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

Pathway.Name	Avg.Num.Perturbations
HIF-1-alpha transcription factor network	131
FOXM1 transcription factor network	107
Syndecan-4-mediated signaling events	88
Angiopoietin receptor Tie2-mediated signaling	88
Endothelins	82
TCGA08_rtk_signaling	75
Thromboxane A2 receptor signaling	74
HIF-2-alpha transcription factor network	74
TCGA08_p53	73
EGFR-dependent Endothelin signaling events	71

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	131	9979	76	-0.078	0.1	1000	-1000	-0.01	-1000
FOXM1 transcription factor network	107	5487	51	-0.32	0.061	1000	-1000	-0.056	-1000
Syndecan-4-mediated signaling events	88	5938	67	-0.14	0.036	1000	-1000	-0.031	-1000
Angiopoietin receptor Tie2-mediated signaling	88	7788	88	-0.29	0.053	1000	-1000	-0.048	-1000
Endothelins	82	7877	96	-0.14	0.036	1000	-1000	-0.03	-1000
TCGA08_rtk_signaling	75	1965	26	-0.024	0.093	1000	-1000	-0.006	-1000
Thromboxane A2 receptor signaling	74	7826	105	-0.069	0.044	1000	-1000	-0.023	-1000
HIF-2-alpha transcription factor network	74	3189	43	-0.074	0.047	1000	-1000	-0.053	-1000
TCGA08_p53	73	512	7	-0.001	0.034	1000	-1000	-0.011	-1000
EGFR-dependent Endothelin signaling events	71	1492	21	-0.005	0.093	1000	-1000	-0.009	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	71	2369	33	-0.075	0.068	1000	-1000	-0.01	-1000
Effects of Botulinum toxin	68	1774	26	-0.007	0.052	1000	-1000	-0.011	-1000
PDGFR-alpha signaling pathway	66	2929	44	-0.093	0.036	1000	-1000	-0.023	-1000
Syndecan-3-mediated signaling events	65	2295	35	-0.071	0.08	1000	-1000	-0.021	-1000
Wnt signaling	65	461	7	-0.006	0.037	1000	-1000	0	-1000
Arf6 signaling events	64	3986	62	-0.005	0.092	1000	-1000	-0.003	-1000
Canonical Wnt signaling pathway	64	3284	51	-0.097	0.071	1000	-1000	-0.027	-1000
S1P5 pathway	62	1069	17	-0.007	0.036	1000	-1000	-0.011	-1000
S1P4 pathway	62	1560	25	-0.012	0.043	1000	-1000	-0.008	-1000
TCGA08_retinoblastoma	61	493	8	-0.045	0.053	1000	-1000	-0.001	-1000
Ras signaling in the CD4+ TCR pathway	61	1045	17	-0.001	0.042	1000	-1000	-0.007	-1000
LPA receptor mediated events	60	6127	102	-0.13	0.039	1000	-1000	-0.037	-1000
EPO signaling pathway	57	3152	55	-0.001	0.082	1000	-1000	-0.012	-1000
Syndecan-1-mediated signaling events	55	1894	34	-0.004	0.035	1000	-1000	-0.017	-1000
Nongenotropic Androgen signaling	55	2897	52	-0.087	0.06	1000	-1000	-0.024	-1000
Syndecan-2-mediated signaling events	54	3737	69	-0.026	0.037	1000	-1000	-0.022	-1000
IL2 signaling events mediated by STAT5	52	1152	22	-0.074	0.042	1000	-1000	-0.021	-1000
Fc-epsilon receptor I signaling in mast cells	51	5040	97	-0.12	0.048	1000	-1000	-0.042	-1000
amb2 Integrin signaling	51	4239	82	-0.015	0.077	1000	-1000	-0.02	-1000
Glypican 2 network	51	206	4	0	0.007	1000	-1000	0	-1000
IL23-mediated signaling events	51	3086	60	-0.064	0.15	1000	-1000	-0.026	-1000
JNK signaling in the CD4+ TCR pathway	50	855	17	-0.14	0.063	1000	-1000	-0.017	-1000
Osteopontin-mediated events	49	1862	38	-0.071	0.05	1000	-1000	-0.015	-1000
PLK2 and PLK4 events	48	146	3	-0.011	0.035	1000	-1000	-0.015	-1000
Ephrin B reverse signaling	46	2219	48	-0.067	0.066	1000	-1000	-0.048	-1000
Signaling events mediated by VEGFR1 and VEGFR2	45	5642	125	-0.045	0.06	1000	-1000	-0.037	-1000
Presenilin action in Notch and Wnt signaling	44	2721	61	-0.079	0.08	1000	-1000	-0.041	-1000
FoxO family signaling	44	2842	64	-0.16	0.052	1000	-1000	-0.034	-1000
FAS signaling pathway (CD95)	44	2076	47	-0.16	0.048	1000	-1000	-0.028	-1000
IL2 signaling events mediated by PI3K	44	2559	58	-0.065	0.038	1000	-1000	-0.019	-1000
BCR signaling pathway	44	4383	99	-0.061	0.05	1000	-1000	-0.034	-1000
EPHB forward signaling	43	3716	85	-0.052	0.082	1000	-1000	-0.042	-1000
Regulation of nuclear SMAD2/3 signaling	42	5791	136	-0.21	0.19	1000	-1000	-0.044	-1000
Sphingosine 1-phosphate (S1P) pathway	42	1187	28	-0.012	0.036	1000	-1000	-0.014	-1000
Noncanonical Wnt signaling pathway	42	1107	26	-0.039	0.037	1000	-1000	-0.022	-1000
Arf6 downstream pathway	42	1812	43	-0.026	0.051	1000	-1000	-0.031	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	42	2858	68	-0.1	0.046	1000	-1000	-0.032	-1000
E-cadherin signaling in keratinocytes	42	1836	43	-0.042	0.064	1000	-1000	-0.014	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	41	2226	54	-0.034	0.082	1000	-1000	-0.027	-1000
Reelin signaling pathway	41	2333	56	-0.014	0.068	1000	-1000	-0.015	-1000
Paxillin-dependent events mediated by a4b1	41	1485	36	-0.057	0.059	1000	-1000	-0.046	-1000
BMP receptor signaling	40	3297	81	-0.031	0.058	1000	-1000	-0.009	-1000
Class I PI3K signaling events	40	2991	73	-0.053	0.062	1000	-1000	-0.016	-1000
IL12-mediated signaling events	39	3403	87	-0.11	0.094	1000	-1000	-0.025	-1000
Paxillin-independent events mediated by a4b1 and a4b7	39	1469	37	-0.034	0.083	1000	-1000	-0.017	-1000
IL1-mediated signaling events	39	2433	62	-0.045	0.074	1000	-1000	-0.036	-1000
IL6-mediated signaling events	39	2955	75	-0.076	0.11	1000	-1000	-0.027	-1000
S1P3 pathway	39	1645	42	-0.018	0.036	1000	-1000	-0.015	-1000
Signaling events mediated by PTP1B	38	2927	76	-0.033	0.059	1000	-1000	-0.033	-1000
Glypican 1 network	38	1850	48	-0.038	0.051	1000	-1000	-0.033	-1000
p38 MAPK signaling pathway	38	1673	44	0	0.043	1000	-1000	-0.012	-1000
ErbB2/ErbB3 signaling events	37	2430	65	-0.044	0.036	1000	-1000	-0.057	-1000
PLK1 signaling events	37	3222	85	-0.048	0.051	1000	-1000	-0.021	-1000
mTOR signaling pathway	37	2005	53	-0.034	0.046	1000	-1000	-0.028	-1000
Stabilization and expansion of the E-cadherin adherens junction	37	2768	74	-0.12	0.079	1000	-1000	-0.052	-1000
Hedgehog signaling events mediated by Gli proteins	36	2404	65	-0.015	0.057	1000	-1000	-0.017	-1000
TCR signaling in naïve CD8+ T cells	36	3349	93	-0.35	0.4	1000	-1000	-0.026	-1000
Neurotrophic factor-mediated Trk receptor signaling	36	4374	120	-0.035	0.087	1000	-1000	-0.037	-1000
Class I PI3K signaling events mediated by Akt	35	2410	68	-0.03	0.063	1000	-1000	-0.019	-1000
Regulation of p38-alpha and p38-beta	35	1932	54	-0.002	0.047	1000	-1000	-0.015	-1000
IGF1 pathway	35	2039	57	-0.046	0.066	1000	-1000	-0.03	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	34	2895	85	-0.12	0.12	1000	-1000	-0.031	-1000
Alternative NF-kappaB pathway	34	451	13	0	0.066	1000	-1000	0	-1000
IFN-gamma pathway	33	2249	68	-0.041	0.064	1000	-1000	-0.036	-1000
PDGFR-beta signaling pathway	33	3246	97	-0.055	0.068	1000	-1000	-0.041	-1000
a4b1 and a4b7 Integrin signaling	32	162	5	0.027	0.052	1000	-1000	0.033	-1000
S1P1 pathway	32	1156	36	-0.005	0.052	1000	-1000	-0.017	-1000
Plasma membrane estrogen receptor signaling	32	2816	86	-0.066	0.053	1000	-1000	-0.034	-1000
Caspase cascade in apoptosis	31	2309	74	-0.079	0.067	1000	-1000	-0.031	-1000
ErbB4 signaling events	31	2153	69	-0.071	0.062	1000	-1000	-0.019	-1000
IL4-mediated signaling events	31	2877	91	-0.32	0.067	1000	-1000	-0.068	-1000
E-cadherin signaling in the nascent adherens junction	31	2420	76	-0.043	0.09	1000	-1000	-0.035	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	31	2481	78	-0.022	0.072	1000	-1000	-0.03	-1000
Aurora A signaling	30	1812	60	-0.028	0.058	1000	-1000	-0.015	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	30	1359	45	-0.032	0.075	1000	-1000	-0.027	-1000
p75(NTR)-mediated signaling	29	3698	125	-0.022	0.087	1000	-1000	-0.041	-1000
Signaling events mediated by HDAC Class III	29	1172	40	-0.049	0.05	1000	-1000	-0.049	-1000
Signaling events regulated by Ret tyrosine kinase	29	2453	82	-0.057	0.063	1000	-1000	-0.026	-1000
Integrins in angiogenesis	29	2498	84	-0.044	0.071	1000	-1000	-0.016	-1000
Insulin Pathway	29	2217	74	-0.036	0.082	1000	-1000	-0.031	-1000
Signaling events mediated by PRL	29	1007	34	-0.034	0.047	1000	-1000	-0.023	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	28	646	23	-0.016	0.054	1000	-1000	-0.003	-1000
Visual signal transduction: Cones	28	1089	38	-0.014	0.058	1000	-1000	-0.012	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	28	2369	83	-0.034	0.068	1000	-1000	-0.013	-1000
Aurora B signaling	28	1889	67	-0.032	0.062	1000	-1000	-0.015	-1000
TRAIL signaling pathway	27	1332	48	-0.033	0.086	1000	-1000	-0.016	-1000
Signaling mediated by p38-gamma and p38-delta	27	417	15	-0.025	0.036	1000	-1000	-0.015	-1000
Retinoic acid receptors-mediated signaling	27	1590	58	-0.053	0.059	1000	-1000	-0.018	-1000
BARD1 signaling events	26	1503	57	-0.064	0.085	1000	-1000	-0.061	-1000
Glucocorticoid receptor regulatory network	25	2956	114	-0.13	0.064	1000	-1000	-0.042	-1000
Regulation of Telomerase	25	2612	102	-0.027	0.077	1000	-1000	-0.036	-1000
Circadian rhythm pathway	24	536	22	-0.01	0.056	1000	-1000	-0.018	-1000
Nectin adhesion pathway	24	1512	63	-0.01	0.084	1000	-1000	-0.032	-1000
Signaling events mediated by HDAC Class I	24	2514	104	-0.029	0.066	1000	-1000	-0.024	-1000
Arf6 trafficking events	24	1737	71	-0.038	0.046	1000	-1000	-0.035	-1000
Insulin-mediated glucose transport	22	710	32	-0.016	0.041	1000	-1000	-0.014	-1000
Ceramide signaling pathway	22	1722	76	-0.04	0.07	1000	-1000	-0.016	-1000
Calcium signaling in the CD4+ TCR pathway	22	711	31	-0.017	0.093	1000	-1000	-0.038	-1000
IL27-mediated signaling events	22	1143	51	-0.015	0.064	1000	-1000	-0.04	-1000
E-cadherin signaling events	22	110	5	0.033	0.062	1000	-1000	0.033	-1000
Coregulation of Androgen receptor activity	21	1656	76	-0.011	0.07	1000	-1000	-0.015	-1000
RXR and RAR heterodimerization with other nuclear receptor	21	1135	52	-0.043	0.1	1000	-1000	-0.015	-1000
Atypical NF-kappaB pathway	21	661	31	-0.021	0.036	1000	-1000	-0.013	-1000
Regulation of Androgen receptor activity	20	1449	70	-0.031	0.067	1000	-1000	-0.025	-1000
Signaling events mediated by HDAC Class II	19	1461	75	-0.03	0.093	1000	-1000	-0.025	-1000
Arf1 pathway	19	1050	54	-0.075	0.044	1000	-1000	-0.01	-1000
Canonical NF-kappaB pathway	18	705	39	-0.033	0.065	1000	-1000	-0.017	-1000
Cellular roles of Anthrax toxin	18	712	39	-0.069	0.036	1000	-1000	-0.012	-1000
Signaling events mediated by the Hedgehog family	17	888	52	-0.014	0.09	1000	-1000	-0.018	-1000
ceramide signaling pathway	17	859	49	-0.014	0.053	1000	-1000	-0.021	-1000
Signaling mediated by p38-alpha and p38-beta	17	781	44	-0.015	0.086	1000	-1000	-0.015	-1000
Sumoylation by RanBP2 regulates transcriptional repression	17	466	27	-0.032	0.077	1000	-1000	-0.025	-1000
VEGFR1 specific signals	17	989	56	-0.032	0.041	1000	-1000	-0.026	-1000
Nephrin/Neph1 signaling in the kidney podocyte	15	517	34	-0.054	0.096	1000	-1000	-0.038	-1000
Rapid glucocorticoid signaling	15	315	20	-0.011	0.036	1000	-1000	-0.01	-1000
FOXA2 and FOXA3 transcription factor networks	12	576	46	0	0.094	1000	-1000	-0.035	-1000
Aurora C signaling	10	75	7	0	0.063	1000	-1000	-0.004	-1000
Class IB PI3K non-lipid kinase events	9	27	3	-0.036	0.036	1000	-1000	-0.034	-1000
LPA4-mediated signaling events	8	104	12	-0.017	0.018	1000	-1000	-0.012	-1000
Visual signal transduction: Rods	8	440	52	-0.033	0.084	1000	-1000	-0.01	-1000
Ephrin A reverse signaling	2	18	7	-0.019	0.048	1000	-1000	-0.011	-1000
Total	5150	289493	7203	-6.9	8.6	131000	-131000	-3.1	-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	0.59	100	-0.74	88	188
HDAC7	-0.001	0.005	-10000	0	-0.049	3	3
HIF1A/ARNT/Cbp/p300/Src-1	-0.025	0.38	0.56	54	-0.68	75	129
SMAD4	0.033	0.014	0.079	10	-10000	0	10
ID2	0.048	0.47	0.62	105	-0.74	86	191
AP1	0.015	0.079	-10000	0	-0.17	71	71
ABCG2	0.014	0.46	0.6	100	-0.74	88	188
HIF1A	0.044	0.13	0.23	87	-0.15	64	151
TFF3	0.043	0.46	0.6	112	-0.73	85	197
GATA2	0.039	0.014	0.077	15	-0.079	2	17
AKT1	0.052	0.13	0.24	93	-0.18	42	135
response to hypoxia	0.011	0.088	0.16	85	-0.12	52	137
MCL1	0.055	0.47	0.6	118	-0.74	87	205
NDRG1	-0.001	0.45	0.58	90	-0.74	93	183
SERPINE1	-0.065	0.38	0.55	45	-0.75	83	128
FECH	0.044	0.46	0.6	110	-0.72	87	197
FURIN	0.051	0.47	0.6	116	-0.73	87	203
NCOA2	0.037	0.006	-10000	0	-10000	0	0
EP300	0.073	0.18	0.35	96	-0.3	28	124
HMOX1	-0.019	0.45	0.6	77	-0.77	87	164
BHLHE40	-0.054	0.4	0.54	75	-0.7	93	168
BHLHE41	-0.054	0.4	0.54	75	-0.7	93	168
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.07	0.18	0.35	46	-0.24	32	78
ENG	0.03	0.15	0.29	52	-0.25	17	69
JUN	0.035	0.013	-10000	0	-0.052	2	2
RORA	0.024	0.46	0.6	101	-0.74	88	189
ABCB1	-0.055	0.21	-10000	0	-0.83	29	29
TFRC	0.033	0.46	0.6	109	-0.74	88	197
CXCR4	0.016	0.46	0.6	99	-0.75	92	191
TF	-0.078	0.4	0.63	41	-0.74	90	131
CITED2	0.014	0.45	0.59	96	-0.74	88	184
HIF1A/ARNT	-0.073	0.44	0.64	33	-0.85	79	112
LDHA	-0.066	0.28	-10000	0	-0.96	40	40
ETS1	0.059	0.47	0.6	122	-0.73	87	209
PGK1	0.048	0.48	0.6	118	-0.75	87	205
NOS2	-0.054	0.4	0.54	75	-0.7	93	168
ITGB2	0.006	0.46	0.59	97	-0.76	88	185
ALDOA	0.055	0.47	0.6	121	-0.73	89	210
Cbp/p300/CITED2	-0.021	0.45	0.58	81	-0.78	86	167
FOS	0.026	0.018	-10000	0	-0.043	1	1
HK2	0.058	0.48	0.6	123	-0.73	89	212
SP1	0.033	0.059	0.11	40	-0.15	40	80
GCK	0.1	0.24	0.55	59	-0.51	7	66
HK1	0.002	0.44	0.63	77	-0.74	86	163
NPM1	0.053	0.47	0.62	105	-0.74	86	191
EGLN1	0.05	0.47	0.62	102	-0.74	86	188
CREB1	0.032	0.034	-10000	0	-0.1	30	30
PGM1	0.052	0.47	0.6	120	-0.74	87	207
SMAD3	0.037	0.008	0.079	10	-10000	0	10
EDN1	0.057	0.21	0.51	16	-0.61	12	28
IGFBP1	-0.01	0.41	0.63	58	-0.74	76	134
VEGFA	-0.016	0.34	0.47	83	-0.56	84	167
HIF1A/JAB1	0.045	0.1	0.2	57	-0.17	21	78
CP	-0.033	0.44	0.58	76	-0.75	93	169
CXCL12	-0.033	0.41	0.6	52	-0.73	86	138
COPS5	0.036	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4	0.039	0.052	0.14	5	-0.14	35	40
BNIP3	-0.005	0.44	0.61	88	-0.73	89	177
EGLN3	0.006	0.45	0.59	90	-0.74	86	176
CA9	-0.015	0.42	0.58	74	-0.74	84	158
TERT	0.051	0.47	0.6	122	-0.73	87	209
ENO1	0.049	0.47	0.6	121	-0.74	86	207
PFKL	0.055	0.47	0.6	120	-0.74	85	205
NCOA1	0.033	0.011	-10000	0	-10000	0	0
ADM	-0.018	0.45	0.6	81	-0.74	95	176
ARNT	0.047	0.13	0.23	91	-0.14	74	165
HNF4A	0.038	0.01	0.084	6	-10000	0	6
ADFP	-0.029	0.44	0.61	61	-0.75	90	151
SLC2A1	0.015	0.37	0.53	76	-0.59	82	158
LEP	0.009	0.42	0.62	73	-0.73	78	151
HIF1A/ARNT/Cbp/p300	-0.036	0.38	0.56	53	-0.69	77	130
EPO	0.021	0.31	0.55	51	-0.58	42	93
CREBBP	0.078	0.18	0.35	99	-0.27	27	126
HIF1A/ARNT/Cbp/p300/HDAC7	-0.041	0.37	0.53	52	-0.67	78	130
PFKFB3	0.009	0.45	0.61	93	-0.75	84	177
NT5E	-0.026	0.44	0.62	65	-0.73	94	159

×

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	-0.087	0.66	0.99	34	-1.2	96	130
PLK1	0.061	0.16	0.7	11	-0.88	4	15
BIRC5	-0.062	0.44	0.67	14	-1.2	57	71
HSPA1B	-0.088	0.65	0.92	40	-1.2	101	141
MAP2K1	0.045	0.1	0.24	59	-10000	0	59
BRCA2	-0.086	0.66	1	33	-1.2	95	128
FOXM1	-0.23	0.97	1.1	34	-1.9	101	135
XRCC1	-0.084	0.66	1	34	-1.2	94	128
FOXM1B/p19	-0.32	0.57	-10000	0	-1.4	99	99
Cyclin D1/CDK4	-0.11	0.59	0.85	30	-1.1	102	132
CDC2	-0.11	0.73	1.1	36	-1.3	102	138
TGFA	-0.071	0.58	0.85	41	-1	100	141
SKP2	-0.089	0.66	0.99	34	-1.2	96	130
CCNE1	0.024	0.037	0.1	22	-0.034	114	136
CKS1B	-0.097	0.68	1	34	-1.2	102	136
RB1	-0.073	0.37	0.48	17	-1	47	64
FOXM1C/SP1	-0.17	0.76	0.89	28	-1.5	103	131
AURKB	0.061	0.15	0.66	14	-0.97	2	16
CENPF	-0.11	0.71	1.1	36	-1.2	111	147
CDK4	0.025	0.052	0.15	31	-10000	0	31
MYC	-0.1	0.56	0.8	36	-1	107	143
CHEK2	0.037	0.092	0.23	51	-10000	0	51
ONECUT1	-0.089	0.63	0.89	40	-1.2	101	141
CDKN2A	0.003	0.018	-10000	0	-0.13	4	4
LAMA4	-0.092	0.66	0.97	35	-1.2	96	131
FOXM1B/HNF6	-0.16	0.77	0.94	35	-1.5	101	136
FOS	-0.15	0.7	0.98	33	-1.2	124	157
SP1	0.034	0.019	0.072	3	-0.045	24	27
CDC25B	-0.093	0.67	0.97	36	-1.2	99	135
response to radiation	0.023	0.067	0.14	79	-10000	0	79
CENPB	-0.085	0.67	0.96	39	-1.2	97	136
CENPA	-0.09	0.67	1	34	-1.2	95	129
NEK2	-0.079	0.67	1.1	34	-1.2	100	134
HIST1H2BA	-0.088	0.65	0.92	40	-1.2	101	141
CCNA2	0.022	0.031	0.096	4	-0.034	79	83
EP300	0.033	0.011	-10000	0	0	49	49
CCNB1/CDK1	-0.19	0.84	1.1	29	-1.6	109	138
CCNB2	-0.11	0.69	1	37	-1.3	104	141
CCNB1	-0.12	0.74	1.1	37	-1.4	106	143
ETV5	-0.12	0.69	0.98	34	-1.2	118	152
ESR1	-0.09	0.65	0.98	33	-1.2	95	128
CCND1	-0.098	0.62	0.89	39	-1.1	102	141
GSK3A	0.037	0.084	0.2	55	-10000	0	55
Cyclin A-E1/CDK1-2	0.047	0.1	0.25	24	-0.16	42	66
CDK2	0.024	0.037	0.1	16	-0.034	120	136
G2/M transition of mitotic cell cycle	0.027	0.081	0.18	77	-10000	0	77
FOXM1B/Cbp/p300	-0.16	0.68	0.79	19	-1.4	101	120
GAS1	-0.092	0.67	1	36	-1.2	98	134
MMP2	-0.11	0.7	1	36	-1.2	111	147
RB1/FOXM1C	-0.14	0.61	0.84	25	-1.2	100	125
CREBBP	0.036	0.005	-10000	0	-10000	0	0

×

Syndecan-4-mediated signaling events

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
PTK2	-0.031	0.16	-10000	0	-0.48	38	38
Syndecan-4/Syndesmos	-0.14	0.28	-10000	0	-0.48	149	149
positive regulation of JNK cascade	-0.13	0.26	-10000	0	-0.49	124	124
Syndecan-4/ADAM12	-0.13	0.29	-10000	0	-0.52	125	125
CCL5	0.033	0.011	-10000	0	0	53	53
Rac1/GDP	0.017	0.019	-10000	0	-0.13	5	5
DNM2	0.035	0.009	-10000	0	0	29	29
ITGA5	0.033	0.011	-10000	0	0	56	56
SDCBP	0.035	0.007	-10000	0	0	21	21
PLG	0.03	0.021	-10000	0	-0.044	26	26
ADAM12	0.024	0.017	-10000	0	0	168	168
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	-0.025	0.022	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.14	0.28	-10000	0	-0.48	149	149
Syndecan-4/CXCL12/CXCR4	-0.14	0.28	-10000	0	-0.53	122	122
Syndecan-4/Laminin alpha3	-0.13	0.29	-10000	0	-0.49	143	143
MDK	0.03	0.014	-10000	0	0	92	92
Syndecan-4/FZD7	-0.14	0.3	-10000	0	-0.5	152	152
Syndecan-4/Midkine	-0.13	0.3	-10000	0	-0.49	154	154
FZD7	0.026	0.016	-10000	0	0	143	143
Syndecan-4/FGFR1/FGF	-0.098	0.28	-10000	0	-0.47	136	136
THBS1	0.03	0.014	-10000	0	0	97	97
integrin-mediated signaling pathway	-0.13	0.28	-10000	0	-0.45	171	171
positive regulation of MAPKKK cascade	-0.13	0.26	-10000	0	-0.49	124	124
Syndecan-4/TACI	-0.12	0.3	-10000	0	-0.48	149	149
CXCR4	0.029	0.015	-10000	0	0	103	103
cell adhesion	-0.009	0.054	0.2	3	-0.25	17	20
Syndecan-4/Dynamin	-0.12	0.29	-10000	0	-0.48	146	146
Syndecan-4/TSP1	-0.13	0.28	-10000	0	-0.5	137	137
Syndecan-4/GIPC	-0.12	0.29	-10000	0	-0.48	146	146
Syndecan-4/RANTES	-0.13	0.29	-10000	0	-0.49	144	144
ITGB1	0.027	0.016	-10000	0	0	138	138
LAMA1	0	0	-10000	0	-10000	0	0
LAMA3	0.033	0.011	-10000	0	0	48	48
RAC1	0.024	0.017	-10000	0	0	173	173
PRKCA	0.001	0.11	0.98	6	-10000	0	6
Syndecan-4/alpha-Actinin	-0.14	0.3	-10000	0	-0.5	151	151
TFPI	0.029	0.015	-10000	0	0	103	103
F2	0.01	0.041	-10000	0	-0.045	168	168
alpha5/beta1 Integrin	0.029	0.042	-10000	0	-0.14	20	20
positive regulation of cell adhesion	-0.13	0.27	-10000	0	-0.45	162	162
ACTN1	0.028	0.016	-10000	0	0	119	119
TNC	0.028	0.016	-10000	0	0	122	122
Syndecan-4/CXCL12	-0.14	0.28	-10000	0	-0.53	121	121
FGF6	0.035	0.008	-10000	0	0	27	27
RHOA	0.035	0.007	-10000	0	0	18	18
CXCL12	0.022	0.018	-10000	0	0	202	202
TNFRSF13B	0.036	0.005	-10000	0	0	8	8
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	-0.48	149	149
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.03	0.021	-10000	0	-0.045	27	27
cell migration	-0.011	0.016	-10000	0	-10000	0	0
PRKCD	0.031	0.021	-10000	0	-0.044	24	24
vasculogenesis	-0.13	0.27	-10000	0	-0.45	154	154
SDC4	-0.14	0.3	-10000	0	-0.49	167	167
Syndecan-4/Tenascin C	-0.14	0.3	-10000	0	-0.5	153	153
Syndecan-4/PI-4-5-P2/PKC alpha	-0.02	0.018	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.13	0.3	-10000	0	-0.49	146	146
MMP9	0.012	0.024	-10000	0	-0.042	38	38
Rac1/GTP	-0.009	0.055	0.2	3	-0.26	17	20
cytoskeleton organization	-0.13	0.27	-10000	0	-0.46	149	149
GIPC1	0.035	0.008	-10000	0	0	24	24
Syndecan-4/TFPI	-0.13	0.29	-10000	0	-0.5	145	145

×

Angiopoietin receptor Tie2-mediated signaling

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	-0.23	0.41	-10000	0	-0.82	142	142
NCK1/PAK1/Dok-R	-0.12	0.17	-10000	0	-0.38	130	130
NCK1/Dok-R	-0.14	0.35	-10000	0	-0.86	96	96
PIK3CA	0.031	0.013	-10000	0	0	80	80
mol:beta2-estradiol	0.032	0.098	0.23	96	-10000	0	96
RELA	0.036	0.005	-10000	0	0	9	9
SHC1	0.032	0.011	-10000	0	0	52	52
Rac/GDP	0.017	0.019	-10000	0	-0.13	5	5
F2	0.053	0.11	0.28	87	-0.09	64	151
TNIP2	0.036	0.006	-10000	0	0	13	13
NF kappa B/RelA	-0.12	0.36	-10000	0	-0.83	96	96
FN1	0.035	0.009	-10000	0	0	29	29
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	-0.15	0.33	-10000	0	-0.82	96	96
GRB7	0.036	0.006	-10000	0	0	14	14
PAK1	0.036	0.006	-10000	0	0	15	15
Tie2/Ang1/alpha5/beta1 Integrin	-0.13	0.36	-10000	0	-0.86	96	96
CDKN1A	-0.19	0.35	-10000	0	-0.66	164	164
ITGA5	0.033	0.011	-10000	0	0	56	56
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	0.37	3	-0.58	143	146
PLG	-0.15	0.36	-10000	0	-0.89	96	96
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.17	0.37	-10000	0	-0.75	123	123
GRB2	0.035	0.007	-10000	0	0	17	17
PIK3R1	0.032	0.012	-10000	0	0	63	63
ANGPT2	-0.22	0.45	-10000	0	-1	107	107
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	162	162
ANGPT4	0.023	0.028	-10000	0	-0.03	107	107
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	0.029	0.042	-10000	0	-0.14	20	20
FGF2	0.035	0.016	-10000	0	-0.012	43	43
STAT5A (dimer)	-0.24	0.44	-10000	0	-0.82	170	170
mol:L-citrulline	-0.12	0.32	0.37	3	-0.58	143	146
AGTR1	0.022	0.034	-10000	0	-0.048	90	90
MAPK14	-0.16	0.37	-10000	0	-0.9	96	96
Tie2/SHP2	-0.079	0.24	-10000	0	-0.85	32	32
TEK	-0.087	0.25	-10000	0	-0.96	30	30
RPS6KB1	-0.2	0.37	-10000	0	-0.77	136	136
Angiotensin II/AT1	0.015	0.036	0.076	7	-0.055	90	97
Tie2/Ang1/GRB2	-0.14	0.38	-10000	0	-0.91	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	-0.16	0.36	-10000	0	-0.88	96	96
PI3K	-0.24	0.44	-10000	0	-0.9	136	136
FES	-0.16	0.38	-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	135	135
Tie2/Ang2	-0.29	0.5	-10000	0	-0.98	160	160
Tie2/Ang1	-0.15	0.38	-10000	0	-0.93	96	96
FOXO1	-0.22	0.39	-10000	0	-0.75	166	166
ELF1	0.028	0.036	0.11	4	-0.046	81	85
ELF2	-0.14	0.36	-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	162	162
DOK2	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.17	0.32	0.39	3	-0.59	168	171
ETS1	-0.002	0.12	0.12	2	-0.25	93	95
PXN	-0.17	0.31	0.36	1	-0.65	134	135
ITGB1	0.027	0.016	-10000	0	0	138	138
NOS3	-0.15	0.35	0.4	1	-0.67	136	137
RAC1	0.024	0.017	-10000	0	0	173	173
TNF	-0.004	0.12	-10000	0	-0.25	92	92
MAPKKK cascade	-0.15	0.35	-10000	0	-0.86	96	96
RASA1	0.034	0.009	-10000	0	0	32	32
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	0.35	5	-0.52	143	148
mol:Phosphatidic acid	-0.15	0.35	-10000	0	-0.86	96	96
mol:Angiotensin II	-0.004	0.013	-10000	0	-0.032	73	73
mol:NADP	-0.12	0.32	0.37	3	-0.58	143	146
Rac1/GTP	-0.18	0.34	-10000	0	-0.7	132	132
MMP2	-0.15	0.37	-10000	0	-0.9	96	96

×

Endothelins

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
AKT1	-0.02	0.14	0.21	76	-0.26	85	161
PTK2B	0.036	0.006	-10000	0	0	16	16
mol:Ca2+	-0.1	0.25	0.38	3	-0.52	84	87
EDN1	0.005	0.092	0.15	2	-0.16	101	103
EDN3	0.033	0.011	-10000	0	0	52	52
EDN2	0.036	0.006	-10000	0	0	12	12
HRAS/GDP	-0.016	0.17	0.31	17	-0.37	57	74
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0	0.12	0.2	17	-0.25	55	72
ADCY4	-0.035	0.097	0.14	37	-0.2	96	133
ADCY5	-0.035	0.097	0.14	37	-0.2	96	133
ADCY6	-0.007	0.13	0.19	87	-0.23	64	151
ADCY7	-0.014	0.13	0.2	49	-0.24	66	115
ADCY1	-0.002	0.11	0.2	39	-0.25	42	81
ADCY2	-0.007	0.13	0.19	85	-0.24	65	150
ADCY3	-0.035	0.097	0.14	37	-0.2	96	133
ADCY8	-0.011	0.12	0.2	55	-0.23	57	112
ADCY9	-0.009	0.13	0.2	61	-0.23	66	127
arachidonic acid secretion	-0.08	0.26	0.31	28	-0.52	99	127
ETB receptor/Endothelin-1/Gq/GTP	-0.007	0.11	0.19	10	-0.25	47	57
GNAO1	0.03	0.014	-10000	0	0	87	87
HRAS	0.034	0.009	-10000	0	0	32	32
ETA receptor/Endothelin-1/G12/GTP	0.004	0.12	-10000	0	-0.23	71	71
ETA receptor/Endothelin-1/Gs/GTP	0.005	0.12	-10000	0	-0.21	102	102
mol:GTP	0	0.006	0.026	3	-0.025	4	7
COL3A1	-0.074	0.15	0.19	8	-0.36	100	108
EDNRB	0.023	0.045	0.096	62	-0.082	48	110
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.017	0.14	0.21	75	-0.28	63	138
CYSLTR1	-0.034	0.12	0.19	41	-0.24	93	134
SLC9A1	-0.014	0.086	0.13	5	-0.18	67	72
mol:GDP	-0.024	0.17	0.29	21	-0.38	55	76
SLC9A3	-0.12	0.29	-10000	0	-0.66	81	81
RAF1	-0.036	0.2	0.31	24	-0.41	82	106
JUN	-0.14	0.33	0.5	1	-0.71	87	88
JAK2	-0.021	0.14	0.21	66	-0.26	85	151
mol:IP3	-0.004	0.12	0.22	16	-0.29	38	54
ETA receptor/Endothelin-1	-0.02	0.15	-10000	0	-0.28	107	107
PLCB1	0.033	0.013	-10000	0	-0.008	38	38
PLCB2	0.028	0.023	-10000	0	-0.022	80	80
ETA receptor/Endothelin-3	0.008	0.087	-10000	0	-0.14	103	103
FOS	-0.094	0.35	0.41	16	-0.84	82	98
Gai/GDP	-0.068	0.27	-10000	0	-0.73	66	66
CRK	0.035	0.008	-10000	0	0	23	23
mol:Ca ++	-0.02	0.17	0.25	54	-0.34	75	129
BCAR1	0	0	-10000	0	-10000	0	0
PRKCB1	-0.004	0.12	0.23	25	-0.3	42	67
GNAQ	0.027	0.026	-10000	0	-0.034	70	70
GNAZ	0.031	0.013	-10000	0	0	81	81
GNAL	0.036	0.006	-10000	0	0	13	13
Gs family/GDP	-0.014	0.16	0.29	18	-0.35	55	73
ETA receptor/Endothelin-1/Gq/GTP	-0.006	0.12	0.22	9	-0.28	54	63
MAPK14	-0.014	0.099	0.17	10	-0.25	45	55
TRPC6	-0.1	0.26	0.4	1	-0.55	82	83
GNAI2	0.034	0.01	-10000	0	0	43	43
GNAI3	0.036	0.006	-10000	0	0	15	15
GNAI1	0.018	0.018	-10000	0	0	263	263
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.004	0.1	0.18	15	-0.24	46	61
ETB receptor/Endothelin-2	0.017	0.071	-10000	0	-0.11	89	89
ETB receptor/Endothelin-3	0.016	0.069	-10000	0	-0.11	84	84
ETB receptor/Endothelin-1	0	0.1	0.18	9	-0.17	96	105
MAPK3	-0.077	0.32	0.39	18	-0.73	82	100
MAPK1	-0.091	0.34	0.39	18	-0.79	82	100
Rac1/GDP	-0.012	0.15	0.31	15	-0.38	39	54
cAMP biosynthetic process	0.02	0.12	0.22	58	-0.21	47	105
MAPK8	-0.14	0.31	0.36	1	-0.59	133	134
SRC	0.036	0.006	-10000	0	0	14	14
ETB receptor/Endothelin-1/Gi/GTP	-0.029	0.14	0.15	9	-0.34	59	68
p130Cas/CRK/Src/PYK2	-0.024	0.18	0.35	13	-0.47	43	56
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.015	0.15	0.3	14	-0.38	43	57
COL1A2	-0.052	0.17	-10000	0	-0.48	59	59
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.006	0.091	-10000	0	-0.14	114	114
mol:DAG	-0.004	0.12	0.22	16	-0.29	38	54
MAP2K2	-0.052	0.26	0.34	36	-0.56	81	117
MAP2K1	-0.064	0.26	0.34	20	-0.58	84	104
EDNRA	-0.008	0.1	0.16	1	-0.2	99	100
positive regulation of muscle contraction	0.033	0.15	0.22	148	-0.26	45	193
Gq family/GDP	0.002	0.16	0.3	6	-0.35	54	60
HRAS/GTP	-0.016	0.16	0.28	24	-0.36	56	80
PRKCH	-0.009	0.12	0.25	16	-0.3	39	55
RAC1	0.024	0.017	-10000	0	0	173	173
PRKCA	-0.012	0.12	0.23	15	-0.3	42	57
PRKCB	-0.008	0.12	0.22	17	-0.28	45	62
PRKCE	-0.013	0.12	0.22	17	-0.3	43	60
PRKCD	-0.007	0.12	0.25	24	-0.29	42	66
PRKCG	-0.014	0.12	0.22	16	-0.3	46	62
regulation of vascular smooth muscle contraction	-0.12	0.41	0.45	11	-1	82	93
PRKCQ	-0.003	0.11	0.25	19	-0.3	32	51
PLA2G4A	-0.09	0.28	0.32	25	-0.56	100	125
GNA14	0.027	0.026	-10000	0	-0.034	70	70
GNA15	0.03	0.019	-10000	0	-0.034	25	25
GNA12	0.023	0.018	-10000	0	0	193	193
GNA11	0.031	0.017	-10000	0	-0.035	16	16
Rac1/GTP	0.006	0.11	-10000	0	-0.22	68	68
MMP1	0.019	0.074	0.22	10	-10000	0	10

×

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	167	167
HRAS	0.034	0.009	-10000	0	0	32	32
EGFR	0.009	0.016	-10000	0	0	381	381
AKT	0.09	0.12	0.24	130	-0.18	10	140
FOXO3	0	0	-10000	0	-10000	0	0
AKT1	0.033	0.011	-10000	0	0	53	53
FOXO1	0	0	-10000	0	-10000	0	0
AKT3	0.035	0.008	-10000	0	0	23	23
FOXO4	0	0	-10000	0	-10000	0	0
MET	0.023	0.018	-10000	0	0	191	191
PIK3CA	0.031	0.013	-10000	0	0	80	80
PIK3CB	0.035	0.007	-10000	0	0	18	18
NRAS	0.032	0.012	-10000	0	0	63	63
PIK3CG	0.025	0.017	-10000	0	0	163	163
PIK3R3	0.036	0.006	-10000	0	0	15	15
PIK3R2	0.035	0.008	-10000	0	0	23	23
NF1	0.036	0.003	-10000	0	0	4	4
RAS	-0.003	0.057	0.14	3	-0.13	50	53
ERBB2	0.036	0.004	-10000	0	0	5	5
proliferation/survival/translation	-0.024	0.051	0.22	4	-0.19	15	19
PI3K	0.041	0.092	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	35	35
FOXO	0.093	0.091	0.2	170	-10000	0	170
AKT2	0.035	0.008	-10000	0	0	28	28
PTEN	0.026	0.017	-10000	0	0	148	148

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.035	0.008	-10000	0	0	23	23
GNB1/GNG2	-0.046	0.078	-10000	0	-0.17	131	131
AKT1	-0.003	0.16	0.27	37	-0.31	35	72
EGF	0.035	0.008	-10000	0	0	25	25
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.015	0.07	0.26	22	-0.16	4	26
mol:Ca2+	-0.001	0.19	0.34	28	-0.27	125	153
LYN	-0.015	0.07	0.26	21	-0.16	7	28
RhoA/GTP	0.002	0.084	0.15	29	-0.13	87	116
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.017	0.21	0.36	30	-0.32	126	156
GNG2	0	0	-10000	0	-10000	0	0
ARRB2	0.035	0.008	-10000	0	0	26	26
TP alpha/Gq family/GDP/G beta5/gamma2	0.001	0.078	-10000	0	-0.24	35	35
G beta5/gamma2	-0.054	0.1	-10000	0	-0.22	130	130
PRKCH	-0.016	0.21	0.36	27	-0.32	127	154
DNM1	0.035	0.008	-10000	0	0	26	26
TXA2/TP beta/beta Arrestin3	0.014	0.018	-10000	0	-10000	0	0
mol:GTP	0.001	0.002	0.006	57	-0.002	5	62
PTGDR	0.035	0.008	-10000	0	0	26	26
G12 family/GTP	-0.045	0.14	-10000	0	-0.29	93	93
ADRBK1	0.036	0.006	-10000	0	0	13	13
ADRBK2	0.035	0.009	-10000	0	0	29	29
RhoA/GTP/ROCK1	0.044	0.026	-10000	0	-0.12	10	10
mol:GDP	-0.008	0.13	0.4	16	-0.27	22	38
mol:NADP	0.024	0.017	-10000	0	0	175	175
RAB11A	0.035	0.007	-10000	0	0	18	18
PRKG1	0.027	0.017	-10000	0	0	141	141
mol:IP3	-0.013	0.22	0.38	25	-0.34	125	150
cell morphogenesis	0.044	0.026	-10000	0	-0.12	10	10
PLCB2	-0.037	0.27	0.42	19	-0.45	125	144
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.013	0.072	0.24	28	-10000	0	28
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.018	0.06	0.25	14	-0.16	9	23
RHOA	0.035	0.007	-10000	0	0	18	18
PTGIR	0.034	0.009	-10000	0	0	33	33
PRKCB1	-0.017	0.22	0.37	25	-0.34	125	150
GNAQ	0.034	0.009	-10000	0	0	31	31
mol:L-citrulline	0.024	0.017	-10000	0	0	175	175
TXA2/TXA2-R family	-0.048	0.28	0.41	24	-0.47	133	157
LCK	-0.015	0.07	0.26	22	-10000	0	22
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.033	0.038	0.19	5	-0.12	1	6
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	0.03	0.041	0.19	5	-0.14	2	7
MAPK14	-0.004	0.15	0.28	37	-0.22	122	159
TGM2/GTP	-0.012	0.24	0.41	24	-0.38	92	116
MAPK11	-0.006	0.15	0.28	35	-0.22	122	157
ARHGEF1	0.011	0.12	0.22	50	-0.18	89	139
GNAI2	0.034	0.01	-10000	0	0	43	43
JNK cascade	-0.021	0.22	0.38	25	-0.35	133	158
RAB11/GDP	0.034	0.01	-10000	0	-0.009	25	25
ICAM1	-0.005	0.18	0.31	39	-0.27	126	165
cAMP biosynthetic process	-0.013	0.2	0.35	25	-0.32	94	119
Gq family/GTP/EBP50	0.013	0.051	0.24	7	-0.15	30	37
actin cytoskeleton reorganization	0.044	0.026	-10000	0	-0.12	10	10
SRC	-0.018	0.062	0.24	18	-10000	0	18
GNB5	0.035	0.008	-10000	0	0	24	24
GNB1	0.035	0.007	-10000	0	0	20	20
EGF/EGFR	-0.011	0.1	0.26	23	-0.22	43	66
VCAM1	-0.023	0.21	0.32	36	-0.33	135	171
TP beta/Gq family/GDP/G beta5/gamma2	0.001	0.078	-10000	0	-0.24	35	35
platelet activation	-0.009	0.19	0.35	32	-0.28	121	153
PGI2/IP	0.025	0.007	-10000	0	-10000	0	0
PRKACA	0.015	0.02	-10000	0	-10000	0	0
Gq family/GDP/G beta5/gamma2	0.004	0.069	-10000	0	-0.21	33	33
TXA2/TP beta/beta Arrestin2	0.004	0.047	-10000	0	-0.26	10	10
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	-0.022	0.24	0.39	25	-0.38	127	152
EGFR	0.009	0.016	-10000	0	0	381	381
TXA2/TP alpha	-0.029	0.26	0.42	19	-0.42	107	126
Gq family/GTP	0.009	0.048	0.2	12	-0.13	26	38
YES1	-0.014	0.071	0.26	23	-0.16	3	26
GNAI2/GTP	0.008	0.048	-10000	0	-0.13	3	3
PGD2/DP	0.026	0.006	-10000	0	-10000	0	0
SLC9A3R1	0.034	0.01	-10000	0	0	37	37
FYN	-0.015	0.072	0.26	21	-0.16	13	34
mol:NO	0.024	0.017	-10000	0	0	175	175
GNA15	0.033	0.012	-10000	0	0	57	57
PGK/cGMP	0.027	0.025	-10000	0	-10000	0	0
RhoA/GDP	0.034	0.01	-10000	0	-0.009	25	25
TP alpha/TGM2/GDP/G beta/gamma	0.031	0.042	0.18	4	-0.14	2	6
NOS3	0.024	0.017	-10000	0	0	175	175
RAC1	0.024	0.017	-10000	0	0	173	173
PRKCA	-0.015	0.21	0.35	28	-0.32	126	154
PRKCB	-0.016	0.21	0.35	26	-0.32	131	157
PRKCE	-0.018	0.21	0.36	26	-0.33	127	153
PRKCD	-0.019	0.22	0.36	30	-0.35	129	159
PRKCG	-0.022	0.22	0.37	25	-0.35	131	156
muscle contraction	-0.042	0.26	0.4	24	-0.44	133	157
PRKCZ	-0.016	0.2	0.35	27	-0.31	133	160
ARR3	0.037	0	-10000	0	-10000	0	0
TXA2/TP beta	0.036	0.039	0.19	4	-0.13	2	6
PRKCQ	-0.026	0.2	0.35	27	-0.32	124	151
MAPKKK cascade	-0.032	0.24	0.39	24	-0.4	125	149
SELE	-0.01	0.18	0.32	30	-0.27	134	164
TP beta/GNAI2/GDP/G beta/gamma	0.026	0.053	0.19	4	-0.16	14	18
ROCK1	0.036	0.006	-10000	0	0	15	15
GNA14	0.034	0.009	-10000	0	0	30	30
chemotaxis	-0.069	0.32	0.44	20	-0.56	135	155
GNA12	0.023	0.018	-10000	0	0	193	193
GNA13	0.035	0.007	-10000	0	0	19	19
GNA11	0.033	0.011	-10000	0	0	54	54
Rac1/GTP	0.017	0.02	-10000	0	-0.13	5	5

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.019	0.17	-10000	0	-0.67	29	29
oxygen homeostasis	0.004	0.02	0.044	66	-0.024	26	92
TCEB2	0.036	0.004	-10000	0	0	6	6
TCEB1	0.035	0.007	-10000	0	0	22	22
VHL/Elongin B/Elongin C/HIF2A	0.003	0.14	0.3	23	-0.23	53	76
EPO	-0.04	0.2	0.4	16	-0.42	59	75
FIH (dimer)	0.016	0.038	0.11	17	-0.039	66	83
APEX1	0.016	0.043	0.1	8	-0.049	48	56
SERPINE1	-0.074	0.2	0.32	7	-0.45	83	90
FLT1	-0.012	0.16	-10000	0	-0.67	23	23
ADORA2A	-0.037	0.24	0.44	35	-0.41	76	111
germ cell development	-0.036	0.23	0.43	33	-0.4	78	111
SLC11A2	-0.034	0.24	0.45	34	-0.42	77	111
BHLHE40	-0.039	0.23	0.43	32	-0.42	78	110
HIF1AN	0.016	0.038	0.11	17	-0.039	66	83
HIF2A/ARNT/SIRT1	-0.016	0.16	0.35	25	-0.29	61	86
ETS1	0.047	0.032	0.12	43	-0.11	11	54
CITED2	-0.058	0.26	-10000	0	-0.81	50	50
KDR	-0.001	0.16	-10000	0	-0.83	16	16
PGK1	-0.039	0.25	0.45	34	-0.44	84	118
SIRT1	0.024	0.017	-10000	0	0	171	171
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	-0.028	0.27	0.48	12	-0.47	78	90
EPAS1	0	0.13	0.3	35	-0.22	63	98
SP1	0.041	0.011	0.11	8	-10000	0	8
ABCG2	-0.045	0.26	0.45	34	-0.44	92	126
EFNA1	-0.04	0.24	0.43	30	-0.43	80	110
FXN	-0.039	0.23	0.43	35	-0.41	78	113
POU5F1	-0.039	0.23	0.43	32	-0.42	78	110
neuron apoptosis	0.027	0.26	0.46	78	-0.46	13	91
EP300	0.033	0.011	-10000	0	0	49	49
EGLN3	0.019	0.039	0.11	15	-0.039	66	81
EGLN2	0.022	0.041	0.11	20	-0.038	69	89
EGLN1	0.023	0.041	0.11	20	-0.037	94	114
VHL/Elongin B/Elongin C	0.045	0.023	-10000	0	-0.12	9	9
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.016	0.043	0.11	7	-0.049	47	54
SLC2A1	-0.051	0.23	0.43	27	-0.43	81	108
TWIST1	-0.064	0.21	0.41	15	-0.43	86	101
ELK1	0.038	0.035	0.11	29	-0.095	25	54
HIF2A/ARNT/Cbp/p300	0.001	0.19	0.38	31	-0.3	62	93
VEGFA	-0.039	0.23	0.43	32	-0.42	78	110
CREBBP	0.036	0.005	-10000	0	0	8	8

×

TCGA08_p53

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
CDKN2A	-0.001	0.004	0	444	-10000	0	444
TP53	0.004	0.034	-10000	0	-0.22	9	9
Senescence	0.004	0.034	-10000	0	-0.22	9	9
Apoptosis	0.004	0.034	-10000	0	-0.22	9	9
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0	0.023	0.3	3	-10000	0	3
MDM4	0.034	0.01	-10000	0	0	38	38

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.034	0.009	-10000	0	0	32	32
EGFR	0.009	0.016	-10000	0	0	381	381
EGF/EGFR	0.001	0.052	-10000	0	-0.11	64	64
EGF/EGFR dimer/SHC/GRB2/SOS1	0.006	0.057	-10000	0	-0.11	61	61
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	0.028	0.016	-10000	0	0	122	122
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	0.055	-10000	0	-0.12	61	61
mol:GDP	0.004	0.055	-10000	0	-0.11	61	61
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0.033	0.011	-10000	0	0	53	53
GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
HRAS/GTP	-0.004	0.051	-10000	0	-0.11	68	68
SHC1	0.033	0.011	-10000	0	0	52	52
HRAS/GDP	0	0.057	-10000	0	-0.12	67	67
FRAP1	0.093	0.12	0.18	302	-0.18	4	306
EGF/EGFR dimer	-0.005	0.056	-10000	0	-0.14	64	64
SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.035	0.007	-10000	0	0	17	17
ETA receptor/Endothelin-1	0.023	0.059	-10000	0	-0.14	50	50

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	0.034	0.01	-10000	0	0	41	41
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.036	0.004	-10000	0	0	6	6
TCEB1	0.035	0.007	-10000	0	0	22	22
HIF1A/p53	-0.063	0.14	-10000	0	-0.27	140	140
HIF1A	-0.057	0.12	0.16	1	-0.28	118	119
COPS5	0.036	0.006	-10000	0	0	14	14
VHL/Elongin B/Elongin C/RBX1/CUL2	0.048	0.059	-10000	0	-0.13	22	22
FIH (dimer)	0.025	0.017	-10000	0	0	156	156
CDKN2A	0.004	0.012	-10000	0	0	444	444
ARNT/IPAS	0.05	0.015	-10000	0	-10000	0	0
HIF1AN	0.025	0.017	-10000	0	0	156	156
GNB2L1	0.036	0.002	-10000	0	0	2	2
HIF1A/ARNT	-0.061	0.14	-10000	0	-0.27	140	140
CUL2	0.026	0.017	-10000	0	0	153	153
OS9	0.031	0.013	-10000	0	0	73	73
RACK1/Elongin B/Elongin C	0.068	0.032	-10000	0	-0.13	10	10
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	-0.075	0.13	-10000	0	-0.27	142	142
PHD1-3/OS9	0.063	0.064	-10000	0	-0.14	31	31
HIF1A/RACK1/Elongin B/Elongin C	-0.043	0.15	-10000	0	-0.27	142	142
VHL	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
HIF1A/JAB1	-0.063	0.14	-10000	0	-0.27	144	144
EGLN3	0.03	0.014	-10000	0	0	91	91
EGLN2	0.034	0.009	-10000	0	0	30	30
EGLN1	0.034	0.009	-10000	0	0	33	33
TP53	0.031	0.013	-10000	0	0	73	73
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.005	0.1	-10000	0	-0.61	12	12
ARNT	0.036	0.004	-10000	0	0	5	5
ARD1A	0.036	0.003	-10000	0	0	4	4
RBX1	0.033	0.01	-10000	0	0	45	45
HIF1A/p19ARF	-0.064	0.12	-10000	0	-0.26	119	119

×

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	19	19
STXBP1	0.029	0.015	-10000	0	0	106	106
ACh/CHRNA1	0.026	0.053	0.095	40	-0.075	91	131
RAB3GAP2/RIMS1/UNC13B	0.052	0.05	-10000	0	-0.13	25	25
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	0.008	-10000	0	0	23	23
mol:ACh	0.016	0.063	0.093	145	-0.09	86	231
RAB3GAP2	0.035	0.009	-10000	0	0	29	29
STX1A/SNAP25/VAMP2	0.026	0.1	0.18	19	-0.16	76	95
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.026	0.053	0.095	40	-0.075	91	131
UNC13B	0.032	0.013	-10000	0	0	70	70
CHRNA1	0.035	0.007	-10000	0	0	18	18
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0.012	0.041	0.096	9	-0.085	40	49
SNAP25	0.002	0.003	-10000	0	0	262	262
VAMP2	0.004	0.001	-10000	0	0	48	48
SYT1	0.018	0.018	-10000	0	0	262	262
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.017	0.016	-10000	0	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.026	0.1	0.18	19	-0.16	76	95

×

PDGFR-alpha 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
PDGFRA	0.017	0.031	0.081	3	-0.056	51	54
PDGF/PDGFRA/CRKL	0.007	0.067	-10000	0	-0.14	68	68
positive regulation of JUN kinase activity	0.023	0.062	-10000	0	-0.11	69	69
CRKL	0.035	0.009	-10000	0	0	29	29
PDGF/PDGFRA/Caveolin-3	0.009	0.068	-10000	0	-0.14	68	68
AP1	-0.08	0.24	0.29	12	-0.59	77	89
mol:IP3	-0.015	0.046	0.095	25	-0.11	39	64
PLCG1	-0.015	0.046	0.095	25	-0.11	39	64
PDGF/PDGFRA/alphaV Integrin	0.004	0.075	-10000	0	-0.15	78	78
RAPGEF1	0.035	0.007	-10000	0	0	19	19
CRK	0.035	0.008	-10000	0	0	23	23
mol:Ca2+	-0.015	0.046	0.095	25	-0.11	39	64
CAV3	0.036	0.005	-10000	0	0	11	11
CAV1	0.016	0.018	-10000	0	0	290	290
SHC/Grb2/SOS1	0.028	0.064	-10000	0	-0.11	69	69
PDGF/PDGFRA/Shf	-0.005	0.054	-10000	0	-0.089	119	119
FOS	-0.093	0.22	0.42	1	-0.6	71	72
JUN	-0.026	0.056	0.2	10	-0.2	16	26
oligodendrocyte development	0.003	0.075	-10000	0	-0.15	78	78
GRB2	0.035	0.007	-10000	0	0	17	17
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:DAG	-0.015	0.046	0.095	25	-0.11	39	64
PDGF/PDGFRA	0.017	0.031	0.081	3	-0.056	51	54
actin cytoskeleton reorganization	0.007	0.065	-10000	0	-0.14	65	65
SRF	-0.016	0.021	-10000	0	-10000	0	0
SHC1	0.033	0.011	-10000	0	0	52	52
PI3K	0.007	0.09	-10000	0	-0.15	108	108
PDGF/PDGFRA/Crk/C3G	0.027	0.071	-10000	0	-0.13	75	75
JAK1	-0.007	0.029	0.083	30	-10000	0	30
ELK1/SRF	-0.02	0.083	0.14	67	-0.16	60	127
SHB	0.033	0.011	-10000	0	0	51	51
SHF	0	0	-10000	0	-10000	0	0
CSNK2A1	0.027	0.034	-10000	0	-0.032	102	102
GO:0007205	-0.027	0.068	0.1	25	-0.19	55	80
SOS1	0	0	-10000	0	-10000	0	0
Ras protein signal transduction	0.023	0.062	-10000	0	-0.11	69	69
PDGF/PDGFRA/SHB	0.007	0.065	-10000	0	-0.14	65	65
PDGF/PDGFRA/Caveolin-1	-0.016	0.077	-10000	0	-0.16	97	97
ITGAV	0.034	0.009	-10000	0	0	31	31
ELK1	-0.032	0.066	0.088	26	-0.15	94	120
PIK3CA	0.031	0.013	-10000	0	0	80	80
PDGF/PDGFRA/Crk	0.006	0.072	-10000	0	-0.15	76	76
JAK-STAT cascade	-0.007	0.029	0.082	30	-10000	0	30
cell proliferation	-0.005	0.054	-10000	0	-0.089	119	119

×

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	-0.025	0.18	-9999	-0.43	76	76
Syndecan-3/Neurocan	-0.065	0.18	-9999	-0.48	78	78
POMC	0.036	0.006	-9999	0	14	14
EGFR	0.009	0.016	-9999	0	381	381
Syndecan-3/EGFR	-0.057	0.16	-9999	-0.41	78	78
AGRP	0.036	0.005	-9999	0	9	9
NCSTN	0.035	0.008	-9999	0	28	28
PSENEN	0.035	0.008	-9999	0	28	28
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.035	0.006	-9999	0	16	16
APH1A	0.036	0.005	-9999	0	11	11
NCAN	0	0	-9999	-10000	0	0
long-term memory	-0.033	0.2	-9999	-0.49	79	79
Syndecan-3/IL8	-0.056	0.18	-9999	-0.48	78	78
PSEN1	0.033	0.011	-9999	0	46	46
Src/Cortactin	0.051	0.015	-9999	-0.14	1	1
FYN	0.03	0.014	-9999	0	90	90
limb bud formation	-0.066	0.18	-9999	-0.5	78	78
MC4R	0.035	0.007	-9999	0	20	20
SRC	0.036	0.006	-9999	0	14	14
PTN	0.021	0.018	-9999	0	209	209
FGFR/FGF/Syndecan-3	-0.067	0.19	-9999	-0.5	78	78
neuron projection morphogenesis	-0.071	0.15	-9999	-0.42	75	75
Syndecan-3/AgRP	-0.044	0.19	-9999	-0.48	79	79
Syndecan-3/AgRP/MC4R	-0.025	0.19	-9999	-0.47	79	79
Fyn/Cortactin	0.029	0.061	-9999	-0.14	53	53
SDC3	-0.068	0.19	-9999	-0.51	78	78
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.055	0.18	-9999	-0.47	78	78
IL8	0.019	0.018	-9999	0	243	243
Syndecan-3/Fyn/Cortactin	-0.034	0.21	-9999	-0.5	79	79
Syndecan-3/CASK	-0.065	0.18	-9999	-0.48	78	78
alpha-MSH/MC4R	0.051	0.014	-9999	-10000	0	0
Gamma Secretase	0.08	0.069	-9999	-0.15	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	18	18
FZD3	0.029	0.015	-9999	0	110	110
WNT5A	0.029	0.015	-9999	0	99	99
WNT11	0.036	0.006	-9999	0	14	14

×

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	-0.094	7	7
EGFR	0.009	0.016	-10000	0	0	381	381
EPHA2	0.033	0.011	-10000	0	0	54	54
USP6	0.035	0.007	-10000	0	0	18	18
IQSEC1	0.035	0.007	-10000	0	0	19	19
EGFR/EGFR/EGF/EGF	-0.005	0.056	-10000	0	-0.14	64	64
ARRB2	0.012	0.025	-10000	0	-0.2	7	7
mol:GTP	0.002	0.012	-10000	0	-0.063	3	3
ARRB1	0.036	0.005	-10000	0	0	10	10
FBXO8	0	0	-10000	0	-10000	0	0
TSHR	0.033	0.011	-10000	0	0	48	48
EGF	0.035	0.008	-10000	0	0	25	25
somatostatin receptor activity	0	0	0.001	141	0	6	147
ARAP2	0	0	0	129	0	2	131
mol:GDP	0.068	0.068	0.16	125	-0.16	4	129
mol:PI-3-4-5-P3	0	0	0	132	0	5	137
ITGA2B	0.036	0.004	-10000	0	0	5	5
ARF6	0.035	0.008	-10000	0	0	27	27
Ephrin A1/EPHA2/NCK1/GIT1	0.076	0.052	-10000	0	-0.12	24	24
ADAP1	0	0	0	59	0	1	60
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	0.083	0.087	0.19	130	-0.2	5	135
EGFR/EGFR/EGF/EGF/ARFGEP100	0.001	0.055	-10000	0	-0.12	62	62
ADRB2	0.034	0.01	-10000	0	0	42	42
receptor agonist activity	0	0	0	141	0	5	146
actin filament binding	0	0	0	138	0	6	144
SRC	0.036	0.006	-10000	0	0	14	14
ITGB3	0.036	0.003	-10000	0	0	4	4
GNAQ	0.035	0.009	-10000	0	0	31	31
EFA6/PI-4-5-P2	0.001	0.001	0.001	164	-0.001	4	168
ARF6/GDP	0.036	0.063	0.16	15	-0.2	14	29
ARF6/GDP/GULP/ACAP1	0.055	0.075	0.2	19	-0.2	3	22
alphaIIb/beta3 Integrin/paxillin/GIT1	0.092	0.012	-10000	0	-10000	0	0
ACAP1	0	0	0	60	-10000	0	60
ACAP2	0	0	0	70	0	3	73
LHCGR/beta Arrestin2	0.03	0.024	-10000	0	-0.14	7	7
EFNA1	0.033	0.011	-10000	0	0	50	50
HGF	0.024	0.017	-10000	0	0	177	177
CYTH3	0	0	0.001	147	-0.001	4	151
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	141	0	5	146
endosomal lumen acidification	0	0	0	145	0	6	151
microtubule-based process	0	0	-10000	0	0	1	1
GULP1	0.024	0.017	-10000	0	0	168	168
GNAQ/ARNO	0.026	0.008	0.04	5	0	31	36
mol:Phosphatidic acid	0	0	0	70	0	3	73
PIP3-E	0.03	0.014	-10000	0	0	89	89
MET	0.023	0.018	-10000	0	0	191	191
GNA14	0.035	0.009	-10000	0	0	30	30
GNA15	0.033	0.012	-10000	0	0	57	57
GIT1	0.036	0.003	-10000	0	0	4	4
mol:PI-4-5-P2	0	0	0.001	146	-0.001	4	150
GNA11	0.033	0.011	-10000	0	0	54	54
LHCGR	0.037	0.003	-10000	0	0	3	3
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	0.043	-10000	0	-0.09	51	51
alphaIIb/beta3 Integrin	0.054	0.006	-10000	0	-10000	0	0

×

Canonical Wnt signaling 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
HDAC1	0.033	0.045	0.12	67	-0.039	84	151
AES	0.031	0.042	0.11	63	-0.036	80	143
FBXW11	0.035	0.008	-10000	0	0	25	25
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.033	0.026	-10000	0	-10000	0	0
SMAD4	0.032	0.012	-10000	0	0	58	58
DKK2	0.034	0.009	-10000	0	0	31	31
TLE1	0.031	0.041	0.11	64	-0.036	84	148
MACF1	0.033	0.011	-10000	0	0	49	49
CTNNB1	0.045	0.11	0.26	20	-0.36	14	34
WIF1	0.028	0.015	-10000	0	0	112	112
beta catenin/RanBP3	0.071	0.16	0.42	62	-0.35	9	71
KREMEN2	0.036	0.004	-10000	0	0	7	7
DKK1	0.017	0.018	-10000	0	0	271	271
beta catenin/beta TrCP1	0.06	0.11	0.27	18	-0.36	13	31
FZD1	0.024	0.017	-10000	0	0	173	173
AXIN2	-0.024	0.093	0.12	3	-0.24	66	69
AXIN1	0.037	0.001	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	0	10	10
Axin1/APC/GSK3/beta catenin	0.015	0.16	-10000	0	-0.61	28	28
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.024	0.13	0.26	9	-0.44	18	27
Axin1/APC/GSK3	0.005	0.09	0.23	5	-0.39	16	21
Axin1/APC/GSK3/beta catenin/Macf1	0.032	0.14	0.26	12	-0.39	28	40
HNF1A	0.006	0.03	0.071	73	-0.038	3	76
CTBP1	0.031	0.041	0.11	61	-0.037	83	144
MYC	-0.097	0.4	0.74	14	-1.3	49	63
RANBP3	0.035	0.008	-10000	0	0	23	23
DKK2/LRP6/Kremen 2	0.064	0.027	-10000	0	-0.12	1	1
NKD1	0	0.001	-10000	0	-10000	0	0
TCF4	0.03	0.038	0.11	59	-0.036	68	127
TCF3	0.032	0.042	0.11	64	-0.036	83	147
WNT1/LRP6/FZD1/Axin1	0.059	0.046	-10000	0	-10000	0	0
Ran/GTP	0.026	0.016	-10000	0	-0.13	5	5
CtBP/CBP/TCF/TLE1/AES	0.035	0.19	0.46	65	-0.34	20	85
LEF1	0.033	0.044	0.11	71	-0.037	86	157
DVL1	0.01	0.098	-10000	0	-0.42	18	18
CSNK2A1	0.035	0.009	-10000	0	0	31	31
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.01	0.16	0.26	8	-0.5	30	38
DKK1/LRP6/Kremen 2	0.031	0.037	-10000	0	-10000	0	0
LRP6	0.034	0.01	-10000	0	0	40	40
CSNK1A1	0.034	0.046	0.12	68	-0.038	86	154
NLK	0.026	0.023	-10000	0	-0.032	56	56
CCND1	-0.08	0.35	0.79	3	-1.3	38	41
WNT1	0.036	0.007	-10000	0	0	16	16
GSK3A	0.035	0.009	-10000	0	0	28	28
GSK3B	0.034	0.01	-10000	0	0	40	40
FRAT1	0.025	0.017	-10000	0	0	161	161
PPP2R5D	0.023	0.044	-10000	0	-0.24	8	8
APC	0.04	0.1	0.18	161	-10000	0	161
WNT1/LRP6/FZD1	0.001	0.049	-10000	0	-0.26	11	11
CREBBP	0.033	0.043	0.11	68	-0.036	86	154

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.006	0.1	0.19	87	-10000	0	87
GNAI2	0.034	0.01	-10000	0	0	43	43
S1P/S1P5/G12	0.009	0.03	-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	0.007	0.11	-10000	0	-0.2	87	87
negative regulation of cAMP metabolic process	-0.007	0.099	-10000	0	-0.21	80	80
GNAZ	0.031	0.013	-10000	0	0	81	81
GNAI3	0.036	0.006	-10000	0	0	15	15
GNA12	0.023	0.018	-10000	0	0	193	193
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.007	0.1	-10000	0	-0.21	80	80
RhoA/GDP	0.024	0.019	-10000	0	-0.13	7	7
RHOA	0.035	0.007	-10000	0	0	18	18
GNAI1	0.018	0.018	-10000	0	0	263	263

×

S1P4 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.03	0.014	-10000	0	0	87	87
CDC42/GTP	0.007	0.1	-10000	0	-0.19	84	84
PLCG1	-0.011	0.097	0.12	5	-0.2	83	88
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.034	0.01	-10000	0	0	43	43
GNAI3	0.036	0.006	-10000	0	0	15	15
G12/G13	0.025	0.047	-10000	0	-0.14	28	28
cell migration	0.006	0.1	-10000	0	-0.19	84	84
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
MAPK3	-0.012	0.098	0.12	4	-0.2	85	89
MAPK1	-0.006	0.094	0.12	5	-0.2	77	82
S1P/S1P5/Gi	-0.007	0.1	-10000	0	-0.21	80	80
GNAI1	0.018	0.018	-10000	0	0	263	263
CDC42/GDP	0.026	0.006	-10000	0	-10000	0	0
S1P/S1P5/G12	0.009	0.03	-10000	0	-0.11	28	28
RHOA	0.043	0.1	0.19	161	-0.18	3	164
S1P/S1P4/Gi	-0.007	0.1	-10000	0	-0.21	80	80
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.031	0.013	-10000	0	0	81	81
S1P/S1P4/G12/G13	0.023	0.037	-10000	0	-0.1	28	28
GNA12	0.023	0.018	-10000	0	0	193	193
GNA13	0.035	0.007	-10000	0	0	19	19
CDC42	0.035	0.008	-10000	0	0	24	24

×

TCGA08_retinoblastoma

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
CDKN2B	0.003	0.026	-10000	0	-0.053	54	54
CDKN2C	-0.009	0.021	-10000	0	-0.035	122	122
CDKN2A	0.005	0.015	-10000	0	-0.043	1	1
CCND2	-0.001	0.018	0.11	6	-10000	0	6
RB1	-0.045	0.09	0.16	2	-0.18	139	141
CDK4	-0.001	0.02	0.13	6	-10000	0	6
CDK6	-0.001	0.02	0.13	6	-10000	0	6
G1/S progression	0.053	0.095	0.19	155	-0.16	2	157

×

Ras signaling in the CD4+ TCR 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
ERK1-2/ELK1	0.024	0.14	-10000	0	-0.33	30	30
MAP3K8	0.022	0.018	-10000	0	0	197	197
FOS	0.019	0.1	-10000	0	-0.34	16	16
PRKCA	0.029	0.025	-10000	0	-0.03	76	76
PTPN7	0.028	0.029	0.066	53	-0.037	72	125
HRAS	0.034	0.009	-10000	0	0	32	32
PRKCB	0	0.008	0.016	61	-0.013	77	138
NRAS	0.032	0.012	-10000	0	0	63	63
RAS family/GTP	0.042	0.065	-10000	0	-0.13	53	53
MAPK3	0.035	0.052	-10000	0	-0.31	3	3
MAP2K1	0.012	0.055	-10000	0	-0.22	12	12
ELK1	0.026	0.029	-10000	0	-0.04	79	79
BRAF	0.007	0.021	-10000	0	-10000	0	0
mol:GTP	0	0.002	0.002	61	-0.004	77	138
MAPK1	0.008	0.13	-10000	0	-0.44	31	31
RAF1	-0.001	0.067	-10000	0	-0.34	17	17
KRAS	0.034	0.009	-10000	0	0	35	35

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.006	0.057	-10000	0	-0.14	60	60
NF kappa B1 p50/RelA/I kappa B alpha	0.007	0.096	0.21	11	-0.2	47	58
AP1	-0.009	0.073	0.088	17	-0.14	90	107
mol:PIP3	-0.024	0.05	-10000	0	-0.13	76	76
AKT1	0.002	0.094	0.2	22	-0.25	26	48
PTK2B	-0.002	0.058	0.12	6	-0.15	57	63
RHOA	0.022	0.078	0.18	17	-0.34	11	28
PIK3CB	0.035	0.007	-10000	0	0	18	18
mol:Ca2+	-0.009	0.04	0.19	5	-0.14	19	24
MAGI3	0	0	-10000	0	-0.002	1	1
RELA	0.036	0.005	-10000	0	0	9	9
apoptosis	0.002	0.062	0.1	36	-0.16	53	89
HRAS/GDP	0.021	0.027	-10000	0	-0.13	15	15
positive regulation of microtubule depolymerization	-0.02	0.074	0.17	11	-0.19	48	59
NF kappa B1 p50/RelA	-0.021	0.066	0.078	64	-0.17	53	117
endothelial cell migration	-0.017	0.097	-10000	0	-0.3	53	53
ADCY4	-0.004	0.091	0.14	13	-0.24	41	54
ADCY5	-0.004	0.091	0.14	13	-0.24	41	54
ADCY6	0.001	0.092	0.16	15	-0.25	37	52
ADCY7	-0.002	0.096	0.15	17	-0.25	42	59
ADCY1	-0.009	0.083	0.15	9	-0.26	34	43
ADCY2	-0.001	0.094	0.16	14	-0.23	44	58
ADCY3	-0.004	0.091	0.14	13	-0.24	41	54
ADCY8	-0.002	0.091	0.15	17	-0.24	39	56
ADCY9	0	0.091	0.16	15	-0.24	39	54
GSK3B	-0.009	0.065	0.18	8	-0.16	56	64
arachidonic acid secretion	-0.016	0.11	0.15	14	-0.24	66	80
GNG2	0	0.001	0.002	2	-0.003	15	17
TRIP6	-0.016	0.085	-10000	0	-0.25	57	57
GNAO1	0.003	0.057	0.12	24	-0.16	47	71
HRAS	0.034	0.009	-10000	0	0	32	32
NFKBIA	-0.017	0.083	0.17	15	-0.2	45	60
GAB1	0.032	0.012	-10000	0	0	59	59
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.009	0.21	-10000	0	-0.8	31	31
JUN	0.034	0.01	-10000	0	0	40	40
LPA/LPA2/NHERF2	0.019	0.029	-10000	0	-0.061	53	53
TIAM1	-0.015	0.25	-10000	0	-0.98	31	31
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	-0.008	0.039	0.22	3	-0.14	19	22
PLCB3	0.006	0.035	0.2	5	-10000	0	5
FOS	0.025	0.017	-10000	0	0	158	158
positive regulation of mitosis	-0.016	0.11	0.15	14	-0.24	66	80
LPA/LPA1-2-3	-0.008	0.04	-10000	0	-0.12	53	53
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	0.066	-10000	0	-0.28	9	9
GNAZ	0.003	0.063	0.12	28	-0.17	48	76
EGFR/PI3K-beta/Gab1	-0.02	0.054	-10000	0	-0.13	77	77
positive regulation of dendritic cell cytokine production	-0.008	0.04	-10000	0	-0.12	53	53
LPA/LPA2/MAGI-3	-0.004	0.017	-10000	0	-0.052	53	53
ARHGEF1	0.039	0.12	0.2	147	-0.17	34	181
GNAI2	0.004	0.069	0.12	40	-0.17	53	93
GNAI3	0.007	0.063	0.12	39	-0.15	53	92
GNAI1	0.002	0.047	0.12	19	-0.16	29	48
LPA/LPA3	-0.006	0.021	-10000	0	-0.066	53	53
LPA/LPA2	-0.005	0.021	-10000	0	-0.065	53	53
LPA/LPA1	-0.012	0.054	-10000	0	-0.17	53	53
HB-EGF/EGFR	-0.01	0.056	-10000	0	-0.14	66	66
HBEGF	0.011	0.046	0.092	116	-10000	0	116
mol:DAG	-0.008	0.039	0.22	3	-0.14	19	22
cAMP biosynthetic process	0.003	0.11	0.18	33	-0.26	43	76
NFKB1	0.035	0.007	-10000	0	0	18	18
SRC	0.036	0.006	-10000	0	0	14	14
GNB1	0.035	0.007	-10000	0	0	20	20
LYN	-0.023	0.095	0.17	17	-0.23	62	79
GNAQ	0.008	0.026	0.056	38	-0.058	55	93
LPAR2	0	0.001	0.002	1	-0.002	7	8
LPAR3	0	0.001	-10000	0	-0.002	20	20
LPAR1	-0.009	0.033	-10000	0	-0.1	53	53
IL8	-0.13	0.2	0.32	8	-0.39	157	165
PTK2	0.014	0.057	0.12	39	-0.14	50	89
Rac1/GDP	0.017	0.019	-10000	0	-0.13	5	5
CASP3	0.002	0.062	0.1	36	-0.16	53	89
EGFR	0.009	0.016	-10000	0	0	381	381
PLCG1	0.005	0.038	0.072	8	-0.099	39	47
PLD2	0.015	0.053	0.12	38	-0.12	52	90
G12/G13	0.018	0.062	-10000	0	-0.15	45	45
PI3K-beta	-0.014	0.069	-10000	0	-0.26	23	23
cell migration	-0.002	0.073	-10000	0	-0.24	31	31
SLC9A3R2	0.036	0.005	-10000	0	0	9	9
PXN	0.009	0.067	-10000	0	-0.29	9	9
HRAS/GTP	-0.018	0.11	0.16	8	-0.25	66	74
RAC1	0.024	0.017	-10000	0	0	173	173
MMP9	0.017	0.018	-10000	0	0	267	267
PRKCE	0.036	0.003	-10000	0	0	4	4
PRKCD	-0.005	0.054	0.18	14	-0.2	3	17
Gi(beta/gamma)	-0.009	0.12	0.14	21	-0.26	60	81
mol:LPA	-0.009	0.033	-10000	0	-0.1	53	53
TRIP6/p130 Cas/FAK1/Paxillin	-0.008	0.081	-10000	0	-0.22	42	42
MAPKKK cascade	-0.016	0.11	0.15	14	-0.24	66	80
contractile ring contraction involved in cytokinesis	0.021	0.08	0.18	17	-0.34	12	29
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	0.008	0.026	0.056	37	-0.058	55	92
GNA15	0.008	0.025	0.056	33	-0.057	51	84
GNA12	0.023	0.018	-10000	0	0	193	193
GNA13	0.035	0.007	-10000	0	0	19	19
MAPT	-0.02	0.075	0.17	11	-0.18	58	69
GNA11	0.011	0.022	0.056	37	-0.057	34	71
Rac1/GTP	-0.01	0.22	-10000	0	-0.85	31	31
MMP2	-0.017	0.097	-10000	0	-0.3	53	53

×

EPO signaling 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
BCL2L1	0.047	0.082	0.3	4	-10000	0	4
CRKL	0.043	0.09	0.16	174	-10000	0	174
mol:DAG	0.016	0.063	0.21	2	-0.19	28	30
HRAS	0.043	0.1	0.23	61	-0.19	2	63
MAPK8	0.012	0.076	0.16	82	-10000	0	82
RAP1A	0.049	0.093	0.16	187	-10000	0	187
GAB1	0.04	0.087	0.16	161	-10000	0	161
MAPK14	0.034	0.1	0.17	152	-10000	0	152
EPO	0.027	0.02	-10000	0	-0.032	2	2
PLCG1	0.016	0.063	0.21	2	-0.19	28	30
EPOR/TRPC2/IP3 Receptors	0.041	0.013	-10000	0	-0.032	2	2
RAPGEF1	0.035	0.007	-10000	0	0	19	19
EPO/EPOR (dimer)/SOCS3	0.051	0.038	-10000	0	-10000	0	0
GAB1/SHC/GRB2/SOS1	0.06	0.072	0.21	28	-0.11	1	29
EPO/EPOR (dimer)	0.039	0.03	-10000	0	-10000	0	0
IRS2	0.038	0.088	0.16	153	-0.16	4	157
STAT1	0.02	0.066	0.22	6	-0.19	28	34
STAT5B	0.019	0.066	0.21	5	-0.19	29	34
cell proliferation	0.008	0.075	0.16	83	-10000	0	83
GAB1/SHIP/PIK3R1/SHP2/SHC	0.037	0.064	0.16	3	-0.17	7	10
TEC	0.049	0.093	0.16	188	-10000	0	188
SOCS3	0.036	0.004	-10000	0	0	7	7
STAT1 (dimer)	0.02	0.065	0.22	6	-0.18	28	34
JAK2	0.037	0.018	0.076	2	-10000	0	2
PIK3R1	0.032	0.012	-10000	0	0	63	63
EPO/EPOR (dimer)/JAK2	0.047	0.053	0.22	11	-0.091	2	13
EPO/EPOR	0.039	0.03	-10000	0	-10000	0	0
LYN	0.032	0.014	-10000	0	-10000	0	0
TEC/VAV2	0.036	0.085	0.16	149	-10000	0	149
elevation of cytosolic calcium ion concentration	0.041	0.013	-10000	0	-0.032	2	2
SHC1	0.033	0.011	-10000	0	0	52	52
EPO/EPOR (dimer)/LYN	0.04	0.059	-10000	0	-0.13	29	29
mol:IP3	0.016	0.063	0.21	2	-0.19	28	30
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.023	0.093	0.16	135	-0.17	11	146
SH2B3	-0.001	0.006	0.022	19	-10000	0	19
NFKB1	0.034	0.1	0.17	149	-0.2	1	150
EPO/EPOR (dimer)/JAK2/SOCS3	0.015	0.015	-10000	0	-10000	0	0
PTPN6	0.049	0.094	0.17	167	-10000	0	167
TEC/VAV2/GRB2	0.082	0.071	0.23	34	-10000	0	34
EPOR	0.041	0.013	-10000	0	-0.032	2	2
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.06	0.072	0.21	28	-0.11	1	29
SOS1	0	0	-10000	0	-10000	0	0
PLCG2	0.032	0.012	-10000	0	0	63	63
CRKL/CBL/C3G	0.08	0.067	0.22	29	-10000	0	29
VAV2	0.047	0.091	0.16	182	-10000	0	182
CBL	0.049	0.093	0.16	187	-10000	0	187
SHC/Grb2/SOS1	0.021	0.035	-10000	0	-0.1	12	12
STAT5A	0.019	0.065	0.25	2	-0.19	28	30
GRB2	0.035	0.007	-10000	0	0	17	17
STAT5 (dimer)	0.034	0.073	0.27	5	-0.2	8	13
LYN/PLCgamma2	0.026	0.07	-10000	0	-0.17	53	53
PTPN11	0.036	0.005	-10000	0	0	11	11
BTK	0.046	0.093	0.16	185	-10000	0	185
BCL2	0.047	0.082	0.31	1	-10000	0	1

×

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	53	53
SDCBP	0.035	0.007	-10000	0	0	21	21
FGFR/FGF2/Syndecan-1	0.014	0.1	0.21	24	-0.24	10	34
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	0.02	0.1	0.22	19	-0.25	11	30
Syndecan-1/Syntenin	0.025	0.11	0.22	28	-0.24	14	42
MAPK3	0.003	0.1	0.19	23	-0.23	18	41
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	66	66
keratinocyte migration	0.02	0.1	0.22	19	-0.24	11	30
Syndecan-1/RANTES	0.019	0.1	0.23	18	-0.25	10	28
Syndecan-1/CD147	0.023	0.11	0.23	15	-0.24	18	33
Syndecan-1/Syntenin/PIP2	0.022	0.1	0.21	25	-0.23	14	39
LAMA5	0.032	0.012	-10000	0	0	65	65
positive regulation of cell-cell adhesion	0.022	0.1	0.21	25	-0.23	14	39
MMP7	0.027	0.016	-10000	0	0	137	137
HGF	0.024	0.017	-10000	0	0	177	177
Syndecan-1/CASK	-0.001	0.085	0.15	5	-0.23	11	16
Syndecan-1/HGF/MET	0.024	0.089	0.24	10	-0.25	5	15
regulation of cell adhesion	-0.004	0.11	0.22	32	-0.23	20	52
HPSE	0.032	0.012	-10000	0	0	59	59
positive regulation of cell migration	0.014	0.1	0.21	24	-0.24	10	34
SDC1	0.01	0.095	0.17	36	-0.25	9	45
Syndecan-1/Collagen	0.014	0.1	0.21	24	-0.24	10	34
PPIB	0.034	0.01	-10000	0	0	39	39
MET	0.023	0.018	-10000	0	0	191	191
PRKACA	0.035	0.008	-10000	0	0	25	25
MMP9	0.017	0.018	-10000	0	0	267	267
MAPK1	0.003	0.098	0.19	22	-0.24	18	40
homophilic cell adhesion	0.016	0.1	0.21	29	-0.24	10	39
MMP1	0.031	0.013	-10000	0	0	71	71

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.011	0.003	0	32	-0.017	1	33
GNB1/GNG2	0.039	0.03	-10000	0	-0.1	20	20
regulation of S phase of mitotic cell cycle	-0.004	0.081	-10000	0	-0.19	71	71
GNAO1	0.03	0.014	-10000	0	0	87	87
HRAS	0.034	0.009	-10000	0	0	32	32
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	53	-10000	0	53
MAP2K1	-0.035	0.076	0.18	16	-0.18	71	87
T-DHT/AR	0.025	0.008	-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	30	-0.006	76	106
GNAI2	0.033	0.01	-10000	0	0	43	43
GNAI3	0.036	0.006	-10000	0	0	15	15
GNAI1	0.018	0.018	-10000	0	0	263	263
mol:GDP	-0.02	0.036	-10000	0	-0.14	15	15
cell proliferation	-0.059	0.18	0.27	11	-0.42	85	96
PIK3CA	0.031	0.013	-10000	0	0	80	80
FOS	-0.087	0.28	0.38	3	-0.69	83	86
mol:Ca2+	-0.004	0.02	0.028	5	-0.054	57	62
MAPK3	-0.043	0.13	0.25	14	-0.3	78	92
MAPK1	-0.04	0.16	0.25	3	-0.49	37	40
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	0	0.002	0.003	59	-0.004	74	133
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	74	133
HRAS/GTP	0.043	0.065	-10000	0	-0.094	75	75
actin cytoskeleton reorganization	0.019	0.054	-10000	0	-0.12	45	45
SRC	0.035	0.006	-10000	0	0	14	14
voltage-gated calcium channel activity	0	0.002	0.003	59	-0.004	74	133
PI3K	0.019	0.063	-10000	0	-0.13	73	73
apoptosis	0.048	0.19	0.43	84	-0.26	8	92
T-DHT/AR/PELP1	0.043	0.023	-10000	0	-0.1	9	9
HRAS/GDP	0.007	0.06	-10000	0	-0.18	14	14
CREB1	-0.068	0.19	0.27	8	-0.46	84	92
RAC1-CDC42/GTP	0.027	0.06	-10000	0	-0.12	45	45
AR	0.035	0.008	-10000	0	0	22	22
GNB1	0.035	0.007	-10000	0	0	20	20
RAF1	-0.026	0.068	0.19	15	-0.22	13	28
RAC1-CDC42/GDP	0.02	0.053	-10000	0	-0.19	8	8
T-DHT/AR/PELP1/Src	0.06	0.032	-10000	0	-0.086	13	13
MAP2K2	-0.038	0.069	0.16	8	-0.17	68	76
T-DHT/AR/PELP1/Src/PI3K	-0.004	0.081	-10000	0	-0.19	71	71
GNAZ	0.031	0.013	-10000	0	0	81	81
SHBG	0.036	0.006	-10000	0	0	14	14
Gi family/GNB1/GNG2/GDP	-0.038	0.17	-10000	0	-0.45	52	52
mol:T-DHT	0	0.001	0.002	1	-0.004	21	22
RAC1	0.024	0.017	-10000	0	0	173	173
GNRH1	-0.011	0.002	0	12	-10000	0	12
Gi family/GTP	-0.005	0.082	-10000	0	-0.19	62	62
CDC42	0.035	0.008	-10000	0	0	24	24

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.014	0.061	0.14	1	-0.13	69	70
EPHB2	0.034	0.01	-10000	0	0	42	42
Syndecan-2/TACI	0.017	0.055	0.14	1	-0.12	66	67
LAMA1	0	0	-10000	0	-10000	0	0
Syndecan-2/alpha2 ITGB1	0.022	0.073	-10000	0	-0.12	83	83
HRAS	0.034	0.009	-10000	0	0	32	32
Syndecan-2/CASK	-0.009	0.041	0.062	3	-0.11	69	72
ITGA5	0.033	0.011	-10000	0	0	56	56
BAX	-0.009	0.073	-10000	0	-0.9	3	3
EPB41	0.036	0.005	-10000	0	0	9	9
positive regulation of cell-cell adhesion	0.013	0.054	-10000	0	-0.11	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	246	246
Syndecan-2/MMP2	0.009	0.062	0.14	1	-0.14	65	66
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.019	0.054	-10000	0	-0.14	42	42
dendrite morphogenesis	0.015	0.054	0.14	1	-0.12	62	63
Syndecan-2/GM-CSF	0.017	0.055	0.14	1	-0.12	64	65
determination of left/right symmetry	0.007	0.024	0.085	5	-0.24	4	9
Syndecan-2/PKC delta	0.016	0.054	0.14	1	-0.12	62	63
GNB2L1	0.036	0.002	-10000	0	0	2	2
MAPK3	-0.023	0.051	0.11	36	-0.11	64	100
MAPK1	-0.02	0.05	0.12	31	-0.12	52	83
Syndecan-2/RACK1	0.03	0.063	0.14	3	-0.11	77	80
NF1	0.036	0.003	-10000	0	0	4	4
FGFR/FGF/Syndecan-2	0.007	0.024	0.085	5	-0.24	4	9
ITGA2	0.029	0.015	-10000	0	0	112	112
MAPK8	-0.005	0.038	0.13	3	-0.39	3	6
Syndecan-2/alpha2/beta1 Integrin	0.007	0.063	0.14	1	-0.11	92	93
Syndecan-2/Kininogen	0.016	0.054	0.14	1	-0.12	63	64
ITGB1	0.027	0.016	-10000	0	0	138	138
SRC	-0.026	0.051	0.17	11	-0.19	8	19
Syndecan-2/CASK/Protein 4.1	0.015	0.05	-10000	0	-0.1	68	68
extracellular matrix organization	0.014	0.051	-10000	0	-0.12	57	57
actin cytoskeleton reorganization	0.014	0.061	0.14	1	-0.13	69	70
Syndecan-2/Caveolin-2/Ras	0.007	0.067	0.15	2	-0.13	75	77
Syndecan-2/Laminin alpha3	0.016	0.052	0.14	1	-0.12	60	61
Syndecan-2/RasGAP	0.037	0.078	-10000	0	-0.12	89	89
alpha5/beta1 Integrin	0.029	0.042	-10000	0	-0.14	20	20
PRKCD	0.034	0.01	-10000	0	0	40	40
Syndecan-2 dimer	0.015	0.054	0.14	1	-0.12	62	63
GO:0007205	0.001	0.011	-10000	0	-0.12	4	4
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.014	0.067	0.19	1	-0.12	79	80
RHOA	0.035	0.007	-10000	0	0	18	18
SDCBP	0.035	0.007	-10000	0	0	21	21
TNFRSF13B	0.036	0.005	-10000	0	0	8	8
RASA1	0.034	0.009	-10000	0	0	32	32
alpha2/beta1 Integrin	0.019	0.054	-10000	0	-0.14	42	42
Syndecan-2/Synbindin	0.016	0.059	0.14	1	-0.13	67	68
TGFB1	0.032	0.012	-10000	0	0	66	66
CASP3	-0.016	0.052	0.11	32	-0.2	4	36
FN1	0.035	0.009	-10000	0	0	29	29
Syndecan-2/IL8	-0.003	0.069	-10000	0	-0.17	61	61
SDC2	0.007	0.024	0.085	5	-0.24	4	9
KNG1	0.035	0.008	-10000	0	0	28	28
Syndecan-2/Neurofibromin	0.017	0.056	0.14	1	-0.12	68	69
TRAPPC4	0.036	0.006	-10000	0	0	15	15
CSF2	0.036	0.005	-10000	0	0	10	10
Syndecan-2/TGFB1	0.015	0.051	-10000	0	-0.12	57	57
Syndecan-2/Syntenin/PI-4-5-P2	0.013	0.055	-10000	0	-0.11	73	73
Syndecan-2/Ezrin	0.014	0.053	-10000	0	-0.11	70	70
PRKACA	-0.021	0.051	0.12	35	-0.11	63	98
angiogenesis	-0.003	0.068	-10000	0	-0.17	61	61
MMP2	0.029	0.015	-10000	0	0	108	108
IL8	0.019	0.018	-10000	0	0	243	243
calcineurin-NFAT signaling pathway	0.017	0.055	0.14	1	-0.12	66	67

×

IL2 signaling events mediated by STAT5

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
GAB2	0.032	0.014	-10000	0	-0.005	56	56
ELF1	0.042	0.016	-10000	0	-10000	0	0
CCNA2	0.028	0.015	-10000	0	0	117	117
PIK3CA	0.03	0.015	-10000	0	-0.002	87	87
JAK3	0.034	0.012	-10000	0	-0.009	31	31
PIK3R1	0.032	0.014	-10000	0	-0.002	68	68
JAK1	0.033	0.012	-10000	0	-0.003	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	-0.011	0.12	-10000	0	-0.27	89	89
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	0.034	0.011	-10000	0	-0.006	30	30
G1/S transition of mitotic cell cycle	-0.069	0.27	0.28	7	-0.59	92	99
PTPN11	0.035	0.01	-10000	0	-0.03	7	7
CCND2	-0.074	0.19	-10000	0	-0.49	89	89
LCK	0.035	0.01	-10000	0	-0.009	24	24
GRB2	0.035	0.01	-10000	0	-0.009	24	24
IL2	0.035	0.009	-10000	0	-0.012	17	17
CDK6	0.024	0.017	-10000	0	0	176	176
CCND3	-0.026	0.2	0.36	3	-0.74	27	30

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.032	0.012	-10000	0	0	63	63
LAT2	-0.016	0.094	0.16	1	-0.28	46	47
AP1	-0.058	0.18	-10000	0	-0.39	68	68
mol:PIP3	0.021	0.14	0.26	38	-0.28	46	84
IKBKB	0.011	0.094	0.2	36	-0.19	38	74
AKT1	-0.055	0.1	0.25	10	-0.27	41	51
IKBKG	0.01	0.093	0.19	36	-0.19	38	74
MS4A2	0.039	0.008	0.066	4	0	5	9
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.031	0.013	-10000	0	0	80	80
MAP3K1	-0.023	0.12	0.23	9	-0.3	52	61
mol:Ca2+	0.023	0.12	0.23	40	-0.23	36	76
LYN	0.03	0.015	-10000	0	-0.034	6	6
CBLB	-0.023	0.11	0.16	2	-0.28	66	68
SHC1	0.033	0.011	-10000	0	0	52	52
RasGAP/p62DOK	0.048	0.052	-10000	0	-0.12	36	36
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	0.071	0.26	14	-0.17	11	25
PTPN13	-0.036	0.19	-10000	0	-0.6	38	38
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	0.23	8	-0.32	36	44
SYK	0.03	0.015	-10000	0	-0.034	6	6
GRB2	0.036	0.007	-10000	0	0	17	17
LAT/PLCgamma1/GRB2/SLP76/GADs	0.009	0.11	0.2	4	-0.27	55	59
LAT	-0.021	0.11	0.18	3	-0.28	65	68
PAK2	-0.022	0.13	0.22	7	-0.33	52	59
NFATC2	-0.013	0.013	-10000	0	-0.043	69	69
HRAS	-0.02	0.14	0.2	10	-0.35	52	62
GAB2	0.033	0.011	-10000	0	0	47	47
PLA2G1B	-0.005	0.19	-10000	0	-0.92	20	20
Fc epsilon R1	0.042	0.067	-10000	0	-0.11	73	73
Antigen/IgE/Fc epsilon R1	0.044	0.06	-10000	0	-0.093	72	72
mol:GDP	-0.013	0.14	0.21	12	-0.36	49	61
JUN	0.034	0.01	-10000	0	0	40	40
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	158	158
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.015	0.12	-10000	0	-0.29	68	68
CHUK	0.012	0.091	0.19	39	-0.18	39	78
KLRG1	-0.018	0.099	0.14	3	-0.27	49	52
VAV1	-0.021	0.11	0.16	4	-0.28	59	63
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.024	0.11	0.16	2	-0.28	68	70
negative regulation of mast cell degranulation	-0.021	0.092	0.12	1	-0.25	51	52
BTK	-0.012	0.13	-10000	0	-0.37	46	46
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.027	0.11	-10000	0	-0.19	130	130
GAB2/PI3K/SHP2	-0.068	0.073	-10000	0	-0.21	71	71
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.003	0.072	-10000	0	-0.19	57	57
RAF1	-0.007	0.2	-10000	0	-0.97	20	20
Fc epsilon R1/FcgammaRIIB/SHIP	0.024	0.095	-10000	0	-0.13	129	129
FCER1G	0.029	0.016	-10000	0	0	113	113
FCER1A	0.033	0.013	-10000	0	-0.007	42	42
Antigen/IgE/Fc epsilon R1/Fyn	0.041	0.082	-10000	0	-0.11	99	99
MAPK3	-0.004	0.19	-10000	0	-0.9	20	20
MAPK1	-0.013	0.2	-10000	0	-0.95	20	20
NFKB1	0.035	0.007	-10000	0	0	18	18
MAPK8	-0.12	0.28	-10000	0	-0.56	143	143
DUSP1	0.031	0.013	-10000	0	0	77	77
NF-kappa-B/RelA	0.018	0.066	0.14	30	-0.13	36	66
actin cytoskeleton reorganization	-0.027	0.19	-10000	0	-0.6	36	36
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.01	0.15	0.23	9	-0.35	54	63
FER	-0.022	0.12	0.16	3	-0.28	68	71
RELA	0.036	0.005	-10000	0	0	9	9
ITK	0.001	0.04	-10000	0	-0.2	7	7
SOS1	0	0	-10000	0	-10000	0	0
PLCG1	-0.007	0.14	0.22	16	-0.33	50	66
cytokine secretion	0.01	0.045	0.088	26	-0.093	38	64
SPHK1	-0.02	0.12	0.15	4	-0.28	66	70
PTK2	-0.03	0.2	-10000	0	-0.64	36	36
NTAL/PLCgamma1/GRB2/SLP76/GADs	0.025	0.12	0.24	5	-0.28	48	53
EDG1	-0.011	0.003	-10000	0	-10000	0	0
mol:DAG	0.003	0.15	0.25	34	-0.32	47	81
MAP2K2	-0.005	0.2	-10000	0	-0.92	20	20
MAP2K1	-0.017	0.19	-10000	0	-0.92	20	20
MAP2K7	0.035	0.008	-10000	0	0	24	24
KLRG1/SHP2	0.001	0.097	0.2	8	-0.25	46	54
MAP2K4	0.025	0.14	-10000	0	-0.9	11	11
Fc epsilon R1/FcgammaRIIB	0.026	0.1	-10000	0	-0.14	129	129
mol:Choline	-0.031	0.07	0.26	14	-0.17	11	25
SHC/Grb2/SOS1	0.011	0.13	-10000	0	-0.27	67	67
FYN	0.03	0.014	-10000	0	0	90	90
DOK1	0.036	0.002	-10000	0	0	2	2
PXN	-0.03	0.19	-10000	0	-0.59	36	36
HCLS1	-0.025	0.13	0.16	6	-0.32	65	71
PRKCB	0.013	0.12	0.22	39	-0.23	50	89
FCGR2B	0.021	0.018	-10000	0	0	222	222
IGHE	-0.001	0.004	0.021	3	-10000	0	3
KLRG1/SHIP	-0.022	0.094	0.12	1	-0.26	51	52
LCP2	0.031	0.013	-10000	0	0	77	77
PLA2G4A	-0.016	0.12	0.16	10	-0.3	59	69
RASA1	0.034	0.009	-10000	0	0	32	32
mol:Phosphatidic acid	-0.031	0.07	0.26	14	-0.17	11	25
IKK complex	0.008	0.079	0.18	31	-0.16	24	55
WIPF1	0	0	-10000	0	-10000	0	0

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.029	0.085	-10000	0	-0.14	87	87
alphaM/beta2 Integrin/GPIbA	0.049	0.069	-10000	0	-0.12	58	58
alphaM/beta2 Integrin/proMMP-9	-0.008	0.09	-10000	0	-0.13	143	143
PLAUR	0.03	0.014	-10000	0	0	89	89
HMGB1	0.038	0.015	0.082	1	-10000	0	1
alphaM/beta2 Integrin/Talin	0.038	0.071	-10000	0	-0.13	56	56
AGER	0.041	0.01	0.08	2	-10000	0	2
RAP1A	0.036	0.005	-10000	0	0	11	11
SELPLG	0.036	0.004	-10000	0	0	6	6
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.074	0.084	-10000	0	-0.16	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.017	0.018	-10000	0	0	267	267
CYR61	0.025	0.017	-10000	0	0	166	166
TLN1	0.029	0.015	-10000	0	0	102	102
Rap1/GTP	0.028	0.072	-10000	0	-0.22	17	17
RHOA	0.035	0.007	-10000	0	0	18	18
P-selectin oligomer	0.036	0.006	-10000	0	0	14	14
MYH2	0.025	0.071	0.19	2	-0.28	8	10
MST1R	0.035	0.007	-10000	0	0	21	21
leukocyte activation during inflammatory response	0.056	0.064	-10000	0	-0.1	54	54
APOB	0.036	0.006	-10000	0	0	14	14
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	108	108
JAM3	0.033	0.011	-10000	0	0	51	51
GP1BA	0.036	0.005	-10000	0	0	10	10
alphaM/beta2 Integrin/CTGF	0.021	0.085	-10000	0	-0.13	100	100
alphaM/beta2 Integrin	0.024	0.072	0.17	1	-0.24	15	16
JAM3 homodimer	0.033	0.011	-10000	0	0	51	51
ICAM2	0.034	0.009	-10000	0	0	31	31
ICAM1	0.031	0.014	-10000	0	0	84	84
phagocytosis triggered by activation of immune response cell surface activating receptor	0.025	0.075	0.17	1	-0.24	16	17
cell adhesion	0.048	0.068	-10000	0	-0.12	58	58
NFKB1	-0.002	0.078	0.2	23	-10000	0	23
THY1	0.031	0.013	-10000	0	0	79	79
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	0.038	0.1	-10000	0	-0.14	107	107
IL6	-0.015	0.039	-10000	0	-10000	0	0
ITGB2	0.033	0.019	0.077	1	-10000	0	1
elevation of cytosolic calcium ion concentration	0.03	0.085	-10000	0	-0.14	68	68
alphaM/beta2 Integrin/JAM2/JAM3	0.049	0.1	-10000	0	-0.15	86	86
JAM2	0.033	0.012	-10000	0	0	57	57
alphaM/beta2 Integrin/ICAM1	0.077	0.076	-10000	0	-0.12	44	44
alphaM/beta2 Integrin/uPA/Plg	0.041	0.08	-10000	0	-0.13	60	60
RhoA/GTP	0.029	0.073	0.17	11	-0.24	14	25
positive regulation of phagocytosis	0.017	0.1	0.19	2	-0.24	48	50
Ron/MSP	0.051	0.014	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPAR/uPA	0.032	0.087	-10000	0	-0.14	68	68
alphaM/beta2 Integrin/uPAR	0.038	0.076	-10000	0	-0.13	63	63
PLAU	0.019	0.018	-10000	0	0	237	237
PLAT	0.027	0.016	-10000	0	0	128	128
actin filament polymerization	0.027	0.073	0.21	6	-0.27	8	14
MST1	0.035	0.008	-10000	0	0	25	25
alphaM/beta2 Integrin/lipoprotein(a)	0.062	0.068	-10000	0	-0.1	54	54
TNF	0.006	0.088	0.21	19	-10000	0	19
RAP1B	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.019	0.073	-10000	0	-0.14	64	64
fibrinolysis	0.039	0.079	-10000	0	-0.13	55	55
HCK	0.027	0.016	-10000	0	0	128	128
dendritic cell antigen processing and presentation	0.025	0.075	0.17	1	-0.24	16	17
VTN	0.036	0.004	-10000	0	0	6	6
alphaM/beta2 Integrin/CYR61	0.011	0.092	-10000	0	-0.14	119	119
LPA	0.034	0.009	-10000	0	0	33	33
LRP1	0.031	0.013	-10000	0	0	71	71
cell migration	0.001	0.11	0.15	36	-0.14	146	182
FN1	0.035	0.009	-10000	0	0	29	29
alphaM/beta2 Integrin/Thy1	0.031	0.084	-10000	0	-0.13	87	87
MPO	0.036	0.004	-10000	0	0	5	5
KNG1	0.035	0.008	-10000	0	0	28	28
RAP1/GDP	0.024	0.007	-10000	0	-0.11	1	1
ROCK1	0.025	0.073	0.19	2	-0.27	11	13
ELA2	0.034	0.009	-10000	0	0	32	32
PLG	0.034	0.01	-10000	0	0	37	37
CTGF	0.026	0.016	-10000	0	0	141	141
alphaM/beta2 Integrin/Hck	0.031	0.092	-10000	0	-0.18	70	70
ITGAM	0.042	0.01	0.08	2	-10000	0	2
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.071	0.072	-10000	0	-0.12	53	53
HP	0.027	0.016	-10000	0	0	136	136
leukocyte adhesion	0.023	0.12	0.2	1	-0.25	36	37
SELP	0.036	0.006	-10000	0	0	14	14

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.03	0.014	-9999	0	92	92
GPC2	0	0	-9999	-10000	0	0
GPC2/Midkine	0.007	0.05	-9999	-0.13	57	57
neuron projection morphogenesis	0.007	0.05	-9999	-0.13	57	57

×

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	0.6	0.76	31	-1	126	157
IL23A	0.089	0.37	0.78	20	-0.95	23	43
NF kappa B1 p50/RelA/I kappa B alpha	0.08	0.34	0.61	31	-0.84	25	56
positive regulation of T cell mediated cytotoxicity	0.088	0.4	0.76	37	-0.91	27	64
ITGA3	0.088	0.36	0.74	23	-0.89	23	46
IL17F	0.034	0.27	0.51	34	-0.59	28	62
IL12B	0.061	0.079	0.2	70	-0.075	2	72
STAT1 (dimer)	0.07	0.36	0.64	35	-0.89	27	62
CD4	0.071	0.42	0.72	36	-1	33	69
IL23	0.096	0.36	0.73	18	-0.93	22	40
IL23R	0.067	0.14	0.3	81	-0.15	11	92
IL1B	0.083	0.4	0.75	30	-1.1	26	56
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	0.097	0.36	0.68	38	-0.85	22	60
TYK2	0.043	0.059	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	-0.031	4	4
IL12RB1	0.045	0.059	0.15	53	-10000	0	53
PIK3CA	0.031	0.013	-10000	0	0	80	80
IL12Rbeta1/TYK2	0.055	0.074	0.19	38	-0.13	11	49
IL23R/JAK2	0.1	0.16	0.39	72	-0.19	16	88
positive regulation of chronic inflammatory response	0.088	0.4	0.76	37	-0.91	27	64
natural killer cell activation	-0.005	0.011	-10000	0	-0.03	40	40
JAK2	0.056	0.079	0.2	68	-0.075	2	70
PIK3R1	0.032	0.012	-10000	0	0	63	63
NFKB1	0.039	0.009	0.066	2	0	18	20
RELA	0.039	0.008	0.066	2	0	9	11
positive regulation of dendritic cell antigen processing and presentation	0.098	0.35	0.73	18	-0.88	23	41
ALOX12B	0.085	0.36	0.69	30	-0.85	24	54
CXCL1	0.095	0.37	0.74	37	-0.85	24	61
T cell proliferation	0.088	0.4	0.76	37	-0.91	27	64
NFKBIA	0.036	0.014	0.066	2	0	57	59
IL17A	0.058	0.24	0.45	55	-0.46	29	84
PI3K	0.046	0.35	0.62	27	-0.86	27	54
IFNG	0.019	0.033	0.1	26	-0.089	3	29
STAT3 (dimer)	0.048	0.35	0.61	27	-0.83	28	55
IL18R1	0.035	0.008	-10000	0	-0.032	5	5
IL23/IL23R/JAK2/TYK2/SOCS3	0.094	0.27	0.55	51	-0.51	22	73
IL18/IL18R	0.062	0.035	-10000	0	-0.12	7	7
macrophage activation	-0.002	0.016	0.038	1	-0.042	18	19
TNF	0.091	0.36	0.77	19	-0.91	21	40
STAT3/STAT4	0.068	0.36	0.61	29	-0.88	27	56
STAT4 (dimer)	0.07	0.36	0.63	30	-0.89	27	57
IL18	0.031	0.013	-10000	0	-0.03	1	1
IL19	0.098	0.36	0.69	32	-0.85	22	54
STAT5A (dimer)	0.083	0.37	0.64	35	-0.88	27	62
STAT1	0.034	0.01	-10000	0	0	40	40
SOCS3	0.036	0.004	-10000	0	0	7	7
CXCL9	0.099	0.37	0.72	37	-0.84	25	62
MPO	0.086	0.36	0.7	27	-0.86	22	49
positive regulation of humoral immune response	0.088	0.4	0.76	37	-0.91	27	64
IL23/IL23R/JAK2/TYK2	0.086	0.4	0.76	37	-0.95	26	63
IL6	0.15	0.37	0.74	44	-0.86	21	65
STAT5A	0.036	0.004	-10000	0	0	5	5
IL2	0.022	0.03	-10000	0	-0.036	102	102
positive regulation of tyrosine phosphorylation of STAT protein	-0.005	0.011	-10000	0	-0.03	40	40
CD3E	0.086	0.36	0.7	29	-0.88	20	49
keratinocyte proliferation	0.088	0.4	0.76	37	-0.91	27	64
NOS2	0.087	0.36	0.67	38	-0.82	27	65

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.069	0.057	-10000	0	-0.12	32	32
MAP4K1	0.035	0.008	-10000	0	0	26	26
MAP3K8	0.022	0.018	-10000	0	0	196	196
PRKCB	0	0	-10000	0	-10000	0	0
DBNL	0	0	-10000	0	-10000	0	0
CRKL	0.035	0.009	-10000	0	0	29	29
MAP3K1	0	0.054	0.13	1	-0.16	32	33
JUN	-0.14	0.24	-10000	0	-0.51	138	138
MAP3K7	0	0.052	-10000	0	-0.17	30	30
GRAP2	0.034	0.009	-10000	0	0	35	35
CRK	0.035	0.008	-10000	0	0	23	23
MAP2K4	-0.016	0.071	0.15	1	-0.24	22	23
LAT	0.036	0.005	-10000	0	0	10	10
LCP2	0.031	0.013	-10000	0	0	77	77
MAPK8	-0.13	0.25	-10000	0	-0.54	138	138
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.01	0.056	-10000	0	-0.16	33	33
LAT/GRAP2/SLP76/HPK1/HIP-55	0.063	0.054	-10000	0	-0.11	32	32

×

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	0.077	0.19	3	-0.19	38	41
NF kappa B1 p50/RelA/I kappa B alpha	-0.019	0.12	0.25	1	-0.32	44	45
alphaV/beta3 Integrin/Osteopontin/Src	0.026	0.081	-10000	0	-0.16	74	74
AP1	-0.011	0.14	0.28	6	-0.27	81	87
ILK	-0.031	0.072	0.2	2	-0.23	33	35
bone resorption	-0.039	0.083	0.18	6	-0.24	34	40
PTK2B	0.035	0.006	-10000	0	0	16	16
PYK2/p130Cas	0.045	0.09	-10000	0	-0.16	61	61
ITGAV	0.031	0.026	-10000	0	-0.056	35	35
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.02	0.068	-10000	0	-0.14	73	73
alphaV/beta3 Integrin/Osteopontin	0.05	0.092	-10000	0	-0.16	72	72
MAP3K1	-0.03	0.063	0.22	1	-0.2	27	28
JUN	0.034	0.01	-10000	0	0	40	40
MAPK3	-0.031	0.085	0.18	7	-0.24	41	48
MAPK1	-0.029	0.086	0.17	12	-0.25	38	50
Rac1/GDP	0.017	0.019	-10000	0	-0.13	5	5
NFKB1	0.035	0.007	-10000	0	0	18	18
MAPK8	-0.027	0.059	0.23	1	-0.2	26	27
ITGB3	0.032	0.026	-10000	0	-0.055	39	39
NFKBIA	-0.038	0.11	0.18	5	-0.31	46	51
FOS	0.026	0.017	-10000	0	0	158	158
CD44	0.029	0.015	-10000	0	0	110	110
CHUK	0.025	0.017	-10000	0	0	163	163
PLAU	-0.071	0.25	-10000	0	-0.97	32	32
NF kappa B1 p50/RelA	-0.001	0.12	-10000	0	-0.33	39	39
BCAR1	0	0	-10000	0	-10000	0	0
RELA	0.036	0.005	-10000	0	0	9	9
alphaV beta3 Integrin	0.04	0.058	-10000	0	-0.13	39	39
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.032	0.065	0.19	2	-0.23	29	31
VAV3	-0.024	0.072	0.15	6	-0.22	33	39
MAP3K14	-0.028	0.074	0.17	5	-0.21	35	40
ROCK2	0.035	0.007	-10000	0	0	21	21
SPP1	0.03	0.026	-10000	0	-0.058	29	29
RAC1	0.024	0.017	-10000	0	0	173	173
Rac1/GTP	-0.021	0.07	0.14	4	-0.22	29	33
MMP2	-0.061	0.12	-10000	0	-0.32	61	61

×

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	20	20
regulation of centriole replication	-0.011	0.032	0.092	43	-9999	0	43

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.028	0.015	-10000	0	0	116	116
EPHB2	0.034	0.011	-10000	0	0	42	42
EFNB1	-0.017	0.02	0.084	8	-10000	0	8
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.047	0.053	-10000	0	-0.12	13	13
Ephrin B2/EPHB1-2	0.031	0.056	-10000	0	-0.1	52	52
neuron projection morphogenesis	0.032	0.041	-10000	0	-0.12	13	13
Ephrin B1/EPHB1-2/Tiam1	0.057	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	0.2	1	-0.52	52	53
YES1	-0.055	0.24	-10000	0	-0.75	52	52
Ephrin B1/EPHB1-2/NCK2	0.061	0.044	-10000	0	-0.1	20	20
PI3K	-0.02	0.19	-10000	0	-0.56	51	51
mol:GDP	0.055	0.048	-10000	0	-0.1	28	28
ITGA2B	0.036	0.004	-10000	0	0	5	5
endothelial cell proliferation	0.015	0.047	-10000	0	-0.11	46	46
FYN	-0.067	0.24	-10000	0	-0.77	52	52
MAP3K7	-0.051	0.16	0.22	1	-0.54	51	52
FGR	-0.051	0.23	-10000	0	-0.73	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	0.008	-10000	0	0	23	23
cell adhesion	-0.032	0.17	-10000	0	-0.53	51	51
LYN	-0.062	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	-0.048	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	95	95
EPHB4	0.025	0.017	-10000	0	0	166	166
RAC1	0.024	0.017	-10000	0	0	173	173
Ephrin B2/EPHB4	0.016	0.047	-10000	0	-0.11	46	46
alphaIIb/beta3 Integrin	0.054	0.006	-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	-0.059	0.043	0.1	20	-10000	0	20
MAPK8	-0.056	0.15	-10000	0	-0.49	52	52
Ephrin B1/EPHB1-2/RGS3	0.066	0.035	-10000	0	-0.11	6	6
endothelial cell migration	0.01	0.17	0.2	113	-0.45	43	156
NCK2	0.035	0.007	-10000	0	0	17	17
PTPN13	0.034	0.013	-10000	0	0	60	60
regulation of focal adhesion formation	-0.059	0.043	0.1	20	-10000	0	20
chemotaxis	-0.064	0.034	0.11	6	-10000	0	6
PIK3CA	0.031	0.013	-10000	0	0	80	80
Rac1/GTP	0.04	0.047	-10000	0	-0.12	13	13
angiogenesis	-0.047	0.18	-10000	0	-0.57	51	51
LCK	-0.049	0.23	-10000	0	-0.72	51	51

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.044	0.042	-10000	0	-0.14	24	24
AKT1	-0.017	0.17	0.28	16	-0.43	43	59
PTK2B	-0.001	0.11	0.2	56	-0.36	13	69
VEGFR2 homodimer/Frs2	0.026	0.082	0.18	5	-0.31	17	22
CAV1	0.016	0.018	-10000	0	0	290	290
CALM1	0.033	0.011	-10000	0	0	54	54
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.022	0.085	0.18	2	-0.29	19	21
endothelial cell proliferation	0.011	0.14	0.28	30	-0.38	29	59
mol:Ca2+	0.006	0.13	0.23	67	-0.32	20	87
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.017	0.087	0.2	2	-0.27	23	25
RP11-342D11.1	-0.005	0.1	0.17	69	-0.23	46	115
CDH5	0.03	0.014	-10000	0	0	92	92
VEGFA homodimer	0.036	0.034	-10000	0	-0.094	14	14
SHC1	0.033	0.011	-10000	0	0	52	52
SHC2	0.032	0.012	-10000	0	0	64	64
HRAS/GDP	0.005	0.09	-10000	0	-0.24	46	46
SH2D2A	0.036	0.006	-10000	0	0	15	15
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.021	0.11	0.26	5	-0.33	24	29
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.022	0.086	0.18	2	-0.3	19	21
VEGFR1 homodimer	0.034	0.009	-10000	0	0	33	33
SHC/GRB2/SOS1	0.036	0.1	-10000	0	-0.23	47	47
GRB10	-0.011	0.11	0.21	32	-0.32	34	66
PTPN11	0.036	0.005	-10000	0	0	11	11
GRB2	0.035	0.007	-10000	0	0	17	17
PAK1	0.036	0.006	-10000	0	0	15	15
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.037	0.12	0.22	2	-0.27	38	40
HRAS	0.034	0.009	-10000	0	0	32	32
VEGF/Rho/ROCK1/Integrin Complex	0.012	0.1	0.18	5	-0.32	30	35
HIF1A	0.033	0.01	-10000	0	0	44	44
FRS2	0.034	0.009	-10000	0	0	30	30
oxygen and reactive oxygen species metabolic process	0.016	0.085	0.19	2	-0.27	23	25
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.036	0.006	-10000	0	0	12	12
Nck/Pak	0.049	0.023	-10000	0	-0.14	5	5
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.01	0.1	0.18	2	-0.28	32	34
mol:GDP	0.017	0.093	-10000	0	-0.23	47	47
mol:NADP	0.032	0.12	0.3	22	-0.32	19	41
eNOS/Hsp90	0.029	0.12	0.29	21	-0.3	20	41
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	0.006	0.13	0.23	67	-0.32	20	87
HIF1A/ARNT	0.046	0.031	-10000	0	-0.14	11	11
SHB	0.033	0.011	-10000	0	0	51	51
VEGFA	-0.003	0.013	-10000	0	-0.039	52	52
VEGFC	0.033	0.011	-10000	0	0	51	51
FAK1/Vinculin	0.012	0.12	0.26	13	-0.44	19	32
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.035	0.007	-10000	0	0	18	18
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.037	0.1	0.2	5	-0.28	26	31
PTPN6	0.033	0.011	-10000	0	0	51	51
EPAS1	0.032	0.062	-10000	0	-0.26	14	14
mol:L-citrulline	0.032	0.12	0.3	22	-0.32	19	41
ITGAV	0.034	0.009	-10000	0	0	31	31
PIK3CA	0.031	0.013	-10000	0	0	80	80
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.039	0.094	0.2	5	-0.27	22	27
VEGFR2 homodimer/VEGFA homodimer	0.012	0.097	-10000	0	-0.25	47	47
VEGFR2/3 heterodimer	0.026	0.084	0.18	5	-0.31	18	23
VEGFB	0.036	0.005	-10000	0	0	8	8
MAPK11	0.009	0.13	0.28	37	-0.34	20	57
VEGFR2 homodimer	-0.006	0.081	0.17	4	-0.38	15	19
FLT1	0.034	0.009	-10000	0	0	33	33
NEDD4	0.029	0.033	0.092	7	-0.057	53	60
MAPK3	0.012	0.12	0.28	41	-0.3	20	61
MAPK1	0.01	0.13	0.27	43	-0.29	21	64
VEGFA145/NRP2	0.023	0.022	-10000	0	-0.047	5	5
VEGFR1/2 heterodimer	0.024	0.083	0.18	4	-0.32	17	21
KDR	-0.006	0.082	0.17	4	-0.38	15	19
VEGFA165/NRP1/VEGFR2 homodimer	0.024	0.098	0.2	12	-0.23	47	59
SRC	0.036	0.006	-10000	0	0	14	14
platelet activating factor biosynthetic process	0.012	0.13	0.28	42	-0.3	20	62
PI3K	-0.001	0.14	0.27	18	-0.38	34	52
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.021	0.086	0.18	2	-0.3	19	21
FES	0.007	0.13	0.24	68	-0.33	19	87
GAB1	0.012	0.12	0.24	16	-0.36	26	42
VEGFR2 homodimer/VEGFA homodimer/Src	0.021	0.086	0.17	1	-0.3	19	20
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	5	5
eNOS/Caveolin-1	0.009	0.095	0.29	4	-0.34	16	20
VEGFR2 homodimer/VEGFA homodimer/Yes	0.018	0.09	0.18	1	-0.3	21	22
PI3K/GAB1	-0.003	0.16	0.27	24	-0.4	46	70
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.06	0.097	0.23	2	-0.26	19	21
PRKACA	0.035	0.008	-10000	0	0	25	25
VEGFR2/3 heterodimer/VEGFC homodimer	0.038	0.08	0.2	1	-0.28	16	17
HSP90AA1	0	0	-10000	0	-10000	0	0
CDC42	0.007	0.13	0.23	67	-0.34	17	84
actin cytoskeleton reorganization	0.022	0.086	0.18	2	-0.3	19	21
PTK2	0.009	0.13	0.25	22	-0.45	20	42
EDG1	0	0.14	0.23	66	-0.34	30	96
mol:DAG	0.006	0.13	0.23	67	-0.32	20	87
CaM/Ca2+	0.02	0.12	0.26	29	-0.24	47	76
MAP2K3	0	0.12	0.23	55	-0.32	18	73
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.046	0.14	0.23	102	-0.3	43	145
PLCG1	0.006	0.13	0.23	67	-0.33	20	87
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.035	0.091	0.2	4	-0.28	19	23
IQGAP1	0.033	0.011	-10000	0	0	51	51
YES1	0.034	0.01	-10000	0	0	41	41
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.021	0.089	0.18	2	-0.3	21	23
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.019	0.086	0.18	2	-0.28	20	22
cell migration	0.007	0.14	0.25	23	-0.38	33	56
mol:PI-3-4-5-P3	0.001	0.14	0.25	22	-0.35	34	56
FYN	0.03	0.014	-10000	0	0	90	90
VEGFB/NRP1	0.006	0.12	0.22	67	-0.32	18	85
mol:NO	0.032	0.12	0.3	22	-0.32	19	41
PXN	0.036	0.004	-10000	0	0	7	7
HRAS/GTP	-0.045	0.069	-10000	0	-0.24	46	46
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.006	0.097	-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	0.031	0.13	0.32	19	-0.35	20	39
VEGFR2 homodimer/VEGFA homodimer/Sck	0.015	0.093	-10000	0	-0.28	27	27
RAC1	0.024	0.017	-10000	0	0	173	173
PRKCA	0	0.12	0.23	58	-0.31	20	78
PRKCB	0.004	0.12	0.22	67	-0.3	20	87
VCL	0.025	0.017	-10000	0	0	154	154
VEGFA165/NRP1	-0.025	0.082	0.12	39	-0.23	47	86
VEGFR1/2 heterodimer/VEGFA homodimer	0.02	0.086	0.18	2	-0.3	19	21
VEGFA165/NRP2	0.023	0.022	-10000	0	-0.047	5	5
MAPKKK cascade	-0.031	0.091	0.17	8	-0.32	33	41
NRP2	0.036	0.005	-10000	0	0	8	8
VEGFC homodimer	0.033	0.011	-10000	0	0	51	51
NCK1	0.035	0.008	-10000	0	0	27	27
ROCK1	0.036	0.006	-10000	0	0	15	15
FAK1/Paxillin	0.027	0.13	0.26	17	-0.43	20	37
MAP3K13	0.007	0.13	0.24	66	-0.33	18	84
PDPK1	-0.017	0.13	0.22	37	-0.34	31	68

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	-0.032	0.17	-10000	0	-0.47	65	65
HDAC1	0.027	0.034	0.089	21	-0.039	84	105
AES	0.033	0.013	0.071	8	-0.004	46	54
FBXW11	0.035	0.008	-10000	0	0	25	25
DTX1	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.033	0.027	-10000	0	-10000	0	0
TLE1	0.034	0.013	0.068	8	-0.007	36	44
AP1	-0.01	0.073	-10000	0	-0.2	55	55
NCSTN	0.035	0.008	-10000	0	0	28	28
ADAM10	0.033	0.012	-10000	0	0	56	56
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.011	0.12	-10000	0	-0.52	8	8
NICD/RBPSUH	-0.035	0.17	-10000	0	-0.47	65	65
WIF1	0.028	0.015	-10000	0	0	112	112
NOTCH1	-0.031	0.18	-10000	0	-0.49	64	64
PSENEN	0.035	0.008	-10000	0	0	28	28
KREMEN2	0.036	0.004	-10000	0	0	7	7
DKK1	0.017	0.018	-10000	0	0	271	271
beta catenin/beta TrCP1	0.062	0.091	0.23	18	-0.3	8	26
APH1B	0.035	0.006	-10000	0	0	16	16
APH1A	0.036	0.005	-10000	0	0	11	11
AXIN1	0.013	0.065	0.25	1	-10000	0	1
CtBP/CBP/TCF1/TLE1/AES	0.012	0.072	0.17	48	-0.18	19	67
PSEN1	0.033	0.011	-10000	0	0	46	46
FOS	0.025	0.017	-10000	0	0	158	158
JUN	0.034	0.01	-10000	0	0	40	40
MAP3K7	0.032	0.018	0.062	9	-0.011	61	70
CTNNB1	0.048	0.088	0.22	24	-0.3	6	30
MAPK3	0.036	0.004	-10000	0	0	6	6
DKK2/LRP6/Kremen 2	0.064	0.027	-10000	0	-0.12	1	1
HNF1A	0	0.006	0.032	9	-10000	0	9
CTBP1	0.034	0.013	0.072	6	-0.007	34	40
MYC	-0.079	0.37	-10000	0	-1.2	50	50
NKD1	0	0.003	-10000	0	-10000	0	0
FZD1	0.024	0.017	-10000	0	0	173	173
NOTCH1 precursor/Deltex homolog 1	-0.035	0.17	-10000	0	-0.47	65	65
apoptosis	-0.01	0.073	-10000	0	-0.2	56	56
Delta 1/NOTCHprecursor	-0.035	0.17	-10000	0	-0.47	65	65
DLL1	0	0	-10000	0	-10000	0	0
PPARD	0.025	0.036	-10000	0	-10000	0	0
Gamma Secretase	0.08	0.07	-10000	0	-0.15	28	28
APC	-0.023	0.17	0.23	1	-0.62	31	32
DVL1	0.019	0.096	-10000	0	-0.41	18	18
CSNK2A1	0.034	0.009	-10000	0	0	31	31
MAP3K7IP1	0.032	0.018	0.063	8	-0.012	55	63
DKK1/LRP6/Kremen 2	0.031	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	14	14
NLK	0.011	0.051	0.13	1	-0.21	20	21
CCND1	-0.047	0.34	-10000	0	-1.2	40	40
WNT1	0.035	0.006	-10000	0	0	16	16
Axin1/APC/beta catenin	0.012	0.13	0.24	1	-0.42	29	30
DKK2	0.034	0.009	-10000	0	0	31	31
NOTCH1 precursor/DVL1	-0.009	0.19	-10000	0	-0.48	59	59
GSK3B	0.034	0.01	-10000	0	0	40	40
FRAT1	0.025	0.017	-10000	0	0	161	161
NOTCH/Deltex homolog 1	-0.032	0.17	-10000	0	-0.47	65	65
PPP2R5D	0.027	0.037	-10000	0	-0.25	4	4
MAPK1	0.033	0.01	-10000	0	0	45	45
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	4	-0.019	62	66

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.001	0.047	-10000	0	-10000	0	0
PLK1	-0.059	0.2	-10000	0	-0.79	12	12
CDKN1B	-0.11	0.21	0.4	4	-0.39	108	112
FOXO3	-0.065	0.22	0.33	5	-0.49	81	86
KAT2B	-0.001	0.021	0.047	17	-0.042	75	92
FOXO1/SIRT1	0.014	0.048	-10000	0	-0.24	5	5
CAT	-0.075	0.26	-10000	0	-1.1	18	18
CTNNB1	0.036	0.006	-10000	0	0	15	15
AKT1	0.021	0.042	-10000	0	-0.063	54	54
FOXO1	0.004	0.051	0.22	1	-0.26	6	7
MAPK10	0.044	0.093	0.19	129	-0.15	18	147
mol:GTP	-0.001	0.004	-10000	0	-0.021	1	1
FOXO4	-0.031	0.2	0.26	15	-0.44	63	78
response to oxidative stress	0	0.023	0.052	13	-0.049	35	48
FOXO3A/SIRT1	-0.06	0.21	-10000	0	-0.47	83	83
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	0.02	0.054	-10000	0	-0.24	6	6
mol:GDP	0	0.023	0.052	13	-0.049	35	48
RAN	0.034	0.011	-10000	0	-0.015	20	20
GADD45A	-0.15	0.33	0.47	1	-0.87	68	69
YWHAQ	0.036	0.005	-10000	0	0	9	9
FOXO1/14-3-3 family	0.005	0.15	-10000	0	-0.56	19	19
MST1	0.022	0.043	0.11	1	-0.06	84	85
CSNK1D	0.035	0.007	-10000	0	0	20	20
CSNK1E	0.032	0.012	-10000	0	0	67	67
FOXO4/14-3-3 family	-0.003	0.15	-10000	0	-0.46	29	29
YWHAB	0.035	0.008	-10000	0	0	24	24
MAPK8	0.024	0.076	0.18	76	-0.14	12	88
MAPK9	0.052	0.097	0.19	150	-0.15	15	165
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	0.42	4	-0.79	92	96
RBL2	-0.072	0.28	-10000	0	-0.93	36	36
RAL/GDP	0.018	0.049	-10000	0	-0.14	20	20
CHUK	0.012	0.038	-10000	0	-0.059	71	71
Ran/GTP	0.019	0.025	-10000	0	-0.12	6	6
CSNK1G2	0.034	0.009	-10000	0	0	30	30
RAL/GTP	0.017	0.051	0.14	2	-0.13	20	22
CSNK1G1	0.036	0.006	-10000	0	0	14	14
FASLG	0.022	0.041	-10000	0	-0.59	1	1
SKP2	0.035	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	89	90
CCNB1	-0.16	0.42	0.49	1	-1.1	83	84
FOXO1-3a-4/beta catenin	-0.039	0.21	0.36	12	-0.4	78	90
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.054	-10000	0	-0.24	6	6
CSNK1A1	0.036	0.006	-10000	0	0	14	14
SGK1	-0.001	0.021	0.047	17	-0.042	75	92
CSNK1G3	0.036	0.006	-10000	0	0	13	13
Ran/GTP/Exportin 1	0.039	0.036	-10000	0	-0.12	9	9
ZFAND5	-0.019	0.16	0.24	16	-0.35	62	78
SFN	0.031	0.013	-10000	0	0	78	78
CDK2	0.036	0.012	-10000	0	-0.031	3	3
FOXO3A/14-3-3	-0.012	0.16	-10000	0	-0.47	31	31
CREBBP	0.038	0.008	-10000	0	-0.031	3	3
FBXO32	-0.059	0.2	0.32	1	-0.44	81	82
BCL6	-0.093	0.32	-10000	0	-0.99	47	47
RALB	0.033	0.013	-10000	0	-0.015	32	32
RALA	0.023	0.018	-10000	0	-0.001	184	184
YWHAH	0.031	0.013	-10000	0	0	73	73

×

FAS signaling pathway (CD95)

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
SPTAN1	-0.017	0.056	0.22	8	-0.21	21	29
RFC1	-0.02	0.048	0.18	2	-0.21	25	27
PRKDC	-0.016	0.055	0.19	7	-0.21	23	30
RIPK1	0.027	0.021	-10000	0	-0.023	73	73
CASP7	-0.16	0.28	-10000	0	-0.57	162	162
FASLG/FAS/FADD/FAF1	-0.012	0.083	0.16	27	-0.18	44	71
MAP2K4	-0.043	0.14	0.21	2	-0.31	41	43
mol:ceramide	0.004	0.089	0.18	5	-0.23	19	24
GSN	-0.008	0.058	0.19	11	-0.22	19	30
FASLG/FAS/FADD/FAF1/Caspase 8	-0.011	0.093	0.18	12	-0.24	25	37
FAS	0.021	0.02	-10000	0	0	238	238
BID	-0.031	0.033	0.076	9	-0.13	21	30
MAP3K1	-0.1	0.19	-10000	0	-0.36	166	166
MAP3K7	0.035	0.01	-10000	0	0	41	41
RB1	-0.017	0.045	0.23	1	-0.21	23	24
CFLAR	0.029	0.021	-10000	0	-0.027	59	59
HGF/MET	0.034	0.049	-10000	0	-0.12	22	22
ARHGDIB	-0.016	0.055	0.22	6	-0.22	21	27
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	0.1	-10000	0	-0.63	10	10
MAPK8	-0.033	0.13	0.23	2	-0.34	22	24
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	0.052	-10000	0	-0.12	27	27
CFLAR/RIP1	0.048	0.02	-10000	0	-0.13	2	2
FAIM3	0.033	0.009	-10000	0	0	36	36
FAF1	0.038	0.012	-10000	0	-10000	0	0
PARP1	-0.019	0.048	0.22	1	-0.21	26	27
DFFB	-0.016	0.046	0.22	2	-0.21	23	25
CHUK	0.015	0.096	-10000	0	-0.6	10	10
FASLG	0.039	0.008	-10000	0	-10000	0	0
FAS/FADD	0.021	0.053	-10000	0	-0.14	34	34
HGF	0.024	0.017	-10000	0	0	177	177
LMNA	-0.02	0.049	0.2	5	-0.19	24	29
CASP6	-0.017	0.047	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	0.013	0.084	3	-10000	0	3
IL6	0.02	0.13	-10000	0	-0.61	6	6
MET	0.023	0.018	-10000	0	0	191	191
ICAD/CAD	-0.021	0.049	0.25	4	-0.2	23	27
FASLG/FAS/FADD/FAF1/Caspase 10	0.004	0.09	0.18	5	-0.24	19	24
activation of caspase activity by cytochrome c	-0.031	0.033	0.073	26	-0.13	23	49
PAK2	-0.015	0.049	0.14	2	-0.2	25	27
BCL2	0.035	0.007	-10000	0	0	20	20

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.004	0.093	-10000	0	-0.4	5	5
UGCG	-0.027	0.19	-10000	0	-0.74	31	31
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.006	0.13	0.26	8	-0.34	38	46
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.026	0.19	-10000	0	-0.72	31	31
mol:DAG	-0.007	0.032	0.17	15	-10000	0	15
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.024	0.18	0.29	8	-0.42	62	70
FRAP1	-0.034	0.2	0.3	9	-0.48	61	70
FOXO3	-0.033	0.2	0.3	8	-0.46	64	72
AKT1	-0.039	0.21	0.31	7	-0.5	64	71
GAB2	0.03	0.019	-10000	0	-0.012	80	80
SMPD1	0.003	0.09	-10000	0	-0.49	14	14
SGMS1	-0.003	0.034	0.066	18	-0.07	73	91
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	0.045	0.094	5	-0.13	73	78
CALM1	0.033	0.011	-10000	0	0	54	54
cell proliferation	-0.032	0.19	0.28	10	-0.39	69	79
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	0.018	0.077	-10000	0	-0.16	73	73
RPS6KB1	0.029	0.027	-10000	0	-10000	0	0
mol:sphingomyelin	-0.007	0.032	0.17	15	-10000	0	15
natural killer cell activation	0	0.003	0.007	26	-0.01	45	71
JAK3	0.034	0.016	-10000	0	-0.028	22	22
PIK3R1	0.031	0.019	-10000	0	-0.029	24	24
JAK1	0.032	0.019	-10000	0	-0.028	29	29
NFKB1	0.035	0.007	-10000	0	0	18	18
MYC	-0.065	0.29	0.45	7	-0.83	56	63
MYB	0.034	0.041	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.025	0.16	0.25	9	-0.38	55	64
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	0.26	10	-0.37	54	64
Rac1/GDP	0.004	0.05	0.12	6	-0.13	46	52
T cell proliferation	-0.023	0.15	0.26	8	-0.35	53	61
SHC1	0.029	0.019	-10000	0	-0.011	85	85
RAC1	0.024	0.017	-10000	0	0	173	173
positive regulation of cyclin-dependent protein kinase activity	0.005	0.012	0.057	24	-10000	0	24
PRKCZ	-0.025	0.15	0.26	8	-0.36	54	62
NF kappa B1 p50/RelA	-0.011	0.19	0.31	8	-0.43	61	69
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.006	0.094	0.21	3	-0.31	20	23
HSP90AA1	0	0	-10000	0	-10000	0	0
RELA	0.036	0.005	-10000	0	0	9	9
IL2RA	0.021	0.021	-10000	0	-0.004	198	198
IL2RB	0.032	0.018	-10000	0	-0.028	22	22
TERT	0.036	0.006	-10000	0	0	14	14
E2F1	0.036	0.031	-10000	0	-10000	0	0
SOS1	0	0.003	0.008	32	-0.009	44	76
RPS6	0.031	0.013	-10000	0	0	81	81
mol:cAMP	-0.003	0.007	-10000	0	-0.031	25	25
PTPN11	0.032	0.018	-10000	0	-0.023	47	47
IL2RG	0.034	0.017	-10000	0	-0.03	24	24
actin cytoskeleton organization	-0.023	0.15	0.26	8	-0.35	53	61
GRB2	0.033	0.016	-10000	0	-0.017	42	42
IL2	0.035	0.016	-10000	0	-0.03	24	24
PIK3CA	0.03	0.02	-10000	0	-0.029	26	26
Rac1/GTP	0.026	0.064	0.16	5	-0.12	46	51
LCK	0.034	0.017	-10000	0	-0.03	25	25
BCL2	-0.02	0.16	-10000	0	-0.43	35	35

×

BCR signaling pathway

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
JUN	0.003	0.12	0.26	3	-0.31	31	34
IKBKB	0.017	0.078	0.26	4	-0.29	5	9
AKT1	0.001	0.083	0.22	27	-0.18	13	40
IKBKG	0.009	0.07	0.23	1	-0.24	9	10
CALM1	-0.029	0.12	0.21	3	-0.35	46	49
PIK3CA	0.031	0.013	-10000	0	0	80	80
MAP3K1	0.027	0.13	0.28	10	-0.34	31	41
MAP3K7	0.034	0.01	-10000	0	0	41	41
mol:Ca2+	-0.027	0.13	0.22	4	-0.37	45	49
DOK1	0.036	0.002	-10000	0	0	2	2
AP-1	-0.009	0.092	0.19	11	-0.22	38	49
LYN	0.031	0.013	-10000	0	0	74	74
BLNK	0.019	0.018	-10000	0	0	243	243
SHC1	0.033	0.011	-10000	0	0	52	52
BCR complex	0.05	0.015	-10000	0	-10000	0	0
CD22	-0.016	0.092	-10000	0	-0.29	35	35
CAMK2G	-0.018	0.12	0.21	4	-0.33	45	49
CSNK2A1	0.034	0.009	-10000	0	0	31	31
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.036	0.054	-10000	0	-0.2	24	24
GO:0007205	-0.028	0.14	0.22	4	-0.38	45	49
SYK	0.031	0.013	-10000	0	0	76	76
ELK1	-0.033	0.13	0.21	4	-0.36	45	49
NFATC1	-0.017	0.092	0.25	4	-0.26	32	36
B-cell antigen/BCR complex	0.05	0.015	-10000	0	-10000	0	0
PAG1/CSK	0.023	0.022	-10000	0	-0.13	10	10
NFKBIB	0.02	0.042	0.14	1	-0.13	19	20
HRAS	-0.028	0.12	0.18	7	-0.31	49	56
NFKBIA	0.02	0.039	0.14	1	-0.12	15	16
NF-kappa-B/RelA/I kappa B beta	0.025	0.038	0.14	1	-0.11	11	12
RasGAP/Csk	0.045	0.096	-10000	0	-0.12	113	113
mol:GDP	-0.026	0.13	0.22	4	-0.36	45	49
PTEN	0.026	0.017	-10000	0	0	148	148
CD79B	0.036	0.005	-10000	0	0	10	10
NF-kappa-B/RelA/I kappa B alpha	0.025	0.036	0.14	1	-0.11	8	9
GRB2	0.035	0.007	-10000	0	0	17	17
PI3K/BCAP/CD19	-0.038	0.16	0.38	1	-0.43	45	46
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	-0.026	0.13	0.23	4	-0.38	44	48
CSK	0.035	0.007	-10000	0	0	21	21
FOS	-0.031	0.13	0.2	7	-0.35	48	55
CHUK	-0.061	0.14	0.23	1	-0.26	124	125
IBTK	0.034	0.009	-10000	0	0	30	30
CARD11/BCL10/MALT1/TAK1	-0.003	0.13	0.23	1	-0.33	40	41
PTPN6	-0.021	0.094	0.18	8	-0.3	34	42
RELA	0.036	0.005	-10000	0	0	9	9
BCL2A1	0.017	0.034	0.095	12	-0.096	16	28
VAV2	-0.014	0.1	-10000	0	-0.31	34	34
ubiquitin-dependent protein catabolic process	0.021	0.042	0.14	1	-0.13	19	20
BTK	0.019	0.012	-10000	0	-10000	0	0
CD19	-0.016	0.093	-10000	0	-0.29	36	36
MAP4K1	0.035	0.008	-10000	0	0	26	26
CD72	0.033	0.011	-10000	0	0	55	55
PAG1	0	0	-10000	0	-10000	0	0
MAPK14	0.023	0.12	0.25	10	-0.3	31	41
SH3BP5	0.033	0.011	-10000	0	0	51	51
PIK3AP1	-0.023	0.14	0.23	4	-0.39	45	49
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.036	0.18	-10000	0	-0.52	49	49
RAF1	-0.033	0.11	0.19	5	-0.3	49	54
RasGAP/p62DOK/SHIP	0.037	0.084	-10000	0	-0.11	112	112
CD79A	0.034	0.009	-10000	0	0	34	34
re-entry into mitotic cell cycle	-0.01	0.092	0.18	11	-0.22	39	50
RASA1	0.034	0.009	-10000	0	0	32	32
MAPK3	-0.038	0.096	0.18	3	-0.29	38	41
MAPK1	-0.037	0.099	0.19	4	-0.3	39	43
CD72/SHP1	-0.002	0.1	0.26	7	-0.29	36	43
NFKB1	0.035	0.007	-10000	0	0	18	18
MAPK8	0.022	0.12	0.25	12	-0.3	28	40
actin cytoskeleton organization	0.034	0.11	0.24	22	-0.29	19	41
NF-kappa-B/RelA	0.042	0.087	0.26	1	-0.26	16	17
Calcineurin	-0.009	0.13	0.24	2	-0.32	45	47
PI3K	-0.031	0.085	-10000	0	-0.27	34	34
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.018	0.14	0.24	4	-0.38	49	53
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	0.015	0.15	-10000	0	-0.62	8	8
DAPP1	-0.004	0.15	-10000	0	-0.7	8	8
cytokine secretion	-0.015	0.088	0.25	4	-0.25	32	36
mol:DAG	-0.026	0.13	0.23	4	-0.38	44	48
PLCG2	0.032	0.012	-10000	0	0	63	63
MAP2K1	-0.036	0.1	0.18	4	-0.3	46	50
B-cell antigen/BCR complex/FcgammaRIIB	0.016	0.074	-10000	0	-0.12	96	96
mol:PI-3-4-5-P3	-0.018	0.07	0.18	20	-0.21	16	36
ETS1	-0.029	0.11	0.21	5	-0.31	46	51
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.034	0.091	-10000	0	-0.15	60	60
B-cell antigen/BCR complex/LYN	-0.011	0.098	-10000	0	-0.3	38	38
MALT1	0.034	0.009	-10000	0	0	32	32
TRAF6	0.036	0.005	-10000	0	0	10	10
RAC1	0.031	0.12	0.26	14	-0.31	19	33
B-cell antigen/BCR complex/LYN/SYK	0.023	0.11	-10000	0	-0.28	33	33
CARD11	-0.027	0.13	0.22	4	-0.36	45	49
FCGR2B	0.021	0.018	-10000	0	0	222	222
PPP3CA	0.034	0.01	-10000	0	0	38	38
BCL10	0.035	0.007	-10000	0	0	20	20
IKK complex	0.003	0.043	0.12	5	-0.12	8	13
PTPRC	0.029	0.015	-10000	0	0	110	110
PDPK1	-0.015	0.056	0.15	20	-0.16	11	31
PPP3CB	0.025	0.017	-10000	0	0	157	157
PPP3CC	0.036	0.006	-10000	0	0	13	13
POU2F2	0.015	0.03	0.09	2	-0.087	16	18

×

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	0.03	0.04	0.14	36	-10000	0	36
Ephrin B/EPHB2/RasGAP	0.058	0.09	-10000	0	-0.13	75	75
ITSN1	0.035	0.007	-10000	0	0	21	21
PIK3CA	0.031	0.013	-10000	0	0	80	80
SHC1	0.033	0.011	-10000	0	0	52	52
Ephrin B1/EPHB3	0.044	0.015	-10000	0	-10000	0	0
Ephrin B1/EPHB1	0.039	0.025	-10000	0	-0.12	6	6
HRAS/GDP	0.004	0.081	0.17	2	-0.22	40	42
Ephrin B/EPHB1/GRB7	0.067	0.075	-10000	0	-0.12	47	47
Endophilin/SYNJ1	-0.027	0.056	0.19	14	-0.18	2	16
KRAS	0.034	0.009	-10000	0	0	35	35
Ephrin B/EPHB1/Src	0.065	0.077	-10000	0	-0.12	53	53
endothelial cell migration	0.02	0.073	-10000	0	-0.14	63	63
GRB2	0.035	0.007	-10000	0	0	17	17
GRB7	0.036	0.006	-10000	0	0	14	14
PAK1	-0.028	0.061	0.19	18	-10000	0	18
HRAS	0.034	0.009	-10000	0	0	32	32
RRAS	-0.026	0.056	0.2	10	-0.18	9	19
DNM1	0.035	0.008	-10000	0	0	26	26
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.019	0.065	0.18	20	-0.18	11	31
lamellipodium assembly	-0.03	0.04	-10000	0	-0.14	36	36
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.008	0.072	-10000	0	-0.29	14	14
PIK3R1	0.032	0.012	-10000	0	0	63	63
EPHB2	0.034	0.01	-10000	0	0	42	42
EPHB3	0.033	0.011	-10000	0	0	52	52
EPHB1	0.03	0.014	-10000	0	0	95	95
EPHB4	0.025	0.017	-10000	0	0	166	166
mol:GDP	0.019	0.12	0.2	101	-0.24	36	137
Ephrin B/EPHB2	0.051	0.068	-10000	0	-0.11	65	65
Ephrin B/EPHB3	0.05	0.068	-10000	0	-0.11	64	64
JNK cascade	-0.005	0.07	0.23	23	-0.19	4	27
Ephrin B/EPHB1	0.051	0.066	-10000	0	-0.11	54	54
RAP1/GDP	0.028	0.12	0.2	108	-0.22	35	143
EFNB2	0.028	0.015	-10000	0	0	116	116
EFNB3	0.035	0.009	-10000	0	0	29	29
EFNB1	0.037	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.03	0.058	-10000	0	-0.11	52	52
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.036	0.005	-10000	0	0	11	11
CDC42/GTP	0.043	0.083	-10000	0	-0.19	34	34
Rap1/GTP	-0.044	0.052	0.052	8	-0.2	22	30
axon guidance	0.044	0.014	-10000	0	-10000	0	0
MAPK3	-0.009	0.071	0.18	3	-0.27	16	19
MAPK1	-0.009	0.074	0.18	2	-0.28	19	21
Rac1/GDP	-0.008	0.093	0.24	20	-0.24	32	52
actin cytoskeleton reorganization	-0.039	0.06	-10000	0	-0.2	41	41
CDC42/GDP	0.036	0.13	0.22	114	-0.23	35	149
PI3K	0.024	0.076	-10000	0	-0.14	63	63
EFNA5	0.036	0.004	-10000	0	0	6	6
Ephrin B2/EPHB4	0.016	0.047	-10000	0	-0.11	46	46
Ephrin B/EPHB2/Intersectin/N-WASP	0.001	0.06	-10000	0	-0.3	6	6
CDC42	0.035	0.008	-10000	0	0	24	24
RAS family/GTP	-0.052	0.06	-10000	0	-0.24	24	24
PTK2	-0.015	0.08	0.53	9	-0.2	15	24
MAP4K4	-0.005	0.071	0.23	23	-0.19	4	27
SRC	0.036	0.006	-10000	0	0	14	14
KALRN	0.035	0.008	-10000	0	0	23	23
Intersectin/N-WASP	0.032	0.033	-10000	0	-0.14	7	7
neuron projection morphogenesis	0.064	0.17	0.34	123	-0.22	14	137
MAP2K1	-0.001	0.071	0.2	1	-0.27	17	18
WASL	0.024	0.017	-10000	0	0	172	172
Ephrin B1/EPHB1-2/NCK1	0.082	0.038	-10000	0	-0.12	9	9
cell migration	-0.015	0.087	0.22	1	-0.28	20	21
NRAS	0.032	0.012	-10000	0	0	63	63
SYNJ1	-0.027	0.057	0.19	14	-0.18	2	16
PXN	0.036	0.004	-10000	0	0	7	7
TF	-0.022	0.051	0.19	6	-0.18	21	27
HRAS/GTP	0.034	0.079	-10000	0	-0.14	61	61
Ephrin B1/EPHB1-2	0.052	0.035	-10000	0	-0.11	6	6
cell adhesion mediated by integrin	0.019	0.046	0.15	4	-0.27	4	8
RAC1	0.024	0.017	-10000	0	0	173	173
mol:GTP	0.042	0.077	-10000	0	-0.13	62	62
RAC1-CDC42/GTP	-0.03	0.046	-10000	0	-0.2	14	14
RASA1	0.034	0.009	-10000	0	0	32	32
RAC1-CDC42/GDP	0.011	0.095	0.25	18	-0.24	33	51
ruffle organization	0.074	0.17	0.31	141	-0.25	6	147
NCK1	0.035	0.008	-10000	0	0	27	27
receptor internalization	-0.031	0.053	0.18	14	-0.18	2	16
Ephrin B/EPHB2/KALRN	0.064	0.079	-10000	0	-0.12	62	62
ROCK1	-0.01	0.045	0.18	17	-10000	0	17
RAS family/GDP	-0.042	0.063	-10000	0	-0.21	42	42
Rac1/GTP	-0.028	0.045	-10000	0	-0.2	13	13
Ephrin B/EPHB1/Src/Paxillin	0.009	0.065	-10000	0	-0.15	56	56

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.019	0.038	-10000	0	-0.055	93	93
HSPA8	0.036	0.009	-10000	0	0	24	24
SMAD3/SMAD4/ER alpha	0.044	0.087	0.23	8	-0.15	30	38
AKT1	0.029	0.021	-10000	0	-0.029	39	39
GSC	0.002	0.028	0.1	13	-0.064	3	16
NKX2-5	0.033	0.017	0.07	8	-0.06	12	20
muscle cell differentiation	-0.017	0.13	0.3	51	-10000	0	51
SMAD2-3/SMAD4/SP1	0.051	0.14	0.33	5	-0.24	52	57
SMAD4	0.022	0.054	0.14	1	-0.13	32	33
CBFB	0.035	0.006	-10000	0	0	16	16
SAP18	0.034	0.01	-10000	0	0	41	41
Cbp/p300/MSG1	0.011	0.086	-10000	0	-0.13	104	104
SMAD3/SMAD4/VDR	0.045	0.12	-10000	0	-0.2	34	34
MYC	0.029	0.014	-10000	0	-10000	0	0
CDKN2B	-0.21	0.19	-10000	0	-0.57	18	18
AP1	-0.001	0.099	0.21	2	-0.23	50	52
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	-0.011	0.13	-10000	0	-0.36	39	39
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.002	0.081	-10000	0	-0.27	31	31
SP3	0.035	0.016	0.078	14	-0.023	24	38
CREB1	0.036	0.004	-10000	0	0	7	7
FOXH1	0.035	0.016	0.072	10	-0.06	12	22
SMAD3/SMAD4/GR	0.04	0.091	0.26	1	-0.15	38	39
GATA3	0.027	0.018	-10000	0	-10000	0	0
SKI/SIN3/HDAC complex/NCoR1	-0.003	0.091	-10000	0	-0.28	31	31
MEF2C/TIF2	-0.019	0.074	0.3	7	-0.23	15	22
endothelial cell migration	0.19	0.5	1.2	104	-10000	0	104
MAX	0.026	0.043	0.085	85	-0.053	89	174
RBBP7	0.036	0.005	-10000	0	0	8	8
RBBP4	0.033	0.012	-10000	0	0	56	56
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	26	26
NR3C1	0.027	0.043	0.086	84	-0.053	90	174
VDR	0.035	0.007	-10000	0	0	18	18
CDKN1A	-0.11	0.36	0.39	1	-1.1	59	60
KAT2B	-0.003	0.008	-10000	0	-0.024	11	11
SMAD2/SMAD2/SMAD4/FOXH1	0.049	0.077	0.2	2	-0.16	36	38
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	104	104
SMAD3/SMAD4/ATF2	0.041	0.086	0.21	1	-0.15	49	50
SMAD3/SMAD4/ATF3	0.021	0.1	-10000	0	-0.17	81	81
SAP30	0.035	0.007	-10000	0	0	20	20
Cbp/p300/PIAS3	0.041	0.073	-10000	0	-0.094	91	91
JUN	-0.014	0.097	0.18	10	-0.24	45	55
SMAD3/SMAD4/IRF7	0.044	0.09	-10000	0	-0.16	32	32
TFE3	0.016	0.059	0.11	8	-0.095	101	109
COL1A2	-0.045	0.21	-10000	0	-0.64	53	53
mesenchymal cell differentiation	-0.041	0.086	0.15	50	-0.21	1	51
DLX1	0	0	-10000	0	-10000	0	0
TCF3	0.035	0.008	-10000	0	0	28	28
FOS	0.02	0.03	0.12	2	-0.045	46	48
SMAD3/SMAD4/Max	0.041	0.087	0.26	1	-0.16	22	23
Cbp/p300/SNIP1	0.044	0.056	-10000	0	-0.12	9	9
ZBTB17	0.035	0.006	-10000	0	-10000	0	0
LAMC1	-0.033	0.098	0.16	8	-0.29	43	51
TGIF2/HDAC complex/SMAD3/SMAD4	0.04	0.084	0.21	1	-0.14	48	49
IRF7	0.034	0.01	-10000	0	-10000	0	0
ESR1	0.037	0.039	0.12	67	-0.026	59	126
HNF4A	0.035	0.007	-10000	0	0	20	20
MEF2C	-0.028	0.068	0.3	7	-0.23	19	26
SMAD2-3/SMAD4	0.043	0.095	0.24	1	-0.19	31	32
Cbp/p300/Src-1	0.031	0.075	-10000	0	-0.097	100	100
IGHV3OR16-13	0.005	0.056	-10000	0	-0.48	6	6
TGIF2/HDAC complex	0.035	0.008	-10000	0	0	28	28
CREBBP	0.022	0.034	-10000	0	-0.045	101	101
SKIL	0.036	0.006	-10000	0	0	13	13
HDAC1	0.035	0.007	-10000	0	0	21	21
HDAC2	0.032	0.013	-10000	0	0	67	67
SNIP1	0.037	0.007	-10000	0	0	12	12
GCN5L2	0.022	0.034	-10000	0	-0.045	100	100
SMAD3/SMAD4/TFE3	0.031	0.12	0.28	4	-0.22	57	61
MSG1/HSC70	0.009	0.079	-10000	0	-0.14	100	100
SMAD2	0.035	0.017	0.089	2	-0.048	11	13
SMAD3	0.019	0.058	0.14	2	-0.12	43	45
SMAD3/E2F4-5/DP1/p107/SMAD4	0.002	0.073	-10000	0	-0.2	34	34
SMAD2/SMAD2/SMAD4	-0.012	0.07	0.17	10	-0.2	40	50
NCOR1	0.035	0.008	-10000	0	0	26	26
NCOA2	0.036	0.006	-10000	0	0	12	12
NCOA1	0.033	0.011	-10000	0	0	50	50
MYOD/E2A	0.051	0.014	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.059	0.14	0.35	4	-0.23	47	51
IFNB1	-0.005	0.057	0.19	3	-0.2	2	5
SMAD3/SMAD4/MEF2C	0.027	0.092	0.27	3	-0.24	17	20
CITED1	0.026	0.017	-10000	0	0	151	151
SMAD2-3/SMAD4/ARC105	0.042	0.085	0.21	3	-0.17	31	34
RBL1	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.007	0.1	-10000	0	-0.36	23	23
RUNX1-3/PEBPB2	0.066	0.023	-10000	0	-10000	0	0
SMAD7	-0.04	0.18	0.28	3	-0.43	59	62
MYC/MIZ-1	0.028	0.057	-10000	0	-0.14	47	47
SMAD3/SMAD4	-0.08	0.23	-10000	0	-0.47	111	111
IL10	-0.007	0.061	0.19	8	-0.18	3	11
PIASy/HDAC complex	0.028	0.031	0.072	8	-0.031	89	97
PIAS3	0.023	0.029	-10000	0	-0.031	107	107
CDK2	0.021	0.032	-10000	0	-0.03	129	129
IL5	-0.008	0.063	0.19	7	-0.19	3	10
CDK4	0.021	0.031	-10000	0	-0.021	156	156
PIAS4	0.028	0.031	0.072	8	-0.031	89	97
ATF3	0.028	0.016	-10000	0	0	125	125
SMAD3/SMAD4/SP1	0.03	0.14	0.28	6	-0.24	59	65
FOXG1	0.001	0.007	0.023	21	-10000	0	21
FOXO3	-0.009	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	0.068	0.3	7	-0.22	19	26
CEBPB	0.032	0.013	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.025	0.073	0.18	2	-0.14	52	54
MYOD1	0.036	0.004	-10000	0	0	7	7
SMAD3/SMAD4/HNF4	0.04	0.085	0.21	1	-0.14	48	49
SMAD3/SMAD4/GATA3	0.033	0.085	-10000	0	-0.16	23	23
SnoN/SIN3/HDAC complex/NCoR1	0.036	0.006	-10000	0	0	13	13
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.069	0.093	-10000	0	-0.15	20	20
SMAD3/SMAD4/SP1-3	0.047	0.14	0.34	3	-0.23	60	63
MED15	0	0	-10000	0	-10000	0	0
SP1	0.014	0.075	0.12	18	-0.12	107	125
SIN3B	0.035	0.009	-10000	0	0	29	29
SIN3A	0	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.07	0.084	0.25	1	-0.17	27	28
ITGB5	-0.031	0.1	0.2	8	-0.25	41	49
TGIF/SIN3/HDAC complex/CtBP	-0.009	0.096	-10000	0	-0.3	32	32
SMAD3/SMAD4/AR	0.041	0.085	0.21	1	-0.15	47	48
AR	0.035	0.007	-10000	0	0	22	22
negative regulation of cell growth	-0.016	0.12	-10000	0	-0.3	59	59
SMAD3/SMAD4/MYOD	0.042	0.086	0.21	1	-0.15	50	51
E2F5	0.036	0.005	-10000	0	0	8	8
E2F4	0.036	0.006	-10000	0	0	12	12
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.062	0.097	0.24	1	-0.18	31	32
SMAD2-3/SMAD4/FOXO1-3a-4	-0.006	0.097	-10000	0	-0.32	27	27
TFDP1	0.033	0.011	-10000	0	0	53	53
SMAD3/SMAD4/AP1	0.024	0.12	0.26	1	-0.24	48	49
SMAD3/SMAD4/RUNX2	0.041	0.086	0.21	1	-0.15	50	51
TGIF2	0.035	0.008	-10000	0	0	28	28
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	0.036	0.005	-10000	0	0	11	11

×

Sphingosine 1-phosphate (S1P) pathway

Figure S44. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S44. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.034	0.009	-10000	0	0	34	34
SPHK1	0.033	0.011	-10000	0	0	50	50
GNAI2	0.034	0.01	-10000	0	0	43	43
mol:S1P	0.018	0.015	-10000	0	-10000	0	0
GNAO1	0.03	0.014	-10000	0	0	87	87
mol:Sphinganine-1-P	-0.012	0.032	0.092	42	-10000	0	42
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.028	0.046	-10000	0	-0.16	4	4
GNAI3	0.036	0.006	-10000	0	0	15	15
G12/G13	0.025	0.047	-10000	0	-0.14	28	28
S1PR3	0	0	-10000	0	-10000	0	0
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	0.033	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	263	263
S1P/S1P5/G12	0.016	0.037	-10000	0	-0.16	4	4
S1P/S1P3/Gq	0.025	0.042	-10000	0	-0.26	7	7
S1P/S1P4/Gi	-0.003	0.11	0.13	7	-0.22	74	81
GNAQ	0.034	0.009	-10000	0	0	31	31
GNAZ	0.031	0.013	-10000	0	0	81	81
GNA14	0.034	0.009	-10000	0	0	30	30
GNA15	0.033	0.012	-10000	0	0	57	57
GNA12	0.023	0.018	-10000	0	0	193	193
GNA13	0.035	0.007	-10000	0	0	19	19
GNA11	0.033	0.011	-10000	0	0	54	54
ABCC1	0.035	0.007	-10000	0	0	19	19

×

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	0.099	-10000	0	-0.25	27	27
mol:DAG	-0.012	0.09	0.18	4	-0.25	27	31
PLCG1	-0.013	0.092	0.18	4	-0.25	27	31
YES1	-0.016	0.084	-10000	0	-0.18	85	85
FZD3	0.029	0.015	-10000	0	0	110	110
FZD6	0.027	0.016	-10000	0	0	130	130
G protein	0.003	0.1	0.2	23	-0.27	25	48
MAP3K7	-0.036	0.074	0.14	6	-0.23	31	37
mol:Ca2+	-0.012	0.088	0.18	4	-0.24	27	31
mol:IP3	-0.012	0.09	0.18	4	-0.25	27	31
NLK	-0.039	0.25	-10000	0	-0.78	52	52
GNB1	0.035	0.007	-10000	0	0	20	20
CAMK2A	-0.031	0.078	0.16	5	-0.24	27	32
MAP3K7IP1	0.034	0.009	-10000	0	0	35	35
Noncanonical Wnts/FZD	-0.006	0.089	-10000	0	-0.17	89	89
CSNK1A1	0.036	0.006	-10000	0	0	14	14
GNAS	-0.014	0.08	-10000	0	-0.17	83	83
GO:0007205	-0.02	0.085	0.18	4	-0.25	27	31
WNT6	0.037	0.002	-10000	0	0	1	1
WNT4	0.035	0.007	-10000	0	0	18	18
NFAT1/CK1 alpha	-0.005	0.098	0.22	5	-0.26	27	32
GNG2	0	0	-10000	0	-10000	0	0
WNT5A	0.029	0.015	-10000	0	0	99	99
WNT11	0.036	0.006	-10000	0	0	14	14
CDC42	-0.025	0.082	0.17	5	-0.27	21	26

×

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	-0.013	0.19	-10000	0	-0.8	24	24
regulation of axonogenesis	0.003	0.064	0.21	36	-10000	0	36
myoblast fusion	-0.015	0.093	0.35	27	-10000	0	27
mol:GTP	0.015	0.065	-10000	0	-0.18	48	48
regulation of calcium-dependent cell-cell adhesion	-0.026	0.073	0.15	62	-0.15	1	63
ARF1/GTP	0.035	0.061	-10000	0	-0.14	50	50
mol:GM1	0.003	0.047	-10000	0	-0.13	49	49
mol:Choline	-0.015	0.041	0.085	3	-0.13	40	43
lamellipodium assembly	-0.009	0.1	-10000	0	-0.37	33	33
MAPK3	0.012	0.081	0.14	37	-0.23	37	74
ARF6/GTP/NME1/Tiam1	0.027	0.074	0.15	1	-0.15	62	63
ARF1	0.035	0.008	-10000	0	0	24	24
ARF6/GDP	0.015	0.093	-10000	0	-0.35	27	27
ARF1/GDP	0.013	0.1	-10000	0	-0.28	45	45
ARF6	0.039	0.042	-10000	0	-0.13	25	25
RAB11A	0.035	0.007	-10000	0	0	18	18
TIAM1	0.029	0.022	-10000	0	-0.044	32	32
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.012	0.082	0.14	36	-0.24	36	72
actin filament bundle formation	-0.019	0.11	0.28	49	-10000	0	49
KALRN	0.006	0.069	-10000	0	-0.26	28	28
RAB11FIP3/RAB11A	0.047	0.034	-10000	0	-0.16	12	12
RhoA/GDP	0.02	0.11	-10000	0	-0.28	49	49
NME1	-0.001	0.008	-10000	0	-0.03	25	25
Rac1/GDP	0.013	0.089	-10000	0	-0.28	34	34
substrate adhesion-dependent cell spreading	0.015	0.065	-10000	0	-0.18	48	48
cortical actin cytoskeleton organization	-0.009	0.1	-10000	0	-0.37	33	33
RAC1	0.024	0.017	-10000	0	0	173	173
liver development	0.015	0.065	-10000	0	-0.18	48	48
ARF6/GTP	0.015	0.065	-10000	0	-0.18	48	48
RhoA/GTP	0.034	0.063	-10000	0	-0.14	52	52
mol:GDP	-0.005	0.1	0.17	2	-0.3	46	48
ARF6/GTP/RAB11FIP3/RAB11A	0.051	0.068	-10000	0	-0.13	58	58
RHOA	0.035	0.007	-10000	0	0	18	18
PLD1	0.012	0.051	-10000	0	-0.14	45	45
RAB11FIP3	0.036	0.006	-10000	0	0	15	15
tube morphogenesis	-0.009	0.1	-10000	0	-0.37	33	33
ruffle organization	-0.003	0.064	-10000	0	-0.21	36	36
regulation of epithelial cell migration	0.015	0.065	-10000	0	-0.18	48	48
PLD2	0.012	0.052	-10000	0	-0.14	47	47
PIP5K1A	-0.003	0.064	-10000	0	-0.21	36	36
mol:Phosphatidic acid	-0.015	0.041	0.085	3	-0.13	40	43
Rac1/GTP	-0.009	0.1	-10000	0	-0.37	33	33

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.042	0.01	-10000	0	-0.042	1	1
NFATC2	0.014	0.15	0.27	6	-0.35	43	49
NFATC3	0.017	0.13	0.26	25	-0.24	71	96
CD40LG	-0.016	0.33	0.48	44	-0.71	64	108
ITCH	0.035	0.046	0.19	8	-10000	0	8
CBLB	0.036	0.048	0.19	11	-10000	0	11
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.051	0.26	0.38	13	-0.62	56	69
JUNB	0.031	0.014	-10000	0	0	83	83
CaM/Ca2+/Calcineurin A alpha-beta B1	0.033	0.027	-10000	0	-0.13	6	6
T cell anergy	0.016	0.067	0.26	10	-0.25	1	11
TLE4	0.01	0.11	-10000	0	-0.31	22	22
Jun/NFAT1-c-4/p21SNFT	-0.017	0.33	0.44	5	-0.73	70	75
AP-1/NFAT1-c-4	-0.033	0.35	-10000	0	-0.79	64	64
IKZF1	0.006	0.099	0.17	6	-0.24	39	45
T-helper 2 cell differentiation	-0.085	0.23	-10000	0	-0.62	45	45
AP-1/NFAT1	0.017	0.14	0.28	17	-0.29	45	62
CALM1	0.046	0.024	0.13	2	-10000	0	2
EGR2	-0.08	0.41	0.51	10	-0.98	74	84
EGR3	-0.059	0.42	0.49	16	-0.99	70	86
NFAT1/FOXP3	0.038	0.12	0.25	4	-0.26	36	40
EGR1	0.029	0.015	0.07	1	-10000	0	1
JUN	0.032	0.041	0.11	34	-0.054	9	43
EGR4	0.037	0.004	0.07	1	-10000	0	1
mol:Ca2+	0.005	0.003	-10000	0	-10000	0	0
GBP3	0.006	0.099	0.17	6	-0.24	39	45
FOSL1	0.033	0.011	-10000	0	0	55	55
NFAT1-c-4/MAF/IRF4	0.009	0.33	-10000	0	-0.72	74	74
DGKA	0.011	0.1	0.21	1	-0.28	27	28
CREM	0.026	0.016	-10000	0	0	142	142
NFAT1-c-4/PPARG	-0.009	0.33	-10000	0	-0.73	73	73
CTLA4	0.009	0.092	0.18	1	-0.26	22	23
NFAT1-c-4 (dimer)/EGR1	-0.03	0.34	-10000	0	-0.77	74	74
NFAT1-c-4 (dimer)/EGR4	-0.001	0.33	-10000	0	-0.74	73	73
FOS	0.023	0.038	0.11	19	-0.05	7	26
IFNG	-0.009	0.13	-10000	0	-0.45	10	10
T cell activation	-0.013	0.21	-10000	0	-0.58	20	20
MAF	0.034	0.009	-10000	0	0	35	35
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.008	0.28	0.6	72	-0.45	22	94
TNF	-0.04	0.31	0.4	9	-0.7	74	83
FASLG	-0.1	0.46	-10000	0	-1.1	74	74
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	0.008	0.12	0.42	1	-0.37	23	24
NFAT1-c-4/ICER1	-0.033	0.32	-10000	0	-0.73	73	73
GATA3	0.027	0.018	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.004	0.14	-10000	0	-0.44	10	10
IL2RA	-0.06	0.25	0.35	6	-0.6	61	67
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.007	0.11	-10000	0	-0.36	24	24
E2F1	0.037	0.051	0.11	2	-0.25	13	15
PPARG	0.035	0.008	-10000	0	-10000	0	0
SLC3A2	0.008	0.12	0.24	2	-0.38	26	28
IRF4	0.037	0.002	-10000	0	0	1	1
PTGS2	-0.071	0.28	0.43	3	-0.71	63	66
CSF2	-0.016	0.33	0.48	44	-0.71	65	109
JunB/Fra1/NFAT1-c-4	-0.014	0.31	-10000	0	-0.72	70	70
IL4	-0.089	0.24	-10000	0	-0.64	45	45
IL5	-0.016	0.33	0.48	44	-0.71	65	109
IL2	-0.013	0.22	-10000	0	-0.59	19	19
IL3	0.007	0.088	-10000	0	-0.58	7	7
RNF128	0.014	0.022	0.17	1	-10000	0	1
NFATC1	-0.008	0.28	0.45	22	-0.6	72	94
CDK4	-0.011	0.27	0.52	35	-1	14	49
PTPRK	-0.001	0.14	-10000	0	-0.43	34	34
IL8	-0.1	0.29	0.46	7	-0.75	62	69
POU2F1	0.039	0.008	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	-0.019	0.11	0.15	11	-0.36	29	40
adherens junction organization	-0.001	0.076	0.16	3	-0.31	19	22
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.026	0.11	0.19	49	-0.3	21	70
FMN1	0.008	0.063	0.15	4	-0.27	15	19
mol:IP3	-0.008	0.079	0.14	5	-0.25	32	37
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.013	0.067	0.16	4	-0.28	15	19
CTNNB1	0.035	0.006	-10000	0	0	15	15
AKT1	-0.006	0.088	0.14	2	-0.28	32	34
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.027	0.067	-10000	0	-0.39	6	6
CTNND1	0.035	0.009	-10000	0	0	32	32
mol:PI-4-5-P2	0.003	0.067	0.15	7	-0.27	17	24
VASP	0.002	0.062	0.15	3	-0.27	15	18
ZYX	0.006	0.057	0.14	4	-0.32	9	13
JUB	0.008	0.063	0.15	4	-0.27	15	19
EGFR(dimer)	0.001	0.065	-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	0.02	0.093	-10000	0	-0.29	25	25
PIK3CA	0.03	0.015	-10000	0	-0.002	84	84
PI3K	0.02	0.095	-10000	0	-0.29	25	25
FYN	-0.042	0.13	0.25	1	-0.31	76	77
mol:Ca2+	-0.008	0.078	0.14	5	-0.24	32	37
JUP	0.033	0.011	0.056	1	0	51	52
PIK3R1	0.031	0.015	-10000	0	-0.004	72	72
mol:DAG	-0.008	0.079	0.14	5	-0.25	32	37
CDH1	0.034	0.01	-10000	0	0	38	38
RhoA/GDP	0.062	0.13	0.19	99	-0.29	22	121
establishment of polarity of embryonic epithelium	0.002	0.062	0.15	4	-0.27	15	19
SRC	0.036	0.006	-10000	0	0	14	14
RAC1	0.024	0.017	-10000	0	0	173	173
RHOA	0.035	0.007	-10000	0	0	18	18
EGFR	0.009	0.016	-10000	0	0	381	381
CASR	-0.024	0.075	0.14	18	-0.27	25	43
RhoA/GTP	0.009	0.086	0.15	1	-0.26	27	28
AKT2	-0.005	0.08	0.14	2	-0.28	25	27
actin cable formation	-0.002	0.061	0.15	3	-0.26	16	19
apoptosis	0.01	0.098	0.33	29	-0.17	12	41
CTNNA1	0.035	0.008	-10000	0	-0.001	21	21
mol:GDP	-0.021	0.074	0.19	4	-0.3	21	25
PIP5K1A	0.003	0.067	0.15	7	-0.27	17	24
PLCG1	-0.008	0.081	0.14	5	-0.26	32	37
Rac1/GTP	-0.004	0.069	-10000	0	-0.32	13	13
homophilic cell adhesion	-0.001	0.003	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.033	0.01	-10000	0	0	45	45
VLDLR	0.027	0.016	-10000	0	0	135	135
LRPAP1	0.035	0.007	-10000	0	0	18	18
NUDC	0.035	0.008	-10000	0	0	27	27
RELN/LRP8	0.039	0.044	-10000	0	-0.13	11	11
CaM/Ca2+	0.021	0.026	-10000	0	-0.13	13	13
KATNA1	0.033	0.01	-10000	0	0	44	44
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	0.037	0.1	0.19	139	-0.21	6	145
IQGAP1/CaM	0.031	0.058	-10000	0	-0.15	44	44
DAB1	0.036	0.005	-10000	0	0	9	9
IQGAP1	0.033	0.011	-10000	0	0	51	51
PLA2G7	0.033	0.011	-10000	0	0	53	53
CALM1	0.033	0.011	-10000	0	0	54	54
DYNLT1	0.033	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	24	24
LIS1/Poliovirus Protein 3A	-0.023	0.028	-10000	0	-0.14	24	24
CDK5R2	0.035	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	-0.12	19	19
YWHAE	0.035	0.008	-10000	0	0	27	27
NDEL1/14-3-3 E	0.064	0.17	0.32	136	-0.27	17	153
MAP1B	-0.014	0.067	-10000	0	-0.2	51	51
RAC1	-0.003	0.051	-10000	0	-0.26	12	12
p35/CDK5	-0.025	0.056	0.2	7	-0.21	12	19
RELN	0.023	0.018	-10000	0	0	188	188
PAFAH/LIS1	0.022	0.039	-10000	0	-0.15	21	21
LIS1/CLIP170	-0.023	0.028	-10000	0	-0.14	24	24
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.034	0.078	0.13	18	-0.27	26	44
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.014	0.087	0.17	1	-0.23	52	53
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	0.056	0.16	0.31	123	-0.27	15	138
LIS1/IQGAP1	0.014	0.058	-10000	0	-0.15	50	50
RHOA	-0.005	0.065	-10000	0	-0.33	13	13
PAFAH1B1	-0.021	0.007	-10000	0	-10000	0	0
PAFAH1B3	0.031	0.013	-10000	0	0	76	76
PAFAH1B2	0.036	0.004	-10000	0	0	7	7
MAP1B/LIS1/Dynein heavy chain	0.007	0.078	-10000	0	-0.2	54	54
NDEL1/Katanin 60/Dynein heavy chain	0.082	0.15	0.33	112	-0.26	22	134
LRP8	0.034	0.009	-10000	0	0	35	35
NDEL1/Katanin 60	0.056	0.16	0.31	126	-0.27	18	144
P39/CDK5	-0.025	0.056	0.2	7	-0.21	12	19
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.021	0.052	-10000	0	-0.19	26	26
CDK5	-0.014	0.045	0.19	8	-0.22	6	14
PPP2R5D	0.036	0.004	-10000	0	0	5	5
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.019	0.023	-10000	0	-0.12	24	24
CSNK2A1	0.034	0.009	-10000	0	0	31	31
RELN/VLDLR/DAB1/LIS1	0.033	0.059	0.18	3	-0.13	33	36
RELN/VLDLR	0.044	0.06	-10000	0	-0.12	26	26
CDC42	-0.002	0.045	-10000	0	-0.21	12	12

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.028	0.041	-10000	0	-0.14	18	18
VLDLR	0.027	0.016	-10000	0	0	135	135
CRKL	0.035	0.009	-10000	0	0	29	29
LRPAP1	0.035	0.007	-10000	0	0	18	18
FYN	0.03	0.014	-10000	0	0	90	90
ITGA3	0.033	0.011	-10000	0	0	56	56
RELN/VLDLR/Fyn	0.018	0.06	-10000	0	-0.13	51	51
MAPK8IP1/MKK7/MAP3K11/JNK1	0.068	0.06	-10000	0	-0.11	4	4
AKT1	-0.014	0.069	-10000	0	-0.2	49	49
MAP2K7	0.035	0.008	-10000	0	0	24	24
RAPGEF1	0.035	0.007	-10000	0	0	19	19
DAB1	0.036	0.005	-10000	0	0	9	9
RELN/LRP8/DAB1	0.041	0.036	-10000	0	-0.11	3	3
LRPAP1/LRP8	0.045	0.036	-10000	0	-0.15	14	14
RELN/LRP8/DAB1/Fyn	0.041	0.059	-10000	0	-0.12	33	33
DAB1/alpha3/beta1 Integrin	0.029	0.058	-10000	0	-0.19	1	1
long-term memory	0.042	0.064	-10000	0	-0.12	31	31
DAB1/LIS1	0.048	0.072	-10000	0	-0.13	30	30
DAB1/CRLK/C3G	0.038	0.058	-10000	0	-0.12	23	23
PIK3CA	0.031	0.013	-10000	0	0	80	80
DAB1/NCK2	0.049	0.072	-10000	0	-0.13	28	28
ARHGEF2	0.035	0.007	-10000	0	0	20	20
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.035	0.006	-10000	0	0	16	16
CDK5R1	0.035	0.008	-10000	0	0	24	24
RELN	0.023	0.018	-10000	0	0	188	188
PIK3R1	0.032	0.012	-10000	0	0	63	63
RELN/LRP8/Fyn	0.029	0.056	-10000	0	-0.13	34	34
GRIN2A/RELN/LRP8/DAB1/Fyn	0.051	0.071	-10000	0	-0.12	33	33
MAPK8	0.027	0.016	-10000	0	0	138	138
RELN/VLDLR/DAB1	0.03	0.044	-10000	0	-0.11	19	19
ITGB1	0.027	0.016	-10000	0	0	138	138
MAP1B	0.023	0.083	0.16	107	-0.21	3	110
RELN/LRP8	0.039	0.044	-10000	0	-0.13	11	11
GRIN2B/RELN/LRP8/DAB1/Fyn	0.051	0.07	-10000	0	-0.12	31	31
PI3K	0.019	0.075	-10000	0	-0.16	73	73
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.034	0.027	-10000	0	-0.14	1	1
RAP1A	0.032	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	0.007	-10000	0	0	22	22
NCK2	0.035	0.007	-10000	0	0	17	17
neuron differentiation	0.009	0.064	-10000	0	-0.22	14	14
neuron adhesion	0.033	0.11	0.25	42	-10000	0	42
LRP8	0.034	0.009	-10000	0	0	35	35
GSK3B	-0.009	0.079	0.18	1	-0.31	17	18
RELN/VLDLR/DAB1/Fyn	0.031	0.064	-10000	0	-0.11	51	51
MAP3K11	0.036	0.005	-10000	0	0	10	10
RELN/VLDLR/DAB1/P13K	-0.008	0.074	-10000	0	-0.19	55	55
CDK5	0.023	0.018	-10000	0	0	192	192
MAPT	-0.013	0.067	0.72	1	-10000	0	1
neuron migration	0	0.12	0.2	74	-0.28	32	106
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.009	0.064	-10000	0	-0.22	14	14
RELN/VLDLR	0.044	0.06	-10000	0	-0.12	26	26

×

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	0.009	-10000	0	0	29	29
Rac1/GDP	0.024	0.021	-10000	0	-0.025	10	10
DOCK1	0.024	0.017	-10000	0	0	175	175
ITGA4	0.036	0.006	-10000	0	0	13	13
RAC1	0.024	0.017	-10000	0	0	173	173
alpha4/beta7 Integrin	0.052	0.011	-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	0.034	-10000	0	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.052	0.017	-10000	0	-10000	0	0
lamellipodium assembly	-0.046	0.14	-10000	0	-0.36	73	73
PIK3CA	0.031	0.013	-10000	0	0	80	80
PI3K	0.019	0.075	-10000	0	-0.16	73	73
ARF6	0.035	0.008	-10000	0	0	27	27
TLN1	0.029	0.015	-10000	0	0	102	102
PXN	-0.021	0.01	0.092	3	-10000	0	3
PIK3R1	0.032	0.012	-10000	0	0	63	63
ARF6/GTP	0.049	0.048	-10000	0	-0.11	1	1
cell adhesion	0.049	0.047	-10000	0	-0.11	13	13
CRKL/CBL	0.051	0.014	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.039	0.026	-10000	0	-10000	0	0
ITGB1	0.027	0.016	-10000	0	0	138	138
ITGB7	0.036	0.005	-10000	0	0	11	11
ARF6/GDP	0.035	0.015	-10000	0	-0.025	14	14
alpha4/beta1 Integrin/Paxillin/VCAM1	0.016	0.079	-10000	0	-0.11	116	116
p130Cas/Crk/Dock1	0.028	0.035	-10000	0	-0.11	17	17
VCAM1	0.022	0.018	-10000	0	0	196	196
alpha4/beta1 Integrin/Paxillin/Talin	0.051	0.048	-10000	0	-0.12	13	13
alpha4/beta1 Integrin/Paxillin/GIT1	0.059	0.04	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.057	0.039	-10000	0	-10000	0	0
CBL	0.036	0.004	-10000	0	0	7	7
PRKACA	0.035	0.008	-10000	0	0	25	25
GIT1	0.036	0.003	-10000	0	0	4	4
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.051	0.048	-10000	0	-0.12	13	13
Rac1/GTP	-0.052	0.16	-10000	0	-0.4	73	73

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.063	0.064	-9999	-0.12	12	12
SMAD6-7/SMURF1	0.044	0.038	-9999	-0.12	2	2
NOG	0	0	-9999	-10000	0	0
SMAD9	-0.024	0.15	-9999	-0.44	54	54
SMAD4	0.032	0.012	-9999	0	58	58
SMAD5	-0.029	0.098	-9999	-0.3	45	45
BMP7/USAG1	0.033	0.027	-9999	-10000	0	0
SMAD5/SKI	-0.021	0.11	-9999	-0.3	45	45
SMAD1	-0.031	0.15	-9999	-0.4	50	50
BMP2	0.029	0.015	-9999	0	107	107
SMAD1/SMAD1/SMAD4	-0.01	0.13	-9999	-0.36	42	42
BMPR1A	0.025	0.017	-9999	0	167	167
BMPR1B	0.036	0.006	-9999	0	14	14
BMPR1A-1B/BAMBI	0.02	0.06	-9999	-0.13	50	50
AHSG	0.035	0.009	-9999	0	29	29
CER1	0.031	0.013	-9999	0	71	71
BMP2-4/CER1	0.039	0.055	-9999	-0.12	35	35
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.01	0.078	-9999	-0.21	42	42
BMP2-4 (homodimer)	0.029	0.051	-9999	-0.14	35	35
RGMB	0	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.058	0.052	-9999	-0.12	12	12
RGMA	0	0	-9999	-10000	0	0
SMURF1	0.025	0.017	-9999	0	167	167
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.021	0.07	-9999	-0.17	58	58
BMP2-4/USAG1	0.033	0.046	-9999	-0.12	16	16
SMAD6/SMURF1/SMAD5	-0.012	0.09	-9999	-0.29	34	34
SOSTDC1	0.023	0.018	-9999	0	184	184
BMP7/BMPR2/BMPR1A-1B	0.058	0.053	-9999	-0.12	14	14
SKI	0.037	0	-9999	-10000	0	0
BMP6 (homodimer)	0.035	0.008	-9999	0	24	24
HFE2	0	0	-9999	-10000	0	0
ZFYVE16	0.034	0.009	-9999	0	35	35
MAP3K7	0.034	0.01	-9999	0	41	41
BMP2-4/CHRD	0.043	0.054	-9999	-0.12	34	34
SMAD5/SMAD5/SMAD4	-0.022	0.11	-9999	-0.31	43	43
MAPK1	0.033	0.01	-9999	0	45	45
TAK1/TAB family	0.019	0.083	-9999	-0.2	19	19
BMP7 (homodimer)	0.034	0.01	-9999	0	39	39
NUP214	0.035	0.007	-9999	0	18	18
BMP6/FETUA	0.049	0.016	-9999	-10000	0	0
SMAD1/SKI	-0.015	0.15	-9999	-0.38	52	52
SMAD6	0.036	0.005	-9999	0	11	11
CTDSP2	0.033	0.012	-9999	0	57	57
BMP2-4/FETUA	0.042	0.055	-9999	-0.12	35	35
MAP3K7IP1	0.034	0.009	-9999	0	35	35
GREM1	0.032	0.012	-9999	0	64	64
BMPR2 (homodimer)	0.036	0.006	-9999	0	12	12
GADD34/PP1CA	0.052	0.053	-9999	-0.13	31	31
BMPR1A-1B (homodimer)	0.034	0.032	-9999	-0.14	6	6
CHRDL1	0	0	-9999	-10000	0	0
ENDOFIN/SMAD1	-0.018	0.15	-9999	-0.39	53	53
SMAD6-7/SMURF1/SMAD1	0.004	0.14	-9999	-0.38	42	42
SMAD6/SMURF1	0.025	0.017	-9999	0	167	167
BAMBI	0.018	0.018	-9999	0	255	255
SMURF2	0.035	0.007	-9999	0	20	20
BMP2-4/CHRDL1	0.028	0.043	-9999	-0.11	35	35
BMP2-4/GREM1	0.039	0.054	-9999	-0.12	33	33
SMAD7	0.033	0.01	-9999	0	44	44
SMAD8A/SMAD8A/SMAD4	-0.012	0.15	-9999	-0.41	58	58
SMAD1/SMAD6	-0.015	0.14	-9999	-0.38	43	43
TAK1/SMAD6	0.032	0.034	-9999	-0.14	8	8
BMP7	0.034	0.01	-9999	0	39	39
BMP6	0.035	0.008	-9999	0	24	24
MAP3K7IP2	0.033	0.011	-9999	0	46	46
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.003	0.055	-9999	-0.22	16	16
PPM1A	0.034	0.009	-9999	0	30	30
SMAD1/SMURF2	-0.017	0.15	-9999	-0.39	51	51
SMAD7/SMURF1	0.033	0.029	-9999	-0.14	2	2
CTDSPL	0.036	0.006	-9999	0	12	12
PPP1CA	0.035	0.007	-9999	0	20	20
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0.035	0.006	-9999	0	16	16
PPP1R15A	0.033	0.011	-9999	0	55	55
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.016	0.072	-9999	-0.17	55	55
CHRD	0.035	0.007	-9999	0	22	22
BMPR2	0.036	0.006	-9999	0	12	12
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.02	0.071	-9999	-0.18	53	53
BMP4	0.033	0.011	-9999	0	49	49
FST	0.033	0.011	-9999	0	48	48
BMP2-4/NOG	0.028	0.043	-9999	-0.11	35	35
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.05	0.061	-9999	-0.11	10	10

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.023	0.053	0.17	14	-0.22	9	23
DAPP1	-0.027	0.12	-10000	0	-0.3	66	66
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.048	0.19	0.24	3	-0.45	68	71
mol:DAG	-0.015	0.087	0.2	13	-0.2	47	60
HRAS	0.034	0.02	0.068	1	-0.015	59	60
RAP1A	0.038	0.013	0.063	4	-0.017	20	24
ARF5/GDP	-0.002	0.095	-10000	0	-0.3	33	33
PLCG2	0.032	0.012	-10000	0	0	63	63
PLCG1	0.035	0.007	-10000	0	0	19	19
ARF5	0.024	0.017	-10000	0	0	175	175
mol:GTP	-0.025	0.052	0.16	16	-0.2	9	25
ARF1/GTP	-0.02	0.045	0.12	14	-0.2	11	25
RHOA	0.035	0.007	-10000	0	0	18	18
YES1	0.034	0.01	-10000	0	0	41	41
RAP1A/GTP	-0.025	0.051	0.16	15	-0.19	9	24
ADAP1	-0.026	0.046	0.14	13	-0.19	9	22
ARAP3	-0.025	0.051	0.16	16	-0.19	9	25
INPPL1	0.036	0.006	-10000	0	0	12	12
PREX1	0	0	-10000	0	-10000	0	0
ARHGEF6	0.033	0.011	-10000	0	0	48	48
ARHGEF7	0.032	0.012	-10000	0	0	59	59
ARF1	0.035	0.008	-10000	0	0	24	24
NRAS	0.034	0.018	0.068	1	-0.005	75	76
FYN	0.03	0.014	-10000	0	0	90	90
ARF6	0.035	0.008	-10000	0	0	27	27
FGR	0.033	0.011	-10000	0	0	54	54
mol:Ca2+	0.003	0.058	0.15	29	-0.12	17	46
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.033	0.011	-10000	0	0	46	46
ZAP70	0.036	0.002	-10000	0	0	2	2
mol:IP3	-0.009	0.068	0.18	26	-0.16	19	45
LYN	0.031	0.013	-10000	0	0	74	74
ARF1/GDP	0.007	0.11	-10000	0	-0.33	36	36
RhoA/GDP	0.023	0.089	0.18	12	-0.21	30	42
PDK1/Src/Hsp90	0.047	0.01	-10000	0	-10000	0	0
BLNK	0.019	0.018	-10000	0	0	243	243
actin cytoskeleton reorganization	0.007	0.1	0.2	21	-0.29	25	46
SRC	0.036	0.006	-10000	0	0	14	14
PLEKHA2	-0.012	0.024	0.085	29	-10000	0	29
RAC1	0.024	0.017	-10000	0	0	173	173
PTEN	0.026	0.022	-10000	0	-0.035	16	16
HSP90AA1	0	0	-10000	0	-10000	0	0
ARF6/GTP	-0.028	0.052	0.16	15	-0.2	9	24
RhoA/GTP	-0.028	0.058	0.18	17	-0.21	10	27
Src family/SYK family/BLNK-LAT	-0.053	0.16	-10000	0	-0.35	86	86
BLK	0.035	0.007	-10000	0	0	17	17
PDPK1	0.036	0.004	-10000	0	0	7	7
CYTH1	-0.026	0.046	0.14	13	-0.19	9	22
HCK	0.027	0.016	-10000	0	0	128	128
CYTH3	-0.026	0.046	0.14	13	-0.19	9	22
CYTH2	-0.026	0.046	0.14	13	-0.19	9	22
KRAS	0.034	0.021	0.075	2	-0.032	31	33
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.003	0.031	0.21	3	-0.16	1	4
SGK1	0	0.03	0.21	2	-0.15	2	4
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.008	0.11	0.14	3	-0.33	37	40
SOS1	0	0	-10000	0	-10000	0	0
SYK	0.031	0.013	-10000	0	0	76	76
ARF6/GDP	-0.028	0.066	0.18	13	-0.22	26	39
mol:PI-3-4-5-P3	-0.026	0.049	0.15	13	-0.2	9	22
ARAP3/RAP1A/GTP	-0.025	0.051	0.16	15	-0.2	9	24
VAV1	0.034	0.009	-10000	0	0	35	35
mol:PI-3-4-P2	-0.011	0.002	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.062	0.092	0.21	102	-0.14	42	144
PLEKHA1	-0.008	0.022	0.085	23	-10000	0	23
Rac1/GDP	-0.002	0.098	-10000	0	-0.3	34	34
LAT	0.036	0.005	-10000	0	0	10	10
Rac1/GTP	-0.005	0.15	-10000	0	-0.42	41	41
ITK	-0.029	0.049	0.15	14	-0.19	9	23
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.026	0.11	0.23	11	-0.27	54	65
LCK	0.035	0.007	-10000	0	0	17	17
BTK	-0.027	0.052	0.15	17	-0.19	9	26

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.041	0.087	0.22	29	-0.18	17	46
TBX21	0.067	0.2	0.57	6	-0.58	2	8
B2M	0.035	0.008	-10000	0	0	27	27
TYK2	0.036	0.039	0.12	13	-0.054	9	22
IL12RB1	0.037	0.04	0.12	16	-0.054	12	28
GADD45B	0.058	0.29	0.54	13	-0.99	24	37
IL12RB2	0.04	0.04	0.12	19	-0.052	22	41
GADD45G	0.089	0.18	0.52	11	-0.54	3	14
natural killer cell activation	0.012	0.024	0.055	73	-0.036	9	82
RELB	0.034	0.009	-10000	0	0	32	32
RELA	0.036	0.005	-10000	0	0	9	9
IL18	0.034	0.022	0.088	2	-0.043	17	19
IL2RA	0.024	0.017	-10000	0	0	172	172
IFNG	0.034	0.009	-10000	0	0	30	30
STAT3 (dimer)	0.072	0.22	0.45	26	-0.54	21	47
HLA-DRB5	-0.001	0.009	-10000	0	-0.023	42	42
FASLG	0.071	0.2	0.53	10	-0.54	5	15
NF kappa B2 p52/RelB	0.05	0.18	0.43	11	-0.46	15	26
CD4	0.025	0.026	-10000	0	-0.017	127	127
SOCS1	0.036	0.005	-10000	0	0	8	8
EntrezGene:6955	-0.001	0.01	-10000	0	-0.025	56	56
CD3D	0.025	0.028	-10000	0	-0.025	108	108
CD3E	0.028	0.027	-10000	0	-0.035	76	76
CD3G	0.027	0.028	-10000	0	-0.042	67	67
IL12Rbeta2/JAK2	0.055	0.059	0.18	18	-10000	0	18
CCL3	0.07	0.2	0.45	26	-0.47	15	41
CCL4	0.039	0.33	0.56	16	-1	31	47
HLA-A	0.036	0.006	-10000	0	0	13	13
IL18/IL18R	0.094	0.061	0.21	26	-0.11	15	41
NOS2	0.072	0.19	0.43	32	-0.42	17	49
IL12/IL12R/TYK2/JAK2/SPHK2	0.038	0.086	0.22	26	-0.18	18	44
IL1R1	0.069	0.2	0.58	8	-0.56	3	11
IL4	0.004	0.048	-10000	0	-0.073	81	81
JAK2	0.033	0.038	0.11	12	-0.051	23	35
EntrezGene:6957	-0.001	0.009	-10000	0	-0.023	42	42
TCR/CD3/MHC I/CD8	0.006	0.044	0.11	1	-0.17	15	16
RAB7A	0.09	0.2	0.44	28	-0.54	20	48
lysosomal transport	0.09	0.2	0.44	29	-0.51	20	49
FOS	-0.11	0.48	0.49	12	-1.1	94	106
STAT4 (dimer)	0.084	0.2	0.45	31	-0.47	18	49
STAT5A (dimer)	0.077	0.19	0.43	10	-0.47	15	25
GZMA	0.067	0.2	0.55	12	-0.52	7	19
GZMB	0.066	0.2	0.56	12	-0.52	9	21
HLX	0	0	-10000	0	-10000	0	0
LCK	0.061	0.2	0.46	24	-0.49	15	39
TCR/CD3/MHC II/CD4	-0.023	0.12	0.16	22	-0.25	80	102
IL2/IL2R	0.063	0.044	-10000	0	-10000	0	0
MAPK14	0.092	0.23	0.5	19	-0.63	20	39
CCR5	0.075	0.17	0.39	36	-0.39	16	52
IL1B	0.029	0.037	0.11	8	-0.053	11	19
STAT6	0.052	0.098	0.31	13	-0.4	3	16
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	158	158
IL12B	0.04	0.04	0.12	19	-0.055	11	30
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	-0.04	0.087	0.18	17	-0.22	29	46
IL2RB	0.033	0.011	-10000	0	0	53	53
proteasomal ubiquitin-dependent protein catabolic process	0.085	0.2	0.44	34	-0.44	18	52
IL2RG	0.035	0.008	-10000	0	0	24	24
IL12	0.061	0.06	0.18	20	-10000	0	20
STAT5A	0.036	0.004	-10000	0	0	5	5
CD247	-0.001	0.009	-10000	0	-0.023	42	42
IL2	0.036	0.005	-10000	0	0	10	10
SPHK2	0.034	0.009	-10000	0	0	34	34
FRAP1	0.035	0.007	-10000	0	0	17	17
IL12A	0.038	0.04	0.12	15	-0.051	30	45
IL12/IL12R/TYK2/JAK2	0.062	0.21	0.49	27	-0.51	15	42
MAP2K3	0.086	0.23	0.49	19	-0.63	21	40
RIPK2	0.036	0.006	-10000	0	0	14	14
MAP2K6	0.089	0.22	0.53	12	-0.6	18	30
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	182	182
IL18RAP	0.038	0.02	0.088	2	-0.041	22	24
IL12Rbeta1/TYK2	0.049	0.062	0.18	7	-0.15	14	21
EOMES	-0.018	0.038	0.075	2	-0.099	48	50
STAT1 (dimer)	0.086	0.19	0.42	28	-0.43	11	39
T cell proliferation	0.074	0.18	0.4	34	-0.4	19	53
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.039	0.02	0.088	2	-0.041	22	24
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.043	0.17	-10000	0	-0.46	24	24
ATF2	0.084	0.21	0.47	19	-0.59	20	39

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.002	0.038	-10000	0	-10000	0	0
CRKL	0.035	0.009	-10000	0	0	29	29
Rac1/GDP	0.017	0.019	-10000	0	-0.13	5	5
DOCK1	0.024	0.017	-10000	0	0	175	175
ITGA4	0.036	0.006	-10000	0	0	13	13
alpha4/beta7 Integrin/MAdCAM1	0.083	0.035	-10000	0	-0.12	5	5
EPO	0.025	0.017	-10000	0	0	166	166
alpha4/beta7 Integrin	0.052	0.011	-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	0.039	0.025	-10000	0	-10000	0	0
EPO/EPOR (dimer)	0.035	0.026	-10000	0	-10000	0	0
lamellipodium assembly	-0.015	0.1	-10000	0	-0.35	23	23
PIK3CA	0.031	0.013	-10000	0	0	80	80
PI3K	0.019	0.075	-10000	0	-0.16	73	73
ARF6	0.035	0.008	-10000	0	0	27	27
JAK2	0.01	0.03	-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	0.034	0.009	-10000	0	0	32	32
cell adhesion	0.08	0.034	-10000	0	-0.12	5	5
CRKL/CBL	0.051	0.014	-10000	0	-10000	0	0
ITGB1	0.027	0.016	-10000	0	0	138	138
SRC	-0.034	0.058	0.19	4	-10000	0	4
ITGB7	0.036	0.005	-10000	0	0	11	11
RAC1	0.024	0.017	-10000	0	0	173	173
alpha4/beta1 Integrin/VCAM1	0.003	0.077	-10000	0	-0.12	126	126
p130Cas/Crk/Dock1	-0.031	0.063	0.2	4	-0.19	8	12
VCAM1	0.022	0.018	-10000	0	0	196	196
RHOA	0.035	0.007	-10000	0	0	18	18
alpha4/beta1 Integrin/Paxillin/GIT1	0.067	0.043	-10000	0	-10000	0	0
BCAR1	-0.033	0.051	0.18	4	-10000	0	4
EPOR	0.035	0.008	-10000	0	0	28	28
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.036	0.004	-10000	0	0	7	7
GIT1	0.036	0.003	-10000	0	0	4	4
Rac1/GTP	-0.016	0.1	-10000	0	-0.37	22	22

×

IL1-mediated 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
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	46	46
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.01	0.12	-10000	0	-0.27	67	67
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	0.092	94	-10000	0	94
IRAK/TRAF6/p62/Atypical PKCs	0.053	0.05	-10000	0	-0.13	28	28
IL1R2	0.03	0.014	-10000	0	0	90	90
IL1R1	0.036	0.006	-10000	0	0	13	13
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.015	0.1	-10000	0	-0.29	40	40
TOLLIP	0.034	0.009	-10000	0	0	30	30
TICAM2	0	0	-10000	0	-10000	0	0
MAP3K3	0.036	0.004	-10000	0	0	7	7
TAK1/TAB1/TAB2	0.056	0.047	-10000	0	-0.14	19	19
IKK complex/ELKS	-0.045	0.096	-10000	0	-0.25	17	17
JUN	-0.039	0.041	0.15	3	-0.21	9	12
MAP3K7	0.034	0.01	-10000	0	0	41	41
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.032	0.11	-10000	0	-0.14	107	107
IL1 alpha/IL1R1/IL1RAP/MYD88	0.065	0.069	-10000	0	-0.13	50	50
PIK3R1	0.032	0.012	-10000	0	0	63	63
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.074	0.075	-10000	0	-0.12	49	49
IL1 beta fragment/IL1R1/IL1RAP	0.026	0.081	0.16	8	-0.14	83	91
NFKB1	0.035	0.007	-10000	0	0	18	18
MAPK8	-0.033	0.036	0.16	3	-0.2	7	10
IRAK1	-0.018	0.01	-10000	0	-0.11	5	5
IL1RN/IL1R1	0.053	0.01	-10000	0	-10000	0	0
IRAK4	0.035	0.007	-10000	0	0	18	18
PRKCI	0.035	0.008	-10000	0	0	26	26
TRAF6	0.036	0.005	-10000	0	0	10	10
PI3K	0.019	0.075	-10000	0	-0.16	73	73
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.008	0.12	0.16	2	-0.26	71	73
CHUK	0.025	0.017	-10000	0	0	163	163
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.026	0.081	0.16	8	-0.14	83	91
IL1 beta/IL1R2	0.017	0.071	-10000	0	-0.14	71	71
IRAK/TRAF6/TAK1/TAB1/TAB2	0.059	0.067	-10000	0	-0.14	34	34
NF kappa B1 p50/RelA	0.016	0.098	-10000	0	-0.2	38	38
IRAK3	0.035	0.008	-10000	0	0	27	27
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.038	0.082	-10000	0	-0.13	81	81
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.008	0.076	-10000	0	-0.19	51	51
IL1 alpha/IL1R1/IL1RAP	0.049	0.053	-10000	0	-0.12	33	33
RELA	0.036	0.005	-10000	0	0	9	9
MAP3K7IP1	0.034	0.009	-10000	0	0	35	35
SQSTM1	0.034	0.009	-10000	0	0	35	35
MYD88	0.034	0.009	-10000	0	0	36	36
IRAK/TRAF6/MEKK3	0.049	0.038	-10000	0	-0.12	22	22
IL1RAP	0.03	0.014	-10000	0	0	94	94
UBE2N	0.036	0.006	-10000	0	0	13	13
IRAK/TRAF6	-0.039	0.062	0.062	69	-0.19	24	93
CASP1	0.029	0.015	-10000	0	0	108	108
IL1RN/IL1R2	0.045	0.021	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.038	0.096	-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	-0.3	38	38
PIK3CA	0.031	0.013	-10000	0	0	80	80
IL1RN	0.036	0.004	-10000	0	0	6	6
TRAF6/TAK1/TAB1/TAB2	0.065	0.059	-10000	0	-0.14	22	22
MAP2K6	-0.038	0.035	0.18	3	-0.2	7	10

×

IL6-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
BCL2L1	0.064	0.26	0.54	18	-0.66	26	44
CRP	0.06	0.26	0.61	9	-0.76	17	26
cell cycle arrest	0.052	0.29	0.51	21	-0.75	30	51
TIMP1	0.005	0.36	0.56	14	-0.8	68	82
IL6ST	0.028	0.033	0.09	1	-0.049	34	35
Rac1/GDP	0.039	0.11	0.3	16	-0.3	11	27
AP1	0.012	0.2	-10000	0	-0.56	37	37
GAB2	0.034	0.012	0.065	1	-0.001	48	49
TNFSF11	0.058	0.26	0.53	12	-0.73	20	32
HSP90B1	0.001	0.22	0.3	3	-0.84	30	33
GAB1	0.033	0.013	-10000	0	-0.001	60	60
MAPK14	0.029	0.065	-10000	0	-0.3	3	3
AKT1	-0.013	0.17	-10000	0	-0.52	35	35
FOXO1	-0.014	0.16	-10000	0	-0.5	36	36
MAP2K6	0.028	0.07	0.19	1	-0.28	6	7
mol:GTP	0	0.004	-10000	0	-0.022	1	1
MAP2K4	0.033	0.14	0.34	24	-0.36	16	40
MITF	0.032	0.083	0.22	11	-0.29	9	20
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.033	0.011	-10000	0	0	46	46
A2M	-0.076	0.34	-10000	0	-1.2	44	44
CEBPB	0.032	0.013	-10000	0	0	71	71
GRB2/SOS1/GAB family/SHP2	0.021	0.13	0.32	1	-0.48	23	24
STAT3	0.042	0.3	0.53	18	-0.8	30	48
STAT1	0.021	0.065	-10000	0	-0.72	3	3
CEBPD	0.024	0.33	0.54	11	-0.9	42	53
PIK3CA	0.031	0.014	-10000	0	-0.041	1	1
PI3K	0.019	0.075	-10000	0	-0.16	73	73
JUN	0.034	0.01	-10000	0	0	40	40
PIAS3/MITF	0.077	0.11	0.26	25	-0.29	10	35
MAPK11	0.026	0.064	-10000	0	-0.3	3	3
STAT3 (dimer)/FOXO1	-0.021	0.26	0.42	13	-0.62	53	66
GRB2/SOS1/GAB family	0.043	0.12	0.23	2	-0.31	30	32
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	0.004	0.1	0.18	10	-0.29	36	46
GRB2	0.036	0.008	-10000	0	-0.002	18	18
JAK2	0.031	0.014	-10000	0	0	83	83
LBP	0.064	0.25	0.51	20	-0.61	29	49
PIK3R1	0.032	0.013	-10000	0	-0.001	64	64
JAK1	0.03	0.026	-10000	0	-0.042	45	45
MYC	0.014	0.36	0.57	14	-0.87	57	71
FGG	0.058	0.26	0.57	8	-0.77	17	25
macrophage differentiation	0.052	0.29	0.51	21	-0.75	30	51
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.054	0.074	-10000	0	-0.19	5	5
JUNB	0.053	0.29	0.51	25	-0.82	28	53
FOS	0.025	0.017	-10000	0	0	158	158
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.028	0.083	0.22	13	-0.29	10	23
STAT1/PIAS1	0.071	0.12	0.3	12	-0.35	7	19
GRB2/SOS1/GAB family/SHP2/PI3K	-0.001	0.17	-10000	0	-0.5	36	36
STAT3 (dimer)	0.044	0.29	0.52	19	-0.79	30	49
PRKCD	0.11	0.22	0.41	95	-0.44	20	115
IL6R	0.03	0.027	-10000	0	-0.041	57	57
SOCS3	0.059	0.086	0.59	1	-10000	0	1
gp130 (dimer)/JAK1/JAK1/LMO4	0.045	0.087	0.18	1	-0.17	43	44
Rac1/GTP	0.033	0.11	0.31	10	-0.33	11	21
HCK	0.027	0.016	-10000	0	0	128	128
MAPKKK cascade	0.011	0.19	0.34	2	-0.59	35	37
bone resorption	0.06	0.25	0.52	13	-0.68	20	33
IRF1	0.053	0.29	0.54	18	-0.86	24	42
mol:GDP	0.031	0.09	0.23	18	-0.28	10	28
SOS1	0.001	0.004	0.025	10	-0.022	1	11
VAV1	0.03	0.09	0.23	21	-0.28	10	31
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.02	0.075	-10000	0	-0.32	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	0.074	-10000	0	-0.15	40	40
gp130 (dimer)/JAK2/JAK2/LMO4	0.048	0.063	-10000	0	-0.13	31	31
IL6	0.015	0.027	-10000	0	-0.045	11	11
PIAS3	0.036	0.006	-10000	0	0	14	14
PTPRE	0.01	0.03	-10000	0	-0.056	35	35
PIAS1	0.035	0.008	-10000	0	0	27	27
RAC1	0.024	0.018	-10000	0	0	174	174
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.018	0.052	0.17	5	-0.22	6	11
LMO4	0.029	0.033	0.09	1	-0.049	36	37
STAT3 (dimer)/PIAS3	0.015	0.26	0.46	6	-0.73	31	37
MCL1	-0.014	0.16	-10000	0	-0.7	17	17

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.035	0.008	-10000	0	0	27	27
mol:S1P	0.001	0.001	0.017	4	-10000	0	4
S1P1/S1P/Gi	-0.018	0.11	-10000	0	-0.26	63	63
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	-0.012	0.16	-10000	0	-0.5	44	44
AKT3	0.01	0.077	-10000	0	-0.37	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.035	0.008	-10000	0	0	27	27
GNAI2	0.034	0.011	-10000	0	-10000	0	0
GNAI3	0.036	0.007	-10000	0	0	15	15
GNAI1	0.018	0.019	-10000	0	0	263	263
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.001	0.002	0.018	4	-10000	0	4
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	0.033	0.01	-10000	0	0	45	45
mol:Ca2+	-0.001	0.1	0.19	1	-0.26	47	48
MAPK3	-0.008	0.098	0.17	1	-0.25	48	49
MAPK1	-0.003	0.094	0.17	1	-0.28	32	33
JAK2	-0.011	0.11	0.19	5	-0.31	43	48
CXCR4	-0.006	0.099	0.13	8	-0.26	47	55
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	0.019	-10000	0	-0.13	5	5
SRC	-0.007	0.098	0.17	1	-0.25	48	49
S1P/S1P3/Gi	0	0.1	0.19	1	-0.26	46	47
RAC1	0.024	0.017	-10000	0	0	173	173
RhoA/GTP	0.012	0.11	0.18	1	-0.27	40	41
VEGFA	0.002	0.002	0.032	3	-10000	0	3
S1P/S1P2/Gi	-0.004	0.099	0.16	1	-0.2	78	79
VEGFR1 homodimer/VEGFA homodimer	0.029	0.01	0.11	3	-10000	0	3
RHOA	0.035	0.007	-10000	0	0	18	18
S1P/S1P3/Gq	0.015	0.04	-10000	0	-0.15	26	26
GNAQ	0.034	0.009	-10000	0	0	31	31
GNAZ	0.031	0.014	-10000	0	-10000	0	0
G12/G13	0.025	0.047	-10000	0	-0.14	28	28
GNA14	0.034	0.009	-10000	0	0	30	30
GNA15	0.033	0.012	-10000	0	0	57	57
GNA12	0.023	0.018	-10000	0	0	193	193
GNA13	0.035	0.007	-10000	0	0	19	19
GNA11	0.033	0.011	-10000	0	0	54	54
Rac1/GTP	0.001	0.092	-10000	0	-0.29	27	27

×

Signaling events mediated by PTP1B

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
PDGFRB	0.035	0.008	-10000	0	0	27	27
Jak2/Leptin Receptor	-0.003	0.14	-10000	0	-0.33	53	53
PTP1B/AKT1	0	0.11	-10000	0	-0.27	41	41
FYN	0.03	0.014	-10000	0	0	90	90
p210 bcr-abl/PTP1B	-0.01	0.11	0.18	1	-0.28	42	43
EGFR	0.009	0.016	-10000	0	-0.031	3	3
EGF/EGFR	-0.033	0.09	-10000	0	-0.29	36	36
CSF1	0.036	0.005	-10000	0	0	8	8
AKT1	0.033	0.011	-10000	0	0	53	53
INSR	0.035	0.009	-10000	0	-0.001	26	26
PTP1B/N-cadherin	-0.005	0.12	-10000	0	-0.28	51	51
Insulin Receptor/Insulin	0.02	0.11	-10000	0	-0.28	27	27
HCK	0.027	0.016	-10000	0	0	128	128
CRK	0.035	0.008	-10000	0	0	23	23
TYK2	-0.009	0.12	0.3	19	-0.29	40	59
EGF	0.027	0.024	-10000	0	-0.031	66	66
YES1	0.034	0.01	-10000	0	0	41	41
CAV1	0.007	0.14	0.22	27	-0.31	45	72
TXN	0.035	0.011	-10000	0	0	40	40
PTP1B/IRS1/GRB2	0.006	0.12	-10000	0	-0.3	36	36
cell migration	0.01	0.11	0.28	42	-0.18	1	43
STAT3	0.034	0.01	-10000	0	0	37	37
PRLR	0.038	0.004	-10000	0	-10000	0	0
ITGA2B	0.036	0.004	-10000	0	0	5	5
CSF1R	0.027	0.016	-10000	0	0	131	131
Prolactin Receptor/Prolactin	0.057	0.012	-10000	0	-10000	0	0
FGR	0.033	0.011	-10000	0	0	54	54
PTP1B/p130 Cas	-0.012	0.1	0.16	1	-0.26	44	45
Crk/p130 Cas	-0.001	0.11	-10000	0	-0.26	48	48
DOK1	-0.008	0.1	0.18	7	-0.29	34	41
JAK2	-0.014	0.13	-10000	0	-0.34	54	54
Jak2/Leptin Receptor/Leptin	-0.014	0.12	-10000	0	-0.32	31	31
PIK3R1	0.032	0.012	-10000	0	0	63	63
PTPN1	-0.01	0.11	0.18	1	-0.28	42	43
LYN	0.031	0.013	-10000	0	0	74	74
CDH2	0.033	0.011	-10000	0	0	55	55
SRC	0.014	0.099	-10000	0	-0.46	17	17
ITGB3	0.036	0.003	-10000	0	0	4	4
CAT1/PTP1B	-0.01	0.17	0.24	17	-0.36	64	81
CAPN1	0.036	0.006	-10000	0	-0.004	8	8
CSK	0.035	0.007	-10000	0	0	21	21
PI3K	0.011	0.13	-10000	0	-0.29	41	41
mol:H2O2	0.004	0.005	0.029	6	-10000	0	6
STAT3 (dimer)	-0.012	0.11	-10000	0	-0.29	29	29
negative regulation of transcription	-0.014	0.13	-10000	0	-0.34	54	54
FCGR2A	0.028	0.015	-10000	0	0	114	114
FER	0.036	0.008	-10000	0	-0.002	15	15
alphaIIb/beta3 Integrin	0.053	0.006	-10000	0	-10000	0	0
BLK	0.035	0.007	-10000	0	0	17	17
Insulin Receptor/Insulin/Shc	0.059	0.036	-10000	0	-0.13	8	8
RHOA	0.035	0.007	-10000	0	0	18	18
LEPR	0.035	0.007	-10000	0	0	20	20
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.035	0.007	-10000	0	0	17	17
mol:NADPH	0.001	0.003	-10000	0	-10000	0	0
TRPV6	-0.006	0.15	0.2	6	-0.35	59	65
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	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.056	0.046	-10000	0	-0.12	23	23
CSF1/CSF1R	-0.002	0.13	-10000	0	-0.28	46	46
Ras protein signal transduction	-0.01	0.069	0.57	5	-0.21	1	6
IRS1	0.033	0.011	-10000	0	0	52	52
INS	0.036	0.007	-10000	0	-0.002	15	15
LEP	0.024	0.017	-10000	0	0	173	173
STAT5B	-0.004	0.11	0.17	2	-0.28	32	34
STAT5A	-0.004	0.11	-10000	0	-0.29	29	29
GRB2	0.035	0.007	-10000	0	0	17	17
PDGFB-D/PDGFRB	0.001	0.12	0.18	1	-0.27	44	45
CSN2	0.013	0.041	-10000	0	-10000	0	0
PIK3CA	0.031	0.013	-10000	0	0	80	80
LAT	-0.028	0.18	-10000	0	-0.46	65	65
YBX1	0.038	0.042	-10000	0	-0.29	8	8
LCK	0.035	0.007	-10000	0	0	17	17
SHC1	0.033	0.011	-10000	0	0	52	52
NOX4	0.034	0.015	-10000	0	0	82	82

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	0.052	0.056	-10000	0	-0.13	36	36
fibroblast growth factor receptor signaling pathway	0.051	0.055	-10000	0	-0.13	36	36
LAMA1	0	0	-10000	0	-10000	0	0
PRNP	0.033	0.011	-10000	0	0	52	52
GPC1/SLIT2	0.032	0.044	-10000	0	-0.14	23	23
SMAD2	-0.023	0.048	0.18	11	-0.2	3	14
GPC1/PrPc/Cu2+	0.026	0.058	-10000	0	-0.14	52	52
GPC1/Laminin alpha1	0.015	0.04	-10000	0	-0.13	35	35
TDGF1	0.035	0.007	-10000	0	0	18	18
CRIPTO/GPC1	0.038	0.047	-10000	0	-0.14	29	29
APP/GPC1	0.034	0.058	-10000	0	-0.16	38	38
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.023	0.033	0.089	22	-0.12	22	44
FLT1	0.034	0.009	-10000	0	0	33	33
GPC1/TGFB/TGFBR1/TGFBR2	0.051	0.053	-10000	0	-0.12	34	34
SERPINC1	0.036	0.005	-10000	0	0	11	11
FYN	-0.018	0.029	0.089	23	-0.12	8	31
FGR	-0.022	0.033	0.089	23	-0.12	21	44
positive regulation of MAPKKK cascade	-0.038	0.12	0.2	10	-0.3	61	71
SLIT2	0.029	0.015	-10000	0	0	103	103
GPC1/NRG	0.037	0.05	-10000	0	-0.14	35	35
NRG1	0.036	0.005	-10000	0	0	9	9
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.032	0.043	-10000	0	-0.12	35	35
LYN	-0.022	0.033	0.089	22	-0.12	23	45
mol:Spermine	-0.01	0.004	-10000	0	-10000	0	0
cell growth	0.051	0.055	-10000	0	-0.13	36	36
BMP signaling pathway	-0.032	0.012	0	64	-10000	0	64
SRC	-0.025	0.034	0.089	23	-0.12	28	51
TGFBR1	0.035	0.007	-10000	0	0	17	17
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	0.018	0.018	-10000	0	0	262	262
GPC1	0.032	0.012	-10000	0	0	64	64
TGFBR1 (dimer)	0.035	0.007	-10000	0	0	17	17
VEGFA	0	0	-10000	0	-10000	0	0
BLK	-0.025	0.034	0.089	24	-0.12	27	51
HCK	-0.018	0.03	0.089	19	-0.12	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	33	33
TGFBR2	0.035	0.009	-10000	0	0	29	29
cell death	0.034	0.057	-10000	0	-0.16	38	38
ATIII/GPC1	0.037	0.049	-10000	0	-0.14	33	33
PLA2G2A/GPC1	-0.005	0.074	-10000	0	-0.15	93	93
LCK	-0.024	0.034	0.089	24	-0.12	25	49
neuron differentiation	0.037	0.05	-10000	0	-0.14	35	35
PrPc/Cu2+	0.016	0.038	-10000	0	-0.13	31	31
APP	0.035	0.007	-10000	0	0	21	21
TGFBR2 (dimer)	0.034	0.009	-10000	0	0	29	29

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.012	0.05	-10000	0	-0.18	16	16
TRAF2/ASK1	0.032	0.043	-10000	0	-0.12	35	35
ATM	0.034	0.009	-10000	0	0	35	35
MAP2K3	0.014	0.099	0.24	1	-0.31	26	27
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.011	0.09	0.27	1	-0.3	19	20
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	67	67
TXN	0.007	0.002	-10000	0	0	40	40
CALM1	0.033	0.011	-10000	0	0	54	54
GADD45A	0.031	0.013	-10000	0	0	75	75
GADD45B	0.03	0.014	-10000	0	0	89	89
MAP3K1	0.035	0.007	-10000	0	0	20	20
MAP3K6	0.035	0.007	-10000	0	0	20	20
MAP3K7	0.034	0.01	-10000	0	0	41	41
MAP3K4	0.032	0.012	-10000	0	0	66	66
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.032	0.053	-10000	0	-0.14	38	38
TAK1/TAB family	0.009	0.054	-10000	0	-0.31	11	11
RAC1/OSM/MEKK3	0.03	0.026	-10000	0	-0.1	5	5
TRAF2	0.036	0.006	-10000	0	0	15	15
RAC1/OSM/MEKK3/MKK3	0.012	0.075	-10000	0	-0.26	22	22
TRAF6	0.009	0.033	-10000	0	-0.2	12	12
RAC1	0.024	0.017	-10000	0	0	173	173
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.017	0.018	-10000	0	0	272	272
CCM2	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.009	0.054	-10000	0	-0.13	53	53
MAPK11	0.033	0.011	-10000	0	0	49	49
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.011	0.066	-10000	0	-0.13	66	66
OSM/MEKK3	0.027	0.003	-10000	0	-10000	0	0
TAOK1	0.007	0.002	-10000	0	0	35	35
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	35	35
MAPK14	0.036	0.004	-10000	0	0	6	6
MAP3K7IP2	0.033	0.011	-10000	0	0	46	46
MAP3K5	0.03	0.014	-10000	0	0	90	90
MAP3K10	0.035	0.008	-10000	0	0	28	28
MAP3K3	0.036	0.004	-10000	0	0	7	7
TRX/ASK1	0.022	0.037	-10000	0	-0.16	16	16
GADD45/MTK1/MTK1	0.043	0.075	-10000	0	-0.13	64	64

×

ErbB2/ErbB3 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
USP8	-0.015	0.013	0.085	5	-10000	0	5
RAS family/GTP	0.013	0.11	0.22	1	-0.2	37	38
NFATC4	-0.021	0.067	0.19	13	-0.19	4	17
ERBB2IP	0.034	0.011	-10000	0	-0.001	42	42
HSP90 (dimer)	0	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.029	0.077	0.18	7	-0.21	7	14
JUN	-0.004	0.087	0.2	8	-0.36	7	15
HRAS	0.034	0.009	-10000	0	0	32	32
DOCK7	-0.036	0.068	0.15	11	-0.18	19	30
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.027	0.08	0.21	14	-0.13	84	98
AKT1	-0.01	0.008	0.015	20	-10000	0	20
BAD	-0.015	0.014	0.085	7	-10000	0	7
MAPK10	0.007	0.072	0.16	36	-0.16	10	46
mol:GTP	0	0.001	0.003	2	-0.005	24	26
ErbB2/ErbB3/neuregulin 1 beta	-0.03	0.083	0.2	7	-0.22	6	13
RAF1	-0.019	0.1	0.25	11	-0.24	32	43
ErbB2/ErbB3/neuregulin 2	0.002	0.073	0.2	17	-0.13	91	108
STAT3	-0.023	0.24	-10000	0	-0.9	35	35
cell migration	-0.005	0.071	0.19	20	-0.18	15	35
mol:PI-3-4-5-P3	-0.001	0.002	0.004	18	-0.004	19	37
cell proliferation	-0.041	0.24	0.42	4	-0.58	58	62
FOS	-0.032	0.2	0.37	6	-0.42	90	96
NRAS	0.032	0.012	-10000	0	0	63	63
mol:Ca2+	-0.029	0.077	0.18	7	-0.21	7	14
MAPK3	-0.019	0.18	0.4	3	-0.48	38	41
MAPK1	-0.044	0.22	0.4	3	-0.57	50	53
JAK2	-0.027	0.078	0.17	17	-0.22	5	22
NF2	0.01	0.008	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.005	0.08	0.15	13	-0.16	88	101
NRG1	0.036	0.005	-10000	0	0	9	9
GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
MAPK8	-0.014	0.087	0.2	3	-0.22	47	50
MAPK9	0.014	0.076	0.16	54	-0.15	3	57
ERBB2	-0.016	0.068	0.26	29	-10000	0	29
ERBB3	0.018	0.018	-10000	0	0	256	256
SHC1	0.033	0.011	-10000	0	0	52	52
RAC1	0.024	0.017	-10000	0	0	173	173
apoptosis	0.012	0.03	0.2	10	-0.07	4	14
STAT3 (dimer)	-0.021	0.24	-10000	0	-0.88	35	35
RNF41	-0.02	0.019	0.076	10	-0.12	2	12
FRAP1	-0.015	0.012	0.084	5	-10000	0	5
RAC1-CDC42/GTP	-0.022	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	0.35	5	-0.37	38	43
myelination	-0.033	0.072	0.24	7	-0.22	2	9
PPP3CB	-0.02	0.067	0.17	14	-0.21	4	18
KRAS	0.034	0.009	-10000	0	0	35	35
RAC1-CDC42/GDP	0.021	0.074	0.22	1	-0.16	45	46
NRG2	0.036	0.005	-10000	0	0	10	10
mol:GDP	-0.005	0.08	0.15	13	-0.16	88	101
SOS1	0	0.001	-10000	0	-0.004	8	8
MAP2K2	-0.028	0.1	0.22	11	-0.25	35	46
SRC	0.036	0.006	-10000	0	0	14	14
mol:cAMP	-0.001	0.001	0.003	7	-0.004	1	8
PTPN11	-0.031	0.083	0.18	19	-0.23	5	24
MAP2K1	-0.038	0.2	0.38	2	-0.55	38	40
heart morphogenesis	-0.029	0.077	0.18	7	-0.21	7	14
RAS family/GDP	0.021	0.11	0.24	1	-0.18	67	68
GRB2	0.035	0.007	-10000	0	0	17	17
PRKACA	0.018	0.009	-10000	0	-10000	0	0
CHRNE	0.001	0.025	0.068	4	-0.12	7	11
HSP90AA1	0	0	-10000	0	-10000	0	0
activation of caspase activity	0.01	0.008	-10000	0	-0.015	20	20
nervous system development	-0.029	0.077	0.18	7	-0.21	7	14
CDC42	0.035	0.008	-10000	0	0	24	24

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.001	0.009	0.026	1	-0.035	15	16
BUB1B	-0.023	0.084	0.12	22	-0.22	64	86
PLK1	0.004	0.023	0.083	17	-0.071	3	20
PLK1S1	0.002	0.014	0.049	21	-0.044	1	22
KIF2A	0.004	0.021	0.073	17	-0.064	3	20
regulation of mitotic centrosome separation	0.005	0.023	0.083	17	-0.071	3	20
GOLGA2	0.035	0.008	-10000	0	0	28	28
Hec1/SPC24	-0.004	0.01	-10000	0	-0.055	5	5
WEE1	-0.032	0.13	-10000	0	-0.46	36	36
cytokinesis	-0.021	0.11	0.15	12	-0.3	59	71
PP2A-alpha B56	0.051	0.087	-10000	0	-0.51	9	9
AURKA	0.002	0.016	0.056	21	-0.04	2	23
PICH/PLK1	-0.034	0.073	0.071	9	-0.18	87	96
CENPE	0.003	0.047	0.14	32	-0.1	6	38
RhoA/GTP	0.024	0.019	-10000	0	-0.13	7	7
positive regulation of microtubule depolymerization	0.004	0.02	0.073	17	-0.063	3	20
PPP2CA	0.035	0.007	-10000	0	0	21	21
FZR1	0.035	0.008	-10000	0	0	28	28
TPX2	-0.025	0.089	0.11	2	-0.22	83	85
PAK1	0.036	0.006	-10000	0	0	15	15
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	0.035	0.008	-10000	0	0	25	25
CLSPN	0.01	0.025	0.1	1	-0.2	5	6
GORASP1	0.034	0.009	-10000	0	0	33	33
metaphase	0.001	0.003	0.015	11	-0.011	1	12
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.002	0.014	0.049	21	-0.044	1	22
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	0.083	17	-0.071	3	20
ODF2	0.035	0.009	-10000	0	0	29	29
BUB1	0.02	0.074	-10000	0	-0.57	7	7
TPT1	-0.002	0.05	-10000	0	-0.18	34	34
CDC25C	0.011	0.03	-10000	0	-0.22	7	7
CDC25B	0.012	0.032	-10000	0	-0.029	175	175
SGOL1	0.001	0.009	0.035	15	-0.026	1	16
RHOA	0.035	0.007	-10000	0	0	18	18
CCNB1/CDK1	-0.02	0.12	-10000	0	-0.24	92	92
CDC14B	-0.011	0.004	0.01	6	-10000	0	6
CDC20	0.028	0.016	-10000	0	0	125	125
PLK1/PBIP1	-0.015	0.036	0.069	6	-0.089	77	83
mitosis	-0.001	0.003	0.012	9	-10000	0	9
FBXO5	-0.017	0.061	0.12	17	-0.16	51	68
CDC2	0.015	0.023	-10000	0	-0.03	42	42
NDC80	0	0	-10000	0	-10000	0	0
metaphase plate congression	0.002	0.059	-10000	0	-0.26	23	23
ERCC6L	-0.045	0.1	-10000	0	-0.22	92	92
NLP/gamma Tubulin	0.001	0.027	0.073	12	-0.1	21	33
microtubule cytoskeleton organization	-0.002	0.05	-10000	0	-0.18	34	34
G2/M transition DNA damage checkpoint	-0.001	0.002	0.01	5	-10000	0	5
PPP1R12A	0.035	0.008	-10000	0	0	24	24
interphase	-0.001	0.002	0.01	5	-10000	0	5
PLK1/PRC1-2	0.007	0.075	0.13	1	-0.14	86	87
GRASP65/GM130/RAB1/GTP/PLK1	0.046	0.053	-10000	0	-0.12	29	29
RAB1A	0.035	0.007	-10000	0	0	18	18
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.002	0.018	0.066	18	-0.051	1	19
mitotic prometaphase	-0.001	0.005	0.02	23	-10000	0	23
proteasomal ubiquitin-dependent protein catabolic process	-0.048	0.1	0.18	2	-0.21	119	121
microtubule-based process	0.019	0.024	0.1	4	-0.066	2	6
Golgi organization	0.005	0.023	0.083	17	-0.071	3	20
Cohesin/SA2	0.02	0.033	0.1	4	-0.094	21	25
PPP1CB/MYPT1	0.046	0.036	-10000	0	-0.15	14	14
KIF20A	0.029	0.015	-10000	0	0	109	109
APC/C/CDC20	0.019	0.024	0.11	5	-10000	0	5
PPP2R1A	0.032	0.012	-10000	0	0	61	61
chromosome segregation	-0.015	0.035	0.068	6	-0.088	77	83
PRC1	0.028	0.016	-10000	0	0	123	123
ECT2	0.001	0.059	0.14	51	-0.1	30	81
C13orf34	0.003	0.019	0.069	18	-0.056	2	20
NUDC	0.001	0.059	-10000	0	-0.26	23	23
regulation of attachment of spindle microtubules to kinetochore	-0.023	0.083	0.12	22	-0.21	64	86
spindle assembly	0.002	0.025	0.085	15	-0.078	13	28
spindle stabilization	0.002	0.014	0.048	21	-0.044	1	22
APC/C/HCDH1	0.024	0.026	0.089	1	-0.12	15	16
MKLP2/PLK1	0.019	0.024	0.1	4	-0.066	2	6
CCNB1	0.014	0.028	-10000	0	-0.028	116	116
PPP1CB	0.036	0.006	-10000	0	0	15	15
BTRC	0.025	0.017	-10000	0	0	155	155
ROCK2	0.016	0.029	-10000	0	-0.21	3	3
TUBG1	0.002	0.05	0.1	1	-0.22	22	23
G2/M transition of mitotic cell cycle	-0.047	0.1	0.14	18	-0.23	92	110
MLF1IP	-0.009	0.006	0.01	1	-10000	0	1
INCENP	0.036	0.005	-10000	0	0	8	8

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	34	34
mol:PIP3	-0.018	0.057	0.1	5	-0.23	22	27
FRAP1	0.03	0.1	0.28	2	-0.46	14	16
AKT1	0.007	0.1	0.17	94	-0.26	29	123
INSR	0.035	0.008	-10000	0	0	25	25
Insulin Receptor/Insulin	0.046	0.013	-10000	0	-10000	0	0
mol:GTP	0.032	0.11	0.2	58	-0.26	29	87
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.005	0.047	-10000	0	-0.19	15	15
TSC2	0.035	0.008	-10000	0	0	28	28
RHEB/GDP	0.002	0.076	-10000	0	-0.24	28	28
TSC1	0.034	0.01	-10000	0	0	40	40
Insulin Receptor/IRS1	0.022	0.061	-10000	0	-0.25	23	23
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.023	0.071	0.16	1	-0.24	11	12
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.036	0.085	0.26	10	-0.32	4	14
MAP3K5	-0.026	0.084	0.16	1	-0.22	73	74
PIK3R1	0.033	0.012	-10000	0	0	63	63
apoptosis	-0.026	0.084	0.16	1	-0.22	73	74
mol:LY294002	0	0	0.001	9	-0.001	18	27
EIF4B	0.029	0.082	0.24	11	-0.31	5	16
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.03	0.072	0.23	8	-0.28	4	12
eIF4E/eIF4G1/eIF4A1	0.009	0.075	-10000	0	-0.3	16	16
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.022	0.082	-10000	0	-0.23	32	32
mTOR/RHEB/GTP/Raptor/GBL	0.006	0.06	0.19	9	-0.2	13	22
FKBP1A	0.034	0.01	-10000	0	0	44	44
RHEB/GTP	0.014	0.086	0.23	5	-0.24	27	32
mol:Amino Acids	0	0	0.001	9	-0.001	18	27
FKBP12/Rapamycin	0.022	0.023	-10000	0	-0.13	10	10
PDPK1	-0.021	0.061	0.16	15	-0.23	19	34
EIF4E	0.034	0.01	-10000	0	0	38	38
ASK1/PP5C	-0.034	0.24	-10000	0	-0.56	79	79
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.02	0.11	-10000	0	-0.34	30	30
TSC1/TSC2	0.035	0.12	0.21	58	-0.28	29	87
tumor necrosis factor receptor activity	0	0	0.001	18	-0.001	9	27
RPS6	0.031	0.013	-10000	0	0	81	81
PPP5C	0.034	0.01	-10000	0	0	39	39
EIF4G1	0.033	0.011	-10000	0	0	49	49
IRS1	0.001	0.058	-10000	0	-0.26	23	23
INS	0.036	0.006	-10000	0	0	14	14
PTEN	0.026	0.017	-10000	0	0	148	148
PDK2	-0.021	0.061	0.16	15	-0.23	19	34
EIF4EBP1	-0.02	0.25	-10000	0	-1.1	24	24
PIK3CA	0.031	0.014	-10000	0	0	80	80
PPP2R5D	0.025	0.097	0.27	3	-0.41	14	17
peptide biosynthetic process	-0.02	0.017	0.18	3	-10000	0	3
RHEB	0.024	0.017	-10000	0	0	173	173
EIF4A1	0.035	0.007	-10000	0	0	17	17
mol:Rapamycin	0	0.001	0.003	29	-0.003	16	45
EEF2	-0.021	0.017	0.18	3	-10000	0	3
eIF4E/4E-BP1	-0.004	0.24	-10000	0	-1.1	24	24

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.01	0.057	-10000	0	-0.2	28	28
epithelial cell differentiation	0.063	0.051	-10000	0	-0.14	25	25
CYFIP2	0.031	0.013	-10000	0	0	78	78
ENAH	-0.041	0.07	0.25	11	-0.26	8	19
EGFR	0.009	0.016	-10000	0	0	381	381
EPHA2	0.033	0.011	-10000	0	0	54	54
MYO6	-0.029	0.049	0.18	9	-0.21	13	22
CTNNB1	0.036	0.006	-10000	0	0	15	15
ABI1/Sra1/Nap1	0.031	0.063	-10000	0	-0.12	58	58
AQP5	-0.02	0.051	0.21	2	-0.28	9	11
CTNND1	0.034	0.009	-10000	0	0	32	32
mol:PI-4-5-P2	-0.031	0.044	0.18	6	-0.2	13	19
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	0.036	0.002	-10000	0	0	2	2
AQP3	-0.035	0.075	-10000	0	-0.3	32	32
cortical microtubule organization	0.063	0.051	-10000	0	-0.14	25	25
GO:0000145	-0.03	0.04	0.16	6	-0.19	13	19
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.07	0.054	-10000	0	-0.14	25	25
MLLT4	0.034	0.009	-10000	0	0	36	36
ARF6/GDP	-0.052	0.039	-10000	0	-0.16	34	34
ARF6	0.035	0.008	-10000	0	0	27	27
Ephrin A1/EPHA2/NCK1/GIT1	0.076	0.052	-10000	0	-0.12	24	24
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.029	0.079	0.16	1	-0.28	36	37
PVRL2	0.034	0.009	-10000	0	0	35	35
ZYX	-0.021	0.046	0.18	6	-0.21	15	21
ARF6/GTP	0.079	0.059	-10000	0	-0.12	23	23
CDH1	0.034	0.01	-10000	0	0	38	38
EGFR/EGFR/EGF/EGF	-0.001	0.059	-10000	0	-0.13	66	66
RhoA/GDP	0.063	0.056	-10000	0	-0.14	29	29
actin cytoskeleton organization	-0.024	0.045	0.17	6	-0.22	12	18
IGF-1R heterotetramer	0.032	0.012	-10000	0	0	57	57
GIT1	0.036	0.003	-10000	0	0	4	4
IGF1R	0.033	0.012	-10000	0	0	57	57
IGF1	0.035	0.008	-10000	0	0	23	23
DIAPH1	-0.12	0.27	-10000	0	-0.57	59	59
Wnt receptor signaling pathway	-0.063	0.051	0.14	25	-10000	0	25
RHOA	0.035	0.007	-10000	0	0	18	18
RhoA/GTP	-0.053	0.041	-10000	0	-0.16	38	38
CTNNA1	0.035	0.007	-10000	0	0	20	20
VCL	-0.024	0.046	0.17	6	-0.23	12	18
EFNA1	0.033	0.011	-10000	0	0	50	50
LPP	-0.03	0.045	0.18	4	-0.22	13	17
Ephrin A1/EPHA2	0.046	0.062	-10000	0	-0.14	40	40
SEC6/SEC8	-0.044	0.028	-10000	0	-0.14	25	25
MGAT3	-0.028	0.044	0.19	8	-0.19	8	16
HGF/MET	0.036	0.05	-10000	0	-0.14	16	16
HGF	0.024	0.017	-10000	0	0	177	177
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.01	0.057	-10000	0	-0.21	28	28
actin cable formation	-0.039	0.1	0.32	9	-0.3	32	41
KIAA1543	-0.025	0.036	0.16	7	-0.18	8	15
KIFC3	-0.031	0.042	0.19	5	-0.19	8	13
NCK1	0.035	0.008	-10000	0	0	27	27
EXOC3	0.036	0.003	-10000	0	0	4	4
ACTN1	-0.026	0.049	0.19	7	-0.21	16	23
NCK1/GIT1	0.05	0.022	-10000	0	-0.14	5	5
mol:GDP	0.063	0.051	-10000	0	-0.14	25	25
EXOC4	0	0	-10000	0	-10000	0	0
STX4	-0.028	0.03	0.053	22	-0.13	25	47
PIP5K1C	-0.031	0.045	0.18	6	-0.21	13	19
LIMA1	0	0	-10000	0	-10000	0	0
ABI1	0.026	0.017	-10000	0	0	152	152
ROCK1	-0.034	0.085	0.34	11	-0.29	5	16
adherens junction assembly	-0.023	0.073	0.23	6	-0.33	14	20
IGF-1R heterotetramer/IGF1	0.048	0.062	-10000	0	-0.14	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	191	191
PLEKHA7	-0.028	0.03	0.053	22	-0.13	25	47
mol:GTP	0.073	0.051	-10000	0	-0.12	24	24
establishment of epithelial cell apical/basal polarity	-0.038	0.039	0.12	13	-0.18	10	23
cortical actin cytoskeleton stabilization	0.01	0.057	-10000	0	-0.2	28	28
regulation of cell-cell adhesion	-0.024	0.045	0.17	6	-0.22	12	18
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.01	0.057	-10000	0	-0.21	28	28

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.035	0.007	-10000	0	0	21	21
HDAC2	0.032	0.012	-10000	0	0	67	67
GNB1/GNG2	0.028	0.034	-10000	0	-0.11	14	14
forebrain development	0.034	0.063	0.25	4	-0.42	3	7
GNAO1	0.03	0.014	-10000	0	0	87	87
SMO/beta Arrestin2	0.033	0.031	-10000	0	-0.14	4	4
SMO	0.024	0.018	-10000	0	0	176	176
ARRB2	0.035	0.008	-10000	0	0	26	26
GLI3/SPOP	0.002	0.11	0.27	1	-0.31	35	36
mol:GTP	0	0.001	-10000	0	-10000	0	0
GSK3B	0.034	0.01	-10000	0	0	40	40
GNAI2	0.034	0.01	-10000	0	0	43	43
SIN3/HDAC complex	0.055	0.041	-10000	0	-0.12	17	17
GNAI1	0.018	0.018	-10000	0	0	263	263
XPO1	0.037	0.005	-10000	0	0	5	5
GLI1/Su(fu)	0.012	0.047	-10000	0	-0.3	5	5
SAP30	0.035	0.007	-10000	0	0	20	20
mol:GDP	0.024	0.018	-10000	0	0	176	176
MIM/GLI2A	0.041	0.013	0.12	11	-10000	0	11
IFT88	0.035	0.008	-10000	0	0	28	28
GNAI3	0.036	0.006	-10000	0	0	15	15
GLI2	0.001	0.089	-10000	0	-0.34	21	21
GLI3	-0.013	0.1	0.27	1	-0.31	32	33
CSNK1D	0.035	0.007	-10000	0	0	20	20
CSNK1E	0.032	0.012	-10000	0	0	67	67
SAP18	0.034	0.01	-10000	0	0	41	41
embryonic digit morphogenesis	0.035	0.008	-10000	0	0	28	28
GNG2	0	0	-10000	0	-10000	0	0
Gi family/GTP	-0.01	0.088	-10000	0	-0.2	69	69
SIN3B	0.034	0.009	-10000	0	0	29	29
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	17	17
FOXA2	0.05	0.041	-10000	0	-0.45	2	2
neural tube patterning	0.034	0.063	0.25	4	-0.42	3	7
SPOP	0.035	0.008	-10000	0	0	23	23
Su(fu)/PIAS1	0.047	0.038	0.098	151	-0.083	9	160
GNB1	0.035	0.007	-10000	0	0	20	20
CSNK1G2	0.034	0.009	-10000	0	0	30	30
CSNK1G3	0.036	0.006	-10000	0	0	13	13
MTSS1	0.041	0.013	0.12	11	-10000	0	11
embryonic limb morphogenesis	0.034	0.063	0.25	4	-0.42	3	7
SUFU	0.002	0.01	-10000	0	-0.11	4	4
LGALS3	0.028	0.015	-10000	0	0	114	114
catabolic process	0.012	0.14	0.31	2	-0.42	33	35
GLI3A/CBP	0.044	0.008	-10000	0	-10000	0	0
KIF3A	0.033	0.011	-10000	0	0	55	55
GLI1	0.034	0.064	0.25	4	-0.43	3	7
RAB23	0.034	0.009	-10000	0	0	31	31
CSNK1A1	0.036	0.006	-10000	0	0	14	14
IFT172	0	0	-10000	0	-10000	0	0
RBBP7	0.036	0.005	-10000	0	0	8	8
Su(fu)/Galectin3	0.038	0.04	0.098	123	-0.11	8	131
GNAZ	0.031	0.013	-10000	0	0	81	81
RBBP4	0.033	0.011	-10000	0	0	56	56
CSNK1G1	0.036	0.006	-10000	0	0	14	14
PIAS1	0.035	0.008	-10000	0	0	27	27
PRKACA	0.035	0.008	-10000	0	0	25	25
GLI2/SPOP	0.016	0.097	-10000	0	-0.32	25	25
STK36	0.001	0.003	0.022	4	-10000	0	4
Gi family/GNB1/GNG2/GDP	-0.015	0.1	-10000	0	-0.36	30	30
PTCH1	0.033	0.059	0.23	4	-0.38	3	7
MIM/GLI1	0.057	0.069	0.35	2	-0.39	3	5
CREBBP	0.044	0.008	-10000	0	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.002	0.091	0.16	2	-0.24	44	46

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.027	0.073	0.19	21	-0.27	9	30
FYN	-0.011	0.1	0.23	10	-0.3	33	43
LAT/GRAP2/SLP76	0.02	0.072	0.22	4	-0.29	10	14
IKBKB	0.036	0.003	-10000	0	0	4	4
AKT1	0.005	0.083	0.2	18	-0.24	21	39
B2M	0.036	0.01	-10000	0	0	27	27
IKBKG	-0.003	0.034	0.086	22	-0.095	11	33
MAP3K8	0.022	0.018	-10000	0	0	196	196
mol:Ca2+	-0.01	0.01	0.088	1	-0.038	2	3
integrin-mediated signaling pathway	0.024	0.007	-10000	0	-0.11	1	1
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.007	0.1	0.24	18	-0.28	25	43
TRPV6	0.4	0.59	1.2	168	-10000	0	168
CD28	0.037	0.001	-10000	0	-10000	0	0
SHC1	0.018	0.077	0.2	30	-0.32	9	39
receptor internalization	0.018	0.06	0.17	8	-0.29	8	16
PRF1	-0.14	0.31	-10000	0	-0.6	149	149
KRAS	0.034	0.009	-10000	0	0	35	35
GRB2	0.035	0.007	-10000	0	0	17	17
COT/AKT1	0.006	0.063	0.19	6	-0.21	18	24
LAT	0.012	0.072	0.21	13	-0.31	10	23
EntrezGene:6955	0.001	0.004	0.014	41	-10000	0	41
CD3D	0.035	0.011	-10000	0	0	44	44
CD3E	0.038	0.007	-10000	0	0	9	9
CD3G	0.037	0.008	-10000	0	0	17	17
RASGRP2	0.006	0.02	-10000	0	-0.14	6	6
RASGRP1	-0.024	0.13	0.22	27	-0.24	93	120
HLA-A	0.037	0.007	-10000	0	0	13	13
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	0.009	0.053	0.13	37	-0.1	18	55
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.005	0.037	-10000	0	-0.12	25	25
PRKCA	-0.001	0.057	0.17	22	-0.18	6	28
GRAP2	0.034	0.009	-10000	0	0	35	35
mol:IP3	0.002	0.053	-10000	0	-0.24	8	8
EntrezGene:6957	0.001	0.004	0.014	41	-10000	0	41
TCR/CD3/MHC I/CD8	0.018	0.048	0.15	11	-0.17	11	22
ORAI1	-0.35	0.5	0.38	5	-1.1	168	173
CSK	0.013	0.072	0.21	14	-0.3	11	25
B7 family/CD28	0.062	0.096	0.26	27	-0.29	9	36
CHUK	0.025	0.017	-10000	0	0	163	163
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.015	0.074	0.2	9	-0.32	11	20
PTPN6	0.008	0.076	0.22	12	-0.31	12	24
VAV1	0.018	0.076	0.21	26	-0.31	9	35
Monovalent TCR/CD3	0.022	0.017	0.1	9	-10000	0	9
CBL	0.036	0.004	-10000	0	0	7	7
LCK	0.006	0.09	0.23	14	-0.28	19	33
PAG1	0.015	0.071	0.2	13	-0.3	11	24
RAP1A	0.036	0.005	-10000	0	0	11	11
TCR/CD3/MHC I/CD8/LCK	0.014	0.075	0.2	10	-0.31	12	22
CD80	0.036	0.007	-10000	0	0	16	16
CD86	0.032	0.012	-10000	0	0	64	64
PDK1/CARD11/BCL10/MALT1	0.002	0.046	-10000	0	-0.14	24	24
HRAS	0.034	0.009	-10000	0	0	32	32
GO:0035030	0.011	0.073	0.19	24	-0.24	11	35
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	0.006	0.09	0.23	24	-0.28	15	39
CSK/PAG1	0.011	0.071	0.21	13	-0.29	11	24
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	0.049	0.035	-10000	0	-0.14	13	13
GRAP2/SLP76	0.029	0.083	0.23	6	-0.3	12	18
STIM1	-0.06	0.18	1.2	7	-10000	0	7
RAS family/GTP	0.004	0.072	0.16	22	-0.16	37	59
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.019	0.062	0.18	8	-0.3	8	16
mol:DAG	-0.02	0.036	-10000	0	-0.22	8	8
RAP1A/GDP	0.009	0.027	0.069	29	-0.051	15	44
PLCG1	0.035	0.007	-10000	0	0	19	19
CD247	0.001	0.004	0.014	41	-10000	0	41
cytotoxic T cell degranulation	-0.14	0.3	-10000	0	-0.58	149	149
RAP1A/GTP	0.003	0.008	-10000	0	-0.053	6	6
mol:PI-3-4-5-P3	0.009	0.09	0.23	19	-0.24	25	44
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.011	0.067	0.2	2	-0.29	8	10
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	0.066	0.2	6	-0.3	7	13
MALT1	0.034	0.009	-10000	0	0	32	32
TRAF6	0.036	0.005	-10000	0	0	10	10
CD8 heterodimer	0.003	0.008	0.027	44	-10000	0	44
CARD11	0	0	-10000	0	-10000	0	0
PRKCB	-0.016	0.026	-10000	0	-0.16	8	8
PRKCE	-0.001	0.057	0.17	21	-0.18	6	27
PRKCQ	0.008	0.094	0.24	22	-0.3	15	37
LCP2	0.031	0.013	-10000	0	0	77	77
BCL10	0.035	0.007	-10000	0	0	20	20
regulation of survival gene product expression	0.005	0.076	0.19	21	-0.22	19	40
IKK complex	-0.002	0.038	0.12	18	-0.088	4	22
RAS family/GDP	-0.004	0.015	-10000	0	-0.04	37	37
MAP3K14	0.009	0.063	0.17	26	-0.17	18	44
PDPK1	0.005	0.079	0.21	20	-0.23	19	39
TCR/CD3/MHC I/CD8/Fyn	0.01	0.068	0.18	1	-0.28	12	13

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.035	0.009	-10000	0	0	29	29
RAS family/GTP/Tiam1	-0.006	0.085	-10000	0	-0.2	65	65
NT3 (dimer)/TRKC	0.046	0.026	-10000	0	-0.14	6	6
NT3 (dimer)/TRKB	0.026	0.069	-10000	0	-0.12	73	73
SHC/Grb2/SOS1/GAB1/PI3K	-0.008	0.095	-10000	0	-0.21	75	75
RAPGEF1	0.035	0.007	-10000	0	0	19	19
BDNF	0.032	0.012	-10000	0	0	67	67
PIK3CA	0.031	0.013	-10000	0	0	80	80
DYNLT1	0.033	0.01	-10000	0	0	44	44
NTRK1	0.035	0.006	-10000	0	0	16	16
NTRK2	0.026	0.016	-10000	0	0	142	142
NTRK3	0.034	0.01	-10000	0	0	38	38
NT-4/5 (dimer)/TRKB	0.013	0.058	-10000	0	-0.12	77	77
neuron apoptosis	-0.007	0.12	0.32	42	-0.23	1	43
SHC 2-3/Grb2	0.007	0.13	0.24	1	-0.34	42	43
SHC1	0.033	0.011	-10000	0	0	52	52
SHC2	-0.012	0.12	-10000	0	-0.43	29	29
SHC3	-0.012	0.12	-10000	0	-0.41	31	31
STAT3 (dimer)	0.022	0.087	-10000	0	-0.28	36	36
NT3 (dimer)/TRKA	0.059	0.03	-10000	0	-10000	0	0
RIN/GDP	0.001	0.074	0.18	5	-0.22	25	30
GIPC1	0.035	0.008	-10000	0	0	24	24
KRAS	0.034	0.009	-10000	0	0	35	35
DNAJA3	-0.005	0.04	0.14	3	-0.16	3	6
RIN/GTP	0.011	0.035	-10000	0	-0.13	26	26
CCND1	-0.011	0.11	-10000	0	-0.49	25	25
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	46	46
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.04	0.031	-10000	0	-0.12	14	14
GRB2	0.035	0.007	-10000	0	0	17	17
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	257	257
RhoG/GTP/ELMO1/DOCK1	0.008	0.046	-10000	0	-0.12	46	46
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.034	0.009	-10000	0	0	32	32
DOCK1	0.024	0.017	-10000	0	0	175	175
GAB2	0.033	0.011	-10000	0	0	47	47
RIT2	0.024	0.017	-10000	0	0	170	170
RIT1	0.032	0.012	-10000	0	0	60	60
FRS2	0.034	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	0.009	0.048	0.16	2	-0.17	12	14
mol:GDP	-0.001	0.1	0.22	5	-0.32	24	29
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.002	0.043	-10000	0	-0.13	45	45
RIT1/GDP	0.008	0.081	0.19	6	-0.23	23	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	0.069	-10000	0	-0.12	70	70
KIDINS220/CRKL/C3G	0.05	0.015	-10000	0	-10000	0	0
SHC/RasGAP	0.037	0.051	-10000	0	-0.15	31	31
FRS2 family/SHP2	0.067	0.028	-10000	0	-0.12	6	6
SHC/GRB2/SOS1/GAB1	0.048	0.046	-10000	0	-0.11	25	25
RIT1/GTP	0.015	0.04	-10000	0	-0.13	35	35
NT3 (dimer)	0.035	0.008	-10000	0	0	23	23
RAP1/GDP	-0.002	0.06	-10000	0	-0.18	27	27
KIDINS220/CRKL	0.034	0.009	-10000	0	0	29	29
BDNF (dimer)	0.032	0.012	-10000	0	0	67	67
ubiquitin-dependent protein catabolic process	0.043	0.017	-10000	0	-0.11	1	1
Schwann cell development	-0.01	0.016	-10000	0	-0.056	34	34
EHD4	0.034	0.01	-10000	0	0	41	41
FRS2 family/GRB2/SOS1	0.062	0.029	-10000	0	-0.11	8	8
FRS2 family/SHP2/CRK family/C3G/GAB2	0.008	0.07	-10000	0	-0.25	20	20
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.036	0.005	-10000	0	0	11	11
CDC42/GTP	0.019	0.081	-10000	0	-0.15	68	68
ABL1	0.032	0.013	-10000	0	0	70	70
SH2B family/GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
Rap1/GTP	0.003	0.068	-10000	0	-0.22	18	18
STAT3	0.022	0.087	-10000	0	-0.28	36	36
axon guidance	0.005	0.07	-10000	0	-0.14	73	73
MAPK3	-0.007	0.055	0.18	37	-10000	0	37
MAPK1	-0.008	0.05	0.18	30	-10000	0	30
CDC42/GDP	0.011	0.08	0.18	10	-0.22	23	33
NTF3	0.035	0.008	-10000	0	0	23	23
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.043	0.025	-10000	0	-0.12	9	9
PI3K	0.019	0.075	-10000	0	-0.16	73	73
FRS3	0.036	0.002	-10000	0	0	2	2
FAIM	0.034	0.009	-10000	0	0	30	30
GAB1	0.032	0.012	-10000	0	0	59	59
RASGRF1	-0.006	0.039	0.14	2	-0.13	4	6
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.018	0.02	0.089	10	-0.12	2	12
RGS19	0.033	0.011	-10000	0	0	51	51
CDC42	0.035	0.008	-10000	0	0	24	24
RAS family/GTP	0.009	0.1	0.23	1	-0.38	22	23
Rac1/GDP	0.009	0.068	0.18	7	-0.23	18	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	0.043	0.017	-10000	0	-0.12	1	1
MAP2K1	-0.011	0.058	0.18	17	-0.19	6	23
NGFR	0.031	0.013	-10000	0	0	71	71
NGF (dimer)/TRKA/GIPC/GAIP	0.014	0.043	-10000	0	-0.22	9	9
RAS family/GTP/PI3K	-0.023	0.1	-10000	0	-0.21	99	99
FRS2 family/SHP2/GRB2/SOS1	0.076	0.039	-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	26	26
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.024	0.017	-10000	0	0	173	173
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	0.011	0.086	-10000	0	-0.48	12	12
RASA1	0.034	0.009	-10000	0	0	32	32
TRKA/c-Abl	0.032	0.058	-10000	0	-0.14	48	48
SQSTM1	0.034	0.009	-10000	0	0	35	35
BDNF (dimer)/TRKB/GIPC	0.049	0.074	-10000	0	-0.12	66	66
NGF (dimer)/TRKA/p62/Atypical PKCs	0.053	0.033	-10000	0	-0.1	14	14
MATK	0.034	0.009	-10000	0	0	30	30
NEDD4L	0.033	0.01	-10000	0	0	44	44
RAS family/GDP	-0.02	0.056	-10000	0	-0.16	48	48
NGF (dimer)/TRKA	0.009	0.04	0.15	4	-0.13	4	8
Rac1/GTP	-0.014	0.055	-10000	0	-0.2	24	24
FRS2 family/SHP2/CRK family	0.087	0.056	-10000	0	-0.12	17	17

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	-0.018	0.021	0.092	16	-10000	0	16
BAD/BCL-XL/YWHAZ	0.048	0.034	-10000	0	-0.12	12	12
CDKN1B	-0.024	0.12	-10000	0	-0.33	57	57
CDKN1A	-0.024	0.12	-10000	0	-0.33	57	57
FRAP1	0.035	0.007	-10000	0	0	17	17
PRKDC	0.033	0.01	-10000	0	0	44	44
FOXO3	-0.019	0.11	-10000	0	-0.31	58	58
AKT1	-0.019	0.12	-10000	0	-0.33	58	58
BAD	0.036	0.006	-10000	0	0	14	14
AKT3	0.014	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	-0.019	0.11	-10000	0	-0.31	58	58
AKT1/ASK1	-0.009	0.12	-10000	0	-0.32	57	57
BAD/YWHAZ	0.063	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	0.32	57	-10000	0	57
TSC1	-0.025	0.12	-10000	0	-0.34	56	56
YWHAZ	0.035	0.007	-10000	0	0	21	21
AKT1/RAF1	-0.002	0.13	-10000	0	-0.34	60	60
EP300	0.033	0.011	-10000	0	0	49	49
mol:GDP	-0.019	0.12	-10000	0	-0.32	58	58
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	-0.027	0.12	-10000	0	-0.33	59	59
YWHAQ	0.036	0.005	-10000	0	0	9	9
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	31	31
negative regulation of cell cycle	0.005	0.11	0.41	19	-10000	0	19
YWHAH	0.031	0.013	-10000	0	0	73	73
AKT1S1	-0.019	0.11	-10000	0	-0.31	58	58
CASP9	-0.021	0.11	0.2	3	-0.32	57	60
YWHAB	0.035	0.008	-10000	0	0	24	24
p27Kip1/KPNA1	-0.008	0.13	0.27	3	-0.32	58	61
GBL	0.036	0.006	-10000	0	0	15	15
PDK1/Src/Hsp90	0.047	0.01	-10000	0	-10000	0	0
YWHAE	0.035	0.008	-10000	0	0	27	27
SRC	0.036	0.006	-10000	0	0	14	14
AKT2/p21CIP1	-0.025	0.11	0.23	1	-0.31	44	45
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.015	0.067	-10000	0	-0.44	7	7
CHUK	-0.021	0.1	-10000	0	-0.33	46	46
BAD/BCL-XL	0.004	0.12	-10000	0	-0.32	56	56
mTORC2	0.06	0.031	-10000	0	-0.12	8	8
AKT2	0.014	0.004	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	-0.007	0.13	-10000	0	-0.44	25	25
PDPK1	0.036	0.004	-10000	0	0	7	7
MDM2	-0.017	0.12	-10000	0	-0.32	56	56
MAPKKK cascade	0.002	0.13	0.33	60	-10000	0	60
MDM2/Cbp/p300	0.015	0.13	0.27	1	-0.31	55	56
TSC1/TSC2	-0.03	0.13	0.26	8	-0.34	59	67
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.12	0.26	1	-0.3	55	56
glucose import	-0.008	0.022	0.2	3	-10000	0	3
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.012	0.082	-10000	0	-0.33	9	9
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.008	0.022	0.2	3	-10000	0	3
GSK3A	-0.019	0.11	0.26	5	-0.32	53	58
FOXO1	-0.019	0.11	-10000	0	-0.31	58	58
GSK3B	-0.024	0.12	-10000	0	-0.34	57	57
SFN	0.031	0.013	-10000	0	0	78	78
G1/S transition of mitotic cell cycle	-0.028	0.12	0.25	8	-0.33	58	66
p27Kip1/14-3-3 family	0.008	0.11	-10000	0	-0.53	13	13
PRKACA	0.035	0.008	-10000	0	0	25	25
KPNA1	0.035	0.008	-10000	0	0	27	27
HSP90AA1	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0.024	0.017	-10000	0	0	173	173
CREBBP	0.036	0.005	-10000	0	0	8	8

×

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	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.035	0.007	-10000	0	0	19	19
RAC1-CDC42/GTP/PAK family	0.002	0.048	-10000	0	-0.14	41	41
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.034	0.01	-10000	0	0	41	41
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	0.004	-10000	0	0	7	7
FYN	0.03	0.014	-10000	0	0	90	90
MAP3K12	0.036	0.005	-10000	0	0	9	9
FGR	0.033	0.011	-10000	0	0	54	54
p38 alpha/TAB1	0.018	0.11	0.18	4	-0.26	41	45
PRKG1	0.026	0.016	-10000	0	0	141	141
DUSP8	0.034	0.01	-10000	0	0	39	39
PGK/cGMP/p38 alpha	0.004	0.098	0.17	1	-0.25	40	41
apoptosis	0.017	0.1	0.18	4	-0.24	41	45
RAL/GTP	0.026	0.038	-10000	0	-0.12	20	20
LYN	0.031	0.013	-10000	0	0	74	74
DUSP1	0.031	0.013	-10000	0	0	77	77
PAK1	0.036	0.006	-10000	0	0	15	15
SRC	0.036	0.006	-10000	0	0	14	14
RAC1/OSM/MEKK3/MKK3	0.044	0.037	-10000	0	-0.11	5	5
TRAF6	0.036	0.005	-10000	0	0	10	10
RAC1	0.024	0.017	-10000	0	0	173	173
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	0.03	0.028	-10000	0	-0.12	5	5
MAPK11	-0.002	0.13	0.19	6	-0.32	44	50
BLK	0.035	0.007	-10000	0	0	17	17
HCK	0.027	0.016	-10000	0	0	128	128
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	48	48
TRAF6/MEKK3	0.045	0.01	-10000	0	-0.1	1	1
MAP3K7IP1	0.034	0.009	-10000	0	0	35	35
MAPK14	0.009	0.11	0.17	6	-0.26	43	49
positive regulation of innate immune response	0.001	0.14	0.21	6	-0.34	47	53
LCK	0.035	0.007	-10000	0	0	17	17
p38alpha-beta/MKP7	-0.001	0.14	0.19	8	-0.33	47	55
p38alpha-beta/MKP5	0.014	0.14	0.23	5	-0.34	40	45
PGK/cGMP	0.02	0.012	-10000	0	-10000	0	0
PAK2	0.035	0.007	-10000	0	0	20	20
p38alpha-beta/MKP1	0.005	0.14	0.23	5	-0.33	48	53
CDC42	0.035	0.008	-10000	0	0	24	24
RALB	0.035	0.007	-10000	0	0	17	17
RALA	0.024	0.018	-10000	0	0	180	180
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	0.035	0.007	-10000	0	0	17	17
PTK2	0.034	0.009	-10000	0	0	32	32
CRKL	-0.017	0.044	0.097	27	-0.15	24	51
GRB2/SOS1/SHC	0.04	0.031	-10000	0	-0.12	14	14
HRAS	0.034	0.009	-10000	0	0	32	32
IRS1/Crk	0.018	0.047	-10000	0	-0.14	35	35
IGF-1R heterotetramer/IGF1/PTP1B	0.052	0.055	-10000	0	-0.14	29	29
AKT1	-0.034	0.075	0.15	28	-0.22	30	58
BAD	-0.038	0.072	0.15	24	-0.22	29	53
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.018	0.045	0.1	28	-0.16	24	52
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.025	0.048	0.16	1	-0.14	29	30
RAF1	-0.032	0.14	-10000	0	-0.55	28	28
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.046	0.054	0.17	1	-0.14	30	31
YWHAZ	0.035	0.007	-10000	0	0	21	21
IGF-1R heterotetramer/IGF1/IRS1	0.033	0.049	0.17	1	-0.16	24	25
PIK3CA	0.031	0.013	-10000	0	0	80	80
RPS6KB1	-0.033	0.071	0.16	31	-0.2	22	53
GNB2L1	0.036	0.002	-10000	0	0	2	2
positive regulation of MAPKKK cascade	-0.033	0.12	0.23	3	-0.43	28	31
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	0.015	0.054	-10000	0	-0.14	43	43
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.066	0.057	-10000	0	-0.12	34	34
IGF-1R heterotetramer	0.036	0.014	0.092	1	-0.034	1	2
IGF-1R heterotetramer/IGF1/IRS/Nck	0.048	0.06	0.18	1	-0.14	36	37
Crk/p130 Cas/Paxillin	0.038	0.056	0.2	3	-0.13	35	38
IGF1R	0.036	0.014	0.092	1	-0.034	1	2
IGF1	0.033	0.026	0.092	1	-0.055	33	34
IRS2/Crk	-0.03	0.057	0.1	19	-0.18	32	51
PI3K	0.039	0.087	0.2	1	-0.14	78	79
apoptosis	0.037	0.076	0.21	30	-0.16	21	51
HRAS/GDP	0.021	0.027	-10000	0	-0.13	15	15
PRKCD	0.004	0.064	0.17	8	-0.21	24	32
RAF1/14-3-3 E	-0.012	0.13	0.23	1	-0.48	28	29
BAD/14-3-3	-0.039	0.08	0.17	21	-0.22	30	51
PRKCZ	-0.027	0.07	0.15	32	-0.2	22	54
Crk/p130 Cas/Paxillin/FAK1	-0.046	0.072	0.13	26	-0.22	29	55
PTPN1	0.034	0.009	-10000	0	0	30	30
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.006	0.06	-10000	0	-0.21	26	26
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.038	0.07	-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	0.027	0.051	0.13	5	-0.14	35	40
GRB10	0.021	0.018	-10000	0	0	220	220
PTPN11	-0.018	0.045	0.1	28	-0.15	24	52
IRS1	0.01	0.042	0.12	5	-0.16	24	29
IRS2	-0.019	0.049	0.1	20	-0.19	24	44
IGF-1R heterotetramer/IGF1	0.039	0.051	0.15	1	-0.17	24	25
GRB2	0.035	0.007	-10000	0	0	17	17
PDPK1	-0.026	0.076	0.17	30	-0.2	22	52
YWHAE	0.035	0.008	-10000	0	0	27	27
PRKD1	-0.002	0.064	0.2	1	-0.24	25	26
SHC1	0.033	0.011	-10000	0	0	52	52

×

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

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
MET/RANBP9	0.03	0.035	-10000	0	-0.14	9	9
CRKL	0.042	0.11	0.28	6	-0.4	21	27
mol:PIP3	-0.009	0.1	-10000	0	-0.79	7	7
AKT1	-0.02	0.092	0.25	1	-0.7	7	8
PTK2B	0.035	0.006	-10000	0	0	16	16
RAPGEF1	0.04	0.11	0.31	7	-0.38	21	28
RANBP10	0.036	0.005	-10000	0	0	10	10
PIK3CA	0.031	0.013	-10000	0	0	80	80
HGF/MET/SHIP2	0.042	0.038	-10000	0	-0.12	2	2
MAP3K5	0.04	0.11	0.29	5	-0.38	20	25
HGF/MET/CIN85/CBL/ENDOPHILINS	0.04	0.035	-10000	0	-10000	0	0
AP1	0.035	0.079	0.15	97	-0.15	44	141
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	-0.79	109	109
STAT3 (dimer)	0.011	0.059	-10000	0	-0.28	11	11
GAB1/CRKL/SHP2/PI3K	0.058	0.13	0.31	2	-0.4	21	23
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.059	0.12	0.29	3	-0.39	21	24
PTPN11	0.036	0.005	-10000	0	0	11	11
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.035	0.007	-10000	0	0	19	19
PTEN	0.026	0.017	-10000	0	0	148	148
ELK1	0.12	0.18	0.36	169	-10000	0	169
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.012	0.034	0.16	1	-0.17	6	7
PAK1	-0.024	0.088	-10000	0	-0.68	7	7
HGF/MET/RANBP10	0.042	0.037	-10000	0	-10000	0	0
HRAS	0.011	0.083	-10000	0	-0.47	11	11
DOCK1	0.031	0.11	0.28	5	-0.39	20	25
GAB1	0.045	0.12	-10000	0	-0.41	21	21
CRK	0.043	0.11	0.29	3	-0.4	21	24
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.069	-10000	0	-0.42	10	10
JUN	0.034	0.01	-10000	0	0	40	40
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.01	0.017	-10000	0	-0.12	1	1
PIK3R1	0.032	0.012	-10000	0	0	63	63
cell morphogenesis	0.024	0.11	0.28	21	-0.32	14	35
GRB2/SHC	0.077	0.065	0.17	115	-0.12	2	117
FOS	0.025	0.017	-10000	0	0	158	158
GLMN	0.004	0.004	0.068	2	-10000	0	2
cell motility	0.12	0.18	0.36	169	-10000	0	169
HGF/MET/MUC20	0.029	0.024	-10000	0	-10000	0	0
cell migration	0.075	0.063	0.17	115	-0.12	2	117
GRB2	0.035	0.007	-10000	0	0	17	17
CBL	0.036	0.004	-10000	0	0	7	7
MET/RANBP10	0.033	0.026	-10000	0	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.013	0.048	-10000	0	-0.19	20	20
MET/MUC20	0.017	0.013	-10000	0	-10000	0	0
RAP1B	0.039	0.11	0.3	7	-0.36	21	28
RAP1A	0.034	0.11	0.3	8	-0.36	20	28
HGF/MET/RANBP9	0.04	0.042	-10000	0	-0.12	8	8
RAF1	0.038	0.1	0.31	1	-0.45	13	14
STAT3	0.009	0.058	-10000	0	-0.29	11	11
cell proliferation	0.039	0.081	0.24	14	-0.28	9	23
RPS6KB1	0.014	0.018	-10000	0	-10000	0	0
MAPK3	0.084	0.17	0.4	29	-10000	0	29
MAPK1	0.12	0.22	0.59	50	-10000	0	50
RANBP9	0.035	0.007	-10000	0	0	18	18
MAPK8	-0.048	0.16	0.27	1	-0.41	30	31
SRC	0.007	0.046	-10000	0	-0.26	6	6
PI3K	0.061	0.074	0.17	95	-0.16	9	104
MET/Glomulin	0.016	0.026	-10000	0	-0.087	17	17
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	0.029	0.1	0.29	1	-0.43	14	15
MET	0.023	0.018	-10000	0	0	191	191
MAP4K1	0.048	0.11	0.3	4	-0.38	20	24
PTK2	0.034	0.009	-10000	0	0	32	32
MAP2K2	0.038	0.11	0.3	14	-0.42	12	26
BAD	-0.027	0.088	-10000	0	-0.63	8	8
MAP2K4	0.033	0.11	0.27	9	-0.35	20	29
SHP2/GRB2/SOS1/GAB1	0.016	0.085	-10000	0	-0.35	19	19
INPPL1	0.036	0.006	-10000	0	0	12	12
PXN	0.036	0.004	-10000	0	0	7	7
SH3KBP1	0	0	-10000	0	-10000	0	0
HGS	0.001	0.018	0.076	15	-0.12	1	16
PLCgamma1/PKC	0.025	0.013	-10000	0	-0.13	3	3
HGF	0.024	0.017	-10000	0	0	177	177
RASA1	0.034	0.009	-10000	0	0	32	32
NCK1	0.035	0.008	-10000	0	0	27	27
PTPRJ	0.036	0.005	-10000	0	0	11	11
NCK/PLCgamma1	0.083	0.059	0.17	120	-0.12	1	121
PDPK1	-0.012	0.096	0.29	1	-0.74	7	8
HGF/MET/SHIP	0.029	0.024	-10000	0	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.008	-9999	0	25	25
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.035	0.008	-9999	0	25	25
CHUK	0.025	0.017	-9999	0	163	163
NF kappa B2 p100/RelB	0.066	0.059	-9999	-0.12	10	10
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	158	158
NF kappa B2 p52/RelB	0.033	0.023	-9999	-10000	0	0
regulation of B cell activation	0.032	0.023	-9999	-10000	0	0

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.05	0.073	-10000	0	-0.12	37	37
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.035	0.009	-10000	0	0	29	29
STAT1 (dimer)/Cbp/p300	0.022	0.083	0.27	5	-0.22	17	22
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.042	0.062	-10000	0	-0.14	39	39
antigen processing and presentation of peptide antigen via MHC class I	-0.025	0.079	0.12	5	-0.18	65	70
CaM/Ca2+	0.046	0.078	-10000	0	-0.14	37	37
RAP1A	0.036	0.005	-10000	0	0	11	11
STAT1 (dimer)/SHP2	-0.022	0.059	0.16	17	-0.18	9	26
AKT1	-0.033	0.084	0.27	5	-0.23	30	35
MAP2K1	-0.028	0.056	0.21	5	-0.22	6	11
MAP3K11	-0.022	0.059	0.26	4	-0.19	5	9
IFNGR1	0.031	0.019	-10000	0	-0.036	19	19
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.028	0.12	-10000	0	-0.3	62	62
Rap1/GTP	-0.039	0.036	0.049	1	-0.16	7	8
CRKL/C3G	0.05	0.015	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.064	0.076	-10000	0	-0.13	35	35
CEBPB	-0.009	0.12	0.35	3	-0.44	19	22
STAT3	0.034	0.01	-10000	0	0	37	37
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.061	0.089	-10000	0	-0.74	3	3
STAT1	-0.024	0.06	0.25	5	-0.18	9	14
CALM1	0.033	0.011	-10000	0	0	54	54
IFN-gamma (dimer)	0.03	0.021	-10000	0	-0.037	38	38
PIK3CA	0.031	0.013	-10000	0	0	80	80
STAT1 (dimer)/PIAS1	-0.025	0.07	0.24	6	-0.21	15	21
CEBPB/PTGES2/Cbp/p300	0.008	0.09	-10000	0	-0.3	21	21
mol:Ca2+	0.046	0.07	-10000	0	-0.12	37	37
MAPK3	0.006	0.079	0.34	1	-0.68	2	3
STAT1 (dimer)	-0.027	0.11	0.19	7	-0.26	55	62
MAPK1	-0.041	0.2	-10000	0	-0.75	35	35
JAK2	0.027	0.022	-10000	0	-0.037	34	34
PIK3R1	0.032	0.012	-10000	0	0	63	63
JAK1	0.033	0.017	-10000	0	-0.036	17	17
CAMK2D	0	0	-10000	0	-10000	0	0
DAPK1	-0.001	0.096	0.32	3	-0.44	9	12
SMAD7	-0.009	0.06	0.16	22	-0.15	16	38
CBL/CRKL/C3G	0.018	0.071	0.27	4	-0.19	4	8
PI3K	0.026	0.094	-10000	0	-0.21	28	28
IFNG	0.03	0.021	-10000	0	-0.037	38	38
apoptosis	0.012	0.086	0.34	2	-0.41	8	10
CAMK2G	0.024	0.018	-10000	0	0	179	179
STAT3 (dimer)	0.034	0.01	-10000	0	0	37	37
CAMK2A	0.036	0.005	-10000	0	0	10	10
CAMK2B	0.017	0.018	-10000	0	0	272	272
FRAP1	-0.039	0.077	0.25	4	-0.22	31	35
PRKCD	-0.032	0.08	0.32	4	-0.22	19	23
RAP1B	0	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.025	0.079	0.12	5	-0.18	65	70
PTPN2	0.035	0.007	-10000	0	0	18	18
EP300	0.034	0.011	-10000	0	0	49	49
IRF1	-0.035	0.058	0.21	3	-0.28	12	15
STAT1 (dimer)/PIASy	-0.025	0.065	0.26	5	-0.19	6	11
SOCS1	0.019	0.083	-10000	0	-1	3	3
mol:GDP	-0.021	0.066	0.17	21	-0.18	4	25
CASP1	-0.019	0.073	0.18	15	-0.16	62	77
PTGES2	0.035	0.007	-10000	0	0	20	20
IRF9	-0.002	0.044	0.12	15	-0.13	15	30
mol:PI-3-4-5-P3	0.013	0.082	-10000	0	-0.19	31	31
RAP1/GDP	-0.031	0.052	0.11	17	-0.18	5	22
CBL	-0.022	0.058	0.25	4	-0.19	4	8
MAP3K1	-0.023	0.056	0.25	3	-0.19	4	7
PIAS1	0.035	0.008	-10000	0	0	27	27
PIAS4	0.035	0.008	-10000	0	0	27	27
antigen processing and presentation of peptide antigen via MHC class II	-0.025	0.079	0.12	5	-0.18	65	70
PTPN11	-0.016	0.059	0.16	25	-0.18	6	31
CREBBP	0.037	0.005	-10000	0	0	8	8
RAPGEF1	0.035	0.007	-10000	0	0	19	19

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.028	0.11	0.32	9	-0.32	18	27
PDGFB-D/PDGFRB/SLAP	0.018	0.072	-10000	0	-0.15	71	71
PDGFB-D/PDGFRB/APS/CBL	0.045	0.022	-10000	0	-0.12	7	7
AKT1	-0.026	0.089	0.26	13	-0.24	15	28
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.019	0.1	0.29	9	-0.32	22	31
PIK3CA	0.031	0.013	-10000	0	0	80	80
FGR	0.006	0.1	0.27	3	-0.5	13	16
mol:Ca2+	0.011	0.1	0.26	8	-0.37	20	28
MYC	0.01	0.26	0.4	21	-0.67	51	72
SHC1	0.033	0.011	-10000	0	0	52	52
HRAS/GDP	0.012	0.066	0.17	26	-0.18	13	39
LRP1/PDGFRB/PDGFB	0.048	0.055	-10000	0	-0.13	32	32
GRB10	0.021	0.018	-10000	0	0	220	220
PTPN11	0.036	0.005	-10000	0	0	11	11
GO:0007205	0.011	0.1	0.26	8	-0.37	20	28
PTEN	0.026	0.017	-10000	0	0	148	148
GRB2	0.035	0.007	-10000	0	0	17	17
GRB7	0.036	0.006	-10000	0	0	14	14
PDGFB-D/PDGFRB/SHP2	0.047	0.033	-10000	0	-0.14	13	13
PDGFB-D/PDGFRB/GRB10	0.021	0.049	-10000	0	-0.14	30	30
cell cycle arrest	0.017	0.072	-10000	0	-0.15	71	71
HRAS	0.034	0.009	-10000	0	0	32	32
HIF1A	-0.03	0.081	0.23	14	-0.25	13	27
GAB1	0.006	0.12	0.28	9	-0.37	30	39
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.005	0.12	0.3	14	-0.33	29	43
PDGFB-D/PDGFRB	0.056	0.053	0.19	1	-0.14	14	15
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.044	0.04	-10000	0	-0.14	20	20
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.025	0.12	0.29	8	-0.3	32	40
positive regulation of MAPKKK cascade	0.047	0.033	-10000	0	-0.14	13	13
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	0.011	0.1	0.26	8	-0.38	20	28
E5	-0.001	0.002	-10000	0	-10000	0	0
CSK	0.034	0.011	-10000	0	-0.009	29	29
PDGFB-D/PDGFRB/GRB7	0.05	0.022	-10000	0	-0.14	4	4
SHB	0.033	0.011	-10000	0	0	51	51
BLK	0.012	0.077	0.3	2	-0.43	7	9
PTPN2	0.032	0.018	-10000	0	-0.019	49	49
PDGFB-D/PDGFRB/SNX15	0.049	0.025	-10000	0	-0.14	7	7
BCAR1	0	0	-10000	0	-10000	0	0
VAV2	-0.006	0.15	0.29	13	-0.41	42	55
CBL	0.036	0.004	-10000	0	0	7	7
PDGFB-D/PDGFRB/DEP1	0.049	0.026	-10000	0	-0.14	7	7
LCK	0.017	0.06	0.26	4	-0.35	2	6
PDGFRB	0.031	0.021	0.064	2	-0.019	71	73
ACP1	0.035	0.007	-10000	0	0	18	18
HCK	-0.043	0.18	0.22	1	-0.5	61	62
ABL1	0.002	0.11	0.26	9	-0.34	29	38
PDGFB-D/PDGFRB/CBL	0.006	0.13	0.28	6	-0.43	27	33
PTPN1	0.032	0.018	-10000	0	-0.015	60	60
SNX15	0.036	0.004	-10000	0	0	6	6
STAT3	0.034	0.01	-10000	0	0	37	37
STAT1	0.034	0.01	-10000	0	0	40	40
cell proliferation	0.018	0.24	0.38	25	-0.6	51	76
SLA	0.027	0.016	-10000	0	0	134	134
actin cytoskeleton reorganization	-0.018	0.067	0.2	30	-0.19	7	37
SRC	0.017	0.052	0.35	1	-10000	0	1
PI3K	-0.047	0.044	-10000	0	-0.18	31	31
PDGFB-D/PDGFRB/GRB7/SHC	0.061	0.037	-10000	0	-0.12	10	10
SH2B2	0	0	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.019	0.1	0.29	9	-0.33	22	31
LYN	-0.035	0.16	-10000	0	-0.47	53	53
LRP1	0.031	0.013	-10000	0	0	71	71
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	0.066	0.065	-10000	0	-0.14	25	25
SPHK1	0.033	0.011	0.058	1	0	50	51
EDG1	0.034	0.011	0.058	1	0	45	46
mol:DAG	0.011	0.1	0.26	8	-0.38	20	28
PLCG1	0.011	0.1	0.26	8	-0.38	20	28
NHERF/PDGFRB	0.062	0.036	-10000	0	-0.12	11	11
YES1	-0.009	0.13	0.23	1	-0.52	25	26
cell migration	0.061	0.036	-10000	0	-0.12	11	11
SHC/Grb2/SOS1	0.068	0.061	-10000	0	-0.13	20	20
SLC9A3R2	0.036	0.005	-10000	0	0	9	9
SLC9A3R1	0.034	0.01	-10000	0	0	37	37
NHERF1-2/PDGFRB/PTEN	0.06	0.052	-10000	0	-0.11	13	13
FYN	-0.055	0.19	0.22	1	-0.45	81	82
DOK1	-0.017	0.053	0.17	27	-10000	0	27
HRAS/GTP	0.021	0.027	-10000	0	-0.13	15	15
PDGFB	0.034	0.01	-10000	0	0	37	37
RAC1	0.031	0.19	0.32	35	-0.43	47	82
PRKCD	-0.015	0.053	0.18	26	-10000	0	26
FER	-0.016	0.054	0.18	25	-10000	0	25
MAPKKK cascade	-0.014	0.061	0.15	44	-0.18	5	49
RASA1	-0.015	0.055	0.18	26	-0.21	3	29
NCK1	0.035	0.008	-10000	0	0	27	27
NCK2	0.035	0.007	-10000	0	0	17	17
p62DOK/Csk	-0.014	0.063	0.18	31	-0.2	3	34
PDGFB-D/PDGFRB/SHB	0.045	0.027	-10000	0	-0.14	5	5
chemotaxis	0.002	0.11	0.26	9	-0.33	29	38
STAT1-3-5/STAT1-3-5	0.062	0.072	-10000	0	-0.14	30	30
Bovine Papilomavirus E5/PDGFRB	0.02	0.024	-10000	0	-0.14	7	7
PTPRJ	0.036	0.005	-10000	0	0	11	11

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.027	0.016	-9999	0	138	138
ITGB7	0.036	0.005	-9999	0	11	11
ITGA4	0.036	0.006	-9999	0	13	13
alpha4/beta7 Integrin	0.052	0.011	-9999	-9999	0	0
alpha4/beta1 Integrin	0.039	0.025	-9999	-9999	0	0

×

S1P1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.017	0.051	-10000	0	-0.18	28	28
PDGFRB	0.036	0.009	-10000	0	-0.001	28	28
SPHK1	0.017	0.04	-10000	0	-0.76	1	1
mol:S1P	0.019	0.042	-10000	0	-0.68	1	1
S1P1/S1P/Gi	-0.001	0.14	0.25	12	-0.47	27	39
GNAO1	0.032	0.015	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/PLCgamma1	0.027	0.14	0.25	18	-0.39	28	46
PLCG1	-0.005	0.13	0.24	15	-0.42	28	43
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.036	0.009	-10000	0	-0.001	28	28
GNAI2	0.036	0.012	-10000	0	0	43	43
GNAI3	0.037	0.007	-10000	0	0	15	15
GNAI1	0.018	0.019	-10000	0	0	263	263
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	0.007	0.073	0.12	5	-0.27	27	32
S1P1/S1P	0.024	0.077	0.21	4	-0.28	17	21
negative regulation of cAMP metabolic process	0	0.14	0.25	13	-0.46	27	40
MAPK3	0.002	0.14	0.29	16	-0.46	24	40
calcium-dependent phospholipase C activity	0	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.017	0.019	-10000	0	-0.13	5	5
RhoA/GDP	0.024	0.019	-10000	0	-0.13	7	7
KDR	0.027	0.034	0.093	1	-0.13	18	19
PLCB2	0.036	0.089	0.21	26	-0.26	17	43
RAC1	0.024	0.017	-10000	0	0	173	173
RhoA/GTP	0.018	0.066	-10000	0	-0.25	17	17
receptor internalization	0.023	0.073	0.2	4	-0.26	17	21
PTGS2	0.032	0.15	0.36	6	-0.48	15	21
Rac1/GTP	0.009	0.057	-10000	0	-0.28	11	11
RHOA	0.035	0.007	-10000	0	0	18	18
VEGFA	-0.001	0.021	-10000	0	-0.098	23	23
negative regulation of T cell proliferation	0	0.14	0.25	13	-0.46	27	40
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.032	0.015	-10000	0	-10000	0	0
MAPK1	0.003	0.14	0.29	13	-0.49	21	34
S1P1/S1P/PDGFB-D/PDGFRB	0.052	0.1	0.24	17	-0.29	20	37
ABCC1	0.036	0.008	-10000	0	0	19	19

×

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	0.053	0.036	-10000	0	-0.097	20	20
ER alpha/Gai/GDP/Gbeta gamma	-0.038	0.17	-10000	0	-0.52	41	41
AKT1	-0.053	0.23	-10000	0	-0.68	49	49
PIK3CA	0.031	0.013	-10000	0	0	80	80
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.046	0.24	-10000	0	-0.7	48	48
mol:Ca2+	0.001	0.044	0.17	4	-0.25	3	7
IGF1R	0.033	0.012	-10000	0	0	57	57
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	0.052	0.22	0.63	51	-10000	0	51
RhoA/GTP	-0.041	0.038	-10000	0	-0.13	48	48
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.012	0.15	-10000	0	-0.39	46	46
regulation of stress fiber formation	0.038	0.058	0.18	20	-0.18	8	28
E2/ERA-ERB (dimer)	0.045	0.015	-10000	0	-10000	0	0
KRAS	0.034	0.009	-10000	0	0	35	35
G13/GTP	0.043	0.013	-10000	0	-10000	0	0
pseudopodium formation	-0.038	0.058	0.18	8	-0.18	20	28
E2/ER alpha (dimer)/PELP1	0.044	0.023	-10000	0	-0.11	7	7
GRB2	0.035	0.007	-10000	0	0	17	17
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	32	32
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)	0.025	0.006	-10000	0	-10000	0	0
mol:GDP	0.004	0.057	-10000	0	-0.19	27	27
mol:NADP	-0.012	0.16	-10000	0	-0.44	44	44
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	0.002	0.042	0.17	4	-0.33	1	5
IGF-1R heterotetramer	0.032	0.012	-10000	0	0	57	57
PLCB1	0.01	0.04	-10000	0	-0.33	1	1
PLCB2	0.008	0.04	-10000	0	-0.33	1	1
IGF1	0.035	0.008	-10000	0	0	23	23
mol:L-citrulline	-0.012	0.16	-10000	0	-0.44	44	44
RHOA	0.035	0.007	-10000	0	0	18	18
Gai/GDP	-0.066	0.24	-10000	0	-0.64	69	69
JNK cascade	0.025	0.006	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	0.034	0.009	-10000	0	0	31	31
GNAQ	0.034	0.009	-10000	0	0	31	31
ESR1	0.035	0.009	-10000	0	0	29	29
Gq family/GDP/Gbeta gamma	-0.003	0.15	-10000	0	-0.47	37	37
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.015	0.14	-10000	0	-0.68	17	17
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	0.001	0.16	0.25	2	-0.39	46	48
GNAZ	0.031	0.013	-10000	0	0	81	81
E2/ER alpha (dimer)	0.026	0.006	-10000	0	-10000	0	0
STRN	0.036	0.003	-10000	0	0	3	3
GNAL	0.036	0.006	-10000	0	0	13	13
PELP1	0.035	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	43	43
GNAI3	0.036	0.006	-10000	0	0	15	15
GNAI1	0.018	0.018	-10000	0	0	263	263
HBEGF	-0.02	0.18	0.31	10	-0.48	42	52
cAMP biosynthetic process	0.037	0.015	-10000	0	-10000	0	0
SRC	-0.041	0.16	0.2	5	-0.48	44	49
PI3K	0.019	0.075	-10000	0	-0.16	73	73
GNB1	0.035	0.007	-10000	0	0	20	20
G13/GDP/Gbeta gamma	0.022	0.068	-10000	0	-0.17	34	34
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.025	0.12	-10000	0	-0.33	44	44
Gs family/GTP	0.047	0.019	-10000	0	-10000	0	0
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.042	0.063	-10000	0	-0.13	53	53
vasodilation	-0.01	0.16	-10000	0	-0.42	44	44
mol:DAG	0.002	0.042	0.17	4	-0.33	1	5
Gs family/GDP/Gbeta gamma	0.004	0.062	-10000	0	-0.18	30	30
MSN	-0.039	0.057	0.17	7	-0.19	21	28
Gq family/GTP	0.022	0.043	-10000	0	-0.34	1	1
mol:PI-3-4-5-P3	-0.045	0.23	-10000	0	-0.67	48	48
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	-10000	0	44
GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
RhoA/GDP	0.018	0.067	-10000	0	-0.19	27	27
NOS3	-0.014	0.17	-10000	0	-0.47	44	44
GNA11	0.033	0.011	-10000	0	0	54	54
MAPKKK cascade	0	0.15	-10000	0	-0.47	36	36
E2/ER alpha (dimer)/PELP1/Src	-0.003	0.16	0.27	2	-0.41	45	47
ruffle organization	-0.038	0.058	0.18	8	-0.18	20	28
ROCK2	-0.034	0.061	0.2	7	-0.19	12	19
GNA14	0.034	0.009	-10000	0	0	30	30
GNA15	0.033	0.012	-10000	0	0	57	57
GNA13	0.035	0.007	-10000	0	0	19	19
MMP9	-0.025	0.17	0.37	4	-0.46	45	49
MMP2	-0.025	0.17	0.24	7	-0.46	46	53

×

Caspase cascade in apoptosis

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
TOP1	-0.007	0.088	-10000	0	-0.3	22	22
ACTA1	-0.037	0.092	0.16	1	-0.3	34	35
NUMA1	-0.002	0.085	-10000	0	-0.31	20	20
SPTAN1	-0.044	0.092	0.2	5	-0.29	37	42
LIMK1	0.011	0.11	0.19	79	-0.34	16	95
BIRC3	0.031	0.013	-10000	0	0	81	81
BIRC2	0.036	0.005	-10000	0	0	11	11
BAX	0.033	0.01	-10000	0	0	44	44
CASP10	-0.008	0.031	0.082	47	-10000	0	47
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	-0.01	0.092	-10000	0	-0.3	28	28
DIABLO	0.036	0.004	-10000	0	0	6	6
apoptotic nuclear changes	-0.044	0.092	0.2	5	-0.29	37	42
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.036	0.006	-10000	0	0	12	12
GSN	-0.038	0.098	0.2	5	-0.31	35	40
MADD	0.036	0.006	-10000	0	0	15	15
TFAP2A	0.045	0.055	-10000	0	-0.44	5	5
BID	0	0.039	0.11	5	-0.19	16	21
MAP3K1	-0.003	0.051	-10000	0	-0.39	5	5
TRADD	0.036	0.005	-10000	0	0	11	11
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	0.099	0.2	12	-0.3	37	49
CASP9	0.034	0.009	-10000	0	0	33	33
DNA repair	0.034	0.071	0.22	32	-10000	0	32
neuron apoptosis	0.017	0.12	-10000	0	-0.62	15	15
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.025	0.088	-10000	0	-0.31	28	28
APAF1	0.036	0.003	-10000	0	0	4	4
CASP6	0.027	0.11	-10000	0	-0.84	6	6
TRAF2	0.036	0.006	-10000	0	0	15	15
ICAD/CAD	-0.047	0.084	0.22	1	-0.3	32	33
CASP7	-0.079	0.11	-10000	0	-0.24	143	143
KRT18	0.027	0.051	-10000	0	-0.46	4	4
apoptosis	-0.033	0.092	-10000	0	-0.39	13	13
DFFA	-0.043	0.087	0.17	1	-0.3	34	35
DFFB	-0.042	0.085	-10000	0	-0.3	32	32
PARP1	-0.035	0.071	-10000	0	-0.22	32	32
actin filament polymerization	-0.017	0.11	0.32	16	-0.18	79	95
TNF	0.036	0.003	-10000	0	0	4	4
CYCS	0.016	0.039	0.18	3	-0.24	3	6
SATB1	0.018	0.11	-10000	0	-0.73	6	6
SLK	-0.026	0.085	-10000	0	-0.29	33	33
p15 BID/BAX	0.002	0.06	0.15	2	-0.16	44	46
CASP2	0.062	0.1	0.22	131	-0.26	5	136
JNK cascade	0.003	0.051	0.38	5	-10000	0	5
CASP3	-0.04	0.092	-10000	0	-0.3	37	37
LMNB2	0.062	0.092	0.23	13	-0.36	4	17
RIPK1	0.035	0.007	-10000	0	0	20	20
CASP4	0.03	0.014	-10000	0	0	92	92
Mammalian IAPs/DIABLO	0.058	0.034	-10000	0	-0.15	6	6
negative regulation of DNA binding	0.045	0.054	-10000	0	-0.43	5	5
stress fiber formation	-0.036	0.085	-10000	0	-0.29	33	33
GZMB	-0.005	0.033	0.092	47	-10000	0	47
CASP1	-0.011	0.066	-10000	0	-0.2	55	55
LMNB1	0.044	0.13	0.23	14	-0.38	16	30
APP	0.017	0.12	-10000	0	-0.63	15	15
TNFRSF1A	0.032	0.012	-10000	0	0	64	64
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.011	0.002	0	13	-10000	0	13
VIM	-0.033	0.095	0.22	1	-0.36	18	19
LMNA	0.067	0.088	0.23	14	-0.36	2	16
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.018	0.056	0.16	1	-0.28	7	8
LRDD	0.035	0.007	-10000	0	0	20	20
SREBF1	-0.043	0.088	0.18	1	-0.3	34	35
APAF-1/Caspase 9	0.014	0.1	-10000	0	-0.61	12	12
nuclear fragmentation during apoptosis	-0.002	0.084	-10000	0	-0.3	20	20
CFL2	0.017	0.11	0.18	79	-0.32	16	95
GAS2	-0.033	0.092	0.19	3	-0.3	32	35
positive regulation of apoptosis	0.062	0.1	0.22	28	-0.4	6	34
PRF1	0.023	0.018	-10000	0	0	192	192

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.02	0.13	-10000	0	-0.63	18	18
epithelial cell differentiation	-0.008	0.14	-10000	0	-0.65	18	18
ITCH	0.031	0.031	0.11	1	-0.1	22	23
WWP1	-0.021	0.22	-10000	0	-1.1	18	18
FYN	0.03	0.014	-10000	0	0	90	90
EGFR	0.009	0.016	-10000	0	0	381	381
PRL	0.036	0.006	-10000	0	0	15	15
neuron projection morphogenesis	-0.028	0.11	0.24	7	-0.5	19	26
PTPRZ1	0.022	0.018	-10000	0	0	201	201
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.054	0.12	-10000	0	-0.54	18	18
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.003	0.11	-10000	0	-0.57	18	18
ADAM17	0.031	0.031	-10000	0	-0.096	24	24
ErbB4/ErbB4	0.001	0.14	0.22	7	-0.69	18	25
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.009	0.12	-10000	0	-0.62	18	18
NCOR1	0.035	0.008	-10000	0	0	26	26
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.016	0.12	-10000	0	-0.58	18	18
GRIN2B	-0.028	0.11	0.21	3	-0.55	18	21
ErbB4/ErbB2/betacellulin	0.024	0.12	0.22	1	-0.55	18	19
STAT1	0.034	0.01	-10000	0	0	40	40
HBEGF	0.035	0.008	-10000	0	0	23	23
PRLR	0.036	0.004	-10000	0	0	6	6
E4ICDs/ETO2	0.02	0.13	-10000	0	-0.63	18	18
axon guidance	-0.032	0.16	-10000	0	-0.78	18	18
NEDD4	0.029	0.031	0.11	1	-0.11	21	22
Prolactin receptor/Prolactin receptor/Prolactin	0.052	0.011	-10000	0	-10000	0	0
CBFA2T3	0.034	0.009	-10000	0	0	30	30
ErbB4/ErbB2/HBEGF	0.023	0.11	0.22	1	-0.55	18	19
MAPK3	-0.021	0.11	0.24	6	-0.52	18	24
STAT1 (dimer)	0.019	0.13	-10000	0	-0.63	18	18
MAPK1	-0.023	0.11	0.26	5	-0.52	19	24
JAK2	0.031	0.014	-10000	0	0	83	83
ErbB4/ErbB2/neuregulin 1 beta	0.003	0.11	0.21	1	-0.55	18	19
NRG1	-0.022	0.021	0.089	5	-0.083	18	23
NRG3	0	0	-10000	0	-10000	0	0
NRG2	0.036	0.005	-10000	0	0	10	10
NRG4	0	0	-10000	0	-10000	0	0
heart development	-0.032	0.16	-10000	0	-0.78	18	18
neural crest cell migration	0.003	0.11	0.21	1	-0.54	18	19
ERBB2	-0.021	0.023	0.098	8	-0.083	18	26
WWOX/E4ICDs	0.022	0.13	-10000	0	-0.62	18	18
SHC1	0.033	0.011	-10000	0	0	52	52
ErbB4/EGFR/neuregulin 4	-0.015	0.099	-10000	0	-0.48	18	18
apoptosis	-0.004	0.12	0.58	18	-10000	0	18
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.021	0.13	-10000	0	-0.63	18	18
ErbB4/ErbB2/epiregulin	0.023	0.11	-10000	0	-0.55	18	18
ErbB4/ErbB4/betacellulin/betacellulin	0.022	0.13	-10000	0	-0.63	18	18
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.062	0.13	-10000	0	-0.57	18	18
MDM2	0	0.13	0.27	13	-0.6	18	31
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.02	0.1	-10000	0	-0.51	18	18
STAT5A	-0.037	0.15	-10000	0	-0.76	18	18
ErbB4/EGFR/neuregulin 1 beta	-0.005	0.089	-10000	0	-0.43	18	18
DLG4	0.036	0.005	-10000	0	0	11	11
GRB2/SHC	0.043	0.037	-10000	0	-0.15	14	14
E4ICDs/TAB2/NCoR1	0.029	0.13	-10000	0	-0.62	18	18
STAT5A (dimer)	-0.001	0.16	-10000	0	-0.72	18	18
MAP3K7IP2	0.033	0.011	-10000	0	0	46	46
STAT5B (dimer)	-0.017	0.16	0.28	1	-0.76	18	19
LRIG1	0.03	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	9	9
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.032	0.16	-10000	0	-0.79	18	18
ERBB4	0.001	0.14	0.22	7	-0.69	18	25
STAT5B	0.036	0.004	-10000	0	0	5	5
YAP1	-0.071	0.2	-10000	0	-0.49	93	93
GRB2	0.035	0.007	-10000	0	0	17	17
ErbB4/ErbB2/neuregulin 4	0.001	0.11	-10000	0	-0.55	18	18
glial cell differentiation	-0.029	0.13	0.62	18	-10000	0	18
WWOX	0.035	0.007	-10000	0	0	17	17
cell proliferation	-0.014	0.11	0.23	1	-0.57	18	19

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.058	0.38	0.76	2	-1	26	28
STAT6 (cleaved dimer)	-0.07	0.35	-10000	0	-0.94	31	31
IGHG1	-0.015	0.26	0.43	21	-0.78	23	44
IGHG3	-0.068	0.36	0.63	1	-0.92	32	33
AKT1	-0.026	0.27	0.51	5	-0.71	33	38
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	0.014	0.19	0.45	6	-0.55	9	15
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.01	0.26	0.5	5	-0.73	22	27
THY1	-0.13	0.5	0.78	2	-1.2	62	64
MYB	0.032	0.012	-10000	0	0	58	58
HMGA1	0.036	0.005	-10000	0	0	11	11
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.003	0.26	0.52	13	-0.59	17	30
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.009	0.25	0.49	4	-0.79	16	20
SP1	0.029	0.076	0.12	71	-0.14	70	141
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.007	0.045	-10000	0	-0.078	1	1
STAT6 (dimer)/ETS1	-0.056	0.37	0.59	1	-0.94	30	31
SOCS1	-0.041	0.3	0.5	6	-0.67	32	38
SOCS3	-0.006	0.22	-10000	0	-0.69	2	2
FCER2	-0.03	0.32	0.65	1	-0.81	13	14
PARP14	0.001	0.001	-10000	0	-10000	0	0
CCL17	-0.065	0.38	0.72	1	-1	22	23
GRB2	0.035	0.007	-10000	0	0	17	17
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	0.002	0.22	0.44	11	-0.58	19	30
T cell proliferation	-0.073	0.38	0.64	3	-1	30	33
IL4R/JAK1	-0.073	0.38	0.66	1	-1	28	29
EGR2	-0.12	0.5	0.72	1	-1.3	51	52
JAK2	0.019	0.066	0.15	18	-10000	0	18
JAK3	0.035	0.016	-10000	0	-0.032	19	19
PIK3R1	0.032	0.012	-10000	0	0	63	63
JAK1	0.026	0.039	0.1	10	-10000	0	10
COL1A2	-0.11	0.48	0.53	2	-1.2	76	78
CCL26	-0.064	0.38	0.68	2	-0.96	32	34
IL4R	-0.061	0.41	0.8	3	-1.1	25	28
PTPN6	0.015	0.037	-10000	0	-0.056	12	12
IL13RA2	-0.32	0.66	0.76	3	-1.1	173	176
IL13RA1	0.023	0.067	0.15	18	-10000	0	18
IRF4	0.046	0.11	-10000	0	-10000	0	0
ARG1	-0.003	0.22	0.5	4	-0.89	10	14
CBL	-0.01	0.24	0.48	6	-0.56	17	23
GTF3A	0.048	0.034	0.12	70	-0.15	3	73
PIK3CA	0.031	0.013	-10000	0	0	80	80
IL13RA1/JAK2	0.025	0.1	0.23	13	-0.16	20	33
IRF4/BCL6	0.042	0.11	-10000	0	-10000	0	0
CD40LG	0.041	0.004	0.14	1	-10000	0	1
MAPK14	-0.007	0.24	0.48	6	-0.58	13	19
mitosis	-0.021	0.26	0.5	6	-0.66	33	39
STAT6	-0.07	0.43	0.78	6	-1.1	31	37
SPI1	0.037	0.013	0.1	2	-10000	0	2
RPS6KB1	-0.025	0.26	0.47	7	-0.65	32	39
STAT6 (dimer)	-0.07	0.43	0.79	5	-1.1	31	36
STAT6 (dimer)/PARP14	-0.084	0.38	-10000	0	-1	31	31
mast cell activation	-0.002	0.016	-10000	0	-0.041	20	20
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	0.005	0.22	0.48	4	-0.59	6	10
FRAP1	-0.026	0.27	0.51	5	-0.7	33	38
LTA	-0.068	0.38	0.72	1	-1.1	21	22
FES	0.035	0.007	-10000	0	0	17	17
T-helper 1 cell differentiation	0.067	0.42	1.1	31	-0.78	6	37
CCL11	-0.069	0.36	-10000	0	-1	23	23
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	0.009	0.22	0.5	5	-0.61	5	10
IL2RG	0.034	0.016	-10000	0	-0.032	13	13
IL10	-0.052	0.39	0.71	3	-1	22	25
IRS1	0.033	0.011	-10000	0	0	52	52
IRS2	0.03	0.014	-10000	0	0	96	96
IL4	0.022	0.18	0.52	2	-0.88	7	9
IL5	-0.067	0.38	0.72	1	-1	23	24
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.06	0.39	0.66	12	-0.9	39	51
COL1A1	0.017	0.26	0.56	14	-1	8	22
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.077	0.38	-10000	0	-1.1	26	26
IL2R gamma/JAK3	0.054	0.019	-10000	0	-10000	0	0
TFF3	-0.062	0.38	0.72	1	-1	24	25
ALOX15	-0.067	0.38	0.72	1	-1.1	21	22
MYBL1	0.03	0.014	-10000	0	0	97	97
T-helper 2 cell differentiation	-0.048	0.34	0.63	4	-0.81	33	37
SHC1	0.033	0.011	-10000	0	0	52	52
CEBPB	0.035	0.015	0.1	2	-10000	0	2
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.019	0.26	0.52	5	-0.75	22	27
mol:PI-3-4-5-P3	-0.025	0.27	0.51	5	-0.7	33	38
PI3K	-0.03	0.29	0.52	5	-0.75	33	38
DOK2	0	0	-10000	0	-10000	0	0
ETS1	0.004	0.047	-10000	0	-0.085	13	13
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	0.002	0.22	0.43	11	-0.57	22	33
ITGB3	-0.067	0.38	0.72	1	-1	22	23
PIGR	-0.055	0.38	0.71	2	-1.1	21	23
IGHE	-0.007	0.079	0.18	37	-0.18	18	55
MAPKKK cascade	0.003	0.21	0.43	12	-0.56	22	34
BCL6	0.031	0.012	-10000	0	0	69	69
OPRM1	-0.067	0.38	0.72	1	-1	22	23
RETNLB	-0.064	0.38	0.68	2	-0.96	32	34
SELP	-0.063	0.38	0.79	2	-1	22	24
AICDA	-0.066	0.36	-10000	0	-1	20	20

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.007	0.071	-10000	0	-0.29	22	22
KLHL20	0.048	0.09	0.2	61	-0.18	20	81
CYFIP2	0.031	0.013	-10000	0	0	78	78
Rac1/GDP	0.007	0.061	0.19	2	-0.26	14	16
ENAH	0.007	0.074	-10000	0	-0.31	21	21
AP1M1	0	0	-10000	0	-10000	0	0
RAP1B	0	0	0	60	0	12	72
RAP1A	0.036	0.005	-10000	0	0	11	11
CTNNB1	0.036	0.006	-10000	0	0	15	15
CDC42/GTP	-0.026	0.052	0.12	13	-0.19	24	37
ABI1/Sra1/Nap1	-0.014	0.033	-10000	0	-0.13	31	31
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.084	0.036	-10000	0	-0.13	8	8
RAPGEF1	-0.006	0.074	0.18	1	-0.28	21	22
CTNND1	0.034	0.009	-10000	0	0	32	32
regulation of calcium-dependent cell-cell adhesion	0.02	0.076	-10000	0	-0.29	23	23
CRK	0	0.076	0.2	1	-0.29	22	23
E-cadherin/gamma catenin/alpha catenin	0.061	0.035	-10000	0	-0.12	8	8
alphaE/beta7 Integrin	0.049	0.025	-10000	0	-0.14	7	7
IQGAP1	0.033	0.011	-10000	0	0	51	51
NCKAP1	0.036	0.002	-10000	0	0	2	2
Rap1/GTP/I-afadin	0.043	0.015	-10000	0	-0.1	1	1
DLG1	0.007	0.075	-10000	0	-0.3	23	23
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.035	0.044	-10000	0	-0.18	30	30
MLLT4	0.034	0.009	-10000	0	0	36	36
ARF6/GTP/NME1/Tiam1	0.036	0.033	-10000	0	-0.1	23	23
PI3K	-0.043	0.058	0.059	2	-0.23	30	32
ARF6	0.035	0.008	-10000	0	0	27	27
mol:Ca2+	0	0	0.001	69	0	27	96
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+	0.07	0.054	-10000	0	-0.14	25	25
AKT1	-0.023	0.052	0.13	7	-0.18	25	32
PIK3R1	0.032	0.012	-10000	0	0	63	63
CDH1	0.034	0.01	-10000	0	0	38	38
RhoA/GDP	0.011	0.07	0.19	3	-0.24	18	21
actin cytoskeleton organization	0.04	0.072	0.17	62	-0.14	17	79
CDC42/GDP	0.011	0.068	0.19	3	-0.24	15	18
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.012	0.049	-10000	0	-0.2	23	23
ITGB7	0.036	0.005	-10000	0	0	11	11
RAC1	0.024	0.017	-10000	0	0	173	173
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.077	0.057	-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	-0.006	0.071	0.18	3	-0.27	16	19
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	0.026	0.077	0.2	3	-0.24	19	22
RAC1/GTP/IQGAP1	0.023	0.042	-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	18	18
CDC42	0.035	0.008	-10000	0	0	24	24
CTNNA1	0.035	0.007	-10000	0	0	20	20
positive regulation of S phase of mitotic cell cycle	0.014	0.045	0.11	8	-0.12	28	36
NME1	0	0	-10000	0	0	31	31
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	0.008	0.072	-10000	0	-0.3	20	20
regulation of cell-cell adhesion	-0.028	0.04	-10000	0	-0.17	26	26
WASF2	-0.008	0.018	-10000	0	-0.071	31	31
Rap1/GTP	-0.023	0.061	0.15	19	-0.22	22	41
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.09	0.051	-10000	0	-0.13	13	13
CCND1	0.016	0.054	0.13	8	-0.15	28	36
VAV2	0.019	0.1	-10000	0	-0.52	9	9
RAP1/GDP	-0.011	0.064	0.16	17	-0.24	16	33
adherens junction assembly	0.009	0.071	-10000	0	-0.29	20	20
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.026	0.017	-10000	0	0	152	152
PIP5K1C	0.033	0.011	-10000	0	0	50	50
regulation of heterotypic cell-cell adhesion	0.068	0.047	0.2	3	-0.13	14	17
E-cadherin/beta catenin	0.006	0.02	-10000	0	-0.092	7	7
mol:GTP	0	0	0.001	63	0	31	94
SRC	0.006	0.073	-10000	0	-0.29	23	23
PIK3CA	0.031	0.013	-10000	0	0	80	80
Rac1/GTP	-0.007	0.07	0.18	1	-0.28	21	22
E-cadherin/beta catenin/alpha catenin	0.064	0.036	-10000	0	-0.13	10	10
ITGAE	0.035	0.007	-10000	0	0	19	19
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.02	0.077	-10000	0	-0.3	23	23

×

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

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
MAP4K1	0.016	0.11	0.26	13	-0.38	21	34
CRKL	0.019	0.1	0.22	13	-0.39	22	35
HRAS	0.034	0.1	0.25	9	-0.32	22	31
mol:PIP3	0.052	0.12	0.29	29	-0.35	20	49
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0.036	0.004	-10000	0	0	6	6
GAB1	0.025	0.11	0.24	11	-0.4	22	33
FOXO3	0.053	0.16	0.31	30	-0.36	38	68
AKT1	0.054	0.17	0.33	28	-0.39	38	66
BAD	0.047	0.16	0.31	29	-0.37	39	68
megakaryocyte differentiation	0.025	0.1	0.24	11	-0.38	20	31
GSK3B	0.047	0.17	0.32	32	-0.39	39	71
RAF1	0.023	0.091	0.23	14	-0.28	22	36
SHC1	0.033	0.011	-10000	0	0	52	52
STAT3	0.018	0.1	0.22	5	-0.4	22	27
STAT1	0.015	0.2	-10000	0	-0.87	21	21
HRAS/SPRED1	0.025	0.09	0.22	10	-0.27	23	33
cell proliferation	0.01	0.095	0.23	4	-0.38	22	26
PIK3CA	0.031	0.013	-10000	0	0	80	80
TEC	0.036	0.005	-10000	0	0	8	8
RPS6KB1	0.055	0.12	0.27	19	-0.37	21	40
HRAS/SPRED2	0.044	0.1	0.25	12	-0.28	21	33
LYN/TEC/p62DOK	0.065	0.12	-10000	0	-0.4	22	22
MAPK3	0.02	0.088	0.24	25	-0.22	18	43
STAP1	0.026	0.1	0.22	6	-0.39	22	28
GRAP2	0.034	0.009	-10000	0	0	35	35
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	0.072	0.11	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	0.28	2	-0.54	21	23
PIK3R1	0.032	0.012	-10000	0	0	63	63
CBL/CRKL/GRB2	0.053	0.11	0.27	5	-0.38	21	26
PI3K	0.061	0.13	0.3	16	-0.38	20	36
PTEN	0.026	0.017	-10000	0	0	148	148
SCF/KIT/EPO/EPOR	0.022	0.22	-10000	0	-1	21	21
MAPK8	0.009	0.095	0.23	3	-0.39	22	25
STAT3 (dimer)	0.02	0.1	0.24	7	-0.39	22	29
positive regulation of transcription	0.021	0.078	0.22	27	-0.18	18	45
mol:GDP	0.041	0.098	0.23	2	-0.34	21	23
PIK3C2B	0.025	0.1	0.24	11	-0.39	22	33
CBL/CRKL	0.041	0.11	0.26	6	-0.38	21	27
FER	0.023	0.1	0.24	6	-0.39	22	28
SH2B3	0.026	0.1	0.22	6	-0.39	22	28
PDPK1	0.046	0.12	0.28	29	-0.32	22	51
SNAI2	0.026	0.11	0.23	11	-0.4	21	32
positive regulation of cell proliferation	0.027	0.17	0.32	1	-0.66	21	22
KITLG	0.038	0.021	-10000	0	-0.051	20	20
cell motility	0.027	0.17	0.32	1	-0.66	21	22
PTPN6	0.023	0.025	-10000	0	-0.033	67	67
EPOR	0.048	0.083	-10000	0	-0.49	1	1
STAT5A (dimer)	0.032	0.14	0.3	2	-0.54	21	23
SOCS1	0.036	0.005	-10000	0	0	8	8
cell migration	-0.022	0.1	0.38	22	-0.25	7	29
SOS1	0	0	-10000	0	-10000	0	0
EPO	0.025	0.022	-10000	0	-0.036	15	15
VAV1	0.034	0.009	-10000	0	0	35	35
GRB10	0.011	0.087	0.3	4	-0.36	17	21
PTPN11	0.027	0.022	-10000	0	-0.032	56	56
SCF/KIT	0.03	0.11	0.24	6	-0.41	22	28
GO:0007205	-0.002	0.007	0.021	20	-0.022	2	22
MAP2K1	0.013	0.081	0.22	13	-0.23	22	35
CBL	0.036	0.004	-10000	0	0	7	7
KIT	0.006	0.24	-10000	0	-1.1	21	21
MAP2K2	0.018	0.093	0.28	25	-0.23	21	46
SHC/Grb2/SOS1	0.052	0.11	-10000	0	-0.36	21	21
STAT5A	0.032	0.14	0.3	2	-0.56	21	23
GRB2	0.035	0.007	-10000	0	0	17	17
response to radiation	0.027	0.11	0.23	12	-0.39	21	33
SHC/GRAP2	0.043	0.03	-10000	0	-0.14	8	8
PTPRO	0.024	0.1	0.24	11	-0.39	20	31
SH2B2	0.026	0.1	0.22	6	-0.39	22	28
DOK1	0.036	0.002	-10000	0	0	2	2
MATK	0.019	0.1	0.23	4	-0.39	22	26
CREBBP	0.051	0.045	0.13	6	-0.12	21	27
BCL2	0.04	0.13	-10000	0	-0.87	6	6

×

Aurora A signaling

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
Aurora A/GADD45A	0.023	0.057	0.16	1	-0.19	27	28
BIRC5	0.029	0.015	-10000	0	0	108	108
NFKBIA	-0.008	0.042	0.21	3	-0.18	16	19
CPEB1	0.033	0.012	-10000	0	0	57	57
AKT1	-0.006	0.033	0.24	1	-0.18	7	8
NDEL1	0.035	0.007	-10000	0	0	18	18
Aurora A/BRCA1	0.023	0.043	0.14	1	-0.15	23	24
NDEL1/TACC3	0.036	0.057	0.16	1	-0.14	37	38
GADD45A	0.031	0.013	-10000	0	0	75	75
GSK3B	0.035	0.016	0.089	25	0	40	65
PAK1/Aurora A	0.029	0.05	0.16	1	-0.16	25	26
MDM2	0.033	0.011	-10000	0	0	46	46
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.012	0.026	0.092	26	-10000	0	26
TP53	0.004	0.07	-10000	0	-0.23	33	33
DLG7	-0.004	0.043	0.12	10	-0.18	13	23
AURKAIP1	0	0	-10000	0	-10000	0	0
ARHGEF7	0.032	0.012	-10000	0	0	59	59
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.038	0.061	0.17	1	-0.15	37	38
G2/M transition of mitotic cell cycle	0.023	0.042	-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	0.074	-10000	0	-0.28	28	28
G2/M transition checkpoint	0.001	0.036	0.088	1	-0.14	24	25
mRNA polyadenylation	0.015	0.051	-10000	0	-0.13	46	46
Aurora A/CPEB	0.015	0.051	0.14	1	-0.13	46	47
Aurora A/TACC1/TRAP/chTOG	0.051	0.081	-10000	0	-0.16	50	50
BRCA1	0.036	0.006	-10000	0	0	12	12
centrosome duplication	0.029	0.049	0.16	1	-0.16	25	26
regulation of centrosome cycle	0.035	0.056	0.15	1	-0.14	37	38
spindle assembly	0.049	0.08	-10000	0	-0.16	50	50
TDRD7	0.034	0.01	-10000	0	0	40	40
Aurora A/RasGAP/Survivin	0.04	0.073	-10000	0	-0.14	59	59
CENPA	0.002	0.064	-10000	0	-0.26	25	25
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	-10000	0	-0.2	21	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	0.04	0.045	-10000	0	-0.14	27	27
RASA1	0.034	0.009	-10000	0	0	32	32
Ajuba/Aurora A	0.001	0.036	0.089	1	-0.14	24	25
mitotic prometaphase	-0.004	0.009	0.068	8	-10000	0	8
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.049	0.13	24	-0.21	19	43
TACC1	0.035	0.008	-10000	0	0	23	23
TACC3	0.032	0.012	-10000	0	0	59	59
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	0.034	0.009	-10000	0	0	34	34
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	25	52
GIT1	0.036	0.003	-10000	0	0	4	4
GIT1/beta-PIX/PAK1	0.058	0.047	-10000	0	-0.12	26	26
Importin alpha/Importin beta/TPX2	-0.012	0.026	0.092	26	-10000	0	26
PPP2R5D	0.036	0.004	-10000	0	0	5	5
Aurora A/TPX2	-0.028	0.055	0.096	4	-0.22	21	25
PAK1	0.036	0.006	-10000	0	0	15	15
CKAP5	0.034	0.01	-10000	0	0	37	37

×

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

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
BAG4	0.036	0.005	-10000	0	0	11	11
Caspase 8 (4 units)	-0.009	0.096	-10000	0	-0.24	23	23
NEF	0.002	0	-10000	0	-10000	0	0
NFKBIA	0.038	0.019	0.077	64	-10000	0	64
BIRC3	-0.025	0.029	0.18	2	-0.2	2	4
CYCS	-0.003	0.083	0.18	51	-0.26	10	61
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	-0.41	6	6
protein ubiquitination	0.013	0.065	0.21	3	-0.27	6	9
CRADD	0.036	0.006	-10000	0	0	12	12
DAXX	0.036	0.004	-10000	0	0	6	6
FAS	0.019	0.018	-10000	0	0	238	238
BID	-0.002	0.056	-10000	0	-0.27	9	9
NF-kappa-B/RelA/I kappa B alpha	0.075	0.054	-10000	0	-0.13	17	17
TRADD	0.036	0.005	-10000	0	0	11	11
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	0.075	0.055	-10000	0	-0.13	17	17
MAPK8	-0.007	0.093	-10000	0	-0.38	6	6
APAF1	0.036	0.003	-10000	0	0	4	4
TRAF1	0.035	0.008	-10000	0	0	23	23
TRAF2	0.036	0.006	-10000	0	0	15	15
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.003	0.06	-10000	0	-0.28	9	9
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.031	0.075	-10000	0	-0.29	9	9
CHUK	0.013	0.066	0.21	3	-0.29	6	9
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.041	0.082	-10000	0	-0.12	58	58
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	-0.12	41	41
CASP6	0.006	0.11	-10000	0	-0.57	7	7
CASP7	-0.032	0.14	0.27	11	-0.32	25	36
RELA	0.043	0.016	0.078	74	-10000	0	74
CASP2	0.024	0.017	-10000	0	0	169	169
CASP3	0	0.11	0.26	9	-0.36	12	21
TNFRSF1A	0.032	0.012	-10000	0	0	64	64
TNFR1A/BAG4	0.035	0.054	-10000	0	-0.14	42	42
CASP8	0.036	0.006	-10000	0	0	13	13
CASP9	0.034	0.009	-10000	0	0	33	33
MAP3K14	0.026	0.076	0.19	1	-0.3	7	8
APAF-1/Caspase 9	-0.009	0.085	0.17	9	-0.26	9	18
BCL2	-0.015	0.09	0.27	1	-0.35	5	6

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.05	0.023	-10000	0	-0.14	6	6
Necdin/E2F1	-0.018	0.085	-10000	0	-0.14	156	156
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.073	0.047	-10000	0	-0.12	23	23
NGF (dimer)/p75(NTR)/BEX1	0.011	0.063	-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	67	67
MGDIs/NGR/p75(NTR)/LINGO1	0.021	0.009	-10000	0	-10000	0	0
FURIN	0.036	0.006	-10000	0	0	12	12
proBDNF (dimer)/p75(NTR)/Sortilin	0.055	0.034	-10000	0	-0.12	2	2
LINGO1	0	0	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	0.023	0.067	-10000	0	-0.16	46	46
proBDNF (dimer)	0.032	0.012	-10000	0	0	67	67
NTRK1	0.035	0.006	-10000	0	0	16	16
RTN4R	0	0	-10000	0	-10000	0	0
neuron apoptosis	0.004	0.11	0.26	2	-0.36	29	31
IRAK1	0.035	0.007	-10000	0	0	19	19
SHC1	-0.003	0.035	0.091	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	0.069	-10000	0	-0.15	28	28
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.039	0.058	-10000	0	-0.11	54	54
MAGEH1	0.032	0.013	-10000	0	0	70	70
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.003	0.075	-10000	0	-0.11	146	146
Mammalian IAPs/DIABLO	0.057	0.035	-10000	0	-0.15	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	21	21
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	0.029	0.18	1	-0.1	6	7
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	0.004	0.054	0.22	8	-10000	0	8
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.016	0.056	-10000	0	-0.18	32	32
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.041	0.019	-10000	0	-0.12	1	1
NCSTN	0.035	0.008	-10000	0	0	28	28
mol:GTP	0.031	0.04	-10000	0	-0.11	29	29
PSENEN	0.035	0.008	-10000	0	0	28	28
mol:ceramide	-0.007	0.044	0.19	8	-10000	0	8
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.014	0.052	-10000	0	-0.27	9	9
p75(NTR)/beta APP	0.042	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	0.039	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	-0.095	5	5
MYD88	0.034	0.009	-10000	0	0	36	36
CHUK	0.025	0.017	-10000	0	0	163	163
NGF (dimer)/p75(NTR)/PKA	0.031	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	18	18
MAGE-G1/E2F1	0.026	0.005	-10000	0	-10000	0	0
NT3 (dimer)	0.035	0.008	-10000	0	0	23	23
TP53	-0.014	0.064	0.17	24	-0.2	6	30
PRDM4	-0.006	0.046	0.19	8	-10000	0	8
BDNF (dimer)	0.08	0.032	-10000	0	-10000	0	0
PIK3CA	0.031	0.013	-10000	0	0	80	80
SORT1	0.036	0.006	-10000	0	0	15	15
activation of caspase activity	0.066	0.045	-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	20	20
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	0.016	0.1	0.2	32	-0.31	16	48
DIABLO	0.036	0.004	-10000	0	0	6	6
SMPD2	-0.007	0.044	0.19	8	-10000	0	8
APH1B	0.035	0.006	-10000	0	0	16	16
APH1A	0.036	0.005	-10000	0	0	11	11
proNGF (dimer)/p75(NTR)/Sortilin	0.041	0.023	-10000	0	-0.12	4	4
PSEN1	0.033	0.011	-10000	0	0	46	46
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	0.004	0.077	0.2	18	-0.26	9	27
MAPK9	0.028	0.088	0.2	37	-0.26	9	46
APAF1	0.036	0.003	-10000	0	0	4	4
NTF3	0.035	0.008	-10000	0	0	23	23
NTF4	0	0	-10000	0	-10000	0	0
NDN	0.018	0.018	-10000	0	0	258	258
RAC1/GDP	0.017	0.019	-10000	0	-0.13	5	5
RhoA-B-C/GDP	0.049	0.073	-10000	0	-0.14	53	53
p75 CTF/Sortilin/TRAF6/NRIF	0.076	0.055	-10000	0	-0.12	32	32
RhoA-B-C/GTP	0.031	0.04	-10000	0	-0.11	29	29
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.087	0.058	-10000	0	-0.12	25	25
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.085	0.029	-10000	0	-0.12	2	2
PRKACB	0.033	0.011	-10000	0	0	50	50
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	0.013	-10000	0	0	81	81
BIRC2	0.036	0.005	-10000	0	0	11	11
neuron projection morphogenesis	-0.016	0.07	0.14	27	-0.16	29	56
BAD	0.012	0.091	0.19	26	-0.28	15	41
RIPK2	0.036	0.006	-10000	0	0	14	14
NGFR	0.031	0.013	-10000	0	0	71	71
CYCS	-0.012	0.042	0.19	5	-0.19	3	8
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	0.012	0.091	0.19	25	-0.28	14	39
BDNF (dimer)/p75(NTR)	0.041	0.023	-10000	0	-10000	0	0
PI3K	0.028	0.068	-10000	0	-0.12	71	71
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	26	26
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	0.047	-10000	0	-0.12	27	27
TRAF6	0.036	0.005	-10000	0	0	10	10
RAC1	0.024	0.017	-10000	0	0	173	173
PRKCZ	0	0	-10000	0	-10000	0	0
PLG	0.034	0.01	-10000	0	0	37	37
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	0.031	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	0.012	0.09	0.19	24	-0.27	16	40
E2F1	0.035	0.007	-10000	0	0	17	17
CASP9	0.034	0.009	-10000	0	0	33	33
IKK complex	0.037	0.067	-10000	0	-0.25	9	9
NGF (dimer)/TRKA	0.026	0.005	-10000	0	-10000	0	0
MMP7	0.027	0.016	-10000	0	0	137	137
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.07	0.051	-10000	0	-0.11	31	31
MMP3	0.035	0.007	-10000	0	0	20	20
APAF-1/Caspase 9	-0.022	0.041	-10000	0	-0.2	7	7

×

Signaling events mediated by HDAC Class III

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
EP300	0.033	0.011	-10000	0	0	49	49
HDAC4	0.035	0.009	-10000	0	0	29	29
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.003	0.041	-10000	0	-0.13	45	45
CDKN1A	-0.039	0.12	-10000	0	-0.46	37	37
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.033	0.01	-10000	0	0	44	44
FOXO3	0	0.031	0.25	6	-10000	0	6
FOXO1	0	0	-10000	0	-10000	0	0
FOXO4	0.006	0.022	-10000	0	-0.18	7	7
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.034	0.01	-10000	0	0	39	39
TAT	0.036	0.005	-10000	0	0	11	11
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	0.04	0.044	0.16	30	-0.14	3	33
HIST2H4A	0.003	0.041	0.13	45	-10000	0	45
SIRT1/FOXO3a	0.026	0.039	0.15	38	-10000	0	38
SIRT1	0.032	0.046	0.18	39	-10000	0	39
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.048	0.055	0.17	25	-0.12	14	39
SIRT1/Histone H1b	0.029	0.044	0.17	4	-0.16	5	9
apoptosis	-0.049	0.05	0.12	7	-0.17	27	34
SIRT1/PGC1A	0.031	0.042	0.14	33	-0.11	11	44
p53/SIRT1	0.043	0.089	0.33	36	-0.15	18	54
SIRT1/FOXO4	0.026	0.042	0.15	30	-0.14	9	39
FOXO1/FHL2/SIRT1	0.023	0.04	0.14	21	-0.091	20	41
HIST1H1E	0.013	0.023	-10000	0	-0.18	6	6
SIRT1/p300	0.038	0.048	0.16	32	-0.14	8	40
muscle cell differentiation	0.003	0.036	0.12	2	-0.12	32	34
TP53	0.041	0.046	0.18	43	-10000	0	43
KU70/SIRT1/BAX	0.05	0.05	0.17	27	-0.12	7	34
CREBBP	0.036	0.005	-10000	0	0	8	8
MEF2D	0.036	0.005	-10000	0	0	11	11
HIV-1 Tat/SIRT1	0.039	0.043	0.16	28	-0.14	2	30
ACSS2	0.003	0.041	0.13	45	-10000	0	45
SIRT1/PCAF/MYOD	-0.003	0.036	0.12	32	-0.12	2	34

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	0.006	0.096	-10000	0	-0.39	27	27
Crk/p130 Cas/Paxillin	-0.056	0.092	-10000	0	-0.19	113	113
JUN	-0.016	0.047	-10000	0	-0.25	11	11
HRAS	0.034	0.009	-10000	0	0	32	32
RET51/GFRalpha1/GDNF/GRB10	0.037	0.058	-10000	0	-0.12	27	27
RAP1A	0.036	0.005	-10000	0	0	11	11
FRS2	0.034	0.009	-10000	0	0	30	30
RAP1A/GDP	0.026	0.008	-10000	0	-0.13	1	1
RET51/GFRalpha1/GDNF/DOK1	0.063	0.044	-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	18	18
RAP1A/GTP	0.055	0.047	-10000	0	-0.11	1	1
GRB7	0.036	0.006	-10000	0	0	14	14
RET51/GFRalpha1/GDNF	0.063	0.044	-10000	0	-10000	0	0
MAPKKK cascade	-0.004	0.073	-10000	0	-0.18	14	14
BCAR1	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	0.038	0.045	-10000	0	-0.1	23	23
lamellipodium assembly	-0.027	0.082	-10000	0	-0.22	40	40
RET51/GFRalpha1/GDNF/SHC	0.059	0.049	-10000	0	-0.12	8	8
PIK3CA	0.031	0.013	-10000	0	0	80	80
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	-0.025	0.037	0.2	9	-10000	0	9
DOK1	0.036	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	0.041	0.22	5	-0.21	9	14
DOK5	0.029	0.015	-10000	0	0	100	100
GFRA1	0.025	0.017	-10000	0	0	161	161
MAPK8	0	0.045	-10000	0	-0.25	6	6
HRAS/GTP	0.023	0.091	-10000	0	-0.17	11	11
tube development	0.025	0.025	0.2	1	-0.096	8	9
MAPK1	-0.023	0.038	0.19	10	-10000	0	10
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.013	0.063	-10000	0	-0.22	14	14
Rac1/GDP	0.017	0.019	-10000	0	-0.13	5	5
SRC	0.036	0.006	-10000	0	0	14	14
PDLIM7	0.036	0.005	-10000	0	0	11	11
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	0.063	0.044	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok5	0.039	0.071	-10000	0	-0.11	65	65
PRKCA	0.036	0.004	-10000	0	0	6	6
HRAS/GDP	0.021	0.027	-10000	0	-0.13	15	15
CREB1	-0.031	0.095	-10000	0	-0.19	111	111
PIK3R1	0.032	0.012	-10000	0	0	63	63
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.011	0.064	-10000	0	-0.17	28	28
RET51/GFRalpha1/GDNF/Grb7	0.063	0.044	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.028	0.016	-10000	0	0	126	126
DOK4	0.035	0.006	-10000	0	0	16	16
JNK cascade	-0.016	0.047	-10000	0	-0.23	13	13
RET9/GFRalpha1/GDNF/FRS2	0.045	0.034	-10000	0	-10000	0	0
SHANK3	0	0	-10000	0	-10000	0	0
RASA1	0.034	0.009	-10000	0	0	32	32
NCK1	0.035	0.008	-10000	0	0	27	27
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.011	0.038	-10000	0	-0.17	17	17
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.024	0.091	-10000	0	-0.19	101	101
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.032	0.096	-10000	0	-0.19	108	108
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.008	0.048	-10000	0	-0.18	17	17
PI3K	-0.057	0.13	-10000	0	-0.3	56	56
SOS1	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.042	0.035	-10000	0	-0.096	8	8
GRB10	0.021	0.018	-10000	0	0	220	220
activation of MAPKK activity	0.01	0.049	-10000	0	-0.28	11	11
RET51/GFRalpha1/GDNF/FRS2	0.06	0.045	-10000	0	-10000	0	0
GAB1	0.032	0.012	-10000	0	0	59	59
IRS1	0.033	0.011	-10000	0	0	52	52
IRS2	0.03	0.014	-10000	0	0	96	96
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.008	0.056	-10000	0	-0.24	8	8
RET51/GFRalpha1/GDNF/PKC alpha	0.063	0.044	-10000	0	-10000	0	0
GRB2	0.035	0.007	-10000	0	0	17	17
PRKACA	0.035	0.008	-10000	0	0	25	25
GDNF	0.036	0.004	-10000	0	0	6	6
RAC1	0.024	0.017	-10000	0	0	173	173
RET51/GFRalpha1/GDNF/IRS1	0.056	0.056	-10000	0	-0.11	22	22
Rac1/GTP	-0.029	0.097	-10000	0	-0.26	38	38
RET9/GFRalpha1/GDNF	0.033	0.023	-10000	0	-10000	0	0
GFRalpha1/GDNF	0.037	0.025	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.019	0.024	-10000	0	-0.13	10	10
alphaV beta3 Integrin	0.059	0.048	-10000	0	-0.13	27	27
PTK2	0.006	0.088	0.24	7	-0.29	21	28
IGF1R	0.033	0.012	-10000	0	0	57	57
PI4KB	0	0	-10000	0	-10000	0	0
MFGE8	0.035	0.007	-10000	0	0	19	19
SRC	0.036	0.006	-10000	0	0	14	14
CDKN1B	0	0.094	-10000	0	-0.31	39	39
VEGFA	0	0	-10000	0	-10000	0	0
ILK	0.01	0.072	-10000	0	-0.29	25	25
ROCK1	0.036	0.006	-10000	0	0	15	15
AKT1	-0.004	0.07	0.2	1	-0.3	23	24
PTK2B	-0.004	0.072	0.18	48	-0.19	4	52
alphaV/beta3 Integrin/JAM-A	0.071	0.048	-10000	0	-0.12	21	21
CBL	0.036	0.004	-10000	0	0	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.062	0.044	-10000	0	-0.12	24	24
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.068	0.067	-10000	0	-0.13	44	44
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.007	0.057	-10000	0	-0.25	14	14
alphaV/beta3 Integrin/Syndecan-1	0.055	0.043	-10000	0	-0.12	16	16
PI4KA	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.049	0.083	-10000	0	-0.15	66	66
PI4 Kinase	0	0	-10000	0	-10000	0	0
PIK3CA	0.031	0.013	-10000	0	0	80	80
alphaV/beta3 Integrin/Osteopontin	0.047	0.07	-10000	0	-0.14	57	57
RPS6KB1	-0.044	0.066	0.23	4	-0.28	4	8
TLN1	0.029	0.015	-10000	0	0	102	102
MAPK3	0.002	0.086	-10000	0	-0.33	26	26
GPR124	0.035	0.008	-10000	0	0	24	24
MAPK1	-0.002	0.087	-10000	0	-0.34	25	25
PXN	0.036	0.004	-10000	0	0	7	7
PIK3R1	0.032	0.012	-10000	0	0	63	63
alphaV/beta3 Integrin/Tumstatin	0.063	0.043	-10000	0	-0.12	24	24
cell adhesion	0.048	0.052	-10000	0	-0.16	25	25
ANGPTL3	0.036	0.005	-10000	0	0	10	10
VEGFR2 homodimer/VEGFA homodimer/Src	0.036	0.029	-10000	0	-0.12	10	10
IGF-1R heterotetramer	0.032	0.012	-10000	0	0	57	57
Rac1/GDP	0.017	0.019	-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	0.008	-10000	0	0	23	23
RAC1	0.024	0.017	-10000	0	0	173	173
regulation of cell-matrix adhesion	0.059	0.045	-10000	0	-0.12	24	24
apoptosis	0.034	0.009	-10000	0	0	31	31
CD47	0.035	0.008	-10000	0	0	23	23
alphaV/beta3 Integrin/CD47	0.06	0.047	-10000	0	-0.13	25	25
VCL	0.025	0.017	-10000	0	0	154	154
alphaV/beta3 Integrin/Del1	0.063	0.043	-10000	0	-0.12	24	24
CSF1	0.036	0.005	-10000	0	0	8	8
PIK3C2A	0.01	0.018	-10000	0	-0.095	2	2
PI4 Kinase/Pyk2	0.026	0.041	-10000	0	-0.12	29	29
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.046	0.05	-10000	0	-0.12	28	28
FAK1/Vinculin	0.013	0.076	0.25	6	-0.24	21	27
alphaV beta3/Integrin/ppsTEM5	0.06	0.045	-10000	0	-0.12	24	24
RHOA	0.035	0.007	-10000	0	0	18	18
VTN	0.036	0.004	-10000	0	0	6	6
BCAR1	0	0	-10000	0	-10000	0	0
FGF2	0.035	0.008	-10000	0	0	25	25
F11R	-0.012	0.032	0.092	44	-10000	0	44
alphaV/beta3 Integrin/Lactadherin	0.061	0.045	-10000	0	-0.13	24	24
alphaV/beta3 Integrin/TGFBR2	0.059	0.047	-10000	0	-0.12	27	27
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.059	0.04	-10000	0	-0.11	24	24
HSP90AA1	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.046	0.049	-10000	0	-0.11	31	31
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.035	0.009	-10000	0	0	29	29
alphaV/beta3 Integrin/Pyk2	0.063	0.061	0.19	43	-0.12	28	71
SDC1	0.031	0.014	-10000	0	0	83	83
VAV3	-0.026	0.029	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	52	52
FAK1/Paxillin	0.024	0.081	0.24	7	-0.24	21	28
cell migration	-0.004	0.07	0.23	6	-0.25	16	22
ITGAV	0.034	0.009	-10000	0	0	31	31
PI3K	0.054	0.086	-10000	0	-0.14	61	61
SPP1	0.033	0.011	-10000	0	0	54	54
KDR	0.029	0.015	-10000	0	0	101	101
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	0.094	-10000	0	-0.37	25	25
Rac1/GTP	-0.025	0.035	0.18	2	-0.18	6	8
EDIL3	0.036	0.004	-10000	0	0	5	5
cell proliferation	0.058	0.046	-10000	0	-0.12	27	27

×

Insulin Pathway

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
CBL/APS/CAP	0.031	0.049	-10000	0	-0.11	23	23
TC10/GTP	0.027	0.047	-10000	0	-0.12	20	20
Insulin Receptor/Insulin/IRS1/Shp2	0.074	0.059	-10000	0	-0.13	29	29
HRAS	0.034	0.009	-10000	0	0	32	32
APS homodimer	0	0	-10000	0	-10000	0	0
GRB14	0.032	0.013	-10000	0	0	70	70
FOXO3	-0.01	0.016	0.021	2	-0.061	27	29
AKT1	-0.025	0.087	0.22	17	-0.21	24	41
INSR	0.032	0.021	-10000	0	-0.039	34	34
Insulin Receptor/Insulin	0.058	0.063	0.22	7	-0.14	34	41
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.021	0.018	-10000	0	0	220	220
SORBS1	0.025	0.017	-10000	0	0	154	154
CRK	0.035	0.008	-10000	0	0	23	23
PTPN1	-0.024	0.047	0.14	17	-0.25	8	25
CAV1	-0.012	0.037	0.16	6	-0.19	8	14
CBL/APS/CAP/Crk-II/C3G	0.05	0.053	-10000	0	-0.11	13	13
Insulin Receptor/Insulin/IRS1/NCK2	0.072	0.063	-10000	0	-0.14	32	32
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.033	0.079	-10000	0	-0.13	81	81
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.021	0.068	-10000	0	-0.36	8	8
RPS6KB1	-0.032	0.081	0.17	27	-0.2	24	51
PARD6A	0.035	0.007	-10000	0	0	20	20
CBL	0.036	0.004	-10000	0	0	7	7
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.021	0.018	-10000	0	-10000	0	0
PIK3R1	0.032	0.012	-10000	0	0	63	63
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.035	0.085	0.17	22	-0.22	26	48
HRAS/GTP	-0.036	0.033	0.034	4	-0.12	43	47
Insulin Receptor	0.031	0.021	-10000	0	-0.039	34	34
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.082	0.068	-10000	0	-0.13	34	34
PRKCI	0.023	0.091	-10000	0	-0.4	19	19
Insulin Receptor/Insulin/GRB14/PDK1	0.014	0.068	-10000	0	-0.13	75	75
SHC1	0.033	0.011	-10000	0	0	52	52
negative regulation of MAPKKK cascade	0.029	0.055	-10000	0	-0.21	1	1
PI3K	0.045	0.086	-10000	0	-0.13	81	81
NCK2	0.035	0.007	-10000	0	0	17	17
RHOQ	0.035	0.007	-10000	0	0	17	17
mol:H2O2	-0.004	0.006	-10000	0	-0.034	8	8
HRAS/GDP	0.021	0.027	-10000	0	-0.13	15	15
AKT2	-0.028	0.078	0.21	15	-0.19	14	29
PRKCZ	0.002	0.079	-10000	0	-0.39	18	18
SH2B2	0	0	-10000	0	-10000	0	0
SHC/SHIP	-0.016	0.051	0.16	25	-0.14	5	30
F2RL2	0.036	0.004	-10000	0	0	7	7
TRIP10	0.034	0.009	-10000	0	0	36	36
Insulin Receptor/Insulin/Shc	0.057	0.037	-10000	0	-0.12	8	8
TC10/GTP/CIP4/Exocyst	0.041	0.029	-10000	0	-0.12	14	14
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.072	0.046	-10000	0	-0.13	14	14
RAPGEF1	0.035	0.007	-10000	0	0	19	19
RASA1	0.034	0.009	-10000	0	0	32	32
NCK1	0.035	0.008	-10000	0	0	27	27
CBL/APS/CAP/Crk-II	0.044	0.041	-10000	0	-0.11	13	13
TC10/GDP	0.023	0.024	-10000	0	-0.13	12	12
Insulin Receptor/Insulin/SHC/GRB10	0.043	0.065	-10000	0	-0.13	30	30
INPP5D	-0.02	0.027	0.061	23	-0.11	23	46
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	52	52
p62DOK/RasGAP	0.029	0.056	-10000	0	-0.21	1	1
INS	0.034	0.022	0.097	7	-0.039	34	41
mol:PI-3-4-P2	-0.02	0.027	0.061	23	-0.11	23	46
GRB2	0.035	0.007	-10000	0	0	17	17
EIF4EBP1	-0.034	0.079	0.17	23	-0.21	24	47
PTPRA	0.034	0.016	-10000	0	-0.052	7	7
PIK3CA	0.031	0.013	-10000	0	0	80	80
TC10/GTP/CIP4	0.041	0.029	-10000	0	-0.12	14	14
PDPK1	0.036	0.004	-10000	0	0	7	7
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.014	0.052	-10000	0	-0.16	34	34
Insulin Receptor/Insulin/IRS1	0.053	0.046	-10000	0	-0.12	23	23
Insulin Receptor/Insulin/IRS3	0.046	0.031	-10000	0	-0.069	8	8
Par3/Par6	0.073	0.041	-10000	0	-0.11	16	16

×

Signaling events mediated by PRL

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
CCNE1	0.032	0.012	-10000	0	0	58	58
mol:Halofuginone	-0.001	0.029	-10000	0	-0.17	14	14
ITGA1	0	0	-10000	0	-10000	0	0
CDKN1A	-0.028	0.15	-10000	0	-0.41	59	59
PRL-3/alpha Tubulin	0.018	0.032	-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	108	108
CCNA2	-0.03	0.1	0.18	8	-0.58	13	21
TUBA1B	0	0	-10000	0	-10000	0	0
EGR1	0.002	0.056	0.11	4	-0.32	14	18
CDK2/Cyclin E1	-0.005	0.15	-10000	0	-0.37	59	59
MAPK3	-0.013	0.03	0.092	37	-10000	0	37
PRL-2 /Rab GGTase beta	0.047	0.035	-10000	0	-0.16	12	12
MAPK1	-0.01	0.032	0.092	42	-10000	0	42
PTP4A1	-0.022	0.099	0.16	4	-0.6	13	17
PTP4A3	0.031	0.013	-10000	0	0	73	73
PTP4A2	0.035	0.006	-10000	0	0	16	16
ITGB1	-0.009	0.026	0.092	27	-10000	0	27
SRC	0.036	0.006	-10000	0	0	14	14
RAC1	-0.001	0.085	-10000	0	-0.39	20	20
Rab GGTase beta/Rab GGTase alpha	0.045	0.032	-10000	0	-0.14	11	11
PRL-1/ATF-5	-0.033	0.1	0.19	6	-0.54	14	20
RABGGTA	0.034	0.01	-10000	0	0	41	41
BCAR1	-0.009	0.055	0.25	21	-10000	0	21
RHOC	-0.007	0.12	-10000	0	-0.4	35	35
RHOA	-0.008	0.13	-10000	0	-0.44	34	34
cell motility	-0.005	0.12	-10000	0	-0.4	32	32
PRL-1/alpha Tubulin	-0.034	0.095	-10000	0	-0.55	14	14
PRL-3/alpha1 Integrin	0.018	0.032	-10000	0	-0.13	21	21
ROCK1	-0.004	0.12	-10000	0	-0.4	32	32
RABGGTB	0.035	0.008	-10000	0	0	26	26
CDK2	0.034	0.01	-10000	0	0	40	40
mitosis	-0.021	0.098	0.16	4	-0.59	13	17
ATF5	0.034	0.009	-10000	0	0	36	36

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.032	0.012	-10000	0	0	58	58
SMAD2	-0.016	0.06	0.17	2	-0.24	18	20
SMAD3	0.005	0.054	-10000	0	-0.32	6	6
SMAD3/SMAD4	-0.01	0.17	-10000	0	-0.49	45	45
SMAD4/Ubc9/PIASy	0.054	0.052	-10000	0	-0.12	34	34
SMAD2/SMAD2/SMAD4	0.027	0.1	-10000	0	-0.25	28	28
PPM1A	0.034	0.009	-10000	0	0	30	30
CALM1	0.033	0.011	-10000	0	0	54	54
SMAD2/SMAD4	0	0.066	-10000	0	-0.23	22	22
MAP3K1	0.035	0.007	-10000	0	0	20	20
TRAP-1/SMAD4	0.036	0.053	-10000	0	-0.14	40	40
MAPK3	0.036	0.004	-10000	0	0	6	6
MAPK1	0.033	0.01	-10000	0	0	45	45
NUP214	0.035	0.007	-10000	0	0	18	18
CTDSP1	0.035	0.006	-10000	0	0	16	16
CTDSP2	0.033	0.012	-10000	0	0	57	57
CTDSPL	0.036	0.006	-10000	0	0	12	12
KPNB1	0.035	0.007	-10000	0	0	22	22
TGFBRAP1	0.036	0.005	-10000	0	0	10	10
UBE2I	0.036	0.004	-10000	0	0	6	6
NUP153	0.034	0.009	-10000	0	0	31	31
KPNA2	0.034	0.01	-10000	0	0	39	39
PIAS4	0.035	0.008	-10000	0	0	27	27

×

Visual signal transduction: Cones

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
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 +	0.01	0.06	-10000	0	-0.11	88	88
mol:ADP	0	0	-10000	0	-10000	0	0
GNAT2	0.036	0.005	-10000	0	0	8	8
RGS9-1/Gbeta5/R9AP	0.045	0.015	-10000	0	-0.12	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.046	0.012	-10000	0	-10000	0	0
GRK7	0	0	-10000	0	-10000	0	0
CNGB3	0.036	0.005	-10000	0	0	9	9
Cone Metarhodopsin II/X-Arrestin	0.027	0	-10000	0	-10000	0	0
mol:Ca2+	-0.014	0.056	0.092	75	-10000	0	75
Cone PDE6	0.053	0.047	-10000	0	-0.11	1	1
Cone Metarhodopsin II	0	0	-10000	0	-10000	0	0
Na + (4 Units)	0.017	0.064	-10000	0	-0.11	87	87
GNAT2/GDP	0.058	0.02	-10000	0	-0.1	1	1
GNB5	0.035	0.008	-10000	0	0	24	24
mol:GMP (4 units)	-0.011	0.032	0.18	12	-10000	0	12
Cone Transducin	0.045	0.01	-10000	0	-10000	0	0
SLC24A2	0.029	0.015	-10000	0	0	100	100
GNB3/GNGT2	0.026	0.005	-10000	0	-10000	0	0
GNB3	0.035	0.007	-10000	0	0	18	18
GNAT2/GTP	0.027	0.003	-10000	0	-10000	0	0
CNGA3	0.022	0.018	-10000	0	0	197	197
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	0.061	-10000	0	-0.12	88	88
mol:Pi	0.045	0.015	-10000	0	-0.11	1	1
Cone CNG Channel	0.026	0.075	-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	100	100
RGS9	0.035	0.007	-10000	0	0	17	17
PDE6C	0.025	0.017	-10000	0	0	155	155
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 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
BCL2L1	0.034	0.009	-10000	0	0	32	32
NFATC1	0.004	0.1	0.23	1	-0.39	23	24
NFATC2	-0.034	0.082	-10000	0	-0.16	118	118
NFATC3	0.01	0.019	-10000	0	-0.1	13	13
YWHAE	0.035	0.008	-10000	0	0	27	27
Calcineurin A alpha-beta B1/CABIN1	-0.007	0.075	0.16	2	-0.23	23	25
Exportin 1/Ran/NUP214	0.068	0.029	-10000	0	-0.15	6	6
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.02	0.089	-10000	0	-0.21	20	20
BCL2/BAX	0.047	0.023	-10000	0	-0.14	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	0.021	0.026	-10000	0	-0.13	13	13
CaM/Ca2+	0.021	0.026	-10000	0	-0.13	13	13
BAX	0.033	0.01	-10000	0	0	44	44
MAPK14	0.036	0.004	-10000	0	0	6	6
BAD	0.036	0.006	-10000	0	0	14	14
CABIN1/MEF2D	0.007	0.081	-10000	0	-0.22	22	22
Calcineurin A alpha-beta B1/BCL2	0.035	0.007	-10000	0	0	20	20
FKBP8	0.035	0.009	-10000	0	0	29	29
activation-induced cell death of T cells	-0.007	0.08	0.22	22	-10000	0	22
KPNB1	0.035	0.007	-10000	0	0	22	22
KPNA2	0.034	0.01	-10000	0	0	39	39
XPO1	0.036	0.004	-10000	0	0	5	5
SFN	0.031	0.013	-10000	0	0	78	78
MAP3K8	0.022	0.018	-10000	0	0	196	196
NFAT4/CK1 alpha	0.025	0.042	0.17	1	-0.16	16	17
MEF2D/NFAT1/Cbp/p300	0.011	0.11	0.23	1	-0.21	37	38
CABIN1	-0.007	0.075	0.16	2	-0.23	23	25
CALM1	0.033	0.011	-10000	0	0	54	54
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	9	9
mol:Ca2+	0	0.001	-10000	0	-10000	0	0
MAPK3	0.036	0.004	-10000	0	0	6	6
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	0.035	0.008	-10000	0	0	24	24
MAPK8	0.027	0.016	-10000	0	0	138	138
MAPK9	0.036	0.006	-10000	0	0	15	15
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0.033	0.01	-10000	0	0	44	44
NFAT1-c-4/YWHAQ	0.001	0.1	0.22	1	-0.35	23	24
PRKCH	0.034	0.01	-10000	0	0	43	43
CABIN1/Cbp/p300	0.047	0.028	-10000	0	-0.14	7	7
CASP3	0.034	0.009	-10000	0	0	31	31
PIM1	0.036	0.005	-10000	0	0	8	8
Calcineurin A alpha-beta B1/FKBP12/FK506	0.02	0.019	-10000	0	-0.11	10	10
apoptosis	0.02	0.035	-10000	0	-0.16	13	13
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.001	0.095	-10000	0	-0.32	25	25
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.036	0.003	-10000	0	0	4	4
JNK2/NFAT4	0.026	0.036	-10000	0	-0.12	20	20
BAD/BCL-XL	0.048	0.025	-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	158	158
FKBP38/BCL2	0.049	0.016	-10000	0	-10000	0	0
EP300	0.033	0.011	-10000	0	0	49	49
PRKCB1	0.031	0.013	-10000	0	0	82	82
CSNK2A1	0.034	0.009	-10000	0	0	31	31
NFATc/JNK1	0.013	0.099	0.24	1	-0.38	22	23
CaM/Ca2+/FKBP38	0.04	0.03	-10000	0	-0.11	13	13
FKBP12/FK506	0.022	0.023	-10000	0	-0.13	10	10
CSNK1A1	-0.016	0.021	0.087	12	-0.11	9	21
CaM/Ca2+/CAMK IV	0.041	0.029	-10000	0	-0.11	13	13
NFATc/ERK1	0.022	0.1	0.24	1	-0.37	23	24
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.019	0.091	-10000	0	-0.22	22	22
NR4A1	-0.024	0.079	0.16	9	-0.2	32	41
GSK3B	0.034	0.01	-10000	0	0	40	40
positive T cell selection	0.01	0.019	-10000	0	-0.1	13	13
NFAT1/CK1 alpha	-0.019	0.069	0.091	1	-0.12	117	118
RCH1/ KPNB1	0.036	0.057	-10000	0	-0.15	43	43
YWHAQ	0.036	0.005	-10000	0	0	9	9
PRKACA	0.035	0.008	-10000	0	0	25	25
AKAP5	0.034	0.009	-10000	0	0	31	31
MEF2D	0.036	0.005	-10000	0	0	11	11
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.035	0.007	-10000	0	0	21	21
NFATc/p38 alpha	0.022	0.1	0.24	1	-0.37	23	24
CREBBP	0.036	0.005	-10000	0	0	8	8
BCL2	0.035	0.007	-10000	0	0	20	20

×

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	0.011	-10000	0	-0.09	7	7
STMN1	-0.015	0.027	0.091	30	-10000	0	30
Aurora B/RasGAP/Survivin	0.034	0.074	-10000	0	-0.14	71	71
Chromosomal passenger complex/Cul3 protein complex	-0.032	0.076	-10000	0	-0.19	63	63
BIRC5	0.029	0.015	-10000	0	0	108	108
DES	0.028	0.078	-10000	0	-0.6	7	7
Aurora C/Aurora B/INCENP	0.062	0.022	-10000	0	-10000	0	0
Aurora B/TACC1	0.042	0.026	-10000	0	-0.11	9	9
Aurora B/PP2A	0.05	0.015	-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	20	-0.009	1	21
NDC80	-0.01	0.007	0.014	2	-10000	0	2
Cul3 protein complex	0.026	0.032	-10000	0	-0.14	8	8
KIF2C	-0.018	0.12	-10000	0	-0.46	32	32
PEBP1	-0.001	0.003	0.009	17	-0.009	10	27
KIF20A	0.028	0.015	-10000	0	0	109	109
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.04	0.044	-10000	0	-0.14	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	0.072	-10000	0	-0.46	7	7
PSMA3	0.034	0.009	-10000	0	0	35	35
G2/M transition of mitotic cell cycle	-0.001	0.002	0.008	10	-0.006	3	13
H3F3B	0.009	0.032	-10000	0	-0.2	11	11
AURKB	0.032	0.015	-10000	0	-0.009	54	54
AURKC	0.036	0.006	-10000	0	0	15	15
CDCA8	0.032	0.013	-10000	0	-0.003	58	58
cytokinesis	-0.024	0.14	0.18	7	-0.42	49	56
Aurora B/Septin1	-0.013	0.14	0.2	3	-0.39	49	52
AURKA	-0.001	0.002	0.008	10	-0.006	3	13
INCENP	0.034	0.014	0.058	1	-0.022	28	29
KLHL13	0	0	-10000	0	-10000	0	0
BUB1	0.036	0.006	0.058	1	0	11	12
hSgo1/Aurora B/Survivin	0.022	0.05	-10000	0	-0.11	56	56
EVI5	0.035	0.007	-10000	0	0	18	18
RhoA/GTP	0.012	0.13	-10000	0	-0.32	52	52
SGOL1	0	0	-10000	0	-10000	0	0
CENPA	-0.004	0.075	0.13	1	-0.28	30	31
NCAPG	0	0	-10000	0	-10000	0	0
Aurora B/HC8 Proteasome	0.045	0.029	-10000	0	-0.14	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	18	18
NCAPH	0	0	-10000	0	-10000	0	0
NPM1	0.006	0.065	-10000	0	-0.3	18	18
RASA1	0.034	0.009	-10000	0	0	32	32
KLHL9	0.021	0.018	-10000	0	0	213	213
mitotic prometaphase	-0.001	0.003	0.009	17	-0.009	10	27
proteasomal ubiquitin-dependent protein catabolic process	0.045	0.029	-10000	0	-0.14	8	8
PPP1CC	0.036	0.005	-10000	0	0	9	9
Centraspindlin	0.002	0.13	-10000	0	-0.34	51	51
RhoA/GDP	0.024	0.019	-10000	0	-0.13	7	7
NSUN2	0.003	0.037	-10000	0	-0.28	7	7
MYLK	-0.015	0.07	-10000	0	-0.2	64	64
KIF23	0.028	0.018	-10000	0	-0.006	103	103
VIM	-0.013	0.019	0.088	12	-10000	0	12
RACGAP1	0.03	0.016	-10000	0	-0.003	86	86
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.004	0.062	-10000	0	-0.28	21	21
Chromosomal passenger complex	-0.015	0.096	0.13	4	-0.27	51	55
Chromosomal passenger complex/EVI5	0.062	0.085	-10000	0	-0.15	55	55
TACC1	0.035	0.008	-10000	0	0	23	23
PPP2R5D	0.036	0.004	-10000	0	0	5	5
CUL3	0.036	0.002	-10000	0	0	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.045	-10000	0	-0.14	25	25
MAP2K4	0.015	0.059	0.21	2	-0.27	8	10
IKBKB	0.036	0.003	-10000	0	0	4	4
TNFRSF10B	0.035	0.008	-10000	0	0	26	26
TNFRSF10A	0	0	-10000	0	-10000	0	0
SMPD1	0.014	0.028	-10000	0	-0.1	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	0.044	-10000	0	-0.14	24	24
TRAIL/TRAILR3	0.035	0.045	-10000	0	-0.14	25	25
TRAIL/TRAILR1	0.015	0.035	-10000	0	-0.13	26	26
TRAIL/TRAILR4	0.035	0.045	-10000	0	-0.14	25	25
TRAIL/TRAILR1/DAP3/GTP	0.028	0.04	-10000	0	-0.1	34	34
IKK complex	-0.033	0.12	-10000	0	-0.22	132	132
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	0.024	-10000	0	-0.13	12	12
MAPK3	-0.005	0.039	0.092	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	11	11
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	0.092	68	-10000	0	68
TRAIL/TRAILR1/FADD/TRADD/RIP	0.07	0.047	-10000	0	-0.1	25	25
mol:ceramide	0.014	0.028	-10000	0	-0.1	20	20
FADD	0.036	0.006	-10000	0	0	12	12
MAPK8	0.008	0.04	0.19	1	-0.24	4	5
TRAF2	0.036	0.006	-10000	0	0	15	15
TRAILR3 (trimer)	0.036	0.006	-10000	0	0	14	14
CHUK	0.025	0.017	-10000	0	0	163	163
TRAIL/TRAILR1/FADD	0.033	0.038	-10000	0	-0.11	25	25
DAP3	0.035	0.007	-10000	0	0	22	22
CASP10	-0.004	0.051	0.14	15	-0.16	22	37
JNK cascade	0.035	0.045	-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	33	33
TRAIL/TRAILR2/FADD	0.05	0.048	-10000	0	-0.12	23	23
cell death	0.014	0.028	-10000	0	-0.1	20	20
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.024	0.05	-10000	0	-0.17	20	20
TRAILR2 (trimer)	0.035	0.008	-10000	0	0	26	26
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	0.086	0.057	-10000	0	-0.11	23	23

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.011	0.026	0.084	36	-10000	0	36
SNTA1	0.033	0.011	-10000	0	0	55	55
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.014	0.033	0.082	52	-10000	0	52
MAPK12	-0.011	0.029	0.2	3	-0.17	9	12
CCND1	-0.019	0.1	-10000	0	-0.37	39	39
p38 gamma/SNTA1	-0.01	0.038	0.2	3	-0.16	10	13
MAP2K3	0.036	0.005	-10000	0	0	10	10
PKN1	0.033	0.011	-10000	0	0	48	48
G2/M transition checkpoint	-0.011	0.029	0.2	3	-0.17	9	12
MAP2K6	-0.005	0.034	0.21	5	-0.18	10	15
MAPT	-0.025	0.077	0.16	5	-0.2	73	78
MAPK13	-0.014	0.03	0.092	36	-10000	0	36
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.01	0.031	-10000	0	-0.2	11	11

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.035	0.007	-10000	0	0	21	21
HDAC3	0.036	0.005	-10000	0	0	8	8
VDR	0.035	0.007	-10000	0	0	18	18
Cbp/p300/PCAF	0.042	0.024	-10000	0	-0.12	7	7
EP300	0.033	0.011	-10000	0	0	49	49
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.002	0.05	-10000	0	-0.2	5	5
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.036	0.004	-10000	0	0	6	6
AKT1	0.008	0.078	0.21	1	-0.25	7	8
RAR alpha/9cRA/Cyclin H	-0.024	0.12	-10000	0	-0.29	36	36
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.003	0.055	-10000	0	-0.2	20	20
CDC2	0.019	0.02	-10000	0	-0.001	241	241
response to UV	-0.001	0.007	-10000	0	-0.026	33	33
RAR alpha/Jnk1	0.023	0.028	0.16	1	-10000	0	1
NCOR2	0.036	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	0.035	0.008	-10000	0	0	27	27
NCOA1	0.033	0.011	-10000	0	0	50	50
VDR/VDR/DNA	0.035	0.007	-10000	0	0	18	18
RARG	0.032	0.017	-10000	0	-0.025	41	41
RAR gamma1/9cRA	0.046	0.012	-10000	0	-10000	0	0
MAPK3	0.032	0.018	-10000	0	-0.03	39	39
MAPK1	0.033	0.01	-10000	0	0	45	45
MAPK8	0.024	0.022	-10000	0	-0.045	21	21
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.02	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	0.006	0.038	-10000	0	-0.16	8	8
PRKCA	0.031	0.027	0.075	4	-0.072	32	36
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.029	0.16	-10000	0	-0.61	33	33
RXRG	0.019	0.028	-10000	0	-10000	0	0
RXRA	-0.011	0.082	0.15	4	-0.3	24	28
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	141	141
CRBP1/9-cic-RA	-0.004	0.06	-10000	0	-0.13	90	90
RARB	0.032	0.021	-10000	0	-0.046	32	32
PRKCG	0.031	0.027	0.074	4	-0.071	33	37
MNAT1	0.034	0.01	-10000	0	0	38	38
RAR alpha/RXRs	-0.013	0.13	0.24	1	-0.42	24	25
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.006	0.089	-10000	0	-0.3	22	22
proteasomal ubiquitin-dependent protein catabolic process	-0.007	0.056	-10000	0	-0.18	11	11
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.029	0.16	-10000	0	-0.61	33	33
positive regulation of DNA binding	-0.028	0.12	-10000	0	-0.27	37	37
NRIP1	-0.053	0.27	-10000	0	-1.1	33	33
RXRs/RARs	-0.007	0.12	-10000	0	-0.41	34	34
RXRs/RXRs/DNA/9cRA	-0.032	0.11	-10000	0	-0.36	33	33
PRKACA	0.035	0.008	-10000	0	0	25	25
CDK7	0.035	0.008	-10000	0	0	24	24
TFIIH	0.059	0.049	-10000	0	-0.16	19	19
RAR alpha/9cRA	0.022	0.087	-10000	0	-0.17	22	22
CCNH	0.035	0.007	-10000	0	0	18	18
CREBBP	0.036	0.005	-10000	0	0	8	8
RAR gamma2/9cRA	0.056	0.049	-10000	0	-0.14	18	18

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.044	0.037	-10000	0	-0.14	17	17
ATM	0.034	0.009	-10000	0	0	35	35
UBE2D3	0.036	0.006	-10000	0	0	12	12
PRKDC	0.033	0.01	-10000	0	0	44	44
ATR	0.035	0.008	-10000	0	0	25	25
UBE2L3	0.034	0.009	-10000	0	0	33	33
FANCD2	0.008	0.035	-10000	0	-0.2	14	14
protein ubiquitination	0.077	0.055	-10000	0	-0.13	21	21
XRCC5	0.036	0.005	-10000	0	0	9	9
XRCC6	0.034	0.01	-10000	0	0	39	39
M/R/N Complex	0.069	0.024	-10000	0	-0.12	4	4
MRE11A	0.036	0.004	-10000	0	0	7	7
DNA-PK	0.057	0.049	-10000	0	-0.14	22	22
FA complex/FANCD2/Ubiquitin	0.002	0.087	-10000	0	-0.29	27	27
FANCF	0.035	0.008	-10000	0	0	27	27
BRCA1	0.036	0.006	-10000	0	0	12	12
CCNE1	0.032	0.012	-10000	0	0	58	58
CDK2/Cyclin E1	0.045	0.023	-10000	0	-0.14	2	2
FANCG	0.03	0.014	-10000	0	0	85	85
BRCA1/BACH1/BARD1	0.046	0.037	-10000	0	-0.14	18	18
FANCE	0.036	0.003	-10000	0	0	4	4
FANCC	0.035	0.007	-10000	0	0	17	17
NBN	0.036	0.006	-10000	0	0	14	14
FANCA	0.035	0.007	-10000	0	0	17	17
DNA repair	-0.018	0.081	0.23	6	-0.29	17	23
BRCA1/BARD1/ubiquitin	0.046	0.037	-10000	0	-0.14	18	18
BARD1/DNA-PK	0.07	0.064	-10000	0	-0.14	34	34
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.044	0.037	0.14	17	-10000	0	17
BRCA1/BARD1/CTIP/M/R/N Complex	0.011	0.063	-10000	0	-0.22	26	26
BRCA1/BACH1/BARD1/TopBP1	0.051	0.061	-10000	0	-0.13	45	45
BRCA1/BARD1/P53	0.067	0.067	-10000	0	-0.13	46	46
BARD1/CSTF1/BRCA1	0.062	0.04	-10000	0	-0.12	17	17
BRCA1/BACH1	0.036	0.006	-10000	0	0	12	12
BARD1	0.035	0.007	-10000	0	0	20	20
PCNA	0.034	0.01	-10000	0	0	41	41
BRCA1/BARD1/UbcH5C	0.064	0.042	-10000	0	-0.13	19	19
BRCA1/BARD1/UbcH7	0.059	0.046	-10000	0	-0.13	23	23
BRCA1/BARD1/RAD51/PCNA	0.072	0.06	-10000	0	-0.13	34	34
BARD1/DNA-PK/P53	0.068	0.083	-10000	0	-0.13	57	57
BRCA1/BARD1/Ubiquitin	0.046	0.037	-10000	0	-0.14	18	18
BRCA1/BARD1/CTIP	0.04	0.058	-10000	0	-0.13	44	44
FA complex	0.012	0.059	-10000	0	-0.2	25	25
BARD1/EWS	0.044	0.038	-10000	0	-0.14	18	18
RBBP8	-0.013	0.029	0.092	34	-10000	0	34
TP53	0.031	0.013	-10000	0	0	73	73
TOPBP1	0.033	0.011	-10000	0	0	52	52
G1/S transition of mitotic cell cycle	-0.064	0.066	0.13	46	-10000	0	46
BRCA1/BARD1	0.085	0.058	-10000	0	-0.13	21	21
CSTF1	0.034	0.009	-10000	0	0	30	30
BARD1/EWS-Fli1	0.021	0.029	-10000	0	-0.13	18	18
CDK2	0.034	0.01	-10000	0	0	40	40
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.035	0.008	-10000	0	0	25	25
RAD50	0.036	0.006	-10000	0	0	13	13
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.046	0.037	-10000	0	-0.14	18	18
EWSR1	0.034	0.009	-10000	0	0	33	33

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.023	0.1	-10000	0	-0.58	10	10
SMARCC2	0.033	0.01	-10000	0	0	44	44
SMARCC1	0.034	0.009	-10000	0	0	32	32
TBX21	0.031	0.055	0.34	1	-10000	0	1
SUMO2	0.034	0.019	-10000	0	-0.03	33	33
STAT1 (dimer)	0.036	0.038	0.11	21	-0.17	13	34
FKBP4	0.034	0.009	-10000	0	0	34	34
FKBP5	0.028	0.015	-10000	0	0	117	117
GR alpha/HSP90/FKBP51/HSP90	-0.024	0.064	-10000	0	-0.18	10	10
PRL	0.04	0.058	0.54	1	-10000	0	1
cortisol/GR alpha (dimer)/TIF2	-0.042	0.12	-10000	0	-0.32	1	1
RELA	0.015	0.11	0.18	32	-0.16	125	157
FGG	-0.049	0.1	-10000	0	-0.32	2	2
GR beta/TIF2	-0.025	0.075	-10000	0	-0.22	2	2
IFNG	0.037	0.081	-10000	0	-10000	0	0
apoptosis	-0.017	0.2	0.44	26	-0.52	31	57
CREB1	0.043	0.01	-10000	0	-10000	0	0
histone acetylation	0.022	0.054	0.22	1	-0.24	1	2
BGLAP	0.04	0.061	0.3	1	-10000	0	1
GR/PKAc	0.021	0.091	-10000	0	-0.18	21	21
NF kappa B1 p50/RelA	0.03	0.18	0.3	30	-0.26	118	148
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	0.029	0.029	0.16	7	-0.09	17	24
CSF2	0.006	0.032	-10000	0	-10000	0	0
GSK3B	0.032	0.02	0.071	1	-0.03	30	31
NR1I3	-0.012	0.18	0.45	18	-0.5	19	37
CSN2	-0.046	0.089	0.26	1	-0.29	2	3
BRG1/BAF155/BAF170/BAF60A	0.064	0.073	-10000	0	-0.16	38	38
NFATC1	0.04	0.01	-10000	0	-10000	0	0
POU2F1	0.04	0.012	-10000	0	-10000	0	0
CDKN1A	-0.13	0.41	-10000	0	-1.2	60	60
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.008	0.029	27	-10000	0	27
SFN	0.031	0.013	-10000	0	0	78	78
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.011	0.068	-10000	0	-0.15	6	6
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.066	0.27	0.43	18	-0.66	71	89
JUN	0.024	0.053	0.33	4	-10000	0	4
IL4	0.035	0.053	-10000	0	-10000	0	0
CDK5R1	0.035	0.009	-10000	0	0	24	24
PRKACA	0.035	0.008	-10000	0	0	25	25
cortisol/GR alpha (monomer)/AP-1	-0.047	0.051	-10000	0	-0.24	6	6
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.005	0.073	-10000	0	-0.16	16	16
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	0.031	0.18	5	-10000	0	5
AP-1/NFAT1-c-4	0.048	0.075	0.44	2	-10000	0	2
AFP	0.025	0.066	-10000	0	-10000	0	0
SUV420H1	0.033	0.011	-10000	0	0	51	51
IRF1	-0.027	0.12	-10000	0	-0.64	14	14
TP53	-0.016	0.17	-10000	0	-0.49	57	57
PPP5C	0.034	0.01	-10000	0	0	39	39
KRT17	0.041	0.08	0.45	1	-10000	0	1
KRT14	0.031	0.067	0.33	2	-10000	0	2
TBP	0.042	0.018	-10000	0	-10000	0	0
CREBBP	0.029	0.018	-10000	0	-0.093	10	10
HDAC1	0.032	0.007	-10000	0	-10000	0	0
HDAC2	0.031	0.012	-10000	0	-10000	0	0
AP-1	0.048	0.075	0.44	2	-10000	0	2
MAPK14	0.034	0.019	-10000	0	-0.03	32	32
MAPK10	0.029	0.02	0.073	1	-0.031	25	26
MAPK11	0.031	0.02	0.071	1	-0.03	31	32
KRT5	0.041	0.078	0.45	1	-10000	0	1
interleukin-1 receptor activity	-0.001	0	-10000	0	-10000	0	0
NCOA1	0.033	0.018	0.092	2	-0.066	9	11
STAT1	0.036	0.038	0.1	21	-0.17	13	34
CGA	0.036	0.056	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.033	0.067	-10000	0	-0.35	6	6
MAPK3	0.034	0.019	0.075	2	-0.03	35	37
MAPK1	0.031	0.02	-10000	0	-0.03	30	30
ICAM1	0.029	0.14	0.33	21	-10000	0	21
NFKB1	0.016	0.11	0.17	30	-0.16	121	151
MAPK8	0.034	0.058	0.26	3	-10000	0	3
MAPK9	0.033	0.019	-10000	0	-0.03	30	30
cortisol/GR alpha (dimer)	-0.021	0.2	0.45	22	-0.53	33	55
BAX	-0.033	0.18	-10000	0	-0.82	11	11
POMC	0.032	0.074	0.48	1	-10000	0	1
EP300	0.026	0.019	-10000	0	-0.093	10	10
cortisol/GR alpha (dimer)/p53	-0.071	0.13	-10000	0	-0.42	19	19
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.069	0.24	31	-10000	0	31
SGK1	-0.016	0.06	-10000	0	-0.24	14	14
IL13	0.029	0.063	-10000	0	-10000	0	0
IL6	0.03	0.13	0.34	18	-10000	0	18
PRKACG	0.036	0.005	-10000	0	0	11	11
IL5	0.021	0.071	0.43	1	-10000	0	1
IL2	0.042	0.075	-10000	0	-10000	0	0
CDK5	0.023	0.018	-10000	0	0	192	192
PRKACB	0.033	0.011	-10000	0	0	50	50
HSP90AA1	0	0	-10000	0	-10000	0	0
IL8	-0.11	0.4	0.34	17	-0.79	125	142
CDK5R1/CDK5	0.028	0.042	-10000	0	-0.14	18	18
NF kappa B1 p50/RelA/PKAc	0.055	0.16	0.3	28	-0.21	108	136
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.038	0.1	-10000	0	-0.37	1	1
SMARCA4	0.032	0.012	-10000	0	0	63	63
chromatin remodeling	-0.037	0.11	-10000	0	-0.38	26	26
NF kappa B1 p50/RelA/Cbp	0.046	0.16	0.3	23	-0.22	112	135
JUN (dimer)	0.024	0.053	0.33	4	-10000	0	4
YWHAH	0.031	0.013	-10000	0	0	73	73
VIPR1	0.034	0.065	0.38	5	-10000	0	5
NR3C1	-0.04	0.085	-10000	0	-0.34	1	1
NR4A1	0.039	0.008	-10000	0	-10000	0	0
TIF2/SUV420H1	0.036	0.054	-10000	0	-0.14	42	42
MAPKKK cascade	-0.017	0.2	0.44	26	-0.52	31	57
cortisol/GR alpha (dimer)/Src-1	-0.05	0.12	-10000	0	-0.39	2	2
PBX1	0.04	0.011	-10000	0	-10000	0	0
POU1F1	0.041	0.011	-10000	0	-10000	0	0
SELE	0.026	0.13	0.34	2	-10000	0	2
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.037	0.11	-10000	0	-0.38	26	26
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.038	0.1	-10000	0	-0.37	1	1
mol:cortisol	-0.034	0.061	-10000	0	-10000	0	0
MMP1	0.038	0.072	-10000	0	-0.49	3	3

×

Regulation of Telomerase

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
Telomerase catalytic core complex	0.028	0.15	-10000	0	-0.51	16	16
RAD9A	0.036	0.005	-10000	0	0	11	11
AP1	0.011	0.079	-10000	0	-0.17	70	70
IFNAR2	0.033	0.02	-10000	0	-0.035	36	36
AKT1	0.013	0.056	-10000	0	-0.25	19	19
ER alpha/Oestrogen	0.024	0.014	-10000	0	-10000	0	0
NFX1/SIN3/HDAC complex	-0.005	0.082	-10000	0	-0.26	32	32
EGF	0.033	0.016	-10000	0	-0.032	20	20
SMG5	0	0	-10000	0	-10000	0	0
SMG6	0	0	-10000	0	-10000	0	0
SP3/HDAC2	0.038	0.052	-10000	0	-0.16	20	20
TERT/c-Abl	0.035	0.16	-10000	0	-0.51	19	19
SAP18	0.034	0.01	-10000	0	0	41	41
MRN complex	0.069	0.024	-10000	0	-0.12	4	4
WT1	0.033	0.02	-10000	0	-0.035	36	36
WRN	0.035	0.009	-10000	0	0	29	29
SP1	0.033	0.023	-10000	0	-0.043	38	38
SP3	0.033	0.016	-10000	0	-0.03	25	25
TERF2IP	0.034	0.01	-10000	0	0	37	37
Telomerase/Nucleolin	0.04	0.16	-10000	0	-0.48	21	21
Mad/Max	0.047	0.028	-10000	0	-10000	0	0
TERT	0.024	0.16	-10000	0	-0.52	15	15
CCND1	-0.013	0.29	-10000	0	-0.95	39	39
MAX	0.032	0.018	-10000	0	-0.03	29	29
RBBP7	0.036	0.005	-10000	0	0	8	8
RBBP4	0.033	0.012	-10000	0	0	56	56
TERF2	0.027	0.011	0.085	4	0	52	56
PTGES3	0.036	0.006	-10000	0	0	14	14
SIN3A	0	0.001	-10000	0	-10000	0	0
Telomerase/911	0.048	0.1	-10000	0	-0.4	14	14
CDKN1B	-0.027	0.082	0.099	35	-0.34	26	61
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	39	39
SAP30	0.035	0.007	-10000	0	0	20	20
TRF2/PARP2	0.033	0.056	-10000	0	-0.14	45	45
UBE3A	0.035	0.011	-10000	0	-0.023	17	17
JUN	0.032	0.016	-10000	0	-0.03	17	17
E6	0	0.003	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.025	0.02	-10000	0	-0.13	4	4
FOS	0.024	0.02	-10000	0	-0.03	15	15
IFN-gamma/IRF1	0.034	0.069	-10000	0	-0.18	38	38
PARP2	0.035	0.007	-10000	0	0	21	21
BLM	0.029	0.015	-10000	0	0	107	107
Telomerase	0.016	0.055	0.13	2	-0.32	9	11
IRF1	0.025	0.039	-10000	0	-0.12	29	29
ESR1	0.035	0.009	-10000	0	0	29	29
KU/TER	0.047	0.029	-10000	0	-0.14	9	9
ATM/TRF2	0.044	0.027	-10000	0	-0.11	7	7
ubiquitin-dependent protein catabolic process	0.003	0.079	-10000	0	-0.26	27	27
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.003	0.081	-10000	0	-0.27	27	27
HDAC1	0.035	0.007	-10000	0	0	21	21
HDAC2	0.029	0.023	-10000	0	-0.041	33	33
ATM	0.022	0.038	0.13	38	-0.18	5	43
SMAD3	-0.014	0.028	0.09	28	-10000	0	28
ABL1	0.032	0.013	-10000	0	0	70	70
MXD1	0.034	0.016	-10000	0	-0.03	29	29
MRE11A	0.036	0.004	-10000	0	0	7	7
HUS1	0.025	0.017	-10000	0	0	166	166
RPS6KB1	0.036	0.005	-10000	0	0	9	9
TERT/NF kappa B1/14-3-3	0.043	0.17	-10000	0	-0.53	17	17
NR2F2	0.022	0.023	-10000	0	-0.03	52	52
MAPK3	-0.017	0.017	0.093	2	-10000	0	2
MAPK1	-0.014	0.022	0.095	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	14	14
EGFR	0.009	0.016	-10000	0	-0.03	1	1
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.005	0.056	-10000	0	-0.14	64	64
MYC	0.028	0.019	-10000	0	-0.029	21	21
IL2	0.034	0.023	-10000	0	-0.043	36	36
KU	0.047	0.029	-10000	0	-0.14	9	9
RAD50	0.036	0.006	-10000	0	0	13	13
HSP90AA1	0	0	-10000	0	-10000	0	0
TGFB1	0.032	0.012	-10000	0	0	66	66
TRF2/BLM	0.01	0.077	-10000	0	-0.15	92	92
FRAP1	0.035	0.007	-10000	0	0	17	17
KU/TERT	0.05	0.16	-10000	0	-0.49	18	18
SP1/HDAC2	0.042	0.045	-10000	0	-0.14	12	12
PINX1	0	0	-10000	0	-10000	0	0
Telomerase/EST1A	0.025	0.14	-10000	0	-0.45	21	21
Smad3/Myc	0.013	0.048	-10000	0	-0.12	39	39
911 complex	0.046	0.039	-10000	0	-0.12	5	5
IFNG	0.027	0.04	-10000	0	-0.12	28	28
Telomerase/PinX1	0.025	0.14	-10000	0	-0.45	21	21
Telomerase/AKT1/mTOR/p70S6K	0.022	0.093	0.22	1	-0.47	9	10
SIN3B	0.035	0.009	-10000	0	0	29	29
YWHAE	0.035	0.008	-10000	0	0	27	27
Telomerase/EST1B	0.025	0.14	-10000	0	-0.45	21	21
response to DNA damage stimulus	0.009	0.017	-10000	0	-0.08	9	9
MRN complex/TRF2/Rap1	0.077	0.071	-10000	0	-0.14	39	39
TRF2/WRN	0.034	0.045	-10000	0	-0.11	40	40
Telomerase/hnRNP C1/C2	0.025	0.14	-10000	0	-0.45	21	21
E2F1	0.033	0.02	-10000	0	-0.035	35	35
ZNFX1	0	0.001	-10000	0	-10000	0	0
PIF1	0	0	-10000	0	-10000	0	0
NCL	0.035	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

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.056	-10000	0	-0.14	42	42
ATR	0.035	0.008	-10000	0	0	25	25
NR1D1	0.014	0.065	-10000	0	-10000	0	0
ARNTL	0.032	0.02	-10000	0	-0.069	8	8
TIMELESS	0	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	-0.07	47	57
CHEK1	0.033	0.011	-10000	0	0	49	49
mol:HEME	0.01	0.027	0.07	47	-0.13	10	57
PER1	0.033	0.011	-10000	0	0	51	51
BMAL/CLOCK/NPAS2	0.056	0.075	0.23	1	-0.14	51	52
BMAL1/CLOCK	0.01	0.12	-10000	0	-0.51	18	18
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	0.07	47	-0.13	10	57
PER1/TIMELESS	0.022	0.16	-10000	0	-1	10	10
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.035	0.007	-10000	0	0	19	19

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.035	0.008	-10000	0	0	27	27
alphaV beta3 Integrin	0.044	0.042	-10000	0	-0.14	24	24
PTK2	0.012	0.11	-10000	0	-0.32	28	28
positive regulation of JNK cascade	0.021	0.09	-10000	0	-0.29	14	14
CDC42/GDP	0.036	0.12	-10000	0	-0.37	21	21
Rac1/GDP	0.028	0.099	-10000	0	-0.37	9	9
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.036	0.005	-10000	0	0	11	11
CTNNB1	0.036	0.006	-10000	0	0	15	15
CDC42/GTP	0.029	0.11	-10000	0	-0.35	14	14
nectin-3/I-afadin	0.043	0.027	-10000	0	-0.14	5	5
RAPGEF1	0.005	0.12	-10000	0	-0.36	32	32
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.005	0.13	-10000	0	-0.4	34	34
PDGFB-D/PDGFRB	0.035	0.008	-10000	0	0	27	27
TLN1	-0.006	0.058	0.16	21	-0.23	13	34
Rap1/GTP	-0.002	0.085	-10000	0	-0.27	35	35
IQGAP1	0.033	0.011	-10000	0	0	51	51
Rap1/GTP/I-afadin	0.042	0.015	-10000	0	-0.1	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.043	0.027	-10000	0	-0.14	5	5
PVR	0.034	0.009	-10000	0	0	32	32
Necl-5(dimer)	0.034	0.009	-10000	0	0	32	32
mol:GDP	0.021	0.14	-10000	0	-0.44	21	21
MLLT4	0.034	0.009	-10000	0	0	36	36
PIK3CA	0.031	0.013	-10000	0	0	80	80
PI3K	0.057	0.088	-10000	0	-0.13	64	64
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	0.019	0.078	-10000	0	-0.3	10	10
PVRL1	0.036	0.004	-10000	0	0	7	7
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	38	38
CLDN1	0.034	0.009	-10000	0	0	36	36
JAM-A/CLDN1	0.074	0.045	-10000	0	-0.11	9	9
SRC	0.012	0.14	-10000	0	-0.42	36	36
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	0.027	0.13	-10000	0	-0.51	8	8
RAC1	0.024	0.017	-10000	0	0	173	173
CTNNA1	0.035	0.007	-10000	0	0	20	20
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	0.023	0.042	-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	-0.29	14	14
alphaV/beta3 Integrin/Talin	0.031	0.087	0.22	28	-0.21	25	53
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	0.04	0.089	4	-0.22	14	18
VAV2	0.025	0.14	-10000	0	-0.49	14	14
RAP1/GDP	0.026	0.11	-10000	0	-0.34	22	22
ITGAV	0.034	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	-0.13	7	7
nectin-3(dimer)/I-afadin/I-afadin	0.043	0.027	-10000	0	-0.14	5	5
Rac1/GTP	0.024	0.094	-10000	0	-0.36	10	10
PTPRM	0.008	0.045	-10000	0	-0.22	16	16
E-cadherin/beta catenin/alpha catenin	0.084	0.057	-10000	0	-0.12	13	13
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.035	0.008	-10000	0	0	24	24

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	0.053	0.093	-10000	0	-0.2	45	45
Ran/GTP/Exportin 1/HDAC1	-0.029	0.022	-10000	0	-0.11	26	26
NF kappa B1 p50/RelA/I kappa B alpha	0.006	0.11	-10000	0	-0.26	48	48
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	33	33
Histones	0.034	0.072	-10000	0	-0.22	21	21
YY1/LSF	0.016	0.062	-10000	0	-0.22	18	18
SMG5	0	0	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	0	10	10
I kappa B alpha/HDAC3	0.001	0.076	-10000	0	-0.2	51	51
I kappa B alpha/HDAC1	0.008	0.097	-10000	0	-0.22	63	63
SAP18	0.034	0.01	-10000	0	0	41	41
RELA	-0.002	0.076	0.19	1	-0.26	16	17
HDAC1/Smad7	0.042	0.041	-10000	0	-0.12	6	6
RANGAP1	0.033	0.01	-10000	0	0	45	45
HDAC3/TR2	0.027	0.07	-10000	0	-0.25	21	21
NuRD/MBD3 Complex	-0.009	0.11	-10000	0	-0.34	36	36
NF kappa B1 p50/RelA	0.011	0.088	-10000	0	-0.29	18	18
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.035	0.007	-10000	0	0	18	18
GATA1	0.037	0	-10000	0	-10000	0	0
Mad/Max	0.051	0.013	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.007	0.11	-10000	0	-0.33	35	35
RBBP7	0.036	0.005	-10000	0	0	8	8
NPC	0.017	0.02	-10000	0	-0.087	18	18
RBBP4	0.033	0.011	-10000	0	0	56	56
MAX	0.034	0.009	-10000	0	0	32	32
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.035	0.008	-10000	0	0	25	25
NFKBIA	0.002	0.078	-10000	0	-0.21	47	47
KAT2B	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	-0.006	0.087	-10000	0	-0.29	29	29
SIN3 complex	0.056	0.041	-10000	0	-0.12	17	17
SMURF1	0.025	0.017	-10000	0	0	167	167
CHD3	0.036	0.005	-10000	0	0	11	11
SAP30	0.035	0.007	-10000	0	0	20	20
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.035	0.008	-10000	0	0	26	26
YY1/HDAC3	0	0.074	-10000	0	-0.24	29	29
YY1/HDAC2	0.016	0.056	-10000	0	-0.2	17	17
YY1/HDAC1	0.017	0.061	-10000	0	-0.22	18	18
NuRD/MBD2 Complex (MeCP1)	-0.002	0.091	-10000	0	-0.28	33	33
PPARG	0.002	0.077	-10000	0	-0.21	52	52
HDAC8/hEST1B	0.023	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	0.008	-10000	0	0	25	25
TNFRSF1A	0.032	0.012	-10000	0	0	64	64
HDAC3/SMRT (N-CoR2)	0.026	0.07	-10000	0	-0.25	21	21
MBD3L2	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.042	0.04	-10000	0	-0.12	6	6
CREBBP	0.036	0.005	-10000	0	0	8	8
NuRD/MBD3/MBD3L2 Complex	-0.003	0.1	-10000	0	-0.31	37	37
HDAC1	0.035	0.007	-10000	0	0	21	21
HDAC3	0.009	0.057	-10000	0	-0.15	45	45
HDAC2	0.032	0.012	-10000	0	0	67	67
YY1	0.01	0.028	-10000	0	-0.21	7	7
HDAC8	0	0	-10000	0	-10000	0	0
SMAD7	0.033	0.01	-10000	0	0	44	44
NCOR2	0.036	0.002	-10000	0	0	2	2
MXD1	0.036	0.003	-10000	0	0	3	3
STAT3	0.006	0.06	-10000	0	-0.21	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	0.03	0.07	-10000	0	-0.21	18	18
YY1/SAP30/HDAC1	0.032	0.068	-10000	0	-0.2	18	18
EP300	0.033	0.011	-10000	0	0	49	49
STAT3 (dimer non-phopshorylated)	0.006	0.06	-10000	0	-0.21	33	33
proteasomal ubiquitin-dependent protein catabolic process	0.002	0.077	-10000	0	-0.21	47	47
histone deacetylation	-0.003	0.092	-10000	0	-0.27	35	35
STAT3 (dimer non-phopshorylated)/HDAC3	0	0.092	-10000	0	-0.31	27	27
nuclear export	-0.023	0.005	-10000	0	-10000	0	0
PRKACA	0.035	0.008	-10000	0	0	25	25
GATAD2B	0	0	-10000	0	-10000	0	0
GATAD2A	0.033	0.011	-10000	0	0	53	53
GATA2/HDAC3	0.026	0.069	-10000	0	-0.24	21	21
GATA1/HDAC1	0.05	0.024	-10000	0	-0.14	7	7
GATA1/HDAC3	0.027	0.07	-10000	0	-0.25	21	21
CHD4	0.034	0.01	-10000	0	0	37	37
TNF-alpha/TNFR1A	0.035	0.055	-10000	0	-0.14	43	43
SIN3/HDAC complex/Mad/Max	-0.004	0.085	-10000	0	-0.26	33	33
NuRD Complex	-0.002	0.1	-10000	0	-0.33	33	33
positive regulation of chromatin silencing	0.032	0.071	-10000	0	-0.22	21	21
SIN3B	0.035	0.009	-10000	0	0	29	29
MTA2	0.036	0.004	-10000	0	0	6	6
SIN3A	0	0	-10000	0	-10000	0	0
XPO1	0.036	0.004	-10000	0	0	5	5
SUMO1/HDAC1	0.036	0.055	-10000	0	-0.14	20	20
HDAC complex	0.066	0.069	-10000	0	-0.14	40	40
GATA1/Fog1	0.027	0	-10000	0	-10000	0	0
FKBP25/HDAC1/HDAC2	0.054	0.046	-10000	0	-0.12	21	21
TNF	0.036	0.003	-10000	0	0	4	4
negative regulation of cell growth	-0.004	0.085	-10000	0	-0.26	34	34
NuRD/MBD2/PRMT5 Complex	-0.002	0.091	-10000	0	-0.28	33	33
Ran/GTP/Exportin 1	0.036	0.059	-10000	0	-0.16	21	21
NF kappa B/RelA/I kappa B alpha	-0.006	0.093	-10000	0	-0.25	51	51
SIN3/HDAC complex/NCoR1	-0.003	0.088	-10000	0	-0.31	25	25
TFCP2	0.035	0.008	-10000	0	0	25	25
NR2C1	0.036	0.004	-10000	0	0	5	5
MBD3	0.034	0.01	-10000	0	0	43	43
MBD2	0.035	0.007	-10000	0	0	17	17

×

Arf6 trafficking events

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
SLC2A4	0.036	0.005	-10000	0	0	11	11
CLTC	0.013	0.087	-10000	0	-0.32	25	25
calcium ion-dependent exocytosis	0.017	0.067	0.13	1	-0.21	20	21
Dynamin 2/GTP	0.026	0.011	0.08	1	-0.1	1	2
EXOC4	0	0	-10000	0	-10000	0	0
CD59	0.004	0.079	-10000	0	-0.28	27	27
CPE	-0.015	0.009	-10000	0	-0.11	1	1
CTNNB1	0.036	0.006	-10000	0	0	15	15
membrane fusion	0.019	0.066	0.099	118	-0.17	31	149
CTNND1	-0.019	0.011	0.086	1	-0.18	1	2
DNM2	0.035	0.009	-10000	0	0	29	29
mol:PI-4-5-P2	0.011	0.066	0.15	8	-0.22	18	26
TSHR	-0.016	0.009	0.091	1	-0.11	1	2
INS	0.012	0.081	-10000	0	-0.44	14	14
BIN1	0.031	0.013	-10000	0	0	77	77
mol:Choline	0.019	0.066	0.099	118	-0.17	31	149
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	0.008	-10000	0	0	27	27
mol:Ca2+	0.025	0.011	0.079	1	-0.1	1	2
JUP	0.012	0.069	-10000	0	-0.27	21	21
ASAP2/amphiphysin II	0.028	0.045	-10000	0	-0.1	48	48
ARF6/GTP	0.025	0.009	-10000	0	-0.13	1	1
CDH1	0.009	0.071	-10000	0	-0.26	24	24
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	0.005	0.052	-10000	0	-0.3	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	0.076	0.27	22	-10000	0	22
positive regulation of phagocytosis	-0.015	0.007	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.046	0.014	-10000	0	-0.12	1	1
ACAP1	0.02	0.063	-10000	0	-0.22	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.004	0.062	-10000	0	-0.3	14	14
clathrin heavy chain/ACAP1	0.017	0.084	0.2	9	-0.23	28	37
JIP4/KLC1	0.036	0.035	-10000	0	-0.1	26	26
EXOC1	0.033	0.011	-10000	0	0	50	50
exocyst	0.003	0.051	-10000	0	-0.31	5	5
RALA/GTP	0.013	0.03	-10000	0	-0.13	17	17
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.038	0.038	-10000	0	-0.12	26	26
receptor recycling	0.025	0.009	-10000	0	-0.13	1	1
CTNNA1	-0.019	0.011	0.086	1	-0.18	1	2
NME1	-0.009	0.005	-10000	0	-0.11	1	1
clathrin coat assembly	0.012	0.087	-10000	0	-0.32	25	25
IL2RA	0.007	0.067	-10000	0	-0.32	14	14
VAMP3	-0.015	0.007	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.032	0.082	-10000	0	-0.23	28	28
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	-0.001	0.043	-10000	0	-0.21	15	15
PLD2	-0.001	0.043	-10000	0	-0.21	15	15
EXOC5	0.03	0.014	-10000	0	0	85	85
PIP5K1C	0.009	0.062	0.12	3	-0.21	19	22
SDC1	0.014	0.073	-10000	0	-0.26	24	24
ARF6/GDP	0.026	0.006	-10000	0	0	27	27
EXOC7	0.036	0.005	-10000	0	0	10	10
E-cadherin/beta catenin	0.041	0.079	-10000	0	-0.28	22	22
mol:Phosphatidic acid	0.019	0.066	0.099	118	-0.17	31	149
endocytosis	-0.027	0.044	0.1	48	-10000	0	48
SCAMP2	0.034	0.009	-10000	0	0	31	31
ADRB2	0.011	0.086	0.23	1	-0.31	24	25
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	0.089	1	-0.1	1	2
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	0.005	0.083	-10000	0	-0.31	25	25
RALA	0.024	0.018	-10000	0	0	180	180
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.021	0.084	0.22	1	-0.26	27	28

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.027	0.078	-10000	0	-0.24	23	23
CaM/Ca2+	0.021	0.026	-10000	0	-0.13	13	13
AKT1	0.033	0.011	-10000	0	0	53	53
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	0.006	0.075	0.17	2	-0.26	23	25
YWHAZ	0.035	0.007	-10000	0	0	21	21
CALM1	0.033	0.011	-10000	0	0	54	54
YWHAQ	0.036	0.005	-10000	0	0	9	9
TBC1D4	-0.016	0.021	0.092	16	-10000	0	16
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.031	0.013	-10000	0	0	73	73
YWHAB	0.035	0.008	-10000	0	0	24	24
SNARE/Synip	0.021	0.017	-10000	0	-0.11	8	8
YWHAG	0	0	-10000	0	-10000	0	0
ASIP	0.036	0.006	-10000	0	0	15	15
PRKCI	0.035	0.008	-10000	0	0	26	26
AS160/CaM/Ca2+	0.021	0.026	-10000	0	-0.13	13	13
RHOQ	0.035	0.007	-10000	0	0	17	17
GYS1	0.002	0.041	0.24	4	-0.21	6	10
PRKCZ	0	0	-10000	0	-10000	0	0
TRIP10	0.034	0.009	-10000	0	0	36	36
TC10/GTP/CIP4/Exocyst	0.041	0.029	-10000	0	-0.12	14	14
AS160/14-3-3	-0.005	0.098	-10000	0	-0.4	19	19
VAMP2	0.033	0.011	-10000	0	0	48	48
SLC2A4	0.005	0.081	0.17	2	-0.28	23	25
STX4	0	0	-10000	0	-10000	0	0
GSK3B	0.004	0.076	-10000	0	-0.3	27	27
SFN	0.031	0.013	-10000	0	0	78	78
LNPEP	0.036	0.005	-10000	0	0	8	8
YWHAE	0.035	0.008	-10000	0	0	27	27

×

Ceramide signaling pathway

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
SPHK2	-0.008	0.033	0.092	47	-10000	0	47
MAP4K4	0.004	0.051	-10000	0	-0.21	9	9
BAG4	0.036	0.005	-10000	0	0	11	11
PKC zeta/ceramide	0.003	0.05	-10000	0	-0.23	14	14
NFKBIA	0.033	0.012	-10000	0	0	57	57
BIRC3	0.031	0.013	-10000	0	0	81	81
BAX	0.001	0.078	-10000	0	-0.3	27	27
RIPK1	0.035	0.007	-10000	0	0	20	20
AKT1	-0.012	0.04	0.47	2	-10000	0	2
BAD	-0.004	0.05	-10000	0	-0.24	13	13
SMPD1	-0.003	0.052	0.13	3	-0.18	21	24
RB1	-0.004	0.051	0.21	1	-0.24	14	15
FADD/Caspase 8	0.014	0.05	-10000	0	-0.24	4	4
MAP2K4	-0.007	0.054	0.17	5	-0.23	14	19
NSMAF	0.035	0.009	-10000	0	0	29	29
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.01	0.054	0.2	7	-0.24	13	20
EGF	0.035	0.008	-10000	0	0	25	25
mol:ceramide	0.004	0.054	-10000	0	-0.25	14	14
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	0.034	0.092	51	-10000	0	51
ASAH1	0.035	0.007	-10000	0	0	17	17
negative regulation of cell cycle	-0.003	0.051	0.2	1	-0.24	14	15
cell proliferation	0.019	0.056	0.18	4	-0.22	6	10
BID	0.004	0.15	-10000	0	-0.59	26	26
MAP3K1	-0.001	0.053	0.13	4	-0.24	14	18
EIF2A	-0.01	0.052	0.2	5	-0.22	15	20
TRADD	0.036	0.005	-10000	0	0	11	11
CRADD	0.036	0.006	-10000	0	0	12	12
MAPK3	-0.006	0.051	0.18	11	-0.23	6	17
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.014	0.064	0.18	10	-0.22	22	32
Cathepsin D/ceramide	0.019	0.059	-10000	0	-0.24	14	14
FADD	0.009	0.045	-10000	0	-0.23	3	3
KSR1	-0.004	0.051	-10000	0	-0.24	14	14
MAPK8	-0.04	0.095	0.18	1	-0.19	114	115
PRKRA	-0.006	0.054	0.23	2	-0.23	15	17
PDGFA	0.027	0.016	-10000	0	0	134	134
TRAF2	0.036	0.006	-10000	0	0	15	15
IGF1	0.035	0.008	-10000	0	0	23	23
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	0.004	0.054	-10000	0	-0.24	14	14
CTSD	0.033	0.011	-10000	0	0	55	55
regulation of nitric oxide biosynthetic process	0.049	0.025	-10000	0	-0.14	7	7
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.021	0.06	0.2	4	-0.24	6	10
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	0.034	0.092	51	-10000	0	51
RelA/NF kappa B1	0.049	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	15	15
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.018	0.054	-10000	0	-0.24	6	6
TNFR1A/BAG4/TNF-alpha	0.053	0.056	-10000	0	-0.12	41	41
mol:Sphingosine-1-phosphate	-0.008	0.033	0.092	47	-10000	0	47
MAP2K1	-0.016	0.053	0.18	8	-0.23	13	21
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.036	0.005	-10000	0	0	9	9
CYCS	0.024	0.064	0.14	21	-0.16	23	44
TNFRSF1A	0.032	0.012	-10000	0	0	64	64
NFKB1	0.035	0.007	-10000	0	0	18	18
TNFR1A/BAG4	0.035	0.054	-10000	0	-0.14	42	42
EIF2AK2	-0.011	0.055	0.21	5	-0.23	15	20
TNF-alpha/TNFR1A/FAN	0.047	0.066	-10000	0	-0.13	54	54
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.033	0.051	-10000	0	-0.26	5	5
MAP2K2	-0.008	0.053	0.18	20	-0.22	5	25
SMPD3	0.006	0.056	0.15	2	-0.28	9	11
TNF	0.036	0.003	-10000	0	0	4	4
PKC zeta/PAR4	0.026	0.005	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.005	0.045	0.13	7	-0.14	18	25
NF kappa B1/RelA/I kappa B alpha	0.07	0.047	-10000	0	-0.12	20	20
AIFM1	-0.004	0.052	0.13	3	-0.16	34	37
BCL2	0.035	0.007	-10000	0	0	20	20

×

Calcium signaling in the CD4+ TCR pathway

Figure S108. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S108. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.003	0.036	0.096	25	-0.1	10	35
NFATC2	-0.001	0.027	0.078	19	-0.096	10	29
NFATC3	-0.003	0.038	0.098	25	-0.1	10	35
CD40LG	0.015	0.12	0.29	41	-0.24	1	42
PTGS2	-0.017	0.073	0.34	3	-10000	0	3
JUNB	0.031	0.014	-10000	0	0	83	83
CaM/Ca2+/Calcineurin A alpha-beta B1	0.026	0.026	0.083	1	-0.12	12	13
CaM/Ca2+	0.026	0.026	0.083	1	-0.12	12	13
CALM1	0.035	0.013	0.07	1	-10000	0	1
JUN	0.036	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	0.022	0.02	-10000	0	-0.11	10	10
FOSL1	0.033	0.011	-10000	0	0	55	55
CREM	0.026	0.016	-10000	0	0	142	142
Jun/NFAT1-c-4/p21SNFT	0.057	0.069	0.26	12	-0.18	3	15
FOS	0.027	0.019	-10000	0	-10000	0	0
IFNG	0.014	0.11	0.35	19	-0.24	1	20
AP-1/NFAT1-c-4	0.093	0.11	0.35	10	-0.26	1	11
FASLG	0.014	0.12	0.29	37	-0.24	1	38
NFAT1-c-4/ICER1	0.041	0.052	0.21	10	-10000	0	10
IL2RA	0.005	0.088	0.26	19	-0.24	1	20
FKBP12/FK506	0.022	0.023	-10000	0	-0.13	10	10
CSF2	0.015	0.12	0.34	20	-10000	0	20
JunB/Fra1/NFAT1-c-4	0.057	0.061	0.22	9	-0.18	1	10
IL4	0.015	0.12	0.29	37	-0.24	1	38
IL2	0.012	0.087	-10000	0	-0.84	5	5
IL3	0.03	0.085	-10000	0	-0.58	9	9
FKBP1A	0.033	0.01	-10000	0	0	44	44
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

×

IL27-mediated signaling events

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
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	0.001	0.067	0.5	2	-10000	0	2
IL27/IL27R/JAK1	0.04	0.062	-10000	0	-10000	0	0
TBX21	-0.014	0.093	0.34	19	-10000	0	19
IL12B	0.037	0.005	-10000	0	0	9	9
IL12A	-0.011	0.002	0.002	14	-10000	0	14
IL6ST	0.034	0.011	-10000	0	-0.033	1	1
IL27RA/JAK1	0.027	0.048	-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	0.064	0.083	0.18	153	-0.13	6	159
T-helper 2 cell differentiation	0.001	0.067	0.5	2	-10000	0	2
T cell proliferation during immune response	0.001	0.067	0.5	2	-10000	0	2
MAPKKK cascade	-0.001	0.067	-10000	0	-0.5	2	2
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	23	23
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.015	0.091	0.34	18	-10000	0	18
IL27/IL27R/JAK2/TYK2	-0.002	0.067	-10000	0	-0.51	2	2
positive regulation of T cell mediated cytotoxicity	-0.001	0.067	-10000	0	-0.5	2	2
STAT1 (dimer)	0.048	0.08	-10000	0	-10000	0	0
JAK2	0.03	0.014	-10000	0	-0.032	1	1
JAK1	0.033	0.01	-10000	0	0	41	41
STAT2 (dimer)	0.015	0.099	-10000	0	-0.49	2	2
T cell proliferation	0.003	0.061	-10000	0	-10000	0	0
IL12/IL12R/TYK2/JAK2	0.006	0.18	-10000	0	-0.76	26	26
IL17A	0.062	0.082	0.18	146	-0.13	6	152
mast cell activation	0.001	0.067	0.5	2	-10000	0	2
IFNG	0.003	0.029	-10000	0	-0.09	17	17
T cell differentiation	-0.001	0.003	-10000	0	-0.017	8	8
STAT3 (dimer)	0.011	0.11	-10000	0	-0.4	9	9
STAT5A (dimer)	0.016	0.1	-10000	0	-0.49	2	2
STAT4 (dimer)	0.015	0.098	-10000	0	-0.49	2	2
STAT4	0.035	0.009	-10000	0	0	29	29
T cell activation	-0.005	0.005	-10000	0	-0.085	1	1
IL27R/JAK2/TYK2	0.039	0.062	-10000	0	-10000	0	0
GATA3	0.007	0.092	0.67	9	-10000	0	9
IL18	-0.01	0.004	0	72	-10000	0	72
positive regulation of mast cell cytokine production	0.011	0.11	-10000	0	-0.4	9	9
IL27/EBI3	0.025	0.011	-10000	0	-10000	0	0
IL27RA	0.001	0.025	-10000	0	-10000	0	0
IL6	0.019	0.018	-10000	0	0	238	238
STAT5A	0.036	0.004	-10000	0	0	5	5
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.007	0.031	-10000	0	-10000	0	0
IL1B	-0.009	0.005	0	101	-10000	0	101
EBI3	0.034	0.012	-10000	0	-0.033	1	1
TNF	-0.011	0.001	0	4	-10000	0	4

×

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	0.062	0.03	-9999	-0.12	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	38	38

×

Coregulation of Androgen receptor activity

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
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	-0.044	1	1
JMJD2C	0.036	0.014	-10000	0	-10000	0	0
T-DHT/AR/Ubc9	0.052	0.041	-10000	0	-0.079	32	32
CARM1	0.035	0.009	-10000	0	0	29	29
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	0.011	-10000	0	-0.001	54	54
PTK2B	0.036	0.007	-10000	0	-10000	0	0
MED1	0	0	-10000	0	-10000	0	0
MAK	0.033	0.008	-10000	0	-0.044	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	0.034	0.01	-10000	0	-10000	0	0
DNA-PK	0.055	0.049	-10000	0	-0.14	22	22
NCOA4	0.027	0.016	-10000	0	0	139	139
PIAS3	0.036	0.006	-10000	0	-10000	0	0
cell proliferation	0.022	0.049	-10000	0	-0.43	5	5
XRCC5	0.036	0.005	-10000	0	0	9	9
UBE3A	0.037	0.003	-10000	0	-10000	0	0
T-DHT/AR/SNURF	0.031	0.033	0.12	1	-0.071	33	34
FHL2	0.018	0.2	-10000	0	-0.68	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	176	176
TGFB1I1	0.033	0.012	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	0.034	0.056	-10000	0	-0.12	30	30
XRCC6	0.033	0.01	-10000	0	0	39	39
T-DHT/AR	0.048	0.059	0.22	1	-0.13	33	34
CTDSP1	0.036	0.006	-10000	0	-10000	0	0
CTDSP2	0.031	0.012	-10000	0	-0.042	1	1
BRCA1	0.036	0.006	-10000	0	-10000	0	0
TCF4	0.031	0.012	-10000	0	-0.038	1	1
CDKN2A	0.004	0.012	-10000	0	0	444	444
SRF	0.04	0.055	0.11	90	-0.15	33	123
NKX3-1	0.025	0.07	-10000	0	-0.28	21	21
KLK3	0.016	0.046	-10000	0	-10000	0	0
TMF1	0.035	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	0.035	0.03	-10000	0	-0.068	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	15	15
PRKDC	0.033	0.01	-10000	0	0	44	44
PA2G4	0.034	0.007	-10000	0	-0.034	1	1
UBE2I	0.036	0.004	-10000	0	0	6	6
T-DHT/AR/Cyclin D3/CDK11 p58	0.045	0.044	-10000	0	-0.086	22	22
RPS6KA3	0.036	0.007	-10000	0	-10000	0	0
T-DHT/AR/ARA70	0.039	0.046	-10000	0	-0.11	4	4
LATS2	-0.001	0	-10000	0	-10000	0	0
T-DHT/AR/PRX1	0.046	0.043	-10000	0	-0.079	39	39
Cyclin D3/CDK11 p58	0.021	0.028	-10000	0	-0.13	16	16
VAV3	0.029	0.015	-10000	0	-10000	0	0
KLK2	0.026	0.051	-10000	0	-0.32	8	8
CASP8	0.035	0.006	-10000	0	0	13	13
T-DHT/AR/TIF2/CARM1	0.07	0.046	-10000	0	-0.11	1	1
TMPRSS2	0.025	0.071	-10000	0	-0.3	15	15
CCND1	0.029	0.015	-10000	0	-10000	0	0
PIAS1	0.036	0.008	-10000	0	-10000	0	0
mol:T-DHT	0.004	0.017	0.051	1	-0.049	33	34
CDC2L1	0	0	-10000	0	-10000	0	0
PIAS4	0.036	0.009	-10000	0	-10000	0	0
T-DHT/AR/CDK6	0.036	0.04	-10000	0	-0.08	17	17
CMTM2	0	0	-10000	0	-10000	0	0
SNURF	0	0	-10000	0	-10000	0	0
ZMIZ1	0.004	0.017	0.051	1	-0.049	33	34
CCND3	0.035	0.008	-10000	0	0	26	26
TGIF1	-0.001	0	-10000	0	-10000	0	0
FKBP4	0.035	0.009	-10000	0	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	-0.008	0.14	0.32	19	-1	8	27
VDR	0.035	0.007	-10000	0	0	18	18
FAM120B	0	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.013	0.098	0.25	2	-0.28	38	40
RXRs/LXRs/DNA/Oxysterols	0.005	0.14	0.3	2	-0.4	45	47
MED1	0	0	-10000	0	-10000	0	0
mol:9cRA	0	0.016	0.046	3	-0.048	45	48
RARs/THRs/DNA/Src-1	0.016	0.053	-10000	0	-0.15	41	41
RXRs/NUR77	0.079	0.064	-10000	0	-0.12	32	32
RXRs/PPAR	0.02	0.047	-10000	0	-0.18	6	6
NCOR2	0.036	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	0.082	0.022	-10000	0	-10000	0	0
RARA	0.036	0.003	-10000	0	0	3	3
NCOA1	0.033	0.011	-10000	0	0	50	50
VDR/VDR/DNA	0.035	0.007	-10000	0	0	18	18
RARs/RARs/DNA/9cRA	0.056	0.032	-10000	0	-10000	0	0
RARG	0.036	0.005	-10000	0	0	8	8
RPS6KB1	-0.004	0.087	0.51	8	-0.4	8	16
RARs/THRs/DNA/SMRT	0.03	0.024	-10000	0	-0.17	5	5
THRA	0.036	0.005	-10000	0	0	11	11
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	0.084	0.1	0.31	2	-0.22	36	38
NR1H2	0.029	0.031	0.09	2	-0.062	45	47
NR1H3	0.03	0.033	0.091	2	-0.069	44	46
RXRs/VDR/DNA/Vit D3	0.072	0.061	-10000	0	-0.11	32	32
NR4A1	0.036	0.006	-10000	0	0	12	12
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.016	0.039	0.13	1	-0.14	6	7
RXRG	0.03	0.03	0.088	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	1	-0.061	44	45
RXRB	0.031	0.033	0.09	1	-0.067	48	49
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	-0.53	12	12
mol:Oxysterols	0	0.015	0.046	3	-0.042	49	52
cholesterol transport	0.005	0.14	0.3	2	-0.4	45	47
PPARA	0.033	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	0.029	-10000	0	-0.16	1	1
SREBF1	-0.01	0.17	0.34	2	-0.51	38	40
RXRs/RXRs/DNA/9cRA	0.058	0.074	0.28	3	-0.16	39	42
ABCA1	-0.043	0.26	0.34	2	-0.84	45	47
RARs/THRs	0.1	0.024	-10000	0	-0.12	1	1
RXRs/FXR	0.08	0.065	0.22	1	-0.12	34	35
BCL2	0.035	0.007	-10000	0	0	20	20

×

Atypical NF-kappaB pathway

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
BCL3/RelA	0.049	0.019	-10000	0	-0.14	2	2
FBXW11	0.035	0.008	-10000	0	0	25	25
NF kappa B1 p50/c-Rel	0.033	0.018	-10000	0	-0.12	5	5
NF kappa B1 p50/RelA/I kappa B alpha	0.022	0.067	0.16	1	-0.19	28	29
NFKBIA	0.002	0.056	-10000	0	-0.18	28	28
MAPK14	0.036	0.004	-10000	0	0	6	6
NF kappa B1 p105/p50	0.028	0.03	-10000	0	-0.13	16	16
ARRB2	0.012	0.025	-10000	0	-0.2	7	7
REL	0.036	0.003	-10000	0	0	3	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.031	0.019	-10000	0	-0.12	5	5
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.032	0.02	-10000	0	-0.12	7	7
PIK3CA	0.031	0.013	-10000	0	0	80	80
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	0.092	4	-10000	0	4
RELA	0.036	0.005	-10000	0	0	9	9
positive regulation of anti-apoptosis	0.013	0.038	0.14	2	-0.13	22	24
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.023	0.071	0.17	1	-0.25	15	16
SRC	0.036	0.006	-10000	0	0	14	14
PI3K	0.019	0.075	-10000	0	-0.16	73	73
NF kappa B1 p50/RelA	0.013	0.038	0.14	2	-0.13	22	24
IKBKB	0.036	0.003	-10000	0	0	4	4
beta TrCP1/SCF ubiquitin ligase complex	0.035	0.008	-10000	0	0	25	25
SYK	0.031	0.013	-10000	0	0	76	76
I kappa B alpha/PIK3R1	0.014	0.07	-10000	0	-0.21	32	32
cell death	0.022	0.069	0.16	1	-0.24	15	16
NF kappa B1 p105/c-Rel	0.033	0.018	-10000	0	-0.12	5	5
LCK	0.035	0.007	-10000	0	0	17	17
BCL3	0.034	0.009	-10000	0	0	34	34

×

Regulation of Androgen receptor activity

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
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	-0.007	4	4
HDAC7	-0.029	0.057	0.16	7	-0.21	19	26
JUN	0.034	0.01	-10000	0	0	40	40
EP300	0.033	0.011	-10000	0	0	49	49
KAT2B	0	0	-10000	0	-10000	0	0
KAT5	0	0	-10000	0	-10000	0	0
MAPK14	-0.017	0.019	0.089	4	-10000	0	4
FOXO1	0	0	-10000	0	-10000	0	0
T-DHT/AR	0.02	0.078	0.23	4	-0.22	19	23
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	0.014	-10000	0	-0.033	16	16
SMARCA2	0.032	0.013	-10000	0	0	67	67
PDE9A	-0.013	0.2	-10000	0	-0.79	29	29
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	-0.022	0.086	0.31	2	-0.29	17	19
NR0B1	0.03	0.014	-10000	0	0	88	88
EGR1	0.029	0.015	-10000	0	0	107	107
RXRs/9cRA	0.067	0.019	-10000	0	-0.11	1	1
AR/RACK1/Src	-0.02	0.052	0.17	12	-0.22	2	14
AR/GR	0.003	0.06	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	0.035	0.006	-10000	0	0	16	16
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	-0.012	0.02	0.094	6	-10000	0	6
T-DHT/AR/TIF2/CARM1	0.016	0.055	0.2	5	-0.19	4	9
SRC	-0.021	0.034	0.16	8	-10000	0	8
NR3C1	0.035	0.008	-10000	0	0	24	24
KLK3	-0.003	0.073	-10000	0	-0.41	1	1
APPBP2	0.034	0.015	-10000	0	-0.033	16	16
TRIM24	0.023	0.018	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.023	0.028	0.081	2	-0.15	9	11
TMPRSS2	0.016	0.085	-10000	0	-0.55	8	8
RXRG	0.036	0.006	-10000	0	0	13	13
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	0.035	0.007	-10000	0	0	19	19
RXRB	0.037	0.002	-10000	0	0	1	1
CARM1	0.035	0.009	-10000	0	0	29	29
NR2C2	0.036	0.005	-10000	0	0	8	8
KLK2	-0.006	0.041	0.19	1	-0.25	1	2
AR	-0.004	0.043	0.14	5	-0.2	17	22
SENP1	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
MDM2	0.032	0.011	-10000	0	-0.001	47	47
SRY	0.036	0.004	-10000	0	-0.009	4	4
GATA2	0.035	0.007	-10000	0	0	18	18
MYST2	0.034	0.01	-10000	0	0	37	37
HOXB13	0.037	0.003	-10000	0	-10000	0	0
T-DHT/AR/RACK1/Src	-0.022	0.053	0.17	18	-0.23	2	20
positive regulation of transcription	0.035	0.007	-10000	0	0	18	18
DNAJA1	0.031	0.017	-10000	0	-0.033	16	16
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.037	-10000	0	-0.26	8	8
NCOA1	0.038	0.023	0.14	3	-0.18	2	5
SPDEF	0.037	0.004	-10000	0	0	5	5
T-DHT/AR/TIF2	-0.031	0.084	0.17	4	-0.25	40	44
T-DHT/AR/Hsp90	-0.023	0.028	0.081	2	-0.14	10	12
GSK3B	0.034	0.01	-10000	0	0	40	40
NR2C1	0.036	0.004	-10000	0	0	5	5
mol:T-DHT	-0.019	0.031	0.15	7	-0.12	3	10
SIRT1	0.024	0.017	-10000	0	0	171	171
ZMIZ2	-0.001	0.001	-10000	0	-0.016	1	1
POU2F1	0.037	0.035	0.12	13	-0.11	22	35
T-DHT/AR/DAX-1	-0.021	0.036	0.16	2	-0.18	4	6
CREBBP	0.036	0.005	-10000	0	0	8	8
SMARCE1	0.037	0.004	-10000	0	0	6	6

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.06	0.038	-10000	0	-0.11	20	20
HDAC3	0.036	0.005	-10000	0	0	8	8
Ran/GTP/Exportin 1/HDAC4	-0.03	0.022	-10000	0	-0.1	35	35
GATA1/HDAC4	0.047	0.034	-10000	0	-0.14	15	15
GATA1/HDAC5	0.053	0.012	-10000	0	-0.14	1	1
GATA2/HDAC5	0.051	0.016	-10000	0	-0.14	1	1
HDAC5/BCL6/BCoR	0.052	0.051	-10000	0	-0.13	28	28
HDAC9	0.021	0.018	-10000	0	0	210	210
Glucocorticoid receptor/Hsp90/HDAC6	0.044	0.028	-10000	0	-0.12	14	14
HDAC4/ANKRA2	0.044	0.04	-10000	0	-0.14	20	20
HDAC5/YWHAB	0.048	0.028	-10000	0	-0.16	7	7
NPC/RanGAP1/SUMO1/Ubc9	0.007	0.034	-10000	0	-0.15	21	21
GATA2	0.035	0.007	-10000	0	0	18	18
HDAC4/RFXANK	0.038	0.049	-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	-0.16	39	39
ADRBK1	0.036	0.006	-10000	0	0	13	13
HDAC4	0.035	0.009	-10000	0	0	29	29
XPO1	0.036	0.004	-10000	0	0	5	5
HDAC5/ANKRA2	0.049	0.025	-10000	0	-0.14	7	7
HDAC4/Ubc9	0.046	0.034	-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	0.038	-10000	0	-0.14	18	18
CAMK4	0.036	0.005	-10000	0	0	9	9
Tubulin/HDAC6	0.036	0.043	-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	0.035	0.008	-10000	0	0	24	24
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	0.008	-10000	0	0	24	24
SUMO1/HDAC4	0.033	0.058	-10000	0	-0.23	6	6
SRF	0.037	0.002	-10000	0	0	1	1
HDAC4/YWHAB	0.043	0.042	-10000	0	-0.15	20	20
Tubulin	0.015	0.042	-10000	0	-0.13	38	38
HDAC4/14-3-3 E	0.042	0.044	-10000	0	-0.14	24	24
GNB1	0.035	0.007	-10000	0	0	20	20
RANGAP1	0.033	0.01	-10000	0	0	45	45
BCL6/BCoR	0.036	0.047	-10000	0	-0.14	28	28
HDAC4/HDAC3/SMRT (N-CoR2)	0.065	0.036	-10000	0	-0.12	15	15
HDAC4/SRF	0.065	0.035	-10000	0	-0.12	14	14
HDAC4/ER alpha	0.044	0.035	-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	-0.16	39	39
cell motility	0.036	0.043	-10000	0	-0.11	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	0.003	-10000	0	-10000	0	0
BCL6	0.032	0.013	-10000	0	0	69	69
HDAC4/CaMK II delta B	0.034	0.009	-10000	0	0	29	29
Hsp90/HDAC6	0.027	0	-10000	0	-10000	0	0
ESR1	0.035	0.009	-10000	0	0	29	29
HDAC6/HDAC11	0.054	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.036	0.059	-10000	0	-0.16	21	21
NPC	0.017	0.02	-10000	0	-0.087	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	0.054	-10000	0	-0.12	25	25
GNG2	0	0	-10000	0	-10000	0	0
NCOR2	0.036	0.002	-10000	0	0	2	2
TUBB2A	0.033	0.011	-10000	0	0	47	47
HDAC11	0.036	0.004	-10000	0	0	7	7
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	14	14
RFXANK	0.034	0.01	-10000	0	0	42	42
nuclear import	-0.029	0.058	0.21	26	-10000	0	26

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.009	0.034	0.14	28	-0.22	2	30
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	-0.009	0.046	0.12	2	-0.17	9	11
AP2	0.021	0.027	-10000	0	-0.13	15	15
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.027	0.036	-10000	0	-0.12	15	15
CLTB	0.036	0.005	-10000	0	0	11	11
coatomer protein complex/ARF1/GTP/ER cargo protein	0.014	0.031	-10000	0	-0.18	11	11
CD4	0.031	0.013	-10000	0	0	72	72
CLTA	0.034	0.01	-10000	0	0	42	42
mol:GTP	-0.003	0.002	0.006	1	-0.019	6	7
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	0.017	-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	0.11	8	-10000	0	8
ARF1/GDP	0.007	0.011	-10000	0	-0.078	4	4
AP2M1	0.034	0.01	-10000	0	0	37	37
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.012	0.017	0.066	1	-0.11	9	10
Rac/GTP	0.016	0.02	-10000	0	-0.14	5	5
ARF1/GTP/GGA3/ARF-GAP1	0.041	0.025	-10000	0	-0.1	8	8
ARFIP2	0.032	0.014	-10000	0	-0.038	13	13
COPA	0.036	0.006	-10000	0	0	13	13
RAC1	0.024	0.017	-10000	0	0	173	173
ARF1/GTP/coatomer protein complex	0.005	0.044	-10000	0	-0.14	34	34
ARF1/GTP/ARHGAP10	0.021	0.015	-10000	0	-0.11	6	6
GGA3	0.036	0.004	-10000	0	0	7	7
ARF1/GTP/Membrin	0.028	0.025	-10000	0	-0.24	3	3
AP2A1	0	0	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.005	0.036	-10000	0	-0.17	13	13
ARF1/GDP/Membrin	0.031	0.028	-10000	0	-0.27	3	3
Arfaptin 2/Rac/GDP	0.027	0.035	-10000	0	-0.12	15	15
CYTH2	-0.003	0.002	0.006	1	-0.019	6	7
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	0.019	-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	31	31
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	0.036	-10000	0	-0.11	8	8
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	0.023	-10000	0	-0.31	2	2
USO1	0.002	0.006	0.036	10	-0.03	4	14
GBF1	-0.075	0.15	-10000	0	-0.31	140	140
ARF1/GTP/Arfaptin 2	0.041	0.033	-10000	0	-0.12	17	17
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.031	0.046	-10000	0	-0.12	35	35

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.033	0.02	0.077	8	-0.076	13	21
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.003	0.079	-10000	0	-0.25	18	18
ERC1	0	0	-10000	0	-10000	0	0
RIP2/NOD2	0.026	0.011	-10000	0	-0.13	2	2
NFKBIA	-0.033	0.046	0.2	1	-0.28	14	15
BIRC2	0.036	0.005	-10000	0	0	11	11
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	0.072	-10000	0	-0.26	8	8
NEMO/A20/RIP2	0.036	0.006	-10000	0	0	14	14
XPO1	0.036	0.004	-10000	0	0	5	5
NEMO/ATM	0.04	0.054	-10000	0	-0.26	10	10
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	0.022	-10000	0	-0.14	6	6
IKK complex/ELKS	0.029	0.052	-10000	0	-0.24	8	8
BCL10/MALT1/TRAF6	0.063	0.034	-10000	0	-0.12	10	10
NOD2	0	0	-10000	0	-10000	0	0
NFKB1	0.034	0.02	0.077	9	-0.073	13	22
RELA	0.034	0.02	0.077	9	-0.072	15	24
MALT1	0.034	0.009	-10000	0	0	32	32
cIAP1/UbcH5C	0.05	0.027	-10000	0	-0.18	6	6
ATM	0.034	0.009	-10000	0	0	35	35
TNF/TNFR1A	0.035	0.055	-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	163	163
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	20	20
proteasomal ubiquitin-dependent protein catabolic process	-0.033	0.046	0.2	1	-0.27	14	15
beta TrCP1/SCF ubiquitin ligase complex	0.033	0.021	0.077	8	-0.057	18	26
TNFRSF1A	0.032	0.012	-10000	0	0	64	64
IKK complex	0.041	0.06	-10000	0	-0.25	8	8
CYLD	0.036	0.006	-10000	0	0	15	15
IKK complex/PKC alpha	0.051	0.066	-10000	0	-0.25	8	8

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.035	0.006	-10000	0	0	16	16
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	-0.069	0.16	-10000	0	-0.34	135	135
MAP2K2	0.018	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	0.041	0.082	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	0.011	-10000	0	0	54	54
negative regulation of phagocytosis	-0.018	0.12	-10000	0	-0.41	41	41
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	0.067	7	-10000	0	7
TNF	0.036	0.003	-10000	0	0	4	4
VCAM1	-0.069	0.16	-10000	0	-0.34	134	134
platelet activation	-0.018	0.12	-10000	0	-0.41	41	41
MAPKKK cascade	0.003	0.02	0.064	3	-0.07	30	33
IL18	-0.005	0.035	0.12	4	-0.076	60	64
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	12	-10000	0	12
mol:cAMP	-0.018	0.12	-10000	0	-0.41	41	41
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 events mediated by the Hedgehog family

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
TGFB2	0.034	0.032	-10000	0	-10000	0	0
IHH	0.051	0.012	-10000	0	-10000	0	0
SHH Np/Cholesterol/GAS1	0.014	0.027	-10000	0	-0.11	15	15
LRPAP1	0.035	0.007	-10000	0	0	18	18
dorsoventral neural tube patterning	-0.014	0.026	0.11	15	-10000	0	15
SMO/beta Arrestin2	0.09	0.065	0.26	14	-10000	0	14
SMO	0.025	0.031	-10000	0	-10000	0	0
AKT1	-0.009	0.13	-10000	0	-0.48	23	23
ARRB2	0.035	0.008	-10000	0	0	26	26
BOC	0	0	-10000	0	-10000	0	0
ADRBK1	0.036	0.006	-10000	0	0	13	13
heart looping	0.026	0.033	0.23	2	-10000	0	2
STIL	0.053	0.094	0.19	154	-10000	0	154
DHH N/PTCH2	0.027	0.003	-10000	0	-10000	0	0
DHH N/PTCH1	0.016	0.02	-10000	0	-10000	0	0
PIK3CA	0.031	0.013	-10000	0	0	80	80
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	0.033	0.23	2	-10000	0	2
PIK3R1	0.032	0.012	-10000	0	0	63	63
skeletal system development	0.038	0.047	-10000	0	-10000	0	0
IHH N/Hhip	0.033	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	0.033	0.23	2	-10000	0	2
pancreas development	0	0	-10000	0	-10000	0	0
HHAT	0.035	0.007	-10000	0	0	20	20
PI3K	0.019	0.075	-10000	0	-0.16	73	73
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.03	0.014	-10000	0	0	87	87
somite specification	0.026	0.033	0.23	2	-10000	0	2
SHH Np/Cholesterol/PTCH1	0.017	0.023	0.16	1	-10000	0	1
SHH Np/Cholesterol/PTCH2	0.02	0.016	-10000	0	-10000	0	0
SHH Np/Cholesterol/Megalin	0.02	0.016	-10000	0	-10000	0	0
SHH	-0.014	0.012	0.092	1	-10000	0	1
catabolic process	0.02	0.025	0.14	22	-10000	0	22
SMO/Vitamin D3	0.023	0.04	0.19	19	-10000	0	19
SHH Np/Cholesterol/Hhip	-0.01	0.008	-10000	0	-10000	0	0
LRP2	0.036	0.006	-10000	0	0	13	13
receptor-mediated endocytosis	0.022	0.038	0.27	2	-10000	0	2
SHH Np/Cholesterol/BOC	-0.01	0.008	-10000	0	-10000	0	0
SHH Np/Cholesterol/CDO	0.02	0.016	-10000	0	-10000	0	0
mesenchymal cell differentiation	0.01	0.008	-10000	0	-10000	0	0
mol:Vitamin D3	0.079	0.089	0.2	173	-10000	0	173
IHH N/PTCH2	0.061	0.011	-10000	0	-10000	0	0
CDON	0.036	0.005	-10000	0	0	8	8
IHH N/PTCH1	0.046	0.028	-10000	0	-10000	0	0
Megalin/LRPAP1	0.048	0.029	-10000	0	-0.14	10	10
PTCH2	0.036	0.005	-10000	0	0	8	8
SHH Np/Cholesterol	0.011	0.009	-10000	0	-10000	0	0
PTCH1	0.02	0.025	0.14	22	-10000	0	22
HHIP	0	0	-10000	0	-10000	0	0

×

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	0.005	0.081	-10000	0	-0.3	16	16
BAG4	0.036	0.005	-10000	0	0	11	11
BAD	-0.004	0.033	0.1	3	-0.14	10	13
NFKBIA	0.033	0.012	-10000	0	0	57	57
BIRC3	0.031	0.013	-10000	0	0	81	81
BAX	0.002	0.045	0.19	15	-0.14	8	23
EnzymeConsortium:3.1.4.12	0.004	0.021	0.061	2	-0.084	7	9
IKBKB	-0.005	0.08	0.2	3	-0.29	15	18
MAP2K2	-0.007	0.054	0.18	27	-0.17	5	32
MAP2K1	-0.014	0.04	0.17	6	-0.17	6	12
SMPD1	0.003	0.029	0.1	1	-0.12	13	14
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.012	0.076	-10000	0	-0.32	8	8
MAP2K4	-0.007	0.034	0.15	3	-0.14	5	8
protein ubiquitination	-0.006	0.08	-10000	0	-0.31	13	13
EnzymeConsortium:2.7.1.37	-0.013	0.048	0.17	9	-0.18	5	14
response to UV	0	0	0.002	9	-0.002	1	10
RAF1	-0.01	0.038	0.18	5	-0.15	9	14
CRADD	0.036	0.006	-10000	0	0	12	12
mol:ceramide	0.003	0.032	0.11	1	-0.13	10	11
I-kappa-B-alpha/RELA/p50/ubiquitin	0.039	0.033	-10000	0	-0.11	18	18
MADD	0.035	0.006	-10000	0	0	15	15
MAP3K1	-0.002	0.033	0.15	2	-0.14	7	9
TRADD	0.036	0.005	-10000	0	0	11	11
RELA/p50	0.036	0.005	-10000	0	0	9	9
MAPK3	-0.006	0.048	0.17	10	-0.17	4	14
MAPK1	-0.012	0.057	0.18	8	-0.2	13	21
p50/RELA/I-kappa-B-alpha	0.043	0.038	-10000	0	-0.14	18	18
FADD	0.009	0.073	-10000	0	-0.3	7	7
KSR1	-0.004	0.031	0.11	1	-0.15	6	7
MAPK8	-0.01	0.029	0.16	2	-0.15	3	5
TRAF2	0.036	0.006	-10000	0	0	15	15
response to radiation	0	0	0.002	1	-10000	0	1
CHUK	-0.008	0.074	-10000	0	-0.3	13	13
TNF R/SODD	0.035	0.054	-10000	0	-0.14	42	42
TNF	0.036	0.003	-10000	0	0	4	4
CYCS	0.017	0.052	0.15	22	-0.14	9	31
IKBKG	-0.006	0.078	-10000	0	-0.3	14	14
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.015	0.083	-10000	0	-0.34	10	10
RELA	0.036	0.005	-10000	0	0	9	9
RIPK1	0.035	0.007	-10000	0	0	20	20
AIFM1	-0.004	0.039	0.12	15	-0.13	12	27
TNF/TNF R/SODD	0.053	0.055	-10000	0	-0.12	41	41
TNFRSF1A	0.032	0.012	-10000	0	0	64	64
response to heat	0	0	0.002	1	-10000	0	1
CASP8	0.036	0.079	-10000	0	-0.55	8	8
NSMAF	0.008	0.082	0.21	5	-0.31	14	19
response to hydrogen peroxide	0	0	0.002	9	-0.002	1	10
BCL2	0.035	0.007	-10000	0	0	20	20

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	0.047	0.064	-10000	0	-10000	0	0
MKNK1	0.034	0.009	-10000	0	0	34	34
MAPK14	0.047	0.036	0.16	3	-10000	0	3
ATF2/c-Jun	0.002	0.091	-10000	0	-0.32	30	30
MAPK11	0.044	0.038	0.16	3	-0.082	20	23
MITF	0.032	0.048	0.22	1	-0.2	7	8
MAPKAPK5	0.034	0.038	0.22	1	-10000	0	1
KRT8	0.036	0.039	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	0.063	0.055	0.23	3	-10000	0	3
CEBPB	0.024	0.069	0.22	2	-0.21	27	29
SLC9A1	0.032	0.04	-10000	0	-0.26	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.032	0.054	0.26	4	-0.26	2	6
p38alpha-beta/MNK1	0.066	0.067	-10000	0	-0.14	17	17
JUN	-0.002	0.088	-10000	0	-0.32	29	29
PPARGC1A	0.032	0.056	0.29	1	-0.21	13	14
USF1	0.028	0.037	0.18	3	-10000	0	3
RAB5/GDP/GDI1	0.014	0.076	-10000	0	-0.22	26	26
NOS2	0.028	0.037	0.18	3	-10000	0	3
DDIT3	0.029	0.061	0.22	1	-0.19	20	21
RAB5A	0.034	0.009	-10000	0	0	32	32
HSPB1	0.086	0.13	0.28	144	-0.15	3	147
p38alpha-beta/HBP1	0.053	0.057	0.23	1	-10000	0	1
CREB1	0.024	0.069	0.22	1	-0.23	2	3
RAB5/GDP	0.019	0.034	-10000	0	-0.13	24	24
EIF4E	-0.015	0.056	0.21	7	-0.2	6	13
RPS6KA4	0.034	0.038	0.22	1	-10000	0	1
PLA2G4A	-0.014	0.052	0.2	4	-0.19	10	14
GDI1	0.025	0.059	0.22	1	-0.23	17	18
TP53	0.01	0.05	0.17	10	-10000	0	10
RPS6KA5	0.035	0.04	0.22	1	-0.19	1	2
ESR1	0.032	0.037	0.22	1	-10000	0	1
HBP1	0.025	0.017	-10000	0	0	163	163
MEF2C	0.032	0.048	0.19	2	-0.22	7	9
MEF2A	0.031	0.046	0.22	1	-0.21	6	7
EIF4EBP1	0.021	0.073	0.22	1	-0.34	3	4
KRT19	0.036	0.039	0.21	2	-10000	0	2
ELK4	0.031	0.036	0.16	2	-10000	0	2
ATF6	0.033	0.037	-10000	0	-10000	0	0
ATF1	0.019	0.072	0.22	1	-0.3	2	3
p38alpha-beta/MAPKAPK2	0.07	0.055	-10000	0	-10000	0	0
p38alpha-beta/MAPKAPK3	0.073	0.056	0.23	1	-0.13	2	3

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.035	0.007	-10000	0	0	21	21
Ran/GTP/Exportin 1/HDAC4	-0.032	0.03	-10000	0	-0.13	35	35
MDM2/SUMO1	0.034	0.053	-10000	0	-0.21	6	6
HDAC4	0.035	0.009	-10000	0	0	29	29
Ran/GTP/Exportin 1/HDAC1	-0.031	0.03	-10000	0	-0.14	26	26
SUMO1	0.036	0.003	-10000	0	0	4	4
NPC/RanGAP1/SUMO1	0.005	0.034	-10000	0	-0.15	22	22
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	-0.008	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	0.058	-10000	0	-0.23	6	6
SUMO1/HDAC1	0.036	0.055	-10000	0	-0.14	20	20
RANGAP1	0.033	0.01	-10000	0	0	45	45
MDM2/SUMO1/SUMO1	0.077	0.047	-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	0.033	0.011	-10000	0	0	46	46
UBE2I	0.036	0.004	-10000	0	0	6	6
Ran/GTP/Exportin 1	0.013	0.051	0.2	1	-0.16	21	22
NPC	0.017	0.02	-10000	0	-0.087	18	18
PIAS2	0.035	0.007	-10000	0	0	18	18
PIAS1	0.035	0.008	-10000	0	0	27	27
EntrezGene:9972	0	0	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.033	0.027	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	-0.014	0.016	-10000	0	-10000	0	0
mol:DAG	-0.019	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	0.04	0.19	1	-0.19	1	2
HIF1A	0.04	0.013	-10000	0	-10000	0	0
GAB1	0.032	0.012	-10000	0	0	59	59
AKT1	-0.032	0.087	0.2	7	-0.3	24	31
PLCG1	-0.019	0.032	0.19	1	-10000	0	1
NOS3	0.008	0.066	-10000	0	-0.3	7	7
CBL	0.036	0.004	-10000	0	0	7	7
mol:NO	0.013	0.072	-10000	0	-0.3	7	7
FLT1	0.016	0.008	-10000	0	-10000	0	0
PGF	0.031	0.013	-10000	0	0	71	71
VEGFR1 homodimer/NRP2/VEGFR121	0.03	0.025	-10000	0	-10000	0	0
CALM1	0.033	0.011	-10000	0	0	54	54
PIK3CA	0.031	0.013	-10000	0	0	80	80
eNOS/Hsp90	0.001	0.068	-10000	0	-0.29	7	7
endothelial cell proliferation	-0.006	0.048	-10000	0	-0.31	3	3
mol:Ca2+	-0.019	0.032	0.19	1	-10000	0	1
MAPK3	-0.027	0.033	0.15	4	-10000	0	4
MAPK1	-0.027	0.035	0.15	2	-0.19	1	3
PIK3R1	0.032	0.012	-10000	0	0	63	63
PLGF homodimer	0.031	0.013	-10000	0	0	71	71
PRKACA	0.035	0.008	-10000	0	0	25	25
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.016	0.018	-10000	0	0	290	290
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	-0.028	0.045	0.21	1	-10000	0	1
PI3K	0.037	0.077	-10000	0	-0.2	15	15
PRKCA	-0.024	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	-10000	0	0
VEGFA	0	0	-10000	0	-10000	0	0
VEGFB	0.036	0.005	-10000	0	0	8	8
mol:IP3	-0.019	0.032	0.19	1	-10000	0	1
RASA1	-0.026	0.026	0.19	1	-0.2	5	6
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	0.005	-10000	0	0	8	8
NCK1	0.035	0.008	-10000	0	0	27	27
eNOS/Caveolin-1	0.002	0.069	-10000	0	-0.29	11	11
PTPN11	0.036	0.005	-10000	0	0	11	11
mol:PI-3-4-5-P3	0.035	0.076	-10000	0	-0.2	15	15
mol:L-citrulline	0.013	0.072	-10000	0	-0.3	7	7
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.041	0.043	-10000	0	-0.19	3	3
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.028	0.028	-10000	0	-0.19	1	1
CD2AP	0.034	0.01	-10000	0	0	41	41
PI3K/GAB1	0.041	0.087	-10000	0	-0.2	20	20
PDPK1	-0.03	0.066	0.24	4	-0.26	2	6
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.029	0.029	-10000	0	-0.19	1	1
mol:NADP	0.013	0.072	-10000	0	-0.3	7	7
HSP90AA1	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.039	0.042	-10000	0	-0.18	3	3
VEGFR1 homodimer/NRP2	0.032	0.028	-10000	0	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	-0.054	0.018	-10000	0	-10000	0	0
KIRREL	0.038	0.01	-10000	0	-0.041	1	1
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.054	0.018	-10000	0	-10000	0	0
PLCG1	0.035	0.007	-10000	0	0	19	19
ARRB2	0.035	0.008	-10000	0	0	26	26
WASL	0.024	0.017	-10000	0	0	172	172
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	0.015	0.036	-10000	0	-0.23	5	5
FYN	-0.008	0.046	0.18	24	-10000	0	24
mol:Ca2+	0.086	0.037	0.19	1	-0.12	3	4
mol:DAG	0.087	0.037	0.2	1	-0.12	3	4
NPHS2	0.039	0.008	-10000	0	-0.041	1	1
mol:IP3	0.087	0.037	0.2	1	-0.12	3	4
regulation of endocytosis	0.052	0.05	-10000	0	-0.13	4	4
Nephrin/NEPH1/podocin/Cholesterol	0.07	0.028	0.16	8	-10000	0	8
establishment of cell polarity	0.054	0.018	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2	0.096	0.058	-10000	0	-0.14	16	16
Nephrin/NEPH1/beta Arrestin2	0.055	0.051	-10000	0	-0.13	4	4
NPHS1	0.039	0.01	0.077	7	-10000	0	7
Nephrin/NEPH1/podocin	0.053	0.044	0.21	1	-0.1	1	2
TJP1	0.034	0.01	-10000	0	0	38	38
NCK1	0.035	0.008	-10000	0	0	27	27
NCK2	0.035	0.007	-10000	0	0	17	17
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.089	0.038	0.2	1	-0.12	3	4
CD2AP	0.034	0.01	-10000	0	0	41	41
Nephrin/NEPH1/podocin/GRB2	0.087	0.043	0.2	1	-0.12	7	8
GRB2	0.035	0.007	-10000	0	0	17	17
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.014	0.049	0.18	25	-10000	0	25
cytoskeleton organization	-0.009	0.036	0.17	9	-0.22	3	12
Nephrin/NEPH1	0.046	0.016	-10000	0	-10000	0	0
Nephrin/NEPH1/ZO-1	0.064	0.038	-10000	0	-0.14	9	9

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	0.037	0.028	-9999	0	-0.095	20	20
MAPK9	0.007	0.001	-9999	0	0	15	15
adrenocorticotropin secretion	-0.011	0.002	0	17	-10000	0	17
GNB1/GNG2	0.02	0.025	-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	6	6
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	0.035	0.007	-9999	0	0	17	17
mol:cortisol	0	0	-9999	0	-10000	0	0
MAPK8	0.006	0.003	-9999	0	0	138	138
MAPK11	0.007	0.002	-9999	0	0	49	49

×

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	0.032	0.19	0.53	1	-0.66	20	21
PCK1	0.048	0.12	0.52	3	-0.67	2	5
HNF4A	0.048	0.16	0.52	4	-0.71	6	10
KCNJ11	0.057	0.18	0.47	4	-0.57	17	21
AKT1	0.057	0.13	0.37	1	-0.36	17	18
response to starvation	0.003	0.002	-10000	0	-10000	0	0
DLK1	0.07	0.19	0.56	3	-0.66	9	12
NKX2-1	0.025	0.11	0.28	3	-0.33	15	18
ACADM	0.041	0.18	0.49	2	-0.72	11	13
TAT	0.045	0.13	0.5	2	-0.63	5	7
CEBPB	0.034	0.015	0.12	1	-10000	0	1
CEBPA	0.031	0.018	-10000	0	-10000	0	0
TTR	0.02	0.18	0.54	4	-0.61	15	19
PKLR	0.046	0.17	0.47	4	-0.63	9	13
APOA1	0.064	0.2	0.63	3	-0.81	8	11
CPT1C	0.045	0.16	0.44	4	-0.53	17	21
ALAS1	0.025	0.24	-10000	0	-1.2	15	15
TFRC	0.014	0.29	0.57	3	-0.97	34	37
FOXF1	0.031	0.013	-10000	0	-10000	0	0
NF1	0.034	0.036	-10000	0	-0.17	15	15
HNF1A (dimer)	0.006	0.005	0.11	1	-10000	0	1
CPT1A	0.043	0.16	0.44	3	-0.63	9	12
HMGCS1	0.047	0.17	0.56	2	-0.71	6	8
NR3C1	0.046	0.02	-10000	0	-10000	0	0
CPT1B	0.043	0.16	0.49	2	-0.68	7	9
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.036	0.005	-10000	0	-10000	0	0
GCK	0.094	0.19	0.48	17	-0.58	10	27
CREB1	0.043	0.013	0.15	1	-10000	0	1
IGFBP1	0.058	0.13	0.62	1	-0.59	6	7
PDX1	0.047	0.11	0.31	5	-0.32	10	15
UCP2	0.012	0.24	0.5	3	-0.66	48	51
ALDOB	0.057	0.18	0.48	4	-0.59	16	20
AFP	0.015	0.032	0.27	2	-10000	0	2
BDH1	0.033	0.19	0.47	2	-0.68	19	21
HADH	0.057	0.18	0.47	4	-0.57	17	21
F2	0.063	0.2	0.78	1	-0.81	8	9
HNF1A	0.006	0.005	0.11	1	-10000	0	1
G6PC	0.006	0.083	0.42	1	-10000	0	1
SLC2A2	0.055	0.13	0.44	1	-0.45	3	4
INS	0.025	0.042	0.19	14	-0.095	34	48
FOXA1	0.014	0.013	0.15	2	-10000	0	2
FOXA3	0.019	0.056	0.23	3	-0.19	21	24
FOXA2	0.091	0.22	0.65	3	-0.66	17	20
ABCC8	0.056	0.18	0.51	2	-0.63	12	14
ALB	0.016	0.032	0.3	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	0.005	-9999	0	8	8
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	39	39
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	4	-9999	4
ADCY5	-0.009	0.001	0	4	-9999	4
ADCY6	-0.017	0.006	0.085	1	-9999	1
ADCY7	-0.014	0.018	0.085	15	-9999	15
ADCY1	-0.012	0.009	-10000	0	-9999	0
ADCY2	-0.017	0.007	0.085	2	-9999	2
ADCY3	-0.009	0.001	0	4	-9999	4
ADCY8	-0.007	0.032	0.085	54	-9999	54
PRKCE	-0.011	0.001	0	4	-9999	4
ADCY9	-0.017	0.009	0.085	4	-9999	4
mol:DAG	0	0	-10000	0	-9999	0
cAMP biosynthetic process	0.018	0.043	0.17	12	-9999	12

×

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	0.006	-10000	0	0	12	12
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	0.008	-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	12	12
GRK1	0	0	-10000	0	-10000	0	0
CNG Channel	0.068	0.024	-10000	0	-10000	0	0
mol:Na +	0.043	0.016	-10000	0	-10000	0	0
mol:ADP	0	0	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.045	0.015	-10000	0	-0.12	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.054	0.018	-10000	0	-10000	0	0
CNGB1	0.035	0.007	-10000	0	0	17	17
RDH5	0.035	0.007	-10000	0	0	19	19
SAG	0.036	0.005	-10000	0	0	8	8
mol:Ca2+	-0.033	0.031	0.18	9	-10000	0	9
Na + (4 Units)	0.04	0.018	-10000	0	-10000	0	0
RGS9	0.035	0.007	-10000	0	0	17	17
GNB1/GNGT1	0.031	0.038	-10000	0	-0.14	13	13
GNAT1/GDP	0.058	0.02	-10000	0	-0.1	1	1
GUCY2D	0.036	0.006	-10000	0	0	12	12
GNGT1	0.024	0.017	-10000	0	0	172	172
GUCY2F	0.037	0	-10000	0	-10000	0	0
GNB5	0.035	0.008	-10000	0	0	24	24
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	0.006	-10000	0	0	12	12
CNGA1	0.036	0.005	-10000	0	0	11	11
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	0.009	0.029	-10000	0	-0.15	14	14
GCAP Family/Ca ++	0.023	0.001	-10000	0	-10000	0	0
PDE6A/B	0.053	0.009	-10000	0	-10000	0	0
mol:Pi	0.045	0.015	-10000	0	-0.11	1	1
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.041	0.041	-10000	0	-0.11	13	13
PDE6B	0.036	0.004	-10000	0	0	5	5
PDE6A	0.036	0.005	-10000	0	0	9	9
PDE6G	0.036	0.003	-10000	0	0	3	3
RHO	0.036	0.006	-10000	0	0	14	14
PDE6	0.084	0.027	-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	6	6
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