87	87
OSM/MEKK3	0.026	0.008	-9999	-10000	0	0
TAOK1	0.012	0.044	-9999	-0.32	7	7
TAOK2	0.02	0.005	-9999	-10000	0	0
TAOK3	0.019	0.016	-9999	-0.32	1	1
MAP3K7IP1	0.018	0	-9999	-10000	0	0
MAPK14	0.017	0.012	-9999	-0.25	1	1
MAP3K7IP2	0.014	0.047	-9999	-0.52	4	4
MAP3K5	-0.022	0.13	-9999	-0.42	47	47
MAP3K10	-0.001	0.097	-9999	-0.48	20	20
MAP3K3	0.017	0.012	-9999	-0.25	1	1
TRX/ASK1	-0.003	0.079	-9999	-0.31	30	30
GADD45/MTK1/MTK1	0.009	0.097	-9999	-0.29	42	42

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.018	0	-9999	-10000	0	0
VLDLR	-0.061	0.17	-9999	-0.4	100	100
LRPAP1	0.016	0.026	-9999	-0.39	2	2
NUDC	0.018	0	-9999	-10000	0	0
RELN/LRP8	-0.015	0.1	-9999	-0.31	43	43
CaM/Ca2+	0.013	0	-9999	-10000	0	0
KATNA1	0.015	0.033	-9999	-0.31	5	5
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.008	0.093	-9999	-0.28	43	43
IQGAP1/CaM	0.026	0	-9999	-10000	0	0
DAB1	0.018	0	-9999	-10000	0	0
IQGAP1	0.018	0	-9999	-10000	0	0
PLA2G7	-0.092	0.2	-9999	-0.41	137	137
CALM1	0.018	0	-9999	-10000	0	0
DYNLT1	0.018	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.027	0.11	-9999	-0.37	37	37
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.015	0.037	-9999	-0.39	4	4
CDK5R1	0.014	0.031	-9999	-0.25	7	7
LIS1/Poliovirus Protein 3A	0.018	0.02	-9999	-0.31	2	2
CDK5R2	0.017	0.017	-9999	-0.25	2	2
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.017	0.11	-9999	-0.31	59	59
YWHAE	0.016	0.029	-9999	-0.34	3	3
NDEL1/14-3-3 E	0.024	0.079	-9999	-0.29	4	4
MAP1B	-0.015	0.075	-9999	-0.29	34	34
RAC1	0.024	0.01	-9999	-10000	0	0
p35/CDK5	0.007	0.085	-9999	-0.33	3	3
RELN	0.01	0.059	-9999	-0.38	11	11
PAFAH/LIS1	-0.036	0.12	-9999	-0.3	80	80
LIS1/CLIP170	0.029	0.031	-9999	-0.3	4	4
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.016	0.043	-9999	-0.29	1	1
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	0.002	0.096	-9999	-0.45	3	3
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	0.016	0.08	-9999	-0.31	3	3
LIS1/IQGAP1	0.031	0.021	-9999	-0.3	2	2
RHOA	0.014	0.067	-9999	-0.42	12	12
PAFAH1B1	0.024	0.024	-9999	-0.37	2	2
PAFAH1B3	0.009	0.067	-9999	-0.49	9	9
PAFAH1B2	0.017	0.012	-9999	-0.25	1	1
MAP1B/LIS1/Dynein heavy chain	0.013	0.055	-9999	-0.31	2	2
NDEL1/Katanin 60/Dynein heavy chain	0.031	0.078	-9999	-10000	0	0
LRP8	-0.057	0.16	-9999	-0.34	110	110
NDEL1/Katanin 60	0.024	0.079	-9999	-0.29	3	3
P39/CDK5	0.008	0.084	-9999	-0.33	3	3
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.031	0.021	-9999	-0.3	2	2
CDK5	-0.001	0.087	-9999	-0.25	43	43
PPP2R5D	0.016	0.02	-9999	-0.25	3	3
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.025	0.026	-9999	-0.26	4	4
CSNK2A1	0.017	0.023	-9999	-0.52	1	1
RELN/VLDLR/DAB1/LIS1	0.003	0.1	-9999	-0.25	59	59
RELN/VLDLR	-0.045	0.14	-9999	-0.28	113	113
CDC42	0.024	0.01	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0.023	-9999	-0.52	1	1
HDAC2	0.009	0.053	-9999	-0.29	15	15
GNB1/GNG2	-0.008	0.11	-9999	-0.31	55	55
forebrain development	0.005	0.14	-9999	-0.54	18	18
GNAO1	0.017	0.024	-9999	-0.25	4	4
SMO/beta Arrestin2	-0.018	0.12	-9999	-0.37	49	49
SMO	-0.047	0.16	-9999	-0.41	82	82
ARRB2	0.019	0.001	-9999	-10000	0	0
GLI3/SPOP	0.011	0.13	-9999	-0.43	21	21
mol:GTP	0.001	0.001	-9999	-10000	0	0
GSK3B	0.018	0	-9999	-10000	0	0
GNAI2	0.007	0.075	-9999	-0.48	12	12
SIN3/HDAC complex	0.041	0.032	-9999	-0.27	5	5
GNAI1	-0.016	0.12	-9999	-0.38	46	46
XPO1	0.021	0.003	-9999	-10000	0	0
GLI1/Su(fu)	-0.006	0.17	-9999	-0.58	25	25
SAP30	0.012	0.053	-9999	-0.48	6	6
mol:GDP	-0.047	0.16	-9999	-0.41	82	82
MIM/GLI2A	-0.022	0.14	-9999	-0.4	61	61
IFT88	-0.001	0.097	-9999	-0.48	20	20
GNAI3	0.019	0.001	-9999	-10000	0	0
GLI2	0.035	0.055	-9999	-0.41	1	1
GLI3	0.004	0.14	-9999	-0.38	29	29
CSNK1D	0.018	0	-9999	-10000	0	0
CSNK1E	0.017	0.012	-9999	-0.25	1	1
SAP18	0.017	0	-9999	-10000	0	0
embryonic digit morphogenesis	-0.001	0.097	-9999	-0.48	20	20
GNG2	0.016	0.029	-9999	-0.34	3	3
Gi family/GTP	-0.008	0.12	-9999	-0.38	25	25
SIN3B	0.017	0.012	-9999	-0.25	1	1
SIN3A	0.017	0	-9999	-10000	0	0
GLI3/Su(fu)	0.009	0.14	-9999	-0.43	35	35
GLI2/Su(fu)	0.026	0.1	-9999	-0.34	15	15
FOXA2	-0.051	0.18	-9999	-0.73	34	34
neural tube patterning	0.005	0.14	-9999	-0.54	18	18
SPOP	0.013	0.042	-9999	-0.33	7	7
Su(fu)/PIAS1	0.004	0.093	-9999	-0.34	21	21
GNB1	0.013	0.052	-9999	-0.52	5	5
CSNK1G2	0.016	0.033	-9999	-0.52	2	2
CSNK1G3	0.013	0.052	-9999	-0.52	5	5
MTSS1	-0.023	0.14	-9999	-0.4	61	61
embryonic limb morphogenesis	0.005	0.14	-9999	-0.54	18	18
SUFU	-0.006	0.1	-9999	-0.38	21	21
LGALS3	-0.041	0.16	-9999	-0.48	63	63
catabolic process	0.031	0.12	-9999	-0.37	22	22
GLI3A/CBP	0.006	0.07	-9999	-0.36	10	10
KIF3A	0.007	0.074	-9999	-0.5	11	11
GLI1	0.005	0.14	-9999	-0.56	18	18
RAB23	0.008	0.065	-9999	-0.38	13	13
CSNK1A1	0.017	0.023	-9999	-0.52	1	1
IFT172	0.013	0.049	-9999	-0.43	6	6
RBBP7	0.01	0.051	-9999	-0.3	13	13
Su(fu)/Galectin3	-0.028	0.14	-9999	-0.34	71	71
GNAZ	0.002	0.088	-9999	-0.44	19	19
RBBP4	0.016	0.026	-9999	-0.39	2	2
CSNK1G1	0.017	0.012	-9999	-0.25	1	1
PIAS1	0.017	0.012	-9999	-0.25	1	1
PRKACA	0.018	0	-9999	-10000	0	0
GLI2/SPOP	0.04	0.057	-9999	-0.39	2	2
STK36	0	0.11	-9999	-0.52	21	21
Gi family/GNB1/GNG2/GDP	0	0.11	-9999	-0.36	28	28
PTCH1	0.014	0.13	-9999	-0.66	7	7
MIM/GLI1	0	0.16	-9999	-0.54	21	21
CREBBP	0.006	0.07	-9999	-0.36	10	10
Su(fu)/SIN3/HDAC complex	0.036	0.047	-9999	-0.26	1	1

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.009	0.13	-10000	0	-0.51	12	12
BAG4	0.002	0.07	-10000	0	-0.28	28	28
BAD	0.012	0.045	-10000	0	-0.18	9	9
NFKBIA	0.014	0.042	-10000	0	-0.45	4	4
BIRC3	-0.085	0.19	-10000	0	-0.41	128	128
BAX	0.011	0.045	-10000	0	-0.19	7	7
EnzymeConsortium:3.1.4.12	0.002	0.03	-10000	0	-0.11	12	12
IKBKB	-0.003	0.12	-10000	0	-0.44	16	16
MAP2K2	0.023	0.046	-10000	0	-0.24	6	6
MAP2K1	0.024	0.043	-10000	0	-0.23	4	4
SMPD1	0.006	0.039	-10000	0	-0.19	9	9
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.002	0.12	-10000	0	-0.42	19	19
MAP2K4	-0.011	0.089	-10000	0	-0.24	55	55
protein ubiquitination	-0.003	0.12	-10000	0	-0.46	14	14
EnzymeConsortium:2.7.1.37	0.02	0.052	-10000	0	-0.26	4	4
response to UV	0	0	-10000	0	-0.002	4	4
RAF1	0.018	0.044	-10000	0	-0.22	4	4
CRADD	0.01	0.063	-10000	0	-0.49	8	8
mol:ceramide	0.005	0.046	-10000	0	-0.17	13	13
I-kappa-B-alpha/RELA/p50/ubiquitin	0.022	0.026	-10000	0	-0.31	3	3
MADD	0.018	0	-10000	0	-10000	0	0
MAP3K1	-0.009	0.083	-10000	0	-0.24	44	44
TRADD	0.016	0.026	-10000	0	-0.39	2	2
RELA/p50	0.018	0	-10000	0	-10000	0	0
MAPK3	0.027	0.044	-10000	0	-0.22	3	3
MAPK1	0.026	0.044	-10000	0	-0.22	3	3
p50/RELA/I-kappa-B-alpha	0.024	0.031	-10000	0	-0.37	3	3
FADD	-0.011	0.13	-10000	0	-0.44	19	19
KSR1	0.012	0.045	-10000	0	-0.19	7	7
MAPK8	-0.004	0.086	-10000	0	-0.24	37	37
TRAF2	0.014	0.042	-10000	0	-0.45	4	4
response to radiation	0	0	-10000	0	-0.002	1	1
CHUK	-0.007	0.13	-10000	0	-0.46	16	16
TNF R/SODD	0.014	0.054	-10000	0	-0.37	5	5
TNF	-0.004	0.094	-10000	0	-0.36	31	31
CYCS	0.036	0.056	0.14	65	-0.17	5	70
IKBKG	-0.001	0.12	-10000	0	-0.47	12	12
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.011	0.13	-10000	0	-0.55	11	11
RELA	0.018	0	-10000	0	-10000	0	0
RIPK1	0.017	0.023	-10000	0	-0.52	1	1
AIFM1	0.037	0.056	0.14	65	-0.17	5	70
TNF/TNF R/SODD	0.012	0.074	-10000	0	-0.31	18	18
TNFRSF1A	0.016	0.033	-10000	0	-0.52	2	2
response to heat	0	0	-10000	0	-0.002	1	1
CASP8	0.021	0.032	-10000	0	-10000	0	0
NSMAF	-0.007	0.13	-10000	0	-0.48	14	14
response to hydrogen peroxide	0	0	-10000	0	-0.002	4	4
BCL2	-0.11	0.22	-10000	0	-0.47	144	144

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.023	0.016	-9999	-0.31	1	1
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.017	0.023	-9999	-0.52	1	1
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.011	0.11	-9999	-0.4	37	37
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	-0.006	0.1	-9999	-0.38	31	31
RAC1-CDC42/GTP/PAK family	-0.001	0.072	-9999	-0.22	41	41
response to UV	0	0	-9999	-10000	0	0
YES1	0.007	0.07	-9999	-0.43	12	12
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.017	0.012	-9999	-0.25	1	1
FYN	0.008	0.067	-9999	-0.41	12	12
MAP3K12	0.018	0	-9999	-10000	0	0
FGR	0.017	0.017	-9999	-0.25	2	2
p38 alpha/TAB1	0.01	0.094	-9999	-0.28	29	29
PRKG1	0.017	0.012	-9999	-0.25	1	1
DUSP8	-0.005	0.1	-9999	-0.48	24	24
PGK/cGMP/p38 alpha	-0.028	0.071	-9999	-0.26	32	32
apoptosis	0.009	0.09	-9999	-0.27	30	30
RAL/GTP	0.022	0.029	-9999	-0.31	4	4
LYN	0.014	0.031	-9999	-0.25	7	7
DUSP1	-0.038	0.15	-9999	-0.41	69	69
PAK1	-0.022	0.13	-9999	-0.37	54	54
SRC	0.015	0.035	-9999	-0.43	3	3
RAC1/OSM/MEKK3/MKK3	0.043	0.021	-9999	-0.27	1	1
TRAF6	0.017	0.023	-9999	-0.52	1	1
RAC1	0.018	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.018	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.024	0	-9999	-10000	0	0
MAPK11	0.002	0.11	-9999	-0.32	34	34
BLK	-0.019	0.1	-9999	-0.29	63	63
HCK	-0.005	0.11	-9999	-0.47	25	25
MAP2K3	0.014	0.037	-9999	-0.29	7	7
DUSP16	0.005	0.078	-9999	-0.43	15	15
DUSP10	-0.017	0.12	-9999	-0.39	44	44
TRAF6/MEKK3	0.022	0.015	-9999	-0.28	1	1
MAP3K7IP1	0.018	0	-9999	-10000	0	0
MAPK14	0.003	0.1	-9999	-0.3	33	33
positive regulation of innate immune response	0.002	0.12	-9999	-0.37	31	31
LCK	-0.074	0.18	-9999	-0.4	117	117
p38alpha-beta/MKP7	0.006	0.13	-9999	-0.36	36	36
p38alpha-beta/MKP5	-0.003	0.13	-9999	-0.35	40	40
PGK/cGMP	0.013	0.008	-9999	-0.17	1	1
PAK2	0.018	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.013	0.14	-9999	-0.36	45	45
CDC42	0.018	0	-9999	-10000	0	0
RALB	0.014	0.047	-9999	-0.52	4	4
RALA	0.018	0	-9999	-10000	0	0
PAK3	-0.033	0.13	-9999	-0.32	80	80

×

S1P3 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.01	0.066	-9999	-0.52	8	8
mol:S1P	0	0.005	-9999	-0.015	43	43
S1P1/S1P/Gi	0	0.1	-9999	-0.4	16	16
GNAO1	0.016	0.024	-9999	-0.25	4	4
S1P/S1P3/G12/G13	0.02	0.031	-9999	-0.29	4	4
AKT1	0.012	0.097	-9999	-0.58	12	12
AKT3	0.004	0.14	-9999	-1.2	4	4
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.01	0.066	-9999	-0.52	8	8
GNAI2	0.007	0.075	-9999	-0.48	12	12
GNAI3	0.018	0.004	-9999	-10000	0	0
GNAI1	-0.016	0.12	-9999	-0.38	46	46
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.001	0.005	-9999	-0.017	43	43
S1PR2	0	0	-9999	-10000	0	0
EDG1	-0.019	0.12	-9999	-0.4	46	46
mol:Ca2+	0.01	0.081	-9999	-0.29	15	15
MAPK3	0.016	0.078	-9999	-0.34	8	8
MAPK1	0.016	0.078	-9999	-0.33	9	9
JAK2	0.006	0.095	-9999	-0.34	19	19
CXCR4	-0.006	0.11	-9999	-0.31	42	42
FLT1	0.006	0.08	-9999	-0.45	15	15
RhoA/GDP	0.004	0.058	-9999	-0.38	12	12
Rac1/GDP	0.013	0	-9999	-10000	0	0
SRC	0.015	0.08	-9999	-0.36	9	9
S1P/S1P3/Gi	0.01	0.082	-9999	-0.3	15	15
RAC1	0.018	0	-9999	-10000	0	0
RhoA/GTP	0.011	0.087	-9999	-0.3	18	18
VEGFA	0.001	0.076	-9999	-0.29	31	31
S1P/S1P2/Gi	0.009	0.076	-9999	-0.29	14	14
VEGFR1 homodimer/VEGFA homodimer	0.01	0.083	-9999	-0.39	15	15
RHOA	0.005	0.08	-9999	-0.52	12	12
S1P/S1P3/Gq	-0.027	0.094	-9999	-0.27	58	58
GNAQ	0	0	-9999	-10000	0	0
GNAZ	0.002	0.088	-9999	-0.44	19	19
G12/G13	0.021	0.039	-9999	-0.37	4	4
GNA14	-0.079	0.18	-9999	-0.35	140	140
GNA15	0.002	0.076	-9999	-0.34	23	23
GNA12	0.018	0	-9999	-10000	0	0
GNA13	0.011	0.055	-9999	-0.36	10	10
GNA11	0.014	0.047	-9999	-0.52	4	4
Rac1/GTP	0.018	0.075	-9999	-0.34	7	7

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.015	0.034	-10000	0	-0.32	4	4
RAS family/GTP	0.002	0.099	-10000	0	-0.33	22	22
NFATC4	0.007	0.079	-10000	0	-0.32	11	11
ERBB2IP	0.017	0.023	-10000	0	-0.52	1	1
HSP90 (dimer)	0.013	0.045	-10000	0	-0.39	6	6
mammary gland morphogenesis	-0.01	0.094	-10000	0	-0.33	18	18
JUN	0.02	0.072	-10000	0	-10000	0	0
HRAS	0.012	0.051	-10000	0	-0.41	7	7
DOCK7	-0.002	0.092	-10000	0	-0.39	10	10
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.013	0.1	-10000	0	-0.3	47	47
AKT1	0.008	0.038	-10000	0	-0.26	9	9
BAD	0.016	0.035	-10000	0	-0.31	5	5
MAPK10	0.003	0.069	-10000	0	-0.22	18	18
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.01	0.1	-10000	0	-0.36	18	18
RAF1	0.006	0.1	-10000	0	-0.34	20	20
ErbB2/ErbB3/neuregulin 2	-0.037	0.12	-10000	0	-0.34	57	57
STAT3	0.016	0.095	-10000	0	-0.95	5	5
cell migration	0.009	0.07	-10000	0	-0.21	16	16
mol:PI-3-4-5-P3	0	0.002	-10000	0	-10000	0	0
cell proliferation	-0.045	0.24	-10000	0	-0.62	54	54
FOS	-0.059	0.22	-10000	0	-0.45	106	106
NRAS	0.005	0.076	-10000	0	-0.4	16	16
mol:Ca2+	-0.01	0.094	-10000	0	-0.33	18	18
MAPK3	-0.021	0.19	-10000	0	-0.47	53	53
MAPK1	-0.021	0.19	-10000	0	-0.47	53	53
JAK2	-0.004	0.096	-10000	0	-0.39	13	13
NF2	0.003	0.01	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.001	0.082	-10000	0	-0.27	39	39
NRG1	0.007	0.053	-10000	0	-0.27	18	18
GRB2/SOS1	0.024	0.023	-10000	0	-0.37	1	1
MAPK8	-0.001	0.089	-10000	0	-0.29	22	22
MAPK9	0.008	0.067	-10000	0	-0.23	15	15
ERBB2	-0.03	0.082	-10000	0	-0.39	15	15
ERBB3	-0.019	0.14	-10000	0	-0.52	36	36
SHC1	0.016	0.023	-10000	0	-0.52	1	1
RAC1	0.018	0	-10000	0	-10000	0	0
apoptosis	-0.01	0.041	0.35	5	-10000	0	5
STAT3 (dimer)	0.016	0.093	-10000	0	-0.93	5	5
RNF41	0.02	0.031	-10000	0	-0.28	4	4
FRAP1	0.016	0.032	-10000	0	-0.31	4	4
RAC1-CDC42/GTP	-0.022	0.055	-10000	0	-0.27	10	10
ErbB2/ErbB2/HSP90 (dimer)	-0.015	0.074	-10000	0	-0.32	18	18
CHRNA1	-0.008	0.16	-10000	0	-0.43	34	34
myelination	0.014	0.079	-10000	0	-0.32	11	11
PPP3CB	-0.001	0.086	-10000	0	-0.37	9	9
KRAS	0.009	0.065	-10000	0	-0.44	10	10
RAC1-CDC42/GDP	0.021	0.074	-10000	0	-0.29	10	10
NRG2	-0.017	0.1	-10000	0	-0.3	57	57
mol:GDP	0.001	0.082	-10000	0	-0.27	39	39
SOS1	0.017	0.023	-10000	0	-0.52	1	1
MAP2K2	0.006	0.11	-10000	0	-0.35	21	21
SRC	0.015	0.035	-10000	0	-0.43	3	3
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	0	0.091	-10000	0	-0.4	9	9
MAP2K1	-0.024	0.17	-10000	0	-0.44	38	38
heart morphogenesis	-0.01	0.094	-10000	0	-0.33	18	18
RAS family/GDP	0.013	0.099	-10000	0	-0.34	18	18
GRB2	0.015	0.024	-10000	0	-0.25	4	4
PRKACA	-0.001	0.005	-10000	0	-10000	0	0
CHRNE	0.016	0.019	-10000	0	-10000	0	0
HSP90AA1	0.013	0.045	-10000	0	-0.39	6	6
activation of caspase activity	-0.008	0.038	0.26	9	-10000	0	9
nervous system development	-0.01	0.094	-10000	0	-0.33	18	18
CDC42	0.018	0	-10000	0	-10000	0	0

×

BARD1 signaling events

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
BARD1/CSTF1	0.021	0.042	-10000	0	-0.37	5	5
ATM	0.017	0.012	-10000	0	-0.25	1	1
UBE2D3	0.018	0	-10000	0	-10000	0	0
PRKDC	0.012	0.045	-10000	0	-0.31	9	9
ATR	0.017	0.012	-10000	0	-0.25	1	1
UBE2L3	0.018	0	-10000	0	-10000	0	0
FANCD2	0.029	0.012	-10000	0	-10000	0	0
protein ubiquitination	0.016	0.083	-10000	0	-0.28	26	26
XRCC5	0.018	0	-10000	0	-10000	0	0
XRCC6	0.017	0.012	-10000	0	-0.25	1	1
M/R/N Complex	0.03	0.045	-10000	0	-0.3	9	9
MRE11A	0.018	0	-10000	0	-10000	0	0
DNA-PK	0.032	0.028	-10000	0	-0.3	2	2
FA complex/FANCD2/Ubiquitin	0.028	0.075	-10000	0	-0.37	6	6
FANCF	0.012	0.057	-10000	0	-0.52	6	6
BRCA1	0	0.094	-10000	0	-0.48	19	19
CCNE1	-0.018	0.099	-10000	0	-0.28	64	64
CDK2/Cyclin E1	-0.002	0.08	-10000	0	-0.37	11	11
FANCG	0.016	0.024	-10000	0	-0.25	4	4
BRCA1/BACH1/BARD1	0.01	0.076	-10000	0	-0.37	20	20
FANCE	0.006	0.061	-10000	0	-0.3	19	19
FANCC	0.013	0.042	-10000	0	-0.33	7	7
NBN	0.015	0.035	-10000	0	-0.43	3	3
FANCA	-0.032	0.12	-10000	0	-0.31	80	80
DNA repair	0.012	0.12	-10000	0	-0.38	25	25
BRCA1/BARD1/ubiquitin	0.01	0.076	-10000	0	-0.37	20	20
BARD1/DNA-PK	0.04	0.038	-10000	0	-0.27	6	6
FANCL	0.014	0.031	-10000	0	-0.25	7	7
mRNA polyadenylation	-0.021	0.042	0.37	5	-10000	0	5
BRCA1/BARD1/CTIP/M/R/N Complex	0.026	0.057	-10000	0	-0.32	2	2
BRCA1/BACH1/BARD1/TopBP1	0.022	0.068	-10000	0	-0.31	20	20
BRCA1/BARD1/P53	0.01	0.11	-10000	0	-0.3	51	51
BARD1/CSTF1/BRCA1	0.02	0.069	-10000	0	-0.3	21	21
BRCA1/BACH1	0	0.094	-10000	0	-0.48	19	19
BARD1	0.014	0.047	-10000	0	-0.52	4	4
PCNA	0.009	0.064	-10000	0	-0.39	12	12
BRCA1/BARD1/UbcH5C	0.022	0.066	-10000	0	-0.3	20	20
BRCA1/BARD1/UbcH7	0.022	0.066	-10000	0	-0.3	20	20
BRCA1/BARD1/RAD51/PCNA	-0.006	0.12	-10000	0	-0.28	74	74
BARD1/DNA-PK/P53	0.025	0.085	-10000	0	-0.25	43	43
BRCA1/BARD1/Ubiquitin	0.01	0.076	-10000	0	-0.37	20	20
BRCA1/BARD1/CTIP	0.015	0.081	-10000	0	-0.28	32	32
FA complex	0.017	0.073	-10000	0	-0.34	6	6
BARD1/EWS	0.023	0.034	-10000	0	-0.37	4	4
RBBP8	0.007	0.07	-10000	0	-0.37	12	12
TP53	-0.023	0.14	-10000	0	-0.48	43	43
TOPBP1	0.017	0.017	-10000	0	-0.25	2	2
G1/S transition of mitotic cell cycle	-0.008	0.11	0.3	51	-10000	0	51
BRCA1/BARD1	0.02	0.085	-10000	0	-0.28	26	26
CSTF1	0.014	0.035	-10000	0	-0.3	6	6
BARD1/EWS-Fli1	0.01	0.034	-10000	0	-0.38	4	4
CDK2	0.012	0.047	-10000	0	-0.31	10	10
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.041	0.16	-10000	0	-0.47	64	64
RAD50	0.011	0.062	-10000	0	-0.52	7	7
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.01	0.076	-10000	0	-0.37	20	20
EWSR1	0.018	0	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.02	0.089	-9999	-0.3	33	33
MAP4K1	0.012	0.04	-9999	-0.25	12	12
MAP3K8	-0.036	0.15	-9999	-0.39	70	70
PRKCB	0	0	-9999	-10000	0	0
DBNL	0.014	0.039	-9999	-0.36	5	5
CRKL	0.014	0.047	-9999	-0.52	4	4
MAP3K1	0.006	0.099	-9999	-0.35	12	12
JUN	-0.008	0.092	-9999	-0.33	19	19
MAP3K7	0.029	0.065	-9999	-0.28	6	6
GRAP2	0.012	0.042	-9999	-0.28	10	10
CRK	0.016	0.033	-9999	-0.52	2	2
MAP2K4	0.006	0.094	-9999	-0.35	15	15
LAT	0.002	0.068	-9999	-0.27	29	29
LCP2	-0.004	0.097	-9999	-0.4	27	27
MAPK8	0.011	0.052	-9999	-0.58	3	3
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.024	0.069	-9999	-0.3	6	6
LAT/GRAP2/SLP76/HPK1/HIP-55	0.026	0.087	-9999	-0.3	27	27

×

Signaling events mediated by HDAC Class III

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
EP300	0.014	0.047	-10000	0	-0.52	4	4
HDAC4	0.017	0.023	-10000	0	-0.52	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.011	0.027	0.24	3	-10000	0	3
CDKN1A	-0.018	0.13	-10000	0	-0.71	16	16
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.016	0.02	-10000	0	-0.25	3	3
FOXO3	0.001	0.043	0.41	4	-0.25	4	8
FOXO1	0	0.092	-10000	0	-0.46	19	19
FOXO4	0.022	0.034	-10000	0	-0.27	7	7
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.017	0.012	-10000	0	-0.25	1	1
TAT	-0.007	0.078	-10000	0	-0.25	48	48
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.011	0.091	-10000	0	-0.34	36	36
PPARGC1A	-0.012	0.1	-10000	0	-0.31	48	48
FHL2	-0.077	0.19	-10000	0	-0.41	117	117
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.024	0.029	-10000	0	-0.37	1	1
HIST2H4A	0.011	0.027	-10000	0	-0.24	3	3
SIRT1/FOXO3a	0.005	0.041	0.32	4	-0.2	5	9
SIRT1	0.016	0.04	0.2	10	-0.35	3	13
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.034	0.029	-10000	0	-0.31	2	2
SIRT1/Histone H1b	0.004	0.072	-10000	0	-0.23	38	38
apoptosis	-0.033	0.028	0.31	1	-10000	0	1
SIRT1/PGC1A	0.005	0.064	-10000	0	-0.32	11	11
p53/SIRT1	-0.016	0.11	0.4	10	-0.37	32	42
SIRT1/FOXO4	0.027	0.038	-10000	0	-0.24	7	7
FOXO1/FHL2/SIRT1	-0.03	0.12	-10000	0	-0.3	79	79
HIST1H1E	-0.005	0.08	-10000	0	-0.27	39	39
SIRT1/p300	0.022	0.043	-10000	0	-0.36	5	5
muscle cell differentiation	0.002	0.081	0.31	30	-10000	0	30
TP53	-0.022	0.14	-10000	0	-0.47	43	43
KU70/SIRT1/BAX	0.033	0.028	-10000	0	-0.31	1	1
CREBBP	0.016	0.033	-10000	0	-0.52	2	2
MEF2D	0.018	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.008	0.06	-10000	0	-0.37	1	1
ACSS2	0.023	0.029	-10000	0	-0.37	1	1
SIRT1/PCAF/MYOD	-0.002	0.081	-10000	0	-0.32	30	30

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.017	0.023	-10000	0	-0.52	1	1
HDAC3	0.018	0	-10000	0	-10000	0	0
VDR	-0.003	0.1	-10000	0	-0.51	21	21
Cbp/p300/PCAF	0.02	0.036	-10000	0	-0.31	6	6
EP300	0.014	0.047	-10000	0	-0.52	4	4
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.022	0.059	-10000	0	-0.28	3	3
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.017	0.012	-10000	0	-0.25	1	1
AKT1	0.03	0.093	0.22	54	-0.24	20	74
RAR alpha/9cRA/Cyclin H	-0.024	0.062	-10000	0	-0.4	5	5
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.014	0.07	-10000	0	-0.29	9	9
CDC2	-0.012	0.12	-10000	0	-0.44	34	34
response to UV	-0.002	0.009	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.015	0.049	-10000	0	-0.37	5	5
NCOR2	0.018	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.075	-10000	0	-0.37	21	21
RXRs/RARs/NRIP1/9cRA	-0.009	0.19	-10000	0	-0.54	53	53
NCOA2	0.009	0.063	-10000	0	-0.4	11	11
NCOA3	0.013	0.047	-10000	0	-0.37	7	7
NCOA1	0.012	0.057	-10000	0	-0.52	6	6
VDR/VDR/DNA	-0.003	0.1	-10000	0	-0.51	21	21
RARG	0.016	0.024	-10000	0	-0.52	1	1
RAR gamma1/9cRA	0.022	0.016	-10000	0	-0.31	1	1
MAPK3	0.015	0.027	-10000	0	-0.39	2	2
MAPK1	0.016	0.033	-10000	0	-0.52	2	2
MAPK8	0.013	0.041	-10000	0	-0.52	3	3
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.002	0.12	-10000	0	-0.46	10	10
RARA	0.019	0.047	-10000	0	-0.25	8	8
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.014	0.067	-10000	0	-0.26	7	7
PRKCA	0.011	0.038	-10000	0	-0.26	8	8
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.026	0.21	-10000	0	-0.6	54	54
RXRG	0.014	0.063	-10000	0	-0.33	12	12
RXRA	0.011	0.08	-10000	0	-0.33	5	5
RXRB	0.021	0.041	-10000	0	-0.3	3	3
VDR/Vit D3/DNA	-0.002	0.075	-10000	0	-0.37	21	21
RBP1	-0.076	0.19	-10000	0	-0.42	112	112
CRBP1/9-cic-RA	-0.053	0.14	-10000	0	-0.3	112	112
RARB	-0.025	0.13	-10000	0	-0.36	60	60
PRKCG	0.016	0.017	-10000	0	-10000	0	0
MNAT1	0.017	0.012	-10000	0	-0.25	1	1
RAR alpha/RXRs	0.02	0.15	-10000	0	-0.43	18	18
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.023	0.11	-10000	0	-0.33	14	14
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.064	-10000	0	-0.27	4	4
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.026	0.21	-10000	0	-0.6	54	54
positive regulation of DNA binding	-0.023	0.059	-10000	0	-0.38	5	5
NRIP1	-0.085	0.38	-10000	0	-1.2	53	53
RXRs/RARs	-0.011	0.15	-10000	0	-0.42	55	55
RXRs/RXRs/DNA/9cRA	0.003	0.12	-10000	0	-0.4	9	9
PRKACA	0.018	0	-10000	0	-10000	0	0
CDK7	0.017	0.012	-10000	0	-0.25	1	1
TFIIH	0.033	0.031	-10000	0	-0.3	4	4
RAR alpha/9cRA	0.04	0.041	-10000	0	-0.27	3	3
CCNH	0.014	0.047	-10000	0	-0.52	4	4
CREBBP	0.016	0.033	-10000	0	-0.52	2	2
RAR gamma2/9cRA	-0.002	0.022	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.002	0.14	-9999	-1.1	5	5
MKNK1	0.018	0	-9999	-10000	0	0
MAPK14	0.006	0.055	-9999	-0.29	6	6
ATF2/c-Jun	-0.028	0.19	-9999	-0.64	44	44
MAPK11	0.006	0.053	-9999	-0.28	5	5
MITF	0.014	0.071	-9999	-0.34	11	11
MAPKAPK5	0.018	0.059	-9999	-0.33	5	5
KRT8	-0.004	0.1	-9999	-0.34	31	31
MAPKAPK3	0.017	0.017	-9999	-0.25	2	2
MAPKAPK2	0.014	0.047	-9999	-0.52	4	4
p38alpha-beta/CK2	0.009	0.074	-9999	-0.37	7	7
CEBPB	0.011	0.072	-9999	-0.32	11	11
SLC9A1	0.018	0.059	-9999	-0.33	5	5
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.013	0.079	-9999	-0.31	6	6
p38alpha-beta/MNK1	0.023	0.059	-9999	-0.32	5	5
JUN	-0.028	0.19	-9999	-0.63	44	44
PPARGC1A	0.003	0.088	-9999	-0.35	15	15
USF1	0.006	0.084	-9999	-0.36	14	14
RAB5/GDP/GDI1	0.019	0.042	-9999	-0.22	6	6
NOS2	0.008	0.059	-9999	-0.3	7	7
DDIT3	0.014	0.066	-9999	-0.37	6	6
RAB5A	0.018	0	-9999	-10000	0	0
HSPB1	-0.012	0.12	-9999	-0.33	54	54
p38alpha-beta/HBP1	0.021	0.066	-9999	-0.34	8	8
CREB1	0.014	0.075	-9999	-0.28	17	17
RAB5/GDP	0.013	0	-9999	-10000	0	0
EIF4E	0.025	0.049	-9999	-0.27	5	5
RPS6KA4	0.018	0.061	-9999	-0.32	6	6
PLA2G4A	-0.006	0.1	-9999	-0.31	30	30
GDI1	0.017	0.061	-9999	-0.32	6	6
TP53	-0.001	0.096	-9999	-0.34	21	21
RPS6KA5	0	0.1	-9999	-0.34	33	33
ESR1	-0.09	0.17	-9999	-0.33	155	155
HBP1	0.015	0.04	-9999	-0.52	3	3
MEF2C	-0.001	0.1	-9999	-0.34	32	32
MEF2A	0.017	0.062	-9999	-0.33	6	6
EIF4EBP1	0.008	0.08	-9999	-0.29	18	18
KRT19	-0.014	0.12	-9999	-0.34	53	53
ELK4	0.016	0.065	-9999	-0.31	9	9
ATF6	0.018	0.06	-9999	-0.32	6	6
ATF1	0.014	0.076	-9999	-0.28	18	18
p38alpha-beta/MAPKAPK2	0.02	0.069	-9999	-0.37	8	8
p38alpha-beta/MAPKAPK3	0.022	0.059	-9999	-0.3	6	6

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.001	0.094	-9999	-0.4	22	22
AKT1	0.029	0.15	-9999	-0.49	23	23
PTK2B	0.015	0.13	-9999	-0.56	15	15
VEGFR2 homodimer/Frs2	0.02	0.098	-9999	-0.52	12	12
CAV1	-0.001	0.083	-9999	-0.33	29	29
CALM1	0.018	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.019	0.11	-9999	-0.55	11	11
endothelial cell proliferation	0.046	0.13	-9999	-0.46	18	18
mol:Ca2+	0.014	0.14	-9999	-0.57	17	17
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.033	0.1	-9999	-0.54	10	10
RP11-342D11.1	0.005	0.14	-9999	-0.58	16	16
CDH5	0.013	0.052	-9999	-0.52	5	5
VEGFA homodimer	0.003	0.099	-9999	-0.27	52	52
SHC1	0.017	0.023	-9999	-0.52	1	1
SHC2	-0.06	0.19	-9999	-0.51	77	77
HRAS/GDP	-0.036	0.099	-9999	-0.5	16	16
SH2D2A	-0.039	0.15	-9999	-0.38	76	76
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.044	0.12	-9999	-0.45	17	17
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.008	0.14	-9999	-0.54	15	15
VEGFR1 homodimer	0.004	0.08	-9999	-0.45	15	15
SHC/GRB2/SOS1	0.026	0.13	-9999	-0.55	16	16
GRB10	0.005	0.17	-9999	-0.61	28	28
PTPN11	0.017	0.023	-9999	-0.52	1	1
GRB2	0.016	0.024	-9999	-0.25	4	4
PAK1	-0.022	0.13	-9999	-0.37	54	54
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.029	0.12	-9999	-0.52	15	15
HRAS	0.012	0.051	-9999	-0.41	7	7
VEGF/Rho/ROCK1/Integrin Complex	0.018	0.12	-9999	-0.56	13	13
HIF1A	-0.037	0.16	-9999	-0.46	61	61
FRS2	0.011	0.047	-9999	-0.27	13	13
oxygen and reactive oxygen species metabolic process	0.031	0.1	-9999	-0.53	10	10
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.018	0	-9999	-10000	0	0
Nck/Pak	-0.007	0.095	-9999	-0.37	25	25
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.018	0.12	-9999	-0.63	11	11
mol:GDP	-0.038	0.1	-9999	-0.53	16	16
mol:NADP	0.042	0.11	-9999	-0.4	17	17
eNOS/Hsp90	0.047	0.11	-9999	-0.38	16	16
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
mol:IP3	0.014	0.14	-9999	-0.58	17	17
HIF1A/ARNT	-0.014	0.12	-9999	-0.37	47	47
SHB	0.008	0.067	-9999	-0.41	12	12
VEGFA	-0.002	0.076	-9999	-0.28	31	31
VEGFC	-0.001	0.095	-9999	-0.47	20	20
FAK1/Vinculin	0.034	0.13	-9999	-0.79	7	7
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.005	0.08	-9999	-0.52	12	12
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.015	0.14	-9999	-0.6	15	15
PTPN6	0.015	0.035	-9999	-0.43	3	3
EPAS1	0.012	0.088	-9999	-0.46	16	16
mol:L-citrulline	0.042	0.11	-9999	-0.4	17	17
ITGAV	-0.002	0.1	-9999	-0.48	21	21
PIK3CA	0.016	0.029	-9999	-0.34	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.028	0.11	-9999	-0.52	11	11
VEGFR2 homodimer/VEGFA homodimer	0.013	0.15	-9999	-0.64	16	16
VEGFR2/3 heterodimer	0.024	0.095	-9999	-0.56	10	10
VEGFB	0.017	0.023	-9999	-0.52	1	1
MAPK11	0.015	0.14	-9999	-0.56	19	19
VEGFR2 homodimer	0.018	0.11	-9999	-0.55	15	15
FLT1	0.004	0.08	-9999	-0.45	15	15
NEDD4	0.001	0.093	-9999	-0.53	15	15
MAPK3	0.017	0.13	-9999	-0.52	17	17
MAPK1	0.016	0.13	-9999	-0.52	17	17
VEGFA145/NRP2	0.009	0.065	-9999	-0.35	9	9
VEGFR1/2 heterodimer	0.016	0.11	-9999	-0.47	20	20
KDR	0.018	0.11	-9999	-0.55	15	15
VEGFA165/NRP1/VEGFR2 homodimer	0.017	0.14	-9999	-0.57	18	18
SRC	0.015	0.035	-9999	-0.43	3	3
platelet activating factor biosynthetic process	0.018	0.13	-9999	-0.54	17	17
PI3K	0.02	0.16	-9999	-0.57	23	23
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.02	0.11	-9999	-0.57	10	10
FES	0.011	0.15	-9999	-0.62	16	16
GAB1	0.02	0.15	-9999	-0.56	18	18
VEGFR2 homodimer/VEGFA homodimer/Src	0.022	0.11	-9999	-0.57	10	10
CTNNB1	0.001	0.09	-9999	-0.45	19	19
SOS1	0.017	0.023	-9999	-0.52	1	1
ARNT	0.018	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.041	0.12	-9999	-0.42	19	19
VEGFR2 homodimer/VEGFA homodimer/Yes	0.018	0.12	-9999	-0.54	13	13
PI3K/GAB1	0.027	0.16	-9999	-0.48	25	25
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.013	0.12	-9999	-0.44	18	18
PRKACA	0.018	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.024	0.12	-9999	-0.53	16	16
HSP90AA1	0.013	0.045	-9999	-0.39	6	6
CDC42	0.015	0.14	-9999	-0.6	16	16
actin cytoskeleton reorganization	-0.008	0.13	-9999	-0.53	15	15
PTK2	0.026	0.14	-9999	-0.66	12	12
EDG1	-0.003	0.19	-9999	-0.64	31	31
mol:DAG	0.014	0.14	-9999	-0.58	17	17
CaM/Ca2+	0.021	0.13	-9999	-0.53	17	17
MAP2K3	0.015	0.14	-9999	-0.55	19	19
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.011	0.18	-9999	-0.62	28	28
PLCG1	0.014	0.14	-9999	-0.59	17	17
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.027	0.11	-9999	-0.48	15	15
IQGAP1	0.018	0	-9999	-10000	0	0
YES1	0.007	0.07	-9999	-0.43	12	12
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.023	0.11	-9999	-0.57	11	11
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.022	0.11	-9999	-0.57	10	10
cell migration	0.055	0.12	-9999	-0.64	8	8
mol:PI-3-4-5-P3	0.021	0.15	-9999	-0.53	23	23
FYN	0.008	0.067	-9999	-0.41	12	12
VEGFB/NRP1	0.014	0.13	-9999	-0.56	16	16
mol:NO	0.042	0.11	-9999	-0.4	17	17
PXN	0.018	0	-9999	-10000	0	0
HRAS/GTP	-0.036	0.098	-9999	-0.5	16	16
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.009	0.17	-9999	-0.62	28	28
VHL	0.015	0.029	-9999	-0.25	6	6
ITGB3	0.002	0.075	-9999	-0.32	25	25
NOS3	0.041	0.12	-9999	-0.45	17	17
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.021	0.15	-9999	-0.48	25	25
RAC1	0.018	0	-9999	-10000	0	0
PRKCA	0.019	0.13	-9999	-0.5	20	20
PRKCB	0.012	0.13	-9999	-0.54	17	17
VCL	0.016	0.029	-9999	-0.34	3	3
VEGFA165/NRP1	0.008	0.14	-9999	-0.59	16	16
VEGFR1/2 heterodimer/VEGFA homodimer	0.016	0.12	-9999	-0.57	14	14
VEGFA165/NRP2	0.009	0.065	-9999	-0.35	9	9
MAPKKK cascade	0.031	0.15	-9999	-0.51	28	28
NRP2	0.011	0.052	-9999	-0.33	11	11
VEGFC homodimer	-0.001	0.095	-9999	-0.47	20	20
NCK1	0.011	0.045	-9999	-0.28	12	12
ROCK1	0.018	0	-9999	-10000	0	0
FAK1/Paxillin	0.035	0.13	-9999	-0.78	7	7
MAP3K13	0.01	0.15	-9999	-0.58	19	19
PDPK1	0.027	0.14	-9999	-0.47	23	23

×

Neurotrophic factor-mediated Trk receptor 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
CRKL	0.014	0.047	-10000	0	-0.52	4	4
RAS family/GTP/Tiam1	0.003	0.08	-10000	0	-0.28	28	28
NT3 (dimer)/TRKC	-0.019	0.093	-10000	0	-0.35	17	17
NT3 (dimer)/TRKB	-0.015	0.1	-10000	0	-0.32	37	37
SHC/Grb2/SOS1/GAB1/PI3K	0.023	0.065	-10000	0	-10000	0	0
RAPGEF1	0.018	0	-10000	0	-10000	0	0
BDNF	-0.016	0.091	-10000	0	-0.26	64	64
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
DYNLT1	0.018	0	-10000	0	-10000	0	0
NTRK1	0.01	0.053	-10000	0	-0.32	12	12
NTRK2	-0.017	0.11	-10000	0	-0.34	52	52
NTRK3	-0.009	0.081	-10000	0	-0.25	53	53
NT-4/5 (dimer)/TRKB	-0.004	0.079	-10000	0	-0.31	23	23
neuron apoptosis	0.036	0.15	0.34	79	-10000	0	79
SHC 2-3/Grb2	-0.039	0.16	-10000	0	-0.37	79	79
SHC1	0.017	0.023	-10000	0	-0.52	1	1
SHC2	-0.061	0.2	-10000	0	-0.5	78	78
SHC3	-0.007	0.11	-10000	0	-0.46	18	18
STAT3 (dimer)	-0.045	0.14	-10000	0	-0.34	89	89
NT3 (dimer)/TRKA	0.001	0.083	-10000	0	-0.33	17	17
RIN/GDP	0.047	0.05	-10000	0	-0.24	3	3
GIPC1	0.014	0.042	-10000	0	-0.45	4	4
KRAS	0.009	0.065	-10000	0	-0.44	10	10
DNAJA3	0.017	0.066	0.23	21	-0.26	6	27
RIN/GTP	0.011	0.025	-10000	0	-0.31	3	3
CCND1	-0.12	0.29	-10000	0	-0.75	89	89
MAGED1	-0.008	0.11	-10000	0	-0.48	27	27
PTPN11	0.017	0.023	-10000	0	-0.52	1	1
RICS	0.003	0.083	-10000	0	-0.45	16	16
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.034	0.025	-10000	0	-0.3	2	2
GRB2	0.016	0.024	-10000	0	-0.25	4	4
NGF (dimer)/TRKA/MATK	0.008	0.054	-10000	0	-0.3	7	7
TRKA/NEDD4-2	-0.01	0.11	-10000	0	-0.37	39	39
ELMO1	0.017	0.017	-10000	0	-0.25	2	2
RhoG/GTP/ELMO1/DOCK1	0.016	0.049	-10000	0	-0.31	11	11
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.012	0.051	-10000	0	-0.41	7	7
DOCK1	0.006	0.078	-10000	0	-0.5	12	12
GAB2	0.009	0.048	-10000	0	-0.25	17	17
RIT2	0.015	0.035	-10000	0	-0.43	3	3
RIT1	0.016	0.033	-10000	0	-0.52	2	2
FRS2	0.011	0.047	-10000	0	-0.27	13	13
DNM1	0.013	0.047	-10000	0	-0.37	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.016	0.033	-10000	0	-0.52	2	2
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.018	0.064	0.22	21	-0.25	6	27
mol:GDP	0.053	0.065	-10000	0	-0.4	2	2
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.012	0.011	-10000	0	-0.17	2	2
RIT1/GDP	0.048	0.049	-10000	0	-0.26	2	2
TIAM1	0.006	0.073	-10000	0	-0.44	13	13
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
BDNF (dimer)/TRKB	-0.007	0.09	-10000	0	-0.32	24	24
KIDINS220/CRKL/C3G	0.023	0.034	-10000	0	-0.37	4	4
SHC/RasGAP	0.016	0.059	-10000	0	-0.37	11	11
FRS2 family/SHP2	0.031	0.032	-10000	0	-0.3	2	2
SHC/GRB2/SOS1/GAB1	0.037	0.049	-10000	0	-0.26	12	12
RIT1/GTP	0.012	0.024	-10000	0	-0.38	2	2
NT3 (dimer)	-0.021	0.11	-10000	0	-0.28	68	68
RAP1/GDP	-0.006	0.028	-10000	0	-0.26	2	2
KIDINS220/CRKL	0.014	0.047	-10000	0	-0.52	4	4
BDNF (dimer)	-0.016	0.09	-10000	0	-0.26	64	64
ubiquitin-dependent protein catabolic process	-0.007	0.091	-10000	0	-0.31	39	39
Schwann cell development	-0.008	0.017	-10000	0	-10000	0	0
EHD4	0.013	0.052	-10000	0	-0.52	5	5
FRS2 family/GRB2/SOS1	0.04	0.037	-10000	0	-0.39	2	2
FRS2 family/SHP2/CRK family/C3G/GAB2	0.038	0.037	-10000	0	-0.23	6	6
RAP1B	0.013	0.044	-10000	0	-0.32	8	8
RAP1A	0.012	0.057	-10000	0	-0.52	6	6
CDC42/GTP	-0.043	0.077	-10000	0	-0.35	14	14
ABL1	0.018	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.024	0.023	-10000	0	-0.37	1	1
Rap1/GTP	0.032	0.072	-10000	0	-0.39	8	8
STAT3	-0.045	0.14	-10000	0	-0.34	89	89
axon guidance	-0.041	0.074	-10000	0	-0.34	14	14
MAPK3	0.013	0.05	-10000	0	-0.26	8	8
MAPK1	0.013	0.052	-10000	0	-0.27	9	9
CDC42/GDP	0.048	0.048	-10000	0	-0.26	2	2
NTF3	-0.021	0.11	-10000	0	-0.28	68	68
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.018	0.036	-10000	0	-0.31	4	4
PI3K	0.005	0.082	-10000	0	-0.37	21	21
FRS3	0.017	0.012	-10000	0	-0.25	1	1
FAIM	0.016	0.029	-10000	0	-0.34	3	3
GAB1	0.006	0.074	-10000	0	-0.43	14	14
RASGRF1	0.007	0.076	0.23	20	-0.26	12	32
SOS1	0.017	0.023	-10000	0	-0.52	1	1
MCF2L	-0.009	0.083	-10000	0	-0.3	21	21
RGS19	0.014	0.039	-10000	0	-0.36	5	5
CDC42	0.018	0	-10000	0	-10000	0	0
RAS family/GTP	0.047	0.07	-10000	0	-0.38	7	7
Rac1/GDP	0.048	0.048	-10000	0	-0.26	2	2
NGF (dimer)/TRKA/GRIT	0.011	0.06	-10000	0	-0.31	15	15
neuron projection morphogenesis	-0.013	0.13	-10000	0	-0.53	10	10
NGF (dimer)/TRKA/NEDD4-2	-0.007	0.091	-10000	0	-0.31	39	39
MAP2K1	0.034	0.045	-10000	0	-0.24	11	11
NGFR	0.004	0.065	-10000	0	-0.29	23	23
NGF (dimer)/TRKA/GIPC/GAIP	0.028	0.047	-10000	0	-0.27	10	10
RAS family/GTP/PI3K	0.011	0.077	-10000	0	-0.25	39	39
FRS2 family/SHP2/GRB2/SOS1	0.047	0.037	-10000	0	-0.38	2	2
NRAS	0.005	0.076	-10000	0	-0.4	16	16
GRB2/SOS1	0.024	0.023	-10000	0	-0.37	1	1
PRKCI	0.002	0.085	-10000	0	-0.43	18	18
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.018	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.018	0.052	-10000	0	-0.48	4	4
RASA1	0.004	0.078	-10000	0	-0.42	16	16
TRKA/c-Abl	0.021	0.038	-10000	0	-0.37	3	3
SQSTM1	0.012	0.053	-10000	0	-0.48	6	6
BDNF (dimer)/TRKB/GIPC	0.007	0.081	-10000	0	-0.28	22	22
NGF (dimer)/TRKA/p62/Atypical PKCs	0.017	0.059	-10000	0	-0.26	20	20
MATK	-0.003	0.075	-10000	0	-0.27	38	38
NEDD4L	-0.025	0.14	-10000	0	-0.45	48	48
RAS family/GDP	-0.01	0.033	-10000	0	-0.28	1	1
NGF (dimer)/TRKA	0.009	0.07	0.24	21	-0.19	25	46
Rac1/GTP	-0.02	0.052	-10000	0	-0.22	19	19
FRS2 family/SHP2/CRK family	0.045	0.043	-10000	0	-0.26	8	8

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.017	0.079	-9999	-0.37	18	18
CRKL	0.014	0.047	-9999	-0.52	4	4
Rac1/GDP	0.013	0	-9999	-10000	0	0
DOCK1	0.006	0.078	-9999	-0.5	12	12
ITGA4	-0.007	0.1	-9999	-0.39	32	32
alpha4/beta7 Integrin/MAdCAM1	0.023	0.079	-9999	-0.29	27	27
EPO	-0.023	0.097	-9999	-0.25	80	80
alpha4/beta7 Integrin	0.009	0.074	-9999	-0.37	16	16
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0.033	-9999	-0.52	2	2
alpha4/beta1 Integrin	0.006	0.084	-9999	-0.41	17	17
EPO/EPOR (dimer)	-0.003	0.069	-9999	-0.32	2	2
lamellipodium assembly	0.022	0.069	-9999	-0.35	6	6
PIK3CA	0.016	0.029	-9999	-0.34	3	3
PI3K	0.005	0.082	-9999	-0.37	21	21
ARF6	0.016	0.033	-9999	-0.52	2	2
JAK2	0.007	0.079	-9999	-0.39	10	10
PXN	0.018	0	-9999	-10000	0	0
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
MADCAM1	0.014	0.033	-9999	-0.25	8	8
cell adhesion	0.021	0.079	-9999	-0.29	27	27
CRKL/CBL	0.023	0.035	-9999	-0.37	4	4
ITGB1	0.014	0.044	-9999	-0.41	5	5
SRC	-0.001	0.11	-9999	-0.31	48	48
ITGB7	0.018	0	-9999	-10000	0	0
RAC1	0.018	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.005	0.12	-9999	-0.35	46	46
p130Cas/Crk/Dock1	0.018	0.1	-9999	-0.46	8	8
VCAM1	-0.022	0.13	-9999	-0.42	48	48
RHOA	0.005	0.08	-9999	-0.52	12	12
alpha4/beta1 Integrin/Paxillin/GIT1	0.028	0.07	-9999	-0.3	18	18
BCAR1	0.006	0.1	-9999	-0.29	42	42
EPOR	0.016	0.02	-9999	-0.25	3	3
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.017	0.012	-9999	-0.25	1	1
GIT1	0.014	0.035	-9999	-0.3	6	6
Rac1/GTP	0.022	0.071	-9999	-0.36	6	6

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	-0.009	0.14	-9999	-0.7	13	13
VEGFR1 homodimer/NRP1	-0.021	0.14	-9999	-0.39	56	56
mol:DAG	-0.004	0.14	-9999	-0.66	12	12
VEGFR1 homodimer/NRP1/VEGFR 121	-0.017	0.14	-9999	-0.64	14	14
CaM/Ca2+	0.006	0.13	-9999	-0.63	12	12
HIF1A	-0.035	0.17	-9999	-0.51	56	56
GAB1	0.006	0.074	-9999	-0.43	14	14
AKT1	-0.001	0.14	-9999	-0.57	17	17
PLCG1	-0.004	0.14	-9999	-0.67	12	12
NOS3	0.018	0.12	-9999	-0.56	13	13
CBL	0.017	0.012	-9999	-0.25	1	1
mol:NO	0.019	0.12	-9999	-0.53	13	13
FLT1	-0.021	0.16	-9999	-0.45	56	56
PGF	0.012	0.051	-9999	-0.41	7	7
VEGFR1 homodimer/NRP2/VEGFR121	-0.01	0.14	-9999	-0.64	15	15
CALM1	0.018	0	-9999	-10000	0	0
PIK3CA	0.016	0.029	-9999	-0.34	3	3
eNOS/Hsp90	0.026	0.12	-9999	-0.54	12	12
endothelial cell proliferation	0	0.13	-9999	-0.6	14	14
mol:Ca2+	-0.004	0.13	-9999	-0.66	12	12
MAPK3	0.007	0.12	-9999	-0.57	13	13
MAPK1	0.007	0.12	-9999	-0.58	12	12
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
PLGF homodimer	0.012	0.051	-9999	-0.41	7	7
PRKACA	0.018	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.001	0.083	-9999	-0.33	29	29
VEGFA homodimer	0	0.075	-9999	-0.29	31	31
VEGFR1 homodimer/VEGFA homodimer	-0.019	0.15	-9999	-0.68	14	14
platelet activating factor biosynthetic process	0.012	0.12	-9999	-0.57	12	12
PI3K	-0.004	0.15	-9999	-0.61	16	16
PRKCA	0.001	0.13	-9999	-0.61	12	12
PRKCB	-0.005	0.13	-9999	-0.62	12	12
VEGFR1 homodimer/PLGF homodimer	-0.012	0.15	-9999	-0.7	13	13
VEGFA	0	0.075	-9999	-0.29	31	31
VEGFB	0.017	0.023	-9999	-0.52	1	1
mol:IP3	-0.004	0.14	-9999	-0.66	12	12
RASA1	-0.008	0.14	-9999	-0.67	13	13
NRP2	0.011	0.052	-9999	-0.33	11	11
VEGFR1 homodimer	-0.021	0.16	-9999	-0.45	56	56
VEGFB homodimer	0.017	0.023	-9999	-0.52	1	1
NCK1	0.011	0.045	-9999	-0.28	12	12
eNOS/Caveolin-1	0.02	0.13	-9999	-0.57	14	14
PTPN11	0.017	0.023	-9999	-0.52	1	1
mol:PI-3-4-5-P3	-0.005	0.14	-9999	-0.6	16	16
mol:L-citrulline	0.019	0.12	-9999	-0.53	13	13
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.004	0.13	-9999	-0.62	13	13
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.009	0.14	-9999	-0.65	14	14
CD2AP	0.016	0.029	-9999	-0.34	3	3
PI3K/GAB1	-0.001	0.14	-9999	-0.56	17	17
PDPK1	-0.003	0.13	-9999	-0.56	16	16
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.007	0.14	-9999	-0.63	14	14
mol:NADP	0.019	0.12	-9999	-0.53	13	13
HSP90AA1	0.013	0.045	-9999	-0.39	6	6
ubiquitin-dependent protein catabolic process	0.003	0.13	-9999	-0.61	13	13
VEGFR1 homodimer/NRP2	-0.013	0.15	-9999	-0.69	14	14

×

LPA4-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.011	0.053	-9999	-0.31	13	13
ADCY5	-0.01	0.074	-9999	-0.32	15	15
ADCY6	0.014	0.042	-9999	-0.31	8	8
ADCY7	0.007	0.06	-9999	-0.32	14	14
ADCY1	0.015	0.038	-9999	-0.31	6	6
ADCY2	-0.03	0.11	-9999	-0.33	51	51
ADCY3	0.01	0.054	-9999	-0.31	13	13
ADCY8	0.011	0.046	-9999	-0.31	7	7
PRKCE	0.007	0.044	-9999	-0.31	9	9
ADCY9	0.002	0.075	-9999	-0.33	24	24
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.002	0.072	-9999	-0.28	18	18

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.014	0.044	-9999	-0.41	5	5
ITGB7	0.018	0	-9999	-10000	0	0
ITGA4	-0.007	0.1	-9999	-0.39	32	32
alpha4/beta7 Integrin	0.009	0.074	-9999	-0.37	16	16
alpha4/beta1 Integrin	0.006	0.084	-9999	-0.41	17	17

×

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

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
MET/RANBP9	0.014	0.053	-10000	0	-0.37	4	4
CRKL	0.02	0.086	-10000	0	-0.44	12	12
mol:PIP3	-0.004	0.091	0.46	19	-10000	0	19
AKT1	0.007	0.068	0.34	18	-0.28	4	22
PTK2B	0.017	0.017	-10000	0	-0.25	2	2
RAPGEF1	0.026	0.082	-10000	0	-0.42	11	11
RANBP10	0.018	0	-10000	0	-10000	0	0
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
HGF/MET/SHIP2	0.016	0.071	-10000	0	-0.31	18	18
MAP3K5	0.018	0.099	-10000	0	-0.41	14	14
HGF/MET/CIN85/CBL/ENDOPHILINS	0.021	0.079	-10000	0	-0.29	24	24
AP1	-0.087	0.16	-10000	0	-0.37	110	110
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.017	0.023	-10000	0	-0.52	1	1
apoptosis	-0.14	0.3	-10000	0	-0.74	100	100
STAT3 (dimer)	0.029	0.058	-10000	0	-0.29	2	2
GAB1/CRKL/SHP2/PI3K	0.029	0.098	-10000	0	-0.4	15	15
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.03	0.081	-10000	0	-0.44	10	10
PTPN11	0.017	0.023	-10000	0	-0.52	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.016	0.026	-10000	0	-0.39	2	2
PTEN	-0.002	0.1	-10000	0	-0.52	19	19
ELK1	-0.005	0.036	0.25	3	-0.18	5	8
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.023	0.045	-10000	0	-0.23	7	7
PAK1	-0.005	0.089	0.32	17	-0.26	29	46
HGF/MET/RANBP10	0.02	0.063	-10000	0	-0.31	13	13
HRAS	0.025	0.077	-10000	0	-0.52	6	6
DOCK1	0.021	0.093	-10000	0	-0.47	11	11
GAB1	0.016	0.087	-10000	0	-0.43	14	14
CRK	0.021	0.084	-10000	0	-0.45	11	11
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.021	0.083	-10000	0	-0.49	12	12
JUN	-0.034	0.15	-10000	0	-0.46	57	57
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.005	0.05	-10000	0	-0.24	17	17
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
cell morphogenesis	0.039	0.088	-10000	0	-0.36	9	9
GRB2/SHC	0.024	0.049	-10000	0	-0.23	11	11
FOS	-0.11	0.2	-10000	0	-0.37	171	171
GLMN	-0.001	0.014	-10000	0	-0.25	1	1
cell motility	-0.005	0.036	0.25	3	-0.18	5	8
HGF/MET/MUC20	0.008	0.062	-10000	0	-0.32	13	13
cell migration	0.024	0.048	-10000	0	-0.23	11	11
GRB2	0.016	0.024	-10000	0	-0.25	4	4
CBL	0.017	0.012	-10000	0	-0.25	1	1
MET/RANBP10	0.014	0.053	-10000	0	-0.37	4	4
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.025	0.059	-10000	0	-0.3	2	2
MET/MUC20	0.001	0.052	-10000	0	-0.2	31	31
RAP1B	0.03	0.08	-10000	0	-0.39	12	12
RAP1A	0.03	0.087	-10000	0	-0.44	12	12
HGF/MET/RANBP9	0.019	0.063	-10000	0	-0.31	13	13
RAF1	0.031	0.073	-10000	0	-0.48	6	6
STAT3	0.029	0.059	-10000	0	-0.29	2	2
cell proliferation	0.037	0.07	-10000	0	-0.32	13	13
RPS6KB1	0.009	0.023	-10000	0	-0.15	1	1
MAPK3	-0.01	0.04	0.66	1	-10000	0	1
MAPK1	-0.009	0.055	0.76	2	-10000	0	2
RANBP9	0.017	0.012	-10000	0	-0.25	1	1
MAPK8	0.025	0.093	-10000	0	-0.4	8	8
SRC	0.029	0.058	-10000	0	-0.28	2	2
PI3K	0.011	0.077	-10000	0	-0.26	29	29
MET/Glomulin	0.005	0.047	-10000	0	-0.3	5	5
SOS1	0.017	0.023	-10000	0	-0.52	1	1
MAP2K1	0.037	0.069	-10000	0	-0.44	6	6
MET	0	0.075	-10000	0	-0.29	31	31
MAP4K1	0.03	0.081	-10000	0	-0.46	9	9
PTK2	0.016	0.029	-10000	0	-0.34	3	3
MAP2K2	0.036	0.073	-10000	0	-0.47	6	6
BAD	0.013	0.064	0.32	18	-0.26	5	23
MAP2K4	0.015	0.1	-10000	0	-0.35	17	17
SHP2/GRB2/SOS1/GAB1	-0.016	0.067	-10000	0	-0.38	13	13
INPPL1	0.012	0.055	-10000	0	-0.44	7	7
PXN	0.018	0	-10000	0	-10000	0	0
SH3KBP1	0	0.086	-10000	0	-0.38	23	23
HGS	0.012	0.048	-10000	0	-0.22	18	18
PLCgamma1/PKC	0.012	0.019	-10000	0	-0.27	2	2
HGF	0.008	0.069	-10000	0	-0.45	11	11
RASA1	0.004	0.078	-10000	0	-0.42	16	16
NCK1	0.011	0.045	-10000	0	-0.28	12	12
PTPRJ	0.012	0.055	-10000	0	-0.44	7	7
NCK/PLCgamma1	0.024	0.055	-10000	0	-0.24	12	12
PDPK1	0.003	0.07	0.37	18	-10000	0	18
HGF/MET/SHIP	0.008	0.062	-10000	0	-0.32	13	13

×

EPO signaling pathway

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
BCL2L1	-0.029	0.17	-10000	0	-0.44	13	13
CRKL	0.006	0.074	-10000	0	-0.3	8	8
mol:DAG	0.006	0.083	-10000	0	-0.27	5	5
HRAS	0.024	0.075	-10000	0	-0.41	2	2
MAPK8	0.009	0.058	-10000	0	-0.28	4	4
RAP1A	0.005	0.077	-10000	0	-0.32	9	9
GAB1	0.002	0.08	-10000	0	-0.28	13	13
MAPK14	0.011	0.054	-10000	0	-0.22	2	2
EPO	-0.025	0.098	-10000	0	-0.26	80	80
PLCG1	0.006	0.084	-10000	0	-0.28	5	5
EPOR/TRPC2/IP3 Receptors	0.013	0.024	-10000	0	-0.27	3	3
RAPGEF1	0.018	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.001	0.073	-10000	0	-0.32	10	10
GAB1/SHC/GRB2/SOS1	0.02	0.074	-10000	0	-0.43	2	2
EPO/EPOR (dimer)	-0.005	0.071	-10000	0	-0.28	3	3
IRS2	-0.013	0.1	-10000	0	-0.31	34	34
STAT1	-0.026	0.14	-10000	0	-0.32	61	61
STAT5B	-0.002	0.1	-10000	0	-0.28	8	8
cell proliferation	0.016	0.054	-10000	0	-0.27	3	3
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.031	0.066	-10000	0	-0.31	12	12
TEC	0.005	0.074	-10000	0	-0.28	9	9
SOCS3	0.005	0.074	-10000	0	-0.38	17	17
STAT1 (dimer)	-0.026	0.14	-10000	0	-0.31	61	61
JAK2	0.008	0.054	-10000	0	-0.32	12	12
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
EPO/EPOR (dimer)/JAK2	0.015	0.083	-10000	0	-0.29	6	6
EPO/EPOR	-0.005	0.071	-10000	0	-0.28	3	3
LYN	0.012	0.033	-10000	0	-0.26	7	7
TEC/VAV2	0.014	0.076	-10000	0	-0.29	6	6
elevation of cytosolic calcium ion concentration	0.013	0.023	-10000	0	-0.27	3	3
SHC1	0.017	0.023	-10000	0	-0.52	1	1
EPO/EPOR (dimer)/LYN	0.009	0.066	-10000	0	-0.26	2	2
mol:IP3	0.006	0.083	-10000	0	-0.27	5	5
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.017	0.11	-10000	0	-0.32	39	39
SH2B3	0.015	0.024	-10000	0	-0.52	1	1
NFKB1	0.01	0.055	-10000	0	-0.27	2	2
EPO/EPOR (dimer)/JAK2/SOCS3	-0.004	0.05	0.26	1	-0.23	11	12
PTPN6	0	0.072	-10000	0	-0.29	6	6
TEC/VAV2/GRB2	0.021	0.074	-10000	0	-0.33	3	3
EPOR	0.013	0.024	-10000	0	-0.27	3	3
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.075	-10000	0	-0.44	2	2
SOS1	0.017	0.023	-10000	0	-0.52	1	1
PLCG2	-0.017	0.11	-10000	0	-0.32	55	55
CRKL/CBL/C3G	0.023	0.073	-10000	0	-0.36	3	3
VAV2	0.007	0.071	-10000	0	-0.3	4	4
CBL	0.008	0.07	-10000	0	-0.3	4	4
SHC/Grb2/SOS1	-0.021	0.044	-10000	0	-0.27	5	5
STAT5A	-0.005	0.11	-10000	0	-0.31	9	9
GRB2	0.016	0.024	-10000	0	-0.25	4	4
STAT5 (dimer)	-0.013	0.15	-10000	0	-0.35	40	40
LYN/PLCgamma2	-0.002	0.082	-10000	0	-0.36	16	16
PTPN11	0.017	0.023	-10000	0	-0.52	1	1
BTK	-0.005	0.092	-10000	0	-0.31	23	23
BCL2	-0.15	0.38	-10000	0	-0.86	117	117

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.018	0	-10000	0	-10000	0	0
NFATC1	0.033	0.073	-10000	0	-10000	0	0
NFATC2	0.027	0.041	-10000	0	-0.25	1	1
NFATC3	0.017	0.006	-10000	0	-10000	0	0
YWHAE	0.016	0.029	-10000	0	-0.34	3	3
Calcineurin A alpha-beta B1/CABIN1	0.003	0.094	-10000	0	-0.37	14	14
Exportin 1/Ran/NUP214	0.035	0.018	-10000	0	-0.3	1	1
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.021	0.09	-10000	0	-0.42	9	9
BCL2/BAX	-0.071	0.16	-10000	0	-0.37	115	115
CaM/Ca2+/Calcineurin A alpha-beta B1	0.015	0.003	-10000	0	-10000	0	0
CaM/Ca2+	0.015	0.003	-10000	0	-10000	0	0
BAX	0.016	0.02	-10000	0	-0.25	3	3
MAPK14	0.018	0.012	-10000	0	-0.25	1	1
BAD	0.017	0.023	-10000	0	-0.52	1	1
CABIN1/MEF2D	0.012	0.09	-10000	0	-0.39	11	11
Calcineurin A alpha-beta B1/BCL2	-0.11	0.22	-10000	0	-0.47	144	144
FKBP8	0.017	0.012	-10000	0	-0.25	1	1
activation-induced cell death of T cells	-0.012	0.089	0.38	11	-10000	0	11
KPNB1	0.012	0.057	-10000	0	-0.52	6	6
KPNA2	-0.001	0.084	-10000	0	-0.34	27	27
XPO1	0.018	0	-10000	0	-10000	0	0
SFN	-0.015	0.12	-10000	0	-0.45	37	37
MAP3K8	-0.036	0.15	-10000	0	-0.39	70	70
NFAT4/CK1 alpha	0.011	0.074	-10000	0	-0.24	37	37
MEF2D/NFAT1/Cbp/p300	0.057	0.059	-10000	0	-0.33	3	3
CABIN1	0.003	0.095	-10000	0	-0.38	14	14
CALM1	0.018	0.001	-10000	0	-10000	0	0
RAN	0.017	0.012	-10000	0	-0.25	1	1
MAP3K1	-0.03	0.14	-10000	0	-0.42	58	58
CAMK4	0.011	0.052	-10000	0	-0.33	11	11
mol:Ca2+	0.001	0.002	-10000	0	-10000	0	0
MAPK3	0.016	0.026	-10000	0	-0.39	2	2
YWHAH	0.013	0.048	-10000	0	-0.47	5	5
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.01	0.11	-10000	0	-0.37	39	39
YWHAB	0.015	0.037	-10000	0	-0.39	4	4
MAPK8	0.015	0.041	-10000	0	-0.52	3	3
MAPK9	-0.006	0.11	-10000	0	-0.51	24	24
YWHAG	0.017	0.017	-10000	0	-0.25	2	2
FKBP1A	0.017	0.017	-10000	0	-0.25	2	2
NFAT1-c-4/YWHAQ	0.051	0.067	-10000	0	-0.28	1	1
PRKCH	0.011	0.056	-10000	0	-0.42	8	8
CABIN1/Cbp/p300	0.023	0.042	-10000	0	-0.37	6	6
CASP3	0.018	0.001	-10000	0	-10000	0	0
PIM1	0.013	0.035	-10000	0	-0.25	9	9
Calcineurin A alpha-beta B1/FKBP12/FK506	0.012	0.009	-10000	0	-10000	0	0
apoptosis	-0.026	0.046	-10000	0	-0.32	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.033	0.052	-10000	0	-0.33	1	1
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.01	0.06	-10000	0	-0.43	9	9
JNK2/NFAT4	0.013	0.062	-10000	0	-0.28	23	23
BAD/BCL-XL	0.026	0.017	-10000	0	-0.37	1	1
PRKCD	0.014	0.042	-10000	0	-0.45	4	4
NUP214	0.016	0.026	-10000	0	-0.39	2	2
PRKCZ	0	0.001	-10000	0	-10000	0	0
PRKCA	0.014	0.033	-10000	0	-0.25	8	8
PRKCG	0.018	0	-10000	0	-10000	0	0
PRKCQ	-0.014	0.1	-10000	0	-0.31	51	51
FKBP38/BCL2	-0.07	0.16	-10000	0	-0.37	115	115
EP300	0.014	0.047	-10000	0	-0.52	4	4
PRKCB1	-0.052	0.16	-10000	0	-0.39	90	90
CSNK2A1	0.017	0.023	-10000	0	-0.52	1	1
NFATc/JNK1	0.041	0.073	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0.025	0.007	-10000	0	-10000	0	0
FKBP12/FK506	0.012	0.011	-10000	0	-0.17	2	2
CSNK1A1	0.022	0.015	-10000	0	-0.31	1	1
CaM/Ca2+/CAMK IV	0.021	0.032	-10000	0	-0.31	3	3
NFATc/ERK1	0.041	0.073	-10000	0	-0.49	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.019	0.091	-10000	0	-0.42	10	10
NR4A1	0.052	0.066	-10000	0	-0.51	2	2
GSK3B	0.018	0.001	-10000	0	-10000	0	0
positive T cell selection	0.017	0.006	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.027	0.036	-10000	0	-0.25	2	2
RCH1/ KPNB1	0.009	0.074	-10000	0	-0.38	15	15
YWHAQ	0.014	0.039	-10000	0	-0.36	5	5
PRKACA	0.018	0.001	-10000	0	-10000	0	0
AKAP5	-0.033	0.15	-10000	0	-0.42	61	61
MEF2D	0.018	0.001	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.017	0.017	-10000	0	-0.25	2	2
NFATc/p38 alpha	0.042	0.07	-10000	0	-10000	0	0
CREBBP	0.016	0.033	-10000	0	-0.52	2	2
BCL2	-0.11	0.22	-10000	0	-0.47	144	144

×

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	0.041	0.037	-10000	0	-0.27	7	7
HDAC3	0.018	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.011	-10000	0	-0.22	1	1
GATA1/HDAC4	0.026	0.017	-10000	0	-0.37	1	1
GATA1/HDAC5	0.026	0.017	-10000	0	-0.37	1	1
GATA2/HDAC5	0.008	0.068	-10000	0	-0.37	10	10
HDAC5/BCL6/BCoR	0.016	0.078	-10000	0	-0.3	28	28
HDAC9	0.011	0.045	-10000	0	-0.28	12	12
Glucocorticoid receptor/Hsp90/HDAC6	0.021	0.068	-10000	0	-0.3	21	21
HDAC4/ANKRA2	0.013	0.072	-10000	0	-0.37	18	18
HDAC5/YWHAB	0.023	0.032	-10000	0	-0.37	3	3
NPC/RanGAP1/SUMO1/Ubc9	0.023	0.013	-10000	0	-0.2	1	1
GATA2	-0.007	0.093	-10000	0	-0.31	40	40
HDAC4/RFXANK	0.025	0.019	-10000	0	-0.37	1	1
BCOR	0.009	0.07	-10000	0	-0.52	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.015	0.037	-10000	0	-0.39	4	4
HDAC5	0.017	0.023	-10000	0	-0.52	1	1
GNB1/GNG2	0.021	0.043	-10000	0	-0.37	6	6
Histones	0.02	0.07	-10000	0	-0.25	29	29
ADRBK1	0.018	0	-10000	0	-10000	0	0
HDAC4	0.017	0.023	-10000	0	-0.52	1	1
XPO1	0.018	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.013	0.072	-10000	0	-0.37	18	18
HDAC4/Ubc9	0.026	0.017	-10000	0	-0.37	1	1
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.024	0.027	-10000	0	-0.37	2	2
TUBA1B	0.018	0	-10000	0	-10000	0	0
HDAC6	0.018	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.025	0.019	-10000	0	-0.37	1	1
CAMK4	0.011	0.052	-10000	0	-0.33	11	11
Tubulin/HDAC6	0.022	0.063	-10000	0	-0.3	17	17
SUMO1	0.018	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.015	0.037	-10000	0	-0.39	4	4
GATA1	0.018	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.016	0.029	-10000	0	-0.34	3	3
NR3C1	-0.001	0.098	-10000	0	-0.51	19	19
SUMO1/HDAC4	0.036	0.019	-10000	0	-0.31	1	1
SRF	0.016	0.024	-10000	0	-0.25	4	4
HDAC4/YWHAB	0.023	0.032	-10000	0	-0.37	3	3
Tubulin	0.011	0.073	-10000	0	-0.37	17	17
HDAC4/14-3-3 E	0.024	0.03	-10000	0	-0.44	2	2
GNB1	0.013	0.052	-10000	0	-0.52	5	5
RANGAP1	0.014	0.037	-10000	0	-0.29	7	7
BCL6/BCoR	0.004	0.089	-10000	0	-0.37	27	27
HDAC4/HDAC3/SMRT (N-CoR2)	0.035	0.015	-10000	0	-0.3	1	1
HDAC4/SRF	0.03	0.037	-10000	0	-0.3	4	4
HDAC4/ER alpha	-0.1	0.18	-10000	0	-0.37	151	151
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.02	0.069	-10000	0	-0.25	29	29
cell motility	0.022	0.063	-10000	0	-0.3	17	17
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.018	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.013	0	-10000	0	-10000	0	0
BCL6	-0.004	0.1	-10000	0	-0.45	24	24
HDAC4/CaMK II delta B	0.017	0.023	-10000	0	-0.52	1	1
Hsp90/HDAC6	0.023	0.033	-10000	0	-0.37	3	3
ESR1	-0.16	0.24	-10000	0	-0.46	199	199
HDAC6/HDAC11	0.004	0.089	-10000	0	-0.37	28	28
Ran/GTP/Exportin 1	0.039	0.013	-10000	0	-10000	0	0
NPC	0.01	0.008	-10000	0	-10000	0	0
MEF2C	-0.014	0.12	-10000	0	-0.45	36	36
RAN	0.017	0.012	-10000	0	-0.25	1	1
HDAC4/MEF2C	0.035	0.069	-10000	0	-0.24	28	28
GNG2	0.016	0.029	-10000	0	-0.34	3	3
NCOR2	0.018	0	-10000	0	-10000	0	0
TUBB2A	-0.004	0.1	-10000	0	-0.43	26	26
HDAC11	-0.012	0.12	-10000	0	-0.5	31	31
HSP90AA1	0.013	0.045	-10000	0	-0.39	6	6
RANBP2	0.017	0.017	-10000	0	-0.25	2	2
ANKRA2	0	0.095	-10000	0	-0.52	17	17
RFXANK	0.017	0.012	-10000	0	-0.25	1	1
nuclear import	-0.032	0.035	0.31	5	-10000	0	5

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.014	0.047	-10000	0	-0.52	4	4
Rac1/GDP	0.003	0.012	-10000	0	-10000	0	0
DOCK1	0.006	0.078	-10000	0	-0.5	12	12
ITGA4	-0.007	0.1	-10000	0	-0.39	32	32
RAC1	0.018	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.009	0.074	-10000	0	-0.37	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.016	0.033	-10000	0	-0.52	2	2
alpha4/beta1 Integrin	0.019	0.073	-10000	0	-0.34	17	17
alpha4/beta7 Integrin/Paxillin	0.028	0.058	-10000	0	-0.27	16	16
lamellipodium assembly	0.028	0.091	-10000	0	-0.35	22	22
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
PI3K	0.005	0.082	-10000	0	-0.37	21	21
ARF6	0.016	0.033	-10000	0	-0.52	2	2
TLN1	0.017	0.023	-10000	0	-0.52	1	1
PXN	0.025	0	-10000	0	-10000	0	0
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
ARF6/GTP	0.031	0.061	-10000	0	-0.47	2	2
cell adhesion	0.033	0.064	-10000	0	-0.27	18	18
CRKL/CBL	0.023	0.035	-10000	0	-0.37	4	4
alpha4/beta1 Integrin/Paxillin	0.026	0.067	-10000	0	-0.3	17	17
ITGB1	0.014	0.044	-10000	0	-0.41	5	5
ITGB7	0.018	0	-10000	0	-10000	0	0
ARF6/GDP	0.001	0.034	-10000	0	-0.51	2	2
alpha4/beta1 Integrin/Paxillin/VCAM1	0.015	0.1	-10000	0	-0.3	40	40
p130Cas/Crk/Dock1	0.027	0.054	-10000	0	-0.3	13	13
VCAM1	-0.022	0.13	-10000	0	-0.42	48	48
alpha4/beta1 Integrin/Paxillin/Talin	0.035	0.065	-10000	0	-0.28	18	18
alpha4/beta1 Integrin/Paxillin/GIT1	0.034	0.066	-10000	0	-0.28	18	18
BCAR1	0.017	0.012	-10000	0	-0.25	1	1
mol:GDP	-0.032	0.065	0.27	18	-10000	0	18
CBL	0.017	0.012	-10000	0	-0.25	1	1
PRKACA	0.018	0	-10000	0	-10000	0	0
GIT1	0.014	0.035	-10000	0	-0.3	6	6
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.035	0.065	-10000	0	-0.28	18	18
Rac1/GTP	-0.019	0.087	-10000	0	-0.38	22	22

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	-0.009	0.07	0.39	11	-10000	0	11
KIRREL	0.007	0.075	-10000	0	-0.53	10	10
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.01	0.07	-10000	0	-0.39	11	11
PLCG1	0.016	0.026	-10000	0	-0.39	2	2
ARRB2	0.018	0	-10000	0	-10000	0	0
WASL	0.01	0.066	-10000	0	-0.52	8	8
Nephrin/NEPH1/podocin/CD2AP	0.028	0.059	-10000	0	-0.27	14	14
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.025	0.06	-10000	0	-0.25	14	14
FYN	0.014	0.059	-10000	0	-0.25	20	20
mol:Ca2+	0.027	0.06	-10000	0	-0.29	13	13
mol:DAG	0.028	0.06	-10000	0	-0.29	13	13
NPHS2	0.015	0.036	-10000	0	-0.43	3	3
mol:IP3	0.028	0.06	-10000	0	-0.29	13	13
regulation of endocytosis	0.028	0.058	-10000	0	-0.25	13	13
Nephrin/NEPH1/podocin/Cholesterol	0.018	0.056	-10000	0	-0.28	13	13
establishment of cell polarity	0.009	0.07	-10000	0	-0.39	11	11
Nephrin/NEPH1/podocin/NCK1-2	0.035	0.06	-10000	0	-0.25	14	14
Nephrin/NEPH1/beta Arrestin2	0.029	0.059	-10000	0	-0.26	13	13
NPHS1	0.004	0.061	-10000	0	-0.26	25	25
Nephrin/NEPH1/podocin	0.02	0.061	-10000	0	-0.25	20	20
TJP1	0.013	0.052	-10000	0	-0.52	5	5
NCK1	0.011	0.045	-10000	0	-0.28	12	12
NCK2	0.015	0.026	-10000	0	-0.25	5	5
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.029	0.061	-10000	0	-0.3	13	13
CD2AP	0.016	0.029	-10000	0	-0.34	3	3
Nephrin/NEPH1/podocin/GRB2	0.028	0.058	-10000	0	-0.27	13	13
GRB2	0.016	0.024	-10000	0	-0.25	4	4
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	0.012	0.068	-10000	0	-0.27	24	24
cytoskeleton organization	0.029	0.063	-10000	0	-0.27	14	14
Nephrin/NEPH1	0.011	0.049	-10000	0	-0.27	11	11
Nephrin/NEPH1/ZO-1	0.019	0.066	-10000	0	-0.31	16	16

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.002	0.081	-9999	-0.36	22	22
Aurora C/Aurora B/INCENP	0.016	0.061	-9999	-0.28	14	14
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.007	0.037	-9999	-0.52	2	2
AURKB	0.009	0.056	-9999	-0.31	14	14
AURKC	0.008	0.053	-9999	-0.27	18	18

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.04	0.082	-9999	-1.3	1	1
PLK1	0.03	0.18	-9999	-0.68	9	9
CDKN1B	0.062	0.17	-9999	-0.48	31	31
FOXO3	0.022	0.19	-9999	-0.57	21	21
KAT2B	0.003	0.02	-9999	-0.048	24	24
FOXO1/SIRT1	0.035	0.067	-9999	-0.37	5	5
CAT	0.024	0.2	-9999	-0.86	12	12
CTNNB1	0.001	0.09	-9999	-0.45	19	19
AKT1	0.019	0.057	-9999	-0.36	9	9
FOXO1	0.035	0.067	-9999	-0.33	7	7
MAPK10	0.014	0.073	-9999	-0.26	27	27
mol:GTP	0.001	0.003	-9999	-10000	0	0
FOXO4	0.061	0.1	-9999	-0.4	5	5
response to oxidative stress	0.008	0.022	-9999	-0.049	23	23
FOXO3A/SIRT1	0.035	0.16	-9999	-0.49	19	19
XPO1	0.018	0.001	-9999	-10000	0	0
EP300	0.017	0.047	-9999	-0.52	4	4
BCL2L11	0.027	0.038	-9999	-10000	0	0
FOXO1/SKP2	0.035	0.071	-9999	-0.42	5	5
mol:GDP	0.008	0.022	-9999	-0.049	23	23
RAN	0.018	0.012	-9999	-0.25	1	1
GADD45A	0.038	0.22	-9999	-0.9	21	21
YWHAQ	0.014	0.039	-9999	-0.36	5	5
FOXO1/14-3-3 family	0.066	0.061	-9999	-0.34	2	2
MST1	0.02	0.03	-9999	-0.29	3	3
CSNK1D	0.018	0	-9999	-10000	0	0
CSNK1E	0.017	0.012	-9999	-0.25	1	1
FOXO4/14-3-3 family	0.04	0.081	-9999	-0.56	1	1
YWHAB	0.015	0.037	-9999	-0.39	4	4
MAPK8	0.034	0.038	-9999	-0.26	7	7
MAPK9	0.023	0.067	-9999	-0.25	27	27
YWHAG	0.017	0.017	-9999	-0.25	2	2
YWHAE	0.016	0.029	-9999	-0.34	3	3
YWHAZ	0.017	0.017	-9999	-0.25	2	2
SIRT1	0.018	0.035	-9999	-0.35	3	3
SOD2	0.066	0.17	-9999	-0.58	12	12
RBL2	0.046	0.16	-9999	-0.82	6	6
RAL/GDP	0.031	0.034	-9999	-0.31	4	4
CHUK	0.009	0.083	-9999	-0.5	13	13
Ran/GTP	0.016	0.009	-9999	-0.16	1	1
CSNK1G2	0.016	0.033	-9999	-0.52	2	2
RAL/GTP	0.036	0.035	-9999	-0.28	4	4
CSNK1G1	0.017	0.012	-9999	-0.25	1	1
FASLG	-0.12	0.41	-9999	-1.4	49	49
SKP2	0.007	0.052	-9999	-0.25	20	20
USP7	0.018	0.012	-9999	-0.26	1	1
IKBKB	0.015	0.051	-9999	-0.31	10	10
CCNB1	-0.02	0.32	-9999	-1.1	37	37
FOXO1-3a-4/beta catenin	0.068	0.17	-9999	-0.41	24	24
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.071	-9999	-0.41	5	5
CSNK1A1	0.017	0.023	-9999	-0.52	1	1
SGK1	0.003	0.02	-9999	-0.048	24	24
CSNK1G3	0.013	0.052	-9999	-0.52	5	5
Ran/GTP/Exportin 1	0.028	0.011	-9999	-10000	0	0
ZFAND5	0.067	0.09	-9999	-0.39	1	1
SFN	-0.015	0.12	-9999	-0.45	37	37
CDK2	0.015	0.047	-9999	-0.3	10	10
FOXO3A/14-3-3	0.043	0.08	-9999	-0.35	7	7
CREBBP	0.019	0.033	-9999	-0.52	2	2
FBXO32	-0.007	0.3	-9999	-1.2	25	25
BCL6	0.016	0.26	-9999	-1.2	19	19
RALB	0.015	0.047	-9999	-0.52	4	4
RALA	0.019	0.002	-9999	-10000	0	0
YWHAH	0.013	0.048	-9999	-0.47	5	5

×

Circadian rhythm 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
chromatin modification	0.017	0.1	-10000	0	-1.3	1	1
CLOCK	0.02	0.024	-10000	0	-0.52	1	1
TIMELESS/CRY2	0.041	0.06	-10000	0	-1.2	1	1
DEC1/BMAL1	0.015	0.072	-10000	0	-0.39	15	15
ATR	0.017	0.012	-10000	0	-0.25	1	1
NR1D1	0.036	0.045	-10000	0	-10000	0	0
ARNTL	0.009	0.078	-10000	0	-0.49	12	12
TIMELESS	0.036	0.065	-10000	0	-1.3	1	1
NPAS2	-0.004	0.094	-10000	0	-0.32	39	39
CRY2	0.017	0.012	-10000	0	-0.25	1	1
mol:CO	-0.014	0.012	0.14	1	-10000	0	1
CHEK1	-0.046	0.16	-10000	0	-0.38	84	84
mol:HEME	0.014	0.012	-10000	0	-0.14	1	1
PER1	0.014	0.037	-10000	0	-0.29	7	7
BMAL/CLOCK/NPAS2	0.03	0.082	-10000	0	-0.32	21	21
BMAL1/CLOCK	0.042	0.076	-10000	0	-0.5	3	3
S phase of mitotic cell cycle	0.017	0.1	-10000	0	-1.3	1	1
TIMELESS/CHEK1/ATR	0.017	0.1	-10000	0	-1.4	1	1
mol:NADPH	0.014	0.012	-10000	0	-0.14	1	1
PER1/TIMELESS	0.039	0.063	-10000	0	-1.2	1	1
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.011	0.057	-10000	0	-0.4	9	9

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.01	0.078	0.29	16	-10000	0	16
GNAI2	0.006	0.075	-10000	0	-0.48	12	12
S1P/S1P5/G12	0.012	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.016	0.024	-10000	0	-0.25	4	4
RhoA/GTP	0.01	0.08	-10000	0	-0.29	16	16
negative regulation of cAMP metabolic process	0.008	0.072	-10000	0	-0.29	12	12
GNAZ	0.001	0.088	-10000	0	-0.44	19	19
GNAI3	0.018	0	-10000	0	-10000	0	0
GNA12	0.018	0	-10000	0	-10000	0	0
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.008	0.072	-10000	0	-0.29	12	12
RhoA/GDP	0.004	0.058	-10000	0	-0.38	12	12
RHOA	0.005	0.08	-10000	0	-0.52	12	12
GNAI1	-0.017	0.12	-10000	0	-0.38	46	46

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.015	0.065	-9999	-0.37	14	14
FBXW11	0.015	0.035	-9999	-0.43	3	3
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.015	0.035	-9999	-0.43	3	3
CHUK	0.005	0.081	-9999	-0.5	13	13
NF kappa B2 p100/RelB	0.034	0.074	-9999	-0.28	24	24
NFKB1	0.017	0.023	-9999	-0.52	1	1
MAP3K14	0.015	0.037	-9999	-0.39	4	4
NF kappa B1 p50/RelB	0.015	0.059	-9999	-0.37	10	10
RELB	0.003	0.078	-9999	-0.38	19	19
NFKB2	0.015	0.031	-9999	-0.32	4	4
NF kappa B2 p52/RelB	0.014	0.052	-9999	-0.31	11	11
regulation of B cell activation	0.014	0.052	-9999	-0.31	11	11

×

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	0.009	0.067	-10000	0	-0.49	9	9
SMAD2	0.021	0.048	0.24	1	-0.23	9	10
SMAD3	0.032	0.056	-10000	0	-0.39	2	2
SMAD3/SMAD4	0.033	0.069	-10000	0	-0.34	9	9
SMAD4/Ubc9/PIASy	0.027	0.052	-10000	0	-0.3	12	12
SMAD2/SMAD2/SMAD4	0.031	0.061	-10000	0	-0.27	1	1
PPM1A	0.016	0.026	-10000	0	-0.39	2	2
CALM1	0.018	0	-10000	0	-10000	0	0
SMAD2/SMAD4	0.024	0.056	0.2	1	-0.23	17	18
MAP3K1	-0.03	0.14	-10000	0	-0.42	58	58
TRAP-1/SMAD4	0.02	0.049	-10000	0	-0.37	8	8
MAPK3	0.016	0.026	-10000	0	-0.39	2	2
MAPK1	0.016	0.033	-10000	0	-0.52	2	2
NUP214	0.016	0.026	-10000	0	-0.39	2	2
CTDSP1	0.016	0.033	-10000	0	-0.52	2	2
CTDSP2	0.014	0.044	-10000	0	-0.41	5	5
CTDSPL	0.011	0.062	-10000	0	-0.52	7	7
KPNB1	0.012	0.057	-10000	0	-0.52	6	6
TGFBRAP1	0.017	0.012	-10000	0	-0.25	1	1
UBE2I	0.018	0	-10000	0	-10000	0	0
NUP153	0.016	0.024	-10000	0	-0.25	4	4
KPNA2	-0.001	0.084	-10000	0	-0.34	27	27
PIAS4	0.013	0.049	-10000	0	-0.43	6	6

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.018	0.036	-9999	-0.43	3	3
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.06	0.078	-9999	-0.38	4	4
ERC1	0.011	0.056	-9999	-0.42	8	8
RIP2/NOD2	-0.031	0.13	-9999	-0.37	66	66
NFKBIA	0.042	0.051	-9999	-0.54	3	3
BIRC2	0.016	0.02	-9999	-0.25	3	3
IKBKB	0.012	0.047	-9999	-0.31	10	10
RIPK2	0.013	0.04	-9999	-0.28	9	9
IKBKG	0.016	0.091	-9999	-0.51	5	5
IKK complex/A20	0.027	0.1	-9999	-0.44	9	9
NEMO/A20/RIP2	0.013	0.04	-9999	-0.28	9	9
XPO1	0.018	0	-9999	-10000	0	0
NEMO/ATM	0.024	0.088	-9999	-0.48	5	5
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.017	0.012	-9999	-0.25	1	1
Exportin 1/RanGTP	0.024	0.007	-9999	-10000	0	0
IKK complex/ELKS	-0.028	0.077	-9999	-0.46	8	8
BCL10/MALT1/TRAF6	0.031	0.041	-9999	-0.38	4	4
NOD2	-0.056	0.18	-9999	-0.46	81	81
NFKB1	0.019	0.025	-9999	-0.52	1	1
RELA	0.02	0.009	-9999	-10000	0	0
MALT1	0.011	0.053	-9999	-0.37	9	9
cIAP1/UbcH5C	0.025	0.014	-9999	-10000	0	0
ATM	0.017	0.012	-9999	-0.25	1	1
TNF/TNFR1A	0.009	0.071	-9999	-0.37	14	14
TRAF6	0.017	0.023	-9999	-0.52	1	1
PRKCA	0.014	0.033	-9999	-0.25	8	8
CHUK	0.005	0.081	-9999	-0.5	13	13
UBE2D3	0.018	0	-9999	-10000	0	0
TNF	-0.004	0.094	-9999	-0.36	31	31
NF kappa B1 p50/RelA	0.045	0.036	-9999	-0.28	6	6
BCL10	0.017	0.012	-9999	-0.25	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.042	0.051	-9999	-0.54	3	3
beta TrCP1/SCF ubiquitin ligase complex	0.018	0.036	-9999	-0.42	3	3
TNFRSF1A	0.016	0.033	-9999	-0.52	2	2
IKK complex	0.025	0.1	-9999	-0.46	9	9
CYLD	0.014	0.044	-9999	-0.41	5	5
IKK complex/PKC alpha	0.03	0.1	-9999	-0.49	7	7

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.015	0.047	-9999	-0.31	8	8
EFNA5	0.006	0.068	-9999	-0.35	17	17
FYN	0.015	0.055	-9999	-0.28	15	15
neuron projection morphogenesis	0.015	0.047	-9999	-0.31	8	8
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	0.015	0.047	-9999	-0.31	8	8
EPHA5	0.015	0.037	-9999	-0.39	4	4

×

Class I PI3K signaling events mediated by Akt

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.025	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.04	0.016	-10000	0	-0.27	1	1
CDKN1B	0.021	0.079	-10000	0	-0.37	8	8
CDKN1A	0.025	0.072	-10000	0	-0.44	6	6
FRAP1	0.018	0	-10000	0	-10000	0	0
PRKDC	0.012	0.045	-10000	0	-0.31	9	9
FOXO3	0.033	0.062	-10000	0	-0.46	6	6
AKT1	0.03	0.053	-10000	0	-0.43	6	6
BAD	0.017	0.023	-10000	0	-0.52	1	1
AKT3	0.007	0.046	-10000	0	-0.32	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.035	0.053	-10000	0	-0.39	7	7
AKT1/ASK1	0.018	0.081	-10000	0	-0.36	10	10
BAD/YWHAZ	0.035	0.018	-10000	0	-0.3	1	1
RICTOR	0.018	0	-10000	0	-10000	0	0
RAF1	0.017	0.012	-10000	0	-0.25	1	1
JNK cascade	-0.017	0.079	0.35	10	-10000	0	10
TSC1	0.036	0.051	-10000	0	-0.4	6	6
YWHAZ	0.017	0.017	-10000	0	-0.25	2	2
AKT1/RAF1	0.038	0.052	-10000	0	-0.4	6	6
EP300	0.014	0.047	-10000	0	-0.52	4	4
mol:GDP	0.03	0.053	-10000	0	-0.42	6	6
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.035	0.056	-10000	0	-0.44	6	6
YWHAQ	0.014	0.039	-10000	0	-0.36	5	5
TBC1D4	0.011	0.063	-10000	0	-0.3	19	19
MAP3K5	-0.022	0.13	-10000	0	-0.42	47	47
MAPKAP1	0.016	0.026	-10000	0	-0.39	2	2
negative regulation of cell cycle	-0.034	0.048	0.24	3	-10000	0	3
YWHAH	0.013	0.048	-10000	0	-0.47	5	5
AKT1S1	0.032	0.063	-10000	0	-0.4	9	9
CASP9	0.035	0.053	-10000	0	-0.39	7	7
YWHAB	0.015	0.037	-10000	0	-0.39	4	4
p27Kip1/KPNA1	0.03	0.076	-10000	0	-0.36	7	7
GBL	0.015	0.035	-10000	0	-0.43	3	3
PDK1/Src/Hsp90	0.031	0.039	-10000	0	-0.3	6	6
YWHAE	0.016	0.029	-10000	0	-0.34	3	3
SRC	0.015	0.035	-10000	0	-0.43	3	3
AKT2/p21CIP1	0.03	0.068	-10000	0	-0.39	6	6
KIAA1303	0.015	0.031	-10000	0	-0.32	4	4
mTOR/RHEB/GTP/Raptor/GBL	0.038	0.041	-10000	0	-0.39	4	4
CHUK	0.03	0.068	-10000	0	-0.42	7	7
BAD/BCL-XL	0.052	0.051	-10000	0	-0.37	6	6
mTORC2	0.043	0.025	-10000	0	-0.27	3	3
AKT2	0.019	0.017	-10000	0	-0.32	1	1
FOXO1-3a-4/14-3-3 family	0.046	0.064	-10000	0	-0.29	4	4
PDPK1	0.016	0.026	-10000	0	-0.39	2	2
MDM2	0.033	0.054	-10000	0	-0.4	6	6
MAPKKK cascade	-0.038	0.051	0.39	6	-10000	0	6
MDM2/Cbp/p300	0.047	0.061	-10000	0	-0.4	6	6
TSC1/TSC2	0.041	0.055	-10000	0	-0.42	6	6
proteasomal ubiquitin-dependent protein catabolic process	0.045	0.058	-10000	0	-0.38	6	6
glucose import	0.011	0.064	-10000	0	-0.26	21	21
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.044	0.053	-10000	0	-0.41	4	4
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.011	0.064	-10000	0	-0.26	21	21
GSK3A	0.036	0.051	-10000	0	-0.4	6	6
FOXO1	0.027	0.068	-10000	0	-0.39	7	7
GSK3B	0.036	0.051	-10000	0	-0.4	6	6
SFN	-0.015	0.12	-10000	0	-0.45	37	37
G1/S transition of mitotic cell cycle	0.042	0.05	-10000	0	-0.38	6	6
p27Kip1/14-3-3 family	0.034	0.063	-10000	0	-0.37	4	4
PRKACA	0.018	0	-10000	0	-10000	0	0
KPNA1	0.018	0	-10000	0	-10000	0	0
HSP90AA1	0.013	0.045	-10000	0	-0.39	6	6
YWHAG	0.017	0.017	-10000	0	-0.25	2	2
RHEB	0.016	0.026	-10000	0	-0.39	2	2
CREBBP	0.016	0.033	-10000	0	-0.52	2	2

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.005	0.06	-10000	0	-0.26	24	24
CLTC	0.025	0.05	-10000	0	-0.49	3	3
calcium ion-dependent exocytosis	0.021	0.039	-10000	0	-0.28	4	4
Dynamin 2/GTP	0.025	0.027	-10000	0	-0.28	2	2
EXOC4	0.016	0.033	-10000	0	-0.52	2	2
CD59	0.021	0.05	-10000	0	-0.42	4	4
CPE	-0.021	0.11	-10000	0	-0.32	53	53
CTNNB1	0.001	0.09	-10000	0	-0.45	19	19
membrane fusion	0.021	0.041	-10000	0	-0.39	2	2
CTNND1	0.029	0.029	-10000	0	-0.25	3	3
DNM2	0.017	0.012	-10000	0	-0.25	1	1
mol:PI-4-5-P2	0.027	0.039	-10000	0	-0.35	3	3
TSHR	0.014	0.048	-10000	0	-0.31	11	11
INS	0.02	0.026	-10000	0	-0.51	1	1
BIN1	0.014	0.04	-10000	0	-0.34	6	6
mol:Choline	0.021	0.041	-10000	0	-0.39	2	2
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.017	0.03	-10000	0	-0.31	2	2
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.016	0.033	-10000	0	-0.52	2	2
mol:Ca2+	0.025	0.027	-10000	0	-0.27	2	2
JUP	0.023	0.046	-10000	0	-0.48	3	3
ASAP2/amphiphysin II	0.019	0.029	-10000	0	-0.28	4	4
ARF6/GTP	0.012	0.024	-10000	0	-0.38	2	2
CDH1	0	0.078	-10000	0	-0.46	3	3
clathrin-independent pinocytosis	0.012	0.024	-10000	0	-0.38	2	2
MAPK8IP3	0.006	0.075	-10000	0	-0.48	12	12
positive regulation of endocytosis	0.012	0.024	-10000	0	-0.38	2	2
EXOC2	-0.004	0.085	-10000	0	-0.31	35	35
substrate adhesion-dependent cell spreading	0.023	0.078	-10000	0	-0.24	37	37
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.014	0.035	-10000	0	-0.3	6	6
regulation of calcium-dependent cell-cell adhesion	-0.011	0.077	0.44	4	-10000	0	4
positive regulation of phagocytosis	0.018	0.032	-10000	0	-0.31	5	5
ARF6/GTP/JIP3	0.016	0.051	-10000	0	-0.31	12	12
ACAP1	0.019	0.035	-10000	0	-0.35	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.016	0.046	-10000	0	-0.52	2	2
clathrin heavy chain/ACAP1	0.028	0.048	-10000	0	-0.46	3	3
JIP4/KLC1	0.031	0.027	-10000	0	-0.28	3	3
EXOC1	0.018	0	-10000	0	-10000	0	0
exocyst	0.023	0.078	-10000	0	-0.25	37	37
RALA/GTP	0.013	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.021	0.029	-10000	0	-0.31	3	3
receptor recycling	0.012	0.024	-10000	0	-0.38	2	2
CTNNA1	0.03	0.028	-10000	0	-0.25	3	3
NME1	0.017	0.03	-10000	0	-0.31	2	2
clathrin coat assembly	0.025	0.05	-10000	0	-0.48	3	3
IL2RA	0.008	0.069	-10000	0	-0.35	7	7
VAMP3	0.018	0.032	-10000	0	-0.31	5	5
GLUT4/clathrin heavy chain/ACAP1	-0.008	0.04	-10000	0	-0.43	3	3
EXOC6	-0.012	0.12	-10000	0	-0.5	30	30
PLD1	0.015	0.05	-10000	0	-0.29	11	11
PLD2	0.021	0.033	-10000	0	-0.26	6	6
EXOC5	0.016	0.033	-10000	0	-0.52	2	2
PIP5K1C	0.028	0.039	-10000	0	-0.35	3	3
SDC1	0.004	0.072	-10000	0	-0.39	4	4
ARF6/GDP	0.018	0.03	-10000	0	-0.31	2	2
EXOC7	0.018	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.013	0.079	-10000	0	-0.52	3	3
mol:Phosphatidic acid	0.021	0.041	-10000	0	-0.39	2	2
endocytosis	-0.019	0.029	0.28	4	-10000	0	4
SCAMP2	0.015	0.035	-10000	0	-0.43	3	3
ADRB2	0.001	0.096	-10000	0	-0.45	8	8
EXOC3	0.017	0.012	-10000	0	-0.25	1	1
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.027	0.028	-10000	0	-0.27	2	2
KLC1	0.018	0	-10000	0	-10000	0	0
AVPR2	0.03	0.049	-10000	0	-0.45	3	3
RALA	0.018	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.022	0.076	-10000	0	-0.58	2	2

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.016	0.024	-9999	-0.25	4	4
CDC42/GTP	0.016	0.067	-9999	-0.33	5	5
PLCG1	0.014	0.07	-9999	-0.26	13	13
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.006	0.075	-9999	-0.48	12	12
GNAI3	0.018	0	-9999	-10000	0	0
G12/G13	0.021	0.039	-9999	-0.37	4	4
cell migration	0.016	0.065	-9999	-0.32	5	5
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
MAPK3	0.014	0.069	-9999	-0.32	6	6
MAPK1	0.014	0.07	-9999	-0.31	7	7
S1P/S1P5/Gi	0.008	0.072	-9999	-0.29	12	12
GNAI1	-0.017	0.12	-9999	-0.38	46	46
CDC42/GDP	0.013	0	-9999	-10000	0	0
S1P/S1P5/G12	0.012	0	-9999	-10000	0	0
RHOA	0.017	0.056	-9999	-0.3	14	14
S1P/S1P4/Gi	0.008	0.072	-9999	-0.29	12	12
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.001	0.088	-9999	-0.44	19	19
S1P/S1P4/G12/G13	0.019	0.03	-9999	-0.28	4	4
GNA12	0.018	0	-9999	-10000	0	0
GNA13	0.011	0.055	-9999	-0.36	10	10
CDC42	0.018	0	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.038	0.06	-9999	-0.35	4	4
CaM/Ca2+	0.013	0	-9999	-10000	0	0
AKT1	0.011	0.053	-9999	-0.37	9	9
AKT2	0.017	0.012	-9999	-0.25	1	1
STXBP4	0.008	0.06	-9999	-0.32	15	15
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	0.033	0.053	-9999	-0.26	3	3
YWHAZ	0.017	0.017	-9999	-0.25	2	2
CALM1	0.018	0	-9999	-10000	0	0
YWHAQ	0.014	0.039	-9999	-0.36	5	5
TBC1D4	0.004	0.086	-9999	-0.38	21	21
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0.013	0.048	-9999	-0.47	5	5
YWHAB	0.015	0.037	-9999	-0.39	4	4
SNARE/Synip	0.029	0.042	-9999	-0.3	6	6
YWHAG	0.017	0.017	-9999	-0.25	2	2
ASIP	0	0	-9999	-10000	0	0
PRKCI	0.002	0.085	-9999	-0.43	18	18
AS160/CaM/Ca2+	0.013	0	-9999	-10000	0	0
RHOQ	0.012	0.053	-9999	-0.48	6	6
GYS1	0.031	0.027	-9999	-0.26	4	4
PRKCZ	0	0	-9999	-10000	0	0
TRIP10	0.013	0.048	-9999	-0.47	5	5
TC10/GTP/CIP4/Exocyst	0.018	0.045	-9999	-0.31	9	9
AS160/14-3-3	0.025	0.066	-9999	-0.39	1	1
VAMP2	0.017	0.023	-9999	-0.52	1	1
SLC2A4	0.033	0.056	-9999	-0.28	3	3
STX4	0.017	0.023	-9999	-0.52	1	1
GSK3B	0.026	0.032	-9999	-0.31	4	4
SFN	-0.015	0.12	-9999	-0.45	37	37
LNPEP	0.01	0.06	-9999	-0.43	9	9
YWHAE	0.016	0.029	-9999	-0.34	3	3

×

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	0.033	0.064	-10000	0	-0.29	16	16
Ran/GTP/Exportin 1/HDAC1	-0.001	0.011	-10000	0	-0.22	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.039	0.064	-10000	0	-0.27	14	14
SUMO1	0.018	0	-10000	0	-10000	0	0
ZFPM1	0.009	0.068	-10000	0	-0.47	10	10
NPC/RanGAP1/SUMO1/Ubc9	0.023	0.013	-10000	0	-0.2	1	1
FKBP3	0.013	0.048	-10000	0	-0.47	5	5
Histones	0.043	0.05	-10000	0	-0.28	2	2
YY1/LSF	0.02	0.056	-10000	0	-0.26	20	20
SMG5	0.016	0.029	-10000	0	-0.34	3	3
RAN	0.017	0.012	-10000	0	-0.25	1	1
I kappa B alpha/HDAC3	0.025	0.056	-10000	0	-0.24	19	19
I kappa B alpha/HDAC1	0.027	0.051	-10000	0	-0.31	6	6
SAP18	0.018	0	-10000	0	-10000	0	0
RELA	0.03	0.051	-10000	0	-10000	0	0
HDAC1/Smad7	0.035	0.022	-10000	0	-0.3	2	2
RANGAP1	0.014	0.037	-10000	0	-0.29	7	7
HDAC3/TR2	0.026	0.053	-10000	0	-0.28	9	9
NuRD/MBD3 Complex	0.045	0.038	-10000	0	-0.27	2	2
NF kappa B1 p50/RelA	0.035	0.049	-10000	0	-0.24	1	1
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.007	0.093	-10000	0	-0.31	40	40
GATA1	0.018	0	-10000	0	-10000	0	0
Mad/Max	0.024	0.021	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.053	0.054	-10000	0	-0.48	2	2
RBBP7	0.01	0.051	-10000	0	-0.3	13	13
NPC	0.01	0.008	-10000	0	-10000	0	0
RBBP4	0.016	0.026	-10000	0	-0.39	2	2
MAX	0.018	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.015	0.035	-10000	0	-0.43	3	3
NFKBIA	0.02	0.054	-10000	0	-0.36	5	5
KAT2B	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.041	0.036	-10000	0	-10000	0	0
SIN3 complex	0.042	0.032	-10000	0	-0.27	5	5
SMURF1	0.018	0	-10000	0	-10000	0	0
CHD3	0.015	0.037	-10000	0	-0.39	4	4
SAP30	0.012	0.053	-10000	0	-0.48	6	6
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.016	0.033	-10000	0	-0.52	2	2
YY1/HDAC3	0.032	0.046	-10000	0	-0.29	2	2
YY1/HDAC2	0.022	0.045	-10000	0	-0.25	11	11
YY1/HDAC1	0.027	0.036	-10000	0	-0.23	10	10
NuRD/MBD2 Complex (MeCP1)	0.044	0.038	-10000	0	-0.27	2	2
PPARG	0.006	0.096	-10000	0	-0.3	38	38
HDAC8/hEST1B	0.034	0.027	-10000	0	-0.3	3	3
UBE2I	0.018	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.015	0.035	-10000	0	-0.43	3	3
TNFRSF1A	0.016	0.033	-10000	0	-0.52	2	2
HDAC3/SMRT (N-CoR2)	0.03	0.041	-10000	0	-0.32	2	2
MBD3L2	0.007	0.072	-10000	0	-0.45	12	12
ubiquitin-dependent protein catabolic process	0.034	0.022	-10000	0	-0.3	2	2
CREBBP	0.016	0.033	-10000	0	-0.52	2	2
NuRD/MBD3/MBD3L2 Complex	0.049	0.051	-10000	0	-0.32	2	2
HDAC1	0.017	0.023	-10000	0	-0.52	1	1
HDAC3	0.023	0.045	-10000	0	-0.36	2	2
HDAC2	0.009	0.053	-10000	0	-0.29	15	15
YY1	0.021	0.038	-10000	0	-0.27	9	9
HDAC8	0.016	0.033	-10000	0	-0.52	2	2
SMAD7	0.016	0.026	-10000	0	-0.39	2	2
NCOR2	0.018	0	-10000	0	-10000	0	0
MXD1	0.014	0.031	-10000	0	-0.25	7	7
STAT3	0.024	0.044	-10000	0	-0.31	9	9
NFKB1	0.017	0.023	-10000	0	-0.52	1	1
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.017	0.017	-10000	0	-0.25	2	2
YY1/LSF/HDAC1	0.03	0.054	-10000	0	-0.26	12	12
YY1/SAP30/HDAC1	0.033	0.047	-10000	0	-0.3	6	6
EP300	0.014	0.047	-10000	0	-0.52	4	4
STAT3 (dimer non-phopshorylated)	0.024	0.044	-10000	0	-0.31	9	9
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.054	-10000	0	-0.36	5	5
histone deacetylation	0.044	0.038	-10000	0	-0.27	2	2
STAT3 (dimer non-phopshorylated)/HDAC3	0.035	0.051	-10000	0	-0.32	3	3
nuclear export	-0.033	0.027	0.3	3	-10000	0	3
PRKACA	0.018	0	-10000	0	-10000	0	0
GATAD2B	0.017	0.023	-10000	0	-0.52	1	1
GATAD2A	0.014	0.037	-10000	0	-0.29	7	7
GATA2/HDAC3	0.017	0.069	-10000	0	-0.32	12	12
GATA1/HDAC1	0.026	0.017	-10000	0	-0.37	1	1
GATA1/HDAC3	0.03	0.041	-10000	0	-0.32	2	2
CHD4	0.017	0.023	-10000	0	-0.52	1	1
TNF-alpha/TNFR1A	0.009	0.071	-10000	0	-0.37	14	14
SIN3/HDAC complex/Mad/Max	0.046	0.033	-10000	0	-10000	0	0
NuRD Complex	0.052	0.044	-10000	0	-0.32	2	2
positive regulation of chromatin silencing	0.04	0.049	-10000	0	-0.27	2	2
SIN3B	0.017	0.012	-10000	0	-0.25	1	1
MTA2	0.014	0.044	-10000	0	-0.41	5	5
SIN3A	0.018	0	-10000	0	-10000	0	0
XPO1	0.018	0	-10000	0	-10000	0	0
SUMO1/HDAC1	0.036	0.018	-10000	0	-0.24	1	1
HDAC complex	0.035	0.045	-10000	0	-0.26	7	7
GATA1/Fog1	0.02	0.049	-10000	0	-0.37	8	8
FKBP25/HDAC1/HDAC2	0.027	0.047	-10000	0	-0.3	8	8
TNF	-0.004	0.094	-10000	0	-0.36	31	31
negative regulation of cell growth	0.046	0.033	-10000	0	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.044	0.038	-10000	0	-0.27	2	2
Ran/GTP/Exportin 1	0.039	0.013	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.031	0.065	-10000	0	-0.29	16	16
SIN3/HDAC complex/NCoR1	0.043	0.035	-10000	0	-10000	0	0
TFCP2	0.006	0.077	-10000	0	-0.52	11	11
NR2C1	0.011	0.062	-10000	0	-0.52	7	7
MBD3	0.018	0	-10000	0	-10000	0	0
MBD2	0.017	0.017	-10000	0	-0.25	2	2

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	0.024	0.045	-10000	0	-0.29	8	8
MAPK9	-0.005	0.07	-10000	0	-0.33	23	23
adrenocorticotropin secretion	0.005	0.042	-10000	0	-0.2	18	18
GNB1/GNG2	0.02	0.037	-10000	0	-0.31	6	6
GNB1	0.013	0.052	-10000	0	-0.52	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	0.01	0.005	-10000	0	-10000	0	0
Gs family/GTP	0.008	0.028	-10000	0	-0.17	11	11
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	0.001	0.007	0.048	11	-10000	0	11
GNAL	0.011	0.052	-10000	0	-0.33	11	11
GNG2	0.016	0.029	-10000	0	-0.34	3	3
CRH	0.007	0.06	-10000	0	-0.3	18	18
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.008	0.026	-10000	0	-0.33	3	3
MAPK11	0.01	0	-10000	0	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.023	0.017	-10000	0	-0.2	2	2
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.02	0.019	-10000	0	-0.27	1	1
AP2	0.021	0.04	-10000	0	-0.36	5	5
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.019	0.041	-10000	0	-0.31	8	8
CLTB	0.015	0.035	-10000	0	-0.43	3	3
coatomer protein complex/ARF1/GTP/ER cargo protein	0.027	0.02	-10000	0	-0.24	3	3
CD4	0.018	0	-10000	0	-10000	0	0
CLTA	0.018	0	-10000	0	-10000	0	0
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
ARFGAP1	0.012	0.011	-10000	0	-0.17	2	2
mol:PI-4-5-P2	0.012	0.025	0.15	8	-0.18	4	12
ARF1/GTP	-0.001	0.015	-10000	0	-0.29	1	1
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.028	0.014	-10000	0	-0.2	1	1
mol:Choline	0.011	0.025	0.15	8	-0.19	4	12
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.016	0.024	-10000	0	-0.53	1	1
DDEF1	0.012	0.025	0.15	8	-0.19	4	12
ARF1/GDP	0.009	0.012	-10000	0	-10000	0	0
AP2M1	0.013	0.049	-10000	0	-0.43	6	6
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.017	0.013	-10000	0	-0.28	1	1
Rac/GTP	0.014	0.001	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.028	0.02	-10000	0	-0.26	2	2
ARFIP2	0.008	0.063	-10000	0	-0.47	9	9
COPA	0.018	0	-10000	0	-10000	0	0
RAC1	0.018	0	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.026	0.017	-10000	0	-0.2	2	2
ARF1/GTP/ARHGAP10	0.01	0.014	-10000	0	-0.32	1	1
GGA3	0.016	0.026	-10000	0	-0.39	2	2
ARF1/GTP/Membrin	0.017	0.015	-10000	0	-0.27	1	1
AP2A1	0.016	0.024	-10000	0	-0.25	4	4
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.028	0.021	-10000	0	-0.23	3	3
ARF1/GDP/Membrin	0.019	0.015	-10000	0	-0.26	1	1
Arfaptin 2/Rac/GDP	0.018	0.041	-10000	0	-0.31	8	8
CYTH2	0.001	0.002	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.021	0.022	-10000	0	-0.32	2	2
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.013	0	-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	0.036	0.036	-10000	0	-0.36	3	3
PLD2	0.011	0.026	0.15	8	-0.19	4	12
ARF-GAP1/v-SNARE	0.012	0.011	-10000	0	-0.17	2	2
PIP5K1A	0.012	0.025	0.15	8	-0.18	4	12
ARF1/GTP/Membrin/GBF1/p115	0.018	0.016	-10000	0	-0.26	1	1
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.011	0.025	0.15	8	-0.19	4	12
KDEL Receptor/Ligand/ARF-GAP1	0.012	0.011	-10000	0	-0.17	2	2
GOSR2	0.015	0.014	-10000	0	-10000	0	0
USO1	0.015	0.013	-10000	0	-10000	0	0
GBF1	0.014	0.023	-10000	0	-0.41	1	1
ARF1/GTP/Arfaptin 2	0.018	0.044	-10000	0	-0.31	9	9
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.032	0.035	-10000	0	-0.3	5	5

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.017	0.023	-9999	-0.52	1	1
Ran/GTP/Exportin 1/HDAC4	-0.001	0.012	-9999	-0.25	1	1
MDM2/SUMO1	0.033	0.024	-9999	-10000	0	0
HDAC4	0.017	0.023	-9999	-0.52	1	1
Ran/GTP/Exportin 1/HDAC1	-0.001	0.011	-9999	-0.2	1	1
SUMO1	0.018	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.018	0.015	-9999	-0.24	1	1
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.029	0.013	-9999	-0.18	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.017	0.012	-9999	-0.25	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.017	0.017	-9999	-0.25	2	2
SUMO1/HDAC4	0.036	0.019	-9999	-0.31	1	1
SUMO1/HDAC1	0.036	0.018	-9999	-0.24	1	1
RANGAP1	0.014	0.037	-9999	-0.29	7	7
MDM2/SUMO1/SUMO1	0.04	0.031	-9999	-0.27	2	2
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.023	0.013	-9999	-0.2	1	1
Ran/GTP	0.031	0.013	-9999	-0.18	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.011	0.044	-9999	-0.25	14	14
UBE2I	0.018	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.037	0.013	-9999	-10000	0	0
NPC	0.01	0.008	-9999	-10000	0	0
PIAS2	0.015	0.035	-9999	-0.43	3	3
PIAS1	0.017	0.012	-9999	-0.25	1	1
EntrezGene:9972	0	0	-9999	-10000	0	0