Lung Adenocarcinoma: PARADIGM pathway analysis of mRNASeq expression data<BR>(primary solid tumor cohort)

Pathway.Name	Avg.Num.Perturbations
Glypican 2 network	130
FOXM1 transcription factor network	100
Aurora B signaling	93
Angiopoietin receptor Tie2-mediated signaling	91
Signaling events mediated by the Hedgehog family	71
Aurora C signaling	55
PLK1 signaling events	53
Osteopontin-mediated events	51
HIF-1-alpha transcription factor network	50
Endothelins	48

Pathway.Name	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
Glypican 2 network	130	522	4	-0.2	-0.11	1000	-1000	-0.031	-1000
FOXM1 transcription factor network	100	5142	51	-0.63	0.01	1000	-1000	-0.19	-1000
Aurora B signaling	93	6250	67	-0.44	0.01	1000	-1000	-0.055	-1000
Angiopoietin receptor Tie2-mediated signaling	91	8037	88	-0.53	0.05	1000	-1000	-0.11	-1000
Signaling events mediated by the Hedgehog family	71	3727	52	-0.38	0.18	1000	-1000	-0.074	-1000
Aurora C signaling	55	385	7	-0.28	0.005	1000	-1000	-0.032	-1000
PLK1 signaling events	53	4511	85	-0.31	0.066	1000	-1000	-0.041	-1000
Osteopontin-mediated events	51	1975	38	-0.39	0.011	1000	-1000	-0.084	-1000
HIF-1-alpha transcription factor network	50	3855	76	-0.5	0.016	1000	-1000	-0.16	-1000
Endothelins	48	4616	96	-0.29	0.035	1000	-1000	-0.077	-1000
Signaling events regulated by Ret tyrosine kinase	44	3670	82	-0.17	0.01	1000	-1000	-0.072	-1000
Visual signal transduction: Cones	41	1564	38	-0.16	0.01	1000	-1000	-0.052	-1000
IL4-mediated signaling events	40	3704	91	-0.8	0.52	1000	-1000	-0.18	-1000
amb2 Integrin signaling	36	3016	82	-0.48	0.01	1000	-1000	-0.066	-1000
Signaling mediated by p38-alpha and p38-beta	36	1614	44	-0.11	0.01	1000	-1000	-0.046	-1000
BMP receptor signaling	35	2863	81	-0.38	0.027	1000	-1000	-0.085	-1000
FOXA2 and FOXA3 transcription factor networks	33	1522	46	-0.51	0.016	1000	-1000	-0.1	-1000
Fc-epsilon receptor I signaling in mast cells	33	3241	97	-0.15	0.028	1000	-1000	-0.075	-1000
TCGA08_retinoblastoma	32	262	8	-0.15	0.049	1000	-1000	-0.025	-1000
Visual signal transduction: Rods	31	1641	52	-0.15	0.01	1000	-1000	-0.064	-1000
TCGA08_p53	30	212	7	-0.11	0.053	1000	-1000	-0.018	-1000
Glucocorticoid receptor regulatory network	29	3324	114	-0.39	0.25	1000	-1000	-0.065	-1000
p75(NTR)-mediated signaling	27	3380	125	-0.3	0.016	1000	-1000	-0.086	-1000
LPA4-mediated signaling events	26	317	12	-0.12	0.013	1000	-1000	-0.023	-1000
Canonical Wnt signaling pathway	25	1275	51	-0.34	0.15	1000	-1000	-0.052	-1000
Arf6 signaling events	24	1491	62	-0.19	0.011	1000	-1000	-0.057	-1000
Integrins in angiogenesis	23	1977	84	-0.39	0.025	1000	-1000	-0.076	-1000
Syndecan-1-mediated signaling events	22	754	34	-0.36	0.01	1000	-1000	-0.057	-1000
Presenilin action in Notch and Wnt signaling	22	1366	61	-0.34	0.021	1000	-1000	-0.065	-1000
Aurora A signaling	22	1360	60	-0.31	0.016	1000	-1000	-0.053	-1000
Glypican 1 network	22	1076	48	-0.1	0.019	1000	-1000	-0.042	-1000
RXR and RAR heterodimerization with other nuclear receptor	22	1149	52	-0.25	0.042	1000	-1000	-0.054	-1000
Ephrin B reverse signaling	22	1078	48	-0.096	0.062	1000	-1000	-0.06	-1000
Effects of Botulinum toxin	22	584	26	-0.077	0.01	1000	-1000	-0.051	-1000
Neurotrophic factor-mediated Trk receptor signaling	21	2533	120	-0.24	0.2	1000	-1000	-0.063	-1000
Thromboxane A2 receptor signaling	20	2132	105	-0.091	0.023	1000	-1000	-0.06	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	19	1351	68	-0.14	0.035	1000	-1000	-0.12	-1000
EGFR-dependent Endothelin signaling events	19	405	21	-0.091	0.01	1000	-1000	-0.051	-1000
IL23-mediated signaling events	19	1162	60	-0.27	0.017	1000	-1000	-0.17	-1000
PLK2 and PLK4 events	16	48	3	-0.025	-0.008	1000	-1000	-0.015	-1000
PDGFR-alpha signaling pathway	16	718	44	-0.3	0.018	1000	-1000	-0.055	-1000
Wnt signaling	16	116	7	-0.066	0.008	1000	-1000	-0.024	-1000
IL6-mediated signaling events	16	1254	75	-0.33	0.042	1000	-1000	-0.094	-1000
ErbB4 signaling events	15	1057	69	-0.19	0.2	1000	-1000	-0.082	-1000
Class IB PI3K non-lipid kinase events	15	45	3	-0.012	-1000	1000	-1000	-0.011	-1000
HIF-2-alpha transcription factor network	14	634	43	-0.14	0.073	1000	-1000	-0.093	-1000
Nongenotropic Androgen signaling	14	756	52	-0.049	0.01	1000	-1000	-0.055	-1000
Regulation of Androgen receptor activity	14	984	70	-0.25	0.029	1000	-1000	-0.061	-1000
Syndecan-2-mediated signaling events	13	915	69	-0.092	0.03	1000	-1000	-0.046	-1000
Reelin signaling pathway	13	774	56	-0.099	0.01	1000	-1000	-0.066	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	13	448	33	-0.15	0.021	1000	-1000	-0.055	-1000
Noncanonical Wnt signaling pathway	12	320	26	-0.066	0.01	1000	-1000	-0.068	-1000
Syndecan-4-mediated signaling events	12	840	67	-0.19	0.014	1000	-1000	-0.079	-1000
Coregulation of Androgen receptor activity	11	874	76	-0.15	0.018	1000	-1000	-0.047	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	11	883	78	-0.044	0.037	1000	-1000	-0.067	-1000
IL12-mediated signaling events	10	939	87	-0.096	0.04	1000	-1000	-0.12	-1000
Nectin adhesion pathway	10	639	63	-0.033	0.02	1000	-1000	-0.057	-1000
Calcium signaling in the CD4+ TCR pathway	10	330	31	-0.11	0.011	1000	-1000	-0.076	-1000
Ephrin A reverse signaling	9	66	7	-0.012	0.006	1000	-1000	-0.029	-1000
Signaling events mediated by PTP1B	9	712	76	-0.09	0.016	1000	-1000	-0.072	-1000
Signaling events mediated by HDAC Class III	9	393	40	-0.11	0.018	1000	-1000	-0.034	-1000
FAS signaling pathway (CD95)	9	441	47	-0.23	0.014	1000	-1000	-0.039	-1000
Syndecan-3-mediated signaling events	9	334	35	-0.2	0.01	1000	-1000	-0.059	-1000
EPHB forward signaling	9	800	85	-0.069	0.051	1000	-1000	-0.075	-1000
BCR signaling pathway	9	913	99	-0.13	0.027	1000	-1000	-0.074	-1000
Caspase cascade in apoptosis	8	598	74	-0.046	0.03	1000	-1000	-0.045	-1000
Nephrin/Neph1 signaling in the kidney podocyte	8	284	34	-0.031	0.013	1000	-1000	-0.056	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	8	479	54	-0.14	0.021	1000	-1000	-0.086	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	8	745	85	-0.046	0.032	1000	-1000	-0.068	-1000
S1P1 pathway	8	307	36	-0.054	0.014	1000	-1000	-0.048	-1000
LPA receptor mediated events	8	866	102	-0.1	0.031	1000	-1000	-0.077	-1000
Signaling events mediated by PRL	8	298	34	-0.18	0.02	1000	-1000	-0.049	-1000
BARD1 signaling events	7	406	57	-0.18	0.03	1000	-1000	-0.06	-1000
IL1-mediated signaling events	7	494	62	-0.14	0.049	1000	-1000	-0.078	-1000
TCR signaling in naïve CD8+ T cells	7	671	93	-0.073	0.043	1000	-1000	-0.074	-1000
Signaling events mediated by VEGFR1 and VEGFR2	7	973	125	-0.3	0.041	1000	-1000	-0.096	-1000
IL2 signaling events mediated by STAT5	7	167	22	-0.14	0.053	1000	-1000	-0.054	-1000
S1P4 pathway	7	176	25	-0.031	0.01	1000	-1000	-0.051	-1000
ErbB2/ErbB3 signaling events	6	429	65	-0.085	0.021	1000	-1000	-0.063	-1000
Regulation of p38-alpha and p38-beta	6	345	54	-0.066	0.021	1000	-1000	-0.055	-1000
Arf6 trafficking events	6	458	71	-0.086	0.034	1000	-1000	-0.062	-1000
Plasma membrane estrogen receptor signaling	6	568	86	-0.031	0.029	1000	-1000	-0.078	-1000
Regulation of nuclear SMAD2/3 signaling	5	807	136	-0.1	0.05	1000	-1000	-0.065	-1000
Sphingosine 1-phosphate (S1P) pathway	5	146	28	-0.031	0.019	1000	-1000	-0.046	-1000
S1P5 pathway	5	101	17	-0.031	0.029	1000	-1000	-0.052	-1000
IL27-mediated signaling events	5	267	51	-0.1	0.011	1000	-1000	-0.071	-1000
Regulation of Telomerase	5	522	102	-0.093	0.032	1000	-1000	-0.097	-1000
Cellular roles of Anthrax toxin	4	162	39	-0.04	0.016	1000	-1000	-0.025	-1000
Hedgehog signaling events mediated by Gli proteins	4	294	65	-0.18	0.055	1000	-1000	-0.06	-1000
FoxO family signaling	4	269	64	-0.14	0.054	1000	-1000	-0.084	-1000
Signaling mediated by p38-gamma and p38-delta	4	64	15	0	0.02	1000	-1000	-0.032	-1000
Retinoic acid receptors-mediated signaling	4	252	58	-0.16	0.033	1000	-1000	-0.061	-1000
Insulin Pathway	4	321	74	-0.15	0.03	1000	-1000	-0.077	-1000
VEGFR1 specific signals	4	267	56	-0.3	0.041	1000	-1000	-0.069	-1000
p38 MAPK signaling pathway	4	202	44	-0.077	0.027	1000	-1000	-0.058	-1000
Ras signaling in the CD4+ TCR pathway	4	68	17	-0.011	0.021	1000	-1000	-0.04	-1000
Signaling events mediated by HDAC Class II	3	289	75	-0.044	0.027	1000	-1000	-0.055	-1000
Circadian rhythm pathway	3	81	22	-0.037	0.033	1000	-1000	-0.056	-1000
JNK signaling in the CD4+ TCR pathway	3	57	17	-0.013	0.031	1000	-1000	-0.054	-1000
Arf6 downstream pathway	3	146	43	-0.054	0.027	1000	-1000	-0.035	-1000
IFN-gamma pathway	3	215	68	-0.076	0.047	1000	-1000	-0.087	-1000
Ceramide signaling pathway	3	289	76	-0.091	0.034	1000	-1000	-0.055	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	3	271	83	-0.06	0.04	1000	-1000	-0.075	-1000
Signaling events mediated by HDAC Class I	3	315	104	-0.052	0.043	1000	-1000	-0.066	-1000
IL2 signaling events mediated by PI3K	3	183	58	-0.13	0.064	1000	-1000	-0.077	-1000
Stabilization and expansion of the E-cadherin adherens junction	3	278	74	-0.12	0.061	1000	-1000	-0.077	-1000
Class I PI3K signaling events	3	259	73	-0.054	0.025	1000	-1000	-0.064	-1000
TRAIL signaling pathway	2	103	48	-0.01	0.04	1000	-1000	-0.057	-1000
TCGA08_rtk_signaling	2	63	26	-0.024	0.037	1000	-1000	-0.018	-1000
E-cadherin signaling in the nascent adherens junction	2	160	76	-0.055	0.05	1000	-1000	-0.071	-1000
S1P3 pathway	2	118	42	-0.03	0.022	1000	-1000	-0.057	-1000
Canonical NF-kappaB pathway	1	42	39	-0.017	0.066	1000	-1000	-0.072	-1000
a4b1 and a4b7 Integrin signaling	1	8	5	-0.003	0.008	1000	-1000	-0.036	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	1	83	45	-0.015	0.061	1000	-1000	-0.088	-1000
IGF1 pathway	1	94	57	-0.04	0.043	1000	-1000	-0.079	-1000
Rapid glucocorticoid signaling	1	34	20	-0.005	0.01	1000	-1000	-0.029	-1000
PDGFR-beta signaling pathway	1	188	97	-0.045	0.048	1000	-1000	-0.066	-1000
E-cadherin signaling events	1	8	5	-0.003	0.01	1000	-1000	-0.038	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0	9	23	-0.003	0.036	1000	-1000	-0.063	-1000
EPO signaling pathway	0	37	55	-0.004	0.06	1000	-1000	-0.084	-1000
Insulin-mediated glucose transport	0	19	32	-0.004	0.034	1000	-1000	-0.055	-1000
mTOR signaling pathway	0	10	53	-0.001	0.026	1000	-1000	-0.054	-1000
Class I PI3K signaling events mediated by Akt	0	22	68	-0.033	0.046	1000	-1000	-0.057	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0	35	37	-0.005	0.027	1000	-1000	-0.064	-1000
ceramide signaling pathway	0	45	49	-0.015	0.037	1000	-1000	-0.041	-1000
Paxillin-dependent events mediated by a4b1	0	18	36	-0.004	0.018	1000	-1000	-0.061	-1000
Atypical NF-kappaB pathway	0	8	31	-0.002	0.038	1000	-1000	-0.061	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0	14	27	-0.002	0.023	1000	-1000	-0.044	-1000
E-cadherin signaling in keratinocytes	0	25	43	-0.007	0.038	1000	-1000	-0.057	-1000
Arf1 pathway	0	12	54	-0.005	0.025	1000	-1000	-0.039	-1000
Alternative NF-kappaB pathway	0	0	13	0	0.01	1000	-1000	-0.057	-1000
Total	2084	120820	7203	-19	-1000	131000	-131000	-8.4	-131000

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.17	0.25	-9999	-0.52	117	117
GPC2	-0.11	0.22	-9999	-0.52	81	81
GPC2/Midkine	-0.2	0.24	-9999	-0.44	162	162
neuron projection morphogenesis	-0.2	0.24	-9999	-0.44	162	162

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.49	0.55	-9999	-1.1	131	131
PLK1	-0.16	0.2	-9999	-10000	0	0
BIRC5	-0.2	0.2	-9999	-10000	0	0
HSPA1B	-0.49	0.55	-9999	-1.1	131	131
MAP2K1	-0.004	0.034	-9999	-10000	0	0
BRCA2	-0.49	0.55	-9999	-1.1	131	131
FOXM1	-0.63	0.71	-9999	-1.3	154	154
XRCC1	-0.49	0.55	-9999	-1.1	131	131
FOXM1B/p19	-0.56	0.5	-9999	-1.1	144	144
Cyclin D1/CDK4	-0.48	0.5	-9999	-0.98	137	137
CDC2	-0.52	0.58	-9999	-1.1	154	154
TGFA	-0.47	0.49	-9999	-0.95	139	139
SKP2	-0.49	0.55	-9999	-1.1	130	130
CCNE1	-0.19	0.26	-9999	-0.54	127	127
CKS1B	-0.49	0.56	-9999	-1.1	134	134
RB1	-0.24	0.18	-9999	-0.47	33	33
FOXM1C/SP1	-0.56	0.62	-9999	-1.2	140	140
AURKB	-0.18	0.2	-9999	-10000	0	0
CENPF	-0.55	0.59	-9999	-1.1	157	157
CDK4	0.001	0.051	-9999	-0.54	3	3
MYC	-0.42	0.48	-9999	-0.92	131	131
CHEK2	-0.013	0.081	-9999	-0.57	6	6
ONECUT1	-0.52	0.54	-9999	-1.1	143	143
CDKN2A	-0.15	0.24	-9999	-0.52	104	104
LAMA4	-0.5	0.55	-9999	-1.1	135	135
FOXM1B/HNF6	-0.62	0.64	-9999	-1.3	143	143
FOS	-0.51	0.58	-9999	-1.1	135	135
SP1	0.01	0.001	-9999	-10000	0	0
CDC25B	-0.49	0.55	-9999	-1.1	131	131
response to radiation	-0.015	0.031	-9999	-10000	0	0
CENPB	-0.49	0.55	-9999	-1	136	136
CENPA	-0.57	0.6	-9999	-1.1	161	161
NEK2	-0.57	0.6	-9999	-1.1	165	165
HIST1H2BA	-0.49	0.55	-9999	-1.1	132	132
CCNA2	-0.14	0.24	-9999	-0.54	98	98
EP300	0.01	0	-9999	-10000	0	0
CCNB1/CDK1	-0.58	0.64	-9999	-1.3	136	136
CCNB2	-0.56	0.6	-9999	-1.1	155	155
CCNB1	-0.54	0.6	-9999	-1.2	137	137
ETV5	-0.49	0.55	-9999	-1.1	132	132
ESR1	-0.5	0.56	-9999	-1.1	130	130
CCND1	-0.49	0.52	-9999	-1	140	140
GSK3A	0	0.027	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.19	0.27	-9999	-0.48	153	153
CDK2	0.005	0.008	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.019	0.038	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.6	0.5	-9999	-1.1	154	154
GAS1	-0.5	0.56	-9999	-1.1	136	136
MMP2	-0.49	0.55	-9999	-1.1	133	133
RB1/FOXM1C	-0.52	0.55	-9999	-1.1	140	140
CREBBP	0.01	0	-9999	-10000	0	0

×

Aurora B 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.16	0.17	-9999	-0.33	156	156
STMN1	-0.19	0.2	-9999	-0.37	190	190
Aurora B/RasGAP/Survivin	-0.33	0.27	-9999	-0.52	226	226
Chromosomal passenger complex/Cul3 protein complex	-0.14	0.15	-9999	-0.3	136	136
BIRC5	-0.32	0.26	-9999	-0.53	213	213
DES	-0.42	0.38	-9999	-0.76	191	191
Aurora C/Aurora B/INCENP	-0.15	0.15	-9999	-0.28	192	192
Aurora B/TACC1	-0.17	0.17	-9999	-0.32	193	193
Aurora B/PP2A	-0.19	0.19	-9999	-0.37	190	190
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.036	0.045	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.004	0.004	-9999	-10000	0	0
NDC80	-0.36	0.32	-9999	-0.61	214	214
Cul3 protein complex	-0.013	0.065	-9999	-0.32	15	15
KIF2C	-0.14	0.11	-9999	-0.23	194	194
PEBP1	0.004	0.005	-9999	-10000	0	0
KIF20A	-0.3	0.26	-9999	-0.53	205	205
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.19	0.19	-9999	-0.37	190	190
SEPT1	0.008	0.027	-9999	-0.5	1	1
SMC2	0.01	0	-9999	-10000	0	0
SMC4	0.01	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.069	0.078	-9999	-10000	0	0
PSMA3	0.01	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.002	0.003	-9999	-10000	0	0
H3F3B	-0.094	0.1	-9999	-0.19	190	190
AURKB	-0.28	0.27	-9999	-0.53	190	190
AURKC	0.005	0.048	-9999	-0.51	3	3
CDCA8	-0.2	0.26	-9999	-0.54	132	132
cytokinesis	-0.25	0.22	-9999	-0.44	182	182
Aurora B/Septin1	-0.23	0.21	-9999	-0.42	173	173
AURKA	-0.11	0.22	-9999	-0.53	80	80
INCENP	0.002	0.007	-9999	-10000	0	0
KLHL13	-0.011	0.1	-9999	-0.51	14	14
BUB1	-0.15	0.25	-9999	-0.53	105	105
hSgo1/Aurora B/Survivin	-0.44	0.37	-9999	-0.68	231	231
EVI5	0.008	0.002	-9999	-10000	0	0
RhoA/GTP	-0.24	0.24	-9999	-0.49	142	142
SGOL1	-0.26	0.27	-9999	-0.52	179	179
CENPA	-0.18	0.17	-9999	-0.32	188	188
NCAPG	-0.24	0.26	-9999	-0.52	162	162
Aurora B/HC8 Proteasome	-0.19	0.19	-9999	-0.37	190	190
NCAPD2	0.008	0.028	-9999	-0.52	1	1
Aurora B/PP1-gamma	-0.19	0.19	-9999	-0.37	190	190
RHOA	0.01	0	-9999	-10000	0	0
NCAPH	-0.24	0.26	-9999	-0.52	163	163
NPM1	-0.09	0.084	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
KLHL9	0.007	0.039	-9999	-0.5	2	2
mitotic prometaphase	-0.009	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.19	0.19	-9999	-0.36	190	190
PPP1CC	0.01	0	-9999	-10000	0	0
Centraspindlin	-0.26	0.26	-9999	-0.49	174	174
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.09	0.084	-9999	-10000	0	0
MYLK	-0.1	0.12	-9999	-0.2	191	191
KIF23	-0.13	0.23	-9999	-0.53	89	89
VIM	-0.19	0.2	-9999	-0.37	190	190
RACGAP1	-0.001	0.057	-9999	-0.53	4	4
mitosis	0	0	-9999	-10000	0	0
NCL	-0.09	0.084	-9999	-10000	0	0
Chromosomal passenger complex	-0.21	0.2	-9999	-0.39	188	188
Chromosomal passenger complex/EVI5	-0.36	0.33	-9999	-0.65	187	187
TACC1	-0.011	0.1	-9999	-0.5	14	14
PPP2R5D	0.01	0	-9999	-10000	0	0
CUL3	0.01	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.36	0.51	-10000	0	-0.95	147	147
NCK1/PAK1/Dok-R	-0.19	0.21	-10000	0	-0.44	147	147
NCK1/Dok-R	-0.48	0.59	-10000	0	-1.1	147	147
PIK3CA	0.011	0.002	-10000	0	-10000	0	0
mol:beta2-estradiol	0.05	0.098	0.24	73	-10000	0	73
RELA	0.01	0	-10000	0	-10000	0	0
SHC1	0.006	0.005	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.004	0.21	0.24	70	-0.53	38	108
TNIP2	0.01	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.43	0.53	-10000	0	-1	147	147
FN1	0.004	0.054	-10000	0	-0.5	4	4
PLD2	-0.46	0.65	-10000	0	-1.2	147	147
PTPN11	0.01	0	-10000	0	-10000	0	0
GRB14	-0.029	0.14	-10000	0	-0.52	26	26
ELK1	-0.39	0.56	-10000	0	-1	147	147
GRB7	0.002	0.062	-10000	0	-0.52	5	5
PAK1	0.01	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.46	0.57	-10000	0	-1.1	147	147
CDKN1A	-0.24	0.35	-10000	0	-0.65	144	144
ITGA5	0.008	0.028	-10000	0	-0.52	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.48	0.59	-10000	0	-1.1	147	147
CRK	0.01	0	-10000	0	-10000	0	0
mol:NO	-0.25	0.37	-10000	0	-0.68	147	147
PLG	-0.46	0.65	-10000	0	-1.2	147	147
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.34	0.47	-10000	0	-0.89	147	147
GRB2	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.006	0.005	-10000	0	-10000	0	0
ANGPT2	-0.19	0.29	-10000	0	-0.63	88	88
BMX	-0.53	0.68	-10000	0	-1.3	147	147
ANGPT1	-0.26	0.51	-10000	0	-1.3	73	73
tube development	-0.28	0.39	-10000	0	-0.73	146	146
ANGPT4	-0.26	0.25	-10000	0	-0.5	181	181
response to hypoxia	-0.026	0.034	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.49	0.68	-10000	0	-1.2	147	147
alpha5/beta1 Integrin	-0.001	0.02	-10000	0	-0.37	1	1
FGF2	-0.054	0.16	-10000	0	-0.5	42	42
STAT5A (dimer)	-0.33	0.45	-10000	0	-0.85	146	146
mol:L-citrulline	-0.25	0.37	-10000	0	-0.68	147	147
AGTR1	-0.14	0.24	-10000	0	-0.5	105	105
MAPK14	-0.48	0.66	-10000	0	-1.2	147	147
Tie2/SHP2	-0.41	0.54	-10000	0	-1.1	128	128
TEK	-0.45	0.6	-10000	0	-1.2	128	128
RPS6KB1	-0.34	0.48	-10000	0	-0.9	147	147
Angiotensin II/AT1	-0.1	0.17	-10000	0	-0.36	105	105
Tie2/Ang1/GRB2	-0.47	0.67	-10000	0	-1.2	147	147
MAPK3	-0.4	0.58	-10000	0	-1.1	147	147
MAPK1	-0.4	0.58	-10000	0	-1.1	147	147
Tie2/Ang1/GRB7	-0.48	0.68	-10000	0	-1.2	147	147
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.46	0.65	-10000	0	-1.2	147	147
PI3K	-0.43	0.6	-10000	0	-1.1	147	147
FES	-0.48	0.65	-10000	0	-1.2	147	147
Crk/Dok-R	-0.48	0.59	-10000	0	-1.1	147	147
Tie2/Ang1/ABIN2	-0.47	0.67	-10000	0	-1.2	147	147
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.31	0.44	-10000	0	-0.83	147	147
STAT5A	0.008	0.027	-10000	0	-0.5	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.34	0.48	-10000	0	-0.9	147	147
Tie2/Ang2	-0.42	0.56	-10000	0	-1	146	146
Tie2/Ang1	-0.51	0.73	-10000	0	-1.3	147	147
FOXO1	-0.32	0.45	-10000	0	-0.84	147	147
ELF1	-0.022	0.05	-10000	0	-10000	0	0
ELF2	-0.46	0.65	-10000	0	-1.2	147	147
mol:Choline	-0.42	0.6	-10000	0	-1.1	147	147
cell migration	-0.1	0.12	-10000	0	-0.24	147	147
FYN	-0.33	0.45	-10000	0	-0.85	146	146
DOK2	-0.035	0.14	-10000	0	-0.5	31	31
negative regulation of cell cycle	-0.22	0.32	-10000	0	-0.58	144	144
ETS1	-0.037	0.094	-10000	0	-0.25	10	10
PXN	-0.27	0.4	-10000	0	-0.73	147	147
ITGB1	0.01	0	-10000	0	-10000	0	0
NOS3	-0.29	0.42	-10000	0	-0.78	147	147
RAC1	0.01	0	-10000	0	-10000	0	0
TNF	-0.062	0.15	-10000	0	-0.43	28	28
MAPKKK cascade	-0.42	0.6	-10000	0	-1.1	147	147
RASA1	0.01	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.49	0.67	-10000	0	-1.2	147	147
NCK1	0.01	0	-10000	0	-10000	0	0
vasculogenesis	-0.22	0.33	-10000	0	-0.6	147	147
mol:Phosphatidic acid	-0.42	0.6	-10000	0	-1.1	147	147
mol:Angiotensin II	0.001	0.002	-10000	0	-10000	0	0
mol:NADP	-0.25	0.37	-10000	0	-0.68	147	147
Rac1/GTP	-0.35	0.41	-10000	0	-0.83	147	147
MMP2	-0.46	0.65	-10000	0	-1.2	147	147

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.21	0.24	-10000	0	-0.64	62	62
IHH	-0.31	0.27	-10000	0	-0.54	202	202
SHH Np/Cholesterol/GAS1	-0.044	0.1	-10000	0	-0.28	55	55
LRPAP1	0.01	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.044	0.1	0.28	55	-10000	0	55
SMO/beta Arrestin2	-0.21	0.21	-10000	0	-0.5	73	73
SMO	-0.23	0.22	-10000	0	-0.53	73	73
AKT1	-0.092	0.1	-10000	0	-0.31	4	4
ARRB2	0.01	0	-10000	0	-10000	0	0
BOC	0.008	0.028	-10000	0	-0.52	1	1
ADRBK1	0.01	0	-10000	0	-10000	0	0
heart looping	-0.22	0.22	-10000	0	-0.52	73	73
STIL	-0.2	0.22	-10000	0	-0.52	83	83
DHH N/PTCH2	-0.024	0.09	-10000	0	-0.36	24	24
DHH N/PTCH1	-0.19	0.19	-10000	0	-0.48	67	67
PIK3CA	0.01	0	-10000	0	-10000	0	0
DHH	-0.024	0.13	-10000	0	-0.5	23	23
PTHLH	-0.28	0.29	-10000	0	-0.77	62	62
determination of left/right symmetry	-0.22	0.22	-10000	0	-0.52	73	73
PIK3R1	0.01	0	-10000	0	-10000	0	0
skeletal system development	-0.27	0.29	-10000	0	-0.76	62	62
IHH N/Hhip	-0.38	0.25	-10000	0	-0.5	272	272
DHH N/Hhip	-0.22	0.2	-10000	0	-0.38	204	204
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.22	0.22	-10000	0	-0.52	73	73
pancreas development	-0.28	0.25	-10000	0	-0.5	197	197
HHAT	0.007	0.039	-10000	0	-0.5	2	2
PI3K	0	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.006	0.089	-10000	0	-0.5	11	11
somite specification	-0.22	0.22	-10000	0	-0.52	73	73
SHH Np/Cholesterol/PTCH1	-0.18	0.19	-10000	0	-0.46	79	79
SHH Np/Cholesterol/PTCH2	-0.036	0.091	-10000	0	-0.27	48	48
SHH Np/Cholesterol/Megalin	-0.11	0.15	-10000	0	-0.3	126	126
SHH	-0.032	0.13	-10000	0	-0.36	47	47
catabolic process	-0.2	0.2	-10000	0	-0.51	55	55
SMO/Vitamin D3	-0.2	0.21	-10000	0	-0.5	79	79
SHH Np/Cholesterol/Hhip	-0.18	0.16	-10000	0	-0.3	214	214
LRP2	-0.13	0.23	-10000	0	-0.5	95	95
receptor-mediated endocytosis	-0.26	0.22	-10000	0	-0.54	106	106
SHH Np/Cholesterol/BOC	-0.036	0.091	-10000	0	-0.27	48	48
SHH Np/Cholesterol/CDO	-0.042	0.1	-10000	0	-0.28	53	53
mesenchymal cell differentiation	0.18	0.16	0.3	214	-10000	0	214
mol:Vitamin D3	-0.18	0.2	-10000	0	-0.46	79	79
IHH N/PTCH2	-0.18	0.17	-10000	0	-0.32	202	202
CDON	-0.002	0.076	-10000	0	-0.5	8	8
IHH N/PTCH1	-0.2	0.2	-10000	0	-0.51	55	55
Megalin/LRPAP1	-0.096	0.16	-10000	0	-0.36	95	95
PTCH2	0.008	0.027	-10000	0	-0.5	1	1
SHH Np/Cholesterol	-0.036	0.093	-10000	0	-0.27	47	47
PTCH1	-0.2	0.2	-10000	0	-0.51	55	55
HHIP	-0.28	0.26	-10000	0	-0.5	197	197

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.01	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.15	0.14	-9999	-0.28	192	192
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.044	0.04	-9999	-10000	0	0
AURKB	-0.28	0.26	-9999	-0.52	190	190
AURKC	0.005	0.048	-9999	-0.51	3	3

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.066	0.074	0.14	179	-10000	0	179
BUB1B	-0.13	0.12	-10000	0	-0.23	181	181
PLK1	-0.029	0.052	-10000	0	-0.12	74	74
PLK1S1	-0.011	0.027	-10000	0	-10000	0	0
KIF2A	-0.02	0.047	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	-0.029	0.052	-10000	0	-0.12	74	74
GOLGA2	0.01	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.24	0.26	-10000	0	-0.46	195	195
WEE1	-0.028	0.057	-10000	0	-10000	0	0
cytokinesis	-0.12	0.13	-10000	0	-0.25	158	158
PP2A-alpha B56	-0.018	0.036	-10000	0	-10000	0	0
AURKA	-0.023	0.047	-10000	0	-0.11	74	74
PICH/PLK1	-0.18	0.22	-10000	0	-0.41	152	152
CENPE	-0.087	0.16	-10000	0	-0.36	83	83
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.019	0.047	-10000	0	-10000	0	0
PPP2CA	0.01	0	-10000	0	-10000	0	0
FZR1	0.01	0	-10000	0	-10000	0	0
TPX2	-0.049	0.053	-10000	0	-0.11	111	111
PAK1	0.008	0.004	-10000	0	-10000	0	0
SPC24	-0.16	0.25	-10000	0	-0.52	116	116
FBXW11	0.01	0	-10000	0	-10000	0	0
CLSPN	-0.043	0.059	-10000	0	-0.13	82	82
GORASP1	0.01	0	-10000	0	-10000	0	0
metaphase	-0.002	0.005	-10000	0	-0.011	74	74
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.015	0.027	-10000	0	-0.059	68	68
G2 phase of mitotic cell cycle	-0.002	0.003	-10000	0	-10000	0	0
STAG2	0.01	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.002	0.011	-10000	0	-10000	0	0
spindle elongation	-0.029	0.052	-10000	0	-0.12	74	74
ODF2	0.007	0.004	-10000	0	-10000	0	0
BUB1	-0.027	0.043	-10000	0	-10000	0	0
TPT1	-0.011	0.027	-10000	0	-10000	0	0
CDC25C	-0.07	0.062	-10000	0	-0.14	91	91
CDC25B	0.008	0.003	-10000	0	-10000	0	0
SGOL1	-0.067	0.074	-10000	0	-0.14	179	179
RHOA	0.01	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.08	0.11	-10000	0	-0.24	112	112
CDC14B	0.007	0.004	-10000	0	-10000	0	0
CDC20	-0.31	0.26	-10000	0	-0.52	214	214
PLK1/PBIP1	-0.053	0.095	-10000	0	-0.34	30	30
mitosis	-0.004	0.008	0.02	12	-0.018	68	80
FBXO5	-0.02	0.045	-10000	0	-10000	0	0
CDC2	-0.003	0.006	-10000	0	-0.012	87	87
NDC80	-0.27	0.27	-10000	0	-0.52	185	185
metaphase plate congression	-0.017	0.034	-10000	0	-10000	0	0
ERCC6L	-0.17	0.2	-10000	0	-0.41	133	133
NLP/gamma Tubulin	-0.013	0.028	-10000	0	-0.095	1	1
microtubule cytoskeleton organization	-0.011	0.027	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	-0.001	0.002	-10000	0	-10000	0	0
PPP1R12A	0.009	0.001	-10000	0	-10000	0	0
interphase	-0.001	0.002	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.22	0.23	-10000	0	-0.39	205	205
GRASP65/GM130/RAB1/GTP/PLK1	-0.02	0.029	-10000	0	-10000	0	0
RAB1A	0.01	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.019	0.046	-10000	0	-10000	0	0
mitotic prometaphase	-0.003	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.043	0.037	-10000	0	-10000	0	0
microtubule-based process	-0.19	0.17	-10000	0	-0.33	205	205
Golgi organization	-0.029	0.052	-10000	0	-0.12	74	74
Cohesin/SA2	-0.031	0.039	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.3	0.26	-10000	0	-0.52	205	205
APC/C/CDC20	-0.2	0.18	-10000	0	-0.33	214	214
PPP2R1A	0.01	0	-10000	0	-10000	0	0
chromosome segregation	-0.052	0.093	-10000	0	-0.34	30	30
PRC1	-0.085	0.2	-10000	0	-0.52	63	63
ECT2	-0.04	0.1	-10000	0	-0.37	25	25
C13orf34	-0.018	0.044	-10000	0	-10000	0	0
NUDC	-0.017	0.034	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.13	0.12	-10000	0	-0.23	181	181
spindle assembly	-0.021	0.041	-10000	0	-0.09	62	62
spindle stabilization	-0.011	0.027	-10000	0	-10000	0	0
APC/C/HCDH1	0.011	0.006	-10000	0	-10000	0	0
MKLP2/PLK1	-0.19	0.18	-10000	0	-0.33	205	205
CCNB1	-0.17	0.25	-10000	0	-0.52	117	117
PPP1CB	0.009	0.001	-10000	0	-10000	0	0
BTRC	0.01	0	-10000	0	-10000	0	0
ROCK2	-0.01	0.035	-10000	0	-10000	0	0
TUBG1	-0.011	0.027	-10000	0	-0.11	1	1
G2/M transition of mitotic cell cycle	-0.08	0.11	-10000	0	-0.25	87	87
MLF1IP	-0.028	0.11	-10000	0	-0.39	30	30
INCENP	0.009	0.002	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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
IKK alpha homodimer	-0.19	0.14	-9999	-0.36	67	67
NF kappa B1 p50/RelA/I kappa B alpha	-0.17	0.12	-9999	-0.46	18	18
alphaV/beta3 Integrin/Osteopontin/Src	-0.27	0.16	-9999	-0.37	264	264
AP1	-0.18	0.13	-9999	-0.46	39	39
ILK	-0.2	0.15	-9999	-0.37	67	67
bone resorption	-0.17	0.11	-9999	-0.45	22	22
PTK2B	0.007	0.039	-9999	-0.5	2	2
PYK2/p130Cas	-0.19	0.12	-9999	-0.5	21	21
ITGAV	0.011	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.002	0.027	-9999	-0.36	2	2
alphaV/beta3 Integrin/Osteopontin	-0.24	0.15	-9999	-0.32	269	269
MAP3K1	-0.21	0.15	-9999	-0.37	67	67
JUN	0.007	0.039	-9999	-0.5	2	2
MAPK3	-0.2	0.15	-9999	-0.39	67	67
MAPK1	-0.2	0.15	-9999	-0.39	67	67
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
MAPK8	-0.19	0.14	-9999	-0.35	67	67
ITGB3	-0.024	0.13	-9999	-0.52	23	23
NFKBIA	-0.18	0.15	-9999	-0.38	67	67
FOS	-0.029	0.14	-9999	-0.5	27	27
CD44	0.007	0.039	-9999	-0.5	2	2
CHUK	0.01	0	-9999	-10000	0	0
PLAU	-0.19	0.18	-9999	-0.52	58	58
NF kappa B1 p50/RelA	-0.17	0.12	-9999	-0.48	18	18
BCAR1	0.008	0.027	-9999	-0.5	1	1
RELA	0.01	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.024	0.091	-9999	-0.37	23	23
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.21	0.15	-9999	-0.28	272	272
VAV3	-0.19	0.14	-9999	-0.35	70	70
MAP3K14	-0.21	0.16	-9999	-0.39	67	67
ROCK2	0.01	0	-9999	-10000	0	0
SPP1	-0.39	0.23	-9999	-0.52	264	264
RAC1	0.01	0	-9999	-10000	0	0
Rac1/GTP	-0.18	0.12	-9999	-0.48	21	21
MMP2	-0.14	0.13	-9999	-0.4	21	21

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.34	0.47	-9999	-1.1	70	70
HDAC7	0.007	0.007	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.28	0.37	-9999	-0.83	74	74
SMAD4	0.011	0.003	-9999	-10000	0	0
ID2	-0.34	0.47	-9999	-1.1	71	71
AP1	-0.031	0.1	-9999	-0.36	29	29
ABCG2	-0.36	0.5	-9999	-1.1	74	74
HIF1A	-0.042	0.071	-9999	-10000	0	0
TFF3	-0.39	0.52	-9999	-1.1	84	84
GATA2	-0.039	0.15	-9999	-0.51	32	32
AKT1	-0.046	0.08	-9999	-10000	0	0
response to hypoxia	-0.063	0.083	-9999	-0.25	7	7
MCL1	-0.34	0.47	-9999	-1.1	70	70
NDRG1	-0.34	0.47	-9999	-1.1	71	71
SERPINE1	-0.34	0.48	-9999	-1.1	73	73
FECH	-0.34	0.47	-9999	-1.1	70	70
FURIN	-0.35	0.48	-9999	-1.1	71	71
NCOA2	0.008	0.039	-9999	-0.5	2	2
EP300	-0.047	0.11	-9999	-0.35	9	9
HMOX1	-0.34	0.47	-9999	-1.1	71	71
BHLHE40	-0.34	0.47	-9999	-1.1	70	70
BHLHE41	-0.35	0.48	-9999	-1.1	73	73
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.04	0.069	-9999	-0.39	3	3
ENG	-0.012	0.1	-9999	-0.58	4	4
JUN	0.006	0.039	-9999	-0.51	2	2
RORA	-0.34	0.48	-9999	-1.1	72	72
ABCB1	-0.12	0.24	-9999	-1.2	15	15
TFRC	-0.34	0.48	-9999	-1.1	71	71
CXCR4	-0.34	0.47	-9999	-1.1	71	71
TF	-0.4	0.52	-9999	-1.1	84	84
CITED2	-0.34	0.47	-9999	-1.1	70	70
HIF1A/ARNT	-0.39	0.55	-9999	-1.2	79	79
LDHA	-0.048	0.06	-9999	-0.45	2	2
ETS1	-0.34	0.47	-9999	-1.1	70	70
PGK1	-0.34	0.47	-9999	-1.1	70	70
NOS2	-0.36	0.49	-9999	-1.1	79	79
ITGB2	-0.34	0.48	-9999	-1.1	71	71
ALDOA	-0.34	0.47	-9999	-1.1	71	71
Cbp/p300/CITED2	-0.34	0.49	-9999	-1.1	68	68
FOS	-0.031	0.14	-9999	-0.51	27	27
HK2	-0.34	0.47	-9999	-1.1	72	72
SP1	0.015	0.015	-9999	-10000	0	0
GCK	-0.11	0.27	-9999	-1.1	14	14
HK1	-0.34	0.47	-9999	-1.1	71	71
NPM1	-0.34	0.47	-9999	-1.1	71	71
EGLN1	-0.34	0.47	-9999	-1.1	70	70
CREB1	0.016	0.001	-9999	-10000	0	0
PGM1	-0.34	0.47	-9999	-1.1	70	70
SMAD3	0.011	0.003	-9999	-10000	0	0
EDN1	-0.19	0.43	-9999	-1.1	56	56
IGFBP1	-0.37	0.5	-9999	-1.1	78	78
VEGFA	-0.26	0.36	-9999	-0.79	59	59
HIF1A/JAB1	-0.026	0.032	-9999	-10000	0	0
CP	-0.46	0.53	-9999	-1.1	97	97
CXCL12	-0.35	0.49	-9999	-1.1	73	73
COPS5	0.01	0.001	-9999	-10000	0	0
SMAD3/SMAD4	0	0.003	-9999	-10000	0	0
BNIP3	-0.34	0.47	-9999	-1.1	70	70
EGLN3	-0.4	0.53	-9999	-1.1	89	89
CA9	-0.5	0.52	-9999	-1.1	103	103
TERT	-0.4	0.52	-9999	-1.2	80	80
ENO1	-0.34	0.47	-9999	-1.1	70	70
PFKL	-0.34	0.47	-9999	-1.1	70	70
NCOA1	0.01	0	-9999	-10000	0	0
ADM	-0.34	0.48	-9999	-1.1	70	70
ARNT	-0.042	0.071	-9999	-10000	0	0
HNF4A	-0.1	0.22	-9999	-0.52	75	75
ADFP	-0.35	0.47	-9999	-1	79	79
SLC2A1	-0.35	0.43	-9999	-0.9	87	87
LEP	-0.36	0.49	-9999	-1.1	77	77
HIF1A/ARNT/Cbp/p300	-0.3	0.38	-9999	-0.86	74	74
EPO	-0.15	0.26	-9999	-0.79	3	3
CREBBP	-0.047	0.11	-9999	-0.35	9	9
HIF1A/ARNT/Cbp/p300/HDAC7	-0.32	0.4	-9999	-0.92	70	70
PFKFB3	-0.34	0.47	-9999	-1.1	70	70
NT5E	-0.36	0.48	-9999	-1.1	78	78

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.042	0.19	0.26	1	-0.52	26	27
PTK2B	0.007	0.039	-10000	0	-0.5	2	2
mol:Ca2+	-0.048	0.28	-10000	0	-0.94	28	28
EDN1	-0.057	0.22	-10000	0	-0.53	52	52
EDN3	-0.13	0.23	-10000	0	-0.5	96	96
EDN2	-0.14	0.24	-10000	0	-0.52	98	98
HRAS/GDP	-0.073	0.2	-10000	0	-0.5	39	39
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.003	0.14	-10000	0	-0.39	20	20
ADCY4	-0.063	0.17	-10000	0	-0.49	29	29
ADCY5	-0.088	0.2	-10000	0	-0.52	42	42
ADCY6	-0.049	0.16	-10000	0	-0.48	24	24
ADCY7	-0.05	0.16	-10000	0	-0.48	25	25
ADCY1	-0.053	0.16	-10000	0	-0.48	27	27
ADCY2	-0.074	0.18	-10000	0	-0.49	35	35
ADCY3	-0.048	0.16	-10000	0	-0.48	23	23
ADCY8	-0.16	0.18	-10000	0	-0.45	62	62
ADCY9	-0.055	0.16	-10000	0	-0.49	25	25
arachidonic acid secretion	-0.068	0.21	-10000	0	-0.49	49	49
ETB receptor/Endothelin-1/Gq/GTP	-0.15	0.2	-10000	0	-0.36	113	113
GNAO1	0.005	0.048	-10000	0	-0.51	3	3
HRAS	0.009	0.002	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.035	0.22	0.23	123	-0.49	25	148
ETA receptor/Endothelin-1/Gs/GTP	0.026	0.22	0.22	121	-0.48	27	148
mol:GTP	0	0.005	-10000	0	-10000	0	0
COL3A1	-0.098	0.26	-10000	0	-0.57	48	48
EDNRB	-0.28	0.26	-10000	0	-0.5	196	196
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.051	0.22	-10000	0	-0.64	25	25
CYSLTR1	-0.052	0.22	-10000	0	-0.67	24	24
SLC9A1	-0.017	0.11	0.18	1	-0.3	20	21
mol:GDP	-0.085	0.22	-10000	0	-0.53	43	43
SLC9A3	-0.28	0.36	-10000	0	-0.54	201	201
RAF1	-0.088	0.22	-10000	0	-0.53	46	46
JUN	-0.015	0.19	-10000	0	-0.67	17	17
JAK2	-0.042	0.19	-10000	0	-0.53	25	25
mol:IP3	-0.088	0.18	-10000	0	-0.44	46	46
ETA receptor/Endothelin-1	-0.01	0.28	0.27	123	-0.52	43	166
PLCB1	0.008	0.028	-10000	0	-0.52	1	1
PLCB2	-0.002	0.077	-10000	0	-0.5	8	8
ETA receptor/Endothelin-3	-0.094	0.18	-10000	0	-0.37	98	98
FOS	-0.091	0.27	-10000	0	-0.89	31	31
Gai/GDP	-0.009	0.087	-10000	0	-0.58	3	3
CRK	0.01	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.14	0.25	-10000	0	-0.56	67	67
BCAR1	0.008	0.027	-10000	0	-0.5	1	1
PRKCB1	-0.085	0.18	-10000	0	-0.42	47	47
GNAQ	0.009	0.028	-10000	0	-0.51	1	1
GNAZ	-0.031	0.14	-10000	0	-0.5	28	28
GNAL	0.001	0.067	-10000	0	-0.51	6	6
Gs family/GDP	-0.11	0.17	-10000	0	-0.48	43	43
ETA receptor/Endothelin-1/Gq/GTP	-0.006	0.15	0.2	1	-0.37	30	31
MAPK14	-0.12	0.18	-10000	0	-0.44	52	52
TRPC6	-0.055	0.3	-10000	0	-1	28	28
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.007	0.039	-10000	0	-0.5	2	2
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.13	0.19	-10000	0	-0.39	78	78
ETB receptor/Endothelin-2	-0.29	0.24	-10000	0	-0.44	231	231
ETB receptor/Endothelin-3	-0.29	0.23	-10000	0	-0.43	236	236
ETB receptor/Endothelin-1	-0.24	0.26	-10000	0	-0.44	201	201
MAPK3	-0.095	0.27	-10000	0	-0.79	36	36
MAPK1	-0.095	0.27	-10000	0	-0.79	36	36
Rac1/GDP	-0.073	0.2	-10000	0	-0.51	37	37
cAMP biosynthetic process	-0.1	0.19	-10000	0	-0.5	45	45
MAPK8	-0.025	0.2	-10000	0	-0.59	30	30
SRC	0.01	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.14	0.18	-10000	0	-0.4	74	74
p130Cas/CRK/Src/PYK2	-0.083	0.23	-10000	0	-0.59	43	43
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.073	0.2	-10000	0	-0.5	39	39
COL1A2	-0.19	0.27	-10000	0	-0.62	74	74
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.099	0.19	-10000	0	-0.39	100	100
mol:DAG	-0.088	0.18	-10000	0	-0.44	46	46
MAP2K2	-0.087	0.23	-10000	0	-0.63	40	40
MAP2K1	-0.087	0.23	-10000	0	-0.63	40	40
EDNRA	0.01	0.11	-10000	0	-0.42	6	6
positive regulation of muscle contraction	-0.029	0.17	-10000	0	-0.48	22	22
Gq family/GDP	-0.075	0.17	-10000	0	-0.54	27	27
HRAS/GTP	-0.092	0.2	-10000	0	-0.5	43	43
PRKCH	-0.079	0.18	-10000	0	-0.49	31	31
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	-0.08	0.18	-10000	0	-0.5	32	32
PRKCB	-0.083	0.19	-10000	0	-0.53	32	32
PRKCE	-0.08	0.18	-10000	0	-0.5	32	32
PRKCD	-0.079	0.18	-10000	0	-0.5	31	31
PRKCG	-0.097	0.19	-10000	0	-0.48	43	43
regulation of vascular smooth muscle contraction	-0.11	0.32	-10000	0	-1	31	31
PRKCQ	-0.11	0.21	-10000	0	-0.47	64	64
PLA2G4A	-0.076	0.23	-10000	0	-0.54	49	49
GNA14	-0.007	0.095	-10000	0	-0.51	12	12
GNA15	0.01	0.004	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
GNA11	0.008	0.028	-10000	0	-0.5	1	1
Rac1/GTP	0.035	0.22	0.23	123	-0.5	23	146
MMP1	-0.24	0.2	-10000	0	-0.39	208	208

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.035	0.044	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.089	0.12	-9999	-0.36	24	24
JUN	-0.056	0.12	-9999	-0.35	21	21
HRAS	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.13	0.16	-9999	-0.31	146	146
RAP1A	0.01	0	-9999	-10000	0	0
FRS2	0.007	0.04	-9999	-0.52	2	2
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.13	0.16	-9999	-0.31	146	146
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.09	0.13	-9999	-0.28	114	114
RHOA	0.01	0	-9999	-10000	0	0
RAP1A/GTP	-0.11	0.15	-9999	-0.48	22	22
GRB7	0.002	0.062	-9999	-0.52	5	5
RET51/GFRalpha1/GDNF	-0.13	0.16	-9999	-0.31	146	146
MAPKKK cascade	-0.1	0.14	-9999	-0.44	25	25
BCAR1	0.008	0.027	-9999	-0.5	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.09	0.13	-9999	-0.28	114	114
lamellipodium assembly	-0.086	0.11	-9999	-0.34	24	24
RET51/GFRalpha1/GDNF/SHC	-0.13	0.16	-9999	-0.31	146	146
PIK3CA	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.09	0.13	-9999	-0.28	114	114
RET9/GFRalpha1/GDNF/Shank3	-0.095	0.14	-9999	-0.29	115	115
MAPK3	-0.085	0.15	-9999	-0.46	22	22
DOK1	0.01	0	-9999	-10000	0	0
DOK6	-0.038	0.15	-9999	-0.5	33	33
PXN	0.01	0	-9999	-10000	0	0
neurite development	-0.089	0.15	-9999	-0.39	36	36
DOK5	-0.073	0.19	-9999	-0.52	55	55
GFRA1	-0.15	0.24	-9999	-0.5	108	108
MAPK8	-0.064	0.12	-9999	-0.35	21	21
HRAS/GTP	-0.11	0.15	-9999	-0.48	22	22
tube development	-0.087	0.13	-9999	-0.4	16	16
MAPK1	-0.085	0.15	-9999	-0.46	22	22
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.059	0.12	-9999	-0.23	107	107
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
PDLIM7	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.14	0.18	-9999	-0.52	44	44
SHC1	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.13	0.16	-9999	-0.33	101	101
RET51/GFRalpha1/GDNF/Dok5	-0.17	0.19	-9999	-0.35	143	143
PRKCA	0.007	0.039	-9999	-0.5	2	2
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.082	0.14	-9999	-0.28	107	107
PIK3R1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.059	0.12	-9999	-0.24	107	107
RET51/GFRalpha1/GDNF/Grb7	-0.13	0.17	-9999	-0.31	149	149
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.067	0.19	-9999	-0.52	51	51
DOK4	0.01	0	-9999	-10000	0	0
JNK cascade	-0.055	0.12	-9999	-0.34	21	21
RET9/GFRalpha1/GDNF/FRS2	-0.091	0.13	-9999	-0.28	116	116
SHANK3	0	0.072	-9999	-0.5	7	7
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.058	0.12	-9999	-0.24	107	107
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.076	0.13	-9999	-0.28	63	63
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.075	0.13	-9999	-0.38	21	21
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.078	0.14	-9999	-0.26	109	109
PI3K	-0.096	0.19	-9999	-0.39	65	65
SOS1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.087	0.13	-9999	-0.4	16	16
GRB10	0.01	0	-9999	-10000	0	0
activation of MAPKK activity	-0.07	0.12	-9999	-0.35	21	21
RET51/GFRalpha1/GDNF/FRS2	-0.13	0.16	-9999	-0.31	148	148
GAB1	0.008	0.027	-9999	-0.5	1	1
IRS1	0.008	0.027	-9999	-0.5	1	1
IRS2	0.008	0.027	-9999	-0.5	1	1
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.079	0.14	-9999	-0.27	108	108
RET51/GFRalpha1/GDNF/PKC alpha	-0.13	0.17	-9999	-0.31	147	147
GRB2	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GDNF	-0.008	0.083	-9999	-0.52	9	9
RAC1	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.13	0.17	-9999	-0.31	146	146
Rac1/GTP	-0.1	0.14	-9999	-0.41	24	24
RET9/GFRalpha1/GDNF	-0.1	0.15	-9999	-0.31	114	114
GFRalpha1/GDNF	-0.12	0.18	-9999	-0.37	114	114

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.014	0.058	-9999	-0.26	19	19
RGS9BP	-0.065	0.18	-9999	-0.5	51	51
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.028	0.13	-9999	-0.52	22	22
mol:Na +	-0.16	0.18	-9999	-0.35	159	159
mol:ADP	-0.015	0.095	-9999	-0.37	23	23
GNAT2	0.007	0.028	-9999	-0.52	1	1
RGS9-1/Gbeta5/R9AP	-0.13	0.18	-9999	-0.33	140	140
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.002	0.024	-9999	-0.32	2	2
GRK7	0.005	0.028	-9999	-0.52	1	1
CNGB3	-0.088	0.2	-9999	-0.52	62	62
Cone Metarhodopsin II/X-Arrestin	-0.001	0.02	-9999	-0.38	1	1
mol:Ca2+	-0.16	0.19	-9999	-0.33	177	177
Cone PDE6	-0.11	0.15	-9999	-0.5	21	21
Cone Metarhodopsin II	-0.019	0.071	-9999	-0.29	23	23
Na + (4 Units)	-0.16	0.18	-9999	-0.33	177	177
GNAT2/GDP	-0.11	0.15	-9999	-0.48	23	23
GNB5	0.01	0	-9999	-10000	0	0
mol:GMP (4 units)	0.007	0.023	-9999	-0.28	2	2
Cone Transducin	-0.015	0.062	-9999	-0.28	19	19
SLC24A2	-0.038	0.15	-9999	-0.52	30	30
GNB3/GNGT2	-0.019	0.08	-9999	-0.36	18	18
GNB3	-0.007	0.092	-9999	-0.52	11	11
GNAT2/GTP	-0.001	0.02	-9999	-0.38	1	1
CNGA3	-0.16	0.25	-9999	-0.52	115	115
ARR3	0.001	0.028	-9999	-0.52	1	1
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.16	0.18	-9999	-0.35	159	159
mol:Pi	-0.13	0.17	-9999	-0.33	140	140
Cone CNG Channel	-0.13	0.15	-9999	-0.52	19	19
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.038	0.15	-9999	-0.52	30	30
RGS9	-0.15	0.24	-9999	-0.5	109	109
PDE6C	0.003	0.004	-9999	-10000	0	0
GNGT2	0	0.072	-9999	-0.5	7	7
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.001	0.028	-9999	-0.52	1	1

×

IL4-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.46	0.53	-10000	0	-1.2	89	89
STAT6 (cleaved dimer)	-0.5	0.5	-10000	0	-1.2	109	109
IGHG1	-0.15	0.17	-10000	0	-0.38	14	14
IGHG3	-0.45	0.51	-10000	0	-1.1	103	103
AKT1	-0.18	0.24	-10000	0	-0.84	7	7
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.13	0.2	-10000	0	-0.97	5	5
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.19	0.25	-10000	0	-0.93	7	7
THY1	-0.46	0.54	-10000	0	-1.2	90	90
MYB	0.004	0.055	-10000	0	-0.51	4	4
HMGA1	-0.054	0.17	-10000	0	-0.52	42	42
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.24	0.28	-10000	0	-0.63	67	67
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.2	0.25	-10000	0	-0.85	9	9
SP1	0.015	0.005	-10000	0	-10000	0	0
INPP5D	0.007	0.039	-10000	0	-0.5	2	2
SOCS5	0.021	0.014	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.48	0.49	-10000	0	-1.2	96	96
SOCS1	-0.27	0.34	-10000	0	-0.75	78	78
SOCS3	-0.2	0.26	-10000	0	-0.93	8	8
FCER2	-0.35	0.43	-10000	0	-0.99	72	72
PARP14	0.01	0.003	-10000	0	-10000	0	0
CCL17	-0.51	0.61	-10000	0	-1.4	95	95
GRB2	0.01	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.15	0.2	-10000	0	-0.73	6	6
T cell proliferation	-0.45	0.54	-10000	0	-1.2	88	88
IL4R/JAK1	-0.46	0.53	-10000	0	-1.2	88	88
EGR2	-0.48	0.57	-10000	0	-1.3	88	88
JAK2	-0.01	0.03	-10000	0	-10000	0	0
JAK3	0.014	0.004	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
JAK1	0.006	0.011	-10000	0	-10000	0	0
COL1A2	-0.14	0.2	-10000	0	-0.74	12	12
CCL26	-0.48	0.55	-10000	0	-1.3	91	91
IL4R	-0.49	0.57	-10000	0	-1.3	88	88
PTPN6	0.02	0.013	-10000	0	-10000	0	0
IL13RA2	-0.5	0.58	-10000	0	-1.3	98	98
IL13RA1	-0.01	0.03	-10000	0	-10000	0	0
IRF4	-0.11	0.25	-10000	0	-0.85	25	25
ARG1	-0.13	0.19	-10000	0	-0.72	17	17
CBL	-0.22	0.27	-10000	0	-0.61	53	53
GTF3A	0.005	0.034	-10000	0	-0.52	1	1
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.013	0.043	-10000	0	-10000	0	0
IRF4/BCL6	-0.12	0.21	-10000	0	-0.83	22	22
CD40LG	-0.012	0.12	-10000	0	-0.5	19	19
MAPK14	-0.22	0.27	-10000	0	-0.66	35	35
mitosis	-0.17	0.23	-10000	0	-0.78	7	7
STAT6	-0.54	0.64	-10000	0	-1.4	92	92
SPI1	-0.018	0.12	-10000	0	-0.5	21	21
RPS6KB1	-0.16	0.23	-10000	0	-0.74	7	7
STAT6 (dimer)	-0.54	0.64	-10000	0	-1.4	92	92
STAT6 (dimer)/PARP14	-0.5	0.58	-10000	0	-1.3	92	92
mast cell activation	0.01	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.2	0.26	-10000	0	-0.79	20	20
FRAP1	-0.18	0.24	-10000	0	-0.84	7	7
LTA	-0.46	0.53	-10000	0	-1.2	88	88
FES	0.008	0.027	-10000	0	-0.5	1	1
T-helper 1 cell differentiation	0.52	0.61	1.4	92	-10000	0	92
CCL11	-0.46	0.54	-10000	0	-1.2	92	92
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.18	0.24	-10000	0	-0.91	7	7
IL2RG	0.009	0.054	-10000	0	-0.49	4	4
IL10	-0.47	0.54	-10000	0	-1.2	90	90
IRS1	0.008	0.027	-10000	0	-0.5	1	1
IRS2	0.008	0.027	-10000	0	-0.5	1	1
IL4	-0.099	0.12	-10000	0	-10000	0	0
IL5	-0.46	0.53	-10000	0	-1.2	89	89
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.36	0.4	-10000	0	-0.91	88	88
COL1A1	-0.23	0.24	-10000	0	-0.62	56	56
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.47	0.55	-10000	0	-1.3	85	85
IL2R gamma/JAK3	0.011	0.039	-10000	0	-0.34	4	4
TFF3	-0.51	0.57	-10000	0	-1.3	95	95
ALOX15	-0.8	0.73	-10000	0	-1.4	193	193
MYBL1	-0.002	0.079	-10000	0	-0.52	8	8
T-helper 2 cell differentiation	-0.37	0.41	-10000	0	-0.93	91	91
SHC1	0.01	0	-10000	0	-10000	0	0
CEBPB	0.012	0.006	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.18	0.24	-10000	0	-0.9	7	7
mol:PI-3-4-5-P3	-0.18	0.24	-10000	0	-0.84	7	7
PI3K	-0.19	0.26	-10000	0	-0.91	7	7
DOK2	-0.035	0.14	-10000	0	-0.5	31	31
ETS1	0.02	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.14	0.19	-10000	0	-0.69	6	6
ITGB3	-0.47	0.54	-10000	0	-1.2	90	90
PIGR	-0.62	0.7	-10000	0	-1.5	122	122
IGHE	0.033	0.043	-10000	0	-10000	0	0
MAPKKK cascade	-0.14	0.19	-10000	0	-0.68	6	6
BCL6	0.009	0.002	-10000	0	-10000	0	0
OPRM1	-0.46	0.53	-10000	0	-1.2	88	88
RETNLB	-0.47	0.54	-10000	0	-1.2	87	87
SELP	-0.57	0.67	-10000	0	-1.5	104	104
AICDA	-0.48	0.55	-10000	0	-1.2	98	98

×

amb2 Integrin 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
alphaM/beta2 Integrin/proMMP-2	-0.022	0.096	-9999	-0.44	16	16
alphaM/beta2 Integrin/GPIbA	-0.028	0.1	-9999	-0.4	22	22
alphaM/beta2 Integrin/proMMP-9	-0.075	0.15	-9999	-0.34	75	75
PLAUR	0.01	0	-9999	-10000	0	0
HMGB1	0.006	0.01	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.023	0.1	-9999	-0.46	16	16
AGER	-0.48	0.13	-9999	-0.51	331	331
RAP1A	0.01	0	-9999	-10000	0	0
SELPLG	-0.006	0.089	-9999	-0.5	11	11
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.3	0.16	-9999	-0.52	89	89
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.081	0.2	-9999	-0.52	60	60
CYR61	-0.019	0.12	-9999	-0.5	20	20
TLN1	0.008	0.027	-9999	-0.5	1	1
Rap1/GTP	-0.082	0.14	-9999	-0.43	32	32
RHOA	0.01	0	-9999	-10000	0	0
P-selectin oligomer	-0.095	0.21	-9999	-0.5	72	72
MYH2	-0.15	0.2	-9999	-0.47	68	68
MST1R	0.005	0.048	-9999	-0.51	3	3
leukocyte activation during inflammatory response	-0.044	0.11	-9999	-0.31	47	47
APOB	-0.04	0.15	-9999	-0.52	33	33
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.01	0	-9999	-10000	0	0
JAM3	0.004	0.054	-9999	-0.5	4	4
GP1BA	0.001	0.067	-9999	-0.51	6	6
alphaM/beta2 Integrin/CTGF	-0.037	0.12	-9999	-0.4	31	31
alphaM/beta2 Integrin	-0.085	0.18	-9999	-0.44	44	44
JAM3 homodimer	0.004	0.054	-9999	-0.5	4	4
ICAM2	0.004	0.054	-9999	-0.5	4	4
ICAM1	0.001	0.066	-9999	-0.5	6	6
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.084	0.18	-9999	-0.44	44	44
cell adhesion	-0.027	0.1	-9999	-0.4	22	22
NFKB1	-0.3	0.22	-9999	-0.64	89	89
THY1	-0.005	0.088	-9999	-0.52	10	10
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.031	0.094	-9999	-0.32	35	35
alphaM/beta2 Integrin/LRP/tPA	-0.057	0.14	-9999	-0.35	54	54
IL6	-0.35	0.32	-9999	-0.86	92	92
ITGB2	-0.006	0.078	-9999	-0.52	8	8
elevation of cytosolic calcium ion concentration	-0.071	0.13	-9999	-0.3	79	79
alphaM/beta2 Integrin/JAM2/JAM3	-0.047	0.14	-9999	-0.47	24	24
JAM2	-0.04	0.15	-9999	-0.5	34	34
alphaM/beta2 Integrin/ICAM1	-0.031	0.11	-9999	-0.6	9	9
alphaM/beta2 Integrin/uPA/Plg	-0.08	0.14	-9999	-0.31	89	89
RhoA/GTP	-0.1	0.19	-9999	-0.48	43	43
positive regulation of phagocytosis	-0.077	0.16	-9999	-0.65	20	20
Ron/MSP	-0.016	0.074	-9999	-0.37	15	15
alphaM/beta2 Integrin/uPAR/uPA	-0.072	0.14	-9999	-0.3	79	79
alphaM/beta2 Integrin/uPAR	-0.022	0.096	-9999	-0.44	16	16
PLAU	-0.094	0.21	-9999	-0.52	69	69
PLAT	-0.06	0.18	-9999	-0.52	46	46
actin filament polymerization	-0.14	0.19	-9999	-0.45	68	68
MST1	-0.008	0.096	-9999	-0.52	12	12
alphaM/beta2 Integrin/lipoprotein(a)	-0.045	0.11	-9999	-0.32	47	47
TNF	-0.29	0.24	-9999	-0.63	89	89
RAP1B	0.01	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.082	0.15	-9999	-0.34	84	84
fibrinolysis	-0.08	0.14	-9999	-0.31	89	89
HCK	-0.011	0.1	-9999	-0.5	14	14
dendritic cell antigen processing and presentation	-0.084	0.18	-9999	-0.44	44	44
VTN	-0.082	0.2	-9999	-0.5	63	63
alphaM/beta2 Integrin/CYR61	-0.039	0.12	-9999	-0.4	33	33
LPA	0	0.04	-9999	-0.52	2	2
LRP1	0.004	0.054	-9999	-0.5	4	4
cell migration	-0.065	0.13	-9999	-0.3	75	75
FN1	0.004	0.054	-9999	-0.5	4	4
alphaM/beta2 Integrin/Thy1	-0.031	0.11	-9999	-0.39	26	26
MPO	0.001	0.067	-9999	-0.51	6	6
KNG1	-0.034	0.14	-9999	-0.52	26	26
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.089	0.18	-9999	-0.47	38	38
ELA2	0	0	-9999	-10000	0	0
PLG	-0.01	0.078	-9999	-0.52	8	8
CTGF	-0.016	0.11	-9999	-0.5	18	18
alphaM/beta2 Integrin/Hck	-0.033	0.14	-9999	-0.55	20	20
ITGAM	-0.016	0.11	-9999	-0.52	15	15
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.08	0.18	-9999	-0.36	76	76
HP	-0.13	0.23	-9999	-0.51	96	96
leukocyte adhesion	-0.28	0.18	-9999	-0.48	115	115
SELP	-0.095	0.21	-9999	-0.5	72	72

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.089	0.31	-9999	-1	33	33
MKNK1	0.01	0	-9999	-10000	0	0
MAPK14	-0.027	0.12	-9999	-0.43	5	5
ATF2/c-Jun	-0.011	0.11	-9999	-0.54	6	6
MAPK11	-0.032	0.13	-9999	-0.5	8	8
MITF	-0.03	0.15	-9999	-0.36	58	58
MAPKAPK5	-0.027	0.14	-9999	-0.34	58	58
KRT8	-0.029	0.15	-9999	-0.35	58	58
MAPKAPK3	0.01	0	-9999	-10000	0	0
MAPKAPK2	0.01	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.044	0.18	-9999	-0.43	58	58
CEBPB	-0.027	0.14	-9999	-0.34	58	58
SLC9A1	-0.027	0.14	-9999	-0.34	58	58
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.022	0.14	-9999	-0.34	58	58
p38alpha-beta/MNK1	-0.026	0.14	-9999	-0.33	58	58
JUN	-0.011	0.11	-9999	-0.54	6	6
PPARGC1A	-0.11	0.22	-9999	-0.36	126	126
USF1	-0.027	0.14	-9999	-0.34	58	58
RAB5/GDP/GDI1	-0.042	0.093	-9999	-0.37	8	8
NOS2	-0.082	0.3	-9999	-1	29	29
DDIT3	-0.027	0.14	-9999	-0.34	58	58
RAB5A	0.01	0	-9999	-10000	0	0
HSPB1	-0.016	0.12	-9999	-0.45	9	9
p38alpha-beta/HBP1	-0.026	0.14	-9999	-0.51	8	8
CREB1	-0.028	0.16	-9999	-0.37	58	58
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.016	0.12	-9999	-0.45	8	8
RPS6KA4	-0.027	0.14	-9999	-0.34	58	58
PLA2G4A	-0.065	0.17	-9999	-0.52	15	15
GDI1	-0.027	0.14	-9999	-0.34	58	58
TP53	-0.037	0.18	-9999	-0.42	58	58
RPS6KA5	-0.029	0.15	-9999	-0.35	59	59
ESR1	-0.046	0.18	-9999	-0.39	60	60
HBP1	0.01	0	-9999	-10000	0	0
MEF2C	-0.027	0.14	-9999	-0.34	58	58
MEF2A	-0.027	0.14	-9999	-0.34	58	58
EIF4EBP1	-0.029	0.16	-9999	-0.37	58	58
KRT19	-0.03	0.15	-9999	-0.34	58	58
ELK4	-0.027	0.14	-9999	-0.34	58	58
ATF6	-0.027	0.14	-9999	-0.34	58	58
ATF1	-0.028	0.16	-9999	-0.37	58	58
p38alpha-beta/MAPKAPK2	-0.026	0.14	-9999	-0.51	8	8
p38alpha-beta/MAPKAPK3	-0.026	0.14	-9999	-0.51	8	8

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	-0.082	0.14	-9999	-0.52	13	13
SMAD6-7/SMURF1	-0.042	0.1	-9999	-0.3	49	49
NOG	-0.033	0.14	-9999	-0.51	29	29
SMAD9	-0.11	0.2	-9999	-0.48	72	72
SMAD4	0.01	0	-9999	-10000	0	0
SMAD5	-0.027	0.11	-9999	-0.36	16	16
BMP7/USAG1	-0.28	0.2	-9999	-0.39	253	253
SMAD5/SKI	-0.02	0.11	-9999	-0.44	6	6
SMAD1	0.022	0.03	-9999	-10000	0	0
BMP2	-0.062	0.18	-9999	-0.5	49	49
SMAD1/SMAD1/SMAD4	-0.028	0.069	-9999	-0.41	1	1
BMPR1A	0.01	0	-9999	-10000	0	0
BMPR1B	-0.041	0.15	-9999	-0.5	35	35
BMPR1A-1B/BAMBI	-0.042	0.11	-9999	-0.31	48	48
AHSG	-0.039	0.14	-9999	-0.52	29	29
CER1	-0.003	0.048	-9999	-0.52	3	3
BMP2-4/CER1	-0.052	0.12	-9999	-0.32	57	57
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.017	0.12	-9999	-0.4	14	14
BMP2-4 (homodimer)	-0.059	0.14	-9999	-0.38	55	55
RGMB	0.01	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.069	0.13	-9999	-0.53	12	12
RGMA	-0.001	0.073	-9999	-0.52	7	7
SMURF1	0.01	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.024	0.11	-9999	-0.37	14	14
BMP2-4/USAG1	-0.24	0.18	-9999	-0.34	248	248
SMAD6/SMURF1/SMAD5	-0.02	0.11	-9999	-0.44	6	6
SOSTDC1	-0.33	0.24	-9999	-0.5	233	233
BMP7/BMPR2/BMPR1A-1B	-0.063	0.12	-9999	-0.53	5	5
SKI	0.01	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.075	0.19	-9999	-0.5	58	58
HFE2	-0.004	0.068	-9999	-0.52	6	6
ZFYVE16	0.01	0	-9999	-10000	0	0
MAP3K7	0.01	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.058	0.13	-9999	-0.33	62	62
SMAD5/SMAD5/SMAD4	-0.02	0.11	-9999	-0.44	6	6
MAPK1	0.01	0	-9999	-10000	0	0
TAK1/TAB family	-0.04	0.081	-9999	-0.38	8	8
BMP7 (homodimer)	-0.064	0.18	-9999	-0.51	50	50
NUP214	0.01	0	-9999	-10000	0	0
BMP6/FETUA	-0.089	0.16	-9999	-0.38	83	83
SMAD1/SKI	0.027	0.028	-9999	-10000	0	0
SMAD6	-0.062	0.18	-9999	-0.5	49	49
CTDSP2	0.01	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.075	0.15	-9999	-0.33	79	79
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.38	0.24	-9999	-0.52	257	257
BMPR2 (homodimer)	0.01	0	-9999	-10000	0	0
GADD34/PP1CA	-0.002	0.022	-9999	-0.29	2	2
BMPR1A-1B (homodimer)	-0.035	0.11	-9999	-0.36	35	35
CHRDL1	-0.17	0.24	-9999	-0.5	121	121
ENDOFIN/SMAD1	0.027	0.028	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.032	0.078	-9999	-0.47	1	1
SMAD6/SMURF1	0.01	0	-9999	-10000	0	0
BAMBI	-0.013	0.11	-9999	-0.52	15	15
SMURF2	0.01	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.15	0.2	-9999	-0.37	142	142
BMP2-4/GREM1	-0.27	0.18	-9999	-0.35	272	272
SMAD7	0.008	0.027	-9999	-0.5	1	1
SMAD8A/SMAD8A/SMAD4	-0.084	0.19	-9999	-0.45	72	72
SMAD1/SMAD6	0.027	0.028	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.064	0.18	-9999	-0.51	50	50
BMP6	-0.075	0.19	-9999	-0.5	58	58
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.019	0.11	-9999	-0.41	10	10
PPM1A	0.01	0	-9999	-10000	0	0
SMAD1/SMURF2	0.027	0.028	-9999	-10000	0	0
SMAD7/SMURF1	-0.001	0.019	-9999	-0.36	1	1
CTDSPL	0.01	0	-9999	-10000	0	0
PPP1CA	0.01	0	-9999	-10000	0	0
XIAP	0.01	0	-9999	-10000	0	0
CTDSP1	0.01	0	-9999	-10000	0	0
PPP1R15A	0.007	0.039	-9999	-0.5	2	2
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.039	0.13	-9999	-0.4	23	23
CHRD	-0.005	0.088	-9999	-0.52	10	10
BMPR2	0.01	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.03	0.12	-9999	-0.41	14	14
BMP4	-0.005	0.086	-9999	-0.51	10	10
FST	-0.04	0.15	-9999	-0.52	33	33
BMP2-4/NOG	-0.073	0.15	-9999	-0.35	74	74
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.058	0.11	-9999	-0.5	5	5

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.22	0.32	-10000	0	-0.83	36	36
PCK1	-0.18	0.23	-10000	0	-0.68	27	27
HNF4A	-0.41	0.49	-10000	0	-1	107	107
KCNJ11	-0.19	0.33	-10000	0	-0.87	39	39
AKT1	-0.075	0.14	-10000	0	-0.4	7	7
response to starvation	-0.028	0.046	-10000	0	-10000	0	0
DLK1	-0.21	0.33	-10000	0	-0.85	37	37
NKX2-1	-0.14	0.4	-10000	0	-1.4	30	30
ACADM	-0.22	0.32	-10000	0	-0.83	36	36
TAT	-0.17	0.22	-10000	0	-0.7	17	17
CEBPB	0.009	0.005	-10000	0	-10000	0	0
CEBPA	-0.02	0.12	-10000	0	-0.51	20	20
TTR	-0.2	0.25	-10000	0	-0.71	44	44
PKLR	-0.22	0.32	-10000	0	-0.86	37	37
APOA1	-0.51	0.63	-10000	0	-1.3	122	122
CPT1C	-0.23	0.33	-10000	0	-0.86	37	37
ALAS1	-0.076	0.16	-10000	0	-10000	0	0
TFRC	-0.17	0.27	-10000	0	-0.9	16	16
FOXF1	-0.059	0.18	0.22	2	-0.48	50	52
NF1	0.016	0	-10000	0	-10000	0	0
HNF1A (dimer)	-0.1	0.23	-10000	0	-0.58	64	64
CPT1A	-0.22	0.32	-10000	0	-0.83	36	36
HMGCS1	-0.22	0.32	-10000	0	-0.82	38	38
NR3C1	0.005	0.032	-10000	0	-10000	0	0
CPT1B	-0.22	0.32	-10000	0	-0.83	39	39
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0	0.025	-10000	0	-10000	0	0
GCK	-0.24	0.34	-10000	0	-0.85	48	48
CREB1	0.005	0.021	-10000	0	-10000	0	0
IGFBP1	-0.13	0.19	-10000	0	-0.57	23	23
PDX1	-0.16	0.26	-10000	0	-0.66	46	46
UCP2	-0.22	0.32	-10000	0	-0.83	36	36
ALDOB	-0.2	0.34	-10000	0	-0.83	45	45
AFP	-0.076	0.15	-10000	0	-0.54	16	16
BDH1	-0.22	0.32	-10000	0	-0.84	36	36
HADH	-0.18	0.31	-10000	0	-0.83	31	31
F2	-0.33	0.43	-10000	0	-1	58	58
HNF1A	-0.1	0.23	-10000	0	-0.58	64	64
G6PC	-0.083	0.16	-10000	0	-0.6	12	12
SLC2A2	-0.15	0.24	-10000	0	-0.67	23	23
INS	0	0.028	-10000	0	-10000	0	0
FOXA1	-0.016	0.12	0.26	5	-0.55	10	15
FOXA3	-0.17	0.28	-10000	0	-0.59	98	98
FOXA2	-0.22	0.36	-10000	0	-0.89	40	40
ABCC8	-0.24	0.38	-10000	0	-0.9	58	58
ALB	-0.088	0.17	-10000	0	-0.47	32	32

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.008	0.028	-9999	-0.52	1	1
LAT2	-0.089	0.2	-9999	-0.48	53	53
AP1	-0.13	0.21	-9999	-0.5	68	68
mol:PIP3	-0.095	0.22	-9999	-0.5	60	60
IKBKB	-0.04	0.12	-9999	-0.27	54	54
AKT1	-0.061	0.16	-9999	-0.38	51	51
IKBKG	-0.04	0.12	-9999	-0.27	54	54
MS4A2	-0.11	0.22	-9999	-0.51	81	81
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.008	0.003	-9999	-10000	0	0
MAP3K1	-0.063	0.18	-9999	-0.4	60	60
mol:Ca2+	-0.067	0.17	-9999	-0.37	60	60
LYN	0.008	0.005	-9999	-10000	0	0
CBLB	-0.085	0.19	-9999	-0.45	53	53
SHC1	0.01	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.024	0.077	-9999	-0.27	32	32
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.007	0.039	-9999	-0.5	2	2
PLD2	-0.094	0.18	-9999	-0.47	50	50
PTPN13	-0.11	0.22	-9999	-0.51	64	64
PTPN11	0.007	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.042	0.15	-9999	-0.32	51	51
SYK	0.004	0.05	-9999	-0.53	3	3
GRB2	0.009	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.13	0.2	-9999	-0.52	60	60
LAT	-0.085	0.19	-9999	-0.46	52	52
PAK2	-0.077	0.2	-9999	-0.46	60	60
NFATC2	-0.065	0.15	-9999	-0.76	12	12
HRAS	-0.092	0.22	-9999	-0.51	60	60
GAB2	0.004	0.054	-9999	-0.5	4	4
PLA2G1B	-0.002	0.032	-9999	-10000	0	0
Fc epsilon R1	-0.15	0.21	-9999	-0.4	130	130
Antigen/IgE/Fc epsilon R1	-0.13	0.2	-9999	-0.36	130	130
mol:GDP	-0.1	0.24	-9999	-0.54	62	62
JUN	0.007	0.039	-9999	-0.5	2	2
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.008	0.003	-9999	-10000	0	0
FOS	-0.03	0.14	-9999	-0.5	27	27
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.12	0.18	-9999	-0.39	85	85
CHUK	-0.04	0.12	-9999	-0.26	58	58
KLRG1	-0.08	0.18	-9999	-0.43	51	51
VAV1	-0.088	0.2	-9999	-0.47	53	53
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.085	0.19	-9999	-0.45	53	53
negative regulation of mast cell degranulation	-0.071	0.17	-9999	-0.4	51	51
BTK	-0.14	0.25	-9999	-0.48	89	89
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.11	0.22	-9999	-0.58	50	50
GAB2/PI3K/SHP2	-0.1	0.15	-9999	-0.42	51	51
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.096	0.2	-9999	-0.5	51	51
RAF1	0.02	0.023	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.12	0.18	-9999	-0.5	50	50
FCER1G	-0.002	0.088	-9999	-0.51	10	10
FCER1A	-0.13	0.23	-9999	-0.52	92	92
Antigen/IgE/Fc epsilon R1/Fyn	-0.12	0.18	-9999	-0.5	50	50
MAPK3	0.028	0.019	-9999	-10000	0	0
MAPK1	0.028	0.019	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
MAPK8	-0.011	0.06	-9999	-10000	0	0
DUSP1	-0.037	0.15	-9999	-0.5	32	32
NF-kappa-B/RelA	-0.042	0.06	-9999	-0.22	6	6
actin cytoskeleton reorganization	-0.092	0.2	-9999	-0.48	52	52
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.11	0.18	-9999	-0.45	58	58
FER	-0.085	0.19	-9999	-0.45	53	53
RELA	0.01	0	-9999	-10000	0	0
ITK	-0.037	0.087	-9999	-0.52	9	9
SOS1	0.01	0	-9999	-10000	0	0
PLCG1	-0.1	0.24	-9999	-0.55	60	60
cytokine secretion	-0.031	0.044	-9999	-10000	0	0
SPHK1	-0.087	0.19	-9999	-0.45	55	55
PTK2	-0.097	0.21	-9999	-0.51	52	52
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.21	-9999	-0.54	60	60
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.09	0.22	-9999	-0.49	61	61
MAP2K2	0.025	0.02	-9999	-10000	0	0
MAP2K1	0.025	0.02	-9999	-10000	0	0
MAP2K7	0.01	0	-9999	-10000	0	0
KLRG1/SHP2	-0.091	0.15	-9999	-0.39	51	51
MAP2K4	0.011	0.011	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.13	0.19	-9999	-0.53	50	50
mol:Choline	-0.092	0.18	-9999	-0.46	50	50
SHC/Grb2/SOS1	-0.098	0.16	-9999	-0.42	51	51
FYN	0.01	0	-9999	-10000	0	0
DOK1	0.01	0	-9999	-10000	0	0
PXN	-0.084	0.19	-9999	-0.47	51	51
HCLS1	-0.087	0.19	-9999	-0.46	53	53
PRKCB	-0.067	0.17	-9999	-0.37	60	60
FCGR2B	0.01	0	-9999	-10000	0	0
IGHE	-0.002	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.072	0.17	-9999	-0.41	51	51
LCP2	0.006	0.039	-9999	-0.51	2	2
PLA2G4A	-0.13	0.22	-9999	-0.5	69	69
RASA1	0.01	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.092	0.18	-9999	-0.46	50	50
IKK complex	-0.018	0.097	-9999	-0.23	15	15
WIPF1	0.01	0	-9999	-10000	0	0

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.023	0.12	-10000	0	-0.48	25	25
CDKN2C	0.022	0.035	-10000	0	-0.46	1	1
CDKN2A	-0.15	0.25	-10000	0	-0.54	104	104
CCND2	0.042	0.065	0.2	25	-0.12	4	29
RB1	-0.046	0.067	-10000	0	-0.2	26	26
CDK4	0.049	0.07	0.2	26	-10000	0	26
CDK6	0.047	0.07	0.22	25	-10000	0	25
G1/S progression	0.037	0.073	0.2	26	-10000	0	26

×

Visual signal transduction: Rods

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
mol:K +	0.01	0	-9999	-10000	0	0
GNAT1/GTP	-0.008	0.053	-9999	-0.38	7	7
Metarhodopsin II/Arrestin	0	0	-9999	-10000	0	0
PDE6G/GNAT1/GTP	-0.011	0.065	-9999	-0.37	10	10
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.008	0.073	-9999	-0.52	7	7
GRK1	-0.028	0.13	-9999	-0.52	22	22
CNG Channel	-0.11	0.15	-9999	-0.51	26	26
mol:Na +	-0.12	0.16	-9999	-0.49	30	30
mol:ADP	-0.028	0.13	-9999	-0.52	22	22
RGS9-1/Gbeta5/R9AP	-0.13	0.18	-9999	-0.33	140	140
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.13	0.16	-9999	-0.5	30	30
CNGB1	-0.087	0.2	-9999	-0.52	64	64
RDH5	-0.001	0.074	-9999	-0.52	7	7
SAG	0.002	0.004	-9999	-10000	0	0
mol:Ca2+	-0.1	0.16	-9999	-0.47	30	30
Na + (4 Units)	-0.12	0.14	-9999	-0.46	30	30
RGS9	-0.15	0.24	-9999	-0.5	109	109
GNB1/GNGT1	-0.078	0.15	-9999	-0.37	74	74
GNAT1/GDP	-0.12	0.15	-9999	-0.29	144	144
GUCY2D	0.001	0.068	-9999	-0.51	6	6
GNGT1	-0.1	0.22	-9999	-0.52	74	74
GUCY2F	0.002	0.004	-9999	-10000	0	0
GNB5	0.01	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.013	0.095	-9999	-0.41	5	5
mol:11-cis-retinal	-0.001	0.074	-9999	-0.52	7	7
mol:cGMP	-0.055	0.11	-9999	-0.27	66	66
GNB1	0.01	0	-9999	-10000	0	0
Rhodopsin	-0.007	0.052	-9999	-0.38	7	7
SLC24A1	0.01	0	-9999	-10000	0	0
CNGA1	-0.073	0.19	-9999	-0.52	55	55
Metarhodopsin II	-0.018	0.07	-9999	-0.29	22	22
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.058	0.12	-9999	-0.29	71	71
RGS9BP	-0.065	0.18	-9999	-0.5	51	51
Metarhodopsin II/Transducin	-0.023	0.064	-9999	-0.23	2	2
GCAP Family/Ca ++	-0.055	0.12	-9999	-0.3	65	65
PDE6A/B	-0.031	0.1	-9999	-0.36	31	31
mol:Pi	-0.13	0.17	-9999	-0.33	140	140
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.065	0.12	-9999	-0.29	79	79
PDE6B	0.004	0.054	-9999	-0.5	4	4
PDE6A	-0.03	0.14	-9999	-0.5	27	27
PDE6G	0.002	0.062	-9999	-0.51	5	5
RHO	0.004	0.005	-9999	-10000	0	0
PDE6	-0.13	0.17	-9999	-0.49	39	39
GUCA1A	-0.087	0.2	-9999	-0.52	63	63
GC2/GCAP Family	-0.055	0.12	-9999	-0.3	65	65
GUCA1C	0	0.002	-9999	-10000	0	0
GUCA1B	0.002	0.062	-9999	-0.52	5	5

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.11	0.18	-10000	0	-0.38	104	104
TP53	-0.027	0.046	0.18	1	-10000	0	1
Senescence	-0.027	0.046	0.18	1	-10000	0	1
Apoptosis	-0.027	0.046	0.18	1	-10000	0	1
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.053	0.09	0.19	103	-0.34	2	105
MDM4	0.01	0	-10000	0	-10000	0	0

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.03	0.084	0.31	6	-10000	0	6
SMARCC2	0.011	0.005	-10000	0	-10000	0	0
SMARCC1	0.011	0.005	-10000	0	-10000	0	0
TBX21	-0.11	0.22	-10000	0	-0.61	38	38
SUMO2	0.009	0.006	-10000	0	-10000	0	0
STAT1 (dimer)	0.016	0	-10000	0	-10000	0	0
FKBP4	0.008	0.028	-10000	0	-0.52	1	1
FKBP5	0.008	0.027	-10000	0	-0.5	1	1
GR alpha/HSP90/FKBP51/HSP90	0.091	0.1	0.28	41	-10000	0	41
PRL	-0.069	0.13	-10000	0	-0.57	4	4
cortisol/GR alpha (dimer)/TIF2	0.21	0.26	0.53	103	-10000	0	103
RELA	-0.028	0.085	-10000	0	-0.27	2	2
FGG	-0.012	0.33	0.47	43	-0.48	81	124
GR beta/TIF2	0.095	0.12	0.31	44	-10000	0	44
IFNG	-0.22	0.26	-10000	0	-0.65	63	63
apoptosis	-0.018	0.16	0.46	10	-0.58	11	21
CREB1	-0.007	0.051	-10000	0	-10000	0	0
histone acetylation	-0.031	0.14	0.28	6	-0.36	24	30
BGLAP	-0.063	0.13	-10000	0	-0.51	6	6
GR/PKAc	0.089	0.098	0.27	39	-10000	0	39
NF kappa B1 p50/RelA	-0.048	0.15	-10000	0	-0.44	14	14
SMARCD1	0.011	0.005	-10000	0	-10000	0	0
MDM2	0.074	0.096	0.26	42	-0.24	1	43
GATA3	0.012	0.04	-10000	0	-0.51	2	2
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.12	0.31	-10000	0	-0.95	33	33
GSK3B	0.009	0.006	-10000	0	-10000	0	0
NR1I3	0.005	0.15	0.48	7	-0.56	5	12
CSN2	0.12	0.16	0.39	42	-10000	0	42
BRG1/BAF155/BAF170/BAF60A	0.013	0.026	-10000	0	-0.27	1	1
NFATC1	0.007	0.047	-10000	0	-0.5	3	3
POU2F1	0.009	0.016	-10000	0	-10000	0	0
CDKN1A	0.025	0.071	-10000	0	-1.3	1	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.006	-10000	0	-10000	0	0
SFN	-0.002	0.079	-10000	0	-0.52	8	8
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.085	0.1	0.28	36	-10000	0	36
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.031	0.24	0.45	8	-0.81	26	34
JUN	-0.17	0.18	-10000	0	-0.45	66	66
IL4	-0.079	0.14	-10000	0	-0.57	10	10
CDK5R1	-0.006	0.088	-10000	0	-0.52	10	10
PRKACA	0.01	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.13	0.23	0.21	1	-0.48	67	68
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.092	0.098	0.28	37	-10000	0	37
cortisol/GR alpha (monomer)	0.25	0.31	0.63	106	-10000	0	106
NCOA2	0.007	0.039	-10000	0	-0.5	2	2
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.08	0.15	-10000	0	-0.56	27	27
AP-1/NFAT1-c-4	-0.28	0.28	-10000	0	-0.64	107	107
AFP	-0.14	0.17	-10000	0	-0.69	10	10
SUV420H1	0.01	0	-10000	0	-10000	0	0
IRF1	0.13	0.15	0.4	42	-10000	0	42
TP53	0.026	0.027	-10000	0	-0.48	1	1
PPP5C	0.01	0	-10000	0	-10000	0	0
KRT17	-0.25	0.32	-10000	0	-0.7	87	87
KRT14	-0.18	0.2	-10000	0	-0.56	31	31
TBP	0.017	0	-10000	0	-10000	0	0
CREBBP	0.048	0.064	-10000	0	-0.26	1	1
HDAC1	0.007	0.004	-10000	0	-10000	0	0
HDAC2	0.012	0.023	-10000	0	-10000	0	0
AP-1	-0.28	0.28	-10000	0	-0.64	107	107
MAPK14	0.009	0.006	-10000	0	-10000	0	0
MAPK10	-0.048	0.16	-10000	0	-0.5	39	39
MAPK11	0.005	0.048	-10000	0	-0.51	3	3
KRT5	-0.39	0.5	-10000	0	-1.1	100	100
interleukin-1 receptor activity	0.005	0.023	-10000	0	-10000	0	0
NCOA1	0.012	0.001	-10000	0	-10000	0	0
STAT1	0.016	0	-10000	0	-10000	0	0
CGA	-0.12	0.19	-10000	0	-0.5	45	45
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.12	0.18	0.45	55	-10000	0	55
MAPK3	0.009	0.006	-10000	0	-10000	0	0
MAPK1	0.009	0.006	-10000	0	-10000	0	0
ICAM1	-0.13	0.24	-10000	0	-0.75	26	26
NFKB1	-0.028	0.085	-10000	0	-0.26	6	6
MAPK8	-0.15	0.17	-10000	0	-0.4	71	71
MAPK9	0.009	0.006	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.022	0.17	0.47	10	-0.61	11	21
BAX	0.028	0.023	-10000	0	-10000	0	0
POMC	-0.19	0.31	-10000	0	-0.77	50	50
EP300	0.048	0.065	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.23	0.26	0.55	99	-10000	0	99
proteasomal ubiquitin-dependent protein catabolic process	0.051	0.074	0.24	10	-0.21	1	11
SGK1	0.094	0.1	-10000	0	-1.2	1	1
IL13	-0.16	0.19	-10000	0	-0.63	19	19
IL6	-0.28	0.43	-10000	0	-0.95	94	94
PRKACG	0.002	0.004	-10000	0	-10000	0	0
IL5	-0.14	0.16	-10000	0	-0.55	16	16
IL2	-0.2	0.23	-10000	0	-0.61	56	56
CDK5	0.009	0.004	-10000	0	-10000	0	0
PRKACB	0.008	0.028	-10000	0	-0.52	1	1
HSP90AA1	0.01	0	-10000	0	-10000	0	0
IL8	-0.13	0.22	-10000	0	-0.63	36	36
CDK5R1/CDK5	-0.009	0.063	-10000	0	-0.37	10	10
NF kappa B1 p50/RelA/PKAc	-0.018	0.11	-10000	0	-0.36	9	9
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.21	0.24	0.51	98	-10000	0	98
SMARCA4	0.01	0.028	-10000	0	-0.5	1	1
chromatin remodeling	0.14	0.14	0.37	56	-10000	0	56
NF kappa B1 p50/RelA/Cbp	0.016	0.14	0.37	3	-0.41	6	9
JUN (dimer)	-0.17	0.18	-10000	0	-0.45	66	66
YWHAH	0.01	0	-10000	0	-10000	0	0
VIPR1	-0.38	0.44	-10000	0	-0.86	154	154
NR3C1	0.14	0.18	0.44	61	-10000	0	61
NR4A1	-0.11	0.22	-10000	0	-0.51	83	83
TIF2/SUV420H1	-0.002	0.027	-10000	0	-0.36	2	2
MAPKKK cascade	-0.018	0.16	0.46	10	-0.58	11	21
cortisol/GR alpha (dimer)/Src-1	0.22	0.26	0.53	104	-10000	0	104
PBX1	-0.007	0.091	-10000	0	-0.5	11	11
POU1F1	0.001	0.037	-10000	0	-0.63	1	1
SELE	-0.22	0.4	-10000	0	-1.1	56	56
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.14	0.15	0.37	56	-10000	0	56
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.21	0.24	0.51	98	-10000	0	98
mol:cortisol	0.13	0.19	0.36	100	-0.21	8	108
MMP1	-0.28	0.2	-10000	0	-0.48	107	107

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	-0.002	0.027	-10000	0	-0.36	2	2
Necdin/E2F1	-0.012	0.066	-10000	0	-0.36	12	12
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.031	0.081	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/BEX1	-0.12	0.16	-10000	0	-0.32	130	130
NT-4/5 (dimer)/p75(NTR)	-0.03	0.099	-10000	0	-0.36	29	29
IKBKB	0.01	0	-10000	0	-10000	0	0
AKT1	0	0.087	-10000	0	-10000	0	0
IKBKG	0.01	0	-10000	0	-10000	0	0
BDNF	-0.23	0.26	-10000	0	-0.5	166	166
MGDIs/NGR/p75(NTR)/LINGO1	-0.054	0.12	-10000	0	-0.32	60	60
FURIN	-0.005	0.088	-10000	0	-0.52	10	10
proBDNF (dimer)/p75(NTR)/Sortilin	-0.15	0.16	-10000	0	-0.31	173	173
LINGO1	-0.064	0.18	-10000	0	-0.52	49	49
Sortilin/TRAF6/NRIF	-0.002	0.021	-10000	0	-10000	0	0
proBDNF (dimer)	-0.23	0.26	-10000	0	-0.5	166	166
NTRK1	-0.012	0.1	-10000	0	-0.5	15	15
RTN4R	0.008	0.027	-10000	0	-0.5	1	1
neuron apoptosis	-0.1	0.15	-10000	0	-0.42	22	22
IRAK1	0.008	0.028	-10000	0	-0.52	1	1
SHC1	-0.015	0.1	-10000	0	-0.3	40	40
ARHGDIA	0.01	0	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.018	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.032	0.086	-10000	0	-0.27	42	42
MAGEH1	0.01	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.036	0.096	-10000	0	-0.28	46	46
Mammalian IAPs/DIABLO	-0.005	0.035	-10000	0	-0.27	6	6
proNGF (dimer)	-0.032	0.14	-10000	0	-0.51	28	28
MAGED1	0.008	0.028	-10000	0	-0.52	1	1
APP	0.01	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.015	0.11	-10000	0	-0.5	17	17
ZNF274	0.01	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.028	0.079	-10000	0	-0.25	23	23
NGF	-0.032	0.14	-10000	0	-0.52	28	28
cell cycle arrest	0.009	0.11	-10000	0	-0.29	17	17
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.007	0.065	-10000	0	-10000	0	0
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.024	0.082	-10000	0	-0.3	29	29
NCSTN	0.01	0	-10000	0	-10000	0	0
mol:GTP	-0.035	0.096	-10000	0	-0.3	41	41
PSENEN	0.008	0.028	-10000	0	-0.52	1	1
mol:ceramide	-0.008	0.094	-10000	0	-0.26	42	42
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.014	0.059	-10000	0	-0.39	1	1
p75(NTR)/beta APP	-0.012	0.066	-10000	0	-0.36	12	12
BEX1	-0.14	0.23	-10000	0	-0.51	102	102
mol:GDP	-0.022	0.1	-10000	0	-0.31	40	40
NGF (dimer)	-0.086	0.14	-10000	0	-0.29	104	104
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.048	0.11	-10000	0	-0.28	54	54
PIK3R1	0.01	0	-10000	0	-10000	0	0
RAC1/GTP	-0.029	0.081	-10000	0	-0.26	40	40
MYD88	0.01	0	-10000	0	-10000	0	0
CHUK	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.035	0.097	-10000	0	-0.3	41	41
RHOB	0.01	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.006	0.048	-10000	0	-0.37	6	6
NT3 (dimer)	-0.022	0.12	-10000	0	-0.5	22	22
TP53	-0.094	0.14	-10000	0	-0.47	7	7
PRDM4	-0.008	0.095	-10000	0	-0.27	42	42
BDNF (dimer)	-0.3	0.22	-10000	0	-0.45	189	189
PIK3CA	0.01	0	-10000	0	-10000	0	0
SORT1	0.007	0.039	-10000	0	-0.5	2	2
activation of caspase activity	-0.031	0.081	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.032	0.086	-10000	0	-0.27	42	42
RHOC	0.01	0	-10000	0	-10000	0	0
XIAP	0.01	0	-10000	0	-10000	0	0
MAPK10	-0.09	0.15	-10000	0	-0.41	36	36
DIABLO	0.01	0	-10000	0	-10000	0	0
SMPD2	-0.008	0.095	-10000	0	-0.27	42	42
APH1B	0.008	0.027	-10000	0	-0.5	1	1
APH1A	0.01	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.036	0.098	-10000	0	-0.3	42	42
PSEN1	0.01	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.034	0.11	-10000	0	-0.39	31	31
MAPK8	-0.067	0.13	-10000	0	-0.37	22	22
MAPK9	-0.067	0.13	-10000	0	-0.37	22	22
APAF1	0.01	0	-10000	0	-10000	0	0
NTF3	-0.022	0.12	-10000	0	-0.51	22	22
NTF4	-0.015	0.11	-10000	0	-0.5	17	17
NDN	0.001	0.066	-10000	0	-0.5	6	6
RAC1/GDP	0	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.026	0.071	-10000	0	-10000	0	0
p75 CTF/Sortilin/TRAF6/NRIF	-0.001	0.02	-10000	0	-0.26	2	2
RhoA-B-C/GTP	-0.035	0.096	-10000	0	-0.3	41	41
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.12	0.13	-10000	0	-0.5	7	7
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.13	0.14	-10000	0	-0.27	173	173
PRKACB	0.008	0.028	-10000	0	-0.52	1	1
proBDNF (dimer)/p75 ECD	-0.17	0.18	-10000	0	-0.36	166	166
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.001	0.068	-10000	0	-0.52	6	6
BIRC2	0.01	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.016	0.12	0.18	75	-0.27	13	88
BAD	-0.07	0.13	-10000	0	-0.39	21	21
RIPK2	0.01	0	-10000	0	-10000	0	0
NGFR	-0.008	0.095	-10000	0	-0.51	12	12
CYCS	-0.002	0.092	-10000	0	-0.5	1	1
ADAM17	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.03	0.085	-10000	0	-0.27	40	40
BCL2L11	-0.07	0.13	-10000	0	-0.39	21	21
BDNF (dimer)/p75(NTR)	-0.18	0.19	-10000	0	-0.36	173	173
PI3K	-0.03	0.085	-10000	0	-0.27	40	40
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.032	0.086	-10000	0	-0.27	42	42
NDNL2	0.01	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.041	0.12	-10000	0	-0.36	40	40
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.033	0.09	-10000	0	-0.27	42	42
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.007	0.039	-10000	0	-0.5	2	2
PLG	-0.01	0.078	-10000	0	-0.52	8	8
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.12	0.16	-10000	0	-0.48	25	25
SQSTM1	0.01	0	-10000	0	-10000	0	0
NGFRAP1	0.005	0.047	-10000	0	-0.5	3	3
CASP3	-0.064	0.12	-10000	0	-0.36	21	21
E2F1	0.001	0.069	-10000	0	-0.52	6	6
CASP9	0.01	0	-10000	0	-10000	0	0
IKK complex	-0.028	0.073	-10000	0	-0.4	3	3
NGF (dimer)/TRKA	-0.044	0.12	-10000	0	-0.37	42	42
MMP7	-0.086	0.2	-10000	0	-0.52	64	64
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.029	0.079	-10000	0	-10000	0	0
MMP3	-0.21	0.26	-10000	0	-0.52	146	146
APAF-1/Caspase 9	-0.024	0.062	-10000	0	-0.38	2	2

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.005	0.081	-9999	-0.31	22	22
ADCY5	-0.036	0.12	-9999	-0.31	56	56
ADCY6	0.012	0.034	-9999	-0.3	4	4
ADCY7	0.011	0.037	-9999	-0.3	5	5
ADCY1	0.007	0.053	-9999	-0.31	10	10
ADCY2	-0.019	0.1	-9999	-0.31	37	37
ADCY3	0.013	0.029	-9999	-0.3	3	3
ADCY8	-0.12	0.16	-9999	-0.3	145	145
PRKCE	0.006	0.034	-9999	-0.36	3	3
ADCY9	0.005	0.058	-9999	-0.3	12	12
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.064	0.1	-9999	-0.36	20	20

×

Canonical Wnt signaling pathway

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
HDAC1	0.004	0.019	-10000	0	-10000	0	0
AES	0.003	0.016	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0	-10000	0	-10000	0	0
SMAD4	0.01	0	-10000	0	-10000	0	0
DKK2	-0.075	0.19	-10000	0	-0.5	58	58
TLE1	0.004	0.016	-10000	0	-10000	0	0
MACF1	0.006	0.047	-10000	0	-0.5	3	3
CTNNB1	0.094	0.08	0.24	14	-10000	0	14
WIF1	-0.34	0.24	-10000	0	-0.5	243	243
beta catenin/RanBP3	0.012	0.089	0.4	15	-10000	0	15
KREMEN2	-0.12	0.23	-10000	0	-0.52	85	85
DKK1	-0.12	0.23	-10000	0	-0.52	88	88
beta catenin/beta TrCP1	0.094	0.075	0.24	12	-10000	0	12
FZD1	0.01	0.001	-10000	0	-10000	0	0
AXIN2	-0.031	0.25	-10000	0	-1.3	14	14
AXIN1	0.011	0.001	-10000	0	-10000	0	0
RAN	0.007	0.04	-10000	0	-0.52	2	2
Axin1/APC/GSK3/beta catenin	0.006	0.021	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.075	0.062	0.27	1	-10000	0	1
Axin1/APC/GSK3	0.022	0.063	0.2	34	-10000	0	34
Axin1/APC/GSK3/beta catenin/Macf1	0.067	0.045	-10000	0	-10000	0	0
HNF1A	-0.092	0.21	-10000	0	-0.53	64	64
CTBP1	0.004	0.017	-10000	0	-10000	0	0
MYC	0.004	0.12	-10000	0	-1.4	2	2
RANBP3	0.01	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.12	0.18	-10000	0	-0.36	120	120
NKD1	-0.059	0.18	-10000	0	-0.51	47	47
TCF4	0.001	0.042	-10000	0	-0.51	2	2
TCF3	0.004	0.017	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.005	0.037	-10000	0	-0.27	7	7
Ran/GTP	-0.001	0.029	-10000	0	-0.38	2	2
CtBP/CBP/TCF/TLE1/AES	0.003	0.11	0.45	17	-10000	0	17
LEF1	0.001	0.043	-10000	0	-0.53	2	2
DVL1	0.073	0.055	0.19	1	-0.28	1	2
CSNK2A1	0.01	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.078	0.069	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.15	0.19	-10000	0	-0.36	146	146
LRP6	0.01	0.001	-10000	0	-10000	0	0
CSNK1A1	0.004	0.019	-10000	0	-10000	0	0
NLK	0.01	0.002	-10000	0	-10000	0	0
CCND1	0.001	0.14	-10000	0	-1.4	3	3
WNT1	-0.001	0.074	-10000	0	-0.52	7	7
GSK3A	0.011	0.001	-10000	0	-10000	0	0
GSK3B	0.009	0.002	-10000	0	-10000	0	0
FRAT1	0.009	0.002	-10000	0	-10000	0	0
PPP2R5D	0.076	0.091	0.3	47	-10000	0	47
APC	0.024	0.04	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.15	0.1	0.22	238	-10000	0	238
CREBBP	0.004	0.017	-10000	0	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.002	0.023	-9999	-0.3	2	2
ARNO/beta Arrestin1-2	-0.094	0.12	-9999	-0.44	3	3
EGFR	-0.005	0.087	-9999	-0.52	10	10
EPHA2	0.002	0.061	-9999	-0.5	5	5
USP6	0.01	0	-9999	-10000	0	0
IQSEC1	0.008	0.027	-9999	-0.5	1	1
EGFR/EGFR/EGF/EGF	-0.08	0.16	-9999	-0.38	75	75
ARRB2	-0.006	0.055	-9999	-0.19	28	28
mol:GTP	0.011	0.023	-9999	-0.13	2	2
ARRB1	0.004	0.054	-9999	-0.5	4	4
FBXO8	0.01	0	-9999	-10000	0	0
TSHR	-0.047	0.16	-9999	-0.52	37	37
EGF	-0.091	0.21	-9999	-0.52	67	67
somatostatin receptor activity	0	0	-9999	-0.001	56	56
ARAP2	-0.012	0.1	-9999	-0.5	15	15
mol:GDP	-0.084	0.12	-9999	-0.26	81	81
mol:PI-3-4-5-P3	0	0	-9999	-0.001	39	39
ITGA2B	-0.043	0.16	-9999	-0.5	36	36
ARF6	0.01	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.004	0.034	-9999	-10000	0	0
ADAP1	0.008	0.027	-9999	-0.5	1	1
KIF13B	0.008	0.027	-9999	-0.5	1	1
HGF/MET	-0.042	0.12	-9999	-0.39	38	38
PXN	0.01	0	-9999	-10000	0	0
ARF6/GTP	-0.081	0.11	-9999	-0.26	56	56
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.068	0.13	-9999	-0.32	75	75
ADRB2	-0.19	0.25	-9999	-0.5	136	136
receptor agonist activity	0	0	-9999	0	76	76
actin filament binding	0	0	-9999	-0.001	62	62
SRC	0.01	0	-9999	-10000	0	0
ITGB3	-0.025	0.13	-9999	-0.52	23	23
GNAQ	0.008	0.027	-9999	-0.5	1	1
EFA6/PI-4-5-P2	0	0	-9999	-0.001	56	56
ARF6/GDP	-0.011	0.079	-9999	-0.38	7	7
ARF6/GDP/GULP/ACAP1	-0.077	0.096	-9999	-0.29	30	30
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.044	0.1	-9999	-0.28	22	22
ACAP1	0.007	0.039	-9999	-0.5	2	2
ACAP2	0.008	0.028	-9999	-0.52	1	1
LHCGR/beta Arrestin2	-0.022	0.075	-9999	-0.28	28	28
EFNA1	0.008	0.027	-9999	-0.5	1	1
HGF	-0.017	0.11	-9999	-0.51	18	18
CYTH3	0.007	0.029	-9999	-0.38	2	2
CYTH2	0.006	0.002	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	46	46
endosomal lumen acidification	0	0	-9999	0	21	21
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	0.008	0.027	-9999	-0.5	1	1
GNAQ/ARNO	0.006	0.015	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	13	13
MET	-0.024	0.13	-9999	-0.51	23	23
GNA14	-0.008	0.093	-9999	-0.5	12	12
GNA15	0.01	0	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	56	56
GNA11	0.008	0.027	-9999	-0.5	1	1
LHCGR	-0.037	0.14	-9999	-0.52	28	28
AGTR1	-0.14	0.24	-9999	-0.5	105	105
desensitization of G-protein coupled receptor protein signaling pathway	-0.022	0.075	-9999	-0.28	28	28
IPCEF1/ARNO	-0.051	0.1	-9999	-0.48	2	2
alphaIIb/beta3 Integrin	-0.06	0.14	-9999	-0.37	58	58

×

Integrins in angiogenesis

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	-0.007	0.05	-9999	-0.36	7	7
alphaV beta3 Integrin	-0.055	0.12	-9999	-0.32	61	61
PTK2	-0.058	0.15	-9999	-0.45	25	25
IGF1R	0.008	0.027	-9999	-0.5	1	1
PI4KB	0.01	0	-9999	-10000	0	0
MFGE8	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
CDKN1B	-0.099	0.19	-9999	-0.5	59	59
VEGFA	0.01	0	-9999	-10000	0	0
ILK	-0.099	0.19	-9999	-0.5	59	59
ROCK1	0.01	0	-9999	-10000	0	0
AKT1	-0.091	0.18	-9999	-0.47	58	58
PTK2B	0.007	0.084	-9999	-0.49	2	2
alphaV/beta3 Integrin/JAM-A	-0.089	0.15	-9999	-0.53	20	20
CBL	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.038	0.1	-9999	-0.31	44	44
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.005	0.042	-9999	-0.53	1	1
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.016	0.097	-9999	-0.36	7	7
alphaV/beta3 Integrin/Syndecan-1	-0.02	0.075	-9999	-0.31	23	23
PI4KA	0.01	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.046	0.11	-9999	-0.53	9	9
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.25	0.15	-9999	-0.33	269	269
RPS6KB1	-0.006	0.12	-9999	-0.49	9	9
TLN1	0.008	0.027	-9999	-0.5	1	1
MAPK3	-0.087	0.18	-9999	-0.53	44	44
GPR124	0.005	0.047	-9999	-0.5	3	3
MAPK1	-0.087	0.18	-9999	-0.53	44	44
PXN	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.12	0.15	-9999	-0.31	132	132
cell adhesion	-0.029	0.076	-9999	-0.28	4	4
ANGPTL3	-0.026	0.12	-9999	-0.52	21	21
VEGFR2 homodimer/VEGFA homodimer/Src	-0.006	0.041	-9999	-0.29	7	7
IGF-1R heterotetramer	0.008	0.027	-9999	-0.5	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.001	0.066	-9999	-0.5	6	6
ITGB3	-0.025	0.13	-9999	-0.52	23	23
IGF1	0.002	0.061	-9999	-0.51	5	5
RAC1	0.01	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.022	0.085	-9999	-0.33	24	24
apoptosis	0.01	0	-9999	-10000	0	0
CD47	0.008	0.027	-9999	-0.5	1	1
alphaV/beta3 Integrin/CD47	-0.021	0.077	-9999	-0.3	24	24
VCL	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.041	0.11	-9999	-0.33	44	44
CSF1	0.005	0.047	-9999	-0.5	3	3
PIK3C2A	-0.099	0.19	-9999	-0.5	59	59
PI4 Kinase/Pyk2	-0.076	0.13	-9999	-0.46	23	23
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.023	0.077	-9999	-0.28	29	29
FAK1/Vinculin	-0.041	0.12	-9999	-0.36	24	24
alphaV beta3/Integrin/ppsTEM5	-0.022	0.085	-9999	-0.33	24	24
RHOA	0.01	0	-9999	-10000	0	0
VTN	-0.082	0.2	-9999	-0.5	63	63
BCAR1	0.008	0.027	-9999	-0.5	1	1
FGF2	-0.051	0.17	-9999	-0.5	42	42
F11R	-0.027	0.12	-9999	-0.36	43	43
alphaV/beta3 Integrin/Lactadherin	-0.02	0.075	-9999	-0.31	23	23
alphaV/beta3 Integrin/TGFBR2	-0.025	0.083	-9999	-0.3	29	29
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.003	0.028	-9999	-0.26	4	4
HSP90AA1	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.019	0.072	-9999	-0.29	23	23
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.004	0.054	-9999	-0.5	4	4
alphaV/beta3 Integrin/Pyk2	-0.022	0.075	-9999	-0.49	2	2
SDC1	0.01	0	-9999	-10000	0	0
VAV3	0.025	0.045	-9999	-0.49	1	1
PTPN11	0.01	0	-9999	-10000	0	0
IRS1	0.008	0.027	-9999	-0.5	1	1
FAK1/Paxillin	-0.041	0.12	-9999	-0.36	24	24
cell migration	-0.031	0.12	-9999	-0.37	12	12
ITGAV	0.01	0	-9999	-10000	0	0
PI3K	-0.078	0.14	-9999	-0.48	20	20
SPP1	-0.39	0.23	-9999	-0.52	264	264
KDR	0	0.072	-9999	-0.5	7	7
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.01	0	-9999	-10000	0	0
COL4A3	-0.16	0.24	-9999	-0.5	114	114
angiogenesis	-0.064	0.21	-9999	-0.53	45	45
Rac1/GTP	-0.005	0.037	-9999	-0.45	1	1
EDIL3	-0.027	0.13	-9999	-0.5	25	25
cell proliferation	-0.025	0.083	-9999	-0.3	29	29

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0	-9999	-10000	0	0
CCL5	0.004	0.054	-9999	-0.5	4	4
SDCBP	0.01	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.12	0.11	-9999	-0.35	18	18
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.11	0.1	-9999	-0.34	21	21
Syndecan-1/Syntenin	-0.1	0.1	-9999	-0.33	18	18
MAPK3	-0.085	0.095	-9999	-0.5	2	2
HGF/MET	-0.042	0.12	-9999	-0.39	38	38
TGFB1/TGF beta receptor Type II	0.01	0	-9999	-10000	0	0
BSG	0.01	0	-9999	-10000	0	0
keratinocyte migration	-0.1	0.1	-9999	-0.34	21	21
Syndecan-1/RANTES	-0.11	0.1	-9999	-0.34	21	21
Syndecan-1/CD147	-0.1	0.086	-9999	-0.32	19	19
Syndecan-1/Syntenin/PIP2	-0.11	0.087	-9999	-0.32	18	18
LAMA5	0.005	0.047	-9999	-0.5	3	3
positive regulation of cell-cell adhesion	-0.11	0.085	-9999	-0.31	18	18
MMP7	-0.086	0.2	-9999	-0.52	64	64
HGF	-0.017	0.11	-9999	-0.51	18	18
Syndecan-1/CASK	-0.11	0.1	-9999	-0.34	18	18
Syndecan-1/HGF/MET	-0.13	0.12	-9999	-0.38	45	45
regulation of cell adhesion	-0.077	0.093	-9999	-0.48	2	2
HPSE	0.007	0.04	-9999	-0.52	2	2
positive regulation of cell migration	-0.12	0.11	-9999	-0.35	18	18
SDC1	-0.12	0.11	-9999	-0.36	18	18
Syndecan-1/Collagen	-0.12	0.11	-9999	-0.35	18	18
PPIB	0.008	0.028	-9999	-0.52	1	1
MET	-0.024	0.13	-9999	-0.51	23	23
PRKACA	0.01	0	-9999	-10000	0	0
MMP9	-0.081	0.2	-9999	-0.52	60	60
MAPK1	-0.085	0.095	-9999	-0.5	2	2
homophilic cell adhesion	-0.12	0.11	-9999	-0.35	18	18
MMP1	-0.36	0.24	-9999	-0.52	246	246

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.013	0.071	-10000	0	-0.54	5	5
HDAC1	0.001	0.006	-10000	0	-10000	0	0
AES	0.009	0.002	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
DTX1	0.005	0.049	-10000	0	-0.52	3	3
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	0.009	0.002	-10000	0	-10000	0	0
AP1	-0.037	0.13	-10000	0	-0.29	64	64
NCSTN	0.01	0	-10000	0	-10000	0	0
ADAM10	0.01	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.013	0.054	-10000	0	-10000	0	0
NICD/RBPSUH	-0.008	0.064	-10000	0	-0.54	5	5
WIF1	-0.34	0.24	-10000	0	-0.5	243	243
NOTCH1	-0.008	0.068	-10000	0	-0.57	5	5
PSENEN	0.008	0.028	-10000	0	-0.52	1	1
KREMEN2	-0.12	0.23	-10000	0	-0.52	85	85
DKK1	-0.12	0.23	-10000	0	-0.52	88	88
beta catenin/beta TrCP1	0.02	0.055	-10000	0	-10000	0	0
APH1B	0.008	0.027	-10000	0	-0.5	1	1
APH1A	0.01	0	-10000	0	-10000	0	0
AXIN1	-0.007	0.029	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	-0.023	0.058	0.28	1	-10000	0	1
PSEN1	0.01	0	-10000	0	-10000	0	0
FOS	-0.03	0.14	-10000	0	-0.5	27	27
JUN	0.007	0.039	-10000	0	-0.5	2	2
MAP3K7	0.008	0.002	-10000	0	-10000	0	0
CTNNB1	0.016	0.059	-10000	0	-10000	0	0
MAPK3	0.01	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.12	0.18	-10000	0	-0.36	120	120
HNF1A	-0.088	0.2	-10000	0	-0.52	64	64
CTBP1	0.009	0.002	-10000	0	-10000	0	0
MYC	0.014	0.1	-10000	0	-1.3	2	2
NKD1	-0.059	0.18	-10000	0	-0.51	47	47
FZD1	0.01	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.01	0.067	-10000	0	-0.54	5	5
apoptosis	-0.037	0.13	-10000	0	-0.29	64	64
Delta 1/NOTCHprecursor	-0.013	0.071	-10000	0	-0.54	5	5
DLL1	0	0.072	-10000	0	-0.5	7	7
PPARD	0.021	0.013	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.019	-10000	0	-10000	0	0
APC	-0.007	0.029	-10000	0	-10000	0	0
DVL1	-0.032	0.037	-10000	0	-0.43	2	2
CSNK2A1	0.01	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.15	0.19	-10000	0	-0.36	146	146
LRP6	0.01	0	-10000	0	-10000	0	0
CSNK1A1	0.01	0.001	-10000	0	-10000	0	0
NLK	0.01	0.005	-10000	0	-10000	0	0
CCND1	0.01	0.12	-10000	0	-1.3	3	3
WNT1	-0.002	0.074	-10000	0	-0.52	7	7
Axin1/APC/beta catenin	0.012	0.044	-10000	0	-0.28	1	1
DKK2	-0.075	0.19	-10000	0	-0.5	58	58
NOTCH1 precursor/DVL1	-0.019	0.065	-10000	0	-0.49	6	6
GSK3B	0.009	0	-10000	0	-10000	0	0
FRAT1	0.009	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.01	0.068	-10000	0	-0.54	5	5
PPP2R5D	0.018	0.089	0.24	47	-0.2	1	48
MAPK1	0.01	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.18	0.12	-10000	0	-0.26	246	246
RBPJ	0.01	0	-10000	0	-10000	0	0
CREBBP	0.013	0.001	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.025	0.071	-9999	-0.3	2	2
BIRC5	-0.31	0.26	-9999	-0.52	213	213
NFKBIA	-0.014	0.072	-9999	-10000	0	0
CPEB1	-0.064	0.18	-9999	-0.5	50	50
AKT1	-0.014	0.072	-9999	-10000	0	0
NDEL1	0.01	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.022	0.064	-9999	-0.42	1	1
NDEL1/TACC3	-0.016	0.059	-9999	-0.39	1	1
GADD45A	0.007	0.039	-9999	-0.51	2	2
GSK3B	0.011	0.004	-9999	-10000	0	0
PAK1/Aurora A	-0.023	0.068	-9999	-10000	0	0
MDM2	0.007	0.04	-9999	-0.52	2	2
JUB	0.008	0.027	-9999	-0.5	1	1
TPX2	-0.21	0.2	-9999	-0.38	203	203
TP53	-0.01	0.045	-9999	-0.19	1	1
DLG7	-0.022	0.072	-9999	-10000	0	0
AURKAIP1	0.01	0	-9999	-10000	0	0
ARHGEF7	0.01	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.018	0.063	-9999	-0.41	1	1
G2/M transition of mitotic cell cycle	-0.022	0.063	-9999	-0.42	1	1
AURKA	-0.025	0.088	-9999	-0.2	1	1
AURKB	-0.062	0.057	-9999	-0.14	76	76
CDC25B	-0.016	0.056	-9999	-10000	0	0
G2/M transition checkpoint	-0.022	0.061	-9999	-0.26	1	1
mRNA polyadenylation	-0.061	0.12	-9999	-0.31	50	50
Aurora A/CPEB	-0.061	0.12	-9999	-0.31	50	50
Aurora A/TACC1/TRAP/chTOG	-0.022	0.077	-9999	-0.37	5	5
BRCA1	0.008	0.028	-9999	-0.52	1	1
centrosome duplication	-0.023	0.068	-9999	-10000	0	0
regulation of centrosome cycle	-0.016	0.058	-9999	-0.38	1	1
spindle assembly	-0.022	0.076	-9999	-0.37	5	5
TDRD7	0.01	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.17	0.15	-9999	-0.3	190	190
CENPA	-0.058	0.057	-9999	-0.15	76	76
Aurora A/PP2A	-0.023	0.068	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.001	0.054	-9999	-10000	0	0
negative regulation of DNA binding	-0.002	0.048	-9999	-0.19	1	1
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.022	0.062	-9999	-0.27	1	1
mitotic prometaphase	0.016	0.015	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.025	0.088	-9999	-0.2	1	1
TACC1	-0.011	0.1	-9999	-0.5	14	14
TACC3	0.008	0.028	-9999	-0.52	1	1
Aurora A/Antizyme1	-0.017	0.059	-9999	-10000	0	0
Aurora A/RasGAP	-0.023	0.068	-9999	-10000	0	0
OAZ1	0.01	0	-9999	-10000	0	0
RAN	0.007	0.04	-9999	-0.52	2	2
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.011	0.004	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.21	0.2	-9999	-0.37	203	203
PPP2R5D	0.01	0	-9999	-10000	0	0
Aurora A/TPX2	-0.18	0.18	-9999	-0.33	203	203
PAK1	0.01	0	-9999	-10000	0	0
CKAP5	0.01	0	-9999	-10000	0	0

×

Glypican 1 network

Figure S31. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S31. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.039	0.11	-10000	0	-0.31	44	44
fibroblast growth factor receptor signaling pathway	-0.039	0.11	-10000	0	-0.31	44	44
LAMA1	-0.023	0.13	-10000	0	-0.52	22	22
PRNP	0.008	0.027	-10000	0	-0.5	1	1
GPC1/SLIT2	-0.079	0.15	-10000	0	-0.36	78	78
SMAD2	0.019	0.045	-10000	0	-0.27	1	1
GPC1/PrPc/Cu2+	-0.003	0.028	-10000	0	-0.3	3	3
GPC1/Laminin alpha1	-0.025	0.095	-10000	0	-0.38	23	23
TDGF1	-0.022	0.12	-10000	0	-0.51	21	21
CRIPTO/GPC1	-0.024	0.09	-10000	0	-0.36	23	23
APP/GPC1	-0.002	0.027	-10000	0	-0.36	2	2
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0	0.079	-10000	0	-0.3	23	23
FLT1	0.01	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.008	0.047	-10000	0	-0.3	9	9
SERPINC1	-0.003	0.074	-10000	0	-0.52	7	7
FYN	0	0.079	-10000	0	-0.3	23	23
FGR	-0.028	0.12	-10000	0	-0.33	50	50
positive regulation of MAPKKK cascade	-0.015	0.12	-10000	0	-0.37	25	25
SLIT2	-0.1	0.21	-10000	0	-0.5	76	76
GPC1/NRG	-0.068	0.14	-10000	0	-0.36	67	67
NRG1	-0.085	0.2	-10000	0	-0.5	65	65
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.002	0.022	-10000	0	-0.29	2	2
LYN	0	0.079	-10000	0	-0.3	23	23
mol:Spermine	0.007	0.028	-10000	0	-0.36	2	2
cell growth	-0.039	0.11	-10000	0	-0.31	44	44
BMP signaling pathway	-0.007	0.038	0.5	2	-10000	0	2
SRC	0	0.079	-10000	0	-0.3	23	23
TGFBR1	0.008	0.028	-10000	0	-0.52	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.069	0.19	-10000	0	-0.51	54	54
GPC1	0.007	0.039	-10000	0	-0.5	2	2
TGFBR1 (dimer)	0.008	0.028	-10000	0	-0.52	1	1
VEGFA	0.01	0	-10000	0	-10000	0	0
BLK	-0.039	0.13	-10000	0	-0.31	63	63
HCK	-0.012	0.1	-10000	0	-0.32	35	35
FGF2	-0.051	0.17	-10000	0	-0.5	42	42
FGFR1	0.005	0.048	-10000	0	-0.51	3	3
VEGFR1 homodimer	0.01	0	-10000	0	-10000	0	0
TGFBR2	0.001	0.066	-10000	0	-0.5	6	6
cell death	-0.002	0.027	-10000	0	-0.36	2	2
ATIII/GPC1	-0.009	0.058	-10000	0	-0.37	9	9
PLA2G2A/GPC1	-0.057	0.13	-10000	0	-0.36	56	56
LCK	-0.001	0.083	-10000	0	-0.3	25	25
neuron differentiation	-0.067	0.14	-10000	0	-0.36	67	67
PrPc/Cu2+	-0.001	0.019	-10000	0	-0.36	1	1
APP	0.01	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.001	0.066	-10000	0	-0.5	6	6

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.026	0.025	-9999	-10000	0	0
VDR	0.007	0.039	-9999	-0.51	2	2
FAM120B	0.01	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.089	0.14	-9999	-0.46	8	8
RXRs/LXRs/DNA/Oxysterols	-0.072	0.14	-9999	-0.47	16	16
MED1	0.01	0	-9999	-10000	0	0
mol:9cRA	0.003	0.01	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.003	0.079	-9999	-0.46	1	1
RXRs/NUR77	-0.17	0.18	-9999	-0.48	45	45
RXRs/PPAR	-0.13	0.16	-9999	-0.44	36	36
NCOR2	0.01	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.028	-9999	-0.37	2	2
RARs/VDR/DNA/Vit D3	-0.003	0.026	-9999	-0.26	1	1
RARA	0.01	0	-9999	-10000	0	0
NCOA1	0.01	0	-9999	-10000	0	0
VDR/VDR/DNA	0.007	0.039	-9999	-0.51	2	2
RARs/RARs/DNA/9cRA	-0.001	0.019	-9999	-0.26	2	2
RARG	0.01	0	-9999	-10000	0	0
RPS6KB1	0.042	0.04	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.003	0.079	-9999	-0.46	1	1
THRA	0.01	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.002	0.028	-9999	-0.37	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.15	-9999	-0.26	177	177
NR1H4	-0.029	0.13	-9999	-0.52	23	23
RXRs/LXRs/DNA	-0.092	0.14	-9999	-0.39	8	8
NR1H2	0.013	0.008	-9999	-10000	0	0
NR1H3	0.013	0.008	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.11	0.14	-9999	-0.33	10	10
NR4A1	-0.096	0.21	-9999	-0.5	73	73
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.094	0.12	-9999	-0.31	17	17
RXRG	-0.25	0.26	-9999	-0.5	177	177
RXR alpha/CCPG	0.009	0.009	-9999	-10000	0	0
RXRA	0.013	0.008	-9999	-10000	0	0
RXRB	0.013	0.008	-9999	-10000	0	0
THRB	-0.041	0.15	-9999	-0.5	35	35
PPARG	-0.06	0.18	-9999	-0.5	48	48
PPARD	0.01	0	-9999	-10000	0	0
TNF	-0.087	0.23	-9999	-1	16	16
mol:Oxysterols	0.003	0.009	-9999	-10000	0	0
cholesterol transport	-0.071	0.14	-9999	-0.47	16	16
PPARA	0.01	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.007	0.039	-9999	-0.5	2	2
RXRs/NUR77/BCL2	-0.16	0.15	-9999	-0.27	214	214
SREBF1	-0.059	0.13	-9999	-0.53	8	8
RXRs/RXRs/DNA/9cRA	-0.12	0.15	-9999	-0.26	177	177
ABCA1	-0.059	0.13	-9999	-0.53	8	8
RARs/THRs	-0.025	0.075	-9999	-0.49	1	1
RXRs/FXR	-0.13	0.16	-9999	-0.43	19	19
BCL2	0.007	0.04	-9999	-0.52	2	2

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.005	0.047	-10000	0	-0.5	3	3
EPHB2	-0.057	0.18	-10000	0	-0.52	45	45
EFNB1	0.013	0.045	-10000	0	-0.37	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.062	0.12	-10000	0	-0.49	11	11
Ephrin B2/EPHB1-2	-0.067	0.13	-10000	0	-0.3	80	80
neuron projection morphogenesis	-0.059	0.12	-10000	0	-0.47	11	11
Ephrin B1/EPHB1-2/Tiam1	-0.064	0.13	-10000	0	-0.53	11	11
DNM1	0.004	0.056	-10000	0	-0.52	4	4
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.045	0.18	-10000	0	-0.57	37	37
YES1	-0.082	0.24	-10000	0	-0.8	37	37
Ephrin B1/EPHB1-2/NCK2	-0.06	0.13	-10000	0	-0.51	10	10
PI3K	-0.046	0.18	-10000	0	-0.57	37	37
mol:GDP	-0.066	0.13	-10000	0	-0.52	11	11
ITGA2B	-0.043	0.16	-10000	0	-0.5	36	36
endothelial cell proliferation	-0.003	0.027	-10000	0	-0.3	3	3
FYN	-0.082	0.24	-10000	0	-0.8	37	37
MAP3K7	-0.063	0.19	-10000	0	-0.61	37	37
FGR	-0.096	0.25	-10000	0	-0.81	37	37
TIAM1	0.001	0.066	-10000	0	-0.5	6	6
PIK3R1	0.01	0	-10000	0	-10000	0	0
RGS3	0.01	0	-10000	0	-10000	0	0
cell adhesion	-0.072	0.2	-10000	0	-0.56	37	37
LYN	-0.082	0.24	-10000	0	-0.8	37	37
Ephrin B1/EPHB1-2/Src Family Kinases	-0.077	0.23	-10000	0	-0.74	37	37
Ephrin B1/EPHB1-2	-0.072	0.2	-10000	0	-0.66	37	37
SRC	-0.082	0.24	-10000	0	-0.79	37	37
ITGB3	-0.025	0.13	-10000	0	-0.52	23	23
EPHB1	-0.051	0.17	-10000	0	-0.52	40	40
EPHB4	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.003	0.028	-10000	0	-0.3	3	3
alphaIIb/beta3 Integrin	-0.06	0.14	-10000	0	-0.37	58	58
BLK	-0.086	0.24	-10000	0	-0.79	37	37
HCK	-0.088	0.25	-10000	0	-0.81	37	37
regulation of stress fiber formation	0.062	0.12	0.5	10	-10000	0	10
MAPK8	-0.037	0.17	-10000	0	-0.54	37	37
Ephrin B1/EPHB1-2/RGS3	-0.06	0.13	-10000	0	-0.51	10	10
endothelial cell migration	-0.053	0.16	-10000	0	-0.51	38	38
NCK2	0.01	0	-10000	0	-10000	0	0
PTPN13	-0.059	0.19	-10000	0	-0.62	37	37
regulation of focal adhesion formation	0.062	0.12	0.5	10	-10000	0	10
chemotaxis	0.062	0.12	0.5	10	-10000	0	10
PIK3CA	0.01	0	-10000	0	-10000	0	0
Rac1/GTP	-0.06	0.12	-10000	0	-0.48	11	11
angiogenesis	-0.071	0.2	-10000	0	-0.66	37	37
LCK	-0.083	0.24	-10000	0	-0.79	37	37

×

Effects of Botulinum toxin

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.077	0.16	-9999	-0.38	78	78
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.043	0.12	-9999	-0.36	42	42
STXBP1	0.005	0.047	-9999	-0.5	3	3
ACh/CHRNA1	-0.034	0.1	-9999	-0.35	31	31
RAB3GAP2/RIMS1/UNC13B	-0.036	0.097	-9999	-0.3	42	42
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.053	0.17	-9999	-0.51	42	42
mol:ACh	-0.014	0.04	-9999	-0.08	88	88
RAB3GAP2	0.01	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.077	0.11	-9999	-0.37	17	17
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.034	0.1	-9999	-0.35	31	31
UNC13B	0.01	0	-9999	-10000	0	0
CHRNA1	-0.037	0.15	-9999	-0.52	31	31
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.034	0.11	-9999	-0.37	32	32
SNAP25	-0.003	0.043	-9999	-0.19	17	17
VAMP2	0.005	0	-9999	-10000	0	0
SYT1	-0.038	0.15	-9999	-0.52	32	32
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.061	0.14	-9999	-0.31	81	81
STX1A/SNAP25 fragment 1/VAMP2	-0.077	0.11	-9999	-0.37	17	17

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.01	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.039	0.076	-10000	0	-0.27	14	14
NT3 (dimer)/TRKC	-0.088	0.17	-10000	0	-0.4	78	78
NT3 (dimer)/TRKB	-0.13	0.17	-10000	0	-0.33	138	138
SHC/Grb2/SOS1/GAB1/PI3K	0.029	0.013	-10000	0	-0.22	1	1
RAPGEF1	0.01	0	-10000	0	-10000	0	0
BDNF	-0.23	0.26	-10000	0	-0.5	166	166
PIK3CA	0.01	0	-10000	0	-10000	0	0
DYNLT1	0.01	0	-10000	0	-10000	0	0
NTRK1	-0.012	0.1	-10000	0	-0.5	15	15
NTRK2	-0.17	0.24	-10000	0	-0.5	121	121
NTRK3	-0.088	0.2	-10000	0	-0.5	67	67
NT-4/5 (dimer)/TRKB	-0.12	0.17	-10000	0	-0.33	133	133
neuron apoptosis	0.2	0.2	0.49	89	-10000	0	89
SHC 2-3/Grb2	-0.21	0.22	-10000	0	-0.54	89	89
SHC1	0.01	0	-10000	0	-10000	0	0
SHC2	-0.13	0.14	-10000	0	-0.44	40	40
SHC3	-0.22	0.27	-10000	0	-0.64	85	85
STAT3 (dimer)	0.013	0.031	-10000	0	-0.33	3	3
NT3 (dimer)/TRKA	-0.041	0.11	-10000	0	-0.32	45	45
RIN/GDP	-0.022	0.077	-10000	0	-0.23	10	10
GIPC1	0.01	0	-10000	0	-10000	0	0
KRAS	0.01	0	-10000	0	-10000	0	0
DNAJA3	-0.028	0.072	-10000	0	-0.33	7	7
RIN/GTP	-0.002	0.028	-10000	0	-0.38	2	2
CCND1	0.018	0.069	-10000	0	-0.73	3	3
MAGED1	0.008	0.028	-10000	0	-0.52	1	1
PTPN11	0.01	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.015	0.11	-10000	0	-0.5	17	17
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.052	0.13	-10000	0	-0.34	54	54
TRKA/NEDD4-2	-0.015	0.072	-10000	0	-0.36	15	15
ELMO1	0.004	0.055	-10000	0	-0.51	4	4
RhoG/GTP/ELMO1/DOCK1	-0.003	0.032	-10000	0	-0.3	4	4
NGF	-0.032	0.14	-10000	0	-0.52	28	28
HRAS	0.01	0	-10000	0	-10000	0	0
DOCK1	0.01	0	-10000	0	-10000	0	0
GAB2	0.004	0.054	-10000	0	-0.5	4	4
RIT2	-0.002	0.039	-10000	0	-0.52	2	2
RIT1	0.01	0	-10000	0	-10000	0	0
FRS2	0.007	0.04	-10000	0	-0.52	2	2
DNM1	0.004	0.056	-10000	0	-0.52	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.01	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.03	0.078	-10000	0	-0.34	11	11
mol:GDP	-0.032	0.11	-10000	0	-0.3	18	18
NGF (dimer)	-0.032	0.14	-10000	0	-0.51	28	28
RhoG/GDP	-0.004	0.039	-10000	0	-0.37	4	4
RIT1/GDP	-0.017	0.076	-10000	0	-0.22	7	7
TIAM1	0.001	0.066	-10000	0	-0.5	6	6
PIK3R1	0.01	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.24	0.2	-10000	0	-0.36	229	229
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.002	0.023	-10000	0	-0.31	2	2
SHC/GRB2/SOS1/GAB1	-0.001	0.014	-10000	0	-0.26	1	1
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.022	0.12	-10000	0	-0.5	22	22
RAP1/GDP	-0.031	0.053	-10000	0	-0.24	1	1
KIDINS220/CRKL	0.01	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.23	0.26	-10000	0	-0.5	166	166
ubiquitin-dependent protein catabolic process	-0.036	0.1	-10000	0	-0.3	42	42
Schwann cell development	-0.045	0.034	-10000	0	-10000	0	0
EHD4	0.01	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.002	0.02	-10000	0	-0.27	2	2
FRS2 family/SHP2/CRK family/C3G/GAB2	0.029	0.025	-10000	0	-10000	0	0
RAP1B	0.01	0	-10000	0	-10000	0	0
RAP1A	0.01	0	-10000	0	-10000	0	0
CDC42/GTP	-0.23	0.21	-10000	0	-0.51	107	107
ABL1	0.01	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.085	0.072	-10000	0	-10000	0	0
STAT3	0.013	0.031	-10000	0	-0.32	3	3
axon guidance	-0.22	0.2	-10000	0	-0.48	107	107
MAPK3	-0.024	0.12	-10000	0	-0.53	8	8
MAPK1	-0.024	0.12	-10000	0	-0.36	23	23
CDC42/GDP	-0.017	0.076	-10000	0	-0.22	9	9
NTF3	-0.022	0.12	-10000	0	-0.51	22	22
NTF4	-0.015	0.11	-10000	0	-0.5	17	17
NGF (dimer)/TRKA/FAIM	-0.036	0.1	-10000	0	-0.31	42	42
PI3K	0	0	-10000	0	-10000	0	0
FRS3	0.01	0	-10000	0	-10000	0	0
FAIM	0.01	0	-10000	0	-10000	0	0
GAB1	0.008	0.027	-10000	0	-0.5	1	1
RASGRF1	-0.13	0.15	-10000	0	-0.42	35	35
SOS1	0.01	0	-10000	0	-10000	0	0
MCF2L	-0.058	0.16	-10000	0	-0.34	79	79
RGS19	0.01	0	-10000	0	-10000	0	0
CDC42	0.01	0	-10000	0	-10000	0	0
RAS family/GTP	-0.01	0.064	-10000	0	-10000	0	0
Rac1/GDP	-0.017	0.076	-10000	0	-0.22	9	9
NGF (dimer)/TRKA/GRIT	-0.037	0.1	-10000	0	-0.31	42	42
neuron projection morphogenesis	-0.002	0.082	-10000	0	-0.45	2	2
NGF (dimer)/TRKA/NEDD4-2	-0.036	0.1	-10000	0	-0.31	42	42
MAP2K1	0.031	0.014	-10000	0	-10000	0	0
NGFR	-0.008	0.095	-10000	0	-0.51	12	12
NGF (dimer)/TRKA/GIPC/GAIP	0.002	0.074	-10000	0	-0.37	1	1
RAS family/GTP/PI3K	0.025	0	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.019	-10000	0	-10000	0	0
NRAS	0.01	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.007	0.039	-10000	0	-0.5	2	2
MAPKKK cascade	-0.088	0.17	-10000	0	-0.66	26	26
RASA1	0.01	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.015	0.072	-10000	0	-0.36	15	15
SQSTM1	0.01	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.21	0.18	-10000	0	-0.51	61	61
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.031	0.085	-10000	0	-0.5	2	2
MATK	-0.018	0.12	-10000	0	-0.5	19	19
NEDD4L	0.01	0	-10000	0	-10000	0	0
RAS family/GDP	-0.026	0.049	-10000	0	-0.23	1	1
NGF (dimer)/TRKA	-0.03	0.078	-10000	0	-0.25	30	30
Rac1/GTP	-0.087	0.099	-10000	0	-0.3	36	36
FRS2 family/SHP2/CRK family	-0.001	0.019	-10000	0	-10000	0	0

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.003	0.055	-10000	0	-0.51	4	4
GNB1/GNG2	-0.032	0.067	-10000	0	-0.18	53	53
AKT1	0.009	0.095	-10000	0	-0.21	24	24
EGF	-0.091	0.21	-10000	0	-0.52	67	67
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.022	0.078	-10000	0	-0.43	6	6
mol:Ca2+	-0.007	0.14	-10000	0	-0.3	57	57
LYN	-0.003	0.04	-10000	0	-0.37	2	2
RhoA/GTP	-0.021	0.045	-10000	0	-0.14	8	8
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.008	0.15	-10000	0	-0.34	55	55
GNG2	0.008	0.027	-10000	0	-0.5	1	1
ARRB2	0.01	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.023	0.043	-10000	0	-0.34	2	2
G beta5/gamma2	-0.041	0.088	-10000	0	-0.24	55	55
PRKCH	-0.011	0.15	-10000	0	-0.35	57	57
DNM1	0.004	0.056	-10000	0	-0.52	4	4
TXA2/TP beta/beta Arrestin3	-0.003	0.016	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.002	0.076	-10000	0	-0.5	8	8
G12 family/GTP	-0.052	0.11	-10000	0	-0.3	56	56
ADRBK1	0.01	0	-10000	0	-10000	0	0
ADRBK2	0.008	0.027	-10000	0	-0.5	1	1
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.003	0.093	0.36	8	-10000	0	8
mol:NADP	-0.004	0.083	-10000	0	-0.52	9	9
RAB11A	0.01	0	-10000	0	-10000	0	0
PRKG1	-0.037	0.15	-10000	0	-0.5	32	32
mol:IP3	-0.016	0.17	-10000	0	-0.38	57	57
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.034	0.22	-10000	0	-0.52	57	57
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.027	0.075	-10000	0	-0.37	3	3
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.012	0.063	-10000	0	-0.41	5	5
RHOA	0.01	0	-10000	0	-10000	0	0
PTGIR	0.001	0.066	-10000	0	-0.5	6	6
PRKCB1	-0.017	0.16	-10000	0	-0.37	57	57
GNAQ	0.008	0.027	-10000	0	-0.5	1	1
mol:L-citrulline	-0.004	0.083	-10000	0	-0.52	9	9
TXA2/TXA2-R family	-0.034	0.22	-10000	0	-0.52	57	57
LCK	-0.005	0.045	-10000	0	-0.36	3	3
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.008	0.045	-10000	0	-0.5	1	1
TXA2-R family/G12 family/GDP/G beta/gamma	0.023	0.02	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.008	0.042	-10000	0	-0.5	1	1
MAPK14	0.006	0.1	-10000	0	-0.22	55	55
TGM2/GTP	-0.021	0.18	-10000	0	-0.42	57	57
MAPK11	0.004	0.11	-10000	0	-0.23	55	55
ARHGEF1	0.003	0.081	-10000	0	-0.18	23	23
GNAI2	0.01	0	-10000	0	-10000	0	0
JNK cascade	-0.016	0.17	-10000	0	-0.38	57	57
RAB11/GDP	0.009	0.001	-10000	0	-10000	0	0
ICAM1	-0.006	0.13	-10000	0	-0.29	55	55
cAMP biosynthetic process	-0.016	0.16	-10000	0	-0.35	57	57
Gq family/GTP/EBP50	0.014	0.052	-10000	0	-0.39	3	3
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.003	0.04	-10000	0	-0.37	2	2
GNB5	0.01	0	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
EGF/EGFR	0.011	0.078	-10000	0	-0.34	8	8
VCAM1	-0.007	0.13	-10000	0	-0.29	55	55
TP beta/Gq family/GDP/G beta5/gamma2	0.023	0.043	-10000	0	-0.34	2	2
platelet activation	0.006	0.14	-10000	0	-0.3	56	56
PGI2/IP	-0.006	0.047	-10000	0	-0.36	6	6
PRKACA	0.004	0.058	-10000	0	-0.27	13	13
Gq family/GDP/G beta5/gamma2	0.022	0.045	-10000	0	-0.3	3	3
TXA2/TP beta/beta Arrestin2	-0.002	0.014	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.013	0.055	-10000	0	-0.27	8	8
mol:DAG	-0.021	0.18	-10000	0	-0.42	57	57
EGFR	-0.005	0.087	-10000	0	-0.52	10	10
TXA2/TP alpha	-0.029	0.21	-10000	0	-0.48	57	57
Gq family/GTP	-0.009	0.054	-10000	0	-0.25	13	13
YES1	-0.003	0.04	-10000	0	-0.37	2	2
GNAI2/GTP	-0.008	0.044	-10000	0	-0.42	2	2
PGD2/DP	-0.008	0.054	-10000	0	-0.36	8	8
SLC9A3R1	0.007	0.04	-10000	0	-0.52	2	2
FYN	-0.003	0.04	-10000	0	-0.37	2	2
mol:NO	-0.004	0.083	-10000	0	-0.52	9	9
GNA15	0.01	0	-10000	0	-10000	0	0
PGK/cGMP	-0.035	0.1	-10000	0	-0.31	40	40
RhoA/GDP	0.009	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.011	0.053	-10000	0	-0.44	3	3
NOS3	-0.004	0.083	-10000	0	-0.52	9	9
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	-0.012	0.15	-10000	0	-0.35	58	58
PRKCB	-0.012	0.16	-10000	0	-0.36	56	56
PRKCE	-0.011	0.16	-10000	0	-0.35	56	56
PRKCD	-0.015	0.16	-10000	0	-0.38	55	55
PRKCG	-0.023	0.17	-10000	0	-0.38	57	57
muscle contraction	-0.028	0.21	-10000	0	-0.48	57	57
PRKCZ	-0.008	0.15	-10000	0	-0.34	56	56
ARR3	0.001	0.028	-10000	0	-0.52	1	1
TXA2/TP beta	-0.009	0.049	-10000	0	-0.47	2	2
PRKCQ	-0.032	0.17	-10000	0	-0.38	57	57
MAPKKK cascade	-0.028	0.2	-10000	0	-0.46	57	57
SELE	-0.022	0.16	-10000	0	-0.39	55	55
TP beta/GNAI2/GDP/G beta/gamma	-0.008	0.046	-10000	0	-0.45	2	2
ROCK1	0.01	0	-10000	0	-10000	0	0
GNA14	-0.008	0.093	-10000	0	-0.5	12	12
chemotaxis	-0.044	0.25	-10000	0	-0.6	55	55
GNA12	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
GNA11	0.008	0.027	-10000	0	-0.5	1	1
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.07	0.19	-10000	0	-0.52	54	54
NFATC2	0.004	0.16	-10000	0	-0.64	14	14
NFATC3	-0.012	0.081	-10000	0	-0.3	7	7
CD40LG	-0.086	0.36	-10000	0	-0.94	40	40
ITCH	-0.011	0.1	-10000	0	-10000	0	0
CBLB	-0.011	0.1	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.13	0.24	-10000	0	-0.94	16	16
JUNB	0.007	0.039	-10000	0	-0.5	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.052	0.11	-10000	0	-10000	0	0
T cell anergy	-0.06	0.16	-10000	0	-0.38	68	68
TLE4	0.021	0.15	-10000	0	-0.8	7	7
Jun/NFAT1-c-4/p21SNFT	-0.12	0.3	-10000	0	-0.94	36	36
AP-1/NFAT1-c-4	-0.11	0.4	-10000	0	-1.1	37	37
IKZF1	0.022	0.15	-10000	0	-0.81	7	7
T-helper 2 cell differentiation	0.006	0.19	-10000	0	-0.84	9	9
AP-1/NFAT1	-0.052	0.13	-10000	0	-0.48	18	18
CALM1	-0.011	0.067	-10000	0	-10000	0	0
EGR2	-0.054	0.4	-10000	0	-1.4	21	21
EGR3	-0.098	0.48	-10000	0	-1.4	41	41
NFAT1/FOXP3	-0.05	0.18	-10000	0	-0.5	19	19
EGR1	-0.028	0.13	-10000	0	-0.5	26	26
JUN	0.004	0.042	-10000	0	-0.5	2	2
EGR4	-0.038	0.15	-10000	0	-0.52	31	31
mol:Ca2+	-0.023	0.071	-10000	0	-10000	0	0
GBP3	0.009	0.18	-10000	0	-0.72	16	16
FOSL1	-0.028	0.14	-10000	0	-0.52	25	25
NFAT1-c-4/MAF/IRF4	-0.12	0.3	-10000	0	-0.92	35	35
DGKA	0.026	0.12	-10000	0	-0.66	5	5
CREM	0.009	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.14	0.34	-10000	0	-1	37	37
CTLA4	-0.029	0.16	-10000	0	-0.6	10	10
NFAT1-c-4 (dimer)/EGR1	-0.13	0.34	-10000	0	-1	37	37
NFAT1-c-4 (dimer)/EGR4	-0.13	0.32	-10000	0	-0.96	35	35
FOS	-0.033	0.14	-10000	0	-0.52	27	27
IFNG	-0.087	0.22	-10000	0	-0.9	17	17
T cell activation	0.008	0.2	-10000	0	-0.7	12	12
MAF	0.008	0.027	-10000	0	-0.5	1	1
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.035	0.28	0.95	18	-10000	0	18
TNF	-0.08	0.35	-10000	0	-0.94	38	38
FASLG	-0.12	0.49	-10000	0	-1.3	47	47
TBX21	-0.016	0.11	-10000	0	-0.51	17	17
BATF3	0.008	0.028	-10000	0	-0.52	1	1
PRKCQ	-0.058	0.18	-10000	0	-0.5	48	48
PTPN1	0.027	0.12	-10000	0	-0.66	5	5
NFAT1-c-4/ICER1	-0.11	0.31	-10000	0	-0.95	35	35
GATA3	0.008	0.039	-10000	0	-0.51	2	2
T-helper 1 cell differentiation	-0.069	0.23	-10000	0	-0.87	17	17
IL2RA	-0.13	0.22	-10000	0	-0.76	23	23
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.027	0.12	-10000	0	-0.66	5	5
E2F1	0.005	0.069	-10000	0	-0.52	6	6
PPARG	-0.06	0.18	-10000	0	-0.5	48	48
SLC3A2	0.027	0.12	-10000	0	-0.66	5	5
IRF4	-0.01	0.1	-10000	0	-0.52	13	13
PTGS2	-0.098	0.38	-10000	0	-0.99	41	41
CSF2	-0.092	0.37	-10000	0	-0.95	41	41
JunB/Fra1/NFAT1-c-4	-0.12	0.3	-10000	0	-0.93	35	35
IL4	0.005	0.19	-10000	0	-0.89	9	9
IL5	-0.078	0.34	-10000	0	-0.92	37	37
IL2	0.007	0.2	-10000	0	-0.71	12	12
IL3	-0.027	0.047	-10000	0	-10000	0	0
RNF128	-0.082	0.24	-10000	0	-0.58	68	68
NFATC1	-0.036	0.28	-10000	0	-0.96	18	18
CDK4	0.009	0.17	0.6	8	-10000	0	8
PTPRK	0.027	0.12	-10000	0	-0.73	4	4
IL8	-0.086	0.35	-10000	0	-0.91	38	38
POU2F1	0.01	0.001	-10000	0	-10000	0	0

×

EGFR-dependent Endothelin signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.01	0	-9999	-10000	0	0
EGFR	-0.005	0.087	-9999	-0.52	10	10
EGF/EGFR	-0.086	0.13	-9999	-0.29	72	72
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.054	0.11	-9999	-0.51	2	2
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.007	0.039	-9999	-0.5	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.091	0.21	-9999	-0.52	67	67
EGF/EGFR dimer/SHC	-0.067	0.13	-9999	-0.32	75	75
mol:GDP	-0.054	0.11	-9999	-0.5	2	2
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.057	0.17	-9999	-0.5	46	46
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.049	0.096	-9999	-0.47	2	2
SHC1	0.01	0	-9999	-10000	0	0
HRAS/GDP	-0.05	0.098	-9999	-0.48	2	2
FRAP1	-0.028	0.11	-9999	-0.49	2	2
EGF/EGFR dimer	-0.08	0.16	-9999	-0.38	75	75
SOS1	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.048	0.12	-9999	-0.36	48	48

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.12	0.38	-10000	0	-1	30	30
IL23A	-0.15	0.41	-10000	0	-1.2	27	27
NF kappa B1 p50/RelA/I kappa B alpha	-0.2	0.32	-10000	0	-1	31	31
positive regulation of T cell mediated cytotoxicity	-0.14	0.42	-10000	0	-1.2	31	31
ITGA3	-0.13	0.39	-10000	0	-1.1	31	31
IL17F	-0.067	0.27	-10000	0	-0.7	24	24
IL12B	0.01	0.063	-10000	0	-0.53	4	4
STAT1 (dimer)	-0.13	0.4	-10000	0	-1.1	31	31
CD4	-0.12	0.38	-10000	0	-1.1	29	29
IL23	-0.15	0.4	-10000	0	-1.1	28	28
IL23R	0	0.082	-10000	0	-10000	0	0
IL1B	-0.16	0.44	-10000	0	-1.2	33	33
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.12	0.37	-10000	0	-1	27	27
TYK2	0.01	0.019	-10000	0	-10000	0	0
STAT4	0.01	0	-10000	0	-10000	0	0
STAT3	0.01	0	-10000	0	-10000	0	0
IL18RAP	-0.014	0.11	-10000	0	-0.5	16	16
IL12RB1	-0.006	0.096	-10000	0	-0.53	11	11
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.002	0.073	-10000	0	-0.38	11	11
IL23R/JAK2	0.003	0.1	-10000	0	-10000	0	0
positive regulation of chronic inflammatory response	-0.14	0.42	-10000	0	-1.2	31	31
natural killer cell activation	0.001	0.007	0.037	1	-10000	0	1
JAK2	0.017	0.024	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
NFKB1	0.009	0.003	-10000	0	-10000	0	0
RELA	0.009	0.003	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.14	0.38	-10000	0	-1.1	28	28
ALOX12B	-0.14	0.39	-10000	0	-1	31	31
CXCL1	-0.14	0.41	-10000	0	-1.2	30	30
T cell proliferation	-0.14	0.42	-10000	0	-1.2	31	31
NFKBIA	0.009	0.003	-10000	0	-10000	0	0
IL17A	-0.046	0.23	-10000	0	-0.56	18	18
PI3K	-0.2	0.33	-10000	0	-1.1	31	31
IFNG	-0.007	0.032	-10000	0	-0.11	6	6
STAT3 (dimer)	-0.19	0.31	-10000	0	-1	31	31
IL18R1	-0.011	0.1	-10000	0	-0.5	14	14
IL23/IL23R/JAK2/TYK2/SOCS3	-0.057	0.24	-10000	0	-0.71	14	14
IL18/IL18R	-0.021	0.11	-10000	0	-0.35	31	31
macrophage activation	-0.014	0.016	-10000	0	-0.044	24	24
TNF	-0.15	0.44	-10000	0	-1.2	31	31
STAT3/STAT4	-0.2	0.33	-10000	0	-1.1	31	31
STAT4 (dimer)	-0.13	0.4	-10000	0	-1.1	31	31
IL18	-0.002	0.076	-10000	0	-0.5	8	8
IL19	-0.12	0.37	-10000	0	-1	29	29
STAT5A (dimer)	-0.14	0.4	-10000	0	-1.1	31	31
STAT1	0.01	0	-10000	0	-10000	0	0
SOCS3	0.007	0.039	-10000	0	-0.5	2	2
CXCL9	-0.14	0.4	-10000	0	-1.1	32	32
MPO	-0.12	0.39	-10000	0	-1.2	24	24
positive regulation of humoral immune response	-0.14	0.42	-10000	0	-1.2	31	31
IL23/IL23R/JAK2/TYK2	-0.15	0.45	-10000	0	-1.3	31	31
IL6	-0.27	0.56	-10000	0	-1.2	83	83
STAT5A	0.008	0.027	-10000	0	-0.5	1	1
IL2	0.006	0.009	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.001	0.007	0.037	1	-10000	0	1
CD3E	-0.12	0.38	-10000	0	-1.1	28	28
keratinocyte proliferation	-0.14	0.42	-10000	0	-1.2	31	31
NOS2	-0.17	0.46	-10000	0	-1.1	52	52

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.008	0.027	-9999	-0.5	1	1
PLK4	-0.025	0.13	-9999	-0.52	23	23
regulation of centriole replication	-0.008	0.098	-9999	-0.37	24	24

×

PDGFR-alpha signaling pathway

Figure S41. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S41. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.004	0.048	-9999	-0.5	3	3
PDGF/PDGFRA/CRKL	-0.003	0.032	-9999	-0.34	3	3
positive regulation of JUN kinase activity	-0.002	0.022	-9999	-10000	0	0
CRKL	0.01	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.087	0.15	-9999	-0.36	84	84
AP1	-0.07	0.23	-9999	-0.87	27	27
mol:IP3	0.013	0.038	-9999	-0.36	3	3
PLCG1	0.013	0.038	-9999	-0.36	3	3
PDGF/PDGFRA/alphaV Integrin	-0.003	0.032	-9999	-0.34	3	3
RAPGEF1	0.01	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
mol:Ca2+	0.013	0.038	-9999	-0.35	3	3
CAV3	-0.11	0.21	-9999	-0.5	81	81
CAV1	-0.3	0.25	-9999	-0.5	214	214
SHC/Grb2/SOS1	-0.002	0.023	-9999	-10000	0	0
PDGF/PDGFRA/Shf	-0.005	0.042	-9999	-0.36	5	5
FOS	-0.034	0.24	-9999	-0.86	27	27
JUN	-0.007	0.031	-9999	-0.36	2	2
oligodendrocyte development	-0.003	0.031	-9999	-0.34	3	3
GRB2	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
mol:DAG	0.013	0.038	-9999	-0.36	3	3
PDGF/PDGFRA	0.004	0.048	-9999	-0.5	3	3
actin cytoskeleton reorganization	-0.004	0.037	-9999	-0.35	4	4
SRF	0.018	0.007	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
PI3K	-0.002	0.026	-9999	-0.28	3	3
PDGF/PDGFRA/Crk/C3G	-0.002	0.026	-9999	-0.28	3	3
JAK1	0.015	0.034	-9999	-0.34	3	3
ELK1/SRF	-0.003	0.023	-9999	-10000	0	0
SHB	0.008	0.027	-9999	-0.5	1	1
SHF	0.007	0.04	-9999	-0.52	2	2
CSNK2A1	0.004	0.014	-9999	-10000	0	0
GO:0007205	0.014	0.041	-9999	-0.38	3	3
SOS1	0.01	0	-9999	-10000	0	0
Ras protein signal transduction	-0.002	0.022	-9999	-10000	0	0
PDGF/PDGFRA/SHB	-0.004	0.037	-9999	-0.35	4	4
PDGF/PDGFRA/Caveolin-1	-0.22	0.18	-9999	-0.37	214	214
ITGAV	0.01	0	-9999	-10000	0	0
ELK1	0.017	0.041	-9999	-0.32	3	3
PIK3CA	0.01	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.003	0.032	-9999	-0.34	3	3
JAK-STAT cascade	0.015	0.034	-9999	-0.34	3	3
cell proliferation	-0.005	0.042	-9999	-0.36	5	5

×

Wnt 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
Noncanonical Wnts/FZD	-0.037	0.13	-9999	-0.48	13	13
FZD6	0.008	0.027	-9999	-0.5	1	1
WNT6	-0.023	0.13	-9999	-0.52	21	21
WNT4	-0.025	0.13	-9999	-0.51	24	24
FZD3	0.008	0.028	-9999	-0.52	1	1
WNT5A	0.004	0.054	-9999	-0.5	4	4
WNT11	-0.066	0.18	-9999	-0.5	52	52

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.14	0.22	-10000	0	-0.64	14	14
CRP	-0.15	0.23	-10000	0	-0.72	10	10
cell cycle arrest	-0.17	0.25	-10000	0	-0.6	43	43
TIMP1	-0.11	0.2	-10000	0	-0.64	9	9
IL6ST	-0.005	0.077	-10000	0	-0.51	8	8
Rac1/GDP	-0.062	0.14	-10000	0	-0.42	15	15
AP1	-0.001	0.097	-10000	0	-0.59	3	3
GAB2	0.006	0.055	-10000	0	-0.5	4	4
TNFSF11	-0.19	0.25	-10000	0	-0.65	32	32
HSP90B1	-0.004	0.044	-10000	0	-10000	0	0
GAB1	0.01	0.028	-10000	0	-0.5	1	1
MAPK14	-0.036	0.13	-10000	0	-0.53	7	7
AKT1	0.036	0.034	-10000	0	-10000	0	0
FOXO1	0.042	0.031	-10000	0	-10000	0	0
MAP2K6	-0.054	0.13	-10000	0	-0.43	11	11
mol:GTP	-0.002	0.002	-10000	0	-10000	0	0
MAP2K4	-0.076	0.16	-10000	0	-0.48	12	12
MITF	-0.06	0.13	-10000	0	-0.32	39	39
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.01	0	-10000	0	-10000	0	0
A2M	-0.082	0.34	-10000	0	-1.3	27	27
CEBPB	0.015	0.003	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.008	0.084	0.22	2	-0.56	3	5
STAT3	-0.17	0.26	-10000	0	-0.63	43	43
STAT1	-0.001	0.011	-10000	0	-10000	0	0
CEBPD	-0.14	0.24	-10000	0	-0.78	11	11
PIK3CA	0.011	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
JUN	0.007	0.039	-10000	0	-0.5	2	2
PIAS3/MITF	-0.053	0.12	-10000	0	-0.38	12	12
MAPK11	-0.038	0.13	-10000	0	-0.51	9	9
STAT3 (dimer)/FOXO1	-0.11	0.23	-10000	0	-0.68	18	18
GRB2/SOS1/GAB family	-0.052	0.11	0.18	2	-0.45	11	13
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.057	0.14	-10000	0	-0.32	51	51
GRB2	0.011	0.004	-10000	0	-10000	0	0
JAK2	0.01	0	-10000	0	-10000	0	0
LBP	-0.13	0.2	-10000	0	-0.6	11	11
PIK3R1	0.011	0	-10000	0	-10000	0	0
JAK1	0.009	0.004	-10000	0	-10000	0	0
MYC	-0.14	0.23	-10000	0	-0.75	10	10
FGG	-0.33	0.46	-10000	0	-0.98	110	110
macrophage differentiation	-0.17	0.25	-10000	0	-0.6	43	43
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.064	0.12	-10000	0	-0.42	6	6
JUNB	-0.14	0.22	-10000	0	-0.7	12	12
FOS	-0.03	0.14	-10000	0	-0.5	27	27
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.069	0.13	-10000	0	-0.33	48	48
STAT1/PIAS1	-0.074	0.13	-10000	0	-0.33	40	40
GRB2/SOS1/GAB family/SHP2/PI3K	0.018	0.038	-10000	0	-0.26	2	2
STAT3 (dimer)	-0.17	0.26	-10000	0	-0.63	43	43
PRKCD	-0.092	0.18	-10000	0	-0.57	11	11
IL6R	-0.003	0.078	-10000	0	-0.51	8	8
SOCS3	-0.025	0.14	-10000	0	-0.97	3	3
gp130 (dimer)/JAK1/JAK1/LMO4	0.005	0.051	-10000	0	-0.3	8	8
Rac1/GTP	-0.094	0.12	-10000	0	-0.36	38	38
HCK	-0.01	0.1	-10000	0	-0.5	14	14
MAPKKK cascade	0.01	0.085	-10000	0	-0.59	4	4
bone resorption	-0.18	0.24	-10000	0	-0.62	32	32
IRF1	-0.14	0.22	-10000	0	-0.64	14	14
mol:GDP	-0.065	0.14	-10000	0	-0.34	40	40
SOS1	0.011	0.007	-10000	0	-10000	0	0
VAV1	-0.065	0.14	-10000	0	-0.35	40	40
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.032	0.13	-10000	0	-0.45	11	11
PTPN11	-0.001	0.01	-10000	0	-10000	0	0
IL6/IL6RA	-0.079	0.16	-10000	0	-0.37	82	82
gp130 (dimer)/TYK2/TYK2/LMO4	0.003	0.049	-10000	0	-0.3	8	8
gp130 (dimer)/JAK2/JAK2/LMO4	0.003	0.049	-10000	0	-0.3	8	8
IL6	-0.1	0.21	-10000	0	-0.51	76	76
PIAS3	0.01	0	-10000	0	-10000	0	0
PTPRE	0.011	0.04	-10000	0	-0.49	2	2
PIAS1	0.01	0	-10000	0	-10000	0	0
RAC1	0.009	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.059	0.12	-10000	0	-0.28	61	61
LMO4	0.006	0.008	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.19	0.21	-10000	0	-0.59	43	43
MCL1	0.042	0.03	-10000	0	-10000	0	0

×

ErbB4 signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.067	0.14	-10000	0	-0.42	25	25
epithelial cell differentiation	-0.072	0.12	-10000	0	-0.45	12	12
ITCH	0.023	0.018	-10000	0	-10000	0	0
WWP1	-0.018	0.069	-10000	0	-10000	0	0
FYN	0.01	0	-10000	0	-10000	0	0
EGFR	-0.005	0.087	-10000	0	-0.52	10	10
PRL	-0.011	0.087	-10000	0	-0.52	10	10
neuron projection morphogenesis	-0.02	0.11	-10000	0	-0.4	1	1
PTPRZ1	-0.12	0.23	-10000	0	-0.52	88	88
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.061	0.1	-10000	0	-0.44	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.061	0.13	-10000	0	-0.37	35	35
ADAM17	0.023	0.018	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.032	0.089	-10000	0	-0.38	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.14	0.17	-10000	0	-0.41	60	60
NCOR1	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.071	0.11	-10000	0	-0.48	1	1
GRIN2B	-0.053	0.13	-10000	0	-0.5	3	3
ErbB4/ErbB2/betacellulin	-0.033	0.063	-10000	0	-0.35	1	1
STAT1	0.01	0	-10000	0	-10000	0	0
HBEGF	-0.067	0.18	-10000	0	-0.5	53	53
PRLR	-0.053	0.17	-10000	0	-0.52	42	42
E4ICDs/ETO2	-0.047	0.12	-10000	0	-0.42	16	16
axon guidance	0.007	0.076	-10000	0	-10000	0	0
NEDD4	0.021	0.032	-10000	0	-0.48	1	1
Prolactin receptor/Prolactin receptor/Prolactin	-0.055	0.13	-10000	0	-0.38	51	51
CBFA2T3	-0.032	0.14	-10000	0	-0.5	29	29
ErbB4/ErbB2/HBEGF	-0.064	0.1	-10000	0	-0.48	1	1
MAPK3	-0.027	0.11	-10000	0	-0.41	1	1
STAT1 (dimer)	-0.023	0.074	-10000	0	-10000	0	0
MAPK1	-0.027	0.11	-10000	0	-0.41	1	1
JAK2	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.073	0.12	-10000	0	-0.49	2	2
NRG1	-0.045	0.15	-10000	0	-0.35	65	65
NRG3	-0.19	0.25	-10000	0	-0.5	137	137
NRG2	-0.055	0.17	-10000	0	-0.5	44	44
NRG4	-0.038	0.15	-10000	0	-0.52	31	31
heart development	0.007	0.076	-10000	0	-10000	0	0
neural crest cell migration	-0.072	0.11	-10000	0	-0.49	2	2
ERBB2	0.024	0.032	-10000	0	-0.37	2	2
WWOX/E4ICDs	-0.023	0.074	-10000	0	-10000	0	0
SHC1	0.01	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.067	0.11	-10000	0	-0.41	17	17
apoptosis	0.2	0.22	0.54	77	-10000	0	77
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.06	0.13	-10000	0	-0.41	24	24
ErbB4/ErbB2/epiregulin	-0.11	0.13	-10000	0	-0.36	25	25
ErbB4/ErbB4/betacellulin/betacellulin	-0.03	0.094	-10000	0	-0.41	8	8
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.1	0.14	-10000	0	-0.53	13	13
MDM2	-0.022	0.079	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.065	0.11	-10000	0	-0.43	1	1
STAT5A	0.012	0.073	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.079	0.12	-10000	0	-0.53	5	5
DLG4	0.01	0	-10000	0	-10000	0	0
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.039	0.055	-10000	0	-10000	0	0
STAT5A (dimer)	-0.076	0.12	-10000	0	-0.49	11	11
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.011	0.068	-10000	0	-10000	0	0
LRIG1	0.007	0.039	-10000	0	-0.5	2	2
EREG	-0.16	0.24	-10000	0	-0.51	111	111
BTC	-0.003	0.081	-10000	0	-0.5	9	9
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.004	0.074	-10000	0	-10000	0	0
ERBB4	-0.032	0.089	-10000	0	-0.38	1	1
STAT5B	0.01	0	-10000	0	-10000	0	0
YAP1	0	0.005	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.049	0.085	-10000	0	-0.35	9	9
glial cell differentiation	0.039	0.055	-10000	0	-10000	0	0
WWOX	0.01	0	-10000	0	-10000	0	0
cell proliferation	-0.058	0.15	-10000	0	-0.47	18	18

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.012	0.1	0.5	15	-10000	0	15
PI3K Class IB/PDE3B	-0.012	0.1	-10000	0	-0.5	15	15
PDE3B	-0.012	0.1	-10000	0	-0.5	15	15

×

HIF-2-alpha transcription factor network

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
MMP14	-0.009	0.036	-10000	0	-10000	0	0
oxygen homeostasis	0	0.014	-10000	0	-10000	0	0
TCEB2	0.01	0	-10000	0	-10000	0	0
TCEB1	0.007	0.04	-10000	0	-0.52	2	2
VHL/Elongin B/Elongin C/HIF2A	-0.07	0.12	-10000	0	-0.41	19	19
EPO	-0.039	0.22	-10000	0	-0.55	18	18
FIH (dimer)	0.01	0.012	-10000	0	-10000	0	0
APEX1	0.011	0.012	-10000	0	-10000	0	0
SERPINE1	-0.063	0.26	-10000	0	-0.67	22	22
FLT1	-0.008	0.033	-10000	0	-10000	0	0
ADORA2A	-0.056	0.24	-10000	0	-0.62	21	21
germ cell development	-0.072	0.26	-10000	0	-0.63	24	24
SLC11A2	-0.059	0.25	-10000	0	-0.64	20	20
BHLHE40	-0.059	0.25	-10000	0	-0.64	21	21
HIF1AN	0.01	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.093	0.14	-10000	0	-0.44	30	30
ETS1	0.022	0.003	-10000	0	-10000	0	0
CITED2	-0.01	0.055	-10000	0	-0.96	1	1
KDR	-0.027	0.16	-10000	0	-1.2	7	7
PGK1	-0.059	0.25	-10000	0	-0.64	20	20
SIRT1	0.01	0	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.075	0.29	-10000	0	-0.74	23	23
EPAS1	-0.051	0.17	-10000	0	-0.4	34	34
SP1	0.016	0.001	-10000	0	-10000	0	0
ABCG2	-0.085	0.3	-10000	0	-0.73	34	34
EFNA1	-0.06	0.25	-10000	0	-0.65	20	20
FXN	-0.056	0.24	-10000	0	-0.62	20	20
POU5F1	-0.075	0.27	-10000	0	-0.66	24	24
neuron apoptosis	0.073	0.28	0.7	24	-10000	0	24
EP300	0.01	0	-10000	0	-10000	0	0
EGLN3	-0.14	0.24	-10000	0	-0.53	99	99
EGLN2	0.01	0.012	-10000	0	-10000	0	0
EGLN1	0.01	0.012	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.002	0.023	-10000	0	-0.31	2	2
VHL	0.01	0	-10000	0	-10000	0	0
ARNT	0.011	0.012	-10000	0	-10000	0	0
SLC2A1	-0.14	0.32	-10000	0	-0.66	59	59
TWIST1	-0.1	0.3	-10000	0	-0.67	42	42
ELK1	0.016	0.005	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.091	0.14	-10000	0	-0.44	28	28
VEGFA	-0.059	0.25	-10000	0	-0.64	20	20
CREBBP	0.01	0	-10000	0	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.009	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.031	0.086	-10000	0	-0.27	41	41
regulation of S phase of mitotic cell cycle	-0.004	0.079	-10000	0	-0.23	39	39
GNAO1	0.005	0.048	-10000	0	-0.51	3	3
HRAS	0.01	0.001	-10000	0	-10000	0	0
SHBG/T-DHT	-0.002	0.024	-10000	0	-0.32	2	2
PELP1	0.01	0.001	-10000	0	-10000	0	0
AKT1	0.009	0	-10000	0	-10000	0	0
MAP2K1	0.004	0.088	-10000	0	-0.32	9	9
T-DHT/AR	-0.041	0.12	-10000	0	-0.37	40	40
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-0.007	27	27
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.007	0.039	-10000	0	-0.5	2	2
mol:GDP	-0.044	0.12	-10000	0	-0.4	39	39
cell proliferation	0	0.14	-10000	0	-0.41	27	27
PIK3CA	0.01	0	-10000	0	-10000	0	0
FOS	-0.027	0.22	-10000	0	-0.79	27	27
mol:Ca2+	-0.01	0.022	-10000	0	-0.089	13	13
MAPK3	0.003	0.11	-10000	0	-0.46	9	9
MAPK1	0.004	0.07	-10000	0	-0.26	9	9
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.004	27	27
cAMP biosynthetic process	0.007	0.031	-10000	0	-0.31	2	2
GNG2	0.008	0.027	-10000	0	-0.5	1	1
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	27	27
HRAS/GTP	-0.029	0.077	-10000	0	-0.29	9	9
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.01	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	27	27
PI3K	0	0	-10000	0	-10000	0	0
apoptosis	0.003	0.13	0.42	27	-10000	0	27
T-DHT/AR/PELP1	-0.034	0.096	-10000	0	-0.3	40	40
HRAS/GDP	-0.041	0.12	-10000	0	-0.37	39	39
CREB1	-0.005	0.14	-10000	0	-0.45	27	27
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
AR	-0.049	0.16	-10000	0	-0.51	40	40
GNB1	0.01	0	-10000	0	-10000	0	0
RAF1	-0.001	0.086	-10000	0	-0.3	9	9
RAC1-CDC42/GDP	-0.039	0.11	-10000	0	-0.35	39	39
T-DHT/AR/PELP1/Src	-0.031	0.086	-10000	0	-0.27	40	40
MAP2K2	0.004	0.088	-10000	0	-0.32	9	9
T-DHT/AR/PELP1/Src/PI3K	-0.004	0.08	-10000	0	-0.23	39	39
GNAZ	-0.031	0.14	-10000	0	-0.5	28	28
SHBG	0.006	0.04	-10000	0	-0.52	2	2
Gi family/GNB1/GNG2/GDP	0.007	0.08	-10000	0	-0.43	3	3
mol:T-DHT	0	0.001	-10000	0	-0.003	18	18
RAC1	0.01	0	-10000	0	-10000	0	0
GNRH1	0.005	0.04	-10000	0	-0.36	4	4
Gi family/GTP	-0.032	0.083	-10000	0	-0.37	12	12
CDC42	0.01	0	-10000	0	-10000	0	0

×

Regulation of Androgen receptor activity

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
HDAC1	0.018	0.001	-9999	-10000	0	0
SMARCC1	0.003	0.006	-9999	-10000	0	0
REL	0.01	0.001	-9999	-10000	0	0
HDAC7	0.024	0.09	-9999	-0.43	2	2
JUN	0.007	0.039	-9999	-0.5	2	2
EP300	0.01	0	-9999	-10000	0	0
KAT2B	0.01	0	-9999	-10000	0	0
KAT5	0.01	0	-9999	-10000	0	0
MAPK14	0.006	0.072	-9999	-0.37	12	12
FOXO1	0.01	0	-9999	-10000	0	0
T-DHT/AR	0.022	0.095	-9999	-0.4	4	4
MAP2K6	-0.008	0.097	-9999	-0.52	12	12
BRM/BAF57	-0.003	0.033	-9999	-0.36	3	3
MAP2K4	0.01	0.004	-9999	-10000	0	0
SMARCA2	0.005	0.047	-9999	-0.5	3	3
PDE9A	-0.046	0.16	-9999	-0.77	11	11
NCOA2	0.007	0.039	-9999	-0.5	2	2
CEBPA	-0.019	0.12	-9999	-0.51	20	20
EHMT2	0.01	0.001	-9999	-10000	0	0
cell proliferation	0.019	0.14	-9999	-0.44	15	15
NR0B1	-0.11	0.21	-9999	-0.52	74	74
EGR1	-0.028	0.13	-9999	-0.5	26	26
RXRs/9cRA	-0.13	0.13	-9999	-0.27	177	177
AR/RACK1/Src	0	0.065	-9999	-0.4	1	1
AR/GR	-0.002	0.089	-9999	-0.29	16	16
GNB2L1	0.01	0.001	-9999	-10000	0	0
PKN1	0.01	0	-9999	-10000	0	0
RCHY1	0.01	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.001	-9999	-10000	0	0
MAPK8	0.019	0.01	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	0	0.067	-9999	-0.41	1	1
SRC	0.024	0.057	-9999	-0.31	1	1
NR3C1	0.01	0	-9999	-10000	0	0
KLK3	-0.067	0.11	-9999	-0.46	6	6
APPBP2	0.01	0.004	-9999	-10000	0	0
TRIM24	0.01	0.001	-9999	-10000	0	0
T-DHT/AR/TIP60	0.015	0.068	-9999	-0.44	1	1
TMPRSS2	-0.11	0.31	-9999	-1.1	32	32
RXRG	-0.25	0.26	-9999	-0.5	177	177
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.01	0	-9999	-10000	0	0
RXRB	0.01	0	-9999	-10000	0	0
CARM1	0.009	0.002	-9999	-10000	0	0
NR2C2	0.01	0	-9999	-10000	0	0
KLK2	0.017	0.096	-9999	-0.42	5	5
AR	-0.006	0.1	-9999	-0.27	39	39
SENP1	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
MDM2	0.007	0.04	-9999	-0.52	2	2
SRY	0.001	0.004	-9999	-10000	0	0
GATA2	-0.037	0.15	-9999	-0.5	32	32
MYST2	0.01	0	-9999	-10000	0	0
HOXB13	-0.18	0.25	-9999	-0.52	123	123
T-DHT/AR/RACK1/Src	0.021	0.068	-9999	-0.42	1	1
positive regulation of transcription	-0.037	0.15	-9999	-0.5	32	32
DNAJA1	0.01	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.01	-9999	-10000	0	0
NCOA1	0.012	0.003	-9999	-10000	0	0
SPDEF	-0.17	0.25	-9999	-0.52	120	120
T-DHT/AR/TIF2	0.029	0.049	-9999	-0.26	1	1
T-DHT/AR/Hsp90	0.016	0.068	-9999	-0.37	2	2
GSK3B	0.009	0.003	-9999	-10000	0	0
NR2C1	0.01	0	-9999	-10000	0	0
mol:T-DHT	0.019	0.06	-9999	-0.31	4	4
SIRT1	0.01	0	-9999	-10000	0	0
ZMIZ2	0.01	0.002	-9999	-10000	0	0
POU2F1	0.015	0.024	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.061	0.13	-9999	-0.38	25	25
CREBBP	0.01	0	-9999	-10000	0	0
SMARCE1	0.01	0.001	-9999	-10000	0	0

×

Syndecan-2-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
Syndecan-2/Fibronectin	0.013	0.049	-9999	-0.34	6	6
EPHB2	-0.058	0.18	-9999	-0.52	45	45
Syndecan-2/TACI	-0.01	0.092	-9999	-0.31	31	31
LAMA1	-0.023	0.13	-9999	-0.52	22	22
Syndecan-2/alpha2 ITGB1	-0.059	0.11	-9999	-0.5	4	4
HRAS	0.01	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.003	0.028	-9999	-0.3	3	3
ITGA5	0.008	0.028	-9999	-0.52	1	1
BAX	0.03	0.026	-9999	-10000	0	0
EPB41	0.01	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.002	0.024	-9999	-0.26	3	3
LAMA3	-0.092	0.2	-9999	-0.5	70	70
EZR	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.089	0.2	-9999	-0.5	68	68
Syndecan-2/MMP2	0.016	0.029	-9999	-0.29	3	3
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.014	0.07	-9999	-0.37	13	13
dendrite morphogenesis	-0.025	0.11	-9999	-0.31	48	48
Syndecan-2/GM-CSF	-0.009	0.09	-9999	-0.3	31	31
determination of left/right symmetry	0.013	0.034	-9999	-0.36	3	3
Syndecan-2/PKC delta	0.016	0.029	-9999	-0.29	3	3
GNB2L1	0.01	0	-9999	-10000	0	0
MAPK3	0	0.082	-9999	-0.26	31	31
MAPK1	0	0.082	-9999	-0.26	31	31
Syndecan-2/RACK1	-0.002	0.022	-9999	-0.24	3	3
NF1	0.01	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.013	0.034	-9999	-0.36	3	3
ITGA2	-0.01	0.1	-9999	-0.52	13	13
MAPK8	0.025	0.029	-9999	-0.29	3	3
Syndecan-2/alpha2/beta1 Integrin	-0.027	0.087	-9999	-0.29	26	26
Syndecan-2/Kininogen	-0.017	0.088	-9999	-0.31	29	29
ITGB1	0.01	0	-9999	-10000	0	0
SRC	0.027	0.023	-9999	-10000	0	0
Syndecan-2/CASK/Protein 4.1	-0.002	0.024	-9999	-0.27	3	3
extracellular matrix organization	0.016	0.029	-9999	-0.29	3	3
actin cytoskeleton reorganization	0.013	0.048	-9999	-0.34	6	6
Syndecan-2/Caveolin-2/Ras	-0.053	0.1	-9999	-0.26	71	71
Syndecan-2/Laminin alpha3	-0.046	0.13	-9999	-0.3	73	73
Syndecan-2/RasGAP	-0.002	0.021	-9999	-10000	0	0
alpha5/beta1 Integrin	-0.001	0.02	-9999	-0.37	1	1
PRKCD	0.01	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.025	0.11	-9999	-0.31	48	48
GO:0007205	0.003	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.002	0.02	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
SDCBP	0.01	0	-9999	-10000	0	0
TNFRSF13B	-0.032	0.14	-9999	-0.52	28	28
RASA1	0.01	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.014	0.07	-9999	-0.37	13	13
Syndecan-2/Synbindin	0.016	0.029	-9999	-0.29	3	3
TGFB1	0.01	0	-9999	-10000	0	0
CASP3	0.023	0.026	-9999	-0.26	3	3
FN1	0.004	0.054	-9999	-0.5	4	4
Syndecan-2/IL8	-0.001	0.079	-9999	-0.31	22	22
SDC2	0.013	0.034	-9999	-0.36	3	3
KNG1	-0.034	0.14	-9999	-0.52	26	26
Syndecan-2/Neurofibromin	0.016	0.029	-9999	-0.29	3	3
TRAPPC4	0.01	0	-9999	-10000	0	0
CSF2	-0.032	0.14	-9999	-0.51	28	28
Syndecan-2/TGFB1	0.016	0.029	-9999	-0.29	3	3
Syndecan-2/Syntenin/PI-4-5-P2	-0.002	0.024	-9999	-0.27	3	3
Syndecan-2/Ezrin	-0.002	0.024	-9999	-0.26	3	3
PRKACA	0.023	0.026	-9999	-0.26	3	3
angiogenesis	-0.001	0.078	-9999	-0.3	22	22
MMP2	0.01	0	-9999	-10000	0	0
IL8	-0.019	0.12	-9999	-0.52	19	19
calcineurin-NFAT signaling pathway	-0.01	0.092	-9999	-0.3	31	31

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.011	0.062	-9999	-0.37	10	10
VLDLR	-0.002	0.076	-9999	-0.5	8	8
CRKL	0.01	0	-9999	-10000	0	0
LRPAP1	0.01	0	-9999	-10000	0	0
FYN	0.01	0	-9999	-10000	0	0
ITGA3	0.005	0.047	-9999	-0.5	3	3
RELN/VLDLR/Fyn	-0.048	0.12	-9999	-0.32	53	53
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.001	0.013	-9999	-10000	0	0
AKT1	-0.011	0.094	-9999	-0.4	5	5
MAP2K7	0.01	0	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0
DAB1	-0.001	0.063	-9999	-0.52	5	5
RELN/LRP8/DAB1	-0.048	0.11	-9999	-0.28	60	60
LRPAP1/LRP8	-0.008	0.055	-9999	-0.37	8	8
RELN/LRP8/DAB1/Fyn	-0.044	0.099	-9999	-0.27	41	41
DAB1/alpha3/beta1 Integrin	-0.045	0.099	-9999	-0.46	7	7
long-term memory	-0.096	0.14	-9999	-0.52	17	17
DAB1/LIS1	-0.045	0.1	-9999	-0.48	6	6
DAB1/CRLK/C3G	-0.043	0.097	-9999	-0.46	6	6
PIK3CA	0.01	0	-9999	-10000	0	0
DAB1/NCK2	-0.046	0.1	-9999	-0.48	6	6
ARHGEF2	0.01	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.099	0.21	-9999	-0.51	73	73
CDK5R1	-0.005	0.088	-9999	-0.52	10	10
RELN	-0.062	0.18	-9999	-0.51	49	49
PIK3R1	0.01	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.048	0.11	-9999	-0.3	57	57
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.095	0.14	-9999	-0.52	14	14
MAPK8	0.01	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.048	0.11	-9999	-0.3	57	57
ITGB1	0.01	0	-9999	-10000	0	0
MAP1B	-0.028	0.12	-9999	-0.31	32	32
RELN/LRP8	-0.048	0.11	-9999	-0.3	57	57
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.05	0.11	-9999	-0.52	6	6
PI3K	0	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.003	0.033	-9999	-0.36	3	3
RAP1A	-0.004	0.11	-9999	-0.43	6	6
PAFAH1B1	0.01	0	-9999	-10000	0	0
MAPK8IP1	0.01	0	-9999	-10000	0	0
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.011	0.083	-9999	-0.52	9	9
NCK2	0.01	0	-9999	-10000	0	0
neuron differentiation	0.005	0.067	-9999	-10000	0	0
neuron adhesion	0.005	0.1	-9999	-0.4	7	7
LRP8	-0.002	0.079	-9999	-0.52	8	8
GSK3B	-0.004	0.09	-9999	-0.41	4	4
RELN/VLDLR/DAB1/Fyn	-0.044	0.1	-9999	-0.35	13	13
MAP3K11	0.008	0.027	-9999	-0.5	1	1
RELN/VLDLR/DAB1/P13K	-0.019	0.099	-9999	-0.25	49	49
CDK5	0.01	0	-9999	-10000	0	0
MAPT	-0.018	0.11	-9999	-0.47	19	19
neuron migration	-0.003	0.12	-9999	-0.46	4	4
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.004	0.068	-9999	-10000	0	0
RELN/VLDLR	-0.048	0.11	-9999	-0.28	61	61

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.14	0.23	-9999	-0.5	102	102
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.01	0	-9999	-10000	0	0
TCEB1	0.007	0.04	-9999	-0.52	2	2
HIF1A/p53	0.003	0.037	-9999	-10000	0	0
HIF1A	-0.003	0.038	-9999	-10000	0	0
COPS5	0.01	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.001	0.019	-9999	-10000	0	0
FIH (dimer)	0.01	0	-9999	-10000	0	0
CDKN2A	-0.15	0.24	-9999	-0.52	104	104
ARNT/IPAS	-0.1	0.16	-9999	-0.36	102	102
HIF1AN	0.01	0	-9999	-10000	0	0
GNB2L1	0.01	0	-9999	-10000	0	0
HIF1A/ARNT	0.003	0.037	-9999	-10000	0	0
CUL2	0.01	0	-9999	-10000	0	0
OS9	0.01	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.002	0.023	-9999	-0.31	2	2
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.003	0.037	-9999	-10000	0	0
PHD1-3/OS9	-0.077	0.12	-9999	-10000	0	0
HIF1A/RACK1/Elongin B/Elongin C	-0.013	0.026	-9999	-0.28	1	1
VHL	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
HIF1A/JAB1	0.003	0.037	-9999	-10000	0	0
EGLN3	-0.14	0.24	-9999	-0.52	99	99
EGLN2	0.01	0	-9999	-10000	0	0
EGLN1	0.01	0	-9999	-10000	0	0
TP53	0.01	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.021	0.014	-9999	-10000	0	0
ARNT	0.01	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.01	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.073	0.13	-9999	-0.31	36	36

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.008	0.093	-9999	-0.5	12	12
GNB1/GNG2	-0.051	0.1	-9999	-0.42	13	13
mol:DAG	-0.014	0.11	-9999	-0.39	13	13
PLCG1	-0.015	0.11	-9999	-0.4	13	13
YES1	-0.028	0.12	-9999	-0.44	13	13
FZD3	0.008	0.028	-9999	-0.52	1	1
FZD6	0.008	0.027	-9999	-0.5	1	1
G protein	-0.047	0.096	-9999	-0.4	13	13
MAP3K7	-0.022	0.13	-9999	-0.39	23	23
mol:Ca2+	-0.014	0.11	-9999	-0.38	13	13
mol:IP3	-0.014	0.11	-9999	-0.39	13	13
NLK	-0.003	0.007	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
CAMK2A	-0.03	0.14	-9999	-0.42	25	25
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.037	0.13	-9999	-0.48	13	13
CSNK1A1	0.01	0	-9999	-10000	0	0
GNAS	-0.028	0.12	-9999	-0.44	13	13
GO:0007205	-0.014	0.11	-9999	-0.38	13	13
WNT6	-0.023	0.13	-9999	-0.52	21	21
WNT4	-0.025	0.13	-9999	-0.51	24	24
NFAT1/CK1 alpha	-0.052	0.1	-9999	-0.43	13	13
GNG2	0.008	0.027	-9999	-0.5	1	1
WNT5A	0.004	0.054	-9999	-0.5	4	4
WNT11	-0.066	0.18	-9999	-0.5	52	52
CDC42	-0.02	0.12	-9999	-0.42	13	13

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.009	0.055	-9999	-0.48	4	4
Syndecan-4/Syndesmos	-0.02	0.087	-9999	-0.53	2	2
positive regulation of JNK cascade	-0.051	0.084	-9999	-0.45	4	4
Syndecan-4/ADAM12	-0.12	0.16	-9999	-0.38	60	60
CCL5	0.004	0.054	-9999	-0.5	4	4
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.01	0	-9999	-10000	0	0
ITGA5	0.008	0.028	-9999	-0.52	1	1
SDCBP	0.01	0	-9999	-10000	0	0
PLG	-0.009	0.08	-9999	-0.53	8	8
ADAM12	-0.19	0.26	-9999	-0.52	135	135
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.032	0.049	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.035	0.11	-9999	-0.42	10	10
Syndecan-4/CXCL12/CXCR4	-0.042	0.095	-9999	-0.47	4	4
Syndecan-4/Laminin alpha3	-0.068	0.13	-9999	-0.49	4	4
MDK	-0.17	0.25	-9999	-0.52	117	117
Syndecan-4/FZD7	-0.02	0.089	-9999	-0.47	3	3
Syndecan-4/Midkine	-0.1	0.15	-9999	-0.39	41	41
FZD7	0.008	0.027	-9999	-0.5	1	1
Syndecan-4/FGFR1/FGF	-0.065	0.11	-9999	-0.5	6	6
THBS1	0.007	0.039	-9999	-0.5	2	2
integrin-mediated signaling pathway	-0.04	0.11	-9999	-0.42	10	10
positive regulation of MAPKKK cascade	-0.051	0.084	-9999	-0.45	4	4
Syndecan-4/TACI	-0.04	0.12	-9999	-0.4	15	15
CXCR4	0.01	0	-9999	-10000	0	0
cell adhesion	0.004	0.036	-9999	-0.24	6	6
Syndecan-4/Dynamin	-0.02	0.087	-9999	-0.53	2	2
Syndecan-4/TSP1	-0.021	0.093	-9999	-0.64	2	2
Syndecan-4/GIPC	-0.02	0.087	-9999	-0.53	2	2
Syndecan-4/RANTES	-0.022	0.09	-9999	-0.53	2	2
ITGB1	0.01	0	-9999	-10000	0	0
LAMA1	-0.023	0.13	-9999	-0.52	22	22
LAMA3	-0.092	0.2	-9999	-0.5	70	70
RAC1	0.01	0	-9999	-10000	0	0
PRKCA	0.014	0.044	-9999	-0.46	2	2
Syndecan-4/alpha-Actinin	-0.02	0.087	-9999	-0.53	2	2
TFPI	-0.008	0.093	-9999	-0.5	12	12
F2	-0.07	0.18	-9999	-0.52	49	49
alpha5/beta1 Integrin	-0.001	0.02	-9999	-0.37	1	1
positive regulation of cell adhesion	-0.076	0.14	-9999	-0.49	7	7
ACTN1	0.01	0	-9999	-10000	0	0
TNC	-0.035	0.15	-9999	-0.52	30	30
Syndecan-4/CXCL12	-0.035	0.11	-9999	-0.42	9	9
FGF6	0	0.001	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
CXCL12	-0.022	0.12	-9999	-0.5	22	22
TNFRSF13B	-0.032	0.14	-9999	-0.52	28	28
FGF2	-0.051	0.17	-9999	-0.5	42	42
FGFR1	0.005	0.048	-9999	-0.51	3	3
Syndecan-4/PI-4-5-P2	-0.026	0.087	-9999	-0.54	2	2
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.006	0.053	-9999	-0.49	4	4
cell migration	-0.013	0.021	-9999	-10000	0	0
PRKCD	0.011	0.006	-9999	-10000	0	0
vasculogenesis	-0.02	0.09	-9999	-0.61	2	2
SDC4	-0.027	0.092	-9999	-0.57	2	2
Syndecan-4/Tenascin C	-0.041	0.11	-9999	-0.43	10	10
Syndecan-4/PI-4-5-P2/PKC alpha	-0.026	0.039	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.02	0.087	-9999	-0.53	2	2
MMP9	-0.081	0.2	-9999	-0.52	60	60
Rac1/GTP	0.004	0.036	-9999	-0.25	6	6
cytoskeleton organization	-0.019	0.085	-9999	-0.51	2	2
GIPC1	0.01	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.028	0.1	-9999	-0.64	2	2

×

Coregulation of Androgen receptor activity

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	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.01	0.001	-9999	-10000	0	0
SVIL	0.01	0.001	-9999	-10000	0	0
ZNF318	0.009	0.007	-9999	-10000	0	0
JMJD2C	-0.001	0.018	-9999	-0.08	16	16
T-DHT/AR/Ubc9	-0.048	0.1	-9999	-0.33	40	40
CARM1	0.01	0	-9999	-10000	0	0
PRDX1	0.008	0.028	-9999	-0.52	1	1
PELP1	0.01	0.001	-9999	-10000	0	0
CTNNB1	0.01	0.001	-9999	-10000	0	0
AKT1	0.01	0.002	-9999	-10000	0	0
PTK2B	0.007	0.039	-9999	-0.5	2	2
MED1	0.01	0.002	-9999	-10000	0	0
MAK	-0.007	0.09	-9999	-0.51	11	11
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.004	0.054	-9999	-0.5	4	4
GSN	0.01	0.001	-9999	-10000	0	0
NCOA2	0.007	0.039	-9999	-0.5	2	2
NCOA6	0.01	0.001	-9999	-10000	0	0
DNA-PK	0.001	0.009	-9999	-10000	0	0
NCOA4	0.01	0	-9999	-10000	0	0
PIAS3	0.01	0.001	-9999	-10000	0	0
cell proliferation	-0.032	0.12	-9999	-0.72	10	10
XRCC5	0.01	0.001	-9999	-10000	0	0
UBE3A	0.01	0.003	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.057	0.12	-9999	-0.33	49	49
FHL2	-0.069	0.13	-9999	-0.36	54	54
RANBP9	0.01	0.001	-9999	-10000	0	0
JMJD1A	-0.001	0.042	-9999	-0.13	35	35
CDK6	0.007	0.039	-9999	-0.51	2	2
TGFB1I1	0.007	0.039	-9999	-0.5	2	2
T-DHT/AR/CyclinD1	-0.049	0.11	-9999	-0.33	43	43
XRCC6	0.01	0.001	-9999	-10000	0	0
T-DHT/AR	-0.037	0.14	-9999	-0.34	47	47
CTDSP1	0.01	0.001	-9999	-10000	0	0
CTDSP2	0.01	0.004	-9999	-10000	0	0
BRCA1	0.008	0.028	-9999	-0.52	1	1
TCF4	0.007	0.039	-9999	-0.5	2	2
CDKN2A	-0.15	0.24	-9999	-0.52	104	104
SRF	0.004	0.029	-9999	-10000	0	0
NKX3-1	-0.045	0.12	-9999	-0.94	4	4
KLK3	0.016	0.047	-9999	-10000	0	0
TMF1	0.01	0.001	-9999	-10000	0	0
HNRNPA1	0.01	0.002	-9999	-10000	0	0
AOF2	0	0.003	-9999	-10000	0	0
APPL1	0.018	0.004	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.048	0.1	-9999	-0.33	40	40
AR	-0.057	0.17	-9999	-0.52	40	40
UBA3	0.01	0.001	-9999	-10000	0	0
PATZ1	0.01	0.002	-9999	-10000	0	0
PAWR	0.01	0.001	-9999	-10000	0	0
PRKDC	0.01	0.001	-9999	-10000	0	0
PA2G4	0.01	0.003	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.029	0.1	-9999	-0.3	40	40
RPS6KA3	0.01	0.001	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.046	0.11	-9999	-0.33	40	40
LATS2	0.01	0.002	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.031	0.11	-9999	-0.31	40	40
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	0.004	0.055	-9999	-0.51	4	4
KLK2	-0.039	0.087	-9999	-0.38	16	16
CASP8	0.01	0.001	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.041	0.097	-9999	-0.29	42	42
TMPRSS2	-0.1	0.28	-9999	-0.98	32	32
CCND1	0.005	0.047	-9999	-0.5	3	3
PIAS1	0.01	0.003	-9999	-10000	0	0
mol:T-DHT	-0.009	0.028	-9999	-0.08	27	27
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.01	0.005	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.05	0.11	-9999	-0.33	42	42
CMTM2	-0.089	0.2	-9999	-0.5	68	68
SNURF	-0.005	0.085	-9999	-0.5	10	10
ZMIZ1	0.003	0.024	-9999	-10000	0	0
CCND3	0.01	0	-9999	-10000	0	0
TGIF1	0.01	0.002	-9999	-10000	0	0
FKBP4	0.008	0.028	-9999	-0.52	1	1

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	0.016	0.1	-10000	0	-0.41	18	18
CRKL	0.014	0.1	-10000	0	-0.43	17	17
HRAS	0.026	0.11	-10000	0	-0.39	19	19
mol:PIP3	0.002	0.097	-10000	0	-0.41	17	17
SPRED1	0.01	0	-10000	0	-10000	0	0
SPRED2	0.01	0	-10000	0	-10000	0	0
GAB1	0.007	0.11	-10000	0	-0.45	17	17
FOXO3	0.018	0.094	-10000	0	-0.39	17	17
AKT1	0.012	0.1	-10000	0	-0.42	17	17
BAD	0.018	0.094	-10000	0	-0.39	17	17
megakaryocyte differentiation	-0.015	0.14	-10000	0	-0.49	20	20
GSK3B	0.018	0.094	-10000	0	-0.39	17	17
RAF1	0.032	0.089	-10000	0	-0.39	8	8
SHC1	0.01	0	-10000	0	-10000	0	0
STAT3	0.008	0.11	-10000	0	-0.45	17	17
STAT1	0.003	0.22	-10000	0	-0.98	17	17
HRAS/SPRED1	-0.021	0.074	-10000	0	-0.39	8	8
cell proliferation	0.009	0.11	-10000	0	-0.44	17	17
PIK3CA	0.01	0	-10000	0	-10000	0	0
TEC	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.008	0.11	-10000	0	-0.46	17	17
HRAS/SPRED2	-0.021	0.074	-10000	0	-0.39	8	8
LYN/TEC/p62DOK	-0.022	0.092	-10000	0	-0.42	17	17
MAPK3	0.037	0.067	-10000	0	-0.28	7	7
STAP1	0.002	0.12	-10000	0	-0.45	18	18
GRAP2	-0.005	0.085	-10000	0	-0.5	10	10
JAK2	-0.044	0.18	-10000	0	-0.84	17	17
STAT1 (dimer)	0.004	0.22	-10000	0	-0.95	17	17
mol:Gleevec	-0.002	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.025	0.096	-10000	0	-0.42	18	18
actin filament polymerization	0.008	0.11	-10000	0	-0.44	17	17
LYN	0.01	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	0.009	0.15	-10000	0	-0.6	18	18
PIK3R1	0.01	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.02	0.084	-10000	0	-0.38	17	17
PI3K	-0.022	0.095	-10000	0	-0.43	17	17
PTEN	0.01	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.002	0.27	-10000	0	-1.2	17	17
MAPK8	0.008	0.11	-10000	0	-0.45	17	17
STAT3 (dimer)	0.009	0.11	-10000	0	-0.44	17	17
positive regulation of transcription	0.035	0.056	-10000	0	-0.22	7	7
mol:GDP	-0.027	0.097	-10000	0	-0.4	19	19
PIK3C2B	0.008	0.11	-10000	0	-0.45	17	17
CBL/CRKL	0.019	0.098	-10000	0	-0.4	17	17
FER	0.008	0.11	-10000	0	-0.45	17	17
SH2B3	0.007	0.11	-10000	0	-0.45	18	18
PDPK1	0.008	0.09	-10000	0	-0.37	17	17
SNAI2	0.005	0.12	-10000	0	-0.48	18	18
positive regulation of cell proliferation	0.009	0.17	-10000	0	-0.74	17	17
KITLG	0.007	0.058	-10000	0	-0.53	4	4
cell motility	0.009	0.17	-10000	0	-0.74	17	17
PTPN6	0.002	0.007	-10000	0	-10000	0	0
EPOR	0.029	0.067	-10000	0	-10000	0	0
STAT5A (dimer)	0.011	0.15	-10000	0	-0.62	17	17
SOCS1	0.01	0	-10000	0	-10000	0	0
cell migration	0.005	0.12	0.46	17	-10000	0	17
SOS1	0.01	0	-10000	0	-10000	0	0
EPO	0.005	0.041	-10000	0	-0.53	2	2
VAV1	0.002	0.061	-10000	0	-0.5	5	5
GRB10	0.008	0.11	-10000	0	-0.45	17	17
PTPN11	0.001	0.006	-10000	0	-10000	0	0
SCF/KIT	-0.015	0.11	-10000	0	-0.47	18	18
GO:0007205	-0.001	0.005	-10000	0	-10000	0	0
MAP2K1	0.036	0.072	-10000	0	-0.3	7	7
CBL	0.01	0	-10000	0	-10000	0	0
KIT	-0.018	0.27	-10000	0	-1.2	17	17
MAP2K2	0.036	0.072	-10000	0	-0.3	7	7
SHC/Grb2/SOS1	-0.022	0.092	-10000	0	-0.42	17	17
STAT5A	0.011	0.15	-10000	0	-0.64	17	17
GRB2	0.01	0	-10000	0	-10000	0	0
response to radiation	0.005	0.12	-10000	0	-0.47	18	18
SHC/GRAP2	-0.01	0.059	-10000	0	-0.36	10	10
PTPRO	-0.016	0.14	-10000	0	-0.5	20	20
SH2B2	0.008	0.11	-10000	0	-0.45	17	17
DOK1	0.01	0	-10000	0	-10000	0	0
MATK	-0.006	0.12	-10000	0	-0.47	17	17
CREBBP	0.029	0.007	-10000	0	-10000	0	0
BCL2	0.028	0.07	-10000	0	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.024	0.095	-10000	0	-0.37	8	8
TBX21	-0.006	0.34	-10000	0	-1.2	22	22
B2M	0.011	0.003	-10000	0	-10000	0	0
TYK2	0.018	0.014	-10000	0	-10000	0	0
IL12RB1	0.001	0.095	-10000	0	-0.52	11	11
GADD45B	0.018	0.27	-10000	0	-1	15	15
IL12RB2	-0.031	0.16	-10000	0	-0.51	33	33
GADD45G	0.017	0.27	-10000	0	-0.95	18	18
natural killer cell activation	0.008	0.016	-10000	0	-10000	0	0
RELB	0.01	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
IL18	0.002	0.078	-10000	0	-0.51	8	8
IL2RA	-0.035	0.15	-10000	0	-0.52	30	30
IFNG	-0.039	0.15	-10000	0	-0.52	32	32
STAT3 (dimer)	0.027	0.23	-10000	0	-0.77	17	17
HLA-DRB5	-0.04	0.15	-10000	0	-0.5	34	34
FASLG	0.015	0.29	-10000	0	-1.1	16	16
NF kappa B2 p52/RelB	-0.08	0.22	-10000	0	-0.91	17	17
CD4	0.001	0.067	-10000	0	-0.5	6	6
SOCS1	0.01	0	-10000	0	-10000	0	0
EntrezGene:6955	0	0.008	-10000	0	-10000	0	0
CD3D	0.008	0.04	-10000	0	-0.51	2	2
CD3E	0.008	0.039	-10000	0	-0.5	2	2
CD3G	0.004	0.061	-10000	0	-0.5	5	5
IL12Rbeta2/JAK2	-0.007	0.12	-10000	0	-0.36	33	33
CCL3	0.017	0.28	-10000	0	-0.98	17	17
CCL4	0.018	0.28	-10000	0	-1	16	16
HLA-A	0.011	0.003	-10000	0	-10000	0	0
IL18/IL18R	0.016	0.13	-10000	0	-0.36	31	31
NOS2	-0.035	0.4	-10000	0	-1.2	35	35
IL12/IL12R/TYK2/JAK2/SPHK2	0.023	0.096	-10000	0	-0.39	7	7
IL1R1	0.019	0.28	-10000	0	-1	15	15
IL4	-0.004	0.016	-10000	0	-10000	0	0
JAK2	0.018	0.014	-10000	0	-10000	0	0
EntrezGene:6957	0	0.007	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.017	0.17	-10000	0	-1.2	5	5
RAB7A	0.038	0.23	-10000	0	-0.81	12	12
lysosomal transport	0.04	0.22	-10000	0	-0.76	12	12
FOS	-0.054	0.36	-10000	0	-1.1	34	34
STAT4 (dimer)	0.036	0.26	-10000	0	-0.9	16	16
STAT5A (dimer)	-0.096	0.23	-10000	0	-0.85	22	22
GZMA	0.019	0.27	-10000	0	-1	15	15
GZMB	0.006	0.31	-10000	0	-1.1	18	18
HLX	0.002	0.061	-10000	0	-0.51	5	5
LCK	0.018	0.29	-10000	0	-1	17	17
TCR/CD3/MHC II/CD4	-0.018	0.15	-10000	0	-0.53	18	18
IL2/IL2R	-0.028	0.089	-10000	0	-0.29	34	34
MAPK14	0.024	0.27	-10000	0	-0.9	18	18
CCR5	0.019	0.26	-10000	0	-0.97	15	15
IL1B	-0.012	0.12	-10000	0	-0.51	20	20
STAT6	0.03	0.084	-10000	0	-0.26	2	2
STAT4	0.01	0	-10000	0	-10000	0	0
STAT3	0.01	0	-10000	0	-10000	0	0
STAT1	0.01	0	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
NFKB2	0.01	0	-10000	0	-10000	0	0
IL12B	0.013	0.059	-10000	0	-0.53	4	4
CD8A	0.005	0.056	-10000	0	-0.51	4	4
CD8B	0.001	0.073	-10000	0	-0.51	7	7
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.024	0.095	0.37	8	-10000	0	8
IL2RB	0.007	0.039	-10000	0	-0.5	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.04	0.24	-10000	0	-0.8	16	16
IL2RG	0.004	0.054	-10000	0	-0.5	4	4
IL12	0.02	0.068	-10000	0	-0.37	9	9
STAT5A	0.008	0.027	-10000	0	-0.5	1	1
CD247	0.005	0.055	-10000	0	-0.51	4	4
IL2	0.006	0.005	-10000	0	-10000	0	0
SPHK2	0.008	0.027	-10000	0	-0.5	1	1
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.01	0.065	-10000	0	-0.52	5	5
IL12/IL12R/TYK2/JAK2	0.013	0.31	-10000	0	-1.1	18	18
MAP2K3	0.021	0.28	-10000	0	-0.92	18	18
RIPK2	0.01	0	-10000	0	-10000	0	0
MAP2K6	0.02	0.28	-10000	0	-0.9	19	19
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.009	0.097	-10000	0	-0.5	13	13
IL18RAP	-0.009	0.11	-10000	0	-0.51	16	16
IL12Rbeta1/TYK2	0.013	0.074	-10000	0	-0.38	11	11
EOMES	-0.003	0.12	-10000	0	-1.2	3	3
STAT1 (dimer)	0.022	0.23	-10000	0	-0.76	17	17
T cell proliferation	0.032	0.21	-10000	0	-0.65	17	17
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.006	0.1	-10000	0	-0.51	14	14
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.075	0.18	-10000	0	-0.7	19	19
ATF2	0.032	0.25	-10000	0	-0.85	16	16

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.008	0.027	-9999	-0.5	1	1
alphaV beta3 Integrin	-0.024	0.091	-9999	-0.37	23	23
PTK2	-0.032	0.1	-9999	-0.42	19	19
positive regulation of JNK cascade	-0.017	0.066	-9999	-0.29	19	19
CDC42/GDP	0.018	0.1	-9999	-0.39	19	19
Rac1/GDP	0.02	0.099	-9999	-0.39	19	19
RAP1B	0.01	0	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
CTNNB1	0.01	0	-9999	-10000	0	0
CDC42/GTP	-0.02	0.081	-9999	-0.36	19	19
nectin-3/I-afadin	-0.02	0.082	-9999	-0.36	20	20
RAPGEF1	0.014	0.11	-9999	-0.43	19	19
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.006	0.12	-9999	-0.5	19	19
PDGFB-D/PDGFRB	0.008	0.027	-9999	-0.5	1	1
TLN1	0.008	0.085	-9999	-0.45	9	9
Rap1/GTP	-0.017	0.07	-9999	-0.31	19	19
IQGAP1	0.01	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	-0.02	0.082	-9999	-0.36	20	20
PVR	0.01	0	-9999	-10000	0	0
Necl-5(dimer)	0.01	0	-9999	-10000	0	0
mol:GDP	0.014	0.12	-9999	-0.48	19	19
MLLT4	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	-0.014	0.059	-9999	-0.49	1	1
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.011	0.062	-9999	-0.37	10	10
positive regulation of lamellipodium assembly	-0.018	0.071	-9999	-0.3	20	20
PVRL1	-0.005	0.088	-9999	-0.52	10	10
PVRL3	-0.019	0.12	-9999	-0.5	20	20
PVRL2	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
CDH1	0.007	0.039	-9999	-0.5	2	2
CLDN1	-0.008	0.096	-9999	-0.52	12	12
JAM-A/CLDN1	-0.025	0.084	-9999	-0.29	30	30
SRC	-0.033	0.13	-9999	-0.55	19	19
ITGB3	-0.025	0.13	-9999	-0.52	23	23
nectin-1(dimer)/I-afadin/I-afadin	-0.011	0.062	-9999	-0.37	10	10
FARP2	0.01	0.12	-9999	-0.47	19	19
RAC1	0.01	0	-9999	-10000	0	0
CTNNA1	0.01	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.017	0.068	-9999	-0.3	20	20
nectin-1/I-afadin	-0.011	0.062	-9999	-0.37	10	10
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	-0.025	0.086	-9999	-0.31	29	29
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.008	0.027	-9999	-0.5	1	1
positive regulation of filopodium formation	-0.017	0.066	-9999	-0.29	19	19
alphaV/beta3 Integrin/Talin	-0.03	0.09	-9999	-0.42	10	10
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	0.002	0.089	-9999	-0.51	8	8
VAV2	0.008	0.12	-9999	-0.48	20	20
RAP1/GDP	-0.02	0.082	-9999	-0.36	19	19
ITGAV	0.01	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.017	0.068	-9999	-0.3	20	20
nectin-3(dimer)/I-afadin/I-afadin	-0.02	0.082	-9999	-0.36	20	20
Rac1/GTP	-0.022	0.086	-9999	-0.37	20	20
PTPRM	-0.021	0.093	-9999	-0.32	22	22
E-cadherin/beta catenin/alpha catenin	-0.008	0.042	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.008	0.04	-9999	-0.32	3	3
NFATC2	0	0.066	-9999	-0.32	12	12
NFATC3	0.011	0.026	-9999	-10000	0	0
CD40LG	-0.04	0.22	-9999	-0.59	28	28
PTGS2	-0.052	0.24	-9999	-0.61	31	31
JUNB	0.007	0.039	-9999	-0.5	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.006	0.01	-9999	-10000	0	0
CaM/Ca2+	-0.006	0.009	-9999	-10000	0	0
CALM1	0.009	0.007	-9999	-10000	0	0
JUN	0.006	0.039	-9999	-0.5	2	2
mol:Ca2+	-0.005	0.01	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.002	-9999	-10000	0	0
FOSL1	-0.028	0.14	-9999	-0.52	25	25
CREM	0.009	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.049	0.093	-9999	-0.45	9	9
FOS	-0.031	0.14	-9999	-0.51	27	27
IFNG	-0.048	0.23	-9999	-0.62	30	30
AP-1/NFAT1-c-4	-0.11	0.18	-9999	-0.56	37	37
FASLG	-0.03	0.2	-9999	-0.62	17	17
NFAT1-c-4/ICER1	-0.031	0.07	-9999	-0.4	7	7
IL2RA	-0.046	0.22	-9999	-0.59	30	30
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.046	0.23	-9999	-0.58	34	34
JunB/Fra1/NFAT1-c-4	-0.046	0.094	-9999	-0.37	18	18
IL4	-0.032	0.2	-9999	-0.58	17	17
IL2	-0.002	0.01	-9999	-10000	0	0
IL3	-0.01	0.016	-9999	-10000	0	0
FKBP1A	0.01	0	-9999	-10000	0	0
BATF3	0.008	0.028	-9999	-0.52	1	1
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.01	0.001	-9999	-10000	0	0

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.012	0.065	-9999	-0.34	13	13
EFNA5	0.001	0.068	-9999	-0.51	6	6
FYN	0.006	0.061	-9999	-0.3	13	13
neuron projection morphogenesis	-0.012	0.065	-9999	-0.34	13	13
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.012	0.065	-9999	-0.34	13	13
EPHA5	-0.006	0.079	-9999	-0.52	8	8

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.008	0.027	-10000	0	-0.5	1	1
Jak2/Leptin Receptor	-0.024	0.069	-10000	0	-0.34	7	7
PTP1B/AKT1	0.009	0.039	-10000	0	-0.22	1	1
FYN	0.01	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0.004	0.043	-10000	0	-0.23	2	2
EGFR	-0.006	0.087	-10000	0	-0.52	10	10
EGF/EGFR	-0.05	0.09	-10000	0	-0.28	15	15
CSF1	0.005	0.047	-10000	0	-0.5	3	3
AKT1	0.01	0.001	-10000	0	-10000	0	0
INSR	0.01	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.021	0.092	-10000	0	-0.26	40	40
Insulin Receptor/Insulin	-0.007	0.023	-10000	0	-10000	0	0
HCK	-0.011	0.1	-10000	0	-0.5	14	14
CRK	0.01	0	-10000	0	-10000	0	0
TYK2	0.01	0.041	-10000	0	-0.24	1	1
EGF	-0.09	0.21	-10000	0	-0.52	67	67
YES1	0.01	0	-10000	0	-10000	0	0
CAV1	-0.089	0.096	-10000	0	-0.25	49	49
TXN	0.005	0.04	-10000	0	-0.52	2	2
PTP1B/IRS1/GRB2	-0.008	0.031	-10000	0	-0.26	2	2
cell migration	-0.004	0.043	0.23	2	-10000	0	2
STAT3	0.01	0.001	-10000	0	-10000	0	0
PRLR	-0.053	0.17	-10000	0	-0.52	42	42
ITGA2B	-0.043	0.16	-10000	0	-0.51	36	36
CSF1R	0.001	0.066	-10000	0	-0.5	6	6
Prolactin Receptor/Prolactin	-0.055	0.14	-10000	0	-0.38	51	51
FGR	-0.037	0.15	-10000	0	-0.5	32	32
PTP1B/p130 Cas	0.009	0.043	-10000	0	-0.26	2	2
Crk/p130 Cas	-0.008	0.03	-10000	0	-0.26	1	1
DOK1	0.015	0.04	-10000	0	-0.25	1	1
JAK2	-0.003	0.054	-10000	0	-0.29	5	5
Jak2/Leptin Receptor/Leptin	-0.027	0.061	-10000	0	-0.36	2	2
PIK3R1	0.01	0	-10000	0	-10000	0	0
PTPN1	0.004	0.043	-10000	0	-0.23	2	2
LYN	0.01	0	-10000	0	-10000	0	0
CDH2	-0.049	0.17	-10000	0	-0.52	39	39
SRC	0.014	0.018	-10000	0	-10000	0	0
ITGB3	-0.026	0.13	-10000	0	-0.52	23	23
CAT1/PTP1B	-0.031	0.13	-10000	0	-0.48	17	17
CAPN1	0.01	0.001	-10000	0	-10000	0	0
CSK	0.01	0	-10000	0	-10000	0	0
PI3K	-0.003	0.019	-10000	0	-10000	0	0
mol:H2O2	-0.001	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	-0.022	0.059	-10000	0	-0.39	2	2
negative regulation of transcription	-0.002	0.054	-10000	0	-0.28	5	5
FCGR2A	0.002	0.061	-10000	0	-0.5	5	5
FER	0.008	0.004	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.06	0.14	-10000	0	-0.37	58	58
BLK	-0.054	0.17	-10000	0	-0.52	42	42
Insulin Receptor/Insulin/Shc	0	0	-10000	0	-10000	0	0
RHOA	0.01	0.001	-10000	0	-10000	0	0
LEPR	-0.017	0.11	-10000	0	-0.5	18	18
BCAR1	0.008	0.027	-10000	0	-0.5	1	1
p210 bcr-abl/Grb2	0.01	0	-10000	0	-10000	0	0
mol:NADPH	0	0.002	-10000	0	-10000	0	0
TRPV6	-0.037	0.14	-10000	0	-0.52	17	17
PRL	-0.012	0.087	-10000	0	-0.52	10	10
SOCS3	0.003	0.094	-10000	0	-1.2	2	2
SPRY2	0.006	0.028	-10000	0	-0.51	1	1
Insulin Receptor/Insulin/IRS1	-0.001	0.016	-10000	0	-0.31	1	1
CSF1/CSF1R	-0.013	0.057	-10000	0	-0.38	5	5
Ras protein signal transduction	0.011	0.015	-10000	0	-10000	0	0
IRS1	0.008	0.027	-10000	0	-0.5	1	1
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.05	0.17	-10000	0	-0.52	39	39
STAT5B	0.003	0.043	-10000	0	-0.23	2	2
STAT5A	0.003	0.044	-10000	0	-0.23	3	3
GRB2	0.01	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.009	0.043	-10000	0	-0.26	2	2
CSN2	-0.014	0.044	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
LAT	0.007	0.059	-10000	0	-0.46	5	5
YBX1	0.016	0.001	-10000	0	-10000	0	0
LCK	0.007	0.039	-10000	0	-0.51	2	2
SHC1	0.01	0	-10000	0	-10000	0	0
NOX4	-0.016	0.11	-10000	0	-0.52	16	16

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.01	0	-10000	0	-10000	0	0
HDAC4	0.008	0.028	-10000	0	-0.52	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.012	0.1	0.37	26	-10000	0	26
CDKN1A	-0.002	0.036	-10000	0	-0.68	1	1
KAT2B	0.01	0	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
FOXO1	0.01	0	-10000	0	-10000	0	0
FOXO4	0.018	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.01	0	-10000	0	-10000	0	0
TAT	-0.031	0.14	-10000	0	-0.52	27	27
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.008	0.029	-10000	0	-0.37	2	2
PPARGC1A	-0.11	0.22	-10000	0	-0.5	83	83
FHL2	-0.072	0.19	-10000	0	-0.52	54	54
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.007	-10000	0	-10000	0	0
HIST2H4A	-0.012	0.1	-10000	0	-0.37	26	26
SIRT1/FOXO3a	0	0.007	-10000	0	-10000	0	0
SIRT1	0.001	0.01	0.19	1	-10000	0	1
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	-0.001	0.018	-10000	0	-0.31	1	1
SIRT1/Histone H1b	-0.009	0.032	-10000	0	-10000	0	0
apoptosis	0	0.007	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.071	0.13	-10000	0	-0.3	83	83
p53/SIRT1	0.001	0.02	0.38	1	-10000	0	1
SIRT1/FOXO4	0	0.008	0.15	1	-10000	0	1
FOXO1/FHL2/SIRT1	-0.043	0.1	-10000	0	-0.28	54	54
HIST1H1E	0.005	0.044	-10000	0	-10000	0	0
SIRT1/p300	0	0.007	-10000	0	-10000	0	0
muscle cell differentiation	0.001	0.024	0.31	2	-10000	0	2
TP53	0.001	0.01	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.007	-10000	0	-10000	0	0
CREBBP	0.01	0	-10000	0	-10000	0	0
MEF2D	0.01	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.028	0.099	-10000	0	-0.37	27	27
ACSS2	0.015	0.021	-10000	0	-0.36	1	1
SIRT1/PCAF/MYOD	-0.001	0.024	-10000	0	-0.31	2	2

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.001	0.013	-10000	0	-10000	0	0
RFC1	0.001	0.013	-10000	0	-10000	0	0
PRKDC	0.001	0.013	-10000	0	-10000	0	0
RIPK1	0.011	0.004	-10000	0	-10000	0	0
CASP7	-0.014	0.031	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	0.006	0.075	0.2	27	-0.26	7	34
MAP2K4	-0.02	0.13	-10000	0	-0.44	6	6
mol:ceramide	-0.006	0.09	-10000	0	-0.36	8	8
GSN	0.001	0.013	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	0.014	0.077	0.18	27	-0.32	6	33
FAS	0.004	0.048	-10000	0	-0.51	3	3
BID	0.001	0.008	-10000	0	-10000	0	0
MAP3K1	-0.003	0.077	-10000	0	-0.25	4	4
MAP3K7	0.008	0.004	-10000	0	-10000	0	0
RB1	0.001	0.013	-10000	0	-10000	0	0
CFLAR	0.011	0.004	-10000	0	-10000	0	0
HGF/MET	-0.065	0.15	-10000	0	-0.35	66	66
ARHGDIB	0.001	0.013	-10000	0	-10000	0	0
FADD	0.008	0.004	-10000	0	-10000	0	0
actin filament polymerization	-0.001	0.013	-10000	0	-10000	0	0
NFKB1	-0.044	0.083	-10000	0	-0.26	6	6
MAPK8	-0.048	0.2	-10000	0	-0.42	76	76
DFFA	0.001	0.013	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.001	0.013	-10000	0	-10000	0	0
FAS/FADD/MET	-0.022	0.079	-10000	0	-0.3	26	26
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	0.008	0.04	-10000	0	-0.52	2	2
FAF1	0.009	0.005	-10000	0	-10000	0	0
PARP1	0.001	0.013	-10000	0	-10000	0	0
DFFB	0.001	0.013	-10000	0	-10000	0	0
CHUK	-0.039	0.073	-10000	0	-10000	0	0
FASLG	0.001	0.062	-10000	0	-0.51	5	5
FAS/FADD	-0.005	0.034	-10000	0	-0.37	3	3
HGF	-0.017	0.11	-10000	0	-0.51	18	18
LMNA	0.001	0.012	-10000	0	-10000	0	0
CASP6	0.001	0.013	-10000	0	-10000	0	0
CASP10	0.007	0.028	-10000	0	-0.52	1	1
CASP3	0.002	0.016	0.2	2	-10000	0	2
PTPN13	-0.044	0.16	-10000	0	-0.5	37	37
CASP8	0.001	0.016	0.21	2	-10000	0	2
IL6	-0.23	0.5	-10000	0	-1.2	76	76
MET	-0.024	0.13	-10000	0	-0.51	23	23
ICAD/CAD	0.001	0.013	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.006	0.09	-10000	0	-0.37	8	8
activation of caspase activity by cytochrome c	0.001	0.008	-10000	0	-10000	0	0
PAK2	0.001	0.013	-10000	0	-10000	0	0
BCL2	0.007	0.04	-10000	0	-0.52	2	2

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.01	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.03	0.074	-9999	-10000	0	0
Syndecan-3/Neurocan	-0.006	0.039	-9999	-0.32	1	1
POMC	-0.017	0.11	-9999	-0.51	18	18
EGFR	-0.005	0.087	-9999	-0.52	10	10
Syndecan-3/EGFR	-0.007	0.041	-9999	-10000	0	0
AGRP	-0.2	0.25	-9999	-0.5	140	140
NCSTN	0.01	0	-9999	-10000	0	0
PSENEN	0.008	0.028	-9999	-0.52	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.008	0.027	-9999	-0.5	1	1
APH1A	0.01	0	-9999	-10000	0	0
NCAN	-0.005	0.079	-9999	-0.52	8	8
long-term memory	0	0.003	-9999	-10000	0	0
Syndecan-3/IL8	-0.014	0.057	-9999	-10000	0	0
PSEN1	0.01	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	0.01	0	-9999	-10000	0	0
limb bud formation	0	0.004	-9999	-10000	0	0
MC4R	-0.035	0.14	-9999	-0.52	28	28
SRC	0.01	0	-9999	-10000	0	0
PTN	-0.062	0.18	-9999	-0.5	49	49
FGFR/FGF/Syndecan-3	0	0.004	-9999	-10000	0	0
neuron projection morphogenesis	-0.034	0.078	-9999	-0.44	1	1
Syndecan-3/AgRP	-0.096	0.12	-9999	-0.3	2	2
Syndecan-3/AgRP/MC4R	-0.11	0.13	-9999	-0.45	13	13
Fyn/Cortactin	0	0	-9999	-10000	0	0
SDC3	0	0.004	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.014	0.056	-9999	-10000	0	0
IL8	-0.019	0.12	-9999	-0.52	19	19
Syndecan-3/Fyn/Cortactin	0	0.003	-9999	-10000	0	0
Syndecan-3/CASK	0	0.004	-9999	-10000	0	0
alpha-MSH/MC4R	-0.047	0.13	-9999	-0.39	43	43
Gamma Secretase	-0.001	0.018	-9999	-10000	0	0

×

EPHB forward 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.045	0.12	-10000	0	-0.33	49	49
cell-cell adhesion	0.051	0.097	0.42	8	-10000	0	8
Ephrin B/EPHB2/RasGAP	-0.037	0.088	-10000	0	-10000	0	0
ITSN1	0.01	0	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
SHC1	0.01	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.009	0.052	-10000	0	-0.31	10	10
Ephrin B1/EPHB1	-0.037	0.1	-10000	0	-0.31	41	41
HRAS/GDP	-0.033	0.075	-10000	0	-0.29	7	7
Ephrin B/EPHB1/GRB7	-0.037	0.093	-10000	0	-0.52	2	2
Endophilin/SYNJ1	-0.009	0.093	-10000	0	-10000	0	0
KRAS	0.01	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.033	0.085	-10000	0	-10000	0	0
endothelial cell migration	-0.002	0.022	-10000	0	-0.24	3	3
GRB2	0.01	0	-10000	0	-10000	0	0
GRB7	0.002	0.062	-10000	0	-0.52	5	5
PAK1	-0.005	0.098	-10000	0	-0.46	1	1
HRAS	0.01	0	-10000	0	-10000	0	0
RRAS	-0.011	0.1	-10000	0	-0.48	2	2
DNM1	0.004	0.056	-10000	0	-0.52	4	4
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.005	0.091	-10000	0	-10000	0	0
lamellipodium assembly	-0.051	0.097	-10000	0	-0.42	8	8
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.01	0.056	-10000	0	-0.22	4	4
PIK3R1	0.01	0	-10000	0	-10000	0	0
EPHB2	-0.058	0.18	-10000	0	-0.52	45	45
EPHB3	-0.004	0.084	-10000	0	-0.52	9	9
EPHB1	-0.051	0.17	-10000	0	-0.52	40	40
EPHB4	0.01	0	-10000	0	-10000	0	0
mol:GDP	-0.029	0.073	-10000	0	-0.27	10	10
Ephrin B/EPHB2	-0.038	0.091	-10000	0	-0.26	52	52
Ephrin B/EPHB3	-0.011	0.053	-10000	0	-0.25	16	16
JNK cascade	-0.036	0.13	-10000	0	-0.51	8	8
Ephrin B/EPHB1	-0.034	0.087	-10000	0	-0.26	47	47
RAP1/GDP	-0.024	0.063	-10000	0	-10000	0	0
EFNB2	0.005	0.047	-10000	0	-0.5	3	3
EFNB3	0.005	0.048	-10000	0	-0.52	3	3
EFNB1	0.008	0.027	-10000	0	-0.5	1	1
Ephrin B2/EPHB1-2	-0.069	0.13	-10000	0	-0.31	80	80
RAP1B	0.01	0	-10000	0	-10000	0	0
RAP1A	0.01	0	-10000	0	-10000	0	0
CDC42/GTP	-0.049	0.094	-10000	0	-0.41	8	8
Rap1/GTP	-0.051	0.096	-10000	0	-0.42	8	8
axon guidance	-0.045	0.11	-10000	0	-0.32	49	49
MAPK3	0.022	0.051	-10000	0	-10000	0	0
MAPK1	0.022	0.051	-10000	0	-10000	0	0
Rac1/GDP	0.004	0.08	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.041	0.078	-10000	0	-0.34	8	8
CDC42/GDP	0.004	0.08	-10000	0	-10000	0	0
PI3K	-0.002	0.022	-10000	0	-0.24	3	3
EFNA5	0.001	0.068	-10000	0	-0.51	6	6
Ephrin B2/EPHB4	-0.003	0.028	-10000	0	-0.3	3	3
Ephrin B/EPHB2/Intersectin/N-WASP	0.005	0.059	-10000	0	-10000	0	0
CDC42	0.01	0	-10000	0	-10000	0	0
RAS family/GTP	-0.049	0.094	-10000	0	-0.41	8	8
PTK2	0.016	0.029	-10000	0	-10000	0	0
MAP4K4	-0.036	0.13	-10000	0	-0.51	8	8
SRC	0.01	0	-10000	0	-10000	0	0
KALRN	0.005	0.047	-10000	0	-0.5	3	3
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.008	0.094	-10000	0	-0.34	1	1
MAP2K1	0.017	0.053	-10000	0	-10000	0	0
WASL	0.01	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.067	0.13	-10000	0	-0.3	78	78
cell migration	0.023	0.055	-10000	0	-10000	0	0
NRAS	0.01	0	-10000	0	-10000	0	0
SYNJ1	-0.009	0.095	-10000	0	-10000	0	0
PXN	0.01	0	-10000	0	-10000	0	0
TF	-0.068	0.15	-10000	0	-0.47	14	14
HRAS/GTP	-0.055	0.1	-10000	0	-0.45	8	8
Ephrin B1/EPHB1-2	-0.068	0.13	-10000	0	-0.31	78	78
cell adhesion mediated by integrin	0.001	0.046	0.27	7	-10000	0	7
RAC1	0.01	0	-10000	0	-10000	0	0
mol:GTP	-0.059	0.11	-10000	0	-0.48	8	8
RAC1-CDC42/GTP	-0.055	0.1	-10000	0	-0.44	10	10
RASA1	0.01	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.024	0.063	-10000	0	-10000	0	0
ruffle organization	-0.012	0.12	-10000	0	-0.42	8	8
NCK1	0.01	0	-10000	0	-10000	0	0
receptor internalization	-0.005	0.094	-10000	0	-10000	0	0
Ephrin B/EPHB2/KALRN	-0.039	0.092	-10000	0	-0.49	1	1
ROCK1	0.012	0.049	-10000	0	-0.28	10	10
RAS family/GDP	-0.038	0.073	-10000	0	-0.32	7	7
Rac1/GTP	-0.054	0.1	-10000	0	-0.44	8	8
Ephrin B/EPHB1/Src/Paxillin	0.007	0.058	-10000	0	-10000	0	0

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.016	0.086	-10000	0	-0.43	3	3
IKBKB	-0.001	0.048	-10000	0	-0.24	3	3
AKT1	-0.029	0.082	-10000	0	-0.26	3	3
IKBKG	0.001	0.05	-10000	0	-0.26	3	3
CALM1	-0.015	0.087	0.23	1	-0.64	4	5
PIK3CA	0.01	0	-10000	0	-10000	0	0
MAP3K1	-0.035	0.12	-10000	0	-0.57	3	3
MAP3K7	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	-0.022	0.092	0.23	1	-0.7	4	5
DOK1	0.01	0	-10000	0	-10000	0	0
AP-1	-0.006	0.061	0.15	1	-0.26	4	5
LYN	0.01	0	-10000	0	-10000	0	0
BLNK	0.008	0.027	-10000	0	-0.5	1	1
SHC1	0.01	0	-10000	0	-10000	0	0
BCR complex	-0.079	0.16	-10000	0	-0.4	70	70
CD22	-0.049	0.11	-10000	0	-0.56	7	7
CAMK2G	-0.008	0.081	0.22	1	-0.59	4	5
CSNK2A1	0.01	0	-10000	0	-10000	0	0
INPP5D	0.007	0.039	-10000	0	-0.5	2	2
SHC/GRB2/SOS1	-0.048	0.1	-10000	0	-0.44	8	8
GO:0007205	-0.022	0.094	0.23	1	-0.72	4	5
SYK	0.005	0.047	-10000	0	-0.5	3	3
ELK1	-0.015	0.089	0.23	1	-0.66	4	5
NFATC1	-0.056	0.12	-10000	0	-0.42	10	10
B-cell antigen/BCR complex	-0.079	0.16	-10000	0	-0.4	70	70
PAG1/CSK	0	0	-10000	0	-10000	0	0
NFKBIB	0.007	0.019	-10000	0	-10000	0	0
HRAS	-0.014	0.085	0.21	1	-0.59	4	5
NFKBIA	0.007	0.018	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.011	0.016	-10000	0	-10000	0	0
RasGAP/Csk	-0.054	0.11	-10000	0	-0.51	6	6
mol:GDP	-0.023	0.091	0.24	1	-0.7	4	5
PTEN	0.01	0	-10000	0	-10000	0	0
CD79B	-0.001	0.074	-10000	0	-0.52	7	7
NF-kappa-B/RelA/I kappa B alpha	0.011	0.016	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.065	0.14	-10000	0	-0.59	4	4
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	-0.029	0.093	0.21	2	-0.73	4	6
CSK	0.01	0	-10000	0	-10000	0	0
FOS	-0.026	0.11	0.23	1	-0.42	13	14
CHUK	0.001	0.05	-10000	0	-0.26	3	3
IBTK	0.01	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.031	0.077	-10000	0	-0.46	6	6
PTPN6	-0.046	0.099	-10000	0	-0.52	7	7
RELA	0.01	0	-10000	0	-10000	0	0
BCL2A1	0.01	0.02	-10000	0	-0.094	7	7
VAV2	-0.11	0.15	-10000	0	-0.37	68	68
ubiquitin-dependent protein catabolic process	0.01	0.018	-10000	0	-10000	0	0
BTK	-0.066	0.25	0.32	1	-1	22	23
CD19	-0.13	0.17	-10000	0	-0.42	67	67
MAP4K1	0.002	0.061	-10000	0	-0.5	5	5
CD72	0.007	0.039	-10000	0	-0.51	2	2
PAG1	0.01	0	-10000	0	-10000	0	0
MAPK14	-0.025	0.1	-10000	0	-0.56	2	2
SH3BP5	0.004	0.054	-10000	0	-0.5	4	4
PIK3AP1	-0.015	0.1	0.21	3	-0.64	6	9
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.014	0.12	-10000	0	-0.82	5	5
RAF1	-0.007	0.08	0.21	1	-0.54	4	5
RasGAP/p62DOK/SHIP	-0.052	0.11	-10000	0	-0.49	6	6
CD79A	-0.094	0.21	-10000	0	-0.52	69	69
re-entry into mitotic cell cycle	-0.006	0.061	0.15	1	-0.27	4	5
RASA1	0.01	0	-10000	0	-10000	0	0
MAPK3	0.006	0.069	-10000	0	-0.43	4	4
MAPK1	0.006	0.069	0.2	1	-0.43	4	5
CD72/SHP1	-0.015	0.1	-10000	0	-0.48	7	7
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.025	0.1	-10000	0	-0.47	3	3
actin cytoskeleton organization	-0.075	0.15	-10000	0	-0.33	67	67
NF-kappa-B/RelA	0.027	0.029	-10000	0	-10000	0	0
Calcineurin	-0.021	0.063	-10000	0	-0.52	4	4
PI3K	-0.098	0.13	-10000	0	-0.42	10	10
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.028	0.091	0.22	3	-0.72	4	7
SOS1	0.01	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.008	0.097	-10000	0	-0.68	4	4
DAPP1	-0.027	0.086	-10000	0	-0.88	2	2
cytokine secretion	-0.052	0.12	-10000	0	-0.4	10	10
mol:DAG	-0.029	0.093	0.21	2	-0.73	4	6
PLCG2	0.005	0.047	-10000	0	-0.5	3	3
MAP2K1	0	0.075	0.2	1	-0.49	4	5
B-cell antigen/BCR complex/FcgammaRIIB	-0.066	0.14	-10000	0	-0.33	70	70
mol:PI-3-4-5-P3	-0.075	0.094	-10000	0	-0.31	9	9
ETS1	-0.001	0.074	0.22	1	-0.52	4	5
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.057	0.12	-10000	0	-0.51	8	8
B-cell antigen/BCR complex/LYN	-0.04	0.092	-10000	0	-0.44	7	7
MALT1	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	-0.08	0.16	-10000	0	-0.34	67	67
B-cell antigen/BCR complex/LYN/SYK	-0.056	0.11	-10000	0	-0.43	13	13
CARD11	-0.028	0.1	0.23	1	-0.34	21	22
FCGR2B	0.01	0	-10000	0	-10000	0	0
PPP3CA	0.01	0	-10000	0	-10000	0	0
BCL10	0.01	0	-10000	0	-10000	0	0
IKK complex	0.005	0.025	-10000	0	-0.093	1	1
PTPRC	-0.002	0.076	-10000	0	-0.5	8	8
PDPK1	-0.032	0.081	-10000	0	-0.21	8	8
PPP3CB	0.01	0	-10000	0	-10000	0	0
PPP3CC	0.01	0	-10000	0	-10000	0	0
POU2F2	0.012	0.014	-10000	0	-0.098	2	2

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.008	0.079	-10000	0	-0.3	19	19
ACTA1	-0.001	0.1	-10000	0	-0.39	19	19
NUMA1	0.008	0.079	-10000	0	-0.3	19	19
SPTAN1	0.001	0.099	-10000	0	-0.38	19	19
LIMK1	0.001	0.099	-10000	0	-0.38	19	19
BIRC3	0.001	0.068	-10000	0	-0.52	6	6
BIRC2	0.01	0	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
CASP10	0.003	0.09	-10000	0	-0.35	20	20
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.01	0	-10000	0	-10000	0	0
PTK2	0.008	0.079	-10000	0	-0.3	19	19
DIABLO	0.01	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.002	0.098	-10000	0	-0.38	19	19
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.008	0.028	-10000	0	-0.52	1	1
GSN	0.001	0.1	-10000	0	-0.39	19	19
MADD	0.01	0	-10000	0	-10000	0	0
TFAP2A	-0.046	0.13	-10000	0	-0.63	16	16
BID	0.008	0.053	-10000	0	-0.21	19	19
MAP3K1	0.006	0.035	-10000	0	-0.2	4	4
TRADD	0.01	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	0.001	0.099	-10000	0	-0.38	19	19
CASP9	0.01	0	-10000	0	-10000	0	0
DNA repair	-0.004	0.027	0.15	3	-10000	0	3
neuron apoptosis	0.018	0.012	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.007	0.096	-10000	0	-0.37	19	19
APAF1	0.01	0	-10000	0	-10000	0	0
CASP6	0.018	0.049	-10000	0	-0.32	1	1
TRAF2	0.01	0	-10000	0	-10000	0	0
ICAD/CAD	0.007	0.096	-10000	0	-0.37	19	19
CASP7	-0.004	0.032	0.29	2	-10000	0	2
KRT18	0.012	0.016	-10000	0	-10000	0	0
apoptosis	0.011	0.085	-10000	0	-0.53	4	4
DFFA	0.001	0.099	-10000	0	-0.38	19	19
DFFB	0.001	0.099	-10000	0	-0.38	19	19
PARP1	0.004	0.027	-10000	0	-0.15	3	3
actin filament polymerization	-0.008	0.092	0.35	19	-10000	0	19
TNF	-0.015	0.11	-10000	0	-0.5	17	17
CYCS	0.01	0.038	-10000	0	-0.22	4	4
SATB1	0.019	0.062	-10000	0	-0.43	2	2
SLK	0.001	0.099	-10000	0	-0.38	19	19
p15 BID/BAX	0.012	0.047	-10000	0	-0.28	4	4
CASP2	0.028	0.048	-10000	0	-10000	0	0
JNK cascade	-0.006	0.035	0.2	4	-10000	0	4
CASP3	-0.005	0.1	-10000	0	-0.41	19	19
LMNB2	0.028	0.039	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
CASP4	0.01	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.005	0.035	-10000	0	-0.27	6	6
negative regulation of DNA binding	-0.045	0.13	-10000	0	-0.62	16	16
stress fiber formation	0.002	0.098	-10000	0	-0.38	19	19
GZMB	-0.006	0.1	-10000	0	-0.42	19	19
CASP1	0.012	0.025	-10000	0	-0.32	2	2
LMNB1	0.027	0.04	-10000	0	-0.22	1	1
APP	0.018	0.012	-10000	0	-10000	0	0
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.009	0	-10000	0	-10000	0	0
VIM	0.007	0.083	-10000	0	-0.31	19	19
LMNA	0.028	0.039	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.022	0.051	-10000	0	-10000	0	0
LRDD	0.007	0.039	-10000	0	-0.5	2	2
SREBF1	0.001	0.099	-10000	0	-0.38	19	19
APAF-1/Caspase 9	-0.002	0.016	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.008	0.078	-10000	0	-0.3	19	19
CFL2	0.007	0.095	-10000	0	-0.36	19	19
GAS2	-0.015	0.12	-10000	0	-0.35	30	30
positive regulation of apoptosis	0.03	0.04	-10000	0	-10000	0	0
PRF1	-0.009	0.097	-10000	0	-0.5	13	13

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.031	0.1	0.36	30	-10000	0	30
KIRREL	-0.007	0.086	-10000	0	-0.51	10	10
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.031	0.1	-10000	0	-0.36	30	30
PLCG1	0.01	0	-10000	0	-10000	0	0
ARRB2	0.01	0	-10000	0	-10000	0	0
WASL	0.01	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.022	0.071	-10000	0	-10000	0	0
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.009	0.053	-10000	0	-10000	0	0
FYN	-0.005	0.068	-10000	0	-0.25	10	10
mol:Ca2+	-0.022	0.071	-10000	0	-10000	0	0
mol:DAG	-0.022	0.071	-10000	0	-10000	0	0
NPHS2	-0.001	0.014	-10000	0	-10000	0	0
mol:IP3	-0.022	0.071	-10000	0	-10000	0	0
regulation of endocytosis	-0.018	0.058	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/Cholesterol	-0.022	0.073	-10000	0	-0.26	30	30
establishment of cell polarity	-0.031	0.1	-10000	0	-0.36	30	30
Nephrin/NEPH1/podocin/NCK1-2	-0.019	0.063	-10000	0	-10000	0	0
Nephrin/NEPH1/beta Arrestin2	-0.018	0.059	-10000	0	-10000	0	0
NPHS1	-0.023	0.12	-10000	0	-0.52	20	20
Nephrin/NEPH1/podocin	-0.02	0.064	-10000	0	-0.25	10	10
TJP1	0.01	0	-10000	0	-10000	0	0
NCK1	0.01	0	-10000	0	-10000	0	0
NCK2	0.01	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.022	0.071	-10000	0	-10000	0	0
CD2AP	0.01	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.022	0.071	-10000	0	-0.26	28	28
GRB2	0.01	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.023	0.1	-10000	0	-0.28	26	26
cytoskeleton organization	0.013	0.062	-10000	0	-10000	0	0
Nephrin/NEPH1	-0.022	0.071	-10000	0	-0.25	30	30
Nephrin/NEPH1/ZO-1	-0.024	0.078	-10000	0	-0.28	30	30

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.01	0	-9999	-10000	0	0
VLDLR	-0.002	0.076	-9999	-0.5	8	8
LRPAP1	0.01	0	-9999	-10000	0	0
NUDC	0.01	0	-9999	-10000	0	0
RELN/LRP8	-0.048	0.11	-9999	-0.3	57	57
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.01	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.02	0.11	-9999	-0.27	13	13
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.001	0.063	-9999	-0.52	5	5
IQGAP1	0.01	0	-9999	-10000	0	0
PLA2G7	0.001	0.068	-9999	-0.52	6	6
CALM1	0.01	0	-9999	-10000	0	0
DYNLT1	0.01	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.008	0.055	-9999	-0.37	8	8
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.01	0	-9999	-10000	0	0
CDK5R1	-0.005	0.088	-9999	-0.52	10	10
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.14	0.24	-9999	-0.52	101	101
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.052	0.12	-9999	-0.32	57	57
YWHAE	0.01	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.037	0.11	-9999	-0.33	15	15
MAP1B	-0.002	0.017	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.013	0.1	-9999	-10000	0	0
RELN	-0.062	0.18	-9999	-0.51	49	49
PAFAH/LIS1	0.015	0.042	-9999	-0.31	6	6
LIS1/CLIP170	0.021	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.046	0.067	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.016	0.1	-9999	-0.42	7	7
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.045	0.11	-9999	-0.35	15	15
LIS1/IQGAP1	0.021	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.018	0	-9999	-10000	0	0
PAFAH1B3	-0.017	0.12	-9999	-0.52	18	18
PAFAH1B2	0.01	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.018	0.012	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.06	0.083	-9999	-10000	0	0
LRP8	-0.002	0.079	-9999	-0.52	8	8
NDEL1/Katanin 60	-0.037	0.11	-9999	-0.33	15	15
P39/CDK5	-0.083	0.15	-9999	-0.48	15	15
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.021	0	-9999	-10000	0	0
CDK5	-0.011	0.1	-9999	-10000	0	0
PPP2R5D	0.01	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.01	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.043	0.1	-9999	-0.5	5	5
RELN/VLDLR	-0.048	0.11	-9999	-0.28	61	61
CDC42	0	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.024	0.09	-9999	-0.36	23	23
CRKL	0.008	0.073	-9999	-0.34	5	5
mol:PIP3	-0.016	0.005	-9999	-10000	0	0
AKT1	0.001	0.004	-9999	-10000	0	0
PTK2B	0.007	0.039	-9999	-0.5	2	2
RAPGEF1	0.014	0.07	-9999	-0.33	4	4
RANBP10	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.035	0.1	-9999	-0.32	38	38
MAP3K5	0.018	0.076	-9999	-0.37	5	5
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.031	0.092	-9999	-0.32	16	16
AP1	-0.031	0.09	-9999	-0.32	29	29
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
apoptosis	-0.046	0.2	-9999	-0.7	29	29
STAT3 (dimer)	0.009	0.078	-9999	-0.4	4	4
GAB1/CRKL/SHP2/PI3K	-0.017	0.054	-9999	-0.37	2	2
INPP5D	0.007	0.039	-9999	-0.5	2	2
CBL/CRK	0.014	0.07	-9999	-0.33	4	4
PTPN11	0.01	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.01	0	-9999	-10000	0	0
PTEN	0.01	0	-9999	-10000	0	0
ELK1	-0.011	0.048	-9999	-0.19	23	23
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.013	0.042	-9999	-0.25	3	3
PAK1	0.007	0.004	-9999	-10000	0	0
HGF/MET/RANBP10	-0.035	0.1	-9999	-0.32	38	38
HRAS	-0.005	0.12	-9999	-0.55	13	13
DOCK1	0.014	0.07	-9999	-0.33	4	4
GAB1	0.002	0.077	-9999	-0.29	15	15
CRK	0.008	0.073	-9999	-0.34	5	5
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.039	0.13	-9999	-0.5	25	25
JUN	0.007	0.039	-9999	-0.5	2	2
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.022	0.066	-9999	-0.23	25	25
PIK3R1	0.01	0	-9999	-10000	0	0
cell morphogenesis	0.031	0.081	-9999	-0.42	2	2
GRB2/SHC	-0.018	0.055	-9999	-0.24	13	13
FOS	-0.03	0.14	-9999	-0.5	27	27
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.011	0.048	-9999	-0.19	23	23
HGF/MET/MUC20	-0.035	0.1	-9999	-0.33	38	38
cell migration	-0.018	0.054	-9999	-0.23	13	13
GRB2	0.01	0	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
MET/RANBP10	-0.024	0.09	-9999	-0.36	23	23
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.003	0.08	-9999	-0.41	4	4
MET/MUC20	-0.024	0.092	-9999	-0.37	23	23
RAP1B	0.02	0.067	-9999	-0.36	2	2
RAP1A	0.02	0.067	-9999	-0.36	2	2
HGF/MET/RANBP9	-0.035	0.1	-9999	-0.32	38	38
RAF1	0.002	0.12	-9999	-0.52	13	13
STAT3	0.009	0.079	-9999	-0.4	4	4
cell proliferation	0.012	0.1	-9999	-0.34	25	25
RPS6KB1	0.002	0.027	-9999	-10000	0	0
MAPK3	-0.014	0.044	-9999	-10000	0	0
MAPK1	-0.014	0.044	-9999	-10000	0	0
RANBP9	0.01	0	-9999	-10000	0	0
MAPK8	0.032	0.065	-9999	-0.31	3	3
SRC	0.01	0.075	-9999	-0.38	4	4
PI3K	-0.018	0.055	-9999	-0.32	3	3
MET/Glomulin	-0.012	0.082	-9999	-0.32	23	23
SOS1	0.01	0	-9999	-10000	0	0
MAP2K1	0.008	0.11	-9999	-0.47	13	13
MET	-0.024	0.13	-9999	-0.51	23	23
MAP4K1	0.012	0.081	-9999	-0.36	7	7
PTK2	0.01	0	-9999	-10000	0	0
MAP2K2	0.008	0.11	-9999	-0.47	13	13
BAD	0.007	0.004	-9999	-10000	0	0
MAP2K4	0.024	0.071	-9999	-0.35	4	4
SHP2/GRB2/SOS1/GAB1	-0.023	0.072	-9999	-0.33	14	14
INPPL1	0.01	0	-9999	-10000	0	0
PXN	0.01	0	-9999	-10000	0	0
SH3KBP1	0.01	0	-9999	-10000	0	0
HGS	-0.003	0.065	-9999	-0.25	13	13
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.017	0.11	-9999	-0.51	18	18
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
PTPRJ	0.01	0	-9999	-10000	0	0
NCK/PLCgamma1	-0.018	0.057	-9999	-0.34	3	3
PDPK1	-0.007	0.004	-9999	-10000	0	0
HGF/MET/SHIP	-0.036	0.11	-9999	-0.34	38	38

×

S1P1 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.007	0.051	-9999	-0.36	7	7
PDGFRB	0.007	0.028	-9999	-0.51	1	1
SPHK1	-0.008	0.02	-9999	-10000	0	0
mol:S1P	-0.01	0.025	-9999	-10000	0	0
S1P1/S1P/Gi	-0.009	0.13	-9999	-0.36	32	32
GNAO1	0.005	0.048	-9999	-0.51	3	3
PDGFB-D/PDGFRB/PLCgamma1	-0.002	0.12	-9999	-0.48	7	7
PLCG1	-0.004	0.13	-9999	-0.34	31	31
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.007	0.028	-9999	-0.5	1	1
GNAI2	0.01	0.003	-9999	-10000	0	0
GNAI3	0.01	0.003	-9999	-10000	0	0
GNAI1	0.007	0.039	-9999	-0.51	2	2
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.007	0.046	-9999	-0.31	7	7
S1P1/S1P	-0.018	0.05	-9999	-0.33	4	4
negative regulation of cAMP metabolic process	-0.009	0.13	-9999	-0.35	32	32
MAPK3	-0.018	0.18	-9999	-0.54	31	31
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	-0.001	0.072	-9999	-0.51	7	7
PLCB2	0.012	0.069	-9999	-0.33	6	6
RAC1	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.015	0.043	-9999	-0.3	3	3
receptor internalization	-0.017	0.048	-9999	-0.31	4	4
PTGS2	-0.054	0.3	-9999	-0.98	31	31
Rac1/GTP	-0.015	0.043	-9999	-0.3	3	3
RHOA	0.01	0	-9999	-10000	0	0
VEGFA	0.009	0.003	-9999	-10000	0	0
negative regulation of T cell proliferation	-0.009	0.13	-9999	-0.35	32	32
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.031	0.14	-9999	-0.51	28	28
MAPK1	-0.018	0.18	-9999	-0.54	31	31
S1P1/S1P/PDGFB-D/PDGFRB	0.014	0.071	-9999	-0.35	4	4
ABCC1	0.01	0.002	-9999	-10000	0	0

×

LPA receptor mediated events

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
GNB1/GNG2	-0.001	0.014	-9999	-0.26	1	1
NF kappa B1 p50/RelA/I kappa B alpha	-0.025	0.069	-9999	-0.38	2	2
AP1	-0.041	0.09	-9999	-0.46	3	3
mol:PIP3	-0.027	0.069	-9999	-0.41	1	1
AKT1	-0.002	0.013	-9999	-10000	0	0
PTK2B	0.018	0.034	-9999	-0.27	2	2
RHOA	0.024	0.025	-9999	-10000	0	0
PIK3CB	0.009	0	-9999	-10000	0	0
mol:Ca2+	0.004	0.086	-9999	-0.38	3	3
MAGI3	0.002	0.061	-9999	-0.5	5	5
RELA	0.01	0	-9999	-10000	0	0
apoptosis	-0.006	0.083	-9999	-0.25	33	33
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.015	0.065	-9999	-0.27	5	5
NF kappa B1 p50/RelA	-0.024	0.071	-9999	-0.45	1	1
endothelial cell migration	0.022	0	-9999	-10000	0	0
ADCY4	0.011	0.071	-9999	-0.38	4	4
ADCY5	-0.004	0.09	-9999	-0.3	17	17
ADCY6	0.021	0.052	-9999	-0.35	1	1
ADCY7	0.02	0.052	-9999	-0.35	1	1
ADCY1	0.019	0.057	-9999	-0.31	3	3
ADCY2	0.006	0.075	-9999	-0.3	8	8
ADCY3	0.021	0.051	-9999	-0.35	1	1
ADCY8	-0.053	0.098	-9999	-0.3	12	12
ADCY9	0.017	0.064	-9999	-0.33	5	5
GSK3B	0.023	0.032	-9999	-0.25	2	2
arachidonic acid secretion	0.025	0.049	-9999	-0.32	1	1
GNG2	0.008	0.027	-9999	-0.5	1	1
TRIP6	0.018	0.022	-9999	-0.36	1	1
GNAO1	0.02	0.029	-9999	-0.3	3	3
HRAS	0.01	0	-9999	-10000	0	0
NFKBIA	0.012	0.096	-9999	-0.44	2	2
GAB1	0.008	0.027	-9999	-0.5	1	1
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.021	0.13	-9999	-0.84	9	9
JUN	0.007	0.039	-9999	-0.5	2	2
LPA/LPA2/NHERF2	-0.004	0.036	-9999	-0.3	5	5
TIAM1	-0.025	0.16	-9999	-0.98	9	9
PIK3R1	0.009	0	-9999	-10000	0	0
mol:IP3	0.004	0.088	-9999	-0.39	3	3
PLCB3	0.019	0.034	-9999	-0.26	5	5
FOS	-0.03	0.14	-9999	-0.5	27	27
positive regulation of mitosis	0.025	0.049	-9999	-0.32	1	1
LPA/LPA1-2-3	-0.028	0.081	-9999	-0.27	5	5
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.008	0.027	-9999	-0.5	1	1
stress fiber formation	0.017	0.052	-9999	-10000	0	0
GNAZ	-0.003	0.085	-9999	-0.29	28	28
EGFR/PI3K-beta/Gab1	-0.028	0.071	-9999	-0.43	1	1
positive regulation of dendritic cell cytokine production	-0.028	0.08	-9999	-0.27	5	5
LPA/LPA2/MAGI-3	-0.005	0.039	-9999	-0.3	6	6
ARHGEF1	0.031	0.014	-9999	-10000	0	0
GNAI2	0.022	0	-9999	-10000	0	0
GNAI3	0.022	0	-9999	-10000	0	0
GNAI1	0.021	0.024	-9999	-0.29	2	2
LPA/LPA3	-0.038	0.11	-9999	-0.36	37	37
LPA/LPA2	-0.001	0.02	-9999	-0.38	1	1
LPA/LPA1	0	0	-9999	-10000	0	0
HB-EGF/EGFR	-0.091	0.17	-9999	-0.32	114	114
HBEGF	-0.1	0.18	-9999	-0.37	110	110
mol:DAG	0.004	0.088	-9999	-0.39	3	3
cAMP biosynthetic process	0.007	0.061	-9999	-0.37	1	1
NFKB1	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
GNB1	0.009	0	-9999	-10000	0	0
LYN	0.012	0.096	-9999	-0.44	2	2
GNAQ	-0.011	0.089	-9999	-0.27	33	33
LPAR2	0.008	0.028	-9999	-0.52	1	1
LPAR3	-0.044	0.16	-9999	-0.51	37	37
LPAR1	0.014	0	-9999	-10000	0	0
IL8	-0.038	0.14	-9999	-0.39	17	17
PTK2	0.003	0.083	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.006	0.084	-9999	-0.26	33	33
EGFR	-0.005	0.087	-9999	-0.52	10	10
PLCG1	-0.008	0.098	-9999	-0.29	34	34
PLD2	0.003	0.083	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
PI3K-beta	-0.002	0.015	-9999	-10000	0	0
cell migration	-0.014	0.046	-9999	-0.25	9	9
SLC9A3R2	0.004	0.054	-9999	-0.5	4	4
PXN	0.017	0.052	-9999	-10000	0	0
HRAS/GTP	0.023	0.05	-9999	-0.32	1	1
RAC1	0.01	0	-9999	-10000	0	0
MMP9	-0.081	0.2	-9999	-0.52	60	60
PRKCE	0.005	0.047	-9999	-0.51	3	3
PRKCD	0.01	0.084	-9999	-0.42	2	2
Gi(beta/gamma)	0.023	0.051	-9999	-0.34	1	1
mol:LPA	0.004	0.001	-9999	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.021	0.063	-9999	-10000	0	0
MAPKKK cascade	0.025	0.049	-9999	-0.32	1	1
contractile ring contraction involved in cytokinesis	0.024	0.025	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.02	0.1	-9999	-0.28	43	43
GNA15	-0.01	0.084	-9999	-0.26	33	33
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
MAPT	0.015	0.066	-9999	-0.27	5	5
GNA11	-0.011	0.088	-9999	-0.27	34	34
Rac1/GTP	-0.022	0.14	-9999	-0.89	9	9
MMP2	0.023	0	-9999	-10000	0	0

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.18	0.26	-10000	0	-0.52	127	127
mol:Halofuginone	0.004	0	-10000	0	-10000	0	0
ITGA1	0.008	0.027	-10000	0	-0.5	1	1
CDKN1A	0.015	0.048	-10000	0	-0.61	1	1
PRL-3/alpha Tubulin	-0.001	0.02	-10000	0	-0.37	1	1
mol:Ca2+	-0.057	0.14	-10000	0	-0.38	53	53
AGT	-0.07	0.19	-10000	0	-0.52	53	53
CCNA2	-0.064	0.15	-10000	0	-0.5	12	12
TUBA1B	0.01	0	-10000	0	-10000	0	0
EGR1	-0.008	0.097	-10000	0	-0.35	26	26
CDK2/Cyclin E1	-0.094	0.13	-10000	0	-0.38	15	15
MAPK3	0.017	0.021	-10000	0	-0.37	1	1
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.017	0.021	-10000	0	-0.37	1	1
PTP4A1	0.009	0.074	-10000	0	-10000	0	0
PTP4A3	0.008	0.028	-10000	0	-0.52	1	1
PTP4A2	0.01	0	-10000	0	-10000	0	0
ITGB1	0.017	0.021	-10000	0	-0.37	1	1
SRC	0.01	0	-10000	0	-10000	0	0
RAC1	0.017	0.035	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.012	0.07	-10000	0	-10000	0	0
RABGGTA	0.01	0	-10000	0	-10000	0	0
BCAR1	0	0.023	0.21	1	-0.37	1	2
RHOC	0.017	0.035	-10000	0	-10000	0	0
RHOA	0.017	0.035	-10000	0	-10000	0	0
cell motility	0.02	0.038	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.013	0.069	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.002	0.027	-10000	0	-0.36	2	2
ROCK1	0.02	0.038	-10000	0	-10000	0	0
RABGGTB	0.01	0	-10000	0	-10000	0	0
CDK2	0.01	0	-10000	0	-10000	0	0
mitosis	0.009	0.074	-10000	0	-10000	0	0
ATF5	0.008	0.028	-10000	0	-0.52	1	1

×

BARD1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.003	0.034	-10000	0	-0.37	3	3
ATM	0.01	0	-10000	0	-10000	0	0
UBE2D3	0.01	0	-10000	0	-10000	0	0
PRKDC	0.01	0	-10000	0	-10000	0	0
ATR	0.01	0	-10000	0	-10000	0	0
UBE2L3	0.01	0	-10000	0	-10000	0	0
FANCD2	0.019	0.015	-10000	0	-10000	0	0
protein ubiquitination	-0.092	0.12	-10000	0	-0.51	3	3
XRCC5	0.01	0	-10000	0	-10000	0	0
XRCC6	0.01	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.01	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.005	0.017	-10000	0	-10000	0	0
FANCF	0.01	0	-10000	0	-10000	0	0
BRCA1	0.008	0.028	-10000	0	-0.52	1	1
CCNE1	-0.18	0.26	-10000	0	-0.52	127	127
CDK2/Cyclin E1	-0.13	0.18	-10000	0	-0.37	127	127
FANCG	0.01	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.004	0.039	-10000	0	-0.37	4	4
FANCE	0.01	0	-10000	0	-10000	0	0
FANCC	0.01	0	-10000	0	-10000	0	0
NBN	0.01	0	-10000	0	-10000	0	0
FANCA	-0.004	0.084	-10000	0	-0.52	9	9
DNA repair	-0.021	0.13	-10000	0	-0.46	5	5
BRCA1/BARD1/ubiquitin	-0.004	0.039	-10000	0	-0.37	4	4
BARD1/DNA-PK	-0.002	0.025	-10000	0	-0.27	2	2
FANCL	0.01	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.003	0.034	0.36	3	-10000	0	3
BRCA1/BARD1/CTIP/M/R/N Complex	0.03	0.018	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	-0.003	0.032	-10000	0	-0.3	4	4
BRCA1/BARD1/P53	-0.003	0.029	-10000	0	-0.27	3	3
BARD1/CSTF1/BRCA1	-0.003	0.032	-10000	0	-0.3	4	4
BRCA1/BACH1	0.008	0.028	-10000	0	-0.52	1	1
BARD1	0.005	0.048	-10000	0	-0.52	3	3
PCNA	0.008	0.028	-10000	0	-0.52	1	1
BRCA1/BARD1/UbcH5C	-0.003	0.032	-10000	0	-0.3	4	4
BRCA1/BARD1/UbcH7	-0.003	0.032	-10000	0	-0.3	4	4
BRCA1/BARD1/RAD51/PCNA	-0.058	0.12	-10000	0	-0.55	4	4
BARD1/DNA-PK/P53	-0.002	0.023	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.004	0.039	-10000	0	-0.37	4	4
BRCA1/BARD1/CTIP	-0.003	0.029	-10000	0	-10000	0	0
FA complex	0.028	0.024	-10000	0	-10000	0	0
BARD1/EWS	-0.003	0.034	-10000	0	-0.37	3	3
RBBP8	0.018	0	-10000	0	-10000	0	0
TP53	0.01	0	-10000	0	-10000	0	0
TOPBP1	0.01	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.003	0.028	0.27	3	-10000	0	3
BRCA1/BARD1	-0.093	0.12	-10000	0	-0.52	3	3
CSTF1	0.01	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.003	0.034	-10000	0	-0.37	3	3
CDK2	0.01	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.096	0.21	-10000	0	-0.52	70	70
RAD50	0.01	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.004	0.039	-10000	0	-0.37	4	4
EWSR1	0.01	0	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	-0.001	0.02	-10000	0	-0.37	1	1
PRKCZ	0.007	0.039	-10000	0	-0.5	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.01	0.037	-10000	0	-0.26	1	1
IRAK/TOLLIP	0.01	0.024	-10000	0	-0.28	2	2
IKBKB	0.01	0	-10000	0	-10000	0	0
IKBKG	0.01	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.12	0.18	-10000	0	-0.37	117	117
IL1A	-0.14	0.23	-10000	0	-0.5	102	102
IL1B	-0.005	0.091	-10000	0	-0.36	22	22
IRAK/TRAF6/p62/Atypical PKCs	-0.002	0.023	-10000	0	-10000	0	0
IL1R2	-0.017	0.12	-10000	0	-0.52	18	18
IL1R1	0.007	0.039	-10000	0	-0.5	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.004	0.045	0.19	7	-0.38	1	8
TOLLIP	0.01	0	-10000	0	-10000	0	0
TICAM2	0.008	0.027	-10000	0	-0.5	1	1
MAP3K3	0.008	0.027	-10000	0	-0.5	1	1
TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.049	0.019	-10000	0	-10000	0	0
JUN	0.026	0.051	-10000	0	-0.43	1	1
MAP3K7	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.015	0.059	-10000	0	-0.47	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.077	0.12	-10000	0	-0.36	3	3
PIK3R1	0.01	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.07	0.11	-10000	0	-0.49	1	1
IL1 beta fragment/IL1R1/IL1RAP	-0.018	0.069	-10000	0	-0.4	2	2
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	0.022	0.047	-10000	0	-10000	0	0
IRAK1	0.016	0.025	-10000	0	-0.31	2	2
IL1RN/IL1R1	-0.01	0.059	-10000	0	-0.36	10	10
IRAK4	0.01	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.019	0.051	-10000	0	-0.39	1	1
CHUK	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.018	0.069	-10000	0	-0.4	2	2
IL1 beta/IL1R2	-0.034	0.1	-10000	0	-0.33	36	36
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.018	-10000	0	-0.24	1	1
NF kappa B1 p50/RelA	-0.013	0.052	-10000	0	-0.43	1	1
IRAK3	-0.003	0.081	-10000	0	-0.5	9	9
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.016	0.06	-10000	0	-0.47	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.044	0.12	-10000	0	-0.46	1	1
IL1 alpha/IL1R1/IL1RAP	-0.087	0.14	-10000	0	-0.3	103	103
RELA	0.01	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.01	0	-10000	0	-10000	0	0
MYD88	0.01	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	-0.002	0.023	-10000	0	-0.26	1	1
IL1RAP	0.01	0	-10000	0	-10000	0	0
UBE2N	0.01	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.014	0.05	-10000	0	-0.39	1	1
CASP1	0.007	0.039	-10000	0	-0.5	2	2
IL1RN/IL1R2	-0.027	0.098	-10000	0	-0.38	25	25
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.016	0.063	-10000	0	-0.49	1	1
TMEM189-UBE2V1	0.003	0.028	-10000	0	-0.52	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.051	0.081	-10000	0	-0.39	2	2
PIK3CA	0.01	0	-10000	0	-10000	0	0
IL1RN	-0.002	0.077	-10000	0	-0.51	8	8
TRAF6/TAK1/TAB1/TAB2	-0.001	0.013	-10000	0	-0.24	1	1
MAP2K6	0.017	0.049	-10000	0	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.016	0.078	-10000	0	-0.59	5	5
FYN	0.037	0.12	-10000	0	-0.66	7	7
LAT/GRAP2/SLP76	-0.013	0.1	-10000	0	-0.54	9	9
IKBKB	0.01	0	-10000	0	-10000	0	0
AKT1	0.041	0.088	-10000	0	-0.46	7	7
B2M	0.011	0.003	-10000	0	-10000	0	0
IKBKG	-0.007	0.022	-10000	0	-0.13	4	4
MAP3K8	0.007	0.039	-10000	0	-0.5	2	2
mol:Ca2+	-0.009	0.023	-10000	0	-0.1	6	6
integrin-mediated signaling pathway	-0.002	0.023	-10000	0	-0.3	2	2
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.039	0.13	-10000	0	-0.66	8	8
TRPV6	-0.073	0.18	-10000	0	-0.51	50	50
CD28	0.01	0.002	-10000	0	-10000	0	0
SHC1	0.036	0.12	-10000	0	-0.7	6	6
receptor internalization	0.027	0.12	-10000	0	-0.72	7	7
PRF1	-0.003	0.23	-10000	0	-1.1	15	15
KRAS	0.01	0	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
COT/AKT1	0.041	0.076	-10000	0	-0.39	7	7
LAT	0.035	0.12	-10000	0	-0.79	5	5
EntrezGene:6955	0.001	0.004	-10000	0	-10000	0	0
CD3D	0.008	0.04	-10000	0	-0.52	2	2
CD3E	0.008	0.04	-10000	0	-0.52	2	2
CD3G	0.003	0.061	-10000	0	-0.51	5	5
RASGRP2	0.001	0.045	-10000	0	-0.16	24	24
RASGRP1	0.041	0.096	-10000	0	-0.42	10	10
HLA-A	0.011	0.003	-10000	0	-10000	0	0
RASSF5	0.007	0.039	-10000	0	-0.5	2	2
RAP1A/GTP/RAPL	-0.002	0.023	-10000	0	-0.3	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.03	0.036	-10000	0	-0.12	9	9
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.013	0.039	-10000	0	-0.22	6	6
PRKCA	-0.004	0.05	-10000	0	-0.27	7	7
GRAP2	-0.005	0.085	-10000	0	-0.5	10	10
mol:IP3	0.012	0.1	0.21	46	-0.44	7	53
EntrezGene:6957	0.001	0.004	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.019	0.12	-10000	0	-0.8	5	5
ORAI1	0.041	0.099	0.29	50	-10000	0	50
CSK	0.034	0.12	-10000	0	-0.8	5	5
B7 family/CD28	-0.029	0.12	-10000	0	-0.64	11	11
CHUK	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.029	0.14	-10000	0	-0.71	8	8
PTPN6	0.033	0.11	-10000	0	-0.7	6	6
VAV1	0.033	0.12	-10000	0	-0.67	8	8
Monovalent TCR/CD3	0.012	0.083	-10000	0	-0.43	8	8
CBL	0.01	0	-10000	0	-10000	0	0
LCK	0.034	0.12	-10000	0	-0.68	7	7
PAG1	0.034	0.12	-10000	0	-0.8	5	5
RAP1A	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.028	0.13	-10000	0	-0.74	7	7
CD80	-0.002	0.077	-10000	0	-0.51	8	8
CD86	0.001	0.067	-10000	0	-0.51	6	6
PDK1/CARD11/BCL10/MALT1	-0.015	0.047	-10000	0	-0.27	6	6
HRAS	0.01	0	-10000	0	-10000	0	0
GO:0035030	0.029	0.12	-10000	0	-0.52	11	11
CD8A	0.005	0.056	-10000	0	-0.52	4	4
CD8B	0.001	0.074	-10000	0	-0.52	7	7
PTPRC	-0.002	0.077	-10000	0	-0.51	8	8
PDK1/PKC theta	0.038	0.12	-10000	0	-0.49	11	11
CSK/PAG1	0.038	0.11	-10000	0	-0.77	5	5
SOS1	0.01	0	-10000	0	-10000	0	0
peptide-MHC class I	0.016	0.006	-10000	0	-10000	0	0
GRAP2/SLP76	-0.016	0.12	-10000	0	-0.6	10	10
STIM1	0.021	0.049	-10000	0	-10000	0	0
RAS family/GTP	0.041	0.039	-10000	0	-0.17	5	5
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.026	0.14	-10000	0	-0.79	7	7
mol:DAG	-0.004	0.072	-10000	0	-0.4	7	7
RAP1A/GDP	0.014	0.015	-10000	0	-0.063	1	1
PLCG1	0.01	0	-10000	0	-10000	0	0
CD247	0.005	0.055	-10000	0	-0.51	4	4
cytotoxic T cell degranulation	-0.001	0.22	-10000	0	-1	15	15
RAP1A/GTP	-0.004	0.015	-10000	0	-0.065	5	5
mol:PI-3-4-5-P3	0.041	0.1	-10000	0	-0.56	7	7
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.009	0.12	0.23	43	-0.59	7	50
NRAS	0.01	0	-10000	0	-10000	0	0
ZAP70	0.001	0.067	-10000	0	-0.51	6	6
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.013	0.099	-10000	0	-0.6	7	7
MALT1	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
CD8 heterodimer	0.005	0.078	-10000	0	-0.49	8	8
CARD11	-0.016	0.11	-10000	0	-0.52	17	17
PRKCB	-0.005	0.06	-10000	0	-0.3	10	10
PRKCE	-0.004	0.051	-10000	0	-0.28	6	6
PRKCQ	0.031	0.13	-10000	0	-0.53	13	13
LCP2	0.007	0.039	-10000	0	-0.5	2	2
BCL10	0.01	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.041	0.076	-10000	0	-0.38	7	7
IKK complex	0.039	0.032	-10000	0	-0.11	7	7
RAS family/GDP	-0.001	0.005	-10000	0	-10000	0	0
MAP3K14	0.041	0.059	-10000	0	-0.29	7	7
PDPK1	0.043	0.084	-10000	0	-0.43	7	7
TCR/CD3/MHC I/CD8/Fyn	0.026	0.13	-10000	0	-0.97	5	5

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.024	0.091	-9999	-0.37	23	23
AKT1	0.034	0.11	-9999	-0.51	8	8
PTK2B	-0.008	0.13	-9999	-0.6	9	9
VEGFR2 homodimer/Frs2	-0.041	0.13	-9999	-0.74	7	7
CAV1	-0.3	0.25	-9999	-0.5	214	214
CALM1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.037	0.12	-9999	-0.68	7	7
endothelial cell proliferation	0.041	0.11	-9999	-0.48	8	8
mol:Ca2+	0.009	0.12	-9999	-0.57	8	8
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.033	0.1	-9999	-0.61	7	7
RP11-342D11.1	0.002	0.12	-9999	-0.57	8	8
CDH5	-0.053	0.17	-9999	-0.5	43	43
VEGFA homodimer	0	0	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
SHC2	0.001	0.066	-9999	-0.5	6	6
HRAS/GDP	-0.026	0.086	-9999	-0.48	8	8
SH2D2A	0.008	0.028	-9999	-0.52	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.029	0.091	-9999	-0.49	9	9
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.036	0.11	-9999	-0.64	7	7
VEGFR1 homodimer	0.01	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.029	0.095	-9999	-0.54	8	8
GRB10	0.009	0.12	-9999	-0.56	8	8
PTPN11	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
PAK1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.059	0.15	-9999	-0.56	23	23
HRAS	0.01	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.008	0.083	-9999	-0.36	8	8
HIF1A	0.01	0	-9999	-10000	0	0
FRS2	0.007	0.04	-9999	-0.52	2	2
oxygen and reactive oxygen species metabolic process	-0.032	0.1	-9999	-0.6	7	7
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.003	0.081	-9999	-0.5	9	9
Nck/Pak	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.035	0.11	-9999	-0.64	7	7
mol:GDP	-0.028	0.092	-9999	-0.52	8	8
mol:NADP	0.028	0.1	-9999	-0.43	9	9
eNOS/Hsp90	0.032	0.095	-9999	-0.44	5	5
PIK3R1	0.01	0	-9999	-10000	0	0
mol:IP3	0.009	0.12	-9999	-0.57	8	8
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0.008	0.027	-9999	-0.5	1	1
VEGFA	0.011	0	-9999	-10000	0	0
VEGFC	0.005	0.048	-9999	-0.51	3	3
FAK1/Vinculin	0.009	0.13	-9999	-0.61	9	9
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.048	0.12	-9999	-0.62	8	8
PTPN6	0.01	0	-9999	-10000	0	0
EPAS1	-0.04	0.16	-9999	-0.49	40	40
mol:L-citrulline	0.028	0.1	-9999	-0.43	9	9
ITGAV	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.034	0.11	-9999	-0.64	7	7
VEGFR2 homodimer/VEGFA homodimer	-0.036	0.11	-9999	-0.62	8	8
VEGFR2/3 heterodimer	-0.047	0.14	-9999	-0.67	11	11
VEGFB	0.01	0	-9999	-10000	0	0
MAPK11	0.01	0.12	-9999	-0.59	8	8
VEGFR2 homodimer	-0.022	0.15	-9999	-0.73	8	8
FLT1	0.01	0	-9999	-10000	0	0
NEDD4	0.01	0.027	-9999	-0.5	1	1
MAPK3	0.014	0.11	-9999	-0.53	8	8
MAPK1	0.014	0.11	-9999	-0.53	8	8
VEGFA145/NRP2	-0.002	0.027	-9999	-0.36	2	2
VEGFR1/2 heterodimer	-0.04	0.12	-9999	-0.7	7	7
KDR	-0.022	0.15	-9999	-0.74	8	8
VEGFA165/NRP1/VEGFR2 homodimer	-0.033	0.11	-9999	-0.6	8	8
SRC	0.01	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.015	0.11	-9999	-0.54	8	8
PI3K	-0.032	0.1	-9999	-0.58	8	8
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.035	0.11	-9999	-0.64	7	7
FES	0.008	0.12	-9999	-0.58	8	8
GAB1	-0.033	0.11	-9999	-0.62	7	7
VEGFR2 homodimer/VEGFA homodimer/Src	-0.035	0.11	-9999	-0.64	7	7
CTNNB1	0.01	0	-9999	-10000	0	0
SOS1	0.01	0	-9999	-10000	0	0
ARNT	0.01	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.1	0.14	-9999	-0.51	11	11
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.035	0.11	-9999	-0.64	7	7
PI3K/GAB1	0.034	0.12	-9999	-0.52	8	8
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.032	0.1	-9999	-0.62	7	7
PRKACA	0.01	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.045	0.13	-9999	-0.61	12	12
HSP90AA1	0.01	0	-9999	-10000	0	0
CDC42	0.008	0.12	-9999	-0.58	8	8
actin cytoskeleton reorganization	-0.036	0.11	-9999	-0.64	7	7
PTK2	0.003	0.14	-9999	-0.66	9	9
EDG1	0.002	0.12	-9999	-0.57	8	8
mol:DAG	0.009	0.12	-9999	-0.57	8	8
CaM/Ca2+	-0.029	0.094	-9999	-0.52	8	8
MAP2K3	0.015	0.11	-9999	-0.55	8	8
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.033	0.11	-9999	-0.59	8	8
PLCG1	0.008	0.12	-9999	-0.58	8	8
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.033	0.11	-9999	-0.59	8	8
IQGAP1	0.01	0	-9999	-10000	0	0
YES1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.035	0.11	-9999	-0.64	7	7
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.035	0.11	-9999	-0.64	7	7
cell migration	0.016	0.14	-9999	-0.6	8	8
mol:PI-3-4-5-P3	-0.03	0.096	-9999	-0.53	8	8
FYN	0.01	0	-9999	-10000	0	0
VEGFB/NRP1	-0.03	0.097	-9999	-0.54	8	8
mol:NO	0.028	0.1	-9999	-0.43	9	9
PXN	0.01	0	-9999	-10000	0	0
HRAS/GTP	-0.026	0.085	-9999	-0.48	8	8
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.033	0.11	-9999	-0.59	8	8
VHL	0.01	0	-9999	-10000	0	0
ITGB3	-0.025	0.13	-9999	-0.52	23	23
NOS3	0.028	0.11	-9999	-0.49	9	9
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.04	0.12	-9999	-0.64	9	9
RAC1	0.01	0	-9999	-10000	0	0
PRKCA	0.014	0.11	-9999	-0.53	8	8
PRKCB	0.011	0.12	-9999	-0.55	9	9
VCL	0.01	0	-9999	-10000	0	0
VEGFA165/NRP1	0.001	0.12	-9999	-0.57	8	8
VEGFR1/2 heterodimer/VEGFA homodimer	-0.035	0.11	-9999	-0.64	7	7
VEGFA165/NRP2	-0.002	0.027	-9999	-0.36	2	2
MAPKKK cascade	-0.026	0.084	-9999	-0.49	7	7
NRP2	0.007	0.039	-9999	-0.5	2	2
VEGFC homodimer	0.005	0.048	-9999	-0.51	3	3
NCK1	0.01	0	-9999	-10000	0	0
ROCK1	0.01	0	-9999	-10000	0	0
FAK1/Paxillin	0.009	0.13	-9999	-0.64	8	8
MAP3K13	0.008	0.12	-9999	-0.58	8	8
PDPK1	0.031	0.1	-9999	-0.47	8	8

×

IL2 signaling events mediated by STAT5

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
GAB2	0.005	0.054	-9999	-0.5	4	4
ELF1	-0.003	0.064	-9999	-0.33	1	1
CCNA2	-0.14	0.24	-9999	-0.52	98	98
PIK3CA	0.01	0	-9999	-10000	0	0
JAK3	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
JAK1	0.01	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.049	0.051	-9999	-0.51	1	1
SHC1	0.01	0	-9999	-10000	0	0
SP1	0.009	0.048	-9999	-0.33	7	7
IL2RA	-0.011	0.12	-9999	-0.4	30	30
IL2RB	0.007	0.039	-9999	-0.5	2	2
SOS1	0.01	0	-9999	-10000	0	0
IL2RG	0.005	0.054	-9999	-0.5	4	4
G1/S transition of mitotic cell cycle	-0.024	0.13	-9999	-0.68	8	8
PTPN11	0.01	0	-9999	-10000	0	0
CCND2	0.009	0.1	-9999	-0.73	7	7
LCK	0.007	0.039	-9999	-0.51	2	2
GRB2	0.01	0	-9999	-10000	0	0
IL2	0.006	0.005	-9999	-10000	0	0
CDK6	0.007	0.039	-9999	-0.51	2	2
CCND3	0.053	0.046	-9999	-0.43	1	1

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.005	0.048	-9999	-0.51	3	3
CDC42/GTP	-0.03	0.073	-9999	-0.41	3	3
PLCG1	-0.003	0.087	-9999	-0.42	3	3
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.01	0	-9999	-10000	0	0
GNAI3	0.01	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.029	0.072	-9999	-0.4	3	3
S1PR5	-0.025	0.13	-9999	-0.5	24	24
S1PR4	-0.025	0.13	-9999	-0.5	24	24
MAPK3	-0.003	0.087	-9999	-0.42	3	3
MAPK1	-0.003	0.087	-9999	-0.42	3	3
S1P/S1P5/Gi	-0.01	0.096	-9999	-0.46	5	5
GNAI1	0.007	0.039	-9999	-0.5	2	2
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.021	0.076	-9999	-0.3	24	24
RHOA	0.007	0.067	-9999	-0.24	24	24
S1P/S1P4/Gi	-0.01	0.092	-9999	-0.45	3	3
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.031	0.14	-9999	-0.5	28	28
S1P/S1P4/G12/G13	-0.018	0.067	-9999	-0.27	24	24
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.015	0.004	-9999	-10000	0	0
RAS family/GTP	-0.036	0.073	-9999	-10000	0	0
NFATC4	-0.003	0.084	-9999	-0.32	1	1
ERBB2IP	0.01	0.002	-9999	-10000	0	0
HSP90 (dimer)	0.01	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.043	0.089	-9999	-0.42	1	1
JUN	0.021	0.064	-9999	-0.25	2	2
HRAS	0.01	0.001	-9999	-10000	0	0
DOCK7	-0.013	0.099	-9999	-0.4	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.049	0.1	-9999	-0.51	1	1
AKT1	0.009	0.003	-9999	-10000	0	0
BAD	0.016	0.002	-9999	-10000	0	0
MAPK10	-0.038	0.072	-9999	-0.27	16	16
mol:GTP	0	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.02	0.11	-9999	-0.46	1	1
RAF1	0.007	0.091	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 2	-0.037	0.094	-9999	-0.27	48	48
STAT3	0.001	0.001	-9999	-10000	0	0
cell migration	0	0.078	-9999	-0.22	16	16
mol:PI-3-4-5-P3	-0.001	0.002	-9999	-10000	0	0
cell proliferation	-0.005	0.17	-9999	-0.57	11	11
FOS	-0.008	0.17	-9999	-0.45	35	35
NRAS	0.01	0.001	-9999	-10000	0	0
mol:Ca2+	-0.043	0.089	-9999	-0.42	1	1
MAPK3	0.002	0.13	-9999	-0.48	8	8
MAPK1	0.002	0.13	-9999	-0.48	8	8
JAK2	-0.013	0.099	-9999	-0.4	1	1
NF2	-0.002	0.004	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.026	0.1	-9999	-0.24	66	66
NRG1	-0.085	0.2	-9999	-0.5	65	65
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.014	0.11	-9999	-0.34	1	1
MAPK9	-0.021	0.044	-9999	-0.2	1	1
ERBB2	-0.002	0.029	-9999	-0.39	2	2
ERBB3	0.005	0.039	-9999	-0.5	2	2
SHC1	0.01	0.002	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
apoptosis	0.001	0.007	-9999	-10000	0	0
STAT3 (dimer)	0.001	0.001	-9999	-10000	0	0
RNF41	0.018	0.009	-9999	-10000	0	0
FRAP1	0.007	0.002	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.029	0.061	-9999	-0.28	1	1
ErbB2/ErbB2/HSP90 (dimer)	-0.002	0.024	-9999	-0.32	2	2
CHRNA1	0.001	0.14	-9999	-0.56	9	9
myelination	-0.001	0.084	-9999	-0.31	1	1
PPP3CB	-0.012	0.093	-9999	-0.37	1	1
KRAS	0.01	0.001	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.038	0.079	-9999	-0.28	1	1
NRG2	-0.055	0.17	-9999	-0.5	44	44
mol:GDP	-0.026	0.1	-9999	-0.24	66	66
SOS1	0.01	0.001	-9999	-10000	0	0
MAP2K2	0.014	0.091	-9999	-0.31	3	3
SRC	0.01	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.001	-9999	-10000	0	0
PTPN11	-0.013	0.098	-9999	-0.4	1	1
MAP2K1	-0.011	0.14	-9999	-0.47	8	8
heart morphogenesis	-0.043	0.089	-9999	-0.42	1	1
RAS family/GDP	-0.036	0.074	-9999	-10000	0	0
GRB2	0.01	0.001	-9999	-10000	0	0
PRKACA	-0.003	0.007	-9999	-10000	0	0
CHRNE	0.012	0.02	-9999	-0.17	2	2
HSP90AA1	0.01	0	-9999	-10000	0	0
activation of caspase activity	-0.009	0.003	-9999	-10000	0	0
nervous system development	-0.043	0.089	-9999	-0.42	1	1
CDC42	0.01	0	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	-0.001	0.016	-9999	-0.3	1	1
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.01	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.008	0.096	-9999	-0.52	12	12
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.01	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.003	0.046	-9999	-0.2	4	4
response to UV	0	0	-9999	-10000	0	0
YES1	0.01	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	0.008	0.027	-9999	-0.5	1	1
FYN	0.01	0	-9999	-10000	0	0
MAP3K12	0.01	0	-9999	-10000	0	0
FGR	-0.037	0.15	-9999	-0.5	32	32
p38 alpha/TAB1	-0.014	0.046	-9999	-0.27	6	6
PRKG1	-0.037	0.15	-9999	-0.5	32	32
DUSP8	0	0.072	-9999	-0.5	7	7
PGK/cGMP/p38 alpha	-0.031	0.086	-9999	-0.37	15	15
apoptosis	-0.014	0.044	-9999	-0.29	4	4
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.01	0	-9999	-10000	0	0
DUSP1	-0.037	0.15	-9999	-0.5	32	32
PAK1	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.001	0.014	-9999	-0.26	1	1
TRAF6	0.01	0	-9999	-10000	0	0
RAC1	0.01	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	0.01	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.011	0.092	-9999	-0.36	13	13
BLK	-0.054	0.17	-9999	-0.52	42	42
HCK	-0.011	0.1	-9999	-0.5	14	14
MAP2K3	0.01	0	-9999	-10000	0	0
DUSP16	0.01	0	-9999	-10000	0	0
DUSP10	0.008	0.027	-9999	-0.5	1	1
TRAF6/MEKK3	-0.001	0.015	-9999	-0.27	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.019	0.063	-9999	-0.33	4	4
positive regulation of innate immune response	0.016	0.095	-9999	-0.38	12	12
LCK	0.007	0.039	-9999	-0.51	2	2
p38alpha-beta/MKP7	0.021	0.091	-9999	-0.42	7	7
p38alpha-beta/MKP5	0.02	0.093	-9999	-0.4	8	8
PGK/cGMP	-0.033	0.1	-9999	-0.36	32	32
PAK2	0.01	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.001	0.12	-9999	-0.44	12	12
CDC42	0.01	0	-9999	-10000	0	0
RALB	0.01	0	-9999	-10000	0	0
RALA	0.01	0	-9999	-10000	0	0
PAK3	-0.066	0.18	-9999	-0.52	50	50

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.002	0.061	-9999	-0.51	5	5
CLTC	0.006	0.053	-9999	-10000	0	0
calcium ion-dependent exocytosis	0.02	0.003	-9999	-10000	0	0
Dynamin 2/GTP	-0.034	0.091	-9999	-0.28	43	43
EXOC4	0.01	0	-9999	-10000	0	0
CD59	0.01	0.035	-9999	-10000	0	0
CPE	0.002	0.065	-9999	-0.32	14	14
CTNNB1	0.01	0	-9999	-10000	0	0
membrane fusion	0	0	-9999	-10000	0	0
CTNND1	-0.009	0.092	-9999	-0.26	43	43
DNM2	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.017	0.025	-9999	-10000	0	0
TSHR	-0.02	0.1	-9999	-0.32	37	37
INS	0.006	0.009	-9999	-10000	0	0
BIN1	0.01	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	-0.025	0.11	-9999	-0.32	43	43
membrane depolarization	0	0	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
mol:Ca2+	-0.034	0.091	-9999	-0.28	43	43
JUP	0.01	0.035	-9999	-10000	0	0
ASAP2/amphiphysin II	0	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
CDH1	0.009	0.038	-9999	-10000	0	0
clathrin-independent pinocytosis	0	0	-9999	-10000	0	0
MAPK8IP3	0.01	0	-9999	-10000	0	0
positive regulation of endocytosis	0	0	-9999	-10000	0	0
EXOC2	0.01	0	-9999	-10000	0	0
substrate adhesion-dependent cell spreading	0.034	0	-9999	-10000	0	0
insulin receptor binding	0	0	-9999	-10000	0	0
SPAG9	0.01	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.024	0.063	-9999	-10000	0	0
positive regulation of phagocytosis	0.015	0	-9999	-10000	0	0
ARF6/GTP/JIP3	0	0	-9999	-10000	0	0
ACAP1	0.02	0.01	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CHRM2	-0.033	0.093	-9999	-0.35	10	10
clathrin heavy chain/ACAP1	0.011	0.05	-9999	-10000	0	0
JIP4/KLC1	0	0	-9999	-10000	0	0
EXOC1	0.01	0	-9999	-10000	0	0
exocyst	0.034	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	-0.009	0.092	-9999	-0.26	43	43
NME1	-0.025	0.11	-9999	-0.32	43	43
clathrin coat assembly	0.006	0.053	-9999	-10000	0	0
IL2RA	-0.002	0.051	-9999	-0.22	3	3
VAMP3	0.015	0	-9999	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.017	0.047	-9999	-0.34	2	2
EXOC6	0.01	0	-9999	-10000	0	0
PLD1	0	0	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
EXOC5	0.01	0	-9999	-10000	0	0
PIP5K1C	0.017	0.025	-9999	-10000	0	0
SDC1	0.01	0.035	-9999	-10000	0	0
ARF6/GDP	-0.026	0.11	-9999	-0.31	43	43
EXOC7	0.01	0	-9999	-10000	0	0
E-cadherin/beta catenin	-0.025	0.065	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
endocytosis	0	0	-9999	-10000	0	0
SCAMP2	0.01	0	-9999	-10000	0	0
ADRB2	-0.086	0.14	-9999	-0.37	28	28
EXOC3	0.01	0	-9999	-10000	0	0
ASAP2	0.01	0	-9999	-10000	0	0
Dynamin 2/GDP	-0.017	0.097	-9999	-0.28	43	43
KLC1	0.01	0	-9999	-10000	0	0
AVPR2	-0.05	0.12	-9999	-0.37	15	15
RALA	0.01	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.022	0.058	-9999	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.017	0.063	-10000	0	-0.26	13	13
ER alpha/Gai/GDP/Gbeta gamma	0.003	0.094	-10000	0	-0.38	11	11
AKT1	0.005	0.12	-10000	0	-0.71	10	10
PIK3CA	0.01	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.002	0.13	-10000	0	-0.73	10	10
mol:Ca2+	0.01	0.096	-10000	0	-0.41	13	13
IGF1R	0.008	0.027	-10000	0	-0.5	1	1
E2/ER alpha (dimer)/Striatin	-0.019	0.075	-10000	0	-0.31	22	22
SHC1	0.01	0	-10000	0	-10000	0	0
apoptosis	-0.006	0.12	0.68	10	-10000	0	10
RhoA/GTP	-0.013	0.052	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.027	0.078	-10000	0	-0.38	12	12
regulation of stress fiber formation	-0.028	0.054	0.36	1	-10000	0	1
E2/ERA-ERB (dimer)	-0.02	0.076	-10000	0	-0.31	23	23
KRAS	0.01	0	-10000	0	-10000	0	0
G13/GTP	-0.017	0.068	-10000	0	-0.28	22	22
pseudopodium formation	0.028	0.054	-10000	0	-0.36	1	1
E2/ER alpha (dimer)/PELP1	-0.019	0.075	-10000	0	-0.31	22	22
GRB2	0.01	0	-10000	0	-10000	0	0
GNG2	0.008	0.027	-10000	0	-0.5	1	1
GNAO1	0.005	0.048	-10000	0	-0.51	3	3
HRAS	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.011	0.094	-10000	0	-0.45	10	10
E2/ER beta (dimer)	-0.001	0.02	-10000	0	-0.38	1	1
mol:GDP	-0.016	0.065	-10000	0	-0.35	10	10
mol:NADP	0.011	0.094	-10000	0	-0.45	10	10
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	0.01	0.1	-10000	0	-0.43	13	13
IGF-1R heterotetramer	0.008	0.027	-10000	0	-0.5	1	1
PLCB1	0.009	0.092	-10000	0	-0.44	12	12
PLCB2	0.004	0.1	-10000	0	-0.45	13	13
IGF1	0.002	0.061	-10000	0	-0.51	5	5
mol:L-citrulline	0.011	0.094	-10000	0	-0.45	10	10
RHOA	0.01	0	-10000	0	-10000	0	0
Gai/GDP	-0.022	0.08	-10000	0	-0.66	3	3
JNK cascade	-0.001	0.02	-10000	0	-0.38	1	1
BCAR1	0.008	0.027	-10000	0	-0.5	1	1
ESR2	0.008	0.028	-10000	0	-0.52	1	1
GNAQ	0.008	0.027	-10000	0	-0.5	1	1
ESR1	-0.023	0.13	-10000	0	-0.51	22	22
Gq family/GDP/Gbeta gamma	0.022	0.057	-10000	0	-0.46	2	2
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.017	0.051	-10000	0	-0.28	1	1
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.026	0.077	-10000	0	-0.38	11	11
GNAZ	-0.031	0.14	-10000	0	-0.5	28	28
E2/ER alpha (dimer)	-0.023	0.09	-10000	0	-0.37	22	22
STRN	0.01	0	-10000	0	-10000	0	0
GNAL	0.001	0.067	-10000	0	-0.51	6	6
PELP1	0.01	0	-10000	0	-10000	0	0
MAPK11	0.011	0.034	-10000	0	-0.3	4	4
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	0.007	0.039	-10000	0	-0.5	2	2
HBEGF	-0.024	0.11	-10000	0	-0.47	6	6
cAMP biosynthetic process	-0.02	0.071	-10000	0	-0.26	27	27
SRC	0.009	0.09	-10000	0	-0.58	2	2
PI3K	0	0	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.014	0.057	-10000	0	-0.3	10	10
SOS1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.024	0.07	-10000	0	-0.55	2	2
Gs family/GTP	-0.02	0.072	-10000	0	-0.26	27	27
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0	0	-10000	0	-10000	0	0
vasodilation	0.011	0.09	-10000	0	-0.43	10	10
mol:DAG	0.01	0.1	-10000	0	-0.43	13	13
Gs family/GDP/Gbeta gamma	-0.016	0.063	-10000	0	-0.33	10	10
MSN	0.029	0.057	-10000	0	-0.39	1	1
Gq family/GTP	-0.021	0.09	-10000	0	-0.47	12	12
mol:PI-3-4-5-P3	0.002	0.12	-10000	0	-0.7	10	10
NRAS	0.01	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.011	0.09	0.43	10	-10000	0	10
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.015	0.06	-10000	0	-0.33	10	10
NOS3	0.01	0.098	-10000	0	-0.47	10	10
GNA11	0.008	0.027	-10000	0	-0.5	1	1
MAPKKK cascade	0.019	0.1	-10000	0	-0.52	10	10
E2/ER alpha (dimer)/PELP1/Src	-0.028	0.081	-10000	0	-0.4	11	11
ruffle organization	0.028	0.054	-10000	0	-0.36	1	1
ROCK2	0.024	0.057	-10000	0	-10000	0	0
GNA14	-0.008	0.093	-10000	0	-0.5	12	12
GNA15	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
MMP9	-0.028	0.13	-10000	0	-0.51	6	6
MMP2	0.015	0.086	-10000	0	-0.54	2	2

×

Regulation of nuclear SMAD2/3 signaling

Figure S83. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S83. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.013	0.008	-10000	0	-10000	0	0
HSPA8	0.008	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.016	0.083	0.2	1	-0.32	21	22
AKT1	0.007	0.02	-10000	0	-10000	0	0
GSC	-0.025	0.11	-10000	0	-0.43	1	1
NKX2-5	-0.032	0.13	-10000	0	-0.52	25	25
muscle cell differentiation	0.02	0.056	0.33	2	-10000	0	2
SMAD2-3/SMAD4/SP1	0.041	0.057	-10000	0	-10000	0	0
SMAD4	0.018	0.023	-10000	0	-10000	0	0
CBFB	0.01	0	-10000	0	-10000	0	0
SAP18	0.009	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.012	0.078	-10000	0	-0.29	23	23
SMAD3/SMAD4/VDR	0.009	0.034	-10000	0	-0.32	1	1
MYC	0.01	0.044	-10000	0	-0.51	2	2
CDKN2B	-0.06	0.33	-10000	0	-1.3	25	25
AP1	0.024	0.084	-10000	0	-0.5	2	2
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.042	0.025	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.01	0.094	-10000	0	-0.31	21	21
SP3	0.012	0	-10000	0	-10000	0	0
CREB1	0.01	0	-10000	0	-10000	0	0
FOXH1	-0.05	0.17	-10000	0	-0.52	39	39
SMAD3/SMAD4/GR	0.003	0.022	-10000	0	-10000	0	0
GATA3	0.009	0.043	-10000	0	-0.51	2	2
SKI/SIN3/HDAC complex/NCoR1	0.032	0.015	-10000	0	-10000	0	0
MEF2C/TIF2	-0.044	0.1	-10000	0	-0.46	5	5
endothelial cell migration	-0.003	0.08	1.3	1	-10000	0	1
MAX	0.009	0.004	-10000	0	-10000	0	0
RBBP7	0.009	0.002	-10000	0	-10000	0	0
RBBP4	0.009	0.002	-10000	0	-10000	0	0
RUNX2	-0.001	0.074	-10000	0	-0.52	7	7
RUNX3	0.007	0.039	-10000	0	-0.5	2	2
RUNX1	0.01	0	-10000	0	-10000	0	0
CTBP1	0.01	0	-10000	0	-10000	0	0
NR3C1	0.009	0.004	-10000	0	-10000	0	0
VDR	0.007	0.039	-10000	0	-0.51	2	2
CDKN1A	0.048	0.076	-10000	0	-1.2	1	1
KAT2B	0.011	0.003	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.041	0.1	-10000	0	-0.32	39	39
DCP1A	0.01	0	-10000	0	-10000	0	0
SKI	0.009	0.002	-10000	0	-10000	0	0
SERPINE1	0.003	0.081	-10000	0	-1.3	1	1
SMAD3/SMAD4/ATF2	0.003	0.021	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.007	0.059	-10000	0	-0.3	12	12
SAP30	0.009	0.002	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.012	0.026	-10000	0	-10000	0	0
JUN	0.026	0.083	-10000	0	-0.5	2	2
SMAD3/SMAD4/IRF7	0.002	0.029	-10000	0	-0.31	1	1
TFE3	0.015	0.004	-10000	0	-10000	0	0
COL1A2	-0.011	0.1	-10000	0	-0.43	15	15
mesenchymal cell differentiation	0.004	0.051	0.33	7	-10000	0	7
DLX1	-0.022	0.12	-10000	0	-0.52	19	19
TCF3	0.01	0	-10000	0	-10000	0	0
FOS	-0.025	0.14	-10000	0	-0.5	27	27
SMAD3/SMAD4/Max	0.003	0.022	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.001	0.006	-10000	0	-10000	0	0
ZBTB17	0.012	0.015	-10000	0	-10000	0	0
LAMC1	0.043	0.026	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.003	0.021	-10000	0	-10000	0	0
IRF7	0.009	0.029	-10000	0	-0.52	1	1
ESR1	-0.023	0.13	-10000	0	-0.51	22	22
HNF4A	-0.1	0.22	-10000	0	-0.52	75	75
MEF2C	-0.015	0.12	-10000	0	-0.5	4	4
SMAD2-3/SMAD4	-0.006	0.026	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.008	0.018	-10000	0	-10000	0	0
IGHV3OR16-13	-0.001	0.006	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.01	0	-10000	0	-10000	0	0
CREBBP	0.012	0.005	-10000	0	-10000	0	0
SKIL	0.01	0	-10000	0	-10000	0	0
HDAC1	0.009	0.002	-10000	0	-10000	0	0
HDAC2	0.009	0.002	-10000	0	-10000	0	0
SNIP1	0.008	0.004	-10000	0	-10000	0	0
GCN5L2	0.002	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.005	0.023	-10000	0	-10000	0	0
MSG1/HSC70	-0.024	0.091	-10000	0	-0.36	24	24
SMAD2	0.007	0.021	-10000	0	-10000	0	0
SMAD3	0.019	0.021	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.036	0.025	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.016	0.012	-10000	0	-10000	0	0
NCOR1	0.009	0.002	-10000	0	-10000	0	0
NCOA2	0.007	0.039	-10000	0	-0.5	2	2
NCOA1	0.01	0	-10000	0	-10000	0	0
MYOD/E2A	-0.002	0.028	-10000	0	-0.37	2	2
SMAD2-3/SMAD4/SP1/MIZ-1	0.047	0.054	-10000	0	-10000	0	0
IFNB1	0.033	0.039	-10000	0	-0.44	1	1
SMAD3/SMAD4/MEF2C	-0.002	0.12	-10000	0	-0.49	4	4
CITED1	-0.026	0.13	-10000	0	-0.51	24	24
SMAD2-3/SMAD4/ARC105	-0.003	0.022	-10000	0	-10000	0	0
RBL1	0.01	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.017	0.13	-10000	0	-0.46	25	25
RUNX1-3/PEBPB2	-0.002	0.022	-10000	0	-0.29	2	2
SMAD7	0.048	0.094	-10000	0	-0.64	2	2
MYC/MIZ-1	0.009	0.047	-10000	0	-0.36	2	2
SMAD3/SMAD4	0.025	0.066	0.28	1	-0.38	1	2
IL10	0.034	0.076	-10000	0	-0.49	6	6
PIASy/HDAC complex	0.008	0.005	-10000	0	-10000	0	0
PIAS3	0.011	0.003	-10000	0	-10000	0	0
CDK2	0.012	0.005	-10000	0	-10000	0	0
IL5	0.034	0.044	-10000	0	-10000	0	0
CDK4	0.007	0.049	-10000	0	-0.52	3	3
PIAS4	0.008	0.005	-10000	0	-10000	0	0
ATF3	-0.008	0.093	-10000	0	-0.5	12	12
SMAD3/SMAD4/SP1	-0.002	0.034	-10000	0	-10000	0	0
FOXG1	-0.056	0.16	-10000	0	-0.52	39	39
FOXO3	0.015	0.026	-10000	0	-10000	0	0
FOXO1	0.015	0.025	-10000	0	-10000	0	0
FOXO4	0.015	0.025	-10000	0	-10000	0	0
heart looping	-0.015	0.12	-10000	0	-0.49	4	4
CEBPB	0.008	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.016	0.078	-10000	0	-0.33	19	19
MYOD1	-0.002	0.039	-10000	0	-0.52	2	2
SMAD3/SMAD4/HNF4	-0.065	0.13	-10000	0	-0.32	75	75
SMAD3/SMAD4/GATA3	-0.001	0.043	-10000	0	-0.35	1	1
SnoN/SIN3/HDAC complex/NCoR1	0.01	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.004	0.031	-10000	0	-0.32	2	2
SMAD3/SMAD4/SP1-3	0.003	0.031	-10000	0	-10000	0	0
MED15	0.01	0	-10000	0	-10000	0	0
SP1	0.012	0.022	-10000	0	-10000	0	0
SIN3B	0.009	0.002	-10000	0	-10000	0	0
SIN3A	0.009	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.053	0.12	-10000	0	-0.37	21	21
ITGB5	0.05	0.035	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.035	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.032	0.1	-10000	0	-0.31	40	40
AR	-0.049	0.16	-10000	0	-0.5	40	40
negative regulation of cell growth	0.038	0.04	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.001	0.033	-10000	0	-0.33	2	2
E2F5	0.005	0.049	-10000	0	-0.52	3	3
E2F4	0.01	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.029	0.082	-10000	0	-0.32	6	6
SMAD2-3/SMAD4/FOXO1-3a-4	0.023	0.094	-10000	0	-0.31	25	25
TFDP1	0.01	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.028	0.085	-10000	0	-0.51	2	2
SMAD3/SMAD4/RUNX2	-0.004	0.051	-10000	0	-0.33	7	7
TGIF2	0.01	0	-10000	0	-10000	0	0
TGIF1	0.01	0	-10000	0	-10000	0	0
ATF2	0.01	0	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.008	0.027	-9999	-0.5	1	1
SPHK1	0.005	0.049	-9999	-0.52	3	3
GNAI2	0.01	0	-9999	-10000	0	0
mol:S1P	0.016	0.021	-9999	-0.27	1	1
GNAO1	0.005	0.048	-9999	-0.51	3	3
mol:Sphinganine-1-P	0.014	0.041	-9999	-0.37	4	4
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.001	0.012	-9999	-10000	0	0
GNAI3	0.01	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0.008	0.028	-9999	-0.52	1	1
S1PR2	0.01	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.002	0.017	-9999	-0.23	1	1
S1PR5	-0.025	0.13	-9999	-0.5	24	24
S1PR4	-0.025	0.13	-9999	-0.5	24	24
GNAI1	0.007	0.039	-9999	-0.5	2	2
S1P/S1P5/G12	-0.019	0.065	-9999	-0.26	24	24
S1P/S1P3/Gq	0.019	0.062	-9999	-0.27	12	12
S1P/S1P4/Gi	-0.004	0.094	-9999	-0.44	4	4
GNAQ	0.008	0.027	-9999	-0.5	1	1
GNAZ	-0.031	0.14	-9999	-0.5	28	28
GNA14	-0.008	0.093	-9999	-0.5	12	12
GNA15	0.01	0	-9999	-10000	0	0
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
GNA11	0.008	0.027	-9999	-0.5	1	1
ABCC1	0.01	0	-9999	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.029	0.076	0.41	5	-10000	0	5
GNAI2	0.01	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.021	0.076	-10000	0	-0.3	24	24
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.005	0.048	-10000	0	-0.51	3	3
RhoA/GTP	-0.03	0.077	-10000	0	-0.42	5	5
negative regulation of cAMP metabolic process	-0.01	0.095	-10000	0	-0.45	5	5
GNAZ	-0.031	0.14	-10000	0	-0.5	28	28
GNAI3	0.01	0	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
S1PR5	-0.025	0.13	-10000	0	-0.5	24	24
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.01	0.096	-10000	0	-0.46	5	5
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
GNAI1	0.007	0.039	-10000	0	-0.5	2	2

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.021	-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	-0.006	0.071	0.6	1	-10000	0	1
IL27/IL27R/JAK1	-0.025	0.084	-10000	0	-1.1	1	1
TBX21	0.001	0.14	-10000	0	-0.5	17	17
IL12B	0.003	0.056	-10000	0	-0.52	4	4
IL12A	0.003	0.044	-10000	0	-0.37	5	5
IL6ST	-0.002	0.077	-10000	0	-0.51	8	8
IL27RA/JAK1	0.01	0.065	-10000	0	-1.2	1	1
IL27	-0.002	0.072	-10000	0	-0.51	7	7
TYK2	0.01	0.004	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.059	0.12	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.006	0.071	0.6	1	-10000	0	1
T cell proliferation during immune response	-0.006	0.071	0.6	1	-10000	0	1
MAPKKK cascade	0.006	0.071	-10000	0	-0.6	1	1
STAT3	0.01	0	-10000	0	-10000	0	0
STAT2	0.01	0	-10000	0	-10000	0	0
STAT1	0.01	0.002	-10000	0	-10000	0	0
IL12RB1	-0.007	0.089	-10000	0	-0.5	11	11
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.009	0.16	-10000	0	-0.45	32	32
IL27/IL27R/JAK2/TYK2	0.006	0.072	-10000	0	-0.61	1	1
positive regulation of T cell mediated cytotoxicity	0.006	0.071	-10000	0	-0.6	1	1
STAT1 (dimer)	-0.046	0.13	0.48	1	-0.7	5	6
JAK2	0.009	0.003	-10000	0	-10000	0	0
JAK1	0.01	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	0.011	0.068	-10000	0	-0.58	1	1
T cell proliferation	-0.044	0.12	-10000	0	-0.48	6	6
IL12/IL12R/TYK2/JAK2	0.008	0.077	-10000	0	-0.69	1	1
IL17A	-0.059	0.12	-10000	0	-10000	0	0
mast cell activation	-0.006	0.071	0.6	1	-10000	0	1
IFNG	0.001	0.025	-10000	0	-0.11	4	4
T cell differentiation	-0.003	0.005	-10000	0	-0.019	16	16
STAT3 (dimer)	0.011	0.068	-10000	0	-0.58	1	1
STAT5A (dimer)	0.01	0.074	-10000	0	-0.81	1	1
STAT4 (dimer)	0.011	0.068	-10000	0	-0.58	1	1
STAT4	0.01	0	-10000	0	-10000	0	0
T cell activation	-0.006	0.007	0.12	1	-10000	0	1
IL27R/JAK2/TYK2	-0.013	0.07	-10000	0	-1.1	1	1
GATA3	0.003	0.07	-10000	0	-1.2	1	1
IL18	0.001	0.056	-10000	0	-0.36	8	8
positive regulation of mast cell cytokine production	0.011	0.067	-10000	0	-0.56	1	1
IL27/EBI3	-0.003	0.056	-10000	0	-0.36	8	8
IL27RA	0.001	0.067	-10000	0	-1.2	1	1
IL6	-0.1	0.21	-10000	0	-0.5	76	76
STAT5A	0.008	0.027	-10000	0	-0.5	1	1
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.003	0.025	0.46	1	-10000	0	1
IL1B	-0.012	0.086	-10000	0	-0.36	20	20
EBI3	0.007	0.028	-10000	0	-0.51	1	1
TNF	-0.009	0.08	-10000	0	-0.36	17	17

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.051	0.16	-9999	-0.66	3	3
RAD9A	0.01	0	-9999	-10000	0	0
AP1	-0.03	0.099	-9999	-0.36	29	29
IFNAR2	0.009	0.005	-9999	-10000	0	0
AKT1	0.001	0.049	-9999	-0.22	7	7
ER alpha/Oestrogen	-0.023	0.091	-9999	-0.38	22	22
NFX1/SIN3/HDAC complex	0.029	0.018	-9999	-10000	0	0
EGF	-0.093	0.21	-9999	-0.52	67	67
SMG5	0.01	0	-9999	-10000	0	0
SMG6	0.01	0	-9999	-10000	0	0
SP3/HDAC2	0.011	0.009	-9999	-10000	0	0
TERT/c-Abl	-0.075	0.13	-9999	-0.62	3	3
SAP18	0.007	0.004	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.028	0.13	-9999	-0.51	24	24
WRN	0.01	0	-9999	-10000	0	0
SP1	0.009	0.006	-9999	-10000	0	0
SP3	0.008	0.005	-9999	-10000	0	0
TERF2IP	0.01	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.07	0.12	-9999	-0.56	3	3
Mad/Max	0	0	-9999	-10000	0	0
TERT	-0.053	0.17	-9999	-0.68	3	3
CCND1	-0.046	0.18	-9999	-0.99	4	4
MAX	0.008	0.005	-9999	-10000	0	0
RBBP7	0.007	0.004	-9999	-10000	0	0
RBBP4	0.007	0.004	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0.01	0	-9999	-10000	0	0
SIN3A	0.007	0.004	-9999	-10000	0	0
Telomerase/911	0.023	0.028	-9999	-10000	0	0
CDKN1B	-0.006	0.092	-9999	-0.31	7	7
RAD1	0.01	0	-9999	-10000	0	0
XRCC5	0.01	0	-9999	-10000	0	0
XRCC6	0.01	0	-9999	-10000	0	0
SAP30	0.007	0.004	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.008	0.005	-9999	-10000	0	0
JUN	0.005	0.039	-9999	-0.51	2	2
E6	-0.001	0.003	-9999	-10000	0	0
HPV-16 E6/E6AP	0.006	0.004	-9999	-10000	0	0
FOS	-0.031	0.14	-9999	-0.51	27	27
IFN-gamma/IRF1	-0.033	0.1	-9999	-0.36	32	32
PARP2	0.01	0	-9999	-10000	0	0
BLM	-0.051	0.17	-9999	-0.52	40	40
Telomerase	-0.016	0.055	-9999	-10000	0	0
IRF1	0.011	0.006	-9999	-10000	0	0
ESR1	-0.025	0.13	-9999	-0.52	22	22
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.032	0.019	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.032	0.019	-9999	-10000	0	0
HDAC1	0.007	0.004	-9999	-10000	0	0
HDAC2	0.009	0.005	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.019	0.004	-9999	-10000	0	0
ABL1	0.01	0	-9999	-10000	0	0
MXD1	0.008	0.005	-9999	-10000	0	0
MRE11A	0.01	0	-9999	-10000	0	0
HUS1	0.01	0	-9999	-10000	0	0
RPS6KB1	0.01	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.075	0.13	-9999	-0.61	3	3
NR2F2	0.009	0.009	-9999	-10000	0	0
MAPK3	0.012	0.008	-9999	-10000	0	0
MAPK1	0.012	0.008	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.01	0.002	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
HNRNPC	0.01	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	0.01	0	-9999	-10000	0	0
EGFR	-0.007	0.088	-9999	-0.52	10	10
mol:Oestrogen	-0.001	0.002	-9999	-10000	0	0
EGF/EGFR	-0.081	0.16	-9999	-0.38	75	75
MYC	0.005	0.039	-9999	-0.51	2	2
IL2	0.004	0.01	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
TGFB1	0.01	0.002	-9999	-10000	0	0
TRF2/BLM	-0.039	0.11	-9999	-0.34	40	40
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.073	0.13	-9999	-0.62	3	3
SP1/HDAC2	0.013	0.011	-9999	-10000	0	0
PINX1	0.01	0	-9999	-10000	0	0
Telomerase/EST1A	-0.07	0.12	-9999	-0.56	3	3
Smad3/Myc	0.009	0.026	-9999	-0.29	2	2
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.037	0.15	-9999	-0.51	32	32
Telomerase/PinX1	-0.07	0.12	-9999	-0.56	3	3
Telomerase/AKT1/mTOR/p70S6K	0.008	0.053	-9999	-10000	0	0
SIN3B	0.007	0.004	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
Telomerase/EST1B	-0.07	0.12	-9999	-0.56	3	3
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	-0.07	0.12	-9999	-0.56	3	3
E2F1	-0.001	0.07	-9999	-0.53	6	6
ZNFX1	0.007	0.004	-9999	-10000	0	0
PIF1	-0.054	0.17	-9999	-0.52	42	42
NCL	0.01	0	-9999	-10000	0	0
DKC1	0.01	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.008	0.027	-10000	0	-0.5	1	1
ANTXR2	0.01	0	-10000	0	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0.004	-10000	0	-0.066	1	1
monocyte activation	-0.009	0.1	-10000	0	-0.44	17	17
MAP2K2	0	0.001	-10000	0	-10000	0	0
MAP2K1	0	0.003	-10000	0	-10000	0	0
MAP2K7	0	0.003	-10000	0	-10000	0	0
MAP2K6	-0.009	0.049	-10000	0	-0.27	12	12
CYAA	0.012	0.014	-10000	0	-0.26	1	1
MAP2K4	0	0.003	-10000	0	-10000	0	0
IL1B	-0.002	0.066	-10000	0	-0.26	21	21
Channel	-0.001	0.015	-10000	0	-0.27	1	1
NLRP1	-0.002	0.02	-10000	0	-0.26	2	2
CALM1	0.01	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0	0.004	0.066	1	-10000	0	1
MAPK3	0	0.003	-10000	0	-10000	0	0
MAPK1	0	0.003	-10000	0	-10000	0	0
PGR	-0.04	0.094	-10000	0	-0.26	54	54
PA/Cellular Receptors	-0.001	0.016	-10000	0	-0.3	1	1
apoptosis	0	0.004	-10000	0	-0.066	1	1
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.001	0.014	-10000	0	-0.26	1	1
macrophage activation	0.016	0.003	-10000	0	-10000	0	0
TNF	-0.015	0.11	-10000	0	-0.5	17	17
VCAM1	-0.009	0.1	-10000	0	-0.45	17	17
platelet activation	0	0.004	-10000	0	-10000	0	0
MAPKKK cascade	-0.011	0.014	-10000	0	-10000	0	0
IL18	0.007	0.051	-10000	0	-0.31	8	8
negative regulation of macrophage activation	0	0.004	-10000	0	-0.066	1	1
LEF	0	0.004	-10000	0	-0.066	1	1
CASP1	-0.002	0.019	-10000	0	-0.23	2	2
mol:cAMP	0	0.004	-10000	0	-10000	0	0
necrosis	0	0.004	-10000	0	-0.066	1	1
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.001	0.014	-10000	0	-0.26	1	1
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0.001	-9999	-10000	0	0
HDAC2	0.01	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.004	0.036	-9999	-0.3	5	5
forebrain development	-0.015	0.15	-9999	-0.54	14	14
GNAO1	0.004	0.048	-9999	-0.51	3	3
SMO/beta Arrestin2	0.01	0.041	-9999	-0.37	4	4
SMO	0.003	0.056	-9999	-0.52	4	4
ARRB2	0.009	0.004	-9999	-10000	0	0
GLI3/SPOP	0.035	0.035	-9999	-10000	0	0
mol:GTP	0	0.003	-9999	-10000	0	0
GSK3B	0.01	0	-9999	-10000	0	0
GNAI2	0.009	0.004	-9999	-10000	0	0
SIN3/HDAC complex	0.005	0.012	-9999	-10000	0	0
GNAI1	0.006	0.039	-9999	-0.51	2	2
XPO1	0.01	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.047	0.11	-9999	-0.6	7	7
SAP30	0.01	0.001	-9999	-10000	0	0
mol:GDP	0.003	0.056	-9999	-0.52	4	4
MIM/GLI2A	0.003	0.043	-9999	-0.53	1	1
IFT88	0.01	0	-9999	-10000	0	0
GNAI3	0.009	0.004	-9999	-10000	0	0
GLI2	0.036	0.014	-9999	-10000	0	0
GLI3	0.031	0.037	-9999	-0.24	6	6
CSNK1D	0.01	0	-9999	-10000	0	0
CSNK1E	0.01	0	-9999	-10000	0	0
SAP18	0.01	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.01	0	-9999	-10000	0	0
GNG2	0.008	0.027	-9999	-0.5	1	1
Gi family/GTP	0.001	0.083	-9999	-0.28	17	17
SIN3B	0.01	0.001	-9999	-10000	0	0
SIN3A	0.01	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.037	0.033	-9999	-10000	0	0
GLI2/Su(fu)	0.04	0.029	-9999	-10000	0	0
FOXA2	-0.18	0.39	-9999	-1	60	60
neural tube patterning	-0.015	0.15	-9999	-0.54	14	14
SPOP	0.01	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.02	0.019	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
CSNK1G2	0.01	0	-9999	-10000	0	0
CSNK1G3	0.01	0	-9999	-10000	0	0
MTSS1	0.003	0.043	-9999	-0.53	1	1
embryonic limb morphogenesis	-0.015	0.15	-9999	-0.54	14	14
SUFU	0.019	0.021	-9999	-10000	0	0
LGALS3	0.01	0	-9999	-10000	0	0
catabolic process	0.055	0.034	-9999	-0.3	1	1
GLI3A/CBP	0.002	0.062	-9999	-0.33	11	11
KIF3A	0.01	0	-9999	-10000	0	0
GLI1	-0.016	0.15	-9999	-0.55	14	14
RAB23	0.01	0	-9999	-10000	0	0
CSNK1A1	0.01	0	-9999	-10000	0	0
IFT172	0.01	0	-9999	-10000	0	0
RBBP7	0.01	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	0.02	0.019	-9999	-10000	0	0
GNAZ	-0.032	0.14	-9999	-0.51	28	28
RBBP4	0.01	0.001	-9999	-10000	0	0
CSNK1G1	0.01	0	-9999	-10000	0	0
PIAS1	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GLI2/SPOP	0.038	0.013	-9999	-10000	0	0
STK36	0.01	0.005	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.008	0.076	-9999	-0.5	2	2
PTCH1	-0.011	0.16	-9999	-0.86	7	7
MIM/GLI1	-0.047	0.22	-9999	-0.5	63	63
CREBBP	0.003	0.062	-9999	-0.33	11	11
Su(fu)/SIN3/HDAC complex	0.04	0.007	-9999	-10000	0	0

×

FoxO family signaling

Figure S90. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S90. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.015	0.051	-9999	-10000	0	0
PLK1	-0.14	0.26	-9999	-0.61	35	35
CDKN1B	0.005	0.12	-9999	-10000	0	0
FOXO3	-0.09	0.22	-9999	-0.52	35	35
KAT2B	0.002	0.019	-9999	-10000	0	0
FOXO1/SIRT1	0.014	0.031	-9999	-10000	0	0
CAT	-0.084	0.23	-9999	-1.2	5	5
CTNNB1	0.01	0	-9999	-10000	0	0
AKT1	0.003	0.021	-9999	-10000	0	0
FOXO1	0.02	0.031	-9999	-10000	0	0
MAPK10	-0.006	0.089	-9999	-0.26	39	39
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.05	0.067	-9999	-10000	0	0
response to oxidative stress	-0.01	0.024	-9999	-10000	0	0
FOXO3A/SIRT1	-0.13	0.16	-9999	-0.48	34	34
XPO1	0.01	0	-9999	-10000	0	0
EP300	0.01	0.004	-9999	-10000	0	0
BCL2L11	0.006	0.032	-9999	-10000	0	0
FOXO1/SKP2	0.019	0.042	-9999	-0.28	3	3
mol:GDP	-0.01	0.024	-9999	-10000	0	0
RAN	0.008	0.04	-9999	-0.52	2	2
GADD45A	-0.001	0.12	-9999	-0.72	2	2
YWHAQ	0.01	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.054	0.018	-9999	-10000	0	0
MST1	-0.016	0.099	-9999	-0.53	12	12
CSNK1D	0.01	0	-9999	-10000	0	0
CSNK1E	0.01	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.041	0.024	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
MAPK8	0.024	0.01	-9999	-10000	0	0
MAPK9	0.024	0.01	-9999	-10000	0	0
YWHAG	0.01	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
YWHAZ	0.01	0	-9999	-10000	0	0
SIRT1	0.008	0.009	-9999	-10000	0	0
SOD2	0.001	0.14	-9999	-10000	0	0
RBL2	-0.035	0.16	-9999	-0.49	4	4
RAL/GDP	0.012	0.014	-9999	-10000	0	0
CHUK	0.002	0.02	-9999	-10000	0	0
Ran/GTP	0.008	0.029	-9999	-0.38	2	2
CSNK1G2	0.01	0	-9999	-10000	0	0
RAL/GTP	0.018	0.016	-9999	-10000	0	0
CSNK1G1	0.01	0	-9999	-10000	0	0
FASLG	-0.012	0.16	-9999	-1.3	5	5
SKP2	0.004	0.056	-9999	-0.52	4	4
USP7	0.011	0.001	-9999	-10000	0	0
IKBKB	0.002	0.02	-9999	-10000	0	0
CCNB1	-0.12	0.26	-9999	-0.6	35	35
FOXO1-3a-4/beta catenin	-0.042	0.075	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.042	-9999	-0.28	3	3
CSNK1A1	0.01	0	-9999	-10000	0	0
SGK1	0.001	0.034	-9999	-0.53	1	1
CSNK1G3	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.017	0.025	-9999	-0.31	2	2
ZFAND5	0.053	0.059	-9999	-10000	0	0
SFN	-0.002	0.079	-9999	-0.52	8	8
CDK2	0.01	0.006	-9999	-10000	0	0
FOXO3A/14-3-3	0.018	0.049	-9999	-0.37	1	1
CREBBP	0.01	0.006	-9999	-10000	0	0
FBXO32	-0.096	0.23	-9999	-0.59	33	33
BCL6	-0.035	0.16	-9999	-0.49	4	4
RALB	0.011	0	-9999	-10000	0	0
RALA	0.011	0	-9999	-10000	0	0
YWHAH	0.01	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	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.024	0	-9999	-10000	0	0
SNTA1	0.007	0.04	-9999	-0.52	2	2
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.02	0.035	-9999	-0.31	4	4
MAPK12	0.014	0.055	-9999	-0.27	12	12
CCND1	0.01	0.044	-9999	-0.4	3	3
p38 gamma/SNTA1	0.016	0.055	-9999	-10000	0	0
MAP2K3	0.01	0	-9999	-10000	0	0
PKN1	0.01	0	-9999	-10000	0	0
G2/M transition checkpoint	0.014	0.055	-9999	-0.27	12	12
MAP2K6	0.008	0.06	-9999	-0.3	13	13
MAPT	0.007	0.071	-9999	-0.29	17	17
MAPK13	0.018	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.013	0.017	-9999	-0.32	1	1

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0	-10000	0	-10000	0	0
HDAC3	0.01	0	-10000	0	-10000	0	0
VDR	0.007	0.039	-10000	0	-0.51	2	2
Cbp/p300/PCAF	0	0	-10000	0	-10000	0	0
EP300	0.01	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.033	0.02	-10000	0	-10000	0	0
KAT2B	0.01	0	-10000	0	-10000	0	0
MAPK14	0.01	0	-10000	0	-10000	0	0
AKT1	0.017	0.028	0.2	1	-0.23	2	3
RAR alpha/9cRA/Cyclin H	-0.005	0.024	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.031	0.021	-10000	0	-10000	0	0
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.007	0.026	-10000	0	-10000	0	0
NCOR2	0.01	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.028	-10000	0	-0.37	2	2
RXRs/RARs/NRIP1/9cRA	-0.008	0.071	-10000	0	-0.55	2	2
NCOA2	0.007	0.039	-10000	0	-0.5	2	2
NCOA3	0.01	0	-10000	0	-10000	0	0
NCOA1	0.01	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.007	0.039	-10000	0	-0.51	2	2
RARG	0.01	0	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0.01	0	-10000	0	-10000	0	0
MAPK1	0.01	0	-10000	0	-10000	0	0
MAPK8	0.011	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.041	0.061	-10000	0	-0.5	3	3
RARA	0.014	0.037	-10000	0	-0.23	2	2
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.029	0.026	-10000	0	-10000	0	0
PRKCA	0.01	0.039	-10000	0	-0.5	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.021	0.079	-10000	0	-0.59	2	2
RXRG	-0.16	0.18	-10000	0	-0.33	177	177
RXRA	0.02	0.035	-10000	0	-0.23	2	2
RXRB	0.008	0.055	-10000	0	-0.31	2	2
VDR/Vit D3/DNA	-0.002	0.028	-10000	0	-0.37	2	2
RBP1	0.002	0.062	-10000	0	-0.52	5	5
CRBP1/9-cic-RA	-0.005	0.044	-10000	0	-0.38	5	5
RARB	0.009	0.039	-10000	0	-0.5	2	2
PRKCG	-0.023	0.13	-10000	0	-0.52	22	22
MNAT1	0.01	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.009	0.07	-10000	0	-0.59	2	2
RXRs/RARs/SMRT(N-CoR2)/9cRA	0	0.061	-10000	0	-0.45	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.032	0.028	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.021	0.079	-10000	0	-0.59	2	2
positive regulation of DNA binding	-0.005	0.023	-10000	0	-10000	0	0
NRIP1	-0.02	0.074	-10000	0	-0.54	2	2
RXRs/RARs	-0.029	0.08	-10000	0	-0.5	3	3
RXRs/RXRs/DNA/9cRA	-0.044	0.062	-10000	0	-0.62	2	2
PRKACA	0.01	0	-10000	0	-10000	0	0
CDK7	0.01	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.004	0.015	-10000	0	-10000	0	0
CCNH	0.01	0	-10000	0	-10000	0	0
CREBBP	0.01	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

Insulin Pathway

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
CBL/APS/CAP	-0.013	0.052	-9999	-10000	0	0
TC10/GTP	-0.012	0.049	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	-0.001	0.014	-9999	-10000	0	0
HRAS	0.01	0	-9999	-10000	0	0
APS homodimer	0.008	0.027	-9999	-0.5	1	1
GRB14	-0.029	0.14	-9999	-0.52	26	26
FOXO3	-0.004	0.029	-9999	-0.52	1	1
AKT1	0.023	0.065	-9999	-10000	0	0
INSR	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.01	0	-9999	-10000	0	0
SORBS1	-0.018	0.12	-9999	-0.5	19	19
CRK	0.01	0	-9999	-10000	0	0
PTPN1	0.028	0	-9999	-10000	0	0
CAV1	-0.15	0.14	-9999	-0.26	214	214
CBL/APS/CAP/Crk-II/C3G	-0.013	0.055	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	-0.001	0.014	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.012	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.03	0.011	-9999	-10000	0	0
RPS6KB1	0.028	0.061	-9999	-10000	0	0
PARD6A	0.008	0.027	-9999	-0.5	1	1
CBL	0.01	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.013	0.047	-9999	-10000	0	0
HRAS/GTP	-0.002	0.018	-9999	-10000	0	0
Insulin Receptor	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.001	0.013	-9999	-10000	0	0
PRKCI	-0.004	0.014	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.017	0.058	-9999	-10000	0	0
SHC1	0.01	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PI3K	-0.001	0.012	-9999	-10000	0	0
NCK2	0.01	0	-9999	-10000	0	0
RHOQ	0.01	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
AKT2	0.023	0.065	-9999	-10000	0	0
PRKCZ	-0.007	0.036	-9999	-0.45	2	2
SH2B2	0.008	0.027	-9999	-0.5	1	1
SHC/SHIP	0.024	0.024	-9999	-10000	0	0
F2RL2	-0.038	0.15	-9999	-0.52	32	32
TRIP10	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.015	0.06	-9999	-0.26	20	20
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0	-9999	-10000	0	0
INPP5D	0.019	0.025	-9999	-10000	0	0
SOS1	0.01	0	-9999	-10000	0	0
SGK1	-0.003	0.042	-9999	-0.79	1	1
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
IRS1	0.008	0.027	-9999	-0.5	1	1
p62DOK/RasGAP	0	0	-9999	-10000	0	0
INS	0.003	0	-9999	-10000	0	0
mol:PI-3-4-P2	0.019	0.025	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
EIF4EBP1	0.02	0.076	-9999	-0.42	1	1
PTPRA	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.026	0.013	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.001	0.015	-9999	-0.28	1	1
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.024	0.074	-9999	-10000	0	0

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.025	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0	0	-9999	-10000	0	0
mol:DAG	0.019	0.06	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0	0	-9999	-10000	0	0
CaM/Ca2+	0.023	0.056	-9999	-10000	0	0
HIF1A	0.016	0	-9999	-10000	0	0
GAB1	0.008	0.027	-9999	-0.5	1	1
AKT1	0.037	0.047	-9999	-10000	0	0
PLCG1	0.019	0.06	-9999	-10000	0	0
NOS3	0.037	0.056	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
mol:NO	0.037	0.054	-9999	-10000	0	0
FLT1	0.024	0	-9999	-10000	0	0
PGF	-0.013	0.11	-9999	-0.52	15	15
VEGFR1 homodimer/NRP2/VEGFR121	-0.001	0.019	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
eNOS/Hsp90	0.041	0.053	-9999	-10000	0	0
endothelial cell proliferation	0.03	0.061	-9999	-0.38	3	3
mol:Ca2+	0.019	0.06	-9999	-10000	0	0
MAPK3	0.029	0.059	-9999	-0.47	1	1
MAPK1	0.029	0.059	-9999	-0.47	1	1
PIK3R1	0.01	0	-9999	-10000	0	0
PLGF homodimer	-0.013	0.11	-9999	-0.52	15	15
PRKACA	0.01	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.3	0.25	-9999	-0.5	214	214
VEGFA homodimer	0.01	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.025	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.034	0.058	-9999	-0.45	1	1
PI3K	-0.01	0.049	-9999	-10000	0	0
PRKCA	0.024	0.062	-9999	-0.5	1	1
PRKCB	0.021	0.071	-9999	-0.5	2	2
VEGFR1 homodimer/PLGF homodimer	0.011	0.066	-9999	-10000	0	0
VEGFA	0.01	0	-9999	-10000	0	0
VEGFB	0.01	0	-9999	-10000	0	0
mol:IP3	0.019	0.06	-9999	-10000	0	0
RASA1	0.032	0	-9999	-10000	0	0
NRP2	0.007	0.039	-9999	-0.5	2	2
VEGFR1 homodimer	0.024	0	-9999	-10000	0	0
VEGFB homodimer	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.1	0.13	-9999	-0.41	11	11
PTPN11	0.01	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.01	0.049	-9999	-10000	0	0
mol:L-citrulline	0.037	0.054	-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	0.01	0	-9999	-10000	0	0
PI3K/GAB1	-0.01	0.047	-9999	-10000	0	0
PDPK1	0.029	0.053	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0	0	-9999	-10000	0	0
mol:NADP	0.037	0.054	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	0.024	0.024	-9999	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0	0	-10000	0	-10000	0	0
TRAF2/ASK1	0	0	-10000	0	-10000	0	0
ATM	0.01	0	-10000	0	-10000	0	0
MAP2K3	0.022	0.026	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.027	0.029	-10000	0	-10000	0	0
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.004	0.055	-10000	0	-0.51	4	4
TXN	0.006	0.015	-10000	0	-0.2	2	2
CALM1	0.01	0	-10000	0	-10000	0	0
GADD45A	0.007	0.039	-10000	0	-0.51	2	2
GADD45B	0.005	0.047	-10000	0	-0.5	3	3
MAP3K1	0.01	0	-10000	0	-10000	0	0
MAP3K6	0.01	0	-10000	0	-10000	0	0
MAP3K7	0.01	0	-10000	0	-10000	0	0
MAP3K4	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0	0	-10000	0	-10000	0	0
TAK1/TAB family	0.001	0.015	0.17	3	-10000	0	3
RAC1/OSM/MEKK3	-0.001	0.014	-10000	0	-0.27	1	1
TRAF2	0.01	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.003	0.01	-10000	0	-10000	0	0
TRAF6	0.007	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.077	0.2	-10000	0	-0.52	57	57
CCM2	0.01	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.051	0.12	-10000	0	-0.32	57	57
MAPK11	0.005	0.047	-10000	0	-0.5	3	3
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.045	0.1	-10000	0	-0.28	57	57
OSM/MEKK3	-0.001	0.019	-10000	0	-0.36	1	1
TAOK1	0.014	0	-10000	0	-10000	0	0
TAOK2	0.014	0	-10000	0	-10000	0	0
TAOK3	0.014	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.01	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.01	0	-10000	0	-10000	0	0
MAP3K10	0.005	0.047	-10000	0	-0.5	3	3
MAP3K3	0.008	0.027	-10000	0	-0.5	1	1
TRX/ASK1	0.011	0.013	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	-0.006	0.043	-10000	0	-0.28	8	8

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.017	0.11	-9999	-0.53	3	3
MAP3K8	0.006	0.039	-9999	-0.5	2	2
FOS	0.021	0.071	-9999	-0.36	4	4
PRKCA	0.007	0.039	-9999	-0.51	2	2
PTPN7	0.011	0.003	-9999	-10000	0	0
HRAS	0.01	0.001	-9999	-10000	0	0
PRKCB	0.001	0.067	-9999	-0.51	6	6
NRAS	0.01	0.001	-9999	-10000	0	0
RAS family/GTP	0	0	-9999	-10000	0	0
MAPK3	0.02	0.04	-9999	-10000	0	0
MAP2K1	0.019	0.074	-9999	-0.43	8	8
ELK1	0.009	0.006	-9999	-10000	0	0
BRAF	-0.011	0.059	-9999	-0.4	8	8
mol:GTP	0	0.001	-9999	-0.005	27	27
MAPK1	0.02	0.04	-9999	-10000	0	0
RAF1	-0.011	0.059	-9999	-0.4	8	8
KRAS	0.01	0.001	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	-0.001	0.014	-9999	-0.26	1	1
HDAC3	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.002	0.021	-9999	-0.23	3	3
GATA1/HDAC4	-0.037	0.11	-9999	-0.36	37	37
GATA1/HDAC5	-0.036	0.11	-9999	-0.36	36	36
GATA2/HDAC5	-0.032	0.1	-9999	-0.36	32	32
HDAC5/BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC9	-0.002	0.078	-9999	-0.52	8	8
Glucocorticoid receptor/Hsp90/HDAC6	-0.001	0.016	-9999	-0.31	1	1
HDAC4/ANKRA2	-0.001	0.02	-9999	-0.37	1	1
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
GATA2	-0.037	0.15	-9999	-0.5	32	32
HDAC4/RFXANK	-0.001	0.02	-9999	-0.37	1	1
BCOR	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.008	0.027	-9999	-0.5	1	1
HDAC5	0.01	0	-9999	-10000	0	0
GNB1/GNG2	-0.001	0.019	-9999	-0.36	1	1
Histones	0.027	0.028	-9999	-10000	0	0
ADRBK1	0.01	0	-9999	-10000	0	0
HDAC4	0.008	0.028	-9999	-0.52	1	1
XPO1	0.01	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	-0.001	0.02	-9999	-0.37	1	1
HDAC7	0.01	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0.01	0	-9999	-10000	0	0
HDAC6	0.008	0.028	-9999	-0.52	1	1
HDAC5/RFXANK	0	0	-9999	-10000	0	0
CAMK4	0.004	0.055	-9999	-0.51	4	4
Tubulin/HDAC6	-0.007	0.046	-9999	-0.31	8	8
SUMO1	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
GATA1	-0.044	0.16	-9999	-0.5	36	36
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
NR3C1	0.01	0	-9999	-10000	0	0
SUMO1/HDAC4	-0.001	0.013	-9999	-0.25	1	1
SRF	0.01	0	-9999	-10000	0	0
HDAC4/YWHAB	-0.001	0.02	-9999	-0.37	1	1
Tubulin	-0.007	0.052	-9999	-0.37	7	7
HDAC4/14-3-3 E	-0.001	0.02	-9999	-0.37	1	1
GNB1	0.01	0	-9999	-10000	0	0
RANGAP1	0.01	0	-9999	-10000	0	0
BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	-0.001	0.016	-9999	-0.31	1	1
HDAC4/SRF	-0.004	0.035	-9999	-0.3	5	5
HDAC4/ER alpha	-0.024	0.09	-9999	-0.36	23	23
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.027	0.028	-9999	-10000	0	0
cell motility	-0.007	0.046	-9999	-0.31	8	8
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.01	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.008	0.028	-9999	-0.52	1	1
Hsp90/HDAC6	-0.001	0.02	-9999	-0.37	1	1
ESR1	-0.023	0.13	-9999	-0.51	22	22
HDAC6/HDAC11	-0.001	0.02	-9999	-0.37	1	1
Ran/GTP/Exportin 1	-0.001	0.017	-9999	-0.23	2	2
NPC	0	0	-9999	-10000	0	0
MEF2C	0.01	0	-9999	-10000	0	0
RAN	0.007	0.04	-9999	-0.52	2	2
HDAC4/MEF2C	-0.001	0.013	-9999	-10000	0	0
GNG2	0.008	0.027	-9999	-0.5	1	1
NCOR2	0.01	0	-9999	-10000	0	0
TUBB2A	-0.001	0.074	-9999	-0.52	7	7
HDAC11	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
ANKRA2	0.01	0	-9999	-10000	0	0
RFXANK	0.01	0	-9999	-10000	0	0
nuclear import	0.001	0.01	-9999	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.025	0.083	-10000	0	-0.51	4	4
CLOCK	0.012	0.003	-10000	0	-10000	0	0
TIMELESS/CRY2	0.029	0.039	-10000	0	-10000	0	0
DEC1/BMAL1	0	0.001	-10000	0	-10000	0	0
ATR	0.01	0	-10000	0	-10000	0	0
NR1D1	0.031	0.022	-10000	0	-10000	0	0
ARNTL	0.012	0.003	-10000	0	-10000	0	0
TIMELESS	0.029	0.044	-10000	0	-10000	0	0
NPAS2	0.009	0.04	-10000	0	-0.52	2	2
CRY2	0.01	0	-10000	0	-10000	0	0
mol:CO	-0.01	0.01	0.065	6	-10000	0	6
CHEK1	-0.037	0.15	-10000	0	-0.52	31	31
mol:HEME	0.01	0.01	-10000	0	-0.065	6	6
PER1	-0.012	0.1	-10000	0	-0.5	15	15
BMAL/CLOCK/NPAS2	0.031	0.026	-10000	0	-0.3	2	2
BMAL1/CLOCK	0.033	0.037	-10000	0	-10000	0	0
S phase of mitotic cell cycle	-0.025	0.083	-10000	0	-0.51	4	4
TIMELESS/CHEK1/ATR	-0.025	0.084	-10000	0	-0.51	4	4
mol:NADPH	0.01	0.01	-10000	0	-0.065	6	6
PER1/TIMELESS	0.018	0.072	-10000	0	-0.53	1	1
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.002	0.004	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.013	0.077	-9999	-0.59	4	4
MAP4K1	0.002	0.061	-9999	-0.5	5	5
MAP3K8	0.007	0.039	-9999	-0.5	2	2
PRKCB	0.001	0.066	-9999	-0.5	6	6
DBNL	0.01	0	-9999	-10000	0	0
CRKL	0.01	0	-9999	-10000	0	0
MAP3K1	0.025	0.072	-9999	-0.62	3	3
JUN	0.017	0.092	-9999	-0.64	6	6
MAP3K7	0.025	0.072	-9999	-0.62	3	3
GRAP2	-0.005	0.085	-9999	-0.5	10	10
CRK	0.01	0	-9999	-10000	0	0
MAP2K4	0.031	0.079	-9999	-0.72	3	3
LAT	0.008	0.028	-9999	-0.52	1	1
LCP2	0.007	0.039	-9999	-0.5	2	2
MAPK8	0.013	0.095	-9999	-0.68	6	6
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.02	0.076	-9999	-0.66	3	3
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.012	0.073	-9999	-0.66	3	3

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.03	0.013	-10000	0	-10000	0	0
regulation of axonogenesis	-0.023	0.004	-10000	0	-10000	0	0
myoblast fusion	0	0.011	-10000	0	-10000	0	0
mol:GTP	0	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.016	0.11	0.3	47	-10000	0	47
ARF1/GTP	0	0.002	-10000	0	-10000	0	0
mol:GM1	0.008	0.003	-10000	0	-10000	0	0
mol:Choline	0.023	0.003	-10000	0	-10000	0	0
lamellipodium assembly	0.011	0.032	-10000	0	-10000	0	0
MAPK3	0.02	0.008	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.016	0.11	-10000	0	-0.3	47	47
ARF1	0.01	0	-10000	0	-10000	0	0
ARF6/GDP	0	0.011	-10000	0	-10000	0	0
ARF1/GDP	0.027	0.018	-10000	0	-10000	0	0
ARF6	0.009	0.002	-10000	0	-10000	0	0
RAB11A	0.01	0	-10000	0	-10000	0	0
TIAM1	0.003	0.066	-10000	0	-0.5	6	6
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.02	0.008	-10000	0	-10000	0	0
actin filament bundle formation	0.001	0.006	-10000	0	-10000	0	0
KALRN	0.006	0.033	-10000	0	-0.26	3	3
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.001	0.006	-10000	0	-10000	0	0
NME1	-0.054	0.17	-10000	0	-0.52	43	43
Rac1/GDP	-0.001	0.006	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0	0.003	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.011	0.032	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
liver development	0	0.003	-10000	0	-10000	0	0
ARF6/GTP	0	0.003	-10000	0	-10000	0	0
RhoA/GTP	0	0.002	-10000	0	-10000	0	0
mol:GDP	0.009	0.027	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0	0.001	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
PLD1	0.016	0.004	-10000	0	-10000	0	0
RAB11FIP3	0.01	0	-10000	0	-10000	0	0
tube morphogenesis	0.011	0.032	-10000	0	-10000	0	0
ruffle organization	0.023	0.004	-10000	0	-10000	0	0
regulation of epithelial cell migration	0	0.003	-10000	0	-10000	0	0
PLD2	0.016	0.004	-10000	0	-10000	0	0
PIP5K1A	0.023	0.004	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.023	0.003	-10000	0	-10000	0	0
Rac1/GTP	0.012	0.032	-10000	0	-10000	0	0

×

IFN-gamma pathway

Figure S101. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S101. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.019	0.061	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0.01	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.015	0.046	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.003	0.01	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.013	0.038	-9999	-0.26	2	2
CaM/Ca2+	-0.018	0.056	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0.016	0.067	-9999	-10000	0	0
AKT1	0.025	0.061	-9999	-10000	0	0
MAP2K1	0.023	0.065	-9999	-10000	0	0
MAP3K11	0.015	0.068	-9999	-10000	0	0
IFNGR1	0.009	0.007	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.054	0.11	-9999	-0.37	34	34
Rap1/GTP	-0.013	0.041	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.021	0.067	-9999	-10000	0	0
CEBPB	0.045	0.082	-9999	-0.48	2	2
STAT3	0.01	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.019	0.059	-9999	-10000	0	0
STAT1	0.016	0.067	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.037	0.15	-9999	-0.52	32	32
PIK3CA	0.01	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	-0.014	0.053	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	-0.01	0.038	-9999	-0.34	1	1
mol:Ca2+	-0.019	0.061	-9999	-10000	0	0
MAPK3	0.033	0.061	-9999	-10000	0	0
STAT1 (dimer)	-0.016	0.05	-9999	-0.4	1	1
MAPK1	0.033	0.061	-9999	-10000	0	0
JAK2	0.009	0.007	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
JAK1	0.009	0.007	-9999	-10000	0	0
CAMK2D	0.01	0	-9999	-10000	0	0
DAPK1	0.04	0.093	-9999	-0.6	6	6
SMAD7	0.028	0.04	-9999	-0.26	1	1
CBL/CRKL/C3G	-0.016	0.049	-9999	-10000	0	0
PI3K	-0.017	0.053	-9999	-10000	0	0
IFNG	-0.037	0.15	-9999	-0.52	32	32
apoptosis	0.029	0.07	-9999	-0.43	6	6
CAMK2G	0.01	0	-9999	-10000	0	0
STAT3 (dimer)	0.01	0	-9999	-10000	0	0
CAMK2A	-0.041	0.15	-9999	-0.5	35	35
CAMK2B	-0.076	0.2	-9999	-0.52	57	57
FRAP1	0.026	0.058	-9999	-10000	0	0
PRKCD	0.027	0.062	-9999	-10000	0	0
RAP1B	0.01	0	-9999	-10000	0	0
negative regulation of cell growth	-0.013	0.038	-9999	-0.26	2	2
PTPN2	0.01	0	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
IRF1	0.047	0.054	-9999	-10000	0	0
STAT1 (dimer)/PIASy	-0.017	0.053	-9999	-10000	0	0
SOCS1	0.003	0.007	-9999	-10000	0	0
mol:GDP	-0.015	0.048	-9999	-10000	0	0
CASP1	0.028	0.043	-9999	-0.29	2	2
PTGES2	0.01	0	-9999	-10000	0	0
IRF9	0.041	0.029	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.016	0.052	-9999	-10000	0	0
RAP1/GDP	-0.013	0.041	-9999	-10000	0	0
CBL	0.015	0.067	-9999	-10000	0	0
MAP3K1	0.016	0.067	-9999	-10000	0	0
PIAS1	0.01	0	-9999	-10000	0	0
PIAS4	0.009	0	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.013	0.038	-9999	-0.26	2	2
PTPN11	0.009	0.07	-9999	-10000	0	0
CREBBP	0.01	0	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.009	0.059	-10000	0	-0.36	9	9
MAP4K4	0.027	0.047	-10000	0	-10000	0	0
BAG4	0.01	0	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.011	0.032	-10000	0	-0.24	1	1
NFKBIA	0.01	0	-10000	0	-10000	0	0
BIRC3	0.001	0.068	-10000	0	-0.52	6	6
BAX	-0.002	0.016	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
AKT1	0.017	0.007	-10000	0	-10000	0	0
BAD	-0.009	0.032	0.14	4	-10000	0	4
SMPD1	0.015	0.04	-10000	0	-0.16	16	16
RB1	-0.009	0.032	0.14	4	-10000	0	4
FADD/Caspase 8	0.034	0.045	-10000	0	-10000	0	0
MAP2K4	-0.003	0.03	-10000	0	-10000	0	0
NSMAF	0.01	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.003	0.03	-10000	0	-10000	0	0
EGF	-0.091	0.21	-10000	0	-0.52	67	67
mol:ceramide	-0.017	0.034	0.14	4	-10000	0	4
MADD	0.01	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.009	0.059	-10000	0	-0.36	9	9
ASAH1	0.008	0.027	-10000	0	-0.5	1	1
negative regulation of cell cycle	-0.009	0.032	0.14	4	-10000	0	4
cell proliferation	-0.008	0.024	-10000	0	-10000	0	0
BID	0.018	0.036	-10000	0	-10000	0	0
MAP3K1	-0.009	0.032	-10000	0	-10000	0	0
EIF2A	0.003	0.029	-10000	0	-10000	0	0
TRADD	0.01	0	-10000	0	-10000	0	0
CRADD	0.008	0.028	-10000	0	-0.52	1	1
MAPK3	0.006	0.028	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.006	0.028	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.01	0.031	-10000	0	-10000	0	0
FADD	0.027	0.047	-10000	0	-10000	0	0
KSR1	-0.009	0.032	0.14	4	-10000	0	4
MAPK8	0	0.031	-10000	0	-0.19	1	1
PRKRA	-0.009	0.032	-10000	0	-10000	0	0
PDGFA	-0.002	0.076	-10000	0	-0.5	8	8
TRAF2	0.01	0	-10000	0	-10000	0	0
IGF1	0.002	0.061	-10000	0	-0.51	5	5
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.017	0.034	0.14	4	-10000	0	4
CTSD	0.01	0	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.01	0.033	-10000	0	-10000	0	0
PRKCD	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.007	0.039	-10000	0	-0.5	2	2
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.009	0.059	-10000	0	-0.36	9	9
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.01	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.021	0.05	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.014	0.063	-10000	0	-0.3	17	17
mol:Sphingosine-1-phosphate	0.009	0.059	-10000	0	-0.36	9	9
MAP2K1	0.003	0.029	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
CYCS	-0.004	0.023	-10000	0	-10000	0	0
TNFRSF1A	0.01	0	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0	0	-10000	0	-10000	0	0
EIF2AK2	-0.003	0.03	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.014	0.063	-10000	0	-0.3	17	17
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.028	0.03	-10000	0	-10000	0	0
MAP2K2	0.003	0.029	-10000	0	-10000	0	0
SMPD3	0.014	0.047	-10000	0	-0.29	1	1
TNF	-0.015	0.11	-10000	0	-0.5	17	17
PKC zeta/PAR4	-0.002	0.027	-10000	0	-0.36	2	2
mol:PHOSPHOCHOLINE	0.023	0.069	0.16	65	-10000	0	65
NF kappa B1/RelA/I kappa B alpha	-0.001	0.018	-10000	0	-10000	0	0
AIFM1	-0.004	0.023	-10000	0	-10000	0	0
BCL2	0.007	0.04	-10000	0	-0.52	2	2

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.01	0	-10000	0	-10000	0	0
NFATC1	0.036	0.041	-10000	0	-0.41	1	1
NFATC2	0.013	0.044	-10000	0	-0.22	4	4
NFATC3	0.013	0.03	-10000	0	-0.37	2	2
YWHAE	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.008	0.091	-10000	0	-0.44	7	7
Exportin 1/Ran/NUP214	-0.002	0.023	-10000	0	-0.31	2	2
mol:DAG	-0.001	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.028	0.075	-10000	0	-0.4	9	9
BCL2/BAX	-0.002	0.028	-10000	0	-0.37	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.002	0.004	-10000	0	-10000	0	0
CaM/Ca2+	-0.002	0.004	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
MAPK14	0.008	0.004	-10000	0	-10000	0	0
BAD	0.01	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.008	0.085	-10000	0	-0.42	7	7
Calcineurin A alpha-beta B1/BCL2	0.007	0.04	-10000	0	-0.52	2	2
FKBP8	0.008	0.027	-10000	0	-0.5	1	1
activation-induced cell death of T cells	0.007	0.084	0.41	7	-10000	0	7
KPNB1	0.01	0	-10000	0	-10000	0	0
KPNA2	0.002	0.063	-10000	0	-0.52	5	5
XPO1	0.009	0.001	-10000	0	-10000	0	0
SFN	-0.002	0.079	-10000	0	-0.52	8	8
MAP3K8	0.005	0.039	-10000	0	-0.51	2	2
NFAT4/CK1 alpha	-0.001	0.015	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.053	0.1	-10000	0	-0.39	4	4
CABIN1	-0.008	0.091	-10000	0	-0.45	7	7
CALM1	0.008	0.004	-10000	0	-10000	0	0
RAN	0.006	0.04	-10000	0	-0.52	2	2
MAP3K1	0.01	0	-10000	0	-10000	0	0
CAMK4	0.004	0.055	-10000	0	-0.51	4	4
mol:Ca2+	-0.003	0.007	-10000	0	-10000	0	0
MAPK3	0.01	0	-10000	0	-10000	0	0
YWHAH	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.002	0.027	-10000	0	-0.36	2	2
YWHAB	0.01	0	-10000	0	-10000	0	0
MAPK8	0.008	0.004	-10000	0	-10000	0	0
MAPK9	0.01	0	-10000	0	-10000	0	0
YWHAG	0.01	0	-10000	0	-10000	0	0
FKBP1A	0.01	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.005	0.036	-10000	0	-0.36	2	2
PRKCH	0.01	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.002	0.004	-10000	0	-10000	0	0
CASP3	0.008	0.004	-10000	0	-10000	0	0
PIM1	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	0	0.015	0.21	1	-10000	0	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.025	0.021	-10000	0	-10000	0	0
PRKCB	0.001	0.066	-10000	0	-0.5	6	6
PRKCE	0.005	0.047	-10000	0	-0.5	3	3
JNK2/NFAT4	0.016	0.027	-10000	0	-0.33	2	2
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0.01	0	-10000	0	-10000	0	0
NUP214	0.009	0.001	-10000	0	-10000	0	0
PRKCZ	0.005	0.039	-10000	0	-0.51	2	2
PRKCA	0.007	0.039	-10000	0	-0.5	2	2
PRKCG	-0.026	0.13	-10000	0	-0.52	22	22
PRKCQ	-0.06	0.18	-10000	0	-0.5	48	48
FKBP38/BCL2	-0.003	0.034	-10000	0	-0.37	3	3
EP300	0.008	0.005	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.01	0	-10000	0	-10000	0	0
NFATc/JNK1	0.034	0.042	-10000	0	-0.38	1	1
CaM/Ca2+/FKBP38	-0.001	0.017	-10000	0	-0.31	1	1
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.012	0.009	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.003	0.032	-10000	0	-0.3	4	4
NFATc/ERK1	0.04	0.039	-10000	0	-0.38	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.028	0.074	-10000	0	-0.4	9	9
NR4A1	-0.057	0.22	-10000	0	-0.48	73	73
GSK3B	0.008	0.004	-10000	0	-10000	0	0
positive T cell selection	0.013	0.03	-10000	0	-0.36	2	2
NFAT1/CK1 alpha	-0.011	0.025	-10000	0	-0.26	1	1
RCH1/ KPNB1	-0.005	0.044	-10000	0	-0.37	5	5
YWHAQ	0.01	0	-10000	0	-10000	0	0
PRKACA	0.008	0.004	-10000	0	-10000	0	0
AKAP5	0.007	0.039	-10000	0	-0.5	2	2
MEF2D	0.008	0.005	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.01	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.034	0.042	-10000	0	-0.38	1	1
CREBBP	0.008	0.005	-10000	0	-10000	0	0
BCL2	0.007	0.04	-10000	0	-0.52	2	2

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.014	0.061	-9999	-0.29	16	16
Ran/GTP/Exportin 1/HDAC1	-0.001	0.017	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.013	0.057	-9999	-0.28	16	16
SUMO1	0.01	0	-9999	-10000	0	0
ZFPM1	0.008	0.028	-9999	-0.52	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
FKBP3	0.008	0.028	-9999	-0.52	1	1
Histones	-0.006	0.027	-9999	-10000	0	0
YY1/LSF	0.024	0	-9999	-10000	0	0
SMG5	0.01	0	-9999	-10000	0	0
RAN	0.007	0.04	-9999	-0.52	2	2
I kappa B alpha/HDAC3	-0.011	0.049	-9999	-10000	0	0
I kappa B alpha/HDAC1	-0.008	0.033	-9999	-10000	0	0
SAP18	0.01	0	-9999	-10000	0	0
RELA	0.019	0.052	-9999	-0.22	16	16
HDAC1/Smad7	-0.001	0.016	-9999	-0.29	1	1
RANGAP1	0.01	0	-9999	-10000	0	0
HDAC3/TR2	-0.008	0.033	-9999	-10000	0	0
NuRD/MBD3 Complex	0.037	0.014	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.021	0.048	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.037	0.15	-9999	-0.5	32	32
GATA1	-0.044	0.16	-9999	-0.5	36	36
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.024	0.063	-9999	-0.28	1	1
RBBP7	0.01	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.01	0	-9999	-10000	0	0
MAX	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.01	0	-9999	-10000	0	0
NFKBIA	0.013	0.044	-9999	-10000	0	0
KAT2B	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.035	0	-9999	-10000	0	0
SIN3 complex	0	0	-9999	-10000	0	0
SMURF1	0.01	0	-9999	-10000	0	0
CHD3	0.01	0	-9999	-10000	0	0
SAP30	0.01	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.01	0	-9999	-10000	0	0
YY1/HDAC3	-0.006	0.029	-9999	-10000	0	0
YY1/HDAC2	0.024	0	-9999	-10000	0	0
YY1/HDAC1	0.024	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.038	0	-9999	-10000	0	0
PPARG	-0.052	0.12	-9999	-0.31	58	58
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-9999	-10000	0	0
TNFRSF1A	0.01	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.008	0.033	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.001	0.016	-9999	-0.29	1	1
CREBBP	0.01	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.039	0.015	-9999	-10000	0	0
HDAC1	0.01	0	-9999	-10000	0	0
HDAC3	0.013	0.044	-9999	-10000	0	0
HDAC2	0.01	0	-9999	-10000	0	0
YY1	0.024	0	-9999	-10000	0	0
HDAC8	0.01	0	-9999	-10000	0	0
SMAD7	0.008	0.027	-9999	-0.5	1	1
NCOR2	0.01	0	-9999	-10000	0	0
MXD1	0.01	0	-9999	-10000	0	0
STAT3	0.02	0	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0	0	-9999	-10000	0	0
YY1/SAP30/HDAC1	0	0	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.02	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.013	0.044	-9999	-10000	0	0
histone deacetylation	0.038	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.007	0.029	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GATAD2B	0.01	0	-9999	-10000	0	0
GATAD2A	0.01	0	-9999	-10000	0	0
GATA2/HDAC3	-0.031	0.085	-9999	-0.43	4	4
GATA1/HDAC1	-0.036	0.11	-9999	-0.36	36	36
GATA1/HDAC3	-0.034	0.086	-9999	-0.43	2	2
CHD4	0.01	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.017	0.076	-9999	-0.36	17	17
SIN3/HDAC complex/Mad/Max	0.038	0	-9999	-10000	0	0
NuRD Complex	0.043	0.015	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.006	0.027	-9999	-10000	0	0
SIN3B	0.01	0	-9999	-10000	0	0
MTA2	0.01	0	-9999	-10000	0	0
SIN3A	0.01	0	-9999	-10000	0	0
XPO1	0.01	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
HDAC complex	0	0	-9999	-10000	0	0
GATA1/Fog1	-0.037	0.11	-9999	-0.36	36	36
FKBP25/HDAC1/HDAC2	-0.001	0.016	-9999	-0.31	1	1
TNF	-0.015	0.11	-9999	-0.5	17	17
negative regulation of cell growth	0.038	0	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.038	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	-0.001	0.017	-9999	-0.23	2	2
NF kappa B/RelA/I kappa B alpha	-0.014	0.061	-9999	-0.29	16	16
SIN3/HDAC complex/NCoR1	0.036	0	-9999	-10000	0	0
TFCP2	0.01	0	-9999	-10000	0	0
NR2C1	0.01	0	-9999	-10000	0	0
MBD3	0.007	0.039	-9999	-0.5	2	2
MBD2	0.01	0	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.047	0.039	-10000	0	-0.44	1	1
UGCG	-0.001	0.007	-10000	0	-10000	0	0
AKT1/mTOR/p70S6K/Hsp90/TERT	0.042	0.057	-10000	0	-0.31	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.022	0.013	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.006	0.037	-10000	0	-0.31	4	4
FRAP1	0.063	0.058	-10000	0	-0.36	4	4
FOXO3	0.064	0.055	-10000	0	-0.36	3	3
AKT1	0.061	0.058	-10000	0	-0.38	3	3
GAB2	0.005	0.054	-10000	0	-0.5	4	4
SMPD1	-0.001	0.007	-10000	0	-10000	0	0
SGMS1	-0.001	0.007	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.002	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
cell proliferation	0.039	0.031	-10000	0	-10000	0	0
EIF3A	0.01	0	-10000	0	-10000	0	0
PI3K	0.019	0.003	-10000	0	-10000	0	0
RPS6KB1	0.022	0.02	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.001	-10000	0	-10000	0	0
natural killer cell activation	0.001	0.001	-10000	0	-0.011	2	2
JAK3	0.012	0.001	-10000	0	-10000	0	0
PIK3R1	0.012	0.001	-10000	0	-10000	0	0
JAK1	0.012	0.001	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
MYC	0.06	0.086	-10000	0	-0.92	2	2
MYB	0.019	0.092	-10000	0	-1.1	2	2
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.053	0.053	-10000	0	-0.38	2	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.031	0.018	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.053	0.052	-10000	0	-0.37	2	2
Rac1/GDP	0.023	0.003	-10000	0	-10000	0	0
T cell proliferation	0.056	0.055	-10000	0	-0.37	2	2
SHC1	0.01	0.001	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.006	-10000	0	-0.049	4	4
PRKCZ	0.056	0.056	-10000	0	-0.38	2	2
NF kappa B1 p50/RelA	-0.004	0.036	-10000	0	-0.33	1	1
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.043	0.042	-10000	0	-0.43	2	2
HSP90AA1	0.01	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
IL2RA	-0.035	0.15	-10000	0	-0.52	30	30
IL2RB	0.009	0.039	-10000	0	-0.5	2	2
TERT	-0.13	0.23	-10000	0	-0.52	93	93
E2F1	0.02	0.038	-10000	0	-0.42	2	2
SOS1	0.01	0.001	-10000	0	-10000	0	0
RPS6	0.01	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.003	0.023	4	-10000	0	4
PTPN11	0.011	0.001	-10000	0	-10000	0	0
IL2RG	0.007	0.055	-10000	0	-0.5	4	4
actin cytoskeleton organization	0.056	0.055	-10000	0	-0.37	2	2
GRB2	0.01	0.001	-10000	0	-10000	0	0
IL2	0.008	0.005	-10000	0	-10000	0	0
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
Rac1/GTP	0.028	0.004	-10000	0	-10000	0	0
LCK	0.009	0.039	-10000	0	-0.51	2	2
BCL2	0.064	0.055	-10000	0	-0.42	1	1

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.023	0.019	-10000	0	-0.23	2	2
epithelial cell differentiation	-0.001	0.018	-10000	0	-0.24	2	2
CYFIP2	0.002	0.061	-10000	0	-0.5	5	5
ENAH	0.049	0.03	-10000	0	-0.29	1	1
EGFR	-0.005	0.087	-10000	0	-0.52	10	10
EPHA2	0.002	0.061	-10000	0	-0.5	5	5
MYO6	0.029	0.019	-10000	0	-10000	0	0
CTNNB1	0.01	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.004	0.035	-10000	0	-0.29	5	5
AQP5	-0.1	0.17	-10000	0	-0.42	79	79
CTNND1	0.01	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.029	0.019	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.12	0.13	-10000	0	-0.47	1	1
EGF	-0.091	0.21	-10000	0	-0.52	67	67
NCKAP1	0.01	0	-10000	0	-10000	0	0
AQP3	-0.022	0.096	-10000	0	-0.44	17	17
cortical microtubule organization	-0.001	0.018	-10000	0	-0.24	2	2
GO:0000145	0.028	0.018	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.001	0.018	-10000	0	-0.24	2	2
MLLT4	0.01	0	-10000	0	-10000	0	0
ARF6/GDP	-0.004	0.031	-10000	0	-0.4	1	1
ARF6	0.01	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.004	0.034	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.038	0.02	-10000	0	-10000	0	0
PVRL2	0.01	0	-10000	0	-10000	0	0
ZYX	0.029	0.019	-10000	0	-10000	0	0
ARF6/GTP	-0.004	0.03	-10000	0	-10000	0	0
CDH1	0.007	0.039	-10000	0	-0.5	2	2
EGFR/EGFR/EGF/EGF	-0.051	0.098	-10000	0	-0.47	2	2
RhoA/GDP	-0.001	0.017	-10000	0	-10000	0	0
actin cytoskeleton organization	0.034	0.019	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.008	0.027	-10000	0	-0.5	1	1
GIT1	0.01	0	-10000	0	-10000	0	0
IGF1R	0.008	0.027	-10000	0	-0.5	1	1
IGF1	0.002	0.061	-10000	0	-0.51	5	5
DIAPH1	-0.008	0.064	-10000	0	-0.55	5	5
Wnt receptor signaling pathway	0.001	0.018	0.24	2	-10000	0	2
RHOA	0.01	0	-10000	0	-10000	0	0
RhoA/GTP	-0.004	0.031	-10000	0	-0.4	1	1
CTNNA1	0.01	0	-10000	0	-10000	0	0
VCL	0.034	0.019	-10000	0	-10000	0	0
EFNA1	0.008	0.027	-10000	0	-0.5	1	1
LPP	0.034	0.023	-10000	0	-10000	0	0
Ephrin A1/EPHA2	-0.005	0.037	-10000	0	-0.46	1	1
SEC6/SEC8	-0.001	0.014	-10000	0	-10000	0	0
MGAT3	-0.12	0.13	-10000	0	-0.48	1	1
HGF/MET	-0.027	0.081	-10000	0	-0.46	4	4
HGF	-0.017	0.11	-10000	0	-0.51	18	18
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.023	0.019	-10000	0	-0.23	2	2
actin cable formation	0.061	0.029	-10000	0	-10000	0	0
KIAA1543	0.033	0.032	-10000	0	-0.45	1	1
KIFC3	0.028	0.024	-10000	0	-10000	0	0
NCK1	0.01	0	-10000	0	-10000	0	0
EXOC3	0.01	0	-10000	0	-10000	0	0
ACTN1	0.029	0.019	-10000	0	-10000	0	0
NCK1/GIT1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.001	0.018	-10000	0	-0.24	2	2
EXOC4	0.01	0	-10000	0	-10000	0	0
STX4	0.029	0.019	-10000	0	-10000	0	0
PIP5K1C	0.029	0.019	-10000	0	-10000	0	0
LIMA1	0.01	0	-10000	0	-10000	0	0
ABI1	0.01	0	-10000	0	-10000	0	0
ROCK1	-0.004	0.027	-10000	0	-0.35	1	1
adherens junction assembly	0.044	0.045	-10000	0	-0.53	2	2
IGF-1R heterotetramer/IGF1	-0.005	0.032	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-10000	0	-10000	0	0
MET	-0.024	0.13	-10000	0	-0.51	23	23
PLEKHA7	0.029	0.019	-10000	0	-10000	0	0
mol:GTP	-0.004	0.033	-10000	0	-10000	0	0
establishment of epithelial cell apical/basal polarity	0.049	0.017	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	0.023	0.019	-10000	0	-0.23	2	2
regulation of cell-cell adhesion	0.034	0.019	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.023	0.019	-10000	0	-0.23	2	2

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.003	0.023	-9999	-10000	0	0
DAPP1	-0.001	0.11	-9999	-0.49	11	11
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.002	0.16	-9999	-0.61	16	16
mol:DAG	0.024	0.07	-9999	-0.25	13	13
HRAS	0.01	0.001	-9999	-10000	0	0
RAP1A	0.01	0.001	-9999	-10000	0	0
ARF5/GDP	0.021	0.073	-9999	-0.46	6	6
PLCG2	0.005	0.047	-9999	-0.5	3	3
PLCG1	0.01	0	-9999	-10000	0	0
ARF5	0.01	0	-9999	-10000	0	0
mol:GTP	-0.002	0.019	-9999	-10000	0	0
ARF1/GTP	-0.002	0.02	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
YES1	0.01	0	-9999	-10000	0	0
RAP1A/GTP	-0.002	0.018	-9999	-10000	0	0
ADAP1	-0.002	0.027	-9999	-0.43	1	1
ARAP3	-0.002	0.019	-9999	-10000	0	0
INPPL1	0.01	0	-9999	-10000	0	0
PREX1	0.001	0.066	-9999	-0.5	6	6
ARHGEF6	-0.005	0.085	-9999	-0.5	10	10
ARHGEF7	0.01	0	-9999	-10000	0	0
ARF1	0.01	0	-9999	-10000	0	0
NRAS	0.01	0.001	-9999	-10000	0	0
FYN	0.01	0	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
FGR	-0.037	0.15	-9999	-0.5	32	32
mol:Ca2+	0.021	0.038	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.001	0.066	-9999	-0.5	6	6
ZAP70	0.001	0.066	-9999	-0.5	6	6
mol:IP3	0.025	0.051	-9999	-0.21	5	5
LYN	0.01	0	-9999	-10000	0	0
ARF1/GDP	0.021	0.073	-9999	-0.46	6	6
RhoA/GDP	-0.006	0.037	-9999	-0.37	2	2
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
BLNK	0.008	0.027	-9999	-0.5	1	1
actin cytoskeleton reorganization	0.039	0.066	-9999	-0.47	4	4
SRC	0.01	0	-9999	-10000	0	0
PLEKHA2	0.021	0.029	-9999	-0.29	3	3
RAC1	0.01	0	-9999	-10000	0	0
PTEN	0	0.003	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
ARF6/GTP	-0.002	0.017	-9999	-10000	0	0
RhoA/GTP	-0.002	0.017	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	0	0.12	-9999	-0.5	12	12
BLK	-0.054	0.17	-9999	-0.52	42	42
PDPK1	0.01	0	-9999	-10000	0	0
CYTH1	-0.002	0.017	-9999	-10000	0	0
HCK	-0.011	0.1	-9999	-0.5	14	14
CYTH3	-0.003	0.024	-9999	-10000	0	0
CYTH2	-0.002	0.017	-9999	-10000	0	0
KRAS	0.01	0.001	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.002	0.031	-9999	-0.57	1	1
SGK1	-0.002	0.034	-9999	-0.63	1	1
INPP5D	0.007	0.039	-9999	-0.5	2	2
mol:GDP	0.016	0.077	-9999	-0.49	6	6
SOS1	0.01	0	-9999	-10000	0	0
SYK	0.005	0.047	-9999	-0.5	3	3
ARF6/GDP	-0.006	0.037	-9999	-0.37	2	2
mol:PI-3-4-5-P3	-0.002	0.019	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.002	0.019	-9999	-10000	0	0
VAV1	0.002	0.061	-9999	-0.5	5	5
mol:PI-3-4-P2	0.016	0.028	-9999	-0.36	2	2
RAS family/GTP/PI3K Class I	-0.002	0.019	-9999	-10000	0	0
PLEKHA1	0.022	0.024	-9999	-0.29	2	2
Rac1/GDP	0.021	0.073	-9999	-0.46	6	6
LAT	0.008	0.028	-9999	-0.52	1	1
Rac1/GTP	0.013	0.11	-9999	-0.5	12	12
ITK	-0.007	0.039	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.024	0.094	-9999	-0.36	13	13
LCK	0.007	0.039	-9999	-0.51	2	2
BTK	-0.015	0.061	-9999	-0.43	2	2

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.004	0.055	-10000	0	-0.51	4	4
positive regulation of NF-kappaB transcription factor activity	-0.006	0.046	-10000	0	-0.36	6	6
MAP2K4	0.035	0.025	-10000	0	-10000	0	0
IKBKB	0.01	0	-10000	0	-10000	0	0
TNFRSF10B	0.01	0	-10000	0	-10000	0	0
TNFRSF10A	0.008	0.027	-10000	0	-0.5	1	1
SMPD1	-0.002	0.019	-10000	0	-0.19	3	3
IKBKG	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.007	0.039	-10000	0	-0.5	2	2
TRAIL/TRAILR2	-0.004	0.038	-10000	0	-0.36	4	4
TRAIL/TRAILR3	-0.01	0.064	-10000	0	-0.39	9	9
TRAIL/TRAILR1	-0.005	0.042	-10000	0	-0.36	5	5
TRAIL/TRAILR4	-0.006	0.046	-10000	0	-0.36	6	6
TRAIL/TRAILR1/DAP3/GTP	-0.004	0.032	-10000	0	-0.27	5	5
IKK complex	-0.001	0.012	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0	-10000	0	-10000	0	0
MAPK3	0.014	0.04	-10000	0	-0.36	4	4
MAP3K1	-0.003	0.022	-10000	0	-10000	0	0
TRAILR4 (trimer)	0.007	0.038	-10000	0	-0.5	2	2
TRADD	0.01	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.008	0.027	-10000	0	-0.5	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.026	0.028	-10000	0	-10000	0	0
CFLAR	0.01	0	-10000	0	-10000	0	0
MAPK1	0.014	0.04	-10000	0	-0.36	4	4
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.003	0.028	-10000	0	-10000	0	0
mol:ceramide	-0.002	0.019	-10000	0	-0.19	3	3
FADD	0.01	0	-10000	0	-10000	0	0
MAPK8	0.04	0.024	-10000	0	-10000	0	0
TRAF2	0.01	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.001	0.066	-10000	0	-0.5	6	6
CHUK	0.01	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.004	0.035	-10000	0	-0.3	5	5
DAP3	0.01	0	-10000	0	-10000	0	0
CASP10	-0.003	0.036	0.24	1	-0.29	4	5
JNK cascade	-0.006	0.046	-10000	0	-0.36	6	6
TRAIL (trimer)	0.004	0.055	-10000	0	-0.51	4	4
TNFRSF10C	0.001	0.066	-10000	0	-0.5	6	6
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.003	0.029	-10000	0	-0.25	5	5
TRAIL/TRAILR2/FADD	-0.003	0.032	-10000	0	-0.3	4	4
cell death	-0.002	0.019	-10000	0	-0.19	3	3
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.027	0.024	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.01	0	-10000	0	-10000	0	0
CASP8	0.001	0.011	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.003	0.026	-10000	0	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.005	0.047	-10000	0	-0.5	3	3
HRAS	0.01	0	-10000	0	-10000	0	0
EGFR	-0.005	0.087	-10000	0	-0.52	10	10
AKT	0.029	0.036	-10000	0	-0.34	3	3
FOXO3	0.01	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
FOXO1	0.01	0	-10000	0	-10000	0	0
AKT3	0.005	0.047	-10000	0	-0.5	3	3
FOXO4	0.01	0	-10000	0	-10000	0	0
MET	-0.024	0.13	-10000	0	-0.51	23	23
PIK3CA	0.01	0	-10000	0	-10000	0	0
PIK3CB	0.01	0	-10000	0	-10000	0	0
NRAS	0.01	0	-10000	0	-10000	0	0
PIK3CG	-0.002	0.076	-10000	0	-0.5	8	8
PIK3R3	0.008	0.027	-10000	0	-0.5	1	1
PIK3R2	0.01	0	-10000	0	-10000	0	0
NF1	0.01	0	-10000	0	-10000	0	0
RAS	0.009	0.043	-10000	0	-0.26	3	3
ERBB2	0.007	0.04	-10000	0	-0.52	2	2
proliferation/survival/translation	-0.021	0.029	0.2	3	-10000	0	3
PI3K	0.016	0.046	-10000	0	-0.24	4	4
PIK3R1	0.01	0	-10000	0	-10000	0	0
KRAS	0.01	0	-10000	0	-10000	0	0
FOXO	0.037	0.013	-10000	0	-10000	0	0
AKT2	0.01	0	-10000	0	-10000	0	0
PTEN	0.01	0	-10000	0	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.031	0.034	-9999	-0.42	2	2
KLHL20	-0.013	0.034	-9999	-0.25	1	1
CYFIP2	0.002	0.061	-9999	-0.5	5	5
Rac1/GDP	0.05	0.024	-9999	-10000	0	0
ENAH	0.031	0.034	-9999	-0.42	2	2
AP1M1	0.01	0	-9999	-10000	0	0
RAP1B	0.01	0	-9999	-10000	0	0
RAP1A	0.01	0	-9999	-10000	0	0
CTNNB1	0.01	0	-9999	-10000	0	0
CDC42/GTP	-0.001	0.012	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.01	0.024	-9999	-0.16	1	1
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.002	0.024	-9999	-0.26	3	3
RAPGEF1	0.041	0.03	-9999	-0.35	2	2
CTNND1	0.01	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.002	0.033	-9999	-0.43	2	2
CRK	0.036	0.032	-9999	-0.39	2	2
E-cadherin/gamma catenin/alpha catenin	-0.003	0.027	-9999	-0.3	3	3
alphaE/beta7 Integrin	-0.001	0.019	-9999	-0.36	1	1
IQGAP1	0.01	0	-9999	-10000	0	0
NCKAP1	0.01	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	0.031	0.034	-9999	-0.42	2	2
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.009	-9999	-10000	0	0
MLLT4	0.01	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.039	0.1	-9999	-0.29	47	47
PI3K	-0.001	0.011	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.003	0.033	-9999	-0.36	3	3
TIAM1	0.001	0.066	-9999	-0.5	6	6
E-cadherin(dimer)/Ca2+	-0.001	0.018	-9999	-0.24	2	2
AKT1	0	0.007	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
CDH1	0.007	0.039	-9999	-0.5	2	2
RhoA/GDP	0.05	0.024	-9999	-10000	0	0
actin cytoskeleton organization	-0.01	0.026	-9999	-0.18	1	1
CDC42/GDP	0.05	0.024	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.018	0.021	-9999	-0.23	2	2
ITGB7	0.008	0.027	-9999	-0.5	1	1
RAC1	0.01	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.001	0.02	-9999	-0.26	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.001	0.019	-9999	-0.25	2	2
mol:GDP	0.049	0.027	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.008	0.028	-9999	-0.52	1	1
p120 catenin/RhoA/GDP	-0.001	0.018	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0
CTNNA1	0.01	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.018	0.032	-9999	-0.2	3	3
NME1	-0.055	0.17	-9999	-0.52	43	43
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.031	0.034	-9999	-0.42	2	2
regulation of cell-cell adhesion	-0.001	0.011	-9999	-10000	0	0
WASF2	-0.005	0.012	-9999	-10000	0	0
Rap1/GTP	-0.001	0.014	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.003	0.026	-9999	-10000	0	0
CCND1	0.02	0.039	-9999	-0.25	3	3
VAV2	0.038	0.048	-9999	-0.47	3	3
RAP1/GDP	-0.001	0.016	-9999	-10000	0	0
adherens junction assembly	0.031	0.033	-9999	-0.4	2	2
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.01	0	-9999	-10000	0	0
PIP5K1C	0.01	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.003	0.024	-9999	-10000	0	0
E-cadherin/beta catenin	-0.002	0.026	-9999	-0.34	2	2
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.031	0.034	-9999	-0.42	2	2
PIK3CA	0.01	0	-9999	-10000	0	0
Rac1/GTP	-0.021	0.054	-9999	-0.42	1	1
E-cadherin/beta catenin/alpha catenin	-0.002	0.022	-9999	-0.29	2	2
ITGAE	0.01	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.003	0.033	-9999	-0.44	2	2

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.008	0.027	-9999	-0.5	1	1
mol:S1P	0.001	0.003	-9999	-10000	0	0
S1P1/S1P/Gi	0.004	0.078	-9999	-0.24	30	30
GNAO1	0.007	0.049	-9999	-0.52	3	3
S1P/S1P3/G12/G13	-0.001	0.015	-9999	-0.28	1	1
AKT1	-0.008	0.039	-9999	-0.62	1	1
AKT3	0.021	0.11	-9999	-1.1	3	3
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.008	0.027	-9999	-0.5	1	1
GNAI2	0.011	0.002	-9999	-10000	0	0
GNAI3	0.011	0.002	-9999	-10000	0	0
GNAI1	0.008	0.039	-9999	-0.5	2	2
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.009	0.028	-9999	-0.52	1	1
S1PR2	0.01	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.013	0.074	-9999	-0.48	2	2
MAPK3	0.019	0.07	-9999	-0.45	2	2
MAPK1	0.019	0.07	-9999	-0.45	2	2
JAK2	0.022	0.07	-9999	-0.45	2	2
CXCR4	0.019	0.07	-9999	-0.45	2	2
FLT1	0.012	0.003	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.019	0.07	-9999	-0.45	2	2
S1P/S1P3/Gi	0.013	0.074	-9999	-0.48	2	2
RAC1	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.017	0.056	-9999	-0.43	2	2
VEGFA	0.012	0.003	-9999	-10000	0	0
S1P/S1P2/Gi	0.011	0.07	-9999	-0.42	2	2
VEGFR1 homodimer/VEGFA homodimer	0.021	0.006	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.015	0.057	-9999	-0.26	13	13
GNAQ	0.008	0.027	-9999	-0.5	1	1
GNAZ	-0.03	0.14	-9999	-0.5	28	28
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.008	0.093	-9999	-0.5	12	12
GNA15	0.01	0	-9999	-10000	0	0
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
GNA11	0.008	0.027	-9999	-0.5	1	1
Rac1/GTP	-0.017	0.056	-9999	-0.43	2	2

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.066	0.015	-9999	-10000	0	0
ERC1	0.01	0	-9999	-10000	0	0
RIP2/NOD2	-0.001	0.019	-9999	-0.36	1	1
NFKBIA	0.037	0	-9999	-10000	0	0
BIRC2	0.01	0	-9999	-10000	0	0
IKBKB	0.01	0	-9999	-10000	0	0
RIPK2	0.01	0	-9999	-10000	0	0
IKBKG	-0.001	0.01	-9999	-10000	0	0
IKK complex/A20	-0.01	0.042	-9999	-10000	0	0
NEMO/A20/RIP2	0.01	0	-9999	-10000	0	0
XPO1	0.01	0	-9999	-10000	0	0
NEMO/ATM	0.04	0.011	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.007	0.04	-9999	-0.52	2	2
Exportin 1/RanGTP	-0.002	0.024	-9999	-0.32	2	2
IKK complex/ELKS	0	0.008	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	0.008	0.027	-9999	-0.5	1	1
NFKB1	0.012	0	-9999	-10000	0	0
RELA	0.012	0	-9999	-10000	0	0
MALT1	0.01	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.01	0	-9999	-10000	0	0
TNF/TNFR1A	-0.017	0.076	-9999	-0.36	17	17
TRAF6	0.01	0	-9999	-10000	0	0
PRKCA	0.007	0.039	-9999	-0.5	2	2
CHUK	0.01	0	-9999	-10000	0	0
UBE2D3	0.01	0	-9999	-10000	0	0
TNF	-0.015	0.11	-9999	-0.5	17	17
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.01	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.037	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.012	0	-9999	-10000	0	0
TNFRSF1A	0.01	0	-9999	-10000	0	0
IKK complex	0	0.008	-9999	-10000	0	0
CYLD	0.01	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.001	0.016	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.01	0	-9999	-10000	0	0
ITGB7	0.008	0.027	-9999	-0.5	1	1
ITGA4	0.007	0.039	-9999	-0.5	2	2
alpha4/beta7 Integrin	-0.003	0.033	-9999	-0.36	3	3
alpha4/beta1 Integrin	-0.002	0.027	-9999	-0.36	2	2

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.01	0	-9999	-10000	0	0
Caspase 8 (4 units)	-0.005	0.032	-9999	-0.28	2	2
NEF	0.002	0.02	-9999	-10000	0	0
NFKBIA	0.011	0.013	-9999	-10000	0	0
BIRC3	0.027	0.067	-9999	-0.48	6	6
CYCS	0.037	0.042	-9999	-0.29	1	1
RIPK1	0.01	0	-9999	-10000	0	0
CD247	0.005	0.062	-9999	-0.54	4	4
MAP2K7	0.036	0.036	-9999	-0.26	1	1
protein ubiquitination	0.049	0.036	-9999	-10000	0	0
CRADD	0.008	0.028	-9999	-0.52	1	1
DAXX	0.01	0	-9999	-10000	0	0
FAS	0.005	0.047	-9999	-0.5	3	3
BID	0.032	0.043	-9999	-0.3	2	2
NF-kappa-B/RelA/I kappa B alpha	-0.004	0.031	-9999	-10000	0	0
TRADD	0.01	0	-9999	-10000	0	0
MAP3K5	0.01	0	-9999	-10000	0	0
CFLAR	0.01	0	-9999	-10000	0	0
FADD	0.01	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.004	0.032	-9999	-10000	0	0
MAPK8	0.041	0.034	-9999	-10000	0	0
APAF1	0.01	0	-9999	-10000	0	0
TRAF1	0.01	0	-9999	-10000	0	0
TRAF2	0.01	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.026	0.045	-9999	-0.28	7	7
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.041	0.043	-9999	-10000	0	0
CHUK	0.05	0.038	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.002	0.022	-9999	-10000	0	0
TCRz/NEF	-0.008	0.056	-9999	-0.36	8	8
TNF	-0.015	0.11	-9999	-0.5	17	17
FASLG	0.011	0.084	-9999	-0.51	8	8
NFKB1	0.011	0.013	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.014	0.063	-9999	-0.3	17	17
CASP6	-0.003	0.023	-9999	-10000	0	0
CASP7	0.061	0.06	-9999	-0.53	2	2
RELA	0.011	0.013	-9999	-10000	0	0
CASP2	0.01	0	-9999	-10000	0	0
CASP3	0.061	0.06	-9999	-0.53	2	2
TNFRSF1A	0.01	0	-9999	-10000	0	0
TNFR1A/BAG4	0	0	-9999	-10000	0	0
CASP8	0.01	0	-9999	-10000	0	0
CASP9	0.01	0	-9999	-10000	0	0
MAP3K14	0.046	0.041	-9999	-10000	0	0
APAF-1/Caspase 9	-0.008	0.045	-9999	-0.48	1	1
BCL2	0.044	0.04	-9999	-0.37	1	1

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.01	0	-10000	0	-10000	0	0
PTK2	0.01	0	-10000	0	-10000	0	0
CRKL	0.017	0.039	-10000	0	-0.28	5	5
GRB2/SOS1/SHC	0	0	-10000	0	-10000	0	0
HRAS	0.01	0	-10000	0	-10000	0	0
IRS1/Crk	0.016	0.039	-10000	0	-0.28	5	5
IGF-1R heterotetramer/IGF1/PTP1B	-0.005	0.037	-10000	0	-0.28	6	6
AKT1	0.033	0.034	-10000	0	-0.38	1	1
BAD	0.038	0.032	-10000	0	-0.36	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.017	0.039	-10000	0	-0.28	5	5
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.005	0.037	-10000	0	-0.46	1	1
RAF1	0.04	0.031	-10000	0	-0.34	1	1
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.004	0.034	-10000	0	-0.44	1	1
YWHAZ	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.005	0.04	-10000	0	-0.32	5	5
PIK3CA	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.033	0.034	-10000	0	-0.38	1	1
GNB2L1	0.01	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.035	0.028	-10000	0	-0.3	1	1
PXN	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.004	0.03	-10000	0	-0.39	1	1
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.004	0.028	-10000	0	-0.26	1	1
IGF-1R heterotetramer	0.008	0.029	-10000	0	-0.51	1	1
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.005	0.037	-10000	0	-0.29	5	5
Crk/p130 Cas/Paxillin	-0.005	0.034	-10000	0	-0.42	1	1
IGF1R	0.008	0.029	-10000	0	-0.51	1	1
IGF1	0.002	0.063	-10000	0	-0.52	5	5
IRS2/Crk	0.021	0.04	-10000	0	-0.44	1	1
PI3K	-0.004	0.034	-10000	0	-0.44	1	1
apoptosis	-0.04	0.029	0.31	1	-10000	0	1
HRAS/GDP	0	0	-10000	0	-10000	0	0
PRKCD	0.028	0.046	-10000	0	-0.37	4	4
RAF1/14-3-3 E	0.043	0.028	-10000	0	-10000	0	0
BAD/14-3-3	0.041	0.03	-10000	0	-0.33	1	1
PRKCZ	0.031	0.039	-10000	0	-0.38	1	1
Crk/p130 Cas/Paxillin/FAK1	-0.003	0.026	-10000	0	-0.33	1	1
PTPN1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.023	0.048	-10000	0	-0.37	5	5
BCAR1	0.008	0.027	-10000	0	-0.5	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.004	0.031	-10000	0	-0.29	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.01	0	-10000	0	-10000	0	0
IRS1/NCK2	0.016	0.039	-10000	0	-0.28	5	5
GRB10	0.01	0	-10000	0	-10000	0	0
PTPN11	0.017	0.039	-10000	0	-0.46	1	1
IRS1	0.01	0.042	-10000	0	-0.3	6	6
IRS2	0.016	0.042	-10000	0	-0.28	6	6
IGF-1R heterotetramer/IGF1	-0.007	0.05	-10000	0	-0.38	6	6
GRB2	0.01	0	-10000	0	-10000	0	0
PDPK1	0.027	0.036	-10000	0	-0.41	1	1
YWHAE	0.01	0	-10000	0	-10000	0	0
PRKD1	0.018	0.07	-10000	0	-0.43	4	4
SHC1	0.01	0	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.005	0.035	-10000	0	-0.25	7	7
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.001	0.029	-10000	0	-0.38	2	2
GNB1/GNG2	-0.001	0.016	-10000	0	-0.3	1	1
GNB1	0.01	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0	-10000	0	-10000	0	0
Gs family/GTP	-0.005	0.037	-10000	0	-0.28	6	6
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.001	0.01	0.075	6	-10000	0	6
GNAL	0.001	0.067	-10000	0	-0.51	6	6
GNG2	0.008	0.027	-10000	0	-0.5	1	1
CRH	0	0.04	-10000	0	-0.52	2	2
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0	-10000	0	-10000	0	0
MAPK11	0.004	0.03	-10000	0	-0.32	3	3

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.005	0.037	-9999	-0.55	1	1
PDGFB-D/PDGFRB/SLAP	-0.008	0.058	-9999	-0.4	7	7
PDGFB-D/PDGFRB/APS/CBL	-0.002	0.022	-9999	-0.3	2	2
AKT1	0.044	0.032	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.024	0.046	-9999	-0.59	1	1
PIK3CA	0.01	0	-9999	-10000	0	0
FGR	-0.045	0.15	-9999	-0.51	32	32
mol:Ca2+	0.021	0.043	-9999	-0.63	1	1
MYC	0.03	0.079	-9999	-0.68	3	3
SHC1	0.01	0	-9999	-10000	0	0
HRAS/GDP	0.002	0.015	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	-0.009	0.066	-9999	-0.4	8	8
GRB10	0.01	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
GO:0007205	0.021	0.043	-9999	-0.65	1	1
PTEN	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
GRB7	0.002	0.062	-9999	-0.52	5	5
PDGFB-D/PDGFRB/SHP2	-0.001	0.019	-9999	-0.36	1	1
PDGFB-D/PDGFRB/GRB10	-0.001	0.019	-9999	-0.36	1	1
cell cycle arrest	-0.008	0.058	-9999	-0.4	7	7
HRAS	0.01	0	-9999	-10000	0	0
HIF1A	0.048	0.029	-9999	-10000	0	0
GAB1	0.02	0.053	-9999	-0.64	1	1
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.024	0.049	-9999	-0.57	1	1
PDGFB-D/PDGFRB	0.005	0.02	-9999	-0.31	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.001	0.019	-9999	-0.36	1	1
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.005	0.037	-9999	-0.51	1	1
positive regulation of MAPKKK cascade	-0.001	0.019	-9999	-0.36	1	1
PIK3R1	0.01	0	-9999	-10000	0	0
mol:IP3	0.021	0.044	-9999	-0.65	1	1
E5	0	0.001	-9999	-10000	0	0
CSK	0.009	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.006	0.047	-9999	-0.37	6	6
SHB	0.008	0.027	-9999	-0.5	1	1
BLK	-0.013	0.054	-9999	-0.46	4	4
PTPN2	0.01	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.001	0.019	-9999	-0.36	1	1
BCAR1	0.008	0.027	-9999	-0.5	1	1
VAV2	0.019	0.07	-9999	-0.55	2	2
CBL	0.01	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.001	0.019	-9999	-0.36	1	1
LCK	-0.001	0.033	-9999	-0.42	2	2
PDGFRB	0.009	0.028	-9999	-0.51	1	1
ACP1	0.01	0	-9999	-10000	0	0
HCK	-0.019	0.11	-9999	-0.55	14	14
ABL1	0.017	0.054	-9999	-0.61	1	1
PDGFB-D/PDGFRB/CBL	0.018	0.059	-9999	-0.73	1	1
PTPN1	0.01	0.001	-9999	-10000	0	0
SNX15	0.01	0	-9999	-10000	0	0
STAT3	0.01	0	-9999	-10000	0	0
STAT1	0.01	0	-9999	-10000	0	0
cell proliferation	0.03	0.072	-9999	-0.6	3	3
SLA	0	0.072	-9999	-0.5	7	7
actin cytoskeleton reorganization	0.007	0.026	-9999	-10000	0	0
SRC	0.001	0.02	-9999	-0.34	1	1
PI3K	-0.004	0.027	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.005	0.039	-9999	-0.3	6	6
SH2B2	0.008	0.027	-9999	-0.5	1	1
PLCgamma1/SPHK1	0.024	0.047	-9999	-0.62	1	1
LYN	0.002	0.02	-9999	-0.34	1	1
LRP1	0.004	0.054	-9999	-0.5	4	4
SOS1	0.01	0	-9999	-10000	0	0
STAT5B	0.01	0	-9999	-10000	0	0
STAT5A	0.008	0.027	-9999	-0.5	1	1
NCK1-2/p130 Cas	0.002	0.02	-9999	-10000	0	0
SPHK1	0.006	0.049	-9999	-0.52	3	3
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.021	0.044	-9999	-0.65	1	1
PLCG1	0.021	0.045	-9999	-0.67	1	1
NHERF/PDGFRB	-0.006	0.042	-9999	-0.3	7	7
YES1	0.002	0.02	-9999	-0.34	1	1
cell migration	-0.006	0.042	-9999	-0.3	7	7
SHC/Grb2/SOS1	0.002	0.016	-9999	-10000	0	0
SLC9A3R2	0.004	0.054	-9999	-0.5	4	4
SLC9A3R1	0.007	0.04	-9999	-0.52	2	2
NHERF1-2/PDGFRB/PTEN	-0.005	0.037	-9999	-0.26	7	7
FYN	0.002	0.02	-9999	-0.34	1	1
DOK1	0.026	0.016	-9999	-0.27	1	1
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0.001	0.066	-9999	-0.5	6	6
RAC1	0.028	0.072	-9999	-0.53	3	3
PRKCD	0.027	0.016	-9999	-0.27	1	1
FER	0.027	0.016	-9999	-0.27	1	1
MAPKKK cascade	-0.001	0.012	-9999	-10000	0	0
RASA1	0.027	0.016	-9999	-0.27	1	1
NCK1	0.01	0	-9999	-10000	0	0
NCK2	0.01	0	-9999	-10000	0	0
p62DOK/Csk	0.006	0.018	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	-0.002	0.027	-9999	-0.36	2	2
chemotaxis	0.017	0.052	-9999	-0.58	1	1
STAT1-3-5/STAT1-3-5	-0.001	0.016	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	-0.001	0.02	-9999	-0.37	1	1
PTPRJ	0.01	0	-9999	-10000	0	0

×

E-cadherin 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
E-cadherin/beta catenin-gamma catenin	-0.003	0.027	-9999	-0.3	3	3
E-cadherin/beta catenin	-0.002	0.027	-9999	-0.36	2	2
CTNNB1	0.01	0	-9999	-10000	0	0
JUP	0.008	0.028	-9999	-0.52	1	1
CDH1	0.007	0.039	-9999	-0.5	2	2

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.01	0	-9999	-10000	0	0
SMAD2	0.011	0	-9999	-10000	0	0
SMAD3	0.033	0	-9999	-10000	0	0
SMAD3/SMAD4	0.036	0.008	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.003	0.027	-9999	-10000	0	0
PPM1A	0.01	0	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
SMAD2/SMAD4	0.016	0	-9999	-10000	0	0
MAP3K1	0.01	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.002	0.027	-9999	-0.36	2	2
MAPK3	0.01	0	-9999	-10000	0	0
MAPK1	0.01	0	-9999	-10000	0	0
NUP214	0.01	0	-9999	-10000	0	0
CTDSP1	0.01	0	-9999	-10000	0	0
CTDSP2	0.01	0	-9999	-10000	0	0
CTDSPL	0.01	0	-9999	-10000	0	0
KPNB1	0.01	0	-9999	-10000	0	0
TGFBRAP1	0.007	0.039	-9999	-0.5	2	2
UBE2I	0.01	0	-9999	-10000	0	0
NUP153	0.01	0	-9999	-10000	0	0
KPNA2	0.002	0.063	-9999	-0.52	5	5
PIAS4	0.01	0	-9999	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.061	0.026	-10000	0	-10000	0	0
CRKL	0.036	0.026	-10000	0	-10000	0	0
mol:DAG	0.041	0.021	-10000	0	-10000	0	0
HRAS	0.053	0.025	-10000	0	-10000	0	0
MAPK8	0.027	0.021	-10000	0	-10000	0	0
RAP1A	0.036	0.026	-10000	0	-10000	0	0
GAB1	0.035	0.029	-10000	0	-10000	0	0
MAPK14	0.027	0.021	-10000	0	-10000	0	0
EPO	0.006	0.04	-10000	0	-0.52	2	2
PLCG1	0.026	0.029	-10000	0	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.012	0.003	-10000	0	-10000	0	0
RAPGEF1	0.01	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.003	0.032	-10000	0	-0.3	4	4
GAB1/SHC/GRB2/SOS1	-0.002	0.02	-10000	0	-10000	0	0
EPO/EPOR (dimer)	0.015	0.029	-10000	0	-0.36	2	2
IRS2	0.035	0.034	-10000	0	-0.44	1	1
STAT1	0.049	0.023	-10000	0	-10000	0	0
STAT5B	0.045	0.022	-10000	0	-10000	0	0
cell proliferation	0.033	0.02	-10000	0	-10000	0	0
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.003	0.027	-10000	0	-0.38	1	1
TEC	0.036	0.026	-10000	0	-10000	0	0
SOCS3	0.007	0.039	-10000	0	-0.5	2	2
STAT1 (dimer)	0.048	0.022	-10000	0	-10000	0	0
JAK2	0.011	0.003	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.04	0.028	-10000	0	-10000	0	0
EPO/EPOR	0.015	0.029	-10000	0	-0.36	2	2
LYN	0.011	0.001	-10000	0	-10000	0	0
TEC/VAV2	0.041	0.028	-10000	0	-10000	0	0
elevation of cytosolic calcium ion concentration	0.012	0.003	-10000	0	-10000	0	0
SHC1	0.01	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.026	0.024	-10000	0	-0.28	2	2
mol:IP3	0.041	0.021	-10000	0	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.004	0.035	-10000	0	-0.4	2	2
SH2B3	0.009	0.039	-10000	0	-0.5	2	2
NFKB1	0.027	0.021	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.001	0.026	0.24	2	-0.21	2	4
PTPN6	0.031	0.027	-10000	0	-10000	0	0
TEC/VAV2/GRB2	-0.003	0.021	-10000	0	-10000	0	0
EPOR	0.012	0.003	-10000	0	-10000	0	0
INPP5D	0.007	0.039	-10000	0	-0.5	2	2
mol:GDP	-0.002	0.02	-10000	0	-10000	0	0
SOS1	0.01	0	-10000	0	-10000	0	0
PLCG2	0.005	0.047	-10000	0	-0.5	3	3
CRKL/CBL/C3G	-0.002	0.019	-10000	0	-10000	0	0
VAV2	0.035	0.029	-10000	0	-10000	0	0
CBL	0.036	0.026	-10000	0	-10000	0	0
SHC/Grb2/SOS1	-0.002	0.019	-10000	0	-10000	0	0
STAT5A	0.044	0.035	-10000	0	-0.5	1	1
GRB2	0.01	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.058	0.035	-10000	0	-0.45	1	1
LYN/PLCgamma2	-0.003	0.033	-10000	0	-0.36	3	3
PTPN11	0.01	0	-10000	0	-10000	0	0
BTK	0.02	0.072	-10000	0	-0.39	3	3
BCL2	0.06	0.034	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.004	0.028	-10000	0	-0.29	2	2
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
AKT2	0.01	0	-10000	0	-10000	0	0
STXBP4	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.032	0.038	0.21	1	-0.32	2	3
YWHAZ	0.01	0	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
YWHAQ	0.01	0	-10000	0	-10000	0	0
TBC1D4	0.018	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.01	0	-10000	0	-10000	0	0
YWHAB	0.01	0	-10000	0	-10000	0	0
SNARE/Synip	0	0	-10000	0	-10000	0	0
YWHAG	0.01	0	-10000	0	-10000	0	0
ASIP	0.004	0.028	-10000	0	-0.52	1	1
PRKCI	0.01	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.01	0	-10000	0	-10000	0	0
GYS1	0.025	0	-10000	0	-10000	0	0
PRKCZ	0.007	0.039	-10000	0	-0.5	2	2
TRIP10	0.01	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	0.034	0.02	-10000	0	-10000	0	0
VAMP2	0.01	0	-10000	0	-10000	0	0
SLC2A4	0.032	0.041	0.21	1	-0.36	2	3
STX4	0.01	0	-10000	0	-10000	0	0
GSK3B	0.02	0	-10000	0	-10000	0	0
SFN	-0.002	0.079	-10000	0	-0.52	8	8
LNPEP	0.01	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.01	0	-10000	0	-10000	0	0
mol:PIP3	-0.001	0.014	-10000	0	-0.27	1	1
FRAP1	0.012	0.003	-10000	0	-10000	0	0
AKT1	-0.001	0.011	-10000	0	-10000	0	0
INSR	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.009	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0.002	-10000	0	-10000	0	0
TSC2	0.01	0	-10000	0	-10000	0	0
RHEB/GDP	-0.001	0.012	-10000	0	-10000	0	0
TSC1	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.012	0.018	-10000	0	-0.32	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0.003	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.022	0.007	-10000	0	-10000	0	0
MAP3K5	0.008	0	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
apoptosis	0.008	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.001	1	1
EIF4B	0.026	0.006	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0	0.004	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.018	0.016	-10000	0	-0.29	1	1
mTOR/RHEB/GTP/Raptor/GBL	0.025	0.008	-10000	0	-10000	0	0
FKBP1A	0.01	0	-10000	0	-10000	0	0
RHEB/GTP	-0.001	0.013	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.001	1	1
FKBP12/Rapamycin	0	0	-10000	0	-10000	0	0
PDPK1	-0.001	0.013	-10000	0	-0.24	1	1
EIF4E	0.01	0	-10000	0	-10000	0	0
ASK1/PP5C	0.017	0.002	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.013	0.008	-10000	0	-10000	0	0
TSC1/TSC2	0	0.009	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.001	1	-10000	0	1
RPS6	0.01	0	-10000	0	-10000	0	0
PPP5C	0.01	0	-10000	0	-10000	0	0
EIF4G1	0.01	0	-10000	0	-10000	0	0
IRS1	0.006	0.019	-10000	0	-0.35	1	1
INS	0	0	-10000	0	-10000	0	0
PTEN	0.009	0	-10000	0	-10000	0	0
PDK2	-0.001	0.013	-10000	0	-0.24	1	1
EIF4EBP1	0.007	0.013	-10000	0	-10000	0	0
PIK3CA	0.01	0	-10000	0	-10000	0	0
PPP2R5D	0.017	0.003	-10000	0	-10000	0	0
peptide biosynthetic process	0.014	0	-10000	0	-10000	0	0
RHEB	0.008	0.028	-10000	0	-0.52	1	1
EIF4A1	0.01	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-10000	0	0
EEF2	0.014	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.012	0.011	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.018	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-9999	-10000	0	0
CDKN1B	0.03	0	-9999	-10000	0	0
CDKN1A	0.029	0.014	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.01	0	-9999	-10000	0	0
FOXO3	0.03	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
BAD	0.01	0	-9999	-10000	0	0
AKT3	0.011	0.03	-9999	-0.32	3	3
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.03	0	-9999	-10000	0	0
AKT1/ASK1	0	0	-9999	-10000	0	0
BAD/YWHAZ	0	0	-9999	-10000	0	0
RICTOR	0.01	0	-9999	-10000	0	0
RAF1	0.01	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
TSC1	0.03	0	-9999	-10000	0	0
YWHAZ	0.01	0	-9999	-10000	0	0
AKT1/RAF1	0.029	0	-9999	-10000	0	0
EP300	0.01	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	0.03	0	-9999	-10000	0	0
YWHAQ	0.01	0	-9999	-10000	0	0
TBC1D4	0.019	0	-9999	-10000	0	0
MAP3K5	0.01	0	-9999	-10000	0	0
MAPKAP1	0.01	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.033	0.014	-9999	-10000	0	0
YWHAH	0.01	0	-9999	-10000	0	0
AKT1S1	0.03	0	-9999	-10000	0	0
CASP9	0.03	0	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.034	0	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
AKT2/p21CIP1	-0.001	0.011	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.014	0.004	-9999	-10000	0	0
CHUK	0.03	0	-9999	-10000	0	0
BAD/BCL-XL	0.039	0	-9999	-10000	0	0
mTORC2	0	0	-9999	-10000	0	0
AKT2	0.014	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.046	0.014	-9999	-10000	0	0
PDPK1	0.01	0	-9999	-10000	0	0
MDM2	0.028	0.02	-9999	-10000	0	0
MAPKKK cascade	-0.029	0	-9999	-10000	0	0
MDM2/Cbp/p300	-0.001	0.016	-9999	-10000	0	0
TSC1/TSC2	0.035	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.015	-9999	-10000	0	0
glucose import	0.02	0.034	-9999	-0.26	5	5
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.025	0.004	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.02	0.034	-9999	-0.26	5	5
GSK3A	0.03	0	-9999	-10000	0	0
FOXO1	0.03	0	-9999	-10000	0	0
GSK3B	0.03	0	-9999	-10000	0	0
SFN	-0.002	0.079	-9999	-0.52	8	8
G1/S transition of mitotic cell cycle	0.035	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.036	0.019	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
KPNA1	0.01	0	-9999	-10000	0	0
HSP90AA1	0.01	0	-9999	-10000	0	0
YWHAG	0.01	0	-9999	-10000	0	0
RHEB	0.008	0.028	-9999	-0.52	1	1
CREBBP	0.01	0	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.022	0.031	-9999	-0.31	3	3
CRKL	0.01	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.01	0	-9999	-10000	0	0
ITGA4	0.007	0.039	-9999	-0.5	2	2
alpha4/beta7 Integrin/MAdCAM1	-0.005	0.035	-9999	-0.27	3	3
EPO	0.003	0.04	-9999	-0.52	2	2
alpha4/beta7 Integrin	-0.003	0.033	-9999	-0.36	3	3
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.002	0.027	-9999	-0.36	2	2
EPO/EPOR (dimer)	-0.002	0.028	-9999	-0.37	2	2
lamellipodium assembly	0	0.003	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
JAK2	-0.002	0.021	-9999	-10000	0	0
PXN	0.01	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
MADCAM1	0.004	0.049	-9999	-0.52	3	3
cell adhesion	-0.005	0.034	-9999	-0.27	3	3
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0.01	0	-9999	-10000	0	0
SRC	0.022	0.037	-9999	-0.27	1	1
ITGB7	0.008	0.027	-9999	-0.5	1	1
RAC1	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.005	0.038	-9999	-0.3	6	6
p130Cas/Crk/Dock1	-0.004	0.029	-9999	-10000	0	0
VCAM1	0.004	0.055	-9999	-0.51	4	4
RHOA	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.001	0.02	-9999	-10000	0	0
BCAR1	0.027	0.038	-9999	-10000	0	0
EPOR	0.01	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
Rac1/GTP	0	0.003	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.031	0.047	-9999	-10000	0	0
BAG4	0.01	0	-9999	-10000	0	0
BAD	0.023	0.02	-9999	-10000	0	0
NFKBIA	0.01	0	-9999	-10000	0	0
BIRC3	0.001	0.068	-9999	-0.52	6	6
BAX	0.023	0.02	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.01	0.015	-9999	-10000	0	0
IKBKB	0.036	0.045	-9999	-10000	0	0
MAP2K2	0.032	0.022	-9999	-10000	0	0
MAP2K1	0.032	0.022	-9999	-10000	0	0
SMPD1	0.015	0.015	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.036	0.046	-9999	-10000	0	0
MAP2K4	0.028	0.02	-9999	-10000	0	0
protein ubiquitination	0.037	0.045	-9999	-10000	0	0
EnzymeConsortium:2.7.1.37	0.036	0.025	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
RAF1	0.028	0.022	-9999	-10000	0	0
CRADD	0.009	0.028	-9999	-0.52	1	1
mol:ceramide	0.017	0.02	-9999	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-9999	-10000	0	0
MADD	0.01	0	-9999	-10000	0	0
MAP3K1	0.023	0.02	-9999	-10000	0	0
TRADD	0.01	0	-9999	-10000	0	0
RELA/p50	0.01	0	-9999	-10000	0	0
MAPK3	0.034	0.022	-9999	-10000	0	0
MAPK1	0.034	0.022	-9999	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-9999	-10000	0	0
FADD	0.031	0.047	-9999	-10000	0	0
KSR1	0.023	0.021	-9999	-10000	0	0
MAPK8	0.033	0.019	-9999	-10000	0	0
TRAF2	0.01	0	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.036	0.045	-9999	-10000	0	0
TNF R/SODD	0	0	-9999	-10000	0	0
TNF	-0.015	0.11	-9999	-0.51	17	17
CYCS	0.024	0.02	-9999	-10000	0	0
IKBKG	0.036	0.045	-9999	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.026	0.049	-9999	-0.25	2	2
RELA	0.01	0	-9999	-10000	0	0
RIPK1	0.01	0	-9999	-10000	0	0
AIFM1	0.024	0.02	-9999	-10000	0	0
TNF/TNF R/SODD	-0.014	0.063	-9999	-0.3	17	17
TNFRSF1A	0.01	0	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.021	0.014	-9999	-10000	0	0
NSMAF	0.031	0.046	-9999	-10000	0	0
response to hydrogen peroxide	0	0	-9999	-10000	0	0
BCL2	0.007	0.04	-9999	-0.52	2	2

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.01	0	-9999	-10000	0	0
Rac1/GDP	0	0.003	-9999	-10000	0	0
DOCK1	0.01	0	-9999	-10000	0	0
ITGA4	0.007	0.039	-9999	-0.5	2	2
RAC1	0.01	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.003	0.033	-9999	-0.36	3	3
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.002	0.022	-9999	-0.29	2	2
alpha4/beta7 Integrin/Paxillin	-0.002	0.024	-9999	-0.26	3	3
lamellipodium assembly	0	0.013	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
TLN1	0.008	0.027	-9999	-0.5	1	1
PXN	0.018	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
ARF6/GTP	-0.001	0.016	-9999	-10000	0	0
cell adhesion	-0.002	0.022	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.001	0.02	-9999	-10000	0	0
ITGB1	0.01	0	-9999	-10000	0	0
ITGB7	0.008	0.027	-9999	-0.5	1	1
ARF6/GDP	0	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.004	0.031	-9999	-10000	0	0
p130Cas/Crk/Dock1	-0.001	0.016	-9999	-0.29	1	1
VCAM1	0.004	0.055	-9999	-0.51	4	4
alpha4/beta1 Integrin/Paxillin/Talin	-0.002	0.022	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.001	0.018	-9999	-10000	0	0
BCAR1	0.008	0.027	-9999	-0.5	1	1
mol:GDP	0.001	0.018	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GIT1	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.002	0.022	-9999	-10000	0	0
Rac1/GTP	0	0.014	-9999	-10000	0	0

×

Atypical NF-kappaB 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
BCL3/RelA	-0.001	0.019	-9999	-0.36	1	1
FBXW11	0.01	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.021	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.035	0.021	-9999	-10000	0	0
NFKBIA	0.021	0.024	-9999	-10000	0	0
MAPK14	0.01	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.021	0	-9999	-10000	0	0
ARRB2	0.014	0	-9999	-10000	0	0
REL	0.01	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.02	0.017	-9999	-0.29	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.021	0	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.016	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
NFKB1	0.018	0	-9999	-10000	0	0
RELA	0.01	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.026	0.024	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.038	0.021	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.026	0.024	-9999	-10000	0	0
IKBKB	0.01	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-9999	-10000	0	0
SYK	0.005	0.047	-9999	-0.5	3	3
I kappa B alpha/PIK3R1	0.025	0.023	-9999	-10000	0	0
cell death	-0.002	0.016	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.021	0	-9999	-10000	0	0
LCK	0.007	0.039	-9999	-0.51	2	2
BCL3	0.008	0.027	-9999	-0.5	1	1

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.002	0.019	-9999	-10000	0	0
MDM2/SUMO1	-0.001	0.019	-9999	-0.25	2	2
HDAC4	0.008	0.028	-9999	-0.52	1	1
Ran/GTP/Exportin 1/HDAC1	-0.001	0.016	-9999	-10000	0	0
SUMO1	0.01	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.023	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.007	0.04	-9999	-0.52	2	2
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
SUMO1/HDAC4	-0.001	0.013	-9999	-0.25	1	1
SUMO1/HDAC1	0	0	-9999	-10000	0	0
RANGAP1	0.01	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	-0.002	0.02	-9999	-0.27	2	2
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.017	0	-9999	-10000	0	0
Ran/GTP	-0.001	0.018	-9999	-0.24	2	2
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.007	0.04	-9999	-0.52	2	2
UBE2I	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	-0.001	0.017	-9999	-0.23	2	2
NPC	0	0	-9999	-10000	0	0
PIAS2	0.01	0	-9999	-10000	0	0
PIAS1	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.039	0.012	-9999	-10000	0	0
adherens junction organization	0.032	0.027	-9999	-0.22	2	2
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	0.036	0.043	-9999	-10000	0	0
FMN1	0.024	0.052	-9999	-10000	0	0
mol:IP3	-0.001	0.009	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.028	0.021	-9999	-0.23	2	2
CTNNB1	0.01	0.001	-9999	-10000	0	0
AKT1	0.038	0.014	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.029	0.032	-9999	-0.36	2	2
CTNND1	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.033	0.02	-9999	-10000	0	0
VASP	0.034	0.02	-9999	-10000	0	0
ZYX	0.034	0.02	-9999	-10000	0	0
JUB	0.033	0.024	-9999	-10000	0	0
EGFR(dimer)	0.025	0.049	-9999	-0.33	1	1
E-cadherin/beta catenin-gamma catenin	-0.002	0.027	-9999	-0.29	3	3
mol:PI-3-4-5-P3	-0.001	0.012	-9999	-10000	0	0
PIK3CA	0.01	0	-9999	-10000	0	0
PI3K	-0.001	0.012	-9999	-10000	0	0
FYN	0.026	0.056	-9999	-10000	0	0
mol:Ca2+	-0.001	0.009	-9999	-10000	0	0
JUP	0.008	0.028	-9999	-0.52	1	1
PIK3R1	0.01	0	-9999	-10000	0	0
mol:DAG	-0.001	0.009	-9999	-10000	0	0
CDH1	0.007	0.038	-9999	-0.5	2	2
RhoA/GDP	0.036	0.043	-9999	-10000	0	0
establishment of polarity of embryonic epithelium	0.033	0.02	-9999	-10000	0	0
SRC	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
EGFR	-0.005	0.087	-9999	-0.52	10	10
CASR	0.016	0.07	-9999	-10000	0	0
RhoA/GTP	-0.001	0.008	-9999	-10000	0	0
AKT2	0.038	0.014	-9999	-10000	0	0
actin cable formation	0.03	0.05	-9999	-10000	0	0
apoptosis	0.001	0.01	-9999	-10000	0	0
CTNNA1	0.011	0	-9999	-10000	0	0
mol:GDP	0.032	0.045	-9999	-0.3	1	1
PIP5K1A	0.034	0.02	-9999	-10000	0	0
PLCG1	-0.001	0.009	-9999	-10000	0	0
Rac1/GTP	-0.007	0.039	-9999	-0.3	1	1
homophilic cell adhesion	0.001	0	-9999	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.016	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	0.01	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.02	0	-9999	-10000	0	0
CD4	0.001	0.066	-9999	-0.5	6	6
CLTA	0.01	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.009	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	0.022	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.01	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0	0	-9999	-10000	0	0
AP2M1	0.01	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	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.021	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0.01	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0.01	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.022	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	0.01	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	0.025	0.029	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.009	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	0.009	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	-0.005	0.038	-9999	-0.29	6	6

×

Alternative NF-kappaB pathway

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	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0	-9999	-9999
FBXW11	0.01	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.01	-9999	-9999
CHUK	0.01	-9999	-9999
NF kappa B2 p100/RelB	0	-9999	-9999
NFKB1	0.01	-9999	-9999
MAP3K14	0.01	-9999	-9999
NF kappa B1 p50/RelB	0	-9999	-9999
RELB	0.01	-9999	-9999
NFKB2	0.01	-9999	-9999
NF kappa B2 p52/RelB	0	-9999	-9999
regulation of B cell activation	0	-9999	-9999

pid_entity	TCGA.J2.8194	TCGA.J2.8192	TCGA.99.8033	TCGA.99.8032
109_MAP3K5	0.043	0.043	0.043	0.043
47_PPARGC1A	0.0097	0.0097	0.0097	0.0097
105_BMP4	0.0097	0.0097	0.0097	0.0097
105_BMP6	0.0097	0.0097	0.0097	0.0097
105_BMP7	0.0097	0.0097	-0.5	0.0097
105_BMP2	0.0097	0.0097	0.0097	0.0097
131_RELN/VLDLR	0	0	0	0
30_TGFB1/TGF beta receptor Type II	0.0095	0.0092	0.0093	0.014
84_STAT5B	-0.031	-0.031	-0.011	0.024
84_STAT5A	-0.031	-0.031	-0.011	0.024