PARADIGM pathway analysis of mRNASeq expression data - Cholangiocarcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
FOXA2 and FOXA3 transcription factor networks	18
HIF-1-alpha transcription factor network	12
Plasma membrane estrogen receptor signaling	12
Class IB PI3K non-lipid kinase events	12
Syndecan-4-mediated signaling events	11
Signaling events regulated by Ret tyrosine kinase	10
IGF1 pathway	9
Reelin signaling pathway	8
Nongenotropic Androgen signaling	8
EPO signaling pathway	7

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
FOXA2 and FOXA3 transcription factor networks	0.5000	18	837	46	-1.9	0.061	1000	-1000	-0.067	-1000
HIF-1-alpha transcription factor network	0.3333	12	925	76	-1.3	0.018	1000	-1000	-0.16	-1000
Plasma membrane estrogen receptor signaling	0.3333	12	1040	86	-0.91	0.73	1000	-1000	-0.11	-1000
Class IB PI3K non-lipid kinase events	0.3333	12	36	3	-0.44	-1000	1000	-1000	-0.036	-1000
Syndecan-4-mediated signaling events	0.3056	11	796	67	-1	0.13	1000	-1000	-0.12	-1000
Signaling events regulated by Ret tyrosine kinase	0.2778	10	865	82	-0.8	0	1000	-1000	-0.13	-1000
IGF1 pathway	0.2500	9	513	57	-0.69	0.28	1000	-1000	-0.13	-1000
Reelin signaling pathway	0.2222	8	480	56	-0.71	0.039	1000	-1000	-0.13	-1000
Nongenotropic Androgen signaling	0.2222	8	447	52	-1	0.17	1000	-1000	-0.085	-1000
EPO signaling pathway	0.1944	7	425	55	-0.42	0	1000	-1000	-0.13	-1000
amb2 Integrin signaling	0.1667	6	563	82	-1	0.06	1000	-1000	-0.1	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1111	4	261	54	-0.74	0.022	1000	-1000	-0.12	-1000
Syndecan-2-mediated signaling events	0.1111	4	283	69	-1	0	1000	-1000	-0.088	-1000
p75(NTR)-mediated signaling	0.1111	4	534	125	-0.65	0	1000	-1000	-0.15	-1000
Glypican 1 network	0.1111	4	204	48	-1.1	0.011	1000	-1000	-0.074	-1000
Arf6 signaling events	0.0833	3	218	62	-0.62	0.021	1000	-1000	-0.087	-1000
S1P5 pathway	0.0833	3	63	17	-0.54	0.17	1000	-1000	-0.062	-1000
Integrins in angiogenesis	0.0833	3	262	84	-0.91	0.012	1000	-1000	-0.13	-1000
IL27-mediated signaling events	0.0833	3	197	51	-0.87	0.39	1000	-1000	-0.12	-1000
IL6-mediated signaling events	0.0833	3	298	75	-0.67	0.054	1000	-1000	-0.12	-1000
S1P4 pathway	0.0833	3	81	25	-0.54	0	1000	-1000	-0.076	-1000
Coregulation of Androgen receptor activity	0.0556	2	192	76	-0.6	0.022	1000	-1000	-0.079	-1000
Signaling events mediated by the Hedgehog family	0.0556	2	155	52	-0.46	0.3	1000	-1000	-0.099	-1000
Thromboxane A2 receptor signaling	0.0556	2	223	105	-0.073	0.056	1000	-1000	-0.11	-1000
IL4-mediated signaling events	0.0556	2	252	91	-1.2	0.4	1000	-1000	-0.14	-1000
BMP receptor signaling	0.0556	2	220	81	-1.1	0.043	1000	-1000	-0.1	-1000
S1P1 pathway	0.0556	2	76	36	-0.54	0.004	1000	-1000	-0.087	-1000
Wnt signaling	0.0556	2	17	7	-0.29	0	1000	-1000	-0.055	-1000
S1P3 pathway	0.0556	2	109	42	-0.54	0.013	1000	-1000	-0.066	-1000
Visual signal transduction: Rods	0.0556	2	135	52	-0.62	0	1000	-1000	-0.1	-1000
Signaling events mediated by PRL	0.0556	2	73	34	-0.87	0.022	1000	-1000	-0.089	-1000
ErbB2/ErbB3 signaling events	0.0278	1	120	65	-0.25	0.03	1000	-1000	-0.093	-1000
IL12-mediated signaling events	0.0278	1	122	87	-0.61	0.03	1000	-1000	-0.14	-1000
ErbB4 signaling events	0.0278	1	124	69	-0.21	0.042	1000	-1000	-0.12	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0278	1	34	28	-0.54	0.002	1000	-1000	-0.074	-1000
Noncanonical Wnt signaling pathway	0.0278	1	35	26	-0.29	0	1000	-1000	-0.097	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0278	1	94	85	-0.22	0.011	1000	-1000	-0.1	-1000
Glucocorticoid receptor regulatory network	0.0278	1	227	114	-0.95	0.086	1000	-1000	-0.099	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0278	1	51	37	-0.44	0	1000	-1000	-0.11	-1000
Signaling events mediated by HDAC Class III	0.0278	1	64	40	-1.1	0.011	1000	-1000	-0.079	-1000
HIF-2-alpha transcription factor network	0.0278	1	43	43	-0.34	0.14	1000	-1000	-0.11	-1000
FoxO family signaling	0.0278	1	85	64	-1.1	0.071	1000	-1000	-0.094	-1000
Calcium signaling in the CD4+ TCR pathway	0.0278	1	31	31	-0.12	0.026	1000	-1000	-0.15	-1000
LPA receptor mediated events	0.0278	1	142	102	-0.45	0.026	1000	-1000	-0.14	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0278	1	114	88	-1	0.24	1000	-1000	-0.11	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0278	1	179	120	-0.5	0.093	1000	-1000	-0.12	-1000
FOXM1 transcription factor network	0.0278	1	65	51	-0.94	0.009	1000	-1000	-0.17	-1000
p38 MAPK signaling pathway	0.0278	1	85	44	-0.62	0	1000	-1000	-0.079	-1000
LPA4-mediated signaling events	0.0000	0	3	12	-0.064	0.021	1000	-1000	-0.048	-1000
Caspase cascade in apoptosis	0.0000	0	35	74	-0.14	0.049	1000	-1000	-0.084	-1000
Regulation of nuclear SMAD2/3 signaling	0.0000	0	108	136	-0.91	0.17	1000	-1000	-0.098	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	0	23	0	0.042	1000	-1000	-0.088	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0000	0	0	34	-0.002	0.002	1000	-1000	-0.11	-1000
Canonical NF-kappaB pathway	0.0000	0	0	39	-0.005	0.084	1000	-1000	-0.11	-1000
Signaling events mediated by HDAC Class II	0.0000	0	50	75	-0.91	0	1000	-1000	-0.093	-1000
BARD1 signaling events	0.0000	0	0	57	-0.043	0.054	1000	-1000	-0.12	-1000
Syndecan-1-mediated signaling events	0.0000	0	29	34	-0.22	0.015	1000	-1000	-0.093	-1000
PLK2 and PLK4 events	0.0000	0	0	3	-0.005	0.019	1000	-1000	-0.03	-1000
Visual signal transduction: Cones	0.0000	0	0	38	-0.011	0.006	1000	-1000	-0.087	-1000
Circadian rhythm pathway	0.0000	0	0	22	-0.014	0.05	1000	-1000	-0.091	-1000
Osteopontin-mediated events	0.0000	0	11	38	-0.13	0.051	1000	-1000	-0.14	-1000
Ephrin A reverse signaling	0.0000	0	0	7	-0.043	0	1000	-1000	-0.049	-1000
JNK signaling in the CD4+ TCR pathway	0.0000	0	5	17	-0.042	0.051	1000	-1000	-0.1	-1000
a4b1 and a4b7 Integrin signaling	0.0000	0	2	5	-0.036	0	1000	-1000	-0.049	-1000
Cellular roles of Anthrax toxin	0.0000	0	4	39	-0.03	0.021	1000	-1000	-0.037	-1000
Signaling events mediated by PTP1B	0.0000	0	55	76	-0.43	0.053	1000	-1000	-0.11	-1000
Hedgehog signaling events mediated by Gli proteins	0.0000	0	39	65	-0.54	0.047	1000	-1000	-0.095	-1000
Presenilin action in Notch and Wnt signaling	0.0000	0	20	61	-0.11	0.044	1000	-1000	-0.087	-1000
Aurora A signaling	0.0000	0	0	60	-0.1	0.033	1000	-1000	-0.079	-1000
Arf6 downstream pathway	0.0000	0	3	43	-0.036	0.028	1000	-1000	-0.064	-1000
Aurora C signaling	0.0000	0	2	7	-0.054	0	1000	-1000	-0.059	-1000
Fc-epsilon receptor I signaling in mast cells	0.0000	0	54	97	-0.11	0.053	1000	-1000	-0.14	-1000
PLK1 signaling events	0.0000	0	1	85	-0.1	0.032	1000	-1000	-0.081	-1000
Insulin-mediated glucose transport	0.0000	0	4	32	-0.17	0.022	1000	-1000	-0.079	-1000
PDGFR-alpha signaling pathway	0.0000	0	9	44	-0.13	0.027	1000	-1000	-0.089	-1000
mTOR signaling pathway	0.0000	0	0	53	-0.005	0.034	1000	-1000	-0.073	-1000
IFN-gamma pathway	0.0000	0	17	68	-0.62	0.083	1000	-1000	-0.12	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	4	68	-0.17	0.044	1000	-1000	-0.096	-1000
Nectin adhesion pathway	0.0000	0	27	63	-0.048	0.041	1000	-1000	-0.096	-1000
Ceramide signaling pathway	0.0000	0	58	76	-0.69	0.035	1000	-1000	-0.089	-1000
TRAIL signaling pathway	0.0000	0	1	48	-0.005	0.029	1000	-1000	-0.11	-1000
IL1-mediated signaling events	0.0000	0	46	62	-0.4	0.023	1000	-1000	-0.15	-1000
ceramide signaling pathway	0.0000	0	1	49	-0.005	0.06	1000	-1000	-0.071	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0000	0	26	52	-0.11	0.06	1000	-1000	-0.1	-1000
Ephrin B reverse signaling	0.0000	0	19	48	-0.064	0.026	1000	-1000	-0.09	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0000	0	5	83	-0.17	0.057	1000	-1000	-0.096	-1000
Endothelins	0.0000	0	95	96	-0.54	0.07	1000	-1000	-0.11	-1000
Signaling events mediated by HDAC Class I	0.0000	0	1	104	-0.014	0.046	1000	-1000	-0.091	-1000
TCGA08_p53	0.0000	0	0	7	-0.015	0.014	1000	-1000	-0.037	-1000
FAS signaling pathway (CD95)	0.0000	0	17	47	-0.22	0.046	1000	-1000	-0.069	-1000
Signaling mediated by p38-gamma and p38-delta	0.0000	0	0	15	-0.006	0.025	1000	-1000	-0.075	-1000
Retinoic acid receptors-mediated signaling	0.0000	0	8	58	-0.073	0.052	1000	-1000	-0.11	-1000
Paxillin-dependent events mediated by a4b1	0.0000	0	7	36	-0.073	0.022	1000	-1000	-0.099	-1000
Atypical NF-kappaB pathway	0.0000	0	3	31	-0.036	0.028	1000	-1000	-0.094	-1000
Syndecan-3-mediated signaling events	0.0000	0	10	35	-0.073	0	1000	-1000	-0.086	-1000
IL2 signaling events mediated by PI3K	0.0000	0	0	58	-0.016	0.093	1000	-1000	-0.098	-1000
Signaling mediated by p38-alpha and p38-beta	0.0000	0	31	44	-0.4	0.04	1000	-1000	-0.076	-1000
TCR signaling in naïve CD8+ T cells	0.0000	0	11	93	-0.043	0.068	1000	-1000	-0.099	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0000	0	5	45	-0.036	0.077	1000	-1000	-0.12	-1000
Canonical Wnt signaling pathway	0.0000	0	1	51	-0.075	0.062	1000	-1000	-0.084	-1000
EPHB forward signaling	0.0000	0	59	85	-0.72	0.04	1000	-1000	-0.12	-1000
Regulation of p38-alpha and p38-beta	0.0000	0	2	54	-0.036	0.074	1000	-1000	-0.096	-1000
Effects of Botulinum toxin	0.0000	0	0	26	-0.011	0.003	1000	-1000	-0.077	-1000
Glypican 2 network	0.0000	0	0	4	-0.037	-0.016	1000	-1000	-0.043	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0000	0	74	125	-0.038	0.07	1000	-1000	-0.15	-1000
TCGA08_rtk_signaling	0.0000	0	4	26	-0.073	0.046	1000	-1000	-0.043	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0000	0	64	68	-0.12	0.087	1000	-1000	-0.16	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0000	0	54	74	-0.69	0.086	1000	-1000	-0.14	-1000
E-cadherin signaling in the nascent adherens junction	0.0000	0	7	76	-0.036	0.063	1000	-1000	-0.11	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0	1000	-1000	-0.088	-1000
IL2 signaling events mediated by STAT5	0.0000	0	0	22	-0.027	0.074	1000	-1000	-0.083	-1000
Class I PI3K signaling events	0.0000	0	4	73	-0.046	0.066	1000	-1000	-0.11	-1000
Arf6 trafficking events	0.0000	0	21	71	-0.37	0.038	1000	-1000	-0.11	-1000
TCGA08_retinoblastoma	0.0000	0	0	8	-0.037	0.008	1000	-1000	-0.038	-1000
Regulation of Telomerase	0.0000	0	85	102	-0.91	0.034	1000	-1000	-0.15	-1000
BCR signaling pathway	0.0000	0	53	99	-0.085	0.041	1000	-1000	-0.15	-1000
EGFR-dependent Endothelin signaling events	0.0000	0	18	21	-0.073	0	1000	-1000	-0.11	-1000
IL23-mediated signaling events	0.0000	0	7	60	-0.045	0.13	1000	-1000	-0.15	-1000
Insulin Pathway	0.0000	0	19	74	-0.11	0.035	1000	-1000	-0.13	-1000
VEGFR1 specific signals	0.0000	0	1	56	0	0.065	1000	-1000	-0.12	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0000	0	0	33	-0.043	0.003	1000	-1000	-0.093	-1000
Rapid glucocorticoid signaling	0.0000	0	1	20	-0.017	0.001	1000	-1000	-0.064	-1000
PDGFR-beta signaling pathway	0.0000	0	3	97	-0.036	0.069	1000	-1000	-0.13	-1000
E-cadherin signaling in keratinocytes	0.0000	0	18	43	-0.073	0.044	1000	-1000	-0.099	-1000
E-cadherin signaling events	0.0000	0	0	5	0	0	1000	-1000	-0.064	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0000	0	26	78	-0.43	0.049	1000	-1000	-0.093	-1000
Arf1 pathway	0.0000	0	3	54	-0.036	0.025	1000	-1000	-0.07	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0	1000	-1000	-0.079	-1000
Regulation of Androgen receptor activity	0.0000	0	47	70	-0.22	0.025	1000	-1000	-0.11	-1000
Ras signaling in the CD4+ TCR pathway	0.0000	0	7	17	-0.042	0.02	1000	-1000	-0.072	-1000
Aurora B signaling	0.0000	0	3	67	-0.16	0.02	1000	-1000	-0.089	-1000
Total	NA	184	13802	7203	-47	-990	131000	-131000	-13	-131000

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-1.5	0.64	-9999	-1.8	29	29
PCK1	-1.7	0.77	-9999	-2.1	29	29
HNF4A	-1.8	0.76	-9999	-2.1	29	29
KCNJ11	-1.5	0.65	-9999	-1.8	29	29
AKT1	-0.39	0.14	-9999	-10000	0	0
response to starvation	-0.004	0.005	-9999	-10000	0	0
DLK1	-1.5	0.65	-9999	-1.8	29	29
NKX2-1	-0.28	0.12	-9999	-10000	0	0
ACADM	-1.5	0.64	-9999	-1.8	29	29
TAT	-1.8	0.69	-9999	-2.1	30	30
CEBPB	-0.015	0.022	-9999	-10000	0	0
CEBPA	-0.23	0.49	-9999	-1.3	6	6
TTR	-1.5	0.42	-9999	-1.7	33	33
PKLR	-1.7	0.68	-9999	-2	31	31
APOA1	-1.8	0.76	-9999	-2.2	29	29
CPT1C	-1.5	0.64	-9999	-1.8	29	29
ALAS1	-0.41	0.15	-9999	-10000	0	0
TFRC	-1.2	0.59	-9999	-1.4	29	29
FOXF1	0	0	-9999	-10000	0	0
NF1	0.016	0.001	-9999	-10000	0	0
HNF1A (dimer)	-0.072	0.23	-9999	-1.4	1	1
CPT1A	-1.5	0.64	-9999	-1.8	29	29
HMGCS1	-1.5	0.64	-9999	-1.8	29	29
NR3C1	-0.084	0.07	-9999	-10000	0	0
CPT1B	-1.5	0.64	-9999	-1.8	29	29
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.014	0.005	-9999	-10000	0	0
GCK	-1.8	0.56	-9999	-1.9	33	33
CREB1	-0.031	0.042	-9999	-10000	0	0
IGFBP1	-1.3	0.84	-9999	-2	22	22
PDX1	-0.5	0.36	-9999	-2.4	1	1
UCP2	-1.5	0.64	-9999	-1.8	29	29
ALDOB	-1.9	0.74	-9999	-2.2	30	30
AFP	-0.97	0.76	-9999	-1.6	19	19
BDH1	-1.7	0.72	-9999	-2	29	29
HADH	-1.5	0.65	-9999	-1.8	29	29
F2	-1.8	0.76	-9999	-2.2	29	29
HNF1A	-0.072	0.23	-9999	-1.4	1	1
G6PC	-1.3	0.77	-9999	-1.8	25	25
SLC2A2	-1.7	0.83	-9999	-2.2	28	28
INS	0.061	0.061	-9999	-10000	0	0
FOXA1	-0.25	0.32	-9999	-0.91	4	4
FOXA3	-0.71	0.55	-9999	-0.99	21	21
FOXA2	-1.9	0.87	-9999	-2.3	29	29
ABCC8	-1.5	0.65	-9999	-1.8	29	29
ALB	-1.6	0.7	-9999	-1.9	30	30

×

HIF-1-alpha 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.85	0.55	-9999	-1.3	19	19
HDAC7	0	0	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.75	0.43	-9999	-1.1	18	18
SMAD4	0	0	-9999	-10000	0	0
ID2	-0.82	0.54	-9999	-1.3	17	17
AP1	-0.09	0.3	-9999	-1.1	3	3
ABCG2	-1	0.68	-9999	-1.6	18	18
HIF1A	-0.073	0.044	-9999	-10000	0	0
TFF3	-0.83	0.55	-9999	-1.3	17	17
GATA2	-0.005	0.032	-9999	-10000	0	0
AKT1	-0.14	0.089	-9999	-10000	0	0
response to hypoxia	-0.16	0.096	-9999	-10000	0	0
MCL1	-0.82	0.54	-9999	-1.3	17	17
NDRG1	-0.82	0.54	-9999	-1.3	19	19
SERPINE1	-0.86	0.59	-9999	-1.4	17	17
FECH	-0.82	0.54	-9999	-1.3	17	17
FURIN	-0.82	0.54	-9999	-1.3	16	16
NCOA2	-0.071	0.3	-9999	-1.3	2	2
EP300	-0.23	0.16	-9999	-0.38	14	14
HMOX1	-0.82	0.54	-9999	-1.3	17	17
BHLHE40	-0.82	0.54	-9999	-1.3	17	17
BHLHE41	-0.82	0.54	-9999	-1.3	17	17
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.057	0.04	-9999	-10000	0	0
ENG	-0.046	0.035	-9999	-10000	0	0
JUN	0	0	-9999	-10000	0	0
RORA	-0.82	0.54	-9999	-1.3	17	17
ABCB1	-0.45	0.68	-9999	-1.8	7	7
TFRC	-0.82	0.54	-9999	-1.3	16	16
CXCR4	-0.82	0.54	-9999	-1.3	17	17
TF	-1.3	0.56	-9999	-1.6	28	28
CITED2	-0.82	0.54	-9999	-1.3	17	17
HIF1A/ARNT	-1	0.72	-9999	-1.6	19	19
LDHA	-0.095	0.047	-9999	-10000	0	0
ETS1	-0.82	0.54	-9999	-1.3	16	16
PGK1	-0.82	0.54	-9999	-1.3	17	17
NOS2	-0.83	0.54	-9999	-1.3	16	16
ITGB2	-0.82	0.54	-9999	-1.3	17	17
ALDOA	-0.82	0.54	-9999	-1.3	16	16
Cbp/p300/CITED2	-0.97	0.59	-9999	-1.4	23	23
FOS	-0.11	0.36	-9999	-1.3	3	3
HK2	-0.83	0.54	-9999	-1.3	17	17
SP1	0.016	0.008	-9999	-10000	0	0
GCK	-1.1	0.86	-9999	-1.8	21	21
HK1	-0.82	0.54	-9999	-1.3	17	17
NPM1	-0.82	0.54	-9999	-1.3	16	16
EGLN1	-0.82	0.54	-9999	-1.3	19	19
CREB1	0.018	0	-9999	-10000	0	0
PGM1	-0.83	0.55	-9999	-1.3	17	17
SMAD3	0	0	-9999	-10000	0	0
EDN1	-0.3	0.24	-9999	-0.78	2	2
IGFBP1	-1.1	0.71	-9999	-1.6	23	23
VEGFA	-0.6	0.34	-9999	-0.96	11	11
HIF1A/JAB1	-0.038	0.025	-9999	-10000	0	0
CP	-1.1	0.7	-9999	-1.6	23	23
CXCL12	-0.88	0.55	-9999	-1.3	19	19
COPS5	0	0	-9999	-10000	0	0
SMAD3/SMAD4	0	0	-9999	-10000	0	0
BNIP3	-0.82	0.54	-9999	-1.3	16	16
EGLN3	-0.84	0.55	-9999	-1.3	17	17
CA9	-0.86	0.58	-9999	-1.4	17	17
TERT	-0.82	0.55	-9999	-1.4	16	16
ENO1	-0.82	0.54	-9999	-1.3	17	17
PFKL	-0.82	0.54	-9999	-1.3	17	17
NCOA1	0	0	-9999	-10000	0	0
ADM	-0.82	0.54	-9999	-1.3	17	17
ARNT	-0.071	0.041	-9999	-10000	0	0
HNF4A	-0.069	0.21	-9999	-1.3	1	1
ADFP	-0.82	0.55	-9999	-1.3	19	19
SLC2A1	-0.61	0.35	-9999	-0.96	13	13
LEP	-0.82	0.55	-9999	-1.3	17	17
HIF1A/ARNT/Cbp/p300	-0.77	0.44	-9999	-1.1	18	18
EPO	-0.71	0.57	-9999	-1.4	13	13
CREBBP	-0.23	0.16	-9999	-0.38	17	17
HIF1A/ARNT/Cbp/p300/HDAC7	-0.74	0.43	-9999	-1.1	17	17
PFKFB3	-0.82	0.54	-9999	-1.3	17	17
NT5E	-0.82	0.54	-9999	-1.3	17	17

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.62	0.4	-10000	0	-0.88	25	25
ER alpha/Gai/GDP/Gbeta gamma	-0.76	0.61	-10000	0	-1.1	25	25
AKT1	-0.81	0.54	-10000	0	-1.2	25	25
PIK3CA	0	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.83	0.56	-10000	0	-1.2	25	25
mol:Ca2+	-0.17	0.24	-10000	0	-1.1	2	2
IGF1R	-0.005	0.032	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.69	0.46	-10000	0	-0.99	25	25
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	0.73	0.51	1.1	25	-10000	0	25
RhoA/GTP	-0.54	0.36	-10000	0	-0.78	25	25
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.68	0.47	-10000	0	-0.98	25	25
regulation of stress fiber formation	0.37	0.29	0.56	25	-10000	0	25
E2/ERA-ERB (dimer)	-0.69	0.45	-10000	0	-0.99	25	25
KRAS	0	0	-10000	0	-10000	0	0
G13/GTP	-0.64	0.43	-10000	0	-0.93	25	25
pseudopodium formation	-0.37	0.29	-10000	0	-0.56	25	25
E2/ER alpha (dimer)/PELP1	-0.69	0.46	-10000	0	-0.99	25	25
GRB2	0	0	-10000	0	-10000	0	0
GNG2	0	0	-10000	0	-10000	0	0
GNAO1	-0.54	0.64	-10000	0	-1.3	15	15
HRAS	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.62	0.47	-10000	0	-0.91	25	25
E2/ER beta (dimer)	-0.007	0.029	-10000	0	-10000	0	0
mol:GDP	-0.64	0.43	-10000	0	-0.93	25	25
mol:NADP	-0.62	0.47	-10000	0	-0.91	25	25
PIK3R1	0	0	-10000	0	-10000	0	0
mol:IP3	-0.18	0.27	-10000	0	-1.2	2	2
IGF-1R heterotetramer	-0.005	0.032	-10000	0	-10000	0	0
PLCB1	-0.21	0.27	-10000	0	-1.2	2	2
PLCB2	-0.2	0.27	-10000	0	-1.2	2	2
IGF1	-0.69	0.65	-10000	0	-1.3	19	19
mol:L-citrulline	-0.62	0.47	-10000	0	-0.91	25	25
RHOA	0	0	-10000	0	-10000	0	0
Gai/GDP	-0.55	0.62	-10000	0	-1.3	15	15
JNK cascade	-0.007	0.029	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	-0.011	0.044	-10000	0	-10000	0	0
GNAQ	0	0	-10000	0	-10000	0	0
ESR1	-0.91	0.6	-10000	0	-1.3	25	25
Gq family/GDP/Gbeta gamma	-0.037	0.11	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.3	0.23	-10000	0	-0.45	25	25
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.68	0.47	-10000	0	-0.98	25	25
GNAZ	-0.032	0.072	-10000	0	-10000	0	0
E2/ER alpha (dimer)	-0.76	0.5	-10000	0	-1.1	25	25
STRN	0	0	-10000	0	-10000	0	0
GNAL	-0.005	0.032	-10000	0	-10000	0	0
PELP1	0	0	-10000	0	-10000	0	0
MAPK11	-0.005	0.021	-10000	0	-10000	0	0
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	0	0	-10000	0	-10000	0	0
HBEGF	-0.56	0.46	-10000	0	-0.94	19	19
cAMP biosynthetic process	-0.58	0.38	-10000	0	-0.83	25	25
SRC	-0.66	0.56	-10000	0	-0.97	25	25
PI3K	0	0	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.56	0.37	-10000	0	-0.8	25	25
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.59	0.38	-10000	0	-0.82	26	26
Gs family/GTP	-0.6	0.39	-10000	0	-0.86	25	25
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0	0	-10000	0	-10000	0	0
vasodilation	-0.56	0.43	-10000	0	-0.84	25	25
mol:DAG	-0.18	0.27	-10000	0	-1.2	2	2
Gs family/GDP/Gbeta gamma	-0.49	0.32	-10000	0	-0.7	25	25
MSN	-0.41	0.32	-10000	0	-0.62	25	25
Gq family/GTP	-0.22	0.3	-10000	0	-1.4	2	2
mol:PI-3-4-5-P3	-0.76	0.53	-10000	0	-1.1	25	25
NRAS	0	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.56	0.43	0.84	25	-10000	0	25
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.59	0.39	-10000	0	-0.84	25	25
NOS3	-0.69	0.53	-10000	0	-1	25	25
GNA11	0	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.63	0.46	-10000	0	-0.93	25	25
E2/ER alpha (dimer)/PELP1/Src	-0.75	0.51	-10000	0	-1.1	25	25
ruffle organization	-0.37	0.29	-10000	0	-0.56	25	25
ROCK2	-0.5	0.34	-10000	0	-0.72	25	25
GNA14	-0.073	0.3	-10000	0	-1.3	2	2
GNA15	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
MMP9	-0.59	0.48	-10000	0	-1	17	17
MMP2	-0.58	0.48	-10000	0	-1.1	15	15

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.43	0.61	1.3	12	-10000	0	12
PI3K Class IB/PDE3B	-0.43	0.61	-10000	0	-1.3	12	12
PDE3B	-0.44	0.62	-10000	0	-1.3	12	12

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.079	0.16	-9999	-0.99	1	1
Syndecan-4/Syndesmos	-0.87	0.46	-9999	-1.1	28	28
positive regulation of JNK cascade	-0.77	0.37	-9999	-0.94	29	29
Syndecan-4/ADAM12	-0.87	0.46	-9999	-1.1	28	28
CCL5	-0.036	0.22	-9999	-1.3	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0	0	-9999	-10000	0	0
ITGA5	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
PLG	-0.64	0.64	-9999	-1.3	18	18
ADAM12	-0.011	0.044	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.13	0.069	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.87	0.46	-9999	-1.1	28	28
Syndecan-4/CXCL12/CXCR4	-0.87	0.42	-9999	-1.1	29	29
Syndecan-4/Laminin alpha3	-0.88	0.46	-9999	-1.1	28	28
MDK	-0.037	0.076	-9999	-10000	0	0
Syndecan-4/FZD7	-0.87	0.46	-9999	-1.1	28	28
Syndecan-4/Midkine	-0.88	0.46	-9999	-1.1	28	28
FZD7	0	0	-9999	-10000	0	0
Syndecan-4/FGFR1/FGF	-0.78	0.41	-9999	-0.99	28	28
THBS1	-0.036	0.22	-9999	-1.3	1	1
integrin-mediated signaling pathway	-0.8	0.42	-9999	-1	28	28
positive regulation of MAPKKK cascade	-0.77	0.37	-9999	-0.94	29	29
Syndecan-4/TACI	-0.87	0.46	-9999	-1.1	28	28
CXCR4	-0.005	0.032	-9999	-10000	0	0
cell adhesion	-0.015	0.095	-9999	-0.58	1	1
Syndecan-4/Dynamin	-0.87	0.46	-9999	-1.1	28	28
Syndecan-4/TSP1	-0.89	0.47	-9999	-1.1	28	28
Syndecan-4/GIPC	-0.87	0.46	-9999	-1.1	28	28
Syndecan-4/RANTES	-0.89	0.47	-9999	-1.1	28	28
ITGB1	0	0	-9999	-10000	0	0
LAMA1	-0.021	0.061	-9999	-10000	0	0
LAMA3	-0.016	0.053	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.13	0.066	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	-0.87	0.46	-9999	-1.1	28	28
TFPI	-0.29	0.54	-9999	-1.3	8	8
F2	-1	0.54	-9999	-1.3	28	28
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.82	0.45	-9999	-1.1	28	28
ACTN1	0	0	-9999	-10000	0	0
TNC	-0.021	0.061	-9999	-10000	0	0
Syndecan-4/CXCL12	-0.92	0.46	-9999	-1.1	29	29
FGF6	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CXCL12	-0.11	0.36	-9999	-1.3	3	3
TNFRSF13B	-0.005	0.032	-9999	-10000	0	0
FGF2	-0.036	0.22	-9999	-1.3	1	1
FGFR1	-0.005	0.032	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.87	0.48	-9999	-1.1	28	28
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.01	0.22	-9999	-1.3	1	1
cell migration	-0.037	0.02	-9999	-10000	0	0
PRKCD	0.026	0.014	-9999	-10000	0	0
vasculogenesis	-0.81	0.42	-9999	-1	28	28
SDC4	-0.97	0.54	-9999	-1.2	28	28
Syndecan-4/Tenascin C	-0.87	0.46	-9999	-1.1	28	28
Syndecan-4/PI-4-5-P2/PKC alpha	-0.1	0.053	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.87	0.46	-9999	-1.1	28	28
MMP9	-0.02	0.058	-9999	-10000	0	0
Rac1/GTP	-0.017	0.099	-9999	-0.6	1	1
cytoskeleton organization	-0.8	0.42	-9999	-1	28	28
GIPC1	0	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.98	0.53	-9999	-1.2	28	28

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.12	0.094	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.32	0.26	-9999	-0.63	4	4
JUN	-0.3	0.32	-9999	-0.89	5	5
HRAS	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.65	0.57	-9999	-1.1	22	22
RAP1A	0	0	-9999	-10000	0	0
FRS2	0	0	-9999	-10000	0	0
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.65	0.57	-9999	-1.1	22	22
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.57	0.45	-9999	-0.93	22	22
RHOA	0	0	-9999	-10000	0	0
RAP1A/GTP	-0.58	0.5	-9999	-0.96	22	22
GRB7	-0.036	0.22	-9999	-1.3	1	1
RET51/GFRalpha1/GDNF	-0.65	0.57	-9999	-1.1	22	22
MAPKKK cascade	-0.48	0.4	-9999	-0.79	22	22
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.57	0.45	-9999	-0.93	22	22
lamellipodium assembly	-0.29	0.23	-9999	-0.47	22	22
RET51/GFRalpha1/GDNF/SHC	-0.65	0.57	-9999	-1.1	22	22
PIK3CA	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.57	0.45	-9999	-0.93	22	22
RET9/GFRalpha1/GDNF/Shank3	-0.57	0.45	-9999	-0.93	22	22
MAPK3	-0.54	0.46	-9999	-0.88	22	22
DOK1	0	0	-9999	-10000	0	0
DOK6	0	0	-9999	-10000	0	0
PXN	0	0	-9999	-10000	0	0
neurite development	-0.48	0.41	-9999	-0.79	22	22
DOK5	0	0	-9999	-10000	0	0
GFRA1	-0.8	0.64	-9999	-1.3	22	22
MAPK8	-0.34	0.33	-9999	-0.96	5	5
HRAS/GTP	-0.58	0.5	-9999	-0.95	22	22
tube development	-0.54	0.43	-9999	-0.88	22	22
MAPK1	-0.54	0.46	-9999	-0.88	22	22
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.29	0.23	-9999	-0.48	22	22
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
PDLIM7	-0.005	0.032	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.62	0.55	-9999	-1	22	22
SHC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.65	0.57	-9999	-1.1	22	22
RET51/GFRalpha1/GDNF/Dok5	-0.65	0.57	-9999	-1.1	22	22
PRKCA	0	0	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.34	0.29	-9999	-0.56	22	22
PIK3R1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.29	0.23	-9999	-0.48	22	22
RET51/GFRalpha1/GDNF/Grb7	-0.68	0.56	-9999	-1.1	23	23
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.14	0.41	-9999	-1.3	4	4
DOK4	0	0	-9999	-10000	0	0
JNK cascade	-0.29	0.31	-9999	-0.86	5	5
RET9/GFRalpha1/GDNF/FRS2	-0.57	0.45	-9999	-0.93	22	22
SHANK3	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.29	0.23	-9999	-0.48	22	22
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.34	0.3	-9999	-0.55	22	22
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.34	0.3	-9999	-0.55	22	22
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.4	0.45	-9999	-0.66	22	22
PI3K	-0.51	0.42	-9999	-0.84	22	22
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.54	0.43	-9999	-0.88	22	22
GRB10	0	0	-9999	-10000	0	0
activation of MAPKK activity	-0.31	0.27	-9999	-0.79	4	4
RET51/GFRalpha1/GDNF/FRS2	-0.65	0.57	-9999	-1.1	22	22
GAB1	0	0	-9999	-10000	0	0
IRS1	0	0	-9999	-10000	0	0
IRS2	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.4	0.45	-9999	-0.66	22	22
RET51/GFRalpha1/GDNF/PKC alpha	-0.65	0.57	-9999	-1.1	22	22
GRB2	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GDNF	-0.005	0.032	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.65	0.57	-9999	-1.1	22	22
Rac1/GTP	-0.36	0.29	-9999	-0.59	22	22
RET9/GFRalpha1/GDNF	-0.61	0.48	-9999	-0.99	22	22
GFRalpha1/GDNF	-0.67	0.53	-9999	-1.1	22	22

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0	0	-9999	-10000	0	0
PTK2	0	0	-9999	-10000	0	0
CRKL	-0.44	0.41	-9999	-0.82	19	19
GRB2/SOS1/SHC	0	0	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
IRS1/Crk	-0.44	0.41	-9999	-0.83	19	19
IGF-1R heterotetramer/IGF1/PTP1B	-0.5	0.47	-9999	-0.94	19	19
AKT1	-0.34	0.37	-9999	-0.69	19	19
BAD	-0.31	0.34	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.44	0.41	-9999	-0.82	19	19
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.44	0.42	-9999	-0.83	19	19
RAF1	-0.29	0.32	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.42	0.4	-9999	-0.8	19	19
YWHAZ	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.47	0.44	-9999	-0.89	19	19
PIK3CA	0	0	-9999	-10000	0	0
RPS6KB1	-0.34	0.37	-9999	-0.69	19	19
GNB2L1	0	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	-0.24	0.27	-9999	-10000	0	0
PXN	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.38	0.36	-9999	-0.71	19	19
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.42	0.4	-9999	-0.8	19	19
IGF-1R heterotetramer	-0.071	0.065	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.44	0.42	-9999	-0.83	19	19
Crk/p130 Cas/Paxillin	-0.4	0.38	-9999	-0.76	19	19
IGF1R	-0.072	0.065	-9999	-10000	0	0
IGF1	-0.69	0.66	-9999	-1.3	19	19
IRS2/Crk	-0.42	0.39	-9999	-0.79	19	19
PI3K	-0.41	0.4	-9999	-0.79	19	19
apoptosis	0.28	0.26	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
PRKCD	-0.43	0.44	-9999	-0.85	19	19
RAF1/14-3-3 E	-0.26	0.24	-9999	-10000	0	0
BAD/14-3-3	-0.3	0.28	-9999	-10000	0	0
PRKCZ	-0.34	0.37	-9999	-0.69	19	19
Crk/p130 Cas/Paxillin/FAK1	-0.3	0.29	-9999	-10000	0	0
PTPN1	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.48	0.45	-9999	-0.9	19	19
BCAR1	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.45	0.43	-9999	-0.86	19	19
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
IRS1/NCK2	-0.43	0.41	-9999	-0.82	19	19
GRB10	0	0	-9999	-10000	0	0
PTPN11	-0.44	0.41	-9999	-0.82	19	19
IRS1	-0.46	0.44	-9999	-0.88	19	19
IRS2	-0.44	0.41	-9999	-0.82	19	19
IGF-1R heterotetramer/IGF1	-0.58	0.55	-9999	-1.1	19	19
GRB2	0	0	-9999	-10000	0	0
PDPK1	-0.39	0.37	-9999	-0.74	19	19
YWHAE	0	0	-9999	-10000	0	0
PRKD1	-0.43	0.44	-9999	-0.85	19	19
SHC1	0	0	-9999	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.003	0.019	-9999	-10000	0	0
VLDLR	-0.005	0.032	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
LRPAP1	0	0	-9999	-10000	0	0
FYN	0	0	-9999	-10000	0	0
ITGA3	-0.08	0.095	-9999	-10000	0	0
RELN/VLDLR/Fyn	-0.46	0.49	-9999	-0.98	17	17
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.024	0.14	-9999	-0.87	1	1
AKT1	-0.34	0.33	-9999	-0.59	21	21
MAP2K7	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
DAB1	-0.4	0.6	-9999	-1.3	11	11
RELN/LRP8/DAB1	-0.71	0.65	-9999	-1.2	21	21
LRPAP1/LRP8	-0.025	0.047	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.68	0.62	-9999	-1.1	21	21
DAB1/alpha3/beta1 Integrin	-0.63	0.57	-9999	-1.1	21	21
long-term memory	-0.68	0.59	-9999	-1.1	21	21
DAB1/LIS1	-0.63	0.6	-9999	-1.1	21	21
DAB1/CRLK/C3G	-0.6	0.57	-9999	-1	21	21
PIK3CA	0	0	-9999	-10000	0	0
DAB1/NCK2	-0.63	0.6	-9999	-1.1	21	21
ARHGEF2	0	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.12	0.094	-9999	-10000	0	0
CDK5R1	-0.005	0.032	-9999	-10000	0	0
RELN	-0.62	0.65	-9999	-1.3	17	17
PIK3R1	0	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.48	0.49	-9999	-1	17	17
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.7	0.64	-9999	-1.2	21	21
MAPK8	-0.036	0.22	-9999	-1.3	1	1
RELN/VLDLR/DAB1	-0.7	0.66	-9999	-1.2	21	21
ITGB1	0	0	-9999	-10000	0	0
MAP1B	-0.64	0.59	-9999	-1.1	21	21
RELN/LRP8	-0.48	0.49	-9999	-1	17	17
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.68	0.62	-9999	-1.1	21	21
PI3K	0	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.047	0.056	-9999	-10000	0	0
RAP1A	-0.54	0.48	-9999	-0.92	21	21
PAFAH1B1	0	0	-9999	-10000	0	0
MAPK8IP1	0	0	-9999	-10000	0	0
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
neuron differentiation	-0.26	0.26	-9999	-0.56	12	12
neuron adhesion	-0.52	0.45	-9999	-0.94	15	15
LRP8	-0.043	0.08	-9999	-10000	0	0
GSK3B	-0.3	0.33	-9999	-0.82	7	7
RELN/VLDLR/DAB1/Fyn	-0.66	0.62	-9999	-1.1	21	21
MAP3K11	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.37	0.35	-9999	-0.63	21	21
CDK5	0	0	-9999	-10000	0	0
MAPT	0.039	0.063	-9999	-10000	0	0
neuron migration	-0.38	0.37	-9999	-0.68	21	21
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.26	0.26	-9999	-0.57	12	12
RELN/VLDLR	-0.45	0.46	-9999	-0.94	17	17

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.011	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.44	0.46	-10000	0	-0.92	17	17
regulation of S phase of mitotic cell cycle	-0.22	0.24	-10000	0	-0.47	17	17
GNAO1	-0.54	0.64	-10000	0	-1.3	15	15
HRAS	0	0	-10000	0	-10000	0	0
SHBG/T-DHT	-0.77	0.41	-10000	0	-1	28	28
PELP1	0	0	-10000	0	-10000	0	0
AKT1	0.011	0.003	-10000	0	-10000	0	0
MAP2K1	-0.32	0.39	-10000	0	-0.73	17	17
T-DHT/AR	-0.52	0.55	-10000	0	-1.1	17	17
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.007	1	1
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.48	0.5	-10000	0	-1	17	17
cell proliferation	-0.29	0.37	-10000	0	-0.67	17	17
PIK3CA	0	0	-10000	0	-10000	0	0
FOS	-0.17	0.29	-10000	0	-0.95	3	3
mol:Ca2+	-0.07	0.067	-10000	0	-0.12	21	21
MAPK3	-0.31	0.38	-10000	0	-0.71	17	17
MAPK1	-0.099	0.14	-10000	0	-0.36	2	2
PIK3R1	0	0	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.003	3	3
cAMP biosynthetic process	-0.71	0.4	-10000	0	-0.92	28	28
GNG2	0	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.001	-10000	0	-0.003	3	3
HRAS/GTP	-0.4	0.42	-10000	0	-0.84	17	17
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0	0	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.003	3	3
PI3K	0	0	-10000	0	-10000	0	0
apoptosis	0.17	0.25	0.65	3	-10000	0	3
T-DHT/AR/PELP1	-0.47	0.49	-10000	0	-0.99	17	17
HRAS/GDP	-0.45	0.47	-10000	0	-0.95	17	17
CREB1	-0.19	0.27	-10000	0	-0.72	3	3
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
AR	-0.62	0.65	-10000	0	-1.3	17	17
GNB1	0	0	-10000	0	-10000	0	0
RAF1	-0.35	0.41	-10000	0	-0.79	17	17
RAC1-CDC42/GDP	-0.43	0.45	-10000	0	-0.91	17	17
T-DHT/AR/PELP1/Src	-0.44	0.46	-10000	0	-0.93	17	17
MAP2K2	-0.32	0.39	-10000	0	-0.73	17	17
T-DHT/AR/PELP1/Src/PI3K	-0.22	0.24	-10000	0	-0.47	17	17
GNAZ	-0.032	0.072	-10000	0	-10000	0	0
SHBG	-1	0.54	-10000	0	-1.3	28	28
Gi family/GNB1/GNG2/GDP	-0.39	0.46	-10000	0	-0.91	15	15
mol:T-DHT	0	0.001	0.002	2	-0.002	1	3
RAC1	0	0	-10000	0	-10000	0	0
GNRH1	0.011	0.001	-10000	0	-10000	0	0
Gi family/GTP	-0.42	0.47	-10000	0	-0.87	16	16
CDC42	0	0	-10000	0	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.16	0.34	-9999	-0.65	12	12
CRKL	-0.26	0.37	-9999	-0.77	12	12
mol:DAG	-0.26	0.37	-9999	-0.79	12	12
HRAS	-0.2	0.29	-9999	-10000	0	0
MAPK8	-0.29	0.44	-9999	-0.88	13	13
RAP1A	-0.26	0.37	-9999	-0.77	12	12
GAB1	-0.26	0.37	-9999	-0.77	12	12
MAPK14	-0.26	0.43	-9999	-0.87	12	12
EPO	-0.42	0.62	-9999	-1.3	12	12
PLCG1	-0.27	0.39	-9999	-0.82	12	12
EPOR/TRPC2/IP3 Receptors	-0.006	0.027	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.34	0.46	-9999	-0.96	13	13
GAB1/SHC/GRB2/SOS1	-0.22	0.31	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.36	0.51	-9999	-1.1	12	12
IRS2	-0.26	0.37	-9999	-0.77	12	12
STAT1	-0.23	0.42	-9999	-0.81	12	12
STAT5B	-0.27	0.38	-9999	-0.82	12	12
cell proliferation	-0.27	0.42	-9999	-0.83	13	13
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.21	0.29	-9999	-10000	0	0
TEC	-0.26	0.37	-9999	-0.77	12	12
SOCS3	-0.036	0.22	-9999	-1.3	1	1
STAT1 (dimer)	-0.22	0.4	-9999	-0.78	12	12
JAK2	-0.015	0.021	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	-0.24	0.41	-9999	-0.82	12	12
EPO/EPOR	-0.36	0.51	-9999	-1.1	12	12
LYN	0	0	-9999	-10000	0	0
TEC/VAV2	-0.25	0.35	-9999	-0.74	12	12
elevation of cytosolic calcium ion concentration	-0.006	0.027	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.32	0.45	-9999	-0.95	12	12
mol:IP3	-0.26	0.37	-9999	-0.79	12	12
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.23	0.33	-9999	-0.69	12	12
SH2B3	-0.015	0.021	-9999	-10000	0	0
NFKB1	-0.26	0.43	-9999	-0.87	12	12
EPO/EPOR (dimer)/JAK2/SOCS3	-0.18	0.25	-9999	-0.51	13	13
PTPN6	-0.24	0.4	-9999	-0.81	12	12
TEC/VAV2/GRB2	-0.24	0.34	-9999	-0.71	12	12
EPOR	-0.006	0.027	-9999	-10000	0	0
INPP5D	-0.005	0.032	-9999	-10000	0	0
mol:GDP	-0.23	0.32	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
PLCG2	0	0	-9999	-10000	0	0
CRKL/CBL/C3G	-0.24	0.34	-9999	-0.71	12	12
VAV2	-0.26	0.37	-9999	-0.77	12	12
CBL	-0.26	0.37	-9999	-0.77	12	12
SHC/Grb2/SOS1	-0.24	0.34	-9999	-0.71	12	12
STAT5A	-0.27	0.38	-9999	-0.82	12	12
GRB2	0	0	-9999	-10000	0	0
STAT5 (dimer)	-0.2	0.39	-9999	-0.76	12	12
LYN/PLCgamma2	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
BTK	-0.25	0.37	-9999	-0.77	12	12
BCL2	-0.16	0.34	-9999	-0.65	12	12

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/GPIbA	-0.002	0.012	-9999	-10000	0	0
alphaM/beta2 Integrin/proMMP-9	-0.009	0.025	-9999	-10000	0	0
PLAUR	-0.005	0.032	-9999	-10000	0	0
HMGB1	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	0	0	-9999	-10000	0	0
AGER	-0.005	0.031	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
SELPLG	0	0	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.001	0.011	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.021	0.061	-9999	-10000	0	0
CYR61	-0.036	0.22	-9999	-1.3	1	1
TLN1	0	0	-9999	-10000	0	0
Rap1/GTP	-0.52	0.34	-9999	-0.68	27	27
RHOA	0	0	-9999	-10000	0	0
P-selectin oligomer	-0.14	0.41	-9999	-1.3	4	4
MYH2	-0.88	0.5	-9999	-1.2	27	27
MST1R	-0.16	0.076	-9999	-10000	0	0
leukocyte activation during inflammatory response	-0.84	0.49	-9999	-1	29	29
APOB	-0.76	0.64	-9999	-1.3	21	21
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0	0	-9999	-10000	0	0
JAM3	0	0	-9999	-10000	0	0
GP1BA	-0.005	0.032	-9999	-10000	0	0
alphaM/beta2 Integrin/CTGF	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin	-0.63	0.43	-9999	-0.82	27	27
JAM3 homodimer	0	0	-9999	-10000	0	0
ICAM2	0	0	-9999	-10000	0	0
ICAM1	0	0	-9999	-10000	0	0
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.6	0.42	-9999	-0.8	27	27
cell adhesion	-0.002	0.012	-9999	-10000	0	0
NFKB1	-0.003	0.008	-9999	-10000	0	0
THY1	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.98	0.58	-9999	-1.2	29	29
alphaM/beta2 Integrin/LRP/tPA	-0.003	0.013	-9999	-10000	0	0
IL6	0.056	0.045	-9999	-10000	0	0
ITGB2	0	0	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	-0.007	0.028	-9999	-10000	0	0
alphaM/beta2 Integrin/JAM2/JAM3	0	0	-9999	-10000	0	0
JAM2	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/ICAM1	-0.63	0.44	-9999	-0.93	25	25
alphaM/beta2 Integrin/uPA/Plg	-0.46	0.46	-9999	-0.92	18	18
RhoA/GTP	-1	0.6	-9999	-1.3	28	28
positive regulation of phagocytosis	-0.4	0.27	-9999	-0.74	11	11
Ron/MSP	-0.83	0.49	-9999	-1.2	25	25
alphaM/beta2 Integrin/uPAR/uPA	-0.007	0.028	-9999	-10000	0	0
alphaM/beta2 Integrin/uPAR	-0.002	0.012	-9999	-10000	0	0
PLAU	-0.016	0.053	-9999	-10000	0	0
PLAT	-0.011	0.044	-9999	-10000	0	0
actin filament polymerization	-0.78	0.44	-9999	-1	27	27
MST1	-0.91	0.6	-9999	-1.3	25	25
alphaM/beta2 Integrin/lipoprotein(a)	-0.88	0.53	-9999	-1.1	29	29
TNF	0.06	0.037	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.006	0.02	-9999	-10000	0	0
fibrinolysis	-0.46	0.45	-9999	-0.91	18	18
HCK	0	0	-9999	-10000	0	0
dendritic cell antigen processing and presentation	-0.6	0.42	-9999	-0.8	27	27
VTN	-0.4	0.6	-9999	-1.3	11	11
alphaM/beta2 Integrin/CYR61	-0.027	0.16	-9999	-0.98	1	1
LPA	-0.58	0.65	-9999	-1.3	16	16
LRP1	0	0	-9999	-10000	0	0
cell migration	-0.007	0.019	-9999	-10000	0	0
FN1	-0.036	0.22	-9999	-1.3	1	1
alphaM/beta2 Integrin/Thy1	0	0	-9999	-10000	0	0
MPO	0	0	-9999	-10000	0	0
KNG1	-1	0.54	-9999	-1.3	28	28
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.87	0.5	-9999	-1.2	27	27
ELA2	0	0	-9999	-10000	0	0
PLG	-0.65	0.65	-9999	-1.3	18	18
CTGF	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/Hck	0	0	-9999	-10000	0	0
ITGAM	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.1	0.29	-9999	-0.91	4	4
HP	-1	0.54	-9999	-1.3	28	28
leukocyte adhesion	0.003	0.007	-9999	-10000	0	0
SELP	-0.14	0.41	-9999	-1.3	4	4

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0	0	-9999	-10000	0	0
VLDLR	-0.005	0.032	-9999	-10000	0	0
LRPAP1	0	0	-9999	-10000	0	0
NUDC	0	0	-9999	-10000	0	0
RELN/LRP8	-0.48	0.49	-9999	-1	17	17
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.44	0.46	-9999	-0.93	17	17
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.4	0.6	-9999	-1.3	11	11
IQGAP1	0	0	-9999	-10000	0	0
PLA2G7	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
DYNLT1	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.025	0.047	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0	0	-9999	-10000	0	0
CDK5R1	-0.005	0.032	-9999	-10000	0	0
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.021	0.061	-9999	-10000	0	0
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.74	0.69	-9999	-1.3	21	21
YWHAE	0	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.33	0.35	-9999	-0.71	17	17
MAP1B	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.39	0.41	-9999	-0.82	17	17
RELN	-0.62	0.65	-9999	-1.3	17	17
PAFAH/LIS1	0	0	-9999	-10000	0	0
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.25	0.27	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.46	0.54	-9999	-0.8	21	21
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.37	0.39	-9999	-0.77	17	17
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.022	0	-9999	-10000	0	0
PAFAH1B3	-0.005	0.032	-9999	-10000	0	0
PAFAH1B2	0	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0	0	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.32	0.34	-9999	-0.67	17	17
LRP8	-0.043	0.08	-9999	-10000	0	0
NDEL1/Katanin 60	-0.33	0.35	-9999	-0.71	17	17
P39/CDK5	-0.4	0.42	-9999	-0.83	17	17
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.4	0.45	-9999	-0.87	17	17
PPP2R5D	0	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.66	0.62	-9999	-1.1	21	21
RELN/VLDLR	-0.45	0.46	-9999	-0.94	17	17
CDC42	0	0	-9999	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.19	0.43	-9999	-1.1	6	6
EPHB2	-0.064	0.091	-9999	-10000	0	0
Syndecan-2/TACI	-0.16	0.37	-9999	-0.99	6	6
LAMA1	-0.021	0.061	-9999	-10000	0	0
Syndecan-2/alpha2 ITGB1	-0.14	0.34	-9999	-0.9	6	6
HRAS	0	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.16	0.37	-9999	-0.98	6	6
ITGA5	0	0	-9999	-10000	0	0
BAX	-0.14	0.36	-9999	-0.88	7	7
EPB41	0	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.15	0.34	-9999	-0.91	6	6
LAMA3	-0.016	0.053	-9999	-10000	0	0
EZR	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0	0	-9999	-10000	0	0
Syndecan-2/MMP2	-0.16	0.36	-9999	-0.98	6	6
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.056	0.056	-9999	-10000	0	0
dendrite morphogenesis	-0.19	0.36	-9999	-0.99	6	6
Syndecan-2/GM-CSF	-0.16	0.37	-9999	-0.98	6	6
determination of left/right symmetry	-0.16	0.41	-9999	-1.1	6	6
Syndecan-2/PKC delta	-0.16	0.36	-9999	-0.98	6	6
GNB2L1	0	0	-9999	-10000	0	0
MAPK3	-0.13	0.35	-9999	-0.91	6	6
MAPK1	-0.13	0.35	-9999	-0.91	6	6
Syndecan-2/RACK1	-0.15	0.33	-9999	-0.88	6	6
NF1	0	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	-0.16	0.41	-9999	-1.1	6	6
ITGA2	-0.096	0.096	-9999	-10000	0	0
MAPK8	-0.16	0.4	-9999	-0.97	7	7
Syndecan-2/alpha2/beta1 Integrin	-0.14	0.34	-9999	-0.9	6	6
Syndecan-2/Kininogen	-0.91	0.53	-9999	-1.1	29	29
ITGB1	0	0	-9999	-10000	0	0
SRC	-0.14	0.31	-9999	-0.82	6	6
Syndecan-2/CASK/Protein 4.1	-0.15	0.34	-9999	-0.92	6	6
extracellular matrix organization	-0.16	0.36	-9999	-0.97	6	6
actin cytoskeleton reorganization	-0.18	0.43	-9999	-1.1	6	6
Syndecan-2/Caveolin-2/Ras	-0.15	0.34	-9999	-0.91	6	6
Syndecan-2/Laminin alpha3	-0.17	0.36	-9999	-0.98	6	6
Syndecan-2/RasGAP	-0.14	0.31	-9999	-0.84	6	6
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
PRKCD	0	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.19	0.37	-9999	-1	6	6
GO:0007205	0	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.14	0.3	-9999	-0.81	6	6
RHOA	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
TNFRSF13B	-0.005	0.032	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.056	0.056	-9999	-10000	0	0
Syndecan-2/Synbindin	-0.16	0.36	-9999	-0.98	6	6
TGFB1	0	0	-9999	-10000	0	0
CASP3	-0.12	0.35	-9999	-0.9	6	6
FN1	-0.036	0.22	-9999	-1.3	1	1
Syndecan-2/IL8	-0.2	0.44	-9999	-1.1	6	6
SDC2	-0.16	0.41	-9999	-1.1	6	6
KNG1	-1	0.54	-9999	-1.3	28	28
Syndecan-2/Neurofibromin	-0.16	0.36	-9999	-0.98	6	6
TRAPPC4	0	0	-9999	-10000	0	0
CSF2	0	0	-9999	-10000	0	0
Syndecan-2/TGFB1	-0.16	0.36	-9999	-0.98	6	6
Syndecan-2/Syntenin/PI-4-5-P2	-0.15	0.34	-9999	-0.92	6	6
Syndecan-2/Ezrin	-0.15	0.34	-9999	-0.91	6	6
PRKACA	-0.12	0.35	-9999	-0.9	6	6
angiogenesis	-0.2	0.43	-9999	-1.1	6	6
MMP2	0	0	-9999	-10000	0	0
IL8	-0.068	0.22	-9999	-1.3	1	1
calcineurin-NFAT signaling pathway	-0.16	0.37	-9999	-0.98	6	6

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	0	0	-9999	-10000	0	0
Necdin/E2F1	-0.041	0.054	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.24	0.43	-9999	-0.96	9	9
NGF (dimer)/p75(NTR)/BEX1	-0.42	0.67	-9999	-1.4	11	11
NT-4/5 (dimer)/p75(NTR)	-0.28	0.47	-9999	-1.1	9	9
IKBKB	0	0	-9999	-10000	0	0
AKT1	-0.23	0.42	-9999	-0.93	9	9
IKBKG	0	0	-9999	-10000	0	0
BDNF	-0.021	0.061	-9999	-10000	0	0
MGDIs/NGR/p75(NTR)/LINGO1	-0.26	0.43	-9999	-1	9	9
FURIN	0	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.25	0.42	-9999	-0.98	9	9
LINGO1	-0.037	0.076	-9999	-10000	0	0
Sortilin/TRAF6/NRIF	0	0	-9999	-10000	0	0
proBDNF (dimer)	-0.021	0.06	-9999	-10000	0	0
NTRK1	0	0	-9999	-10000	0	0
RTN4R	0	0	-9999	-10000	0	0
neuron apoptosis	-0.18	0.38	-9999	-0.84	9	9
IRAK1	0	0	-9999	-10000	0	0
SHC1	-0.27	0.48	-9999	-1.1	9	9
ARHGDIA	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.25	0.45	-9999	-1	9	9
MAGEH1	-0.005	0.032	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.25	0.45	-9999	-1	9	9
Mammalian IAPs/DIABLO	-0.002	0.01	-9999	-10000	0	0
proNGF (dimer)	-0.036	0.21	-9999	-1.3	1	1
MAGED1	0	0	-9999	-10000	0	0
APP	0	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.011	0.044	-9999	-10000	0	0
ZNF274	0	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.24	0.42	-9999	-0.94	9	9
NGF	-0.036	0.22	-9999	-1.3	1	1
cell cycle arrest	-0.22	0.43	-9999	-0.93	9	9
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.13	0.24	-9999	-0.52	9	9
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.25	0.42	-9999	-0.98	9	9
NCSTN	0	0	-9999	-10000	0	0
mol:GTP	-0.26	0.47	-9999	-1.1	9	9
PSENEN	0	0	-9999	-10000	0	0
mol:ceramide	-0.24	0.44	-9999	-0.97	9	9
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.099	0.18	-9999	-0.72	1	1
p75(NTR)/beta APP	-0.27	0.47	-9999	-1.1	9	9
BEX1	-0.22	0.49	-9999	-1.3	6	6
mol:GDP	-0.25	0.49	-9999	-1.1	9	9
NGF (dimer)	-0.53	0.51	-9999	-1	18	18
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.24	0.41	-9999	-0.94	9	9
PIK3R1	0	0	-9999	-10000	0	0
RAC1/GTP	-0.24	0.43	-9999	-0.96	9	9
MYD88	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.27	0.48	-9999	-1.1	9	9
RHOB	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.041	0.054	-9999	-10000	0	0
NT3 (dimer)	-0.36	0.58	-9999	-1.3	10	10
TP53	-0.21	0.35	-9999	-0.82	9	9
PRDM4	-0.25	0.44	-9999	-0.99	9	9
BDNF (dimer)	-0.52	0.48	-9999	-1	18	18
PIK3CA	0	0	-9999	-10000	0	0
SORT1	0	0	-9999	-10000	0	0
activation of caspase activity	-0.23	0.42	-9999	-0.93	9	9
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.25	0.45	-9999	-1	9	9
RHOC	0	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
MAPK10	-0.13	0.33	-9999	-0.69	9	9
DIABLO	0	0	-9999	-10000	0	0
SMPD2	-0.25	0.44	-9999	-0.99	9	9
APH1B	0	0	-9999	-10000	0	0
APH1A	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.27	0.48	-9999	-1.1	9	9
PSEN1	0	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.54	0.72	-9999	-1.4	14	14
MAPK8	-0.14	0.33	-9999	-0.69	9	9
MAPK9	-0.13	0.33	-9999	-0.69	9	9
APAF1	0	0	-9999	-10000	0	0
NTF3	-0.36	0.58	-9999	-1.3	10	10
NTF4	-0.011	0.044	-9999	-10000	0	0
NDN	0	0	-9999	-10000	0	0
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.22	0.4	-9999	-0.89	9	9
p75 CTF/Sortilin/TRAF6/NRIF	0	0	-9999	-10000	0	0
RhoA-B-C/GTP	-0.26	0.47	-9999	-1	9	9
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.21	0.38	-9999	-0.87	9	9
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.24	0.39	-9999	-0.92	9	9
PRKACB	0	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.013	0.035	-9999	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.005	0.032	-9999	-10000	0	0
BIRC2	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.2	0.41	-9999	-0.88	9	9
BAD	-0.12	0.31	-9999	-0.66	9	9
RIPK2	0	0	-9999	-10000	0	0
NGFR	-0.33	0.57	-9999	-1.3	9	9
CYCS	-0.24	0.42	-9999	-0.94	9	9
ADAM17	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.25	0.45	-9999	-1	9	9
BCL2L11	-0.12	0.31	-9999	-0.66	9	9
BDNF (dimer)/p75(NTR)	-0.28	0.46	-9999	-1.1	9	9
PI3K	-0.25	0.45	-9999	-1	9	9
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.25	0.45	-9999	-1	9	9
NDNL2	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
PRKCI	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.3	0.53	-9999	-1.2	9	9
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.25	0.45	-9999	-1	9	9
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
PLG	-0.65	0.65	-9999	-1.3	18	18
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.25	0.44	-9999	-0.98	9	9
SQSTM1	0	0	-9999	-10000	0	0
NGFRAP1	0	0	-9999	-10000	0	0
CASP3	-0.1	0.28	-9999	-0.59	9	9
E2F1	-0.07	0.093	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
IKK complex	-0.09	0.2	-9999	-1	1	1
NGF (dimer)/TRKA	-0.03	0.18	-9999	-1.1	1	1
MMP7	-0.12	0.093	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.24	0.43	-9999	-0.96	9	9
MMP3	-0.005	0.032	-9999	-10000	0	0
APAF-1/Caspase 9	-0.17	0.29	-9999	-0.96	1	1

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.029	0.16	-9999	-0.98	1	1
fibroblast growth factor receptor signaling pathway	-0.029	0.16	-9999	-0.97	1	1
LAMA1	-0.021	0.061	-9999	-10000	0	0
PRNP	0	0	-9999	-10000	0	0
GPC1/SLIT2	-0.003	0.019	-9999	-10000	0	0
SMAD2	0	0	-9999	-10000	0	0
GPC1/PrPc/Cu2+	0	0	-9999	-10000	0	0
GPC1/Laminin alpha1	-0.013	0.035	-9999	-10000	0	0
TDGF1	-0.25	0.52	-9999	-1.3	7	7
CRIPTO/GPC1	-0.21	0.43	-9999	-1.1	7	7
APP/GPC1	0	0	-9999	-10000	0	0
mol:NO	0	0	-9999	-10000	0	0
YES1	-0.19	0.38	-9999	-0.97	7	7
FLT1	0	0	-9999	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0	0	-9999	-10000	0	0
SERPINC1	-1.1	0.45	-9999	-1.3	31	31
FYN	-0.19	0.38	-9999	-0.97	7	7
FGR	-0.19	0.38	-9999	-0.97	7	7
positive regulation of MAPKKK cascade	-0.14	0.38	-9999	-0.91	7	7
SLIT2	-0.005	0.032	-9999	-10000	0	0
GPC1/NRG	-0.21	0.43	-9999	-1.1	7	7
NRG1	-0.25	0.52	-9999	-1.3	7	7
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0	0	-9999	-10000	0	0
LYN	-0.19	0.38	-9999	-0.97	7	7
mol:Spermine	0.011	0	-9999	-10000	0	0
cell growth	-0.029	0.16	-9999	-0.97	1	1
BMP signaling pathway	0	0	-9999	-10000	0	0
SRC	-0.19	0.38	-9999	-0.97	7	7
TGFBR1	0	0	-9999	-10000	0	0
mol:Cu2+	0	0	-9999	-10000	0	0
PLA2G2A	-0.73	0.65	-9999	-1.3	20	20
GPC1	0	0	-9999	-10000	0	0
TGFBR1 (dimer)	0	0	-9999	-10000	0	0
VEGFA	0	0	-9999	-10000	0	0
BLK	-0.19	0.39	-9999	-0.98	7	7
HCK	-0.19	0.38	-9999	-0.97	7	7
FGF2	-0.036	0.22	-9999	-1.3	1	1
FGFR1	-0.005	0.032	-9999	-10000	0	0
VEGFR1 homodimer	0	0	-9999	-10000	0	0
TGFBR2	0	0	-9999	-10000	0	0
cell death	0	0	-9999	-10000	0	0
ATIII/GPC1	-0.93	0.38	-9999	-1.1	31	31
PLA2G2A/GPC1	-0.6	0.54	-9999	-1.1	20	20
LCK	-0.19	0.38	-9999	-0.97	7	7
neuron differentiation	-0.21	0.43	-9999	-1.1	7	7
PrPc/Cu2+	0	0	-9999	-10000	0	0
APP	0	0	-9999	-10000	0	0
TGFBR2 (dimer)	0	0	-9999	-10000	0	0

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0	0	-9999	-10000	0	0
ARNO/beta Arrestin1-2	-0.35	0.37	-9999	-0.75	17	17
EGFR	-0.073	0.3	-9999	-1.3	2	2
EPHA2	0	0	-9999	-10000	0	0
USP6	0	0	-9999	-10000	0	0
IQSEC1	0	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.069	0.26	-9999	-1.1	2	2
ARRB2	0	0	-9999	-10000	0	0
mol:GTP	0.021	0.002	-9999	-10000	0	0
ARRB1	0	0	-9999	-10000	0	0
FBXO8	0	0	-9999	-10000	0	0
TSHR	0	0	-9999	-10000	0	0
EGF	-0.016	0.053	-9999	-10000	0	0
somatostatin receptor activity	0	0	-9999	-0.001	16	16
ARAP2	0	0	-9999	-10000	0	0
mol:GDP	-0.16	0.16	-9999	-0.33	16	16
mol:PI-3-4-5-P3	0	0	-9999	-0.001	12	12
ITGA2B	-0.021	0.061	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0	0	-9999	-10000	0	0
ADAP1	0	0	-9999	-10000	0	0
KIF13B	0	0	-9999	-10000	0	0
HGF/MET	-0.18	0.4	-9999	-1.1	6	6
PXN	0	0	-9999	-10000	0	0
ARF6/GTP	-0.16	0.17	-9999	-0.32	16	16
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.061	0.23	-9999	-1	2	2
ADRB2	-0.62	0.65	-9999	-1.3	17	17
receptor agonist activity	0	0	-9999	0	16	16
actin filament binding	0	0	-9999	-0.001	16	16
SRC	0	0	-9999	-10000	0	0
ITGB3	0	0	-9999	-10000	0	0
GNAQ	0	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	-9999	-0.001	16	16
ARF6/GDP	-0.016	0.067	-9999	-10000	0	0
ARF6/GDP/GULP/ACAP1	-0.16	0.16	-9999	-10000	0	0
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.007	0.02	-9999	-10000	0	0
ACAP1	-0.005	0.032	-9999	-10000	0	0
ACAP2	0	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	0	0	-9999	-10000	0	0
EFNA1	0	0	-9999	-10000	0	0
HGF	-0.22	0.49	-9999	-1.3	6	6
CYTH3	0.011	0	-9999	-10000	0	0
CYTH2	0.005	0.003	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	16	16
endosomal lumen acidification	0	0	-9999	-0.001	5	5
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.096	0.096	-9999	-10000	0	0
GNAQ/ARNO	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	2	2
MET	0	0	-9999	-10000	0	0
GNA14	-0.073	0.3	-9999	-1.3	2	2
GNA15	0	0	-9999	-10000	0	0
GIT1	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	16	16
GNA11	0	0	-9999	-10000	0	0
LHCGR	0	0	-9999	-10000	0	0
AGTR1	-0.54	0.64	-9999	-1.3	15	15
desensitization of G-protein coupled receptor protein signaling pathway	0	0	-9999	-10000	0	0
IPCEF1/ARNO	-0.05	0.19	-9999	-0.83	2	2
alphaIIb/beta3 Integrin	-0.013	0.036	-9999	-10000	0	0

×

S1P5 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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.17	0.21	0.42	15	-10000	0	15
GNAI2	0	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.54	0.64	-10000	0	-1.3	15	15
RhoA/GTP	-0.18	0.21	-10000	0	-0.45	3	3
negative regulation of cAMP metabolic process	-0.2	0.23	-10000	0	-0.47	15	15
GNAZ	-0.032	0.072	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNA12	0	0	-10000	0	-10000	0	0
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.2	0.24	-10000	0	-0.48	15	15
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
GNAI1	0	0	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.03	0.18	-9999	-1.1	1	1
alphaV beta3 Integrin	-0.027	0.16	-9999	-0.98	1	1
PTK2	-0.11	0.24	-9999	-0.67	1	1
IGF1R	-0.005	0.032	-9999	-10000	0	0
PI4KB	0	0	-9999	-10000	0	0
MFGE8	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
CDKN1B	-0.28	0.41	-9999	-0.9	11	11
VEGFA	0	0	-9999	-10000	0	0
ILK	-0.28	0.41	-9999	-0.9	11	11
ROCK1	0	0	-9999	-10000	0	0
AKT1	-0.26	0.38	-9999	-0.84	11	11
PTK2B	-0.024	0.14	-9999	-0.86	1	1
alphaV/beta3 Integrin/JAM-A	-0.29	0.41	-9999	-0.87	12	12
CBL	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.68	0.45	-9999	-0.98	25	25
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.49	0.46	-9999	-0.92	19	19
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.12	0.17	-9999	-10000	0	0
alphaV/beta3 Integrin/Syndecan-1	-0.027	0.16	-9999	-0.98	1	1
PI4KA	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.46	0.43	-9999	-0.84	20	20
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.059	0.036	-9999	-10000	0	0
RPS6KB1	-0.43	0.39	-9999	-0.77	20	20
TLN1	0	0	-9999	-10000	0	0
MAPK3	-0.23	0.22	-9999	-1.3	1	1
GPR124	0	0	-9999	-10000	0	0
MAPK1	-0.23	0.22	-9999	-1.3	1	1
PXN	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.005	0.019	-9999	-10000	0	0
cell adhesion	-0.49	0.32	-9999	-0.7	25	25
ANGPTL3	-0.91	0.6	-9999	-1.3	25	25
VEGFR2 homodimer/VEGFA homodimer/Src	-0.027	0.16	-9999	-0.98	1	1
IGF-1R heterotetramer	-0.005	0.032	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0	0	-9999	-10000	0	0
ITGB3	0	0	-9999	-10000	0	0
IGF1	-0.69	0.65	-9999	-1.3	19	19
RAC1	0	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	0	0	-9999	-10000	0	0
apoptosis	0	0	-9999	-10000	0	0
CD47	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	0	0	-9999	-10000	0	0
VCL	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.014	0.03	-9999	-10000	0	0
CSF1	0	0	-9999	-10000	0	0
PIK3C2A	-0.28	0.41	-9999	-0.9	11	11
PI4 Kinase/Pyk2	-0.27	0.35	-9999	-0.74	11	11
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.025	0.15	-9999	-0.92	1	1
FAK1/Vinculin	-0.076	0.2	-9999	-10000	0	0
alphaV beta3/Integrin/ppsTEM5	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
VTN	-0.4	0.6	-9999	-1.3	11	11
BCAR1	0	0	-9999	-10000	0	0
FGF2	-0.036	0.22	-9999	-1.3	1	1
F11R	-0.008	0.18	-9999	-1.1	1	1
alphaV/beta3 Integrin/Lactadherin	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/TGFBR2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.036	0.22	-9999	-1.3	1	1
alphaV/beta3 Integrin/Pyk2	-0.024	0.14	-9999	-0.86	1	1
SDC1	-0.036	0.22	-9999	-1.3	1	1
VAV3	0.011	0.021	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
IRS1	0	0	-9999	-10000	0	0
FAK1/Paxillin	-0.076	0.2	-9999	-10000	0	0
cell migration	-0.059	0.18	-9999	-10000	0	0
ITGAV	0	0	-9999	-10000	0	0
PI3K	-0.26	0.37	-9999	-0.79	12	12
SPP1	-0.14	0.086	-9999	-10000	0	0
KDR	-0.036	0.22	-9999	-1.3	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0	0	-9999	-10000	0	0
COL4A3	-0.011	0.044	-9999	-10000	0	0
angiogenesis	-0.25	0.27	-9999	-0.79	4	4
Rac1/GTP	0.012	0.022	-9999	-10000	0	0
EDIL3	-0.032	0.072	-9999	-10000	0	0
cell proliferation	0	0	-9999	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.003	0.007	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.39	0.42	0.96	8	-10000	0	8
IL27/IL27R/JAK1	-0.65	0.51	-10000	0	-0.97	24	24
TBX21	-0.38	0.34	-10000	0	-0.8	6	6
IL12B	0	0	-10000	0	-10000	0	0
IL12A	0.007	0.022	-10000	0	-10000	0	0
IL6ST	-0.14	0.42	-10000	0	-1.3	4	4
IL27RA/JAK1	-0.017	0.015	-10000	0	-10000	0	0
IL27	-0.87	0.62	-10000	0	-1.3	24	24
TYK2	0.007	0.005	-10000	0	-10000	0	0
T-helper cell lineage commitment	0.02	0.025	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.39	0.42	0.96	8	-10000	0	8
T cell proliferation during immune response	0.39	0.42	0.96	8	-10000	0	8
MAPKKK cascade	-0.39	0.42	-10000	0	-0.96	8	8
STAT3	0	0	-10000	0	-10000	0	0
STAT2	0	0	-10000	0	-10000	0	0
STAT1	0	0	-10000	0	-10000	0	0
IL12RB1	-0.005	0.032	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.37	0.33	-10000	0	-0.73	7	7
IL27/IL27R/JAK2/TYK2	-0.4	0.44	-10000	0	-1	8	8
positive regulation of T cell mediated cytotoxicity	-0.39	0.42	-10000	0	-0.96	8	8
STAT1 (dimer)	-0.61	0.47	-10000	0	-1.2	7	7
JAK2	0.001	0.004	-10000	0	-10000	0	0
JAK1	0	0	-10000	0	-10000	0	0
STAT2 (dimer)	-0.38	0.39	-10000	0	-1.2	5	5
T cell proliferation	-0.38	0.4	-10000	0	-1.2	5	5
IL12/IL12R/TYK2/JAK2	0.009	0.026	-10000	0	-10000	0	0
IL17A	0.02	0.025	-10000	0	-10000	0	0
mast cell activation	0.39	0.42	0.96	8	-10000	0	8
IFNG	-0.037	0.039	-10000	0	-0.092	5	5
T cell differentiation	-0.012	0.009	-10000	0	-0.024	5	5
STAT3 (dimer)	-0.38	0.39	-10000	0	-1.2	5	5
STAT5A (dimer)	-0.38	0.39	-10000	0	-1.2	5	5
STAT4 (dimer)	-0.38	0.39	-10000	0	-1.2	5	5
STAT4	0	0	-10000	0	-10000	0	0
T cell activation	-0.021	0.01	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.11	0.31	-10000	0	-0.96	4	4
GATA3	0.08	0.063	-10000	0	-10000	0	0
IL18	-0.019	0.057	-10000	0	-10000	0	0
positive regulation of mast cell cytokine production	-0.37	0.37	-10000	0	-1.1	5	5
IL27/EBI3	-0.75	0.55	-10000	0	-1.1	24	24
IL27RA	-0.022	0.029	-10000	0	-10000	0	0
IL6	-0.014	0.054	-10000	0	-10000	0	0
STAT5A	0	0	-10000	0	-10000	0	0
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	0.022	0.018	-10000	0	-10000	0	0
IL1B	0.008	0.022	-10000	0	-10000	0	0
EBI3	-0.035	0.22	-10000	0	-1.3	1	1
TNF	0.007	0.022	-10000	0	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.29	0.39	-9999	-0.8	9	9
CRP	-0.35	0.48	-9999	-0.98	10	10
cell cycle arrest	-0.36	0.46	-9999	-0.99	9	9
TIMP1	-0.23	0.32	-9999	-0.65	8	8
IL6ST	-0.14	0.42	-9999	-1.3	4	4
Rac1/GDP	-0.15	0.26	-9999	-0.75	5	5
AP1	-0.072	0.22	-9999	-0.73	3	3
GAB2	0.006	0.012	-9999	-10000	0	0
TNFSF11	-0.35	0.48	-9999	-1	10	10
HSP90B1	-0.016	0.068	-9999	-10000	0	0
GAB1	0.004	0.009	-9999	-10000	0	0
MAPK14	-0.095	0.26	-9999	-0.81	3	3
AKT1	0.034	0.034	-9999	-10000	0	0
FOXO1	0.054	0.019	-9999	-10000	0	0
MAP2K6	-0.099	0.28	-9999	-0.67	6	6
mol:GTP	-0.003	0.004	-9999	-10000	0	0
MAP2K4	-0.16	0.31	-9999	-0.8	5	5
MITF	-0.12	0.29	-9999	-0.76	5	5
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0	0	-9999	-10000	0	0
A2M	-0.29	0.7	-9999	-1.9	6	6
CEBPB	0.012	0.009	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.023	0.084	-9999	-10000	0	0
STAT3	-0.38	0.5	-9999	-1.1	9	9
STAT1	-0.01	0.023	-9999	-10000	0	0
CEBPD	-0.29	0.39	-9999	-0.8	9	9
PIK3CA	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
JUN	0	0	-9999	-10000	0	0
PIAS3/MITF	-0.13	0.25	-9999	-0.76	4	4
MAPK11	-0.095	0.26	-9999	-0.81	3	3
STAT3 (dimer)/FOXO1	-0.27	0.4	-9999	-0.76	10	10
GRB2/SOS1/GAB family	-0.065	0.22	-9999	-0.78	2	2
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.1	0.26	-9999	-0.7	5	5
GRB2	0.004	0.009	-9999	-10000	0	0
JAK2	0	0	-9999	-10000	0	0
LBP	-0.56	0.58	-9999	-1.1	19	19
PIK3R1	0	0	-9999	-10000	0	0
JAK1	0.001	0.006	-9999	-10000	0	0
MYC	-0.29	0.39	-9999	-0.8	9	9
FGG	-0.67	0.68	-9999	-1.3	20	20
macrophage differentiation	-0.36	0.46	-9999	-0.99	9	9
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.18	0.44	-9999	-1.2	5	5
JUNB	-0.28	0.37	-9999	-0.77	9	9
FOS	-0.11	0.36	-9999	-1.3	3	3
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.13	0.3	-9999	-0.81	5	5
STAT1/PIAS1	-0.18	0.26	-9999	-0.77	5	5
GRB2/SOS1/GAB family/SHP2/PI3K	0.011	0.025	-9999	-10000	0	0
STAT3 (dimer)	-0.38	0.5	-9999	-1.1	9	9
PRKCD	-0.2	0.34	-9999	-0.84	5	5
IL6R	-0.11	0.36	-9999	-1.3	3	3
SOCS3	-0.066	0.31	-9999	-0.97	3	3
gp130 (dimer)/JAK1/JAK1/LMO4	-0.11	0.32	-9999	-1	4	4
Rac1/GTP	-0.18	0.27	-9999	-0.79	5	5
HCK	0.002	0.006	-9999	-10000	0	0
MAPKKK cascade	0.015	0.086	-9999	-10000	0	0
bone resorption	-0.32	0.44	-9999	-0.91	10	10
IRF1	-0.29	0.39	-9999	-0.8	9	9
mol:GDP	-0.12	0.29	-9999	-0.77	5	5
SOS1	0.005	0.012	-9999	-10000	0	0
VAV1	-0.13	0.3	-9999	-0.79	5	5
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.09	0.28	-9999	-0.66	6	6
PTPN11	-0.012	0.023	-9999	-10000	0	0
IL6/IL6RA	-0.1	0.3	-9999	-1.1	3	3
gp130 (dimer)/TYK2/TYK2/LMO4	-0.11	0.31	-9999	-1	4	4
gp130 (dimer)/JAK2/JAK2/LMO4	-0.11	0.31	-9999	-1	4	4
IL6	-0.011	0.057	-9999	-10000	0	0
PIAS3	0	0	-9999	-10000	0	0
PTPRE	0.019	0.018	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.12	0.26	-9999	-0.72	5	5
LMO4	0.007	0.012	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.4	0.4	-9999	-0.97	9	9
MCL1	0.053	0.02	-9999	-10000	0	0

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.54	0.64	-9999	-1.3	15	15
CDC42/GTP	-0.18	0.21	-9999	-0.45	3	3
PLCG1	-0.18	0.22	-9999	-0.44	15	15
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.17	0.21	-9999	-0.44	3	3
S1PR5	0	0	-9999	-10000	0	0
S1PR4	-0.005	0.032	-9999	-10000	0	0
MAPK3	-0.18	0.22	-9999	-10000	0	0
MAPK1	-0.18	0.22	-9999	-0.44	15	15
S1P/S1P5/Gi	-0.2	0.24	-9999	-0.48	15	15
GNAI1	0	0	-9999	-10000	0	0
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	0	0	-9999	-10000	0	0
RHOA	-0.002	0.009	-9999	-10000	0	0
S1P/S1P4/Gi	-0.2	0.24	-9999	-0.48	15	15
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.032	0.072	-9999	-10000	0	0
S1P/S1P4/G12/G13	-0.002	0.012	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0	0	-9999	-10000	0	0
SVIL	0	0	-9999	-10000	0	0
ZNF318	0	0	-9999	-10000	0	0
JMJD2C	0	0	-9999	-10000	0	0
T-DHT/AR/Ubc9	-0.46	0.48	-9999	-0.97	17	17
CARM1	0	0	-9999	-10000	0	0
PRDX1	0	0	-9999	-10000	0	0
PELP1	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
PTK2B	0	0	-9999	-10000	0	0
MED1	0	0	-9999	-10000	0	0
MAK	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0	0	-9999	-10000	0	0
GSN	0	0	-9999	-10000	0	0
NCOA2	-0.073	0.3	-9999	-1.3	2	2
NCOA6	0	0	-9999	-10000	0	0
DNA-PK	0	0	-9999	-10000	0	0
NCOA4	0	0	-9999	-10000	0	0
PIAS3	0	0	-9999	-10000	0	0
cell proliferation	-0.054	0.058	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
UBE3A	0	0	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.46	0.48	-9999	-0.97	17	17
FHL2	-0.12	0.12	-9999	-10000	0	0
RANBP9	0	0	-9999	-10000	0	0
JMJD1A	0.011	0.028	-9999	-0.16	1	1
CDK6	0	0	-9999	-10000	0	0
TGFB1I1	0	0	-9999	-10000	0	0
T-DHT/AR/CyclinD1	-0.46	0.48	-9999	-0.97	17	17
XRCC6	0	0	-9999	-10000	0	0
T-DHT/AR	-0.44	0.5	-9999	-0.96	17	17
CTDSP1	0	0	-9999	-10000	0	0
CTDSP2	0	0	-9999	-10000	0	0
BRCA1	0	0	-9999	-10000	0	0
TCF4	0	0	-9999	-10000	0	0
CDKN2A	-0.037	0.076	-9999	-10000	0	0
SRF	0.018	0	-9999	-10000	0	0
NKX3-1	-0.13	0.13	-9999	-10000	0	0
KLK3	0.002	0.005	-9999	-10000	0	0
TMF1	0	0	-9999	-10000	0	0
HNRNPA1	0	0	-9999	-10000	0	0
AOF2	0	0	-9999	-10000	0	0
APPL1	0.022	0	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.46	0.48	-9999	-0.97	17	17
AR	-0.6	0.65	-9999	-1.3	17	17
UBA3	0	0	-9999	-10000	0	0
PATZ1	0	0	-9999	-10000	0	0
PAWR	0	0	-9999	-10000	0	0
PRKDC	0	0	-9999	-10000	0	0
PA2G4	0	0	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.44	0.45	-9999	-0.92	17	17
RPS6KA3	0	0	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.46	0.48	-9999	-0.97	17	17
LATS2	0	0	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.44	0.46	-9999	-0.92	17	17
Cyclin D3/CDK11 p58	-0.003	0.021	-9999	-10000	0	0
VAV3	-0.043	0.08	-9999	-10000	0	0
KLK2	-0.14	0.14	-9999	-10000	0	0
CASP8	0	0	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.48	0.53	-9999	-1	17	17
TMPRSS2	-0.16	0.27	-9999	-1.6	1	1
CCND1	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
mol:T-DHT	0.002	0.014	-9999	-0.08	1	1
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0	0	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.46	0.48	-9999	-0.97	17	17
CMTM2	0	0	-9999	-10000	0	0
SNURF	0	0	-9999	-10000	0	0
ZMIZ1	0.007	0.014	-9999	-10000	0	0
CCND3	-0.005	0.032	-9999	-10000	0	0
TGIF1	0	0	-9999	-10000	0	0
FKBP4	0	0	-9999	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.12	0.26	-10000	0	-0.92	3	3
IHH	-0.12	0.37	-10000	0	-1.4	3	3
SHH Np/Cholesterol/GAS1	0	0	-10000	0	-10000	0	0
LRPAP1	0	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0	0	-10000	0	-10000	0	0
SMO/beta Arrestin2	-0.093	0.24	-10000	0	-0.84	3	3
SMO	-0.1	0.26	-10000	0	-0.9	3	3
AKT1	-0.032	0.09	-10000	0	-10000	0	0
ARRB2	0	0	-10000	0	-10000	0	0
BOC	0	0	-10000	0	-10000	0	0
ADRBK1	0	0	-10000	0	-10000	0	0
heart looping	-0.085	0.26	-10000	0	-0.88	3	3
STIL	-0.064	0.21	-10000	0	-0.74	3	3
DHH N/PTCH2	0	0	-10000	0	-10000	0	0
DHH N/PTCH1	-0.093	0.24	-10000	0	-0.88	3	3
PIK3CA	0	0	-10000	0	-10000	0	0
DHH	0	0	-10000	0	-10000	0	0
PTHLH	-0.14	0.27	-10000	0	-0.98	3	3
determination of left/right symmetry	-0.085	0.26	-10000	0	-0.88	3	3
PIK3R1	0	0	-10000	0	-10000	0	0
skeletal system development	-0.14	0.27	-10000	0	-0.97	3	3
IHH N/Hhip	-0.46	0.59	-10000	0	-1.2	14	14
DHH N/Hhip	-0.36	0.51	-10000	0	-1.1	12	12
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.085	0.26	-10000	0	-0.88	3	3
pancreas development	-0.43	0.61	-10000	0	-1.3	12	12
HHAT	0	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0	0	-10000	0	-10000	0	0
somite specification	-0.085	0.26	-10000	0	-0.88	3	3
SHH Np/Cholesterol/PTCH1	-0.08	0.22	-10000	0	-0.79	3	3
SHH Np/Cholesterol/PTCH2	0	0	-10000	0	-10000	0	0
SHH Np/Cholesterol/Megalin	-0.18	0.36	-10000	0	-0.92	7	7
SHH	0.022	0.002	-10000	0	-10000	0	0
catabolic process	-0.099	0.26	-10000	0	-0.95	3	3
SMO/Vitamin D3	-0.085	0.23	-10000	0	-0.82	3	3
SHH Np/Cholesterol/Hhip	-0.31	0.44	-10000	0	-0.92	12	12
LRP2	-0.26	0.52	-10000	0	-1.3	7	7
receptor-mediated endocytosis	-0.16	0.31	-10000	0	-1	3	3
SHH Np/Cholesterol/BOC	0	0	-10000	0	-10000	0	0
SHH Np/Cholesterol/CDO	0	0	-10000	0	-10000	0	0
mesenchymal cell differentiation	0.3	0.43	0.91	12	-10000	0	12
mol:Vitamin D3	-0.068	0.23	-10000	0	-0.81	3	3
IHH N/PTCH2	-0.082	0.28	-10000	0	-1	3	3
CDON	0	0	-10000	0	-10000	0	0
IHH N/PTCH1	-0.099	0.27	-10000	0	-0.97	3	3
Megalin/LRPAP1	-0.21	0.43	-10000	0	-1.1	7	7
PTCH2	0	0	-10000	0	-10000	0	0
SHH Np/Cholesterol	0	0	-10000	0	-10000	0	0
PTCH1	-0.1	0.26	-10000	0	-0.95	3	3
HHIP	-0.44	0.62	-10000	0	-1.3	12	12

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0	0	-9999	-10000	0	0
GNB1/GNG2	-0.04	0.073	-9999	-10000	0	0
AKT1	0.016	0.11	-9999	-10000	0	0
EGF	-0.016	0.053	-9999	-10000	0	0
mol:TXA2	0	0.001	-9999	-10000	0	0
FGR	0	0	-9999	-10000	0	0
mol:Ca2+	-0.001	0.16	-9999	-0.29	8	8
LYN	0	0	-9999	-10000	0	0
RhoA/GTP	-0.027	0.05	-9999	-10000	0	0
mol:PGI2	0	0	-9999	-10000	0	0
SYK	-0.006	0.18	-9999	-0.34	8	8
GNG2	0	0	-9999	-10000	0	0
ARRB2	0	0	-9999	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.026	0.06	-9999	-10000	0	0
G beta5/gamma2	-0.051	0.093	-9999	-10000	0	0
PRKCH	-0.008	0.18	-9999	-0.34	7	7
DNM1	-0.032	0.072	-9999	-10000	0	0
TXA2/TP beta/beta Arrestin3	-0.003	0.015	-9999	-10000	0	0
mol:GTP	0	0.001	-9999	-10000	0	0
PTGDR	0	0	-9999	-10000	0	0
G12 family/GTP	-0.067	0.12	-9999	-0.3	8	8
ADRBK1	0	0	-9999	-10000	0	0
ADRBK2	0	0	-9999	-10000	0	0
RhoA/GTP/ROCK1	0	0	-9999	-10000	0	0
mol:GDP	-0.015	0.091	-9999	-10000	0	0
mol:NADP	0	0	-9999	-10000	0	0
RAB11A	0	0	-9999	-10000	0	0
PRKG1	0	0	-9999	-10000	0	0
mol:IP3	-0.012	0.19	-9999	-0.36	8	8
cell morphogenesis	0	0	-9999	-10000	0	0
PLCB2	-0.033	0.24	-9999	-0.49	8	8
mol:cGMP	0	0.001	-9999	-10000	0	0
BLK	0.002	0.01	-9999	-10000	0	0
mol:PDG2	0	0	-9999	-10000	0	0
HCK	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PTGIR	0	0	-9999	-10000	0	0
PRKCB1	-0.016	0.19	-9999	-0.37	8	8
GNAQ	0	0	-9999	-10000	0	0
mol:L-citrulline	0	0	-9999	-10000	0	0
TXA2/TXA2-R family	-0.038	0.26	-9999	-0.52	8	8
LCK	0.002	0.01	-9999	-10000	0	0
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0	0	-9999	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.007	0.013	-9999	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0	0	-9999	-10000	0	0
MAPK14	0.011	0.13	-9999	-10000	0	0
TGM2/GTP	-0.019	0.2	-9999	-0.4	8	8
MAPK11	0.011	0.13	-9999	-10000	0	0
ARHGEF1	0.007	0.097	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
JNK cascade	-0.014	0.2	-9999	-0.38	8	8
RAB11/GDP	0	0	-9999	-10000	0	0
ICAM1	-0.001	0.15	-9999	-0.28	8	8
cAMP biosynthetic process	-0.009	0.18	-9999	-0.33	8	8
Gq family/GTP/EBP50	-0.017	0.068	-9999	-0.3	2	2
actin cytoskeleton reorganization	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
GNB5	0	0	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
EGF/EGFR	0.056	0.049	-9999	-10000	0	0
VCAM1	-0.014	0.18	-9999	-0.34	8	8
TP beta/Gq family/GDP/G beta5/gamma2	0.026	0.06	-9999	-10000	0	0
platelet activation	0.013	0.17	-9999	-0.3	8	8
PGI2/IP	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
Gq family/GDP/G beta5/gamma2	0.024	0.06	-9999	-10000	0	0
TXA2/TP beta/beta Arrestin2	0.006	0.017	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TBXA2R	0	0	-9999	-10000	0	0
mol:DAG	-0.02	0.21	-9999	-0.41	8	8
EGFR	-0.073	0.3	-9999	-1.3	2	2
TXA2/TP alpha	-0.022	0.23	-9999	-0.45	8	8
Gq family/GTP	-0.021	0.085	-9999	-0.37	2	2
YES1	0	0	-9999	-10000	0	0
GNAI2/GTP	0	0	-9999	-10000	0	0
PGD2/DP	0	0	-9999	-10000	0	0
SLC9A3R1	0	0	-9999	-10000	0	0
FYN	0	0	-9999	-10000	0	0
mol:NO	0	0	-9999	-10000	0	0
GNA15	0	0	-9999	-10000	0	0
PGK/cGMP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0	0	-9999	-10000	0	0
NOS3	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
PRKCA	-0.008	0.18	-9999	-0.34	8	8
PRKCB	-0.02	0.2	-9999	-0.39	8	8
PRKCE	-0.007	0.18	-9999	-0.35	7	7
PRKCD	-0.016	0.2	-9999	-0.38	8	8
PRKCG	-0.017	0.19	-9999	-0.38	8	8
muscle contraction	-0.029	0.24	-9999	-0.48	8	8
PRKCZ	-0.004	0.18	-9999	-0.34	8	8
ARR3	0	0	-9999	-10000	0	0
TXA2/TP beta	0	0	-9999	-10000	0	0
PRKCQ	-0.023	0.2	-9999	-0.36	9	9
MAPKKK cascade	-0.024	0.22	-9999	-0.43	8	8
SELE	-0.033	0.21	-9999	-0.42	8	8
TP beta/GNAI2/GDP/G beta/gamma	0	0	-9999	-10000	0	0
ROCK1	0	0	-9999	-10000	0	0
GNA14	-0.073	0.3	-9999	-1.3	2	2
chemotaxis	-0.061	0.31	-9999	-0.64	8	8
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	0	0	-9999	-10000	0	0
Rac1/GTP	0	0	-9999	-10000	0	0

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.36	0.37	-10000	0	-1.1	6	6
STAT6 (cleaved dimer)	-0.37	0.36	-10000	0	-1.1	6	6
IGHG1	-0.23	0.16	-10000	0	-0.41	10	10
IGHG3	-0.36	0.36	-10000	0	-1	6	6
AKT1	-0.15	0.17	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.11	0.12	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.16	0.17	-10000	0	-10000	0	0
THY1	-0.36	0.37	-10000	0	-1.1	6	6
MYB	-0.021	0.061	-10000	0	-10000	0	0
HMGA1	-0.021	0.061	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.21	0.2	-10000	0	-0.54	6	6
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.16	0.17	-10000	0	-10000	0	0
SP1	0.018	0.003	-10000	0	-10000	0	0
INPP5D	-0.005	0.032	-10000	0	-10000	0	0
SOCS5	0.02	0.012	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.35	0.36	-10000	0	-1	6	6
SOCS1	-0.23	0.25	-10000	0	-0.8	2	2
SOCS3	-0.2	0.27	-10000	0	-1.4	1	1
FCER2	-0.27	0.27	-10000	0	-0.87	2	2
PARP14	0.001	0.004	-10000	0	-10000	0	0
CCL17	-0.37	0.38	-10000	0	-1.1	6	6
GRB2	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.13	0.14	-10000	0	-10000	0	0
T cell proliferation	-0.34	0.37	-10000	0	-1	6	6
IL4R/JAK1	-0.36	0.37	-10000	0	-1	6	6
EGR2	-0.36	0.37	-10000	0	-1.1	6	6
JAK2	-0.003	0.019	-10000	0	-10000	0	0
JAK3	0.009	0.035	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
JAK1	0.002	0.007	-10000	0	-10000	0	0
COL1A2	-0.12	0.12	-10000	0	-10000	0	0
CCL26	-0.37	0.37	-10000	0	-1.1	6	6
IL4R	-0.39	0.39	-10000	0	-1.1	6	6
PTPN6	0.022	0.009	-10000	0	-10000	0	0
IL13RA2	-0.97	0.79	-10000	0	-1.7	19	19
IL13RA1	-0.003	0.019	-10000	0	-10000	0	0
IRF4	-0.059	0.077	-10000	0	-10000	0	0
ARG1	-1.2	0.86	-10000	0	-1.8	24	24
CBL	-0.19	0.19	-10000	0	-0.6	1	1
GTF3A	0.018	0.003	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.01	0.031	-10000	0	-10000	0	0
IRF4/BCL6	-0.054	0.058	-10000	0	-10000	0	0
CD40LG	0.012	0.038	-10000	0	-10000	0	0
MAPK14	-0.19	0.19	-10000	0	-0.6	1	1
mitosis	-0.14	0.16	-10000	0	-10000	0	0
STAT6	-0.4	0.43	-10000	0	-1.2	6	6
SPI1	-0.079	0.066	-10000	0	-10000	0	0
RPS6KB1	-0.13	0.16	-10000	0	-10000	0	0
STAT6 (dimer)	-0.4	0.43	-10000	0	-1.2	6	6
STAT6 (dimer)/PARP14	-0.38	0.39	-10000	0	-1.1	6	6
mast cell activation	0.011	0.009	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.15	0.16	-10000	0	-10000	0	0
FRAP1	-0.15	0.17	-10000	0	-10000	0	0
LTA	-0.37	0.38	-10000	0	-1.1	6	6
FES	0	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.4	0.42	1.2	6	-10000	0	6
CCL11	-0.35	0.36	-10000	0	-1	6	6
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.15	0.16	-10000	0	-10000	0	0
IL2RG	0.009	0.035	-10000	0	-10000	0	0
IL10	-0.36	0.37	-10000	0	-1.1	6	6
IRS1	0	0	-10000	0	-10000	0	0
IRS2	0	0	-10000	0	-10000	0	0
IL4	-0.1	0.093	-10000	0	-10000	0	0
IL5	-0.37	0.37	-10000	0	-1.1	6	6
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.31	0.3	-10000	0	-0.83	6	6
COL1A1	-0.13	0.13	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.36	0.37	-10000	0	-1.1	6	6
IL2R gamma/JAK3	-0.008	0.041	-10000	0	-10000	0	0
TFF3	-0.37	0.37	-10000	0	-1.1	6	6
ALOX15	-0.37	0.37	-10000	0	-1.1	6	6
MYBL1	0	0	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.31	0.3	-10000	0	-0.83	6	6
SHC1	0	0	-10000	0	-10000	0	0
CEBPB	-0.079	0.066	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.16	0.16	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.15	0.17	-10000	0	-10000	0	0
PI3K	-0.15	0.17	-10000	0	-10000	0	0
DOK2	0	0	-10000	0	-10000	0	0
ETS1	0.017	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.12	0.14	-10000	0	-10000	0	0
ITGB3	-0.36	0.37	-10000	0	-1.1	6	6
PIGR	-0.61	0.71	-10000	0	-1.7	10	10
IGHE	-0.001	0.032	-10000	0	-10000	0	0
MAPKKK cascade	-0.12	0.14	-10000	0	-10000	0	0
BCL6	0	0	-10000	0	-10000	0	0
OPRM1	-0.37	0.37	-10000	0	-1.1	6	6
RETNLB	-0.37	0.37	-10000	0	-1.1	6	6
SELP	-0.47	0.57	-10000	0	-1.4	8	8
AICDA	-0.36	0.36	-10000	0	-1	6	6

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.37	0.44	-9999	-0.88	15	15
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.021	0.061	-9999	-10000	0	0
SMAD9	-0.082	0.065	-9999	-10000	0	0
SMAD4	0	0	-9999	-10000	0	0
SMAD5	-0.13	0.19	-9999	-1	1	1
BMP7/USAG1	-0.016	0.039	-9999	-10000	0	0
SMAD5/SKI	-0.13	0.16	-9999	-0.95	1	1
SMAD1	0.043	0.021	-9999	-10000	0	0
BMP2	0	0	-9999	-10000	0	0
SMAD1/SMAD1/SMAD4	-0.001	0.005	-9999	-10000	0	0
BMPR1A	0	0	-9999	-10000	0	0
BMPR1B	-0.047	0.22	-9999	-1.3	1	1
BMPR1A-1B/BAMBI	-0.032	0.16	-9999	-0.98	1	1
AHSG	-1.1	0.49	-9999	-1.3	30	30
CER1	0	0	-9999	-10000	0	0
BMP2-4/CER1	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.28	0.21	-9999	-0.48	5	5
BMP2-4 (homodimer)	0	0	-9999	-10000	0	0
RGMB	0	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.029	0.15	-9999	-0.92	1	1
RGMA	-0.027	0.067	-9999	-10000	0	0
SMURF1	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.26	0.23	-9999	-0.39	24	24
BMP2-4/USAG1	-0.002	0.013	-9999	-10000	0	0
SMAD6/SMURF1/SMAD5	-0.13	0.16	-9999	-0.95	1	1
SOSTDC1	-0.005	0.032	-9999	-10000	0	0
BMP7/BMPR2/BMPR1A-1B	-0.036	0.15	-9999	-0.92	1	1
SKI	0	0	-9999	-10000	0	0
BMP6 (homodimer)	0	0	-9999	-10000	0	0
HFE2	-0.87	0.62	-9999	-1.3	24	24
ZFYVE16	0	0	-9999	-10000	0	0
MAP3K7	0	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.11	0.31	-9999	-0.98	4	4
SMAD5/SMAD5/SMAD4	-0.13	0.16	-9999	-0.95	1	1
MAPK1	0	0	-9999	-10000	0	0
TAK1/TAB family	-0.22	0.19	-9999	-0.97	1	1
BMP7 (homodimer)	-0.021	0.06	-9999	-10000	0	0
NUP214	0	0	-9999	-10000	0	0
BMP6/FETUA	-0.9	0.4	-9999	-1.1	30	30
SMAD1/SKI	-0.002	0.011	-9999	-10000	0	0
SMAD6	0	0	-9999	-10000	0	0
CTDSP2	0	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.82	0.36	-9999	-0.98	30	30
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.083	0.3	-9999	-1.3	2	2
BMPR2 (homodimer)	0	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.036	0.18	-9999	-1.1	1	1
CHRDL1	-0.073	0.3	-9999	-1.3	2	2
ENDOFIN/SMAD1	-0.002	0.011	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.001	0.008	-9999	-10000	0	0
SMAD6/SMURF1	0	0	-9999	-10000	0	0
BAMBI	0	0	-9999	-10000	0	0
SMURF2	0	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.054	0.22	-9999	-0.98	2	2
BMP2-4/GREM1	-0.059	0.22	-9999	-0.98	2	2
SMAD7	0	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.071	0.055	-9999	-10000	0	0
SMAD1/SMAD6	-0.002	0.011	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.021	0.061	-9999	-10000	0	0
BMP6	0	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.2	0.17	-9999	-0.81	1	1
PPM1A	0	0	-9999	-10000	0	0
SMAD1/SMURF2	-0.002	0.011	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0	0	-9999	-10000	0	0
PPP1CA	0	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
PPP1R15A	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.34	0.26	-9999	-0.62	15	15
CHRD	-0.14	0.41	-9999	-1.3	4	4
BMPR2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.26	0.23	-9999	-0.54	5	5
BMP4	0	0	-9999	-10000	0	0
FST	-0.51	0.64	-9999	-1.3	14	14
BMP2-4/NOG	-0.009	0.025	-9999	-10000	0	0
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.019	0.15	-9999	-0.87	1	1

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.03	0.18	-9999	-1.1	1	1
PDGFRB	0.001	0.003	-9999	-10000	0	0
SPHK1	-0.015	0.026	-9999	-10000	0	0
mol:S1P	-0.019	0.034	-9999	-10000	0	0
S1P1/S1P/Gi	-0.19	0.28	-9999	-0.51	15	15
GNAO1	-0.54	0.64	-9999	-1.3	15	15
PDGFB-D/PDGFRB/PLCgamma1	-0.17	0.21	-9999	-0.7	1	1
PLCG1	-0.16	0.26	-9999	-0.63	2	2
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.001	0.003	-9999	-10000	0	0
GNAI2	0	0.003	-9999	-10000	0	0
GNAI3	0.001	0.003	-9999	-10000	0	0
GNAI1	0.001	0.003	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.004	0.16	-9999	-0.96	1	1
S1P1/S1P	-0.019	0.12	-9999	-0.72	1	1
negative regulation of cAMP metabolic process	-0.18	0.28	-9999	-0.5	15	15
MAPK3	-0.17	0.28	-9999	-1	1	1
calcium-dependent phospholipase C activity	-0.002	0.002	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	-0.036	0.22	-9999	-1.3	1	1
PLCB2	0.004	0.11	-9999	-0.62	1	1
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.017	0.098	-9999	-0.58	1	1
receptor internalization	-0.021	0.11	-9999	-0.65	1	1
PTGS2	-0.16	0.29	-9999	-1.3	1	1
Rac1/GTP	-0.017	0.098	-9999	-0.58	1	1
RHOA	0	0	-9999	-10000	0	0
VEGFA	0	0	-9999	-10000	0	0
negative regulation of T cell proliferation	-0.18	0.28	-9999	-0.5	15	15
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.032	0.072	-9999	-10000	0	0
MAPK1	-0.17	0.28	-9999	-0.74	2	2
S1P1/S1P/PDGFB-D/PDGFRB	-0.024	0.12	-9999	-0.73	1	1
ABCC1	-0.006	0.033	-9999	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.12	0.23	-9999	-0.53	8	8
FZD6	0	0	-9999	-10000	0	0
WNT6	-0.005	0.032	-9999	-10000	0	0
WNT4	-0.036	0.22	-9999	-1.3	1	1
FZD3	0	0	-9999	-10000	0	0
WNT5A	0	0	-9999	-10000	0	0
WNT11	-0.29	0.54	-9999	-1.3	8	8

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0	0	-9999	-10000	0	0
mol:S1P	0.001	0.001	-9999	-10000	0	0
S1P1/S1P/Gi	-0.16	0.19	-9999	-0.38	15	15
GNAO1	-0.54	0.64	-9999	-1.3	15	15
S1P/S1P3/G12/G13	0	0	-9999	-10000	0	0
AKT1	-0.06	0.074	-9999	-10000	0	0
AKT3	-0.059	0.13	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0	0	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GNAI1	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0	0	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.17	0.25	-9999	-0.46	15	15
MAPK3	-0.15	0.24	-9999	-10000	0	0
MAPK1	-0.15	0.24	-9999	-0.43	15	15
JAK2	-0.15	0.23	-9999	-0.42	15	15
CXCR4	-0.16	0.24	-9999	-10000	0	0
FLT1	0.013	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	-0.15	0.24	-9999	-10000	0	0
S1P/S1P3/Gi	-0.17	0.25	-9999	-0.46	15	15
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.17	0.21	-9999	-10000	0	0
VEGFA	0.013	0	-9999	-10000	0	0
S1P/S1P2/Gi	-0.2	0.23	-9999	-0.47	15	15
VEGFR1 homodimer/VEGFA homodimer	0.01	0.011	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.026	0.11	-9999	-0.48	2	2
GNAQ	0	0	-9999	-10000	0	0
GNAZ	-0.032	0.071	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.073	0.3	-9999	-1.3	2	2
GNA15	0	0	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	0	0	-9999	-10000	0	0
Rac1/GTP	-0.17	0.21	-9999	-10000	0	0

×

Visual signal transduction: Rods

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
mol:K +	0	0	-9999	-10000	0	0
GNAT1/GTP	0	0	-9999	-10000	0	0
Metarhodopsin II/Arrestin	0	0	-9999	-10000	0	0
PDE6G/GNAT1/GTP	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
CNG Channel	-0.4	0.42	-9999	-0.84	17	17
mol:Na +	-0.38	0.4	-9999	-0.8	17	17
mol:ADP	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.005	0.021	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.4	0.42	-9999	-0.84	17	17
CNGB1	-0.021	0.061	-9999	-10000	0	0
RDH5	-0.4	0.6	-9999	-1.3	11	11
SAG	0	0	-9999	-10000	0	0
mol:Ca2+	-0.37	0.38	-9999	-0.77	17	17
Na + (4 Units)	-0.35	0.36	-9999	-0.74	17	17
RGS9	-0.011	0.044	-9999	-10000	0	0
GNB1/GNGT1	0	0	-9999	-10000	0	0
GNAT1/GDP	-0.004	0.016	-9999	-10000	0	0
GUCY2D	0	0	-9999	-10000	0	0
GNGT1	0	0	-9999	-10000	0	0
GUCY2F	0	0	-9999	-10000	0	0
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.006	0.019	-9999	-10000	0	0
mol:11-cis-retinal	-0.4	0.6	-9999	-1.3	11	11
mol:cGMP	0	0	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
Rhodopsin	-0.33	0.5	-9999	-1.1	11	11
SLC24A1	0	0	-9999	-10000	0	0
CNGA1	-0.62	0.65	-9999	-1.3	17	17
Metarhodopsin II	0	0	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0	0	-9999	-10000	0	0
RGS9BP	0	0	-9999	-10000	0	0
Metarhodopsin II/Transducin	0	0	-9999	-10000	0	0
GCAP Family/Ca ++	0	0	-9999	-10000	0	0
PDE6A/B	-0.01	0.032	-9999	-10000	0	0
mol:Pi	-0.005	0.021	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	0	0	-9999	-10000	0	0
PDE6B	-0.016	0.053	-9999	-10000	0	0
PDE6A	0	0	-9999	-10000	0	0
PDE6G	0	0	-9999	-10000	0	0
RHO	0	0	-9999	-10000	0	0
PDE6	-0.007	0.017	-9999	-10000	0	0
GUCA1A	0	0	-9999	-10000	0	0
GC2/GCAP Family	0	0	-9999	-10000	0	0
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0	0	-9999	-10000	0	0

×

Signaling events mediated by PRL

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.032	0.072	-9999	-10000	0	0
mol:Halofuginone	-0.007	0.042	-9999	-0.25	1	1
ITGA1	-0.036	0.22	-9999	-1.3	1	1
CDKN1A	-0.016	0.067	-9999	-0.32	1	1
PRL-3/alpha Tubulin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.12	0.34	-9999	-1.1	4	4
AGT	-0.14	0.41	-9999	-1.3	4	4
CCNA2	-0.033	0.28	-9999	-1.2	2	2
TUBA1B	0	0	-9999	-10000	0	0
EGR1	-0.02	0.2	-9999	-0.76	2	2
CDK2/Cyclin E1	-0.003	0.063	-9999	-10000	0	0
MAPK3	0.022	0	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0	-9999	-10000	0	0
MAPK1	0.022	0	-9999	-10000	0	0
PTP4A1	-0.031	0.3	-9999	-1.2	2	2
PTP4A3	0	0	-9999	-10000	0	0
PTP4A2	0	0	-9999	-10000	0	0
ITGB1	0.022	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
RAC1	-0.016	0.067	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.63	0.5	-9999	-0.95	24	24
RABGGTA	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RHOC	-0.016	0.067	-9999	-0.32	1	1
RHOA	-0.016	0.067	-9999	-10000	0	0
cell motility	0.017	0.081	-9999	-0.35	1	1
PRL-1/alpha Tubulin	-0.062	0.27	-9999	-1.1	2	2
PRL-3/alpha1 Integrin	-0.03	0.18	-9999	-1.1	1	1
ROCK1	0.017	0.082	-9999	-0.35	1	1
RABGGTB	0	0	-9999	-10000	0	0
CDK2	0	0	-9999	-10000	0	0
mitosis	-0.029	0.29	-9999	-1.2	2	2
ATF5	-0.87	0.62	-9999	-1.3	24	24

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.018	0.009	-9999	-10000	0	0
RAS family/GTP	-0.1	0.24	-9999	-1.2	1	1
NFATC4	-0.055	0.22	-9999	-0.61	1	1
ERBB2IP	0.004	0.007	-9999	-10000	0	0
HSP90 (dimer)	0	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.14	0.28	-9999	-0.71	7	7
JUN	0.03	0.075	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
DOCK7	-0.13	0.26	-9999	-0.66	7	7
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.19	0.41	-9999	-0.99	7	7
AKT1	0.01	0.005	-9999	-10000	0	0
BAD	0.019	0.005	-9999	-10000	0	0
MAPK10	-0.054	0.12	-9999	-0.34	1	1
mol:GTP	0	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.16	0.33	-9999	-0.81	7	7
RAF1	-0.037	0.23	-9999	-1	1	1
ErbB2/ErbB3/neuregulin 2	-0.039	0.16	-9999	-0.94	1	1
STAT3	-0.001	0.003	-9999	-10000	0	0
cell migration	-0.009	0.14	-9999	-0.33	2	2
mol:PI-3-4-5-P3	-0.001	0.004	-9999	-10000	0	0
cell proliferation	-0.006	0.2	-9999	-0.62	1	1
FOS	-0.013	0.21	-9999	-0.57	3	3
NRAS	0	0	-9999	-10000	0	0
mol:Ca2+	-0.14	0.28	-9999	-0.71	7	7
MAPK3	-0.006	0.19	-9999	-0.66	1	1
MAPK1	-0.006	0.19	-9999	-0.66	1	1
JAK2	-0.13	0.26	-9999	-0.66	7	7
NF2	-0.006	0.012	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.13	0.3	-9999	-0.65	7	7
NRG1	-0.25	0.52	-9999	-1.3	7	7
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.096	0.2	-9999	-0.49	7	7
MAPK9	-0.056	0.11	-9999	-0.34	1	1
ERBB2	0	0	-9999	-10000	0	0
ERBB3	-0.037	0.22	-9999	-1.3	1	1
SHC1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
apoptosis	-0.001	0.011	-9999	-10000	0	0
STAT3 (dimer)	-0.001	0.003	-9999	-10000	0	0
RNF41	0.024	0.012	-9999	-10000	0	0
FRAP1	0.009	0.004	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.083	0.17	-9999	-0.53	1	1
ErbB2/ErbB2/HSP90 (dimer)	0	0	-9999	-10000	0	0
CHRNA1	0.012	0.14	-9999	-0.41	1	1
myelination	-0.049	0.21	-9999	-0.6	1	1
PPP3CB	-0.12	0.24	-9999	-0.6	7	7
KRAS	0	0	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.11	0.26	-9999	-1.3	1	1
NRG2	-0.032	0.072	-9999	-10000	0	0
mol:GDP	-0.12	0.3	-9999	-0.64	7	7
SOS1	0	0	-9999	-10000	0	0
MAP2K2	-0.019	0.21	-9999	-0.87	1	1
SRC	0	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.003	-9999	-10000	0	0
PTPN11	-0.13	0.27	-9999	-0.66	7	7
MAP2K1	-0.025	0.2	-9999	-0.69	1	1
heart morphogenesis	-0.14	0.28	-9999	-0.71	7	7
RAS family/GDP	-0.1	0.25	-9999	-1.3	1	1
GRB2	0	0	-9999	-10000	0	0
PRKACA	-0.008	0.016	-9999	-10000	0	0
CHRNE	0.019	0.017	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
activation of caspase activity	-0.01	0.005	-9999	-10000	0	0
nervous system development	-0.14	0.28	-9999	-0.71	7	7
CDC42	0	0	-9999	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.029	0.064	-9999	-10000	0	0
TBX21	-0.046	0.37	-9999	-1.4	2	2
B2M	-0.002	0.009	-9999	-10000	0	0
TYK2	0.012	0.017	-9999	-10000	0	0
IL12RB1	0.006	0.039	-9999	-10000	0	0
GADD45B	-0.037	0.24	-9999	-0.78	2	2
IL12RB2	0.012	0.017	-9999	-10000	0	0
GADD45G	-0.61	0.8	-9999	-1.5	17	17
natural killer cell activation	0	0.02	-9999	-10000	0	0
RELB	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
IL18	-0.038	0.089	-9999	-10000	0	0
IL2RA	-0.016	0.053	-9999	-10000	0	0
IFNG	0	0	-9999	-10000	0	0
STAT3 (dimer)	-0.074	0.29	-9999	-0.96	2	2
HLA-DRB5	0	0	-9999	-10000	0	0
FASLG	-0.036	0.32	-9999	-1.2	2	2
NF kappa B2 p52/RelB	-0.12	0.29	-9999	-1.3	2	2
CD4	-0.036	0.22	-9999	-1.3	1	1
SOCS1	-0.005	0.032	-9999	-10000	0	0
EntrezGene:6955	-0.004	0.017	-9999	-10000	0	0
CD3D	-0.002	0.047	-9999	-10000	0	0
CD3E	0.003	0.035	-9999	-10000	0	0
CD3G	-0.034	0.23	-9999	-1.4	1	1
IL12Rbeta2/JAK2	0.02	0.028	-9999	-10000	0	0
CCL3	-0.096	0.48	-9999	-1.6	3	3
CCL4	-0.062	0.42	-9999	-1.7	2	2
HLA-A	-0.002	0.009	-9999	-10000	0	0
IL18/IL18R	-0.019	0.2	-9999	-1.1	1	1
NOS2	-0.04	0.27	-9999	-0.96	2	2
IL12/IL12R/TYK2/JAK2/SPHK2	0.03	0.062	-9999	-10000	0	0
IL1R1	-0.036	0.32	-9999	-1.2	2	2
IL4	0	0.02	-9999	-10000	0	0
JAK2	0.012	0.017	-9999	-10000	0	0
EntrezGene:6957	-0.004	0.017	-9999	-10000	0	0
TCR/CD3/MHC I/CD8	-0.073	0.41	-9999	-1.4	3	3
RAB7A	-0.17	0.35	-9999	-0.84	2	2
lysosomal transport	-0.16	0.34	-9999	-0.79	2	2
FOS	-0.11	0.46	-9999	-1.3	4	4
STAT4 (dimer)	-0.11	0.33	-9999	-1	2	2
STAT5A (dimer)	-0.12	0.29	-9999	-1.3	2	2
GZMA	-0.063	0.42	-9999	-1.7	2	2
GZMB	-0.038	0.33	-9999	-1.2	2	2
HLX	0	0	-9999	-10000	0	0
LCK	-0.049	0.36	-9999	-1.4	2	2
TCR/CD3/MHC II/CD4	-0.009	0.12	-9999	-0.49	1	1
IL2/IL2R	-0.008	0.03	-9999	-10000	0	0
MAPK14	-0.22	0.41	-9999	-0.65	16	16
CCR5	-0.04	0.24	-9999	-0.79	2	2
IL1B	0.006	0.039	-9999	-10000	0	0
STAT6	0.008	0.092	-9999	-10000	0	0
STAT4	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
STAT1	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
NFKB2	0	0	-9999	-10000	0	0
IL12B	0.008	0.021	-9999	-10000	0	0
CD8A	-0.002	0.009	-9999	-10000	0	0
CD8B	-0.002	0.009	-9999	-10000	0	0
T-helper 1 cell differentiation	0	0	-9999	-10000	0	0
natural killer cell mediated cytotoxicity	-0.029	0.064	-9999	-10000	0	0
IL2RB	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.095	0.3	-9999	-0.9	2	2
IL2RG	-0.005	0.032	-9999	-10000	0	0
IL12	0.014	0.038	-9999	-10000	0	0
STAT5A	0	0	-9999	-10000	0	0
CD247	0.003	0.035	-9999	-10000	0	0
IL2	0	0	-9999	-10000	0	0
SPHK2	0	0	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
IL12A	0.006	0.038	-9999	-10000	0	0
IL12/IL12R/TYK2/JAK2	-0.065	0.4	-9999	-1.6	2	2
MAP2K3	-0.2	0.4	-9999	-0.73	7	7
RIPK2	0	0	-9999	-10000	0	0
MAP2K6	-0.2	0.4	-9999	-0.61	16	16
regulation of dendritic cell antigen processing and presentation	0	0	-9999	-10000	0	0
HLA-DRA	0	0	-9999	-10000	0	0
IL18RAP	0.009	0.009	-9999	-10000	0	0
IL12Rbeta1/TYK2	0.011	0.034	-9999	-10000	0	0
EOMES	-0.13	0.49	-9999	-1.7	3	3
STAT1 (dimer)	-0.061	0.28	-9999	-0.93	2	2
T cell proliferation	-0.1	0.28	-9999	-0.62	3	3
T-helper 1 cell lineage commitment	0	0	-9999	-10000	0	0
IL18R1	-0.028	0.22	-9999	-1.3	1	1
CD8-positive alpha-beta T cell lineage commitment	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.23	0.26	-9999	-0.77	3	3
ATF2	-0.2	0.39	-9999	-0.81	4	4

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.001	0.003	-10000	0	-10000	0	0
epithelial cell differentiation	-0.098	0.22	-10000	0	-0.72	4	4
ITCH	0	0.003	-10000	0	-10000	0	0
WWP1	0.037	0.003	-10000	0	-10000	0	0
FYN	0	0	-10000	0	-10000	0	0
EGFR	-0.073	0.3	-10000	0	-1.3	2	2
PRL	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.08	0.31	-10000	0	-0.71	7	7
PTPRZ1	-0.011	0.044	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.16	0.32	-10000	0	-0.8	7	7
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.18	0.36	-10000	0	-0.92	7	7
ADAM17	0	0.003	-10000	0	-10000	0	0
ErbB4/ErbB4	0	0.002	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.031	0.16	-10000	0	-0.94	1	1
NCOR1	0	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.17	0.34	-10000	0	-0.87	7	7
GRIN2B	-0.16	0.33	-10000	0	-0.82	7	7
ErbB4/ErbB2/betacellulin	0.001	0.005	-10000	0	-10000	0	0
STAT1	0	0	-10000	0	-10000	0	0
HBEGF	0	0	-10000	0	-10000	0	0
PRLR	-0.14	0.41	-10000	0	-1.3	4	4
E4ICDs/ETO2	0.001	0.003	-10000	0	-10000	0	0
axon guidance	-0.013	0.099	-10000	0	-10000	0	0
NEDD4	0	0.003	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.12	0.34	-10000	0	-1.1	4	4
CBFA2T3	0	0	-10000	0	-10000	0	0
ErbB4/ErbB2/HBEGF	0.001	0.005	-10000	0	-10000	0	0
MAPK3	-0.14	0.29	-10000	0	-0.74	7	7
STAT1 (dimer)	0.001	0.003	-10000	0	-10000	0	0
MAPK1	-0.14	0.29	-10000	0	-0.74	7	7
JAK2	0	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.17	0.34	-10000	0	-0.87	7	7
NRG1	-0.2	0.44	-10000	0	-1.1	7	7
NRG3	-0.052	0.22	-10000	0	-1.3	1	1
NRG2	-0.032	0.072	-10000	0	-10000	0	0
NRG4	-0.073	0.3	-10000	0	-1.3	2	2
heart development	-0.013	0.099	-10000	0	-10000	0	0
neural crest cell migration	-0.16	0.34	-10000	0	-0.85	7	7
ERBB2	0.023	0	-10000	0	-10000	0	0
WWOX/E4ICDs	0.001	0.003	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.099	0.28	-10000	0	-0.89	4	4
apoptosis	0.005	0.083	0.48	1	-10000	0	1
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.01	0.025	-10000	0	-10000	0	0
ErbB4/ErbB2/epiregulin	0.008	0.02	-10000	0	-10000	0	0
ErbB4/ErbB4/betacellulin/betacellulin	0.001	0.003	-10000	0	-10000	0	0
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.092	0.26	-10000	0	-0.83	4	4
MDM2	0.042	0.003	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.17	0.35	-10000	0	-0.89	7	7
STAT5A	-0.004	0.094	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.21	0.46	-10000	0	-1.1	7	7
DLG4	0	0	-10000	0	-10000	0	0
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0	0	-10000	0	-10000	0	0
STAT5A (dimer)	-0.11	0.25	-10000	0	-0.8	4	4
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.038	0.077	-10000	0	-10000	0	0
LRIG1	0	0	-10000	0	-10000	0	0
EREG	-0.021	0.061	-10000	0	-10000	0	0
BTC	0	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.013	0.1	-10000	0	-10000	0	0
ERBB4	0	0.002	-10000	0	-10000	0	0
STAT5B	0	0	-10000	0	-10000	0	0
YAP1	0	0.002	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.048	0.2	-10000	0	-0.87	2	2
glial cell differentiation	0	0	-10000	0	-10000	0	0
WWOX	0	0	-10000	0	-10000	0	0
cell proliferation	-0.1	0.3	-10000	0	-0.72	7	7

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0	0	-9999	-10000	0	0
SPHK1	-0.032	0.072	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
mol:S1P	-0.005	0.01	-9999	-10000	0	0
GNAO1	-0.54	0.64	-9999	-1.3	15	15
mol:Sphinganine-1-P	0	0.05	-9999	-10000	0	0
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.002	0.004	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0	0	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.004	0.008	-9999	-10000	0	0
S1PR5	0	0	-9999	-10000	0	0
S1PR4	-0.005	0.032	-9999	-10000	0	0
GNAI1	0	0	-9999	-10000	0	0
S1P/S1P5/G12	0.001	0.001	-9999	-10000	0	0
S1P/S1P3/Gq	-0.02	0.081	-9999	-0.35	2	2
S1P/S1P4/Gi	-0.19	0.23	-9999	-0.46	15	15
GNAQ	0	0	-9999	-10000	0	0
GNAZ	-0.032	0.072	-9999	-10000	0	0
GNA14	-0.073	0.3	-9999	-1.3	2	2
GNA15	0	0	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	0	0	-9999	-10000	0	0
ABCC1	-0.005	0.032	-9999	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.073	0.3	-9999	-1.3	2	2
GNB1/GNG2	-0.1	0.21	-9999	-0.84	1	1
mol:DAG	-0.093	0.18	-9999	-0.74	1	1
PLCG1	-0.097	0.19	-9999	-0.78	1	1
YES1	-0.11	0.22	-9999	-0.87	1	1
FZD3	0	0	-9999	-10000	0	0
FZD6	0	0	-9999	-10000	0	0
G protein	-0.097	0.19	-9999	-0.79	1	1
MAP3K7	-0.032	0.18	-9999	-0.58	1	1
mol:Ca2+	-0.09	0.18	-9999	-0.71	1	1
mol:IP3	-0.093	0.18	-9999	-0.74	1	1
NLK	-0.005	0.009	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
CAMK2A	-0.044	0.19	-9999	-0.65	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.12	0.23	-9999	-0.53	8	8
CSNK1A1	0	0	-9999	-10000	0	0
GNAS	-0.11	0.22	-9999	-0.66	2	2
GO:0007205	-0.051	0.2	-9999	-0.72	1	1
WNT6	-0.005	0.032	-9999	-10000	0	0
WNT4	-0.036	0.22	-9999	-1.3	1	1
NFAT1/CK1 alpha	-0.14	0.24	-9999	-0.77	3	3
GNG2	0	0	-9999	-10000	0	0
WNT5A	0	0	-9999	-10000	0	0
WNT11	-0.29	0.54	-9999	-1.3	8	8
CDC42	-0.064	0.22	-9999	-0.82	1	1

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0	0	-9999	-10000	0	0
CRKL	-0.025	0.14	-9999	-10000	0	0
mol:PIP3	-0.02	0.007	-9999	-10000	0	0
AKT1	0.002	0.006	-9999	-10000	0	0
PTK2B	0	0	-9999	-10000	0	0
RAPGEF1	-0.015	0.14	-9999	-10000	0	0
RANBP10	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.16	0.36	-9999	-0.98	6	6
MAP3K5	-0.005	0.13	-9999	-10000	0	0
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.15	0.34	-9999	-0.92	6	6
AP1	-0.084	0.28	-9999	-1	3	3
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
apoptosis	-0.058	0.24	-9999	-0.84	3	3
STAT3 (dimer)	-0.072	0.16	-9999	-0.43	6	6
GAB1/CRKL/SHP2/PI3K	-0.05	0.11	-9999	-10000	0	0
INPP5D	-0.005	0.032	-9999	-10000	0	0
CBL/CRK	-0.054	0.12	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0	0	-9999	-10000	0	0
PTEN	0	0	-9999	-10000	0	0
ELK1	-0.003	0.016	-9999	-10000	0	0
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.041	0.092	-9999	-10000	0	0
PAK1	0.011	0.005	-9999	-10000	0	0
HGF/MET/RANBP10	-0.16	0.36	-9999	-0.98	6	6
HRAS	-0.097	0.22	-9999	-10000	0	0
DOCK1	-0.015	0.14	-9999	-10000	0	0
GAB1	-0.034	0.15	-9999	-0.37	6	6
CRK	-0.025	0.14	-9999	-10000	0	0
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.13	0.28	-9999	-0.76	6	6
JUN	0	0	-9999	-10000	0	0
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.057	0.13	-9999	-0.34	6	6
PIK3R1	0	0	-9999	-10000	0	0
cell morphogenesis	-0.008	0.18	-9999	-10000	0	0
GRB2/SHC	-0.048	0.11	-9999	-10000	0	0
FOS	-0.11	0.36	-9999	-1.3	3	3
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.003	0.016	-9999	-10000	0	0
HGF/MET/MUC20	-0.16	0.37	-9999	-0.99	6	6
cell migration	-0.048	0.11	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
MET/RANBP10	0	0	-9999	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.078	0.18	-9999	-0.47	6	6
MET/MUC20	0	0	-9999	-10000	0	0
RAP1B	-0.006	0.13	-9999	-10000	0	0
RAP1A	-0.006	0.13	-9999	-10000	0	0
HGF/MET/RANBP9	-0.16	0.36	-9999	-0.98	6	6
RAF1	-0.053	0.22	-9999	-10000	0	0
STAT3	-0.073	0.16	-9999	-0.44	6	6
cell proliferation	-0.053	0.25	-9999	-0.6	6	6
RPS6KB1	-0.019	0.042	-9999	-10000	0	0
MAPK3	-0.006	0.013	-9999	-10000	0	0
MAPK1	-0.006	0.013	-9999	-10000	0	0
RANBP9	0	0	-9999	-10000	0	0
MAPK8	-0.004	0.16	-9999	-0.63	1	1
SRC	-0.073	0.16	-9999	-10000	0	0
PI3K	-0.048	0.11	-9999	-10000	0	0
MET/Glomulin	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
MAP2K1	-0.041	0.2	-9999	-10000	0	0
MET	0	0	-9999	-10000	0	0
MAP4K1	-0.014	0.14	-9999	-10000	0	0
PTK2	0	0	-9999	-10000	0	0
MAP2K2	-0.041	0.2	-9999	-10000	0	0
BAD	0.011	0.005	-9999	-10000	0	0
MAP2K4	0.005	0.12	-9999	-10000	0	0
SHP2/GRB2/SOS1/GAB1	-0.051	0.11	-9999	-10000	0	0
INPPL1	0	0	-9999	-10000	0	0
PXN	0	0	-9999	-10000	0	0
SH3KBP1	0	0	-9999	-10000	0	0
HGS	-0.052	0.12	-9999	-10000	0	0
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.22	0.49	-9999	-1.3	6	6
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
PTPRJ	0	0	-9999	-10000	0	0
NCK/PLCgamma1	-0.056	0.12	-9999	-10000	0	0
PDPK1	-0.007	0.006	-9999	-10000	0	0
HGF/MET/SHIP	-0.17	0.36	-9999	-0.98	6	6

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.72	0.82	-10000	0	-1.6	16	16
SMARCC2	0	0	-10000	0	-10000	0	0
SMARCC1	0	0	-10000	0	-10000	0	0
TBX21	-0.014	0.32	-10000	0	-1.7	1	1
SUMO2	0	0	-10000	0	-10000	0	0
STAT1 (dimer)	0.018	0	-10000	0	-10000	0	0
FKBP4	0	0	-10000	0	-10000	0	0
FKBP5	0	0	-10000	0	-10000	0	0
GR alpha/HSP90/FKBP51/HSP90	0.005	0.11	-10000	0	-10000	0	0
PRL	0.035	0.094	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	-0.087	0.45	0.64	1	-0.84	5	6
RELA	-0.016	0.075	-10000	0	-10000	0	0
FGG	-0.71	0.75	-10000	0	-1.4	20	20
GR beta/TIF2	-0.07	0.3	-10000	0	-1.2	2	2
IFNG	-0.007	0.16	-10000	0	-10000	0	0
apoptosis	-0.58	0.35	-10000	0	-0.87	17	17
CREB1	-0.001	0.052	-10000	0	-10000	0	0
histone acetylation	0.058	0.13	-10000	0	-10000	0	0
BGLAP	0.059	0.13	-10000	0	-10000	0	0
GR/PKAc	0.007	0.1	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.026	0.14	-10000	0	-10000	0	0
SMARCD1	0	0	-10000	0	-10000	0	0
MDM2	-0.017	0.094	-10000	0	-10000	0	0
GATA3	0.007	0.035	-10000	0	-10000	0	0
AKT1	0.067	0.078	-10000	0	-10000	0	0
CSF2	0.031	0.1	-10000	0	-10000	0	0
GSK3B	0	0	-10000	0	-10000	0	0
NR1I3	-0.95	0.42	-10000	0	-1.1	30	30
CSN2	-0.13	0.23	-10000	0	-10000	0	0
BRG1/BAF155/BAF170/BAF60A	0	0	-10000	0	-10000	0	0
NFATC1	0	0	-10000	0	-10000	0	0
POU2F1	0	0	-10000	0	-10000	0	0
CDKN1A	0.068	0.015	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.011	0.005	-10000	0	-10000	0	0
SFN	-0.17	0.061	-10000	0	-10000	0	0
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.031	0.15	-10000	0	-10000	0	0
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.45	0.27	-10000	0	-0.75	12	12
JUN	-0.15	0.27	-10000	0	-1	1	1
IL4	0.039	0.13	-10000	0	-10000	0	0
CDK5R1	-0.006	0.033	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.32	0.36	-10000	0	-1.2	4	4
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.014	0.1	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)	-0.053	0.41	0.57	5	-0.6	5	10
NCOA2	-0.073	0.3	-10000	0	-1.3	2	2
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.096	0.36	-10000	0	-1.3	3	3
AP-1/NFAT1-c-4	-0.2	0.36	-10000	0	-1.1	4	4
AFP	-0.61	0.86	-10000	0	-1.7	13	13
SUV420H1	0	0	-10000	0	-10000	0	0
IRF1	-0.02	0.16	-10000	0	-10000	0	0
TP53	0.032	0	-10000	0	-10000	0	0
PPP5C	0	0	-10000	0	-10000	0	0
KRT17	-0.042	0.18	-10000	0	-10000	0	0
KRT14	0.002	0.1	-10000	0	-10000	0	0
TBP	0.02	0.001	-10000	0	-10000	0	0
CREBBP	0.011	0.017	-10000	0	-10000	0	0
HDAC1	0	0	-10000	0	-10000	0	0
HDAC2	0	0	-10000	0	-10000	0	0
AP-1	-0.2	0.36	-10000	0	-1.1	4	4
MAPK14	0	0	-10000	0	-10000	0	0
MAPK10	-0.006	0.034	-10000	0	-10000	0	0
MAPK11	0	0	-10000	0	-10000	0	0
KRT5	-0.019	0.16	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
NCOA1	-0.02	0.033	-10000	0	-10000	0	0
STAT1	0.018	0	-10000	0	-10000	0	0
CGA	0.002	0.34	-10000	0	-1.9	1	1
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.023	0.14	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
MAPK1	0	0	-10000	0	-10000	0	0
ICAM1	0.028	0.16	-10000	0	-10000	0	0
NFKB1	-0.016	0.075	-10000	0	-10000	0	0
MAPK8	-0.092	0.26	-10000	0	-1.2	1	1
MAPK9	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.63	0.4	-10000	0	-0.96	17	17
BAX	0.068	0.015	-10000	0	-10000	0	0
POMC	0.086	0.15	-10000	0	-10000	0	0
EP300	0.011	0.017	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	-0.024	0.36	0.66	1	-10000	0	1
proteasomal ubiquitin-dependent protein catabolic process	-0.021	0.074	-10000	0	-10000	0	0
SGK1	0.051	0.041	-10000	0	-10000	0	0
IL13	-0.008	0.14	-10000	0	-10000	0	0
IL6	0.022	0.16	-10000	0	-10000	0	0
PRKACG	0	0	-10000	0	-10000	0	0
IL5	-0.014	0.12	-10000	0	-10000	0	0
IL2	-0.013	0.16	-10000	0	-10000	0	0
CDK5	0	0	-10000	0	-10000	0	0
PRKACB	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
IL8	-0.028	0.32	-10000	0	-1.7	1	1
CDK5R1/CDK5	-0.003	0.021	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.021	0.087	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.021	0.33	0.6	1	-10000	0	1
SMARCA4	0	0	-10000	0	-10000	0	0
chromatin remodeling	-0.011	0.17	0.37	1	-10000	0	1
NF kappa B1 p50/RelA/Cbp	-0.001	0.1	-10000	0	-10000	0	0
JUN (dimer)	-0.15	0.26	-10000	0	-1	1	1
YWHAH	0	0	-10000	0	-10000	0	0
VIPR1	-0.66	0.88	-10000	0	-1.6	16	16
NR3C1	-0.035	0.2	0.45	1	-10000	0	1
NR4A1	0.012	0.008	-10000	0	-10000	0	0
TIF2/SUV420H1	-0.06	0.25	-10000	0	-1.1	2	2
MAPKKK cascade	-0.58	0.35	-10000	0	-0.87	17	17
cortisol/GR alpha (dimer)/Src-1	-0.1	0.37	0.65	1	-0.61	5	6
PBX1	0	0	-10000	0	-10000	0	0
POU1F1	0	0	-10000	0	-10000	0	0
SELE	-0.23	0.68	-10000	0	-1.7	6	6
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.011	0.17	0.37	1	-10000	0	1
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.021	0.33	0.6	1	-10000	0	1
mol:cortisol	-0.056	0.21	0.44	1	-0.3	7	8
MMP1	-0.06	0.091	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.018	0.11	-9999	-0.64	1	1
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	0	0	-9999	-10000	0	0
alpha4/beta7 Integrin/MAdCAM1	-0.034	0.15	-9999	-0.92	1	1
EPO	-0.44	0.62	-9999	-1.3	12	12
alpha4/beta7 Integrin	-0.03	0.18	-9999	-1.1	1	1
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.36	0.51	-9999	-1.1	12	12
lamellipodium assembly	-0.001	0.003	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
JAK2	-0.18	0.26	-9999	-0.55	12	12
PXN	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
MADCAM1	-0.027	0.067	-9999	-10000	0	0
cell adhesion	-0.034	0.15	-9999	-0.9	1	1
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
SRC	-0.05	0.21	-9999	-0.91	2	2
ITGB7	-0.036	0.22	-9999	-1.3	1	1
RAC1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.054	0.22	-9999	-0.98	2	2
p130Cas/Crk/Dock1	-0.043	0.18	-9999	-0.77	2	2
VCAM1	-0.073	0.3	-9999	-1.3	2	2
RHOA	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0	0	-9999	-10000	0	0
BCAR1	-0.008	0.2	-9999	-0.85	2	2
EPOR	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
GIT1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.001	0.003	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0	0	-9999	-10000	0	0
HDAC4	0	0	-9999	-10000	0	0
induction of apoptosis	0	0	-9999	-10000	0	0
regulation of S phase of mitotic cell cycle	0	0	-9999	-10000	0	0
CDKN1A	0	0	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
BAX	0	0	-9999	-10000	0	0
FOXO3	0	0	-9999	-10000	0	0
FOXO1	0	0	-9999	-10000	0	0
FOXO4	0	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
TAT	-1.1	0.49	-9999	-1.3	30	30
mol:Lysophosphatidic acid	0	0	-9999	-10000	0	0
MYOD1	0.011	0	-9999	-10000	0	0
PPARGC1A	-0.073	0.3	-9999	-1.3	2	2
FHL2	0	0	-9999	-10000	0	0
response to nutrient levels	0	0	-9999	-10000	0	0
KU70/SIRT1	0	0	-9999	-10000	0	0
HIST2H4A	0	0	-9999	-10000	0	0
SIRT1/FOXO3a	0	0	-9999	-10000	0	0
SIRT1	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0	-9999	-10000	0	0
SIRT1/Histone H1b	-0.001	0.004	-9999	-10000	0	0
apoptosis	0	0	-9999	-10000	0	0
SIRT1/PGC1A	-0.055	0.23	-9999	-0.99	2	2
p53/SIRT1	0	0	-9999	-10000	0	0
SIRT1/FOXO4	0	0	-9999	-10000	0	0
FOXO1/FHL2/SIRT1	0	0	-9999	-10000	0	0
HIST1H1E	-0.003	0.008	-9999	-10000	0	0
SIRT1/p300	0	0	-9999	-10000	0	0
muscle cell differentiation	0	0	-9999	-10000	0	0
TP53	0	0	-9999	-10000	0	0
KU70/SIRT1/BAX	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
MEF2D	0	0	-9999	-10000	0	0
HIV-1 Tat/SIRT1	-0.9	0.4	-9999	-1.1	30	30
ACSS2	0	0	-9999	-10000	0	0
SIRT1/PCAF/MYOD	0	0	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	-0.011	0.018	-10000	0	-10000	0	0
oxygen homeostasis	-0.002	0.02	-10000	0	-10000	0	0
TCEB2	0	0	-10000	0	-10000	0	0
TCEB1	0	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.034	0.044	-10000	0	-10000	0	0
EPO	-0.3	0.55	-10000	0	-1	12	12
FIH (dimer)	0.011	0.015	-10000	0	-10000	0	0
APEX1	-0.001	0.008	-10000	0	-10000	0	0
SERPINE1	-0.1	0.39	-10000	0	-1.1	3	3
FLT1	-0.011	0.036	-10000	0	-10000	0	0
ADORA2A	-0.061	0.28	-10000	0	-0.72	1	1
germ cell development	-0.045	0.26	-10000	0	-0.71	1	1
SLC11A2	-0.044	0.27	-10000	0	-0.74	1	1
BHLHE40	-0.044	0.27	-10000	0	-0.74	1	1
HIF1AN	0.011	0.015	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.11	0.13	-10000	0	-10000	0	0
ETS1	0.025	0.004	-10000	0	-10000	0	0
CITED2	-0.014	0.019	-10000	0	-10000	0	0
KDR	-0.052	0.28	-10000	0	-1.7	1	1
PGK1	-0.044	0.27	-10000	0	-0.74	1	1
SIRT1	0	0	-10000	0	-10000	0	0
response to hypoxia	-0.004	0.008	-10000	0	-10000	0	0
HIF2A/ARNT	-0.068	0.3	-10000	0	-0.9	1	1
EPAS1	0.002	0.12	-10000	0	-10000	0	0
SP1	0.018	0	-10000	0	-10000	0	0
ABCG2	-0.34	0.6	-10000	0	-1.1	14	14
EFNA1	-0.044	0.27	-10000	0	-0.74	1	1
FXN	-0.061	0.28	-10000	0	-0.72	1	1
POU5F1	-0.048	0.27	-10000	0	-0.74	1	1
neuron apoptosis	0.14	0.22	0.86	1	-10000	0	1
EP300	0	0	-10000	0	-10000	0	0
EGLN3	-0.035	0.092	-10000	0	-10000	0	0
EGLN2	0.011	0.015	-10000	0	-10000	0	0
EGLN1	0.011	0.015	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0	0	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	-0.002	0.008	-10000	0	-10000	0	0
SLC2A1	-0.07	0.29	-10000	0	-0.72	1	1
TWIST1	-0.065	0.29	-10000	0	-0.72	1	1
ELK1	0.018	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.065	0.098	-10000	0	-10000	0	0
VEGFA	-0.044	0.27	-10000	0	-0.74	1	1
CREBBP	0	0	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-1.1	0.84	-9999	-1.7	23	23
PLK1	-0.22	0.24	-9999	-0.84	2	2
CDKN1B	-0.1	0.14	-9999	-10000	0	0
FOXO3	-0.22	0.25	-9999	-0.89	2	2
KAT2B	0.016	0.007	-9999	-10000	0	0
FOXO1/SIRT1	-0.24	0.2	-9999	-10000	0	0
CAT	-0.25	0.39	-9999	-1.7	2	2
CTNNB1	0	0	-9999	-10000	0	0
AKT1	-0.013	0.029	-9999	-10000	0	0
FOXO1	-0.25	0.23	-9999	-0.43	23	23
MAPK10	0.02	0.022	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
FOXO4	0.068	0.067	-9999	-10000	0	0
response to oxidative stress	-0.03	0.036	-9999	-10000	0	0
FOXO3A/SIRT1	-0.23	0.21	-9999	-0.83	2	2
XPO1	0	0	-9999	-10000	0	0
EP300	-0.023	0.024	-9999	-10000	0	0
BCL2L11	-0.009	0.033	-9999	-10000	0	0
FOXO1/SKP2	-0.25	0.19	-9999	-10000	0	0
mol:GDP	-0.03	0.035	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
GADD45A	-0.03	0.1	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
FOXO1/14-3-3 family	-0.014	0.053	-9999	-10000	0	0
MST1	-0.9	0.61	-9999	-1.3	25	25
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
MAPK8	-0.002	0.15	-9999	-0.9	1	1
MAPK9	0.023	0.015	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
YWHAZ	0	0	-9999	-10000	0	0
SIRT1	0.013	0.007	-9999	-10000	0	0
SOD2	-0.16	0.2	-9999	-0.53	1	1
RBL2	-0.11	0.16	-9999	-10000	0	0
RAL/GDP	0.006	0.015	-9999	-10000	0	0
CHUK	0.018	0.008	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
RAL/GTP	0.013	0.019	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
FASLG	-0.009	0.033	-9999	-10000	0	0
SKP2	0	0	-9999	-10000	0	0
USP7	0	0	-9999	-10000	0	0
IKBKB	0.018	0.008	-9999	-10000	0	0
CCNB1	-0.2	0.24	-9999	-0.81	2	2
FOXO1-3a-4/beta catenin	-0.14	0.11	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.25	0.18	-9999	-10000	0	0
CSNK1A1	0	0	-9999	-10000	0	0
SGK1	0.016	0.007	-9999	-10000	0	0
CSNK1G3	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
ZFAND5	0.071	0.058	-9999	-10000	0	0
SFN	-0.17	0.061	-9999	-10000	0	0
CDK2	-0.04	0.041	-9999	-10000	0	0
FOXO3A/14-3-3	-0.025	0.022	-9999	-10000	0	0
CREBBP	-0.04	0.041	-9999	-10000	0	0
FBXO32	-0.2	0.23	-9999	-0.79	2	2
BCL6	-0.11	0.16	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.026	0.013	-9999	-10000	0	0
NFATC2	-0.029	0.23	-9999	-0.98	2	2
NFATC3	0.026	0.013	-9999	-10000	0	0
CD40LG	-0.093	0.25	-9999	-0.92	2	2
PTGS2	-0.1	0.29	-9999	-1.1	2	2
JUNB	0	0	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0	0.001	-9999	-10000	0	0
CaM/Ca2+	0	0.001	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
JUN	0	0	-9999	-10000	0	0
mol:Ca2+	-0.001	0.003	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-9999	-10000	0	0
FOSL1	-0.011	0.044	-9999	-10000	0	0
CREM	0	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.045	0.18	-9999	-0.79	2	2
FOS	-0.11	0.36	-9999	-1.3	3	3
IFNG	-0.071	0.26	-9999	-0.85	3	3
AP-1/NFAT1-c-4	-0.12	0.34	-9999	-1.2	3	3
FASLG	-0.09	0.25	-9999	-0.92	2	2
NFAT1-c-4/ICER1	-0.047	0.19	-9999	-0.83	2	2
IL2RA	-0.095	0.26	-9999	-0.87	3	3
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	0.002	0.29	-9999	-0.93	2	2
JunB/Fra1/NFAT1-c-4	-0.041	0.18	-9999	-0.8	2	2
IL4	0.002	0.29	-9999	-0.86	3	3
IL2	-0.001	0.016	-9999	-10000	0	0
IL3	-0.007	0.021	-9999	-10000	0	0
FKBP1A	0	0	-9999	-10000	0	0
BATF3	0	0	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0	0	-9999	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.05	0.21	-9999	-0.9	2	2
NF kappa B1 p50/RelA/I kappa B alpha	-0.013	0.041	-9999	-10000	0	0
AP1	-0.12	0.29	-9999	-0.84	5	5
mol:PIP3	-0.086	0.23	-9999	-0.74	4	4
AKT1	-0.033	0.14	-9999	-0.59	2	2
PTK2B	0.003	0.087	-9999	-0.35	2	2
RHOA	0.016	0.053	-9999	-10000	0	0
PIK3CB	0	0	-9999	-10000	0	0
mol:Ca2+	0.019	0.047	-9999	-10000	0	0
MAGI3	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
apoptosis	-0.04	0.15	-9999	-0.64	2	2
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.014	0.079	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.032	0.16	-9999	-0.72	1	1
endothelial cell migration	-0.032	0.22	-9999	-0.94	2	2
ADCY4	-0.19	0.31	-9999	-1.1	2	2
ADCY5	-0.19	0.31	-9999	-1.1	2	2
ADCY6	-0.19	0.31	-9999	-1.1	2	2
ADCY7	-0.19	0.31	-9999	-1.1	2	2
ADCY1	-0.23	0.34	-9999	-1.1	3	3
ADCY2	-0.19	0.31	-9999	-1.2	2	2
ADCY3	-0.19	0.31	-9999	-1.1	2	2
ADCY8	-0.19	0.31	-9999	-1.1	2	2
ADCY9	-0.19	0.31	-9999	-1.1	2	2
GSK3B	0.011	0.083	-9999	-10000	0	0
arachidonic acid secretion	-0.21	0.32	-9999	-0.76	4	4
GNG2	0	0	-9999	-10000	0	0
TRIP6	-0.005	0.01	-9999	-10000	0	0
GNAO1	-0.45	0.54	-9999	-1	16	16
HRAS	0	0	-9999	-10000	0	0
NFKBIA	0.024	0.067	-9999	-10000	0	0
GAB1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.03	0.18	-9999	-1.1	1	1
JUN	0	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.014	0.032	-9999	-10000	0	0
TIAM1	-0.039	0.24	-9999	-1.4	1	1
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	0.019	0.047	-9999	-10000	0	0
PLCB3	-0.011	0.025	-9999	-10000	0	0
FOS	-0.11	0.36	-9999	-1.3	3	3
positive regulation of mitosis	-0.21	0.32	-9999	-0.76	4	4
LPA/LPA1-2-3	-0.069	0.22	-9999	-0.96	2	2
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
stress fiber formation	-0.002	0.13	-9999	-0.51	2	2
GNAZ	-0.05	0.24	-9999	-1	2	2
EGFR/PI3K-beta/Gab1	-0.092	0.25	-9999	-0.79	4	4
positive regulation of dendritic cell cytokine production	-0.068	0.21	-9999	-0.94	2	2
LPA/LPA2/MAGI-3	-0.014	0.032	-9999	-10000	0	0
ARHGEF1	-0.046	0.2	-9999	-0.85	2	2
GNAI2	-0.033	0.23	-9999	-0.97	2	2
GNAI3	-0.033	0.23	-9999	-0.97	2	2
GNAI1	-0.033	0.23	-9999	-0.97	2	2
LPA/LPA3	-0.013	0.038	-9999	-10000	0	0
LPA/LPA2	-0.02	0.044	-9999	-10000	0	0
LPA/LPA1	-0.06	0.25	-9999	-1.1	2	2
HB-EGF/EGFR	-0.064	0.23	-9999	-1	2	2
HBEGF	0.007	0.043	-9999	-10000	0	0
mol:DAG	0.019	0.047	-9999	-10000	0	0
cAMP biosynthetic process	-0.3	0.41	-9999	-0.72	16	16
NFKB1	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
LYN	0.024	0.067	-9999	-10000	0	0
GNAQ	-0.013	0.021	-9999	-10000	0	0
LPAR2	-0.032	0.072	-9999	-10000	0	0
LPAR3	-0.021	0.061	-9999	-10000	0	0
LPAR1	-0.072	0.3	-9999	-1.3	2	2
IL8	-0.045	0.19	-9999	-0.52	3	3
PTK2	-0.062	0.2	-9999	-0.9	2	2
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.04	0.15	-9999	-0.65	2	2
EGFR	-0.073	0.3	-9999	-1.3	2	2
PLCG1	-0.018	0.04	-9999	-10000	0	0
PLD2	-0.062	0.2	-9999	-0.9	2	2
G12/G13	-0.05	0.21	-9999	-0.91	2	2
PI3K-beta	-0.04	0.16	-9999	-0.71	2	2
cell migration	-0.016	0.074	-9999	-10000	0	0
SLC9A3R2	0	0	-9999	-10000	0	0
PXN	-0.003	0.13	-9999	-0.52	2	2
HRAS/GTP	-0.24	0.31	-9999	-1.1	2	2
RAC1	0	0	-9999	-10000	0	0
MMP9	-0.021	0.061	-9999	-10000	0	0
PRKCE	0	0	-9999	-10000	0	0
PRKCD	0.026	0.045	-9999	-10000	0	0
Gi(beta/gamma)	-0.21	0.29	-9999	-1.1	2	2
mol:LPA	0	0.001	-9999	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.038	0.18	-9999	-0.76	2	2
MAPKKK cascade	-0.21	0.32	-9999	-0.76	4	4
contractile ring contraction involved in cytokinesis	0.016	0.053	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.049	0.15	-9999	-0.66	2	2
GNA15	-0.013	0.021	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
MAPT	0.014	0.081	-9999	-10000	0	0
GNA11	-0.013	0.021	-9999	-10000	0	0
Rac1/GTP	-0.034	0.2	-9999	-1.2	1	1
MMP2	-0.032	0.22	-9999	-0.95	2	2

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.21	0.23	-9999	-1	1	1
NCK1/PAK1/Dok-R	-0.012	0.072	-9999	-0.44	1	1
NCK1/Dok-R	-0.035	0.21	-9999	-1.3	1	1
PIK3CA	0	0.002	-9999	-10000	0	0
mol:beta2-estradiol	-0.012	0.007	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
SHC1	0.011	0.006	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
F2	-1	0.54	-9999	-1.3	28	28
TNIP2	0	0	-9999	-10000	0	0
NF kappa B/RelA	-0.032	0.19	-9999	-1.2	1	1
FN1	-0.036	0.22	-9999	-1.3	1	1
PLD2	0.17	0.26	-9999	-1.3	1	1
PTPN11	0	0	-9999	-10000	0	0
GRB14	-0.11	0.36	-9999	-1.3	3	3
ELK1	0.17	0.24	-9999	-1.2	1	1
GRB7	-0.036	0.22	-9999	-1.3	1	1
PAK1	0	0	-9999	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.055	0.23	-9999	-1.2	1	1
CDKN1A	0.2	0.2	-9999	-0.66	1	1
ITGA5	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
RasGAP/Dok-R	-0.035	0.21	-9999	-1.3	1	1
CRK	0	0	-9999	-10000	0	0
mol:NO	0.21	0.18	-9999	-0.71	1	1
PLG	-0.29	0.49	-9999	-1.8	1	1
mol:GDP	0	0	-9999	-10000	0	0
chemokinesis	0.062	0.2	-9999	-0.94	1	1
GRB2	0	0	-9999	-10000	0	0
PIK3R1	0.011	0.006	-9999	-10000	0	0
ANGPT2	0.12	0.22	-9999	-10000	0	0
BMX	0.17	0.26	-9999	-1.3	1	1
ANGPT1	0.24	0.11	-9999	-10000	0	0
tube development	0.2	0.21	-9999	-0.76	1	1
ANGPT4	0.004	0.006	-9999	-10000	0	0
response to hypoxia	-0.001	0.012	-9999	-10000	0	0
Tie2/Ang1/GRB14	-0.091	0.3	-9999	-1.1	2	2
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
FGF2	-0.036	0.22	-9999	-1.3	1	1
STAT5A (dimer)	0.2	0.22	-9999	-0.88	1	1
mol:L-citrulline	0.21	0.18	-9999	-0.71	1	1
AGTR1	-0.54	0.64	-9999	-1.3	15	15
MAPK14	0.17	0.27	-9999	-1.3	1	1
Tie2/SHP2	-0.039	0.23	-9999	-1.4	1	1
TEK	-0.043	0.26	-9999	-1.6	1	1
RPS6KB1	0.2	0.22	-9999	-0.95	1	1
Angiotensin II/AT1	-0.45	0.54	-9999	-1.1	15	15
Tie2/Ang1/GRB2	-0.031	0.23	-9999	-1.4	1	1
MAPK3	0.17	0.24	-9999	-1.2	1	1
MAPK1	0.17	0.24	-9999	-1.2	1	1
Tie2/Ang1/GRB7	-0.054	0.26	-9999	-1.1	2	2
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0.14	0.3	-9999	-1.3	1	1
PI3K	0.2	0.25	-9999	-1.2	1	1
FES	0.17	0.26	-9999	-1.3	1	1
Crk/Dok-R	-0.035	0.21	-9999	-1.3	1	1
Tie2/Ang1/ABIN2	-0.031	0.23	-9999	-1.4	1	1
blood circulation	0	0	-9999	-10000	0	0
negative regulation of caspase activity	0.21	0.21	-9999	-0.88	1	1
STAT5A	0	0	-9999	-10000	0	0
mol:ROS	0	0	-9999	-10000	0	0
PTK2	0.2	0.22	-9999	-0.95	1	1
Tie2/Ang2	0.19	0.26	-9999	-1.1	1	1
Tie2/Ang1	0.17	0.28	-9999	-1.5	1	1
FOXO1	0.23	0.21	-9999	-0.88	1	1
ELF1	0.022	0.019	-9999	-10000	0	0
ELF2	0.17	0.27	-9999	-1.4	1	1
mol:Choline	0.17	0.25	-9999	-1.2	1	1
cell migration	-0.013	0.052	-9999	-10000	0	0
FYN	0.2	0.23	-9999	-0.88	1	1
DOK2	0	0	-9999	-10000	0	0
negative regulation of cell cycle	0.19	0.18	-9999	-0.6	1	1
ETS1	0.02	0.003	-9999	-10000	0	0
PXN	0.2	0.19	-9999	-0.76	1	1
ITGB1	0	0	-9999	-10000	0	0
NOS3	0.22	0.2	-9999	-0.82	1	1
RAC1	0	0	-9999	-10000	0	0
TNF	0.017	0.033	-9999	-10000	0	0
MAPKKK cascade	0.17	0.25	-9999	-1.2	1	1
RASA1	0	0	-9999	-10000	0	0
Tie2/Ang1/Shc	0.14	0.27	-9999	-1.4	1	1
NCK1	0	0	-9999	-10000	0	0
vasculogenesis	0.21	0.17	-9999	-0.63	1	1
mol:Phosphatidic acid	0.17	0.25	-9999	-1.2	1	1
mol:Angiotensin II	0.001	0.001	-9999	-10000	0	0
mol:NADP	0.21	0.18	-9999	-0.71	1	1
Rac1/GTP	-0.024	0.14	-9999	-0.88	1	1
MMP2	0.17	0.26	-9999	-1.3	1	1

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.1	0.16	-10000	0	-0.45	1	1
NT3 (dimer)/TRKC	-0.3	0.49	-10000	0	-1.1	10	10
NT3 (dimer)/TRKB	-0.5	0.67	-10000	0	-1.3	14	14
SHC/Grb2/SOS1/GAB1/PI3K	0	0	-10000	0	-10000	0	0
RAPGEF1	0	0	-10000	0	-10000	0	0
BDNF	-0.021	0.061	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
DYNLT1	0	0	-10000	0	-10000	0	0
NTRK1	0	0	-10000	0	-10000	0	0
NTRK2	0	0	-10000	0	-10000	0	0
NTRK3	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)/TRKB	-0.25	0.42	-10000	0	-0.98	9	9
neuron apoptosis	0.093	0.17	0.51	1	-10000	0	1
SHC 2-3/Grb2	-0.1	0.18	-10000	0	-0.56	1	1
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.097	0.17	-10000	0	-0.52	1	1
SHC3	-0.097	0.18	-10000	0	-0.52	1	1
STAT3 (dimer)	0	0	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.5	0.67	-10000	0	-1.3	14	14
RIN/GDP	-0.036	0.13	-10000	0	-10000	0	0
GIPC1	0	0	-10000	0	-10000	0	0
KRAS	0	0	-10000	0	-10000	0	0
DNAJA3	-0.17	0.3	-10000	0	-0.67	9	9
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.029	0	-10000	0	-10000	0	0
MAGED1	0	0	-10000	0	-10000	0	0
PTPN11	0	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.011	0.044	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.027	0.16	-10000	0	-0.98	1	1
TRKA/NEDD4-2	0	0	-10000	0	-10000	0	0
ELMO1	0	0	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0	0	-10000	0	-10000	0	0
NGF	-0.036	0.22	-10000	0	-1.3	1	1
HRAS	0	0	-10000	0	-10000	0	0
DOCK1	0	0	-10000	0	-10000	0	0
GAB2	0	0	-10000	0	-10000	0	0
RIT2	0	0	-10000	0	-10000	0	0
RIT1	0	0	-10000	0	-10000	0	0
FRS2	0	0	-10000	0	-10000	0	0
DNM1	-0.032	0.072	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.16	0.29	-10000	0	-0.65	9	9
mol:GDP	-0.061	0.2	-10000	0	-0.45	5	5
NGF (dimer)	-0.036	0.21	-10000	0	-1.3	1	1
RhoG/GDP	0	0	-10000	0	-10000	0	0
RIT1/GDP	-0.032	0.13	-10000	0	-10000	0	0
TIAM1	-0.036	0.22	-10000	0	-1.3	1	1
PIK3R1	0	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.009	0.025	-10000	0	-10000	0	0
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0	0	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.36	0.58	-10000	0	-1.3	10	10
RAP1/GDP	-0.057	0.089	-10000	0	-10000	0	0
KIDINS220/CRKL	0	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.021	0.06	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.027	0.16	-10000	0	-0.97	1	1
Schwann cell development	-0.037	0.045	-10000	0	-10000	0	0
EHD4	0	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0	0	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.21	0.35	-10000	0	-0.77	10	10
ABL1	0	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	0.002	0.005	-10000	0	-10000	0	0
STAT3	0	0	-10000	0	-10000	0	0
axon guidance	-0.2	0.32	-10000	0	-0.72	10	10
MAPK3	-0.025	0.15	-10000	0	-0.91	1	1
MAPK1	-0.025	0.15	-10000	0	-0.91	1	1
CDC42/GDP	-0.032	0.13	-10000	0	-10000	0	0
NTF3	-0.36	0.58	-10000	0	-1.3	10	10
NTF4	-0.011	0.044	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	-0.027	0.16	-10000	0	-0.98	1	1
PI3K	0	0	-10000	0	-10000	0	0
FRS3	0	0	-10000	0	-10000	0	0
FAIM	0	0	-10000	0	-10000	0	0
GAB1	0	0	-10000	0	-10000	0	0
RASGRF1	-0.18	0.3	-10000	0	-0.69	9	9
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.27	0.44	-10000	0	-0.98	10	10
RGS19	0	0	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.096	-10000	0	-10000	0	0
Rac1/GDP	-0.032	0.13	-10000	0	-10000	0	0
NGF (dimer)/TRKA/GRIT	-0.027	0.16	-10000	0	-0.99	1	1
neuron projection morphogenesis	-0.12	0.28	-10000	0	-0.59	9	9
NGF (dimer)/TRKA/NEDD4-2	-0.027	0.16	-10000	0	-0.98	1	1
MAP2K1	0	0	-10000	0	-10000	0	0
NGFR	-0.33	0.57	-10000	0	-1.3	9	9
NGF (dimer)/TRKA/GIPC/GAIP	-0.014	0.077	-10000	0	-0.47	1	1
RAS family/GTP/PI3K	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0	0	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.038	0.14	-10000	0	-0.85	1	1
RASA1	0	0	-10000	0	-10000	0	0
TRKA/c-Abl	0	0	-10000	0	-10000	0	0
SQSTM1	0	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.007	0.02	-10000	0	-10000	0	0
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.024	0.14	-10000	0	-0.87	1	1
MATK	0	0	-10000	0	-10000	0	0
NEDD4L	0	0	-10000	0	-10000	0	0
RAS family/GDP	-0.054	0.086	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.18	0.32	-10000	0	-0.72	9	9
Rac1/GTP	-0.13	0.17	-10000	0	-0.44	5	5
FRS2 family/SHP2/CRK family	0	0	-10000	0	-10000	0	0

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.19	0.31	-9999	-0.93	1	1
PLK1	-0.042	0.079	-9999	-10000	0	0
BIRC5	-0.051	0.08	-9999	-10000	0	0
HSPA1B	-0.19	0.31	-9999	-0.93	1	1
MAP2K1	0.007	0.022	-9999	-10000	0	0
BRCA2	-0.19	0.31	-9999	-0.93	1	1
FOXM1	-0.22	0.35	-9999	-0.96	2	2
XRCC1	-0.19	0.31	-9999	-0.93	1	1
FOXM1B/p19	-0.24	0.28	-9999	-0.99	1	1
Cyclin D1/CDK4	-0.19	0.33	-9999	-1.1	1	1
CDC2	-0.21	0.33	-9999	-0.99	1	1
TGFA	-0.18	0.32	-9999	-0.94	2	2
SKP2	-0.19	0.31	-9999	-0.93	1	1
CCNE1	-0.03	0.078	-9999	-10000	0	0
CKS1B	-0.19	0.31	-9999	-0.93	1	1
RB1	-0.1	0.11	-9999	-10000	0	0
FOXM1C/SP1	-0.24	0.28	-9999	-1	1	1
AURKB	-0.024	0.07	-9999	-10000	0	0
CENPF	-0.21	0.33	-9999	-0.98	1	1
CDK4	-0.001	0.038	-9999	-10000	0	0
MYC	-0.17	0.29	-9999	-0.82	1	1
CHEK2	0.007	0.022	-9999	-10000	0	0
ONECUT1	-0.2	0.35	-9999	-1.1	2	2
CDKN2A	-0.032	0.077	-9999	-10000	0	0
LAMA4	-0.19	0.31	-9999	-0.93	1	1
FOXM1B/HNF6	-0.22	0.39	-9999	-1.3	2	2
FOS	-0.26	0.46	-9999	-1.5	3	3
SP1	0	0	-9999	-10000	0	0
CDC25B	-0.19	0.31	-9999	-0.93	1	1
response to radiation	-0.01	0.025	-9999	-10000	0	0
CENPB	-0.19	0.31	-9999	-0.93	1	1
CENPA	-0.21	0.33	-9999	-0.98	1	1
NEK2	-0.23	0.32	-9999	-0.98	1	1
HIST1H2BA	-0.2	0.31	-9999	-0.94	1	1
CCNA2	-0.025	0.073	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.22	0.34	-9999	-1.1	1	1
CCNB2	-0.22	0.32	-9999	-0.98	1	1
CCNB1	-0.21	0.33	-9999	-1	1	1
ETV5	-0.19	0.31	-9999	-0.93	1	1
ESR1	-0.94	0.72	-9999	-1.4	25	25
CCND1	-0.19	0.34	-9999	-1	2	2
GSK3A	0.009	0.018	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.022	0.07	-9999	-10000	0	0
CDK2	0.004	0.007	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.013	0.029	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.25	0.25	-9999	-0.99	1	1
GAS1	-0.19	0.31	-9999	-0.93	1	1
MMP2	-0.19	0.31	-9999	-0.93	1	1
RB1/FOXM1C	-0.18	0.33	-9999	-0.96	2	2
CREBBP	0	0	-9999	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0	0	-9999	-10000	0	0
TRAF2/ASK1	0	0	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
MAP2K3	-0.03	0.075	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.039	0.068	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	-0.62	0.65	-9999	-1.3	17	17
TXN	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
GADD45A	0	0	-9999	-10000	0	0
GADD45B	0	0	-9999	-10000	0	0
MAP3K1	0	0	-9999	-10000	0	0
MAP3K6	0	0	-9999	-10000	0	0
MAP3K7	0	0	-9999	-10000	0	0
MAP3K4	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	0	0	-9999	-10000	0	0
TAK1/TAB family	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0	0	-9999	-10000	0	0
TRAF2	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.034	0.036	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.62	0.65	-9999	-1.3	17	17
CCM2	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.47	0.49	-9999	-0.99	17	17
MAPK11	0	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.44	0.46	-9999	-0.92	17	17
OSM/MEKK3	0	0	-9999	-10000	0	0
TAOK1	0	0	-9999	-10000	0	0
TAOK2	0	0	-9999	-10000	0	0
TAOK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0	0	-9999	-10000	0	0
MAP3K10	0	0	-9999	-10000	0	0
MAP3K3	0	0	-9999	-10000	0	0
TRX/ASK1	0	0	-9999	-10000	0	0
GADD45/MTK1/MTK1	-0.42	0.44	-9999	-0.88	17	17

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.021	0	-9999	-10000	0	0
ADCY5	0.021	0	-9999	-10000	0	0
ADCY6	0.021	0	-9999	-10000	0	0
ADCY7	0.021	0	-9999	-10000	0	0
ADCY1	-0.064	0.28	-9999	-0.99	3	3
ADCY2	0.013	0.026	-9999	-10000	0	0
ADCY3	0.021	0	-9999	-10000	0	0
ADCY8	0.008	0.03	-9999	-10000	0	0
PRKCE	0.011	0	-9999	-10000	0	0
ADCY9	0.021	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	0.021	0.043	-9999	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	0.014	0.1	-10000	0	-0.6	1	1
ACTA1	0	0.14	-10000	0	-0.86	1	1
NUMA1	0.014	0.1	-10000	0	-0.6	1	1
SPTAN1	0.005	0.14	-10000	0	-0.85	1	1
LIMK1	0.002	0.14	-10000	0	-0.85	1	1
BIRC3	-0.005	0.032	-10000	0	-10000	0	0
BIRC2	0	0	-10000	0	-10000	0	0
BAX	0	0	-10000	0	-10000	0	0
CASP10	0.003	0.16	-10000	0	-0.97	1	1
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.014	0.1	-10000	0	-0.6	1	1
DIABLO	0	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.005	0.14	-10000	0	-0.83	1	1
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
GSN	0.005	0.14	-10000	0	-0.85	1	1
MADD	0	0	-10000	0	-10000	0	0
TFAP2A	0.03	0.014	-10000	0	-10000	0	0
BID	0.014	0.065	-10000	0	-0.37	1	1
MAP3K1	0.01	0.04	-10000	0	-10000	0	0
TRADD	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.005	0.14	-10000	0	-0.85	1	1
CASP9	0	0	-10000	0	-10000	0	0
DNA repair	-0.005	0.029	-10000	0	-10000	0	0
neuron apoptosis	0.024	0.012	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.011	0.14	-10000	0	-0.82	1	1
APAF1	0	0	-10000	0	-10000	0	0
CASP6	0.031	0.054	-10000	0	-10000	0	0
TRAF2	0	0	-10000	0	-10000	0	0
ICAD/CAD	0.012	0.14	-10000	0	-0.82	1	1
CASP7	-0.011	0.016	-10000	0	-10000	0	0
KRT18	0.018	0.015	-10000	0	-10000	0	0
apoptosis	0.016	0.13	-10000	0	-0.73	1	1
DFFA	0.005	0.14	-10000	0	-0.85	1	1
DFFB	0.005	0.14	-10000	0	-0.85	1	1
PARP1	0.005	0.03	-10000	0	-10000	0	0
actin filament polymerization	-0.011	0.13	0.77	1	-10000	0	1
TNF	-0.005	0.032	-10000	0	-10000	0	0
CYCS	0.016	0.049	-10000	0	-0.28	1	1
SATB1	0.014	0.15	-10000	0	-0.82	1	1
SLK	0.005	0.14	-10000	0	-0.85	1	1
p15 BID/BAX	-0.009	0.054	-10000	0	-10000	0	0
CASP2	0.049	0.006	-10000	0	-10000	0	0
JNK cascade	-0.01	0.04	-10000	0	-10000	0	0
CASP3	-0.004	0.15	-10000	0	-0.91	1	1
LMNB2	0.046	0.018	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
CASP4	0	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.002	0.01	-10000	0	-10000	0	0
negative regulation of DNA binding	0.03	0.014	-10000	0	-10000	0	0
stress fiber formation	0.005	0.14	-10000	0	-0.83	1	1
GZMB	-0.008	0.18	-10000	0	-1.1	1	1
CASP1	0	0	-10000	0	-10000	0	0
LMNB1	0.046	0.018	-10000	0	-10000	0	0
APP	0.024	0.012	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.011	0	-10000	0	-10000	0	0
VIM	0.01	0.12	-10000	0	-0.7	1	1
LMNA	0.046	0.018	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.001	0.004	-10000	0	-10000	0	0
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	0.005	0.14	-10000	0	-0.85	1	1
APAF-1/Caspase 9	-0.002	0.017	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.015	0.1	-10000	0	-0.59	1	1
CFL2	0.01	0.14	-10000	0	-0.8	1	1
GAS2	-0.14	0.35	-10000	0	-0.86	7	7
positive regulation of apoptosis	0.049	0.017	-10000	0	-10000	0	0
PRF1	-0.036	0.22	-10000	0	-1.3	1	1

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	-0.001	0.006	-10000	0	-10000	0	0
HSPA8	0.002	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.7	0.47	-10000	0	-1	25	25
AKT1	0.014	0	-10000	0	-10000	0	0
GSC	0.021	0.033	-10000	0	-10000	0	0
NKX2-5	0	0	-10000	0	-10000	0	0
muscle cell differentiation	-0.002	0.013	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1	0.007	0.022	-10000	0	-10000	0	0
SMAD4	0.024	0.021	-10000	0	-10000	0	0
CBFB	0	0	-10000	0	-10000	0	0
SAP18	0.001	0.004	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.006	0.019	-10000	0	-10000	0	0
SMAD3/SMAD4/VDR	0.004	0.016	-10000	0	-10000	0	0
MYC	0	0	-10000	0	-10000	0	0
CDKN2B	0.047	0.017	-10000	0	-10000	0	0
AP1	-0.066	0.22	-10000	0	-0.81	3	3
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.001	0.009	-10000	0	-10000	0	0
SP3	0	0	-10000	0	-10000	0	0
CREB1	0	0	-10000	0	-10000	0	0
FOXH1	-0.01	0.042	-10000	0	-10000	0	0
SMAD3/SMAD4/GR	-0.002	0.014	-10000	0	-10000	0	0
GATA3	-0.005	0.03	-10000	0	-10000	0	0
SKI/SIN3/HDAC complex/NCoR1	0.006	0.02	-10000	0	-10000	0	0
MEF2C/TIF2	-0.048	0.19	-10000	0	-0.84	2	2
endothelial cell migration	0.14	0.49	1.8	3	-10000	0	3
MAX	0.005	0.018	-10000	0	-10000	0	0
RBBP7	0.001	0.004	-10000	0	-10000	0	0
RBBP4	0.001	0.004	-10000	0	-10000	0	0
RUNX2	0	0	-10000	0	-10000	0	0
RUNX3	0	0	-10000	0	-10000	0	0
RUNX1	0	0	-10000	0	-10000	0	0
CTBP1	0	0	-10000	0	-10000	0	0
NR3C1	0.005	0.018	-10000	0	-10000	0	0
VDR	-0.005	0.032	-10000	0	-10000	0	0
CDKN1A	0.075	0.025	-10000	0	-10000	0	0
KAT2B	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.004	0.018	-10000	0	-10000	0	0
DCP1A	0	0	-10000	0	-10000	0	0
SKI	0.001	0.004	-10000	0	-10000	0	0
SERPINE1	-0.15	0.51	-10000	0	-1.8	3	3
SMAD3/SMAD4/ATF2	-0.001	0.013	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.001	0.013	-10000	0	-10000	0	0
SAP30	0.001	0.004	-10000	0	-10000	0	0
Cbp/p300/PIAS3	-0.002	0.008	-10000	0	-10000	0	0
JUN	-0.008	0.23	-10000	0	-0.78	3	3
SMAD3/SMAD4/IRF7	-0.001	0.013	-10000	0	-10000	0	0
TFE3	-0.003	0.01	-10000	0	-10000	0	0
COL1A2	0.17	0.12	-10000	0	-10000	0	0
mesenchymal cell differentiation	0.001	0.013	-10000	0	-10000	0	0
DLX1	-0.005	0.032	-10000	0	-10000	0	0
TCF3	0	0	-10000	0	-10000	0	0
FOS	-0.091	0.36	-10000	0	-1.3	3	3
SMAD3/SMAD4/Max	-0.002	0.014	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0	0	-10000	0	-10000	0	0
ZBTB17	0	0	-10000	0	-10000	0	0
LAMC1	0.057	0.028	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	-0.001	0.013	-10000	0	-10000	0	0
IRF7	0	0	-10000	0	-10000	0	0
ESR1	-0.91	0.6	-10000	0	-1.3	25	25
HNF4A	-0.036	0.22	-10000	0	-1.3	1	1
MEF2C	-0.001	0.005	-10000	0	-10000	0	0
SMAD2-3/SMAD4	-0.001	0.011	-10000	0	-10000	0	0
Cbp/p300/Src-1	-0.001	0.002	-10000	0	-10000	0	0
IGHV3OR16-13	0	0.002	-10000	0	-10000	0	0
TGIF2/HDAC complex	0	0	-10000	0	-10000	0	0
CREBBP	0.001	0.003	-10000	0	-10000	0	0
SKIL	0	0	-10000	0	-10000	0	0
HDAC1	0.001	0.004	-10000	0	-10000	0	0
HDAC2	0.001	0.004	-10000	0	-10000	0	0
SNIP1	0.001	0.005	-10000	0	-10000	0	0
GCN5L2	-0.002	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0	0.013	-10000	0	-10000	0	0
MSG1/HSC70	-0.004	0.028	-10000	0	-10000	0	0
SMAD2	0.014	0.009	-10000	0	-10000	0	0
SMAD3	0.022	0.022	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.001	0.008	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.02	0.011	-10000	0	-10000	0	0
NCOR1	0.001	0.004	-10000	0	-10000	0	0
NCOA2	-0.073	0.3	-10000	0	-1.3	2	2
NCOA1	0	0	-10000	0	-10000	0	0
MYOD/E2A	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.048	0.046	-10000	0	-10000	0	0
IFNB1	0.041	0.026	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	0.003	0.011	-10000	0	-10000	0	0
CITED1	-0.01	0.044	-10000	0	-10000	0	0
SMAD2-3/SMAD4/ARC105	0	0.01	-10000	0	-10000	0	0
RBL1	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.044	0.035	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	0	0	-10000	0	-10000	0	0
SMAD7	-0.035	0.12	-10000	0	-10000	0	0
MYC/MIZ-1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.028	0.12	-10000	0	-10000	0	0
IL10	0.052	0.031	-10000	0	-10000	0	0
PIASy/HDAC complex	0.003	0.011	-10000	0	-10000	0	0
PIAS3	0	0	-10000	0	-10000	0	0
CDK2	0.001	0.003	-10000	0	-10000	0	0
IL5	0.045	0.031	-10000	0	-10000	0	0
CDK4	-0.005	0.032	-10000	0	-10000	0	0
PIAS4	0.003	0.011	-10000	0	-10000	0	0
ATF3	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1	0	0.01	-10000	0	-10000	0	0
FOXG1	-0.001	0	-10000	0	-10000	0	0
FOXO3	0.027	0	-10000	0	-10000	0	0
FOXO1	0.027	0	-10000	0	-10000	0	0
FOXO4	0.027	0	-10000	0	-10000	0	0
heart looping	-0.001	0.005	-10000	0	-10000	0	0
CEBPB	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.001	0.018	-10000	0	-10000	0	0
MYOD1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.029	0.16	-10000	0	-1	1	1
SMAD3/SMAD4/GATA3	0.002	0.018	-10000	0	-10000	0	0
SnoN/SIN3/HDAC complex/NCoR1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.001	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.002	0.01	-10000	0	-10000	0	0
MED15	0	0	-10000	0	-10000	0	0
SP1	0.021	0.005	-10000	0	-10000	0	0
SIN3B	0.001	0.004	-10000	0	-10000	0	0
SIN3A	0.001	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.004	0.018	-10000	0	-10000	0	0
ITGB5	0.067	0.031	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.005	0.016	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.47	0.5	-10000	0	-1	17	17
AR	-0.62	0.65	-10000	0	-1.3	17	17
negative regulation of cell growth	0.002	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.003	0.015	-10000	0	-10000	0	0
E2F5	0	0	-10000	0	-10000	0	0
E2F4	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.005	0.019	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	0.002	0.01	-10000	0	-10000	0	0
TFDP1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.065	0.22	-10000	0	-0.81	3	3
SMAD3/SMAD4/RUNX2	-0.001	0.013	-10000	0	-10000	0	0
TGIF2	0	0	-10000	0	-10000	0	0
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	0	0	-10000	0	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 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	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
SMAD4	0	-9999	-9999
SMAD2	0.014	-9999	-9999
SMAD3	0.042	-9999	-9999
SMAD3/SMAD4	0	-9999	-9999
SMAD4/Ubc9/PIASy	0	-9999	-9999
SMAD2/SMAD2/SMAD4	0	-9999	-9999
PPM1A	0	-9999	-9999
CALM1	0	-9999	-9999
SMAD2/SMAD4	0	-9999	-9999
MAP3K1	0	-9999	-9999
TRAP-1/SMAD4	0	-9999	-9999
MAPK3	0	-9999	-9999
MAPK1	0	-9999	-9999
NUP214	0	-9999	-9999
CTDSP1	0	-9999	-9999
CTDSP2	0	-9999	-9999
CTDSPL	0	-9999	-9999
KPNB1	0	-9999	-9999
TGFBRAP1	0	-9999	-9999
UBE2I	0	-9999	-9999
NUP153	0	-9999	-9999
KPNA2	0	-9999	-9999
PIAS4	0	-9999	-9999

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-9999
KIRREL	0	0	-9999	-9999
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0	0	-9999	-9999
PLCG1	0	0	-9999	-9999
ARRB2	0	0	-9999	-9999
WASL	0	0	-9999	-9999
Nephrin/NEPH1/podocin/CD2AP	0	0	-9999	-9999
ChemicalAbstracts:57-88-5	0	0	-9999	-9999
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0	0	-9999	-9999
FYN	0	0	-9999	-9999
mol:Ca2+	0	0	-9999	-9999
mol:DAG	0	0	-9999	-9999
NPHS2	0.002	0	-9999	-9999
mol:IP3	0	0	-9999	-9999
regulation of endocytosis	0	0	-9999	-9999
Nephrin/NEPH1/podocin/Cholesterol	0	0	-9999	-9999
establishment of cell polarity	0	0	-9999	-9999
Nephrin/NEPH1/podocin/NCK1-2	0	0	-9999	-9999
Nephrin/NEPH1/beta Arrestin2	0	0	-9999	-9999
NPHS1	0.002	0	-9999	-9999
Nephrin/NEPH1/podocin	0	0	-9999	-9999
TJP1	0	0	-9999	-9999
NCK1	0	0	-9999	-9999
NCK2	0	0	-9999	-9999
heterophilic cell adhesion	0	0	-9999	-9999
Nephrin/NEPH1/podocin/PLCgamma1	0	0	-9999	-9999
CD2AP	0	0	-9999	-9999
Nephrin/NEPH1/podocin/GRB2	0	0	-9999	-9999
GRB2	0	0	-9999	-9999
homophilic cell adhesion	0	0	-9999	-9999
TRPC6	-0.002	0.013	-9999	-9999
cytoskeleton organization	0	0	-9999	-9999
Nephrin/NEPH1	0	0	-9999	-9999
Nephrin/NEPH1/ZO-1	0	0	-9999	-9999

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
FBXW11	0	0	-9999	-9999
mol:GTP	0	0	-9999	-9999
NF kappa B1 p50/RelA/I kappa B alpha	0.084	0	-9999	-9999
ERC1	0	0	-9999	-9999
RIP2/NOD2	0	0	-9999	-9999
NFKBIA	0.048	0	-9999	-9999
BIRC2	0	0	-9999	-9999
IKBKB	0	0	-9999	-9999
RIPK2	0	0	-9999	-9999
IKBKG	0	0	-9999	-9999
IKK complex/A20	0.002	0.012	-9999	-9999
NEMO/A20/RIP2	0	0	-9999	-9999
XPO1	0	0	-9999	-9999
NEMO/ATM	0	0	-9999	-9999
tumor necrosis factor receptor activity	0	0	-9999	-9999
RAN	0	0	-9999	-9999
Exportin 1/RanGTP	0	0	-9999	-9999
IKK complex/ELKS	0	0	-9999	-9999
BCL10/MALT1/TRAF6	0	0	-9999	-9999
NOD2	0	0	-9999	-9999
NFKB1	0	0	-9999	-9999
RELA	0	0	-9999	-9999
MALT1	0	0	-9999	-9999
cIAP1/UbcH5C	0	0	-9999	-9999
ATM	0	0	-9999	-9999
TNF/TNFR1A	-0.003	0.019	-9999	-9999
TRAF6	0	0	-9999	-9999
PRKCA	0	0	-9999	-9999
CHUK	0	0	-9999	-9999
UBE2D3	0	0	-9999	-9999
TNF	-0.005	0.032	-9999	-9999
NF kappa B1 p50/RelA	0	0	-9999	-9999
BCL10	0	0	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0.048	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-9999
TNFRSF1A	0	0	-9999	-9999
IKK complex	0	0	-9999	-9999
CYLD	0	0	-9999	-9999
IKK complex/PKC alpha	0	0	-9999	-9999

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0	0	-9999	-10000	0	0
HDAC3	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC5	0	0	-9999	-10000	0	0
GATA2/HDAC5	-0.003	0.019	-9999	-10000	0	0
HDAC5/BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC9	-0.005	0.032	-9999	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-9999	-10000	0	0
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
GATA2	-0.005	0.032	-9999	-10000	0	0
HDAC4/RFXANK	0	0	-9999	-10000	0	0
BCOR	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0	0	-9999	-10000	0	0
HDAC5	0	0	-9999	-10000	0	0
GNB1/GNG2	0	0	-9999	-10000	0	0
Histones	0	0.002	-9999	-10000	0	0
ADRBK1	0	0	-9999	-10000	0	0
HDAC4	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0	0	-9999	-10000	0	0
HDAC6	0	0	-9999	-10000	0	0
HDAC5/RFXANK	0	0	-9999	-10000	0	0
CAMK4	0	0	-9999	-10000	0	0
Tubulin/HDAC6	0	0	-9999	-10000	0	0
SUMO1	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
GATA1	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
NR3C1	0	0	-9999	-10000	0	0
SUMO1/HDAC4	0	0	-9999	-10000	0	0
SRF	0	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	0	0	-9999	-10000	0	0
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	0	0	-9999	-10000	0	0
HDAC4/ER alpha	-0.75	0.5	-9999	-1.1	25	25
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0	0.002	-9999	-10000	0	0
cell motility	0	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	-0.91	0.6	-9999	-1.3	25	25
HDAC6/HDAC11	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
HDAC4/MEF2C	0	0	-9999	-10000	0	0
GNG2	0	0	-9999	-10000	0	0
NCOR2	0	0	-9999	-10000	0	0
TUBB2A	0	0	-9999	-10000	0	0
HDAC11	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
ANKRA2	0	0	-9999	-10000	0	0
RFXANK	0	0	-9999	-10000	0	0
nuclear import	0	0	-9999	-10000	0	0

×

BARD1 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	Mean.of.Down.Perturbations
BARD1/CSTF1	0	0	-9999	-9999
ATM	0	0	-9999	-9999
UBE2D3	0	0	-9999	-9999
PRKDC	0	0	-9999	-9999
ATR	0	0	-9999	-9999
UBE2L3	0	0	-9999	-9999
FANCD2	-0.001	0.006	-9999	-9999
protein ubiquitination	-0.008	0.018	-9999	-9999
XRCC5	0	0	-9999	-9999
XRCC6	0	0	-9999	-9999
M/R/N Complex	0	0	-9999	-9999
MRE11A	0	0	-9999	-9999
DNA-PK	0	0	-9999	-9999
FA complex/FANCD2/Ubiquitin	0.007	0.014	-9999	-9999
FANCF	0	0	-9999	-9999
BRCA1	0	0	-9999	-9999
CCNE1	-0.032	0.072	-9999	-9999
CDK2/Cyclin E1	-0.019	0.042	-9999	-9999
FANCG	0	0	-9999	-9999
BRCA1/BACH1/BARD1	0	0	-9999	-9999
FANCE	0	0	-9999	-9999
FANCC	0	0	-9999	-9999
NBN	0	0	-9999	-9999
FANCA	0	0	-9999	-9999
DNA repair	0.054	0.037	-9999	-9999
BRCA1/BARD1/ubiquitin	0	0	-9999	-9999
BARD1/DNA-PK	0	0	-9999	-9999
FANCL	0	0	-9999	-9999
mRNA polyadenylation	0	0	-9999	-9999
BRCA1/BARD1/CTIP/M/R/N Complex	0	0	-9999	-9999
BRCA1/BACH1/BARD1/TopBP1	0	0	-9999	-9999
BRCA1/BARD1/P53	0	0	-9999	-9999
BARD1/CSTF1/BRCA1	0	0	-9999	-9999
BRCA1/BACH1	0	0	-9999	-9999
BARD1	0	0	-9999	-9999
PCNA	0	0	-9999	-9999
BRCA1/BARD1/UbcH5C	0	0	-9999	-9999
BRCA1/BARD1/UbcH7	0	0	-9999	-9999
BRCA1/BARD1/RAD51/PCNA	-0.014	0.026	-9999	-9999
BARD1/DNA-PK/P53	0	0	-9999	-9999
BRCA1/BARD1/Ubiquitin	0	0	-9999	-9999
BRCA1/BARD1/CTIP	0	0	-9999	-9999
FA complex	0	0	-9999	-9999
BARD1/EWS	0	0	-9999	-9999
RBBP8	0.022	0	-9999	-9999
TP53	0	0	-9999	-9999
TOPBP1	0	0	-9999	-9999
G1/S transition of mitotic cell cycle	0	0	-9999	-9999
BRCA1/BARD1	0.008	0.019	-9999	-9999
CSTF1	0	0	-9999	-9999
BARD1/EWS-Fli1	0	0	-9999	-9999
CDK2	0	0	-9999	-9999
UniProt:Q9BZD1	0	0	-9999	-9999
RAD51	-0.043	0.08	-9999	-9999
RAD50	0	0	-9999	-9999
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0	0	-9999	-9999
EWSR1	0	0	-9999	-9999

×

Syndecan-1-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0	0	-9999	-10000	0	0
CCL5	-0.036	0.22	-9999	-1.3	1	1
SDCBP	0	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.015	0.083	-9999	-0.46	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.023	0.072	-9999	-10000	0	0
Syndecan-1/Syntenin	-0.023	0.072	-9999	-0.44	1	1
MAPK3	-0.015	0.064	-9999	-10000	0	0
HGF/MET	-0.18	0.4	-9999	-1.1	6	6
TGFB1/TGF beta receptor Type II	0	0	-9999	-10000	0	0
BSG	0	0	-9999	-10000	0	0
keratinocyte migration	-0.022	0.071	-9999	-10000	0	0
Syndecan-1/RANTES	-0.047	0.16	-9999	-0.88	1	1
Syndecan-1/CD147	-0.019	0.068	-9999	-10000	0	0
Syndecan-1/Syntenin/PIP2	-0.022	0.069	-9999	-0.42	1	1
LAMA5	0	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.021	0.068	-9999	-0.41	1	1
MMP7	-0.12	0.093	-9999	-10000	0	0
HGF	-0.22	0.49	-9999	-1.3	6	6
Syndecan-1/CASK	-0.015	0.079	-9999	-0.44	1	1
Syndecan-1/HGF/MET	-0.16	0.31	-9999	-0.83	6	6
regulation of cell adhesion	0.015	0.071	-9999	-10000	0	0
HPSE	0	0	-9999	-10000	0	0
positive regulation of cell migration	-0.015	0.083	-9999	-0.46	1	1
SDC1	-0.015	0.083	-9999	-0.47	1	1
Syndecan-1/Collagen	-0.015	0.083	-9999	-0.46	1	1
PPIB	0	0	-9999	-10000	0	0
MET	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
MMP9	-0.021	0.061	-9999	-10000	0	0
MAPK1	-0.015	0.064	-9999	-10000	0	0
homophilic cell adhesion	-0.015	0.082	-9999	-0.46	1	1
MMP1	-0.07	0.093	-9999	-10000	0	0

×

PLK2 and PLK4 events

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	Mean.of.Down.Perturbations
PLK2	0	0	-9999	-9999
PLK4	-0.005	0.032	-9999	-9999
regulation of centriole replication	0.019	0.022	-9999	-9999

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.002	0.011	-9999	-9999
RGS9BP	0	0	-9999	-9999
mol:GTP	0	0	-9999	-9999
GRK1	0	0	-9999	-9999
mol:Na +	0	0	-9999	-9999
mol:ADP	0.006	0.005	-9999	-9999
GNAT2	0	0	-9999	-9999
RGS9-1/Gbeta5/R9AP	-0.005	0.021	-9999	-9999
mol:GDP	0	0	-9999	-9999
PDE6H/GNAT2/GTP	0	0	-9999	-9999
GRK7	0	0	-9999	-9999
CNGB3	0	0	-9999	-9999
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-9999
mol:Ca2+	0	0	-9999	-9999
Cone PDE6	-0.004	0.015	-9999	-9999
Cone Metarhodopsin II	0	0	-9999	-9999
Na + (4 Units)	0	0	-9999	-9999
GNAT2/GDP	-0.004	0.015	-9999	-9999
GNB5	0	0	-9999	-9999
mol:GMP (4 units)	0	0	-9999	-9999
Cone Transducin	-0.002	0.012	-9999	-9999
SLC24A2	0	0	-9999	-9999
GNB3/GNGT2	-0.003	0.019	-9999	-9999
GNB3	-0.005	0.032	-9999	-9999
GNAT2/GTP	0	0	-9999	-9999
CNGA3	0	0	-9999	-9999
ARR3	0	0	-9999	-9999
absorption of light	0	0	-9999	-9999
cGMP/Cone CNG Channel	0	0	-9999	-9999
mol:Pi	-0.005	0.021	-9999	-9999
Cone CNG Channel	0	0	-9999	-9999
mol:all-trans-retinal	0	0	-9999	-9999
mol:K +	0	0	-9999	-9999
RGS9	-0.011	0.044	-9999	-9999
PDE6C	0	0	-9999	-9999
GNGT2	0	0	-9999	-9999
mol:cGMP (4 units)	0	0	-9999	-9999
PDE6H	0	0	-9999	-9999

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
chromatin modification	0	0	-9999	-9999
CLOCK	0	0	-9999	-9999
TIMELESS/CRY2	0	0	-9999	-9999
DEC1/BMAL1	0	0	-9999	-9999
ATR	0	0	-9999	-9999
NR1D1	0.043	0.004	-9999	-9999
ARNTL	0	0	-9999	-9999
TIMELESS	0.043	0.004	-9999	-9999
NPAS2	-0.005	0.031	-9999	-9999
CRY2	0	0	-9999	-9999
mol:CO	-0.014	0	-9999	-9999
CHEK1	0	0	-9999	-9999
mol:HEME	0.014	0	-9999	-9999
PER1	0	0	-9999	-9999
BMAL/CLOCK/NPAS2	-0.002	0.011	-9999	-9999
BMAL1/CLOCK	0.05	0.004	-9999	-9999
S phase of mitotic cell cycle	0	0	-9999	-9999
TIMELESS/CHEK1/ATR	0	0	-9999	-9999
mol:NADPH	0.014	0	-9999	-9999
PER1/TIMELESS	0	0	-9999	-9999
PER1-2 / CRY1-2	0	0	-9999	-9999
DEC1	0	0	-9999	-9999

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.022	0.015	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.002	0.009	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin/Src	-0.071	0.044	-9999	-10000	0	0
AP1	-0.074	0.26	-9999	-0.82	4	4
ILK	-0.03	0.019	-9999	-10000	0	0
bone resorption	-0.022	0.14	-9999	-0.83	1	1
PTK2B	0	0	-9999	-10000	0	0
PYK2/p130Cas	0.051	0.033	-9999	-10000	0	0
ITGAV	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.033	0.18	-9999	-1.1	1	1
alphaV/beta3 Integrin/Osteopontin	0.026	0.047	-9999	-10000	0	0
MAP3K1	-0.031	0.02	-9999	-10000	0	0
JUN	0	0	-9999	-10000	0	0
MAPK3	-0.004	0.042	-9999	-10000	0	0
MAPK1	-0.004	0.042	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	-0.029	0.16	-9999	-0.94	1	1
ITGB3	0	0	-9999	-10000	0	0
NFKBIA	0.011	0.04	-9999	-10000	0	0
FOS	-0.11	0.36	-9999	-1.3	3	3
CD44	-0.005	0.032	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
PLAU	0.009	0.056	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.011	0.016	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
alphaV beta3 Integrin	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.03	0.024	-9999	-10000	0	0
VAV3	-0.03	0.062	-9999	-10000	0	0
MAP3K14	-0.017	0.043	-9999	-10000	0	0
ROCK2	-0.036	0.22	-9999	-1.3	1	1
SPP1	-0.13	0.082	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.034	0.038	-9999	-10000	0	0
MMP2	-0.056	0.2	-9999	-10000	0	0

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
MAPKKK cascade	-0.027	0.049	-9999	-9999
EFNA5	-0.043	0.08	-9999	-9999
FYN	-0.021	0.04	-9999	-9999
neuron projection morphogenesis	-0.027	0.049	-9999	-9999
cell-cell signaling	0	0	-9999	-9999
Ephrin A5/EPHA5	-0.027	0.049	-9999	-9999
EPHA5	-0.011	0.044	-9999	-9999

×

JNK signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.009	0.043	-9999	-10000	0	0
MAP4K1	-0.005	0.032	-9999	-10000	0	0
MAP3K8	0	0	-9999	-10000	0	0
PRKCB	-0.042	0.22	-9999	-1.3	1	1
DBNL	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
MAP3K1	-0.001	0.01	-9999	-10000	0	0
JUN	0.001	0.15	-9999	-0.62	2	2
MAP3K7	-0.001	0.01	-9999	-10000	0	0
GRAP2	-0.005	0.032	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
MAP2K4	0.051	0.017	-9999	-10000	0	0
LAT	-0.011	0.044	-9999	-10000	0	0
LCP2	0	0	-9999	-10000	0	0
MAPK8	-0.008	0.16	-9999	-0.66	2	2
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.002	0.012	-9999	-10000	0	0
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.005	0.039	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.036	0.22	-9999	-1.3	1	1
ITGA4	0	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.03	0.18	-9999	-1.1	1	1
alpha4/beta1 Integrin	0	0	-9999	-10000	0	0

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0	0	-9999	-10000	0	0
ANTXR2	0	0	-9999	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0	-9999	-10000	0	0
monocyte activation	-0.015	0.13	-9999	-0.54	2	2
MAP2K2	0	0	-9999	-10000	0	0
MAP2K1	0	0	-9999	-10000	0	0
MAP2K7	0	0	-9999	-10000	0	0
MAP2K6	0	0	-9999	-10000	0	0
CYAA	0	0	-9999	-10000	0	0
MAP2K4	0	0	-9999	-10000	0	0
IL1B	0.017	0.015	-9999	-10000	0	0
Channel	0	0	-9999	-10000	0	0
NLRP1	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
negative regulation of phagocytosis	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
regulation of endothelial cell proliferation	0	0	-9999	-10000	0	0
MAPK3	0	0	-9999	-10000	0	0
MAPK1	0	0	-9999	-10000	0	0
PGR	0	0	-9999	-10000	0	0
PA/Cellular Receptors	0	0	-9999	-10000	0	0
apoptosis	0	0	-9999	-10000	0	0
LOC728358	0	0	-9999	-10000	0	0
Lethal toxin (unfolded)	0	0	-9999	-10000	0	0
macrophage activation	0.021	0	-9999	-10000	0	0
TNF	-0.005	0.032	-9999	-10000	0	0
VCAM1	-0.03	0.12	-9999	-0.54	2	2
platelet activation	0	0	-9999	-10000	0	0
MAPKKK cascade	-0.018	0	-9999	-10000	0	0
IL18	-0.001	0.037	-9999	-10000	0	0
negative regulation of macrophage activation	0	0	-9999	-10000	0	0
LEF	0	0	-9999	-10000	0	0
CASP1	0	0	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
necrosis	0	0	-9999	-10000	0	0
intracellular pH reduction	0	0	-9999	-10000	0	0
PAGA	0	0	-9999	-10000	0	0
Edema toxin (unfolded)	0	0	-9999	-10000	0	0
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-9999	-10000	0	0

×

Signaling events mediated by PTP1B

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0	0	-9999	-10000	0	0
Jak2/Leptin Receptor	-0.3	0.42	-9999	-0.87	12	12
PTP1B/AKT1	-0.005	0.024	-9999	-10000	0	0
FYN	0	0	-9999	-10000	0	0
p210 bcr-abl/PTP1B	0.023	0.039	-9999	-10000	0	0
EGFR	-0.073	0.3	-9999	-1.3	2	2
EGF/EGFR	-0.048	0.21	-9999	-0.92	2	2
CSF1	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
INSR	0	0	-9999	-10000	0	0
PTP1B/N-cadherin	-0.03	0.14	-9999	-0.86	1	1
Insulin Receptor/Insulin	-0.002	0.018	-9999	-10000	0	0
HCK	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
TYK2	0.03	0.037	-9999	-10000	0	0
EGF	-0.016	0.056	-9999	-10000	0	0
YES1	0	0	-9999	-10000	0	0
CAV1	0.024	0.072	-9999	-10000	0	0
TXN	0	0.003	-9999	-10000	0	0
PTP1B/IRS1/GRB2	-0.005	0.023	-9999	-10000	0	0
cell migration	-0.023	0.039	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
PRLR	-0.14	0.41	-9999	-1.3	4	4
ITGA2B	-0.021	0.06	-9999	-10000	0	0
CSF1R	0	0	-9999	-10000	0	0
Prolactin Receptor/Prolactin	-0.12	0.34	-9999	-1.1	4	4
FGR	0	0	-9999	-10000	0	0
PTP1B/p130 Cas	-0.006	0.025	-9999	-10000	0	0
Crk/p130 Cas	-0.005	0.023	-9999	-10000	0	0
DOK1	0.035	0.033	-9999	-10000	0	0
JAK2	-0.016	0.13	-9999	-0.4	3	3
Jak2/Leptin Receptor/Leptin	-0.2	0.26	-9999	-0.72	3	3
PIK3R1	0	0	-9999	-10000	0	0
PTPN1	0.023	0.039	-9999	-10000	0	0
LYN	0	0	-9999	-10000	0	0
CDH2	-0.036	0.22	-9999	-1.3	1	1
SRC	0.024	0.017	-9999	-10000	0	0
ITGB3	0	0	-9999	-10000	0	0
CAT1/PTP1B	0.053	0.037	-9999	-10000	0	0
CAPN1	0	0.002	-9999	-10000	0	0
CSK	0	0	-9999	-10000	0	0
PI3K	-0.001	0.014	-9999	-10000	0	0
mol:H2O2	-0.001	0.003	-9999	-10000	0	0
STAT3 (dimer)	-0.18	0.24	-9999	-0.67	3	3
negative regulation of transcription	-0.016	0.13	-9999	-0.39	3	3
FCGR2A	0	0	-9999	-10000	0	0
FER	0	0.003	-9999	-10000	0	0
alphaIIb/beta3 Integrin	-0.013	0.035	-9999	-10000	0	0
BLK	-0.005	0.032	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.002	0.013	-9999	-10000	0	0
RHOA	0	0.002	-9999	-10000	0	0
LEPR	-0.43	0.62	-9999	-1.3	12	12
BCAR1	0	0	-9999	-10000	0	0
p210 bcr-abl/Grb2	0	0	-9999	-10000	0	0
mol:NADPH	0	0.003	-9999	-10000	0	0
TRPV6	0.044	0.013	-9999	-10000	0	0
PRL	0	0.003	-9999	-10000	0	0
SOCS3	-0.028	0.31	-9999	-1.8	1	1
SPRY2	0.001	0.004	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.002	0.013	-9999	-10000	0	0
CSF1/CSF1R	-0.005	0.023	-9999	-10000	0	0
Ras protein signal transduction	0.009	0.013	-9999	-10000	0	0
IRS1	0	0	-9999	-10000	0	0
INS	-0.005	0.031	-9999	-10000	0	0
LEP	-0.001	0.002	-9999	-10000	0	0
STAT5B	0.01	0.072	-9999	-0.25	2	2
STAT5A	0.01	0.072	-9999	-0.25	2	2
GRB2	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.006	0.025	-9999	-10000	0	0
CSN2	-0.032	0.081	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
LAT	0.024	0.016	-9999	-10000	0	0
YBX1	0	0	-9999	-10000	0	0
LCK	-0.005	0.032	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
NOX4	-0.021	0.06	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0.002	-9999	-10000	0	0
HDAC2	0	0.002	-9999	-10000	0	0
GNB1/GNG2	-0.027	0.16	-9999	-0.98	1	1
forebrain development	-0.019	0.099	-9999	-10000	0	0
GNAO1	-0.54	0.64	-9999	-1.3	15	15
SMO/beta Arrestin2	-0.03	0.18	-9999	-1.1	1	1
SMO	-0.03	0.22	-9999	-1.3	1	1
ARRB2	0	0	-9999	-10000	0	0
GLI3/SPOP	0.006	0.037	-9999	-10000	0	0
mol:GTP	0	0.001	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0	0	-9999	-10000	0	0
GNAI1	0	0	-9999	-10000	0	0
XPO1	0.014	0.002	-9999	-10000	0	0
GLI1/Su(fu)	-0.043	0.09	-9999	-0.51	1	1
SAP30	0	0.002	-9999	-10000	0	0
mol:GDP	-0.03	0.22	-9999	-1.3	1	1
MIM/GLI2A	0.016	0.017	-9999	-10000	0	0
IFT88	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GLI2	0.045	0.004	-9999	-10000	0	0
GLI3	0.047	0.033	-9999	-10000	0	0
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
SAP18	0	0.002	-9999	-10000	0	0
embryonic digit morphogenesis	0	0	-9999	-10000	0	0
GNG2	0	0	-9999	-10000	0	0
Gi family/GTP	-0.22	0.31	-9999	-0.54	15	15
SIN3B	0	0.002	-9999	-10000	0	0
SIN3A	0	0.002	-9999	-10000	0	0
GLI3/Su(fu)	0.001	0.005	-9999	-10000	0	0
GLI2/Su(fu)	-0.008	0.046	-9999	-10000	0	0
FOXA2	-0.041	0.26	-9999	-1.6	1	1
neural tube patterning	-0.019	0.099	-9999	-10000	0	0
SPOP	0	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.01	0.058	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
CSNK1G3	0	0	-9999	-10000	0	0
MTSS1	0.016	0.017	-9999	-10000	0	0
embryonic limb morphogenesis	-0.019	0.099	-9999	-10000	0	0
SUFU	-0.011	0.065	-9999	-0.4	1	1
LGALS3	-0.005	0.032	-9999	-10000	0	0
catabolic process	0	0	-9999	-10000	0	0
GLI3A/CBP	0	0	-9999	-10000	0	0
KIF3A	0	0	-9999	-10000	0	0
GLI1	-0.019	0.1	-9999	-10000	0	0
RAB23	0	0	-9999	-10000	0	0
CSNK1A1	0	0	-9999	-10000	0	0
IFT172	0	0	-9999	-10000	0	0
RBBP7	0	0.002	-9999	-10000	0	0
Su(fu)/Galectin3	-0.012	0.059	-9999	-10000	0	0
GNAZ	-0.032	0.072	-9999	-10000	0	0
RBBP4	0	0.002	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GLI2/SPOP	0	0	-9999	-10000	0	0
STK36	0.013	0.002	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.17	0.24	-9999	-1.2	1	1
PTCH1	-0.009	0.092	-9999	-10000	0	0
MIM/GLI1	-0.014	0.13	-9999	-0.6	1	1
CREBBP	0	0	-9999	-10000	0	0
Su(fu)/SIN3/HDAC complex	0	0.015	-9999	-10000	0	0

×

Presenilin action in Notch and Wnt 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0	0	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
AES	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
DTX1	-0.11	0.36	-9999	-1.3	3	3
LRP6/FZD1	0	0	-9999	-10000	0	0
TLE1	0	0	-9999	-10000	0	0
AP1	-0.043	0.14	-9999	-0.51	3	3
NCSTN	0	0	-9999	-10000	0	0
ADAM10	0	0	-9999	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.009	0.053	-9999	-10000	0	0
NICD/RBPSUH	0	0	-9999	-10000	0	0
WIF1	-0.048	0.083	-9999	-10000	0	0
NOTCH1	0	0	-9999	-10000	0	0
PSENEN	0	0	-9999	-10000	0	0
KREMEN2	-0.043	0.08	-9999	-10000	0	0
DKK1	-0.075	0.094	-9999	-10000	0	0
beta catenin/beta TrCP1	0	0	-9999	-10000	0	0
APH1B	0	0	-9999	-10000	0	0
APH1A	0	0	-9999	-10000	0	0
AXIN1	0.006	0.003	-9999	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	-0.013	0.08	-9999	-0.48	1	1
PSEN1	0	0	-9999	-10000	0	0
FOS	-0.11	0.36	-9999	-1.3	3	3
JUN	0	0	-9999	-10000	0	0
MAP3K7	0	0	-9999	-10000	0	0
CTNNB1	0.023	0.008	-9999	-10000	0	0
MAPK3	0	0	-9999	-10000	0	0
DKK2/LRP6/Kremen 2	-0.018	0.034	-9999	-10000	0	0
HNF1A	-0.036	0.22	-9999	-1.3	1	1
CTBP1	0	0	-9999	-10000	0	0
MYC	0.001	0.008	-9999	-10000	0	0
NKD1	-0.005	0.032	-9999	-10000	0	0
FZD1	0	0	-9999	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.072	0.24	-9999	-0.86	3	3
apoptosis	-0.043	0.14	-9999	-0.51	3	3
Delta 1/NOTCHprecursor	0	0	-9999	-10000	0	0
DLL1	0	0	-9999	-10000	0	0
PPARD	0.001	0.008	-9999	-10000	0	0
Gamma Secretase	0	0	-9999	-10000	0	0
APC	0.006	0.003	-9999	-10000	0	0
DVL1	0.003	0.005	-9999	-10000	0	0
CSNK2A1	0	0	-9999	-10000	0	0
MAP3K7IP1	-0.002	0	-9999	-10000	0	0
DKK1/LRP6/Kremen 2	-0.052	0.061	-9999	-10000	0	0
LRP6	0	0	-9999	-10000	0	0
CSNK1A1	0	0	-9999	-10000	0	0
NLK	0	0	-9999	-10000	0	0
CCND1	0.001	0.008	-9999	-10000	0	0
WNT1	0	0	-9999	-10000	0	0
Axin1/APC/beta catenin	0.044	0.006	-9999	-10000	0	0
DKK2	0	0	-9999	-10000	0	0
NOTCH1 precursor/DVL1	0	0	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
FRAT1	0	0	-9999	-10000	0	0
NOTCH/Deltex homolog 1	-0.072	0.24	-9999	-0.86	3	3
PPP2R5D	0.003	0.015	-9999	-10000	0	0
MAPK1	0	0	-9999	-10000	0	0
WNT1/LRP6/FZD1	-0.017	0.029	-9999	-10000	0	0
RBPJ	0	0	-9999	-10000	0	0
CREBBP	0.014	0	-9999	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
Aurora A/GADD45A	0	0	-9999	-9999
BIRC5	-0.1	0.096	-9999	-9999
NFKBIA	0.011	0.012	-9999	-9999
CPEB1	-0.037	0.076	-9999	-9999
AKT1	0.011	0.012	-9999	-9999
NDEL1	0	0	-9999	-9999
Aurora A/BRCA1	0	0	-9999	-9999
NDEL1/TACC3	-0.004	0.015	-9999	-9999
GADD45A	0	0	-9999	-9999
GSK3B	0	0	-9999	-9999
PAK1/Aurora A	0	0	-9999	-9999
MDM2	0	0	-9999	-9999
JUB	0	0	-9999	-9999
TPX2	0.019	0.022	-9999	-9999
TP53	0.011	0.012	-9999	-9999
DLG7	0.006	0.007	-9999	-9999
AURKAIP1	0	0	-9999	-9999
ARHGEF7	0	0	-9999	-9999
G2 phase of mitotic cell cycle	0	0	-9999	-9999
Aurora A/NDEL1/TACC3	-0.004	0.016	-9999	-9999
G2/M transition of mitotic cell cycle	0	0	-9999	-9999
AURKA	0.008	0.008	-9999	-9999
AURKB	0.006	0.009	-9999	-9999
CDC25B	0.011	0.012	-9999	-9999
G2/M transition checkpoint	0	0	-9999	-9999
mRNA polyadenylation	-0.014	0.031	-9999	-9999
Aurora A/CPEB	-0.014	0.031	-9999	-9999
Aurora A/TACC1/TRAP/chTOG	0	0	-9999	-9999
BRCA1	0	0	-9999	-9999
centrosome duplication	0	0	-9999	-9999
regulation of centrosome cycle	-0.004	0.014	-9999	-9999
spindle assembly	0	0	-9999	-9999
TDRD7	0	0	-9999	-9999
Aurora A/RasGAP/Survivin	-0.028	0.027	-9999	-9999
CENPA	0.01	0.011	-9999	-9999
Aurora A/PP2A	0	0	-9999	-9999
meiosis	0	0	-9999	-9999
protein catabolic process	0.033	0.002	-9999	-9999
negative regulation of DNA binding	0.011	0.012	-9999	-9999
prophase	0	0	-9999	-9999
GIT1/beta-PIX	0	0	-9999	-9999
RASA1	0	0	-9999	-9999
Ajuba/Aurora A	0	0	-9999	-9999
mitotic prometaphase	-0.004	0.006	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0.008	0.008	-9999	-9999
TACC1	0	0	-9999	-9999
TACC3	-0.011	0.044	-9999	-9999
Aurora A/Antizyme1	0	0	-9999	-9999
Aurora A/RasGAP	0	0	-9999	-9999
OAZ1	0	0	-9999	-9999
RAN	0	0	-9999	-9999
mitosis	0	0	-9999	-9999
PRKACA	0	0	-9999	-9999
GIT1	0	0	-9999	-9999
GIT1/beta-PIX/PAK1	0	0	-9999	-9999
Importin alpha/Importin beta/TPX2	0.019	0.022	-9999	-9999
PPP2R5D	0	0	-9999	-9999
Aurora A/TPX2	0.011	0.02	-9999	-9999
PAK1	0	0	-9999	-9999
CKAP5	0	0	-9999	-9999

×

Arf6 downstream pathway

Figure S70. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S70. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.037	0.025	-10000	0	-10000	0	0
regulation of axonogenesis	0	0	-10000	0	-10000	0	0
myoblast fusion	0.001	0.008	-10000	0	-10000	0	0
mol:GTP	-0.001	0.006	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.026	0.16	0.94	1	-10000	0	1
ARF1/GTP	0	0.002	-10000	0	-10000	0	0
mol:GM1	0.009	0.006	-10000	0	-10000	0	0
mol:Choline	0.028	0.007	-10000	0	-10000	0	0
lamellipodium assembly	0.003	0.026	-10000	0	-10000	0	0
MAPK3	0.026	0.012	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.027	0.16	-10000	0	-0.95	1	1
ARF1	0	0	-10000	0	-10000	0	0
ARF6/GDP	-0.001	0.008	-10000	0	-10000	0	0
ARF1/GDP	0.002	0.02	-10000	0	-10000	0	0
ARF6	0.009	0.002	-10000	0	-10000	0	0
RAB11A	0	0	-10000	0	-10000	0	0
TIAM1	-0.036	0.21	-10000	0	-1.3	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.026	0.012	-10000	0	-10000	0	0
actin filament bundle formation	0.001	0.005	-10000	0	-10000	0	0
KALRN	0.002	0.02	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.001	0.005	-10000	0	-10000	0	0
NME1	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.001	0.005	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.001	0.006	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.003	0.026	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
liver development	-0.001	0.006	-10000	0	-10000	0	0
ARF6/GTP	-0.001	0.006	-10000	0	-10000	0	0
RhoA/GTP	0	0.002	-10000	0	-10000	0	0
mol:GDP	0.003	0.024	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
PLD1	0.019	0.006	-10000	0	-10000	0	0
RAB11FIP3	0	0	-10000	0	-10000	0	0
tube morphogenesis	0.003	0.026	-10000	0	-10000	0	0
ruffle organization	0	0	-10000	0	-10000	0	0
regulation of epithelial cell migration	-0.001	0.006	-10000	0	-10000	0	0
PLD2	0.019	0.006	-10000	0	-10000	0	0
PIP5K1A	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.028	0.007	-10000	0	-10000	0	0
Rac1/GTP	0.003	0.026	-10000	0	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.046	0.15	-9999	-0.92	1	1
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.01	0.032	-9999	-10000	0	0
AURKB	-0.054	0.086	-9999	-10000	0	0
AURKC	-0.036	0.22	-9999	-1.3	1	1

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0	0	-9999	-10000	0	0
LAT2	-0.018	0.074	-9999	-10000	0	0
AP1	-0.072	0.18	-9999	-0.64	3	3
mol:PIP3	0.03	0.16	-9999	-0.6	2	2
IKBKB	0.035	0.096	-9999	-0.4	1	1
AKT1	-0.037	0.15	-9999	-10000	0	0
IKBKG	0.035	0.096	-9999	-0.4	1	1
MS4A2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
MAP3K1	0.049	0.07	-9999	-10000	0	0
mol:Ca2+	0.032	0.11	-9999	-0.43	2	2
LYN	0	0.001	-9999	-10000	0	0
CBLB	-0.017	0.072	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.026	0.15	-9999	-0.92	1	1
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.005	0.032	-9999	-10000	0	0
PLD2	-0.046	0.19	-9999	-0.83	2	2
PTPN13	0.022	0.079	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.053	0.11	-9999	-10000	0	0
SYK	-0.005	0.031	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.037	0.14	-9999	-0.62	2	2
LAT	-0.021	0.073	-9999	-10000	0	0
PAK2	0.043	0.075	-9999	-10000	0	0
NFATC2	-0.069	0.24	-9999	-1	2	2
HRAS	0.036	0.08	-9999	-10000	0	0
GAB2	0	0	-9999	-10000	0	0
PLA2G1B	0.024	0.016	-9999	-10000	0	0
Fc epsilon R1	-0.055	0.23	-9999	-0.99	2	2
Antigen/IgE/Fc epsilon R1	-0.052	0.21	-9999	-0.93	2	2
mol:GDP	0.029	0.08	-9999	-10000	0	0
JUN	0	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
FOS	-0.11	0.36	-9999	-1.3	3	3
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.019	0.078	-9999	-10000	0	0
CHUK	0.035	0.096	-9999	-0.4	1	1
KLRG1	-0.018	0.075	-9999	-10000	0	0
VAV1	-0.02	0.074	-9999	-10000	0	0
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.017	0.072	-9999	-10000	0	0
negative regulation of mast cell degranulation	-0.019	0.069	-9999	-10000	0	0
BTK	-0.017	0.069	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.04	0.13	-9999	-0.48	3	3
GAB2/PI3K/SHP2	-0.042	0.17	-9999	-0.75	2	2
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.022	0.087	-9999	-10000	0	0
RAF1	0.01	0.02	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.075	0.24	-9999	-0.88	3	3
FCER1G	0	0.001	-9999	-10000	0	0
FCER1A	-0.073	0.3	-9999	-1.3	2	2
Antigen/IgE/Fc epsilon R1/Fyn	-0.049	0.2	-9999	-0.88	2	2
MAPK3	0.022	0.016	-9999	-10000	0	0
MAPK1	0.022	0.016	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0.012	0.1	-9999	-0.57	1	1
DUSP1	-0.036	0.22	-9999	-1.3	1	1
NF-kappa-B/RelA	-0.011	0.046	-9999	-10000	0	0
actin cytoskeleton reorganization	0.021	0.08	-9999	-10000	0	0
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.017	0.062	-9999	-10000	0	0
FER	-0.017	0.072	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
ITK	-0.044	0.18	-9999	-0.75	2	2
SOS1	0	0	-9999	-10000	0	0
PLCG1	0.034	0.09	-9999	-10000	0	0
cytokine secretion	-0.008	0.033	-9999	-10000	0	0
SPHK1	-0.026	0.082	-9999	-10000	0	0
PTK2	0.021	0.082	-9999	-10000	0	0
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.037	0.15	-9999	-0.66	2	2
EDG1	0	0	-9999	-10000	0	0
mol:DAG	0.035	0.15	-9999	-0.58	2	2
MAP2K2	0.018	0.017	-9999	-10000	0	0
MAP2K1	0.018	0.017	-9999	-10000	0	0
MAP2K7	0	0	-9999	-10000	0	0
KLRG1/SHP2	-0.018	0.073	-9999	-10000	0	0
MAP2K4	0.02	0.005	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.077	0.26	-9999	-0.92	3	3
mol:Choline	-0.045	0.18	-9999	-0.81	2	2
SHC/Grb2/SOS1	-0.016	0.067	-9999	-10000	0	0
FYN	0	0	-9999	-10000	0	0
DOK1	0	0	-9999	-10000	0	0
PXN	0.028	0.078	-9999	-10000	0	0
HCLS1	-0.017	0.072	-9999	-10000	0	0
PRKCB	0.027	0.14	-9999	-0.53	2	2
FCGR2B	-0.036	0.22	-9999	-1.3	1	1
IGHE	0.002	0.003	-9999	-10000	0	0
KLRG1/SHIP	-0.019	0.07	-9999	-10000	0	0
LCP2	0	0	-9999	-10000	0	0
PLA2G4A	-0.019	0.072	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.045	0.18	-9999	-0.81	2	2
IKK complex	0.047	0.073	-9999	-10000	0	0
WIPF1	0	0	-9999	-10000	0	0

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.007	0.009	-9999	-10000	0	0
BUB1B	-0.009	0.027	-9999	-10000	0	0
PLK1	0.012	0.008	-9999	-10000	0	0
PLK1S1	0.012	0.005	-9999	-10000	0	0
KIF2A	0.02	0.008	-9999	-10000	0	0
regulation of mitotic centrosome separation	0.012	0.008	-9999	-10000	0	0
GOLGA2	0	0	-9999	-10000	0	0
Hec1/SPC24	-0.03	0.034	-9999	-10000	0	0
WEE1	0.016	0.009	-9999	-10000	0	0
cytokinesis	-0.006	0.057	-9999	-10000	0	0
PP2A-alpha B56	0.032	0.014	-9999	-10000	0	0
AURKA	0.012	0.005	-9999	-10000	0	0
PICH/PLK1	-0.011	0.032	-9999	-10000	0	0
CENPE	0.002	0.043	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.02	0.008	-9999	-10000	0	0
PPP2CA	0	0	-9999	-10000	0	0
FZR1	0	0	-9999	-10000	0	0
TPX2	0.012	0.006	-9999	-10000	0	0
PAK1	0	0	-9999	-10000	0	0
SPC24	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
CLSPN	0.01	0.008	-9999	-10000	0	0
GORASP1	0	0	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	0.007	0.005	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
STAG2	0	0	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.001	0.003	-9999	-10000	0	0
spindle elongation	0.012	0.008	-9999	-10000	0	0
ODF2	0	0	-9999	-10000	0	0
BUB1	0.024	0.011	-9999	-10000	0	0
TPT1	0.012	0.005	-9999	-10000	0	0
CDC25C	0.01	0.009	-9999	-10000	0	0
CDC25B	0	0	-9999	-10000	0	0
SGOL1	0.007	0.009	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.004	0.013	-9999	-10000	0	0
CDC14B	0.011	0	-9999	-10000	0	0
CDC20	-0.1	0.096	-9999	-10000	0	0
PLK1/PBIP1	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
FBXO5	0.017	0.008	-9999	-10000	0	0
CDC2	0.001	0.001	-9999	-10000	0	0
NDC80	-0.086	0.096	-9999	-10000	0	0
metaphase plate congression	0.011	0.006	-9999	-10000	0	0
ERCC6L	-0.009	0.029	-9999	-10000	0	0
NLP/gamma Tubulin	0.011	0.005	-9999	-10000	0	0
microtubule cytoskeleton organization	0.012	0.005	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	0	0	-9999	-10000	0	0
PPP1R12A	0	0	-9999	-10000	0	0
interphase	0	0	-9999	-10000	0	0
PLK1/PRC1-2	-0.053	0.067	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	0	0	-9999	-10000	0	0
RAB1A	0	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	0.019	0.005	-9999	-10000	0	0
mitotic prometaphase	-0.001	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.007	0.007	-9999	-10000	0	0
microtubule-based process	-0.034	0.041	-9999	-10000	0	0
Golgi organization	0.012	0.008	-9999	-10000	0	0
Cohesin/SA2	0	0	-9999	-10000	0	0
PPP1CB/MYPT1	0	0	-9999	-10000	0	0
KIF20A	-0.08	0.095	-9999	-10000	0	0
APC/C/CDC20	-0.043	0.041	-9999	-10000	0	0
PPP2R1A	0	0	-9999	-10000	0	0
chromosome segregation	0	0	-9999	-10000	0	0
PRC1	-0.054	0.086	-9999	-10000	0	0
ECT2	0.001	0.042	-9999	-10000	0	0
C13orf34	0.018	0.006	-9999	-10000	0	0
NUDC	0.011	0.006	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.009	0.027	-9999	-10000	0	0
spindle assembly	0.014	0.007	-9999	-10000	0	0
spindle stabilization	0.012	0.005	-9999	-10000	0	0
APC/C/HCDH1	0	0	-9999	-10000	0	0
MKLP2/PLK1	-0.034	0.041	-9999	-10000	0	0
CCNB1	-0.016	0.053	-9999	-10000	0	0
PPP1CB	0	0	-9999	-10000	0	0
BTRC	0	0	-9999	-10000	0	0
ROCK2	0.001	0.11	-9999	-0.65	1	1
TUBG1	0.012	0.005	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.004	0.013	-9999	-10000	0	0
MLF1IP	0.006	0.006	-9999	-10000	0	0
INCENP	0	0	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.018	0.072	-9999	-10000	0	0
CaM/Ca2+	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
AKT2	0	0	-9999	-10000	0	0
STXBP4	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	0.013	0.087	-9999	-0.35	2	2
YWHAZ	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
TBC1D4	0.022	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
SNARE/Synip	0	0	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
ASIP	0	0	-9999	-10000	0	0
PRKCI	0	0	-9999	-10000	0	0
AS160/CaM/Ca2+	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
GYS1	0	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
TRIP10	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
AS160/14-3-3	0.016	0.006	-9999	-10000	0	0
VAMP2	0	0	-9999	-10000	0	0
SLC2A4	0.012	0.096	-9999	-0.38	2	2
STX4	0	0	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
SFN	-0.17	0.061	-9999	-10000	0	0
LNPEP	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0

×

PDGFR-alpha 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.002	0.007	-9999	-10000	0	0
PDGF/PDGFRA/CRKL	0	0	-9999	-10000	0	0
positive regulation of JUN kinase activity	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	0	0.002	-9999	-10000	0	0
AP1	-0.13	0.43	-9999	-1.5	3	3
mol:IP3	0.021	0.019	-9999	-10000	0	0
PLCG1	0.021	0.019	-9999	-10000	0	0
PDGF/PDGFRA/alphaV Integrin	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
mol:Ca2+	0.021	0.019	-9999	-10000	0	0
CAV3	0	0	-9999	-10000	0	0
CAV1	0	0	-9999	-10000	0	0
SHC/Grb2/SOS1	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Shf	-0.03	0.18	-9999	-1.1	1	1
FOS	-0.078	0.42	-9999	-1.5	3	3
JUN	-0.005	0.018	-9999	-10000	0	0
oligodendrocyte development	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
mol:DAG	0.021	0.019	-9999	-10000	0	0
PDGF/PDGFRA	-0.002	0.007	-9999	-10000	0	0
actin cytoskeleton reorganization	0	0	-9999	-10000	0	0
SRF	0.004	0.013	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk/C3G	0	0	-9999	-10000	0	0
JAK1	0.022	0.007	-9999	-10000	0	0
ELK1/SRF	-0.001	0.004	-9999	-10000	0	0
SHB	0	0	-9999	-10000	0	0
SHF	-0.036	0.22	-9999	-1.3	1	1
CSNK2A1	0.005	0.016	-9999	-10000	0	0
GO:0007205	0.022	0.022	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
Ras protein signal transduction	0	0	-9999	-10000	0	0
PDGF/PDGFRA/SHB	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-1	0	0	-9999	-10000	0	0
ITGAV	0	0	-9999	-10000	0	0
ELK1	0.027	0.032	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	0	0	-9999	-10000	0	0
JAK-STAT cascade	0.022	0.007	-9999	-10000	0	0
cell proliferation	-0.03	0.18	-9999	-1.1	1	1

×

mTOR signaling pathway

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
GBL	0	0	-9999	-9999
MKNK1	0	0	-9999	-9999
mol:PIP3	0	0	-9999	-9999
FRAP1	0.015	0	-9999	-9999
AKT1	0	0	-9999	-9999
INSR	0	0	-9999	-9999
Insulin Receptor/Insulin	-0.003	0.015	-9999	-9999
mol:GTP	0	0	-9999	-9999
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0	-9999	-9999
TSC2	0	0	-9999	-9999
RHEB/GDP	0	0	-9999	-9999
TSC1	0	0	-9999	-9999
Insulin Receptor/IRS1	0	0	-9999	-9999
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0	-9999	-9999
mol:GDP	0	0	-9999	-9999
EIF3A	0	0	-9999	-9999
RPS6KB1	0.028	0	-9999	-9999
MAP3K5	0.01	0	-9999	-9999
PIK3R1	0	0	-9999	-9999
apoptosis	0.01	0	-9999	-9999
mol:LY294002	0	0	-9999	-9999
EIF4B	0.034	0	-9999	-9999
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0	0	-9999	-9999
eIF4E/eIF4G1/eIF4A1	0	0	-9999	-9999
KIAA1303	0	0	-9999	-9999
PI3K	0	0	-9999	-9999
mTOR/RHEB/GTP/Raptor/GBL	0.033	0	-9999	-9999
FKBP1A	0	0	-9999	-9999
RHEB/GTP	0	0	-9999	-9999
mol:Amino Acids	0	0	-9999	-9999
FKBP12/Rapamycin	0	0	-9999	-9999
PDPK1	0	0	-9999	-9999
EIF4E	0	0	-9999	-9999
ASK1/PP5C	0	0	-9999	-9999
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.016	0	-9999	-9999
TSC1/TSC2	0	0	-9999	-9999
tumor necrosis factor receptor activity	0	0	-9999	-9999
RPS6	0	0	-9999	-9999
PPP5C	0	0	-9999	-9999
EIF4G1	0	0	-9999	-9999
IRS1	0.008	0	-9999	-9999
INS	-0.005	0.032	-9999	-9999
PTEN	0	0	-9999	-9999
PDK2	0	0	-9999	-9999
EIF4EBP1	0.01	0	-9999	-9999
PIK3CA	0	0	-9999	-9999
PPP2R5D	0.022	0	-9999	-9999
peptide biosynthetic process	-0.002	0.012	-9999	-9999
RHEB	0	0	-9999	-9999
EIF4A1	0	0	-9999	-9999
mol:Rapamycin	0	0	-9999	-9999
EEF2	-0.002	0.012	-9999	-9999
eIF4E/4E-BP1	0	0	-9999	-9999

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	0	0	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.066	0.07	-9999	-10000	0	0
CaM/Ca2+	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
MAP2K1	0.057	0.003	-9999	-10000	0	0
MAP3K11	0	0	-9999	-10000	0	0
IFNGR1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.23	0.25	-9999	-10000	0	0
Rap1/GTP	0	0	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0	0	-9999	-10000	0	0
CEBPB	0.083	0.009	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.001	0.006	-9999	-10000	0	0
STAT1	0.002	0.01	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
IFN-gamma (dimer)	0.001	0.001	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	0	0	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
MAPK3	0.064	0.008	-9999	-10000	0	0
STAT1 (dimer)	-0.084	0.093	-9999	-10000	0	0
MAPK1	0.064	0.008	-9999	-10000	0	0
JAK2	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
JAK1	0	0	-9999	-10000	0	0
CAMK2D	0	0	-9999	-10000	0	0
DAPK1	0.077	0.007	-9999	-10000	0	0
SMAD7	0.003	0.069	-9999	-10000	0	0
CBL/CRKL/C3G	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
IFNG	0.001	0.001	-9999	-10000	0	0
apoptosis	0.05	0.018	-9999	-10000	0	0
CAMK2G	0	0	-9999	-10000	0	0
STAT3 (dimer)	0	0	-9999	-10000	0	0
CAMK2A	-0.011	0.044	-9999	-10000	0	0
CAMK2B	-0.62	0.65	-9999	-1.3	17	17
FRAP1	0.057	0.003	-9999	-10000	0	0
PRKCD	0	0	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
negative regulation of cell growth	-0.066	0.07	-9999	-10000	0	0
PTPN2	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
IRF1	0.081	0.008	-9999	-10000	0	0
STAT1 (dimer)/PIASy	0.002	0.013	-9999	-10000	0	0
SOCS1	-0.003	0.015	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CASP1	0.003	0.069	-9999	-10000	0	0
PTGES2	0	0	-9999	-10000	0	0
IRF9	0.062	0.004	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
RAP1/GDP	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
MAP3K1	0.047	0.003	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
PIAS4	0	0	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.066	0.07	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.022	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-9999	-10000	0	0
CDKN1B	0.037	0	-9999	-10000	0	0
CDKN1A	0.037	0	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0	0	-9999	-10000	0	0
FOXO3	0.037	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
BAD	0	0	-9999	-10000	0	0
AKT3	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.037	0	-9999	-10000	0	0
AKT1/ASK1	0	0	-9999	-10000	0	0
BAD/YWHAZ	0	0	-9999	-10000	0	0
RICTOR	0	0	-9999	-10000	0	0
RAF1	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
TSC1	0.037	0	-9999	-10000	0	0
YWHAZ	0	0	-9999	-10000	0	0
AKT1/RAF1	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.037	0	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
TBC1D4	0.025	0	-9999	-10000	0	0
MAP3K5	0	0	-9999	-10000	0	0
MAPKAP1	0	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.026	0.006	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0
AKT1S1	0.037	0	-9999	-10000	0	0
CASP9	0.037	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
p27Kip1/KPNA1	0	0	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
AKT2/p21CIP1	0	0	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.017	0	-9999	-10000	0	0
CHUK	0.037	0	-9999	-10000	0	0
BAD/BCL-XL	0	0	-9999	-10000	0	0
mTORC2	0	0	-9999	-10000	0	0
AKT2	0	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.041	0.006	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
MDM2	0.037	0	-9999	-10000	0	0
MAPKKK cascade	0	0	-9999	-10000	0	0
MDM2/Cbp/p300	0	0	-9999	-10000	0	0
TSC1/TSC2	0.044	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
glucose import	-0.021	0.21	-9999	-0.9	2	2
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.031	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	-0.021	0.22	-9999	-0.92	2	2
GSK3A	0.037	0	-9999	-10000	0	0
FOXO1	0.037	0	-9999	-10000	0	0
GSK3B	0.037	0	-9999	-10000	0	0
SFN	-0.17	0.061	-9999	-10000	0	0
G1/S transition of mitotic cell cycle	0.044	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.018	0.006	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
KPNA1	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
RHEB	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0	0	-9999	-10000	0	0
alphaV beta3 Integrin	0	0	-9999	-10000	0	0
PTK2	-0.02	0.12	-9999	-0.73	1	1
positive regulation of JNK cascade	-0.011	0.064	-9999	-0.39	1	1
CDC42/GDP	0.038	0.099	-9999	-0.54	1	1
Rac1/GDP	0.041	0.098	-9999	-0.54	1	1
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.014	0.081	-9999	-0.49	1	1
nectin-3/I-afadin	-0.03	0.18	-9999	-1.1	1	1
RAPGEF1	0.037	0.11	-9999	-0.64	1	1
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.028	0.13	-9999	-0.76	1	1
PDGFB-D/PDGFRB	0	0	-9999	-10000	0	0
TLN1	-0.009	0.055	-9999	-10000	0	0
Rap1/GTP	-0.012	0.07	-9999	-0.42	1	1
IQGAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.03	0.18	-9999	-1.1	1	1
PVR	0	0	-9999	-10000	0	0
Necl-5(dimer)	0	0	-9999	-10000	0	0
mol:GDP	0.037	0.12	-9999	-0.7	1	1
MLLT4	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
PI3K	-0.024	0.14	-9999	-0.87	1	1
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.003	0.019	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.011	0.067	-9999	-0.41	1	1
PVRL1	-0.005	0.032	-9999	-10000	0	0
PVRL3	-0.036	0.22	-9999	-1.3	1	1
PVRL2	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
CDH1	0	0	-9999	-10000	0	0
CLDN1	-0.036	0.22	-9999	-1.3	1	1
JAM-A/CLDN1	-0.048	0.28	-9999	-1.7	1	1
SRC	-0.024	0.14	-9999	-0.88	1	1
ITGB3	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin	-0.003	0.019	-9999	-10000	0	0
FARP2	0.031	0.12	-9999	-0.68	1	1
RAC1	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.027	0.16	-9999	-0.98	1	1
nectin-1/I-afadin	-0.003	0.019	-9999	-10000	0	0
nectin-2/I-afadin	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.029	0.16	-9999	-0.98	1	1
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.011	0.064	-9999	-0.39	1	1
alphaV/beta3 Integrin/Talin	-0.008	0.048	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	-0.01	0.059	-9999	-10000	0	0
VAV2	0.03	0.12	-9999	-0.7	1	1
RAP1/GDP	-0.014	0.082	-9999	-0.5	1	1
ITGAV	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.027	0.16	-9999	-0.98	1	1
nectin-3(dimer)/I-afadin/I-afadin	-0.03	0.18	-9999	-1.1	1	1
Rac1/GTP	-0.014	0.084	-9999	-0.51	1	1
PTPRM	-0.011	0.066	-9999	-0.4	1	1
E-cadherin/beta catenin/alpha catenin	0.001	0.008	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.011	0.037	-9999	-10000	0	0
MAP4K4	0.001	0.004	-9999	-10000	0	0
BAG4	0	0	-9999	-10000	0	0
PKC zeta/ceramide	-0.004	0.006	-9999	-10000	0	0
NFKBIA	0	0	-9999	-10000	0	0
BIRC3	-0.005	0.032	-9999	-10000	0	0
BAX	0.003	0.009	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
AKT1	0.019	0.006	-9999	-10000	0	0
BAD	0.002	0.018	-9999	-10000	0	0
SMPD1	0.03	0.007	-9999	-10000	0	0
RB1	0.002	0.018	-9999	-10000	0	0
FADD/Caspase 8	0.002	0.007	-9999	-10000	0	0
MAP2K4	0.009	0.017	-9999	-10000	0	0
NSMAF	0	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
RAF1	0.009	0.017	-9999	-10000	0	0
EGF	-0.016	0.053	-9999	-10000	0	0
mol:ceramide	-0.008	0.019	-9999	-10000	0	0
MADD	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
mol:Free Fatty acid	0.011	0.037	-9999	-10000	0	0
ASAH1	0	0	-9999	-10000	0	0
negative regulation of cell cycle	0.002	0.018	-9999	-10000	0	0
cell proliferation	-0.35	0.33	-9999	-0.66	19	19
BID	0.035	0.007	-9999	-10000	0	0
MAP3K1	0.002	0.018	-9999	-10000	0	0
EIF2A	0.017	0.016	-9999	-10000	0	0
TRADD	0	0	-9999	-10000	0	0
CRADD	0	0	-9999	-10000	0	0
MAPK3	0.021	0.016	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
MAPK1	0.021	0.016	-9999	-10000	0	0
Cathepsin D/ceramide	-0.004	0.006	-9999	-10000	0	0
FADD	0.001	0.004	-9999	-10000	0	0
KSR1	0.002	0.018	-9999	-10000	0	0
MAPK8	0.004	0.06	-9999	-0.34	1	1
PRKRA	0.002	0.018	-9999	-10000	0	0
PDGFA	-0.016	0.053	-9999	-10000	0	0
TRAF2	0	0	-9999	-10000	0	0
IGF1	-0.69	0.65	-9999	-1.3	19	19
mol:GD3	0	0	-9999	-10000	0	0
ganglioside biosynthetic process	-0.008	0.019	-9999	-10000	0	0
CTSD	0	0	-9999	-10000	0	0
regulation of nitric oxide biosynthetic process	0	0	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
ERK1/PKC delta	-0.39	0.37	-9999	-0.74	19	19
PRKCD	0	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
mol:GW4869	0	0	-9999	-10000	0	0
mol:sphingosine	0.011	0.037	-9999	-10000	0	0
RelA/NF kappa B1	0	0	-9999	-10000	0	0
mol:glutathione	0	0	-9999	-10000	0	0
PAWR	0	0	-9999	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.001	0.003	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.002	0.013	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.011	0.037	-9999	-10000	0	0
MAP2K1	0.017	0.016	-9999	-10000	0	0
mol:C11AG	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
CYCS	0.003	0.013	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
TNFR1A/BAG4	0	0	-9999	-10000	0	0
EIF2AK2	0.009	0.017	-9999	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.002	0.013	-9999	-10000	0	0
response to hydrogen peroxide	0	0	-9999	-10000	0	0
CASP8	0.001	0.005	-9999	-10000	0	0
MAP2K2	0.017	0.016	-9999	-10000	0	0
SMPD3	0.032	0.007	-9999	-10000	0	0
TNF	-0.005	0.032	-9999	-10000	0	0
PKC zeta/PAR4	0	0	-9999	-10000	0	0
mol:PHOSPHOCHOLINE	0	0.019	-9999	-10000	0	0
NF kappa B1/RelA/I kappa B alpha	0	0	-9999	-10000	0	0
AIFM1	0.003	0.013	-9999	-10000	0	0
BCL2	0	0	-9999	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0	0	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
MAP2K4	0	0	-9999	-10000	0	0
IKBKB	0	0	-9999	-10000	0	0
TNFRSF10B	0	0	-9999	-10000	0	0
TNFRSF10A	0	0	-9999	-10000	0	0
SMPD1	0	0	-9999	-10000	0	0
IKBKG	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0	0	-9999	-10000	0	0
TRAIL/TRAILR2	0	0	-9999	-10000	0	0
TRAIL/TRAILR3	-0.003	0.019	-9999	-10000	0	0
TRAIL/TRAILR1	0	0	-9999	-10000	0	0
TRAIL/TRAILR4	0	0	-9999	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP	0	0	-9999	-10000	0	0
IKK complex	0	0	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0	0	-9999	-10000	0	0
MAPK3	0.022	0	-9999	-10000	0	0
MAP3K1	0	0	-9999	-10000	0	0
TRAILR4 (trimer)	0	0	-9999	-10000	0	0
TRADD	0	0	-9999	-10000	0	0
TRAILR1 (trimer)	0	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0	0	-9999	-10000	0	0
CFLAR	0	0	-9999	-10000	0	0
MAPK1	0.022	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP	0	0	-9999	-10000	0	0
mol:ceramide	0	0	-9999	-10000	0	0
FADD	0	0	-9999	-10000	0	0
MAPK8	0.029	0.14	-9999	-0.82	1	1
TRAF2	0	0	-9999	-10000	0	0
TRAILR3 (trimer)	-0.005	0.032	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	0	0	-9999	-10000	0	0
DAP3	0	0	-9999	-10000	0	0
CASP10	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
TRAIL (trimer)	0	0	-9999	-10000	0	0
TNFRSF10C	-0.005	0.032	-9999	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP/FADD	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD	0	0	-9999	-10000	0	0
cell death	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0	0	-9999	-10000	0	0
TRAILR2 (trimer)	0	0	-9999	-10000	0	0
CASP8	0	0	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0	0	-9999	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.01	0.058	-9999	-10000	0	0
IRAK/TOLLIP	0	0	-9999	-10000	0	0
IKBKB	0	0	-9999	-10000	0	0
IKBKG	0	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.013	0.035	-9999	-10000	0	0
IL1A	-0.021	0.061	-9999	-10000	0	0
IL1B	0.019	0.022	-9999	-10000	0	0
IRAK/TRAF6/p62/Atypical PKCs	0	0	-9999	-10000	0	0
IL1R2	0	0	-9999	-10000	0	0
IL1R1	0	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.01	0.057	-9999	-10000	0	0
TOLLIP	0	0	-9999	-10000	0	0
TICAM2	0	0	-9999	-10000	0	0
MAP3K3	0	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0	0	-9999	-10000	0	0
JUN	0.023	0.12	-9999	-0.72	1	1
MAP3K7	0	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.024	0.14	-9999	-0.84	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.032	0.15	-9999	-0.92	1	1
PIK3R1	0	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.019	0.14	-9999	-0.87	1	1
IL1 beta fragment/IL1R1/IL1RAP	-0.027	0.15	-9999	-0.92	1	1
NFKB1	0	0	-9999	-10000	0	0
MAPK8	-0.022	0.13	-9999	-0.8	1	1
IRAK1	0	0	-9999	-10000	0	0
IL1RN/IL1R1	-0.33	0.5	-9999	-1.1	11	11
IRAK4	0	0	-9999	-10000	0	0
PRKCI	0	0	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.011	0.066	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.027	0.15	-9999	-0.92	1	1
IL1 beta/IL1R2	-0.002	0.013	-9999	-10000	0	0
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.021	0.12	-9999	-0.75	1	1
IRAK3	0	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.024	0.14	-9999	-0.84	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.014	0.077	-9999	-0.47	1	1
IL1 alpha/IL1R1/IL1RAP	-0.036	0.16	-9999	-0.98	1	1
RELA	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0	0	-9999	-10000	0	0
MYD88	0	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0	0	-9999	-10000	0	0
IL1RAP	-0.036	0.22	-9999	-1.3	1	1
UBE2N	0	0	-9999	-10000	0	0
IRAK/TRAF6	-0.019	0.11	-9999	-10000	0	0
CASP1	0	0	-9999	-10000	0	0
IL1RN/IL1R2	-0.33	0.5	-9999	-1.1	11	11
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.026	0.14	-9999	-0.87	1	1
TMEM189-UBE2V1	0	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.008	0.056	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
IL1RN	-0.4	0.6	-9999	-1.3	11	11
TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
MAP2K6	0	0	-9999	-10000	0	0

×

ceramide signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.052	0.006	-9999	-10000	0	0
BAG4	0	0	-9999	-10000	0	0
BAD	0.035	0.003	-9999	-10000	0	0
NFKBIA	0	0	-9999	-10000	0	0
BIRC3	-0.005	0.032	-9999	-10000	0	0
BAX	0.035	0.003	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.017	0.002	-9999	-10000	0	0
IKBKB	0.058	0.006	-9999	-10000	0	0
MAP2K2	0.048	0.003	-9999	-10000	0	0
MAP2K1	0.048	0.003	-9999	-10000	0	0
SMPD1	0.022	0.002	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.058	0.005	-9999	-10000	0	0
MAP2K4	0.042	0.003	-9999	-10000	0	0
protein ubiquitination	0.06	0.006	-9999	-10000	0	0
EnzymeConsortium:2.7.1.37	0.054	0.003	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
RAF1	0.043	0.003	-9999	-10000	0	0
CRADD	0	0	-9999	-10000	0	0
mol:ceramide	0.028	0.003	-9999	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-9999	-10000	0	0
MADD	0	0	-9999	-10000	0	0
MAP3K1	0.035	0.003	-9999	-10000	0	0
TRADD	0	0	-9999	-10000	0	0
RELA/p50	0	0	-9999	-10000	0	0
MAPK3	0.05	0.003	-9999	-10000	0	0
MAPK1	0.05	0.003	-9999	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-9999	-10000	0	0
FADD	0.052	0.006	-9999	-10000	0	0
KSR1	0.036	0.003	-9999	-10000	0	0
MAPK8	0.026	0.13	-9999	-0.74	1	1
TRAF2	0	0	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.058	0.006	-9999	-10000	0	0
TNF R/SODD	0	0	-9999	-10000	0	0
TNF	-0.005	0.032	-9999	-10000	0	0
CYCS	0.036	0.003	-9999	-10000	0	0
IKBKG	0.058	0.006	-9999	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.045	0.009	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
AIFM1	0.036	0.003	-9999	-10000	0	0
TNF/TNF R/SODD	-0.002	0.013	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.028	0.002	-9999	-10000	0	0
NSMAF	0.052	0.006	-9999	-10000	0	0
response to hydrogen peroxide	0	0	-9999	-10000	0	0
BCL2	0	0	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.002	0.009	-9999	-10000	0	0
VDR	-0.005	0.032	-9999	-10000	0	0
FAM120B	0	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.049	0.054	-9999	-10000	0	0
RXRs/LXRs/DNA/Oxysterols	-0.012	0.067	-9999	-0.41	1	1
MED1	0	0	-9999	-10000	0	0
mol:9cRA	0.005	0.01	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.039	0.13	-9999	-0.47	3	3
RXRs/NUR77	-0.002	0.009	-9999	-10000	0	0
RXRs/PPAR	-0.014	0.075	-9999	-0.46	1	1
NCOR2	0	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.003	0.021	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	-0.002	0.01	-9999	-10000	0	0
RARA	0	0	-9999	-10000	0	0
NCOA1	0	0	-9999	-10000	0	0
VDR/VDR/DNA	-0.005	0.032	-9999	-10000	0	0
RARs/RARs/DNA/9cRA	0	0	-9999	-10000	0	0
RARG	0	0	-9999	-10000	0	0
RPS6KB1	0.003	0.011	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.039	0.13	-9999	-0.47	3	3
THRA	0	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.003	0.021	-9999	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.003	0.021	-9999	-10000	0	0
NR1H4	-0.11	0.36	-9999	-1.3	3	3
RXRs/LXRs/DNA	-0.004	0.025	-9999	-10000	0	0
NR1H2	0.016	0.007	-9999	-10000	0	0
NR1H3	0.016	0.008	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	0	0.013	-9999	-10000	0	0
NR4A1	0	0	-9999	-10000	0	0
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.04	0.13	-9999	-0.46	3	3
RXRG	0.012	0.011	-9999	-10000	0	0
RXR alpha/CCPG	0	0	-9999	-10000	0	0
RXRA	0.015	0.007	-9999	-10000	0	0
RXRB	0.015	0.008	-9999	-10000	0	0
THRB	-0.11	0.36	-9999	-1.3	3	3
PPARG	-0.036	0.22	-9999	-1.3	1	1
PPARD	0	0	-9999	-10000	0	0
TNF	0.059	0.075	-9999	-10000	0	0
mol:Oxysterols	0.005	0.009	-9999	-10000	0	0
cholesterol transport	0.053	0.079	-9999	-0.41	1	1
PPARA	0	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0	0	-9999	-10000	0	0
RXRs/NUR77/BCL2	0	0.005	-9999	-10000	0	0
SREBF1	0.06	0.074	-9999	-10000	0	0
RXRs/RXRs/DNA/9cRA	-0.003	0.021	-9999	-10000	0	0
ABCA1	0.029	0.26	-9999	-1.5	1	1
RARs/THRs	-0.073	0.24	-9999	-0.87	3	3
RXRs/FXR	-0.077	0.25	-9999	-0.91	3	3
BCL2	0	0	-9999	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0	0	-10000	0	-10000	0	0
EPHB2	-0.064	0.09	-10000	0	-10000	0	0
EFNB1	-0.004	0.053	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.041	0.19	-10000	0	-0.8	2	2
Ephrin B2/EPHB1-2	-0.049	0.15	-10000	0	-0.92	1	1
neuron projection morphogenesis	-0.043	0.18	-10000	0	-0.76	2	2
Ephrin B1/EPHB1-2/Tiam1	-0.047	0.21	-10000	0	-0.87	2	2
DNM1	-0.032	0.072	-10000	0	-10000	0	0
cell-cell signaling	0	0.001	-10000	0	-10000	0	0
MAP2K4	0.026	0.005	-10000	0	-10000	0	0
YES1	0.006	0.007	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK2	-0.022	0.15	-10000	0	-0.87	1	1
PI3K	0	0	-10000	0	-10000	0	0
mol:GDP	-0.046	0.2	-10000	0	-0.86	2	2
ITGA2B	-0.021	0.061	-10000	0	-10000	0	0
endothelial cell proliferation	0	0	-10000	0	-10000	0	0
FYN	0.006	0.007	-10000	0	-10000	0	0
MAP3K7	0.01	0.009	-10000	0	-10000	0	0
FGR	0.008	0.007	-10000	0	-10000	0	0
TIAM1	-0.036	0.22	-10000	0	-1.3	1	1
PIK3R1	0	0	-10000	0	-10000	0	0
RGS3	0	0	-10000	0	-10000	0	0
cell adhesion	-0.005	0.016	-10000	0	-10000	0	0
LYN	0.006	0.007	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/Src Family Kinases	0.005	0.005	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2	0.003	0.006	-10000	0	-10000	0	0
SRC	0.008	0.007	-10000	0	-10000	0	0
ITGB3	0	0	-10000	0	-10000	0	0
EPHB1	-0.036	0.21	-10000	0	-1.3	1	1
EPHB4	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.013	0.035	-10000	0	-10000	0	0
BLK	0.006	0.007	-10000	0	-10000	0	0
HCK	0.006	0.007	-10000	0	-10000	0	0
regulation of stress fiber formation	0.022	0.15	0.85	1	-10000	0	1
MAPK8	0.008	0.15	-10000	0	-0.86	1	1
Ephrin B1/EPHB1-2/RGS3	-0.022	0.15	-10000	0	-0.87	1	1
endothelial cell migration	0.014	0.012	-10000	0	-10000	0	0
NCK2	0	0	-10000	0	-10000	0	0
PTPN13	-0.012	0.046	-10000	0	-10000	0	0
regulation of focal adhesion formation	0.022	0.15	0.85	1	-10000	0	1
chemotaxis	0.022	0.15	0.85	1	-10000	0	1
PIK3CA	0	0	-10000	0	-10000	0	0
Rac1/GTP	-0.042	0.19	-10000	0	-0.8	2	2
angiogenesis	0.005	0.006	-10000	0	-10000	0	0
LCK	0.008	0.007	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0	0	-9999	-10000	0	0
NFATC1	0.057	0	-9999	-10000	0	0
NFATC2	0.023	0.091	-9999	-0.47	1	1
NFATC3	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.019	0.074	-9999	-10000	0	0
Exportin 1/Ran/NUP214	0	0	-9999	-10000	0	0
mol:DAG	0.001	0	-9999	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.012	0.051	-9999	-10000	0	0
BCL2/BAX	0	0	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0	0	-9999	-10000	0	0
CaM/Ca2+	0	0	-9999	-10000	0	0
BAX	0	0	-9999	-10000	0	0
MAPK14	0	0	-9999	-10000	0	0
BAD	0	0	-9999	-10000	0	0
CABIN1/MEF2D	-0.014	0.06	-9999	-10000	0	0
Calcineurin A alpha-beta B1/BCL2	0	0	-9999	-10000	0	0
FKBP8	0	0	-9999	-10000	0	0
activation-induced cell death of T cells	0.014	0.059	-9999	-10000	0	0
KPNB1	0	0	-9999	-10000	0	0
KPNA2	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
SFN	-0.17	0.061	-9999	-10000	0	0
MAP3K8	0	0	-9999	-10000	0	0
NFAT4/CK1 alpha	0	0	-9999	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.014	0.065	-9999	-10000	0	0
CABIN1	0.019	0.074	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
MAP3K1	0	0	-9999	-10000	0	0
CAMK4	0	0	-9999	-10000	0	0
mol:Ca2+	0.001	0	-9999	-10000	0	0
MAPK3	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
MAPK8	-0.036	0.22	-9999	-1.3	1	1
MAPK9	0	0	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
FKBP1A	0	0	-9999	-10000	0	0
NFAT1-c-4/YWHAQ	-0.005	0.026	-9999	-10000	0	0
PRKCH	0	0	-9999	-10000	0	0
CABIN1/Cbp/p300	0	0	-9999	-10000	0	0
CASP3	0	0	-9999	-10000	0	0
PIM1	0	0	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-9999	-10000	0	0
apoptosis	0	0	-9999	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.015	0.005	-9999	-10000	0	0
PRKCB	-0.042	0.22	-9999	-1.3	1	1
PRKCE	0	0	-9999	-10000	0	0
JNK2/NFAT4	0	0	-9999	-10000	0	0
BAD/BCL-XL	0	0	-9999	-10000	0	0
PRKCD	0	0	-9999	-10000	0	0
NUP214	0	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
PRKCA	0	0	-9999	-10000	0	0
PRKCG	-0.011	0.044	-9999	-10000	0	0
PRKCQ	-0.036	0.22	-9999	-1.3	1	1
FKBP38/BCL2	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
PRKCB1	0	0	-9999	-10000	0	0
CSNK2A1	0	0	-9999	-10000	0	0
NFATc/JNK1	-0.021	0.13	-9999	-0.76	1	1
CaM/Ca2+/FKBP38	0	0	-9999	-10000	0	0
FKBP12/FK506	0	0	-9999	-10000	0	0
CSNK1A1	0.02	0	-9999	-10000	0	0
CaM/Ca2+/CAMK IV	0	0	-9999	-10000	0	0
NFATc/ERK1	0	0	-9999	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.012	0.051	-9999	-10000	0	0
NR4A1	-0.012	0.056	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
positive T cell selection	0	0	-9999	-10000	0	0
NFAT1/CK1 alpha	-0.014	0.061	-9999	-10000	0	0
RCH1/ KPNB1	0	0	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
AKAP5	0	0	-9999	-10000	0	0
MEF2D	0	0	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
YWHAZ	0	0	-9999	-10000	0	0
NFATc/p38 alpha	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
BCL2	0	0	-9999	-10000	0	0

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.025	0.034	-9999	-10000	0	0
PTK2B	0	0	-9999	-10000	0	0
mol:Ca2+	0.053	0.12	-9999	-10000	0	0
EDN1	0.02	0.027	-9999	-10000	0	0
EDN3	-0.011	0.044	-9999	-10000	0	0
EDN2	-0.005	0.032	-9999	-10000	0	0
HRAS/GDP	0.033	0.13	-9999	-10000	0	0
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.04	0.094	-9999	-10000	0	0
ADCY4	0.017	0.025	-9999	-10000	0	0
ADCY5	0.017	0.025	-9999	-10000	0	0
ADCY6	0.017	0.025	-9999	-10000	0	0
ADCY7	0.017	0.025	-9999	-10000	0	0
ADCY1	-0.054	0.24	-9999	-0.84	3	3
ADCY2	0.017	0.032	-9999	-10000	0	0
ADCY3	0.017	0.025	-9999	-10000	0	0
ADCY8	0.022	0.028	-9999	-10000	0	0
ADCY9	0.017	0.025	-9999	-10000	0	0
arachidonic acid secretion	0.033	0.16	-9999	-0.42	1	1
ETB receptor/Endothelin-1/Gq/GTP	-0.019	0.18	-9999	-0.46	5	5
GNAO1	-0.54	0.64	-9999	-1.3	15	15
HRAS	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.045	0.06	-9999	-10000	0	0
ETA receptor/Endothelin-1/Gs/GTP	0.043	0.055	-9999	-10000	0	0
mol:GTP	0.002	0.003	-9999	-10000	0	0
COL3A1	0.025	0.034	-9999	-10000	0	0
EDNRB	-0.096	0.36	-9999	-1.3	3	3
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	0.025	0.034	-9999	-10000	0	0
CYSLTR1	0.025	0.034	-9999	-10000	0	0
SLC9A1	0.018	0.025	-9999	-10000	0	0
mol:GDP	0.028	0.14	-9999	-10000	0	0
SLC9A3	0.011	0.16	-9999	-0.52	3	3
RAF1	0.016	0.16	-9999	-0.52	1	1
JUN	0.053	0.12	-9999	-10000	0	0
JAK2	0.025	0.034	-9999	-10000	0	0
mol:IP3	0.014	0.14	-9999	-0.44	2	2
ETA receptor/Endothelin-1	0.049	0.065	-9999	-10000	0	0
PLCB1	-0.005	0.031	-9999	-10000	0	0
PLCB2	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-3	0.007	0.036	-9999	-10000	0	0
FOS	-0.028	0.33	-9999	-1.1	3	3
Gai/GDP	-0.33	0.4	-9999	-0.79	15	15
CRK	0	0	-9999	-10000	0	0
mol:Ca ++	0.034	0.14	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
PRKCB1	0.015	0.14	-9999	-0.42	2	2
GNAQ	0.012	0.004	-9999	-10000	0	0
GNAZ	-0.032	0.072	-9999	-10000	0	0
GNAL	-0.005	0.032	-9999	-10000	0	0
Gs family/GDP	-0.038	0.096	-9999	-10000	0	0
ETA receptor/Endothelin-1/Gq/GTP	0.038	0.12	-9999	-0.44	2	2
MAPK14	0.007	0.14	-9999	-0.4	1	1
TRPC6	0.053	0.13	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GNAI1	0	0	-9999	-10000	0	0
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.001	0.14	-9999	-0.39	2	2
ETB receptor/Endothelin-2	-0.093	0.3	-9999	-1.1	3	3
ETB receptor/Endothelin-3	-0.097	0.3	-9999	-1.1	3	3
ETB receptor/Endothelin-1	-0.071	0.3	-9999	-1.1	3	3
MAPK3	-0.007	0.27	-9999	-0.81	3	3
MAPK1	-0.007	0.27	-9999	-0.81	3	3
Rac1/GDP	0.011	0.13	-9999	-10000	0	0
cAMP biosynthetic process	0.07	0.082	-9999	-10000	0	0
MAPK8	0.045	0.14	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.19	0.3	-9999	-0.69	5	5
p130Cas/CRK/Src/PYK2	0.049	0.14	-9999	-10000	0	0
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	0.011	0.13	-9999	-10000	0	0
COL1A2	-0.025	0.18	-9999	-10000	0	0
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	0.014	0.029	-9999	-10000	0	0
mol:DAG	0.014	0.14	-9999	-0.44	2	2
MAP2K2	0.009	0.2	-9999	-0.69	1	1
MAP2K1	0.009	0.2	-9999	-0.69	1	1
EDNRA	0.019	0.026	-9999	-10000	0	0
positive regulation of muscle contraction	0.025	0.035	-9999	-10000	0	0
Gq family/GDP	-0.063	0.18	-9999	-0.79	2	2
HRAS/GTP	0.017	0.15	-9999	-0.39	3	3
PRKCH	0.024	0.14	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.024	0.14	-9999	-10000	0	0
PRKCB	-0.004	0.19	-9999	-0.81	1	1
PRKCE	0.024	0.14	-9999	-10000	0	0
PRKCD	0.024	0.14	-9999	-10000	0	0
PRKCG	0.017	0.14	-9999	-10000	0	0
regulation of vascular smooth muscle contraction	-0.039	0.38	-9999	-1.3	3	3
PRKCQ	-0.002	0.19	-9999	-0.81	1	1
PLA2G4A	0.032	0.17	-9999	-0.45	1	1
GNA14	-0.061	0.3	-9999	-1.3	2	2
GNA15	0.01	0.005	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
GNA11	0.01	0.005	-9999	-10000	0	0
Rac1/GTP	0.045	0.06	-9999	-10000	0	0
MMP1	-0.052	0.07	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.001	0.009	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0	0.002	-9999	-10000	0	0
SUMO1	0	0	-9999	-10000	0	0
ZFPM1	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
FKBP3	0	0	-9999	-10000	0	0
Histones	0	0.002	-9999	-10000	0	0
YY1/LSF	0	0	-9999	-10000	0	0
SMG5	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.001	0.004	-9999	-10000	0	0
I kappa B alpha/HDAC1	0	0.002	-9999	-10000	0	0
SAP18	0	0	-9999	-10000	0	0
RELA	0	0.002	-9999	-10000	0	0
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
HDAC3/TR2	0	0.002	-9999	-10000	0	0
NuRD/MBD3 Complex	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.005	0.032	-9999	-10000	0	0
GATA1	0	0	-9999	-10000	0	0
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0	0	-9999	-10000	0	0
RBBP7	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0	0	-9999	-10000	0	0
MAX	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NFKBIA	-0.001	0.004	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0	0	-9999	-10000	0	0
SIN3 complex	0	0	-9999	-10000	0	0
SMURF1	0	0	-9999	-10000	0	0
CHD3	0	0	-9999	-10000	0	0
SAP30	0	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0	0	-9999	-10000	0	0
YY1/HDAC3	0	0.002	-9999	-10000	0	0
YY1/HDAC2	0	0	-9999	-10000	0	0
YY1/HDAC1	0	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0	0	-9999	-10000	0	0
PPARG	-0.014	0.082	-9999	-0.5	1	1
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0	0.002	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0	0	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC3	-0.001	0.004	-9999	-10000	0	0
HDAC2	0	0	-9999	-10000	0	0
YY1	0	0	-9999	-10000	0	0
HDAC8	0	0	-9999	-10000	0	0
SMAD7	0	0	-9999	-10000	0	0
NCOR2	0	0	-9999	-10000	0	0
MXD1	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0	0	-9999	-10000	0	0
YY1/SAP30/HDAC1	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.004	-9999	-10000	0	0
histone deacetylation	0.046	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0	0.001	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GATAD2B	0	0	-9999	-10000	0	0
GATAD2A	0	0	-9999	-10000	0	0
GATA2/HDAC3	-0.002	0.01	-9999	-10000	0	0
GATA1/HDAC1	0	0	-9999	-10000	0	0
GATA1/HDAC3	0	0.002	-9999	-10000	0	0
CHD4	0	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.003	0.019	-9999	-10000	0	0
SIN3/HDAC complex/Mad/Max	0	0	-9999	-10000	0	0
NuRD Complex	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0	0.002	-9999	-10000	0	0
SIN3B	0	0	-9999	-10000	0	0
MTA2	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
HDAC complex	0	0	-9999	-10000	0	0
GATA1/Fog1	0	0	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.005	0.032	-9999	-10000	0	0
negative regulation of cell growth	0.046	0	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0	0.001	-9999	-10000	0	0
SIN3/HDAC complex/NCoR1	0	0	-9999	-10000	0	0
TFCP2	0	0	-9999	-10000	0	0
NR2C1	0	0	-9999	-10000	0	0
MBD3	0	0	-9999	-10000	0	0
MBD2	0	0	-9999	-10000	0	0

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
CDKN2A	-0.015	0.054	-9999	-9999
TP53	-0.007	0.014	-9999	-9999
Senescence	-0.007	0.014	-9999	-9999
Apoptosis	-0.007	0.014	-9999	-9999
Activated_Oncogenes	0	0	-9999	-9999
MDM2	0.014	0.028	-9999	-9999
MDM4	0	0	-9999	-9999

×

FAS signaling pathway (CD95)

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.001	0.003	-9999	-10000	0	0
RFC1	0.001	0.003	-9999	-10000	0	0
PRKDC	0.001	0.003	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
CASP7	-0.001	0.018	-9999	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.007	0.085	-9999	-0.5	1	1
MAP2K4	0.046	0.059	-9999	-10000	0	0
mol:ceramide	-0.012	0.071	-9999	-10000	0	0
GSN	0.001	0.003	-9999	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	-0.003	0.063	-9999	-10000	0	0
FAS	-0.036	0.22	-9999	-1.3	1	1
BID	0.001	0.005	-9999	-10000	0	0
MAP3K1	0.037	0.037	-9999	-10000	0	0
MAP3K7	0	0	-9999	-10000	0	0
RB1	0.001	0.003	-9999	-10000	0	0
CFLAR	0	0	-9999	-10000	0	0
HGF/MET	-0.17	0.36	-9999	-0.98	6	6
ARHGDIB	0.001	0.003	-9999	-10000	0	0
FADD	0	0	-9999	-10000	0	0
actin filament polymerization	-0.001	0.003	-9999	-10000	0	0
NFKB1	-0.003	0.016	-9999	-10000	0	0
MAPK8	0.03	0.15	-9999	-0.78	1	1
DFFA	0.001	0.003	-9999	-10000	0	0
DNA fragmentation during apoptosis	0.001	0.003	-9999	-10000	0	0
FAS/FADD/MET	-0.027	0.16	-9999	-0.98	1	1
CFLAR/RIP1	0	0	-9999	-10000	0	0
FAIM3	-0.005	0.032	-9999	-10000	0	0
FAF1	0	0	-9999	-10000	0	0
PARP1	0.001	0.003	-9999	-10000	0	0
DFFB	0.001	0.003	-9999	-10000	0	0
CHUK	-0.002	0.013	-9999	-10000	0	0
FASLG	0	0	-9999	-10000	0	0
FAS/FADD	-0.03	0.18	-9999	-1.1	1	1
HGF	-0.22	0.49	-9999	-1.3	6	6
LMNA	0.001	0.004	-9999	-10000	0	0
CASP6	0.001	0.003	-9999	-10000	0	0
CASP10	0	0	-9999	-10000	0	0
CASP3	0	0.003	-9999	-10000	0	0
PTPN13	-0.016	0.053	-9999	-10000	0	0
CASP8	0.002	0.011	-9999	-10000	0	0
IL6	0.025	0.042	-9999	-10000	0	0
MET	0	0	-9999	-10000	0	0
ICAD/CAD	0.001	0.005	-9999	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.012	0.072	-9999	-10000	0	0
activation of caspase activity by cytochrome c	0.001	0.005	-9999	-10000	0	0
PAK2	0.001	0.003	-9999	-10000	0	0
BCL2	0	0	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
EEF2K	0.018	0.035	-9999	-9999
SNTA1	0	0	-9999	-9999
response to hypoxia	0	0	-9999	-9999
STMN1	0.018	0.035	-9999	-9999
MAPK12	0.021	0.031	-9999	-9999
CCND1	0.017	0.015	-9999	-9999
p38 gamma/SNTA1	-0.006	0.017	-9999	-9999
MAP2K3	0	0	-9999	-9999
PKN1	0	0	-9999	-9999
G2/M transition checkpoint	0.021	0.031	-9999	-9999
MAP2K6	0.025	0	-9999	-9999
MAPT	0.021	0.025	-9999	-9999
MAPK13	0.007	0.043	-9999	-9999
hyperosmotic response	0	0	-9999	-9999
ZAK	0	0	-9999	-9999

×

Retinoic acid receptors-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-9999	-10000	0	0
HDAC3	0	0	-9999	-10000	0	0
VDR	-0.005	0.032	-9999	-10000	0	0
Cbp/p300/PCAF	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.041	0.026	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
MAPK14	0	0	-9999	-10000	0	0
AKT1	0.021	0.032	-9999	-10000	0	0
RAR alpha/9cRA/Cyclin H	-0.01	0.059	-9999	-10000	0	0
mol:9cRA	0	0	-9999	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.039	0.026	-9999	-10000	0	0
CDC2	0.001	0	-9999	-10000	0	0
response to UV	0.001	0	-9999	-10000	0	0
RAR alpha/Jnk1	-0.03	0.18	-9999	-1.1	1	1
NCOR2	0	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.003	0.021	-9999	-10000	0	0
RXRs/RARs/NRIP1/9cRA	0.052	0.046	-9999	-10000	0	0
NCOA2	-0.073	0.3	-9999	-1.3	2	2
NCOA3	0	0	-9999	-10000	0	0
NCOA1	0	0	-9999	-10000	0	0
VDR/VDR/DNA	-0.005	0.032	-9999	-10000	0	0
RARG	0	0	-9999	-10000	0	0
RAR gamma1/9cRA	0	0	-9999	-10000	0	0
MAPK3	0	0	-9999	-10000	0	0
MAPK1	0	0	-9999	-10000	0	0
MAPK8	-0.036	0.21	-9999	-1.3	1	1
mol:Vit D3	0	0	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.003	0.044	-9999	-10000	0	0
RARA	0.016	0.069	-9999	-0.39	1	1
negative regulation of phosphoinositide 3-kinase cascade	0	0	-9999	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.017	0.11	-9999	-0.42	2	2
PRKCA	0.014	0	-9999	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.047	0.042	-9999	-10000	0	0
RXRG	0.022	0.014	-9999	-10000	0	0
RXRA	0.024	0.067	-9999	-0.37	1	1
RXRB	0.024	0.014	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.003	0.021	-9999	-10000	0	0
RBP1	0	0	-9999	-10000	0	0
CRBP1/9-cic-RA	0	0	-9999	-10000	0	0
RARB	0.013	0	-9999	-10000	0	0
PRKCG	0	0.046	-9999	-10000	0	0
MNAT1	0	0	-9999	-10000	0	0
RAR alpha/RXRs	0.008	0.054	-9999	-10000	0	0
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.05	0.044	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.04	0.051	-9999	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	0.047	0.042	-9999	-10000	0	0
positive regulation of DNA binding	-0.009	0.056	-9999	-10000	0	0
NRIP1	0.046	0.037	-9999	-10000	0	0
RXRs/RARs	0.041	0.039	-9999	-10000	0	0
RXRs/RXRs/DNA/9cRA	-0.006	0.044	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
CDK7	0	0	-9999	-10000	0	0
TFIIH	0	0	-9999	-10000	0	0
RAR alpha/9cRA	-0.007	0.04	-9999	-10000	0	0
CCNH	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
RAR gamma2/9cRA	0	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.03	0.18	-9999	-1.1	1	1
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0	0	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	-0.025	0.15	-9999	-0.92	1	1
lamellipodium assembly	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
TLN1	0	0	-9999	-10000	0	0
PXN	0.022	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0	0	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.036	0.22	-9999	-1.3	1	1
ARF6/GDP	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.049	0.2	-9999	-0.87	2	2
p130Cas/Crk/Dock1	0	0	-9999	-10000	0	0
VCAM1	-0.073	0.3	-9999	-1.3	2	2
alpha4/beta1 Integrin/Paxillin/Talin	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GIT1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0	0	-9999	-10000	0	0
Rac1/GTP	0	0	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.027	0.16	-9999	-0.98	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0	0.002	-9999	-10000	0	0
NFKBIA	0.028	0.011	-9999	-10000	0	0
MAPK14	0	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0	0	-9999	-10000	0	0
ARRB2	0	0	-9999	-10000	0	0
REL	-0.036	0.22	-9999	-1.3	1	1
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
NFKB1	0.022	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	-0.001	0.005	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0	0.001	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.001	0.005	-9999	-10000	0	0
IKBKB	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
SYK	-0.005	0.032	-9999	-10000	0	0
I kappa B alpha/PIK3R1	-0.001	0.005	-9999	-10000	0	0
cell death	0	0.001	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.027	0.16	-9999	-0.98	1	1
LCK	-0.005	0.032	-9999	-10000	0	0
BCL3	0	0	-9999	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.022	0.13	-9999	-0.8	1	1
Syndecan-3/Neurocan	0	0	-9999	-10000	0	0
POMC	-0.005	0.032	-9999	-10000	0	0
EGFR	-0.073	0.3	-9999	-1.3	2	2
Syndecan-3/EGFR	-0.048	0.2	-9999	-0.87	2	2
AGRP	0	0	-9999	-10000	0	0
NCSTN	0	0	-9999	-10000	0	0
PSENEN	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0	0	-9999	-10000	0	0
APH1A	0	0	-9999	-10000	0	0
NCAN	0	0	-9999	-10000	0	0
long-term memory	0	0	-9999	-10000	0	0
Syndecan-3/IL8	-0.034	0.14	-9999	-0.87	1	1
PSEN1	0	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	0	0	-9999	-10000	0	0
limb bud formation	0	0	-9999	-10000	0	0
MC4R	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
PTN	-0.036	0.22	-9999	-1.3	1	1
FGFR/FGF/Syndecan-3	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.021	0.12	-9999	-0.76	1	1
Syndecan-3/AgRP	0	0	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	0	0	-9999	-10000	0	0
Fyn/Cortactin	0	0	-9999	-10000	0	0
SDC3	0	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.034	0.14	-9999	-0.85	1	1
IL8	-0.068	0.22	-9999	-1.3	1	1
Syndecan-3/Fyn/Cortactin	0	0	-9999	-10000	0	0
Syndecan-3/CASK	0	0	-9999	-10000	0	0
alpha-MSH/MC4R	-0.003	0.019	-9999	-10000	0	0
Gamma Secretase	0	0	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
BCL2L1	0.061	0.016	-9999	-9999
UGCG	0.001	0.006	-9999	-9999
AKT1/mTOR/p70S6K/Hsp90/TERT	0.082	0.019	-9999	-9999
mol:GTP	0	0	-9999	-9999
mol:glucosylceramide	0.03	0.005	-9999	-9999
mol:DAG	0	0	-9999	-9999
CaM/Ca2+/Calcineurin A alpha-beta B1	0	0.001	-9999	-9999
FRAP1	0.091	0.019	-9999	-9999
FOXO3	0.093	0.018	-9999	-9999
AKT1	0.088	0.018	-9999	-9999
GAB2	0	0	-9999	-9999
SMPD1	0.001	0.006	-9999	-9999
SGMS1	0.001	0.006	-9999	-9999
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-9999
mol:Ca2+	0	0	-9999	-9999
mol:GDP	0.023	0	-9999	-9999
CALM1	0	0	-9999	-9999
cell proliferation	0.055	0.01	-9999	-9999
EIF3A	0	0	-9999	-9999
PI3K	0	0	-9999	-9999
RPS6KB1	0.025	0.014	-9999	-9999
mol:sphingomyelin	0	0	-9999	-9999
natural killer cell activation	0.001	0	-9999	-9999
JAK3	0.008	0.033	-9999	-9999
PIK3R1	0.013	0.002	-9999	-9999
JAK1	0.013	0.002	-9999	-9999
NFKB1	0	0	-9999	-9999
MYC	0.091	0.017	-9999	-9999
MYB	0.024	0.034	-9999	-9999
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.079	0.02	-9999	-9999
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0	0.001	-9999	-9999
mol:PI-3-4-5-P3	0.079	0.019	-9999	-9999
Rac1/GDP	0	0	-9999	-9999
T cell proliferation	0.083	0.019	-9999	-9999
SHC1	0	0	-9999	-9999
RAC1	0	0	-9999	-9999
positive regulation of cyclin-dependent protein kinase activity	0.004	0.005	-9999	-9999
PRKCZ	0.084	0.019	-9999	-9999
NF kappa B1 p50/RelA	0	0	-9999	-9999
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.001	0.007	-9999	-9999
HSP90AA1	0	0	-9999	-9999
RELA	0	0	-9999	-9999
IL2RA	-0.016	0.053	-9999	-9999
IL2RB	0.013	0.002	-9999	-9999
TERT	-0.016	0.053	-9999	-9999
E2F1	0.023	0.023	-9999	-9999
SOS1	0	0	-9999	-9999
RPS6	0	0	-9999	-9999
mol:cAMP	-0.002	0.003	-9999	-9999
PTPN11	0	0	-9999	-9999
IL2RG	0.008	0.033	-9999	-9999
actin cytoskeleton organization	0.083	0.019	-9999	-9999
GRB2	0	0	-9999	-9999
IL2	0.007	0.005	-9999	-9999
PIK3CA	0.013	0.002	-9999	-9999
Rac1/GTP	0.029	0.01	-9999	-9999
LCK	0.008	0.033	-9999	-9999
BCL2	0.092	0.017	-9999	-9999

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.001	0.29	-9999	-1.7	1	1
MKNK1	0	0	-9999	-10000	0	0
MAPK14	0.017	0.057	-9999	-10000	0	0
ATF2/c-Jun	0.034	0.045	-9999	-10000	0	0
MAPK11	0.017	0.057	-9999	-10000	0	0
MITF	0.032	0.07	-9999	-10000	0	0
MAPKAPK5	0.034	0.069	-9999	-10000	0	0
KRT8	0.018	0.12	-9999	-0.55	1	1
MAPKAPK3	0	0	-9999	-10000	0	0
MAPKAPK2	0	0	-9999	-10000	0	0
p38alpha-beta/CK2	0.025	0.086	-9999	-10000	0	0
CEBPB	0.034	0.069	-9999	-10000	0	0
SLC9A1	0.034	0.069	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.04	0.068	-9999	-10000	0	0
p38alpha-beta/MNK1	-0.01	0.062	-9999	-10000	0	0
JUN	0.035	0.045	-9999	-10000	0	0
PPARGC1A	0.001	0.15	-9999	-0.55	2	2
USF1	0.034	0.069	-9999	-10000	0	0
RAB5/GDP/GDI1	-0.007	0.044	-9999	-10000	0	0
NOS2	0.032	0.073	-9999	-10000	0	0
DDIT3	0.034	0.069	-9999	-10000	0	0
RAB5A	0	0	-9999	-10000	0	0
HSPB1	0.039	0.057	-9999	-10000	0	0
p38alpha-beta/HBP1	-0.01	0.062	-9999	-10000	0	0
CREB1	0.039	0.072	-9999	-10000	0	0
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	0.037	0.062	-9999	-10000	0	0
RPS6KA4	0.034	0.069	-9999	-10000	0	0
PLA2G4A	0.034	0.063	-9999	-10000	0	0
GDI1	0.034	0.069	-9999	-10000	0	0
TP53	0.037	0.086	-9999	-10000	0	0
RPS6KA5	0.034	0.069	-9999	-10000	0	0
ESR1	-0.4	0.33	-9999	-0.59	25	25
HBP1	0	0	-9999	-10000	0	0
MEF2C	0.034	0.069	-9999	-10000	0	0
MEF2A	0.034	0.069	-9999	-10000	0	0
EIF4EBP1	0.039	0.072	-9999	-10000	0	0
KRT19	-0.032	0.12	-9999	-0.49	2	2
ELK4	0.034	0.069	-9999	-10000	0	0
ATF6	0.034	0.069	-9999	-10000	0	0
ATF1	0.039	0.072	-9999	-10000	0	0
p38alpha-beta/MAPKAPK2	-0.01	0.062	-9999	-10000	0	0
p38alpha-beta/MAPKAPK3	-0.01	0.062	-9999	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.011	0.053	-9999	-10000	0	0
FYN	0.053	0.087	-9999	-10000	0	0
LAT/GRAP2/SLP76	-0.014	0.058	-9999	-10000	0	0
IKBKB	0	0	-9999	-10000	0	0
AKT1	0.06	0.067	-9999	-10000	0	0
B2M	0	0	-9999	-10000	0	0
IKBKG	0	0.016	-9999	-10000	0	0
MAP3K8	0	0	-9999	-10000	0	0
mol:Ca2+	-0.003	0.009	-9999	-10000	0	0
integrin-mediated signaling pathway	0	0	-9999	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.063	0.085	-9999	-10000	0	0
TRPV6	-0.011	0.047	-9999	-10000	0	0
CD28	0	0	-9999	-10000	0	0
SHC1	0.055	0.081	-9999	-10000	0	0
receptor internalization	0.04	0.1	-9999	-0.55	1	1
PRF1	0.014	0.25	-9999	-1.5	1	1
KRAS	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
COT/AKT1	0.058	0.056	-9999	-10000	0	0
LAT	0.05	0.085	-9999	-10000	0	0
EntrezGene:6955	0.001	0.002	-9999	-10000	0	0
CD3D	-0.011	0.044	-9999	-10000	0	0
CD3E	0.006	0.034	-9999	-10000	0	0
CD3G	-0.042	0.22	-9999	-1.3	1	1
RASGRP2	0	0.005	-9999	-10000	0	0
RASGRP1	0.065	0.072	-9999	-10000	0	0
HLA-A	0.011	0.004	-9999	-10000	0	0
RASSF5	0	0	-9999	-10000	0	0
RAP1A/GTP/RAPL	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:GDP	0.044	0.028	-9999	-10000	0	0
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.001	0.028	-9999	-10000	0	0
PRKCA	-0.008	0.033	-9999	-10000	0	0
GRAP2	-0.005	0.032	-9999	-10000	0	0
mol:IP3	-0.006	0.058	-9999	-10000	0	0
EntrezGene:6957	0.002	0.004	-9999	-10000	0	0
TCR/CD3/MHC I/CD8	0.029	0.086	-9999	-0.47	1	1
ORAI1	0.009	0.033	-9999	-10000	0	0
CSK	0.053	0.077	-9999	-10000	0	0
B7 family/CD28	-0.015	0.077	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.048	0.087	-9999	-0.43	1	1
PTPN6	0.051	0.078	-9999	-10000	0	0
VAV1	0.052	0.084	-9999	-10000	0	0
Monovalent TCR/CD3	0.008	0.098	-9999	-0.56	1	1
CBL	0	0	-9999	-10000	0	0
LCK	0.05	0.083	-9999	-10000	0	0
PAG1	0.053	0.077	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.011	0.076	-9999	-0.44	1	1
CD80	0	0	-9999	-10000	0	0
CD86	0	0	-9999	-10000	0	0
PDK1/CARD11/BCL10/MALT1	0.002	0.038	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
GO:0035030	-0.013	0.067	-9999	-10000	0	0
CD8A	0	0	-9999	-10000	0	0
CD8B	0.011	0.004	-9999	-10000	0	0
PTPRC	-0.036	0.22	-9999	-1.3	1	1
PDK1/PKC theta	0.068	0.088	-9999	-10000	0	0
CSK/PAG1	0.058	0.071	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
peptide-MHC class I	0	0	-9999	-10000	0	0
GRAP2/SLP76	-0.015	0.063	-9999	-10000	0	0
STIM1	0.005	0.016	-9999	-10000	0	0
RAS family/GTP	0.055	0.035	-9999	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.04	0.11	-9999	-0.57	1	1
mol:DAG	-0.012	0.046	-9999	-10000	0	0
RAP1A/GDP	0.02	0.012	-9999	-10000	0	0
PLCG1	0	0	-9999	-10000	0	0
CD247	-0.005	0.031	-9999	-10000	0	0
cytotoxic T cell degranulation	0.018	0.23	-9999	-1.3	1	1
RAP1A/GTP	0	0.001	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.061	0.076	-9999	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.008	0.069	-9999	-10000	0	0
NRAS	0	0	-9999	-10000	0	0
ZAP70	-0.005	0.032	-9999	-10000	0	0
GRB2/SOS1	0	0	-9999	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.016	0.062	-9999	-10000	0	0
MALT1	0	0	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
CD8 heterodimer	0	0	-9999	-10000	0	0
CARD11	-0.043	0.08	-9999	-10000	0	0
PRKCB	-0.021	0.095	-9999	-0.56	1	1
PRKCE	-0.008	0.033	-9999	-10000	0	0
PRKCQ	0.061	0.094	-9999	-10000	0	0
LCP2	0	0	-9999	-10000	0	0
BCL10	0	0	-9999	-10000	0	0
regulation of survival gene product expression	0.058	0.06	-9999	-10000	0	0
IKK complex	0.05	0.034	-9999	-10000	0	0
RAS family/GDP	0	0.002	-9999	-10000	0	0
MAP3K14	0.057	0.046	-9999	-10000	0	0
PDPK1	0.063	0.065	-9999	-10000	0	0
TCR/CD3/MHC I/CD8/Fyn	0.042	0.079	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0	0	-9999	-10000	0	0
Caspase 8 (4 units)	-0.011	0.068	-9999	-10000	0	0
NEF	0	0	-9999	-10000	0	0
NFKBIA	-0.001	0.004	-9999	-10000	0	0
BIRC3	-0.004	0.024	-9999	-10000	0	0
CYCS	0.042	0.073	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
CD247	-0.005	0.03	-9999	-10000	0	0
MAP2K7	0.045	0.048	-9999	-10000	0	0
protein ubiquitination	0.073	0.008	-9999	-10000	0	0
CRADD	0	0	-9999	-10000	0	0
DAXX	0	0	-9999	-10000	0	0
FAS	-0.036	0.22	-9999	-1.3	1	1
BID	-0.012	0.068	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	-0.002	0.013	-9999	-10000	0	0
TRADD	0	0	-9999	-10000	0	0
MAP3K5	0	0	-9999	-10000	0	0
CFLAR	0	0	-9999	-10000	0	0
FADD	0	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.002	0.013	-9999	-10000	0	0
MAPK8	0.028	0.14	-9999	-0.77	1	1
APAF1	0	0	-9999	-10000	0	0
TRAF1	0	0	-9999	-10000	0	0
TRAF2	0	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.012	0.073	-9999	-0.44	1	1
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.002	0.008	-9999	-10000	0	0
CHUK	0.075	0.008	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.024	0.14	-9999	-0.87	1	1
TCRz/NEF	-0.003	0.018	-9999	-10000	0	0
TNF	-0.005	0.032	-9999	-10000	0	0
FASLG	0.025	0.017	-9999	-10000	0	0
NFKB1	-0.001	0.004	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.002	0.013	-9999	-10000	0	0
CASP6	-0.007	0.05	-9999	-10000	0	0
CASP7	0.077	0.06	-9999	-10000	0	0
RELA	-0.001	0.004	-9999	-10000	0	0
CASP2	0	0	-9999	-10000	0	0
CASP3	0.077	0.06	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
TNFR1A/BAG4	0	0	-9999	-10000	0	0
CASP8	0	0	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
MAP3K14	0.07	0.008	-9999	-10000	0	0
APAF-1/Caspase 9	-0.008	0.041	-9999	-10000	0	0
BCL2	0.036	0.13	-9999	-0.68	1	1

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0.002	-9999	-10000	0	0
AES	0	0.002	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
LRP6/FZD1	0	0	-9999	-10000	0	0
SMAD4	0	0	-9999	-10000	0	0
DKK2	0	0	-9999	-10000	0	0
TLE1	0	0.002	-9999	-10000	0	0
MACF1	0	0	-9999	-10000	0	0
CTNNB1	0.037	0.016	-9999	-10000	0	0
WIF1	-0.048	0.084	-9999	-10000	0	0
beta catenin/RanBP3	0	0	-9999	-10000	0	0
KREMEN2	-0.043	0.08	-9999	-10000	0	0
DKK1	-0.075	0.094	-9999	-10000	0	0
beta catenin/beta TrCP1	0.009	0.023	-9999	-10000	0	0
FZD1	0	0	-9999	-10000	0	0
AXIN2	0.018	0.024	-9999	-10000	0	0
AXIN1	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
Axin1/APC/GSK3/beta catenin	0	0	-9999	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.046	0.074	-9999	-10000	0	0
Axin1/APC/GSK3	0	0	-9999	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.05	0.005	-9999	-10000	0	0
HNF1A	-0.036	0.22	-9999	-1.3	1	1
CTBP1	0	0.002	-9999	-10000	0	0
MYC	0.021	0.015	-9999	-10000	0	0
RANBP3	0	0	-9999	-10000	0	0
DKK2/LRP6/Kremen 2	-0.018	0.034	-9999	-10000	0	0
NKD1	-0.005	0.032	-9999	-10000	0	0
TCF4	0	0.002	-9999	-10000	0	0
TCF3	0	0.002	-9999	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0	0	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.009	0.058	-9999	-10000	0	0
LEF1	-0.022	0.062	-9999	-10000	0	0
DVL1	0.01	0.018	-9999	-10000	0	0
CSNK2A1	0	0	-9999	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.062	0.074	-9999	-10000	0	0
DKK1/LRP6/Kremen 2	-0.052	0.061	-9999	-10000	0	0
LRP6	0	0	-9999	-10000	0	0
CSNK1A1	0	0.002	-9999	-10000	0	0
NLK	0	0	-9999	-10000	0	0
CCND1	0.021	0.015	-9999	-10000	0	0
WNT1	0	0	-9999	-10000	0	0
GSK3A	0	0	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
FRAT1	0	0	-9999	-10000	0	0
PPP2R5D	0.007	0.018	-9999	-10000	0	0
APC	0	0	-9999	-10000	0	0
WNT1/LRP6/FZD1	0.017	0.03	-9999	-10000	0	0
CREBBP	0	0.002	-9999	-10000	0	0

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.052	0.066	-10000	0	-10000	0	0
cell-cell adhesion	0.026	0.11	0.68	1	-10000	0	1
Ephrin B/EPHB2/RasGAP	0.018	0.024	-10000	0	-10000	0	0
ITSN1	0	0	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.018	0.036	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.03	0.16	-10000	0	-0.99	1	1
HRAS/GDP	-0.019	0.12	-10000	0	-0.7	1	1
Ephrin B/EPHB1/GRB7	-0.047	0.2	-10000	0	-0.87	2	2
Endophilin/SYNJ1	-0.017	0.022	-10000	0	-10000	0	0
KRAS	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.023	0.14	-10000	0	-0.87	1	1
endothelial cell migration	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
GRB7	-0.036	0.22	-10000	0	-1.3	1	1
PAK1	-0.014	0.018	-10000	0	-10000	0	0
HRAS	0	0	-10000	0	-10000	0	0
RRAS	-0.017	0.022	-10000	0	-10000	0	0
DNM1	-0.032	0.072	-10000	0	-10000	0	0
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.024	0.14	-10000	0	-0.83	1	1
lamellipodium assembly	-0.026	0.11	-10000	0	-0.68	1	1
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.013	0.076	-10000	0	-0.46	1	1
PIK3R1	0	0	-10000	0	-10000	0	0
EPHB2	-0.064	0.091	-10000	0	-10000	0	0
EPHB3	-0.032	0.072	-10000	0	-10000	0	0
EPHB1	-0.036	0.22	-10000	0	-1.3	1	1
EPHB4	0	0	-10000	0	-10000	0	0
mol:GDP	0.004	0.099	-10000	0	-0.56	1	1
Ephrin B/EPHB2	-0.021	0.028	-10000	0	-10000	0	0
Ephrin B/EPHB3	-0.011	0.023	-10000	0	-10000	0	0
JNK cascade	-0.041	0.14	-10000	0	-0.84	1	1
Ephrin B/EPHB1	-0.026	0.14	-10000	0	-0.88	1	1
RAP1/GDP	-0.009	0.08	-10000	0	-10000	0	0
EFNB2	0	0	-10000	0	-10000	0	0
EFNB3	0	0	-10000	0	-10000	0	0
EFNB1	-0.005	0.032	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.05	0.15	-10000	0	-0.92	1	1
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.012	0.12	-10000	0	-0.71	1	1
Rap1/GTP	-0.023	0.11	-10000	0	-0.7	1	1
axon guidance	-0.052	0.066	-10000	0	-10000	0	0
MAPK3	0.039	0.075	-10000	0	-10000	0	0
MAPK1	0.039	0.075	-10000	0	-10000	0	0
Rac1/GDP	0.007	0.091	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.012	0.086	-10000	0	-0.52	1	1
CDC42/GDP	0.007	0.091	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
EFNA5	-0.043	0.08	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.003	0.004	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.022	0.11	-10000	0	-0.67	1	1
PTK2	0.016	0.026	-10000	0	-10000	0	0
MAP4K4	-0.042	0.14	-10000	0	-0.86	1	1
SRC	0	0	-10000	0	-10000	0	0
KALRN	0	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.005	0.084	-10000	0	-10000	0	0
MAP2K1	-0.012	0.071	-10000	0	-10000	0	0
WASL	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.048	0.15	-10000	0	-0.92	1	1
cell migration	0.04	0.088	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
SYNJ1	-0.017	0.022	-10000	0	-10000	0	0
PXN	0	0	-10000	0	-10000	0	0
TF	-0.72	0.3	-10000	0	-0.84	31	31
HRAS/GTP	-0.029	0.12	-10000	0	-0.74	1	1
Ephrin B1/EPHB1-2	-0.052	0.15	-10000	0	-0.92	1	1
cell adhesion mediated by integrin	-0.005	0.025	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
mol:GTP	-0.033	0.13	-10000	0	-0.81	1	1
RAC1-CDC42/GTP	-0.025	0.11	-10000	0	-0.69	1	1
RASA1	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.009	0.08	-10000	0	-10000	0	0
ruffle organization	-0.024	0.12	-10000	0	-0.7	1	1
NCK1	0	0	-10000	0	-10000	0	0
receptor internalization	0.003	0.05	-10000	0	-10000	0	0
Ephrin B/EPHB2/KALRN	0.018	0.024	-10000	0	-10000	0	0
ROCK1	-0.014	0.028	-10000	0	-10000	0	0
RAS family/GDP	-0.012	0.07	-10000	0	-10000	0	0
Rac1/GTP	-0.028	0.12	-10000	0	-0.74	1	1
Ephrin B/EPHB1/Src/Paxillin	-0.013	0.077	-10000	0	-0.47	1	1

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0	0	-9999	-10000	0	0
FYN	0	0	-9999	-10000	0	0
MAP3K12	0	0	-9999	-10000	0	0
FGR	0	0	-9999	-10000	0	0
p38 alpha/TAB1	0	0	-9999	-10000	0	0
PRKG1	0	0	-9999	-10000	0	0
DUSP8	0	0	-9999	-10000	0	0
PGK/cGMP/p38 alpha	0	0	-9999	-10000	0	0
apoptosis	0	0	-9999	-10000	0	0
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0	0	-9999	-10000	0	0
DUSP1	-0.036	0.22	-9999	-1.3	1	1
PAK1	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.063	0.007	-9999	-10000	0	0
BLK	-0.005	0.032	-9999	-10000	0	0
HCK	0	0	-9999	-10000	0	0
MAP2K3	0	0	-9999	-10000	0	0
DUSP16	0	0	-9999	-10000	0	0
DUSP10	0	0	-9999	-10000	0	0
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.059	0.005	-9999	-10000	0	0
positive regulation of innate immune response	0.074	0.007	-9999	-10000	0	0
LCK	-0.005	0.032	-9999	-10000	0	0
p38alpha-beta/MKP7	0	0	-9999	-10000	0	0
p38alpha-beta/MKP5	0	0	-9999	-10000	0	0
PGK/cGMP	0	0	-9999	-10000	0	0
PAK2	0	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.018	0.11	-9999	-0.66	1	1
CDC42	0	0	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
PAK3	0	0	-9999	-10000	0	0

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
STX1A	0	0.038	-9999	-9999
UniProt:P19321	0	0	-9999	-9999
RIMS1/UNC13B	-0.006	0.026	-9999	-9999
STXBP1	0	0	-9999	-9999
ACh/CHRNA1	-0.003	0.017	-9999	-9999
RAB3GAP2/RIMS1/UNC13B	-0.005	0.019	-9999	-9999
mol:Ca2+	0	0	-9999	-9999
UniProt:P30996	0	0	-9999	-9999
UniProt:Q60393	0	0	-9999	-9999
CST086	0	0	-9999	-9999
RIMS1	-0.011	0.044	-9999	-9999
mol:ACh	0.003	0.011	-9999	-9999
RAB3GAP2	0	0	-9999	-9999
STX1A/SNAP25/VAMP2	-0.003	0.016	-9999	-9999
UniProt:P10844	0	0	-9999	-9999
muscle contraction	-0.003	0.017	-9999	-9999
UNC13B	0	0	-9999	-9999
CHRNA1	-0.005	0.032	-9999	-9999
UniProt:P10845	0	0	-9999	-9999
ACh/Synaptotagmin 1	0	0.001	-9999	-9999
SNAP25	-0.007	0.015	-9999	-9999
VAMP2	0	0	-9999	-9999
SYT1	0	0	-9999	-9999
UniProt:Q00496	0	0	-9999	-9999
STXIA/STXBP1	-0.008	0.025	-9999	-9999
STX1A/SNAP25 fragment 1/VAMP2	-0.003	0.016	-9999	-9999

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
MDK	-0.037	0.076	-9999	-9999
GPC2	-0.016	0.053	-9999	-9999
GPC2/Midkine	-0.032	0.058	-9999	-9999
neuron projection morphogenesis	-0.032	0.058	-9999	-9999

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0	0	-9999	-10000	0	0
AKT1	0.067	0.14	-9999	-0.76	1	1
PTK2B	-0.031	0.19	-9999	-1.1	1	1
VEGFR2 homodimer/Frs2	-0.038	0.22	-9999	-1.4	1	1
CAV1	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.035	0.21	-9999	-1.3	1	1
endothelial cell proliferation	0.068	0.15	-9999	-0.71	1	1
mol:Ca2+	-0.031	0.18	-9999	-1.1	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.034	0.2	-9999	-1.2	1	1
RP11-342D11.1	0.018	0.19	-9999	-1.1	1	1
CDH5	0	0	-9999	-10000	0	0
VEGFA homodimer	0	0	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
SHC2	0	0	-9999	-10000	0	0
HRAS/GDP	-0.026	0.15	-9999	-0.92	1	1
SH2D2A	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.022	0.13	-9999	-0.8	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.035	0.21	-9999	-1.3	1	1
VEGFR1 homodimer	0	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.03	0.18	-9999	-1.1	1	1
GRB10	-0.031	0.18	-9999	-1.1	1	1
PTPN11	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
PAK1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.033	0.19	-9999	-1.2	1	1
HRAS	0	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.012	0.072	-9999	-0.44	1	1
HIF1A	0	0	-9999	-10000	0	0
FRS2	0	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.033	0.19	-9999	-1.2	1	1
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0	0	-9999	-10000	0	0
Nck/Pak	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.035	0.21	-9999	-1.3	1	1
mol:GDP	-0.028	0.17	-9999	-1	1	1
mol:NADP	0.06	0.12	-9999	-0.63	1	1
eNOS/Hsp90	0.062	0.11	-9999	-0.58	1	1
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	-0.032	0.19	-9999	-1.1	1	1
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0	0	-9999	-10000	0	0
VEGFA	0	0	-9999	-10000	0	0
VEGFC	0	0	-9999	-10000	0	0
FAK1/Vinculin	-0.029	0.17	-9999	-1	1	1
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.034	0.2	-9999	-1.2	1	1
PTPN6	0	0	-9999	-10000	0	0
EPAS1	-0.012	0.07	-9999	-10000	0	0
mol:L-citrulline	0.06	0.12	-9999	-0.63	1	1
ITGAV	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.034	0.2	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer	-0.035	0.21	-9999	-1.3	1	1
VEGFR2/3 heterodimer	-0.038	0.22	-9999	-1.4	1	1
VEGFB	0	0	-9999	-10000	0	0
MAPK11	0.03	0.2	-9999	-1.2	1	1
VEGFR2 homodimer	-0.006	0.25	-9999	-1.5	1	1
FLT1	0	0	-9999	-10000	0	0
NEDD4	0	0	-9999	-10000	0	0
MAPK3	0.031	0.18	-9999	-0.99	1	1
MAPK1	0.031	0.18	-9999	-0.99	1	1
VEGFA145/NRP2	0	0	-9999	-10000	0	0
VEGFR1/2 heterodimer	-0.038	0.22	-9999	-1.4	1	1
KDR	-0.007	0.25	-9999	-1.5	1	1
VEGFA165/NRP1/VEGFR2 homodimer	-0.033	0.19	-9999	-1.2	1	1
SRC	0	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.032	0.18	-9999	-1	1	1
PI3K	-0.029	0.17	-9999	-1	1	1
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.035	0.21	-9999	-1.3	1	1
FES	-0.033	0.2	-9999	-1.2	1	1
GAB1	-0.03	0.18	-9999	-1.1	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	-0.035	0.21	-9999	-1.3	1	1
CTNNB1	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.062	0.11	-9999	-0.58	1	1
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.035	0.21	-9999	-1.3	1	1
PI3K/GAB1	-0.022	0.13	-9999	-0.78	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.033	0.19	-9999	-1.2	1	1
PRKACA	0	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.036	0.21	-9999	-1.3	1	1
HSP90AA1	0	0	-9999	-10000	0	0
CDC42	-0.033	0.2	-9999	-1.2	1	1
actin cytoskeleton reorganization	-0.035	0.2	-9999	-1.2	1	1
PTK2	0.037	0.2	-9999	-1.2	1	1
EDG1	0.018	0.19	-9999	-1.1	1	1
mol:DAG	-0.032	0.19	-9999	-1.1	1	1
CaM/Ca2+	-0.029	0.17	-9999	-1	1	1
MAP2K3	0.034	0.19	-9999	-1.1	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.034	0.2	-9999	-1.2	1	1
PLCG1	-0.033	0.2	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.034	0.2	-9999	-1.2	1	1
IQGAP1	0	0	-9999	-10000	0	0
YES1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.035	0.21	-9999	-1.3	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.035	0.21	-9999	-1.3	1	1
cell migration	0.07	0.15	-9999	-0.8	1	1
mol:PI-3-4-5-P3	-0.025	0.15	-9999	-0.9	1	1
FYN	0	0	-9999	-10000	0	0
VEGFB/NRP1	-0.029	0.17	-9999	-1	1	1
mol:NO	0.06	0.12	-9999	-0.63	1	1
PXN	0	0	-9999	-10000	0	0
HRAS/GTP	-0.026	0.15	-9999	-0.93	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.034	0.2	-9999	-1.2	1	1
VHL	0	0	-9999	-10000	0	0
ITGB3	0	0	-9999	-10000	0	0
NOS3	0.059	0.14	-9999	-0.75	1	1
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.035	0.21	-9999	-1.3	1	1
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.035	0.18	-9999	-1	1	1
PRKCB	0.008	0.23	-9999	-0.93	2	2
VCL	0	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.031	0.18	-9999	-1.1	1	1
VEGFR1/2 heterodimer/VEGFA homodimer	-0.035	0.21	-9999	-1.3	1	1
VEGFA165/NRP2	0	0	-9999	-10000	0	0
MAPKKK cascade	-0.026	0.15	-9999	-0.94	1	1
NRP2	0	0	-9999	-10000	0	0
VEGFC homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
ROCK1	0	0	-9999	-10000	0	0
FAK1/Paxillin	-0.029	0.17	-9999	-1	1	1
MAP3K13	-0.033	0.2	-9999	-1.2	1	1
PDPK1	0.06	0.14	-9999	-0.75	1	1

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0	0	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
EGFR	-0.073	0.3	-9999	-1.3	2	2
AKT	0.04	0.01	-9999	-10000	0	0
FOXO3	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
FOXO1	0	0	-9999	-10000	0	0
AKT3	0	0	-9999	-10000	0	0
FOXO4	0	0	-9999	-10000	0	0
MET	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
PIK3CB	0	0	-9999	-10000	0	0
NRAS	0	0	-9999	-10000	0	0
PIK3CG	0	0	-9999	-10000	0	0
PIK3R3	0	0	-9999	-10000	0	0
PIK3R2	0	0	-9999	-10000	0	0
NF1	0	0	-9999	-10000	0	0
RAS	0.014	0.056	-9999	-10000	0	0
ERBB2	0	0	-9999	-10000	0	0
proliferation/survival/translation	-0.031	0.005	-9999	-10000	0	0
PI3K	0.024	0.055	-9999	-0.2	2	2
PIK3R1	0	0	-9999	-10000	0	0
KRAS	0	0	-9999	-10000	0	0
FOXO	0.046	0.011	-9999	-10000	0	0
AKT2	0	0	-9999	-10000	0	0
PTEN	0	0	-9999	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.008	0.048	-9999	-10000	0	0
NFATC2	0.003	0.28	-9999	-1.1	2	2
NFATC3	0.01	0.034	-9999	-10000	0	0
CD40LG	0.013	0.34	-9999	-1.1	2	2
ITCH	0.038	0.062	-9999	-10000	0	0
CBLB	0.038	0.062	-9999	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.061	0.24	-9999	-1.2	1	1
JUNB	0	0	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.011	0.066	-9999	-10000	0	0
T cell anergy	-0.001	0.098	-9999	-0.51	1	1
TLE4	0.029	0.22	-9999	-0.88	2	2
Jun/NFAT1-c-4/p21SNFT	-0.025	0.16	-9999	-10000	0	0
AP-1/NFAT1-c-4	-0.1	0.35	-9999	-1.3	2	2
IKZF1	0.029	0.22	-9999	-0.88	2	2
T-helper 2 cell differentiation	0.023	0.2	-9999	-0.77	2	2
AP-1/NFAT1	-0.12	0.36	-9999	-1.1	4	4
CALM1	-0.006	0.034	-9999	-10000	0	0
EGR2	0.087	0.13	-9999	-10000	0	0
EGR3	0.087	0.13	-9999	-10000	0	0
NFAT1/FOXP3	-0.06	0.2	-9999	-0.88	2	2
EGR1	-0.036	0.21	-9999	-1.3	1	1
JUN	0	0.009	-9999	-10000	0	0
EGR4	-0.021	0.059	-9999	-10000	0	0
mol:Ca2+	-0.006	0.038	-9999	-10000	0	0
GBP3	-0.006	0.32	-9999	-1.1	3	3
FOSL1	-0.011	0.044	-9999	-10000	0	0
NFAT1-c-4/MAF/IRF4	-0.041	0.15	-9999	-10000	0	0
DGKA	0.026	0.22	-9999	-0.88	2	2
CREM	0	0	-9999	-10000	0	0
NFAT1-c-4/PPARG	-0.067	0.22	-9999	-0.98	1	1
CTLA4	0.025	0.2	-9999	-0.76	2	2
NFAT1-c-4 (dimer)/EGR1	-0.061	0.2	-9999	-10000	0	0
NFAT1-c-4 (dimer)/EGR4	-0.023	0.17	-9999	-10000	0	0
FOS	-0.11	0.37	-9999	-1.3	3	3
IFNG	-0.054	0.22	-9999	-0.86	2	2
T cell activation	0.03	0.2	-9999	-0.73	2	2
MAF	0	0	-9999	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-9999	-10000	0	0
activation-induced cell death of T cells	-0.077	0.085	-9999	-10000	0	0
TNF	0.053	0.2	-9999	-10000	0	0
FASLG	0.084	0.14	-9999	-10000	0	0
TBX21	-0.024	0.22	-9999	-1.3	1	1
BATF3	0	0	-9999	-10000	0	0
PRKCQ	-0.022	0.22	-9999	-1.3	1	1
PTPN1	0.029	0.22	-9999	-0.88	2	2
NFAT1-c-4/ICER1	-0.042	0.16	-9999	-10000	0	0
GATA3	-0.005	0.032	-9999	-10000	0	0
T-helper 1 cell differentiation	-0.05	0.22	-9999	-0.84	2	2
IL2RA	-0.06	0.23	-9999	-0.9	2	2
T-helper 1 cell lineage commitment	0	0	-9999	-10000	0	0
CASP3	0.029	0.22	-9999	-0.88	2	2
E2F1	-0.058	0.098	-9999	-10000	0	0
PPARG	-0.036	0.22	-9999	-1.3	1	1
SLC3A2	0.029	0.22	-9999	-0.88	2	2
IRF4	-0.005	0.032	-9999	-10000	0	0
PTGS2	0.001	0.39	-9999	-1.3	2	2
CSF2	0.013	0.34	-9999	-1.1	2	2
JunB/Fra1/NFAT1-c-4	-0.031	0.15	-9999	-10000	0	0
IL4	0.021	0.2	-9999	-0.81	2	2
IL5	0.014	0.34	-9999	-1.1	2	2
IL2	0.03	0.21	-9999	-0.84	1	1
IL3	-0.018	0.044	-9999	-10000	0	0
RNF128	-0.006	0.23	-9999	-1.3	1	1
NFATC1	0.078	0.085	-9999	-10000	0	0
CDK4	-0.068	0.11	-9999	-10000	0	0
PTPRK	0.029	0.22	-9999	-0.88	2	2
IL8	-0.004	0.38	-9999	-1.1	3	3
POU2F1	0	0	-9999	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0	0	-9999	-10000	0	0
epithelial cell differentiation	0	0	-9999	-10000	0	0
CYFIP2	0	0	-9999	-10000	0	0
ENAH	0.07	0	-9999	-10000	0	0
EGFR	-0.073	0.3	-9999	-1.3	2	2
EPHA2	0	0	-9999	-10000	0	0
MYO6	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	0	0	-9999	-10000	0	0
AQP5	0.013	0.021	-9999	-10000	0	0
CTNND1	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.011	0.022	-9999	-10000	0	0
EGF	-0.016	0.053	-9999	-10000	0	0
NCKAP1	0	0	-9999	-10000	0	0
AQP3	0	0	-9999	-10000	0	0
cortical microtubule organization	0	0	-9999	-10000	0	0
GO:0000145	0.038	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
MLLT4	0	0	-9999	-10000	0	0
ARF6/GDP	0	0	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.051	0	-9999	-10000	0	0
PVRL2	0	0	-9999	-10000	0	0
ZYX	0	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
CDH1	0	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.049	0.2	-9999	-0.85	2	2
RhoA/GDP	0	0	-9999	-10000	0	0
actin cytoskeleton organization	0.046	0	-9999	-10000	0	0
IGF-1R heterotetramer	-0.005	0.032	-9999	-10000	0	0
GIT1	0	0	-9999	-10000	0	0
IGF1R	-0.005	0.032	-9999	-10000	0	0
IGF1	-0.69	0.65	-9999	-1.3	19	19
DIAPH1	0	0	-9999	-10000	0	0
Wnt receptor signaling pathway	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
VCL	0	0	-9999	-10000	0	0
EFNA1	0	0	-9999	-10000	0	0
LPP	0.047	0	-9999	-10000	0	0
Ephrin A1/EPHA2	0	0	-9999	-10000	0	0
SEC6/SEC8	0	0	-9999	-10000	0	0
MGAT3	0.011	0.022	-9999	-10000	0	0
HGF/MET	-0.14	0.3	-9999	-0.81	6	6
HGF	-0.22	0.49	-9999	-1.3	6	6
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0	0	-9999	-10000	0	0
actin cable formation	0.086	0	-9999	-10000	0	0
KIAA1543	0.047	0	-9999	-10000	0	0
KIFC3	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
EXOC3	0	0	-9999	-10000	0	0
ACTN1	0	0	-9999	-10000	0	0
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
EXOC4	0	0	-9999	-10000	0	0
STX4	0	0	-9999	-10000	0	0
PIP5K1C	0	0	-9999	-10000	0	0
LIMA1	0	0	-9999	-10000	0	0
ABI1	0	0	-9999	-10000	0	0
ROCK1	0	0	-9999	-10000	0	0
adherens junction assembly	0.063	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.43	0.4	-9999	-0.81	19	19
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	0	0	-9999	-10000	0	0
PLEKHA7	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
establishment of epithelial cell apical/basal polarity	0	0	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0	0	-9999	-10000	0	0
regulation of cell-cell adhesion	0.046	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0	0	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0	0	-9999	-10000	0	0
KLHL20	-0.007	0.039	-9999	-10000	0	0
CYFIP2	0	0	-9999	-10000	0	0
Rac1/GDP	0.063	0.008	-9999	-10000	0	0
ENAH	0	0	-9999	-10000	0	0
AP1M1	0	0	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	0	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.004	0.026	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.025	0.15	-9999	-0.92	1	1
RAPGEF1	0.056	0	-9999	-10000	0	0
CTNND1	0	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0	-9999	-10000	0	0
CRK	0.049	0	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	0	0	-9999	-10000	0	0
alphaE/beta7 Integrin	-0.03	0.18	-9999	-1.1	1	1
IQGAP1	0	0	-9999	-10000	0	0
NCKAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	0	0	-9999	-10000	0	0
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
MLLT4	0	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.026	0.15	-9999	-0.92	1	1
PI3K	0	0	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0	0	-9999	-10000	0	0
TIAM1	-0.036	0.22	-9999	-1.3	1	1
E-cadherin(dimer)/Ca2+	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
CDH1	0	0	-9999	-10000	0	0
RhoA/GDP	0.062	0.008	-9999	-10000	0	0
actin cytoskeleton organization	-0.005	0.029	-9999	-10000	0	0
CDC42/GDP	0.062	0.008	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
ITGB7	-0.036	0.22	-9999	-1.3	1	1
RAC1	0	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	0	0	-9999	-10000	0	0
mol:GDP	0.062	0.008	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0	0	-9999	-10000	0	0
p120 catenin/RhoA/GDP	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.003	0.018	-9999	-10000	0	0
NME1	0	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0	0	-9999	-10000	0	0
regulation of cell-cell adhesion	0	0	-9999	-10000	0	0
WASF2	-0.002	0.013	-9999	-10000	0	0
Rap1/GTP	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.024	0.14	-9999	-0.87	1	1
CCND1	-0.004	0.021	-9999	-10000	0	0
VAV2	0.052	0	-9999	-10000	0	0
RAP1/GDP	0	0	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0	0	-9999	-10000	0	0
PIP5K1C	0	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.023	0.14	-9999	-0.84	1	1
E-cadherin/beta catenin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
Rac1/GTP	-0.011	0.065	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	0	0	-9999	-10000	0	0
ITGAE	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	-9999	-9999
MDM2/SUMO1	-9999	-9999
HDAC4	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	-9999	-9999
SUMO1	-9999	-9999
NPC/RanGAP1/SUMO1	-9999	-9999
mol:GTP	-9999	-9999
XPO1	-9999	-9999
EntrezGene:23636	-9999	-9999
RAN	-9999	-9999
EntrezGene:8021	-9999	-9999
RANBP2	-9999	-9999
SUMO1/HDAC4	-9999	-9999
SUMO1/HDAC1	-9999	-9999
RANGAP1	-9999	-9999
MDM2/SUMO1/SUMO1	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	-9999	-9999
Ran/GTP	-9999	-9999
EntrezGene:23225	-9999	-9999
MDM2	-9999	-9999
UBE2I	-9999	-9999
Ran/GTP/Exportin 1	-9999	-9999
NPC	-9999	-9999
PIAS2	-9999	-9999
PIAS1	-9999	-9999
EntrezGene:9972	-9999	-9999

×

IL2 signaling events mediated by STAT5

Figure S111. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S111. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
GAB2	0	0	-9999	-9999
ELF1	-0.005	0.017	-9999	-9999
CCNA2	-0.027	0.067	-9999	-9999
PIK3CA	0	0	-9999	-9999
JAK3	-0.005	0.032	-9999	-9999
PIK3R1	0	0	-9999	-9999
JAK1	0	0	-9999	-9999
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.002	0.012	-9999	-9999
SHC1	0	0	-9999	-9999
SP1	-0.011	0.024	-9999	-9999
IL2RA	0.017	0.042	-9999	-9999
IL2RB	0	0	-9999	-9999
SOS1	0	0	-9999	-9999
IL2RG	-0.005	0.032	-9999	-9999
G1/S transition of mitotic cell cycle	0.03	0.028	-9999	-9999
PTPN11	0	0	-9999	-9999
CCND2	0.004	0.057	-9999	-9999
LCK	-0.005	0.032	-9999	-9999
GRB2	0	0	-9999	-9999
IL2	0	0.001	-9999	-9999
CDK6	0	0	-9999	-9999
CCND3	0.074	0.026	-9999	-9999

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0	0	-9999	-10000	0	0
DAPP1	0.046	0.018	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK	0.059	0.031	-9999	-10000	0	0
mol:DAG	0.057	0.044	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
ARF5/GDP	-0.006	0.033	-9999	-10000	0	0
PLCG2	0	0	-9999	-10000	0	0
PLCG1	0	0	-9999	-10000	0	0
ARF5	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
YES1	0	0	-9999	-10000	0	0
RAP1A/GTP	0	0	-9999	-10000	0	0
ADAP1	0	0	-9999	-10000	0	0
ARAP3	0	0	-9999	-10000	0	0
INPPL1	0	0	-9999	-10000	0	0
PREX1	0	0	-9999	-10000	0	0
ARHGEF6	0	0	-9999	-10000	0	0
ARHGEF7	0	0	-9999	-10000	0	0
ARF1	0	0	-9999	-10000	0	0
NRAS	0	0	-9999	-10000	0	0
FYN	0	0	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
FGR	0	0	-9999	-10000	0	0
mol:Ca2+	0.043	0.026	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	-0.036	0.22	-9999	-1.3	1	1
ZAP70	-0.005	0.032	-9999	-10000	0	0
mol:IP3	0.052	0.034	-9999	-10000	0	0
LYN	0	0	-9999	-10000	0	0
ARF1/GDP	-0.006	0.033	-9999	-10000	0	0
RhoA/GDP	-0.002	0.014	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
BLNK	0	0	-9999	-10000	0	0
actin cytoskeleton reorganization	0.061	0.037	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
PLEKHA2	0.028	0.018	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
PTEN	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.002	0.016	-9999	-10000	0	0
BLK	-0.005	0.032	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
CYTH1	0	0	-9999	-10000	0	0
HCK	0	0	-9999	-10000	0	0
CYTH3	0	0	-9999	-10000	0	0
CYTH2	0	0	-9999	-10000	0	0
KRAS	0	0	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	0	0	-9999	-10000	0	0
SGK1	0	0	-9999	-10000	0	0
INPP5D	-0.005	0.032	-9999	-10000	0	0
mol:GDP	0.032	0.042	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
SYK	-0.005	0.032	-9999	-10000	0	0
ARF6/GDP	-0.002	0.014	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
ARAP3/RAP1A/GTP	0	0	-9999	-10000	0	0
VAV1	-0.005	0.032	-9999	-10000	0	0
mol:PI-3-4-P2	0.019	0.022	-9999	-10000	0	0
RAS family/GTP/PI3K Class I	0	0	-9999	-10000	0	0
PLEKHA1	0.028	0.018	-9999	-10000	0	0
Rac1/GDP	-0.006	0.033	-9999	-10000	0	0
LAT	-0.011	0.044	-9999	-10000	0	0
Rac1/GTP	-0.012	0.072	-9999	-0.44	1	1
ITK	-0.046	0.19	-9999	-0.82	2	2
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.066	0.056	-9999	-10000	0	0
LCK	-0.005	0.032	-9999	-10000	0	0
BTK	-0.001	0.007	-9999	-10000	0	0

×

Arf6 trafficking events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.073	0.3	-9999	-1.3	2	2
CLTC	0.031	0	-9999	-10000	0	0
calcium ion-dependent exocytosis	0	0	-9999	-10000	0	0
Dynamin 2/GTP	0	0	-9999	-10000	0	0
EXOC4	0	0	-9999	-10000	0	0
CD59	0.029	0	-9999	-10000	0	0
CPE	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
membrane fusion	0	0	-9999	-10000	0	0
CTNND1	0	0	-9999	-10000	0	0
DNM2	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.033	0	-9999	-10000	0	0
TSHR	0.002	0.004	-9999	-10000	0	0
INS	0.013	0.003	-9999	-10000	0	0
BIN1	0	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
membrane depolarization	0	0	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
JUP	0.029	0	-9999	-10000	0	0
ASAP2/amphiphysin II	0	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
CDH1	0.029	0	-9999	-10000	0	0
clathrin-independent pinocytosis	0	0	-9999	-10000	0	0
MAPK8IP3	0	0	-9999	-10000	0	0
positive regulation of endocytosis	0	0	-9999	-10000	0	0
EXOC2	0	0	-9999	-10000	0	0
substrate adhesion-dependent cell spreading	0	0	-9999	-10000	0	0
insulin receptor binding	0	0	-9999	-10000	0	0
SPAG9	0	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0	-9999	-10000	0	0
positive regulation of phagocytosis	0	0	-9999	-10000	0	0
ARF6/GTP/JIP3	0	0	-9999	-10000	0	0
ACAP1	0.001	0.005	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CHRM2	0.025	0.003	-9999	-10000	0	0
clathrin heavy chain/ACAP1	0.038	0	-9999	-10000	0	0
JIP4/KLC1	0	0	-9999	-10000	0	0
EXOC1	0	0	-9999	-10000	0	0
exocyst	0	0	-9999	-10000	0	0
RALA/GTP	0	0	-9999	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-9999	-10000	0	0
receptor recycling	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
NME1	0	0	-9999	-10000	0	0
clathrin coat assembly	0.031	0	-9999	-10000	0	0
IL2RA	0.025	0.012	-9999	-10000	0	0
VAMP3	0	0	-9999	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.043	0.18	-9999	-0.77	2	2
EXOC6	0	0	-9999	-10000	0	0
PLD1	0	0	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
EXOC5	0	0	-9999	-10000	0	0
PIP5K1C	0.033	0	-9999	-10000	0	0
SDC1	0.017	0.068	-9999	-10000	0	0
ARF6/GDP	0	0	-9999	-10000	0	0
EXOC7	0	0	-9999	-10000	0	0
E-cadherin/beta catenin	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
endocytosis	0	0	-9999	-10000	0	0
SCAMP2	0	0	-9999	-10000	0	0
ADRB2	-0.37	0.44	-9999	-0.84	17	17
EXOC3	0	0	-9999	-10000	0	0
ASAP2	0	0	-9999	-10000	0	0
Dynamin 2/GDP	0	0	-9999	-10000	0	0
KLC1	0	0	-9999	-10000	0	0
AVPR2	0.033	0.02	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
CDKN2B	0.004	0.008	-9999	-9999
CDKN2C	0.008	0.012	-9999	-9999
CDKN2A	-0.037	0.081	-9999	-9999
CCND2	-0.002	0.016	-9999	-9999
RB1	0.001	0.016	-9999	-9999
CDK4	0	0.017	-9999	-9999
CDK6	0	0.015	-9999	-9999
G1/S progression	-0.001	0.016	-9999	-9999

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.003	0.074	-9999	-10000	0	0
RAD9A	0	0	-9999	-10000	0	0
AP1	-0.09	0.3	-9999	-1.1	3	3
IFNAR2	0.009	0.006	-9999	-10000	0	0
AKT1	-0.27	0.19	-9999	-0.4	25	25
ER alpha/Oestrogen	-0.76	0.5	-9999	-1.1	25	25
NFX1/SIN3/HDAC complex	0	0	-9999	-10000	0	0
EGF	-0.016	0.053	-9999	-10000	0	0
SMG5	0	0	-9999	-10000	0	0
SMG6	0	0	-9999	-10000	0	0
SP3/HDAC2	0	0	-9999	-10000	0	0
TERT/c-Abl	-0.021	0.052	-9999	-10000	0	0
SAP18	0	0	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	0.007	0.006	-9999	-10000	0	0
WRN	0	0	-9999	-10000	0	0
SP1	0.011	0.006	-9999	-10000	0	0
SP3	0	0	-9999	-10000	0	0
TERF2IP	0	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.016	0.043	-9999	-10000	0	0
Mad/Max	0	0	-9999	-10000	0	0
TERT	-0.004	0.074	-9999	-10000	0	0
CCND1	0.006	0.069	-9999	-10000	0	0
MAX	0	0	-9999	-10000	0	0
RBBP7	0	0	-9999	-10000	0	0
RBBP4	0	0	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
Telomerase/911	0	0.001	-9999	-10000	0	0
CDKN1B	0.034	0.011	-9999	-10000	0	0
RAD1	0	0	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
SAP30	0	0	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0	0	-9999	-10000	0	0
JUN	0	0	-9999	-10000	0	0
E6	0.001	0.001	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0	-9999	-10000	0	0
FOS	-0.11	0.36	-9999	-1.3	3	3
IFN-gamma/IRF1	0	0	-9999	-10000	0	0
PARP2	0	0	-9999	-10000	0	0
BLM	-0.005	0.032	-9999	-10000	0	0
Telomerase	-0.002	0.006	-9999	-10000	0	0
IRF1	0	0	-9999	-10000	0	0
ESR1	-0.91	0.6	-9999	-1.3	25	25
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0	0	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC2	0.01	0.006	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.021	0.001	-9999	-10000	0	0
ABL1	0	0	-9999	-10000	0	0
MXD1	0	0	-9999	-10000	0	0
MRE11A	0	0	-9999	-10000	0	0
HUS1	0	0	-9999	-10000	0	0
RPS6KB1	0	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.14	0.098	-9999	-10000	0	0
NR2F2	0.001	0.004	-9999	-10000	0	0
MAPK3	0.016	0.007	-9999	-10000	0	0
MAPK1	0.016	0.007	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
HNRNPC	0	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0	0	-9999	-10000	0	0
EGFR	-0.073	0.3	-9999	-1.3	2	2
mol:Oestrogen	0	0	-9999	-10000	0	0
EGF/EGFR	-0.069	0.26	-9999	-1.1	2	2
MYC	0	0	-9999	-10000	0	0
IL2	0.006	0.006	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
TGFB1	0	0	-9999	-10000	0	0
TRF2/BLM	-0.003	0.016	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.019	0.05	-9999	-10000	0	0
SP1/HDAC2	0	0	-9999	-10000	0	0
PINX1	0	0	-9999	-10000	0	0
Telomerase/EST1A	-0.016	0.043	-9999	-10000	0	0
Smad3/Myc	0	0	-9999	-10000	0	0
911 complex	0	0	-9999	-10000	0	0
IFNG	0.001	0.002	-9999	-10000	0	0
Telomerase/PinX1	-0.016	0.043	-9999	-10000	0	0
Telomerase/AKT1/mTOR/p70S6K	-0.056	0.071	-9999	-10000	0	0
SIN3B	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
Telomerase/EST1B	-0.016	0.043	-9999	-10000	0	0
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.016	0.043	-9999	-10000	0	0
E2F1	-0.064	0.096	-9999	-10000	0	0
ZNFX1	0	0	-9999	-10000	0	0
PIF1	-0.005	0.032	-9999	-10000	0	0
NCL	0	0	-9999	-10000	0	0
DKC1	0	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

BCR signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.014	0.11	-9999	-0.49	1	1
IKBKB	0.017	0.045	-9999	-10000	0	0
AKT1	0.018	0.079	-9999	-0.3	1	1
IKBKG	0.019	0.046	-9999	-10000	0	0
CALM1	0.002	0.063	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
MAP3K1	0.005	0.17	-9999	-0.87	1	1
MAP3K7	0	0	-9999	-10000	0	0
mol:Ca2+	-0.014	0.064	-9999	-10000	0	0
DOK1	0	0	-9999	-10000	0	0
AP-1	0.001	0.099	-9999	-0.27	3	3
LYN	0	0	-9999	-10000	0	0
BLNK	0	0	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
BCR complex	-0.07	0.25	-9999	-1.1	2	2
CD22	-0.063	0.25	-9999	-1	2	2
CAMK2G	0.01	0.06	-9999	-10000	0	0
CSNK2A1	0	0	-9999	-10000	0	0
INPP5D	-0.005	0.032	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.048	0.18	-9999	-10000	0	0
GO:0007205	-0.006	0.067	-9999	-10000	0	0
SYK	-0.005	0.032	-9999	-10000	0	0
ELK1	0.002	0.064	-9999	-10000	0	0
NFATC1	0	0.13	-9999	-0.63	1	1
B-cell antigen/BCR complex	-0.07	0.25	-9999	-1.1	2	2
PAG1/CSK	0	0	-9999	-10000	0	0
NFKBIB	0.015	0.017	-9999	-10000	0	0
HRAS	0.005	0.078	-9999	-10000	0	0
NFKBIA	0.015	0.017	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.019	0.015	-9999	-10000	0	0
RasGAP/Csk	-0.071	0.29	-9999	-1.2	2	2
mol:GDP	-0.006	0.059	-9999	-10000	0	0
PTEN	0	0	-9999	-10000	0	0
CD79B	-0.005	0.032	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	0.019	0.014	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
PI3K/BCAP/CD19	-0.003	0.16	-9999	-0.63	2	2
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	-0.016	0.065	-9999	-10000	0	0
CSK	0	0	-9999	-10000	0	0
FOS	-0.057	0.23	-9999	-0.78	3	3
CHUK	0.019	0.046	-9999	-10000	0	0
IBTK	0	0	-9999	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.021	0.049	-9999	-10000	0	0
PTPN6	-0.056	0.22	-9999	-1.3	1	1
RELA	0	0	-9999	-10000	0	0
BCL2A1	0.014	0.036	-9999	-0.19	1	1
VAV2	-0.06	0.22	-9999	-0.92	2	2
ubiquitin-dependent protein catabolic process	0.019	0.017	-9999	-10000	0	0
BTK	0.003	0.028	-9999	-10000	0	0
CD19	-0.07	0.25	-9999	-1	2	2
MAP4K1	-0.005	0.032	-9999	-10000	0	0
CD72	-0.005	0.032	-9999	-10000	0	0
PAG1	0	0	-9999	-10000	0	0
MAPK14	0.017	0.14	-9999	-0.68	1	1
SH3BP5	0	0	-9999	-10000	0	0
PIK3AP1	0.005	0.067	-9999	-10000	0	0
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.033	0.13	-9999	-0.57	2	2
RAF1	0.013	0.074	-9999	-10000	0	0
RasGAP/p62DOK/SHIP	-0.07	0.28	-9999	-1.2	2	2
CD79A	-0.083	0.3	-9999	-1.3	2	2
re-entry into mitotic cell cycle	0.001	0.097	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
MAPK3	0.027	0.064	-9999	-10000	0	0
MAPK1	0.027	0.064	-9999	-10000	0	0
CD72/SHP1	-0.051	0.2	-9999	-1.1	1	1
NFKB1	0	0	-9999	-10000	0	0
MAPK8	-0.003	0.18	-9999	-0.67	2	2
actin cytoskeleton organization	-0.009	0.18	-9999	-0.91	1	1
NF-kappa-B/RelA	0.041	0.029	-9999	-10000	0	0
Calcineurin	-0.011	0.047	-9999	-10000	0	0
PI3K	-0.045	0.15	-9999	-0.76	1	1
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.017	0.066	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
Bam32/HPK1	-0.043	0.18	-9999	-1	1	1
DAPP1	-0.045	0.22	-9999	-1.3	1	1
cytokine secretion	0.002	0.12	-9999	-0.58	1	1
mol:DAG	-0.016	0.065	-9999	-10000	0	0
PLCG2	0	0	-9999	-10000	0	0
MAP2K1	0.02	0.07	-9999	-10000	0	0
B-cell antigen/BCR complex/FcgammaRIIB	-0.085	0.34	-9999	-1.4	2	2
mol:PI-3-4-5-P3	-0.03	0.1	-9999	-0.47	1	1
ETS1	0.018	0.056	-9999	-10000	0	0
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.053	0.2	-9999	-0.87	2	2
B-cell antigen/BCR complex/LYN	-0.064	0.28	-9999	-1.1	2	2
MALT1	0	0	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
RAC1	-0.014	0.2	-9999	-1	1	1
B-cell antigen/BCR complex/LYN/SYK	-0.065	0.25	-9999	-1.1	2	2
CARD11	-0.017	0.069	-9999	-10000	0	0
FCGR2B	-0.036	0.22	-9999	-1.3	1	1
PPP3CA	0	0	-9999	-10000	0	0
BCL10	0	0	-9999	-10000	0	0
IKK complex	0.019	0.024	-9999	-10000	0	0
PTPRC	-0.036	0.22	-9999	-1.3	1	1
PDPK1	-0.02	0.064	-9999	-10000	0	0
PPP3CB	0	0	-9999	-10000	0	0
PPP3CC	0	0	-9999	-10000	0	0
POU2F2	0.018	0.013	-9999	-10000	0	0

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0	0	-9999	-10000	0	0
EGFR	-0.073	0.3	-9999	-1.3	2	2
EGF/EGFR	-0.053	0.2	-9999	-0.89	2	2
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.048	0.21	-9999	-0.91	2	2
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.016	0.053	-9999	-10000	0	0
EGF/EGFR dimer/SHC	-0.061	0.23	-9999	-1	2	2
mol:GDP	-0.052	0.2	-9999	-0.89	2	2
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0	0	-9999	-10000	0	0
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.048	0.19	-9999	-0.83	2	2
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.044	0.19	-9999	-0.84	2	2
FRAP1	-0.051	0.2	-9999	-0.86	2	2
EGF/EGFR dimer	-0.069	0.26	-9999	-1.1	2	2
SOS1	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	0	0	-9999	-10000	0	0

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	0.12	0.15	-9999	-10000	0	0
IL23A	0.13	0.15	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.027	0.077	-9999	-10000	0	0
positive regulation of T cell mediated cytotoxicity	0.13	0.16	-9999	-10000	0	0
ITGA3	0.11	0.15	-9999	-10000	0	0
IL17F	0.12	0.12	-9999	-10000	0	0
IL12B	0.029	0.023	-9999	-10000	0	0
STAT1 (dimer)	-0.015	0.095	-9999	-10000	0	0
CD4	0.092	0.29	-9999	-1.4	1	1
IL23	0.045	0.15	-9999	-10000	0	0
IL23R	0.057	0.051	-9999	-10000	0	0
IL1B	0.12	0.15	-9999	-10000	0	0
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	0.12	0.15	-9999	-10000	0	0
TYK2	0.024	0.012	-9999	-10000	0	0
STAT4	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
IL18RAP	0	0	-9999	-10000	0	0
IL12RB1	0.019	0.035	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
IL12Rbeta1/TYK2	0.01	0.028	-9999	-10000	0	0
IL23R/JAK2	0.076	0.062	-9999	-10000	0	0
positive regulation of chronic inflammatory response	0.13	0.16	-9999	-10000	0	0
natural killer cell activation	-0.005	0.004	-9999	-10000	0	0
JAK2	0.034	0.016	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	0.074	0.15	-9999	-10000	0	0
ALOX12B	0.12	0.15	-9999	-10000	0	0
CXCL1	0.088	0.29	-9999	-1.5	1	1
T cell proliferation	0.13	0.16	-9999	-10000	0	0
NFKBIA	0	0	-9999	-10000	0	0
IL17A	0.12	0.11	-9999	-10000	0	0
PI3K	-0.028	0.079	-9999	-10000	0	0
IFNG	0.011	0.017	-9999	-10000	0	0
STAT3 (dimer)	-0.026	0.074	-9999	-10000	0	0
IL18R1	-0.036	0.22	-9999	-1.3	1	1
IL23/IL23R/JAK2/TYK2/SOCS3	0.1	0.12	-9999	-10000	0	0
IL18/IL18R	-0.045	0.18	-9999	-1.1	1	1
macrophage activation	-0.001	0.007	-9999	-10000	0	0
TNF	0.12	0.15	-9999	-10000	0	0
STAT3/STAT4	-0.028	0.079	-9999	-10000	0	0
STAT4 (dimer)	-0.015	0.095	-9999	-10000	0	0
IL18	-0.043	0.08	-9999	-10000	0	0
IL19	0.12	0.15	-9999	-10000	0	0
STAT5A (dimer)	-0.015	0.095	-9999	-10000	0	0
STAT1	0	0	-9999	-10000	0	0
SOCS3	-0.036	0.22	-9999	-1.3	1	1
CXCL9	0.059	0.38	-9999	-1.4	2	2
MPO	0.12	0.15	-9999	-10000	0	0
positive regulation of humoral immune response	0.13	0.16	-9999	-10000	0	0
IL23/IL23R/JAK2/TYK2	0.13	0.16	-9999	-10000	0	0
IL6	0.12	0.15	-9999	-10000	0	0
STAT5A	0	0	-9999	-10000	0	0
IL2	0	0.003	-9999	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	-0.005	0.004	-9999	-10000	0	0
CD3E	0.12	0.15	-9999	-10000	0	0
keratinocyte proliferation	0.13	0.16	-9999	-10000	0	0
NOS2	0.12	0.15	-9999	-10000	0	0

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.024	0.15	-9999	-0.9	1	1
TC10/GTP	-0.024	0.14	-9999	-0.87	1	1
Insulin Receptor/Insulin/IRS1/Shp2	0.002	0.01	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
APS homodimer	-0.005	0.032	-9999	-10000	0	0
GRB14	-0.11	0.36	-9999	-1.3	3	3
FOXO3	-0.008	0.027	-9999	-10000	0	0
AKT1	-0.06	0.2	-9999	-0.72	3	3
INSR	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0.002	0.011	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0	0	-9999	-10000	0	0
SORBS1	-0.036	0.22	-9999	-1.3	1	1
CRK	0	0	-9999	-10000	0	0
PTPN1	0.035	0.011	-9999	-10000	0	0
CAV1	-0.001	0.007	-9999	-10000	0	0
CBL/APS/CAP/Crk-II/C3G	-0.026	0.16	-9999	-0.95	1	1
Insulin Receptor/Insulin/IRS1/NCK2	0.002	0.01	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.001	0.007	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0	0.003	-9999	-10000	0	0
RPS6KB1	0.001	0.19	-9999	-10000	0	0
PARD6A	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.003	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.05	0.17	-9999	-10000	0	0
HRAS/GTP	0	0.005	-9999	-10000	0	0
Insulin Receptor	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.002	0.01	-9999	-10000	0	0
PRKCI	-0.012	0.042	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.065	0.22	-9999	-0.79	3	3
SHC1	0	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PI3K	0.001	0.009	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
mol:H2O2	0	0.001	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
AKT2	-0.06	0.2	-9999	-0.72	3	3
PRKCZ	-0.012	0.042	-9999	-10000	0	0
SH2B2	-0.005	0.032	-9999	-10000	0	0
SHC/SHIP	-0.002	0.01	-9999	-10000	0	0
F2RL2	-0.036	0.22	-9999	-1.3	1	1
TRIP10	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.002	0.01	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.002	0.01	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.028	0.16	-9999	-1	1	1
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.002	0.01	-9999	-10000	0	0
INPP5D	-0.003	0.013	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.004	0.012	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
IRS1	0	0	-9999	-10000	0	0
p62DOK/RasGAP	0	0	-9999	-10000	0	0
INS	-0.002	0.031	-9999	-10000	0	0
mol:PI-3-4-P2	-0.003	0.013	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
EIF4EBP1	0.001	0.19	-9999	-10000	0	0
PTPRA	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0	0.003	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.002	0.01	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS3	-0.003	0.017	-9999	-10000	0	0
Par3/Par6	-0.024	0.14	-9999	-0.88	1	1

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0	0	-9999	-10000	0	0
mol:DAG	0.04	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0	0	-9999	-10000	0	0
CaM/Ca2+	0	0	-9999	-10000	0	0
HIF1A	0	0	-9999	-10000	0	0
GAB1	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
PLCG1	0.04	0	-9999	-10000	0	0
NOS3	0.065	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
mol:NO	0.064	0	-9999	-10000	0	0
FLT1	0.029	0	-9999	-10000	0	0
PGF	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP2/VEGFR121	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
eNOS/Hsp90	0	0	-9999	-10000	0	0
endothelial cell proliferation	0.04	0.09	-9999	-10000	0	0
mol:Ca2+	0.04	0	-9999	-10000	0	0
MAPK3	0.054	0	-9999	-10000	0	0
MAPK1	0.054	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
PLGF homodimer	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	0	0	-9999	-10000	0	0
VEGFA homodimer	0	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.061	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
PRKCA	0.048	0	-9999	-10000	0	0
PRKCB	0.019	0.15	-9999	-0.87	1	1
VEGFR1 homodimer/PLGF homodimer	0	0	-9999	-10000	0	0
VEGFA	0	0	-9999	-10000	0	0
VEGFB	0	0	-9999	-10000	0	0
mol:IP3	0.04	0	-9999	-10000	0	0
RASA1	0.04	0	-9999	-10000	0	0
NRP2	0	0	-9999	-10000	0	0
VEGFR1 homodimer	0.029	0	-9999	-10000	0	0
VEGFB homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
mol:L-citrulline	0.064	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0	0	-9999	-10000	0	0
CD2AP	0	0	-9999	-10000	0	0
PI3K/GAB1	0	0	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0	0	-9999	-10000	0	0
mol:NADP	0.064	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	0	0	-9999	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HIF3A	0	0	-9999	-9999
oxygen homeostasis	0	0	-9999	-9999
TCEB2	0	0	-9999	-9999
TCEB1	0	0	-9999	-9999
HIF1A/p53	0	0	-9999	-9999
HIF1A	-0.001	0.002	-9999	-9999
COPS5	0	0	-9999	-9999
VHL/Elongin B/Elongin C/RBX1/CUL2	0	0	-9999	-9999
FIH (dimer)	0	0	-9999	-9999
CDKN2A	-0.037	0.076	-9999	-9999
ARNT/IPAS	0	0	-9999	-9999
HIF1AN	0	0	-9999	-9999
GNB2L1	0	0	-9999	-9999
HIF1A/ARNT	0	0	-9999	-9999
CUL2	0	0	-9999	-9999
OS9	0	0	-9999	-9999
RACK1/Elongin B/Elongin C	0	0	-9999	-9999
response to hypoxia	0	0	-9999	-9999
HIF1A/Hsp90	0	0	-9999	-9999
PHD1-3/OS9	-0.014	0.026	-9999	-9999
HIF1A/RACK1/Elongin B/Elongin C	0	0	-9999	-9999
VHL	0	0	-9999	-9999
HSP90AA1	0	0	-9999	-9999
HIF1A/JAB1	0	0	-9999	-9999
EGLN3	-0.043	0.08	-9999	-9999
EGLN2	0	0	-9999	-9999
EGLN1	0	0	-9999	-9999
TP53	0	0	-9999	-9999
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0	0	-9999	-9999
ARNT	0	0	-9999	-9999
ARD1A	0	0	-9999	-9999
RBX1	0	0	-9999	-9999
HIF1A/p19ARF	0.003	0.027	-9999	-9999

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.002	0.011	-9999	-10000	0	0
MAPK9	0	0	-9999	-10000	0	0
adrenocorticotropin secretion	0	0	-9999	-10000	0	0
GNB1/GNG2	0	0	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
MAPK14	0	0	-9999	-10000	0	0
Gs family/GTP	-0.003	0.015	-9999	-10000	0	0
EntrezGene:2778	0	0	-9999	-10000	0	0
vasopressin secretion	0	0	-9999	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
glutamate secretion	0.001	0.005	-9999	-10000	0	0
GNAL	-0.005	0.032	-9999	-10000	0	0
GNG2	0	0	-9999	-10000	0	0
CRH	0	0	-9999	-10000	0	0
mol:cortisol	0	0	-9999	-10000	0	0
MAPK8	-0.017	0.1	-9999	-0.61	1	1
MAPK11	0	0	-9999	-10000	0	0

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.011	0.025	-9999	-10000	0	0
PDGFB-D/PDGFRB/SLAP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/APS/CBL	-0.002	0.013	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.011	0.025	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
FGR	0.003	0.007	-9999	-10000	0	0
mol:Ca2+	0.038	0.007	-9999	-10000	0	0
MYC	0.062	0.009	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	0	0	-9999	-10000	0	0
GRB10	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0.038	0.007	-9999	-10000	0	0
PTEN	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
GRB7	-0.036	0.22	-9999	-1.3	1	1
PDGFB-D/PDGFRB/SHP2	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0	0	-9999	-10000	0	0
cell cycle arrest	0	0	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
HIF1A	0.069	0.001	-9999	-10000	0	0
GAB1	0.043	0.011	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.046	0.013	-9999	-10000	0	0
PDGFB-D/PDGFRB	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0	0	-9999	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.012	0.025	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	0.038	0.007	-9999	-10000	0	0
E5	0	0	-9999	-10000	0	0
CSK	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.03	0.18	-9999	-1.1	1	1
SHB	0	0	-9999	-10000	0	0
BLK	0.003	0.007	-9999	-10000	0	0
PTPN2	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
VAV2	0.049	0.01	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0	0	-9999	-10000	0	0
LCK	0.003	0.007	-9999	-10000	0	0
PDGFRB	0	0	-9999	-10000	0	0
ACP1	0	0	-9999	-10000	0	0
HCK	0.003	0.007	-9999	-10000	0	0
ABL1	0.04	0.008	-9999	-10000	0	0
PDGFB-D/PDGFRB/CBL	0.042	0.009	-9999	-10000	0	0
PTPN1	0	0	-9999	-10000	0	0
SNX15	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
STAT1	0	0	-9999	-10000	0	0
cell proliferation	0.06	0.009	-9999	-10000	0	0
SLA	0	0	-9999	-10000	0	0
actin cytoskeleton reorganization	0	0	-9999	-10000	0	0
SRC	0.003	0.007	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.027	0.16	-9999	-0.98	1	1
SH2B2	-0.005	0.032	-9999	-10000	0	0
PLCgamma1/SPHK1	0.012	0.026	-9999	-10000	0	0
LYN	0.003	0.007	-9999	-10000	0	0
LRP1	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
STAT5B	0	0	-9999	-10000	0	0
STAT5A	0	0	-9999	-10000	0	0
NCK1-2/p130 Cas	0	0	-9999	-10000	0	0
SPHK1	-0.032	0.071	-9999	-10000	0	0
EDG1	0.001	0	-9999	-10000	0	0
mol:DAG	0.038	0.007	-9999	-10000	0	0
PLCG1	0.038	0.007	-9999	-10000	0	0
NHERF/PDGFRB	0	0	-9999	-10000	0	0
YES1	0.003	0.007	-9999	-10000	0	0
cell migration	0	0	-9999	-10000	0	0
SHC/Grb2/SOS1	0	0	-9999	-10000	0	0
SLC9A3R2	0	0	-9999	-10000	0	0
SLC9A3R1	0	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0	0	-9999	-10000	0	0
FYN	0.003	0.007	-9999	-10000	0	0
DOK1	0	0	-9999	-10000	0	0
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0	0	-9999	-10000	0	0
RAC1	0.06	0.01	-9999	-10000	0	0
PRKCD	0.001	0.006	-9999	-10000	0	0
FER	0.001	0.006	-9999	-10000	0	0
MAPKKK cascade	0	0	-9999	-10000	0	0
RASA1	0.001	0.006	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
p62DOK/Csk	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	0	0	-9999	-10000	0	0
chemotaxis	0.039	0.008	-9999	-10000	0	0
STAT1-3-5/STAT1-3-5	0	0	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0	0	-9999	-10000	0	0
PTPRJ	0	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0	0	-9999	-10000	0	0
adherens junction organization	0.041	0.012	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	-0.039	0.16	-9999	-0.71	2	2
FMN1	-0.007	0.016	-9999	-10000	0	0
mol:IP3	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.001	0.004	-9999	-10000	0	0
CTNND1	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.044	0	-9999	-10000	0	0
VASP	0	0	-9999	-10000	0	0
ZYX	0	0	-9999	-10000	0	0
JUB	0	0	-9999	-10000	0	0
EGFR(dimer)	-0.046	0.19	-9999	-0.83	2	2
E-cadherin/beta catenin-gamma catenin	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
FYN	-0.004	0.18	-9999	-0.58	3	3
mol:Ca2+	0	0	-9999	-10000	0	0
JUP	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
CDH1	0	0	-9999	-10000	0	0
RhoA/GDP	-0.039	0.16	-9999	-0.71	2	2
establishment of polarity of embryonic epithelium	0.044	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
EGFR	-0.073	0.3	-9999	-1.3	2	2
CASR	-0.069	0.22	-9999	-0.8	3	3
RhoA/GTP	0	0	-9999	-10000	0	0
AKT2	0	0	-9999	-10000	0	0
actin cable formation	0.037	0.031	-9999	-10000	0	0
apoptosis	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
mol:GDP	-0.044	0.18	-9999	-0.78	2	2
PIP5K1A	0	0	-9999	-10000	0	0
PLCG1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.041	0.17	-9999	-0.74	2	2
homophilic cell adhesion	0.001	0	-9999	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
E-cadherin/beta catenin-gamma catenin	-9999	-9999
E-cadherin/beta catenin	-9999	-9999
CTNNB1	-9999	-9999
JUP	-9999	-9999
CDH1	-9999	-9999

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	0.026	0.038	-9999	-10000	0	0
CRKL	0.021	0.039	-9999	-10000	0	0
HRAS	-0.002	0.01	-9999	-10000	0	0
mol:PIP3	0.005	0.036	-9999	-10000	0	0
SPRED1	0	0	-9999	-10000	0	0
SPRED2	0	0	-9999	-10000	0	0
GAB1	-0.015	0.02	-9999	-10000	0	0
FOXO3	0.025	0.036	-9999	-10000	0	0
AKT1	0.018	0.037	-9999	-10000	0	0
BAD	0.025	0.036	-9999	-10000	0	0
megakaryocyte differentiation	0.013	0.04	-9999	-10000	0	0
GSK3B	0.025	0.036	-9999	-10000	0	0
RAF1	0.044	0.037	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
STAT3	-0.012	0.024	-9999	-10000	0	0
STAT1	-0.01	0.11	-9999	-10000	0	0
HRAS/SPRED1	-0.001	0.007	-9999	-10000	0	0
cell proliferation	-0.011	0.14	-9999	-0.81	1	1
PIK3CA	0	0	-9999	-10000	0	0
TEC	0	0	-9999	-10000	0	0
RPS6KB1	0.014	0.038	-9999	-10000	0	0
HRAS/SPRED2	-0.001	0.007	-9999	-10000	0	0
LYN/TEC/p62DOK	-0.008	0.012	-9999	-10000	0	0
MAPK3	0.049	0.029	-9999	-10000	0	0
STAP1	-0.015	0.025	-9999	-10000	0	0
GRAP2	-0.005	0.032	-9999	-10000	0	0
JAK2	-0.052	0.073	-9999	-10000	0	0
STAT1 (dimer)	-0.009	0.11	-9999	-10000	0	0
mol:Gleevec	-0.001	0.003	-9999	-10000	0	0
GRB2/SOCS1/VAV1	-0.011	0.02	-9999	-10000	0	0
actin filament polymerization	0.011	0.041	-9999	-10000	0	0
LYN	0	0	-9999	-10000	0	0
STAP1/STAT5A (dimer)	-0.021	0.037	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
CBL/CRKL/GRB2	-0.005	0.007	-9999	-10000	0	0
PI3K	-0.008	0.01	-9999	-10000	0	0
PTEN	0	0	-9999	-10000	0	0
SCF/KIT/EPO/EPOR	-0.28	0.39	-9999	-0.84	12	12
MAPK8	-0.036	0.14	-9999	-0.84	1	1
STAT3 (dimer)	0.013	0.04	-9999	-10000	0	0
positive regulation of transcription	0.045	0.027	-9999	-10000	0	0
mol:GDP	-0.004	0.018	-9999	-10000	0	0
PIK3C2B	-0.012	0.024	-9999	-10000	0	0
CBL/CRKL	-0.008	0.011	-9999	-10000	0	0
FER	-0.012	0.024	-9999	-10000	0	0
SH2B3	-0.012	0.024	-9999	-10000	0	0
PDPK1	0.012	0.035	-9999	-10000	0	0
SNAI2	-0.012	0.024	-9999	-10000	0	0
positive regulation of cell proliferation	0.005	0.079	-9999	-10000	0	0
KITLG	0.01	0.008	-9999	-10000	0	0
cell motility	0.005	0.079	-9999	-10000	0	0
PTPN6	0.005	0.007	-9999	-10000	0	0
EPOR	0.027	0.04	-9999	-10000	0	0
STAT5A (dimer)	0.007	0.07	-9999	-10000	0	0
SOCS1	-0.005	0.032	-9999	-10000	0	0
cell migration	-0.013	0.04	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
EPO	-0.43	0.62	-9999	-1.3	12	12
VAV1	-0.005	0.032	-9999	-10000	0	0
GRB10	-0.015	0.02	-9999	-10000	0	0
PTPN11	0.005	0.006	-9999	-10000	0	0
SCF/KIT	-0.019	0.025	-9999	-10000	0	0
GO:0007205	-0.001	0.004	-9999	-10000	0	0
MAP2K1	0.048	0.031	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
KIT	0.025	0.041	-9999	-10000	0	0
MAP2K2	0.048	0.031	-9999	-10000	0	0
SHC/Grb2/SOS1	-0.008	0.012	-9999	-10000	0	0
STAT5A	0.006	0.071	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
response to radiation	0.013	0.04	-9999	-10000	0	0
SHC/GRAP2	-0.003	0.019	-9999	-10000	0	0
PTPRO	-0.012	0.024	-9999	-10000	0	0
SH2B2	-0.014	0.024	-9999	-10000	0	0
DOK1	0	0	-9999	-10000	0	0
MATK	-0.012	0.024	-9999	-10000	0	0
CREBBP	0.03	0.009	-9999	-10000	0	0
BCL2	0.03	0.036	-9999	-10000	0	0

×

Arf1 pathway

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
coatomer protein complex	0	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.02	0	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0	-9999	-10000	0	0
CD4	-0.036	0.22	-9999	-1.3	1	1
CLTA	0	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0	0	-9999	-10000	0	0
AP2M1	0	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0	-9999	-10000	0	0
ARFIP2	0	0	-9999	-10000	0	0
COPA	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.025	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	-0.01	0.06	-9999	-0.37	1	1
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.011	0	-9999	-10000	0	0
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.011	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.027	0.16	-9999	-0.98	1	1

×

Alternative NF-kappaB pathway

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.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	-9999	-9999
FBXW11	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	-9999	-9999
CHUK	-9999	-9999
NF kappa B2 p100/RelB	-9999	-9999
NFKB1	-9999	-9999
MAP3K14	-9999	-9999
NF kappa B1 p50/RelB	-9999	-9999
RELB	-9999	-9999
NFKB2	-9999	-9999
NF kappa B2 p52/RelB	-9999	-9999
regulation of B cell activation	-9999	-9999

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.022	0	-9999	-10000	0	0
SMARCC1	0.01	0.012	-9999	-10000	0	0
REL	-0.036	0.22	-9999	-1.3	1	1
HDAC7	-0.026	0.17	-9999	-0.91	1	1
JUN	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
KAT5	0	0	-9999	-10000	0	0
MAPK14	0.024	0.007	-9999	-10000	0	0
FOXO1	0	0	-9999	-10000	0	0
T-DHT/AR	-0.036	0.18	-9999	-0.99	1	1
MAP2K6	0	0	-9999	-10000	0	0
BRM/BAF57	-0.03	0.18	-9999	-1.1	1	1
MAP2K4	0	0	-9999	-10000	0	0
SMARCA2	-0.036	0.22	-9999	-1.3	1	1
PDE9A	0.002	0.032	-9999	-10000	0	0
NCOA2	-0.073	0.3	-9999	-1.3	2	2
CEBPA	-0.22	0.49	-9999	-1.3	6	6
EHMT2	0	0	-9999	-10000	0	0
cell proliferation	0.004	0.15	-9999	-0.7	1	1
NR0B1	-0.005	0.032	-9999	-10000	0	0
EGR1	-0.036	0.22	-9999	-1.3	1	1
RXRs/9cRA	0	0	-9999	-10000	0	0
AR/RACK1/Src	-0.073	0.16	-9999	-0.97	1	1
AR/GR	-0.2	0.24	-9999	-1.1	1	1
GNB2L1	0	0	-9999	-10000	0	0
PKN1	0	0	-9999	-10000	0	0
RCHY1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
MAPK8	-0.006	0.18	-9999	-1.1	1	1
T-DHT/AR/TIF2/CARM1	-0.12	0.3	-9999	-1.3	2	2
SRC	0.021	0.15	-9999	-0.86	1	1
NR3C1	0	0	-9999	-10000	0	0
KLK3	0.011	0.051	-9999	-10000	0	0
APPBP2	0	0	-9999	-10000	0	0
TRIM24	0	0	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.082	0.17	-9999	-1	1	1
TMPRSS2	-0.036	0.25	-9999	-1.5	1	1
RXRG	0	0	-9999	-10000	0	0
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0	0	-9999	-10000	0	0
RXRB	0	0	-9999	-10000	0	0
CARM1	0	0	-9999	-10000	0	0
NR2C2	0	0	-9999	-10000	0	0
KLK2	-0.038	0.17	-9999	-0.81	1	1
AR	-0.2	0.28	-9999	-0.46	17	17
SENP1	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
MDM2	0	0	-9999	-10000	0	0
SRY	0	0	-9999	-10000	0	0
GATA2	-0.005	0.032	-9999	-10000	0	0
MYST2	0	0	-9999	-10000	0	0
HOXB13	0	0	-9999	-10000	0	0
T-DHT/AR/RACK1/Src	-0.075	0.16	-9999	-1	1	1
positive regulation of transcription	-0.005	0.032	-9999	-10000	0	0
DNAJA1	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
NCOA1	0.009	0.009	-9999	-10000	0	0
SPDEF	-0.059	0.089	-9999	-10000	0	0
T-DHT/AR/TIF2	-0.044	0.21	-9999	-0.81	2	2
T-DHT/AR/Hsp90	-0.082	0.17	-9999	-1	1	1
GSK3B	0.007	0.008	-9999	-10000	0	0
NR2C1	0	0	-9999	-10000	0	0
mol:T-DHT	0.014	0.16	-9999	-0.92	1	1
SIRT1	0	0	-9999	-10000	0	0
ZMIZ2	0	0	-9999	-10000	0	0
POU2F1	0.025	0.004	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.087	0.18	-9999	-1	1	1
CREBBP	0	0	-9999	-10000	0	0
SMARCE1	0	0	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.042	0.12	-9999	-10000	0	0
MAP3K8	0	0	-9999	-10000	0	0
FOS	0.019	0.092	-9999	-10000	0	0
PRKCA	0	0	-9999	-10000	0	0
PTPN7	0.006	0.033	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
PRKCB	-0.042	0.22	-9999	-1.3	1	1
NRAS	0	0	-9999	-10000	0	0
RAS family/GTP	0	0	-9999	-10000	0	0
MAPK3	0.02	0.053	-9999	-10000	0	0
MAP2K1	0.014	0.13	-9999	-0.71	1	1
ELK1	-0.001	0.004	-9999	-10000	0	0
BRAF	-0.023	0.12	-9999	-0.73	1	1
mol:GTP	0	0.002	-9999	-0.007	3	3
MAPK1	0.02	0.053	-9999	-10000	0	0
RAF1	-0.023	0.12	-9999	-0.73	1	1
KRAS	0	0	-9999	-10000	0	0

×

Aurora B 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.023	0.032	-9999	-10000	0	0
STMN1	-0.015	0.06	-9999	-10000	0	0
Aurora B/RasGAP/Survivin	-0.069	0.078	-9999	-10000	0	0
Chromosomal passenger complex/Cul3 protein complex	-0.012	0.024	-9999	-10000	0	0
BIRC5	-0.1	0.097	-9999	-10000	0	0
DES	-0.01	0.11	-9999	-0.66	1	1
Aurora C/Aurora B/INCENP	-0.045	0.15	-9999	-0.94	1	1
Aurora B/TACC1	-0.024	0.041	-9999	-10000	0	0
Aurora B/PP2A	-0.03	0.05	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.001	0.009	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0	0.002	-9999	-10000	0	0
NDC80	-0.074	0.11	-9999	-10000	0	0
Cul3 protein complex	0	0	-9999	-10000	0	0
KIF2C	-0.016	0.021	-9999	-10000	0	0
PEBP1	0	0	-9999	-10000	0	0
KIF20A	-0.077	0.099	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.03	0.05	-9999	-10000	0	0
SEPT1	-0.005	0.032	-9999	-10000	0	0
SMC2	0	0	-9999	-10000	0	0
SMC4	0	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	0.02	0.015	-9999	-10000	0	0
PSMA3	0	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.001	-9999	-10000	0	0
H3F3B	-0.006	0.025	-9999	-10000	0	0
AURKB	-0.05	0.091	-9999	-10000	0	0
AURKC	-0.036	0.22	-9999	-1.3	1	1
CDCA8	-0.044	0.082	-9999	-10000	0	0
cytokinesis	-0.035	0.046	-9999	-10000	0	0
Aurora B/Septin1	-0.03	0.049	-9999	-10000	0	0
AURKA	0	0	-9999	-10000	0	0
INCENP	0	0.002	-9999	-10000	0	0
KLHL13	0	0	-9999	-10000	0	0
BUB1	-0.16	0.072	-9999	-10000	0	0
hSgo1/Aurora B/Survivin	-0.067	0.078	-9999	-10000	0	0
EVI5	0	0	-9999	-10000	0	0
RhoA/GTP	-0.043	0.059	-9999	-10000	0	0
SGOL1	-0.011	0.044	-9999	-10000	0	0
CENPA	-0.011	0.034	-9999	-10000	0	0
NCAPG	-0.11	0.095	-9999	-10000	0	0
Aurora B/HC8 Proteasome	-0.03	0.05	-9999	-10000	0	0
NCAPD2	0	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.03	0.05	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
NCAPH	-0.091	0.096	-9999	-10000	0	0
NPM1	-0.001	0.014	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
KLHL9	0	0	-9999	-10000	0	0
mitotic prometaphase	-0.003	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.03	0.05	-9999	-10000	0	0
PPP1CC	0	0	-9999	-10000	0	0
Centraspindlin	-0.051	0.067	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.001	0.014	-9999	-10000	0	0
MYLK	-0.006	0.025	-9999	-10000	0	0
KIF23	-0.065	0.092	-9999	-10000	0	0
VIM	-0.018	0.069	-9999	-10000	0	0
RACGAP1	-0.005	0.032	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	-0.001	0.014	-9999	-10000	0	0
Chromosomal passenger complex	-0.028	0.043	-9999	-10000	0	0
Chromosomal passenger complex/EVI5	-0.057	0.098	-9999	-10000	0	0
TACC1	0	0	-9999	-10000	0	0
PPP2R5D	0	0	-9999	-10000	0	0
CUL3	0	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

pid_entity	TCGA.ZU.A8S4	TCGA.ZH.A8Y8	TCGA.ZH.A8Y6	TCGA.ZH.A8Y5
109_MAP3K5	0.054	0.054	0.054	0.054
47_PPARGC1A	0	0	0	0
105_BMP4	0	0	0	0
105_BMP6	0	0	0	0
105_BMP7	0	0	0	-0.19
105_BMP2	0	0	0	0
131_RELN/VLDLR	-0.062	-0.062	-0.92	-0.92
30_TGFB1/TGF beta receptor Type II	0	0	0	0
84_STAT5B	0.027	0.041	0.043	0.041
84_STAT5A	0.027	0.041	0.043	0.041