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

Pathway.Name	Avg.Num.Perturbations
Ephrin A reverse signaling	95
IL23-mediated signaling events	95
Signaling mediated by p38-alpha and p38-beta	91
Wnt signaling	87
IL4-mediated signaling events	86
Noncanonical Wnt signaling pathway	66
amb2 Integrin signaling	64
Syndecan-4-mediated signaling events	63
Glypican 1 network	62
TCR signaling in naïve CD8+ T cells	58

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
Ephrin A reverse signaling	0.1597	95	669	7	-0.097	0	1000	-1000	-0.016	-1000
IL23-mediated signaling events	0.1597	95	5711	60	-0.54	0.011	1000	-1000	-0.18	-1000
Signaling mediated by p38-alpha and p38-beta	0.1529	91	4040	44	-0.18	0.011	1000	-1000	-0.039	-1000
Wnt signaling	0.1462	87	613	7	-0.14	0.004	1000	-1000	-0.025	-1000
IL4-mediated signaling events	0.1445	86	7835	91	-0.68	0.61	1000	-1000	-0.17	-1000
Noncanonical Wnt signaling pathway	0.1109	66	1733	26	-0.14	0.011	1000	-1000	-0.045	-1000
amb2 Integrin signaling	0.1076	64	5258	82	-0.16	0.015	1000	-1000	-0.073	-1000
Syndecan-4-mediated signaling events	0.1059	63	4285	67	-0.18	0.038	1000	-1000	-0.083	-1000
Glypican 1 network	0.1042	62	2976	48	-0.2	0.014	1000	-1000	-0.039	-1000
TCR signaling in naïve CD8+ T cells	0.0975	58	5452	93	-0.12	0.055	1000	-1000	-0.075	-1000
EGFR-dependent Endothelin signaling events	0.0975	58	1234	21	-0.18	0.016	1000	-1000	-0.061	-1000
IL12-mediated signaling events	0.0958	57	5007	87	-0.29	0.066	1000	-1000	-0.14	-1000
Syndecan-1-mediated signaling events	0.0941	56	1919	34	-0.14	0.011	1000	-1000	-0.045	-1000
FOXA2 and FOXA3 transcription factor networks	0.0941	56	2601	46	-0.43	0.016	1000	-1000	-0.12	-1000
Signaling events mediated by the Hedgehog family	0.0924	55	2892	52	-0.13	0.08	1000	-1000	-0.045	-1000
TCGA08_retinoblastoma	0.0891	53	428	8	-0.07	0.027	1000	-1000	-0.014	-1000
BCR signaling pathway	0.0891	53	5296	99	-0.17	0.014	1000	-1000	-0.08	-1000
Endothelins	0.0857	51	4974	96	-0.16	0.011	1000	-1000	-0.08	-1000
Ephrin B reverse signaling	0.0840	50	2404	48	-0.15	0.044	1000	-1000	-0.063	-1000
BMP receptor signaling	0.0824	49	3981	81	-0.17	0.026	1000	-1000	-0.075	-1000
Reelin signaling pathway	0.0824	49	2783	56	-0.12	0.021	1000	-1000	-0.071	-1000
HIF-1-alpha transcription factor network	0.0807	48	3660	76	-0.31	0.016	1000	-1000	-0.19	-1000
p75(NTR)-mediated signaling	0.0807	48	6026	125	-0.18	0.031	1000	-1000	-0.085	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0790	47	3245	68	-0.31	0.11	1000	-1000	-0.12	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0773	46	1589	34	-0.059	0.011	1000	-1000	-0.039	-1000
Fc-epsilon receptor I signaling in mast cells	0.0756	45	4447	97	-0.14	0.029	1000	-1000	-0.072	-1000
TCGA08_p53	0.0739	44	310	7	-0.05	0.03	1000	-1000	-0.011	-1000
Calcium signaling in the CD4+ TCR pathway	0.0739	44	1366	31	-0.2	0.011	1000	-1000	-0.067	-1000
Syndecan-2-mediated signaling events	0.0689	41	2830	69	-0.11	0.023	1000	-1000	-0.029	-1000
Thromboxane A2 receptor signaling	0.0672	40	4233	105	-0.18	0.044	1000	-1000	-0.063	-1000
Osteopontin-mediated events	0.0655	39	1495	38	-0.16	0.011	1000	-1000	-0.079	-1000
Glucocorticoid receptor regulatory network	0.0655	39	4496	114	-0.34	0.21	1000	-1000	-0.07	-1000
Signaling events regulated by Ret tyrosine kinase	0.0655	39	3238	82	-0.11	0.011	1000	-1000	-0.076	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0622	37	4484	120	-0.18	0.14	1000	-1000	-0.067	-1000
Visual signal transduction: Cones	0.0605	36	1374	38	-0.053	0.007	1000	-1000	-0.051	-1000
JNK signaling in the CD4+ TCR pathway	0.0571	34	589	17	-0.047	0.011	1000	-1000	-0.034	-1000
Canonical Wnt signaling pathway	0.0571	34	1735	51	-0.18	0.088	1000	-1000	-0.057	-1000
LPA receptor mediated events	0.0571	34	3553	102	-0.11	0.012	1000	-1000	-0.075	-1000
Effects of Botulinum toxin	0.0555	33	874	26	-0.12	0.01	1000	-1000	-0.052	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0555	33	2643	78	-0.084	0.055	1000	-1000	-0.079	-1000
Caspase cascade in apoptosis	0.0538	32	2436	74	-0.085	0.042	1000	-1000	-0.04	-1000
Visual signal transduction: Rods	0.0538	32	1684	52	-0.12	0.011	1000	-1000	-0.062	-1000
Glypican 2 network	0.0521	31	127	4	-0.011	-0.008	1000	-1000	-0.017	-1000
Cellular roles of Anthrax toxin	0.0504	30	1193	39	-0.045	0.011	1000	-1000	-0.021	-1000
Presenilin action in Notch and Wnt signaling	0.0504	30	1865	61	-0.18	0.059	1000	-1000	-0.059	-1000
IL1-mediated signaling events	0.0504	30	1871	62	-0.1	0.02	1000	-1000	-0.087	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0504	30	2703	88	-0.12	0.044	1000	-1000	-0.1	-1000
Arf6 signaling events	0.0487	29	1857	62	-0.18	0.024	1000	-1000	-0.056	-1000
Integrins in angiogenesis	0.0487	29	2476	84	-0.16	0.018	1000	-1000	-0.081	-1000
a4b1 and a4b7 Integrin signaling	0.0471	28	140	5	-0.022	-0.004	1000	-1000	-0.018	-1000
Signaling events mediated by PTP1B	0.0471	28	2151	76	-0.18	0.029	1000	-1000	-0.071	-1000
FAS signaling pathway (CD95)	0.0454	27	1271	47	-0.16	0.014	1000	-1000	-0.045	-1000
Retinoic acid receptors-mediated signaling	0.0437	26	1537	58	-0.15	0.019	1000	-1000	-0.071	-1000
Ras signaling in the CD4+ TCR pathway	0.0437	26	451	17	-0.048	0.011	1000	-1000	-0.042	-1000
EPHB forward signaling	0.0420	25	2126	85	-0.1	0.06	1000	-1000	-0.079	-1000
IL27-mediated signaling events	0.0420	25	1306	51	-0.19	0.024	1000	-1000	-0.077	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0403	24	1338	54	-0.13	0.022	1000	-1000	-0.086	-1000
LPA4-mediated signaling events	0.0387	23	287	12	-0.058	0.015	1000	-1000	-0.027	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0387	23	860	37	-0.12	0.026	1000	-1000	-0.044	-1000
IL6-mediated signaling events	0.0387	23	1757	75	-0.11	0.042	1000	-1000	-0.073	-1000
Plasma membrane estrogen receptor signaling	0.0387	23	2009	86	-0.073	0.017	1000	-1000	-0.076	-1000
Nongenotropic Androgen signaling	0.0370	22	1171	52	-0.051	0.012	1000	-1000	-0.051	-1000
IGF1 pathway	0.0370	22	1291	57	-0.074	0.023	1000	-1000	-0.086	-1000
Coregulation of Androgen receptor activity	0.0353	21	1625	76	-0.16	0.04	1000	-1000	-0.042	-1000
S1P1 pathway	0.0353	21	776	36	-0.1	0.011	1000	-1000	-0.051	-1000
PDGFR-alpha signaling pathway	0.0336	20	890	44	-0.063	0.017	1000	-1000	-0.054	-1000
Class I PI3K signaling events	0.0303	18	1375	73	-0.12	0.024	1000	-1000	-0.061	-1000
IL2 signaling events mediated by STAT5	0.0286	17	389	22	-0.049	0.016	1000	-1000	-0.055	-1000
Regulation of Telomerase	0.0286	17	1745	102	-0.18	0.036	1000	-1000	-0.092	-1000
ErbB4 signaling events	0.0269	16	1120	69	-0.16	0.036	1000	-1000	-0.082	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0269	16	851	52	-0.12	0.034	1000	-1000	-0.044	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0269	16	530	33	-0.077	0.029	1000	-1000	-0.041	-1000
Regulation of nuclear SMAD2/3 signaling	0.0252	15	2104	136	-0.08	0.038	1000	-1000	-0.056	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0252	15	436	28	-0.046	0.018	1000	-1000	-0.037	-1000
Nectin adhesion pathway	0.0252	15	1002	63	-0.032	0.02	1000	-1000	-0.064	-1000
Signaling events mediated by PRL	0.0252	15	529	34	-0.024	0.027	1000	-1000	-0.043	-1000
FOXM1 transcription factor network	0.0252	15	767	51	-0.12	0.075	1000	-1000	-0.2	-1000
ErbB2/ErbB3 signaling events	0.0235	14	956	65	-0.067	0.016	1000	-1000	-0.061	-1000
Ceramide signaling pathway	0.0235	14	1065	76	-0.18	0.058	1000	-1000	-0.046	-1000
Signaling events mediated by HDAC Class III	0.0235	14	581	40	-0.047	0.017	1000	-1000	-0.025	-1000
Syndecan-3-mediated signaling events	0.0235	14	490	35	-0.11	0.031	1000	-1000	-0.041	-1000
Regulation of p38-alpha and p38-beta	0.0235	14	774	54	-0.12	0.027	1000	-1000	-0.055	-1000
PLK2 and PLK4 events	0.0218	13	39	3	-0.003	0.009	1000	-1000	-0.013	-1000
IFN-gamma pathway	0.0218	13	939	68	-0.066	0.02	1000	-1000	-0.089	-1000
PDGFR-beta signaling pathway	0.0218	13	1354	97	-0.098	0.032	1000	-1000	-0.071	-1000
S1P4 pathway	0.0218	13	327	25	-0.046	0.015	1000	-1000	-0.039	-1000
Signaling mediated by p38-gamma and p38-delta	0.0202	12	184	15	-0.024	0.017	1000	-1000	-0.028	-1000
Class IB PI3K non-lipid kinase events	0.0202	12	36	3	-0.001	-1000	1000	-1000	-0.008	-1000
Regulation of Androgen receptor activity	0.0202	12	900	70	-0.2	0.027	1000	-1000	-0.064	-1000
IL2 signaling events mediated by PI3K	0.0185	11	662	58	-0.047	0.027	1000	-1000	-0.078	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0185	11	519	45	-0.063	0.039	1000	-1000	-0.084	-1000
S1P3 pathway	0.0185	11	465	42	-0.046	0.018	1000	-1000	-0.041	-1000
Signaling events mediated by HDAC Class II	0.0168	10	777	75	-0.038	0.026	1000	-1000	-0.038	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0168	10	878	85	-0.037	0.028	1000	-1000	-0.065	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0168	10	885	83	-0.15	0.048	1000	-1000	-0.069	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0168	10	272	27	-0.017	0.016	1000	-1000	-0.046	-1000
Aurora B signaling	0.0168	10	712	67	-0.12	0.028	1000	-1000	-0.055	-1000
BARD1 signaling events	0.0151	9	557	57	-0.044	0.048	1000	-1000	-0.055	-1000
EPO signaling pathway	0.0151	9	495	55	-0.025	0.04	1000	-1000	-0.078	-1000
S1P5 pathway	0.0151	9	160	17	-0.046	0.011	1000	-1000	-0.035	-1000
TCGA08_rtk_signaling	0.0151	9	237	26	-0.044	0.035	1000	-1000	-0.023	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0151	9	682	74	-0.18	0.051	1000	-1000	-0.078	-1000
Insulin Pathway	0.0151	9	668	74	-0.12	0.027	1000	-1000	-0.084	-1000
Rapid glucocorticoid signaling	0.0151	9	188	20	-0.02	0.011	1000	-1000	-0.019	-1000
p38 MAPK signaling pathway	0.0151	9	405	44	-0.054	0.02	1000	-1000	-0.063	-1000
Hedgehog signaling events mediated by Gli proteins	0.0134	8	569	65	-0.046	0.035	1000	-1000	-0.062	-1000
Paxillin-dependent events mediated by a4b1	0.0134	8	308	36	-0.022	0.02	1000	-1000	-0.064	-1000
VEGFR1 specific signals	0.0134	8	474	56	-0.017	0.031	1000	-1000	-0.059	-1000
Canonical NF-kappaB pathway	0.0101	6	238	39	-0.017	0.054	1000	-1000	-0.07	-1000
Aurora A signaling	0.0101	6	389	60	-0.052	0.029	1000	-1000	-0.032	-1000
Aurora C signaling	0.0101	6	42	7	-0.009	0.011	1000	-1000	-0.026	-1000
Signaling events mediated by HDAC Class I	0.0101	6	657	104	-0.022	0.041	1000	-1000	-0.057	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0101	6	838	125	-0.041	0.055	1000	-1000	-0.084	-1000
ceramide signaling pathway	0.0084	5	245	49	-0.016	0.029	1000	-1000	-0.05	-1000
HIF-2-alpha transcription factor network	0.0084	5	220	43	-0.08	0.082	1000	-1000	-0.081	-1000
Atypical NF-kappaB pathway	0.0084	5	161	31	-0.031	0.028	1000	-1000	-0.038	-1000
E-cadherin signaling in the nascent adherens junction	0.0084	5	441	76	-0.044	0.044	1000	-1000	-0.078	-1000
Arf6 downstream pathway	0.0067	4	212	43	-0.042	0.025	1000	-1000	-0.027	-1000
mTOR signaling pathway	0.0067	4	227	53	-0.006	0.025	1000	-1000	-0.059	-1000
TRAIL signaling pathway	0.0067	4	214	48	-0.014	0.037	1000	-1000	-0.061	-1000
FoxO family signaling	0.0067	4	275	64	-0.082	0.098	1000	-1000	-0.075	-1000
Arf6 trafficking events	0.0067	4	349	71	-0.038	0.027	1000	-1000	-0.067	-1000
PLK1 signaling events	0.0050	3	278	85	-0.007	0.029	1000	-1000	-0.04	-1000
Class I PI3K signaling events mediated by Akt	0.0050	3	266	68	-0.032	0.042	1000	-1000	-0.045	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0034	2	57	23	0.004	0.034	1000	-1000	-0.036	-1000
Circadian rhythm pathway	0.0034	2	63	22	-0.011	0.036	1000	-1000	-0.046	-1000
Insulin-mediated glucose transport	0.0034	2	91	32	0	0.033	1000	-1000	-0.047	-1000
E-cadherin signaling in keratinocytes	0.0034	2	100	43	-0.032	0.037	1000	-1000	-0.058	-1000
Arf1 pathway	0.0034	2	119	54	-0.014	0.02	1000	-1000	-0.034	-1000
Alternative NF-kappaB pathway	0.0034	2	32	13	0	0.029	1000	-1000	-0.03	-1000
E-cadherin signaling events	0.0017	1	5	5	0.01	0.022	1000	-1000	-0.025	-1000
Total	NA	3396	195401	7203	-14	-1000	131000	-131000	-7.9	-131000

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.061	0.14	-9999	-0.32	133	133
EFNA5	-0.097	0.22	-9999	-0.52	122	122
FYN	-0.052	0.13	-9999	-0.29	135	135
neuron projection morphogenesis	-0.061	0.14	-9999	-0.32	133	133
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.061	0.14	-9999	-0.32	133	133
EPHA5	-0.004	0.068	-9999	-0.46	13	13

×

IL23-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.43	0.54	-10000	0	-1.2	151	151
IL23A	-0.44	0.55	-10000	0	-1.3	141	141
NF kappa B1 p50/RelA/I kappa B alpha	-0.48	0.5	-10000	0	-1.2	167	167
positive regulation of T cell mediated cytotoxicity	-0.48	0.62	-10000	0	-1.3	159	159
ITGA3	-0.41	0.52	-10000	0	-1.2	138	138
IL17F	-0.29	0.34	-10000	0	-0.75	135	135
IL12B	-0.017	0.078	-10000	0	-0.48	14	14
STAT1 (dimer)	-0.46	0.59	-10000	0	-1.3	158	158
CD4	-0.42	0.52	-10000	0	-1.2	143	143
IL23	-0.43	0.52	-10000	0	-1.2	137	137
IL23R	-0.1	0.3	-10000	0	-1.4	27	27
IL1B	-0.46	0.57	-10000	0	-1.3	140	140
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.54	0.61	-10000	0	-1.3	205	205
TYK2	-0.002	0.033	-10000	0	-0.62	1	1
STAT4	-0.027	0.14	-10000	0	-0.56	40	40
STAT3	0.011	0.002	-10000	0	-10000	0	0
IL18RAP	-0.035	0.15	-10000	0	-0.55	48	48
IL12RB1	-0.046	0.16	-10000	0	-0.57	48	48
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
IL12Rbeta1/TYK2	-0.035	0.12	-10000	0	-0.43	49	49
IL23R/JAK2	-0.12	0.3	-10000	0	-1.3	29	29
positive regulation of chronic inflammatory response	-0.48	0.62	-10000	0	-1.3	159	159
natural killer cell activation	0.008	0.017	0.069	32	-10000	0	32
JAK2	-0.02	0.11	-10000	0	-0.57	21	21
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
NFKB1	0.008	0.025	-10000	0	-0.59	1	1
RELA	0.009	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.4	0.49	-10000	0	-1.1	139	139
ALOX12B	-0.47	0.56	-10000	0	-1.2	171	171
CXCL1	-0.43	0.54	-10000	0	-1.2	131	131
T cell proliferation	-0.48	0.62	-10000	0	-1.3	159	159
NFKBIA	0.009	0.004	-10000	0	-10000	0	0
IL17A	-0.25	0.3	-10000	0	-0.62	138	138
PI3K	-0.48	0.51	-10000	0	-1.2	164	164
IFNG	-0.019	0.05	0.14	18	-0.12	50	68
STAT3 (dimer)	-0.47	0.48	-10000	0	-1.1	171	171
IL18R1	-0.013	0.11	-10000	0	-0.56	25	25
IL23/IL23R/JAK2/TYK2/SOCS3	-0.24	0.32	-10000	0	-0.74	101	101
IL18/IL18R	-0.025	0.14	-10000	0	-0.38	64	64
macrophage activation	-0.023	0.018	-10000	0	-0.045	117	117
TNF	-0.45	0.56	-10000	0	-1.2	150	150
STAT3/STAT4	-0.49	0.52	-10000	0	-1.2	165	165
STAT4 (dimer)	-0.47	0.6	-10000	0	-1.3	162	162
IL18	0.002	0.067	-10000	0	-0.54	9	9
IL19	-0.41	0.51	-10000	0	-1.2	132	132
STAT5A (dimer)	-0.46	0.59	-10000	0	-1.3	158	158
STAT1	0.006	0.051	-10000	0	-0.5	6	6
SOCS3	-0.002	0.082	-10000	0	-0.5	16	16
CXCL9	-0.47	0.58	-10000	0	-1.3	164	164
MPO	-0.44	0.54	-10000	0	-1.2	158	158
positive regulation of humoral immune response	-0.48	0.62	-10000	0	-1.3	159	159
IL23/IL23R/JAK2/TYK2	-0.54	0.75	-10000	0	-1.5	159	159
IL6	-0.48	0.57	-10000	0	-1.2	176	176
STAT5A	0.011	0	-10000	0	-10000	0	0
IL2	0.004	0.029	-10000	0	-0.46	2	2
positive regulation of tyrosine phosphorylation of STAT protein	0.008	0.017	0.069	32	-10000	0	32
CD3E	-0.42	0.53	-10000	0	-1.2	134	134
keratinocyte proliferation	-0.48	0.62	-10000	0	-1.3	159	159
NOS2	-0.48	0.57	-10000	0	-1.2	174	174

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.16	0.35	-9999	-0.94	80	80
MKNK1	0.011	0	-9999	-10000	0	0
MAPK14	-0.063	0.14	-9999	-0.31	103	103
ATF2/c-Jun	-0.045	0.15	-9999	-0.45	35	35
MAPK11	-0.078	0.17	-9999	-0.36	129	129
MITF	-0.094	0.2	-9999	-0.4	144	144
MAPKAPK5	-0.074	0.18	-9999	-0.38	124	124
KRT8	-0.075	0.18	-9999	-0.39	125	125
MAPKAPK3	0.011	0	-9999	-10000	0	0
MAPKAPK2	0.011	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.11	0.23	-9999	-0.5	124	124
CEBPB	-0.075	0.18	-9999	-0.38	126	126
SLC9A1	-0.075	0.18	-9999	-0.39	126	126
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.071	0.18	-9999	-0.39	114	114
p38alpha-beta/MNK1	-0.075	0.19	-9999	-0.4	124	124
JUN	-0.044	0.14	-9999	-0.44	35	35
PPARGC1A	-0.11	0.22	-9999	-0.42	161	161
USF1	-0.074	0.18	-9999	-0.39	112	112
RAB5/GDP/GDI1	-0.073	0.12	-9999	-0.42	35	35
NOS2	-0.18	0.4	-9999	-1.1	86	86
DDIT3	-0.075	0.18	-9999	-0.39	113	113
RAB5A	0.006	0.054	-9999	-0.58	5	5
HSPB1	-0.06	0.16	-9999	-0.46	39	39
p38alpha-beta/HBP1	-0.075	0.19	-9999	-0.4	124	124
CREB1	-0.074	0.18	-9999	-0.41	113	113
RAB5/GDP	0.005	0.04	-9999	-0.43	5	5
EIF4E	-0.064	0.17	-9999	-0.56	32	32
RPS6KA4	-0.074	0.18	-9999	-0.39	113	113
PLA2G4A	-0.15	0.22	-9999	-0.46	140	140
GDI1	-0.074	0.18	-9999	-0.38	124	124
TP53	-0.12	0.24	-9999	-0.51	126	126
RPS6KA5	-0.076	0.18	-9999	-0.38	126	126
ESR1	-0.099	0.2	-9999	-0.42	145	145
HBP1	0.011	0	-9999	-10000	0	0
MEF2C	-0.08	0.18	-9999	-0.4	119	119
MEF2A	-0.075	0.18	-9999	-0.4	112	112
EIF4EBP1	-0.074	0.18	-9999	-0.41	112	112
KRT19	-0.076	0.18	-9999	-0.39	125	125
ELK4	-0.076	0.18	-9999	-0.41	112	112
ATF6	-0.074	0.18	-9999	-0.39	112	112
ATF1	-0.074	0.18	-9999	-0.41	112	112
p38alpha-beta/MAPKAPK2	-0.075	0.19	-9999	-0.4	124	124
p38alpha-beta/MAPKAPK3	-0.075	0.19	-9999	-0.4	124	124

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.13	0.21	-9999	-0.37	196	196
FZD6	0.004	0.064	-9999	-0.58	7	7
WNT6	-0.1	0.21	-9999	-0.5	130	130
WNT4	-0.053	0.18	-9999	-0.54	70	70
FZD3	-0.009	0.11	-9999	-0.58	20	20
WNT5A	-0.008	0.1	-9999	-0.55	21	21
WNT11	-0.14	0.24	-9999	-0.52	169	169

×

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	-0.53	0.57	-10000	0	-1.3	175	175
STAT6 (cleaved dimer)	-0.58	0.56	-10000	0	-1.2	213	213
IGHG1	-0.16	0.18	-10000	0	-0.56	4	4
IGHG3	-0.51	0.54	-10000	0	-1.2	204	204
AKT1	-0.24	0.29	-10000	0	-0.78	62	62
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.19	0.26	-10000	0	-0.85	35	35
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.24	0.28	-10000	0	-0.8	45	45
THY1	-0.53	0.57	-10000	0	-1.3	173	173
MYB	0.002	0.072	-10000	0	-0.58	9	9
HMGA1	0.006	0.055	-10000	0	-0.54	6	6
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.32	0.35	-10000	0	-0.83	116	116
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.25	0.29	-10000	0	-0.8	49	49
SP1	0.015	0.025	-10000	0	-0.58	1	1
INPP5D	-0.017	0.12	-10000	0	-0.58	28	28
SOCS5	0.026	0.016	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.54	0.59	-10000	0	-1.3	185	185
SOCS1	-0.35	0.36	-10000	0	-0.81	151	151
SOCS3	-0.26	0.31	-10000	0	-0.84	73	73
FCER2	-0.52	0.56	-10000	0	-1.3	171	171
PARP14	0.008	0.021	-10000	0	-0.46	1	1
CCL17	-0.57	0.61	-10000	0	-1.3	189	189
GRB2	0.011	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.2	0.23	-10000	0	-0.75	29	29
T cell proliferation	-0.54	0.59	-10000	0	-1.3	181	181
IL4R/JAK1	-0.54	0.57	-10000	0	-1.3	176	176
EGR2	-0.57	0.61	-10000	0	-1.4	182	182
JAK2	-0.033	0.11	-10000	0	-0.58	21	21
JAK3	0.002	0.077	-10000	0	-0.53	12	12
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
JAK1	0.003	0.043	-10000	0	-0.58	3	3
COL1A2	-0.2	0.34	-10000	0	-1.2	43	43
CCL26	-0.58	0.62	-10000	0	-1.3	198	198
IL4R	-0.57	0.61	-10000	0	-1.4	175	175
PTPN6	0.023	0.012	-10000	0	-10000	0	0
IL13RA2	-0.59	0.63	-10000	0	-1.4	189	189
IL13RA1	-0.017	0.057	-10000	0	-0.59	4	4
IRF4	-0.27	0.49	-10000	0	-1.4	86	86
ARG1	-0.14	0.18	-10000	0	-0.77	18	18
CBL	-0.3	0.33	-10000	0	-0.82	94	94
GTF3A	0.011	0.04	-10000	0	-0.51	3	3
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
IL13RA1/JAK2	-0.032	0.097	-10000	0	-0.45	23	23
IRF4/BCL6	-0.24	0.45	-10000	0	-1.3	81	81
CD40LG	-0.036	0.16	-10000	0	-0.58	47	47
MAPK14	-0.3	0.34	-10000	0	-0.87	84	84
mitosis	-0.23	0.28	-10000	0	-0.73	62	62
STAT6	-0.64	0.75	-10000	0	-1.5	187	187
SPI1	-0.013	0.12	-10000	0	-0.52	28	28
RPS6KB1	-0.22	0.27	-10000	0	-0.71	61	61
STAT6 (dimer)	-0.65	0.77	-10000	0	-1.6	187	187
STAT6 (dimer)/PARP14	-0.59	0.64	-10000	0	-1.4	181	181
mast cell activation	0.012	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.25	0.3	-10000	0	-0.82	63	63
FRAP1	-0.24	0.29	-10000	0	-0.78	62	62
LTA	-0.56	0.6	-10000	0	-1.3	181	181
FES	0.001	0.077	-10000	0	-0.56	11	11
T-helper 1 cell differentiation	0.61	0.67	1.4	188	-10000	0	188
CCL11	-0.57	0.62	-10000	0	-1.4	185	185
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.24	0.3	-10000	0	-0.82	58	58
IL2RG	0	0.083	-10000	0	-0.55	13	13
IL10	-0.57	0.62	-10000	0	-1.3	186	186
IRS1	0.002	0.072	-10000	0	-0.58	9	9
IRS2	0.003	0.068	-10000	0	-0.54	9	9
IL4	-0.11	0.12	-10000	0	-10000	0	0
IL5	-0.53	0.57	-10000	0	-1.3	176	176
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.41	0.42	-10000	0	-0.92	184	184
COL1A1	-0.25	0.4	-10000	0	-1.2	64	64
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.55	0.59	-10000	0	-1.4	160	160
IL2R gamma/JAK3	-0.002	0.083	-10000	0	-0.39	25	25
TFF3	-0.57	0.61	-10000	0	-1.4	176	176
ALOX15	-0.62	0.64	-10000	0	-1.4	200	200
MYBL1	0	0.079	-10000	0	-0.55	12	12
T-helper 2 cell differentiation	-0.43	0.45	-10000	0	-0.98	180	180
SHC1	0.011	0	-10000	0	-10000	0	0
CEBPB	0.009	0.043	-10000	0	-0.49	4	4
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.24	0.28	-10000	0	-0.84	38	38
mol:PI-3-4-5-P3	-0.24	0.29	-10000	0	-0.78	62	62
PI3K	-0.26	0.31	-10000	0	-0.85	61	61
DOK2	-0.01	0.11	-10000	0	-0.55	23	23
ETS1	0.016	0.059	-10000	0	-0.45	9	9
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.18	0.22	-10000	0	-0.71	27	27
ITGB3	-0.53	0.58	-10000	0	-1.3	172	172
PIGR	-0.68	0.7	-10000	0	-1.5	231	231
IGHE	0.04	0.052	0.27	9	-0.31	1	10
MAPKKK cascade	-0.18	0.22	-10000	0	-0.7	27	27
BCL6	0.01	0.038	-10000	0	-0.45	4	4
OPRM1	-0.53	0.57	-10000	0	-1.3	175	175
RETNLB	-0.68	0.67	-10000	0	-1.4	238	238
SELP	-0.6	0.66	-10000	0	-1.4	187	187
AICDA	-0.52	0.55	-10000	0	-1.2	175	175

×

Noncanonical Wnt signaling pathway

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
NFATC2	-0.037	0.16	-9999	-0.57	50	50
GNB1/GNG2	-0.11	0.19	-9999	-0.49	81	81
mol:DAG	-0.094	0.18	-9999	-0.44	81	81
PLCG1	-0.097	0.18	-9999	-0.46	81	81
YES1	-0.12	0.2	-9999	-0.51	83	83
FZD3	-0.009	0.11	-9999	-0.58	20	20
FZD6	0.004	0.064	-9999	-0.58	7	7
G protein	-0.098	0.18	-9999	-0.46	81	81
MAP3K7	-0.083	0.16	-9999	-0.41	73	73
mol:Ca2+	-0.091	0.17	-9999	-0.43	81	81
mol:IP3	-0.094	0.18	-9999	-0.44	81	81
NLK	-0.005	0.009	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
CAMK2A	-0.095	0.17	-9999	-0.42	92	92
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.13	0.21	-9999	-0.37	196	196
CSNK1A1	0.009	0.034	-9999	-0.58	2	2
GNAS	-0.12	0.2	-9999	-0.51	79	79
GO:0007205	-0.092	0.17	-9999	-0.44	80	80
WNT6	-0.1	0.21	-9999	-0.5	130	130
WNT4	-0.053	0.18	-9999	-0.54	70	70
NFAT1/CK1 alpha	-0.12	0.22	-9999	-0.55	85	85
GNG2	0.004	0.063	-9999	-0.53	8	8
WNT5A	-0.008	0.1	-9999	-0.55	21	21
WNT11	-0.14	0.24	-9999	-0.52	169	169
CDC42	-0.11	0.2	-9999	-0.5	82	82

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.083	0.22	-9999	-0.53	93	93
alphaM/beta2 Integrin/GPIbA	-0.073	0.19	-9999	-0.48	92	92
alphaM/beta2 Integrin/proMMP-9	-0.098	0.24	-9999	-0.54	106	106
PLAUR	0.01	0.031	-9999	-0.52	2	2
HMGB1	-0.012	0.097	-9999	-0.59	16	16
alphaM/beta2 Integrin/Talin	-0.058	0.18	-9999	-0.48	75	75
AGER	-0.011	0.094	-9999	-0.58	15	15
RAP1A	0.01	0.024	-9999	-0.58	1	1
SELPLG	-0.007	0.099	-9999	-0.55	19	19
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.088	0.21	-9999	-0.47	103	103
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.059	0.18	-9999	-0.52	79	79
CYR61	-0.023	0.13	-9999	-0.48	42	42
TLN1	0.01	0.024	-9999	-0.58	1	1
Rap1/GTP	-0.12	0.17	-9999	-0.45	88	88
RHOA	0.01	0.024	-9999	-0.58	1	1
P-selectin oligomer	-0.082	0.21	-9999	-0.55	99	99
MYH2	-0.13	0.2	-9999	-0.46	114	114
MST1R	0.006	0.054	-9999	-0.58	5	5
leukocyte activation during inflammatory response	-0.14	0.19	-9999	-0.43	125	125
APOB	-0.12	0.22	-9999	-0.5	145	145
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.034	0.15	-9999	-0.53	50	50
JAM3	0.007	0.047	-9999	-0.46	6	6
GP1BA	-0.015	0.11	-9999	-0.52	28	28
alphaM/beta2 Integrin/CTGF	-0.067	0.19	-9999	-0.5	78	78
alphaM/beta2 Integrin	-0.14	0.21	-9999	-0.46	125	125
JAM3 homodimer	0.007	0.047	-9999	-0.46	6	6
ICAM2	0.002	0.07	-9999	-0.5	11	11
ICAM1	0.006	0.053	-9999	-0.52	6	6
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.13	0.2	-9999	-0.45	125	125
cell adhesion	-0.073	0.19	-9999	-0.47	92	92
NFKB1	-0.11	0.24	-9999	-0.62	67	67
THY1	0.001	0.076	-9999	-0.55	11	11
RhoA/GDP	0.008	0.018	-9999	-0.43	1	1
Lipoprotein(a)	-0.086	0.15	-9999	-0.31	178	178
alphaM/beta2 Integrin/LRP/tPA	-0.054	0.18	-9999	-0.47	75	75
IL6	-0.16	0.32	-9999	-0.77	102	102
ITGB2	-0.037	0.14	-9999	-0.53	45	45
elevation of cytosolic calcium ion concentration	-0.052	0.18	-9999	-0.45	78	78
alphaM/beta2 Integrin/JAM2/JAM3	-0.081	0.22	-9999	-0.51	99	99
JAM2	-0.05	0.18	-9999	-0.54	66	66
alphaM/beta2 Integrin/ICAM1	-0.064	0.19	-9999	-0.44	92	92
alphaM/beta2 Integrin/uPA/Plg	-0.078	0.2	-9999	-0.46	105	105
RhoA/GTP	-0.14	0.21	-9999	-0.48	114	114
positive regulation of phagocytosis	-0.13	0.21	-9999	-0.56	87	87
Ron/MSP	-0.019	0.12	-9999	-0.37	55	55
alphaM/beta2 Integrin/uPAR/uPA	-0.052	0.18	-9999	-0.46	78	78
alphaM/beta2 Integrin/uPAR	-0.058	0.18	-9999	-0.48	76	76
PLAU	-0.001	0.078	-9999	-0.5	14	14
PLAT	0	0.078	-9999	-0.54	12	12
actin filament polymerization	-0.13	0.19	-9999	-0.44	114	114
MST1	-0.033	0.15	-9999	-0.51	51	51
alphaM/beta2 Integrin/lipoprotein(a)	-0.13	0.2	-9999	-0.44	125	125
TNF	-0.11	0.26	-9999	-0.73	58	58
RAP1B	0.011	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.064	0.19	-9999	-0.48	85	85
fibrinolysis	-0.078	0.2	-9999	-0.45	105	105
HCK	-0.018	0.12	-9999	-0.55	31	31
dendritic cell antigen processing and presentation	-0.13	0.2	-9999	-0.45	125	125
VTN	-0.051	0.17	-9999	-0.5	71	71
alphaM/beta2 Integrin/CYR61	-0.077	0.2	-9999	-0.49	90	90
LPA	-0.026	0.12	-9999	-0.46	41	41
LRP1	0.006	0.057	-9999	-0.56	6	6
cell migration	-0.11	0.26	-9999	-0.57	111	111
FN1	-0.086	0.21	-9999	-0.52	109	109
alphaM/beta2 Integrin/Thy1	-0.063	0.19	-9999	-0.5	78	78
MPO	-0.039	0.16	-9999	-0.53	55	55
KNG1	-0.11	0.22	-9999	-0.52	136	136
RAP1/GDP	0.015	0.015	-9999	-0.36	1	1
ROCK1	-0.13	0.2	-9999	-0.46	116	116
ELA2	0	0	-9999	-10000	0	0
PLG	-0.036	0.15	-9999	-0.58	42	42
CTGF	-0.005	0.087	-9999	-0.46	21	21
alphaM/beta2 Integrin/Hck	-0.073	0.22	-9999	-0.54	83	83
ITGAM	-0.071	0.19	-9999	-0.52	84	84
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.11	0.24	-9999	-0.49	130	130
HP	-0.08	0.2	-9999	-0.5	103	103
leukocyte adhesion	-0.13	0.22	-9999	-0.59	85	85
SELP	-0.082	0.21	-9999	-0.55	99	99

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.067	0.18	-9999	-0.55	57	57
Syndecan-4/Syndesmos	-0.14	0.23	-9999	-0.56	102	102
positive regulation of JNK cascade	-0.14	0.22	-9999	-0.55	107	107
Syndecan-4/ADAM12	-0.18	0.27	-9999	-0.6	140	140
CCL5	-0.037	0.15	-9999	-0.51	55	55
Rac1/GDP	0.008	0	-9999	-10000	0	0
DNM2	0.01	0.024	-9999	-0.58	1	1
ITGA5	-0.005	0.09	-9999	-0.49	20	20
SDCBP	0	0.08	-9999	-0.58	11	11
PLG	-0.032	0.14	-9999	-0.56	42	42
ADAM12	-0.078	0.2	-9999	-0.51	101	101
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.01	0.027	-9999	-0.46	2	2
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.03	0.04	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.16	0.26	-9999	-0.59	127	127
Syndecan-4/CXCL12/CXCR4	-0.15	0.24	-9999	-0.58	106	106
Syndecan-4/Laminin alpha3	-0.15	0.24	-9999	-0.56	122	122
MDK	-0.009	0.1	-9999	-0.5	23	23
Syndecan-4/FZD7	-0.14	0.24	-9999	-0.57	104	104
Syndecan-4/Midkine	-0.14	0.24	-9999	-0.56	119	119
FZD7	-0.001	0.078	-9999	-0.5	14	14
Syndecan-4/FGFR1/FGF	-0.17	0.23	-9999	-0.56	118	118
THBS1	-0.004	0.088	-9999	-0.52	17	17
integrin-mediated signaling pathway	-0.16	0.25	-9999	-0.57	128	128
positive regulation of MAPKKK cascade	-0.14	0.22	-9999	-0.55	107	107
Syndecan-4/TACI	-0.17	0.25	-9999	-0.57	132	132
CXCR4	-0.016	0.11	-9999	-0.49	32	32
cell adhesion	-0.026	0.11	-9999	-0.32	57	57
Syndecan-4/Dynamin	-0.13	0.23	-9999	-0.55	113	113
Syndecan-4/TSP1	-0.14	0.24	-9999	-0.58	107	107
Syndecan-4/GIPC	-0.14	0.23	-9999	-0.55	114	114
Syndecan-4/RANTES	-0.16	0.24	-9999	-0.57	121	121
ITGB1	0.011	0	-9999	-10000	0	0
LAMA1	-0.055	0.18	-9999	-0.54	72	72
LAMA3	-0.016	0.12	-9999	-0.51	32	32
RAC1	0.011	0	-9999	-10000	0	0
PRKCA	0.038	0.055	-9999	-0.46	2	2
Syndecan-4/alpha-Actinin	-0.13	0.23	-9999	-0.55	113	113
TFPI	-0.008	0.1	-9999	-0.53	21	21
F2	-0.12	0.22	-9999	-0.5	146	146
alpha5/beta1 Integrin	0.005	0.065	-9999	-0.34	20	20
positive regulation of cell adhesion	-0.17	0.25	-9999	-0.59	126	126
ACTN1	0.011	0	-9999	-10000	0	0
TNC	-0.06	0.18	-9999	-0.52	80	80
Syndecan-4/CXCL12	-0.14	0.24	-9999	-0.56	122	122
FGF6	-0.001	0.019	-9999	-0.46	1	1
RHOA	0.01	0.024	-9999	-0.58	1	1
CXCL12	-0.013	0.11	-9999	-0.49	29	29
TNFRSF13B	-0.062	0.18	-9999	-0.52	80	80
FGF2	-0.039	0.16	-9999	-0.52	56	56
FGFR1	-0.009	0.1	-9999	-0.52	23	23
Syndecan-4/PI-4-5-P2	-0.14	0.23	-9999	-0.55	113	113
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.082	0.2	-9999	-0.51	109	109
cell migration	-0.006	0.017	-9999	-10000	0	0
PRKCD	0.016	0.009	-9999	-10000	0	0
vasculogenesis	-0.14	0.23	-9999	-0.53	119	119
SDC4	-0.15	0.24	-9999	-0.58	113	113
Syndecan-4/Tenascin C	-0.17	0.26	-9999	-0.59	128	128
Syndecan-4/PI-4-5-P2/PKC alpha	-0.024	0.032	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.14	0.23	-9999	-0.54	119	119
MMP9	-0.06	0.18	-9999	-0.52	79	79
Rac1/GTP	-0.027	0.12	-9999	-0.33	57	57
cytoskeleton organization	-0.13	0.22	-9999	-0.54	102	102
GIPC1	0.007	0.048	-9999	-0.58	4	4
Syndecan-4/TFPI	-0.14	0.24	-9999	-0.56	119	119

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.028	0.14	-10000	0	-0.42	46	46
fibroblast growth factor receptor signaling pathway	-0.028	0.14	-10000	0	-0.42	46	46
LAMA1	-0.055	0.18	-10000	0	-0.54	72	72
PRNP	-0.002	0.089	-10000	0	-0.57	14	14
GPC1/SLIT2	-0.093	0.18	-10000	0	-0.39	161	161
SMAD2	0.014	0.065	-10000	0	-0.33	17	17
GPC1/PrPc/Cu2+	-0.001	0.076	-10000	0	-0.34	28	28
GPC1/Laminin alpha1	-0.041	0.15	-10000	0	-0.4	82	82
TDGF1	-0.072	0.2	-10000	0	-0.58	84	84
CRIPTO/GPC1	-0.054	0.16	-10000	0	-0.42	98	98
APP/GPC1	0.007	0.065	-10000	0	-0.39	15	15
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.043	0.14	-10000	0	-0.36	98	98
FLT1	0.007	0.052	-10000	0	-0.56	5	5
GPC1/TGFB/TGFBR1/TGFBR2	0.012	0.062	-10000	0	-0.35	14	14
SERPINC1	-0.012	0.091	-10000	0	-0.46	24	24
FYN	-0.042	0.14	-10000	0	-0.35	103	103
FGR	-0.061	0.16	-10000	0	-0.36	128	128
positive regulation of MAPKKK cascade	-0.096	0.21	-10000	0	-0.47	123	123
SLIT2	-0.13	0.24	-10000	0	-0.53	152	152
GPC1/NRG	-0.05	0.15	-10000	0	-0.38	99	99
NRG1	-0.068	0.19	-10000	0	-0.53	87	87
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.012	0.066	-10000	0	-0.38	13	13
LYN	-0.038	0.14	-10000	0	-0.35	98	98
mol:Spermine	0	0.062	-10000	0	-0.4	14	14
cell growth	-0.028	0.14	-10000	0	-0.42	46	46
BMP signaling pathway	0.002	0.085	0.54	14	-10000	0	14
SRC	-0.039	0.14	-10000	0	-0.35	98	98
TGFBR1	0.007	0.048	-10000	0	-0.58	4	4
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.2	0.27	-10000	0	-0.53	233	233
GPC1	-0.002	0.085	-10000	0	-0.55	14	14
TGFBR1 (dimer)	0.007	0.048	-10000	0	-0.58	4	4
VEGFA	0.011	0.019	-10000	0	-0.46	1	1
BLK	-0.12	0.2	-10000	0	-0.38	201	201
HCK	-0.056	0.16	-10000	0	-0.36	121	121
FGF2	-0.039	0.16	-10000	0	-0.52	56	56
FGFR1	-0.009	0.1	-10000	0	-0.52	23	23
VEGFR1 homodimer	0.007	0.052	-10000	0	-0.56	5	5
TGFBR2	0.011	0.019	-10000	0	-0.46	1	1
cell death	0.007	0.065	-10000	0	-0.39	15	15
ATIII/GPC1	-0.009	0.089	-10000	0	-0.34	38	38
PLA2G2A/GPC1	-0.15	0.21	-10000	0	-0.39	238	238
LCK	-0.063	0.17	-10000	0	-0.38	128	128
neuron differentiation	-0.05	0.15	-10000	0	-0.38	99	99
PrPc/Cu2+	-0.002	0.065	-10000	0	-0.42	14	14
APP	0.01	0.024	-10000	0	-0.58	1	1
TGFBR2 (dimer)	0.011	0.019	-10000	0	-0.46	1	1

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.094	0.19	-10000	0	-0.54	78	78
FYN	-0.089	0.29	-10000	0	-0.7	87	87
LAT/GRAP2/SLP76	-0.11	0.23	-10000	0	-0.58	94	94
IKBKB	0.011	0.019	-10000	0	-0.46	1	1
AKT1	-0.051	0.19	-10000	0	-0.45	89	89
B2M	0.007	0.044	-10000	0	-0.52	4	4
IKBKG	-0.036	0.054	-10000	0	-0.16	72	72
MAP3K8	0.01	0.031	-10000	0	-0.52	2	2
mol:Ca2+	-0.024	0.04	-10000	0	-0.1	109	109
integrin-mediated signaling pathway	0.007	0.052	-10000	0	-0.32	14	14
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.09	0.28	-10000	0	-0.68	91	91
TRPV6	-0.094	0.19	-10000	0	-0.48	118	118
CD28	-0.034	0.15	-10000	0	-0.56	47	47
SHC1	-0.086	0.27	-10000	0	-0.68	84	84
receptor internalization	-0.095	0.3	-10000	0	-0.74	84	84
PRF1	-0.1	0.33	-10000	0	-1	55	55
KRAS	0.006	0.057	-10000	0	-0.56	6	6
GRB2	0.011	0	-10000	0	-10000	0	0
COT/AKT1	-0.033	0.15	-10000	0	-0.35	86	86
LAT	-0.094	0.28	-10000	0	-0.68	89	89
EntrezGene:6955	-0.001	0.004	-10000	0	-10000	0	0
CD3D	-0.03	0.15	-10000	0	-0.56	43	43
CD3E	-0.025	0.14	-10000	0	-0.56	38	38
CD3G	-0.054	0.18	-10000	0	-0.57	67	67
RASGRP2	-0.01	0.044	-10000	0	-0.17	33	33
RASGRP1	-0.055	0.2	-10000	0	-0.47	91	91
HLA-A	0.002	0.069	-10000	0	-0.52	10	10
RASSF5	-0.001	0.08	-10000	0	-0.53	13	13
RAP1A/GTP/RAPL	0.007	0.052	-10000	0	-0.33	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0	0.059	-10000	0	-0.12	77	77
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.065	0.096	-10000	0	-0.26	90	90
PRKCA	-0.049	0.1	-10000	0	-0.28	75	75
GRAP2	-0.024	0.14	-10000	0	-0.55	37	37
mol:IP3	-0.058	0.19	0.2	74	-0.44	87	161
EntrezGene:6957	-0.001	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.088	0.29	-10000	0	-0.75	74	74
ORAI1	0.055	0.11	0.27	115	-0.33	1	116
CSK	-0.089	0.28	-10000	0	-0.72	80	80
B7 family/CD28	-0.12	0.32	-10000	0	-0.72	108	108
CHUK	0.007	0.048	-10000	0	-0.58	4	4
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.11	0.33	-10000	0	-0.79	89	89
PTPN6	-0.09	0.28	-10000	0	-0.71	82	82
VAV1	-0.099	0.29	-10000	0	-0.7	92	92
Monovalent TCR/CD3	-0.067	0.26	-10000	0	-0.6	83	83
CBL	0.011	0	-10000	0	-10000	0	0
LCK	-0.099	0.3	-10000	0	-0.73	88	88
PAG1	-0.091	0.28	-10000	0	-0.71	82	82
RAP1A	0.01	0.024	-10000	0	-0.58	1	1
TCR/CD3/MHC I/CD8/LCK	-0.11	0.33	-10000	0	-0.8	87	87
CD80	-0.039	0.16	-10000	0	-0.56	52	52
CD86	-0.036	0.16	-10000	0	-0.54	51	51
PDK1/CARD11/BCL10/MALT1	-0.079	0.12	-10000	0	-0.32	92	92
HRAS	0.008	0.041	-10000	0	-0.49	4	4
GO:0035030	-0.09	0.25	-10000	0	-0.58	107	107
CD8A	-0.06	0.19	-10000	0	-0.54	78	78
CD8B	-0.045	0.17	-10000	0	-0.56	59	59
PTPRC	-0.043	0.17	-10000	0	-0.55	58	58
PDK1/PKC theta	-0.069	0.23	-10000	0	-0.56	90	90
CSK/PAG1	-0.084	0.27	-10000	0	-0.69	81	81
SOS1	0.01	0.024	-10000	0	-0.58	1	1
peptide-MHC class I	0.006	0.06	-10000	0	-0.38	14	14
GRAP2/SLP76	-0.12	0.27	-10000	0	-0.68	93	93
STIM1	0.03	0.053	-10000	0	-10000	0	0
RAS family/GTP	-0.003	0.083	-10000	0	-0.19	58	58
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.11	0.33	-10000	0	-0.82	84	84
mol:DAG	-0.068	0.15	0.13	1	-0.38	92	93
RAP1A/GDP	0.001	0.027	-10000	0	-0.15	1	1
PLCG1	0.01	0.024	-10000	0	-0.58	1	1
CD247	-0.02	0.13	-10000	0	-0.55	33	33
cytotoxic T cell degranulation	-0.096	0.31	-10000	0	-0.94	56	56
RAP1A/GTP	-0.006	0.015	-10000	0	-0.069	28	28
mol:PI-3-4-5-P3	-0.068	0.22	-10000	0	-0.54	90	90
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.083	0.24	0.22	65	-0.58	88	153
NRAS	0.001	0.076	-10000	0	-0.58	10	10
ZAP70	-0.036	0.15	-10000	0	-0.53	52	52
GRB2/SOS1	0.016	0.018	-10000	0	-0.42	1	1
LAT/GRAP2/SLP76/VAV1	-0.11	0.22	-10000	0	-0.56	97	97
MALT1	0.006	0.054	-10000	0	-0.58	5	5
TRAF6	0.01	0.024	-10000	0	-0.58	1	1
CD8 heterodimer	-0.074	0.2	-10000	0	-0.46	115	115
CARD11	-0.12	0.22	-10000	0	-0.49	153	153
PRKCB	-0.062	0.13	-10000	0	-0.34	85	85
PRKCE	-0.048	0.1	-10000	0	-0.28	75	75
PRKCQ	-0.088	0.27	-10000	0	-0.64	93	93
LCP2	-0.014	0.12	-10000	0	-0.54	27	27
BCL10	0.007	0.048	-10000	0	-0.58	4	4
regulation of survival gene product expression	-0.04	0.16	-10000	0	-0.38	89	89
IKK complex	0.005	0.056	-10000	0	-0.12	58	58
RAS family/GDP	-0.007	0.016	-10000	0	-0.089	12	12
MAP3K14	-0.018	0.12	-10000	0	-0.28	72	72
PDPK1	-0.046	0.18	-10000	0	-0.42	89	89
TCR/CD3/MHC I/CD8/Fyn	-0.11	0.34	-10000	0	-0.79	92	92

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.008	0.041	-9999	-0.49	4	4
EGFR	0.004	0.063	-9999	-0.53	8	8
EGF/EGFR	-0.12	0.15	-9999	-0.34	129	129
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.071	0.14	-9999	-0.29	94	94
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.019	0.12	-9999	-0.52	34	34
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.18	0.25	-9999	-0.51	216	216
EGF/EGFR dimer/SHC	-0.099	0.16	-9999	-0.3	223	223
mol:GDP	-0.072	0.14	-9999	-0.29	94	94
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.022	0.13	-9999	-0.52	38	38
GRB2/SOS1	0.016	0.018	-9999	-0.42	1	1
HRAS/GTP	-0.084	0.11	-9999	-0.45	3	3
SHC1	0.011	0	-9999	-10000	0	0
HRAS/GDP	-0.086	0.11	-9999	-0.46	3	3
FRAP1	-0.07	0.13	-9999	-0.28	94	94
EGF/EGFR dimer	-0.13	0.19	-9999	-0.36	223	223
SOS1	0.01	0.024	-9999	-0.58	1	1
GRB2	0.011	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.029	0.13	-9999	-0.38	69	69

×

IL12-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.067	0.19	-10000	0	-0.45	76	76
TBX21	-0.24	0.51	-10000	0	-1.1	125	125
B2M	0.004	0.045	-10000	0	-0.52	4	4
TYK2	0.007	0.034	-10000	0	-0.61	1	1
IL12RB1	-0.037	0.16	-10000	0	-0.57	48	48
GADD45B	-0.15	0.37	-10000	0	-0.89	77	77
IL12RB2	-0.038	0.16	-10000	0	-0.53	53	53
GADD45G	-0.15	0.38	-10000	0	-0.86	91	91
natural killer cell activation	-0.003	0.023	-10000	0	-10000	0	0
RELB	0.009	0.036	-10000	0	-0.5	3	3
RELA	0.011	0	-10000	0	-10000	0	0
IL18	0.003	0.069	-10000	0	-0.55	9	9
IL2RA	-0.045	0.17	-10000	0	-0.55	60	60
IFNG	-0.066	0.18	-10000	0	-0.51	86	86
STAT3 (dimer)	-0.15	0.36	-10000	0	-0.77	115	115
HLA-DRB5	-0.081	0.2	-10000	0	-0.52	103	103
FASLG	-0.24	0.51	-10000	0	-1.1	122	122
NF kappa B2 p52/RelB	-0.26	0.4	-10000	0	-0.92	131	131
CD4	-0.014	0.12	-10000	0	-0.55	27	27
SOCS1	-0.028	0.14	-10000	0	-0.49	47	47
EntrezGene:6955	-0.004	0.015	-10000	0	-10000	0	0
CD3D	-0.033	0.15	-10000	0	-0.56	43	43
CD3E	-0.028	0.14	-10000	0	-0.56	38	38
CD3G	-0.057	0.18	-10000	0	-0.57	67	67
IL12Rbeta2/JAK2	-0.034	0.14	-10000	0	-0.4	72	72
CCL3	-0.24	0.5	-10000	0	-1.1	110	110
CCL4	-0.22	0.49	-10000	0	-1.1	112	112
HLA-A	-0.001	0.069	-10000	0	-0.52	10	10
IL18/IL18R	-0.012	0.15	-10000	0	-0.38	70	70
NOS2	-0.27	0.55	-10000	0	-1.2	128	128
IL12/IL12R/TYK2/JAK2/SPHK2	-0.052	0.16	-10000	0	-0.43	57	57
IL1R1	-0.21	0.46	-10000	0	-1	109	109
IL4	0.004	0.024	-10000	0	-10000	0	0
JAK2	-0.012	0.11	-10000	0	-0.57	21	21
EntrezGene:6957	-0.004	0.015	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.18	0.45	-10000	0	-0.96	115	115
RAB7A	-0.11	0.32	-10000	0	-0.81	50	50
lysosomal transport	-0.1	0.3	-10000	0	-0.75	51	51
FOS	-0.17	0.41	-10000	0	-1.1	77	77
STAT4 (dimer)	-0.17	0.41	-10000	0	-0.9	109	109
STAT5A (dimer)	-0.29	0.42	-10000	0	-0.93	147	147
GZMA	-0.23	0.5	-10000	0	-1.1	121	121
GZMB	-0.24	0.51	-10000	0	-1.1	129	129
HLX	0.006	0.055	-10000	0	-0.54	6	6
LCK	-0.24	0.51	-10000	0	-1.1	128	128
TCR/CD3/MHC II/CD4	-0.12	0.34	-10000	0	-0.75	94	94
IL2/IL2R	-0.032	0.15	-10000	0	-0.41	65	65
MAPK14	-0.15	0.38	-10000	0	-0.86	93	93
CCR5	-0.17	0.42	-10000	0	-0.94	99	99
IL1B	-0.064	0.19	-10000	0	-0.53	80	80
STAT6	-0.036	0.12	0.2	10	-0.25	44	54
STAT4	-0.027	0.14	-10000	0	-0.56	40	40
STAT3	0.011	0	-10000	0	-10000	0	0
STAT1	0.006	0.051	-10000	0	-0.5	6	6
NFKB1	0.01	0.024	-10000	0	-0.58	1	1
NFKB2	0.01	0.031	-10000	0	-0.52	2	2
IL12B	-0.006	0.075	-10000	0	-0.47	14	14
CD8A	-0.063	0.19	-10000	0	-0.54	78	78
CD8B	-0.048	0.17	-10000	0	-0.56	59	59
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.066	0.19	0.45	76	-10000	0	76
IL2RB	-0.017	0.12	-10000	0	-0.55	30	30
proteasomal ubiquitin-dependent protein catabolic process	-0.15	0.37	-10000	0	-0.8	109	109
IL2RG	-0.001	0.084	-10000	0	-0.56	13	13
IL12	-0.029	0.13	-10000	0	-0.4	60	60
STAT5A	0.011	0	-10000	0	-10000	0	0
CD247	-0.023	0.13	-10000	0	-0.55	33	33
IL2	0.001	0.027	-10000	0	-0.46	2	2
SPHK2	0.009	0.036	-10000	0	-0.5	3	3
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.038	0.16	-10000	0	-0.57	47	47
IL12/IL12R/TYK2/JAK2	-0.26	0.58	-10000	0	-1.1	131	131
MAP2K3	-0.15	0.38	-10000	0	-0.85	98	98
RIPK2	0.011	0	-10000	0	-10000	0	0
MAP2K6	-0.16	0.39	-10000	0	-0.87	98	98
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.042	0.16	-10000	0	-0.52	60	60
IL18RAP	-0.034	0.16	-10000	0	-0.55	48	48
IL12Rbeta1/TYK2	-0.022	0.13	-10000	0	-0.43	49	49
EOMES	-0.14	0.41	-10000	0	-1.3	61	61
STAT1 (dimer)	-0.18	0.38	-10000	0	-0.81	123	123
T cell proliferation	-0.11	0.3	0.4	1	-0.64	106	107
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.012	0.12	-10000	0	-0.56	25	25
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.19	0.28	-10000	0	-0.7	110	110
ATF2	-0.13	0.35	-10000	0	-0.79	91	91

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.003	0.088	-9999	-0.55	15	15
CCL5	-0.037	0.15	-9999	-0.51	55	55
SDCBP	0	0.08	-9999	-0.58	11	11
FGFR/FGF2/Syndecan-1	-0.12	0.19	-9999	-0.52	68	68
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.12	0.2	-9999	-0.48	98	98
Syndecan-1/Syntenin	-0.11	0.19	-9999	-0.49	77	77
MAPK3	-0.085	0.17	-9999	-0.5	49	49
HGF/MET	-0.02	0.12	-9999	-0.39	54	54
TGFB1/TGF beta receptor Type II	-0.003	0.088	-9999	-0.55	15	15
BSG	0.01	0.024	-9999	-0.58	1	1
keratinocyte migration	-0.12	0.2	-9999	-0.47	98	98
Syndecan-1/RANTES	-0.13	0.2	-9999	-0.49	100	100
Syndecan-1/CD147	-0.094	0.18	-9999	-0.47	68	68
Syndecan-1/Syntenin/PIP2	-0.11	0.18	-9999	-0.47	77	77
LAMA5	-0.031	0.15	-9999	-0.57	43	43
positive regulation of cell-cell adhesion	-0.1	0.18	-9999	-0.46	77	77
MMP7	-0.14	0.24	-9999	-0.52	167	167
HGF	-0.037	0.16	-9999	-0.54	52	52
Syndecan-1/CASK	-0.11	0.18	-9999	-0.5	68	68
Syndecan-1/HGF/MET	-0.12	0.21	-9999	-0.5	92	92
regulation of cell adhesion	-0.077	0.16	-9999	-0.48	49	49
HPSE	-0.005	0.092	-9999	-0.51	19	19
positive regulation of cell migration	-0.12	0.19	-9999	-0.52	68	68
SDC1	-0.12	0.19	-9999	-0.52	68	68
Syndecan-1/Collagen	-0.12	0.19	-9999	-0.52	68	68
PPIB	0.011	0	-9999	-10000	0	0
MET	0.01	0.031	-9999	-0.52	2	2
PRKACA	0.011	0	-9999	-10000	0	0
MMP9	-0.059	0.18	-9999	-0.52	79	79
MAPK1	-0.085	0.17	-9999	-0.46	62	62
homophilic cell adhesion	-0.11	0.19	-9999	-0.51	68	68
MMP1	-0.12	0.24	-9999	-0.53	151	151

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.28	0.36	-10000	0	-0.97	73	73
PCK1	-0.27	0.45	-10000	0	-1.3	75	75
HNF4A	-0.36	0.44	-10000	0	-1.1	115	115
KCNJ11	-0.27	0.37	-10000	0	-1	68	68
AKT1	-0.14	0.16	-10000	0	-0.43	39	39
response to starvation	-0.019	0.035	-10000	0	-10000	0	0
DLK1	-0.28	0.37	-10000	0	-0.97	78	78
NKX2-1	-0.18	0.34	-10000	0	-1.1	47	47
ACADM	-0.29	0.38	-10000	0	-0.98	85	85
TAT	-0.18	0.22	-10000	0	-0.74	31	31
CEBPB	0.004	0.042	-10000	0	-0.49	4	4
CEBPA	-0.008	0.098	-10000	0	-0.58	17	17
TTR	-0.29	0.41	-10000	0	-1	104	104
PKLR	-0.43	0.48	-10000	0	-1	190	190
APOA1	-0.38	0.48	-10000	0	-1.2	102	102
CPT1C	-0.3	0.39	-10000	0	-1	95	95
ALAS1	-0.12	0.18	-10000	0	-0.81	3	3
TFRC	-0.18	0.28	-10000	0	-0.92	31	31
FOXF1	0.013	0.11	0.28	7	-0.56	16	23
NF1	0.014	0.042	-10000	0	-0.58	3	3
HNF1A (dimer)	0.002	0.072	-10000	0	-0.53	7	7
CPT1A	-0.28	0.36	-10000	0	-0.94	81	81
HMGCS1	-0.28	0.37	-10000	0	-0.97	82	82
NR3C1	-0.037	0.13	-10000	0	-0.54	29	29
CPT1B	-0.3	0.38	-10000	0	-0.97	98	98
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.007	0.044	-10000	0	-0.58	1	1
GCK	-0.3	0.39	-10000	0	-0.98	94	94
CREB1	-0.008	0.062	-10000	0	-0.6	2	2
IGFBP1	-0.27	0.4	-10000	0	-1	92	92
PDX1	-0.18	0.35	-10000	0	-1.4	37	37
UCP2	-0.29	0.37	-10000	0	-0.98	82	82
ALDOB	-0.38	0.48	-10000	0	-1.2	130	130
AFP	-0.069	0.17	-10000	0	-0.48	55	55
BDH1	-0.28	0.37	-10000	0	-0.97	80	80
HADH	-0.26	0.36	-10000	0	-0.97	71	71
F2	-0.41	0.52	-10000	0	-1.3	120	120
HNF1A	0.002	0.072	-10000	0	-0.53	7	7
G6PC	-0.032	0.14	-10000	0	-0.81	6	6
SLC2A2	-0.17	0.24	-10000	0	-0.78	28	28
INS	0.016	0.065	-10000	0	-0.46	3	3
FOXA1	-0.07	0.21	0.29	1	-0.56	79	80
FOXA3	-0.033	0.13	-10000	0	-0.5	22	22
FOXA2	-0.31	0.41	-10000	0	-1	89	89
ABCC8	-0.29	0.39	-10000	0	-1	81	81
ALB	-0.076	0.18	-10000	0	-0.53	41	41

×

Signaling events mediated by the Hedgehog family

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.05	0.22	-10000	0	-0.63	52	52
IHH	-0.039	0.17	-10000	0	-0.62	43	43
SHH Np/Cholesterol/GAS1	-0.08	0.16	-10000	0	-0.3	185	185
LRPAP1	0.01	0.024	-10000	0	-0.58	1	1
dorsoventral neural tube patterning	0.08	0.16	0.3	185	-10000	0	185
SMO/beta Arrestin2	-0.036	0.19	-10000	0	-0.63	36	36
SMO	-0.044	0.2	-10000	0	-0.57	54	54
AKT1	-0.005	0.11	-10000	0	-0.46	14	14
ARRB2	0.011	0	-10000	0	-10000	0	0
BOC	-0.034	0.14	-10000	0	-0.48	55	55
ADRBK1	0.01	0.031	-10000	0	-0.52	2	2
heart looping	-0.043	0.2	-10000	0	-0.56	54	54
STIL	-0.026	0.16	-10000	0	-0.59	29	29
DHH N/PTCH2	-0.041	0.15	-10000	0	-0.43	77	77
DHH N/PTCH1	-0.047	0.17	-10000	0	-0.53	31	31
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
DHH	-0.03	0.14	-10000	0	-0.54	44	44
PTHLH	-0.075	0.29	-10000	0	-0.92	51	51
determination of left/right symmetry	-0.043	0.2	-10000	0	-0.56	54	54
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
skeletal system development	-0.074	0.29	-10000	0	-0.91	51	51
IHH N/Hhip	-0.084	0.2	-10000	0	-0.46	126	126
DHH N/Hhip	-0.079	0.19	-10000	0	-0.42	131	131
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.043	0.2	-10000	0	-0.56	54	54
pancreas development	-0.08	0.21	-10000	0	-0.54	98	98
HHAT	0.004	0.064	-10000	0	-0.58	7	7
PI3K	0.013	0.04	-10000	0	-0.42	5	5
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.13	0.24	-10000	0	-0.52	160	160
somite specification	-0.043	0.2	-10000	0	-0.56	54	54
SHH Np/Cholesterol/PTCH1	-0.032	0.17	-10000	0	-0.6	31	31
SHH Np/Cholesterol/PTCH2	-0.023	0.12	-10000	0	-0.32	77	77
SHH Np/Cholesterol/Megalin	-0.023	0.11	-10000	0	-0.29	76	76
SHH	-0.009	0.11	-10000	0	-0.41	38	38
catabolic process	-0.032	0.16	-10000	0	-0.44	54	54
SMO/Vitamin D3	-0.039	0.19	-10000	0	-0.63	39	39
SHH Np/Cholesterol/Hhip	-0.053	0.15	-10000	0	-0.33	124	124
LRP2	-0.028	0.12	-10000	0	-0.46	43	43
receptor-mediated endocytosis	-0.043	0.19	-10000	0	-0.6	41	41
SHH Np/Cholesterol/BOC	-0.026	0.12	-10000	0	-0.3	87	87
SHH Np/Cholesterol/CDO	-0.008	0.1	-10000	0	-0.34	47	47
mesenchymal cell differentiation	0.053	0.15	0.33	124	-10000	0	124
mol:Vitamin D3	-0.03	0.17	-10000	0	-0.61	31	31
IHH N/PTCH2	-0.043	0.16	-10000	0	-0.44	78	78
CDON	-0.001	0.081	-10000	0	-0.52	14	14
IHH N/PTCH1	-0.031	0.16	-10000	0	-0.44	54	54
Megalin/LRPAP1	-0.012	0.087	-10000	0	-0.32	44	44
PTCH2	-0.028	0.14	-10000	0	-0.54	42	42
SHH Np/Cholesterol	-0.008	0.082	-10000	0	-0.32	38	38
PTCH1	-0.032	0.16	-10000	0	-0.44	54	54
HHIP	-0.08	0.21	-10000	0	-0.54	98	98

×

TCGA08_retinoblastoma

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
CDKN2B	-0.013	0.1	-10000	0	-0.51	25	25
CDKN2C	0.018	0.017	-10000	0	-10000	0	0
CDKN2A	-0.07	0.19	-10000	0	-0.5	94	94
CCND2	0.019	0.072	0.2	55	-0.13	26	81
RB1	-0.016	0.077	-10000	0	-0.21	60	60
CDK4	0.027	0.075	0.22	53	-10000	0	53
CDK6	0.026	0.076	0.22	55	-10000	0	55
G1/S progression	0.016	0.077	0.21	60	-10000	0	60

×

BCR signaling pathway

Figure S17. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S17. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.062	0.16	-10000	0	-0.41	80	80
IKBKB	-0.029	0.09	-10000	0	-0.24	42	42
AKT1	-0.051	0.11	0.21	1	-0.25	91	92
IKBKG	-0.03	0.097	0.16	13	-0.26	43	56
CALM1	-0.041	0.16	0.25	21	-0.47	47	68
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
MAP3K1	-0.11	0.24	-10000	0	-0.57	99	99
MAP3K7	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	-0.049	0.17	0.26	21	-0.5	50	71
DOK1	0.011	0	-10000	0	-10000	0	0
AP-1	-0.023	0.099	0.2	17	-0.25	48	65
LYN	0.011	0	-10000	0	-10000	0	0
BLNK	-0.01	0.11	-10000	0	-0.58	21	21
SHC1	0.011	0	-10000	0	-10000	0	0
BCR complex	-0.097	0.22	-10000	0	-0.47	140	140
CD22	-0.16	0.28	-10000	0	-0.69	99	99
CAMK2G	-0.032	0.15	0.24	21	-0.44	46	67
CSNK2A1	0.011	0	-10000	0	-10000	0	0
INPP5D	-0.017	0.13	-10000	0	-0.58	28	28
SHC/GRB2/SOS1	-0.076	0.14	-10000	0	-0.46	42	42
GO:0007205	-0.05	0.17	0.26	21	-0.5	50	71
SYK	0.011	0.019	-10000	0	-0.46	1	1
ELK1	-0.042	0.16	0.24	20	-0.48	48	68
NFATC1	-0.1	0.21	-10000	0	-0.5	94	94
B-cell antigen/BCR complex	-0.097	0.22	-10000	0	-0.47	140	140
PAG1/CSK	0.011	0.048	-10000	0	-0.4	8	8
NFKBIB	-0.002	0.033	0.084	13	-0.12	2	15
HRAS	-0.039	0.15	0.23	21	-0.43	50	71
NFKBIA	-0.001	0.032	0.084	13	-0.12	2	15
NF-kappa-B/RelA/I kappa B beta	0.005	0.028	0.085	13	-0.17	1	14
RasGAP/Csk	-0.1	0.22	-10000	0	-0.44	138	138
mol:GDP	-0.045	0.16	0.26	21	-0.48	49	70
PTEN	0.005	0.059	-10000	0	-0.58	6	6
CD79B	-0.028	0.14	-10000	0	-0.52	44	44
NF-kappa-B/RelA/I kappa B alpha	0.005	0.028	0.085	13	-0.17	1	14
GRB2	0.011	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.11	0.22	-10000	0	-0.54	94	94
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
mol:IP3	-0.051	0.17	0.26	21	-0.51	50	71
CSK	0.01	0.024	-10000	0	-0.58	1	1
FOS	-0.051	0.16	0.24	18	-0.46	54	72
CHUK	-0.031	0.099	-10000	0	-0.27	43	43
IBTK	0.001	0.076	-10000	0	-0.58	10	10
CARD11/BCL10/MALT1/TAK1	-0.1	0.16	-10000	0	-0.46	77	77
PTPN6	-0.13	0.27	-10000	0	-0.67	91	91
RELA	0.011	0	-10000	0	-10000	0	0
BCL2A1	-0.002	0.036	-10000	0	-0.1	39	39
VAV2	-0.15	0.29	-10000	0	-0.66	111	111
ubiquitin-dependent protein catabolic process	0.002	0.032	0.086	13	-0.11	2	15
BTK	-0.055	0.27	0.36	25	-1.1	35	60
CD19	-0.17	0.28	-10000	0	-0.64	115	115
MAP4K1	-0.044	0.17	-10000	0	-0.55	59	59
CD72	-0.005	0.09	-10000	0	-0.5	19	19
PAG1	0.005	0.06	-10000	0	-0.55	7	7
MAPK14	-0.088	0.2	-10000	0	-0.48	94	94
SH3BP5	0.002	0.072	-10000	0	-0.58	9	9
PIK3AP1	-0.053	0.17	0.3	2	-0.54	47	49
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.075	0.23	-10000	0	-0.52	93	93
RAF1	-0.031	0.14	0.22	21	-0.45	37	58
RasGAP/p62DOK/SHIP	-0.13	0.2	-10000	0	-0.59	69	69
CD79A	-0.11	0.23	-10000	0	-0.54	134	134
re-entry into mitotic cell cycle	-0.023	0.099	0.2	17	-0.25	48	65
RASA1	0.009	0.034	-10000	0	-0.58	2	2
MAPK3	-0.015	0.12	0.22	2	-0.41	27	29
MAPK1	-0.015	0.12	0.22	19	-0.41	27	46
CD72/SHP1	-0.12	0.26	-10000	0	-0.65	88	88
NFKB1	0.01	0.024	-10000	0	-0.58	1	1
MAPK8	-0.089	0.2	-10000	0	-0.48	92	92
actin cytoskeleton organization	-0.12	0.24	-10000	0	-0.57	100	100
NF-kappa-B/RelA	0.014	0.053	0.17	13	-0.22	2	15
Calcineurin	-0.053	0.12	-10000	0	-0.47	31	31
PI3K	-0.15	0.21	-10000	0	-0.53	111	111
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.055	0.17	0.31	2	-0.52	50	52
SOS1	0.01	0.024	-10000	0	-0.58	1	1
Bam32/HPK1	-0.15	0.33	-10000	0	-0.85	95	95
DAPP1	-0.17	0.36	-10000	0	-1.1	73	73
cytokine secretion	-0.092	0.2	-10000	0	-0.46	95	95
mol:DAG	-0.051	0.17	0.26	21	-0.51	50	71
PLCG2	-0.011	0.11	-10000	0	-0.54	24	24
MAP2K1	-0.023	0.13	0.22	5	-0.44	31	36
B-cell antigen/BCR complex/FcgammaRIIB	-0.13	0.25	-10000	0	-0.43	202	202
mol:PI-3-4-5-P3	-0.1	0.14	0.28	1	-0.36	108	109
ETS1	-0.027	0.14	0.24	21	-0.46	36	57
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.064	0.18	-10000	0	-0.53	42	42
B-cell antigen/BCR complex/LYN	-0.12	0.25	-10000	0	-0.53	114	114
MALT1	0.006	0.054	-10000	0	-0.58	5	5
TRAF6	0.01	0.024	-10000	0	-0.58	1	1
RAC1	-0.13	0.26	-10000	0	-0.62	100	100
B-cell antigen/BCR complex/LYN/SYK	-0.14	0.25	-10000	0	-0.67	90	90
CARD11	-0.1	0.21	0.25	17	-0.5	94	111
FCGR2B	-0.084	0.21	-10000	0	-0.53	104	104
PPP3CA	0.011	0	-10000	0	-10000	0	0
BCL10	0.007	0.048	-10000	0	-0.58	4	4
IKK complex	-0.006	0.041	0.091	13	-0.11	12	25
PTPRC	-0.043	0.17	-10000	0	-0.54	58	58
PDPK1	-0.053	0.11	0.19	1	-0.25	89	90
PPP3CB	0.011	0	-10000	0	-10000	0	0
PPP3CC	0.005	0.059	-10000	0	-0.58	6	6
POU2F2	0.004	0.028	-10000	0	-0.099	17	17

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.034	0.23	0.27	34	-0.6	52	86
PTK2B	0.01	0.034	-10000	0	-0.58	2	2
mol:Ca2+	-0.024	0.25	-10000	0	-0.9	35	35
EDN1	-0.022	0.17	-10000	0	-0.44	55	55
EDN3	-0.095	0.22	-10000	0	-0.55	112	112
EDN2	-0.065	0.19	-10000	0	-0.52	85	85
HRAS/GDP	-0.043	0.19	-10000	0	-0.51	51	51
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.021	0.17	-10000	0	-0.46	46	46
ADCY4	-0.048	0.2	-10000	0	-0.54	57	57
ADCY5	-0.1	0.23	-10000	0	-0.53	91	91
ADCY6	-0.044	0.2	-10000	0	-0.53	54	54
ADCY7	-0.046	0.2	-10000	0	-0.53	56	56
ADCY1	-0.071	0.21	-10000	0	-0.54	68	68
ADCY2	-0.07	0.23	-10000	0	-0.59	69	69
ADCY3	-0.045	0.2	-10000	0	-0.53	54	54
ADCY8	-0.056	0.2	-10000	0	-0.55	54	54
ADCY9	-0.046	0.2	-10000	0	-0.54	54	54
arachidonic acid secretion	-0.065	0.2	-10000	0	-0.54	56	56
ETB receptor/Endothelin-1/Gq/GTP	-0.011	0.14	-10000	0	-0.42	37	37
GNAO1	-0.046	0.16	-10000	0	-0.49	68	68
HRAS	0.008	0.041	-10000	0	-0.49	4	4
ETA receptor/Endothelin-1/G12/GTP	-0.03	0.23	0.3	104	-0.57	50	154
ETA receptor/Endothelin-1/Gs/GTP	-0.045	0.23	0.28	96	-0.55	57	153
mol:GTP	0.001	0.004	-10000	0	-10000	0	0
COL3A1	-0.055	0.28	-10000	0	-0.74	63	63
EDNRB	-0.01	0.11	-10000	0	-0.57	20	20
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.069	0.29	-10000	0	-0.66	85	85
CYSLTR1	-0.062	0.29	-10000	0	-0.71	74	74
SLC9A1	-0.025	0.12	0.19	48	-0.32	46	94
mol:GDP	-0.051	0.2	-10000	0	-0.52	60	60
SLC9A3	-0.16	0.32	-10000	0	-0.63	151	151
RAF1	-0.047	0.18	-10000	0	-0.49	48	48
JUN	-0.007	0.2	-10000	0	-0.7	30	30
JAK2	-0.046	0.24	-10000	0	-0.61	60	60
mol:IP3	-0.023	0.17	-10000	0	-0.47	44	44
ETA receptor/Endothelin-1	-0.045	0.28	0.35	104	-0.65	60	164
PLCB1	-0.032	0.15	-10000	0	-0.56	45	45
PLCB2	0.004	0.062	-10000	0	-0.52	8	8
ETA receptor/Endothelin-3	-0.096	0.21	-10000	0	-0.45	132	132
FOS	-0.051	0.23	-10000	0	-0.87	31	31
Gai/GDP	-0.026	0.17	-10000	0	-0.84	19	19
CRK	0.011	0.019	-10000	0	-0.46	1	1
mol:Ca ++	-0.052	0.26	-10000	0	-0.65	65	65
BCAR1	0.008	0.044	-10000	0	-0.52	4	4
PRKCB1	-0.022	0.16	-10000	0	-0.45	43	43
GNAQ	0.006	0.059	-10000	0	-0.58	6	6
GNAZ	-0.012	0.11	-10000	0	-0.55	25	25
GNAL	-0.02	0.12	-10000	0	-0.5	36	36
Gs family/GDP	-0.09	0.16	-10000	0	-0.48	67	67
ETA receptor/Endothelin-1/Gq/GTP	-0.014	0.18	-10000	0	-0.5	42	42
MAPK14	-0.012	0.13	-10000	0	-0.46	28	28
TRPC6	-0.029	0.27	-10000	0	-0.99	34	34
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	-0.003	0.089	-10000	0	-0.56	15	15
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.019	0.14	-10000	0	-0.41	41	41
ETB receptor/Endothelin-2	-0.054	0.16	-10000	0	-0.38	104	104
ETB receptor/Endothelin-3	-0.075	0.18	-10000	0	-0.41	129	129
ETB receptor/Endothelin-1	-0.02	0.16	-10000	0	-0.42	55	55
MAPK3	-0.05	0.22	-10000	0	-0.69	41	41
MAPK1	-0.05	0.22	-10000	0	-0.7	40	40
Rac1/GDP	-0.041	0.18	-10000	0	-0.51	49	49
cAMP biosynthetic process	-0.073	0.21	-10000	0	-0.56	61	61
MAPK8	-0.018	0.22	-10000	0	-0.68	42	42
SRC	0.01	0.024	-10000	0	-0.58	1	1
ETB receptor/Endothelin-1/Gi/GTP	-0.02	0.12	-10000	0	-0.44	26	26
p130Cas/CRK/Src/PYK2	-0.052	0.21	-10000	0	-0.62	46	46
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.041	0.18	-10000	0	-0.5	51	51
COL1A2	-0.06	0.32	-10000	0	-0.81	64	64
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.074	0.18	-10000	0	-0.41	112	112
mol:DAG	-0.023	0.17	-10000	0	-0.47	44	44
MAP2K2	-0.045	0.19	-10000	0	-0.55	44	44
MAP2K1	-0.045	0.19	-10000	0	-0.55	45	45
EDNRA	-0.022	0.19	-10000	0	-0.52	49	49
positive regulation of muscle contraction	-0.023	0.2	-10000	0	-0.56	47	47
Gq family/GDP	-0.08	0.17	-10000	0	-0.56	46	46
HRAS/GTP	-0.051	0.18	-10000	0	-0.47	60	60
PRKCH	-0.02	0.16	-10000	0	-0.47	44	44
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCA	-0.018	0.16	-10000	0	-0.47	37	37
PRKCB	-0.042	0.2	-10000	0	-0.5	64	64
PRKCE	-0.016	0.16	-10000	0	-0.48	34	34
PRKCD	-0.017	0.16	-10000	0	-0.47	37	37
PRKCG	-0.095	0.2	-10000	0	-0.48	70	70
regulation of vascular smooth muscle contraction	-0.061	0.26	-10000	0	-1	31	31
PRKCQ	-0.045	0.19	-10000	0	-0.49	55	55
PLA2G4A	-0.072	0.22	-10000	0	-0.59	56	56
GNA14	-0.006	0.1	-10000	0	-0.56	19	19
GNA15	-0.008	0.1	-10000	0	-0.54	21	21
GNA12	0.011	0	-10000	0	-10000	0	0
GNA11	0.007	0.05	-10000	0	-0.54	5	5
Rac1/GTP	-0.03	0.23	0.3	104	-0.58	49	153
MMP1	-0.15	0.36	0.31	5	-0.71	151	156

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.01	0.031	-10000	0	-0.52	2	2
EPHB2	0	0.08	-10000	0	-0.55	12	12
EFNB1	0.005	0.07	-10000	0	-0.36	21	21
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.063	0.15	-10000	0	-0.48	34	34
Ephrin B2/EPHB1-2	-0.05	0.13	-10000	0	-0.32	61	61
neuron projection morphogenesis	-0.083	0.13	-10000	0	-0.46	34	34
Ephrin B1/EPHB1-2/Tiam1	-0.072	0.16	-10000	0	-0.5	37	37
DNM1	-0.006	0.093	-10000	0	-0.5	20	20
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.081	0.23	-10000	0	-0.66	80	80
YES1	-0.12	0.3	-10000	0	-0.89	79	79
Ephrin B1/EPHB1-2/NCK2	-0.043	0.13	-10000	0	-0.33	57	57
PI3K	-0.081	0.24	-10000	0	-0.65	83	83
mol:GDP	-0.072	0.16	-10000	0	-0.48	40	40
ITGA2B	-0.044	0.16	-10000	0	-0.5	63	63
endothelial cell proliferation	0.014	0.019	-10000	0	-0.31	2	2
FYN	-0.12	0.3	-10000	0	-0.89	79	79
MAP3K7	-0.09	0.24	-10000	0	-0.7	79	79
FGR	-0.13	0.3	-10000	0	-0.88	81	81
TIAM1	-0.044	0.16	-10000	0	-0.52	62	62
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
RGS3	0.011	0	-10000	0	-10000	0	0
cell adhesion	-0.099	0.24	-10000	0	-0.65	81	81
LYN	-0.12	0.3	-10000	0	-0.89	79	79
Ephrin B1/EPHB1-2/Src Family Kinases	-0.12	0.28	-10000	0	-0.83	79	79
Ephrin B1/EPHB1-2	-0.11	0.26	-10000	0	-0.76	79	79
SRC	-0.12	0.3	-10000	0	-0.88	79	79
ITGB3	-0.006	0.098	-10000	0	-0.54	19	19
EPHB1	-0.11	0.21	-10000	0	-0.49	138	138
EPHB4	0.011	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.014	0.019	-10000	0	-0.32	2	2
alphaIIb/beta3 Integrin	-0.036	0.13	-10000	0	-0.37	81	81
BLK	-0.15	0.31	-10000	0	-0.9	82	82
HCK	-0.13	0.3	-10000	0	-0.88	81	81
regulation of stress fiber formation	0.044	0.13	0.33	57	-10000	0	57
MAPK8	-0.072	0.22	-10000	0	-0.62	81	81
Ephrin B1/EPHB1-2/RGS3	-0.043	0.13	-10000	0	-0.33	53	53
endothelial cell migration	-0.074	0.21	-10000	0	-0.6	80	80
NCK2	0.01	0.024	-10000	0	-0.58	1	1
PTPN13	-0.095	0.25	-10000	0	-0.65	98	98
regulation of focal adhesion formation	0.044	0.13	0.33	57	-10000	0	57
chemotaxis	0.043	0.13	0.32	53	-10000	0	53
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
Rac1/GTP	-0.085	0.14	-10000	0	-0.47	34	34
angiogenesis	-0.11	0.26	-10000	0	-0.75	79	79
LCK	-0.13	0.31	-10000	0	-0.9	80	80

×

BMP receptor 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.13	0.2	-9999	-0.38	187	187
SMAD6-7/SMURF1	0.019	0.042	-9999	-0.38	6	6
NOG	-0.027	0.13	-9999	-0.48	43	43
SMAD9	-0.063	0.16	-9999	-0.51	58	58
SMAD4	0.004	0.064	-9999	-0.58	7	7
SMAD5	-0.044	0.14	-9999	-0.38	44	44
BMP7/USAG1	-0.17	0.24	-9999	-0.44	239	239
SMAD5/SKI	-0.036	0.13	-9999	-0.4	32	32
SMAD1	0.021	0.045	-9999	-0.47	3	3
BMP2	-0.003	0.087	-9999	-0.54	15	15
SMAD1/SMAD1/SMAD4	-0.007	0.046	-9999	-0.48	3	3
BMPR1A	0.01	0.024	-9999	-0.58	1	1
BMPR1B	-0.092	0.21	-9999	-0.51	117	117
BMPR1A-1B/BAMBI	-0.078	0.16	-9999	-0.32	173	173
AHSG	-0.043	0.15	-9999	-0.46	64	64
CER1	-0.005	0.062	-9999	-0.46	11	11
BMP2-4/CER1	-0.01	0.095	-9999	-0.31	50	50
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.049	0.14	-9999	-0.4	49	49
BMP2-4 (homodimer)	-0.01	0.1	-9999	-0.38	40	40
RGMB	-0.013	0.11	-9999	-0.46	31	31
BMP6/BMPR2/BMPR1A-1B	-0.044	0.14	-9999	-0.34	68	68
RGMA	-0.071	0.2	-9999	-0.54	89	89
SMURF1	0.011	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.049	0.13	-9999	-0.38	43	43
BMP2-4/USAG1	-0.071	0.17	-9999	-0.35	151	151
SMAD6/SMURF1/SMAD5	-0.036	0.13	-9999	-0.41	31	31
SOSTDC1	-0.1	0.23	-9999	-0.55	120	120
BMP7/BMPR2/BMPR1A-1B	-0.11	0.19	-9999	-0.38	149	149
SKI	0.011	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.009	0.1	-9999	-0.52	23	23
HFE2	0	0.038	-9999	-0.46	4	4
ZFYVE16	-0.005	0.096	-9999	-0.58	16	16
MAP3K7	0.011	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.018	0.12	-9999	-0.34	68	68
SMAD5/SMAD5/SMAD4	-0.039	0.13	-9999	-0.39	37	37
MAPK1	0.01	0.024	-9999	-0.58	1	1
TAK1/TAB family	-0.056	0.096	-9999	-0.37	27	27
BMP7 (homodimer)	-0.13	0.24	-9999	-0.54	153	153
NUP214	0.011	0	-9999	-10000	0	0
BMP6/FETUA	-0.037	0.12	-9999	-0.34	86	86
SMAD1/SKI	0.026	0.043	-9999	-0.44	3	3
SMAD6	0.007	0.05	-9999	-0.53	5	5
CTDSP2	0.011	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.033	0.12	-9999	-0.3	99	99
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.083	0.21	-9999	-0.54	102	102
BMPR2 (homodimer)	0.006	0.054	-9999	-0.58	5	5
GADD34/PP1CA	0.013	0.062	-9999	-0.35	16	16
BMPR1A-1B (homodimer)	-0.059	0.15	-9999	-0.36	118	118
CHRDL1	-0.16	0.25	-9999	-0.52	192	192
ENDOFIN/SMAD1	0.019	0.071	-9999	-0.47	6	6
SMAD6-7/SMURF1/SMAD1	-0.001	0.049	-9999	-0.54	3	3
SMAD6/SMURF1	0.011	0	-9999	-10000	0	0
BAMBI	-0.049	0.17	-9999	-0.52	67	67
SMURF2	0.007	0.05	-9999	-0.53	5	5
BMP2-4/CHRDL1	-0.1	0.18	-9999	-0.32	219	219
BMP2-4/GREM1	-0.058	0.16	-9999	-0.34	135	135
SMAD7	0.009	0.034	-9999	-0.58	2	2
SMAD8A/SMAD8A/SMAD4	-0.057	0.16	-9999	-0.48	60	60
SMAD1/SMAD6	0.026	0.043	-9999	-0.44	3	3
TAK1/SMAD6	0.017	0	-9999	-10000	0	0
BMP7	-0.13	0.24	-9999	-0.54	153	153
BMP6	-0.009	0.1	-9999	-0.52	23	23
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.039	0.12	-9999	-0.35	44	44
PPM1A	0.011	0	-9999	-10000	0	0
SMAD1/SMURF2	0.024	0.054	-9999	-0.48	4	4
SMAD7/SMURF1	0.015	0.025	-9999	-0.42	2	2
CTDSPL	0.011	0	-9999	-10000	0	0
PPP1CA	0.011	0	-9999	-10000	0	0
XIAP	0.01	0.024	-9999	-0.58	1	1
CTDSP1	0.01	0.024	-9999	-0.58	1	1
PPP1R15A	0.011	0.019	-9999	-0.46	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.08	0.18	-9999	-0.49	69	69
CHRD	-0.019	0.13	-9999	-0.55	32	32
BMPR2	0.006	0.054	-9999	-0.58	5	5
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.056	0.14	-9999	-0.42	43	43
BMP4	-0.012	0.11	-9999	-0.5	27	27
FST	-0.051	0.17	-9999	-0.53	69	69
BMP2-4/NOG	-0.023	0.12	-9999	-0.31	79	79
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.1	0.18	-9999	-0.35	149	149

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.015	0.024	-9999	-0.32	3	3
VLDLR	-0.041	0.16	-9999	-0.54	56	56
CRKL	0.011	0	-9999	-10000	0	0
LRPAP1	0.01	0.024	-9999	-0.58	1	1
FYN	0.005	0.06	-9999	-0.55	7	7
ITGA3	0.008	0.044	-9999	-0.52	4	4
RELN/VLDLR/Fyn	-0.078	0.17	-9999	-0.34	167	167
MAPK8IP1/MKK7/MAP3K11/JNK1	0.021	0.068	-9999	-0.33	14	14
AKT1	-0.07	0.14	-9999	-0.47	33	33
MAP2K7	0.01	0.024	-9999	-0.58	1	1
RAPGEF1	0.01	0.024	-9999	-0.58	1	1
DAB1	-0.079	0.2	-9999	-0.51	101	101
RELN/LRP8/DAB1	-0.09	0.17	-9999	-0.32	195	195
LRPAP1/LRP8	0.014	0.036	-9999	-0.42	4	4
RELN/LRP8/DAB1/Fyn	-0.082	0.16	-9999	-0.36	113	113
DAB1/alpha3/beta1 Integrin	-0.11	0.16	-9999	-0.5	48	48
long-term memory	-0.11	0.19	-9999	-0.52	59	59
DAB1/LIS1	-0.11	0.16	-9999	-0.51	46	46
DAB1/CRLK/C3G	-0.11	0.16	-9999	-0.5	47	47
PIK3CA	0.009	0.034	-9999	-0.58	2	2
DAB1/NCK2	-0.11	0.16	-9999	-0.52	47	47
ARHGEF2	0.011	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.019	0.11	-9999	-0.48	33	33
CDK5R1	0.009	0.033	-9999	-0.46	3	3
RELN	-0.094	0.21	-9999	-0.52	118	118
PIK3R1	0.008	0.042	-9999	-0.58	3	3
RELN/LRP8/Fyn	-0.049	0.14	-9999	-0.31	127	127
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.091	0.18	-9999	-0.37	129	129
MAPK8	0.01	0.024	-9999	-0.58	1	1
RELN/VLDLR/DAB1	-0.12	0.19	-9999	-0.34	229	229
ITGB1	0.011	0	-9999	-10000	0	0
MAP1B	-0.11	0.19	-9999	-0.4	138	138
RELN/LRP8	-0.045	0.14	-9999	-0.31	122	122
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.1	0.19	-9999	-0.37	147	147
PI3K	0.013	0.04	-9999	-0.42	5	5
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.014	0.032	-9999	-0.37	4	4
RAP1A	-0.075	0.16	-9999	-0.46	47	47
PAFAH1B1	0.011	0	-9999	-10000	0	0
MAPK8IP1	-0.01	0.11	-9999	-0.52	24	24
CRLK/C3G	0.016	0.018	-9999	-0.42	1	1
GRIN2B	-0.038	0.16	-9999	-0.56	51	51
NCK2	0.01	0.024	-9999	-0.58	1	1
neuron differentiation	-0.036	0.12	-9999	-0.38	27	27
neuron adhesion	-0.063	0.16	-9999	-0.47	36	36
LRP8	0.008	0.042	-9999	-0.58	3	3
GSK3B	-0.062	0.14	-9999	-0.45	34	34
RELN/VLDLR/DAB1/Fyn	-0.11	0.18	-9999	-0.38	144	144
MAP3K11	0.01	0.024	-9999	-0.58	1	1
RELN/VLDLR/DAB1/P13K	-0.08	0.15	-9999	-0.31	143	143
CDK5	0.011	0	-9999	-10000	0	0
MAPT	-0.064	0.18	-9999	-0.46	102	102
neuron migration	-0.064	0.16	-9999	-0.46	38	38
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.036	0.12	-9999	-0.38	27	27
RELN/VLDLR	-0.063	0.16	-9999	-0.35	96	96

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.23	0.46	-9999	-1.1	64	64
HDAC7	0.011	0.025	-9999	-0.58	1	1
HIF1A/ARNT/Cbp/p300/Src-1	-0.19	0.33	-9999	-0.9	53	53
SMAD4	0.005	0.064	-9999	-0.58	7	7
ID2	-0.23	0.46	-9999	-1.2	63	63
AP1	-0.014	0.11	-9999	-0.39	45	45
ABCG2	-0.26	0.48	-9999	-1.2	77	77
HIF1A	-0.029	0.11	-9999	-0.68	9	9
TFF3	-0.25	0.48	-9999	-1.2	80	80
GATA2	-0.018	0.13	-9999	-0.56	31	31
AKT1	-0.024	0.087	-9999	-0.72	1	1
response to hypoxia	-0.038	0.086	-9999	-0.23	12	12
MCL1	-0.23	0.46	-9999	-1.1	63	63
NDRG1	-0.23	0.46	-9999	-1.1	64	64
SERPINE1	-0.25	0.48	-9999	-1.2	74	74
FECH	-0.23	0.46	-9999	-1.1	64	64
FURIN	-0.23	0.46	-9999	-1.1	64	64
NCOA2	0.004	0.067	-9999	-0.56	8	8
EP300	-0.015	0.12	-9999	-0.35	24	24
HMOX1	-0.23	0.46	-9999	-1.2	63	63
BHLHE40	-0.23	0.46	-9999	-1.2	63	63
BHLHE41	-0.24	0.48	-9999	-1.2	69	69
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.036	0.11	-9999	-0.49	15	15
ENG	-0.004	0.12	-9999	-0.52	11	11
JUN	0.006	0.052	-9999	-0.56	5	5
RORA	-0.24	0.48	-9999	-1.2	71	71
ABCB1	-0.22	0.39	-9999	-1.1	91	91
TFRC	-0.23	0.46	-9999	-1.2	63	63
CXCR4	-0.24	0.48	-9999	-1.2	71	71
TF	-0.28	0.5	-9999	-1.1	87	87
CITED2	-0.23	0.46	-9999	-1.2	63	63
HIF1A/ARNT	-0.3	0.5	-9999	-1.3	74	74
LDHA	-0.036	0.078	-9999	-1.1	2	2
ETS1	-0.23	0.46	-9999	-1.2	63	63
PGK1	-0.23	0.46	-9999	-1.1	63	63
NOS2	-0.28	0.5	-9999	-1.2	84	84
ITGB2	-0.24	0.48	-9999	-1.2	72	72
ALDOA	-0.23	0.46	-9999	-1.2	63	63
Cbp/p300/CITED2	-0.22	0.47	-9999	-1.2	65	65
FOS	-0.026	0.14	-9999	-0.53	41	41
HK2	-0.23	0.46	-9999	-1.1	64	64
SP1	0.005	0.043	-9999	-0.58	1	1
GCK	-0.054	0.29	-9999	-1.2	24	24
HK1	-0.23	0.46	-9999	-1.1	63	63
NPM1	-0.23	0.46	-9999	-1.2	65	65
EGLN1	-0.23	0.46	-9999	-1.1	63	63
CREB1	0.016	0.035	-9999	-0.58	2	2
PGM1	-0.23	0.46	-9999	-1.1	64	64
SMAD3	0.006	0.062	-9999	-0.56	7	7
EDN1	-0.061	0.27	-9999	-1.1	25	25
IGFBP1	-0.28	0.5	-9999	-1.2	91	91
VEGFA	-0.12	0.34	-9999	-0.85	30	30
HIF1A/JAB1	-0.024	0.07	-9999	-0.49	10	10
CP	-0.29	0.51	-9999	-1.2	95	95
CXCL12	-0.24	0.47	-9999	-1.2	69	69
COPS5	0.011	0.019	-9999	-0.46	1	1
SMAD3/SMAD4	0.009	0.065	-9999	-0.41	14	14
BNIP3	-0.26	0.49	-9999	-1.2	79	79
EGLN3	-0.23	0.47	-9999	-1.2	67	67
CA9	-0.31	0.51	-9999	-1.1	111	111
TERT	-0.25	0.48	-9999	-1.1	79	79
ENO1	-0.23	0.46	-9999	-1.1	63	63
PFKL	-0.23	0.46	-9999	-1.2	63	63
NCOA1	0.011	0.024	-9999	-0.58	1	1
ADM	-0.23	0.46	-9999	-1.1	66	66
ARNT	-0.021	0.078	-9999	-0.64	1	1
HNF4A	0.004	0.066	-9999	-0.58	7	7
ADFP	-0.23	0.46	-9999	-1.1	70	70
SLC2A1	-0.12	0.34	-9999	-0.88	32	32
LEP	-0.24	0.47	-9999	-1.2	68	68
HIF1A/ARNT/Cbp/p300	-0.2	0.34	-9999	-0.92	55	55
EPO	-0.095	0.29	-9999	-1	12	12
CREBBP	-0.013	0.12	-9999	-0.35	19	19
HIF1A/ARNT/Cbp/p300/HDAC7	-0.19	0.33	-9999	-0.94	45	45
PFKFB3	-0.23	0.46	-9999	-1.1	64	64
NT5E	-0.24	0.48	-9999	-1.2	67	67

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.015	0.025	-10000	0	-0.42	2	2
Necdin/E2F1	0.008	0.059	-10000	0	-0.37	14	14
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.055	0.16	-10000	0	-0.36	105	105
NGF (dimer)/p75(NTR)/BEX1	-0.1	0.2	-10000	0	-0.38	179	179
NT-4/5 (dimer)/p75(NTR)	-0.066	0.16	-10000	0	-0.37	122	122
IKBKB	0.011	0.019	-10000	0	-0.46	1	1
AKT1	-0.041	0.14	-10000	0	-0.33	86	86
IKBKG	0.01	0.024	-10000	0	-0.58	1	1
BDNF	-0.021	0.13	-10000	0	-0.52	36	36
MGDIs/NGR/p75(NTR)/LINGO1	-0.062	0.16	-10000	0	-0.33	145	145
FURIN	0.01	0.031	-10000	0	-0.52	2	2
proBDNF (dimer)/p75(NTR)/Sortilin	-0.053	0.15	-10000	0	-0.33	129	129
LINGO1	-0.023	0.12	-10000	0	-0.47	43	43
Sortilin/TRAF6/NRIF	-0.008	0.05	-10000	0	-0.79	1	1
proBDNF (dimer)	-0.021	0.13	-10000	0	-0.52	36	36
NTRK1	-0.038	0.16	-10000	0	-0.53	53	53
RTN4R	-0.004	0.085	-10000	0	-0.48	18	18
neuron apoptosis	-0.06	0.17	-10000	0	-0.56	29	29
IRAK1	0.01	0.031	-10000	0	-0.52	2	2
SHC1	-0.059	0.16	-10000	0	-0.35	129	129
ARHGDIA	0.008	0.042	-10000	0	-0.58	3	3
RhoA/GTP	0.008	0.018	-10000	0	-0.43	1	1
Gamma Secretase	0.031	0.033	-10000	0	-0.29	6	6
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.051	0.16	-10000	0	-0.37	86	86
MAGEH1	0.003	0.071	-10000	0	-0.57	9	9
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.051	0.16	-10000	0	-0.38	85	85
Mammalian IAPs/DIABLO	0.006	0.1	-10000	0	-0.45	21	21
proNGF (dimer)	-0.032	0.14	-10000	0	-0.52	47	47
MAGED1	0.011	0	-10000	0	-10000	0	0
APP	0.01	0.024	-10000	0	-0.58	1	1
NT-4/5 (dimer)	-0.014	0.09	-10000	0	-0.46	23	23
ZNF274	0.001	0.076	-10000	0	-0.58	10	10
RhoA/GDP/RHOGDI	-0.045	0.14	-10000	0	-0.34	84	84
NGF	-0.032	0.14	-10000	0	-0.52	47	47
cell cycle arrest	-0.05	0.14	-10000	0	-0.34	80	80
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.024	0.11	-10000	0	-0.27	82	82
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.049	0.14	-10000	0	-0.31	123	123
NCSTN	0.011	0	-10000	0	-10000	0	0
mol:GTP	-0.078	0.18	-10000	0	-0.37	152	152
PSENEN	0.01	0.024	-10000	0	-0.58	1	1
mol:ceramide	-0.047	0.15	-10000	0	-0.37	80	80
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.012	0.098	-10000	0	-0.44	8	8
p75(NTR)/beta APP	-0.05	0.14	-10000	0	-0.36	105	105
BEX1	-0.059	0.18	-10000	0	-0.5	79	79
mol:GDP	-0.067	0.16	-10000	0	-0.36	129	129
NGF (dimer)	-0.11	0.18	-10000	0	-0.38	137	137
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.05	0.15	-10000	0	-0.39	62	62
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
RAC1/GTP	-0.05	0.14	-10000	0	-0.3	129	129
MYD88	0.011	0	-10000	0	-10000	0	0
CHUK	0.007	0.048	-10000	0	-0.58	4	4
NGF (dimer)/p75(NTR)/PKA	-0.079	0.18	-10000	0	-0.37	152	152
RHOB	0.009	0.039	-10000	0	-0.54	3	3
RHOA	0.01	0.024	-10000	0	-0.58	1	1
MAGE-G1/E2F1	0.015	0.026	-10000	0	-0.35	3	3
NT3 (dimer)	-0.02	0.13	-10000	0	-0.53	34	34
TP53	-0.061	0.16	-10000	0	-0.55	20	20
PRDM4	-0.048	0.15	-10000	0	-0.37	80	80
BDNF (dimer)	-0.18	0.22	-10000	0	-0.42	203	203
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
SORT1	0.01	0.024	-10000	0	-0.58	1	1
activation of caspase activity	-0.057	0.16	-10000	0	-0.35	105	105
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.047	0.15	-10000	0	-0.37	81	81
RHOC	0.011	0	-10000	0	-10000	0	0
XIAP	0.01	0.024	-10000	0	-0.58	1	1
MAPK10	-0.042	0.16	-10000	0	-0.51	30	30
DIABLO	0.011	0	-10000	0	-10000	0	0
SMPD2	-0.048	0.15	-10000	0	-0.37	80	80
APH1B	0.006	0.054	-10000	0	-0.58	5	5
APH1A	0.011	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.059	0.16	-10000	0	-0.35	129	129
PSEN1	0.011	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.014	0.036	-10000	0	-0.42	4	4
NT3 (dimer)/p75(NTR)	-0.07	0.17	-10000	0	-0.39	127	127
MAPK8	-0.026	0.14	-10000	0	-0.52	17	17
MAPK9	-0.026	0.14	-10000	0	-0.52	17	17
APAF1	0.008	0.042	-10000	0	-0.58	3	3
NTF3	-0.02	0.13	-10000	0	-0.53	34	34
NTF4	-0.014	0.09	-10000	0	-0.46	23	23
NDN	0.001	0.073	-10000	0	-0.52	11	11
RAC1/GDP	0.008	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.074	0.14	-10000	0	-0.47	33	33
p75 CTF/Sortilin/TRAF6/NRIF	0.021	0.061	-10000	0	-0.37	12	12
RhoA-B-C/GTP	-0.078	0.18	-10000	0	-0.37	152	152
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.038	0.14	-10000	0	-0.36	66	66
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.041	0.14	-10000	0	-0.37	60	60
PRKACB	-0.022	0.14	-10000	0	-0.57	34	34
proBDNF (dimer)/p75 ECD	-0.008	0.097	-10000	0	-0.38	38	38
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.016	0.12	-10000	0	-0.52	30	30
BIRC2	-0.002	0.087	-10000	0	-0.58	13	13
neuron projection morphogenesis	-0.063	0.16	0.19	19	-0.38	81	100
BAD	-0.027	0.14	-10000	0	-0.49	22	22
RIPK2	0.011	0	-10000	0	-10000	0	0
NGFR	-0.079	0.2	-10000	0	-0.51	104	104
CYCS	-0.047	0.15	-10000	0	-0.35	94	94
ADAM17	0.009	0.034	-10000	0	-0.58	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.046	0.15	-10000	0	-0.37	81	81
BCL2L11	-0.026	0.14	-10000	0	-0.49	22	22
BDNF (dimer)/p75(NTR)	-0.071	0.18	-10000	0	-0.39	129	129
PI3K	-0.048	0.15	-10000	0	-0.36	85	85
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.046	0.15	-10000	0	-0.37	80	80
NDNL2	0.011	0	-10000	0	-10000	0	0
YWHAE	0.011	0	-10000	0	-10000	0	0
PRKCI	0.008	0.042	-10000	0	-0.58	3	3
NGF (dimer)/p75(NTR)	-0.078	0.19	-10000	0	-0.42	129	129
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.046	0.15	-10000	0	-0.37	80	80
TRAF6	0.01	0.024	-10000	0	-0.58	1	1
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.031	-10000	0	-0.52	2	2
PLG	-0.036	0.15	-10000	0	-0.58	42	42
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.056	0.16	-10000	0	-0.37	95	95
SQSTM1	0.011	0	-10000	0	-10000	0	0
NGFRAP1	-0.021	0.14	-10000	0	-0.58	33	33
CASP3	-0.023	0.14	-10000	0	-0.45	22	22
E2F1	0.009	0.036	-10000	0	-0.5	3	3
CASP9	0.01	0.024	-10000	0	-0.58	1	1
IKK complex	-0.06	0.12	-10000	0	-0.42	39	39
NGF (dimer)/TRKA	-0.049	0.16	-10000	0	-0.41	90	90
MMP7	-0.14	0.24	-10000	0	-0.52	167	167
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.043	0.15	-10000	0	-0.35	87	87
MMP3	-0.13	0.24	-10000	0	-0.53	154	154
APAF-1/Caspase 9	-0.067	0.14	-10000	0	-0.57	25	25

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.039	0.17	-10000	0	-0.6	48	48
NFATC2	-0.092	0.26	-10000	0	-0.68	64	64
NFATC3	-0.019	0.076	-10000	0	-0.3	2	2
CD40LG	-0.28	0.42	-10000	0	-0.99	113	113
ITCH	0.028	0.084	-10000	0	-0.8	5	5
CBLB	0.028	0.08	-10000	0	-0.84	4	4
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.28	0.45	-10000	0	-1.2	96	96
JUNB	0.007	0.05	-10000	0	-0.53	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.008	0.059	-10000	0	-0.37	14	14
T cell anergy	0.004	0.1	-10000	0	-0.55	14	14
TLE4	-0.057	0.21	-10000	0	-0.7	37	37
Jun/NFAT1-c-4/p21SNFT	-0.18	0.37	-10000	0	-1	67	67
AP-1/NFAT1-c-4	-0.3	0.48	-10000	0	-1.1	107	107
IKZF1	-0.075	0.26	-10000	0	-0.78	52	52
T-helper 2 cell differentiation	-0.13	0.26	-10000	0	-0.88	41	41
AP-1/NFAT1	-0.093	0.21	-10000	0	-0.55	65	65
CALM1	0.018	0.033	-10000	0	-0.3	3	3
EGR2	-0.14	0.36	-10000	0	-1.1	46	46
EGR3	-0.15	0.38	-10000	0	-1.2	46	46
NFAT1/FOXP3	-0.093	0.27	-10000	0	-0.75	66	66
EGR1	-0.009	0.1	-10000	0	-0.5	24	24
JUN	-0.009	0.059	-10000	0	-0.58	5	5
EGR4	-0.055	0.17	-10000	0	-0.51	74	74
mol:Ca2+	0.007	0.035	-10000	0	-0.32	3	3
GBP3	-0.11	0.31	-10000	0	-0.8	86	86
FOSL1	-0.025	0.13	-10000	0	-0.51	41	41
NFAT1-c-4/MAF/IRF4	-0.18	0.38	-10000	0	-1	73	73
DGKA	-0.052	0.2	-10000	0	-0.65	35	35
CREM	0.01	0.019	-10000	0	-0.46	1	1
NFAT1-c-4/PPARG	-0.15	0.35	-10000	0	-1	57	57
CTLA4	-0.096	0.29	-10000	0	-0.79	69	69
NFAT1-c-4 (dimer)/EGR1	-0.16	0.36	-10000	0	-1	64	64
NFAT1-c-4 (dimer)/EGR4	-0.18	0.37	-10000	0	-1	68	68
FOS	-0.042	0.14	-10000	0	-0.55	41	41
IFNG	-0.23	0.4	-10000	0	-0.98	104	104
T cell activation	-0.11	0.2	-10000	0	-0.79	15	15
MAF	0.001	0.074	-10000	0	-0.54	11	11
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.11	0.3	0.94	45	-10000	0	45
TNF	-0.18	0.35	-10000	0	-0.94	72	72
FASLG	-0.24	0.51	-10000	0	-1.4	76	76
TBX21	-0.061	0.19	-10000	0	-0.56	71	71
BATF3	-0.006	0.094	-10000	0	-0.51	20	20
PRKCQ	-0.048	0.18	-10000	0	-0.58	57	57
PTPN1	-0.049	0.19	-10000	0	-0.63	32	32
NFAT1-c-4/ICER1	-0.15	0.35	-10000	0	-1	57	57
GATA3	-0.016	0.12	-10000	0	-0.52	31	31
T-helper 1 cell differentiation	-0.21	0.4	-10000	0	-0.95	104	104
IL2RA	-0.27	0.42	-10000	0	-1.1	97	97
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.05	0.19	-10000	0	-0.64	33	33
E2F1	0.014	0.036	-10000	0	-0.49	3	3
PPARG	0.004	0.064	-10000	0	-0.58	7	7
SLC3A2	-0.048	0.19	-10000	0	-0.63	31	31
IRF4	-0.076	0.2	-10000	0	-0.54	95	95
PTGS2	-0.3	0.44	-10000	0	-0.97	134	134
CSF2	-0.3	0.44	-10000	0	-0.98	131	131
JunB/Fra1/NFAT1-c-4	-0.16	0.34	-10000	0	-0.98	60	60
IL4	-0.13	0.27	-10000	0	-0.95	39	39
IL5	-0.26	0.4	-10000	0	-0.95	104	104
IL2	-0.11	0.2	-10000	0	-0.8	15	15
IL3	-0.064	0.1	-10000	0	-0.78	7	7
RNF128	0.025	0.091	-10000	0	-0.62	11	11
NFATC1	-0.12	0.3	-10000	0	-0.95	45	45
CDK4	0.081	0.18	0.6	24	-10000	0	24
PTPRK	-0.049	0.19	-10000	0	-0.64	31	31
IL8	-0.31	0.44	-10000	0	-0.98	137	137
POU2F1	0.002	0.072	-10000	0	-0.54	10	10

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.059	0.16	0.4	104	-10000	0	104
KIRREL	-0.032	0.14	-10000	0	-0.58	38	38
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.059	0.16	-10000	0	-0.4	104	104
PLCG1	0.01	0.024	-10000	0	-0.58	1	1
ARRB2	0.011	0	-10000	0	-10000	0	0
WASL	0.011	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.057	0.16	-10000	0	-0.38	88	88
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.023	0.11	-10000	0	-0.32	51	51
FYN	-0.042	0.13	-10000	0	-0.34	65	65
mol:Ca2+	-0.041	0.13	-10000	0	-0.36	61	61
mol:DAG	-0.041	0.14	-10000	0	-0.37	61	61
NPHS2	-0.021	0.092	-10000	0	-0.47	23	23
mol:IP3	-0.041	0.14	-10000	0	-0.37	61	61
regulation of endocytosis	-0.032	0.12	-10000	0	-0.32	61	61
Nephrin/NEPH1/podocin/Cholesterol	-0.047	0.13	-10000	0	-0.37	61	61
establishment of cell polarity	-0.059	0.16	-10000	0	-0.4	104	104
Nephrin/NEPH1/podocin/NCK1-2	-0.031	0.13	-10000	0	-0.33	62	62
Nephrin/NEPH1/beta Arrestin2	-0.032	0.12	-10000	0	-0.33	61	61
NPHS1	-0.057	0.17	-10000	0	-0.51	73	73
Nephrin/NEPH1/podocin	-0.041	0.13	-10000	0	-0.34	65	65
TJP1	0.01	0.024	-10000	0	-0.58	1	1
NCK1	0.009	0.034	-10000	0	-0.58	2	2
NCK2	0.01	0.024	-10000	0	-0.58	1	1
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.04	0.14	-10000	0	-0.37	61	61
CD2AP	-0.017	0.13	-10000	0	-0.58	29	29
Nephrin/NEPH1/podocin/GRB2	-0.04	0.13	-10000	0	-0.36	61	61
GRB2	0.011	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.051	0.15	-10000	0	-0.39	74	74
cytoskeleton organization	-0.027	0.13	-10000	0	-0.38	51	51
Nephrin/NEPH1	-0.04	0.12	-10000	0	-0.28	104	104
Nephrin/NEPH1/ZO-1	-0.039	0.14	-10000	0	-0.37	61	61

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.01	0.031	-10000	0	-0.52	2	2
LAT2	-0.064	0.17	-10000	0	-0.48	58	58
AP1	-0.11	0.2	-10000	0	-0.58	72	72
mol:PIP3	-0.082	0.22	-10000	0	-0.57	70	70
IKBKB	-0.034	0.13	0.15	13	-0.31	72	85
AKT1	-0.051	0.16	-10000	0	-0.45	47	47
IKBKG	-0.034	0.13	0.15	13	-0.31	73	86
MS4A2	-0.083	0.21	-10000	0	-0.54	101	101
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
MAP3K1	-0.054	0.18	-10000	0	-0.5	64	64
mol:Ca2+	-0.057	0.16	-10000	0	-0.41	70	70
LYN	0.009	0.006	-10000	0	-10000	0	0
CBLB	-0.061	0.17	-10000	0	-0.5	52	52
SHC1	0.011	0	-10000	0	-10000	0	0
RasGAP/p62DOK	0.011	0.055	-10000	0	-0.32	5	5
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	-0.017	0.12	-10000	0	-0.58	28	28
PLD2	-0.076	0.17	-10000	0	-0.39	99	99
PTPN13	-0.097	0.2	-10000	0	-0.58	56	56
PTPN11	0.003	0.056	-10000	0	-0.6	5	5
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.027	0.13	-10000	0	-0.36	42	42
SYK	0.008	0.02	-10000	0	-0.45	1	1
GRB2	0.011	0.001	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.12	0.2	-10000	0	-0.59	73	73
LAT	-0.07	0.18	-10000	0	-0.49	61	61
PAK2	-0.065	0.2	-10000	0	-0.55	67	67
NFATC2	-0.081	0.18	-10000	0	-0.65	46	46
HRAS	-0.077	0.22	-10000	0	-0.6	69	69
GAB2	0.009	0.034	-10000	0	-0.58	2	2
PLA2G1B	0.029	0.026	-10000	0	-10000	0	0
Fc epsilon R1	-0.12	0.2	-10000	0	-0.39	182	182
Antigen/IgE/Fc epsilon R1	-0.11	0.18	-10000	0	-0.37	168	168
mol:GDP	-0.089	0.24	-10000	0	-0.65	72	72
JUN	0.007	0.052	-10000	0	-0.56	5	5
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
FOS	-0.026	0.14	-10000	0	-0.53	41	41
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.069	0.17	-10000	0	-0.42	82	82
CHUK	-0.035	0.13	0.15	12	-0.31	73	85
KLRG1	-0.065	0.16	-10000	0	-0.47	54	54
VAV1	-0.078	0.2	-10000	0	-0.49	80	80
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.059	0.16	-10000	0	-0.48	50	50
negative regulation of mast cell degranulation	-0.069	0.17	-10000	0	-0.46	59	59
BTK	-0.092	0.26	-10000	0	-0.68	70	70
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.12	0.24	-10000	0	-0.65	75	75
GAB2/PI3K/SHP2	-0.09	0.15	-10000	0	-0.5	47	47
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.06	0.16	-10000	0	-0.47	48	48
RAF1	0.023	0.025	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.14	0.25	-10000	0	-0.48	164	164
FCER1G	-0.019	0.13	-10000	0	-0.54	34	34
FCER1A	-0.077	0.2	-10000	0	-0.56	90	90
Antigen/IgE/Fc epsilon R1/Fyn	-0.086	0.18	-10000	0	-0.38	137	137
MAPK3	0.029	0.025	-10000	0	-10000	0	0
MAPK1	0.029	0.026	-10000	0	-10000	0	0
NFKB1	0.01	0.024	-10000	0	-0.58	1	1
MAPK8	-0.006	0.073	-10000	0	-0.5	5	5
DUSP1	-0.007	0.092	-10000	0	-0.47	22	22
NF-kappa-B/RelA	-0.038	0.063	-10000	0	-0.22	27	27
actin cytoskeleton reorganization	-0.061	0.18	-10000	0	-0.59	38	38
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.098	0.19	-10000	0	-0.56	65	65
FER	-0.064	0.17	-10000	0	-0.48	55	55
RELA	0.011	0	-10000	0	-10000	0	0
ITK	-0.049	0.12	-10000	0	-0.45	44	44
SOS1	0.01	0.024	-10000	0	-0.58	1	1
PLCG1	-0.086	0.24	-10000	0	-0.64	72	72
cytokine secretion	-0.028	0.045	-10000	0	-10000	0	0
SPHK1	-0.08	0.19	-10000	0	-0.48	74	74
PTK2	-0.064	0.18	-10000	0	-0.62	38	38
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.12	0.21	-10000	0	-0.6	71	71
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.074	0.21	-10000	0	-0.55	70	70
MAP2K2	0.027	0.026	-10000	0	-10000	0	0
MAP2K1	0.026	0.03	-10000	0	-0.34	1	1
MAP2K7	0.01	0.024	-10000	0	-0.58	1	1
KLRG1/SHP2	-0.061	0.15	-10000	0	-0.45	51	51
MAP2K4	0.007	0.079	-10000	0	-0.94	4	4
Fc epsilon R1/FcgammaRIIB	-0.14	0.25	-10000	0	-0.49	162	162
mol:Choline	-0.075	0.17	-10000	0	-0.38	99	99
SHC/Grb2/SOS1	-0.047	0.16	-10000	0	-0.51	38	38
FYN	0.005	0.06	-10000	0	-0.55	7	7
DOK1	0.011	0	-10000	0	-10000	0	0
PXN	-0.053	0.17	-10000	0	-0.57	38	38
HCLS1	-0.066	0.18	-10000	0	-0.5	59	59
PRKCB	-0.06	0.18	-10000	0	-0.44	78	78
FCGR2B	-0.084	0.21	-10000	0	-0.53	104	104
IGHE	-0.003	0.007	-10000	0	-10000	0	0
KLRG1/SHIP	-0.07	0.17	-10000	0	-0.47	59	59
LCP2	-0.014	0.12	-10000	0	-0.55	27	27
PLA2G4A	-0.14	0.22	-10000	0	-0.45	140	140
RASA1	0.009	0.034	-10000	0	-0.58	2	2
mol:Phosphatidic acid	-0.075	0.17	-10000	0	-0.38	99	99
IKK complex	-0.015	0.1	0.15	13	-0.24	60	73
WIPF1	-0.001	0.081	-10000	0	-0.54	13	13

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.05	0.14	-10000	0	-0.37	94	94
TP53	-0.048	0.11	0.21	2	-0.36	55	57
Senescence	-0.047	0.11	0.21	2	-0.35	55	57
Apoptosis	-0.047	0.11	0.21	2	-0.35	55	57
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.03	0.084	0.26	39	-0.34	4	43
MDM4	0.01	0.031	-10000	0	-0.52	2	2

×

Calcium 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
NFATC1	-0.021	0.086	-9999	-0.34	33	33
NFATC2	-0.034	0.11	-9999	-0.38	50	50
NFATC3	-0.002	0.033	-9999	-10000	0	0
CD40LG	-0.18	0.32	-9999	-0.74	104	104
PTGS2	-0.2	0.33	-9999	-0.68	142	142
JUNB	0.007	0.05	-9999	-0.53	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.01	0.015	-9999	-10000	0	0
CaM/Ca2+	-0.009	0.015	-9999	-10000	0	0
CALM1	0.006	0.011	-9999	-10000	0	0
JUN	0.001	0.053	-9999	-0.56	5	5
mol:Ca2+	-0.009	0.013	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.004	0.007	-9999	-10000	0	0
FOSL1	-0.025	0.13	-9999	-0.51	41	41
CREM	0.01	0.019	-9999	-0.46	1	1
Jun/NFAT1-c-4/p21SNFT	-0.1	0.2	-9999	-0.52	72	72
FOS	-0.032	0.14	-9999	-0.54	41	41
IFNG	-0.19	0.32	-9999	-0.7	130	130
AP-1/NFAT1-c-4	-0.2	0.35	-9999	-0.75	125	125
FASLG	-0.18	0.32	-9999	-0.72	120	120
NFAT1-c-4/ICER1	-0.062	0.14	-9999	-0.4	55	55
IL2RA	-0.18	0.32	-9999	-0.76	103	103
FKBP12/FK506	0.008	0	-9999	-10000	0	0
CSF2	-0.2	0.34	-9999	-0.7	143	143
JunB/Fra1/NFAT1-c-4	-0.076	0.15	-9999	-0.41	67	67
IL4	-0.16	0.28	-9999	-0.67	92	92
IL2	-0.007	0.024	-9999	-10000	0	0
IL3	-0.03	0.093	-9999	-0.84	7	7
FKBP1A	0.011	0	-9999	-10000	0	0
BATF3	-0.006	0.094	-9999	-0.51	20	20
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.002	0.072	-9999	-0.54	10	10

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.051	0.15	-9999	-0.34	117	117
EPHB2	0	0.079	-9999	-0.55	12	12
Syndecan-2/TACI	-0.037	0.13	-9999	-0.32	97	97
LAMA1	-0.055	0.18	-9999	-0.54	72	72
Syndecan-2/alpha2 ITGB1	0.004	0.091	-9999	-0.31	33	33
HRAS	0.008	0.041	-9999	-0.49	4	4
Syndecan-2/CASK	0	0.063	-9999	-0.34	20	20
ITGA5	-0.005	0.09	-9999	-0.49	20	20
BAX	0.019	0.075	-9999	-1.1	1	1
EPB41	0.007	0.048	-9999	-0.58	4	4
positive regulation of cell-cell adhesion	0.002	0.075	-9999	-0.32	29	29
LAMA3	-0.016	0.12	-9999	-0.51	32	32
EZR	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.003	0.087	-9999	-0.51	17	17
Syndecan-2/MMP2	-0.018	0.13	-9999	-0.39	56	56
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.013	0.044	-9999	-0.42	6	6
dendrite morphogenesis	0.002	0.081	-9999	-0.34	31	31
Syndecan-2/GM-CSF	-0.058	0.14	-9999	-0.32	138	138
determination of left/right symmetry	0.002	0.075	-9999	-0.4	20	20
Syndecan-2/PKC delta	0.009	0.064	-9999	-0.34	19	19
GNB2L1	0.011	0.019	-9999	-0.46	1	1
MAPK3	-0.046	0.13	-9999	-0.32	78	78
MAPK1	-0.046	0.13	-9999	-0.28	139	139
Syndecan-2/RACK1	0.013	0.062	-9999	-0.31	19	19
NF1	0.008	0.042	-9999	-0.58	3	3
FGFR/FGF/Syndecan-2	0.002	0.075	-9999	-0.4	20	20
ITGA2	0.005	0.059	-9999	-0.58	6	6
MAPK8	0.015	0.068	-9999	-0.34	21	21
Syndecan-2/alpha2/beta1 Integrin	-0.017	0.12	-9999	-0.3	67	67
Syndecan-2/Kininogen	-0.067	0.15	-9999	-0.32	152	152
ITGB1	0.011	0	-9999	-10000	0	0
SRC	0.017	0.064	-9999	-0.31	18	18
Syndecan-2/CASK/Protein 4.1	0.006	0.064	-9999	-0.31	23	23
extracellular matrix organization	0	0.092	-9999	-0.38	30	30
actin cytoskeleton reorganization	-0.05	0.15	-9999	-0.34	117	117
Syndecan-2/Caveolin-2/Ras	0.006	0.085	-9999	-0.31	37	37
Syndecan-2/Laminin alpha3	-0.008	0.095	-9999	-0.31	51	51
Syndecan-2/RasGAP	0.017	0.064	-9999	-0.3	20	20
alpha5/beta1 Integrin	0.005	0.065	-9999	-0.34	20	20
PRKCD	0.011	0	-9999	-10000	0	0
Syndecan-2 dimer	0.002	0.081	-9999	-0.34	31	31
GO:0007205	0.003	0.006	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.023	0.066	-9999	-0.3	20	20
RHOA	0.01	0.024	-9999	-0.58	1	1
SDCBP	0	0.08	-9999	-0.58	11	11
TNFRSF13B	-0.062	0.18	-9999	-0.52	80	80
RASA1	0.009	0.034	-9999	-0.58	2	2
alpha2/beta1 Integrin	0.013	0.044	-9999	-0.42	6	6
Syndecan-2/Synbindin	0.009	0.064	-9999	-0.34	19	19
TGFB1	-0.003	0.088	-9999	-0.55	15	15
CASP3	0.014	0.061	-9999	-0.3	21	21
FN1	-0.086	0.21	-9999	-0.52	109	109
Syndecan-2/IL8	-0.064	0.16	-9999	-0.33	144	144
SDC2	0.002	0.075	-9999	-0.4	20	20
KNG1	-0.11	0.22	-9999	-0.52	136	136
Syndecan-2/Neurofibromin	0.007	0.069	-9999	-0.34	22	22
TRAPPC4	0.011	0	-9999	-10000	0	0
CSF2	-0.097	0.22	-9999	-0.52	121	121
Syndecan-2/TGFB1	0	0.092	-9999	-0.38	30	30
Syndecan-2/Syntenin/PI-4-5-P2	0.002	0.075	-9999	-0.32	29	29
Syndecan-2/Ezrin	0.015	0.06	-9999	-0.3	20	20
PRKACA	0.014	0.063	-9999	-0.31	19	19
angiogenesis	-0.063	0.16	-9999	-0.33	144	144
MMP2	-0.034	0.15	-9999	-0.53	50	50
IL8	-0.11	0.22	-9999	-0.52	133	133
calcineurin-NFAT signaling pathway	-0.036	0.13	-9999	-0.32	97	97

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.004	0.09	-10000	0	-0.54	16	16
GNB1/GNG2	-0.053	0.069	-10000	0	-0.2	81	81
AKT1	-0.022	0.092	-10000	0	-0.21	71	71
EGF	-0.18	0.25	-10000	0	-0.51	216	216
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.033	0.12	-10000	0	-0.41	26	26
mol:Ca2+	-0.046	0.13	-10000	0	-0.3	84	84
LYN	-0.017	0.094	-10000	0	-0.42	10	10
RhoA/GTP	-0.03	0.046	-10000	0	-0.14	39	39
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.051	0.14	-10000	0	-0.35	79	79
GNG2	0.004	0.063	-10000	0	-0.53	8	8
ARRB2	0.011	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.006	0.11	-10000	0	-0.47	23	23
G beta5/gamma2	-0.067	0.092	-10000	0	-0.26	81	81
PRKCH	-0.052	0.15	-10000	0	-0.35	81	81
DNM1	-0.006	0.093	-10000	0	-0.5	20	20
TXA2/TP beta/beta Arrestin3	-0.015	0.036	-10000	0	-0.25	7	7
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.12	0.23	-10000	0	-0.5	149	149
G12 family/GTP	-0.073	0.11	-10000	0	-0.3	82	82
ADRBK1	0.01	0.031	-10000	0	-0.52	2	2
ADRBK2	-0.001	0.085	-10000	0	-0.57	13	13
RhoA/GTP/ROCK1	0.006	0.056	-10000	0	-0.39	11	11
mol:GDP	0.044	0.11	0.32	43	-10000	0	43
mol:NADP	-0.007	0.098	-10000	0	-0.53	20	20
RAB11A	0.011	0	-10000	0	-10000	0	0
PRKG1	-0.024	0.14	-10000	0	-0.56	37	37
mol:IP3	-0.061	0.16	-10000	0	-0.38	84	84
cell morphogenesis	0.006	0.056	-10000	0	-0.39	11	11
PLCB2	-0.086	0.21	-10000	0	-0.52	84	84
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.073	0.14	-10000	0	-0.41	46	46
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.029	0.12	-10000	0	-0.44	21	21
RHOA	0.01	0.024	-10000	0	-0.58	1	1
PTGIR	-0.007	0.096	-10000	0	-0.5	21	21
PRKCB1	-0.058	0.15	-10000	0	-0.37	84	84
GNAQ	0.005	0.059	-10000	0	-0.58	6	6
mol:L-citrulline	-0.007	0.098	-10000	0	-0.53	20	20
TXA2/TXA2-R family	-0.089	0.21	-10000	0	-0.53	85	85
LCK	-0.035	0.12	-10000	0	-0.43	22	22
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.049	0.096	-10000	0	-0.5	9	9
TXA2-R family/G12 family/GDP/G beta/gamma	0.006	0.04	-10000	0	-0.3	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.046	0.094	-10000	0	-0.49	9	9
MAPK14	-0.028	0.1	-10000	0	-0.23	72	72
TGM2/GTP	-0.074	0.18	-10000	0	-0.45	82	82
MAPK11	-0.032	0.11	-10000	0	-0.24	77	77
ARHGEF1	-0.023	0.08	-10000	0	-0.18	59	59
GNAI2	0.011	0	-10000	0	-10000	0	0
JNK cascade	-0.062	0.16	-10000	0	-0.39	85	85
RAB11/GDP	0.012	0.001	-10000	0	-10000	0	0
ICAM1	-0.04	0.12	-10000	0	-0.29	78	78
cAMP biosynthetic process	-0.064	0.15	-10000	0	-0.37	83	83
Gq family/GTP/EBP50	0.004	0.079	-10000	0	-0.28	34	34
actin cytoskeleton reorganization	0.006	0.056	-10000	0	-0.39	11	11
SRC	-0.017	0.095	-10000	0	-0.42	11	11
GNB5	0.007	0.048	-10000	0	-0.58	4	4
GNB1	0.011	0	-10000	0	-10000	0	0
EGF/EGFR	-0.062	0.12	-10000	0	-0.33	58	58
VCAM1	-0.049	0.14	-10000	0	-0.32	86	86
TP beta/Gq family/GDP/G beta5/gamma2	-0.006	0.11	-10000	0	-0.47	23	23
platelet activation	-0.04	0.14	-10000	0	-0.3	84	84
PGI2/IP	-0.005	0.069	-10000	0	-0.36	21	21
PRKACA	-0.047	0.12	-10000	0	-0.31	65	65
Gq family/GDP/G beta5/gamma2	-0.01	0.1	-10000	0	-0.45	24	24
TXA2/TP beta/beta Arrestin2	-0.016	0.065	-10000	0	-0.49	9	9
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.04	0.12	-10000	0	-0.54	10	10
mol:DAG	-0.065	0.17	-10000	0	-0.42	82	82
EGFR	0.004	0.063	-10000	0	-0.53	8	8
TXA2/TP alpha	-0.088	0.2	-10000	0	-0.51	83	83
Gq family/GTP	-0.011	0.079	-10000	0	-0.28	34	34
YES1	-0.02	0.1	-10000	0	-0.44	12	12
GNAI2/GTP	-0.049	0.092	-10000	0	-0.47	11	11
PGD2/DP	-0.085	0.16	-10000	0	-0.36	149	149
SLC9A3R1	0.011	0	-10000	0	-10000	0	0
FYN	-0.02	0.097	-10000	0	-0.42	11	11
mol:NO	-0.007	0.098	-10000	0	-0.53	20	20
GNA15	-0.008	0.1	-10000	0	-0.54	21	21
PGK/cGMP	-0.018	0.11	-10000	0	-0.34	56	56
RhoA/GDP	0.011	0.024	-10000	0	-0.57	1	1
TP alpha/TGM2/GDP/G beta/gamma	-0.029	0.12	-10000	0	-0.49	15	15
NOS3	-0.007	0.098	-10000	0	-0.53	20	20
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCA	-0.051	0.14	-10000	0	-0.34	80	80
PRKCB	-0.064	0.17	-10000	0	-0.39	93	93
PRKCE	-0.048	0.14	-10000	0	-0.34	80	80
PRKCD	-0.054	0.15	-10000	0	-0.37	80	80
PRKCG	-0.088	0.18	-10000	0	-0.41	106	106
muscle contraction	-0.082	0.2	-10000	0	-0.5	85	85
PRKCZ	-0.051	0.14	-10000	0	-0.35	82	82
ARR3	-0.001	0.042	-10000	0	-0.46	5	5
TXA2/TP beta	-0.036	0.12	-10000	0	-0.52	12	12
PRKCQ	-0.066	0.16	-10000	0	-0.37	94	94
MAPKKK cascade	-0.077	0.19	-10000	0	-0.47	86	86
SELE	-0.062	0.16	-10000	0	-0.37	98	98
TP beta/GNAI2/GDP/G beta/gamma	-0.022	0.11	-10000	0	-0.52	10	10
ROCK1	0	0.08	-10000	0	-0.58	11	11
GNA14	-0.007	0.1	-10000	0	-0.56	19	19
chemotaxis	-0.098	0.23	-10000	0	-0.6	83	83
GNA12	0.011	0	-10000	0	-10000	0	0
GNA13	0.009	0.034	-10000	0	-0.58	2	2
GNA11	0.007	0.05	-10000	0	-0.53	5	5
Rac1/GTP	0.007	0.003	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.065	0.16	-9999	-0.44	31	31
NF kappa B1 p50/RelA/I kappa B alpha	-0.039	0.15	-9999	-0.48	21	21
alphaV/beta3 Integrin/Osteopontin/Src	-0.11	0.19	-9999	-0.36	204	204
AP1	-0.074	0.2	-9999	-0.56	53	53
ILK	-0.074	0.16	-9999	-0.45	29	29
bone resorption	-0.051	0.16	-9999	-0.54	20	20
PTK2B	0.009	0.034	-9999	-0.58	2	2
PYK2/p130Cas	-0.059	0.15	-9999	-0.5	20	20
ITGAV	0.003	0.079	-9999	-0.57	11	11
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.006	0.072	-9999	-0.45	14	14
alphaV/beta3 Integrin/Osteopontin	-0.09	0.18	-9999	-0.37	119	119
MAP3K1	-0.079	0.17	-9999	-0.35	117	117
JUN	0.007	0.052	-9999	-0.56	5	5
MAPK3	-0.062	0.16	-9999	-0.48	24	24
MAPK1	-0.062	0.16	-9999	-0.42	37	37
Rac1/GDP	0.008	0	-9999	-10000	0	0
NFKB1	0.01	0.024	-9999	-0.58	1	1
MAPK8	-0.068	0.17	-9999	-0.46	38	38
ITGB3	-0.004	0.099	-9999	-0.55	19	19
NFKBIA	-0.053	0.16	-9999	-0.47	27	27
FOS	-0.026	0.14	-9999	-0.53	41	41
CD44	0.007	0.048	-9999	-0.58	4	4
CHUK	0.007	0.048	-9999	-0.58	4	4
PLAU	-0.05	0.19	-9999	-0.71	21	21
NF kappa B1 p50/RelA	-0.077	0.12	-9999	-0.51	20	20
BCAR1	0.008	0.044	-9999	-0.52	4	4
RELA	0.011	0	-9999	-10000	0	0
alphaV beta3 Integrin	0.001	0.095	-9999	-0.41	29	29
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.076	0.16	-9999	-0.34	112	112
VAV3	-0.1	0.19	-9999	-0.53	47	47
MAP3K14	-0.074	0.16	-9999	-0.34	119	119
ROCK2	0	0.08	-9999	-0.58	11	11
SPP1	-0.16	0.25	-9999	-0.51	194	194
RAC1	0.011	0	-9999	-10000	0	0
Rac1/GTP	-0.092	0.18	-9999	-0.51	42	42
MMP2	-0.075	0.21	-9999	-0.6	55	55

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.021	0.074	0.33	8	-10000	0	8
SMARCC2	0.012	0.006	-10000	0	-10000	0	0
SMARCC1	0.012	0.006	-10000	0	-10000	0	0
TBX21	-0.11	0.27	-10000	0	-0.7	84	84
SUMO2	0.01	0.025	-10000	0	-0.58	1	1
STAT1 (dimer)	0.013	0.052	-10000	0	-0.49	6	6
FKBP4	0.009	0.033	-10000	0	-0.46	3	3
FKBP5	0.009	0.039	-10000	0	-0.54	3	3
GR alpha/HSP90/FKBP51/HSP90	0.075	0.11	0.3	47	-0.39	8	55
PRL	-0.064	0.14	-10000	0	-0.68	6	6
cortisol/GR alpha (dimer)/TIF2	0.18	0.23	0.54	109	-0.5	5	114
RELA	-0.036	0.093	-10000	0	-0.3	19	19
FGG	0.12	0.2	0.51	50	-0.46	10	60
GR beta/TIF2	0.074	0.13	0.32	46	-0.46	12	58
IFNG	-0.27	0.37	-10000	0	-0.98	92	92
apoptosis	0.007	0.16	0.48	21	-0.57	7	28
CREB1	0.009	0.041	-10000	0	-0.58	2	2
histone acetylation	-0.031	0.12	0.33	1	-0.35	41	42
BGLAP	-0.051	0.14	-10000	0	-0.55	17	17
GR/PKAc	0.055	0.13	0.3	27	-0.41	11	38
NF kappa B1 p50/RelA	-0.068	0.18	-10000	0	-0.48	49	49
SMARCD1	0.011	0.025	-10000	0	-0.58	1	1
MDM2	0.072	0.087	0.26	56	-0.28	3	59
GATA3	-0.016	0.12	-10000	0	-0.52	31	31
AKT1	0.003	0.024	-10000	0	-0.59	1	1
CSF2	-0.18	0.38	-10000	0	-1.2	68	68
GSK3B	0.009	0.035	-10000	0	-0.58	2	2
NR1I3	0.021	0.18	0.47	18	-0.82	13	31
CSN2	0.11	0.15	0.42	41	-0.39	2	43
BRG1/BAF155/BAF170/BAF60A	0.032	0.029	-10000	0	-0.31	2	2
NFATC1	-0.016	0.12	-10000	0	-0.5	33	33
POU2F1	0.001	0.075	-10000	0	-0.55	10	10
CDKN1A	-0.018	0.16	-10000	0	-1.5	3	3
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.007	-10000	0	-10000	0	0
SFN	0.005	0.056	-10000	0	-0.47	8	8
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.076	0.11	0.29	41	-0.43	6	47
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.019	0.17	0.45	18	-0.79	11	29
JUN	-0.16	0.19	-10000	0	-0.48	92	92
IL4	-0.076	0.14	-10000	0	-0.53	15	15
CDK5R1	0.009	0.033	-10000	0	-0.46	3	3
PRKACA	0.011	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.13	0.2	0.22	32	-0.48	86	118
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.079	0.11	0.3	36	-0.42	5	41
cortisol/GR alpha (monomer)	0.21	0.28	0.65	113	-0.46	4	117
NCOA2	0.004	0.067	-10000	0	-0.56	8	8
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.078	0.15	-10000	0	-0.58	41	41
AP-1/NFAT1-c-4	-0.27	0.3	-10000	0	-0.7	139	139
AFP	-0.12	0.17	-10000	0	-0.62	26	26
SUV420H1	0.01	0.024	-10000	0	-0.58	1	1
IRF1	0.12	0.14	0.44	36	-0.58	1	37
TP53	-0.031	0.18	-10000	0	-0.57	59	59
PPP5C	0.011	0	-10000	0	-10000	0	0
KRT17	-0.34	0.44	-10000	0	-0.99	150	150
KRT14	-0.11	0.2	-10000	0	-0.61	45	45
TBP	0.017	0.026	-10000	0	-0.37	2	2
CREBBP	0.034	0.054	0.26	4	-0.24	3	7
HDAC1	0.011	0.009	-10000	0	-10000	0	0
HDAC2	0.022	0.027	-10000	0	-10000	0	0
AP-1	-0.27	0.31	-10000	0	-0.7	139	139
MAPK14	0.011	0.006	-10000	0	-10000	0	0
MAPK10	-0.032	0.15	-10000	0	-0.55	46	46
MAPK11	-0.003	0.082	-10000	0	-0.48	17	17
KRT5	-0.31	0.41	-10000	0	-0.86	158	158
interleukin-1 receptor activity	0.011	0.027	-10000	0	-10000	0	0
NCOA1	0.013	0.024	-10000	0	-0.58	1	1
STAT1	0.013	0.052	-10000	0	-0.49	6	6
CGA	-0.063	0.13	-10000	0	-0.46	27	27
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.12	0.2	0.48	95	-0.52	5	100
MAPK3	0.01	0.025	-10000	0	-0.58	1	1
MAPK1	0.01	0.025	-10000	0	-0.58	1	1
ICAM1	-0.14	0.23	-10000	0	-0.62	67	67
NFKB1	-0.037	0.098	-10000	0	-0.37	12	12
MAPK8	-0.12	0.16	-10000	0	-0.43	76	76
MAPK9	0.011	0.006	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0	0.16	0.48	21	-0.6	7	28
BAX	-0.013	0.13	-10000	0	-0.75	3	3
POMC	-0.14	0.32	-10000	0	-1.1	40	40
EP300	0.031	0.073	0.26	5	-0.41	7	12
cortisol/GR alpha (dimer)/p53	0.15	0.26	0.56	99	-0.42	12	111
proteasomal ubiquitin-dependent protein catabolic process	0.049	0.068	0.23	22	-0.24	3	25
SGK1	0.064	0.13	0.42	1	-1.4	3	4
IL13	-0.18	0.22	-10000	0	-0.74	38	38
IL6	-0.24	0.4	-10000	0	-0.88	134	134
PRKACG	0.001	0.033	-10000	0	-0.46	3	3
IL5	-0.15	0.18	-10000	0	-0.65	29	29
IL2	-0.2	0.23	-10000	0	-0.68	57	57
CDK5	0.011	0.003	-10000	0	-10000	0	0
PRKACB	-0.022	0.14	-10000	0	-0.57	34	34
HSP90AA1	0.01	0.024	-10000	0	-0.58	1	1
IL8	-0.24	0.41	-10000	0	-0.9	132	132
CDK5R1/CDK5	0.015	0.025	-10000	0	-0.32	3	3
NF kappa B1 p50/RelA/PKAc	-0.05	0.16	-10000	0	-0.53	31	31
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.18	0.21	0.52	109	-0.41	1	110
SMARCA4	0.011	0.025	-10000	0	-0.58	1	1
chromatin remodeling	0.12	0.14	0.37	75	-0.41	4	79
NF kappa B1 p50/RelA/Cbp	-0.016	0.16	0.31	2	-0.5	28	30
JUN (dimer)	-0.16	0.19	-10000	0	-0.47	92	92
YWHAH	0.011	0	-10000	0	-10000	0	0
VIPR1	-0.078	0.21	-10000	0	-0.72	43	43
NR3C1	0.12	0.18	0.44	78	-0.46	11	89
NR4A1	-0.033	0.15	-10000	0	-0.47	56	56
TIF2/SUV420H1	0.01	0.052	-10000	0	-0.41	9	9
MAPKKK cascade	0.007	0.16	0.48	21	-0.57	7	28
cortisol/GR alpha (dimer)/Src-1	0.19	0.23	0.55	109	-0.44	3	112
PBX1	-0.005	0.092	-10000	0	-0.56	15	15
POU1F1	-0.001	0.037	-10000	0	-0.51	2	2
SELE	-0.23	0.39	-10000	0	-1	94	94
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.12	0.14	0.37	75	-0.41	4	79
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.18	0.21	0.52	109	-0.41	1	110
mol:cortisol	0.12	0.16	0.37	121	-10000	0	121
MMP1	-0.27	0.45	-10000	0	-1	136	136

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.026	0.051	-9999	-0.56	2	2
Crk/p130 Cas/Paxillin	-0.06	0.11	-9999	-0.39	28	28
JUN	-0.03	0.12	-9999	-0.44	24	24
HRAS	0.008	0.041	-9999	-0.49	4	4
RET51/GFRalpha1/GDNF/GRB10	-0.074	0.17	-9999	-0.41	87	87
RAP1A	0.01	0.024	-9999	-0.58	1	1
FRS2	0.009	0.034	-9999	-0.58	2	2
RAP1A/GDP	0.008	0.018	-9999	-0.43	1	1
RET51/GFRalpha1/GDNF/DOK1	-0.072	0.17	-9999	-0.4	86	86
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.006	0.054	-9999	-0.58	5	5
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.011	0.019	-9999	-0.46	1	1
RET9/GFRalpha1/GDNF/Enigma	-0.03	0.12	-9999	-0.29	96	96
RHOA	0.01	0.024	-9999	-0.58	1	1
RAP1A/GTP	-0.082	0.14	-9999	-0.36	87	87
GRB7	0.002	0.066	-9999	-0.46	12	12
RET51/GFRalpha1/GDNF	-0.072	0.17	-9999	-0.4	86	86
MAPKKK cascade	-0.074	0.13	-9999	-0.48	32	32
BCAR1	0.008	0.044	-9999	-0.52	4	4
RET9/GFRalpha1/GDNF/IRS1	-0.032	0.12	-9999	-0.3	98	98
lamellipodium assembly	-0.055	0.098	-9999	-0.3	61	61
RET51/GFRalpha1/GDNF/SHC	-0.072	0.17	-9999	-0.4	86	86
PIK3CA	0.009	0.034	-9999	-0.58	2	2
RET9/GFRalpha1/GDNF/SHC	-0.027	0.11	-9999	-0.29	91	91
RET9/GFRalpha1/GDNF/Shank3	-0.03	0.12	-9999	-0.3	93	93
MAPK3	-0.054	0.15	-9999	-0.49	28	28
DOK1	0.011	0	-9999	-10000	0	0
DOK6	-0.03	0.15	-9999	-0.55	44	44
PXN	0.011	0	-9999	-10000	0	0
neurite development	-0.049	0.15	-9999	-0.46	37	37
DOK5	-0.049	0.17	-9999	-0.54	65	65
GFRA1	-0.069	0.19	-9999	-0.53	89	89
MAPK8	-0.035	0.12	-9999	-0.45	21	21
HRAS/GTP	-0.082	0.14	-9999	-0.5	33	33
tube development	-0.023	0.11	-9999	-0.32	56	56
MAPK1	-0.054	0.15	-9999	-0.48	29	29
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.014	0.093	-9999	-0.27	59	59
Rac1/GDP	0.008	0	-9999	-10000	0	0
SRC	0.01	0.024	-9999	-0.58	1	1
PDLIM7	0.006	0.052	-9999	-0.47	7	7
RET51/GFRalpha1/GDNF/Dok6	-0.084	0.19	-9999	-0.41	112	112
SHC1	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.073	0.17	-9999	-0.4	86	86
RET51/GFRalpha1/GDNF/Dok5	-0.11	0.2	-9999	-0.43	123	123
PRKCA	0.01	0.031	-9999	-0.52	2	2
HRAS/GDP	0.006	0.03	-9999	-0.35	4	4
CREB1	-0.028	0.12	-9999	-0.35	54	54
PIK3R1	0.008	0.042	-9999	-0.58	3	3
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.01	0.086	-9999	-0.26	53	53
RET51/GFRalpha1/GDNF/Grb7	-0.077	0.17	-9999	-0.4	87	87
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.084	0.2	-9999	-0.5	111	111
DOK4	0.01	0.024	-9999	-0.58	1	1
JNK cascade	-0.029	0.12	-9999	-0.43	24	24
RET9/GFRalpha1/GDNF/FRS2	-0.028	0.11	-9999	-0.29	93	93
SHANK3	0.006	0.055	-9999	-0.54	6	6
RASA1	0.009	0.034	-9999	-0.58	2	2
NCK1	0.009	0.034	-9999	-0.58	2	2
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.011	0.087	-9999	-0.26	54	54
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.045	0.13	-9999	-0.31	92	92
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.043	0.13	-9999	-0.4	31	31
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.045	0.14	-9999	-0.34	80	80
PI3K	-0.046	0.17	-9999	-0.45	61	61
SOS1	0.01	0.024	-9999	-0.58	1	1
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.022	0.11	-9999	-0.32	56	56
GRB10	0.007	0.048	-9999	-0.58	4	4
activation of MAPKK activity	-0.035	0.12	-9999	-0.41	23	23
RET51/GFRalpha1/GDNF/FRS2	-0.073	0.17	-9999	-0.4	88	88
GAB1	0.011	0	-9999	-10000	0	0
IRS1	0.002	0.072	-9999	-0.58	9	9
IRS2	0.003	0.068	-9999	-0.54	9	9
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.045	0.14	-9999	-0.33	86	86
RET51/GFRalpha1/GDNF/PKC alpha	-0.073	0.17	-9999	-0.4	86	86
GRB2	0.011	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GDNF	0.006	0.036	-9999	-0.5	3	3
RAC1	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.077	0.18	-9999	-0.41	90	90
Rac1/GTP	-0.064	0.12	-9999	-0.36	61	61
RET9/GFRalpha1/GDNF	-0.038	0.12	-9999	-0.32	91	91
GFRalpha1/GDNF	-0.046	0.14	-9999	-0.38	91	91

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.011	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.028	0.12	-10000	0	-0.43	22	22
NT3 (dimer)/TRKC	-0.045	0.15	-10000	0	-0.39	89	89
NT3 (dimer)/TRKB	-0.17	0.21	-10000	0	-0.35	299	299
SHC/Grb2/SOS1/GAB1/PI3K	0.028	0.032	-10000	0	-0.52	1	1
RAPGEF1	0.01	0.024	-10000	0	-0.58	1	1
BDNF	-0.021	0.13	-10000	0	-0.52	36	36
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
DYNLT1	0.011	0	-10000	0	-10000	0	0
NTRK1	-0.038	0.16	-10000	0	-0.53	53	53
NTRK2	-0.18	0.25	-10000	0	-0.5	220	220
NTRK3	-0.043	0.16	-10000	0	-0.51	60	60
NT-4/5 (dimer)/TRKB	-0.16	0.2	-10000	0	-0.34	297	297
neuron apoptosis	0.14	0.19	0.45	118	-10000	0	118
SHC 2-3/Grb2	-0.15	0.21	-10000	0	-0.5	118	118
SHC1	0.011	0	-10000	0	-10000	0	0
SHC2	-0.13	0.2	-10000	0	-0.55	83	83
SHC3	-0.14	0.21	-10000	0	-0.57	88	88
STAT3 (dimer)	0.018	0.015	-10000	0	-0.35	1	1
NT3 (dimer)/TRKA	-0.081	0.18	-10000	0	-0.36	160	160
RIN/GDP	-0.004	0.07	-10000	0	-0.27	10	10
GIPC1	0.007	0.048	-10000	0	-0.58	4	4
KRAS	0.006	0.057	-10000	0	-0.56	6	6
DNAJA3	-0.058	0.14	-10000	0	-0.36	68	68
RIN/GTP	-0.001	0.019	-10000	0	-0.32	2	2
CCND1	0.024	0.034	-10000	0	-0.81	1	1
MAGED1	0.011	0	-10000	0	-10000	0	0
PTPN11	0.006	0.054	-10000	0	-0.58	5	5
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.014	0.09	-10000	0	-0.46	23	23
SHC/GRB2/SOS1	0.023	0.015	-10000	0	-0.35	1	1
GRB2	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.079	0.19	-10000	0	-0.38	150	150
TRKA/NEDD4-2	-0.02	0.11	-10000	0	-0.38	54	54
ELMO1	0.004	0.063	-10000	0	-0.5	9	9
RhoG/GTP/ELMO1/DOCK1	0.01	0.041	-10000	0	-0.3	10	10
NGF	-0.032	0.14	-10000	0	-0.52	47	47
HRAS	0.008	0.041	-10000	0	-0.49	4	4
DOCK1	0.01	0.024	-10000	0	-0.58	1	1
GAB2	0.009	0.034	-10000	0	-0.58	2	2
RIT2	-0.001	0.027	-10000	0	-0.46	2	2
RIT1	0.011	0	-10000	0	-10000	0	0
FRS2	0.009	0.034	-10000	0	-0.58	2	2
DNM1	-0.006	0.093	-10000	0	-0.5	20	20
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.011	0.019	-10000	0	-0.46	1	1
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.07	0.14	-10000	0	-0.36	73	73
mol:GDP	-0.007	0.099	-10000	0	-0.39	12	12
NGF (dimer)	-0.032	0.14	-10000	0	-0.52	47	47
RhoG/GDP	0.003	0.045	-10000	0	-0.36	9	9
RIT1/GDP	0.002	0.07	-10000	0	-0.27	8	8
TIAM1	-0.044	0.16	-10000	0	-0.52	62	62
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
BDNF (dimer)/TRKB	-0.11	0.18	-10000	0	-0.32	239	239
KIDINS220/CRKL/C3G	0.016	0.018	-10000	0	-0.42	1	1
SHC/RasGAP	0.015	0.025	-10000	0	-0.42	2	2
FRS2 family/SHP2	0.018	0.052	-10000	0	-0.44	7	7
SHC/GRB2/SOS1/GAB1	0.029	0.014	-10000	0	-0.32	1	1
RIT1/GTP	0.008	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.02	0.13	-10000	0	-0.53	34	34
RAP1/GDP	-0.021	0.046	-10000	0	-0.27	5	5
KIDINS220/CRKL	0.011	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.021	0.13	-10000	0	-0.52	36	36
ubiquitin-dependent protein catabolic process	-0.035	0.14	-10000	0	-0.34	91	91
Schwann cell development	-0.032	0.032	-10000	0	-10000	0	0
EHD4	0.011	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.027	0.03	-10000	0	-0.32	4	4
FRS2 family/SHP2/CRK family/C3G/GAB2	0.028	0.049	-10000	0	-0.42	6	6
RAP1B	0.011	0	-10000	0	-10000	0	0
RAP1A	0.01	0.024	-10000	0	-0.58	1	1
CDC42/GTP	-0.13	0.16	-10000	0	-0.47	66	66
ABL1	0.01	0.024	-10000	0	-0.58	1	1
SH2B family/GRB2/SOS1	0.016	0.018	-10000	0	-0.42	1	1
Rap1/GTP	-0.018	0.081	-10000	0	-0.39	3	3
STAT3	0.018	0.015	-10000	0	-0.35	1	1
axon guidance	-0.13	0.15	-10000	0	-0.45	66	66
MAPK3	-0.067	0.17	-10000	0	-0.39	106	106
MAPK1	-0.067	0.17	-10000	0	-0.38	107	107
CDC42/GDP	0	0.074	-10000	0	-0.35	6	6
NTF3	-0.02	0.13	-10000	0	-0.53	34	34
NTF4	-0.014	0.09	-10000	0	-0.46	23	23
NGF (dimer)/TRKA/FAIM	-0.037	0.14	-10000	0	-0.35	95	95
PI3K	0.013	0.04	-10000	0	-0.42	5	5
FRS3	0.01	0.031	-10000	0	-0.52	2	2
FAIM	0.006	0.057	-10000	0	-0.56	6	6
GAB1	0.011	0	-10000	0	-10000	0	0
RASGRF1	-0.092	0.17	-10000	0	-0.34	144	144
SOS1	0.01	0.024	-10000	0	-0.58	1	1
MCF2L	-0.033	0.13	-10000	0	-0.32	94	94
RGS19	-0.002	0.085	-10000	0	-0.55	14	14
CDC42	0.006	0.054	-10000	0	-0.58	5	5
RAS family/GTP	-0.003	0.095	-10000	0	-0.56	8	8
Rac1/GDP	0.002	0.07	-10000	0	-0.28	7	7
NGF (dimer)/TRKA/GRIT	-0.041	0.14	-10000	0	-0.35	90	90
neuron projection morphogenesis	-0.041	0.13	-10000	0	-0.61	9	9
NGF (dimer)/TRKA/NEDD4-2	-0.034	0.14	-10000	0	-0.35	91	91
MAP2K1	0.03	0.023	-10000	0	-0.29	3	3
NGFR	-0.079	0.2	-10000	0	-0.51	104	104
NGF (dimer)/TRKA/GIPC/GAIP	-0.022	0.12	-10000	0	-0.28	81	81
RAS family/GTP/PI3K	0.014	0.08	-10000	0	-0.42	15	15
FRS2 family/SHP2/GRB2/SOS1	0.029	0.047	-10000	0	-0.36	8	8
NRAS	0.001	0.076	-10000	0	-0.58	10	10
GRB2/SOS1	0.016	0.018	-10000	0	-0.42	1	1
PRKCI	0.008	0.042	-10000	0	-0.58	3	3
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.031	-10000	0	-0.52	2	2
MAPKKK cascade	-0.09	0.19	-10000	0	-0.63	59	59
RASA1	0.009	0.034	-10000	0	-0.58	2	2
TRKA/c-Abl	-0.02	0.12	-10000	0	-0.38	54	54
SQSTM1	0.011	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.098	0.16	-10000	0	-0.36	105	105
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.018	0.12	-10000	0	-0.33	64	64
MATK	-0.064	0.19	-10000	0	-0.52	84	84
NEDD4L	0.01	0.024	-10000	0	-0.58	1	1
RAS family/GDP	-0.021	0.049	-10000	0	-0.27	8	8
NGF (dimer)/TRKA	-0.076	0.14	-10000	0	-0.33	112	112
Rac1/GTP	-0.079	0.11	-10000	0	-0.33	65	65
FRS2 family/SHP2/CRK family	0.029	0.049	-10000	0	-0.4	7	7

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.016	0.1	-9999	-0.28	71	71
RGS9BP	-0.009	0.1	-9999	-0.54	21	21
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.003	0.046	-9999	-0.46	6	6
mol:Na +	-0.047	0.12	-9999	-0.3	107	107
mol:ADP	-0.002	0.057	-9999	-0.34	16	16
GNAT2	-0.007	0.095	-9999	-0.53	19	19
RGS9-1/Gbeta5/R9AP	-0.022	0.12	-9999	-0.32	75	75
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.004	0.06	-9999	-0.32	20	20
GRK7	-0.001	0.063	-9999	-0.46	11	11
CNGB3	-0.029	0.12	-9999	-0.46	42	42
Cone Metarhodopsin II/X-Arrestin	-0.001	0.03	-9999	-0.32	5	5
mol:Ca2+	-0.049	0.12	-9999	-0.28	123	123
Cone PDE6	-0.018	0.1	-9999	-0.32	43	43
Cone Metarhodopsin II	-0.001	0.044	-9999	-0.26	16	16
Na + (4 Units)	-0.048	0.12	-9999	-0.28	123	123
GNAT2/GDP	-0.021	0.11	-9999	-0.31	55	55
GNB5	0.007	0.048	-9999	-0.58	4	4
mol:GMP (4 units)	-0.004	0.058	-9999	-0.28	24	24
Cone Transducin	-0.017	0.11	-9999	-0.3	71	71
SLC24A2	-0.011	0.092	-9999	-0.48	22	22
GNB3/GNGT2	-0.02	0.12	-9999	-0.39	53	53
GNB3	-0.019	0.12	-9999	-0.53	33	33
GNAT2/GTP	-0.005	0.07	-9999	-0.38	19	19
CNGA3	-0.05	0.17	-9999	-0.52	66	66
ARR3	-0.001	0.042	-9999	-0.46	5	5
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.047	0.12	-9999	-0.3	107	107
mol:Pi	-0.022	0.12	-9999	-0.32	75	75
Cone CNG Channel	-0.053	0.11	-9999	-0.32	42	42
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.011	0.092	-9999	-0.48	22	22
RGS9	-0.036	0.15	-9999	-0.52	52	52
PDE6C	0	0.038	-9999	-0.46	4	4
GNGT2	-0.009	0.1	-9999	-0.56	21	21
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0	0.019	-9999	-0.46	1	1

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.047	0.19	-9999	-0.49	74	74
MAP4K1	-0.044	0.17	-9999	-0.55	59	59
MAP3K8	0.01	0.031	-9999	-0.52	2	2
PRKCB	-0.041	0.16	-9999	-0.54	56	56
DBNL	0.01	0.024	-9999	-0.58	1	1
CRKL	0.011	0	-9999	-10000	0	0
MAP3K1	-0.021	0.15	-9999	-0.53	38	38
JUN	-0.031	0.2	-9999	-0.71	41	41
MAP3K7	-0.018	0.15	-9999	-0.55	33	33
GRAP2	-0.024	0.14	-9999	-0.55	37	37
CRK	0.011	0.019	-9999	-0.46	1	1
MAP2K4	-0.014	0.15	-9999	-0.53	35	35
LAT	-0.01	0.1	-9999	-0.51	24	24
LCP2	-0.014	0.12	-9999	-0.54	27	27
MAPK8	-0.037	0.2	-9999	-0.76	39	39
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.025	0.16	-9999	-0.48	48	48
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.039	0.18	-9999	-0.46	74	74

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.015	0.025	-10000	0	-10000	0	0
AES	0.013	0.032	-10000	0	-0.58	1	1
FBXW11	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.014	0.039	-10000	0	-0.4	5	5
SMAD4	0.004	0.064	-10000	0	-0.58	7	7
DKK2	-0.087	0.21	-10000	0	-0.54	106	106
TLE1	0.01	0.053	-10000	0	-0.58	4	4
MACF1	0.012	0	-10000	0	-10000	0	0
CTNNB1	0.05	0.099	0.25	13	-0.95	2	15
WIF1	-0.18	0.25	-10000	0	-0.5	222	222
beta catenin/RanBP3	0.025	0.13	0.39	58	-0.7	2	60
KREMEN2	-0.038	0.15	-10000	0	-0.48	60	60
DKK1	-0.15	0.24	-10000	0	-0.51	185	185
beta catenin/beta TrCP1	0.054	0.091	0.25	11	-0.8	2	13
FZD1	0.009	0.039	-10000	0	-0.54	3	3
AXIN2	-0.11	0.42	-10000	0	-1.4	54	54
AXIN1	0.011	0.024	-10000	0	-0.58	1	1
RAN	0.012	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.014	0.082	-10000	0	-0.95	3	3
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.049	0.1	-10000	0	-0.62	7	7
Axin1/APC/GSK3	0.046	0.079	0.22	17	-0.78	2	19
Axin1/APC/GSK3/beta catenin/Macf1	0.036	0.094	-10000	0	-0.71	4	4
HNF1A	0.008	0.058	-10000	0	-0.53	6	6
CTBP1	0.013	0.033	-10000	0	-0.58	1	1
MYC	-0.013	0.15	-10000	0	-1.5	5	5
RANBP3	0.011	0.024	-10000	0	-0.58	1	1
DKK2/LRP6/Kremen 2	-0.069	0.16	-10000	0	-0.32	159	159
NKD1	-0.13	0.24	-10000	0	-0.52	158	158
TCF4	0.001	0.085	-10000	0	-0.52	14	14
TCF3	0.013	0.033	-10000	0	-0.58	1	1
WNT1/LRP6/FZD1/Axin1	0.016	0.061	-10000	0	-0.36	6	6
Ran/GTP	0.009	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.028	0.16	0.46	51	-0.62	6	57
LEF1	-0.009	0.11	-10000	0	-0.52	26	26
DVL1	0.045	0.061	0.21	1	-0.5	4	5
CSNK2A1	0.012	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.042	0.11	-10000	0	-0.52	11	11
DKK1/LRP6/Kremen 2	-0.11	0.18	-10000	0	-0.32	225	225
LRP6	0.01	0.035	-10000	0	-0.58	2	2
CSNK1A1	0.013	0.043	-10000	0	-0.59	2	2
NLK	0.011	0.004	-10000	0	-10000	0	0
CCND1	-0.005	0.093	-10000	0	-0.73	4	4
WNT1	-0.009	0.087	-10000	0	-0.46	21	21
GSK3A	0.012	0.001	-10000	0	-10000	0	0
GSK3B	0.009	0.034	-10000	0	-0.58	2	2
FRAT1	0.01	0.024	-10000	0	-0.58	1	1
PPP2R5D	0.088	0.11	0.27	154	-10000	0	154
APC	0.01	0.083	-10000	0	-0.33	24	24
WNT1/LRP6/FZD1	0.071	0.1	0.23	78	-0.69	3	81
CREBBP	0.014	0.022	-10000	0	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.015	0.12	-9999	-0.38	40	40
NF kappa B1 p50/RelA/I kappa B alpha	-0.014	0.11	-9999	-0.38	16	16
AP1	-0.085	0.14	-9999	-0.44	48	48
mol:PIP3	-0.065	0.12	-9999	-0.49	24	24
AKT1	0.01	0.091	-9999	-0.42	12	12
PTK2B	-0.014	0.094	-9999	-0.31	27	27
RHOA	0.01	0.051	-9999	-0.35	3	3
PIK3CB	0.008	0.046	-9999	-0.55	4	4
mol:Ca2+	-0.018	0.11	-9999	-0.39	18	18
MAGI3	0.008	0.042	-9999	-0.58	3	3
RELA	0.011	0	-9999	-10000	0	0
apoptosis	-0.052	0.14	-9999	-0.35	79	79
HRAS/GDP	0.006	0.03	-9999	-0.35	4	4
positive regulation of microtubule depolymerization	-0.044	0.13	-9999	-0.33	55	55
NF kappa B1 p50/RelA	-0.064	0.12	-9999	-0.48	28	28
endothelial cell migration	-0.046	0.19	-9999	-0.51	77	77
ADCY4	-0.039	0.16	-9999	-0.5	46	46
ADCY5	-0.072	0.19	-9999	-0.56	60	60
ADCY6	-0.037	0.16	-9999	-0.51	43	43
ADCY7	-0.038	0.16	-9999	-0.52	43	43
ADCY1	-0.049	0.16	-9999	-0.51	49	49
ADCY2	-0.054	0.18	-9999	-0.52	63	63
ADCY3	-0.037	0.16	-9999	-0.51	44	44
ADCY8	-0.042	0.16	-9999	-0.52	43	43
ADCY9	-0.038	0.16	-9999	-0.51	44	44
GSK3B	-0.009	0.092	-9999	-0.33	22	22
arachidonic acid secretion	-0.033	0.15	-9999	-0.48	44	44
GNG2	0.004	0.063	-9999	-0.53	8	8
TRIP6	-0.014	0.12	-9999	-0.42	40	40
GNAO1	-0.054	0.16	-9999	-0.34	117	117
HRAS	0.008	0.041	-9999	-0.49	4	4
NFKBIA	-0.02	0.12	-9999	-0.4	24	24
GAB1	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.032	0.2	-9999	-0.91	30	30
JUN	0.006	0.052	-9999	-0.56	5	5
LPA/LPA2/NHERF2	0.007	0.046	-9999	-0.32	7	7
TIAM1	-0.059	0.24	-9999	-1.1	30	30
PIK3R1	0.008	0.042	-9999	-0.58	3	3
mol:IP3	-0.019	0.11	-9999	-0.4	18	18
PLCB3	0.012	0.055	-9999	-0.36	8	8
FOS	-0.026	0.14	-9999	-0.53	41	41
positive regulation of mitosis	-0.033	0.15	-9999	-0.48	44	44
LPA/LPA1-2-3	-0.063	0.15	-9999	-0.38	75	75
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0.001	-9999	-10000	0	0
BCAR1	0.008	0.044	-9999	-0.52	4	4
stress fiber formation	-0.023	0.11	-9999	-0.35	28	28
GNAZ	-0.034	0.14	-9999	-0.36	78	78
EGFR/PI3K-beta/Gab1	-0.067	0.13	-9999	-0.52	24	24
positive regulation of dendritic cell cytokine production	-0.063	0.15	-9999	-0.38	75	75
LPA/LPA2/MAGI-3	0.006	0.05	-9999	-0.33	9	9
ARHGEF1	-0.007	0.11	-9999	-0.34	38	38
GNAI2	-0.02	0.12	-9999	-0.35	57	57
GNAI3	-0.02	0.12	-9999	-0.35	57	57
GNAI1	-0.028	0.14	-9999	-0.38	65	65
LPA/LPA3	-0.056	0.14	-9999	-0.37	91	91
LPA/LPA2	-0.002	0.047	-9999	-0.34	7	7
LPA/LPA1	-0.034	0.14	-9999	-0.37	77	77
HB-EGF/EGFR	-0.035	0.12	-9999	-0.37	48	48
HBEGF	-0.041	0.14	-9999	-0.37	90	90
mol:DAG	-0.019	0.11	-9999	-0.4	18	18
cAMP biosynthetic process	-0.051	0.17	-9999	-0.49	58	58
NFKB1	0.01	0.024	-9999	-0.58	1	1
SRC	0.01	0.024	-9999	-0.58	1	1
GNB1	0.011	0.001	-9999	-10000	0	0
LYN	-0.02	0.12	-9999	-0.4	24	24
GNAQ	-0.031	0.1	-9999	-0.32	47	47
LPAR2	0.006	0.053	-9999	-0.47	7	7
LPAR3	-0.07	0.19	-9999	-0.51	91	91
LPAR1	-0.033	0.15	-9999	-0.61	35	35
IL8	-0.11	0.21	-9999	-0.46	115	115
PTK2	-0.051	0.15	-9999	-0.36	73	73
Rac1/GDP	0.008	0	-9999	-10000	0	0
CASP3	-0.053	0.14	-9999	-0.35	79	79
EGFR	0.004	0.063	-9999	-0.53	8	8
PLCG1	-0.032	0.12	-9999	-0.34	52	52
PLD2	-0.05	0.14	-9999	-0.36	72	72
G12/G13	-0.011	0.11	-9999	-0.37	36	36
PI3K-beta	-0.03	0.087	-9999	-0.43	16	16
cell migration	-0.018	0.088	-9999	-0.26	40	40
SLC9A3R2	0.01	0.024	-9999	-0.58	1	1
PXN	-0.023	0.11	-9999	-0.36	28	28
HRAS/GTP	-0.034	0.16	-9999	-0.5	44	44
RAC1	0.011	0	-9999	-10000	0	0
MMP9	-0.059	0.18	-9999	-0.52	79	79
PRKCE	0.011	0	-9999	-10000	0	0
PRKCD	-0.012	0.11	-9999	-0.42	13	13
Gi(beta/gamma)	-0.033	0.15	-9999	-0.49	44	44
mol:LPA	-0.01	0.045	-9999	-0.19	22	22
TRIP6/p130 Cas/FAK1/Paxillin	-0.074	0.14	-9999	-0.48	32	32
MAPKKK cascade	-0.033	0.15	-9999	-0.48	44	44
contractile ring contraction involved in cytokinesis	0.01	0.051	-9999	-0.34	3	3
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.038	0.12	-9999	-0.33	59	59
GNA15	-0.038	0.11	-9999	-0.32	61	61
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.009	0.034	-9999	-0.58	2	2
MAPT	-0.045	0.13	-9999	-0.34	55	55
GNA11	-0.03	0.1	-9999	-0.32	45	45
Rac1/GTP	-0.034	0.22	-9999	-0.96	30	30
MMP2	-0.046	0.19	-9999	-0.52	77	77

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.002	0.051	-9999	-0.34	13	13
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.03	0.12	-9999	-0.36	69	69
STXBP1	-0.007	0.1	-9999	-0.56	19	19
ACh/CHRNA1	-0.025	0.1	-9999	-0.35	47	47
RAB3GAP2/RIMS1/UNC13B	-0.019	0.11	-9999	-0.3	72	72
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	-0.052	0.16	-9999	-0.51	68	68
mol:ACh	-0.007	0.035	-9999	-0.12	29	29
RAB3GAP2	0.008	0.042	-9999	-0.58	3	3
STX1A/SNAP25/VAMP2	-0.049	0.1	-9999	-0.33	35	35
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.025	0.1	-9999	-0.35	47	47
UNC13B	0.01	0.031	-9999	-0.52	2	2
CHRNA1	-0.031	0.15	-9999	-0.53	47	47
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.086	0.16	-9999	-0.38	137	137
SNAP25	-0.022	0.074	-9999	-0.2	82	82
VAMP2	0.005	0	-9999	-10000	0	0
SYT1	-0.12	0.24	-9999	-0.57	137	137
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.002	0.076	-9999	-0.32	32	32
STX1A/SNAP25 fragment 1/VAMP2	-0.049	0.1	-9999	-0.33	35	35

×

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

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
MAP4K1	-0.032	0.14	-10000	0	-0.41	46	46
CRKL	-0.012	0.12	-10000	0	-0.42	38	38
HRAS	-0.025	0.15	-10000	0	-0.47	37	37
mol:PIP3	-0.021	0.12	-10000	0	-0.4	39	39
SPRED1	0.005	0.059	-10000	0	-0.58	6	6
SPRED2	0.008	0.042	-10000	0	-0.58	3	3
GAB1	-0.019	0.13	-10000	0	-0.44	39	39
FOXO3	-0.007	0.12	-10000	0	-0.38	40	40
AKT1	-0.014	0.13	-10000	0	-0.41	41	41
BAD	-0.008	0.12	-10000	0	-0.39	40	40
megakaryocyte differentiation	-0.082	0.18	-10000	0	-0.36	133	133
GSK3B	-0.008	0.12	-10000	0	-0.39	41	41
RAF1	-0.013	0.13	-10000	0	-0.39	31	31
SHC1	0.011	0	-10000	0	-10000	0	0
STAT3	-0.019	0.13	-10000	0	-0.44	39	39
STAT1	-0.064	0.32	-10000	0	-1	50	50
HRAS/SPRED1	-0.016	0.13	-10000	0	-0.4	37	37
cell proliferation	-0.018	0.13	-10000	0	-0.43	39	39
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
TEC	0.011	0.019	-10000	0	-0.46	1	1
RPS6KB1	-0.02	0.14	-10000	0	-0.44	46	46
HRAS/SPRED2	-0.015	0.13	-10000	0	-0.39	34	34
LYN/TEC/p62DOK	-0.007	0.12	-10000	0	-0.41	38	38
MAPK3	0.001	0.096	-10000	0	-0.28	29	29
STAP1	-0.051	0.17	-10000	0	-0.5	53	53
GRAP2	-0.024	0.14	-10000	0	-0.55	37	37
JAK2	-0.056	0.29	-10000	0	-0.97	42	42
STAT1 (dimer)	-0.061	0.31	-10000	0	-0.98	50	50
mol:Gleevec	0	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.043	0.16	-10000	0	-0.47	53	53
actin filament polymerization	-0.03	0.14	-10000	0	-0.41	55	55
LYN	0.011	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.058	0.22	-10000	0	-0.64	56	56
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
CBL/CRKL/GRB2	0.001	0.12	-10000	0	-0.38	34	34
PI3K	-0.011	0.14	-10000	0	-0.45	40	40
PTEN	0.005	0.059	-10000	0	-0.58	6	6
SCF/KIT/EPO/EPOR	-0.066	0.35	-10000	0	-1.3	37	37
MAPK8	-0.019	0.13	-10000	0	-0.44	39	39
STAT3 (dimer)	-0.018	0.13	-10000	0	-0.43	39	39
positive regulation of transcription	0.005	0.081	-10000	0	-0.24	19	19
mol:GDP	-0.035	0.16	-10000	0	-0.45	58	58
PIK3C2B	-0.018	0.13	-10000	0	-0.44	39	39
CBL/CRKL	-0.004	0.12	-10000	0	-0.39	38	38
FER	-0.023	0.14	-10000	0	-0.46	42	42
SH2B3	-0.019	0.13	-10000	0	-0.43	41	41
PDPK1	-0.014	0.11	-10000	0	-0.38	38	38
SNAI2	-0.027	0.14	-10000	0	-0.43	49	49
positive regulation of cell proliferation	-0.04	0.23	-10000	0	-0.7	52	52
KITLG	-0.005	0.1	-10000	0	-0.6	17	17
cell motility	-0.04	0.23	-10000	0	-0.7	52	52
PTPN6	0.011	0.007	-10000	0	-10000	0	0
EPOR	-0.001	0.14	-10000	0	-1.2	4	4
STAT5A (dimer)	-0.031	0.19	-10000	0	-0.62	46	46
SOCS1	-0.028	0.14	-10000	0	-0.49	47	47
cell migration	0.055	0.16	0.47	50	-10000	0	50
SOS1	0.01	0.024	-10000	0	-0.58	1	1
EPO	0	0.054	-10000	0	-0.46	8	8
VAV1	-0.026	0.14	-10000	0	-0.57	38	38
GRB10	-0.021	0.14	-10000	0	-0.44	42	42
PTPN11	0.006	0.054	-10000	0	-0.57	5	5
SCF/KIT	-0.026	0.14	0.22	1	-0.44	47	48
GO:0007205	0	0.007	-10000	0	-10000	0	0
MAP2K1	-0.003	0.1	-10000	0	-0.31	31	31
CBL	0.011	0	-10000	0	-10000	0	0
KIT	-0.067	0.33	-10000	0	-1.4	33	33
MAP2K2	-0.002	0.1	-10000	0	-0.31	28	28
SHC/Grb2/SOS1	-0.007	0.13	-10000	0	-0.42	38	38
STAT5A	-0.033	0.2	-10000	0	-0.64	46	46
GRB2	0.011	0	-10000	0	-10000	0	0
response to radiation	-0.026	0.14	-10000	0	-0.42	49	49
SHC/GRAP2	-0.009	0.1	-10000	0	-0.4	37	37
PTPRO	-0.084	0.18	-10000	0	-0.36	133	133
SH2B2	-0.031	0.15	-10000	0	-0.42	55	55
DOK1	0.011	0	-10000	0	-10000	0	0
MATK	-0.056	0.16	-10000	0	-0.48	50	50
CREBBP	0.022	0.031	-10000	0	-10000	0	0
BCL2	-0.021	0.24	-10000	0	-1.3	16	16

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.028	0.12	0.19	2	-0.34	59	61
ACTA1	-0.049	0.16	0.22	3	-0.42	66	69
NUMA1	-0.027	0.12	0.19	2	-0.33	61	63
SPTAN1	-0.041	0.15	0.23	2	-0.41	62	64
LIMK1	-0.041	0.15	0.23	2	-0.41	61	63
BIRC3	-0.016	0.12	-10000	0	-0.52	30	30
BIRC2	-0.002	0.087	-10000	0	-0.58	13	13
BAX	0.01	0.024	-10000	0	-0.58	1	1
CASP10	-0.055	0.16	-10000	0	-0.34	129	129
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.01	0.024	-10000	0	-0.58	1	1
PTK2	-0.027	0.12	0.19	2	-0.34	60	62
DIABLO	0.011	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.04	0.15	0.23	2	-0.4	62	64
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.01	0.024	-10000	0	-0.58	1	1
GSN	-0.046	0.16	0.23	2	-0.42	64	66
MADD	0.011	0	-10000	0	-10000	0	0
TFAP2A	-0.085	0.2	-10000	0	-0.56	84	84
BID	-0.022	0.086	-10000	0	-0.23	64	64
MAP3K1	-0.014	0.07	-10000	0	-0.31	14	14
TRADD	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.014	0.036	-10000	0	-0.42	4	4
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.042	0.16	0.23	2	-0.42	61	63
CASP9	0.011	0.024	-10000	0	-0.58	1	1
DNA repair	0.004	0.049	0.15	8	-0.18	11	19
neuron apoptosis	0.012	0.036	-10000	0	-0.49	2	2
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.033	0.15	0.22	2	-0.4	59	61
APAF1	0.008	0.042	-10000	0	-0.58	3	3
CASP6	-0.005	0.085	-10000	0	-0.52	5	5
TRAF2	0.01	0.024	-10000	0	-0.58	1	1
ICAD/CAD	-0.034	0.15	0.22	2	-0.4	58	60
CASP7	0.009	0.058	0.27	20	-10000	0	20
KRT18	0.006	0.033	-10000	0	-0.55	1	1
apoptosis	-0.038	0.14	0.25	2	-0.37	67	69
DFFA	-0.04	0.15	0.23	2	-0.42	59	61
DFFB	-0.04	0.15	0.23	2	-0.42	60	62
PARP1	-0.004	0.049	0.18	11	-0.15	8	19
actin filament polymerization	0.042	0.15	0.38	68	-0.22	2	70
TNF	-0.017	0.12	-10000	0	-0.54	30	30
CYCS	-0.022	0.086	-10000	0	-0.28	36	36
SATB1	-0.019	0.11	-10000	0	-0.41	20	20
SLK	-0.052	0.16	0.23	2	-0.41	76	78
p15 BID/BAX	-0.014	0.078	-10000	0	-0.3	13	13
CASP2	0.022	0.06	-10000	0	-0.4	2	2
JNK cascade	0.014	0.07	0.31	14	-10000	0	14
CASP3	-0.049	0.16	0.23	3	-0.44	63	66
LMNB2	0.016	0.061	-10000	0	-0.36	6	6
RIPK1	0.011	0	-10000	0	-10000	0	0
CASP4	0.009	0.039	-10000	0	-0.54	3	3
Mammalian IAPs/DIABLO	0.006	0.1	-10000	0	-0.45	21	21
negative regulation of DNA binding	-0.084	0.2	-10000	0	-0.55	84	84
stress fiber formation	-0.051	0.16	0.23	2	-0.41	76	78
GZMB	-0.073	0.18	-10000	0	-0.4	128	128
CASP1	-0.006	0.079	-10000	0	-0.3	38	38
LMNB1	0.017	0.054	-10000	0	-0.27	5	5
APP	0.012	0.037	-10000	0	-0.5	2	2
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.008	0.018	-10000	0	-0.43	1	1
VIM	-0.031	0.13	0.23	5	-0.35	61	66
LMNA	0.017	0.059	-10000	0	-0.35	5	5
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.017	0.064	-10000	0	-0.43	2	2
LRDD	0.008	0.042	-10000	0	-0.58	3	3
SREBF1	-0.042	0.15	0.23	2	-0.41	63	65
APAF-1/Caspase 9	-0.003	0.065	0.4	7	-0.75	1	8
nuclear fragmentation during apoptosis	-0.026	0.12	0.19	2	-0.33	61	63
CFL2	-0.044	0.15	0.22	2	-0.39	68	70
GAS2	-0.071	0.17	0.23	1	-0.41	94	95
positive regulation of apoptosis	0.02	0.059	-10000	0	-0.32	6	6
PRF1	-0.039	0.15	-10000	0	-0.5	58	58

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.009	0.034	-9999	-0.58	2	2
GNAT1/GTP	0.001	0.019	-9999	-0.32	2	2
Metarhodopsin II/Arrestin	0	0.023	-9999	-0.27	4	4
PDE6G/GNAT1/GTP	-0.015	0.088	-9999	-0.33	42	42
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.001	0.027	-9999	-0.46	2	2
GRK1	-0.003	0.046	-9999	-0.46	6	6
CNG Channel	-0.12	0.18	-9999	-0.42	99	99
mol:Na +	-0.067	0.13	-9999	-0.5	24	24
mol:ADP	-0.003	0.046	-9999	-0.46	6	6
RGS9-1/Gbeta5/R9AP	-0.022	0.12	-9999	-0.32	75	75
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.069	0.14	-9999	-0.51	24	24
CNGB1	-0.005	0.068	-9999	-0.46	13	13
RDH5	0	0.079	-9999	-0.52	13	13
SAG	0.002	0.019	-9999	-0.46	1	1
mol:Ca2+	-0.044	0.14	-9999	-0.48	24	24
Na + (4 Units)	-0.064	0.12	-9999	-0.46	24	24
RGS9	-0.036	0.15	-9999	-0.52	52	52
GNB1/GNGT1	-0.023	0.12	-9999	-0.37	58	58
GNAT1/GDP	-0.018	0.1	-9999	-0.32	45	45
GUCY2D	-0.015	0.1	-9999	-0.46	29	29
GNGT1	-0.043	0.16	-9999	-0.52	58	58
GUCY2F	0	0.019	-9999	-0.46	1	1
GNB5	0.007	0.048	-9999	-0.58	4	4
mol:GMP (4 units)	-0.083	0.17	-9999	-0.36	123	123
mol:11-cis-retinal	0	0.079	-9999	-0.52	13	13
mol:cGMP	-0.025	0.11	-9999	-0.34	36	36
GNB1	0.011	0	-9999	-10000	0	0
Rhodopsin	-0.001	0.062	-9999	-0.37	16	16
SLC24A1	0.009	0.034	-9999	-0.58	2	2
CNGA1	-0.052	0.17	-9999	-0.52	70	70
Metarhodopsin II	-0.002	0.033	-9999	-0.28	8	8
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.027	0.11	-9999	-0.35	36	36
RGS9BP	-0.009	0.1	-9999	-0.54	21	21
Metarhodopsin II/Transducin	-0.012	0.071	-9999	-0.28	33	33
GCAP Family/Ca ++	-0.02	0.094	-9999	-0.28	65	65
PDE6A/B	-0.096	0.2	-9999	-0.41	157	157
mol:Pi	-0.022	0.12	-9999	-0.32	75	75
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.016	0.092	-9999	-0.29	59	59
PDE6B	-0.03	0.14	-9999	-0.52	46	46
PDE6A	-0.1	0.22	-9999	-0.54	125	125
PDE6G	-0.026	0.14	-9999	-0.54	40	40
RHO	-0.001	0.032	-9999	-0.46	3	3
PDE6	-0.12	0.18	-9999	-0.55	50	50
GUCA1A	-0.022	0.12	-9999	-0.49	36	36
GC2/GCAP Family	-0.02	0.096	-9999	-0.34	32	32
GUCA1C	-0.001	0.026	-9999	-0.46	2	2
GUCA1B	-0.015	0.12	-9999	-0.54	28	28

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.009	0.1	-9999	-0.5	23	23
GPC2	-0.008	0.1	-9999	-0.55	20	20
GPC2/Midkine	-0.011	0.1	-9999	-0.38	42	42
neuron projection morphogenesis	-0.011	0.1	-9999	-0.38	42	42

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.045	0.17	-10000	0	-0.53	62	62
ANTXR2	0.005	0.058	-10000	0	-0.53	7	7
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.008	0.022	-10000	0	-0.068	68	68
monocyte activation	-0.025	0.13	-10000	0	-0.49	38	38
MAP2K2	-0.004	0.032	-10000	0	-0.76	1	1
MAP2K1	-0.008	0.027	-10000	0	-0.35	2	2
MAP2K7	-0.007	0.022	-10000	0	-0.31	1	1
MAP2K6	-0.012	0.045	-10000	0	-0.32	10	10
CYAA	-0.021	0.094	-10000	0	-0.28	68	68
MAP2K4	-0.008	0.029	-10000	0	-0.31	3	3
IL1B	-0.04	0.11	-10000	0	-0.28	86	86
Channel	-0.021	0.1	-10000	0	-0.3	68	68
NLRP1	-0.02	0.065	-10000	0	-0.28	31	31
CALM1	0.011	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.009	0.025	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.008	0.022	0.068	68	-10000	0	68
MAPK3	-0.007	0.022	-10000	0	-0.31	1	1
MAPK1	-0.007	0.024	-10000	0	-0.38	1	1
PGR	-0.041	0.099	-10000	0	-0.29	77	77
PA/Cellular Receptors	-0.024	0.11	-10000	0	-0.33	68	68
apoptosis	-0.008	0.022	-10000	0	-0.068	68	68
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.019	0.093	-10000	0	-0.27	68	68
macrophage activation	0.007	0.028	-10000	0	-0.33	2	2
TNF	-0.017	0.12	-10000	0	-0.54	30	30
VCAM1	-0.025	0.14	-10000	0	-0.49	38	38
platelet activation	-0.009	0.025	-10000	0	-10000	0	0
MAPKKK cascade	-0.002	0.027	0.14	4	-10000	0	4
IL18	-0.008	0.055	-10000	0	-0.25	19	19
negative regulation of macrophage activation	-0.008	0.022	-10000	0	-0.068	68	68
LEF	-0.008	0.022	-10000	0	-0.069	68	68
CASP1	-0.017	0.041	-10000	0	-0.16	32	32
mol:cAMP	-0.009	0.025	-10000	0	-10000	0	0
necrosis	-0.008	0.022	-10000	0	-0.068	68	68
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.019	0.095	-10000	0	-0.28	68	68
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt 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
Delta 1/NOTCH/NOTCH(cleaved)	-0.018	0.091	-10000	0	-0.63	10	10
HDAC1	0.008	0.004	-10000	0	-10000	0	0
AES	0.01	0.024	-10000	0	-0.58	1	1
FBXW11	0.011	0	-10000	0	-10000	0	0
DTX1	-0.01	0.11	-10000	0	-0.54	23	23
LRP6/FZD1	0.014	0.038	-10000	0	-0.4	5	5
TLE1	0.007	0.048	-10000	0	-0.58	4	4
AP1	-0.061	0.13	-10000	0	-0.3	112	112
NCSTN	0.011	0	-10000	0	-10000	0	0
ADAM10	0.006	0.054	-10000	0	-0.58	5	5
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.036	0.067	-10000	0	-1.3	1	1
NICD/RBPSUH	0.016	0.085	-10000	0	-0.65	9	9
WIF1	-0.18	0.25	-10000	0	-0.5	222	222
NOTCH1	-0.012	0.078	-10000	0	-0.63	9	9
PSENEN	0.01	0.024	-10000	0	-0.58	1	1
KREMEN2	-0.038	0.15	-10000	0	-0.48	60	60
DKK1	-0.15	0.24	-10000	0	-0.51	185	185
beta catenin/beta TrCP1	0.05	0.068	0.25	2	-10000	0	2
APH1B	0.006	0.054	-10000	0	-0.58	5	5
APH1A	0.011	0	-10000	0	-10000	0	0
AXIN1	-0.013	0.047	-10000	0	-0.36	5	5
CtBP/CBP/TCF1/TLE1/AES	0.013	0.053	-10000	0	-0.43	4	4
PSEN1	0.011	0	-10000	0	-10000	0	0
FOS	-0.026	0.14	-10000	0	-0.53	41	41
JUN	0.007	0.052	-10000	0	-0.56	5	5
MAP3K7	0.01	0.002	-10000	0	-10000	0	0
CTNNB1	0.047	0.072	0.27	2	-10000	0	2
MAPK3	0.01	0.024	-10000	0	-0.58	1	1
DKK2/LRP6/Kremen 2	-0.069	0.16	-10000	0	-0.32	159	159
HNF1A	0.005	0.057	-10000	0	-0.56	6	6
CTBP1	0.01	0.024	-10000	0	-0.58	1	1
MYC	0.01	0.13	-10000	0	-1.4	5	5
NKD1	-0.13	0.24	-10000	0	-0.52	158	158
FZD1	0.009	0.039	-10000	0	-0.54	3	3
NOTCH1 precursor/Deltex homolog 1	0.006	0.097	-10000	0	-0.59	10	10
apoptosis	-0.061	0.13	-10000	0	-0.3	112	112
Delta 1/NOTCHprecursor	0.009	0.096	-10000	0	-0.63	10	10
DLL1	-0.003	0.086	-10000	0	-0.52	16	16
PPARD	0.019	0.058	-10000	0	-1.4	1	1
Gamma Secretase	0.031	0.033	-10000	0	-0.29	6	6
APC	-0.028	0.1	-10000	0	-0.47	24	24
DVL1	-0.01	0.053	-10000	0	-0.5	4	4
CSNK2A1	0.012	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.11	0.18	-10000	0	-0.32	225	225
LRP6	0.009	0.034	-10000	0	-0.58	2	2
CSNK1A1	0.01	0.034	-10000	0	-0.58	2	2
NLK	0.011	0.004	-10000	0	-10000	0	0
CCND1	0.019	0.058	-10000	0	-1.4	1	1
WNT1	-0.009	0.087	-10000	0	-0.46	21	21
Axin1/APC/beta catenin	0.025	0.079	-10000	0	-0.37	12	12
DKK2	-0.086	0.21	-10000	0	-0.54	106	106
NOTCH1 precursor/DVL1	-0.017	0.09	-10000	0	-0.66	10	10
GSK3B	0.009	0.034	-10000	0	-0.58	2	2
FRAT1	0.01	0.024	-10000	0	-0.58	1	1
NOTCH/Deltex homolog 1	-0.021	0.092	-10000	0	-0.6	10	10
PPP2R5D	0.059	0.12	0.25	154	-10000	0	154
MAPK1	0.01	0.024	-10000	0	-0.58	1	1
WNT1/LRP6/FZD1	-0.094	0.15	-10000	0	-0.34	89	89
RBPJ	0.01	0.031	-10000	0	-0.52	2	2
CREBBP	0.014	0.002	-10000	0	-10000	0	0

×

IL1-mediated signaling 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
UBC13/UEV1A	-0.036	0.12	-9999	-0.33	85	85
PRKCZ	0.01	0.031	-9999	-0.52	2	2
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.009	0.033	-9999	-0.46	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.013	0.081	-9999	-0.31	12	12
IRAK/TOLLIP	-0.015	0.096	-9999	-0.41	7	7
IKBKB	0.011	0.019	-9999	-0.46	1	1
IKBKG	0.01	0.024	-9999	-0.58	1	1
IL1 alpha/IL1R2	-0.1	0.2	-9999	-0.4	169	169
IL1A	-0.09	0.21	-9999	-0.51	115	115
IL1B	-0.056	0.17	-9999	-0.4	107	107
IRAK/TRAF6/p62/Atypical PKCs	0.002	0.096	-9999	-0.58	5	5
IL1R2	-0.055	0.18	-9999	-0.52	74	74
IL1R1	-0.005	0.092	-9999	-0.51	19	19
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.008	0.09	-9999	-0.36	10	10
TOLLIP	0.01	0.024	-9999	-0.58	1	1
TICAM2	-0.011	0.11	-9999	-0.58	21	21
MAP3K3	0.009	0.034	-9999	-0.58	2	2
TAK1/TAB1/TAB2	0.008	0	-9999	-10000	0	0
IKK complex/ELKS	0.02	0.087	-9999	-0.61	4	4
JUN	-0.002	0.089	-9999	-0.55	4	4
MAP3K7	0.011	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.031	0.14	-9999	-0.54	17	17
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.043	0.14	-9999	-0.34	69	69
PIK3R1	0.008	0.042	-9999	-0.58	3	3
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.034	0.13	-9999	-0.32	69	69
IL1 beta fragment/IL1R1/IL1RAP	-0.045	0.15	-9999	-0.37	73	73
NFKB1	0.01	0.024	-9999	-0.58	1	1
MAPK8	-0.006	0.089	-9999	-0.53	4	4
IRAK1	-0.024	0.1	-9999	-0.41	7	7
IL1RN/IL1R1	-0.04	0.14	-9999	-0.39	84	84
IRAK4	0.011	0	-9999	-10000	0	0
PRKCI	0.008	0.042	-9999	-0.58	3	3
TRAF6	0.01	0.024	-9999	-0.58	1	1
PI3K	0.013	0.04	-9999	-0.42	5	5
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.013	0.096	-9999	-0.39	11	11
CHUK	0.007	0.048	-9999	-0.58	4	4
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.045	0.15	-9999	-0.37	73	73
IL1 beta/IL1R2	-0.081	0.19	-9999	-0.46	88	88
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.018	0.082	-9999	-0.36	7	7
NF kappa B1 p50/RelA	-0.055	0.11	-9999	-0.49	18	18
IRAK3	-0.026	0.14	-9999	-0.54	41	41
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.04	0.15	-9999	-0.54	19	19
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.022	0.11	-9999	-0.5	6	6
IL1 alpha/IL1R1/IL1RAP	-0.056	0.15	-9999	-0.32	137	137
RELA	0.011	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.011	0	-9999	-10000	0	0
MYD88	0.011	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	-0.008	0.094	-9999	-0.36	9	9
IL1RAP	0.001	0.076	-9999	-0.58	10	10
UBE2N	0.01	0.024	-9999	-0.58	1	1
IRAK/TRAF6	-0.081	0.14	-9999	-0.46	41	41
CASP1	-0.021	0.13	-9999	-0.54	35	35
IL1RN/IL1R2	-0.074	0.19	-9999	-0.43	122	122
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.035	0.14	-9999	-0.34	73	73
TMEM189-UBE2V1	-0.062	0.16	-9999	-0.46	85	85
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.025	0.11	-9999	-0.4	21	21
PIK3CA	0.009	0.034	-9999	-0.58	2	2
IL1RN	-0.051	0.17	-9999	-0.52	70	70
TRAF6/TAK1/TAB1/TAB2	-0.031	0.079	-9999	-0.38	5	5
MAP2K6	-0.011	0.091	-9999	-0.33	15	15

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.025	0.26	-10000	0	-0.87	38	38
NCK1/PAK1/Dok-R	-0.038	0.11	-10000	0	-0.41	41	41
NCK1/Dok-R	-0.026	0.3	-10000	0	-1.1	38	38
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
mol:beta2-estradiol	0.006	0.057	0.24	30	-10000	0	30
RELA	0.011	0	-10000	0	-10000	0	0
SHC1	0.012	0.001	-10000	0	-10000	0	0
Rac/GDP	0.008	0	-10000	0	-10000	0	0
F2	-0.11	0.23	0.25	23	-0.5	142	165
TNIP2	0.01	0.024	-10000	0	-0.58	1	1
NF kappa B/RelA	-0.04	0.26	-10000	0	-0.99	37	37
FN1	-0.086	0.21	-10000	0	-0.52	109	109
PLD2	-0.007	0.3	-10000	0	-1.1	37	37
PTPN11	0.006	0.054	-10000	0	-0.58	5	5
GRB14	-0.12	0.24	-10000	0	-0.54	142	142
ELK1	0.005	0.27	-10000	0	-0.99	37	37
GRB7	0.002	0.066	-10000	0	-0.46	12	12
PAK1	0.011	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.085	0.3	-10000	0	-1.1	41	41
CDKN1A	0.041	0.2	-10000	0	-0.68	22	22
ITGA5	-0.005	0.09	-10000	0	-0.49	20	20
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.026	0.3	-10000	0	-1.1	38	38
CRK	0.011	0.019	-10000	0	-0.46	1	1
mol:NO	0.033	0.21	-10000	0	-0.64	41	41
PLG	-0.032	0.31	-10000	0	-1.1	38	38
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.02	0.24	-10000	0	-0.84	37	37
GRB2	0.011	0	-10000	0	-10000	0	0
PIK3R1	0.009	0.042	-10000	0	-0.58	3	3
ANGPT2	0.018	0.2	-10000	0	-0.72	16	16
BMX	-0.052	0.32	-10000	0	-1.1	39	39
ANGPT1	-0.018	0.31	-10000	0	-1.2	32	32
tube development	0.035	0.22	-10000	0	-0.68	34	34
ANGPT4	0.001	0.042	-10000	0	-0.45	5	5
response to hypoxia	-0.001	0.019	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.077	0.33	-10000	0	-1.2	37	37
alpha5/beta1 Integrin	0.005	0.065	-10000	0	-0.34	20	20
FGF2	-0.039	0.16	-10000	0	-0.52	56	56
STAT5A (dimer)	0.036	0.24	-10000	0	-0.81	25	25
mol:L-citrulline	0.033	0.21	-10000	0	-0.64	41	41
AGTR1	-0.093	0.21	-10000	0	-0.51	118	118
MAPK14	0.001	0.3	-10000	0	-1.1	37	37
Tie2/SHP2	-0.038	0.19	-10000	0	-1	17	17
TEK	-0.016	0.21	-10000	0	-1.3	13	13
RPS6KB1	0.024	0.25	-10000	0	-0.85	38	38
Angiotensin II/AT1	-0.066	0.15	-10000	0	-0.37	118	118
Tie2/Ang1/GRB2	-0.011	0.31	-10000	0	-1.2	37	37
MAPK3	0.001	0.28	-10000	0	-1	37	37
MAPK1	0.001	0.28	-10000	0	-1	37	37
Tie2/Ang1/GRB7	-0.015	0.31	-10000	0	-1.2	37	37
NFKB1	0.01	0.024	-10000	0	-0.58	1	1
MAPK8	-0.007	0.3	-10000	0	-1.1	37	37
PI3K	0.013	0.29	-10000	0	-1	38	38
FES	-0.005	0.31	-10000	0	-1.1	38	38
Crk/Dok-R	-0.026	0.29	-10000	0	-1.1	38	38
Tie2/Ang1/ABIN2	-0.011	0.31	-10000	0	-1.2	37	37
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.03	0.23	-10000	0	-0.77	38	38
STAT5A	0.012	0.001	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.026	0.25	-10000	0	-0.83	38	38
Tie2/Ang2	0.021	0.27	-10000	0	-0.91	34	34
Tie2/Ang1	-0.015	0.33	-10000	0	-1.2	37	37
FOXO1	0.032	0.24	-10000	0	-0.77	41	41
ELF1	0.013	0.046	-10000	0	-0.59	3	3
ELF2	-0.008	0.3	-10000	0	-1.1	37	37
mol:Choline	-0.003	0.29	-10000	0	-1.1	37	37
cell migration	-0.03	0.067	-10000	0	-0.23	42	42
FYN	0.03	0.24	-10000	0	-0.78	34	34
DOK2	-0.01	0.11	-10000	0	-0.55	23	23
negative regulation of cell cycle	0.044	0.19	-10000	0	-0.61	22	22
ETS1	-0.003	0.083	-10000	0	-0.43	13	13
PXN	0.037	0.21	-10000	0	-0.68	38	38
ITGB1	0.011	0	-10000	0	-10000	0	0
NOS3	0.028	0.23	-10000	0	-0.73	41	41
RAC1	0.011	0	-10000	0	-10000	0	0
TNF	-0.022	0.14	-10000	0	-0.53	34	34
MAPKKK cascade	-0.003	0.29	-10000	0	-1.1	37	37
RASA1	0.009	0.034	-10000	0	-0.58	2	2
Tie2/Ang1/Shc	-0.01	0.31	-10000	0	-1.2	37	37
NCK1	0.009	0.034	-10000	0	-0.58	2	2
vasculogenesis	0.036	0.19	-10000	0	-0.57	41	41
mol:Phosphatidic acid	-0.003	0.29	-10000	0	-1.1	37	37
mol:Angiotensin II	0.001	0.004	-10000	0	-10000	0	0
mol:NADP	0.033	0.21	-10000	0	-0.64	41	41
Rac1/GTP	-0.06	0.2	-10000	0	-0.78	38	38
MMP2	-0.028	0.32	-10000	0	-1.2	38	38

×

Arf6 signaling events

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
CENTA1/KIF3B	0.013	0.035	-9999	-0.44	3	3
ARNO/beta Arrestin1-2	-0.004	0.07	-9999	-10000	0	0
EGFR	0.004	0.063	-9999	-0.53	8	8
EPHA2	0.006	0.055	-9999	-0.54	6	6
USP6	0.008	0.041	-9999	-0.49	4	4
IQSEC1	0.011	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.13	0.19	-9999	-0.36	223	223
ARRB2	0.007	0.008	-9999	-10000	0	0
mol:GTP	0.004	0.046	-9999	-0.26	12	12
ARRB1	0.009	0.034	-9999	-0.58	2	2
FBXO8	0.009	0.034	-9999	-0.58	2	2
TSHR	-0.013	0.096	-9999	-0.46	26	26
EGF	-0.18	0.25	-9999	-0.51	216	216
somatostatin receptor activity	0	0	-9999	-0.001	38	38
ARAP2	-0.006	0.099	-9999	-0.58	17	17
mol:GDP	-0.033	0.086	-9999	-0.3	33	33
mol:PI-3-4-5-P3	0	0	-9999	-0.001	13	13
ITGA2B	-0.044	0.16	-9999	-0.5	63	63
ARF6	0.01	0.024	-9999	-0.58	1	1
Ephrin A1/EPHA2/NCK1/GIT1	0.024	0.045	-9999	-0.37	6	6
ADAP1	0.01	0.031	-9999	-0.52	2	2
KIF13B	0.009	0.034	-9999	-0.58	2	2
HGF/MET	-0.02	0.12	-9999	-0.39	54	54
PXN	0.011	0	-9999	-10000	0	0
ARF6/GTP	-0.038	0.093	-9999	-0.28	38	38
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.099	0.16	-9999	-0.3	223	223
ADRB2	-0.031	0.15	-9999	-0.54	45	45
receptor agonist activity	0	0	-9999	0	38	38
actin filament binding	0	0	-9999	-0.001	41	41
SRC	0.01	0.024	-9999	-0.58	1	1
ITGB3	-0.006	0.098	-9999	-0.54	19	19
GNAQ	0.005	0.059	-9999	-0.58	6	6
EFA6/PI-4-5-P2	0	0	-9999	-0.001	31	31
ARF6/GDP	-0.002	0.1	-9999	-0.35	34	34
ARF6/GDP/GULP/ACAP1	-0.06	0.14	-9999	-0.38	68	68
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.013	0.1	-9999	-0.32	38	38
ACAP1	-0.026	0.14	-9999	-0.54	40	40
ACAP2	0.001	0.076	-9999	-0.58	10	10
LHCGR/beta Arrestin2	0.001	0.012	-9999	-0.26	1	1
EFNA1	0.011	0.019	-9999	-0.46	1	1
HGF	-0.037	0.16	-9999	-0.54	52	52
CYTH3	0.007	0.029	-9999	-0.4	3	3
CYTH2	0.008	0.002	-9999	-10000	0	0
NCK1	0.009	0.034	-9999	-0.58	2	2
fibronectin binding	0	0	-9999	0	33	33
endosomal lumen acidification	0	0	-9999	0	32	32
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.051	0.18	-9999	-0.54	68	68
GNAQ/ARNO	0.01	0.031	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	17	17
MET	0.01	0.031	-9999	-0.52	2	2
GNA14	-0.007	0.1	-9999	-0.56	19	19
GNA15	-0.008	0.1	-9999	-0.54	21	21
GIT1	0.01	0.024	-9999	-0.58	1	1
mol:PI-4-5-P2	0	0	-9999	-0.001	35	35
GNA11	0.007	0.05	-9999	-0.53	5	5
LHCGR	0	0.019	-9999	-0.46	1	1
AGTR1	-0.094	0.21	-9999	-0.51	118	118
desensitization of G-protein coupled receptor protein signaling pathway	0.001	0.011	-9999	-0.26	1	1
IPCEF1/ARNO	-0.073	0.12	-9999	-0.47	1	1
alphaIIb/beta3 Integrin	-0.036	0.13	-9999	-0.37	81	81

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.012	0.045	-9999	-0.37	8	8
alphaV beta3 Integrin	-0.025	0.14	-9999	-0.36	74	74
PTK2	-0.026	0.15	-9999	-0.52	28	28
IGF1R	0.01	0.024	-9999	-0.58	1	1
PI4KB	0.011	0	-9999	-10000	0	0
MFGE8	0	0.074	-9999	-0.49	13	13
SRC	0.01	0.024	-9999	-0.58	1	1
CDKN1B	-0.035	0.13	-9999	-0.5	29	29
VEGFA	0.011	0.019	-9999	-0.46	1	1
ILK	-0.034	0.13	-9999	-0.49	28	28
ROCK1	0	0.08	-9999	-0.58	11	11
AKT1	-0.024	0.12	-9999	-0.45	29	29
PTK2B	0.011	0.08	-9999	-0.31	28	28
alphaV/beta3 Integrin/JAM-A	-0.041	0.15	-9999	-0.37	75	75
CBL	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.001	0.083	-9999	-0.34	32	32
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.028	0.13	-9999	-0.33	64	64
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.005	0.11	-9999	-0.64	10	10
alphaV/beta3 Integrin/Syndecan-1	0.005	0.082	-9999	-0.35	30	30
PI4KA	0.011	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.12	0.2	-9999	-0.58	68	68
PI4 Kinase	0.017	0	-9999	-10000	0	0
PIK3CA	0.009	0.034	-9999	-0.58	2	2
alphaV/beta3 Integrin/Osteopontin	-0.1	0.18	-9999	-0.32	212	212
RPS6KB1	-0.083	0.21	-9999	-0.54	71	71
TLN1	0.01	0.024	-9999	-0.58	1	1
MAPK3	-0.065	0.2	-9999	-0.66	48	48
GPR124	0.003	0.069	-9999	-0.55	9	9
MAPK1	-0.065	0.2	-9999	-0.64	52	52
PXN	0.011	0	-9999	-10000	0	0
PIK3R1	0.008	0.042	-9999	-0.58	3	3
alphaV/beta3 Integrin/Tumstatin	-0.047	0.14	-9999	-0.32	121	121
cell adhesion	0.002	0.092	-9999	-0.38	24	24
ANGPTL3	0.002	0.033	-9999	-0.46	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	0.018	0.041	-9999	-0.35	5	5
IGF-1R heterotetramer	0.01	0.024	-9999	-0.58	1	1
Rac1/GDP	0.008	0	-9999	-10000	0	0
TGFBR2	0.011	0.019	-9999	-0.46	1	1
ITGB3	-0.006	0.098	-9999	-0.54	19	19
IGF1	-0.073	0.2	-9999	-0.52	94	94
RAC1	0.011	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	0	0.097	-9999	-0.38	34	34
apoptosis	0	0.08	-9999	-0.58	11	11
CD47	0.009	0.034	-9999	-0.58	2	2
alphaV/beta3 Integrin/CD47	0.004	0.086	-9999	-0.36	30	30
VCL	0.009	0.034	-9999	-0.58	2	2
alphaV/beta3 Integrin/Del1	-0.025	0.15	-9999	-0.42	66	66
CSF1	0.006	0.055	-9999	-0.54	6	6
PIK3C2A	-0.053	0.18	-9999	-0.6	45	45
PI4 Kinase/Pyk2	-0.058	0.12	-9999	-0.46	24	24
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.009	0.083	-9999	-0.34	26	26
FAK1/Vinculin	-0.014	0.12	-9999	-0.42	27	27
alphaV beta3/Integrin/ppsTEM5	0	0.098	-9999	-0.38	34	34
RHOA	0.01	0.024	-9999	-0.58	1	1
VTN	-0.051	0.17	-9999	-0.5	71	71
BCAR1	0.008	0.044	-9999	-0.52	4	4
FGF2	-0.039	0.16	-9999	-0.52	56	56
F11R	-0.018	0.11	-9999	-0.37	56	56
alphaV/beta3 Integrin/Lactadherin	-0.001	0.096	-9999	-0.35	39	39
alphaV/beta3 Integrin/TGFBR2	0.005	0.082	-9999	-0.37	23	23
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.018	0.065	-9999	-0.34	17	17
HSP90AA1	0.01	0.024	-9999	-0.58	1	1
alphaV/beta3 Integrin/Talin	0.005	0.075	-9999	-0.32	30	30
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.086	0.21	-9999	-0.52	109	109
alphaV/beta3 Integrin/Pyk2	0.013	0.081	-9999	-0.31	28	28
SDC1	0.01	0.024	-9999	-0.58	1	1
VAV3	-0.021	0.12	-9999	-0.61	4	4
PTPN11	0.006	0.054	-9999	-0.58	5	5
IRS1	0.002	0.072	-9999	-0.58	9	9
FAK1/Paxillin	-0.014	0.12	-9999	-0.4	28	28
cell migration	-0.006	0.11	-9999	-0.39	22	22
ITGAV	0	0.08	-9999	-0.58	11	11
PI3K	-0.061	0.13	-9999	-0.5	25	25
SPP1	-0.16	0.25	-9999	-0.52	194	194
KDR	0.005	0.058	-9999	-0.53	7	7
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0	0.08	-9999	-0.58	11	11
COL4A3	-0.073	0.19	-9999	-0.51	95	95
angiogenesis	-0.065	0.2	-9999	-0.66	48	48
Rac1/GTP	-0.014	0.12	-9999	-0.56	4	4
EDIL3	-0.039	0.16	-9999	-0.57	51	51
cell proliferation	0.005	0.081	-9999	-0.37	23	23

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.011	0	-9999	-10000	0	0
ITGB7	-0.014	0.12	-9999	-0.53	28	28
ITGA4	-0.018	0.13	-9999	-0.56	30	30
alpha4/beta7 Integrin	-0.022	0.13	-9999	-0.43	52	52
alpha4/beta1 Integrin	-0.004	0.093	-9999	-0.41	30	30

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.004	0.092	-10000	0	-0.54	17	17
Jak2/Leptin Receptor	-0.055	0.13	0.19	2	-0.43	43	45
PTP1B/AKT1	-0.021	0.078	-10000	0	-0.3	18	18
FYN	0.005	0.06	-10000	0	-0.55	7	7
p210 bcr-abl/PTP1B	-0.029	0.083	-10000	0	-0.29	25	25
EGFR	0.001	0.064	-10000	0	-0.54	8	8
EGF/EGFR	-0.097	0.15	-10000	0	-0.34	113	113
CSF1	0.006	0.055	-10000	0	-0.54	6	6
AKT1	0.01	0.025	-10000	0	-0.59	1	1
INSR	0.009	0.034	-10000	0	-0.58	2	2
PTP1B/N-cadherin	-0.07	0.15	-10000	0	-0.35	103	103
Insulin Receptor/Insulin	-0.026	0.061	-10000	0	-0.34	10	10
HCK	-0.018	0.12	-10000	0	-0.55	31	31
CRK	0.011	0.019	-10000	0	-0.46	1	1
TYK2	-0.022	0.082	-10000	0	-0.32	17	17
EGF	-0.18	0.25	-10000	0	-0.51	216	216
YES1	0.004	0.064	-10000	0	-0.58	7	7
CAV1	-0.042	0.1	-10000	0	-0.36	21	21
TXN	0.009	0.004	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.02	0.086	-10000	0	-0.34	17	17
cell migration	0.029	0.083	0.29	25	-10000	0	25
STAT3	0.011	0.001	-10000	0	-10000	0	0
PRLR	-0.042	0.17	-10000	0	-0.58	54	54
ITGA2B	-0.044	0.16	-10000	0	-0.5	63	63
CSF1R	-0.03	0.14	-10000	0	-0.53	45	45
Prolactin Receptor/Prolactin	-0.043	0.14	-10000	0	-0.42	71	71
FGR	-0.026	0.14	-10000	0	-0.54	40	40
PTP1B/p130 Cas	-0.024	0.085	-10000	0	-0.32	21	21
Crk/p130 Cas	-0.017	0.084	-10000	0	-0.34	17	17
DOK1	-0.018	0.089	-10000	0	-0.37	20	20
JAK2	-0.047	0.13	-10000	0	-0.41	49	49
Jak2/Leptin Receptor/Leptin	-0.055	0.12	-10000	0	-0.45	29	29
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
PTPN1	-0.029	0.084	-10000	0	-0.3	25	25
LYN	0.011	0	-10000	0	-10000	0	0
CDH2	-0.084	0.21	-10000	0	-0.53	104	104
SRC	0	0.059	-10000	0	-1.2	1	1
ITGB3	-0.007	0.098	-10000	0	-0.54	19	19
CAT1/PTP1B	-0.081	0.17	-10000	0	-0.47	60	60
CAPN1	0.01	0.025	-10000	0	-0.59	1	1
CSK	0.01	0.024	-10000	0	-0.58	1	1
PI3K	-0.022	0.066	-10000	0	-0.44	7	7
mol:H2O2	-0.001	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.05	0.11	-10000	0	-0.44	27	27
negative regulation of transcription	-0.046	0.13	-10000	0	-0.41	49	49
FCGR2A	-0.022	0.13	-10000	0	-0.54	36	36
FER	0	0.071	-10000	0	-0.54	10	10
alphaIIb/beta3 Integrin	-0.038	0.13	-10000	0	-0.37	81	81
BLK	-0.12	0.23	-10000	0	-0.52	139	139
Insulin Receptor/Insulin/Shc	0.013	0.031	-10000	0	-0.36	3	3
RHOA	0.01	0.025	-10000	0	-0.59	1	1
LEPR	0	0.079	-10000	0	-0.55	12	12
BCAR1	0.008	0.044	-10000	0	-0.52	4	4
p210 bcr-abl/Grb2	0.011	0	-10000	0	-10000	0	0
mol:NADPH	-0.002	0.003	-10000	0	-10000	0	0
TRPV6	-0.083	0.19	-10000	0	-0.51	66	66
PRL	-0.013	0.089	-10000	0	-0.45	23	23
SOCS3	-0.003	0.13	-10000	0	-1.3	5	5
SPRY2	0.007	0.043	-10000	0	-0.59	3	3
Insulin Receptor/Insulin/IRS1	0.007	0.058	-10000	0	-0.38	12	12
CSF1/CSF1R	-0.038	0.12	-10000	0	-0.42	38	38
Ras protein signal transduction	0.021	0.025	-10000	0	-10000	0	0
IRS1	0.002	0.072	-10000	0	-0.58	9	9
INS	-0.002	0.036	-10000	0	-0.5	3	3
LEP	-0.024	0.12	-10000	0	-0.46	39	39
STAT5B	-0.033	0.09	-10000	0	-0.29	34	34
STAT5A	-0.033	0.09	-10000	0	-0.29	34	34
GRB2	0.011	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.03	0.1	-10000	0	-0.4	28	28
CSN2	-0.008	0.06	-10000	0	-10000	0	0
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
LAT	-0.033	0.14	-10000	0	-0.57	32	32
YBX1	0.016	0.016	-10000	0	-0.36	1	1
LCK	-0.031	0.14	-10000	0	-0.51	48	48
SHC1	0.011	0	-10000	0	-10000	0	0
NOX4	-0.073	0.19	-10000	0	-0.52	92	92

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.011	0.058	0.26	16	-0.3	4	20
RFC1	0.011	0.062	0.24	22	-0.38	4	26
PRKDC	0.01	0.061	0.24	22	-0.3	6	28
RIPK1	0.013	0.003	-10000	0	-10000	0	0
CASP7	-0.01	0.051	0.24	6	-0.43	1	7
FASLG/FAS/FADD/FAF1	0.004	0.11	0.22	61	-0.3	31	92
MAP2K4	-0.027	0.13	-10000	0	-0.43	23	23
mol:ceramide	-0.027	0.12	-10000	0	-0.39	44	44
GSN	0.006	0.068	0.26	16	-0.29	12	28
FASLG/FAS/FADD/FAF1/Caspase 8	0.001	0.12	-10000	0	-0.36	33	33
FAS	-0.001	0.074	-10000	0	-0.56	10	10
BID	0.008	0.05	0.29	13	-0.32	2	15
MAP3K1	-0.006	0.088	0.22	5	-0.31	12	17
MAP3K7	0.01	0.004	-10000	0	-10000	0	0
RB1	0	0.085	0.26	15	-0.35	21	36
CFLAR	0.013	0.003	-10000	0	-10000	0	0
HGF/MET	-0.066	0.17	-10000	0	-0.37	136	136
ARHGDIB	0.009	0.06	0.26	15	-0.33	4	19
FADD	0.009	0.006	-10000	0	-10000	0	0
actin filament polymerization	-0.006	0.068	0.29	12	-0.26	16	28
NFKB1	-0.043	0.085	-10000	0	-0.73	2	2
MAPK8	-0.045	0.17	-10000	0	-0.45	69	69
DFFA	0.012	0.056	0.26	16	-0.28	3	19
DNA fragmentation during apoptosis	0.012	0.056	0.26	16	-0.28	3	19
FAS/FADD/MET	0.012	0.052	-10000	0	-0.34	11	11
CFLAR/RIP1	0.013	0.007	-10000	0	-10000	0	0
FAIM3	-0.012	0.11	-10000	0	-0.52	27	27
FAF1	0.009	0.008	-10000	0	-10000	0	0
PARP1	0.012	0.056	0.24	22	-0.28	3	25
DFFB	0.012	0.056	0.26	16	-0.28	3	19
CHUK	-0.04	0.08	-10000	0	-0.49	5	5
FASLG	-0.055	0.18	-10000	0	-0.53	69	69
FAS/FADD	0.006	0.055	-10000	0	-0.41	10	10
HGF	-0.037	0.16	-10000	0	-0.54	52	52
LMNA	0.009	0.052	0.23	14	-0.3	3	17
CASP6	0.011	0.054	0.25	15	-0.28	3	18
CASP10	0.008	0.025	-10000	0	-0.58	1	1
CASP3	0.014	0.067	0.28	27	-0.33	3	30
PTPN13	-0.082	0.21	-10000	0	-0.56	98	98
CASP8	0.013	0.067	0.3	27	-0.44	1	28
IL6	-0.16	0.41	-10000	0	-1.2	72	72
MET	0.01	0.031	-10000	0	-0.52	2	2
ICAD/CAD	0.011	0.052	0.24	16	-0.29	2	18
FASLG/FAS/FADD/FAF1/Caspase 10	-0.027	0.12	-10000	0	-0.39	44	44
activation of caspase activity by cytochrome c	0.008	0.05	0.29	13	-0.32	2	15
PAK2	0.011	0.06	0.26	16	-0.39	3	19
BCL2	-0.007	0.1	-10000	0	-0.55	20	20

×

Retinoic acid receptors-mediated 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
HDAC1	0.011	0	-10000	0	-10000	0	0
HDAC3	0.011	0	-10000	0	-10000	0	0
VDR	0.01	0.024	-10000	0	-0.58	1	1
Cbp/p300/PCAF	0.01	0.072	-10000	0	-0.37	20	20
EP300	0.007	0.048	-10000	0	-0.58	4	4
RARs/AIB1/Cbp/p300/PCAF/9cRA	-0.002	0.079	-10000	0	-0.34	16	16
KAT2B	-0.006	0.099	-10000	0	-0.58	17	17
MAPK14	0.011	0	-10000	0	-10000	0	0
AKT1	0.005	0.085	0.21	12	-0.3	15	27
RAR alpha/9cRA/Cyclin H	-0.046	0.083	-10000	0	-0.5	4	4
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.006	0.085	-10000	0	-0.38	17	17
CDC2	0	0.002	-10000	0	-10000	0	0
response to UV	0.001	0.003	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.031	0.081	-10000	0	-0.47	1	1
NCOR2	0.008	0.046	-10000	0	-0.55	4	4
VDR/VDR/Vit D3	0.008	0.018	-10000	0	-0.43	1	1
RXRs/RARs/NRIP1/9cRA	-0.049	0.17	-10000	0	-0.43	77	77
NCOA2	0.004	0.067	-10000	0	-0.56	8	8
NCOA3	0.01	0.024	-10000	0	-0.58	1	1
NCOA1	0.01	0.024	-10000	0	-0.58	1	1
VDR/VDR/DNA	0.01	0.024	-10000	0	-0.58	1	1
RARG	0.006	0.059	-10000	0	-0.58	6	6
RAR gamma1/9cRA	0.012	0.038	-10000	0	-0.36	6	6
MAPK3	0.011	0.024	-10000	0	-0.58	1	1
MAPK1	0.01	0.024	-10000	0	-0.58	1	1
MAPK8	0.011	0.024	-10000	0	-0.58	1	1
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.058	0.16	-10000	0	-0.43	82	82
RARA	-0.039	0.1	-10000	0	-0.25	82	82
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.009	0.094	-10000	0	-0.4	19	19
PRKCA	0.011	0.031	-10000	0	-0.52	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.058	0.17	-10000	0	-0.43	87	87
RXRG	-0.071	0.14	-10000	0	-0.34	83	83
RXRA	-0.028	0.091	-10000	0	-0.26	5	5
RXRB	-0.061	0.13	-10000	0	-0.34	81	81
VDR/Vit D3/DNA	0.008	0.018	-10000	0	-0.43	1	1
RBP1	-0.085	0.2	-10000	0	-0.48	115	115
CRBP1/9-cic-RA	-0.061	0.14	-10000	0	-0.35	115	115
RARB	-0.004	0.095	-10000	0	-0.54	18	18
PRKCG	-0.15	0.24	-10000	0	-0.51	182	182
MNAT1	0.008	0.046	-10000	0	-0.55	4	4
RAR alpha/RXRs	-0.042	0.18	-10000	0	-0.44	70	70
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.04	0.15	-10000	0	-0.38	72	72
proteasomal ubiquitin-dependent protein catabolic process	-0.017	0.095	-10000	0	-0.36	18	18
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.058	0.17	-10000	0	-0.43	87	87
positive regulation of DNA binding	-0.044	0.079	-10000	0	-0.47	4	4
NRIP1	-0.06	0.2	-10000	0	-1.1	11	11
RXRs/RARs	-0.06	0.16	-10000	0	-0.42	89	89
RXRs/RXRs/DNA/9cRA	-0.066	0.17	-10000	0	-0.45	81	81
PRKACA	0.011	0	-10000	0	-10000	0	0
CDK7	0.008	0.042	-10000	0	-0.58	3	3
TFIIH	0.019	0.044	-10000	0	-0.39	6	6
RAR alpha/9cRA	-0.033	0.061	-10000	0	-0.39	4	4
CCNH	0.011	0	-10000	0	-10000	0	0
CREBBP	0.011	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	-0.006	0.042	-10000	0	-0.55	1	1

×

Ras signaling in the CD4+ TCR 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
ERK1-2/ELK1	-0.022	0.17	-9999	-0.52	45	45
MAP3K8	0.009	0.031	-9999	-0.52	2	2
FOS	-0.023	0.16	-9999	-0.59	30	30
PRKCA	0.01	0.031	-9999	-0.52	2	2
PTPN7	-0.048	0.17	-9999	-0.5	71	71
HRAS	0.008	0.041	-9999	-0.49	4	4
PRKCB	-0.04	0.16	-9999	-0.54	56	56
NRAS	0.001	0.076	-9999	-0.58	10	10
RAS family/GTP	0.011	0.069	-9999	-0.41	13	13
MAPK3	-0.02	0.14	-9999	-0.63	23	23
MAP2K1	-0.007	0.12	-9999	-0.42	40	40
ELK1	0.01	0.025	-9999	-0.58	1	1
BRAF	-0.013	0.12	-9999	-0.43	40	40
mol:GTP	0	0.001	-9999	-0.005	40	40
MAPK1	-0.02	0.14	-9999	-0.55	29	29
RAF1	-0.012	0.11	-9999	-0.42	39	39
KRAS	0.006	0.057	-9999	-0.56	6	6

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.059	0.15	-10000	0	-0.33	128	128
cell-cell adhesion	0.06	0.1	0.42	15	-10000	0	15
Ephrin B/EPHB2/RasGAP	0.008	0.089	-10000	0	-0.32	30	30
ITSN1	0.01	0.024	-10000	0	-0.58	1	1
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
SHC1	0.011	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.004	0.082	-10000	0	-0.34	32	32
Ephrin B1/EPHB1	-0.057	0.13	-10000	0	-0.29	139	139
HRAS/GDP	-0.058	0.1	-10000	0	-0.43	13	13
Ephrin B/EPHB1/GRB7	-0.051	0.14	-10000	0	-0.34	65	65
Endophilin/SYNJ1	0.006	0.083	-10000	0	-0.3	30	30
KRAS	0.006	0.057	-10000	0	-0.56	6	6
Ephrin B/EPHB1/Src	-0.047	0.14	-10000	0	-0.33	60	60
endothelial cell migration	0.021	0.038	-10000	0	-0.36	5	5
GRB2	0.011	0	-10000	0	-10000	0	0
GRB7	0.002	0.066	-10000	0	-0.46	12	12
PAK1	0.01	0.093	-10000	0	-0.6	5	5
HRAS	0.008	0.041	-10000	0	-0.49	4	4
RRAS	0.006	0.087	-10000	0	-0.32	28	28
DNM1	-0.006	0.093	-10000	0	-0.5	20	20
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.046	0.13	-10000	0	-0.31	60	60
lamellipodium assembly	-0.06	0.1	-10000	0	-0.42	15	15
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.023	0.1	-10000	0	-0.28	45	45
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
EPHB2	0	0.079	-10000	0	-0.55	12	12
EPHB3	-0.018	0.13	-10000	0	-0.54	32	32
EPHB1	-0.1	0.21	-10000	0	-0.49	138	138
EPHB4	0.011	0	-10000	0	-10000	0	0
mol:GDP	-0.024	0.11	-10000	0	-0.36	23	23
Ephrin B/EPHB2	0.002	0.087	-10000	0	-0.33	28	28
Ephrin B/EPHB3	-0.008	0.1	-10000	0	-0.34	39	39
JNK cascade	-0.037	0.12	-10000	0	-0.53	3	3
Ephrin B/EPHB1	-0.053	0.13	-10000	0	-0.34	60	60
RAP1/GDP	-0.011	0.1	-10000	0	-0.41	8	8
EFNB2	0.01	0.031	-10000	0	-0.52	2	2
EFNB3	-0.021	0.13	-10000	0	-0.52	36	36
EFNB1	0.01	0.024	-10000	0	-0.58	1	1
Ephrin B2/EPHB1-2	-0.051	0.13	-10000	0	-0.33	50	50
RAP1B	0.011	0	-10000	0	-10000	0	0
RAP1A	0.01	0.024	-10000	0	-0.58	1	1
CDC42/GTP	-0.065	0.12	-10000	0	-0.47	19	19
Rap1/GTP	-0.061	0.1	-10000	0	-0.43	17	17
axon guidance	-0.058	0.14	-10000	0	-0.33	128	128
MAPK3	-0.011	0.093	-10000	0	-0.39	9	9
MAPK1	-0.011	0.094	-10000	0	-0.38	11	11
Rac1/GDP	-0.016	0.11	-10000	0	-0.38	12	12
actin cytoskeleton reorganization	-0.053	0.091	-10000	0	-0.39	18	18
CDC42/GDP	-0.018	0.11	-10000	0	-0.39	15	15
PI3K	0.023	0.038	-10000	0	-0.36	5	5
EFNA5	-0.097	0.22	-10000	0	-0.52	122	122
Ephrin B2/EPHB4	0.014	0.019	-10000	0	-0.31	2	2
Ephrin B/EPHB2/Intersectin/N-WASP	0.011	0.073	-10000	0	-0.48	4	4
CDC42	0.006	0.054	-10000	0	-0.58	5	5
RAS family/GTP	-0.066	0.12	-10000	0	-0.46	23	23
PTK2	0.016	0.038	-10000	0	-0.57	1	1
MAP4K4	-0.037	0.12	-10000	0	-0.54	3	3
SRC	0.01	0.024	-10000	0	-0.58	1	1
KALRN	0.006	0.054	-10000	0	-0.58	5	5
Intersectin/N-WASP	0.016	0.018	-10000	0	-0.42	1	1
neuron projection morphogenesis	-0.009	0.11	-10000	0	-0.41	14	14
MAP2K1	-0.017	0.097	-10000	0	-0.4	10	10
WASL	0.011	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.044	0.13	-10000	0	-0.33	50	50
cell migration	-0.014	0.11	-10000	0	-0.44	10	10
NRAS	0.001	0.076	-10000	0	-0.58	10	10
SYNJ1	0.006	0.084	-10000	0	-0.3	30	30
PXN	0.011	0	-10000	0	-10000	0	0
TF	-0.046	0.13	-10000	0	-0.44	20	20
HRAS/GTP	-0.067	0.11	-10000	0	-0.47	17	17
Ephrin B1/EPHB1-2	-0.05	0.13	-10000	0	-0.27	148	148
cell adhesion mediated by integrin	0.011	0.081	0.32	24	-10000	0	24
RAC1	0.011	0	-10000	0	-10000	0	0
mol:GTP	-0.045	0.13	-10000	0	-0.49	15	15
RAC1-CDC42/GTP	-0.073	0.12	-10000	0	-0.47	29	29
RASA1	0.009	0.034	-10000	0	-0.58	2	2
RAC1-CDC42/GDP	-0.013	0.11	-10000	0	-0.41	10	10
ruffle organization	-0.026	0.12	-10000	0	-0.43	16	16
NCK1	0.009	0.034	-10000	0	-0.58	2	2
receptor internalization	0.003	0.095	-10000	0	-0.5	7	7
Ephrin B/EPHB2/KALRN	0.006	0.098	-10000	0	-0.35	30	30
ROCK1	-0.003	0.093	-10000	0	-0.34	39	39
RAS family/GDP	-0.048	0.088	-10000	0	-0.4	16	16
Rac1/GTP	-0.063	0.11	-10000	0	-0.45	15	15
Ephrin B/EPHB1/Src/Paxillin	-0.028	0.1	-10000	0	-0.28	60	60

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.044	0.14	-10000	0	-0.42	61	61
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.024	0.12	0.52	12	-10000	0	12
IL27/IL27R/JAK1	-0.024	0.16	-10000	0	-0.9	6	6
TBX21	-0.046	0.23	-10000	0	-0.59	59	59
IL12B	-0.004	0.071	-10000	0	-0.46	14	14
IL12A	-0.025	0.11	-10000	0	-0.41	47	47
IL6ST	-0.005	0.096	-10000	0	-0.58	16	16
IL27RA/JAK1	0.006	0.095	-10000	0	-1.2	3	3
IL27	-0.006	0.081	-10000	0	-0.46	18	18
TYK2	0.01	0.025	-10000	0	-0.58	1	1
T-helper cell lineage commitment	-0.19	0.4	-10000	0	-1.2	62	62
T-helper 2 cell differentiation	0.024	0.12	0.52	12	-10000	0	12
T cell proliferation during immune response	0.024	0.12	0.52	12	-10000	0	12
MAPKKK cascade	-0.024	0.12	-10000	0	-0.52	12	12
STAT3	0.011	0	-10000	0	-10000	0	0
STAT2	0.011	0.019	-10000	0	-0.46	1	1
STAT1	0.006	0.051	-10000	0	-0.5	6	6
IL12RB1	-0.034	0.15	-10000	0	-0.54	48	48
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.041	0.22	-10000	0	-0.6	47	47
IL27/IL27R/JAK2/TYK2	-0.024	0.13	-10000	0	-0.53	12	12
positive regulation of T cell mediated cytotoxicity	-0.024	0.12	-10000	0	-0.52	12	12
STAT1 (dimer)	-0.056	0.24	0.49	2	-0.78	29	31
JAK2	-0.008	0.1	-10000	0	-0.55	21	21
JAK1	0.009	0.042	-10000	0	-0.58	3	3
STAT2 (dimer)	-0.018	0.12	-10000	0	-0.51	12	12
T cell proliferation	-0.098	0.18	-10000	0	-0.5	52	52
IL12/IL12R/TYK2/JAK2	-0.043	0.14	-10000	0	-0.55	15	15
IL17A	-0.19	0.4	-10000	0	-1.3	62	62
mast cell activation	0.024	0.12	0.52	12	-10000	0	12
IFNG	-0.011	0.042	-10000	0	-0.12	48	48
T cell differentiation	-0.004	0.007	0.014	1	-0.022	58	59
STAT3 (dimer)	-0.018	0.12	-10000	0	-0.51	11	11
STAT5A (dimer)	-0.018	0.12	-10000	0	-0.51	11	11
STAT4 (dimer)	-0.037	0.16	-10000	0	-0.52	34	34
STAT4	-0.027	0.14	-10000	0	-0.56	40	40
T cell activation	-0.006	0.01	0.12	3	-10000	0	3
IL27R/JAK2/TYK2	-0.013	0.12	-10000	0	-0.88	6	6
GATA3	-0.026	0.22	-10000	0	-1.3	16	16
IL18	0.003	0.05	-10000	0	-0.39	9	9
positive regulation of mast cell cytokine production	-0.017	0.12	-10000	0	-0.5	11	11
IL27/EBI3	-0.026	0.13	-10000	0	-0.39	60	60
IL27RA	-0.002	0.096	-10000	0	-1.3	3	3
IL6	-0.15	0.25	-10000	0	-0.53	169	169
STAT5A	0.011	0	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.002	-10000	0	-10000	0	0
IL2	0.005	0.039	0.47	3	-10000	0	3
IL1B	-0.043	0.13	-10000	0	-0.38	80	80
EBI3	-0.031	0.15	-10000	0	-0.56	44	44
TNF	-0.012	0.09	-10000	0	-0.4	30	30

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.011	0	-9999	-10000	0	0
VLDLR	-0.041	0.16	-9999	-0.54	56	56
LRPAP1	0.01	0.024	-9999	-0.58	1	1
NUDC	0.011	0.019	-9999	-0.46	1	1
RELN/LRP8	-0.045	0.14	-9999	-0.31	122	122
CaM/Ca2+	0.008	0	-9999	-10000	0	0
KATNA1	0.01	0.024	-9999	-0.58	1	1
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.035	0.12	-9999	-0.32	63	63
IQGAP1/CaM	0.015	0.029	-9999	-0.39	3	3
DAB1	-0.079	0.2	-9999	-0.51	101	101
IQGAP1	0.009	0.039	-9999	-0.54	3	3
PLA2G7	-0.022	0.14	-9999	-0.56	35	35
CALM1	0.011	0	-9999	-10000	0	0
DYNLT1	0.011	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.014	0.036	-9999	-0.42	4	4
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.009	0.034	-9999	-0.58	2	2
CDK5R1	0.009	0.033	-9999	-0.46	3	3
LIS1/Poliovirus Protein 3A	0.014	0	-9999	-10000	0	0
CDK5R2	-0.05	0.16	-9999	-0.5	69	69
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.13	0.21	-9999	-0.37	229	229
YWHAE	0.011	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.025	0.12	-9999	-0.42	15	15
MAP1B	-0.012	0.052	-9999	-0.31	11	11
RAC1	0.017	0.012	-9999	-10000	0	0
p35/CDK5	-0.02	0.11	-9999	-0.48	3	3
RELN	-0.094	0.21	-9999	-0.52	118	118
PAFAH/LIS1	0.001	0.085	-9999	-0.35	29	29
LIS1/CLIP170	0.021	0.022	-9999	-0.35	2	2
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.045	0.081	-9999	-0.36	9	9
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.072	0.16	-9999	-0.4	61	61
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.033	0.13	-9999	-0.4	23	23
LIS1/IQGAP1	0.02	0.025	-9999	-0.35	2	2
RHOA	0.016	0.035	-9999	-0.81	1	1
PAFAH1B1	0.018	0	-9999	-10000	0	0
PAFAH1B3	0.008	0.044	-9999	-0.52	4	4
PAFAH1B2	0.007	0.048	-9999	-0.58	4	4
MAP1B/LIS1/Dynein heavy chain	0.012	0.036	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.02	0.12	-9999	-0.4	16	16
LRP8	0.008	0.042	-9999	-0.58	3	3
NDEL1/Katanin 60	-0.026	0.12	-9999	-0.42	16	16
P39/CDK5	-0.05	0.14	-9999	-0.48	23	23
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.022	0.012	-9999	-0.26	1	1
CDK5	-0.027	0.12	-9999	-0.29	63	63
PPP2R5D	0.011	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.018	0.019	-9999	-0.3	2	2
CSNK2A1	0.011	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.098	0.18	-9999	-0.37	138	138
RELN/VLDLR	-0.063	0.16	-9999	-0.35	96	96
CDC42	0.013	0.057	-9999	-0.58	5	5

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.011	0.04	-9999	-0.31	9	9
ADCY5	-0.058	0.14	-9999	-0.32	132	132
ADCY6	0.015	0	-9999	-10000	0	0
ADCY7	0.014	0.022	-9999	-0.3	3	3
ADCY1	-0.018	0.095	-9999	-0.28	66	66
ADCY2	-0.017	0.1	-9999	-0.34	54	54
ADCY3	0.015	0.015	-9999	-0.36	1	1
ADCY8	0.003	0.042	-9999	-0.27	14	14
PRKCE	0.009	0	-9999	-10000	0	0
ADCY9	0.014	0.025	-9999	-0.33	3	3
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.014	0.067	-9999	-0.34	5	5

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	-0.008	0.12	-9999	-0.42	38	38
CRKL	0.011	0	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
DOCK1	0.01	0.024	-9999	-0.58	1	1
ITGA4	-0.018	0.13	-9999	-0.56	30	30
alpha4/beta7 Integrin/MAdCAM1	-0.078	0.17	-9999	-0.36	112	112
EPO	0	0.053	-9999	-0.46	8	8
alpha4/beta7 Integrin	-0.022	0.13	-9999	-0.43	52	52
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.011	0.019	-9999	-0.46	1	1
alpha4/beta1 Integrin	-0.004	0.093	-9999	-0.41	30	30
EPO/EPOR (dimer)	0.003	0.061	-9999	-0.36	16	16
lamellipodium assembly	0.026	0.05	-9999	-0.44	5	5
PIK3CA	0.009	0.034	-9999	-0.58	2	2
PI3K	0.013	0.04	-9999	-0.42	5	5
ARF6	0.01	0.024	-9999	-0.58	1	1
JAK2	-0.006	0.11	-9999	-0.36	41	41
PXN	0.011	0	-9999	-10000	0	0
PIK3R1	0.008	0.042	-9999	-0.58	3	3
MADCAM1	-0.12	0.23	-9999	-0.52	151	151
cell adhesion	-0.078	0.17	-9999	-0.36	112	112
CRKL/CBL	0.017	0	-9999	-10000	0	0
ITGB1	0.011	0	-9999	-10000	0	0
SRC	-0.007	0.12	-9999	-0.42	39	39
ITGB7	-0.014	0.12	-9999	-0.53	28	28
RAC1	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.014	0.13	-9999	-0.43	49	49
p130Cas/Crk/Dock1	0.01	0.11	-9999	-0.51	18	18
VCAM1	-0.02	0.13	-9999	-0.53	35	35
RHOA	0.01	0.024	-9999	-0.58	1	1
alpha4/beta1 Integrin/Paxillin/GIT1	0.012	0.075	-9999	-0.32	27	27
BCAR1	-0.003	0.12	-9999	-0.4	40	40
EPOR	0.004	0.063	-9999	-0.5	9	9
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.011	0	-9999	-10000	0	0
GIT1	0.01	0.024	-9999	-0.58	1	1
Rac1/GTP	-0.002	0.051	-9999	-0.46	5	5

×

IL6-mediated signaling events

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
BCL2L1	-0.02	0.2	-10000	0	-0.71	13	13
CRP	-0.028	0.2	-10000	0	-0.73	14	14
cell cycle arrest	-0.034	0.22	-10000	0	-0.74	21	21
TIMP1	-0.009	0.18	-10000	0	-0.63	11	11
IL6ST	-0.002	0.096	-10000	0	-0.58	16	16
Rac1/GDP	-0.039	0.17	-10000	0	-0.51	43	43
AP1	0.002	0.12	-10000	0	-0.59	8	8
GAB2	0.01	0.034	-10000	0	-0.58	2	2
TNFSF11	-0.075	0.33	-10000	0	-1	53	53
HSP90B1	0.009	0.14	-10000	0	-1.3	6	6
GAB1	0.012	0.001	-10000	0	-10000	0	0
MAPK14	-0.03	0.16	-10000	0	-0.55	30	30
AKT1	0.037	0.072	-10000	0	-0.73	4	4
FOXO1	0.041	0.07	-10000	0	-0.68	4	4
MAP2K6	-0.036	0.16	-10000	0	-0.49	39	39
mol:GTP	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.03	0.18	-10000	0	-0.56	33	33
MITF	-0.048	0.17	-10000	0	-0.49	48	48
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.01	0.024	-10000	0	-0.58	1	1
A2M	0.009	0.09	-10000	0	-0.58	9	9
CEBPB	0.013	0.042	-10000	0	-0.48	4	4
GRB2/SOS1/GAB family/SHP2	0	0.089	0.22	1	-0.61	5	6
STAT3	-0.038	0.23	-10000	0	-0.78	22	22
STAT1	-0.009	0.068	-10000	0	-1.1	2	2
CEBPD	-0.022	0.2	-10000	0	-0.82	11	11
PIK3CA	0.011	0.034	-10000	0	-0.58	2	2
PI3K	0.016	0.04	-10000	0	-0.42	5	5
JUN	0.006	0.052	-10000	0	-0.56	5	5
PIAS3/MITF	-0.041	0.17	-10000	0	-0.51	38	38
MAPK11	-0.037	0.17	-10000	0	-0.57	35	35
STAT3 (dimer)/FOXO1	0.011	0.19	-10000	0	-0.65	12	12
GRB2/SOS1/GAB family	-0.059	0.13	-10000	0	-0.55	27	27
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.047	0.17	-10000	0	-0.47	53	53
GRB2	0.012	0.001	-10000	0	-10000	0	0
JAK2	-0.008	0.1	-10000	0	-0.55	21	21
LBP	-0.091	0.31	-10000	0	-0.87	61	61
PIK3R1	0.009	0.042	-10000	0	-0.58	3	3
JAK1	0.01	0.042	-10000	0	-0.58	3	3
MYC	-0.025	0.21	-10000	0	-0.87	14	14
FGG	-0.036	0.22	-10000	0	-0.77	15	15
macrophage differentiation	-0.034	0.22	-10000	0	-0.74	21	21
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.063	0.17	-10000	0	-0.45	55	55
JUNB	-0.023	0.2	-10000	0	-0.79	13	13
FOS	-0.026	0.14	-10000	0	-0.53	41	41
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.039	0.16	-10000	0	-0.46	46	46
STAT1/PIAS1	-0.028	0.16	-10000	0	-0.48	33	33
GRB2/SOS1/GAB family/SHP2/PI3K	0.028	0.075	-10000	0	-0.78	4	4
STAT3 (dimer)	-0.037	0.23	-10000	0	-0.78	21	21
PRKCD	-0.02	0.19	-10000	0	-0.6	26	26
IL6R	-0.005	0.1	-10000	0	-0.56	19	19
SOCS3	-0.034	0.18	-10000	0	-0.63	31	31
gp130 (dimer)/JAK1/JAK1/LMO4	0.013	0.082	-10000	0	-0.36	24	24
Rac1/GTP	-0.039	0.18	-10000	0	-0.52	44	44
HCK	-0.018	0.12	-10000	0	-0.55	31	31
MAPKKK cascade	0.013	0.094	-10000	0	-0.8	5	5
bone resorption	-0.066	0.31	-10000	0	-0.93	54	54
IRF1	-0.02	0.2	-10000	0	-0.74	11	11
mol:GDP	-0.048	0.18	-10000	0	-0.51	49	49
SOS1	0.011	0.024	-10000	0	-0.58	1	1
VAV1	-0.049	0.18	-10000	0	-0.52	49	49
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.04	0.17	-10000	0	-0.59	32	32
PTPN11	-0.011	0.086	-10000	0	-0.91	5	5
IL6/IL6RA	-0.081	0.18	-10000	0	-0.38	152	152
gp130 (dimer)/TYK2/TYK2/LMO4	0.011	0.075	-10000	0	-0.34	23	23
gp130 (dimer)/JAK2/JAK2/LMO4	-0.001	0.1	-10000	0	-0.36	42	42
IL6	-0.11	0.22	-10000	0	-0.51	138	138
PIAS3	0.01	0.031	-10000	0	-0.52	2	2
PTPRE	0.006	0.026	-10000	0	-0.57	1	1
PIAS1	0.011	0	-10000	0	-10000	0	0
RAC1	0.012	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.043	0.14	-10000	0	-0.38	54	54
LMO4	0.006	0.062	-10000	0	-0.49	9	9
STAT3 (dimer)/PIAS3	-0.033	0.22	-10000	0	-0.72	24	24
MCL1	0.042	0.063	-10000	0	-0.7	3	3

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.011	0.1	-10000	0	-0.32	47	47
ER alpha/Gai/GDP/Gbeta gamma	-0.021	0.14	-10000	0	-0.44	35	35
AKT1	-0.018	0.17	-10000	0	-0.72	31	31
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.02	0.17	-10000	0	-0.78	28	28
mol:Ca2+	-0.023	0.13	-10000	0	-0.43	31	31
IGF1R	0.01	0.024	-10000	0	-0.58	1	1
E2/ER alpha (dimer)/Striatin	-0.016	0.098	-10000	0	-0.32	55	55
SHC1	0.011	0	-10000	0	-10000	0	0
apoptosis	0.016	0.16	0.68	32	-10000	0	32
RhoA/GTP	-0.028	0.086	-10000	0	-0.57	5	5
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.046	0.12	-10000	0	-0.46	32	32
regulation of stress fiber formation	-0.009	0.094	0.48	10	-10000	0	10
E2/ERA-ERB (dimer)	-0.024	0.11	-10000	0	-0.33	66	66
KRAS	0.006	0.057	-10000	0	-0.56	6	6
G13/GTP	-0.012	0.086	-10000	0	-0.29	51	51
pseudopodium formation	0.009	0.094	-10000	0	-0.48	10	10
E2/ER alpha (dimer)/PELP1	-0.013	0.093	-10000	0	-0.32	50	50
GRB2	0.011	0	-10000	0	-10000	0	0
GNG2	0.004	0.063	-10000	0	-0.53	8	8
GNAO1	-0.046	0.16	-10000	0	-0.49	68	68
HRAS	0.008	0.041	-10000	0	-0.49	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.018	0.14	-10000	0	-0.49	34	34
E2/ER beta (dimer)	-0.005	0.074	-10000	0	-0.4	20	20
mol:GDP	-0.038	0.11	-10000	0	-0.38	44	44
mol:NADP	-0.018	0.14	-10000	0	-0.49	34	34
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
mol:IP3	-0.025	0.13	-10000	0	-0.45	31	31
IGF-1R heterotetramer	0.01	0.024	-10000	0	-0.58	1	1
PLCB1	-0.028	0.13	-10000	0	-0.48	29	29
PLCB2	-0.01	0.11	-10000	0	-0.44	28	28
IGF1	-0.073	0.2	-10000	0	-0.52	94	94
mol:L-citrulline	-0.018	0.14	-10000	0	-0.49	34	34
RHOA	0.01	0.024	-10000	0	-0.58	1	1
Gai/GDP	-0.022	0.15	-10000	0	-0.75	19	19
JNK cascade	-0.005	0.073	-10000	0	-0.4	20	20
BCAR1	0.008	0.044	-10000	0	-0.52	4	4
ESR2	-0.007	0.1	-10000	0	-0.54	20	20
GNAQ	0.005	0.059	-10000	0	-0.58	6	6
ESR1	-0.033	0.15	-10000	0	-0.52	49	49
Gq family/GDP/Gbeta gamma	0.003	0.11	-10000	0	-0.52	20	20
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.009	0.068	-10000	0	-0.31	1	1
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.045	0.11	-10000	0	-0.46	31	31
GNAZ	-0.012	0.11	-10000	0	-0.55	25	25
E2/ER alpha (dimer)	-0.024	0.11	-10000	0	-0.38	49	49
STRN	0.005	0.059	-10000	0	-0.58	6	6
GNAL	-0.02	0.12	-10000	0	-0.5	36	36
PELP1	0.01	0.024	-10000	0	-0.58	1	1
MAPK11	-0.005	0.082	-10000	0	-0.33	35	35
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	-0.003	0.089	-10000	0	-0.56	15	15
HBEGF	-0.036	0.15	-10000	0	-0.51	33	33
cAMP biosynthetic process	-0.044	0.1	-10000	0	-0.32	55	55
SRC	-0.015	0.13	-10000	0	-0.44	30	30
PI3K	0.013	0.04	-10000	0	-0.42	5	5
GNB1	0.011	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.037	0.099	-10000	0	-0.37	34	34
SOS1	0.01	0.024	-10000	0	-0.58	1	1
IGF-1R heterotetramer/IGF1	-0.065	0.13	-10000	0	-0.42	50	50
Gs family/GTP	-0.044	0.11	-10000	0	-0.32	55	55
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.011	0.069	-10000	0	-0.41	13	13
vasodilation	-0.017	0.13	-10000	0	-0.46	34	34
mol:DAG	-0.025	0.13	-10000	0	-0.45	31	31
Gs family/GDP/Gbeta gamma	-0.045	0.1	-10000	0	-0.38	35	35
MSN	0.008	0.1	-10000	0	-0.52	10	10
Gq family/GTP	-0.013	0.11	-10000	0	-0.49	24	24
mol:PI-3-4-5-P3	-0.019	0.17	-10000	0	-0.74	28	28
NRAS	0.001	0.076	-10000	0	-0.58	10	10
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.017	0.13	0.46	34	-10000	0	34
GRB2/SOS1	0.016	0.018	-10000	0	-0.42	1	1
RhoA/GDP	-0.036	0.1	-10000	0	-0.37	43	43
NOS3	-0.02	0.14	-10000	0	-0.52	33	33
GNA11	0.007	0.05	-10000	0	-0.53	5	5
MAPKKK cascade	-0.005	0.14	-10000	0	-0.56	32	32
E2/ER alpha (dimer)/PELP1/Src	-0.048	0.12	-10000	0	-0.47	34	34
ruffle organization	0.009	0.094	-10000	0	-0.48	10	10
ROCK2	0.003	0.11	-10000	0	-0.62	9	9
GNA14	-0.007	0.1	-10000	0	-0.56	19	19
GNA15	-0.008	0.1	-10000	0	-0.54	21	21
GNA13	0.009	0.034	-10000	0	-0.58	2	2
MMP9	-0.041	0.16	-10000	0	-0.54	31	31
MMP2	-0.029	0.15	-10000	0	-0.56	25	25

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.008	0.018	-10000	0	-0.43	1	1
GNB1/GNG2	-0.017	0.1	-10000	0	-0.27	76	76
regulation of S phase of mitotic cell cycle	-0.001	0.073	-10000	0	-0.27	27	27
GNAO1	-0.046	0.16	-10000	0	-0.49	68	68
HRAS	0.008	0.041	-10000	0	-0.49	4	4
SHBG/T-DHT	-0.008	0.061	-10000	0	-0.27	30	30
PELP1	0.01	0.024	-10000	0	-0.58	1	1
AKT1	0.008	0.018	-10000	0	-0.43	1	1
MAP2K1	0	0.089	-10000	0	-0.42	5	5
T-DHT/AR	-0.036	0.12	-10000	0	-0.36	71	71
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-0.006	40	40
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	-0.003	0.089	-10000	0	-0.56	15	15
mol:GDP	-0.033	0.097	-10000	0	-0.44	23	23
cell proliferation	0	0.12	-10000	0	-0.39	28	28
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
FOS	-0.015	0.18	-10000	0	-0.76	29	29
mol:Ca2+	-0.011	0.021	-10000	0	-0.079	18	18
MAPK3	0.001	0.1	-10000	0	-0.47	5	5
MAPK1	0.004	0.062	-10000	0	-0.2	28	28
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
mol:IP3	0	0.001	-10000	0	-0.004	41	41
cAMP biosynthetic process	-0.003	0.061	-10000	0	-0.25	30	30
GNG2	0.004	0.063	-10000	0	-0.53	8	8
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	41	41
HRAS/GTP	-0.031	0.083	-10000	0	-0.3	24	24
actin cytoskeleton reorganization	-0.005	0.046	-10000	0	-0.4	7	7
SRC	0.01	0.024	-10000	0	-0.58	1	1
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	41	41
PI3K	0.012	0.034	-10000	0	-0.36	5	5
apoptosis	0	0.11	0.39	31	-10000	0	31
T-DHT/AR/PELP1	-0.024	0.1	-10000	0	-0.3	72	72
HRAS/GDP	-0.032	0.094	-10000	0	-0.42	24	24
CREB1	-0.001	0.12	-10000	0	-0.42	31	31
RAC1-CDC42/GTP	-0.004	0.047	-10000	0	-0.41	7	7
AR	-0.051	0.16	-10000	0	-0.49	71	71
GNB1	0.011	0	-10000	0	-10000	0	0
RAF1	-0.004	0.089	-10000	0	-0.42	4	4
RAC1-CDC42/GDP	-0.03	0.093	-10000	0	-0.41	24	24
T-DHT/AR/PELP1/Src	-0.014	0.096	-10000	0	-0.27	72	72
MAP2K2	0.001	0.091	-10000	0	-0.47	4	4
T-DHT/AR/PELP1/Src/PI3K	-0.001	0.073	-10000	0	-0.27	27	27
GNAZ	-0.012	0.11	-10000	0	-0.55	25	25
SHBG	-0.014	0.1	-10000	0	-0.46	30	30
Gi family/GNB1/GNG2/GDP	-0.008	0.099	-10000	0	-0.37	20	20
mol:T-DHT	0	0.001	-10000	0	-0.003	23	23
RAC1	0.011	0	-10000	0	-10000	0	0
GNRH1	0.001	0.058	-10000	0	-0.4	12	12
Gi family/GTP	-0.023	0.089	-10000	0	-0.3	16	16
CDC42	0.006	0.054	-10000	0	-0.58	5	5

×

IGF1 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
NCK2	0.01	0.024	-10000	0	-0.58	1	1
PTK2	0.01	0.024	-10000	0	-0.58	1	1
CRKL	-0.022	0.1	-10000	0	-0.3	52	52
GRB2/SOS1/SHC	0.023	0.015	-10000	0	-0.35	1	1
HRAS	0.008	0.041	-10000	0	-0.49	4	4
IRS1/Crk	-0.022	0.1	-10000	0	-0.3	52	52
IGF-1R heterotetramer/IGF1/PTP1B	-0.029	0.12	-10000	0	-0.34	53	53
AKT1	-0.005	0.094	-10000	0	-0.48	4	4
BAD	0	0.093	-10000	0	-0.46	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.023	0.1	-10000	0	-0.3	52	52
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.025	0.11	-10000	0	-0.3	57	57
RAF1	0.005	0.087	-10000	0	-0.41	5	5
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.014	0.1	-10000	0	-0.29	52	52
YWHAZ	0.008	0.042	-10000	0	-0.58	3	3
IGF-1R heterotetramer/IGF1/IRS1	-0.031	0.11	-10000	0	-0.32	59	59
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
RPS6KB1	-0.008	0.1	-10000	0	-0.5	7	7
GNB2L1	0.011	0.019	-10000	0	-0.46	1	1
positive regulation of MAPKKK cascade	0.003	0.077	-10000	0	-0.36	5	5
PXN	0.011	0	-10000	0	-10000	0	0
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.016	0.018	-10000	0	-0.42	1	1
HRAS/GTP	-0.034	0.081	-10000	0	-0.49	4	4
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.007	0.097	-10000	0	-0.44	4	4
IGF-1R heterotetramer	0	0.037	-10000	0	-0.66	1	1
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.022	0.1	-10000	0	-0.3	53	53
Crk/p130 Cas/Paxillin	-0.01	0.097	-10000	0	-0.51	3	3
IGF1R	0	0.038	-10000	0	-0.67	1	1
IGF1	-0.074	0.2	-10000	0	-0.53	94	94
IRS2/Crk	-0.019	0.1	-10000	0	-0.29	57	57
PI3K	-0.016	0.1	-10000	0	-0.29	56	56
apoptosis	-0.005	0.089	0.44	8	-10000	0	8
HRAS/GDP	0.006	0.03	-10000	0	-0.35	4	4
PRKCD	-0.015	0.12	-10000	0	-0.39	52	52
RAF1/14-3-3 E	0.012	0.079	-10000	0	-0.37	4	4
BAD/14-3-3	0.005	0.094	-10000	0	-0.47	8	8
PRKCZ	-0.006	0.096	-10000	0	-0.48	5	5
Crk/p130 Cas/Paxillin/FAK1	-0.032	0.078	-10000	0	-0.44	9	9
PTPN1	0.01	0.024	-10000	0	-0.58	1	1
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.022	0.13	-10000	0	-0.42	52	52
BCAR1	0.008	0.044	-10000	0	-0.52	4	4
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.018	0.11	-10000	0	-0.3	55	55
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.01	0.024	-10000	0	-0.58	1	1
IRS1/NCK2	-0.022	0.1	-10000	0	-0.3	53	53
GRB10	0.007	0.048	-10000	0	-0.58	4	4
PTPN11	-0.025	0.11	-10000	0	-0.3	57	57
IRS1	-0.031	0.11	-10000	0	-0.32	59	59
IRS2	-0.027	0.11	-10000	0	-0.31	57	57
IGF-1R heterotetramer/IGF1	-0.049	0.15	-10000	0	-0.39	94	94
GRB2	0.011	0	-10000	0	-10000	0	0
PDPK1	-0.011	0.098	-10000	0	-0.51	4	4
YWHAE	0.011	0	-10000	0	-10000	0	0
PRKD1	-0.037	0.16	-10000	0	-0.45	66	66
SHC1	0.011	0	-10000	0	-10000	0	0

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.006	0.072	-10000	0	-0.59	8	8
SVIL	0	0.045	-10000	0	-0.49	4	4
ZNF318	0.032	0.049	-10000	0	-10000	0	0
JMJD2C	0.003	0.02	-10000	0	-0.078	25	25
T-DHT/AR/Ubc9	-0.023	0.11	-10000	0	-0.3	71	71
CARM1	0.009	0.024	-10000	0	-0.58	1	1
PRDX1	0.012	0.025	-10000	0	-0.58	1	1
PELP1	0.014	0.026	-10000	0	-0.58	1	1
CTNNB1	0.005	0.016	-10000	0	-10000	0	0
AKT1	0.016	0.028	-10000	0	-0.58	1	1
PTK2B	0.004	0.037	-10000	0	-0.58	2	2
MED1	0.014	0.046	-10000	0	-0.5	4	4
MAK	0.006	0.12	-10000	0	-0.46	30	30
response to oxidative stress	0.001	0.004	-10000	0	-10000	0	0
HIP1	-0.002	0.063	-10000	0	-0.6	6	6
GSN	-0.008	0.076	-10000	0	-0.51	12	12
NCOA2	0.002	0.067	-10000	0	-0.57	8	8
NCOA6	0.004	0.03	-10000	0	-0.58	1	1
DNA-PK	0.04	0.056	0.21	1	-0.38	3	4
NCOA4	0.008	0.034	-10000	0	-0.58	2	2
PIAS3	0.004	0.034	-10000	0	-0.52	2	2
cell proliferation	-0.005	0.1	-10000	0	-0.49	15	15
XRCC5	0.015	0.026	-10000	0	-0.57	1	1
UBE3A	-0.005	0.057	-10000	0	-0.59	4	4
T-DHT/AR/SNURF	-0.077	0.16	-10000	0	-0.33	153	153
FHL2	0.022	0.089	-10000	0	-1.1	2	2
RANBP9	0.004	0.03	-10000	0	-0.58	1	1
JMJD1A	-0.006	0.044	-10000	0	-0.11	75	75
CDK6	0.012	0.019	-10000	0	-0.46	1	1
TGFB1I1	-0.002	0.056	-10000	0	-0.52	6	6
T-DHT/AR/CyclinD1	-0.03	0.11	-10000	0	-0.3	72	72
XRCC6	0.016	0.011	-10000	0	-10000	0	0
T-DHT/AR	-0.02	0.12	-10000	0	-0.37	36	36
CTDSP1	0.007	0.025	-10000	0	-0.58	1	1
CTDSP2	0.025	0.033	-10000	0	-10000	0	0
BRCA1	0.003	0.031	-10000	0	-0.59	1	1
TCF4	0.009	0.086	-10000	0	-0.52	14	14
CDKN2A	-0.064	0.19	-10000	0	-0.5	94	94
SRF	0.022	0.032	-10000	0	-0.45	2	2
NKX3-1	-0.076	0.25	-10000	0	-0.63	80	80
KLK3	-0.16	0.42	-10000	0	-1.4	55	55
TMF1	0.003	0.059	-10000	0	-0.58	6	6
HNRNPA1	0.019	0.018	-10000	0	-10000	0	0
AOF2	-0.009	0.021	-10000	0	-0.069	54	54
APPL1	0.022	0.07	-10000	0	-0.42	12	12
T-DHT/AR/Caspase 8	-0.016	0.11	-10000	0	-0.3	69	69
AR	-0.053	0.17	-10000	0	-0.5	71	71
UBA3	0.007	0.025	-10000	0	-0.59	1	1
PATZ1	0.019	0.018	-10000	0	-10000	0	0
PAWR	0.008	0.025	-10000	0	-0.58	1	1
PRKDC	0.013	0.039	-10000	0	-0.52	3	3
PA2G4	0.02	0.021	-10000	0	-10000	0	0
UBE2I	0.011	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.017	0.1	-10000	0	-0.27	72	72
RPS6KA3	-0.002	0.054	-10000	0	-0.59	4	4
T-DHT/AR/ARA70	-0.029	0.11	-10000	0	-0.31	72	72
LATS2	0.017	0.034	-10000	0	-0.49	2	2
T-DHT/AR/PRX1	-0.01	0.11	-10000	0	-0.28	67	67
Cyclin D3/CDK11 p58	0.007	0.031	-10000	0	-0.32	5	5
VAV3	-0.072	0.2	-10000	0	-0.58	78	78
KLK2	-0.027	0.093	-10000	0	-0.47	10	10
CASP8	0.013	0.025	-10000	0	-0.58	1	1
T-DHT/AR/TIF2/CARM1	-0.025	0.11	-10000	0	-0.33	43	43
TMPRSS2	-0.019	0.11	-10000	0	-1.1	3	3
CCND1	0.007	0.026	-10000	0	-0.59	1	1
PIAS1	-0.001	0.031	-10000	0	-10000	0	0
mol:T-DHT	-0.003	0.023	-10000	0	-0.072	35	35
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.009	0.053	-10000	0	-0.58	1	1
T-DHT/AR/CDK6	-0.021	0.11	-10000	0	-0.3	72	72
CMTM2	-0.029	0.14	-10000	0	-0.52	47	47
SNURF	-0.075	0.2	-10000	0	-0.54	90	90
ZMIZ1	0.008	0.028	-10000	0	-0.44	1	1
CCND3	0.008	0.043	-10000	0	-0.46	5	5
TGIF1	0.019	0.018	-10000	0	-10000	0	0
FKBP4	0.003	0.038	-10000	0	-0.46	3	3

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.009	0.045	-9999	-0.37	8	8
PDGFRB	-0.005	0.092	-9999	-0.54	17	17
SPHK1	-0.045	0.15	-9999	-0.8	21	21
mol:S1P	-0.044	0.14	-9999	-0.69	22	22
S1P1/S1P/Gi	-0.047	0.15	-9999	-0.39	62	62
GNAO1	-0.047	0.16	-9999	-0.49	68	68
PDGFB-D/PDGFRB/PLCgamma1	-0.042	0.15	-9999	-0.49	24	24
PLCG1	-0.042	0.15	-9999	-0.5	22	22
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.005	0.092	-9999	-0.54	17	17
GNAI2	0.01	0.005	-9999	-10000	0	0
GNAI3	0.01	0.005	-9999	-10000	0	0
GNAI1	-0.005	0.09	-9999	-0.56	15	15
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.008	0.039	-9999	-0.31	8	8
S1P1/S1P	-0.02	0.12	-9999	-0.49	26	26
negative regulation of cAMP metabolic process	-0.046	0.15	-9999	-0.38	62	62
MAPK3	-0.061	0.2	-9999	-0.56	57	57
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
RhoA/GDP	0.008	0.018	-9999	-0.43	1	1
KDR	0.004	0.059	-9999	-0.53	7	7
PLCB2	-0.015	0.11	-9999	-0.42	29	29
RAC1	0.011	0	-9999	-10000	0	0
RhoA/GTP	-0.037	0.092	-9999	-0.4	26	26
receptor internalization	-0.04	0.1	-9999	-0.45	26	26
PTGS2	-0.1	0.31	-9999	-0.98	56	56
Rac1/GTP	-0.037	0.091	-9999	-0.4	26	26
RHOA	0.01	0.024	-9999	-0.58	1	1
VEGFA	0.01	0.019	-9999	-0.46	1	1
negative regulation of T cell proliferation	-0.046	0.15	-9999	-0.38	62	62
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.014	0.11	-9999	-0.55	25	25
MAPK1	-0.061	0.2	-9999	-0.56	57	57
S1P1/S1P/PDGFB-D/PDGFRB	-0.021	0.13	-9999	-0.46	29	29
ABCC1	0.01	0.025	-9999	-0.59	1	1

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.011	0.11	-9999	-0.57	22	22
PDGF/PDGFRA/CRKL	0.001	0.08	-9999	-0.4	22	22
positive regulation of JUN kinase activity	0.016	0.063	-9999	-0.3	21	21
CRKL	0.011	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.009	0.086	-9999	-0.41	26	26
AP1	-0.063	0.21	-9999	-0.9	30	30
mol:IP3	0.001	0.086	-9999	-0.42	23	23
PLCG1	0.001	0.086	-9999	-0.42	23	23
PDGF/PDGFRA/alphaV Integrin	-0.007	0.1	-9999	-0.42	32	32
RAPGEF1	0.01	0.024	-9999	-0.58	1	1
CRK	0.011	0.019	-9999	-0.46	1	1
mol:Ca2+	0.001	0.086	-9999	-0.42	23	23
CAV3	-0.002	0.042	-9999	-0.46	5	5
CAV1	-0.002	0.082	-9999	-0.5	16	16
SHC/Grb2/SOS1	0.017	0.063	-9999	-0.3	21	21
PDGF/PDGFRA/Shf	-0.032	0.13	-9999	-0.38	73	73
FOS	-0.03	0.22	-9999	-0.89	30	30
JUN	-0.008	0.042	-9999	-0.44	5	5
oligodendrocyte development	-0.007	0.1	-9999	-0.42	32	32
GRB2	0.011	0	-9999	-10000	0	0
PIK3R1	0.008	0.042	-9999	-0.58	3	3
mol:DAG	0.001	0.086	-9999	-0.42	23	23
PDGF/PDGFRA	-0.011	0.11	-9999	-0.57	22	22
actin cytoskeleton reorganization	0	0.081	-9999	-0.4	23	23
SRF	0.017	0.02	-9999	-0.31	2	2
SHC1	0.011	0	-9999	-10000	0	0
PI3K	0.007	0.076	-9999	-0.35	25	25
PDGF/PDGFRA/Crk/C3G	0.009	0.07	-9999	-0.33	24	24
JAK1	0	0.086	-9999	-0.41	25	25
ELK1/SRF	0.015	0.069	-9999	-0.32	22	22
SHB	0.011	0.019	-9999	-0.46	1	1
SHF	-0.034	0.14	-9999	-0.48	55	55
CSNK2A1	0.005	0.014	-9999	-10000	0	0
GO:0007205	0	0.09	-9999	-0.44	23	23
SOS1	0.01	0.024	-9999	-0.58	1	1
Ras protein signal transduction	0.016	0.063	-9999	-0.3	21	21
PDGF/PDGFRA/SHB	0	0.081	-9999	-0.4	23	23
PDGF/PDGFRA/Caveolin-1	-0.009	0.1	-9999	-0.41	35	35
ITGAV	0	0.08	-9999	-0.58	11	11
ELK1	0.005	0.082	-9999	-0.39	22	22
PIK3CA	0.009	0.034	-9999	-0.58	2	2
PDGF/PDGFRA/Crk	0	0.081	-9999	-0.4	23	23
JAK-STAT cascade	0	0.085	-9999	-0.4	25	25
cell proliferation	-0.032	0.13	-9999	-0.38	73	73

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.01	0.07	0.25	6	-0.56	4	10
DAPP1	-0.066	0.2	-10000	0	-0.52	67	67
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.07	0.23	-10000	0	-0.61	66	66
mol:DAG	-0.015	0.11	0.18	2	-0.28	51	53
HRAS	0.008	0.042	-10000	0	-0.49	4	4
RAP1A	0.01	0.026	-10000	0	-0.62	1	1
ARF5/GDP	0.001	0.1	-10000	0	-0.43	24	24
PLCG2	-0.011	0.11	-10000	0	-0.54	24	24
PLCG1	0.01	0.024	-10000	0	-0.58	1	1
ARF5	0.011	0	-10000	0	-10000	0	0
mol:GTP	-0.011	0.072	0.23	6	-0.6	4	10
ARF1/GTP	-0.01	0.069	0.24	6	-0.56	4	10
RHOA	0.01	0.024	-10000	0	-0.58	1	1
YES1	0.004	0.064	-10000	0	-0.58	7	7
RAP1A/GTP	0.011	0.074	0.22	6	-0.37	13	19
ADAP1	-0.011	0.07	0.22	6	-0.55	5	11
ARAP3	-0.01	0.071	0.23	6	-0.58	4	10
INPPL1	0.01	0.024	-10000	0	-0.58	1	1
PREX1	0.006	0.055	-10000	0	-0.54	6	6
ARHGEF6	-0.005	0.095	-10000	0	-0.54	18	18
ARHGEF7	0.011	0	-10000	0	-10000	0	0
ARF1	0.011	0.019	-10000	0	-0.46	1	1
NRAS	0.002	0.078	-10000	0	-0.59	10	10
FYN	0.005	0.06	-10000	0	-0.55	7	7
ARF6	0.01	0.024	-10000	0	-0.58	1	1
FGR	-0.026	0.14	-10000	0	-0.54	40	40
mol:Ca2+	-0.001	0.055	-10000	0	-0.21	1	1
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.044	0.16	-10000	0	-0.52	62	62
ZAP70	-0.036	0.15	-10000	0	-0.53	52	52
mol:IP3	-0.005	0.076	-10000	0	-0.23	19	19
LYN	0.011	0	-10000	0	-10000	0	0
ARF1/GDP	0	0.11	-10000	0	-0.44	24	24
RhoA/GDP	-0.021	0.081	0.24	3	-0.47	10	13
PDK1/Src/Hsp90	0.022	0.022	-10000	0	-0.35	2	2
BLNK	-0.01	0.11	-10000	0	-0.58	21	21
actin cytoskeleton reorganization	0.014	0.11	0.23	3	-0.48	15	18
SRC	0.01	0.024	-10000	0	-0.58	1	1
PLEKHA2	0.002	0.088	-10000	0	-0.36	32	32
RAC1	0.011	0	-10000	0	-10000	0	0
PTEN	0.004	0.057	-10000	0	-0.56	6	6
HSP90AA1	0.01	0.024	-10000	0	-0.58	1	1
ARF6/GTP	-0.01	0.072	0.25	6	-0.62	4	10
RhoA/GTP	0.016	0.076	0.22	6	-0.63	4	10
Src family/SYK family/BLNK-LAT	-0.066	0.2	-10000	0	-0.57	62	62
BLK	-0.12	0.23	-10000	0	-0.52	139	139
PDPK1	0.011	0	-10000	0	-10000	0	0
CYTH1	-0.01	0.067	0.22	6	-0.56	4	10
HCK	-0.018	0.12	-10000	0	-0.55	31	31
CYTH3	-0.011	0.069	0.22	6	-0.56	4	10
CYTH2	-0.01	0.067	0.22	6	-0.56	4	10
KRAS	0.006	0.059	-10000	0	-0.57	6	6
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.024	0.069	-10000	0	-0.53	5	5
SGK1	-0.01	0.071	0.19	6	-0.6	5	11
INPP5D	-0.017	0.12	-10000	0	-0.58	28	28
mol:GDP	-0.006	0.11	-10000	0	-0.44	25	25
SOS1	0.01	0.024	-10000	0	-0.58	1	1
SYK	0.011	0.019	-10000	0	-0.46	1	1
ARF6/GDP	-0.02	0.081	0.24	3	-0.46	10	13
mol:PI-3-4-5-P3	-0.01	0.074	0.29	6	-0.59	4	10
ARAP3/RAP1A/GTP	0.011	0.075	0.22	6	-0.37	13	19
VAV1	-0.026	0.14	-10000	0	-0.57	38	38
mol:PI-3-4-P2	-0.003	0.097	-10000	0	-0.43	28	28
RAS family/GTP/PI3K Class I	0.012	0.073	-10000	0	-0.38	13	13
PLEKHA1	0.003	0.087	-10000	0	-0.36	31	31
Rac1/GDP	0.001	0.1	-10000	0	-0.43	24	24
LAT	-0.01	0.1	-10000	0	-0.51	24	24
Rac1/GTP	-0.014	0.14	-10000	0	-0.46	39	39
ITK	-0.03	0.096	0.22	5	-0.55	6	11
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.029	0.15	0.21	2	-0.4	53	55
LCK	-0.031	0.14	-10000	0	-0.51	48	48
BTK	-0.029	0.093	0.22	3	-0.55	6	9

×

IL2 signaling events mediated by STAT5

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
GAB2	0.01	0.034	-9999	-0.58	2	2
ELF1	-0.018	0.11	-9999	-0.36	47	47
CCNA2	0.01	0.024	-9999	-0.58	1	1
PIK3CA	0.01	0.034	-9999	-0.58	2	2
JAK3	0.001	0.076	-9999	-0.53	12	12
PIK3R1	0.009	0.042	-9999	-0.58	3	3
JAK1	0.009	0.042	-9999	-0.58	3	3
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.008	0.14	-9999	-0.57	17	17
SHC1	0.012	0.001	-9999	-10000	0	0
SP1	-0.009	0.095	-9999	-0.35	41	41
IL2RA	-0.049	0.23	-9999	-0.69	63	63
IL2RB	-0.016	0.12	-9999	-0.55	30	30
SOS1	0.011	0.024	-9999	-0.58	1	1
IL2RG	-0.001	0.084	-9999	-0.56	13	13
G1/S transition of mitotic cell cycle	-0.018	0.19	-9999	-0.68	42	42
PTPN11	0.007	0.054	-9999	-0.58	5	5
CCND2	-0.034	0.21	-9999	-0.78	44	44
LCK	-0.03	0.14	-9999	-0.51	48	48
GRB2	0.012	0.001	-9999	-10000	0	0
IL2	0.002	0.027	-9999	-0.46	2	2
CDK6	0.011	0.019	-9999	-0.46	1	1
CCND3	0.016	0.12	-9999	-0.55	12	12

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.093	0.28	-9999	-1.1	38	38
RAD9A	0.01	0.024	-9999	-0.58	1	1
AP1	-0.014	0.11	-9999	-0.39	45	45
IFNAR2	0.011	0.025	-9999	-0.58	1	1
AKT1	-0.005	0.059	-9999	-0.22	27	27
ER alpha/Oestrogen	-0.024	0.11	-9999	-0.38	49	49
NFX1/SIN3/HDAC complex	0.033	0.027	-9999	-10000	0	0
EGF	-0.18	0.25	-9999	-0.51	216	216
SMG5	0.01	0.024	-9999	-0.58	1	1
SMG6	0.011	0	-9999	-10000	0	0
SP3/HDAC2	0.017	0.02	-9999	-0.42	1	1
TERT/c-Abl	-0.082	0.26	-9999	-0.96	39	39
SAP18	0.01	0.019	-9999	-0.46	1	1
MRN complex	0.008	0.09	-9999	-0.46	19	19
WT1	-0.17	0.26	-9999	-0.52	204	204
WRN	0.005	0.062	-9999	-0.56	7	7
SP1	0.011	0.025	-9999	-0.58	1	1
SP3	0.01	0.025	-9999	-0.58	1	1
TERF2IP	0.01	0.024	-9999	-0.58	1	1
Telomerase/Nucleolin	-0.091	0.22	-9999	-0.85	39	39
Mad/Max	0.015	0.027	-9999	-0.35	3	3
TERT	-0.098	0.29	-9999	-1.1	38	38
CCND1	-0.076	0.24	-9999	-0.97	33	33
MAX	0.011	0.004	-9999	-10000	0	0
RBBP7	0.01	0.024	-9999	-0.58	1	1
RBBP4	0.01	0.024	-9999	-0.58	1	1
TERF2	0.012	0.009	-9999	-10000	0	0
PTGES3	0.009	0.034	-9999	-0.58	2	2
SIN3A	0.01	0.024	-9999	-0.58	1	1
Telomerase/911	0.019	0.046	-9999	-0.7	1	1
CDKN1B	-0.019	0.12	-9999	-0.5	4	4
RAD1	0.011	0.019	-9999	-0.46	1	1
XRCC5	0.01	0.024	-9999	-0.58	1	1
XRCC6	0.011	0	-9999	-10000	0	0
SAP30	0.009	0.034	-9999	-0.58	2	2
TRF2/PARP2	0.017	0.018	-9999	-0.38	1	1
UBE3A	0.007	0.049	-9999	-0.58	4	4
JUN	0.006	0.052	-9999	-0.56	5	5
E6	0	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0.006	0.036	-9999	-0.43	4	4
FOS	-0.026	0.14	-9999	-0.53	41	41
IFN-gamma/IRF1	-0.033	0.14	-9999	-0.36	87	87
PARP2	0.01	0.024	-9999	-0.58	1	1
BLM	0.006	0.057	-9999	-0.56	6	6
Telomerase	0.003	0.063	-9999	-0.45	6	6
IRF1	0.013	0.028	-9999	-0.45	2	2
ESR1	-0.033	0.15	-9999	-0.52	49	49
KU/TER	0.016	0.018	-9999	-0.42	1	1
ATM/TRF2	0.012	0.048	-9999	-0.38	9	9
ubiquitin-dependent protein catabolic process	0.035	0.036	-9999	-0.38	2	2
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.036	0.037	-9999	-0.39	2	2
HDAC1	0.011	0.001	-9999	-10000	0	0
HDAC2	0.011	0.008	-9999	-10000	0	0
ATM	-0.007	0.053	-9999	-0.44	9	9
SMAD3	0.003	0.079	-9999	-0.4	22	22
ABL1	0.01	0.024	-9999	-0.58	1	1
MXD1	0.008	0.036	-9999	-0.5	3	3
MRE11A	0.003	0.068	-9999	-0.58	8	8
HUS1	0.011	0	-9999	-10000	0	0
RPS6KB1	0.006	0.057	-9999	-0.56	6	6
TERT/NF kappa B1/14-3-3	-0.086	0.24	-9999	-0.98	34	34
NR2F2	0.012	0.007	-9999	-10000	0	0
MAPK3	0.01	0.027	-9999	-0.35	3	3
MAPK1	0.01	0.027	-9999	-0.35	3	3
TGFB1/TGF beta receptor Type II	-0.003	0.088	-9999	-0.55	15	15
NFKB1	0.01	0.024	-9999	-0.58	1	1
HNRNPC	0.011	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.007	0.053	-9999	-0.44	9	9
NBN	-0.005	0.096	-9999	-0.58	16	16
EGFR	0.004	0.063	-9999	-0.54	8	8
mol:Oestrogen	0	0.002	-9999	-10000	0	0
EGF/EGFR	-0.13	0.19	-9999	-0.36	223	223
MYC	0.005	0.058	-9999	-0.56	6	6
IL2	0.001	0.028	-9999	-0.45	2	2
KU	0.016	0.018	-9999	-0.42	1	1
RAD50	0.01	0.024	-9999	-0.58	1	1
HSP90AA1	0.01	0.024	-9999	-0.58	1	1
TGFB1	-0.003	0.088	-9999	-0.55	15	15
TRF2/BLM	0.014	0.04	-9999	-0.37	6	6
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.076	0.26	-9999	-0.98	37	37
SP1/HDAC2	0.017	0.022	-9999	-0.42	1	1
PINX1	0.004	0.064	-9999	-0.58	7	7
Telomerase/EST1A	-0.091	0.22	-9999	-0.85	39	39
Smad3/Myc	0.006	0.076	-9999	-0.33	28	28
911 complex	0.022	0.019	-9999	-0.35	1	1
IFNG	-0.062	0.18	-9999	-0.5	86	86
Telomerase/PinX1	-0.093	0.22	-9999	-0.84	41	41
Telomerase/AKT1/mTOR/p70S6K	0	0.075	-9999	-0.74	2	2
SIN3B	0.01	0.024	-9999	-0.58	1	1
YWHAE	0.011	0	-9999	-10000	0	0
Telomerase/EST1B	-0.091	0.22	-9999	-0.84	40	40
response to DNA damage stimulus	0.001	0.017	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0.02	0.081	-9999	-0.41	16	16
TRF2/WRN	0.013	0.042	-9999	-0.36	7	7
Telomerase/hnRNP C1/C2	-0.091	0.22	-9999	-0.85	39	39
E2F1	0.009	0.037	-9999	-0.5	3	3
ZNFX1	0.011	0.001	-9999	-10000	0	0
PIF1	0.007	0.052	-9999	-0.56	5	5
NCL	0.011	0	-9999	-10000	0	0
DKC1	0.011	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.013	0.1	-10000	0	-0.98	4	4
epithelial cell differentiation	-0.049	0.12	-10000	0	-0.54	16	16
ITCH	0.007	0.056	-10000	0	-0.59	5	5
WWP1	0.017	0.11	-10000	0	-1.5	3	3
FYN	0.005	0.06	-10000	0	-0.55	7	7
EGFR	0.004	0.063	-10000	0	-0.53	8	8
PRL	-0.013	0.089	-10000	0	-0.46	23	23
neuron projection morphogenesis	0.006	0.12	-10000	0	-0.79	4	4
PTPRZ1	-0.08	0.2	-10000	0	-0.5	102	102
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.005	0.13	-10000	0	-1.1	3	3
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.023	0.14	-10000	0	-1.2	3	3
ADAM17	0.011	0.038	-10000	0	-0.63	2	2
ErbB4/ErbB4	0.018	0.1	-10000	0	-1.1	4	4
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0	0.1	-10000	0	-1	4	4
NCOR1	0.01	0.024	-10000	0	-0.58	1	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.019	0.14	-10000	0	-1	4	4
GRIN2B	-0.037	0.16	-10000	0	-0.66	16	16
ErbB4/ErbB2/betacellulin	0.013	0.11	-10000	0	-0.96	4	4
STAT1	0.006	0.051	-10000	0	-0.5	6	6
HBEGF	0.001	0.068	-10000	0	-0.46	13	13
PRLR	-0.042	0.17	-10000	0	-0.58	54	54
E4ICDs/ETO2	-0.036	0.15	-10000	0	-0.39	47	47
axon guidance	0.015	0.13	-10000	0	-1.1	4	4
NEDD4	0.008	0.048	-10000	0	-0.57	4	4
Prolactin receptor/Prolactin receptor/Prolactin	-0.039	0.14	-10000	0	-0.42	71	71
CBFA2T3	-0.082	0.2	-10000	0	-0.5	108	108
ErbB4/ErbB2/HBEGF	0.015	0.1	-10000	0	-1.1	3	3
MAPK3	0.001	0.12	-10000	0	-0.83	4	4
STAT1 (dimer)	0.016	0.11	-10000	0	-1.1	4	4
MAPK1	0.001	0.12	-10000	0	-0.94	3	3
JAK2	-0.008	0.1	-10000	0	-0.55	21	21
ErbB4/ErbB2/neuregulin 1 beta	-0.022	0.14	-10000	0	-0.91	5	5
NRG1	-0.041	0.15	-10000	0	-0.39	88	88
NRG3	-0.003	0.065	-10000	0	-0.46	12	12
NRG2	-0.017	0.1	-10000	0	-0.46	32	32
NRG4	-0.022	0.12	-10000	0	-0.47	38	38
heart development	0.015	0.13	-10000	0	-1.1	4	4
neural crest cell migration	-0.022	0.14	-10000	0	-0.87	5	5
ERBB2	0.01	0.06	-10000	0	-0.34	16	16
WWOX/E4ICDs	0.018	0.095	-10000	0	-0.76	6	6
SHC1	0.011	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.003	0.12	-10000	0	-0.87	6	6
apoptosis	0.036	0.096	0.99	4	-10000	0	4
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.002	0.12	-10000	0	-1.1	4	4
ErbB4/ErbB2/epiregulin	-0.074	0.17	-10000	0	-0.53	16	16
ErbB4/ErbB4/betacellulin/betacellulin	0.011	0.11	-10000	0	-0.48	17	17
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.019	0.16	-10000	0	-0.61	20	20
MDM2	0.019	0.1	-10000	0	-0.9	5	5
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.022	0.14	-10000	0	-0.78	6	6
STAT5A	0.02	0.12	-10000	0	-1.1	4	4
ErbB4/EGFR/neuregulin 1 beta	-0.02	0.14	-10000	0	-1.1	4	4
DLG4	0.007	0.048	-10000	0	-0.51	5	5
GRB2/SHC	0.017	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.016	0.09	-10000	0	-0.81	5	5
STAT5A (dimer)	-0.052	0.13	-10000	0	-0.61	16	16
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.019	0.12	-10000	0	-1.1	4	4
LRIG1	-0.002	0.087	-10000	0	-0.58	13	13
EREG	-0.16	0.26	-10000	0	-0.55	187	187
BTC	-0.002	0.087	-10000	0	-0.58	13	13
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.015	0.13	-10000	0	-1.2	4	4
ERBB4	0.018	0.1	-10000	0	-1.1	4	4
STAT5B	0.011	0	-10000	0	-10000	0	0
YAP1	0.003	0.086	-10000	0	-1.1	3	3
GRB2	0.011	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.001	0.11	-10000	0	-0.96	4	4
glial cell differentiation	-0.016	0.087	0.79	5	-10000	0	5
WWOX	0.009	0.034	-10000	0	-0.58	2	2
cell proliferation	-0.015	0.15	-10000	0	-0.73	8	8

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.025	0.17	-10000	0	-1.2	11	11
VDR	0.01	0.024	-10000	0	-0.58	1	1
FAM120B	0.01	0.024	-10000	0	-0.58	1	1
RXRs/LXRs/DNA/9cRA	0.025	0.085	-10000	0	-0.58	3	3
RXRs/LXRs/DNA/Oxysterols	0.025	0.12	-10000	0	-0.43	29	29
MED1	0.008	0.044	-10000	0	-0.52	4	4
mol:9cRA	0.002	0.013	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.02	0.12	-10000	0	-0.48	9	9
RXRs/NUR77	0.008	0.091	-10000	0	-0.42	7	7
RXRs/PPAR	0.021	0.058	-10000	0	-0.52	2	2
NCOR2	0.008	0.046	-10000	0	-0.55	4	4
VDR/VDR/Vit D3	0.008	0.018	-10000	0	-0.43	1	1
RARs/VDR/DNA/Vit D3	0.012	0.07	-10000	0	-0.33	18	18
RARA	0.007	0.045	-10000	0	-0.48	5	5
NCOA1	0.01	0.024	-10000	0	-0.58	1	1
VDR/VDR/DNA	0.01	0.024	-10000	0	-0.58	1	1
RARs/RARs/DNA/9cRA	0.008	0.067	-10000	0	-0.28	28	28
RARG	0.005	0.059	-10000	0	-0.58	6	6
RPS6KB1	-0.008	0.081	-10000	0	-0.46	17	17
RARs/THRs/DNA/SMRT	-0.022	0.12	-10000	0	-0.53	8	8
THRA	0.008	0.041	-10000	0	-0.49	4	4
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.008	0.018	-10000	0	-0.43	1	1
RXRs/PPAR/9cRA/PGJ2/DNA	0.021	0.073	0.28	8	-0.32	4	12
NR1H4	-0.12	0.22	-10000	0	-0.5	152	152
RXRs/LXRs/DNA	0.034	0.078	-10000	0	-0.72	1	1
NR1H2	0.013	0.027	-10000	0	-0.6	1	1
NR1H3	0.013	0.024	-10000	0	-0.49	1	1
RXRs/VDR/DNA/Vit D3	0.022	0.058	-10000	0	-0.28	5	5
NR4A1	-0.018	0.11	-10000	0	-0.46	37	37
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.032	0.1	-10000	0	-0.26	66	66
RXRG	-0.009	0.095	-10000	0	-0.46	25	25
RXR alpha/CCPG	0.018	0.027	-10000	0	-0.42	2	2
RXRA	0.013	0.027	-10000	0	-0.59	1	1
RXRB	0.014	0.012	-10000	0	-10000	0	0
THRB	-0.071	0.2	-10000	0	-0.56	86	86
PPARG	0.004	0.064	-10000	0	-0.58	7	7
PPARD	0.01	0.024	-10000	0	-0.58	1	1
TNF	0.003	0.22	-10000	0	-1	23	23
mol:Oxysterols	0.002	0.012	-10000	0	-10000	0	0
cholesterol transport	0.025	0.12	-10000	0	-0.42	29	29
PPARA	0.009	0.034	-10000	0	-0.58	2	2
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	-0.005	0.095	-10000	0	-0.54	18	18
RXRs/NUR77/BCL2	0.001	0.07	-10000	0	-0.28	21	21
SREBF1	0.029	0.12	-10000	0	-0.82	4	4
RXRs/RXRs/DNA/9cRA	0.021	0.073	0.28	8	-0.32	4	12
ABCA1	0.019	0.17	-10000	0	-1.1	10	10
RARs/THRs	-0.027	0.13	-10000	0	-0.32	88	88
RXRs/FXR	-0.052	0.14	-10000	0	-0.33	66	66
BCL2	-0.008	0.1	-10000	0	-0.55	20	20

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.077	0.2	-9999	-0.51	102	102
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.005	0.056	-9999	-0.47	8	8
TCEB1	0.011	0.019	-9999	-0.46	1	1
HIF1A/p53	-0.008	0.095	-9999	-0.28	56	56
HIF1A	0.013	0.036	-9999	-0.31	1	1
COPS5	0.011	0.019	-9999	-0.46	1	1
VHL/Elongin B/Elongin C/RBX1/CUL2	0.029	0.042	-9999	-0.38	4	4
FIH (dimer)	0.011	0	-9999	-10000	0	0
CDKN2A	-0.071	0.19	-9999	-0.51	94	94
ARNT/IPAS	-0.048	0.14	-9999	-0.36	103	103
HIF1AN	0.011	0	-9999	-10000	0	0
GNB2L1	0.011	0.019	-9999	-0.46	1	1
HIF1A/ARNT	0.019	0.04	-9999	-0.4	2	2
CUL2	0.011	0	-9999	-10000	0	0
OS9	0.011	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.018	0.04	-9999	-0.3	9	9
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.019	0.04	-9999	-0.4	2	2
PHD1-3/OS9	0.019	0.055	-9999	-0.32	10	10
HIF1A/RACK1/Elongin B/Elongin C	0.026	0.055	-9999	-0.4	8	8
VHL	0.01	0.024	-9999	-0.58	1	1
HSP90AA1	0.01	0.024	-9999	-0.58	1	1
HIF1A/JAB1	0.02	0.036	-9999	-0.29	1	1
EGLN3	-0.004	0.089	-9999	-0.52	17	17
EGLN2	0.009	0.036	-9999	-0.5	3	3
EGLN1	0.011	0	-9999	-10000	0	0
TP53	-0.044	0.17	-9999	-0.58	56	56
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.027	0.045	-9999	-0.86	1	1
ARNT	0.01	0.024	-9999	-0.58	1	1
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.01	0.031	-9999	-0.52	2	2
HIF1A/p19ARF	-0.02	0.1	-9999	-0.29	45	45

×

Regulation of nuclear SMAD2/3 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.007	0.048	-10000	0	-0.57	4	4
HSPA8	0.01	0.034	-10000	0	-0.58	2	2
SMAD3/SMAD4/ER alpha	-0.034	0.11	0.2	7	-0.34	53	60
AKT1	0.011	0.027	-10000	0	-0.58	1	1
GSC	-0.016	0.14	-10000	0	-0.86	9	9
NKX2-5	-0.014	0.085	-10000	0	-0.46	21	21
muscle cell differentiation	0.038	0.091	0.45	16	-10000	0	16
SMAD2-3/SMAD4/SP1	0.024	0.099	-10000	0	-0.34	14	14
SMAD4	-0.001	0.075	-10000	0	-0.56	7	7
CBFB	0.007	0.048	-10000	0	-0.58	4	4
SAP18	0.011	0.019	-10000	0	-0.46	1	1
Cbp/p300/MSG1	-0.036	0.12	-10000	0	-0.29	112	112
SMAD3/SMAD4/VDR	-0.007	0.058	-10000	0	-0.37	5	5
MYC	0.006	0.058	-10000	0	-0.55	6	6
CDKN2B	-0.011	0.22	-10000	0	-0.95	24	24
AP1	0.01	0.11	-10000	0	-0.45	16	16
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.038	0.055	-10000	0	-0.44	2	2
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.006	0.086	-10000	0	-0.32	19	19
SP3	0.012	0.024	-10000	0	-0.58	1	1
CREB1	0.009	0.034	-10000	0	-0.58	2	2
FOXH1	-0.053	0.17	-10000	0	-0.5	74	74
SMAD3/SMAD4/GR	-0.012	0.1	-10000	0	-0.36	36	36
GATA3	-0.026	0.13	-10000	0	-0.54	31	31
SKI/SIN3/HDAC complex/NCoR1	0.036	0.024	-10000	0	-10000	0	0
MEF2C/TIF2	-0.019	0.13	-10000	0	-0.48	22	22
endothelial cell migration	0.036	0.2	1.3	11	-10000	0	11
MAX	0.013	0.01	-10000	0	-10000	0	0
RBBP7	0.01	0.024	-10000	0	-0.58	1	1
RBBP4	0.01	0.024	-10000	0	-0.58	1	1
RUNX2	-0.006	0.097	-10000	0	-0.54	19	19
RUNX3	-0.02	0.12	-10000	0	-0.51	36	36
RUNX1	0.011	0	-10000	0	-10000	0	0
CTBP1	0.01	0.024	-10000	0	-0.58	1	1
NR3C1	-0.013	0.11	-10000	0	-0.52	28	28
VDR	0.01	0.024	-10000	0	-0.58	1	1
CDKN1A	0.028	0.13	-10000	0	-1.4	3	3
KAT2B	-0.006	0.099	-10000	0	-0.58	17	17
SMAD2/SMAD2/SMAD4/FOXH1	-0.022	0.13	-10000	0	-0.36	44	44
DCP1A	0.011	0	-10000	0	-10000	0	0
SKI	0.011	0.001	-10000	0	-10000	0	0
SERPINE1	-0.036	0.2	-10000	0	-1.3	11	11
SMAD3/SMAD4/ATF2	0.011	0.076	-10000	0	-0.33	15	15
SMAD3/SMAD4/ATF3	0.003	0.092	-10000	0	-0.34	22	22
SAP30	0.009	0.034	-10000	0	-0.58	2	2
Cbp/p300/PIAS3	0.019	0.04	-10000	0	-0.33	6	6
JUN	0.009	0.11	-10000	0	-0.44	16	16
SMAD3/SMAD4/IRF7	0.009	0.085	-10000	0	-0.4	10	10
TFE3	0.014	0.013	-10000	0	-10000	0	0
COL1A2	-0.047	0.21	-10000	0	-0.84	33	33
mesenchymal cell differentiation	-0.001	0.095	0.34	30	-10000	0	30
DLX1	-0.043	0.15	-10000	0	-0.46	65	65
TCF3	0.01	0.024	-10000	0	-0.58	1	1
FOS	-0.024	0.14	-10000	0	-0.53	41	41
SMAD3/SMAD4/Max	0.005	0.07	-10000	0	-0.32	12	12
Cbp/p300/SNIP1	0.02	0.031	-10000	0	-0.35	4	4
ZBTB17	0.01	0.026	-10000	0	-0.58	1	1
LAMC1	0.023	0.066	-10000	0	-0.43	1	1
TGIF2/HDAC complex/SMAD3/SMAD4	0.009	0.08	-10000	0	-0.34	18	18
IRF7	0.006	0.057	-10000	0	-0.56	6	6
ESR1	-0.031	0.14	-10000	0	-0.51	49	49
HNF4A	0.004	0.064	-10000	0	-0.58	7	7
MEF2C	-0.022	0.13	-10000	0	-0.5	20	20
SMAD2-3/SMAD4	0.013	0.085	-10000	0	-0.35	16	16
Cbp/p300/Src-1	0.019	0.04	-10000	0	-0.43	4	4
IGHV3OR16-13	-0.009	0.05	-10000	0	-0.8	2	2
TGIF2/HDAC complex	0.006	0.054	-10000	0	-0.58	5	5
CREBBP	0.011	0.006	-10000	0	-10000	0	0
SKIL	0	0.08	-10000	0	-0.58	11	11
HDAC1	0.011	0.001	-10000	0	-10000	0	0
HDAC2	0.011	0.001	-10000	0	-10000	0	0
SNIP1	0.011	0.002	-10000	0	-10000	0	0
GCN5L2	0	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.022	0.076	-10000	0	-0.36	4	4
MSG1/HSC70	-0.051	0.14	-10000	0	-0.34	111	111
SMAD2	0.007	0.052	-10000	0	-0.57	4	4
SMAD3	0.001	0.075	-10000	0	-0.57	7	7
SMAD3/E2F4-5/DP1/p107/SMAD4	0.019	0.069	-10000	0	-0.32	6	6
SMAD2/SMAD2/SMAD4	-0.004	0.076	-10000	0	-0.35	24	24
NCOR1	0.01	0.024	-10000	0	-0.58	1	1
NCOA2	0.004	0.067	-10000	0	-0.56	8	8
NCOA1	0.01	0.024	-10000	0	-0.58	1	1
MYOD/E2A	0.007	0.026	-10000	0	-0.35	3	3
SMAD2-3/SMAD4/SP1/MIZ-1	0.031	0.095	-10000	0	-0.37	7	7
IFNB1	0.009	0.082	-10000	0	-0.48	6	6
SMAD3/SMAD4/MEF2C	-0.018	0.14	-10000	0	-0.49	23	23
CITED1	-0.08	0.19	-10000	0	-0.49	109	109
SMAD2-3/SMAD4/ARC105	0.021	0.078	-10000	0	-0.37	8	8
RBL1	0.009	0.039	-10000	0	-0.54	3	3
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.024	0.1	-10000	0	-0.48	17	17
RUNX1-3/PEBPB2	0.001	0.083	-10000	0	-0.3	40	40
SMAD7	0.027	0.12	-10000	0	-0.69	5	5
MYC/MIZ-1	0.012	0.051	-10000	0	-0.4	7	7
SMAD3/SMAD4	-0.016	0.099	0.31	4	-0.42	16	20
IL10	-0.036	0.2	-10000	0	-0.58	59	59
PIASy/HDAC complex	0.011	0.025	-10000	0	-0.58	1	1
PIAS3	0.009	0.031	-10000	0	-0.52	2	2
CDK2	0.01	0.025	-10000	0	-0.58	1	1
IL5	-0.014	0.13	-10000	0	-0.49	18	18
CDK4	0.011	0.006	-10000	0	-10000	0	0
PIAS4	0.011	0.025	-10000	0	-0.58	1	1
ATF3	-0.004	0.083	-10000	0	-0.46	19	19
SMAD3/SMAD4/SP1	0.014	0.095	-10000	0	-0.34	15	15
FOXG1	-0.063	0.16	-10000	0	-0.48	79	79
FOXO3	0.018	0.025	-10000	0	-0.42	1	1
FOXO1	0.017	0.035	-10000	0	-0.42	3	3
FOXO4	0.017	0.03	-10000	0	-0.42	2	2
heart looping	-0.022	0.13	-10000	0	-0.5	20	20
CEBPB	0.008	0.041	-10000	0	-0.49	4	4
SMAD3/SMAD4/DLX1	-0.022	0.12	-10000	0	-0.35	24	24
MYOD1	-0.001	0.026	-10000	0	-0.46	2	2
SMAD3/SMAD4/HNF4	0.008	0.087	-10000	0	-0.37	19	19
SMAD3/SMAD4/GATA3	-0.026	0.14	-10000	0	-0.45	27	27
SnoN/SIN3/HDAC complex/NCoR1	0	0.08	-10000	0	-0.58	11	11
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.008	0.098	-10000	0	-0.38	13	13
SMAD3/SMAD4/SP1-3	0.026	0.087	-10000	0	-0.34	4	4
MED15	0.01	0.024	-10000	0	-0.58	1	1
SP1	0.008	0.044	-10000	0	-0.57	1	1
SIN3B	0.01	0.024	-10000	0	-0.58	1	1
SIN3A	0.01	0.024	-10000	0	-0.58	1	1
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.024	0.13	-10000	0	-0.36	41	41
ITGB5	0.028	0.076	-10000	0	-0.36	1	1
TGIF/SIN3/HDAC complex/CtBP	0.036	0.028	-10000	0	-0.46	1	1
SMAD3/SMAD4/AR	-0.027	0.13	-10000	0	-0.35	56	56
AR	-0.051	0.16	-10000	0	-0.49	71	71
negative regulation of cell growth	0.02	0.08	-10000	0	-0.34	16	16
SMAD3/SMAD4/MYOD	0.005	0.073	-10000	0	-0.32	13	13
E2F5	-0.002	0.087	-10000	0	-0.58	13	13
E2F4	0.011	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.006	0.11	-10000	0	-0.36	20	20
SMAD2-3/SMAD4/FOXO1-3a-4	0.025	0.08	-10000	0	-0.34	18	18
TFDP1	0.011	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.011	0.11	-10000	0	-0.45	16	16
SMAD3/SMAD4/RUNX2	0.001	0.096	-10000	0	-0.35	29	29
TGIF2	0.006	0.054	-10000	0	-0.58	5	5
TGIF1	0.011	0	-10000	0	-10000	0	0
ATF2	0.009	0.034	-10000	0	-0.58	2	2

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.009	0.036	-9999	-0.5	3	3
SPHK1	-0.03	0.14	-9999	-0.51	47	47
GNAI2	0.011	0	-9999	-10000	0	0
mol:S1P	-0.001	0.068	-9999	-0.3	23	23
GNAO1	-0.046	0.16	-9999	-0.49	68	68
mol:Sphinganine-1-P	-0.014	0.11	-9999	-0.36	50	50
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.018	0.054	-9999	-0.29	2	2
GNAI3	0.011	0	-9999	-10000	0	0
G12/G13	0.015	0.025	-9999	-0.42	2	2
S1PR3	0.005	0.058	-9999	-0.53	7	7
S1PR2	0.011	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.004	0.058	-9999	-0.25	23	23
S1PR5	0	0.076	-9999	-0.53	12	12
S1PR4	-0.024	0.14	-9999	-0.53	39	39
GNAI1	-0.003	0.089	-9999	-0.56	15	15
S1P/S1P5/G12	0.006	0.068	-9999	-0.32	9	9
S1P/S1P3/Gq	-0.001	0.11	-9999	-0.35	36	36
S1P/S1P4/Gi	-0.023	0.12	-9999	-0.46	21	21
GNAQ	0.005	0.059	-9999	-0.58	6	6
GNAZ	-0.012	0.11	-9999	-0.55	25	25
GNA14	-0.007	0.1	-9999	-0.56	19	19
GNA15	-0.008	0.1	-9999	-0.54	21	21
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.009	0.034	-9999	-0.58	2	2
GNA11	0.007	0.05	-9999	-0.53	5	5
ABCC1	0.01	0.024	-9999	-0.58	1	1

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.004	0.092	-9999	-0.54	17	17
alphaV beta3 Integrin	-0.004	0.094	-9999	-0.41	29	29
PTK2	-0.027	0.099	-9999	-0.43	28	28
positive regulation of JNK cascade	-0.017	0.068	-9999	-0.31	28	28
CDC42/GDP	0.017	0.11	-9999	-0.42	29	29
Rac1/GDP	0.02	0.1	-9999	-0.42	27	27
RAP1B	0.011	0	-9999	-10000	0	0
RAP1A	0.01	0.024	-9999	-0.58	1	1
CTNNB1	0.011	0	-9999	-10000	0	0
CDC42/GTP	-0.021	0.083	-9999	-0.38	28	28
nectin-3/I-afadin	-0.003	0.09	-9999	-0.42	27	27
RAPGEF1	0.019	0.11	-9999	-0.46	27	27
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0.12	-9999	-0.52	27	27
PDGFB-D/PDGFRB	-0.004	0.092	-9999	-0.54	17	17
TLN1	0.013	0.059	-9999	-0.54	3	3
Rap1/GTP	-0.016	0.069	-9999	-0.32	27	27
IQGAP1	0.009	0.039	-9999	-0.54	3	3
Rap1/GTP/I-afadin	0.02	0.024	-9999	-0.32	3	3
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.003	0.09	-9999	-0.42	27	27
PVR	0.011	0	-9999	-10000	0	0
Necl-5(dimer)	0.011	0	-9999	-10000	0	0
mol:GDP	0.013	0.13	-9999	-0.53	27	27
MLLT4	0.009	0.034	-9999	-0.58	2	2
PIK3CA	0.009	0.034	-9999	-0.58	2	2
PI3K	0.008	0.09	-9999	-0.31	40	40
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.014	0.036	-9999	-0.42	4	4
positive regulation of lamellipodium assembly	-0.026	0.085	-9999	-0.3	49	49
PVRL1	0.009	0.034	-9999	-0.58	2	2
PVRL3	-0.013	0.12	-9999	-0.58	25	25
PVRL2	0.01	0.031	-9999	-0.52	2	2
PIK3R1	0.008	0.042	-9999	-0.58	3	3
CDH1	0.01	0.024	-9999	-0.58	1	1
CLDN1	-0.014	0.12	-9999	-0.56	26	26
JAM-A/CLDN1	-0.001	0.096	-9999	-0.32	48	48
SRC	0.006	0.13	-9999	-0.57	27	27
ITGB3	-0.006	0.098	-9999	-0.54	19	19
nectin-1(dimer)/I-afadin/I-afadin	0.014	0.036	-9999	-0.42	4	4
FARP2	0.016	0.12	-9999	-0.5	27	27
RAC1	0.011	0	-9999	-10000	0	0
CTNNA1	0.009	0.034	-9999	-0.58	2	2
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.006	0.078	-9999	-0.35	27	27
nectin-1/I-afadin	0.014	0.036	-9999	-0.42	4	4
nectin-2/I-afadin	0.014	0.034	-9999	-0.4	4	4
RAC1/GTP/IQGAP1/filamentous actin	0.014	0.025	-9999	-0.33	3	3
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.005	0.081	-9999	-0.35	29	29
CDC42/GTP/IQGAP1/filamentous actin	0.011	0.05	-9999	-0.45	6	6
F11R	0.011	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.017	0.068	-9999	-0.31	28	28
alphaV/beta3 Integrin/Talin	0.011	0.09	-9999	-0.52	7	7
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.014	0.034	-9999	-0.4	4	4
nectin-2(dimer)/I-afadin/I-afadin	0.014	0.034	-9999	-0.4	4	4
PIP5K1C	0.008	0.059	-9999	-0.47	3	3
VAV2	-0.005	0.16	-9999	-0.52	49	49
RAP1/GDP	-0.022	0.084	-9999	-0.39	27	27
ITGAV	0	0.08	-9999	-0.58	11	11
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.005	0.08	-9999	-0.35	29	29
nectin-3(dimer)/I-afadin/I-afadin	-0.003	0.09	-9999	-0.42	27	27
Rac1/GTP	-0.032	0.1	-9999	-0.36	49	49
PTPRM	0.002	0.063	-9999	-0.24	27	27
E-cadherin/beta catenin/alpha catenin	-0.004	0.037	-9999	-0.57	1	1
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.006	0.054	-9999	-0.58	5	5

×

Signaling events mediated by PRL

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
CCNE1	0.009	0.033	-10000	0	-0.46	3	3
mol:Halofuginone	0.004	0.01	-10000	0	-0.23	1	1
ITGA1	0.006	0.054	-10000	0	-0.58	5	5
CDKN1A	0.019	0.048	-10000	0	-0.49	3	3
PRL-3/alpha Tubulin	-0.006	0.093	-10000	0	-0.37	36	36
mol:Ca2+	-0.008	0.12	0.3	34	-0.39	37	71
AGT	-0.024	0.14	-10000	0	-0.53	39	39
CCNA2	0.02	0.067	-10000	0	-0.89	1	1
TUBA1B	0.011	0	-10000	0	-10000	0	0
EGR1	0.004	0.076	-10000	0	-0.35	25	25
CDK2/Cyclin E1	0.027	0.047	-10000	0	-0.43	3	3
MAPK3	-0.006	0.095	-10000	0	-0.37	37	37
PRL-2 /Rab GGTase beta	0.015	0.031	-10000	0	-0.42	3	3
MAPK1	-0.006	0.095	-10000	0	-0.37	37	37
PTP4A1	0.016	0.07	-10000	0	-0.94	1	1
PTP4A3	-0.021	0.13	-10000	0	-0.52	36	36
PTP4A2	0.011	0	-10000	0	-10000	0	0
ITGB1	-0.005	0.093	-10000	0	-0.37	36	36
SRC	0.01	0.024	-10000	0	-0.58	1	1
RAC1	0.005	0.085	-10000	0	-0.42	19	19
Rab GGTase beta/Rab GGTase alpha	0.014	0.036	-10000	0	-0.42	4	4
PRL-1/ATF-5	0.02	0.066	-10000	0	-0.89	1	1
RABGGTA	0.01	0.024	-10000	0	-0.58	1	1
BCAR1	0.015	0.076	0.3	34	-0.33	2	36
RHOC	0.005	0.085	-10000	0	-0.42	19	19
RHOA	0.004	0.087	-10000	0	-0.41	21	21
cell motility	0.004	0.092	-10000	0	-0.42	21	21
PRL-1/alpha Tubulin	0.02	0.066	-10000	0	-0.89	1	1
PRL-3/alpha1 Integrin	-0.01	0.1	-10000	0	-0.38	41	41
ROCK1	0.004	0.093	-10000	0	-0.43	21	21
RABGGTB	0.008	0.042	-10000	0	-0.58	3	3
CDK2	0.01	0.024	-10000	0	-0.58	1	1
mitosis	0.016	0.07	-10000	0	-0.93	1	1
ATF5	0.011	0.019	-10000	0	-0.46	1	1

×

FOXM1 transcription factor network

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
NFATC3	0.074	0.32	-9999	-0.99	16	16
PLK1	0.042	0.073	-9999	-1.4	1	1
BIRC5	0.044	0.047	-9999	-10000	0	0
HSPA1B	0.06	0.34	-9999	-1	19	19
MAP2K1	0.028	0.049	-9999	-0.63	2	2
BRCA2	0.057	0.37	-9999	-1.2	28	28
FOXM1	0.062	0.38	-9999	-1.3	17	17
XRCC1	0.073	0.32	-9999	-1	16	16
FOXM1B/p19	-0.12	0.28	-9999	-1.1	25	25
Cyclin D1/CDK4	0.071	0.3	-9999	-1	7	7
CDC2	0.069	0.33	-9999	-1	16	16
TGFA	0.072	0.31	-9999	-1	9	9
SKP2	0.073	0.32	-9999	-1	15	15
CCNE1	0.013	0.034	-9999	-0.46	3	3
CKS1B	0.073	0.32	-9999	-1.1	7	7
RB1	-0.063	0.18	-9999	-0.96	18	18
FOXM1C/SP1	0.062	0.34	-9999	-1.1	17	17
AURKB	0.045	0.043	-9999	-10000	0	0
CENPF	0.062	0.36	-9999	-1.3	15	15
CDK4	0.019	0.012	-9999	-10000	0	0
MYC	0.075	0.3	-9999	-0.9	19	19
CHEK2	0.029	0.041	-9999	-0.63	1	1
ONECUT1	0.068	0.31	-9999	-0.97	16	16
CDKN2A	-0.074	0.19	-9999	-0.51	94	94
LAMA4	0.072	0.33	-9999	-1.1	15	15
FOXM1B/HNF6	0.063	0.34	-9999	-1.2	16	16
FOS	0.035	0.39	-9999	-1.1	30	30
SP1	0.011	0.024	-9999	-0.58	1	1
CDC25B	0.073	0.32	-9999	-1	15	15
response to radiation	0.016	0.028	-9999	-10000	0	0
CENPB	0.073	0.32	-9999	-1	17	17
CENPA	0.072	0.33	-9999	-1	17	17
NEK2	0.073	0.32	-9999	-1	15	15
HIST1H2BA	0.067	0.32	-9999	-1	11	11
CCNA2	0.014	0.026	-9999	-0.59	1	1
EP300	0.007	0.048	-9999	-0.58	4	4
CCNB1/CDK1	0.064	0.35	-9999	-1.2	16	16
CCNB2	0.071	0.32	-9999	-1.1	8	8
CCNB1	0.071	0.33	-9999	-1.1	15	15
ETV5	0.057	0.36	-9999	-1.1	22	22
ESR1	0.035	0.4	-9999	-1.1	37	37
CCND1	0.074	0.31	-9999	-1	7	7
GSK3A	0.028	0.026	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.038	0.049	-9999	-0.5	2	2
CDK2	0.014	0.026	-9999	-0.59	1	1
G2/M transition of mitotic cell cycle	0.018	0.033	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.089	0.24	-9999	-1.1	17	17
GAS1	-0.049	0.51	-9999	-1.2	83	83
MMP2	0.035	0.41	-9999	-1.2	36	36
RB1/FOXM1C	0.07	0.33	-9999	-1	20	20
CREBBP	0.011	0	-9999	-10000	0	0

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.011	0.038	-10000	0	-0.36	6	6
RAS family/GTP	-0.001	0.096	-10000	0	-0.41	7	7
NFATC4	0.004	0.087	-10000	0	-0.42	4	4
ERBB2IP	-0.008	0.11	-10000	0	-0.58	20	20
HSP90 (dimer)	0.01	0.024	-10000	0	-0.58	1	1
mammary gland morphogenesis	-0.01	0.1	0.22	5	-0.45	3	8
JUN	0.006	0.1	0.16	3	-0.28	48	51
HRAS	0.008	0.041	-10000	0	-0.49	4	4
DOCK7	-0.003	0.099	-10000	0	-0.4	4	4
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.018	0.12	0.23	13	-0.31	51	64
AKT1	0.008	0.018	-10000	0	-0.44	1	1
BAD	0.014	0.031	-10000	0	-0.48	2	2
MAPK10	-0.007	0.082	-10000	0	-0.29	18	18
mol:GTP	0	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.009	0.11	0.24	5	-0.49	3	8
RAF1	0.009	0.098	-10000	0	-0.36	11	11
ErbB2/ErbB3/neuregulin 2	0	0.074	0.23	12	-0.25	39	51
STAT3	0	0.044	-10000	0	-1.1	1	1
cell migration	0.008	0.075	0.16	8	-0.25	16	24
mol:PI-3-4-5-P3	0	0.002	-10000	0	-10000	0	0
cell proliferation	-0.001	0.19	-10000	0	-0.59	37	37
FOS	0.003	0.16	-10000	0	-0.42	54	54
NRAS	0.001	0.076	-10000	0	-0.58	10	10
mol:Ca2+	-0.01	0.1	0.22	5	-0.45	3	8
MAPK3	0.004	0.16	-10000	0	-0.51	30	30
MAPK1	0.004	0.15	-10000	0	-0.48	33	33
JAK2	-0.01	0.11	-10000	0	-0.43	10	10
NF2	-0.001	0.004	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.009	0.092	-10000	0	-0.28	50	50
NRG1	-0.067	0.19	-10000	0	-0.53	87	87
GRB2/SOS1	0.016	0.018	-10000	0	-0.42	1	1
MAPK8	0.001	0.096	0.2	5	-0.29	14	19
MAPK9	0.008	0.058	-10000	0	-0.25	4	4
ERBB2	0.005	0.085	0.39	19	-0.34	13	32
ERBB3	0.01	0.024	-10000	0	-0.58	1	1
SHC1	0.011	0.001	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
apoptosis	-0.002	0.035	0.82	1	-10000	0	1
STAT3 (dimer)	0.014	0.044	-10000	0	-1	1	1
RNF41	0.016	0.034	-10000	0	-0.32	6	6
FRAP1	0.007	0.016	-10000	0	-0.37	1	1
RAC1-CDC42/GTP	-0.027	0.065	-10000	0	-0.33	7	7
ErbB2/ErbB2/HSP90 (dimer)	0.008	0.061	0.26	18	-0.28	13	31
CHRNA1	-0.002	0.18	-10000	0	-0.6	35	35
myelination	0.006	0.086	-10000	0	-0.4	4	4
PPP3CB	-0.002	0.093	-10000	0	-0.4	3	3
KRAS	0.006	0.057	-10000	0	-0.56	6	6
RAC1-CDC42/GDP	-0.001	0.084	-10000	0	-0.31	5	5
NRG2	-0.017	0.1	-10000	0	-0.46	32	32
mol:GDP	-0.009	0.092	-10000	0	-0.28	50	50
SOS1	0.01	0.024	-10000	0	-0.58	1	1
MAP2K2	0.013	0.1	-10000	0	-0.4	10	10
SRC	0.01	0.024	-10000	0	-0.58	1	1
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.005	0.1	-10000	0	-0.42	5	5
MAP2K1	0	0.15	-10000	0	-0.53	17	17
heart morphogenesis	-0.01	0.1	0.22	5	-0.45	3	8
RAS family/GDP	-0.001	0.096	-10000	0	-0.42	7	7
GRB2	0.011	0.001	-10000	0	-10000	0	0
PRKACA	-0.003	0.006	-10000	0	-10000	0	0
CHRNE	0	0.056	-10000	0	-0.18	49	49
HSP90AA1	0.01	0.024	-10000	0	-0.58	1	1
activation of caspase activity	-0.008	0.018	0.44	1	-10000	0	1
nervous system development	-0.01	0.1	0.22	5	-0.45	3	8
CDC42	0.006	0.054	-10000	0	-0.58	5	5

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.012	0.046	-10000	0	-0.34	10	10
MAP4K4	0.019	0.065	-10000	0	-0.51	2	2
BAG4	0.009	0.034	-10000	0	-0.58	2	2
PKC zeta/ceramide	-0.023	0.041	0.15	1	-0.2	2	3
NFKBIA	0.011	0	-10000	0	-10000	0	0
BIRC3	-0.016	0.12	-10000	0	-0.52	30	30
BAX	-0.009	0.023	-10000	0	-0.31	1	1
RIPK1	0.011	0	-10000	0	-10000	0	0
AKT1	0.018	0.023	-10000	0	-0.51	1	1
BAD	-0.024	0.041	0.16	1	-0.2	2	3
SMPD1	0.012	0.046	-10000	0	-0.2	22	22
RB1	-0.034	0.067	0.16	2	-0.32	20	22
FADD/Caspase 8	0.028	0.062	-10000	0	-0.5	1	1
MAP2K4	-0.021	0.052	-10000	0	-0.31	9	9
NSMAF	0.011	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.018	0.041	-10000	0	-0.31	2	2
EGF	-0.18	0.25	-10000	0	-0.51	216	216
mol:ceramide	-0.032	0.043	0.14	9	-10000	0	9
MADD	0.011	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.014	0.038	-10000	0	-0.33	7	7
ASAH1	0.011	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.034	0.066	0.16	2	-0.32	20	22
cell proliferation	-0.036	0.09	-10000	0	-0.26	57	57
BID	0.009	0.047	-10000	0	-0.33	2	2
MAP3K1	-0.026	0.05	0.16	2	-0.33	6	8
EIF2A	-0.021	0.063	-10000	0	-0.32	17	17
TRADD	0.011	0	-10000	0	-10000	0	0
CRADD	0.01	0.024	-10000	0	-0.58	1	1
MAPK3	-0.009	0.039	-10000	0	-0.28	2	2
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.009	0.039	-10000	0	-0.28	2	2
Cathepsin D/ceramide	-0.024	0.041	-10000	0	-0.23	2	2
FADD	0.02	0.062	-10000	0	-0.52	1	1
KSR1	-0.024	0.044	0.16	2	-0.33	2	4
MAPK8	-0.016	0.045	0.15	1	-0.22	9	10
PRKRA	-0.024	0.04	0.16	2	-0.2	1	3
PDGFA	0.006	0.052	-10000	0	-0.47	7	7
TRAF2	0.01	0.024	-10000	0	-0.58	1	1
IGF1	-0.073	0.2	-10000	0	-0.52	94	94
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.032	0.042	0.14	9	-10000	0	9
CTSD	0.009	0.036	-10000	0	-0.5	3	3
regulation of nitric oxide biosynthetic process	0.016	0.018	-10000	0	-0.42	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.037	0.096	-10000	0	-0.28	57	57
PRKCD	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.031	-10000	0	-0.52	2	2
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.014	0.038	-10000	0	-0.33	7	7
RelA/NF kappa B1	0.016	0.018	-10000	0	-0.42	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.01	0.024	-10000	0	-0.58	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.015	0.066	-10000	0	-0.56	1	1
TNFR1A/BAG4/TNF-alpha	0.004	0.08	-10000	0	-0.33	32	32
mol:Sphingosine-1-phosphate	0.012	0.046	-10000	0	-0.34	10	10
MAP2K1	-0.012	0.041	-10000	0	-0.29	3	3
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.011	0	-10000	0	-10000	0	0
CYCS	-0.016	0.049	0.16	8	-0.23	13	21
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
NFKB1	0.01	0.024	-10000	0	-0.58	1	1
TNFR1A/BAG4	0.015	0.025	-10000	0	-0.42	2	2
EIF2AK2	-0.026	0.061	-10000	0	-0.3	19	19
TNF-alpha/TNFR1A/FAN	0.006	0.077	-10000	0	-0.32	30	30
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.023	0.047	-10000	0	-0.38	3	3
MAP2K2	-0.012	0.039	-10000	0	-0.29	2	2
SMPD3	0.006	0.071	-10000	0	-0.35	14	14
TNF	-0.017	0.12	-10000	0	-0.54	30	30
PKC zeta/PAR4	0.015	0.029	-10000	0	-0.39	3	3
mol:PHOSPHOCHOLINE	0.058	0.094	0.18	208	-10000	0	208
NF kappa B1/RelA/I kappa B alpha	0.032	0.029	-10000	0	-0.37	3	3
AIFM1	-0.01	0.038	0.16	8	-0.26	1	9
BCL2	-0.008	0.1	-10000	0	-0.55	20	20

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.007	0.048	-10000	0	-0.58	4	4
HDAC4	0.011	0.019	-10000	0	-0.46	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.006	0.09	0.36	36	-10000	0	36
CDKN1A	0.007	0.068	-10000	0	-0.58	5	5
KAT2B	-0.006	0.099	-10000	0	-0.58	17	17
BAX	0.01	0.024	-10000	0	-0.58	1	1
FOXO3	0.004	0.041	0.49	4	-10000	0	4
FOXO1	0.009	0.034	-10000	0	-0.58	2	2
FOXO4	0.016	0.029	-10000	0	-0.3	5	5
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.011	0	-10000	0	-10000	0	0
TAT	-0.018	0.11	-10000	0	-0.46	33	33
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.004	0.075	-10000	0	-0.42	19	19
PPARGC1A	-0.045	0.17	-10000	0	-0.56	58	58
FHL2	0.009	0.034	-10000	0	-0.58	2	2
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.011	0.041	-10000	0	-0.42	5	5
HIST2H4A	-0.006	0.09	-10000	0	-0.36	36	36
SIRT1/FOXO3a	0	0.032	0.29	2	-0.36	3	5
SIRT1	0.004	0.055	-10000	0	-0.58	5	5
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.017	0.04	-10000	0	-0.34	7	7
SIRT1/Histone H1b	0.003	0.067	-10000	0	-0.3	20	20
apoptosis	-0.017	0.038	0.35	6	-10000	0	6
SIRT1/PGC1A	-0.035	0.11	-10000	0	-0.35	63	63
p53/SIRT1	-0.041	0.13	0.4	2	-0.43	59	61
SIRT1/FOXO4	0.014	0.048	-10000	0	-0.37	8	8
FOXO1/FHL2/SIRT1	0.015	0.043	-10000	0	-0.32	9	9
HIST1H1E	0.003	0.062	-10000	0	-0.31	17	17
SIRT1/p300	0.008	0.061	-10000	0	-0.52	7	7
muscle cell differentiation	0	0.08	0.41	19	-10000	0	19
TP53	-0.047	0.17	-10000	0	-0.58	56	56
KU70/SIRT1/BAX	0.017	0.038	-10000	0	-0.35	6	6
CREBBP	0.011	0	-10000	0	-10000	0	0
MEF2D	0.01	0.024	-10000	0	-0.58	1	1
HIV-1 Tat/SIRT1	-0.011	0.085	-10000	0	-0.33	38	38
ACSS2	0.012	0.044	-10000	0	-0.42	6	6
SIRT1/PCAF/MYOD	0	0.08	-10000	0	-0.41	19	19

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.011	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	0.013	0.073	-9999	-0.44	2	2
Syndecan-3/Neurocan	0.004	0.041	-9999	-0.6	1	1
POMC	-0.026	0.14	-9999	-0.52	42	42
EGFR	0.004	0.063	-9999	-0.53	8	8
Syndecan-3/EGFR	0.016	0.042	-9999	-0.34	6	6
AGRP	-0.001	0.05	-9999	-0.46	7	7
NCSTN	0.011	0	-9999	-10000	0	0
PSENEN	0.01	0.024	-9999	-0.58	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.006	0.054	-9999	-0.58	5	5
APH1A	0.011	0	-9999	-10000	0	0
NCAN	-0.004	0.065	-9999	-0.46	12	12
long-term memory	0.022	0.041	-9999	-0.34	6	6
Syndecan-3/IL8	-0.041	0.12	-9999	-0.3	67	67
PSEN1	0.011	0	-9999	-10000	0	0
Src/Cortactin	0.016	0.018	-9999	-0.42	1	1
FYN	0.005	0.06	-9999	-0.55	7	7
limb bud formation	-0.002	0.026	-9999	-0.62	1	1
MC4R	-0.004	0.056	-9999	-0.46	9	9
SRC	0.01	0.024	-9999	-0.58	1	1
PTN	-0.025	0.14	-9999	-0.54	39	39
FGFR/FGF/Syndecan-3	-0.002	0.026	-9999	-0.63	1	1
neuron projection morphogenesis	-0.005	0.073	-9999	-0.43	2	2
Syndecan-3/AgRP	0.003	0.036	-9999	-0.6	1	1
Syndecan-3/AgRP/MC4R	-0.004	0.044	-9999	-0.5	2	2
Fyn/Cortactin	0.012	0.044	-9999	-0.39	7	7
SDC3	-0.002	0.027	-9999	-0.64	1	1
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.041	0.12	-9999	-0.3	67	67
IL8	-0.11	0.22	-9999	-0.52	133	133
Syndecan-3/Fyn/Cortactin	0.023	0.042	-9999	-0.35	6	6
Syndecan-3/CASK	-0.002	0.025	-9999	-0.6	1	1
alpha-MSH/MC4R	-0.022	0.11	-9999	-0.38	48	48
Gamma Secretase	0.031	0.033	-9999	-0.29	6	6

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.014	0.022	-9999	-0.36	2	2
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.011	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.001	0.076	-9999	-0.58	10	10
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.008	0.042	-9999	-0.58	3	3
RAC1-CDC42/GTP/PAK family	0.016	0.035	-9999	-0.29	5	5
response to UV	0	0	-9999	-10000	0	0
YES1	0.004	0.064	-9999	-0.58	7	7
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.009	0.034	-9999	-0.58	2	2
FYN	0.005	0.06	-9999	-0.55	7	7
MAP3K12	0.003	0.068	-9999	-0.54	9	9
FGR	-0.026	0.14	-9999	-0.54	40	40
p38 alpha/TAB1	-0.038	0.087	-9999	-0.34	30	30
PRKG1	-0.024	0.14	-9999	-0.56	37	37
DUSP8	0.007	0.048	-9999	-0.58	4	4
PGK/cGMP/p38 alpha	-0.05	0.11	-9999	-0.36	48	48
apoptosis	-0.037	0.083	-9999	-0.33	30	30
RAL/GTP	0.015	0	-9999	-10000	0	0
LYN	0.011	0	-9999	-10000	0	0
DUSP1	-0.007	0.092	-9999	-0.47	22	22
PAK1	0.011	0	-9999	-10000	0	0
SRC	0.01	0.024	-9999	-0.58	1	1
RAC1/OSM/MEKK3/MKK3	0.027	0.034	-9999	-0.37	4	4
TRAF6	0.01	0.024	-9999	-0.58	1	1
RAC1	0.011	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.01	0.031	-9999	-0.52	2	2
RAC1-CDC42/GTP	0.012	0.034	-9999	-0.36	5	5
MAPK11	-0.024	0.14	-9999	-0.42	44	44
BLK	-0.12	0.23	-9999	-0.52	139	139
HCK	-0.018	0.12	-9999	-0.55	31	31
MAP2K3	0.01	0.024	-9999	-0.58	1	1
DUSP16	0.011	0	-9999	-10000	0	0
DUSP10	0.009	0.039	-9999	-0.54	3	3
TRAF6/MEKK3	0.013	0.024	-9999	-0.33	3	3
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	-0.009	0.11	-9999	-0.37	30	30
positive regulation of innate immune response	-0.021	0.15	-9999	-0.46	39	39
LCK	-0.031	0.14	-9999	-0.51	48	48
p38alpha-beta/MKP7	-0.014	0.14	-9999	-0.45	36	36
p38alpha-beta/MKP5	-0.015	0.15	-9999	-0.46	37	37
PGK/cGMP	-0.018	0.1	-9999	-0.41	37	37
PAK2	0.01	0.024	-9999	-0.58	1	1
p38alpha-beta/MKP1	-0.022	0.15	-9999	-0.44	42	42
CDC42	0.006	0.054	-9999	-0.58	5	5
RALB	0.011	0	-9999	-10000	0	0
RALA	0.011	0	-9999	-10000	0	0
PAK3	0	0.057	-9999	-0.46	9	9

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.003	0.084	-9999	-0.48	18	18
PLK4	0.009	0.034	-9999	-0.58	2	2
regulation of centriole replication	0.006	0.069	-9999	-0.36	19	19

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.019	0.12	-9999	-0.4	15	15
positive regulation of NF-kappaB transcription factor activity	0	0.002	-9999	-10000	0	0
CRKL	0.011	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.003	0.12	-9999	-0.54	12	12
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0.078	-9999	-0.37	22	22
antigen processing and presentation of peptide antigen via MHC class I	-0.038	0.074	-9999	-0.29	18	18
CaM/Ca2+	-0.018	0.11	-9999	-0.47	8	8
RAP1A	0.01	0.024	-9999	-0.58	1	1
STAT1 (dimer)/SHP2	-0.012	0.12	-9999	-0.53	11	11
AKT1	-0.003	0.11	-9999	-0.46	12	12
MAP2K1	-0.01	0.12	-9999	-0.55	11	11
MAP3K11	-0.014	0.11	-9999	-0.45	9	9
IFNGR1	0.008	0.012	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.051	0.12	-9999	-0.48	30	30
Rap1/GTP	-0.031	0.073	-9999	-0.4	6	6
CRKL/C3G	0.016	0.018	-9999	-0.42	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.021	0.12	-9999	-0.44	13	13
CEBPB	-0.008	0.16	-9999	-0.47	35	35
STAT3	0.011	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.053	0.22	-9999	-0.83	29	29
STAT1	-0.013	0.12	-9999	-0.52	11	11
CALM1	0.011	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.065	0.18	-9999	-0.51	86	86
PIK3CA	0.009	0.034	-9999	-0.58	2	2
STAT1 (dimer)/PIAS1	-0.005	0.11	-9999	-0.49	11	11
CEBPB/PTGES2/Cbp/p300	-0.039	0.086	-9999	-0.4	15	15
mol:Ca2+	-0.021	0.11	-9999	-0.4	15	15
MAPK3	-0.005	0.13	-9999	-0.68	8	8
STAT1 (dimer)	-0.05	0.1	-9999	-0.4	18	18
MAPK1	-0.005	0.12	-9999	-0.56	12	12
JAK2	-0.011	0.1	-9999	-0.56	21	21
PIK3R1	0.008	0.042	-9999	-0.58	3	3
JAK1	0.005	0.044	-9999	-0.6	3	3
CAMK2D	0.007	0.048	-9999	-0.58	4	4
DAPK1	-0.012	0.16	-9999	-0.54	37	37
SMAD7	0.012	0.059	-9999	-0.29	2	2
CBL/CRKL/C3G	-0.002	0.1	-9999	-0.49	5	5
PI3K	-0.041	0.1	-9999	-0.5	12	12
IFNG	-0.066	0.18	-9999	-0.51	86	86
apoptosis	-0.012	0.12	-9999	-0.4	35	35
CAMK2G	0.011	0	-9999	-10000	0	0
STAT3 (dimer)	0.011	0	-9999	-10000	0	0
CAMK2A	-0.019	0.12	-9999	-0.53	33	33
CAMK2B	-0.054	0.17	-9999	-0.49	76	76
FRAP1	-0.003	0.1	-9999	-0.42	12	12
PRKCD	-0.002	0.11	-9999	-0.46	12	12
RAP1B	0.011	0	-9999	-10000	0	0
negative regulation of cell growth	-0.038	0.074	-9999	-0.29	18	18
PTPN2	0.008	0.042	-9999	-0.58	3	3
EP300	0.008	0.048	-9999	-0.58	4	4
IRF1	0.001	0.12	-9999	-0.49	15	15
STAT1 (dimer)/PIASy	-0.005	0.11	-9999	-0.5	10	10
SOCS1	-0.047	0.22	-9999	-1.4	14	14
mol:GDP	-0.03	0.086	-9999	-0.41	8	8
CASP1	0.002	0.086	-9999	-0.28	35	35
PTGES2	0.007	0.045	-9999	-0.48	5	5
IRF9	0.02	0.054	-9999	-0.23	4	4
mol:PI-3-4-5-P3	-0.04	0.099	-9999	-0.48	12	12
RAP1/GDP	-0.031	0.073	-9999	-0.43	5	5
CBL	-0.012	0.11	-9999	-0.47	8	8
MAP3K1	-0.016	0.12	-9999	-0.54	11	11
PIAS1	0.011	0	-9999	-10000	0	0
PIAS4	0.011	0.024	-9999	-0.56	1	1
antigen processing and presentation of peptide antigen via MHC class II	-0.038	0.074	-9999	-0.29	18	18
PTPN11	-0.019	0.11	-9999	-0.4	15	15
CREBBP	0.012	0.001	-9999	-10000	0	0
RAPGEF1	0.01	0.024	-9999	-0.58	1	1

×

PDGFR-beta signaling 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
S1P1/Sphingosine-1-phosphate	-0.014	0.12	-9999	-0.41	38	38
PDGFB-D/PDGFRB/SLAP	-0.012	0.11	-9999	-0.41	41	41
PDGFB-D/PDGFRB/APS/CBL	-0.003	0.09	-9999	-0.34	29	29
AKT1	0.031	0.066	-9999	-0.48	3	3
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.015	0.13	-9999	-0.48	27	27
PIK3CA	0.009	0.034	-9999	-0.58	2	2
FGR	-0.041	0.16	-9999	-0.57	39	39
mol:Ca2+	-0.005	0.11	-9999	-0.58	16	16
MYC	0	0.12	-9999	-0.58	16	16
SHC1	0.011	0	-9999	-10000	0	0
HRAS/GDP	0.017	0.066	-9999	-0.32	17	17
LRP1/PDGFRB/PDGFB	0.007	0.081	-9999	-0.39	20	20
GRB10	0.007	0.048	-9999	-0.58	4	4
PTPN11	0.006	0.054	-9999	-0.58	5	5
GO:0007205	-0.006	0.11	-9999	-0.59	16	16
PTEN	0.005	0.059	-9999	-0.58	6	6
GRB2	0.011	0	-9999	-10000	0	0
GRB7	0.002	0.066	-9999	-0.46	12	12
PDGFB-D/PDGFRB/SHP2	0.001	0.078	-9999	-0.4	22	22
PDGFB-D/PDGFRB/GRB10	0.002	0.076	-9999	-0.39	21	21
cell cycle arrest	-0.012	0.11	-9999	-0.4	41	41
HRAS	0.008	0.041	-9999	-0.49	4	4
HIF1A	0.032	0.077	-9999	-0.5	7	7
GAB1	-0.016	0.13	-9999	-0.6	18	18
mol:GTP	0	0	-9999	-10000	0	0
DNM2	-0.011	0.12	-9999	-0.5	22	22
PDGFB-D/PDGFRB	0.012	0.068	-9999	-0.34	21	21
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.005	0.068	-9999	-0.38	17	17
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.039	0.12	-9999	-0.42	40	40
positive regulation of MAPKKK cascade	0.001	0.078	-9999	-0.39	22	22
PIK3R1	0.008	0.042	-9999	-0.58	3	3
mol:IP3	-0.006	0.11	-9999	-0.6	16	16
E5	0	0.002	-9999	-10000	0	0
CSK	0.01	0.024	-9999	-0.58	1	1
PDGFB-D/PDGFRB/GRB7	-0.001	0.084	-9999	-0.37	28	28
SHB	0.011	0.019	-9999	-0.46	1	1
BLK	-0.098	0.21	-9999	-0.56	88	88
PTPN2	0.008	0.042	-9999	-0.58	3	3
PDGFB-D/PDGFRB/SNX15	0.005	0.068	-9999	-0.38	17	17
BCAR1	0.008	0.044	-9999	-0.52	4	4
VAV2	-0.019	0.14	-9999	-0.56	26	26
CBL	0.011	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.004	0.07	-9999	-0.39	18	18
LCK	-0.037	0.13	-9999	-0.5	37	37
PDGFRB	-0.004	0.093	-9999	-0.54	17	17
ACP1	0.011	0	-9999	-10000	0	0
HCK	-0.033	0.15	-9999	-0.57	35	35
ABL1	-0.016	0.12	-9999	-0.5	23	23
PDGFB-D/PDGFRB/CBL	-0.018	0.14	-9999	-0.6	21	21
PTPN1	0.01	0.025	-9999	-0.59	1	1
SNX15	0.011	0	-9999	-10000	0	0
STAT3	0.011	0	-9999	-10000	0	0
STAT1	0.006	0.051	-9999	-0.5	6	6
cell proliferation	0.002	0.11	-9999	-0.49	18	18
SLA	-0.013	0.11	-9999	-0.52	27	27
actin cytoskeleton reorganization	0.026	0.067	-9999	-0.5	3	3
SRC	-0.012	0.068	-9999	-0.39	16	16
PI3K	-0.013	0.059	-9999	-0.52	2	2
PDGFB-D/PDGFRB/GRB7/SHC	0.007	0.071	-9999	-0.38	11	11
SH2B2	-0.014	0.11	-9999	-0.52	29	29
PLCgamma1/SPHK1	-0.016	0.13	-9999	-0.5	27	27
LYN	-0.01	0.065	-9999	-0.38	15	15
LRP1	0.006	0.057	-9999	-0.56	6	6
SOS1	0.01	0.024	-9999	-0.58	1	1
STAT5B	0.011	0	-9999	-10000	0	0
STAT5A	0.011	0	-9999	-10000	0	0
NCK1-2/p130 Cas	-0.001	0.064	-9999	-0.42	4	4
SPHK1	-0.03	0.14	-9999	-0.51	47	47
EDG1	0	0.003	-9999	-10000	0	0
mol:DAG	-0.006	0.11	-9999	-0.6	16	16
PLCG1	-0.006	0.12	-9999	-0.62	16	16
NHERF/PDGFRB	0.012	0.06	-9999	-0.35	13	13
YES1	-0.018	0.099	-9999	-0.5	19	19
cell migration	0.012	0.059	-9999	-0.35	13	13
SHC/Grb2/SOS1	0.002	0.054	-9999	-0.3	2	2
SLC9A3R2	0.01	0.024	-9999	-0.58	1	1
SLC9A3R1	0.011	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.016	0.064	-9999	-0.32	18	18
FYN	-0.015	0.087	-9999	-0.45	19	19
DOK1	0.015	0.06	-9999	-0.32	15	15
HRAS/GTP	0.006	0.03	-9999	-0.35	4	4
PDGFB	0.007	0.048	-9999	-0.51	5	5
RAC1	-0.009	0.14	-9999	-0.6	21	21
PRKCD	0.015	0.061	-9999	-0.33	15	15
FER	0.01	0.077	-9999	-0.36	19	19
MAPKKK cascade	-0.009	0.049	-9999	-10000	0	0
RASA1	0.014	0.066	-9999	-0.35	16	16
NCK1	0.009	0.034	-9999	-0.58	2	2
NCK2	0.01	0.024	-9999	-0.58	1	1
p62DOK/Csk	0.021	0.057	-9999	-0.29	1	1
PDGFB-D/PDGFRB/SHB	0.005	0.069	-9999	-0.38	18	18
chemotaxis	-0.016	0.12	-9999	-0.48	24	24
STAT1-3-5/STAT1-3-5	-0.01	0.053	-9999	-0.55	1	1
Bovine Papilomavirus E5/PDGFRB	-0.003	0.068	-9999	-0.4	17	17
PTPRJ	0.01	0.024	-9999	-0.58	1	1

×

S1P4 pathway

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
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.046	0.16	-9999	-0.49	68	68
CDC42/GTP	-0.017	0.11	-9999	-0.44	14	14
PLCG1	-0.015	0.11	-9999	-0.45	14	14
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.011	0	-9999	-10000	0	0
GNAI3	0.011	0	-9999	-10000	0	0
G12/G13	0.015	0.025	-9999	-0.42	2	2
cell migration	-0.017	0.1	-9999	-0.43	14	14
S1PR5	0	0.076	-9999	-0.53	12	12
S1PR4	-0.024	0.14	-9999	-0.53	39	39
MAPK3	-0.015	0.11	-9999	-0.46	14	14
MAPK1	-0.015	0.11	-9999	-0.46	14	14
S1P/S1P5/Gi	-0.012	0.096	-9999	-0.53	6	6
GNAI1	-0.003	0.089	-9999	-0.56	15	15
CDC42/GDP	0.005	0.04	-9999	-0.43	5	5
S1P/S1P5/G12	0.009	0.048	-9999	-0.32	12	12
RHOA	0.005	0.075	-9999	-0.3	27	27
S1P/S1P4/Gi	-0.022	0.11	-9999	-0.49	13	13
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.012	0.11	-9999	-0.55	25	25
S1P/S1P4/G12/G13	0.001	0.08	-9999	-0.32	26	26
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.009	0.034	-9999	-0.58	2	2
CDC42	0.006	0.054	-9999	-0.58	5	5

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.022	0.022	-9999	-0.35	2	2
SNTA1	0.006	0.055	-9999	-0.54	6	6
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.013	0.066	-9999	-0.38	16	16
MAPK12	-0.003	0.093	-9999	-0.37	23	23
CCND1	0.006	0.042	-9999	-0.22	8	8
p38 gamma/SNTA1	0	0.094	-9999	-0.37	22	22
MAP2K3	0.01	0.024	-9999	-0.58	1	1
PKN1	0.008	0.042	-9999	-0.58	3	3
G2/M transition checkpoint	-0.003	0.093	-9999	-0.36	23	23
MAP2K6	0.009	0.059	-9999	-0.32	18	18
MAPT	-0.024	0.11	-9999	-0.33	52	52
MAPK13	0.017	0.025	-9999	-0.42	2	2
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.009	0.042	-9999	-0.35	8	8

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.001	0.083	0.58	12	-10000	0	12
PI3K Class IB/PDE3B	-0.001	0.083	-10000	0	-0.58	12	12
PDE3B	-0.001	0.083	-10000	0	-0.58	12	12

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0.018	-9999	-0.43	1	1
SMARCC1	0.002	0.019	-9999	-0.42	1	1
REL	0.011	0.043	-9999	-0.58	3	3
HDAC7	0.027	0.093	-9999	-0.51	8	8
JUN	0.004	0.052	-9999	-0.56	5	5
EP300	0.007	0.048	-9999	-0.58	4	4
KAT2B	-0.006	0.099	-9999	-0.58	17	17
KAT5	0.011	0.024	-9999	-0.58	1	1
MAPK14	0.011	0.06	-9999	-0.44	10	10
FOXO1	0.009	0.034	-9999	-0.58	2	2
T-DHT/AR	0.024	0.098	-9999	-0.52	9	9
MAP2K6	0.001	0.078	-9999	-0.59	10	10
BRM/BAF57	0.009	0.041	-9999	-0.43	5	5
MAP2K4	0.008	0.042	-9999	-0.58	3	3
SMARCA2	0.005	0.049	-9999	-0.59	4	4
PDE9A	-0.082	0.29	-9999	-1.1	44	44
NCOA2	0.003	0.067	-9999	-0.56	8	8
CEBPA	-0.005	0.098	-9999	-0.57	17	17
EHMT2	0.007	0.031	-9999	-0.52	2	2
cell proliferation	0.022	0.12	-9999	-0.48	18	18
NR0B1	-0.001	0.05	-9999	-0.46	7	7
EGR1	-0.011	0.1	-9999	-0.5	24	24
RXRs/9cRA	0.004	0.054	-9999	-0.27	6	6
AR/RACK1/Src	0.016	0.075	-9999	-0.42	8	8
AR/GR	-0.01	0.1	-9999	-0.35	33	33
GNB2L1	0.011	0.019	-9999	-0.46	1	1
PKN1	0.008	0.042	-9999	-0.58	3	3
RCHY1	0.01	0.024	-9999	-0.58	1	1
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.016	0.037	-9999	-0.42	4	4
T-DHT/AR/TIF2/CARM1	0.02	0.085	-9999	-0.43	11	11
SRC	0.024	0.06	-9999	-0.39	7	7
NR3C1	-0.014	0.12	-9999	-0.54	28	28
KLK3	-0.2	0.37	-9999	-1.1	70	70
APPBP2	0.008	0.049	-9999	-0.58	4	4
TRIM24	0.009	0.006	-9999	-10000	0	0
T-DHT/AR/TIP60	0.018	0.077	-9999	-0.48	8	8
TMPRSS2	-0.025	0.14	-9999	-0.88	9	9
RXRG	-0.013	0.094	-9999	-0.46	25	25
mol:9cRA	-0.001	0.002	-9999	-10000	0	0
RXRA	0.01	0.024	-9999	-0.58	1	1
RXRB	0.011	0.001	-9999	-10000	0	0
CARM1	0.01	0.024	-9999	-0.58	1	1
NR2C2	0.01	0.024	-9999	-0.58	1	1
KLK2	0.016	0.1	-9999	-0.66	3	3
AR	0	0.083	-9999	-0.29	28	28
SENP1	0.01	0.024	-9999	-0.58	1	1
HSP90AA1	0.01	0.024	-9999	-0.58	1	1
MDM2	0.012	0.045	-9999	-0.52	4	4
SRY	0.002	0.038	-9999	-0.45	4	4
GATA2	-0.018	0.13	-9999	-0.56	31	31
MYST2	0.011	0.024	-9999	-0.58	1	1
HOXB13	-0.097	0.21	-9999	-0.5	123	123
T-DHT/AR/RACK1/Src	0.022	0.073	-9999	-0.42	8	8
positive regulation of transcription	-0.018	0.13	-9999	-0.56	31	31
DNAJA1	0.012	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.022	0.041	-9999	-0.47	3	3
NCOA1	0.011	0.027	-9999	-0.62	1	1
SPDEF	-0.15	0.25	-9999	-0.53	179	179
T-DHT/AR/TIF2	0.014	0.11	-9999	-0.75	6	6
T-DHT/AR/Hsp90	0.017	0.074	-9999	-0.43	10	10
GSK3B	0.009	0.034	-9999	-0.58	2	2
NR2C1	0.011	0.024	-9999	-0.58	1	1
mol:T-DHT	0.02	0.063	-9999	-0.37	13	13
SIRT1	0.006	0.054	-9999	-0.58	5	5
ZMIZ2	0.015	0.027	-9999	-0.58	1	1
POU2F1	0.01	0.077	-9999	-0.54	10	10
T-DHT/AR/DAX-1	0.009	0.075	-9999	-0.43	9	9
CREBBP	0.011	0.001	-9999	-10000	0	0
SMARCE1	0.008	0.025	-9999	-0.58	1	1

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.014	0.1	-10000	0	-0.52	12	12
UGCG	0.01	0.069	-10000	0	-0.84	3	3
AKT1/mTOR/p70S6K/Hsp90/TERT	0.01	0.13	-10000	0	-0.42	26	26
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.01	0.068	-10000	0	-0.82	3	3
mol:DAG	-0.001	0.009	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.039	0.11	-10000	0	-0.46	28	28
FRAP1	0.017	0.15	-10000	0	-0.54	28	28
FOXO3	0.024	0.13	-10000	0	-0.47	22	22
AKT1	0.018	0.14	-10000	0	-0.49	26	26
GAB2	0.01	0.034	-10000	0	-0.58	2	2
SMPD1	0.013	0.038	-10000	0	-0.6	1	1
SGMS1	0.014	0.028	-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	0.014	0.035	-10000	0	-0.36	5	5
CALM1	0.011	0	-10000	0	-10000	0	0
cell proliferation	0.019	0.081	-10000	0	-0.44	6	6
EIF3A	0.01	0.024	-10000	0	-0.58	1	1
PI3K	0.018	0.041	-10000	0	-0.42	5	5
RPS6KB1	0.008	0.096	-10000	0	-0.96	5	5
mol:sphingomyelin	-0.001	0.009	-10000	0	-10000	0	0
natural killer cell activation	0	0.001	-10000	0	-0.012	4	4
JAK3	0.003	0.077	-10000	0	-0.53	12	12
PIK3R1	0.011	0.042	-10000	0	-0.58	3	3
JAK1	0.011	0.042	-10000	0	-0.58	3	3
NFKB1	0.01	0.024	-10000	0	-0.58	1	1
MYC	0.021	0.15	-10000	0	-0.65	14	14
MYB	0.006	0.16	-10000	0	-1.2	10	10
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.012	0.14	-10000	0	-0.48	25	25
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.018	0.092	-10000	0	-0.87	5	5
mol:PI-3-4-5-P3	0.012	0.13	-10000	0	-0.46	25	25
Rac1/GDP	0.02	0.032	-10000	0	-0.32	5	5
T cell proliferation	0.017	0.13	-10000	0	-0.48	18	18
SHC1	0.012	0.002	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.003	0.009	-10000	0	-0.065	9	9
PRKCZ	0.016	0.13	-10000	0	-0.51	18	18
NF kappa B1 p50/RelA	-0.038	0.11	-10000	0	-0.48	23	23
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.007	0.11	-10000	0	-0.5	18	18
HSP90AA1	0.01	0.024	-10000	0	-0.58	1	1
RELA	0.011	0	-10000	0	-10000	0	0
IL2RA	-0.044	0.17	-10000	0	-0.55	60	60
IL2RB	-0.015	0.12	-10000	0	-0.55	30	30
TERT	-0.047	0.17	-10000	0	-0.52	66	66
E2F1	0.014	0.065	-10000	0	-0.4	13	13
SOS1	0.011	0.024	-10000	0	-0.58	1	1
RPS6	0.007	0.045	-10000	0	-0.48	5	5
mol:cAMP	-0.002	0.004	0.031	9	-10000	0	9
PTPN11	0.007	0.054	-10000	0	-0.58	5	5
IL2RG	0.001	0.084	-10000	0	-0.56	13	13
actin cytoskeleton organization	0.017	0.13	-10000	0	-0.48	18	18
GRB2	0.012	0.002	-10000	0	-10000	0	0
IL2	0.004	0.027	-10000	0	-0.45	2	2
PIK3CA	0.012	0.034	-10000	0	-0.58	2	2
Rac1/GTP	0.027	0.031	-10000	0	-0.3	5	5
LCK	-0.028	0.14	-10000	0	-0.51	48	48
BCL2	0.014	0.18	-10000	0	-0.85	18	18

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.009	0.034	-9999	-0.58	2	2
Caspase 8 (4 units)	0.006	0.086	-9999	-0.48	6	6
NEF	-0.013	0.05	-9999	-10000	0	0
NFKBIA	0.009	0.023	-9999	-10000	0	0
BIRC3	0.007	0.12	-9999	-0.52	30	30
CYCS	-0.001	0.11	-9999	-0.51	10	10
RIPK1	0.011	0	-9999	-10000	0	0
CD247	-0.035	0.16	-9999	-0.64	33	33
MAP2K7	0.013	0.083	-9999	-0.44	7	7
protein ubiquitination	0.038	0.057	-9999	-0.4	3	3
CRADD	0.01	0.024	-9999	-0.58	1	1
DAXX	0.011	0	-9999	-10000	0	0
FAS	0.002	0.073	-9999	-0.56	10	10
BID	0.001	0.097	-9999	-0.5	6	6
NF-kappa-B/RelA/I kappa B alpha	0.017	0.065	-9999	-0.29	17	17
TRADD	0.011	0	-9999	-10000	0	0
MAP3K5	0.009	0.034	-9999	-0.58	2	2
CFLAR	0.011	0	-9999	-10000	0	0
FADD	0.011	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.017	0.065	-9999	-0.29	17	17
MAPK8	0.018	0.082	-9999	-0.51	5	5
APAF1	0.008	0.042	-9999	-0.58	3	3
TRAF1	0.008	0.038	-9999	-0.46	4	4
TRAF2	0.01	0.024	-9999	-0.58	1	1
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.005	0.1	-9999	-0.3	45	45
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.032	0.057	-9999	-0.31	1	1
CHUK	0.039	0.061	-9999	-0.43	3	3
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.027	0.049	-9999	-0.32	10	10
TCRz/NEF	-0.04	0.16	-9999	-0.39	82	82
TNF	-0.017	0.12	-9999	-0.54	30	30
FASLG	-0.063	0.23	-9999	-0.61	80	80
NFKB1	0.008	0.033	-9999	-0.58	1	1
TNFR1A/BAG4/TNF-alpha	0.004	0.08	-9999	-0.33	32	32
CASP6	-0.017	0.058	-9999	-0.5	4	4
CASP7	0.022	0.13	-9999	-0.56	18	18
RELA	0.009	0.023	-9999	-10000	0	0
CASP2	0.011	0	-9999	-10000	0	0
CASP3	0.022	0.13	-9999	-0.55	19	19
TNFRSF1A	0.011	0	-9999	-10000	0	0
TNFR1A/BAG4	0.015	0.025	-9999	-0.42	2	2
CASP8	0.01	0.024	-9999	-0.58	1	1
CASP9	0.01	0.024	-9999	-0.58	1	1
MAP3K14	0.037	0.057	-9999	-0.42	1	1
APAF-1/Caspase 9	-0.038	0.1	-9999	-0.46	23	23
BCL2	0.015	0.094	-9999	-0.46	9	9

×

S1P3 pathway

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
PDGFRB	-0.004	0.092	-9999	-0.54	17	17
mol:S1P	0	0.005	-9999	-10000	0	0
S1P1/S1P/Gi	-0.009	0.089	-9999	-0.29	34	34
GNAO1	-0.046	0.16	-9999	-0.49	68	68
S1P/S1P3/G12/G13	0.018	0.041	-9999	-0.31	9	9
AKT1	0	0.097	-9999	-0.57	12	12
AKT3	-0.012	0.2	-9999	-1.1	15	15
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.004	0.092	-9999	-0.54	17	17
GNAI2	0.012	0.004	-9999	-10000	0	0
GNAI3	0.012	0.004	-9999	-10000	0	0
GNAI1	-0.002	0.09	-9999	-0.56	15	15
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.006	0.06	-9999	-0.54	7	7
S1PR2	0.011	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.009	0.11	-9999	-0.52	12	12
MAPK3	-0.003	0.11	-9999	-0.49	13	13
MAPK1	-0.003	0.11	-9999	-0.49	13	13
JAK2	-0.011	0.13	-9999	-0.46	24	24
CXCR4	-0.016	0.13	-9999	-0.5	23	23
FLT1	0.008	0.053	-9999	-0.56	5	5
RhoA/GDP	0.008	0.018	-9999	-0.43	1	1
Rac1/GDP	0.008	0	-9999	-10000	0	0
SRC	-0.003	0.11	-9999	-0.49	12	12
S1P/S1P3/Gi	-0.009	0.11	-9999	-0.52	12	12
RAC1	0.011	0	-9999	-10000	0	0
RhoA/GTP	-0.004	0.1	-9999	-0.48	12	12
VEGFA	0.012	0.02	-9999	-0.45	1	1
S1P/S1P2/Gi	-0.006	0.091	-9999	-0.42	8	8
VEGFR1 homodimer/VEGFA homodimer	0.018	0.043	-9999	-0.39	6	6
RHOA	0.01	0.024	-9999	-0.58	1	1
S1P/S1P3/Gq	0.001	0.097	-9999	-0.34	36	36
GNAQ	0.005	0.059	-9999	-0.58	6	6
GNAZ	-0.012	0.11	-9999	-0.55	25	25
G12/G13	0.015	0.025	-9999	-0.42	2	2
GNA14	-0.007	0.1	-9999	-0.56	19	19
GNA15	-0.008	0.1	-9999	-0.54	21	21
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.009	0.034	-9999	-0.58	2	2
GNA11	0.007	0.05	-9999	-0.53	5	5
Rac1/GTP	-0.003	0.1	-9999	-0.48	12	12

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.023	0.047	-10000	0	-0.37	6	6
HDAC3	0.011	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.013	0.075	-10000	0	-0.4	19	19
GATA1/HDAC4	0.005	0.055	-10000	0	-0.32	16	16
GATA1/HDAC5	0.004	0.058	-10000	0	-0.33	17	17
GATA2/HDAC5	-0.006	0.098	-10000	0	-0.41	32	32
HDAC5/BCL6/BCoR	0.02	0.03	-10000	0	-0.28	6	6
HDAC9	-0.038	0.16	-10000	0	-0.54	53	53
Glucocorticoid receptor/Hsp90/HDAC6	0.006	0.075	-10000	0	-0.32	29	29
HDAC4/ANKRA2	0.016	0.023	-10000	0	-0.37	2	2
HDAC5/YWHAB	0.016	0.023	-10000	0	-0.37	2	2
NPC/RanGAP1/SUMO1/Ubc9	-0.001	0.095	-10000	0	-0.43	24	24
GATA2	-0.018	0.13	-10000	0	-0.56	31	31
HDAC4/RFXANK	0.014	0.032	-10000	0	-0.37	4	4
BCOR	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.008	0.046	-10000	0	-0.55	4	4
HDAC5	0.01	0.031	-10000	0	-0.52	2	2
GNB1/GNG2	0.012	0.046	-10000	0	-0.38	8	8
Histones	0.011	0.081	-10000	0	-1.2	1	1
ADRBK1	0.01	0.031	-10000	0	-0.52	2	2
HDAC4	0.011	0.019	-10000	0	-0.46	1	1
XPO1	0	0.08	-10000	0	-0.58	11	11
HDAC5/ANKRA2	0.015	0.029	-10000	0	-0.39	3	3
HDAC4/Ubc9	0.016	0.014	-10000	0	-0.32	1	1
HDAC7	0.01	0.024	-10000	0	-0.58	1	1
HDAC5/14-3-3 E	0.016	0.023	-10000	0	-0.37	2	2
TUBA1B	0.011	0	-10000	0	-10000	0	0
HDAC6	0.011	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.014	0.042	-10000	0	-0.46	4	4
CAMK4	-0.012	0.11	-10000	0	-0.55	25	25
Tubulin/HDAC6	0.004	0.075	-10000	0	-0.29	36	36
SUMO1	-0.008	0.1	-10000	0	-0.58	19	19
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.011	0	-10000	0	-10000	0	0
GATA1	-0.005	0.074	-10000	0	-0.46	15	15
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.011	0	-10000	0	-10000	0	0
NR3C1	-0.014	0.12	-10000	0	-0.54	28	28
SUMO1/HDAC4	0.005	0.1	-10000	0	-0.55	19	19
SRF	0.01	0.027	-10000	0	-0.46	2	2
HDAC4/YWHAB	0.016	0.014	-10000	0	-0.32	1	1
Tubulin	-0.005	0.088	-10000	0	-0.35	36	36
HDAC4/14-3-3 E	0.016	0.014	-10000	0	-0.32	1	1
GNB1	0.011	0	-10000	0	-10000	0	0
RANGAP1	0.01	0.031	-10000	0	-0.52	2	2
BCL6/BCoR	0.015	0.027	-10000	0	-0.32	4	4
HDAC4/HDAC3/SMRT (N-CoR2)	0.02	0.031	-10000	0	-0.32	5	5
HDAC4/SRF	0.007	0.075	-10000	0	-0.33	27	27
HDAC4/ER alpha	-0.016	0.11	-10000	0	-0.37	50	50
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.011	0.08	-10000	0	-1.2	1	1
cell motility	0.004	0.075	-10000	0	-0.29	36	36
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.011	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.016	0.018	-10000	0	-0.42	1	1
BCL6	0.008	0.038	-10000	0	-0.46	4	4
HDAC4/CaMK II delta B	0.011	0.019	-10000	0	-0.46	1	1
Hsp90/HDAC6	0.016	0.018	-10000	0	-0.42	1	1
ESR1	-0.033	0.15	-10000	0	-0.52	49	49
HDAC6/HDAC11	0.015	0.025	-10000	0	-0.42	2	2
Ran/GTP/Exportin 1	0.006	0.12	-10000	0	-0.68	15	15
NPC	-0.003	0.056	-10000	0	-0.31	19	19
MEF2C	0	0.076	-10000	0	-0.53	12	12
RAN	0.011	0	-10000	0	-10000	0	0
HDAC4/MEF2C	0.026	0.049	-10000	0	-0.29	10	10
GNG2	0.004	0.063	-10000	0	-0.53	8	8
NCOR2	0.008	0.046	-10000	0	-0.55	4	4
TUBB2A	-0.019	0.12	-10000	0	-0.49	36	36
HDAC11	0.009	0.034	-10000	0	-0.58	2	2
HSP90AA1	0.01	0.024	-10000	0	-0.58	1	1
RANBP2	-0.007	0.1	-10000	0	-0.57	19	19
ANKRA2	0.01	0.024	-10000	0	-0.58	1	1
RFXANK	0.009	0.039	-10000	0	-0.54	3	3
nuclear import	-0.023	0.018	0.32	1	-10000	0	1

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.015	0.035	-10000	0	-0.54	2	2
CRKL	0.014	0.061	-10000	0	-10000	0	0
mol:PIP3	-0.01	0.054	0.52	6	-10000	0	6
AKT1	0.004	0.038	0.36	6	-0.3	1	7
PTK2B	0.009	0.034	-10000	0	-0.58	2	2
RAPGEF1	0.018	0.06	-10000	0	-0.37	1	1
RANBP10	0.011	0	-10000	0	-10000	0	0
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
HGF/MET/SHIP2	-0.009	0.1	-10000	0	-0.32	55	55
MAP3K5	0.004	0.1	-10000	0	-0.4	15	15
HGF/MET/CIN85/CBL/ENDOPHILINS	0	0.093	-10000	0	-0.32	38	38
AP1	-0.012	0.095	-10000	0	-0.34	45	45
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.011	0	-10000	0	-10000	0	0
apoptosis	-0.024	0.16	-10000	0	-0.74	29	29
STAT3 (dimer)	0.011	0.075	-10000	0	-0.41	1	1
GAB1/CRKL/SHP2/PI3K	-0.017	0.066	-10000	0	-0.68	3	3
INPP5D	-0.017	0.12	-10000	0	-0.58	28	28
CBL/CRK	0.019	0.061	-10000	0	-0.44	1	1
PTPN11	0.006	0.054	-10000	0	-0.58	5	5
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.01	0.024	-10000	0	-0.58	1	1
PTEN	0.005	0.059	-10000	0	-0.58	6	6
ELK1	-0.001	0.025	0.23	2	-0.31	2	4
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.013	0.046	-10000	0	-0.36	3	3
PAK1	0.009	0.035	0.34	6	-0.28	1	7
HGF/MET/RANBP10	-0.008	0.1	-10000	0	-0.32	54	54
HRAS	0.004	0.095	-10000	0	-1.1	1	1
DOCK1	0.018	0.062	-10000	0	-0.53	1	1
GAB1	0.008	0.064	-10000	0	-0.28	2	2
CRK	0.013	0.063	-10000	0	-0.47	1	1
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.008	0.13	-10000	0	-0.49	37	37
JUN	0.007	0.052	-10000	0	-0.56	5	5
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.005	0.057	-10000	0	-0.21	38	38
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
cell morphogenesis	0.028	0.091	-10000	0	-0.59	4	4
GRB2/SHC	0.01	0.051	-10000	0	-0.24	2	2
FOS	-0.026	0.14	-10000	0	-0.53	41	41
GLMN	-0.008	0.046	-10000	0	-0.27	18	18
cell motility	-0.001	0.025	0.23	2	-0.31	2	4
HGF/MET/MUC20	-0.016	0.1	-10000	0	-0.33	54	54
cell migration	0.01	0.051	-10000	0	-0.24	2	2
GRB2	0.011	0	-10000	0	-10000	0	0
CBL	0.011	0	-10000	0	-10000	0	0
MET/RANBP10	0.016	0.023	-10000	0	-0.37	2	2
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.006	0.076	-10000	0	-0.26	2	2
MET/MUC20	0.007	0.022	-10000	0	-0.38	2	2
RAP1B	0.023	0.058	-10000	0	-0.34	1	1
RAP1A	0.023	0.059	-10000	0	-0.34	1	1
HGF/MET/RANBP9	-0.009	0.1	-10000	0	-0.33	54	54
RAF1	0.01	0.09	-10000	0	-1	1	1
STAT3	0.011	0.076	-10000	0	-0.41	1	1
cell proliferation	0.015	0.097	-10000	0	-0.34	38	38
RPS6KB1	-0.001	0.043	-10000	0	-0.33	5	5
MAPK3	-0.004	0.031	0.67	1	-0.24	1	2
MAPK1	-0.004	0.031	0.67	1	-0.2	2	3
RANBP9	0.01	0.024	-10000	0	-0.58	1	1
MAPK8	0.019	0.089	-10000	0	-0.36	14	14
SRC	0.012	0.074	-10000	0	-0.53	1	1
PI3K	0.007	0.062	-10000	0	-0.39	5	5
MET/Glomulin	0.003	0.042	-10000	0	-0.22	20	20
SOS1	0.01	0.024	-10000	0	-0.58	1	1
MAP2K1	0.015	0.089	-10000	0	-1.1	1	1
MET	0.01	0.031	-10000	0	-0.52	2	2
MAP4K1	-0.002	0.1	-10000	0	-0.44	13	13
PTK2	0.01	0.024	-10000	0	-0.58	1	1
MAP2K2	0.015	0.086	-10000	0	-0.7	2	2
BAD	0.008	0.042	0.34	6	-0.58	1	7
MAP2K4	0.008	0.094	-10000	0	-0.38	13	13
SHP2/GRB2/SOS1/GAB1	-0.016	0.057	-10000	0	-0.47	3	3
INPPL1	0.01	0.024	-10000	0	-0.58	1	1
PXN	0.011	0	-10000	0	-10000	0	0
SH3KBP1	0.01	0.024	-10000	0	-0.58	1	1
HGS	0.002	0.054	-10000	0	-0.25	3	3
PLCgamma1/PKC	0.008	0.018	-10000	0	-0.43	1	1
HGF	-0.037	0.16	-10000	0	-0.54	52	52
RASA1	0.009	0.034	-10000	0	-0.58	2	2
NCK1	0.009	0.034	-10000	0	-0.58	2	2
PTPRJ	0.01	0.024	-10000	0	-0.58	1	1
NCK/PLCgamma1	0.008	0.062	-10000	0	-0.32	4	4
PDPK1	-0.003	0.042	0.41	6	-10000	0	6
HGF/MET/SHIP	-0.026	0.12	-10000	0	-0.34	81	81

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.011	0	-10000	0	-10000	0	0
NFATC1	0.031	0.061	-10000	0	-0.32	3	3
NFATC2	0.016	0.056	-10000	0	-0.38	4	4
NFATC3	0.018	0.02	-10000	0	-0.41	1	1
YWHAE	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.056	0.14	-10000	0	-0.47	37	37
Exportin 1/Ran/NUP214	0.015	0.051	-10000	0	-0.35	11	11
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.069	0.13	-10000	0	-0.47	40	40
BCL2/BAX	0.002	0.077	-10000	0	-0.4	21	21
CaM/Ca2+/Calcineurin A alpha-beta B1	0.009	0.004	-10000	0	-10000	0	0
CaM/Ca2+	0.009	0.004	-10000	0	-10000	0	0
BAX	0.01	0.024	-10000	0	-0.58	1	1
MAPK14	0.011	0.003	-10000	0	-10000	0	0
BAD	0.01	0.031	-10000	0	-0.52	2	2
CABIN1/MEF2D	-0.048	0.14	-10000	0	-0.45	38	38
Calcineurin A alpha-beta B1/BCL2	-0.008	0.1	-10000	0	-0.55	20	20
FKBP8	0.009	0.034	-10000	0	-0.58	2	2
activation-induced cell death of T cells	0.048	0.13	0.44	38	-10000	0	38
KPNB1	0.011	0	-10000	0	-10000	0	0
KPNA2	0.011	0	-10000	0	-10000	0	0
XPO1	0	0.08	-10000	0	-0.58	11	11
SFN	0.005	0.056	-10000	0	-0.47	8	8
MAP3K8	0.009	0.031	-10000	0	-0.52	2	2
NFAT4/CK1 alpha	0.022	0.046	-10000	0	-0.38	6	6
MEF2D/NFAT1/Cbp/p300	0.026	0.093	-10000	0	-0.42	12	12
CABIN1	-0.057	0.14	-10000	0	-0.48	37	37
CALM1	0.011	0.002	-10000	0	-10000	0	0
RAN	0.011	0	-10000	0	-10000	0	0
MAP3K1	0.005	0.059	-10000	0	-0.58	6	6
CAMK4	-0.012	0.11	-10000	0	-0.55	25	25
mol:Ca2+	0	0.003	-10000	0	-10000	0	0
MAPK3	0.01	0.024	-10000	0	-0.58	1	1
YWHAH	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.007	0.094	-10000	0	-0.38	36	36
YWHAB	0.011	0	-10000	0	-10000	0	0
MAPK8	0.01	0.024	-10000	0	-0.58	1	1
MAPK9	0.011	0	-10000	0	-10000	0	0
YWHAG	0.011	0	-10000	0	-10000	0	0
FKBP1A	0.011	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.041	0.06	-10000	0	-0.35	3	3
PRKCH	0.005	0.059	-10000	0	-0.58	6	6
CABIN1/Cbp/p300	0.014	0.036	-10000	0	-0.42	4	4
CASP3	0.009	0.034	-10000	0	-0.58	2	2
PIM1	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.008	0.002	-10000	0	-10000	0	0
apoptosis	-0.005	0.037	0.23	1	-0.65	1	2
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.032	0.03	-10000	0	-0.38	2	2
PRKCB	-0.041	0.16	-10000	0	-0.54	56	56
PRKCE	0.011	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.023	0.018	-10000	0	-0.37	1	1
BAD/BCL-XL	0.016	0.023	-10000	0	-0.37	2	2
PRKCD	0.011	0	-10000	0	-10000	0	0
NUP214	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.031	-10000	0	-0.52	2	2
PRKCA	0.01	0.031	-10000	0	-0.52	2	2
PRKCG	-0.15	0.24	-10000	0	-0.51	182	182
PRKCQ	-0.045	0.17	-10000	0	-0.58	57	57
FKBP38/BCL2	0.002	0.079	-10000	0	-0.4	22	22
EP300	0.007	0.048	-10000	0	-0.58	4	4
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.011	0	-10000	0	-10000	0	0
NFATc/JNK1	0.034	0.061	-10000	0	-0.36	1	1
CaM/Ca2+/FKBP38	0.014	0.022	-10000	0	-0.36	2	2
FKBP12/FK506	0.008	0	-10000	0	-10000	0	0
CSNK1A1	0.014	0.022	-10000	0	-0.36	2	2
CaM/Ca2+/CAMK IV	0.001	0.071	-10000	0	-0.33	25	25
NFATc/ERK1	0.035	0.059	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.069	0.13	-10000	0	-0.47	39	39
NR4A1	0.017	0.12	-10000	0	-0.42	39	39
GSK3B	0.009	0.034	-10000	0	-0.58	2	2
positive T cell selection	0.018	0.02	-10000	0	-0.41	1	1
NFAT1/CK1 alpha	-0.011	0.044	-10000	0	-0.42	4	4
RCH1/ KPNB1	0.017	0	-10000	0	-10000	0	0
YWHAQ	0.011	0	-10000	0	-10000	0	0
PRKACA	0.011	0.003	-10000	0	-10000	0	0
AKAP5	-0.021	0.13	-10000	0	-0.52	36	36
MEF2D	0.01	0.025	-10000	0	-0.59	1	1
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.008	0.042	-10000	0	-0.58	3	3
NFATc/p38 alpha	0.034	0.059	-10000	0	-10000	0	0
CREBBP	0.011	0.002	-10000	0	-10000	0	0
BCL2	-0.008	0.1	-10000	0	-0.55	20	20

×

Sumoylation by RanBP2 regulates transcriptional repression

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	0.011	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.017	0.093	-9999	-0.5	19	19
MDM2/SUMO1	0.004	0.11	-9999	-0.58	19	19
HDAC4	0.011	0.019	-9999	-0.46	1	1
Ran/GTP/Exportin 1/HDAC1	-0.017	0.093	-9999	-0.5	19	19
SUMO1	-0.008	0.1	-9999	-0.58	19	19
NPC/RanGAP1/SUMO1	-0.005	0.095	-9999	-0.44	24	24
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0	0.12	-9999	-0.73	15	15
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	-0.007	0.1	-9999	-0.57	19	19
SUMO1/HDAC4	0.005	0.1	-9999	-0.55	19	19
SUMO1/HDAC1	0.005	0.1	-9999	-0.55	19	19
RANGAP1	0.01	0.031	-9999	-0.52	2	2
MDM2/SUMO1/SUMO1	0.016	0.072	-9999	-0.35	19	19
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	-0.001	0.095	-9999	-0.43	24	24
Ran/GTP	0.005	0.088	-9999	-0.53	14	14
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.008	0.044	-9999	-0.52	4	4
UBE2I	0.011	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.006	0.12	-9999	-0.68	15	15
NPC	-0.003	0.056	-9999	-0.31	19	19
PIAS2	0.01	0.027	-9999	-0.46	2	2
PIAS1	0.011	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Aurora B 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.017	0.087	-9999	-0.47	15	15
STMN1	0.009	0.07	-9999	-0.43	15	15
Aurora B/RasGAP/Survivin	0.025	0.031	-9999	-0.48	2	2
Chromosomal passenger complex/Cul3 protein complex	-0.012	0.078	-9999	-0.22	51	51
BIRC5	0.012	0.019	-9999	-0.46	1	1
DES	-0.11	0.19	-9999	-0.55	93	93
Aurora C/Aurora B/INCENP	0.013	0.061	-9999	-0.3	21	21
Aurora B/TACC1	0.012	0.047	-9999	-0.34	10	10
Aurora B/PP2A	0.019	0.004	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.013	0.012	-9999	-0.28	1	1
mitotic metaphase/anaphase transition	0	0.001	-9999	-10000	0	0
NDC80	0.009	0.068	-9999	-0.43	14	14
Cul3 protein complex	-0.057	0.14	-9999	-0.3	149	149
KIF2C	0.02	0.023	-9999	-0.5	1	1
PEBP1	0.012	0.001	-9999	-10000	0	0
KIF20A	0.009	0.034	-9999	-0.58	2	2
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.018	0.026	-9999	-0.43	2	2
SEPT1	-0.008	0.1	-9999	-0.53	21	21
SMC2	0.002	0.072	-9999	-0.58	9	9
SMC4	-0.004	0.093	-9999	-0.58	15	15
NSUN2/NPM1/Nucleolin	0.024	0.03	-9999	-10000	0	0
PSMA3	0.011	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.001	-9999	-10000	0	0
H3F3B	0.015	0.002	-9999	-10000	0	0
AURKB	0.015	0.006	-9999	-10000	0	0
AURKC	-0.009	0.1	-9999	-0.55	21	21
CDCA8	0.012	0.001	-9999	-10000	0	0
cytokinesis	0.014	0.038	-9999	-10000	0	0
Aurora B/Septin1	0.005	0.056	-9999	-0.32	1	1
AURKA	0.011	0.001	-9999	-10000	0	0
INCENP	0.012	0.001	-9999	-10000	0	0
KLHL13	-0.12	0.22	-9999	-0.5	148	148
BUB1	0.01	0.024	-9999	-0.58	1	1
hSgo1/Aurora B/Survivin	0.022	0.035	-9999	-0.33	5	5
EVI5	0.005	0.064	-9999	-0.58	7	7
RhoA/GTP	-0.001	0.019	-9999	-0.34	1	1
SGOL1	0.006	0.054	-9999	-0.58	5	5
CENPA	0.023	0.024	-9999	-0.26	4	4
NCAPG	0.008	0.042	-9999	-0.58	3	3
Aurora B/HC8 Proteasome	0.019	0.004	-9999	-10000	0	0
NCAPD2	0.011	0	-9999	-10000	0	0
Aurora B/PP1-gamma	0.019	0.019	-9999	-0.43	1	1
RHOA	0.01	0.024	-9999	-0.58	1	1
NCAPH	0.01	0.024	-9999	-0.58	1	1
NPM1	0.012	0.053	-9999	-0.47	7	7
RASA1	0.009	0.034	-9999	-0.58	2	2
KLHL9	0.01	0.024	-9999	-0.58	1	1
mitotic prometaphase	0.001	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.004	-9999	-10000	0	0
PPP1CC	0.01	0.024	-9999	-0.58	1	1
Centraspindlin	0.027	0.021	-9999	-10000	0	0
RhoA/GDP	0.008	0.018	-9999	-0.43	1	1
NSUN2	0.017	0.003	-9999	-10000	0	0
MYLK	-0.005	0.072	-9999	-0.24	48	48
KIF23	0.012	0.001	-9999	-10000	0	0
VIM	0.014	0.048	-9999	-0.37	9	9
RACGAP1	0.012	0.001	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	0.017	0.003	-9999	-10000	0	0
Chromosomal passenger complex	0.028	0.018	-9999	-0.21	3	3
Chromosomal passenger complex/EVI5	0.021	0.051	-9999	-0.3	7	7
TACC1	0.002	0.073	-9999	-0.56	10	10
PPP2R5D	0.011	0	-9999	-10000	0	0
CUL3	0.009	0.034	-9999	-0.58	2	2
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

BARD1 signaling 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
BARD1/CSTF1	0.012	0.047	-10000	0	-0.42	7	7
ATM	0.002	0.072	-10000	0	-0.58	9	9
UBE2D3	0.011	0	-10000	0	-10000	0	0
PRKDC	0.009	0.039	-10000	0	-0.54	3	3
ATR	0.009	0.034	-10000	0	-0.58	2	2
UBE2L3	0.011	0	-10000	0	-10000	0	0
FANCD2	0.013	0.065	-10000	0	-0.44	10	10
protein ubiquitination	0.02	0.062	-10000	0	-0.33	16	16
XRCC5	0.01	0.024	-10000	0	-0.58	1	1
XRCC6	0.011	0	-10000	0	-10000	0	0
M/R/N Complex	0.008	0.09	-10000	0	-0.46	19	19
MRE11A	0.003	0.068	-10000	0	-0.58	8	8
DNA-PK	0.021	0.035	-10000	0	-0.43	3	3
FA complex/FANCD2/Ubiquitin	0.035	0.058	-10000	0	-0.62	3	3
FANCF	0.005	0.059	-10000	0	-0.58	6	6
BRCA1	0.01	0.024	-10000	0	-0.58	1	1
CCNE1	0.009	0.033	-10000	0	-0.46	3	3
CDK2/Cyclin E1	0.015	0.03	-10000	0	-0.34	4	4
FANCG	0.011	0.019	-10000	0	-0.46	1	1
BRCA1/BACH1/BARD1	0.011	0.05	-10000	0	-0.42	8	8
FANCE	0.011	0	-10000	0	-10000	0	0
FANCC	0.011	0	-10000	0	-10000	0	0
NBN	-0.005	0.096	-10000	0	-0.58	16	16
FANCA	0.011	0	-10000	0	-10000	0	0
DNA repair	0.048	0.066	-10000	0	-0.58	4	4
BRCA1/BARD1/ubiquitin	0.011	0.05	-10000	0	-0.42	8	8
BARD1/DNA-PK	0.023	0.049	-10000	0	-0.35	9	9
FANCL	0.008	0.042	-10000	0	-0.58	3	3
mRNA polyadenylation	-0.012	0.047	0.42	7	-10000	0	7
BRCA1/BARD1/CTIP/M/R/N Complex	0.005	0.15	-10000	0	-0.74	18	18
BRCA1/BACH1/BARD1/TopBP1	0.018	0.046	-10000	0	-0.35	9	9
BRCA1/BARD1/P53	-0.009	0.11	-10000	0	-0.33	63	63
BARD1/CSTF1/BRCA1	0.018	0.043	-10000	0	-0.35	8	8
BRCA1/BACH1	0.01	0.024	-10000	0	-0.58	1	1
BARD1	0.004	0.064	-10000	0	-0.58	7	7
PCNA	0.011	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.018	0.043	-10000	0	-0.35	8	8
BRCA1/BARD1/UbcH7	0.018	0.043	-10000	0	-0.35	8	8
BRCA1/BARD1/RAD51/PCNA	0.025	0.04	-10000	0	-0.32	8	8
BARD1/DNA-PK/P53	-0.003	0.11	-10000	0	-0.31	63	63
BRCA1/BARD1/Ubiquitin	0.011	0.05	-10000	0	-0.42	8	8
BRCA1/BARD1/CTIP	0.009	0.097	-10000	0	-0.41	25	25
FA complex	0.028	0.052	-10000	0	-1	1	1
BARD1/EWS	0.012	0.047	-10000	0	-0.42	7	7
RBBP8	0.001	0.1	-10000	0	-0.53	19	19
TP53	-0.044	0.17	-10000	0	-0.58	56	56
TOPBP1	0.01	0.024	-10000	0	-0.58	1	1
G1/S transition of mitotic cell cycle	0.009	0.11	0.33	63	-10000	0	63
BRCA1/BARD1	0.023	0.063	-10000	0	-0.33	16	16
CSTF1	0.011	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.003	0.047	-10000	0	-0.43	7	7
CDK2	0.01	0.024	-10000	0	-0.58	1	1
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.011	0	-10000	0	-10000	0	0
RAD50	0.01	0.024	-10000	0	-0.58	1	1
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.011	0.05	-10000	0	-0.42	8	8
EWSR1	0.011	0	-10000	0	-10000	0	0

×

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	0.04	0.083	-9999	-0.45	3	3
CRKL	0.02	0.068	-9999	-0.42	4	4
mol:DAG	0.026	0.062	-9999	-0.33	8	8
HRAS	0.036	0.065	-9999	-0.41	4	4
MAPK8	0.019	0.048	-9999	-0.34	5	5
RAP1A	0.02	0.071	-9999	-0.45	5	5
GAB1	0.02	0.068	-9999	-0.42	4	4
MAPK14	0.02	0.046	-9999	-0.32	5	5
EPO	0.001	0.054	-9999	-0.46	8	8
PLCG1	0.026	0.063	-9999	-0.34	8	8
EPOR/TRPC2/IP3 Receptors	0.005	0.064	-9999	-0.5	9	9
RAPGEF1	0.01	0.024	-9999	-0.58	1	1
EPO/EPOR (dimer)/SOCS3	0.006	0.076	-9999	-0.34	22	22
GAB1/SHC/GRB2/SOS1	-0.013	0.052	-9999	-0.45	3	3
EPO/EPOR (dimer)	0.006	0.063	-9999	-0.36	16	16
IRS2	0.016	0.076	-9999	-0.41	5	5
STAT1	0.029	0.081	-9999	-0.45	6	6
STAT5B	0.029	0.067	-9999	-0.36	6	6
cell proliferation	0.024	0.045	-9999	-0.36	2	2
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.025	0.082	-9999	-0.52	8	8
TEC	0.02	0.068	-9999	-0.42	4	4
SOCS3	-0.002	0.082	-9999	-0.5	16	16
STAT1 (dimer)	0.029	0.079	-9999	-0.44	6	6
JAK2	-0.007	0.1	-9999	-0.55	21	21
PIK3R1	0.008	0.042	-9999	-0.58	3	3
EPO/EPOR (dimer)/JAK2	0.026	0.074	-9999	-0.31	19	19
EPO/EPOR	0.006	0.063	-9999	-0.36	16	16
LYN	0.012	0.003	-9999	-10000	0	0
TEC/VAV2	0.013	0.092	-9999	-0.42	7	7
elevation of cytosolic calcium ion concentration	0.005	0.063	-9999	-0.5	9	9
SHC1	0.011	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.02	0.053	-9999	-0.35	6	6
mol:IP3	0.026	0.062	-9999	-0.33	8	8
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.011	0.098	-9999	-0.52	5	5
SH2B3	0.011	0.007	-9999	-10000	0	0
NFKB1	0.019	0.048	-9999	-0.34	5	5
EPO/EPOR (dimer)/JAK2/SOCS3	-0.016	0.061	-9999	-0.29	21	21
PTPN6	0.014	0.071	-9999	-0.3	19	19
TEC/VAV2/GRB2	0.018	0.09	-9999	-0.42	6	6
EPOR	0.005	0.064	-9999	-0.5	9	9
INPP5D	-0.017	0.12	-9999	-0.58	28	28
mol:GDP	-0.013	0.053	-9999	-0.46	3	3
SOS1	0.01	0.024	-9999	-0.58	1	1
PLCG2	-0.011	0.11	-9999	-0.54	24	24
CRKL/CBL/C3G	0.031	0.066	-9999	-0.47	2	2
VAV2	0.006	0.094	-9999	-0.33	20	20
CBL	0.02	0.068	-9999	-0.42	4	4
SHC/Grb2/SOS1	-0.014	0.056	-9999	-0.41	5	5
STAT5A	0.029	0.067	-9999	-0.35	7	7
GRB2	0.011	0	-9999	-10000	0	0
STAT5 (dimer)	0.04	0.082	-9999	-0.46	4	4
LYN/PLCgamma2	0.001	0.081	-9999	-0.39	24	24
PTPN11	0.006	0.054	-9999	-0.58	5	5
BTK	-0.002	0.11	-9999	-0.32	40	40
BCL2	0.025	0.16	-9999	-0.86	16	16

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.006	0.087	0.46	7	-10000	0	7
GNAI2	0.011	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.009	0.048	-10000	0	-0.32	12	12
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.046	0.16	-10000	0	-0.49	68	68
RhoA/GTP	-0.005	0.089	-10000	0	-0.47	7	7
negative regulation of cAMP metabolic process	-0.011	0.096	-10000	0	-0.52	6	6
GNAZ	-0.012	0.11	-10000	0	-0.55	25	25
GNAI3	0.011	0	-10000	0	-10000	0	0
GNA12	0.011	0	-10000	0	-10000	0	0
S1PR5	0	0.076	-10000	0	-0.53	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.012	0.096	-10000	0	-0.53	6	6
RhoA/GDP	0.008	0.018	-10000	0	-0.43	1	1
RHOA	0.01	0.024	-10000	0	-0.58	1	1
GNAI1	-0.003	0.089	-10000	0	-0.56	15	15

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.01	0.11	-10000	0	-0.57	22	22
HRAS	0.008	0.041	-10000	0	-0.49	4	4
EGFR	0.004	0.063	-10000	0	-0.53	8	8
AKT	0.017	0.077	-10000	0	-0.34	19	19
FOXO3	0.011	0	-10000	0	-10000	0	0
AKT1	0.01	0.024	-10000	0	-0.58	1	1
FOXO1	0.009	0.034	-10000	0	-0.58	2	2
AKT3	-0.012	0.11	-10000	0	-0.51	26	26
FOXO4	0.01	0.024	-10000	0	-0.58	1	1
MET	0.01	0.031	-10000	0	-0.52	2	2
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
PIK3CB	0.008	0.046	-10000	0	-0.55	4	4
NRAS	0.001	0.076	-10000	0	-0.58	10	10
PIK3CG	-0.044	0.17	-10000	0	-0.55	58	58
PIK3R3	0.008	0.042	-10000	0	-0.58	3	3
PIK3R2	0.01	0.024	-10000	0	-0.58	1	1
NF1	0.008	0.042	-10000	0	-0.58	3	3
RAS	0.008	0.055	0.21	1	-0.31	8	9
ERBB2	0	0.072	-10000	0	-0.46	14	14
proliferation/survival/translation	-0.019	0.045	0.26	7	-0.15	1	8
PI3K	0.009	0.063	0.18	2	-0.26	18	20
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
KRAS	0.006	0.057	-10000	0	-0.56	6	6
FOXO	0.035	0.026	0.16	2	-10000	0	2
AKT2	0.009	0.036	-10000	0	-0.5	3	3
PTEN	0.005	0.059	-10000	0	-0.58	6	6

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.021	0.036	-10000	0	-0.26	10	10
epithelial cell differentiation	0.023	0.023	-10000	0	-0.3	3	3
CYFIP2	0	0.08	-10000	0	-0.58	11	11
ENAH	0.037	0.067	-10000	0	-0.42	6	6
EGFR	0.004	0.063	-10000	0	-0.53	8	8
EPHA2	0.006	0.055	-10000	0	-0.54	6	6
MYO6	0.029	0.022	-10000	0	-0.28	3	3
CTNNB1	0.011	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.014	0.06	-10000	0	-0.38	13	13
AQP5	-0.036	0.098	-10000	0	-0.47	24	24
CTNND1	0.011	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.028	0.025	-10000	0	-0.28	1	1
regulation of calcium-dependent cell-cell adhesion	-0.003	0.093	-10000	0	-0.28	45	45
EGF	-0.18	0.25	-10000	0	-0.51	216	216
NCKAP1	0.009	0.034	-10000	0	-0.58	2	2
AQP3	-0.021	0.066	-10000	0	-0.47	8	8
cortical microtubule organization	0.023	0.023	-10000	0	-0.3	3	3
GO:0000145	0.026	0.024	-10000	0	-0.26	1	1
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.025	0.023	-10000	0	-0.3	3	3
MLLT4	0.009	0.034	-10000	0	-0.58	2	2
ARF6/GDP	-0.005	0.039	-10000	0	-0.48	2	2
ARF6	0.01	0.024	-10000	0	-0.58	1	1
Ephrin A1/EPHA2/NCK1/GIT1	0.024	0.045	-10000	0	-0.37	6	6
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.036	0.025	-10000	0	-10000	0	0
PVRL2	0.01	0.031	-10000	0	-0.52	2	2
ZYX	0.028	0.025	-10000	0	-10000	0	0
ARF6/GTP	0.027	0.047	-10000	0	-0.39	6	6
CDH1	0.01	0.024	-10000	0	-0.58	1	1
EGFR/EGFR/EGF/EGF	-0.084	0.11	-10000	0	-0.48	1	1
RhoA/GDP	-0.002	0.023	-10000	0	-0.28	4	4
actin cytoskeleton organization	0.032	0.027	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.01	0.024	-10000	0	-0.58	1	1
GIT1	0.01	0.024	-10000	0	-0.58	1	1
IGF1R	0.01	0.024	-10000	0	-0.58	1	1
IGF1	-0.073	0.2	-10000	0	-0.52	94	94
DIAPH1	-0.014	0.092	-10000	0	-0.62	13	13
Wnt receptor signaling pathway	-0.023	0.023	0.3	3	-10000	0	3
RHOA	0.01	0.024	-10000	0	-0.58	1	1
RhoA/GTP	-0.005	0.039	-10000	0	-0.48	2	2
CTNNA1	0.009	0.034	-10000	0	-0.58	2	2
VCL	0.032	0.027	-10000	0	-10000	0	0
EFNA1	0.011	0.019	-10000	0	-0.46	1	1
LPP	0.032	0.026	-10000	0	-10000	0	0
Ephrin A1/EPHA2	-0.004	0.031	-10000	0	-10000	0	0
SEC6/SEC8	-0.003	0.025	-10000	0	-10000	0	0
MGAT3	-0.003	0.094	-10000	0	-0.29	45	45
HGF/MET	-0.023	0.072	-10000	0	-10000	0	0
HGF	-0.037	0.16	-10000	0	-0.54	52	52
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.021	0.036	-10000	0	-0.26	10	10
actin cable formation	0.051	0.057	-10000	0	-0.4	3	3
KIAA1543	0.031	0.034	-10000	0	-10000	0	0
KIFC3	0.024	0.041	-10000	0	-0.28	6	6
NCK1	0.009	0.034	-10000	0	-0.58	2	2
EXOC3	0.011	0	-10000	0	-10000	0	0
ACTN1	0.029	0.022	-10000	0	-10000	0	0
NCK1/GIT1	0.015	0.031	-10000	0	-0.42	3	3
mol:GDP	0.023	0.023	-10000	0	-0.3	3	3
EXOC4	0.011	0	-10000	0	-10000	0	0
STX4	0.029	0.022	-10000	0	-10000	0	0
PIP5K1C	0.028	0.025	-10000	0	-0.28	1	1
LIMA1	0.004	0.064	-10000	0	-0.58	7	7
ABI1	0.01	0.024	-10000	0	-0.58	1	1
ROCK1	0.039	0.059	-10000	0	-0.47	4	4
adherens junction assembly	0.038	0.067	-10000	0	-1.1	1	1
IGF-1R heterotetramer/IGF1	-0.038	0.089	-10000	0	-0.55	1	1
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.014	0.034	-10000	0	-0.4	4	4
MET	0.01	0.031	-10000	0	-0.52	2	2
PLEKHA7	0.028	0.025	-10000	0	-0.28	4	4
mol:GTP	0.023	0.045	-10000	0	-0.37	6	6
establishment of epithelial cell apical/basal polarity	0.045	0.029	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	0.021	0.036	-10000	0	-0.26	10	10
regulation of cell-cell adhesion	0.032	0.027	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.021	0.036	-10000	0	-0.26	10	10

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.028	0.083	-9999	-0.48	5	5
TC10/GTP	-0.022	0.071	-9999	-0.47	2	2
Insulin Receptor/Insulin/IRS1/Shp2	0.014	0.062	-9999	-0.34	17	17
HRAS	0.008	0.041	-9999	-0.49	4	4
APS homodimer	-0.014	0.11	-9999	-0.52	29	29
GRB14	-0.12	0.24	-9999	-0.54	142	142
FOXO3	0.002	0.057	-9999	-0.66	3	3
AKT1	-0.031	0.12	-9999	-0.41	3	3
INSR	0.01	0.034	-9999	-0.58	2	2
Insulin Receptor/Insulin	0.027	0.035	-9999	-0.6	1	1
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.007	0.048	-9999	-0.58	4	4
SORBS1	-0.013	0.11	-9999	-0.51	28	28
CRK	0.011	0.019	-9999	-0.46	1	1
PTPN1	0.024	0.035	-9999	-0.59	1	1
CAV1	0.008	0.067	-9999	-0.33	16	16
CBL/APS/CAP/Crk-II/C3G	0.006	0.088	-9999	-0.44	3	3
Insulin Receptor/Insulin/IRS1/NCK2	0.016	0.054	-9999	-0.34	13	13
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.009	0.05	-9999	-0.3	14	14
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.025	0.048	-9999	-0.46	3	3
RPS6KB1	-0.025	0.12	-9999	-0.47	4	4
PARD6A	0.007	0.045	-9999	-0.48	5	5
CBL	0.011	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0.001	0.008	-9999	-10000	0	0
PIK3R1	0.008	0.042	-9999	-0.58	3	3
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.055	0.093	-9999	-0.46	4	4
HRAS/GTP	-0.018	0.067	-9999	-0.47	3	3
Insulin Receptor	0.01	0.034	-9999	-0.58	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.023	0.049	-9999	-0.32	9	9
PRKCI	-0.019	0.054	-9999	-0.59	4	4
Insulin Receptor/Insulin/GRB14/PDK1	-0.064	0.11	-9999	-0.45	3	3
SHC1	0.011	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0.019	0.027	-9999	-10000	0	0
PI3K	-0.009	0.05	-9999	-0.3	14	14
NCK2	0.01	0.024	-9999	-0.58	1	1
RHOQ	0.011	0	-9999	-10000	0	0
mol:H2O2	0	0.004	-9999	-10000	0	0
HRAS/GDP	0.006	0.03	-9999	-0.35	4	4
AKT2	-0.031	0.12	-9999	-0.41	5	5
PRKCZ	-0.017	0.041	-9999	-0.78	1	1
SH2B2	-0.014	0.11	-9999	-0.52	29	29
SHC/SHIP	0.006	0.082	-9999	-0.3	28	28
F2RL2	-0.034	0.16	-9999	-0.56	47	47
TRIP10	0.01	0.024	-9999	-0.58	1	1
Insulin Receptor/Insulin/Shc	0.015	0.026	-9999	-0.3	3	3
TC10/GTP/CIP4/Exocyst	0.015	0.015	-9999	-0.36	1	1
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.027	0.028	-9999	-0.3	1	1
RAPGEF1	0.01	0.024	-9999	-0.58	1	1
RASA1	0.009	0.034	-9999	-0.58	2	2
NCK1	0.009	0.034	-9999	-0.58	2	2
CBL/APS/CAP/Crk-II	0	0.092	-9999	-0.33	27	27
TC10/GDP	0.008	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.02	0.039	-9999	-0.32	7	7
INPP5D	-0.001	0.086	-9999	-0.32	39	39
SOS1	0.01	0.024	-9999	-0.58	1	1
SGK1	-0.012	0.068	-9999	-0.93	3	3
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.006	0.054	-9999	-0.58	5	5
IRS1	0.002	0.072	-9999	-0.58	9	9
p62DOK/RasGAP	0.02	0.028	-9999	-10000	0	0
INS	0	0.036	-9999	-0.49	3	3
mol:PI-3-4-P2	-0.001	0.085	-9999	-0.32	39	39
GRB2	0.011	0	-9999	-10000	0	0
EIF4EBP1	-0.024	0.12	-9999	-0.45	5	5
PTPRA	0.012	0.003	-9999	-10000	0	0
PIK3CA	0.009	0.034	-9999	-0.58	2	2
TC10/GTP/CIP4	0.015	0.015	-9999	-0.36	1	1
PDPK1	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.021	0.044	-9999	-0.41	1	1
Insulin Receptor/Insulin/IRS1	0.01	0.052	-9999	-0.34	12	12
Insulin Receptor/Insulin/IRS3	0.008	0.036	-9999	-0.38	5	5
Par3/Par6	0	0.091	-9999	-0.31	41	41

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0	0.076	-10000	0	-0.27	42	42
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.001	0.019	-10000	0	-0.32	2	2
GNB1/GNG2	0.011	0.04	-10000	0	-0.32	8	8
GNB1	0.011	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	-0.01	0.069	-10000	0	-0.28	36	36
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	0.005	0.018	0.074	36	-10000	0	36
GNAL	-0.02	0.12	-10000	0	-0.5	36	36
GNG2	0.004	0.063	-10000	0	-0.53	8	8
CRH	-0.001	0.026	-10000	0	-0.46	2	2
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.006	0.015	-10000	0	-0.36	1	1
MAPK11	0.001	0.04	-10000	0	-0.22	17	17

×

p38 MAPK signaling pathway

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
TRAF6/ASK1	0.01	0.027	-10000	0	-0.44	2	2
TRAF2/ASK1	0.014	0.027	-10000	0	-0.36	3	3
ATM	0.002	0.072	-10000	0	-0.58	9	9
MAP2K3	0.013	0.096	-10000	0	-0.58	12	12
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.015	0.092	-10000	0	-0.54	12	12
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.004	0.083	-10000	0	-0.46	19	19
TXN	0.007	0	-10000	0	-10000	0	0
CALM1	0.011	0	-10000	0	-10000	0	0
GADD45A	0.009	0.034	-10000	0	-0.58	2	2
GADD45B	0.008	0.038	-10000	0	-0.46	4	4
MAP3K1	0.005	0.059	-10000	0	-0.58	6	6
MAP3K6	0.004	0.067	-10000	0	-0.56	8	8
MAP3K7	0.011	0	-10000	0	-10000	0	0
MAP3K4	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.01	0.055	-10000	0	-0.41	10	10
TAK1/TAB family	0.003	0.021	0.18	3	-10000	0	3
RAC1/OSM/MEKK3	0.02	0.031	-10000	0	-0.4	3	3
TRAF2	0.01	0.024	-10000	0	-0.58	1	1
RAC1/OSM/MEKK3/MKK3	-0.012	0.068	-10000	0	-0.46	12	12
TRAF6	0.006	0.015	-10000	0	-0.36	1	1
RAC1	0.011	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.054	0.17	-10000	0	-0.49	76	76
CCM2	0.01	0.031	-10000	0	-0.52	2	2
CaM/Ca2+/CAMKIIB	-0.025	0.1	-10000	0	-0.29	76	76
MAPK11	-0.003	0.082	-10000	0	-0.48	17	17
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.016	0.098	-10000	0	-0.26	77	77
OSM/MEKK3	0.014	0.038	-10000	0	-0.51	3	3
TAOK1	0.003	0.078	-10000	0	-0.46	14	14
TAOK2	0.008	0.047	-10000	0	-0.35	10	10
TAOK3	0.009	0.044	-10000	0	-0.35	9	9
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.011	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.009	0.034	-10000	0	-0.58	2	2
MAP3K10	0.007	0.05	-10000	0	-0.53	5	5
MAP3K3	0.009	0.034	-10000	0	-0.58	2	2
TRX/ASK1	0.012	0.021	-10000	0	-0.35	2	2
GADD45/MTK1/MTK1	0.017	0.053	-10000	0	-0.37	3	3

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0	-9999	-10000	0	0
HDAC2	0.011	0.001	-9999	-10000	0	0
GNB1/GNG2	0.002	0.088	-9999	-0.34	36	36
forebrain development	-0.003	0.15	-9999	-0.62	19	19
GNAO1	-0.046	0.16	-9999	-0.49	68	68
SMO/beta Arrestin2	-0.001	0.091	-9999	-0.4	29	29
SMO	-0.015	0.12	-9999	-0.56	29	29
ARRB2	0.012	0.002	-9999	-10000	0	0
GLI3/SPOP	0.014	0.099	-9999	-0.67	5	5
mol:GTP	0	0.001	-9999	-10000	0	0
GSK3B	0.009	0.034	-9999	-0.58	2	2
GNAI2	0.012	0.002	-9999	-10000	0	0
SIN3/HDAC complex	0.026	0.03	-9999	-0.32	4	4
GNAI1	-0.003	0.089	-9999	-0.56	15	15
XPO1	0.003	0.08	-9999	-0.58	11	11
GLI1/Su(fu)	-0.038	0.13	-9999	-0.77	9	9
SAP30	0.009	0.034	-9999	-0.58	2	2
mol:GDP	-0.015	0.12	-9999	-0.55	29	29
MIM/GLI2A	0.002	0.092	-9999	-0.55	16	16
IFT88	0.007	0.048	-9999	-0.58	4	4
GNAI3	0.012	0.002	-9999	-10000	0	0
GLI2	0.023	0.06	-9999	-0.57	2	2
GLI3	0.008	0.1	-9999	-0.72	5	5
CSNK1D	0.011	0	-9999	-10000	0	0
CSNK1E	0.011	0	-9999	-10000	0	0
SAP18	0.01	0.019	-9999	-0.46	1	1
embryonic digit morphogenesis	0.007	0.048	-9999	-0.58	4	4
GNG2	0.004	0.063	-9999	-0.53	8	8
Gi family/GTP	-0.017	0.11	-9999	-0.48	16	16
SIN3B	0.01	0.024	-9999	-0.58	1	1
SIN3A	0.01	0.024	-9999	-0.58	1	1
GLI3/Su(fu)	0.025	0.082	-9999	-0.55	5	5
GLI2/Su(fu)	0.03	0.068	-9999	-0.49	2	2
FOXA2	-0.037	0.18	-9999	-0.95	22	22
neural tube patterning	-0.003	0.15	-9999	-0.62	19	19
SPOP	0.011	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.019	0.043	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
CSNK1G2	0.009	0.034	-9999	-0.58	2	2
CSNK1G3	0.01	0.024	-9999	-0.58	1	1
MTSS1	0.001	0.093	-9999	-0.55	16	16
embryonic limb morphogenesis	-0.003	0.15	-9999	-0.62	19	19
SUFU	0.014	0.048	-9999	-10000	0	0
LGALS3	0.009	0.036	-9999	-0.5	3	3
catabolic process	0.026	0.11	-9999	-0.6	6	6
GLI3A/CBP	0.006	0.066	-9999	-0.35	18	18
KIF3A	0	0.08	-9999	-0.58	11	11
GLI1	-0.004	0.15	-9999	-0.64	19	19
RAB23	0.006	0.055	-9999	-0.54	6	6
CSNK1A1	0.009	0.034	-9999	-0.58	2	2
IFT172	0.011	0	-9999	-10000	0	0
RBBP7	0.01	0.024	-9999	-0.58	1	1
Su(fu)/Galectin3	0.017	0.049	-9999	-0.37	2	2
GNAZ	-0.012	0.11	-9999	-0.55	25	25
RBBP4	0.01	0.024	-9999	-0.58	1	1
CSNK1G1	0.01	0.024	-9999	-0.58	1	1
PIAS1	0.011	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GLI2/SPOP	0.027	0.056	-9999	-0.54	2	2
STK36	0.014	0.003	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.009	0.1	-9999	-0.44	15	15
PTCH1	-0.003	0.17	-9999	-1	10	10
MIM/GLI1	-0.001	0.17	-9999	-0.61	27	27
CREBBP	0.006	0.066	-9999	-0.35	18	18
Su(fu)/SIN3/HDAC complex	0.035	0.027	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.011	0	-9999	-10000	0	0
Rac1/GDP	0.003	0.011	-9999	-10000	0	0
DOCK1	0.01	0.024	-9999	-0.58	1	1
ITGA4	-0.018	0.13	-9999	-0.56	30	30
RAC1	0.011	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.022	0.13	-9999	-0.43	52	52
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.011	0.019	-9999	-0.46	1	1
alpha4/beta1 Integrin	0.005	0.08	-9999	-0.35	26	26
alpha4/beta7 Integrin/Paxillin	-0.003	0.1	-9999	-0.36	38	38
lamellipodium assembly	-0.003	0.051	-9999	-0.5	5	5
PIK3CA	0.009	0.034	-9999	-0.58	2	2
PI3K	0.013	0.04	-9999	-0.42	5	5
ARF6	0.01	0.024	-9999	-0.58	1	1
TLN1	0.01	0.024	-9999	-0.58	1	1
PXN	0.018	0	-9999	-10000	0	0
PIK3R1	0.008	0.042	-9999	-0.58	3	3
ARF6/GTP	-0.014	0.058	-9999	-10000	0	0
cell adhesion	0.017	0.069	-9999	-10000	0	0
CRKL/CBL	0.017	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.011	0.073	-9999	-0.32	26	26
ITGB1	0.011	0	-9999	-10000	0	0
ITGB7	-0.014	0.12	-9999	-0.53	28	28
ARF6/GDP	0.002	0.026	-9999	-0.57	1	1
alpha4/beta1 Integrin/Paxillin/VCAM1	0.002	0.12	-9999	-0.4	38	38
p130Cas/Crk/Dock1	0.02	0.037	-9999	-0.36	5	5
VCAM1	-0.02	0.13	-9999	-0.53	35	35
alpha4/beta1 Integrin/Paxillin/Talin	0.018	0.07	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.018	0.07	-9999	-10000	0	0
BCAR1	0.008	0.044	-9999	-0.52	4	4
mol:GDP	-0.017	0.069	-9999	-10000	0	0
CBL	0.011	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GIT1	0.01	0.024	-9999	-0.58	1	1
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.018	0.07	-9999	-10000	0	0
Rac1/GTP	-0.004	0.058	-9999	-0.56	5	5

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.016	0.079	-9999	-0.47	13	13
VEGFR1 homodimer/NRP1	0.008	0.079	-9999	-0.48	13	13
mol:DAG	0.015	0.089	-9999	-0.64	7	7
VEGFR1 homodimer/NRP1/VEGFR 121	0.014	0.074	-9999	-0.45	12	12
CaM/Ca2+	0.02	0.085	-9999	-0.6	7	7
HIF1A	0.007	0.082	-9999	-0.54	12	12
GAB1	0.011	0	-9999	-10000	0	0
AKT1	0.029	0.094	-9999	-0.62	10	10
PLCG1	0.014	0.09	-9999	-0.65	7	7
NOS3	0.026	0.11	-9999	-0.64	9	9
CBL	0.011	0	-9999	-10000	0	0
mol:NO	0.026	0.1	-9999	-0.61	9	9
FLT1	0.013	0.09	-9999	-0.55	13	13
PGF	-0.002	0.078	-9999	-0.47	16	16
VEGFR1 homodimer/NRP2/VEGFR121	0.008	0.099	-9999	-0.79	4	4
CALM1	0.011	0	-9999	-10000	0	0
PIK3CA	0.009	0.034	-9999	-0.58	2	2
eNOS/Hsp90	0.031	0.1	-9999	-0.59	10	10
endothelial cell proliferation	0.004	0.12	-9999	-0.73	7	7
mol:Ca2+	0.015	0.088	-9999	-0.63	7	7
MAPK3	0.023	0.081	-9999	-0.56	7	7
MAPK1	0.023	0.081	-9999	-0.56	7	7
PIK3R1	0.008	0.042	-9999	-0.58	3	3
PLGF homodimer	-0.002	0.078	-9999	-0.47	16	16
PRKACA	0.011	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.002	0.082	-9999	-0.5	16	16
VEGFA homodimer	0.011	0.019	-9999	-0.46	1	1
VEGFR1 homodimer/VEGFA homodimer	0.016	0.08	-9999	-0.48	12	12
platelet activating factor biosynthetic process	0.027	0.08	-9999	-0.54	7	7
PI3K	0.019	0.098	-9999	-0.67	9	9
PRKCA	0.019	0.085	-9999	-0.59	7	7
PRKCB	-0.008	0.12	-9999	-0.6	10	10
VEGFR1 homodimer/PLGF homodimer	0.009	0.094	-9999	-0.49	15	15
VEGFA	0.011	0.019	-9999	-0.46	1	1
VEGFB	0.011	0	-9999	-10000	0	0
mol:IP3	0.015	0.089	-9999	-0.64	7	7
RASA1	0.021	0.078	-9999	-0.69	5	5
NRP2	-0.014	0.11	-9999	-0.5	29	29
VEGFR1 homodimer	0.013	0.09	-9999	-0.55	13	13
VEGFB homodimer	0.011	0	-9999	-10000	0	0
NCK1	0.009	0.034	-9999	-0.58	2	2
eNOS/Caveolin-1	0.025	0.11	-9999	-0.64	9	9
PTPN11	0.006	0.054	-9999	-0.58	5	5
mol:PI-3-4-5-P3	0.018	0.096	-9999	-0.66	9	9
mol:L-citrulline	0.026	0.1	-9999	-0.61	9	9
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.013	0.12	-9999	-0.67	12	12
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.021	0.081	-9999	-0.68	6	6
CD2AP	-0.017	0.13	-9999	-0.58	29	29
PI3K/GAB1	0.024	0.094	-9999	-0.64	9	9
PDPK1	0.022	0.091	-9999	-0.62	9	9
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.019	0.091	-9999	-0.71	7	7
mol:NADP	0.026	0.1	-9999	-0.61	9	9
HSP90AA1	0.01	0.024	-9999	-0.58	1	1
ubiquitin-dependent protein catabolic process	0.012	0.12	-9999	-0.66	12	12
VEGFR1 homodimer/NRP2	0.001	0.11	-9999	-0.43	23	23

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.054	0.058	-9999	-0.34	5	5
ERC1	0.009	0.033	-9999	-0.46	3	3
RIP2/NOD2	0	0.083	-9999	-0.4	24	24
NFKBIA	0.036	0.014	-9999	-10000	0	0
BIRC2	-0.002	0.087	-9999	-0.58	13	13
IKBKB	0.011	0.019	-9999	-0.46	1	1
RIPK2	0.011	0	-9999	-10000	0	0
IKBKG	0.02	0.071	-9999	-0.46	5	5
IKK complex/A20	0.02	0.088	-9999	-0.44	7	7
NEMO/A20/RIP2	0.011	0	-9999	-10000	0	0
XPO1	0	0.08	-9999	-0.58	11	11
NEMO/ATM	0.021	0.091	-9999	-0.53	11	11
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.009	0.051	-9999	-0.36	11	11
IKK complex/ELKS	-0.015	0.064	-9999	-0.49	6	6
BCL10/MALT1/TRAF6	0.017	0.061	-9999	-0.49	7	7
NOD2	-0.012	0.11	-9999	-0.56	24	24
NFKB1	0.013	0.024	-9999	-0.58	1	1
RELA	0.014	0	-9999	-10000	0	0
MALT1	0.006	0.054	-9999	-0.58	5	5
cIAP1/UbcH5C	0.007	0.064	-9999	-0.42	13	13
ATM	0.002	0.072	-9999	-0.58	9	9
TNF/TNFR1A	-0.004	0.09	-9999	-0.39	30	30
TRAF6	0.01	0.024	-9999	-0.58	1	1
PRKCA	0.01	0.031	-9999	-0.52	2	2
CHUK	0.007	0.048	-9999	-0.58	4	4
UBE2D3	0.011	0	-9999	-10000	0	0
TNF	-0.017	0.12	-9999	-0.54	30	30
NF kappa B1 p50/RelA	0.032	0.015	-9999	-0.34	1	1
BCL10	0.007	0.048	-9999	-0.58	4	4
proteasomal ubiquitin-dependent protein catabolic process	0.036	0.014	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
TNFRSF1A	0.011	0	-9999	-10000	0	0
IKK complex	0.029	0.078	-9999	-0.56	5	5
CYLD	0.01	0.024	-9999	-0.58	1	1
IKK complex/PKC alpha	0.031	0.077	-9999	-0.58	4	4

×

Aurora A signaling

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
Aurora A/GADD45A	0.02	0.025	-9999	-0.35	2	2
BIRC5	0.011	0.019	-9999	-0.46	1	1
NFKBIA	0.023	0.013	-9999	-10000	0	0
CPEB1	-0.052	0.17	-9999	-0.54	67	67
AKT1	0.022	0.02	-9999	-0.35	1	1
NDEL1	0.011	0	-9999	-10000	0	0
Aurora A/BRCA1	0.019	0.023	-9999	-0.49	1	1
NDEL1/TACC3	0.025	0.015	-9999	-10000	0	0
GADD45A	0.009	0.034	-9999	-0.58	2	2
GSK3B	0.009	0.033	-9999	-0.55	2	2
PAK1/Aurora A	0.021	0.013	-9999	-10000	0	0
MDM2	0.008	0.044	-9999	-0.52	4	4
JUB	0.011	0	-9999	-10000	0	0
TPX2	0.017	0.025	-9999	-0.42	2	2
TP53	-0.01	0.11	-9999	-0.33	57	57
DLG7	0.015	0.013	-9999	-0.2	2	2
AURKAIP1	0.01	0.031	-9999	-0.52	2	2
ARHGEF7	0.011	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.026	0.016	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.018	0.023	-9999	-0.49	1	1
AURKA	0.019	0.016	-9999	-0.24	2	2
AURKB	0.011	0.02	-9999	-0.22	4	4
CDC25B	0.023	0.016	-9999	-10000	0	0
G2/M transition checkpoint	0.019	0.012	-9999	-10000	0	0
mRNA polyadenylation	-0.019	0.098	-9999	-0.29	67	67
Aurora A/CPEB	-0.019	0.099	-9999	-0.29	67	67
Aurora A/TACC1/TRAP/chTOG	0.028	0.043	-9999	-0.31	8	8
BRCA1	0.01	0.024	-9999	-0.58	1	1
centrosome duplication	0.021	0.013	-9999	-10000	0	0
regulation of centrosome cycle	0.024	0.015	-9999	-10000	0	0
spindle assembly	0.027	0.043	-9999	-0.31	8	8
TDRD7	0.011	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	0.029	0.033	-9999	-0.4	3	3
CENPA	0.013	0.034	-9999	-0.38	4	4
Aurora A/PP2A	0.021	0.013	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.013	0.049	-9999	-0.57	1	1
negative regulation of DNA binding	-0.01	0.11	-9999	-0.33	57	57
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.016	0.018	-9999	-0.42	1	1
RASA1	0.009	0.034	-9999	-0.58	2	2
Ajuba/Aurora A	0.019	0.012	-9999	-10000	0	0
mitotic prometaphase	0	0.002	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.016	-9999	-0.24	2	2
TACC1	0.002	0.073	-9999	-0.56	10	10
TACC3	0.011	0.019	-9999	-0.46	1	1
Aurora A/Antizyme1	0.026	0.021	-9999	-0.32	1	1
Aurora A/RasGAP	0.02	0.025	-9999	-0.35	2	2
OAZ1	0.011	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.011	0.004	-9999	-10000	0	0
GIT1	0.01	0.024	-9999	-0.58	1	1
GIT1/beta-PIX/PAK1	0.023	0.015	-9999	-0.35	1	1
Importin alpha/Importin beta/TPX2	0.017	0.025	-9999	-0.42	2	2
PPP2R5D	0.011	0	-9999	-10000	0	0
Aurora A/TPX2	0.026	0.02	-9999	-10000	0	0
PAK1	0.011	0	-9999	-10000	0	0
CKAP5	0.011	0	-9999	-10000	0	0

×

Aurora C signaling

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
INCENP	0.011	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.01	0.059	-9999	-0.3	21	21
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.003	0.017	-9999	-10000	0	0
AURKB	0.011	0	-9999	-10000	0	0
AURKC	-0.009	0.1	-9999	-0.55	21	21

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.016	0.069	-10000	0	-0.35	22	22
Ran/GTP/Exportin 1/HDAC1	-0.013	0.075	-10000	0	-0.4	19	19
NF kappa B1 p50/RelA/I kappa B alpha	0.023	0.071	-10000	0	-0.32	22	22
SUMO1	-0.008	0.1	-10000	0	-0.58	19	19
ZFPM1	-0.003	0.084	-10000	0	-0.49	17	17
NPC/RanGAP1/SUMO1/Ubc9	-0.001	0.095	-10000	0	-0.43	24	24
FKBP3	-0.003	0.09	-10000	0	-0.58	14	14
Histones	0.03	0.038	-10000	0	-10000	0	0
YY1/LSF	0.015	0.06	-10000	0	-0.51	3	3
SMG5	0.01	0.024	-10000	0	-0.58	1	1
RAN	0.011	0	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.015	0.058	-10000	0	-10000	0	0
I kappa B alpha/HDAC1	0.018	0.042	-10000	0	-10000	0	0
SAP18	0.011	0.019	-10000	0	-0.46	1	1
RELA	0.018	0.057	-10000	0	-0.24	21	21
HDAC1/Smad7	0.022	0.022	-10000	0	-0.35	2	2
RANGAP1	0.01	0.031	-10000	0	-0.52	2	2
HDAC3/TR2	0.017	0.044	-10000	0	-0.31	1	1
NuRD/MBD3 Complex	0.036	0.031	-10000	0	-0.38	2	2
NF kappa B1 p50/RelA	0.021	0.056	-10000	0	-0.51	1	1
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.018	0.13	-10000	0	-0.56	31	31
GATA1	-0.005	0.074	-10000	0	-0.46	15	15
Mad/Max	0.015	0.026	-10000	0	-0.35	3	3
NuRD/MBD3 Complex/GATA1/Fog1	0.036	0.05	-10000	0	-0.38	5	5
RBBP7	0.01	0.024	-10000	0	-0.58	1	1
NPC	-0.003	0.056	-10000	0	-0.31	19	19
RBBP4	0.01	0.024	-10000	0	-0.58	1	1
MAX	0.011	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.011	0	-10000	0	-10000	0	0
NFKBIA	0.013	0.046	-10000	0	-10000	0	0
KAT2B	-0.006	0.099	-10000	0	-0.58	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.033	0.025	-10000	0	-10000	0	0
SIN3 complex	0.027	0.03	-10000	0	-0.32	4	4
SMURF1	0.011	0	-10000	0	-10000	0	0
CHD3	0.009	0.034	-10000	0	-0.58	2	2
SAP30	0.009	0.034	-10000	0	-0.58	2	2
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.01	0.024	-10000	0	-0.58	1	1
YY1/HDAC3	0.019	0.059	-10000	0	-0.54	1	1
YY1/HDAC2	0.016	0.054	-10000	0	-0.26	20	20
YY1/HDAC1	0.016	0.054	-10000	0	-0.26	20	20
NuRD/MBD2 Complex (MeCP1)	0.035	0.029	-10000	0	-0.36	1	1
PPARG	0.011	0.08	-10000	0	-0.32	29	29
HDAC8/hEST1B	0.023	0.015	-10000	0	-0.35	1	1
UBE2I	0.011	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-10000	0	-10000	0	0
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.016	0.049	-10000	0	-0.31	3	3
MBD3L2	-0.001	0.019	-10000	0	-0.46	1	1
ubiquitin-dependent protein catabolic process	0.022	0.022	-10000	0	-0.35	2	2
CREBBP	0.011	0	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.038	0.032	-10000	0	-0.37	2	2
HDAC1	0.011	0	-10000	0	-10000	0	0
HDAC3	0.013	0.046	-10000	0	-10000	0	0
HDAC2	0.011	0	-10000	0	-10000	0	0
YY1	0.014	0.062	-10000	0	-0.31	20	20
HDAC8	0.011	0	-10000	0	-10000	0	0
SMAD7	0.009	0.034	-10000	0	-0.58	2	2
NCOR2	0.008	0.046	-10000	0	-0.55	4	4
MXD1	0.009	0.036	-10000	0	-0.5	3	3
STAT3	0.019	0.03	-10000	0	-0.34	4	4
NFKB1	0.01	0.024	-10000	0	-0.58	1	1
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	-0.007	0.1	-10000	0	-0.57	19	19
YY1/LSF/HDAC1	0.021	0.055	-10000	0	-0.47	3	3
YY1/SAP30/HDAC1	0.021	0.053	-10000	0	-0.39	3	3
EP300	0.007	0.048	-10000	0	-0.58	4	4
STAT3 (dimer non-phopshorylated)	0.019	0.03	-10000	0	-0.34	4	4
proteasomal ubiquitin-dependent protein catabolic process	0.013	0.046	-10000	0	-10000	0	0
histone deacetylation	0.035	0.029	-10000	0	-0.36	1	1
STAT3 (dimer non-phopshorylated)/HDAC3	0.023	0.044	-10000	0	-10000	0	0
nuclear export	-0.022	0.015	0.35	1	-10000	0	1
PRKACA	0.011	0	-10000	0	-10000	0	0
GATAD2B	0.011	0	-10000	0	-10000	0	0
GATAD2A	0.01	0.024	-10000	0	-0.58	1	1
GATA2/HDAC3	0.001	0.085	-10000	0	-0.33	26	26
GATA1/HDAC1	0.005	0.053	-10000	0	-0.32	15	15
GATA1/HDAC3	0.002	0.057	-10000	0	-0.33	2	2
CHD4	0.011	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	-0.004	0.09	-10000	0	-0.39	30	30
SIN3/HDAC complex/Mad/Max	0.036	0.026	-10000	0	-0.36	1	1
NuRD Complex	0.041	0.038	-10000	0	-0.4	2	2
positive regulation of chromatin silencing	0.028	0.037	-10000	0	-10000	0	0
SIN3B	0.01	0.024	-10000	0	-0.58	1	1
MTA2	0.011	0	-10000	0	-10000	0	0
SIN3A	0.01	0.024	-10000	0	-0.58	1	1
XPO1	0	0.08	-10000	0	-0.58	11	11
SUMO1/HDAC1	0.005	0.1	-10000	0	-0.55	19	19
HDAC complex	0.028	0.02	-10000	0	-0.32	2	2
GATA1/Fog1	-0.005	0.082	-10000	0	-0.35	31	31
FKBP25/HDAC1/HDAC2	0.014	0.057	-10000	0	-0.35	14	14
TNF	-0.017	0.12	-10000	0	-0.54	30	30
negative regulation of cell growth	0.036	0.026	-10000	0	-0.36	1	1
NuRD/MBD2/PRMT5 Complex	0.035	0.029	-10000	0	-0.36	1	1
Ran/GTP/Exportin 1	0.006	0.12	-10000	0	-0.68	15	15
NF kappa B/RelA/I kappa B alpha	0.018	0.071	-10000	0	-0.33	21	21
SIN3/HDAC complex/NCoR1	0.034	0.024	-10000	0	-10000	0	0
TFCP2	0.009	0.034	-10000	0	-0.58	2	2
NR2C1	0.01	0.024	-10000	0	-0.58	1	1
MBD3	0.008	0.046	-10000	0	-0.55	4	4
MBD2	0.006	0.054	-10000	0	-0.58	5	5

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.004	0.094	-9999	-0.41	29	29
AKT1	0.053	0.088	-9999	-0.56	8	8
PTK2B	0.023	0.096	-9999	-0.64	6	6
VEGFR2 homodimer/Frs2	0.021	0.078	-9999	-0.66	6	6
CAV1	-0.002	0.082	-9999	-0.5	16	16
CALM1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.029	0.076	-9999	-0.77	4	4
endothelial cell proliferation	0.046	0.097	-9999	-0.55	6	6
mol:Ca2+	0.034	0.073	-9999	-0.66	4	4
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.034	0.073	-9999	-0.73	4	4
RP11-342D11.1	0.027	0.072	-9999	-0.67	4	4
CDH5	0.005	0.055	-9999	-0.49	7	7
VEGFA homodimer	0.024	0.054	-9999	-0.38	9	9
SHC1	0.011	0	-9999	-10000	0	0
SHC2	-0.041	0.16	-9999	-0.54	57	57
HRAS/GDP	-0.01	0.061	-9999	-0.53	6	6
SH2D2A	0.011	0.019	-9999	-0.46	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.016	0.077	-9999	-0.59	5	5
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.029	0.069	-9999	-0.7	4	4
VEGFR1 homodimer	0.007	0.052	-9999	-0.56	5	5
SHC/GRB2/SOS1	-0.009	0.065	-9999	-0.61	5	5
GRB10	0.033	0.089	-9999	-0.68	7	7
PTPN11	0.006	0.054	-9999	-0.58	5	5
GRB2	0.011	0	-9999	-10000	0	0
PAK1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.035	0.083	-9999	-0.64	7	7
HRAS	0.008	0.041	-9999	-0.49	4	4
VEGF/Rho/ROCK1/Integrin Complex	0.017	0.12	-9999	-0.77	10	10
HIF1A	0.002	0.072	-9999	-0.58	9	9
FRS2	0.009	0.034	-9999	-0.58	2	2
oxygen and reactive oxygen species metabolic process	0.033	0.072	-9999	-0.72	4	4
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.006	0.096	-9999	-0.53	19	19
Nck/Pak	0.015	0.025	-9999	-0.42	2	2
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.026	0.077	-9999	-0.65	5	5
mol:GDP	-0.009	0.063	-9999	-0.59	5	5
mol:NADP	0.042	0.086	-9999	-0.52	5	5
eNOS/Hsp90	0.045	0.083	-9999	-0.48	5	5
PIK3R1	0.008	0.042	-9999	-0.58	3	3
mol:IP3	0.034	0.074	-9999	-0.68	4	4
HIF1A/ARNT	0.01	0.06	-9999	-0.46	9	9
SHB	0.011	0.019	-9999	-0.46	1	1
VEGFA	0.012	0.02	-9999	-0.45	1	1
VEGFC	-0.013	0.11	-9999	-0.54	26	26
FAK1/Vinculin	0.035	0.11	-9999	-0.68	10	10
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.01	0.024	-9999	-0.58	1	1
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.02	0.1	-9999	-0.68	6	6
PTPN6	0.011	0	-9999	-10000	0	0
EPAS1	0.015	0.042	-9999	-0.4	5	5
mol:L-citrulline	0.042	0.086	-9999	-0.52	5	5
ITGAV	0	0.08	-9999	-0.58	11	11
PIK3CA	0.009	0.034	-9999	-0.58	2	2
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.035	0.073	-9999	-0.73	4	4
VEGFR2 homodimer/VEGFA homodimer	0.031	0.079	-9999	-0.73	4	4
VEGFR2/3 heterodimer	0.012	0.1	-9999	-0.52	16	16
VEGFB	0.011	0	-9999	-10000	0	0
MAPK11	0.033	0.085	-9999	-0.61	7	7
VEGFR2 homodimer	0.02	0.079	-9999	-0.61	8	8
FLT1	0.007	0.052	-9999	-0.56	5	5
NEDD4	0.009	0.049	-9999	-0.58	4	4
MAPK3	0.027	0.076	-9999	-0.52	6	6
MAPK1	0.027	0.076	-9999	-0.52	6	6
VEGFA145/NRP2	-0.001	0.082	-9999	-0.35	30	30
VEGFR1/2 heterodimer	0.019	0.079	-9999	-0.53	10	10
KDR	0.02	0.079	-9999	-0.61	8	8
VEGFA165/NRP1/VEGFR2 homodimer	0.023	0.097	-9999	-0.64	7	7
SRC	0.01	0.024	-9999	-0.58	1	1
platelet activating factor biosynthetic process	0.029	0.078	-9999	-0.54	6	6
PI3K	0.045	0.097	-9999	-0.64	8	8
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.029	0.071	-9999	-0.7	4	4
FES	0.029	0.086	-9999	-0.66	5	5
GAB1	-0.011	0.071	-9999	-0.66	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	0.029	0.069	-9999	-0.7	4	4
CTNNB1	0.011	0	-9999	-10000	0	0
SOS1	0.01	0.024	-9999	-0.58	1	1
ARNT	0.01	0.024	-9999	-0.58	1	1
eNOS/Caveolin-1	0.04	0.093	-9999	-0.5	6	6
VEGFR2 homodimer/VEGFA homodimer/Yes	0.026	0.082	-9999	-0.77	4	4
PI3K/GAB1	0.055	0.087	-9999	-0.58	7	7
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.037	0.074	-9999	-0.68	5	5
PRKACA	0.011	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.005	0.12	-9999	-0.67	13	13
HSP90AA1	0.01	0.024	-9999	-0.58	1	1
CDC42	0.032	0.086	-9999	-0.72	5	5
actin cytoskeleton reorganization	0.029	0.068	-9999	-0.69	4	4
PTK2	0.031	0.12	-9999	-0.71	10	10
EDG1	0.027	0.072	-9999	-0.67	4	4
mol:DAG	0.034	0.074	-9999	-0.68	4	4
CaM/Ca2+	0.037	0.068	-9999	-0.62	4	4
MAP2K3	0.038	0.075	-9999	-0.63	5	5
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.035	0.092	-9999	-0.7	7	7
PLCG1	0.034	0.075	-9999	-0.69	4	4
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.035	0.067	-9999	-0.66	4	4
IQGAP1	0.009	0.039	-9999	-0.54	3	3
YES1	0.004	0.064	-9999	-0.58	7	7
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.027	0.08	-9999	-0.77	4	4
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.03	0.068	-9999	-0.7	4	4
cell migration	0.053	0.098	-9999	-0.68	6	6
mol:PI-3-4-5-P3	0.044	0.09	-9999	-0.58	8	8
FYN	0.005	0.06	-9999	-0.55	7	7
VEGFB/NRP1	0.033	0.068	-9999	-0.63	4	4
mol:NO	0.042	0.086	-9999	-0.52	5	5
PXN	0.011	0	-9999	-10000	0	0
HRAS/GTP	-0.01	0.061	-9999	-0.53	6	6
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.034	0.091	-9999	-0.7	7	7
VHL	0.01	0.024	-9999	-0.58	1	1
ITGB3	-0.006	0.098	-9999	-0.54	19	19
NOS3	0.042	0.096	-9999	-0.6	5	5
VEGFR2 homodimer/VEGFA homodimer/Sck	0	0.11	-9999	-0.67	5	5
RAC1	0.011	0	-9999	-10000	0	0
PRKCA	0.038	0.071	-9999	-0.63	4	4
PRKCB	0.012	0.11	-9999	-0.59	7	7
VCL	0.009	0.034	-9999	-0.58	2	2
VEGFA165/NRP1	0.029	0.072	-9999	-0.67	4	4
VEGFR1/2 heterodimer/VEGFA homodimer	0.027	0.077	-9999	-0.63	6	6
VEGFA165/NRP2	-0.001	0.082	-9999	-0.35	30	30
MAPKKK cascade	0.049	0.082	-9999	-0.56	8	8
NRP2	-0.014	0.11	-9999	-0.5	29	29
VEGFC homodimer	-0.013	0.11	-9999	-0.54	26	26
NCK1	0.009	0.034	-9999	-0.58	2	2
ROCK1	0	0.08	-9999	-0.58	11	11
FAK1/Paxillin	0.036	0.11	-9999	-0.64	10	10
MAP3K13	0.034	0.077	-9999	-0.67	5	5
PDPK1	0.048	0.081	-9999	-0.53	7	7

×

ceramide signaling 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
MAP4K4	0.022	0.072	-10000	0	-0.41	4	4
BAG4	0.009	0.034	-10000	0	-0.58	2	2
BAD	0.018	0.036	-10000	0	-0.4	2	2
NFKBIA	0.011	0	-10000	0	-10000	0	0
BIRC3	-0.016	0.12	-10000	0	-0.52	30	30
BAX	0.018	0.034	-10000	0	-0.52	1	1
EnzymeConsortium:3.1.4.12	0.008	0.019	-10000	0	-0.09	3	3
IKBKB	0.026	0.069	-10000	0	-0.48	2	2
MAP2K2	0.027	0.036	-10000	0	-0.3	3	3
MAP2K1	0.026	0.037	-10000	0	-0.27	4	4
SMPD1	0.012	0.024	-10000	0	-0.24	2	2
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.028	0.068	-10000	0	-0.44	1	1
MAP2K4	0.02	0.048	-10000	0	-0.29	10	10
protein ubiquitination	0.027	0.071	-10000	0	-0.44	4	4
EnzymeConsortium:2.7.1.37	0.029	0.041	-10000	0	-0.26	5	5
response to UV	0	0	-10000	0	-0.002	1	1
RAF1	0.023	0.033	-10000	0	-0.24	3	3
CRADD	0.011	0.024	-10000	0	-0.58	1	1
mol:ceramide	0.014	0.029	-10000	0	-0.17	3	3
I-kappa-B-alpha/RELA/p50/ubiquitin	0.015	0	-10000	0	-10000	0	0
MADD	0.012	0	-10000	0	-10000	0	0
MAP3K1	0.016	0.045	-10000	0	-0.32	7	7
TRADD	0.012	0	-10000	0	-10000	0	0
RELA/p50	0.011	0	-10000	0	-10000	0	0
MAPK3	0.028	0.036	-10000	0	-0.25	4	4
MAPK1	0.028	0.036	-10000	0	-0.25	4	4
p50/RELA/I-kappa-B-alpha	0.017	0	-10000	0	-10000	0	0
FADD	0.022	0.069	-10000	0	-0.39	2	2
KSR1	0.018	0.033	-10000	0	-0.26	3	3
MAPK8	0.024	0.047	-10000	0	-0.28	10	10
TRAF2	0.01	0.024	-10000	0	-0.58	1	1
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.025	0.074	-10000	0	-0.51	3	3
TNF R/SODD	0.015	0.025	-10000	0	-0.42	2	2
TNF	-0.016	0.12	-10000	0	-0.54	30	30
CYCS	0.018	0.046	0.13	11	-0.25	8	19
IKBKG	0.026	0.072	-10000	0	-0.51	3	3
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.017	0.072	-10000	0	-0.33	7	7
RELA	0.011	0	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
AIFM1	0.022	0.037	0.13	11	-0.35	2	13
TNF/TNF R/SODD	0.004	0.08	-10000	0	-0.33	32	32
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.02	0.031	-10000	0	-0.58	1	1
NSMAF	0.022	0.068	-10000	0	-0.38	2	2
response to hydrogen peroxide	0	0	-10000	0	-0.002	1	1
BCL2	-0.008	0.1	-10000	0	-0.55	20	20

×

HIF-2-alpha transcription factor network

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
MMP14	-0.009	0.065	-10000	0	-0.86	1	1
oxygen homeostasis	0.005	0.014	-10000	0	-10000	0	0
TCEB2	0.005	0.056	-10000	0	-0.47	8	8
TCEB1	0.011	0.019	-10000	0	-0.46	1	1
VHL/Elongin B/Elongin C/HIF2A	-0.015	0.055	-10000	0	-0.46	4	4
EPO	0.074	0.18	-10000	0	-0.6	7	7
FIH (dimer)	0.017	0.012	-10000	0	-10000	0	0
APEX1	0.017	0.014	-10000	0	-10000	0	0
SERPINE1	0.055	0.23	-10000	0	-0.76	12	12
FLT1	-0.013	0.11	-10000	0	-0.99	6	6
ADORA2A	0.069	0.19	-10000	0	-0.73	7	7
germ cell development	0.065	0.21	-10000	0	-0.72	10	10
SLC11A2	0.075	0.19	-10000	0	-0.71	5	5
BHLHE40	0.075	0.19	-10000	0	-0.75	5	5
HIF1AN	0.017	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.021	0.12	-10000	0	-0.44	6	6
ETS1	0.016	0.063	-10000	0	-0.48	9	9
CITED2	-0.006	0.067	-10000	0	-1.1	2	2
KDR	-0.014	0.11	-10000	0	-0.93	7	7
PGK1	0.075	0.19	-10000	0	-0.71	5	5
SIRT1	0.007	0.054	-10000	0	-0.58	5	5
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.082	0.22	-10000	0	-0.79	7	7
EPAS1	0.049	0.092	-10000	0	-0.37	5	5
SP1	0.016	0.025	-10000	0	-0.58	1	1
ABCG2	0.043	0.24	-10000	0	-0.79	12	12
EFNA1	0.075	0.19	-10000	0	-0.71	5	5
FXN	0.072	0.19	-10000	0	-0.68	6	6
POU5F1	0.064	0.22	-10000	0	-0.75	10	10
neuron apoptosis	-0.08	0.21	0.76	7	-10000	0	7
EP300	0.007	0.048	-10000	0	-0.58	4	4
EGLN3	0.002	0.09	-10000	0	-0.52	17	17
EGLN2	0.015	0.038	-10000	0	-0.49	3	3
EGLN1	0.017	0.012	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.018	0.042	-10000	0	-0.31	9	9
VHL	0.01	0.024	-10000	0	-0.58	1	1
ARNT	0.016	0.029	-10000	0	-0.6	1	1
SLC2A1	0.067	0.2	-10000	0	-0.78	6	6
TWIST1	0.046	0.24	-10000	0	-0.73	16	16
ELK1	0.017	0.025	-10000	0	-0.58	1	1
HIF2A/ARNT/Cbp/p300	0.066	0.12	-10000	0	-0.43	4	4
VEGFA	0.075	0.19	-10000	0	-0.71	5	5
CREBBP	0.011	0	-10000	0	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.015	0.029	-9999	-0.39	3	3
FBXW11	0.011	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.019	0.033	-9999	-0.34	5	5
NF kappa B1 p50/RelA/I kappa B alpha	0.025	0.049	-9999	-10000	0	0
NFKBIA	0.009	0.052	-9999	-0.22	22	22
MAPK14	0.011	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.021	0.019	-9999	-0.35	1	1
ARRB2	0.014	0	-9999	-10000	0	0
REL	0.008	0.042	-9999	-0.58	3	3
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.019	0.031	-9999	-0.32	5	5
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.021	0.019	-9999	-0.31	2	2
PIK3CA	0.009	0.034	-9999	-0.58	2	2
NF kappa B1 p50 dimer	0.015	0.023	-9999	-0.37	2	2
PIK3R1	0.008	0.042	-9999	-0.58	3	3
NFKB1	0.017	0.023	-9999	-0.37	2	2
RELA	0.011	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.014	0.053	-9999	-0.22	22	22
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.028	0.047	-9999	-10000	0	0
SRC	0.01	0.024	-9999	-0.58	1	1
PI3K	0.013	0.04	-9999	-0.42	5	5
NF kappa B1 p50/RelA	0.014	0.053	-9999	-0.22	22	22
IKBKB	0.011	0.019	-9999	-0.46	1	1
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
SYK	0.011	0.019	-9999	-0.46	1	1
I kappa B alpha/PIK3R1	0.013	0.054	-9999	-0.29	3	3
cell death	0.027	0.045	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.019	0.033	-9999	-0.34	5	5
LCK	-0.031	0.14	-9999	-0.51	48	48
BCL3	0.009	0.039	-9999	-0.54	3	3

×

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	0.032	0.026	-9999	-0.46	1	1
KLHL20	-0.019	0.053	-9999	-0.23	28	28
CYFIP2	0	0.08	-9999	-0.58	11	11
Rac1/GDP	0.044	0.04	-9999	-0.49	1	1
ENAH	0.026	0.051	-9999	-0.48	2	2
AP1M1	0.01	0.024	-9999	-0.58	1	1
RAP1B	0.011	0	-9999	-10000	0	0
RAP1A	0.01	0.024	-9999	-0.58	1	1
CTNNB1	0.011	0	-9999	-10000	0	0
CDC42/GTP	-0.004	0.032	-9999	-0.41	2	2
ABI1/Sra1/Nap1	-0.014	0.04	-9999	-0.21	11	11
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.014	0.069	-9999	-0.32	18	18
RAPGEF1	0.04	0.033	-9999	-0.44	2	2
CTNND1	0.011	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.027	0.026	-9999	-0.48	1	1
CRK	0.036	0.028	-9999	-0.43	1	1
E-cadherin/gamma catenin/alpha catenin	0.021	0.031	-9999	-0.35	4	4
alphaE/beta7 Integrin	-0.002	0.086	-9999	-0.39	28	28
IQGAP1	0.009	0.039	-9999	-0.54	3	3
NCKAP1	0.009	0.034	-9999	-0.58	2	2
Rap1/GTP/I-afadin	0.02	0.024	-9999	-0.32	3	3
DLG1	0.031	0.033	-9999	-0.46	1	1
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.003	0.026	-9999	-0.26	5	5
MLLT4	0.009	0.034	-9999	-0.58	2	2
ARF6/GTP/NME1/Tiam1	-0.01	0.094	-9999	-0.28	64	64
PI3K	-0.004	0.034	-9999	-0.34	5	5
ARF6	0.01	0.024	-9999	-0.58	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0.015	0.025	-9999	-0.42	2	2
TIAM1	-0.044	0.16	-9999	-0.52	62	62
E-cadherin(dimer)/Ca2+	0.026	0.023	-9999	-0.3	3	3
AKT1	-0.003	0.023	-9999	-0.23	4	4
PIK3R1	0.008	0.042	-9999	-0.58	3	3
CDH1	0.01	0.024	-9999	-0.58	1	1
RhoA/GDP	0.043	0.041	-9999	-0.49	1	1
actin cytoskeleton organization	0.017	0.051	-9999	-0.17	28	28
CDC42/GDP	0.041	0.047	-9999	-0.42	2	2
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.019	0.023	-9999	-0.26	4	4
ITGB7	-0.014	0.12	-9999	-0.53	28	28
RAC1	0.011	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.028	0.024	-9999	-0.32	3	3
E-cadherin/Ca2+/beta catenin/alpha catenin	0.019	0.023	-9999	-0.3	3	3
mol:GDP	0.04	0.045	-9999	-0.6	1	1
CDC42/GTP/IQGAP1	0.011	0.05	-9999	-0.45	6	6
JUP	0.01	0.024	-9999	-0.58	1	1
p120 catenin/RhoA/GDP	0.035	0.041	-9999	-0.49	1	1
RAC1/GTP/IQGAP1	0.014	0.025	-9999	-0.33	3	3
PIP5K1C/AP1M1	0.016	0.032	-9999	-0.77	1	1
RHOA	0.01	0.024	-9999	-0.58	1	1
CDC42	0.006	0.054	-9999	-0.58	5	5
CTNNA1	0.009	0.034	-9999	-0.58	2	2
positive regulation of S phase of mitotic cell cycle	0.016	0.035	-9999	-0.27	1	1
NME1	0.011	0.019	-9999	-0.46	1	1
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.032	0.028	-9999	-0.46	1	1
regulation of cell-cell adhesion	-0.004	0.028	-9999	-0.35	2	2
WASF2	-0.007	0.021	-9999	-10000	0	0
Rap1/GTP	-0.003	0.026	-9999	-0.44	1	1
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.018	0.069	-9999	-0.44	1	1
CCND1	0.018	0.042	-9999	-0.35	1	1
VAV2	0.008	0.16	-9999	-0.68	28	28
RAP1/GDP	0.036	0.036	-9999	-0.49	1	1
adherens junction assembly	0.031	0.028	-9999	-0.45	1	1
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.01	0.024	-9999	-0.58	1	1
PIP5K1C	0.01	0.024	-9999	-0.58	1	1
regulation of heterotypic cell-cell adhesion	0.023	0.066	-9999	-0.41	1	1
E-cadherin/beta catenin	0	0.022	-9999	-0.35	2	2
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.032	0.028	-9999	-0.46	1	1
PIK3CA	0.009	0.034	-9999	-0.58	2	2
Rac1/GTP	-0.03	0.086	-9999	-0.38	27	27
E-cadherin/beta catenin/alpha catenin	0.022	0.027	-9999	-0.35	3	3
ITGAE	0.011	0.019	-9999	-0.46	1	1
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.027	0.027	-9999	-0.49	1	1

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.027	0.054	-10000	0	-1.1	1	1
regulation of axonogenesis	-0.02	0.045	0.4	4	-10000	0	4
myoblast fusion	-0.016	0.032	0.33	3	-10000	0	3
mol:GTP	0.007	0.022	-10000	0	-0.33	2	2
regulation of calcium-dependent cell-cell adhesion	0.005	0.099	0.33	31	-10000	0	31
ARF1/GTP	-0.002	0.02	-10000	0	-0.31	2	2
mol:GM1	0.007	0.017	-10000	0	-0.26	2	2
mol:Choline	0.02	0.034	-10000	0	-0.43	3	3
lamellipodium assembly	0.006	0.041	-10000	0	-0.46	2	2
MAPK3	0.02	0.028	-10000	0	-0.34	3	3
ARF6/GTP/NME1/Tiam1	-0.004	0.1	-10000	0	-0.34	31	31
ARF1	0.011	0.019	-10000	0	-0.46	1	1
ARF6/GDP	0.016	0.032	-10000	0	-0.33	3	3
ARF1/GDP	0.025	0.033	-10000	0	-0.32	3	3
ARF6	0.01	0.029	-10000	0	-0.67	1	1
RAB11A	0.011	0	-10000	0	-10000	0	0
TIAM1	-0.042	0.16	-10000	0	-0.52	62	62
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.02	0.028	-10000	0	-0.34	3	3
actin filament bundle formation	-0.017	0.036	0.52	2	-10000	0	2
KALRN	0.003	0.042	-10000	0	-0.33	7	7
RAB11FIP3/RAB11A	0.016	0.023	-10000	0	-0.37	2	2
RhoA/GDP	0.017	0.036	-10000	0	-0.52	2	2
NME1	0.012	0.019	-10000	0	-0.45	1	1
Rac1/GDP	0.018	0.027	-10000	0	-0.37	2	2
substrate adhesion-dependent cell spreading	0.007	0.022	-10000	0	-0.33	2	2
cortical actin cytoskeleton organization	0.006	0.041	-10000	0	-0.46	2	2
RAC1	0.011	0	-10000	0	-10000	0	0
liver development	0.007	0.022	-10000	0	-0.33	2	2
ARF6/GTP	0.007	0.022	-10000	0	-0.33	2	2
RhoA/GTP	-0.002	0.029	-10000	0	-0.68	1	1
mol:GDP	0.006	0.037	-10000	0	-0.33	3	3
ARF6/GTP/RAB11FIP3/RAB11A	0.018	0.025	-10000	0	-0.29	3	3
RHOA	0.01	0.024	-10000	0	-0.58	1	1
PLD1	0.015	0.038	-10000	0	-0.49	3	3
RAB11FIP3	0.01	0.031	-10000	0	-0.52	2	2
tube morphogenesis	0.006	0.041	-10000	0	-0.46	2	2
ruffle organization	0.02	0.045	-10000	0	-0.4	4	4
regulation of epithelial cell migration	0.007	0.022	-10000	0	-0.33	2	2
PLD2	0.017	0.017	-10000	0	-0.34	1	1
PIP5K1A	0.02	0.045	-10000	0	-0.41	4	4
mol:Phosphatidic acid	0.02	0.034	-10000	0	-0.43	3	3
Rac1/GTP	0.006	0.041	-10000	0	-0.46	2	2

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.011	0	-10000	0	-10000	0	0
mol:PIP3	-0.004	0.05	0.28	5	-0.29	13	18
FRAP1	0.012	0.017	-10000	0	-10000	0	0
AKT1	0.017	0.048	0.22	5	-0.26	14	19
INSR	0.009	0.034	-10000	0	-0.58	2	2
Insulin Receptor/Insulin	0.005	0.031	-10000	0	-0.32	5	5
mol:GTP	-0.006	0.037	-10000	0	-0.54	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.004	0.027	-10000	0	-0.3	3	3
TSC2	0.009	0.031	-10000	0	-0.52	2	2
RHEB/GDP	-0.005	0.033	-10000	0	-0.49	1	1
TSC1	0.011	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.008	0.048	-10000	0	-0.34	11	11
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.004	0.03	-10000	0	-0.35	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.01	0.024	-10000	0	-0.58	1	1
RPS6KB1	0.017	0.048	-10000	0	-0.4	5	5
MAP3K5	0.007	0.022	-10000	0	-0.38	2	2
PIK3R1	0.008	0.042	-10000	0	-0.58	3	3
apoptosis	0.007	0.022	-10000	0	-0.38	2	2
mol:LY294002	0	0	0.001	1	-0.002	9	10
EIF4B	0.022	0.042	-10000	0	-0.37	4	4
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.022	0.043	-10000	0	-0.34	4	4
eIF4E/eIF4G1/eIF4A1	-0.001	0.016	-10000	0	-0.25	2	2
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.014	0.05	-10000	0	-0.3	14	14
mTOR/RHEB/GTP/Raptor/GBL	0.023	0.024	0.16	5	-0.2	1	6
FKBP1A	0.012	0	-10000	0	-10000	0	0
RHEB/GTP	-0.005	0.033	-10000	0	-0.48	1	1
mol:Amino Acids	0	0	0.001	1	-0.002	9	10
FKBP12/Rapamycin	0.009	0.001	-10000	0	-10000	0	0
PDPK1	-0.004	0.044	0.23	5	-0.26	13	18
EIF4E	0.009	0.039	-10000	0	-0.54	3	3
ASK1/PP5C	0.017	0.039	-10000	0	-0.62	2	2
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.012	0.031	-10000	0	-0.51	2	2
TSC1/TSC2	0.025	0.045	-10000	0	-0.6	1	1
tumor necrosis factor receptor activity	0	0	0.002	9	-0.001	1	10
RPS6	0.007	0.045	-10000	0	-0.48	5	5
PPP5C	0.011	0	-10000	0	-10000	0	0
EIF4G1	0.011	0	-10000	0	-10000	0	0
IRS1	0.001	0.047	-10000	0	-0.38	9	9
INS	-0.002	0.036	-10000	0	-0.5	3	3
PTEN	0.005	0.059	-10000	0	-0.58	6	6
PDK2	-0.005	0.047	0.23	5	-0.27	15	20
EIF4EBP1	0.009	0.044	-10000	0	-1	1	1
PIK3CA	0.009	0.034	-10000	0	-0.58	2	2
PPP2R5D	0.017	0.016	-10000	0	-10000	0	0
peptide biosynthetic process	0.01	0.036	-10000	0	-0.32	4	4
RHEB	0.011	0	-10000	0	-10000	0	0
EIF4A1	0.011	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.003	6	-0.003	1	7
EEF2	0.01	0.036	-10000	0	-0.33	4	4
eIF4E/4E-BP1	0.013	0.047	-10000	0	-0.96	1	1

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.007	0.048	-9999	-0.58	4	4
positive regulation of NF-kappaB transcription factor activity	0.011	0.047	-9999	-0.36	9	9
MAP2K4	0.033	0.036	-9999	-10000	0	0
IKBKB	0.011	0.019	-9999	-0.46	1	1
TNFRSF10B	0.01	0.024	-9999	-0.58	1	1
TNFRSF10A	0.011	0	-9999	-10000	0	0
SMPD1	0.013	0.029	-9999	-0.25	6	6
IKBKG	0.01	0.024	-9999	-0.58	1	1
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.007	0.043	-9999	-0.46	5	5
TRAIL/TRAILR2	0.013	0.04	-9999	-0.42	5	5
TRAIL/TRAILR3	-0.004	0.088	-9999	-0.36	34	34
TRAIL/TRAILR1	0.014	0.036	-9999	-0.42	4	4
TRAIL/TRAILR4	0.011	0.047	-9999	-0.36	9	9
TRAIL/TRAILR1/DAP3/GTP	0.02	0.028	-9999	-0.32	4	4
IKK complex	-0.005	0.038	-9999	-0.4	5	5
RIPK1	0.011	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0.008	0	-9999	-10000	0	0
MAPK3	0.015	0.04	-9999	-0.42	5	5
MAP3K1	0.03	0.03	-9999	-10000	0	0
TRAILR4 (trimer)	0.007	0.043	-9999	-0.46	5	5
TRADD	0.011	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.011	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.028	0.026	-9999	-10000	0	0
CFLAR	0.011	0	-9999	-10000	0	0
MAPK1	0.015	0.04	-9999	-0.42	5	5
TRAIL/TRAILR1/FADD/TRADD/RIP	0.032	0.027	-9999	-10000	0	0
mol:ceramide	0.013	0.028	-9999	-0.25	6	6
FADD	0.011	0	-9999	-10000	0	0
MAPK8	0.037	0.038	-9999	-0.39	1	1
TRAF2	0.01	0.024	-9999	-0.58	1	1
TRAILR3 (trimer)	-0.014	0.11	-9999	-0.49	30	30
CHUK	0.007	0.048	-9999	-0.58	4	4
TRAIL/TRAILR1/FADD	0.021	0.031	-9999	-0.35	4	4
DAP3	0.011	0	-9999	-10000	0	0
CASP10	-0.002	0.036	-9999	-0.34	5	5
JNK cascade	0.011	0.047	-9999	-0.36	9	9
TRAIL (trimer)	0.007	0.048	-9999	-0.58	4	4
TNFRSF10C	-0.014	0.11	-9999	-0.49	30	30
TRAIL/TRAILR1/DAP3/GTP/FADD	0.025	0.027	-9999	-0.3	4	4
TRAIL/TRAILR2/FADD	0.02	0.034	-9999	-0.35	5	5
cell death	0.013	0.028	-9999	-0.25	6	6
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.028	0.028	-9999	-10000	0	0
TRAILR2 (trimer)	0.01	0.024	-9999	-0.58	1	1
CASP8	0	0.035	-9999	-0.8	1	1
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.031	0.03	-9999	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.015	0.073	-9999	-10000	0	0
PLK1	0.054	0.12	-9999	-0.88	3	3
CDKN1B	0.095	0.073	-9999	-0.41	5	5
FOXO3	0.052	0.12	-9999	-0.65	4	4
KAT2B	0.002	0.1	-9999	-0.58	17	17
FOXO1/SIRT1	0.001	0.055	-9999	-0.45	2	2
CAT	0.056	0.12	-9999	-0.73	2	2
CTNNB1	0.011	0	-9999	-10000	0	0
AKT1	0.019	0.027	-9999	-0.57	1	1
FOXO1	0.022	0.049	-9999	-0.28	2	2
MAPK10	0.008	0.083	-9999	-0.29	38	38
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.067	0.066	-9999	-0.58	2	2
response to oxidative stress	0.009	0.013	-9999	-10000	0	0
FOXO3A/SIRT1	-0.001	0.088	-9999	-0.64	4	4
XPO1	0.001	0.08	-9999	-0.58	11	11
EP300	0.008	0.049	-9999	-0.58	4	4
BCL2L11	0.026	0.027	-9999	-10000	0	0
FOXO1/SKP2	0.023	0.054	-9999	-0.51	2	2
mol:GDP	0.009	0.013	-9999	-10000	0	0
RAN	0.013	0.001	-9999	-10000	0	0
GADD45A	0.08	0.089	-9999	-0.88	3	3
YWHAQ	0.011	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.054	0.053	-9999	-0.59	3	3
MST1	-0.025	0.15	-9999	-0.5	51	51
CSNK1D	0.011	0	-9999	-10000	0	0
CSNK1E	0.011	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.043	0.044	-9999	-0.45	3	3
YWHAB	0.011	0	-9999	-10000	0	0
MAPK8	0.032	0.017	-9999	-0.34	1	1
MAPK9	0.032	0.007	-9999	-10000	0	0
YWHAG	0.011	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
YWHAZ	0.008	0.042	-9999	-0.58	3	3
SIRT1	0.009	0.056	-9999	-0.57	5	5
SOD2	0.094	0.086	-9999	-0.63	2	2
RBL2	0.064	0.12	-9999	-1.4	2	2
RAL/GDP	0.026	0.01	-9999	-10000	0	0
CHUK	0.015	0.05	-9999	-0.58	4	4
Ran/GTP	0.012	0.002	-9999	-10000	0	0
CSNK1G2	0.009	0.034	-9999	-0.58	2	2
RAL/GTP	0.032	0.01	-9999	-10000	0	0
CSNK1G1	0.01	0.024	-9999	-0.58	1	1
FASLG	-0.082	0.36	-9999	-1.4	42	42
SKP2	0.008	0.042	-9999	-0.58	3	3
USP7	0.013	0.001	-9999	-10000	0	0
IKBKB	0.018	0.021	-9999	-0.44	1	1
CCNB1	0.056	0.12	-9999	-0.85	1	1
FOXO1-3a-4/beta catenin	0.098	0.089	-9999	-0.44	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.053	-9999	-0.5	2	2
CSNK1A1	0.009	0.034	-9999	-0.58	2	2
SGK1	0.008	0.076	-9999	-0.48	14	14
CSNK1G3	0.01	0.024	-9999	-0.58	1	1
Ran/GTP/Exportin 1	0.014	0.051	-9999	-0.36	11	11
ZFAND5	0.068	0.067	-9999	-0.72	2	2
SFN	0.005	0.056	-9999	-0.47	8	8
CDK2	0.009	0.026	-9999	-0.58	1	1
FOXO3A/14-3-3	0.048	0.051	-9999	-0.42	4	4
CREBBP	0.01	0.009	-9999	-10000	0	0
FBXO32	0.054	0.12	-9999	-0.73	2	2
BCL6	0.065	0.099	-9999	-0.65	2	2
RALB	0.012	0.001	-9999	-10000	0	0
RALA	0.012	0.001	-9999	-10000	0	0
YWHAH	0.011	0	-9999	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.015	0.11	-10000	0	-0.5	30	30
CLTC	0.024	0.032	-10000	0	-0.7	1	1
calcium ion-dependent exocytosis	0.02	0.022	-10000	0	-0.46	1	1
Dynamin 2/GTP	0.019	0.022	-10000	0	-0.29	3	3
EXOC4	0.011	0	-10000	0	-10000	0	0
CD59	0.022	0.031	-10000	0	-0.7	1	1
CPE	-0.038	0.12	-10000	0	-0.32	95	95
CTNNB1	0.011	0	-10000	0	-10000	0	0
membrane fusion	0.02	0.022	-10000	0	-0.45	1	1
CTNND1	0.024	0.021	-10000	0	-0.3	2	2
DNM2	0.01	0.024	-10000	0	-0.58	1	1
mol:PI-4-5-P2	0.024	0.032	-10000	0	-0.5	2	2
TSHR	0	0.062	-10000	0	-0.28	26	26
INS	0.008	0.024	-10000	0	-0.52	1	1
BIN1	0.006	0.054	-10000	0	-0.58	5	5
mol:Choline	0.02	0.022	-10000	0	-0.45	1	1
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.014	0.019	-10000	0	-0.31	2	2
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.01	0.024	-10000	0	-0.58	1	1
mol:Ca2+	0.018	0.022	-10000	0	-0.29	3	3
JUP	0.021	0.032	-10000	0	-0.7	1	1
ASAP2/amphiphysin II	0.017	0.04	-10000	0	-0.32	8	8
ARF6/GTP	0.008	0.018	-10000	0	-0.43	1	1
CDH1	0.021	0.032	-10000	0	-0.7	1	1
clathrin-independent pinocytosis	0.008	0.018	-10000	0	-0.43	1	1
MAPK8IP3	0.005	0.057	-10000	0	-0.51	7	7
positive regulation of endocytosis	0.008	0.018	-10000	0	-0.43	1	1
EXOC2	0.01	0.024	-10000	0	-0.58	1	1
substrate adhesion-dependent cell spreading	0.026	0.065	-10000	0	-0.61	4	4
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.01	0.024	-10000	0	-0.58	1	1
regulation of calcium-dependent cell-cell adhesion	0.002	0.029	0.62	1	-10000	0	1
positive regulation of phagocytosis	0.015	0.015	-10000	0	-0.36	1	1
ARF6/GTP/JIP3	0.011	0.038	-10000	0	-0.31	8	8
ACAP1	0.014	0.032	-10000	0	-0.36	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.009	0.072	-10000	0	-0.7	1	1
clathrin heavy chain/ACAP1	0.027	0.032	-10000	0	-0.46	2	2
JIP4/KLC1	0.021	0.02	-10000	0	-0.32	2	2
EXOC1	0.01	0.024	-10000	0	-0.58	1	1
exocyst	0.026	0.066	-10000	0	-0.62	4	4
RALA/GTP	0.008	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.014	0.022	-10000	0	-0.36	2	2
receptor recycling	0.008	0.018	-10000	0	-0.43	1	1
CTNNA1	0.023	0.028	-10000	0	-0.3	4	4
NME1	0.014	0.019	-10000	0	-0.31	2	2
clathrin coat assembly	0.024	0.031	-10000	0	-0.69	1	1
IL2RA	0.001	0.07	-10000	0	-0.5	2	2
VAMP3	0.015	0.015	-10000	0	-0.36	1	1
GLUT4/clathrin heavy chain/ACAP1	-0.012	0.053	-10000	0	-0.29	12	12
EXOC6	0.008	0.042	-10000	0	-0.58	3	3
PLD1	0.016	0.029	-10000	0	-0.37	3	3
PLD2	0.018	0.008	-10000	0	-10000	0	0
EXOC5	-0.006	0.099	-10000	0	-0.58	17	17
PIP5K1C	0.024	0.032	-10000	0	-0.51	2	2
SDC1	0.021	0.032	-10000	0	-0.7	1	1
ARF6/GDP	0.014	0.019	-10000	0	-0.31	2	2
EXOC7	0.011	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.002	0.03	-10000	0	-0.64	1	1
mol:Phosphatidic acid	0.02	0.022	-10000	0	-0.45	1	1
endocytosis	-0.017	0.039	0.32	8	-10000	0	8
SCAMP2	0.011	0	-10000	0	-10000	0	0
ADRB2	0.008	0.08	-10000	0	-0.28	32	32
EXOC3	0.011	0	-10000	0	-10000	0	0
ASAP2	0.009	0.034	-10000	0	-0.58	2	2
Dynamin 2/GDP	0.02	0.022	-10000	0	-0.29	3	3
KLC1	0.011	0	-10000	0	-10000	0	0
AVPR2	0.003	0.083	-10000	0	-0.29	25	25
RALA	0.011	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.003	0.031	-10000	0	-0.59	1	1

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	-0.007	0.025	0.26	5	-10000	0	5
BUB1B	0.018	0.029	-10000	0	-0.32	4	4
PLK1	0.015	0.006	-10000	0	-10000	0	0
PLK1S1	0.011	0.019	-10000	0	-0.27	2	2
KIF2A	0.02	0.015	-10000	0	-0.32	1	1
regulation of mitotic centrosome separation	0.015	0.006	-10000	0	-10000	0	0
GOLGA2	0.009	0.034	-10000	0	-0.58	2	2
Hec1/SPC24	0.011	0.068	-10000	0	-0.29	29	29
WEE1	0.017	0.044	-10000	0	-0.51	4	4
cytokinesis	0.022	0.049	-10000	0	-0.34	7	7
PP2A-alpha B56	0.029	0.036	-10000	0	-0.78	1	1
AURKA	0.014	0.004	-10000	0	-10000	0	0
PICH/PLK1	0.021	0.058	-10000	0	-0.3	16	16
CENPE	0.01	0.059	-10000	0	-0.32	18	18
RhoA/GTP	0.008	0.018	-10000	0	-0.43	1	1
positive regulation of microtubule depolymerization	0.02	0.015	-10000	0	-0.31	1	1
PPP2CA	0.011	0	-10000	0	-10000	0	0
FZR1	0.01	0.024	-10000	0	-0.58	1	1
TPX2	0.012	0.016	-10000	0	-0.26	2	2
PAK1	0.011	0	-10000	0	-10000	0	0
SPC24	-0.003	0.089	-10000	0	-0.56	15	15
FBXW11	0.011	0	-10000	0	-10000	0	0
CLSPN	0.013	0.013	-10000	0	-0.3	1	1
GORASP1	0.011	0	-10000	0	-10000	0	0
metaphase	0	0.001	-10000	0	-0.016	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.008	0.003	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0.001	0.011	1	-10000	0	1
STAG2	0.007	0.048	-10000	0	-0.58	4	4
GRASP65/GM130/RAB1/GTP	-0.001	0.018	-10000	0	-0.28	1	1
spindle elongation	0.015	0.006	-10000	0	-10000	0	0
ODF2	0.011	0.001	-10000	0	-10000	0	0
BUB1	-0.001	0.035	-10000	0	-0.86	1	1
TPT1	0.013	0.005	-10000	0	-10000	0	0
CDC25C	0.015	0.004	-10000	0	-10000	0	0
CDC25B	0.01	0.027	-10000	0	-0.45	2	2
SGOL1	0.007	0.025	-10000	0	-0.26	5	5
RHOA	0.01	0.024	-10000	0	-0.58	1	1
CCNB1/CDK1	-0.003	0.025	-10000	0	-0.28	4	4
CDC14B	0.007	0.031	-10000	0	-0.43	3	3
CDC20	0.011	0	-10000	0	-10000	0	0
PLK1/PBIP1	0.01	0.046	-10000	0	-0.3	13	13
mitosis	0	0	-10000	0	-10000	0	0
FBXO5	0.016	0.028	-10000	0	-0.31	4	4
CDC2	0.001	0.001	-10000	0	-10000	0	0
NDC80	-0.003	0.09	-10000	0	-0.58	14	14
metaphase plate congression	0.014	0.006	-10000	0	-10000	0	0
ERCC6L	0.019	0.061	-10000	0	-0.31	17	17
NLP/gamma Tubulin	0.012	0.004	-10000	0	-10000	0	0
microtubule cytoskeleton organization	0.013	0.005	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0	-10000	0	-10000	0	0
PPP1R12A	0.007	0.049	-10000	0	-0.58	4	4
interphase	0	0	-10000	0	-10000	0	0
PLK1/PRC1-2	0.026	0.02	-10000	0	-0.3	2	2
GRASP65/GM130/RAB1/GTP/PLK1	0.028	0.023	-10000	0	-0.29	3	3
RAB1A	0.01	0.024	-10000	0	-0.58	1	1
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.017	0.005	-10000	0	-10000	0	0
mitotic prometaphase	0	0.001	0.012	1	-10000	0	1
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.025	-10000	0	-0.4	1	1
microtubule-based process	0.019	0.021	-10000	0	-0.32	2	2
Golgi organization	0.015	0.006	-10000	0	-10000	0	0
Cohesin/SA2	0.015	0.027	-10000	0	-0.31	4	4
PPP1CB/MYPT1	0.012	0.052	-10000	0	-0.48	6	6
KIF20A	0.009	0.034	-10000	0	-0.58	2	2
APC/C/CDC20	0.02	0.006	-10000	0	-10000	0	0
PPP2R1A	0.01	0.024	-10000	0	-0.58	1	1
chromosome segregation	0.01	0.046	-10000	0	-0.29	13	13
PRC1	0.011	0	-10000	0	-10000	0	0
ECT2	0.013	0.051	-10000	0	-0.33	13	13
C13orf34	0.017	0.005	-10000	0	-10000	0	0
NUDC	0.014	0.006	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.018	0.029	-10000	0	-0.32	4	4
spindle assembly	0.015	0.005	-10000	0	-10000	0	0
spindle stabilization	0.011	0.019	-10000	0	-0.27	2	2
APC/C/HCDH1	0.013	0.031	-10000	0	-0.36	4	4
MKLP2/PLK1	0.019	0.021	-10000	0	-0.32	2	2
CCNB1	0.012	0.001	-10000	0	-10000	0	0
PPP1CB	0.008	0.042	-10000	0	-0.59	3	3
BTRC	0.01	0.024	-10000	0	-0.58	1	1
ROCK2	0.012	0.07	-10000	0	-0.48	11	11
TUBG1	0.013	0.003	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.002	0.025	-10000	0	-0.27	4	4
MLF1IP	0	0.065	-10000	0	-0.44	13	13
INCENP	0.011	0.001	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.018	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.025	0.03	-10000	0	-0.32	4	4
CDKN1B	0.024	0.048	-10000	0	-0.52	4	4
CDKN1A	0.022	0.05	-10000	0	-0.41	6	6
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.009	0.039	-10000	0	-0.54	3	3
FOXO3	0.024	0.044	-10000	0	-0.54	3	3
AKT1	-0.005	0.043	-10000	0	-0.48	4	4
BAD	0.01	0.031	-10000	0	-0.52	2	2
AKT3	0.002	0.059	-10000	0	-0.26	26	26
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.024	0.046	-10000	0	-0.47	4	4
AKT1/ASK1	0.023	0.053	-10000	0	-0.58	4	4
BAD/YWHAZ	0.02	0.033	-10000	0	-0.35	4	4
RICTOR	-0.009	0.11	-10000	0	-0.58	20	20
RAF1	0.011	0	-10000	0	-10000	0	0
JNK cascade	-0.022	0.051	0.55	4	-10000	0	4
TSC1	0.024	0.044	-10000	0	-0.54	3	3
YWHAZ	0.008	0.042	-10000	0	-0.58	3	3
AKT1/RAF1	0.025	0.044	-10000	0	-0.54	3	3
EP300	0.007	0.048	-10000	0	-0.58	4	4
mol:GDP	0.019	0.045	-10000	0	-0.47	4	4
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.023	0.053	-10000	0	-0.54	4	4
YWHAQ	0.011	0	-10000	0	-10000	0	0
TBC1D4	0.015	0.04	-10000	0	-0.34	7	7
MAP3K5	0.009	0.034	-10000	0	-0.58	2	2
MAPKAP1	0.011	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.032	0.03	0.32	3	-10000	0	3
YWHAH	0.011	0	-10000	0	-10000	0	0
AKT1S1	0.024	0.052	-10000	0	-0.63	3	3
CASP9	0.024	0.046	-10000	0	-0.47	4	4
YWHAB	0.011	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.028	0.057	-10000	0	-0.63	4	4
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.022	0.022	-10000	0	-0.35	2	2
YWHAE	0.011	0	-10000	0	-10000	0	0
SRC	0.01	0.024	-10000	0	-0.58	1	1
AKT2/p21CIP1	0.026	0.051	-10000	0	-0.38	7	7
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.013	0.014	-10000	0	-10000	0	0
CHUK	0.022	0.058	-10000	0	-0.5	6	6
BAD/BCL-XL	0.035	0.049	-10000	0	-0.58	3	3
mTORC2	0.003	0.062	-10000	0	-0.33	20	20
AKT2	0.013	0.019	-10000	0	-0.24	3	3
FOXO1-3a-4/14-3-3 family	0.042	0.046	-10000	0	-0.45	4	4
PDPK1	0.011	0	-10000	0	-10000	0	0
MDM2	0.022	0.052	-10000	0	-0.49	5	5
MAPKKK cascade	-0.025	0.043	0.52	3	-10000	0	3
MDM2/Cbp/p300	0.032	0.057	-10000	0	-0.49	5	5
TSC1/TSC2	0.028	0.051	-10000	0	-0.6	3	3
proteasomal ubiquitin-dependent protein catabolic process	0.03	0.054	-10000	0	-0.47	5	5
glucose import	0.005	0.071	-10000	0	-0.31	18	18
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.021	0.031	-10000	0	-0.34	3	3
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.005	0.072	-10000	0	-0.31	18	18
GSK3A	0.024	0.044	-10000	0	-0.54	3	3
FOXO1	0.023	0.047	-10000	0	-0.43	5	5
GSK3B	0.023	0.054	-10000	0	-0.59	4	4
SFN	0.005	0.056	-10000	0	-0.47	8	8
G1/S transition of mitotic cell cycle	0.028	0.053	-10000	0	-0.57	4	4
p27Kip1/14-3-3 family	0.036	0.029	-10000	0	-0.39	1	1
PRKACA	0.011	0	-10000	0	-10000	0	0
KPNA1	0.009	0.034	-10000	0	-0.58	2	2
HSP90AA1	0.01	0.024	-10000	0	-0.58	1	1
YWHAG	0.011	0	-10000	0	-10000	0	0
RHEB	0.011	0	-10000	0	-10000	0	0
CREBBP	0.011	0	-10000	0	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.004	0.064	-10000	0	-0.58	7	7
SMAD2	0.013	0.023	0.24	1	-0.25	2	3
SMAD3	0.03	0.031	-10000	0	-0.25	1	1
SMAD3/SMAD4	0.034	0.03	-10000	0	-10000	0	0
SMAD4/Ubc9/PIASy	0.018	0.043	-10000	0	-0.35	8	8
SMAD2/SMAD2/SMAD4	0.029	0.035	-10000	0	-0.26	7	7
PPM1A	0.011	0	-10000	0	-10000	0	0
CALM1	0.011	0	-10000	0	-10000	0	0
SMAD2/SMAD4	0.014	0.041	0.19	1	-0.29	9	10
MAP3K1	0.005	0.059	-10000	0	-0.58	6	6
TRAP-1/SMAD4	0.01	0.053	-10000	0	-0.42	9	9
MAPK3	0.01	0.024	-10000	0	-0.58	1	1
MAPK1	0.01	0.024	-10000	0	-0.58	1	1
NUP214	0.011	0	-10000	0	-10000	0	0
CTDSP1	0.01	0.024	-10000	0	-0.58	1	1
CTDSP2	0.011	0	-10000	0	-10000	0	0
CTDSPL	0.011	0	-10000	0	-10000	0	0
KPNB1	0.011	0	-10000	0	-10000	0	0
TGFBRAP1	0.009	0.034	-10000	0	-0.58	2	2
UBE2I	0.011	0	-10000	0	-10000	0	0
NUP153	0.011	0	-10000	0	-10000	0	0
KPNA2	0.011	0	-10000	0	-10000	0	0
PIAS4	0.01	0.024	-10000	0	-0.58	1	1

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.036	0.057	-10000	0	-1.1	1	1
CLOCK	0.012	0.031	-10000	0	-0.51	2	2
TIMELESS/CRY2	0.033	0.054	-10000	0	-1.2	1	1
DEC1/BMAL1	0.006	0.049	-10000	0	-0.33	12	12
ATR	0.009	0.034	-10000	0	-0.58	2	2
NR1D1	0.031	0.06	-10000	0	-1.3	1	1
ARNTL	0.012	0.034	-10000	0	-0.58	2	2
TIMELESS	0.031	0.058	-10000	0	-1.3	1	1
NPAS2	0.012	0.031	-10000	0	-0.51	2	2
CRY2	0.011	0	-10000	0	-10000	0	0
mol:CO	-0.011	0.009	0.12	3	-10000	0	3
CHEK1	0.01	0.024	-10000	0	-0.58	1	1
mol:HEME	0.011	0.009	-10000	0	-0.12	3	3
PER1	0.004	0.063	-10000	0	-0.5	9	9
BMAL/CLOCK/NPAS2	0.033	0.037	-10000	0	-0.35	4	4
BMAL1/CLOCK	0.034	0.067	-10000	0	-0.88	2	2
S phase of mitotic cell cycle	0.036	0.057	-10000	0	-1.1	1	1
TIMELESS/CHEK1/ATR	0.036	0.058	-10000	0	-1.2	1	1
mol:NADPH	0.011	0.009	-10000	0	-0.12	3	3
PER1/TIMELESS	0.029	0.067	-10000	0	-0.93	2	2
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	-0.004	0.059	-10000	0	-0.46	10	10

×

Insulin-mediated glucose transport

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.01	0.058	-10000	0	-0.37	5	5
CaM/Ca2+	0.008	0	-10000	0	-10000	0	0
AKT1	0.01	0.024	-10000	0	-0.58	1	1
AKT2	0.009	0.036	-10000	0	-0.5	3	3
STXBP4	0.005	0.059	-10000	0	-0.58	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.029	0.056	0.2	6	-0.36	4	10
YWHAZ	0.008	0.042	-10000	0	-0.58	3	3
CALM1	0.011	0	-10000	0	-10000	0	0
YWHAQ	0.011	0	-10000	0	-10000	0	0
TBC1D4	0.013	0.047	-10000	0	-0.42	7	7
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.011	0	-10000	0	-10000	0	0
YWHAB	0.011	0	-10000	0	-10000	0	0
SNARE/Synip	0.019	0.038	-10000	0	-0.35	6	6
YWHAG	0.011	0	-10000	0	-10000	0	0
ASIP	0	0.054	-10000	0	-0.46	8	8
PRKCI	0.008	0.042	-10000	0	-0.58	3	3
AS160/CaM/Ca2+	0.008	0	-10000	0	-10000	0	0
RHOQ	0.011	0	-10000	0	-10000	0	0
GYS1	0.022	0.043	-10000	0	-0.47	4	4
PRKCZ	0.01	0.031	-10000	0	-0.52	2	2
TRIP10	0.01	0.024	-10000	0	-0.58	1	1
TC10/GTP/CIP4/Exocyst	0.015	0.015	-10000	0	-0.36	1	1
AS160/14-3-3	0.033	0.034	-10000	0	-0.34	2	2
VAMP2	0.011	0	-10000	0	-10000	0	0
SLC2A4	0.029	0.06	0.2	6	-0.4	4	10
STX4	0.011	0	-10000	0	-10000	0	0
GSK3B	0.018	0.045	-10000	0	-0.58	3	3
SFN	0.005	0.056	-10000	0	-0.47	8	8
LNPEP	0.003	0.068	-10000	0	-0.58	8	8
YWHAE	0.011	0	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.035	0.051	-10000	0	-0.41	6	6
adherens junction organization	0.033	0.033	-10000	0	-0.46	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.037	0.051	-10000	0	-0.48	3	3
FMN1	0.028	0.048	-10000	0	-0.41	2	2
mol:IP3	0.03	0.038	-10000	0	-0.38	2	2
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.028	0.03	-10000	0	-0.37	2	2
CTNNB1	0.011	0.001	-10000	0	-10000	0	0
AKT1	0.035	0.043	-10000	0	-0.69	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.032	0.039	-10000	0	-0.56	2	2
CTNND1	0.012	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.031	0.036	-10000	0	-0.39	3	3
VASP	0.033	0.029	-10000	0	-0.46	1	1
ZYX	0.032	0.038	-10000	0	-0.74	1	1
JUB	0.033	0.029	-10000	0	-0.46	1	1
EGFR(dimer)	0.029	0.045	-10000	0	-0.4	3	3
E-cadherin/beta catenin-gamma catenin	0.021	0.021	-10000	0	-0.34	2	2
mol:PI-3-4-5-P3	0.03	0.038	-10000	0	-0.3	6	6
PIK3CA	0.01	0.034	-10000	0	-0.58	2	2
PI3K	0.031	0.038	-10000	0	-0.31	6	6
FYN	0.031	0.054	-10000	0	-0.33	7	7
mol:Ca2+	0.029	0.037	-10000	0	-0.37	2	2
JUP	0.01	0.024	-10000	0	-0.59	1	1
PIK3R1	0.009	0.042	-10000	0	-0.58	3	3
mol:DAG	0.03	0.038	-10000	0	-0.38	2	2
CDH1	0.01	0.024	-10000	0	-0.58	1	1
RhoA/GDP	0.037	0.054	-10000	0	-0.49	4	4
establishment of polarity of embryonic epithelium	0.032	0.028	-10000	0	-0.45	1	1
SRC	0.01	0.024	-10000	0	-0.58	1	1
RAC1	0.011	0	-10000	0	-10000	0	0
RHOA	0.01	0.024	-10000	0	-0.58	1	1
EGFR	0.004	0.063	-10000	0	-0.53	8	8
CASR	0.028	0.044	-10000	0	-0.45	1	1
RhoA/GTP	0.032	0.039	-10000	0	-0.47	2	2
AKT2	0.034	0.047	-10000	0	-0.58	2	2
actin cable formation	0.033	0.047	-10000	0	-0.4	2	2
apoptosis	-0.032	0.047	0.37	6	-10000	0	6
CTNNA1	0.01	0.035	-10000	0	-0.58	2	2
mol:GDP	0.032	0.054	-10000	0	-0.52	3	3
PIP5K1A	0.032	0.037	-10000	0	-0.4	3	3
PLCG1	0.03	0.038	-10000	0	-0.5	1	1
Rac1/GTP	-0.005	0.036	-10000	0	-0.37	3	3
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

Arf1 pathway

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
coatomer protein complex	-0.002	0.029	-9999	-0.63	1	1
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.015	0.021	-9999	-0.23	3	3
AP2	0.015	0.03	-9999	-0.34	4	4
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0.016	0.002	-9999	-10000	0	0
CLTB	0.01	0.031	-9999	-0.52	2	2
coatomer protein complex/ARF1/GTP/ER cargo protein	0.02	0.014	-9999	-0.26	1	1
CD4	-0.014	0.12	-9999	-0.55	27	27
CLTA	0.011	0	-9999	-10000	0	0
mol:GTP	0.001	0.001	-9999	-10000	0	0
ARFGAP1	0.007	0.026	-9999	-0.36	3	3
mol:PI-4-5-P2	-0.001	0.019	-9999	-0.32	2	2
ARF1/GTP	-0.001	0.012	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.02	0.025	-9999	-0.48	1	1
mol:Choline	-0.001	0.019	-9999	-0.32	2	2
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.011	0.019	-9999	-0.45	1	1
DDEF1	-0.001	0.019	-9999	-0.33	2	2
ARF1/GDP	0.005	0.021	-9999	-0.26	3	3
AP2M1	0.011	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.013	0.01	-9999	-0.22	1	1
Rac/GTP	0.009	0.001	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.02	0.021	-9999	-0.25	3	3
ARFIP2	0.01	0.003	-9999	-10000	0	0
COPA	0.011	0	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.02	0.01	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0.008	0.011	-9999	-0.26	1	1
GGA3	0.011	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0.015	0.011	-9999	-0.2	1	1
AP2A1	0.008	0.041	-9999	-0.49	4	4
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.02	0.028	-9999	-0.61	1	1
ARF1/GDP/Membrin	0.015	0.011	-9999	-0.19	1	1
Arfaptin 2/Rac/GDP	0.015	0.002	-9999	-10000	0	0
CYTH2	0.012	0.001	-9999	-10000	0	0
ARF1/GTP/GGA3	0.016	0.011	-9999	-0.25	1	1
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.008	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	0.018	0.05	-9999	-0.4	1	1
PLD2	-0.001	0.019	-9999	-0.32	2	2
ARF-GAP1/v-SNARE	0.007	0.026	-9999	-0.36	3	3
PIP5K1A	-0.001	0.019	-9999	-0.33	2	2
ARF1/GTP/Membrin/GBF1/p115	-0.002	0.019	-9999	-0.28	2	2
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.001	0.019	-9999	-0.32	2	2
KDEL Receptor/Ligand/ARF-GAP1	0.007	0.026	-9999	-0.36	3	3
GOSR2	-0.001	0.008	-9999	-10000	0	0
USO1	-0.005	0.049	-9999	-0.48	6	6
GBF1	-0.001	0.019	-9999	-0.42	1	1
ARF1/GTP/Arfaptin 2	0.016	0.011	-9999	-0.24	1	1
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.005	0.078	-9999	-0.33	31	31

×

Alternative NF-kappaB 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
IKK alpha homodimer	0.013	0.04	-9999	-0.42	5	5
FBXW11	0.011	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
CHUK	0.007	0.048	-9999	-0.58	4	4
NF kappa B2 p100/RelB	0.029	0.051	-9999	-0.41	6	6
NFKB1	0.01	0.024	-9999	-0.58	1	1
MAP3K14	0.01	0.024	-9999	-0.58	1	1
NF kappa B1 p50/RelB	0.014	0.032	-9999	-0.37	4	4
RELB	0.009	0.036	-9999	-0.5	3	3
NFKB2	0.01	0.031	-9999	-0.52	2	2
NF kappa B2 p52/RelB	0.013	0.038	-9999	-0.49	3	3
regulation of B cell activation	0.013	0.038	-9999	-0.49	3	3

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.022	0.022	-9999	-0.35	2	2
E-cadherin/beta catenin	0.016	0.018	-9999	-0.42	1	1
CTNNB1	0.011	0	-9999	-10000	0	0
JUP	0.01	0.024	-9999	-0.58	1	1
CDH1	0.01	0.024	-9999	-0.58	1	1

pid_entity	TCGA.QG.A5Z2	TCGA.QG.A5Z1	TCGA.QG.A5YX	TCGA.QG.A5YW
109_MAP3K5	0.044	0.044	0.044	0.044
47_PPARGC1A	0.011	0.011	0.011	0.011
105_BMP4	0.011	0.011	-0.58	0.011
105_BMP6	0.011	0.011	-0.58	0.011
105_BMP7	0.011	0.011	0.011	0.011
105_BMP2	0.011	0.011	0.011	0.011
131_RELN/VLDLR	0.029	0.029	-0.32	0.029
30_TGFB1/TGF beta receptor Type II	0.011	0.011	0.011	0.011
84_STAT5B	-0.14	-0.0064	-0.18	0.037
84_STAT5A	-0.14	-0.0064	-0.18	0.037