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

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	195
Syndecan-1-mediated signaling events	152
Reelin signaling pathway	116
Lissencephaly gene (LIS1) in neuronal migration and development	70
IL4-mediated signaling events	68
FOXA2 and FOXA3 transcription factor networks	62
Glypican 1 network	62
Ephrin A reverse signaling	60
Osteopontin-mediated events	55
IL23-mediated signaling events	55

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
TCGA08_retinoblastoma	0.4267	195	1562	8	-0.16	0.12	1000	-1000	-0.013	-1000
Syndecan-1-mediated signaling events	0.3326	152	5190	34	-0.7	0.012	1000	-1000	-0.062	-1000
Reelin signaling pathway	0.2538	116	6537	56	-0.55	0.035	1000	-1000	-0.082	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1532	70	3784	54	-0.53	0.024	1000	-1000	-0.099	-1000
IL4-mediated signaling events	0.1488	68	6278	91	-0.84	0.61	1000	-1000	-0.18	-1000
FOXA2 and FOXA3 transcription factor networks	0.1357	62	2870	46	-0.72	0.02	1000	-1000	-0.14	-1000
Glypican 1 network	0.1357	62	3008	48	-0.29	0.025	1000	-1000	-0.042	-1000
Ephrin A reverse signaling	0.1313	60	420	7	-0.079	0	1000	-1000	-0.026	-1000
Osteopontin-mediated events	0.1204	55	2106	38	-0.34	0.019	1000	-1000	-0.1	-1000
IL23-mediated signaling events	0.1204	55	3343	60	-0.5	0.012	1000	-1000	-0.2	-1000
BCR signaling pathway	0.1160	53	5339	99	-0.24	0.013	1000	-1000	-0.1	-1000
Syndecan-4-mediated signaling events	0.1072	49	3328	67	-0.43	0.045	1000	-1000	-0.075	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.1050	48	3768	78	-0.18	0.075	1000	-1000	-0.091	-1000
Endothelins	0.0919	42	4045	96	-0.37	0.088	1000	-1000	-0.094	-1000
Fc-epsilon receptor I signaling in mast cells	0.0832	38	3780	97	-0.16	0.033	1000	-1000	-0.091	-1000
Glucocorticoid receptor regulatory network	0.0810	37	4228	114	-0.64	0.3	1000	-1000	-0.08	-1000
HIF-1-alpha transcription factor network	0.0788	36	2801	76	-0.72	0.019	1000	-1000	-0.2	-1000
Visual signal transduction: Rods	0.0788	36	1896	52	-0.26	0.012	1000	-1000	-0.074	-1000
Syndecan-2-mediated signaling events	0.0766	35	2449	69	-0.42	0.037	1000	-1000	-0.035	-1000
Presenilin action in Notch and Wnt signaling	0.0744	34	2105	61	-0.47	0.2	1000	-1000	-0.069	-1000
BMP receptor signaling	0.0744	34	2786	81	-0.28	0.045	1000	-1000	-0.099	-1000
Ephrin B reverse signaling	0.0744	34	1639	48	-0.18	0.08	1000	-1000	-0.065	-1000
IL1-mediated signaling events	0.0700	32	2030	62	-0.24	0.018	1000	-1000	-0.11	-1000
Signaling events mediated by the Hedgehog family	0.0678	31	1635	52	-0.11	0.11	1000	-1000	-0.061	-1000
Calcium signaling in the CD4+ TCR pathway	0.0678	31	970	31	-0.47	0.012	1000	-1000	-0.062	-1000
Caspase cascade in apoptosis	0.0656	30	2264	74	-0.14	0.06	1000	-1000	-0.05	-1000
Effects of Botulinum toxin	0.0635	29	768	26	-0.096	0.016	1000	-1000	-0.063	-1000
JNK signaling in the CD4+ TCR pathway	0.0613	28	489	17	-0.11	0.012	1000	-1000	-0.045	-1000
TCGA08_p53	0.0613	28	201	7	-0.12	0.058	1000	-1000	-0.019	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0613	28	1951	68	-0.52	0.058	1000	-1000	-0.12	-1000
p75(NTR)-mediated signaling	0.0591	27	3460	125	-0.84	0.036	1000	-1000	-0.11	-1000
amb2 Integrin signaling	0.0591	27	2253	82	-0.13	0.017	1000	-1000	-0.07	-1000
Syndecan-3-mediated signaling events	0.0591	27	945	35	-0.42	0.036	1000	-1000	-0.043	-1000
Canonical Wnt signaling pathway	0.0591	27	1424	51	-0.47	0.21	1000	-1000	-0.069	-1000
Ras signaling in the CD4+ TCR pathway	0.0569	26	456	17	-0.089	0.023	1000	-1000	-0.055	-1000
Visual signal transduction: Cones	0.0503	23	902	38	-0.13	0.012	1000	-1000	-0.043	-1000
Signaling events regulated by Ret tyrosine kinase	0.0503	23	1961	82	-0.16	0.012	1000	-1000	-0.087	-1000
Wnt signaling	0.0503	23	167	7	-0.13	0.012	1000	-1000	-0.042	-1000
TCR signaling in naïve CD8+ T cells	0.0481	22	2079	93	-0.085	0.047	1000	-1000	-0.093	-1000
EPHB forward signaling	0.0481	22	1926	85	-0.18	0.086	1000	-1000	-0.092	-1000
LPA4-mediated signaling events	0.0460	21	259	12	-0.1	0.016	1000	-1000	-0.028	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0460	21	1920	88	-0.23	0.066	1000	-1000	-0.11	-1000
Signaling events mediated by PRL	0.0460	21	727	34	-0.11	0.054	1000	-1000	-0.041	-1000
IL12-mediated signaling events	0.0438	20	1801	87	-0.2	0.03	1000	-1000	-0.15	-1000
Plasma membrane estrogen receptor signaling	0.0438	20	1803	86	-0.16	0.053	1000	-1000	-0.08	-1000
LPA receptor mediated events	0.0394	18	1915	102	-0.21	0.021	1000	-1000	-0.093	-1000
EGFR-dependent Endothelin signaling events	0.0394	18	382	21	-0.089	0.018	1000	-1000	-0.072	-1000
a4b1 and a4b7 Integrin signaling	0.0372	17	88	5	-0.007	0.006	1000	-1000	-0.024	-1000
Nectin adhesion pathway	0.0372	17	1117	63	-0.67	0.04	1000	-1000	-0.073	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0372	17	887	52	-0.24	0.027	1000	-1000	-0.047	-1000
HIF-2-alpha transcription factor network	0.0372	17	755	43	-0.38	0.17	1000	-1000	-0.086	-1000
Signaling mediated by p38-alpha and p38-beta	0.0372	17	762	44	-0.04	0.012	1000	-1000	-0.039	-1000
Thromboxane A2 receptor signaling	0.0328	15	1586	105	-0.24	0.073	1000	-1000	-0.067	-1000
Noncanonical Wnt signaling pathway	0.0306	14	374	26	-0.13	0.012	1000	-1000	-0.065	-1000
Glypican 2 network	0.0306	14	57	4	-0.012	-0.005	1000	-1000	-0.02	-1000
Regulation of nuclear SMAD2/3 signaling	0.0284	13	1796	136	-0.49	0.087	1000	-1000	-0.073	-1000
Arf6 signaling events	0.0284	13	820	62	-0.14	0.03	1000	-1000	-0.051	-1000
Signaling events mediated by HDAC Class III	0.0284	13	553	40	-0.17	0.023	1000	-1000	-0.028	-1000
IL6-mediated signaling events	0.0284	13	989	75	-0.14	0.051	1000	-1000	-0.085	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0284	13	1608	120	-0.15	0.12	1000	-1000	-0.073	-1000
ErbB4 signaling events	0.0263	12	888	69	-0.29	0.061	1000	-1000	-0.1	-1000
Signaling events mediated by PTP1B	0.0263	12	920	76	-0.36	0.056	1000	-1000	-0.087	-1000
S1P5 pathway	0.0263	12	210	17	-0.11	0.034	1000	-1000	-0.039	-1000
S1P1 pathway	0.0263	12	440	36	-0.11	0.014	1000	-1000	-0.059	-1000
FAS signaling pathway (CD95)	0.0263	12	587	47	-0.072	0.028	1000	-1000	-0.053	-1000
Retinoic acid receptors-mediated signaling	0.0263	12	707	58	-0.24	0.024	1000	-1000	-0.076	-1000
IGF1 pathway	0.0263	12	692	57	-0.1	0.025	1000	-1000	-0.097	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0241	11	335	28	-0.11	0.021	1000	-1000	-0.037	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0241	11	419	37	-0.2	0.032	1000	-1000	-0.046	-1000
Integrins in angiogenesis	0.0241	11	1004	84	-0.34	0.031	1000	-1000	-0.093	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0241	11	383	33	-0.15	0.036	1000	-1000	-0.05	-1000
S1P4 pathway	0.0241	11	280	25	-0.11	0.022	1000	-1000	-0.039	-1000
Aurora A signaling	0.0219	10	611	60	-0.23	0.036	1000	-1000	-0.047	-1000
IL27-mediated signaling events	0.0219	10	527	51	-0.16	0.021	1000	-1000	-0.078	-1000
Regulation of Androgen receptor activity	0.0219	10	739	70	-0.25	0.026	1000	-1000	-0.071	-1000
Nongenotropic Androgen signaling	0.0197	9	489	52	-0.11	0.03	1000	-1000	-0.055	-1000
S1P3 pathway	0.0197	9	387	42	-0.11	0.025	1000	-1000	-0.047	-1000
Coregulation of Androgen receptor activity	0.0175	8	655	76	-0.19	0.046	1000	-1000	-0.036	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0175	8	285	34	-0.006	0.021	1000	-1000	-0.054	-1000
Signaling mediated by p38-gamma and p38-delta	0.0175	8	126	15	-0.039	0.023	1000	-1000	-0.029	-1000
Regulation of Telomerase	0.0175	8	876	102	-0.36	0.042	1000	-1000	-0.12	-1000
Cellular roles of Anthrax toxin	0.0153	7	279	39	-0.045	0.014	1000	-1000	-0.023	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0153	7	645	83	-0.24	0.06	1000	-1000	-0.08	-1000
Class I PI3K signaling events	0.0153	7	583	73	-0.16	0.032	1000	-1000	-0.064	-1000
IFN-gamma pathway	0.0131	6	435	68	-0.064	0.032	1000	-1000	-0.1	-1000
FoxO family signaling	0.0131	6	437	64	-0.12	0.079	1000	-1000	-0.084	-1000
PDGFR-beta signaling pathway	0.0131	6	640	97	-0.19	0.045	1000	-1000	-0.086	-1000
Aurora B signaling	0.0131	6	464	67	-0.34	0.06	1000	-1000	-0.07	-1000
ErbB2/ErbB3 signaling events	0.0109	5	360	65	-0.05	0.032	1000	-1000	-0.076	-1000
PDGFR-alpha signaling pathway	0.0109	5	221	44	-0.018	0.025	1000	-1000	-0.074	-1000
Ceramide signaling pathway	0.0109	5	389	76	-0.1	0.044	1000	-1000	-0.05	-1000
Regulation of p38-alpha and p38-beta	0.0109	5	312	54	-0.16	0.031	1000	-1000	-0.062	-1000
Rapid glucocorticoid signaling	0.0109	5	111	20	-0.014	0.012	1000	-1000	-0.025	-1000
FOXM1 transcription factor network	0.0109	5	261	51	-0.16	0.15	1000	-1000	-0.22	-1000
Signaling events mediated by HDAC Class II	0.0088	4	330	75	-0.053	0.03	1000	-1000	-0.044	-1000
Hedgehog signaling events mediated by Gli proteins	0.0088	4	272	65	-0.11	0.051	1000	-1000	-0.07	-1000
TCGA08_rtk_signaling	0.0088	4	125	26	-0.057	0.039	1000	-1000	-0.021	-1000
Class IB PI3K non-lipid kinase events	0.0088	4	12	3	-0.008	0.008	1000	-1000	-0.018	-1000
EPO signaling pathway	0.0066	3	202	55	-0.032	0.047	1000	-1000	-0.097	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0066	3	279	74	-0.1	0.065	1000	-1000	-0.088	-1000
Arf6 trafficking events	0.0066	3	220	71	-0.039	0.035	1000	-1000	-0.077	-1000
VEGFR1 specific signals	0.0066	3	170	56	-0.028	0.043	1000	-1000	-0.062	-1000
E-cadherin signaling in keratinocytes	0.0066	3	155	43	-0.099	0.046	1000	-1000	-0.058	-1000
PLK2 and PLK4 events	0.0044	2	8	3	0.006	0.014	1000	-1000	-0.021	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0044	2	173	85	-0.015	0.051	1000	-1000	-0.07	-1000
PLK1 signaling events	0.0044	2	217	85	-0.031	0.031	1000	-1000	-0.045	-1000
TRAIL signaling pathway	0.0044	2	123	48	-0.033	0.041	1000	-1000	-0.065	-1000
Paxillin-dependent events mediated by a4b1	0.0044	2	95	36	-0.026	0.027	1000	-1000	-0.066	-1000
IL2 signaling events mediated by PI3K	0.0044	2	144	58	-0.058	0.056	1000	-1000	-0.09	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0044	2	127	45	-0.019	0.057	1000	-1000	-0.091	-1000
IL2 signaling events mediated by STAT5	0.0044	2	63	22	0	0.057	1000	-1000	-0.066	-1000
Insulin Pathway	0.0044	2	187	74	-0.041	0.033	1000	-1000	-0.1	-1000
p38 MAPK signaling pathway	0.0044	2	94	44	-0.027	0.034	1000	-1000	-0.068	-1000
Arf6 downstream pathway	0.0022	1	75	43	-0.028	0.03	1000	-1000	-0.032	-1000
ceramide signaling pathway	0.0022	1	66	49	-0.009	0.045	1000	-1000	-0.059	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0022	1	141	125	-0.002	0.075	1000	-1000	-0.11	-1000
E-cadherin signaling in the nascent adherens junction	0.0022	1	122	76	-0.03	0.051	1000	-1000	-0.087	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	6	23	0.01	0.039	1000	-1000	-0.054	-1000
Canonical NF-kappaB pathway	0.0000	0	38	39	-0.007	0.067	1000	-1000	-0.094	-1000
BARD1 signaling events	0.0000	0	17	57	-0.031	0.061	1000	-1000	-0.07	-1000
Circadian rhythm pathway	0.0000	0	19	22	-0.012	0.043	1000	-1000	-0.048	-1000
Aurora C signaling	0.0000	0	2	7	0	0.022	1000	-1000	-0.035	-1000
Insulin-mediated glucose transport	0.0000	0	20	32	-0.001	0.039	1000	-1000	-0.053	-1000
mTOR signaling pathway	0.0000	0	26	53	-0.001	0.034	1000	-1000	-0.06	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	18	68	-0.037	0.05	1000	-1000	-0.054	-1000
Signaling events mediated by HDAC Class I	0.0000	0	64	104	-0.025	0.047	1000	-1000	-0.066	-1000
Atypical NF-kappaB pathway	0.0000	0	9	31	-0.001	0.041	1000	-1000	-0.045	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	12	27	0	0.03	1000	-1000	-0.054	-1000
E-cadherin signaling events	0.0000	0	1	5	0.011	0.025	1000	-1000	-0.023	-1000
Arf1 pathway	0.0000	0	33	54	-0.004	0.022	1000	-1000	-0.032	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.037	1000	-1000	-0.038	-1000
Total	NA	2536	139704	7203	-24	6.4	131000	-131000	-9.1	-131000

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.15	0.2	-10000	0	-0.4	183	183
CDKN2C	0.023	0.033	-10000	0	-10000	0	0
CDKN2A	-0.16	0.31	-10000	0	-0.75	101	101
CCND2	0.11	0.11	0.2	254	-10000	0	254
RB1	-0.11	0.12	-10000	0	-0.2	256	256
CDK4	0.12	0.12	0.21	256	-10000	0	256
CDK6	0.12	0.12	0.22	256	-10000	0	256
G1/S progression	0.11	0.12	0.2	256	-10000	0	256

×

Syndecan-1-mediated signaling events

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
TGFB1	0.011	0.035	-9999	-0.73	1	1
CCL5	-0.007	0.092	-9999	-0.44	20	20
SDCBP	0.01	0.03	-9999	-0.44	2	2
FGFR/FGF2/Syndecan-1	-0.33	0.14	-9999	-0.42	302	302
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.32	0.14	-9999	-0.4	305	305
Syndecan-1/Syntenin	-0.31	0.13	-9999	-0.4	302	302
MAPK3	-0.28	0.12	-9999	-0.51	33	33
HGF/MET	0.005	0.077	-9999	-0.41	14	14
TGFB1/TGF beta receptor Type II	0.011	0.035	-9999	-0.73	1	1
BSG	0.011	0.021	-9999	-0.44	1	1
keratinocyte migration	-0.31	0.13	-9999	-0.4	305	305
Syndecan-1/RANTES	-0.32	0.13	-9999	-0.4	314	314
Syndecan-1/CD147	-0.3	0.13	-9999	-0.38	302	302
Syndecan-1/Syntenin/PIP2	-0.3	0.13	-9999	-0.39	302	302
LAMA5	0.005	0.072	-9999	-0.67	5	5
positive regulation of cell-cell adhesion	-0.3	0.13	-9999	-0.38	302	302
MMP7	-0.7	0.14	-9999	-0.73	439	439
HGF	0.003	0.068	-9999	-0.47	9	9
Syndecan-1/CASK	-0.32	0.13	-9999	-0.4	302	302
Syndecan-1/HGF/MET	-0.3	0.13	-9999	-0.38	311	311
regulation of cell adhesion	-0.26	0.12	-9999	-0.49	32	32
HPSE	0.007	0.047	-9999	-0.44	5	5
positive regulation of cell migration	-0.33	0.14	-9999	-0.42	302	302
SDC1	-0.33	0.14	-9999	-0.42	302	302
Syndecan-1/Collagen	-0.33	0.14	-9999	-0.42	302	302
PPIB	0.012	0	-9999	-10000	0	0
MET	0.004	0.077	-9999	-0.73	5	5
PRKACA	0.012	0	-9999	-10000	0	0
MMP9	-0.051	0.2	-9999	-0.71	40	40
MAPK1	-0.28	0.12	-9999	-0.51	32	32
homophilic cell adhesion	-0.33	0.14	-9999	-0.42	302	302
MMP1	-0.47	0.36	-9999	-0.73	296	296

×

Reelin signaling pathway

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
CDK5R1/CDK5	0.017	0.027	-9999	-0.55	1	1
VLDLR	-0.029	0.13	-9999	-0.44	42	42
CRKL	0.012	0	-9999	-10000	0	0
LRPAP1	0.012	0	-9999	-10000	0	0
FYN	0.012	0	-9999	-10000	0	0
ITGA3	0.011	0.021	-9999	-0.44	1	1
RELN/VLDLR/Fyn	-0.11	0.16	-9999	-0.48	30	30
MAPK8IP1/MKK7/MAP3K11/JNK1	0.035	0.031	-9999	-0.62	1	1
AKT1	-0.11	0.15	-9999	-0.42	48	48
MAP2K7	0.011	0.021	-9999	-0.44	1	1
RAPGEF1	0.011	0.021	-9999	-0.44	1	1
DAB1	-0.063	0.22	-9999	-0.73	45	45
RELN/LRP8/DAB1	-0.45	0.26	-9999	-0.57	350	350
LRPAP1/LRP8	-0.4	0.25	-9999	-0.55	335	335
RELN/LRP8/DAB1/Fyn	-0.42	0.24	-9999	-0.53	350	350
DAB1/alpha3/beta1 Integrin	-0.4	0.23	-9999	-0.63	183	183
long-term memory	-0.55	0.31	-9999	-0.76	268	268
DAB1/LIS1	-0.41	0.25	-9999	-0.52	355	355
DAB1/CRLK/C3G	-0.4	0.23	-9999	-0.63	183	183
PIK3CA	0.012	0.001	-9999	-10000	0	0
DAB1/NCK2	-0.42	0.25	-9999	-0.61	225	225
ARHGEF2	0.012	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.11	0.2	-9999	-0.44	118	118
CDK5R1	0.011	0.035	-9999	-0.73	1	1
RELN	-0.18	0.22	-9999	-0.44	196	196
PIK3R1	0.012	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.44	0.25	-9999	-0.57	335	335
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.47	0.27	-9999	-0.58	362	362
MAPK8	0.012	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.15	0.2	-9999	-0.5	73	73
ITGB1	0.012	0	-9999	-10000	0	0
MAP1B	-0.42	0.25	-9999	-0.52	357	357
RELN/LRP8	-0.44	0.25	-9999	-0.57	335	335
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.52	0.3	-9999	-0.63	371	371
PI3K	0.018	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.018	0.015	-9999	-0.3	1	1
RAP1A	-0.37	0.23	-9999	-0.59	183	183
PAFAH1B1	0.012	0	-9999	-10000	0	0
MAPK8IP1	0.011	0.021	-9999	-0.44	1	1
CRLK/C3G	0.018	0.015	-9999	-0.3	1	1
GRIN2B	-0.18	0.32	-9999	-0.73	118	118
NCK2	0.012	0	-9999	-10000	0	0
neuron differentiation	-0.2	0.14	-9999	-0.35	175	175
neuron adhesion	-0.35	0.22	-9999	-0.56	183	183
LRP8	-0.53	0.33	-9999	-0.73	335	335
GSK3B	-0.096	0.14	-9999	-0.4	48	48
RELN/VLDLR/DAB1/Fyn	-0.13	0.19	-9999	-0.47	73	73
MAP3K11	0.011	0.021	-9999	-0.44	1	1
RELN/VLDLR/DAB1/P13K	-0.12	0.16	-9999	-0.45	48	48
CDK5	0.012	0	-9999	-10000	0	0
MAPT	-0.066	0.17	-9999	-0.39	98	98
neuron migration	-0.32	0.2	-9999	-0.52	189	189
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.2	0.14	-9999	-0.35	175	175
RELN/VLDLR	-0.42	0.25	-9999	-0.54	341	341

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.012	0	-9999	-10000	0	0
VLDLR	-0.029	0.13	-9999	-0.44	42	42
LRPAP1	0.012	0	-9999	-10000	0	0
NUDC	0.012	0	-9999	-10000	0	0
RELN/LRP8	-0.44	0.25	-9999	-0.57	335	335
CaM/Ca2+	0.009	0	-9999	-10000	0	0
KATNA1	0.012	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.4	0.23	-9999	-0.52	335	335
IQGAP1/CaM	0.018	0	-9999	-10000	0	0
DAB1	-0.063	0.22	-9999	-0.73	45	45
IQGAP1	0.012	0	-9999	-10000	0	0
PLA2G7	0.007	0.047	-9999	-0.44	5	5
CALM1	0.012	0	-9999	-10000	0	0
DYNLT1	0.012	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.4	0.25	-9999	-0.55	335	335
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.011	0.021	-9999	-0.44	1	1
CDK5R1	0.011	0.035	-9999	-0.73	1	1
LIS1/Poliovirus Protein 3A	0.014	0	-9999	-10000	0	0
CDK5R2	-0.036	0.14	-9999	-0.46	45	45
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.16	0.21	-9999	-0.55	73	73
YWHAE	0.012	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.32	0.19	-9999	-0.51	167	167
MAP1B	-0.006	0.038	-9999	-0.26	10	10
RAC1	0.019	0	-9999	-10000	0	0
p35/CDK5	-0.35	0.21	-9999	-0.54	172	172
RELN	-0.18	0.22	-9999	-0.44	196	196
PAFAH/LIS1	0.021	0.028	-9999	-10000	0	0
LIS1/CLIP170	0.023	0.013	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.25	0.14	-9999	-0.4	167	167
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.12	0.17	-9999	-0.47	53	53
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.34	0.2	-9999	-0.55	167	167
LIS1/IQGAP1	0.024	0	-9999	-10000	0	0
RHOA	0.019	0	-9999	-10000	0	0
PAFAH1B1	0.019	0	-9999	-10000	0	0
PAFAH1B3	0.001	0.091	-9999	-0.73	7	7
PAFAH1B2	0.012	0.001	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.019	0.026	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.3	0.19	-9999	-0.49	167	167
LRP8	-0.53	0.33	-9999	-0.73	335	335
NDEL1/Katanin 60	-0.32	0.19	-9999	-0.51	167	167
P39/CDK5	-0.37	0.22	-9999	-0.54	209	209
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.024	0	-9999	-10000	0	0
CDK5	-0.37	0.22	-9999	-0.49	335	335
PPP2R5D	0.012	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.02	0.011	-9999	-10000	0	0
CSNK2A1	0.012	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.13	0.19	-9999	-0.47	73	73
RELN/VLDLR	-0.42	0.25	-9999	-0.54	341	341
CDC42	0.018	0.018	-9999	-0.36	1	1

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.54	0.5	-10000	0	-1.2	120	120
STAT6 (cleaved dimer)	-0.62	0.51	-10000	0	-1.1	191	191
IGHG1	-0.18	0.16	-10000	0	-0.44	1	1
IGHG3	-0.53	0.48	-10000	0	-1.1	138	138
AKT1	-0.28	0.27	-10000	0	-0.66	73	73
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.22	0.21	-10000	0	-0.53	55	55
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.27	0.24	-10000	0	-0.63	38	38
THY1	-0.55	0.52	-10000	0	-1.2	121	121
MYB	0.011	0.021	-10000	0	-0.44	1	1
HMGA1	0.011	0.035	-10000	0	-0.73	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.39	0.35	-10000	0	-0.8	145	145
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.27	0.25	-10000	0	-0.64	38	38
SP1	0.017	0.009	-10000	0	-10000	0	0
INPP5D	0.011	0.021	-10000	0	-0.44	1	1
SOCS5	0.035	0.019	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.58	0.53	-10000	0	-1.2	155	155
SOCS1	-0.38	0.32	-10000	0	-0.78	90	90
SOCS3	-0.32	0.29	-10000	0	-0.77	60	60
FCER2	-0.84	0.66	-10000	0	-1.3	262	262
PARP14	0.004	0.015	-10000	0	-10000	0	0
CCL17	-0.55	0.51	-10000	0	-1.2	127	127
GRB2	0.012	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.21	0.2	-10000	0	-0.8	3	3
T cell proliferation	-0.56	0.52	-10000	0	-1.2	126	126
IL4R/JAK1	-0.55	0.51	-10000	0	-1.2	131	131
EGR2	-0.62	0.54	-10000	0	-1.3	143	143
JAK2	-0.02	0.047	-10000	0	-0.47	3	3
JAK3	0.007	0.036	-10000	0	-0.73	1	1
PIK3R1	0.012	0	-10000	0	-10000	0	0
JAK1	0.004	0.023	-10000	0	-0.43	1	1
COL1A2	-0.18	0.21	-10000	0	-0.78	29	29
CCL26	-0.59	0.53	-10000	0	-1.3	134	134
IL4R	-0.58	0.54	-10000	0	-1.3	131	131
PTPN6	0.025	0.011	-10000	0	-10000	0	0
IL13RA2	-0.58	0.51	-10000	0	-1.2	132	132
IL13RA1	-0.017	0.029	-10000	0	-10000	0	0
IRF4	-0.54	0.68	-10000	0	-1.5	151	151
ARG1	-0.13	0.14	-10000	0	-0.7	6	6
CBL	-0.37	0.33	-10000	0	-0.76	137	137
GTF3A	-0.016	0.14	-10000	0	-0.75	16	16
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.023	0.049	-10000	0	-0.34	2	2
IRF4/BCL6	-0.47	0.63	-10000	0	-1.4	151	151
CD40LG	-0.035	0.13	-10000	0	-0.45	37	37
MAPK14	-0.36	0.33	-10000	0	-0.78	122	122
mitosis	-0.27	0.26	-10000	0	-0.63	73	73
STAT6	-0.62	0.6	-10000	0	-1.4	136	136
SPI1	0.009	0.052	-10000	0	-0.44	6	6
RPS6KB1	-0.26	0.25	-10000	0	-0.62	59	59
STAT6 (dimer)	-0.62	0.6	-10000	0	-1.4	136	136
STAT6 (dimer)/PARP14	-0.63	0.56	-10000	0	-1.3	145	145
mast cell activation	0.014	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.28	0.26	-10000	0	-0.63	77	77
FRAP1	-0.28	0.27	-10000	0	-0.66	73	73
LTA	-0.55	0.51	-10000	0	-1.2	122	122
FES	0.01	0.03	-10000	0	-0.44	2	2
T-helper 1 cell differentiation	0.61	0.58	1.3	137	-10000	0	137
CCL11	-0.59	0.57	-10000	0	-1.3	137	137
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.27	0.25	-10000	0	-0.61	73	73
IL2RG	0.007	0.031	-10000	0	-0.43	2	2
IL10	-0.57	0.54	-10000	0	-1.3	130	130
IRS1	0.012	0	-10000	0	-10000	0	0
IRS2	0.012	0	-10000	0	-10000	0	0
IL4	-0.13	0.12	-10000	0	-10000	0	0
IL5	-0.55	0.51	-10000	0	-1.2	123	123
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.43	0.38	-10000	0	-0.91	115	115
COL1A1	-0.27	0.3	-10000	0	-0.81	76	76
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.56	0.52	-10000	0	-1.3	117	117
IL2R gamma/JAK3	0.007	0.037	-10000	0	-0.39	3	3
TFF3	-0.56	0.53	-10000	0	-1.3	126	126
ALOX15	-0.57	0.53	-10000	0	-1.3	124	124
MYBL1	0.009	0.049	-10000	0	-0.73	2	2
T-helper 2 cell differentiation	-0.46	0.4	-10000	0	-0.95	131	131
SHC1	0.012	0	-10000	0	-10000	0	0
CEBPB	0.015	0.007	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.25	0.24	-10000	0	-0.62	28	28
mol:PI-3-4-5-P3	-0.28	0.27	-10000	0	-0.66	73	73
PI3K	-0.3	0.28	-10000	0	-0.7	73	73
DOK2	0.001	0.072	-10000	0	-0.44	12	12
ETS1	0.025	0.024	-10000	0	-0.4	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.19	0.19	-10000	0	-0.75	3	3
ITGB3	-0.55	0.51	-10000	0	-1.2	120	120
PIGR	-0.72	0.67	-10000	0	-1.4	181	181
IGHE	0.046	0.037	0.25	1	-10000	0	1
MAPKKK cascade	-0.19	0.18	-10000	0	-0.73	3	3
BCL6	0.018	0.01	-10000	0	-10000	0	0
OPRM1	-0.55	0.5	-10000	0	-1.2	121	121
RETNLB	-0.77	0.68	-10000	0	-1.5	206	206
SELP	-0.61	0.6	-10000	0	-1.4	136	136
AICDA	-0.53	0.49	-10000	0	-1.2	122	122

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.41	0.33	-9999	-0.95	78	78
PCK1	-0.72	0.61	-9999	-1.4	206	206
HNF4A	-0.47	0.39	-9999	-1.1	93	93
KCNJ11	-0.41	0.34	-9999	-1	66	66
AKT1	-0.21	0.13	-9999	-10000	0	0
response to starvation	-0.015	0.025	-9999	-10000	0	0
DLK1	-0.43	0.36	-9999	-1	77	77
NKX2-1	-0.25	0.24	-9999	-0.76	51	51
ACADM	-0.41	0.34	-9999	-0.96	81	81
TAT	-0.69	0.59	-9999	-1.3	212	212
CEBPB	0.001	0.027	-9999	-10000	0	0
CEBPA	0	0.044	-9999	-0.44	3	3
TTR	-0.43	0.44	-9999	-1.1	125	125
PKLR	-0.48	0.4	-9999	-1	118	118
APOA1	-0.51	0.41	-9999	-1.2	88	88
CPT1C	-0.41	0.33	-9999	-0.97	75	75
ALAS1	-0.19	0.13	-9999	-10000	0	0
TFRC	-0.36	0.23	-9999	-0.73	60	60
FOXF1	0.02	0.077	-9999	-0.43	9	9
NF1	0.018	0	-9999	-10000	0	0
HNF1A (dimer)	-0.091	0.058	-9999	-0.5	2	2
CPT1A	-0.41	0.33	-9999	-0.96	76	76
HMGCS1	-0.41	0.33	-9999	-0.97	74	74
NR3C1	-0.082	0.13	-9999	-0.47	32	32
CPT1B	-0.41	0.33	-9999	-0.96	78	78
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	-0.079	0.04	-9999	-10000	0	0
GCK	-0.42	0.34	-9999	-0.98	80	80
CREB1	-0.052	0.073	-9999	-10000	0	0
IGFBP1	-0.32	0.27	-9999	-0.75	102	102
PDX1	-0.61	0.24	-9999	-0.81	187	187
UCP2	-0.41	0.33	-9999	-0.97	74	74
ALDOB	-0.46	0.38	-9999	-1	97	97
AFP	-0.13	0.21	-9999	-0.69	44	44
BDH1	-0.41	0.33	-9999	-0.96	78	78
HADH	-0.41	0.33	-9999	-0.95	76	76
F2	-0.56	0.44	-9999	-1.2	110	110
HNF1A	-0.091	0.058	-9999	-0.5	2	2
G6PC	-0.26	0.39	-9999	-1.3	57	57
SLC2A2	-0.33	0.2	-9999	-0.96	15	15
INS	0.009	0.04	-9999	-10000	0	0
FOXA1	-0.048	0.16	-9999	-0.4	56	56
FOXA3	-0.14	0.13	-9999	-0.41	39	39
FOXA2	-0.48	0.37	-9999	-1.1	79	79
ABCC8	-0.46	0.38	-9999	-1	108	108
ALB	-0.14	0.22	-9999	-0.64	62	62

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	0.003	0.078	-10000	0	-0.48	2	2
fibroblast growth factor receptor signaling pathway	0.003	0.077	-10000	0	-0.48	2	2
LAMA1	-0.11	0.2	-10000	0	-0.44	128	128
PRNP	0.011	0.021	-10000	0	-0.44	1	1
GPC1/SLIT2	-0.069	0.14	-10000	0	-0.3	124	124
SMAD2	0.025	0.031	-10000	0	-0.43	1	1
GPC1/PrPc/Cu2+	0.014	0.029	-10000	0	-0.33	3	3
GPC1/Laminin alpha1	-0.073	0.14	-10000	0	-0.3	130	130
TDGF1	-0.29	0.36	-10000	0	-0.72	188	188
CRIPTO/GPC1	-0.21	0.28	-10000	0	-0.54	189	189
APP/GPC1	0.016	0.03	-10000	0	-0.43	2	2
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.18	0.24	-10000	0	-0.47	181	181
FLT1	0.012	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.023	0.029	-10000	0	-0.47	1	1
SERPINC1	0	0.077	-10000	0	-0.73	5	5
FYN	-0.18	0.24	-10000	0	-0.47	181	181
FGR	-0.18	0.24	-10000	0	-0.48	182	182
positive regulation of MAPKKK cascade	-0.17	0.2	-10000	0	-0.38	187	187
SLIT2	-0.11	0.2	-10000	0	-0.44	122	122
GPC1/NRG	-0.026	0.11	-10000	0	-0.3	62	62
NRG1	-0.047	0.15	-10000	0	-0.44	60	60
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.022	0.035	-10000	0	-0.47	2	2
LYN	-0.18	0.24	-10000	0	-0.47	181	181
mol:Spermine	0.008	0.03	-10000	0	-0.43	2	2
cell growth	0.003	0.077	-10000	0	-0.48	2	2
BMP signaling pathway	-0.01	0.04	0.58	2	-10000	0	2
SRC	-0.18	0.24	-10000	0	-0.47	181	181
TGFBR1	0.011	0.021	-10000	0	-0.44	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.1	0.2	-10000	0	-0.46	111	111
GPC1	0.01	0.041	-10000	0	-0.58	2	2
TGFBR1 (dimer)	0.011	0.021	-10000	0	-0.44	1	1
VEGFA	0.011	0.035	-10000	0	-0.73	1	1
BLK	-0.27	0.27	-10000	0	-0.57	182	182
HCK	-0.18	0.25	-10000	0	-0.48	181	181
FGF2	-0.018	0.11	-10000	0	-0.44	31	31
FGFR1	0.008	0.042	-10000	0	-0.44	4	4
VEGFR1 homodimer	0.012	0	-10000	0	-10000	0	0
TGFBR2	0.012	0	-10000	0	-10000	0	0
cell death	0.016	0.03	-10000	0	-0.42	2	2
ATIII/GPC1	0.007	0.066	-10000	0	-0.52	7	7
PLA2G2A/GPC1	-0.065	0.15	-10000	0	-0.32	113	113
LCK	-0.19	0.24	-10000	0	-0.48	188	188
neuron differentiation	-0.026	0.11	-10000	0	-0.3	62	62
PrPc/Cu2+	0.008	0.015	-10000	0	-0.31	1	1
APP	0.012	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.012	0	-10000	0	-10000	0	0

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.05	0.12	-9999	-0.27	102	102
EFNA5	-0.079	0.18	-9999	-0.44	93	93
FYN	-0.038	0.11	-9999	-0.44	6	6
neuron projection morphogenesis	-0.05	0.12	-9999	-0.27	102	102
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.05	0.12	-9999	-0.27	102	102
EPHA5	-0.008	0.079	-9999	-0.44	15	15

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.16	0.22	-9999	-0.39	214	214
NF kappa B1 p50/RelA/I kappa B alpha	-0.13	0.2	-9999	-0.49	31	31
alphaV/beta3 Integrin/Osteopontin/Src	-0.24	0.28	-9999	-0.55	214	214
AP1	-0.13	0.21	-9999	-0.79	3	3
ILK	-0.18	0.23	-9999	-0.48	30	30
bone resorption	-0.13	0.2	-9999	-0.69	1	1
PTK2B	0.011	0.021	-9999	-0.44	1	1
PYK2/p130Cas	-0.15	0.21	-9999	-0.44	31	31
ITGAV	0.014	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.017	0.021	-9999	-0.3	2	2
alphaV/beta3 Integrin/Osteopontin	-0.2	0.25	-9999	-0.47	214	214
MAP3K1	-0.18	0.23	-9999	-0.42	214	214
JUN	0.013	0.001	-9999	-10000	0	0
MAPK3	-0.17	0.22	-9999	-0.54	31	31
MAPK1	-0.16	0.22	-9999	-0.53	30	30
Rac1/GDP	0.009	0	-9999	-10000	0	0
NFKB1	0.012	0	-9999	-10000	0	0
MAPK8	-0.16	0.22	-9999	-0.39	214	214
ITGB3	0.01	0.046	-9999	-0.43	5	5
NFKBIA	-0.15	0.22	-9999	-0.54	31	31
FOS	0.006	0.055	-9999	-0.44	7	7
CD44	0.012	0	-9999	-10000	0	0
CHUK	0.012	0	-9999	-10000	0	0
PLAU	-0.15	0.25	-9999	-0.8	30	30
NF kappa B1 p50/RelA	-0.16	0.18	-9999	-0.53	31	31
BCAR1	0.011	0.021	-9999	-0.44	1	1
RELA	0.012	0	-9999	-10000	0	0
alphaV beta3 Integrin	0.019	0.033	-9999	-0.31	1	1
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.18	0.23	-9999	-0.42	214	214
VAV3	-0.18	0.24	-9999	-0.53	59	59
MAP3K14	-0.18	0.23	-9999	-0.42	214	214
ROCK2	0.01	0.03	-9999	-0.44	2	2
SPP1	-0.34	0.37	-9999	-0.72	218	218
RAC1	0.012	0	-9999	-10000	0	0
Rac1/GTP	-0.16	0.22	-9999	-0.49	59	59
MMP2	-0.11	0.19	-9999	-0.79	4	4

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.4	0.44	-10000	0	-1.1	92	92
IL23A	-0.48	0.5	-10000	0	-1.2	97	97
NF kappa B1 p50/RelA/I kappa B alpha	-0.46	0.42	-10000	0	-1.1	108	108
positive regulation of T cell mediated cytotoxicity	-0.44	0.49	-10000	0	-1.2	88	88
ITGA3	-0.41	0.44	-10000	0	-1.1	83	83
IL17F	-0.31	0.33	-10000	0	-0.77	103	103
IL12B	-0.016	0.076	-10000	0	-0.77	4	4
STAT1 (dimer)	-0.42	0.47	-10000	0	-1.2	87	87
CD4	-0.4	0.45	-10000	0	-1.1	92	92
IL23	-0.47	0.47	-10000	0	-1.2	98	98
IL23R	-0.083	0.22	-10000	0	-1.4	11	11
IL1B	-0.46	0.49	-10000	0	-1.3	81	81
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.5	0.48	-10000	0	-1.1	134	134
TYK2	-0.004	0.019	-10000	0	-10000	0	0
STAT4	-0.011	0.1	-10000	0	-0.44	24	24
STAT3	0.012	0.002	-10000	0	-10000	0	0
IL18RAP	-0.012	0.1	-10000	0	-0.45	24	24
IL12RB1	-0.024	0.098	-10000	0	-0.48	19	19
PIK3CA	0.012	0.002	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.018	0.073	-10000	0	-0.35	18	18
IL23R/JAK2	-0.09	0.22	-10000	0	-1.3	11	11
positive regulation of chronic inflammatory response	-0.44	0.49	-10000	0	-1.2	88	88
natural killer cell activation	0.006	0.013	0.077	11	-10000	0	11
JAK2	-0.006	0.046	-10000	0	-0.46	3	3
PIK3R1	0.012	0.002	-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	-0.44	0.44	-10000	0	-1.1	98	98
ALOX12B	-0.4	0.43	-10000	0	-1.1	82	82
CXCL1	-0.5	0.48	-10000	0	-1.1	126	126
T cell proliferation	-0.44	0.49	-10000	0	-1.2	88	88
NFKBIA	0.009	0.003	-10000	0	-10000	0	0
IL17A	-0.28	0.29	-10000	0	-0.66	107	107
PI3K	-0.44	0.42	-10000	0	-1.1	103	103
IFNG	-0.017	0.038	0.15	7	-0.097	43	50
STAT3 (dimer)	-0.45	0.42	-10000	0	-1.1	106	106
IL18R1	0.003	0.062	-10000	0	-0.43	9	9
IL23/IL23R/JAK2/TYK2/SOCS3	-0.23	0.25	-10000	0	-0.68	44	44
IL18/IL18R	0.006	0.076	-10000	0	-0.46	1	1
macrophage activation	-0.026	0.017	-10000	0	-0.045	65	65
TNF	-0.44	0.46	-10000	0	-1.2	88	88
STAT3/STAT4	-0.44	0.42	-10000	0	-1.1	101	101
STAT4 (dimer)	-0.43	0.48	-10000	0	-1.2	89	89
IL18	0.01	0.03	-10000	0	-0.44	2	2
IL19	-0.39	0.43	-10000	0	-1.1	86	86
STAT5A (dimer)	-0.42	0.47	-10000	0	-1.2	85	85
STAT1	0.011	0.035	-10000	0	-0.73	1	1
SOCS3	0.011	0.035	-10000	0	-0.73	1	1
CXCL9	-0.43	0.46	-10000	0	-1.1	96	96
MPO	-0.4	0.43	-10000	0	-1.1	81	81
positive regulation of humoral immune response	-0.44	0.49	-10000	0	-1.2	88	88
IL23/IL23R/JAK2/TYK2	-0.46	0.52	-10000	0	-1.3	88	88
IL6	-0.45	0.48	-10000	0	-1.2	102	102
STAT5A	0.012	0	-10000	0	-10000	0	0
IL2	0.007	0.01	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.006	0.013	0.077	11	-10000	0	11
CD3E	-0.41	0.45	-10000	0	-1.1	83	83
keratinocyte proliferation	-0.44	0.49	-10000	0	-1.2	88	88
NOS2	-0.42	0.46	-10000	0	-1.1	98	98

×

BCR signaling pathway

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
JUN	-0.099	0.2	-9999	-0.49	76	76
IKBKB	-0.043	0.098	-9999	-0.26	44	44
AKT1	-0.071	0.12	-9999	-0.27	78	78
IKBKG	-0.045	0.11	-9999	-0.28	50	50
CALM1	-0.12	0.23	-9999	-0.55	87	87
PIK3CA	0.012	0.001	-9999	-10000	0	0
MAP3K1	-0.16	0.29	-9999	-0.7	83	83
MAP3K7	0.012	0	-9999	-10000	0	0
mol:Ca2+	-0.14	0.24	-9999	-0.58	89	89
DOK1	0.012	0	-9999	-10000	0	0
AP-1	-0.049	0.12	-9999	-0.27	70	70
LYN	0.012	0	-9999	-10000	0	0
BLNK	0.005	0.055	-9999	-0.44	7	7
SHC1	0.012	0	-9999	-10000	0	0
BCR complex	-0.14	0.22	-9999	-0.4	173	173
CD22	-0.24	0.35	-9999	-0.75	120	120
CAMK2G	-0.11	0.21	-9999	-0.55	71	71
CSNK2A1	0.012	0	-9999	-10000	0	0
INPP5D	0.011	0.021	-9999	-0.44	1	1
SHC/GRB2/SOS1	-0.09	0.13	-9999	-0.54	3	3
GO:0007205	-0.14	0.25	-9999	-0.6	89	89
SYK	0.012	0	-9999	-10000	0	0
ELK1	-0.12	0.24	-9999	-0.56	86	86
NFATC1	-0.15	0.26	-9999	-0.52	122	122
B-cell antigen/BCR complex	-0.14	0.22	-9999	-0.4	173	173
PAG1/CSK	0.013	0.042	-9999	-0.3	8	8
NFKBIB	-0.005	0.034	-9999	-10000	0	0
HRAS	-0.11	0.2	-9999	-0.51	77	77
NFKBIA	-0.005	0.033	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.002	0.027	-9999	-10000	0	0
RasGAP/Csk	-0.11	0.2	-9999	-0.5	77	77
mol:GDP	-0.13	0.24	-9999	-0.57	87	87
PTEN	0.01	0.03	-9999	-0.44	2	2
CD79B	-0.053	0.16	-9999	-0.44	67	67
NF-kappa-B/RelA/I kappa B alpha	0.002	0.027	-9999	-10000	0	0
GRB2	0.012	0	-9999	-10000	0	0
PI3K/BCAP/CD19	-0.18	0.28	-9999	-0.58	127	127
PIK3R1	0.012	0	-9999	-10000	0	0
mol:IP3	-0.14	0.26	-9999	-0.6	89	89
CSK	0.012	0	-9999	-10000	0	0
FOS	-0.11	0.22	-9999	-0.56	74	74
CHUK	-0.045	0.1	-9999	-0.27	50	50
IBTK	0.011	0.021	-9999	-0.44	1	1
CARD11/BCL10/MALT1/TAK1	-0.12	0.2	-9999	-0.52	78	78
PTPN6	-0.2	0.34	-9999	-0.7	120	120
RELA	0.012	0	-9999	-10000	0	0
BCL2A1	0.003	0.027	-9999	-0.12	10	10
VAV2	-0.21	0.35	-9999	-0.72	124	124
ubiquitin-dependent protein catabolic process	-0.001	0.033	-9999	-10000	0	0
BTK	-0.14	0.37	-9999	-1.1	60	60
CD19	-0.24	0.34	-9999	-0.74	121	121
MAP4K1	-0.034	0.14	-9999	-0.44	47	47
CD72	0.011	0.021	-9999	-0.44	1	1
PAG1	0.004	0.059	-9999	-0.44	8	8
MAPK14	-0.12	0.24	-9999	-0.57	82	82
SH3BP5	0.009	0.036	-9999	-0.44	3	3
PIK3AP1	-0.13	0.25	-9999	-0.63	77	77
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.17	0.29	-9999	-0.7	85	85
RAF1	-0.095	0.19	-9999	-0.49	71	71
RasGAP/p62DOK/SHIP	-0.099	0.2	-9999	-0.48	77	77
CD79A	-0.15	0.22	-9999	-0.44	170	170
re-entry into mitotic cell cycle	-0.05	0.12	-9999	-0.28	70	70
RASA1	0.012	0.001	-9999	-10000	0	0
MAPK3	-0.069	0.16	-9999	-0.45	49	49
MAPK1	-0.068	0.16	-9999	-0.45	49	49
CD72/SHP1	-0.18	0.31	-9999	-0.64	119	119
NFKB1	0.012	0	-9999	-10000	0	0
MAPK8	-0.12	0.24	-9999	-0.57	82	82
actin cytoskeleton organization	-0.17	0.28	-9999	-0.58	124	124
NF-kappa-B/RelA	0.008	0.054	-9999	-0.27	1	1
Calcineurin	-0.09	0.19	-9999	-0.55	53	53
PI3K	-0.19	0.24	-9999	-0.58	103	103
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.14	0.26	-9999	-0.62	89	89
SOS1	0.012	0	-9999	-10000	0	0
Bam32/HPK1	-0.18	0.35	-9999	-0.87	84	84
DAPP1	-0.22	0.38	-9999	-1	78	78
cytokine secretion	-0.14	0.23	-9999	-0.48	122	122
mol:DAG	-0.14	0.26	-9999	-0.6	89	89
PLCG2	-0.032	0.13	-9999	-0.44	45	45
MAP2K1	-0.082	0.18	-9999	-0.45	69	69
B-cell antigen/BCR complex/FcgammaRIIB	-0.14	0.23	-9999	-0.58	77	77
mol:PI-3-4-5-P3	-0.13	0.16	-9999	-0.38	103	103
ETS1	-0.093	0.19	-9999	-0.55	53	53
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.085	0.17	-9999	-0.42	66	66
B-cell antigen/BCR complex/LYN	-0.19	0.31	-9999	-0.79	84	84
MALT1	0.011	0.021	-9999	-0.44	1	1
TRAF6	0.012	0	-9999	-10000	0	0
RAC1	-0.19	0.31	-9999	-0.64	124	124
B-cell antigen/BCR complex/LYN/SYK	-0.21	0.3	-9999	-0.67	118	118
CARD11	-0.14	0.26	-9999	-0.58	96	96
FCGR2B	-0.041	0.14	-9999	-0.44	54	54
PPP3CA	0.012	0	-9999	-10000	0	0
BCL10	0.011	0.021	-9999	-0.44	1	1
IKK complex	-0.011	0.043	-9999	-0.1	1	1
PTPRC	-0.024	0.12	-9999	-0.44	37	37
PDPK1	-0.069	0.12	-9999	-0.27	70	70
PPP3CB	0.012	0	-9999	-10000	0	0
PPP3CC	0.012	0	-9999	-10000	0	0
POU2F2	0.003	0.026	-9999	-0.093	13	13

×

Syndecan-4-mediated signaling events

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
PTK2	-0.024	0.1	-9999	-0.39	29	29
Syndecan-4/Syndesmos	-0.14	0.21	-9999	-0.52	71	71
positive regulation of JNK cascade	-0.16	0.2	-9999	-0.48	91	91
Syndecan-4/ADAM12	-0.38	0.27	-9999	-0.67	157	157
CCL5	-0.007	0.092	-9999	-0.44	20	20
Rac1/GDP	0.009	0	-9999	-10000	0	0
DNM2	0.012	0	-9999	-10000	0	0
ITGA5	0.007	0.06	-9999	-0.73	3	3
SDCBP	0.01	0.03	-9999	-0.44	2	2
PLG	-0.13	0.29	-9999	-0.74	86	86
ADAM12	-0.43	0.36	-9999	-0.73	274	274
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.012	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.064	0.068	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.2	0.22	-9999	-0.53	109	109
Syndecan-4/CXCL12/CXCR4	-0.17	0.21	-9999	-0.5	91	91
Syndecan-4/Laminin alpha3	-0.15	0.21	-9999	-0.52	74	74
MDK	0.006	0.069	-9999	-0.73	4	4
Syndecan-4/FZD7	-0.14	0.21	-9999	-0.52	71	71
Syndecan-4/Midkine	-0.15	0.21	-9999	-0.52	73	73
FZD7	0.012	0	-9999	-10000	0	0
Syndecan-4/FGFR1/FGF	-0.16	0.19	-9999	-0.5	79	79
THBS1	0.011	0.035	-9999	-0.73	1	1
integrin-mediated signaling pathway	-0.15	0.21	-9999	-0.51	76	76
positive regulation of MAPKKK cascade	-0.16	0.2	-9999	-0.48	91	91
Syndecan-4/TACI	-0.23	0.22	-9999	-0.51	138	138
CXCR4	0.012	0	-9999	-10000	0	0
cell adhesion	0.011	0.073	-9999	-0.28	19	19
Syndecan-4/Dynamin	-0.14	0.21	-9999	-0.52	71	71
Syndecan-4/TSP1	-0.14	0.21	-9999	-0.52	71	71
Syndecan-4/GIPC	-0.14	0.21	-9999	-0.52	71	71
Syndecan-4/RANTES	-0.15	0.21	-9999	-0.52	80	80
ITGB1	0.012	0	-9999	-10000	0	0
LAMA1	-0.11	0.2	-9999	-0.44	128	128
LAMA3	0.007	0.054	-9999	-0.5	5	5
RAC1	0.012	0	-9999	-10000	0	0
PRKCA	0.045	0.048	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	-0.14	0.21	-9999	-0.52	71	71
TFPI	0.009	0.036	-9999	-0.44	3	3
F2	-0.23	0.34	-9999	-0.73	147	147
alpha5/beta1 Integrin	0.015	0.046	-9999	-0.55	3	3
positive regulation of cell adhesion	-0.19	0.22	-9999	-0.51	106	106
ACTN1	0.012	0	-9999	-10000	0	0
TNC	-0.004	0.1	-9999	-0.61	12	12
Syndecan-4/CXCL12	-0.18	0.22	-9999	-0.51	98	98
FGF6	-0.003	0.048	-9999	-0.73	2	2
RHOA	0.012	0	-9999	-10000	0	0
CXCL12	-0.067	0.17	-9999	-0.44	81	81
TNFRSF13B	-0.18	0.22	-9999	-0.44	193	193
FGF2	-0.018	0.11	-9999	-0.44	31	31
FGFR1	0.008	0.042	-9999	-0.44	4	4
Syndecan-4/PI-4-5-P2	-0.15	0.21	-9999	-0.52	71	71
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.026	0.16	-9999	-0.64	29	29
cell migration	-0.024	0.025	-9999	-10000	0	0
PRKCD	0.016	0.01	-9999	-10000	0	0
vasculogenesis	-0.14	0.2	-9999	-0.5	71	71
SDC4	-0.16	0.22	-9999	-0.55	71	71
Syndecan-4/Tenascin C	-0.15	0.22	-9999	-0.53	76	76
Syndecan-4/PI-4-5-P2/PKC alpha	-0.051	0.054	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.14	0.21	-9999	-0.52	72	72
MMP9	-0.053	0.21	-9999	-0.71	40	40
Rac1/GTP	0.007	0.074	-9999	-0.29	19	19
cytoskeleton organization	-0.14	0.2	-9999	-0.5	71	71
GIPC1	0.011	0.021	-9999	-0.44	1	1
Syndecan-4/TFPI	-0.14	0.21	-9999	-0.52	71	71

×

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

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
MAP4K1	-0.056	0.18	-10000	0	-0.42	81	81
CRKL	-0.044	0.17	-10000	0	-0.42	78	78
HRAS	-0.034	0.17	-10000	0	-0.47	24	24
mol:PIP3	-0.052	0.16	-10000	0	-0.4	78	78
SPRED1	0.012	0	-10000	0	-10000	0	0
SPRED2	0.012	0	-10000	0	-10000	0	0
GAB1	-0.053	0.18	-10000	0	-0.44	78	78
FOXO3	-0.035	0.16	-10000	0	-0.38	78	78
AKT1	-0.044	0.17	-10000	0	-0.41	78	78
BAD	-0.035	0.16	-10000	0	-0.38	78	78
megakaryocyte differentiation	-0.088	0.22	-10000	0	-0.46	108	108
GSK3B	-0.035	0.16	-10000	0	-0.38	78	78
RAF1	-0.019	0.14	-10000	0	-0.38	24	24
SHC1	0.012	0	-10000	0	-10000	0	0
STAT3	-0.053	0.18	-10000	0	-0.44	78	78
STAT1	-0.14	0.42	-10000	0	-1	78	78
HRAS/SPRED1	-0.02	0.14	-10000	0	-0.38	24	24
cell proliferation	-0.051	0.18	-10000	0	-0.43	78	78
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
TEC	0.011	0.035	-10000	0	-0.73	1	1
RPS6KB1	-0.052	0.18	-10000	0	-0.44	78	78
HRAS/SPRED2	-0.02	0.14	-10000	0	-0.38	24	24
LYN/TEC/p62DOK	-0.038	0.17	-10000	0	-0.41	79	79
MAPK3	-0.002	0.11	-10000	0	-0.29	9	9
STAP1	-0.1	0.21	-10000	0	-0.51	79	79
GRAP2	-0.006	0.089	-10000	0	-0.44	19	19
JAK2	-0.12	0.36	-10000	0	-0.87	78	78
STAT1 (dimer)	-0.14	0.41	-10000	0	-1	78	78
mol:Gleevec	0.001	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.056	0.2	-10000	0	-0.46	79	79
actin filament polymerization	-0.055	0.18	-10000	0	-0.44	81	81
LYN	0.012	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.12	0.27	-10000	0	-0.67	79	79
PIK3R1	0.012	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.028	0.16	-10000	0	-0.37	78	78
PI3K	-0.038	0.18	-10000	0	-0.42	78	78
PTEN	0.01	0.03	-10000	0	-0.44	2	2
SCF/KIT/EPO/EPOR	-0.17	0.48	-10000	0	-1.2	78	78
MAPK8	-0.053	0.18	-10000	0	-0.44	78	78
STAT3 (dimer)	-0.051	0.18	-10000	0	-0.43	78	78
positive regulation of transcription	0.002	0.091	-10000	0	-0.25	3	3
mol:GDP	-0.041	0.18	-10000	0	-0.52	24	24
PIK3C2B	-0.053	0.18	-10000	0	-0.44	78	78
CBL/CRKL	-0.035	0.17	-10000	0	-0.39	78	78
FER	-0.053	0.18	-10000	0	-0.44	78	78
SH2B3	-0.053	0.18	-10000	0	-0.44	78	78
PDPK1	-0.042	0.15	-10000	0	-0.36	78	78
SNAI2	-0.054	0.18	-10000	0	-0.44	78	78
positive regulation of cell proliferation	-0.095	0.31	-10000	0	-0.75	78	78
KITLG	0	0.073	-10000	0	-0.46	11	11
cell motility	-0.095	0.31	-10000	0	-0.75	78	78
PTPN6	0.014	0.01	-10000	0	-10000	0	0
EPOR	-0.015	0.14	-10000	0	-0.8	1	1
STAT5A (dimer)	-0.075	0.26	-10000	0	-0.62	78	78
SOCS1	-0.006	0.11	-10000	0	-0.73	11	11
cell migration	0.075	0.2	0.48	78	-10000	0	78
SOS1	0.012	0	-10000	0	-10000	0	0
EPO	0	0.069	-10000	0	-0.73	4	4
VAV1	-0.009	0.096	-10000	0	-0.44	22	22
GRB10	-0.053	0.18	-10000	0	-0.44	78	78
PTPN11	0.013	0.007	-10000	0	-10000	0	0
SCF/KIT	-0.062	0.19	-10000	0	-0.47	78	78
GO:0007205	0.002	0.01	-10000	0	-10000	0	0
MAP2K1	-0.006	0.12	-10000	0	-0.32	9	9
CBL	0.012	0	-10000	0	-10000	0	0
KIT	-0.18	0.49	-10000	0	-1.3	78	78
MAP2K2	-0.007	0.12	-10000	0	-0.32	10	10
SHC/Grb2/SOS1	-0.037	0.17	-10000	0	-0.41	78	78
STAT5A	-0.078	0.26	-10000	0	-0.64	78	78
GRB2	0.012	0	-10000	0	-10000	0	0
response to radiation	-0.052	0.18	-10000	0	-0.44	78	78
SHC/GRAP2	0.005	0.064	-10000	0	-0.3	19	19
PTPRO	-0.091	0.22	-10000	0	-0.46	108	108
SH2B2	-0.056	0.19	-10000	0	-0.45	81	81
DOK1	0.012	0	-10000	0	-10000	0	0
MATK	-0.077	0.2	-10000	0	-0.49	78	78
CREBBP	0.013	0.047	-10000	0	-10000	0	0
BCL2	-0.062	0.31	-10000	0	-1.4	22	22

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.006	0.22	-10000	0	-0.52	39	39
PTK2B	0.012	0.021	-10000	0	-0.44	1	1
mol:Ca2+	0.009	0.25	-10000	0	-0.97	24	24
EDN1	0.045	0.14	-10000	0	-0.51	2	2
EDN3	-0.21	0.22	-10000	0	-0.44	226	226
EDN2	-0.12	0.21	-10000	0	-0.44	138	138
HRAS/GDP	0.012	0.15	-10000	0	-0.46	10	10
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.04	0.11	-10000	0	-0.45	3	3
ADCY4	-0.026	0.18	-10000	0	-0.43	49	49
ADCY5	-0.095	0.21	-10000	0	-0.52	54	54
ADCY6	-0.026	0.18	-10000	0	-0.44	43	43
ADCY7	-0.026	0.18	-10000	0	-0.44	43	43
ADCY1	-0.035	0.18	-10000	0	-0.44	50	50
ADCY2	-0.042	0.19	-10000	0	-0.54	33	33
ADCY3	-0.026	0.18	-10000	0	-0.44	43	43
ADCY8	-0.038	0.18	-10000	0	-0.44	45	45
ADCY9	-0.026	0.17	-10000	0	-0.43	46	46
arachidonic acid secretion	-0.004	0.16	-10000	0	-0.49	22	22
ETB receptor/Endothelin-1/Gq/GTP	0.026	0.089	-10000	0	-0.36	10	10
GNAO1	-0.11	0.2	-10000	0	-0.44	125	125
HRAS	0.011	0.021	-10000	0	-0.44	1	1
ETA receptor/Endothelin-1/G12/GTP	0.088	0.26	0.31	219	-0.48	39	258
ETA receptor/Endothelin-1/Gs/GTP	0.063	0.26	0.29	212	-0.46	49	261
mol:GTP	0.001	0.004	-10000	0	-10000	0	0
COL3A1	-0.002	0.24	-10000	0	-0.59	45	45
EDNRB	-0.005	0.085	-10000	0	-0.43	16	16
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.018	0.26	-10000	0	-0.62	54	54
CYSLTR1	-0.047	0.3	-10000	0	-0.6	88	88
SLC9A1	0.017	0.12	-10000	0	-0.27	26	26
mol:GDP	0.006	0.16	-10000	0	-0.48	12	12
SLC9A3	-0.24	0.34	-10000	0	-0.63	142	142
RAF1	0	0.13	-10000	0	-0.52	7	7
JUN	0.038	0.15	-10000	0	-0.68	4	4
JAK2	0.004	0.22	-10000	0	-0.52	40	40
mol:IP3	0.033	0.11	-10000	0	-0.77	2	2
ETA receptor/Endothelin-1	0.08	0.32	0.36	222	-0.58	45	267
PLCB1	0.008	0.06	-10000	0	-0.73	3	3
PLCB2	0.013	0.002	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.15	0.24	-10000	0	-0.46	98	98
FOS	0.011	0.15	-10000	0	-0.88	8	8
Gai/GDP	-0.16	0.32	-10000	0	-0.67	125	125
CRK	0.013	0.001	-10000	0	-10000	0	0
mol:Ca ++	0.011	0.2	-10000	0	-0.56	24	24
BCAR1	0.011	0.021	-10000	0	-0.44	1	1
PRKCB1	0.031	0.1	-10000	0	-0.73	2	2
GNAQ	0.012	0.03	-10000	0	-0.44	2	2
GNAZ	0.007	0.047	-10000	0	-0.44	5	5
GNAL	-0.014	0.11	-10000	0	-0.44	27	27
Gs family/GDP	-0.05	0.12	-10000	0	-0.46	18	18
ETA receptor/Endothelin-1/Gq/GTP	0.037	0.13	-10000	0	-0.39	12	12
MAPK14	0.035	0.078	-10000	0	-0.65	2	2
TRPC6	0.005	0.27	-10000	0	-1.1	24	24
GNAI2	0.012	0	-10000	0	-10000	0	0
GNAI3	0.012	0	-10000	0	-10000	0	0
GNAI1	-0.001	0.077	-10000	0	-0.44	14	14
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.031	0.082	-10000	0	-0.55	3	3
ETB receptor/Endothelin-2	-0.09	0.16	-10000	0	-0.31	150	150
ETB receptor/Endothelin-3	-0.15	0.17	-10000	0	-0.31	232	232
ETB receptor/Endothelin-1	0.033	0.13	-10000	0	-0.41	13	13
MAPK3	0.009	0.15	-10000	0	-0.74	9	9
MAPK1	0.009	0.15	-10000	0	-0.74	9	9
Rac1/GDP	0.012	0.15	-10000	0	-0.49	8	8
cAMP biosynthetic process	-0.071	0.18	-10000	0	-0.47	49	49
MAPK8	0.03	0.17	-10000	0	-0.61	17	17
SRC	0.012	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.034	0.15	-10000	0	-0.46	26	26
p130Cas/CRK/Src/PYK2	-0.021	0.18	-10000	0	-0.58	22	22
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	0.012	0.15	-10000	0	-0.46	10	10
COL1A2	0.002	0.25	-10000	0	-0.64	39	39
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.09	0.23	-10000	0	-0.5	63	63
mol:DAG	0.033	0.11	-10000	0	-0.77	2	2
MAP2K2	0.007	0.14	-10000	0	-0.58	9	9
MAP2K1	0.007	0.14	-10000	0	-0.58	9	9
EDNRA	0.004	0.23	-10000	0	-0.75	26	26
positive regulation of muscle contraction	0.012	0.19	-10000	0	-0.45	37	37
Gq family/GDP	-0.048	0.11	-10000	0	-0.49	8	8
HRAS/GTP	-0.009	0.13	-10000	0	-0.46	9	9
PRKCH	0.036	0.1	-10000	0	-0.6	3	3
RAC1	0.012	0	-10000	0	-10000	0	0
PRKCA	0.036	0.1	-10000	0	-0.73	2	2
PRKCB	-0.012	0.16	-10000	0	-0.4	25	25
PRKCE	0.038	0.1	-10000	0	-0.72	2	2
PRKCD	0.037	0.1	-10000	0	-0.73	2	2
PRKCG	-0.1	0.22	-10000	0	-0.45	73	73
regulation of vascular smooth muscle contraction	0.008	0.18	-10000	0	-1	8	8
PRKCQ	0.035	0.11	-10000	0	-0.72	2	2
PLA2G4A	-0.007	0.18	-10000	0	-0.53	22	22
GNA14	0.012	0.03	-10000	0	-0.44	2	2
GNA15	0.005	0.077	-10000	0	-0.73	5	5
GNA12	0.012	0	-10000	0	-10000	0	0
GNA11	0.011	0.03	-10000	0	-0.44	2	2
Rac1/GTP	0.088	0.26	0.31	218	-0.48	39	257
MMP1	-0.37	0.32	-10000	0	-0.6	296	296

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.007	0.047	-9999	-0.44	5	5
LAT2	-0.091	0.17	-9999	-0.41	71	71
AP1	-0.15	0.21	-9999	-0.51	93	93
mol:PIP3	-0.12	0.21	-9999	-0.5	78	78
IKBKB	-0.072	0.14	-9999	-0.32	68	68
AKT1	-0.056	0.14	-9999	-0.46	5	5
IKBKG	-0.072	0.14	-9999	-0.32	69	69
MS4A2	-0.12	0.2	-9999	-0.44	135	135
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.012	0.001	-9999	-10000	0	0
MAP3K1	-0.087	0.19	-9999	-0.52	39	39
mol:Ca2+	-0.084	0.16	-9999	-0.36	78	78
LYN	0.011	0.004	-9999	-10000	0	0
CBLB	-0.09	0.16	-9999	-0.4	71	71
SHC1	0.012	0	-9999	-10000	0	0
RasGAP/p62DOK	0.023	0.016	-9999	-10000	0	0
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.011	0.021	-9999	-0.44	1	1
PLD2	-0.089	0.16	-9999	-0.39	70	70
PTPN13	-0.1	0.19	-9999	-0.45	72	72
PTPN11	0.008	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.048	0.14	-9999	-0.37	10	10
SYK	0.011	0.004	-9999	-10000	0	0
GRB2	0.012	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.15	0.2	-9999	-0.52	78	78
LAT	-0.092	0.17	-9999	-0.41	71	71
PAK2	-0.1	0.21	-9999	-0.46	87	87
NFATC2	-0.059	0.12	-9999	-0.63	14	14
HRAS	-0.12	0.23	-9999	-0.5	94	94
GAB2	0.012	0	-9999	-10000	0	0
PLA2G1B	0.033	0.023	-9999	-10000	0	0
Fc epsilon R1	-0.13	0.19	-9999	-0.49	70	70
Antigen/IgE/Fc epsilon R1	-0.12	0.18	-9999	-0.45	70	70
mol:GDP	-0.14	0.25	-9999	-0.56	94	94
JUN	0.012	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.012	0.001	-9999	-10000	0	0
FOS	0.005	0.055	-9999	-0.44	7	7
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.1	0.17	-9999	-0.43	71	71
CHUK	-0.072	0.14	-9999	-0.32	69	69
KLRG1	-0.083	0.15	-9999	-0.37	71	71
VAV1	-0.099	0.18	-9999	-0.42	80	80
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.09	0.16	-9999	-0.4	71	71
negative regulation of mast cell degranulation	-0.072	0.14	-9999	-0.36	53	53
BTK	-0.16	0.28	-9999	-0.61	102	102
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.14	0.24	-9999	-0.58	90	90
GAB2/PI3K/SHP2	-0.092	0.12	-9999	-0.51	5	5
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.099	0.18	-9999	-0.45	70	70
RAF1	0.026	0.025	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.12	0.21	-9999	-0.48	90	90
FCER1G	0.012	0.049	-9999	-0.45	5	5
FCER1A	-0.12	0.21	-9999	-0.45	133	133
Antigen/IgE/Fc epsilon R1/Fyn	-0.1	0.16	-9999	-0.41	70	70
MAPK3	0.032	0.023	-9999	-10000	0	0
MAPK1	0.032	0.023	-9999	-10000	0	0
NFKB1	0.012	0	-9999	-10000	0	0
MAPK8	-0.021	0.078	-9999	-0.48	4	4
DUSP1	0.01	0.03	-9999	-0.44	2	2
NF-kappa-B/RelA	-0.057	0.07	-9999	-0.23	1	1
actin cytoskeleton reorganization	-0.1	0.18	-9999	-0.44	71	71
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.12	0.18	-9999	-0.55	39	39
FER	-0.09	0.16	-9999	-0.4	72	72
RELA	0.012	0	-9999	-10000	0	0
ITK	-0.035	0.098	-9999	-0.45	19	19
SOS1	0.012	0	-9999	-10000	0	0
PLCG1	-0.13	0.25	-9999	-0.55	94	94
cytokine secretion	-0.041	0.05	-9999	-10000	0	0
SPHK1	-0.12	0.19	-9999	-0.42	99	99
PTK2	-0.1	0.19	-9999	-0.46	71	71
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.15	0.2	-9999	-0.53	78	78
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.11	0.21	-9999	-0.48	82	82
MAP2K2	0.029	0.025	-9999	-10000	0	0
MAP2K1	0.029	0.022	-9999	-10000	0	0
MAP2K7	0.011	0.021	-9999	-0.44	1	1
KLRG1/SHP2	-0.071	0.14	-9999	-0.45	14	14
MAP2K4	0.004	0.088	-9999	-0.93	4	4
Fc epsilon R1/FcgammaRIIB	-0.14	0.22	-9999	-0.51	90	90
mol:Choline	-0.088	0.15	-9999	-0.38	70	70
SHC/Grb2/SOS1	-0.074	0.16	-9999	-0.55	9	9
FYN	0.012	0	-9999	-10000	0	0
DOK1	0.012	0	-9999	-10000	0	0
PXN	-0.092	0.18	-9999	-0.42	71	71
HCLS1	-0.093	0.17	-9999	-0.42	71	71
PRKCB	-0.11	0.2	-9999	-0.42	106	106
FCGR2B	-0.041	0.14	-9999	-0.44	54	54
IGHE	-0.002	0.005	-9999	-10000	0	0
KLRG1/SHIP	-0.073	0.15	-9999	-0.48	14	14
LCP2	0.008	0.042	-9999	-0.44	4	4
PLA2G4A	-0.11	0.19	-9999	-0.43	100	100
RASA1	0.012	0.001	-9999	-10000	0	0
mol:Phosphatidic acid	-0.088	0.15	-9999	-0.38	70	70
IKK complex	-0.043	0.11	-9999	-0.25	37	37
WIPF1	0.009	0.036	-9999	-0.44	3	3

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.021	0.077	-10000	0	-10000	0	0
SMARCC2	0.011	0.013	-10000	0	-10000	0	0
SMARCC1	0.011	0.014	-10000	0	-10000	0	0
TBX21	-0.13	0.21	-10000	0	-0.66	44	44
SUMO2	0.012	0.007	-10000	0	-10000	0	0
STAT1 (dimer)	0.018	0.034	-10000	0	-0.72	1	1
FKBP4	0.011	0.035	-10000	0	-0.73	1	1
FKBP5	0.011	0.021	-10000	0	-0.44	1	1
GR alpha/HSP90/FKBP51/HSP90	0.11	0.11	0.33	16	-0.39	2	18
PRL	-0.085	0.14	-10000	0	-0.68	13	13
cortisol/GR alpha (dimer)/TIF2	0.26	0.22	0.55	100	-0.55	1	101
RELA	-0.061	0.081	-10000	0	-0.26	3	3
FGG	0.14	0.26	0.49	43	-0.56	28	71
GR beta/TIF2	0.11	0.13	0.35	24	-0.36	8	32
IFNG	-0.35	0.28	-10000	0	-0.8	90	90
apoptosis	0.013	0.16	0.48	14	-0.57	5	19
CREB1	0.009	0.036	-10000	0	-10000	0	0
histone acetylation	-0.069	0.13	0.41	3	-0.39	22	25
BGLAP	-0.079	0.12	-10000	0	-0.49	9	9
GR/PKAc	0.068	0.14	0.33	8	-0.42	9	17
NF kappa B1 p50/RelA	-0.11	0.15	-10000	0	-0.38	41	41
SMARCD1	0.011	0.014	-10000	0	-10000	0	0
MDM2	0.099	0.078	0.27	34	-0.22	1	35
GATA3	0.009	0.058	-10000	0	-0.49	5	5
AKT1	0.005	0.002	-10000	0	-10000	0	0
CSF2	-0.22	0.23	-10000	0	-0.54	90	90
GSK3B	0.012	0.007	-10000	0	-10000	0	0
NR1I3	0.024	0.16	0.47	12	-0.79	4	16
CSN2	0.15	0.15	0.42	27	-0.49	2	29
BRG1/BAF155/BAF170/BAF60A	0.029	0.046	-10000	0	-0.37	1	1
NFATC1	0.008	0.047	-10000	0	-0.44	5	5
POU2F1	0.012	0.022	-10000	0	-10000	0	0
CDKN1A	0.024	0.09	-10000	0	-1.3	2	2
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.007	-10000	0	-10000	0	0
SFN	0.01	0.03	-10000	0	-0.44	2	2
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.11	0.11	0.33	14	-0.35	2	16
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.025	0.15	0.46	12	-0.71	2	14
JUN	-0.29	0.17	-10000	0	-0.54	85	85
IL4	-0.099	0.12	-10000	0	-0.48	7	7
CDK5R1	0.011	0.035	-10000	0	-0.72	1	1
PRKACA	0.012	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.31	0.24	-10000	0	-0.6	126	126
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.11	0.1	0.33	13	-0.35	1	14
cortisol/GR alpha (monomer)	0.3	0.27	0.62	119	-0.64	1	120
NCOA2	0.011	0.021	-10000	0	-0.44	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.095	0.067	-10000	0	-0.51	7	7
AP-1/NFAT1-c-4	-0.48	0.27	-10000	0	-0.79	142	142
AFP	-0.22	0.19	-10000	0	-0.72	39	39
SUV420H1	0.012	0	-10000	0	-10000	0	0
IRF1	0.16	0.13	0.45	20	-10000	0	20
TP53	0.029	0.032	-10000	0	-0.45	2	2
PPP5C	0.012	0	-10000	0	-10000	0	0
KRT17	-0.64	0.3	-10000	0	-0.77	353	353
KRT14	-0.15	0.25	0.42	2	-0.87	31	33
TBP	0.02	0.008	-10000	0	-10000	0	0
CREBBP	0.033	0.076	0.31	8	-10000	0	8
HDAC1	0.012	0.009	-10000	0	-10000	0	0
HDAC2	0.03	0.024	-10000	0	-10000	0	0
AP-1	-0.49	0.28	-10000	0	-0.8	142	142
MAPK14	0.012	0.006	-10000	0	-10000	0	0
MAPK10	-0.051	0.16	-10000	0	-0.43	65	65
MAPK11	0.009	0.05	-10000	0	-0.74	2	2
KRT5	-0.39	0.31	-10000	0	-0.82	120	120
interleukin-1 receptor activity	0.018	0.024	-10000	0	-10000	0	0
NCOA1	0.015	0.001	-10000	0	-10000	0	0
STAT1	0.018	0.035	-10000	0	-0.72	1	1
CGA	-0.1	0.15	-10000	0	-0.62	16	16
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.17	0.2	0.39	148	-0.41	8	156
MAPK3	0.012	0.022	-10000	0	-0.44	1	1
MAPK1	0.012	0.006	-10000	0	-10000	0	0
ICAM1	-0.19	0.22	-10000	0	-0.59	61	61
NFKB1	-0.061	0.081	-10000	0	-10000	0	0
MAPK8	-0.21	0.15	-10000	0	-0.44	75	75
MAPK9	0.012	0.006	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.008	0.17	0.49	14	-0.6	5	19
BAX	0.029	0.029	-10000	0	-10000	0	0
POMC	-0.16	0.28	-10000	0	-1.3	20	20
EP300	0.035	0.078	0.31	8	-10000	0	8
cortisol/GR alpha (dimer)/p53	0.27	0.22	0.56	95	-0.55	1	96
proteasomal ubiquitin-dependent protein catabolic process	0.07	0.061	0.24	8	-10000	0	8
SGK1	0.037	0.29	0.4	1	-1.3	21	22
IL13	-0.25	0.2	-10000	0	-0.78	28	28
IL6	-0.26	0.33	-10000	0	-0.81	98	98
PRKACG	0.002	0.035	-10000	0	-0.73	1	1
IL5	-0.21	0.16	-10000	0	-0.7	18	18
IL2	-0.32	0.21	-10000	0	-0.64	79	79
CDK5	0.013	0.004	-10000	0	-10000	0	0
PRKACB	-0.047	0.15	-10000	0	-0.44	60	60
HSP90AA1	0.012	0	-10000	0	-10000	0	0
IL8	-0.42	0.37	-10000	0	-0.7	269	269
CDK5R1/CDK5	0.017	0.028	-10000	0	-0.54	1	1
NF kappa B1 p50/RelA/PKAc	-0.09	0.13	-10000	0	-0.43	12	12
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.26	0.21	0.53	85	-0.5	1	86
SMARCA4	0.011	0.013	-10000	0	-10000	0	0
chromatin remodeling	0.14	0.18	0.37	57	-0.49	13	70
NF kappa B1 p50/RelA/Cbp	-0.047	0.13	0.36	3	-0.42	5	8
JUN (dimer)	-0.28	0.17	-10000	0	-0.54	85	85
YWHAH	0.012	0	-10000	0	-10000	0	0
VIPR1	-0.12	0.21	-10000	0	-0.72	34	34
NR3C1	0.15	0.19	0.44	59	-0.42	18	77
NR4A1	-0.013	0.14	-10000	0	-0.57	24	24
TIF2/SUV420H1	0.018	0.015	-10000	0	-0.3	1	1
MAPKKK cascade	0.013	0.16	0.48	14	-0.57	5	19
cortisol/GR alpha (dimer)/Src-1	0.27	0.22	0.56	93	-0.55	1	94
PBX1	0.001	0.072	-10000	0	-0.44	11	11
POU1F1	-0.001	0.047	-10000	0	-0.88	1	1
SELE	-0.26	0.33	-10000	0	-0.83	93	93
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.14	0.18	0.38	55	-0.5	13	68
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.26	0.21	0.53	85	-0.5	1	86
mol:cortisol	0.17	0.15	0.35	135	-0.22	3	138
MMP1	-0.45	0.28	-10000	0	-0.65	296	296

×

HIF-1-alpha transcription factor network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.44	0.34	-9999	-1	54	54
HDAC7	0.013	0.003	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.33	0.25	-9999	-0.86	24	24
SMAD4	0.011	0.03	-9999	-0.43	2	2
ID2	-0.44	0.34	-9999	-1	53	53
AP1	0.015	0.039	-9999	-10000	0	0
ABCG2	-0.62	0.37	-9999	-1.1	110	110
HIF1A	-0.068	0.049	-9999	-10000	0	0
TFF3	-0.45	0.35	-9999	-1.1	54	54
GATA2	0.003	0.069	-9999	-0.44	11	11
AKT1	-0.067	0.055	-9999	-10000	0	0
response to hypoxia	-0.084	0.056	-9999	-10000	0	0
MCL1	-0.44	0.34	-9999	-1	53	53
NDRG1	-0.44	0.34	-9999	-1.1	50	50
SERPINE1	-0.52	0.41	-9999	-1.1	96	96
FECH	-0.44	0.34	-9999	-1.1	48	48
FURIN	-0.44	0.34	-9999	-1	55	55
NCOA2	0.012	0.021	-9999	-0.44	1	1
EP300	-0.064	0.071	-9999	-0.35	8	8
HMOX1	-0.45	0.34	-9999	-1.1	58	58
BHLHE40	-0.44	0.34	-9999	-1.1	56	56
BHLHE41	-0.45	0.35	-9999	-1.1	55	55
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.063	0.066	-9999	-10000	0	0
ENG	-0.048	0.069	-9999	-10000	0	0
JUN	0.013	0.001	-9999	-10000	0	0
RORA	-0.45	0.34	-9999	-1.1	51	51
ABCB1	-0.32	0.45	-9999	-1.2	97	97
TFRC	-0.44	0.34	-9999	-1.1	46	46
CXCR4	-0.44	0.34	-9999	-1.1	51	51
TF	-0.47	0.36	-9999	-1.1	53	53
CITED2	-0.44	0.34	-9999	-1.1	51	51
HIF1A/ARNT	-0.49	0.39	-9999	-1.2	58	58
LDHA	-0.053	0.042	-9999	-10000	0	0
ETS1	-0.44	0.34	-9999	-1	55	55
PGK1	-0.44	0.34	-9999	-1.1	47	47
NOS2	-0.46	0.36	-9999	-1.1	55	55
ITGB2	-0.45	0.34	-9999	-1.1	55	55
ALDOA	-0.44	0.34	-9999	-1.1	42	42
Cbp/p300/CITED2	-0.42	0.35	-9999	-1.1	44	44
FOS	0.006	0.055	-9999	-0.44	7	7
HK2	-0.44	0.34	-9999	-1.1	42	42
SP1	0.009	0.029	-9999	-10000	0	0
GCK	-0.11	0.2	-9999	-1.3	10	10
HK1	-0.44	0.34	-9999	-1	53	53
NPM1	-0.44	0.34	-9999	-1.1	42	42
EGLN1	-0.44	0.34	-9999	-1.1	47	47
CREB1	0.019	0	-9999	-10000	0	0
PGM1	-0.44	0.34	-9999	-1.1	49	49
SMAD3	0.01	0.036	-9999	-0.43	3	3
EDN1	-0.048	0.12	-9999	-0.92	4	4
IGFBP1	-0.51	0.4	-9999	-1.1	91	91
VEGFA	-0.28	0.24	-9999	-0.88	10	10
HIF1A/JAB1	-0.034	0.029	-9999	-10000	0	0
CP	-0.54	0.38	-9999	-1.1	82	82
CXCL12	-0.48	0.37	-9999	-1.1	75	75
COPS5	0.013	0.001	-9999	-10000	0	0
SMAD3/SMAD4	0.017	0.033	-9999	-0.3	5	5
BNIP3	-0.44	0.34	-9999	-1.1	49	49
EGLN3	-0.44	0.34	-9999	-1	57	57
CA9	-0.72	0.4	-9999	-1.1	169	169
TERT	-0.48	0.38	-9999	-1.1	65	65
ENO1	-0.44	0.34	-9999	-1.1	46	46
PFKL	-0.44	0.34	-9999	-1	53	53
NCOA1	0.012	0	-9999	-10000	0	0
ADM	-0.44	0.34	-9999	-1	53	53
ARNT	-0.07	0.053	-9999	-0.5	1	1
HNF4A	0.014	0.012	-9999	-10000	0	0
ADFP	-0.45	0.34	-9999	-1	56	56
SLC2A1	-0.29	0.27	-9999	-0.98	18	18
LEP	-0.46	0.36	-9999	-1.1	62	62
HIF1A/ARNT/Cbp/p300	-0.34	0.27	-9999	-0.89	25	25
EPO	-0.24	0.19	-9999	-0.88	3	3
CREBBP	-0.064	0.071	-9999	-0.35	8	8
HIF1A/ARNT/Cbp/p300/HDAC7	-0.33	0.26	-9999	-0.93	20	20
PFKFB3	-0.44	0.34	-9999	-1.1	48	48
NT5E	-0.44	0.34	-9999	-1.1	55	55

×

Visual signal transduction: Rods

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
mol:K +	0.012	0	-9999	-10000	0	0
GNAT1/GTP	0	0	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.001	0.039	-9999	-0.48	3	3
PDE6G/GNAT1/GTP	-0.011	0.068	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0	0	-9999	-10000	0	0
GRK1	-0.001	0.049	-9999	-0.73	2	2
CNG Channel	-0.18	0.16	-9999	-0.45	91	91
mol:Na +	-0.07	0.14	-9999	-0.45	42	42
mol:ADP	-0.001	0.048	-9999	-0.73	2	2
RGS9-1/Gbeta5/R9AP	-0.022	0.1	-9999	-0.47	2	2
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.069	0.15	-9999	-0.46	42	42
CNGB1	-0.049	0.14	-9999	-0.44	56	56
RDH5	-0.029	0.13	-9999	-0.44	42	42
SAG	0.002	0.005	-9999	-10000	0	0
mol:Ca2+	-0.046	0.15	-9999	-0.63	12	12
Na + (4 Units)	-0.065	0.14	-9999	-0.61	12	12
RGS9	-0.061	0.16	-9999	-0.44	74	74
GNB1/GNGT1	-0.14	0.25	-9999	-0.55	127	127
GNAT1/GDP	-0.018	0.088	-9999	-0.41	2	2
GUCY2D	-0.017	0.14	-9999	-0.73	16	16
GNGT1	-0.2	0.33	-9999	-0.73	127	127
GUCY2F	-0.001	0.034	-9999	-0.73	1	1
GNB5	0.012	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.14	0.14	-9999	-0.44	37	37
mol:11-cis-retinal	-0.029	0.13	-9999	-0.44	42	42
mol:cGMP	-0.017	0.13	-9999	-0.46	34	34
GNB1	0.012	0	-9999	-10000	0	0
Rhodopsin	-0.023	0.1	-9999	-0.32	45	45
SLC24A1	0.012	0	-9999	-10000	0	0
CNGA1	-0.032	0.13	-9999	-0.44	45	45
Metarhodopsin II	-0.003	0.054	-9999	-0.55	4	4
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.017	0.13	-9999	-0.47	34	34
RGS9BP	0.007	0.049	-9999	-0.73	2	2
Metarhodopsin II/Transducin	-0.062	0.12	-9999	-0.24	128	128
GCAP Family/Ca ++	-0.007	0.095	-9999	-0.44	21	21
PDE6A/B	-0.18	0.17	-9999	-0.32	277	277
mol:Pi	-0.022	0.1	-9999	-0.47	2	2
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.11	0.2	-9999	-0.44	127	127
PDE6B	-0.01	0.096	-9999	-0.44	22	22
PDE6A	-0.26	0.22	-9999	-0.44	272	272
PDE6G	-0.019	0.11	-9999	-0.44	32	32
RHO	-0.004	0.059	-9999	-0.73	3	3
PDE6	-0.16	0.16	-9999	-0.44	74	74
GUCA1A	-0.02	0.14	-9999	-0.73	18	18
GC2/GCAP Family	-0.008	0.1	-9999	-0.46	21	21
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.007	0.06	-9999	-0.73	3	3

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.006	0.11	-9999	-0.47	21	21
EPHB2	0.009	0.049	-9999	-0.73	2	2
Syndecan-2/TACI	-0.093	0.13	-9999	-0.25	193	193
LAMA1	-0.11	0.2	-9999	-0.44	128	128
Syndecan-2/alpha2 ITGB1	0.031	0.031	-9999	-0.4	1	1
HRAS	0.011	0.021	-9999	-0.44	1	1
Syndecan-2/CASK	0.012	0.012	-9999	-0.25	1	1
ITGA5	0.007	0.06	-9999	-0.73	3	3
BAX	0.032	0.011	-9999	-10000	0	0
EPB41	0.012	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0.018	0.019	-9999	-10000	0	0
LAMA3	0.007	0.054	-9999	-0.5	5	5
EZR	0.012	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.004	0.075	-9999	-0.63	6	6
Syndecan-2/MMP2	0.016	0.047	-9999	-0.47	3	3
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.018	0	-9999	-10000	0	0
dendrite morphogenesis	0.019	0.035	-9999	-0.47	2	2
Syndecan-2/GM-CSF	-0.17	0.24	-9999	-0.47	179	179
determination of left/right symmetry	0.016	0.015	-9999	-0.3	1	1
Syndecan-2/PKC delta	0.021	0.012	-9999	-0.24	1	1
GNB2L1	0.012	0	-9999	-10000	0	0
MAPK3	-0.15	0.22	-9999	-0.43	178	178
MAPK1	-0.15	0.22	-9999	-0.43	178	178
Syndecan-2/RACK1	0.026	0.015	-9999	-10000	0	0
NF1	0.012	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.016	0.015	-9999	-0.3	1	1
ITGA2	0.012	0	-9999	-10000	0	0
MAPK8	0.028	0.013	-9999	-10000	0	0
Syndecan-2/alpha2/beta1 Integrin	-0.03	0.1	-9999	-10000	0	0
Syndecan-2/Kininogen	-0.041	0.11	-9999	-0.48	1	1
ITGB1	0.012	0	-9999	-10000	0	0
SRC	0.03	0.014	-9999	-10000	0	0
Syndecan-2/CASK/Protein 4.1	0.019	0.011	-9999	-10000	0	0
extracellular matrix organization	0.02	0.026	-9999	-0.36	2	2
actin cytoskeleton reorganization	-0.006	0.11	-9999	-0.47	21	21
Syndecan-2/Caveolin-2/Ras	0.022	0.05	-9999	-0.43	5	5
Syndecan-2/Laminin alpha3	0.018	0.036	-9999	-0.47	1	1
Syndecan-2/RasGAP	0.031	0.014	-9999	-10000	0	0
alpha5/beta1 Integrin	0.015	0.046	-9999	-0.55	3	3
PRKCD	0.012	0	-9999	-10000	0	0
Syndecan-2 dimer	0.019	0.035	-9999	-0.47	2	2
GO:0007205	0.003	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.037	0.014	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
SDCBP	0.01	0.03	-9999	-0.44	2	2
TNFRSF13B	-0.18	0.22	-9999	-0.44	193	193
RASA1	0.012	0.001	-9999	-10000	0	0
alpha2/beta1 Integrin	0.018	0	-9999	-10000	0	0
Syndecan-2/Synbindin	0.021	0.012	-9999	-10000	0	0
TGFB1	0.011	0.035	-9999	-0.73	1	1
CASP3	0.027	0.011	-9999	-10000	0	0
FN1	-0.03	0.16	-9999	-0.65	29	29
Syndecan-2/IL8	-0.27	0.24	-9999	-0.47	267	267
SDC2	0.016	0.015	-9999	-0.3	1	1
KNG1	-0.092	0.19	-9999	-0.44	103	103
Syndecan-2/Neurofibromin	0.021	0.012	-9999	-0.24	1	1
TRAPPC4	0.012	0	-9999	-10000	0	0
CSF2	-0.28	0.36	-9999	-0.73	178	178
Syndecan-2/TGFB1	0.02	0.026	-9999	-0.36	2	2
Syndecan-2/Syntenin/PI-4-5-P2	0.018	0.02	-9999	-10000	0	0
Syndecan-2/Ezrin	0.028	0.011	-9999	-10000	0	0
PRKACA	0.027	0.011	-9999	-10000	0	0
angiogenesis	-0.27	0.24	-9999	-0.47	267	267
MMP2	0.004	0.07	-9999	-0.58	6	6
IL8	-0.42	0.37	-9999	-0.73	267	267
calcineurin-NFAT signaling pathway	-0.093	0.13	-9999	-0.25	193	193

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.002	0.02	-10000	0	-10000	0	0
HDAC1	0.009	0.004	-10000	0	-10000	0	0
AES	0.012	0.001	-10000	0	-10000	0	0
FBXW11	0.012	0	-10000	0	-10000	0	0
DTX1	0.007	0.047	-10000	0	-0.44	5	5
LRP6/FZD1	0.018	0.015	-10000	0	-0.3	1	1
TLE1	0.011	0.021	-10000	0	-0.44	1	1
AP1	-0.16	0.14	-10000	0	-0.26	293	293
NCSTN	0.012	0	-10000	0	-10000	0	0
ADAM10	0.012	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.057	0.041	-10000	0	-0.46	1	1
NICD/RBPSUH	0.029	0.014	-10000	0	-10000	0	0
WIF1	-0.13	0.29	-10000	0	-0.73	87	87
NOTCH1	-0.001	0.013	-10000	0	-10000	0	0
PSENEN	0.011	0.021	-10000	0	-0.44	1	1
KREMEN2	-0.071	0.23	-10000	0	-0.73	51	51
DKK1	-0.14	0.3	-10000	0	-0.73	94	94
beta catenin/beta TrCP1	0.13	0.08	0.22	1	-10000	0	1
APH1B	0.012	0.001	-10000	0	-10000	0	0
APH1A	0.012	0	-10000	0	-10000	0	0
AXIN1	-0.04	0.039	-10000	0	-0.42	1	1
CtBP/CBP/TCF1/TLE1/AES	0.019	0.021	-10000	0	-10000	0	0
PSEN1	0.012	0	-10000	0	-10000	0	0
FOS	0.005	0.055	-10000	0	-0.44	7	7
JUN	0.012	0	-10000	0	-10000	0	0
MAP3K7	0.011	0.002	-10000	0	-10000	0	0
CTNNB1	0.13	0.087	0.2	214	-10000	0	214
MAPK3	0.011	0.021	-10000	0	-0.44	1	1
DKK2/LRP6/Kremen 2	-0.12	0.24	-10000	0	-0.5	126	126
HNF1A	0.01	0.029	-10000	0	-0.43	2	2
CTBP1	0.012	0.001	-10000	0	-10000	0	0
MYC	0.017	0.069	-10000	0	-0.53	7	7
NKD1	-0.47	0.36	-10000	0	-0.73	295	295
FZD1	0.011	0.021	-10000	0	-0.44	1	1
NOTCH1 precursor/Deltex homolog 1	0.027	0.027	-10000	0	-10000	0	0
apoptosis	-0.16	0.14	-10000	0	-0.25	293	293
Delta 1/NOTCHprecursor	0.028	0.022	-10000	0	-10000	0	0
DLL1	0.009	0.036	-10000	0	-0.44	3	3
PPARD	0.022	0.062	-10000	0	-1.3	1	1
Gamma Secretase	0.037	0.011	-10000	0	-10000	0	0
APC	-0.047	0.064	-10000	0	-0.45	8	8
DVL1	0.01	0.041	-10000	0	-0.36	1	1
CSNK2A1	0.013	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.13	0.25	-10000	0	-0.51	134	134
LRP6	0.012	0	-10000	0	-10000	0	0
CSNK1A1	0.013	0.001	-10000	0	-10000	0	0
NLK	0.011	0.005	-10000	0	-10000	0	0
CCND1	0.022	0.046	-10000	0	-0.53	3	3
WNT1	0.004	0.06	-10000	0	-0.73	3	3
Axin1/APC/beta catenin	0.069	0.051	-10000	0	-0.43	1	1
DKK2	-0.12	0.29	-10000	0	-0.73	85	85
NOTCH1 precursor/DVL1	-0.006	0.021	-10000	0	-10000	0	0
GSK3B	0.012	0.001	-10000	0	-10000	0	0
FRAT1	0.012	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.003	0.023	-10000	0	-10000	0	0
PPP2R5D	0.2	0.15	0.31	295	-10000	0	295
MAPK1	0.012	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.064	0.18	-10000	0	-0.44	89	89
RBPJ	0.012	0	-10000	0	-10000	0	0
CREBBP	0.015	0.002	-10000	0	-10000	0	0

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.17	0.23	-9999	-0.42	195	195
SMAD6-7/SMURF1	0.025	0.013	-9999	-10000	0	0
NOG	0.007	0.035	-9999	-0.73	1	1
SMAD9	-0.05	0.17	-9999	-0.56	40	40
SMAD4	0.01	0.03	-9999	-0.44	2	2
SMAD5	-0.029	0.11	-9999	-0.35	28	28
BMP7/USAG1	-0.26	0.29	-9999	-0.59	177	177
SMAD5/SKI	-0.021	0.11	-9999	-0.36	14	14
SMAD1	0.031	0.023	-9999	-10000	0	0
BMP2	-0.02	0.12	-9999	-0.44	33	33
SMAD1/SMAD1/SMAD4	-0.001	0.01	-9999	-10000	0	0
BMPR1A	0.012	0	-9999	-10000	0	0
BMPR1B	-0.034	0.17	-9999	-0.63	32	32
BMPR1A-1B/BAMBI	-0.04	0.16	-9999	-0.47	53	53
AHSG	-0.1	0.26	-9999	-0.73	69	69
CER1	-0.025	0.14	-9999	-0.73	18	18
BMP2-4/CER1	-0.046	0.17	-9999	-0.53	41	41
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.041	0.13	-9999	-0.37	40	40
BMP2-4 (homodimer)	-0.036	0.16	-9999	-0.61	24	24
RGMB	0.012	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.014	0.12	-9999	-0.43	22	22
RGMA	-0.085	0.18	-9999	-0.44	99	99
SMURF1	0.012	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.044	0.13	-9999	-0.37	38	38
BMP2-4/USAG1	-0.071	0.17	-9999	-0.54	34	34
SMAD6/SMURF1/SMAD5	-0.021	0.11	-9999	-0.36	14	14
SOSTDC1	-0.072	0.17	-9999	-0.44	85	85
BMP7/BMPR2/BMPR1A-1B	-0.18	0.24	-9999	-0.44	191	191
SKI	0.012	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.02	0.12	-9999	-0.44	33	33
HFE2	0.001	0.035	-9999	-0.73	1	1
ZFYVE16	0.01	0.03	-9999	-0.44	2	2
MAP3K7	0.012	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.022	0.14	-9999	-0.53	24	24
SMAD5/SMAD5/SMAD4	-0.022	0.11	-9999	-0.36	13	13
MAPK1	0.012	0	-9999	-10000	0	0
TAK1/TAB family	-0.055	0.094	-9999	-0.32	34	34
BMP7 (homodimer)	-0.28	0.36	-9999	-0.71	183	183
NUP214	0.012	0	-9999	-10000	0	0
BMP6/FETUA	-0.092	0.22	-9999	-0.51	94	94
SMAD1/SKI	0.036	0.022	-9999	-10000	0	0
SMAD6	0.012	0	-9999	-10000	0	0
CTDSP2	0.012	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.098	0.22	-9999	-0.53	86	86
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.023	0.14	-9999	-0.56	28	28
BMPR2 (homodimer)	0.011	0.021	-9999	-0.44	1	1
GADD34/PP1CA	0.024	0.018	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.017	0.13	-9999	-0.46	32	32
CHRDL1	-0.23	0.22	-9999	-0.44	247	247
ENDOFIN/SMAD1	0.035	0.027	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.045	0.022	-9999	-10000	0	0
SMAD6/SMURF1	0.012	0	-9999	-10000	0	0
BAMBI	-0.04	0.19	-9999	-0.73	32	32
SMURF2	0.011	0.021	-9999	-0.44	1	1
BMP2-4/CHRDL1	-0.16	0.19	-9999	-0.56	44	44
BMP2-4/GREM1	-0.044	0.16	-9999	-0.52	38	38
SMAD7	0.011	0.021	-9999	-0.44	1	1
SMAD8A/SMAD8A/SMAD4	-0.042	0.16	-9999	-0.54	39	39
SMAD1/SMAD6	0.036	0.022	-9999	-10000	0	0
TAK1/SMAD6	0.018	0	-9999	-10000	0	0
BMP7	-0.28	0.36	-9999	-0.71	183	183
BMP6	-0.02	0.12	-9999	-0.44	33	33
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.038	0.12	-9999	-0.35	39	39
PPM1A	0.012	0	-9999	-10000	0	0
SMAD1/SMURF2	0.036	0.025	-9999	-10000	0	0
SMAD7/SMURF1	0.018	0.015	-9999	-0.3	1	1
CTDSPL	0.012	0	-9999	-10000	0	0
PPP1CA	0.012	0	-9999	-10000	0	0
XIAP	0.012	0	-9999	-10000	0	0
CTDSP1	0.012	0	-9999	-10000	0	0
PPP1R15A	0.012	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.063	0.16	-9999	-0.48	44	44
CHRD	0.011	0.021	-9999	-0.44	1	1
BMPR2	0.011	0.021	-9999	-0.44	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.054	0.14	-9999	-0.41	38	38
BMP4	-0.03	0.17	-9999	-0.7	27	27
FST	-0.009	0.099	-9999	-0.46	20	20
BMP2-4/NOG	-0.025	0.14	-9999	-0.53	25	25
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.16	0.22	-9999	-0.42	191	191

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.012	0	-10000	0	-10000	0	0
EPHB2	0.009	0.049	-10000	0	-0.73	2	2
EFNB1	0.012	0.059	-10000	0	-0.55	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.091	0.19	-10000	0	-0.4	118	118
Ephrin B2/EPHB1-2	-0.093	0.2	-10000	0	-0.44	115	115
neuron projection morphogenesis	-0.11	0.17	-10000	0	-0.38	118	118
Ephrin B1/EPHB1-2/Tiam1	-0.1	0.21	-10000	0	-0.43	119	119
DNM1	0.004	0.077	-10000	0	-0.73	5	5
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	0.002	0.068	-10000	0	-0.68	3	3
YES1	-0.01	0.083	-10000	0	-0.9	3	3
Ephrin B1/EPHB1-2/NCK2	-0.081	0.2	-10000	0	-0.41	119	119
PI3K	0.006	0.067	-10000	0	-0.69	3	3
mol:GDP	-0.1	0.2	-10000	0	-0.42	119	119
ITGA2B	-0.02	0.15	-10000	0	-0.73	19	19
endothelial cell proliferation	0.016	0.001	-10000	0	-10000	0	0
FYN	-0.01	0.082	-10000	0	-0.9	3	3
MAP3K7	-0.003	0.07	-10000	0	-0.73	3	3
FGR	-0.012	0.087	-10000	0	-0.8	4	4
TIAM1	-0.03	0.13	-10000	0	-0.44	43	43
PIK3R1	0.012	0	-10000	0	-10000	0	0
RGS3	0.012	0	-10000	0	-10000	0	0
cell adhesion	-0.002	0.1	-10000	0	-0.42	22	22
LYN	-0.01	0.082	-10000	0	-0.9	3	3
Ephrin B1/EPHB1-2/Src Family Kinases	-0.011	0.076	-10000	0	-0.82	3	3
Ephrin B1/EPHB1-2	-0.016	0.074	-10000	0	-0.36	15	15
SRC	-0.011	0.082	-10000	0	-0.89	3	3
ITGB3	0.007	0.047	-10000	0	-0.44	5	5
EPHB1	-0.18	0.32	-10000	0	-0.73	115	115
EPHB4	0.012	0	-10000	0	-10000	0	0
RAC1	0.012	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.017	0.001	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.01	0.12	-10000	0	-0.5	24	24
BLK	-0.073	0.12	-10000	0	-0.54	12	12
HCK	-0.016	0.089	-10000	0	-0.8	4	4
regulation of stress fiber formation	0.08	0.2	0.4	119	-10000	0	119
MAPK8	0.008	0.065	-10000	0	-0.64	3	3
Ephrin B1/EPHB1-2/RGS3	-0.081	0.2	-10000	0	-0.41	119	119
endothelial cell migration	0.002	0.062	-10000	0	-0.62	3	3
NCK2	0.012	0	-10000	0	-10000	0	0
PTPN13	-0.007	0.12	-10000	0	-0.65	15	15
regulation of focal adhesion formation	0.08	0.2	0.4	119	-10000	0	119
chemotaxis	0.08	0.2	0.4	119	-10000	0	119
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
Rac1/GTP	-0.11	0.18	-10000	0	-0.39	117	117
angiogenesis	-0.016	0.074	-10000	0	-0.36	15	15
LCK	-0.013	0.083	-10000	0	-0.89	3	3

×

IL1-mediated signaling events

Figure S23. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S23. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	-0.05	0.18	-9999	-0.55	50	50
PRKCZ	0.012	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.012	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.003	0.067	-9999	-10000	0	0
IRAK/TOLLIP	-0.025	0.14	-9999	-0.43	50	50
IKBKB	0.012	0	-9999	-10000	0	0
IKBKG	0.011	0.021	-9999	-0.44	1	1
IL1 alpha/IL1R2	-0.24	0.27	-9999	-0.48	239	239
IL1A	-0.24	0.35	-9999	-0.73	155	155
IL1B	-0.042	0.18	-9999	-0.55	47	47
IRAK/TRAF6/p62/Atypical PKCs	-0.005	0.13	-9999	-0.56	2	2
IL1R2	-0.083	0.18	-9999	-0.44	97	97
IL1R1	0.005	0.055	-9999	-0.44	7	7
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.002	0.082	-9999	-0.43	2	2
TOLLIP	0.012	0	-9999	-10000	0	0
TICAM2	0.004	0.055	-9999	-0.44	7	7
MAP3K3	0.012	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0.008	0	-9999	-10000	0	0
IKK complex/ELKS	0.018	0.1	-9999	-10000	0	0
JUN	-0.005	0.11	-9999	-0.48	1	1
MAP3K7	0.012	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.008	0.13	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.13	0.22	-9999	-0.43	155	155
PIK3R1	0.012	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.12	0.21	-9999	-0.4	155	155
IL1 beta fragment/IL1R1/IL1RAP	-0.023	0.14	-9999	-0.43	48	48
NFKB1	0.012	0	-9999	-10000	0	0
MAPK8	-0.012	0.12	-9999	-0.35	50	50
IRAK1	-0.035	0.15	-9999	-0.47	50	50
IL1RN/IL1R1	-0.074	0.21	-9999	-0.53	77	77
IRAK4	0.012	0	-9999	-10000	0	0
PRKCI	0.01	0.03	-9999	-0.44	2	2
TRAF6	0.012	0	-9999	-10000	0	0
PI3K	0.018	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.006	0.077	-9999	-0.35	1	1
CHUK	0.012	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.023	0.14	-9999	-0.43	48	48
IL1 beta/IL1R2	-0.087	0.17	-9999	-0.48	50	50
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.018	0.12	-9999	-0.37	50	50
NF kappa B1 p50/RelA	-0.039	0.11	-9999	-10000	0	0
IRAK3	0.001	0.069	-9999	-0.44	11	11
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.012	0.13	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.057	0.12	-9999	-0.44	2	2
IL1 alpha/IL1R1/IL1RAP	-0.15	0.24	-9999	-0.48	155	155
RELA	0.012	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.012	0	-9999	-10000	0	0
MYD88	0.012	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	-0.016	0.13	-9999	-0.4	50	50
IL1RAP	0.012	0	-9999	-10000	0	0
UBE2N	0.012	0	-9999	-10000	0	0
IRAK/TRAF6	-0.074	0.15	-9999	-0.57	13	13
CASP1	0.011	0.021	-9999	-0.44	1	1
IL1RN/IL1R2	-0.14	0.22	-9999	-0.41	167	167
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.014	0.14	-9999	-0.4	48	48
TMEM189-UBE2V1	-0.077	0.23	-9999	-0.72	51	51
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.053	0.12	-9999	-0.38	18	18
PIK3CA	0.012	0.001	-9999	-10000	0	0
IL1RN	-0.1	0.27	-9999	-0.73	70	70
TRAF6/TAK1/TAB1/TAB2	-0.025	0.13	-9999	-0.39	50	50
MAP2K6	-0.018	0.12	-9999	-0.37	50	50

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.019	0.14	-10000	0	-0.6	19	19
IHH	0.004	0.088	-10000	0	-0.49	13	13
SHH Np/Cholesterol/GAS1	-0.098	0.2	-10000	0	-0.48	88	88
LRPAP1	0.012	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.098	0.2	0.48	88	-10000	0	88
SMO/beta Arrestin2	0.014	0.096	-10000	0	-0.54	5	5
SMO	0.009	0.1	-10000	0	-0.54	6	6
AKT1	0.024	0.049	-10000	0	-10000	0	0
ARRB2	0.012	0	-10000	0	-10000	0	0
BOC	0.003	0.062	-10000	0	-0.44	9	9
ADRBK1	0.012	0	-10000	0	-10000	0	0
heart looping	0.009	0.1	-10000	0	-0.53	6	6
STIL	-0.042	0.17	-10000	0	-0.56	6	6
DHH N/PTCH2	0.003	0.069	-10000	0	-0.31	20	20
DHH N/PTCH1	0.014	0.099	-10000	0	-0.52	6	6
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
DHH	-0.007	0.089	-10000	0	-0.44	19	19
PTHLH	0.016	0.16	-10000	0	-0.88	9	9
determination of left/right symmetry	0.009	0.1	-10000	0	-0.53	6	6
PIK3R1	0.012	0	-10000	0	-10000	0	0
skeletal system development	0.017	0.16	-10000	0	-0.87	9	9
IHH N/Hhip	-0.062	0.16	-10000	0	-0.35	100	100
DHH N/Hhip	-0.063	0.15	-10000	0	-0.33	106	106
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.009	0.1	-10000	0	-0.53	6	6
pancreas development	-0.084	0.18	-10000	0	-0.44	98	98
HHAT	0.008	0.042	-10000	0	-0.44	4	4
PI3K	0.018	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.055	0.17	-10000	0	-0.46	65	65
somite specification	0.009	0.1	-10000	0	-0.53	6	6
SHH Np/Cholesterol/PTCH1	-0.049	0.18	-10000	0	-0.5	11	11
SHH Np/Cholesterol/PTCH2	-0.064	0.18	-10000	0	-0.44	83	83
SHH Np/Cholesterol/Megalin	-0.1	0.22	-10000	0	-0.47	113	113
SHH	-0.086	0.22	-10000	0	-0.55	82	82
catabolic process	0.021	0.092	-10000	0	-0.55	5	5
SMO/Vitamin D3	-0.039	0.17	-10000	0	-0.57	7	7
SHH Np/Cholesterol/Hhip	-0.11	0.19	-10000	0	-0.46	85	85
LRP2	-0.058	0.21	-10000	0	-0.73	40	40
receptor-mediated endocytosis	-0.053	0.18	-10000	0	-0.54	19	19
SHH Np/Cholesterol/BOC	-0.067	0.18	-10000	0	-0.44	82	82
SHH Np/Cholesterol/CDO	-0.062	0.18	-10000	0	-0.44	82	82
mesenchymal cell differentiation	0.11	0.19	0.45	85	-10000	0	85
mol:Vitamin D3	-0.047	0.18	-10000	0	-0.5	11	11
IHH N/PTCH2	0.013	0.06	-10000	0	-0.39	5	5
CDON	0.012	0	-10000	0	-10000	0	0
IHH N/PTCH1	0.022	0.093	-10000	0	-0.55	5	5
Megalin/LRPAP1	-0.036	0.16	-10000	0	-0.55	40	40
PTCH2	0.011	0.035	-10000	0	-0.73	1	1
SHH Np/Cholesterol	-0.07	0.18	-10000	0	-0.44	82	82
PTCH1	0.021	0.093	-10000	0	-0.55	5	5
HHIP	-0.084	0.18	-10000	0	-0.44	98	98

×

Calcium signaling in the CD4+ TCR 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.01	0.044	-9999	-0.29	3	3
NFATC2	-0.015	0.057	-9999	-0.27	14	14
NFATC3	-0.007	0.034	-9999	-10000	0	0
CD40LG	-0.14	0.25	-9999	-0.67	33	33
PTGS2	-0.14	0.27	-9999	-0.7	54	54
JUNB	0.01	0.03	-9999	-0.44	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.006	0.021	-9999	-10000	0	0
CaM/Ca2+	-0.006	0.021	-9999	-10000	0	0
CALM1	0.005	0.011	-9999	-10000	0	0
JUN	0.006	0.011	-9999	-10000	0	0
mol:Ca2+	-0.011	0.014	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.004	0.007	-9999	-10000	0	0
FOSL1	-0.47	0.35	-9999	-0.73	297	297
CREM	0.012	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.064	0.15	-9999	-0.53	8	8
FOS	-0.001	0.055	-9999	-0.44	7	7
IFNG	-0.16	0.28	-9999	-0.69	66	66
AP-1/NFAT1-c-4	-0.14	0.26	-9999	-0.64	56	56
FASLG	-0.14	0.24	-9999	-0.69	24	24
NFAT1-c-4/ICER1	-0.039	0.085	-9999	-0.5	1	1
IL2RA	-0.13	0.23	-9999	-0.65	22	22
FKBP12/FK506	0.009	0	-9999	-10000	0	0
CSF2	-0.26	0.36	-9999	-0.65	184	184
JunB/Fra1/NFAT1-c-4	-0.28	0.21	-9999	-0.49	178	178
IL4	-0.13	0.22	-9999	-0.65	16	16
IL2	-0.007	0.012	-9999	-10000	0	0
IL3	-0.018	0.019	-9999	-10000	0	0
FKBP1A	0.012	0	-9999	-10000	0	0
BATF3	0.005	0.072	-9999	-0.67	5	5
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.012	0.001	-9999	-10000	0	0

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.045	0.13	-10000	0	-0.44	4	4
ACTA1	-0.071	0.16	-10000	0	-0.35	112	112
NUMA1	-0.046	0.13	-10000	0	-0.28	104	104
SPTAN1	-0.066	0.16	-10000	0	-0.35	105	105
LIMK1	-0.066	0.16	-10000	0	-0.35	105	105
BIRC3	0.004	0.065	-10000	0	-0.47	8	8
BIRC2	0.012	0.001	-10000	0	-10000	0	0
BAX	0.012	0	-10000	0	-10000	0	0
CASP10	-0.099	0.22	-10000	0	-0.48	108	108
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.012	0	-10000	0	-10000	0	0
PTK2	-0.045	0.13	-10000	0	-0.44	4	4
DIABLO	0.012	0.001	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.065	0.16	-10000	0	-0.34	105	105
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.012	0	-10000	0	-10000	0	0
GSN	-0.071	0.16	-10000	0	-0.35	106	106
MADD	0.012	0	-10000	0	-10000	0	0
TFAP2A	-0.063	0.1	-10000	0	-0.57	3	3
BID	-0.037	0.1	-10000	0	-0.21	108	108
MAP3K1	-0.02	0.063	-10000	0	-0.21	5	5
TRADD	0.012	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.019	0.001	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.066	0.16	-10000	0	-0.35	104	104
CASP9	0.013	0.001	-10000	0	-10000	0	0
DNA repair	0.015	0.049	-10000	0	-0.16	5	5
neuron apoptosis	0.013	0.02	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.057	0.15	-10000	0	-0.56	4	4
APAF1	0.012	0.001	-10000	0	-10000	0	0
CASP6	-0.01	0.079	-10000	0	-10000	0	0
TRAF2	0.011	0.021	-10000	0	-0.44	1	1
ICAD/CAD	-0.059	0.16	-10000	0	-0.56	4	4
CASP7	0.002	0.043	0.26	8	-0.43	1	9
KRT18	0.006	0.024	-10000	0	-10000	0	0
apoptosis	-0.05	0.15	-10000	0	-0.51	4	4
DFFA	-0.066	0.16	-10000	0	-0.35	105	105
DFFB	-0.066	0.16	-10000	0	-0.35	104	104
PARP1	-0.015	0.049	0.16	5	-10000	0	5
actin filament polymerization	0.06	0.15	0.32	102	-10000	0	102
TNF	0.01	0.03	-10000	0	-0.44	2	2
CYCS	-0.027	0.082	-10000	0	-0.22	8	8
SATB1	-0.008	0.08	-10000	0	-10000	0	0
SLK	-0.067	0.16	-10000	0	-0.35	104	104
p15 BID/BAX	-0.027	0.091	-10000	0	-0.3	5	5
CASP2	0.038	0.031	-10000	0	-0.35	1	1
JNK cascade	0.02	0.062	0.21	5	-10000	0	5
CASP3	-0.076	0.17	-10000	0	-0.37	111	111
LMNB2	0.025	0.036	-10000	0	-10000	0	0
RIPK1	0.012	0	-10000	0	-10000	0	0
CASP4	0.012	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.027	0.037	-10000	0	-0.43	1	1
negative regulation of DNA binding	-0.063	0.1	-10000	0	-0.56	3	3
stress fiber formation	-0.066	0.16	-10000	0	-0.34	104	104
GZMB	-0.12	0.25	-10000	0	-0.56	108	108
CASP1	0.014	0.014	-10000	0	-0.29	1	1
LMNB1	0.025	0.036	-10000	0	-10000	0	0
APP	0.013	0.02	-10000	0	-10000	0	0
TNFRSF1A	0.012	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.01	0	-10000	0	-10000	0	0
VIM	-0.052	0.14	-10000	0	-0.5	4	4
LMNA	0.025	0.036	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.034	0.033	-10000	0	-0.38	1	1
LRDD	0.011	0.021	-10000	0	-0.44	1	1
SREBF1	-0.066	0.16	-10000	0	-0.35	105	105
APAF-1/Caspase 9	-0.013	0.031	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	-0.045	0.13	-10000	0	-0.27	104	104
CFL2	-0.061	0.15	-10000	0	-0.32	102	102
GAS2	-0.14	0.23	-10000	0	-0.43	161	161
positive regulation of apoptosis	0.029	0.035	-10000	0	-10000	0	0
PRF1	0.003	0.068	-10000	0	-0.47	9	9

×

Effects of Botulinum toxin

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
STX1A	-0.023	0.13	-9999	-0.56	26	26
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.009	0.059	-9999	-0.55	5	5
STXBP1	0.004	0.077	-9999	-0.73	5	5
ACh/CHRNA1	-0.05	0.094	-9999	-0.31	43	43
RAB3GAP2/RIMS1/UNC13B	0.016	0.053	-9999	-0.47	5	5
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	0.077	-9999	-0.73	5	5
mol:ACh	-0.043	0.06	-9999	-0.11	191	191
RAB3GAP2	0.011	0.021	-9999	-0.44	1	1
STX1A/SNAP25/VAMP2	-0.071	0.11	-9999	-0.38	36	36
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.05	0.094	-9999	-0.31	43	43
UNC13B	0.012	0	-9999	-10000	0	0
CHRNA1	-0.03	0.13	-9999	-0.44	43	43
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.061	0.11	-9999	-0.31	62	62
SNAP25	-0.096	0.13	-9999	-0.26	174	174
VAMP2	0.006	0	-9999	-10000	0	0
SYT1	-0.049	0.15	-9999	-0.44	62	62
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.017	0.12	-9999	-0.48	31	31
STX1A/SNAP25 fragment 1/VAMP2	-0.071	0.11	-9999	-0.38	36	36

×

JNK signaling in the CD4+ TCR pathway

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
LAT/GRAP2/SLP76/HPK1	-0.007	0.11	-9999	-0.45	18	18
MAP4K1	-0.034	0.14	-9999	-0.44	47	47
MAP3K8	0.012	0	-9999	-10000	0	0
PRKCB	-0.09	0.19	-9999	-0.44	104	104
DBNL	0.012	0	-9999	-10000	0	0
CRKL	0.012	0	-9999	-10000	0	0
MAP3K1	0.006	0.095	-9999	-0.38	17	17
JUN	-0.1	0.25	-9999	-0.56	104	104
MAP3K7	0.007	0.095	-9999	-0.38	17	17
GRAP2	-0.006	0.089	-9999	-0.44	19	19
CRK	0.012	0	-9999	-10000	0	0
MAP2K4	0.012	0.096	-9999	-0.38	17	17
LAT	0.009	0.046	-9999	-0.53	3	3
LCP2	0.008	0.042	-9999	-0.44	4	4
MAPK8	-0.11	0.27	-9999	-0.6	104	104
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.001	0.1	-9999	-0.41	17	17
LAT/GRAP2/SLP76/HPK1/HIP-55	0	0.11	-9999	-0.42	18	18

×

TCGA08_p53

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
CDKN2A	-0.12	0.24	-10000	0	-0.56	101	101
TP53	-0.031	0.059	-10000	0	-10000	0	0
Senescence	-0.031	0.059	-10000	0	-10000	0	0
Apoptosis	-0.031	0.059	-10000	0	-10000	0	0
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.058	0.11	0.27	100	-10000	0	100
MDM4	0.012	0	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.017	0.16	-10000	0	-0.8	18	18
NFATC2	-0.024	0.18	-10000	0	-0.64	15	15
NFATC3	-0.021	0.057	-10000	0	-10000	0	0
CD40LG	-0.33	0.36	-10000	0	-0.95	61	61
ITCH	0.04	0.016	-10000	0	-10000	0	0
CBLB	0.039	0.028	-10000	0	-0.52	1	1
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.17	0.27	-10000	0	-0.92	34	34
JUNB	0.01	0.03	-10000	0	-0.44	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	0.033	0.019	-10000	0	-10000	0	0
T cell anergy	0.037	0.046	-10000	0	-10000	0	0
TLE4	-0.003	0.13	-10000	0	-0.57	10	10
Jun/NFAT1-c-4/p21SNFT	-0.16	0.26	-10000	0	-0.95	19	19
AP-1/NFAT1-c-4	-0.35	0.4	-10000	0	-1.1	58	58
IKZF1	-0.041	0.22	-10000	0	-0.69	44	44
T-helper 2 cell differentiation	-0.094	0.18	-10000	0	-0.74	17	17
AP-1/NFAT1	-0.077	0.13	-10000	0	-0.53	7	7
CALM1	0.024	0.011	-10000	0	-10000	0	0
EGR2	-0.06	0.25	-10000	0	-1.2	13	13
EGR3	-0.066	0.26	-10000	0	-1.3	12	12
NFAT1/FOXP3	-0.028	0.19	-10000	0	-0.65	26	26
EGR1	0.012	0.021	-10000	0	-0.43	1	1
JUN	-0.028	0.037	-10000	0	-10000	0	0
EGR4	-0.12	0.28	-10000	0	-0.73	80	80
mol:Ca2+	0.012	0.011	-10000	0	-10000	0	0
GBP3	-0.039	0.21	-10000	0	-0.66	40	40
FOSL1	-0.47	0.35	-10000	0	-0.73	297	297
NFAT1-c-4/MAF/IRF4	-0.15	0.28	-10000	0	-0.99	23	23
DGKA	-0.004	0.14	-10000	0	-0.67	8	8
CREM	0.012	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.081	0.23	-10000	0	-1	14	14
CTLA4	-0.031	0.2	-10000	0	-0.71	27	27
NFAT1-c-4 (dimer)/EGR1	-0.077	0.23	-10000	0	-1	14	14
NFAT1-c-4 (dimer)/EGR4	-0.16	0.28	-10000	0	-0.97	22	22
FOS	-0.035	0.063	-10000	0	-0.45	7	7
IFNG	-0.13	0.25	-10000	0	-0.64	67	67
T cell activation	-0.1	0.16	-10000	0	-0.68	8	8
MAF	0.001	0.072	-10000	0	-0.44	12	12
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.058	0.21	0.97	13	-10000	0	13
TNF	-0.12	0.24	-10000	0	-0.94	15	15
FASLG	-0.14	0.4	-10000	0	-1.3	40	40
TBX21	-0.022	0.12	-10000	0	-0.45	29	29
BATF3	0.005	0.072	-10000	0	-0.67	5	5
PRKCQ	0.005	0.056	-10000	0	-0.44	6	6
PTPN1	-0.001	0.12	-10000	0	-0.57	6	6
NFAT1-c-4/ICER1	-0.08	0.23	-10000	0	-1	14	14
GATA3	0.007	0.054	-10000	0	-0.5	5	5
T-helper 1 cell differentiation	-0.12	0.25	-10000	0	-0.62	67	67
IL2RA	-0.19	0.23	-10000	0	-0.87	31	31
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.001	0.12	-10000	0	-0.53	8	8
E2F1	0.001	0.11	-10000	0	-0.72	10	10
PPARG	0.009	0.036	-10000	0	-0.44	3	3
SLC3A2	-0.001	0.12	-10000	0	-0.57	6	6
IRF4	-0.14	0.21	-10000	0	-0.44	150	150
PTGS2	-0.33	0.38	-10000	0	-1	62	62
CSF2	-0.45	0.46	-10000	0	-0.96	180	180
JunB/Fra1/NFAT1-c-4	-0.35	0.29	-10000	0	-0.88	46	46
IL4	-0.097	0.19	-10000	0	-0.79	16	16
IL5	-0.32	0.35	-10000	0	-0.95	54	54
IL2	-0.11	0.16	-10000	0	-0.69	8	8
IL3	-0.065	0.05	-10000	0	-10000	0	0
RNF128	0.038	0.028	-10000	0	-0.52	1	1
NFATC1	-0.059	0.21	-10000	0	-0.98	13	13
CDK4	0.038	0.13	0.67	5	-10000	0	5
PTPRK	-0.001	0.12	-10000	0	-0.57	6	6
IL8	-0.52	0.46	-10000	0	-0.96	195	195
POU2F1	0.012	0.001	-10000	0	-10000	0	0

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.018	0	-9999	-10000	0	0
Necdin/E2F1	-0.007	0.11	-9999	-0.4	28	28
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.035	0.12	-9999	-0.41	11	11
NGF (dimer)/p75(NTR)/BEX1	-0.13	0.19	-9999	-0.5	58	58
NT-4/5 (dimer)/p75(NTR)	-0.094	0.18	-9999	-0.35	136	136
IKBKB	0.012	0	-9999	-10000	0	0
AKT1	-0.037	0.11	-9999	-0.4	9	9
IKBKG	0.011	0.021	-9999	-0.44	1	1
BDNF	-0.009	0.12	-9999	-0.73	13	13
MGDIs/NGR/p75(NTR)/LINGO1	-0.087	0.18	-9999	-0.55	35	35
FURIN	0.011	0.021	-9999	-0.44	1	1
proBDNF (dimer)/p75(NTR)/Sortilin	-0.061	0.14	-9999	-0.49	13	13
LINGO1	-0.022	0.16	-9999	-0.73	21	21
Sortilin/TRAF6/NRIF	-0.002	0.017	-9999	-10000	0	0
proBDNF (dimer)	-0.009	0.12	-9999	-0.73	13	13
NTRK1	0.005	0.069	-9999	-0.73	4	4
RTN4R	-0.016	0.14	-9999	-0.71	18	18
neuron apoptosis	-0.046	0.14	-9999	-0.5	7	7
IRAK1	0.012	0	-9999	-10000	0	0
SHC1	-0.058	0.13	-9999	-0.48	9	9
ARHGDIA	0.011	0.021	-9999	-0.44	1	1
RhoA/GTP	0.009	0	-9999	-10000	0	0
Gamma Secretase	0.036	0.011	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.047	0.13	-9999	-0.46	10	10
MAGEH1	0.006	0.051	-9999	-0.44	6	6
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.053	0.14	-9999	-0.45	21	21
Mammalian IAPs/DIABLO	0.027	0.037	-9999	-0.43	1	1
proNGF (dimer)	-0.006	0.089	-9999	-0.45	17	17
MAGED1	0.012	0	-9999	-10000	0	0
APP	0.012	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.026	0.15	-9999	-0.73	19	19
ZNF274	0.008	0.042	-9999	-0.44	4	4
RhoA/GDP/RHOGDI	-0.042	0.11	-9999	-0.41	9	9
NGF	-0.006	0.089	-9999	-0.45	17	17
cell cycle arrest	-0.028	0.12	-9999	-0.4	9	9
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.038	0.11	-9999	-0.42	8	8
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.071	0.15	-9999	-0.52	19	19
NCSTN	0.012	0	-9999	-10000	0	0
mol:GTP	-0.091	0.16	-9999	-0.49	31	31
PSENEN	0.011	0.021	-9999	-0.44	1	1
mol:ceramide	-0.046	0.12	-9999	-0.43	9	9
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.025	0.1	-9999	-0.36	8	8
p75(NTR)/beta APP	-0.066	0.14	-9999	-10000	0	0
BEX1	-0.12	0.2	-9999	-0.44	127	127
mol:GDP	-0.066	0.13	-9999	-0.49	9	9
NGF (dimer)	-0.5	0.18	-9999	-0.52	442	442
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.072	0.17	-9999	-0.51	35	35
PIK3R1	0.012	0	-9999	-10000	0	0
RAC1/GTP	-0.048	0.11	-9999	-0.42	9	9
MYD88	0.012	0	-9999	-10000	0	0
CHUK	0.012	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.091	0.16	-9999	-0.49	31	31
RHOB	0.012	0	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
MAGE-G1/E2F1	0.006	0.083	-9999	-0.55	10	10
NT3 (dimer)	0.004	0.059	-9999	-0.44	8	8
TP53	-0.034	0.12	-9999	-0.39	15	15
PRDM4	-0.046	0.12	-9999	-0.44	9	9
BDNF (dimer)	-0.84	0.25	-9999	-0.84	455	455
PIK3CA	0.012	0.001	-9999	-10000	0	0
SORT1	0.012	0	-9999	-10000	0	0
activation of caspase activity	-0.037	0.12	-9999	-0.41	11	11
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.043	0.12	-9999	-0.44	9	9
RHOC	0.012	0	-9999	-10000	0	0
XIAP	0.012	0	-9999	-10000	0	0
MAPK10	-0.066	0.17	-9999	-0.45	41	41
DIABLO	0.012	0.001	-9999	-10000	0	0
SMPD2	-0.046	0.12	-9999	-0.44	9	9
APH1B	0.012	0.001	-9999	-10000	0	0
APH1A	0.012	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.057	0.13	-9999	-0.48	9	9
PSEN1	0.012	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0.018	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.072	0.15	-9999	-0.31	126	126
MAPK8	-0.036	0.14	-9999	-0.4	9	9
MAPK9	-0.036	0.14	-9999	-0.4	11	11
APAF1	0.012	0.001	-9999	-10000	0	0
NTF3	0.004	0.059	-9999	-0.44	8	8
NTF4	-0.026	0.15	-9999	-0.73	19	19
NDN	-0.006	0.089	-9999	-0.44	19	19
RAC1/GDP	0.009	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.078	0.12	-9999	-0.58	1	1
p75 CTF/Sortilin/TRAF6/NRIF	0.03	0.023	-9999	-10000	0	0
RhoA-B-C/GTP	-0.091	0.16	-9999	-0.49	31	31
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.039	0.12	-9999	-0.42	15	15
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.047	0.13	-9999	-0.45	13	13
PRKACB	-0.047	0.15	-9999	-0.44	60	60
proBDNF (dimer)/p75 ECD	0.002	0.095	-9999	-0.55	13	13
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	0.004	0.065	-9999	-0.47	8	8
BIRC2	0.012	0.001	-9999	-10000	0	0
neuron projection morphogenesis	-0.059	0.15	-9999	-0.41	26	26
BAD	-0.047	0.15	-9999	-0.43	11	11
RIPK2	0.012	0	-9999	-10000	0	0
NGFR	-0.11	0.2	-9999	-0.44	121	121
CYCS	-0.037	0.11	-9999	-0.41	9	9
ADAM17	0.012	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.043	0.12	-9999	-0.44	9	9
BCL2L11	-0.046	0.15	-9999	-0.43	11	11
BDNF (dimer)/p75(NTR)	-0.082	0.16	-9999	-0.33	133	133
PI3K	-0.043	0.12	-9999	-0.44	9	9
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.043	0.12	-9999	-0.44	9	9
NDNL2	0.012	0.001	-9999	-10000	0	0
YWHAE	0.012	0	-9999	-10000	0	0
PRKCI	0.01	0.03	-9999	-0.44	2	2
NGF (dimer)/p75(NTR)	-0.078	0.16	-9999	-0.56	9	9
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.043	0.12	-9999	-0.44	9	9
TRAF6	0.012	0	-9999	-10000	0	0
RAC1	0.012	0	-9999	-10000	0	0
PRKCZ	0.012	0	-9999	-10000	0	0
PLG	-0.13	0.29	-9999	-0.73	86	86
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.058	0.14	-9999	-0.47	9	9
SQSTM1	0.012	0	-9999	-10000	0	0
NGFRAP1	0.01	0.03	-9999	-0.44	2	2
CASP3	-0.043	0.14	-9999	-0.4	11	11
E2F1	-0.004	0.11	-9999	-0.73	10	10
CASP9	0.012	0	-9999	-10000	0	0
IKK complex	-0.045	0.082	-9999	-0.4	9	9
NGF (dimer)/TRKA	-0.001	0.082	-9999	-0.36	21	21
MMP7	-0.7	0.14	-9999	-0.73	439	439
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.036	0.12	-9999	-0.41	11	11
MMP3	-0.6	0.29	-9999	-0.73	374	374
APAF-1/Caspase 9	-0.043	0.073	-9999	-0.46	1	1

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.007	0.1	-9999	-0.5	14	14
alphaM/beta2 Integrin/GPIbA	-0.007	0.096	-9999	-0.44	14	14
alphaM/beta2 Integrin/proMMP-9	-0.043	0.16	-9999	-0.49	49	49
PLAUR	0.012	0	-9999	-10000	0	0
HMGB1	0.007	0.017	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.002	0.09	-9999	-0.45	12	12
AGER	0.006	0.04	-9999	-0.78	1	1
RAP1A	0.012	0	-9999	-10000	0	0
SELPLG	0.009	0.036	-9999	-0.44	3	3
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.007	0.11	-9999	-0.46	13	13
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.051	0.2	-9999	-0.71	40	40
CYR61	0.006	0.069	-9999	-0.73	4	4
TLN1	0.012	0	-9999	-10000	0	0
Rap1/GTP	-0.061	0.098	-9999	-0.37	23	23
RHOA	0.012	0	-9999	-10000	0	0
P-selectin oligomer	-0.049	0.15	-9999	-0.44	62	62
MYH2	-0.057	0.14	-9999	-0.42	31	31
MST1R	0.012	0	-9999	-10000	0	0
leukocyte activation during inflammatory response	-0.059	0.15	-9999	-0.43	45	45
APOB	-0.072	0.2	-9999	-0.52	69	69
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.004	0.07	-9999	-0.58	6	6
JAM3	0.012	0	-9999	-10000	0	0
GP1BA	0.004	0.055	-9999	-0.44	7	7
alphaM/beta2 Integrin/CTGF	-0.006	0.1	-9999	-0.48	14	14
alphaM/beta2 Integrin	-0.056	0.13	-9999	-0.38	40	40
JAM3 homodimer	0.012	0	-9999	-10000	0	0
ICAM2	0.012	0	-9999	-10000	0	0
ICAM1	0.011	0.035	-9999	-0.73	1	1
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.056	0.13	-9999	-0.38	40	40
cell adhesion	-0.007	0.096	-9999	-0.44	14	14
NFKB1	-0.017	0.15	-9999	-0.65	5	5
THY1	-0.017	0.14	-9999	-0.73	18	18
RhoA/GDP	0.009	0	-9999	-10000	0	0
Lipoprotein(a)	-0.055	0.15	-9999	-0.35	82	82
alphaM/beta2 Integrin/LRP/tPA	0.004	0.086	-9999	-0.44	9	9
IL6	-0.063	0.24	-9999	-0.58	78	78
ITGB2	-0.002	0.067	-9999	-0.44	10	10
elevation of cytosolic calcium ion concentration	-0.029	0.15	-9999	-0.44	46	46
alphaM/beta2 Integrin/JAM2/JAM3	-0.05	0.15	-9999	-0.52	24	24
JAM2	-0.095	0.19	-9999	-0.44	109	109
alphaM/beta2 Integrin/ICAM1	-0.054	0.17	-9999	-0.42	79	79
alphaM/beta2 Integrin/uPA/Plg	-0.12	0.22	-9999	-0.45	130	130
RhoA/GTP	-0.06	0.14	-9999	-0.45	30	30
positive regulation of phagocytosis	-0.058	0.12	-9999	-0.49	22	22
Ron/MSP	-0.069	0.2	-9999	-0.55	70	70
alphaM/beta2 Integrin/uPAR/uPA	-0.029	0.15	-9999	-0.45	46	46
alphaM/beta2 Integrin/uPAR	-0.002	0.09	-9999	-0.45	12	12
PLAU	-0.046	0.2	-9999	-0.73	36	36
PLAT	0.009	0.036	-9999	-0.44	3	3
actin filament polymerization	-0.054	0.13	-9999	-0.41	31	31
MST1	-0.1	0.27	-9999	-0.73	70	70
alphaM/beta2 Integrin/lipoprotein(a)	-0.056	0.15	-9999	-0.43	45	45
TNF	-0.01	0.14	-9999	-0.71	5	5
RAP1B	0.012	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.041	0.16	-9999	-0.48	48	48
fibrinolysis	-0.12	0.21	-9999	-0.45	130	130
HCK	0.001	0.072	-9999	-0.44	12	12
dendritic cell antigen processing and presentation	-0.056	0.13	-9999	-0.38	40	40
VTN	-0.012	0.13	-9999	-0.73	14	14
alphaM/beta2 Integrin/CYR61	-0.006	0.1	-9999	-0.46	16	16
LPA	-0.016	0.13	-9999	-0.73	14	14
LRP1	0.01	0.03	-9999	-0.44	2	2
cell migration	-0.037	0.16	-9999	-0.48	47	47
FN1	-0.03	0.16	-9999	-0.65	29	29
alphaM/beta2 Integrin/Thy1	-0.021	0.13	-9999	-0.47	30	30
MPO	-0.023	0.16	-9999	-0.73	21	21
KNG1	-0.092	0.19	-9999	-0.44	103	103
RAP1/GDP	0.017	0	-9999	-10000	0	0
ROCK1	-0.051	0.14	-9999	-0.42	30	30
ELA2	0	0	-9999	-10000	0	0
PLG	-0.13	0.29	-9999	-0.73	86	86
CTGF	0.006	0.069	-9999	-0.73	4	4
alphaM/beta2 Integrin/Hck	-0.008	0.11	-9999	-0.52	16	16
ITGAM	-0.018	0.1	-9999	-0.44	26	26
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.027	0.13	-9999	-0.53	17	17
HP	-0.031	0.17	-9999	-0.73	25	25
leukocyte adhesion	-0.058	0.16	-9999	-0.55	19	19
SELP	-0.049	0.15	-9999	-0.44	62	62

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.012	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.001	0.079	-9999	-10000	0	0
Syndecan-3/Neurocan	0.009	0.029	-9999	-0.4	2	2
POMC	-0.008	0.097	-9999	-0.47	19	19
EGFR	0.011	0.021	-9999	-0.44	1	1
Syndecan-3/EGFR	0.022	0.011	-9999	-10000	0	0
AGRP	0	0.06	-9999	-0.73	3	3
NCSTN	0.012	0	-9999	-10000	0	0
PSENEN	0.011	0.021	-9999	-0.44	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.012	0.001	-9999	-10000	0	0
APH1A	0.012	0	-9999	-10000	0	0
NCAN	0.003	0.049	-9999	-0.73	2	2
long-term memory	0.029	0.003	-9999	-10000	0	0
Syndecan-3/IL8	-0.22	0.21	-9999	-0.4	267	267
PSEN1	0.012	0	-9999	-10000	0	0
Src/Cortactin	0.018	0	-9999	-10000	0	0
FYN	0.012	0	-9999	-10000	0	0
limb bud formation	0	0.002	-9999	-10000	0	0
MC4R	-0.003	0.069	-9999	-0.73	4	4
SRC	0.012	0	-9999	-10000	0	0
PTN	-0.064	0.17	-9999	-0.44	78	78
FGFR/FGF/Syndecan-3	0	0.002	-9999	-10000	0	0
neuron projection morphogenesis	-0.014	0.075	-9999	-0.35	2	2
Syndecan-3/AgRP	0.006	0.035	-9999	-0.4	3	3
Syndecan-3/AgRP/MC4R	0.006	0.057	-9999	-0.46	6	6
Fyn/Cortactin	0.018	0	-9999	-10000	0	0
SDC3	0	0.002	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.22	0.2	-9999	-0.39	267	267
IL8	-0.42	0.37	-9999	-0.73	267	267
Syndecan-3/Fyn/Cortactin	0.029	0.003	-9999	-10000	0	0
Syndecan-3/CASK	0	0.002	-9999	-10000	0	0
alpha-MSH/MC4R	-0.008	0.087	-9999	-0.37	23	23
Gamma Secretase	0.036	0.011	-9999	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.013	0.015	-10000	0	-10000	0	0
AES	0.013	0.013	-10000	0	-10000	0	0
FBXW11	0.012	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.019	0.015	-10000	0	-0.3	1	1
SMAD4	0.01	0.03	-10000	0	-0.44	2	2
DKK2	-0.12	0.29	-10000	0	-0.73	85	85
TLE1	0.012	0.023	-10000	0	-0.41	1	1
MACF1	0.013	0	-10000	0	-10000	0	0
CTNNB1	0.064	0.089	0.25	8	-10000	0	8
WIF1	-0.13	0.29	-10000	0	-0.73	87	87
beta catenin/RanBP3	0.023	0.1	0.34	18	-10000	0	18
KREMEN2	-0.071	0.23	-10000	0	-0.73	51	51
DKK1	-0.14	0.3	-10000	0	-0.73	94	94
beta catenin/beta TrCP1	0.068	0.085	0.24	6	-10000	0	6
FZD1	0.012	0.021	-10000	0	-0.44	1	1
AXIN2	-0.041	0.17	-10000	0	-0.53	49	49
AXIN1	0.012	0.021	-10000	0	-0.44	1	1
RAN	0.012	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.022	0.042	-10000	0	-0.53	1	1
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.043	0.082	-10000	0	-0.41	1	1
Axin1/APC/GSK3	0.1	0.062	-10000	0	-0.35	1	1
Axin1/APC/GSK3/beta catenin/Macf1	0.055	0.055	-10000	0	-10000	0	0
HNF1A	0.011	0.033	-10000	0	-0.44	2	2
CTBP1	0.013	0.013	-10000	0	-10000	0	0
MYC	-0.001	0.08	-10000	0	-0.56	7	7
RANBP3	0.012	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.12	0.24	-10000	0	-0.5	126	126
NKD1	-0.47	0.36	-10000	0	-0.73	295	295
TCF4	0.012	0.025	-10000	0	-0.44	1	1
TCF3	0.013	0.013	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.028	0.041	-10000	0	-0.43	3	3
Ran/GTP	0.009	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.015	0.1	0.56	1	-10000	0	1
LEF1	-0.076	0.24	-10000	0	-0.72	55	55
DVL1	0.042	0.034	-10000	0	-0.26	1	1
CSNK2A1	0.013	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.041	0.091	-10000	0	-0.42	2	2
DKK1/LRP6/Kremen 2	-0.13	0.25	-10000	0	-0.51	134	134
LRP6	0.013	0.001	-10000	0	-10000	0	0
CSNK1A1	0.014	0.015	-10000	0	-10000	0	0
NLK	0.012	0.004	-10000	0	-10000	0	0
CCND1	0.003	0.061	-10000	0	-0.55	3	3
WNT1	0.004	0.06	-10000	0	-0.73	3	3
GSK3A	0.013	0.001	-10000	0	-10000	0	0
GSK3B	0.013	0.001	-10000	0	-10000	0	0
FRAT1	0.012	0.001	-10000	0	-10000	0	0
PPP2R5D	0.21	0.15	0.32	295	-10000	0	295
APC	0.025	0.048	-10000	0	-0.4	3	3
WNT1/LRP6/FZD1	0.061	0.077	0.22	86	-10000	0	86
CREBBP	0.013	0.013	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.004	0.12	-9999	-0.52	8	8
MAP3K8	0.013	0.001	-9999	-10000	0	0
FOS	-0.014	0.11	-9999	-0.46	8	8
PRKCA	0.013	0.002	-9999	-10000	0	0
PTPN7	0.004	0.078	-9999	-0.6	7	7
HRAS	0.011	0.021	-9999	-0.44	1	1
PRKCB	-0.089	0.19	-9999	-0.44	104	104
NRAS	0.01	0.03	-9999	-0.44	2	2
RAS family/GTP	0.023	0.02	-9999	-10000	0	0
MAPK3	-0.007	0.085	-9999	-0.54	4	4
MAP2K1	-0.051	0.16	-9999	-0.35	104	104
ELK1	0.013	0.002	-9999	-10000	0	0
BRAF	-0.058	0.16	-9999	-0.35	104	104
mol:GTP	0	0.001	-9999	-0.004	7	7
MAPK1	-0.006	0.083	-9999	-0.6	3	3
RAF1	-0.058	0.16	-9999	-0.35	104	104
KRAS	0.012	0	-9999	-10000	0	0

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.008	0.07	-9999	-0.41	10	10
RGS9BP	0.007	0.049	-9999	-0.73	2	2
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.001	0.049	-9999	-0.73	2	2
mol:Na +	-0.096	0.16	-9999	-0.3	155	155
mol:ADP	0.003	0.06	-9999	-0.7	3	3
GNAT2	0	0.091	-9999	-0.73	7	7
RGS9-1/Gbeta5/R9AP	-0.022	0.1	-9999	-0.47	2	2
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.065	-9999	-0.48	8	8
GRK7	0.004	0.049	-9999	-0.73	2	2
CNGB3	-0.033	0.16	-9999	-0.73	23	23
Cone Metarhodopsin II/X-Arrestin	0	0.037	-9999	-0.56	2	2
mol:Ca2+	-0.13	0.2	-9999	-0.53	64	64
Cone PDE6	-0.017	0.09	-9999	-0.4	3	3
Cone Metarhodopsin II	0.002	0.05	-9999	-0.58	3	3
Na + (4 Units)	-0.13	0.2	-9999	-0.52	64	64
GNAT2/GDP	-0.018	0.1	-9999	-0.41	9	9
GNB5	0.012	0	-9999	-10000	0	0
mol:GMP (4 units)	0.001	0.059	-9999	-0.44	8	8
Cone Transducin	0.009	0.074	-9999	-0.44	10	10
SLC24A2	-0.067	0.22	-9999	-0.73	46	46
GNB3/GNGT2	0.009	0.062	-9999	-0.37	11	11
GNB3	0.006	0.063	-9999	-0.66	4	4
GNAT2/GTP	0	0.07	-9999	-0.56	7	7
CNGA3	-0.13	0.21	-9999	-0.44	138	138
ARR3	0	0.049	-9999	-0.73	2	2
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.097	0.16	-9999	-0.3	155	155
mol:Pi	-0.022	0.1	-9999	-0.47	2	2
Cone CNG Channel	-0.08	0.14	-9999	-0.44	32	32
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.067	0.22	-9999	-0.73	46	46
RGS9	-0.061	0.16	-9999	-0.44	74	74
PDE6C	0.003	0.005	-9999	-10000	0	0
GNGT2	0.005	0.055	-9999	-0.44	7	7
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.001	0.034	-9999	-0.73	1	1

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.031	0.042	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.099	0.12	-9999	-0.34	45	45
JUN	-0.072	0.14	-9999	-0.37	44	44
HRAS	0.011	0.021	-9999	-0.44	1	1
RET51/GFRalpha1/GDNF/GRB10	-0.1	0.16	-9999	-0.45	45	45
RAP1A	0.012	0	-9999	-10000	0	0
FRS2	0.012	0.001	-9999	-10000	0	0
RAP1A/GDP	0.009	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.1	0.16	-9999	-0.45	45	45
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.012	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.071	0.12	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
RAP1A/GTP	-0.11	0.13	-9999	-0.4	46	46
GRB7	-0.001	0.097	-9999	-0.73	8	8
RET51/GFRalpha1/GDNF	-0.1	0.16	-9999	-0.45	45	45
MAPKKK cascade	-0.11	0.13	-9999	-0.41	45	45
BCAR1	0.011	0.021	-9999	-0.44	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.071	0.12	-9999	-10000	0	0
lamellipodium assembly	-0.097	0.12	-9999	-0.32	45	45
RET51/GFRalpha1/GDNF/SHC	-0.1	0.16	-9999	-0.45	45	45
PIK3CA	0.012	0.001	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.071	0.12	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3	-0.072	0.12	-9999	-0.45	1	1
MAPK3	-0.08	0.14	-9999	-0.38	47	47
DOK1	0.012	0	-9999	-10000	0	0
DOK6	0.001	0.069	-9999	-0.44	11	11
PXN	0.012	0	-9999	-10000	0	0
neurite development	-0.069	0.14	-9999	-0.47	7	7
DOK5	0	0.079	-9999	-0.49	11	11
GFRA1	-0.16	0.22	-9999	-0.44	174	174
MAPK8	-0.082	0.14	-9999	-0.39	44	44
HRAS/GTP	-0.12	0.15	-9999	-0.46	46	46
tube development	-0.061	0.11	-9999	-0.42	1	1
MAPK1	-0.079	0.14	-9999	-0.38	46	46
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.062	0.11	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
SRC	0.012	0	-9999	-10000	0	0
PDLIM7	0.012	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.096	0.16	-9999	-0.44	51	51
SHC1	0.012	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.1	0.16	-9999	-0.45	46	46
RET51/GFRalpha1/GDNF/Dok5	-0.11	0.17	-9999	-0.46	50	50
PRKCA	0.012	0	-9999	-10000	0	0
HRAS/GDP	0.008	0.015	-9999	-0.31	1	1
CREB1	-0.097	0.16	-9999	-0.42	44	44
PIK3R1	0.012	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.062	0.11	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Grb7	-0.11	0.17	-9999	-0.47	52	52
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.062	0.17	-9999	-0.45	74	74
DOK4	0.011	0.021	-9999	-0.44	1	1
JNK cascade	-0.071	0.13	-9999	-0.36	44	44
RET9/GFRalpha1/GDNF/FRS2	-0.071	0.12	-9999	-10000	0	0
SHANK3	0.011	0.021	-9999	-0.44	1	1
RASA1	0.012	0.001	-9999	-10000	0	0
NCK1	0.012	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.063	0.11	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.093	0.15	-9999	-0.42	44	44
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.093	0.15	-9999	-0.42	44	44
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.1	0.18	-9999	-0.53	44	44
PI3K	-0.11	0.2	-9999	-0.49	45	45
SOS1	0.012	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.061	0.11	-9999	-0.42	1	1
GRB10	0.012	0	-9999	-10000	0	0
activation of MAPKK activity	-0.078	0.13	-9999	-0.34	44	44
RET51/GFRalpha1/GDNF/FRS2	-0.1	0.16	-9999	-0.45	45	45
GAB1	0.012	0	-9999	-10000	0	0
IRS1	0.012	0	-9999	-10000	0	0
IRS2	0.012	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.1	0.18	-9999	-0.53	44	44
RET51/GFRalpha1/GDNF/PKC alpha	-0.1	0.16	-9999	-0.45	45	45
GRB2	0.012	0	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
GDNF	0.009	0.006	-9999	-10000	0	0
RAC1	0.012	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.1	0.16	-9999	-0.45	45	45
Rac1/GTP	-0.11	0.14	-9999	-0.38	45	45
RET9/GFRalpha1/GDNF	-0.088	0.13	-9999	-0.26	174	174
GFRalpha1/GDNF	-0.11	0.16	-9999	-0.3	174	174

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.049	0.14	-9999	-0.47	18	18
FZD6	0.012	0	-9999	-10000	0	0
WNT6	-0.025	0.15	-9999	-0.62	26	26
WNT4	-0.009	0.1	-9999	-0.48	20	20
FZD3	0.007	0.06	-9999	-0.73	3	3
WNT5A	0.003	0.08	-9999	-0.68	6	6
WNT11	-0.13	0.29	-9999	-0.7	94	94

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.047	0.14	-10000	0	-0.53	30	30
FYN	-0.014	0.21	-10000	0	-0.66	35	35
LAT/GRAP2/SLP76	-0.047	0.16	-10000	0	-0.56	35	35
IKBKB	0.012	0	-10000	0	-10000	0	0
AKT1	0.007	0.14	-10000	0	-0.44	35	35
B2M	0.012	0.021	-10000	0	-0.44	1	1
IKBKG	-0.016	0.04	-10000	0	-0.17	10	10
MAP3K8	0.012	0	-10000	0	-10000	0	0
mol:Ca2+	-0.02	0.047	-10000	0	-0.15	53	53
integrin-mediated signaling pathway	0.014	0.028	-10000	0	-0.25	5	5
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.009	0.21	-10000	0	-0.64	37	37
TRPV6	-0.085	0.24	-10000	0	-0.73	53	53
CD28	-0.005	0.088	-10000	0	-0.44	18	18
SHC1	-0.011	0.2	-10000	0	-0.65	34	34
receptor internalization	-0.024	0.22	-10000	0	-0.68	38	38
PRF1	-0.019	0.23	-10000	0	-0.83	27	27
KRAS	0.012	0	-10000	0	-10000	0	0
GRB2	0.012	0	-10000	0	-10000	0	0
COT/AKT1	0.015	0.12	-10000	0	-0.36	29	29
LAT	-0.013	0.2	-10000	0	-0.64	36	36
EntrezGene:6955	0.001	0.003	-10000	0	-10000	0	0
CD3D	-0.002	0.082	-10000	0	-0.44	15	15
CD3E	-0.007	0.094	-10000	0	-0.45	20	20
CD3G	-0.026	0.13	-10000	0	-0.44	39	39
RASGRP2	-0.008	0.052	-10000	0	-0.17	37	37
RASGRP1	0.013	0.15	-10000	0	-0.46	31	31
HLA-A	0.012	0.021	-10000	0	-0.44	1	1
RASSF5	0.007	0.047	-10000	0	-0.44	5	5
RAP1A/GTP/RAPL	0.014	0.028	-10000	0	-0.25	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.021	0.05	-10000	0	-0.13	24	24
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.028	0.07	-10000	0	-0.26	22	22
PRKCA	-0.021	0.078	-10000	0	-0.28	25	25
GRAP2	-0.006	0.089	-10000	0	-0.44	19	19
mol:IP3	-0.015	0.15	0.26	50	-0.45	29	79
EntrezGene:6957	0.001	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.023	0.2	-10000	0	-0.63	36	36
ORAI1	0.047	0.11	0.36	52	-10000	0	52
CSK	-0.012	0.2	-10000	0	-0.65	34	34
B7 family/CD28	-0.013	0.21	-10000	0	-0.7	30	30
CHUK	0.012	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.023	0.23	-10000	0	-0.76	34	34
PTPN6	-0.014	0.2	-10000	0	-0.66	34	34
VAV1	-0.019	0.21	-10000	0	-0.66	38	38
Monovalent TCR/CD3	-0.024	0.18	-10000	0	-0.67	25	25
CBL	0.012	0	-10000	0	-10000	0	0
LCK	-0.017	0.21	-10000	0	-0.67	35	35
PAG1	-0.014	0.2	-10000	0	-0.65	35	35
RAP1A	0.012	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.023	0.23	-10000	0	-0.74	35	35
CD80	0.009	0.046	-10000	0	-0.54	3	3
CD86	0.003	0.066	-10000	0	-0.44	10	10
PDK1/CARD11/BCL10/MALT1	-0.035	0.085	-10000	0	-0.29	31	31
HRAS	0.011	0.021	-10000	0	-0.44	1	1
GO:0035030	-0.007	0.17	-10000	0	-0.57	30	30
CD8A	-0.019	0.12	-10000	0	-0.44	33	33
CD8B	-0.001	0.083	-10000	0	-0.46	14	14
PTPRC	-0.024	0.12	-10000	0	-0.44	37	37
PDK1/PKC theta	0.007	0.18	-10000	0	-0.55	33	33
CSK/PAG1	-0.009	0.2	-10000	0	-0.65	32	32
SOS1	0.012	0	-10000	0	-10000	0	0
peptide-MHC class I	0.018	0.022	-10000	0	-0.3	2	2
GRAP2/SLP76	-0.055	0.19	-10000	0	-0.67	34	34
STIM1	0.023	0.058	-10000	0	-10000	0	0
RAS family/GTP	0.029	0.062	-10000	0	-0.18	17	17
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.028	0.24	-10000	0	-0.73	38	38
mol:DAG	-0.028	0.12	-10000	0	-0.4	30	30
RAP1A/GDP	0.011	0.022	-10000	0	-10000	0	0
PLCG1	0.012	0	-10000	0	-10000	0	0
CD247	-0.002	0.081	-10000	0	-0.44	15	15
cytotoxic T cell degranulation	-0.016	0.22	-10000	0	-0.78	27	27
RAP1A/GTP	-0.006	0.017	-10000	0	-0.068	15	15
mol:PI-3-4-5-P3	0	0.17	-10000	0	-0.52	37	37
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.027	0.19	0.28	47	-0.58	30	77
NRAS	0.01	0.03	-10000	0	-0.44	2	2
ZAP70	-0.001	0.08	-10000	0	-0.46	13	13
GRB2/SOS1	0.018	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.049	0.16	-10000	0	-0.57	33	33
MALT1	0.011	0.021	-10000	0	-0.44	1	1
TRAF6	0.012	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.013	0.11	-10000	0	-0.37	39	39
CARD11	-0.024	0.15	-10000	0	-0.58	28	28
PRKCB	-0.041	0.11	-10000	0	-0.33	47	47
PRKCE	-0.021	0.078	-10000	0	-0.28	27	27
PRKCQ	-0.003	0.2	-10000	0	-0.62	36	36
LCP2	0.008	0.042	-10000	0	-0.44	4	4
BCL10	0.011	0.021	-10000	0	-0.44	1	1
regulation of survival gene product expression	0.011	0.12	-10000	0	-0.38	34	34
IKK complex	0.02	0.052	-10000	0	-0.12	21	21
RAS family/GDP	-0.003	0.009	-10000	0	-10000	0	0
MAP3K14	0.021	0.091	-10000	0	-0.28	25	25
PDPK1	0.01	0.14	-10000	0	-0.43	31	31
TCR/CD3/MHC I/CD8/Fyn	-0.026	0.23	-10000	0	-0.77	35	35

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.04	0.11	-10000	0	-0.26	95	95
cell-cell adhesion	0.086	0.15	0.6	4	-10000	0	4
Ephrin B/EPHB2/RasGAP	0.03	0.048	-10000	0	-0.4	4	4
ITSN1	0.011	0.021	-10000	0	-0.44	1	1
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
SHC1	0.012	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.009	0.11	-10000	0	-0.48	24	24
Ephrin B1/EPHB1	-0.11	0.22	-10000	0	-0.48	115	115
HRAS/GDP	-0.087	0.15	-10000	0	-0.54	3	3
Ephrin B/EPHB1/GRB7	-0.086	0.21	-10000	0	-0.42	120	120
Endophilin/SYNJ1	0.025	0.045	-10000	0	-0.38	4	4
KRAS	0.012	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.078	0.19	-10000	0	-0.41	116	116
endothelial cell migration	0.026	0	-10000	0	-10000	0	0
GRB2	0.012	0	-10000	0	-10000	0	0
GRB7	-0.001	0.097	-10000	0	-0.73	8	8
PAK1	0.03	0.046	-10000	0	-10000	0	0
HRAS	0.011	0.021	-10000	0	-0.44	1	1
RRAS	0.025	0.045	-10000	0	-0.38	4	4
DNM1	0.004	0.077	-10000	0	-0.73	5	5
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.077	0.18	-10000	0	-0.39	116	116
lamellipodium assembly	-0.086	0.15	-10000	0	-0.6	4	4
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.032	0.11	-10000	0	-0.4	2	2
PIK3R1	0.012	0	-10000	0	-10000	0	0
EPHB2	0.009	0.049	-10000	0	-0.73	2	2
EPHB3	-0.027	0.17	-10000	0	-0.73	24	24
EPHB1	-0.18	0.32	-10000	0	-0.73	115	115
EPHB4	0.012	0	-10000	0	-10000	0	0
mol:GDP	-0.043	0.15	-10000	0	-0.51	3	3
Ephrin B/EPHB2	0.022	0.048	-10000	0	-0.41	4	4
Ephrin B/EPHB3	0.002	0.1	-10000	0	-0.41	26	26
JNK cascade	-0.077	0.19	-10000	0	-0.4	115	115
Ephrin B/EPHB1	-0.085	0.19	-10000	0	-0.41	116	116
RAP1/GDP	-0.027	0.14	-10000	0	-0.44	3	3
EFNB2	0.012	0	-10000	0	-10000	0	0
EFNB3	0.003	0.07	-10000	0	-0.51	8	8
EFNB1	0.012	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.093	0.2	-10000	0	-0.44	115	115
RAP1B	0.012	0	-10000	0	-10000	0	0
RAP1A	0.012	0	-10000	0	-10000	0	0
CDC42/GTP	-0.089	0.15	-10000	0	-0.62	5	5
Rap1/GTP	-0.086	0.15	-10000	0	-0.61	4	4
axon guidance	-0.04	0.11	-10000	0	-0.26	95	95
MAPK3	-0.018	0.1	-10000	0	-0.36	2	2
MAPK1	-0.017	0.1	-10000	0	-0.36	2	2
Rac1/GDP	-0.033	0.14	-10000	0	-0.46	3	3
actin cytoskeleton reorganization	-0.071	0.12	-10000	0	-0.45	5	5
CDC42/GDP	-0.033	0.14	-10000	0	-0.52	3	3
PI3K	0.029	0	-10000	0	-10000	0	0
EFNA5	-0.079	0.18	-10000	0	-0.44	93	93
Ephrin B2/EPHB4	0.017	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.027	0.037	-10000	0	-10000	0	0
CDC42	0.011	0.021	-10000	0	-0.44	1	1
RAS family/GTP	-0.085	0.14	-10000	0	-0.57	5	5
PTK2	0.022	0.039	-10000	0	-10000	0	0
MAP4K4	-0.077	0.19	-10000	0	-0.4	115	115
SRC	0.012	0	-10000	0	-10000	0	0
KALRN	0.011	0.021	-10000	0	-0.44	1	1
Intersectin/N-WASP	0.018	0.015	-10000	0	-0.3	1	1
neuron projection morphogenesis	-0.022	0.14	-10000	0	-0.44	5	5
MAP2K1	-0.024	0.1	-10000	0	-0.38	2	2
WASL	0.012	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.086	0.2	-10000	0	-0.44	115	115
cell migration	-0.019	0.11	-10000	0	-0.42	2	2
NRAS	0.01	0.03	-10000	0	-0.44	2	2
SYNJ1	0.025	0.045	-10000	0	-0.38	4	4
PXN	0.012	0	-10000	0	-10000	0	0
TF	0.002	0.098	-10000	0	-0.74	2	2
HRAS/GTP	-0.092	0.16	-10000	0	-0.65	4	4
Ephrin B1/EPHB1-2	-0.093	0.2	-10000	0	-0.44	115	115
cell adhesion mediated by integrin	-0.004	0.061	0.38	3	-10000	0	3
RAC1	0.012	0	-10000	0	-10000	0	0
mol:GTP	-0.07	0.18	-10000	0	-0.38	116	116
RAC1-CDC42/GTP	-0.1	0.17	-10000	0	-0.65	13	13
RASA1	0.012	0.001	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.027	0.14	-10000	0	-0.5	3	3
ruffle organization	-0.049	0.17	-10000	0	-0.61	4	4
NCK1	0.012	0	-10000	0	-10000	0	0
receptor internalization	0.025	0.063	-10000	0	-0.41	5	5
Ephrin B/EPHB2/KALRN	0.029	0.049	-10000	0	-0.4	4	4
ROCK1	-0.003	0.1	-10000	0	-0.43	24	24
RAS family/GDP	-0.061	0.1	-10000	0	-0.42	5	5
Rac1/GTP	-0.09	0.16	-10000	0	-0.65	4	4
Ephrin B/EPHB1/Src/Paxillin	-0.035	0.11	-10000	0	-0.44	2	2

×

LPA4-mediated signaling events

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
ADCY4	0.016	0	-9999	-10000	0	0
ADCY5	-0.1	0.13	-9999	-0.25	197	197
ADCY6	0.016	0	-9999	-10000	0	0
ADCY7	0.016	0	-9999	-10000	0	0
ADCY1	0.004	0.072	-9999	-0.42	12	12
ADCY2	-0.008	0.077	-9999	-0.26	39	39
ADCY3	0.016	0	-9999	-10000	0	0
ADCY8	0.002	0.06	-9999	-0.48	7	7
PRKCE	0.01	0	-9999	-10000	0	0
ADCY9	0.015	0.018	-9999	-0.25	2	2
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.014	0.058	-9999	-0.28	2	2

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.058	0.25	-10000	0	-0.88	24	24
NCK1/PAK1/Dok-R	-0.028	0.1	-10000	0	-0.42	24	24
NCK1/Dok-R	0.026	0.28	-10000	0	-1	29	29
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
mol:beta2-estradiol	0.001	0.051	0.26	17	-10000	0	17
RELA	0.012	0	-10000	0	-10000	0	0
SHC1	0.013	0.001	-10000	0	-10000	0	0
Rac/GDP	0.009	0	-10000	0	-10000	0	0
F2	-0.23	0.35	0.25	7	-0.74	147	154
TNIP2	0.012	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.013	0.24	-10000	0	-0.91	29	29
FN1	-0.03	0.16	-10000	0	-0.65	29	29
PLD2	0.027	0.29	-10000	0	-1	29	29
PTPN11	0.012	0	-10000	0	-10000	0	0
GRB14	-0.025	0.14	-10000	0	-0.52	31	31
ELK1	0.037	0.26	-10000	0	-0.91	29	29
GRB7	-0.001	0.097	-10000	0	-0.73	8	8
PAK1	0.012	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.036	0.27	-10000	0	-0.94	32	32
CDKN1A	0.063	0.21	-10000	0	-0.66	18	18
ITGA5	0.007	0.06	-10000	0	-0.73	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.026	0.28	-10000	0	-1	29	29
CRK	0.012	0	-10000	0	-10000	0	0
mol:NO	0.062	0.2	-10000	0	-0.64	26	26
PLG	-0.056	0.32	-10000	0	-1.1	29	29
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.052	0.24	-10000	0	-0.79	29	29
GRB2	0.012	0	-10000	0	-10000	0	0
PIK3R1	0.013	0.001	-10000	0	-10000	0	0
ANGPT2	0.032	0.2	-10000	0	-0.64	6	6
BMX	-0.057	0.31	-10000	0	-1.1	29	29
ANGPT1	0.038	0.25	-10000	0	-1.2	17	17
tube development	0.059	0.22	-10000	0	-0.69	21	21
ANGPT4	-0.001	0.069	-10000	0	-0.73	4	4
response to hypoxia	-0.001	0.017	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	0.004	0.3	-10000	0	-1.1	29	29
alpha5/beta1 Integrin	0.015	0.046	-10000	0	-0.55	3	3
FGF2	-0.019	0.11	-10000	0	-0.44	31	31
STAT5A (dimer)	0.059	0.24	-10000	0	-0.79	21	21
mol:L-citrulline	0.062	0.2	-10000	0	-0.64	26	26
AGTR1	-0.14	0.21	-10000	0	-0.44	156	156
MAPK14	0.03	0.3	-10000	0	-1	29	29
Tie2/SHP2	-0.017	0.22	-10000	0	-1.1	18	18
TEK	-0.021	0.24	-10000	0	-1.2	18	18
RPS6KB1	0.057	0.24	-10000	0	-0.82	27	27
Angiotensin II/AT1	-0.099	0.15	-10000	0	-0.31	156	156
Tie2/Ang1/GRB2	0.023	0.3	-10000	0	-1.1	29	29
MAPK3	0.033	0.26	-10000	0	-0.93	29	29
MAPK1	0.034	0.26	-10000	0	-0.93	29	29
Tie2/Ang1/GRB7	0.016	0.3	-10000	0	-1.1	29	29
NFKB1	0.012	0	-10000	0	-10000	0	0
MAPK8	0.027	0.29	-10000	0	-1	29	29
PI3K	0.046	0.28	-10000	0	-0.98	27	27
FES	0.029	0.3	-10000	0	-1	29	29
Crk/Dok-R	0.026	0.28	-10000	0	-1	29	29
Tie2/Ang1/ABIN2	0.023	0.3	-10000	0	-1.1	29	29
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.062	0.23	-10000	0	-0.76	26	26
STAT5A	0.013	0	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.057	0.24	-10000	0	-0.82	27	27
Tie2/Ang2	0.045	0.28	-10000	0	-0.96	21	21
Tie2/Ang1	0.021	0.32	-10000	0	-1.1	29	29
FOXO1	0.065	0.23	-10000	0	-0.78	24	24
ELF1	0.017	0.021	-10000	0	-10000	0	0
ELF2	0.025	0.29	-10000	0	-1	29	29
mol:Choline	0.029	0.27	-10000	0	-0.97	29	29
cell migration	-0.021	0.06	-10000	0	-0.25	10	10
FYN	0.055	0.24	-10000	0	-0.8	21	21
DOK2	0.001	0.072	-10000	0	-0.44	12	12
negative regulation of cell cycle	0.065	0.2	-10000	0	-0.59	18	18
ETS1	0.01	0.056	-10000	0	-0.31	8	8
PXN	0.066	0.21	-10000	0	-0.69	24	24
ITGB1	0.012	0	-10000	0	-10000	0	0
NOS3	0.058	0.22	-10000	0	-0.74	26	26
RAC1	0.012	0	-10000	0	-10000	0	0
TNF	0.01	0.058	-10000	0	-0.44	2	2
MAPKKK cascade	0.029	0.27	-10000	0	-0.97	29	29
RASA1	0.012	0.001	-10000	0	-10000	0	0
Tie2/Ang1/Shc	0.024	0.3	-10000	0	-1.1	29	29
NCK1	0.012	0	-10000	0	-10000	0	0
vasculogenesis	0.064	0.19	-10000	0	-0.57	26	26
mol:Phosphatidic acid	0.029	0.27	-10000	0	-0.97	29	29
mol:Angiotensin II	0.001	0.003	-10000	0	-10000	0	0
mol:NADP	0.062	0.2	-10000	0	-0.64	26	26
Rac1/GTP	-0.043	0.19	-10000	0	-0.76	27	27
MMP2	0.023	0.29	-10000	0	-1	29	29

×

Signaling events mediated by PRL

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
CCNE1	0.007	0.06	-10000	0	-0.73	3	3
mol:Halofuginone	0.005	0	-10000	0	-10000	0	0
ITGA1	0.012	0	-10000	0	-10000	0	0
CDKN1A	0.027	0.027	-10000	0	-0.36	2	2
PRL-3/alpha Tubulin	-0.078	0.21	-10000	0	-0.55	77	77
mol:Ca2+	-0.022	0.22	0.32	61	-0.54	56	117
AGT	-0.079	0.24	-10000	0	-0.73	56	56
CCNA2	0.034	0.01	-10000	0	-10000	0	0
TUBA1B	0.012	0	-10000	0	-10000	0	0
EGR1	0.02	0.015	-10000	0	-0.3	1	1
CDK2/Cyclin E1	0.034	0.041	-10000	0	-0.36	5	5
MAPK3	-0.078	0.21	-10000	0	-0.55	78	78
PRL-2 /Rab GGTase beta	0.018	0	-10000	0	-10000	0	0
MAPK1	-0.077	0.21	-10000	0	-0.55	77	77
PTP4A1	0.03	0.011	-10000	0	-10000	0	0
PTP4A3	-0.11	0.28	-10000	0	-0.73	77	77
PTP4A2	0.012	0	-10000	0	-10000	0	0
ITGB1	-0.077	0.21	-10000	0	-0.55	77	77
SRC	0.012	0	-10000	0	-10000	0	0
RAC1	-0.006	0.077	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.018	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.034	0.01	-10000	0	-10000	0	0
RABGGTA	0.012	0	-10000	0	-10000	0	0
BCAR1	0.054	0.12	0.32	77	-0.32	1	78
RHOC	-0.006	0.077	-10000	0	-10000	0	0
RHOA	-0.006	0.077	-10000	0	-10000	0	0
cell motility	-0.003	0.08	-10000	0	-0.38	1	1
PRL-1/alpha Tubulin	0.034	0.01	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.078	0.21	-10000	0	-0.55	77	77
ROCK1	-0.003	0.08	-10000	0	-0.38	1	1
RABGGTB	0.012	0	-10000	0	-10000	0	0
CDK2	0.012	0	-10000	0	-10000	0	0
mitosis	0.03	0.011	-10000	0	-10000	0	0
ATF5	0.012	0	-10000	0	-10000	0	0

×

IL12-mediated 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
IL12/IL12R/TYK2/JAK2/SOCS1	0.001	0.12	-10000	0	-0.36	23	23
TBX21	-0.12	0.44	-10000	0	-1.2	52	52
B2M	0.011	0.022	-10000	0	-0.44	1	1
TYK2	0.013	0.022	-10000	0	-10000	0	0
IL12RB1	-0.006	0.1	-10000	0	-0.48	19	19
GADD45B	-0.047	0.3	-10000	0	-0.89	29	29
IL12RB2	0.004	0.077	-10000	0	-0.53	8	8
GADD45G	-0.051	0.31	-10000	0	-0.97	24	24
natural killer cell activation	0	0.023	-10000	0	-10000	0	0
RELB	0.012	0	-10000	0	-10000	0	0
RELA	0.012	0	-10000	0	-10000	0	0
IL18	0.014	0.03	-10000	0	-0.43	2	2
IL2RA	0.002	0.069	-10000	0	-0.44	11	11
IFNG	-0.066	0.22	-10000	0	-0.73	47	47
STAT3 (dimer)	-0.049	0.3	-10000	0	-0.79	38	38
HLA-DRB5	-0.03	0.16	-10000	0	-0.6	32	32
FASLG	-0.12	0.44	-10000	0	-1.1	55	55
NF kappa B2 p52/RelB	-0.17	0.3	-10000	0	-0.9	51	51
CD4	-0.004	0.085	-10000	0	-0.44	17	17
SOCS1	-0.006	0.11	-10000	0	-0.73	11	11
EntrezGene:6955	0	0.01	-10000	0	-10000	0	0
CD3D	-0.002	0.081	-10000	0	-0.44	15	15
CD3E	-0.007	0.093	-10000	0	-0.44	20	20
CD3G	-0.026	0.13	-10000	0	-0.44	39	39
IL12Rbeta2/JAK2	0.014	0.073	-10000	0	-0.39	10	10
CCL3	-0.1	0.38	-10000	0	-0.99	47	47
CCL4	-0.091	0.37	-10000	0	-0.95	52	52
HLA-A	0.011	0.022	-10000	0	-0.44	1	1
IL18/IL18R	0.03	0.089	-10000	0	-0.46	1	1
NOS2	-0.11	0.42	-10000	0	-1.2	43	43
IL12/IL12R/TYK2/JAK2/SPHK2	0.007	0.11	-10000	0	-0.35	18	18
IL1R1	-0.094	0.38	-10000	0	-0.98	51	51
IL4	0.002	0.023	-10000	0	-10000	0	0
JAK2	0.01	0.045	-10000	0	-0.47	3	3
EntrezGene:6957	0	0.01	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.06	0.31	-10000	0	-0.9	44	44
RAB7A	-0.02	0.26	-10000	0	-0.79	21	21
lysosomal transport	-0.017	0.25	-10000	0	-0.74	21	21
FOS	-0.047	0.29	-10000	0	-1	28	28
STAT4 (dimer)	-0.052	0.34	-10000	0	-0.9	39	39
STAT5A (dimer)	-0.2	0.33	-10000	0	-0.89	66	66
GZMA	-0.14	0.48	-10000	0	-1.2	62	62
GZMB	-0.15	0.41	-10000	0	-0.96	63	63
HLX	0.011	0.021	-10000	0	-0.44	1	1
LCK	-0.1	0.39	-10000	0	-0.99	52	52
TCR/CD3/MHC II/CD4	-0.037	0.22	-10000	0	-0.64	38	38
IL2/IL2R	0.012	0.071	-10000	0	-0.48	6	6
MAPK14	-0.042	0.31	-10000	0	-0.9	30	30
CCR5	-0.057	0.33	-10000	0	-1.1	24	24
IL1B	-0.066	0.23	-10000	0	-0.72	50	50
STAT6	-0.004	0.11	-10000	0	-10000	0	0
STAT4	-0.011	0.1	-10000	0	-0.44	24	24
STAT3	0.012	0	-10000	0	-10000	0	0
STAT1	0.011	0.035	-10000	0	-0.73	1	1
NFKB1	0.012	0	-10000	0	-10000	0	0
NFKB2	0.012	0	-10000	0	-10000	0	0
IL12B	0.002	0.073	-10000	0	-0.73	4	4
CD8A	-0.021	0.12	-10000	0	-0.44	33	33
CD8B	-0.003	0.083	-10000	0	-0.46	14	14
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.002	0.12	0.36	23	-10000	0	23
IL2RB	0	0.075	-10000	0	-0.44	13	13
proteasomal ubiquitin-dependent protein catabolic process	-0.042	0.31	-10000	0	-0.81	39	39
IL2RG	0.01	0.03	-10000	0	-0.44	2	2
IL12	0.009	0.078	-10000	0	-0.46	9	9
STAT5A	0.012	0	-10000	0	-10000	0	0
CD247	-0.002	0.081	-10000	0	-0.44	15	15
IL2	0.003	0.005	-10000	0	-10000	0	0
SPHK2	0.011	0.021	-10000	0	-0.44	1	1
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.006	0.064	-10000	0	-0.5	6	6
IL12/IL12R/TYK2/JAK2	-0.11	0.42	-10000	0	-1	59	59
MAP2K3	-0.046	0.31	-10000	0	-0.91	30	30
RIPK2	0.012	0	-10000	0	-10000	0	0
MAP2K6	-0.048	0.31	-10000	0	-0.91	30	30
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0	0.075	-10000	0	-0.44	13	13
IL18RAP	-0.009	0.11	-10000	0	-0.45	24	24
IL12Rbeta1/TYK2	0.005	0.081	-10000	0	-0.35	19	19
EOMES	-0.054	0.28	-10000	0	-1.1	27	27
STAT1 (dimer)	-0.068	0.31	-10000	0	-0.76	46	46
T cell proliferation	-0.028	0.26	-10000	0	-0.65	38	38
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.007	0.064	-10000	0	-0.44	9	9
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.12	0.21	-10000	0	-0.73	31	31
ATF2	-0.031	0.29	-10000	0	-0.85	26	26

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.004	0.089	-10000	0	-0.42	7	7
ER alpha/Gai/GDP/Gbeta gamma	-0.093	0.24	-10000	0	-0.7	44	44
AKT1	-0.056	0.25	-10000	0	-0.83	42	42
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.061	0.26	-10000	0	-0.85	42	42
mol:Ca2+	0.02	0.062	-10000	0	-0.42	5	5
IGF1R	0.012	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.008	0.078	-10000	0	-0.25	42	42
SHC1	0.012	0	-10000	0	-10000	0	0
apoptosis	0.052	0.24	0.78	42	-10000	0	42
RhoA/GTP	-0.017	0.05	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.092	0.18	-10000	0	-0.61	36	36
regulation of stress fiber formation	-0.023	0.055	-10000	0	-10000	0	0
E2/ERA-ERB (dimer)	-0.011	0.082	-10000	0	-0.26	45	45
KRAS	0.012	0	-10000	0	-10000	0	0
G13/GTP	-0.007	0.07	-10000	0	-0.23	42	42
pseudopodium formation	0.023	0.055	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1	-0.008	0.078	-10000	0	-0.25	42	42
GRB2	0.012	0	-10000	0	-10000	0	0
GNG2	-0.006	0.089	-10000	0	-0.44	19	19
GNAO1	-0.11	0.2	-10000	0	-0.44	125	125
HRAS	0.011	0.021	-10000	0	-0.44	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.057	0.2	-10000	0	-0.6	48	48
E2/ER beta (dimer)	0.006	0.03	-10000	0	-0.31	4	4
mol:GDP	-0.032	0.096	-10000	0	-0.32	42	42
mol:NADP	-0.057	0.2	-10000	0	-0.6	48	48
PIK3R1	0.012	0	-10000	0	-10000	0	0
mol:IP3	0.02	0.064	-10000	0	-0.44	5	5
IGF-1R heterotetramer	0.012	0	-10000	0	-10000	0	0
PLCB1	0.015	0.066	-10000	0	-0.44	6	6
PLCB2	0.018	0.057	-10000	0	-0.47	3	3
IGF1	-0.1	0.19	-10000	0	-0.44	114	114
mol:L-citrulline	-0.057	0.2	-10000	0	-0.6	48	48
RHOA	0.012	0	-10000	0	-10000	0	0
Gai/GDP	-0.16	0.32	-10000	0	-0.67	125	125
JNK cascade	0.006	0.03	-10000	0	-0.31	4	4
BCAR1	0.011	0.021	-10000	0	-0.44	1	1
ESR2	0.008	0.042	-10000	0	-0.44	4	4
GNAQ	0.01	0.03	-10000	0	-0.44	2	2
ESR1	-0.029	0.13	-10000	0	-0.44	42	42
Gq family/GDP/Gbeta gamma	0.018	0.068	-10000	0	-0.47	3	3
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.003	0.083	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.092	0.18	-10000	0	-0.63	34	34
GNAZ	0.007	0.047	-10000	0	-0.44	5	5
E2/ER alpha (dimer)	-0.02	0.092	-10000	0	-0.31	42	42
STRN	0.012	0.001	-10000	0	-10000	0	0
GNAL	-0.014	0.11	-10000	0	-0.44	27	27
PELP1	0.012	0	-10000	0	-10000	0	0
MAPK11	0.011	0.041	-10000	0	-0.33	6	6
GNAI2	0.012	0	-10000	0	-10000	0	0
GNAI3	0.012	0	-10000	0	-10000	0	0
GNAI1	-0.001	0.077	-10000	0	-0.44	14	14
HBEGF	-0.086	0.21	-10000	0	-0.59	47	47
cAMP biosynthetic process	-0.031	0.082	-10000	0	-0.4	9	9
SRC	-0.082	0.22	-10000	0	-0.66	44	44
PI3K	0.018	0	-10000	0	-10000	0	0
GNB1	0.012	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.034	0.093	-10000	0	-0.46	7	7
SOS1	0.012	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.11	0.17	-10000	0	-0.54	46	46
Gs family/GTP	-0.017	0.089	-10000	0	-0.41	9	9
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.022	0.02	-10000	0	-10000	0	0
vasodilation	-0.053	0.19	-10000	0	-0.56	48	48
mol:DAG	0.02	0.064	-10000	0	-0.44	5	5
Gs family/GDP/Gbeta gamma	-0.042	0.1	-10000	0	-0.44	15	15
MSN	0.024	0.058	-10000	0	-10000	0	0
Gq family/GTP	0.012	0.059	-10000	0	-0.5	3	3
mol:PI-3-4-5-P3	-0.057	0.24	-10000	0	-0.81	42	42
NRAS	0.01	0.03	-10000	0	-0.44	2	2
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.053	0.19	0.56	48	-10000	0	48
GRB2/SOS1	0.018	0	-10000	0	-10000	0	0
RhoA/GDP	-0.03	0.09	-10000	0	-0.3	42	42
NOS3	-0.061	0.22	-10000	0	-0.63	48	48
GNA11	0.01	0.03	-10000	0	-0.44	2	2
MAPKKK cascade	-0.042	0.2	-10000	0	-0.64	42	42
E2/ER alpha (dimer)/PELP1/Src	-0.097	0.19	-10000	0	-0.57	47	47
ruffle organization	0.023	0.055	-10000	0	-10000	0	0
ROCK2	0.019	0.062	-10000	0	-10000	0	0
GNA14	0.01	0.03	-10000	0	-0.44	2	2
GNA15	0.004	0.077	-10000	0	-0.73	5	5
GNA13	0.012	0	-10000	0	-10000	0	0
MMP9	-0.1	0.22	-10000	0	-0.49	82	82
MMP2	-0.075	0.21	-10000	0	-0.6	47	47

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.018	0.11	-9999	-0.48	10	10
NF kappa B1 p50/RelA/I kappa B alpha	-0.011	0.072	-9999	-10000	0	0
AP1	-0.048	0.095	-9999	-0.38	14	14
mol:PIP3	-0.04	0.081	-9999	-10000	0	0
AKT1	0.021	0.08	-9999	-0.43	1	1
PTK2B	-0.009	0.077	-9999	-0.28	10	10
RHOA	0.018	0.033	-9999	-10000	0	0
PIK3CB	0.012	0.001	-9999	-10000	0	0
mol:Ca2+	0.011	0.067	-9999	-0.33	1	1
MAGI3	0.011	0.021	-9999	-0.44	1	1
RELA	0.012	0	-9999	-10000	0	0
apoptosis	-0.036	0.12	-9999	-0.42	13	13
HRAS/GDP	0.008	0.015	-9999	-0.31	1	1
positive regulation of microtubule depolymerization	-0.04	0.12	-9999	-0.35	27	27
NF kappa B1 p50/RelA	-0.041	0.083	-9999	-0.42	3	3
endothelial cell migration	-0.023	0.12	-9999	-0.65	6	6
ADCY4	-0.072	0.19	-9999	-0.48	67	67
ADCY5	-0.16	0.26	-9999	-0.53	126	126
ADCY6	-0.072	0.19	-9999	-0.48	67	67
ADCY7	-0.072	0.19	-9999	-0.48	67	67
ADCY1	-0.077	0.19	-9999	-0.48	70	70
ADCY2	-0.092	0.22	-9999	-0.51	82	82
ADCY3	-0.072	0.19	-9999	-0.48	67	67
ADCY8	-0.078	0.19	-9999	-0.49	67	67
ADCY9	-0.073	0.19	-9999	-0.48	69	69
GSK3B	-0.003	0.073	-9999	-0.34	2	2
arachidonic acid secretion	-0.078	0.2	-9999	-0.57	48	48
GNG2	-0.006	0.089	-9999	-0.44	19	19
TRIP6	0.02	0.021	-9999	-0.27	2	2
GNAO1	-0.089	0.17	-9999	-0.49	45	45
HRAS	0.011	0.021	-9999	-0.44	1	1
NFKBIA	0	0.085	-9999	-10000	0	0
GAB1	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.061	0.26	-9999	-0.88	43	43
JUN	0.012	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	0.015	0.028	-9999	-0.48	1	1
TIAM1	-0.095	0.3	-9999	-1	43	43
PIK3R1	0.012	0.001	-9999	-10000	0	0
mol:IP3	0.011	0.068	-9999	-0.34	1	1
PLCB3	0.02	0.025	-9999	-0.43	1	1
FOS	0.005	0.055	-9999	-0.44	7	7
positive regulation of mitosis	-0.078	0.2	-9999	-0.57	48	48
LPA/LPA1-2-3	-0.036	0.12	-9999	-0.43	14	14
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	-0.001	0.001	-9999	-10000	0	0
BCAR1	0.011	0.021	-9999	-0.44	1	1
stress fiber formation	-0.011	0.09	-9999	-0.32	9	9
GNAZ	-0.022	0.1	-9999	-0.48	4	4
EGFR/PI3K-beta/Gab1	-0.041	0.083	-9999	-10000	0	0
positive regulation of dendritic cell cytokine production	-0.044	0.11	-9999	-0.43	14	14
LPA/LPA2/MAGI-3	0.016	0.028	-9999	-0.47	1	1
ARHGEF1	-0.004	0.084	-9999	-0.39	2	2
GNAI2	-0.019	0.099	-9999	-0.47	2	2
GNAI3	-0.019	0.099	-9999	-0.47	2	2
GNAI1	-0.026	0.12	-9999	-0.5	11	11
LPA/LPA3	-0.019	0.096	-9999	-0.34	35	35
LPA/LPA2	0.008	0.029	-9999	-0.55	1	1
LPA/LPA1	-0.033	0.12	-9999	-0.3	70	70
HB-EGF/EGFR	-0.032	0.14	-9999	-0.48	39	39
HBEGF	-0.033	0.16	-9999	-0.54	42	42
mol:DAG	0.011	0.068	-9999	-0.34	1	1
cAMP biosynthetic process	-0.096	0.21	-9999	-0.55	59	59
NFKB1	0.012	0	-9999	-10000	0	0
SRC	0.012	0	-9999	-10000	0	0
GNB1	0.012	0.001	-9999	-10000	0	0
LYN	0	0.085	-9999	-10000	0	0
GNAQ	-0.004	0.073	-9999	-0.32	7	7
LPAR2	0.01	0.035	-9999	-0.73	1	1
LPAR3	-0.028	0.13	-9999	-0.48	35	35
LPAR1	-0.051	0.16	-9999	-0.43	66	66
IL8	-0.21	0.18	-9999	-0.44	67	67
PTK2	-0.027	0.11	-9999	-0.4	14	14
Rac1/GDP	0.009	0	-9999	-10000	0	0
CASP3	-0.036	0.12	-9999	-0.42	13	13
EGFR	0.01	0.021	-9999	-0.44	1	1
PLCG1	0.001	0.077	-9999	-0.3	7	7
PLD2	-0.027	0.11	-9999	-0.4	14	14
G12/G13	-0.008	0.091	-9999	-0.42	2	2
PI3K-beta	-0.027	0.068	-9999	-0.46	2	2
cell migration	-0.011	0.094	-9999	-0.26	43	43
SLC9A3R2	0.011	0.021	-9999	-0.44	1	1
PXN	-0.012	0.091	-9999	-0.33	9	9
HRAS/GTP	-0.081	0.2	-9999	-0.59	48	48
RAC1	0.012	0	-9999	-10000	0	0
MMP9	-0.052	0.2	-9999	-0.71	40	40
PRKCE	0.012	0.001	-9999	-10000	0	0
PRKCD	0.015	0.065	-9999	-10000	0	0
Gi(beta/gamma)	-0.072	0.2	-9999	-0.55	48	48
mol:LPA	0.001	0.018	-9999	-0.19	3	3
TRIP6/p130 Cas/FAK1/Paxillin	-0.009	0.11	-9999	-0.4	8	8
MAPKKK cascade	-0.078	0.2	-9999	-0.57	48	48
contractile ring contraction involved in cytokinesis	0.018	0.033	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.004	0.073	-9999	-0.31	8	8
GNA15	-0.007	0.08	-9999	-0.33	11	11
GNA12	0.012	0	-9999	-10000	0	0
GNA13	0.012	0	-9999	-10000	0	0
MAPT	-0.042	0.12	-9999	-0.36	27	27
GNA11	-0.004	0.073	-9999	-0.32	6	6
Rac1/GTP	-0.066	0.28	-9999	-0.93	43	43
MMP2	-0.023	0.12	-9999	-0.65	6	6

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.011	0.021	-9999	-0.44	1	1
EGFR	0.011	0.021	-9999	-0.44	1	1
EGF/EGFR	-0.052	0.15	-9999	-0.46	39	39
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.018	0.11	-9999	-0.4	17	17
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.03	0.17	-9999	-0.73	26	26
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.089	0.21	-9999	-0.49	91	91
EGF/EGFR dimer/SHC	-0.039	0.13	-9999	-0.47	17	17
mol:GDP	-0.021	0.11	-9999	-0.4	17	17
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.01	0.03	-9999	-0.44	2	2
GRB2/SOS1	0.018	0	-9999	-10000	0	0
HRAS/GTP	-0.042	0.09	-9999	-0.36	17	17
SHC1	0.012	0	-9999	-10000	0	0
HRAS/GDP	-0.043	0.092	-9999	-0.37	17	17
FRAP1	-0.022	0.11	-9999	-0.38	17	17
EGF/EGFR dimer	-0.056	0.15	-9999	-0.35	92	92
SOS1	0.012	0	-9999	-10000	0	0
GRB2	0.012	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.015	0.13	-9999	-0.53	28	28

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.012	0	-9999	-10000	0	0
ITGB7	-0.006	0.089	-9999	-0.44	19	19
ITGA4	-0.005	0.087	-9999	-0.44	18	18
alpha4/beta7 Integrin	-0.007	0.094	-9999	-0.33	33	33
alpha4/beta1 Integrin	0.006	0.062	-9999	-0.3	18	18

×

Nectin adhesion pathway

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
PDGFRB	0.004	0.077	-9999	-0.73	5	5
alphaV beta3 Integrin	0.015	0.033	-9999	-0.3	5	5
PTK2	0.029	0.061	-9999	-10000	0	0
positive regulation of JNK cascade	-0.008	0.044	-9999	-0.26	13	13
CDC42/GDP	0.038	0.071	-9999	-0.35	13	13
Rac1/GDP	0.04	0.07	-9999	-0.34	13	13
RAP1B	0.012	0	-9999	-10000	0	0
RAP1A	0.012	0	-9999	-10000	0	0
CTNNB1	0.012	0	-9999	-10000	0	0
CDC42/GTP	-0.01	0.054	-9999	-0.32	13	13
nectin-3/I-afadin	0.009	0.053	-9999	-0.3	13	13
RAPGEF1	0.035	0.073	-9999	-0.38	13	13
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.031	0.08	-9999	-0.43	13	13
PDGFB-D/PDGFRB	0.004	0.077	-9999	-0.73	5	5
TLN1	0.022	0.028	-9999	-10000	0	0
Rap1/GTP	-0.008	0.046	-9999	-10000	0	0
IQGAP1	0.012	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.023	0.011	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.009	0.053	-9999	-0.3	13	13
PVR	0.012	0	-9999	-10000	0	0
Necl-5(dimer)	0.012	0	-9999	-10000	0	0
mol:GDP	0.036	0.083	-9999	-0.42	13	13
MLLT4	0.011	0.021	-9999	-0.44	1	1
PIK3CA	0.012	0.001	-9999	-10000	0	0
PI3K	0.025	0.059	-9999	-0.4	5	5
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.018	0.015	-9999	-0.3	1	1
positive regulation of lamellipodium assembly	-0.013	0.055	-9999	-0.28	15	15
PVRL1	0.012	0	-9999	-10000	0	0
PVRL3	0	0.072	-9999	-0.44	12	12
PVRL2	0.012	0	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
CDH1	0.012	0	-9999	-10000	0	0
CLDN1	-0.67	0.21	-9999	-0.73	418	418
JAM-A/CLDN1	-0.4	0.14	-9999	-0.44	418	418
SRC	0.026	0.087	-9999	-0.48	13	13
ITGB3	0.007	0.047	-9999	-0.44	5	5
nectin-1(dimer)/I-afadin/I-afadin	0.018	0.015	-9999	-0.3	1	1
FARP2	0.034	0.078	-9999	-0.42	13	13
RAC1	0.012	0	-9999	-10000	0	0
CTNNA1	0.012	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.017	0.045	-9999	-10000	0	0
nectin-1/I-afadin	0.018	0.015	-9999	-0.3	1	1
nectin-2/I-afadin	0.018	0.015	-9999	-0.3	1	1
RAC1/GTP/IQGAP1/filamentous actin	0.017	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.017	0.045	-9999	-10000	0	0
CDC42/GTP/IQGAP1/filamentous actin	0.016	0.013	-9999	-0.25	1	1
F11R	0.012	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.008	0.044	-9999	-0.26	13	13
alphaV/beta3 Integrin/Talin	0.032	0.034	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.018	0.015	-9999	-0.3	1	1
nectin-2(dimer)/I-afadin/I-afadin	0.018	0.015	-9999	-0.3	1	1
PIP5K1C	0.017	0.03	-9999	-0.22	1	1
VAV2	0.025	0.1	-9999	-0.42	22	22
RAP1/GDP	-0.01	0.055	-9999	-0.32	13	13
ITGAV	0.012	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.017	0.045	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin	0.009	0.053	-9999	-0.3	13	13
Rac1/GTP	-0.015	0.066	-9999	-0.33	15	15
PTPRM	0.012	0.031	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	0.036	0.01	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.011	0.021	-9999	-0.44	1	1

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.017	0.038	-9999	-0.55	1	1
VDR	0.012	0	-9999	-10000	0	0
FAM120B	0.012	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.041	0.12	-9999	-0.47	2	2
RXRs/LXRs/DNA/Oxysterols	-0.025	0.11	-9999	-0.4	8	8
MED1	0.011	0.035	-9999	-0.73	1	1
mol:9cRA	0.005	0.007	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.038	0.11	-9999	-0.42	2	2
RXRs/NUR77	-0.063	0.14	-9999	-0.53	8	8
RXRs/PPAR	-0.054	0.12	-9999	-0.45	3	3
NCOR2	0.011	0.021	-9999	-0.44	1	1
VDR/VDR/Vit D3	0.009	0	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	0.026	0.031	-9999	-0.41	1	1
RARA	0.01	0.041	-9999	-0.58	2	2
NCOA1	0.012	0	-9999	-10000	0	0
VDR/VDR/DNA	0.012	0	-9999	-10000	0	0
RARs/RARs/DNA/9cRA	0.021	0.031	-9999	-0.41	1	1
RARG	0.012	0	-9999	-10000	0	0
RPS6KB1	0.027	0.043	-9999	-0.41	1	1
RARs/THRs/DNA/SMRT	-0.038	0.11	-9999	-0.42	3	3
THRA	0.011	0.035	-9999	-0.73	1	1
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0.009	0	-9999	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.058	0.12	-9999	-0.33	1	1
NR1H4	-0.24	0.22	-9999	-0.44	250	250
RXRs/LXRs/DNA	-0.035	0.12	-9999	-0.4	1	1
NR1H2	0.016	0.022	-9999	-0.43	1	1
NR1H3	0.017	0.006	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.052	0.11	-9999	-10000	0	0
NR4A1	0	0.093	-9999	-0.69	8	8
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.17	0.15	-9999	-0.39	111	111
RXRG	-0.16	0.22	-9999	-0.43	175	175
RXR alpha/CCPG	0.021	0.015	-9999	-0.3	1	1
RXRA	0.016	0.022	-9999	-0.43	1	1
RXRB	0.017	0.006	-9999	-10000	0	0
THRB	-0.12	0.2	-9999	-0.44	131	131
PPARG	0.009	0.036	-9999	-0.44	3	3
PPARD	0.011	0.021	-9999	-0.44	1	1
TNF	-0.018	0.12	-9999	-0.81	3	3
mol:Oxysterols	0.005	0.006	-9999	-10000	0	0
cholesterol transport	-0.025	0.11	-9999	-0.39	8	8
PPARA	0.012	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.008	0.042	-9999	-0.44	4	4
RXRs/NUR77/BCL2	-0.077	0.13	-9999	-0.49	12	12
SREBF1	-0.016	0.1	-9999	-0.51	1	1
RXRs/RXRs/DNA/9cRA	-0.058	0.12	-9999	-0.33	1	1
ABCA1	-0.022	0.14	-9999	-0.98	5	5
RARs/THRs	-0.034	0.11	-9999	-0.41	4	4
RXRs/FXR	-0.19	0.17	-9999	-0.43	108	108
BCL2	-0.009	0.096	-9999	-0.44	22	22

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.017	0.078	-10000	0	-0.62	7	7
oxygen homeostasis	-0.012	0.013	-10000	0	-10000	0	0
TCEB2	0.011	0.035	-10000	0	-0.73	1	1
TCEB1	0.012	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.033	0.058	-10000	0	-0.4	1	1
EPO	-0.14	0.2	-10000	0	-0.7	10	10
FIH (dimer)	0.003	0.011	-10000	0	-10000	0	0
APEX1	-0.002	0.014	-10000	0	-10000	0	0
SERPINE1	-0.22	0.34	-10000	0	-0.82	92	92
FLT1	-0.006	0.041	-10000	0	-0.7	1	1
ADORA2A	-0.15	0.22	-10000	0	-0.66	37	37
germ cell development	-0.15	0.22	-10000	0	-0.66	40	40
SLC11A2	-0.15	0.23	-10000	0	-0.68	37	37
BHLHE40	-0.16	0.23	-10000	0	-0.7	39	39
HIF1AN	0.003	0.011	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.072	0.12	-10000	0	-10000	0	0
ETS1	0.025	0.021	-10000	0	-0.43	1	1
CITED2	-0.008	0.023	-10000	0	-10000	0	0
KDR	-0.008	0.066	-10000	0	-0.91	2	2
PGK1	-0.15	0.22	-10000	0	-0.68	37	37
SIRT1	0.012	0.001	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.18	0.26	-10000	0	-0.81	38	38
EPAS1	-0.045	0.081	-10000	0	-0.36	1	1
SP1	0.019	0.002	-10000	0	-10000	0	0
ABCG2	-0.38	0.28	-10000	0	-0.73	115	115
EFNA1	-0.15	0.22	-10000	0	-0.68	37	37
FXN	-0.15	0.22	-10000	0	-0.66	38	38
POU5F1	-0.16	0.23	-10000	0	-0.7	40	40
neuron apoptosis	0.17	0.26	0.78	38	-10000	0	38
EP300	0.012	0	-10000	0	-10000	0	0
EGLN3	-0.003	0.052	-10000	0	-0.44	6	6
EGLN2	0.002	0.024	-10000	0	-0.44	1	1
EGLN1	0.003	0.011	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.024	0.023	-10000	0	-0.47	1	1
VHL	0.012	0	-10000	0	-10000	0	0
ARNT	-0.003	0.026	-10000	0	-0.46	1	1
SLC2A1	-0.16	0.24	-10000	0	-0.7	49	49
TWIST1	-0.17	0.28	-10000	0	-0.84	47	47
ELK1	0.019	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.068	0.12	-10000	0	-10000	0	0
VEGFA	-0.15	0.23	-10000	0	-0.68	38	38
CREBBP	0.012	0	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.026	0.19	-9999	-0.61	34	34
MKNK1	0.012	0	-9999	-10000	0	0
MAPK14	-0.007	0.091	-9999	-0.36	2	2
ATF2/c-Jun	0.011	0.073	-9999	-0.49	1	1
MAPK11	-0.01	0.11	-9999	-0.64	4	4
MITF	-0.007	0.12	-9999	-0.36	31	31
MAPKAPK5	-0.001	0.11	-9999	-0.34	30	30
KRT8	-0.001	0.11	-9999	-0.34	30	30
MAPKAPK3	0.012	0	-9999	-10000	0	0
MAPKAPK2	0.012	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.012	0.14	-9999	-0.43	31	31
CEBPB	-0.001	0.11	-9999	-0.52	3	3
SLC9A1	-0.002	0.12	-9999	-0.36	31	31
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.004	0.11	-9999	-0.5	3	3
p38alpha-beta/MNK1	0.002	0.12	-9999	-0.58	4	4
JUN	0.011	0.073	-9999	-0.48	1	1
PPARGC1A	-0.04	0.16	-9999	-0.43	35	35
USF1	-0.001	0.11	-9999	-0.34	30	30
RAB5/GDP/GDI1	0.002	0.08	-9999	-0.39	3	3
NOS2	-0.04	0.25	-9999	-0.88	33	33
DDIT3	-0.002	0.12	-9999	-0.34	30	30
RAB5A	0.011	0.021	-9999	-0.44	1	1
HSPB1	0.006	0.092	-9999	-0.42	4	4
p38alpha-beta/HBP1	0.002	0.12	-9999	-0.58	4	4
CREB1	0.001	0.12	-9999	-0.36	30	30
RAB5/GDP	0.008	0.015	-9999	-0.31	1	1
EIF4E	0.003	0.1	-9999	-0.52	4	4
RPS6KA4	-0.001	0.11	-9999	-0.34	30	30
PLA2G4A	-0.024	0.13	-9999	-0.5	10	10
GDI1	-0.001	0.11	-9999	-0.34	30	30
TP53	-0.007	0.14	-9999	-0.42	31	31
RPS6KA5	-0.002	0.12	-9999	-0.35	30	30
ESR1	-0.03	0.15	-9999	-0.43	31	31
HBP1	0.012	0	-9999	-10000	0	0
MEF2C	-0.01	0.13	-9999	-0.37	31	31
MEF2A	-0.001	0.11	-9999	-0.34	30	30
EIF4EBP1	0.001	0.12	-9999	-0.36	30	30
KRT19	-0.002	0.11	-9999	-0.34	31	31
ELK4	-0.001	0.11	-9999	-0.34	30	30
ATF6	-0.001	0.11	-9999	-0.34	30	30
ATF1	0.001	0.12	-9999	-0.36	30	30
p38alpha-beta/MAPKAPK2	0.002	0.12	-9999	-0.58	4	4
p38alpha-beta/MAPKAPK3	0.002	0.12	-9999	-0.58	4	4

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.007	0.06	-10000	0	-0.73	3	3
GNB1/GNG2	-0.068	0.058	-10000	0	-0.2	26	26
AKT1	-0.034	0.08	-10000	0	-0.21	5	5
EGF	-0.089	0.21	-10000	0	-0.49	91	91
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	-0.058	0.087	-10000	0	-0.32	3	3
mol:Ca2+	-0.063	0.11	-10000	0	-0.29	26	26
LYN	-0.056	0.084	-10000	0	-10000	0	0
RhoA/GTP	-0.031	0.043	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.068	0.12	-10000	0	-0.35	15	15
GNG2	-0.006	0.09	-10000	0	-0.44	19	19
ARRB2	0.012	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.005	0.064	-10000	0	-0.39	6	6
G beta5/gamma2	-0.085	0.075	-10000	0	-0.26	26	26
PRKCH	-0.066	0.12	-10000	0	-0.36	13	13
DNM1	0.004	0.077	-10000	0	-0.73	5	5
TXA2/TP beta/beta Arrestin3	-0.025	0.031	-10000	0	-0.26	3	3
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.24	0.22	-10000	0	-0.44	251	251
G12 family/GTP	-0.081	0.092	-10000	0	-0.29	26	26
ADRBK1	0.012	0	-10000	0	-10000	0	0
ADRBK2	0.011	0.021	-10000	0	-0.44	1	1
RhoA/GTP/ROCK1	0.016	0.013	-10000	0	-0.25	1	1
mol:GDP	0.073	0.089	0.27	22	-10000	0	22
mol:NADP	-0.004	0.11	-10000	0	-0.73	10	10
RAB11A	0.012	0	-10000	0	-10000	0	0
PRKG1	-0.009	0.096	-10000	0	-0.44	22	22
mol:IP3	-0.078	0.13	-10000	0	-0.36	26	26
cell morphogenesis	0.015	0.013	-10000	0	-0.25	1	1
PLCB2	-0.1	0.17	-10000	0	-0.48	26	26
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.13	0.13	-10000	0	-0.32	10	10
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.061	0.091	-10000	0	-0.34	7	7
RHOA	0.012	0	-10000	0	-10000	0	0
PTGIR	0.011	0.035	-10000	0	-0.73	1	1
PRKCB1	-0.072	0.13	-10000	0	-0.34	26	26
GNAQ	0.01	0.03	-10000	0	-0.44	2	2
mol:L-citrulline	-0.004	0.11	-10000	0	-0.73	10	10
TXA2/TXA2-R family	-0.11	0.17	-10000	0	-0.5	26	26
LCK	-0.062	0.094	-10000	0	-0.38	7	7
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.091	0.09	-10000	0	-0.36	2	2
TXA2-R family/G12 family/GDP/G beta/gamma	-0.016	0.048	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.077	0.097	-10000	0	-10000	0	0
MAPK14	-0.042	0.088	-10000	0	-0.24	9	9
TGM2/GTP	-0.093	0.15	-10000	0	-0.42	26	26
MAPK11	-0.043	0.09	-10000	0	-0.25	11	11
ARHGEF1	-0.033	0.07	-10000	0	-0.19	5	5
GNAI2	0.012	0	-10000	0	-10000	0	0
JNK cascade	-0.081	0.14	-10000	0	-0.37	26	26
RAB11/GDP	0.013	0.001	-10000	0	-10000	0	0
ICAM1	-0.053	0.1	-10000	0	-0.29	13	13
cAMP biosynthetic process	-0.084	0.13	-10000	0	-0.35	26	26
Gq family/GTP/EBP50	0.019	0.041	-10000	0	-0.58	1	1
actin cytoskeleton reorganization	0.015	0.013	-10000	0	-0.25	1	1
SRC	-0.056	0.084	-10000	0	-10000	0	0
GNB5	0.012	0	-10000	0	-10000	0	0
GNB1	0.012	0	-10000	0	-10000	0	0
EGF/EGFR	-0.082	0.097	-10000	0	-0.31	11	11
VCAM1	-0.06	0.11	-10000	0	-0.36	15	15
TP beta/Gq family/GDP/G beta5/gamma2	-0.005	0.064	-10000	0	-0.39	6	6
platelet activation	-0.057	0.12	-10000	0	-0.31	15	15
PGI2/IP	0.008	0.027	-10000	0	-0.56	1	1
PRKACA	-0.11	0.12	-10000	0	-0.28	2	2
Gq family/GDP/G beta5/gamma2	-0.016	0.068	-10000	0	-0.4	6	6
TXA2/TP beta/beta Arrestin2	-0.015	0.03	-10000	0	-0.29	4	4
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.098	0.11	-10000	0	-10000	0	0
mol:DAG	-0.081	0.14	-10000	0	-0.38	26	26
EGFR	0.011	0.021	-10000	0	-0.44	1	1
TXA2/TP alpha	-0.11	0.17	-10000	0	-0.48	26	26
Gq family/GTP	0.009	0.043	-10000	0	-0.35	3	3
YES1	-0.056	0.084	-10000	0	-10000	0	0
GNAI2/GTP	-0.083	0.075	-10000	0	-0.32	1	1
PGD2/DP	-0.17	0.16	-10000	0	-0.31	251	251
SLC9A3R1	0.012	0	-10000	0	-10000	0	0
FYN	-0.056	0.084	-10000	0	-10000	0	0
mol:NO	-0.004	0.11	-10000	0	-0.73	10	10
GNA15	0.004	0.077	-10000	0	-0.73	5	5
PGK/cGMP	-0.007	0.093	-10000	0	-0.33	31	31
RhoA/GDP	0.013	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.081	0.11	-10000	0	-0.38	17	17
NOS3	-0.004	0.11	-10000	0	-0.73	10	10
RAC1	0.012	0	-10000	0	-10000	0	0
PRKCA	-0.066	0.12	-10000	0	-0.35	13	13
PRKCB	-0.094	0.14	-10000	0	-0.41	18	18
PRKCE	-0.062	0.12	-10000	0	-0.34	13	13
PRKCD	-0.068	0.13	-10000	0	-0.38	13	13
PRKCG	-0.12	0.18	-10000	0	-0.46	51	51
muscle contraction	-0.1	0.17	-10000	0	-0.47	26	26
PRKCZ	-0.068	0.12	-10000	0	-0.35	15	15
ARR3	0	0.049	-10000	0	-0.73	2	2
TXA2/TP beta	-0.079	0.1	-10000	0	-0.36	1	1
PRKCQ	-0.065	0.12	-10000	0	-0.36	14	14
MAPKKK cascade	-0.093	0.15	-10000	0	-0.43	26	26
SELE	-0.076	0.14	-10000	0	-0.32	67	67
TP beta/GNAI2/GDP/G beta/gamma	-0.078	0.11	-10000	0	-10000	0	0
ROCK1	0.011	0.021	-10000	0	-0.44	1	1
GNA14	0.01	0.03	-10000	0	-0.44	2	2
chemotaxis	-0.11	0.19	-10000	0	-0.51	45	45
GNA12	0.012	0	-10000	0	-10000	0	0
GNA13	0.012	0	-10000	0	-10000	0	0
GNA11	0.01	0.03	-10000	0	-0.44	2	2
Rac1/GTP	0.008	0.002	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.001	0.077	-9999	-0.44	14	14
GNB1/GNG2	-0.04	0.13	-9999	-0.42	23	23
mol:DAG	-0.032	0.12	-9999	-0.4	13	13
PLCG1	-0.033	0.13	-9999	-0.42	13	13
YES1	-0.04	0.13	-9999	-0.44	18	18
FZD3	0.007	0.06	-9999	-0.73	3	3
FZD6	0.012	0	-9999	-10000	0	0
G protein	-0.032	0.13	-9999	-0.41	15	15
MAP3K7	-0.032	0.12	-9999	-0.41	5	5
mol:Ca2+	-0.031	0.12	-9999	-0.39	13	13
mol:IP3	-0.032	0.12	-9999	-0.4	13	13
NLK	0.007	0.011	-9999	-10000	0	0
GNB1	0.012	0	-9999	-10000	0	0
CAMK2A	-0.04	0.12	-9999	-0.45	5	5
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.049	0.14	-9999	-0.47	18	18
CSNK1A1	0.012	0	-9999	-10000	0	0
GNAS	-0.04	0.13	-9999	-0.44	18	18
GO:0007205	-0.032	0.12	-9999	-0.39	15	15
WNT6	-0.025	0.15	-9999	-0.62	26	26
WNT4	-0.009	0.1	-9999	-0.48	20	20
NFAT1/CK1 alpha	-0.026	0.13	-9999	-0.58	4	4
GNG2	-0.006	0.089	-9999	-0.44	19	19
WNT5A	0.003	0.08	-9999	-0.68	6	6
WNT11	-0.13	0.29	-9999	-0.7	94	94
CDC42	-0.033	0.12	-9999	-0.42	19	19

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.006	0.069	-9999	-0.73	4	4
GPC2	-0.012	0.13	-9999	-0.73	15	15
GPC2/Midkine	-0.005	0.11	-9999	-0.55	19	19
neuron projection morphogenesis	-0.005	0.11	-9999	-0.55	19	19

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.017	0.017	-10000	0	-10000	0	0
HSPA8	0.011	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.026	0.11	-10000	0	-0.4	14	14
AKT1	-0.017	0.039	-10000	0	-10000	0	0
GSC	-0.045	0.16	-10000	0	-0.53	44	44
NKX2-5	-0.018	0.12	-10000	0	-0.73	12	12
muscle cell differentiation	0.034	0.076	0.43	6	-10000	0	6
SMAD2-3/SMAD4/SP1	-0.025	0.099	-10000	0	-0.42	4	4
SMAD4	-0.007	0.055	-10000	0	-0.56	2	2
CBFB	0.012	0	-10000	0	-10000	0	0
SAP18	0.012	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.12	0.23	-10000	0	-0.47	136	136
SMAD3/SMAD4/VDR	0.036	0.045	-10000	0	-10000	0	0
MYC	0.03	0.098	-10000	0	-0.7	7	7
CDKN2B	-0.49	0.65	-10000	0	-1.3	183	183
AP1	0.027	0.059	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.029	0.039	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.12	0.19	-10000	0	-0.41	66	66
SP3	0.014	0	-10000	0	-10000	0	0
CREB1	0.012	0	-10000	0	-10000	0	0
FOXH1	-0.009	0.095	-10000	0	-0.49	15	15
SMAD3/SMAD4/GR	-0.006	0.11	-10000	0	-0.43	10	10
GATA3	0.002	0.064	-10000	0	-0.51	5	5
SKI/SIN3/HDAC complex/NCoR1	0.037	0.013	-10000	0	-10000	0	0
MEF2C/TIF2	-0.017	0.12	-10000	0	-0.49	12	12
endothelial cell migration	0.087	0.24	0.52	102	-10000	0	102
MAX	0.019	0.015	-10000	0	-10000	0	0
RBBP7	0.012	0.002	-10000	0	-10000	0	0
RBBP4	0.012	0.002	-10000	0	-10000	0	0
RUNX2	0.012	0	-10000	0	-10000	0	0
RUNX3	0.011	0.021	-10000	0	-0.44	1	1
RUNX1	0.012	0	-10000	0	-10000	0	0
CTBP1	0.012	0	-10000	0	-10000	0	0
NR3C1	-0.013	0.12	-10000	0	-0.44	32	32
VDR	0.012	0	-10000	0	-10000	0	0
CDKN1A	0.015	0.11	-10000	0	-1.3	2	2
KAT2B	-0.004	0.086	-10000	0	-0.42	18	18
SMAD2/SMAD2/SMAD4/FOXH1	-0.024	0.091	-10000	0	-0.45	5	5
DCP1A	0.012	0	-10000	0	-10000	0	0
SKI	0.012	0.002	-10000	0	-10000	0	0
SERPINE1	-0.087	0.24	-10000	0	-0.53	102	102
SMAD3/SMAD4/ATF2	0.009	0.057	-10000	0	-0.38	3	3
SMAD3/SMAD4/ATF3	0.006	0.07	-10000	0	-0.43	6	6
SAP30	0.012	0.002	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.041	0.039	-10000	0	-10000	0	0
JUN	0.026	0.058	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	0.009	0.058	-10000	0	-0.4	2	2
TFE3	0.009	0.016	-10000	0	-10000	0	0
COL1A2	-0.026	0.15	-10000	0	-0.58	30	30
mesenchymal cell differentiation	-0.009	0.057	0.39	2	-10000	0	2
DLX1	-0.017	0.14	-10000	0	-0.73	16	16
TCF3	0.012	0	-10000	0	-10000	0	0
FOS	0.008	0.057	-10000	0	-0.44	7	7
SMAD3/SMAD4/Max	0.013	0.062	-10000	0	-0.38	3	3
Cbp/p300/SNIP1	0.027	0.016	-10000	0	-10000	0	0
ZBTB17	0.033	0.036	-10000	0	-0.44	1	1
LAMC1	0.015	0.05	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0	0.089	-10000	0	-0.48	11	11
IRF7	0.012	0.021	-10000	0	-0.44	1	1
ESR1	-0.029	0.13	-10000	0	-0.44	42	42
HNF4A	0.012	0	-10000	0	-10000	0	0
MEF2C	-0.024	0.12	-10000	0	-0.49	18	18
SMAD2-3/SMAD4	-0.021	0.083	-10000	0	-0.42	4	4
Cbp/p300/Src-1	0.033	0.025	-10000	0	-10000	0	0
IGHV3OR16-13	0	0.01	-10000	0	-10000	0	0
TGIF2/HDAC complex	-0.001	0.097	-10000	0	-0.73	8	8
CREBBP	0.016	0.011	-10000	0	-10000	0	0
SKIL	0.011	0.021	-10000	0	-0.44	1	1
HDAC1	0.012	0.002	-10000	0	-10000	0	0
HDAC2	0.012	0.002	-10000	0	-10000	0	0
SNIP1	0.011	0.004	-10000	0	-10000	0	0
GCN5L2	0.004	0.014	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.011	0.059	-10000	0	-0.39	2	2
MSG1/HSC70	-0.16	0.26	-10000	0	-0.55	136	136
SMAD2	-0.022	0.052	-10000	0	-0.46	2	2
SMAD3	0.002	0.054	-10000	0	-0.48	3	3
SMAD3/E2F4-5/DP1/p107/SMAD4	0.017	0.055	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.006	0.067	-10000	0	-0.3	20	20
NCOR1	0.012	0.002	-10000	0	-10000	0	0
NCOA2	0.011	0.021	-10000	0	-0.44	1	1
NCOA1	0.012	0	-10000	0	-10000	0	0
MYOD/E2A	0.009	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	-0.02	0.097	-10000	0	-0.41	3	3
IFNB1	0.013	0.052	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	-0.028	0.13	-10000	0	-0.51	13	13
CITED1	-0.21	0.34	-10000	0	-0.73	136	136
SMAD2-3/SMAD4/ARC105	-0.01	0.075	-10000	0	-0.39	2	2
RBL1	0.012	0.001	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.16	0.26	-10000	0	-0.48	183	183
RUNX1-3/PEBPB2	0.025	0.013	-10000	0	-10000	0	0
SMAD7	0.007	0.087	-10000	0	-0.66	1	1
MYC/MIZ-1	0.06	0.1	-10000	0	-0.48	8	8
SMAD3/SMAD4	0.028	0.14	0.33	8	-10000	0	8
IL10	-0.004	0.14	-10000	0	-0.51	26	26
PIASy/HDAC complex	0.01	0.012	-10000	0	-10000	0	0
PIAS3	0.014	0.006	-10000	0	-10000	0	0
CDK2	0.016	0.011	-10000	0	-10000	0	0
IL5	0.002	0.11	-10000	0	-0.6	8	8
CDK4	0.015	0.037	-10000	0	-0.72	1	1
PIAS4	0.01	0.012	-10000	0	-10000	0	0
ATF3	0.007	0.06	-10000	0	-0.73	3	3
SMAD3/SMAD4/SP1	-0.004	0.076	-10000	0	-0.42	3	3
FOXG1	-0.1	0.26	-10000	0	-0.73	66	66
FOXO3	-0.017	0.05	-10000	0	-10000	0	0
FOXO1	-0.018	0.053	-10000	0	-0.39	1	1
FOXO4	-0.017	0.05	-10000	0	-10000	0	0
heart looping	-0.024	0.12	-10000	0	-0.48	18	18
CEBPB	-0.003	0.021	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.011	0.11	-10000	0	-0.47	19	19
MYOD1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	0.009	0.057	-10000	0	-0.38	3	3
SMAD3/SMAD4/GATA3	-0.001	0.096	-10000	0	-0.51	4	4
SnoN/SIN3/HDAC complex/NCoR1	0.011	0.021	-10000	0	-0.44	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.018	0.051	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.009	0.069	-10000	0	-0.39	1	1
MED15	0.011	0.021	-10000	0	-0.44	1	1
SP1	0.001	0.035	-10000	0	-10000	0	0
SIN3B	0.012	0.002	-10000	0	-10000	0	0
SIN3A	0.012	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.029	0.11	-10000	0	-0.47	14	14
ITGB5	0.021	0.063	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.039	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.009	0.094	-10000	0	-0.42	10	10
AR	-0.016	0.11	-10000	0	-0.46	26	26
negative regulation of cell growth	0.019	0.064	-10000	0	-0.39	3	3
SMAD3/SMAD4/MYOD	0.002	0.057	-10000	0	-0.38	3	3
E2F5	-0.001	0.097	-10000	0	-0.73	8	8
E2F4	0.012	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.002	0.074	-10000	0	-0.45	3	3
SMAD2-3/SMAD4/FOXO1-3a-4	-0.1	0.19	-10000	0	-0.34	113	113
TFDP1	0.012	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.019	0.061	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	0.009	0.057	-10000	0	-0.4	2	2
TGIF2	-0.001	0.097	-10000	0	-0.73	8	8
TGIF1	0.012	0	-10000	0	-10000	0	0
ATF2	0.012	0.001	-10000	0	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.015	0.027	-9999	-0.49	1	1
ARNO/beta Arrestin1-2	-0.012	0.073	-9999	-10000	0	0
EGFR	0.011	0.021	-9999	-0.44	1	1
EPHA2	0.011	0.035	-9999	-0.73	1	1
USP6	0.011	0.035	-9999	-0.73	1	1
IQSEC1	0.012	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.056	0.15	-9999	-0.35	92	92
ARRB2	0.008	0.002	-9999	-10000	0	0
mol:GTP	0.012	0.027	-9999	-0.25	2	2
ARRB1	0.011	0.021	-9999	-0.44	1	1
FBXO8	0.01	0.03	-9999	-0.44	2	2
TSHR	0.002	0.055	-9999	-0.44	7	7
EGF	-0.089	0.21	-9999	-0.49	91	91
somatostatin receptor activity	0	0	-9999	-0.001	19	19
ARAP2	0.011	0.021	-9999	-0.44	1	1
mol:GDP	-0.047	0.091	-9999	-0.24	42	42
mol:PI-3-4-5-P3	0	0	-9999	-0.001	5	5
ITGA2B	-0.02	0.15	-9999	-0.73	19	19
ARF6	0.012	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.03	0.024	-9999	-0.43	1	1
ADAP1	0.011	0.021	-9999	-0.44	1	1
KIF13B	0.01	0.03	-9999	-0.44	2	2
HGF/MET	0.005	0.077	-9999	-0.41	14	14
PXN	0.012	0	-9999	-10000	0	0
ARF6/GTP	-0.039	0.089	-9999	-0.26	19	19
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.039	0.13	-9999	-0.47	17	17
ADRB2	-0.062	0.17	-9999	-0.44	75	75
receptor agonist activity	0	0	-9999	0	20	20
actin filament binding	0	0	-9999	0	19	19
SRC	0.012	0	-9999	-10000	0	0
ITGB3	0.007	0.047	-9999	-0.44	5	5
GNAQ	0.01	0.03	-9999	-0.44	2	2
EFA6/PI-4-5-P2	0	0	-9999	-0.001	16	16
ARF6/GDP	0.007	0.079	-9999	-0.32	17	17
ARF6/GDP/GULP/ACAP1	-0.043	0.11	-9999	-0.37	16	16
alphaIIb/beta3 Integrin/paxillin/GIT1	0.009	0.095	-9999	-0.43	19	19
ACAP1	-0.007	0.092	-9999	-0.44	20	20
ACAP2	0.011	0.021	-9999	-0.44	1	1
LHCGR/beta Arrestin2	0.001	0.004	-9999	-10000	0	0
EFNA1	0.012	0	-9999	-10000	0	0
HGF	0.003	0.068	-9999	-0.47	9	9
CYTH3	0.009	0	-9999	-10000	0	0
CYTH2	0.008	0.002	-9999	-10000	0	0
NCK1	0.012	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	8	8
endosomal lumen acidification	0	0	-9999	-0.001	2	2
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.009	0.096	-9999	-0.44	22	22
GNAQ/ARNO	0.014	0.015	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	2	2
MET	0.004	0.077	-9999	-0.73	5	5
GNA14	0.01	0.03	-9999	-0.44	2	2
GNA15	0.004	0.077	-9999	-0.73	5	5
GIT1	0.011	0.021	-9999	-0.44	1	1
mol:PI-4-5-P2	0	0	-9999	-0.001	16	16
GNA11	0.01	0.03	-9999	-0.44	2	2
LHCGR	0.001	0.004	-9999	-10000	0	0
AGTR1	-0.14	0.21	-9999	-0.44	156	156
desensitization of G-protein coupled receptor protein signaling pathway	0.001	0.004	-9999	-10000	0	0
IPCEF1/ARNO	-0.028	0.1	-9999	-0.37	17	17
alphaIIb/beta3 Integrin	-0.01	0.12	-9999	-0.5	24	24

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.012	0	-10000	0	-10000	0	0
HDAC4	0.012	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.011	0.06	0.55	5	-10000	0	5
CDKN1A	-0.003	0.042	-10000	0	-0.64	2	2
KAT2B	-0.005	0.087	-10000	0	-0.44	18	18
BAX	0.012	0	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
FOXO1	0.011	0.021	-10000	0	-0.44	1	1
FOXO4	0.019	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.012	0	-10000	0	-10000	0	0
TAT	-0.17	0.22	-10000	0	-0.44	178	178
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.003	0.062	-10000	0	-0.31	18	18
PPARGC1A	-0.045	0.15	-10000	0	-0.44	58	58
FHL2	0.012	0	-10000	0	-10000	0	0
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.016	0.008	-10000	0	-10000	0	0
HIST2H4A	0.011	0.06	-10000	0	-0.55	5	5
SIRT1/FOXO3a	0.001	0.009	-10000	0	-10000	0	0
SIRT1	0.009	0.012	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.023	0.007	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.004	0.059	-10000	0	-10000	0	0
apoptosis	-0.022	0.007	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.02	0.088	-10000	0	-0.25	56	56
p53/SIRT1	0.002	0.024	0.37	2	-10000	0	2
SIRT1/FOXO4	0.02	0.009	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	0.021	0.013	-10000	0	-10000	0	0
HIST1H1E	0	0.068	-10000	0	-0.24	33	33
SIRT1/p300	0.016	0.008	-10000	0	-10000	0	0
muscle cell differentiation	-0.004	0.053	-10000	0	-10000	0	0
TP53	0.009	0.012	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.023	0.007	-10000	0	-10000	0	0
CREBBP	0.012	0	-10000	0	-10000	0	0
MEF2D	0.012	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.11	0.15	-10000	0	-0.3	177	177
ACSS2	0.017	0.008	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.004	0.053	-10000	0	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.011	0.17	-9999	-0.65	4	4
CRP	-0.018	0.17	-9999	-0.77	5	5
cell cycle arrest	-0.023	0.18	-9999	-0.67	10	10
TIMP1	-0.032	0.21	-9999	-0.59	28	28
IL6ST	0.007	0.063	-9999	-0.44	9	9
Rac1/GDP	-0.047	0.15	-9999	-0.49	16	16
AP1	0.026	0.064	-9999	-10000	0	0
GAB2	0.013	0.002	-9999	-10000	0	0
TNFSF11	-0.028	0.21	-9999	-0.78	14	14
HSP90B1	0.024	0.038	-9999	-10000	0	0
GAB1	0.013	0.001	-9999	-10000	0	0
MAPK14	-0.041	0.13	-9999	-0.47	10	10
AKT1	0.047	0.011	-9999	-10000	0	0
FOXO1	0.05	0.014	-9999	-10000	0	0
MAP2K6	-0.05	0.14	-9999	-0.44	20	20
mol:GTP	0	0.002	-9999	-10000	0	0
MAP2K4	-0.033	0.16	-9999	-0.49	16	16
MITF	-0.053	0.15	-9999	-0.44	25	25
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.012	0	-9999	-10000	0	0
A2M	0.007	0.12	-9999	-1.3	4	4
CEBPB	0.018	0.004	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0	0.065	-9999	-10000	0	0
STAT3	-0.026	0.19	-9999	-0.69	11	11
STAT1	-0.004	0.017	-9999	-10000	0	0
CEBPD	-0.012	0.17	-9999	-0.76	4	4
PIK3CA	0.014	0.001	-9999	-10000	0	0
PI3K	0.021	0.001	-9999	-10000	0	0
JUN	0.012	0.001	-9999	-10000	0	0
PIAS3/MITF	-0.045	0.14	-9999	-0.46	16	16
MAPK11	-0.043	0.14	-9999	-0.49	12	12
STAT3 (dimer)/FOXO1	0.013	0.16	-9999	-0.56	2	2
GRB2/SOS1/GAB family	-0.067	0.12	-9999	-0.51	12	12
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.064	0.16	-9999	-0.49	27	27
GRB2	0.013	0.001	-9999	-10000	0	0
JAK2	0.009	0.036	-9999	-0.44	3	3
LBP	-0.037	0.21	-9999	-0.62	19	19
PIK3R1	0.013	0	-9999	-10000	0	0
JAK1	0.014	0.021	-9999	-0.43	1	1
MYC	-0.015	0.18	-9999	-0.65	5	5
FGG	-0.043	0.22	-9999	-0.71	12	12
macrophage differentiation	-0.023	0.18	-9999	-0.67	10	10
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.084	0.19	-9999	-0.42	84	84
JUNB	-0.013	0.17	-9999	-0.78	5	5
FOS	0.005	0.055	-9999	-0.44	7	7
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.058	0.15	-9999	-0.42	31	31
STAT1/PIAS1	-0.037	0.14	-9999	-0.41	21	21
GRB2/SOS1/GAB family/SHP2/PI3K	0.038	0.012	-9999	-10000	0	0
STAT3 (dimer)	-0.025	0.19	-9999	-0.7	10	10
PRKCD	-0.021	0.16	-9999	-0.52	10	10
IL6R	-0.085	0.19	-9999	-0.43	102	102
SOCS3	-0.038	0.13	-9999	-0.63	3	3
gp130 (dimer)/JAK1/JAK1/LMO4	0.028	0.046	-9999	-10000	0	0
Rac1/GTP	-0.044	0.15	-9999	-0.48	17	17
HCK	0	0.072	-9999	-0.44	12	12
MAPKKK cascade	0.018	0.05	-9999	-10000	0	0
bone resorption	-0.025	0.2	-9999	-0.73	14	14
IRF1	-0.011	0.17	-9999	-0.65	4	4
mol:GDP	-0.057	0.16	-9999	-0.43	33	33
SOS1	0.013	0.002	-9999	-10000	0	0
VAV1	-0.058	0.16	-9999	-0.43	33	33
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.08	0.18	-9999	-0.55	21	21
PTPN11	-0.003	0.013	-9999	-10000	0	0
IL6/IL6RA	-0.14	0.23	-9999	-0.42	166	166
gp130 (dimer)/TYK2/TYK2/LMO4	0.023	0.042	-9999	-10000	0	0
gp130 (dimer)/JAK2/JAK2/LMO4	0.022	0.05	-9999	-0.49	1	1
IL6	-0.1	0.27	-9999	-0.7	77	77
PIAS3	0.012	0	-9999	-10000	0	0
PTPRE	0.007	0.009	-9999	-10000	0	0
PIAS1	0.012	0	-9999	-10000	0	0
RAC1	0.013	0.001	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.067	0.14	-9999	-0.38	32	32
LMO4	0.014	0.022	-9999	-0.44	1	1
STAT3 (dimer)/PIAS3	-0.023	0.18	-9999	-0.66	10	10
MCL1	0.051	0.01	-9999	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.012	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.024	0.096	-10000	0	-0.35	15	15
NT3 (dimer)/TRKC	-0.046	0.13	-10000	0	-0.31	87	87
NT3 (dimer)/TRKB	-0.13	0.19	-10000	0	-0.5	64	64
SHC/Grb2/SOS1/GAB1/PI3K	0.032	0	-10000	0	-10000	0	0
RAPGEF1	0.011	0.021	-10000	0	-0.44	1	1
BDNF	-0.009	0.12	-10000	0	-0.73	13	13
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
DYNLT1	0.012	0	-10000	0	-10000	0	0
NTRK1	0.005	0.069	-10000	0	-0.73	4	4
NTRK2	-0.12	0.22	-10000	0	-0.46	131	131
NTRK3	-0.071	0.17	-10000	0	-0.44	83	83
NT-4/5 (dimer)/TRKB	-0.15	0.2	-10000	0	-0.51	78	78
neuron apoptosis	0.12	0.17	0.42	82	-10000	0	82
SHC 2-3/Grb2	-0.13	0.19	-10000	0	-0.46	82	82
SHC1	0.012	0	-10000	0	-10000	0	0
SHC2	-0.12	0.15	-10000	0	-0.44	66	66
SHC3	-0.14	0.18	-10000	0	-0.46	86	86
STAT3 (dimer)	0.018	0.025	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.056	0.13	-10000	0	-0.48	7	7
RIN/GDP	-0.005	0.067	-10000	0	-0.28	1	1
GIPC1	0.011	0.021	-10000	0	-0.44	1	1
KRAS	0.012	0	-10000	0	-10000	0	0
DNAJA3	-0.062	0.13	-10000	0	-0.46	8	8
RIN/GTP	-0.001	0.026	-10000	0	-0.56	1	1
CCND1	0.022	0.052	-10000	0	-0.61	3	3
MAGED1	0.012	0	-10000	0	-10000	0	0
PTPN11	0.012	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.026	0.15	-10000	0	-0.73	19	19
SHC/GRB2/SOS1	0.025	0	-10000	0	-10000	0	0
GRB2	0.012	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.023	0.11	-10000	0	-0.48	6	6
TRKA/NEDD4-2	0.012	0.055	-10000	0	-0.5	5	5
ELMO1	0.009	0.036	-10000	0	-0.44	3	3
RhoG/GTP/ELMO1/DOCK1	0.015	0.022	-10000	0	-0.25	3	3
NGF	-0.006	0.089	-10000	0	-0.45	17	17
HRAS	0.011	0.021	-10000	0	-0.44	1	1
DOCK1	0.012	0	-10000	0	-10000	0	0
GAB2	0.012	0	-10000	0	-10000	0	0
RIT2	-0.001	0.034	-10000	0	-0.73	1	1
RIT1	0.012	0	-10000	0	-10000	0	0
FRS2	0.012	0.001	-10000	0	-10000	0	0
DNM1	0.004	0.077	-10000	0	-0.73	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.012	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.061	0.13	-10000	0	-0.44	8	8
mol:GDP	-0.007	0.091	-10000	0	-0.34	1	1
NGF (dimer)	-0.006	0.089	-10000	0	-0.45	17	17
RhoG/GDP	0.007	0.026	-10000	0	-0.31	3	3
RIT1/GDP	0.001	0.066	-10000	0	-10000	0	0
TIAM1	-0.03	0.13	-10000	0	-0.44	43	43
PIK3R1	0.012	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.071	0.15	-10000	0	-0.48	22	22
KIDINS220/CRKL/C3G	0.018	0.015	-10000	0	-0.3	1	1
SHC/RasGAP	0.018	0	-10000	0	-10000	0	0
FRS2 family/SHP2	0.024	0.024	-10000	0	-0.48	1	1
SHC/GRB2/SOS1/GAB1	0.032	0	-10000	0	-10000	0	0
RIT1/GTP	0.009	0	-10000	0	-10000	0	0
NT3 (dimer)	0.004	0.059	-10000	0	-0.44	8	8
RAP1/GDP	-0.022	0.039	-10000	0	-10000	0	0
KIDINS220/CRKL	0.012	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.009	0.12	-10000	0	-0.73	13	13
ubiquitin-dependent protein catabolic process	0.008	0.072	-10000	0	-0.47	5	5
Schwann cell development	-0.028	0.029	-10000	0	-10000	0	0
EHD4	0.012	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.031	0.022	-10000	0	-0.44	1	1
FRS2 family/SHP2/CRK family/C3G/GAB2	0.034	0.015	-10000	0	-10000	0	0
RAP1B	0.012	0	-10000	0	-10000	0	0
RAP1A	0.012	0	-10000	0	-10000	0	0
CDC42/GTP	-0.098	0.14	-10000	0	-0.39	56	56
ABL1	0.012	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.018	0	-10000	0	-10000	0	0
Rap1/GTP	0	0.068	-10000	0	-10000	0	0
STAT3	0.018	0.025	-10000	0	-10000	0	0
axon guidance	-0.094	0.13	-10000	0	-0.38	56	56
MAPK3	-0.015	0.099	-10000	0	-0.43	6	6
MAPK1	-0.015	0.098	-10000	0	-0.43	6	6
CDC42/GDP	0.001	0.067	-10000	0	-0.29	1	1
NTF3	0.004	0.059	-10000	0	-0.44	8	8
NTF4	-0.026	0.15	-10000	0	-0.73	19	19
NGF (dimer)/TRKA/FAIM	0.009	0.071	-10000	0	-0.47	5	5
PI3K	0.018	0	-10000	0	-10000	0	0
FRS3	0.011	0.035	-10000	0	-0.73	1	1
FAIM	0.012	0.001	-10000	0	-10000	0	0
GAB1	0.012	0	-10000	0	-10000	0	0
RASGRF1	-0.089	0.16	-10000	0	-0.45	40	40
SOS1	0.012	0	-10000	0	-10000	0	0
MCF2L	-0.032	0.11	-10000	0	-0.48	4	4
RGS19	0.011	0.021	-10000	0	-0.44	1	1
CDC42	0.011	0.021	-10000	0	-0.44	1	1
RAS family/GTP	0.007	0.068	-10000	0	-0.43	1	1
Rac1/GDP	0.001	0.066	-10000	0	-10000	0	0
NGF (dimer)/TRKA/GRIT	0	0.071	-10000	0	-0.31	21	21
neuron projection morphogenesis	-0.052	0.14	-10000	0	-0.46	8	8
NGF (dimer)/TRKA/NEDD4-2	0.008	0.072	-10000	0	-0.47	5	5
MAP2K1	0.033	0	-10000	0	-10000	0	0
NGFR	-0.11	0.2	-10000	0	-0.44	121	121
NGF (dimer)/TRKA/GIPC/GAIP	0.017	0.057	-10000	0	-10000	0	0
RAS family/GTP/PI3K	0.025	0.019	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0.036	0.021	-10000	0	-0.41	1	1
NRAS	0.01	0.03	-10000	0	-0.44	2	2
GRB2/SOS1	0.018	0	-10000	0	-10000	0	0
PRKCI	0.01	0.03	-10000	0	-0.44	2	2
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.012	0	-10000	0	-10000	0	0
PRKCZ	0.012	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.051	0.12	-10000	0	-0.61	16	16
RASA1	0.012	0.001	-10000	0	-10000	0	0
TRKA/c-Abl	0.012	0.053	-10000	0	-0.55	4	4
SQSTM1	0.012	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.057	0.14	-10000	0	-0.44	22	22
NGF (dimer)/TRKA/p62/Atypical PKCs	0.021	0.066	-10000	0	-0.44	5	5
MATK	-0.04	0.14	-10000	0	-0.44	53	53
NEDD4L	0.011	0.021	-10000	0	-0.44	1	1
RAS family/GDP	-0.019	0.038	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.083	0.13	-10000	0	-0.29	121	121
Rac1/GTP	-0.076	0.1	-10000	0	-0.34	24	24
FRS2 family/SHP2/CRK family	0.036	0.021	-10000	0	-0.41	1	1

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.027	0.046	-10000	0	-0.52	3	3
epithelial cell differentiation	-0.016	0.064	-10000	0	-0.63	1	1
ITCH	0.013	0.005	-10000	0	-10000	0	0
WWP1	0.027	0.06	-10000	0	-1.3	1	1
FYN	0.012	0	-10000	0	-10000	0	0
EGFR	0.011	0.021	-10000	0	-0.44	1	1
PRL	-0.014	0.12	-10000	0	-0.73	12	12
neuron projection morphogenesis	0.026	0.074	-10000	0	-0.47	1	1
PTPRZ1	-0.14	0.21	-10000	0	-0.44	152	152
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.018	0.078	-10000	0	-0.52	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.001	0.087	-10000	0	-0.6	1	1
ADAM17	0.013	0.005	-10000	0	-10000	0	0
ErbB4/ErbB4	0.029	0.037	-10000	0	-0.74	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.024	0.04	-10000	0	-0.56	2	2
NCOR1	0.012	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.006	0.082	-10000	0	-0.57	1	1
GRIN2B	-0.096	0.19	-10000	0	-0.57	9	9
ErbB4/ErbB2/betacellulin	0.029	0.055	-10000	0	-0.43	5	5
STAT1	0.011	0.035	-10000	0	-0.73	1	1
HBEGF	0.009	0.049	-10000	0	-0.73	2	2
PRLR	0.003	0.062	-10000	0	-0.44	9	9
E4ICDs/ETO2	-0.007	0.095	-10000	0	-0.56	2	2
axon guidance	0.056	0.083	-10000	0	-0.75	1	1
NEDD4	0.013	0.006	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.008	0.1	-10000	0	-0.45	21	21
CBFA2T3	-0.051	0.16	-10000	0	-0.44	64	64
ErbB4/ErbB2/HBEGF	0.03	0.057	-10000	0	-0.42	7	7
MAPK3	0.021	0.076	-10000	0	-0.49	1	1
STAT1 (dimer)	0.028	0.04	-10000	0	-0.56	2	2
MAPK1	0.022	0.075	-10000	0	-0.49	1	1
JAK2	0.009	0.036	-10000	0	-0.44	3	3
ErbB4/ErbB2/neuregulin 1 beta	0.001	0.092	-10000	0	-0.47	5	5
NRG1	-0.023	0.11	-10000	0	-0.31	60	60
NRG3	0.005	0.035	-10000	0	-0.73	1	1
NRG2	-0.05	0.15	-10000	0	-0.44	59	59
NRG4	-0.038	0.14	-10000	0	-0.44	49	49
heart development	0.056	0.083	-10000	0	-0.75	1	1
neural crest cell migration	0.001	0.091	-10000	0	-0.47	5	5
ERBB2	0.015	0.054	-10000	0	-0.56	4	4
WWOX/E4ICDs	0.029	0.033	-10000	0	-0.67	1	1
SHC1	0.012	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.007	0.079	-10000	0	-0.63	1	1
apoptosis	0.024	0.056	0.62	1	-10000	0	1
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.006	0.092	-10000	0	-0.56	2	2
ErbB4/ErbB2/epiregulin	-0.14	0.21	-10000	0	-0.4	180	180
ErbB4/ErbB4/betacellulin/betacellulin	0.027	0.043	-10000	0	-0.67	1	1
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.023	0.084	-10000	0	-0.52	2	2
MDM2	0.031	0.036	-10000	0	-0.67	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.001	0.082	-10000	0	-0.53	1	1
STAT5A	0.061	0.076	-10000	0	-0.72	1	1
ErbB4/EGFR/neuregulin 1 beta	0.005	0.082	-10000	0	-0.57	1	1
DLG4	0.011	0.035	-10000	0	-0.73	1	1
GRB2/SHC	0.018	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.027	0.031	-10000	0	-0.63	1	1
STAT5A (dimer)	-0.017	0.069	-10000	0	-0.69	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.058	0.073	-10000	0	-0.72	1	1
LRIG1	0.012	0	-10000	0	-10000	0	0
EREG	-0.29	0.36	-10000	0	-0.71	188	188
BTC	0.007	0.047	-10000	0	-0.44	5	5
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.057	0.083	-10000	0	-0.76	1	1
ERBB4	0.029	0.037	-10000	0	-0.74	1	1
STAT5B	0.012	0	-10000	0	-10000	0	0
YAP1	0.016	0.008	-10000	0	-10000	0	0
GRB2	0.012	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.006	0.084	-10000	0	-0.43	5	5
glial cell differentiation	-0.026	0.031	0.63	1	-10000	0	1
WWOX	0.012	0	-10000	0	-10000	0	0
cell proliferation	0.018	0.1	-10000	0	-0.57	2	2

×

Signaling events mediated by PTP1B

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
PDGFRB	0.004	0.077	-10000	0	-0.73	5	5
Jak2/Leptin Receptor	-0.033	0.072	-10000	0	-0.37	5	5
PTP1B/AKT1	-0.044	0.072	-10000	0	-10000	0	0
FYN	0.012	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.056	0.08	-10000	0	-0.29	1	1
EGFR	0.008	0.022	-10000	0	-0.45	1	1
EGF/EGFR	-0.088	0.13	-10000	0	-0.36	62	62
CSF1	0.01	0.03	-10000	0	-0.44	2	2
AKT1	0.012	0.001	-10000	0	-10000	0	0
INSR	0.012	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.061	0.092	-10000	0	-0.46	6	6
Insulin Receptor/Insulin	-0.04	0.042	-10000	0	-10000	0	0
HCK	0.001	0.072	-10000	0	-0.44	12	12
CRK	0.012	0	-10000	0	-10000	0	0
TYK2	-0.048	0.076	-10000	0	-0.27	1	1
EGF	-0.091	0.21	-10000	0	-0.5	91	91
YES1	0.011	0.021	-10000	0	-0.44	1	1
CAV1	-0.053	0.09	-10000	0	-0.31	1	1
TXN	0.011	0.003	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.04	0.074	-10000	0	-10000	0	0
cell migration	0.056	0.08	0.29	1	-10000	0	1
STAT3	0.012	0.001	-10000	0	-10000	0	0
PRLR	0.003	0.063	-10000	0	-0.44	9	9
ITGA2B	-0.02	0.15	-10000	0	-0.73	19	19
CSF1R	-0.018	0.11	-10000	0	-0.44	31	31
Prolactin Receptor/Prolactin	-0.01	0.1	-10000	0	-0.44	21	21
FGR	0.008	0.05	-10000	0	-0.51	4	4
PTP1B/p130 Cas	-0.048	0.077	-10000	0	-0.29	2	2
Crk/p130 Cas	-0.04	0.075	-10000	0	-0.29	1	1
DOK1	-0.036	0.074	-10000	0	-0.34	4	4
JAK2	-0.035	0.073	-10000	0	-0.36	8	8
Jak2/Leptin Receptor/Leptin	-0.055	0.078	-10000	0	-0.46	6	6
PIK3R1	0.012	0	-10000	0	-10000	0	0
PTPN1	-0.057	0.081	-10000	0	-0.3	1	1
LYN	0.012	0	-10000	0	-10000	0	0
CDH2	-0.014	0.11	-10000	0	-0.48	24	24
SRC	-0.009	0.034	-10000	0	-10000	0	0
ITGB3	0.007	0.047	-10000	0	-0.44	5	5
CAT1/PTP1B	-0.095	0.12	-10000	0	-0.36	26	26
CAPN1	0.012	0.002	-10000	0	-10000	0	0
CSK	0.012	0	-10000	0	-10000	0	0
PI3K	-0.03	0.035	-10000	0	-10000	0	0
mol:H2O2	0.001	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.049	0.071	-10000	0	-0.44	4	4
negative regulation of transcription	-0.035	0.072	-10000	0	-0.36	8	8
FCGR2A	0.007	0.06	-10000	0	-0.73	3	3
FER	0.01	0.021	-10000	0	-0.44	1	1
alphaIIb/beta3 Integrin	-0.011	0.12	-10000	0	-0.5	24	24
BLK	-0.16	0.22	-10000	0	-0.44	173	173
Insulin Receptor/Insulin/Shc	0.017	0.001	-10000	0	-10000	0	0
RHOA	0.012	0.002	-10000	0	-10000	0	0
LEPR	0.006	0.051	-10000	0	-0.43	6	6
BCAR1	0.011	0.021	-10000	0	-0.44	1	1
p210 bcr-abl/Grb2	0.012	0	-10000	0	-10000	0	0
mol:NADPH	-0.001	0.003	-10000	0	-10000	0	0
TRPV6	-0.088	0.14	-10000	0	-0.41	34	34
PRL	-0.014	0.12	-10000	0	-0.73	12	12
SOCS3	0.014	0.029	-10000	0	-0.54	1	1
SPRY2	0.014	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.017	0.001	-10000	0	-10000	0	0
CSF1/CSF1R	-0.055	0.086	-10000	0	-0.35	6	6
Ras protein signal transduction	0.03	0.026	-10000	0	-10000	0	0
IRS1	0.012	0	-10000	0	-10000	0	0
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.03	0.14	-10000	0	-0.51	33	33
STAT5B	-0.044	0.072	-10000	0	-0.24	6	6
STAT5A	-0.044	0.072	-10000	0	-0.24	5	5
GRB2	0.012	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.052	0.093	-10000	0	-0.57	5	5
CSN2	0.01	0.05	-10000	0	-0.52	2	2
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
LAT	-0.013	0.053	-10000	0	-0.37	5	5
YBX1	0.019	0.002	-10000	0	-10000	0	0
LCK	-0.001	0.096	-10000	0	-0.66	9	9
SHC1	0.012	0	-10000	0	-10000	0	0
NOX4	-0.36	0.37	-10000	0	-0.73	232	232

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.034	0.1	0.35	13	-10000	0	13
GNAI2	0.012	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.009	0.061	-10000	0	-0.48	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.11	0.2	-10000	0	-0.44	125	125
RhoA/GTP	-0.035	0.11	-10000	0	-0.35	13	13
negative regulation of cAMP metabolic process	-0.044	0.12	-10000	0	-0.39	13	13
GNAZ	0.007	0.047	-10000	0	-0.44	5	5
GNAI3	0.012	0	-10000	0	-10000	0	0
GNA12	0.012	0	-10000	0	-10000	0	0
S1PR5	0.001	0.091	-10000	0	-0.73	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.045	0.12	-10000	0	-0.39	13	13
RhoA/GDP	0.009	0	-10000	0	-10000	0	0
RHOA	0.012	0	-10000	0	-10000	0	0
GNAI1	-0.001	0.077	-10000	0	-0.44	14	14

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.017	0.031	-9999	-0.42	2	2
PDGFRB	0.004	0.078	-9999	-0.73	5	5
SPHK1	-0.024	0.062	-9999	-0.24	32	32
mol:S1P	-0.025	0.061	-9999	-0.28	15	15
S1P1/S1P/Gi	-0.056	0.16	-9999	-0.47	25	25
GNAO1	-0.11	0.2	-9999	-0.44	125	125
PDGFB-D/PDGFRB/PLCgamma1	-0.042	0.14	-9999	-0.43	26	26
PLCG1	-0.047	0.15	-9999	-0.45	22	22
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.004	0.077	-9999	-0.73	5	5
GNAI2	0.012	0.004	-9999	-10000	0	0
GNAI3	0.012	0.004	-9999	-10000	0	0
GNAI1	-0.002	0.078	-9999	-0.44	14	14
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.014	0.027	-9999	-0.47	1	1
S1P1/S1P	0.007	0.072	-9999	-0.32	3	3
negative regulation of cAMP metabolic process	-0.054	0.15	-9999	-0.46	25	25
MAPK3	-0.053	0.17	-9999	-0.49	30	30
calcium-dependent phospholipase C activity	-0.001	0.002	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
RhoA/GDP	0.009	0	-9999	-10000	0	0
KDR	0.012	0.021	-9999	-0.43	1	1
PLCB2	0.012	0.067	-9999	-0.3	2	2
RAC1	0.012	0	-9999	-10000	0	0
RhoA/GTP	-0.014	0.055	-9999	-10000	0	0
receptor internalization	-0.015	0.061	-9999	-0.3	3	3
PTGS2	-0.056	0.2	-9999	-0.59	35	35
Rac1/GTP	-0.014	0.055	-9999	-0.28	2	2
RHOA	0.012	0	-9999	-10000	0	0
VEGFA	0.011	0.035	-9999	-0.73	1	1
negative regulation of T cell proliferation	-0.054	0.15	-9999	-0.46	25	25
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.007	0.047	-9999	-0.44	5	5
MAPK1	-0.052	0.17	-9999	-0.49	29	29
S1P1/S1P/PDGFB-D/PDGFRB	0.009	0.09	-9999	-0.46	7	7
ABCC1	0.012	0.002	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.02	0.064	0.38	5	-10000	0	5
RFC1	0.02	0.064	0.24	22	-10000	0	22
PRKDC	0.02	0.064	0.25	20	-10000	0	20
RIPK1	0.013	0.003	-10000	0	-10000	0	0
CASP7	-0.002	0.057	0.22	14	-0.55	1	15
FASLG/FAS/FADD/FAF1	-0.005	0.077	0.23	11	-0.29	5	16
MAP2K4	0.002	0.1	-10000	0	-0.36	7	7
mol:ceramide	-0.001	0.091	-10000	0	-0.38	6	6
GSN	0.015	0.064	0.25	17	-0.24	4	21
FASLG/FAS/FADD/FAF1/Caspase 8	0.007	0.081	0.28	1	-0.36	4	5
FAS	0.005	0.051	-10000	0	-0.44	6	6
BID	0.021	0.066	0.28	25	-0.48	1	26
MAP3K1	0.016	0.071	0.2	14	-0.32	1	15
MAP3K7	0.011	0.003	-10000	0	-10000	0	0
RB1	0.02	0.064	0.38	5	-10000	0	5
CFLAR	0.013	0.003	-10000	0	-10000	0	0
HGF/MET	-0.001	0.11	-10000	0	-0.48	18	18
ARHGDIB	0.02	0.064	0.38	5	-10000	0	5
FADD	0.011	0.005	-10000	0	-10000	0	0
actin filament polymerization	-0.015	0.064	0.24	4	-0.24	18	22
NFKB1	-0.028	0.055	-10000	0	-0.25	3	3
MAPK8	-0.007	0.13	-10000	0	-0.45	9	9
DFFA	0.02	0.064	0.25	20	-10000	0	20
DNA fragmentation during apoptosis	0.02	0.064	0.38	5	-10000	0	5
FAS/FADD/MET	0.013	0.061	-10000	0	-0.48	5	5
CFLAR/RIP1	0.015	0.007	-10000	0	-10000	0	0
FAIM3	-0.012	0.1	-10000	0	-0.44	25	25
FAF1	0.011	0.005	-10000	0	-10000	0	0
PARP1	0.02	0.064	0.25	20	-10000	0	20
DFFB	0.02	0.064	0.38	5	-10000	0	5
CHUK	-0.024	0.048	-10000	0	-10000	0	0
FASLG	-0.019	0.11	-10000	0	-0.45	30	30
FAS/FADD	0.012	0.037	-10000	0	-0.3	6	6
HGF	0.003	0.068	-10000	0	-0.47	9	9
LMNA	0.028	0.056	0.34	5	-10000	0	5
CASP6	0.02	0.064	0.38	5	-10000	0	5
CASP10	0.011	0.005	-10000	0	-10000	0	0
CASP3	0.023	0.077	0.25	40	-10000	0	40
PTPN13	-0.01	0.12	-10000	0	-0.67	15	15
CASP8	0.019	0.078	0.34	25	-10000	0	25
IL6	-0.072	0.24	-10000	0	-0.58	77	77
MET	0.004	0.077	-10000	0	-0.73	5	5
ICAD/CAD	0.018	0.059	0.34	5	-10000	0	5
FASLG/FAS/FADD/FAF1/Caspase 10	-0.002	0.092	-10000	0	-0.38	6	6
activation of caspase activity by cytochrome c	0.021	0.066	0.28	25	-0.48	1	26
PAK2	0.02	0.064	0.38	5	-10000	0	5
BCL2	-0.009	0.096	-10000	0	-0.44	22	22

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.012	0	-9999	-10000	0	0
HDAC3	0.012	0	-9999	-10000	0	0
VDR	0.012	0	-9999	-10000	0	0
Cbp/p300/PCAF	0.014	0.053	-9999	-10000	0	0
EP300	0.012	0	-9999	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.003	0.057	-9999	-0.37	1	1
KAT2B	-0.005	0.087	-9999	-0.44	18	18
MAPK14	0.012	0	-9999	-10000	0	0
AKT1	-0.005	0.063	-9999	-10000	0	0
RAR alpha/9cRA/Cyclin H	-0.051	0.073	-9999	-0.51	1	1
mol:9cRA	0	0	-9999	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.001	0.063	-9999	-0.29	9	9
CDC2	0	0.001	-9999	-10000	0	0
response to UV	0.001	0.002	-9999	-10000	0	0
RAR alpha/Jnk1	-0.041	0.087	-9999	-0.36	1	1
NCOR2	0.011	0.021	-9999	-0.44	1	1
VDR/VDR/Vit D3	0.009	0	-9999	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.068	0.13	-9999	-0.49	2	2
NCOA2	0.011	0.021	-9999	-0.44	1	1
NCOA3	0.012	0	-9999	-10000	0	0
NCOA1	0.012	0	-9999	-10000	0	0
VDR/VDR/DNA	0.012	0	-9999	-10000	0	0
RARG	0.013	0.001	-9999	-10000	0	0
RAR gamma1/9cRA	0.017	0.001	-9999	-10000	0	0
MAPK3	0.012	0.021	-9999	-0.44	1	1
MAPK1	0.012	0	-9999	-10000	0	0
MAPK8	0.013	0.002	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.085	0.13	-9999	-10000	0	0
RARA	-0.049	0.1	-9999	-0.4	1	1
negative regulation of phosphoinositide 3-kinase cascade	0	0	-9999	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.001	0.064	-9999	-0.29	9	9
PRKCA	0.015	0.004	-9999	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.083	0.13	-9999	-0.59	2	2
RXRG	-0.21	0.22	-9999	-0.36	280	280
RXRA	-0.039	0.097	-9999	-10000	0	0
RXRB	-0.085	0.15	-9999	-0.3	154	154
VDR/Vit D3/DNA	0.009	0	-9999	-10000	0	0
RBP1	-0.033	0.18	-9999	-0.73	28	28
CRBP1/9-cic-RA	-0.026	0.14	-9999	-0.56	28	28
RARB	0.01	0.042	-9999	-0.44	4	4
PRKCG	-0.24	0.35	-9999	-0.73	154	154
MNAT1	0.011	0.035	-9999	-0.73	1	1
RAR alpha/RXRs	-0.065	0.13	-9999	-10000	0	0
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.058	0.12	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.017	0.083	-9999	-0.36	1	1
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.083	0.13	-9999	-0.59	2	2
positive regulation of DNA binding	-0.049	0.069	-9999	-0.48	1	1
NRIP1	-0.08	0.14	-9999	-1.2	2	2
RXRs/RARs	-0.091	0.13	-9999	-0.42	2	2
RXRs/RXRs/DNA/9cRA	-0.094	0.14	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
CDK7	0.012	0	-9999	-10000	0	0
TFIIH	0.024	0.023	-9999	-0.47	1	1
RAR alpha/9cRA	-0.038	0.056	-9999	-0.5	1	1
CCNH	0.012	0	-9999	-10000	0	0
CREBBP	0.012	0	-9999	-10000	0	0
RAR gamma2/9cRA	-0.001	0.017	-9999	-0.37	1	1

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.012	0	-9999	-10000	0	0
PTK2	0.012	0	-9999	-10000	0	0
CRKL	-0.034	0.098	-9999	-10000	0	0
GRB2/SOS1/SHC	0.025	0	-9999	-10000	0	0
HRAS	0.011	0.021	-9999	-0.44	1	1
IRS1/Crk	-0.033	0.099	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/PTP1B	-0.04	0.11	-9999	-10000	0	0
AKT1	-0.012	0.085	-9999	-10000	0	0
BAD	-0.006	0.081	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.034	0.098	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.033	0.099	-9999	-10000	0	0
RAF1	-0.001	0.079	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.023	0.095	-9999	-10000	0	0
YWHAZ	0.012	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.044	0.11	-9999	-0.23	114	114
PIK3CA	0.012	0.001	-9999	-10000	0	0
RPS6KB1	-0.013	0.085	-9999	-10000	0	0
GNB2L1	0.012	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	-0.003	0.071	-9999	-10000	0	0
PXN	0.012	0	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0.018	0	-9999	-10000	0	0
HRAS/GTP	-0.04	0.07	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.015	0.089	-9999	-10000	0	0
IGF-1R heterotetramer	-0.002	0.027	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.032	0.1	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.018	0.091	-9999	-10000	0	0
IGF1R	-0.002	0.027	-9999	-10000	0	0
IGF1	-0.1	0.2	-9999	-0.45	114	114
IRS2/Crk	-0.025	0.094	-9999	-10000	0	0
PI3K	-0.023	0.095	-9999	-10000	0	0
apoptosis	-0.001	0.074	-9999	-10000	0	0
HRAS/GDP	0.008	0.015	-9999	-0.31	1	1
PRKCD	-0.048	0.14	-9999	-0.3	114	114
RAF1/14-3-3 E	0.006	0.073	-9999	-10000	0	0
BAD/14-3-3	0.001	0.078	-9999	-10000	0	0
PRKCZ	-0.012	0.085	-9999	-10000	0	0
Crk/p130 Cas/Paxillin/FAK1	-0.032	0.055	-9999	-10000	0	0
PTPN1	0.012	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.057	0.15	-9999	-0.32	114	114
BCAR1	0.011	0.021	-9999	-0.44	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.025	0.096	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0.012	0	-9999	-10000	0	0
IRS1/NCK2	-0.033	0.098	-9999	-10000	0	0
GRB10	0.012	0	-9999	-10000	0	0
PTPN11	-0.034	0.098	-9999	-10000	0	0
IRS1	-0.044	0.11	-9999	-0.23	114	114
IRS2	-0.034	0.098	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.066	0.14	-9999	-0.32	114	114
GRB2	0.012	0	-9999	-10000	0	0
PDPK1	-0.019	0.089	-9999	-10000	0	0
YWHAE	0.012	0	-9999	-10000	0	0
PRKD1	-0.051	0.15	-9999	-0.48	5	5
SHC1	0.012	0	-9999	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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
SPHK2	0.011	0.021	-9999	-0.44	1	1
SPHK1	-0.04	0.19	-9999	-0.73	32	32
GNAI2	0.012	0	-9999	-10000	0	0
mol:S1P	0	0.068	-9999	-0.24	33	33
GNAO1	-0.11	0.2	-9999	-0.44	125	125
mol:Sphinganine-1-P	-0.021	0.15	-9999	-0.54	33	33
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.021	0.051	-9999	-10000	0	0
GNAI3	0.012	0	-9999	-10000	0	0
G12/G13	0.018	0	-9999	-10000	0	0
S1PR3	0.011	0.035	-9999	-0.73	1	1
S1PR2	0.012	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.002	0.058	-9999	-0.21	33	33
S1PR5	0.001	0.091	-9999	-0.73	7	7
S1PR4	0.002	0.066	-9999	-0.44	10	10
GNAI1	-0.001	0.077	-9999	-0.44	14	14
S1P/S1P5/G12	0.007	0.082	-9999	-0.5	7	7
S1P/S1P3/Gq	0.019	0.057	-9999	-0.41	3	3
S1P/S1P4/Gi	-0.046	0.13	-9999	-0.41	20	20
GNAQ	0.01	0.03	-9999	-0.44	2	2
GNAZ	0.007	0.047	-9999	-0.44	5	5
GNA14	0.01	0.03	-9999	-0.44	2	2
GNA15	0.004	0.077	-9999	-0.73	5	5
GNA12	0.012	0	-9999	-10000	0	0
GNA13	0.012	0	-9999	-10000	0	0
GNA11	0.01	0.03	-9999	-0.44	2	2
ABCC1	0.012	0	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.004	0.086	-9999	-0.52	4	4
CRKL	0.012	0	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
DOCK1	0.012	0	-9999	-10000	0	0
ITGA4	-0.005	0.087	-9999	-0.44	18	18
alpha4/beta7 Integrin/MAdCAM1	-0.1	0.15	-9999	-0.47	26	26
EPO	0	0.069	-9999	-0.73	4	4
alpha4/beta7 Integrin	-0.007	0.094	-9999	-0.33	33	33
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.012	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.006	0.062	-9999	-0.3	18	18
EPO/EPOR (dimer)	0.008	0.059	-9999	-0.55	5	5
lamellipodium assembly	0.032	0.002	-9999	-10000	0	0
PIK3CA	0.012	0.001	-9999	-10000	0	0
PI3K	0.018	0	-9999	-10000	0	0
ARF6	0.012	0	-9999	-10000	0	0
JAK2	0.013	0.066	-9999	-0.54	2	2
PXN	0.012	0	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
MADCAM1	-0.2	0.22	-9999	-0.44	219	219
cell adhesion	-0.1	0.15	-9999	-0.47	26	26
CRKL/CBL	0.018	0	-9999	-10000	0	0
ITGB1	0.012	0	-9999	-10000	0	0
SRC	0.013	0.072	-9999	-0.44	8	8
ITGB7	-0.006	0.089	-9999	-0.44	19	19
RAC1	0.012	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.008	0.08	-9999	-0.48	8	8
p130Cas/Crk/Dock1	0.031	0.064	-9999	-0.36	8	8
VCAM1	0.001	0.069	-9999	-0.44	11	11
RHOA	0.012	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.022	0.049	-9999	-10000	0	0
BCAR1	0.018	0.069	-9999	-0.41	8	8
EPOR	0.011	0.035	-9999	-0.73	1	1
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.012	0	-9999	-10000	0	0
GIT1	0.011	0.021	-9999	-0.44	1	1
Rac1/GTP	0.032	0.002	-9999	-10000	0	0

×

Integrins in angiogenesis

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	0.016	0.03	-9999	-0.43	2	2
alphaV beta3 Integrin	0.004	0.076	-9999	-0.48	2	2
PTK2	0.008	0.1	-9999	-0.44	4	4
IGF1R	0.012	0	-9999	-10000	0	0
PI4KB	0.012	0	-9999	-10000	0	0
MFGE8	0.012	0	-9999	-10000	0	0
SRC	0.012	0	-9999	-10000	0	0
CDKN1B	0.002	0.068	-9999	-0.32	14	14
VEGFA	0.011	0.035	-9999	-0.73	1	1
ILK	0.002	0.068	-9999	-0.32	14	14
ROCK1	0.011	0.021	-9999	-0.44	1	1
AKT1	0.011	0.063	-9999	-0.39	1	1
PTK2B	0.028	0.034	-9999	-0.4	1	1
alphaV/beta3 Integrin/JAM-A	0.004	0.099	-9999	-0.42	16	16
CBL	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.015	0.043	-9999	-0.47	2	2
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.03	0.11	-9999	-10000	0	0
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.027	0.047	-9999	-0.45	1	1
alphaV/beta3 Integrin/Syndecan-1	0.022	0.028	-9999	-10000	0	0
PI4KA	0.012	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.078	0.13	-9999	-0.61	5	5
PI4 Kinase	0.018	0	-9999	-10000	0	0
PIK3CA	0.012	0.001	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.21	0.25	-9999	-0.47	214	214
RPS6KB1	-0.042	0.14	-9999	-0.56	5	5
TLN1	0.012	0	-9999	-10000	0	0
MAPK3	-0.03	0.16	-9999	-0.54	34	34
GPR124	0.011	0.021	-9999	-0.44	1	1
MAPK1	-0.03	0.16	-9999	-0.54	34	34
PXN	0.012	0	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.009	0.096	-9999	-0.47	6	6
cell adhesion	0.024	0.037	-9999	-0.34	2	2
ANGPTL3	0.001	0.049	-9999	-0.73	2	2
VEGFR2 homodimer/VEGFA homodimer/Src	0.023	0.026	-9999	-0.47	1	1
IGF-1R heterotetramer	0.012	0	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
TGFBR2	0.012	0	-9999	-10000	0	0
ITGB3	0.007	0.047	-9999	-0.44	5	5
IGF1	-0.1	0.19	-9999	-0.44	114	114
RAC1	0.012	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	0.021	0.031	-9999	-10000	0	0
apoptosis	0.012	0	-9999	-10000	0	0
CD47	0.012	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	0.022	0.028	-9999	-10000	0	0
VCL	0.012	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.03	0.12	-9999	-0.48	5	5
CSF1	0.01	0.03	-9999	-0.44	2	2
PIK3C2A	0.001	0.07	-9999	-0.33	15	15
PI4 Kinase/Pyk2	-0.024	0.075	-9999	-0.52	1	1
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.028	0.035	-9999	-0.43	1	1
FAK1/Vinculin	0.015	0.085	-9999	-0.37	2	2
alphaV beta3/Integrin/ppsTEM5	0.022	0.031	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
VTN	-0.012	0.13	-9999	-0.73	14	14
BCAR1	0.011	0.021	-9999	-0.44	1	1
FGF2	-0.018	0.11	-9999	-0.44	31	31
F11R	-0.002	0.08	-9999	-0.3	31	31
alphaV/beta3 Integrin/Lactadherin	0.022	0.028	-9999	-10000	0	0
alphaV/beta3 Integrin/TGFBR2	0.022	0.028	-9999	-10000	0	0
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.03	0.02	-9999	-10000	0	0
HSP90AA1	0.012	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	0.021	0.025	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.03	0.16	-9999	-0.65	29	29
alphaV/beta3 Integrin/Pyk2	0.031	0.035	-9999	-0.4	1	1
SDC1	0.012	0	-9999	-10000	0	0
VAV3	0.008	0.071	-9999	-10000	0	0
PTPN11	0.012	0	-9999	-10000	0	0
IRS1	0.012	0	-9999	-10000	0	0
FAK1/Paxillin	0.015	0.085	-9999	-0.37	2	2
cell migration	0.021	0.081	-9999	-10000	0	0
ITGAV	0.012	0	-9999	-10000	0	0
PI3K	-0.025	0.079	-9999	-0.55	1	1
SPP1	-0.34	0.37	-9999	-0.72	218	218
KDR	0.011	0.021	-9999	-0.44	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.012	0	-9999	-10000	0	0
COL4A3	-0.038	0.15	-9999	-0.48	45	45
angiogenesis	-0.026	0.16	-9999	-0.54	34	34
Rac1/GTP	0.014	0.065	-9999	-10000	0	0
EDIL3	-0.074	0.18	-9999	-0.44	88	88
cell proliferation	0.022	0.028	-9999	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.07	0.17	-9999	-0.44	84	84
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.011	0.035	-9999	-0.73	1	1
TCEB1	0.012	0	-9999	-10000	0	0
HIF1A/p53	0.027	0.009	-9999	-10000	0	0
HIF1A	0.02	0.009	-9999	-10000	0	0
COPS5	0.012	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.035	0.023	-9999	-0.4	1	1
FIH (dimer)	0.012	0	-9999	-10000	0	0
CDKN2A	-0.15	0.31	-9999	-0.73	101	101
ARNT/IPAS	-0.041	0.12	-9999	-0.3	85	85
HIF1AN	0.012	0	-9999	-10000	0	0
GNB2L1	0.012	0	-9999	-10000	0	0
HIF1A/ARNT	0.026	0.013	-9999	-10000	0	0
CUL2	0.012	0	-9999	-10000	0	0
OS9	0.012	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.024	0.023	-9999	-0.47	1	1
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.027	0.009	-9999	-10000	0	0
PHD1-3/OS9	0.028	0.03	-9999	-10000	0	0
HIF1A/RACK1/Elongin B/Elongin C	0.036	0.02	-9999	-10000	0	0
VHL	0.012	0	-9999	-10000	0	0
HSP90AA1	0.012	0	-9999	-10000	0	0
HIF1A/JAB1	0.027	0.009	-9999	-10000	0	0
EGLN3	0.006	0.051	-9999	-0.44	6	6
EGLN2	0.011	0.021	-9999	-0.44	1	1
EGLN1	0.012	0	-9999	-10000	0	0
TP53	0.012	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.033	0.015	-9999	-10000	0	0
ARNT	0.011	0.021	-9999	-0.44	1	1
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.011	0.021	-9999	-0.44	1	1
HIF1A/p19ARF	-0.062	0.17	-9999	-0.38	101	101

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.11	0.2	-9999	-0.44	125	125
CDC42/GTP	-0.037	0.12	-9999	-0.39	16	16
PLCG1	-0.038	0.12	-9999	-0.41	16	16
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.012	0	-9999	-10000	0	0
GNAI3	0.012	0	-9999	-10000	0	0
G12/G13	0.018	0	-9999	-10000	0	0
cell migration	-0.037	0.11	-9999	-0.39	16	16
S1PR5	0.001	0.091	-9999	-0.73	7	7
S1PR4	0.002	0.066	-9999	-0.44	10	10
MAPK3	-0.038	0.12	-9999	-0.41	17	17
MAPK1	-0.038	0.12	-9999	-0.41	16	16
S1P/S1P5/Gi	-0.045	0.12	-9999	-0.39	13	13
GNAI1	-0.001	0.077	-9999	-0.44	14	14
CDC42/GDP	0.008	0.015	-9999	-0.31	1	1
S1P/S1P5/G12	0.009	0.061	-9999	-0.48	7	7
RHOA	0.022	0.033	-9999	-10000	0	0
S1P/S1P4/Gi	-0.047	0.13	-9999	-0.44	16	16
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.007	0.047	-9999	-0.44	5	5
S1P/S1P4/G12/G13	0.018	0.036	-9999	-10000	0	0
GNA12	0.012	0	-9999	-10000	0	0
GNA13	0.012	0	-9999	-10000	0	0
CDC42	0.011	0.021	-9999	-0.44	1	1

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.023	0.002	-9999	-10000	0	0
BIRC5	0.011	0.035	-9999	-0.73	1	1
NFKBIA	0.024	0.002	-9999	-10000	0	0
CPEB1	-0.1	0.19	-9999	-0.44	112	112
AKT1	0.024	0.002	-9999	-10000	0	0
NDEL1	0.012	0	-9999	-10000	0	0
Aurora A/BRCA1	0.021	0.001	-9999	-10000	0	0
NDEL1/TACC3	0.028	0.001	-9999	-10000	0	0
GADD45A	0.012	0	-9999	-10000	0	0
GSK3B	0.011	0.001	-9999	-10000	0	0
PAK1/Aurora A	0.023	0.002	-9999	-10000	0	0
MDM2	0.011	0.021	-9999	-0.44	1	1
JUB	-0.23	0.35	-9999	-0.73	151	151
TPX2	0.014	0.053	-9999	-0.55	4	4
TP53	0.024	0.014	-9999	-0.28	1	1
DLG7	0.016	0.002	-9999	-10000	0	0
AURKAIP1	0.012	0	-9999	-10000	0	0
ARHGEF7	0.012	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.029	0.001	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.021	0.001	-9999	-10000	0	0
AURKA	0.02	0.003	-9999	-10000	0	0
AURKB	0.013	0.003	-9999	-10000	0	0
CDC25B	-0.035	0.087	-9999	-0.28	27	27
G2/M transition checkpoint	-0.13	0.21	-9999	-0.43	151	151
mRNA polyadenylation	-0.042	0.1	-9999	-10000	0	0
Aurora A/CPEB	-0.042	0.1	-9999	-10000	0	0
Aurora A/TACC1/TRAP/chTOG	0.036	0.001	-9999	-10000	0	0
BRCA1	0.012	0	-9999	-10000	0	0
centrosome duplication	0.023	0.002	-9999	-10000	0	0
regulation of centrosome cycle	0.027	0.001	-9999	-10000	0	0
spindle assembly	0.035	0.001	-9999	-10000	0	0
TDRD7	0.012	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	0.032	0.02	-9999	-0.38	1	1
CENPA	0.016	0.005	-9999	-10000	0	0
Aurora A/PP2A	0.023	0.002	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.029	0.006	-9999	-10000	0	0
negative regulation of DNA binding	0.024	0.014	-9999	-0.28	1	1
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.018	0.015	-9999	-0.3	1	1
RASA1	0.012	0.001	-9999	-10000	0	0
Ajuba/Aurora A	-0.13	0.21	-9999	-0.43	151	151
mitotic prometaphase	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.003	-9999	-10000	0	0
TACC1	0.012	0	-9999	-10000	0	0
TACC3	0.012	0	-9999	-10000	0	0
Aurora A/Antizyme1	0.029	0.001	-9999	-10000	0	0
Aurora A/RasGAP	0.023	0.002	-9999	-10000	0	0
OAZ1	0.012	0	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.011	0.001	-9999	-10000	0	0
GIT1	0.011	0.021	-9999	-0.44	1	1
GIT1/beta-PIX/PAK1	0.025	0.013	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	0.014	0.053	-9999	-0.55	4	4
PPP2R5D	0.012	0	-9999	-10000	0	0
Aurora A/TPX2	0.024	0.043	-9999	-0.43	4	4
PAK1	0.012	0	-9999	-10000	0	0
CKAP5	0.012	0	-9999	-10000	0	0

×

IL27-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
TGFB1	-0.034	0.1	-10000	0	-0.73	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.003	0.11	0.48	4	-10000	0	4
IL27/IL27R/JAK1	0.012	0.13	-10000	0	-0.77	1	1
TBX21	0.01	0.17	-10000	0	-0.56	18	18
IL12B	0.001	0.07	-10000	0	-0.74	4	4
IL12A	0.004	0.042	-10000	0	-0.35	6	6
IL6ST	0.004	0.064	-10000	0	-0.45	9	9
IL27RA/JAK1	0.021	0.024	-10000	0	-10000	0	0
IL27	-0.014	0.13	-10000	0	-0.73	15	15
TYK2	0.013	0.005	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.14	0.26	-10000	0	-0.8	19	19
T-helper 2 cell differentiation	0.003	0.11	0.48	4	-10000	0	4
T cell proliferation during immune response	0.003	0.11	0.48	4	-10000	0	4
MAPKKK cascade	-0.003	0.11	-10000	0	-0.48	4	4
STAT3	0.012	0	-10000	0	-10000	0	0
STAT2	0.012	0	-10000	0	-10000	0	0
STAT1	0.012	0.035	-10000	0	-0.74	1	1
IL12RB1	-0.008	0.093	-10000	0	-0.45	19	19
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.017	0.15	-10000	0	-0.63	9	9
IL27/IL27R/JAK2/TYK2	-0.003	0.11	-10000	0	-0.49	4	4
positive regulation of T cell mediated cytotoxicity	-0.003	0.11	-10000	0	-0.48	4	4
STAT1 (dimer)	-0.006	0.18	-10000	0	-0.74	5	5
JAK2	0.011	0.037	-10000	0	-0.44	3	3
JAK1	0.012	0.021	-10000	0	-0.44	1	1
STAT2 (dimer)	0.002	0.1	-10000	0	-0.46	4	4
T cell proliferation	-0.085	0.2	-10000	0	-0.57	38	38
IL12/IL12R/TYK2/JAK2	0.003	0.088	-10000	0	-0.45	1	1
IL17A	-0.15	0.25	-10000	0	-0.8	19	19
mast cell activation	0.003	0.11	0.48	4	-10000	0	4
IFNG	-0.002	0.035	-10000	0	-0.089	48	48
T cell differentiation	-0.002	0.005	-10000	0	-0.019	11	11
STAT3 (dimer)	0.002	0.1	-10000	0	-0.67	1	1
STAT5A (dimer)	0.002	0.1	-10000	0	-0.67	1	1
STAT4 (dimer)	-0.009	0.12	-10000	0	-0.44	12	12
STAT4	-0.011	0.1	-10000	0	-0.44	24	24
T cell activation	-0.007	0.003	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	0.018	0.055	-10000	0	-10000	0	0
GATA3	0	0.12	-10000	0	-1.1	5	5
IL18	0.008	0.021	-10000	0	-0.31	2	2
positive regulation of mast cell cytokine production	0.002	0.1	-10000	0	-0.66	1	1
IL27/EBI3	-0.027	0.14	-10000	0	-0.38	53	53
IL27RA	0.011	0.02	-10000	0	-10000	0	0
IL6	-0.16	0.29	-10000	0	-0.76	77	77
STAT5A	0.012	0	-10000	0	-10000	0	0
monocyte differentiation	0	0.002	-10000	0	-10000	0	0
IL2	0.001	0.01	-10000	0	-10000	0	0
IL1B	-0.051	0.17	-10000	0	-0.55	50	50
EBI3	-0.025	0.13	-10000	0	-0.44	39	39
TNF	0.008	0.021	-10000	0	-0.31	2	2

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.018	0.003	-9999	-10000	0	0
SMARCC1	0.003	0.008	-9999	-10000	0	0
REL	0.014	0.007	-9999	-10000	0	0
HDAC7	0.02	0.087	-9999	-0.45	2	2
JUN	0.011	0.005	-9999	-10000	0	0
EP300	0.012	0.001	-9999	-10000	0	0
KAT2B	-0.006	0.087	-9999	-0.44	18	18
KAT5	0.013	0.001	-9999	-10000	0	0
MAPK14	0.014	0.034	-9999	-0.32	4	4
FOXO1	0.011	0.021	-9999	-0.44	1	1
T-DHT/AR	0.019	0.093	-9999	-0.43	4	4
MAP2K6	0.007	0.043	-9999	-0.45	4	4
BRM/BAF57	0.014	0.02	-9999	-0.33	1	1
MAP2K4	0.008	0.037	-9999	-0.44	3	3
SMARCA2	0.009	0.023	-9999	-0.46	1	1
PDE9A	-0.16	0.38	-9999	-0.99	78	78
NCOA2	0.011	0.021	-9999	-0.44	1	1
CEBPA	0.01	0.036	-9999	-0.43	3	3
EHMT2	0.009	0.035	-9999	-0.73	1	1
cell proliferation	0.024	0.11	-9999	-0.43	1	1
NR0B1	-0.006	0.084	-9999	-0.73	6	6
EGR1	0.01	0.021	-9999	-0.44	1	1
RXRs/9cRA	-0.076	0.12	-9999	-10000	0	0
AR/RACK1/Src	0.02	0.06	-9999	-0.35	2	2
AR/GR	-0.004	0.091	-9999	-0.43	7	7
GNB2L1	0.012	0.001	-9999	-10000	0	0
PKN1	0.012	0.001	-9999	-10000	0	0
RCHY1	0.012	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.015	0.029	-9999	-0.31	3	3
T-DHT/AR/TIF2/CARM1	0.026	0.058	-9999	-0.36	2	2
SRC	0.023	0.041	-9999	-10000	0	0
NR3C1	-0.019	0.11	-9999	-0.44	32	32
KLK3	-0.24	0.42	-9999	-1.2	74	74
APPBP2	0.01	0.022	-9999	-0.43	1	1
TRIM24	0.011	0.005	-9999	-10000	0	0
T-DHT/AR/TIP60	0.021	0.055	-9999	-0.38	2	2
TMPRSS2	-0.022	0.093	-9999	-1.1	2	2
RXRG	-0.16	0.22	-9999	-0.44	175	175
mol:9cRA	-0.001	0.002	-9999	-10000	0	0
RXRA	0.011	0.021	-9999	-0.44	1	1
RXRB	0.012	0.001	-9999	-10000	0	0
CARM1	0.012	0.002	-9999	-10000	0	0
NR2C2	0.012	0.001	-9999	-10000	0	0
KLK2	0.015	0.12	-9999	-0.49	19	19
AR	0.008	0.072	-9999	-0.39	5	5
SENP1	0.012	0.001	-9999	-10000	0	0
HSP90AA1	0.012	0	-9999	-10000	0	0
MDM2	0.015	0.024	-9999	-0.44	1	1
SRY	0.004	0.011	-9999	-10000	0	0
GATA2	0.002	0.069	-9999	-0.44	11	11
MYST2	0.013	0.001	-9999	-10000	0	0
HOXB13	-0.25	0.35	-9999	-0.73	162	162
T-DHT/AR/RACK1/Src	0.025	0.056	-9999	-0.36	2	2
positive regulation of transcription	0.002	0.069	-9999	-0.44	11	11
DNAJA1	0.011	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.015	-9999	-0.29	1	1
NCOA1	0.014	0.006	-9999	-10000	0	0
SPDEF	-0.074	0.18	-9999	-0.44	87	87
T-DHT/AR/TIF2	0.023	0.059	-9999	-10000	0	0
T-DHT/AR/Hsp90	0.019	0.055	-9999	-0.38	2	2
GSK3B	0.012	0.003	-9999	-10000	0	0
NR2C1	0.013	0.003	-9999	-10000	0	0
mol:T-DHT	0.018	0.044	-9999	-10000	0	0
SIRT1	0.012	0.001	-9999	-10000	0	0
ZMIZ2	0.016	0.011	-9999	-10000	0	0
POU2F1	0.011	0.037	-9999	-10000	0	0
T-DHT/AR/DAX-1	0.009	0.072	-9999	-0.39	8	8
CREBBP	0.012	0.001	-9999	-10000	0	0
SMARCE1	0.01	0.006	-9999	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.01	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.002	0.08	-10000	0	-0.44	4	4
regulation of S phase of mitotic cell cycle	0.013	0.053	-10000	0	-10000	0	0
GNAO1	-0.11	0.2	-10000	0	-0.44	125	125
HRAS	0.011	0.021	-10000	0	-0.44	1	1
SHBG/T-DHT	0.002	0.046	-10000	0	-0.48	4	4
PELP1	0.012	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
MAP2K1	0.025	0.053	-10000	0	-0.34	2	2
T-DHT/AR	-0.011	0.079	-10000	0	-0.33	26	26
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.008	7	7
GNAI2	0.012	0	-10000	0	-10000	0	0
GNAI3	0.012	0	-10000	0	-10000	0	0
GNAI1	-0.001	0.077	-10000	0	-0.44	14	14
mol:GDP	-0.02	0.082	-10000	0	-0.35	26	26
cell proliferation	0.03	0.074	-10000	0	-0.38	3	3
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
FOS	0.027	0.1	-10000	0	-0.78	7	7
mol:Ca2+	-0.016	0.026	-10000	0	-0.088	27	27
MAPK3	0.027	0.064	-10000	0	-10000	0	0
MAPK1	0.021	0.037	-10000	0	-10000	0	0
PIK3R1	0.012	0	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.005	7	7
cAMP biosynthetic process	0.005	0.047	-10000	0	-0.44	4	4
GNG2	-0.006	0.089	-10000	0	-0.44	19	19
potassium channel inhibitor activity	0	0.001	-10000	0	-0.005	7	7
HRAS/GTP	0.011	0.056	-10000	0	-0.39	2	2
actin cytoskeleton reorganization	0	0.009	-10000	0	-10000	0	0
SRC	0.012	0	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.005	7	7
PI3K	0.017	0	-10000	0	-10000	0	0
apoptosis	-0.029	0.064	0.38	7	-10000	0	7
T-DHT/AR/PELP1	-0.001	0.068	-10000	0	-0.27	26	26
HRAS/GDP	-0.019	0.077	-10000	0	-0.33	26	26
CREB1	0.029	0.067	-10000	0	-0.41	7	7
RAC1-CDC42/GTP	0.024	0.01	-10000	0	-10000	0	0
AR	-0.016	0.11	-10000	0	-0.46	26	26
GNB1	0.012	0	-10000	0	-10000	0	0
RAF1	0.019	0.055	-10000	0	-0.36	2	2
RAC1-CDC42/GDP	0.012	0.081	-10000	0	-0.32	24	24
T-DHT/AR/PELP1/Src	0.008	0.062	-10000	0	-0.43	2	2
MAP2K2	0.025	0.055	-10000	0	-0.34	3	3
T-DHT/AR/PELP1/Src/PI3K	0.013	0.054	-10000	0	-10000	0	0
GNAZ	0.007	0.047	-10000	0	-0.44	5	5
SHBG	0.003	0.069	-10000	0	-0.73	4	4
Gi family/GNB1/GNG2/GDP	-0.067	0.18	-10000	0	-0.5	33	33
mol:T-DHT	0	0	-10000	0	-0.003	7	7
RAC1	0.012	0	-10000	0	-10000	0	0
GNRH1	0.009	0.001	-10000	0	-10000	0	0
Gi family/GTP	-0.041	0.11	-10000	0	-0.38	24	24
CDC42	0.011	0.021	-10000	0	-0.44	1	1

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.004	0.077	-9999	-0.73	5	5
mol:S1P	0.001	0.002	-9999	-10000	0	0
S1P1/S1P/Gi	-0.037	0.11	-9999	-0.36	19	19
GNAO1	-0.11	0.2	-9999	-0.44	125	125
S1P/S1P3/G12/G13	0.025	0.022	-9999	-0.43	1	1
AKT1	-0.002	0.055	-9999	-10000	0	0
AKT3	-0.014	0.16	-9999	-1.2	7	7
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.004	0.077	-9999	-0.73	5	5
GNAI2	0.013	0.003	-9999	-10000	0	0
GNAI3	0.013	0.002	-9999	-10000	0	0
GNAI1	0	0.077	-9999	-0.44	14	14
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.012	0.035	-9999	-0.73	1	1
S1PR2	0.012	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.036	0.12	-9999	-0.41	19	19
MAPK3	-0.029	0.12	-9999	-0.39	20	20
MAPK1	-0.028	0.12	-9999	-0.39	19	19
JAK2	-0.028	0.12	-9999	-0.4	19	19
CXCR4	-0.028	0.12	-9999	-0.39	19	19
FLT1	0.015	0.002	-9999	-10000	0	0
RhoA/GDP	0.009	0	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
SRC	-0.028	0.12	-9999	-0.39	19	19
S1P/S1P3/Gi	-0.036	0.13	-9999	-0.41	19	19
RAC1	0.012	0	-9999	-10000	0	0
RhoA/GTP	-0.027	0.12	-9999	-0.37	19	19
VEGFA	0.013	0.035	-9999	-0.73	1	1
S1P/S1P2/Gi	-0.037	0.12	-9999	-0.37	19	19
VEGFR1 homodimer/VEGFA homodimer	0.023	0.028	-9999	-0.55	1	1
RHOA	0.012	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.021	0.044	-9999	-0.53	1	1
GNAQ	0.01	0.03	-9999	-0.44	2	2
GNAZ	0.008	0.047	-9999	-0.44	5	5
G12/G13	0.018	0	-9999	-10000	0	0
GNA14	0.01	0.03	-9999	-0.44	2	2
GNA15	0.004	0.077	-9999	-0.73	5	5
GNA12	0.012	0	-9999	-10000	0	0
GNA13	0.012	0	-9999	-10000	0	0
GNA11	0.01	0.03	-9999	-0.44	2	2
Rac1/GTP	-0.027	0.12	-9999	-0.37	19	19

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0	0.04	-9999	-0.44	2	2
SVIL	0.003	0.024	-9999	-10000	0	0
ZNF318	0.035	0.057	-9999	-10000	0	0
JMJD2C	0.003	0.026	-9999	-0.11	19	19
T-DHT/AR/Ubc9	0.008	0.073	-9999	-0.42	4	4
CARM1	0.011	0.004	-9999	-10000	0	0
PRDX1	0.014	0.004	-9999	-10000	0	0
PELP1	0.016	0.01	-9999	-10000	0	0
CTNNB1	0.005	0.02	-9999	-10000	0	0
AKT1	0.019	0.016	-9999	-10000	0	0
PTK2B	0.004	0.027	-9999	-0.44	1	1
MED1	0.018	0.04	-9999	-0.73	1	1
MAK	0.008	0.15	-9999	-0.73	16	16
response to oxidative stress	0.002	0.005	-9999	-10000	0	0
HIP1	0.002	0.031	-9999	-0.44	1	1
GSN	-0.008	0.072	-9999	-0.46	10	10
NCOA2	0.01	0.021	-9999	-0.44	1	1
NCOA6	0.003	0.023	-9999	-10000	0	0
DNA-PK	0.046	0.054	-9999	-10000	0	0
NCOA4	0.01	0.021	-9999	-0.44	1	1
PIAS3	0.005	0.02	-9999	-10000	0	0
cell proliferation	0.007	0.091	-9999	-0.37	16	16
XRCC5	0.017	0.013	-9999	-10000	0	0
UBE3A	-0.004	0.043	-9999	-0.44	1	1
T-DHT/AR/SNURF	-0.021	0.12	-9999	-0.3	58	58
FHL2	0.044	0.055	-9999	-10000	0	0
RANBP9	0.002	0.031	-9999	-0.44	1	1
JMJD1A	0.007	0.025	-9999	-0.13	13	13
CDK6	0.013	0.003	-9999	-10000	0	0
TGFB1I1	0.003	0.024	-9999	-10000	0	0
T-DHT/AR/CyclinD1	-0.002	0.083	-9999	-0.38	11	11
XRCC6	0.017	0.013	-9999	-10000	0	0
T-DHT/AR	0.022	0.086	-9999	-0.46	4	4
CTDSP1	0.009	0.008	-9999	-10000	0	0
CTDSP2	0.028	0.039	-9999	-10000	0	0
BRCA1	0.003	0.024	-9999	-10000	0	0
TCF4	0.023	0.036	-9999	-0.44	1	1
CDKN2A	-0.14	0.31	-9999	-0.72	101	101
SRF	0.026	0.018	-9999	-10000	0	0
NKX3-1	0	0.13	-9999	-0.78	11	11
KLK3	-0.19	0.5	-9999	-1.3	73	73
TMF1	0.01	0.021	-9999	-0.44	1	1
HNRNPA1	0.021	0.021	-9999	-10000	0	0
AOF2	-0.01	0.025	-9999	-0.068	72	72
APPL1	0.032	0.042	-9999	-10000	0	0
T-DHT/AR/Caspase 8	0.017	0.079	-9999	-0.42	4	4
AR	-0.013	0.11	-9999	-0.46	26	26
UBA3	0.009	0.008	-9999	-10000	0	0
PATZ1	0.021	0.021	-9999	-10000	0	0
PAWR	0.011	0.005	-9999	-10000	0	0
PRKDC	0.017	0.013	-9999	-10000	0	0
PA2G4	0.022	0.026	-9999	-10000	0	0
UBE2I	0.012	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.015	0.07	-9999	-0.38	4	4
RPS6KA3	0.002	0.027	-9999	-10000	0	0
T-DHT/AR/ARA70	0.002	0.073	-9999	-0.27	26	26
LATS2	0.021	0.021	-9999	-10000	0	0
T-DHT/AR/PRX1	0.021	0.077	-9999	-0.38	4	4
Cyclin D3/CDK11 p58	0.011	0.005	-9999	-10000	0	0
VAV3	-0.04	0.14	-9999	-0.44	46	46
KLK2	-0.01	0.12	-9999	-0.58	19	19
CASP8	0.016	0.009	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.009	0.069	-9999	-0.38	4	4
TMPRSS2	0.012	0.074	-9999	-0.84	2	2
CCND1	0.003	0.061	-9999	-0.73	3	3
PIAS1	-0.003	0.038	-9999	-10000	0	0
mol:T-DHT	0.003	0.016	-9999	-0.059	26	26
CDC2L1	0.001	0.002	-9999	-10000	0	0
PIAS4	-0.01	0.055	-9999	-10000	0	0
T-DHT/AR/CDK6	0.012	0.075	-9999	-0.32	9	9
CMTM2	-0.015	0.14	-9999	-0.73	18	18
SNURF	-0.036	0.14	-9999	-0.46	44	44
ZMIZ1	0.015	0.015	-9999	-10000	0	0
CCND3	0.013	0.002	-9999	-10000	0	0
TGIF1	0.021	0.021	-9999	-10000	0	0
FKBP4	0.002	0.041	-9999	-0.73	1	1

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0	0.092	0.49	15	-10000	0	15
KIRREL	0.006	0.055	-10000	0	-0.5	5	5
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0	0.092	-10000	0	-0.49	15	15
PLCG1	0.012	0	-10000	0	-10000	0	0
ARRB2	0.012	0	-10000	0	-10000	0	0
WASL	0.012	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.002	0.093	-10000	0	-0.43	14	14
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.018	0.053	-10000	0	-0.48	1	1
FYN	0.005	0.074	-10000	0	-0.38	14	14
mol:Ca2+	0.008	0.082	-10000	0	-0.43	14	14
mol:DAG	0.009	0.083	-10000	0	-0.43	14	14
NPHS2	-0.002	0.07	-10000	0	-0.74	4	4
mol:IP3	0.009	0.083	-10000	0	-0.43	14	14
regulation of endocytosis	0.013	0.071	-10000	0	-0.36	14	14
Nephrin/NEPH1/podocin/Cholesterol	0.001	0.083	-10000	0	-0.44	14	14
establishment of cell polarity	0	0.092	-10000	0	-0.49	15	15
Nephrin/NEPH1/podocin/NCK1-2	0.017	0.077	-10000	0	-0.39	14	14
Nephrin/NEPH1/beta Arrestin2	0.014	0.072	-10000	0	-0.36	14	14
NPHS1	-0.006	0.11	-10000	0	-0.73	10	10
Nephrin/NEPH1/podocin	0.006	0.075	-10000	0	-0.39	14	14
TJP1	0.012	0	-10000	0	-10000	0	0
NCK1	0.012	0	-10000	0	-10000	0	0
NCK2	0.012	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.009	0.083	-10000	0	-0.43	14	14
CD2AP	0	0.075	-10000	0	-0.44	13	13
Nephrin/NEPH1/podocin/GRB2	0.009	0.083	-10000	0	-0.43	14	14
GRB2	0.012	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.006	0.093	-10000	0	-0.4	16	16
cytoskeleton organization	0.021	0.067	-10000	0	-0.64	1	1
Nephrin/NEPH1	0.002	0.068	-10000	0	-0.41	11	11
Nephrin/NEPH1/ZO-1	0.01	0.076	-10000	0	-0.45	11	11

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.024	0	-9999	-10000	0	0
SNTA1	0.011	0.021	-9999	-0.44	1	1
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.023	0.013	-9999	-10000	0	0
MAPK12	0.017	0.062	-9999	-0.5	6	6
CCND1	0.015	0.029	-9999	-0.2	5	5
p38 gamma/SNTA1	0.022	0.06	-9999	-0.46	6	6
MAP2K3	0.012	0	-9999	-10000	0	0
PKN1	0.012	0	-9999	-10000	0	0
G2/M transition checkpoint	0.017	0.062	-9999	-0.49	6	6
MAP2K6	0.018	0.024	-9999	-0.24	4	4
MAPT	-0.039	0.12	-9999	-0.27	98	98
MAPK13	0.019	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.015	0	-9999	-10000	0	0

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.063	0.18	-9999	-0.6	36	36
RAD9A	0.012	0	-9999	-10000	0	0
AP1	0.014	0.04	-9999	-10000	0	0
IFNAR2	0.013	0.004	-9999	-10000	0	0
AKT1	-0.003	0.056	-9999	-10000	0	0
ER alpha/Oestrogen	-0.02	0.092	-9999	-0.31	42	42
NFX1/SIN3/HDAC complex	0.038	0.013	-9999	-10000	0	0
EGF	-0.089	0.21	-9999	-0.49	91	91
SMG5	0.012	0	-9999	-10000	0	0
SMG6	0.012	0	-9999	-10000	0	0
SP3/HDAC2	0.019	0.008	-9999	-10000	0	0
TERT/c-Abl	-0.053	0.17	-9999	-0.59	26	26
SAP18	0.012	0.001	-9999	-10000	0	0
MRN complex	0.025	0.013	-9999	-10000	0	0
WT1	-0.36	0.37	-9999	-0.73	228	228
WRN	0.011	0.021	-9999	-0.44	1	1
SP1	0.013	0.006	-9999	-10000	0	0
SP3	0.012	0.003	-9999	-10000	0	0
TERF2IP	0.012	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.061	0.15	-9999	-0.67	7	7
Mad/Max	0.017	0.022	-9999	-0.3	2	2
TERT	-0.065	0.19	-9999	-0.62	36	36
CCND1	-0.052	0.17	-9999	-0.81	5	5
MAX	0.012	0.003	-9999	-10000	0	0
RBBP7	0.012	0.001	-9999	-10000	0	0
RBBP4	0.012	0.001	-9999	-10000	0	0
TERF2	0.011	0	-9999	-10000	0	0
PTGES3	0.012	0	-9999	-10000	0	0
SIN3A	0.012	0.001	-9999	-10000	0	0
Telomerase/911	0.024	0.028	-9999	-10000	0	0
CDKN1B	-0.019	0.15	-9999	-0.46	47	47
RAD1	0.011	0.035	-9999	-0.73	1	1
XRCC5	0.012	0	-9999	-10000	0	0
XRCC6	0.012	0	-9999	-10000	0	0
SAP30	0.012	0.001	-9999	-10000	0	0
TRF2/PARP2	0.018	0	-9999	-10000	0	0
UBE3A	0.011	0.021	-9999	-0.44	1	1
JUN	0.012	0.003	-9999	-10000	0	0
E6	0	0.003	-9999	-10000	0	0
HPV-16 E6/E6AP	0.009	0.016	-9999	-0.31	1	1
FOS	0.005	0.055	-9999	-0.44	7	7
IFN-gamma/IRF1	-0.033	0.17	-9999	-0.54	47	47
PARP2	0.012	0	-9999	-10000	0	0
BLM	0.012	0	-9999	-10000	0	0
Telomerase	0.002	0.055	-9999	-0.35	2	2
IRF1	0.016	0.003	-9999	-10000	0	0
ESR1	-0.029	0.13	-9999	-0.44	42	42
KU/TER	0.018	0	-9999	-10000	0	0
ATM/TRF2	0.019	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.042	0.016	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.042	0.016	-9999	-10000	0	0
HDAC1	0.012	0.001	-9999	-10000	0	0
HDAC2	0.013	0.006	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.016	0.037	-9999	-0.36	4	4
ABL1	0.012	0	-9999	-10000	0	0
MXD1	0.01	0.03	-9999	-0.44	2	2
MRE11A	0.012	0.001	-9999	-10000	0	0
HUS1	0.012	0	-9999	-10000	0	0
RPS6KB1	0.011	0.021	-9999	-0.44	1	1
TERT/NF kappa B1/14-3-3	-0.037	0.17	-9999	-0.65	12	12
NR2F2	0.012	0.006	-9999	-10000	0	0
MAPK3	0.012	0.017	-9999	-0.32	1	1
MAPK1	0.012	0.006	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.011	0.035	-9999	-0.73	1	1
NFKB1	0.012	0	-9999	-10000	0	0
HNRNPC	0.012	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	0.011	0.021	-9999	-0.44	1	1
EGFR	0.011	0.021	-9999	-0.44	1	1
mol:Oestrogen	0	0.002	-9999	-10000	0	0
EGF/EGFR	-0.056	0.15	-9999	-0.35	92	92
MYC	0.001	0.091	-9999	-0.73	7	7
IL2	0.004	0.009	-9999	-10000	0	0
KU	0.018	0	-9999	-10000	0	0
RAD50	0.012	0	-9999	-10000	0	0
HSP90AA1	0.012	0	-9999	-10000	0	0
TGFB1	0.011	0.035	-9999	-0.73	1	1
TRF2/BLM	0.018	0	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.048	0.17	-9999	-0.6	23	23
SP1/HDAC2	0.02	0.011	-9999	-10000	0	0
PINX1	0.012	0	-9999	-10000	0	0
Telomerase/EST1A	-0.061	0.15	-9999	-0.65	8	8
Smad3/Myc	0.013	0.069	-9999	-0.47	8	8
911 complex	0.024	0.023	-9999	-0.47	1	1
IFNG	-0.061	0.22	-9999	-0.72	47	47
Telomerase/PinX1	-0.061	0.15	-9999	-0.65	8	8
Telomerase/AKT1/mTOR/p70S6K	0.008	0.05	-9999	-10000	0	0
SIN3B	0.012	0.001	-9999	-10000	0	0
YWHAE	0.012	0	-9999	-10000	0	0
Telomerase/EST1B	-0.061	0.15	-9999	-0.65	8	8
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0.035	0.011	-9999	-10000	0	0
TRF2/WRN	0.017	0.014	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.061	0.15	-9999	-0.65	8	8
E2F1	-0.003	0.11	-9999	-0.73	10	10
ZNFX1	0.012	0.001	-9999	-10000	0	0
PIF1	-0.004	0.11	-9999	-0.73	10	10
NCL	0.012	0	-9999	-10000	0	0
DKC1	0.012	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.003	0.08	-10000	0	-0.68	6	6
ANTXR2	0.011	0.021	-10000	0	-0.44	1	1
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.001	0.01	-10000	0	-0.079	7	7
monocyte activation	0.003	0.066	-10000	0	-0.38	13	13
MAP2K2	0.009	0.034	-10000	0	-0.71	1	1
MAP2K1	-0.001	0.008	-10000	0	-10000	0	0
MAP2K7	-0.002	0.013	-10000	0	-0.22	1	1
MAP2K6	-0.003	0.022	-10000	0	-0.22	4	4
CYAA	0.006	0.047	-10000	0	-0.36	7	7
MAP2K4	-0.002	0.019	-10000	0	-0.22	3	3
IL1B	-0.033	0.13	-10000	0	-0.39	52	52
Channel	0.01	0.05	-10000	0	-0.38	7	7
NLRP1	-0.004	0.032	-10000	0	-0.32	4	4
CALM1	0.012	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.01	0.013	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.001	0.01	0.079	7	-10000	0	7
MAPK3	-0.002	0.013	-10000	0	-0.22	1	1
MAPK1	-0.001	0.008	-10000	0	-10000	0	0
PGR	-0.045	0.088	-10000	0	-0.22	92	92
PA/Cellular Receptors	0.01	0.054	-10000	0	-0.41	7	7
apoptosis	-0.001	0.01	-10000	0	-0.079	7	7
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.01	0.045	-10000	0	-0.34	7	7
macrophage activation	0.014	0.014	-10000	0	-10000	0	0
TNF	0.01	0.03	-10000	0	-0.44	2	2
VCAM1	0.003	0.066	-10000	0	-0.38	13	13
platelet activation	0.01	0.013	-10000	0	-10000	0	0
MAPKKK cascade	-0.011	0.014	0.13	1	-10000	0	1
IL18	0.011	0.023	-10000	0	-0.2	4	4
negative regulation of macrophage activation	-0.001	0.01	-10000	0	-0.079	7	7
LEF	-0.001	0.01	-10000	0	-0.08	7	7
CASP1	-0.003	0.018	-10000	0	-0.16	4	4
mol:cAMP	-0.001	0.012	-10000	0	-10000	0	0
necrosis	-0.001	0.01	-10000	0	-0.079	7	7
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.01	0.047	-10000	0	-0.36	7	7
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.012	0	-10000	0	-10000	0	0
NFATC1	0.045	0.032	-10000	0	-10000	0	0
NFATC2	0.031	0.025	-10000	0	-10000	0	0
NFATC3	0.021	0.003	-10000	0	-10000	0	0
YWHAE	0.012	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.067	0.12	-10000	0	-0.35	37	37
Exportin 1/Ran/NUP214	0.025	0.003	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.077	0.1	-10000	0	-0.48	9	9
BCL2/BAX	0.003	0.068	-10000	0	-0.3	22	22
CaM/Ca2+/Calcineurin A alpha-beta B1	0.01	0.003	-10000	0	-10000	0	0
CaM/Ca2+	0.01	0.003	-10000	0	-10000	0	0
BAX	0.012	0	-10000	0	-10000	0	0
MAPK14	0.012	0.002	-10000	0	-10000	0	0
BAD	0.011	0.021	-10000	0	-0.44	1	1
CABIN1/MEF2D	-0.057	0.11	-10000	0	-0.33	37	37
Calcineurin A alpha-beta B1/BCL2	-0.009	0.096	-10000	0	-0.44	22	22
FKBP8	0.011	0.021	-10000	0	-0.44	1	1
activation-induced cell death of T cells	0.057	0.11	0.32	37	-10000	0	37
KPNB1	0.012	0	-10000	0	-10000	0	0
KPNA2	0.011	0.035	-10000	0	-0.73	1	1
XPO1	0.012	0	-10000	0	-10000	0	0
SFN	0.01	0.03	-10000	0	-0.44	2	2
MAP3K8	0.012	0.002	-10000	0	-10000	0	0
NFAT4/CK1 alpha	0.03	0.011	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.051	0.049	-10000	0	-10000	0	0
CABIN1	-0.068	0.12	-10000	0	-0.35	37	37
CALM1	0.013	0.001	-10000	0	-10000	0	0
RAN	0.012	0	-10000	0	-10000	0	0
MAP3K1	0.011	0.021	-10000	0	-0.44	1	1
CAMK4	-0.016	0.11	-10000	0	-0.44	29	29
mol:Ca2+	0.001	0.002	-10000	0	-10000	0	0
MAPK3	0.011	0.021	-10000	0	-0.44	1	1
YWHAH	0.012	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.002	0.071	-10000	0	-0.3	24	24
YWHAB	0.012	0	-10000	0	-10000	0	0
MAPK8	0.013	0.002	-10000	0	-10000	0	0
MAPK9	0.012	0	-10000	0	-10000	0	0
YWHAG	0.012	0	-10000	0	-10000	0	0
FKBP1A	0.012	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.06	0.03	-10000	0	-10000	0	0
PRKCH	0.011	0.021	-10000	0	-0.44	1	1
CABIN1/Cbp/p300	0.019	0.004	-10000	0	-10000	0	0
CASP3	0.012	0.002	-10000	0	-10000	0	0
PIM1	0.012	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.009	0.001	-10000	0	-10000	0	0
apoptosis	-0.004	0.019	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.036	0.021	-10000	0	-0.39	1	1
PRKCB	-0.09	0.19	-10000	0	-0.44	104	104
PRKCE	0.012	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.026	0.002	-10000	0	-10000	0	0
BAD/BCL-XL	0.018	0.015	-10000	0	-0.3	1	1
PRKCD	0.012	0	-10000	0	-10000	0	0
NUP214	0.012	0	-10000	0	-10000	0	0
PRKCZ	0.013	0.002	-10000	0	-10000	0	0
PRKCA	0.012	0	-10000	0	-10000	0	0
PRKCG	-0.24	0.35	-10000	0	-0.73	154	154
PRKCQ	0.006	0.051	-10000	0	-0.44	6	6
FKBP38/BCL2	0.002	0.07	-10000	0	-0.3	23	23
EP300	0.013	0.002	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.012	0	-10000	0	-10000	0	0
NFATc/JNK1	0.05	0.031	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0.017	0.013	-10000	0	-0.26	1	1
FKBP12/FK506	0.009	0	-10000	0	-10000	0	0
CSNK1A1	0.017	0.003	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0	0.066	-10000	0	-0.25	29	29
NFATc/ERK1	0.05	0.032	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.077	0.1	-10000	0	-0.48	9	9
NR4A1	0.045	0.086	-10000	0	-0.58	8	8
GSK3B	0.013	0.002	-10000	0	-10000	0	0
positive T cell selection	0.021	0.003	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.003	0.014	-10000	0	-10000	0	0
RCH1/ KPNB1	0.017	0.027	-10000	0	-0.55	1	1
YWHAQ	0.012	0	-10000	0	-10000	0	0
PRKACA	0.012	0.002	-10000	0	-10000	0	0
AKAP5	-0.011	0.1	-10000	0	-0.44	24	24
MEF2D	0.013	0.002	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.012	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.05	0.031	-10000	0	-10000	0	0
CREBBP	0.013	0.002	-10000	0	-10000	0	0
BCL2	-0.009	0.096	-10000	0	-0.44	22	22

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0	0.02	-10000	0	-10000	0	0
DAPP1	-0.041	0.12	-10000	0	-0.41	19	19
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.056	0.15	-10000	0	-0.47	23	23
mol:DAG	-0.012	0.086	-10000	0	-0.26	11	11
HRAS	0.012	0.021	-10000	0	-0.44	1	1
RAP1A	0.013	0.001	-10000	0	-10000	0	0
ARF5/GDP	0.005	0.1	-10000	0	-0.41	17	17
PLCG2	-0.032	0.13	-10000	0	-0.44	45	45
PLCG1	0.012	0	-10000	0	-10000	0	0
ARF5	0.012	0	-10000	0	-10000	0	0
mol:GTP	0	0.02	-10000	0	-10000	0	0
ARF1/GTP	0.032	0.02	-10000	0	-10000	0	0
RHOA	0.012	0	-10000	0	-10000	0	0
YES1	0.011	0.021	-10000	0	-0.44	1	1
RAP1A/GTP	0.023	0.02	-10000	0	-10000	0	0
ADAP1	-0.001	0.025	-10000	0	-0.38	1	1
ARAP3	0	0.02	-10000	0	-10000	0	0
INPPL1	0.012	0	-10000	0	-10000	0	0
PREX1	0.01	0.03	-10000	0	-0.44	2	2
ARHGEF6	0.001	0.069	-10000	0	-0.44	11	11
ARHGEF7	0.012	0	-10000	0	-10000	0	0
ARF1	0.012	0	-10000	0	-10000	0	0
NRAS	0.011	0.03	-10000	0	-0.44	2	2
FYN	0.012	0	-10000	0	-10000	0	0
ARF6	0.012	0	-10000	0	-10000	0	0
FGR	0.008	0.05	-10000	0	-0.51	4	4
mol:Ca2+	0	0.048	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.03	0.13	-10000	0	-0.44	43	43
ZAP70	-0.001	0.079	-10000	0	-0.46	13	13
mol:IP3	-0.004	0.065	-10000	0	-10000	0	0
LYN	0.012	0	-10000	0	-10000	0	0
ARF1/GDP	0.005	0.1	-10000	0	-0.41	17	17
RhoA/GDP	0.028	0.05	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.025	0	-10000	0	-10000	0	0
BLNK	0.005	0.055	-10000	0	-0.44	7	7
actin cytoskeleton reorganization	0.03	0.073	-10000	0	-0.39	5	5
SRC	0.012	0	-10000	0	-10000	0	0
PLEKHA2	0.023	0.013	-10000	0	-10000	0	0
RAC1	0.012	0	-10000	0	-10000	0	0
PTEN	0.007	0.028	-10000	0	-0.41	2	2
HSP90AA1	0.012	0	-10000	0	-10000	0	0
ARF6/GTP	0	0.02	-10000	0	-10000	0	0
RhoA/GTP	0.028	0.02	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.04	0.12	-10000	0	-0.37	23	23
BLK	-0.16	0.22	-10000	0	-0.44	173	173
PDPK1	0.012	0	-10000	0	-10000	0	0
CYTH1	0	0.019	-10000	0	-10000	0	0
HCK	0.001	0.072	-10000	0	-0.44	12	12
CYTH3	0	0.019	-10000	0	-10000	0	0
CYTH2	0	0.019	-10000	0	-10000	0	0
KRAS	0.013	0.001	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.017	0.093	-10000	0	-0.4	21	21
SGK1	-0.02	0.093	-10000	0	-0.44	21	21
INPP5D	0.011	0.021	-10000	0	-0.44	1	1
mol:GDP	-0.002	0.1	-10000	0	-0.44	17	17
SOS1	0.012	0	-10000	0	-10000	0	0
SYK	0.012	0	-10000	0	-10000	0	0
ARF6/GDP	0.027	0.05	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0.022	0.24	2	-10000	0	2
ARAP3/RAP1A/GTP	0.023	0.021	-10000	0	-10000	0	0
VAV1	-0.009	0.096	-10000	0	-0.44	22	22
mol:PI-3-4-P2	0.019	0.015	-10000	0	-0.3	1	1
RAS family/GTP/PI3K Class I	0.026	0.018	-10000	0	-10000	0	0
PLEKHA1	0.023	0.013	-10000	0	-10000	0	0
Rac1/GDP	0.005	0.1	-10000	0	-0.41	17	17
LAT	0.009	0.046	-10000	0	-0.53	3	3
Rac1/GTP	-0.007	0.13	-10000	0	-0.53	18	18
ITK	-0.008	0.039	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.022	0.11	-10000	0	-0.34	19	19
LCK	-0.001	0.096	-10000	0	-0.66	9	9
BTK	-0.024	0.063	-10000	0	-10000	0	0

×

IFN-gamma 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.006	0.12	-9999	-0.35	41	41
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.012	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.02	0.11	-9999	-0.64	1	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.015	0.037	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.022	0.047	-9999	-10000	0	0
CaM/Ca2+	-0.004	0.11	-9999	-10000	0	0
RAP1A	0.012	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.001	0.12	-9999	-0.72	1	1
AKT1	0.009	0.1	-9999	-10000	0	0
MAP2K1	0.004	0.11	-9999	-10000	0	0
MAP3K11	-0.004	0.11	-9999	-10000	0	0
IFNGR1	0.009	0.012	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.026	0.13	-9999	-0.49	16	16
Rap1/GTP	-0.027	0.075	-9999	-10000	0	0
CRKL/C3G	0.018	0.015	-9999	-0.3	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.008	0.13	-9999	-0.38	47	47
CEBPB	0.017	0.13	-9999	-0.51	2	2
STAT3	0.012	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.011	0.15	-9999	-0.77	6	6
STAT1	-0.003	0.12	-9999	-0.72	1	1
CALM1	0.012	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.064	0.22	-9999	-0.72	47	47
PIK3CA	0.012	0.001	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	0.005	0.11	-9999	-0.68	1	1
CEBPB/PTGES2/Cbp/p300	-0.028	0.067	-9999	-0.34	1	1
mol:Ca2+	-0.008	0.12	-9999	-0.35	41	41
MAPK3	0.012	0.11	-9999	-0.9	1	1
STAT1 (dimer)	-0.029	0.062	-9999	-10000	0	0
MAPK1	0.014	0.1	-9999	-10000	0	0
JAK2	0.007	0.038	-9999	-0.44	3	3
PIK3R1	0.012	0	-9999	-10000	0	0
JAK1	0.008	0.024	-9999	-0.43	1	1
CAMK2D	0.012	0	-9999	-10000	0	0
DAPK1	0.012	0.15	-9999	-0.58	22	22
SMAD7	0.027	0.046	-9999	-0.24	1	1
CBL/CRKL/C3G	0.009	0.1	-9999	-10000	0	0
PI3K	-0.033	0.095	-9999	-10000	0	0
IFNG	-0.064	0.22	-9999	-0.72	47	47
apoptosis	0.009	0.11	-9999	-0.43	22	22
CAMK2G	0.012	0	-9999	-10000	0	0
STAT3 (dimer)	0.012	0	-9999	-10000	0	0
CAMK2A	-0.023	0.12	-9999	-0.44	35	35
CAMK2B	-0.027	0.13	-9999	-0.48	35	35
FRAP1	0.008	0.095	-9999	-10000	0	0
PRKCD	0.009	0.1	-9999	-10000	0	0
RAP1B	0.012	0	-9999	-10000	0	0
negative regulation of cell growth	-0.022	0.047	-9999	-10000	0	0
PTPN2	0.012	0.001	-9999	-10000	0	0
EP300	0.013	0	-9999	-10000	0	0
IRF1	0.025	0.1	-9999	-0.44	7	7
STAT1 (dimer)/PIASy	0.003	0.11	-9999	-0.68	1	1
SOCS1	-0.009	0.083	-9999	-0.53	11	11
mol:GDP	0.006	0.1	-9999	-10000	0	0
CASP1	0.027	0.046	-9999	-0.28	1	1
PTGES2	0.012	0	-9999	-10000	0	0
IRF9	0.032	0.046	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.033	0.093	-9999	-10000	0	0
RAP1/GDP	-0.027	0.076	-9999	-10000	0	0
CBL	-0.003	0.11	-9999	-10000	0	0
MAP3K1	-0.003	0.11	-9999	-10000	0	0
PIAS1	0.012	0	-9999	-10000	0	0
PIAS4	0.012	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.022	0.047	-9999	-10000	0	0
PTPN11	-0.01	0.12	-9999	-0.35	41	41
CREBBP	0.013	0	-9999	-10000	0	0
RAPGEF1	0.011	0.021	-9999	-0.44	1	1

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.12	0.41	-9999	-1.2	55	55
PLK1	0.048	0.13	-9999	-0.87	2	2
CDKN1B	0.075	0.085	-9999	-10000	0	0
FOXO3	0.045	0.14	-9999	-0.64	6	6
KAT2B	0.004	0.089	-9999	-0.43	18	18
FOXO1/SIRT1	-0.032	0.13	-9999	-0.37	55	55
CAT	0.049	0.13	-9999	-0.96	1	1
CTNNB1	0.012	0	-9999	-10000	0	0
AKT1	0.017	0.019	-9999	-10000	0	0
FOXO1	-0.02	0.14	-9999	-0.41	55	55
MAPK10	-0.001	0.081	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
FOXO4	0.065	0.055	-9999	-10000	0	0
response to oxidative stress	0.005	0.021	-9999	-10000	0	0
FOXO3A/SIRT1	-0.007	0.1	-9999	-0.58	6	6
XPO1	0.013	0	-9999	-10000	0	0
EP300	0.007	0.019	-9999	-10000	0	0
BCL2L11	0.025	0.027	-9999	-10000	0	0
FOXO1/SKP2	-0.013	0.13	-9999	-0.37	55	55
mol:GDP	0.005	0.021	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
GADD45A	0.079	0.059	-9999	-10000	0	0
YWHAQ	0.012	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.051	0.039	-9999	-10000	0	0
MST1	-0.091	0.27	-9999	-0.72	70	70
CSNK1D	0.012	0	-9999	-10000	0	0
CSNK1E	0.012	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.049	0.018	-9999	-10000	0	0
YWHAB	0.012	0	-9999	-10000	0	0
MAPK8	0.032	0.008	-9999	-10000	0	0
MAPK9	0.032	0.008	-9999	-10000	0	0
YWHAG	0.012	0	-9999	-10000	0	0
YWHAE	0.012	0	-9999	-10000	0	0
YWHAZ	0.012	0	-9999	-10000	0	0
SIRT1	0.014	0.015	-9999	-10000	0	0
SOD2	0.074	0.097	-9999	-10000	0	0
RBL2	0.062	0.099	-9999	-0.62	1	1
RAL/GDP	0.025	0.013	-9999	-10000	0	0
CHUK	0.022	0.008	-9999	-10000	0	0
Ran/GTP	0.013	0	-9999	-10000	0	0
CSNK1G2	0.011	0.021	-9999	-0.44	1	1
RAL/GTP	0.032	0.012	-9999	-10000	0	0
CSNK1G1	0.011	0.021	-9999	-0.44	1	1
FASLG	-0.056	0.33	-9999	-1.3	30	30
SKP2	0.012	0	-9999	-10000	0	0
USP7	0.014	0	-9999	-10000	0	0
IKBKB	0.022	0.008	-9999	-10000	0	0
CCNB1	0.049	0.13	-9999	-0.96	1	1
FOXO1-3a-4/beta catenin	0.079	0.1	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.013	0.13	-9999	-0.37	55	55
CSNK1A1	0.012	0	-9999	-10000	0	0
SGK1	0.001	0.095	-9999	-0.43	21	21
CSNK1G3	0.012	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.023	0	-9999	-10000	0	0
ZFAND5	0.067	0.05	-9999	-10000	0	0
SFN	0.01	0.03	-9999	-0.44	2	2
CDK2	0.002	0.029	-9999	-10000	0	0
FOXO3A/14-3-3	0.053	0.03	-9999	-10000	0	0
CREBBP	0.002	0.029	-9999	-10000	0	0
FBXO32	0.047	0.14	-9999	-1.5	1	1
BCL6	0.062	0.099	-9999	-0.62	1	1
RALB	0.013	0	-9999	-10000	0	0
RALA	0.013	0	-9999	-10000	0	0
YWHAH	0.012	0	-9999	-10000	0	0

×

PDGFR-beta signaling pathway

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
S1P1/Sphingosine-1-phosphate	-0.002	0.1	-9999	-0.37	32	32
PDGFB-D/PDGFRB/SLAP	0.009	0.066	-9999	-0.44	9	9
PDGFB-D/PDGFRB/APS/CBL	0.015	0.069	-9999	-0.47	9	9
AKT1	0.042	0.041	-9999	-10000	0	0
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.006	0.11	-9999	-0.38	32	32
PIK3CA	0.012	0.001	-9999	-10000	0	0
FGR	-0.006	0.06	-9999	-0.43	8	8
mol:Ca2+	0.007	0.048	-9999	-0.32	5	5
MYC	0.013	0.079	-9999	-0.46	7	7
SHC1	0.012	0	-9999	-10000	0	0
HRAS/GDP	0.026	0.045	-9999	-0.38	5	5
LRP1/PDGFRB/PDGFB	0.018	0.059	-9999	-0.47	6	6
GRB10	0.012	0	-9999	-10000	0	0
PTPN11	0.012	0	-9999	-10000	0	0
GO:0007205	0.007	0.048	-9999	-0.32	5	5
PTEN	0.01	0.03	-9999	-0.44	2	2
GRB2	0.012	0	-9999	-10000	0	0
GRB7	-0.001	0.097	-9999	-0.73	8	8
PDGFB-D/PDGFRB/SHP2	0.012	0.059	-9999	-0.55	5	5
PDGFB-D/PDGFRB/GRB10	0.012	0.059	-9999	-0.55	5	5
cell cycle arrest	0.009	0.066	-9999	-0.44	9	9
HRAS	0.011	0.021	-9999	-0.44	1	1
HIF1A	0.045	0.037	-9999	-10000	0	0
GAB1	-0.001	0.066	-9999	-0.38	5	5
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.003	0.069	-9999	-0.4	5	5
PDGFB-D/PDGFRB	0.02	0.053	-9999	-0.48	5	5
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.012	0.059	-9999	-0.55	5	5
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.019	0.099	-9999	-0.44	14	14
positive regulation of MAPKKK cascade	0.012	0.059	-9999	-0.55	5	5
PIK3R1	0.012	0	-9999	-10000	0	0
mol:IP3	0.007	0.048	-9999	-0.33	5	5
E5	0	0.001	-9999	-10000	0	0
CSK	0.012	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.002	0.095	-9999	-0.55	13	13
SHB	0.012	0	-9999	-10000	0	0
BLK	-0.19	0.24	-9999	-0.49	176	176
PTPN2	0.012	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.012	0.059	-9999	-0.55	5	5
BCAR1	0.011	0.021	-9999	-0.44	1	1
VAV2	0	0.071	-9999	-0.38	5	5
CBL	0.012	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.012	0.059	-9999	-0.55	5	5
LCK	-0.008	0.061	-9999	-0.38	10	10
PDGFRB	0.004	0.078	-9999	-0.74	5	5
ACP1	0.012	0	-9999	-10000	0	0
HCK	-0.009	0.089	-9999	-0.45	17	17
ABL1	-0.007	0.066	-9999	-0.39	5	5
PDGFB-D/PDGFRB/CBL	-0.005	0.066	-9999	-0.36	5	5
PTPN1	0.012	0.002	-9999	-10000	0	0
SNX15	0.012	0	-9999	-10000	0	0
STAT3	0.012	0	-9999	-10000	0	0
STAT1	0.011	0.035	-9999	-0.73	1	1
cell proliferation	0.013	0.074	-9999	-0.42	7	7
SLA	0.008	0.042	-9999	-0.44	4	4
actin cytoskeleton reorganization	0.037	0.044	-9999	-10000	0	0
SRC	-0.002	0.043	-9999	-0.39	5	5
PI3K	-0.005	0.038	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.011	0.083	-9999	-0.47	13	13
SH2B2	0.006	0.069	-9999	-0.73	4	4
PLCgamma1/SPHK1	-0.007	0.11	-9999	-0.4	32	32
LYN	-0.001	0.043	-9999	-0.39	5	5
LRP1	0.01	0.03	-9999	-0.44	2	2
SOS1	0.012	0	-9999	-10000	0	0
STAT5B	0.012	0	-9999	-10000	0	0
STAT5A	0.012	0	-9999	-10000	0	0
NCK1-2/p130 Cas	0.032	0.046	-9999	-0.38	5	5
SPHK1	-0.039	0.19	-9999	-0.73	32	32
EDG1	0	0.002	-9999	-10000	0	0
mol:DAG	0.007	0.048	-9999	-0.33	5	5
PLCG1	0.007	0.049	-9999	-0.33	5	5
NHERF/PDGFRB	0.019	0.053	-9999	-0.47	5	5
YES1	-0.003	0.048	-9999	-0.4	6	6
cell migration	0.019	0.053	-9999	-0.47	5	5
SHC/Grb2/SOS1	0.032	0.045	-9999	-0.38	5	5
SLC9A3R2	0.011	0.021	-9999	-0.44	1	1
SLC9A3R1	0.012	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.025	0.051	-9999	-0.42	5	5
FYN	-0.001	0.043	-9999	-0.39	5	5
DOK1	0.022	0.048	-9999	-0.43	5	5
HRAS/GTP	0.008	0.015	-9999	-0.31	1	1
PDGFB	0.011	0.035	-9999	-0.73	1	1
RAC1	0.011	0.073	-9999	-0.38	2	2
PRKCD	0.022	0.048	-9999	-0.43	5	5
FER	0.021	0.049	-9999	-0.43	5	5
MAPKKK cascade	-0.004	0.039	-9999	-0.38	5	5
RASA1	0.022	0.048	-9999	-0.43	5	5
NCK1	0.012	0	-9999	-10000	0	0
NCK2	0.012	0	-9999	-10000	0	0
p62DOK/Csk	0.029	0.044	-9999	-0.39	5	5
PDGFB-D/PDGFRB/SHB	0.012	0.059	-9999	-0.55	5	5
chemotaxis	-0.006	0.065	-9999	-0.38	5	5
STAT1-3-5/STAT1-3-5	-0.004	0.042	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.003	0.059	-9999	-0.56	5	5
PTPRJ	0.012	0	-9999	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.031	0.023	-9999	-0.39	1	1
STMN1	0.022	0.016	-9999	-0.3	1	1
Aurora B/RasGAP/Survivin	0.034	0.024	-9999	-0.45	1	1
Chromosomal passenger complex/Cul3 protein complex	0.007	0.069	-9999	-10000	0	0
BIRC5	0.013	0.034	-9999	-0.72	1	1
DES	-0.34	0.25	-9999	-0.52	292	292
Aurora C/Aurora B/INCENP	0.031	0.018	-9999	-10000	0	0
Aurora B/TACC1	0.022	0.004	-9999	-10000	0	0
Aurora B/PP2A	0.024	0.005	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.015	0.001	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0	0	-9999	-10000	0	0
NDC80	0.023	0.003	-9999	-10000	0	0
Cul3 protein complex	-0.013	0.097	-9999	-0.47	3	3
KIF2C	0.025	0.005	-9999	-10000	0	0
PEBP1	0.013	0	-9999	-10000	0	0
KIF20A	0.012	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.024	0.005	-9999	-10000	0	0
SEPT1	0.006	0.051	-9999	-0.44	6	6
SMC2	0.011	0.021	-9999	-0.44	1	1
SMC4	0.01	0.03	-9999	-0.44	2	2
NSUN2/NPM1/Nucleolin	0.012	0.016	-9999	-10000	0	0
PSMA3	0.012	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.001	-9999	-10000	0	0
H3F3B	0.018	0.003	-9999	-10000	0	0
AURKB	0.02	0.006	-9999	-10000	0	0
AURKC	0.01	0.03	-9999	-0.44	2	2
CDCA8	0.015	0.001	-9999	-10000	0	0
cytokinesis	0.014	0.027	-9999	-10000	0	0
Aurora B/Septin1	0.025	0.035	-9999	-10000	0	0
AURKA	0.012	0.001	-9999	-10000	0	0
INCENP	0.015	0.001	-9999	-10000	0	0
KLHL13	-0.05	0.16	-9999	-0.45	61	61
BUB1	0.012	0	-9999	-10000	0	0
hSgo1/Aurora B/Survivin	0.032	0.031	-9999	-0.42	2	2
EVI5	0.014	0.001	-9999	-10000	0	0
RhoA/GTP	-0.001	0.016	-9999	-10000	0	0
SGOL1	0.011	0.035	-9999	-0.73	1	1
CENPA	0.029	0.009	-9999	-10000	0	0
NCAPG	0.012	0.001	-9999	-10000	0	0
Aurora B/HC8 Proteasome	0.024	0.005	-9999	-10000	0	0
NCAPD2	0.012	0	-9999	-10000	0	0
Aurora B/PP1-gamma	0.024	0.005	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
NCAPH	0.012	0	-9999	-10000	0	0
NPM1	0.007	0.01	-9999	-10000	0	0
RASA1	0.012	0.001	-9999	-10000	0	0
KLHL9	0.012	0	-9999	-10000	0	0
mitotic prometaphase	0.001	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.005	-9999	-10000	0	0
PPP1CC	0.012	0	-9999	-10000	0	0
Centraspindlin	0.046	0.021	-9999	-0.34	1	1
RhoA/GDP	0.009	0	-9999	-10000	0	0
NSUN2	0.007	0.01	-9999	-10000	0	0
MYLK	-0.04	0.12	-9999	-0.28	88	88
KIF23	0.012	0.035	-9999	-0.72	1	1
VIM	0.023	0.003	-9999	-10000	0	0
RACGAP1	0.014	0.001	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	0.007	0.01	-9999	-10000	0	0
Chromosomal passenger complex	0.037	0.009	-9999	-10000	0	0
Chromosomal passenger complex/EVI5	0.06	0.05	-9999	-10000	0	0
TACC1	0.012	0	-9999	-10000	0	0
PPP2R5D	0.012	0	-9999	-10000	0	0
CUL3	0.012	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.015	0.017	-10000	0	-10000	0	0
RAS family/GTP	0.013	0.078	-10000	0	-10000	0	0
NFATC4	0.014	0.069	-10000	0	-0.37	1	1
ERBB2IP	0.006	0.051	-10000	0	-0.43	6	6
HSP90 (dimer)	0.012	0	-10000	0	-10000	0	0
mammary gland morphogenesis	0.002	0.084	-10000	0	-0.5	1	1
JUN	0.032	0.068	-10000	0	-0.27	7	7
HRAS	0.011	0.021	-10000	0	-0.44	1	1
DOCK7	0.008	0.082	-10000	0	-0.47	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.007	0.091	-10000	0	-0.46	4	4
AKT1	0.01	0.002	-10000	0	-10000	0	0
BAD	0.015	0.013	-10000	0	-10000	0	0
MAPK10	-0.004	0.076	-10000	0	-0.24	1	1
mol:GTP	0	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.003	0.09	-10000	0	-0.55	1	1
RAF1	0.022	0.084	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 2	-0.02	0.092	-10000	0	-0.44	4	4
STAT3	0.003	0.006	-10000	0	-10000	0	0
cell migration	0.008	0.071	0.17	2	-10000	0	2
mol:PI-3-4-5-P3	0	0.002	-10000	0	-10000	0	0
cell proliferation	0.005	0.21	-10000	0	-0.6	43	43
FOS	0.023	0.14	-10000	0	-0.41	19	19
NRAS	0.01	0.03	-10000	0	-0.44	2	2
mol:Ca2+	0.002	0.084	-10000	0	-0.5	1	1
MAPK3	0.011	0.17	-10000	0	-0.6	12	12
MAPK1	0.012	0.17	-10000	0	-0.46	42	42
JAK2	0.006	0.083	-10000	0	-0.47	1	1
NF2	-0.001	0.003	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.005	0.085	-10000	0	-0.34	1	1
NRG1	-0.047	0.15	-10000	0	-0.44	60	60
GRB2/SOS1	0.018	0.001	-10000	0	-10000	0	0
MAPK8	0.007	0.091	-10000	0	-0.38	1	1
MAPK9	0.017	0.048	-10000	0	-10000	0	0
ERBB2	-0.001	0.066	0.34	6	-0.56	4	10
ERBB3	0.012	0.002	-10000	0	-10000	0	0
SHC1	0.012	0.001	-10000	0	-10000	0	0
RAC1	0.012	0	-10000	0	-10000	0	0
apoptosis	-0.003	0.014	-10000	0	-10000	0	0
STAT3 (dimer)	0.018	0.005	-10000	0	-10000	0	0
RNF41	0.019	0.016	-10000	0	-10000	0	0
FRAP1	0.008	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.019	0.049	-10000	0	-0.33	1	1
ErbB2/ErbB2/HSP90 (dimer)	0.008	0.053	0.23	6	-0.48	4	10
CHRNA1	-0.003	0.21	-10000	0	-0.63	43	43
myelination	0.014	0.068	-10000	0	-0.36	1	1
PPP3CB	0.007	0.077	-10000	0	-0.44	1	1
KRAS	0.012	0.001	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.007	0.075	-10000	0	-10000	0	0
NRG2	-0.05	0.15	-10000	0	-0.44	59	59
mol:GDP	-0.005	0.085	-10000	0	-0.34	1	1
SOS1	0.012	0.001	-10000	0	-10000	0	0
MAP2K2	0.024	0.091	-10000	0	-10000	0	0
SRC	0.012	0	-10000	0	-10000	0	0
mol:cAMP	0	0.001	-10000	0	-10000	0	0
PTPN11	0.007	0.081	-10000	0	-0.47	1	1
MAP2K1	0.008	0.15	-10000	0	-0.56	12	12
heart morphogenesis	0.002	0.084	-10000	0	-0.5	1	1
RAS family/GDP	0.014	0.076	-10000	0	-10000	0	0
GRB2	0.012	0.001	-10000	0	-10000	0	0
PRKACA	-0.002	0.005	-10000	0	-10000	0	0
CHRNE	0.014	0.031	-10000	0	-0.21	7	7
HSP90AA1	0.012	0	-10000	0	-10000	0	0
activation of caspase activity	-0.01	0.002	-10000	0	-10000	0	0
nervous system development	0.002	0.084	-10000	0	-0.5	1	1
CDC42	0.011	0.021	-10000	0	-0.44	1	1

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.001	0.078	-9999	-0.44	14	14
PDGF/PDGFRA/CRKL	0.01	0.053	-9999	-0.29	14	14
positive regulation of JUN kinase activity	0.024	0.04	-9999	-10000	0	0
CRKL	0.012	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.001	0.065	-9999	-0.56	2	2
AP1	-0.018	0.11	-9999	-0.83	7	7
mol:IP3	0.012	0.056	-9999	-0.3	14	14
PLCG1	0.012	0.056	-9999	-0.3	14	14
PDGF/PDGFRA/alphaV Integrin	0.01	0.053	-9999	-10000	0	0
RAPGEF1	0.011	0.021	-9999	-0.44	1	1
CRK	0.012	0	-9999	-10000	0	0
mol:Ca2+	0.012	0.056	-9999	-0.3	14	14
CAV3	-0.001	0.049	-9999	-0.73	2	2
CAV1	0.008	0.042	-9999	-0.44	4	4
SHC/Grb2/SOS1	0.025	0.04	-9999	-10000	0	0
PDGF/PDGFRA/Shf	-0.008	0.11	-9999	-0.42	28	28
FOS	0.017	0.11	-9999	-0.82	7	7
JUN	-0.002	0.008	-9999	-10000	0	0
oligodendrocyte development	0.009	0.053	-9999	-10000	0	0
GRB2	0.012	0	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
mol:DAG	0.012	0.056	-9999	-0.3	14	14
PDGF/PDGFRA	-0.001	0.077	-9999	-0.44	14	14
actin cytoskeleton reorganization	0.009	0.053	-9999	-10000	0	0
SRF	0.018	0.004	-9999	-10000	0	0
SHC1	0.012	0	-9999	-10000	0	0
PI3K	0.018	0.045	-9999	-10000	0	0
PDGF/PDGFRA/Crk/C3G	0.017	0.046	-9999	-10000	0	0
JAK1	0.01	0.056	-9999	-10000	0	0
ELK1/SRF	0.025	0.042	-9999	-10000	0	0
SHB	0.012	0	-9999	-10000	0	0
SHF	-0.01	0.12	-9999	-0.71	14	14
CSNK2A1	0.009	0.007	-9999	-10000	0	0
GO:0007205	0.011	0.061	-9999	-0.33	14	14
SOS1	0.012	0	-9999	-10000	0	0
Ras protein signal transduction	0.024	0.04	-9999	-10000	0	0
PDGF/PDGFRA/SHB	0.01	0.053	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-1	0.007	0.066	-9999	-0.33	16	16
ITGAV	0.012	0	-9999	-10000	0	0
ELK1	0.017	0.053	-9999	-10000	0	0
PIK3CA	0.012	0.001	-9999	-10000	0	0
PDGF/PDGFRA/Crk	0.01	0.053	-9999	-10000	0	0
JAK-STAT cascade	0.01	0.055	-9999	-10000	0	0
cell proliferation	-0.008	0.11	-9999	-0.42	28	28

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.019	0.015	-10000	0	-0.3	1	1
MAP4K4	0.036	0.029	-10000	0	-10000	0	0
BAG4	0.012	0.001	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.013	0.031	-10000	0	-10000	0	0
NFKBIA	0.012	0	-10000	0	-10000	0	0
BIRC3	0.004	0.065	-10000	0	-0.47	8	8
BAX	-0.004	0.015	-10000	0	-10000	0	0
RIPK1	0.012	0	-10000	0	-10000	0	0
AKT1	0.017	0.006	-10000	0	-10000	0	0
BAD	-0.015	0.03	-10000	0	-10000	0	0
SMPD1	0.021	0.031	-10000	0	-0.24	5	5
RB1	-0.014	0.031	-10000	0	-10000	0	0
FADD/Caspase 8	0.044	0.028	-10000	0	-10000	0	0
MAP2K4	-0.01	0.034	-10000	0	-0.21	4	4
NSMAF	0.012	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.008	0.029	-10000	0	-10000	0	0
EGF	-0.089	0.21	-10000	0	-0.49	91	91
mol:ceramide	-0.022	0.032	-10000	0	-10000	0	0
MADD	0.012	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.019	0	-10000	0	-10000	0	0
ASAH1	0.012	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.015	0.03	-10000	0	-10000	0	0
cell proliferation	-0.034	0.085	-10000	0	-10000	0	0
BID	0.024	0.03	-10000	0	-0.31	1	1
MAP3K1	-0.015	0.032	-10000	0	-0.22	1	1
EIF2A	-0.002	0.029	-10000	0	-10000	0	0
TRADD	0.012	0	-10000	0	-10000	0	0
CRADD	0.012	0	-10000	0	-10000	0	0
MAPK3	0.001	0.027	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.001	0.027	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.013	0.031	-10000	0	-10000	0	0
FADD	0.036	0.029	-10000	0	-10000	0	0
KSR1	-0.014	0.031	-10000	0	-10000	0	0
MAPK8	-0.004	0.031	-10000	0	-10000	0	0
PRKRA	-0.014	0.031	-10000	0	-10000	0	0
PDGFA	0.012	0	-10000	0	-10000	0	0
TRAF2	0.011	0.021	-10000	0	-0.44	1	1
IGF1	-0.1	0.19	-10000	0	-0.44	114	114
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.022	0.032	-10000	0	-10000	0	0
CTSD	0.011	0.021	-10000	0	-0.44	1	1
regulation of nitric oxide biosynthetic process	0.018	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.035	0.09	-10000	0	-10000	0	0
PRKCD	0.012	0	-10000	0	-10000	0	0
PRKCZ	0.012	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.019	0	-10000	0	-10000	0	0
RelA/NF kappa B1	0.018	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.012	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.032	0.031	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.024	0.018	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.019	0.015	-10000	0	-0.3	1	1
MAP2K1	-0.002	0.028	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.012	0	-10000	0	-10000	0	0
CYCS	-0.001	0.036	0.14	17	-10000	0	17
TNFRSF1A	0.012	0	-10000	0	-10000	0	0
NFKB1	0.012	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.018	0.001	-10000	0	-10000	0	0
EIF2AK2	-0.008	0.03	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	0.024	0.018	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.036	0.019	-10000	0	-10000	0	0
MAP2K2	-0.002	0.027	-10000	0	-10000	0	0
SMPD3	0.019	0.053	-10000	0	-0.3	11	11
TNF	0.01	0.03	-10000	0	-0.44	2	2
PKC zeta/PAR4	0.018	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.033	0.084	0.2	91	-10000	0	91
NF kappa B1/RelA/I kappa B alpha	0.037	0	-10000	0	-10000	0	0
AIFM1	-0.001	0.037	0.14	18	-10000	0	18
BCL2	-0.009	0.096	-10000	0	-0.44	22	22

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.017	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.012	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.008	0.042	-9999	-0.44	4	4
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.009	0.036	-9999	-0.44	3	3
RAC1-CDC42/GTP/PAK family	0.021	0.01	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0.011	0.021	-9999	-0.44	1	1
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.012	0	-9999	-10000	0	0
FYN	0.012	0	-9999	-10000	0	0
MAP3K12	0.012	0	-9999	-10000	0	0
FGR	0.008	0.05	-9999	-0.51	4	4
p38 alpha/TAB1	-0.035	0.05	-9999	-0.31	2	2
PRKG1	-0.009	0.096	-9999	-0.44	22	22
DUSP8	0.011	0.021	-9999	-0.44	1	1
PGK/cGMP/p38 alpha	-0.04	0.065	-9999	-0.3	15	15
apoptosis	-0.034	0.049	-9999	-0.3	2	2
RAL/GTP	0.017	0	-9999	-10000	0	0
LYN	0.012	0	-9999	-10000	0	0
DUSP1	0.01	0.03	-9999	-0.44	2	2
PAK1	0.012	0	-9999	-10000	0	0
SRC	0.012	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.031	0.012	-9999	-10000	0	0
TRAF6	0.012	0	-9999	-10000	0	0
RAC1	0.012	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	0.011	0.021	-9999	-0.44	1	1
RAC1-CDC42/GTP	0.016	0.013	-9999	-0.25	1	1
MAPK11	-0.021	0.098	-9999	-0.34	9	9
BLK	-0.16	0.22	-9999	-0.44	173	173
HCK	0.001	0.072	-9999	-0.44	12	12
MAP2K3	0.012	0	-9999	-10000	0	0
DUSP16	0.012	0	-9999	-10000	0	0
DUSP10	0.006	0.069	-9999	-0.73	4	4
TRAF6/MEKK3	0.016	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	-0.007	0.077	-9999	-0.28	5	5
positive regulation of innate immune response	-0.017	0.1	-9999	-0.36	9	9
LCK	-0.001	0.096	-9999	-0.66	9	9
p38alpha-beta/MKP7	-0.01	0.1	-9999	-0.46	2	2
p38alpha-beta/MKP5	-0.013	0.11	-9999	-0.46	4	4
PGK/cGMP	-0.006	0.068	-9999	-0.31	22	22
PAK2	0.012	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.011	0.1	-9999	-0.39	4	4
CDC42	0.011	0.021	-9999	-0.44	1	1
RALB	0.012	0	-9999	-10000	0	0
RALA	0.012	0	-9999	-10000	0	0
PAK3	0.007	0.006	-9999	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.001	0.076	-10000	0	-0.42	5	5
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.002	0.037	-10000	0	-0.56	2	2
GNB1/GNG2	0.006	0.054	-10000	0	-10000	0	0
GNB1	0.012	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	-0.006	0.057	-10000	0	-0.23	27	27
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	0.004	0.015	0.064	27	-10000	0	27
GNAL	-0.014	0.11	-10000	0	-0.44	27	27
GNG2	-0.006	0.089	-10000	0	-0.44	19	19
CRH	-0.003	0.048	-10000	0	-0.73	2	2
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0	-10000	0	-10000	0	0
MAPK11	0.006	0.022	-10000	0	-0.32	2	2

×

FOXM1 transcription factor network

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
NFATC3	0.15	0.25	-9999	-1.1	1	1
PLK1	0.059	0.052	-9999	-0.54	1	1
BIRC5	0.059	0.053	-9999	-0.56	1	1
HSPA1B	0.13	0.27	-9999	-1	2	2
MAP2K1	0.039	0.029	-9999	-10000	0	0
BRCA2	0.15	0.26	-9999	-1.1	1	1
FOXM1	0.15	0.27	-9999	-1.3	1	1
XRCC1	0.15	0.25	-9999	-1.1	1	1
FOXM1B/p19	-0.11	0.19	-9999	-0.89	6	6
Cyclin D1/CDK4	0.14	0.24	-9999	-0.91	2	2
CDC2	0.15	0.26	-9999	-1.1	1	1
TGFA	0.15	0.24	-9999	-0.92	1	1
SKP2	0.15	0.25	-9999	-1.1	1	1
CCNE1	0.013	0.061	-9999	-0.73	3	3
CKS1B	0.15	0.25	-9999	-1.1	1	1
RB1	-0.023	0.065	-9999	-10000	0	0
FOXM1C/SP1	0.14	0.25	-9999	-1.2	1	1
AURKB	0.06	0.044	-9999	-10000	0	0
CENPF	0.15	0.25	-9999	-1.1	1	1
CDK4	0.021	0.037	-9999	-0.73	1	1
MYC	0.14	0.24	-9999	-0.92	1	1
CHEK2	0.039	0.029	-9999	-10000	0	0
ONECUT1	0.14	0.25	-9999	-1	1	1
CDKN2A	-0.16	0.31	-9999	-0.74	101	101
LAMA4	0.15	0.25	-9999	-1.1	1	1
FOXM1B/HNF6	0.14	0.26	-9999	-1.2	1	1
FOS	0.14	0.28	-9999	-1	8	8
SP1	0.013	0.004	-9999	-10000	0	0
CDC25B	0.14	0.27	-9999	-1.1	2	2
response to radiation	0.023	0.026	-9999	-10000	0	0
CENPB	0.15	0.25	-9999	-1.1	1	1
CENPA	0.15	0.25	-9999	-1.1	1	1
NEK2	0.15	0.25	-9999	-1.1	1	1
HIST1H2BA	0.14	0.25	-9999	-1.1	1	1
CCNA2	0.018	0.007	-9999	-10000	0	0
EP300	0.012	0	-9999	-10000	0	0
CCNB1/CDK1	0.15	0.26	-9999	-1.2	1	1
CCNB2	0.15	0.25	-9999	-1.1	1	1
CCNB1	0.15	0.26	-9999	-1.1	1	1
ETV5	0.15	0.26	-9999	-1.1	1	1
ESR1	0.083	0.41	-9999	-1.1	42	42
CCND1	0.15	0.25	-9999	-0.93	2	2
GSK3A	0.035	0.025	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.046	0.052	-9999	-0.47	3	3
CDK2	0.018	0.007	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.026	0.031	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.046	0.14	-9999	-1.1	1	1
GAS1	0.05	0.46	-9999	-1	60	60
MMP2	0.14	0.26	-9999	-1.2	3	3
RB1/FOXM1C	0.15	0.24	-9999	-1	1	1
CREBBP	0.012	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.021	0.05	-9999	-10000	0	0
HDAC3	0.012	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0.015	0.004	-9999	-10000	0	0
GATA1/HDAC5	0.014	0.016	-9999	-10000	0	0
GATA2/HDAC5	0.01	0.051	-9999	-0.3	12	12
HDAC5/BCL6/BCoR	0.025	0.013	-9999	-10000	0	0
HDAC9	-0.053	0.16	-9999	-0.44	67	67
Glucocorticoid receptor/Hsp90/HDAC6	0.006	0.069	-9999	-10000	0	0
HDAC4/ANKRA2	0.018	0	-9999	-10000	0	0
HDAC5/YWHAB	0.018	0.015	-9999	-0.3	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.018	0.013	-9999	-10000	0	0
GATA2	0.002	0.069	-9999	-0.44	11	11
HDAC4/RFXANK	0.018	0	-9999	-10000	0	0
BCOR	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.011	0.021	-9999	-0.44	1	1
HDAC5	0.011	0.021	-9999	-0.44	1	1
GNB1/GNG2	0.005	0.064	-9999	-0.3	19	19
Histones	0.004	0.074	-9999	-0.39	1	1
ADRBK1	0.012	0	-9999	-10000	0	0
HDAC4	0.012	0	-9999	-10000	0	0
XPO1	0.012	0	-9999	-10000	0	0
HDAC5/ANKRA2	0.018	0.015	-9999	-0.3	1	1
HDAC4/Ubc9	0.018	0	-9999	-10000	0	0
HDAC7	0.012	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0.018	0.015	-9999	-10000	0	0
TUBA1B	0.012	0	-9999	-10000	0	0
HDAC6	0.012	0	-9999	-10000	0	0
HDAC5/RFXANK	0.018	0.015	-9999	-0.3	1	1
CAMK4	-0.016	0.11	-9999	-0.44	29	29
Tubulin/HDAC6	0.016	0.065	-9999	-0.47	8	8
SUMO1	0.01	0.03	-9999	-0.44	2	2
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.012	0	-9999	-10000	0	0
GATA1	0.008	0.006	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.012	0	-9999	-10000	0	0
NR3C1	-0.019	0.11	-9999	-0.44	32	32
SUMO1/HDAC4	0.026	0.021	-9999	-0.28	2	2
SRF	0.012	0	-9999	-10000	0	0
HDAC4/YWHAB	0.018	0	-9999	-10000	0	0
Tubulin	0.008	0.075	-9999	-0.55	8	8
HDAC4/14-3-3 E	0.018	0	-9999	-10000	0	0
GNB1	0.012	0	-9999	-10000	0	0
RANGAP1	0.012	0	-9999	-10000	0	0
BCL6/BCoR	0.018	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.025	0.013	-9999	-10000	0	0
HDAC4/SRF	0.008	0.066	-9999	-10000	0	0
HDAC4/ER alpha	-0.011	0.092	-9999	-0.3	42	42
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.004	0.074	-9999	-0.38	1	1
cell motility	0.016	0.065	-9999	-0.47	8	8
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.012	0	-9999	-10000	0	0
HDAC7/HDAC3	0.018	0	-9999	-10000	0	0
BCL6	0.012	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.012	0	-9999	-10000	0	0
Hsp90/HDAC6	0.018	0	-9999	-10000	0	0
ESR1	-0.029	0.13	-9999	-0.44	42	42
HDAC6/HDAC11	0.018	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.029	0.012	-9999	-10000	0	0
NPC	0.007	0	-9999	-10000	0	0
MEF2C	0	0.075	-9999	-0.44	13	13
RAN	0.012	0	-9999	-10000	0	0
HDAC4/MEF2C	0.03	0.04	-9999	-10000	0	0
GNG2	-0.006	0.089	-9999	-0.44	19	19
NCOR2	0.011	0.021	-9999	-0.44	1	1
TUBB2A	-0.001	0.097	-9999	-0.73	8	8
HDAC11	0.012	0	-9999	-10000	0	0
HSP90AA1	0.012	0	-9999	-10000	0	0
RANBP2	0.012	0	-9999	-10000	0	0
ANKRA2	0.012	0	-9999	-10000	0	0
RFXANK	0.012	0	-9999	-10000	0	0
nuclear import	-0.025	0.013	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.012	0	-9999	-10000	0	0
HDAC2	0.012	0	-9999	-10000	0	0
GNB1/GNG2	0.014	0.054	-9999	-10000	0	0
forebrain development	0.019	0.079	-9999	-0.5	5	5
GNAO1	-0.11	0.2	-9999	-0.44	125	125
SMO/beta Arrestin2	0.021	0.004	-9999	-10000	0	0
SMO	0.014	0.002	-9999	-10000	0	0
ARRB2	0.013	0.002	-9999	-10000	0	0
GLI3/SPOP	0.024	0.065	-9999	-10000	0	0
mol:GTP	0.001	0.001	-9999	-10000	0	0
GSK3B	0.012	0	-9999	-10000	0	0
GNAI2	0.013	0.001	-9999	-10000	0	0
SIN3/HDAC complex	0.031	0.002	-9999	-10000	0	0
GNAI1	-0.001	0.077	-9999	-0.44	14	14
XPO1	0.015	0.003	-9999	-10000	0	0
GLI1/Su(fu)	0.028	0.065	-9999	-0.47	3	3
SAP30	0.012	0	-9999	-10000	0	0
mol:GDP	0.013	0.002	-9999	-10000	0	0
MIM/GLI2A	0.012	0.053	-9999	-0.43	6	6
IFT88	0.012	0.001	-9999	-10000	0	0
GNAI3	0.013	0.001	-9999	-10000	0	0
GLI2	0.037	0.017	-9999	-10000	0	0
GLI3	0.017	0.068	-9999	-10000	0	0
CSNK1D	0.012	0	-9999	-10000	0	0
CSNK1E	0.012	0	-9999	-10000	0	0
SAP18	0.012	0	-9999	-10000	0	0
embryonic digit morphogenesis	0.012	0.001	-9999	-10000	0	0
GNG2	-0.006	0.089	-9999	-0.44	19	19
Gi family/GTP	-0.037	0.12	-9999	-0.38	15	15
SIN3B	0.012	0	-9999	-10000	0	0
SIN3A	0.012	0	-9999	-10000	0	0
GLI3/Su(fu)	0.04	0.05	-9999	-10000	0	0
GLI2/Su(fu)	0.051	0.018	-9999	-10000	0	0
FOXA2	-0.022	0.14	-9999	-0.67	18	18
neural tube patterning	0.019	0.079	-9999	-0.5	5	5
SPOP	0.012	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.03	0.003	-9999	-10000	0	0
GNB1	0.012	0	-9999	-10000	0	0
CSNK1G2	0.011	0.021	-9999	-0.44	1	1
CSNK1G3	0.012	0	-9999	-10000	0	0
MTSS1	0.012	0.053	-9999	-0.44	6	6
embryonic limb morphogenesis	0.019	0.079	-9999	-0.5	5	5
SUFU	0.026	0.005	-9999	-10000	0	0
LGALS3	0.011	0.021	-9999	-0.44	1	1
catabolic process	0.046	0.062	-9999	-10000	0	0
GLI3A/CBP	0.018	0.027	-9999	-0.31	1	1
KIF3A	0.012	0.001	-9999	-10000	0	0
GLI1	0.019	0.081	-9999	-0.51	5	5
RAB23	0.012	0.001	-9999	-10000	0	0
CSNK1A1	0.012	0	-9999	-10000	0	0
IFT172	0.012	0	-9999	-10000	0	0
RBBP7	0.012	0	-9999	-10000	0	0
Su(fu)/Galectin3	0.03	0.012	-9999	-10000	0	0
GNAZ	0.008	0.047	-9999	-0.44	5	5
RBBP4	0.012	0	-9999	-10000	0	0
CSNK1G1	0.011	0.021	-9999	-0.44	1	1
PIAS1	0.012	0	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
GLI2/SPOP	0.041	0.016	-9999	-10000	0	0
STK36	0.015	0.003	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.034	0.13	-9999	-0.43	23	23
PTCH1	0.022	0.1	-9999	-0.94	3	3
MIM/GLI1	0.024	0.11	-9999	-0.51	10	10
CREBBP	0.018	0.027	-9999	-0.31	1	1
Su(fu)/SIN3/HDAC complex	0.042	0.002	-9999	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.001	0.077	-10000	0	-0.44	14	14
HRAS	0.011	0.021	-10000	0	-0.44	1	1
EGFR	0.011	0.021	-10000	0	-0.44	1	1
AKT	0.029	0.04	-10000	0	-0.28	6	6
FOXO3	0.012	0	-10000	0	-10000	0	0
AKT1	0.012	0	-10000	0	-10000	0	0
FOXO1	0.011	0.021	-10000	0	-0.44	1	1
AKT3	0.005	0.055	-10000	0	-0.44	7	7
FOXO4	0.012	0	-10000	0	-10000	0	0
MET	0.004	0.077	-10000	0	-0.73	5	5
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
PIK3CB	0.012	0.001	-10000	0	-10000	0	0
NRAS	0.01	0.03	-10000	0	-0.44	2	2
PIK3CG	-0.057	0.16	-10000	0	-0.44	71	71
PIK3R3	0.012	0	-10000	0	-10000	0	0
PIK3R2	0.012	0	-10000	0	-10000	0	0
NF1	0.012	0	-10000	0	-10000	0	0
RAS	0.015	0.037	-10000	0	-0.26	2	2
ERBB2	0.006	0.069	-10000	0	-0.73	4	4
proliferation/survival/translation	-0.018	0.04	0.2	6	-10000	0	6
PI3K	0.01	0.053	-10000	0	-0.26	3	3
PIK3R1	0.012	0	-10000	0	-10000	0	0
KRAS	0.012	0	-10000	0	-10000	0	0
FOXO	0.039	0.019	-10000	0	-10000	0	0
AKT2	0.012	0	-10000	0	-10000	0	0
PTEN	0.01	0.03	-10000	0	-0.44	2	2

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.008	0.042	0.44	4	-10000	0	4
PI3K Class IB/PDE3B	0.008	0.042	-10000	0	-0.44	4	4
PDE3B	0.008	0.042	-10000	0	-0.44	4	4

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.046	0.084	-9999	-0.53	1	1
CRKL	0.03	0.049	-9999	-0.44	1	1
mol:DAG	0.034	0.05	-9999	-0.42	1	1
HRAS	0.047	0.044	-9999	-10000	0	0
MAPK8	0.024	0.046	-9999	-0.4	5	5
RAP1A	0.03	0.049	-9999	-0.44	1	1
GAB1	0.03	0.049	-9999	-0.44	1	1
MAPK14	0.024	0.046	-9999	-0.4	5	5
EPO	0.003	0.069	-9999	-0.73	4	4
PLCG1	0.034	0.051	-9999	-0.43	1	1
EPOR/TRPC2/IP3 Receptors	0.012	0.035	-9999	-0.72	1	1
RAPGEF1	0.011	0.021	-9999	-0.44	1	1
EPO/EPOR (dimer)/SOCS3	0.019	0.056	-9999	-0.46	6	6
GAB1/SHC/GRB2/SOS1	-0.006	0.035	-9999	-10000	0	0
EPO/EPOR (dimer)	0.012	0.06	-9999	-0.55	5	5
IRS2	0.03	0.049	-9999	-0.44	1	1
STAT1	0.038	0.069	-9999	-0.53	1	1
STAT5B	0.036	0.06	-9999	-0.48	1	1
cell proliferation	0.028	0.043	-9999	-0.37	5	5
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.006	0.034	-9999	-10000	0	0
TEC	0.029	0.053	-9999	-0.41	2	2
SOCS3	0.011	0.035	-9999	-0.73	1	1
STAT1 (dimer)	0.038	0.068	-9999	-0.52	1	1
JAK2	0.01	0.037	-9999	-0.44	3	3
PIK3R1	0.012	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.038	0.054	-9999	-0.37	5	5
EPO/EPOR	0.012	0.06	-9999	-0.55	5	5
LYN	0.013	0.003	-9999	-10000	0	0
TEC/VAV2	0.032	0.06	-9999	-0.43	1	1
elevation of cytosolic calcium ion concentration	0.012	0.035	-9999	-0.72	1	1
SHC1	0.012	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.025	0.052	-9999	-0.46	5	5
mol:IP3	0.034	0.05	-9999	-0.42	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.04	0.047	-9999	-0.4	1	1
SH2B3	0.013	0.005	-9999	-10000	0	0
NFKB1	0.024	0.046	-9999	-0.4	5	5
EPO/EPOR (dimer)/JAK2/SOCS3	-0.004	0.032	-9999	-0.26	1	1
PTPN6	0.024	0.051	-9999	-0.37	5	5
TEC/VAV2/GRB2	0.037	0.058	-9999	-0.41	1	1
EPOR	0.012	0.035	-9999	-0.72	1	1
INPP5D	0.011	0.021	-9999	-0.44	1	1
mol:GDP	-0.006	0.036	-9999	-10000	0	0
SOS1	0.012	0	-9999	-10000	0	0
PLCG2	-0.032	0.13	-9999	-0.44	45	45
CRKL/CBL/C3G	0.042	0.048	-9999	-0.41	1	1
VAV2	0.026	0.058	-9999	-0.44	1	1
CBL	0.03	0.049	-9999	-0.44	1	1
SHC/Grb2/SOS1	-0.007	0.037	-9999	-0.41	1	1
STAT5A	0.036	0.06	-9999	-0.48	1	1
GRB2	0.012	0	-9999	-10000	0	0
STAT5 (dimer)	0.047	0.082	-9999	-0.61	1	1
LYN/PLCgamma2	-0.013	0.095	-9999	-0.3	45	45
PTPN11	0.012	0	-9999	-10000	0	0
BTK	0.001	0.092	-9999	-0.43	3	3
BCL2	0.022	0.19	-9999	-0.81	22	22

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.024	0.026	-9999	-10000	0	0
epithelial cell differentiation	0.027	0	-9999	-10000	0	0
CYFIP2	0.011	0.021	-9999	-0.44	1	1
ENAH	0.051	0.017	-9999	-10000	0	0
EGFR	0.011	0.021	-9999	-0.44	1	1
EPHA2	0.011	0.035	-9999	-0.73	1	1
MYO6	0.031	0	-9999	-10000	0	0
CTNNB1	0.012	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	0.025	0.013	-9999	-10000	0	0
AQP5	-0.023	0.11	-9999	-10000	0	0
CTNND1	0.012	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.031	0.01	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.021	0.046	-9999	-10000	0	0
EGF	-0.089	0.21	-9999	-0.49	91	91
NCKAP1	0.012	0	-9999	-10000	0	0
AQP3	0.029	0.061	-9999	-0.39	1	1
cortical microtubule organization	0.027	0	-9999	-10000	0	0
GO:0000145	0.028	0.01	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.029	0	-9999	-10000	0	0
MLLT4	0.011	0.021	-9999	-0.44	1	1
ARF6/GDP	-0.001	0.016	-9999	-10000	0	0
ARF6	0.012	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.03	0.024	-9999	-0.43	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.039	0.007	-9999	-10000	0	0
PVRL2	0.012	0	-9999	-10000	0	0
ZYX	0.031	0	-9999	-10000	0	0
ARF6/GTP	0.033	0.023	-9999	-0.4	1	1
CDH1	0.012	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.043	0.091	-9999	-0.37	17	17
RhoA/GDP	0	0	-9999	-10000	0	0
actin cytoskeleton organization	0.035	0	-9999	-10000	0	0
IGF-1R heterotetramer	0.012	0	-9999	-10000	0	0
GIT1	0.011	0.021	-9999	-0.44	1	1
IGF1R	0.012	0	-9999	-10000	0	0
IGF1	-0.1	0.19	-9999	-0.44	114	114
DIAPH1	-0.001	0.025	-9999	-0.54	1	1
Wnt receptor signaling pathway	-0.027	0	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
RhoA/GTP	-0.001	0.016	-9999	-10000	0	0
CTNNA1	0.012	0	-9999	-10000	0	0
VCL	0.036	0	-9999	-10000	0	0
EFNA1	0.012	0	-9999	-10000	0	0
LPP	0.035	0.01	-9999	-10000	0	0
Ephrin A1/EPHA2	-0.001	0.017	-9999	-0.37	1	1
SEC6/SEC8	0	0.007	-9999	-10000	0	0
MGAT3	0.021	0.047	-9999	-10000	0	0
HGF/MET	-0.008	0.048	-9999	-0.37	6	6
HGF	0.003	0.068	-9999	-0.47	9	9
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.024	0.026	-9999	-10000	0	0
actin cable formation	0.065	0.015	-9999	-10000	0	0
KIAA1543	0.035	0.01	-9999	-10000	0	0
KIFC3	0.016	0.079	-9999	-0.39	17	17
NCK1	0.012	0	-9999	-10000	0	0
EXOC3	0.012	0	-9999	-10000	0	0
ACTN1	0.031	0	-9999	-10000	0	0
NCK1/GIT1	0.018	0.015	-9999	-0.3	1	1
mol:GDP	0.027	0	-9999	-10000	0	0
EXOC4	0.012	0	-9999	-10000	0	0
STX4	0.031	0	-9999	-10000	0	0
PIP5K1C	0.031	0.01	-9999	-10000	0	0
LIMA1	0.006	0.051	-9999	-0.44	6	6
ABI1	0.012	0	-9999	-10000	0	0
ROCK1	0.049	0.02	-9999	-10000	0	0
adherens junction assembly	0.038	0.059	-9999	-0.54	1	1
IGF-1R heterotetramer/IGF1	-0.044	0.076	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.018	0.015	-9999	-0.3	1	1
MET	0.004	0.077	-9999	-0.73	5	5
PLEKHA7	0.031	0	-9999	-10000	0	0
mol:GTP	0.029	0.024	-9999	-0.43	1	1
establishment of epithelial cell apical/basal polarity	0.049	0.009	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0.024	0.026	-9999	-10000	0	0
regulation of cell-cell adhesion	0.035	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.024	0.026	-9999	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.039	0.14	-10000	0	-0.44	52	52
CLTC	0.022	0.039	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.022	0.007	-10000	0	-10000	0	0
Dynamin 2/GTP	0.011	0.067	-10000	0	-0.44	10	10
EXOC4	0.012	0	-10000	0	-10000	0	0
CD59	0.021	0.024	-10000	0	-10000	0	0
CPE	-0.003	0.071	-10000	0	-0.26	32	32
CTNNB1	0.012	0	-10000	0	-10000	0	0
membrane fusion	0.022	0.007	-10000	0	-10000	0	0
CTNND1	0.017	0.063	-10000	0	-0.4	10	10
DNM2	0.012	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.024	0.019	-10000	0	-10000	0	0
TSHR	0.01	0.033	-10000	0	-0.25	7	7
INS	0.009	0.007	-10000	0	-10000	0	0
BIN1	0.011	0.021	-10000	0	-0.44	1	1
mol:Choline	0.022	0.007	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.005	0.072	-10000	0	-0.48	10	10
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.012	0	-10000	0	-10000	0	0
mol:Ca2+	0.011	0.066	-10000	0	-0.43	10	10
JUP	0.02	0.025	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0.023	0.011	-10000	0	-10000	0	0
ARF6/GTP	0.009	0	-10000	0	-10000	0	0
CDH1	0.021	0.024	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0.009	0	-10000	0	-10000	0	0
MAPK8IP3	0.01	0.041	-10000	0	-0.58	2	2
positive regulation of endocytosis	0.009	0	-10000	0	-10000	0	0
EXOC2	0.011	0.021	-10000	0	-0.44	1	1
substrate adhesion-dependent cell spreading	0.035	0.035	-10000	0	-0.65	1	1
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.012	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.007	0.048	0.33	10	-10000	0	10
positive regulation of phagocytosis	0.016	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.015	0.026	-10000	0	-0.37	2	2
ACAP1	0.016	0.027	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.023	0.082	-10000	0	-0.41	2	2
clathrin heavy chain/ACAP1	0.025	0.035	-10000	0	-10000	0	0
JIP4/KLC1	0.024	0	-10000	0	-10000	0	0
EXOC1	0.011	0.021	-10000	0	-0.44	1	1
exocyst	0.035	0.035	-10000	0	-0.66	1	1
RALA/GTP	0.009	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.017	0	-10000	0	-10000	0	0
receptor recycling	0.009	0	-10000	0	-10000	0	0
CTNNA1	0.017	0.063	-10000	0	-0.4	10	10
NME1	0.005	0.073	-10000	0	-0.48	10	10
clathrin coat assembly	0.021	0.038	-10000	0	-10000	0	0
IL2RA	0.016	0.037	-10000	0	-10000	0	0
VAMP3	0.016	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.023	0.061	-10000	0	-0.38	2	2
EXOC6	0.012	0	-10000	0	-10000	0	0
PLD1	0.019	0.012	-10000	0	-0.24	1	1
PLD2	0.019	0	-10000	0	-10000	0	0
EXOC5	0.009	0.036	-10000	0	-0.44	3	3
PIP5K1C	0.024	0.02	-10000	0	-10000	0	0
SDC1	0.021	0.024	-10000	0	-10000	0	0
ARF6/GDP	0.006	0.072	-10000	0	-0.48	10	10
EXOC7	0.012	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.007	0.05	-10000	0	-0.34	10	10
mol:Phosphatidic acid	0.022	0.007	-10000	0	-10000	0	0
endocytosis	-0.022	0.011	-10000	0	-10000	0	0
SCAMP2	0.012	0	-10000	0	-10000	0	0
ADRB2	-0.009	0.09	-10000	0	-0.39	5	5
EXOC3	0.012	0	-10000	0	-10000	0	0
ASAP2	0.012	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.013	0.066	-10000	0	-0.43	10	10
KLC1	0.012	0	-10000	0	-10000	0	0
AVPR2	0.006	0.079	-10000	0	-0.38	7	7
RALA	0.012	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.007	0.045	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.029	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0.02	0	-9999	-10000	0	0
mol:DAG	0.019	0.078	-9999	-0.42	14	14
VEGFR1 homodimer/NRP1/VEGFR 121	0.025	0.021	-9999	-0.43	1	1
CaM/Ca2+	0.025	0.074	-9999	-0.39	14	14
HIF1A	0.02	0	-9999	-10000	0	0
GAB1	0.012	0	-9999	-10000	0	0
AKT1	0.037	0.064	-9999	-10000	0	0
PLCG1	0.019	0.079	-9999	-0.42	14	14
NOS3	0.037	0.07	-9999	-10000	0	0
CBL	0.012	0	-9999	-10000	0	0
mol:NO	0.037	0.068	-9999	-10000	0	0
FLT1	0.027	0	-9999	-10000	0	0
PGF	-0.01	0.13	-9999	-0.73	14	14
VEGFR1 homodimer/NRP2/VEGFR121	0.032	0.029	-9999	-0.42	1	1
CALM1	0.012	0	-9999	-10000	0	0
PIK3CA	0.012	0.001	-9999	-10000	0	0
eNOS/Hsp90	0.043	0.067	-9999	-10000	0	0
endothelial cell proliferation	-0.011	0.1	-9999	-0.5	1	1
mol:Ca2+	0.019	0.078	-9999	-0.42	14	14
MAPK3	0.028	0.07	-9999	-10000	0	0
MAPK1	0.029	0.069	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
PLGF homodimer	-0.01	0.13	-9999	-0.73	14	14
PRKACA	0.012	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	0.008	0.042	-9999	-0.44	4	4
VEGFA homodimer	0.011	0.035	-9999	-0.73	1	1
VEGFR1 homodimer/VEGFA homodimer	0.028	0.023	-9999	-0.47	1	1
platelet activating factor biosynthetic process	0.033	0.068	-9999	-10000	0	0
PI3K	0.028	0.075	-9999	-10000	0	0
PRKCA	0.024	0.073	-9999	-10000	0	0
PRKCB	-0.028	0.12	-9999	-0.4	14	14
VEGFR1 homodimer/PLGF homodimer	0.014	0.086	-9999	-0.47	14	14
VEGFA	0.011	0.035	-9999	-0.73	1	1
VEGFB	0.012	0	-9999	-10000	0	0
mol:IP3	0.019	0.078	-9999	-0.42	14	14
RASA1	0.033	0	-9999	-10000	0	0
NRP2	0.009	0.036	-9999	-0.44	3	3
VEGFR1 homodimer	0.027	0	-9999	-10000	0	0
VEGFB homodimer	0.012	0	-9999	-10000	0	0
NCK1	0.012	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.041	0.069	-9999	-10000	0	0
PTPN11	0.012	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.026	0.074	-9999	-0.39	14	14
mol:L-citrulline	0.037	0.068	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.033	0.043	-9999	-0.4	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.034	0.021	-9999	-0.42	1	1
CD2AP	0	0.075	-9999	-0.44	13	13
PI3K/GAB1	0.032	0.071	-9999	-10000	0	0
PDPK1	0.029	0.07	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.034	0.021	-9999	-0.42	1	1
mol:NADP	0.037	0.068	-9999	-10000	0	0
HSP90AA1	0.012	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.032	0.043	-9999	-0.39	1	1
VEGFR1 homodimer/NRP2	0.027	0.022	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.042	0.006	-9999	-10000	0	0
adherens junction organization	-0.005	0.063	-9999	-0.33	1	1
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	0.046	0.011	-9999	-10000	0	0
FMN1	0.036	0.015	-9999	-10000	0	0
mol:IP3	0.035	0.006	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.032	0.012	-9999	-10000	0	0
CTNNB1	0.012	0	-9999	-10000	0	0
AKT1	0.041	0.008	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.034	0.012	-9999	-10000	0	0
CTNND1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.036	0.011	-9999	-10000	0	0
VASP	0.037	0.011	-9999	-10000	0	0
ZYX	0.037	0.011	-9999	-10000	0	0
JUB	-0.099	0.19	-9999	-0.38	151	151
EGFR(dimer)	0.037	0.015	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin	0.023	0.012	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.036	0.008	-9999	-10000	0	0
PIK3CA	0.013	0.001	-9999	-10000	0	0
PI3K	0.037	0.008	-9999	-10000	0	0
FYN	0.016	0.067	-9999	-10000	0	0
mol:Ca2+	0.035	0.006	-9999	-10000	0	0
JUP	0.011	0.021	-9999	-0.44	1	1
PIK3R1	0.013	0	-9999	-10000	0	0
mol:DAG	0.035	0.006	-9999	-10000	0	0
CDH1	0.012	0	-9999	-10000	0	0
RhoA/GDP	0.046	0.011	-9999	-10000	0	0
establishment of polarity of embryonic epithelium	0.036	0.011	-9999	-10000	0	0
SRC	0.012	0	-9999	-10000	0	0
RAC1	0.012	0	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
EGFR	0.011	0.021	-9999	-0.44	1	1
CASR	0.008	0.072	-9999	-0.36	1	1
RhoA/GTP	0.038	0.006	-9999	-10000	0	0
AKT2	0.041	0.008	-9999	-10000	0	0
actin cable formation	0.041	0.014	-9999	-10000	0	0
apoptosis	-0.039	0.007	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
mol:GDP	0.041	0.012	-9999	-10000	0	0
PIP5K1A	0.037	0.011	-9999	-10000	0	0
PLCG1	0.036	0.006	-9999	-10000	0	0
Rac1/GTP	0.039	0.014	-9999	-10000	0	0
homophilic cell adhesion	0.001	0	-9999	-10000	0	0

×

PLK2 and PLK4 events

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
PLK2	0.006	0.069	-9999	-0.73	4	4
PLK4	0.012	0.001	-9999	-10000	0	0
regulation of centriole replication	0.014	0.053	-9999	-0.55	4	4

×

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

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
MET/RANBP9	0.011	0.061	-10000	0	-0.51	6	6
CRKL	0.028	0.035	-10000	0	-10000	0	0
mol:PIP3	-0.015	0.028	0.4	2	-10000	0	2
AKT1	0.002	0.02	0.3	2	-10000	0	2
PTK2B	0.011	0.021	-10000	0	-0.44	1	1
RAPGEF1	0.032	0.036	-10000	0	-10000	0	0
RANBP10	0.012	0	-10000	0	-10000	0	0
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
HGF/MET/SHIP2	0.014	0.066	-10000	0	-0.47	6	6
MAP3K5	0.015	0.083	-10000	0	-0.37	5	5
HGF/MET/CIN85/CBL/ENDOPHILINS	0.021	0.061	-10000	0	-0.43	6	6
AP1	0.011	0.038	-10000	0	-10000	0	0
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.012	0	-10000	0	-10000	0	0
apoptosis	0.006	0.094	-10000	0	-0.74	7	7
STAT3 (dimer)	0.029	0.041	-10000	0	-10000	0	0
GAB1/CRKL/SHP2/PI3K	0.042	0.033	-10000	0	-10000	0	0
INPP5D	0.011	0.021	-10000	0	-0.44	1	1
CBL/CRK	0.034	0.034	-10000	0	-10000	0	0
PTPN11	0.012	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.012	0	-10000	0	-10000	0	0
PTEN	0.01	0.03	-10000	0	-0.44	2	2
ELK1	-0.002	0.03	0.23	1	-0.26	5	6
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.023	0.026	-10000	0	-10000	0	0
PAK1	0.007	0.018	0.28	2	-10000	0	2
HGF/MET/RANBP10	0.014	0.066	-10000	0	-0.47	6	6
HRAS	0.024	0.053	-10000	0	-0.48	1	1
DOCK1	0.033	0.034	-10000	0	-10000	0	0
GAB1	0.023	0.037	-10000	0	-10000	0	0
CRK	0.028	0.035	-10000	0	-10000	0	0
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.07	-10000	0	-0.42	9	9
JUN	0.012	0	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.007	0.037	-10000	0	-0.24	6	6
PIK3R1	0.012	0	-10000	0	-10000	0	0
cell morphogenesis	0.051	0.041	-10000	0	-10000	0	0
GRB2/SHC	0.021	0.033	-10000	0	-10000	0	0
FOS	0.005	0.055	-10000	0	-0.44	7	7
GLMN	-0.001	0.011	-10000	0	-0.23	1	1
cell motility	-0.002	0.03	0.23	1	-0.26	5	6
HGF/MET/MUC20	0.005	0.066	-10000	0	-0.35	14	14
cell migration	0.021	0.033	-10000	0	-10000	0	0
GRB2	0.012	0	-10000	0	-10000	0	0
CBL	0.012	0	-10000	0	-10000	0	0
MET/RANBP10	0.012	0.059	-10000	0	-0.55	5	5
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.024	0.043	-10000	0	-10000	0	0
MET/MUC20	0.003	0.059	-10000	0	-0.56	5	5
RAP1B	0.037	0.034	-10000	0	-10000	0	0
RAP1A	0.037	0.034	-10000	0	-10000	0	0
HGF/MET/RANBP9	0.013	0.068	-10000	0	-0.47	6	6
RAF1	0.029	0.051	-10000	0	-0.45	1	1
STAT3	0.029	0.041	-10000	0	-10000	0	0
cell proliferation	0.037	0.052	-10000	0	-10000	0	0
RPS6KB1	0.009	0.02	-10000	0	-0.28	1	1
MAPK3	-0.006	0.04	0.66	1	-0.24	5	6
MAPK1	-0.007	0.025	-10000	0	-0.24	5	5
RANBP9	0.011	0.021	-10000	0	-0.44	1	1
MAPK8	0.032	0.065	-10000	0	-10000	0	0
SRC	0.029	0.04	-10000	0	-10000	0	0
PI3K	0.021	0.033	-10000	0	-10000	0	0
MET/Glomulin	0.006	0.054	-10000	0	-0.5	5	5
SOS1	0.012	0	-10000	0	-10000	0	0
MAP2K1	0.034	0.048	-10000	0	-0.42	1	1
MET	0.004	0.077	-10000	0	-0.73	5	5
MAP4K1	0.01	0.088	-10000	0	-0.4	5	5
PTK2	0.012	0	-10000	0	-10000	0	0
MAP2K2	0.034	0.051	-10000	0	-0.4	2	2
BAD	0.006	0.021	0.28	2	-10000	0	2
MAP2K4	0.02	0.079	-10000	0	-0.34	5	5
SHP2/GRB2/SOS1/GAB1	-0.006	0.034	-10000	0	-10000	0	0
INPPL1	0.012	0	-10000	0	-10000	0	0
PXN	0.012	0	-10000	0	-10000	0	0
SH3KBP1	0.012	0	-10000	0	-10000	0	0
HGS	0.013	0.034	-10000	0	-0.22	5	5
PLCgamma1/PKC	0.009	0	-10000	0	-10000	0	0
HGF	0.003	0.068	-10000	0	-0.47	9	9
RASA1	0.012	0.001	-10000	0	-10000	0	0
NCK1	0.012	0	-10000	0	-10000	0	0
PTPRJ	0.012	0	-10000	0	-10000	0	0
NCK/PLCgamma1	0.023	0.035	-10000	0	-10000	0	0
PDPK1	-0.006	0.022	0.33	2	-10000	0	2
HGF/MET/SHIP	0.013	0.068	-10000	0	-0.47	6	6

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	-0.009	0.01	0.19	1	-10000	0	1
BUB1B	0.017	0.02	-10000	0	-10000	0	0
PLK1	0.014	0.01	-10000	0	-10000	0	0
PLK1S1	0.012	0.009	-10000	0	-0.14	1	1
KIF2A	0.02	0.009	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	0.014	0.01	-10000	0	-10000	0	0
GOLGA2	0.012	0	-10000	0	-10000	0	0
Hec1/SPC24	0.019	0.06	-10000	0	-0.4	9	9
WEE1	0.017	0.023	-10000	0	-10000	0	0
cytokinesis	0.027	0.017	-10000	0	-10000	0	0
PP2A-alpha B56	0.03	0.013	-10000	0	-10000	0	0
AURKA	0.013	0.007	-10000	0	-10000	0	0
PICH/PLK1	0.008	0.092	-10000	0	-0.33	31	31
CENPE	0.019	0.023	-10000	0	-0.43	1	1
RhoA/GTP	0.009	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.02	0.009	-10000	0	-10000	0	0
PPP2CA	0.012	0	-10000	0	-10000	0	0
FZR1	0.011	0.021	-10000	0	-0.44	1	1
TPX2	0.011	0.016	-10000	0	-0.14	4	4
PAK1	0.012	0.001	-10000	0	-10000	0	0
SPC24	-0.002	0.1	-10000	0	-0.73	9	9
FBXW11	0.012	0	-10000	0	-10000	0	0
CLSPN	0.013	0.01	-10000	0	-0.16	1	1
GORASP1	0.012	0	-10000	0	-10000	0	0
metaphase	0	0.001	-10000	0	-0.011	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.008	0.006	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0.001	-10000	0	-10000	0	0
STAG2	0.012	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.002	0.007	-10000	0	-10000	0	0
spindle elongation	0.014	0.01	-10000	0	-10000	0	0
ODF2	0.012	0.001	-10000	0	-10000	0	0
BUB1	-0.002	0.009	-10000	0	-10000	0	0
TPT1	0.013	0.006	-10000	0	-10000	0	0
CDC25C	0.015	0.005	-10000	0	-10000	0	0
CDC25B	-0.031	0.17	-10000	0	-0.72	27	27
SGOL1	0.009	0.01	-10000	0	-0.19	1	1
RHOA	0.012	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.019	0.077	-10000	0	-0.33	27	27
CDC14B	0.009	0.015	-10000	0	-0.31	1	1
CDC20	0.012	0	-10000	0	-10000	0	0
PLK1/PBIP1	0.016	0.013	-10000	0	-0.2	1	1
mitosis	0	0.001	-10000	0	-10000	0	0
FBXO5	0.016	0.017	-10000	0	-10000	0	0
CDC2	0	0.004	-10000	0	-0.014	27	27
NDC80	0.012	0.001	-10000	0	-10000	0	0
metaphase plate congression	0.013	0.006	-10000	0	-10000	0	0
ERCC6L	0.008	0.087	-10000	0	-0.31	31	31
NLP/gamma Tubulin	0.011	0.007	-10000	0	-10000	0	0
microtubule cytoskeleton organization	0.013	0.006	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-10000	0	-10000	0	0
PPP1R12A	0.01	0.03	-10000	0	-0.44	2	2
interphase	0	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	0.027	0.008	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	0.031	0.007	-10000	0	-10000	0	0
RAB1A	0.012	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.016	0.008	-10000	0	-10000	0	0
mitotic prometaphase	0	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.03	0.013	-10000	0	-10000	0	0
microtubule-based process	0.02	0.009	-10000	0	-10000	0	0
Golgi organization	0.014	0.01	-10000	0	-10000	0	0
Cohesin/SA2	0.017	0.008	-10000	0	-10000	0	0
PPP1CB/MYPT1	0.016	0.031	-10000	0	-0.44	2	2
KIF20A	0.012	0	-10000	0	-10000	0	0
APC/C/CDC20	0.02	0.009	-10000	0	-10000	0	0
PPP2R1A	0.012	0	-10000	0	-10000	0	0
chromosome segregation	0.016	0.012	-10000	0	-0.2	1	1
PRC1	0.012	0	-10000	0	-10000	0	0
ECT2	0.016	0.04	-10000	0	-0.39	4	4
C13orf34	0.017	0.008	-10000	0	-10000	0	0
NUDC	0.013	0.006	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.017	0.019	-10000	0	-10000	0	0
spindle assembly	0.014	0.008	-10000	0	-10000	0	0
spindle stabilization	0.012	0.009	-10000	0	-0.14	1	1
APC/C/HCDH1	0.015	0.018	-10000	0	-0.25	2	2
MKLP2/PLK1	0.02	0.009	-10000	0	-10000	0	0
CCNB1	0.012	0.003	-10000	0	-10000	0	0
PPP1CB	0.011	0.021	-10000	0	-0.44	1	1
BTRC	0.012	0	-10000	0	-10000	0	0
ROCK2	0.019	0.03	-10000	0	-0.42	2	2
TUBG1	0.013	0.006	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.019	0.075	-10000	0	-0.32	27	27
MLF1IP	0.009	0.015	-10000	0	-0.31	1	1
INCENP	0.012	0	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.01	0.03	-9999	-0.44	2	2
positive regulation of NF-kappaB transcription factor activity	0.017	0.021	-9999	-0.3	2	2
MAP2K4	0.037	0.026	-9999	-10000	0	0
IKBKB	0.012	0	-9999	-10000	0	0
TNFRSF10B	0.012	0	-9999	-10000	0	0
TNFRSF10A	0.012	0	-9999	-10000	0	0
SMPD1	0.012	0.044	-9999	-0.38	5	5
IKBKG	0.011	0.021	-9999	-0.44	1	1
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.012	0	-9999	-10000	0	0
TRAIL/TRAILR2	0.017	0.021	-9999	-0.3	2	2
TRAIL/TRAILR3	-0.018	0.14	-9999	-0.54	30	30
TRAIL/TRAILR1	0.017	0.021	-9999	-0.3	2	2
TRAIL/TRAILR4	0.017	0.021	-9999	-0.3	2	2
TRAIL/TRAILR1/DAP3/GTP	0.023	0.016	-9999	-10000	0	0
IKK complex	-0.001	0.016	-9999	-0.32	1	1
RIPK1	0.012	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0.009	0	-9999	-10000	0	0
MAPK3	0.017	0.026	-9999	-0.3	3	3
MAP3K1	0.034	0.02	-9999	-10000	0	0
TRAILR4 (trimer)	0.012	0	-9999	-10000	0	0
TRADD	0.012	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.012	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.031	0.019	-9999	-10000	0	0
CFLAR	0.012	0	-9999	-10000	0	0
MAPK1	0.018	0.021	-9999	-0.3	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP	0.036	0.015	-9999	-10000	0	0
mol:ceramide	0.012	0.044	-9999	-0.38	5	5
FADD	0.012	0	-9999	-10000	0	0
MAPK8	0.041	0.025	-9999	-10000	0	0
TRAF2	0.011	0.021	-9999	-0.44	1	1
TRAILR3 (trimer)	-0.033	0.18	-9999	-0.73	28	28
CHUK	0.012	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	0.024	0.018	-9999	-10000	0	0
DAP3	0.012	0	-9999	-10000	0	0
CASP10	-0.001	0.017	-9999	-10000	0	0
JNK cascade	0.017	0.021	-9999	-0.3	2	2
TRAIL (trimer)	0.01	0.03	-9999	-0.44	2	2
TNFRSF10C	-0.033	0.18	-9999	-0.73	28	28
TRAIL/TRAILR1/DAP3/GTP/FADD	0.028	0.015	-9999	-10000	0	0
TRAIL/TRAILR2/FADD	0.024	0.018	-9999	-10000	0	0
cell death	0.012	0.044	-9999	-0.38	5	5
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.031	0.019	-9999	-10000	0	0
TRAILR2 (trimer)	0.012	0	-9999	-10000	0	0
CASP8	0	0.007	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.036	0.015	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.012	0	-9999	-10000	0	0
Rac1/GDP	0.002	0.008	-9999	-10000	0	0
DOCK1	0.012	0	-9999	-10000	0	0
ITGA4	-0.005	0.087	-9999	-0.44	18	18
RAC1	0.012	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.007	0.094	-9999	-0.33	33	33
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.012	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.014	0.053	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.01	0.073	-9999	-0.44	4	4
lamellipodium assembly	0.001	0.014	-9999	-10000	0	0
PIK3CA	0.012	0.001	-9999	-10000	0	0
PI3K	0.018	0	-9999	-10000	0	0
ARF6	0.012	0	-9999	-10000	0	0
TLN1	0.012	0	-9999	-10000	0	0
PXN	0.019	0	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
ARF6/GTP	-0.007	0.035	-9999	-10000	0	0
cell adhesion	0.026	0.044	-9999	-10000	0	0
CRKL/CBL	0.018	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.02	0.048	-9999	-10000	0	0
ITGB1	0.012	0	-9999	-10000	0	0
ITGB7	-0.006	0.089	-9999	-0.44	19	19
ARF6/GDP	0.002	0.008	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.022	0.069	-9999	-0.41	8	8
p130Cas/Crk/Dock1	0.025	0.013	-9999	-10000	0	0
VCAM1	0.001	0.069	-9999	-0.44	11	11
alpha4/beta1 Integrin/Paxillin/Talin	0.027	0.045	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.027	0.046	-9999	-10000	0	0
BCAR1	0.011	0.021	-9999	-0.44	1	1
mol:GDP	-0.026	0.046	-9999	-10000	0	0
CBL	0.012	0	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
GIT1	0.011	0.021	-9999	-0.44	1	1
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.027	0.045	-9999	-10000	0	0
Rac1/GTP	0.002	0.015	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.041	0.049	-10000	0	-10000	0	0
UGCG	0.022	0.018	-10000	0	-10000	0	0
AKT1/mTOR/p70S6K/Hsp90/TERT	0.038	0.087	-10000	0	-0.33	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.022	0.018	-10000	0	-10000	0	0
mol:DAG	0.002	0.02	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.024	0.08	-10000	0	-0.44	4	4
FRAP1	0.046	0.12	-10000	0	-0.51	4	4
FOXO3	0.056	0.08	-10000	0	-10000	0	0
AKT1	0.052	0.084	-10000	0	-0.38	2	2
GAB2	0.013	0.002	-10000	0	-10000	0	0
SMPD1	0.015	0.07	-10000	0	-0.62	5	5
SGMS1	0.022	0.018	-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	0.005	-10000	0	-10000	0	0
CALM1	0.012	0	-10000	0	-10000	0	0
cell proliferation	0.038	0.043	-10000	0	-10000	0	0
EIF3A	0.012	0	-10000	0	-10000	0	0
PI3K	0.022	0.006	-10000	0	-10000	0	0
RPS6KB1	0.022	0.039	-10000	0	-0.73	1	1
mol:sphingomyelin	0.002	0.02	-10000	0	-10000	0	0
natural killer cell activation	0	0.002	-10000	0	-10000	0	0
JAK3	0.013	0.035	-10000	0	-0.73	1	1
PIK3R1	0.015	0.002	-10000	0	-10000	0	0
JAK1	0.014	0.021	-10000	0	-0.43	1	1
NFKB1	0.012	0	-10000	0	-10000	0	0
MYC	0.053	0.092	-10000	0	-10000	0	0
MYB	0.024	0.064	-10000	0	-1.2	1	1
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.049	0.071	-10000	0	-0.42	2	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.033	0.041	-10000	0	-0.52	2	2
mol:PI-3-4-5-P3	0.049	0.07	-10000	0	-0.41	2	2
Rac1/GDP	0.024	0.006	-10000	0	-10000	0	0
T cell proliferation	0.053	0.066	-10000	0	-0.38	2	2
SHC1	0.013	0.002	-10000	0	-10000	0	0
RAC1	0.012	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.005	0.003	-10000	0	-0.066	1	1
PRKCZ	0.053	0.068	-10000	0	-0.4	2	2
NF kappa B1 p50/RelA	0.053	0.1	-10000	0	-0.44	4	4
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.036	0.054	-10000	0	-0.39	2	2
HSP90AA1	0.012	0	-10000	0	-10000	0	0
RELA	0.012	0	-10000	0	-10000	0	0
IL2RA	0.002	0.069	-10000	0	-0.44	11	11
IL2RB	0.002	0.075	-10000	0	-0.44	13	13
TERT	-0.058	0.22	-10000	0	-0.72	44	44
E2F1	0.021	0.041	-10000	0	-0.41	2	2
SOS1	0.013	0.002	-10000	0	-10000	0	0
RPS6	0.011	0.035	-10000	0	-0.73	1	1
mol:cAMP	-0.002	0.002	0.031	1	-10000	0	1
PTPN11	0.013	0.003	-10000	0	-10000	0	0
IL2RG	0.013	0.03	-10000	0	-0.44	2	2
actin cytoskeleton organization	0.053	0.066	-10000	0	-0.38	2	2
GRB2	0.013	0.002	-10000	0	-10000	0	0
IL2	0.006	0.006	-10000	0	-10000	0	0
PIK3CA	0.015	0.002	-10000	0	-10000	0	0
Rac1/GTP	0.032	0.008	-10000	0	-10000	0	0
LCK	0.001	0.096	-10000	0	-0.66	9	9
BCL2	0.027	0.2	-10000	0	-0.83	22	22

×

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

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
BAG4	0.012	0.001	-9999	-10000	0	0
Caspase 8 (4 units)	0.022	0.06	-9999	-0.38	1	1
NEF	-0.006	0.038	-9999	-10000	0	0
NFKBIA	0.013	0.013	-9999	-10000	0	0
BIRC3	0.028	0.069	-9999	-0.49	8	8
CYCS	0.022	0.071	-9999	-0.37	2	2
RIPK1	0.012	0	-9999	-10000	0	0
CD247	-0.009	0.1	-9999	-0.52	15	15
MAP2K7	0.03	0.062	-9999	-0.64	1	1
protein ubiquitination	0.056	0.021	-9999	-10000	0	0
CRADD	0.012	0	-9999	-10000	0	0
DAXX	0.012	0	-9999	-10000	0	0
FAS	0.006	0.051	-9999	-0.44	6	6
BID	0.018	0.073	-9999	-0.4	2	2
NF-kappa-B/RelA/I kappa B alpha	0.03	0.037	-9999	-0.31	1	1
TRADD	0.012	0	-9999	-10000	0	0
MAP3K5	0.012	0	-9999	-10000	0	0
CFLAR	0.012	0	-9999	-10000	0	0
FADD	0.012	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.03	0.037	-9999	-0.31	1	1
MAPK8	0.035	0.059	-9999	-0.6	1	1
APAF1	0.012	0.001	-9999	-10000	0	0
TRAF1	0.012	0	-9999	-10000	0	0
TRAF2	0.011	0.021	-9999	-0.44	1	1
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.013	0.075	-9999	-0.37	2	2
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.051	0.024	-9999	-10000	0	0
CHUK	0.057	0.022	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.034	0.026	-9999	-10000	0	0
TCRz/NEF	-0.011	0.1	-9999	-0.35	36	36
TNF	0.01	0.03	-9999	-0.44	2	2
FASLG	-0.019	0.16	-9999	-0.59	30	30
NFKB1	0.013	0.013	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.024	0.018	-9999	-10000	0	0
CASP6	0.037	0.044	-9999	-10000	0	0
CASP7	0.05	0.082	-9999	-0.46	7	7
RELA	0.013	0.013	-9999	-10000	0	0
CASP2	0.012	0	-9999	-10000	0	0
CASP3	0.05	0.081	-9999	-0.46	7	7
TNFRSF1A	0.012	0	-9999	-10000	0	0
TNFR1A/BAG4	0.018	0.001	-9999	-10000	0	0
CASP8	0.012	0	-9999	-10000	0	0
CASP9	0.012	0	-9999	-10000	0	0
MAP3K14	0.054	0.023	-9999	-10000	0	0
APAF-1/Caspase 9	-0.016	0.055	-9999	-0.43	3	3
BCL2	0.03	0.072	-9999	-0.54	1	1

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.013	0	-9999	-10000	0	0
ELF1	0.012	0.051	-9999	-0.31	11	11
CCNA2	0.012	0	-9999	-10000	0	0
PIK3CA	0.013	0.001	-9999	-10000	0	0
JAK3	0.011	0.035	-9999	-0.73	1	1
PIK3R1	0.013	0	-9999	-10000	0	0
JAK1	0.012	0.021	-9999	-0.44	1	1
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.053	0.062	-9999	-0.47	2	2
SHC1	0.013	0	-9999	-10000	0	0
SP1	0.016	0.034	-9999	-0.31	4	4
IL2RA	0.011	0.11	-9999	-0.68	11	11
IL2RB	0	0.075	-9999	-0.44	13	13
SOS1	0.013	0	-9999	-10000	0	0
IL2RG	0.011	0.03	-9999	-0.44	2	2
G1/S transition of mitotic cell cycle	0.033	0.063	-9999	-0.61	4	4
PTPN11	0.013	0	-9999	-10000	0	0
CCND2	0.019	0.072	-9999	-0.66	5	5
LCK	0	0.096	-9999	-0.66	9	9
GRB2	0.013	0	-9999	-10000	0	0
IL2	0.004	0.005	-9999	-10000	0	0
CDK6	0.012	0	-9999	-10000	0	0
CCND3	0.057	0.056	-9999	-10000	0	0

×

Insulin 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
CBL/APS/CAP	-0.008	0.045	-9999	-0.38	4	4
TC10/GTP	-0.008	0.044	-9999	-0.36	4	4
Insulin Receptor/Insulin/IRS1/Shp2	0.027	0	-9999	-10000	0	0
HRAS	0.011	0.021	-9999	-0.44	1	1
APS homodimer	0.006	0.069	-9999	-0.73	4	4
GRB14	-0.025	0.14	-9999	-0.52	31	31
FOXO3	-0.004	0.12	-9999	-0.54	21	21
AKT1	0.024	0.066	-9999	-10000	0	0
INSR	0.014	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0.032	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.012	0	-9999	-10000	0	0
SORBS1	0.001	0.072	-9999	-0.44	12	12
CRK	0.012	0	-9999	-10000	0	0
PTPN1	0.028	0	-9999	-10000	0	0
CAV1	0.021	0.022	-9999	-10000	0	0
CBL/APS/CAP/Crk-II/C3G	0.026	0.056	-9999	-0.4	4	4
Insulin Receptor/Insulin/IRS1/NCK2	0.027	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
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.033	0	-9999	-10000	0	0
RPS6KB1	0.028	0.063	-9999	-10000	0	0
PARD6A	0.006	0.069	-9999	-0.73	4	4
CBL	0.012	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	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.013	0.05	-9999	-10000	0	0
HRAS/GTP	-0.001	0.01	-9999	-10000	0	0
Insulin Receptor	0.014	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.032	0	-9999	-10000	0	0
PRKCI	-0.005	0.032	-9999	-0.43	2	2
Insulin Receptor/Insulin/GRB14/PDK1	-0.015	0.061	-9999	-10000	0	0
SHC1	0.012	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0.024	0.001	-9999	-10000	0	0
PI3K	0.027	0	-9999	-10000	0	0
NCK2	0.012	0	-9999	-10000	0	0
RHOQ	0.012	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0.008	0.015	-9999	-0.31	1	1
AKT2	0.024	0.066	-9999	-10000	0	0
PRKCZ	-0.003	0.014	-9999	-10000	0	0
SH2B2	0.006	0.069	-9999	-0.73	4	4
SHC/SHIP	0.029	0.01	-9999	-10000	0	0
F2RL2	-0.041	0.19	-9999	-0.7	34	34
TRIP10	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0.018	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.017	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.032	0	-9999	-10000	0	0
RAPGEF1	0.011	0.021	-9999	-0.44	1	1
RASA1	0.012	0.001	-9999	-10000	0	0
NCK1	0.012	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	0.021	0.058	-9999	-0.43	4	4
TC10/GDP	0.009	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.027	0	-9999	-10000	0	0
INPP5D	0.022	0.011	-9999	-10000	0	0
SOS1	0.012	0	-9999	-10000	0	0
SGK1	-0.038	0.17	-9999	-0.8	21	21
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.012	0	-9999	-10000	0	0
IRS1	0.012	0	-9999	-10000	0	0
p62DOK/RasGAP	0.024	0.001	-9999	-10000	0	0
INS	0.003	0	-9999	-10000	0	0
mol:PI-3-4-P2	0.022	0.011	-9999	-10000	0	0
GRB2	0.012	0	-9999	-10000	0	0
EIF4EBP1	0.027	0.066	-9999	-10000	0	0
PTPRA	0.014	0	-9999	-10000	0	0
PIK3CA	0.012	0.001	-9999	-10000	0	0
TC10/GTP/CIP4	0.017	0	-9999	-10000	0	0
PDPK1	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.029	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.018	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS3	0.012	0	-9999	-10000	0	0
Par3/Par6	-0.006	0.12	-9999	-0.41	35	35

×

p38 MAPK signaling pathway

Figure S113. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S113. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.013	0	-10000	0	-10000	0	0
TRAF2/ASK1	0.016	0.013	-10000	0	-0.25	1	1
ATM	0.012	0	-10000	0	-10000	0	0
MAP2K3	0.029	0.026	-10000	0	-0.32	1	1
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.034	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	0.008	0.053	-10000	0	-0.63	3	3
TXN	0.007	0	-10000	0	-10000	0	0
CALM1	0.012	0	-10000	0	-10000	0	0
GADD45A	0.012	0	-10000	0	-10000	0	0
GADD45B	0.012	0	-10000	0	-10000	0	0
MAP3K1	0.011	0.021	-10000	0	-0.44	1	1
MAP3K6	0.01	0.03	-10000	0	-0.44	2	2
MAP3K7	0.012	0	-10000	0	-10000	0	0
MAP3K4	0.012	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.017	0.021	-10000	0	-0.3	2	2
TAK1/TAB family	0.001	0.011	0.17	2	-10000	0	2
RAC1/OSM/MEKK3	0.023	0.011	-10000	0	-10000	0	0
TRAF2	0.011	0.021	-10000	0	-0.44	1	1
RAC1/OSM/MEKK3/MKK3	-0.002	0.016	-10000	0	-10000	0	0
TRAF6	0.007	0	-10000	0	-10000	0	0
RAC1	0.012	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.027	0.13	-10000	0	-0.48	35	35
CCM2	0.011	0.021	-10000	0	-0.44	1	1
CaM/Ca2+/CAMKIIB	-0.007	0.083	-10000	0	-0.28	35	35
MAPK11	0.009	0.049	-10000	0	-0.73	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.002	0.076	-10000	0	-0.44	5	5
OSM/MEKK3	0.018	0.015	-10000	0	-0.3	1	1
TAOK1	0.015	0	-10000	0	-10000	0	0
TAOK2	0.015	0	-10000	0	-10000	0	0
TAOK3	0.015	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.012	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.012	0	-10000	0	-10000	0	0
MAP3K10	0.012	0	-10000	0	-10000	0	0
MAP3K3	0.012	0	-10000	0	-10000	0	0
TRX/ASK1	0.015	0	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	0.027	0.031	-10000	0	-0.41	2	2

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.032	0.017	-10000	0	-10000	0	0
regulation of axonogenesis	-0.024	0.008	-10000	0	-10000	0	0
myoblast fusion	-0.022	0.016	-10000	0	-10000	0	0
mol:GTP	0.01	0.004	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.003	0.11	0.56	10	-10000	0	10
ARF1/GTP	0.016	0.006	-10000	0	-10000	0	0
mol:GM1	0.009	0.003	-10000	0	-10000	0	0
mol:Choline	0.024	0.012	-10000	0	-10000	0	0
lamellipodium assembly	0.009	0.027	-10000	0	-10000	0	0
MAPK3	0.022	0.016	-10000	0	-0.27	1	1
ARF6/GTP/NME1/Tiam1	-0.002	0.11	-10000	0	-0.56	10	10
ARF1	0.012	0	-10000	0	-10000	0	0
ARF6/GDP	0.022	0.016	-10000	0	-10000	0	0
ARF1/GDP	0.03	0.018	-10000	0	-10000	0	0
ARF6	0.012	0.001	-10000	0	-10000	0	0
RAB11A	0.012	0	-10000	0	-10000	0	0
TIAM1	-0.028	0.13	-10000	0	-0.44	43	43
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.023	0.008	-10000	0	-10000	0	0
actin filament bundle formation	-0.021	0.009	-10000	0	-10000	0	0
KALRN	0.007	0.025	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	0.018	0	-10000	0	-10000	0	0
RhoA/GDP	0.022	0.009	-10000	0	-10000	0	0
NME1	-0.003	0.11	-10000	0	-0.73	10	10
Rac1/GDP	0.022	0.009	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.01	0.004	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.009	0.027	-10000	0	-10000	0	0
RAC1	0.012	0	-10000	0	-10000	0	0
liver development	0.01	0.004	-10000	0	-10000	0	0
ARF6/GTP	0.01	0.004	-10000	0	-10000	0	0
RhoA/GTP	0.016	0.006	-10000	0	-10000	0	0
mol:GDP	0.009	0.027	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0.022	0.008	-10000	0	-10000	0	0
RHOA	0.012	0	-10000	0	-10000	0	0
PLD1	0.018	0.014	-10000	0	-0.28	1	1
RAB11FIP3	0.012	0	-10000	0	-10000	0	0
tube morphogenesis	0.009	0.027	-10000	0	-10000	0	0
ruffle organization	0.024	0.008	-10000	0	-10000	0	0
regulation of epithelial cell migration	0.01	0.004	-10000	0	-10000	0	0
PLD2	0.019	0.002	-10000	0	-10000	0	0
PIP5K1A	0.024	0.008	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.024	0.012	-10000	0	-10000	0	0
Rac1/GTP	0.009	0.027	-10000	0	-10000	0	0

×

ceramide signaling 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
MAP4K4	0.04	0.039	-10000	0	-10000	0	0
BAG4	0.012	0.001	-10000	0	-10000	0	0
BAD	0.025	0.025	-10000	0	-0.39	1	1
NFKBIA	0.012	0	-10000	0	-10000	0	0
BIRC3	0.004	0.065	-10000	0	-0.47	8	8
BAX	0.025	0.019	-10000	0	-0.19	1	1
EnzymeConsortium:3.1.4.12	0.013	0.01	-10000	0	-10000	0	0
IKBKB	0.044	0.037	-10000	0	-10000	0	0
MAP2K2	0.035	0.022	-10000	0	-0.32	1	1
MAP2K1	0.035	0.017	-10000	0	-10000	0	0
SMPD1	0.015	0.025	-10000	0	-0.21	5	5
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.045	0.038	-10000	0	-10000	0	0
MAP2K4	0.029	0.027	-10000	0	-0.24	1	1
protein ubiquitination	0.045	0.039	-10000	0	-10000	0	0
EnzymeConsortium:2.7.1.37	0.039	0.02	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.031	0.018	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
mol:ceramide	0.02	0.02	-10000	0	-0.2	1	1
I-kappa-B-alpha/RELA/p50/ubiquitin	0.017	0	-10000	0	-10000	0	0
MADD	0.013	0	-10000	0	-10000	0	0
MAP3K1	0.025	0.022	-10000	0	-0.26	1	1
TRADD	0.013	0	-10000	0	-10000	0	0
RELA/p50	0.012	0	-10000	0	-10000	0	0
MAPK3	0.037	0.019	-10000	0	-10000	0	0
MAPK1	0.037	0.019	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0.018	0	-10000	0	-10000	0	0
FADD	0.04	0.039	-10000	0	-10000	0	0
KSR1	0.026	0.019	-10000	0	-10000	0	0
MAPK8	0.033	0.025	-10000	0	-10000	0	0
TRAF2	0.011	0.021	-10000	0	-0.44	1	1
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.044	0.037	-10000	0	-10000	0	0
TNF R/SODD	0.018	0.001	-10000	0	-10000	0	0
TNF	0.011	0.03	-10000	0	-0.44	2	2
CYCS	0.03	0.028	0.13	19	-0.29	1	20
IKBKG	0.043	0.041	-10000	0	-0.43	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.035	0.04	-10000	0	-10000	0	0
RELA	0.012	0	-10000	0	-10000	0	0
RIPK1	0.012	0	-10000	0	-10000	0	0
AIFM1	0.03	0.029	-10000	0	-0.29	1	1
TNF/TNF R/SODD	0.024	0.018	-10000	0	-10000	0	0
TNFRSF1A	0.012	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.027	0.011	-10000	0	-10000	0	0
NSMAF	0.04	0.038	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
BCL2	-0.009	0.096	-10000	0	-0.44	22	22

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.015	0.033	-9999	-0.3	5	5
AKT1	0.071	0.03	-9999	-0.47	1	1
PTK2B	0.043	0.039	-9999	-0.47	1	1
VEGFR2 homodimer/Frs2	0.031	0.029	-9999	-0.58	1	1
CAV1	0.008	0.042	-9999	-0.44	4	4
CALM1	0.012	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.038	0.034	-9999	-0.47	2	2
endothelial cell proliferation	0.046	0.069	-9999	-0.48	1	1
mol:Ca2+	0.045	0.032	-9999	-0.48	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.044	0.033	-9999	-0.5	1	1
RP11-342D11.1	0.037	0.032	-9999	-0.49	1	1
CDH5	0.012	0	-9999	-10000	0	0
VEGFA homodimer	0.031	0.024	-9999	-0.43	1	1
SHC1	0.012	0	-9999	-10000	0	0
SHC2	0	0.087	-9999	-0.6	9	9
HRAS/GDP	-0.002	0.025	-9999	-10000	0	0
SH2D2A	0.012	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.063	0.044	-9999	-0.56	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.038	0.034	-9999	-0.47	2	2
VEGFR1 homodimer	0.012	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.002	0.027	-9999	-10000	0	0
GRB10	0.046	0.032	-9999	-0.48	1	1
PTPN11	0.012	0	-9999	-10000	0	0
GRB2	0.012	0	-9999	-10000	0	0
PAK1	0.012	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.048	0.031	-9999	-0.48	1	1
HRAS	0.011	0.021	-9999	-0.44	1	1
VEGF/Rho/ROCK1/Integrin Complex	0.04	0.045	-9999	-0.8	1	1
HIF1A	0.012	0	-9999	-10000	0	0
FRS2	0.012	0.001	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.043	0.032	-9999	-0.49	1	1
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.008	0.042	-9999	-0.44	4	4
Nck/Pak	0.018	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.038	0.034	-9999	-0.47	2	2
mol:GDP	-0.002	0.026	-9999	-10000	0	0
mol:NADP	0.059	0.042	-9999	-0.51	1	1
eNOS/Hsp90	0.062	0.04	-9999	-0.48	1	1
PIK3R1	0.012	0	-9999	-10000	0	0
mol:IP3	0.045	0.032	-9999	-0.49	1	1
HIF1A/ARNT	0.018	0.015	-9999	-10000	0	0
SHB	0.012	0	-9999	-10000	0	0
VEGFA	0.013	0.035	-9999	-0.73	1	1
VEGFC	0.006	0.058	-9999	-0.48	6	6
FAK1/Vinculin	0.058	0.042	-9999	-0.65	1	1
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.042	0.04	-9999	-0.5	1	1
PTPN6	0.012	0	-9999	-10000	0	0
EPAS1	0.021	0.015	-9999	-10000	0	0
mol:L-citrulline	0.059	0.042	-9999	-0.51	1	1
ITGAV	0.012	0	-9999	-10000	0	0
PIK3CA	0.012	0.001	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.044	0.033	-9999	-0.5	1	1
VEGFR2 homodimer/VEGFA homodimer	0.043	0.034	-9999	-0.53	1	1
VEGFR2/3 heterodimer	0.028	0.038	-9999	-0.58	1	1
VEGFB	0.012	0	-9999	-10000	0	0
MAPK11	0.046	0.034	-9999	-0.51	1	1
VEGFR2 homodimer	0.029	0.033	-9999	-0.67	1	1
FLT1	0.012	0	-9999	-10000	0	0
NEDD4	0.014	0.001	-9999	-10000	0	0
MAPK3	0.025	0.05	-9999	-0.44	1	1
MAPK1	0.025	0.05	-9999	-0.44	1	1
VEGFA145/NRP2	0.016	0.037	-9999	-0.36	4	4
VEGFR1/2 heterodimer	0.031	0.029	-9999	-0.58	1	1
KDR	0.029	0.033	-9999	-0.67	1	1
VEGFA165/NRP1/VEGFR2 homodimer	0.045	0.036	-9999	-0.48	1	1
SRC	0.012	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.028	0.049	-9999	-0.45	1	1
PI3K	0.064	0.033	-9999	-0.51	1	1
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.038	0.034	-9999	-0.47	2	2
FES	0.045	0.036	-9999	-0.5	1	1
GAB1	0.055	0.031	-9999	-0.52	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	0.038	0.034	-9999	-0.47	2	2
CTNNB1	0.012	0	-9999	-10000	0	0
SOS1	0.012	0	-9999	-10000	0	0
ARNT	0.011	0.021	-9999	-0.44	1	1
eNOS/Caveolin-1	0.061	0.043	-9999	-0.48	1	1
VEGFR2 homodimer/VEGFA homodimer/Yes	0.038	0.042	-9999	-0.58	2	2
PI3K/GAB1	0.074	0.03	-9999	-0.48	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.048	0.031	-9999	-0.48	1	1
PRKACA	0.012	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.031	0.05	-9999	-0.46	3	3
HSP90AA1	0.012	0	-9999	-10000	0	0
CDC42	0.045	0.034	-9999	-0.5	1	1
actin cytoskeleton reorganization	0.038	0.034	-9999	-0.47	2	2
PTK2	0.053	0.045	-9999	-0.7	1	1
EDG1	0.037	0.032	-9999	-0.49	1	1
mol:DAG	0.045	0.032	-9999	-0.49	1	1
CaM/Ca2+	0.048	0.03	-9999	-0.45	1	1
MAP2K3	0.049	0.031	-9999	-0.47	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.049	0.033	-9999	-0.5	1	1
PLCG1	0.046	0.032	-9999	-0.5	1	1
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.044	0.033	-9999	-0.5	1	1
IQGAP1	0.012	0	-9999	-10000	0	0
YES1	0.011	0.021	-9999	-0.44	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.038	0.034	-9999	-0.47	2	2
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.038	0.034	-9999	-0.47	2	2
cell migration	0.075	0.038	-9999	-0.55	1	1
mol:PI-3-4-5-P3	0.062	0.031	-9999	-0.48	1	1
FYN	0.012	0	-9999	-10000	0	0
VEGFB/NRP1	0.043	0.03	-9999	-0.46	1	1
mol:NO	0.059	0.042	-9999	-0.51	1	1
PXN	0.012	0	-9999	-10000	0	0
HRAS/GTP	-0.002	0.025	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.048	0.033	-9999	-0.5	1	1
VHL	0.012	0	-9999	-10000	0	0
ITGB3	0.007	0.047	-9999	-0.44	5	5
NOS3	0.061	0.046	-9999	-0.59	1	1
VEGFR2 homodimer/VEGFA homodimer/Sck	0.031	0.063	-9999	-0.44	7	7
RAC1	0.012	0	-9999	-10000	0	0
PRKCA	0.049	0.03	-9999	-0.46	1	1
PRKCB	-0.001	0.096	-9999	-0.46	1	1
VCL	0.012	0	-9999	-10000	0	0
VEGFA165/NRP1	0.039	0.032	-9999	-0.49	1	1
VEGFR1/2 heterodimer/VEGFA homodimer	0.038	0.034	-9999	-0.47	2	2
VEGFA165/NRP2	0.016	0.037	-9999	-0.36	4	4
MAPKKK cascade	0.063	0.03	-9999	-10000	0	0
NRP2	0.009	0.036	-9999	-0.44	3	3
VEGFC homodimer	0.006	0.058	-9999	-0.48	6	6
NCK1	0.012	0	-9999	-10000	0	0
ROCK1	0.011	0.021	-9999	-0.44	1	1
FAK1/Paxillin	0.058	0.042	-9999	-0.65	1	1
MAP3K13	0.046	0.033	-9999	-0.5	1	1
PDPK1	0.065	0.028	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.036	0.004	-9999	-10000	0	0
KLHL20	-0.013	0.042	-9999	-0.24	4	4
CYFIP2	0.011	0.021	-9999	-0.44	1	1
Rac1/GDP	0.051	0.022	-9999	-10000	0	0
ENAH	0.036	0.004	-9999	-10000	0	0
AP1M1	0.012	0	-9999	-10000	0	0
RAP1B	0.012	0	-9999	-10000	0	0
RAP1A	0.012	0	-9999	-10000	0	0
CTNNB1	0.012	0	-9999	-10000	0	0
CDC42/GTP	-0.001	0.009	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.009	0.029	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.022	0.049	-9999	-10000	0	0
RAPGEF1	0.044	0.01	-9999	-10000	0	0
CTNND1	0.012	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.03	0.004	-9999	-10000	0	0
CRK	0.04	0.003	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	0.025	0.013	-9999	-10000	0	0
alphaE/beta7 Integrin	0.005	0.064	-9999	-10000	0	0
IQGAP1	0.012	0	-9999	-10000	0	0
NCKAP1	0.012	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.023	0.011	-9999	-10000	0	0
DLG1	0.035	0.01	-9999	-10000	0	0
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0.006	-9999	-10000	0	0
MLLT4	0.011	0.021	-9999	-0.44	1	1
ARF6/GTP/NME1/Tiam1	-0.009	0.11	-9999	-0.54	10	10
PI3K	-0.001	0.007	-9999	-10000	0	0
ARF6	0.012	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0.018	0.015	-9999	-0.3	1	1
TIAM1	-0.03	0.13	-9999	-0.44	43	43
E-cadherin(dimer)/Ca2+	0.03	0.001	-9999	-10000	0	0
AKT1	0	0.004	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
CDH1	0.012	0	-9999	-10000	0	0
RhoA/GDP	0.051	0.022	-9999	-10000	0	0
actin cytoskeleton organization	0.024	0.043	-9999	-0.17	4	4
CDC42/GDP	0.05	0.024	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.021	0.011	-9999	-10000	0	0
ITGB7	-0.006	0.089	-9999	-0.44	19	19
RAC1	0.012	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.032	0.001	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	0.022	0	-9999	-10000	0	0
mol:GDP	0.048	0.024	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0.016	0.013	-9999	-0.25	1	1
JUP	0.011	0.021	-9999	-0.44	1	1
p120 catenin/RhoA/GDP	0.042	0.024	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0.017	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.018	0.015	-9999	-0.3	1	1
RHOA	0.012	0	-9999	-10000	0	0
CDC42	0.011	0.021	-9999	-0.44	1	1
CTNNA1	0.012	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.02	0.035	-9999	-0.24	3	3
NME1	-0.004	0.11	-9999	-0.73	10	10
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.036	0.004	-9999	-10000	0	0
regulation of cell-cell adhesion	-0.001	0.008	-9999	-10000	0	0
WASF2	-0.005	0.015	-9999	-10000	0	0
Rap1/GTP	0	0.007	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.027	0.047	-9999	-10000	0	0
CCND1	0.022	0.042	-9999	-0.3	3	3
VAV2	0.031	0.096	-9999	-0.64	9	9
RAP1/GDP	0.042	0.02	-9999	-10000	0	0
adherens junction assembly	0.035	0.003	-9999	-10000	0	0
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.012	0	-9999	-10000	0	0
PIP5K1C	0.011	0.021	-9999	-0.44	1	1
regulation of heterotypic cell-cell adhesion	0.031	0.045	-9999	-10000	0	0
E-cadherin/beta catenin	0	0.008	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.036	0.004	-9999	-10000	0	0
PIK3CA	0.012	0.001	-9999	-10000	0	0
Rac1/GTP	-0.021	0.068	-9999	-0.36	9	9
E-cadherin/beta catenin/alpha catenin	0.025	0	-9999	-10000	0	0
ITGAE	0.012	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.031	0.004	-9999	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.01	0.03	-9999	-0.44	2	2
SMAD2	0.013	0.01	-9999	-10000	0	0
SMAD3	0.033	0.019	-9999	-10000	0	0
SMAD3/SMAD4	0.039	0.019	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0.024	0.018	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0.034	0.024	-9999	-0.37	1	1
PPM1A	0.012	0	-9999	-10000	0	0
CALM1	0.012	0	-9999	-10000	0	0
SMAD2/SMAD4	0.018	0.018	-9999	-10000	0	0
MAP3K1	0.011	0.021	-9999	-0.44	1	1
TRAP-1/SMAD4	0.017	0.021	-9999	-10000	0	0
MAPK3	0.011	0.021	-9999	-0.44	1	1
MAPK1	0.012	0	-9999	-10000	0	0
NUP214	0.012	0	-9999	-10000	0	0
CTDSP1	0.012	0	-9999	-10000	0	0
CTDSP2	0.012	0	-9999	-10000	0	0
CTDSPL	0.012	0	-9999	-10000	0	0
KPNB1	0.012	0	-9999	-10000	0	0
TGFBRAP1	0.012	0	-9999	-10000	0	0
UBE2I	0.012	0	-9999	-10000	0	0
NUP153	0.012	0.001	-9999	-10000	0	0
KPNA2	0.011	0.035	-9999	-0.73	1	1
PIAS4	0.012	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.015	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.067	0.027	-9999	-10000	0	0
ERC1	0.012	0	-9999	-10000	0	0
RIP2/NOD2	0.004	0.088	-9999	-0.53	12	12
NFKBIA	0.037	0	-9999	-10000	0	0
BIRC2	0.012	0.001	-9999	-10000	0	0
IKBKB	0.012	0	-9999	-10000	0	0
RIPK2	0.012	0	-9999	-10000	0	0
IKBKG	0.032	0.044	-9999	-0.41	2	2
IKK complex/A20	0.046	0.042	-9999	-0.42	1	1
NEMO/A20/RIP2	0.012	0	-9999	-10000	0	0
XPO1	0.012	0	-9999	-10000	0	0
NEMO/ATM	0.037	0.042	-9999	-0.46	1	1
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.017	0	-9999	-10000	0	0
IKK complex/ELKS	-0.005	0.03	-9999	-0.41	1	1
BCL10/MALT1/TRAF6	0.024	0.018	-9999	-10000	0	0
NOD2	-0.007	0.12	-9999	-0.71	12	12
NFKB1	0.015	0	-9999	-10000	0	0
RELA	0.015	0	-9999	-10000	0	0
MALT1	0.011	0.021	-9999	-0.44	1	1
cIAP1/UbcH5C	0.018	0	-9999	-10000	0	0
ATM	0.012	0	-9999	-10000	0	0
TNF/TNFR1A	0.017	0.021	-9999	-0.3	2	2
TRAF6	0.012	0	-9999	-10000	0	0
PRKCA	0.012	0	-9999	-10000	0	0
CHUK	0.012	0	-9999	-10000	0	0
UBE2D3	0.012	0	-9999	-10000	0	0
TNF	0.01	0.03	-9999	-0.44	2	2
NF kappa B1 p50/RelA	0.035	0	-9999	-10000	0	0
BCL10	0.011	0.021	-9999	-0.44	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.037	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.015	0	-9999	-10000	0	0
TNFRSF1A	0.012	0	-9999	-10000	0	0
IKK complex	0.043	0.041	-9999	-0.44	1	1
CYLD	0.011	0.021	-9999	-0.44	1	1
IKK complex/PKC alpha	0.047	0.04	-9999	-0.42	1	1

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.018	0	-9999	-10000	0	0
ATM	0.012	0	-9999	-10000	0	0
UBE2D3	0.012	0	-9999	-10000	0	0
PRKDC	0.012	0	-9999	-10000	0	0
ATR	0.012	0	-9999	-10000	0	0
UBE2L3	0.012	0	-9999	-10000	0	0
FANCD2	0.022	0.014	-9999	-0.28	1	1
protein ubiquitination	0.03	0.035	-9999	-0.4	3	3
XRCC5	0.012	0	-9999	-10000	0	0
XRCC6	0.012	0	-9999	-10000	0	0
M/R/N Complex	0.025	0.013	-9999	-10000	0	0
MRE11A	0.012	0.001	-9999	-10000	0	0
DNA-PK	0.025	0	-9999	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.045	0.007	-9999	-10000	0	0
FANCF	0.012	0	-9999	-10000	0	0
BRCA1	0.012	0	-9999	-10000	0	0
CCNE1	0.007	0.06	-9999	-0.73	3	3
CDK2/Cyclin E1	0.015	0.046	-9999	-0.55	3	3
FANCG	0.012	0	-9999	-10000	0	0
BRCA1/BACH1/BARD1	0.018	0	-9999	-10000	0	0
FANCE	0.012	0	-9999	-10000	0	0
FANCC	0.012	0	-9999	-10000	0	0
NBN	0.011	0.021	-9999	-0.44	1	1
FANCA	0.012	0	-9999	-10000	0	0
DNA repair	0.061	0.01	-9999	-10000	0	0
BRCA1/BARD1/ubiquitin	0.018	0	-9999	-10000	0	0
BARD1/DNA-PK	0.032	0	-9999	-10000	0	0
FANCL	0.012	0	-9999	-10000	0	0
mRNA polyadenylation	-0.018	0	-9999	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0.033	0.017	-9999	-0.31	1	1
BRCA1/BACH1/BARD1/TopBP1	0.025	0	-9999	-10000	0	0
BRCA1/BARD1/P53	0.032	0	-9999	-10000	0	0
BARD1/CSTF1/BRCA1	0.025	0	-9999	-10000	0	0
BRCA1/BACH1	0.012	0	-9999	-10000	0	0
BARD1	0.012	0	-9999	-10000	0	0
PCNA	0.012	0	-9999	-10000	0	0
BRCA1/BARD1/UbcH5C	0.025	0	-9999	-10000	0	0
BRCA1/BARD1/UbcH7	0.025	0	-9999	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	0.032	0	-9999	-10000	0	0
BARD1/DNA-PK/P53	0.037	0	-9999	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.018	0	-9999	-10000	0	0
BRCA1/BARD1/CTIP	0.029	0.016	-9999	-10000	0	0
FA complex	0.035	0	-9999	-10000	0	0
BARD1/EWS	0.018	0	-9999	-10000	0	0
RBBP8	0.018	0.021	-9999	-0.3	2	2
TP53	0.012	0	-9999	-10000	0	0
TOPBP1	0.012	0	-9999	-10000	0	0
G1/S transition of mitotic cell cycle	-0.031	0	-9999	-10000	0	0
BRCA1/BARD1	0.034	0.035	-9999	-0.4	3	3
CSTF1	0.012	0	-9999	-10000	0	0
BARD1/EWS-Fli1	0.009	0	-9999	-10000	0	0
CDK2	0.012	0	-9999	-10000	0	0
UniProt:Q9BZD1	0	0	-9999	-10000	0	0
RAD51	0.012	0	-9999	-10000	0	0
RAD50	0.012	0	-9999	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.018	0	-9999	-10000	0	0
EWSR1	0.012	0	-9999	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.043	0.01	-10000	0	-10000	0	0
CLOCK	0.015	0.002	-10000	0	-10000	0	0
TIMELESS/CRY2	0.038	0.011	-10000	0	-10000	0	0
DEC1/BMAL1	0.006	0.069	-10000	0	-0.55	7	7
ATR	0.012	0	-10000	0	-10000	0	0
NR1D1	0.035	0.026	-10000	0	-0.52	1	1
ARNTL	0.015	0.002	-10000	0	-10000	0	0
TIMELESS	0.036	0.012	-10000	0	-10000	0	0
NPAS2	0.015	0.002	-10000	0	-10000	0	0
CRY2	0.012	0	-10000	0	-10000	0	0
mol:CO	-0.012	0.005	0.095	1	-10000	0	1
CHEK1	0.012	0	-10000	0	-10000	0	0
mol:HEME	0.012	0.005	-10000	0	-0.095	1	1
PER1	0.011	0.021	-10000	0	-0.44	1	1
BMAL/CLOCK/NPAS2	0.039	0.005	-10000	0	-10000	0	0
BMAL1/CLOCK	0.041	0.034	-10000	0	-10000	0	0
S phase of mitotic cell cycle	0.043	0.01	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.043	0.01	-10000	0	-10000	0	0
mol:NADPH	0.012	0.005	-10000	0	-0.095	1	1
PER1/TIMELESS	0.037	0.015	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	-0.007	0.09	-10000	0	-0.73	7	7

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.012	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.022	0.016	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0	0.005	-9999	-10000	0	0
AURKB	0.012	0	-9999	-10000	0	0
AURKC	0.01	0.03	-9999	-0.44	2	2

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.02	0.063	-10000	0	-10000	0	0
CaM/Ca2+	0.009	0	-10000	0	-10000	0	0
AKT1	0.012	0	-10000	0	-10000	0	0
AKT2	0.012	0	-10000	0	-10000	0	0
STXBP4	0.011	0.021	-10000	0	-0.44	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.018	0.072	0.27	5	-10000	0	5
YWHAZ	0.012	0	-10000	0	-10000	0	0
CALM1	0.012	0	-10000	0	-10000	0	0
YWHAQ	0.012	0	-10000	0	-10000	0	0
TBC1D4	0.019	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.012	0	-10000	0	-10000	0	0
YWHAB	0.012	0	-10000	0	-10000	0	0
SNARE/Synip	0.025	0.013	-10000	0	-10000	0	0
YWHAG	0.012	0	-10000	0	-10000	0	0
ASIP	-0.001	0.077	-10000	0	-0.73	5	5
PRKCI	0.01	0.03	-10000	0	-0.44	2	2
AS160/CaM/Ca2+	0.009	0	-10000	0	-10000	0	0
RHOQ	0.012	0	-10000	0	-10000	0	0
GYS1	0.026	0	-10000	0	-10000	0	0
PRKCZ	0.012	0	-10000	0	-10000	0	0
TRIP10	0.012	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.017	0	-10000	0	-10000	0	0
AS160/14-3-3	0.039	0.013	-10000	0	-10000	0	0
VAMP2	0.012	0	-10000	0	-10000	0	0
SLC2A4	0.017	0.076	0.28	5	-10000	0	5
STX4	0.012	0	-10000	0	-10000	0	0
GSK3B	0.022	0	-10000	0	-10000	0	0
SFN	0.01	0.03	-10000	0	-0.44	2	2
LNPEP	0.012	0.001	-10000	0	-10000	0	0
YWHAE	0.012	0	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.012	0	-10000	0	-10000	0	0
mol:PIP3	0.001	0.016	0.24	2	-10000	0	2
FRAP1	0.013	0.007	-10000	0	-10000	0	0
AKT1	0.023	0.015	0.21	2	-10000	0	2
INSR	0.012	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.008	0	-10000	0	-10000	0	0
mol:GTP	0.03	0.008	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.013	-10000	0	-0.26	1	1
TSC2	0.012	0	-10000	0	-10000	0	0
RHEB/GDP	0	0.005	-10000	0	-10000	0	0
TSC1	0.012	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.015	0.001	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.016	-10000	0	-0.31	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.012	0	-10000	0	-10000	0	0
RPS6KB1	0.023	0.019	-10000	0	-0.3	1	1
MAP3K5	0.009	0	-10000	0	-10000	0	0
PIK3R1	0.012	0	-10000	0	-10000	0	0
apoptosis	0.009	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-10000	0	0
EIF4B	0.027	0.017	-10000	0	-0.26	1	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.03	0.021	-10000	0	-0.3	1	1
eIF4E/eIF4G1/eIF4A1	-0.001	0.008	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.023	0.001	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.026	0.01	0.15	2	-10000	0	2
FKBP1A	0.012	0	-10000	0	-10000	0	0
RHEB/GTP	0	0.005	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-10000	0	0
FKBP12/Rapamycin	0.01	0.001	-10000	0	-10000	0	0
PDPK1	0.001	0.014	0.21	2	-10000	0	2
EIF4E	0.01	0.03	-10000	0	-0.44	2	2
ASK1/PP5C	0.021	0.005	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.013	0.028	-10000	0	-0.42	2	2
TSC1/TSC2	0.034	0.009	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RPS6	0.011	0.035	-10000	0	-0.73	1	1
PPP5C	0.012	0	-10000	0	-10000	0	0
EIF4G1	0.012	0	-10000	0	-10000	0	0
IRS1	0.007	0.001	-10000	0	-10000	0	0
INS	0	0	-10000	0	-10000	0	0
PTEN	0.01	0.029	-10000	0	-0.43	2	2
PDK2	0	0.019	0.21	2	-10000	0	2
EIF4EBP1	0.011	0.018	-10000	0	-10000	0	0
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
PPP2R5D	0.018	0.007	-10000	0	-10000	0	0
peptide biosynthetic process	0.014	0.021	-10000	0	-0.44	1	1
RHEB	0.012	0	-10000	0	-10000	0	0
EIF4A1	0.012	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.003	2	-10000	0	2
EEF2	0.014	0.021	-10000	0	-0.44	1	1
eIF4E/4E-BP1	0.016	0.023	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.019	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0.029	0.011	-9999	-10000	0	0
CDKN1B	0.031	0.006	-9999	-10000	0	0
CDKN1A	0.03	0.015	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.012	0	-9999	-10000	0	0
FOXO3	0.031	0.006	-9999	-10000	0	0
AKT1	0.026	0.006	-9999	-10000	0	0
BAD	0.011	0.021	-9999	-0.44	1	1
AKT3	0.01	0.037	-9999	-0.29	7	7
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.031	0.006	-9999	-10000	0	0
AKT1/ASK1	0.03	0.006	-9999	-10000	0	0
BAD/YWHAZ	0.025	0.013	-9999	-10000	0	0
RICTOR	0.008	0.042	-9999	-0.44	4	4
RAF1	0.012	0	-9999	-10000	0	0
JNK cascade	-0.029	0.005	-9999	-10000	0	0
TSC1	0.031	0.006	-9999	-10000	0	0
YWHAZ	0.012	0	-9999	-10000	0	0
AKT1/RAF1	0.032	0.006	-9999	-10000	0	0
EP300	0.012	0	-9999	-10000	0	0
mol:GDP	0.026	0.006	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.031	0.006	-9999	-10000	0	0
YWHAQ	0.012	0	-9999	-10000	0	0
TBC1D4	0.02	0	-9999	-10000	0	0
MAP3K5	0.012	0	-9999	-10000	0	0
MAPKAP1	0.012	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.037	0.009	-9999	-10000	0	0
YWHAH	0.012	0	-9999	-10000	0	0
AKT1S1	0.031	0.006	-9999	-10000	0	0
CASP9	0.031	0.006	-9999	-10000	0	0
YWHAB	0.012	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.037	0.006	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0.025	0	-9999	-10000	0	0
YWHAE	0.012	0	-9999	-10000	0	0
SRC	0.012	0	-9999	-10000	0	0
AKT2/p21CIP1	0.034	0.014	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.016	0.003	-9999	-10000	0	0
CHUK	0.031	0.006	-9999	-10000	0	0
BAD/BCL-XL	0.042	0.011	-9999	-10000	0	0
mTORC2	0.014	0.023	-9999	-0.23	4	4
AKT2	0.015	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.05	0.012	-9999	-10000	0	0
PDPK1	0.012	0	-9999	-10000	0	0
MDM2	0.03	0.012	-9999	-10000	0	0
MAPKKK cascade	-0.031	0.006	-9999	-10000	0	0
MDM2/Cbp/p300	0.042	0.011	-9999	-10000	0	0
TSC1/TSC2	0.035	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.04	0.011	-9999	-10000	0	0
glucose import	-0.003	0.075	-9999	-10000	0	0
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.026	0.006	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	-0.003	0.076	-9999	-10000	0	0
GSK3A	0.031	0.006	-9999	-10000	0	0
FOXO1	0.03	0.012	-9999	-10000	0	0
GSK3B	0.031	0.006	-9999	-10000	0	0
SFN	0.01	0.03	-9999	-0.44	2	2
G1/S transition of mitotic cell cycle	0.036	0.006	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.041	0.012	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
KPNA1	0.012	0	-9999	-10000	0	0
HSP90AA1	0.012	0	-9999	-10000	0	0
YWHAG	0.012	0	-9999	-10000	0	0
RHEB	0.012	0	-9999	-10000	0	0
CREBBP	0.012	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.001	0.017	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.04	0.019	-9999	-10000	0	0
SUMO1	0.01	0.03	-9999	-0.44	2	2
ZFPM1	-0.002	0.1	-9999	-0.73	9	9
NPC/RanGAP1/SUMO1/Ubc9	0.018	0.013	-9999	-10000	0	0
FKBP3	0.011	0.021	-9999	-0.44	1	1
Histones	0.041	0.01	-9999	-10000	0	0
YY1/LSF	0.018	0.045	-9999	-10000	0	0
SMG5	0.012	0	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.029	0.015	-9999	-10000	0	0
I kappa B alpha/HDAC1	0.028	0.011	-9999	-10000	0	0
SAP18	0.012	0	-9999	-10000	0	0
RELA	0.032	0.015	-9999	-10000	0	0
HDAC1/Smad7	0.025	0.013	-9999	-10000	0	0
RANGAP1	0.012	0	-9999	-10000	0	0
HDAC3/TR2	0.028	0.011	-9999	-10000	0	0
NuRD/MBD3 Complex	0.04	0.008	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.035	0.014	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.002	0.069	-9999	-0.44	11	11
GATA1	0.008	0.006	-9999	-10000	0	0
Mad/Max	0.017	0.021	-9999	-0.3	2	2
NuRD/MBD3 Complex/GATA1/Fog1	0.045	0.027	-9999	-10000	0	0
RBBP7	0.012	0	-9999	-10000	0	0
NPC	0.007	0	-9999	-10000	0	0
RBBP4	0.012	0	-9999	-10000	0	0
MAX	0.012	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.012	0	-9999	-10000	0	0
NFKBIA	0.024	0.012	-9999	-10000	0	0
KAT2B	-0.005	0.087	-9999	-0.44	18	18
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.037	0	-9999	-10000	0	0
SIN3 complex	0.032	0	-9999	-10000	0	0
SMURF1	0.012	0	-9999	-10000	0	0
CHD3	0.012	0	-9999	-10000	0	0
SAP30	0.012	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.012	0	-9999	-10000	0	0
YY1/HDAC3	0.03	0.039	-9999	-10000	0	0
YY1/HDAC2	0.019	0.044	-9999	-10000	0	0
YY1/HDAC1	0.019	0.044	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.041	0	-9999	-10000	0	0
PPARG	0.03	0.031	-9999	-10000	0	0
HDAC8/hEST1B	0.025	0	-9999	-10000	0	0
UBE2I	0.012	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.012	0	-9999	-10000	0	0
TNFRSF1A	0.012	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.028	0.016	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.024	0.013	-9999	-10000	0	0
CREBBP	0.012	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.043	0.009	-9999	-10000	0	0
HDAC1	0.012	0	-9999	-10000	0	0
HDAC3	0.024	0.012	-9999	-10000	0	0
HDAC2	0.012	0	-9999	-10000	0	0
YY1	0.015	0.052	-9999	-10000	0	0
HDAC8	0.012	0	-9999	-10000	0	0
SMAD7	0.011	0.021	-9999	-0.44	1	1
NCOR2	0.011	0.021	-9999	-0.44	1	1
MXD1	0.01	0.03	-9999	-0.44	2	2
STAT3	0.022	0	-9999	-10000	0	0
NFKB1	0.012	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.012	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.025	0.042	-9999	-10000	0	0
YY1/SAP30/HDAC1	0.025	0.04	-9999	-10000	0	0
EP300	0.012	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.022	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.012	-9999	-10000	0	0
histone deacetylation	0.041	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.035	0.01	-9999	-10000	0	0
nuclear export	-0.025	0	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
GATAD2B	0.012	0	-9999	-10000	0	0
GATAD2A	0.012	0	-9999	-10000	0	0
GATA2/HDAC3	0.022	0.038	-9999	-10000	0	0
GATA1/HDAC1	0.015	0.004	-9999	-10000	0	0
GATA1/HDAC3	0.025	0.012	-9999	-10000	0	0
CHD4	0.012	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	0.017	0.021	-9999	-0.3	2	2
SIN3/HDAC complex/Mad/Max	0.04	0.012	-9999	-10000	0	0
NuRD Complex	0.047	0.009	-9999	-10000	0	0
positive regulation of chromatin silencing	0.039	0.01	-9999	-10000	0	0
SIN3B	0.012	0	-9999	-10000	0	0
MTA2	0.012	0	-9999	-10000	0	0
SIN3A	0.012	0	-9999	-10000	0	0
XPO1	0.012	0	-9999	-10000	0	0
SUMO1/HDAC1	0.026	0.021	-9999	-0.28	2	2
HDAC complex	0.032	0	-9999	-10000	0	0
GATA1/Fog1	0.004	0.079	-9999	-0.56	9	9
FKBP25/HDAC1/HDAC2	0.025	0.013	-9999	-10000	0	0
TNF	0.01	0.03	-9999	-0.44	2	2
negative regulation of cell growth	0.04	0.012	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.041	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.029	0.012	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.035	0.02	-9999	-10000	0	0
SIN3/HDAC complex/NCoR1	0.039	0	-9999	-10000	0	0
TFCP2	0.011	0.021	-9999	-0.44	1	1
NR2C1	0.012	0	-9999	-10000	0	0
MBD3	0.011	0.021	-9999	-0.44	1	1
MBD2	0.012	0	-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	0.018	0	-9999	-10000	0	0
FBXW11	0.012	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.023	0.001	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.038	0.025	-9999	-10000	0	0
NFKBIA	0.021	0.028	-9999	-10000	0	0
MAPK14	0.012	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.024	0	-9999	-10000	0	0
ARRB2	0.015	0	-9999	-10000	0	0
REL	0.012	0.001	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.024	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.024	0	-9999	-10000	0	0
PIK3CA	0.012	0.001	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.018	0	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
NFKB1	0.019	0	-9999	-10000	0	0
RELA	0.012	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.027	0.028	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.041	0.025	-9999	-10000	0	0
SRC	0.012	0	-9999	-10000	0	0
PI3K	0.018	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.027	0.028	-9999	-10000	0	0
IKBKB	0.012	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.012	0	-9999	-10000	0	0
SYK	0.012	0	-9999	-10000	0	0
I kappa B alpha/PIK3R1	0.027	0.027	-9999	-10000	0	0
cell death	0.039	0.024	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.023	0.001	-9999	-10000	0	0
LCK	-0.001	0.096	-9999	-0.66	9	9
BCL3	0.012	0	-9999	-10000	0	0

×

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	0.012	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.002	-9999	-10000	0	0
MDM2/SUMO1	0.026	0.028	-9999	-0.39	2	2
HDAC4	0.012	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0.002	-9999	-10000	0	0
SUMO1	0.01	0.03	-9999	-0.44	2	2
NPC/RanGAP1/SUMO1	0.014	0.013	-9999	-0.19	2	2
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.023	0.013	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.012	0	-9999	-10000	0	0
SUMO1/HDAC4	0.026	0.021	-9999	-0.28	2	2
SUMO1/HDAC1	0.026	0.021	-9999	-0.28	2	2
RANGAP1	0.012	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.03	0.025	-9999	-0.45	1	1
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.018	0.013	-9999	-10000	0	0
Ran/GTP	0.023	0.012	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.011	0.021	-9999	-0.44	1	1
UBE2I	0.012	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.028	0.012	-9999	-10000	0	0
NPC	0.007	0	-9999	-10000	0	0
PIAS2	0.012	0.001	-9999	-10000	0	0
PIAS1	0.012	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.025	0.013	-9999	-10000	0	0
E-cadherin/beta catenin	0.018	0	-9999	-10000	0	0
CTNNB1	0.012	0	-9999	-10000	0	0
JUP	0.011	0.021	-9999	-0.44	1	1
CDH1	0.012	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	-0.001	0.022	-9999	-0.34	2	2
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.018	0	-9999	-10000	0	0
AP2	0.018	0.015	-9999	-0.3	1	1
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0.017	0	-9999	-10000	0	0
CLTB	0.012	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.022	0	-9999	-10000	0	0
CD4	-0.004	0.085	-9999	-0.44	17	17
CLTA	0.012	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.008	0.03	-9999	-0.43	2	2
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	0.021	0.023	-9999	-0.32	2	2
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.012	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0.006	0.023	-9999	-0.33	2	2
AP2M1	0.012	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.015	0	-9999	-10000	0	0
Rac/GTP	0.01	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.021	0.023	-9999	-0.42	1	1
ARFIP2	0.011	0	-9999	-10000	0	0
COPA	0.012	0	-9999	-10000	0	0
RAC1	0.012	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.022	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0.009	0	-9999	-10000	0	0
GGA3	0.012	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0.017	0	-9999	-10000	0	0
AP2A1	0.011	0.021	-9999	-0.44	1	1
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.022	0.014	-9999	-0.21	1	1
ARF1/GDP/Membrin	0.017	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0.016	0	-9999	-10000	0	0
CYTH2	0.012	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0.017	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.009	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	0.022	0.04	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.008	0.03	-9999	-0.43	2	2
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.019	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	0.008	0.03	-9999	-0.43	2	2
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	0.018	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.014	0.053	-9999	-10000	0	0

×

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	0.018	-9999	-9999
FBXW11	0.012	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.012	-9999	-9999
CHUK	0.012	-9999	-9999
NF kappa B2 p100/RelB	0.037	-9999	-9999
NFKB1	0.012	-9999	-9999
MAP3K14	0.012	-9999	-9999
NF kappa B1 p50/RelB	0.018	-9999	-9999
RELB	0.012	-9999	-9999
NFKB2	0.012	-9999	-9999
NF kappa B2 p52/RelB	0.017	-9999	-9999
regulation of B cell activation	0.017	-9999	-9999

pid_entity	TCGA.WS.AB45	TCGA.T9.A92H	TCGA.SS.A7HO	TCGA.RU.A8FL
109_MAP3K5	0.046	0.046	-0.19	-0.19
47_PPARGC1A	0.012	0.012	0.012	0.012
105_BMP4	0.012	0.012	0.012	0.012
105_BMP6	0.012	0.012	-0.44	0.012
105_BMP7	-0.44	0.012	0.012	-0.73
105_BMP2	0.012	0.012	-0.44	-0.44
131_RELN/VLDLR	-0.43	-0.43	-0.43	-0.64
30_TGFB1/TGF beta receptor Type II	0.012	0.012	0.017	0.017
84_STAT5B	-0.035	0.04	-0.037	-0.023
84_STAT5A	-0.035	0.04	-0.037	-0.023