Glioblastoma Multiforme: PARADIGM pathway analysis of mRNA expression and copy number data

Pathway.Name	Avg.Num.Perturbations
HIF-1-alpha transcription factor network	127
FOXM1 transcription factor network	110
Angiopoietin receptor Tie2-mediated signaling	88
Endothelins	86
PDGFR-alpha signaling pathway	79
TCGA08_rtk_signaling	74
TCGA08_p53	73
Thromboxane A2 receptor signaling	72
HIF-2-alpha transcription factor network	72
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	72

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
HIF-1-alpha transcription factor network	127	9660	76	-0.081	0.1	1000	-1000	-0.006	-1000
FOXM1 transcription factor network	110	5635	51	-0.32	0.062	1000	-1000	-0.038	-1000
Angiopoietin receptor Tie2-mediated signaling	88	7822	88	-0.29	0.053	1000	-1000	-0.047	-1000
Endothelins	86	8305	96	-0.14	0.036	1000	-1000	-0.025	-1000
PDGFR-alpha signaling pathway	79	3482	44	-0.093	0.036	1000	-1000	-0.02	-1000
TCGA08_rtk_signaling	74	1944	26	-0.027	0.095	1000	-1000	-0.015	-1000
TCGA08_p53	73	515	7	-0.001	0.034	1000	-1000	-0.01	-1000
Thromboxane A2 receptor signaling	72	7617	105	-0.068	0.044	1000	-1000	-0.027	-1000
HIF-2-alpha transcription factor network	72	3108	43	-0.078	0.047	1000	-1000	-0.048	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	72	2386	33	-0.075	0.068	1000	-1000	-0.013	-1000
EGFR-dependent Endothelin signaling events	71	1500	21	-0.005	0.092	1000	-1000	-0.009	-1000
Effects of Botulinum toxin	70	1835	26	-0.007	0.053	1000	-1000	-0.011	-1000
Canonical Wnt signaling pathway	67	3418	51	-0.1	0.074	1000	-1000	-0.023	-1000
Syndecan-3-mediated signaling events	66	2316	35	-0.072	0.08	1000	-1000	-0.026	-1000
Wnt signaling	66	463	7	-0.006	0.037	1000	-1000	-0.001	-1000
Arf6 signaling events	65	4078	62	-0.005	0.093	1000	-1000	-0.003	-1000
Ras signaling in the CD4+ TCR pathway	65	1111	17	-0.001	0.043	1000	-1000	-0.002	-1000
LPA receptor mediated events	61	6232	102	-0.13	0.037	1000	-1000	-0.056	-1000
TCGA08_retinoblastoma	61	495	8	-0.046	0.056	1000	-1000	-0.002	-1000
Syndecan-4-mediated signaling events	60	4029	67	-0.14	0.036	1000	-1000	-0.03	-1000
S1P5 pathway	58	1000	17	-0.009	0.036	1000	-1000	-0.01	-1000
Nongenotropic Androgen signaling	58	3034	52	-0.084	0.058	1000	-1000	-0.02	-1000
S1P4 pathway	58	1474	25	-0.013	0.041	1000	-1000	-0.01	-1000
Syndecan-1-mediated signaling events	55	1889	34	-0.003	0.035	1000	-1000	-0.021	-1000
Fc-epsilon receptor I signaling in mast cells	55	5370	97	-0.13	0.048	1000	-1000	-0.039	-1000
JNK signaling in the CD4+ TCR pathway	53	906	17	-0.14	0.063	1000	-1000	-0.009	-1000
amb2 Integrin signaling	53	4352	82	-0.016	0.076	1000	-1000	-0.015	-1000
IL2 signaling events mediated by STAT5	53	1176	22	-0.072	0.042	1000	-1000	-0.019	-1000
Syndecan-2-mediated signaling events	52	3611	69	-0.026	0.037	1000	-1000	-0.024	-1000
EPO signaling pathway	52	2905	55	-0.001	0.082	1000	-1000	-0.011	-1000
IL23-mediated signaling events	52	3142	60	-0.064	0.15	1000	-1000	-0.024	-1000
Glypican 2 network	51	206	4	0	0.007	1000	-1000	0	-1000
Osteopontin-mediated events	50	1901	38	-0.074	0.05	1000	-1000	-0.016	-1000
PLK2 and PLK4 events	48	145	3	-0.011	0.035	1000	-1000	-0.014	-1000
Signaling events mediated by PTP1B	46	3561	76	-0.032	0.06	1000	-1000	-0.037	-1000
FoxO family signaling	46	2963	64	-0.17	0.053	1000	-1000	-0.035	-1000
BCR signaling pathway	46	4576	99	-0.06	0.05	1000	-1000	-0.035	-1000
E-cadherin signaling in keratinocytes	46	1988	43	-0.039	0.064	1000	-1000	-0.016	-1000
Presenilin action in Notch and Wnt signaling	45	2799	61	-0.082	0.08	1000	-1000	-0.029	-1000
Ephrin B reverse signaling	44	2114	48	-0.065	0.068	1000	-1000	-0.048	-1000
IL2 signaling events mediated by PI3K	44	2596	58	-0.069	0.038	1000	-1000	-0.019	-1000
EPHB forward signaling	44	3751	85	-0.053	0.082	1000	-1000	-0.043	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	44	3030	68	-0.1	0.046	1000	-1000	-0.026	-1000
Regulation of nuclear SMAD2/3 signaling	43	5912	136	-0.21	0.2	1000	-1000	-0.045	-1000
Noncanonical Wnt signaling pathway	43	1120	26	-0.037	0.037	1000	-1000	-0.035	-1000
Arf6 downstream pathway	42	1838	43	-0.025	0.05	1000	-1000	-0.028	-1000
Reelin signaling pathway	42	2380	56	-0.014	0.067	1000	-1000	-0.017	-1000
Signaling events mediated by VEGFR1 and VEGFR2	42	5289	125	-0.045	0.06	1000	-1000	-0.041	-1000
ErbB2/ErbB3 signaling events	41	2691	65	-0.044	0.036	1000	-1000	-0.039	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	41	2250	54	-0.037	0.079	1000	-1000	-0.025	-1000
Paxillin-dependent events mediated by a4b1	41	1504	36	-0.053	0.052	1000	-1000	-0.045	-1000
Sphingosine 1-phosphate (S1P) pathway	40	1135	28	-0.011	0.036	1000	-1000	-0.014	-1000
BMP receptor signaling	40	3313	81	-0.033	0.054	1000	-1000	-0.007	-1000
mTOR signaling pathway	40	2142	53	-0.031	0.046	1000	-1000	-0.021	-1000
IL6-mediated signaling events	40	3003	75	-0.076	0.11	1000	-1000	-0.024	-1000
Class I PI3K signaling events	40	2980	73	-0.05	0.068	1000	-1000	-0.019	-1000
IL12-mediated signaling events	39	3415	87	-0.11	0.095	1000	-1000	-0.024	-1000
Paxillin-independent events mediated by a4b1 and a4b7	39	1472	37	-0.034	0.082	1000	-1000	-0.012	-1000
IL1-mediated signaling events	39	2467	62	-0.046	0.074	1000	-1000	-0.039	-1000
p38 MAPK signaling pathway	39	1721	44	0	0.044	1000	-1000	-0.01	-1000
Glypican 1 network	38	1866	48	-0.032	0.052	1000	-1000	-0.033	-1000
PLK1 signaling events	38	3261	85	-0.05	0.054	1000	-1000	-0.021	-1000
FAS signaling pathway (CD95)	38	1810	47	-0.17	0.048	1000	-1000	-0.033	-1000
Stabilization and expansion of the E-cadherin adherens junction	38	2828	74	-0.13	0.079	1000	-1000	-0.046	-1000
Class I PI3K signaling events mediated by Akt	37	2558	68	-0.029	0.064	1000	-1000	-0.014	-1000
S1P1 pathway	37	1342	36	-0.004	0.055	1000	-1000	-0.018	-1000
PDGFR-beta signaling pathway	37	3614	97	-0.052	0.066	1000	-1000	-0.041	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	36	3104	85	-0.12	0.11	1000	-1000	-0.018	-1000
IFN-gamma pathway	36	2508	68	-0.04	0.064	1000	-1000	-0.033	-1000
Regulation of p38-alpha and p38-beta	36	1947	54	0	0.047	1000	-1000	-0.014	-1000
IGF1 pathway	36	2070	57	-0.046	0.067	1000	-1000	-0.029	-1000
Neurotrophic factor-mediated Trk receptor signaling	36	4379	120	-0.035	0.087	1000	-1000	-0.027	-1000
Hedgehog signaling events mediated by Gli proteins	35	2330	65	-0.017	0.057	1000	-1000	-0.02	-1000
TCR signaling in naïve CD8+ T cells	35	3296	93	-0.34	0.39	1000	-1000	-0.025	-1000
a4b1 and a4b7 Integrin signaling	34	171	5	0.026	0.052	1000	-1000	0.032	-1000
Signaling events regulated by Ret tyrosine kinase	34	2833	82	-0.058	0.062	1000	-1000	-0.023	-1000
Alternative NF-kappaB pathway	34	449	13	0	0.065	1000	-1000	0	-1000
Plasma membrane estrogen receptor signaling	33	2884	86	-0.067	0.052	1000	-1000	-0.033	-1000
IL4-mediated signaling events	32	2992	91	-0.32	0.063	1000	-1000	-0.054	-1000
E-cadherin signaling in the nascent adherens junction	32	2436	76	-0.041	0.091	1000	-1000	-0.034	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	32	2511	78	-0.022	0.073	1000	-1000	-0.031	-1000
Retinoic acid receptors-mediated signaling	31	1829	58	-0.054	0.059	1000	-1000	-0.016	-1000
Caspase cascade in apoptosis	30	2261	74	-0.08	0.066	1000	-1000	-0.032	-1000
ErbB4 signaling events	30	2099	69	-0.07	0.064	1000	-1000	-0.027	-1000
Aurora A signaling	30	1800	60	-0.028	0.058	1000	-1000	-0.016	-1000
Signaling events mediated by HDAC Class III	30	1208	40	-0.048	0.048	1000	-1000	-0.046	-1000
Signaling mediated by p38-gamma and p38-delta	30	451	15	-0.025	0.036	1000	-1000	-0.023	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	30	1362	45	-0.034	0.076	1000	-1000	-0.028	-1000
Insulin Pathway	30	2238	74	-0.034	0.084	1000	-1000	-0.032	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	29	673	23	-0.018	0.054	1000	-1000	-0.007	-1000
p75(NTR)-mediated signaling	29	3668	125	-0.023	0.088	1000	-1000	-0.039	-1000
Integrins in angiogenesis	29	2514	84	-0.046	0.071	1000	-1000	-0.02	-1000
Regulation of Telomerase	29	3005	102	-0.028	0.076	1000	-1000	-0.025	-1000
Signaling events mediated by PRL	29	1016	34	-0.036	0.047	1000	-1000	-0.027	-1000
Aurora B signaling	29	1961	67	-0.033	0.063	1000	-1000	-0.014	-1000
Visual signal transduction: Cones	28	1093	38	-0.014	0.059	1000	-1000	-0.011	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	28	2387	83	-0.036	0.068	1000	-1000	-0.014	-1000
S1P3 pathway	28	1211	42	-0.02	0.037	1000	-1000	-0.022	-1000
TRAIL signaling pathway	27	1320	48	-0.034	0.087	1000	-1000	-0.015	-1000
BARD1 signaling events	26	1532	57	-0.064	0.085	1000	-1000	-0.058	-1000
Glucocorticoid receptor regulatory network	26	3014	114	-0.12	0.064	1000	-1000	-0.043	-1000
Coregulation of Androgen receptor activity	24	1833	76	-0.011	0.07	1000	-1000	-0.01	-1000
Insulin-mediated glucose transport	24	797	32	-0.016	0.042	1000	-1000	-0.015	-1000
Nectin adhesion pathway	24	1563	63	-0.01	0.083	1000	-1000	-0.024	-1000
Signaling events mediated by HDAC Class I	23	2428	104	-0.029	0.066	1000	-1000	-0.027	-1000
Regulation of Androgen receptor activity	23	1649	70	-0.032	0.067	1000	-1000	-0.021	-1000
RXR and RAR heterodimerization with other nuclear receptor	22	1144	52	-0.044	0.1	1000	-1000	-0.019	-1000
IL27-mediated signaling events	22	1161	51	-0.016	0.063	1000	-1000	-0.03	-1000
Ceramide signaling pathway	21	1620	76	-0.04	0.07	1000	-1000	-0.015	-1000
E-cadherin signaling events	21	109	5	0.033	0.063	1000	-1000	0.032	-1000
Atypical NF-kappaB pathway	20	650	31	-0.021	0.037	1000	-1000	-0.014	-1000
Calcium signaling in the CD4+ TCR pathway	20	648	31	-0.021	0.09	1000	-1000	-0.022	-1000
Signaling events mediated by HDAC Class II	19	1481	75	-0.03	0.093	1000	-1000	-0.026	-1000
Cellular roles of Anthrax toxin	19	762	39	-0.068	0.036	1000	-1000	-0.01	-1000
Signaling mediated by p38-alpha and p38-beta	19	836	44	-0.015	0.084	1000	-1000	-0.018	-1000
Arf6 trafficking events	19	1407	71	-0.038	0.046	1000	-1000	-0.034	-1000
VEGFR1 specific signals	19	1085	56	-0.032	0.042	1000	-1000	-0.022	-1000
Canonical NF-kappaB pathway	18	720	39	-0.033	0.065	1000	-1000	-0.017	-1000
Circadian rhythm pathway	18	409	22	-0.01	0.056	1000	-1000	-0.025	-1000
ceramide signaling pathway	18	882	49	-0.015	0.053	1000	-1000	-0.015	-1000
Arf1 pathway	18	1023	54	-0.075	0.044	1000	-1000	-0.012	-1000
Nephrin/Neph1 signaling in the kidney podocyte	17	579	34	-0.054	0.095	1000	-1000	-0.04	-1000
Signaling events mediated by the Hedgehog family	17	923	52	-0.015	0.09	1000	-1000	-0.02	-1000
Rapid glucocorticoid signaling	16	322	20	-0.011	0.036	1000	-1000	-0.01	-1000
Sumoylation by RanBP2 regulates transcriptional repression	15	412	27	-0.033	0.077	1000	-1000	-0.029	-1000
FOXA2 and FOXA3 transcription factor networks	11	544	46	0	0.1	1000	-1000	-0.044	-1000
Aurora C signaling	10	75	7	0	0.063	1000	-1000	-0.006	-1000
Class IB PI3K non-lipid kinase events	9	27	3	-0.036	0.036	1000	-1000	-0.033	-1000
LPA4-mediated signaling events	8	99	12	-0.017	0.017	1000	-1000	-0.012	-1000
Visual signal transduction: Rods	8	427	52	-0.034	0.085	1000	-1000	-0.01	-1000
Ephrin A reverse signaling	2	17	7	-0.019	0.048	1000	-1000	-0.011	-1000
Total	5195	292535	7203	-7	8.6	131000	-131000	-3	-131000

HIF-1-alpha transcription factor network

Figure S1. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S1. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	0.027	0.46	0.62	84	-0.76	87	171
HDAC7	-0.001	0.005	-10000	0	-0.051	3	3
HIF1A/ARNT/Cbp/p300/Src-1	-0.029	0.39	0.59	36	-0.69	78	114
SMAD4	0.033	0.014	0.08	10	-10000	0	10
ID2	0.046	0.48	0.62	105	-0.76	85	190
AP1	0.013	0.083	-10000	0	-0.18	73	73
ABCG2	0.013	0.47	0.63	89	-0.76	89	178
HIF1A	0.044	0.13	0.23	83	-0.15	68	151
TFF3	0.04	0.47	0.63	94	-0.74	86	180
GATA2	0.038	0.014	0.076	22	-0.077	2	24
AKT1	0.052	0.14	0.25	90	-0.19	43	133
response to hypoxia	0.012	0.09	0.17	85	-0.12	51	136
MCL1	0.052	0.48	0.63	106	-0.75	87	193
NDRG1	-0.003	0.46	0.62	69	-0.76	90	159
SERPINE1	-0.068	0.39	0.58	36	-0.78	80	116
FECH	0.042	0.47	0.63	93	-0.74	86	179
FURIN	0.052	0.48	0.63	102	-0.75	86	188
NCOA2	0.037	0.006	-10000	0	-10000	0	0
EP300	0.073	0.18	0.36	96	-0.31	29	125
HMOX1	-0.022	0.46	0.63	64	-0.79	87	151
BHLHE40	-0.056	0.41	0.55	74	-0.72	91	165
BHLHE41	-0.056	0.41	0.55	74	-0.72	91	165
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.07	0.18	0.36	47	-0.23	37	84
ENG	0.03	0.15	0.3	51	-0.25	19	70
JUN	0.035	0.013	-10000	0	-0.002	43	43
RORA	0.024	0.47	0.62	86	-0.75	88	174
ABCB1	-0.057	0.22	-10000	0	-0.84	29	29
TFRC	0.03	0.47	0.62	97	-0.74	90	187
CXCR4	0.012	0.47	0.62	84	-0.76	92	176
TF	-0.081	0.41	0.64	40	-0.75	92	132
CITED2	0.011	0.46	0.61	85	-0.75	89	174
HIF1A/ARNT	-0.077	0.45	0.66	20	-0.87	78	98
LDHA	-0.066	0.28	-10000	0	-0.97	40	40
ETS1	0.056	0.48	0.64	102	-0.75	87	189
PGK1	0.045	0.48	0.63	101	-0.77	87	188
NOS2	-0.056	0.41	0.55	74	-0.72	91	165
ITGB2	0.003	0.46	0.61	86	-0.77	90	176
ALDOA	0.054	0.48	0.64	100	-0.76	86	186
Cbp/p300/CITED2	-0.023	0.46	0.61	67	-0.8	86	153
FOS	0.026	0.018	-10000	0	0	163	163
HK2	0.055	0.48	0.63	104	-0.75	87	191
SP1	0.033	0.059	0.11	38	-0.15	40	78
GCK	0.1	0.24	0.56	59	-0.48	11	70
HK1	-0.001	0.45	0.63	78	-0.75	86	164
NPM1	0.05	0.48	0.63	100	-0.76	84	184
EGLN1	0.047	0.47	0.63	97	-0.75	85	182
CREB1	0.032	0.034	-10000	0	-0.1	30	30
PGM1	0.049	0.48	0.64	100	-0.75	87	187
SMAD3	0.037	0.008	0.08	10	-10000	0	10
EDN1	0.053	0.22	0.47	28	-0.54	20	48
IGFBP1	-0.011	0.42	0.64	57	-0.76	74	131
VEGFA	-0.014	0.34	0.49	82	-0.57	87	169
HIF1A/JAB1	0.043	0.1	0.21	43	-0.19	17	60
CP	-0.036	0.45	0.61	65	-0.76	93	158
CXCL12	-0.039	0.41	0.62	47	-0.76	83	130
COPS5	0.037	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4	0.039	0.053	0.14	5	-0.14	35	40
BNIP3	-0.008	0.45	0.65	70	-0.76	84	154
EGLN3	0.004	0.45	0.62	75	-0.75	86	161
CA9	-0.017	0.43	0.6	64	-0.75	84	148
TERT	0.048	0.48	0.63	101	-0.75	86	187
ENO1	0.045	0.48	0.64	98	-0.76	85	183
PFKL	0.053	0.48	0.64	102	-0.76	85	187
NCOA1	0.033	0.011	-10000	0	0	49	49
ADM	-0.021	0.46	0.62	72	-0.76	95	167
ARNT	0.048	0.13	0.24	84	-0.14	65	149
HNF4A	0.037	0.012	0.084	6	-10000	0	6
ADFP	-0.03	0.44	0.63	56	-0.76	90	146
SLC2A1	0.013	0.37	0.54	75	-0.6	84	159
LEP	0.006	0.43	0.64	68	-0.76	74	142
HIF1A/ARNT/Cbp/p300	-0.04	0.39	0.6	35	-0.7	80	115
EPO	0.02	0.31	0.56	50	-0.61	37	87
CREBBP	0.078	0.18	0.36	100	-0.27	29	129
HIF1A/ARNT/Cbp/p300/HDAC7	-0.044	0.38	0.56	35	-0.68	80	115
PFKFB3	0.006	0.46	0.65	76	-0.77	84	160
NT5E	-0.03	0.44	0.64	59	-0.74	94	153

×

FOXM1 transcription factor network

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
NFATC3	-0.089	0.66	1	34	-1.2	103	137
PLK1	0.062	0.16	0.61	19	-0.71	7	26
BIRC5	-0.065	0.44	0.7	13	-1.2	59	72
HSPA1B	-0.09	0.66	0.94	39	-1.2	103	142
MAP2K1	0.046	0.1	0.25	56	-10000	0	56
BRCA2	-0.087	0.66	1	34	-1.2	103	137
FOXM1	-0.24	0.99	1.2	35	-1.9	103	138
XRCC1	-0.086	0.67	1	35	-1.2	98	133
FOXM1B/p19	-0.32	0.57	-10000	0	-1.4	101	101
Cyclin D1/CDK4	-0.11	0.6	0.87	29	-1.1	105	134
CDC2	-0.11	0.74	1.1	37	-1.3	106	143
TGFA	-0.072	0.58	0.86	41	-1	102	143
SKP2	-0.09	0.66	1	33	-1.2	98	131
CCNE1	0.024	0.037	0.1	21	-0.034	114	135
CKS1B	-0.096	0.69	1	35	-1.2	103	138
RB1	-0.073	0.37	0.5	16	-1	49	65
FOXM1C/SP1	-0.17	0.76	0.89	29	-1.5	104	133
AURKB	0.059	0.16	0.64	16	-0.95	4	20
CENPF	-0.11	0.71	1.1	35	-1.2	112	147
CDK4	0.025	0.052	0.15	31	-10000	0	31
MYC	-0.11	0.57	0.81	36	-1	108	144
CHEK2	0.037	0.094	0.23	51	-10000	0	51
ONECUT1	-0.091	0.64	0.9	40	-1.2	104	144
CDKN2A	0.003	0.018	-10000	0	-0.14	4	4
LAMA4	-0.094	0.66	0.98	36	-1.2	105	141
FOXM1B/HNF6	-0.17	0.78	0.94	36	-1.5	104	140
FOS	-0.15	0.7	0.99	33	-1.2	132	165
SP1	0.034	0.019	0.07	5	-0.028	39	44
CDC25B	-0.086	0.69	1	38	-1.2	106	144
response to radiation	0.024	0.068	0.15	73	-10000	0	73
CENPB	-0.077	0.68	1	39	-1.2	99	138
CENPA	-0.091	0.67	1	35	-1.2	99	134
NEK2	-0.081	0.67	1.1	34	-1.2	101	135
HIST1H2BA	-0.09	0.66	0.94	39	-1.2	103	142
CCNA2	0.022	0.031	0.094	5	-0.034	77	82
EP300	0.033	0.011	-10000	0	0	50	50
CCNB1/CDK1	-0.19	0.85	1.1	29	-1.6	111	140
CCNB2	-0.11	0.7	1	38	-1.3	108	146
CCNB1	-0.12	0.75	1.1	36	-1.3	110	146
ETV5	-0.12	0.69	1	34	-1.2	122	156
ESR1	-0.092	0.66	1	32	-1.2	99	131
CCND1	-0.097	0.62	0.9	39	-1.1	105	144
GSK3A	0.037	0.085	0.21	49	-10000	0	49
Cyclin A-E1/CDK1-2	0.048	0.1	0.26	24	-0.16	43	67
CDK2	0.024	0.037	0.1	17	-0.034	118	135
G2/M transition of mitotic cell cycle	0.028	0.083	0.18	74	-10000	0	74
FOXM1B/Cbp/p300	-0.17	0.69	0.8	19	-1.4	103	122
GAS1	-0.093	0.68	1	36	-1.2	107	143
MMP2	-0.12	0.7	1	37	-1.2	115	152
RB1/FOXM1C	-0.14	0.62	0.86	25	-1.2	103	128
CREBBP	0.036	0.005	-10000	0	0	9	9

×

Angiopoietin receptor Tie2-mediated signaling

Figure S3. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S3. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.23	0.41	-10000	0	-0.82	141	141
NCK1/PAK1/Dok-R	-0.12	0.17	-10000	0	-0.38	131	131
NCK1/Dok-R	-0.14	0.35	-10000	0	-0.86	96	96
PIK3CA	0.031	0.014	-10000	0	0	82	82
mol:beta2-estradiol	0.031	0.098	0.23	96	-10000	0	96
RELA	0.036	0.004	-10000	0	0	7	7
SHC1	0.032	0.011	-10000	0	0	52	52
Rac/GDP	0.017	0.02	-10000	0	-0.13	5	5
F2	0.053	0.11	0.28	87	-0.091	64	151
TNIP2	0.036	0.006	-10000	0	0	12	12
NF kappa B/RelA	-0.11	0.36	-10000	0	-0.83	96	96
FN1	0.035	0.009	-10000	0	0	30	30
PLD2	-0.15	0.36	-10000	0	-0.89	96	96
PTPN11	0.036	0.005	-10000	0	0	11	11
GRB14	0.032	0.013	-10000	0	0	70	70
ELK1	-0.14	0.33	-10000	0	-0.82	96	96
GRB7	0.036	0.006	-10000	0	0	15	15
PAK1	0.036	0.006	-10000	0	0	16	16
Tie2/Ang1/alpha5/beta1 Integrin	-0.13	0.36	-10000	0	-0.86	96	96
CDKN1A	-0.19	0.36	-10000	0	-0.66	166	166
ITGA5	0.033	0.012	-10000	0	0	58	58
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.14	0.36	-10000	0	-0.86	96	96
CRK	0.035	0.008	-10000	0	0	23	23
mol:NO	-0.12	0.32	0.38	3	-0.59	138	141
PLG	-0.15	0.36	-10000	0	-0.89	96	96
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.17	0.36	-10000	0	-0.75	124	124
GRB2	0.035	0.007	-10000	0	0	18	18
PIK3R1	0.032	0.012	-10000	0	0	63	63
ANGPT2	-0.22	0.45	-10000	0	-1	109	109
BMX	-0.15	0.36	-10000	0	-0.89	96	96
ANGPT1	-0.16	0.42	-10000	0	-1	95	95
tube development	-0.21	0.36	-10000	0	-0.7	165	165
ANGPT4	0.022	0.029	-10000	0	-0.025	128	128
response to hypoxia	-0.013	0.026	-10000	0	-0.063	96	96
Tie2/Ang1/GRB14	-0.14	0.37	-10000	0	-0.9	96	96
alpha5/beta1 Integrin	0.028	0.043	-10000	0	-0.14	21	21
FGF2	0.034	0.017	-10000	0	-0.014	49	49
STAT5A (dimer)	-0.24	0.44	-10000	0	-0.81	176	176
mol:L-citrulline	-0.12	0.32	0.38	3	-0.59	138	141
AGTR1	0.022	0.034	-10000	0	-0.048	92	92
MAPK14	-0.16	0.37	-10000	0	-0.9	96	96
Tie2/SHP2	-0.079	0.24	-10000	0	-0.84	32	32
TEK	-0.085	0.25	-10000	0	-0.96	29	29
RPS6KB1	-0.2	0.37	-10000	0	-0.77	136	136
Angiotensin II/AT1	0.014	0.036	0.085	1	-0.057	88	89
Tie2/Ang1/GRB2	-0.14	0.37	-10000	0	-0.9	96	96
MAPK3	-0.15	0.34	-10000	0	-0.84	96	96
MAPK1	-0.15	0.34	-10000	0	-0.84	96	96
Tie2/Ang1/GRB7	-0.14	0.38	-10000	0	-0.91	96	96
NFKB1	0.035	0.007	-10000	0	0	18	18
MAPK8	-0.15	0.36	-10000	0	-0.88	96	96
PI3K	-0.24	0.44	-10000	0	-0.9	136	136
FES	-0.16	0.37	-10000	0	-0.9	97	97
Crk/Dok-R	-0.14	0.36	-10000	0	-0.86	96	96
Tie2/Ang1/ABIN2	-0.14	0.38	-10000	0	-0.9	96	96
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.2	0.36	-10000	0	-0.73	144	144
STAT5A	0.036	0.004	-10000	0	0	5	5
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.2	0.37	-10000	0	-0.77	136	136
Tie2/Ang2	-0.29	0.5	-10000	0	-0.97	163	163
Tie2/Ang1	-0.15	0.38	-10000	0	-0.93	96	96
FOXO1	-0.22	0.39	-10000	0	-0.74	168	168
ELF1	0.028	0.036	0.11	4	-0.046	81	85
ELF2	-0.14	0.35	-10000	0	-0.87	96	96
mol:Choline	-0.15	0.35	-10000	0	-0.86	96	96
cell migration	-0.066	0.097	-10000	0	-0.21	137	137
FYN	-0.24	0.41	-10000	0	-0.81	164	164
DOK2	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.17	0.32	0.39	3	-0.59	170	173
ETS1	-0.002	0.12	-10000	0	-0.25	93	93
PXN	-0.17	0.31	-10000	0	-0.65	134	134
ITGB1	0.026	0.017	-10000	0	0	144	144
NOS3	-0.15	0.35	0.4	1	-0.67	137	138
RAC1	0.025	0.017	-10000	0	0	163	163
TNF	-0.003	0.12	-10000	0	-0.25	92	92
MAPKKK cascade	-0.15	0.35	-10000	0	-0.86	96	96
RASA1	0.035	0.009	-10000	0	0	30	30
Tie2/Ang1/Shc	-0.15	0.37	-10000	0	-0.91	96	96
NCK1	0.035	0.008	-10000	0	0	27	27
vasculogenesis	-0.1	0.29	0.36	4	-0.52	147	151
mol:Phosphatidic acid	-0.15	0.35	-10000	0	-0.86	96	96
mol:Angiotensin II	-0.004	0.013	0.023	2	-0.032	75	77
mol:NADP	-0.12	0.32	0.38	3	-0.59	138	141
Rac1/GTP	-0.18	0.34	-10000	0	-0.7	132	132
MMP2	-0.15	0.36	-10000	0	-0.9	96	96

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.022	0.15	0.21	78	-0.27	88	166
PTK2B	0.036	0.006	-10000	0	0	16	16
mol:Ca2+	-0.1	0.25	0.39	2	-0.53	74	76
EDN1	0.004	0.093	0.15	7	-0.16	100	107
EDN3	0.033	0.011	-10000	0	0	52	52
EDN2	0.036	0.006	-10000	0	0	12	12
HRAS/GDP	-0.014	0.17	0.31	16	-0.38	55	71
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.003	0.12	0.2	18	-0.26	55	73
ADCY4	-0.036	0.099	0.14	40	-0.2	98	138
ADCY5	-0.036	0.099	0.14	40	-0.2	98	138
ADCY6	-0.009	0.13	0.19	94	-0.24	63	157
ADCY7	-0.015	0.13	0.19	84	-0.24	68	152
ADCY1	-0.001	0.11	0.18	70	-0.25	40	110
ADCY2	-0.008	0.13	0.19	93	-0.24	65	158
ADCY3	-0.036	0.099	0.14	40	-0.2	98	138
ADCY8	-0.012	0.13	0.19	86	-0.24	57	143
ADCY9	-0.011	0.13	0.19	92	-0.24	66	158
arachidonic acid secretion	-0.079	0.26	0.32	28	-0.5	107	135
ETB receptor/Endothelin-1/Gq/GTP	-0.006	0.11	0.18	13	-0.26	46	59
GNAO1	0.03	0.014	-10000	0	0	87	87
HRAS	0.034	0.01	-10000	0	0	36	36
ETA receptor/Endothelin-1/G12/GTP	0.004	0.12	-10000	0	-0.23	71	71
ETA receptor/Endothelin-1/Gs/GTP	0.004	0.12	-10000	0	-0.21	104	104
mol:GTP	0	0.007	0.026	3	-0.025	4	7
COL3A1	-0.077	0.16	0.19	9	-0.37	102	111
EDNRB	0.023	0.045	0.098	61	-0.084	47	108
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.018	0.14	0.21	76	-0.29	64	140
CYSLTR1	-0.036	0.12	0.19	42	-0.25	96	138
SLC9A1	-0.014	0.087	0.13	28	-0.18	69	97
mol:GDP	-0.022	0.17	0.3	20	-0.39	54	74
SLC9A3	-0.12	0.28	-10000	0	-0.65	80	80
RAF1	-0.034	0.2	0.29	31	-0.41	84	115
JUN	-0.14	0.33	0.48	1	-0.71	88	89
JAK2	-0.022	0.14	0.21	68	-0.26	86	154
mol:IP3	-0.001	0.12	0.23	16	-0.28	41	57
ETA receptor/Endothelin-1	-0.022	0.15	-10000	0	-0.28	108	108
PLCB1	0.032	0.014	-10000	0	-0.004	58	58
PLCB2	0.029	0.023	-10000	0	-0.023	78	78
ETA receptor/Endothelin-3	0.006	0.09	-10000	0	-0.15	105	105
FOS	-0.094	0.35	0.36	31	-0.82	85	116
Gai/GDP	-0.069	0.27	-10000	0	-0.73	67	67
CRK	0.035	0.008	-10000	0	0	23	23
mol:Ca ++	-0.018	0.18	0.26	57	-0.34	75	132
BCAR1	0	0	-10000	0	-10000	0	0
PRKCB1	-0.001	0.13	0.24	23	-0.3	40	63
GNAQ	0.027	0.026	-10000	0	-0.034	70	70
GNAZ	0.031	0.013	-10000	0	0	80	80
GNAL	0.036	0.006	-10000	0	0	13	13
Gs family/GDP	-0.011	0.16	0.28	19	-0.36	54	73
ETA receptor/Endothelin-1/Gq/GTP	-0.005	0.13	0.2	14	-0.28	56	70
MAPK14	-0.011	0.1	0.17	9	-0.25	46	55
TRPC6	-0.11	0.25	0.4	1	-0.56	72	73
GNAI2	0.034	0.01	-10000	0	0	44	44
GNAI3	0.036	0.006	-10000	0	0	14	14
GNAI1	0.018	0.018	-10000	0	0	262	262
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.002	0.1	0.18	19	-0.25	48	67
ETB receptor/Endothelin-2	0.017	0.071	-10000	0	-0.11	101	101
ETB receptor/Endothelin-3	0.015	0.07	-10000	0	-0.11	95	95
ETB receptor/Endothelin-1	-0.001	0.1	0.18	26	-0.17	103	129
MAPK3	-0.076	0.32	0.35	29	-0.72	85	114
MAPK1	-0.09	0.34	0.35	30	-0.76	88	118
Rac1/GDP	-0.009	0.15	0.3	16	-0.38	38	54
cAMP biosynthetic process	0.018	0.12	0.21	65	-0.22	46	111
MAPK8	-0.14	0.3	0.35	3	-0.56	139	142
SRC	0.034	0.009	-10000	0	0	34	34
ETB receptor/Endothelin-1/Gi/GTP	-0.03	0.14	0.16	5	-0.35	57	62
p130Cas/CRK/Src/PYK2	-0.019	0.18	0.35	13	-0.48	43	56
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.013	0.15	0.31	13	-0.38	42	55
COL1A2	-0.051	0.17	0.22	2	-0.48	59	61
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.005	0.093	-10000	0	-0.15	117	117
mol:DAG	-0.001	0.12	0.23	16	-0.28	41	57
MAP2K2	-0.052	0.26	0.33	37	-0.55	85	122
MAP2K1	-0.063	0.26	0.31	31	-0.57	88	119
EDNRA	-0.011	0.11	0.15	2	-0.2	104	106
positive regulation of muscle contraction	0.027	0.15	0.22	147	-0.28	41	188
Gq family/GDP	0.006	0.16	0.31	5	-0.36	52	57
HRAS/GTP	-0.014	0.16	0.28	24	-0.35	58	82
PRKCH	-0.006	0.12	0.24	18	-0.3	39	57
RAC1	0.025	0.017	-10000	0	0	163	163
PRKCA	-0.009	0.12	0.22	19	-0.3	43	62
PRKCB	-0.003	0.12	0.22	19	-0.29	45	64
PRKCE	-0.01	0.12	0.21	18	-0.3	45	63
PRKCD	-0.004	0.13	0.26	24	-0.29	43	67
PRKCG	-0.011	0.12	0.22	18	-0.3	47	65
regulation of vascular smooth muscle contraction	-0.12	0.42	0.41	20	-1	84	104
PRKCQ	-0.003	0.11	0.25	20	-0.3	32	52
PLA2G4A	-0.089	0.28	0.33	27	-0.54	107	134
GNA14	0.027	0.026	-10000	0	-0.034	70	70
GNA15	0.03	0.019	-10000	0	-0.035	24	24
GNA12	0.023	0.018	-10000	0	0	189	189
GNA11	0.032	0.017	-10000	0	-0.036	16	16
Rac1/GTP	0.007	0.12	-10000	0	-0.23	65	65
MMP1	0.02	0.075	0.19	32	-10000	0	32

×

PDGFR-alpha signaling pathway

Figure S5. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S5. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.017	0.032	0.082	4	-0.014	219	223
PDGF/PDGFRA/CRKL	0.007	0.069	-10000	0	-0.12	95	95
positive regulation of JUN kinase activity	0.024	0.063	-10000	0	-0.12	69	69
CRKL	0.035	0.008	-10000	0	0	28	28
PDGF/PDGFRA/Caveolin-3	0.009	0.069	-10000	0	-0.11	107	107
AP1	-0.079	0.24	0.3	12	-0.59	77	89
mol:IP3	-0.015	0.047	0.093	27	-0.1	55	82
PLCG1	-0.015	0.047	0.095	26	-0.1	55	81
PDGF/PDGFRA/alphaV Integrin	0.003	0.077	-10000	0	-0.16	78	78
RAPGEF1	0.035	0.007	-10000	0	0	18	18
CRK	0.035	0.008	-10000	0	0	23	23
mol:Ca2+	-0.015	0.047	0.093	27	-0.1	55	82
CAV3	0.036	0.005	-10000	0	0	11	11
CAV1	0.016	0.018	-10000	0	0	288	288
SHC/Grb2/SOS1	0.028	0.065	-10000	0	-0.12	69	69
PDGF/PDGFRA/Shf	-0.005	0.055	-10000	0	-0.09	121	121
FOS	-0.093	0.22	0.26	5	-0.6	72	77
JUN	-0.026	0.058	0.21	10	-0.2	18	28
oligodendrocyte development	0.003	0.077	-10000	0	-0.16	78	78
GRB2	0.035	0.007	-10000	0	0	18	18
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:DAG	-0.015	0.047	0.093	27	-0.1	55	82
PDGF/PDGFRA	0.017	0.032	0.082	4	-0.014	219	223
actin cytoskeleton reorganization	0.006	0.067	-10000	0	-0.14	66	66
SRF	-0.015	0.021	0.034	56	-10000	0	56
SHC1	0.033	0.011	-10000	0	0	52	52
PI3K	0.007	0.091	-10000	0	-0.15	107	107
PDGF/PDGFRA/Crk/C3G	0.027	0.073	-10000	0	-0.13	76	76
JAK1	-0.006	0.03	0.082	33	-10000	0	33
ELK1/SRF	-0.02	0.084	0.14	67	-0.16	59	126
SHB	0.033	0.011	-10000	0	0	51	51
SHF	0	0	-10000	0	-10000	0	0
CSNK2A1	0.026	0.034	0.078	2	-0.032	101	103
GO:0007205	-0.028	0.071	0.11	25	-0.2	55	80
SOS1	0	0	-10000	0	-10000	0	0
Ras protein signal transduction	0.024	0.063	-10000	0	-0.12	69	69
PDGF/PDGFRA/SHB	0.006	0.067	-10000	0	-0.14	66	66
PDGF/PDGFRA/Caveolin-1	-0.015	0.078	-10000	0	-0.16	98	98
ITGAV	0.035	0.009	-10000	0	0	31	31
ELK1	-0.033	0.069	0.089	26	-0.15	96	122
PIK3CA	0.031	0.014	-10000	0	0	82	82
PDGF/PDGFRA/Crk	0.005	0.074	-10000	0	-0.15	77	77
JAK-STAT cascade	-0.006	0.03	0.082	33	-10000	0	33
cell proliferation	-0.005	0.055	-10000	0	-0.09	121	121

×

TCGA08_rtk_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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.025	0.017	-10000	0	0	166	166
HRAS	0.034	0.009	-10000	0	0	36	36
EGFR	0.009	0.016	-10000	0	0	379	379
AKT	0.092	0.12	0.25	128	-0.18	12	140
FOXO3	0	0	-10000	0	-10000	0	0
AKT1	0.033	0.011	-10000	0	0	54	54
FOXO1	0	0	-10000	0	-10000	0	0
AKT3	0.035	0.007	-10000	0	0	20	20
FOXO4	0	0	-10000	0	-10000	0	0
MET	0.023	0.018	-10000	0	0	190	190
PIK3CA	0.031	0.014	-10000	0	0	82	82
PIK3CB	0.036	0.007	-10000	0	0	17	17
NRAS	0.032	0.012	-10000	0	0	63	63
PIK3CG	0.025	0.017	-10000	0	0	164	164
PIK3R3	0.036	0.006	-10000	0	0	15	15
PIK3R2	0.035	0.008	-10000	0	0	26	26
NF1	0.036	0.003	-10000	0	0	4	4
RAS	-0.003	0.054	0.14	3	-0.24	11	14
ERBB2	0.036	0.004	-10000	0	0	6	6
proliferation/survival/translation	-0.027	0.052	0.22	4	-0.2	11	15
PI3K	0.041	0.093	0.22	79	-0.15	12	91
PIK3R1	0.032	0.012	-10000	0	0	63	63
KRAS	0.034	0.009	-10000	0	0	34	34
FOXO	0.095	0.093	0.2	169	-10000	0	169
AKT2	0.035	0.008	-10000	0	0	28	28
PTEN	0.025	0.017	-10000	0	0	168	168

×

TCGA08_p53

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
CDKN2A	-0.001	0.004	0	448	-10000	0	448
TP53	0.004	0.033	-10000	0	-0.22	8	8
Senescence	0.004	0.035	-10000	0	-0.22	10	10
Apoptosis	0.004	0.035	-10000	0	-0.22	10	10
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	-0.001	0.019	0.3	2	-10000	0	2
MDM4	0.034	0.01	-10000	0	0	37	37

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.034	0.01	-10000	0	0	41	41
GNB1/GNG2	-0.046	0.077	-10000	0	-0.17	133	133
AKT1	-0.003	0.16	0.27	34	-0.28	47	81
EGF	0.035	0.008	-10000	0	0	25	25
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.016	0.067	0.27	19	-0.17	3	22
mol:Ca2+	0	0.19	0.35	25	-0.27	116	141
LYN	-0.016	0.07	0.28	18	-0.17	6	24
RhoA/GTP	0	0.083	0.16	26	-0.13	89	115
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.016	0.2	0.36	27	-0.32	126	153
GNG2	0	0	-10000	0	-10000	0	0
ARRB2	0.035	0.008	-10000	0	0	25	25
TP alpha/Gq family/GDP/G beta5/gamma2	0.003	0.076	-10000	0	-0.24	32	32
G beta5/gamma2	-0.054	0.1	-10000	0	-0.23	129	129
PRKCH	-0.016	0.2	0.36	23	-0.32	127	150
DNM1	0.035	0.008	-10000	0	0	26	26
TXA2/TP beta/beta Arrestin3	0.015	0.018	-10000	0	-10000	0	0
mol:GTP	0.001	0.002	0.005	56	-0.002	4	60
PTGDR	0.035	0.008	-10000	0	0	28	28
G12 family/GTP	-0.044	0.14	-10000	0	-0.29	93	93
ADRBK1	0.036	0.005	-10000	0	0	10	10
ADRBK2	0.035	0.009	-10000	0	0	29	29
RhoA/GTP/ROCK1	0.044	0.027	-10000	0	-0.13	10	10
mol:GDP	-0.008	0.13	0.41	15	-0.27	21	36
mol:NADP	0.025	0.017	-10000	0	0	168	168
RAB11A	0.036	0.006	-10000	0	0	16	16
PRKG1	0.026	0.017	-10000	0	0	147	147
mol:IP3	-0.012	0.22	0.38	23	-0.34	124	147
cell morphogenesis	0.044	0.027	-10000	0	-0.13	10	10
PLCB2	-0.036	0.27	0.43	15	-0.45	124	139
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.014	0.069	0.27	20	-10000	0	20
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.02	0.054	0.24	10	-0.17	8	18
RHOA	0.035	0.007	-10000	0	0	21	21
PTGIR	0.035	0.009	-10000	0	0	31	31
PRKCB1	-0.017	0.22	0.37	22	-0.34	125	147
GNAQ	0.035	0.009	-10000	0	0	30	30
mol:L-citrulline	0.025	0.017	-10000	0	0	168	168
TXA2/TXA2-R family	-0.048	0.28	0.42	20	-0.47	133	153
LCK	-0.016	0.067	0.27	18	-10000	0	18
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.032	0.039	0.19	3	-0.13	1	4
TXA2-R family/G12 family/GDP/G beta/gamma	-0.02	0.14	-10000	0	-0.46	45	45
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.029	0.041	0.19	3	-0.14	2	5
MAPK14	-0.004	0.15	0.29	34	-0.22	122	156
TGM2/GTP	-0.015	0.24	0.41	22	-0.38	95	117
MAPK11	-0.006	0.15	0.29	31	-0.22	123	154
ARHGEF1	0.01	0.12	0.22	50	-0.18	89	139
GNAI2	0.034	0.01	-10000	0	0	44	44
JNK cascade	-0.021	0.22	0.38	23	-0.35	133	156
RAB11/GDP	0.034	0.009	-10000	0	-0.008	21	21
ICAM1	-0.004	0.18	0.32	34	-0.27	125	159
cAMP biosynthetic process	-0.013	0.2	0.35	23	-0.32	96	119
Gq family/GTP/EBP50	0.013	0.054	0.24	7	-0.16	31	38
actin cytoskeleton reorganization	0.044	0.027	-10000	0	-0.13	10	10
SRC	-0.02	0.055	0.24	13	-10000	0	13
GNB5	0.035	0.007	-10000	0	0	22	22
GNB1	0.035	0.007	-10000	0	0	20	20
EGF/EGFR	-0.009	0.11	0.28	21	-0.23	41	62
VCAM1	-0.023	0.21	0.32	35	-0.33	135	170
TP beta/Gq family/GDP/G beta5/gamma2	0.003	0.076	-10000	0	-0.24	32	32
platelet activation	-0.009	0.19	0.35	29	-0.28	119	148
PGI2/IP	0.026	0.007	-10000	0	-10000	0	0
PRKACA	0.014	0.024	-10000	0	-10000	0	0
Gq family/GDP/G beta5/gamma2	0.006	0.067	-10000	0	-0.21	30	30
TXA2/TP beta/beta Arrestin2	0.004	0.049	-10000	0	-0.26	12	12
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.006	0.02	-10000	0	-10000	0	0
mol:DAG	-0.021	0.24	0.39	22	-0.38	128	150
EGFR	0.009	0.016	-10000	0	0	379	379
TXA2/TP alpha	-0.028	0.26	0.43	16	-0.43	97	113
Gq family/GTP	0.009	0.047	0.2	10	-0.13	28	38
YES1	-0.015	0.07	0.27	19	-0.17	3	22
GNAI2/GTP	0.007	0.048	-10000	0	-0.13	2	2
PGD2/DP	0.026	0.006	-10000	0	-10000	0	0
SLC9A3R1	0.034	0.009	-10000	0	0	36	36
FYN	-0.017	0.07	0.27	18	-0.17	7	25
mol:NO	0.025	0.017	-10000	0	0	168	168
GNA15	0.033	0.011	-10000	0	0	51	51
PGK/cGMP	0.027	0.025	-10000	0	-10000	0	0
RhoA/GDP	0.034	0.01	-10000	0	-0.006	26	26
TP alpha/TGM2/GDP/G beta/gamma	0.029	0.042	0.18	2	-0.13	1	3
NOS3	0.025	0.017	-10000	0	0	168	168
RAC1	0.025	0.017	-10000	0	0	163	163
PRKCA	-0.014	0.2	0.36	23	-0.32	126	149
PRKCB	-0.015	0.21	0.36	23	-0.32	130	153
PRKCE	-0.017	0.21	0.36	23	-0.33	126	149
PRKCD	-0.019	0.22	0.36	28	-0.35	128	156
PRKCG	-0.022	0.22	0.37	22	-0.35	132	154
muscle contraction	-0.041	0.26	0.41	20	-0.44	134	154
PRKCZ	-0.016	0.2	0.36	24	-0.31	133	157
ARR3	0.037	0	-10000	0	-10000	0	0
TXA2/TP beta	0.036	0.038	0.19	2	-0.14	1	3
PRKCQ	-0.026	0.2	0.36	23	-0.32	122	145
MAPKKK cascade	-0.031	0.24	0.39	21	-0.4	125	146
SELE	-0.01	0.18	0.33	27	-0.27	133	160
TP beta/GNAI2/GDP/G beta/gamma	0.025	0.053	0.19	2	-0.16	14	16
ROCK1	0.036	0.006	-10000	0	0	15	15
GNA14	0.035	0.009	-10000	0	0	29	29
chemotaxis	-0.068	0.32	0.46	15	-0.56	135	150
GNA12	0.023	0.018	-10000	0	0	189	189
GNA13	0.035	0.007	-10000	0	0	20	20
GNA11	0.033	0.011	-10000	0	0	51	51
Rac1/GTP	0.017	0.02	-10000	0	-0.14	5	5

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.02	0.17	-10000	0	-0.66	31	31
oxygen homeostasis	0.004	0.021	0.045	65	-0.024	27	92
TCEB2	0.036	0.004	-10000	0	0	7	7
TCEB1	0.035	0.007	-10000	0	0	22	22
VHL/Elongin B/Elongin C/HIF2A	0.002	0.14	0.3	23	-0.23	55	78
EPO	-0.043	0.2	0.4	17	-0.42	63	80
FIH (dimer)	0.015	0.039	0.11	17	-0.04	58	75
APEX1	0.016	0.043	0.11	8	-0.049	46	54
SERPINE1	-0.078	0.2	0.38	2	-0.46	83	85
FLT1	-0.012	0.16	-10000	0	-0.64	27	27
ADORA2A	-0.038	0.24	0.44	35	-0.42	77	112
germ cell development	-0.038	0.23	0.43	33	-0.41	80	113
SLC11A2	-0.036	0.25	0.46	34	-0.43	77	111
BHLHE40	-0.041	0.24	0.44	32	-0.42	81	113
HIF1AN	0.015	0.039	0.11	17	-0.04	58	75
HIF2A/ARNT/SIRT1	-0.018	0.17	0.35	25	-0.29	62	87
ETS1	0.047	0.033	0.12	43	-0.11	11	54
CITED2	-0.055	0.26	-10000	0	-0.81	49	49
KDR	-0.002	0.16	-10000	0	-0.83	16	16
PGK1	-0.041	0.26	0.46	34	-0.45	81	115
SIRT1	0.024	0.017	-10000	0	0	174	174
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	-0.03	0.27	0.48	12	-0.48	78	90
EPAS1	0	0.13	0.31	35	-0.26	41	76
SP1	0.04	0.011	0.11	8	-10000	0	8
ABCG2	-0.047	0.26	0.43	40	-0.44	93	133
EFNA1	-0.042	0.24	0.44	30	-0.45	74	104
FXN	-0.041	0.24	0.44	35	-0.42	75	110
POU5F1	-0.041	0.24	0.44	32	-0.42	81	113
neuron apoptosis	0.03	0.26	0.47	78	-0.47	13	91
EP300	0.033	0.011	-10000	0	0	50	50
EGLN3	0.018	0.04	0.11	15	-0.04	62	77
EGLN2	0.022	0.042	0.11	19	-0.039	61	80
EGLN1	0.022	0.042	0.11	19	-0.04	62	81
VHL/Elongin B/Elongin C	0.045	0.024	-10000	0	-0.12	9	9
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.016	0.043	0.11	7	-0.05	42	49
SLC2A1	-0.053	0.24	0.45	26	-0.45	74	100
TWIST1	-0.062	0.21	0.42	15	-0.43	87	102
ELK1	0.038	0.036	0.12	29	-0.095	25	54
HIF2A/ARNT/Cbp/p300	-0.001	0.19	0.38	31	-0.31	58	89
VEGFA	-0.041	0.24	0.44	32	-0.42	81	113
CREBBP	0.036	0.005	-10000	0	0	9	9

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	0.034	0.01	-9999	0	39	39
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.036	0.004	-9999	0	7	7
TCEB1	0.035	0.007	-9999	0	22	22
HIF1A/p53	-0.063	0.14	-9999	-0.27	141	141
HIF1A	-0.059	0.12	-9999	-0.28	122	122
COPS5	0.036	0.006	-9999	0	14	14
VHL/Elongin B/Elongin C/RBX1/CUL2	0.046	0.06	-9999	-0.13	22	22
FIH (dimer)	0.025	0.017	-9999	0	156	156
CDKN2A	0.004	0.012	-9999	0	448	448
ARNT/IPAS	0.05	0.015	-9999	-10000	0	0
HIF1AN	0.025	0.017	-9999	0	156	156
GNB2L1	0.037	0.002	-9999	0	2	2
HIF1A/ARNT	-0.062	0.14	-9999	-0.28	141	141
CUL2	0.025	0.017	-9999	0	158	158
OS9	0.031	0.013	-9999	0	73	73
RACK1/Elongin B/Elongin C	0.068	0.032	-9999	-0.14	10	10
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.075	0.13	-9999	-0.27	143	143
PHD1-3/OS9	0.062	0.065	-9999	-0.14	30	30
HIF1A/RACK1/Elongin B/Elongin C	-0.043	0.15	-9999	-0.27	140	140
VHL	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
HIF1A/JAB1	-0.063	0.14	-9999	-0.28	144	144
EGLN3	0.03	0.014	-9999	0	93	93
EGLN2	0.035	0.009	-9999	0	29	29
EGLN1	0.034	0.009	-9999	0	34	34
TP53	0.031	0.013	-9999	0	73	73
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.005	0.1	-9999	-0.61	12	12
ARNT	0.036	0.004	-9999	0	6	6
ARD1A	0.036	0.003	-9999	0	4	4
RBX1	0.033	0.011	-9999	0	47	47
HIF1A/p19ARF	-0.065	0.12	-9999	-0.26	120	120

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.034	0.009	-10000	0	0	36	36
EGFR	0.009	0.016	-10000	0	0	379	379
EGF/EGFR	0.001	0.054	-10000	0	-0.11	65	65
EGF/EGFR dimer/SHC/GRB2/SOS1	0.006	0.058	-10000	0	-0.12	61	61
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	0.028	0.016	-10000	0	0	123	123
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	0.035	0.008	-10000	0	0	25	25
EGF/EGFR dimer/SHC	0	0.056	-10000	0	-0.13	61	61
mol:GDP	0.004	0.056	-10000	0	-0.12	61	61
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0.033	0.011	-10000	0	0	52	52
GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
HRAS/GTP	-0.004	0.052	-10000	0	-0.12	69	69
SHC1	0.033	0.011	-10000	0	0	52	52
HRAS/GDP	0	0.059	-10000	0	-0.12	69	69
FRAP1	0.092	0.12	0.18	302	-0.19	4	306
EGF/EGFR dimer	-0.005	0.058	-10000	0	-0.14	64	64
SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.035	0.007	-10000	0	0	18	18
ETA receptor/Endothelin-1	0.023	0.06	-10000	0	-0.14	51	51

×

Effects of Botulinum toxin

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
STX1A	-0.007	0.006	0	180	-10000	0	180
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.04	0.04	-10000	0	-0.14	18	18
STXBP1	0.029	0.015	-10000	0	0	107	107
ACh/CHRNA1	0.028	0.055	0.097	53	-0.075	91	144
RAB3GAP2/RIMS1/UNC13B	0.053	0.05	-10000	0	-0.13	23	23
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.035	0.007	-10000	0	0	21	21
mol:ACh	0.019	0.066	0.097	152	-0.09	87	239
RAB3GAP2	0.035	0.009	-10000	0	0	29	29
STX1A/SNAP25/VAMP2	0.026	0.1	0.18	18	-0.15	79	97
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.028	0.054	0.097	53	-0.075	91	144
UNC13B	0.032	0.013	-10000	0	0	68	68
CHRNA1	0.035	0.007	-10000	0	0	18	18
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0.014	0.043	0.1	22	-0.086	40	62
SNAP25	0.002	0.003	-10000	0	0	274	274
VAMP2	0.004	0.001	-10000	0	0	49	49
SYT1	0.018	0.018	-10000	0	0	264	264
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.017	0.016	0.089	1	-10000	0	1
STX1A/SNAP25 fragment 1/VAMP2	0.026	0.1	0.18	18	-0.15	79	97

×

Canonical Wnt signaling pathway

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
HDAC1	0.033	0.046	0.12	72	-0.039	84	156
AES	0.032	0.042	0.11	66	-0.036	80	146
FBXW11	0.035	0.007	-10000	0	0	22	22
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.033	0.027	-10000	0	-10000	0	0
SMAD4	0.032	0.012	-10000	0	0	59	59
DKK2	0.035	0.009	-10000	0	0	31	31
TLE1	0.032	0.042	0.11	70	-0.036	85	155
MACF1	0.034	0.011	-10000	0	0	49	49
CTNNB1	0.048	0.11	0.25	28	-0.35	14	42
WIF1	0.028	0.015	-10000	0	0	112	112
beta catenin/RanBP3	0.074	0.16	0.41	66	-0.35	8	74
KREMEN2	0.036	0.005	-10000	0	0	9	9
DKK1	0.017	0.018	-10000	0	0	277	277
beta catenin/beta TrCP1	0.062	0.11	0.26	27	-0.33	16	43
FZD1	0.024	0.017	-10000	0	0	175	175
AXIN2	-0.024	0.094	0.1	9	-0.23	69	78
AXIN1	0.038	0.001	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	0	10	10
Axin1/APC/GSK3/beta catenin	0.017	0.16	-10000	0	-0.6	29	29
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.024	0.13	0.24	13	-0.42	20	33
Axin1/APC/GSK3	0.005	0.087	0.24	4	-0.38	16	20
Axin1/APC/GSK3/beta catenin/Macf1	0.034	0.14	0.27	10	-0.4	27	37
HNF1A	0.007	0.03	0.071	78	-0.03	11	89
CTBP1	0.031	0.042	0.11	63	-0.037	84	147
MYC	-0.1	0.41	0.73	14	-1.3	51	65
RANBP3	0.035	0.008	-10000	0	0	22	22
DKK2/LRP6/Kremen 2	0.064	0.027	-10000	0	-0.13	1	1
NKD1	0	0.001	-10000	0	-10000	0	0
TCF4	0.03	0.039	0.11	60	-0.036	68	128
TCF3	0.033	0.043	0.11	71	-0.036	82	153
WNT1/LRP6/FZD1/Axin1	0.06	0.046	-10000	0	-10000	0	0
Ran/GTP	0.026	0.016	-10000	0	-0.13	5	5
CtBP/CBP/TCF/TLE1/AES	0.037	0.19	0.46	68	-0.32	26	94
LEF1	0.034	0.044	0.11	74	-0.037	86	160
DVL1	0.01	0.096	-10000	0	-0.42	17	17
CSNK2A1	0.033	0.011	-10000	0	0	51	51
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.009	0.16	0.25	11	-0.48	33	44
DKK1/LRP6/Kremen 2	0.03	0.037	-10000	0	-10000	0	0
LRP6	0.034	0.01	-10000	0	0	40	40
CSNK1A1	0.035	0.047	0.12	73	-0.039	86	159
NLK	0.027	0.023	-10000	0	-0.032	57	57
CCND1	-0.083	0.36	0.89	2	-1.3	39	41
WNT1	0.036	0.007	-10000	0	0	18	18
GSK3A	0.035	0.009	-10000	0	0	28	28
GSK3B	0.034	0.01	-10000	0	0	39	39
FRAT1	0.025	0.017	-10000	0	0	163	163
PPP2R5D	0.025	0.042	-10000	0	-0.24	6	6
APC	0.041	0.1	0.18	163	-10000	0	163
WNT1/LRP6/FZD1	0.001	0.047	-10000	0	-0.23	12	12
CREBBP	0.034	0.043	0.11	73	-0.036	86	159

×

Syndecan-3-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.036	0.006	-9999	0	13	13
Syndecan-3/Src/Cortactin	-0.027	0.19	-9999	-0.45	74	74
Syndecan-3/Neurocan	-0.066	0.18	-9999	-0.48	79	79
POMC	0.036	0.006	-9999	0	13	13
EGFR	0.009	0.016	-9999	0	379	379
Syndecan-3/EGFR	-0.058	0.16	-9999	-0.42	78	78
AGRP	0.036	0.005	-9999	0	8	8
NCSTN	0.035	0.009	-9999	0	29	29
PSENEN	0.035	0.009	-9999	0	31	31
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.036	0.006	-9999	0	14	14
APH1A	0.036	0.006	-9999	0	12	12
NCAN	0	0	-9999	-10000	0	0
long-term memory	-0.034	0.2	-9999	-0.5	79	79
Syndecan-3/IL8	-0.057	0.18	-9999	-0.48	79	79
PSEN1	0.033	0.011	-9999	0	47	47
Src/Cortactin	0.049	0.018	-9999	-0.14	1	1
FYN	0.03	0.014	-9999	0	88	88
limb bud formation	-0.067	0.18	-9999	-0.5	79	79
MC4R	0.035	0.007	-9999	0	21	21
SRC	0.034	0.009	-9999	0	34	34
PTN	0.022	0.018	-9999	0	207	207
FGFR/FGF/Syndecan-3	-0.067	0.19	-9999	-0.5	79	79
neuron projection morphogenesis	-0.072	0.16	-9999	-0.44	74	74
Syndecan-3/AgRP	-0.044	0.19	-9999	-0.49	79	79
Syndecan-3/AgRP/MC4R	-0.025	0.2	-9999	-0.48	78	78
Fyn/Cortactin	0.029	0.062	-9999	-0.15	53	53
SDC3	-0.068	0.19	-9999	-0.51	79	79
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.056	0.18	-9999	-0.47	79	79
IL8	0.019	0.018	-9999	0	244	244
Syndecan-3/Fyn/Cortactin	-0.034	0.21	-9999	-0.51	79	79
Syndecan-3/CASK	-0.066	0.18	-9999	-0.48	79	79
alpha-MSH/MC4R	0.051	0.014	-9999	-10000	0	0
Gamma Secretase	0.08	0.072	-9999	-0.16	28	28

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.006	0.089	-9999	-0.17	89	89
FZD6	0.027	0.016	-9999	0	130	130
WNT6	0.037	0.002	-9999	0	1	1
WNT4	0.035	0.007	-9999	0	20	20
FZD3	0.029	0.015	-9999	0	109	109
WNT5A	0.03	0.015	-9999	0	99	99
WNT11	0.036	0.006	-9999	0	15	15

×

Arf6 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
CENTA1/KIF3B	0.014	0.035	-10000	0	-0.11	38	38
ARNO/beta Arrestin1-2	0.042	0.025	-10000	0	-0.095	7	7
EGFR	0.009	0.016	-10000	0	0	379	379
EPHA2	0.033	0.011	-10000	0	0	55	55
USP6	0.035	0.007	-10000	0	0	18	18
IQSEC1	0.036	0.007	-10000	0	0	19	19
EGFR/EGFR/EGF/EGF	-0.005	0.058	-10000	0	-0.14	64	64
ARRB2	0.012	0.025	-10000	0	-0.2	7	7
mol:GTP	0.002	0.011	0.049	1	-0.063	2	3
ARRB1	0.036	0.005	-10000	0	0	11	11
FBXO8	0	0	-10000	0	-10000	0	0
TSHR	0.033	0.011	-10000	0	0	51	51
EGF	0.035	0.008	-10000	0	0	25	25
somatostatin receptor activity	0	0	0.001	152	0	6	158
ARAP2	0	0	0	130	0	3	133
mol:GDP	0.068	0.068	0.16	125	-0.16	4	129
mol:PI-3-4-5-P3	0	0	0	128	0	5	133
ITGA2B	0.037	0.003	-10000	0	0	3	3
ARF6	0.035	0.009	-10000	0	0	29	29
Ephrin A1/EPHA2/NCK1/GIT1	0.075	0.055	-10000	0	-0.13	25	25
ADAP1	0	0	0	70	0	1	71
KIF13B	0.032	0.012	-10000	0	0	63	63
HGF/MET	0.032	0.027	-10000	0	-10000	0	0
PXN	0.036	0.004	-10000	0	0	7	7
ARF6/GTP	0.084	0.088	0.19	129	-0.2	5	134
EGFR/EGFR/EGF/EGF/ARFGEP100	0.001	0.056	-10000	0	-0.13	62	62
ADRB2	0.034	0.01	-10000	0	0	40	40
receptor agonist activity	0	0	0	135	0	4	139
actin filament binding	0	0	0	140	0	6	146
SRC	0.034	0.009	-10000	0	0	34	34
ITGB3	0.037	0.003	-10000	0	0	4	4
GNAQ	0.035	0.009	-10000	0	0	30	30
EFA6/PI-4-5-P2	0.001	0.001	0.001	169	-0.001	4	173
ARF6/GDP	0.035	0.062	0.16	14	-0.19	16	30
ARF6/GDP/GULP/ACAP1	0.055	0.074	0.21	17	-0.17	2	19
alphaIIb/beta3 Integrin/paxillin/GIT1	0.093	0.01	-10000	0	-10000	0	0
ACAP1	0	0	0	63	-10000	0	63
ACAP2	0	0	0	106	0	3	109
LHCGR/beta Arrestin2	0.03	0.024	-10000	0	-0.14	7	7
EFNA1	0.033	0.011	-10000	0	0	52	52
HGF	0.024	0.018	-10000	0	0	177	177
CYTH3	0	0	0.001	142	0	5	147
CYTH2	0	0.001	0.003	1	-0.003	6	7
NCK1	0.035	0.008	-10000	0	0	27	27
fibronectin binding	0	0	0	138	0	5	143
endosomal lumen acidification	0	0	0	138	0	5	143
microtubule-based process	0	0	-10000	0	0	1	1
GULP1	0.025	0.017	-10000	0	0	168	168
GNAQ/ARNO	0.027	0.008	0.041	6	0	30	36
mol:Phosphatidic acid	0	0	0	106	0	3	109
PIP3-E	0.03	0.014	-10000	0	0	90	90
MET	0.023	0.018	-10000	0	0	190	190
GNA14	0.035	0.009	-10000	0	0	29	29
GNA15	0.033	0.011	-10000	0	0	51	51
GIT1	0.037	0.003	-10000	0	0	3	3
mol:PI-4-5-P2	0	0	0.001	149	-0.001	5	154
GNA11	0.033	0.011	-10000	0	0	51	51
LHCGR	0.037	0.002	-10000	0	0	2	2
AGTR1	0.035	0.008	-10000	0	0	22	22
desensitization of G-protein coupled receptor protein signaling pathway	0.03	0.024	-10000	0	-0.14	7	7
IPCEF1/ARNO	0.007	0.044	-10000	0	-0.093	51	51
alphaIIb/beta3 Integrin	0.054	0.005	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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
ERK1-2/ELK1	0.024	0.14	-10000	0	-0.28	54	54
MAP3K8	0.022	0.018	-10000	0	0	201	201
FOS	0.019	0.1	0.21	1	-0.32	19	20
PRKCA	0.029	0.026	-10000	0	-0.03	78	78
PTPN7	0.028	0.029	0.067	53	-0.03	90	143
HRAS	0.034	0.01	-10000	0	0	36	36
PRKCB	0	0.008	0.017	61	-0.012	79	140
NRAS	0.032	0.012	-10000	0	0	63	63
RAS family/GTP	0.043	0.067	-10000	0	-0.14	54	54
MAPK3	0.035	0.05	-10000	0	-0.3	2	2
MAP2K1	0.008	0.057	-10000	0	-0.22	13	13
ELK1	0.026	0.029	-10000	0	-0.04	81	81
BRAF	0.007	0.021	-10000	0	-10000	0	0
mol:GTP	0	0.002	0.003	61	-0.004	80	141
MAPK1	0.008	0.12	-10000	0	-0.42	34	34
RAF1	-0.001	0.068	-10000	0	-0.34	17	17
KRAS	0.034	0.009	-10000	0	0	34	34

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.006	0.058	-10000	0	-0.15	61	61
NF kappa B1 p50/RelA/I kappa B alpha	0.007	0.096	0.21	13	-0.21	39	52
AP1	-0.01	0.076	0.089	17	-0.15	93	110
mol:PIP3	-0.024	0.05	-10000	0	-0.13	77	77
AKT1	0	0.094	0.2	21	-0.23	34	55
PTK2B	-0.002	0.058	0.12	6	-0.15	58	64
RHOA	0.02	0.077	0.16	30	-0.32	12	42
PIK3CB	0.035	0.007	-10000	0	0	17	17
mol:Ca2+	-0.009	0.038	0.17	4	-0.14	19	23
MAGI3	0	0	-10000	0	-10000	0	0
RELA	0.036	0.004	-10000	0	0	7	7
apoptosis	0.002	0.063	0.1	36	-0.16	54	90
HRAS/GDP	0.021	0.028	-10000	0	-0.13	16	16
positive regulation of microtubule depolymerization	-0.021	0.074	0.17	10	-0.2	47	57
NF kappa B1 p50/RelA	-0.02	0.067	0.077	78	-0.17	54	132
endothelial cell migration	-0.018	0.099	-10000	0	-0.3	54	54
ADCY4	-0.005	0.09	0.15	13	-0.25	38	51
ADCY5	-0.005	0.09	0.15	13	-0.25	38	51
ADCY6	0.001	0.091	0.15	18	-0.24	37	55
ADCY7	-0.002	0.096	0.16	17	-0.24	43	60
ADCY1	-0.009	0.081	0.15	10	-0.25	33	43
ADCY2	-0.001	0.093	0.16	15	-0.24	40	55
ADCY3	-0.005	0.09	0.15	13	-0.25	38	51
ADCY8	-0.002	0.091	0.15	20	-0.24	39	59
ADCY9	0	0.092	0.16	18	-0.24	40	58
GSK3B	-0.009	0.065	0.18	7	-0.16	56	63
arachidonic acid secretion	-0.018	0.11	0.15	15	-0.25	65	80
GNG2	0	0.001	0.002	1	-0.003	12	13
TRIP6	-0.017	0.085	-10000	0	-0.25	57	57
GNAO1	0.003	0.058	0.12	24	-0.16	48	72
HRAS	0.034	0.009	-10000	0	0	36	36
NFKBIA	-0.017	0.084	0.18	15	-0.22	37	52
GAB1	0.033	0.011	-10000	0	0	55	55
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.006	0.21	-10000	0	-0.8	31	31
JUN	0.034	0.01	-10000	0	0	41	41
LPA/LPA2/NHERF2	0.019	0.029	-10000	0	-0.062	54	54
TIAM1	-0.013	0.25	-10000	0	-0.98	31	31
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	-0.008	0.037	0.17	3	-0.14	19	22
PLCB3	0.006	0.036	0.2	5	-0.063	52	57
FOS	0.025	0.017	-10000	0	0	162	162
positive regulation of mitosis	-0.018	0.11	0.15	15	-0.25	65	80
LPA/LPA1-2-3	-0.008	0.041	-10000	0	-0.13	54	54
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0.001	-10000	0	-0.002	1	1
BCAR1	0	0	-10000	0	-10000	0	0
stress fiber formation	0.009	0.068	-10000	0	-0.28	10	10
GNAZ	0.002	0.064	0.12	28	-0.17	49	77
EGFR/PI3K-beta/Gab1	-0.02	0.054	-10000	0	-0.13	77	77
positive regulation of dendritic cell cytokine production	-0.008	0.041	-10000	0	-0.12	54	54
LPA/LPA2/MAGI-3	-0.004	0.017	-10000	0	-0.052	54	54
ARHGEF1	0.037	0.12	0.19	150	-0.17	34	184
GNAI2	0.004	0.07	0.12	40	-0.18	54	94
GNAI3	0.006	0.064	0.12	39	-0.16	54	93
GNAI1	0.003	0.046	0.13	18	-0.16	28	46
LPA/LPA3	-0.006	0.021	-10000	0	-0.067	54	54
LPA/LPA2	-0.006	0.021	-10000	0	-0.066	54	54
LPA/LPA1	-0.012	0.055	-10000	0	-0.17	54	54
HB-EGF/EGFR	-0.012	0.059	-10000	0	-0.14	77	77
HBEGF	0.011	0.046	0.094	114	-10000	0	114
mol:DAG	-0.008	0.037	0.17	3	-0.14	19	22
cAMP biosynthetic process	0.001	0.11	0.18	37	-0.26	46	83
NFKB1	0.035	0.007	-10000	0	0	18	18
SRC	0.034	0.009	-10000	0	0	34	34
GNB1	0.035	0.007	-10000	0	0	20	20
LYN	-0.023	0.096	0.17	19	-0.22	64	83
GNAQ	0.008	0.026	0.057	38	-0.058	56	94
LPAR2	0	0.001	0.002	1	-0.003	4	5
LPAR3	0	0.001	-10000	0	-0.002	8	8
LPAR1	-0.01	0.033	-10000	0	-0.11	54	54
IL8	-0.13	0.2	0.3	13	-0.4	158	171
PTK2	0.013	0.057	0.12	38	-0.14	50	88
Rac1/GDP	0.017	0.02	-10000	0	-0.13	5	5
CASP3	0.002	0.063	0.1	36	-0.16	54	90
EGFR	0.009	0.016	-10000	0	0	379	379
PLCG1	0.005	0.038	0.077	6	-0.13	24	30
PLD2	0.015	0.054	0.12	38	-0.12	53	91
G12/G13	0.019	0.063	-10000	0	-0.15	46	46
PI3K-beta	-0.014	0.068	-10000	0	-0.22	32	32
cell migration	-0.001	0.073	-10000	0	-0.25	28	28
SLC9A3R2	0.036	0.005	-10000	0	0	8	8
PXN	0.008	0.069	-10000	0	-0.29	10	10
HRAS/GTP	-0.019	0.11	0.16	9	-0.26	62	71
RAC1	0.025	0.017	-10000	0	0	163	163
MMP9	0.017	0.018	-10000	0	0	280	280
PRKCE	0.036	0.003	-10000	0	0	3	3
PRKCD	-0.004	0.054	0.19	14	-0.2	3	17
Gi(beta/gamma)	-0.01	0.12	0.17	12	-0.27	58	70
mol:LPA	-0.01	0.033	-10000	0	-0.11	54	54
TRIP6/p130 Cas/FAK1/Paxillin	-0.009	0.08	-10000	0	-0.24	35	35
MAPKKK cascade	-0.018	0.11	0.15	15	-0.25	65	80
contractile ring contraction involved in cytokinesis	0.02	0.079	0.17	27	-0.32	13	40
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	0.008	0.026	0.057	37	-0.058	56	93
GNA15	0.008	0.025	0.056	34	-0.058	52	86
GNA12	0.023	0.018	-10000	0	0	189	189
GNA13	0.035	0.007	-10000	0	0	20	20
MAPT	-0.021	0.076	0.17	10	-0.19	58	68
GNA11	0.011	0.023	0.057	38	-0.058	35	73
Rac1/GTP	-0.008	0.22	-10000	0	-0.85	31	31
MMP2	-0.018	0.1	-10000	0	-0.31	54	54

×

TCGA08_retinoblastoma

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
CDKN2B	0.003	0.027	-10000	0	-0.051	59	59
CDKN2C	-0.009	0.021	-10000	0	-0.037	109	109
CDKN2A	0.005	0.014	-10000	0	-10000	0	0
CCND2	-0.002	0.019	0.11	6	-10000	0	6
RB1	-0.046	0.092	0.16	2	-0.19	142	144
CDK4	-0.001	0.021	0.13	6	-10000	0	6
CDK6	-0.001	0.02	0.13	6	-10000	0	6
G1/S progression	0.056	0.098	0.19	163	-0.16	2	165

×

Syndecan-4-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
PTK2	-0.032	0.16	-10000	0	-0.46	43	43
Syndecan-4/Syndesmos	-0.14	0.28	-10000	0	-0.73	63	63
positive regulation of JNK cascade	-0.13	0.26	-10000	0	-0.61	77	77
Syndecan-4/ADAM12	-0.13	0.28	-10000	0	-0.74	62	62
CCL5	0.033	0.011	-10000	0	0	54	54
Rac1/GDP	0.017	0.02	-10000	0	-0.13	5	5
DNM2	0.035	0.008	-10000	0	0	27	27
ITGA5	0.033	0.012	-10000	0	0	58	58
SDCBP	0.035	0.007	-10000	0	0	21	21
PLG	0.029	0.024	-10000	0	-0.044	37	37
ADAM12	0.024	0.018	-10000	0	0	177	177
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.024	0.022	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.14	0.28	-10000	0	-0.73	63	63
Syndecan-4/CXCL12/CXCR4	-0.14	0.28	-10000	0	-0.66	77	77
Syndecan-4/Laminin alpha3	-0.12	0.29	-10000	0	-0.73	63	63
MDK	0.03	0.014	-10000	0	0	92	92
Syndecan-4/FZD7	-0.14	0.3	-10000	0	-0.64	92	92
Syndecan-4/Midkine	-0.13	0.3	-10000	0	-0.67	80	80
FZD7	0.026	0.017	-10000	0	0	143	143
Syndecan-4/FGFR1/FGF	-0.096	0.28	-10000	0	-0.69	60	60
THBS1	0.03	0.014	-10000	0	0	92	92
integrin-mediated signaling pathway	-0.13	0.28	-10000	0	-0.63	83	83
positive regulation of MAPKKK cascade	-0.13	0.26	-10000	0	-0.61	77	77
Syndecan-4/TACI	-0.12	0.29	-10000	0	-0.74	63	63
CXCR4	0.029	0.015	-10000	0	0	103	103
cell adhesion	-0.01	0.055	0.21	3	-0.25	18	21
Syndecan-4/Dynamin	-0.12	0.29	-10000	0	-0.72	63	63
Syndecan-4/TSP1	-0.13	0.28	-10000	0	-0.75	61	61
Syndecan-4/GIPC	-0.12	0.29	-10000	0	-0.72	63	63
Syndecan-4/RANTES	-0.13	0.29	-10000	0	-0.73	63	63
ITGB1	0.026	0.017	-10000	0	0	144	144
LAMA1	0	0	-10000	0	-10000	0	0
LAMA3	0.033	0.011	-10000	0	0	48	48
RAC1	0.025	0.017	-10000	0	0	163	163
PRKCA	0.004	0.12	1	6	-10000	0	6
Syndecan-4/alpha-Actinin	-0.13	0.3	-10000	0	-0.65	85	85
TFPI	0.029	0.015	-10000	0	0	103	103
F2	0.01	0.042	-10000	0	-0.044	183	183
alpha5/beta1 Integrin	0.028	0.043	-10000	0	-0.14	21	21
positive regulation of cell adhesion	-0.13	0.27	-10000	0	-0.7	63	63
ACTN1	0.028	0.016	-10000	0	0	119	119
TNC	0.028	0.016	-10000	0	0	121	121
Syndecan-4/CXCL12	-0.14	0.28	-10000	0	-0.74	62	62
FGF6	0.035	0.008	-10000	0	0	28	28
RHOA	0.035	0.007	-10000	0	0	21	21
CXCL12	0.022	0.018	-10000	0	0	206	206
TNFRSF13B	0.036	0.005	-10000	0	0	9	9
FGF2	0.035	0.008	-10000	0	0	25	25
FGFR1	0.036	0.005	-10000	0	0	9	9
Syndecan-4/PI-4-5-P2	-0.14	0.28	-10000	0	-0.73	63	63
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.028	0.025	-10000	0	-0.045	41	41
cell migration	-0.011	0.016	-10000	0	-10000	0	0
PRKCD	0.028	0.024	-10000	0	-0.044	37	37
vasculogenesis	-0.13	0.27	-10000	0	-0.7	62	62
SDC4	-0.14	0.3	-10000	0	-0.8	62	62
Syndecan-4/Tenascin C	-0.13	0.3	-10000	0	-0.67	82	82
Syndecan-4/PI-4-5-P2/PKC alpha	-0.019	0.018	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.12	0.29	-10000	0	-0.74	64	64
MMP9	0.011	0.024	-10000	0	-0.042	39	39
Rac1/GTP	-0.01	0.057	0.21	3	-0.26	18	21
cytoskeleton organization	-0.13	0.26	-10000	0	-0.69	64	64
GIPC1	0.035	0.008	-10000	0	0	24	24
Syndecan-4/TFPI	-0.13	0.29	-10000	0	-0.7	71	71

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.005	0.11	0.24	51	-10000	0	51
GNAI2	0.034	0.01	-10000	0	0	44	44
S1P/S1P5/G12	0.01	0.031	-10000	0	-0.11	28	28
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.03	0.014	-10000	0	0	87	87
RhoA/GTP	0.005	0.11	-10000	0	-0.24	51	51
negative regulation of cAMP metabolic process	-0.008	0.099	-10000	0	-0.2	83	83
GNAZ	0.031	0.013	-10000	0	0	80	80
GNAI3	0.036	0.006	-10000	0	0	14	14
GNA12	0.023	0.018	-10000	0	0	189	189
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.009	0.1	-10000	0	-0.2	83	83
RhoA/GDP	0.024	0.019	-10000	0	-0.13	7	7
RHOA	0.035	0.007	-10000	0	0	21	21
GNAI1	0.018	0.018	-10000	0	0	262	262

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.011	0.003	0	34	-10000	0	34
GNB1/GNG2	0.039	0.031	-10000	0	-0.11	20	20
regulation of S phase of mitotic cell cycle	-0.004	0.08	-10000	0	-0.19	69	69
GNAO1	0.03	0.014	-10000	0	0	87	87
HRAS	0.034	0.01	-10000	0	0	36	36
SHBG/T-DHT	0.024	0.004	-10000	0	-10000	0	0
PELP1	0.035	0.007	-10000	0	0	17	17
AKT1	-0.01	0.004	0	54	-10000	0	54
MAP2K1	-0.029	0.083	0.18	29	-0.18	69	98
T-DHT/AR	0.025	0.009	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	0.003	61	-0.006	79	140
GNAI2	0.034	0.01	-10000	0	0	44	44
GNAI3	0.036	0.006	-10000	0	0	14	14
GNAI1	0.018	0.018	-10000	0	0	262	262
mol:GDP	-0.019	0.036	-10000	0	-0.15	15	15
cell proliferation	-0.053	0.19	0.27	17	-0.41	86	103
PIK3CA	0.031	0.014	-10000	0	0	82	82
FOS	-0.084	0.28	0.32	7	-0.69	84	91
mol:Ca2+	-0.004	0.02	0.031	1	-0.054	60	61
MAPK3	-0.037	0.14	0.26	17	-0.3	75	92
MAPK1	-0.036	0.16	0.24	5	-0.37	60	65
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	0	0.002	0.003	59	-0.004	77	136
cAMP biosynthetic process	-0.002	0.013	-10000	0	-10000	0	0
GNG2	0	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.002	0.003	59	-0.004	77	136
HRAS/GTP	0.041	0.066	-10000	0	-0.096	72	72
actin cytoskeleton reorganization	0.02	0.054	-10000	0	-0.12	43	43
SRC	0.034	0.009	-10000	0	0	34	34
voltage-gated calcium channel activity	0	0.002	0.003	59	-0.004	77	136
PI3K	0.019	0.064	-10000	0	-0.13	72	72
apoptosis	0.043	0.19	0.42	85	-0.26	13	98
T-DHT/AR/PELP1	0.043	0.025	-10000	0	-0.11	8	8
HRAS/GDP	0.01	0.062	-10000	0	-0.18	17	17
CREB1	-0.064	0.19	0.26	13	-0.45	86	99
RAC1-CDC42/GTP	0.028	0.06	-10000	0	-0.13	43	43
AR	0.035	0.008	-10000	0	0	22	22
GNB1	0.035	0.007	-10000	0	0	20	20
RAF1	-0.02	0.078	0.19	29	-0.22	14	43
RAC1-CDC42/GDP	0.022	0.054	-10000	0	-0.17	12	12
T-DHT/AR/PELP1/Src	0.058	0.034	-10000	0	-0.1	9	9
MAP2K2	-0.032	0.076	0.17	20	-0.17	66	86
T-DHT/AR/PELP1/Src/PI3K	-0.004	0.081	-10000	0	-0.19	69	69
GNAZ	0.031	0.013	-10000	0	0	80	80
SHBG	0.036	0.006	-10000	0	0	15	15
Gi family/GNB1/GNG2/GDP	-0.038	0.17	-10000	0	-0.48	48	48
mol:T-DHT	0	0.001	0.002	1	-0.004	25	26
RAC1	0.025	0.017	-10000	0	0	163	163
GNRH1	-0.011	0.002	0	12	-10000	0	12
Gi family/GTP	-0.006	0.083	-10000	0	-0.19	62	62
CDC42	0.035	0.008	-10000	0	0	26	26

×

S1P4 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.03	0.014	-10000	0	0	87	87
CDC42/GTP	0.005	0.11	-10000	0	-0.27	39	39
PLCG1	-0.012	0.095	0.12	5	-0.2	84	89
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.034	0.01	-10000	0	0	44	44
GNAI3	0.036	0.006	-10000	0	0	14	14
G12/G13	0.025	0.048	-10000	0	-0.14	28	28
cell migration	0.005	0.1	-10000	0	-0.27	39	39
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
MAPK3	-0.013	0.098	0.12	4	-0.2	89	93
MAPK1	-0.006	0.092	0.12	5	-0.19	79	84
S1P/S1P5/Gi	-0.009	0.1	-10000	0	-0.2	83	83
GNAI1	0.018	0.018	-10000	0	0	262	262
CDC42/GDP	0.026	0.006	-10000	0	-10000	0	0
S1P/S1P5/G12	0.01	0.031	-10000	0	-0.11	28	28
RHOA	0.041	0.1	0.19	156	-0.18	2	158
S1P/S1P4/Gi	-0.009	0.1	-10000	0	-0.2	83	83
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.031	0.013	-10000	0	0	80	80
S1P/S1P4/G12/G13	0.023	0.038	-10000	0	-0.1	28	28
GNA12	0.023	0.018	-10000	0	0	189	189
GNA13	0.035	0.007	-10000	0	0	20	20
CDC42	0.035	0.008	-10000	0	0	26	26

×

Syndecan-1-mediated 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
TGFB1	0.032	0.012	-10000	0	0	66	66
CCL5	0.033	0.011	-10000	0	0	54	54
SDCBP	0.035	0.007	-10000	0	0	21	21
FGFR/FGF2/Syndecan-1	0.015	0.1	0.21	24	-0.25	11	35
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	0.018	0.11	0.22	18	-0.25	13	31
Syndecan-1/Syntenin	0.026	0.11	0.24	24	-0.24	15	39
MAPK3	0.005	0.1	0.2	20	-0.24	20	40
HGF/MET	0.032	0.027	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.032	0.012	-10000	0	0	66	66
BSG	0.032	0.012	-10000	0	0	62	62
keratinocyte migration	0.018	0.1	0.22	18	-0.24	13	31
Syndecan-1/RANTES	0.021	0.11	0.25	17	-0.25	12	29
Syndecan-1/CD147	0.026	0.12	0.24	14	-0.25	16	30
Syndecan-1/Syntenin/PIP2	0.024	0.11	0.22	24	-0.24	15	39
LAMA5	0.032	0.012	-10000	0	0	66	66
positive regulation of cell-cell adhesion	0.023	0.11	0.22	24	-0.23	15	39
MMP7	0.027	0.016	-10000	0	0	138	138
HGF	0.024	0.018	-10000	0	0	177	177
Syndecan-1/CASK	-0.001	0.087	0.15	5	-0.24	12	17
Syndecan-1/HGF/MET	0.024	0.09	0.26	7	-0.25	6	13
regulation of cell adhesion	-0.003	0.11	0.24	29	-0.25	16	45
HPSE	0.032	0.012	-10000	0	0	59	59
positive regulation of cell migration	0.015	0.1	0.21	24	-0.25	11	35
SDC1	0.012	0.097	0.17	36	-0.25	11	47
Syndecan-1/Collagen	0.015	0.1	0.21	24	-0.25	11	35
PPIB	0.034	0.009	-10000	0	0	36	36
MET	0.023	0.018	-10000	0	0	190	190
PRKACA	0.035	0.008	-10000	0	0	24	24
MMP9	0.017	0.018	-10000	0	0	280	280
MAPK1	0.004	0.1	0.2	18	-0.25	16	34
homophilic cell adhesion	0.017	0.1	0.22	28	-0.25	11	39
MMP1	0.032	0.013	-10000	0	0	72	72

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.032	0.012	-10000	0	0	62	62
LAT2	-0.016	0.094	0.14	2	-0.28	48	50
AP1	-0.062	0.18	-10000	0	-0.39	74	74
mol:PIP3	0.021	0.14	0.26	37	-0.28	46	83
IKBKB	0.011	0.094	0.19	36	-0.19	39	75
AKT1	-0.055	0.1	0.24	12	-0.27	46	58
IKBKG	0.01	0.093	0.19	33	-0.19	38	71
MS4A2	0.039	0.007	0.065	4	0	4	8
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.031	0.013	-10000	0	0	82	82
MAP3K1	-0.023	0.12	0.23	9	-0.31	52	61
mol:Ca2+	0.022	0.12	0.23	42	-0.22	46	88
LYN	0.03	0.015	-10000	0	-0.003	80	80
CBLB	-0.022	0.11	0.15	3	-0.28	67	70
SHC1	0.033	0.011	-10000	0	0	52	52
RasGAP/p62DOK	0.048	0.053	-10000	0	-0.12	37	37
positive regulation of cell migration	-0.011	0.003	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
PLD2	-0.032	0.072	0.26	15	-0.17	12	27
PTPN13	-0.036	0.19	-10000	0	-0.6	39	39
PTPN11	0.031	0.022	-10000	0	-0.035	47	47
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.036	0.11	0.24	8	-0.32	39	47
SYK	0.03	0.015	-10000	0	-0.033	7	7
GRB2	0.036	0.007	-10000	0	0	18	18
LAT/PLCgamma1/GRB2/SLP76/GADs	0.011	0.12	0.21	6	-0.27	55	61
LAT	-0.021	0.11	0.16	2	-0.28	65	67
PAK2	-0.023	0.13	0.21	10	-0.32	55	65
NFATC2	-0.013	0.013	-10000	0	-0.043	72	72
HRAS	-0.021	0.14	0.19	14	-0.32	65	79
GAB2	0.033	0.011	-10000	0	0	48	48
PLA2G1B	-0.007	0.19	-10000	0	-0.91	20	20
Fc epsilon R1	0.042	0.068	-10000	0	-0.11	73	73
Antigen/IgE/Fc epsilon R1	0.044	0.061	-10000	0	-0.096	72	72
mol:GDP	-0.013	0.14	0.21	10	-0.35	54	64
JUN	0.034	0.01	-10000	0	0	41	41
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.032	0.012	-10000	0	0	63	63
FOS	0.025	0.017	-10000	0	0	162	162
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.014	0.12	-10000	0	-0.28	73	73
CHUK	0.011	0.091	0.19	36	-0.18	40	76
KLRG1	-0.018	0.099	0.13	8	-0.22	80	88
VAV1	-0.021	0.11	0.16	4	-0.27	64	68
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.023	0.11	0.16	2	-0.28	68	70
negative regulation of mast cell degranulation	-0.021	0.092	0.12	2	-0.22	71	73
BTK	-0.012	0.14	-10000	0	-0.37	46	46
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.026	0.11	-10000	0	-0.18	145	145
GAB2/PI3K/SHP2	-0.069	0.075	-10000	0	-0.2	88	88
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.005	0.078	-10000	0	-0.2	62	62
RAF1	-0.007	0.2	-10000	0	-0.97	20	20
Fc epsilon R1/FcgammaRIIB/SHIP	0.023	0.097	-10000	0	-0.13	130	130
FCER1G	0.029	0.016	-10000	0	0	113	113
FCER1A	0.033	0.013	-10000	0	-0.032	9	9
Antigen/IgE/Fc epsilon R1/Fyn	0.041	0.083	-10000	0	-0.11	102	102
MAPK3	-0.005	0.19	-10000	0	-0.9	20	20
MAPK1	-0.014	0.2	-10000	0	-0.95	20	20
NFKB1	0.035	0.007	-10000	0	0	18	18
MAPK8	-0.13	0.28	-10000	0	-0.55	148	148
DUSP1	0.031	0.013	-10000	0	0	76	76
NF-kappa-B/RelA	0.018	0.066	0.14	34	-0.13	40	74
actin cytoskeleton reorganization	-0.027	0.2	-10000	0	-0.6	37	37
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.011	0.15	0.23	8	-0.31	71	79
FER	-0.021	0.12	0.16	3	-0.27	71	74
RELA	0.036	0.004	-10000	0	0	7	7
ITK	0.003	0.037	-10000	0	-0.3	2	2
SOS1	0	0	-10000	0	-10000	0	0
PLCG1	-0.002	0.14	0.24	16	-0.31	61	77
cytokine secretion	0.01	0.046	0.087	29	-0.088	51	80
SPHK1	-0.019	0.12	0.15	4	-0.28	66	70
PTK2	-0.03	0.2	-10000	0	-0.64	37	37
NTAL/PLCgamma1/GRB2/SLP76/GADs	0.028	0.13	0.24	15	-0.28	50	65
EDG1	-0.011	0.003	-10000	0	-10000	0	0
mol:DAG	0.002	0.15	0.25	31	-0.3	59	90
MAP2K2	-0.006	0.19	-10000	0	-0.92	20	20
MAP2K1	-0.017	0.18	-10000	0	-0.92	20	20
MAP2K7	0.035	0.007	-10000	0	0	22	22
KLRG1/SHP2	0.002	0.098	0.2	10	-0.23	55	65
MAP2K4	0.024	0.14	-10000	0	-0.88	12	12
Fc epsilon R1/FcgammaRIIB	0.025	0.1	-10000	0	-0.14	130	130
mol:Choline	-0.032	0.071	0.25	15	-0.17	12	27
SHC/Grb2/SOS1	0.012	0.13	0.2	1	-0.27	68	69
FYN	0.03	0.014	-10000	0	0	88	88
DOK1	0.037	0.002	-10000	0	0	2	2
PXN	-0.031	0.19	-10000	0	-0.58	38	38
HCLS1	-0.025	0.13	0.16	7	-0.32	67	74
PRKCB	0.013	0.12	0.22	36	-0.23	52	88
FCGR2B	0.02	0.018	-10000	0	0	226	226
IGHE	-0.001	0.004	0.02	3	-10000	0	3
KLRG1/SHIP	-0.022	0.094	0.12	2	-0.22	71	73
LCP2	0.032	0.013	-10000	0	0	75	75
PLA2G4A	-0.016	0.12	0.16	10	-0.31	61	71
RASA1	0.035	0.009	-10000	0	0	30	30
mol:Phosphatidic acid	-0.032	0.071	0.25	15	-0.17	12	27
IKK complex	0.008	0.079	0.18	28	-0.16	22	50
WIPF1	0	0	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.068	0.06	-10000	0	-0.12	33	33
MAP4K1	0.035	0.008	-10000	0	0	27	27
MAP3K8	0.022	0.018	-10000	0	0	200	200
PRKCB	0	0	-10000	0	-10000	0	0
DBNL	0	0	-10000	0	-10000	0	0
CRKL	0.035	0.008	-10000	0	0	28	28
MAP3K1	-0.001	0.055	0.13	1	-0.16	44	45
JUN	-0.14	0.24	-10000	0	-0.52	143	143
MAP3K7	-0.001	0.053	-10000	0	-0.17	38	38
GRAP2	0.034	0.01	-10000	0	0	37	37
CRK	0.035	0.008	-10000	0	0	23	23
MAP2K4	-0.016	0.071	0.15	1	-0.24	25	26
LAT	0.036	0.005	-10000	0	0	9	9
LCP2	0.031	0.013	-10000	0	0	75	75
MAPK8	-0.14	0.25	-10000	0	-0.54	143	143
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.009	0.06	-10000	0	-0.16	46	46
LAT/GRAP2/SLP76/HPK1/HIP-55	0.063	0.056	-10000	0	-0.11	33	33

×

amb2 Integrin signaling

Figure S27. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S27. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.028	0.087	-10000	0	-0.14	90	90
alphaM/beta2 Integrin/GPIbA	0.048	0.071	-10000	0	-0.12	62	62
alphaM/beta2 Integrin/proMMP-9	-0.01	0.091	-10000	0	-0.14	139	139
PLAUR	0.03	0.014	-10000	0	0	90	90
HMGB1	0.039	0.014	0.083	1	-10000	0	1
alphaM/beta2 Integrin/Talin	0.038	0.073	-10000	0	-0.13	57	57
AGER	0.041	0.01	0.08	2	-10000	0	2
RAP1A	0.036	0.005	-10000	0	0	10	10
SELPLG	0.036	0.004	-10000	0	0	7	7
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.075	0.086	-10000	0	-0.12	54	54
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.017	0.018	-10000	0	0	280	280
CYR61	0.025	0.017	-10000	0	0	166	166
TLN1	0.029	0.015	-10000	0	0	101	101
Rap1/GTP	0.028	0.072	-10000	0	-0.22	18	18
RHOA	0.035	0.007	-10000	0	0	21	21
P-selectin oligomer	0.036	0.006	-10000	0	0	15	15
MYH2	0.024	0.072	0.19	3	-0.27	8	11
MST1R	0.035	0.008	-10000	0	0	23	23
leukocyte activation during inflammatory response	0.055	0.066	-10000	0	-0.11	57	57
APOB	0.036	0.006	-10000	0	0	13	13
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.029	0.015	-10000	0	0	109	109
JAM3	0.033	0.011	-10000	0	0	52	52
GP1BA	0.036	0.005	-10000	0	0	10	10
alphaM/beta2 Integrin/CTGF	0.02	0.088	-10000	0	-0.13	104	104
alphaM/beta2 Integrin	0.023	0.075	0.17	1	-0.24	17	18
JAM3 homodimer	0.033	0.011	-10000	0	0	52	52
ICAM2	0.034	0.009	-10000	0	0	32	32
ICAM1	0.031	0.014	-10000	0	0	83	83
phagocytosis triggered by activation of immune response cell surface activating receptor	0.024	0.076	0.17	1	-0.23	18	19
cell adhesion	0.047	0.07	-10000	0	-0.12	62	62
NFKB1	-0.003	0.08	0.22	16	-10000	0	16
THY1	0.031	0.014	-10000	0	0	82	82
RhoA/GDP	0.024	0.019	-10000	0	-0.13	7	7
Lipoprotein(a)	0.045	0.014	-10000	0	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	0.037	0.1	-10000	0	-0.15	102	102
IL6	-0.016	0.039	-10000	0	-10000	0	0
ITGB2	0.033	0.019	0.078	1	-10000	0	1
elevation of cytosolic calcium ion concentration	0.026	0.09	-10000	0	-0.15	72	72
alphaM/beta2 Integrin/JAM2/JAM3	0.048	0.1	-10000	0	-0.15	89	89
JAM2	0.033	0.012	-10000	0	0	57	57
alphaM/beta2 Integrin/ICAM1	0.076	0.078	-10000	0	-0.12	47	47
alphaM/beta2 Integrin/uPA/Plg	0.036	0.085	-10000	0	-0.13	66	66
RhoA/GTP	0.029	0.073	0.19	3	-0.28	8	11
positive regulation of phagocytosis	0.016	0.1	0.19	2	-0.25	45	47
Ron/MSP	0.051	0.014	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPAR/uPA	0.027	0.092	-10000	0	-0.15	72	72
alphaM/beta2 Integrin/uPAR	0.036	0.079	-10000	0	-0.14	68	68
PLAU	0.019	0.018	-10000	0	0	239	239
PLAT	0.027	0.016	-10000	0	0	129	129
actin filament polymerization	0.027	0.073	0.21	6	-0.26	8	14
MST1	0.035	0.008	-10000	0	0	27	27
alphaM/beta2 Integrin/lipoprotein(a)	0.062	0.07	-10000	0	-0.11	57	57
TNF	0.005	0.089	0.21	19	-10000	0	19
RAP1B	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.017	0.075	-10000	0	-0.14	68	68
fibrinolysis	0.035	0.083	-10000	0	-0.13	66	66
HCK	0.027	0.016	-10000	0	0	141	141
dendritic cell antigen processing and presentation	0.024	0.076	0.17	1	-0.23	18	19
VTN	0.036	0.004	-10000	0	0	5	5
alphaM/beta2 Integrin/CYR61	0.01	0.095	-10000	0	-0.14	125	125
LPA	0.034	0.009	-10000	0	0	33	33
LRP1	0.032	0.013	-10000	0	0	70	70
cell migration	-0.001	0.11	0.16	12	-0.15	146	158
FN1	0.035	0.009	-10000	0	0	30	30
alphaM/beta2 Integrin/Thy1	0.029	0.087	-10000	0	-0.14	92	92
MPO	0.036	0.004	-10000	0	0	6	6
KNG1	0.035	0.008	-10000	0	0	28	28
RAP1/GDP	0.024	0.007	-10000	0	-0.11	1	1
ROCK1	0.024	0.073	0.19	3	-0.27	10	13
ELA2	0.035	0.008	-10000	0	0	28	28
PLG	0.034	0.009	-10000	0	0	35	35
CTGF	0.027	0.016	-10000	0	0	139	139
alphaM/beta2 Integrin/Hck	0.029	0.092	-10000	0	-0.18	69	69
ITGAM	0.042	0.01	0.08	2	-10000	0	2
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.071	0.074	-10000	0	-0.12	56	56
HP	0.027	0.016	-10000	0	0	137	137
leukocyte adhesion	0.021	0.12	-10000	0	-0.26	36	36
SELP	0.036	0.006	-10000	0	0	15	15

×

IL2 signaling events mediated by STAT5

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
GAB2	0.033	0.014	-10000	0	-0.005	57	57
ELF1	0.042	0.016	-10000	0	-10000	0	0
CCNA2	0.028	0.016	-10000	0	0	118	118
PIK3CA	0.03	0.015	-10000	0	-0.002	89	89
JAK3	0.034	0.012	-10000	0	-0.008	34	34
PIK3R1	0.032	0.014	-10000	0	-0.002	68	68
JAK1	0.034	0.012	-10000	0	-0.004	46	46
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.02	0.18	0.24	2	-0.53	39	41
SHC1	0.032	0.014	-10000	0	-0.004	60	60
SP1	-0.01	0.12	-10000	0	-0.27	87	87
IL2RA	0.011	0.012	-10000	0	-10000	0	0
IL2RB	0.032	0.014	-10000	0	-0.004	61	61
SOS1	0	0.002	-10000	0	-10000	0	0
IL2RG	0.035	0.011	-10000	0	-0.006	30	30
G1/S transition of mitotic cell cycle	-0.068	0.27	0.27	12	-0.58	95	107
PTPN11	0.035	0.01	-10000	0	-0.012	18	18
CCND2	-0.072	0.19	-10000	0	-0.5	87	87
LCK	0.035	0.01	-10000	0	-0.008	25	25
GRB2	0.035	0.01	-10000	0	-0.008	25	25
IL2	0.036	0.009	-10000	0	-0.013	16	16
CDK6	0.024	0.018	-10000	0	0	177	177
CCND3	-0.026	0.2	0.36	3	-0.75	27	30

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.013	0.062	0.14	2	-0.13	70	72
EPHB2	0.034	0.01	-10000	0	0	40	40
Syndecan-2/TACI	0.017	0.056	0.14	2	-0.12	66	68
LAMA1	0	0	-10000	0	-10000	0	0
Syndecan-2/alpha2 ITGB1	0.021	0.074	-10000	0	-0.12	84	84
HRAS	0.034	0.009	-10000	0	0	36	36
Syndecan-2/CASK	-0.009	0.042	-10000	0	-0.11	69	69
ITGA5	0.033	0.012	-10000	0	0	58	58
BAX	-0.008	0.073	-10000	0	-0.9	3	3
EPB41	0.036	0.005	-10000	0	0	10	10
positive regulation of cell-cell adhesion	0.012	0.055	-10000	0	-0.12	73	73
LAMA3	0.033	0.011	-10000	0	0	48	48
EZR	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.019	0.018	-10000	0	0	245	245
Syndecan-2/MMP2	0.008	0.063	0.14	1	-0.14	66	67
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.018	0.055	-10000	0	-0.14	42	42
dendrite morphogenesis	0.016	0.054	0.14	2	-0.12	61	63
Syndecan-2/GM-CSF	0.017	0.056	0.14	2	-0.12	65	67
determination of left/right symmetry	0.007	0.023	0.086	5	-0.24	4	9
Syndecan-2/PKC delta	0.016	0.055	0.14	1	-0.12	62	63
GNB2L1	0.037	0.002	-10000	0	0	2	2
MAPK3	-0.023	0.051	0.12	34	-0.19	4	38
MAPK1	-0.022	0.053	0.12	31	-0.2	9	40
Syndecan-2/RACK1	0.029	0.065	0.14	3	-0.11	78	81
NF1	0.036	0.003	-10000	0	0	4	4
FGFR/FGF/Syndecan-2	0.007	0.023	0.086	5	-0.24	4	9
ITGA2	0.029	0.015	-10000	0	0	112	112
MAPK8	-0.004	0.038	0.13	3	-0.39	3	6
Syndecan-2/alpha2/beta1 Integrin	0.007	0.064	0.14	1	-0.11	92	93
Syndecan-2/Kininogen	0.017	0.055	0.14	2	-0.12	63	65
ITGB1	0.026	0.017	-10000	0	0	144	144
SRC	-0.026	0.052	0.17	11	-0.19	8	19
Syndecan-2/CASK/Protein 4.1	0.015	0.05	-10000	0	-0.11	68	68
extracellular matrix organization	0.014	0.053	0.14	1	-0.12	57	58
actin cytoskeleton reorganization	0.013	0.062	0.14	2	-0.13	70	72
Syndecan-2/Caveolin-2/Ras	0.006	0.068	0.15	1	-0.13	78	79
Syndecan-2/Laminin alpha3	0.016	0.053	0.14	1	-0.12	61	62
Syndecan-2/RasGAP	0.036	0.08	-10000	0	-0.12	91	91
alpha5/beta1 Integrin	0.028	0.043	-10000	0	-0.14	21	21
PRKCD	0.034	0.01	-10000	0	0	40	40
Syndecan-2 dimer	0.016	0.054	0.14	2	-0.12	61	63
GO:0007205	0.001	0.01	-10000	0	-0.11	4	4
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.013	0.067	0.19	2	-0.13	75	77
RHOA	0.035	0.007	-10000	0	0	21	21
SDCBP	0.035	0.007	-10000	0	0	21	21
TNFRSF13B	0.036	0.005	-10000	0	0	9	9
RASA1	0.035	0.009	-10000	0	0	30	30
alpha2/beta1 Integrin	0.018	0.055	-10000	0	-0.14	42	42
Syndecan-2/Synbindin	0.016	0.06	0.14	2	-0.13	67	69
TGFB1	0.032	0.012	-10000	0	0	66	66
CASP3	-0.018	0.055	0.12	32	-0.18	10	42
FN1	0.035	0.009	-10000	0	0	30	30
Syndecan-2/IL8	-0.004	0.07	-10000	0	-0.18	62	62
SDC2	0.007	0.023	0.086	5	-0.24	4	9
KNG1	0.035	0.008	-10000	0	0	28	28
Syndecan-2/Neurofibromin	0.017	0.057	0.14	2	-0.12	68	70
TRAPPC4	0.036	0.006	-10000	0	0	16	16
CSF2	0.036	0.005	-10000	0	0	8	8
Syndecan-2/TGFB1	0.014	0.053	0.14	1	-0.12	57	58
Syndecan-2/Syntenin/PI-4-5-P2	0.013	0.055	-10000	0	-0.12	73	73
Syndecan-2/Ezrin	0.014	0.054	-10000	0	-0.11	70	70
PRKACA	-0.021	0.052	0.12	35	-0.19	4	39
angiogenesis	-0.004	0.07	-10000	0	-0.18	62	62
MMP2	0.029	0.015	-10000	0	0	109	109
IL8	0.019	0.018	-10000	0	0	244	244
calcineurin-NFAT signaling pathway	0.017	0.056	0.14	2	-0.12	66	68

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.046	0.081	0.32	3	-10000	0	3
CRKL	0.042	0.089	0.16	173	-10000	0	173
mol:DAG	0.017	0.061	0.2	3	-0.19	26	29
HRAS	0.041	0.098	0.23	56	-0.19	2	58
MAPK8	0.01	0.074	0.16	78	-10000	0	78
RAP1A	0.048	0.093	0.17	157	-10000	0	157
GAB1	0.039	0.086	0.16	160	-10000	0	160
MAPK14	0.032	0.1	0.17	149	-10000	0	149
EPO	0.027	0.02	-10000	0	-0.033	2	2
PLCG1	0.017	0.061	0.2	3	-0.19	26	29
EPOR/TRPC2/IP3 Receptors	0.042	0.013	-10000	0	-0.033	2	2
RAPGEF1	0.035	0.007	-10000	0	0	18	18
EPO/EPOR (dimer)/SOCS3	0.051	0.038	-10000	0	-10000	0	0
GAB1/SHC/GRB2/SOS1	0.062	0.071	0.21	29	-10000	0	29
EPO/EPOR (dimer)	0.039	0.03	-10000	0	-10000	0	0
IRS2	0.037	0.088	0.16	152	-0.16	4	156
STAT1	0.02	0.066	0.22	6	-0.19	27	33
STAT5B	0.02	0.066	0.21	6	-0.19	28	34
cell proliferation	0.007	0.074	0.16	80	-10000	0	80
GAB1/SHIP/PIK3R1/SHP2/SHC	0.039	0.063	0.16	3	-0.18	6	9
TEC	0.047	0.093	0.16	184	-10000	0	184
SOCS3	0.036	0.005	-10000	0	0	8	8
STAT1 (dimer)	0.021	0.066	0.22	7	-0.19	27	34
JAK2	0.037	0.018	-10000	0	-10000	0	0
PIK3R1	0.032	0.012	-10000	0	0	63	63
EPO/EPOR (dimer)/JAK2	0.048	0.053	0.22	11	-10000	0	11
EPO/EPOR	0.039	0.03	-10000	0	-10000	0	0
LYN	0.033	0.014	-10000	0	-10000	0	0
TEC/VAV2	0.059	0.07	0.21	34	-10000	0	34
elevation of cytosolic calcium ion concentration	0.042	0.013	-10000	0	-0.033	2	2
SHC1	0.033	0.011	-10000	0	0	52	52
EPO/EPOR (dimer)/LYN	0.041	0.059	-10000	0	-0.13	29	29
mol:IP3	0.017	0.061	0.2	3	-0.19	26	29
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.021	0.094	0.16	135	-0.17	12	147
SH2B3	-0.001	0.006	0.026	8	-10000	0	8
NFKB1	0.032	0.099	0.17	146	-10000	0	146
EPO/EPOR (dimer)/JAK2/SOCS3	0.015	0.015	-10000	0	-10000	0	0
PTPN6	0.046	0.092	0.17	161	-10000	0	161
TEC/VAV2/GRB2	0.082	0.07	0.23	34	-10000	0	34
EPOR	0.042	0.013	-10000	0	-0.033	2	2
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.061	0.071	0.21	29	-10000	0	29
SOS1	0	0	-10000	0	-10000	0	0
PLCG2	0.032	0.012	-10000	0	0	63	63
CRKL/CBL/C3G	0.08	0.066	0.22	28	-10000	0	28
VAV2	0.045	0.092	0.16	173	-10000	0	173
CBL	0.046	0.092	0.16	150	-10000	0	150
SHC/Grb2/SOS1	0.023	0.035	-10000	0	-0.11	8	8
STAT5A	0.02	0.065	0.21	5	-0.19	27	32
GRB2	0.035	0.007	-10000	0	0	18	18
STAT5 (dimer)	0.036	0.072	0.27	5	-0.21	7	12
LYN/PLCgamma2	0.025	0.074	-10000	0	-0.18	55	55
PTPN11	0.036	0.005	-10000	0	0	11	11
BTK	0.045	0.093	0.16	182	-10000	0	182
BCL2	0.047	0.082	0.32	1	-10000	0	1

×

IL23-mediated signaling events

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
CCL2	-0.064	0.61	0.76	36	-1	129	165
IL23A	0.091	0.37	0.79	20	-0.98	20	40
NF kappa B1 p50/RelA/I kappa B alpha	0.082	0.34	0.62	31	-0.82	25	56
positive regulation of T cell mediated cytotoxicity	0.092	0.4	0.78	37	-0.91	25	62
ITGA3	0.09	0.36	0.75	23	-0.86	24	47
IL17F	0.036	0.27	0.52	33	-0.58	27	60
IL12B	0.061	0.081	0.2	69	-0.075	2	71
STAT1 (dimer)	0.072	0.36	0.65	36	-0.89	25	61
CD4	0.073	0.42	0.74	37	-1	33	70
IL23	0.098	0.36	0.74	16	-0.94	21	37
IL23R	0.068	0.14	0.29	90	-0.15	10	100
IL1B	0.085	0.4	0.76	30	-1.1	26	56
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	0.099	0.36	0.7	33	-0.84	21	54
TYK2	0.042	0.06	0.15	49	-10000	0	49
STAT4	0.035	0.009	-10000	0	0	29	29
STAT3	0.034	0.01	-10000	0	0	37	37
IL18RAP	0.035	0.008	-10000	0	-0.01	13	13
IL12RB1	0.045	0.06	0.15	52	-10000	0	52
PIK3CA	0.031	0.014	-10000	0	0	82	82
IL12Rbeta1/TYK2	0.055	0.076	0.19	37	-0.14	11	48
IL23R/JAK2	0.1	0.17	0.4	72	-0.19	16	88
positive regulation of chronic inflammatory response	0.092	0.4	0.78	37	-0.91	25	62
natural killer cell activation	-0.005	0.011	-10000	0	-0.032	39	39
JAK2	0.056	0.081	0.2	68	-10000	0	68
PIK3R1	0.032	0.012	-10000	0	0	63	63
NFKB1	0.039	0.009	0.068	2	-10000	0	2
RELA	0.04	0.008	0.068	2	0	7	9
positive regulation of dendritic cell antigen processing and presentation	0.099	0.35	0.73	18	-0.89	21	39
ALOX12B	0.087	0.36	0.7	32	-0.83	24	56
CXCL1	0.097	0.37	0.77	32	-0.83	24	56
T cell proliferation	0.092	0.4	0.78	37	-0.91	25	62
NFKBIA	0.036	0.014	0.068	2	0	57	59
IL17A	0.06	0.24	0.46	52	-0.46	28	80
PI3K	0.048	0.35	0.65	21	-0.86	25	46
IFNG	0.019	0.034	0.099	29	-0.08	6	35
STAT3 (dimer)	0.049	0.34	0.62	28	-0.82	27	55
IL18R1	0.035	0.008	-10000	0	-0.015	11	11
IL23/IL23R/JAK2/TYK2/SOCS3	0.096	0.27	0.56	51	-0.51	18	69
IL18/IL18R	0.062	0.036	-10000	0	-0.12	7	7
macrophage activation	-0.002	0.016	0.039	1	-0.043	14	15
TNF	0.093	0.36	0.73	29	-0.88	22	51
STAT3/STAT4	0.071	0.36	0.62	30	-0.86	26	56
STAT4 (dimer)	0.072	0.36	0.64	31	-0.89	25	56
IL18	0.031	0.013	-10000	0	0	75	75
IL19	0.1	0.36	0.71	30	-0.84	21	51
STAT5A (dimer)	0.086	0.37	0.65	36	-0.88	25	61
STAT1	0.034	0.01	-10000	0	0	40	40
SOCS3	0.036	0.005	-10000	0	0	8	8
CXCL9	0.1	0.36	0.75	32	-0.83	24	56
MPO	0.089	0.36	0.76	19	-0.88	18	37
positive regulation of humoral immune response	0.092	0.4	0.78	37	-0.91	25	62
IL23/IL23R/JAK2/TYK2	0.09	0.4	0.78	37	-0.95	24	61
IL6	0.15	0.37	0.76	44	-0.86	19	63
STAT5A	0.036	0.004	-10000	0	0	5	5
IL2	0.02	0.032	0.076	1	-0.035	123	124
positive regulation of tyrosine phosphorylation of STAT protein	-0.005	0.011	-10000	0	-0.032	39	39
CD3E	0.088	0.36	0.69	37	-0.82	25	62
keratinocyte proliferation	0.092	0.4	0.78	37	-0.91	25	62
NOS2	0.089	0.36	0.69	38	-0.82	25	63

×

Glypican 2 network

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
MDK	0.03	0.014	-9999	0	92	92
GPC2	0	0	-9999	-10000	0	0
GPC2/Midkine	0.007	0.051	-9999	-0.13	57	57
neuron projection morphogenesis	0.007	0.051	-9999	-0.13	57	57

×

Osteopontin-mediated 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
IKK alpha homodimer	0.002	0.079	0.19	3	-0.19	39	42
NF kappa B1 p50/RelA/I kappa B alpha	-0.02	0.12	0.25	1	-0.31	47	48
alphaV/beta3 Integrin/Osteopontin/Src	0.026	0.082	-10000	0	-0.15	80	80
AP1	-0.014	0.15	0.28	6	-0.28	83	89
ILK	-0.032	0.073	0.2	2	-0.24	33	35
bone resorption	-0.04	0.085	0.18	7	-0.23	40	47
PTK2B	0.036	0.006	-10000	0	0	16	16
PYK2/p130Cas	0.045	0.091	-10000	0	-0.16	62	62
ITGAV	0.031	0.026	-10000	0	-0.056	36	36
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.02	0.07	-10000	0	-0.14	74	74
alphaV/beta3 Integrin/Osteopontin	0.05	0.094	-10000	0	-0.16	77	77
MAP3K1	-0.03	0.064	0.22	1	-0.21	27	28
JUN	0.034	0.01	-10000	0	0	41	41
MAPK3	-0.032	0.086	0.18	7	-0.24	42	49
MAPK1	-0.03	0.088	0.17	12	-0.26	39	51
Rac1/GDP	0.017	0.02	-10000	0	-0.13	5	5
NFKB1	0.035	0.007	-10000	0	0	18	18
MAPK8	-0.028	0.061	0.23	1	-0.21	27	28
ITGB3	0.032	0.026	-10000	0	-0.055	40	40
NFKBIA	-0.039	0.11	0.19	5	-0.32	46	51
FOS	0.025	0.017	-10000	0	0	162	162
CD44	0.029	0.015	-10000	0	0	110	110
CHUK	0.025	0.017	-10000	0	0	165	165
PLAU	-0.074	0.26	-10000	0	-0.96	34	34
NF kappa B1 p50/RelA	-0.001	0.13	0.24	3	-0.33	41	44
BCAR1	0	0	-10000	0	-10000	0	0
RELA	0.036	0.004	-10000	0	0	7	7
alphaV beta3 Integrin	0.04	0.058	-10000	0	-0.13	44	44
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.032	0.066	0.19	2	-0.23	29	31
VAV3	-0.026	0.075	0.16	6	-0.23	35	41
MAP3K14	-0.028	0.076	0.17	5	-0.21	34	39
ROCK2	0.035	0.007	-10000	0	0	20	20
SPP1	0.03	0.026	-10000	0	-0.058	30	30
RAC1	0.025	0.017	-10000	0	0	163	163
Rac1/GTP	-0.021	0.072	0.15	4	-0.22	28	32
MMP2	-0.062	0.12	-10000	0	-0.33	62	62

×

PLK2 and PLK4 events

Figure S34. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S34. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.031	0.014	-10000	0	0	83	83
PLK4	0.035	0.007	-10000	0	0	19	19
regulation of centriole replication	-0.011	0.032	0.093	43	-9999	0	43

×

Signaling events mediated by PTP1B

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.035	0.008	-10000	0	0	26	26
Jak2/Leptin Receptor	-0.002	0.13	-10000	0	-0.3	57	57
PTP1B/AKT1	0.003	0.11	0.19	1	-0.25	52	53
FYN	0.03	0.014	-10000	0	0	88	88
p210 bcr-abl/PTP1B	-0.008	0.11	0.18	5	-0.26	45	50
EGFR	0.009	0.017	-10000	0	0	382	382
EGF/EGFR	-0.032	0.089	-10000	0	-0.28	39	39
CSF1	0.036	0.004	-10000	0	0	7	7
AKT1	0.033	0.012	-10000	0	0	54	54
INSR	0.035	0.008	-10000	0	-0.001	24	24
PTP1B/N-cadherin	-0.003	0.12	0.19	2	-0.26	56	58
Insulin Receptor/Insulin	0.022	0.11	-10000	0	-0.25	35	35
HCK	0.027	0.016	-10000	0	0	141	141
CRK	0.035	0.008	-10000	0	0	23	23
TYK2	-0.008	0.12	0.28	21	-0.27	50	71
EGF	0.027	0.024	-10000	0	-0.023	92	92
YES1	0.034	0.01	-10000	0	0	39	39
CAV1	0.01	0.14	0.22	39	-0.28	57	96
TXN	0.035	0.01	-10000	0	0	37	37
PTP1B/IRS1/GRB2	0.009	0.12	0.2	2	-0.26	51	53
cell migration	0.008	0.11	0.26	45	-0.18	5	50
STAT3	0.034	0.01	-10000	0	0	37	37
PRLR	0.038	0.004	-10000	0	-10000	0	0
ITGA2B	0.036	0.003	-10000	0	0	3	3
CSF1R	0.027	0.016	-10000	0	0	132	132
Prolactin Receptor/Prolactin	0.057	0.012	-10000	0	-10000	0	0
FGR	0.033	0.011	-10000	0	0	56	56
PTP1B/p130 Cas	-0.01	0.1	0.15	5	-0.25	46	51
Crk/p130 Cas	0	0.11	0.18	2	-0.25	49	51
DOK1	-0.006	0.1	0.18	9	-0.28	35	44
JAK2	-0.013	0.13	-10000	0	-0.32	57	57
Jak2/Leptin Receptor/Leptin	-0.013	0.12	-10000	0	-0.3	36	36
PIK3R1	0.032	0.012	-10000	0	0	63	63
PTPN1	-0.008	0.11	0.18	5	-0.27	45	50
LYN	0.031	0.013	-10000	0	0	74	74
CDH2	0.033	0.011	-10000	0	0	55	55
SRC	0.017	0.093	-10000	0	-0.48	13	13
ITGB3	0.036	0.003	-10000	0	0	4	4
CAT1/PTP1B	-0.005	0.17	0.26	26	-0.36	63	89
CAPN1	0.036	0.004	-10000	0	0	5	5
CSK	0.035	0.007	-10000	0	0	18	18
PI3K	0.013	0.13	-10000	0	-0.28	47	47
mol:H2O2	0.004	0.005	0.024	5	-10000	0	5
STAT3 (dimer)	-0.011	0.11	-10000	0	-0.28	34	34
negative regulation of transcription	-0.012	0.13	-10000	0	-0.31	57	57
FCGR2A	0.028	0.015	-10000	0	0	117	117
FER	0.037	0.007	-10000	0	0	13	13
alphaIIb/beta3 Integrin	0.053	0.005	-10000	0	-10000	0	0
BLK	0.036	0.007	-10000	0	0	17	17
Insulin Receptor/Insulin/Shc	0.06	0.036	-10000	0	-0.13	8	8
RHOA	0.035	0.007	-10000	0	0	21	21
LEPR	0.035	0.007	-10000	0	0	19	19
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.035	0.007	-10000	0	0	18	18
mol:NADPH	0.001	0.003	-10000	0	-10000	0	0
TRPV6	-0.002	0.15	0.21	11	-0.35	57	68
PRL	0.038	0.007	-10000	0	-10000	0	0
SOCS3	0.022	0.051	-10000	0	-1.1	1	1
SPRY2	0.029	0.018	-10000	0	0	140	140
Insulin Receptor/Insulin/IRS1	0.056	0.046	-10000	0	-0.13	22	22
CSF1/CSF1R	-0.002	0.13	0.2	2	-0.27	56	58
Ras protein signal transduction	-0.009	0.074	0.58	6	-10000	0	6
IRS1	0.033	0.011	-10000	0	0	51	51
INS	0.036	0.007	-10000	0	-0.002	17	17
LEP	0.024	0.017	-10000	0	0	170	170
STAT5B	-0.003	0.1	0.18	3	-0.28	31	34
STAT5A	-0.002	0.1	0.18	3	-0.28	31	34
GRB2	0.035	0.007	-10000	0	0	18	18
PDGFB-D/PDGFRB	0.003	0.12	0.19	2	-0.26	46	48
CSN2	0.012	0.041	-10000	0	-10000	0	0
PIK3CA	0.031	0.014	-10000	0	0	82	82
LAT	-0.026	0.18	-10000	0	-0.46	65	65
YBX1	0.039	0.042	-10000	0	-0.29	8	8
LCK	0.035	0.007	-10000	0	0	18	18
SHC1	0.033	0.011	-10000	0	0	52	52
NOX4	0.034	0.016	-10000	0	-10000	0	0

×

FoxO family 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
G6PC	0	0.048	-10000	0	-10000	0	0
PLK1	-0.06	0.2	-10000	0	-0.61	26	26
CDKN1B	-0.12	0.21	0.41	4	-0.36	148	152
FOXO3	-0.066	0.22	0.33	5	-0.48	85	90
KAT2B	-0.001	0.021	0.047	17	-0.041	80	97
FOXO1/SIRT1	0.013	0.051	-10000	0	-0.24	8	8
CAT	-0.076	0.26	-10000	0	-0.91	25	25
CTNNB1	0.036	0.006	-10000	0	0	15	15
AKT1	0.021	0.043	-10000	0	-0.063	55	55
FOXO1	0.003	0.053	0.22	1	-0.26	7	8
MAPK10	0.045	0.094	0.19	131	-0.15	19	150
mol:GTP	-0.001	0.004	-10000	0	-10000	0	0
FOXO4	-0.032	0.19	0.26	14	-0.45	60	74
response to oxidative stress	0	0.023	0.054	12	-0.049	36	48
FOXO3A/SIRT1	-0.062	0.22	0.3	5	-0.46	89	94
XPO1	0.036	0.004	-10000	0	0	5	5
EP300	0.034	0.011	-10000	0	-10000	0	0
BCL2L11	0.024	0.031	-10000	0	-10000	0	0
FOXO1/SKP2	0.019	0.056	-10000	0	-0.23	8	8
mol:GDP	0	0.023	0.054	12	-0.049	36	48
RAN	0.034	0.011	-10000	0	-0.015	20	20
GADD45A	-0.16	0.33	0.43	2	-0.82	78	80
YWHAQ	0.036	0.005	-10000	0	0	8	8
FOXO1/14-3-3 family	0.007	0.15	-10000	0	-0.52	21	21
MST1	0.022	0.043	0.11	1	-0.06	87	88
CSNK1D	0.035	0.007	-10000	0	0	20	20
CSNK1E	0.032	0.013	-10000	0	0	68	68
FOXO4/14-3-3 family	-0.004	0.15	-10000	0	-0.49	25	25
YWHAB	0.034	0.01	-10000	0	0	41	41
MAPK8	0.024	0.076	0.18	77	-0.14	12	89
MAPK9	0.053	0.097	0.19	154	-0.14	14	168
YWHAG	0	0	-10000	0	-10000	0	0
YWHAE	0.035	0.008	-10000	0	0	27	27
YWHAZ	0.035	0.007	-10000	0	0	21	21
SIRT1	0.019	0.023	-10000	0	-0.035	38	38
SOD2	-0.14	0.35	0.43	4	-0.79	94	98
RBL2	-0.072	0.28	-10000	0	-0.99	31	31
RAL/GDP	0.018	0.049	-10000	0	-0.14	19	19
CHUK	0.012	0.038	-10000	0	-0.059	74	74
Ran/GTP	0.018	0.025	-10000	0	-0.12	6	6
CSNK1G2	0.035	0.008	-10000	0	0	27	27
RAL/GTP	0.017	0.05	0.15	2	-0.12	19	21
CSNK1G1	0.036	0.005	-10000	0	0	11	11
FASLG	0.022	0.042	-10000	0	-0.59	1	1
SKP2	0.036	0.006	-10000	0	0	16	16
USP7	0.034	0.011	-10000	0	-0.012	23	23
IKBKB	0.023	0.044	0.11	1	-0.06	91	92
CCNB1	-0.17	0.42	0.5	1	-1.1	85	86
FOXO1-3a-4/beta catenin	-0.041	0.21	0.38	9	-0.4	79	88
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.055	0.2	1	-0.23	8	9
CSNK1A1	0.036	0.006	-10000	0	0	12	12
SGK1	-0.001	0.021	0.047	17	-0.041	80	97
CSNK1G3	0.036	0.005	-10000	0	0	11	11
Ran/GTP/Exportin 1	0.039	0.036	-10000	0	-0.16	6	6
ZFAND5	-0.019	0.16	0.25	14	-0.36	59	73
SFN	0.031	0.013	-10000	0	0	80	80
CDK2	0.036	0.012	-10000	0	-0.031	3	3
FOXO3A/14-3-3	-0.013	0.16	-10000	0	-0.48	30	30
CREBBP	0.038	0.008	-10000	0	-0.031	3	3
FBXO32	-0.06	0.2	0.3	6	-0.44	85	91
BCL6	-0.094	0.32	-10000	0	-0.98	47	47
RALB	0.033	0.014	-10000	0	-0.016	32	32
RALA	0.023	0.018	-10000	0	-0.001	186	186
YWHAH	0.031	0.013	-10000	0	0	73	73

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.009	0.12	0.26	3	-0.31	38	41
IKBKB	0.018	0.08	0.27	4	-0.26	10	14
AKT1	0.005	0.086	0.22	29	-0.18	18	47
IKBKG	0.01	0.072	0.25	1	-0.24	12	13
CALM1	-0.029	0.13	0.21	4	-0.36	46	50
PIK3CA	0.031	0.014	-10000	0	0	82	82
MAP3K1	0.021	0.13	0.29	7	-0.35	35	42
MAP3K7	0.034	0.01	-10000	0	0	43	43
mol:Ca2+	-0.026	0.14	0.22	6	-0.37	46	52
DOK1	0.037	0.002	-10000	0	0	2	2
AP-1	-0.018	0.096	0.19	10	-0.21	50	60
LYN	0.031	0.013	-10000	0	0	74	74
BLNK	0.019	0.018	-10000	0	0	248	248
SHC1	0.033	0.011	-10000	0	0	52	52
BCR complex	0.05	0.015	-10000	0	-10000	0	0
CD22	-0.016	0.093	-10000	0	-0.3	35	35
CAMK2G	-0.019	0.12	0.2	4	-0.34	45	49
CSNK2A1	0.033	0.011	-10000	0	0	51	51
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.035	0.057	-10000	0	-0.2	24	24
GO:0007205	-0.028	0.14	0.22	5	-0.38	47	52
SYK	0.031	0.013	-10000	0	0	74	74
ELK1	-0.033	0.13	0.21	5	-0.37	45	50
NFATC1	-0.023	0.093	0.26	3	-0.27	34	37
B-cell antigen/BCR complex	0.05	0.015	-10000	0	-10000	0	0
PAG1/CSK	0.024	0.023	-10000	0	-0.13	10	10
NFKBIB	0.021	0.042	0.16	1	-0.13	17	18
HRAS	-0.029	0.12	0.2	10	-0.32	48	58
NFKBIA	0.021	0.038	0.16	1	-0.12	13	14
NF-kappa-B/RelA/I kappa B beta	0.026	0.037	0.16	1	-0.11	14	15
RasGAP/Csk	0.044	0.098	-10000	0	-0.12	117	117
mol:GDP	-0.026	0.13	0.22	5	-0.36	46	51
PTEN	0.025	0.017	-10000	0	0	168	168
CD79B	0.036	0.005	-10000	0	0	11	11
NF-kappa-B/RelA/I kappa B alpha	0.026	0.036	0.16	1	-0.11	9	10
GRB2	0.035	0.007	-10000	0	0	18	18
PI3K/BCAP/CD19	-0.038	0.16	0.38	1	-0.43	48	49
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	-0.027	0.14	0.22	6	-0.38	45	51
CSK	0.035	0.007	-10000	0	0	18	18
FOS	-0.031	0.13	0.2	7	-0.35	49	56
CHUK	-0.06	0.14	0.25	1	-0.25	143	144
IBTK	0.035	0.008	-10000	0	0	28	28
CARD11/BCL10/MALT1/TAK1	-0.004	0.13	0.23	2	-0.34	41	43
PTPN6	-0.021	0.094	0.19	7	-0.3	34	41
RELA	0.036	0.004	-10000	0	0	7	7
BCL2A1	0.018	0.034	0.098	12	-0.095	17	29
VAV2	-0.016	0.11	-10000	0	-0.32	37	37
ubiquitin-dependent protein catabolic process	0.022	0.041	0.16	1	-0.13	17	18
BTK	0.018	0.012	-10000	0	-10000	0	0
CD19	-0.017	0.096	-10000	0	-0.29	39	39
MAP4K1	0.035	0.008	-10000	0	0	27	27
CD72	0.033	0.011	-10000	0	0	54	54
PAG1	0	0	-10000	0	-10000	0	0
MAPK14	0.017	0.12	0.27	7	-0.31	35	42
SH3BP5	0.033	0.011	-10000	0	0	52	52
PIK3AP1	-0.025	0.14	0.22	7	-0.36	57	64
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.036	0.18	-10000	0	-0.46	64	64
RAF1	-0.033	0.11	0.2	7	-0.31	49	56
RasGAP/p62DOK/SHIP	0.036	0.085	-10000	0	-0.11	114	114
CD79A	0.034	0.009	-10000	0	0	34	34
re-entry into mitotic cell cycle	-0.018	0.095	0.19	10	-0.21	50	60
RASA1	0.035	0.009	-10000	0	0	30	30
MAPK3	-0.039	0.099	0.19	4	-0.3	39	43
MAPK1	-0.038	0.1	0.19	6	-0.31	40	46
CD72/SHP1	-0.003	0.11	0.26	8	-0.29	37	45
NFKB1	0.035	0.007	-10000	0	0	18	18
MAPK8	0.017	0.12	0.27	7	-0.31	33	40
actin cytoskeleton organization	0.029	0.11	0.27	12	-0.3	22	34
NF-kappa-B/RelA	0.044	0.087	0.28	1	-0.25	19	20
Calcineurin	-0.01	0.13	0.23	1	-0.33	45	46
PI3K	-0.034	0.087	-10000	0	-0.27	36	36
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.02	0.14	0.23	6	-0.38	53	59
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	0.014	0.15	-10000	0	-0.61	10	10
DAPP1	-0.004	0.16	-10000	0	-0.72	9	9
cytokine secretion	-0.021	0.089	0.26	3	-0.26	34	37
mol:DAG	-0.027	0.14	0.22	6	-0.38	45	51
PLCG2	0.032	0.012	-10000	0	0	63	63
MAP2K1	-0.037	0.11	0.2	4	-0.31	46	50
B-cell antigen/BCR complex/FcgammaRIIB	0.015	0.075	-10000	0	-0.12	97	97
mol:PI-3-4-5-P3	-0.018	0.072	0.19	13	-0.22	19	32
ETS1	-0.03	0.11	0.2	3	-0.32	46	49
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.032	0.094	-10000	0	-0.16	61	61
B-cell antigen/BCR complex/LYN	-0.012	0.1	-10000	0	-0.3	40	40
MALT1	0.034	0.009	-10000	0	0	34	34
TRAF6	0.036	0.005	-10000	0	0	10	10
RAC1	0.027	0.12	0.27	11	-0.31	22	33
B-cell antigen/BCR complex/LYN/SYK	0.023	0.11	-10000	0	-0.28	34	34
CARD11	-0.027	0.13	0.21	5	-0.36	47	52
FCGR2B	0.02	0.018	-10000	0	0	226	226
PPP3CA	0.034	0.01	-10000	0	0	37	37
BCL10	0.035	0.007	-10000	0	0	19	19
IKK complex	0.004	0.044	0.13	5	-0.12	9	14
PTPRC	0.029	0.015	-10000	0	0	110	110
PDPK1	-0.016	0.056	0.16	14	-0.17	14	28
PPP3CB	0.025	0.017	-10000	0	0	158	158
PPP3CC	0.036	0.006	-10000	0	0	12	12
POU2F2	0.016	0.03	0.1	3	-0.085	18	21

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	-0.02	0.11	0.2	3	-0.36	31	34
adherens junction organization	0.002	0.077	0.16	3	-0.31	19	22
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.027	0.11	0.17	119	-0.28	22	141
FMN1	0.01	0.066	0.16	3	-0.27	16	19
mol:IP3	-0.007	0.079	0.14	5	-0.26	29	34
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.015	0.068	0.16	3	-0.28	15	18
CTNNB1	0.035	0.006	-10000	0	0	15	15
AKT1	-0.002	0.09	0.14	6	-0.33	24	30
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.031	0.069	-10000	0	-0.49	4	4
CTNND1	0.035	0.009	-10000	0	0	31	31
mol:PI-4-5-P2	0.005	0.068	0.16	4	-0.27	18	22
VASP	0.004	0.065	0.15	3	-0.28	16	19
ZYX	0.008	0.054	0.15	4	-0.31	8	12
JUB	0.01	0.066	0.16	3	-0.27	16	19
EGFR(dimer)	0.001	0.062	-10000	0	-0.3	14	14
E-cadherin/beta catenin-gamma catenin	0.064	0.029	-10000	0	-0.12	3	3
mol:PI-3-4-5-P3	0.024	0.096	0.2	3	-0.3	22	25
PIK3CA	0.03	0.016	-10000	0	-0.003	89	89
PI3K	0.025	0.098	0.21	3	-0.31	22	25
FYN	-0.039	0.13	0.25	1	-0.32	72	73
mol:Ca2+	-0.007	0.077	0.14	5	-0.26	29	34
JUP	0.033	0.011	0.056	1	0	51	52
PIK3R1	0.032	0.015	-10000	0	-0.003	70	70
mol:DAG	-0.007	0.079	0.14	5	-0.26	29	34
CDH1	0.034	0.01	-10000	0	0	37	37
RhoA/GDP	0.056	0.12	0.18	205	-0.29	22	227
establishment of polarity of embryonic epithelium	0.003	0.065	0.15	3	-0.27	17	20
SRC	0.034	0.009	-10000	0	0	34	34
RAC1	0.025	0.017	-10000	0	0	163	163
RHOA	0.035	0.007	-10000	0	0	21	21
EGFR	0.009	0.016	-10000	0	0	379	379
CASR	-0.023	0.076	0.14	20	-0.28	23	43
RhoA/GTP	0.01	0.086	0.16	1	-0.27	25	26
AKT2	-0.002	0.082	0.14	5	-0.29	23	28
actin cable formation	0.001	0.063	0.15	3	-0.27	17	20
apoptosis	0.007	0.099	0.34	27	-0.17	13	40
CTNNA1	0.036	0.008	-10000	0	-0.002	19	19
mol:GDP	-0.021	0.072	0.19	4	-0.3	21	25
PIP5K1A	0.005	0.068	0.18	2	-0.28	17	19
PLCG1	-0.008	0.081	0.14	5	-0.27	29	34
Rac1/GTP	-0.003	0.066	-10000	0	-0.28	14	14
homophilic cell adhesion	-0.001	0.004	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.03	0.17	-10000	0	-0.47	63	63
HDAC1	0.027	0.034	0.08	55	-0.039	84	139
AES	0.034	0.013	0.069	11	-0.004	43	54
FBXW11	0.035	0.007	-10000	0	0	22	22
DTX1	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.033	0.027	-10000	0	-10000	0	0
TLE1	0.034	0.013	0.07	9	-0.008	32	41
AP1	-0.012	0.078	-10000	0	-0.21	59	59
NCSTN	0.035	0.009	-10000	0	0	29	29
ADAM10	0.033	0.012	-10000	0	0	56	56
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.01	0.13	-10000	0	-0.48	15	15
NICD/RBPSUH	-0.033	0.17	-10000	0	-0.47	63	63
WIF1	0.029	0.015	-10000	0	0	112	112
NOTCH1	-0.029	0.18	-10000	0	-0.5	62	62
PSENEN	0.034	0.009	-10000	0	0	31	31
KREMEN2	0.036	0.005	-10000	0	0	9	9
DKK1	0.017	0.018	-10000	0	0	277	277
beta catenin/beta TrCP1	0.064	0.093	0.24	22	-0.31	8	30
APH1B	0.036	0.006	-10000	0	0	14	14
APH1A	0.036	0.006	-10000	0	0	12	12
AXIN1	0.014	0.065	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.012	0.072	0.17	49	-0.2	11	60
PSEN1	0.033	0.011	-10000	0	0	47	47
FOS	0.025	0.017	-10000	0	0	162	162
JUN	0.034	0.01	-10000	0	0	41	41
MAP3K7	0.032	0.018	0.063	8	-0.011	63	71
CTNNB1	0.051	0.09	0.22	38	-0.3	6	44
MAPK3	0.036	0.003	-10000	0	0	4	4
DKK2/LRP6/Kremen 2	0.064	0.027	-10000	0	-0.13	1	1
HNF1A	0	0.006	0.033	10	-10000	0	10
CTBP1	0.034	0.013	0.07	9	-0.007	35	44
MYC	-0.082	0.37	-10000	0	-1.2	52	52
NKD1	0	0.003	-10000	0	-10000	0	0
FZD1	0.024	0.017	-10000	0	0	175	175
NOTCH1 precursor/Deltex homolog 1	-0.033	0.17	-10000	0	-0.47	63	63
apoptosis	-0.013	0.078	-10000	0	-0.21	60	60
Delta 1/NOTCHprecursor	-0.033	0.17	-10000	0	-0.47	63	63
DLL1	0	0	-10000	0	-10000	0	0
PPARD	0.025	0.037	-10000	0	-10000	0	0
Gamma Secretase	0.08	0.072	-10000	0	-0.16	28	28
APC	-0.02	0.17	-10000	0	-0.65	28	28
DVL1	0.019	0.087	-10000	0	-0.41	15	15
CSNK2A1	0.033	0.011	-10000	0	0	51	51
MAP3K7IP1	0.032	0.018	0.063	8	-0.012	56	64
DKK1/LRP6/Kremen 2	0.03	0.037	-10000	0	-10000	0	0
LRP6	0.034	0.01	-10000	0	0	40	40
CSNK1A1	0.036	0.006	-10000	0	0	12	12
NLK	0.01	0.053	0.14	1	-0.21	22	23
CCND1	-0.047	0.34	-10000	0	-1.2	42	42
WNT1	0.035	0.007	-10000	0	0	18	18
Axin1/APC/beta catenin	0.016	0.13	0.29	1	-0.43	28	29
DKK2	0.035	0.009	-10000	0	0	31	31
NOTCH1 precursor/DVL1	-0.004	0.19	-10000	0	-0.5	52	52
GSK3B	0.034	0.01	-10000	0	0	39	39
FRAT1	0.025	0.017	-10000	0	0	163	163
NOTCH/Deltex homolog 1	-0.03	0.17	-10000	0	-0.47	63	63
PPP2R5D	0.026	0.037	-10000	0	-0.25	4	4
MAPK1	0.034	0.01	-10000	0	0	44	44
WNT1/LRP6/FZD1	0.057	0.046	-10000	0	-10000	0	0
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.032	0.021	0.07	5	-0.019	63	68

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.028	0.015	-10000	0	0	115	115
EPHB2	0.034	0.01	-10000	0	0	40	40
EFNB1	-0.017	0.02	0.092	7	-10000	0	7
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.049	0.054	-10000	0	-0.15	8	8
Ephrin B2/EPHB1-2	0.032	0.057	-10000	0	-0.11	52	52
neuron projection morphogenesis	0.034	0.041	-10000	0	-0.13	11	11
Ephrin B1/EPHB1-2/Tiam1	0.058	0.049	-10000	0	-0.1	28	28
DNM1	0.035	0.008	-10000	0	0	26	26
cell-cell signaling	0	0.003	0.023	1	-10000	0	1
MAP2K4	-0.054	0.16	-10000	0	-0.52	52	52
YES1	-0.054	0.24	-10000	0	-0.75	52	52
Ephrin B1/EPHB1-2/NCK2	0.062	0.044	-10000	0	-0.1	20	20
PI3K	-0.019	0.19	-10000	0	-0.56	51	51
mol:GDP	0.056	0.048	-10000	0	-0.1	28	28
ITGA2B	0.037	0.003	-10000	0	0	3	3
endothelial cell proliferation	0.016	0.047	-10000	0	-0.12	45	45
FYN	-0.065	0.24	-10000	0	-0.77	52	52
MAP3K7	-0.051	0.16	-10000	0	-0.54	51	51
FGR	-0.051	0.23	-10000	0	-0.72	51	51
TIAM1	0.033	0.011	-10000	0	0	46	46
PIK3R1	0.032	0.012	-10000	0	0	63	63
RGS3	0.035	0.007	-10000	0	0	22	22
cell adhesion	-0.031	0.17	-10000	0	-0.53	51	51
LYN	-0.061	0.23	-10000	0	-0.74	52	52
Ephrin B1/EPHB1-2/Src Family Kinases	-0.057	0.21	-10000	0	-0.68	52	52
Ephrin B1/EPHB1-2	-0.047	0.18	-10000	0	-0.57	51	51
SRC	-0.05	0.23	-10000	0	-0.72	52	52
ITGB3	0.036	0.003	-10000	0	0	4	4
EPHB1	0.03	0.015	-10000	0	0	94	94
EPHB4	0.025	0.017	-10000	0	0	164	164
RAC1	0.025	0.017	-10000	0	0	163	163
Ephrin B2/EPHB4	0.016	0.047	-10000	0	-0.12	45	45
alphaIIb/beta3 Integrin	0.054	0.005	-10000	0	-10000	0	0
BLK	-0.052	0.23	-10000	0	-0.72	52	52
HCK	-0.065	0.23	-10000	0	-0.74	52	52
regulation of stress fiber formation	-0.06	0.043	0.1	20	-10000	0	20
MAPK8	-0.056	0.15	-10000	0	-0.5	52	52
Ephrin B1/EPHB1-2/RGS3	0.068	0.034	-10000	0	-0.11	6	6
endothelial cell migration	0.006	0.17	0.22	39	-0.45	44	83
NCK2	0.036	0.007	-10000	0	0	17	17
PTPN13	0.034	0.014	-10000	0	0	60	60
regulation of focal adhesion formation	-0.06	0.043	0.1	20	-10000	0	20
chemotaxis	-0.065	0.033	0.11	6	-10000	0	6
PIK3CA	0.031	0.014	-10000	0	0	82	82
Rac1/GTP	0.042	0.048	-10000	0	-0.14	9	9
angiogenesis	-0.048	0.18	-10000	0	-0.57	52	52
LCK	-0.05	0.22	-10000	0	-0.72	51	51

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.01	0.098	0.33	2	-0.41	4	6
UGCG	-0.026	0.19	-10000	0	-0.74	30	30
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.007	0.13	0.26	10	-0.34	39	49
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.024	0.18	-10000	0	-0.73	30	30
mol:DAG	-0.007	0.031	0.17	15	-10000	0	15
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.026	0.18	0.29	8	-0.42	63	71
FRAP1	-0.035	0.2	0.31	9	-0.47	63	72
FOXO3	-0.035	0.2	0.29	11	-0.46	67	78
AKT1	-0.04	0.21	0.32	7	-0.49	68	75
GAB2	0.03	0.019	-10000	0	-0.012	81	81
SMPD1	0.002	0.096	-10000	0	-0.52	14	14
SGMS1	-0.003	0.034	0.066	19	-0.072	67	86
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	-0.028	0.046	0.077	7	-0.13	72	79
CALM1	0.033	0.012	-10000	0	0	57	57
cell proliferation	-0.032	0.19	0.28	11	-0.38	74	85
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	0.017	0.078	-10000	0	-0.16	72	72
RPS6KB1	0.029	0.028	-10000	0	-10000	0	0
mol:sphingomyelin	-0.007	0.031	0.17	15	-10000	0	15
natural killer cell activation	0	0.004	0.007	28	-0.01	47	75
JAK3	0.034	0.017	-10000	0	-0.028	25	25
PIK3R1	0.031	0.02	-10000	0	-0.029	26	26
JAK1	0.032	0.019	-10000	0	-0.028	30	30
NFKB1	0.035	0.007	-10000	0	0	18	18
MYC	-0.069	0.3	0.42	10	-0.81	61	71
MYB	0.033	0.042	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.025	0.16	0.27	7	-0.4	49	56
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.038	0.032	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.023	0.16	0.28	8	-0.39	49	57
Rac1/GDP	0.005	0.05	0.12	6	-0.13	44	50
T cell proliferation	-0.024	0.15	0.26	8	-0.36	49	57
SHC1	0.029	0.019	-10000	0	-0.011	85	85
RAC1	0.025	0.017	-10000	0	0	163	163
positive regulation of cyclin-dependent protein kinase activity	0.005	0.012	0.058	24	-10000	0	24
PRKCZ	-0.025	0.16	0.26	8	-0.38	49	57
NF kappa B1 p50/RelA	-0.013	0.19	0.31	8	-0.42	63	71
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.006	0.094	0.21	3	-0.29	26	29
HSP90AA1	0	0	-10000	0	-10000	0	0
RELA	0.036	0.004	-10000	0	0	7	7
IL2RA	0.021	0.021	-10000	0	-0.004	205	205
IL2RB	0.032	0.019	-10000	0	-0.028	25	25
TERT	0.036	0.006	-10000	0	0	15	15
E2F1	0.035	0.032	-10000	0	-10000	0	0
SOS1	0	0.003	0.007	36	-0.009	47	83
RPS6	0.031	0.014	-10000	0	0	86	86
mol:cAMP	-0.003	0.007	-10000	0	-0.032	25	25
PTPN11	0.032	0.018	-10000	0	-0.023	48	48
IL2RG	0.034	0.017	-10000	0	-0.03	26	26
actin cytoskeleton organization	-0.024	0.15	0.26	8	-0.36	49	57
GRB2	0.033	0.017	-10000	0	-0.018	46	46
IL2	0.035	0.017	-10000	0	-0.03	26	26
PIK3CA	0.029	0.02	-10000	0	-0.029	27	27
Rac1/GTP	0.028	0.064	0.16	5	-0.12	44	49
LCK	0.034	0.017	-10000	0	-0.03	26	26
BCL2	-0.022	0.16	0.32	2	-0.44	34	36

×

EPHB forward signaling

Figure S42. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S42. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.045	0.014	-10000	0	-10000	0	0
cell-cell adhesion	0.031	0.041	0.15	36	-10000	0	36
Ephrin B/EPHB2/RasGAP	0.06	0.091	-10000	0	-0.14	75	75
ITSN1	0.035	0.007	-10000	0	0	21	21
PIK3CA	0.031	0.014	-10000	0	0	82	82
SHC1	0.033	0.011	-10000	0	0	52	52
Ephrin B1/EPHB3	0.045	0.015	-10000	0	-10000	0	0
Ephrin B1/EPHB1	0.039	0.025	-10000	0	-0.12	6	6
HRAS/GDP	0.003	0.084	0.17	1	-0.22	41	42
Ephrin B/EPHB1/GRB7	0.068	0.076	-10000	0	-0.12	47	47
Endophilin/SYNJ1	-0.028	0.055	0.19	12	-0.19	2	14
KRAS	0.034	0.009	-10000	0	0	34	34
Ephrin B/EPHB1/Src	0.063	0.077	-10000	0	-0.12	52	52
endothelial cell migration	0.02	0.073	-10000	0	-0.14	65	65
GRB2	0.035	0.007	-10000	0	0	18	18
GRB7	0.036	0.006	-10000	0	0	15	15
PAK1	-0.03	0.059	0.19	16	-10000	0	16
HRAS	0.034	0.009	-10000	0	0	36	36
RRAS	-0.027	0.055	0.21	8	-0.19	10	18
DNM1	0.035	0.008	-10000	0	0	26	26
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.02	0.065	0.18	18	-0.19	11	29
lamellipodium assembly	-0.031	0.041	-10000	0	-0.15	36	36
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.01	0.075	-10000	0	-0.28	16	16
PIK3R1	0.032	0.012	-10000	0	0	63	63
EPHB2	0.034	0.01	-10000	0	0	40	40
EPHB3	0.033	0.011	-10000	0	0	52	52
EPHB1	0.03	0.014	-10000	0	0	94	94
EPHB4	0.025	0.017	-10000	0	0	164	164
mol:GDP	0.017	0.12	0.2	101	-0.24	35	136
Ephrin B/EPHB2	0.052	0.069	-10000	0	-0.11	65	65
Ephrin B/EPHB3	0.051	0.069	-10000	0	-0.11	64	64
JNK cascade	-0.007	0.067	0.23	19	-0.2	4	23
Ephrin B/EPHB1	0.052	0.066	-10000	0	-0.11	54	54
RAP1/GDP	0.026	0.12	0.2	105	-0.23	36	141
EFNB2	0.028	0.015	-10000	0	0	115	115
EFNB3	0.035	0.009	-10000	0	0	29	29
EFNB1	0.037	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.031	0.059	-10000	0	-0.11	52	52
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.036	0.005	-10000	0	0	10	10
CDC42/GTP	0.044	0.084	-10000	0	-0.19	34	34
Rap1/GTP	-0.045	0.053	0.053	9	-0.21	22	31
axon guidance	0.045	0.014	-10000	0	-10000	0	0
MAPK3	-0.007	0.072	0.16	3	-0.28	16	19
MAPK1	-0.007	0.075	0.17	2	-0.28	20	22
Rac1/GDP	-0.01	0.094	0.24	21	-0.24	34	55
actin cytoskeleton reorganization	-0.041	0.061	-10000	0	-0.2	44	44
CDC42/GDP	0.033	0.13	0.22	108	-0.24	35	143
PI3K	0.024	0.077	-10000	0	-0.14	65	65
EFNA5	0.036	0.004	-10000	0	0	5	5
Ephrin B2/EPHB4	0.016	0.048	-10000	0	-0.12	45	45
Ephrin B/EPHB2/Intersectin/N-WASP	0.001	0.063	-10000	0	-0.17	45	45
CDC42	0.035	0.008	-10000	0	0	26	26
RAS family/GTP	-0.053	0.062	0.05	32	-0.24	24	56
PTK2	-0.014	0.084	0.53	10	-10000	0	10
MAP4K4	-0.007	0.067	0.23	19	-0.2	4	23
SRC	0.034	0.009	-10000	0	0	34	34
KALRN	0.035	0.007	-10000	0	0	22	22
Intersectin/N-WASP	0.033	0.034	-10000	0	-0.14	8	8
neuron projection morphogenesis	0.058	0.17	0.33	121	-0.23	14	135
MAP2K1	0.001	0.073	-10000	0	-0.27	18	18
WASL	0.025	0.017	-10000	0	0	167	167
Ephrin B1/EPHB1-2/NCK1	0.082	0.039	-10000	0	-0.12	10	10
cell migration	-0.012	0.087	0.22	1	-0.29	20	21
NRAS	0.032	0.012	-10000	0	0	63	63
SYNJ1	-0.028	0.056	0.2	12	-0.19	2	14
PXN	0.036	0.004	-10000	0	0	7	7
TF	-0.023	0.051	0.2	5	-0.19	21	26
HRAS/GTP	0.034	0.08	-10000	0	-0.15	61	61
Ephrin B1/EPHB1-2	0.053	0.035	-10000	0	-0.11	6	6
cell adhesion mediated by integrin	0.019	0.046	0.15	6	-0.24	5	11
RAC1	0.025	0.017	-10000	0	0	163	163
mol:GTP	0.042	0.078	-10000	0	-0.14	62	62
RAC1-CDC42/GTP	-0.031	0.047	-10000	0	-0.2	13	13
RASA1	0.035	0.009	-10000	0	0	30	30
RAC1-CDC42/GDP	0.01	0.096	0.25	18	-0.24	33	51
ruffle organization	0.067	0.17	0.31	138	-0.22	16	154
NCK1	0.035	0.008	-10000	0	0	27	27
receptor internalization	-0.033	0.052	0.18	12	-0.19	2	14
Ephrin B/EPHB2/KALRN	0.066	0.08	-10000	0	-0.12	62	62
ROCK1	-0.009	0.045	0.12	47	-10000	0	47
RAS family/GDP	-0.043	0.064	-10000	0	-0.21	44	44
Rac1/GTP	-0.029	0.046	-10000	0	-0.2	13	13
Ephrin B/EPHB1/Src/Paxillin	0.009	0.064	-10000	0	-0.21	7	7

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.042	0.011	-10000	0	-0.042	1	1
NFATC2	0.015	0.16	0.28	6	-0.33	51	57
NFATC3	0.018	0.13	0.27	25	-0.24	73	98
CD40LG	-0.018	0.34	0.49	44	-0.69	72	116
ITCH	0.033	0.047	0.19	8	-10000	0	8
CBLB	0.036	0.049	0.2	11	-10000	0	11
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.054	0.26	0.38	13	-0.6	61	74
JUNB	0.031	0.014	-10000	0	0	84	84
CaM/Ca2+/Calcineurin A alpha-beta B1	0.033	0.029	-10000	0	-0.14	7	7
T cell anergy	0.016	0.068	0.22	19	-0.24	1	20
TLE4	0.01	0.11	-10000	0	-0.31	22	22
Jun/NFAT1-c-4/p21SNFT	-0.018	0.33	0.45	2	-0.73	72	74
AP-1/NFAT1-c-4	-0.035	0.35	-10000	0	-0.78	68	68
IKZF1	0.006	0.1	0.17	13	-0.22	49	62
T-helper 2 cell differentiation	-0.088	0.23	-10000	0	-0.64	41	41
AP-1/NFAT1	0.017	0.15	0.28	18	-0.29	49	67
CALM1	0.046	0.024	0.14	2	-10000	0	2
EGR2	-0.077	0.42	0.5	14	-0.97	76	90
EGR3	-0.055	0.42	0.49	20	-0.98	72	92
NFAT1/FOXP3	0.039	0.12	0.25	4	-0.25	39	43
EGR1	0.029	0.015	0.071	1	0	107	108
JUN	0.032	0.042	0.11	34	-0.055	8	42
EGR4	0.037	0.004	0.071	1	0	5	6
mol:Ca2+	0.005	0.003	-10000	0	-10000	0	0
GBP3	0.006	0.1	0.17	13	-0.22	49	62
FOSL1	0.033	0.011	-10000	0	0	53	53
NFAT1-c-4/MAF/IRF4	0.009	0.33	-10000	0	-0.72	75	75
DGKA	0.011	0.1	0.21	1	-0.27	30	31
CREM	0.026	0.016	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.006	0.33	-10000	0	-0.73	74	74
CTLA4	0.009	0.093	0.18	1	-0.23	30	31
NFAT1-c-4 (dimer)/EGR1	-0.029	0.34	-10000	0	-0.76	76	76
NFAT1-c-4 (dimer)/EGR4	0.001	0.34	-10000	0	-0.74	74	74
FOS	0.023	0.038	0.11	19	-0.051	7	26
IFNG	-0.01	0.13	-10000	0	-0.4	21	21
T cell activation	-0.014	0.22	-10000	0	-0.56	31	31
MAF	0.035	0.009	-10000	0	0	34	34
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.006	0.28	0.6	73	-0.46	21	94
TNF	-0.041	0.31	0.4	12	-0.7	76	88
FASLG	-0.1	0.46	-10000	0	-1.1	75	75
TBX21	0.04	0.006	0.11	3	-10000	0	3
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	0.026	0.018	-10000	0	-10000	0	0
PTPN1	0.007	0.12	0.43	2	-0.32	32	34
NFAT1-c-4/ICER1	-0.033	0.32	-10000	0	-0.73	74	74
GATA3	0.027	0.018	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.004	0.14	-10000	0	-0.4	21	21
IL2RA	-0.064	0.25	0.34	2	-0.57	72	74
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.008	0.11	-10000	0	-0.33	28	28
E2F1	0.036	0.051	0.11	2	-0.25	12	14
PPARG	0.035	0.008	-10000	0	-10000	0	0
SLC3A2	0.006	0.12	0.24	2	-0.36	31	33
IRF4	0.037	0.002	-10000	0	0	1	1
PTGS2	-0.074	0.28	0.44	3	-0.69	68	71
CSF2	-0.019	0.34	0.49	44	-0.69	72	116
JunB/Fra1/NFAT1-c-4	-0.014	0.31	-10000	0	-0.71	72	72
IL4	-0.091	0.24	-10000	0	-0.67	40	40
IL5	-0.019	0.34	0.49	44	-0.69	72	116
IL2	-0.015	0.22	-10000	0	-0.57	30	30
IL3	0.009	0.082	-10000	0	-0.6	5	5
RNF128	0.014	0.023	0.17	1	-10000	0	1
NFATC1	-0.006	0.28	0.46	21	-0.6	73	94
CDK4	-0.01	0.27	0.52	37	-1	14	51
PTPRK	-0.003	0.14	-10000	0	-0.42	39	39
IL8	-0.1	0.3	0.46	7	-0.74	68	75
POU2F1	0.039	0.008	-10000	0	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.019	0.038	-10000	0	-0.055	95	95
HSPA8	0.036	0.009	-10000	0	0	25	25
SMAD3/SMAD4/ER alpha	0.043	0.088	0.23	10	-0.14	39	49
AKT1	0.03	0.02	-10000	0	-0.029	34	34
GSC	0.001	0.028	0.1	12	-0.065	3	15
NKX2-5	0.034	0.017	0.071	9	-0.061	12	21
muscle cell differentiation	-0.017	0.13	0.31	52	-10000	0	52
SMAD2-3/SMAD4/SP1	0.051	0.14	0.34	5	-0.24	50	55
SMAD4	0.021	0.057	0.14	4	-0.13	36	40
CBFB	0.036	0.006	-10000	0	0	14	14
SAP18	0.034	0.01	-10000	0	0	43	43
Cbp/p300/MSG1	0.01	0.088	-10000	0	-0.14	97	97
SMAD3/SMAD4/VDR	0.044	0.12	-10000	0	-0.2	36	36
MYC	0.029	0.014	-10000	0	-10000	0	0
CDKN2B	-0.21	0.19	-10000	0	-0.53	30	30
AP1	-0.004	0.1	0.21	2	-0.24	53	55
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	-0.012	0.13	-10000	0	-0.37	38	38
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.002	0.083	-10000	0	-0.28	31	31
SP3	0.035	0.016	0.081	11	-0.055	10	21
CREB1	0.036	0.004	-10000	0	0	7	7
FOXH1	0.035	0.016	0.072	10	-0.061	12	22
SMAD3/SMAD4/GR	0.04	0.093	0.24	2	-0.16	46	48
GATA3	0.027	0.018	-10000	0	-10000	0	0
SKI/SIN3/HDAC complex/NCoR1	-0.004	0.094	-10000	0	-0.3	28	28
MEF2C/TIF2	-0.02	0.074	0.28	8	-0.22	18	26
endothelial cell migration	0.2	0.5	1.2	106	-10000	0	106
MAX	0.027	0.043	0.084	90	-0.054	89	179
RBBP7	0.037	0.005	-10000	0	0	8	8
RBBP4	0.033	0.012	-10000	0	0	57	57
RUNX2	0.037	0.002	-10000	0	0	1	1
RUNX3	0.034	0.009	-10000	0	0	34	34
RUNX1	0.036	0.005	-10000	0	0	10	10
CTBP1	0.035	0.008	-10000	0	0	27	27
NR3C1	0.027	0.043	0.085	88	-0.054	90	178
VDR	0.035	0.007	-10000	0	0	21	21
CDKN1A	-0.11	0.36	0.4	1	-1.1	59	60
KAT2B	-0.003	0.008	-10000	0	-0.023	17	17
SMAD2/SMAD2/SMAD4/FOXH1	0.048	0.078	0.2	2	-0.16	39	41
DCP1A	0.035	0.008	-10000	0	0	24	24
SKI	0.037	0.001	-10000	0	-10000	0	0
SERPINE1	-0.2	0.5	-10000	0	-1.2	106	106
SMAD3/SMAD4/ATF2	0.04	0.088	0.21	1	-0.15	55	56
SMAD3/SMAD4/ATF3	0.019	0.1	-10000	0	-0.17	87	87
SAP30	0.036	0.007	-10000	0	0	18	18
Cbp/p300/PIAS3	0.041	0.074	-10000	0	-0.095	91	91
JUN	-0.015	0.1	0.19	9	-0.25	49	58
SMAD3/SMAD4/IRF7	0.043	0.092	-10000	0	-0.16	49	49
TFE3	0.016	0.06	0.11	8	-0.096	103	111
COL1A2	-0.041	0.21	-10000	0	-0.63	52	52
mesenchymal cell differentiation	-0.04	0.088	0.15	54	-0.21	1	55
DLX1	0	0	-10000	0	-10000	0	0
TCF3	0.035	0.008	-10000	0	0	26	26
FOS	0.02	0.03	0.12	2	-0.046	46	48
SMAD3/SMAD4/Max	0.04	0.089	0.24	2	-0.16	30	32
Cbp/p300/SNIP1	0.043	0.056	-10000	0	-0.13	8	8
ZBTB17	0.035	0.006	-10000	0	-10000	0	0
LAMC1	-0.035	0.1	0.16	5	-0.31	41	46
TGIF2/HDAC complex/SMAD3/SMAD4	0.037	0.086	0.21	1	-0.15	50	51
IRF7	0.034	0.01	-10000	0	-10000	0	0
ESR1	0.037	0.04	0.12	67	-0.026	61	128
HNF4A	0.034	0.01	-10000	0	0	37	37
MEF2C	-0.028	0.069	0.28	8	-0.23	20	28
SMAD2-3/SMAD4	0.041	0.097	0.23	2	-0.19	38	40
Cbp/p300/Src-1	0.031	0.076	-10000	0	-0.13	51	51
IGHV3OR16-13	0.005	0.057	-10000	0	-0.49	6	6
TGIF2/HDAC complex	0.034	0.01	-10000	0	0	44	44
CREBBP	0.022	0.034	-10000	0	-0.045	102	102
SKIL	0.036	0.006	-10000	0	0	13	13
HDAC1	0.036	0.008	-10000	0	0	21	21
HDAC2	0.033	0.012	-10000	0	0	59	59
SNIP1	0.036	0.007	-10000	0	0	15	15
GCN5L2	0.021	0.034	-10000	0	-0.04	116	116
SMAD3/SMAD4/TFE3	0.03	0.13	0.27	5	-0.23	57	62
MSG1/HSC70	0.008	0.081	-10000	0	-0.15	102	102
SMAD2	0.035	0.017	0.091	2	-0.049	11	13
SMAD3	0.018	0.06	0.14	3	-0.12	43	46
SMAD3/E2F4-5/DP1/p107/SMAD4	0.002	0.075	-10000	0	-0.18	48	48
SMAD2/SMAD2/SMAD4	-0.013	0.072	0.18	8	-0.2	43	51
NCOR1	0.035	0.008	-10000	0	0	27	27
NCOA2	0.036	0.006	-10000	0	0	12	12
NCOA1	0.033	0.011	-10000	0	0	49	49
MYOD/E2A	0.051	0.013	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.06	0.15	0.34	5	-0.24	47	52
IFNB1	-0.006	0.059	0.17	6	-0.18	10	16
SMAD3/SMAD4/MEF2C	0.026	0.095	0.26	4	-0.23	24	28
CITED1	0.026	0.017	-10000	0	0	153	153
SMAD2-3/SMAD4/ARC105	0.041	0.088	0.22	3	-0.17	34	37
RBL1	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.005	0.1	-10000	0	-0.34	29	29
RUNX1-3/PEBPB2	0.067	0.023	-10000	0	-10000	0	0
SMAD7	-0.041	0.18	0.28	3	-0.44	59	62
MYC/MIZ-1	0.027	0.059	-10000	0	-0.15	49	49
SMAD3/SMAD4	-0.081	0.24	0.22	3	-0.47	115	118
IL10	-0.008	0.063	0.19	8	-0.2	4	12
PIASy/HDAC complex	0.028	0.031	0.071	9	-0.031	89	98
PIAS3	0.023	0.029	-10000	0	-0.031	109	109
CDK2	0.021	0.032	-10000	0	-0.043	91	91
IL5	-0.01	0.065	0.19	9	-0.2	4	13
CDK4	0.021	0.031	-10000	0	-0.046	73	73
PIAS4	0.028	0.031	0.071	9	-0.031	89	98
ATF3	0.028	0.016	-10000	0	0	128	128
SMAD3/SMAD4/SP1	0.031	0.14	0.26	13	-0.23	67	80
FOXG1	0.001	0.007	0.023	23	-10000	0	23
FOXO3	-0.008	0.008	-10000	0	-10000	0	0
FOXO1	-0.008	0.007	-10000	0	-10000	0	0
FOXO4	-0.008	0.007	-10000	0	-10000	0	0
heart looping	-0.028	0.069	0.28	8	-0.23	20	28
CEBPB	0.032	0.014	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.024	0.075	0.18	2	-0.14	56	58
MYOD1	0.036	0.004	-10000	0	0	7	7
SMAD3/SMAD4/HNF4	0.037	0.087	0.21	1	-0.15	54	55
SMAD3/SMAD4/GATA3	0.032	0.087	-10000	0	-0.17	27	27
SnoN/SIN3/HDAC complex/NCoR1	0.036	0.006	-10000	0	0	13	13
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.069	0.095	-10000	0	-0.15	23	23
SMAD3/SMAD4/SP1-3	0.048	0.14	0.34	3	-0.24	50	53
MED15	0	0	-10000	0	-10000	0	0
SP1	0.015	0.075	0.12	18	-0.12	105	123
SIN3B	0.035	0.009	-10000	0	0	33	33
SIN3A	0	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.07	0.086	0.24	2	-0.16	39	41
ITGB5	-0.032	0.1	0.21	6	-0.26	37	43
TGIF/SIN3/HDAC complex/CtBP	-0.01	0.099	-10000	0	-0.32	31	31
SMAD3/SMAD4/AR	0.04	0.088	0.21	1	-0.15	51	52
AR	0.035	0.007	-10000	0	0	22	22
negative regulation of cell growth	-0.016	0.12	-10000	0	-0.3	57	57
SMAD3/SMAD4/MYOD	0.04	0.088	0.21	1	-0.15	52	53
E2F5	0.036	0.005	-10000	0	0	8	8
E2F4	0.036	0.005	-10000	0	0	10	10
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.061	0.099	0.24	1	-0.16	45	46
SMAD2-3/SMAD4/FOXO1-3a-4	-0.006	0.099	-10000	0	-0.31	32	32
TFDP1	0.033	0.011	-10000	0	0	53	53
SMAD3/SMAD4/AP1	0.022	0.12	0.25	3	-0.24	53	56
SMAD3/SMAD4/RUNX2	0.04	0.089	0.21	1	-0.15	54	55
TGIF2	0.034	0.01	-10000	0	0	44	44
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	0.036	0.005	-10000	0	0	11	11

×

Noncanonical Wnt signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0	0	-10000	0	-10000	0	0
GNB1/GNG2	0.003	0.1	-10000	0	-0.26	27	27
mol:DAG	-0.012	0.089	0.18	5	-0.25	26	31
PLCG1	-0.013	0.091	0.18	5	-0.26	26	31
YES1	-0.017	0.086	0.14	2	-0.18	86	88
FZD3	0.029	0.015	-10000	0	0	109	109
FZD6	0.027	0.016	-10000	0	0	130	130
G protein	0.002	0.11	0.21	24	-0.28	26	50
MAP3K7	-0.035	0.075	0.14	7	-0.23	32	39
mol:Ca2+	-0.012	0.087	0.17	5	-0.24	26	31
mol:IP3	-0.012	0.089	0.18	5	-0.25	26	31
NLK	-0.037	0.25	-10000	0	-0.77	52	52
GNB1	0.035	0.007	-10000	0	0	20	20
CAMK2A	-0.03	0.078	0.16	6	-0.24	26	32
MAP3K7IP1	0.034	0.009	-10000	0	0	36	36
Noncanonical Wnts/FZD	-0.006	0.089	-10000	0	-0.17	89	89
CSNK1A1	0.036	0.006	-10000	0	0	12	12
GNAS	-0.016	0.081	0.14	2	-0.17	84	86
GO:0007205	-0.019	0.084	0.17	5	-0.26	26	31
WNT6	0.037	0.002	-10000	0	0	1	1
WNT4	0.035	0.007	-10000	0	0	20	20
NFAT1/CK1 alpha	-0.005	0.099	0.22	5	-0.27	27	32
GNG2	0	0	-10000	0	-10000	0	0
WNT5A	0.03	0.015	-10000	0	0	99	99
WNT11	0.036	0.006	-10000	0	0	15	15
CDC42	-0.026	0.084	0.17	5	-0.27	23	28

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.017	0.2	-10000	0	-0.82	26	26
regulation of axonogenesis	0.004	0.066	0.21	39	-10000	0	39
myoblast fusion	-0.014	0.094	0.35	28	-0.17	2	30
mol:GTP	0.014	0.067	-10000	0	-0.18	52	52
regulation of calcium-dependent cell-cell adhesion	-0.025	0.075	0.15	64	-0.15	1	65
ARF1/GTP	0.034	0.063	-10000	0	-0.14	53	53
mol:GM1	0.002	0.048	-10000	0	-0.13	51	51
mol:Choline	-0.016	0.042	0.086	3	-0.13	44	47
lamellipodium assembly	-0.009	0.1	-10000	0	-0.36	35	35
MAPK3	0.011	0.084	0.14	37	-0.29	27	64
ARF6/GTP/NME1/Tiam1	0.026	0.075	0.15	1	-0.15	64	65
ARF1	0.035	0.008	-10000	0	0	24	24
ARF6/GDP	0.014	0.095	-10000	0	-0.35	28	28
ARF1/GDP	0.012	0.1	-10000	0	-0.28	48	48
ARF6	0.039	0.042	-10000	0	-0.13	26	26
RAB11A	0.036	0.006	-10000	0	0	16	16
TIAM1	0.029	0.023	-10000	0	-0.044	34	34
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.011	0.083	-10000	0	-0.3	26	26
actin filament bundle formation	-0.017	0.11	0.28	52	-10000	0	52
KALRN	0.006	0.071	0.13	3	-0.26	29	32
RAB11FIP3/RAB11A	0.048	0.035	-10000	0	-0.16	12	12
RhoA/GDP	0.018	0.11	-10000	0	-0.28	52	52
NME1	-0.001	0.008	-10000	0	-0.03	26	26
Rac1/GDP	0.013	0.091	-10000	0	-0.29	32	32
substrate adhesion-dependent cell spreading	0.014	0.067	-10000	0	-0.18	52	52
cortical actin cytoskeleton organization	-0.009	0.1	-10000	0	-0.37	35	35
RAC1	0.025	0.017	-10000	0	0	163	163
liver development	0.014	0.067	-10000	0	-0.18	52	52
ARF6/GTP	0.014	0.067	-10000	0	-0.18	52	52
RhoA/GTP	0.033	0.065	-10000	0	-0.14	55	55
mol:GDP	-0.007	0.1	0.18	2	-0.3	50	52
ARF6/GTP/RAB11FIP3/RAB11A	0.05	0.07	-10000	0	-0.13	61	61
RHOA	0.035	0.007	-10000	0	0	21	21
PLD1	0.011	0.053	-10000	0	-0.14	48	48
RAB11FIP3	0.036	0.006	-10000	0	0	15	15
tube morphogenesis	-0.009	0.1	-10000	0	-0.36	35	35
ruffle organization	-0.004	0.066	-10000	0	-0.21	39	39
regulation of epithelial cell migration	0.014	0.067	-10000	0	-0.18	52	52
PLD2	0.012	0.053	-10000	0	-0.14	50	50
PIP5K1A	-0.004	0.067	-10000	0	-0.21	39	39
mol:Phosphatidic acid	-0.016	0.042	0.086	3	-0.13	44	47
Rac1/GTP	-0.009	0.1	-10000	0	-0.37	35	35

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.029	0.041	-10000	0	-0.14	17	17
VLDLR	0.027	0.016	-10000	0	0	137	137
CRKL	0.035	0.008	-10000	0	0	28	28
LRPAP1	0.036	0.007	-10000	0	0	17	17
FYN	0.03	0.014	-10000	0	0	88	88
ITGA3	0.033	0.011	-10000	0	0	56	56
RELN/VLDLR/Fyn	0.017	0.062	-10000	0	-0.13	53	53
MAPK8IP1/MKK7/MAP3K11/JNK1	0.067	0.062	-10000	0	-0.12	4	4
AKT1	-0.014	0.067	-10000	0	-0.19	49	49
MAP2K7	0.035	0.007	-10000	0	0	22	22
RAPGEF1	0.035	0.007	-10000	0	0	18	18
DAB1	0.036	0.005	-10000	0	0	8	8
RELN/LRP8/DAB1	0.042	0.036	-10000	0	-0.11	2	2
LRPAP1/LRP8	0.045	0.036	-10000	0	-0.15	14	14
RELN/LRP8/DAB1/Fyn	0.042	0.06	-10000	0	-0.12	33	33
DAB1/alpha3/beta1 Integrin	0.028	0.059	-10000	0	-0.12	20	20
long-term memory	0.042	0.064	-10000	0	-0.12	30	30
DAB1/LIS1	0.048	0.072	-10000	0	-0.13	30	30
DAB1/CRLK/C3G	0.038	0.059	-10000	0	-0.12	23	23
PIK3CA	0.031	0.014	-10000	0	0	82	82
DAB1/NCK2	0.049	0.072	-10000	0	-0.13	28	28
ARHGEF2	0.035	0.007	-10000	0	0	21	21
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.036	0.007	-10000	0	0	17	17
CDK5R1	0.035	0.008	-10000	0	0	25	25
RELN	0.023	0.018	-10000	0	0	186	186
PIK3R1	0.032	0.012	-10000	0	0	63	63
RELN/LRP8/Fyn	0.03	0.056	-10000	0	-0.13	34	34
GRIN2A/RELN/LRP8/DAB1/Fyn	0.052	0.071	-10000	0	-0.12	33	33
MAPK8	0.026	0.017	-10000	0	0	143	143
RELN/VLDLR/DAB1	0.03	0.045	-10000	0	-0.11	20	20
ITGB1	0.026	0.017	-10000	0	0	144	144
MAP1B	0.023	0.083	0.16	108	-0.21	4	112
RELN/LRP8	0.04	0.043	-10000	0	-0.13	10	10
GRIN2B/RELN/LRP8/DAB1/Fyn	0.052	0.07	-10000	0	-0.12	31	31
PI3K	0.018	0.076	-10000	0	-0.16	72	72
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.034	0.027	-10000	0	-0.14	1	1
RAP1A	0.031	0.11	0.25	37	-10000	0	37
PAFAH1B1	0.035	0.008	-10000	0	0	25	25
MAPK8IP1	0.035	0.008	-10000	0	0	24	24
CRLK/C3G	0.05	0.015	-10000	0	-10000	0	0
GRIN2B	0.035	0.008	-10000	0	0	23	23
NCK2	0.036	0.007	-10000	0	0	17	17
neuron differentiation	0.008	0.065	-10000	0	-0.22	16	16
neuron adhesion	0.031	0.11	0.25	41	-10000	0	41
LRP8	0.034	0.009	-10000	0	0	34	34
GSK3B	-0.008	0.077	-10000	0	-0.21	36	36
RELN/VLDLR/DAB1/Fyn	0.03	0.066	-10000	0	-0.12	53	53
MAP3K11	0.036	0.005	-10000	0	0	8	8
RELN/VLDLR/DAB1/P13K	-0.007	0.073	-10000	0	-0.19	54	54
CDK5	0.023	0.018	-10000	0	0	185	185
MAPT	-0.014	0.069	0.32	6	-10000	0	6
neuron migration	0	0.12	0.2	77	-0.28	32	109
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.008	0.065	-10000	0	-0.22	16	16
RELN/VLDLR	0.044	0.06	-10000	0	-0.12	25	25

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.044	0.043	-10000	0	-0.14	24	24
AKT1	-0.013	0.17	0.29	16	-0.42	44	60
PTK2B	-0.001	0.11	0.25	24	-0.4	11	35
VEGFR2 homodimer/Frs2	0.026	0.083	0.19	2	-0.33	15	17
CAV1	0.016	0.018	-10000	0	0	288	288
CALM1	0.033	0.012	-10000	0	0	57	57
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.022	0.086	0.18	1	-0.3	18	19
endothelial cell proliferation	0.018	0.15	0.31	30	-0.39	26	56
mol:Ca2+	0.007	0.13	0.24	54	-0.32	20	74
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.02	0.088	0.2	2	-0.27	22	24
RP11-342D11.1	-0.004	0.1	0.18	48	-0.34	18	66
CDH5	0.03	0.014	-10000	0	0	92	92
VEGFA homodimer	0.036	0.034	-10000	0	-0.1	13	13
SHC1	0.033	0.011	-10000	0	0	52	52
SHC2	0.032	0.012	-10000	0	0	61	61
HRAS/GDP	0.004	0.091	-10000	0	-0.24	46	46
SH2D2A	0.036	0.006	-10000	0	0	15	15
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.022	0.11	0.28	2	-0.37	17	19
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.023	0.087	0.18	1	-0.32	17	18
VEGFR1 homodimer	0.034	0.009	-10000	0	0	34	34
SHC/GRB2/SOS1	0.037	0.1	-10000	0	-0.23	46	46
GRB10	-0.012	0.11	0.21	33	-0.33	32	65
PTPN11	0.036	0.005	-10000	0	0	11	11
GRB2	0.035	0.007	-10000	0	0	18	18
PAK1	0.036	0.006	-10000	0	0	16	16
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.038	0.12	0.24	1	-0.28	37	38
HRAS	0.034	0.009	-10000	0	0	36	36
VEGF/Rho/ROCK1/Integrin Complex	0.012	0.11	0.18	5	-0.32	30	35
HIF1A	0.034	0.01	-10000	0	0	44	44
FRS2	0.035	0.009	-10000	0	0	30	30
oxygen and reactive oxygen species metabolic process	0.018	0.085	0.2	2	-0.27	22	24
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.036	0.005	-10000	0	0	10	10
Nck/Pak	0.048	0.025	-10000	0	-0.14	6	6
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.01	0.1	-10000	0	-0.3	29	29
mol:GDP	0.018	0.094	-10000	0	-0.23	46	46
mol:NADP	0.035	0.12	0.32	22	-0.33	17	39
eNOS/Hsp90	0.032	0.12	0.3	22	-0.32	17	39
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	0.007	0.13	0.25	54	-0.32	20	74
HIF1A/ARNT	0.046	0.032	-10000	0	-0.14	11	11
SHB	0.033	0.011	-10000	0	0	51	51
VEGFA	-0.003	0.013	-10000	0	-0.041	52	52
VEGFC	0.033	0.011	-10000	0	0	50	50
FAK1/Vinculin	0.013	0.12	0.27	12	-0.45	19	31
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.035	0.007	-10000	0	0	21	21
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.037	0.1	0.21	1	-0.29	25	26
PTPN6	0.033	0.011	-10000	0	0	53	53
EPAS1	0.033	0.062	-10000	0	-0.31	11	11
mol:L-citrulline	0.035	0.12	0.32	22	-0.33	17	39
ITGAV	0.035	0.009	-10000	0	0	31	31
PIK3CA	0.031	0.014	-10000	0	0	82	82
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.039	0.095	0.21	1	-0.29	20	21
VEGFR2 homodimer/VEGFA homodimer	0.012	0.099	-10000	0	-0.26	46	46
VEGFR2/3 heterodimer	0.026	0.085	0.19	2	-0.33	16	18
VEGFB	0.036	0.004	-10000	0	0	7	7
MAPK11	0.009	0.13	0.28	36	-0.35	20	56
VEGFR2 homodimer	-0.005	0.082	0.2	1	-0.4	14	15
FLT1	0.034	0.009	-10000	0	0	34	34
NEDD4	0.029	0.034	0.093	7	-0.057	54	61
MAPK3	0.018	0.13	0.29	43	-0.3	20	63
MAPK1	0.015	0.13	0.29	45	-0.3	20	65
VEGFA145/NRP2	0.023	0.022	-10000	0	-0.038	38	38
VEGFR1/2 heterodimer	0.024	0.084	0.19	1	-0.33	16	17
KDR	-0.005	0.082	0.2	1	-0.4	14	15
VEGFA165/NRP1/VEGFR2 homodimer	0.024	0.1	0.2	11	-0.23	46	57
SRC	0.034	0.009	-10000	0	0	34	34
platelet activating factor biosynthetic process	0.018	0.13	0.29	43	-0.31	20	63
PI3K	0.004	0.14	0.28	17	-0.38	32	49
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.021	0.087	0.18	1	-0.31	18	19
FES	0.008	0.13	0.24	69	-0.34	18	87
GAB1	0.013	0.12	0.26	10	-0.38	24	34
VEGFR2 homodimer/VEGFA homodimer/Src	0.02	0.085	-10000	0	-0.3	18	18
CTNNB1	0.036	0.006	-10000	0	0	15	15
SOS1	0	0	-10000	0	-10000	0	0
ARNT	0.036	0.004	-10000	0	0	6	6
eNOS/Caveolin-1	0.01	0.096	0.3	5	-0.39	11	16
VEGFR2 homodimer/VEGFA homodimer/Yes	0.019	0.09	-10000	0	-0.31	20	20
PI3K/GAB1	0.002	0.16	0.28	20	-0.4	45	65
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.06	0.098	0.24	2	-0.28	17	19
PRKACA	0.035	0.008	-10000	0	0	24	24
VEGFR2/3 heterodimer/VEGFC homodimer	0.039	0.081	-10000	0	-0.31	14	14
HSP90AA1	0	0	-10000	0	-10000	0	0
CDC42	0.007	0.13	0.23	67	-0.34	18	85
actin cytoskeleton reorganization	0.023	0.086	0.18	1	-0.32	17	18
PTK2	0.013	0.13	0.26	20	-0.48	18	38
EDG1	0	0.14	0.23	65	-0.36	28	93
mol:DAG	0.007	0.13	0.25	54	-0.32	20	74
CaM/Ca2+	0.019	0.12	0.26	23	-0.31	25	48
MAP2K3	0	0.12	0.27	35	-0.34	17	52
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.045	0.14	0.23	102	-0.3	43	145
PLCG1	0.006	0.13	0.25	54	-0.33	20	74
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.035	0.089	0.21	1	-0.29	18	19
IQGAP1	0.033	0.011	-10000	0	0	47	47
YES1	0.034	0.01	-10000	0	0	39	39
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.022	0.09	0.18	1	-0.31	20	21
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.019	0.087	0.18	1	-0.3	19	20
cell migration	0.006	0.13	0.26	23	-0.4	29	52
mol:PI-3-4-5-P3	0.005	0.14	0.27	18	-0.36	32	50
FYN	0.03	0.014	-10000	0	0	88	88
VEGFB/NRP1	0.006	0.12	0.22	56	-0.33	18	74
mol:NO	0.035	0.12	0.32	22	-0.33	17	39
PXN	0.036	0.004	-10000	0	0	7	7
HRAS/GTP	-0.045	0.07	-10000	0	-0.24	43	43
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.006	0.098	-10000	0	-0.3	43	43
VHL	0	0	-10000	0	-10000	0	0
ITGB3	0.036	0.003	-10000	0	0	4	4
NOS3	0.034	0.13	0.33	20	-0.37	17	37
VEGFR2 homodimer/VEGFA homodimer/Sck	0.016	0.094	-10000	0	-0.3	26	26
RAC1	0.025	0.017	-10000	0	0	163	163
PRKCA	0.001	0.12	0.27	34	-0.31	20	54
PRKCB	0.004	0.12	0.26	35	-0.31	20	55
VCL	0.026	0.017	-10000	0	0	154	154
VEGFA165/NRP1	-0.025	0.083	0.13	38	-0.23	46	84
VEGFR1/2 heterodimer/VEGFA homodimer	0.021	0.087	0.18	1	-0.31	18	19
VEGFA165/NRP2	0.023	0.022	-10000	0	-0.038	38	38
MAPKKK cascade	-0.03	0.093	0.17	11	-0.32	32	43
NRP2	0.036	0.005	-10000	0	0	8	8
VEGFC homodimer	0.033	0.011	-10000	0	0	50	50
NCK1	0.035	0.008	-10000	0	0	27	27
ROCK1	0.036	0.006	-10000	0	0	15	15
FAK1/Paxillin	0.03	0.13	0.27	16	-0.46	18	34
MAP3K13	0.007	0.13	0.28	38	-0.35	17	55
PDPK1	-0.013	0.13	0.25	30	-0.33	31	61

×

ErbB2/ErbB3 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.015	0.013	0.085	5	-10000	0	5
RAS family/GTP	0.012	0.11	0.22	1	-0.18	77	78
NFATC4	-0.022	0.067	0.17	17	-0.2	5	22
ERBB2IP	0.035	0.01	-10000	0	-0.001	37	37
HSP90 (dimer)	0	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.03	0.078	0.18	7	-0.18	20	27
JUN	-0.005	0.086	0.22	5	-0.36	7	12
HRAS	0.034	0.009	-10000	0	0	36	36
DOCK7	-0.037	0.068	0.16	9	-0.16	71	80
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.026	0.081	0.21	14	-0.13	86	100
AKT1	-0.01	0.008	0.014	29	-10000	0	29
BAD	-0.015	0.014	0.085	7	-10000	0	7
MAPK10	0.004	0.07	0.16	35	-0.15	12	47
mol:GTP	0	0.002	0.003	1	-0.005	26	27
ErbB2/ErbB3/neuregulin 1 beta	-0.031	0.083	0.2	7	-0.2	18	25
RAF1	-0.021	0.1	0.25	10	-0.24	34	44
ErbB2/ErbB3/neuregulin 2	0.001	0.073	0.21	15	-0.13	91	106
STAT3	-0.024	0.24	-10000	0	-0.9	35	35
cell migration	-0.01	0.067	0.18	16	-0.17	17	33
mol:PI-3-4-5-P3	-0.001	0.002	0.004	16	-0.004	20	36
cell proliferation	-0.042	0.24	0.44	3	-0.58	60	63
FOS	-0.032	0.2	0.38	6	-0.42	93	99
NRAS	0.032	0.012	-10000	0	0	63	63
mol:Ca2+	-0.03	0.078	0.18	7	-0.18	20	27
MAPK3	-0.02	0.18	0.4	3	-0.48	40	43
MAPK1	-0.044	0.22	0.4	3	-0.57	52	55
JAK2	-0.028	0.076	0.17	17	-0.18	19	36
NF2	0.01	0.008	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.005	0.08	0.15	12	-0.17	89	101
NRG1	0.036	0.005	-10000	0	0	9	9
GRB2/SOS1	0.024	0.021	-10000	0	-0.14	8	8
MAPK8	-0.018	0.088	0.18	3	-0.23	48	51
MAPK9	0.01	0.073	0.16	46	-0.14	4	50
ERBB2	-0.016	0.069	0.26	30	-10000	0	30
ERBB3	0.018	0.018	-10000	0	0	257	257
SHC1	0.033	0.011	-10000	0	0	52	52
RAC1	0.025	0.017	-10000	0	0	163	163
apoptosis	0.012	0.03	0.2	10	-0.069	4	14
STAT3 (dimer)	-0.022	0.24	-10000	0	-0.88	35	35
RNF41	-0.021	0.02	0.076	10	-0.12	6	16
FRAP1	-0.016	0.012	0.084	5	-10000	0	5
RAC1-CDC42/GTP	-0.023	0.044	-10000	0	-0.13	47	47
ErbB2/ErbB2/HSP90 (dimer)	-0.025	0.008	-10000	0	-10000	0	0
CHRNA1	-0.007	0.15	0.36	5	-0.36	44	49
myelination	-0.036	0.071	0.22	9	-0.21	5	14
PPP3CB	-0.022	0.067	0.17	16	-0.18	16	32
KRAS	0.034	0.009	-10000	0	0	34	34
RAC1-CDC42/GDP	0.021	0.075	0.22	1	-0.16	48	49
NRG2	0.036	0.004	-10000	0	0	7	7
mol:GDP	-0.005	0.08	0.15	12	-0.17	89	101
SOS1	0	0.001	-10000	0	-0.004	9	9
MAP2K2	-0.029	0.1	0.22	11	-0.25	41	52
SRC	0.034	0.009	-10000	0	0	34	34
mol:cAMP	-0.001	0.001	0.003	4	-0.004	1	5
PTPN11	-0.033	0.082	0.17	20	-0.18	20	40
MAP2K1	-0.038	0.2	0.39	2	-0.56	37	39
heart morphogenesis	-0.03	0.078	0.18	7	-0.18	20	27
RAS family/GDP	0.02	0.11	0.24	1	-0.18	79	80
GRB2	0.035	0.007	-10000	0	0	18	18
PRKACA	0.018	0.009	-10000	0	-10000	0	0
CHRNE	0.001	0.025	0.076	2	-0.13	7	9
HSP90AA1	0	0	-10000	0	-10000	0	0
activation of caspase activity	0.01	0.008	-10000	0	-0.014	29	29
nervous system development	-0.03	0.078	0.18	7	-0.18	20	27
CDC42	0.035	0.008	-10000	0	0	26	26

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.033	0.011	-10000	0	0	46	46
VLDLR	0.027	0.016	-10000	0	0	137	137
LRPAP1	0.036	0.007	-10000	0	0	17	17
NUDC	0.035	0.008	-10000	0	0	28	28
RELN/LRP8	0.04	0.043	-10000	0	-0.13	10	10
CaM/Ca2+	0.02	0.027	-10000	0	-0.13	14	14
KATNA1	0.034	0.01	-10000	0	0	45	45
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	0.036	0.1	0.19	138	-0.2	5	143
IQGAP1/CaM	0.031	0.059	-10000	0	-0.15	45	45
DAB1	0.036	0.005	-10000	0	0	8	8
IQGAP1	0.033	0.011	-10000	0	0	47	47
PLA2G7	0.033	0.011	-10000	0	0	51	51
CALM1	0.033	0.012	-10000	0	0	57	57
DYNLT1	0.034	0.01	-10000	0	0	44	44
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.045	0.036	-10000	0	-0.15	14	14
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0	0	-10000	0	-10000	0	0
CDK5R1	0.035	0.008	-10000	0	0	25	25
LIS1/Poliovirus Protein 3A	-0.023	0.029	-10000	0	-0.14	24	24
CDK5R2	0.036	0.006	-10000	0	0	16	16
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	0.031	0.048	-10000	0	-0.13	20	20
YWHAE	0.035	0.008	-10000	0	0	27	27
NDEL1/14-3-3 E	0.06	0.17	0.32	135	-0.26	17	152
MAP1B	-0.014	0.067	-10000	0	-0.2	51	51
RAC1	-0.003	0.051	-10000	0	-0.27	11	11
p35/CDK5	-0.026	0.055	0.2	7	-0.21	11	18
RELN	0.023	0.018	-10000	0	0	186	186
PAFAH/LIS1	0.021	0.04	-10000	0	-0.15	22	22
LIS1/CLIP170	-0.023	0.029	-10000	0	-0.14	24	24
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.037	0.074	0.14	9	-0.27	26	35
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.013	0.088	0.17	1	-0.23	53	54
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	0.053	0.16	0.3	131	-0.26	14	145
LIS1/IQGAP1	0.013	0.059	-10000	0	-0.15	50	50
RHOA	-0.006	0.066	-10000	0	-0.27	19	19
PAFAH1B1	-0.02	0.008	-10000	0	-10000	0	0
PAFAH1B3	0.031	0.013	-10000	0	0	78	78
PAFAH1B2	0.036	0.005	-10000	0	0	8	8
MAP1B/LIS1/Dynein heavy chain	0.005	0.079	-10000	0	-0.2	55	55
NDEL1/Katanin 60/Dynein heavy chain	0.079	0.15	0.33	111	-0.25	23	134
LRP8	0.034	0.009	-10000	0	0	34	34
NDEL1/Katanin 60	0.053	0.16	0.31	127	-0.25	18	145
P39/CDK5	-0.025	0.055	0.2	7	-0.21	11	18
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.02	0.053	-10000	0	-0.19	26	26
CDK5	-0.013	0.043	0.19	8	-0.2	5	13
PPP2R5D	0.036	0.004	-10000	0	0	5	5
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.018	0.024	-10000	0	-0.12	24	24
CSNK2A1	0.033	0.011	-10000	0	0	51	51
RELN/VLDLR/DAB1/LIS1	0.033	0.061	-10000	0	-0.14	32	32
RELN/VLDLR	0.044	0.06	-10000	0	-0.12	25	25
CDC42	-0.003	0.048	-10000	0	-0.2	17	17

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.035	0.008	-10000	0	0	28	28
Rac1/GDP	0.025	0.02	-10000	0	-0.025	11	11
DOCK1	0.024	0.018	-10000	0	0	183	183
ITGA4	0.036	0.006	-10000	0	0	13	13
RAC1	0.025	0.017	-10000	0	0	163	163
alpha4/beta7 Integrin	0.052	0.012	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.035	0.008	-10000	0	0	23	23
alpha4/beta1 Integrin	0.051	0.035	-10000	0	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.052	0.018	-10000	0	-10000	0	0
lamellipodium assembly	-0.047	0.14	-10000	0	-0.35	80	80
PIK3CA	0.031	0.014	-10000	0	0	82	82
PI3K	0.018	0.076	-10000	0	-0.16	72	72
ARF6	0.035	0.009	-10000	0	0	29	29
TLN1	0.029	0.015	-10000	0	0	101	101
PXN	-0.021	0.01	0.093	3	-10000	0	3
PIK3R1	0.032	0.012	-10000	0	0	63	63
ARF6/GTP	0.048	0.049	-10000	0	-0.12	1	1
cell adhesion	0.044	0.052	-10000	0	-0.12	12	12
CRKL/CBL	0.051	0.014	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.039	0.027	-10000	0	-10000	0	0
ITGB1	0.026	0.017	-10000	0	0	144	144
ITGB7	0.036	0.006	-10000	0	0	14	14
ARF6/GDP	0.035	0.015	-10000	0	-0.025	13	13
alpha4/beta1 Integrin/Paxillin/VCAM1	0.011	0.081	-10000	0	-0.12	117	117
p130Cas/Crk/Dock1	0.027	0.036	-10000	0	-0.11	18	18
VCAM1	0.023	0.018	-10000	0	0	195	195
alpha4/beta1 Integrin/Paxillin/Talin	0.046	0.053	-10000	0	-0.12	12	12
alpha4/beta1 Integrin/Paxillin/GIT1	0.052	0.048	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.05	0.047	-10000	0	-10000	0	0
CBL	0.036	0.005	-10000	0	0	8	8
PRKACA	0.035	0.008	-10000	0	0	24	24
GIT1	0.037	0.003	-10000	0	0	3	3
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.046	0.053	-10000	0	-0.12	12	12
Rac1/GTP	-0.053	0.16	-10000	0	-0.39	80	80

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.035	0.009	-10000	0	0	31	31
SPHK1	0.033	0.011	-10000	0	0	51	51
GNAI2	0.034	0.01	-10000	0	0	44	44
mol:S1P	0.018	0.016	-10000	0	-10000	0	0
GNAO1	0.03	0.014	-10000	0	0	87	87
mol:Sphinganine-1-P	-0.011	0.032	0.093	43	-10000	0	43
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.028	0.046	-10000	0	-0.18	3	3
GNAI3	0.036	0.006	-10000	0	0	14	14
G12/G13	0.025	0.048	-10000	0	-0.14	28	28
S1PR3	0	0	-10000	0	-10000	0	0
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	0.034	0.01	-10000	0	0	45	45
S1P1/S1P	0.035	0.033	-10000	0	-10000	0	0
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
GNAI1	0.018	0.018	-10000	0	0	262	262
S1P/S1P5/G12	0.017	0.037	-10000	0	-0.18	3	3
S1P/S1P3/Gq	0.027	0.04	0.15	6	-0.26	6	12
S1P/S1P4/Gi	-0.004	0.11	-10000	0	-0.29	43	43
GNAQ	0.035	0.009	-10000	0	0	30	30
GNAZ	0.031	0.013	-10000	0	0	80	80
GNA14	0.035	0.009	-10000	0	0	29	29
GNA15	0.033	0.011	-10000	0	0	51	51
GNA12	0.023	0.018	-10000	0	0	189	189
GNA13	0.035	0.007	-10000	0	0	20	20
GNA11	0.033	0.011	-10000	0	0	51	51
ABCC1	0.035	0.007	-10000	0	0	19	19

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	0.063	0.065	-9999	-0.12	12	12
SMAD6-7/SMURF1	0.045	0.038	-9999	-0.13	3	3
NOG	0	0	-9999	-10000	0	0
SMAD9	-0.025	0.15	-9999	-0.44	54	54
SMAD4	0.032	0.012	-9999	0	59	59
SMAD5	-0.027	0.095	-9999	-0.3	42	42
BMP7/USAG1	0.033	0.027	-9999	-10000	0	0
SMAD5/SKI	-0.021	0.11	-9999	-0.3	45	45
SMAD1	-0.033	0.15	-9999	-0.38	58	58
BMP2	0.028	0.016	-9999	0	125	125
SMAD1/SMAD1/SMAD4	-0.011	0.13	-9999	-0.35	46	46
BMPR1A	0.025	0.017	-9999	0	169	169
BMPR1B	0.036	0.006	-9999	0	12	12
BMPR1A-1B/BAMBI	0.021	0.06	-9999	-0.13	48	48
AHSG	0.035	0.009	-9999	0	29	29
CER1	0.032	0.013	-9999	0	71	71
BMP2-4/CER1	0.037	0.055	-9999	-0.12	34	34
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.009	0.077	-9999	-0.25	26	26
BMP2-4 (homodimer)	0.028	0.051	-9999	-0.14	34	34
RGMB	0	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.054	0.058	-9999	-0.12	12	12
RGMA	0	0	-9999	-10000	0	0
SMURF1	0.025	0.017	-9999	0	164	164
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.019	0.068	-9999	-0.16	58	58
BMP2-4/USAG1	0.033	0.045	-9999	-0.12	14	14
SMAD6/SMURF1/SMAD5	-0.012	0.09	-9999	-0.28	35	35
SOSTDC1	0.023	0.018	-9999	0	184	184
BMP7/BMPR2/BMPR1A-1B	0.054	0.058	-9999	-0.12	14	14
SKI	0.037	0	-9999	-10000	0	0
BMP6 (homodimer)	0.035	0.008	-9999	0	25	25
HFE2	0	0	-9999	-10000	0	0
ZFYVE16	0.034	0.009	-9999	0	35	35
MAP3K7	0.034	0.01	-9999	0	43	43
BMP2-4/CHRD	0.041	0.055	-9999	-0.12	33	33
SMAD5/SMAD5/SMAD4	-0.023	0.11	-9999	-0.31	45	45
MAPK1	0.034	0.01	-9999	0	44	44
TAK1/TAB family	0.019	0.084	-9999	-0.21	15	15
BMP7 (homodimer)	0.034	0.01	-9999	0	41	41
NUP214	0.035	0.007	-9999	0	18	18
BMP6/FETUA	0.049	0.016	-9999	-10000	0	0
SMAD1/SKI	-0.016	0.15	-9999	-0.36	60	60
SMAD6	0.036	0.005	-9999	0	9	9
CTDSP2	0.033	0.012	-9999	0	58	58
BMP2-4/FETUA	0.04	0.055	-9999	-0.12	34	34
MAP3K7IP1	0.034	0.009	-9999	0	36	36
GREM1	0.032	0.012	-9999	0	60	60
BMPR2 (homodimer)	0.036	0.005	-9999	0	10	10
GADD34/PP1CA	0.051	0.055	-9999	-0.13	33	33
BMPR1A-1B (homodimer)	0.034	0.032	-9999	-0.14	6	6
CHRDL1	0	0	-9999	-10000	0	0
ENDOFIN/SMAD1	-0.019	0.16	-9999	-0.38	60	60
SMAD6-7/SMURF1/SMAD1	0.003	0.14	-9999	-0.36	47	47
SMAD6/SMURF1	0.025	0.017	-9999	0	164	164
BAMBI	0.018	0.018	-9999	0	259	259
SMURF2	0.035	0.007	-9999	0	19	19
BMP2-4/CHRDL1	0.026	0.044	-9999	-0.12	34	34
BMP2-4/GREM1	0.037	0.055	-9999	-0.12	33	33
SMAD7	0.034	0.01	-9999	0	45	45
SMAD8A/SMAD8A/SMAD4	-0.014	0.15	-9999	-0.41	61	61
SMAD1/SMAD6	-0.017	0.14	-9999	-0.36	51	51
TAK1/SMAD6	0.033	0.034	-9999	-0.14	8	8
BMP7	0.034	0.01	-9999	0	41	41
BMP6	0.035	0.008	-9999	0	25	25
MAP3K7IP2	0.033	0.011	-9999	0	47	47
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.003	0.056	-9999	-0.22	16	16
PPM1A	0.035	0.009	-9999	0	31	31
SMAD1/SMURF2	-0.017	0.16	-9999	-0.38	58	58
SMAD7/SMURF1	0.033	0.03	-9999	-0.14	3	3
CTDSPL	0.036	0.006	-9999	0	13	13
PPP1CA	0.035	0.007	-9999	0	19	19
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0.036	0.006	-9999	0	15	15
PPP1R15A	0.033	0.011	-9999	0	53	53
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.013	0.069	-9999	-0.21	28	28
CHRD	0.035	0.008	-9999	0	23	23
BMPR2	0.036	0.005	-9999	0	10	10
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.019	0.07	-9999	-0.17	55	55
BMP4	0.033	0.011	-9999	0	51	51
FST	0.033	0.011	-9999	0	48	48
BMP2-4/NOG	0.026	0.044	-9999	-0.12	34	34
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.051	0.062	-9999	-0.12	9	9

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0.036	0.006	-10000	0	0	15	15
MKNK1	0.034	0.009	-10000	0	0	35	35
mol:PIP3	-0.019	0.058	0.093	5	-0.24	21	26
FRAP1	0.035	0.1	0.28	2	-0.5	11	13
AKT1	0.015	0.11	0.16	118	-0.26	30	148
INSR	0.035	0.008	-10000	0	0	23	23
Insulin Receptor/Insulin	0.046	0.013	-10000	0	-10000	0	0
mol:GTP	0.04	0.11	0.2	75	-0.25	33	108
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.004	0.046	-10000	0	-0.19	15	15
TSC2	0.035	0.008	-10000	0	0	28	28
RHEB/GDP	0.006	0.076	0.13	2	-0.21	36	38
TSC1	0.034	0.01	-10000	0	0	40	40
Insulin Receptor/IRS1	0.023	0.06	-10000	0	-0.25	22	22
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.029	0.071	-10000	0	-0.23	13	13
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.043	0.086	0.25	10	-0.32	4	14
MAP3K5	-0.027	0.085	0.16	1	-0.23	73	74
PIK3R1	0.033	0.012	-10000	0	0	63	63
apoptosis	-0.026	0.085	0.16	1	-0.23	73	74
mol:LY294002	0	0	0.001	9	-0.001	18	27
EIF4B	0.037	0.082	0.23	13	-0.3	5	18
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.034	0.073	0.23	7	-0.27	4	11
eIF4E/eIF4G1/eIF4A1	0.011	0.074	-10000	0	-0.33	12	12
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.023	0.083	-10000	0	-0.23	33	33
mTOR/RHEB/GTP/Raptor/GBL	0.013	0.065	0.19	18	-0.2	12	30
FKBP1A	0.032	0.012	-10000	0	0	63	63
RHEB/GTP	0.022	0.089	0.2	17	-0.21	34	51
mol:Amino Acids	0	0	0.001	9	-0.001	18	27
FKBP12/Rapamycin	0.021	0.024	-10000	0	-0.14	10	10
PDPK1	-0.02	0.063	0.16	17	-0.23	20	37
EIF4E	0.034	0.01	-10000	0	0	38	38
ASK1/PP5C	-0.031	0.24	-10000	0	-0.56	79	79
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.015	0.11	-10000	0	-0.34	32	32
TSC1/TSC2	0.044	0.12	0.21	75	-0.27	33	108
tumor necrosis factor receptor activity	0	0	0.001	18	-0.001	9	27
RPS6	0.031	0.014	-10000	0	0	86	86
PPP5C	0.034	0.01	-10000	0	0	39	39
EIF4G1	0.033	0.011	-10000	0	0	50	50
IRS1	0.001	0.059	-10000	0	-0.26	23	23
INS	0.036	0.006	-10000	0	0	16	16
PTEN	0.025	0.017	-10000	0	0	168	168
PDK2	-0.019	0.064	0.16	17	-0.23	21	38
EIF4EBP1	-0.024	0.26	-10000	0	-1.1	26	26
PIK3CA	0.031	0.014	-10000	0	0	82	82
PPP2R5D	0.029	0.094	0.27	3	-0.45	11	14
peptide biosynthetic process	-0.021	0.017	0.18	3	-10000	0	3
RHEB	0.025	0.017	-10000	0	0	167	167
EIF4A1	0.035	0.007	-10000	0	0	18	18
mol:Rapamycin	0	0.001	0.004	17	-0.003	14	31
EEF2	-0.021	0.017	0.18	3	-10000	0	3
eIF4E/4E-BP1	-0.008	0.25	-10000	0	-1.1	26	26

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.067	0.27	0.56	21	-0.68	26	47
CRP	0.058	0.26	0.57	13	-0.69	24	37
cell cycle arrest	0.05	0.29	0.53	19	-0.75	32	51
TIMP1	0.004	0.37	0.56	16	-0.79	72	88
IL6ST	0.028	0.033	0.09	2	-0.045	52	54
Rac1/GDP	0.041	0.11	0.3	16	-0.31	11	27
AP1	0.012	0.2	-10000	0	-0.56	38	38
GAB2	0.034	0.012	-10000	0	-0.041	1	1
TNFSF11	0.056	0.26	0.57	9	-0.74	20	29
HSP90B1	0.001	0.22	0.3	3	-0.84	30	33
GAB1	0.033	0.012	-10000	0	-0.042	1	1
MAPK14	0.028	0.067	0.21	2	-0.31	3	5
AKT1	-0.012	0.17	-10000	0	-0.6	27	27
FOXO1	-0.013	0.16	-10000	0	-0.53	31	31
MAP2K6	0.028	0.072	0.19	2	-0.26	8	10
mol:GTP	0	0.004	-10000	0	-0.022	1	1
MAP2K4	0.035	0.14	0.35	23	-0.35	17	40
MITF	0.031	0.085	0.23	12	-0.29	9	21
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.034	0.01	-10000	0	0	45	45
A2M	-0.076	0.34	-10000	0	-1.2	44	44
CEBPB	0.031	0.014	-10000	0	0	82	82
GRB2/SOS1/GAB family/SHP2	0.021	0.13	0.32	1	-0.48	24	25
STAT3	0.04	0.3	0.54	18	-0.8	32	50
STAT1	0.022	0.065	-10000	0	-0.71	3	3
CEBPD	0.023	0.34	0.55	11	-0.86	47	58
PIK3CA	0.031	0.014	-10000	0	0	83	83
PI3K	0.019	0.076	-10000	0	-0.16	73	73
JUN	0.034	0.01	-10000	0	0	41	41
PIAS3/MITF	0.078	0.11	0.27	24	-0.27	13	37
MAPK11	0.025	0.065	0.21	1	-0.31	3	4
STAT3 (dimer)/FOXO1	-0.021	0.26	0.46	8	-0.62	54	62
GRB2/SOS1/GAB family	0.043	0.13	0.24	2	-0.31	31	33
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	0.004	0.1	0.19	10	-0.28	39	49
GRB2	0.036	0.008	-10000	0	-0.002	19	19
JAK2	0.031	0.014	-10000	0	0	83	83
LBP	0.067	0.26	0.54	18	-0.62	28	46
PIK3R1	0.033	0.013	-10000	0	-0.042	1	1
JAK1	0.03	0.026	-10000	0	-0.043	47	47
MYC	0.011	0.37	0.56	16	-0.86	62	78
FGG	0.056	0.26	0.57	9	-0.74	20	29
macrophage differentiation	0.05	0.29	0.53	19	-0.75	32	51
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.054	0.074	-10000	0	-0.19	6	6
JUNB	0.051	0.3	0.51	28	-0.79	33	61
FOS	0.025	0.017	-10000	0	0	162	162
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.029	0.085	0.23	14	-0.29	10	24
STAT1/PIAS1	0.072	0.13	0.31	13	-0.35	7	20
GRB2/SOS1/GAB family/SHP2/PI3K	0	0.17	-10000	0	-0.52	32	32
STAT3 (dimer)	0.042	0.3	0.54	18	-0.79	32	50
PRKCD	0.11	0.22	0.4	107	-0.43	23	130
IL6R	0.03	0.027	-10000	0	-0.041	57	57
SOCS3	0.06	0.087	0.42	3	-10000	0	3
gp130 (dimer)/JAK1/JAK1/LMO4	0.044	0.089	0.18	1	-0.17	46	47
Rac1/GTP	0.038	0.12	0.3	14	-0.32	13	27
HCK	0.027	0.017	-10000	0	0	141	141
MAPKKK cascade	0.013	0.19	0.34	2	-0.6	34	36
bone resorption	0.058	0.25	0.56	9	-0.69	21	30
IRF1	0.05	0.3	0.54	20	-0.85	27	47
mol:GDP	0.031	0.09	0.24	16	-0.28	10	26
SOS1	0.001	0.004	0.026	10	-0.022	1	11
VAV1	0.03	0.09	0.24	17	-0.28	10	27
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.02	0.078	-10000	0	-0.33	13	13
PTPN11	0.015	0.099	-10000	0	-0.73	8	8
IL6/IL6RA	0.023	0.038	-10000	0	-10000	0	0
gp130 (dimer)/TYK2/TYK2/LMO4	0.047	0.075	-10000	0	-0.15	44	44
gp130 (dimer)/JAK2/JAK2/LMO4	0.047	0.065	-10000	0	-0.12	35	35
IL6	0.015	0.027	-10000	0	-0.041	25	25
PIAS3	0.036	0.006	-10000	0	0	15	15
PTPRE	0.009	0.03	-10000	0	-0.056	36	36
PIAS1	0.035	0.008	-10000	0	0	25	25
RAC1	0.025	0.018	-10000	0	0	163	163
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.025	0.057	0.17	4	-0.22	6	10
LMO4	0.029	0.033	0.09	2	-0.046	50	52
STAT3 (dimer)/PIAS3	0.012	0.27	0.48	5	-0.72	34	39
MCL1	-0.014	0.16	-10000	0	-0.7	17	17

×

Class I PI3K signaling events

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
ARF5/GTP	-0.022	0.054	0.16	16	-0.22	9	25
DAPP1	-0.022	0.13	0.18	1	-0.3	63	64
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.044	0.19	0.26	2	-0.49	57	59
mol:DAG	-0.007	0.091	0.19	21	-0.2	48	69
HRAS	0.035	0.02	0.077	2	-0.032	25	27
RAP1A	0.038	0.014	0.063	4	-0.019	20	24
ARF5/GDP	0.001	0.095	-10000	0	-0.32	30	30
PLCG2	0.032	0.012	-10000	0	0	63	63
PLCG1	0.034	0.01	-10000	0	0	37	37
ARF5	0.024	0.017	-10000	0	0	171	171
mol:GTP	-0.024	0.052	0.15	17	-0.2	10	27
ARF1/GTP	-0.018	0.047	0.12	16	-0.2	12	28
RHOA	0.035	0.007	-10000	0	0	21	21
YES1	0.034	0.01	-10000	0	0	39	39
RAP1A/GTP	-0.023	0.053	0.16	17	-0.2	10	27
ADAP1	-0.024	0.046	0.13	14	-0.19	10	24
ARAP3	-0.024	0.051	0.15	17	-0.2	10	27
INPPL1	0.036	0.006	-10000	0	0	13	13
PREX1	0	0	-10000	0	-10000	0	0
ARHGEF6	0.033	0.011	-10000	0	0	48	48
ARHGEF7	0.033	0.012	-10000	0	0	57	57
ARF1	0.035	0.008	-10000	0	0	24	24
NRAS	0.035	0.018	0.068	1	-0.033	12	13
FYN	0.03	0.014	-10000	0	0	88	88
ARF6	0.035	0.009	-10000	0	0	29	29
FGR	0.033	0.011	-10000	0	0	56	56
mol:Ca2+	0.007	0.061	0.15	35	-0.12	17	52
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.033	0.011	-10000	0	0	46	46
ZAP70	0.037	0.002	-10000	0	0	2	2
mol:IP3	-0.008	0.065	0.17	23	-0.17	18	41
LYN	0.031	0.013	-10000	0	0	74	74
ARF1/GDP	0.01	0.11	-10000	0	-0.34	34	34
RhoA/GDP	0.028	0.09	0.18	14	-0.22	30	44
PDK1/Src/Hsp90	0.046	0.014	-10000	0	-10000	0	0
BLNK	0.019	0.018	-10000	0	0	248	248
actin cytoskeleton reorganization	0.011	0.11	0.19	27	-0.29	26	53
SRC	0.034	0.009	-10000	0	0	34	34
PLEKHA2	-0.012	0.024	0.086	29	-10000	0	29
RAC1	0.025	0.017	-10000	0	0	163	163
PTEN	0.025	0.022	-10000	0	-0.033	17	17
HSP90AA1	0	0	-10000	0	-10000	0	0
ARF6/GTP	-0.025	0.055	0.16	17	-0.2	10	27
RhoA/GTP	-0.026	0.058	0.17	18	-0.21	11	29
Src family/SYK family/BLNK-LAT	-0.05	0.16	-10000	0	-0.35	84	84
BLK	0.036	0.007	-10000	0	0	17	17
PDPK1	0.036	0.005	-10000	0	0	8	8
CYTH1	-0.024	0.046	0.13	14	-0.19	10	24
HCK	0.027	0.016	-10000	0	0	141	141
CYTH3	-0.024	0.046	0.13	14	-0.19	10	24
CYTH2	-0.024	0.046	0.13	14	-0.19	10	24
KRAS	0.034	0.021	0.077	2	-0.032	30	32
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.003	0.031	0.21	2	-0.15	3	5
SGK1	0	0.03	0.21	1	-0.16	3	4
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.005	0.11	0.21	1	-0.34	35	36
SOS1	0	0	-10000	0	-10000	0	0
SYK	0.031	0.013	-10000	0	0	74	74
ARF6/GDP	-0.025	0.067	0.17	15	-0.22	27	42
mol:PI-3-4-5-P3	-0.025	0.049	0.14	14	-0.2	10	24
ARAP3/RAP1A/GTP	-0.023	0.053	0.16	17	-0.2	10	27
VAV1	0.034	0.009	-10000	0	0	33	33
mol:PI-3-4-P2	-0.011	0.002	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.068	0.097	0.21	123	-0.14	41	164
PLEKHA1	-0.007	0.022	0.086	23	-10000	0	23
Rac1/GDP	0.002	0.098	-10000	0	-0.31	31	31
LAT	0.036	0.005	-10000	0	0	9	9
Rac1/GTP	-0.004	0.15	0.16	1	-0.46	36	37
ITK	-0.027	0.049	0.13	15	-0.2	10	25
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.021	0.11	0.23	10	-0.28	53	63
LCK	0.035	0.007	-10000	0	0	18	18
BTK	-0.026	0.052	0.14	18	-0.2	10	28

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.041	0.089	0.24	21	-0.21	7	28
TBX21	0.069	0.2	0.58	6	-0.59	3	9
B2M	0.035	0.008	-10000	0	0	24	24
TYK2	0.036	0.039	0.12	16	-0.05	29	45
IL12RB1	0.037	0.04	0.12	15	-0.051	31	46
GADD45B	0.06	0.29	0.52	18	-0.99	24	42
IL12RB2	0.04	0.041	0.12	20	-0.052	23	43
GADD45G	0.093	0.19	0.54	9	-0.55	3	12
natural killer cell activation	0.012	0.024	0.056	75	-0.036	9	84
RELB	0.034	0.009	-10000	0	0	32	32
RELA	0.036	0.004	-10000	0	0	7	7
IL18	0.034	0.022	0.089	2	-0.043	17	19
IL2RA	0.024	0.018	-10000	0	0	177	177
IFNG	0.035	0.009	-10000	0	0	30	30
STAT3 (dimer)	0.073	0.22	0.47	20	-0.57	19	39
HLA-DRB5	-0.001	0.009	-10000	0	-0.023	45	45
FASLG	0.073	0.2	0.58	6	-0.6	2	8
NF kappa B2 p52/RelB	0.051	0.18	0.45	8	-0.51	10	18
CD4	0.024	0.027	-10000	0	-0.017	130	130
SOCS1	0.036	0.005	-10000	0	0	9	9
EntrezGene:6955	-0.001	0.01	-10000	0	-0.025	57	57
CD3D	0.025	0.028	-10000	0	-0.025	110	110
CD3E	0.028	0.027	-10000	0	-0.035	78	78
CD3G	0.027	0.029	-10000	0	-0.034	86	86
IL12Rbeta2/JAK2	0.055	0.059	0.18	18	-10000	0	18
CCL3	0.072	0.2	0.5	16	-0.51	11	27
CCL4	0.041	0.33	0.6	12	-1	31	43
HLA-A	0.036	0.006	-10000	0	0	12	12
IL18/IL18R	0.095	0.063	0.22	26	-0.11	16	42
NOS2	0.074	0.19	0.44	31	-0.44	14	45
IL12/IL12R/TYK2/JAK2/SPHK2	0.039	0.088	0.24	18	-0.21	7	25
IL1R1	0.071	0.2	0.59	8	-0.57	4	12
IL4	0.004	0.048	-10000	0	-0.077	74	74
JAK2	0.033	0.038	0.12	11	-0.051	22	33
EntrezGene:6957	-0.001	0.009	-10000	0	-0.023	45	45
TCR/CD3/MHC I/CD8	0.006	0.046	0.11	1	-0.18	16	17
RAB7A	0.092	0.2	0.45	29	-0.53	20	49
lysosomal transport	0.093	0.2	0.44	29	-0.51	20	49
FOS	-0.11	0.49	0.44	29	-1	101	130
STAT4 (dimer)	0.086	0.2	0.46	27	-0.5	15	42
STAT5A (dimer)	0.078	0.19	0.44	8	-0.51	11	19
GZMA	0.069	0.2	0.57	10	-0.59	3	13
GZMB	0.068	0.2	0.58	11	-0.54	7	18
HLX	0	0	-10000	0	-10000	0	0
LCK	0.062	0.2	0.52	15	-0.53	11	26
TCR/CD3/MHC II/CD4	-0.022	0.12	0.17	22	-0.2	126	148
IL2/IL2R	0.059	0.05	-10000	0	-10000	0	0
MAPK14	0.094	0.23	0.51	19	-0.64	19	38
CCR5	0.077	0.18	0.4	34	-0.4	16	50
IL1B	0.029	0.037	0.12	7	-0.051	26	33
STAT6	0.053	0.099	0.28	22	-0.4	3	25
STAT4	0.035	0.009	-10000	0	0	29	29
STAT3	0.034	0.01	-10000	0	0	37	37
STAT1	0.034	0.01	-10000	0	0	40	40
NFKB1	0.035	0.007	-10000	0	0	18	18
NFKB2	0.025	0.017	-10000	0	0	157	157
IL12B	0.04	0.041	0.12	20	-0.051	26	46
CD8A	0	0	-10000	0	-10000	0	0
CD8B	0	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.041	0.088	0.21	7	-0.24	22	29
IL2RB	0.033	0.011	-10000	0	0	53	53
proteasomal ubiquitin-dependent protein catabolic process	0.087	0.2	0.46	28	-0.47	15	43
IL2RG	0.035	0.008	-10000	0	0	24	24
IL12	0.062	0.06	0.2	13	-10000	0	13
STAT5A	0.036	0.004	-10000	0	0	5	5
CD247	-0.001	0.009	-10000	0	-0.023	45	45
IL2	0.036	0.005	-10000	0	0	9	9
SPHK2	0.035	0.009	-10000	0	0	31	31
FRAP1	0.036	0.006	-10000	0	0	16	16
IL12A	0.038	0.04	0.12	19	-0.051	32	51
IL12/IL12R/TYK2/JAK2	0.065	0.21	0.54	18	-0.56	11	29
MAP2K3	0.088	0.23	0.54	12	-0.65	19	31
RIPK2	0.036	0.006	-10000	0	0	14	14
MAP2K6	0.092	0.22	0.5	19	-0.59	19	38
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.021	0.027	-10000	0	-0.012	183	183
IL18RAP	0.039	0.02	0.084	3	-0.041	22	25
IL12Rbeta1/TYK2	0.049	0.063	0.18	7	-0.16	14	21
EOMES	-0.019	0.038	0.076	2	-0.1	47	49
STAT1 (dimer)	0.086	0.19	0.45	21	-0.47	8	29
T cell proliferation	0.075	0.18	0.4	34	-0.41	19	53
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.039	0.02	0.084	3	-0.041	22	25
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.046	0.17	-10000	0	-0.47	23	23
ATF2	0.086	0.22	0.47	19	-0.6	19	38

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.001	0.04	-10000	0	-10000	0	0
CRKL	0.035	0.008	-10000	0	0	28	28
Rac1/GDP	0.017	0.02	-10000	0	-0.13	5	5
DOCK1	0.024	0.018	-10000	0	0	183	183
ITGA4	0.036	0.006	-10000	0	0	13	13
alpha4/beta7 Integrin/MAdCAM1	0.082	0.038	-10000	0	-0.12	6	6
EPO	0.025	0.017	-10000	0	0	164	164
alpha4/beta7 Integrin	0.052	0.012	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.035	0.008	-10000	0	0	23	23
alpha4/beta1 Integrin	0.038	0.025	-10000	0	-10000	0	0
EPO/EPOR (dimer)	0.036	0.026	-10000	0	-10000	0	0
lamellipodium assembly	-0.016	0.1	-10000	0	-0.38	22	22
PIK3CA	0.031	0.014	-10000	0	0	82	82
PI3K	0.018	0.076	-10000	0	-0.16	72	72
ARF6	0.035	0.009	-10000	0	0	29	29
JAK2	0.009	0.031	-10000	0	-10000	0	0
PXN	0.036	0.004	-10000	0	0	7	7
PIK3R1	0.032	0.012	-10000	0	0	63	63
MADCAM1	0.035	0.009	-10000	0	0	29	29
cell adhesion	0.079	0.037	-10000	0	-0.12	6	6
CRKL/CBL	0.051	0.014	-10000	0	-10000	0	0
ITGB1	0.026	0.017	-10000	0	0	144	144
SRC	-0.034	0.059	0.19	4	-10000	0	4
ITGB7	0.036	0.006	-10000	0	0	14	14
RAC1	0.025	0.017	-10000	0	0	163	163
alpha4/beta1 Integrin/VCAM1	0.002	0.078	-10000	0	-0.12	126	126
p130Cas/Crk/Dock1	-0.031	0.065	0.2	4	-0.2	7	11
VCAM1	0.023	0.018	-10000	0	0	195	195
RHOA	0.035	0.007	-10000	0	0	21	21
alpha4/beta1 Integrin/Paxillin/GIT1	0.062	0.05	-10000	0	-10000	0	0
BCAR1	-0.033	0.052	0.18	4	-10000	0	4
EPOR	0.035	0.008	-10000	0	0	25	25
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.036	0.005	-10000	0	0	8	8
GIT1	0.037	0.003	-10000	0	0	3	3
Rac1/GTP	-0.016	0.11	-10000	0	-0.39	22	22

×

IL1-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.025	0.019	-10000	0	-0.13	7	7
PRKCZ	0	0	-10000	0	-10000	0	0
MAP3K7IP2	0.033	0.011	-10000	0	0	47	47
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.01	0.12	-10000	0	-0.29	60	60
IRAK/TOLLIP	0.028	0.033	-10000	0	-0.12	22	22
IKBKB	0.036	0.003	-10000	0	0	4	4
IKBKG	0.037	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0.043	0.022	-10000	0	-10000	0	0
IL1A	0.035	0.007	-10000	0	0	22	22
IL1B	0.003	0.044	0.093	95	-10000	0	95
IRAK/TRAF6/p62/Atypical PKCs	0.053	0.052	-10000	0	-0.13	30	30
IL1R2	0.03	0.014	-10000	0	0	90	90
IL1R1	0.036	0.006	-10000	0	0	12	12
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.014	0.1	-10000	0	-0.29	40	40
TOLLIP	0.035	0.009	-10000	0	0	31	31
TICAM2	0	0	-10000	0	-10000	0	0
MAP3K3	0.036	0.005	-10000	0	0	8	8
TAK1/TAB1/TAB2	0.055	0.05	-10000	0	-0.15	21	21
IKK complex/ELKS	-0.046	0.097	-10000	0	-0.26	17	17
JUN	-0.039	0.042	0.15	2	-0.21	10	12
MAP3K7	0.034	0.01	-10000	0	0	43	43
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.031	0.11	-10000	0	-0.15	112	112
IL1 alpha/IL1R1/IL1RAP/MYD88	0.065	0.069	-10000	0	-0.13	49	49
PIK3R1	0.032	0.012	-10000	0	0	63	63
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.074	0.075	-10000	0	-0.13	48	48
IL1 beta fragment/IL1R1/IL1RAP	0.025	0.083	0.16	8	-0.14	83	91
NFKB1	0.035	0.007	-10000	0	0	18	18
MAPK8	-0.034	0.036	0.17	2	-0.2	8	10
IRAK1	-0.018	0.011	-10000	0	-0.12	5	5
IL1RN/IL1R1	0.053	0.01	-10000	0	-10000	0	0
IRAK4	0.035	0.007	-10000	0	0	19	19
PRKCI	0.035	0.008	-10000	0	0	27	27
TRAF6	0.036	0.005	-10000	0	0	10	10
PI3K	0.018	0.076	-10000	0	-0.16	72	72
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.008	0.12	-10000	0	-0.28	59	59
CHUK	0.025	0.017	-10000	0	0	165	165
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.025	0.083	0.16	8	-0.14	83	91
IL1 beta/IL1R2	0.017	0.072	-10000	0	-0.14	71	71
IRAK/TRAF6/TAK1/TAB1/TAB2	0.058	0.07	-10000	0	-0.14	36	36
NF kappa B1 p50/RelA	0.015	0.1	-10000	0	-0.15	107	107
IRAK3	0.035	0.008	-10000	0	0	27	27
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.038	0.083	-10000	0	-0.13	81	81
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.009	0.076	-10000	0	-0.28	15	15
IL1 alpha/IL1R1/IL1RAP	0.049	0.054	-10000	0	-0.13	33	33
RELA	0.036	0.004	-10000	0	0	7	7
MAP3K7IP1	0.034	0.009	-10000	0	0	36	36
SQSTM1	0.034	0.009	-10000	0	0	35	35
MYD88	0.034	0.009	-10000	0	0	36	36
IRAK/TRAF6/MEKK3	0.05	0.038	-10000	0	-0.12	22	22
IL1RAP	0.03	0.014	-10000	0	0	95	95
UBE2N	0.036	0.006	-10000	0	0	12	12
IRAK/TRAF6	-0.039	0.063	0.063	70	-0.2	24	94
CASP1	0.029	0.015	-10000	0	0	110	110
IL1RN/IL1R2	0.045	0.021	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.038	0.097	-10000	0	-0.15	91	91
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.002	0.1	-10000	0	-0.31	36	36
PIK3CA	0.031	0.014	-10000	0	0	82	82
IL1RN	0.036	0.004	-10000	0	0	6	6
TRAF6/TAK1/TAB1/TAB2	0.064	0.061	-10000	0	-0.14	24	24
MAP2K6	-0.039	0.034	0.17	3	-0.21	8	11

×

p38 MAPK signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.011	0.052	-10000	0	-0.12	47	47
TRAF2/ASK1	0.032	0.044	-10000	0	-0.12	36	36
ATM	0.034	0.01	-10000	0	0	37	37
MAP2K3	0.011	0.1	0.23	2	-0.3	29	31
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.009	0.093	0.23	2	-0.28	25	27
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.032	0.012	-10000	0	0	65	65
TXN	0.007	0.002	-10000	0	0	37	37
CALM1	0.033	0.012	-10000	0	0	57	57
GADD45A	0.031	0.013	-10000	0	0	77	77
GADD45B	0.031	0.014	-10000	0	0	84	84
MAP3K1	0.035	0.007	-10000	0	0	20	20
MAP3K6	0.035	0.007	-10000	0	0	22	22
MAP3K7	0.034	0.01	-10000	0	0	43	43
MAP3K4	0.032	0.012	-10000	0	0	65	65
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.032	0.054	-10000	0	-0.14	39	39
TAK1/TAB family	0.009	0.056	-10000	0	-0.33	11	11
RAC1/OSM/MEKK3	0.031	0.026	-10000	0	-0.1	5	5
TRAF2	0.036	0.006	-10000	0	0	16	16
RAC1/OSM/MEKK3/MKK3	0.011	0.078	-10000	0	-0.26	23	23
TRAF6	0.009	0.033	-10000	0	-0.2	12	12
RAC1	0.025	0.017	-10000	0	0	163	163
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.017	0.018	-10000	0	0	275	275
CCM2	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.008	0.056	-10000	0	-0.14	53	53
MAPK11	0.033	0.011	-10000	0	0	54	54
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.009	0.069	-10000	0	-0.14	67	67
OSM/MEKK3	0.027	0.003	-10000	0	-10000	0	0
TAOK1	0.007	0.002	-10000	0	0	37	37
TAOK2	0.012	0.024	-10000	0	-0.2	6	6
TAOK3	0.006	0.041	-10000	0	-0.2	19	19
MAP3K7IP1	0.034	0.009	-10000	0	0	36	36
MAPK14	0.036	0.004	-10000	0	0	5	5
MAP3K7IP2	0.033	0.011	-10000	0	0	47	47
MAP3K5	0.03	0.014	-10000	0	0	90	90
MAP3K10	0.035	0.008	-10000	0	0	28	28
MAP3K3	0.036	0.005	-10000	0	0	8	8
TRX/ASK1	0.023	0.035	-10000	0	-0.17	13	13
GADD45/MTK1/MTK1	0.044	0.077	-10000	0	-0.13	66	66

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.052	0.056	-10000	0	-0.13	35	35
fibroblast growth factor receptor signaling pathway	0.051	0.056	-10000	0	-0.13	35	35
LAMA1	0	0	-10000	0	-10000	0	0
PRNP	0.031	0.013	-10000	0	0	74	74
GPC1/SLIT2	0.032	0.046	-10000	0	-0.14	24	24
SMAD2	-0.023	0.049	0.18	11	-0.2	3	14
GPC1/PrPc/Cu2+	0.024	0.058	-10000	0	-0.14	50	50
GPC1/Laminin alpha1	0.015	0.04	-10000	0	-0.13	34	34
TDGF1	0.035	0.007	-10000	0	0	18	18
CRIPTO/GPC1	0.038	0.047	-10000	0	-0.14	28	28
APP/GPC1	0.034	0.058	-10000	0	-0.16	37	37
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.023	0.033	0.09	22	-0.13	23	45
FLT1	0.034	0.009	-10000	0	0	34	34
GPC1/TGFB/TGFBR1/TGFBR2	0.052	0.053	-10000	0	-0.12	33	33
SERPINC1	0.036	0.006	-10000	0	0	12	12
FYN	-0.018	0.029	0.09	24	-0.13	8	32
FGR	-0.022	0.033	0.09	22	-0.13	21	43
positive regulation of MAPKKK cascade	-0.031	0.13	0.19	22	-0.3	60	82
SLIT2	0.029	0.015	-10000	0	0	102	102
GPC1/NRG	0.037	0.051	-10000	0	-0.14	34	34
NRG1	0.036	0.005	-10000	0	0	9	9
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.032	0.043	-10000	0	-0.12	34	34
LYN	-0.022	0.034	0.09	22	-0.13	23	45
mol:Spermine	-0.01	0.004	-10000	0	-10000	0	0
cell growth	0.051	0.056	-10000	0	-0.13	35	35
BMP signaling pathway	-0.032	0.012	0	64	-10000	0	64
SRC	-0.024	0.035	0.09	23	-0.13	27	50
TGFBR1	0.036	0.006	-10000	0	0	16	16
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	0.018	0.018	-10000	0	0	264	264
GPC1	0.032	0.012	-10000	0	0	64	64
TGFBR1 (dimer)	0.036	0.006	-10000	0	0	16	16
VEGFA	0	0	-10000	0	-10000	0	0
BLK	-0.025	0.035	0.09	24	-0.13	26	50
HCK	-0.018	0.031	0.09	19	-0.13	16	35
FGF2	0.035	0.008	-10000	0	0	25	25
FGFR1	0.036	0.005	-10000	0	0	9	9
VEGFR1 homodimer	0.034	0.009	-10000	0	0	34	34
TGFBR2	0.035	0.009	-10000	0	0	29	29
cell death	0.034	0.058	-10000	0	-0.16	37	37
ATIII/GPC1	0.038	0.049	-10000	0	-0.14	31	31
PLA2G2A/GPC1	-0.005	0.075	-10000	0	-0.15	92	92
LCK	-0.024	0.034	0.09	24	-0.13	24	48
neuron differentiation	0.037	0.051	-10000	0	-0.14	34	34
PrPc/Cu2+	0.015	0.038	-10000	0	-0.13	30	30
APP	0.035	0.007	-10000	0	0	20	20
TGFBR2 (dimer)	0.035	0.009	-10000	0	0	29	29

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.001	0.009	0.024	2	-0.032	18	20
BUB1B	-0.022	0.085	0.12	21	-0.23	60	81
PLK1	0.004	0.023	0.081	19	-0.068	5	24
PLK1S1	0.003	0.014	0.048	22	-0.038	3	25
KIF2A	0.005	0.021	0.071	19	-0.061	5	24
regulation of mitotic centrosome separation	0.005	0.023	0.081	19	-0.068	5	24
GOLGA2	0.035	0.008	-10000	0	0	27	27
Hec1/SPC24	-0.004	0.01	-10000	0	-0.054	7	7
WEE1	-0.031	0.13	-10000	0	-0.45	37	37
cytokinesis	-0.022	0.11	0.15	13	-0.3	61	74
PP2A-alpha B56	0.054	0.078	-10000	0	-0.51	6	6
AURKA	0.003	0.016	0.055	22	-0.04	3	25
PICH/PLK1	-0.034	0.075	0.071	10	-0.18	89	99
CENPE	0.004	0.049	0.15	30	-0.11	6	36
RhoA/GTP	0.024	0.019	-10000	0	-0.13	7	7
positive regulation of microtubule depolymerization	0.005	0.021	0.071	19	-0.06	5	24
PPP2CA	0.035	0.007	-10000	0	0	20	20
FZR1	0.035	0.008	-10000	0	0	25	25
TPX2	-0.026	0.089	0.12	1	-0.22	85	86
PAK1	0.036	0.007	-10000	0	0	16	16
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	0.035	0.007	-10000	0	0	22	22
CLSPN	0.01	0.027	-10000	0	-0.2	6	6
GORASP1	0.034	0.009	-10000	0	0	33	33
metaphase	0.001	0.003	0.016	9	-0.011	2	11
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.003	0.014	0.048	22	-0.038	3	25
G2 phase of mitotic cell cycle	-0.001	0.002	0.01	7	-10000	0	7
STAG2	0.035	0.007	-10000	0	0	22	22
GRASP65/GM130/RAB1/GTP	-0.02	0.14	-10000	0	-0.6	26	26
spindle elongation	0.005	0.023	0.081	19	-0.068	5	24
ODF2	0.035	0.009	-10000	0	0	29	29
BUB1	0.021	0.063	-10000	0	-0.56	5	5
TPT1	-0.003	0.052	-10000	0	-0.18	38	38
CDC25C	0.013	0.026	-10000	0	-0.22	5	5
CDC25B	0.012	0.031	-10000	0	-0.029	167	167
SGOL1	0.001	0.009	0.032	18	-0.024	2	20
RHOA	0.035	0.007	-10000	0	0	21	21
CCNB1/CDK1	-0.022	0.13	-10000	0	-0.23	103	103
CDC14B	-0.011	0.004	0.01	8	-10000	0	8
CDC20	0.028	0.016	-10000	0	0	127	127
PLK1/PBIP1	-0.015	0.037	0.07	8	-0.091	78	86
mitosis	-0.001	0.003	0.012	10	-10000	0	10
FBXO5	-0.016	0.063	0.12	17	-0.17	51	68
CDC2	0.015	0.023	-10000	0	-0.031	41	41
NDC80	0	0	-10000	0	-10000	0	0
metaphase plate congression	0.002	0.06	-10000	0	-0.26	24	24
ERCC6L	-0.045	0.1	-10000	0	-0.22	98	98
NLP/gamma Tubulin	0.002	0.028	0.075	11	-0.1	21	32
microtubule cytoskeleton organization	-0.003	0.052	-10000	0	-0.18	38	38
G2/M transition DNA damage checkpoint	-0.001	0.002	0.01	6	-10000	0	6
PPP1R12A	0.035	0.008	-10000	0	0	22	22
interphase	-0.001	0.002	0.01	6	-10000	0	6
PLK1/PRC1-2	0.007	0.077	0.13	1	-0.14	91	92
GRASP65/GM130/RAB1/GTP/PLK1	0.048	0.053	-10000	0	-0.12	29	29
RAB1A	0.035	0.007	-10000	0	0	19	19
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.003	0.018	0.064	21	-0.048	2	23
mitotic prometaphase	0	0.005	0.02	24	-10000	0	24
proteasomal ubiquitin-dependent protein catabolic process	-0.05	0.1	0.18	2	-0.21	124	126
microtubule-based process	0.02	0.025	0.098	6	-0.063	5	11
Golgi organization	0.005	0.023	0.081	19	-0.068	5	24
Cohesin/SA2	0.021	0.033	0.096	6	-0.096	21	27
PPP1CB/MYPT1	0.047	0.036	-10000	0	-0.16	14	14
KIF20A	0.029	0.015	-10000	0	0	110	110
APC/C/CDC20	0.02	0.025	0.11	5	-0.061	3	8
PPP2R1A	0.032	0.012	-10000	0	0	59	59
chromosome segregation	-0.014	0.036	0.069	8	-0.089	78	86
PRC1	0.028	0.016	-10000	0	0	122	122
ECT2	0.002	0.061	0.17	33	-0.13	5	38
C13orf34	0.004	0.02	0.067	20	-0.055	3	23
NUDC	0.002	0.06	-10000	0	-0.26	24	24
regulation of attachment of spindle microtubules to kinetochore	-0.021	0.085	0.12	21	-0.22	60	81
spindle assembly	0.002	0.026	0.083	16	-0.078	14	30
spindle stabilization	0.003	0.014	0.048	22	-0.038	3	25
APC/C/HCDH1	0.024	0.026	0.09	1	-0.12	15	16
MKLP2/PLK1	0.02	0.025	0.098	6	-0.064	5	11
CCNB1	0.015	0.027	-10000	0	-0.028	108	108
PPP1CB	0.036	0.006	-10000	0	0	14	14
BTRC	0.026	0.017	-10000	0	0	155	155
ROCK2	0.017	0.03	-10000	0	-0.2	4	4
TUBG1	0.002	0.05	-10000	0	-0.22	22	22
G2/M transition of mitotic cell cycle	-0.047	0.11	0.14	17	-0.23	94	111
MLF1IP	-0.009	0.006	0.01	2	-10000	0	2
INCENP	0.036	0.004	-10000	0	0	6	6

×

FAS signaling pathway (CD95)

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
SPTAN1	-0.018	0.056	0.22	7	-0.21	21	28
RFC1	-0.02	0.048	0.18	2	-0.21	25	27
PRKDC	-0.017	0.055	0.19	7	-0.21	24	31
RIPK1	0.028	0.021	-10000	0	-0.023	73	73
CASP7	-0.17	0.29	-10000	0	-0.58	164	164
FASLG/FAS/FADD/FAF1	-0.016	0.087	0.16	28	-0.18	44	72
MAP2K4	-0.046	0.14	0.22	2	-0.33	39	41
mol:ceramide	0.002	0.094	0.19	5	-0.25	20	25
GSN	-0.008	0.058	0.19	11	-0.21	19	30
FASLG/FAS/FADD/FAF1/Caspase 8	-0.014	0.097	0.19	8	-0.26	24	32
FAS	0.021	0.02	-10000	0	-10000	0	0
BID	-0.032	0.034	-10000	0	-0.13	23	23
MAP3K1	-0.1	0.19	-10000	0	-0.37	164	164
MAP3K7	0.035	0.011	-10000	0	0	43	43
RB1	-0.017	0.045	0.23	1	-0.21	23	24
CFLAR	0.029	0.021	-10000	0	-0.028	60	60
HGF/MET	0.035	0.049	-10000	0	-0.13	21	21
ARHGDIB	-0.015	0.056	0.22	7	-0.22	21	28
FADD	0.038	0.007	-10000	0	-10000	0	0
actin filament polymerization	0.008	0.058	0.21	19	-0.19	11	30
NFKB1	0.029	0.11	-10000	0	-0.65	10	10
MAPK8	-0.036	0.14	0.24	1	-0.37	21	22
DFFA	-0.017	0.048	0.22	3	-0.21	24	27
DNA fragmentation during apoptosis	-0.016	0.046	0.22	2	-0.2	24	26
FAS/FADD/MET	0.025	0.053	-10000	0	-0.12	28	28
CFLAR/RIP1	0.048	0.02	-10000	0	-0.065	9	9
FAIM3	0.034	0.009	-10000	0	0	35	35
FAF1	0.038	0.011	-10000	0	-10000	0	0
PARP1	-0.019	0.048	0.22	1	-0.21	26	27
DFFB	-0.016	0.045	0.22	2	-0.2	23	25
CHUK	0.016	0.099	-10000	0	-0.61	10	10
FASLG	0.039	0.008	-10000	0	-10000	0	0
FAS/FADD	0.021	0.054	-10000	0	-0.15	36	36
HGF	0.024	0.018	-10000	0	0	177	177
LMNA	-0.02	0.049	0.2	5	-0.19	24	29
CASP6	-0.017	0.046	0.17	3	-0.2	24	27
CASP10	0.039	0.004	-10000	0	-10000	0	0
CASP3	-0.011	0.05	-10000	0	-0.22	25	25
PTPN13	0.032	0.012	-10000	0	0	60	60
CASP8	-0.029	0.014	0.085	4	-10000	0	4
IL6	0.02	0.13	-10000	0	-0.66	5	5
MET	0.023	0.018	-10000	0	0	190	190
ICAD/CAD	-0.021	0.049	0.25	4	-0.2	23	27
FASLG/FAS/FADD/FAF1/Caspase 10	0.002	0.095	0.19	5	-0.25	20	25
activation of caspase activity by cytochrome c	-0.031	0.033	-10000	0	-0.13	23	23
PAK2	-0.015	0.049	0.15	2	-0.2	25	27
BCL2	0.035	0.007	-10000	0	0	20	20

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.008	0.059	-10000	0	-0.22	25	25
epithelial cell differentiation	0.064	0.052	-10000	0	-0.14	25	25
CYFIP2	0.031	0.013	-10000	0	0	76	76
ENAH	-0.042	0.072	0.24	12	-0.24	11	23
EGFR	0.009	0.016	-10000	0	0	379	379
EPHA2	0.033	0.011	-10000	0	0	55	55
MYO6	-0.029	0.05	0.18	9	-0.22	13	22
CTNNB1	0.036	0.006	-10000	0	0	15	15
ABI1/Sra1/Nap1	0.029	0.065	-10000	0	-0.12	60	60
AQP5	-0.021	0.053	0.19	3	-0.29	10	13
CTNND1	0.035	0.009	-10000	0	0	31	31
mol:PI-4-5-P2	-0.031	0.045	0.17	7	-0.21	13	20
regulation of calcium-dependent cell-cell adhesion	-0.028	0.044	0.18	8	-0.19	8	16
EGF	0.035	0.008	-10000	0	0	25	25
NCKAP1	0.037	0.002	-10000	0	0	2	2
AQP3	-0.034	0.075	-10000	0	-0.3	31	31
cortical microtubule organization	0.064	0.052	-10000	0	-0.14	25	25
GO:0000145	-0.03	0.041	0.16	7	-0.2	13	20
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.071	0.054	-10000	0	-0.14	25	25
MLLT4	0.034	0.009	-10000	0	0	34	34
ARF6/GDP	-0.053	0.04	-10000	0	-0.22	13	13
ARF6	0.035	0.009	-10000	0	0	29	29
Ephrin A1/EPHA2/NCK1/GIT1	0.075	0.055	-10000	0	-0.13	25	25
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.031	0.087	0.16	1	-0.3	36	37
PVRL2	0.034	0.009	-10000	0	0	35	35
ZYX	-0.022	0.045	0.18	6	-0.22	15	21
ARF6/GTP	0.079	0.061	-10000	0	-0.13	24	24
CDH1	0.034	0.01	-10000	0	0	37	37
EGFR/EGFR/EGF/EGF	-0.001	0.06	-10000	0	-0.13	67	67
RhoA/GDP	0.064	0.057	-10000	0	-0.14	29	29
actin cytoskeleton organization	-0.024	0.047	0.16	7	-0.23	12	19
IGF-1R heterotetramer	0.033	0.011	-10000	0	0	53	53
GIT1	0.037	0.003	-10000	0	0	3	3
IGF1R	0.033	0.011	-10000	0	0	53	53
IGF1	0.035	0.007	-10000	0	0	21	21
DIAPH1	-0.13	0.28	-10000	0	-0.51	156	156
Wnt receptor signaling pathway	-0.064	0.052	0.14	25	-10000	0	25
RHOA	0.035	0.007	-10000	0	0	21	21
RhoA/GTP	-0.054	0.042	-10000	0	-0.21	17	17
CTNNA1	0.035	0.007	-10000	0	0	18	18
VCL	-0.024	0.048	0.17	7	-0.23	12	19
EFNA1	0.033	0.011	-10000	0	0	52	52
LPP	-0.03	0.048	0.18	4	-0.24	13	17
Ephrin A1/EPHA2	0.046	0.063	-10000	0	-0.14	41	41
SEC6/SEC8	-0.044	0.029	-10000	0	-0.14	26	26
MGAT3	-0.028	0.045	0.18	8	-0.2	8	16
HGF/MET	0.037	0.048	-10000	0	-0.14	15	15
HGF	0.024	0.018	-10000	0	0	177	177
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.008	0.06	-10000	0	-0.22	25	25
actin cable formation	-0.04	0.1	0.31	10	-0.3	33	43
KIAA1543	-0.025	0.037	0.16	7	-0.18	8	15
KIFC3	-0.031	0.042	0.19	5	-0.2	8	13
NCK1	0.035	0.008	-10000	0	0	27	27
EXOC3	0.036	0.003	-10000	0	0	4	4
ACTN1	-0.027	0.051	0.19	7	-0.22	16	23
NCK1/GIT1	0.05	0.024	-10000	0	-0.14	6	6
mol:GDP	0.064	0.052	-10000	0	-0.14	25	25
EXOC4	0	0	-10000	0	-10000	0	0
STX4	-0.028	0.031	0.053	22	-0.13	25	47
PIP5K1C	-0.031	0.046	0.18	7	-0.21	13	20
LIMA1	0	0	-10000	0	-10000	0	0
ABI1	0.025	0.017	-10000	0	0	158	158
ROCK1	-0.035	0.086	0.3	15	-0.28	6	21
adherens junction assembly	-0.024	0.072	0.22	6	-0.33	14	20
IGF-1R heterotetramer/IGF1	0.05	0.062	-10000	0	-0.15	37	37
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.047	0.023	-10000	0	-0.14	3	3
MET	0.023	0.018	-10000	0	0	190	190
PLEKHA7	-0.028	0.031	0.053	22	-0.13	25	47
mol:GTP	0.072	0.053	-10000	0	-0.13	25	25
establishment of epithelial cell apical/basal polarity	-0.039	0.039	0.12	12	-0.19	10	22
cortical actin cytoskeleton stabilization	0.008	0.059	-10000	0	-0.22	25	25
regulation of cell-cell adhesion	-0.024	0.047	0.16	7	-0.23	12	19
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.008	0.06	-10000	0	-0.22	25	25

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	-0.017	0.021	0.093	16	-10000	0	16
BAD/BCL-XL/YWHAZ	0.047	0.034	-10000	0	-0.13	11	11
CDKN1B	-0.024	0.12	0.2	5	-0.33	57	62
CDKN1A	-0.027	0.12	-10000	0	-0.33	60	60
FRAP1	0.036	0.006	-10000	0	0	16	16
PRKDC	0.034	0.01	-10000	0	0	45	45
FOXO3	-0.018	0.11	-10000	0	-0.31	61	61
AKT1	-0.018	0.12	-10000	0	-0.33	58	58
BAD	0.036	0.006	-10000	0	0	13	13
AKT3	0.015	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	-0.018	0.11	-10000	0	-0.31	61	61
AKT1/ASK1	-0.009	0.13	0.25	1	-0.32	60	61
BAD/YWHAZ	0.064	0.037	-10000	0	-0.13	12	12
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	0.035	0.008	-10000	0	0	28	28
JNK cascade	0.009	0.12	0.31	61	-0.24	1	62
TSC1	-0.025	0.12	0.2	1	-0.33	59	60
YWHAZ	0.035	0.007	-10000	0	0	21	21
AKT1/RAF1	0	0.13	0.26	1	-0.33	62	63
EP300	0.033	0.011	-10000	0	0	50	50
mol:GDP	-0.018	0.12	-10000	0	-0.32	60	60
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	-0.026	0.12	-10000	0	-0.33	62	62
YWHAQ	0.036	0.005	-10000	0	0	8	8
TBC1D4	-0.001	0.022	0.12	14	-10000	0	14
MAP3K5	0.03	0.014	-10000	0	0	90	90
MAPKAP1	0.034	0.009	-10000	0	0	32	32
negative regulation of cell cycle	0.003	0.11	0.36	24	-10000	0	24
YWHAH	0.031	0.013	-10000	0	0	73	73
AKT1S1	-0.018	0.11	-10000	0	-0.31	61	61
CASP9	-0.02	0.12	0.2	3	-0.32	59	62
YWHAB	0.034	0.01	-10000	0	0	41	41
p27Kip1/KPNA1	-0.006	0.13	0.29	4	-0.32	60	64
GBL	0.036	0.006	-10000	0	0	15	15
PDK1/Src/Hsp90	0.046	0.014	-10000	0	-10000	0	0
YWHAE	0.035	0.008	-10000	0	0	27	27
SRC	0.034	0.009	-10000	0	0	34	34
AKT2/p21CIP1	-0.024	0.11	0.23	1	-0.28	61	62
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.016	0.07	-10000	0	-0.46	7	7
CHUK	-0.022	0.1	-10000	0	-0.33	47	47
BAD/BCL-XL	0.003	0.12	-10000	0	-0.32	56	56
mTORC2	0.06	0.032	-10000	0	-0.12	9	9
AKT2	0.014	0.004	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	-0.005	0.13	-10000	0	-0.42	28	28
PDPK1	0.036	0.005	-10000	0	0	8	8
MDM2	-0.016	0.12	0.2	10	-0.32	58	68
MAPKKK cascade	0	0.13	0.33	62	-0.26	1	63
MDM2/Cbp/p300	0.015	0.13	0.27	1	-0.31	59	60
TSC1/TSC2	-0.029	0.13	0.26	8	-0.34	62	70
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.12	0.26	1	-0.3	59	60
glucose import	-0.008	0.022	0.2	3	-10000	0	3
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.013	0.084	-10000	0	-0.34	10	10
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.008	0.022	0.2	3	-10000	0	3
GSK3A	-0.019	0.12	0.25	8	-0.32	57	65
FOXO1	-0.018	0.11	-10000	0	-0.31	61	61
GSK3B	-0.024	0.12	0.2	4	-0.34	60	64
SFN	0.031	0.013	-10000	0	0	80	80
G1/S transition of mitotic cell cycle	-0.028	0.13	0.25	9	-0.33	62	71
p27Kip1/14-3-3 family	0.011	0.11	-10000	0	-0.55	12	12
PRKACA	0.035	0.008	-10000	0	0	24	24
KPNA1	0.035	0.008	-10000	0	0	24	24
HSP90AA1	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0.025	0.017	-10000	0	0	167	167
CREBBP	0.036	0.005	-10000	0	0	9	9

×

S1P1 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
VEGFR2 homodimer/VEGFA homodimer	0.017	0.052	-10000	0	-0.19	28	28
PDGFRB	0.036	0.009	-10000	0	-0.001	27	27
SPHK1	0.016	0.04	-10000	0	-0.76	1	1
mol:S1P	0.018	0.042	-10000	0	-0.68	1	1
S1P1/S1P/Gi	-0.001	0.14	0.25	15	-0.47	27	42
GNAO1	0.033	0.015	0.064	1	0	87	88
PDGFB-D/PDGFRB/PLCgamma1	0.03	0.15	0.25	33	-0.4	28	61
PLCG1	-0.004	0.13	0.23	22	-0.43	27	49
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.036	0.009	-10000	0	-0.001	27	27
GNAI2	0.036	0.012	-10000	0	0	44	44
GNAI3	0.038	0.007	-10000	0	0	14	14
GNAI1	0.019	0.02	-10000	0	0	262	262
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	0.009	0.076	0.12	11	-0.28	28	39
S1P1/S1P	0.025	0.08	0.22	3	-0.3	15	18
negative regulation of cAMP metabolic process	0	0.14	0.24	15	-0.46	27	42
MAPK3	0.001	0.14	0.28	18	-0.46	25	43
calcium-dependent phospholipase C activity	0	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.017	0.02	-10000	0	-0.13	5	5
RhoA/GDP	0.024	0.019	-10000	0	-0.13	7	7
KDR	0.027	0.035	0.094	1	-0.13	18	19
PLCB2	0.038	0.092	0.23	20	-0.28	15	35
RAC1	0.025	0.017	-10000	0	0	163	163
RhoA/GTP	0.017	0.068	-10000	0	-0.25	18	18
receptor internalization	0.024	0.076	0.21	3	-0.28	15	18
PTGS2	0.033	0.15	0.36	7	-0.47	15	22
Rac1/GTP	0.009	0.059	-10000	0	-0.28	12	12
RHOA	0.035	0.007	-10000	0	0	21	21
VEGFA	-0.001	0.022	-10000	0	-0.1	23	23
negative regulation of T cell proliferation	0	0.14	0.24	15	-0.46	27	42
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.033	0.015	-10000	0	0	80	80
MAPK1	0.004	0.14	0.29	15	-0.48	22	37
S1P1/S1P/PDGFB-D/PDGFRB	0.055	0.11	0.25	15	-0.3	20	35
ABCC1	0.037	0.008	-10000	0	0	19	19

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.033	0.11	0.3	18	-0.3	22	40
PDGFB-D/PDGFRB/SLAP	0.017	0.075	-10000	0	-0.16	72	72
PDGFB-D/PDGFRB/APS/CBL	0.045	0.024	-10000	0	-0.12	8	8
AKT1	-0.024	0.092	0.26	14	-0.24	16	30
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.025	0.11	0.28	16	-0.32	21	37
PIK3CA	0.031	0.014	-10000	0	0	82	82
FGR	0.005	0.1	0.24	3	-0.46	15	18
mol:Ca2+	0.017	0.1	0.25	18	-0.35	20	38
MYC	0.01	0.26	0.37	40	-0.66	54	94
SHC1	0.033	0.011	-10000	0	0	52	52
HRAS/GDP	0.015	0.07	0.18	36	-0.16	21	57
LRP1/PDGFRB/PDGFB	0.048	0.057	-10000	0	-0.14	32	32
GRB10	0.021	0.018	-10000	0	0	222	222
PTPN11	0.036	0.005	-10000	0	0	11	11
GO:0007205	0.016	0.1	0.25	18	-0.36	20	38
PTEN	0.025	0.017	-10000	0	0	168	168
GRB2	0.035	0.007	-10000	0	0	18	18
GRB7	0.036	0.006	-10000	0	0	15	15
PDGFB-D/PDGFRB/SHP2	0.047	0.035	-10000	0	-0.15	14	14
PDGFB-D/PDGFRB/GRB10	0.02	0.052	-10000	0	-0.15	32	32
cell cycle arrest	0.017	0.075	-10000	0	-0.16	72	72
HRAS	0.034	0.009	-10000	0	0	36	36
HIF1A	-0.029	0.084	0.23	14	-0.25	16	30
GAB1	0.012	0.13	0.29	13	-0.37	29	42
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.011	0.12	0.32	17	-0.33	28	45
PDGFB-D/PDGFRB	0.054	0.054	-10000	0	-0.1	24	24
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.044	0.042	-10000	0	-0.15	21	21
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.023	0.12	0.27	5	-0.29	34	39
positive regulation of MAPKKK cascade	0.047	0.035	-10000	0	-0.15	14	14
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	0.017	0.11	0.25	18	-0.36	20	38
E5	-0.001	0.001	-10000	0	-10000	0	0
CSK	0.034	0.011	-10000	0	-0.01	26	26
PDGFB-D/PDGFRB/GRB7	0.05	0.024	-10000	0	-0.14	5	5
SHB	0.033	0.011	-10000	0	0	51	51
BLK	0.014	0.078	0.24	2	-0.43	7	9
PTPN2	0.033	0.018	0.07	1	-0.02	49	50
PDGFB-D/PDGFRB/SNX15	0.05	0.027	-10000	0	-0.14	8	8
BCAR1	0	0	-10000	0	-10000	0	0
VAV2	0	0.16	0.3	17	-0.39	48	65
CBL	0.036	0.005	-10000	0	0	8	8
PDGFB-D/PDGFRB/DEP1	0.049	0.028	-10000	0	-0.14	8	8
LCK	0.018	0.063	0.24	2	-0.36	3	5
PDGFRB	0.031	0.022	0.07	2	-0.019	73	75
ACP1	0.035	0.007	-10000	0	0	18	18
HCK	-0.042	0.18	-10000	0	-0.5	59	59
ABL1	0.007	0.12	0.25	20	-0.33	30	50
PDGFB-D/PDGFRB/CBL	0.011	0.13	0.32	8	-0.41	27	35
PTPN1	0.03	0.019	-10000	0	-0.013	75	75
SNX15	0.036	0.003	-10000	0	0	4	4
STAT3	0.034	0.01	-10000	0	0	37	37
STAT1	0.034	0.01	-10000	0	0	40	40
cell proliferation	0.017	0.24	0.35	43	-0.59	55	98
SLA	0.027	0.016	-10000	0	0	133	133
actin cytoskeleton reorganization	-0.016	0.071	0.19	38	-0.2	7	45
SRC	0.014	0.047	0.22	1	-10000	0	1
PI3K	-0.047	0.045	-10000	0	-0.16	46	46
PDGFB-D/PDGFRB/GRB7/SHC	0.061	0.038	-10000	0	-0.13	11	11
SH2B2	0	0	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.025	0.11	0.29	16	-0.33	21	37
LYN	-0.035	0.16	0.22	1	-0.47	54	55
LRP1	0.032	0.013	-10000	0	0	70	70
SOS1	0	0	-10000	0	-10000	0	0
STAT5B	0.036	0.004	-10000	0	0	5	5
STAT5A	0.036	0.004	-10000	0	0	5	5
NCK1-2/p130 Cas	0.064	0.067	-10000	0	-0.14	26	26
SPHK1	0.034	0.012	0.061	3	0	51	54
EDG1	0.034	0.011	0.061	3	0	45	48
mol:DAG	0.017	0.11	0.25	18	-0.36	20	38
PLCG1	0.016	0.11	0.27	13	-0.37	20	33
NHERF/PDGFRB	0.063	0.037	-10000	0	-0.13	12	12
YES1	-0.005	0.13	0.23	2	-0.54	22	24
cell migration	0.062	0.037	-10000	0	-0.13	12	12
SHC/Grb2/SOS1	0.066	0.062	-10000	0	-0.14	21	21
SLC9A3R2	0.036	0.005	-10000	0	0	8	8
SLC9A3R1	0.034	0.009	-10000	0	0	36	36
NHERF1-2/PDGFRB/PTEN	0.055	0.056	-10000	0	-0.11	13	13
FYN	-0.052	0.19	-10000	0	-0.45	78	78
DOK1	-0.013	0.06	0.17	38	-0.13	4	42
HRAS/GTP	0.021	0.028	-10000	0	-0.13	16	16
PDGFB	0.034	0.01	-10000	0	0	38	38
RAC1	0.032	0.19	0.34	46	-0.43	50	96
PRKCD	-0.009	0.063	0.18	39	-0.14	3	42
FER	-0.011	0.063	0.18	38	-0.14	4	42
MAPKKK cascade	-0.009	0.068	0.16	49	-0.18	5	54
RASA1	-0.01	0.064	0.18	38	-0.17	6	44
NCK1	0.035	0.008	-10000	0	0	27	27
NCK2	0.036	0.007	-10000	0	0	17	17
p62DOK/Csk	-0.01	0.066	0.17	39	-0.2	3	42
PDGFB-D/PDGFRB/SHB	0.045	0.028	-10000	0	-0.14	6	6
chemotaxis	0.008	0.12	0.25	20	-0.32	30	50
STAT1-3-5/STAT1-3-5	0.06	0.073	-10000	0	-0.14	40	40
Bovine Papilomavirus E5/PDGFRB	0.02	0.026	-10000	0	-0.14	8	8
PTPRJ	0.036	0.005	-10000	0	0	11	11

×

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

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
MET/RANBP9	0.031	0.034	-10000	0	-0.14	8	8
CRKL	0.048	0.11	0.28	7	-0.4	16	23
mol:PIP3	0	0.054	-10000	0	-0.85	1	1
AKT1	-0.012	0.054	-10000	0	-0.75	1	1
PTK2B	0.036	0.006	-10000	0	0	16	16
RAPGEF1	0.045	0.1	0.29	10	-0.38	16	26
RANBP10	0.036	0.005	-10000	0	0	8	8
PIK3CA	0.031	0.014	-10000	0	0	82	82
HGF/MET/SHIP2	0.043	0.038	-10000	0	-0.13	2	2
MAP3K5	0.044	0.11	0.28	6	-0.37	17	23
HGF/MET/CIN85/CBL/ENDOPHILINS	0.041	0.035	-10000	0	-10000	0	0
AP1	0.033	0.081	0.15	100	-0.15	46	146
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.033	0.011	-10000	0	0	52	52
apoptosis	-0.12	0.36	-10000	0	-0.78	113	113
STAT3 (dimer)	0.012	0.058	-10000	0	-0.27	10	10
GAB1/CRKL/SHP2/PI3K	0.064	0.12	0.31	2	-0.39	18	20
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.064	0.11	0.28	4	-0.39	16	20
PTPN11	0.036	0.005	-10000	0	0	11	11
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.034	0.01	-10000	0	0	37	37
PTEN	0.025	0.017	-10000	0	0	168	168
ELK1	0.11	0.18	0.35	179	-10000	0	179
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.012	0.032	0.16	1	-0.14	12	13
PAK1	-0.017	0.053	-10000	0	-0.72	1	1
HGF/MET/RANBP10	0.043	0.037	-10000	0	-10000	0	0
HRAS	0.012	0.081	-10000	0	-0.47	10	10
DOCK1	0.036	0.1	0.26	9	-0.39	16	25
GAB1	0.047	0.1	-10000	0	-0.41	16	16
CRK	0.048	0.11	0.28	4	-0.4	16	20
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0.066	-10000	0	-0.42	9	9
JUN	0.034	0.01	-10000	0	0	41	41
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.009	0.018	-10000	0	-0.12	1	1
PIK3R1	0.032	0.012	-10000	0	0	63	63
cell morphogenesis	0.031	0.11	0.26	31	-0.31	14	45
GRB2/SHC	0.075	0.065	0.17	106	-0.12	2	108
FOS	0.025	0.017	-10000	0	0	162	162
GLMN	0.003	0.012	0.069	2	-0.17	2	4
cell motility	0.11	0.18	0.35	179	-10000	0	179
HGF/MET/MUC20	0.029	0.024	-10000	0	-10000	0	0
cell migration	0.073	0.063	0.17	106	-0.12	2	108
GRB2	0.035	0.007	-10000	0	0	18	18
CBL	0.036	0.005	-10000	0	0	8	8
MET/RANBP10	0.034	0.027	-10000	0	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.015	0.046	-10000	0	-0.18	18	18
MET/MUC20	0.017	0.013	-10000	0	-10000	0	0
RAP1B	0.045	0.099	0.27	11	-0.36	16	27
RAP1A	0.039	0.1	0.28	10	-0.36	15	25
HGF/MET/RANBP9	0.041	0.041	-10000	0	-0.12	7	7
RAF1	0.039	0.1	0.28	2	-0.44	13	15
STAT3	0.009	0.054	-10000	0	-0.29	9	9
cell proliferation	0.038	0.079	0.24	13	-0.27	8	21
RPS6KB1	0.014	0.018	-10000	0	-10000	0	0
MAPK3	0.08	0.16	0.33	127	-10000	0	127
MAPK1	0.11	0.21	0.4	146	-10000	0	146
RANBP9	0.036	0.006	-10000	0	0	16	16
MAPK8	-0.047	0.16	0.27	1	-0.34	65	66
SRC	0.008	0.044	-10000	0	-0.18	17	17
PI3K	0.058	0.074	0.17	90	-0.16	8	98
MET/Glomulin	0.015	0.028	-10000	0	-0.087	21	21
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	0.029	0.1	0.26	2	-0.42	14	16
MET	0.023	0.018	-10000	0	0	190	190
MAP4K1	0.053	0.11	0.3	4	-0.37	16	20
PTK2	0.034	0.009	-10000	0	0	34	34
MAP2K2	0.037	0.1	0.3	13	-0.4	13	26
BAD	-0.019	0.053	-10000	0	-0.72	1	1
MAP2K4	0.037	0.1	0.27	9	-0.34	17	26
SHP2/GRB2/SOS1/GAB1	0.021	0.077	-10000	0	-0.34	17	17
INPPL1	0.036	0.006	-10000	0	0	13	13
PXN	0.036	0.004	-10000	0	0	7	7
SH3KBP1	0	0	-10000	0	-10000	0	0
HGS	0.001	0.018	0.082	3	-0.12	1	4
PLCgamma1/PKC	0.024	0.014	-10000	0	-0.13	3	3
HGF	0.024	0.018	-10000	0	0	177	177
RASA1	0.035	0.009	-10000	0	0	30	30
NCK1	0.035	0.008	-10000	0	0	27	27
PTPRJ	0.036	0.005	-10000	0	0	11	11
NCK/PLCgamma1	0.079	0.059	0.17	111	-10000	0	111
PDPK1	-0.004	0.054	-10000	0	-0.79	1	1
HGF/MET/SHIP	0.029	0.024	-10000	0	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.049	0.074	-10000	0	-0.13	40	40
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.035	0.008	-10000	0	0	28	28
STAT1 (dimer)/Cbp/p300	0.021	0.084	0.27	5	-0.22	19	24
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.042	0.063	-10000	0	-0.14	41	41
antigen processing and presentation of peptide antigen via MHC class I	-0.026	0.08	0.13	5	-0.19	59	64
CaM/Ca2+	0.046	0.08	-10000	0	-0.14	42	42
RAP1A	0.036	0.005	-10000	0	0	10	10
STAT1 (dimer)/SHP2	-0.023	0.06	0.16	17	-0.19	9	26
AKT1	-0.033	0.085	0.19	14	-0.23	32	46
MAP2K1	-0.028	0.056	0.14	21	-0.21	8	29
MAP3K11	-0.023	0.059	0.16	22	-0.18	7	29
IFNGR1	0.031	0.019	-10000	0	-0.037	19	19
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.03	0.13	-10000	0	-0.35	45	45
Rap1/GTP	-0.04	0.036	0.05	1	-0.15	10	11
CRKL/C3G	0.05	0.015	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.064	0.077	-10000	0	-0.13	35	35
CEBPB	-0.006	0.12	0.35	3	-0.43	22	25
STAT3	0.034	0.01	-10000	0	0	37	37
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.06	0.096	-10000	0	-0.74	4	4
STAT1	-0.026	0.06	0.17	18	-0.19	9	27
CALM1	0.033	0.012	-10000	0	0	57	57
IFN-gamma (dimer)	0.03	0.022	-10000	0	-0.037	39	39
PIK3CA	0.031	0.014	-10000	0	0	82	82
STAT1 (dimer)/PIAS1	-0.027	0.07	0.18	18	-0.21	17	35
CEBPB/PTGES2/Cbp/p300	0.01	0.09	-10000	0	-0.28	27	27
mol:Ca2+	0.046	0.072	-10000	0	-0.12	40	40
MAPK3	0.007	0.074	0.34	2	-0.52	2	4
STAT1 (dimer)	-0.027	0.11	0.19	7	-0.26	53	60
MAPK1	-0.04	0.2	0.34	2	-0.75	34	36
JAK2	0.027	0.022	-10000	0	-0.038	34	34
PIK3R1	0.032	0.012	-10000	0	0	63	63
JAK1	0.033	0.017	-10000	0	-0.036	18	18
CAMK2D	0	0	-10000	0	-10000	0	0
DAPK1	0.001	0.096	0.3	4	-0.4	12	16
SMAD7	-0.009	0.061	0.16	23	-0.14	21	44
CBL/CRKL/C3G	0.019	0.071	0.25	5	-0.18	6	11
PI3K	0.026	0.095	-10000	0	-0.16	71	71
IFNG	0.03	0.022	-10000	0	-0.037	39	39
apoptosis	0.014	0.086	0.31	3	-0.44	7	10
CAMK2G	0.024	0.018	-10000	0	0	180	180
STAT3 (dimer)	0.034	0.01	-10000	0	0	37	37
CAMK2A	0.036	0.005	-10000	0	0	8	8
CAMK2B	0.017	0.018	-10000	0	0	275	275
FRAP1	-0.039	0.077	0.17	14	-0.23	32	46
PRKCD	-0.033	0.081	0.21	12	-0.22	25	37
RAP1B	0	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.026	0.08	0.13	5	-0.19	59	64
PTPN2	0.036	0.007	-10000	0	0	17	17
EP300	0.034	0.011	-10000	0	0	50	50
IRF1	-0.036	0.059	0.21	3	-0.28	13	16
STAT1 (dimer)/PIASy	-0.026	0.065	0.19	14	-0.19	8	22
SOCS1	0.017	0.095	-10000	0	-1	4	4
mol:GDP	-0.023	0.066	0.17	22	-0.19	4	26
CASP1	-0.02	0.074	0.17	17	-0.16	65	82
PTGES2	0.035	0.007	-10000	0	0	20	20
IRF9	-0.002	0.044	0.12	16	-0.12	21	37
mol:PI-3-4-5-P3	0.013	0.084	-10000	0	-0.15	73	73
RAP1/GDP	-0.032	0.052	0.11	17	-0.17	7	24
CBL	-0.024	0.058	0.16	21	-0.18	6	27
MAP3K1	-0.023	0.056	0.15	18	-0.18	6	24
PIAS1	0.035	0.008	-10000	0	0	25	25
PIAS4	0.035	0.008	-10000	0	0	24	24
antigen processing and presentation of peptide antigen via MHC class II	-0.026	0.08	0.13	5	-0.19	59	64
PTPN11	-0.018	0.059	0.16	25	-0.18	6	31
CREBBP	0.037	0.005	-10000	0	0	9	9
RAPGEF1	0.035	0.007	-10000	0	0	18	18

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.047	0.011	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.035	0.007	-10000	0	0	20	20
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.036	0.004	-10000	0	0	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.035	0.007	-10000	0	0	21	21
RAC1-CDC42/GTP/PAK family	0.002	0.049	-10000	0	-0.14	43	43
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.034	0.01	-10000	0	0	39	39
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.036	0.005	-10000	0	0	8	8
FYN	0.03	0.014	-10000	0	0	88	88
MAP3K12	0.036	0.006	-10000	0	0	12	12
FGR	0.033	0.011	-10000	0	0	56	56
p38 alpha/TAB1	0.02	0.11	0.18	6	-0.26	38	44
PRKG1	0.026	0.017	-10000	0	0	147	147
DUSP8	0.034	0.01	-10000	0	0	40	40
PGK/cGMP/p38 alpha	0.004	0.096	0.17	1	-0.25	38	39
apoptosis	0.019	0.1	0.18	6	-0.25	38	44
RAL/GTP	0.027	0.037	-10000	0	-0.12	19	19
LYN	0.031	0.013	-10000	0	0	74	74
DUSP1	0.031	0.013	-10000	0	0	76	76
PAK1	0.036	0.006	-10000	0	0	16	16
SRC	0.034	0.009	-10000	0	0	34	34
RAC1/OSM/MEKK3/MKK3	0.046	0.037	-10000	0	-0.11	5	5
TRAF6	0.036	0.005	-10000	0	0	10	10
RAC1	0.025	0.017	-10000	0	0	163	163
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.031	0.028	-10000	0	-0.12	5	5
MAPK11	0.001	0.13	0.21	6	-0.32	39	45
BLK	0.036	0.007	-10000	0	0	17	17
HCK	0.027	0.016	-10000	0	0	141	141
MAP2K3	0.036	0.005	-10000	0	0	10	10
DUSP16	0	0	-10000	0	-10000	0	0
DUSP10	0.033	0.011	-10000	0	0	49	49
TRAF6/MEKK3	0.045	0.011	-10000	0	-0.1	1	1
MAP3K7IP1	0.034	0.009	-10000	0	0	36	36
MAPK14	0.012	0.11	0.18	9	-0.27	38	47
positive regulation of innate immune response	0.005	0.14	0.23	6	-0.34	43	49
LCK	0.035	0.007	-10000	0	0	18	18
p38alpha-beta/MKP7	0.002	0.13	0.22	6	-0.33	43	49
p38alpha-beta/MKP5	0.017	0.14	0.24	6	-0.34	36	42
PGK/cGMP	0.019	0.012	-10000	0	-10000	0	0
PAK2	0.035	0.007	-10000	0	0	21	21
p38alpha-beta/MKP1	0.008	0.14	0.24	6	-0.34	43	49
CDC42	0.035	0.008	-10000	0	0	26	26
RALB	0.036	0.006	-10000	0	0	16	16
RALA	0.024	0.018	-10000	0	0	182	182
PAK3	0.027	0.016	-10000	0	0	139	139

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.036	0.007	-10000	0	0	17	17
PTK2	0.034	0.009	-10000	0	0	34	34
CRKL	-0.018	0.044	0.097	27	-0.15	24	51
GRB2/SOS1/SHC	0.04	0.032	-10000	0	-0.12	14	14
HRAS	0.034	0.009	-10000	0	0	36	36
IRS1/Crk	0.019	0.048	-10000	0	-0.14	36	36
IGF-1R heterotetramer/IGF1/PTP1B	0.052	0.055	-10000	0	-0.15	28	28
AKT1	-0.034	0.075	0.15	28	-0.21	37	65
BAD	-0.039	0.073	0.14	27	-0.22	30	57
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.018	0.045	0.099	28	-0.16	24	52
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.026	0.049	0.22	1	-0.15	29	30
RAF1	-0.035	0.15	-10000	0	-0.55	29	29
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.047	0.054	-10000	0	-0.14	30	30
YWHAZ	0.035	0.007	-10000	0	0	21	21
IGF-1R heterotetramer/IGF1/IRS1	0.034	0.049	-10000	0	-0.16	24	24
PIK3CA	0.031	0.014	-10000	0	0	82	82
RPS6KB1	-0.032	0.072	0.16	31	-0.2	23	54
GNB2L1	0.037	0.002	-10000	0	0	2	2
positive regulation of MAPKKK cascade	-0.033	0.12	0.23	3	-0.43	29	32
PXN	0.036	0.004	-10000	0	0	7	7
PIK3R1	0.032	0.012	-10000	0	0	63	63
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
HRAS/GTP	0.016	0.054	-10000	0	-0.14	43	43
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.067	0.056	-10000	0	-0.12	34	34
IGF-1R heterotetramer	0.036	0.014	-10000	0	-0.034	1	1
IGF-1R heterotetramer/IGF1/IRS/Nck	0.049	0.06	-10000	0	-0.14	35	35
Crk/p130 Cas/Paxillin	0.038	0.055	0.22	1	-0.14	36	37
IGF1R	0.036	0.014	-10000	0	-0.034	1	1
IGF1	0.034	0.025	-10000	0	-0.059	29	29
IRS2/Crk	-0.03	0.058	0.1	19	-0.19	31	50
PI3K	0.04	0.088	-10000	0	-0.14	77	77
apoptosis	0.038	0.077	0.22	30	-0.16	22	52
HRAS/GDP	0.021	0.028	-10000	0	-0.13	16	16
PRKCD	0.005	0.064	0.18	9	-0.21	24	33
RAF1/14-3-3 E	-0.012	0.14	-10000	0	-0.48	29	29
BAD/14-3-3	-0.04	0.08	0.17	22	-0.23	30	52
PRKCZ	-0.027	0.07	0.16	32	-0.2	23	55
Crk/p130 Cas/Paxillin/FAK1	-0.046	0.074	0.13	27	-0.22	31	58
PTPN1	0.034	0.01	-10000	0	0	43	43
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.007	0.06	-10000	0	-0.22	25	25
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.038	0.071	-10000	0	-0.14	40	40
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	0.028	0.051	0.13	3	-0.14	35	38
GRB10	0.021	0.018	-10000	0	0	222	222
PTPN11	-0.018	0.045	0.099	28	-0.15	24	52
IRS1	0.01	0.041	0.12	3	-0.16	24	27
IRS2	-0.02	0.049	0.1	20	-0.2	24	44
IGF-1R heterotetramer/IGF1	0.04	0.051	-10000	0	-0.17	24	24
GRB2	0.035	0.007	-10000	0	0	18	18
PDPK1	-0.026	0.077	0.17	32	-0.21	23	55
YWHAE	0.035	0.008	-10000	0	0	27	27
PRKD1	-0.002	0.064	0.15	1	-0.24	28	29
SHC1	0.033	0.011	-10000	0	0	52	52

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.035	0.008	-10000	0	0	28	28
RAS family/GTP/Tiam1	-0.006	0.086	-10000	0	-0.2	63	63
NT3 (dimer)/TRKC	0.047	0.026	-10000	0	-0.14	6	6
NT3 (dimer)/TRKB	0.026	0.07	-10000	0	-0.13	74	74
SHC/Grb2/SOS1/GAB1/PI3K	-0.007	0.095	-10000	0	-0.21	74	74
RAPGEF1	0.035	0.007	-10000	0	0	18	18
BDNF	0.032	0.012	-10000	0	0	66	66
PIK3CA	0.031	0.014	-10000	0	0	82	82
DYNLT1	0.034	0.01	-10000	0	0	44	44
NTRK1	0.036	0.007	-10000	0	0	17	17
NTRK2	0.027	0.016	-10000	0	0	138	138
NTRK3	0.034	0.009	-10000	0	0	34	34
NT-4/5 (dimer)/TRKB	0.013	0.059	-10000	0	-0.12	78	78
neuron apoptosis	-0.008	0.12	0.32	39	-0.23	1	40
SHC 2-3/Grb2	0.007	0.13	0.24	1	-0.35	39	40
SHC1	0.033	0.011	-10000	0	0	52	52
SHC2	-0.01	0.12	-10000	0	-0.44	28	28
SHC3	-0.008	0.12	-10000	0	-0.41	29	29
STAT3 (dimer)	0.021	0.088	-10000	0	-0.29	37	37
NT3 (dimer)/TRKA	0.059	0.031	-10000	0	-10000	0	0
RIN/GDP	0.001	0.075	0.18	7	-0.22	25	32
GIPC1	0.035	0.008	-10000	0	0	24	24
KRAS	0.034	0.009	-10000	0	0	34	34
DNAJA3	-0.005	0.04	0.14	3	-0.18	2	5
RIN/GTP	0.011	0.036	-10000	0	-0.13	26	26
CCND1	-0.012	0.11	-10000	0	-0.5	26	26
MAGED1	0.035	0.008	-10000	0	0	26	26
PTPN11	0.036	0.005	-10000	0	0	11	11
RICS	0.033	0.011	-10000	0	0	47	47
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.04	0.032	-10000	0	-0.12	14	14
GRB2	0.035	0.007	-10000	0	0	18	18
NGF (dimer)/TRKA/MATK	0.045	0.014	-10000	0	-10000	0	0
TRKA/NEDD4-2	0.048	0.019	-10000	0	-0.14	1	1
ELMO1	0.018	0.018	-10000	0	0	259	259
RhoG/GTP/ELMO1/DOCK1	0.008	0.045	-10000	0	-0.12	45	45
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.034	0.009	-10000	0	0	36	36
DOCK1	0.024	0.018	-10000	0	0	183	183
GAB2	0.033	0.011	-10000	0	0	48	48
RIT2	0.025	0.017	-10000	0	0	168	168
RIT1	0.032	0.012	-10000	0	0	62	62
FRS2	0.035	0.009	-10000	0	0	30	30
DNM1	0.035	0.008	-10000	0	0	26	26
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.035	0.008	-10000	0	0	23	23
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.01	0.047	0.16	2	-0.17	10	12
mol:GDP	-0.002	0.1	0.21	8	-0.32	24	32
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.002	0.044	-10000	0	-0.13	44	44
RIT1/GDP	0.007	0.082	0.19	7	-0.24	22	29
TIAM1	0.033	0.011	-10000	0	0	46	46
PIK3R1	0.032	0.012	-10000	0	0	63	63
BDNF (dimer)/TRKB	0.027	0.071	-10000	0	-0.13	72	72
KIDINS220/CRKL/C3G	0.05	0.015	-10000	0	-10000	0	0
SHC/RasGAP	0.037	0.052	-10000	0	-0.16	31	31
FRS2 family/SHP2	0.067	0.028	-10000	0	-0.13	6	6
SHC/GRB2/SOS1/GAB1	0.049	0.046	-10000	0	-0.12	25	25
RIT1/GTP	0.014	0.041	-10000	0	-0.13	36	36
NT3 (dimer)	0.035	0.008	-10000	0	0	25	25
RAP1/GDP	-0.002	0.061	-10000	0	-0.18	25	25
KIDINS220/CRKL	0.035	0.008	-10000	0	0	28	28
BDNF (dimer)	0.032	0.012	-10000	0	0	66	66
ubiquitin-dependent protein catabolic process	0.043	0.017	-10000	0	-0.12	1	1
Schwann cell development	-0.011	0.016	-10000	0	-0.055	37	37
EHD4	0.034	0.01	-10000	0	0	38	38
FRS2 family/GRB2/SOS1	0.062	0.029	-10000	0	-0.11	8	8
FRS2 family/SHP2/CRK family/C3G/GAB2	0.008	0.071	-10000	0	-0.25	20	20
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.036	0.005	-10000	0	0	10	10
CDC42/GTP	0.018	0.083	-10000	0	-0.15	81	81
ABL1	0.032	0.013	-10000	0	0	69	69
SH2B family/GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
Rap1/GTP	0.003	0.069	-10000	0	-0.23	14	14
STAT3	0.021	0.088	-10000	0	-0.29	37	37
axon guidance	0.005	0.072	-10000	0	-0.14	81	81
MAPK3	-0.008	0.053	0.18	35	-10000	0	35
MAPK1	-0.009	0.049	0.18	29	-10000	0	29
CDC42/GDP	0.01	0.08	0.18	10	-0.22	23	33
NTF3	0.035	0.008	-10000	0	0	25	25
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.043	0.025	-10000	0	-0.12	9	9
PI3K	0.018	0.076	-10000	0	-0.16	72	72
FRS3	0.037	0.002	-10000	0	0	2	2
FAIM	0.035	0.009	-10000	0	0	29	29
GAB1	0.033	0.011	-10000	0	0	55	55
RASGRF1	-0.004	0.042	0.18	4	-0.14	1	5
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.018	0.021	0.09	11	-0.13	2	13
RGS19	0.033	0.011	-10000	0	0	52	52
CDC42	0.035	0.008	-10000	0	0	26	26
RAS family/GTP	0.009	0.1	0.23	1	-0.37	24	25
Rac1/GDP	0.01	0.069	0.18	8	-0.23	17	25
NGF (dimer)/TRKA/GRIT	0.039	0.035	-10000	0	-0.12	21	21
neuron projection morphogenesis	-0.035	0.24	-10000	0	-0.87	36	36
NGF (dimer)/TRKA/NEDD4-2	0.044	0.017	-10000	0	-0.12	1	1
MAP2K1	-0.011	0.06	0.18	19	-0.19	6	25
NGFR	0.032	0.013	-10000	0	0	71	71
NGF (dimer)/TRKA/GIPC/GAIP	0.014	0.042	-10000	0	-0.24	7	7
RAS family/GTP/PI3K	-0.023	0.11	-10000	0	-0.21	99	99
FRS2 family/SHP2/GRB2/SOS1	0.076	0.04	-10000	0	-0.14	10	10
NRAS	0.032	0.012	-10000	0	0	63	63
GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
PRKCI	0.035	0.008	-10000	0	0	27	27
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.025	0.017	-10000	0	0	163	163
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	0.011	0.087	-10000	0	-0.47	13	13
RASA1	0.035	0.009	-10000	0	0	30	30
TRKA/c-Abl	0.032	0.059	-10000	0	-0.14	48	48
SQSTM1	0.034	0.009	-10000	0	0	35	35
BDNF (dimer)/TRKB/GIPC	0.048	0.076	-10000	0	-0.12	67	67
NGF (dimer)/TRKA/p62/Atypical PKCs	0.053	0.035	-10000	0	-0.1	16	16
MATK	0.035	0.008	-10000	0	0	27	27
NEDD4L	0.034	0.01	-10000	0	0	45	45
RAS family/GDP	-0.02	0.057	-10000	0	-0.16	47	47
NGF (dimer)/TRKA	0.01	0.04	0.15	4	-0.13	4	8
Rac1/GTP	-0.014	0.055	-10000	0	-0.2	23	23
FRS2 family/SHP2/CRK family	0.087	0.057	-10000	0	-0.13	18	18

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.035	0.007	-10000	0	0	21	21
HDAC2	0.032	0.012	-10000	0	0	59	59
GNB1/GNG2	0.029	0.034	-10000	0	-0.12	14	14
forebrain development	0.034	0.061	0.25	4	-0.36	3	7
GNAO1	0.031	0.014	-10000	0	0	87	87
SMO/beta Arrestin2	0.034	0.031	-10000	0	-0.14	4	4
SMO	0.025	0.018	-10000	0	0	171	171
ARRB2	0.035	0.008	-10000	0	0	25	25
GLI3/SPOP	0.002	0.11	0.22	1	-0.3	38	39
mol:GTP	0	0.001	-10000	0	-10000	0	0
GSK3B	0.034	0.01	-10000	0	0	39	39
GNAI2	0.034	0.01	-10000	0	0	44	44
SIN3/HDAC complex	0.055	0.042	-10000	0	-0.13	17	17
GNAI1	0.018	0.018	-10000	0	0	262	262
XPO1	0.037	0.005	-10000	0	0	5	5
GLI1/Su(fu)	0.012	0.045	-10000	0	-0.26	6	6
SAP30	0.035	0.007	-10000	0	0	18	18
mol:GDP	0.025	0.018	-10000	0	0	171	171
MIM/GLI2A	0.041	0.014	0.12	11	-10000	0	11
IFT88	0.034	0.009	-10000	0	0	32	32
GNAI3	0.036	0.006	-10000	0	0	14	14
GLI2	0.001	0.088	-10000	0	-0.35	20	20
GLI3	-0.013	0.099	0.21	1	-0.3	34	35
CSNK1D	0.035	0.007	-10000	0	0	20	20
CSNK1E	0.032	0.013	-10000	0	0	68	68
SAP18	0.034	0.01	-10000	0	0	43	43
embryonic digit morphogenesis	0.034	0.009	-10000	0	0	32	32
GNG2	0	0	-10000	0	-10000	0	0
Gi family/GTP	-0.012	0.088	-10000	0	-0.26	38	38
SIN3B	0.034	0.009	-10000	0	0	33	33
SIN3A	0	0	-10000	0	-10000	0	0
GLI3/Su(fu)	-0.012	0.072	-10000	0	-0.26	26	26
GLI2/Su(fu)	-0.003	0.072	-10000	0	-0.31	18	18
FOXA2	0.049	0.037	-10000	0	-0.49	1	1
neural tube patterning	0.034	0.061	0.25	4	-0.36	3	7
SPOP	0.035	0.008	-10000	0	0	23	23
Su(fu)/PIAS1	0.046	0.038	0.098	147	-0.088	8	155
GNB1	0.035	0.007	-10000	0	0	20	20
CSNK1G2	0.035	0.008	-10000	0	0	27	27
CSNK1G3	0.036	0.005	-10000	0	0	11	11
MTSS1	0.041	0.014	0.12	11	-10000	0	11
embryonic limb morphogenesis	0.034	0.061	0.25	4	-0.36	3	7
SUFU	0.002	0.01	-10000	0	-0.11	4	4
LGALS3	0.028	0.015	-10000	0	0	117	117
catabolic process	0.012	0.14	0.29	2	-0.43	32	34
GLI3A/CBP	0.045	0.009	-10000	0	-10000	0	0
KIF3A	0.033	0.011	-10000	0	0	53	53
GLI1	0.034	0.062	0.25	4	-0.36	3	7
RAB23	0.035	0.009	-10000	0	0	31	31
CSNK1A1	0.036	0.006	-10000	0	0	12	12
IFT172	0	0	-10000	0	-10000	0	0
RBBP7	0.036	0.005	-10000	0	0	8	8
Su(fu)/Galectin3	0.037	0.04	0.098	119	-0.12	7	126
GNAZ	0.031	0.013	-10000	0	0	80	80
RBBP4	0.033	0.012	-10000	0	0	57	57
CSNK1G1	0.036	0.005	-10000	0	0	11	11
PIAS1	0.035	0.008	-10000	0	0	25	25
PRKACA	0.035	0.008	-10000	0	0	24	24
GLI2/SPOP	0.017	0.097	-10000	0	-0.32	25	25
STK36	0.001	0.003	0.022	4	-10000	0	4
Gi family/GNB1/GNG2/GDP	-0.017	0.1	-10000	0	-0.34	31	31
PTCH1	0.033	0.058	0.24	4	-0.33	3	7
MIM/GLI1	0.057	0.068	0.35	2	-0.33	3	5
CREBBP	0.045	0.009	-10000	0	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.001	0.093	0.17	1	-0.31	27	28

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.028	0.074	0.21	12	-0.27	10	22
FYN	-0.01	0.11	0.24	11	-0.3	34	45
LAT/GRAP2/SLP76	0.021	0.075	0.22	5	-0.29	12	17
IKBKB	0.036	0.003	-10000	0	0	4	4
AKT1	0.005	0.084	0.21	15	-0.24	23	38
B2M	0.037	0.009	-10000	0	0	24	24
IKBKG	-0.003	0.034	0.097	11	-0.1	8	19
MAP3K8	0.022	0.018	-10000	0	0	200	200
mol:Ca2+	-0.01	0.009	-10000	0	-0.04	3	3
integrin-mediated signaling pathway	0.024	0.007	-10000	0	-0.11	1	1
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.008	0.1	0.25	15	-0.3	21	36
TRPV6	0.39	0.59	1.2	163	-10000	0	163
CD28	0.037	0.001	-10000	0	-10000	0	0
SHC1	0.019	0.079	0.2	26	-0.32	10	36
receptor internalization	0.019	0.064	0.17	9	-0.3	9	18
PRF1	-0.14	0.31	-10000	0	-0.6	149	149
KRAS	0.034	0.009	-10000	0	0	34	34
GRB2	0.035	0.007	-10000	0	0	18	18
COT/AKT1	0.006	0.064	0.2	4	-0.21	18	22
LAT	0.012	0.075	0.21	13	-0.3	12	25
EntrezGene:6955	0.001	0.004	0.014	41	-10000	0	41
CD3D	0.035	0.011	-10000	0	0	45	45
CD3E	0.038	0.007	-10000	0	0	10	10
CD3G	0.037	0.008	-10000	0	0	18	18
RASGRP2	0.006	0.018	-10000	0	-0.15	4	4
RASGRP1	-0.021	0.13	0.22	25	-0.25	92	117
HLA-A	0.038	0.007	-10000	0	0	12	12
RASSF5	0	0	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.024	0.007	-10000	0	-0.11	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.011	0.054	0.13	35	-0.1	19	54
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.005	0.037	-10000	0	-0.12	28	28
PRKCA	0.001	0.06	0.17	22	-0.18	6	28
GRAP2	0.034	0.01	-10000	0	0	37	37
mol:IP3	0.003	0.055	-10000	0	-0.23	10	10
EntrezGene:6957	0.001	0.004	0.015	41	-10000	0	41
TCR/CD3/MHC I/CD8	0.019	0.05	0.15	12	-0.23	6	18
ORAI1	-0.34	0.5	-10000	0	-1.1	163	163
CSK	0.013	0.075	0.21	14	-0.3	12	26
B7 family/CD28	0.063	0.098	0.26	25	-0.28	11	36
CHUK	0.025	0.017	-10000	0	0	165	165
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.016	0.077	0.2	10	-0.33	12	22
PTPN6	0.008	0.08	0.23	13	-0.3	14	27
VAV1	0.018	0.077	0.21	25	-0.31	9	34
Monovalent TCR/CD3	0.022	0.017	0.11	7	-10000	0	7
CBL	0.036	0.005	-10000	0	0	8	8
LCK	0.006	0.093	0.24	14	-0.3	19	33
PAG1	0.015	0.074	0.21	11	-0.3	12	23
RAP1A	0.036	0.005	-10000	0	0	10	10
TCR/CD3/MHC I/CD8/LCK	0.015	0.078	0.21	10	-0.32	13	23
CD80	0.036	0.007	-10000	0	0	16	16
CD86	0.033	0.012	-10000	0	0	65	65
PDK1/CARD11/BCL10/MALT1	0.002	0.046	-10000	0	-0.14	27	27
HRAS	0.034	0.009	-10000	0	0	36	36
GO:0035030	0.012	0.075	0.2	23	-0.25	11	34
CD8A	0.001	0.004	0.015	41	-10000	0	41
CD8B	0.001	0.004	0.015	43	-10000	0	43
PTPRC	0.029	0.015	-10000	0	0	110	110
PDK1/PKC theta	0.007	0.092	0.24	22	-0.28	15	37
CSK/PAG1	0.011	0.072	0.21	13	-0.29	12	25
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	0.05	0.035	-10000	0	-0.15	13	13
GRAP2/SLP76	0.03	0.085	0.24	4	-0.3	15	19
STIM1	-0.071	0.11	1	1	-10000	0	1
RAS family/GTP	0.005	0.072	0.17	17	-0.18	29	46
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.019	0.066	0.18	9	-0.32	9	18
mol:DAG	-0.019	0.038	-10000	0	-0.21	10	10
RAP1A/GDP	0.009	0.028	0.073	24	-0.052	16	40
PLCG1	0.034	0.01	-10000	0	0	37	37
CD247	0.001	0.004	0.014	41	-10000	0	41
cytotoxic T cell degranulation	-0.13	0.3	-10000	0	-0.58	151	151
RAP1A/GTP	0.004	0.007	-10000	0	-0.054	4	4
mol:PI-3-4-5-P3	0.009	0.091	0.24	16	-0.26	21	37
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.012	0.069	0.18	1	-0.27	10	11
NRAS	0.032	0.012	-10000	0	0	63	63
ZAP70	0.037	0.002	-10000	0	0	2	2
GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
LAT/GRAP2/SLP76/VAV1	0.01	0.068	0.2	3	-0.29	8	11
MALT1	0.034	0.009	-10000	0	0	34	34
TRAF6	0.036	0.005	-10000	0	0	10	10
CD8 heterodimer	0.003	0.008	0.028	43	-10000	0	43
CARD11	0	0	-10000	0	-10000	0	0
PRKCB	-0.016	0.028	-10000	0	-0.15	10	10
PRKCE	0.001	0.06	0.17	23	-0.18	6	29
PRKCQ	0.009	0.096	0.25	21	-0.29	17	38
LCP2	0.031	0.013	-10000	0	0	75	75
BCL10	0.035	0.007	-10000	0	0	19	19
regulation of survival gene product expression	0.005	0.077	0.2	15	-0.22	18	33
IKK complex	0	0.039	0.13	13	-0.11	1	14
RAS family/GDP	-0.004	0.015	-10000	0	-0.041	38	38
MAP3K14	0.01	0.064	0.18	23	-0.17	18	41
PDPK1	0.005	0.08	0.21	18	-0.23	19	37
TCR/CD3/MHC I/CD8/Fyn	0.01	0.069	0.18	1	-0.29	13	14

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.026	0.017	-9999	0	144	144
ITGB7	0.036	0.006	-9999	0	14	14
ITGA4	0.036	0.006	-9999	0	13	13
alpha4/beta7 Integrin	0.052	0.012	-9999	-9999	0	0
alpha4/beta1 Integrin	0.038	0.025	-9999	-9999	0	0

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	0.003	0.1	-10000	0	-0.39	30	30
Crk/p130 Cas/Paxillin	-0.058	0.094	-10000	0	-0.19	142	142
JUN	-0.016	0.047	-10000	0	-0.26	10	10
HRAS	0.034	0.009	-10000	0	0	36	36
RET51/GFRalpha1/GDNF/GRB10	0.036	0.06	-10000	0	-0.12	28	28
RAP1A	0.036	0.005	-10000	0	0	10	10
FRS2	0.035	0.009	-10000	0	0	30	30
RAP1A/GDP	0.026	0.008	-10000	0	-0.13	1	1
RET51/GFRalpha1/GDNF/DOK1	0.062	0.046	-10000	0	-10000	0	0
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.036	0.005	-10000	0	0	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.035	0.008	-10000	0	0	23	23
RET9/GFRalpha1/GDNF/Enigma	0.047	0.033	-10000	0	-10000	0	0
RHOA	0.035	0.007	-10000	0	0	21	21
RAP1A/GTP	0.055	0.048	-10000	0	-0.11	1	1
GRB7	0.036	0.006	-10000	0	0	15	15
RET51/GFRalpha1/GDNF	0.061	0.047	-10000	0	-10000	0	0
MAPKKK cascade	-0.007	0.075	-10000	0	-0.18	15	15
BCAR1	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	0.038	0.046	-10000	0	-0.11	23	23
lamellipodium assembly	-0.027	0.083	0.13	1	-0.19	67	68
RET51/GFRalpha1/GDNF/SHC	0.058	0.051	-10000	0	-0.12	8	8
PIK3CA	0.031	0.014	-10000	0	0	82	82
RET9/GFRalpha1/GDNF/SHC	0.04	0.039	-10000	0	-0.11	8	8
RET9/GFRalpha1/GDNF/Shank3	0.032	0.022	-10000	0	-10000	0	0
MAPK3	-0.026	0.035	0.2	7	-10000	0	7
DOK1	0.037	0.002	-10000	0	0	2	2
DOK6	0	0	-10000	0	-10000	0	0
PXN	0.036	0.004	-10000	0	0	7	7
neurite development	-0.021	0.039	0.25	3	-0.21	8	11
DOK5	0.029	0.015	-10000	0	0	108	108
GFRA1	0.025	0.017	-10000	0	0	164	164
MAPK8	0	0.044	-10000	0	-0.17	20	20
HRAS/GTP	0.02	0.094	-10000	0	-0.12	119	119
tube development	0.025	0.028	0.2	3	-0.1	8	11
MAPK1	-0.025	0.035	0.22	5	-10000	0	5
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.013	0.064	-10000	0	-0.22	15	15
Rac1/GDP	0.017	0.02	-10000	0	-0.13	5	5
SRC	0.034	0.009	-10000	0	0	34	34
PDLIM7	0.036	0.005	-10000	0	0	9	9
RET51/GFRalpha1/GDNF/Dok6	0.057	0.043	-10000	0	-10000	0	0
SHC1	0.033	0.011	-10000	0	0	52	52
RET51/GFRalpha1/GDNF/Dok4	0.062	0.046	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok5	0.037	0.073	-10000	0	-0.12	67	67
PRKCA	0.036	0.004	-10000	0	0	6	6
HRAS/GDP	0.021	0.028	-10000	0	-0.13	16	16
CREB1	-0.034	0.098	-10000	0	-0.19	126	126
PIK3R1	0.032	0.012	-10000	0	0	63	63
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.012	0.066	-10000	0	-0.17	30	30
RET51/GFRalpha1/GDNF/Grb7	0.062	0.046	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.027	0.016	-10000	0	0	137	137
DOK4	0.036	0.006	-10000	0	0	13	13
JNK cascade	-0.017	0.048	-10000	0	-0.24	12	12
RET9/GFRalpha1/GDNF/FRS2	0.046	0.034	-10000	0	-10000	0	0
SHANK3	0	0	-10000	0	-10000	0	0
RASA1	0.035	0.009	-10000	0	0	30	30
NCK1	0.035	0.008	-10000	0	0	27	27
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.014	0.06	-10000	0	-0.18	18	18
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.027	0.094	-10000	0	-0.19	115	115
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.035	0.099	-10000	0	-0.19	133	133
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.009	0.048	-10000	0	-0.18	17	17
PI3K	-0.058	0.13	0.19	1	-0.25	125	126
SOS1	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.039	0.039	-10000	0	-0.1	8	8
GRB10	0.021	0.018	-10000	0	0	222	222
activation of MAPKK activity	0.011	0.051	-10000	0	-0.26	14	14
RET51/GFRalpha1/GDNF/FRS2	0.059	0.047	-10000	0	-10000	0	0
GAB1	0.033	0.011	-10000	0	0	55	55
IRS1	0.033	0.011	-10000	0	0	51	51
IRS2	0.03	0.014	-10000	0	0	94	94
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.01	0.055	-10000	0	-0.17	26	26
RET51/GFRalpha1/GDNF/PKC alpha	0.062	0.047	-10000	0	-10000	0	0
GRB2	0.035	0.007	-10000	0	0	18	18
PRKACA	0.035	0.008	-10000	0	0	24	24
GDNF	0.036	0.004	-10000	0	0	6	6
RAC1	0.025	0.017	-10000	0	0	163	163
RET51/GFRalpha1/GDNF/IRS1	0.055	0.057	-10000	0	-0.11	22	22
Rac1/GTP	-0.029	0.099	-10000	0	-0.23	63	63
RET9/GFRalpha1/GDNF	0.033	0.023	-10000	0	-10000	0	0
GFRalpha1/GDNF	0.037	0.026	-10000	0	-10000	0	0

×

Alternative NF-kappaB pathway

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
IKK alpha homodimer	0.036	0.028	-9999	-0.14	2	2
FBXW11	0.035	0.007	-9999	0	22	22
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.035	0.007	-9999	0	22	22
CHUK	0.025	0.017	-9999	0	165	165
NF kappa B2 p100/RelB	0.065	0.063	-9999	-0.11	13	13
NFKB1	0.035	0.007	-9999	0	18	18
MAP3K14	0.036	0.006	-9999	0	13	13
NF kappa B1 p50/RelB	0.048	0.024	-9999	-0.14	5	5
RELB	0.034	0.009	-9999	0	32	32
NFKB2	0.025	0.017	-9999	0	157	157
NF kappa B2 p52/RelB	0.033	0.023	-9999	-10000	0	0
regulation of B cell activation	0.033	0.023	-9999	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.052	0.038	-10000	0	-0.1	20	20
ER alpha/Gai/GDP/Gbeta gamma	-0.039	0.17	-10000	0	-0.54	38	38
AKT1	-0.05	0.23	-10000	0	-0.63	56	56
PIK3CA	0.031	0.014	-10000	0	0	82	82
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.045	0.23	-10000	0	-0.65	55	55
mol:Ca2+	0.006	0.052	0.17	18	-0.25	3	21
IGF1R	0.033	0.011	-10000	0	0	53	53
E2/ER alpha (dimer)/Striatin	0.046	0.012	-10000	0	-10000	0	0
SHC1	0.033	0.011	-10000	0	0	52	52
apoptosis	0.05	0.22	0.6	58	-10000	0	58
RhoA/GTP	-0.042	0.04	-10000	0	-0.14	50	50
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.012	0.15	-10000	0	-0.4	42	42
regulation of stress fiber formation	0.038	0.061	0.18	22	-0.18	8	30
E2/ERA-ERB (dimer)	0.045	0.015	-10000	0	-10000	0	0
KRAS	0.034	0.009	-10000	0	0	34	34
G13/GTP	0.043	0.014	-10000	0	-10000	0	0
pseudopodium formation	-0.038	0.061	0.18	8	-0.18	22	30
E2/ER alpha (dimer)/PELP1	0.044	0.023	-10000	0	-0.12	7	7
GRB2	0.035	0.007	-10000	0	0	18	18
GNG2	0	0	-10000	0	-10000	0	0
GNAO1	0.03	0.014	-10000	0	0	87	87
HRAS	0.034	0.009	-10000	0	0	36	36
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.012	0.16	-10000	0	-0.44	44	44
E2/ER beta (dimer)	0.026	0.006	-10000	0	-10000	0	0
mol:GDP	0.003	0.058	0.13	3	-0.19	26	29
mol:NADP	-0.012	0.16	-10000	0	-0.44	44	44
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	0.007	0.05	0.17	18	-0.34	1	19
IGF-1R heterotetramer	0.033	0.011	-10000	0	0	53	53
PLCB1	0.01	0.04	-10000	0	-0.34	1	1
PLCB2	0.009	0.04	-10000	0	-0.34	1	1
IGF1	0.035	0.007	-10000	0	0	21	21
mol:L-citrulline	-0.012	0.16	-10000	0	-0.44	44	44
RHOA	0.035	0.007	-10000	0	0	21	21
Gai/GDP	-0.067	0.24	-10000	0	-0.64	70	70
JNK cascade	0.025	0.006	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	0.035	0.009	-10000	0	0	31	31
GNAQ	0.035	0.009	-10000	0	0	30	30
ESR1	0.035	0.009	-10000	0	0	30	30
Gq family/GDP/Gbeta gamma	-0.002	0.15	-10000	0	-0.51	32	32
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.016	0.14	-10000	0	-0.69	17	17
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	0.004	0.16	0.25	8	-0.43	38	46
GNAZ	0.031	0.013	-10000	0	0	80	80
E2/ER alpha (dimer)	0.026	0.006	-10000	0	-10000	0	0
STRN	0.036	0.003	-10000	0	0	4	4
GNAL	0.036	0.006	-10000	0	0	13	13
PELP1	0.036	0.007	-10000	0	0	17	17
MAPK11	-0.016	0.006	-10000	0	-10000	0	0
GNAI2	0.034	0.01	-10000	0	0	44	44
GNAI3	0.036	0.006	-10000	0	0	14	14
GNAI1	0.018	0.018	-10000	0	0	262	262
HBEGF	-0.01	0.18	0.34	25	-0.49	38	63
cAMP biosynthetic process	0.037	0.016	-10000	0	-10000	0	0
SRC	-0.04	0.16	0.21	8	-0.5	40	48
PI3K	0.018	0.076	-10000	0	-0.16	72	72
GNB1	0.035	0.007	-10000	0	0	20	20
G13/GDP/Gbeta gamma	0.021	0.069	-10000	0	-0.17	34	34
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.026	0.12	-10000	0	-0.35	39	39
Gs family/GTP	0.047	0.02	-10000	0	-10000	0	0
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.041	0.065	-10000	0	-0.13	54	54
vasodilation	-0.01	0.16	0.22	1	-0.42	44	45
mol:DAG	0.007	0.05	0.17	18	-0.34	1	19
Gs family/GDP/Gbeta gamma	0.003	0.062	-10000	0	-0.18	30	30
MSN	-0.042	0.061	0.18	6	-0.2	22	28
Gq family/GTP	0.023	0.042	-10000	0	-0.35	1	1
mol:PI-3-4-5-P3	-0.043	0.22	-10000	0	-0.61	57	57
NRAS	0.032	0.012	-10000	0	0	63	63
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.01	0.16	0.42	44	-0.22	1	45
GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
RhoA/GDP	0.017	0.068	-10000	0	-0.19	29	29
NOS3	-0.014	0.17	-10000	0	-0.46	44	44
GNA11	0.033	0.011	-10000	0	0	51	51
MAPKKK cascade	0.003	0.15	-10000	0	-0.47	35	35
E2/ER alpha (dimer)/PELP1/Src	0.001	0.17	0.27	9	-0.44	39	48
ruffle organization	-0.038	0.061	0.18	8	-0.18	22	30
ROCK2	-0.033	0.064	0.2	7	-0.2	13	20
GNA14	0.035	0.009	-10000	0	0	29	29
GNA15	0.033	0.011	-10000	0	0	51	51
GNA13	0.035	0.007	-10000	0	0	20	20
MMP9	-0.023	0.17	0.36	9	-0.48	41	50
MMP2	-0.024	0.17	0.25	11	-0.49	41	52

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.051	0.39	0.77	2	-1	27	29
STAT6 (cleaved dimer)	-0.068	0.35	-10000	0	-0.89	37	37
IGHG1	-0.013	0.26	0.44	20	-0.8	22	42
IGHG3	-0.067	0.36	0.64	1	-0.87	39	40
AKT1	-0.024	0.27	0.52	5	-0.72	31	36
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	0.016	0.19	0.47	5	-0.55	7	12
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.008	0.26	0.5	5	-0.72	22	27
THY1	-0.13	0.5	0.8	2	-1.2	64	66
MYB	0.033	0.011	-10000	0	0	55	55
HMGA1	0.036	0.005	-10000	0	0	11	11
IL4/IL4R/JAK1/IL2R gamma/JAK3	0	0.26	0.54	9	-0.58	16	25
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.007	0.25	0.5	4	-0.77	17	21
SP1	0.029	0.076	0.12	95	-0.14	68	163
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.007	0.045	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.054	0.37	-10000	0	-0.93	31	31
SOCS1	-0.041	0.3	0.51	4	-0.66	33	37
SOCS3	-0.004	0.22	0.5	1	-0.64	3	4
FCER2	-0.028	0.32	0.66	1	-0.77	15	16
PARP14	0.001	0.001	-10000	0	-10000	0	0
CCL17	-0.064	0.38	0.73	1	-0.95	33	34
GRB2	0.035	0.007	-10000	0	0	18	18
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	0.003	0.22	0.45	10	-0.58	18	28
T cell proliferation	-0.071	0.38	0.67	1	-0.96	35	36
IL4R/JAK1	-0.072	0.38	0.67	1	-0.97	33	34
EGR2	-0.12	0.5	0.73	1	-1.2	58	59
JAK2	0.019	0.066	0.16	18	-10000	0	18
JAK3	0.034	0.016	-10000	0	-0.042	4	4
PIK3R1	0.032	0.012	-10000	0	0	63	63
JAK1	0.027	0.039	0.11	8	-10000	0	8
COL1A2	-0.11	0.48	0.54	2	-1.2	76	78
CCL26	-0.063	0.38	0.69	2	-0.9	39	41
IL4R	-0.059	0.41	0.81	3	-1.1	27	30
PTPN6	0.015	0.037	-10000	0	-0.057	11	11
IL13RA2	-0.32	0.66	0.77	3	-1.1	179	182
IL13RA1	0.024	0.067	0.16	18	-10000	0	18
IRF4	0.047	0.11	-10000	0	-10000	0	0
ARG1	0.005	0.21	0.52	3	-0.77	10	13
CBL	-0.008	0.24	0.49	6	-0.56	17	23
GTF3A	0.048	0.035	0.12	70	-0.15	3	73
PIK3CA	0.031	0.014	-10000	0	0	82	82
IL13RA1/JAK2	0.026	0.1	0.24	10	-0.16	23	33
IRF4/BCL6	0.042	0.11	-10000	0	-10000	0	0
CD40LG	0.041	0.004	0.14	1	-10000	0	1
MAPK14	-0.006	0.24	0.49	5	-0.56	15	20
mitosis	-0.019	0.26	0.51	5	-0.67	31	36
STAT6	-0.069	0.43	0.79	6	-1	39	45
SPI1	0.038	0.013	-10000	0	-10000	0	0
RPS6KB1	-0.023	0.25	0.48	6	-0.66	30	36
STAT6 (dimer)	-0.068	0.43	0.79	6	-1	39	45
STAT6 (dimer)/PARP14	-0.083	0.38	-10000	0	-0.95	39	39
mast cell activation	-0.002	0.016	-10000	0	-0.041	20	20
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	0.007	0.21	0.49	4	-0.56	6	10
FRAP1	-0.023	0.27	0.52	5	-0.71	31	36
LTA	-0.066	0.38	0.73	1	-0.99	27	28
FES	0.036	0.006	-10000	0	0	14	14
T-helper 1 cell differentiation	0.063	0.43	0.99	39	-0.79	6	45
CCL11	-0.068	0.36	-10000	0	-0.97	26	26
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	0.011	0.22	0.51	5	-0.59	4	9
IL2RG	0.034	0.016	-10000	0	-0.044	1	1
IL10	-0.051	0.39	0.72	3	-1	25	28
IRS1	0.033	0.011	-10000	0	0	51	51
IRS2	0.03	0.014	-10000	0	0	94	94
IL4	0.027	0.17	0.58	1	-0.84	5	6
IL5	-0.066	0.38	0.73	1	-1	27	28
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.059	0.39	0.67	12	-0.89	40	52
COL1A1	0.017	0.26	0.56	19	-0.81	15	34
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.076	0.38	-10000	0	-1.1	26	26
IL2R gamma/JAK3	0.054	0.019	-10000	0	-10000	0	0
TFF3	-0.06	0.38	0.73	1	-0.97	29	30
ALOX15	-0.066	0.38	0.73	1	-0.99	28	29
MYBL1	0.03	0.014	-10000	0	0	96	96
T-helper 2 cell differentiation	-0.046	0.34	0.64	4	-0.77	37	41
SHC1	0.033	0.011	-10000	0	0	52	52
CEBPB	0.034	0.016	0.11	1	-10000	0	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.016	0.26	0.52	5	-0.74	22	27
mol:PI-3-4-5-P3	-0.023	0.27	0.52	5	-0.71	31	36
PI3K	-0.028	0.28	0.52	5	-0.76	31	36
DOK2	0	0	-10000	0	-10000	0	0
ETS1	0.005	0.047	-10000	0	-0.087	11	11
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	0.004	0.22	0.44	11	-0.56	23	34
ITGB3	-0.066	0.38	0.73	1	-1	24	25
PIGR	-0.054	0.38	0.72	2	-1	25	27
IGHE	-0.003	0.079	0.18	39	-0.18	13	52
MAPKKK cascade	0.005	0.21	0.44	11	-0.55	23	34
BCL6	0.031	0.013	-10000	0	0	71	71
OPRM1	-0.065	0.38	0.73	1	-0.99	27	28
RETNLB	-0.063	0.38	0.69	2	-0.9	39	41
SELP	-0.062	0.38	0.8	2	-1	26	28
AICDA	-0.064	0.36	-10000	0	-0.96	25	25

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.008	0.071	-10000	0	-0.3	21	21
KLHL20	0.049	0.094	0.2	71	-0.19	18	89
CYFIP2	0.031	0.013	-10000	0	0	76	76
Rac1/GDP	0.009	0.062	0.2	1	-0.26	12	13
ENAH	0.007	0.074	-10000	0	-0.32	20	20
AP1M1	0	0	-10000	0	-10000	0	0
RAP1B	0	0	0	39	0	9	48
RAP1A	0.036	0.005	-10000	0	0	10	10
CTNNB1	0.036	0.006	-10000	0	0	15	15
CDC42/GTP	-0.023	0.056	0.12	24	-0.21	21	45
ABI1/Sra1/Nap1	-0.015	0.034	-10000	0	-0.13	29	29
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.083	0.039	-10000	0	-0.13	8	8
RAPGEF1	0	0.078	0.22	1	-0.29	16	17
CTNND1	0.035	0.009	-10000	0	0	31	31
regulation of calcium-dependent cell-cell adhesion	0.021	0.075	-10000	0	-0.3	22	22
CRK	0.007	0.08	-10000	0	-0.29	20	20
E-cadherin/gamma catenin/alpha catenin	0.062	0.035	-10000	0	-0.13	8	8
alphaE/beta7 Integrin	0.049	0.026	-10000	0	-0.14	7	7
IQGAP1	0.033	0.011	-10000	0	0	47	47
NCKAP1	0.037	0.002	-10000	0	0	2	2
Rap1/GTP/I-afadin	0.043	0.015	-10000	0	-0.1	1	1
DLG1	0.008	0.075	-10000	0	-0.3	22	22
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.034	0.044	-10000	0	-0.18	29	29
MLLT4	0.034	0.009	-10000	0	0	34	34
ARF6/GTP/NME1/Tiam1	0.036	0.033	-10000	0	-0.1	23	23
PI3K	-0.041	0.058	0.06	1	-0.23	29	30
ARF6	0.035	0.009	-10000	0	0	29	29
mol:Ca2+	0	0	0.001	68	0	29	97
E-cadherin/gamma catenin	0.048	0.018	-10000	0	-10000	0	0
TIAM1	0.033	0.011	-10000	0	0	46	46
E-cadherin(dimer)/Ca2+	0.071	0.054	-10000	0	-0.14	25	25
AKT1	-0.02	0.056	0.13	9	-0.18	24	33
PIK3R1	0.032	0.012	-10000	0	0	63	63
CDH1	0.034	0.01	-10000	0	0	37	37
RhoA/GDP	0.017	0.074	0.2	5	-0.25	15	20
actin cytoskeleton organization	0.041	0.076	0.17	72	-0.14	17	89
CDC42/GDP	0.016	0.072	0.2	4	-0.25	14	18
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.011	0.05	-10000	0	-0.2	23	23
ITGB7	0.036	0.006	-10000	0	0	14	14
RAC1	0.025	0.017	-10000	0	0	163	163
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.077	0.058	-10000	0	-0.15	25	25
E-cadherin/Ca2+/beta catenin/alpha catenin	0.056	0.031	-10000	0	-0.11	10	10
mol:GDP	0	0.076	0.2	4	-0.29	13	17
CDC42/GTP/IQGAP1	0.035	0.042	-10000	0	-0.12	33	33
JUP	0.033	0.011	-10000	0	0	51	51
p120 catenin/RhoA/GDP	0.031	0.082	0.22	5	-0.25	18	23
RAC1/GTP/IQGAP1	0.024	0.043	-10000	0	-0.12	30	30
PIP5K1C/AP1M1	0.02	0.03	-10000	0	-0.13	18	18
RHOA	0.035	0.007	-10000	0	0	21	21
CDC42	0.035	0.008	-10000	0	0	26	26
CTNNA1	0.036	0.007	-10000	0	0	18	18
positive regulation of S phase of mitotic cell cycle	0.015	0.048	0.12	18	-0.12	32	50
NME1	0	0	-10000	0	0	32	32
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	0.009	0.073	-10000	0	-0.3	20	20
regulation of cell-cell adhesion	-0.027	0.04	-10000	0	-0.17	25	25
WASF2	-0.008	0.018	-10000	0	-0.073	29	29
Rap1/GTP	-0.019	0.067	0.15	32	-0.22	22	54
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.091	0.051	-10000	0	-0.13	12	12
CCND1	0.017	0.057	0.14	18	-0.15	32	50
VAV2	0.024	0.11	-10000	0	-0.52	10	10
RAP1/GDP	-0.006	0.069	0.16	29	-0.25	15	44
adherens junction assembly	0.009	0.071	-10000	0	-0.3	20	20
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.025	0.017	-10000	0	0	158	158
PIP5K1C	0.033	0.011	-10000	0	0	47	47
regulation of heterotypic cell-cell adhesion	0.069	0.047	0.2	3	-0.14	13	16
E-cadherin/beta catenin	0.007	0.02	-10000	0	-0.099	5	5
mol:GTP	0	0	0.001	63	0	32	95
SRC	0.007	0.07	-10000	0	-0.29	21	21
PIK3CA	0.031	0.014	-10000	0	0	82	82
Rac1/GTP	-0.008	0.07	0.17	2	-0.29	18	20
E-cadherin/beta catenin/alpha catenin	0.064	0.036	-10000	0	-0.14	10	10
ITGAE	0.035	0.007	-10000	0	0	18	18
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.021	0.077	-10000	0	-0.3	22	22

×

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

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
MAP4K1	0.016	0.11	0.26	10	-0.38	21	31
CRKL	0.02	0.1	0.23	10	-0.39	22	32
HRAS	0.032	0.1	0.25	7	-0.32	22	29
mol:PIP3	0.058	0.12	0.3	27	-0.34	21	48
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0.036	0.004	-10000	0	0	7	7
GAB1	0.025	0.11	0.24	11	-0.4	22	33
FOXO3	0.055	0.16	0.31	34	-0.35	41	75
AKT1	0.056	0.17	0.33	32	-0.37	41	73
BAD	0.048	0.16	0.31	32	-0.36	42	74
megakaryocyte differentiation	0.025	0.1	0.24	11	-0.39	20	31
GSK3B	0.048	0.17	0.32	34	-0.37	43	77
RAF1	0.022	0.091	0.24	14	-0.27	23	37
SHC1	0.033	0.011	-10000	0	0	52	52
STAT3	0.018	0.1	0.23	5	-0.4	22	27
STAT1	0.015	0.2	-10000	0	-0.87	21	21
HRAS/SPRED1	0.024	0.089	0.22	8	-0.27	23	31
cell proliferation	0.009	0.094	0.23	4	-0.38	22	26
PIK3CA	0.031	0.014	-10000	0	0	82	82
TEC	0.036	0.004	-10000	0	0	6	6
RPS6KB1	0.056	0.12	0.27	20	-0.37	21	41
HRAS/SPRED2	0.043	0.099	0.25	10	-0.27	22	32
LYN/TEC/p62DOK	0.066	0.12	-10000	0	-0.4	22	22
MAPK3	0.02	0.087	0.26	20	-0.21	22	42
STAP1	0.025	0.1	0.23	5	-0.39	22	27
GRAP2	0.034	0.01	-10000	0	0	37	37
JAK2	0.015	0.17	-10000	0	-0.74	21	21
STAT1 (dimer)	0.02	0.2	-10000	0	-0.85	21	21
mol:Gleevec	-0.002	0.006	-10000	0	-0.023	1	1
GRB2/SOCS1/VAV1	0.073	0.12	0.28	1	-0.38	22	23
actin filament polymerization	0.027	0.1	0.23	5	-0.38	22	27
LYN	0.031	0.013	-10000	0	0	74	74
STAP1/STAT5A (dimer)	0.024	0.14	0.29	1	-0.54	21	22
PIK3R1	0.033	0.012	-10000	0	0	63	63
CBL/CRKL/GRB2	0.053	0.11	0.29	3	-0.38	21	24
PI3K	0.064	0.14	0.3	18	-0.38	21	39
PTEN	0.025	0.017	-10000	0	0	168	168
SCF/KIT/EPO/EPOR	0.023	0.22	-10000	0	-1	21	21
MAPK8	0.008	0.095	0.24	3	-0.39	22	25
STAT3 (dimer)	0.02	0.1	0.24	7	-0.39	22	29
positive regulation of transcription	0.02	0.078	0.23	22	-0.18	18	40
mol:GDP	0.042	0.098	0.24	1	-0.34	21	22
PIK3C2B	0.025	0.1	0.24	11	-0.39	22	33
CBL/CRKL	0.041	0.11	0.26	5	-0.38	21	26
FER	0.023	0.1	0.24	6	-0.39	22	28
SH2B3	0.025	0.1	0.23	5	-0.39	22	27
PDPK1	0.051	0.12	0.29	27	-0.32	21	48
SNAI2	0.026	0.11	0.23	11	-0.4	21	32
positive regulation of cell proliferation	0.028	0.17	-10000	0	-0.66	21	21
KITLG	0.039	0.021	-10000	0	-0.051	20	20
cell motility	0.028	0.17	-10000	0	-0.66	21	21
PTPN6	0.023	0.025	-10000	0	-0.033	68	68
EPOR	0.048	0.085	-10000	0	-10000	0	0
STAT5A (dimer)	0.032	0.14	0.3	2	-0.54	21	23
SOCS1	0.036	0.005	-10000	0	0	9	9
cell migration	-0.022	0.1	0.38	22	-0.24	6	28
SOS1	0	0	-10000	0	-10000	0	0
EPO	0.026	0.022	-10000	0	-0.036	14	14
VAV1	0.034	0.009	-10000	0	0	33	33
GRB10	0.011	0.088	0.3	4	-0.36	18	22
PTPN11	0.027	0.022	-10000	0	-0.027	67	67
SCF/KIT	0.029	0.11	0.25	5	-0.41	22	27
GO:0007205	-0.002	0.007	0.021	20	-0.021	3	23
MAP2K1	0.012	0.082	0.22	13	-0.22	26	39
CBL	0.036	0.005	-10000	0	0	8	8
KIT	0.005	0.24	-10000	0	-1.1	21	21
MAP2K2	0.017	0.091	0.3	19	-0.22	23	42
SHC/Grb2/SOS1	0.053	0.11	-10000	0	-0.36	21	21
STAT5A	0.033	0.14	0.3	2	-0.56	21	23
GRB2	0.035	0.007	-10000	0	0	18	18
response to radiation	0.027	0.11	0.23	12	-0.4	21	33
SHC/GRAP2	0.043	0.031	-10000	0	-0.14	8	8
PTPRO	0.024	0.1	0.24	11	-0.4	20	31
SH2B2	0.025	0.1	0.23	5	-0.39	22	27
DOK1	0.037	0.002	-10000	0	0	2	2
MATK	0.019	0.1	0.23	4	-0.39	22	26
CREBBP	0.052	0.045	0.14	4	-0.12	21	25
BCL2	0.039	0.14	-10000	0	-1	4	4

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.035	0.007	-10000	0	0	21	21
HDAC3	0.036	0.004	-10000	0	0	7	7
VDR	0.035	0.007	-10000	0	0	21	21
Cbp/p300/PCAF	0.042	0.024	-10000	0	-0.12	7	7
EP300	0.033	0.011	-10000	0	0	50	50
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.003	0.049	-10000	0	-0.22	7	7
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.036	0.004	-10000	0	0	5	5
AKT1	0.007	0.08	0.16	55	-0.23	11	66
RAR alpha/9cRA/Cyclin H	-0.027	0.13	-10000	0	-0.3	38	38
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.003	0.056	-10000	0	-0.2	21	21
CDC2	0.018	0.02	-10000	0	-0.001	249	249
response to UV	-0.001	0.007	-10000	0	-0.026	33	33
RAR alpha/Jnk1	0.022	0.028	0.16	1	-10000	0	1
NCOR2	0.037	0.002	-10000	0	0	2	2
VDR/VDR/Vit D3	0.026	0.005	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.028	0.15	-10000	0	-0.54	33	33
NCOA2	0.036	0.006	-10000	0	0	12	12
NCOA3	0.034	0.01	-10000	0	0	41	41
NCOA1	0.033	0.011	-10000	0	0	49	49
VDR/VDR/DNA	0.035	0.007	-10000	0	0	21	21
RARG	0.032	0.017	-10000	0	-0.023	44	44
RAR gamma1/9cRA	0.046	0.013	-10000	0	-10000	0	0
MAPK3	0.032	0.018	-10000	0	-0.031	37	37
MAPK1	0.034	0.01	-10000	0	0	44	44
MAPK8	0.024	0.022	-10000	0	-0.006	164	164
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.022	0.12	-10000	0	-0.36	33	33
RARA	0.006	0.037	-10000	0	-0.2	11	11
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.005	0.041	-10000	0	-0.17	10	10
PRKCA	0.031	0.027	0.076	4	-0.072	32	36
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.031	0.16	-10000	0	-0.62	33	33
RXRG	0.019	0.028	-10000	0	-10000	0	0
RXRA	-0.012	0.082	0.15	3	-0.3	24	27
RXRB	0.019	0.026	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.026	0.005	-10000	0	-10000	0	0
RBP1	0.026	0.016	-10000	0	0	142	142
CRBP1/9-cic-RA	-0.004	0.061	-10000	0	-0.13	90	90
RARB	0.032	0.021	-10000	0	-0.046	33	33
PRKCG	0.031	0.027	0.075	3	-0.071	33	36
MNAT1	0.034	0.01	-10000	0	0	38	38
RAR alpha/RXRs	-0.015	0.13	-10000	0	-0.41	25	25
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.006	0.09	-10000	0	-0.3	24	24
proteasomal ubiquitin-dependent protein catabolic process	-0.006	0.057	-10000	0	-0.19	13	13
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.03	0.16	-10000	0	-0.62	33	33
positive regulation of DNA binding	-0.032	0.12	-10000	0	-0.28	39	39
NRIP1	-0.054	0.27	-10000	0	-1.1	33	33
RXRs/RARs	-0.008	0.12	-10000	0	-0.41	33	33
RXRs/RXRs/DNA/9cRA	-0.035	0.11	-10000	0	-0.36	33	33
PRKACA	0.035	0.008	-10000	0	0	24	24
CDK7	0.035	0.008	-10000	0	0	24	24
TFIIH	0.059	0.051	-10000	0	-0.17	19	19
RAR alpha/9cRA	0.021	0.089	-10000	0	-0.18	23	23
CCNH	0.036	0.006	-10000	0	0	16	16
CREBBP	0.036	0.005	-10000	0	0	9	9
RAR gamma2/9cRA	0.056	0.051	-10000	0	-0.15	19	19

×

Caspase cascade in apoptosis

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
TOP1	-0.009	0.087	-10000	0	-0.28	28	28
ACTA1	-0.037	0.09	0.16	1	-0.29	33	34
NUMA1	-0.002	0.084	-10000	0	-0.34	14	14
SPTAN1	-0.045	0.091	0.2	5	-0.29	36	41
LIMK1	0.01	0.11	0.19	75	-0.35	13	88
BIRC3	0.031	0.014	-10000	0	0	82	82
BIRC2	0.036	0.006	-10000	0	0	12	12
BAX	0.034	0.01	-10000	0	0	43	43
CASP10	-0.008	0.032	0.083	47	-10000	0	47
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	-0.01	0.09	-10000	0	-0.3	25	25
DIABLO	0.036	0.004	-10000	0	0	6	6
apoptotic nuclear changes	-0.044	0.091	0.2	5	-0.29	36	41
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.036	0.005	-10000	0	0	11	11
GSN	-0.038	0.096	0.2	5	-0.3	33	38
MADD	0.036	0.006	-10000	0	0	15	15
TFAP2A	0.045	0.054	-10000	0	-0.44	5	5
BID	-0.001	0.041	0.11	5	-0.19	18	23
MAP3K1	-0.002	0.051	-10000	0	-0.39	5	5
TRADD	0.036	0.005	-10000	0	0	10	10
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.05	0.018	-10000	0	-0.14	2	2
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.042	0.098	0.2	12	-0.3	36	48
CASP9	0.034	0.009	-10000	0	0	34	34
DNA repair	0.034	0.071	0.22	33	-10000	0	33
neuron apoptosis	0.017	0.11	-10000	0	-0.61	15	15
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.025	0.088	-10000	0	-0.32	25	25
APAF1	0.036	0.003	-10000	0	0	3	3
CASP6	0.026	0.11	-10000	0	-0.84	6	6
TRAF2	0.036	0.006	-10000	0	0	16	16
ICAD/CAD	-0.047	0.084	0.21	1	-0.3	29	30
CASP7	-0.08	0.11	-10000	0	-0.23	144	144
KRT18	0.026	0.054	-10000	0	-0.45	5	5
apoptosis	-0.034	0.092	-10000	0	-0.34	20	20
DFFA	-0.043	0.086	0.17	1	-0.3	31	32
DFFB	-0.041	0.085	-10000	0	-0.31	29	29
PARP1	-0.034	0.071	-10000	0	-0.22	33	33
actin filament polymerization	-0.017	0.1	0.32	13	-0.18	75	88
TNF	0.036	0.003	-10000	0	0	4	4
CYCS	0.015	0.039	0.18	3	-0.24	3	6
SATB1	0.018	0.11	-10000	0	-0.73	6	6
SLK	-0.025	0.084	-10000	0	-0.29	31	31
p15 BID/BAX	0.001	0.061	0.15	2	-0.16	44	46
CASP2	0.06	0.1	0.22	128	-0.26	7	135
JNK cascade	0.002	0.051	0.38	5	-10000	0	5
CASP3	-0.04	0.09	-10000	0	-0.3	33	33
LMNB2	0.062	0.092	0.23	10	-0.37	4	14
RIPK1	0.035	0.007	-10000	0	0	20	20
CASP4	0.03	0.014	-10000	0	0	94	94
Mammalian IAPs/DIABLO	0.061	0.032	-10000	0	-0.16	6	6
negative regulation of DNA binding	0.045	0.054	-10000	0	-0.43	5	5
stress fiber formation	-0.036	0.084	-10000	0	-0.29	31	31
GZMB	-0.005	0.033	0.093	47	-10000	0	47
CASP1	-0.01	0.066	-10000	0	-0.2	54	54
LMNB1	0.043	0.13	0.24	11	-0.4	14	25
APP	0.017	0.11	-10000	0	-0.62	15	15
TNFRSF1A	0.032	0.012	-10000	0	0	65	65
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.011	0.002	0	13	-10000	0	13
VIM	-0.034	0.095	-10000	0	-0.35	21	21
LMNA	0.066	0.09	0.23	17	-0.39	3	20
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.018	0.058	0.16	1	-0.23	13	14
LRDD	0.035	0.007	-10000	0	0	21	21
SREBF1	-0.042	0.087	0.18	1	-0.31	30	31
APAF-1/Caspase 9	0.014	0.1	-10000	0	-0.61	12	12
nuclear fragmentation during apoptosis	-0.002	0.083	-10000	0	-0.34	14	14
CFL2	0.016	0.11	0.18	75	-0.33	13	88
GAS2	-0.033	0.091	0.2	2	-0.3	30	32
positive regulation of apoptosis	0.062	0.1	0.23	22	-0.38	7	29
PRF1	0.023	0.018	-10000	0	0	193	193

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.022	0.13	-10000	0	-0.63	18	18
epithelial cell differentiation	-0.006	0.14	-10000	0	-0.65	18	18
ITCH	0.029	0.031	0.11	1	-0.11	20	21
WWP1	-0.021	0.22	-10000	0	-1.1	18	18
FYN	0.03	0.014	-10000	0	0	88	88
EGFR	0.009	0.016	-10000	0	0	379	379
PRL	0.036	0.006	-10000	0	0	15	15
neuron projection morphogenesis	-0.026	0.11	0.25	6	-0.52	18	24
PTPRZ1	0.022	0.018	-10000	0	0	199	199
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.056	0.12	-10000	0	-0.54	18	18
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.005	0.11	-10000	0	-0.57	18	18
ADAM17	0.03	0.031	-10000	0	-0.1	22	22
ErbB4/ErbB4	0	0.14	-10000	0	-0.69	18	18
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.009	0.12	-10000	0	-0.62	18	18
NCOR1	0.035	0.008	-10000	0	0	27	27
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.017	0.12	-10000	0	-0.58	18	18
GRIN2B	-0.026	0.11	0.23	2	-0.55	18	20
ErbB4/ErbB2/betacellulin	0.026	0.12	-10000	0	-0.55	18	18
STAT1	0.034	0.01	-10000	0	0	40	40
HBEGF	0.035	0.007	-10000	0	0	21	21
PRLR	0.036	0.004	-10000	0	0	6	6
E4ICDs/ETO2	0.022	0.13	-10000	0	-0.63	18	18
axon guidance	-0.029	0.16	-10000	0	-0.79	18	18
NEDD4	0.029	0.031	0.11	1	-0.11	20	21
Prolactin receptor/Prolactin receptor/Prolactin	0.052	0.011	-10000	0	-10000	0	0
CBFA2T3	0.035	0.008	-10000	0	0	27	27
ErbB4/ErbB2/HBEGF	0.025	0.11	-10000	0	-0.55	18	18
MAPK3	-0.018	0.11	0.29	3	-0.52	18	21
STAT1 (dimer)	0.02	0.13	-10000	0	-0.63	18	18
MAPK1	-0.021	0.11	0.29	3	-0.53	18	21
JAK2	0.031	0.014	-10000	0	0	83	83
ErbB4/ErbB2/neuregulin 1 beta	0.005	0.11	-10000	0	-0.55	18	18
NRG1	-0.022	0.02	0.092	4	-0.084	18	22
NRG3	0	0	-10000	0	-10000	0	0
NRG2	0.036	0.004	-10000	0	0	7	7
NRG4	0	0	-10000	0	-10000	0	0
heart development	-0.029	0.16	-10000	0	-0.79	18	18
neural crest cell migration	0.005	0.11	-10000	0	-0.54	18	18
ERBB2	-0.022	0.022	0.1	7	-0.084	18	25
WWOX/E4ICDs	0.023	0.13	-10000	0	-0.63	18	18
SHC1	0.033	0.011	-10000	0	0	52	52
ErbB4/EGFR/neuregulin 4	-0.014	0.096	-10000	0	-0.46	18	18
apoptosis	-0.006	0.12	0.58	18	-10000	0	18
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.024	0.13	-10000	0	-0.63	18	18
ErbB4/ErbB2/epiregulin	0.025	0.12	-10000	0	-0.55	18	18
ErbB4/ErbB4/betacellulin/betacellulin	0.023	0.13	-10000	0	-0.63	18	18
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.064	0.13	-10000	0	-0.57	18	18
MDM2	-0.002	0.13	0.27	7	-0.6	18	25
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.019	0.1	-10000	0	-0.51	18	18
STAT5A	-0.035	0.15	-10000	0	-0.76	18	18
ErbB4/EGFR/neuregulin 1 beta	-0.003	0.087	-10000	0	-0.42	18	18
DLG4	0.036	0.006	-10000	0	0	12	12
GRB2/SHC	0.043	0.037	-10000	0	-0.15	14	14
E4ICDs/TAB2/NCoR1	0.031	0.13	-10000	0	-0.62	18	18
STAT5A (dimer)	0.002	0.16	-10000	0	-0.72	18	18
MAP3K7IP2	0.033	0.011	-10000	0	0	47	47
STAT5B (dimer)	-0.016	0.16	-10000	0	-0.76	18	18
LRIG1	0.031	0.014	-10000	0	0	85	85
EREG	0.035	0.008	-10000	0	0	23	23
BTC	0.036	0.005	-10000	0	0	10	10
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.03	0.16	-10000	0	-0.8	18	18
ERBB4	0	0.14	-10000	0	-0.69	18	18
STAT5B	0.036	0.004	-10000	0	0	5	5
YAP1	-0.07	0.2	-10000	0	-0.49	92	92
GRB2	0.035	0.007	-10000	0	0	18	18
ErbB4/ErbB2/neuregulin 4	0.002	0.11	-10000	0	-0.55	18	18
glial cell differentiation	-0.03	0.13	0.62	18	-10000	0	18
WWOX	0.036	0.006	-10000	0	0	15	15
cell proliferation	-0.011	0.11	-10000	0	-0.57	18	18

×

Aurora A signaling

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
Aurora A/GADD45A	0.023	0.058	0.16	1	-0.2	26	27
BIRC5	0.029	0.015	-10000	0	0	111	111
NFKBIA	-0.008	0.042	0.21	3	-0.18	16	19
CPEB1	0.033	0.011	-10000	0	0	55	55
AKT1	-0.006	0.033	0.17	2	-0.18	7	9
NDEL1	0.035	0.007	-10000	0	0	20	20
Aurora A/BRCA1	0.023	0.043	0.14	1	-0.15	23	24
NDEL1/TACC3	0.036	0.058	0.16	1	-0.14	37	38
GADD45A	0.031	0.013	-10000	0	0	77	77
GSK3B	0.035	0.015	0.089	25	0	39	64
PAK1/Aurora A	0.029	0.05	0.16	1	-0.16	24	25
MDM2	0.034	0.01	-10000	0	0	45	45
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.012	0.026	0.093	25	-10000	0	25
TP53	0.002	0.073	-10000	0	-0.24	35	35
DLG7	-0.004	0.042	0.1	41	-0.18	13	54
AURKAIP1	0	0	-10000	0	-10000	0	0
ARHGEF7	0.033	0.012	-10000	0	0	57	57
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.038	0.061	0.17	1	-0.16	37	38
G2/M transition of mitotic cell cycle	0.023	0.043	-10000	0	-0.15	23	23
AURKA	0.006	0.05	0.13	24	-0.21	19	43
AURKB	0.008	0.034	-10000	0	-0.14	26	26
CDC25B	-0.001	0.075	0.12	1	-0.28	28	29
G2/M transition checkpoint	0.001	0.036	0.088	1	-0.14	23	24
mRNA polyadenylation	0.015	0.051	-10000	0	-0.13	46	46
Aurora A/CPEB	0.016	0.052	0.14	1	-0.13	46	47
Aurora A/TACC1/TRAP/chTOG	0.051	0.082	-10000	0	-0.16	51	51
BRCA1	0.036	0.006	-10000	0	0	12	12
centrosome duplication	0.029	0.049	0.16	1	-0.16	24	25
regulation of centrosome cycle	0.035	0.057	0.15	1	-0.14	37	38
spindle assembly	0.049	0.081	-10000	0	-0.16	51	51
TDRD7	0.034	0.01	-10000	0	0	39	39
Aurora A/RasGAP/Survivin	0.039	0.074	-10000	0	-0.19	25	25
CENPA	0.002	0.063	-10000	0	-0.26	24	24
Aurora A/PP2A	0.029	0.05	0.16	1	-0.16	25	26
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	-0.007	0.052	0.13	1	-0.2	20	21
negative regulation of DNA binding	0.002	0.073	-10000	0	-0.24	36	36
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.041	0.046	-10000	0	-0.14	27	27
RASA1	0.035	0.009	-10000	0	0	30	30
Ajuba/Aurora A	0.001	0.036	0.089	1	-0.14	23	24
mitotic prometaphase	-0.004	0.01	0.068	10	-10000	0	10
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.05	0.13	24	-0.21	19	43
TACC1	0.035	0.008	-10000	0	0	23	23
TACC3	0.033	0.012	-10000	0	0	57	57
Aurora A/Antizyme1	0.023	0.044	0.14	1	-0.15	24	25
Aurora A/RasGAP	0.027	0.06	0.16	1	-0.22	23	24
OAZ1	0.035	0.009	-10000	0	0	30	30
RAN	0.036	0.005	-10000	0	0	10	10
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.036	0.015	0.088	27	0	24	51
GIT1	0.037	0.003	-10000	0	0	3	3
GIT1/beta-PIX/PAK1	0.058	0.047	-10000	0	-0.13	26	26
Importin alpha/Importin beta/TPX2	-0.012	0.026	0.093	25	-10000	0	25
PPP2R5D	0.036	0.004	-10000	0	0	5	5
Aurora A/TPX2	-0.028	0.056	0.096	4	-0.23	21	25
PAK1	0.036	0.006	-10000	0	0	16	16
CKAP5	0.034	0.01	-10000	0	0	37	37

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.033	0.011	-10000	0	0	50	50
HDAC4	0.035	0.009	-10000	0	0	30	30
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.003	0.04	-10000	0	-0.13	45	45
CDKN1A	-0.038	0.12	-10000	0	-0.46	37	37
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.034	0.01	-10000	0	0	43	43
FOXO3	0.001	0.033	0.25	7	-10000	0	7
FOXO1	0	0	-10000	0	-10000	0	0
FOXO4	0.006	0.023	-10000	0	-0.18	7	7
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.034	0.01	-10000	0	0	40	40
TAT	0.036	0.006	-10000	0	0	12	12
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.011	0.001	-10000	0	-10000	0	0
PPARGC1A	0.031	0.013	-10000	0	0	79	79
FHL2	0.028	0.016	-10000	0	0	126	126
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.038	0.046	0.16	30	-0.15	5	35
HIST2H4A	0.003	0.04	0.13	45	-10000	0	45
SIRT1/FOXO3a	0.027	0.041	0.15	40	-10000	0	40
SIRT1	0.033	0.047	0.18	40	-10000	0	40
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.047	0.056	0.17	26	-0.13	16	42
SIRT1/Histone H1b	0.028	0.045	0.18	2	-0.16	5	7
apoptosis	-0.048	0.052	0.12	10	-0.17	28	38
SIRT1/PGC1A	0.03	0.044	0.15	28	-0.12	13	41
p53/SIRT1	0.042	0.091	0.33	36	-0.15	20	56
SIRT1/FOXO4	0.025	0.043	0.15	30	-0.14	11	41
FOXO1/FHL2/SIRT1	0.022	0.042	0.14	22	-0.1	21	43
HIST1H1E	0.013	0.023	-10000	0	-0.18	6	6
SIRT1/p300	0.036	0.05	0.16	32	-0.14	11	43
muscle cell differentiation	0.004	0.037	0.12	4	-0.12	33	37
TP53	0.04	0.046	0.18	42	-10000	0	42
KU70/SIRT1/BAX	0.048	0.053	0.17	28	-0.12	10	38
CREBBP	0.036	0.005	-10000	0	0	9	9
MEF2D	0.036	0.006	-10000	0	0	12	12
HIV-1 Tat/SIRT1	0.039	0.045	0.16	31	-0.15	4	35
ACSS2	0.003	0.04	0.13	45	-10000	0	45
SIRT1/PCAF/MYOD	-0.004	0.037	0.12	33	-0.12	4	37

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	-0.011	0.027	0.086	36	-10000	0	36
SNTA1	0.032	0.013	-10000	0	0	71	71
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.017	0.037	0.083	52	-0.13	12	64
MAPK12	-0.01	0.031	0.2	4	-0.17	9	13
CCND1	-0.019	0.1	-10000	0	-0.37	40	40
p38 gamma/SNTA1	-0.01	0.038	0.2	4	-0.16	10	14
MAP2K3	0.036	0.005	-10000	0	0	10	10
PKN1	0.033	0.011	-10000	0	0	48	48
G2/M transition checkpoint	-0.01	0.03	0.2	4	-0.17	9	13
MAP2K6	-0.005	0.036	0.22	6	-0.18	10	16
MAPT	-0.025	0.077	0.16	5	-0.2	74	79
MAPK13	-0.014	0.03	0.093	36	-10000	0	36
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.01	0.032	-10000	0	-0.2	11	11

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.036	0.005	-10000	0	0	11	11
Caspase 8 (4 units)	-0.011	0.097	-10000	0	-0.24	24	24
NEF	0.002	0	-10000	0	-10000	0	0
NFKBIA	0.038	0.019	0.078	64	-10000	0	64
BIRC3	-0.025	0.029	0.18	2	-0.2	2	4
CYCS	-0.004	0.078	0.18	46	-0.24	9	55
RIPK1	0.035	0.007	-10000	0	0	20	20
CD247	0.002	0	-10000	0	-10000	0	0
MAP2K7	-0.01	0.1	-10000	0	-0.4	6	6
protein ubiquitination	0.012	0.065	0.21	3	-0.25	7	10
CRADD	0.036	0.005	-10000	0	0	11	11
DAXX	0.036	0.004	-10000	0	0	6	6
FAS	0.019	0.018	-10000	0	0	241	241
BID	-0.003	0.057	-10000	0	-0.28	9	9
NF-kappa-B/RelA/I kappa B alpha	0.076	0.055	-10000	0	-0.14	17	17
TRADD	0.036	0.005	-10000	0	0	10	10
MAP3K5	0.03	0.014	-10000	0	0	90	90
CFLAR	0.036	0.005	-10000	0	0	8	8
FADD	0.036	0.006	-10000	0	0	12	12
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.076	0.055	-10000	0	-0.14	17	17
MAPK8	-0.006	0.094	-10000	0	-0.37	7	7
APAF1	0.037	0.003	-10000	0	0	3	3
TRAF1	0.035	0.008	-10000	0	0	24	24
TRAF2	0.036	0.006	-10000	0	0	16	16
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.002	0.061	-10000	0	-0.28	9	9
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.029	0.077	-10000	0	-0.28	11	11
CHUK	0.012	0.067	0.21	3	-0.27	7	10
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.039	0.084	-10000	0	-0.12	61	61
TCRz/NEF	0.007	0.001	-10000	0	-10000	0	0
TNF	0.036	0.003	-10000	0	0	4	4
FASLG	0.018	0.003	-10000	0	-10000	0	0
NFKB1	0.042	0.016	0.078	72	-10000	0	72
TNFR1A/BAG4/TNF-alpha	0.053	0.056	-10000	0	-0.13	41	41
CASP6	0.005	0.11	-10000	0	-0.56	7	7
CASP7	-0.034	0.14	0.28	10	-0.33	26	36
RELA	0.043	0.015	0.079	74	-10000	0	74
CASP2	0.025	0.017	-10000	0	0	165	165
CASP3	-0.001	0.11	0.27	9	-0.35	12	21
TNFRSF1A	0.032	0.012	-10000	0	0	65	65
TNFR1A/BAG4	0.035	0.055	-10000	0	-0.14	42	42
CASP8	0.036	0.006	-10000	0	0	13	13
CASP9	0.034	0.009	-10000	0	0	34	34
MAP3K14	0.024	0.077	0.19	2	-0.29	8	10
APAF-1/Caspase 9	-0.011	0.084	0.17	9	-0.27	6	15
BCL2	-0.016	0.091	0.27	1	-0.34	6	7

×

Insulin Pathway

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
CBL/APS/CAP	0.031	0.049	-10000	0	-0.11	21	21
TC10/GTP	0.026	0.048	-10000	0	-0.12	21	21
Insulin Receptor/Insulin/IRS1/Shp2	0.076	0.059	-10000	0	-0.13	27	27
HRAS	0.034	0.009	-10000	0	0	36	36
APS homodimer	0	0	-10000	0	-10000	0	0
GRB14	0.032	0.013	-10000	0	0	70	70
FOXO3	-0.009	0.016	0.019	8	-0.041	67	75
AKT1	-0.025	0.088	0.22	17	-0.21	25	42
INSR	0.033	0.022	-10000	0	-0.039	34	34
Insulin Receptor/Insulin	0.055	0.063	0.22	3	-0.14	34	37
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.021	0.018	-10000	0	0	222	222
SORBS1	0.025	0.017	-10000	0	0	158	158
CRK	0.035	0.008	-10000	0	0	23	23
PTPN1	-0.023	0.048	0.15	16	-0.26	8	24
CAV1	-0.011	0.037	0.17	6	-0.19	8	14
CBL/APS/CAP/Crk-II/C3G	0.049	0.054	-10000	0	-0.11	14	14
Insulin Receptor/Insulin/IRS1/NCK2	0.074	0.064	-10000	0	-0.14	30	30
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.035	0.079	-10000	0	-0.13	76	76
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.025	0.074	-10000	0	-0.32	12	12
RPS6KB1	-0.031	0.081	0.2	19	-0.21	25	44
PARD6A	0.035	0.007	-10000	0	0	19	19
CBL	0.036	0.005	-10000	0	0	8	8
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.021	0.019	-10000	0	-10000	0	0
PIK3R1	0.032	0.012	-10000	0	0	63	63
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.033	0.086	0.17	22	-0.22	27	49
HRAS/GTP	-0.034	0.035	-10000	0	-0.13	41	41
Insulin Receptor	0.033	0.022	-10000	0	-0.039	34	34
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.084	0.069	-10000	0	-0.13	32	32
PRKCI	0.025	0.088	-10000	0	-0.41	17	17
Insulin Receptor/Insulin/GRB14/PDK1	0.015	0.068	-10000	0	-0.14	71	71
SHC1	0.033	0.011	-10000	0	0	52	52
negative regulation of MAPKKK cascade	0.029	0.056	-10000	0	-10000	0	0
PI3K	0.047	0.087	-10000	0	-0.14	76	76
NCK2	0.036	0.007	-10000	0	0	17	17
RHOQ	0.036	0.006	-10000	0	0	16	16
mol:H2O2	-0.004	0.006	0.031	1	-0.034	8	9
HRAS/GDP	0.021	0.028	-10000	0	-0.13	16	16
AKT2	-0.026	0.079	0.21	16	-0.2	14	30
PRKCZ	0.003	0.077	-10000	0	-0.39	17	17
SH2B2	0	0	-10000	0	-10000	0	0
SHC/SHIP	-0.014	0.05	0.16	20	-0.15	4	24
F2RL2	0.036	0.004	-10000	0	0	6	6
TRIP10	0.034	0.009	-10000	0	0	35	35
Insulin Receptor/Insulin/Shc	0.058	0.038	-10000	0	-0.13	8	8
TC10/GTP/CIP4/Exocyst	0.042	0.03	-10000	0	-0.12	14	14
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.074	0.048	-10000	0	-0.13	14	14
RAPGEF1	0.035	0.007	-10000	0	0	18	18
RASA1	0.035	0.009	-10000	0	0	30	30
NCK1	0.035	0.008	-10000	0	0	27	27
CBL/APS/CAP/Crk-II	0.044	0.041	-10000	0	-0.11	14	14
TC10/GDP	0.023	0.025	-10000	0	-0.13	12	12
Insulin Receptor/Insulin/SHC/GRB10	0.044	0.066	-10000	0	-0.14	30	30
INPP5D	-0.018	0.03	0.064	24	-0.11	21	45
SOS1	0	0	-10000	0	-10000	0	0
SGK1	-0.006	0.005	-10000	0	-10000	0	0
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.036	0.005	-10000	0	0	11	11
IRS1	0.033	0.011	-10000	0	0	51	51
p62DOK/RasGAP	0.03	0.057	-10000	0	-10000	0	0
INS	0.035	0.024	0.082	30	-0.039	33	63
mol:PI-3-4-P2	-0.018	0.029	0.064	24	-0.11	21	45
GRB2	0.035	0.007	-10000	0	0	18	18
EIF4EBP1	-0.034	0.079	0.2	14	-0.22	24	38
PTPRA	0.032	0.017	-10000	0	-0.052	7	7
PIK3CA	0.031	0.014	-10000	0	0	82	82
TC10/GTP/CIP4	0.042	0.03	-10000	0	-0.12	14	14
PDPK1	0.036	0.005	-10000	0	0	8	8
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.015	0.054	0.14	1	-0.16	32	33
Insulin Receptor/Insulin/IRS1	0.056	0.047	-10000	0	-0.12	21	21
Insulin Receptor/Insulin/IRS3	0.048	0.033	-10000	0	-0.07	7	7
Par3/Par6	0.074	0.041	-10000	0	-0.11	16	16

×

Regulation of cytoplasmic and nuclear SMAD2/3 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
SMAD4	0.032	0.012	-10000	0	0	59	59
SMAD2	-0.018	0.066	0.16	3	-0.22	31	34
SMAD3	0.004	0.06	-10000	0	-0.34	8	8
SMAD3/SMAD4	-0.009	0.17	-10000	0	-0.5	44	44
SMAD4/Ubc9/PIASy	0.054	0.054	-10000	0	-0.13	35	35
SMAD2/SMAD2/SMAD4	0.025	0.1	-10000	0	-0.25	29	29
PPM1A	0.035	0.009	-10000	0	0	31	31
CALM1	0.033	0.012	-10000	0	0	57	57
SMAD2/SMAD4	-0.001	0.069	-10000	0	-0.21	31	31
MAP3K1	0.035	0.007	-10000	0	0	20	20
TRAP-1/SMAD4	0.036	0.054	-10000	0	-0.14	40	40
MAPK3	0.036	0.003	-10000	0	0	4	4
MAPK1	0.034	0.01	-10000	0	0	44	44
NUP214	0.035	0.007	-10000	0	0	18	18
CTDSP1	0.036	0.006	-10000	0	0	15	15
CTDSP2	0.033	0.012	-10000	0	0	58	58
CTDSPL	0.036	0.006	-10000	0	0	13	13
KPNB1	0.035	0.008	-10000	0	0	23	23
TGFBRAP1	0.036	0.005	-10000	0	0	10	10
UBE2I	0.036	0.004	-10000	0	0	6	6
NUP153	0.035	0.009	-10000	0	0	30	30
KPNA2	0.034	0.01	-10000	0	0	40	40
PIAS4	0.035	0.008	-10000	0	0	24	24

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.05	0.024	-10000	0	-0.14	6	6
Necdin/E2F1	-0.017	0.085	-10000	0	-0.14	148	148
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.073	0.048	-10000	0	-0.12	23	23
NGF (dimer)/p75(NTR)/BEX1	0.01	0.064	-10000	0	-0.12	95	95
NT-4/5 (dimer)/p75(NTR)	0.023	0.009	-10000	0	-10000	0	0
IKBKB	0.036	0.003	-10000	0	0	4	4
AKT1	-0.016	0.078	0.2	25	-0.2	23	48
IKBKG	0.037	0	-10000	0	-10000	0	0
BDNF	0.032	0.012	-10000	0	0	66	66
MGDIs/NGR/p75(NTR)/LINGO1	0.021	0.009	-10000	0	-10000	0	0
FURIN	0.036	0.005	-10000	0	0	9	9
proBDNF (dimer)/p75(NTR)/Sortilin	0.055	0.034	-10000	0	-0.13	2	2
LINGO1	0	0	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	0.022	0.069	-10000	0	-0.16	50	50
proBDNF (dimer)	0.032	0.012	-10000	0	0	66	66
NTRK1	0.036	0.007	-10000	0	0	17	17
RTN4R	0	0	-10000	0	-10000	0	0
neuron apoptosis	0.005	0.11	0.28	1	-0.37	28	29
IRAK1	0.035	0.007	-10000	0	0	19	19
SHC1	-0.003	0.036	0.092	61	-10000	0	61
ARHGDIA	0.035	0.007	-10000	0	0	18	18
RhoA/GTP	0.024	0.019	-10000	0	-0.13	7	7
Gamma Secretase	0.08	0.072	-10000	0	-0.16	28	28
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.039	0.059	-10000	0	-0.11	54	54
MAGEH1	0.032	0.013	-10000	0	0	70	70
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.004	0.076	-10000	0	-0.11	147	147
Mammalian IAPs/DIABLO	0.057	0.035	-10000	0	-0.16	6	6
proNGF (dimer)	0	0	-10000	0	-10000	0	0
MAGED1	0.035	0.008	-10000	0	0	26	26
APP	0.035	0.007	-10000	0	0	20	20
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
ZNF274	0.034	0.009	-10000	0	0	36	36
RhoA/GDP/RHOGDI	0.05	0.03	0.18	1	-0.1	6	7
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	0.003	0.054	0.22	7	-10000	0	7
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.017	0.056	-10000	0	-0.18	32	32
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.042	0.019	-10000	0	-0.12	1	1
NCSTN	0.035	0.009	-10000	0	0	29	29
mol:GTP	0.031	0.041	-10000	0	-0.12	29	29
PSENEN	0.035	0.009	-10000	0	0	31	31
mol:ceramide	-0.007	0.044	0.19	7	-10000	0	7
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.013	0.054	-10000	0	-0.27	10	10
p75(NTR)/beta APP	0.043	0.032	-10000	0	-0.14	9	9
BEX1	0.028	0.015	-10000	0	0	115	115
mol:GDP	-0.008	0.003	-10000	0	-10000	0	0
NGF (dimer)	0.046	0.034	-10000	0	-10000	0	0
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.04	0.017	-10000	0	-10000	0	0
PIK3R1	0.032	0.012	-10000	0	0	63	63
RAC1/GTP	0.024	0.024	-10000	0	-0.097	5	5
MYD88	0.034	0.009	-10000	0	0	36	36
CHUK	0.025	0.017	-10000	0	0	165	165
NGF (dimer)/p75(NTR)/PKA	0.032	0.041	-10000	0	-0.12	29	29
RHOB	0.031	0.013	-10000	0	0	74	74
RHOA	0.035	0.007	-10000	0	0	21	21
MAGE-G1/E2F1	0.025	0.007	-10000	0	-10000	0	0
NT3 (dimer)	0.035	0.008	-10000	0	0	25	25
TP53	-0.015	0.063	0.22	7	-0.21	6	13
PRDM4	-0.007	0.045	0.19	7	-10000	0	7
BDNF (dimer)	0.08	0.035	-10000	0	-10000	0	0
PIK3CA	0.031	0.014	-10000	0	0	82	82
SORT1	0.036	0.006	-10000	0	0	14	14
activation of caspase activity	0.066	0.046	-10000	0	-0.12	23	23
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.057	0.031	-10000	0	-0.11	5	5
RHOC	0.035	0.007	-10000	0	0	19	19
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	0.013	0.1	0.2	31	-0.31	16	47
DIABLO	0.036	0.004	-10000	0	0	6	6
SMPD2	-0.007	0.044	0.19	7	-10000	0	7
APH1B	0.036	0.006	-10000	0	0	14	14
APH1A	0.036	0.006	-10000	0	0	12	12
proNGF (dimer)/p75(NTR)/Sortilin	0.041	0.023	-10000	0	-0.12	4	4
PSEN1	0.033	0.011	-10000	0	0	47	47
APAF-1/Pro-Caspase 9	0.05	0.018	-10000	0	-0.14	2	2
NT3 (dimer)/p75(NTR)	0.044	0.021	-10000	0	-10000	0	0
MAPK8	0	0.076	0.2	17	-0.27	8	25
MAPK9	0.025	0.086	0.2	36	-0.26	8	44
APAF1	0.037	0.003	-10000	0	0	3	3
NTF3	0.035	0.008	-10000	0	0	25	25
NTF4	0	0	-10000	0	-10000	0	0
NDN	0.018	0.018	-10000	0	0	259	259
RAC1/GDP	0.017	0.02	-10000	0	-0.13	5	5
RhoA-B-C/GDP	0.049	0.074	-10000	0	-0.15	54	54
p75 CTF/Sortilin/TRAF6/NRIF	0.076	0.056	-10000	0	-0.12	32	32
RhoA-B-C/GTP	0.031	0.041	-10000	0	-0.12	29	29
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.088	0.059	-10000	0	-0.12	25	25
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.086	0.029	-10000	0	-0.12	2	2
PRKACB	0.033	0.011	-10000	0	0	48	48
proBDNF (dimer)/p75 ECD	0.046	0.019	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.031	0.014	-10000	0	0	82	82
BIRC2	0.036	0.006	-10000	0	0	12	12
neuron projection morphogenesis	-0.016	0.071	0.14	26	-0.16	29	55
BAD	0.008	0.089	0.2	20	-0.28	14	34
RIPK2	0.036	0.006	-10000	0	0	14	14
NGFR	0.032	0.013	-10000	0	0	71	71
CYCS	-0.012	0.041	0.2	4	-0.19	3	7
ADAM17	0.036	0.006	-10000	0	0	13	13
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.057	0.03	-10000	0	-0.11	3	3
BCL2L11	0.008	0.089	0.2	20	-0.28	13	33
BDNF (dimer)/p75(NTR)	0.041	0.023	-10000	0	-10000	0	0
PI3K	0.028	0.068	-10000	0	-0.12	70	70
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.039	0.021	-10000	0	-0.1	4	4
NDNL2	0	0	-10000	0	-10000	0	0
YWHAE	0.035	0.008	-10000	0	0	27	27
PRKCI	0.035	0.008	-10000	0	0	27	27
NGF (dimer)/p75(NTR)	0.023	0.009	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.05	0.048	-10000	0	-0.12	27	27
TRAF6	0.036	0.005	-10000	0	0	10	10
RAC1	0.025	0.017	-10000	0	0	163	163
PRKCZ	0	0	-10000	0	-10000	0	0
PLG	0.034	0.009	-10000	0	0	35	35
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	0.032	0.035	0.14	16	-0.15	2	18
SQSTM1	0.034	0.009	-10000	0	0	35	35
NGFRAP1	0.036	0.006	-10000	0	0	13	13
CASP3	0.008	0.088	0.19	21	-0.27	15	36
E2F1	0.034	0.009	-10000	0	0	36	36
CASP9	0.034	0.009	-10000	0	0	34	34
IKK complex	0.038	0.068	-10000	0	-0.24	10	10
NGF (dimer)/TRKA	0.026	0.005	-10000	0	-10000	0	0
MMP7	0.027	0.016	-10000	0	0	138	138
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.071	0.051	-10000	0	-0.11	31	31
MMP3	0.035	0.007	-10000	0	0	21	21
APAF-1/Caspase 9	-0.023	0.04	-10000	0	-0.21	6	6

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.019	0.024	-10000	0	-0.13	10	10
alphaV beta3 Integrin	0.06	0.049	-10000	0	-0.13	27	27
PTK2	0.011	0.09	0.24	10	-0.29	20	30
IGF1R	0.033	0.011	-10000	0	0	53	53
PI4KB	0	0	-10000	0	-10000	0	0
MFGE8	0.036	0.006	-10000	0	0	16	16
SRC	0.034	0.009	-10000	0	0	34	34
CDKN1B	0	0.093	-10000	0	-0.32	38	38
VEGFA	0	0	-10000	0	-10000	0	0
ILK	0.011	0.072	-10000	0	-0.3	24	24
ROCK1	0.036	0.006	-10000	0	0	15	15
AKT1	-0.003	0.069	0.2	1	-0.31	21	22
PTK2B	-0.003	0.073	0.18	50	-0.19	4	54
alphaV/beta3 Integrin/JAM-A	0.071	0.047	0.18	7	-0.12	20	27
CBL	0.036	0.005	-10000	0	0	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.062	0.044	-10000	0	-0.13	24	24
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.069	0.068	-10000	0	-0.14	44	44
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.006	0.057	-10000	0	-0.28	11	11
alphaV/beta3 Integrin/Syndecan-1	0.055	0.043	-10000	0	-0.13	16	16
PI4KA	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.05	0.084	-10000	0	-0.15	67	67
PI4 Kinase	0	0	-10000	0	-10000	0	0
PIK3CA	0.031	0.014	-10000	0	0	82	82
alphaV/beta3 Integrin/Osteopontin	0.047	0.071	-10000	0	-0.14	59	59
RPS6KB1	-0.046	0.064	0.24	3	-0.21	19	22
TLN1	0.029	0.015	-10000	0	0	101	101
MAPK3	0.001	0.086	-10000	0	-0.35	23	23
GPR124	0.035	0.008	-10000	0	0	24	24
MAPK1	-0.002	0.088	-10000	0	-0.36	23	23
PXN	0.036	0.004	-10000	0	0	7	7
PIK3R1	0.032	0.012	-10000	0	0	63	63
alphaV/beta3 Integrin/Tumstatin	0.064	0.044	-10000	0	-0.13	24	24
cell adhesion	0.049	0.053	-10000	0	-0.16	26	26
ANGPTL3	0.036	0.005	-10000	0	0	9	9
VEGFR2 homodimer/VEGFA homodimer/Src	0.035	0.029	-10000	0	-0.12	9	9
IGF-1R heterotetramer	0.033	0.011	-10000	0	0	53	53
Rac1/GDP	0.017	0.02	-10000	0	-0.13	5	5
TGFBR2	0.035	0.009	-10000	0	0	29	29
ITGB3	0.036	0.003	-10000	0	0	4	4
IGF1	0.035	0.007	-10000	0	0	21	21
RAC1	0.025	0.017	-10000	0	0	163	163
regulation of cell-matrix adhesion	0.059	0.045	-10000	0	-0.13	24	24
apoptosis	0.034	0.009	-10000	0	0	31	31
CD47	0.035	0.008	-10000	0	0	24	24
alphaV/beta3 Integrin/CD47	0.06	0.048	-10000	0	-0.13	26	26
VCL	0.026	0.017	-10000	0	0	154	154
alphaV/beta3 Integrin/Del1	0.063	0.044	-10000	0	-0.13	24	24
CSF1	0.036	0.004	-10000	0	0	7	7
PIK3C2A	0.01	0.018	-10000	0	-0.097	2	2
PI4 Kinase/Pyk2	0.026	0.042	-10000	0	-0.12	29	29
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.046	0.051	-10000	0	-0.13	28	28
FAK1/Vinculin	0.014	0.077	0.24	7	-0.27	15	22
alphaV beta3/Integrin/ppsTEM5	0.06	0.045	-10000	0	-0.13	24	24
RHOA	0.035	0.007	-10000	0	0	21	21
VTN	0.036	0.004	-10000	0	0	5	5
BCAR1	0	0	-10000	0	-10000	0	0
FGF2	0.035	0.008	-10000	0	0	25	25
F11R	-0.012	0.033	0.093	44	-10000	0	44
alphaV/beta3 Integrin/Lactadherin	0.061	0.046	-10000	0	-0.13	24	24
alphaV/beta3 Integrin/TGFBR2	0.059	0.047	-10000	0	-0.13	27	27
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.06	0.04	-10000	0	-0.11	24	24
HSP90AA1	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.047	0.05	-10000	0	-0.12	31	31
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.035	0.009	-10000	0	0	30	30
alphaV/beta3 Integrin/Pyk2	0.064	0.062	0.19	45	-0.12	28	73
SDC1	0.031	0.014	-10000	0	0	82	82
VAV3	-0.026	0.03	0.18	2	-0.19	5	7
PTPN11	0.036	0.005	-10000	0	0	11	11
IRS1	0.033	0.011	-10000	0	0	51	51
FAK1/Paxillin	0.028	0.084	0.23	10	-0.25	20	30
cell migration	-0.003	0.071	0.22	7	-0.28	10	17
ITGAV	0.035	0.009	-10000	0	0	31	31
PI3K	0.055	0.087	-10000	0	-0.14	67	67
SPP1	0.033	0.011	-10000	0	0	54	54
KDR	0.029	0.015	-10000	0	0	103	103
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.034	0.009	-10000	0	0	31	31
COL4A3	0.037	0	-10000	0	-10000	0	0
angiogenesis	-0.001	0.095	-10000	0	-0.37	26	26
Rac1/GTP	-0.026	0.035	0.18	1	-0.18	6	7
EDIL3	0.036	0.003	-10000	0	0	4	4
cell proliferation	0.058	0.047	-10000	0	-0.12	27	27

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	0.026	0.16	-10000	0	-0.52	14	14
RAD9A	0.036	0.005	-10000	0	0	9	9
AP1	0.009	0.083	-10000	0	-0.18	72	72
IFNAR2	0.033	0.021	-10000	0	-0.035	37	37
AKT1	0.013	0.056	-10000	0	-0.26	19	19
ER alpha/Oestrogen	0.024	0.014	-10000	0	-10000	0	0
NFX1/SIN3/HDAC complex	-0.006	0.085	-10000	0	-0.27	33	33
EGF	0.033	0.016	-10000	0	-0.015	46	46
SMG5	0	0	-10000	0	-10000	0	0
SMG6	0	0	-10000	0	-10000	0	0
SP3/HDAC2	0.038	0.053	-10000	0	-0.17	22	22
TERT/c-Abl	0.033	0.16	-10000	0	-0.51	19	19
SAP18	0.034	0.01	-10000	0	0	43	43
MRN complex	0.069	0.024	-10000	0	-0.13	4	4
WT1	0.033	0.021	-10000	0	-0.035	37	37
WRN	0.035	0.009	-10000	0	0	29	29
SP1	0.034	0.023	-10000	0	-0.043	37	37
SP3	0.034	0.016	-10000	0	-0.031	26	26
TERF2IP	0.034	0.01	-10000	0	0	39	39
Telomerase/Nucleolin	0.039	0.16	-10000	0	-0.49	19	19
Mad/Max	0.047	0.028	-10000	0	-10000	0	0
TERT	0.023	0.16	-10000	0	-0.56	11	11
CCND1	-0.016	0.29	-10000	0	-0.95	40	40
MAX	0.032	0.018	-10000	0	-0.03	30	30
RBBP7	0.036	0.005	-10000	0	0	8	8
RBBP4	0.033	0.012	-10000	0	0	57	57
TERF2	0.028	0.011	0.084	6	-10000	0	6
PTGES3	0.036	0.006	-10000	0	0	15	15
SIN3A	0	0.001	-10000	0	-10000	0	0
Telomerase/911	0.048	0.1	-10000	0	-0.41	14	14
CDKN1B	-0.028	0.084	0.1	35	-0.34	27	62
RAD1	0.035	0.007	-10000	0	0	18	18
XRCC5	0.036	0.005	-10000	0	0	9	9
XRCC6	0.034	0.01	-10000	0	0	40	40
SAP30	0.036	0.007	-10000	0	0	18	18
TRF2/PARP2	0.032	0.058	-10000	0	-0.14	47	47
UBE3A	0.035	0.012	-10000	0	-0.023	19	19
JUN	0.032	0.016	-10000	0	-0.03	18	18
E6	0	0.003	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.025	0.021	-10000	0	-0.11	5	5
FOS	0.024	0.02	-10000	0	-0.03	16	16
IFN-gamma/IRF1	0.033	0.07	-10000	0	-0.19	39	39
PARP2	0.035	0.008	-10000	0	0	23	23
BLM	0.029	0.015	-10000	0	0	106	106
Telomerase	0.016	0.055	-10000	0	-0.32	9	9
IRF1	0.025	0.04	0.093	1	-0.1	35	36
ESR1	0.035	0.009	-10000	0	0	30	30
KU/TER	0.047	0.029	-10000	0	-0.14	9	9
ATM/TRF2	0.044	0.028	-10000	0	-0.1	9	9
ubiquitin-dependent protein catabolic process	0.003	0.083	-10000	0	-0.28	25	25
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.002	0.085	-10000	0	-0.29	25	25
HDAC1	0.035	0.007	-10000	0	0	21	21
HDAC2	0.03	0.024	-10000	0	-0.042	34	34
ATM	0.022	0.038	0.13	38	-0.18	5	43
SMAD3	-0.014	0.028	0.091	28	-10000	0	28
ABL1	0.032	0.013	-10000	0	0	69	69
MXD1	0.034	0.016	-10000	0	-0.03	30	30
MRE11A	0.036	0.005	-10000	0	0	8	8
HUS1	0.025	0.017	-10000	0	0	165	165
RPS6KB1	0.036	0.005	-10000	0	0	9	9
TERT/NF kappa B1/14-3-3	0.041	0.17	-10000	0	-0.53	17	17
NR2F2	0.022	0.023	-10000	0	-0.03	52	52
MAPK3	-0.017	0.017	0.094	2	-10000	0	2
MAPK1	-0.014	0.022	0.097	10	-10000	0	10
TGFB1/TGF beta receptor Type II	0.032	0.012	-10000	0	0	66	66
NFKB1	0.035	0.007	-10000	0	0	18	18
HNRNPC	0	0	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.022	0.038	0.13	38	-0.18	5	43
NBN	0.036	0.006	-10000	0	0	13	13
EGFR	0.009	0.016	-10000	0	0	380	380
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.005	0.057	-10000	0	-0.14	64	64
MYC	0.028	0.019	-10000	0	-0.029	20	20
IL2	0.034	0.023	-10000	0	-0.043	37	37
KU	0.047	0.029	-10000	0	-0.14	9	9
RAD50	0.036	0.006	-10000	0	0	12	12
HSP90AA1	0	0	-10000	0	-10000	0	0
TGFB1	0.032	0.012	-10000	0	0	66	66
TRF2/BLM	0.01	0.08	-10000	0	-0.15	94	94
FRAP1	0.036	0.006	-10000	0	0	16	16
KU/TERT	0.049	0.16	-10000	0	-0.51	15	15
SP1/HDAC2	0.042	0.047	-10000	0	-0.14	14	14
PINX1	0	0	-10000	0	-10000	0	0
Telomerase/EST1A	0.022	0.14	-10000	0	-0.46	19	19
Smad3/Myc	0.01	0.053	-10000	0	-0.13	51	51
911 complex	0.047	0.039	-10000	0	-0.13	4	4
IFNG	0.027	0.04	0.093	1	-0.11	35	36
Telomerase/PinX1	0.022	0.14	-10000	0	-0.46	19	19
Telomerase/AKT1/mTOR/p70S6K	0.022	0.094	0.22	1	-0.43	11	12
SIN3B	0.035	0.009	-10000	0	0	33	33
YWHAE	0.035	0.008	-10000	0	0	27	27
Telomerase/EST1B	0.022	0.14	-10000	0	-0.46	19	19
response to DNA damage stimulus	0.009	0.018	-10000	0	-0.084	11	11
MRN complex/TRF2/Rap1	0.076	0.073	-10000	0	-0.14	41	41
TRF2/WRN	0.034	0.046	-10000	0	-0.12	40	40
Telomerase/hnRNP C1/C2	0.022	0.14	-10000	0	-0.46	19	19
E2F1	0.032	0.021	-10000	0	-0.035	35	35
ZNFX1	0	0.001	-10000	0	-10000	0	0
PIF1	0	0	-10000	0	-10000	0	0
NCL	0.036	0.007	-10000	0	0	17	17
DKC1	0.035	0.007	-10000	0	0	18	18
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by PRL

Figure S94. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S94. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.033	0.012	-10000	0	0	57	57
mol:Halofuginone	-0.002	0.03	-10000	0	-0.17	15	15
ITGA1	0	0	-10000	0	-10000	0	0
CDKN1A	-0.026	0.15	-10000	0	-0.42	57	57
PRL-3/alpha Tubulin	0.018	0.033	-10000	0	-0.13	21	21
mol:Ca2+	-0.017	0.044	0.26	11	-10000	0	11
AGT	0.029	0.015	-10000	0	0	109	109
CCNA2	-0.025	0.12	-10000	0	-0.6	14	14
TUBA1B	0	0	-10000	0	-10000	0	0
EGR1	0.001	0.06	-10000	0	-0.33	15	15
CDK2/Cyclin E1	-0.003	0.15	-10000	0	-0.37	59	59
MAPK3	-0.013	0.03	0.093	37	-10000	0	37
PRL-2 /Rab GGTase beta	0.047	0.035	-10000	0	-0.16	12	12
MAPK1	-0.01	0.032	0.093	42	-10000	0	42
PTP4A1	-0.023	0.1	-10000	0	-0.62	14	14
PTP4A3	0.031	0.013	-10000	0	0	75	75
PTP4A2	0.036	0.006	-10000	0	0	16	16
ITGB1	-0.009	0.026	0.093	27	-10000	0	27
SRC	0.034	0.009	-10000	0	0	34	34
RAC1	-0.004	0.091	-10000	0	-0.39	22	22
Rab GGTase beta/Rab GGTase alpha	0.045	0.032	-10000	0	-0.14	11	11
PRL-1/ATF-5	-0.029	0.11	0.3	2	-0.57	15	17
RABGGTA	0.034	0.01	-10000	0	0	41	41
BCAR1	-0.009	0.055	0.25	21	-10000	0	21
RHOC	-0.008	0.12	-10000	0	-0.39	37	37
RHOA	-0.009	0.13	-10000	0	-0.44	35	35
cell motility	-0.003	0.13	0.26	1	-0.4	33	34
PRL-1/alpha Tubulin	-0.036	0.1	-10000	0	-0.56	15	15
PRL-3/alpha1 Integrin	0.018	0.033	-10000	0	-0.13	21	21
ROCK1	-0.002	0.13	0.26	1	-0.4	33	34
RABGGTB	0.035	0.008	-10000	0	0	25	25
CDK2	0.034	0.01	-10000	0	0	40	40
mitosis	-0.023	0.1	-10000	0	-0.61	14	14
ATF5	0.034	0.009	-10000	0	0	34	34

×

Aurora B signaling

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
Condensin I complex	0.001	0.013	-10000	0	-0.092	9	9
STMN1	-0.015	0.028	0.092	30	-10000	0	30
Aurora B/RasGAP/Survivin	0.034	0.076	-10000	0	-0.14	73	73
Chromosomal passenger complex/Cul3 protein complex	-0.033	0.078	-10000	0	-0.2	66	66
BIRC5	0.029	0.015	-10000	0	0	111	111
DES	0.025	0.093	-10000	0	-0.64	9	9
Aurora C/Aurora B/INCENP	0.063	0.021	-10000	0	-10000	0	0
Aurora B/TACC1	0.042	0.026	-10000	0	-0.12	9	9
Aurora B/PP2A	0.05	0.016	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	-0.001	0.05	-10000	0	-0.19	28	28
mitotic metaphase/anaphase transition	-0.001	0.003	0.009	22	-0.009	1	23
NDC80	-0.01	0.006	0.012	16	-10000	0	16
Cul3 protein complex	0.027	0.033	-10000	0	-0.14	8	8
KIF2C	-0.019	0.12	-10000	0	-0.44	35	35
PEBP1	-0.001	0.003	0.009	17	-0.009	11	28
KIF20A	0.029	0.015	-10000	0	0	110	110
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.04	0.045	-10000	0	-0.15	25	25
SEPT1	0	0	-10000	0	-10000	0	0
SMC2	0	0	-10000	0	-10000	0	0
SMC4	0	0	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.001	0.08	-10000	0	-0.48	9	9
PSMA3	0.034	0.01	-10000	0	0	37	37
G2/M transition of mitotic cell cycle	-0.001	0.002	0.008	13	-0.006	1	14
H3F3B	0.009	0.032	-10000	0	-0.2	11	11
AURKB	0.032	0.015	-10000	0	-0.009	55	55
AURKC	0.036	0.006	-10000	0	0	15	15
CDCA8	0.032	0.013	-10000	0	-0.003	59	59
cytokinesis	-0.026	0.15	0.19	6	-0.41	53	59
Aurora B/Septin1	-0.014	0.14	0.19	4	-0.38	54	58
AURKA	-0.001	0.002	0.008	13	-0.006	1	14
INCENP	0.034	0.014	0.058	1	-0.024	26	27
KLHL13	0	0	-10000	0	-10000	0	0
BUB1	0.036	0.006	0.058	1	0	11	12
hSgo1/Aurora B/Survivin	0.021	0.051	-10000	0	-0.11	58	58
EVI5	0.036	0.007	-10000	0	0	16	16
RhoA/GTP	0.01	0.13	-10000	0	-0.32	54	54
SGOL1	0	0	-10000	0	-10000	0	0
CENPA	-0.005	0.079	0.13	1	-0.28	33	34
NCAPG	0	0	-10000	0	-10000	0	0
Aurora B/HC8 Proteasome	0.045	0.03	-10000	0	-0.15	8	8
NCAPD2	0	0	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.048	0.026	-10000	0	-0.15	6	6
RHOA	0.035	0.007	-10000	0	0	21	21
NCAPH	0	0	-10000	0	-10000	0	0
NPM1	0.005	0.068	-10000	0	-0.31	17	17
RASA1	0.035	0.009	-10000	0	0	30	30
KLHL9	0.021	0.018	-10000	0	0	213	213
mitotic prometaphase	-0.001	0.003	0.009	17	-0.009	11	28
proteasomal ubiquitin-dependent protein catabolic process	0.045	0.03	-10000	0	-0.15	8	8
PPP1CC	0.036	0.005	-10000	0	0	9	9
Centraspindlin	0.001	0.13	-10000	0	-0.34	53	53
RhoA/GDP	0.024	0.019	-10000	0	-0.13	7	7
NSUN2	0.002	0.042	-10000	0	-0.29	9	9
MYLK	-0.015	0.07	-10000	0	-0.2	63	63
KIF23	0.029	0.018	-10000	0	-0.006	101	101
VIM	-0.013	0.02	0.089	12	-10000	0	12
RACGAP1	0.03	0.016	-10000	0	-0.003	88	88
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.003	0.065	-10000	0	-0.28	23	23
Chromosomal passenger complex	-0.016	0.1	0.14	5	-0.25	61	66
Chromosomal passenger complex/EVI5	0.061	0.086	-10000	0	-0.15	57	57
TACC1	0.035	0.008	-10000	0	0	23	23
PPP2R5D	0.036	0.004	-10000	0	0	5	5
CUL3	0.037	0.002	-10000	0	0	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.041	0.01	-10000	0	-10000	0	0
RGS9BP	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0	0	-10000	0	-10000	0	0
mol:Na +	0.009	0.061	-10000	0	-0.12	88	88
mol:ADP	0	0	-10000	0	-10000	0	0
GNAT2	0.036	0.004	-10000	0	0	7	7
RGS9-1/Gbeta5/R9AP	0.046	0.015	-10000	0	-0.12	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.047	0.012	-10000	0	-10000	0	0
GRK7	0	0	-10000	0	-10000	0	0
CNGB3	0.036	0.005	-10000	0	0	8	8
Cone Metarhodopsin II/X-Arrestin	0.027	0	-10000	0	-10000	0	0
mol:Ca2+	-0.014	0.056	0.18	2	-0.11	71	73
Cone PDE6	0.053	0.048	-10000	0	-0.11	1	1
Cone Metarhodopsin II	0	0	-10000	0	-10000	0	0
Na + (4 Units)	0.016	0.065	-10000	0	-0.11	87	87
GNAT2/GDP	0.059	0.021	-10000	0	-0.1	1	1
GNB5	0.035	0.007	-10000	0	0	22	22
mol:GMP (4 units)	-0.011	0.033	0.18	13	-10000	0	13
Cone Transducin	0.045	0.011	-10000	0	-10000	0	0
SLC24A2	0.029	0.015	-10000	0	0	101	101
GNB3/GNGT2	0.026	0.005	-10000	0	-10000	0	0
GNB3	0.035	0.007	-10000	0	0	20	20
GNAT2/GTP	0.027	0.003	-10000	0	-10000	0	0
CNGA3	0.022	0.018	-10000	0	0	199	199
ARR3	0.037	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.01	0.062	-10000	0	-0.12	88	88
mol:Pi	0.045	0.015	-10000	0	-0.12	1	1
Cone CNG Channel	0.025	0.076	-10000	0	-0.11	84	84
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.029	0.015	-10000	0	0	101	101
RGS9	0.035	0.007	-10000	0	0	18	18
PDE6C	0.025	0.017	-10000	0	0	157	157
GNGT2	0	0	-10000	0	-10000	0	0
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.035	0.008	-10000	0	0	23	23

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

Figure S97. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S97. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.033	0.011	-10000	0	0	48	48
NFATC1	0.004	0.1	-10000	0	-0.39	24	24
NFATC2	-0.036	0.084	-10000	0	-0.16	121	121
NFATC3	0.01	0.02	-10000	0	-0.1	14	14
YWHAE	0.035	0.008	-10000	0	0	27	27
Calcineurin A alpha-beta B1/CABIN1	-0.008	0.076	0.16	4	-0.23	24	28
Exportin 1/Ran/NUP214	0.068	0.03	-10000	0	-0.16	6	6
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.019	0.091	-10000	0	-0.22	21	21
BCL2/BAX	0.047	0.024	-10000	0	-0.14	4	4
CaM/Ca2+/Calcineurin A alpha-beta B1	0.02	0.027	-10000	0	-0.13	14	14
CaM/Ca2+	0.02	0.027	-10000	0	-0.13	14	14
BAX	0.034	0.01	-10000	0	0	43	43
MAPK14	0.036	0.004	-10000	0	0	5	5
BAD	0.036	0.006	-10000	0	0	13	13
CABIN1/MEF2D	0.006	0.082	-10000	0	-0.22	23	23
Calcineurin A alpha-beta B1/BCL2	0.035	0.007	-10000	0	0	20	20
FKBP8	0.035	0.009	-10000	0	0	31	31
activation-induced cell death of T cells	-0.006	0.081	0.22	23	-10000	0	23
KPNB1	0.035	0.008	-10000	0	0	23	23
KPNA2	0.034	0.01	-10000	0	0	40	40
XPO1	0.036	0.004	-10000	0	0	5	5
SFN	0.031	0.013	-10000	0	0	80	80
MAP3K8	0.022	0.018	-10000	0	0	200	200
NFAT4/CK1 alpha	0.024	0.044	0.17	1	-0.16	17	18
MEF2D/NFAT1/Cbp/p300	0.009	0.11	0.23	1	-0.21	35	36
CABIN1	-0.008	0.076	0.16	4	-0.23	24	28
CALM1	0.033	0.012	-10000	0	0	57	57
RAN	0.036	0.005	-10000	0	0	10	10
MAP3K1	0.035	0.007	-10000	0	0	20	20
CAMK4	0.036	0.005	-10000	0	0	8	8
mol:Ca2+	0	0.001	-10000	0	-10000	0	0
MAPK3	0.036	0.003	-10000	0	0	4	4
YWHAH	0.031	0.013	-10000	0	0	73	73
Calcineurin A alpha-beta B1/AKAP79/PKA	0.049	0.016	-10000	0	-10000	0	0
YWHAB	0.034	0.01	-10000	0	0	41	41
MAPK8	0.026	0.017	-10000	0	0	143	143
MAPK9	0.036	0.006	-10000	0	0	13	13
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0.032	0.012	-10000	0	0	63	63
NFAT1-c-4/YWHAQ	0	0.11	-10000	0	-0.38	20	20
PRKCH	0.034	0.01	-10000	0	0	42	42
CABIN1/Cbp/p300	0.047	0.028	-10000	0	-0.14	7	7
CASP3	0.034	0.009	-10000	0	0	32	32
PIM1	0.036	0.005	-10000	0	0	8	8
Calcineurin A alpha-beta B1/FKBP12/FK506	0.02	0.02	-10000	0	-0.11	10	10
apoptosis	0.019	0.035	-10000	0	-0.17	11	11
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.001	0.097	-10000	0	-0.31	27	27
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.037	0.003	-10000	0	0	3	3
JNK2/NFAT4	0.026	0.035	-10000	0	-0.12	19	19
BAD/BCL-XL	0.046	0.027	-10000	0	-0.14	6	6
PRKCD	0.034	0.01	-10000	0	0	40	40
NUP214	0.035	0.007	-10000	0	0	18	18
PRKCZ	0	0	-10000	0	-10000	0	0
PRKCA	0.036	0.004	-10000	0	0	6	6
PRKCG	0.037	0	-10000	0	-10000	0	0
PRKCQ	0.025	0.017	-10000	0	0	165	165
FKBP38/BCL2	0.049	0.016	-10000	0	-10000	0	0
EP300	0.033	0.011	-10000	0	0	50	50
PRKCB1	0.031	0.014	-10000	0	0	82	82
CSNK2A1	0.033	0.011	-10000	0	0	51	51
NFATc/JNK1	0.01	0.1	-10000	0	-0.38	22	22
CaM/Ca2+/FKBP38	0.039	0.031	-10000	0	-0.12	14	14
FKBP12/FK506	0.021	0.024	-10000	0	-0.13	10	10
CSNK1A1	-0.016	0.022	0.088	12	-0.12	10	22
CaM/Ca2+/CAMK IV	0.041	0.03	-10000	0	-0.12	13	13
NFATc/ERK1	0.022	0.1	-10000	0	-0.38	22	22
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.018	0.093	-10000	0	-0.22	22	22
NR4A1	-0.025	0.08	0.16	9	-0.2	25	34
GSK3B	0.034	0.01	-10000	0	0	39	39
positive T cell selection	0.01	0.02	-10000	0	-0.1	14	14
NFAT1/CK1 alpha	-0.021	0.07	-10000	0	-0.18	45	45
RCH1/ KPNB1	0.035	0.059	-10000	0	-0.15	44	44
YWHAQ	0.036	0.005	-10000	0	0	8	8
PRKACA	0.035	0.008	-10000	0	0	24	24
AKAP5	0.034	0.009	-10000	0	0	32	32
MEF2D	0.036	0.006	-10000	0	0	12	12
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.035	0.007	-10000	0	0	21	21
NFATc/p38 alpha	0.021	0.1	-10000	0	-0.38	22	22
CREBBP	0.036	0.005	-10000	0	0	9	9
BCL2	0.035	0.007	-10000	0	0	20	20

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.035	0.008	-10000	0	0	26	26
mol:S1P	0.001	0.002	0.019	3	-10000	0	3
S1P1/S1P/Gi	-0.02	0.11	-10000	0	-0.37	32	32
GNAO1	0.031	0.014	-10000	0	-10000	0	0
S1P/S1P3/G12/G13	0.024	0.038	-10000	0	-0.1	28	28
AKT1	-0.014	0.16	-10000	0	-0.48	47	47
AKT3	0.01	0.077	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.035	0.008	-10000	0	0	26	26
GNAI2	0.034	0.011	-10000	0	-10000	0	0
GNAI3	0.037	0.006	-10000	0	-10000	0	0
GNAI1	0.018	0.019	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.001	0.002	0.019	3	-10000	0	3
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	0.034	0.01	-10000	0	0	45	45
mol:Ca2+	-0.002	0.1	0.2	1	-0.29	36	37
MAPK3	-0.009	0.099	0.18	1	-0.28	37	38
MAPK1	-0.003	0.093	0.18	1	-0.28	30	31
JAK2	-0.01	0.11	0.21	5	-0.32	40	45
CXCR4	-0.007	0.099	0.18	1	-0.28	39	40
FLT1	0.036	0.01	-10000	0	-10000	0	0
RhoA/GDP	0.024	0.019	-10000	0	-0.13	7	7
Rac1/GDP	0.017	0.02	-10000	0	-0.13	5	5
SRC	-0.009	0.097	-10000	0	-0.29	35	35
S1P/S1P3/Gi	-0.002	0.1	0.2	1	-0.29	36	37
RAC1	0.025	0.017	-10000	0	0	163	163
RhoA/GTP	0.01	0.11	0.18	1	-0.27	40	41
VEGFA	0.002	0.002	0.032	3	-10000	0	3
S1P/S1P2/Gi	-0.006	0.1	0.16	1	-0.26	47	48
VEGFR1 homodimer/VEGFA homodimer	0.029	0.01	0.11	3	-10000	0	3
RHOA	0.035	0.007	-10000	0	0	21	21
S1P/S1P3/Gq	0.015	0.04	-10000	0	-0.15	26	26
GNAQ	0.035	0.009	-10000	0	0	30	30
GNAZ	0.032	0.014	-10000	0	-10000	0	0
G12/G13	0.025	0.048	-10000	0	-0.14	28	28
GNA14	0.035	0.009	-10000	0	0	29	29
GNA15	0.033	0.011	-10000	0	0	51	51
GNA12	0.023	0.018	-10000	0	0	189	189
GNA13	0.035	0.007	-10000	0	0	20	20
GNA11	0.033	0.011	-10000	0	0	51	51
Rac1/GTP	0	0.092	-10000	0	-0.31	23	23

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.029	0.015	-10000	0	0	109	109
positive regulation of NF-kappaB transcription factor activity	0.035	0.046	-10000	0	-0.14	25	25
MAP2K4	0.015	0.06	0.21	2	-0.29	8	10
IKBKB	0.036	0.003	-10000	0	0	4	4
TNFRSF10B	0.035	0.008	-10000	0	0	25	25
TNFRSF10A	0	0	-10000	0	-10000	0	0
SMPD1	0.014	0.028	-10000	0	-0.11	20	20
IKBKG	0.037	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.036	0.006	-10000	0	0	12	12
TRAIL/TRAILR2	0.034	0.045	-10000	0	-0.14	24	24
TRAIL/TRAILR3	0.035	0.046	-10000	0	-0.14	25	25
TRAIL/TRAILR1	0.014	0.036	-10000	0	-0.13	26	26
TRAIL/TRAILR4	0.035	0.046	-10000	0	-0.14	25	25
TRAIL/TRAILR1/DAP3/GTP	0.029	0.04	-10000	0	-0.11	33	33
IKK complex	-0.034	0.12	-10000	0	-0.22	135	135
RIPK1	0.035	0.007	-10000	0	0	20	20
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.023	0.025	-10000	0	-0.13	12	12
MAPK3	-0.005	0.039	0.093	68	-10000	0	68
MAP3K1	0.022	0.055	-10000	0	-0.28	7	7
TRAILR4 (trimer)	0.036	0.006	-10000	0	0	12	12
TRADD	0.036	0.005	-10000	0	0	10	10
TRAILR1 (trimer)	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.018	0.049	-10000	0	-0.17	23	23
CFLAR	0.036	0.005	-10000	0	0	8	8
MAPK1	-0.004	0.039	0.093	68	-10000	0	68
TRAIL/TRAILR1/FADD/TRADD/RIP	0.07	0.048	-10000	0	-0.11	25	25
mol:ceramide	0.014	0.028	-10000	0	-0.11	20	20
FADD	0.036	0.006	-10000	0	0	12	12
MAPK8	0.007	0.047	0.19	1	-0.28	6	7
TRAF2	0.036	0.006	-10000	0	0	16	16
TRAILR3 (trimer)	0.036	0.006	-10000	0	0	14	14
CHUK	0.025	0.017	-10000	0	0	165	165
TRAIL/TRAILR1/FADD	0.033	0.039	-10000	0	-0.12	25	25
DAP3	0.035	0.008	-10000	0	0	23	23
CASP10	-0.004	0.052	0.14	16	-0.17	22	38
JNK cascade	0.035	0.046	-10000	0	-0.14	25	25
TRAIL (trimer)	0.029	0.015	-10000	0	0	109	109
TNFRSF10C	0.036	0.006	-10000	0	0	14	14
TRAIL/TRAILR1/DAP3/GTP/FADD	0.042	0.047	-10000	0	-0.11	32	32
TRAIL/TRAILR2/FADD	0.05	0.048	-10000	0	-0.12	23	23
cell death	0.014	0.028	-10000	0	-0.11	20	20
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.024	0.05	-10000	0	-0.25	4	4
TRAILR2 (trimer)	0.035	0.008	-10000	0	0	25	25
CASP8	0.016	0.023	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.087	0.057	-10000	0	-0.12	22	22

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.044	0.039	-10000	0	-0.14	18	18
ATM	0.034	0.01	-10000	0	0	37	37
UBE2D3	0.036	0.006	-10000	0	0	12	12
PRKDC	0.034	0.01	-10000	0	0	45	45
ATR	0.035	0.008	-10000	0	0	25	25
UBE2L3	0.034	0.009	-10000	0	0	32	32
FANCD2	0.008	0.036	-10000	0	-0.2	14	14
protein ubiquitination	0.077	0.056	-10000	0	-0.13	22	22
XRCC5	0.036	0.005	-10000	0	0	9	9
XRCC6	0.034	0.01	-10000	0	0	40	40
M/R/N Complex	0.069	0.024	-10000	0	-0.13	4	4
MRE11A	0.036	0.005	-10000	0	0	8	8
DNA-PK	0.056	0.05	-10000	0	-0.14	23	23
FA complex/FANCD2/Ubiquitin	0.003	0.084	-10000	0	-0.3	22	22
FANCF	0.035	0.008	-10000	0	0	26	26
BRCA1	0.036	0.006	-10000	0	0	12	12
CCNE1	0.033	0.012	-10000	0	0	57	57
CDK2/Cyclin E1	0.045	0.023	-10000	0	-0.14	2	2
FANCG	0.031	0.014	-10000	0	0	85	85
BRCA1/BACH1/BARD1	0.046	0.038	-10000	0	-0.14	19	19
FANCE	0.036	0.003	-10000	0	0	4	4
FANCC	0.036	0.006	-10000	0	0	15	15
NBN	0.036	0.006	-10000	0	0	13	13
FANCA	0.036	0.007	-10000	0	0	17	17
DNA repair	-0.013	0.085	0.21	10	-0.33	11	21
BRCA1/BARD1/ubiquitin	0.046	0.038	-10000	0	-0.14	19	19
BARD1/DNA-PK	0.069	0.066	-10000	0	-0.14	35	35
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.044	0.039	0.14	18	-10000	0	18
BRCA1/BARD1/CTIP/M/R/N Complex	0.01	0.064	-10000	0	-0.22	27	27
BRCA1/BACH1/BARD1/TopBP1	0.051	0.062	-10000	0	-0.14	46	46
BRCA1/BARD1/P53	0.066	0.069	-10000	0	-0.13	47	47
BARD1/CSTF1/BRCA1	0.061	0.042	-10000	0	-0.13	18	18
BRCA1/BACH1	0.036	0.006	-10000	0	0	12	12
BARD1	0.035	0.007	-10000	0	0	21	21
PCNA	0.032	0.012	-10000	0	0	62	62
BRCA1/BARD1/UbcH5C	0.063	0.043	-10000	0	-0.14	20	20
BRCA1/BARD1/UbcH7	0.059	0.048	-10000	0	-0.13	24	24
BRCA1/BARD1/RAD51/PCNA	0.069	0.062	-10000	0	-0.13	33	33
BARD1/DNA-PK/P53	0.067	0.084	-10000	0	-0.14	58	58
BRCA1/BARD1/Ubiquitin	0.046	0.038	-10000	0	-0.14	19	19
BRCA1/BARD1/CTIP	0.04	0.059	-10000	0	-0.14	44	44
FA complex	0.013	0.058	-10000	0	-0.2	23	23
BARD1/EWS	0.043	0.039	-10000	0	-0.14	19	19
RBBP8	-0.013	0.029	0.093	34	-10000	0	34
TP53	0.031	0.013	-10000	0	0	73	73
TOPBP1	0.033	0.011	-10000	0	0	51	51
G1/S transition of mitotic cell cycle	-0.064	0.068	0.13	47	-10000	0	47
BRCA1/BARD1	0.085	0.06	-10000	0	-0.13	22	22
CSTF1	0.034	0.009	-10000	0	0	33	33
BARD1/EWS-Fli1	0.021	0.031	-10000	0	-0.13	19	19
CDK2	0.034	0.01	-10000	0	0	40	40
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.035	0.007	-10000	0	0	21	21
RAD50	0.036	0.006	-10000	0	0	12	12
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.046	0.038	-10000	0	-0.14	19	19
EWSR1	0.034	0.009	-10000	0	0	34	34

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.024	0.1	-10000	0	-0.48	17	17
SMARCC2	0.034	0.01	-10000	0	0	44	44
SMARCC1	0.034	0.009	-10000	0	0	33	33
TBX21	0.032	0.055	0.34	1	-10000	0	1
SUMO2	0.033	0.019	0.071	1	-0.03	35	36
STAT1 (dimer)	0.036	0.039	0.11	22	-0.17	14	36
FKBP4	0.034	0.009	-10000	0	0	34	34
FKBP5	0.028	0.016	-10000	0	0	118	118
GR alpha/HSP90/FKBP51/HSP90	-0.025	0.065	-10000	0	-0.18	12	12
PRL	0.039	0.058	0.54	1	-10000	0	1
cortisol/GR alpha (dimer)/TIF2	-0.042	0.12	-10000	0	-0.32	2	2
RELA	0.015	0.11	0.18	32	-0.16	127	159
FGG	-0.049	0.1	-10000	0	-0.32	2	2
GR beta/TIF2	-0.024	0.076	-10000	0	-0.2	5	5
IFNG	0.036	0.083	0.36	1	-10000	0	1
apoptosis	-0.022	0.2	0.44	27	-0.49	37	64
CREB1	0.043	0.01	-10000	0	-10000	0	0
histone acetylation	0.022	0.055	0.22	1	-0.21	2	3
BGLAP	0.04	0.062	0.3	1	-10000	0	1
GR/PKAc	0.021	0.092	-10000	0	-0.19	18	18
NF kappa B1 p50/RelA	0.03	0.18	0.3	30	-0.26	119	149
SMARCD1	0.035	0.007	-10000	0	0	20	20
MDM2	-0.008	0.036	-10000	0	-10000	0	0
GATA3	0.031	0.021	-10000	0	-10000	0	0
AKT1	0.028	0.03	0.16	8	-0.091	18	26
CSF2	0.006	0.032	-10000	0	-10000	0	0
GSK3B	0.032	0.02	0.071	1	-0.03	32	33
NR1I3	-0.014	0.18	0.45	18	-0.48	21	39
CSN2	-0.046	0.09	0.26	1	-0.29	2	3
BRG1/BAF155/BAF170/BAF60A	0.064	0.074	-10000	0	-0.17	38	38
NFATC1	0.041	0.008	-10000	0	-10000	0	0
POU2F1	0.04	0.012	-10000	0	-10000	0	0
CDKN1A	-0.12	0.41	-10000	0	-1.2	59	59
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.008	0.029	26	-10000	0	26
SFN	0.031	0.013	-10000	0	0	80	80
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.011	0.069	-10000	0	-0.16	4	4
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.07	0.28	0.43	18	-0.66	72	90
JUN	0.024	0.053	0.36	3	-10000	0	3
IL4	0.036	0.053	-10000	0	-10000	0	0
CDK5R1	0.035	0.009	-10000	0	0	25	25
PRKACA	0.035	0.008	-10000	0	0	24	24
cortisol/GR alpha (monomer)/AP-1	-0.049	0.053	-10000	0	-0.23	12	12
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.005	0.074	-10000	0	-0.16	18	18
cortisol/GR alpha (monomer)	-0.057	0.12	-10000	0	-0.37	2	2
NCOA2	0.036	0.006	-10000	0	0	12	12
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	0.039	0.032	0.17	7	-10000	0	7
AP-1/NFAT1-c-4	0.047	0.077	0.45	2	-10000	0	2
AFP	0.024	0.067	-10000	0	-10000	0	0
SUV420H1	0.033	0.011	-10000	0	0	50	50
IRF1	-0.029	0.13	-10000	0	-0.66	15	15
TP53	-0.013	0.17	-10000	0	-0.49	56	56
PPP5C	0.034	0.01	-10000	0	0	39	39
KRT17	0.041	0.082	0.4	2	-10000	0	2
KRT14	0.031	0.068	-10000	0	-10000	0	0
TBP	0.042	0.018	-10000	0	-10000	0	0
CREBBP	0.029	0.018	-10000	0	-0.094	10	10
HDAC1	0.032	0.007	-10000	0	-10000	0	0
HDAC2	0.032	0.011	-10000	0	-10000	0	0
AP-1	0.048	0.077	0.45	2	-10000	0	2
MAPK14	0.034	0.019	-10000	0	-0.03	33	33
MAPK10	0.029	0.021	0.073	1	-0.03	27	28
MAPK11	0.03	0.021	0.071	1	-0.03	32	33
KRT5	0.04	0.08	0.46	1	-10000	0	1
interleukin-1 receptor activity	-0.001	0	-10000	0	-10000	0	0
NCOA1	0.033	0.018	0.077	1	-0.067	9	10
STAT1	0.036	0.039	0.11	22	-0.17	14	36
CGA	0.036	0.055	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.034	0.071	-10000	0	-0.37	7	7
MAPK3	0.034	0.02	0.075	2	-0.03	38	40
MAPK1	0.031	0.02	-10000	0	-0.03	32	32
ICAM1	0.03	0.14	0.34	16	-10000	0	16
NFKB1	0.016	0.11	0.18	30	-0.16	119	149
MAPK8	0.034	0.059	0.34	1	-10000	0	1
MAPK9	0.033	0.019	-10000	0	-0.03	32	32
cortisol/GR alpha (dimer)	-0.024	0.2	0.44	26	-0.51	38	64
BAX	-0.033	0.18	-10000	0	-0.85	10	10
POMC	0.032	0.075	0.48	1	-10000	0	1
EP300	0.026	0.019	-10000	0	-0.094	10	10
cortisol/GR alpha (dimer)/p53	-0.071	0.13	-10000	0	-0.41	19	19
proteasomal ubiquitin-dependent protein catabolic process	-0.005	0.069	0.24	31	-10000	0	31
SGK1	-0.017	0.06	-10000	0	-0.24	14	14
IL13	0.028	0.064	-10000	0	-10000	0	0
IL6	0.031	0.13	0.34	19	-10000	0	19
PRKACG	0.036	0.005	-10000	0	0	10	10
IL5	0.021	0.072	0.41	1	-10000	0	1
IL2	0.041	0.077	-10000	0	-10000	0	0
CDK5	0.024	0.018	-10000	0	0	185	185
PRKACB	0.033	0.011	-10000	0	0	48	48
HSP90AA1	0	0	-10000	0	-10000	0	0
IL8	-0.11	0.4	0.34	18	-0.79	126	144
CDK5R1/CDK5	0.029	0.042	-10000	0	-0.14	17	17
NF kappa B1 p50/RelA/PKAc	0.056	0.17	0.3	28	-0.21	111	139
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.038	0.11	-10000	0	-0.34	2	2
SMARCA4	0.032	0.012	-10000	0	0	62	62
chromatin remodeling	-0.038	0.11	-10000	0	-0.37	28	28
NF kappa B1 p50/RelA/Cbp	0.046	0.16	0.3	21	-0.22	110	131
JUN (dimer)	0.024	0.053	0.36	3	-10000	0	3
YWHAH	0.031	0.013	-10000	0	0	73	73
VIPR1	0.035	0.065	0.38	5	-10000	0	5
NR3C1	-0.04	0.086	-10000	0	-0.35	1	1
NR4A1	0.039	0.009	-10000	0	-10000	0	0
TIF2/SUV420H1	0.036	0.055	-10000	0	-0.14	42	42
MAPKKK cascade	-0.022	0.2	0.44	27	-0.49	37	64
cortisol/GR alpha (dimer)/Src-1	-0.049	0.12	-10000	0	-0.37	3	3
PBX1	0.04	0.01	-10000	0	-10000	0	0
POU1F1	0.041	0.011	-10000	0	-10000	0	0
SELE	0.027	0.13	0.34	2	-10000	0	2
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.038	0.11	-10000	0	-0.38	28	28
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.038	0.11	-10000	0	-0.34	2	2
mol:cortisol	-0.035	0.061	-10000	0	-0.2	1	1
MMP1	0.038	0.073	0.36	1	-0.49	3	4

×

Coregulation of Androgen receptor activity

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
NRIP1	0.035	0.01	-10000	0	-10000	0	0
SVIL	0.024	0.018	-10000	0	-10000	0	0
ZNF318	0.035	0.005	-10000	0	-0.045	1	1
JMJD2C	0.036	0.014	-10000	0	-10000	0	0
T-DHT/AR/Ubc9	0.053	0.041	-10000	0	-10000	0	0
CARM1	0.035	0.008	-10000	0	0	28	28
PRDX1	0.035	0.007	-10000	0	0	20	20
PELP1	0.035	0.007	-10000	0	0	17	17
CTNNB1	0.036	0.006	-10000	0	-10000	0	0
AKT1	0.032	0.012	-10000	0	-0.001	55	55
PTK2B	0.036	0.007	-10000	0	0	16	16
MED1	0	0	-10000	0	-10000	0	0
MAK	0.033	0.009	-10000	0	-0.045	1	1
response to oxidative stress	0	0	-10000	0	-10000	0	0
HIP1	0.022	0.018	-10000	0	-10000	0	0
GSN	0.032	0.013	-10000	0	-10000	0	0
NCOA2	0.036	0.006	-10000	0	0	12	12
NCOA6	0.033	0.012	-10000	0	-10000	0	0
DNA-PK	0.055	0.05	-10000	0	-0.15	22	22
NCOA4	0.026	0.017	-10000	0	0	147	147
PIAS3	0.036	0.006	-10000	0	-10000	0	0
cell proliferation	0.023	0.045	-10000	0	-0.45	4	4
XRCC5	0.036	0.005	-10000	0	0	9	9
UBE3A	0.038	0.003	-10000	0	-10000	0	0
T-DHT/AR/SNURF	0.032	0.033	0.12	1	-0.071	33	34
FHL2	0.018	0.2	-10000	0	-0.69	33	33
RANBP9	0.036	0.007	-10000	0	-10000	0	0
JMJD1A	0.044	0.012	-10000	0	-10000	0	0
CDK6	0.024	0.017	-10000	0	0	177	177
TGFB1I1	0.033	0.012	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	0.034	0.057	-10000	0	-0.1	54	54
XRCC6	0.034	0.01	-10000	0	0	40	40
T-DHT/AR	0.049	0.06	0.22	1	-0.13	33	34
CTDSP1	0.036	0.006	-10000	0	0	15	15
CTDSP2	0.031	0.012	-10000	0	-0.038	1	1
BRCA1	0.037	0.006	-10000	0	-10000	0	0
TCF4	0.032	0.012	-10000	0	-0.034	1	1
CDKN2A	0.004	0.012	-10000	0	0	448	448
SRF	0.04	0.056	0.11	90	-0.15	33	123
NKX3-1	0.026	0.07	-10000	0	-0.28	21	21
KLK3	0.016	0.047	-10000	0	-10000	0	0
TMF1	0.036	0.007	-10000	0	0	18	18
HNRNPA1	-0.001	0	-10000	0	-10000	0	0
AOF2	0.034	0.011	-10000	0	-10000	0	0
APPL1	-0.011	0.004	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	0.05	0.041	-10000	0	-0.08	33	33
AR	0.036	0.031	-10000	0	-0.069	33	33
UBA3	0	0	-10000	0	-10000	0	0
PATZ1	-0.001	0	-10000	0	-10000	0	0
PAWR	0.036	0.006	-10000	0	0	13	13
PRKDC	0.033	0.01	-10000	0	0	45	45
PA2G4	0.034	0.008	-10000	0	-0.032	1	1
UBE2I	0.036	0.004	-10000	0	0	6	6
T-DHT/AR/Cyclin D3/CDK11 p58	0.045	0.044	0.14	1	-0.079	42	43
RPS6KA3	0.036	0.007	-10000	0	-10000	0	0
T-DHT/AR/ARA70	0.038	0.046	-10000	0	-0.087	20	20
LATS2	-0.001	0	-10000	0	-10000	0	0
T-DHT/AR/PRX1	0.046	0.043	0.14	1	-0.08	39	40
Cyclin D3/CDK11 p58	0.021	0.028	-10000	0	-0.14	16	16
VAV3	0.029	0.015	-10000	0	-10000	0	0
KLK2	0.025	0.057	-10000	0	-0.32	11	11
CASP8	0.036	0.006	-10000	0	0	13	13
T-DHT/AR/TIF2/CARM1	0.07	0.046	-10000	0	-0.11	1	1
TMPRSS2	0.026	0.071	-10000	0	-0.3	15	15
CCND1	0.029	0.015	-10000	0	0	111	111
PIAS1	0.036	0.008	-10000	0	-10000	0	0
mol:T-DHT	0.004	0.017	0.052	1	-0.049	33	34
CDC2L1	0	0	-10000	0	-10000	0	0
PIAS4	0.036	0.008	-10000	0	-10000	0	0
T-DHT/AR/CDK6	0.037	0.041	-10000	0	-0.081	8	8
CMTM2	0	0	-10000	0	-10000	0	0
SNURF	0	0	-10000	0	-10000	0	0
ZMIZ1	0.004	0.017	0.052	1	-0.049	33	34
CCND3	0.035	0.008	-10000	0	0	25	25
TGIF1	-0.001	0	-10000	0	-10000	0	0
FKBP4	0.035	0.009	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.018	0.091	-10000	0	-0.24	38	38
CaM/Ca2+	0.02	0.027	-10000	0	-0.13	14	14
AKT1	0.033	0.011	-10000	0	0	54	54
AKT2	0.035	0.008	-10000	0	0	28	28
STXBP4	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.002	0.089	0.17	2	-0.25	38	40
YWHAZ	0.035	0.007	-10000	0	0	21	21
CALM1	0.033	0.012	-10000	0	0	57	57
YWHAQ	0.036	0.005	-10000	0	0	8	8
TBC1D4	-0.016	0.021	0.093	16	-10000	0	16
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.031	0.013	-10000	0	0	73	73
YWHAB	0.034	0.01	-10000	0	0	41	41
SNARE/Synip	0.021	0.018	-10000	0	-0.11	8	8
YWHAG	0	0	-10000	0	-10000	0	0
ASIP	0.034	0.009	-10000	0	0	34	34
PRKCI	0.035	0.008	-10000	0	0	27	27
AS160/CaM/Ca2+	0.02	0.027	-10000	0	-0.13	14	14
RHOQ	0.036	0.006	-10000	0	0	16	16
GYS1	0.001	0.039	0.24	2	-0.21	6	8
PRKCZ	0	0	-10000	0	-10000	0	0
TRIP10	0.034	0.009	-10000	0	0	35	35
TC10/GTP/CIP4/Exocyst	0.042	0.03	-10000	0	-0.12	14	14
AS160/14-3-3	-0.005	0.098	-10000	0	-0.41	18	18
VAMP2	0.033	0.011	-10000	0	0	49	49
SLC2A4	-0.004	0.096	0.17	2	-0.27	40	42
STX4	0	0	-10000	0	-10000	0	0
GSK3B	0.004	0.077	-10000	0	-0.3	27	27
SFN	0.031	0.013	-10000	0	0	80	80
LNPEP	0.036	0.005	-10000	0	0	8	8
YWHAE	0.035	0.008	-10000	0	0	27	27

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.035	0.008	-10000	0	0	26	26
alphaV beta3 Integrin	0.044	0.043	-10000	0	-0.14	24	24
PTK2	0.012	0.11	-10000	0	-0.33	29	29
positive regulation of JNK cascade	0.021	0.09	-10000	0	-0.28	18	18
CDC42/GDP	0.036	0.12	-10000	0	-0.34	34	34
Rac1/GDP	0.029	0.1	-10000	0	-0.36	11	11
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.036	0.005	-10000	0	0	10	10
CTNNB1	0.036	0.006	-10000	0	0	15	15
CDC42/GTP	0.029	0.11	-10000	0	-0.35	18	18
nectin-3/I-afadin	0.044	0.027	-10000	0	-0.14	5	5
RAPGEF1	0.005	0.12	-10000	0	-0.35	34	34
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.005	0.12	-10000	0	-0.39	34	34
PDGFB-D/PDGFRB	0.035	0.008	-10000	0	0	26	26
TLN1	-0.006	0.058	0.16	21	-0.23	13	34
Rap1/GTP	-0.001	0.083	-10000	0	-0.27	35	35
IQGAP1	0.033	0.011	-10000	0	0	47	47
Rap1/GTP/I-afadin	0.043	0.015	-10000	0	-0.1	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.044	0.027	-10000	0	-0.14	5	5
PVR	0.035	0.009	-10000	0	0	31	31
Necl-5(dimer)	0.034	0.009	-10000	0	0	31	31
mol:GDP	0.021	0.13	-10000	0	-0.41	29	29
MLLT4	0.034	0.009	-10000	0	0	34	34
PIK3CA	0.031	0.014	-10000	0	0	82	82
PI3K	0.057	0.09	-10000	0	-0.14	72	72
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.05	0.015	-10000	0	-10000	0	0
positive regulation of lamellipodium assembly	0.02	0.077	-10000	0	-0.28	12	12
PVRL1	0.036	0.005	-10000	0	0	8	8
PVRL3	0.032	0.012	-10000	0	0	60	60
PVRL2	0.034	0.009	-10000	0	0	35	35
PIK3R1	0.032	0.012	-10000	0	0	63	63
CDH1	0.034	0.01	-10000	0	0	37	37
CLDN1	0.034	0.009	-10000	0	0	36	36
JAM-A/CLDN1	0.074	0.045	-10000	0	-0.12	8	8
SRC	0.012	0.13	-10000	0	-0.41	34	34
ITGB3	0.036	0.003	-10000	0	0	4	4
nectin-1(dimer)/I-afadin/I-afadin	0.05	0.015	-10000	0	-10000	0	0
FARP2	0.026	0.14	-10000	0	-0.48	15	15
RAC1	0.025	0.017	-10000	0	0	163	163
CTNNA1	0.035	0.007	-10000	0	0	18	18
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.057	0.035	-10000	0	-0.12	5	5
nectin-1/I-afadin	0.05	0.015	-10000	0	-10000	0	0
nectin-2/I-afadin	0.047	0.023	-10000	0	-0.14	3	3
RAC1/GTP/IQGAP1/filamentous actin	0.024	0.043	-10000	0	-0.12	30	30
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.059	0.034	-10000	0	-0.12	5	5
CDC42/GTP/IQGAP1/filamentous actin	0.035	0.042	-10000	0	-0.12	33	33
F11R	0.033	0.011	-10000	0	0	52	52
positive regulation of filopodium formation	0.021	0.09	-10000	0	-0.28	18	18
alphaV/beta3 Integrin/Talin	0.031	0.087	0.22	26	-0.22	23	49
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.047	0.023	-10000	0	-0.14	3	3
nectin-2(dimer)/I-afadin/I-afadin	0.047	0.023	-10000	0	-0.14	3	3
PIP5K1C	-0.01	0.041	0.09	4	-0.21	15	19
VAV2	0.025	0.14	-10000	0	-0.45	20	20
RAP1/GDP	0.026	0.11	-10000	0	-0.31	35	35
ITGAV	0.035	0.009	-10000	0	0	31	31
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.056	0.038	-10000	0	-0.14	7	7
nectin-3(dimer)/I-afadin/I-afadin	0.044	0.027	-10000	0	-0.14	5	5
Rac1/GTP	0.026	0.093	-10000	0	-0.34	12	12
PTPRM	0.008	0.045	-10000	0	-0.23	16	16
E-cadherin/beta catenin/alpha catenin	0.083	0.059	-10000	0	-0.13	13	13
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.035	0.008	-10000	0	0	26	26

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	0.054	0.094	-10000	0	-0.2	46	46
Ran/GTP/Exportin 1/HDAC1	-0.029	0.022	-10000	0	-0.11	25	25
NF kappa B1 p50/RelA/I kappa B alpha	0.007	0.11	-10000	0	-0.27	47	47
SUMO1	0.036	0.003	-10000	0	0	4	4
ZFPM1	0	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.007	0.034	-10000	0	-0.15	21	21
FKBP3	0.034	0.009	-10000	0	0	35	35
Histones	0.035	0.076	-10000	0	-0.24	22	22
YY1/LSF	0.015	0.064	-10000	0	-0.22	19	19
SMG5	0	0	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	0	10	10
I kappa B alpha/HDAC3	0	0.078	-10000	0	-0.2	52	52
I kappa B alpha/HDAC1	0.008	0.097	-10000	0	-0.22	62	62
SAP18	0.034	0.01	-10000	0	0	43	43
RELA	-0.003	0.081	0.19	1	-0.28	18	19
HDAC1/Smad7	0.043	0.041	-10000	0	-0.13	6	6
RANGAP1	0.033	0.011	-10000	0	0	46	46
HDAC3/TR2	0.027	0.071	-10000	0	-0.26	20	20
NuRD/MBD3 Complex	-0.01	0.11	-10000	0	-0.33	38	38
NF kappa B1 p50/RelA	0.012	0.088	-10000	0	-0.29	18	18
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.035	0.008	-10000	0	0	23	23
GATA1	0.037	0	-10000	0	-10000	0	0
Mad/Max	0.051	0.014	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.008	0.11	-10000	0	-0.34	35	35
RBBP7	0.036	0.005	-10000	0	0	8	8
NPC	0.017	0.021	-10000	0	-0.09	18	18
RBBP4	0.033	0.012	-10000	0	0	57	57
MAX	0.034	0.009	-10000	0	0	32	32
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.035	0.007	-10000	0	0	22	22
NFKBIA	-0.001	0.082	-10000	0	-0.32	27	27
KAT2B	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	-0.007	0.09	-10000	0	-0.29	29	29
SIN3 complex	0.055	0.042	-10000	0	-0.13	17	17
SMURF1	0.025	0.017	-10000	0	0	164	164
CHD3	0.036	0.006	-10000	0	0	13	13
SAP30	0.035	0.007	-10000	0	0	18	18
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.035	0.008	-10000	0	0	27	27
YY1/HDAC3	-0.002	0.078	-10000	0	-0.24	31	31
YY1/HDAC2	0.014	0.061	-10000	0	-0.21	19	19
YY1/HDAC1	0.016	0.063	-10000	0	-0.22	19	19
NuRD/MBD2 Complex (MeCP1)	-0.004	0.095	-10000	0	-0.28	35	35
PPARG	0.002	0.078	-10000	0	-0.21	52	52
HDAC8/hEST1B	0.024	0.005	-10000	0	-10000	0	0
UBE2I	0.036	0.004	-10000	0	0	6	6
beta TrCP1/SCF ubiquitin ligase complex	0.035	0.007	-10000	0	0	22	22
TNFRSF1A	0.032	0.012	-10000	0	0	65	65
HDAC3/SMRT (N-CoR2)	0.027	0.071	-10000	0	-0.26	20	20
MBD3L2	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.043	0.04	-10000	0	-0.13	6	6
CREBBP	0.036	0.005	-10000	0	0	9	9
NuRD/MBD3/MBD3L2 Complex	-0.005	0.11	-10000	0	-0.33	34	34
HDAC1	0.035	0.007	-10000	0	0	21	21
HDAC3	0.006	0.064	-10000	0	-0.3	16	16
HDAC2	0.032	0.012	-10000	0	0	59	59
YY1	0.01	0.028	-10000	0	-0.21	7	7
HDAC8	0	0	-10000	0	-10000	0	0
SMAD7	0.034	0.01	-10000	0	0	45	45
NCOR2	0.037	0.002	-10000	0	0	2	2
MXD1	0.037	0.003	-10000	0	0	3	3
STAT3	0.006	0.06	-10000	0	-0.22	33	33
NFKB1	0.035	0.007	-10000	0	0	18	18
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.035	0.008	-10000	0	0	25	25
YY1/LSF/HDAC1	0.029	0.072	-10000	0	-0.22	19	19
YY1/SAP30/HDAC1	0.031	0.07	-10000	0	-0.21	19	19
EP300	0.033	0.011	-10000	0	0	50	50
STAT3 (dimer non-phopshorylated)	0.006	0.06	-10000	0	-0.22	33	33
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.082	-10000	0	-0.32	27	27
histone deacetylation	-0.004	0.095	-10000	0	-0.28	35	35
STAT3 (dimer non-phopshorylated)/HDAC3	-0.001	0.094	-10000	0	-0.31	29	29
nuclear export	-0.023	0.005	-10000	0	-10000	0	0
PRKACA	0.035	0.008	-10000	0	0	24	24
GATAD2B	0	0	-10000	0	-10000	0	0
GATAD2A	0.033	0.011	-10000	0	0	55	55
GATA2/HDAC3	0.026	0.07	-10000	0	-0.26	19	19
GATA1/HDAC1	0.051	0.023	-10000	0	-0.14	6	6
GATA1/HDAC3	0.027	0.071	-10000	0	-0.26	20	20
CHD4	0.034	0.01	-10000	0	0	37	37
TNF-alpha/TNFR1A	0.035	0.056	-10000	0	-0.14	43	43
SIN3/HDAC complex/Mad/Max	-0.004	0.085	-10000	0	-0.3	25	25
NuRD Complex	-0.003	0.11	-10000	0	-0.34	34	34
positive regulation of chromatin silencing	0.033	0.074	-10000	0	-0.24	22	22
SIN3B	0.034	0.009	-10000	0	0	33	33
MTA2	0.036	0.004	-10000	0	0	5	5
SIN3A	0	0	-10000	0	-10000	0	0
XPO1	0.036	0.004	-10000	0	0	5	5
SUMO1/HDAC1	0.036	0.056	-10000	0	-0.22	6	6
HDAC complex	0.066	0.073	-10000	0	-0.15	42	42
GATA1/Fog1	0.027	0	-10000	0	-10000	0	0
FKBP25/HDAC1/HDAC2	0.054	0.05	-10000	0	-0.14	22	22
TNF	0.036	0.003	-10000	0	0	4	4
negative regulation of cell growth	-0.004	0.085	-10000	0	-0.29	26	26
NuRD/MBD2/PRMT5 Complex	-0.004	0.095	-10000	0	-0.28	35	35
Ran/GTP/Exportin 1	0.036	0.06	-10000	0	-0.16	21	21
NF kappa B/RelA/I kappa B alpha	-0.005	0.093	-10000	0	-0.25	52	52
SIN3/HDAC complex/NCoR1	-0.003	0.093	-10000	0	-0.33	24	24
TFCP2	0.035	0.008	-10000	0	0	25	25
NR2C1	0.036	0.003	-10000	0	0	4	4
MBD3	0.034	0.01	-10000	0	0	40	40
MBD2	0.036	0.007	-10000	0	0	17	17

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.011	0.002	0.001	22	-10000	0	22
SMARCC1	-0.005	0.12	-10000	0	-1.2	4	4
REL	0.036	0.004	-10000	0	-0.011	3	3
HDAC7	-0.03	0.057	0.17	5	-0.21	19	24
JUN	0.034	0.01	-10000	0	0	41	41
EP300	0.033	0.011	-10000	0	0	50	50
KAT2B	0	0	-10000	0	-10000	0	0
KAT5	0	0	-10000	0	-10000	0	0
MAPK14	-0.017	0.019	0.09	4	-10000	0	4
FOXO1	0	0	-10000	0	-10000	0	0
T-DHT/AR	0.018	0.079	0.25	2	-0.22	19	21
MAP2K6	0.035	0.013	-10000	0	-0.034	14	14
BRM/BAF57	0.047	0.024	-10000	0	-0.14	3	3
MAP2K4	0.034	0.015	-10000	0	-0.033	16	16
SMARCA2	0.032	0.013	-10000	0	0	68	68
PDE9A	-0.013	0.2	-10000	0	-0.8	28	28
NCOA2	0.036	0.006	-10000	0	0	12	12
CEBPA	0.028	0.016	-10000	0	0	121	121
EHMT2	0.037	0.002	-10000	0	0	1	1
cell proliferation	-0.019	0.093	0.26	7	-0.29	19	26
NR0B1	0.03	0.014	-10000	0	0	88	88
EGR1	0.029	0.015	-10000	0	0	107	107
RXRs/9cRA	0.067	0.018	-10000	0	-0.11	1	1
AR/RACK1/Src	-0.013	0.063	0.21	4	-0.22	2	6
AR/GR	0.002	0.061	0.16	1	-0.2	25	26
GNB2L1	0.037	0.002	-10000	0	0	2	2
PKN1	0.033	0.011	-10000	0	0	48	48
RCHY1	0.036	0.006	-10000	0	0	16	16
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	-0.011	0.02	0.089	7	-10000	0	7
T-DHT/AR/TIF2/CARM1	0.014	0.057	0.21	5	-0.2	4	9
SRC	-0.02	0.037	0.18	10	-10000	0	10
NR3C1	0.035	0.007	-10000	0	0	22	22
KLK3	-0.003	0.074	0.37	2	-0.33	2	4
APPBP2	0.034	0.015	-10000	0	-0.034	16	16
TRIM24	0.024	0.018	-10000	0	0	182	182
T-DHT/AR/TIP60	-0.024	0.028	0.082	2	-0.15	10	12
TMPRSS2	0.017	0.081	-10000	0	-0.56	7	7
RXRG	0.036	0.006	-10000	0	0	14	14
mol:9cRA	0	0	0.002	1	-10000	0	1
RXRA	0.035	0.007	-10000	0	0	21	21
RXRB	0.037	0.002	-10000	0	0	1	1
CARM1	0.035	0.008	-10000	0	0	28	28
NR2C2	0.036	0.005	-10000	0	0	8	8
KLK2	-0.002	0.046	0.21	1	-0.25	1	2
AR	-0.004	0.044	0.15	5	-0.2	17	22
SENP1	0	0	0.003	1	-10000	0	1
HSP90AA1	0	0	-10000	0	-10000	0	0
MDM2	0.033	0.011	-10000	0	-0.001	46	46
SRY	0.036	0.004	-10000	0	-0.009	4	4
GATA2	0.035	0.008	-10000	0	0	23	23
MYST2	0.034	0.01	-10000	0	0	37	37
HOXB13	0.037	0.003	-10000	0	0	4	4
T-DHT/AR/RACK1/Src	-0.015	0.064	0.19	12	-0.23	2	14
positive regulation of transcription	0.035	0.008	-10000	0	0	23	23
DNAJA1	0.032	0.017	-10000	0	-0.034	16	16
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.037	-10000	0	-0.26	8	8
NCOA1	0.037	0.034	0.14	3	-0.27	4	7
SPDEF	0.037	0.003	-10000	0	0	4	4
T-DHT/AR/TIF2	-0.032	0.085	0.19	2	-0.24	42	44
T-DHT/AR/Hsp90	-0.024	0.028	0.082	2	-0.15	10	12
GSK3B	0.034	0.01	-10000	0	0	39	39
NR2C1	0.036	0.003	-10000	0	0	4	4
mol:T-DHT	-0.018	0.035	0.17	9	-0.12	4	13
SIRT1	0.024	0.017	-10000	0	0	174	174
ZMIZ2	-0.001	0.001	-10000	0	-0.02	1	1
POU2F1	0.037	0.035	0.12	13	-0.11	22	35
T-DHT/AR/DAX-1	-0.021	0.038	0.2	2	-0.18	4	6
CREBBP	0.036	0.005	-10000	0	0	9	9
SMARCE1	0.037	0.004	-10000	0	0	7	7

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.009	0.14	0.34	1	-1	8	9
VDR	0.035	0.007	-10000	0	0	21	21
FAM120B	0	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.012	0.099	0.25	2	-0.27	41	43
RXRs/LXRs/DNA/Oxysterols	0.005	0.14	0.31	2	-0.4	46	48
MED1	0	0	-10000	0	-10000	0	0
mol:9cRA	0	0.016	0.043	4	-0.047	46	50
RARs/THRs/DNA/Src-1	0.016	0.054	-10000	0	-0.21	6	6
RXRs/NUR77	0.079	0.065	-10000	0	-0.12	32	32
RXRs/PPAR	0.019	0.048	-10000	0	-0.18	6	6
NCOR2	0.037	0.002	-10000	0	0	2	2
VDR/VDR/Vit D3	0.026	0.005	-10000	0	-10000	0	0
RARs/VDR/DNA/Vit D3	0.081	0.024	-10000	0	-10000	0	0
RARA	0.037	0.003	-10000	0	0	3	3
NCOA1	0.033	0.011	-10000	0	0	49	49
VDR/VDR/DNA	0.035	0.007	-10000	0	0	21	21
RARs/RARs/DNA/9cRA	0.056	0.032	-10000	0	-10000	0	0
RARG	0.036	0.005	-10000	0	0	11	11
RPS6KB1	-0.004	0.087	0.51	8	-0.4	8	16
RARs/THRs/DNA/SMRT	0.03	0.025	-10000	0	-0.18	4	4
THRA	0.036	0.006	-10000	0	0	12	12
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.026	0.005	-10000	0	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	0.058	0.074	0.29	3	-0.16	39	42
NR1H4	0.036	0.004	-10000	0	0	6	6
RXRs/LXRs/DNA	0.085	0.1	0.31	2	-0.22	38	40
NR1H2	0.029	0.031	0.091	2	-0.062	46	48
NR1H3	0.03	0.033	0.093	2	-0.069	44	46
RXRs/VDR/DNA/Vit D3	0.071	0.061	0.21	1	-0.11	35	36
NR4A1	0.036	0.006	-10000	0	0	14	14
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.016	0.04	0.13	1	-0.14	6	7
RXRG	0.03	0.03	0.089	2	-0.06	46	48
RXR alpha/CCPG	0.023	0.021	-10000	0	-0.065	6	6
RXRA	0.03	0.03	0.089	2	-0.061	44	46
RXRB	0.031	0.033	0.09	2	-0.066	49	51
THRB	0.036	0.004	-10000	0	0	7	7
PPARG	0.035	0.008	-10000	0	0	26	26
PPARD	0.037	0.002	-10000	0	0	1	1
TNF	-0.001	0.13	-10000	0	-0.4	38	38
mol:Oxysterols	0	0.015	0.039	5	-0.042	49	54
cholesterol transport	0.005	0.14	0.31	2	-0.4	46	48
PPARA	0.034	0.01	-10000	0	0	44	44
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.036	0.005	-10000	0	0	10	10
RXRs/NUR77/BCL2	0.02	0.03	-10000	0	-0.15	2	2
SREBF1	-0.01	0.17	0.35	2	-0.51	39	41
RXRs/RXRs/DNA/9cRA	0.058	0.074	0.28	3	-0.16	39	42
ABCA1	-0.044	0.26	0.35	2	-0.82	48	50
RARs/THRs	0.1	0.027	-10000	0	-0.12	1	1
RXRs/FXR	0.079	0.065	0.22	1	-0.12	36	37
BCL2	0.035	0.007	-10000	0	0	20	20

×

IL27-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.032	0.012	-10000	0	0	66	66
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.002	0.067	0.44	3	-10000	0	3
IL27/IL27R/JAK1	0.041	0.062	-10000	0	-10000	0	0
TBX21	-0.015	0.092	0.35	18	-10000	0	18
IL12B	0.037	0.004	-10000	0	0	6	6
IL12A	-0.011	0.002	0.014	2	-10000	0	2
IL6ST	0.034	0.011	-10000	0	-0.033	1	1
IL27RA/JAK1	0.026	0.046	-10000	0	-10000	0	0
IL27	-0.001	0.004	-10000	0	-10000	0	0
TYK2	0.034	0.011	-10000	0	-0.033	1	1
T-helper cell lineage commitment	0.063	0.083	0.18	150	-0.18	2	152
T-helper 2 cell differentiation	0.002	0.067	0.44	3	-10000	0	3
T cell proliferation during immune response	0.002	0.067	0.44	3	-10000	0	3
MAPKKK cascade	-0.002	0.067	-10000	0	-0.44	3	3
STAT3	0.034	0.01	-10000	0	0	37	37
STAT2	0.036	0.006	-10000	0	0	13	13
STAT1	0.034	0.01	-10000	0	0	40	40
IL12RB1	0.035	0.008	-10000	0	0	26	26
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.016	0.09	0.35	17	-10000	0	17
IL27/IL27R/JAK2/TYK2	-0.002	0.067	-10000	0	-0.45	3	3
positive regulation of T cell mediated cytotoxicity	-0.002	0.067	-10000	0	-0.44	3	3
STAT1 (dimer)	0.048	0.081	-10000	0	-0.34	5	5
JAK2	0.03	0.014	-10000	0	-0.032	1	1
JAK1	0.034	0.01	-10000	0	0	40	40
STAT2 (dimer)	0.014	0.099	-10000	0	-0.35	9	9
T cell proliferation	0.003	0.062	-10000	0	-0.32	4	4
IL12/IL12R/TYK2/JAK2	0.011	0.18	-10000	0	-0.77	24	24
IL17A	0.061	0.082	0.18	143	-0.18	2	145
mast cell activation	0.002	0.067	0.44	3	-10000	0	3
IFNG	0.003	0.029	-10000	0	-0.088	23	23
T cell differentiation	-0.001	0.003	-10000	0	-0.017	9	9
STAT3 (dimer)	0.011	0.11	-10000	0	-0.38	12	12
STAT5A (dimer)	0.015	0.1	-10000	0	-0.35	10	10
STAT4 (dimer)	0.014	0.098	-10000	0	-0.38	6	6
STAT4	0.035	0.009	-10000	0	0	29	29
T cell activation	-0.005	0.005	-10000	0	-0.086	1	1
IL27R/JAK2/TYK2	0.038	0.063	-10000	0	-10000	0	0
GATA3	0.007	0.092	0.67	9	-10000	0	9
IL18	-0.01	0.004	0	74	-10000	0	74
positive regulation of mast cell cytokine production	0.011	0.11	-10000	0	-0.38	12	12
IL27/EBI3	0.025	0.011	-10000	0	-10000	0	0
IL27RA	0.002	0.027	-10000	0	-10000	0	0
IL6	0.02	0.018	-10000	0	0	236	236
STAT5A	0.036	0.004	-10000	0	0	5	5
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.007	0.028	0.35	1	-10000	0	1
IL1B	-0.009	0.005	0	101	-10000	0	101
EBI3	0.034	0.011	-10000	0	-0.033	1	1
TNF	-0.011	0.001	0	4	-10000	0	4

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.007	0.034	0.093	48	-10000	0	48
MAP4K4	0.003	0.053	-10000	0	-0.21	11	11
BAG4	0.036	0.005	-10000	0	0	11	11
PKC zeta/ceramide	0.004	0.048	-10000	0	-0.23	12	12
NFKBIA	0.033	0.012	-10000	0	0	57	57
BIRC3	0.031	0.014	-10000	0	0	82	82
BAX	0.002	0.075	-10000	0	-0.32	23	23
RIPK1	0.035	0.007	-10000	0	0	20	20
AKT1	-0.012	0.04	0.38	3	-10000	0	3
BAD	-0.003	0.048	-10000	0	-0.24	11	11
SMPD1	-0.003	0.054	0.13	3	-0.19	22	25
RB1	-0.003	0.048	0.21	1	-0.23	12	13
FADD/Caspase 8	0.015	0.051	-10000	0	-0.24	6	6
MAP2K4	-0.006	0.053	0.2	4	-0.23	12	16
NSMAF	0.035	0.009	-10000	0	0	29	29
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.009	0.052	0.2	7	-0.24	11	18
EGF	0.035	0.008	-10000	0	0	25	25
mol:ceramide	0.005	0.052	-10000	0	-0.24	12	12
MADD	0.036	0.006	-10000	0	0	15	15
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.007	0.035	0.093	51	-10000	0	51
ASAH1	0.036	0.007	-10000	0	0	17	17
negative regulation of cell cycle	-0.002	0.048	0.2	1	-0.23	12	13
cell proliferation	0.02	0.054	0.22	1	-0.24	4	5
BID	0.004	0.15	-10000	0	-0.58	26	26
MAP3K1	0	0.051	0.14	2	-0.24	12	14
EIF2A	-0.009	0.05	0.2	5	-0.22	12	17
TRADD	0.036	0.005	-10000	0	0	10	10
CRADD	0.036	0.005	-10000	0	0	11	11
MAPK3	-0.006	0.049	0.19	7	-0.25	4	11
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.014	0.063	0.19	7	-0.22	20	27
Cathepsin D/ceramide	0.021	0.056	-10000	0	-0.24	12	12
FADD	0.009	0.047	-10000	0	-0.22	5	5
KSR1	-0.003	0.048	-10000	0	-0.24	12	12
MAPK8	-0.04	0.095	0.18	1	-0.19	104	105
PRKRA	-0.005	0.052	0.23	2	-0.23	13	15
PDGFA	0.027	0.016	-10000	0	0	134	134
TRAF2	0.036	0.006	-10000	0	0	16	16
IGF1	0.035	0.007	-10000	0	0	21	21
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	0.005	0.051	-10000	0	-0.24	12	12
CTSD	0.033	0.011	-10000	0	0	56	56
regulation of nitric oxide biosynthetic process	0.05	0.025	-10000	0	-0.14	7	7
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.022	0.058	0.24	1	-0.26	4	5
PRKCD	0.034	0.01	-10000	0	0	40	40
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.007	0.035	0.093	51	-10000	0	51
RelA/NF kappa B1	0.05	0.025	-10000	0	-0.14	7	7
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.036	0.006	-10000	0	0	13	13
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.018	0.054	-10000	0	-0.24	7	7
TNFR1A/BAG4/TNF-alpha	0.053	0.056	-10000	0	-0.13	41	41
mol:Sphingosine-1-phosphate	-0.007	0.034	0.093	48	-10000	0	48
MAP2K1	-0.016	0.051	0.18	7	-0.23	11	18
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.036	0.004	-10000	0	0	7	7
CYCS	0.025	0.062	0.14	22	-0.18	11	33
TNFRSF1A	0.032	0.012	-10000	0	0	65	65
NFKB1	0.035	0.007	-10000	0	0	18	18
TNFR1A/BAG4	0.035	0.055	-10000	0	-0.14	42	42
EIF2AK2	-0.01	0.053	0.21	5	-0.22	13	18
TNF-alpha/TNFR1A/FAN	0.047	0.067	-10000	0	-0.14	55	55
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.034	0.049	-10000	0	-0.27	4	4
MAP2K2	-0.008	0.052	0.19	17	-0.32	2	19
SMPD3	0.007	0.054	0.16	1	-0.27	8	9
TNF	0.036	0.003	-10000	0	0	4	4
PKC zeta/PAR4	0.026	0.004	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.006	0.044	0.13	8	-0.15	14	22
NF kappa B1/RelA/I kappa B alpha	0.07	0.048	-10000	0	-0.12	20	20
AIFM1	-0.003	0.049	0.14	2	-0.19	18	20
BCL2	0.035	0.007	-10000	0	0	20	20

×

E-cadherin signaling events

Figure S110. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S110. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.063	0.03	-9999	-0.13	3	3
E-cadherin/beta catenin	0.048	0.022	-9999	-0.14	3	3
CTNNB1	0.036	0.006	-9999	0	15	15
JUP	0.033	0.011	-9999	0	51	51
CDH1	0.034	0.01	-9999	0	37	37

×

Atypical NF-kappaB 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
BCL3/RelA	0.05	0.018	-10000	0	-0.14	2	2
FBXW11	0.035	0.007	-10000	0	0	22	22
NF kappa B1 p50/c-Rel	0.033	0.018	-10000	0	-0.13	5	5
NF kappa B1 p50/RelA/I kappa B alpha	0.026	0.07	0.18	2	-0.26	14	16
NFKBIA	0.005	0.059	-10000	0	-0.18	28	28
MAPK14	0.036	0.004	-10000	0	0	5	5
NF kappa B1 p105/p50	0.029	0.031	-10000	0	-0.13	16	16
ARRB2	0.012	0.025	-10000	0	-0.2	7	7
REL	0.037	0.002	-10000	0	0	2	2
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.031	0.019	-10000	0	-0.13	5	5
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.032	0.021	-10000	0	-0.13	7	7
PIK3CA	0.031	0.014	-10000	0	0	82	82
NF kappa B1 p50 dimer	-0.02	0.029	0.18	7	-0.14	5	12
PIK3R1	0.032	0.012	-10000	0	0	63	63
NFKB1	-0.021	0.011	0.093	4	-10000	0	4
RELA	0.036	0.004	-10000	0	0	7	7
positive regulation of anti-apoptosis	0.015	0.041	0.14	2	-0.14	22	24
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.027	0.073	0.18	2	-0.26	15	17
SRC	0.034	0.009	-10000	0	0	34	34
PI3K	0.018	0.076	-10000	0	-0.16	72	72
NF kappa B1 p50/RelA	0.015	0.041	0.14	2	-0.14	22	24
IKBKB	0.036	0.003	-10000	0	0	4	4
beta TrCP1/SCF ubiquitin ligase complex	0.035	0.007	-10000	0	0	22	22
SYK	0.031	0.013	-10000	0	0	74	74
I kappa B alpha/PIK3R1	0.018	0.073	0.22	1	-0.24	24	25
cell death	0.026	0.071	0.18	2	-0.25	15	17
NF kappa B1 p105/c-Rel	0.033	0.018	-10000	0	-0.13	5	5
LCK	0.035	0.007	-10000	0	0	18	18
BCL3	0.035	0.009	-10000	0	0	31	31

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.003	0.038	0.097	26	-0.11	10	36
NFATC2	-0.001	0.027	0.083	16	-0.098	12	28
NFATC3	-0.003	0.038	0.097	26	-0.11	12	38
CD40LG	0.01	0.11	0.35	17	-0.24	3	20
PTGS2	-0.021	0.068	0.38	1	-0.24	3	4
JUNB	0.031	0.014	-10000	0	0	84	84
CaM/Ca2+/Calcineurin A alpha-beta B1	0.026	0.028	-10000	0	-0.12	13	13
CaM/Ca2+	0.026	0.028	-10000	0	-0.12	13	13
CALM1	0.035	0.014	-10000	0	-10000	0	0
JUN	0.037	0.012	-10000	0	-10000	0	0
mol:Ca2+	0.001	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.021	0.02	-10000	0	-0.11	10	10
FOSL1	0.033	0.011	-10000	0	0	53	53
CREM	0.026	0.016	-10000	0	0	147	147
Jun/NFAT1-c-4/p21SNFT	0.056	0.071	0.26	13	-0.18	4	17
FOS	0.027	0.019	-10000	0	-10000	0	0
IFNG	0.009	0.11	0.36	15	-0.25	1	16
AP-1/NFAT1-c-4	0.09	0.12	0.37	7	-0.27	3	10
FASLG	0.009	0.11	0.34	16	-0.25	1	17
NFAT1-c-4/ICER1	0.039	0.051	0.21	11	-10000	0	11
IL2RA	0.001	0.086	0.37	3	-10000	0	3
FKBP12/FK506	0.021	0.024	-10000	0	-0.13	10	10
CSF2	0.009	0.11	0.34	16	-0.24	3	19
JunB/Fra1/NFAT1-c-4	0.055	0.06	0.22	6	-0.19	1	7
IL4	0.009	0.11	0.34	16	-0.25	1	17
IL2	0.013	0.086	-10000	0	-0.84	5	5
IL3	0.033	0.075	-10000	0	-0.58	7	7
FKBP1A	0.032	0.012	-10000	0	0	63	63
BATF3	0	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.039	0.008	-10000	0	-10000	0	0

×

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	0.06	0.039	-10000	0	-0.12	20	20
HDAC3	0.036	0.004	-10000	0	0	7	7
Ran/GTP/Exportin 1/HDAC4	-0.03	0.023	-10000	0	-0.11	35	35
GATA1/HDAC4	0.047	0.035	-10000	0	-0.14	15	15
GATA1/HDAC5	0.053	0.012	-10000	0	-0.14	1	1
GATA2/HDAC5	0.05	0.016	-10000	0	-0.14	1	1
HDAC5/BCL6/BCoR	0.052	0.051	-10000	0	-0.13	28	28
HDAC9	0.022	0.018	-10000	0	0	207	207
Glucocorticoid receptor/Hsp90/HDAC6	0.044	0.029	-10000	0	-0.12	15	15
HDAC4/ANKRA2	0.044	0.041	-10000	0	-0.15	20	20
HDAC5/YWHAB	0.047	0.029	-10000	0	-0.16	7	7
NPC/RanGAP1/SUMO1/Ubc9	0.007	0.034	-10000	0	-0.15	21	21
GATA2	0.035	0.008	-10000	0	0	23	23
HDAC4/RFXANK	0.038	0.05	-10000	0	-0.15	30	30
BCOR	0.034	0.009	-10000	0	0	35	35
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0	0	-10000	0	-10000	0	0
HDAC5	0.036	0.006	-10000	0	0	14	14
GNB1/GNG2	0.021	0.031	-10000	0	-0.13	20	20
Histones	0.023	0.066	-10000	0	-0.17	38	38
ADRBK1	0.036	0.005	-10000	0	0	10	10
HDAC4	0.035	0.009	-10000	0	0	30	30
XPO1	0.036	0.004	-10000	0	0	5	5
HDAC5/ANKRA2	0.05	0.025	-10000	0	-0.14	7	7
HDAC4/Ubc9	0.046	0.035	-10000	0	-0.14	15	15
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.047	0.031	-10000	0	-0.14	11	11
TUBA1B	0	0	-10000	0	-10000	0	0
HDAC6	0.037	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.044	0.039	-10000	0	-0.14	18	18
CAMK4	0.036	0.005	-10000	0	0	8	8
Tubulin/HDAC6	0.036	0.044	-10000	0	-0.12	38	38
SUMO1	0.036	0.003	-10000	0	0	4	4
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.034	0.01	-10000	0	0	41	41
GATA1	0.037	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.035	0.008	-10000	0	0	27	27
NR3C1	0.035	0.007	-10000	0	0	22	22
SUMO1/HDAC4	0.033	0.059	-10000	0	-0.24	6	6
SRF	0.037	0.002	-10000	0	0	1	1
HDAC4/YWHAB	0.041	0.043	-10000	0	-0.16	20	20
Tubulin	0.015	0.042	-10000	0	-0.13	38	38
HDAC4/14-3-3 E	0.042	0.045	-10000	0	-0.15	24	24
GNB1	0.035	0.007	-10000	0	0	20	20
RANGAP1	0.033	0.011	-10000	0	0	46	46
BCL6/BCoR	0.036	0.047	-10000	0	-0.14	28	28
HDAC4/HDAC3/SMRT (N-CoR2)	0.065	0.038	-10000	0	-0.13	16	16
HDAC4/SRF	0.066	0.036	-10000	0	-0.13	14	14
HDAC4/ER alpha	0.044	0.036	-10000	0	-0.14	15	15
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.023	0.066	-10000	0	-0.17	38	38
cell motility	0.036	0.044	-10000	0	-0.12	38	38
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.036	0.004	-10000	0	0	6	6
HDAC7/HDAC3	0.027	0.008	-10000	0	-0.13	1	1
BCL6	0.032	0.013	-10000	0	0	71	71
HDAC4/CaMK II delta B	0.035	0.009	-10000	0	0	30	30
Hsp90/HDAC6	0.027	0	-10000	0	-10000	0	0
ESR1	0.035	0.009	-10000	0	0	30	30
HDAC6/HDAC11	0.054	0.007	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.036	0.06	-10000	0	-0.16	21	21
NPC	0.017	0.021	-10000	0	-0.09	18	18
MEF2C	0.035	0.008	-10000	0	0	28	28
RAN	0.036	0.005	-10000	0	0	10	10
HDAC4/MEF2C	0.093	0.055	-10000	0	-0.12	26	26
GNG2	0	0	-10000	0	-10000	0	0
NCOR2	0.037	0.002	-10000	0	0	2	2
TUBB2A	0.034	0.01	-10000	0	0	45	45
HDAC11	0.036	0.005	-10000	0	0	8	8
HSP90AA1	0	0	-10000	0	-10000	0	0
RANBP2	0.035	0.008	-10000	0	0	25	25
ANKRA2	0.036	0.006	-10000	0	0	13	13
RFXANK	0.034	0.01	-10000	0	0	44	44
nuclear import	-0.028	0.059	0.21	26	-10000	0	26

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.036	0.007	-10000	0	0	17	17
ANTXR2	0	0	-10000	0	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0	-10000	0	-10000	0	0
monocyte activation	-0.068	0.16	-10000	0	-0.34	135	135
MAP2K2	0.019	0.039	-10000	0	-0.59	2	2
MAP2K1	-0.008	0.002	-10000	0	-10000	0	0
MAP2K7	-0.008	0.002	-10000	0	-10000	0	0
MAP2K6	-0.009	0.002	-10000	0	-10000	0	0
CYAA	-0.007	0.001	-10000	0	-10000	0	0
MAP2K4	-0.008	0.002	-10000	0	-10000	0	0
IL1B	0	0.04	0.081	71	-0.076	57	128
Channel	0.023	0.004	-10000	0	-10000	0	0
NLRP1	-0.001	0	-10000	0	-10000	0	0
CALM1	0.033	0.012	-10000	0	0	57	57
negative regulation of phagocytosis	-0.02	0.12	-10000	0	-0.41	44	44
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0	-10000	0	-10000	0	0
MAPK3	-0.009	0.002	-10000	0	-10000	0	0
MAPK1	-0.008	0.003	-10000	0	-10000	0	0
PGR	-0.009	0.002	-10000	0	-10000	0	0
PA/Cellular Receptors	0.024	0.004	-10000	0	-10000	0	0
apoptosis	-0.002	0	-10000	0	-10000	0	0
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.022	0.004	-10000	0	-10000	0	0
macrophage activation	-0.012	0.011	0.068	8	-10000	0	8
TNF	0.036	0.003	-10000	0	0	4	4
VCAM1	-0.068	0.16	-10000	0	-0.34	134	134
platelet activation	-0.02	0.12	-10000	0	-0.41	44	44
MAPKKK cascade	0.003	0.02	0.065	3	-0.069	29	32
IL18	-0.005	0.036	0.086	40	-0.076	60	100
negative regulation of macrophage activation	-0.002	0	-10000	0	-10000	0	0
LEF	-0.002	0	-10000	0	-10000	0	0
CASP1	0.003	0.004	0.025	13	-10000	0	13
mol:cAMP	-0.02	0.12	-10000	0	-0.41	44	44
necrosis	-0.002	0	-10000	0	-10000	0	0
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.022	0.004	-10000	0	-10000	0	0
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	0.047	0.065	-10000	0	-10000	0	0
MKNK1	0.034	0.009	-10000	0	0	35	35
MAPK14	0.047	0.037	0.16	3	-0.083	22	25
ATF2/c-Jun	-0.001	0.094	-10000	0	-0.32	32	32
MAPK11	0.043	0.039	0.16	3	-0.083	22	25
MITF	0.031	0.049	0.17	8	-0.2	7	15
MAPKAPK5	0.034	0.039	0.22	1	-10000	0	1
KRT8	0.035	0.04	0.18	8	-10000	0	8
MAPKAPK3	0.035	0.007	-10000	0	0	19	19
MAPKAPK2	0.034	0.01	-10000	0	0	43	43
p38alpha-beta/CK2	0.062	0.057	0.23	3	-10000	0	3
CEBPB	0.024	0.069	0.18	16	-0.21	26	42
SLC9A1	0.032	0.041	-10000	0	-0.26	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.031	0.055	0.26	4	-0.26	2	6
p38alpha-beta/MNK1	0.064	0.069	-10000	0	-0.15	18	18
JUN	-0.005	0.092	-10000	0	-0.33	31	31
PPARGC1A	0.032	0.057	0.23	2	-0.21	13	15
USF1	0.028	0.038	0.18	3	-10000	0	3
RAB5/GDP/GDI1	0.012	0.078	-10000	0	-0.22	26	26
NOS2	0.028	0.037	0.18	3	-10000	0	3
DDIT3	0.029	0.062	0.17	10	-0.2	20	30
RAB5A	0.034	0.009	-10000	0	0	32	32
HSPB1	0.084	0.13	0.28	140	-10000	0	140
p38alpha-beta/HBP1	0.053	0.058	0.24	1	-10000	0	1
CREB1	0.023	0.071	0.23	1	-0.23	2	3
RAB5/GDP	0.019	0.034	-10000	0	-0.13	24	24
EIF4E	-0.015	0.057	0.2	8	-0.2	6	14
RPS6KA4	0.034	0.039	0.22	1	-10000	0	1
PLA2G4A	-0.015	0.053	0.2	4	-0.2	10	14
GDI1	0.024	0.059	0.19	2	-0.23	17	19
TP53	0.01	0.051	0.17	10	-10000	0	10
RPS6KA5	0.034	0.042	0.22	1	-0.19	1	2
ESR1	0.032	0.038	0.22	1	-10000	0	1
HBP1	0.025	0.017	-10000	0	0	164	164
MEF2C	0.031	0.049	0.22	1	-0.22	7	8
MEF2A	0.031	0.047	0.22	1	-0.21	6	7
EIF4EBP1	0.019	0.076	0.23	1	-0.34	3	4
KRT19	0.035	0.04	0.21	2	-10000	0	2
ELK4	0.031	0.037	0.17	1	-10000	0	1
ATF6	0.033	0.038	-10000	0	-10000	0	0
ATF1	0.018	0.073	0.23	1	-0.3	2	3
p38alpha-beta/MAPKAPK2	0.07	0.056	-10000	0	-10000	0	0
p38alpha-beta/MAPKAPK3	0.072	0.058	0.23	2	-0.14	2	4

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.036	0.006	-10000	0	0	12	12
CLTC	0.011	0.088	-10000	0	-0.31	29	29
calcium ion-dependent exocytosis	0.017	0.064	0.13	1	-0.21	19	20
Dynamin 2/GTP	0.026	0.011	-10000	0	-0.1	1	1
EXOC4	0	0	-10000	0	-10000	0	0
CD59	0.003	0.079	-10000	0	-0.28	29	29
CPE	-0.015	0.009	-10000	0	-0.12	1	1
CTNNB1	0.036	0.006	-10000	0	0	15	15
membrane fusion	0.02	0.063	-10000	0	-0.16	31	31
CTNND1	-0.019	0.011	0.087	1	-0.18	1	2
DNM2	0.035	0.008	-10000	0	0	27	27
mol:PI-4-5-P2	0.011	0.065	0.15	7	-0.22	19	26
TSHR	-0.016	0.009	0.092	1	-0.12	1	2
INS	0.01	0.086	-10000	0	-0.44	16	16
BIN1	0.031	0.013	-10000	0	0	76	76
mol:Choline	0.02	0.063	-10000	0	-0.16	31	31
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	-0.009	0.005	-10000	0	-0.11	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.035	0.009	-10000	0	0	29	29
mol:Ca2+	0.026	0.011	-10000	0	-0.1	1	1
JUP	0.012	0.069	-10000	0	-0.26	23	23
ASAP2/amphiphysin II	0.028	0.046	-10000	0	-0.11	48	48
ARF6/GTP	0.025	0.009	-10000	0	-0.13	1	1
CDH1	0.009	0.072	-10000	0	-0.26	26	26
clathrin-independent pinocytosis	0.025	0.009	-10000	0	-0.13	1	1
MAPK8IP3	0.036	0.004	-10000	0	0	7	7
positive regulation of endocytosis	0.025	0.009	-10000	0	-0.13	1	1
EXOC2	0.036	0.006	-10000	0	0	15	15
substrate adhesion-dependent cell spreading	0.004	0.053	-10000	0	-0.31	5	5
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.034	0.01	-10000	0	0	37	37
regulation of calcium-dependent cell-cell adhesion	-0.038	0.077	0.27	23	-10000	0	23
positive regulation of phagocytosis	-0.015	0.007	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.046	0.015	-10000	0	-0.12	1	1
ACAP1	0.021	0.061	-10000	0	-0.21	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.004	0.055	-10000	0	-0.27	14	14
clathrin heavy chain/ACAP1	0.016	0.083	0.2	8	-0.23	30	38
JIP4/KLC1	0.036	0.036	-10000	0	-0.11	26	26
EXOC1	0.033	0.011	-10000	0	0	50	50
exocyst	0.003	0.052	-10000	0	-0.31	5	5
RALA/GTP	0.013	0.029	-10000	0	-0.13	16	16
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.038	0.039	-10000	0	-0.12	26	26
receptor recycling	0.025	0.009	-10000	0	-0.13	1	1
CTNNA1	-0.02	0.011	0.087	1	-0.18	1	2
NME1	-0.009	0.005	-10000	0	-0.11	1	1
clathrin coat assembly	0.011	0.088	-10000	0	-0.3	29	29
IL2RA	0.007	0.066	-10000	0	-0.33	14	14
VAMP3	-0.015	0.007	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.031	0.082	-10000	0	-0.22	30	30
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	0	0.038	-10000	0	-0.19	14	14
PLD2	0	0.038	-10000	0	-0.19	14	14
EXOC5	0.03	0.014	-10000	0	0	87	87
PIP5K1C	0.009	0.061	-10000	0	-0.22	16	16
SDC1	0.013	0.073	-10000	0	-0.26	26	26
ARF6/GDP	0.026	0.006	-10000	0	0	29	29
EXOC7	0.036	0.005	-10000	0	0	11	11
E-cadherin/beta catenin	0.04	0.08	-10000	0	-0.28	23	23
mol:Phosphatidic acid	0.02	0.063	-10000	0	-0.16	31	31
endocytosis	-0.026	0.045	0.11	48	-10000	0	48
SCAMP2	0.035	0.008	-10000	0	0	28	28
ADRB2	0.01	0.087	0.23	1	-0.3	28	29
EXOC3	0.036	0.003	-10000	0	0	4	4
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.023	0.01	0.09	1	-0.1	1	2
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	0.004	0.084	-10000	0	-0.3	29	29
RALA	0.024	0.018	-10000	0	0	182	182
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.02	0.084	0.22	1	-0.26	28	29

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.033	0.028	-10000	0	-0.13	11	11
VEGFR1 homodimer/NRP1	-0.014	0.016	-10000	0	-10000	0	0
mol:DAG	-0.018	0.032	0.19	1	-10000	0	1
VEGFR1 homodimer/NRP1/VEGFR 121	0.008	0.017	-10000	0	-10000	0	0
CaM/Ca2+	-0.023	0.041	0.16	3	-0.2	3	6
HIF1A	0.04	0.013	-10000	0	-10000	0	0
GAB1	0.033	0.011	-10000	0	0	55	55
AKT1	-0.032	0.088	0.2	7	-0.3	27	34
PLCG1	-0.018	0.032	0.19	1	-10000	0	1
NOS3	0.007	0.067	-10000	0	-0.3	8	8
CBL	0.036	0.005	-10000	0	0	8	8
mol:NO	0.014	0.076	0.23	1	-0.3	7	8
FLT1	0.016	0.008	-10000	0	-10000	0	0
PGF	0.031	0.013	-10000	0	0	74	74
VEGFR1 homodimer/NRP2/VEGFR121	0.03	0.025	-10000	0	-0.11	11	11
CALM1	0.033	0.012	-10000	0	0	57	57
PIK3CA	0.031	0.014	-10000	0	0	82	82
eNOS/Hsp90	-0.001	0.069	-10000	0	-0.29	7	7
endothelial cell proliferation	-0.002	0.052	0.2	4	-0.25	3	7
mol:Ca2+	-0.018	0.032	0.15	3	-10000	0	3
MAPK3	-0.027	0.033	0.15	3	-10000	0	3
MAPK1	-0.027	0.033	0.15	1	-0.19	1	2
PIK3R1	0.032	0.012	-10000	0	0	63	63
PLGF homodimer	0.031	0.013	-10000	0	0	74	74
PRKACA	0.035	0.008	-10000	0	0	24	24
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.016	0.018	-10000	0	0	288	288
VEGFA homodimer	0	0	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	-0.014	0.016	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.025	0.048	0.22	1	-0.19	1	2
PI3K	0.036	0.078	-10000	0	-0.2	15	15
PRKCA	-0.023	0.031	0.17	1	-10000	0	1
PRKCB	-0.017	0.029	0.17	1	-10000	0	1
VEGFR1 homodimer/PLGF homodimer	0.03	0.029	-10000	0	-0.13	11	11
VEGFA	0	0	-10000	0	-10000	0	0
VEGFB	0.036	0.004	-10000	0	0	7	7
mol:IP3	-0.018	0.032	0.19	1	-10000	0	1
RASA1	-0.026	0.027	0.15	3	-0.2	5	8
NRP2	0.036	0.005	-10000	0	0	8	8
VEGFR1 homodimer	0.016	0.008	-10000	0	-10000	0	0
VEGFB homodimer	0.036	0.004	-10000	0	0	7	7
NCK1	0.035	0.008	-10000	0	0	27	27
eNOS/Caveolin-1	0.001	0.072	-10000	0	-0.28	16	16
PTPN11	0.036	0.005	-10000	0	0	11	11
mol:PI-3-4-5-P3	0.035	0.077	-10000	0	-0.2	15	15
mol:L-citrulline	0.014	0.076	0.23	1	-0.3	7	8
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.04	0.044	-10000	0	-0.14	10	10
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.028	0.029	-10000	0	-0.2	1	1
CD2AP	0.034	0.01	-10000	0	0	40	40
PI3K/GAB1	0.042	0.088	-10000	0	-0.2	22	22
PDPK1	-0.029	0.067	0.24	4	-0.2	13	17
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.028	0.029	-10000	0	-0.2	1	1
mol:NADP	0.014	0.076	0.23	1	-0.3	7	8
HSP90AA1	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.039	0.043	-10000	0	-0.13	10	10
VEGFR1 homodimer/NRP2	0.032	0.028	-10000	0	-0.13	11	11

×

Canonical NF-kappaB 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
FBXW11	0.033	0.021	0.078	8	-0.059	18	26
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.003	0.08	-10000	0	-0.26	14	14
ERC1	0	0	-10000	0	-10000	0	0
RIP2/NOD2	0.026	0.011	-10000	0	-0.13	2	2
NFKBIA	-0.033	0.047	0.2	1	-0.28	14	15
BIRC2	0.036	0.006	-10000	0	0	12	12
IKBKB	0.036	0.003	-10000	0	0	4	4
RIPK2	0.036	0.006	-10000	0	0	14	14
IKBKG	0.021	0.046	-10000	0	-0.25	9	9
IKK complex/A20	0.06	0.073	-10000	0	-0.26	9	9
NEMO/A20/RIP2	0.036	0.006	-10000	0	0	14	14
XPO1	0.036	0.004	-10000	0	0	5	5
NEMO/ATM	0.039	0.055	-10000	0	-0.29	7	7
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	0	10	10
Exportin 1/RanGTP	0.047	0.023	-10000	0	-0.15	6	6
IKK complex/ELKS	0.028	0.052	-10000	0	-0.25	7	7
BCL10/MALT1/TRAF6	0.063	0.035	-10000	0	-0.13	10	10
NOD2	0	0	-10000	0	-10000	0	0
NFKB1	0.033	0.02	0.078	9	-0.056	18	27
RELA	0.034	0.021	0.078	9	-0.073	15	24
MALT1	0.034	0.009	-10000	0	0	34	34
cIAP1/UbcH5C	0.05	0.028	-10000	0	-0.18	6	6
ATM	0.034	0.01	-10000	0	0	37	37
TNF/TNFR1A	0.035	0.056	-10000	0	-0.14	43	43
TRAF6	0.036	0.005	-10000	0	0	10	10
PRKCA	0.036	0.004	-10000	0	0	6	6
CHUK	0.025	0.017	-10000	0	0	165	165
UBE2D3	0.036	0.006	-10000	0	0	12	12
TNF	0.036	0.003	-10000	0	0	4	4
NF kappa B1 p50/RelA	0.065	0.06	-10000	0	-0.17	27	27
BCL10	0.035	0.007	-10000	0	0	19	19
proteasomal ubiquitin-dependent protein catabolic process	-0.03	0.055	0.2	9	-0.28	14	23
beta TrCP1/SCF ubiquitin ligase complex	0.033	0.021	0.078	8	-0.059	18	26
TNFRSF1A	0.032	0.012	-10000	0	0	65	65
IKK complex	0.04	0.061	-10000	0	-0.26	7	7
CYLD	0.036	0.006	-10000	0	0	14	14
IKK complex/PKC alpha	0.05	0.067	-10000	0	-0.26	7	7

×

Circadian rhythm 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
chromatin modification	0.03	0.15	-10000	0	-0.99	10	10
CLOCK	0.033	0.019	-10000	0	-0.067	10	10
TIMELESS/CRY2	0.024	0.16	-10000	0	-1	10	10
DEC1/BMAL1	0.033	0.057	-10000	0	-0.13	49	49
ATR	0.035	0.008	-10000	0	0	25	25
NR1D1	0.014	0.066	-10000	0	-0.38	2	2
ARNTL	0.032	0.02	-10000	0	-0.069	8	8
TIMELESS	0.001	0.16	-10000	0	-1.1	10	10
NPAS2	0.037	0.017	-10000	0	-0.067	10	10
CRY2	0.035	0.007	-10000	0	0	21	21
mol:CO	-0.01	0.027	0.13	10	-0.1	2	12
CHEK1	0.033	0.011	-10000	0	0	50	50
mol:HEME	0.01	0.027	0.1	2	-0.13	10	12
PER1	0.033	0.011	-10000	0	0	53	53
BMAL/CLOCK/NPAS2	0.056	0.076	0.23	1	-0.14	51	52
BMAL1/CLOCK	0.011	0.12	-10000	0	-0.52	17	17
S phase of mitotic cell cycle	0.03	0.15	-10000	0	-0.99	10	10
TIMELESS/CHEK1/ATR	0.03	0.16	-10000	0	-1	10	10
mol:NADPH	0.01	0.027	0.1	2	-0.13	10	12
PER1/TIMELESS	0.022	0.16	-10000	0	-1	10	10
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.036	0.006	-10000	0	0	16	16

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.004	0.083	-10000	0	-0.28	22	22
BAG4	0.036	0.005	-10000	0	0	11	11
BAD	-0.004	0.033	0.1	2	-0.14	11	13
NFKBIA	0.033	0.012	-10000	0	0	57	57
BIRC3	0.031	0.014	-10000	0	0	82	82
BAX	0.001	0.044	0.19	13	-0.14	9	22
EnzymeConsortium:3.1.4.12	0.004	0.021	0.061	2	-0.076	12	14
IKBKB	-0.005	0.082	0.2	3	-0.29	18	21
MAP2K2	-0.008	0.052	0.18	23	-0.16	6	29
MAP2K1	-0.015	0.039	0.17	5	-0.17	6	11
SMPD1	0.003	0.029	0.11	1	-0.12	15	16
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.012	0.078	-10000	0	-0.32	10	10
MAP2K4	-0.007	0.036	0.16	4	-0.15	5	9
protein ubiquitination	-0.007	0.082	-10000	0	-0.3	18	18
EnzymeConsortium:2.7.1.37	-0.014	0.046	0.17	8	-0.18	6	14
response to UV	0	0	0.002	4	-0.002	1	5
RAF1	-0.01	0.038	0.18	5	-0.15	9	14
CRADD	0.036	0.005	-10000	0	0	11	11
mol:ceramide	0.003	0.032	0.11	1	-0.12	13	14
I-kappa-B-alpha/RELA/p50/ubiquitin	0.04	0.033	-10000	0	-0.12	18	18
MADD	0.035	0.006	-10000	0	0	15	15
MAP3K1	-0.002	0.033	0.15	2	-0.14	8	10
TRADD	0.036	0.005	-10000	0	0	10	10
RELA/p50	0.036	0.004	-10000	0	0	7	7
MAPK3	-0.006	0.046	0.18	9	-0.17	5	14
MAPK1	-0.013	0.056	0.18	8	-0.2	13	21
p50/RELA/I-kappa-B-alpha	0.043	0.039	-10000	0	-0.14	18	18
FADD	0.009	0.076	-10000	0	-0.31	9	9
KSR1	-0.004	0.031	0.11	1	-0.14	8	9
MAPK8	-0.009	0.031	0.16	3	-0.15	3	6
TRAF2	0.036	0.006	-10000	0	0	16	16
response to radiation	0	0	0.002	1	-10000	0	1
CHUK	-0.009	0.077	-10000	0	-0.3	16	16
TNF R/SODD	0.035	0.055	-10000	0	-0.14	42	42
TNF	0.036	0.003	-10000	0	0	4	4
CYCS	0.016	0.052	0.15	19	-0.14	9	28
IKBKG	-0.006	0.08	-10000	0	-0.29	18	18
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.015	0.085	-10000	0	-0.3	17	17
RELA	0.036	0.004	-10000	0	0	7	7
RIPK1	0.035	0.007	-10000	0	0	20	20
AIFM1	-0.005	0.039	0.13	11	-0.14	12	23
TNF/TNF R/SODD	0.053	0.056	-10000	0	-0.13	41	41
TNFRSF1A	0.032	0.012	-10000	0	0	65	65
response to heat	0	0	0.002	1	-10000	0	1
CASP8	0.038	0.071	-10000	0	-0.57	6	6
NSMAF	0.007	0.084	0.21	5	-0.3	17	22
response to hydrogen peroxide	0	0	0.002	4	-0.002	1	5
BCL2	0.035	0.007	-10000	0	0	20	20

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.008	0.034	0.14	27	-0.18	3	30
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	-0.01	0.047	0.12	2	-0.18	9	11
AP2	0.021	0.028	-10000	0	-0.13	15	15
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.029	0.036	-10000	0	-0.12	14	14
CLTB	0.036	0.005	-10000	0	0	9	9
coatomer protein complex/ARF1/GTP/ER cargo protein	0.015	0.03	-10000	0	-0.19	9	9
CD4	0.031	0.013	-10000	0	0	74	74
CLTA	0.034	0.01	-10000	0	0	41	41
mol:GTP	-0.003	0.002	-10000	0	-0.019	6	6
ARFGAP1	-0.011	0.003	0	41	-10000	0	41
mol:PI-4-5-P2	0.008	0.019	0.1	11	-10000	0	11
ARF1/GTP	0.019	0.018	-10000	0	-0.1	8	8
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.001	0.031	-10000	0	-0.18	9	9
mol:Choline	0.008	0.019	0.11	11	-10000	0	11
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.035	0.008	-10000	0	0	24	24
DDEF1	0.006	0.018	0.1	9	-10000	0	9
ARF1/GDP	0.006	0.012	-10000	0	-0.08	5	5
AP2M1	0.034	0.01	-10000	0	0	40	40
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.012	0.017	0.067	1	-0.12	8	9
Rac/GTP	0.017	0.02	-10000	0	-0.14	5	5
ARF1/GTP/GGA3/ARF-GAP1	0.041	0.025	-10000	0	-0.11	8	8
ARFIP2	0.032	0.015	-10000	0	-0.038	13	13
COPA	0.036	0.006	-10000	0	0	14	14
RAC1	0.025	0.017	-10000	0	0	163	163
ARF1/GTP/coatomer protein complex	0.005	0.043	-10000	0	-0.18	10	10
ARF1/GTP/ARHGAP10	0.021	0.016	-10000	0	-0.12	6	6
GGA3	0.036	0.005	-10000	0	0	8	8
ARF1/GTP/Membrin	0.027	0.028	-10000	0	-0.24	4	4
AP2A1	0	0	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.006	0.034	-10000	0	-0.18	10	10
ARF1/GDP/Membrin	0.03	0.031	-10000	0	-0.27	4	4
Arfaptin 2/Rac/GDP	0.028	0.035	-10000	0	-0.12	14	14
CYTH2	-0.003	0.002	-10000	0	-0.019	6	6
ARF1/GTP/GGA3	0.044	0.021	-10000	0	-0.12	6	6
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.017	0.02	-10000	0	-0.13	5	5
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	0.004	0.058	-10000	0	-0.19	29	29
PLD2	0.008	0.019	0.11	11	-10000	0	11
ARF-GAP1/v-SNARE	-0.011	0.003	0	41	-10000	0	41
PIP5K1A	0.008	0.019	0.1	11	-10000	0	11
ARF1/GTP/Membrin/GBF1/p115	0.002	0.037	-10000	0	-0.1	10	10
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.008	0.019	0.11	11	-10000	0	11
KDEL Receptor/Ligand/ARF-GAP1	-0.011	0.003	0	41	-10000	0	41
GOSR2	0.015	0.028	-10000	0	-0.32	3	3
USO1	0.002	0.006	0.03	17	-0.031	4	21
GBF1	-0.075	0.15	-10000	0	-0.31	141	141
ARF1/GTP/Arfaptin 2	0.042	0.034	-10000	0	-0.12	17	17
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.03	0.046	-10000	0	-0.13	35	35

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	-0.054	0.018	-10000	0	-10000	0	0
KIRREL	0.038	0.01	0.075	1	-0.041	1	2
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.054	0.018	-10000	0	-10000	0	0
PLCG1	0.034	0.01	-10000	0	0	37	37
ARRB2	0.035	0.008	-10000	0	0	25	25
WASL	0.025	0.017	-10000	0	0	167	167
Nephrin/NEPH1/podocin/CD2AP	0.084	0.05	0.2	1	-0.12	17	18
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.014	0.037	-10000	0	-0.22	6	6
FYN	-0.008	0.046	0.18	24	-10000	0	24
mol:Ca2+	0.082	0.039	0.19	1	-0.13	3	4
mol:DAG	0.084	0.04	0.2	1	-0.13	3	4
NPHS2	0.039	0.008	0.075	1	-0.041	1	2
mol:IP3	0.084	0.04	0.2	1	-0.13	3	4
regulation of endocytosis	0.052	0.051	-10000	0	-0.14	4	4
Nephrin/NEPH1/podocin/Cholesterol	0.069	0.027	0.15	8	-10000	0	8
establishment of cell polarity	0.054	0.018	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2	0.095	0.059	-10000	0	-0.14	17	17
Nephrin/NEPH1/beta Arrestin2	0.055	0.052	-10000	0	-0.14	4	4
NPHS1	0.039	0.01	0.077	7	-10000	0	7
Nephrin/NEPH1/podocin	0.052	0.045	0.21	1	-0.067	51	52
TJP1	0.034	0.009	-10000	0	0	33	33
NCK1	0.035	0.008	-10000	0	0	27	27
NCK2	0.036	0.007	-10000	0	0	17	17
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.085	0.041	0.2	1	-0.13	3	4
CD2AP	0.034	0.01	-10000	0	0	40	40
Nephrin/NEPH1/podocin/GRB2	0.087	0.043	0.2	1	-0.13	7	8
GRB2	0.035	0.007	-10000	0	0	18	18
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.014	0.051	0.18	26	-10000	0	26
cytoskeleton organization	-0.01	0.036	0.17	9	-0.2	3	12
Nephrin/NEPH1	0.046	0.016	-10000	0	-10000	0	0
Nephrin/NEPH1/ZO-1	0.065	0.038	-10000	0	-0.14	9	9

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.035	0.032	-10000	0	-10000	0	0
IHH	0.052	0.012	-10000	0	-10000	0	0
SHH Np/Cholesterol/GAS1	0.014	0.028	-10000	0	-0.11	16	16
LRPAP1	0.036	0.007	-10000	0	0	17	17
dorsoventral neural tube patterning	-0.014	0.027	0.11	16	-10000	0	16
SMO/beta Arrestin2	0.09	0.063	0.26	12	-10000	0	12
SMO	0.025	0.031	0.19	1	-10000	0	1
AKT1	-0.008	0.13	-10000	0	-0.44	30	30
ARRB2	0.035	0.008	-10000	0	0	25	25
BOC	0	0	-10000	0	-10000	0	0
ADRBK1	0.036	0.005	-10000	0	0	10	10
heart looping	0.026	0.034	0.22	3	-10000	0	3
STIL	0.05	0.092	0.19	145	-10000	0	145
DHH N/PTCH2	0.027	0.003	-10000	0	-10000	0	0
DHH N/PTCH1	0.017	0.021	0.12	21	-10000	0	21
PIK3CA	0.031	0.014	-10000	0	0	82	82
DHH	0	0	-10000	0	-10000	0	0
PTHLH	0.038	0.048	-10000	0	-10000	0	0
determination of left/right symmetry	0.026	0.034	0.22	3	-10000	0	3
PIK3R1	0.032	0.012	-10000	0	0	63	63
skeletal system development	0.038	0.048	-10000	0	-10000	0	0
IHH N/Hhip	0.034	0.008	-10000	0	-10000	0	0
DHH N/Hhip	0	0	-10000	0	-10000	0	0
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.026	0.034	0.22	3	-10000	0	3
pancreas development	0	0	-10000	0	-10000	0	0
HHAT	0.035	0.007	-10000	0	0	18	18
PI3K	0.018	0.076	-10000	0	-0.16	72	72
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.031	0.014	-10000	0	0	86	86
somite specification	0.026	0.034	0.22	3	-10000	0	3
SHH Np/Cholesterol/PTCH1	0.018	0.025	0.17	1	-10000	0	1
SHH Np/Cholesterol/PTCH2	0.021	0.016	-10000	0	-10000	0	0
SHH Np/Cholesterol/Megalin	0.02	0.016	-10000	0	-10000	0	0
SHH	-0.015	0.012	0.093	1	-10000	0	1
catabolic process	0.02	0.026	0.14	22	-10000	0	22
SMO/Vitamin D3	0.022	0.037	0.19	14	-10000	0	14
SHH Np/Cholesterol/Hhip	-0.01	0.008	-10000	0	-10000	0	0
LRP2	0.036	0.006	-10000	0	0	12	12
receptor-mediated endocytosis	0.023	0.039	0.18	16	-10000	0	16
SHH Np/Cholesterol/BOC	-0.01	0.008	-10000	0	-10000	0	0
SHH Np/Cholesterol/CDO	0.021	0.016	-10000	0	-10000	0	0
mesenchymal cell differentiation	0.01	0.008	-10000	0	-10000	0	0
mol:Vitamin D3	0.075	0.087	0.2	163	-10000	0	163
IHH N/PTCH2	0.061	0.011	-10000	0	-10000	0	0
CDON	0.036	0.004	-10000	0	0	7	7
IHH N/PTCH1	0.046	0.028	0.17	21	-10000	0	21
Megalin/LRPAP1	0.049	0.029	-10000	0	-0.14	10	10
PTCH2	0.036	0.005	-10000	0	0	8	8
SHH Np/Cholesterol	0.012	0.009	-10000	0	-10000	0	0
PTCH1	0.02	0.026	0.14	22	-10000	0	22
HHIP	0	0	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	0.037	0.028	-9999	0	-0.097	20	20
MAPK9	0.008	0.001	-9999	0	0	13	13
adrenocorticotropin secretion	-0.011	0.002	0	17	-10000	0	17
GNB1/GNG2	0.02	0.026	-9999	0	-0.11	20	20
GNB1	0.035	0.007	-9999	0	0	20	20
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	0	-10000	0	0
mol:GDP	0	0	-9999	0	-10000	0	0
MAPK14	0.008	0.001	-9999	0	0	5	5
Gs family/GTP	0.023	0.004	-9999	0	-10000	0	0
EntrezGene:2778	0	0	-9999	0	-10000	0	0
vasopressin secretion	0	0	-9999	0	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	0	-10000	0	0
glutamate secretion	0.003	0	-9999	0	-10000	0	0
GNAL	0.036	0.006	-9999	0	0	13	13
GNG2	0	0	-9999	0	-10000	0	0
CRH	0.036	0.007	-9999	0	0	17	17
mol:cortisol	0	0	-9999	0	-10000	0	0
MAPK8	0.006	0.003	-9999	0	0	143	143
MAPK11	0.007	0.002	-9999	0	0	54	54

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.035	0.007	-10000	0	0	21	21
Ran/GTP/Exportin 1/HDAC4	-0.033	0.031	-10000	0	-0.16	20	20
MDM2/SUMO1	0.034	0.054	-10000	0	-0.21	6	6
HDAC4	0.035	0.009	-10000	0	0	30	30
Ran/GTP/Exportin 1/HDAC1	-0.031	0.03	-10000	0	-0.16	18	18
SUMO1	0.036	0.003	-10000	0	0	4	4
NPC/RanGAP1/SUMO1	0.005	0.035	-10000	0	-0.15	21	21
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	-0.009	0.041	-10000	0	-0.16	21	21
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	0	10	10
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.035	0.008	-10000	0	0	25	25
SUMO1/HDAC4	0.033	0.059	-10000	0	-0.24	6	6
SUMO1/HDAC1	0.036	0.056	-10000	0	-0.22	6	6
RANGAP1	0.033	0.011	-10000	0	0	46	46
MDM2/SUMO1/SUMO1	0.077	0.048	-10000	0	-0.12	17	17
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.007	0.034	-10000	0	-0.15	21	21
Ran/GTP	0.019	0.05	-10000	0	-0.15	21	21
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.034	0.01	-10000	0	0	45	45
UBE2I	0.036	0.004	-10000	0	0	6	6
Ran/GTP/Exportin 1	0.013	0.052	0.2	1	-0.27	5	6
NPC	0.017	0.021	-10000	0	-0.09	18	18
PIAS2	0.035	0.007	-10000	0	0	19	19
PIAS1	0.035	0.008	-10000	0	0	25	25
EntrezGene:9972	0	0	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	0.041	0.2	0.61	1	-0.7	17	18
PCK1	0.045	0.12	0.43	2	-0.67	2	4
HNF4A	0.052	0.17	0.69	4	-0.71	6	10
KCNJ11	0.067	0.18	0.48	4	-0.59	16	20
AKT1	0.058	0.13	0.44	1	-0.38	16	17
response to starvation	0.003	0.002	-10000	0	-10000	0	0
DLK1	0.08	0.19	0.57	3	-0.61	13	16
NKX2-1	0.03	0.11	0.28	3	-0.34	13	16
ACADM	0.05	0.18	0.53	2	-0.75	9	11
TAT	0.051	0.13	0.53	2	-0.64	5	7
CEBPB	0.033	0.015	0.12	1	-10000	0	1
CEBPA	0.031	0.018	0.094	1	-10000	0	1
TTR	0.032	0.19	0.67	3	-0.65	11	14
PKLR	0.056	0.17	0.49	4	-0.69	7	11
APOA1	0.078	0.22	0.65	5	-0.84	7	12
CPT1C	0.055	0.17	0.47	4	-0.57	13	17
ALAS1	0.031	0.24	0.43	1	-1.2	15	16
TFRC	0.021	0.3	0.53	5	-0.96	35	40
FOXF1	0.031	0.013	-10000	0	-10000	0	0
NF1	0.034	0.036	0.11	1	-0.17	15	16
HNF1A (dimer)	0.006	0.005	0.12	1	-10000	0	1
CPT1A	0.052	0.17	0.61	1	-0.69	7	8
HMGCS1	0.057	0.17	0.52	4	-0.65	8	12
NR3C1	0.047	0.02	-10000	0	-10000	0	0
CPT1B	0.053	0.17	0.49	3	-0.69	7	10
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.036	0.006	-10000	0	-10000	0	0
GCK	0.093	0.19	0.52	16	-0.59	8	24
CREB1	0.044	0.013	0.15	1	-10000	0	1
IGFBP1	0.053	0.13	-10000	0	-0.65	4	4
PDX1	0.053	0.11	0.33	4	-0.34	8	12
UCP2	0.023	0.25	0.49	5	-0.69	42	47
ALDOB	0.066	0.19	0.5	3	-0.67	10	13
AFP	0.015	0.033	0.28	2	-10000	0	2
BDH1	0.044	0.2	0.51	2	-0.68	18	20
HADH	0.067	0.18	0.48	4	-0.59	16	20
F2	0.076	0.21	0.78	2	-0.84	7	9
HNF1A	0.006	0.005	0.12	1	-10000	0	1
G6PC	0.009	0.082	0.43	1	-10000	0	1
SLC2A2	0.063	0.13	0.45	1	-0.46	2	3
INS	0.025	0.043	0.19	14	-0.097	34	48
FOXA1	0.014	0.013	0.15	2	-10000	0	2
FOXA3	0.019	0.057	0.2	5	-0.19	23	28
FOXA2	0.1	0.23	0.63	3	-0.67	16	19
ABCC8	0.067	0.19	0.52	2	-0.69	9	11
ALB	0.016	0.033	0.31	1	-10000	0	1

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.036	0.004	-9999	0	6	6
Aurora C/Aurora B/INCENP	0.063	0.022	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.005	0.064	-9999	-0.39	13	13
AURKB	0.034	0.01	-9999	0	41	41
AURKC	0.036	0.006	-9999	0	15	15

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.036	0.005	0	9	-9999	0	9
PI3K Class IB/PDE3B	0.036	0.005	-9999	0	0	9	9
PDE3B	0.036	0.005	-9999	0	0	9	9

×

LPA4-mediated signaling events

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.Total.Perturbations
ADCY4	-0.009	0.001	0	3	-9999	3
ADCY5	-0.009	0.001	0	3	-9999	3
ADCY6	-0.017	0.006	0.086	1	-9999	1
ADCY7	-0.014	0.018	0.086	15	-9999	15
ADCY1	-0.012	0.009	-10000	0	-9999	0
ADCY2	-0.017	0.007	0.086	2	-9999	2
ADCY3	-0.009	0.001	0	3	-9999	3
ADCY8	-0.006	0.032	0.086	54	-9999	54
PRKCE	-0.011	0.001	0	3	-9999	3
ADCY9	-0.017	0.009	0.086	4	-9999	4
mol:DAG	0	0	-10000	0	-9999	0
cAMP biosynthetic process	0.017	0.043	0.17	11	-9999	11

×

Visual signal transduction: Rods

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
mol:K +	0.036	0.005	-10000	0	0	10	10
GNAT1/GTP	0.026	0.004	-10000	0	-10000	0	0
Metarhodopsin II/Arrestin	0.047	0.01	-10000	0	-10000	0	0
PDE6G/GNAT1/GTP	0.048	0.009	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.036	0.006	-10000	0	0	13	13
GRK1	0	0	-10000	0	-10000	0	0
CNG Channel	0.069	0.024	-10000	0	-10000	0	0
mol:Na +	0.044	0.015	-10000	0	-10000	0	0
mol:ADP	0	0	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.046	0.015	-10000	0	-0.12	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.055	0.018	-10000	0	-10000	0	0
CNGB1	0.036	0.006	-10000	0	0	14	14
RDH5	0.035	0.007	-10000	0	0	19	19
SAG	0.036	0.005	-10000	0	0	10	10
mol:Ca2+	-0.034	0.026	0.16	8	-10000	0	8
Na + (4 Units)	0.041	0.018	-10000	0	-10000	0	0
RGS9	0.035	0.007	-10000	0	0	18	18
GNB1/GNGT1	0.031	0.038	-10000	0	-0.14	13	13
GNAT1/GDP	0.058	0.022	-10000	0	-0.1	1	1
GUCY2D	0.036	0.006	-10000	0	0	12	12
GNGT1	0.024	0.017	-10000	0	0	170	170
GUCY2F	0.037	0	-10000	0	-10000	0	0
GNB5	0.035	0.007	-10000	0	0	22	22
mol:GMP (4 units)	0.029	0.007	-10000	0	-10000	0	0
mol:11-cis-retinal	0.035	0.007	-10000	0	0	19	19
mol:cGMP	0.029	0.006	-10000	0	-10000	0	0
GNB1	0.035	0.007	-10000	0	0	20	20
Rhodopsin	0.051	0.013	-10000	0	-10000	0	0
SLC24A1	0.036	0.005	-10000	0	0	10	10
CNGA1	0.036	0.005	-10000	0	0	9	9
Metarhodopsin II	0.023	0.004	-10000	0	-10000	0	0
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.046	0.007	-10000	0	-10000	0	0
RGS9BP	0	0	-10000	0	-10000	0	0
Metarhodopsin II/Transducin	0.008	0.032	-10000	0	-0.15	14	14
GCAP Family/Ca ++	0.023	0.001	-10000	0	-10000	0	0
PDE6A/B	0.053	0.008	-10000	0	-10000	0	0
mol:Pi	0.045	0.015	-10000	0	-0.12	1	1
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.041	0.042	-10000	0	-0.11	13	13
PDE6B	0.036	0.004	-10000	0	0	5	5
PDE6A	0.036	0.004	-10000	0	0	7	7
PDE6G	0.037	0.003	-10000	0	0	3	3
RHO	0.036	0.006	-10000	0	0	13	13
PDE6	0.085	0.026	-10000	0	-0.11	1	1
GUCA1A	0	0	-10000	0	-10000	0	0
GC2/GCAP Family	0.047	0.002	-10000	0	-10000	0	0
GUCA1C	0	0	-10000	0	-10000	0	0
GUCA1B	0.037	0.002	-10000	0	0	1	1

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.048	0.008	-10000	0	-9999	0	0
EFNA5	0.036	0.004	-10000	0	0	5	5
FYN	-0.019	0.016	0.18	2	-9999	0	2
neuron projection morphogenesis	0.048	0.008	-10000	0	-9999	0	0
cell-cell signaling	0	0	-10000	0	-9999	0	0
Ephrin A5/EPHA5	0.048	0.008	-10000	0	-9999	0	0
EPHA5	0.036	0.005	-10000	0	0	10	10