Ovarian Serous Cystadenocarcinoma: PARADIGM pathway analysis of mRNA expression and copy number data

Pathway.Name	Avg.Num.Perturbations
PLK2 and PLK4 events	177
FOXM1 transcription factor network	137
TCGA08_p53	99
HIF-1-alpha transcription factor network	94
Ephrin B reverse signaling	93
LPA receptor mediated events	90
Endothelins	88
Syndecan-1-mediated signaling events	87
Osteopontin-mediated events	86
Wnt signaling	84

Pathway.Name	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
PLK2 and PLK4 events	177	532	3	-0.011	0.036	1000	-1000	-0.017	-1000
FOXM1 transcription factor network	137	7014	51	-0.51	0.037	1000	-1000	-0.014	-1000
TCGA08_p53	99	694	7	-0.053	0.038	1000	-1000	-0.009	-1000
HIF-1-alpha transcription factor network	94	7178	76	-0.048	0.087	1000	-1000	0	-1000
Ephrin B reverse signaling	93	4483	48	-0.2	0.079	1000	-1000	-0.051	-1000
LPA receptor mediated events	90	9236	102	-0.043	0.04	1000	-1000	-0.04	-1000
Endothelins	88	8532	96	-0.18	0.04	1000	-1000	-0.021	-1000
Syndecan-1-mediated signaling events	87	2963	34	-0.044	0.04	1000	-1000	-0.003	-1000
Osteopontin-mediated events	86	3294	38	-0.19	0.04	1000	-1000	-0.008	-1000
Wnt signaling	84	592	7	-0.017	0.04	1000	-1000	-0.003	-1000
Nectin adhesion pathway	81	5104	63	-0.088	0.063	1000	-1000	-0.012	-1000
amb2 Integrin signaling	79	6520	82	-0.085	0.081	1000	-1000	-0.016	-1000
PDGFR-alpha signaling pathway	78	3441	44	-0.13	0.049	1000	-1000	-0.022	-1000
TCGA08_retinoblastoma	78	626	8	-0.012	0.03	1000	-1000	-0.004	-1000
Thromboxane A2 receptor signaling	76	8047	105	-0.15	0.069	1000	-1000	-0.02	-1000
TRAIL signaling pathway	74	3597	48	-0.02	0.041	1000	-1000	-0.017	-1000
BARD1 signaling events	72	4124	57	-0.039	0.06	1000	-1000	-0.065	-1000
TCGA08_rtk_signaling	71	1857	26	-0.021	0.039	1000	-1000	-0.02	-1000
Paxillin-dependent events mediated by a4b1	70	2539	36	-0.065	0.067	1000	-1000	-0.052	-1000
Nongenotropic Androgen signaling	69	3630	52	-0.12	0.059	1000	-1000	-0.018	-1000
Signaling events mediated by the Hedgehog family	67	3520	52	-0.066	0.058	1000	-1000	-0.024	-1000
Integrins in angiogenesis	67	5644	84	-0.053	0.054	1000	-1000	-0.017	-1000
Ras signaling in the CD4+ TCR pathway	67	1154	17	-0.007	0.053	1000	-1000	-0.003	-1000
IL1-mediated signaling events	66	4143	62	-0.045	0.072	1000	-1000	-0.017	-1000
IL23-mediated signaling events	66	4018	60	-0.17	0.049	1000	-1000	-0.039	-1000
Signaling events mediated by PTP1B	65	4974	76	-0.059	0.068	1000	-1000	-0.036	-1000
IGF1 pathway	65	3707	57	-0.022	0.065	1000	-1000	-0.016	-1000
IL12-mediated signaling events	64	5608	87	-0.18	0.053	1000	-1000	-0.022	-1000
Fc-epsilon receptor I signaling in mast cells	64	6243	97	-0.081	0.046	1000	-1000	-0.038	-1000
Cellular roles of Anthrax toxin	63	2482	39	-0.082	0.04	1000	-1000	-0.015	-1000
Canonical Wnt signaling pathway	63	3228	51	-0.18	0.092	1000	-1000	-0.011	-1000
Syndecan-4-mediated signaling events	63	4246	67	-0.064	0.043	1000	-1000	-0.031	-1000
Syndecan-2-mediated signaling events	60	4183	69	-0.004	0.062	1000	-1000	-0.013	-1000
IL6-mediated signaling events	60	4553	75	-0.14	0.049	1000	-1000	-0.019	-1000
E-cadherin signaling in keratinocytes	60	2584	43	-0.017	0.052	1000	-1000	-0.007	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	59	5041	85	-0.16	0.049	1000	-1000	-0.028	-1000
IL4-mediated signaling events	59	5408	91	-0.22	0.055	1000	-1000	-0.034	-1000
IL2 signaling events mediated by STAT5	59	1307	22	-0.036	0.047	1000	-1000	-0.006	-1000
a4b1 and a4b7 Integrin signaling	58	294	5	0.031	0.038	1000	-1000	0.037	-1000
FoxO family signaling	58	3748	64	-0.2	0.044	1000	-1000	-0.019	-1000
Noncanonical Wnt signaling pathway	57	1491	26	-0.036	0.04	1000	-1000	-0.038	-1000
HIF-2-alpha transcription factor network	57	2459	43	-0.056	0.069	1000	-1000	-0.079	-1000
TCR signaling in naïve CD8+ T cells	57	5348	93	-0.071	0.076	1000	-1000	-0.027	-1000
BMP receptor signaling	56	4600	81	-0.021	0.071	1000	-1000	-0.001	-1000
IFN-gamma pathway	54	3685	68	-0.045	0.062	1000	-1000	-0.031	-1000
Retinoic acid receptors-mediated signaling	54	3167	58	-0.084	0.061	1000	-1000	-0.003	-1000
Plasma membrane estrogen receptor signaling	54	4644	86	-0.086	0.083	1000	-1000	-0.018	-1000
Paxillin-independent events mediated by a4b1 and a4b7	53	1995	37	-0.019	0.069	1000	-1000	-0.01	-1000
EPHB forward signaling	53	4508	85	-0.057	0.14	1000	-1000	-0.038	-1000
FAS signaling pathway (CD95)	51	2431	47	-0.042	0.053	1000	-1000	-0.024	-1000
BCR signaling pathway	51	5059	99	-0.058	0.068	1000	-1000	-0.034	-1000
ErbB4 signaling events	50	3516	69	-0.068	0.055	1000	-1000	-0.03	-1000
E-cadherin signaling in the nascent adherens junction	50	3870	76	-0.056	0.073	1000	-1000	-0.028	-1000
E-cadherin signaling events	49	248	5	0.035	0.052	1000	-1000	0.037	-1000
Caspase cascade in apoptosis	48	3597	74	-0.097	0.051	1000	-1000	-0.017	-1000
Signaling events mediated by PRL	48	1645	34	-0.017	0.04	1000	-1000	-0.024	-1000
Presenilin action in Notch and Wnt signaling	47	2903	61	-0.16	0.076	1000	-1000	-0.025	-1000
IL2 signaling events mediated by PI3K	47	2731	58	-0.06	0.04	1000	-1000	-0.018	-1000
Class I PI3K signaling events	47	3501	73	-0.016	0.049	1000	-1000	-0.017	-1000
EPO signaling pathway	46	2561	55	-0.001	0.071	1000	-1000	-0.012	-1000
Circadian rhythm pathway	45	992	22	-0.08	0.044	1000	-1000	-0.027	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	45	2046	45	-0.059	0.077	1000	-1000	-0.018	-1000
Stabilization and expansion of the E-cadherin adherens junction	45	3359	74	-0.069	0.065	1000	-1000	-0.052	-1000
Aurora B signaling	45	3051	67	-0.058	0.067	1000	-1000	-0.018	-1000
Arf6 signaling events	44	2734	62	0	0.079	1000	-1000	0	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	44	1455	33	-0.003	0.083	1000	-1000	-0.008	-1000
p75(NTR)-mediated signaling	42	5257	125	-0.069	0.093	1000	-1000	-0.036	-1000
S1P3 pathway	42	1773	42	-0.019	0.053	1000	-1000	-0.003	-1000
PLK1 signaling events	41	3557	85	-0.041	0.051	1000	-1000	-0.019	-1000
Reelin signaling pathway	41	2304	56	-0.016	0.091	1000	-1000	-0.006	-1000
RXR and RAR heterodimerization with other nuclear receptor	41	2157	52	-0.045	0.092	1000	-1000	-0.011	-1000
Regulation of p38-alpha and p38-beta	41	2233	54	-0.032	0.091	1000	-1000	-0.001	-1000
Regulation of Telomerase	41	4239	102	-0.11	0.072	1000	-1000	-0.016	-1000
ErbB2/ErbB3 signaling events	40	2650	65	-0.029	0.047	1000	-1000	-0.04	-1000
Canonical NF-kappaB pathway	40	1570	39	-0.036	0.065	1000	-1000	-0.018	-1000
Regulation of Androgen receptor activity	40	2836	70	-0.087	0.063	1000	-1000	-0.023	-1000
EGFR-dependent Endothelin signaling events	38	799	21	-0.016	0.081	1000	-1000	0	-1000
PDGFR-beta signaling pathway	38	3711	97	-0.039	0.083	1000	-1000	-0.034	-1000
JNK signaling in the CD4+ TCR pathway	37	636	17	-0.004	0.072	1000	-1000	-0.001	-1000
Insulin-mediated glucose transport	37	1203	32	-0.018	0.046	1000	-1000	-0.017	-1000
mTOR signaling pathway	37	1976	53	-0.036	0.059	1000	-1000	-0.015	-1000
FOXA2 and FOXA3 transcription factor networks	36	1667	46	-0.13	0.055	1000	-1000	-0.005	-1000
S1P5 pathway	36	614	17	-0.008	0.04	1000	-1000	-0.021	-1000
Neurotrophic factor-mediated Trk receptor signaling	36	4432	120	-0.054	0.087	1000	-1000	-0.019	-1000
Aurora A signaling	35	2100	60	-0.046	0.064	1000	-1000	-0.017	-1000
p38 MAPK signaling pathway	35	1552	44	-0.035	0.073	1000	-1000	0	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	34	1843	54	-0.017	0.055	1000	-1000	-0.017	-1000
Ceramide signaling pathway	34	2596	76	-0.018	0.079	1000	-1000	-0.017	-1000
ceramide signaling pathway	34	1666	49	-0.034	0.06	1000	-1000	-0.007	-1000
Syndecan-3-mediated signaling events	34	1207	35	-0.011	0.067	1000	-1000	-0.017	-1000
S1P4 pathway	34	855	25	-0.014	0.053	1000	-1000	-0.005	-1000
Arf6 downstream pathway	33	1452	43	-0.036	0.057	1000	-1000	-0.045	-1000
Signaling mediated by p38-gamma and p38-delta	33	495	15	-0.04	0.039	1000	-1000	-0.017	-1000
Regulation of nuclear SMAD2/3 signaling	32	4390	136	-0.093	0.088	1000	-1000	-0.049	-1000
Ephrin A reverse signaling	31	220	7	-0.015	0.039	1000	-1000	-0.008	-1000
Hedgehog signaling events mediated by Gli proteins	31	2054	65	-0.002	0.076	1000	-1000	-0.011	-1000
Class I PI3K signaling events mediated by Akt	31	2134	68	-0.032	0.077	1000	-1000	-0.019	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	31	2629	83	-0.011	0.067	1000	-1000	-0.02	-1000
Signaling events mediated by HDAC Class I	31	3256	104	-0.041	0.076	1000	-1000	-0.039	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	30	710	23	-0.015	0.065	1000	-1000	-0.002	-1000
Atypical NF-kappaB pathway	30	946	31	-0.017	0.04	1000	-1000	-0.017	-1000
Glucocorticoid receptor regulatory network	29	3319	114	-0.1	0.074	1000	-1000	-0.042	-1000
Signaling events regulated by Ret tyrosine kinase	29	2396	82	-0.01	0.093	1000	-1000	-0.022	-1000
Sphingosine 1-phosphate (S1P) pathway	28	804	28	-0.019	0.053	1000	-1000	-0.017	-1000
Insulin Pathway	28	2123	74	-0.026	0.1	1000	-1000	-0.028	-1000
Class IB PI3K non-lipid kinase events	28	84	3	-0.039	0.039	1000	-1000	-0.037	-1000
Coregulation of Androgen receptor activity	27	2076	76	-0.011	0.051	1000	-1000	-0.018	-1000
Nephrin/Neph1 signaling in the kidney podocyte	27	923	34	-0.048	0.084	1000	-1000	-0.047	-1000
Glypican 1 network	27	1342	48	-0.039	0.067	1000	-1000	-0.038	-1000
Signaling events mediated by VEGFR1 and VEGFR2	27	3460	125	-0.02	0.069	1000	-1000	-0.017	-1000
LPA4-mediated signaling events	25	307	12	-0.015	0.045	1000	-1000	-0.013	-1000
IL27-mediated signaling events	25	1310	51	-0.009	0.08	1000	-1000	-0.026	-1000
Alternative NF-kappaB pathway	25	329	13	0	0.093	1000	-1000	0	-1000
Signaling events mediated by HDAC Class II	24	1866	75	-0.036	0.092	1000	-1000	-0.024	-1000
Signaling events mediated by HDAC Class III	24	975	40	-0.062	0.071	1000	-1000	-0.055	-1000
VEGFR1 specific signals	24	1375	56	-0.03	0.045	1000	-1000	-0.02	-1000
Angiopoietin receptor Tie2-mediated signaling	24	2192	88	-0.045	0.075	1000	-1000	-0.047	-1000
Sumoylation by RanBP2 regulates transcriptional repression	23	643	27	-0.031	0.083	1000	-1000	-0.023	-1000
Aurora C signaling	22	160	7	0	0.06	1000	-1000	0	-1000
Signaling mediated by p38-alpha and p38-beta	22	984	44	-0.028	0.052	1000	-1000	-0.009	-1000
Effects of Botulinum toxin	22	573	26	-0.01	0.069	1000	-1000	-0.009	-1000
Calcium signaling in the CD4+ TCR pathway	22	700	31	-0.024	0.082	1000	-1000	-0.028	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	22	1512	68	-0.077	0.094	1000	-1000	-0.03	-1000
Rapid glucocorticoid signaling	22	444	20	-0.01	0.046	1000	-1000	-0.01	-1000
S1P1 pathway	21	784	36	0	0.043	1000	-1000	-0.003	-1000
Arf6 trafficking events	19	1363	71	-0.046	0.05	1000	-1000	-0.038	-1000
Arf1 pathway	19	1071	54	-0.009	0.051	1000	-1000	-0.01	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	17	1326	78	-0.017	0.063	1000	-1000	-0.042	-1000
Glypican 2 network	16	64	4	0.039	0.054	1000	-1000	0.037	-1000
Visual signal transduction: Rods	14	736	52	-0.017	0.097	1000	-1000	-0.006	-1000
Visual signal transduction: Cones	13	520	38	-0.01	0.089	1000	-1000	-0.012	-1000
Total	6285	347164	7203	-7.1	8.2	131000	-131000	-2.6	-131000

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.026	0.02	-9999	0	0	207	207
PLK4	0.036	0.014	-9999	0	0	74	74
regulation of centriole replication	-0.011	0.01	0	251	-9999	0	251

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.34	0.6	-10000	0	-1.1	159	159
PLK1	-0.045	0.3	-10000	0	-1.2	32	32
BIRC5	-0.053	0.33	-10000	0	-1.3	33	33
HSPA1B	-0.34	0.6	-10000	0	-1.1	177	177
MAP2K1	0.003	0.07	-10000	0	-10000	0	0
BRCA2	-0.35	0.61	-10000	0	-1.1	170	170
FOXM1	-0.51	0.88	-10000	0	-1.6	176	176
XRCC1	-0.34	0.6	0.75	1	-1.1	168	169
FOXM1B/p19	-0.43	0.66	-10000	0	-1.3	179	179
Cyclin D1/CDK4	-0.35	0.56	-10000	0	-1	183	183
CDC2	-0.4	0.68	-10000	0	-1.3	181	181
TGFA	-0.32	0.52	-10000	0	-0.98	169	169
SKP2	-0.34	0.61	-10000	0	-1.1	167	167
CCNE1	0.018	0.028	-10000	0	-0.033	66	66
CKS1B	-0.34	0.61	-10000	0	-1.1	168	168
RB1	-0.31	0.47	-10000	0	-0.94	165	165
FOXM1C/SP1	-0.43	0.71	-10000	0	-1.3	178	178
AURKB	-0.11	0.41	-10000	0	-1.2	61	61
CENPF	-0.38	0.63	-10000	0	-1.2	182	182
CDK4	0.008	0.044	0.11	1	-0.038	188	189
MYC	-0.33	0.48	-10000	0	-0.94	177	177
CHEK2	0.006	0.065	-10000	0	-10000	0	0
ONECUT1	-0.35	0.58	-10000	0	-1.1	170	170
CDKN2A	0.026	0.02	0.089	2	-0.033	7	9
LAMA4	-0.38	0.63	-10000	0	-1.2	186	186
FOXM1B/HNF6	-0.44	0.71	-10000	0	-1.4	170	170
FOS	-0.42	0.65	-10000	0	-1.2	214	214
SP1	0.035	0.022	-10000	0	-0.032	48	48
CDC25B	-0.34	0.6	-10000	0	-1.1	167	167
response to radiation	-0.006	0.036	0.088	6	-10000	0	6
CENPB	-0.34	0.6	-10000	0	-1.1	163	163
CENPA	-0.35	0.6	-10000	0	-1.1	167	167
NEK2	-0.36	0.61	-10000	0	-1.2	169	169
HIST1H2BA	-0.34	0.6	-10000	0	-1.1	164	164
CCNA2	0.023	0.03	-10000	0	-0.013	201	201
EP300	0.036	0.014	-10000	0	0	69	69
CCNB1/CDK1	-0.48	0.78	-10000	0	-1.5	175	175
CCNB2	-0.38	0.62	-10000	0	-1.2	178	178
CCNB1	-0.38	0.66	-10000	0	-1.2	169	169
ETV5	-0.35	0.64	-10000	0	-1.2	185	185
ESR1	-0.38	0.62	-10000	0	-1.1	189	189
CCND1	-0.36	0.56	-10000	0	-1	183	183
GSK3A	0.005	0.061	0.16	1	-10000	0	1
Cyclin A-E1/CDK1-2	-0.009	0.1	-10000	0	-0.16	116	116
CDK2	0.027	0.029	-10000	0	-0.02	138	138
G2/M transition of mitotic cell cycle	-0.007	0.043	0.099	5	-10000	0	5
FOXM1B/Cbp/p300	-0.39	0.66	-10000	0	-1.2	174	174
GAS1	-0.35	0.6	-10000	0	-1.1	171	171
MMP2	-0.42	0.65	-10000	0	-1.2	212	212
RB1/FOXM1C	-0.4	0.59	0.67	1	-1.1	180	181
CREBBP	0.037	0.012	-10000	0	0	53	53

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.007	0.005	0	167	-10000	0	167
TP53	-0.052	0.12	0.18	12	-0.24	143	155
Senescence	-0.053	0.12	0.18	12	-0.24	145	157
Apoptosis	-0.053	0.12	0.18	12	-0.24	145	157
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	-0.004	0.044	0.3	11	-10000	0	11
MDM4	0.038	0.012	-10000	0	0	47	47

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	0.046	0.34	0.56	50	-0.54	81	131
HDAC7	-0.001	0.004	-10000	0	-0.039	1	1
HIF1A/ARNT/Cbp/p300/Src-1	0.018	0.31	0.57	3	-0.58	57	60
SMAD4	0.038	0.011	-10000	0	0	43	43
ID2	0.046	0.34	0.56	51	-0.54	81	132
AP1	0.006	0.084	-10000	0	-0.14	118	118
ABCG2	0.042	0.34	0.56	49	-0.54	80	129
HIF1A	0.028	0.11	0.2	43	-0.14	78	121
TFF3	0.024	0.32	0.56	40	-0.54	80	120
GATA2	0.04	0.018	-10000	0	-0.056	11	11
AKT1	0.042	0.098	0.22	32	-0.12	61	93
response to hypoxia	0.004	0.07	0.15	36	-0.12	55	91
MCL1	0.034	0.33	0.55	45	-0.55	80	125
NDRG1	0	0.3	0.53	30	-0.56	70	100
SERPINE1	0	0.31	0.55	30	-0.55	78	108
FECH	0.043	0.34	0.56	50	-0.55	78	128
FURIN	0.046	0.34	0.56	52	-0.54	80	132
NCOA2	0.038	0.014	-10000	0	-0.001	61	61
EP300	0.046	0.12	0.29	48	-0.25	22	70
HMOX1	0.032	0.33	0.55	43	-0.55	81	124
BHLHE40	-0.025	0.29	0.46	50	-0.53	82	132
BHLHE41	-0.025	0.29	0.46	50	-0.53	82	132
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.087	0.15	0.35	13	-0.21	35	48
ENG	0.032	0.12	0.28	26	-0.21	24	50
JUN	0.035	0.018	-10000	0	-0.042	10	10
RORA	0.045	0.34	0.56	49	-0.54	80	129
ABCB1	0.014	0.093	-10000	0	-0.55	4	4
TFRC	0.004	0.31	0.55	32	-0.55	79	111
CXCR4	0.019	0.33	0.55	42	-0.55	83	125
TF	0.04	0.33	0.56	50	-0.54	80	130
CITED2	0.042	0.33	0.55	49	-0.54	81	130
HIF1A/ARNT	0.018	0.37	-10000	0	-0.68	56	56
LDHA	-0.048	0.29	-10000	0	-0.93	50	50
ETS1	0.024	0.33	0.55	39	-0.57	78	117
PGK1	0.045	0.34	0.56	50	-0.56	81	131
NOS2	-0.025	0.29	0.46	50	-0.53	82	132
ITGB2	0.025	0.34	0.55	41	-0.56	85	126
ALDOA	0.052	0.34	0.56	54	-0.54	81	135
Cbp/p300/CITED2	0.017	0.33	0.55	32	-0.61	67	99
FOS	0.026	0.022	-10000	0	-0.001	206	206
HK2	0.045	0.34	0.56	51	-0.55	79	130
SP1	0.047	0.009	-10000	0	-10000	0	0
GCK	0.067	0.16	0.53	8	-0.41	1	9
HK1	0.049	0.34	0.55	53	-0.54	81	134
NPM1	0.051	0.34	0.56	53	-0.54	82	135
EGLN1	0.049	0.33	0.55	54	-0.54	80	134
CREB1	0.034	0.042	-10000	0	-0.11	40	40
PGM1	0.038	0.34	0.56	46	-0.56	81	127
SMAD3	0.04	0.009	-10000	0	0	23	23
EDN1	0.037	0.21	0.46	5	-1	12	17
IGFBP1	0.051	0.34	0.56	53	-0.54	80	133
VEGFA	-0.009	0.26	0.44	34	-0.5	66	100
HIF1A/JAB1	0.035	0.099	0.19	15	-0.14	87	102
CP	-0.006	0.31	0.54	36	-0.56	80	116
CXCL12	-0.012	0.31	0.56	27	-0.55	83	110
COPS5	0.036	0.015	-10000	0	-0.001	80	80
SMAD3/SMAD4	0.052	0.032	-10000	0	-0.13	10	10
BNIP3	0.026	0.33	0.56	41	-0.57	77	118
EGLN3	-0.006	0.32	0.55	31	-0.56	88	119
CA9	-0.006	0.31	0.55	28	-0.54	82	110
TERT	0.036	0.33	0.55	46	-0.54	78	124
ENO1	0.048	0.34	0.56	51	-0.55	80	131
PFKL	0.051	0.34	0.56	52	-0.54	81	133
NCOA1	0.04	0.009	-10000	0	-0.001	23	23
ADM	0.011	0.32	0.56	27	-0.55	83	110
ARNT	0.027	0.095	0.19	36	-0.12	69	105
HNF4A	0.041	0.011	-10000	0	-10000	0	0
ADFP	0.01	0.32	0.55	36	-0.55	86	122
SLC2A1	0.013	0.29	0.48	32	-0.52	70	102
LEP	0.049	0.34	0.56	51	-0.55	78	129
HIF1A/ARNT/Cbp/p300	0.01	0.31	0.57	3	-0.6	57	60
EPO	0.039	0.28	0.52	22	-0.53	52	74
CREBBP	0.051	0.12	0.29	51	-0.22	16	67
HIF1A/ARNT/Cbp/p300/HDAC7	0.002	0.3	0.54	3	-0.59	58	61
PFKFB3	0.041	0.34	0.56	49	-0.56	79	128
NT5E	-0.027	0.31	0.54	22	-0.56	89	111

×

Ephrin B reverse signaling

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
EFNB2	0.031	0.018	-10000	0	0	139	139
EPHB2	0.042	0.013	-10000	0	0	38	38
EFNB1	0.001	0.024	0.026	246	-10000	0	246
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.075	0.066	-10000	0	-0.12	19	19
Ephrin B2/EPHB1-2	0.039	0.068	-10000	0	-0.1	78	78
neuron projection morphogenesis	0.051	0.052	-10000	0	-0.11	24	24
Ephrin B1/EPHB1-2/Tiam1	0.069	0.061	0.2	1	-0.11	29	30
DNM1	0.041	0.011	-10000	0	0	33	33
cell-cell signaling	0.003	0.005	-10000	0	-10000	0	0
MAP2K4	-0.14	0.21	0.23	3	-0.46	159	162
YES1	-0.19	0.33	-10000	0	-0.7	157	157
Ephrin B1/EPHB1-2/NCK2	0.079	0.05	0.19	2	-0.11	15	17
PI3K	-0.1	0.22	-10000	0	-0.44	159	159
mol:GDP	0.067	0.059	0.19	1	-0.11	29	30
ITGA2B	0.04	0.008	-10000	0	0	22	22
endothelial cell proliferation	0.024	0.06	-10000	0	-0.11	82	82
FYN	-0.2	0.33	-10000	0	-0.7	159	159
MAP3K7	-0.14	0.23	0.22	3	-0.49	155	158
FGR	-0.19	0.32	-10000	0	-0.68	161	161
TIAM1	0.036	0.013	-10000	0	0	66	66
PIK3R1	0.034	0.016	-10000	0	0	99	99
RGS3	0.04	0.007	-10000	0	0	15	15
cell adhesion	-0.11	0.21	-10000	0	-0.41	159	159
LYN	-0.19	0.32	-10000	0	-0.7	155	155
Ephrin B1/EPHB1-2/Src Family Kinases	-0.18	0.29	-10000	0	-0.63	160	160
Ephrin B1/EPHB1-2	-0.14	0.24	-10000	0	-0.53	149	149
SRC	-0.18	0.32	-10000	0	-0.69	158	158
ITGB3	0.032	0.017	-10000	0	0	116	116
EPHB1	0.04	0.013	-10000	0	0	50	50
EPHB4	0.039	0.008	-10000	0	0	23	23
RAC1	0.039	0.009	-10000	0	0	28	28
Ephrin B2/EPHB4	0.025	0.06	-10000	0	-0.11	82	82
alphaIIb/beta3 Integrin	0.039	0.05	-10000	0	-0.13	35	35
BLK	-0.2	0.32	-10000	0	-0.7	158	158
HCK	-0.19	0.32	-10000	0	-0.69	155	155
regulation of stress fiber formation	-0.076	0.049	0.11	15	-0.19	2	17
MAPK8	-0.13	0.21	0.21	4	-0.44	160	164
Ephrin B1/EPHB1-2/RGS3	0.079	0.05	0.19	2	-0.11	15	17
endothelial cell migration	-0.11	0.18	0.19	5	-0.41	145	150
NCK2	0.041	0.004	-10000	0	0	6	6
PTPN13	0.022	0.022	-10000	0	0	271	271
regulation of focal adhesion formation	-0.076	0.049	0.11	15	-0.19	2	17
chemotaxis	-0.076	0.049	0.11	15	-0.19	2	17
PIK3CA	0.029	0.019	-10000	0	0	166	166
Rac1/GTP	0.064	0.059	-10000	0	-0.11	22	22
angiogenesis	-0.14	0.24	-10000	0	-0.53	153	153
LCK	-0.19	0.32	-10000	0	-0.68	161	161

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.019	0.078	-10000	0	-0.13	109	109
NF kappa B1 p50/RelA/I kappa B alpha	-0.009	0.11	0.21	4	-0.22	67	71
AP1	-0.026	0.067	-10000	0	-0.12	170	170
mol:PIP3	-0.035	0.056	-10000	0	-0.13	122	122
AKT1	0	0.091	0.24	14	-0.24	13	27
PTK2B	-0.043	0.1	0.12	3	-0.18	172	175
RHOA	0.002	0.06	0.18	1	-0.31	9	10
PIK3CB	0.034	0.016	-10000	0	0	95	95
mol:Ca2+	-0.009	0.05	0.19	8	-0.14	22	30
MAGI3	0.039	0.009	-10000	0	0	30	30
RELA	0.04	0.006	-10000	0	0	10	10
apoptosis	0.002	0.068	0.072	119	-0.14	94	213
HRAS/GDP	0.029	0.007	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.042	0.1	0.19	17	-0.2	108	125
NF kappa B1 p50/RelA	-0.03	0.075	0.1	2	-0.16	112	114
endothelial cell migration	-0.041	0.12	-10000	0	-0.29	100	100
ADCY4	-0.021	0.096	0.14	8	-0.19	107	115
ADCY5	-0.019	0.095	0.15	7	-0.19	106	113
ADCY6	-0.021	0.096	0.15	7	-0.2	106	113
ADCY7	-0.02	0.095	0.15	7	-0.19	102	109
ADCY1	-0.02	0.096	0.15	7	-0.2	106	113
ADCY2	-0.016	0.093	0.13	12	-0.19	100	112
ADCY3	-0.021	0.097	0.14	7	-0.2	108	115
ADCY8	-0.006	0.088	0.12	28	-0.18	89	117
ADCY9	-0.024	0.099	0.14	8	-0.2	110	118
GSK3B	-0.041	0.11	0.21	14	-0.18	167	181
arachidonic acid secretion	-0.029	0.097	0.14	4	-0.19	124	128
GNG2	0.039	0.009	-10000	0	0	29	29
TRIP6	0.013	0.048	-10000	0	-0.24	15	15
GNAO1	0.007	0.071	0.091	114	-0.14	85	199
HRAS	0.039	0.01	-10000	0	0	31	31
NFKBIA	-0.032	0.092	0.18	7	-0.24	56	63
GAB1	0.037	0.013	-10000	0	0	58	58
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.008	0.26	-10000	0	-0.88	43	43
JUN	0.036	0.014	-10000	0	0	76	76
LPA/LPA2/NHERF2	0.014	0.037	-10000	0	-0.062	96	96
TIAM1	-0.032	0.29	-10000	0	-1	43	43
PIK3R1	0.034	0.016	-10000	0	0	99	99
mol:IP3	-0.004	0.044	0.19	9	-0.14	14	23
PLCB3	0.014	0.044	0.17	10	-0.062	95	105
FOS	0.026	0.02	-10000	0	0	201	201
positive regulation of mitosis	-0.029	0.097	0.14	4	-0.19	124	128
LPA/LPA1-2-3	-0.017	0.05	-10000	0	-0.12	101	101
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.036	0.013	-10000	0	0	65	65
stress fiber formation	-0.009	0.096	-10000	0	-0.25	38	38
GNAZ	0.006	0.074	0.092	115	-0.14	90	205
EGFR/PI3K-beta/Gab1	-0.024	0.065	-10000	0	-0.13	123	123
positive regulation of dendritic cell cytokine production	-0.017	0.049	-10000	0	-0.12	101	101
LPA/LPA2/MAGI-3	0.015	0.037	-10000	0	-0.06	98	98
ARHGEF1	0.005	0.073	0.2	7	-0.13	90	97
GNAI2	0.006	0.076	0.092	121	-0.14	98	219
GNAI3	0.003	0.08	0.092	117	-0.15	99	216
GNAI1	0.003	0.079	0.092	114	-0.16	91	205
LPA/LPA3	-0.01	0.026	-10000	0	-0.064	101	101
LPA/LPA2	-0.01	0.026	-10000	0	-0.064	101	101
LPA/LPA1	-0.025	0.067	-10000	0	-0.17	101	101
HB-EGF/EGFR	0.023	0.052	-10000	0	-0.13	49	49
HBEGF	-0.014	0.01	-10000	0	-10000	0	0
mol:DAG	-0.004	0.044	0.19	9	-0.14	14	23
cAMP biosynthetic process	-0.024	0.098	0.16	9	-0.19	103	112
NFKB1	0.036	0.013	-10000	0	0	66	66
SRC	0.039	0.009	-10000	0	0	28	28
GNB1	0.039	0.01	-10000	0	0	33	33
LYN	-0.025	0.095	0.2	10	-0.23	58	68
GNAQ	0.008	0.032	0.044	116	-0.053	102	218
LPAR2	0	0.001	-10000	0	-10000	0	0
LPAR3	0	0	-10000	0	-10000	0	0
LPAR1	-0.017	0.041	-10000	0	-0.1	101	101
IL8	-0.024	0.17	0.26	4	-0.38	83	87
PTK2	0.007	0.063	0.096	84	-0.12	78	162
Rac1/GDP	0.029	0.009	-10000	0	-0.12	1	1
CASP3	0.002	0.068	0.072	117	-0.14	94	211
EGFR	0.036	0.014	-10000	0	0	67	67
PLCG1	0.005	0.036	-10000	0	-0.094	27	27
PLD2	0.015	0.066	0.095	118	-0.12	90	208
G12/G13	0.02	0.077	-10000	0	-0.13	104	104
PI3K-beta	-0.023	0.072	-10000	0	-0.21	38	38
cell migration	-0.007	0.086	-10000	0	-0.25	43	43
SLC9A3R2	0.037	0.012	-10000	0	0	54	54
PXN	-0.01	0.098	-10000	0	-0.25	38	38
HRAS/GTP	-0.029	0.099	0.14	4	-0.19	123	127
RAC1	0.039	0.009	-10000	0	0	28	28
MMP9	0.028	0.019	-10000	0	0	169	169
PRKCE	0.039	0.009	-10000	0	0	28	28
PRKCD	-0.018	0.057	0.18	10	-0.16	24	34
Gi(beta/gamma)	-0.023	0.1	0.16	4	-0.19	123	127
mol:LPA	-0.017	0.041	-10000	0	-0.1	101	101
TRIP6/p130 Cas/FAK1/Paxillin	-0.003	0.1	0.19	3	-0.2	75	78
MAPKKK cascade	-0.029	0.097	0.14	4	-0.19	124	128
contractile ring contraction involved in cytokinesis	0.001	0.062	0.16	2	-0.31	10	12
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	0.008	0.033	0.044	116	-0.052	109	225
GNA15	0.008	0.031	0.043	108	-0.054	91	199
GNA12	0.039	0.01	-10000	0	0	33	33
GNA13	0.039	0.008	-10000	0	0	23	23
MAPT	-0.042	0.1	0.19	17	-0.2	108	125
GNA11	0.008	0.031	0.043	108	-0.054	95	203
Rac1/GTP	-0.011	0.27	-10000	0	-0.93	43	43
MMP2	-0.042	0.12	-10000	0	-0.29	100	100

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.01	0.14	0.22	29	-0.24	118	147
PTK2B	0.034	0.016	-10000	0	0	97	97
mol:Ca2+	-0.032	0.2	-10000	0	-0.5	45	45
EDN1	-0.009	0.1	0.22	7	-0.18	126	133
EDN3	0.037	0.013	-10000	0	0	60	60
EDN2	0.037	0.012	-10000	0	0	52	52
HRAS/GDP	-0.053	0.19	0.26	2	-0.35	113	115
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.031	0.14	0.22	1	-0.27	104	105
ADCY4	0.006	0.13	0.21	63	-0.23	72	135
ADCY5	0.006	0.13	0.21	55	-0.23	72	127
ADCY6	0.006	0.14	0.21	62	-0.23	74	136
ADCY7	0.005	0.14	0.21	55	-0.23	73	128
ADCY1	0.006	0.14	0.21	57	-0.23	73	130
ADCY2	0.005	0.13	0.22	47	-0.23	61	108
ADCY3	0.005	0.14	0.21	65	-0.24	73	138
ADCY8	-0.004	0.1	0.21	28	-0.23	48	76
ADCY9	0.004	0.14	0.21	56	-0.23	76	132
arachidonic acid secretion	-0.1	0.26	0.26	1	-0.49	136	137
ETB receptor/Endothelin-1/Gq/GTP	-0.004	0.11	-10000	0	-0.24	61	61
GNAO1	0.035	0.015	-10000	0	0	85	85
HRAS	0.039	0.01	-10000	0	0	31	31
ETA receptor/Endothelin-1/G12/GTP	-0.011	0.13	0.34	6	-0.21	126	132
ETA receptor/Endothelin-1/Gs/GTP	-0.008	0.12	0.32	7	-0.2	122	129
mol:GTP	0	0.006	-10000	0	-0.025	3	3
COL3A1	-0.06	0.16	0.27	7	-0.36	116	123
EDNRB	0.021	0.053	0.091	5	-0.086	95	100
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.01	0.14	0.28	9	-0.25	99	108
CYSLTR1	-0.021	0.14	0.25	8	-0.26	113	121
SLC9A1	-0.018	0.085	0.2	7	-0.16	98	105
mol:GDP	-0.067	0.19	0.25	2	-0.36	116	118
SLC9A3	-0.026	0.19	-10000	0	-0.55	31	31
RAF1	-0.077	0.22	0.26	9	-0.4	140	149
JUN	-0.073	0.29	-10000	0	-0.81	56	56
JAK2	-0.013	0.14	0.22	28	-0.24	114	142
mol:IP3	-0.026	0.15	0.2	2	-0.31	81	83
ETA receptor/Endothelin-1	-0.037	0.15	0.38	6	-0.27	135	141
PLCB1	0.033	0.016	-10000	0	0	106	106
PLCB2	0.037	0.014	-10000	0	-0.006	45	45
ETA receptor/Endothelin-3	0.015	0.084	0.19	7	-0.12	118	125
FOS	-0.14	0.36	0.33	1	-0.82	109	110
Gai/GDP	-0.018	0.21	-10000	0	-0.71	44	44
CRK	0.038	0.012	-10000	0	0	49	49
mol:Ca ++	-0.035	0.19	0.25	27	-0.34	116	143
BCAR1	0.036	0.013	-10000	0	0	65	65
PRKCB1	-0.03	0.15	0.22	7	-0.3	84	91
GNAQ	0.034	0.022	-10000	0	-0.039	30	30
GNAZ	0.038	0.011	-10000	0	0	46	46
GNAL	0.04	0.008	-10000	0	0	22	22
Gs family/GDP	-0.052	0.18	0.25	2	-0.34	111	113
ETA receptor/Endothelin-1/Gq/GTP	-0.022	0.14	0.21	5	-0.28	84	89
MAPK14	-0.023	0.11	0.23	2	-0.25	75	77
TRPC6	-0.035	0.2	-10000	0	-0.52	44	44
GNAI2	0.04	0.006	-10000	0	0	13	13
GNAI3	0.038	0.011	-10000	0	0	45	45
GNAI1	0.034	0.015	-10000	0	0	93	93
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.018	0.12	-10000	0	-0.25	79	79
ETB receptor/Endothelin-2	0.031	0.054	-10000	0	-0.07	85	85
ETB receptor/Endothelin-3	0.033	0.051	-10000	0	-0.065	82	82
ETB receptor/Endothelin-1	0	0.1	0.2	5	-0.19	100	105
MAPK3	-0.13	0.34	0.32	3	-0.76	112	115
MAPK1	-0.14	0.35	0.32	3	-0.75	117	120
Rac1/GDP	-0.054	0.19	0.26	2	-0.35	111	113
cAMP biosynthetic process	0.034	0.13	0.24	43	-0.23	29	72
MAPK8	-0.052	0.23	-10000	0	-0.54	70	70
SRC	0.039	0.009	-10000	0	0	28	28
ETB receptor/Endothelin-1/Gi/GTP	-0.01	0.11	-10000	0	-0.26	58	58
p130Cas/CRK/Src/PYK2	-0.06	0.2	0.36	1	-0.4	91	92
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.054	0.19	0.27	1	-0.35	112	113
COL1A2	-0.079	0.22	0.28	6	-0.49	106	112
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.012	0.088	0.18	8	-0.13	125	133
mol:DAG	-0.026	0.15	0.2	2	-0.31	81	83
MAP2K2	-0.1	0.27	0.29	4	-0.55	124	128
MAP2K1	-0.11	0.28	0.29	4	-0.56	125	129
EDNRA	-0.004	0.1	0.22	8	-0.17	134	142
positive regulation of muscle contraction	-0.016	0.12	0.21	24	-0.24	81	105
Gq family/GDP	-0.019	0.19	-10000	0	-0.32	110	110
HRAS/GTP	-0.055	0.18	0.24	3	-0.33	122	125
PRKCH	-0.034	0.15	0.2	1	-0.3	91	92
RAC1	0.039	0.009	-10000	0	0	28	28
PRKCA	-0.031	0.15	0.23	4	-0.31	85	89
PRKCB	-0.03	0.15	0.19	2	-0.29	93	95
PRKCE	-0.032	0.15	0.28	5	-0.3	89	94
PRKCD	-0.033	0.15	0.24	2	-0.3	87	89
PRKCG	-0.033	0.15	0.23	6	-0.3	89	95
regulation of vascular smooth muscle contraction	-0.18	0.44	-10000	0	-1	106	106
PRKCQ	-0.034	0.15	0.26	5	-0.31	88	93
PLA2G4A	-0.12	0.28	-10000	0	-0.53	136	136
GNA14	0.035	0.021	-10000	0	-0.038	33	33
GNA15	0.033	0.022	-10000	0	-0.035	29	29
GNA12	0.039	0.01	-10000	0	0	33	33
GNA11	0.033	0.021	-10000	0	-0.012	91	91
Rac1/GTP	-0.011	0.13	0.34	6	-0.21	125	131
MMP1	0.023	0.12	0.3	21	-0.58	9	30

×

Syndecan-1-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.036	0.014	-10000	0	0	69	69
CCL5	0.029	0.019	-10000	0	0	160	160
SDCBP	0.035	0.014	-10000	0	0	77	77
FGFR/FGF2/Syndecan-1	-0.018	0.12	0.2	14	-0.32	44	58
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	-0.017	0.14	0.23	15	-0.3	59	74
Syndecan-1/Syntenin	-0.017	0.14	0.23	21	-0.29	67	88
MAPK3	-0.025	0.13	0.2	22	-0.28	64	86
HGF/MET	0.013	0.074	-10000	0	-0.13	102	102
TGFB1/TGF beta receptor Type II	0.036	0.014	-10000	0	0	69	69
BSG	0.036	0.014	-10000	0	0	74	74
keratinocyte migration	-0.016	0.14	0.23	15	-0.3	59	74
Syndecan-1/RANTES	-0.021	0.15	0.22	21	-0.29	79	100
Syndecan-1/CD147	-0.004	0.15	0.26	17	-0.29	63	80
Syndecan-1/Syntenin/PIP2	-0.019	0.14	0.21	19	-0.28	67	86
LAMA5	0.036	0.014	-10000	0	0	72	72
positive regulation of cell-cell adhesion	-0.019	0.13	0.21	16	-0.28	67	83
MMP7	0.016	0.02	-10000	0	0	333	333
HGF	0.039	0.009	-10000	0	0	27	27
Syndecan-1/CASK	-0.044	0.12	0.15	3	-0.29	65	68
Syndecan-1/HGF/MET	-0.021	0.15	0.26	14	-0.27	85	99
regulation of cell adhesion	-0.033	0.12	0.19	19	-0.28	59	78
HPSE	0.035	0.014	-10000	0	0	79	79
positive regulation of cell migration	-0.018	0.12	0.2	14	-0.32	44	58
SDC1	-0.022	0.12	0.17	4	-0.34	38	42
Syndecan-1/Collagen	-0.018	0.12	0.2	14	-0.32	44	58
PPIB	0.04	0.007	-10000	0	0	18	18
MET	0.027	0.02	-10000	0	0	191	191
PRKACA	0.035	0.015	-10000	0	0	84	84
MMP9	0.028	0.019	-10000	0	0	169	169
MAPK1	-0.023	0.13	0.2	22	-0.28	62	84
homophilic cell adhesion	-0.018	0.13	0.2	22	-0.31	50	72
MMP1	0.03	0.018	-10000	0	0	151	151

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.013	0.13	0.21	7	-0.22	114	121
NF kappa B1 p50/RelA/I kappa B alpha	-0.043	0.18	0.28	1	-0.35	117	118
alphaV/beta3 Integrin/Osteopontin/Src	-0.007	0.11	-10000	0	-0.18	133	133
AP1	-0.047	0.18	0.27	2	-0.28	150	152
ILK	-0.029	0.11	0.2	9	-0.23	72	81
bone resorption	-0.042	0.1	0.2	2	-0.25	54	56
PTK2B	0.034	0.016	-10000	0	0	97	97
PYK2/p130Cas	0.006	0.12	-10000	0	-0.2	81	81
ITGAV	0.025	0.033	-10000	0	-0.049	64	64
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.028	0.067	-10000	0	-0.14	68	68
alphaV/beta3 Integrin/Osteopontin	-0.005	0.12	-10000	0	-0.17	157	157
MAP3K1	-0.028	0.11	0.2	8	-0.24	70	78
JUN	0.036	0.015	-10000	0	0	76	76
MAPK3	-0.05	0.14	0.19	12	-0.28	113	125
MAPK1	-0.047	0.14	0.19	12	-0.28	109	121
Rac1/GDP	0.029	0.009	-10000	0	-0.12	1	1
NFKB1	0.036	0.013	-10000	0	0	66	66
MAPK8	-0.034	0.1	0.19	9	-0.24	73	82
ITGB3	0.023	0.034	-10000	0	-0.049	76	76
NFKBIA	-0.065	0.17	0.19	9	-0.35	114	123
FOS	0.026	0.02	-10000	0	0	201	201
CD44	0.034	0.015	-10000	0	0	90	90
CHUK	0.038	0.011	-10000	0	0	46	46
PLAU	-0.19	0.42	-10000	0	-1	104	104
NF kappa B1 p50/RelA	-0.03	0.2	0.29	1	-0.39	109	110
BCAR1	0.036	0.013	-10000	0	0	65	65
RELA	0.04	0.006	-10000	0	0	10	10
alphaV beta3 Integrin	0.004	0.091	-10000	0	-0.14	130	130
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.03	0.1	0.19	12	-0.23	75	87
VAV3	-0.042	0.1	0.17	9	-0.23	88	97
MAP3K14	-0.027	0.12	0.2	10	-0.23	109	119
ROCK2	0.037	0.013	-10000	0	0	58	58
SPP1	0.025	0.032	-10000	0	-0.051	51	51
RAC1	0.039	0.009	-10000	0	0	28	28
Rac1/GTP	-0.037	0.11	0.18	10	-0.22	86	96
MMP2	-0.089	0.14	0.22	2	-0.32	124	126

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.017	0.093	-9999	-0.28	38	38
FZD6	0.029	0.019	-9999	0	162	162
WNT6	0.04	0.006	-9999	0	13	13
WNT4	0.04	0.008	-9999	0	19	19
FZD3	0.03	0.019	-9999	0	153	153
WNT5A	0.034	0.015	-9999	0	89	89
WNT11	0.032	0.017	-9999	0	118	118

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.036	0.013	-10000	0	0	65	65
alphaV beta3 Integrin	0.014	0.078	-10000	0	-0.15	93	93
PTK2	-0.047	0.14	-10000	0	-0.31	100	100
positive regulation of JNK cascade	-0.038	0.15	-10000	0	-0.28	106	106
CDC42/GDP	-0.048	0.2	-10000	0	-0.36	131	131
Rac1/GDP	-0.05	0.2	-10000	0	-0.36	126	126
RAP1B	0.037	0.012	-10000	0	0	54	54
RAP1A	0.039	0.01	-10000	0	0	35	35
CTNNB1	0.039	0.01	-10000	0	0	32	32
CDC42/GTP	-0.044	0.18	-10000	0	-0.34	105	105
nectin-3/I-afadin	0.011	0.073	-10000	0	-0.14	93	93
RAPGEF1	-0.065	0.18	-10000	0	-0.37	126	126
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.073	0.2	-10000	0	-0.41	129	129
PDGFB-D/PDGFRB	0.036	0.013	-10000	0	0	65	65
TLN1	-0.036	0.08	0.19	1	-0.24	55	56
Rap1/GTP	-0.048	0.14	-10000	0	-0.29	124	124
IQGAP1	0.036	0.013	-10000	0	0	66	66
Rap1/GTP/I-afadin	0.043	0.063	-10000	0	-0.11	61	61
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.011	0.073	-10000	0	-0.14	93	93
PVR	0.038	0.011	-10000	0	0	39	39
Necl-5(dimer)	0.038	0.011	-10000	0	0	39	39
mol:GDP	-0.078	0.22	-10000	0	-0.43	131	131
MLLT4	0.033	0.016	-10000	0	0	109	109
PIK3CA	0.029	0.019	-10000	0	0	166	166
PI3K	0.022	0.086	-10000	0	-0.12	90	90
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.042	0.043	-10000	0	-0.13	22	22
positive regulation of lamellipodium assembly	-0.047	0.16	-10000	0	-0.3	115	115
PVRL1	0.04	0.008	-10000	0	0	22	22
PVRL3	0.029	0.019	-10000	0	0	158	158
PVRL2	0.037	0.012	-10000	0	0	51	51
PIK3R1	0.034	0.016	-10000	0	0	99	99
CDH1	0.035	0.014	-10000	0	0	79	79
CLDN1	0.022	0.021	-10000	0	0	249	249
JAM-A/CLDN1	0.011	0.087	-10000	0	-0.12	124	124
SRC	-0.088	0.21	-10000	0	-0.44	130	130
ITGB3	0.032	0.017	-10000	0	0	116	116
nectin-1(dimer)/I-afadin/I-afadin	0.042	0.043	-10000	0	-0.13	22	22
FARP2	-0.07	0.22	-10000	0	-0.46	90	90
RAC1	0.039	0.009	-10000	0	0	28	28
CTNNA1	0.039	0.01	-10000	0	0	31	31
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.024	0.075	-10000	0	-0.12	92	92
nectin-1/I-afadin	0.042	0.043	-10000	0	-0.13	22	22
nectin-2/I-afadin	0.038	0.047	-10000	0	-0.14	27	27
RAC1/GTP/IQGAP1/filamentous actin	0.039	0.045	-10000	0	-0.11	40	40
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.026	0.074	-10000	0	-0.12	89	89
CDC42/GTP/IQGAP1/filamentous actin	0.039	0.046	-10000	0	-0.11	42	42
F11R	0.039	0.008	-10000	0	0	24	24
positive regulation of filopodium formation	-0.038	0.15	-10000	0	-0.28	106	106
alphaV/beta3 Integrin/Talin	-0.033	0.11	0.26	1	-0.22	95	96
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.038	0.047	-10000	0	-0.14	27	27
nectin-2(dimer)/I-afadin/I-afadin	0.038	0.047	-10000	0	-0.14	27	27
PIP5K1C	-0.03	0.083	-10000	0	-0.17	109	109
VAV2	-0.088	0.24	-10000	0	-0.48	109	109
RAP1/GDP	-0.046	0.19	-10000	0	-0.34	128	128
ITGAV	0.033	0.017	-10000	0	0	110	110
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.022	0.075	-10000	0	-0.12	94	94
nectin-3(dimer)/I-afadin/I-afadin	0.011	0.073	-10000	0	-0.14	93	93
Rac1/GTP	-0.057	0.19	-10000	0	-0.37	114	114
PTPRM	-0.027	0.094	-10000	0	-0.18	117	117
E-cadherin/beta catenin/alpha catenin	0.063	0.085	-10000	0	-0.13	50	50
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.04	0.007	-10000	0	0	18	18

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	0.006	0.084	-10000	0	-0.12	127	127
alphaM/beta2 Integrin/GPIbA	0.051	0.067	-10000	0	-0.11	57	57
alphaM/beta2 Integrin/proMMP-9	0.029	0.081	-10000	0	-0.13	83	83
PLAUR	0.035	0.015	-10000	0	0	82	82
HMGB1	0.041	0.015	-10000	0	-0.053	9	9
alphaM/beta2 Integrin/Talin	0.047	0.075	-10000	0	-0.12	75	75
AGER	0.041	0.015	-10000	0	-0.053	9	9
RAP1A	0.039	0.01	-10000	0	0	35	35
SELPLG	0.039	0.009	-10000	0	0	25	25
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.081	0.08	-10000	0	-0.17	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.028	0.019	-10000	0	0	169	169
CYR61	0.03	0.018	-10000	0	0	149	149
TLN1	0.038	0.011	-10000	0	0	39	39
Rap1/GTP	-0.063	0.17	-10000	0	-0.31	134	134
RHOA	0.04	0.006	-10000	0	0	13	13
P-selectin oligomer	0.039	0.01	-10000	0	0	34	34
MYH2	-0.08	0.17	0.2	2	-0.33	133	135
MST1R	0.038	0.011	-10000	0	0	39	39
leukocyte activation during inflammatory response	0.055	0.063	-10000	0	-0.099	47	47
APOB	0.04	0.007	-10000	0	0	14	14
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.021	0.021	-10000	0	0	265	265
JAM3	0.038	0.012	-10000	0	0	47	47
GP1BA	0.038	0.011	-10000	0	0	42	42
alphaM/beta2 Integrin/CTGF	0.035	0.079	-10000	0	-0.12	93	93
alphaM/beta2 Integrin	-0.066	0.17	-10000	0	-0.35	116	116
JAM3 homodimer	0.038	0.012	-10000	0	0	47	47
ICAM2	0.038	0.01	-10000	0	0	36	36
ICAM1	0.026	0.02	-10000	0	0	206	206
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.065	0.17	-10000	0	-0.34	118	118
cell adhesion	0.051	0.067	-10000	0	-0.11	57	57
NFKB1	0.021	0.069	0.3	1	-0.22	20	21
THY1	0.025	0.02	-10000	0	0	216	216
RhoA/GDP	0.029	0.014	-10000	0	-0.12	4	4
Lipoprotein(a)	0.047	0.02	-10000	0	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	0.024	0.099	-10000	0	-0.13	134	134
IL6	-0.019	0.072	0.3	1	-0.4	10	11
ITGB2	0.034	0.021	-10000	0	-0.051	8	8
elevation of cytosolic calcium ion concentration	0.029	0.1	-10000	0	-0.16	98	98
alphaM/beta2 Integrin/JAM2/JAM3	0.067	0.073	-10000	0	-0.11	52	52
JAM2	0.037	0.012	-10000	0	0	52	52
alphaM/beta2 Integrin/ICAM1	0.05	0.099	-10000	0	-0.14	84	84
alphaM/beta2 Integrin/uPA/Plg	0.038	0.096	-10000	0	-0.14	100	100
RhoA/GTP	-0.085	0.18	-10000	0	-0.34	140	140
positive regulation of phagocytosis	-0.046	0.15	0.2	2	-0.3	103	105
Ron/MSP	0.054	0.028	-10000	0	-0.13	8	8
alphaM/beta2 Integrin/uPAR/uPA	0.032	0.1	-10000	0	-0.16	98	98
alphaM/beta2 Integrin/uPAR	0.043	0.079	-10000	0	-0.14	63	63
PLAU	0.025	0.02	-10000	0	0	210	210
PLAT	0.026	0.02	-10000	0	0	205	205
actin filament polymerization	-0.076	0.16	0.19	2	-0.32	133	135
MST1	0.04	0.007	-10000	0	0	15	15
alphaM/beta2 Integrin/lipoprotein(a)	0.061	0.067	-10000	0	-0.1	47	47
TNF	-0.01	0.07	0.29	1	-0.34	7	8
RAP1B	0.037	0.012	-10000	0	0	54	54
alphaM/beta2 Integrin/uPA	0.017	0.092	-10000	0	-0.15	102	102
fibrinolysis	0.036	0.094	-10000	0	-0.14	100	100
HCK	0.036	0.013	-10000	0	0	65	65
dendritic cell antigen processing and presentation	-0.065	0.17	-10000	0	-0.34	118	118
VTN	0.039	0.008	-10000	0	0	24	24
alphaM/beta2 Integrin/CYR61	0.024	0.083	-10000	0	-0.12	112	112
LPA	0.035	0.014	-10000	0	0	77	77
LRP1	0.036	0.014	-10000	0	0	69	69
cell migration	0.015	0.092	0.18	10	-0.13	129	139
FN1	0.021	0.021	-10000	0	0	268	268
alphaM/beta2 Integrin/Thy1	0.008	0.091	-10000	0	-0.12	150	150
MPO	0.04	0.007	-10000	0	0	14	14
KNG1	0.034	0.016	-10000	0	0	100	100
RAP1/GDP	0.038	0.05	-10000	0	-0.12	43	43
ROCK1	-0.082	0.17	0.22	3	-0.33	136	139
ELA2	0.036	0.013	-10000	0	0	66	66
PLG	0.038	0.011	-10000	0	0	41	41
CTGF	0.034	0.016	-10000	0	0	101	101
alphaM/beta2 Integrin/Hck	0.05	0.071	-10000	0	-0.13	52	52
ITGAM	0.041	0.015	-10000	0	-0.053	9	9
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.071	0.074	-10000	0	-0.12	51	51
HP	0.01	0.018	-10000	0	0	416	416
leukocyte adhesion	0.017	0.1	-10000	0	-0.18	49	49
SELP	0.039	0.01	-10000	0	0	34	34

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.017	0.035	-10000	0	-0.054	75	75
PDGF/PDGFRA/CRKL	0.013	0.069	-10000	0	-0.13	78	78
positive regulation of JUN kinase activity	0.047	0.081	-10000	0	-0.12	92	92
CRKL	0.038	0.01	-10000	0	0	36	36
PDGF/PDGFRA/Caveolin-3	0.011	0.072	-10000	0	-0.13	88	88
AP1	-0.13	0.25	-10000	0	-0.65	96	96
mol:IP3	-0.018	0.042	0.051	26	-0.098	78	104
PLCG1	-0.018	0.042	0.049	25	-0.098	78	103
PDGF/PDGFRA/alphaV Integrin	-0.008	0.09	-10000	0	-0.16	125	125
RAPGEF1	0.039	0.009	-10000	0	0	26	26
CRK	0.038	0.012	-10000	0	0	49	49
mol:Ca2+	-0.018	0.042	0.051	26	-0.098	78	104
CAV3	0.04	0.008	-10000	0	0	19	19
CAV1	0.036	0.014	-10000	0	0	75	75
SHC/Grb2/SOS1	0.049	0.083	-10000	0	-0.12	92	92
PDGF/PDGFRA/Shf	0.012	0.07	-10000	0	-0.13	81	81
FOS	-0.12	0.25	0.29	4	-0.64	96	100
JUN	-0.031	0.037	0.18	3	-0.2	3	6
oligodendrocyte development	-0.008	0.09	-10000	0	-0.16	125	125
GRB2	0.04	0.008	-10000	0	0	21	21
PIK3R1	0.034	0.016	-10000	0	0	99	99
mol:DAG	-0.018	0.042	0.051	26	-0.098	78	104
PDGF/PDGFRA	0.017	0.035	-10000	0	-0.054	75	75
actin cytoskeleton reorganization	0.013	0.071	-10000	0	-0.13	85	85
SRF	-0.007	0.023	0.032	124	-10000	0	124
SHC1	0.039	0.008	-10000	0	0	23	23
PI3K	0.009	0.079	-10000	0	-0.14	92	92
PDGF/PDGFRA/Crk/C3G	0.033	0.071	-10000	0	-0.11	85	85
JAK1	-0.011	0.02	0.027	36	-10000	0	36
ELK1/SRF	-0.025	0.066	0.15	24	-0.15	62	86
SHB	0.04	0.006	-10000	0	0	11	11
SHF	0.039	0.01	-10000	0	0	32	32
CSNK2A1	0.036	0.03	0.084	1	-0.028	59	60
GO:0007205	-0.02	0.053	0.075	7	-0.11	87	94
SOS1	0.037	0.012	-10000	0	0	51	51
Ras protein signal transduction	0.047	0.081	-10000	0	-0.12	92	92
PDGF/PDGFRA/SHB	0.013	0.072	-10000	0	-0.13	85	85
PDGF/PDGFRA/Caveolin-1	0.01	0.074	-10000	0	-0.11	120	120
ITGAV	0.033	0.017	-10000	0	0	110	110
ELK1	-0.031	0.073	0.15	9	-0.18	69	78
PIK3CA	0.029	0.019	-10000	0	0	166	166
PDGF/PDGFRA/Crk	0.012	0.07	-10000	0	-0.1	121	121
JAK-STAT cascade	-0.011	0.02	0.027	36	-10000	0	36
cell proliferation	0.012	0.07	-10000	0	-0.13	81	81

×

TCGA08_retinoblastoma

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
CDKN2B	0.029	0.026	-10000	0	-0.045	39	39
CDKN2C	0.03	0.027	-10000	0	-0.043	46	46
CDKN2A	0.021	0.029	-10000	0	-0.038	60	60
CCND2	0.009	0.045	0.11	79	-0.12	3	82
RB1	-0.012	0.061	0.18	7	-0.14	83	90
CDK4	0.011	0.055	0.13	80	-0.12	17	97
CDK6	0.005	0.064	0.13	81	-0.14	20	101
G1/S progression	0.019	0.068	0.14	103	-0.19	8	111

×

Thromboxane A2 receptor signaling

Figure S15. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S15. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.033	0.016	-10000	0	0	105	105
GNB1/GNG2	-0.063	0.086	-10000	0	-0.18	185	185
AKT1	-0.026	0.14	0.25	3	-0.23	82	85
EGF	0.038	0.01	-10000	0	0	38	38
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.003	0.058	0.19	12	-0.16	3	15
mol:Ca2+	-0.054	0.19	0.31	2	-0.29	192	194
LYN	-0.001	0.055	0.19	11	-0.16	6	17
RhoA/GTP	-0.021	0.087	0.14	7	-0.13	178	185
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.074	0.2	0.3	2	-0.34	188	190
GNG2	0.039	0.009	-10000	0	0	29	29
ARRB2	0.038	0.011	-10000	0	0	46	46
TP alpha/Gq family/GDP/G beta5/gamma2	-0.027	0.16	-10000	0	-0.51	50	50
G beta5/gamma2	-0.073	0.12	-10000	0	-0.24	185	185
PRKCH	-0.074	0.22	0.31	2	-0.35	186	188
DNM1	0.039	0.01	-10000	0	0	33	33
TXA2/TP beta/beta Arrestin3	0.029	0.022	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	0.041	0.005	-10000	0	0	8	8
G12 family/GTP	-0.068	0.18	-10000	0	-0.3	187	187
ADRBK1	0.041	0.004	-10000	0	0	6	6
ADRBK2	0.035	0.015	-10000	0	0	84	84
RhoA/GTP/ROCK1	0.05	0.024	-10000	0	-0.11	9	9
mol:GDP	0.035	0.16	0.45	47	-0.25	2	49
mol:NADP	0.038	0.01	-10000	0	0	35	35
RAB11A	0.04	0.008	-10000	0	0	19	19
PRKG1	0.039	0.009	-10000	0	0	30	30
mol:IP3	-0.077	0.23	0.33	2	-0.37	192	194
cell morphogenesis	0.05	0.023	-10000	0	-0.11	9	9
PLCB2	-0.12	0.3	-10000	0	-0.5	191	191
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.002	0.053	0.19	12	-0.17	2	14
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0	0.056	0.18	12	-0.16	5	17
RHOA	0.04	0.006	-10000	0	0	13	13
PTGIR	0.039	0.009	-10000	0	0	26	26
PRKCB1	-0.08	0.23	0.33	1	-0.38	187	188
GNAQ	0.038	0.012	-10000	0	0	48	48
mol:L-citrulline	0.038	0.01	-10000	0	0	35	35
TXA2/TXA2-R family	-0.12	0.3	0.37	1	-0.52	187	188
LCK	0.003	0.058	0.19	12	-0.16	3	15
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.051	0.047	0.19	4	-0.15	7	11
TXA2-R family/G12 family/GDP/G beta/gamma	0.001	0.13	-10000	0	-0.41	46	46
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.047	0.047	0.19	4	-0.15	7	11
MAPK14	-0.044	0.14	0.28	4	-0.23	184	188
TGM2/GTP	-0.09	0.25	0.39	1	-0.4	184	185
MAPK11	-0.049	0.14	0.24	3	-0.22	185	188
ARHGEF1	-0.031	0.12	0.19	7	-0.18	180	187
GNAI2	0.04	0.006	-10000	0	0	13	13
JNK cascade	-0.08	0.23	0.33	2	-0.38	187	189
RAB11/GDP	0.04	0.008	-10000	0	0	19	19
ICAM1	-0.06	0.2	0.27	8	-0.32	179	187
cAMP biosynthetic process	-0.073	0.21	0.31	2	-0.34	191	193
Gq family/GTP/EBP50	0.01	0.049	0.25	2	-0.14	43	45
actin cytoskeleton reorganization	0.05	0.023	-10000	0	-0.11	9	9
SRC	0.001	0.056	0.18	12	-0.16	3	15
GNB5	0.039	0.008	-10000	0	0	23	23
GNB1	0.039	0.01	-10000	0	0	33	33
EGF/EGFR	0.001	0.076	0.22	11	-0.18	22	33
VCAM1	-0.064	0.21	0.27	7	-0.33	186	193
TP beta/Gq family/GDP/G beta5/gamma2	-0.027	0.16	-10000	0	-0.51	50	50
platelet activation	-0.059	0.19	0.37	2	-0.3	187	189
PGI2/IP	0.028	0.014	-10000	0	-0.12	4	4
PRKACA	0.019	0.022	-10000	0	-0.16	6	6
Gq family/GDP/G beta5/gamma2	-0.018	0.13	-10000	0	-0.41	46	46
TXA2/TP beta/beta Arrestin2	0.012	0.061	-10000	0	-0.31	13	13
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.002	0.021	-10000	0	-0.15	6	6
mol:DAG	-0.091	0.26	0.36	1	-0.42	187	188
EGFR	0.036	0.014	-10000	0	0	67	67
TXA2/TP alpha	-0.11	0.28	0.38	1	-0.46	190	191
Gq family/GTP	-0.011	0.066	-10000	0	-0.18	67	67
YES1	0.001	0.056	0.19	12	-0.16	4	16
GNAI2/GTP	0.025	0.046	-10000	0	-0.11	22	22
PGD2/DP	0.03	0.004	-10000	0	-10000	0	0
SLC9A3R1	0.038	0.012	-10000	0	0	49	49
FYN	0	0.055	0.19	12	-0.16	8	20
mol:NO	0.038	0.01	-10000	0	0	35	35
GNA15	0.036	0.014	-10000	0	0	68	68
PGK/cGMP	0.049	0.018	-10000	0	-10000	0	0
RhoA/GDP	0.04	0.007	-10000	0	0	13	13
TP alpha/TGM2/GDP/G beta/gamma	0.057	0.06	0.26	1	-0.18	7	8
NOS3	0.039	0.01	-10000	0	0	35	35
RAC1	0.039	0.009	-10000	0	0	28	28
PRKCA	-0.075	0.22	0.32	3	-0.35	186	189
PRKCB	-0.072	0.22	0.29	2	-0.35	186	188
PRKCE	-0.075	0.22	0.32	4	-0.36	183	187
PRKCD	-0.082	0.23	0.33	1	-0.38	184	185
PRKCG	-0.081	0.23	0.33	2	-0.38	183	185
muscle contraction	-0.11	0.28	0.37	1	-0.48	187	188
PRKCZ	-0.071	0.21	0.3	2	-0.34	184	186
ARR3	0.041	0.002	-10000	0	0	1	1
TXA2/TP beta	0.045	0.051	0.23	2	-0.13	10	12
PRKCQ	-0.075	0.22	0.34	2	-0.36	180	182
MAPKKK cascade	-0.1	0.26	0.35	1	-0.44	188	189
SELE	-0.053	0.18	0.27	4	-0.29	187	191
TP beta/GNAI2/GDP/G beta/gamma	0.069	0.057	0.25	2	-0.16	8	10
ROCK1	0.04	0.008	-10000	0	0	21	21
GNA14	0.039	0.009	-10000	0	0	29	29
chemotaxis	-0.15	0.34	-10000	0	-0.6	187	187
GNA12	0.039	0.01	-10000	0	0	33	33
GNA13	0.039	0.008	-10000	0	0	23	23
GNA11	0.037	0.013	-10000	0	0	61	61
Rac1/GTP	0.028	0.009	-10000	0	-0.12	1	1

×

TRAIL signaling pathway

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
TNFSF10	0.021	0.021	-10000	0	0	265	265
positive regulation of NF-kappaB transcription factor activity	0.005	0.065	-10000	0	-0.13	89	89
MAP2K4	-0.008	0.088	0.18	3	-0.27	31	34
IKBKB	0.038	0.011	-10000	0	0	41	41
TNFRSF10B	0.033	0.017	-10000	0	0	111	111
TNFRSF10A	0.032	0.017	-10000	0	0	125	125
SMPD1	-0.007	0.043	-10000	0	-0.1	88	88
IKBKG	0.041	0.002	-10000	0	0	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.032	0.017	-10000	0	0	122	122
TRAIL/TRAILR2	0.005	0.066	-10000	0	-0.13	91	91
TRAIL/TRAILR3	0.004	0.066	-10000	0	-0.13	93	93
TRAIL/TRAILR1	0.003	0.067	-10000	0	-0.13	93	93
TRAIL/TRAILR4	0.005	0.065	-10000	0	-0.13	89	89
TRAIL/TRAILR1/DAP3/GTP	0.013	0.064	-10000	0	-0.1	92	92
IKK complex	0.022	0.088	-10000	0	-0.28	29	29
RIPK1	0.039	0.01	-10000	0	0	32	32
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.026	0.021	-10000	0	-0.12	9	9
MAPK3	-0.01	0.01	-10000	0	-10000	0	0
MAP3K1	-0.005	0.096	-10000	0	-0.29	33	33
TRAILR4 (trimer)	0.032	0.017	-10000	0	0	122	122
TRADD	0.037	0.013	-10000	0	0	61	61
TRAILR1 (trimer)	0.032	0.017	-10000	0	0	125	125
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.017	0.08	-10000	0	-0.17	88	88
CFLAR	0.04	0.008	-10000	0	0	19	19
MAPK1	-0.01	0.01	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP	0.032	0.082	-10000	0	-0.11	79	79
mol:ceramide	-0.007	0.043	-10000	0	-0.099	88	88
FADD	0.04	0.008	-10000	0	0	20	20
MAPK8	-0.02	0.097	0.2	3	-0.26	47	50
TRAF2	0.039	0.01	-10000	0	0	32	32
TRAILR3 (trimer)	0.032	0.017	-10000	0	0	119	119
CHUK	0.038	0.011	-10000	0	0	46	46
TRAIL/TRAILR1/FADD	0.014	0.069	-10000	0	-0.11	89	89
DAP3	0.038	0.011	-10000	0	0	40	40
CASP10	-0.006	0.1	0.16	81	-0.2	76	157
JNK cascade	0.005	0.065	-10000	0	-0.13	89	89
TRAIL (trimer)	0.021	0.021	-10000	0	0	265	265
TNFRSF10C	0.032	0.017	-10000	0	0	119	119
TRAIL/TRAILR1/DAP3/GTP/FADD	0.023	0.071	-10000	0	-0.1	87	87
TRAIL/TRAILR2/FADD	0.017	0.068	-10000	0	-0.11	88	88
cell death	-0.007	0.043	-10000	0	-0.099	88	88
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.017	0.081	-10000	0	-0.18	85	85
TRAILR2 (trimer)	0.033	0.017	-10000	0	0	111	111
CASP8	-0.005	0.12	-10000	0	-0.61	16	16
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.033	0.082	-10000	0	-0.11	76	76

×

BARD1 signaling events

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
BARD1/CSTF1	0.039	0.053	-10000	0	-0.14	38	38
ATM	0.036	0.014	-10000	0	0	69	69
UBE2D3	0.039	0.009	-10000	0	0	30	30
PRKDC	0.038	0.011	-10000	0	0	44	44
ATR	0.035	0.015	-10000	0	0	84	84
UBE2L3	0.039	0.01	-10000	0	0	34	34
FANCD2	-0.005	0.09	-10000	0	-0.25	58	58
protein ubiquitination	0.01	0.098	-10000	0	-0.13	147	147
XRCC5	0.038	0.011	-10000	0	0	41	41
XRCC6	0.036	0.014	-10000	0	0	69	69
M/R/N Complex	0.048	0.071	-10000	0	-0.15	50	50
MRE11A	0.038	0.012	-10000	0	0	49	49
DNA-PK	0.051	0.067	-10000	0	-0.14	47	47
FA complex/FANCD2/Ubiquitin	-0.002	0.12	-10000	0	-0.38	34	34
FANCF	0.04	0.007	-10000	0	0	18	18
BRCA1	0.034	0.015	-10000	0	0	93	93
CCNE1	0.026	0.02	-10000	0	0	202	202
CDK2/Cyclin E1	0.009	0.074	-10000	0	-0.14	97	97
FANCG	0.04	0.007	-10000	0	0	14	14
BRCA1/BACH1/BARD1	0.027	0.068	-10000	0	-0.14	72	72
FANCE	0.04	0.006	-10000	0	0	12	12
FANCC	0.039	0.009	-10000	0	0	25	25
NBN	0.035	0.015	-10000	0	0	87	87
FANCA	0.034	0.016	-10000	0	0	94	94
DNA repair	-0.017	0.13	0.26	21	-0.34	43	64
BRCA1/BARD1/ubiquitin	0.027	0.068	-10000	0	-0.14	72	72
BARD1/DNA-PK	0.06	0.083	-10000	0	-0.14	60	60
FANCL	0.037	0.012	-10000	0	0	52	52
mRNA polyadenylation	-0.039	0.052	0.14	38	-10000	0	38
BRCA1/BARD1/CTIP/M/R/N Complex	-0.024	0.14	0.16	2	-0.28	80	82
BRCA1/BACH1/BARD1/TopBP1	0.038	0.077	-10000	0	-0.13	80	80
BRCA1/BARD1/P53	0.004	0.1	-10000	0	-0.13	182	182
BARD1/CSTF1/BRCA1	0.039	0.072	-10000	0	-0.12	73	73
BRCA1/BACH1	0.034	0.015	-10000	0	0	93	93
BARD1	0.036	0.013	-10000	0	0	64	64
PCNA	0.034	0.015	-10000	0	0	89	89
BRCA1/BARD1/UbcH5C	0.043	0.071	-10000	0	-0.12	73	73
BRCA1/BARD1/UbcH7	0.043	0.07	-10000	0	-0.12	70	70
BRCA1/BARD1/RAD51/PCNA	0.035	0.095	-10000	0	-0.13	115	115
BARD1/DNA-PK/P53	0.02	0.11	-10000	0	-0.13	170	170
BRCA1/BARD1/Ubiquitin	0.027	0.068	-10000	0	-0.14	72	72
BRCA1/BARD1/CTIP	0.015	0.087	0.18	13	-0.13	116	129
FA complex	0.009	0.086	-10000	0	-0.26	34	34
BARD1/EWS	0.041	0.049	-10000	0	-0.13	34	34
RBBP8	-0.015	0.009	-10000	0	-10000	0	0
TP53	0.026	0.02	-10000	0	0	207	207
TOPBP1	0.037	0.012	-10000	0	0	50	50
G1/S transition of mitotic cell cycle	-0.003	0.1	0.12	182	-10000	0	182
BRCA1/BARD1	0.014	0.1	-10000	0	-0.13	147	147
CSTF1	0.037	0.013	-10000	0	0	57	57
BARD1/EWS-Fli1	0.019	0.037	-10000	0	-0.12	33	33
CDK2	0.037	0.013	-10000	0	0	56	56
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.035	0.015	-10000	0	0	83	83
RAD50	0.039	0.01	-10000	0	0	35	35
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.027	0.068	-10000	0	-0.14	72	72
EWSR1	0.038	0.012	-10000	0	0	48	48

×

TCGA08_rtk_signaling

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
PDGFRA	0.029	0.019	-10000	0	0	161	161
HRAS	0.039	0.01	-10000	0	0	31	31
EGFR	0.036	0.014	-10000	0	0	67	67
AKT	0.02	0.091	0.21	13	-0.19	35	48
FOXO3	0	0	-10000	0	-10000	0	0
AKT1	0.039	0.01	-10000	0	0	34	34
FOXO1	0	0	-10000	0	-10000	0	0
AKT3	0.03	0.018	-10000	0	0	151	151
FOXO4	0	0	-10000	0	-10000	0	0
MET	0.027	0.02	-10000	0	0	191	191
PIK3CA	0.029	0.019	-10000	0	0	166	166
PIK3CB	0.034	0.016	-10000	0	0	95	95
NRAS	0.039	0.009	-10000	0	0	30	30
PIK3CG	0.033	0.017	-10000	0	0	112	112
PIK3R3	0.034	0.016	-10000	0	0	96	96
PIK3R2	0.036	0.014	-10000	0	0	68	68
NF1	0.034	0.016	-10000	0	0	96	96
RAS	0.002	0.076	0.15	23	-0.23	23	46
ERBB2	0.038	0.012	-10000	0	0	47	47
proliferation/survival/translation	-0.021	0.083	0.21	28	-0.21	18	46
PI3K	0.007	0.087	0.17	25	-0.22	39	64
PIK3R1	0.034	0.016	-10000	0	0	99	99
KRAS	0.034	0.016	-10000	0	0	95	95
FOXO	0.039	0.053	0.17	24	-10000	0	24
AKT2	0.037	0.012	-10000	0	0	54	54
PTEN	0.038	0.01	-10000	0	0	36	36

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.038	0.01	-10000	0	0	36	36
Rac1/GDP	0.032	0.025	-10000	0	-0.024	67	67
DOCK1	0.037	0.012	-10000	0	0	53	53
ITGA4	0.035	0.015	-10000	0	0	88	88
RAC1	0.039	0.009	-10000	0	0	28	28
alpha4/beta7 Integrin	0.031	0.065	-10000	0	-0.14	66	66
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.038	0.012	-10000	0	0	49	49
alpha4/beta1 Integrin	0.045	0.063	-10000	0	-0.12	53	53
alpha4/beta7 Integrin/Paxillin	0.051	0.07	0.18	56	-0.11	53	109
lamellipodium assembly	-0.025	0.14	-10000	0	-0.36	65	65
PIK3CA	0.029	0.019	-10000	0	0	166	166
PI3K	0.023	0.06	-10000	0	-0.15	44	44
ARF6	0.04	0.007	-10000	0	0	16	16
TLN1	0.038	0.011	-10000	0	0	39	39
PXN	-0.017	0.008	-10000	0	-10000	0	0
PIK3R1	0.034	0.016	-10000	0	0	99	99
ARF6/GTP	0.061	0.071	-10000	0	-0.11	54	54
cell adhesion	0.06	0.079	0.19	50	-0.11	65	115
CRKL/CBL	0.055	0.02	-10000	0	-0.13	1	1
alpha4/beta1 Integrin/Paxillin	0.05	0.068	0.18	52	-0.11	52	104
ITGB1	0.038	0.01	-10000	0	0	36	36
ITGB7	0.038	0.01	-10000	0	0	38	38
ARF6/GDP	0.033	0.025	-10000	0	-0.024	66	66
alpha4/beta1 Integrin/Paxillin/VCAM1	0.021	0.095	0.2	29	-0.13	121	150
p130Cas/Crk/Dock1	0.056	0.052	-10000	0	-0.12	27	27
VCAM1	0.02	0.021	-10000	0	0	281	281
alpha4/beta1 Integrin/Paxillin/Talin	0.062	0.08	0.2	50	-0.11	65	115
alpha4/beta1 Integrin/Paxillin/GIT1	0.067	0.073	0.2	48	-0.11	52	100
BCAR1	0.036	0.013	-10000	0	0	65	65
mol:GDP	-0.065	0.072	0.11	52	-0.19	48	100
CBL	0.04	0.008	-10000	0	0	20	20
PRKACA	0.035	0.015	-10000	0	0	84	84
GIT1	0.039	0.009	-10000	0	0	25	25
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.062	0.08	0.2	50	-0.11	65	115
Rac1/GTP	-0.03	0.16	-10000	0	-0.4	65	65

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.007	0.005	0	182	-10000	0	182
GNB1/GNG2	0.039	0.068	-10000	0	-0.11	83	83
regulation of S phase of mitotic cell cycle	-0.011	0.075	-10000	0	-0.17	83	83
GNAO1	0.035	0.015	-10000	0	0	85	85
HRAS	0.039	0.01	-10000	0	0	31	31
SHBG/T-DHT	0.026	0.007	-10000	0	-10000	0	0
PELP1	0.038	0.011	-10000	0	0	39	39
AKT1	-0.009	0.003	0.002	41	-10000	0	41
MAP2K1	-0.034	0.078	0.17	23	-0.17	77	100
T-DHT/AR	0.006	0.053	-10000	0	-0.12	75	75
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.007	100	100
GNAI2	0.04	0.006	-10000	0	0	13	13
GNAI3	0.038	0.011	-10000	0	0	45	45
GNAI1	0.034	0.015	-10000	0	0	93	93
mol:GDP	-0.039	0.085	-10000	0	-0.25	66	66
cell proliferation	-0.069	0.17	0.24	7	-0.4	103	110
PIK3CA	0.029	0.019	-10000	0	0	166	166
FOS	-0.12	0.29	0.28	2	-0.7	103	105
mol:Ca2+	-0.007	0.021	-10000	0	-0.048	83	83
MAPK3	-0.052	0.13	0.23	7	-0.3	94	101
MAPK1	-0.038	0.13	-10000	0	-0.42	33	33
PIK3R1	0.034	0.016	-10000	0	0	99	99
mol:IP3	0	0.002	0.002	12	-0.004	100	112
cAMP biosynthetic process	-0.001	0.024	0.2	4	-10000	0	4
GNG2	0.039	0.009	-10000	0	0	29	29
potassium channel inhibitor activity	0	0.002	0.002	12	-0.004	100	112
HRAS/GTP	0.025	0.076	-10000	0	-0.09	137	137
actin cytoskeleton reorganization	0.027	0.05	-10000	0	-0.11	43	43
SRC	0.039	0.009	-10000	0	0	28	28
voltage-gated calcium channel activity	0	0.002	0.002	12	-0.004	100	112
PI3K	0.022	0.051	-10000	0	-0.12	44	44
apoptosis	0.059	0.18	0.39	110	-0.23	3	113
T-DHT/AR/PELP1	0.025	0.056	-10000	0	-0.11	75	75
HRAS/GDP	-0.002	0.11	0.15	1	-0.24	67	68
CREB1	-0.074	0.18	0.25	1	-0.42	110	111
RAC1-CDC42/GTP	0.037	0.057	-10000	0	-0.11	43	43
AR	0.032	0.017	-10000	0	0	118	118
GNB1	0.039	0.01	-10000	0	0	33	33
RAF1	-0.021	0.074	0.18	24	-0.18	15	39
RAC1-CDC42/GDP	0.02	0.11	-10000	0	-0.24	65	65
T-DHT/AR/PELP1/Src	0.039	0.064	-10000	0	-0.1	72	72
MAP2K2	-0.028	0.074	0.17	22	-0.17	64	86
T-DHT/AR/PELP1/Src/PI3K	-0.011	0.075	-10000	0	-0.17	83	83
GNAZ	0.038	0.011	-10000	0	0	46	46
SHBG	0.038	0.01	-10000	0	0	37	37
Gi family/GNB1/GNG2/GDP	-0.007	0.11	-10000	0	-0.31	36	36
mol:T-DHT	0	0.001	-10000	0	-0.003	25	25
RAC1	0.039	0.009	-10000	0	0	28	28
GNRH1	-0.008	0.004	0	107	-10000	0	107
Gi family/GTP	-0.019	0.077	-10000	0	-0.18	73	73
CDC42	0.04	0.007	-10000	0	0	18	18

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.066	0.18	-10000	0	-0.39	122	122
IHH	0.021	0.066	-10000	0	-0.098	126	126
SHH Np/Cholesterol/GAS1	0.027	0.025	-10000	0	-0.1	12	12
LRPAP1	0.036	0.014	-10000	0	0	72	72
dorsoventral neural tube patterning	-0.027	0.025	0.1	12	-10000	0	12
SMO/beta Arrestin2	0.015	0.12	0.24	2	-0.2	104	106
SMO	-0.004	0.11	-10000	0	-0.2	109	109
AKT1	-0.015	0.13	-10000	0	-0.4	35	35
ARRB2	0.038	0.011	-10000	0	0	46	46
BOC	0.035	0.015	-10000	0	0	82	82
ADRBK1	0.041	0.004	-10000	0	0	6	6
heart looping	-0.003	0.11	-10000	0	-0.2	109	109
STIL	-0.002	0.096	0.21	26	-0.17	104	130
DHH N/PTCH2	0.058	0.014	-10000	0	-10000	0	0
DHH N/PTCH1	0.002	0.11	-10000	0	-0.19	125	125
PIK3CA	0.029	0.019	-10000	0	0	166	166
DHH	0.04	0.006	-10000	0	0	11	11
PTHLH	-0.057	0.16	-10000	0	-0.38	108	108
determination of left/right symmetry	-0.003	0.11	-10000	0	-0.2	109	109
PIK3R1	0.034	0.016	-10000	0	0	99	99
skeletal system development	-0.056	0.16	-10000	0	-0.37	108	108
IHH N/Hhip	0.034	0.054	-10000	0	-0.15	1	1
DHH N/Hhip	0.055	0.02	-10000	0	-0.13	1	1
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.003	0.11	-10000	0	-0.2	109	109
pancreas development	0.038	0.011	-10000	0	0	44	44
HHAT	0.039	0.009	-10000	0	0	25	25
PI3K	0.023	0.06	-10000	0	-0.15	44	44
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.036	0.013	-10000	0	0	66	66
somite specification	-0.003	0.11	-10000	0	-0.2	109	109
SHH Np/Cholesterol/PTCH1	-0.007	0.085	-10000	0	-0.17	109	109
SHH Np/Cholesterol/PTCH2	0.032	0.015	-10000	0	-0.1	1	1
SHH Np/Cholesterol/Megalin	0.021	0.028	-10000	0	-0.1	15	15
SHH	-0.018	0.007	-10000	0	-10000	0	0
catabolic process	-0.037	0.095	-10000	0	-0.21	126	126
SMO/Vitamin D3	-0.007	0.1	0.2	17	-0.2	106	123
SHH Np/Cholesterol/Hhip	0.031	0.017	-10000	0	-0.1	2	2
LRP2	0.029	0.019	-10000	0	0	160	160
receptor-mediated endocytosis	0	0.1	0.19	18	-0.18	102	120
SHH Np/Cholesterol/BOC	0.026	0.027	-10000	0	-0.1	16	16
SHH Np/Cholesterol/CDO	0.023	0.033	-10000	0	-0.1	27	27
mesenchymal cell differentiation	-0.03	0.017	0.1	2	-10000	0	2
mol:Vitamin D3	-0.015	0.086	0.2	20	-0.17	108	128
IHH N/PTCH2	0.037	0.054	-10000	0	-0.059	121	121
CDON	0.034	0.015	-10000	0	0	91	91
IHH N/PTCH1	-0.021	0.11	-10000	0	-0.21	126	126
Megalin/LRPAP1	0.027	0.054	-10000	0	-0.14	40	40
PTCH2	0.04	0.008	-10000	0	0	19	19
SHH Np/Cholesterol	0.031	0.041	0.2	31	-0.097	1	32
PTCH1	-0.037	0.096	-10000	0	-0.21	126	126
HHIP	0.038	0.011	-10000	0	0	44	44

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.028	0.013	-10000	0	-0.12	3	3
alphaV beta3 Integrin	0.029	0.078	-10000	0	-0.12	91	91
PTK2	-0.014	0.13	0.26	5	-0.28	70	75
IGF1R	0.033	0.017	-10000	0	0	112	112
PI4KB	0	0	-10000	0	-10000	0	0
MFGE8	0.031	0.018	-10000	0	0	137	137
SRC	0.039	0.009	-10000	0	0	28	28
CDKN1B	0.003	0.087	-10000	0	-0.33	29	29
VEGFA	0	0	-10000	0	-10000	0	0
ILK	0.016	0.056	-10000	0	-0.27	12	12
ROCK1	0.04	0.008	-10000	0	0	21	21
AKT1	0.007	0.051	0.21	4	-0.26	11	15
PTK2B	-0.014	0.06	0.19	12	-0.18	13	25
alphaV/beta3 Integrin/JAM-A	0.039	0.078	0.2	6	-0.12	85	91
CBL	0.04	0.008	-10000	0	0	20	20
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.031	0.079	-10000	0	-0.13	91	91
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.054	0.083	-10000	0	-0.12	85	85
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.004	0.084	-10000	0	-0.17	94	94
alphaV/beta3 Integrin/Syndecan-1	0.029	0.079	-10000	0	-0.12	94	94
PI4KA	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.018	0.1	-10000	0	-0.14	173	173
PI4 Kinase	0	0	-10000	0	-10000	0	0
PIK3CA	0.029	0.019	-10000	0	0	166	166
alphaV/beta3 Integrin/Osteopontin	0.007	0.098	-10000	0	-0.15	128	128
RPS6KB1	-0.033	0.1	0.27	13	-0.2	58	71
TLN1	0.038	0.011	-10000	0	0	39	39
MAPK3	-0.049	0.15	0.22	3	-0.33	112	115
GPR124	0.037	0.012	-10000	0	0	55	55
MAPK1	-0.048	0.15	0.22	3	-0.34	108	111
PXN	0.04	0.006	-10000	0	0	10	10
PIK3R1	0.034	0.016	-10000	0	0	99	99
alphaV/beta3 Integrin/Tumstatin	0.031	0.079	-10000	0	-0.13	91	91
cell adhesion	-0.003	0.098	-10000	0	-0.16	128	128
ANGPTL3	0.04	0.007	-10000	0	0	15	15
VEGFR2 homodimer/VEGFA homodimer/Src	0.05	0.019	-10000	0	-0.11	2	2
IGF-1R heterotetramer	0.033	0.017	-10000	0	0	112	112
Rac1/GDP	0.029	0.009	-10000	0	-0.12	1	1
TGFBR2	0.039	0.01	-10000	0	0	34	34
ITGB3	0.032	0.017	-10000	0	0	116	116
IGF1	0.035	0.014	-10000	0	0	77	77
RAC1	0.039	0.009	-10000	0	0	28	28
regulation of cell-matrix adhesion	0.03	0.075	-10000	0	-0.12	82	82
apoptosis	0.033	0.016	-10000	0	0	110	110
CD47	0.036	0.013	-10000	0	0	65	65
alphaV/beta3 Integrin/CD47	0.023	0.086	-10000	0	-0.14	99	99
VCL	0.039	0.01	-10000	0	0	34	34
alphaV/beta3 Integrin/Del1	0.007	0.082	-10000	0	-0.13	113	113
CSF1	0.035	0.015	-10000	0	0	84	84
PIK3C2A	-0.004	0.1	-10000	0	-0.34	43	43
PI4 Kinase/Pyk2	0.006	0.055	-10000	0	-0.11	81	81
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.029	0.073	-10000	0	-0.11	94	94
FAK1/Vinculin	0.005	0.12	0.26	6	-0.24	70	76
alphaV beta3/Integrin/ppsTEM5	0.031	0.075	-10000	0	-0.12	82	82
RHOA	0.04	0.006	-10000	0	0	13	13
VTN	0.039	0.008	-10000	0	0	24	24
BCAR1	0.036	0.013	-10000	0	0	65	65
FGF2	0.039	0.01	-10000	0	0	33	33
F11R	-0.019	0.006	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Lactadherin	0.01	0.088	-10000	0	-0.14	123	123
alphaV/beta3 Integrin/TGFBR2	0.027	0.084	-10000	0	-0.14	94	94
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.047	0.089	-10000	0	-0.13	93	93
HSP90AA1	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.026	0.077	-10000	0	-0.12	101	101
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.021	0.021	-10000	0	0	268	268
alphaV/beta3 Integrin/Pyk2	0.018	0.067	0.21	1	-0.11	89	90
SDC1	0.039	0.009	-10000	0	0	25	25
VAV3	-0.031	0.072	0.21	15	-0.21	36	51
PTPN11	0.039	0.009	-10000	0	0	29	29
IRS1	0.04	0.008	-10000	0	0	22	22
FAK1/Paxillin	0.007	0.12	0.26	6	-0.24	71	77
cell migration	-0.004	0.11	0.25	6	-0.22	70	76
ITGAV	0.033	0.017	-10000	0	0	110	110
PI3K	0.026	0.087	-10000	0	-0.14	68	68
SPP1	0.031	0.018	-10000	0	0	139	139
KDR	0.039	0.009	-10000	0	0	27	27
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.033	0.017	-10000	0	0	110	110
COL4A3	0.041	0.005	-10000	0	0	7	7
angiogenesis	-0.053	0.17	0.26	3	-0.37	111	114
Rac1/GTP	-0.033	0.075	0.21	15	-0.2	34	49
EDIL3	0.027	0.02	-10000	0	0	185	185
cell proliferation	0.027	0.083	-10000	0	-0.14	94	94

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.015	0.14	-10000	0	-0.34	29	29
MAP3K8	0.039	0.009	-10000	0	0	24	24
FOS	0.015	0.1	-10000	0	-0.3	21	21
PRKCA	0.026	0.029	-10000	0	-0.015	167	167
PTPN7	0.03	0.032	0.071	1	-0.031	109	110
HRAS	0.039	0.01	-10000	0	0	31	31
PRKCB	0	0.007	0.01	93	-0.013	100	193
NRAS	0.039	0.009	-10000	0	0	30	30
RAS family/GTP	0.053	0.05	-10000	0	-0.11	27	27
MAPK3	0.029	0.078	-10000	0	-0.43	8	8
MAP2K1	0	0.092	0.16	3	-0.27	44	47
ELK1	0.027	0.031	-10000	0	-0.038	101	101
BRAF	-0.002	0.065	-10000	0	-0.28	26	26
mol:GTP	0	0.002	0.002	84	-0.004	100	184
MAPK1	0.015	0.1	-10000	0	-0.38	26	26
RAF1	-0.007	0.074	-10000	0	-0.28	35	35
KRAS	0.034	0.016	-10000	0	0	95	95

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.028	0.019	-10000	0	-0.12	8	8
PRKCZ	0.039	0.009	-10000	0	0	27	27
MAP3K7IP2	0.037	0.012	-10000	0	0	53	53
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.034	0.13	-10000	0	-0.29	95	95
IRAK/TOLLIP	0.038	0.026	0.19	3	-0.1	10	13
IKBKB	0.038	0.011	-10000	0	0	41	41
IKBKG	0.041	0.002	-10000	0	0	2	2
IL1 alpha/IL1R2	0.046	0.038	-10000	0	-0.13	16	16
IL1A	0.039	0.009	-10000	0	0	30	30
IL1B	-0.012	0.01	-10000	0	-10000	0	0
IRAK/TRAF6/p62/Atypical PKCs	0.043	0.076	0.22	2	-0.12	61	63
IL1R2	0.035	0.015	-10000	0	0	80	80
IL1R1	0.031	0.018	-10000	0	0	141	141
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.045	0.14	-10000	0	-0.3	92	92
TOLLIP	0.039	0.01	-10000	0	0	32	32
TICAM2	0.037	0.012	-10000	0	0	51	51
MAP3K3	0.04	0.007	-10000	0	0	14	14
TAK1/TAB1/TAB2	0.061	0.054	-10000	0	-0.14	26	26
IKK complex/ELKS	0.013	0.084	0.28	1	-0.27	25	26
JUN	-0.037	0.056	0.16	16	-0.19	17	33
MAP3K7	0.038	0.01	-10000	0	0	38	38
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0	0.11	-10000	0	-0.17	121	121
IL1 alpha/IL1R1/IL1RAP/MYD88	0.037	0.084	-10000	0	-0.12	91	91
PIK3R1	0.034	0.016	-10000	0	0	99	99
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.038	0.098	-10000	0	-0.13	100	100
IL1 beta fragment/IL1R1/IL1RAP	-0.011	0.096	0.18	6	-0.15	147	153
NFKB1	0.036	0.013	-10000	0	0	66	66
MAPK8	-0.029	0.052	0.17	15	-0.2	16	31
IRAK1	0.016	0.014	0.069	1	-0.11	6	7
IL1RN/IL1R1	0.022	0.07	-10000	0	-0.14	81	81
IRAK4	0.036	0.014	-10000	0	0	68	68
PRKCI	0.027	0.02	-10000	0	0	192	192
TRAF6	0.04	0.008	-10000	0	0	19	19
PI3K	0.023	0.06	-10000	0	-0.15	44	44
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.036	0.14	0.17	1	-0.31	96	97
CHUK	0.038	0.011	-10000	0	0	46	46
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.011	0.096	0.18	6	-0.15	147	153
IL1 beta/IL1R2	-0.004	0.088	0.24	1	-0.15	131	132
IRAK/TRAF6/TAK1/TAB1/TAB2	0.071	0.068	0.22	1	-0.14	32	33
NF kappa B1 p50/RelA	-0.011	0.11	-10000	0	-0.18	116	116
IRAK3	0.034	0.015	-10000	0	0	93	93
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.003	0.12	-10000	0	-0.16	137	137
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.015	0.099	-10000	0	-0.2	97	97
IL1 alpha/IL1R1/IL1RAP	0.017	0.077	-10000	0	-0.13	91	91
RELA	0.04	0.006	-10000	0	0	10	10
MAP3K7IP1	0.037	0.012	-10000	0	0	51	51
SQSTM1	0.038	0.011	-10000	0	0	46	46
MYD88	0.04	0.006	-10000	0	0	12	12
IRAK/TRAF6/MEKK3	0.06	0.036	0.21	3	-0.11	18	21
IL1RAP	0.027	0.02	-10000	0	0	185	185
UBE2N	0.04	0.007	-10000	0	0	16	16
IRAK/TRAF6	-0.022	0.094	-10000	0	-0.16	134	134
CASP1	0.027	0.019	-10000	0	0	184	184
IL1RN/IL1R2	0.041	0.048	-10000	0	-0.14	30	30
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.002	0.1	0.2	6	-0.15	140	146
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.023	0.13	0.21	1	-0.28	94	95
PIK3CA	0.029	0.019	-10000	0	0	166	166
IL1RN	0.038	0.011	-10000	0	0	39	39
TRAF6/TAK1/TAB1/TAB2	0.072	0.066	-10000	0	-0.14	32	32
MAP2K6	-0.025	0.053	0.19	15	-0.2	13	28

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.17	0.61	-10000	0	-1.2	120	120
IL23A	-0.11	0.55	-10000	0	-1.2	80	80
NF kappa B1 p50/RelA/I kappa B alpha	-0.11	0.54	-10000	0	-1.2	86	86
positive regulation of T cell mediated cytotoxicity	-0.13	0.61	-10000	0	-1.3	89	89
ITGA3	-0.16	0.58	-10000	0	-1.1	115	115
IL17F	-0.041	0.36	0.49	7	-0.7	87	94
IL12B	0.033	0.072	0.16	8	-0.082	2	10
STAT1 (dimer)	-0.15	0.58	-10000	0	-1.3	88	88
CD4	-0.12	0.57	0.66	2	-1.2	96	98
IL23	-0.11	0.52	-10000	0	-1.2	79	79
IL23R	0.037	0.14	-10000	0	-1.2	3	3
IL1B	-0.13	0.59	-10000	0	-1.3	93	93
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.099	0.51	-10000	0	-1.1	80	80
TYK2	0.024	0.055	0.13	2	-10000	0	2
STAT4	0.039	0.008	-10000	0	0	24	24
STAT3	0.038	0.011	-10000	0	0	41	41
IL18RAP	0.041	0.007	-10000	0	0	15	15
IL12RB1	0.023	0.057	0.13	3	-10000	0	3
PIK3CA	0.029	0.019	-10000	0	0	166	166
IL12Rbeta1/TYK2	0.035	0.068	-10000	0	-10000	0	0
IL23R/JAK2	0.047	0.17	-10000	0	-1.2	3	3
positive regulation of chronic inflammatory response	-0.13	0.61	-10000	0	-1.3	89	89
natural killer cell activation	-0.002	0.009	-10000	0	-10000	0	0
JAK2	0.031	0.068	0.16	8	-0.081	3	11
PIK3R1	0.034	0.016	-10000	0	0	99	99
NFKB1	0.038	0.015	-10000	0	0	66	66
RELA	0.042	0.008	-10000	0	0	10	10
positive regulation of dendritic cell antigen processing and presentation	-0.098	0.5	-10000	0	-1.1	79	79
ALOX12B	-0.099	0.51	-10000	0	-1.1	82	82
CXCL1	-0.13	0.57	-10000	0	-1.2	104	104
T cell proliferation	-0.13	0.61	-10000	0	-1.3	89	89
NFKBIA	0.038	0.015	-10000	0	0	64	64
IL17A	-0.025	0.3	0.42	10	-0.54	88	98
PI3K	-0.15	0.53	-10000	0	-1.2	86	86
IFNG	0.007	0.038	0.1	5	-0.1	13	18
STAT3 (dimer)	-0.14	0.5	-10000	0	-1.1	87	87
IL18R1	0.041	0.008	-10000	0	0	19	19
IL23/IL23R/JAK2/TYK2/SOCS3	-0.015	0.34	0.5	4	-0.66	74	78
IL18/IL18R	0.049	0.067	-10000	0	-0.11	61	61
macrophage activation	-0.007	0.021	0.033	1	-0.045	74	75
TNF	-0.11	0.54	-10000	0	-1.2	80	80
STAT3/STAT4	-0.12	0.56	-10000	0	-1.2	87	87
STAT4 (dimer)	-0.13	0.58	-10000	0	-1.3	87	87
IL18	0.031	0.019	-10000	0	0	148	148
IL19	-0.099	0.51	-10000	0	-1.1	81	81
STAT5A (dimer)	-0.13	0.58	-10000	0	-1.3	88	88
STAT1	0.034	0.016	-10000	0	0	102	102
SOCS3	0.036	0.013	-10000	0	0	63	63
CXCL9	-0.16	0.61	-10000	0	-1.2	120	120
MPO	-0.099	0.51	-10000	0	-1.1	82	82
positive regulation of humoral immune response	-0.13	0.61	-10000	0	-1.3	89	89
IL23/IL23R/JAK2/TYK2	-0.17	0.65	-10000	0	-1.4	89	89
IL6	-0.1	0.53	-10000	0	-1.2	84	84
STAT5A	0.038	0.01	-10000	0	0	36	36
IL2	0.039	0.016	-10000	0	-0.032	12	12
positive regulation of tyrosine phosphorylation of STAT protein	-0.002	0.009	-10000	0	-10000	0	0
CD3E	-0.11	0.54	0.68	1	-1.2	87	88
keratinocyte proliferation	-0.13	0.61	-10000	0	-1.3	89	89
NOS2	-0.1	0.51	-10000	0	-1.1	89	89

×

Signaling events mediated by PTP1B

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
PDGFRB	0.036	0.013	-10000	0	0	65	65
Jak2/Leptin Receptor	-0.019	0.15	0.25	1	-0.4	54	55
PTP1B/AKT1	-0.034	0.11	-10000	0	-0.24	87	87
FYN	0.034	0.016	-10000	0	0	94	94
p210 bcr-abl/PTP1B	-0.052	0.11	-10000	0	-0.25	95	95
EGFR	0.036	0.017	-10000	0	-0.004	76	76
EGF/EGFR	-0.025	0.12	-10000	0	-0.23	90	90
CSF1	0.035	0.015	-10000	0	0	84	84
AKT1	0.039	0.01	-10000	0	0	34	34
INSR	0.038	0.012	-10000	0	0	49	49
PTP1B/N-cadherin	-0.054	0.12	-10000	0	-0.24	125	125
Insulin Receptor/Insulin	-0.008	0.12	-10000	0	-0.22	64	64
HCK	0.036	0.013	-10000	0	0	65	65
CRK	0.038	0.012	-10000	0	0	49	49
TYK2	-0.037	0.12	0.23	24	-0.25	79	103
EGF	0.037	0.016	-10000	0	-0.009	52	52
YES1	0.037	0.012	-10000	0	0	51	51
CAV1	-0.036	0.11	0.19	1	-0.24	77	78
TXN	0.037	0.012	-10000	0	0	49	49
PTP1B/IRS1/GRB2	-0.027	0.13	-10000	0	-0.24	95	95
cell migration	0.052	0.11	0.25	95	-10000	0	95
STAT3	0.038	0.011	-10000	0	0	41	41
PRLR	0.038	0.016	-10000	0	-10000	0	0
ITGA2B	0.039	0.008	-10000	0	0	22	22
CSF1R	0.034	0.016	-10000	0	0	94	94
Prolactin Receptor/Prolactin	0.056	0.028	-10000	0	-10000	0	0
FGR	0.04	0.007	-10000	0	0	15	15
PTP1B/p130 Cas	-0.035	0.12	-10000	0	-0.24	91	91
Crk/p130 Cas	-0.028	0.12	-10000	0	-0.24	87	87
DOK1	-0.038	0.11	0.21	2	-0.24	75	77
JAK2	-0.031	0.14	-10000	0	-0.41	56	56
Jak2/Leptin Receptor/Leptin	-0.026	0.14	-10000	0	-0.28	80	80
PIK3R1	0.034	0.016	-10000	0	0	99	99
PTPN1	-0.053	0.11	-10000	0	-0.25	95	95
LYN	0.035	0.015	-10000	0	0	83	83
CDH2	0.019	0.021	-10000	0	0	290	290
SRC	0.003	0.1	-10000	0	-0.5	17	17
ITGB3	0.032	0.017	-10000	0	0	116	116
CAT1/PTP1B	-0.041	0.13	0.22	7	-0.28	81	88
CAPN1	0.038	0.009	-10000	0	0	25	25
CSK	0.039	0.009	-10000	0	0	25	25
PI3K	-0.012	0.11	-10000	0	-0.23	49	49
mol:H2O2	0.002	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.022	0.14	-10000	0	-0.26	76	76
negative regulation of transcription	-0.03	0.14	-10000	0	-0.4	56	56
FCGR2A	0.032	0.017	-10000	0	0	119	119
FER	0.037	0.011	-10000	0	0	44	44
alphaIIb/beta3 Integrin	0.037	0.05	-10000	0	-0.14	35	35
BLK	0.033	0.017	-10000	0	0	114	114
Insulin Receptor/Insulin/Shc	0.068	0.036	-10000	0	-0.12	5	5
RHOA	0.039	0.006	-10000	0	0	13	13
LEPR	0.039	0.011	-10000	0	0	40	40
BCAR1	0.036	0.013	-10000	0	0	65	65
p210 bcr-abl/Grb2	0.04	0.008	-10000	0	0	21	21
mol:NADPH	-0.001	0.002	-10000	0	-10000	0	0
TRPV6	-0.011	0.12	0.2	3	-0.3	49	52
PRL	0.042	0.011	-10000	0	-10000	0	0
SOCS3	-0.029	0.27	-10000	0	-1.2	28	28
SPRY2	0.023	0.021	-10000	0	0	240	240
Insulin Receptor/Insulin/IRS1	0.068	0.038	-10000	0	-0.12	8	8
CSF1/CSF1R	-0.043	0.14	-10000	0	-0.26	100	100
Ras protein signal transduction	0.011	0.091	0.6	11	-10000	0	11
IRS1	0.04	0.008	-10000	0	0	22	22
INS	0.039	0.01	-10000	0	0	30	30
LEP	0.039	0.008	-10000	0	0	22	22
STAT5B	-0.041	0.13	-10000	0	-0.27	87	87
STAT5A	-0.043	0.13	-10000	0	-0.27	88	88
GRB2	0.04	0.008	-10000	0	0	21	21
PDGFB-D/PDGFRB	-0.042	0.12	-10000	0	-0.24	94	94
CSN2	0.039	0.06	0.43	1	-10000	0	1
PIK3CA	0.029	0.019	-10000	0	0	166	166
LAT	-0.059	0.19	-10000	0	-0.48	85	85
YBX1	0.049	0.019	-10000	0	-0.28	1	1
LCK	0.039	0.009	-10000	0	0	25	25
SHC1	0.039	0.008	-10000	0	0	23	23
NOX4	0.021	0.021	-10000	0	0	277	277

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.041	0.004	-10000	0	0	6	6
PTK2	0.027	0.019	-10000	0	0	182	182
CRKL	-0.022	0.051	0.11	12	-0.13	68	80
GRB2/SOS1/SHC	0.065	0.049	-10000	0	-0.12	24	24
HRAS	0.039	0.01	-10000	0	0	31	31
IRS1/Crk	0.011	0.056	-10000	0	-0.12	73	73
IGF-1R heterotetramer/IGF1/PTP1B	0.034	0.07	-10000	0	-0.12	70	70
AKT1	0.008	0.096	0.18	101	-0.17	15	116
BAD	0.001	0.09	0.16	100	-0.17	14	114
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.02	0.051	0.12	13	-0.13	64	77
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.013	0.07	0.2	8	-0.13	84	92
RAF1	0.024	0.12	0.28	15	-0.51	11	26
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.045	0.085	0.21	3	-0.13	83	86
YWHAZ	0.034	0.016	-10000	0	0	96	96
IGF-1R heterotetramer/IGF1/IRS1	0.019	0.067	0.18	3	-0.13	82	85
PIK3CA	0.029	0.019	-10000	0	0	166	166
RPS6KB1	0.009	0.098	0.18	105	-0.18	17	122
GNB2L1	0.039	0.009	-10000	0	0	30	30
positive regulation of MAPKKK cascade	0.023	0.11	0.27	20	-0.41	10	30
PXN	0.04	0.006	-10000	0	0	10	10
PIK3R1	0.034	0.016	-10000	0	0	99	99
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.047	0.044	-10000	0	-0.14	24	24
HRAS/GTP	0.015	0.065	-10000	0	-0.13	75	75
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.063	0.087	-10000	0	-0.12	77	77
IGF-1R heterotetramer	0.034	0.023	0.099	3	-0.054	13	16
IGF-1R heterotetramer/IGF1/IRS/Nck	0.035	0.075	0.19	3	-0.12	82	85
Crk/p130 Cas/Paxillin	0.043	0.081	0.25	9	-0.13	70	79
IGF1R	0.034	0.023	0.099	3	-0.054	13	16
IGF1	0.027	0.034	0.099	3	-0.053	67	70
IRS2/Crk	0.01	0.054	0.17	3	-0.13	59	62
PI3K	0.023	0.079	0.21	1	-0.12	88	89
apoptosis	-0.008	0.094	0.17	8	-0.18	83	91
HRAS/GDP	0.029	0.007	-10000	0	-10000	0	0
PRKCD	-0.014	0.092	0.21	3	-0.22	65	68
RAF1/14-3-3 E	0.036	0.12	0.28	14	-0.44	11	25
BAD/14-3-3	0.008	0.097	0.19	83	-0.17	14	97
PRKCZ	0.007	0.095	0.18	100	-0.17	15	115
Crk/p130 Cas/Paxillin/FAK1	0.016	0.08	0.19	18	-0.16	35	53
PTPN1	0.037	0.012	-10000	0	0	55	55
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.012	0.095	-10000	0	-0.22	67	67
BCAR1	0.036	0.013	-10000	0	0	65	65
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.056	0.076	-10000	0	-0.11	72	72
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.037	0.012	-10000	0	0	51	51
IRS1/NCK2	0.025	0.067	0.14	15	-0.12	82	97
GRB10	0.04	0.008	-10000	0	0	22	22
PTPN11	-0.02	0.052	0.12	13	-0.13	66	79
IRS1	0.005	0.06	0.13	17	-0.13	80	97
IRS2	-0.021	0.051	0.12	14	-0.13	67	81
IGF-1R heterotetramer/IGF1	0.021	0.074	0.16	3	-0.16	72	75
GRB2	0.04	0.008	-10000	0	0	21	21
PDPK1	0.015	0.1	0.19	103	-0.18	14	117
YWHAE	0.037	0.013	-10000	0	0	58	58
PRKD1	-0.016	0.095	0.21	1	-0.22	69	70
SHC1	0.039	0.008	-10000	0	0	23	23

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.027	0.1	0.21	15	-0.24	33	48
TBX21	-0.026	0.27	-10000	0	-0.69	51	51
B2M	0.038	0.013	-10000	0	-10000	0	0
TYK2	0.024	0.043	-10000	0	-0.048	101	101
IL12RB1	0.023	0.044	-10000	0	-0.049	107	107
GADD45B	-0.058	0.34	-10000	0	-0.88	58	58
IL12RB2	0.027	0.045	-10000	0	-0.048	111	111
GADD45G	-0.032	0.3	-10000	0	-0.72	59	59
natural killer cell activation	0.002	0.021	0.043	11	-0.033	96	107
RELB	0.039	0.01	-10000	0	0	33	33
RELA	0.04	0.006	-10000	0	0	10	10
IL18	0.03	0.024	-10000	0	-0.042	19	19
IL2RA	0.038	0.01	-10000	0	0	38	38
IFNG	0.037	0.013	-10000	0	0	58	58
STAT3 (dimer)	-0.025	0.28	0.4	2	-0.57	84	86
HLA-DRB5	0.016	0.027	-10000	0	-0.006	297	297
FASLG	-0.025	0.28	0.52	1	-0.71	49	50
NF kappa B2 p52/RelB	-0.013	0.28	-10000	0	-0.56	84	84
CD4	0.025	0.028	-10000	0	-0.013	179	179
SOCS1	0.037	0.012	-10000	0	0	51	51
EntrezGene:6955	-0.001	0.01	-10000	0	-0.026	59	59
CD3D	0.026	0.03	-10000	0	-0.039	67	67
CD3E	0.028	0.029	-10000	0	-0.038	68	68
CD3G	0.025	0.029	-10000	0	-0.041	57	57
IL12Rbeta2/JAK2	0.029	0.074	-10000	0	-0.13	44	44
CCL3	-0.043	0.32	0.47	1	-0.79	61	62
CCL4	-0.03	0.27	-10000	0	-0.56	84	84
HLA-A	0.038	0.013	-10000	0	-10000	0	0
IL18/IL18R	0.053	0.082	-10000	0	-0.12	73	73
NOS2	-0.026	0.27	0.38	2	-0.54	82	84
IL12/IL12R/TYK2/JAK2/SPHK2	0.027	0.1	0.21	17	-0.23	37	54
IL1R1	-0.11	0.43	-10000	0	-0.97	96	96
IL4	0.02	0.044	0.092	6	-0.058	17	23
JAK2	0.023	0.042	-10000	0	-0.049	88	88
EntrezGene:6957	-0.001	0.009	-10000	0	-0.024	36	36
TCR/CD3/MHC I/CD8	-0.013	0.11	-10000	0	-0.42	26	26
RAB7A	-0.031	0.27	0.38	1	-0.57	79	80
lysosomal transport	-0.027	0.26	0.37	1	-0.55	79	80
FOS	-0.18	0.51	-10000	0	-1.1	124	124
STAT4 (dimer)	-0.022	0.29	0.4	5	-0.6	77	82
STAT5A (dimer)	-0.02	0.28	-10000	0	-0.57	81	81
GZMA	-0.051	0.34	-10000	0	-0.87	58	58
GZMB	-0.034	0.3	0.43	1	-0.72	63	64
HLX	0	0	-10000	0	-10000	0	0
LCK	-0.039	0.28	0.4	3	-0.59	83	86
TCR/CD3/MHC II/CD4	-0.066	0.2	-10000	0	-0.36	128	128
IL2/IL2R	0.045	0.08	-10000	0	-0.11	90	90
MAPK14	-0.047	0.32	-10000	0	-0.7	78	78
CCR5	-0.02	0.25	0.37	2	-0.5	85	87
IL1B	0.023	0.041	-10000	0	-0.048	88	88
STAT6	0.009	0.14	-10000	0	-0.56	13	13
STAT4	0.039	0.008	-10000	0	0	24	24
STAT3	0.038	0.011	-10000	0	0	41	41
STAT1	0.034	0.016	-10000	0	0	102	102
NFKB1	0.036	0.013	-10000	0	0	66	66
NFKB2	0.04	0.007	-10000	0	0	18	18
IL12B	0.027	0.045	-10000	0	-0.048	114	114
CD8A	0.042	0.005	-10000	0	-10000	0	0
CD8B	0.001	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.028	0.1	0.23	33	-0.21	16	49
IL2RB	0.035	0.014	-10000	0	0	76	76
proteasomal ubiquitin-dependent protein catabolic process	-0.015	0.27	0.39	5	-0.56	77	82
IL2RG	0.028	0.019	-10000	0	0	179	179
IL12	0.024	0.072	-10000	0	-0.13	44	44
STAT5A	0.038	0.01	-10000	0	0	36	36
CD247	-0.001	0.009	-10000	0	-0.024	38	38
IL2	0.039	0.01	-10000	0	0	34	34
SPHK2	0.04	0.008	-10000	0	0	20	20
FRAP1	0.039	0.009	-10000	0	0	28	28
IL12A	0.02	0.04	-10000	0	-0.049	83	83
IL12/IL12R/TYK2/JAK2	-0.047	0.29	-10000	0	-0.63	80	80
MAP2K3	-0.05	0.33	0.41	1	-0.72	79	80
RIPK2	0.032	0.017	-10000	0	0	119	119
MAP2K6	-0.055	0.31	-10000	0	-0.67	83	83
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.023	0.029	-10000	0	-0.012	203	203
IL18RAP	0.039	0.019	-10000	0	-0.041	23	23
IL12Rbeta1/TYK2	0.038	0.057	-10000	0	-0.079	21	21
EOMES	0.005	0.072	-10000	0	-0.55	7	7
STAT1 (dimer)	-0.043	0.28	0.4	2	-0.58	86	88
T cell proliferation	-0.021	0.23	0.35	6	-0.48	80	86
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.039	0.019	-10000	0	-0.041	22	22
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.029	0.25	-10000	0	-0.53	76	76
ATF2	-0.046	0.3	-10000	0	-0.65	79	79

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.037	0.012	-10000	0	0	53	53
LAT2	-0.019	0.1	0.19	5	-0.22	87	92
AP1	-0.025	0.18	0.28	3	-0.41	66	69
mol:PIP3	-0.031	0.13	0.26	10	-0.31	64	74
IKBKB	-0.011	0.09	0.2	25	-0.19	57	82
AKT1	0.02	0.12	0.25	67	-0.21	10	77
IKBKG	-0.019	0.084	0.2	8	-0.19	60	68
MS4A2	0.046	0.012	0.07	38	-0.004	10	48
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.029	0.019	-10000	0	0	166	166
MAP3K1	-0.006	0.14	0.24	50	-0.29	61	111
mol:Ca2+	-0.022	0.11	0.22	12	-0.25	58	70
LYN	0.035	0.018	0.078	1	-0.003	92	93
CBLB	-0.014	0.095	0.18	7	-0.21	77	84
SHC1	0.039	0.008	-10000	0	0	23	23
RasGAP/p62DOK	0.023	0.071	-10000	0	-0.1	103	103
positive regulation of cell migration	-0.01	0.001	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
PLD2	-0.012	0.075	0.29	16	-0.16	4	20
PTPN13	-0.059	0.2	-10000	0	-0.69	33	33
PTPN11	0.039	0.019	0.081	3	-0.033	22	25
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.005	0.13	0.28	20	-0.33	30	50
SYK	0.037	0.017	0.078	1	-0.003	74	75
GRB2	0.04	0.008	-10000	0	0	21	21
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.024	0.13	0.18	1	-0.27	91	92
LAT	-0.017	0.097	0.2	1	-0.21	84	85
PAK2	-0.002	0.15	0.24	58	-0.3	66	124
NFATC2	0.003	0.054	-10000	0	-0.39	9	9
HRAS	-0.026	0.14	0.27	3	-0.32	71	74
GAB2	0.031	0.018	-10000	0	0	136	136
PLA2G1B	0.012	0.14	-10000	0	-0.9	12	12
Fc epsilon R1	0.033	0.071	-10000	0	-0.093	111	111
Antigen/IgE/Fc epsilon R1	0.035	0.063	-10000	0	-0.079	102	102
mol:GDP	-0.025	0.16	0.23	5	-0.4	58	63
JUN	0.035	0.014	-10000	0	0	76	76
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.034	0.016	-10000	0	0	99	99
FOS	0.026	0.02	-10000	0	0	201	201
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.011	0.1	0.14	8	-0.22	85	93
CHUK	-0.021	0.085	0.19	11	-0.19	66	77
KLRG1	-0.016	0.079	-10000	0	-0.17	84	84
VAV1	-0.013	0.094	0.17	5	-0.22	72	77
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.017	0.097	0.18	4	-0.21	82	86
negative regulation of mast cell degranulation	-0.021	0.074	-10000	0	-0.19	50	50
BTK	-0.033	0.18	-10000	0	-0.48	53	53
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.026	0.1	-10000	0	-0.21	105	105
GAB2/PI3K/SHP2	-0.038	0.053	-10000	0	-0.15	64	64
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	0	0.058	-10000	0	-0.13	77	77
RAF1	0.015	0.15	-10000	0	-0.99	12	12
Fc epsilon R1/FcgammaRIIB/SHIP	0.032	0.091	-10000	0	-0.12	124	124
FCER1G	0.027	0.02	-10000	0	0	189	189
FCER1A	0.039	0.014	-10000	0	-0.006	41	41
Antigen/IgE/Fc epsilon R1/Fyn	0.04	0.076	-10000	0	-0.09	107	107
MAPK3	0.012	0.14	-10000	0	-0.91	12	12
MAPK1	0.006	0.14	-10000	0	-0.92	12	12
NFKB1	0.036	0.013	-10000	0	0	66	66
MAPK8	-0.035	0.22	-10000	0	-0.58	57	57
DUSP1	0.026	0.02	-10000	0	0	196	196
NF-kappa-B/RelA	0.002	0.069	0.14	16	-0.14	61	77
actin cytoskeleton reorganization	-0.052	0.2	-10000	0	-0.73	30	30
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.018	0.13	0.26	5	-0.27	75	80
FER	-0.017	0.096	0.2	1	-0.22	78	79
RELA	0.04	0.006	-10000	0	0	10	10
ITK	-0.002	0.056	-10000	0	-0.29	15	15
SOS1	0.037	0.012	-10000	0	0	51	51
PLCG1	-0.026	0.15	0.3	4	-0.35	69	73
cytokine secretion	-0.002	0.047	0.083	8	-0.098	63	71
SPHK1	-0.016	0.098	0.19	6	-0.21	83	89
PTK2	-0.056	0.21	-10000	0	-0.78	30	30
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.018	0.14	-10000	0	-0.28	90	90
EDG1	-0.01	0.001	-10000	0	-10000	0	0
mol:DAG	-0.031	0.14	0.26	10	-0.31	67	77
MAP2K2	0.005	0.14	-10000	0	-0.92	12	12
MAP2K1	0.004	0.14	-10000	0	-0.92	12	12
MAP2K7	0.038	0.011	-10000	0	0	41	41
KLRG1/SHP2	0.011	0.09	0.2	30	-0.18	53	83
MAP2K4	-0.081	0.34	-10000	0	-0.9	78	78
Fc epsilon R1/FcgammaRIIB	0.034	0.098	-10000	0	-0.13	124	124
mol:Choline	-0.012	0.074	0.29	16	-0.16	4	20
SHC/Grb2/SOS1	0.023	0.13	0.24	1	-0.21	91	92
FYN	0.034	0.016	-10000	0	0	94	94
DOK1	0.04	0.008	-10000	0	0	22	22
PXN	-0.054	0.2	-10000	0	-0.7	30	30
HCLS1	-0.012	0.1	0.18	7	-0.24	62	69
PRKCB	-0.023	0.11	0.22	10	-0.24	68	78
FCGR2B	0.03	0.019	-10000	0	0	153	153
IGHE	0	0.006	0.037	1	-10000	0	1
KLRG1/SHIP	-0.021	0.075	-10000	0	-0.2	50	50
LCP2	0.034	0.016	-10000	0	0	101	101
PLA2G4A	-0.008	0.09	0.15	5	-0.22	63	68
RASA1	0.037	0.013	-10000	0	0	56	56
mol:Phosphatidic acid	-0.012	0.074	0.29	16	-0.16	4	20
IKK complex	-0.014	0.075	0.19	18	-0.16	46	64
WIPF1	0	0	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.032	0.017	-10000	0	0	116	116
ANTXR2	0.035	0.015	-10000	0	0	87	87
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.006	0.011	-10000	0	-0.033	72	72
monocyte activation	-0.082	0.17	-10000	0	-0.35	150	150
MAP2K2	-0.041	0.18	-10000	0	-0.58	55	55
MAP2K1	-0.011	0.011	0.008	38	-0.037	68	106
MAP2K7	-0.01	0.011	0.008	36	-0.037	65	101
MAP2K6	-0.009	0.012	0.008	33	-0.039	58	91
CYAA	-0.023	0.033	-10000	0	-0.1	72	72
MAP2K4	-0.01	0.012	0.008	32	-0.038	64	96
IL1B	-0.01	0.038	0.1	9	-0.084	75	84
Channel	0.022	0.056	-10000	0	-0.11	72	72
NLRP1	-0.006	0.01	-10000	0	-0.031	72	72
CALM1	0.039	0.009	-10000	0	0	26	26
negative regulation of phagocytosis	0.001	0.074	-10000	0	-0.43	15	15
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.006	0.011	0.033	72	-10000	0	72
MAPK3	-0.011	0.012	0.008	37	-0.037	71	108
MAPK1	-0.01	0.011	0.008	35	-0.037	64	99
PGR	-0.008	0.011	0.009	37	-0.037	51	88
PA/Cellular Receptors	0.023	0.062	-10000	0	-0.12	72	72
apoptosis	-0.006	0.011	-10000	0	-0.033	72	72
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.021	0.056	-10000	0	-0.11	72	72
macrophage activation	-0.01	0.03	0.17	10	-0.11	2	12
TNF	0.04	0.008	-10000	0	0	22	22
VCAM1	-0.081	0.17	-10000	0	-0.36	148	148
platelet activation	0.001	0.074	-10000	0	-0.43	15	15
MAPKKK cascade	0.008	0.027	0.083	9	-0.071	19	28
IL18	-0.006	0.038	0.1	10	-0.084	63	73
negative regulation of macrophage activation	-0.006	0.011	-10000	0	-0.033	72	72
LEF	-0.006	0.011	-10000	0	-0.033	72	72
CASP1	0	0.012	0.019	35	-0.03	48	83
mol:cAMP	0.001	0.074	-10000	0	-0.43	15	15
necrosis	-0.006	0.011	-10000	0	-0.033	72	72
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.023	0.053	-10000	0	-0.1	72	72
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.054	0.062	0.15	116	-0.032	30	146
AES	0.052	0.054	0.13	119	-0.032	13	132
FBXW11	0.04	0.008	-10000	0	0	22	22
mol:GTP	0.001	0.003	0.033	1	-10000	0	1
LRP6/FZD1	0.042	0.048	-10000	0	-0.13	32	32
SMAD4	0.038	0.011	-10000	0	0	43	43
DKK2	0.039	0.01	-10000	0	0	33	33
TLE1	0.052	0.051	0.13	114	-0.033	11	125
MACF1	0.033	0.016	-10000	0	0	106	106
CTNNB1	0.029	0.12	0.3	24	-0.42	12	36
WIF1	0.039	0.009	-10000	0	-0.001	27	27
beta catenin/RanBP3	0.092	0.22	0.46	112	-0.39	10	122
KREMEN2	0.039	0.009	-10000	0	0	29	29
DKK1	0.038	0.011	-10000	0	0	39	39
beta catenin/beta TrCP1	0.049	0.12	0.31	24	-0.4	12	36
FZD1	0.04	0.006	-10000	0	0	13	13
AXIN2	-0.051	0.21	0.8	2	-0.81	25	27
AXIN1	0.039	0.011	-10000	0	0	39	39
RAN	0.04	0.009	0.075	1	0	21	22
Axin1/APC/GSK3/beta catenin	0.02	0.14	0.41	1	-0.48	32	33
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	-0.026	0.17	0.28	8	-0.37	76	84
Axin1/APC/GSK3	0.024	0.079	0.2	13	-0.26	15	28
Axin1/APC/GSK3/beta catenin/Macf1	0.017	0.088	0.28	10	-0.3	14	24
HNF1A	0.018	0.05	0.089	131	-10000	0	131
CTBP1	0.053	0.052	0.13	116	-0.033	11	127
MYC	0.037	0.53	0.64	141	-1.1	67	208
RANBP3	0.039	0.012	0.075	1	0	42	43
DKK2/LRP6/Kremen 2	0.058	0.053	-10000	0	-0.12	29	29
NKD1	0.038	0.011	-10000	0	0	43	43
TCF4	0.054	0.057	0.14	116	-0.032	11	127
TCF3	0.051	0.052	0.13	117	-0.033	12	129
WNT1/LRP6/FZD1/Axin1	0.075	0.061	-10000	0	-0.11	30	30
Ran/GTP	0.03	0.014	0.1	1	-0.12	3	4
CtBP/CBP/TCF/TLE1/AES	0.051	0.3	0.54	110	-0.36	34	144
LEF1	0.036	0.048	0.13	73	-0.032	12	85
DVL1	0.028	0.081	0.23	10	-0.32	13	23
CSNK2A1	0.038	0.012	-10000	0	0	47	47
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.065	0.19	-10000	0	-0.4	91	91
DKK1/LRP6/Kremen 2	0.056	0.053	-10000	0	-0.12	28	28
LRP6	0.034	0.016	-10000	0	0	94	94
CSNK1A1	0.057	0.064	0.15	127	-0.032	33	160
NLK	0.029	0.026	-10000	0	-0.035	68	68
CCND1	-0.18	0.5	0.72	11	-1.2	94	105
WNT1	0.041	0.006	-10000	0	0	10	10
GSK3A	0.038	0.012	0.065	1	0	46	47
GSK3B	0.039	0.008	-10000	0	0	23	23
FRAT1	0.039	0.009	-10000	0	-0.004	19	19
PPP2R5D	0.031	0.071	0.24	2	-0.38	10	12
APC	-0.006	0.077	0.2	57	-10000	0	57
WNT1/LRP6/FZD1	0.018	0.064	0.18	3	-0.24	10	13
CREBBP	0.052	0.053	0.13	118	-0.033	14	132

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.064	0.21	-10000	0	-0.35	163	163
Syndecan-4/Syndesmos	-0.039	0.19	0.3	2	-0.47	54	56
positive regulation of JNK cascade	-0.058	0.19	0.3	1	-0.43	71	72
Syndecan-4/ADAM12	-0.055	0.18	0.3	2	-0.46	58	60
CCL5	0.029	0.019	-10000	0	0	160	160
Rac1/GDP	0.029	0.009	-10000	0	-0.12	1	1
DNM2	0.036	0.014	-10000	0	0	72	72
ITGA5	0.036	0.013	-10000	0	0	64	64
SDCBP	0.035	0.014	-10000	0	0	77	77
PLG	0.033	0.028	-10000	0	-0.042	50	50
ADAM12	0.03	0.018	-10000	0	0	152	152
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.039	0.01	-10000	0	0	33	33
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.023	0.022	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.042	0.18	-10000	0	-0.46	53	53
Syndecan-4/CXCL12/CXCR4	-0.061	0.2	0.31	1	-0.46	70	71
Syndecan-4/Laminin alpha3	-0.049	0.19	0.3	1	-0.47	56	57
MDK	0.039	0.008	-10000	0	0	23	23
Syndecan-4/FZD7	-0.042	0.19	0.3	2	-0.47	56	58
Syndecan-4/Midkine	-0.04	0.19	0.3	2	-0.47	55	57
FZD7	0.036	0.013	-10000	0	0	64	64
Syndecan-4/FGFR1/FGF	-0.028	0.18	-10000	0	-0.45	48	48
THBS1	0.027	0.02	-10000	0	0	190	190
integrin-mediated signaling pathway	-0.056	0.18	0.3	2	-0.42	78	80
positive regulation of MAPKKK cascade	-0.058	0.19	0.3	1	-0.43	71	72
Syndecan-4/TACI	-0.039	0.19	0.3	2	-0.47	55	57
CXCR4	0.033	0.017	-10000	0	0	115	115
cell adhesion	-0.035	0.092	0.21	2	-0.2	120	122
Syndecan-4/Dynamin	-0.037	0.18	-10000	0	-0.47	49	49
Syndecan-4/TSP1	-0.059	0.19	0.3	2	-0.46	61	63
Syndecan-4/GIPC	-0.037	0.18	-10000	0	-0.48	46	46
Syndecan-4/RANTES	-0.051	0.19	0.3	1	-0.47	61	62
ITGB1	0.038	0.01	-10000	0	0	36	36
LAMA1	0.033	0.016	-10000	0	0	104	104
LAMA3	0.03	0.018	-10000	0	0	151	151
RAC1	0.039	0.009	-10000	0	0	28	28
PRKCA	0	0.1	0.9	5	-10000	0	5
Syndecan-4/alpha-Actinin	-0.04	0.19	0.3	2	-0.47	56	58
TFPI	0.039	0.01	-10000	0	0	32	32
F2	0.037	0.026	0.087	2	-0.037	49	51
alpha5/beta1 Integrin	0.043	0.046	-10000	0	-0.13	29	29
positive regulation of cell adhesion	-0.056	0.17	-10000	0	-0.45	55	55
ACTN1	0.039	0.01	-10000	0	0	32	32
TNC	0.027	0.02	-10000	0	0	189	189
Syndecan-4/CXCL12	-0.058	0.19	0.3	2	-0.46	65	67
FGF6	0.037	0.012	-10000	0	0	55	55
RHOA	0.04	0.006	-10000	0	0	13	13
CXCL12	0.028	0.019	-10000	0	0	174	174
TNFRSF13B	0.037	0.012	-10000	0	0	50	50
FGF2	0.039	0.01	-10000	0	0	33	33
FGFR1	0.033	0.017	-10000	0	0	112	112
Syndecan-4/PI-4-5-P2	-0.062	0.17	-10000	0	-0.46	56	56
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.017	0.024	-10000	0	-0.04	24	24
cell migration	-0.011	0.013	-10000	0	-10000	0	0
PRKCD	0.033	0.027	-10000	0	-0.042	44	44
vasculogenesis	-0.056	0.18	0.3	2	-0.44	62	64
SDC4	-0.055	0.18	-10000	0	-0.5	50	50
Syndecan-4/Tenascin C	-0.059	0.19	0.3	2	-0.46	65	67
Syndecan-4/PI-4-5-P2/PKC alpha	-0.019	0.017	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.041	0.19	0.3	2	-0.48	52	54
MMP9	0.027	0.023	-10000	0	-0.038	18	18
Rac1/GTP	-0.036	0.094	0.21	2	-0.2	120	122
cytoskeleton organization	-0.037	0.18	0.3	2	-0.4	73	75
GIPC1	0.034	0.015	-10000	0	0	92	92
Syndecan-4/TFPI	-0.04	0.19	0.3	2	-0.46	57	59

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.006	0.051	-10000	0	-0.15	42	42
EPHB2	0.038	0.01	-10000	0	0	38	38
Syndecan-2/TACI	0.024	0.041	-10000	0	-0.1	39	39
LAMA1	0.033	0.016	-10000	0	0	104	104
Syndecan-2/alpha2 ITGB1	0.034	0.088	0.19	40	-0.12	88	128
HRAS	0.039	0.01	-10000	0	0	31	31
Syndecan-2/CASK	0	0.028	-10000	0	-0.097	42	42
ITGA5	0.036	0.013	-10000	0	0	64	64
BAX	0.023	0.068	-10000	0	-10000	0	0
EPB41	0.039	0.01	-10000	0	0	31	31
positive regulation of cell-cell adhesion	0.016	0.045	-10000	0	-0.096	67	67
LAMA3	0.03	0.018	-10000	0	0	151	151
EZR	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.033	0.016	-10000	0	0	105	105
Syndecan-2/MMP2	0.007	0.053	-10000	0	-0.16	42	42
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.034	0.057	-10000	0	-0.14	46	46
dendrite morphogenesis	0.024	0.043	-10000	0	-0.11	39	39
Syndecan-2/GM-CSF	0.025	0.041	-10000	0	-0.1	41	41
determination of left/right symmetry	0.01	0.007	-10000	0	-10000	0	0
Syndecan-2/PKC delta	0.023	0.041	-10000	0	-0.11	40	40
GNB2L1	0.039	0.009	-10000	0	0	30	30
MAPK3	0.012	0.077	0.15	108	-0.099	39	147
MAPK1	0.011	0.076	0.15	104	-0.099	38	142
Syndecan-2/RACK1	0.038	0.047	-10000	0	-0.091	44	44
NF1	0.034	0.016	-10000	0	0	96	96
FGFR/FGF/Syndecan-2	0.01	0.007	-10000	0	-10000	0	0
ITGA2	0.033	0.017	-10000	0	0	114	114
MAPK8	-0.004	0.005	-10000	0	-10000	0	0
Syndecan-2/alpha2/beta1 Integrin	0.048	0.08	0.19	50	-0.11	57	107
Syndecan-2/Kininogen	0.022	0.039	-10000	0	-0.1	36	36
ITGB1	0.038	0.01	-10000	0	0	36	36
SRC	0.008	0.076	0.19	66	-10000	0	66
Syndecan-2/CASK/Protein 4.1	0.022	0.037	-10000	0	-0.092	43	43
extracellular matrix organization	0.022	0.042	-10000	0	-0.11	39	39
actin cytoskeleton reorganization	0.006	0.051	-10000	0	-0.15	42	42
Syndecan-2/Caveolin-2/Ras	0.028	0.059	-10000	0	-0.11	64	64
Syndecan-2/Laminin alpha3	0.017	0.046	-10000	0	-0.13	35	35
Syndecan-2/RasGAP	0.062	0.068	0.18	52	-0.092	56	108
alpha5/beta1 Integrin	0.043	0.046	-10000	0	-0.13	29	29
PRKCD	0.037	0.012	-10000	0	0	51	51
Syndecan-2 dimer	0.024	0.043	-10000	0	-0.11	39	39
GO:0007205	0.003	0.001	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.039	0.059	0.2	3	-0.097	49	52
RHOA	0.04	0.006	-10000	0	0	13	13
SDCBP	0.035	0.014	-10000	0	0	77	77
TNFRSF13B	0.037	0.012	-10000	0	0	50	50
RASA1	0.037	0.013	-10000	0	0	56	56
alpha2/beta1 Integrin	0.034	0.057	-10000	0	-0.14	46	46
Syndecan-2/Synbindin	0.019	0.044	-10000	0	-0.11	41	41
TGFB1	0.036	0.014	-10000	0	0	69	69
CASP3	0.008	0.075	0.15	94	-0.1	49	143
FN1	0.021	0.021	-10000	0	0	268	268
Syndecan-2/IL8	0.018	0.044	-10000	0	-0.12	39	39
SDC2	0.01	0.007	-10000	0	-10000	0	0
KNG1	0.034	0.016	-10000	0	0	100	100
Syndecan-2/Neurofibromin	0.021	0.042	-10000	0	-0.11	37	37
TRAPPC4	0.034	0.016	-10000	0	0	97	97
CSF2	0.04	0.008	-10000	0	0	21	21
Syndecan-2/TGFB1	0.022	0.042	-10000	0	-0.11	39	39
Syndecan-2/Syntenin/PI-4-5-P2	0.016	0.045	-10000	0	-0.096	67	67
Syndecan-2/Ezrin	0.023	0.038	-10000	0	-0.093	45	45
PRKACA	0.004	0.071	0.15	80	-0.1	53	133
angiogenesis	0.018	0.044	-10000	0	-0.12	39	39
MMP2	0.021	0.021	-10000	0	0	265	265
IL8	0.031	0.018	-10000	0	0	129	129
calcineurin-NFAT signaling pathway	0.024	0.04	-10000	0	-0.1	39	39

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.081	0.35	0.49	2	-0.79	81	83
CRP	-0.08	0.33	0.5	1	-0.78	74	75
cell cycle arrest	-0.12	0.39	-10000	0	-0.87	91	91
TIMP1	-0.1	0.36	-10000	0	-0.76	107	107
IL6ST	0.025	0.036	-10000	0	-0.043	65	65
Rac1/GDP	-0.008	0.17	0.29	7	-0.38	58	65
AP1	-0.027	0.21	-10000	0	-0.48	65	65
GAB2	0.032	0.02	-10000	0	-0.045	2	2
TNFSF11	-0.084	0.33	-10000	0	-0.77	77	77
HSP90B1	0.011	0.093	-10000	0	-1.1	2	2
GAB1	0.038	0.014	-10000	0	-0.04	2	2
MAPK14	-0.029	0.17	-10000	0	-0.62	30	30
AKT1	-0.004	0.15	0.28	3	-0.45	31	34
FOXO1	-0.005	0.14	0.26	3	-0.44	30	33
MAP2K6	-0.021	0.15	0.22	1	-0.42	48	49
mol:GTP	0	0.003	-10000	0	-10000	0	0
MAP2K4	-0.034	0.2	0.31	9	-0.43	79	88
MITF	-0.016	0.15	0.23	5	-0.35	58	63
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.036	0.013	-10000	0	0	65	65
A2M	-0.12	0.41	-10000	0	-1.2	66	66
CEBPB	0.036	0.014	-10000	0	0	72	72
GRB2/SOS1/GAB family/SHP2	-0.009	0.16	0.31	3	-0.4	56	59
STAT3	-0.14	0.42	-10000	0	-0.96	91	91
STAT1	-0.071	0.28	-10000	0	-0.83	64	64
CEBPD	-0.083	0.34	0.52	2	-0.79	75	77
PIK3CA	0.029	0.02	-10000	0	-0.047	2	2
PI3K	0.023	0.06	-10000	0	-0.15	46	46
JUN	0.036	0.014	-10000	0	0	76	76
PIAS3/MITF	-0.004	0.15	-10000	0	-0.34	53	53
MAPK11	-0.026	0.16	-10000	0	-0.6	30	30
STAT3 (dimer)/FOXO1	-0.089	0.36	0.41	2	-0.74	98	100
GRB2/SOS1/GAB family	0.03	0.13	0.3	4	-0.29	31	35
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	0.001	0.11	0.19	3	-0.27	54	57
GRB2	0.041	0.01	-10000	0	-0.002	22	22
JAK2	0.034	0.016	-10000	0	0	101	101
LBP	-0.031	0.26	0.47	1	-0.57	71	72
PIK3R1	0.034	0.017	-10000	0	-0.001	102	102
JAK1	0.032	0.029	-10000	0	-0.043	58	58
MYC	-0.071	0.42	0.5	8	-0.87	97	105
FGG	-0.083	0.33	-10000	0	-0.76	78	78
macrophage differentiation	-0.12	0.39	-10000	0	-0.87	91	91
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.049	0.1	-10000	0	-0.18	48	48
JUNB	-0.097	0.39	0.5	7	-0.86	94	101
FOS	0.026	0.02	-10000	0	0	201	201
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.01	0.16	0.22	5	-0.36	63	68
STAT1/PIAS1	-0.015	0.18	0.28	2	-0.36	76	78
GRB2/SOS1/GAB family/SHP2/PI3K	-0.008	0.15	-10000	0	-0.41	43	43
STAT3 (dimer)	-0.14	0.41	-10000	0	-0.93	91	91
PRKCD	-0.058	0.26	0.34	10	-0.53	93	103
IL6R	0.032	0.028	-10000	0	-0.043	47	47
SOCS3	-0.042	0.22	-10000	0	-1	22	22
gp130 (dimer)/JAK1/JAK1/LMO4	0.042	0.088	-10000	0	-0.15	54	54
Rac1/GTP	-0.013	0.19	0.3	7	-0.39	68	75
HCK	0.037	0.014	-10000	0	0	65	65
MAPKKK cascade	-0.022	0.22	-10000	0	-0.51	67	67
bone resorption	-0.077	0.31	-10000	0	-0.72	78	78
IRF1	-0.14	0.42	-10000	0	-0.94	106	106
mol:GDP	-0.022	0.15	0.22	4	-0.37	58	62
SOS1	0.039	0.015	-10000	0	-0.001	53	53
VAV1	-0.022	0.15	0.22	4	-0.38	58	62
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.015	0.18	-10000	0	-0.51	48	48
PTPN11	0.001	0.16	-10000	0	-0.79	21	21
IL6/IL6RA	0.03	0.061	-10000	0	-0.13	41	41
gp130 (dimer)/TYK2/TYK2/LMO4	0.048	0.066	-10000	0	-0.11	46	46
gp130 (dimer)/JAK2/JAK2/LMO4	0.039	0.077	-10000	0	-0.13	60	60
IL6	0.023	0.036	-10000	0	-0.044	69	69
PIAS3	0.038	0.012	-10000	0	0	47	47
PTPRE	0.027	0.037	0.097	13	-0.043	66	79
PIAS1	0.039	0.008	-10000	0	0	24	24
RAC1	0.039	0.009	-10000	0	0	28	28
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.001	0.091	0.16	3	-0.23	43	46
LMO4	0.028	0.037	-10000	0	-0.044	68	68
STAT3 (dimer)/PIAS3	-0.099	0.39	-10000	0	-0.86	89	89
MCL1	0.004	0.16	-10000	0	-0.79	10	10

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0	0.11	0.15	67	-0.3	34	101
adherens junction organization	-0.017	0.12	0.19	8	-0.35	45	53
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.02	0.11	0.22	17	-0.28	27	44
FMN1	-0.012	0.11	0.15	9	-0.28	55	64
mol:IP3	0.009	0.096	0.16	69	-0.24	37	106
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.003	0.12	0.16	9	-0.29	59	68
CTNNB1	0.04	0.011	0.068	3	0	32	35
AKT1	-0.012	0.086	0.21	5	-0.27	35	40
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.002	0.14	-10000	0	-0.42	35	35
CTNND1	0.042	0.009	-10000	0	-0.002	18	18
mol:PI-4-5-P2	-0.005	0.12	0.22	21	-0.32	38	59
VASP	-0.013	0.11	0.16	5	-0.29	54	59
ZYX	-0.01	0.11	0.15	10	-0.3	44	54
JUB	-0.015	0.12	0.15	8	-0.29	57	65
EGFR(dimer)	0.004	0.13	-10000	0	-0.32	46	46
E-cadherin/beta catenin-gamma catenin	0.052	0.058	-10000	0	-0.11	45	45
mol:PI-3-4-5-P3	0.001	0.098	-10000	0	-0.27	37	37
PIK3CA	0.029	0.02	-10000	0	-0.001	169	169
PI3K	0.001	0.1	-10000	0	-0.28	37	37
FYN	-0.004	0.12	0.19	17	-0.28	58	75
mol:Ca2+	0.009	0.095	0.16	69	-0.23	37	106
JUP	0.038	0.013	0.068	1	0	57	58
PIK3R1	0.035	0.017	-10000	0	0	100	100
mol:DAG	0.009	0.096	0.16	69	-0.24	37	106
CDH1	0.036	0.015	-10000	0	0	79	79
RhoA/GDP	0.021	0.11	0.22	17	-0.28	28	45
establishment of polarity of embryonic epithelium	-0.011	0.11	0.18	8	-0.28	54	62
SRC	0.039	0.009	-10000	0	0	28	28
RAC1	0.039	0.009	-10000	0	0	28	28
RHOA	0.04	0.006	-10000	0	0	13	13
EGFR	0.036	0.014	-10000	0	0	67	67
CASR	0.003	0.094	0.16	76	-0.27	26	102
RhoA/GTP	0.023	0.1	0.2	11	-0.26	27	38
AKT2	-0.013	0.085	0.22	2	-0.27	34	36
actin cable formation	-0.016	0.11	0.24	8	-0.32	41	49
apoptosis	-0.007	0.11	0.28	37	-0.17	75	112
CTNNA1	0.04	0.011	-10000	0	-0.001	32	32
mol:GDP	0.002	0.1	0.17	72	-0.25	38	110
PIP5K1A	-0.013	0.11	0.15	5	-0.29	49	54
PLCG1	0.008	0.098	0.16	69	-0.24	37	106
Rac1/GTP	0.014	0.13	-10000	0	-0.31	43	43
homophilic cell adhesion	0.001	0.005	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.011	0.075	-10000	0	-0.14	101	101
CRKL	-0.024	0.13	0.28	3	-0.42	33	36
mol:PIP3	0.003	0.11	0.3	1	-0.83	8	9
AKT1	-0.003	0.1	0.37	2	-0.74	8	10
PTK2B	0.034	0.016	-10000	0	0	97	97
RAPGEF1	-0.028	0.13	0.26	3	-0.41	32	35
RANBP10	0.037	0.013	-10000	0	0	58	58
PIK3CA	0.029	0.019	-10000	0	0	166	166
HGF/MET/SHIP2	0.028	0.076	-10000	0	-0.12	100	100
MAP3K5	-0.014	0.13	0.27	1	-0.4	30	31
HGF/MET/CIN85/CBL/ENDOPHILINS	0.049	0.083	-10000	0	-0.11	101	101
AP1	-0.004	0.081	0.16	11	-0.14	102	113
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.039	0.008	-10000	0	0	23	23
apoptosis	-0.16	0.35	-10000	0	-0.76	130	130
STAT3 (dimer)	-0.006	0.11	0.19	5	-0.29	34	39
GAB1/CRKL/SHP2/PI3K	-0.006	0.14	-10000	0	-0.38	37	37
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	-0.004	0.14	0.29	2	-0.4	33	35
PTPN11	0.039	0.009	-10000	0	0	29	29
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.038	0.011	-10000	0	0	43	43
PTEN	0.038	0.01	-10000	0	0	36	36
ELK1	0.011	0.12	0.35	36	-10000	0	36
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.011	0.081	0.16	1	-0.23	37	38
PAK1	0.004	0.11	0.33	6	-0.68	8	14
HGF/MET/RANBP10	0.025	0.075	-10000	0	-0.11	101	101
HRAS	-0.072	0.21	-10000	0	-0.48	114	114
DOCK1	-0.029	0.13	0.25	7	-0.39	36	43
GAB1	-0.023	0.14	-10000	0	-0.44	33	33
CRK	-0.022	0.13	0.29	2	-0.42	32	34
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.054	0.19	-10000	0	-0.42	105	105
JUN	0.035	0.014	-10000	0	0	76	76
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.019	0.07	0.094	4	-0.16	100	104
PIK3R1	0.034	0.016	-10000	0	0	99	99
cell morphogenesis	0	0.15	0.27	35	-0.34	34	69
GRB2/SHC	0.018	0.094	-10000	0	-0.16	103	103
FOS	0.026	0.02	-10000	0	0	201	201
GLMN	0.005	0.006	0.068	5	-10000	0	5
cell motility	0.011	0.12	0.35	36	-10000	0	36
HGF/MET/MUC20	0.015	0.062	-10000	0	-0.11	102	102
cell migration	0.017	0.093	-10000	0	-0.16	103	103
GRB2	0.04	0.008	-10000	0	0	21	21
CBL	0.04	0.008	-10000	0	0	20	20
MET/RANBP10	0.011	0.073	-10000	0	-0.13	102	102
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.015	0.08	-10000	0	-0.18	79	79
MET/MUC20	-0.004	0.06	-10000	0	-0.12	104	104
RAP1B	-0.028	0.12	0.33	2	-0.38	29	31
RAP1A	-0.032	0.12	0.34	2	-0.39	33	35
HGF/MET/RANBP9	0.027	0.077	-10000	0	-0.12	99	99
RAF1	-0.07	0.21	-10000	0	-0.46	114	114
STAT3	-0.007	0.1	-10000	0	-0.29	33	33
cell proliferation	-0.03	0.14	0.26	10	-0.3	75	85
RPS6KB1	-0.01	0.082	-10000	0	-0.26	37	37
MAPK3	-0.008	0.12	0.62	12	-10000	0	12
MAPK1	0.021	0.18	0.71	31	-10000	0	31
RANBP9	0.038	0.012	-10000	0	0	47	47
MAPK8	-0.011	0.14	-10000	0	-0.4	38	38
SRC	-0.004	0.093	0.2	10	-0.27	26	36
PI3K	0.002	0.092	-10000	0	-0.18	87	87
MET/Glomulin	0.011	0.047	-10000	0	-0.12	45	45
SOS1	0.037	0.012	-10000	0	0	51	51
MAP2K1	-0.071	0.19	-10000	0	-0.43	114	114
MET	0.027	0.02	-10000	0	0	191	191
MAP4K1	-0.011	0.13	0.27	2	-0.44	28	30
PTK2	0.027	0.019	-10000	0	0	182	182
MAP2K2	-0.07	0.19	-10000	0	-0.42	115	115
BAD	-0.008	0.1	0.33	2	-0.71	8	10
MAP2K4	-0.016	0.12	0.26	1	-0.37	30	31
SHP2/GRB2/SOS1/GAB1	-0.009	0.15	-10000	0	-0.35	46	46
INPPL1	0.039	0.009	-10000	0	0	27	27
PXN	0.04	0.006	-10000	0	0	10	10
SH3KBP1	0.04	0.007	-10000	0	0	16	16
HGS	-0.026	0.071	0.082	4	-0.16	109	113
PLCgamma1/PKC	0.026	0.02	-10000	0	-0.12	8	8
HGF	0.039	0.009	-10000	0	0	27	27
RASA1	0.037	0.013	-10000	0	0	56	56
NCK1	0.036	0.014	-10000	0	0	70	70
PTPRJ	0.039	0.01	-10000	0	0	33	33
NCK/PLCgamma1	0.014	0.097	-10000	0	-0.17	100	100
PDPK1	-0.004	0.1	-10000	0	-0.77	8	8
HGF/MET/SHIP	0.015	0.062	-10000	0	-0.11	102	102

×

IL4-mediated signaling events

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
BCL2L1	-0.059	0.5	0.76	1	-1	69	70
STAT6 (cleaved dimer)	-0.1	0.45	-10000	0	-0.95	82	82
IGHG1	0.034	0.23	0.45	3	-0.72	7	10
IGHG3	-0.067	0.45	-10000	0	-0.94	75	75
AKT1	-0.055	0.37	-10000	0	-0.83	67	67
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.046	0.36	0.44	1	-0.86	67	68
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.051	0.4	-10000	0	-0.94	64	64
THY1	-0.22	0.66	-10000	0	-1.2	158	158
MYB	0.034	0.016	-10000	0	0	96	96
HMGA1	0.036	0.013	-10000	0	0	65	65
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.023	0.38	0.52	1	-0.76	66	67
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.055	0.4	-10000	0	-0.9	69	69
SP1	0.021	0.073	-10000	0	-0.12	102	102
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.001	0.05	-10000	0	-0.084	4	4
STAT6 (dimer)/ETS1	-0.082	0.46	-10000	0	-0.97	76	76
SOCS1	-0.026	0.34	-10000	0	-0.67	63	63
SOCS3	-0.038	0.37	0.58	2	-0.98	41	43
FCER2	-0.033	0.39	-10000	0	-0.82	51	51
PARP14	0.033	0.018	-10000	0	0	128	128
CCL17	-0.061	0.47	-10000	0	-1	62	62
GRB2	0.04	0.008	-10000	0	0	21	21
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.011	0.3	-10000	0	-0.65	59	59
T cell proliferation	-0.085	0.49	-10000	0	-1	80	80
IL4R/JAK1	-0.076	0.49	-10000	0	-1	77	77
EGR2	-0.057	0.48	-10000	0	-1	61	61
JAK2	0.031	0.071	0.18	2	-10000	0	2
JAK3	0.032	0.026	-10000	0	-0.041	32	32
PIK3R1	0.034	0.016	-10000	0	0	99	99
JAK1	0.04	0.041	0.11	3	-0.04	7	10
COL1A2	-0.16	0.57	-10000	0	-1.3	107	107
CCL26	-0.07	0.49	-10000	0	-1	71	71
IL4R	-0.066	0.52	-10000	0	-1.1	75	75
PTPN6	0.005	0.043	-10000	0	-0.08	2	2
IL13RA2	-0.059	0.47	-10000	0	-0.99	70	70
IL13RA1	0.035	0.074	0.18	6	-10000	0	6
IRF4	0.049	0.17	-10000	0	-0.92	5	5
ARG1	0.047	0.2	-10000	0	-0.78	4	4
CBL	-0.026	0.35	-10000	0	-0.71	66	66
GTF3A	0.013	0.079	-10000	0	-0.13	120	120
PIK3CA	0.029	0.019	-10000	0	0	166	166
IL13RA1/JAK2	0.039	0.12	0.25	4	-0.18	27	31
IRF4/BCL6	0.034	0.16	-10000	0	-0.87	5	5
CD40LG	0.048	0.008	-10000	0	-0.054	1	1
MAPK14	-0.032	0.37	0.62	1	-0.78	62	63
mitosis	-0.046	0.35	-10000	0	-0.77	67	67
STAT6	-0.063	0.54	0.76	2	-1.1	75	77
SPI1	0.044	0.01	-10000	0	-10000	0	0
RPS6KB1	-0.048	0.34	-10000	0	-0.74	67	67
STAT6 (dimer)	-0.06	0.54	0.76	2	-1.1	75	77
STAT6 (dimer)/PARP14	-0.1	0.49	-10000	0	-1	76	76
mast cell activation	-0.005	0.019	-10000	0	-0.044	9	9
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.074	0.39	-10000	0	-0.88	72	72
FRAP1	-0.055	0.37	-10000	0	-0.83	67	67
LTA	-0.06	0.47	-10000	0	-1	67	67
FES	0.04	0.008	-10000	0	0	22	22
T-helper 1 cell differentiation	0.055	0.53	1.1	75	-0.76	2	77
CCL11	-0.091	0.5	-10000	0	-1	84	84
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.049	0.39	-10000	0	-0.89	65	65
IL2RG	0.026	0.025	-10000	0	-0.047	12	12
IL10	-0.06	0.48	-10000	0	-1	63	63
IRS1	0.04	0.008	-10000	0	0	22	22
IRS2	0.039	0.009	-10000	0	0	30	30
IL4	0.042	0.22	-10000	0	-0.92	12	12
IL5	-0.061	0.47	-10000	0	-1.1	55	55
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.044	0.46	0.68	2	-0.9	78	80
COL1A1	-0.21	0.64	-10000	0	-1.3	136	136
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.082	0.49	-10000	0	-1.1	68	68
IL2R gamma/JAK3	0.02	0.073	-10000	0	-0.13	87	87
TFF3	-0.067	0.49	-10000	0	-1	70	70
ALOX15	-0.058	0.47	-10000	0	-1	67	67
MYBL1	0.036	0.014	-10000	0	0	70	70
T-helper 2 cell differentiation	-0.099	0.47	-10000	0	-0.95	86	86
SHC1	0.039	0.008	-10000	0	0	23	23
CEBPB	0.04	0.016	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.052	0.4	-10000	0	-0.89	69	69
mol:PI-3-4-5-P3	-0.054	0.37	-10000	0	-0.83	67	67
PI3K	-0.065	0.4	-10000	0	-0.91	67	67
DOK2	0.032	0.017	-10000	0	0	118	118
ETS1	0	0.046	-10000	0	-0.1	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.008	0.29	0.42	1	-0.63	60	61
ITGB3	-0.093	0.54	-10000	0	-1.1	83	83
PIGR	-0.057	0.49	-10000	0	-1.1	63	63
IGHE	-0.005	0.087	0.18	41	-0.19	23	64
MAPKKK cascade	-0.006	0.29	0.42	1	-0.62	60	61
BCL6	0.031	0.017	-10000	0	0	130	130
OPRM1	-0.062	0.47	-10000	0	-1	68	68
RETNLB	-0.055	0.48	-10000	0	-1	67	67
SELP	-0.057	0.48	-10000	0	-1	62	62
AICDA	-0.051	0.45	-10000	0	-0.96	65	65

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.031	0.018	-10000	0	0	137	137
ELF1	0.047	0.023	-10000	0	-0.26	2	2
CCNA2	0.032	0.017	-10000	0	0	122	122
PIK3CA	0.029	0.019	-10000	0	0	166	166
JAK3	0.037	0.013	-10000	0	-0.001	58	58
PIK3R1	0.034	0.016	-10000	0	0	100	100
JAK1	0.039	0.01	-10000	0	-0.001	34	34
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0	0.13	0.25	1	-0.34	37	38
SHC1	0.04	0.009	-10000	0	-0.001	24	24
SP1	0.042	0.042	-10000	0	-0.27	9	9
IL2RA	0.02	0.032	-10000	0	-0.49	2	2
IL2RB	0.036	0.015	-10000	0	0	77	77
SOS1	0.038	0.013	-10000	0	-0.001	53	53
IL2RG	0.028	0.02	-10000	0	0	180	180
G1/S transition of mitotic cell cycle	-0.036	0.18	0.27	5	-0.47	37	42
PTPN11	0.039	0.011	-10000	0	-0.003	32	32
CCND2	0.011	0.062	-10000	0	-0.49	8	8
LCK	0.039	0.01	-10000	0	-0.003	28	28
GRB2	0.04	0.009	-10000	0	-0.003	23	23
IL2	0.039	0.011	-10000	0	-0.002	36	36
CDK6	0.032	0.017	-10000	0	0	126	126
CCND3	0.004	0.14	0.39	1	-0.6	9	10

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.038	0.01	-9999	0	36	36
ITGB7	0.038	0.01	-9999	0	38	38
ITGA4	0.035	0.015	-9999	0	88	88
alpha4/beta7 Integrin	0.031	0.065	-9999	-0.14	66	66
alpha4/beta1 Integrin	0.031	0.065	-9999	-0.14	66	66

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.004	0.063	-10000	0	-10000	0	0
PLK1	-0.15	0.38	-10000	0	-0.95	72	72
CDKN1B	-0.041	0.2	0.43	2	-0.37	93	95
FOXO3	-0.13	0.35	-10000	0	-0.68	114	114
KAT2B	-0.008	0.028	0.041	2	-0.046	171	173
FOXO1/SIRT1	0.015	0.078	0.2	1	-0.22	19	20
CAT	-0.15	0.4	0.52	1	-0.97	78	79
CTNNB1	0.039	0.01	-10000	0	0	32	32
AKT1	0.013	0.055	-10000	0	-0.064	144	144
FOXO1	-0.004	0.071	0.21	2	-0.23	16	18
MAPK10	-0.001	0.045	0.19	4	-0.12	22	26
mol:GTP	0	0.003	-10000	0	-10000	0	0
FOXO4	-0.026	0.12	-10000	0	-0.3	59	59
response to oxidative stress	-0.006	0.029	-10000	0	-0.051	105	105
FOXO3A/SIRT1	-0.12	0.34	-10000	0	-0.55	170	170
XPO1	0.039	0.01	-10000	0	0	35	35
EP300	0.037	0.014	-10000	0	-10000	0	0
BCL2L11	0.011	0.11	-10000	0	-0.91	6	6
FOXO1/SKP2	0.011	0.076	-10000	0	-0.22	25	25
mol:GDP	-0.006	0.029	-10000	0	-0.051	105	105
RAN	0.04	0.008	-10000	0	0	21	21
GADD45A	-0.073	0.27	-10000	0	-0.78	51	51
YWHAQ	0.04	0.007	-10000	0	0	18	18
FOXO1/14-3-3 family	0.008	0.15	-10000	0	-0.4	41	41
MST1	0.011	0.055	-10000	0	-0.063	183	183
CSNK1D	0.039	0.008	-10000	0	0	24	24
CSNK1E	0.037	0.012	-10000	0	0	53	53
FOXO4/14-3-3 family	-0.002	0.15	-10000	0	-0.44	39	39
YWHAB	0.038	0.011	-10000	0	0	45	45
MAPK8	-0.001	0.047	0.19	5	-0.12	21	26
MAPK9	-0.003	0.048	0.19	5	-0.13	23	28
YWHAG	0.039	0.009	-10000	0	0	25	25
YWHAE	0.037	0.013	-10000	0	0	58	58
YWHAZ	0.034	0.016	-10000	0	0	96	96
SIRT1	0.037	0.018	0.11	2	-0.035	24	26
SOD2	-0.11	0.3	-10000	0	-0.66	94	94
RBL2	-0.12	0.33	-10000	0	-0.77	78	78
RAL/GDP	0.03	0.056	-10000	0	-0.1	41	41
CHUK	0.012	0.053	-10000	0	-0.063	165	165
Ran/GTP	0.026	0.019	-10000	0	-0.12	3	3
CSNK1G2	0.036	0.013	-10000	0	0	64	64
RAL/GTP	0.031	0.056	-10000	0	-0.092	48	48
CSNK1G1	0.04	0.007	-10000	0	0	16	16
FASLG	0.017	0.066	-10000	0	-1.2	1	1
SKP2	0.036	0.014	-10000	0	0	68	68
USP7	0.038	0.012	-10000	0	0	47	47
IKBKB	0.011	0.054	-10000	0	-0.062	171	171
CCNB1	-0.18	0.43	-10000	0	-1	92	92
FOXO1-3a-4/beta catenin	-0.057	0.2	-10000	0	-0.4	90	90
proteasomal ubiquitin-dependent protein catabolic process	0.011	0.075	-10000	0	-0.22	25	25
CSNK1A1	0.039	0.008	-10000	0	0	23	23
SGK1	-0.008	0.028	0.041	2	-0.046	171	173
CSNK1G3	0.039	0.01	-10000	0	0	31	31
Ran/GTP/Exportin 1	0.044	0.038	-10000	0	-0.1	27	27
ZFAND5	-0.02	0.1	-10000	0	-0.25	58	58
SFN	0.035	0.015	-10000	0	0	83	83
CDK2	0.039	0.013	-10000	0	-10000	0	0
FOXO3A/14-3-3	-0.01	0.16	-10000	0	-0.37	58	58
CREBBP	0.04	0.013	-10000	0	-10000	0	0
FBXO32	-0.2	0.54	-10000	0	-1.1	132	132
BCL6	-0.12	0.34	-10000	0	-0.94	58	58
RALB	0.039	0.009	-10000	0	0	25	25
RALA	0.04	0.008	-10000	0	0	19	19
YWHAH	0.038	0.011	-10000	0	0	46	46

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.036	0.014	-10000	0	0	68	68
GNB1/GNG2	0.01	0.12	-10000	0	-0.26	45	45
mol:DAG	-0.009	0.1	0.24	7	-0.25	42	49
PLCG1	-0.01	0.1	0.22	6	-0.25	43	49
YES1	-0.019	0.093	-10000	0	-0.26	43	43
FZD3	0.03	0.019	-10000	0	0	153	153
FZD6	0.029	0.019	-10000	0	0	162	162
G protein	0.021	0.12	0.24	30	-0.26	40	70
MAP3K7	-0.03	0.084	0.2	6	-0.22	43	49
mol:Ca2+	-0.009	0.1	0.24	7	-0.24	42	49
mol:IP3	-0.009	0.1	0.24	7	-0.25	42	49
NLK	-0.036	0.26	-10000	0	-0.82	54	54
GNB1	0.039	0.01	-10000	0	0	33	33
CAMK2A	-0.019	0.092	0.22	7	-0.24	41	48
MAP3K7IP1	0.037	0.012	-10000	0	0	51	51
Noncanonical Wnts/FZD	-0.017	0.093	-10000	0	-0.28	38	38
CSNK1A1	0.039	0.008	-10000	0	0	23	23
GNAS	-0.014	0.099	0.2	16	-0.27	39	55
GO:0007205	-0.016	0.096	0.23	7	-0.24	45	52
WNT6	0.04	0.006	-10000	0	0	13	13
WNT4	0.04	0.008	-10000	0	0	19	19
NFAT1/CK1 alpha	0	0.12	0.28	4	-0.28	38	42
GNG2	0.039	0.009	-10000	0	0	29	29
WNT5A	0.034	0.015	-10000	0	0	89	89
WNT11	0.032	0.017	-10000	0	0	118	118
CDC42	-0.023	0.091	-10000	0	-0.26	41	41

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.056	0.29	-10000	0	-0.85	61	61
oxygen homeostasis	0.004	0.012	0.034	19	-0.025	6	25
TCEB2	0.039	0.008	-10000	0	0	23	23
TCEB1	0.038	0.011	-10000	0	0	39	39
VHL/Elongin B/Elongin C/HIF2A	0.04	0.14	0.29	11	-0.22	61	72
EPO	0.028	0.18	0.35	13	-0.34	36	49
FIH (dimer)	0.039	0.025	0.087	3	-0.035	41	44
APEX1	0.032	0.033	-10000	0	-0.035	74	74
SERPINE1	0	0.16	0.35	14	-0.32	58	72
FLT1	-0.047	0.26	-10000	0	-0.7	68	68
ADORA2A	0.018	0.17	0.33	34	-0.31	53	87
germ cell development	0.017	0.18	0.34	30	-0.31	64	94
SLC11A2	0.022	0.19	0.34	28	-0.33	59	87
BHLHE40	0.01	0.17	0.33	21	-0.31	60	81
HIF1AN	0.039	0.025	0.087	3	-0.035	41	44
HIF2A/ARNT/SIRT1	0.038	0.15	0.31	12	-0.25	56	68
ETS1	0.042	0.025	0.12	1	-0.11	5	6
CITED2	0.018	0.13	-10000	0	-0.62	20	20
KDR	-0.04	0.25	-10000	0	-0.69	64	64
PGK1	0.023	0.19	0.35	30	-0.34	62	92
SIRT1	0.04	0.007	-10000	0	0	16	16
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	0.053	0.22	0.47	1	-0.35	56	57
EPAS1	0.006	0.11	0.22	21	-0.22	70	91
SP1	0.034	0.048	-10000	0	-0.11	52	52
ABCG2	0.022	0.18	0.35	26	-0.32	56	82
EFNA1	0.01	0.19	0.34	25	-0.35	69	94
FXN	0.018	0.17	0.33	33	-0.31	56	89
POU5F1	0.016	0.18	0.35	29	-0.32	64	93
neuron apoptosis	-0.051	0.21	0.34	56	-0.46	1	57
EP300	0.036	0.014	-10000	0	0	69	69
EGLN3	0.028	0.027	0.086	1	-0.034	23	24
EGLN2	0.038	0.024	0.088	3	-0.033	33	36
EGLN1	0.038	0.025	0.084	5	-0.035	40	45
VHL/Elongin B/Elongin C	0.069	0.038	-10000	0	-0.11	11	11
VHL	0.039	0.008	-10000	0	0	23	23
ARNT	0.032	0.032	-10000	0	-0.035	75	75
SLC2A1	-0.001	0.18	0.34	18	-0.33	67	85
TWIST1	0.017	0.17	0.33	34	-0.31	55	89
ELK1	0.046	0.013	-10000	0	-0.087	3	3
HIF2A/ARNT/Cbp/p300	0.038	0.16	0.33	13	-0.26	51	64
VEGFA	0.01	0.17	0.33	21	-0.31	60	81
CREBBP	0.037	0.012	-10000	0	0	53	53

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.01	0.15	0.24	14	-0.34	55	69
FYN	-0.032	0.18	0.26	13	-0.38	84	97
LAT/GRAP2/SLP76	-0.004	0.15	0.24	6	-0.33	66	72
IKBKB	0.038	0.011	-10000	0	0	41	41
AKT1	-0.016	0.14	0.22	10	-0.3	76	86
B2M	0.037	0.016	-10000	0	-0.004	66	66
IKBKG	-0.003	0.049	0.12	12	-0.1	56	68
MAP3K8	0.039	0.008	-10000	0	0	24	24
mol:Ca2+	-0.014	0.014	0.038	8	-0.043	43	51
integrin-mediated signaling pathway	0.044	0.035	-10000	0	-0.11	24	24
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.028	0.18	0.24	9	-0.41	77	86
TRPV6	0.076	0.33	1.3	37	-10000	0	37
CD28	0.041	0.007	-10000	0	0	13	13
SHC1	-0.014	0.16	0.23	18	-0.37	62	80
receptor internalization	-0.015	0.14	0.17	3	-0.34	69	72
PRF1	-0.01	0.2	-10000	0	-0.76	29	29
KRAS	0.034	0.016	-10000	0	0	95	95
GRB2	0.04	0.008	-10000	0	0	21	21
COT/AKT1	0.003	0.12	0.22	9	-0.25	74	83
LAT	-0.019	0.16	0.23	8	-0.36	67	75
EntrezGene:6955	0.001	0.003	-10000	0	-0.023	3	3
CD3D	0.034	0.018	-10000	0	-0.002	105	105
CD3E	0.036	0.016	-10000	0	-0.002	77	77
CD3G	0.032	0.019	-10000	0	-0.002	131	131
RASGRP2	0.009	0.019	0.074	1	-0.16	1	2
RASGRP1	-0.022	0.14	0.23	12	-0.31	82	94
HLA-A	0.038	0.015	-10000	0	-0.004	62	62
RASSF5	0.039	0.009	-10000	0	0	27	27
RAP1A/GTP/RAPL	0.045	0.036	-10000	0	-0.11	24	24
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.013	0.059	0.15	15	-0.11	43	58
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.02	0.064	-10000	0	-0.15	80	80
PRKCA	-0.008	0.081	0.19	11	-0.2	48	59
GRAP2	0.037	0.012	-10000	0	0	56	56
mol:IP3	-0.015	0.11	-10000	0	-0.26	64	64
EntrezGene:6957	0.001	0.004	-10000	0	-0.021	5	5
TCR/CD3/MHC I/CD8	-0.014	0.12	-10000	0	-0.38	41	41
ORAI1	-0.071	0.28	-10000	0	-1.1	37	37
CSK	-0.015	0.16	0.25	7	-0.38	61	68
B7 family/CD28	0.022	0.16	0.26	5	-0.34	66	71
CHUK	0.038	0.011	-10000	0	0	46	46
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.025	0.17	0.2	2	-0.37	75	77
PTPN6	-0.015	0.16	0.2	24	-0.35	69	93
VAV1	-0.018	0.16	0.22	12	-0.39	62	74
Monovalent TCR/CD3	-0.003	0.08	-10000	0	-0.21	60	60
CBL	0.04	0.008	-10000	0	0	20	20
LCK	-0.022	0.17	0.25	12	-0.38	72	84
PAG1	-0.013	0.16	0.21	29	-0.37	64	93
RAP1A	0.039	0.01	-10000	0	0	35	35
TCR/CD3/MHC I/CD8/LCK	-0.025	0.17	0.19	4	-0.37	77	81
CD80	0.039	0.01	-10000	0	0	32	32
CD86	0.034	0.016	-10000	0	0	99	99
PDK1/CARD11/BCL10/MALT1	-0.009	0.084	-10000	0	-0.18	76	76
HRAS	0.039	0.01	-10000	0	0	31	31
GO:0035030	-0.018	0.13	0.18	13	-0.3	67	80
CD8A	0.041	0.011	-10000	0	-0.018	16	16
CD8B	0.001	0.004	-10000	0	-0.021	6	6
PTPRC	0.025	0.02	-10000	0	0	222	222
PDK1/PKC theta	-0.024	0.15	0.24	10	-0.35	71	81
CSK/PAG1	-0.012	0.16	0.22	31	-0.38	57	88
SOS1	0.037	0.012	-10000	0	0	51	51
peptide-MHC class I	0.037	0.071	-10000	0	-0.17	50	50
GRAP2/SLP76	-0.002	0.17	0.25	4	-0.38	66	70
STIM1	-0.013	0.13	1.3	4	-10000	0	4
RAS family/GTP	0.008	0.077	0.18	6	-0.16	53	59
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.016	0.15	0.17	3	-0.35	69	72
mol:DAG	-0.027	0.089	-10000	0	-0.23	67	67
RAP1A/GDP	0.01	0.032	0.076	14	-0.057	47	61
PLCG1	0.038	0.011	-10000	0	0	43	43
CD247	0.001	0.003	-10000	0	-0.023	3	3
cytotoxic T cell degranulation	-0.008	0.2	-10000	0	-0.7	31	31
RAP1A/GTP	0.003	0.01	-10000	0	-0.034	18	18
mol:PI-3-4-5-P3	-0.02	0.16	0.22	11	-0.34	76	87
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.01	0.14	0.22	1	-0.32	64	65
NRAS	0.039	0.009	-10000	0	0	30	30
ZAP70	0.041	0.005	-10000	0	0	9	9
GRB2/SOS1	0.047	0.044	-10000	0	-0.14	24	24
LAT/GRAP2/SLP76/VAV1	-0.012	0.14	0.25	5	-0.34	63	68
MALT1	0.036	0.014	-10000	0	0	70	70
TRAF6	0.04	0.008	-10000	0	0	19	19
CD8 heterodimer	0.031	0.012	-10000	0	-0.038	8	8
CARD11	0.037	0.012	-10000	0	0	55	55
PRKCB	-0.027	0.061	-10000	0	-0.17	67	67
PRKCE	-0.006	0.085	0.2	16	-0.2	47	63
PRKCQ	-0.026	0.17	0.23	10	-0.39	73	83
LCP2	0.034	0.016	-10000	0	0	101	101
BCL10	0.041	0.005	-10000	0	0	8	8
regulation of survival gene product expression	-0.011	0.12	0.2	12	-0.26	77	89
IKK complex	0.003	0.049	0.14	15	-0.091	30	45
RAS family/GDP	-0.002	0.014	-10000	0	-0.034	44	44
MAP3K14	-0.003	0.091	0.16	13	-0.2	73	86
PDPK1	-0.018	0.13	0.22	11	-0.29	75	86
TCR/CD3/MHC I/CD8/Fyn	-0.037	0.19	-10000	0	-0.47	65	65

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	0.009	0.1	-10000	0	-0.13	145	145
SMAD6-7/SMURF1	0.071	0.037	-10000	0	-0.14	9	9
NOG	0.038	0.012	-10000	0	0	48	48
SMAD9	0.015	0.1	-10000	0	-0.41	25	25
SMAD4	0.038	0.011	-10000	0	0	43	43
SMAD5	-0.001	0.094	0.19	3	-0.27	34	37
BMP7/USAG1	-0.021	0.085	-10000	0	-0.16	137	137
SMAD5/SKI	0.014	0.1	-10000	0	-0.28	33	33
SMAD1	0.007	0.091	-10000	0	-0.31	26	26
BMP2	0.038	0.01	-10000	0	0	38	38
SMAD1/SMAD1/SMAD4	0.031	0.096	-10000	0	-0.29	26	26
BMPR1A	0.036	0.013	-10000	0	0	66	66
BMPR1B	0.031	0.018	-10000	0	0	138	138
BMPR1A-1B/BAMBI	0.008	0.087	-10000	0	-0.14	119	119
AHSG	0.034	0.016	-10000	0	0	101	101
CER1	0.038	0.011	-10000	0	0	41	41
BMP2-4/CER1	0.061	0.043	-10000	0	-0.12	12	12
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.009	0.1	0.18	1	-0.26	54	55
BMP2-4 (homodimer)	0.047	0.035	-10000	0	-0.13	12	12
RGMB	0.039	0.01	-10000	0	0	31	31
BMP6/BMPR2/BMPR1A-1B	0.049	0.086	-10000	0	-0.13	83	83
RGMA	0.039	0.009	-10000	0	0	29	29
SMURF1	0.04	0.006	-10000	0	0	13	13
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.001	0.078	-10000	0	-0.24	32	32
BMP2-4/USAG1	0.022	0.071	-10000	0	-0.12	78	78
SMAD6/SMURF1/SMAD5	0.013	0.11	-10000	0	-0.28	36	36
SOSTDC1	0.023	0.02	-10000	0	0	244	244
BMP7/BMPR2/BMPR1A-1B	0.007	0.1	-10000	0	-0.13	153	153
SKI	0.039	0.009	-10000	0	0	29	29
BMP6 (homodimer)	0.038	0.011	-10000	0	0	46	46
HFE2	0.038	0.01	-10000	0	0	36	36
ZFYVE16	0.035	0.014	-10000	0	0	78	78
MAP3K7	0.038	0.01	-10000	0	0	38	38
BMP2-4/CHRD	0.054	0.044	-10000	0	-0.12	8	8
SMAD5/SMAD5/SMAD4	0.012	0.1	-10000	0	-0.27	35	35
MAPK1	0.038	0.011	-10000	0	0	44	44
TAK1/TAB family	0.036	0.12	-10000	0	-0.24	37	37
BMP7 (homodimer)	0.022	0.021	-10000	0	0	260	260
NUP214	0.038	0.011	-10000	0	0	43	43
BMP6/FETUA	0.045	0.027	-10000	0	-10000	0	0
SMAD1/SKI	0.027	0.095	-10000	0	-0.3	27	27
SMAD6	0.039	0.008	-10000	0	0	24	24
CTDSP2	0.039	0.009	-10000	0	0	29	29
BMP2-4/FETUA	0.054	0.045	-10000	0	-0.12	10	10
MAP3K7IP1	0.037	0.012	-10000	0	0	51	51
GREM1	0.034	0.015	-10000	0	0	91	91
BMPR2 (homodimer)	0.039	0.01	-10000	0	0	31	31
GADD34/PP1CA	0.058	0.054	-10000	0	-0.12	35	35
BMPR1A-1B (homodimer)	0.017	0.077	-10000	0	-0.15	88	88
CHRDL1	0.026	0.02	-10000	0	0	207	207
ENDOFIN/SMAD1	0.023	0.095	-10000	0	-0.3	25	25
SMAD6-7/SMURF1/SMAD1	0.054	0.11	-10000	0	-0.35	17	17
SMAD6/SMURF1	0.04	0.006	-10000	0	0	13	13
BAMBI	0.028	0.019	-10000	0	0	170	170
SMURF2	0.039	0.009	-10000	0	0	28	28
BMP2-4/CHRDL1	0.02	0.076	-10000	0	-0.12	101	101
BMP2-4/GREM1	0.053	0.048	-10000	0	-0.12	17	17
SMAD7	0.038	0.01	-10000	0	0	36	36
SMAD8A/SMAD8A/SMAD4	0.03	0.11	-10000	0	-0.39	30	30
SMAD1/SMAD6	0.027	0.097	-10000	0	-0.3	26	26
TAK1/SMAD6	0.052	0.035	-10000	0	-0.13	15	15
BMP7	0.022	0.021	-10000	0	0	260	260
BMP6	0.038	0.011	-10000	0	0	46	46
MAP3K7IP2	0.037	0.012	-10000	0	0	53	53
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	0.002	0.082	-10000	0	-0.24	33	33
PPM1A	0.04	0.006	-10000	0	0	10	10
SMAD1/SMURF2	0.026	0.097	-10000	0	-0.31	24	24
SMAD7/SMURF1	0.054	0.028	-10000	0	-0.13	8	8
CTDSPL	0.04	0.007	-10000	0	0	15	15
PPP1CA	0.04	0.006	-10000	0	0	11	11
XIAP	0	0	-10000	0	-10000	0	0
CTDSP1	0.04	0.007	-10000	0	0	15	15
PPP1R15A	0.038	0.011	-10000	0	0	41	41
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	0.002	0.084	0.17	4	-0.25	31	35
CHRD	0.033	0.016	-10000	0	0	105	105
BMPR2	0.039	0.01	-10000	0	0	31	31
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.001	0.085	-10000	0	-0.26	31	31
BMP4	0.036	0.014	-10000	0	0	67	67
FST	0.033	0.017	-10000	0	0	111	111
BMP2-4/NOG	0.059	0.047	-10000	0	-0.12	19	19
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.016	0.11	-10000	0	-0.13	150	150

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.038	0.087	0.24	1	-0.14	65	66
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0.038	0.01	-10000	0	0	36	36
STAT1 (dimer)/Cbp/p300	0.006	0.12	0.27	10	-0.22	79	89
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.039	0.081	-10000	0	-0.15	67	67
antigen processing and presentation of peptide antigen via MHC class I	-0.024	0.094	-10000	0	-0.21	79	79
CaM/Ca2+	0.042	0.087	0.23	1	-0.14	64	65
RAP1A	0.039	0.01	-10000	0	0	35	35
STAT1 (dimer)/SHP2	0.001	0.095	0.22	10	-0.19	62	72
AKT1	0.017	0.11	0.22	54	-0.22	28	82
MAP2K1	-0.023	0.073	0.15	40	-0.18	34	74
MAP3K11	-0.016	0.078	0.17	43	-0.18	30	73
IFNGR1	0.034	0.022	0.08	1	-0.037	19	20
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	0.015	0.098	-10000	0	-0.29	36	36
Rap1/GTP	-0.044	0.058	0.066	4	-0.18	48	52
CRKL/C3G	0.055	0.019	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.062	0.09	-10000	0	-0.14	60	60
CEBPB	-0.02	0.16	0.29	2	-0.46	42	44
STAT3	0.038	0.011	-10000	0	0	41	41
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.043	0.16	-10000	0	-0.78	16	16
STAT1	-0.025	0.087	0.18	31	-0.21	47	78
CALM1	0.039	0.009	-10000	0	0	26	26
IFN-gamma (dimer)	0.03	0.027	0.08	1	-0.038	58	59
PIK3CA	0.029	0.019	-10000	0	0	166	166
STAT1 (dimer)/PIAS1	-0.007	0.097	0.23	14	-0.2	50	64
CEBPB/PTGES2/Cbp/p300	-0.007	0.12	-10000	0	-0.31	41	41
mol:Ca2+	0.034	0.085	0.23	1	-0.14	65	66
MAPK3	-0.014	0.13	-10000	0	-0.68	11	11
STAT1 (dimer)	-0.021	0.14	0.18	7	-0.28	78	85
MAPK1	-0.042	0.2	-10000	0	-0.76	31	31
JAK2	0.031	0.024	-10000	0	-0.036	30	30
PIK3R1	0.034	0.016	-10000	0	0	99	99
JAK1	0.035	0.024	0.08	1	-0.037	45	46
CAMK2D	0.036	0.014	-10000	0	0	69	69
DAPK1	-0.019	0.16	0.28	1	-0.49	44	45
SMAD7	0.001	0.075	0.16	43	-0.13	51	94
CBL/CRKL/C3G	0.029	0.09	0.24	15	-0.17	35	50
PI3K	0.019	0.09	-10000	0	-0.18	53	53
IFNG	0.03	0.027	0.08	1	-0.038	58	59
apoptosis	-0.007	0.14	0.26	2	-0.41	41	43
CAMK2G	0.04	0.008	-10000	0	0	21	21
STAT3 (dimer)	0.038	0.011	-10000	0	0	41	41
CAMK2A	0.04	0.006	-10000	0	0	12	12
CAMK2B	0.041	0.005	-10000	0	0	9	9
FRAP1	0.008	0.11	0.18	92	-0.21	32	124
PRKCD	0.013	0.12	0.23	49	-0.23	32	81
RAP1B	0.037	0.012	-10000	0	0	54	54
negative regulation of cell growth	-0.024	0.094	-10000	0	-0.21	79	79
PTPN2	0.04	0.008	-10000	0	0	19	19
EP300	0.036	0.014	-10000	0	0	69	69
IRF1	-0.045	0.1	0.21	6	-0.28	58	64
STAT1 (dimer)/PIASy	-0.024	0.093	0.19	32	-0.22	40	72
SOCS1	-0.002	0.19	-10000	0	-1.1	16	16
mol:GDP	0.026	0.085	0.22	15	-0.16	35	50
CASP1	-0.02	0.083	0.15	21	-0.16	98	119
PTGES2	0.04	0.008	-10000	0	0	22	22
IRF9	-0.005	0.052	0.11	15	-0.13	38	53
mol:PI-3-4-5-P3	0.005	0.08	-10000	0	-0.17	58	58
RAP1/GDP	0.016	0.09	0.2	4	-0.18	48	52
CBL	-0.016	0.078	0.17	44	-0.18	26	70
MAP3K1	-0.017	0.076	0.16	40	-0.18	30	70
PIAS1	0.039	0.008	-10000	0	0	24	24
PIAS4	0.037	0.012	-10000	0	0	54	54
antigen processing and presentation of peptide antigen via MHC class II	-0.024	0.094	-10000	0	-0.21	79	79
PTPN11	-0.011	0.078	0.17	42	-0.18	30	72
CREBBP	0.037	0.012	-10000	0	0	53	53
RAPGEF1	0.039	0.009	-10000	0	0	26	26

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.038	0.012	-10000	0	0	49	49
HDAC3	0.04	0.006	-10000	0	0	10	10
VDR	0.038	0.011	-10000	0	0	43	43
Cbp/p300/PCAF	0.039	0.043	-10000	0	-0.13	24	24
EP300	0.036	0.014	-10000	0	0	69	69
RARs/AIB1/Cbp/p300/PCAF/9cRA	-0.016	0.099	-10000	0	-0.26	56	56
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.04	0.008	-10000	0	0	20	20
AKT1	0.011	0.091	0.19	19	-0.21	28	47
RAR alpha/9cRA/Cyclin H	-0.006	0.12	-10000	0	-0.24	77	77
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.004	0.082	-10000	0	-0.21	54	54
CDC2	0.026	0.023	-10000	0	-0.005	186	186
response to UV	-0.001	0.008	-10000	0	-0.027	39	39
RAR alpha/Jnk1	0.015	0.068	-10000	0	-0.15	52	52
NCOR2	0.039	0.01	-10000	0	0	31	31
VDR/VDR/Vit D3	0.023	0.031	-10000	0	-0.12	22	22
RXRs/RARs/NRIP1/9cRA	-0.041	0.19	0.28	1	-0.45	77	78
NCOA2	0.037	0.013	-10000	0	0	60	60
NCOA3	0.035	0.015	-10000	0	0	84	84
NCOA1	0.04	0.008	-10000	0	0	22	22
VDR/VDR/DNA	0.038	0.011	-10000	0	0	43	43
RARG	0.035	0.021	-10000	0	-0.018	67	67
RAR gamma1/9cRA	0.041	0.033	-10000	0	-0.11	15	15
MAPK3	0.035	0.022	-10000	0	-0.025	60	60
MAPK1	0.038	0.011	-10000	0	0	44	44
MAPK8	0.034	0.024	-10000	0	-0.026	70	70
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.022	0.15	-10000	0	-0.31	95	95
RARA	0.006	0.054	-10000	0	-0.16	41	41
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.007	0.085	-10000	0	-0.22	55	55
PRKCA	0.03	0.032	-10000	0	-0.074	35	35
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.051	0.2	-10000	0	-0.5	74	74
RXRG	0.013	0.057	-10000	0	-0.18	34	34
RXRA	-0.028	0.098	-10000	0	-0.24	58	58
RXRB	0.011	0.059	-10000	0	-0.17	41	41
VDR/Vit D3/DNA	0.023	0.031	-10000	0	-0.12	22	22
RBP1	0.029	0.019	-10000	0	0	159	159
CRBP1/9-cic-RA	0.001	0.057	-10000	0	-0.12	91	91
RARB	0.031	0.026	-10000	0	-0.015	113	113
PRKCG	0.033	0.032	-10000	0	-0.072	41	41
MNAT1	0.04	0.007	-10000	0	0	18	18
RAR alpha/RXRs	-0.022	0.16	0.27	2	-0.35	84	86
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.014	0.13	0.24	2	-0.28	72	74
proteasomal ubiquitin-dependent protein catabolic process	-0.016	0.11	0.16	2	-0.26	58	60
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.05	0.2	-10000	0	-0.49	77	77
positive regulation of DNA binding	-0.012	0.11	-10000	0	-0.22	83	83
NRIP1	-0.084	0.31	-10000	0	-0.95	55	55
RXRs/RARs	-0.034	0.17	-10000	0	-0.39	83	83
RXRs/RXRs/DNA/9cRA	-0.037	0.14	-10000	0	-0.32	91	91
PRKACA	0.035	0.015	-10000	0	0	84	84
CDK7	0.035	0.015	-10000	0	0	84	84
TFIIH	0.061	0.052	-10000	0	-0.13	25	25
RAR alpha/9cRA	0.036	0.086	-10000	0	-0.19	27	27
CCNH	0.037	0.012	-10000	0	0	51	51
CREBBP	0.037	0.012	-10000	0	0	53	53
RAR gamma2/9cRA	0.046	0.06	-10000	0	-0.13	35	35

×

Plasma membrane estrogen receptor 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
GNB1/GNG2	0.064	0.064	-10000	0	-0.1	50	50
ER alpha/Gai/GDP/Gbeta gamma	-0.024	0.14	-10000	0	-0.3	77	77
AKT1	-0.086	0.26	-10000	0	-0.64	94	94
PIK3CA	0.029	0.019	-10000	0	0	166	166
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.085	0.27	-10000	0	-0.65	95	95
mol:Ca2+	-0.001	0.071	0.18	10	-0.28	24	34
IGF1R	0.033	0.017	-10000	0	0	112	112
E2/ER alpha (dimer)/Striatin	0.034	0.05	-10000	0	-0.11	51	51
SHC1	0.039	0.008	-10000	0	0	23	23
apoptosis	0.083	0.25	0.61	94	-10000	0	94
RhoA/GTP	0.014	0.047	-10000	0	-0.11	57	57
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.009	0.14	0.27	1	-0.29	69	70
regulation of stress fiber formation	0.015	0.069	0.16	16	-0.15	60	76
E2/ERA-ERB (dimer)	0.037	0.045	-10000	0	-0.11	42	42
KRAS	0.034	0.016	-10000	0	0	95	95
G13/GTP	0.033	0.045	-10000	0	-0.098	49	49
pseudopodium formation	-0.015	0.069	0.15	60	-0.16	16	76
E2/ER alpha (dimer)/PELP1	0.035	0.046	-10000	0	-0.11	42	42
GRB2	0.04	0.008	-10000	0	0	21	21
GNG2	0.039	0.009	-10000	0	0	29	29
GNAO1	0.035	0.015	-10000	0	0	85	85
HRAS	0.039	0.01	-10000	0	0	31	31
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.038	0.16	-10000	0	-0.38	79	79
E2/ER beta (dimer)	0.03	0.005	-10000	0	-10000	0	0
mol:GDP	-0.002	0.075	0.14	2	-0.23	46	48
mol:NADP	-0.038	0.16	-10000	0	-0.38	79	79
PIK3R1	0.034	0.016	-10000	0	0	99	99
mol:IP3	-0.003	0.071	0.18	7	-0.29	24	31
IGF-1R heterotetramer	0.033	0.017	-10000	0	0	112	112
PLCB1	0.004	0.068	-10000	0	-0.29	23	23
PLCB2	0.005	0.067	-10000	0	-0.28	25	25
IGF1	0.035	0.014	-10000	0	0	77	77
mol:L-citrulline	-0.038	0.16	-10000	0	-0.38	79	79
RHOA	0.04	0.006	-10000	0	0	13	13
Gai/GDP	-0.007	0.18	-10000	0	-0.59	44	44
JNK cascade	0.029	0.005	-10000	0	-10000	0	0
BCAR1	0.036	0.013	-10000	0	0	65	65
ESR2	0.04	0.007	-10000	0	0	15	15
GNAQ	0.038	0.012	-10000	0	0	48	48
ESR1	0.034	0.015	-10000	0	0	91	91
Gq family/GDP/Gbeta gamma	-0.048	0.24	-10000	0	-0.66	67	67
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.018	0.12	-10000	0	-0.66	11	11
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.008	0.14	0.26	2	-0.29	73	75
GNAZ	0.038	0.011	-10000	0	0	46	46
E2/ER alpha (dimer)	0.016	0.041	-10000	0	-0.12	42	42
STRN	0.039	0.008	-10000	0	0	23	23
GNAL	0.04	0.008	-10000	0	0	22	22
PELP1	0.038	0.011	-10000	0	0	39	39
MAPK11	0.013	0.008	0.069	1	-10000	0	1
GNAI2	0.04	0.006	-10000	0	0	13	13
GNAI3	0.038	0.011	-10000	0	0	45	45
GNAI1	0.034	0.015	-10000	0	0	93	93
HBEGF	-0.018	0.15	0.32	15	-0.33	57	72
cAMP biosynthetic process	0.031	0.038	-10000	0	-0.09	40	40
SRC	-0.024	0.14	0.22	17	-0.29	79	96
PI3K	0.023	0.06	-10000	0	-0.15	44	44
GNB1	0.039	0.01	-10000	0	0	33	33
G13/GDP/Gbeta gamma	0.04	0.091	-10000	0	-0.2	47	47
SOS1	0.037	0.012	-10000	0	0	51	51
IGF-1R heterotetramer/IGF1	-0.037	0.1	-10000	0	-0.25	74	74
Gs family/GTP	0.041	0.043	-10000	0	-0.091	40	40
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.054	0.049	-10000	0	-0.11	27	27
vasodilation	-0.035	0.16	-10000	0	-0.36	79	79
mol:DAG	-0.003	0.071	0.18	7	-0.29	24	31
Gs family/GDP/Gbeta gamma	0.005	0.078	-10000	0	-0.21	45	45
MSN	-0.016	0.072	0.15	60	-0.17	16	76
Gq family/GTP	0.018	0.072	-10000	0	-0.28	25	25
mol:PI-3-4-5-P3	-0.081	0.26	-10000	0	-0.62	96	96
NRAS	0.039	0.009	-10000	0	0	30	30
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.035	0.16	0.36	79	-10000	0	79
GRB2/SOS1	0.047	0.044	-10000	0	-0.14	24	24
RhoA/GDP	0.016	0.086	-10000	0	-0.22	49	49
NOS3	-0.04	0.17	-10000	0	-0.4	79	79
GNA11	0.037	0.013	-10000	0	0	61	61
MAPKKK cascade	-0.03	0.18	-10000	0	-0.46	74	74
E2/ER alpha (dimer)/PELP1/Src	-0.014	0.14	0.27	2	-0.3	76	78
ruffle organization	-0.015	0.069	0.15	60	-0.16	16	76
ROCK2	-0.009	0.079	0.17	67	-0.17	7	74
GNA14	0.039	0.009	-10000	0	0	29	29
GNA15	0.036	0.014	-10000	0	0	68	68
GNA13	0.039	0.008	-10000	0	0	23	23
MMP9	-0.02	0.15	0.36	15	-0.31	65	80
MMP2	-0.021	0.14	0.23	13	-0.32	57	70

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.001	0.07	0.14	13	-0.18	60	73
CRKL	0.038	0.01	-10000	0	0	36	36
Rac1/GDP	0.029	0.009	-10000	0	-0.12	1	1
DOCK1	0.037	0.012	-10000	0	0	53	53
ITGA4	0.035	0.015	-10000	0	0	88	88
alpha4/beta7 Integrin/MAdCAM1	0.063	0.074	-10000	0	-0.11	68	68
EPO	0.04	0.007	-10000	0	0	14	14
alpha4/beta7 Integrin	0.031	0.065	-10000	0	-0.14	66	66
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.038	0.012	-10000	0	0	49	49
alpha4/beta1 Integrin	0.031	0.065	-10000	0	-0.14	66	66
EPO/EPOR (dimer)	0.051	0.025	-10000	0	-0.13	2	2
lamellipodium assembly	0.021	0.11	-10000	0	-0.41	14	14
PIK3CA	0.029	0.019	-10000	0	0	166	166
PI3K	0.023	0.06	-10000	0	-0.15	44	44
ARF6	0.04	0.007	-10000	0	0	16	16
JAK2	0.002	0.075	-10000	0	-0.2	58	58
PXN	0.04	0.006	-10000	0	0	10	10
PIK3R1	0.034	0.016	-10000	0	0	99	99
MADCAM1	0.036	0.014	-10000	0	0	67	67
cell adhesion	0.061	0.072	-10000	0	-0.11	68	68
CRKL/CBL	0.055	0.02	-10000	0	-0.13	1	1
ITGB1	0.038	0.01	-10000	0	0	36	36
SRC	-0.019	0.091	0.2	23	-0.19	43	66
ITGB7	0.038	0.01	-10000	0	0	38	38
RAC1	0.039	0.009	-10000	0	0	28	28
alpha4/beta1 Integrin/VCAM1	-0.007	0.096	-10000	0	-0.14	154	154
p130Cas/Crk/Dock1	0.013	0.1	0.23	19	-0.18	45	64
VCAM1	0.02	0.021	-10000	0	0	281	281
RHOA	0.04	0.006	-10000	0	0	13	13
alpha4/beta1 Integrin/Paxillin/GIT1	0.069	0.073	-10000	0	-0.11	65	65
BCAR1	-0.018	0.081	0.2	20	-0.18	39	59
EPOR	0.036	0.014	-10000	0	0	74	74
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.04	0.008	-10000	0	0	20	20
GIT1	0.039	0.009	-10000	0	0	25	25
Rac1/GTP	0.02	0.11	-10000	0	-0.44	13	13

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.035	0.047	-10000	0	-0.11	43	43
cell-cell adhesion	0.042	0.041	0.17	13	-10000	0	13
Ephrin B/EPHB2/RasGAP	0.052	0.095	-10000	0	-0.12	97	97
ITSN1	0.04	0.007	-10000	0	0	15	15
PIK3CA	0.029	0.019	-10000	0	0	166	166
SHC1	0.039	0.008	-10000	0	0	23	23
Ephrin B1/EPHB3	0.037	0.037	-10000	0	-0.11	21	21
Ephrin B1/EPHB1	0.048	0.023	-10000	0	-0.11	5	5
HRAS/GDP	-0.019	0.11	0.19	1	-0.18	131	132
Ephrin B/EPHB1/GRB7	0.056	0.088	-10000	0	-0.11	84	84
Endophilin/SYNJ1	-0.025	0.059	0.19	11	-0.2	6	17
KRAS	0.034	0.016	-10000	0	0	95	95
Ephrin B/EPHB1/Src	0.059	0.087	-10000	0	-0.11	80	80
endothelial cell migration	0.02	0.074	-10000	0	-0.11	94	94
GRB2	0.04	0.008	-10000	0	0	21	21
GRB7	0.037	0.013	-10000	0	0	57	57
PAK1	-0.019	0.071	0.18	27	-0.19	11	38
HRAS	0.039	0.01	-10000	0	0	31	31
RRAS	-0.025	0.058	0.19	8	-0.19	11	19
DNM1	0.039	0.01	-10000	0	0	33	33
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.012	0.07	0.19	31	-0.17	4	35
lamellipodium assembly	-0.042	0.041	-10000	0	-0.17	13	13
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.004	0.071	-10000	0	-0.2	13	13
PIK3R1	0.034	0.016	-10000	0	0	99	99
EPHB2	0.038	0.01	-10000	0	0	38	38
EPHB3	0.032	0.017	-10000	0	0	126	126
EPHB1	0.037	0.012	-10000	0	0	50	50
EPHB4	0.039	0.008	-10000	0	0	23	23
mol:GDP	-0.043	0.095	0.19	9	-0.22	72	81
Ephrin B/EPHB2	0.045	0.079	-10000	0	-0.11	95	95
Ephrin B/EPHB3	0.035	0.075	-10000	0	-0.11	86	86
JNK cascade	-0.008	0.092	0.3	37	-0.18	2	39
Ephrin B/EPHB1	0.047	0.074	-10000	0	-0.11	83	83
RAP1/GDP	-0.028	0.12	0.33	2	-0.21	85	87
EFNB2	0.031	0.018	-10000	0	0	139	139
EFNB3	0.036	0.014	-10000	0	0	69	69
EFNB1	0.04	0.007	-10000	0	0	15	15
Ephrin B2/EPHB1-2	0.035	0.067	-10000	0	-0.11	78	78
RAP1B	0.037	0.012	-10000	0	0	54	54
RAP1A	0.039	0.01	-10000	0	0	35	35
CDC42/GTP	0.027	0.098	-10000	0	-0.16	82	82
Rap1/GTP	-0.046	0.05	0.06	3	-0.19	15	18
axon guidance	0.035	0.047	-10000	0	-0.11	43	43
MAPK3	-0.004	0.069	0.18	10	-0.22	8	18
MAPK1	-0.001	0.068	0.19	13	-0.21	8	21
Rac1/GDP	-0.032	0.11	0.28	4	-0.21	80	84
actin cytoskeleton reorganization	-0.053	0.06	-10000	0	-0.16	70	70
CDC42/GDP	-0.032	0.11	0.28	4	-0.22	78	82
PI3K	0.023	0.077	-10000	0	-0.12	94	94
EFNA5	0.034	0.015	-10000	0	0	93	93
Ephrin B2/EPHB4	0.023	0.06	-10000	0	-0.11	82	82
Ephrin B/EPHB2/Intersectin/N-WASP	0	0.08	-10000	0	-0.16	96	96
CDC42	0.04	0.007	-10000	0	0	18	18
RAS family/GTP	-0.041	0.048	-10000	0	-0.18	15	15
PTK2	0.14	0.26	0.56	146	-0.18	2	148
MAP4K4	-0.008	0.092	0.3	37	-0.18	2	39
SRC	0.039	0.009	-10000	0	0	28	28
KALRN	0.038	0.012	-10000	0	0	47	47
Intersectin/N-WASP	0.056	0.022	-10000	0	-0.13	5	5
neuron projection morphogenesis	-0.024	0.088	0.28	16	-0.21	16	32
MAP2K1	-0.003	0.064	0.17	1	-0.2	10	11
WASL	0.04	0.007	-10000	0	0	18	18
Ephrin B1/EPHB1-2/NCK1	0.076	0.063	-10000	0	-0.11	40	40
cell migration	-0.011	0.089	0.24	7	-0.24	13	20
NRAS	0.039	0.009	-10000	0	0	30	30
SYNJ1	-0.025	0.06	0.19	11	-0.2	6	17
PXN	0.04	0.006	-10000	0	0	10	10
TF	-0.029	0.054	0.17	10	-0.2	6	16
HRAS/GTP	0.031	0.079	-10000	0	-0.12	90	90
Ephrin B1/EPHB1-2	0.062	0.041	-10000	0	-0.11	17	17
cell adhesion mediated by integrin	0.009	0.062	0.17	9	-0.21	14	23
RAC1	0.039	0.009	-10000	0	0	28	28
mol:GTP	0.035	0.081	-10000	0	-0.12	92	92
RAC1-CDC42/GTP	-0.041	0.045	-10000	0	-0.2	8	8
RASA1	0.037	0.013	-10000	0	0	56	56
RAC1-CDC42/GDP	-0.021	0.11	0.29	4	-0.21	77	81
ruffle organization	-0.025	0.077	0.24	11	-0.24	2	13
NCK1	0.036	0.014	-10000	0	0	70	70
receptor internalization	-0.03	0.056	0.18	11	-0.19	8	19
Ephrin B/EPHB2/KALRN	0.056	0.092	-10000	0	-0.12	89	89
ROCK1	0.018	0.087	0.19	102	-10000	0	102
RAS family/GDP	-0.057	0.063	-10000	0	-0.16	107	107
Rac1/GTP	-0.042	0.046	-10000	0	-0.19	11	11
Ephrin B/EPHB1/Src/Paxillin	0.002	0.073	-10000	0	-0.15	83	83

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	-0.026	0.053	0.18	2	-0.21	33	35
RFC1	-0.025	0.056	0.18	4	-0.21	35	39
PRKDC	-0.019	0.069	0.21	18	-0.21	37	55
RIPK1	0.038	0.01	-10000	0	0	32	32
CASP7	0.006	0.11	-10000	0	-0.57	16	16
FASLG/FAS/FADD/FAF1	0.023	0.08	0.15	100	-0.17	37	137
MAP2K4	0.009	0.11	0.22	6	-0.33	29	35
mol:ceramide	0.017	0.091	-10000	0	-0.31	19	19
GSN	-0.026	0.051	0.13	1	-0.21	34	35
FASLG/FAS/FADD/FAF1/Caspase 8	0.024	0.087	0.19	9	-0.24	20	29
FAS	0.035	0.017	-10000	0	-0.002	93	93
BID	-0.03	0.018	0.23	1	-10000	0	1
MAP3K1	0.016	0.11	0.25	7	-0.36	22	29
MAP3K7	0.039	0.011	-10000	0	-0.001	39	39
RB1	-0.023	0.059	0.2	7	-0.2	32	39
CFLAR	0.039	0.008	-10000	0	0	19	19
HGF/MET	-0.013	0.091	-10000	0	-0.14	167	167
ARHGDIB	-0.015	0.073	0.21	24	-0.21	28	52
FADD	0.04	0.012	-10000	0	-0.009	26	26
actin filament polymerization	0.026	0.055	0.21	37	-10000	0	37
NFKB1	-0.035	0.22	-10000	0	-0.67	57	57
MAPK8	0.006	0.11	0.24	1	-0.37	24	25
DFFA	-0.024	0.055	0.18	4	-0.21	38	42
DNA fragmentation during apoptosis	-0.023	0.058	0.18	4	-0.21	39	43
FAS/FADD/MET	0.018	0.087	-10000	0	-0.13	124	124
CFLAR/RIP1	0.053	0.03	-10000	0	-0.15	8	8
FAIM3	0.04	0.007	-10000	0	0	15	15
FAF1	0.04	0.014	-10000	0	-0.01	33	33
PARP1	-0.021	0.063	0.22	13	-0.2	35	48
DFFB	-0.023	0.054	0.18	4	-0.21	36	40
CHUK	-0.042	0.21	-10000	0	-0.64	55	55
FASLG	0.04	0.013	-10000	0	-0.011	28	28
FAS/FADD	0.038	0.059	-10000	0	-0.13	52	52
HGF	0.039	0.009	-10000	0	0	27	27
LMNA	-0.018	0.066	0.21	15	-0.21	27	42
CASP6	-0.019	0.054	0.14	2	-0.22	23	25
CASP10	0.036	0.016	-10000	0	-0.004	72	72
CASP3	-0.02	0.059	0.16	2	-0.23	37	39
PTPN13	0.021	0.021	-10000	0	0	268	268
CASP8	-0.032	0.016	0.26	1	-10000	0	1
IL6	-0.026	0.23	-10000	0	-0.74	32	32
MET	0.027	0.02	-10000	0	0	191	191
ICAD/CAD	-0.026	0.054	0.19	5	-0.2	37	42
FASLG/FAS/FADD/FAF1/Caspase 10	0.017	0.092	-10000	0	-0.31	19	19
activation of caspase activity by cytochrome c	-0.03	0.018	0.23	1	-10000	0	1
PAK2	0.005	0.095	0.22	69	-0.21	32	101
BCL2	0.036	0.013	-10000	0	0	67	67

×

BCR signaling pathway

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
JUN	-0.043	0.14	0.3	1	-0.34	64	65
IKBKB	0.021	0.092	0.27	8	-0.28	13	21
AKT1	0.027	0.1	0.24	49	-0.19	14	63
IKBKG	0.021	0.076	0.22	3	-0.25	12	15
CALM1	-0.012	0.11	0.21	6	-0.34	37	43
PIK3CA	0.029	0.019	-10000	0	0	166	166
MAP3K1	-0.032	0.15	-10000	0	-0.42	44	44
MAP3K7	0.038	0.01	-10000	0	0	38	38
mol:Ca2+	-0.01	0.12	0.21	4	-0.34	43	47
DOK1	0.04	0.008	-10000	0	0	22	22
AP-1	-0.022	0.095	0.18	1	-0.22	61	62
LYN	0.035	0.015	-10000	0	0	83	83
BLNK	0.037	0.013	-10000	0	0	62	62
SHC1	0.039	0.008	-10000	0	0	23	23
BCR complex	0.052	0.025	-10000	0	-0.12	3	3
CD22	-0.016	0.094	-10000	0	-0.28	43	43
CAMK2G	-0.013	0.11	0.2	14	-0.32	39	53
CSNK2A1	0.038	0.012	-10000	0	0	47	47
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.02	0.062	-10000	0	-0.13	57	57
GO:0007205	-0.011	0.12	0.21	4	-0.34	45	49
SYK	0.036	0.014	-10000	0	0	67	67
ELK1	-0.015	0.12	0.22	3	-0.34	44	47
NFATC1	-0.033	0.11	0.21	2	-0.3	45	47
B-cell antigen/BCR complex	0.052	0.025	-10000	0	-0.12	3	3
PAG1/CSK	0.052	0.026	-10000	0	-0.13	4	4
NFKBIB	0.017	0.062	0.13	2	-0.13	64	66
HRAS	-0.011	0.1	0.22	4	-0.28	44	48
NFKBIA	0.019	0.057	0.13	2	-0.12	54	56
NF-kappa-B/RelA/I kappa B beta	0.024	0.055	0.12	5	-0.1	60	65
RasGAP/Csk	0.056	0.086	-10000	0	-0.11	83	83
mol:GDP	-0.011	0.12	0.2	4	-0.34	44	48
PTEN	0.039	0.01	-10000	0	0	36	36
CD79B	0.04	0.007	-10000	0	0	16	16
NF-kappa-B/RelA/I kappa B alpha	0.026	0.052	0.12	5	-0.1	52	57
GRB2	0.04	0.008	-10000	0	0	21	21
PI3K/BCAP/CD19	-0.026	0.15	-10000	0	-0.42	42	42
PIK3R1	0.034	0.016	-10000	0	0	99	99
mol:IP3	-0.006	0.12	0.21	4	-0.36	38	42
CSK	0.039	0.009	-10000	0	0	25	25
FOS	-0.015	0.12	0.22	7	-0.33	43	50
CHUK	0.001	0.11	0.22	3	-0.27	50	53
IBTK	0.036	0.013	-10000	0	0	64	64
CARD11/BCL10/MALT1/TAK1	0.014	0.12	-10000	0	-0.31	38	38
PTPN6	-0.01	0.095	0.18	24	-0.28	36	60
RELA	0.04	0.006	-10000	0	0	10	10
BCL2A1	0.016	0.042	0.098	2	-0.08	60	62
VAV2	-0.025	0.12	-10000	0	-0.33	52	52
ubiquitin-dependent protein catabolic process	0.02	0.06	-10000	0	-0.12	64	64
BTK	-0.038	0.25	-10000	0	-1.1	31	31
CD19	-0.019	0.1	-10000	0	-0.29	42	42
MAP4K1	0.036	0.014	-10000	0	0	67	67
CD72	0.04	0.006	-10000	0	0	12	12
PAG1	0.037	0.012	-10000	0	0	50	50
MAPK14	-0.029	0.14	0.31	3	-0.36	45	48
SH3BP5	0.04	0.008	-10000	0	0	22	22
PIK3AP1	-0.01	0.12	0.24	3	-0.39	34	37
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.015	0.16	-10000	0	-0.46	44	44
RAF1	-0.014	0.097	0.21	9	-0.28	40	49
RasGAP/p62DOK/SHIP	0.044	0.077	-10000	0	-0.1	89	89
CD79A	0.036	0.013	-10000	0	0	63	63
re-entry into mitotic cell cycle	-0.022	0.094	-10000	0	-0.22	59	59
RASA1	0.037	0.013	-10000	0	0	56	56
MAPK3	-0.019	0.087	0.22	8	-0.25	37	45
MAPK1	-0.017	0.088	0.23	10	-0.25	34	44
CD72/SHP1	0.023	0.12	0.29	20	-0.27	35	55
NFKB1	0.036	0.013	-10000	0	0	66	66
MAPK8	-0.031	0.13	-10000	0	-0.37	43	43
actin cytoskeleton organization	-0.026	0.11	0.25	3	-0.3	47	50
NF-kappa-B/RelA	0.04	0.12	-10000	0	-0.23	64	64
Calcineurin	0.013	0.12	0.28	1	-0.3	38	39
PI3K	-0.015	0.079	-10000	0	-0.25	26	26
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.001	0.12	0.22	4	-0.38	36	40
SOS1	0.037	0.012	-10000	0	0	51	51
Bam32/HPK1	-0.037	0.23	-10000	0	-0.69	46	46
DAPP1	-0.058	0.25	-10000	0	-0.77	49	49
cytokine secretion	-0.03	0.1	0.21	2	-0.29	45	47
mol:DAG	-0.006	0.12	0.21	4	-0.36	38	42
PLCG2	0.035	0.015	-10000	0	0	82	82
MAP2K1	-0.017	0.092	0.21	9	-0.27	37	46
B-cell antigen/BCR complex/FcgammaRIIB	0.037	0.07	-10000	0	-0.12	74	74
mol:PI-3-4-5-P3	0.015	0.1	0.23	43	-0.22	14	57
ETS1	-0.011	0.11	0.22	12	-0.32	36	48
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.068	0.082	-10000	0	-0.12	58	58
B-cell antigen/BCR complex/LYN	-0.014	0.1	-10000	0	-0.3	42	42
MALT1	0.036	0.014	-10000	0	0	70	70
TRAF6	0.04	0.008	-10000	0	0	19	19
RAC1	-0.027	0.12	0.26	3	-0.31	48	51
B-cell antigen/BCR complex/LYN/SYK	0.046	0.12	0.34	11	-0.25	22	33
CARD11	-0.012	0.12	0.22	5	-0.36	37	42
FCGR2B	0.03	0.019	-10000	0	0	153	153
PPP3CA	0.038	0.011	-10000	0	0	45	45
BCL10	0.041	0.005	-10000	0	0	8	8
IKK complex	0.02	0.051	0.15	19	-0.11	16	35
PTPRC	0.024	0.02	-10000	0	0	222	222
PDPK1	0.018	0.092	0.21	54	-0.17	12	66
PPP3CB	0.039	0.009	-10000	0	0	28	28
PPP3CC	0.033	0.016	-10000	0	0	103	103
POU2F2	0.016	0.042	0.12	8	-0.077	62	70

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	-0.025	0.2	-10000	0	-0.68	39	39
epithelial cell differentiation	-0.031	0.19	-10000	0	-0.61	42	42
ITCH	0.038	0.038	0.1	10	-0.094	30	40
WWP1	-0.061	0.28	0.32	1	-1.2	31	32
FYN	0.034	0.016	-10000	0	0	94	94
EGFR	0.036	0.014	-10000	0	0	67	67
PRL	0.039	0.01	-10000	0	0	31	31
neuron projection morphogenesis	-0.042	0.16	0.23	9	-0.56	35	44
PTPRZ1	0.039	0.01	-10000	0	0	32	32
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.005	0.18	-10000	0	-0.61	35	35
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.033	0.18	-10000	0	-0.65	37	37
ADAM17	0.037	0.035	0.097	6	-0.08	30	36
ErbB4/ErbB4	-0.05	0.21	-10000	0	-0.84	32	32
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.03	0.2	-10000	0	-0.65	41	41
NCOR1	0.037	0.013	-10000	0	0	58	58
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.026	0.18	-10000	0	-0.6	40	40
GRIN2B	-0.034	0.16	0.24	3	-0.56	40	43
ErbB4/ErbB2/betacellulin	-0.025	0.18	-10000	0	-0.55	46	46
STAT1	0.034	0.016	-10000	0	0	102	102
HBEGF	0.039	0.009	-10000	0	0	27	27
PRLR	0.035	0.015	-10000	0	0	80	80
E4ICDs/ETO2	-0.029	0.2	-10000	0	-0.68	39	39
axon guidance	-0.054	0.22	-10000	0	-0.76	41	41
NEDD4	0.036	0.039	0.1	7	-0.082	39	46
Prolactin receptor/Prolactin receptor/Prolactin	0.05	0.024	-10000	0	-10000	0	0
CBFA2T3	0.035	0.015	-10000	0	0	82	82
ErbB4/ErbB2/HBEGF	-0.018	0.18	-10000	0	-0.57	43	43
MAPK3	-0.024	0.16	0.28	4	-0.58	35	39
STAT1 (dimer)	-0.034	0.21	-10000	0	-0.52	60	60
MAPK1	-0.024	0.16	0.26	6	-0.58	35	41
JAK2	0.034	0.016	-10000	0	0	101	101
ErbB4/ErbB2/neuregulin 1 beta	-0.03	0.17	0.19	2	-0.64	36	38
NRG1	-0.007	0.032	0.035	111	-0.11	21	132
NRG3	0.034	0.015	-10000	0	0	91	91
NRG2	0.041	0.005	-10000	0	0	8	8
NRG4	0.028	0.019	-10000	0	0	169	169
heart development	-0.054	0.22	-10000	0	-0.76	41	41
neural crest cell migration	-0.029	0.17	0.19	2	-0.63	36	38
ERBB2	-0.009	0.032	0.035	111	-0.098	25	136
WWOX/E4ICDs	-0.029	0.2	-10000	0	-0.69	37	37
SHC1	0.039	0.008	-10000	0	0	23	23
ErbB4/EGFR/neuregulin 4	-0.036	0.2	-10000	0	-0.68	38	38
apoptosis	0.03	0.19	0.63	43	-10000	0	43
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.024	0.21	-10000	0	-0.68	39	39
ErbB4/ErbB2/epiregulin	-0.018	0.18	-10000	0	-0.57	42	42
ErbB4/ErbB4/betacellulin/betacellulin	-0.034	0.2	-10000	0	-0.61	47	47
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.005	0.2	-10000	0	-0.63	36	36
MDM2	-0.042	0.19	0.27	11	-0.72	33	44
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.02	0.16	-10000	0	-0.57	37	37
STAT5A	-0.058	0.22	0.24	1	-0.73	42	43
ErbB4/EGFR/neuregulin 1 beta	-0.025	0.18	-10000	0	-0.63	37	37
DLG4	0.038	0.01	-10000	0	0	38	38
GRB2/SHC	0.055	0.022	-10000	0	-0.13	4	4
E4ICDs/TAB2/NCoR1	-0.019	0.21	-10000	0	-0.65	41	41
STAT5A (dimer)	-0.025	0.22	-10000	0	-0.68	42	42
MAP3K7IP2	0.037	0.012	-10000	0	0	53	53
STAT5B (dimer)	-0.037	0.23	-10000	0	-0.74	42	42
LRIG1	0.033	0.017	-10000	0	0	112	112
EREG	0.038	0.011	-10000	0	0	42	42
BTC	0.033	0.016	-10000	0	0	105	105
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.058	0.23	-10000	0	-0.77	41	41
ERBB4	-0.049	0.2	-10000	0	-0.84	31	31
STAT5B	0.039	0.009	-10000	0	0	27	27
YAP1	0.002	0.094	-10000	0	-0.54	14	14
GRB2	0.04	0.008	-10000	0	0	21	21
ErbB4/ErbB2/neuregulin 4	-0.03	0.18	-10000	0	-0.62	38	38
glial cell differentiation	0.019	0.2	0.64	41	-10000	0	41
WWOX	0.029	0.019	-10000	0	0	156	156
cell proliferation	-0.068	0.22	0.28	1	-0.6	58	59

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.032	0.14	-10000	0	-0.34	80	80
KLHL20	-0.015	0.1	0.21	12	-0.23	53	65
CYFIP2	0.038	0.011	-10000	0	0	45	45
Rac1/GDP	-0.007	0.11	0.26	8	-0.25	45	53
ENAH	-0.029	0.14	-10000	0	-0.35	74	74
AP1M1	0.036	0.014	-10000	0	0	72	72
RAP1B	0.037	0.012	-10000	0	0	54	54
RAP1A	0.039	0.01	-10000	0	0	35	35
CTNNB1	0.039	0.01	-10000	0	0	32	32
CDC42/GTP	0.005	0.077	0.16	2	-0.2	31	33
ABI1/Sra1/Nap1	-0.033	0.055	-10000	0	-0.15	69	69
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.068	0.067	-10000	0	-0.11	43	43
RAPGEF1	-0.027	0.12	0.27	4	-0.31	68	72
CTNND1	0.04	0.007	-10000	0	0	17	17
regulation of calcium-dependent cell-cell adhesion	-0.019	0.14	-10000	0	-0.35	78	78
CRK	-0.023	0.13	0.25	1	-0.34	64	65
E-cadherin/gamma catenin/alpha catenin	0.053	0.063	-10000	0	-0.14	41	41
alphaE/beta7 Integrin	0.048	0.038	-10000	0	-0.13	17	17
IQGAP1	0.036	0.013	-10000	0	0	66	66
NCKAP1	0.039	0.009	-10000	0	0	26	26
Rap1/GTP/I-afadin	0.043	0.063	-10000	0	-0.11	61	61
DLG1	-0.027	0.13	-10000	0	-0.35	63	63
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.028	0.044	-10000	0	-0.15	40	40
MLLT4	0.033	0.016	-10000	0	0	109	109
ARF6/GTP/NME1/Tiam1	0.047	0.062	-10000	0	-0.11	61	61
PI3K	-0.034	0.058	-10000	0	-0.19	40	40
ARF6	0.04	0.007	-10000	0	0	16	16
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.04	0.051	-10000	0	-0.15	30	30
TIAM1	0.036	0.013	-10000	0	0	66	66
E-cadherin(dimer)/Ca2+	0.065	0.069	-10000	0	-0.12	48	48
AKT1	0.009	0.076	0.16	65	-0.16	16	81
PIK3R1	0.034	0.016	-10000	0	0	99	99
CDH1	0.035	0.015	-10000	0	0	79	79
RhoA/GDP	-0.009	0.11	0.25	4	-0.25	48	52
actin cytoskeleton organization	-0.009	0.078	0.17	12	-0.17	52	64
CDC42/GDP	-0.007	0.11	0.27	6	-0.25	45	51
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.001	0.075	-10000	0	-0.2	56	56
ITGB7	0.038	0.01	-10000	0	0	38	38
RAC1	0.039	0.009	-10000	0	0	28	28
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.07	0.074	-10000	0	-0.13	48	48
E-cadherin/Ca2+/beta catenin/alpha catenin	0.048	0.053	-10000	0	-0.1	45	45
mol:GDP	-0.026	0.11	0.25	8	-0.28	48	56
CDC42/GTP/IQGAP1	0.039	0.046	-10000	0	-0.11	42	42
JUP	0.037	0.013	-10000	0	0	57	57
p120 catenin/RhoA/GDP	0.003	0.11	0.26	4	-0.26	44	48
RAC1/GTP/IQGAP1	0.039	0.045	-10000	0	-0.11	40	40
PIP5K1C/AP1M1	0.048	0.026	-10000	0	-0.13	1	1
RHOA	0.04	0.006	-10000	0	0	13	13
CDC42	0.04	0.007	-10000	0	0	18	18
CTNNA1	0.039	0.01	-10000	0	0	31	31
positive regulation of S phase of mitotic cell cycle	-0.016	0.058	0.1	4	-0.12	103	107
NME1	0.036	0.014	-10000	0	0	71	71
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.03	0.14	-10000	0	-0.36	72	72
regulation of cell-cell adhesion	-0.009	0.06	-10000	0	-0.15	47	47
WASF2	-0.007	0.043	0.11	13	-0.092	50	63
Rap1/GTP	0.004	0.084	0.19	18	-0.23	26	44
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.073	0.081	-10000	0	-0.12	48	48
CCND1	-0.02	0.071	0.12	2	-0.14	105	107
VAV2	-0.047	0.22	-10000	0	-0.6	56	56
RAP1/GDP	0.004	0.095	0.22	9	-0.26	26	35
adherens junction assembly	-0.031	0.14	-10000	0	-0.34	75	75
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.039	0.009	-10000	0	0	28	28
PIP5K1C	0.037	0.012	-10000	0	0	51	51
regulation of heterotypic cell-cell adhesion	0.045	0.073	0.22	2	-0.12	60	62
E-cadherin/beta catenin	0.007	0.04	0.14	1	-0.23	12	13
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.031	0.14	-10000	0	-0.34	77	77
PIK3CA	0.029	0.019	-10000	0	0	166	166
Rac1/GTP	-0.056	0.13	-10000	0	-0.35	66	66
E-cadherin/beta catenin/alpha catenin	0.055	0.062	-10000	0	-0.13	45	45
ITGAE	0.038	0.011	-10000	0	0	41	41
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.02	0.15	-10000	0	-0.35	78	78

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.052	0.063	-9999	-0.12	47	47
E-cadherin/beta catenin	0.041	0.049	-9999	-0.14	33	33
CTNNB1	0.039	0.01	-9999	0	32	32
JUP	0.037	0.013	-9999	0	57	57
CDH1	0.035	0.014	-9999	0	79	79

×

Caspase cascade in apoptosis

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
TOP1	-0.011	0.14	0.28	2	-0.3	65	67
ACTA1	0.005	0.085	0.2	14	-0.23	21	35
NUMA1	-0.014	0.13	0.25	3	-0.3	71	74
SPTAN1	-0.002	0.083	0.19	11	-0.23	20	31
LIMK1	0.002	0.084	0.2	13	-0.23	21	34
BIRC3	0.025	0.02	-10000	0	0	210	210
BIRC2	0.036	0.014	-10000	0	0	72	72
BAX	0.039	0.008	-10000	0	0	23	23
CASP10	-0.011	0.025	0.059	54	-10000	0	54
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	-0.031	0.17	0.28	2	-0.38	70	72
DIABLO	0.037	0.013	-10000	0	0	61	61
apoptotic nuclear changes	-0.002	0.082	0.19	11	-0.23	20	31
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.04	0.006	-10000	0	0	10	10
GSN	-0.002	0.083	0.2	12	-0.24	20	32
MADD	0.041	0.005	-10000	0	0	9	9
TFAP2A	-0.028	0.2	-10000	0	-0.56	51	51
BID	0.002	0.022	-10000	0	-0.094	22	22
MAP3K1	-0.018	0.13	-10000	0	-0.37	56	56
TRADD	0.037	0.013	-10000	0	0	61	61
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.051	0.039	-10000	0	-0.14	18	18
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.007	0.1	0.23	42	-0.22	33	75
CASP9	0.039	0.008	-10000	0	0	24	24
DNA repair	-0.012	0.08	0.27	23	-0.16	11	34
neuron apoptosis	-0.03	0.19	-10000	0	-0.63	43	43
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.013	0.12	0.23	6	-0.3	45	51
APAF1	0.039	0.009	-10000	0	0	28	28
CASP6	-0.094	0.33	-10000	0	-0.86	80	80
TRAF2	0.039	0.01	-10000	0	0	32	32
ICAD/CAD	-0.002	0.079	0.2	11	-0.22	18	29
CASP7	0.016	0.097	0.18	79	-0.25	17	96
KRT18	-0.012	0.14	-10000	0	-0.57	22	22
apoptosis	-0.036	0.16	0.29	11	-0.37	77	88
DFFA	0.002	0.081	0.2	11	-0.22	19	30
DFFB	0.002	0.082	0.2	11	-0.23	20	31
PARP1	0.012	0.08	0.16	11	-0.28	23	34
actin filament polymerization	0.003	0.081	0.23	18	-0.23	10	28
TNF	0.04	0.008	-10000	0	0	22	22
CYCS	-0.001	0.067	0.15	9	-0.21	31	40
SATB1	-0.097	0.31	-10000	0	-0.82	79	79
SLK	-0.001	0.085	0.22	9	-0.23	22	31
p15 BID/BAX	0.025	0.058	0.18	2	-0.13	38	40
CASP2	0	0.091	0.23	18	-0.24	35	53
JNK cascade	0.018	0.13	0.37	56	-10000	0	56
CASP3	0.007	0.087	0.18	26	-0.21	27	53
LMNB2	-0.047	0.21	0.24	2	-0.41	102	104
RIPK1	0.039	0.01	-10000	0	0	32	32
CASP4	0.033	0.016	-10000	0	0	107	107
Mammalian IAPs/DIABLO	0.011	0.088	-10000	0	-0.13	129	129
negative regulation of DNA binding	-0.027	0.19	-10000	0	-0.55	51	51
stress fiber formation	-0.001	0.084	0.22	9	-0.22	22	31
GZMB	-0.016	0.009	0	125	-10000	0	125
CASP1	-0.012	0.069	-10000	0	-0.2	66	66
LMNB1	-0.046	0.19	0.25	4	-0.35	115	119
APP	-0.031	0.2	-10000	0	-0.64	43	43
TNFRSF1A	0.036	0.014	-10000	0	0	72	72
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.01	0.002	0	27	-10000	0	27
VIM	-0.03	0.16	0.29	11	-0.36	81	92
LMNA	-0.018	0.15	0.29	1	-0.37	58	59
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.002	0.086	-10000	0	-0.24	39	39
LRDD	0.039	0.01	-10000	0	0	36	36
SREBF1	0.002	0.082	0.2	10	-0.23	21	31
APAF-1/Caspase 9	0.027	0.16	-10000	0	-0.69	20	20
nuclear fragmentation during apoptosis	-0.013	0.13	0.25	3	-0.29	71	74
CFL2	-0.003	0.081	0.23	10	-0.23	18	28
GAS2	0.004	0.086	0.21	17	-0.23	21	38
positive regulation of apoptosis	-0.04	0.18	0.24	3	-0.4	88	91
PRF1	0.037	0.013	-10000	0	0	61	61

×

Signaling events mediated by PRL

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
CCNE1	0.026	0.02	-10000	0	0	202	202
mol:Halofuginone	0.002	0.022	-10000	0	-0.17	9	9
ITGA1	0.032	0.017	-10000	0	0	121	121
CDKN1A	0.021	0.077	-10000	0	-0.35	16	16
PRL-3/alpha Tubulin	0.011	0.038	-10000	0	-0.12	35	35
mol:Ca2+	-0.004	0.072	0.26	35	-10000	0	35
AGT	0.039	0.01	-10000	0	0	35	35
CCNA2	-0.015	0.09	-10000	0	-0.61	7	7
TUBA1B	0	0	-10000	0	-10000	0	0
EGR1	0.006	0.043	-10000	0	-0.32	9	9
CDK2/Cyclin E1	0.023	0.092	-10000	0	-0.36	16	16
MAPK3	-0.012	0.01	0	221	-10000	0	221
PRL-2 /Rab GGTase beta	0.032	0.067	-10000	0	-0.14	70	70
MAPK1	-0.012	0.01	-10000	0	-10000	0	0
PTP4A1	-0.004	0.074	-10000	0	-0.61	7	7
PTP4A3	0.025	0.02	-10000	0	0	209	209
PTP4A2	0.039	0.009	-10000	0	0	30	30
ITGB1	-0.012	0.01	-10000	0	-10000	0	0
SRC	0.039	0.009	-10000	0	0	28	28
RAC1	-0.006	0.11	-10000	0	-0.36	42	42
Rab GGTase beta/Rab GGTase alpha	0.035	0.062	-10000	0	-0.13	62	62
PRL-1/ATF-5	0.017	0.097	0.26	2	-0.54	9	11
RABGGTA	0.04	0.007	-10000	0	0	17	17
BCAR1	-0.005	0.066	0.26	29	-10000	0	29
RHOC	-0.005	0.11	-10000	0	-0.37	40	40
RHOA	-0.006	0.11	-10000	0	-0.36	42	42
cell motility	0.008	0.12	-10000	0	-0.34	43	43
PRL-1/alpha Tubulin	-0.017	0.078	-10000	0	-0.53	9	9
PRL-3/alpha1 Integrin	0.01	0.067	-10000	0	-0.14	69	69
ROCK1	0.008	0.12	-10000	0	-0.34	42	42
RABGGTB	0.035	0.014	-10000	0	0	79	79
CDK2	0.037	0.013	-10000	0	0	56	56
mitosis	-0.001	0.077	0.2	6	-0.6	7	13
ATF5	0.038	0.011	-10000	0	0	41	41

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.022	0.14	-10000	0	-0.43	44	44
HDAC1	0.043	0.024	0.083	111	-0.003	54	165
AES	0.038	0.016	0.078	17	0	69	86
FBXW11	0.04	0.008	-10000	0	0	22	22
DTX1	0.041	0.005	-10000	0	0	9	9
LRP6/FZD1	0.042	0.048	-10000	0	-0.13	32	32
TLE1	0.039	0.014	0.076	14	-0.001	51	65
AP1	-0.007	0.082	0.14	2	-0.18	87	89
NCSTN	0.039	0.008	-10000	0	0	22	22
ADAM10	0.039	0.01	-10000	0	0	31	31
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.074	0.22	-10000	0	-0.65	49	49
NICD/RBPSUH	-0.006	0.13	-10000	0	-0.44	43	43
WIF1	0.039	0.009	-10000	0	0	26	26
NOTCH1	0.006	0.13	-10000	0	-0.46	39	39
PSENEN	0.034	0.016	-10000	0	0	96	96
KREMEN2	0.039	0.009	-10000	0	0	29	29
DKK1	0.038	0.011	-10000	0	0	39	39
beta catenin/beta TrCP1	0.015	0.093	0.23	1	-0.3	19	20
APH1B	0.035	0.014	-10000	0	0	79	79
APH1A	0.038	0.011	-10000	0	0	42	42
AXIN1	-0.016	0.12	0.23	1	-0.45	28	29
CtBP/CBP/TCF1/TLE1/AES	0.009	0.099	0.18	82	-0.18	51	133
PSEN1	0.039	0.01	-10000	0	0	31	31
FOS	0.026	0.02	-10000	0	0	201	201
JUN	0.035	0.014	-10000	0	0	76	76
MAP3K7	0.041	0.014	0.068	14	0	38	52
CTNNB1	-0.001	0.086	0.22	1	-0.31	17	18
MAPK3	0.04	0.007	-10000	0	0	18	18
DKK2/LRP6/Kremen 2	0.057	0.053	-10000	0	-0.12	29	29
HNF1A	0.002	0.008	0.037	18	-10000	0	18
CTBP1	0.04	0.015	0.078	19	0	49	68
MYC	-0.15	0.41	-10000	0	-1.2	69	69
NKD1	0.039	0.012	-10000	0	0	43	43
FZD1	0.04	0.006	-10000	0	0	13	13
NOTCH1 precursor/Deltex homolog 1	0.024	0.15	-10000	0	-0.43	45	45
apoptosis	-0.007	0.082	0.14	2	-0.18	87	89
Delta 1/NOTCHprecursor	0.019	0.14	-10000	0	-0.42	46	46
DLL1	0.037	0.013	-10000	0	0	61	61
PPARD	0.009	0.069	-10000	0	-0.87	2	2
Gamma Secretase	0.066	0.084	-10000	0	-0.12	63	63
APC	-0.015	0.12	0.23	1	-0.46	28	29
DVL1	0.012	0.068	-10000	0	-0.26	24	24
CSNK2A1	0.037	0.012	-10000	0	0	47	47
MAP3K7IP1	0.04	0.015	0.068	15	0	51	66
DKK1/LRP6/Kremen 2	0.056	0.052	-10000	0	-0.12	28	28
LRP6	0.034	0.016	-10000	0	0	94	94
CSNK1A1	0.039	0.008	-10000	0	0	23	23
NLK	0.026	0.042	-10000	0	-0.22	11	11
CCND1	-0.16	0.44	-10000	0	-1.2	81	81
WNT1	0.04	0.006	-10000	0	0	10	10
Axin1/APC/beta catenin	-0.002	0.12	0.27	2	-0.37	26	28
DKK2	0.039	0.01	-10000	0	0	33	33
NOTCH1 precursor/DVL1	0.013	0.15	-10000	0	-0.43	44	44
GSK3B	0.04	0.009	-10000	0	0	23	23
FRAT1	0.041	0.008	-10000	0	0	17	17
NOTCH/Deltex homolog 1	0.027	0.15	-10000	0	-0.44	44	44
PPP2R5D	0.017	0.066	-10000	0	-0.4	10	10
MAPK1	0.038	0.011	-10000	0	0	44	44
WNT1/LRP6/FZD1	0.076	0.059	-10000	0	-0.11	31	31
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.029	0.024	-10000	0	-0.017	85	85

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.012	0.16	-10000	0	-0.7	18	18
UGCG	-0.003	0.13	-10000	0	-0.67	18	18
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.021	0.18	0.27	2	-0.38	76	78
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.002	0.13	-10000	0	-0.66	18	18
mol:DAG	-0.008	0.028	0.17	12	-10000	0	12
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.036	0.22	0.28	1	-0.48	81	82
FRAP1	-0.055	0.26	0.29	3	-0.57	81	84
FOXO3	-0.052	0.25	0.26	2	-0.53	90	92
AKT1	-0.06	0.28	0.27	2	-0.58	90	92
GAB2	0.029	0.02	-10000	0	-0.003	149	149
SMPD1	0.002	0.12	-10000	0	-0.61	16	16
SGMS1	-0.003	0.038	0.059	12	-0.079	75	87
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	-0.019	0.034	-10000	0	-0.12	50	50
CALM1	0.039	0.009	-10000	0	0	26	26
cell proliferation	0.005	0.16	0.23	14	-0.31	73	87
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	0.02	0.062	-10000	0	-0.14	52	52
RPS6KB1	-0.022	0.2	-10000	0	-0.88	25	25
mol:sphingomyelin	-0.008	0.028	0.17	12	-10000	0	12
natural killer cell activation	-0.001	0.004	-10000	0	-0.014	24	24
JAK3	0.034	0.022	-10000	0	-0.046	24	24
PIK3R1	0.031	0.024	-10000	0	-0.041	26	26
JAK1	0.036	0.021	-10000	0	-0.043	24	24
NFKB1	0.036	0.013	-10000	0	0	66	66
MYC	-0.035	0.34	0.37	18	-0.8	76	94
MYB	-0.047	0.29	-10000	0	-1.1	39	39
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.024	0.17	0.27	2	-0.37	78	80
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.004	0.19	-10000	0	-0.81	25	25
mol:PI-3-4-5-P3	-0.024	0.17	0.27	2	-0.37	78	80
Rac1/GDP	0.008	0.044	-10000	0	-0.11	46	46
T cell proliferation	-0.027	0.16	0.28	6	-0.35	78	84
SHC1	0.037	0.016	-10000	0	-0.015	43	43
RAC1	0.039	0.009	-10000	0	0	28	28
positive regulation of cyclin-dependent protein kinase activity	0.001	0.019	0.031	39	-0.064	39	78
PRKCZ	-0.027	0.16	0.28	6	-0.36	77	83
NF kappa B1 p50/RelA	-0.026	0.24	0.3	2	-0.49	81	83
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.005	0.12	-10000	0	-0.34	39	39
HSP90AA1	0	0	-10000	0	-10000	0	0
RELA	0.04	0.006	-10000	0	0	10	10
IL2RA	0.036	0.017	-10000	0	-0.011	58	58
IL2RB	0.033	0.022	-10000	0	-0.046	20	20
TERT	0.037	0.012	-10000	0	0	53	53
E2F1	-0.006	0.12	-10000	0	-0.41	40	40
SOS1	0.035	0.018	-10000	0	-0.009	71	71
RPS6	0.039	0.01	-10000	0	0	32	32
mol:cAMP	-0.001	0.009	0.031	36	-0.016	39	75
PTPN11	0.035	0.02	-10000	0	-0.018	64	64
IL2RG	0.025	0.026	-10000	0	-0.041	28	28
actin cytoskeleton organization	-0.027	0.16	0.28	6	-0.35	78	84
GRB2	0.037	0.016	-10000	0	-0.015	41	41
IL2	0.035	0.024	-10000	0	-0.04	38	38
PIK3CA	0.027	0.024	-10000	0	-0.042	21	21
Rac1/GTP	0.029	0.061	-10000	0	-0.11	42	42
LCK	0.035	0.024	-10000	0	-0.039	41	41
BCL2	-0.029	0.2	0.38	1	-0.53	48	49

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.013	0.071	0.15	75	-0.18	5	80
DAPP1	-0.006	0.1	0.2	9	-0.24	51	60
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.015	0.14	-10000	0	-0.35	53	53
mol:DAG	0.002	0.075	0.17	21	-0.17	30	51
HRAS	0.04	0.013	0.076	3	-0.004	35	38
RAP1A	0.04	0.012	0.068	4	-0.001	36	40
ARF5/GDP	0.011	0.1	-10000	0	-0.24	42	42
PLCG2	0.035	0.015	-10000	0	0	82	82
PLCG1	0.038	0.011	-10000	0	0	43	43
ARF5	0.038	0.01	-10000	0	0	36	36
mol:GTP	-0.014	0.064	0.14	71	-0.18	4	75
ARF1/GTP	0.001	0.063	0.14	80	-0.16	4	84
RHOA	0.04	0.006	-10000	0	0	13	13
YES1	0.037	0.012	-10000	0	0	51	51
RAP1A/GTP	-0.006	0.074	0.16	77	-0.18	4	81
ADAP1	-0.015	0.059	0.13	68	-0.17	4	72
ARAP3	-0.014	0.064	0.14	71	-0.18	4	75
INPPL1	0.039	0.009	-10000	0	0	27	27
PREX1	0.038	0.012	-10000	0	0	48	48
ARHGEF6	0.036	0.013	-10000	0	0	64	64
ARHGEF7	0.039	0.009	-10000	0	0	28	28
ARF1	0.038	0.011	-10000	0	0	45	45
NRAS	0.041	0.011	0.069	3	0	30	33
FYN	0.034	0.016	-10000	0	0	94	94
ARF6	0.04	0.007	-10000	0	0	16	16
FGR	0.04	0.007	-10000	0	0	15	15
mol:Ca2+	-0.001	0.049	0.17	14	-0.11	9	23
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.036	0.013	-10000	0	0	66	66
ZAP70	0.041	0.005	-10000	0	0	9	9
mol:IP3	-0.004	0.062	0.21	14	-0.15	13	27
LYN	0.035	0.015	-10000	0	0	83	83
ARF1/GDP	0.014	0.097	-10000	0	-0.24	37	37
RhoA/GDP	0.032	0.084	0.19	46	-0.17	26	72
PDK1/Src/Hsp90	0.049	0.023	-10000	0	-0.11	6	6
BLNK	0.037	0.013	-10000	0	0	62	62
actin cytoskeleton reorganization	0.002	0.094	0.22	9	-0.26	24	33
SRC	0.039	0.009	-10000	0	0	28	28
PLEKHA2	-0.014	0.006	-10000	0	-10000	0	0
RAC1	0.039	0.009	-10000	0	0	28	28
PTEN	0.032	0.026	-10000	0	-0.03	71	71
HSP90AA1	0	0	-10000	0	-10000	0	0
ARF6/GTP	-0.013	0.073	0.15	77	-0.18	4	81
RhoA/GTP	-0.01	0.077	0.16	81	-0.18	5	86
Src family/SYK family/BLNK-LAT	-0.003	0.097	-10000	0	-0.27	37	37
BLK	0.033	0.017	-10000	0	0	114	114
PDPK1	0.039	0.009	-10000	0	0	29	29
CYTH1	-0.015	0.059	0.13	68	-0.17	4	72
HCK	0.036	0.013	-10000	0	0	65	65
CYTH3	-0.015	0.059	0.13	68	-0.17	4	72
CYTH2	-0.015	0.059	0.13	68	-0.17	4	72
KRAS	0.034	0.017	0.09	1	-0.001	98	99
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.008	0.047	0.2	1	-0.16	15	16
SGK1	0.008	0.046	-10000	0	-0.17	15	15
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.005	0.095	-10000	0	-0.25	41	41
SOS1	0.037	0.012	-10000	0	0	51	51
SYK	0.036	0.014	-10000	0	0	67	67
ARF6/GDP	-0.003	0.079	0.16	57	-0.18	18	75
mol:PI-3-4-5-P3	-0.015	0.063	0.14	68	-0.18	4	72
ARAP3/RAP1A/GTP	-0.006	0.074	0.16	77	-0.18	4	81
VAV1	0.036	0.014	-10000	0	0	69	69
mol:PI-3-4-P2	-0.01	0.002	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.042	0.063	0.22	23	-0.12	38	61
PLEKHA1	-0.015	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.014	0.1	-10000	0	-0.24	42	42
LAT	0.04	0.006	-10000	0	0	11	11
Rac1/GTP	-0.006	0.099	-10000	0	-0.26	50	50
ITK	-0.014	0.064	0.13	73	-0.18	5	78
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.003	0.093	0.2	16	-0.22	34	50
LCK	0.039	0.009	-10000	0	0	25	25
BTK	-0.016	0.067	0.14	70	-0.18	9	79

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.027	0.14	0.35	3	-0.5	23	26
CRKL	0.025	0.086	0.18	114	-0.15	1	115
mol:DAG	0.042	0.074	0.21	5	-0.23	17	22
HRAS	0.023	0.1	0.27	43	-0.18	3	46
MAPK8	0.014	0.083	0.19	83	-0.14	2	85
RAP1A	0.024	0.086	0.18	111	-0.17	3	114
GAB1	0.022	0.083	0.18	105	-0.15	1	106
MAPK14	0.016	0.086	0.19	88	-0.14	2	90
EPO	0.045	0.015	0.081	8	-0.037	7	15
PLCG1	0.042	0.075	0.21	5	-0.23	17	22
EPOR/TRPC2/IP3 Receptors	0.039	0.019	0.082	2	-0.037	6	8
RAPGEF1	0.039	0.009	-10000	0	0	26	26
EPO/EPOR (dimer)/SOCS3	0.063	0.051	-10000	0	-0.13	16	16
GAB1/SHC/GRB2/SOS1	0.067	0.081	0.24	28	-0.17	4	32
EPO/EPOR (dimer)	0.056	0.032	-10000	0	-0.14	2	2
IRS2	0.024	0.085	0.18	111	-0.15	1	112
STAT1	0.038	0.09	0.23	5	-0.24	31	36
STAT5B	0.046	0.079	0.22	6	-0.21	24	30
cell proliferation	0.007	0.081	0.18	83	-0.13	1	84
GAB1/SHIP/PIK3R1/SHP2/SHC	0.032	0.061	0.16	4	-0.16	6	10
TEC	0.019	0.081	0.18	97	-0.17	9	106
SOCS3	0.036	0.013	-10000	0	0	63	63
STAT1 (dimer)	0.038	0.089	0.23	5	-0.24	31	36
JAK2	0.037	0.02	0.081	6	-0.035	4	10
PIK3R1	0.034	0.016	-10000	0	0	99	99
EPO/EPOR (dimer)/JAK2	0.063	0.068	0.24	24	-0.1	30	54
EPO/EPOR	0.056	0.032	-10000	0	-0.14	2	2
LYN	0.035	0.018	-10000	0	-0.036	9	9
TEC/VAV2	0.032	0.076	0.22	22	-0.16	12	34
elevation of cytosolic calcium ion concentration	0.039	0.019	0.082	2	-0.036	6	8
SHC1	0.039	0.008	-10000	0	0	23	23
EPO/EPOR (dimer)/LYN	0.06	0.061	-10000	0	-0.12	28	28
mol:IP3	0.042	0.074	0.21	5	-0.23	17	22
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.045	0.074	0.18	82	-0.13	5	87
SH2B3	-0.001	0.007	0.031	10	-10000	0	10
NFKB1	0.013	0.082	0.19	75	-0.18	5	80
EPO/EPOR (dimer)/JAK2/SOCS3	0.011	0.052	-10000	0	-0.16	36	36
PTPN6	0.035	0.067	0.18	76	-0.1	28	104
TEC/VAV2/GRB2	0.049	0.084	0.23	27	-0.17	10	37
EPOR	0.039	0.019	0.082	2	-0.037	6	8
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.066	0.081	0.24	28	-0.17	4	32
SOS1	0.037	0.012	-10000	0	0	51	51
PLCG2	0.035	0.015	-10000	0	0	82	82
CRKL/CBL/C3G	0.071	0.076	0.24	37	-0.15	3	40
VAV2	0.021	0.083	0.18	103	-0.16	2	105
CBL	0.025	0.088	0.18	117	-0.22	1	118
SHC/Grb2/SOS1	0.036	0.056	0.17	2	-0.13	11	13
STAT5A	0.045	0.081	0.22	6	-0.22	25	31
GRB2	0.04	0.008	-10000	0	0	21	21
STAT5 (dimer)	0.062	0.093	0.28	4	-0.28	15	19
LYN/PLCgamma2	0.037	0.049	-10000	0	-0.13	32	32
PTPN11	0.039	0.009	-10000	0	0	29	29
BTK	0.023	0.087	0.18	110	-0.17	7	117
BCL2	0.03	0.12	0.34	3	-0.42	15	18

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.048	0.3	-10000	0	-1	47	47
CLOCK	0.031	0.031	-10000	0	-0.069	40	40
TIMELESS/CRY2	-0.049	0.31	-10000	0	-1	47	47
DEC1/BMAL1	0.044	0.047	-10000	0	-0.13	19	19
ATR	0.035	0.015	-10000	0	0	84	84
NR1D1	-0.013	0.11	-10000	0	-0.63	1	1
ARNTL	0.032	0.031	-10000	0	-0.068	42	42
TIMELESS	-0.08	0.32	-10000	0	-1.1	47	47
NPAS2	0.027	0.031	-10000	0	-0.067	36	36
CRY2	0.041	0.004	-10000	0	0	5	5
mol:CO	0.001	0.04	0.13	47	-10000	0	47
CHEK1	0.032	0.017	-10000	0	0	118	118
mol:HEME	-0.001	0.04	-10000	0	-0.13	47	47
PER1	0.038	0.011	-10000	0	0	44	44
BMAL/CLOCK/NPAS2	0.029	0.095	-10000	0	-0.13	112	112
BMAL1/CLOCK	-0.037	0.2	-10000	0	-0.58	49	49
S phase of mitotic cell cycle	-0.048	0.3	-10000	0	-1	47	47
TIMELESS/CHEK1/ATR	-0.05	0.31	-10000	0	-1	47	47
mol:NADPH	-0.001	0.04	-10000	0	-0.13	47	47
PER1/TIMELESS	-0.052	0.31	-10000	0	-1	47	47
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.04	0.008	-10000	0	0	19	19

×

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

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
BAG4	0.037	0.012	-10000	0	0	55	55
Caspase 8 (4 units)	0.037	0.092	-10000	0	-0.24	27	27
NEF	0.003	0.005	-10000	0	-0.1	1	1
NFKBIA	0.025	0.043	0.084	9	-0.068	79	88
BIRC3	-0.059	0.1	0.18	5	-0.28	89	94
CYCS	-0.004	0.062	0.18	7	-0.26	13	20
RIPK1	0.039	0.01	-10000	0	0	32	32
CD247	0.003	0.005	-10000	0	-0.1	1	1
MAP2K7	-0.006	0.17	-10000	0	-0.56	34	34
protein ubiquitination	-0.002	0.098	0.2	5	-0.26	38	43
CRADD	0.04	0.006	-10000	0	0	10	10
DAXX	0.04	0.006	-10000	0	0	11	11
FAS	0.035	0.015	-10000	0	0	88	88
BID	0.005	0.06	0.18	3	-0.26	12	15
NF-kappa-B/RelA/I kappa B alpha	0.027	0.11	-10000	0	-0.17	117	117
TRADD	0.037	0.013	-10000	0	0	61	61
MAP3K5	0.037	0.013	-10000	0	0	60	60
CFLAR	0.04	0.008	-10000	0	0	19	19
FADD	0.04	0.008	-10000	0	0	20	20
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.027	0.11	-10000	0	-0.18	117	117
MAPK8	-0.01	0.16	-10000	0	-0.54	32	32
APAF1	0.039	0.009	-10000	0	0	28	28
TRAF1	0.04	0.007	-10000	0	0	17	17
TRAF2	0.039	0.01	-10000	0	0	32	32
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.013	0.067	-10000	0	-0.27	14	14
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.006	0.12	0.21	1	-0.32	37	38
CHUK	-0.003	0.1	0.21	4	-0.28	39	43
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.077	0.083	-10000	0	-0.12	56	56
TCRz/NEF	0.01	0.008	-10000	0	-0.17	1	1
TNF	0.04	0.008	-10000	0	0	22	22
FASLG	0.022	0.014	-10000	0	-0.29	1	1
NFKB1	0.027	0.041	0.095	2	-0.07	68	70
TNFR1A/BAG4/TNF-alpha	0.06	0.045	-10000	0	-0.11	15	15
CASP6	-0.039	0.23	-10000	0	-0.53	84	84
CASP7	-0.042	0.2	0.27	9	-0.41	103	112
RELA	0.027	0.045	0.082	9	-0.066	96	105
CASP2	0.038	0.011	-10000	0	0	41	41
CASP3	-0.054	0.2	0.28	8	-0.41	111	119
TNFRSF1A	0.036	0.014	-10000	0	0	72	72
TNFR1A/BAG4	0.045	0.037	-10000	0	-0.13	14	14
CASP8	0.039	0.009	-10000	0	0	27	27
CASP9	0.039	0.008	-10000	0	0	24	24
MAP3K14	0.003	0.11	0.2	5	-0.3	36	41
APAF-1/Caspase 9	-0.025	0.11	0.19	1	-0.24	92	93
BCL2	-0.009	0.14	-10000	0	-0.49	32	32

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.005	0.067	-10000	0	-0.19	48	48
epithelial cell differentiation	0.058	0.066	-10000	0	-0.12	48	48
CYFIP2	0.038	0.011	-10000	0	0	45	45
ENAH	-0.036	0.067	0.19	11	-0.2	7	18
EGFR	0.036	0.014	-10000	0	0	67	67
EPHA2	0.039	0.009	-10000	0	0	26	26
MYO6	-0.029	0.048	0.18	9	-0.2	16	25
CTNNB1	0.039	0.01	-10000	0	0	32	32
ABI1/Sra1/Nap1	0.061	0.057	-10000	0	-0.12	39	39
AQP5	-0.069	0.14	-10000	0	-0.37	88	88
CTNND1	0.04	0.007	-10000	0	0	17	17
mol:PI-4-5-P2	-0.029	0.044	0.18	9	-0.19	12	21
regulation of calcium-dependent cell-cell adhesion	-0.029	0.041	0.17	6	-0.19	12	18
EGF	0.038	0.01	-10000	0	0	38	38
NCKAP1	0.039	0.009	-10000	0	0	26	26
AQP3	-0.018	0.048	-10000	0	-0.28	8	8
cortical microtubule organization	0.058	0.066	-10000	0	-0.12	48	48
GO:0000145	-0.028	0.04	0.16	9	-0.18	12	21
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.065	0.069	-10000	0	-0.12	48	48
MLLT4	0.033	0.016	-10000	0	0	109	109
ARF6/GDP	-0.052	0.047	-10000	0	-0.19	28	28
ARF6	0.04	0.007	-10000	0	0	16	16
Ephrin A1/EPHA2/NCK1/GIT1	0.06	0.078	-10000	0	-0.12	66	66
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.015	0.046	0.17	6	-0.19	15	21
PVRL2	0.037	0.012	-10000	0	0	51	51
ZYX	-0.026	0.042	0.18	9	-0.19	8	17
ARF6/GTP	0.065	0.084	-10000	0	-0.12	68	68
CDH1	0.035	0.014	-10000	0	0	79	79
EGFR/EGFR/EGF/EGF	0.039	0.073	-10000	0	-0.12	72	72
RhoA/GDP	0.058	0.068	-10000	0	-0.12	52	52
actin cytoskeleton organization	-0.031	0.048	0.16	9	-0.21	17	26
IGF-1R heterotetramer	0.033	0.017	-10000	0	0	112	112
GIT1	0.039	0.009	-10000	0	0	25	25
IGF1R	0.033	0.017	-10000	0	0	112	112
IGF1	0.035	0.014	-10000	0	0	77	77
DIAPH1	-0.003	0.22	-10000	0	-0.56	71	71
Wnt receptor signaling pathway	-0.058	0.066	0.12	48	-10000	0	48
RHOA	0.04	0.006	-10000	0	0	13	13
RhoA/GTP	-0.051	0.046	-10000	0	-0.18	28	28
CTNNA1	0.039	0.01	-10000	0	0	31	31
VCL	-0.031	0.049	0.16	9	-0.22	17	26
EFNA1	0.034	0.016	-10000	0	0	96	96
LPP	-0.029	0.044	0.16	8	-0.19	13	21
Ephrin A1/EPHA2	0.035	0.075	-10000	0	-0.12	77	77
SEC6/SEC8	-0.04	0.041	-10000	0	-0.18	18	18
MGAT3	-0.029	0.042	0.18	6	-0.19	12	18
HGF/MET	0.019	0.084	-10000	0	-0.12	110	110
HGF	0.039	0.009	-10000	0	0	27	27
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.005	0.068	-10000	0	-0.19	48	48
actin cable formation	0	0.094	0.25	22	-0.23	23	45
KIAA1543	-0.033	0.042	0.16	8	-0.2	12	20
KIFC3	-0.031	0.044	0.18	9	-0.19	12	21
NCK1	0.036	0.014	-10000	0	0	70	70
EXOC3	0.037	0.012	-10000	0	0	55	55
ACTN1	-0.03	0.048	0.18	10	-0.2	15	25
NCK1/GIT1	0.043	0.047	-10000	0	-0.13	31	31
mol:GDP	0.058	0.066	-10000	0	-0.12	48	48
EXOC4	0.038	0.011	-10000	0	0	41	41
STX4	-0.029	0.032	0.038	7	-0.12	46	53
PIP5K1C	-0.029	0.044	0.18	9	-0.19	12	21
LIMA1	0	0	-10000	0	-10000	0	0
ABI1	0.039	0.009	-10000	0	0	28	28
ROCK1	-0.03	0.08	0.22	12	-0.23	6	18
adherens junction assembly	-0.043	0.12	-10000	0	-0.38	36	36
IGF-1R heterotetramer/IGF1	0.025	0.08	-10000	0	-0.12	95	95
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.038	0.047	-10000	0	-0.14	27	27
MET	0.027	0.02	-10000	0	0	191	191
PLEKHA7	-0.03	0.046	0.18	10	-0.2	13	23
mol:GTP	0.057	0.076	-10000	0	-0.12	66	66
establishment of epithelial cell apical/basal polarity	-0.02	0.074	0.15	66	-0.2	13	79
cortical actin cytoskeleton stabilization	0.005	0.067	-10000	0	-0.19	48	48
regulation of cell-cell adhesion	-0.031	0.048	0.16	9	-0.21	17	26
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.005	0.068	-10000	0	-0.19	48	48

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.009	0.038	-10000	0	-0.11	62	62
STMN1	-0.012	0.014	0.024	15	-10000	0	15
Aurora B/RasGAP/Survivin	0.047	0.072	-10000	0	-0.15	49	49
Chromosomal passenger complex/Cul3 protein complex	-0.006	0.089	-10000	0	-0.24	44	44
BIRC5	0.037	0.014	-10000	0	-0.003	56	56
DES	-0.051	0.28	-10000	0	-0.8	63	63
Aurora C/Aurora B/INCENP	0.059	0.047	-10000	0	-0.11	26	26
Aurora B/TACC1	0.037	0.038	-10000	0	-0.11	22	22
Aurora B/PP2A	0.044	0.048	-10000	0	-0.14	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	-0.011	0.061	-10000	0	-0.16	72	72
mitotic metaphase/anaphase transition	0.002	0.006	0.013	109	-10000	0	109
NDC80	-0.005	0.009	0.019	11	-10000	0	11
Cul3 protein complex	0.049	0.06	-10000	0	-0.12	45	45
KIF2C	-0.058	0.19	-10000	0	-0.49	78	78
PEBP1	-0.001	0.003	-10000	0	-0.011	38	38
KIF20A	0.032	0.018	-10000	0	0	125	125
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.037	0.055	-10000	0	-0.14	43	43
SEPT1	0.04	0.007	-10000	0	0	17	17
SMC2	0	0	-10000	0	-10000	0	0
SMC4	0	0	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.045	0.2	0.27	1	-0.56	63	64
PSMA3	0.037	0.012	-10000	0	0	51	51
G2/M transition of mitotic cell cycle	-0.001	0.003	0.009	36	-0.008	17	53
H3F3B	0.002	0.056	-10000	0	-0.2	38	38
AURKB	0.037	0.016	0.066	1	0	79	80
AURKC	0.039	0.01	-10000	0	0	34	34
CDCA8	0.036	0.015	-10000	0	-0.005	58	58
cytokinesis	-0.032	0.18	-10000	0	-0.46	64	64
Aurora B/Septin1	-0.009	0.19	-10000	0	-0.45	61	61
AURKA	-0.001	0.003	0.009	36	-0.008	17	53
INCENP	0.038	0.015	-10000	0	-0.029	26	26
KLHL13	0.032	0.017	-10000	0	0	117	117
BUB1	0.037	0.015	-10000	0	0	72	72
hSgo1/Aurora B/Survivin	0.041	0.077	-10000	0	-0.15	59	59
EVI5	0.039	0.01	-10000	0	0	33	33
RhoA/GTP	0	0.16	-10000	0	-0.36	66	66
SGOL1	0.036	0.014	-10000	0	0	69	69
CENPA	-0.017	0.11	-10000	0	-0.29	61	61
NCAPG	0	0	-10000	0	-10000	0	0
Aurora B/HC8 Proteasome	0.034	0.063	-10000	0	-0.14	56	56
NCAPD2	0	0	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.036	0.061	-10000	0	-0.14	53	53
RHOA	0.04	0.006	-10000	0	0	13	13
NCAPH	0	0	-10000	0	-10000	0	0
NPM1	-0.027	0.15	-10000	0	-0.36	70	70
RASA1	0.037	0.013	-10000	0	0	56	56
KLHL9	0.039	0.01	-10000	0	0	34	34
mitotic prometaphase	-0.001	0.003	-10000	0	-0.011	38	38
proteasomal ubiquitin-dependent protein catabolic process	0.033	0.063	-10000	0	-0.14	56	56
PPP1CC	0.039	0.01	-10000	0	0	32	32
Centraspindlin	-0.012	0.17	-10000	0	-0.38	70	70
RhoA/GDP	0.029	0.014	-10000	0	-0.12	4	4
NSUN2	-0.015	0.12	-10000	0	-0.32	68	68
MYLK	0.001	0.056	-10000	0	-0.2	39	39
KIF23	0.035	0.016	-10000	0	0	93	93
VIM	-0.012	0.014	0.023	15	-10000	0	15
RACGAP1	0.037	0.014	-10000	0	-0.004	52	52
mitosis	0	0	-10000	0	-10000	0	0
NCL	-0.03	0.13	-10000	0	-0.32	86	86
Chromosomal passenger complex	-0.035	0.14	-10000	0	-0.35	67	67
Chromosomal passenger complex/EVI5	0.067	0.095	-10000	0	-0.17	55	55
TACC1	0.035	0.015	-10000	0	0	86	86
PPP2R5D	0.039	0.009	-10000	0	0	26	26
CUL3	0.04	0.008	-10000	0	0	19	19
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.023	0.012	-10000	0	-0.1	1	1
ARNO/beta Arrestin1-2	0.041	0.033	-10000	0	-0.087	10	10
EGFR	0.036	0.014	-10000	0	0	67	67
EPHA2	0.039	0.009	-10000	0	0	26	26
USP6	0.038	0.011	-10000	0	0	42	42
IQSEC1	0.04	0.006	-10000	0	0	13	13
EGFR/EGFR/EGF/EGF	0.041	0.05	-10000	0	-0.13	35	35
ARRB2	0.016	0.017	-10000	0	-0.2	3	3
mol:GTP	0.002	0.017	0.12	5	-0.06	14	19
ARRB1	0.038	0.012	-10000	0	0	48	48
FBXO8	0.037	0.013	-10000	0	0	59	59
TSHR	0.037	0.012	-10000	0	0	54	54
EGF	0.038	0.01	-10000	0	0	38	38
somatostatin receptor activity	0	0	0	9	-0.001	38	47
ARAP2	0	0	0	11	0	35	46
mol:GDP	0.011	0.072	0.15	3	-0.19	31	34
mol:PI-3-4-5-P3	0	0	0	7	0	37	44
ITGA2B	0.04	0.008	-10000	0	0	22	22
ARF6	0.04	0.007	-10000	0	0	16	16
Ephrin A1/EPHA2/NCK1/GIT1	0.06	0.078	-10000	0	-0.12	66	66
ADAP1	0	0	0	9	0	23	32
KIF13B	0.034	0.016	-10000	0	0	95	95
HGF/MET	0.013	0.074	-10000	0	-0.13	102	102
PXN	0.04	0.006	-10000	0	0	10	10
ARF6/GTP	0.013	0.081	0.19	4	-0.21	38	42
EGFR/EGFR/EGF/EGF/ARFGEP100	0.06	0.053	-10000	0	-0.12	33	33
ADRB2	0.04	0.006	-10000	0	0	11	11
receptor agonist activity	0	0	0	8	0	35	43
actin filament binding	0	0	0	6	0	39	45
SRC	0.039	0.009	-10000	0	0	28	28
ITGB3	0.032	0.017	-10000	0	0	116	116
GNAQ	0.038	0.012	-10000	0	0	48	48
EFA6/PI-4-5-P2	0	0	0.001	13	-0.001	26	39
ARF6/GDP	0.008	0.075	0.18	8	-0.22	29	37
ARF6/GDP/GULP/ACAP1	0.025	0.085	-10000	0	-0.22	24	24
alphaIIb/beta3 Integrin/paxillin/GIT1	0.079	0.057	-10000	0	-0.11	35	35
ACAP1	0	0	0	6	-10000	0	6
ACAP2	0	0	0	8	0	36	44
LHCGR/beta Arrestin2	0.03	0.027	-10000	0	-0.062	37	37
EFNA1	0.034	0.016	-10000	0	0	96	96
HGF	0.039	0.009	-10000	0	0	27	27
CYTH3	0	0	0.001	10	-0.001	35	45
CYTH2	0	0.001	0.003	6	-0.004	36	42
NCK1	0.036	0.014	-10000	0	0	70	70
fibronectin binding	0	0	0	8	0	29	37
endosomal lumen acidification	0	0	0	12	0	17	29
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	0.032	0.017	-10000	0	0	127	127
GNAQ/ARNO	0.026	0.008	-10000	0	0	48	48
mol:Phosphatidic acid	0	0	0	8	0	36	44
PIP3-E	0.038	0.011	-10000	0	0	45	45
MET	0.027	0.02	-10000	0	0	191	191
GNA14	0.039	0.009	-10000	0	0	29	29
GNA15	0.036	0.014	-10000	0	0	68	68
GIT1	0.039	0.009	-10000	0	0	25	25
mol:PI-4-5-P2	0	0	0.001	13	-0.001	37	50
GNA11	0.037	0.013	-10000	0	0	61	61
LHCGR	0.04	0.008	-10000	0	0	20	20
AGTR1	0.037	0.013	-10000	0	0	57	57
desensitization of G-protein coupled receptor protein signaling pathway	0.03	0.027	-10000	0	-0.062	37	37
IPCEF1/ARNO	0.051	0.046	-10000	0	-0.086	34	34
alphaIIb/beta3 Integrin	0.039	0.05	-10000	0	-0.13	35	35

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	0.037	0.012	-10000	0	0	52	52
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.039	0.008	-10000	0	0	23	23
TCEB1	0.038	0.011	-10000	0	0	39	39
HIF1A/p53	0.004	0.078	0.22	1	-0.25	33	34
HIF1A	0	0.068	0.16	2	-0.25	24	26
COPS5	0.035	0.014	-10000	0	0	79	79
VHL/Elongin B/Elongin C/RBX1/CUL2	0.083	0.071	-10000	0	-0.12	31	31
FIH (dimer)	0.04	0.008	-10000	0	0	20	20
CDKN2A	0.029	0.019	-10000	0	0	167	167
ARNT/IPAS	0.05	0.028	-10000	0	-0.13	4	4
HIF1AN	0.04	0.008	-10000	0	0	20	20
GNB2L1	0.039	0.009	-10000	0	0	30	30
HIF1A/ARNT	0.015	0.076	0.22	1	-0.25	26	27
CUL2	0.039	0.01	-10000	0	0	34	34
OS9	0.039	0.009	-10000	0	0	26	26
RACK1/Elongin B/Elongin C	0.068	0.039	-10000	0	-0.12	11	11
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	-0.003	0.067	0.15	2	-0.3	16	18
PHD1-3/OS9	0.05	0.079	-10000	0	-0.11	88	88
HIF1A/RACK1/Elongin B/Elongin C	0.049	0.084	-10000	0	-0.25	22	22
VHL	0.039	0.008	-10000	0	0	23	23
HSP90AA1	0	0	-10000	0	-10000	0	0
HIF1A/JAB1	0.015	0.074	0.22	1	-0.25	24	25
EGLN3	0.027	0.019	-10000	0	0	182	182
EGLN2	0.038	0.011	-10000	0	0	41	41
EGLN1	0.039	0.009	-10000	0	0	29	29
TP53	0.026	0.02	-10000	0	0	207	207
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.029	0.11	-10000	0	-0.55	18	18
ARNT	0.037	0.012	-10000	0	0	50	50
ARD1A	0.039	0.009	-10000	0	0	30	30
RBX1	0.036	0.014	-10000	0	0	70	70
HIF1A/p19ARF	0.006	0.08	-10000	0	-0.26	29	29

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	0.046	0.05	-10000	0	-0.14	35	35
Necdin/E2F1	0.043	0.039	-10000	0	-0.14	14	14
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.071	0.059	-10000	0	-0.11	40	40
NGF (dimer)/p75(NTR)/BEX1	0.022	0.052	-10000	0	-0.11	61	61
NT-4/5 (dimer)/p75(NTR)	0.029	0.009	-10000	0	-0.12	1	1
IKBKB	0.038	0.011	-10000	0	0	41	41
AKT1	0.026	0.097	0.19	124	-0.18	6	130
IKBKG	0.041	0.002	-10000	0	0	2	2
BDNF	0.04	0.006	-10000	0	0	12	12
MGDIs/NGR/p75(NTR)/LINGO1	0.048	0.021	-10000	0	-0.11	3	3
FURIN	0.039	0.01	-10000	0	0	31	31
proBDNF (dimer)/p75(NTR)/Sortilin	0.068	0.046	-10000	0	-0.12	25	25
LINGO1	0	0	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	0.016	0.068	-10000	0	-0.13	72	72
proBDNF (dimer)	0.04	0.006	-10000	0	0	12	12
NTRK1	0.04	0.007	-10000	0	0	16	16
RTN4R	0.037	0.012	-10000	0	0	50	50
neuron apoptosis	-0.069	0.15	-10000	0	-0.38	68	68
IRAK1	0.04	0.008	-10000	0	0	19	19
SHC1	0.017	0.009	0.069	7	-0.11	1	8
ARHGDIA	0.037	0.012	-10000	0	0	53	53
RhoA/GTP	0.029	0.014	-10000	0	-0.12	4	4
Gamma Secretase	0.067	0.085	-10000	0	-0.12	63	63
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.055	0.056	-10000	0	-0.1	49	49
MAGEH1	0.038	0.011	-10000	0	0	44	44
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.051	0.052	-10000	0	-0.1	37	37
Mammalian IAPs/DIABLO	0.012	0.088	-10000	0	-0.13	129	129
proNGF (dimer)	0	0	-10000	0	-10000	0	0
MAGED1	0.039	0.008	-10000	0	0	24	24
APP	0.038	0.011	-10000	0	0	41	41
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
ZNF274	0.038	0.01	-10000	0	0	38	38
RhoA/GDP/RHOGDI	0.048	0.027	0.19	3	-0.11	7	10
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	-0.014	0.045	0.2	8	-10000	0	8
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.01	0.062	-10000	0	-0.16	50	50
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.05	0.024	-10000	0	-0.11	8	8
NCSTN	0.04	0.008	-10000	0	0	22	22
mol:GTP	0.044	0.034	-10000	0	-0.1	23	23
PSENEN	0.034	0.016	-10000	0	0	96	96
mol:ceramide	-0.018	0.036	0.2	10	-10000	0	10
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.009	0.09	-10000	0	-0.32	21	21
p75(NTR)/beta APP	0.048	0.043	-10000	0	-0.13	26	26
BEX1	0.026	0.02	-10000	0	0	200	200
mol:GDP	-0.008	0.004	-10000	0	-0.1	1	1
NGF (dimer)	-0.004	0.074	-10000	0	-0.1	172	172
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.063	0.035	-10000	0	-0.1	7	7
PIK3R1	0.034	0.016	-10000	0	0	99	99
RAC1/GTP	0.044	0.015	-10000	0	-0.09	1	1
MYD88	0.04	0.006	-10000	0	0	12	12
CHUK	0.038	0.011	-10000	0	0	46	46
NGF (dimer)/p75(NTR)/PKA	0.045	0.035	-10000	0	-0.11	23	23
RHOB	0.04	0.007	-10000	0	0	16	16
RHOA	0.04	0.006	-10000	0	0	13	13
MAGE-G1/E2F1	0.052	0.024	-10000	0	-0.13	2	2
NT3 (dimer)	0.031	0.018	-10000	0	0	133	133
TP53	-0.022	0.047	0.17	14	-0.18	13	27
PRDM4	-0.02	0.036	0.2	9	-10000	0	9
BDNF (dimer)	0.016	0.09	-10000	0	-0.11	168	168
PIK3CA	0.029	0.019	-10000	0	0	166	166
SORT1	0.038	0.011	-10000	0	0	42	42
activation of caspase activity	0.064	0.056	-10000	0	-0.1	40	40
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.062	0.048	-10000	0	-0.11	33	33
RHOC	0.04	0.006	-10000	0	0	10	10
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	-0.012	0.057	0.22	7	-0.2	10	17
DIABLO	0.037	0.013	-10000	0	0	61	61
SMPD2	-0.019	0.036	0.2	10	-10000	0	10
APH1B	0.035	0.014	-10000	0	0	79	79
APH1A	0.038	0.011	-10000	0	0	42	42
proNGF (dimer)/p75(NTR)/Sortilin	0.044	0.037	-10000	0	-0.11	26	26
PSEN1	0.039	0.01	-10000	0	0	31	31
APAF-1/Pro-Caspase 9	0.051	0.039	-10000	0	-0.14	18	18
NT3 (dimer)/p75(NTR)	0.042	0.034	-10000	0	-0.13	8	8
MAPK8	-0.017	0.064	0.24	5	-0.23	13	18
MAPK9	-0.017	0.061	0.24	5	-0.21	12	17
APAF1	0.039	0.009	-10000	0	0	28	28
NTF3	0.031	0.018	-10000	0	0	133	133
NTF4	0	0	-10000	0	-10000	0	0
NDN	0.034	0.016	-10000	0	0	99	99
RAC1/GDP	0.029	0.009	-10000	0	-0.12	1	1
RhoA-B-C/GDP	0.073	0.049	-10000	0	-0.1	27	27
p75 CTF/Sortilin/TRAF6/NRIF	0.069	0.075	-10000	0	-0.13	56	56
RhoA-B-C/GTP	0.044	0.034	-10000	0	-0.1	23	23
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.093	0.066	-10000	0	-0.11	32	32
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.085	0.057	-10000	0	-0.11	32	32
PRKACB	0.038	0.011	-10000	0	0	44	44
proBDNF (dimer)/p75 ECD	0.047	0.046	-10000	0	-0.13	31	31
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.025	0.02	-10000	0	0	210	210
BIRC2	0.036	0.014	-10000	0	0	72	72
neuron projection morphogenesis	-0.018	0.049	0.12	7	-0.16	22	29
BAD	-0.019	0.068	0.23	5	-0.21	18	23
RIPK2	0.032	0.017	-10000	0	0	119	119
NGFR	0.039	0.009	-10000	0	0	25	25
CYCS	-0.024	0.04	0.2	8	-0.18	5	13
ADAM17	0.037	0.012	-10000	0	0	52	52
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.049	0.056	-10000	0	-0.11	44	44
BCL2L11	-0.02	0.068	0.23	5	-0.21	18	23
BDNF (dimer)/p75(NTR)	0.057	0.017	-10000	0	-0.13	1	1
PI3K	0.034	0.058	-10000	0	-0.11	45	45
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.061	0.046	-10000	0	-0.1	27	27
NDNL2	0.038	0.011	-10000	0	0	40	40
YWHAE	0.037	0.013	-10000	0	0	58	58
PRKCI	0.027	0.02	-10000	0	0	192	192
NGF (dimer)/p75(NTR)	0.029	0.009	-10000	0	-0.12	1	1
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.06	0.051	-10000	0	-0.1	38	38
TRAF6	0.04	0.008	-10000	0	0	19	19
RAC1	0.039	0.009	-10000	0	0	28	28
PRKCZ	0.039	0.009	-10000	0	0	27	27
PLG	0.038	0.011	-10000	0	0	41	41
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	0.014	0.044	0.16	8	-0.17	23	31
SQSTM1	0.038	0.011	-10000	0	0	46	46
NGFRAP1	0.04	0.007	-10000	0	0	15	15
CASP3	-0.021	0.071	0.24	4	-0.22	25	29
E2F1	0.038	0.011	-10000	0	0	39	39
CASP9	0.039	0.008	-10000	0	0	24	24
IKK complex	0.045	0.1	-10000	0	-0.25	27	27
NGF (dimer)/TRKA	0.03	0.005	-10000	0	-10000	0	0
MMP7	0.016	0.02	-10000	0	0	333	333
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.074	0.055	-10000	0	-0.1	33	33
MMP3	0.037	0.012	-10000	0	0	53	53
APAF-1/Caspase 9	-0.056	0.059	-10000	0	-0.19	51	51

×

S1P3 pathway

Figure S68. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S68. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.036	0.013	-10000	0	0	65	65
mol:S1P	0.001	0.007	-10000	0	-0.028	23	23
S1P1/S1P/Gi	0.007	0.079	-10000	0	-0.18	62	62
GNAO1	0.034	0.023	-10000	0	-0.009	105	105
S1P/S1P3/G12/G13	0.047	0.03	-10000	0	-0.064	23	23
AKT1	0.015	0.099	-10000	0	-0.45	19	19
AKT3	-0.019	0.23	-10000	0	-0.91	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.036	0.013	-10000	0	0	65	65
GNAI2	0.039	0.019	-10000	0	-0.03	35	35
GNAI3	0.037	0.019	-10000	0	-0.013	62	62
GNAI1	0.034	0.022	-10000	0	-0.007	110	110
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.001	0.007	0.011	3	-0.029	23	26
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	0.04	0.006	-10000	0	0	11	11
mol:Ca2+	0	0.1	0.16	3	-0.27	46	49
MAPK3	-0.009	0.094	0.14	4	-0.25	51	55
MAPK1	-0.005	0.09	0.14	4	-0.26	41	45
JAK2	-0.015	0.11	0.2	3	-0.29	54	57
CXCR4	-0.01	0.099	0.14	7	-0.27	49	56
FLT1	0.04	0.022	-10000	0	-0.024	48	48
RhoA/GDP	0.029	0.014	-10000	0	-0.12	4	4
Rac1/GDP	0.029	0.009	-10000	0	-0.12	1	1
SRC	-0.009	0.093	0.14	3	-0.26	46	49
S1P/S1P3/Gi	0	0.1	0.16	3	-0.28	45	48
RAC1	0.039	0.009	-10000	0	0	28	28
RhoA/GTP	0.012	0.1	-10000	0	-0.24	51	51
VEGFA	0.003	0.01	0.017	98	-0.038	22	120
S1P/S1P2/Gi	-0.003	0.088	0.14	3	-0.19	77	80
VEGFR1 homodimer/VEGFA homodimer	0.036	0.032	-10000	0	-0.087	25	25
RHOA	0.04	0.006	-10000	0	0	13	13
S1P/S1P3/Gq	0.017	0.04	-10000	0	-0.15	26	26
GNAQ	0.038	0.012	-10000	0	0	48	48
GNAZ	0.037	0.02	-10000	0	-0.013	64	64
G12/G13	0.053	0.028	-10000	0	-0.13	8	8
GNA14	0.039	0.009	-10000	0	0	29	29
GNA15	0.036	0.014	-10000	0	0	68	68
GNA12	0.039	0.01	-10000	0	0	33	33
GNA13	0.039	0.008	-10000	0	0	23	23
GNA11	0.037	0.013	-10000	0	0	61	61
Rac1/GTP	0.01	0.1	-10000	0	-0.25	49	49

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.008	0.053	0.18	46	-0.088	3	49
BUB1B	-0.024	0.081	-10000	0	-0.21	67	67
PLK1	-0.003	0.036	0.08	2	-0.099	42	44
PLK1S1	-0.002	0.02	0.046	3	-0.054	41	44
KIF2A	-0.003	0.032	0.071	2	-0.089	42	44
regulation of mitotic centrosome separation	-0.003	0.036	0.08	2	-0.099	42	44
GOLGA2	0.04	0.008	-10000	0	0	22	22
Hec1/SPC24	-0.01	0.025	-10000	0	-0.08	47	47
WEE1	-0.01	0.083	-10000	0	-0.34	22	22
cytokinesis	-0.037	0.13	0.15	2	-0.3	89	91
PP2A-alpha B56	0	0.24	-10000	0	-0.7	57	57
AURKA	-0.002	0.022	0.051	4	-0.063	34	38
PICH/PLK1	-0.034	0.068	-10000	0	-0.16	106	106
CENPE	-0.008	0.035	0.15	2	-0.13	20	22
RhoA/GTP	0.029	0.014	-10000	0	-0.12	4	4
positive regulation of microtubule depolymerization	-0.003	0.032	0.071	2	-0.089	42	44
PPP2CA	0.04	0.008	-10000	0	0	22	22
FZR1	0.037	0.012	-10000	0	0	54	54
TPX2	-0.026	0.096	-10000	0	-0.25	84	84
PAK1	0.037	0.014	-10000	0	0	65	65
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	0.04	0.008	-10000	0	0	22	22
CLSPN	0.008	0.034	-10000	0	-0.28	5	5
GORASP1	0.041	0.005	-10000	0	0	8	8
metaphase	0	0.004	0.015	9	-0.013	27	36
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.002	0.02	0.046	3	-0.054	41	44
G2 phase of mitotic cell cycle	-0.001	0.003	0.012	9	-10000	0	9
STAG2	0.039	0.01	-10000	0	0	34	34
GRASP65/GM130/RAB1/GTP	0.017	0.065	-10000	0	-0.64	4	4
spindle elongation	-0.003	0.036	0.08	2	-0.099	42	44
ODF2	0.04	0.009	-10000	0	0	24	24
BUB1	-0.041	0.24	-10000	0	-0.74	57	57
TPT1	-0.002	0.049	-10000	0	-0.19	29	29
CDC25C	-0.007	0.088	-10000	0	-0.34	33	33
CDC25B	0.024	0.03	-10000	0	-0.03	114	114
SGOL1	-0.008	0.053	0.088	3	-0.18	46	49
RHOA	0.04	0.006	-10000	0	0	13	13
CCNB1/CDK1	0.005	0.12	-10000	0	-0.21	117	117
CDC14B	-0.01	0.006	0.011	31	-10000	0	31
CDC20	0.034	0.016	-10000	0	0	96	96
PLK1/PBIP1	-0.004	0.032	-10000	0	-0.1	34	34
mitosis	-0.001	0.003	0.012	6	-0.012	4	10
FBXO5	-0.016	0.063	0.11	2	-0.18	54	56
CDC2	0.027	0.023	-10000	0	-0.028	30	30
NDC80	0	0	-10000	0	-10000	0	0
metaphase plate congression	0.002	0.052	-10000	0	-0.25	19	19
ERCC6L	-0.029	0.098	-10000	0	-0.2	113	113
NLP/gamma Tubulin	-0.003	0.031	0.062	2	-0.088	46	48
microtubule cytoskeleton organization	-0.002	0.049	-10000	0	-0.19	29	29
G2/M transition DNA damage checkpoint	0	0.002	0.011	9	-10000	0	9
PPP1R12A	0.04	0.009	-10000	0	0	24	24
interphase	0	0.002	0.011	9	-10000	0	9
PLK1/PRC1-2	0.013	0.083	-10000	0	-0.15	87	87
GRASP65/GM130/RAB1/GTP/PLK1	0.051	0.058	-10000	0	-0.1	42	42
RAB1A	0.039	0.009	-10000	0	0	26	26
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.002	0.025	0.063	5	-0.068	38	43
mitotic prometaphase	-0.001	0.004	0.018	19	-10000	0	19
proteasomal ubiquitin-dependent protein catabolic process	-0.005	0.078	-10000	0	-0.27	27	27
microtubule-based process	0.014	0.051	0.096	1	-0.14	35	36
Golgi organization	-0.003	0.036	0.08	2	-0.099	42	44
Cohesin/SA2	0.013	0.046	0.091	1	-0.096	59	60
PPP1CB/MYPT1	0.051	0.04	-10000	0	-0.14	22	22
KIF20A	0.032	0.017	-10000	0	0	125	125
APC/C/CDC20	0.016	0.05	-10000	0	-0.14	36	36
PPP2R1A	0.039	0.009	-10000	0	0	28	28
chromosome segregation	-0.004	0.031	-10000	0	-0.099	34	34
PRC1	0.035	0.015	-10000	0	0	80	80
ECT2	0.034	0.11	0.22	129	-0.15	48	177
C13orf34	-0.002	0.029	0.066	4	-0.078	39	43
NUDC	0.001	0.052	-10000	0	-0.25	19	19
regulation of attachment of spindle microtubules to kinetochore	-0.024	0.08	-10000	0	-0.2	67	67
spindle assembly	-0.003	0.032	0.072	2	-0.091	40	42
spindle stabilization	-0.002	0.02	0.046	3	-0.054	41	44
APC/C/HCDH1	0.031	0.012	-10000	0	-10000	0	0
MKLP2/PLK1	0.014	0.051	0.096	1	-0.14	35	36
CCNB1	0.026	0.027	-10000	0	-0.029	64	64
PPP1CB	0.04	0.008	-10000	0	0	22	22
BTRC	0.04	0.007	-10000	0	0	17	17
ROCK2	-0.007	0.093	-10000	0	-0.33	38	38
TUBG1	-0.003	0.053	-10000	0	-0.21	29	29
G2/M transition of mitotic cell cycle	-0.037	0.097	-10000	0	-0.21	112	112
MLF1IP	-0.008	0.007	0.012	12	-10000	0	12
INCENP	0.04	0.005	-10000	0	0	6	6

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.045	0.04	-10000	0	-0.13	19	19
VLDLR	0.032	0.017	-10000	0	0	121	121
CRKL	0.038	0.01	-10000	0	0	36	36
LRPAP1	0.036	0.014	-10000	0	0	72	72
FYN	0.034	0.016	-10000	0	0	94	94
ITGA3	0.034	0.016	-10000	0	0	98	98
RELN/VLDLR/Fyn	0.033	0.067	-10000	0	-0.13	53	53
MAPK8IP1/MKK7/MAP3K11/JNK1	0.091	0.062	-10000	0	-0.11	18	18
AKT1	0.003	0.072	-10000	0	-0.17	54	54
MAP2K7	0.038	0.011	-10000	0	0	41	41
RAPGEF1	0.039	0.009	-10000	0	0	26	26
DAB1	0.04	0.008	-10000	0	0	21	21
RELN/LRP8/DAB1	0.059	0.038	-10000	0	-0.1	6	6
LRPAP1/LRP8	0.041	0.051	-10000	0	-0.14	35	35
RELN/LRP8/DAB1/Fyn	0.065	0.055	-10000	0	-0.1	33	33
DAB1/alpha3/beta1 Integrin	0.029	0.082	-10000	0	-0.18	12	12
long-term memory	0.069	0.069	-10000	0	-0.11	32	32
DAB1/LIS1	0.058	0.081	-10000	0	-0.11	56	56
DAB1/CRLK/C3G	0.046	0.072	-10000	0	-0.18	2	2
PIK3CA	0.029	0.019	-10000	0	0	166	166
DAB1/NCK2	0.064	0.081	-10000	0	-0.18	2	2
ARHGEF2	0.038	0.011	-10000	0	0	39	39
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.033	0.017	-10000	0	0	111	111
CDK5R1	0.038	0.011	-10000	0	0	40	40
RELN	0.034	0.016	-10000	0	0	96	96
PIK3R1	0.034	0.016	-10000	0	0	99	99
RELN/LRP8/Fyn	0.046	0.056	-10000	0	-0.12	34	34
GRIN2A/RELN/LRP8/DAB1/Fyn	0.073	0.069	-10000	0	-0.11	35	35
MAPK8	0.039	0.009	-10000	0	0	29	29
RELN/VLDLR/DAB1	0.043	0.054	-10000	0	-0.1	38	38
ITGB1	0.038	0.01	-10000	0	0	36	36
MAP1B	-0.002	0.062	0.21	21	-0.2	4	25
RELN/LRP8	0.05	0.054	-10000	0	-0.12	29	29
GRIN2B/RELN/LRP8/DAB1/Fyn	0.077	0.067	-10000	0	-0.11	29	29
PI3K	0.023	0.06	-10000	0	-0.15	44	44
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.03	0.065	-10000	0	-0.14	68	68
RAP1A	-0.008	0.088	0.28	21	-10000	0	21
PAFAH1B1	0.038	0.012	-10000	0	0	49	49
MAPK8IP1	0.039	0.009	-10000	0	0	30	30
CRLK/C3G	0.055	0.019	-10000	0	-10000	0	0
GRIN2B	0.037	0.013	-10000	0	0	59	59
NCK2	0.041	0.004	-10000	0	0	6	6
neuron differentiation	0.022	0.059	0.17	2	-0.22	9	11
neuron adhesion	-0.016	0.097	0.27	26	-0.25	1	27
LRP8	0.039	0.01	-10000	0	0	35	35
GSK3B	-0.002	0.074	0.18	7	-0.26	13	20
RELN/VLDLR/DAB1/Fyn	0.05	0.067	-10000	0	-0.11	52	52
MAP3K11	0.04	0.007	-10000	0	0	14	14
RELN/VLDLR/DAB1/P13K	-0.003	0.066	-10000	0	-0.16	57	57
CDK5	0.036	0.014	-10000	0	0	69	69
MAPT	-0.004	0.074	0.74	5	-10000	0	5
neuron migration	-0.001	0.088	0.26	15	-0.24	13	28
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.022	0.058	0.17	2	-0.2	10	12
RELN/VLDLR	0.053	0.072	-10000	0	-0.11	60	60

×

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	-0.031	0.2	0.33	23	-0.98	21	44
VDR	0.038	0.011	-10000	0	0	43	43
FAM120B	0	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.022	0.092	-10000	0	-0.23	53	53
RXRs/LXRs/DNA/Oxysterols	0.012	0.13	-10000	0	-0.34	55	55
MED1	0	0	-10000	0	-10000	0	0
mol:9cRA	0.001	0.015	0.037	2	-0.045	48	50
RARs/THRs/DNA/Src-1	-0.004	0.093	-10000	0	-0.26	34	34
RXRs/NUR77	0.074	0.071	-10000	0	-0.11	38	38
RXRs/PPAR	0.014	0.059	-10000	0	-0.17	20	20
NCOR2	0.039	0.01	-10000	0	0	31	31
VDR/VDR/Vit D3	0.023	0.031	-10000	0	-0.12	22	22
RARs/VDR/DNA/Vit D3	0.065	0.068	-10000	0	-0.11	59	59
RARA	0.039	0.01	-10000	0	0	31	31
NCOA1	0.04	0.008	-10000	0	0	22	22
VDR/VDR/DNA	0.038	0.011	-10000	0	0	43	43
RARs/RARs/DNA/9cRA	0.05	0.053	-10000	0	-0.1	46	46
RARG	0.039	0.009	-10000	0	0	26	26
RPS6KB1	-0.012	0.11	0.56	9	-0.4	21	30
RARs/THRs/DNA/SMRT	-0.002	0.088	-10000	0	-0.17	102	102
THRA	0.039	0.01	-10000	0	0	34	34
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.023	0.031	-10000	0	-0.12	22	22
RXRs/PPAR/9cRA/PGJ2/DNA	0.063	0.077	0.29	10	-0.15	33	43
NR1H4	0.04	0.006	-10000	0	0	11	11
RXRs/LXRs/DNA	0.092	0.1	-10000	0	-0.19	37	37
NR1H2	0.034	0.031	-10000	0	-0.058	50	50
NR1H3	0.035	0.034	-10000	0	-0.063	53	53
RXRs/VDR/DNA/Vit D3	0.071	0.07	-10000	0	-0.1	47	47
NR4A1	0.034	0.016	-10000	0	0	98	98
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.02	0.043	-10000	0	-0.14	10	10
RXRG	0.031	0.03	-10000	0	-0.055	43	43
RXR alpha/CCPG	0.025	0.022	-10000	0	-0.038	40	40
RXRA	0.034	0.031	-10000	0	-0.056	47	47
RXRB	0.036	0.033	-10000	0	-0.06	56	56
THRB	0.033	0.016	-10000	0	0	107	107
PPARG	0.039	0.01	-10000	0	0	32	32
PPARD	0.04	0.006	-10000	0	0	13	13
TNF	0.004	0.13	-10000	0	-0.52	8	8
mol:Oxysterols	0	0.014	-10000	0	-0.04	57	57
cholesterol transport	0.013	0.13	-10000	0	-0.34	55	55
PPARA	0.032	0.017	-10000	0	0	126	126
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.036	0.014	-10000	0	0	75	75
RXRs/NUR77/BCL2	0.019	0.045	-10000	0	-0.13	24	24
SREBF1	0.004	0.12	-10000	0	-0.35	44	44
RXRs/RXRs/DNA/9cRA	0.063	0.077	0.29	10	-0.15	33	43
ABCA1	-0.045	0.26	-10000	0	-0.82	53	53
RARs/THRs	0.068	0.091	-10000	0	-0.12	81	81
RXRs/FXR	0.085	0.067	-10000	0	-0.11	32	32
BCL2	0.036	0.014	-10000	0	0	67	67

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.05	0.021	-10000	0	-0.11	5	5
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.039	0.01	-10000	0	0	32	32
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.034	0.016	-10000	0	0	94	94
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.036	0.013	-10000	0	0	65	65
RAC1-CDC42/GTP/PAK family	0.007	0.04	-10000	0	-0.14	27	27
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.037	0.012	-10000	0	0	51	51
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.04	0.007	-10000	0	0	14	14
FYN	0.034	0.016	-10000	0	0	94	94
MAP3K12	0.04	0.006	-10000	0	0	13	13
FGR	0.04	0.007	-10000	0	0	15	15
p38 alpha/TAB1	-0.002	0.12	0.21	1	-0.26	60	61
PRKG1	0.039	0.009	-10000	0	0	30	30
DUSP8	0.039	0.009	-10000	0	0	30	30
PGK/cGMP/p38 alpha	-0.007	0.12	0.19	1	-0.26	61	62
apoptosis	-0.003	0.12	0.2	1	-0.25	60	61
RAL/GTP	0.046	0.036	-10000	0	-0.11	24	24
LYN	0.035	0.015	-10000	0	0	83	83
DUSP1	0.026	0.02	-10000	0	0	196	196
PAK1	0.036	0.013	-10000	0	0	65	65
SRC	0.039	0.009	-10000	0	0	28	28
RAC1/OSM/MEKK3/MKK3	0.091	0.038	-10000	0	-0.11	1	1
TRAF6	0.04	0.008	-10000	0	0	19	19
RAC1	0.039	0.009	-10000	0	0	28	28
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.041	0.005	-10000	0	0	9	9
RAC1-CDC42/GTP	0.05	0.02	-10000	0	-0.14	3	3
MAPK11	-0.032	0.13	0.21	1	-0.28	72	73
BLK	0.033	0.017	-10000	0	0	114	114
HCK	0.036	0.013	-10000	0	0	65	65
MAP2K3	0.038	0.011	-10000	0	0	43	43
DUSP16	0.036	0.014	-10000	0	0	75	75
DUSP10	0.034	0.016	-10000	0	0	102	102
TRAF6/MEKK3	0.048	0.021	-10000	0	-0.097	8	8
MAP3K7IP1	0.037	0.012	-10000	0	0	51	51
MAPK14	-0.015	0.12	0.2	2	-0.28	63	65
positive regulation of innate immune response	-0.028	0.14	0.23	2	-0.33	65	67
LCK	0.039	0.009	-10000	0	0	25	25
p38alpha-beta/MKP7	-0.019	0.14	-10000	0	-0.32	63	63
p38alpha-beta/MKP5	-0.023	0.15	-10000	0	-0.31	72	72
PGK/cGMP	0.029	0.007	-10000	0	-10000	0	0
PAK2	0.033	0.017	-10000	0	0	111	111
p38alpha-beta/MKP1	-0.029	0.14	0.26	1	-0.33	66	67
CDC42	0.04	0.007	-10000	0	0	18	18
RALB	0.039	0.009	-10000	0	0	25	25
RALA	0.04	0.008	-10000	0	0	19	19
PAK3	0.037	0.013	-10000	0	0	60	60

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.031	0.18	-10000	0	-0.5	23	23
RAD9A	0.041	0.004	-10000	0	0	5	5
AP1	0.002	0.083	-10000	0	-0.15	113	113
IFNAR2	0.029	0.028	-10000	0	-0.033	74	74
AKT1	0.012	0.037	-10000	0	-0.15	5	5
ER alpha/Oestrogen	0.012	0.043	-10000	0	-0.12	42	42
NFX1/SIN3/HDAC complex	0.002	0.079	-10000	0	-0.27	26	26
EGF	0.038	0.011	-10000	0	0	38	38
SMG5	0	0	-10000	0	-10000	0	0
SMG6	0	0	-10000	0	-10000	0	0
SP3/HDAC2	0.044	0.043	-10000	0	-0.13	6	6
TERT/c-Abl	-0.021	0.18	-10000	0	-0.47	25	25
SAP18	0.039	0.009	-10000	0	0	24	24
MRN complex	0.048	0.071	-10000	0	-0.15	50	50
WT1	0.029	0.027	-10000	0	-0.033	71	71
WRN	0.033	0.016	-10000	0	0	108	108
SP1	0.031	0.03	-10000	0	-0.041	77	77
SP3	0.04	0.008	-10000	0	-0.005	12	12
TERF2IP	0.037	0.013	-10000	0	0	61	61
Telomerase/Nucleolin	-0.019	0.18	-10000	0	-0.44	31	31
Mad/Max	0.054	0.025	-10000	0	-10000	0	0
TERT	-0.035	0.18	-10000	0	-0.51	22	22
CCND1	-0.11	0.37	-10000	0	-0.96	81	81
MAX	0.04	0.008	-10000	0	-0.005	14	14
RBBP7	0.039	0.009	-10000	0	0	25	25
RBBP4	0.038	0.011	-10000	0	0	40	40
TERF2	0.036	0.02	0.094	43	0	55	98
PTGES3	0.037	0.012	-10000	0	0	55	55
SIN3A	0.039	0.009	-10000	0	0	30	30
Telomerase/911	0.022	0.078	-10000	0	-0.28	20	20
CDKN1B	0	0.083	0.19	8	-0.32	21	29
RAD1	0.037	0.012	-10000	0	0	51	51
XRCC5	0.038	0.011	-10000	0	0	41	41
XRCC6	0.036	0.014	-10000	0	0	69	69
SAP30	0.038	0.011	-10000	0	0	46	46
TRF2/PARP2	0.049	0.035	-10000	0	-0.13	10	10
UBE3A	0.038	0.011	-10000	0	0	35	35
JUN	0.035	0.015	-10000	0	-0.03	2	2
E6	-0.001	0.004	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.022	0.022	-10000	0	-0.12	2	2
FOS	0.025	0.02	-10000	0	-0.001	205	205
IFN-gamma/IRF1	0.024	0.081	-10000	0	-0.15	81	81
PARP2	0.038	0.011	-10000	0	0	40	40
BLM	0.036	0.013	-10000	0	0	66	66
Telomerase	0.003	0.062	-10000	0	-0.26	19	19
IRF1	0.029	0.04	-10000	0	-0.14	20	20
ESR1	0.034	0.015	-10000	0	0	91	91
KU/TER	0.04	0.056	-10000	0	-0.16	33	33
ATM/TRF2	0.038	0.056	-10000	0	-0.14	41	41
ubiquitin-dependent protein catabolic process	0.003	0.084	0.18	4	-0.26	27	31
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.002	0.085	0.18	4	-0.26	27	31
HDAC1	0.037	0.012	-10000	0	0	49	49
HDAC2	0.03	0.03	-10000	0	-0.04	74	74
ATM	0.005	0.065	-10000	0	-0.24	33	33
SMAD3	-0.012	0.016	0.025	70	-10000	0	70
ABL1	0.039	0.01	-10000	0	0	32	32
MXD1	0.04	0.008	-10000	0	-0.002	16	16
MRE11A	0.038	0.012	-10000	0	0	49	49
HUS1	0.04	0.006	-10000	0	0	10	10
RPS6KB1	0.038	0.01	-10000	0	0	37	37
TERT/NF kappa B1/14-3-3	-0.007	0.18	-10000	0	-0.49	18	18
NR2F2	0.039	0.012	-10000	0	0	34	34
MAPK3	-0.016	0.014	0.021	50	-0.039	8	58
MAPK1	-0.016	0.014	0.021	45	-0.039	6	51
TGFB1/TGF beta receptor Type II	0.036	0.014	-10000	0	0	69	69
NFKB1	0.036	0.013	-10000	0	0	66	66
HNRNPC	0	0	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.005	0.065	-10000	0	-0.24	33	33
NBN	0.035	0.015	-10000	0	0	87	87
EGFR	0.036	0.014	-10000	0	0	67	67
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	0.041	0.051	-10000	0	-0.14	35	35
MYC	0.023	0.021	-10000	0	0	245	245
IL2	0.03	0.031	-10000	0	-0.042	77	77
KU	0.04	0.056	-10000	0	-0.16	33	33
RAD50	0.039	0.01	-10000	0	0	35	35
HSP90AA1	0	0	-10000	0	-10000	0	0
TGFB1	0.036	0.014	-10000	0	0	69	69
TRF2/BLM	0.045	0.042	-10000	0	-0.13	20	20
FRAP1	0.039	0.009	-10000	0	0	28	28
KU/TERT	-0.015	0.19	-10000	0	-0.48	25	25
SP1/HDAC2	0.043	0.05	-10000	0	-0.11	16	16
PINX1	0.032	0.017	-10000	0	0	117	117
Telomerase/EST1A	-0.025	0.16	-10000	0	-0.43	30	30
Smad3/Myc	0.016	0.038	-10000	0	-0.14	18	18
911 complex	0.072	0.034	-10000	0	-0.12	8	8
IFNG	0.034	0.035	0.11	2	-0.11	24	26
Telomerase/PinX1	-0.026	0.17	-10000	0	-0.43	30	30
Telomerase/AKT1/mTOR/p70S6K	0.001	0.096	-10000	0	-0.26	36	36
SIN3B	0.036	0.014	-10000	0	0	67	67
YWHAE	0.037	0.013	-10000	0	0	58	58
Telomerase/EST1B	-0.025	0.16	-10000	0	-0.43	30	30
response to DNA damage stimulus	0	0.035	0.1	3	-0.1	49	52
MRN complex/TRF2/Rap1	0.067	0.08	-10000	0	-0.14	37	37
TRF2/WRN	0.04	0.041	-10000	0	-0.11	23	23
Telomerase/hnRNP C1/C2	-0.025	0.16	-10000	0	-0.43	30	30
E2F1	0.03	0.027	-10000	0	-0.033	73	73
ZNFX1	0	0.001	-10000	0	-10000	0	0
PIF1	0	0	-10000	0	-10000	0	0
NCL	0.039	0.009	-10000	0	0	29	29
DKC1	0.04	0.008	-10000	0	0	20	20
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.012	0.011	0.016	40	-10000	0	40
RAS family/GTP	0.023	0.1	0.23	1	-0.21	28	29
NFATC4	-0.011	0.09	0.27	26	-0.18	4	30
ERBB2IP	0.036	0.015	-10000	0	-0.003	64	64
HSP90 (dimer)	0	0	-10000	0	-10000	0	0
mammary gland morphogenesis	0.001	0.08	0.2	15	-0.15	51	66
JUN	0.012	0.088	0.22	12	-10000	0	12
HRAS	0.039	0.01	-10000	0	0	31	31
DOCK7	-0.02	0.084	0.21	22	-0.21	10	32
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.041	0.078	0.21	25	-0.12	62	87
AKT1	-0.005	0.012	0.021	39	-10000	0	39
BAD	-0.014	0.007	0.011	20	-10000	0	20
MAPK10	-0.003	0.078	0.21	35	-0.15	2	37
mol:GTP	0	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.003	0.086	0.21	15	-0.16	49	64
RAF1	0.011	0.11	0.25	22	-0.23	27	49
ErbB2/ErbB3/neuregulin 2	0.028	0.071	0.19	30	-0.12	70	100
STAT3	-0.023	0.25	-10000	0	-0.91	38	38
cell migration	-0.003	0.081	0.22	33	-0.18	10	43
mol:PI-3-4-5-P3	-0.001	0.002	0.016	1	-10000	0	1
cell proliferation	-0.023	0.23	0.41	3	-0.54	54	57
FOS	-0.029	0.22	0.33	10	-0.4	124	134
NRAS	0.039	0.009	-10000	0	0	30	30
mol:Ca2+	0.001	0.08	0.2	15	-0.15	51	66
MAPK3	-0.006	0.19	0.36	5	-0.47	41	46
MAPK1	-0.016	0.19	0.36	4	-0.47	47	51
JAK2	-0.019	0.081	0.24	14	-0.23	6	20
NF2	0.005	0.076	-10000	0	-0.69	6	6
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0	0.073	0.18	4	-0.17	62	66
NRG1	0.036	0.014	-10000	0	0	74	74
GRB2/SOS1	0.047	0.044	-10000	0	-0.14	24	24
MAPK8	-0.017	0.11	0.24	5	-0.22	71	76
MAPK9	-0.007	0.077	0.21	32	-0.16	4	36
ERBB2	-0.024	0.04	0.26	9	-10000	0	9
ERBB3	0.031	0.018	-10000	0	0	134	134
SHC1	0.04	0.008	-10000	0	0	23	23
RAC1	0.039	0.009	-10000	0	0	28	28
apoptosis	0.005	0.025	0.18	1	-0.21	6	7
STAT3 (dimer)	-0.019	0.24	-10000	0	-0.89	38	38
RNF41	-0.016	0.015	0.048	10	-10000	0	10
FRAP1	-0.014	0.008	0.011	20	-10000	0	20
RAC1-CDC42/GTP	-0.029	0.056	0.088	29	-0.14	44	73
ErbB2/ErbB2/HSP90 (dimer)	-0.023	0.015	0.019	7	-0.12	5	12
CHRNA1	0.01	0.15	0.35	4	-0.35	33	37
myelination	-0.004	0.11	0.29	38	-0.21	2	40
PPP3CB	-0.016	0.082	0.2	25	-0.2	4	29
KRAS	0.034	0.016	-10000	0	0	95	95
RAC1-CDC42/GDP	0.027	0.097	0.21	1	-0.17	64	65
NRG2	0.041	0.005	-10000	0	0	8	8
mol:GDP	0	0.072	0.18	4	-0.17	62	66
SOS1	0.037	0.012	-10000	0	0	51	51
MAP2K2	-0.002	0.1	0.21	35	-0.22	43	78
SRC	0.039	0.009	-10000	0	0	28	28
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.019	0.086	0.24	15	-0.2	10	25
MAP2K1	-0.01	0.19	0.38	1	-0.5	32	33
heart morphogenesis	0.001	0.08	0.2	15	-0.15	51	66
RAS family/GDP	0.032	0.1	0.23	1	-0.18	48	49
GRB2	0.04	0.008	-10000	0	0	21	21
PRKACA	0.008	0.079	-10000	0	-0.72	6	6
CHRNE	0.009	0.024	0.084	8	-10000	0	8
HSP90AA1	0	0	-10000	0	-10000	0	0
activation of caspase activity	0.005	0.012	-10000	0	-0.021	39	39
nervous system development	0.001	0.08	0.2	15	-0.15	51	66
CDC42	0.04	0.007	-10000	0	0	18	18

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.036	0.027	0.081	2	-0.069	29	31
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.003	0.12	0.26	3	-0.27	57	60
ERC1	0	0	-10000	0	-10000	0	0
RIP2/NOD2	0.014	0.041	-10000	0	-0.12	41	41
NFKBIA	-0.036	0.063	0.21	3	-0.27	29	32
BIRC2	0.036	0.014	-10000	0	0	72	72
IKBKB	0.038	0.011	-10000	0	0	41	41
RIPK2	0.032	0.017	-10000	0	0	119	119
IKBKG	-0.003	0.11	-10000	0	-0.29	49	49
IKK complex/A20	0.035	0.12	-10000	0	-0.31	30	30
NEMO/A20/RIP2	0.032	0.017	-10000	0	0	119	119
XPO1	0.039	0.01	-10000	0	0	35	35
NEMO/ATM	0.006	0.12	-10000	0	-0.35	36	36
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.04	0.008	-10000	0	0	21	21
Exportin 1/RanGTP	0.045	0.035	-10000	0	-0.11	24	24
IKK complex/ELKS	0.008	0.11	-10000	0	-0.28	47	47
BCL10/MALT1/TRAF6	0.065	0.047	-10000	0	-0.12	20	20
NOD2	0	0	-10000	0	-10000	0	0
NFKB1	0.033	0.027	-10000	0	-0.071	25	25
RELA	0.036	0.028	0.08	3	-0.068	33	36
MALT1	0.036	0.014	-10000	0	0	70	70
cIAP1/UbcH5C	0.04	0.053	-10000	0	-0.14	39	39
ATM	0.036	0.014	-10000	0	0	69	69
TNF/TNFR1A	0.047	0.038	-10000	0	-0.13	16	16
TRAF6	0.04	0.008	-10000	0	0	19	19
PRKCA	0.035	0.015	-10000	0	0	86	86
CHUK	0.038	0.011	-10000	0	0	46	46
UBE2D3	0.039	0.009	-10000	0	0	30	30
TNF	0.04	0.008	-10000	0	0	22	22
NF kappa B1 p50/RelA	0.058	0.08	-10000	0	-0.15	60	60
BCL10	0.041	0.005	-10000	0	0	8	8
proteasomal ubiquitin-dependent protein catabolic process	-0.035	0.063	0.21	3	-0.27	29	32
beta TrCP1/SCF ubiquitin ligase complex	0.036	0.027	0.081	2	-0.069	29	31
TNFRSF1A	0.036	0.014	-10000	0	0	72	72
IKK complex	0.022	0.13	-10000	0	-0.3	47	47
CYLD	0.038	0.011	-10000	0	0	46	46
IKK complex/PKC alpha	0.023	0.13	-10000	0	-0.32	39	39

×

Regulation of Androgen receptor activity

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
HDAC1	-0.018	0.007	-10000	0	-10000	0	0
SMARCC1	-0.01	0.17	-10000	0	-1.1	12	12
REL	0.039	0.007	-10000	0	0	15	15
HDAC7	-0.049	0.088	0.17	7	-0.22	73	80
JUN	0.036	0.014	-10000	0	0	76	76
EP300	0.036	0.014	-10000	0	0	69	69
KAT2B	0	0	-10000	0	-10000	0	0
KAT5	0	0	-10000	0	-10000	0	0
MAPK14	-0.014	0.018	0.038	6	-0.053	1	7
FOXO1	0	0	-10000	0	-10000	0	0
T-DHT/AR	-0.005	0.12	0.26	2	-0.22	86	88
MAP2K6	0.028	0.025	-10000	0	-0.012	146	146
BRM/BAF57	0.031	0.06	-10000	0	-0.13	55	55
MAP2K4	0.03	0.024	-10000	0	-0.015	115	115
SMARCA2	0.032	0.018	-10000	0	-10000	0	0
PDE9A	-0.087	0.32	-10000	0	-0.83	82	82
NCOA2	0.037	0.013	-10000	0	0	60	60
CEBPA	0.037	0.012	-10000	0	0	54	54
EHMT2	0.041	0.007	-10000	0	0	14	14
cell proliferation	-0.024	0.12	0.28	10	-0.31	36	46
NR0B1	0.038	0.01	-10000	0	0	38	38
EGR1	0.027	0.02	-10000	0	0	188	188
RXRs/9cRA	0.063	0.035	-10000	0	-0.1	3	3
AR/RACK1/Src	-0.018	0.087	0.21	24	-0.22	21	45
AR/GR	-0.014	0.091	0.2	2	-0.19	85	87
GNB2L1	0.039	0.009	-10000	0	0	30	30
PKN1	0.034	0.016	-10000	0	0	96	96
RCHY1	0.036	0.014	-10000	0	0	67	67
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	-0.014	0.02	0.042	4	-0.06	2	6
T-DHT/AR/TIF2/CARM1	0.002	0.085	0.23	2	-0.22	24	26
SRC	-0.021	0.058	0.17	29	-0.15	7	36
NR3C1	0.038	0.011	-10000	0	0	42	42
KLK3	0.003	0.074	-10000	0	-10000	0	0
APPBP2	0.029	0.027	-10000	0	-0.033	67	67
TRIM24	0.039	0.011	-10000	0	0	39	39
T-DHT/AR/TIP60	-0.035	0.059	0.075	3	-0.16	59	62
TMPRSS2	0.014	0.1	-10000	0	-0.55	10	10
RXRG	0.035	0.015	-10000	0	0	81	81
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	0.038	0.011	-10000	0	0	43	43
RXRB	0.041	0.005	-10000	0	0	8	8
CARM1	0.036	0.014	-10000	0	0	71	71
NR2C2	0.04	0.007	-10000	0	0	14	14
KLK2	-0.006	0.071	0.22	1	-0.28	8	9
AR	-0.019	0.074	0.14	5	-0.19	65	70
SENP1	0.04	0.008	-10000	0	0	19	19
HSP90AA1	0	0	-10000	0	-10000	0	0
MDM2	0.037	0.01	-10000	0	0	36	36
SRY	0.04	0.002	-10000	0	0	2	2
GATA2	0.039	0.01	-10000	0	0	31	31
MYST2	0.04	0.008	-10000	0	0	20	20
HOXB13	0.039	0.011	-10000	0	-10000	0	0
T-DHT/AR/RACK1/Src	-0.019	0.088	0.21	24	-0.23	21	45
positive regulation of transcription	0.039	0.01	-10000	0	0	31	31
DNAJA1	0.03	0.026	-10000	0	-0.033	67	67
proteasomal ubiquitin-dependent protein catabolic process	-0.008	0.083	-10000	0	-0.26	49	49
NCOA1	0.042	0.032	0.12	1	-0.18	10	11
SPDEF	0.037	0.014	-10000	0	0	72	72
T-DHT/AR/TIF2	-0.017	0.093	0.2	5	-0.26	43	48
T-DHT/AR/Hsp90	-0.035	0.059	0.076	3	-0.16	59	62
GSK3B	0.039	0.008	-10000	0	0	23	23
NR2C1	0.038	0.01	-10000	0	0	33	33
mol:T-DHT	-0.025	0.046	0.19	6	-0.16	8	14
SIRT1	0.04	0.007	-10000	0	0	16	16
ZMIZ2	-0.001	0.001	-10000	0	-0.012	1	1
POU2F1	0.032	0.057	0.12	2	-0.11	73	75
T-DHT/AR/DAX-1	-0.026	0.076	0.2	11	-0.21	25	36
CREBBP	0.037	0.012	-10000	0	0	53	53
SMARCE1	0.039	0.01	-10000	0	0	35	35

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.039	0.01	-10000	0	0	31	31
EGFR	0.036	0.014	-10000	0	0	67	67
EGF/EGFR	0.046	0.057	-10000	0	-0.1	51	51
EGF/EGFR dimer/SHC/GRB2/SOS1	0.081	0.075	-10000	0	-0.11	49	49
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	0.036	0.014	-10000	0	0	75	75
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	0.038	0.01	-10000	0	0	38	38
EGF/EGFR dimer/SHC	0.059	0.054	-10000	0	-0.12	34	34
mol:GDP	0.073	0.071	-10000	0	-0.11	49	49
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0.034	0.015	-10000	0	0	89	89
GRB2/SOS1	0.047	0.044	-10000	0	-0.14	24	24
HRAS/GTP	0.048	0.06	-10000	0	-0.11	49	49
SHC1	0.039	0.008	-10000	0	0	23	23
HRAS/GDP	0.068	0.072	-10000	0	-0.11	46	46
FRAP1	-0.016	0.074	0.2	39	-0.18	4	43
EGF/EGFR dimer	0.041	0.05	-10000	0	-0.13	35	35
SOS1	0.037	0.012	-10000	0	0	51	51
GRB2	0.04	0.008	-10000	0	0	21	21
ETA receptor/Endothelin-1	0.038	0.046	-10000	0	-0.14	24	24

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.058	0.1	0.3	20	-0.26	15	35
PDGFB-D/PDGFRB/SLAP	0.033	0.038	-10000	0	-0.13	10	10
PDGFB-D/PDGFRB/APS/CBL	0.047	0.024	-10000	0	-0.11	4	4
AKT1	0.033	0.11	0.25	53	-0.18	1	54
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.043	0.095	0.27	18	-0.3	13	31
PIK3CA	0.029	0.019	-10000	0	0	166	166
FGR	0.022	0.09	0.23	17	-0.39	12	29
mol:Ca2+	0.025	0.09	0.25	15	-0.34	13	28
MYC	0.001	0.28	0.33	23	-0.66	71	94
SHC1	0.039	0.008	-10000	0	0	23	23
HRAS/GDP	0.039	0.057	0.18	43	-0.1	12	55
LRP1/PDGFRB/PDGFB	0.053	0.056	-10000	0	-0.12	35	35
GRB10	0.04	0.008	-10000	0	0	22	22
PTPN11	0.039	0.009	-10000	0	0	29	29
GO:0007205	0.024	0.09	0.25	15	-0.34	13	28
PTEN	0.038	0.01	-10000	0	0	36	36
GRB2	0.04	0.008	-10000	0	0	21	21
GRB7	0.037	0.013	-10000	0	0	57	57
PDGFB-D/PDGFRB/SHP2	0.046	0.042	-10000	0	-0.14	21	21
PDGFB-D/PDGFRB/GRB10	0.05	0.034	-10000	0	-0.15	9	9
cell cycle arrest	0.033	0.038	-10000	0	-0.13	10	10
HRAS	0.039	0.01	-10000	0	0	31	31
HIF1A	0.019	0.099	0.23	49	-0.2	5	54
GAB1	0.022	0.1	0.27	11	-0.28	24	35
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.024	0.11	0.25	44	-0.25	29	73
PDGFB-D/PDGFRB	0.055	0.051	-10000	0	-0.12	6	6
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.047	0.04	-10000	0	-0.13	18	18
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.048	0.12	0.29	23	-0.24	40	63
positive regulation of MAPKKK cascade	0.046	0.042	-10000	0	-0.14	21	21
PIK3R1	0.034	0.016	-10000	0	0	99	99
mol:IP3	0.025	0.091	0.25	15	-0.35	13	28
E5	0	0.002	-10000	0	-10000	0	0
CSK	0.038	0.011	-10000	0	-0.005	29	29
PDGFB-D/PDGFRB/GRB7	0.046	0.036	-10000	0	-0.14	11	11
SHB	0.04	0.006	-10000	0	0	11	11
BLK	-0.039	0.16	0.26	3	-0.37	91	94
PTPN2	0.039	0.014	-10000	0	-0.013	34	34
PDGFB-D/PDGFRB/SNX15	0.053	0.025	-10000	0	-0.14	3	3
BCAR1	0.036	0.013	-10000	0	0	65	65
VAV2	0.007	0.13	0.27	16	-0.31	51	67
CBL	0.04	0.008	-10000	0	0	20	20
PDGFB-D/PDGFRB/DEP1	0.046	0.04	-10000	0	-0.13	19	19
LCK	0.026	0.077	0.26	5	-0.36	7	12
PDGFRB	0.036	0.019	0.068	1	-0.006	81	82
ACP1	0.039	0.01	-10000	0	0	34	34
HCK	0.014	0.092	0.34	1	-0.47	12	13
ABL1	0.018	0.092	0.24	18	-0.23	24	42
PDGFB-D/PDGFRB/CBL	0.021	0.11	0.29	6	-0.31	25	31
PTPN1	0.035	0.017	-10000	0	-0.007	70	70
SNX15	0.041	0.004	-10000	0	0	6	6
STAT3	0.038	0.011	-10000	0	0	41	41
STAT1	0.034	0.016	-10000	0	0	102	102
cell proliferation	0.009	0.25	0.31	30	-0.59	71	101
SLA	0.028	0.019	-10000	0	0	179	179
actin cytoskeleton reorganization	0.008	0.093	0.22	62	-0.18	1	63
SRC	0.024	0.053	0.33	1	-10000	0	1
PI3K	-0.026	0.036	-10000	0	-0.12	35	35
PDGFB-D/PDGFRB/GRB7/SHC	0.061	0.044	-10000	0	-0.12	12	12
SH2B2	0	0	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.043	0.097	0.28	17	-0.31	13	30
LYN	-0.001	0.12	0.28	2	-0.42	31	33
LRP1	0.036	0.014	-10000	0	0	69	69
SOS1	0.037	0.012	-10000	0	0	51	51
STAT5B	0.039	0.009	-10000	0	0	27	27
STAT5A	0.038	0.01	-10000	0	0	36	36
NCK1-2/p130 Cas	0.073	0.074	-10000	0	-0.12	21	21
SPHK1	0.041	0.009	0.063	1	0	24	25
EDG1	0.042	0.007	0.063	1	0	11	12
mol:DAG	0.025	0.091	0.25	15	-0.35	13	28
PLCG1	0.024	0.092	0.25	15	-0.36	13	28
NHERF/PDGFRB	0.057	0.049	-10000	0	-0.12	19	19
YES1	0.003	0.12	0.26	5	-0.43	30	35
cell migration	0.056	0.049	-10000	0	-0.12	19	19
SHC/Grb2/SOS1	0.083	0.071	-10000	0	-0.13	21	21
SLC9A3R2	0.037	0.012	-10000	0	0	54	54
SLC9A3R1	0.038	0.012	-10000	0	0	49	49
NHERF1-2/PDGFRB/PTEN	0.075	0.058	-10000	0	-0.11	30	30
FYN	-0.012	0.13	0.26	3	-0.39	48	51
DOK1	0.006	0.067	0.19	52	-10000	0	52
HRAS/GTP	0.029	0.007	-10000	0	-10000	0	0
PDGFB	0.037	0.012	-10000	0	0	54	54
RAC1	-0.032	0.24	0.29	10	-0.53	76	86
PRKCD	0.006	0.067	0.19	50	-10000	0	50
FER	0.006	0.066	0.19	50	-10000	0	50
MAPKKK cascade	0	0.083	0.24	32	-0.18	4	36
RASA1	0.006	0.065	0.19	48	-10000	0	48
NCK1	0.036	0.014	-10000	0	0	70	70
NCK2	0.041	0.004	-10000	0	0	6	6
p62DOK/Csk	0.054	0.056	0.19	54	-0.11	11	65
PDGFB-D/PDGFRB/SHB	0.052	0.026	-10000	0	-0.14	3	3
chemotaxis	0.019	0.091	0.24	18	-0.23	24	42
STAT1-3-5/STAT1-3-5	0.051	0.079	-10000	0	-0.12	52	52
Bovine Papilomavirus E5/PDGFRB	0.025	0.019	-10000	0	-0.035	24	24
PTPRJ	0.039	0.01	-10000	0	0	33	33

×

JNK signaling in the CD4+ TCR 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
LAT/GRAP2/SLP76/HPK1	0.063	0.067	-10000	0	-0.11	44	44
MAP4K1	0.036	0.014	-10000	0	0	67	67
MAP3K8	0.039	0.008	-10000	0	0	24	24
PRKCB	0	0	-10000	0	-10000	0	0
DBNL	0.04	0.006	-10000	0	0	12	12
CRKL	0.038	0.01	-10000	0	0	36	36
MAP3K1	0.007	0.066	0.17	2	-0.18	45	47
JUN	-0.004	0.11	-10000	0	-0.5	21	21
MAP3K7	0.008	0.067	0.2	5	-0.22	18	23
GRAP2	0.037	0.013	-10000	0	0	56	56
CRK	0.038	0.012	-10000	0	0	49	49
MAP2K4	0	0.083	0.17	7	-0.27	26	33
LAT	0.04	0.006	-10000	0	0	11	11
LCP2	0.034	0.016	-10000	0	0	101	101
MAPK8	0.001	0.11	-10000	0	-0.54	21	21
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.019	0.068	-10000	0	-0.16	49	49
LAT/GRAP2/SLP76/HPK1/HIP-55	0.072	0.077	-10000	0	-0.11	42	42

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.017	0.14	0.26	3	-0.34	38	41
CaM/Ca2+	0.028	0.016	-10000	0	-0.12	5	5
AKT1	0.039	0.01	-10000	0	0	34	34
AKT2	0.037	0.012	-10000	0	0	54	54
STXBP4	0.038	0.011	-10000	0	0	43	43
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.004	0.14	0.25	3	-0.36	38	41
YWHAZ	0.034	0.016	-10000	0	0	96	96
CALM1	0.039	0.009	-10000	0	0	26	26
YWHAQ	0.04	0.007	-10000	0	0	18	18
TBC1D4	-0.018	0.007	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.038	0.011	-10000	0	0	46	46
YWHAB	0.038	0.011	-10000	0	0	45	45
SNARE/Synip	0.044	0.029	-10000	0	-0.11	9	9
YWHAG	0.039	0.009	-10000	0	0	25	25
ASIP	0.038	0.011	-10000	0	0	46	46
PRKCI	0.027	0.02	-10000	0	0	192	192
AS160/CaM/Ca2+	0.028	0.016	-10000	0	-0.12	5	5
RHOQ	0.039	0.009	-10000	0	0	25	25
GYS1	0.007	0.021	0.25	1	-0.17	5	6
PRKCZ	0.039	0.009	-10000	0	0	27	27
TRIP10	0.038	0.012	-10000	0	0	49	49
TC10/GTP/CIP4/Exocyst	0.046	0.029	-10000	0	-0.11	12	12
AS160/14-3-3	0.014	0.083	0.19	3	-0.27	23	26
VAMP2	0.036	0.014	-10000	0	0	69	69
SLC2A4	0.001	0.15	0.27	2	-0.4	38	40
STX4	0	0	-10000	0	-10000	0	0
GSK3B	0.022	0.024	-10000	0	-0.2	5	5
SFN	0.035	0.015	-10000	0	0	83	83
LNPEP	0.035	0.014	-10000	0	0	77	77
YWHAE	0.037	0.013	-10000	0	0	58	58

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0.039	0.009	-10000	0	0	26	26
MKNK1	0.04	0.007	-10000	0	0	15	15
mol:PIP3	-0.013	0.037	0.14	2	-0.16	15	17
FRAP1	0.028	0.11	-10000	0	-0.42	23	23
AKT1	0.023	0.086	0.17	112	-0.17	10	122
INSR	0.038	0.012	-10000	0	0	49	49
Insulin Receptor/Insulin	0.047	0.023	-10000	0	-0.11	4	4
mol:GTP	0.054	0.092	0.24	31	-0.16	11	42
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.006	0.053	-10000	0	-0.18	30	30
TSC2	0.039	0.01	-10000	0	0	35	35
RHEB/GDP	0.03	0.069	0.16	6	-0.16	15	21
TSC1	0.039	0.01	-10000	0	0	31	31
Insulin Receptor/IRS1	0.034	0.031	-10000	0	-0.23	6	6
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.016	0.074	0.19	1	-0.22	28	29
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.032	0.11	0.24	20	-0.33	26	46
MAP3K5	-0.006	0.061	0.19	5	-0.22	37	42
PIK3R1	0.034	0.016	-10000	0	0	99	99
apoptosis	-0.006	0.061	0.19	5	-0.22	37	42
mol:LY294002	0	0	0.001	3	-0.001	6	9
EIF4B	0.028	0.1	0.25	16	-0.3	26	42
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.04	0.1	0.23	16	-0.27	29	45
eIF4E/eIF4G1/eIF4A1	0.012	0.065	-10000	0	-0.26	21	21
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.027	0.052	-10000	0	-0.15	18	18
mTOR/RHEB/GTP/Raptor/GBL	0.028	0.077	0.2	20	-0.18	23	43
FKBP1A	0.038	0.011	-10000	0	0	44	44
RHEB/GTP	0.052	0.087	0.23	19	-0.16	14	33
mol:Amino Acids	0	0	0.001	3	-0.001	6	9
FKBP12/Rapamycin	0.028	0.013	-10000	0	-0.13	2	2
PDPK1	0.01	0.077	0.16	99	-0.17	11	110
EIF4E	0.039	0.01	-10000	0	0	31	31
ASK1/PP5C	0.02	0.19	-10000	0	-0.56	43	43
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.005	0.11	-10000	0	-0.56	10	10
TSC1/TSC2	0.059	0.099	0.26	31	-0.17	11	42
tumor necrosis factor receptor activity	0	0	0.001	6	-0.001	3	9
RPS6	0.039	0.01	-10000	0	0	32	32
PPP5C	0.039	0.009	-10000	0	0	27	27
EIF4G1	0.032	0.017	-10000	0	0	116	116
IRS1	0.011	0.028	-10000	0	-0.24	6	6
INS	0.039	0.009	-10000	0	0	30	30
PTEN	0.038	0.01	-10000	0	0	36	36
PDK2	0.012	0.077	0.16	100	-0.17	10	110
EIF4EBP1	-0.036	0.27	-10000	0	-1.1	35	35
PIK3CA	0.029	0.019	-10000	0	0	166	166
PPP2R5D	0.028	0.1	0.28	4	-0.38	22	26
peptide biosynthetic process	-0.014	0.029	0.19	9	-10000	0	9
RHEB	0.037	0.012	-10000	0	0	53	53
EIF4A1	0.038	0.011	-10000	0	0	42	42
mol:Rapamycin	0	0.001	0.003	51	-0.002	3	54
EEF2	-0.014	0.03	0.19	9	-10000	0	9
eIF4E/4E-BP1	-0.016	0.26	-10000	0	-0.99	35	35

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.041	0.25	0.48	1	-0.54	64	65
PCK1	-0.11	0.41	-10000	0	-1	78	78
HNF4A	-0.077	0.35	0.6	2	-0.76	89	91
KCNJ11	-0.008	0.23	-10000	0	-0.52	37	37
AKT1	0.005	0.17	-10000	0	-0.32	42	42
response to starvation	-0.015	0.043	-10000	0	-0.11	75	75
DLK1	-0.002	0.24	0.64	3	-0.53	35	38
NKX2-1	-0.002	0.15	0.35	3	-0.3	40	43
ACADM	-0.055	0.27	0.54	1	-0.59	69	70
TAT	-0.024	0.18	-10000	0	-0.53	17	17
CEBPB	0.039	0.017	-10000	0	-0.072	2	2
CEBPA	0.042	0.016	-10000	0	-0.069	2	2
TTR	0.035	0.17	0.62	2	-0.82	4	6
PKLR	-0.028	0.24	0.48	4	-0.55	45	49
APOA1	-0.13	0.48	-10000	0	-1.1	95	95
CPT1C	-0.036	0.24	-10000	0	-0.56	49	49
ALAS1	-0.005	0.16	-10000	0	-0.8	3	3
TFRC	-0.063	0.36	-10000	0	-0.86	75	75
FOXF1	0.034	0.015	-10000	0	-10000	0	0
NF1	0.038	0.02	-10000	0	-0.16	1	1
HNF1A (dimer)	0.009	0.001	-10000	0	-10000	0	0
CPT1A	-0.046	0.26	0.54	1	-0.57	66	67
HMGCS1	-0.034	0.26	0.5	3	-0.58	57	60
NR3C1	0.048	0.014	-10000	0	-10000	0	0
CPT1B	-0.034	0.23	-10000	0	-0.57	42	42
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.04	0.007	-10000	0	-10000	0	0
GCK	-0.036	0.24	0.46	1	-0.56	48	49
CREB1	0.019	0.095	-10000	0	-0.21	77	77
IGFBP1	-0.004	0.15	-10000	0	-0.49	4	4
PDX1	0.009	0.14	0.4	1	-0.29	28	29
UCP2	-0.062	0.3	0.48	5	-0.65	81	86
ALDOB	-0.007	0.23	-10000	0	-0.52	37	37
AFP	0.015	0.049	-10000	0	-10000	0	0
BDH1	-0.024	0.29	0.48	13	-0.6	64	77
HADH	-0.008	0.23	-10000	0	-0.47	57	57
F2	-0.038	0.31	-10000	0	-0.74	37	37
HNF1A	0.009	0.001	-10000	0	-10000	0	0
G6PC	0.021	0.087	-10000	0	-10000	0	0
SLC2A2	0.028	0.16	-10000	0	-0.43	1	1
INS	0.029	0.013	0.18	1	-10000	0	1
FOXA1	0.055	0.016	-10000	0	-10000	0	0
FOXA3	0.019	0.12	-10000	0	-0.2	114	114
FOXA2	0.01	0.29	-10000	0	-0.56	54	54
ABCC8	-0.008	0.23	-10000	0	-0.52	37	37
ALB	0.015	0.049	-10000	0	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.008	0.084	0.17	72	-10000	0	72
GNAI2	0.04	0.006	-10000	0	0	13	13
S1P/S1P5/G12	0.026	0.007	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.035	0.015	-10000	0	0	85	85
RhoA/GTP	0.008	0.085	-10000	0	-0.17	72	72
negative regulation of cAMP metabolic process	-0.008	0.078	-10000	0	-0.18	69	69
GNAZ	0.038	0.011	-10000	0	0	46	46
GNAI3	0.038	0.011	-10000	0	0	45	45
GNA12	0.039	0.01	-10000	0	0	33	33
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.008	0.078	-10000	0	-0.18	69	69
RhoA/GDP	0.029	0.014	-10000	0	-0.12	4	4
RHOA	0.04	0.006	-10000	0	0	13	13
GNAI1	0.034	0.015	-10000	0	0	93	93

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.038	0.01	-10000	0	0	36	36
RAS family/GTP/Tiam1	0.011	0.059	-10000	0	-0.16	38	38
NT3 (dimer)/TRKC	0.041	0.034	-10000	0	-0.13	7	7
NT3 (dimer)/TRKB	0.056	0.043	-10000	0	-0.12	8	8
SHC/Grb2/SOS1/GAB1/PI3K	-0.002	0.079	-10000	0	-0.2	56	56
RAPGEF1	0.039	0.009	-10000	0	0	26	26
BDNF	0.04	0.006	-10000	0	0	12	12
PIK3CA	0.029	0.019	-10000	0	0	166	166
DYNLT1	0.036	0.014	-10000	0	0	75	75
NTRK1	0.04	0.007	-10000	0	0	16	16
NTRK2	0.039	0.01	-10000	0	0	35	35
NTRK3	0.038	0.011	-10000	0	0	45	45
NT-4/5 (dimer)/TRKB	0.05	0.017	-10000	0	-0.085	1	1
neuron apoptosis	-0.031	0.099	0.25	27	-0.23	2	29
SHC 2-3/Grb2	0.032	0.1	0.24	2	-0.26	27	29
SHC1	0.039	0.008	-10000	0	0	23	23
SHC2	0.006	0.12	0.21	2	-0.35	47	49
SHC3	0.03	0.083	0.21	2	-0.4	13	15
STAT3 (dimer)	0.001	0.11	-10000	0	-0.26	79	79
NT3 (dimer)/TRKA	0.057	0.043	-10000	0	-0.12	8	8
RIN/GDP	0.044	0.083	0.22	18	-0.2	22	40
GIPC1	0.034	0.015	-10000	0	0	92	92
KRAS	0.034	0.016	-10000	0	0	95	95
DNAJA3	0.013	0.052	0.14	13	-0.15	10	23
RIN/GTP	0.028	0.008	-10000	0	-10000	0	0
CCND1	-0.054	0.18	-10000	0	-0.49	79	79
MAGED1	0.039	0.008	-10000	0	0	24	24
PTPN11	0.039	0.009	-10000	0	0	29	29
RICS	0.036	0.014	-10000	0	0	70	70
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.065	0.049	-10000	0	-0.12	24	24
GRB2	0.04	0.008	-10000	0	0	21	21
NGF (dimer)/TRKA/MATK	0.049	0.018	-10000	0	-10000	0	0
TRKA/NEDD4-2	0.047	0.038	-10000	0	-0.13	17	17
ELMO1	0.036	0.014	-10000	0	0	75	75
RhoG/GTP/ELMO1/DOCK1	0.035	0.046	-10000	0	-0.11	41	41
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.039	0.01	-10000	0	0	31	31
DOCK1	0.037	0.012	-10000	0	0	53	53
GAB2	0.031	0.018	-10000	0	0	136	136
RIT2	0.038	0.01	-10000	0	0	37	37
RIT1	0.037	0.012	-10000	0	0	50	50
FRS2	0.038	0.011	-10000	0	0	41	41
DNM1	0.039	0.01	-10000	0	0	33	33
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.038	0.012	-10000	0	0	49	49
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.031	0.06	0.17	9	-0.15	9	18
mol:GDP	0.039	0.11	0.26	16	-0.3	23	39
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.022	0.029	-10000	0	-0.12	18	18
RIT1/GDP	0.041	0.083	0.21	14	-0.21	24	38
TIAM1	0.036	0.013	-10000	0	0	66	66
PIK3R1	0.034	0.016	-10000	0	0	99	99
BDNF (dimer)/TRKB	0.072	0.03	-10000	0	-0.12	1	1
KIDINS220/CRKL/C3G	0.055	0.019	-10000	0	-10000	0	0
SHC/RasGAP	0.048	0.038	-10000	0	-0.13	18	18
FRS2 family/SHP2	0.065	0.049	-10000	0	-0.12	25	25
SHC/GRB2/SOS1/GAB1	0.076	0.061	-10000	0	-0.12	31	31
RIT1/GTP	0.024	0.026	-10000	0	-0.12	15	15
NT3 (dimer)	0.031	0.018	-10000	0	0	133	133
RAP1/GDP	0.03	0.073	0.18	9	-0.18	26	35
KIDINS220/CRKL	0.038	0.01	-10000	0	0	36	36
BDNF (dimer)	0.04	0.006	-10000	0	0	12	12
ubiquitin-dependent protein catabolic process	0.043	0.033	-10000	0	-0.11	17	17
Schwann cell development	-0.007	0.011	-10000	0	-0.044	11	11
EHD4	0.039	0.01	-10000	0	0	35	35
FRS2 family/GRB2/SOS1	0.079	0.059	-10000	0	-0.12	28	28
FRS2 family/SHP2/CRK family/C3G/GAB2	0.003	0.081	-10000	0	-0.21	38	38
RAP1B	0.037	0.012	-10000	0	0	54	54
RAP1A	0.039	0.01	-10000	0	0	35	35
CDC42/GTP	0.067	0.051	0.2	2	-0.11	9	11
ABL1	0.039	0.01	-10000	0	0	32	32
SH2B family/GRB2/SOS1	0.047	0.044	-10000	0	-0.14	24	24
Rap1/GTP	0.005	0.11	-10000	0	-0.27	52	52
STAT3	0.001	0.11	-10000	0	-0.26	79	79
axon guidance	0.041	0.036	-10000	0	-0.11	9	9
MAPK3	-0.014	0.031	0.19	11	-10000	0	11
MAPK1	-0.013	0.032	0.19	12	-10000	0	12
CDC42/GDP	0.046	0.086	0.22	21	-0.2	24	45
NTF3	0.031	0.018	-10000	0	0	133	133
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.05	0.019	-10000	0	-0.11	2	2
PI3K	0.023	0.06	-10000	0	-0.15	44	44
FRS3	0.04	0.008	-10000	0	0	21	21
FAIM	0.038	0.011	-10000	0	0	43	43
GAB1	0.037	0.013	-10000	0	0	58	58
RASGRF1	0.013	0.052	0.14	13	-0.15	10	23
SOS1	0.037	0.012	-10000	0	0	51	51
MCF2L	0.004	0.058	0.18	35	-0.12	7	42
RGS19	0.037	0.013	-10000	0	0	59	59
CDC42	0.04	0.007	-10000	0	0	18	18
RAS family/GTP	0.033	0.12	0.29	3	-0.35	29	32
Rac1/GDP	0.045	0.085	0.22	21	-0.2	24	45
NGF (dimer)/TRKA/GRIT	0.043	0.034	-10000	0	-0.11	19	19
neuron projection morphogenesis	-0.048	0.24	-10000	0	-0.83	39	39
NGF (dimer)/TRKA/NEDD4-2	0.043	0.033	-10000	0	-0.11	17	17
MAP2K1	-0.007	0.079	0.2	58	-0.18	3	61
NGFR	0.039	0.009	-10000	0	0	25	25
NGF (dimer)/TRKA/GIPC/GAIP	0.015	0.041	-10000	0	-0.15	23	23
RAS family/GTP/PI3K	-0.005	0.07	-10000	0	-0.19	49	49
FRS2 family/SHP2/GRB2/SOS1	0.087	0.074	-10000	0	-0.13	38	38
NRAS	0.039	0.009	-10000	0	0	30	30
GRB2/SOS1	0.047	0.044	-10000	0	-0.14	24	24
PRKCI	0.027	0.02	-10000	0	0	192	192
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.039	0.009	-10000	0	0	28	28
PRKCZ	0.039	0.009	-10000	0	0	27	27
MAPKKK cascade	0.026	0.049	-10000	0	-0.5	2	2
RASA1	0.037	0.013	-10000	0	0	56	56
TRKA/c-Abl	0.053	0.031	-10000	0	-0.13	11	11
SQSTM1	0.038	0.011	-10000	0	0	46	46
BDNF (dimer)/TRKB/GIPC	0.07	0.059	-10000	0	-0.11	23	23
NGF (dimer)/TRKA/p62/Atypical PKCs	0.045	0.068	-10000	0	-0.11	54	54
MATK	0.037	0.013	-10000	0	0	56	56
NEDD4L	0.036	0.014	-10000	0	0	74	74
RAS family/GDP	-0.01	0.039	-10000	0	-0.14	24	24
NGF (dimer)/TRKA	0.004	0.04	0.16	6	-0.15	10	16
Rac1/GTP	-0.003	0.049	-10000	0	-0.15	14	14
FRS2 family/SHP2/CRK family	0.087	0.067	-10000	0	-0.12	23	23

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.04	0.039	0.17	2	-0.15	10	12
BIRC5	0.037	0.012	-10000	0	0	52	52
NFKBIA	-0.004	0.027	0.25	1	-0.18	5	6
CPEB1	0.039	0.009	-10000	0	0	28	28
AKT1	-0.002	0.041	0.26	9	-0.17	6	15
NDEL1	0.038	0.011	-10000	0	0	40	40
Aurora A/BRCA1	0.026	0.048	0.15	2	-0.098	52	54
NDEL1/TACC3	0.045	0.051	0.17	1	-0.11	30	31
GADD45A	0.036	0.013	-10000	0	0	66	66
GSK3B	0.038	0.012	0.091	14	0	23	37
PAK1/Aurora A	0.041	0.039	0.17	2	-0.16	9	11
MDM2	0.038	0.01	-10000	0	0	36	36
JUB	0.037	0.013	-10000	0	0	62	62
TPX2	-0.015	0.009	-10000	0	-10000	0	0
TP53	-0.045	0.12	0.16	1	-0.24	134	135
DLG7	-0.002	0.026	0.25	1	-0.17	3	4
AURKAIP1	0	0	-10000	0	-10000	0	0
ARHGEF7	0.039	0.009	-10000	0	0	28	28
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.047	0.054	0.18	1	-0.12	30	31
G2/M transition of mitotic cell cycle	0.026	0.048	0.15	2	-0.098	52	54
AURKA	0.01	0.029	0.13	12	-0.2	6	18
AURKB	-0.002	0.063	-10000	0	-0.19	49	49
CDC25B	0.005	0.047	-10000	0	-0.22	19	19
G2/M transition checkpoint	0.032	0.043	0.15	2	-0.11	31	33
mRNA polyadenylation	0.038	0.033	0.15	2	-0.13	10	12
Aurora A/CPEB	0.039	0.034	0.15	2	-0.13	10	12
Aurora A/TACC1/TRAP/chTOG	0.051	0.073	-10000	0	-0.17	14	14
BRCA1	0.034	0.015	-10000	0	0	93	93
centrosome duplication	0.041	0.039	0.17	2	-0.16	9	11
regulation of centrosome cycle	0.044	0.05	0.17	1	-0.11	30	31
spindle assembly	0.049	0.072	-10000	0	-0.17	14	14
TDRD7	0.034	0.015	-10000	0	0	89	89
Aurora A/RasGAP/Survivin	0.044	0.071	0.19	1	-0.16	8	9
CENPA	0.009	0.053	-10000	0	-0.32	11	11
Aurora A/PP2A	0.044	0.038	0.17	2	-0.15	10	12
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	-0.013	0.057	0.17	4	-0.2	14	18
negative regulation of DNA binding	-0.046	0.12	0.16	1	-0.24	137	138
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.055	0.018	-10000	0	-10000	0	0
RASA1	0.037	0.013	-10000	0	0	56	56
Ajuba/Aurora A	0.032	0.043	0.15	2	-0.11	31	33
mitotic prometaphase	0.004	0.025	0.073	62	-10000	0	62
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.029	0.13	12	-0.2	6	18
TACC1	0.035	0.015	-10000	0	0	86	86
TACC3	0.033	0.016	-10000	0	0	103	103
Aurora A/Antizyme1	0.029	0.043	0.15	1	-0.1	34	35
Aurora A/RasGAP	0.041	0.04	0.17	2	-0.16	10	12
OAZ1	0.033	0.016	-10000	0	0	105	105
RAN	0.04	0.008	-10000	0	0	21	21
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.034	0.016	0.091	12	0	84	96
GIT1	0.039	0.009	-10000	0	0	25	25
GIT1/beta-PIX/PAK1	0.064	0.044	-10000	0	-0.12	16	16
Importin alpha/Importin beta/TPX2	-0.015	0.009	-10000	0	-10000	0	0
PPP2R5D	0.039	0.009	-10000	0	0	26	26
Aurora A/TPX2	0.017	0.034	0.15	1	-0.17	10	11
PAK1	0.036	0.013	-10000	0	0	65	65
CKAP5	0.038	0.011	-10000	0	0	45	45

×

p38 MAPK signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.019	0.052	-10000	0	-0.13	47	47
TRAF2/ASK1	0.044	0.033	-10000	0	-0.11	18	18
ATM	0.036	0.014	-10000	0	0	69	69
MAP2K3	-0.029	0.15	-10000	0	-0.33	84	84
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.035	0.14	0.21	2	-0.33	65	67
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.037	0.013	-10000	0	0	58	58
TXN	0.009	0.003	-10000	0	-10000	0	0
CALM1	0.039	0.009	-10000	0	0	26	26
GADD45A	0.036	0.013	-10000	0	0	66	66
GADD45B	0.034	0.015	-10000	0	0	92	92
MAP3K1	0.036	0.013	-10000	0	0	63	63
MAP3K6	0.04	0.008	-10000	0	0	19	19
MAP3K7	0.038	0.01	-10000	0	0	38	38
MAP3K4	0.038	0.011	-10000	0	0	43	43
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.048	0.039	-10000	0	-0.13	19	19
TAK1/TAB family	0.016	0.07	0.17	2	-0.28	21	23
RAC1/OSM/MEKK3	0.073	0.023	-10000	0	-0.1	1	1
TRAF2	0.039	0.01	-10000	0	0	32	32
RAC1/OSM/MEKK3/MKK3	0.002	0.14	-10000	0	-0.27	81	81
TRAF6	0.008	0.044	-10000	0	-0.2	24	24
RAC1	0.039	0.009	-10000	0	0	28	28
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.041	0.005	-10000	0	0	9	9
CCM2	0.041	0.005	-10000	0	0	9	9
CaM/Ca2+/CAMKIIB	0.052	0.017	-10000	0	-0.11	3	3
MAPK11	0.029	0.019	-10000	0	0	157	157
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.063	0.042	-10000	0	-0.1	21	21
OSM/MEKK3	0.059	0.012	-10000	0	-10000	0	0
TAOK1	0.004	0.052	-10000	0	-0.2	34	34
TAOK2	0.004	0.052	-10000	0	-0.2	34	34
TAOK3	0.001	0.058	-10000	0	-0.2	43	43
MAP3K7IP1	0.037	0.012	-10000	0	0	51	51
MAPK14	0.04	0.008	-10000	0	0	20	20
MAP3K7IP2	0.037	0.012	-10000	0	0	53	53
MAP3K5	0.037	0.013	-10000	0	0	60	60
MAP3K10	0.037	0.013	-10000	0	0	57	57
MAP3K3	0.04	0.007	-10000	0	0	14	14
TRX/ASK1	0.022	0.047	-10000	0	-0.15	34	34
GADD45/MTK1/MTK1	0.056	0.066	-10000	0	-0.1	55	55

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.038	0.01	-10000	0	0	37	37
VLDLR	0.032	0.017	-10000	0	0	121	121
LRPAP1	0.036	0.014	-10000	0	0	72	72
NUDC	0.039	0.009	-10000	0	0	25	25
RELN/LRP8	0.05	0.054	-10000	0	-0.12	29	29
CaM/Ca2+	0.028	0.016	-10000	0	-0.12	5	5
KATNA1	0.037	0.012	-10000	0	0	51	51
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.006	0.059	0.19	24	-0.19	1	25
IQGAP1/CaM	0.041	0.054	-10000	0	-0.14	43	43
DAB1	0.04	0.008	-10000	0	0	21	21
IQGAP1	0.036	0.013	-10000	0	0	66	66
PLA2G7	0.03	0.018	-10000	0	0	149	149
CALM1	0.039	0.009	-10000	0	0	26	26
DYNLT1	0.036	0.014	-10000	0	0	75	75
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.041	0.051	-10000	0	-0.14	35	35
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0	0	-10000	0	-10000	0	0
CDK5R1	0.038	0.011	-10000	0	0	40	40
LIS1/Poliovirus Protein 3A	-0.015	0.013	-10000	0	-0.13	5	5
CDK5R2	0.04	0.006	-10000	0	0	11	11
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	0.045	0.058	-10000	0	-0.12	38	38
YWHAE	0.037	0.013	-10000	0	0	58	58
NDEL1/14-3-3 E	0.028	0.076	0.25	25	-0.17	6	31
MAP1B	-0.006	0.049	0.18	3	-0.18	36	39
RAC1	0.011	0.041	-10000	0	-0.58	1	1
p35/CDK5	-0.011	0.062	0.18	23	-0.18	1	24
RELN	0.034	0.016	-10000	0	0	96	96
PAFAH/LIS1	0.025	0.027	-10000	0	-0.15	5	5
LIS1/CLIP170	-0.015	0.013	-10000	0	-0.13	5	5
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	0.02	0.075	0.19	8	-0.18	14	22
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.001	0.093	-10000	0	-0.22	60	60
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.001	0.069	0.21	32	-10000	0	32
LIS1/IQGAP1	0.03	0.026	-10000	0	-0.15	5	5
RHOA	0.011	0.043	0.12	18	-0.12	27	45
PAFAH1B1	-0.017	0.008	-10000	0	-10000	0	0
PAFAH1B3	0.034	0.016	-10000	0	0	94	94
PAFAH1B2	0.039	0.009	-10000	0	0	28	28
MAP1B/LIS1/Dynein heavy chain	0.014	0.059	0.18	1	-0.14	40	41
NDEL1/Katanin 60/Dynein heavy chain	0.034	0.084	0.28	15	-0.18	9	24
LRP8	0.039	0.01	-10000	0	0	35	35
NDEL1/Katanin 60	0.024	0.074	0.24	22	-0.17	10	32
P39/CDK5	-0.011	0.066	0.19	25	-0.18	1	26
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.033	0.025	-10000	0	-0.15	5	5
CDK5	-0.012	0.05	0.18	16	-0.18	1	17
PPP2R5D	0.039	0.009	-10000	0	0	26	26
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.012	0.011	-10000	0	-0.1	5	5
CSNK2A1	0.038	0.012	-10000	0	0	47	47
RELN/VLDLR/DAB1/LIS1	0.055	0.064	0.2	19	-0.11	36	55
RELN/VLDLR	0.053	0.072	-10000	0	-0.11	60	60
CDC42	0.01	0.047	0.12	19	-0.12	32	51

×

Ceramide signaling pathway

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
SPHK2	-0.018	0.007	0	74	-10000	0	74
MAP4K4	-0.006	0.079	-10000	0	-0.24	31	31
BAG4	0.037	0.012	-10000	0	0	55	55
PKC zeta/ceramide	0.029	0.032	-10000	0	-0.18	8	8
NFKBIA	0.036	0.013	-10000	0	0	64	64
BIRC3	0.025	0.02	-10000	0	0	210	210
BAX	0.007	0.067	-10000	0	-0.34	19	19
RIPK1	0.039	0.01	-10000	0	0	32	32
AKT1	0.002	0.12	0.69	16	-10000	0	16
BAD	-0.001	0.028	0.22	2	-0.18	7	9
SMPD1	0.008	0.059	0.16	14	-0.17	28	42
RB1	-0.003	0.043	0.2	8	-0.18	8	16
FADD/Caspase 8	-0.008	0.11	0.24	8	-0.3	43	51
MAP2K4	-0.007	0.028	-10000	0	-0.18	8	8
NSMAF	0.037	0.012	-10000	0	0	55	55
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.003	0.042	0.18	15	-0.19	8	23
EGF	0.038	0.01	-10000	0	0	38	38
mol:ceramide	0.005	0.027	-10000	0	-0.19	8	8
MADD	0.041	0.005	-10000	0	0	9	9
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.015	0.009	0	151	-10000	0	151
ASAH1	0.033	0.016	-10000	0	0	106	106
negative regulation of cell cycle	-0.003	0.043	0.2	8	-0.18	8	16
cell proliferation	0.026	0.054	0.2	11	-0.21	6	17
BID	-0.017	0.18	-10000	0	-0.65	36	36
MAP3K1	-0.002	0.027	-10000	0	-0.18	8	8
EIF2A	0.007	0.078	0.19	60	-0.22	8	68
TRADD	0.037	0.013	-10000	0	0	61	61
CRADD	0.04	0.006	-10000	0	0	10	10
MAPK3	-0.002	0.044	0.18	14	-0.21	6	20
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.007	0.048	0.18	13	-0.19	7	20
Cathepsin D/ceramide	0.028	0.032	-10000	0	-0.18	8	8
FADD	-0.005	0.082	0.22	4	-0.24	32	36
KSR1	0	0.033	0.21	5	-0.18	8	13
MAPK8	0.002	0.053	-10000	0	-0.2	15	15
PRKRA	0.003	0.046	0.2	18	-0.18	8	26
PDGFA	0.037	0.013	-10000	0	0	57	57
TRAF2	0.039	0.01	-10000	0	0	32	32
IGF1	0.035	0.014	-10000	0	0	77	77
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	0.005	0.027	-10000	0	-0.19	8	8
CTSD	0.037	0.012	-10000	0	0	55	55
regulation of nitric oxide biosynthetic process	0.044	0.049	-10000	0	-0.13	34	34
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.029	0.057	0.21	11	-0.22	6	17
PRKCD	0.037	0.012	-10000	0	0	51	51
PRKCZ	0.039	0.009	-10000	0	0	27	27
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.015	0.009	0	151	-10000	0	151
RelA/NF kappa B1	0.044	0.049	-10000	0	-0.13	34	34
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.04	0.006	-10000	0	0	11	11
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.001	0.084	-10000	0	-0.25	30	30
TNFR1A/BAG4/TNF-alpha	0.06	0.045	-10000	0	-0.11	15	15
mol:Sphingosine-1-phosphate	-0.018	0.007	0	74	-10000	0	74
MAP2K1	-0.008	0.041	0.17	15	-0.19	7	22
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.04	0.006	-10000	0	0	10	10
CYCS	0.003	0.047	-10000	0	-0.18	14	14
TNFRSF1A	0.036	0.014	-10000	0	0	72	72
NFKB1	0.036	0.013	-10000	0	0	66	66
TNFR1A/BAG4	0.045	0.037	-10000	0	-0.13	14	14
EIF2AK2	-0.003	0.055	0.18	23	-0.19	10	33
TNF-alpha/TNFR1A/FAN	0.059	0.052	-10000	0	-0.14	21	21
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.005	0.14	-10000	0	-0.4	48	48
MAP2K2	-0.005	0.04	0.18	14	-0.19	6	20
SMPD3	-0.004	0.1	0.19	4	-0.29	47	51
TNF	0.04	0.008	-10000	0	0	22	22
PKC zeta/PAR4	0.057	0.017	-10000	0	-0.13	1	1
mol:PHOSPHOCHOLINE	0.004	0.031	0.15	2	-0.14	7	9
NF kappa B1/RelA/I kappa B alpha	0.079	0.081	-10000	0	-0.12	59	59
AIFM1	0.004	0.042	0.12	1	-0.17	14	15
BCL2	0.036	0.014	-10000	0	0	67	67

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.025	0.13	0.27	1	-0.38	42	43
BAG4	0.037	0.012	-10000	0	0	55	55
BAD	-0.009	0.047	0.19	4	-0.13	30	34
NFKBIA	0.036	0.013	-10000	0	0	64	64
BIRC3	0.025	0.02	-10000	0	0	210	210
BAX	-0.008	0.045	0.17	3	-0.13	28	31
EnzymeConsortium:3.1.4.12	-0.003	0.031	0.064	2	-0.084	38	40
IKBKB	-0.025	0.13	0.22	12	-0.37	40	52
MAP2K2	-0.007	0.043	0.16	10	-0.14	8	18
MAP2K1	-0.011	0.045	0.16	10	-0.14	9	19
SMPD1	-0.003	0.036	-10000	0	-0.1	32	32
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.016	0.14	0.25	9	-0.37	43	52
MAP2K4	-0.009	0.04	-10000	0	-0.14	21	21
protein ubiquitination	-0.031	0.13	0.26	1	-0.37	42	43
EnzymeConsortium:2.7.1.37	-0.011	0.046	0.16	9	-0.16	5	14
response to UV	0	0	0.002	9	-0.002	3	12
RAF1	-0.009	0.047	0.17	10	-0.14	15	25
CRADD	0.04	0.006	-10000	0	0	10	10
mol:ceramide	-0.004	0.046	0.12	1	-0.13	37	38
I-kappa-B-alpha/RELA/p50/ubiquitin	0.041	0.042	-10000	0	-0.11	35	35
MADD	0.041	0.005	-10000	0	0	9	9
MAP3K1	-0.009	0.043	0.12	1	-0.13	33	34
TRADD	0.037	0.013	-10000	0	0	61	61
RELA/p50	0.04	0.006	-10000	0	0	10	10
MAPK3	-0.007	0.046	0.16	9	-0.17	6	15
MAPK1	-0.01	0.052	0.16	8	-0.18	15	23
p50/RELA/I-kappa-B-alpha	0.044	0.05	-10000	0	-0.14	35	35
FADD	-0.021	0.14	0.24	9	-0.37	42	51
KSR1	-0.006	0.044	0.16	5	-0.13	24	29
MAPK8	-0.015	0.044	0.18	3	-0.15	12	15
TRAF2	0.039	0.01	-10000	0	0	32	32
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	-0.034	0.13	0.26	1	-0.35	46	47
TNF R/SODD	0.045	0.037	-10000	0	-0.13	14	14
TNF	0.04	0.008	-10000	0	0	22	22
CYCS	-0.01	0.048	0.15	3	-0.14	25	28
IKBKG	-0.032	0.13	0.26	1	-0.37	39	40
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.02	0.14	-10000	0	-0.39	42	42
RELA	0.04	0.006	-10000	0	0	10	10
RIPK1	0.039	0.01	-10000	0	0	32	32
AIFM1	-0.009	0.046	0.13	6	-0.14	23	29
TNF/TNF R/SODD	0.06	0.045	-10000	0	-0.11	15	15
TNFRSF1A	0.036	0.014	-10000	0	0	72	72
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.017	0.13	-10000	0	-0.65	18	18
NSMAF	-0.017	0.14	0.24	15	-0.38	41	56
response to hydrogen peroxide	0	0	0.002	9	-0.002	3	12
BCL2	0.036	0.014	-10000	0	0	67	67

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.039	0.009	-9999	0	30	30
Syndecan-3/Src/Cortactin	0.022	0.091	-9999	-0.35	13	13
Syndecan-3/Neurocan	0.001	0.064	-9999	-0.41	12	12
POMC	0.04	0.006	-9999	0	12	12
EGFR	0.036	0.014	-9999	0	67	67
Syndecan-3/EGFR	0.032	0.075	-9999	-0.42	12	12
AGRP	0.037	0.012	-9999	0	55	55
NCSTN	0.04	0.008	-9999	0	22	22
PSENEN	0.034	0.016	-9999	0	96	96
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.035	0.014	-9999	0	79	79
APH1A	0.038	0.011	-9999	0	42	42
NCAN	0	0	-9999	-10000	0	0
long-term memory	0.042	0.081	-9999	-0.39	12	12
Syndecan-3/IL8	0.026	0.073	-9999	-0.41	12	12
PSEN1	0.039	0.01	-9999	0	31	31
Src/Cortactin	0.052	0.032	-9999	-0.13	11	11
FYN	0.034	0.016	-9999	0	94	94
limb bud formation	0.002	0.065	-9999	-0.44	11	11
MC4R	0	0	-9999	-10000	0	0
SRC	0.039	0.009	-9999	0	28	28
PTN	0.023	0.02	-9999	0	241	241
FGFR/FGF/Syndecan-3	0.002	0.065	-9999	-0.44	11	11
neuron projection morphogenesis	-0.011	0.068	-9999	-0.38	10	10
Syndecan-3/AgRP	0.034	0.073	-9999	-0.41	12	12
Syndecan-3/AgRP/MC4R	0.032	0.071	-9999	-0.4	12	12
Fyn/Cortactin	0.037	0.055	-9999	-0.13	44	44
SDC3	0.003	0.064	-9999	-0.46	10	10
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	0.026	0.072	-9999	-0.41	12	12
IL8	0.031	0.018	-9999	0	129	129
Syndecan-3/Fyn/Cortactin	0.043	0.083	-9999	-0.4	12	12
Syndecan-3/CASK	0.001	0.064	-9999	-0.41	12	12
alpha-MSH/MC4R	0.03	0.004	-9999	-10000	0	0
Gamma Secretase	0.067	0.085	-9999	-0.12	63	63

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.035	0.015	-10000	0	0	85	85
CDC42/GTP	0.009	0.084	-10000	0	-0.17	70	70
PLCG1	-0.014	0.072	-10000	0	-0.18	68	68
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.04	0.006	-10000	0	0	13	13
GNAI3	0.038	0.011	-10000	0	0	45	45
G12/G13	0.053	0.028	-10000	0	-0.13	8	8
cell migration	0.008	0.083	-10000	0	-0.17	70	70
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
MAPK3	-0.013	0.073	-10000	0	-0.18	66	66
MAPK1	-0.008	0.065	-10000	0	-0.17	58	58
S1P/S1P5/Gi	-0.008	0.078	-10000	0	-0.18	69	69
GNAI1	0.034	0.015	-10000	0	0	93	93
CDC42/GDP	0.029	0.012	-10000	0	-0.12	3	3
S1P/S1P5/G12	0.026	0.007	-10000	0	-10000	0	0
RHOA	-0.014	0.03	0.19	9	-0.17	1	10
S1P/S1P4/Gi	-0.008	0.078	-10000	0	-0.18	69	69
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.038	0.011	-10000	0	0	46	46
S1P/S1P4/G12/G13	0.046	0.023	-10000	0	-0.097	8	8
GNA12	0.039	0.01	-10000	0	0	33	33
GNA13	0.039	0.008	-10000	0	0	23	23
CDC42	0.04	0.007	-10000	0	0	18	18

×

Arf6 downstream 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.033	0.2	-10000	0	-0.8	34	34
regulation of axonogenesis	-0.002	0.048	0.24	11	-10000	0	11
myoblast fusion	-0.013	0.1	0.35	36	-10000	0	36
mol:GTP	0.016	0.066	-10000	0	-0.2	43	43
regulation of calcium-dependent cell-cell adhesion	-0.036	0.089	0.2	40	-10000	0	40
ARF1/GTP	0.037	0.059	-10000	0	-0.16	38	38
mol:GM1	0.003	0.046	-10000	0	-0.15	40	40
mol:Choline	-0.001	0.034	-10000	0	-0.14	26	26
lamellipodium assembly	-0.009	0.12	-10000	0	-0.4	44	44
MAPK3	0.009	0.083	-10000	0	-0.28	40	40
ARF6/GTP/NME1/Tiam1	0.037	0.089	-10000	0	-0.2	40	40
ARF1	0.038	0.011	-10000	0	0	45	45
ARF6/GDP	0.013	0.1	-10000	0	-0.36	36	36
ARF1/GDP	0.018	0.1	-10000	0	-0.32	40	40
ARF6	0.042	0.045	-10000	0	-0.13	33	33
RAB11A	0.04	0.008	-10000	0	0	19	19
TIAM1	0.032	0.023	-10000	0	-0.045	28	28
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.011	0.079	-10000	0	-0.28	35	35
actin filament bundle formation	-0.025	0.11	0.32	44	-10000	0	44
KALRN	0.003	0.074	-10000	0	-0.26	35	35
RAB11FIP3/RAB11A	0.054	0.026	-10000	0	-0.13	6	6
RhoA/GDP	0.026	0.11	-10000	0	-0.32	44	44
NME1	0.031	0.024	-10000	0	-0.047	33	33
Rac1/GDP	0.025	0.11	-10000	0	-0.32	44	44
substrate adhesion-dependent cell spreading	0.016	0.066	-10000	0	-0.2	43	43
cortical actin cytoskeleton organization	-0.009	0.12	-10000	0	-0.41	43	43
RAC1	0.039	0.009	-10000	0	0	28	28
liver development	0.016	0.066	-10000	0	-0.2	43	43
ARF6/GTP	0.016	0.066	-10000	0	-0.2	43	43
RhoA/GTP	0.04	0.062	-10000	0	-0.16	43	43
mol:GDP	-0.003	0.097	-10000	0	-0.34	37	37
ARF6/GTP/RAB11FIP3/RAB11A	0.057	0.065	-10000	0	-0.14	43	43
RHOA	0.04	0.006	-10000	0	0	13	13
PLD1	0.008	0.047	-10000	0	-0.17	31	31
RAB11FIP3	0.038	0.01	-10000	0	0	37	37
tube morphogenesis	-0.009	0.12	-10000	0	-0.4	44	44
ruffle organization	0.002	0.048	-10000	0	-0.24	11	11
regulation of epithelial cell migration	0.016	0.066	-10000	0	-0.2	43	43
PLD2	0.015	0.047	-10000	0	-0.15	36	36
PIP5K1A	0.002	0.048	-10000	0	-0.25	11	11
mol:Phosphatidic acid	-0.001	0.034	-10000	0	-0.14	26	26
Rac1/GTP	-0.009	0.12	-10000	0	-0.41	43	43

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.019	0.015	0.059	14	-10000	0	14
SNTA1	0.039	0.01	-10000	0	0	34	34
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.018	0.016	0.059	15	-10000	0	15
MAPK12	-0.008	0.038	0.21	4	-0.16	12	16
CCND1	-0.04	0.13	-10000	0	-0.37	70	70
p38 gamma/SNTA1	0.023	0.068	0.22	8	-0.17	28	36
MAP2K3	0.038	0.011	-10000	0	0	43	43
PKN1	0.034	0.016	-10000	0	0	96	96
G2/M transition checkpoint	-0.008	0.038	0.21	4	-0.16	12	16
MAP2K6	0.002	0.04	0.24	2	-0.17	19	21
MAPT	0	0.047	0.14	8	-0.19	13	21
MAPK13	-0.017	0.007	0	84	-10000	0	84
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.004	0.048	-10000	0	-0.2	29	29

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.036	0.016	0.078	1	-0.056	3	4
HSPA8	0.039	0.01	-10000	0	0	34	34
SMAD3/SMAD4/ER alpha	0.063	0.091	0.23	34	-0.16	18	52
AKT1	0.04	0.017	-10000	0	-0.098	5	5
GSC	0.026	0.1	-10000	0	-0.73	5	5
NKX2-5	0.038	0.018	0.082	2	-0.055	14	16
muscle cell differentiation	-0.045	0.093	0.28	11	-10000	0	11
SMAD2-3/SMAD4/SP1	0.072	0.12	-10000	0	-0.2	9	9
SMAD4	0.036	0.047	-10000	0	-0.1	11	11
CBFB	0.036	0.014	-10000	0	0	67	67
SAP18	0.039	0.008	-10000	0	0	24	24
Cbp/p300/MSG1	0.059	0.055	-10000	0	-0.14	22	22
SMAD3/SMAD4/VDR	0.077	0.099	-10000	0	-0.21	12	12
MYC	0.022	0.021	0.11	5	-0.042	2	7
CDKN2B	-0.037	0.16	-10000	0	-1.3	5	5
AP1	0.005	0.092	-10000	0	-0.22	41	41
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.006	0.12	0.19	3	-0.32	42	45
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.014	0.059	-10000	0	-0.21	26	26
SP3	0.036	0.023	0.081	1	-0.053	32	33
CREB1	0.04	0.007	-10000	0	0	17	17
FOXH1	0.028	0.025	-10000	0	-0.059	15	15
SMAD3/SMAD4/GR	0.053	0.078	-10000	0	-0.15	19	19
GATA3	0.042	0.012	-10000	0	-10000	0	0
SKI/SIN3/HDAC complex/NCoR1	0.003	0.094	-10000	0	-0.27	34	34
MEF2C/TIF2	0.062	0.1	0.22	101	-0.21	16	117
endothelial cell migration	-0.03	0.11	0.94	5	-10000	0	5
MAX	0.029	0.027	0.097	3	-0.035	77	80
RBBP7	0.039	0.009	-10000	0	0	25	25
RBBP4	0.038	0.011	-10000	0	0	40	40
RUNX2	0.038	0.011	-10000	0	0	40	40
RUNX3	0.039	0.01	-10000	0	0	33	33
RUNX1	0.039	0.01	-10000	0	0	33	33
CTBP1	0.038	0.012	-10000	0	0	49	49
NR3C1	0.026	0.027	0.097	3	-0.035	77	80
VDR	0.038	0.011	-10000	0	0	43	43
CDKN1A	0.013	0.075	-10000	0	-0.65	2	2
KAT2B	0	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.056	0.062	-10000	0	-0.22	3	3
DCP1A	0.04	0.007	-10000	0	0	17	17
SKI	0.039	0.009	-10000	0	0	29	29
SERPINE1	0.028	0.11	-10000	0	-0.95	5	5
SMAD3/SMAD4/ATF2	0.062	0.074	-10000	0	-0.15	13	13
SMAD3/SMAD4/ATF3	0.058	0.068	-10000	0	-0.14	7	7
SAP30	0.038	0.011	-10000	0	0	46	46
Cbp/p300/PIAS3	0.057	0.058	0.17	1	-0.14	27	28
JUN	0.001	0.087	0.18	9	-0.22	38	47
SMAD3/SMAD4/IRF7	0.07	0.07	-10000	0	-0.15	7	7
TFE3	0.038	0.033	0.11	1	-0.082	34	35
COL1A2	-0.093	0.25	-10000	0	-0.61	103	103
mesenchymal cell differentiation	-0.062	0.069	0.14	9	-10000	0	9
DLX1	0.04	0.008	-10000	0	0	19	19
TCF3	0.036	0.014	-10000	0	0	74	74
FOS	0.025	0.029	-10000	0	-0.05	28	28
SMAD3/SMAD4/Max	0.062	0.068	-10000	0	-0.14	6	6
Cbp/p300/SNIP1	0.058	0.055	-10000	0	-0.14	24	24
ZBTB17	0.038	0.01	0.1	3	-0.04	4	7
LAMC1	0.01	0.075	-10000	0	-0.26	26	26
TGIF2/HDAC complex/SMAD3/SMAD4	0.059	0.075	-10000	0	-0.16	13	13
IRF7	0.04	0.012	0.087	1	-10000	0	1
ESR1	0.046	0.037	0.12	90	0	91	181
HNF4A	0.038	0.01	-10000	0	0	38	38
MEF2C	0.049	0.11	0.2	145	-0.23	14	159
SMAD2-3/SMAD4	0.07	0.073	-10000	0	-0.14	6	6
Cbp/p300/Src-1	0.058	0.06	-10000	0	-0.14	31	31
IGHV3OR16-13	0.01	0.057	-10000	0	-0.45	8	8
TGIF2/HDAC complex	0.037	0.012	-10000	0	0	50	50
CREBBP	0.037	0.014	-10000	0	-0.045	2	2
SKIL	0.025	0.02	-10000	0	0	215	215
HDAC1	0.037	0.012	-10000	0	0	49	49
HDAC2	0.038	0.01	-10000	0	0	38	38
SNIP1	0.039	0.009	-10000	0	0	28	28
GCN5L2	0.039	0.012	-10000	0	-0.045	3	3
SMAD3/SMAD4/TFE3	0.076	0.083	-10000	0	-0.16	21	21
MSG1/HSC70	0.052	0.026	-10000	0	-0.13	5	5
SMAD2	0.039	0.024	-10000	0	-0.065	20	20
SMAD3	0.034	0.047	-10000	0	-0.1	13	13
SMAD3/E2F4-5/DP1/p107/SMAD4	0.019	0.065	0.16	1	-0.2	19	20
SMAD2/SMAD2/SMAD4	-0.003	0.056	0.16	9	-0.17	32	41
NCOR1	0.037	0.013	-10000	0	0	58	58
NCOA2	0.037	0.013	-10000	0	0	60	60
NCOA1	0.04	0.008	-10000	0	0	22	22
MYOD/E2A	0.051	0.024	-10000	0	-0.13	1	1
SMAD2-3/SMAD4/SP1/MIZ-1	0.084	0.12	-10000	0	-0.2	9	9
IFNB1	0.013	0.049	0.17	1	-0.16	2	3
SMAD3/SMAD4/MEF2C	0.088	0.11	0.27	47	-0.22	13	60
CITED1	0.039	0.01	-10000	0	0	35	35
SMAD2-3/SMAD4/ARC105	0.068	0.066	-10000	0	-0.13	4	4
RBL1	0.037	0.012	-10000	0	0	54	54
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.025	0.072	-10000	0	-0.41	7	7
RUNX1-3/PEBPB2	0.065	0.041	-10000	0	-0.11	13	13
SMAD7	-0.001	0.14	-10000	0	-0.36	29	29
MYC/MIZ-1	0.019	0.058	0.2	3	-0.14	49	52
SMAD3/SMAD4	-0.002	0.1	0.26	2	-0.34	22	24
IL10	0.022	0.061	0.23	15	-10000	0	15
PIASy/HDAC complex	0.036	0.014	-10000	0	-0.038	4	4
PIAS3	0.038	0.013	-10000	0	-0.002	50	50
CDK2	0.037	0.014	-10000	0	-0.042	3	3
IL5	0.023	0.061	0.23	13	-10000	0	13
CDK4	0.038	0.013	-10000	0	-0.045	3	3
PIAS4	0.036	0.014	-10000	0	-0.038	4	4
ATF3	0.036	0.013	-10000	0	0	63	63
SMAD3/SMAD4/SP1	0.054	0.11	-10000	0	-0.18	21	21
FOXG1	-0.001	0.001	-10000	0	-10000	0	0
FOXO3	0.01	0.012	-10000	0	-0.11	5	5
FOXO1	0.01	0.012	-10000	0	-0.11	5	5
FOXO4	0.01	0.012	-10000	0	-0.11	5	5
heart looping	0.049	0.1	0.2	145	-0.22	14	159
CEBPB	0.036	0.017	-10000	0	-0.061	5	5
SMAD3/SMAD4/DLX1	0.067	0.067	-10000	0	-0.14	6	6
MYOD1	0.04	0.007	-10000	0	0	16	16
SMAD3/SMAD4/HNF4	0.064	0.068	-10000	0	-0.14	6	6
SMAD3/SMAD4/GATA3	0.077	0.07	-10000	0	-0.16	1	1
SnoN/SIN3/HDAC complex/NCoR1	0.025	0.02	-10000	0	0	215	215
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.088	0.082	-10000	0	-0.14	1	1
SMAD3/SMAD4/SP1-3	0.07	0.12	-10000	0	-0.21	21	21
MED15	0	0	-10000	0	-10000	0	0
SP1	0.018	0.066	-10000	0	-0.099	122	122
SIN3B	0.036	0.014	-10000	0	0	67	67
SIN3A	0.039	0.009	-10000	0	0	30	30
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.071	0.077	-10000	0	-0.17	11	11
ITGB5	-0.004	0.091	0.21	13	-0.27	29	42
TGIF/SIN3/HDAC complex/CtBP	0.008	0.087	-10000	0	-0.26	30	30
SMAD3/SMAD4/AR	0.04	0.088	-10000	0	-0.16	30	30
AR	0.032	0.017	-10000	0	0	118	118
negative regulation of cell growth	0.019	0.076	0.19	1	-0.25	21	22
SMAD3/SMAD4/MYOD	0.068	0.067	-10000	0	-0.14	6	6
E2F5	0.036	0.013	-10000	0	0	64	64
E2F4	0.036	0.013	-10000	0	0	64	64
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.069	0.079	-10000	0	-0.15	5	5
SMAD2-3/SMAD4/FOXO1-3a-4	0.026	0.051	-10000	0	-0.29	7	7
TFDP1	0.037	0.012	-10000	0	0	55	55
SMAD3/SMAD4/AP1	0.031	0.11	0.26	3	-0.23	37	40
SMAD3/SMAD4/RUNX2	0.063	0.07	-10000	0	-0.14	9	9
TGIF2	0.037	0.012	-10000	0	0	50	50
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	0.039	0.009	-10000	0	0	30	30

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.037	0.042	-10000	0	-0.11	33	33
EFNA5	0.034	0.015	-10000	0	0	93	93
FYN	-0.015	0.033	0.18	4	-10000	0	4
neuron projection morphogenesis	0.037	0.042	-10000	0	-0.11	33	33
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.038	0.042	-10000	0	-0.11	33	33
EPHA5	0.039	0.008	-10000	0	0	24	24

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.037	0.012	-10000	0	0	49	49
HDAC2	0.038	0.01	-10000	0	0	38	38
GNB1/GNG2	0.068	0.042	-10000	0	-0.12	16	16
forebrain development	0.011	0.11	-10000	0	-0.38	29	29
GNAO1	0.035	0.015	-10000	0	0	85	85
SMO/beta Arrestin2	0.054	0.025	-10000	0	-0.13	4	4
SMO	0.04	0.009	-10000	0	-0.001	24	24
ARRB2	0.038	0.012	-10000	0	0	46	46
GLI3/SPOP	0.025	0.12	0.23	1	-0.34	29	30
mol:GTP	0	0.001	-10000	0	-10000	0	0
GSK3B	0.039	0.008	-10000	0	0	23	23
GNAI2	0.04	0.006	-10000	0	0	13	13
SIN3/HDAC complex	0.076	0.053	-10000	0	-0.11	12	12
GNAI1	0.034	0.016	-10000	0	0	93	93
XPO1	0.039	0.012	-10000	0	-0.003	38	38
GLI1/Su(fu)	0.017	0.11	-10000	0	-0.4	24	24
SAP30	0.038	0.011	-10000	0	0	46	46
mol:GDP	0.04	0.009	-10000	0	-0.001	24	24
MIM/GLI2A	0.032	0.025	-10000	0	-0.12	2	2
IFT88	0.037	0.013	-10000	0	0	61	61
GNAI3	0.038	0.011	-10000	0	0	45	45
GLI2	0.015	0.077	0.18	5	-0.26	17	22
GLI3	0.007	0.12	0.21	3	-0.35	29	32
CSNK1D	0.039	0.008	-10000	0	0	24	24
CSNK1E	0.037	0.012	-10000	0	0	53	53
SAP18	0.039	0.008	-10000	0	0	24	24
embryonic digit morphogenesis	0.037	0.013	-10000	0	0	61	61
GNG2	0.039	0.009	-10000	0	0	29	29
Gi family/GTP	0.002	0.077	-10000	0	-0.25	28	28
SIN3B	0.036	0.014	-10000	0	0	67	67
SIN3A	0.039	0.009	-10000	0	0	30	30
GLI3/Su(fu)	0.019	0.12	0.21	3	-0.33	32	35
GLI2/Su(fu)	0.022	0.086	0.18	2	-0.26	23	25
FOXA2	0.022	0.1	-10000	0	-0.57	13	13
neural tube patterning	0.011	0.11	-10000	0	-0.38	29	29
SPOP	0.04	0.008	-10000	0	0	21	21
Su(fu)/PIAS1	0.041	0.055	-10000	0	-0.19	20	20
GNB1	0.039	0.01	-10000	0	0	33	33
CSNK1G2	0.036	0.013	-10000	0	0	64	64
CSNK1G3	0.039	0.01	-10000	0	0	31	31
MTSS1	0.032	0.025	-10000	0	-0.12	2	2
embryonic limb morphogenesis	0.011	0.11	-10000	0	-0.38	29	29
SUFU	0.022	0.039	-10000	0	-0.24	10	10
LGALS3	0.036	0.014	-10000	0	0	67	67
catabolic process	0.027	0.13	-10000	0	-0.36	31	31
GLI3A/CBP	0.046	0.015	-10000	0	-10000	0	0
KIF3A	0.038	0.011	-10000	0	0	46	46
GLI1	0.01	0.11	-10000	0	-0.38	29	29
RAB23	0.04	0.006	-10000	0	0	13	13
CSNK1A1	0.039	0.008	-10000	0	0	23	23
IFT172	0.039	0.009	-10000	0	0	28	28
RBBP7	0.039	0.009	-10000	0	0	25	25
Su(fu)/Galectin3	0.037	0.053	-10000	0	-0.18	19	19
GNAZ	0.038	0.012	-10000	0	0	46	46
RBBP4	0.038	0.011	-10000	0	0	40	40
CSNK1G1	0.04	0.007	-10000	0	0	16	16
PIAS1	0.039	0.008	-10000	0	0	24	24
PRKACA	0.035	0.015	-10000	0	0	84	84
GLI2/SPOP	0.032	0.086	-10000	0	-0.27	20	20
STK36	0.039	0.011	-10000	0	-0.003	33	33
Gi family/GNB1/GNG2/GDP	-0.002	0.087	-10000	0	-0.24	38	38
PTCH1	0.011	0.1	-10000	0	-0.35	29	29
MIM/GLI1	0.024	0.1	-10000	0	-0.35	21	21
CREBBP	0.046	0.015	-10000	0	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.004	0.11	0.17	4	-0.32	34	38

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.016	0.009	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.062	0.06	0.18	72	-0.11	16	88
CDKN1B	0.013	0.091	0.21	31	-0.33	24	55
CDKN1A	0.004	0.084	0.2	9	-0.32	28	37
FRAP1	0.039	0.009	-10000	0	0	28	28
PRKDC	0.038	0.011	-10000	0	0	44	44
FOXO3	0.005	0.081	-10000	0	-0.31	30	30
AKT1	0.006	0.081	-10000	0	-0.34	26	26
BAD	0.041	0.005	-10000	0	0	7	7
AKT3	0.004	0.046	-10000	0	-0.2	26	26
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.005	0.081	-10000	0	-0.31	30	30
AKT1/ASK1	0.026	0.09	-10000	0	-0.31	31	31
BAD/YWHAZ	0.056	0.042	-10000	0	-0.11	6	6
RICTOR	0.037	0.013	-10000	0	0	59	59
RAF1	0.04	0.008	-10000	0	0	22	22
JNK cascade	-0.025	0.087	0.3	31	-10000	0	31
TSC1	0.002	0.078	0.26	1	-0.32	25	26
YWHAZ	0.034	0.016	-10000	0	0	96	96
AKT1/RAF1	0.032	0.093	0.24	1	-0.32	29	30
EP300	0.036	0.014	-10000	0	0	69	69
mol:GDP	0.004	0.083	-10000	0	-0.32	30	30
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0	0.082	0.26	1	-0.32	30	31
YWHAQ	0.04	0.007	-10000	0	0	18	18
TBC1D4	0.004	0.03	0.24	4	-0.17	7	11
MAP3K5	0.037	0.013	-10000	0	0	60	60
MAPKAP1	0.04	0.008	-10000	0	0	21	21
negative regulation of cell cycle	-0.022	0.087	0.3	17	-0.22	2	19
YWHAH	0.038	0.011	-10000	0	0	46	46
AKT1S1	0.002	0.077	0.27	1	-0.33	24	25
CASP9	0	0.079	-10000	0	-0.32	27	27
YWHAB	0.038	0.011	-10000	0	0	45	45
p27Kip1/KPNA1	0.033	0.11	0.29	6	-0.32	28	34
GBL	0.039	0.009	-10000	0	0	26	26
PDK1/Src/Hsp90	0.049	0.023	-10000	0	-0.11	6	6
YWHAE	0.037	0.013	-10000	0	0	58	58
SRC	0.039	0.009	-10000	0	0	28	28
AKT2/p21CIP1	0.007	0.077	0.2	8	-0.29	26	34
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.018	0.097	-10000	0	-0.36	27	27
CHUK	-0.002	0.084	-10000	0	-0.32	30	30
BAD/BCL-XL	0.025	0.086	0.23	1	-0.31	26	27
mTORC2	0.077	0.061	-10000	0	-0.11	32	32
AKT2	0.014	0.025	-10000	0	-0.2	7	7
FOXO1-3a-4/14-3-3 family	0.024	0.11	0.24	3	-0.35	20	23
PDPK1	0.039	0.009	-10000	0	0	29	29
MDM2	0.005	0.088	0.2	15	-0.32	28	43
MAPKKK cascade	-0.032	0.092	0.32	29	-0.24	1	30
MDM2/Cbp/p300	0.04	0.1	0.33	3	-0.32	28	31
TSC1/TSC2	-0.003	0.083	0.28	5	-0.31	30	35
proteasomal ubiquitin-dependent protein catabolic process	0.038	0.1	0.32	3	-0.31	28	31
glucose import	-0.004	0.036	0.21	11	-0.16	7	18
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.014	0.089	0.25	1	-0.34	11	12
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.005	0.033	0.21	8	-0.16	7	15
GSK3A	0.005	0.084	0.22	11	-0.32	26	37
FOXO1	0.005	0.081	-10000	0	-0.31	30	30
GSK3B	0.004	0.087	0.22	13	-0.32	28	41
SFN	0.035	0.015	-10000	0	0	83	83
G1/S transition of mitotic cell cycle	0.008	0.097	0.28	11	-0.32	27	38
p27Kip1/14-3-3 family	0.02	0.08	0.22	1	-0.35	11	12
PRKACA	0.035	0.015	-10000	0	0	84	84
KPNA1	0.039	0.009	-10000	0	0	28	28
HSP90AA1	0	0	-10000	0	-10000	0	0
YWHAG	0.039	0.009	-10000	0	0	25	25
RHEB	0.037	0.012	-10000	0	0	53	53
CREBBP	0.037	0.012	-10000	0	0	53	53

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.037	0.013	-10000	0	0	58	58
NFATC1	0.014	0.1	0.26	5	-0.34	16	21
NFATC2	0.023	0.061	0.16	12	-0.19	15	27
NFATC3	0.025	0.016	-10000	0	-10000	0	0
YWHAE	0.037	0.013	-10000	0	0	58	58
Calcineurin A alpha-beta B1/CABIN1	-0.007	0.087	0.17	2	-0.25	32	34
Exportin 1/Ran/NUP214	0.064	0.051	-10000	0	-0.11	32	32
mol:DAG	0.001	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.026	0.1	-10000	0	-0.26	23	23
BCL2/BAX	0.051	0.023	-10000	0	-0.13	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	0.029	0.019	-10000	0	-0.12	5	5
CaM/Ca2+	0.029	0.019	-10000	0	-0.12	5	5
BAX	0.039	0.008	-10000	0	0	23	23
MAPK14	0.04	0.008	-10000	0	0	20	20
BAD	0.041	0.005	-10000	0	0	7	7
CABIN1/MEF2D	0.011	0.093	-10000	0	-0.25	29	29
Calcineurin A alpha-beta B1/BCL2	0.036	0.014	-10000	0	0	67	67
FKBP8	0.036	0.014	-10000	0	0	71	71
activation-induced cell death of T cells	-0.011	0.092	0.25	29	-10000	0	29
KPNB1	0.039	0.009	-10000	0	0	25	25
KPNA2	0.035	0.014	-10000	0	0	79	79
XPO1	0.039	0.01	-10000	0	0	35	35
SFN	0.035	0.015	-10000	0	0	83	83
MAP3K8	0.04	0.009	-10000	0	0	24	24
NFAT4/CK1 alpha	0.027	0.044	0.18	1	-0.15	10	11
MEF2D/NFAT1/Cbp/p300	0.067	0.093	0.24	3	-0.2	14	17
CABIN1	-0.006	0.087	0.17	2	-0.25	32	34
CALM1	0.04	0.009	-10000	0	0	26	26
RAN	0.04	0.008	-10000	0	0	21	21
MAP3K1	0.036	0.013	-10000	0	0	63	63
CAMK4	0.037	0.012	-10000	0	0	55	55
mol:Ca2+	0.001	0.004	-10000	0	-10000	0	0
MAPK3	0.04	0.007	-10000	0	0	18	18
YWHAH	0.038	0.011	-10000	0	0	46	46
Calcineurin A alpha-beta B1/AKAP79/PKA	0.05	0.026	-10000	0	-0.13	2	2
YWHAB	0.038	0.011	-10000	0	0	45	45
MAPK8	0.04	0.01	-10000	0	0	29	29
MAPK9	0.038	0.011	-10000	0	0	39	39
YWHAG	0.039	0.009	-10000	0	0	25	25
FKBP1A	0.038	0.011	-10000	0	0	44	44
NFAT1-c-4/YWHAQ	0.028	0.11	0.26	4	-0.29	25	29
PRKCH	0.038	0.01	-10000	0	0	36	36
CABIN1/Cbp/p300	0.043	0.051	-10000	0	-0.16	24	24
CASP3	0.037	0.013	-10000	0	0	62	62
PIM1	0.038	0.01	-10000	0	0	36	36
Calcineurin A alpha-beta B1/FKBP12/FK506	0.026	0.011	-10000	0	-0.1	2	2
apoptosis	0.017	0.035	-10000	0	-0.19	10	10
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.023	0.075	-10000	0	-0.28	15	15
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.039	0.009	-10000	0	0	28	28
JNK2/NFAT4	0.027	0.066	-10000	0	-0.15	61	61
BAD/BCL-XL	0.051	0.031	-10000	0	-0.13	10	10
PRKCD	0.037	0.012	-10000	0	0	51	51
NUP214	0.038	0.011	-10000	0	0	43	43
PRKCZ	0.04	0.009	-10000	0	0	27	27
PRKCA	0.035	0.015	-10000	0	0	86	86
PRKCG	0.039	0.009	-10000	0	0	27	27
PRKCQ	0.035	0.015	-10000	0	0	85	85
FKBP38/BCL2	0.046	0.028	-10000	0	-0.13	2	2
EP300	0.037	0.014	-10000	0	0	69	69
PRKCB1	0.038	0.011	-10000	0	0	46	46
CSNK2A1	0.038	0.012	-10000	0	0	47	47
NFATc/JNK1	0.028	0.11	0.26	4	-0.32	17	21
CaM/Ca2+/FKBP38	0.047	0.027	-10000	0	-0.13	4	4
FKBP12/FK506	0.028	0.012	-10000	0	-0.12	2	2
CSNK1A1	0.017	0.018	0.097	5	-0.11	4	9
CaM/Ca2+/CAMK IV	0.048	0.027	-10000	0	-0.11	7	7
NFATc/ERK1	0.029	0.11	0.28	5	-0.32	16	21
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.023	0.1	-10000	0	-0.24	27	27
NR4A1	0.012	0.074	0.2	15	-0.22	22	37
GSK3B	0.04	0.009	-10000	0	0	23	23
positive T cell selection	0.025	0.015	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.021	0.049	0.12	9	-0.19	12	21
RCH1/ KPNB1	0.036	0.062	-10000	0	-0.14	58	58
YWHAQ	0.04	0.007	-10000	0	0	18	18
PRKACA	0.035	0.015	-10000	0	0	84	84
AKAP5	0.04	0.007	-10000	0	0	14	14
MEF2D	0.041	0.008	-10000	0	0	18	18
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.034	0.016	-10000	0	0	96	96
NFATc/p38 alpha	0.03	0.11	0.28	5	-0.31	17	22
CREBBP	0.038	0.013	-10000	0	0	53	53
BCL2	0.036	0.014	-10000	0	0	67	67

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.053	0.094	-10000	0	-0.2	39	39
Ran/GTP/Exportin 1/HDAC1	-0.029	0.032	-10000	0	-0.12	45	45
NF kappa B1 p50/RelA/I kappa B alpha	0.022	0.1	0.24	1	-0.28	35	36
SUMO1	0.04	0.007	-10000	0	0	14	14
ZFPM1	0.035	0.015	-10000	0	0	86	86
NPC/RanGAP1/SUMO1/Ubc9	0.009	0.034	-10000	0	-0.14	25	25
FKBP3	0.039	0.009	-10000	0	0	30	30
Histones	0.069	0.085	0.24	1	-0.24	13	14
YY1/LSF	0.01	0.084	-10000	0	-0.23	42	42
SMG5	0	0	-10000	0	-10000	0	0
RAN	0.04	0.008	-10000	0	0	21	21
I kappa B alpha/HDAC3	0.016	0.059	-10000	0	-0.18	38	38
I kappa B alpha/HDAC1	0.029	0.088	0.21	1	-0.23	44	45
SAP18	0.039	0.008	-10000	0	0	24	24
RELA	0.015	0.083	0.23	2	-0.25	24	26
HDAC1/Smad7	0.063	0.051	-10000	0	-0.12	31	31
RANGAP1	0.037	0.012	-10000	0	0	54	54
HDAC3/TR2	0.045	0.061	0.21	1	-0.23	14	15
NuRD/MBD3 Complex	0.008	0.094	-10000	0	-0.29	30	30
NF kappa B1 p50/RelA	0.019	0.1	0.22	2	-0.27	38	40
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.039	0.01	-10000	0	0	31	31
GATA1	0.041	0.002	-10000	0	0	1	1
Mad/Max	0.058	0.013	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.002	0.1	-10000	0	-0.27	43	43
RBBP7	0.039	0.009	-10000	0	0	25	25
NPC	0.019	0.022	-10000	0	-0.083	23	23
RBBP4	0.038	0.011	-10000	0	0	40	40
MAX	0.04	0.006	-10000	0	0	12	12
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.04	0.008	-10000	0	0	22	22
NFKBIA	0.01	0.066	-10000	0	-0.26	28	28
KAT2B	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.009	0.084	-10000	0	-0.27	26	26
SIN3 complex	0.076	0.053	-10000	0	-0.11	12	12
SMURF1	0.04	0.006	-10000	0	0	13	13
CHD3	0.037	0.013	-10000	0	0	56	56
SAP30	0.038	0.011	-10000	0	0	46	46
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.037	0.013	-10000	0	0	58	58
YY1/HDAC3	0.015	0.077	-10000	0	-0.24	27	27
YY1/HDAC2	0.013	0.078	-10000	0	-0.22	39	39
YY1/HDAC1	0.01	0.08	-10000	0	-0.22	39	39
NuRD/MBD2 Complex (MeCP1)	0.01	0.095	-10000	0	-0.29	30	30
PPARG	0.027	0.066	0.25	2	-0.2	26	28
HDAC8/hEST1B	0.041	0.035	-10000	0	-0.11	20	20
UBE2I	0.039	0.009	-10000	0	0	27	27
beta TrCP1/SCF ubiquitin ligase complex	0.039	0.008	-10000	0	0	22	22
TNFRSF1A	0.036	0.014	-10000	0	0	72	72
HDAC3/SMRT (N-CoR2)	0.046	0.06	0.21	1	-0.22	13	14
MBD3L2	0.038	0.011	-10000	0	0	43	43
ubiquitin-dependent protein catabolic process	0.063	0.051	-10000	0	-0.12	31	31
CREBBP	0.037	0.012	-10000	0	0	53	53
NuRD/MBD3/MBD3L2 Complex	0.004	0.11	0.18	8	-0.27	46	54
HDAC1	0.038	0.012	-10000	0	0	49	49
HDAC3	0.023	0.031	-10000	0	-0.24	4	4
HDAC2	0.038	0.01	-10000	0	0	38	38
YY1	0.005	0.056	-10000	0	-0.24	23	23
HDAC8	0.039	0.009	-10000	0	0	26	26
SMAD7	0.038	0.01	-10000	0	0	36	36
NCOR2	0.039	0.01	-10000	0	0	31	31
MXD1	0.04	0.007	-10000	0	0	15	15
STAT3	0.008	0.067	-10000	0	-0.24	33	33
NFKB1	0.036	0.013	-10000	0	0	66	66
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.039	0.009	-10000	0	0	30	30
YY1/LSF/HDAC1	0.021	0.093	-10000	0	-0.22	46	46
YY1/SAP30/HDAC1	0.024	0.086	-10000	0	-0.2	40	40
EP300	0.036	0.014	-10000	0	0	69	69
STAT3 (dimer non-phopshorylated)	0.008	0.066	-10000	0	-0.24	33	33
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.066	-10000	0	-0.26	28	28
histone deacetylation	0.011	0.095	0.17	5	-0.29	30	35
STAT3 (dimer non-phopshorylated)/HDAC3	0.018	0.083	-10000	0	-0.28	22	22
nuclear export	-0.041	0.035	0.11	20	-10000	0	20
PRKACA	0.035	0.015	-10000	0	0	84	84
GATAD2B	0.038	0.011	-10000	0	0	41	41
GATAD2A	0.037	0.012	-10000	0	0	54	54
GATA2/HDAC3	0.046	0.059	0.21	1	-0.21	15	16
GATA1/HDAC1	0.05	0.041	-10000	0	-0.13	24	24
GATA1/HDAC3	0.049	0.06	0.21	1	-0.21	17	18
CHD4	0.036	0.014	-10000	0	0	69	69
TNF-alpha/TNFR1A	0.047	0.038	-10000	0	-0.13	16	16
SIN3/HDAC complex/Mad/Max	0.015	0.08	-10000	0	-0.26	23	23
NuRD Complex	0.001	0.11	0.18	7	-0.28	40	47
positive regulation of chromatin silencing	0.065	0.082	0.23	1	-0.24	13	14
SIN3B	0.036	0.014	-10000	0	0	67	67
MTA2	0.04	0.006	-10000	0	0	10	10
SIN3A	0.039	0.009	-10000	0	0	30	30
XPO1	0.039	0.01	-10000	0	0	35	35
SUMO1/HDAC1	0.034	0.066	-10000	0	-0.18	25	25
HDAC complex	0.073	0.074	-10000	0	-0.13	51	51
GATA1/Fog1	0.051	0.022	-10000	0	-10000	0	0
FKBP25/HDAC1/HDAC2	0.058	0.06	-10000	0	-0.13	41	41
TNF	0.04	0.008	-10000	0	0	22	22
negative regulation of cell growth	0.015	0.081	0.17	1	-0.26	24	25
NuRD/MBD2/PRMT5 Complex	0.01	0.095	-10000	0	-0.29	30	30
Ran/GTP/Exportin 1	0.035	0.071	-10000	0	-0.18	36	36
NF kappa B/RelA/I kappa B alpha	0.005	0.078	-10000	0	-0.26	31	31
SIN3/HDAC complex/NCoR1	0.001	0.093	-10000	0	-0.24	44	44
TFCP2	0.039	0.01	-10000	0	0	35	35
NR2C1	0.039	0.01	-10000	0	0	33	33
MBD3	0.036	0.014	-10000	0	0	69	69
MBD2	0.039	0.01	-10000	0	0	32	32

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.038	0.011	-10000	0	0	43	43
SMAD2	0.012	0.052	0.19	7	-0.23	3	10
SMAD3	0.014	0.054	0.28	1	-0.3	4	5
SMAD3/SMAD4	-0.015	0.16	-10000	0	-0.39	78	78
SMAD4/Ubc9/PIASy	0.065	0.041	-10000	0	-0.13	9	9
SMAD2/SMAD2/SMAD4	0.053	0.083	0.27	1	-0.18	9	10
PPM1A	0.04	0.006	-10000	0	0	10	10
CALM1	0.039	0.009	-10000	0	0	26	26
SMAD2/SMAD4	0.03	0.051	0.22	2	-0.18	7	9
MAP3K1	0.036	0.013	-10000	0	0	63	63
TRAP-1/SMAD4	0.049	0.041	-10000	0	-0.14	21	21
MAPK3	0.04	0.007	-10000	0	0	18	18
MAPK1	0.038	0.011	-10000	0	0	44	44
NUP214	0.038	0.011	-10000	0	0	43	43
CTDSP1	0.04	0.007	-10000	0	0	15	15
CTDSP2	0.039	0.009	-10000	0	0	29	29
CTDSPL	0.04	0.007	-10000	0	0	15	15
KPNB1	0.039	0.009	-10000	0	0	25	25
TGFBRAP1	0.04	0.008	-10000	0	0	20	20
UBE2I	0.039	0.009	-10000	0	0	27	27
NUP153	0.037	0.013	-10000	0	0	57	57
KPNA2	0.035	0.014	-10000	0	0	79	79
PIAS4	0.037	0.012	-10000	0	0	54	54

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.053	0.025	-10000	0	-0.13	4	4
FBXW11	0.04	0.008	-10000	0	0	22	22
NF kappa B1 p50/c-Rel	0.028	0.036	-10000	0	-0.12	26	26
NF kappa B1 p50/RelA/I kappa B alpha	0.019	0.077	0.26	1	-0.22	21	22
NFKBIA	0.003	0.06	-10000	0	-0.15	53	53
MAPK14	0.04	0.008	-10000	0	0	20	20
NF kappa B1 p105/p50	0.027	0.039	-10000	0	-0.13	27	27
ARRB2	0.014	0.028	-10000	0	-0.2	9	9
REL	0.04	0.007	-10000	0	0	15	15
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.027	0.035	-10000	0	-0.12	23	23
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.028	0.038	-10000	0	-0.12	29	29
PIK3CA	0.029	0.019	-10000	0	0	166	166
NF kappa B1 p50 dimer	0.019	0.039	-10000	0	-0.14	28	28
PIK3R1	0.034	0.016	-10000	0	0	99	99
NFKB1	-0.017	0.008	-10000	0	-10000	0	0
RELA	0.04	0.006	-10000	0	0	10	10
positive regulation of anti-apoptosis	0.012	0.051	0.14	1	-0.18	12	13
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.018	0.081	0.23	1	-0.22	24	25
SRC	0.039	0.009	-10000	0	0	28	28
PI3K	0.023	0.06	-10000	0	-0.15	44	44
NF kappa B1 p50/RelA	0.012	0.051	0.14	1	-0.18	12	13
IKBKB	0.038	0.011	-10000	0	0	41	41
beta TrCP1/SCF ubiquitin ligase complex	0.039	0.008	-10000	0	0	22	22
SYK	0.036	0.014	-10000	0	0	67	67
I kappa B alpha/PIK3R1	0.016	0.068	0.27	1	-0.24	12	13
cell death	0.017	0.078	0.22	1	-0.22	24	25
NF kappa B1 p105/c-Rel	0.028	0.036	-10000	0	-0.12	26	26
LCK	0.039	0.009	-10000	0	0	25	25
BCL3	0.037	0.012	-10000	0	0	51	51

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.02	0.076	-10000	0	-0.39	10	10
SMARCC2	0.039	0.009	-10000	0	0	29	29
SMARCC1	0.04	0.007	-10000	0	0	18	18
TBX21	0.04	0.06	0.41	2	-0.26	1	3
SUMO2	0.037	0.015	-10000	0	-0.014	36	36
STAT1 (dimer)	0.022	0.064	-10000	0	-0.18	45	45
FKBP4	0.036	0.014	-10000	0	0	73	73
FKBP5	0.03	0.018	-10000	0	0	142	142
GR alpha/HSP90/FKBP51/HSP90	-0.034	0.074	0.21	3	-0.21	17	20
PRL	0.044	0.063	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	-0.056	0.12	0.4	4	-0.34	2	6
RELA	0.012	0.095	-10000	0	-0.16	117	117
FGG	-0.053	0.11	0.35	4	-0.32	1	5
GR beta/TIF2	-0.032	0.08	0.25	2	-0.24	6	8
IFNG	0.045	0.1	-10000	0	-0.41	1	1
apoptosis	-0.053	0.17	-10000	0	-0.41	75	75
CREB1	0.048	0.009	-10000	0	-10000	0	0
histone acetylation	0.023	0.079	0.33	6	-0.39	6	12
BGLAP	0.045	0.083	-10000	0	-0.88	2	2
GR/PKAc	0.031	0.083	0.3	1	-0.15	22	23
NF kappa B1 p50/RelA	0.011	0.17	-10000	0	-0.29	115	115
SMARCD1	0.04	0.007	-10000	0	0	17	17
MDM2	-0.013	0.047	0.13	7	-0.24	8	15
GATA3	0.049	0.013	-10000	0	-10000	0	0
AKT1	0.035	0.015	0.17	2	-0.048	6	8
CSF2	0.012	0.052	-10000	0	-10000	0	0
GSK3B	0.037	0.014	-10000	0	-0.012	38	38
NR1I3	-0.045	0.15	-10000	0	-0.41	29	29
CSN2	-0.049	0.096	0.28	6	-0.3	2	8
BRG1/BAF155/BAF170/BAF60A	0.074	0.065	-10000	0	-0.13	30	30
NFATC1	0.043	0.017	-10000	0	-10000	0	0
POU2F1	0.045	0.008	-10000	0	-10000	0	0
CDKN1A	-0.043	0.12	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.001	0.004	-10000	0	-10000	0	0
SFN	0.035	0.015	-10000	0	0	83	83
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.03	0.079	0.23	2	-0.2	24	26
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.1	0.28	-10000	0	-0.7	89	89
JUN	0.04	0.096	0.33	8	-0.28	4	12
IL4	0.042	0.057	-10000	0	-10000	0	0
CDK5R1	0.038	0.011	-10000	0	0	40	40
PRKACA	0.035	0.015	-10000	0	0	84	84
cortisol/GR alpha (monomer)/AP-1	-0.039	0.067	0.2	11	-0.22	23	34
GR alpha/HSP90/FKBP51/HSP90/PP5C	-0.024	0.079	0.24	2	-0.2	17	19
cortisol/GR alpha (monomer)	-0.069	0.13	0.42	5	-0.4	1	6
NCOA2	0.037	0.013	-10000	0	0	60	60
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	0.032	0.055	-10000	0	-0.13	29	29
AP-1/NFAT1-c-4	0.038	0.14	-10000	0	-0.38	18	18
AFP	0.03	0.094	-10000	0	-10000	0	0
SUV420H1	0.039	0.009	-10000	0	0	30	30
IRF1	-0.1	0.22	-10000	0	-0.57	82	82
TP53	0.035	0.028	-10000	0	-10000	0	0
PPP5C	0.039	0.009	-10000	0	0	27	27
KRT17	0.028	0.16	-10000	0	-0.77	11	11
KRT14	0.023	0.19	0.5	8	-1.1	12	20
TBP	0.043	0.027	-10000	0	-0.32	2	2
CREBBP	0.03	0.054	0.33	13	-10000	0	13
HDAC1	0.033	0.012	-10000	0	-0.058	2	2
HDAC2	0.037	0.01	-10000	0	-10000	0	0
AP-1	0.038	0.14	-10000	0	-0.38	18	18
MAPK14	0.037	0.015	-10000	0	-0.015	39	39
MAPK10	0.033	0.02	-10000	0	-0.009	90	90
MAPK11	0.027	0.021	-10000	0	-0.002	170	170
KRT5	-0.01	0.26	-10000	0	-0.83	43	43
interleukin-1 receptor activity	-0.001	0	-10000	0	-10000	0	0
NCOA1	0.04	0.011	-10000	0	-0.068	2	2
STAT1	0.022	0.064	-10000	0	-0.18	45	45
CGA	0.045	0.065	0.3	1	-10000	0	1
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.059	0.11	0.3	4	-0.34	37	41
MAPK3	0.035	0.019	-10000	0	-0.019	52	52
MAPK1	0.035	0.017	-10000	0	-0.01	65	65
ICAM1	-0.079	0.32	-10000	0	-0.77	89	89
NFKB1	0.006	0.11	-10000	0	-0.19	111	111
MAPK8	0.049	0.083	0.48	2	-0.26	3	5
MAPK9	0.035	0.017	-10000	0	-0.01	59	59
cortisol/GR alpha (dimer)	-0.056	0.18	-10000	0	-0.42	79	79
BAX	-0.05	0.12	-10000	0	-10000	0	0
POMC	0.052	0.092	0.49	2	-10000	0	2
EP300	0.028	0.047	0.32	10	-10000	0	10
cortisol/GR alpha (dimer)/p53	-0.073	0.12	0.41	4	-0.36	1	5
proteasomal ubiquitin-dependent protein catabolic process	-0.026	0.047	0.25	5	-0.22	8	13
SGK1	-0.025	0.11	0.34	10	-0.3	47	57
IL13	0.047	0.094	-10000	0	-10000	0	0
IL6	0.011	0.16	-10000	0	-0.64	15	15
PRKACG	0.04	0.008	-10000	0	0	22	22
IL5	0.046	0.096	-10000	0	-10000	0	0
IL2	0.037	0.12	-10000	0	-0.53	6	6
CDK5	0.035	0.014	-10000	0	0	69	69
PRKACB	0.038	0.011	-10000	0	0	44	44
HSP90AA1	0	0	-10000	0	-10000	0	0
IL8	-0.013	0.22	-10000	0	-0.8	32	32
CDK5R1/CDK5	0.044	0.04	-10000	0	-0.13	19	19
NF kappa B1 p50/RelA/PKAc	0.042	0.15	-10000	0	-0.22	91	91
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.043	0.11	0.37	5	-0.31	1	6
SMARCA4	0.034	0.015	-10000	0	0	92	92
chromatin remodeling	-0.03	0.091	0.27	4	-0.36	10	14
NF kappa B1 p50/RelA/Cbp	0.025	0.16	0.41	6	-0.25	102	108
JUN (dimer)	0.04	0.096	0.33	8	-0.28	4	12
YWHAH	0.038	0.011	-10000	0	0	46	46
VIPR1	0.041	0.057	0.4	1	-0.26	1	2
NR3C1	-0.044	0.091	0.3	3	-0.32	3	6
NR4A1	0.038	0.018	-10000	0	-10000	0	0
TIF2/SUV420H1	0.042	0.051	-10000	0	-0.14	36	36
MAPKKK cascade	-0.053	0.17	-10000	0	-0.41	75	75
cortisol/GR alpha (dimer)/Src-1	-0.052	0.13	0.4	5	-0.34	1	6
PBX1	0.043	0.012	-10000	0	-10000	0	0
POU1F1	0.046	0.008	-10000	0	-10000	0	0
SELE	0.023	0.11	-10000	0	-0.4	4	4
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.03	0.091	0.27	4	-0.36	10	14
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.043	0.11	0.37	5	-0.31	1	6
mol:cortisol	-0.042	0.066	0.21	7	-10000	0	7
MMP1	0.008	0.16	-10000	0	-0.75	19	19

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.016	0.088	-10000	0	-0.38	23	23
Crk/p130 Cas/Paxillin	0.005	0.037	-10000	0	-0.18	4	4
JUN	0.002	0.062	0.19	4	-0.23	13	17
HRAS	0.039	0.01	-10000	0	0	31	31
RET51/GFRalpha1/GDNF/GRB10	0.088	0.039	-10000	0	-0.11	5	5
RAP1A	0.039	0.01	-10000	0	0	35	35
FRS2	0.038	0.011	-10000	0	0	41	41
RAP1A/GDP	0.023	0.031	-10000	0	-0.12	22	22
RET51/GFRalpha1/GDNF/DOK1	0.088	0.039	-10000	0	-0.11	5	5
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.039	0.009	-10000	0	0	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.038	0.012	-10000	0	0	49	49
RET9/GFRalpha1/GDNF/Enigma	0.064	0.033	-10000	0	-0.1	2	2
RHOA	0.04	0.006	-10000	0	0	13	13
RAP1A/GTP	0.075	0.05	-10000	0	-0.1	15	15
GRB7	0.037	0.013	-10000	0	0	57	57
RET51/GFRalpha1/GDNF	0.078	0.045	-10000	0	-0.11	3	3
MAPKKK cascade	0.032	0.046	-10000	0	-0.14	3	3
BCAR1	0.036	0.013	-10000	0	0	65	65
RET9/GFRalpha1/GDNF/IRS1	0.063	0.034	-10000	0	-0.1	5	5
lamellipodium assembly	0.03	0.05	-10000	0	-0.18	3	3
RET51/GFRalpha1/GDNF/SHC	0.088	0.036	-10000	0	-0.11	1	1
PIK3CA	0.029	0.019	-10000	0	0	166	166
RET9/GFRalpha1/GDNF/SHC	0.064	0.033	-10000	0	-0.1	2	2
RET9/GFRalpha1/GDNF/Shank3	0.05	0.039	-10000	0	-0.1	1	1
MAPK3	-0.009	0.063	0.18	38	-10000	0	38
DOK1	0.04	0.008	-10000	0	0	22	22
DOK6	0.038	0.011	-10000	0	0	45	45
PXN	0.04	0.006	-10000	0	0	10	10
neurite development	0	0.059	0.22	13	-0.2	4	17
DOK5	0.022	0.021	-10000	0	0	260	260
GFRA1	0.037	0.012	-10000	0	0	54	54
MAPK8	0.013	0.059	0.2	1	-0.23	10	11
HRAS/GTP	0.08	0.046	-10000	0	-0.15	3	3
tube development	0.047	0.043	0.24	9	-0.1	2	11
MAPK1	-0.01	0.061	0.18	34	-10000	0	34
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.02	0.046	-10000	0	-0.17	24	24
Rac1/GDP	0.029	0.009	-10000	0	-0.12	1	1
SRC	0.039	0.009	-10000	0	0	28	28
PDLIM7	0.039	0.009	-10000	0	0	30	30
RET51/GFRalpha1/GDNF/Dok6	0.093	0.052	-10000	0	-0.11	1	1
SHC1	0.039	0.008	-10000	0	0	23	23
RET51/GFRalpha1/GDNF/Dok4	0.086	0.039	-10000	0	-0.11	1	1
RET51/GFRalpha1/GDNF/Dok5	0.039	0.078	-10000	0	-0.11	88	88
PRKCA	0.035	0.015	-10000	0	0	86	86
HRAS/GDP	0.029	0.007	-10000	0	-10000	0	0
CREB1	0.036	0.06	-10000	0	-0.37	4	4
PIK3R1	0.034	0.016	-10000	0	0	99	99
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.024	0.032	-10000	0	-0.14	11	11
RET51/GFRalpha1/GDNF/Grb7	0.083	0.044	-10000	0	-0.11	6	6
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.039	0.008	-10000	0	0	23	23
DOK4	0.038	0.01	-10000	0	0	37	37
JNK cascade	0.002	0.062	0.18	6	-0.22	13	19
RET9/GFRalpha1/GDNF/FRS2	0.059	0.04	-10000	0	-0.1	11	11
SHANK3	0.03	0.018	-10000	0	0	152	152
RASA1	0.037	0.013	-10000	0	0	56	56
NCK1	0.036	0.014	-10000	0	0	70	70
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.023	0.037	-10000	0	-0.14	22	22
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.026	0.048	-10000	0	-0.17	24	24
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	0.018	0.056	-10000	0	-0.16	35	35
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.029	0.039	-10000	0	-0.15	19	19
PI3K	0.045	0.064	0.22	8	-0.25	2	10
SOS1	0.037	0.012	-10000	0	0	51	51
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.062	0.047	-10000	0	-0.1	2	2
GRB10	0.04	0.008	-10000	0	0	22	22
activation of MAPKK activity	0.029	0.052	-10000	0	-0.31	5	5
RET51/GFRalpha1/GDNF/FRS2	0.083	0.046	-10000	0	-0.11	11	11
GAB1	0.037	0.013	-10000	0	0	58	58
IRS1	0.04	0.008	-10000	0	0	22	22
IRS2	0.039	0.009	-10000	0	0	30	30
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.029	0.034	-10000	0	-0.17	1	1
RET51/GFRalpha1/GDNF/PKC alpha	0.075	0.057	-10000	0	-0.11	30	30
GRB2	0.04	0.008	-10000	0	0	21	21
PRKACA	0.035	0.015	-10000	0	0	84	84
GDNF	0.039	0.01	-10000	0	0	35	35
RAC1	0.039	0.009	-10000	0	0	28	28
RET51/GFRalpha1/GDNF/IRS1	0.088	0.038	-10000	0	-0.11	5	5
Rac1/GTP	0.044	0.063	0.2	4	-0.22	3	7
RET9/GFRalpha1/GDNF	0.047	0.021	-10000	0	-0.11	1	1
GFRalpha1/GDNF	0.051	0.024	-10000	0	-0.13	1	1

×

Sphingosine 1-phosphate (S1P) pathway

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
SPHK2	0.04	0.008	-10000	0	0	20	20
SPHK1	0.039	0.008	-10000	0	0	24	24
GNAI2	0.04	0.006	-10000	0	0	13	13
mol:S1P	0.015	0.025	-10000	0	-0.17	9	9
GNAO1	0.035	0.015	-10000	0	0	85	85
mol:Sphinganine-1-P	-0.019	0.006	-10000	0	-10000	0	0
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.05	0.048	-10000	0	-0.16	10	10
GNAI3	0.038	0.011	-10000	0	0	45	45
G12/G13	0.053	0.028	-10000	0	-0.13	8	8
S1PR3	0	0	-10000	0	-10000	0	0
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	0.04	0.006	-10000	0	0	11	11
S1P1/S1P	0.036	0.043	0.16	1	-0.12	35	36
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
GNAI1	0.034	0.015	-10000	0	0	93	93
S1P/S1P5/G12	0.031	0.039	-10000	0	-0.14	10	10
S1P/S1P3/Gq	0.016	0.074	0.17	1	-0.24	35	36
S1P/S1P4/Gi	-0.009	0.091	0.15	1	-0.2	68	69
GNAQ	0.038	0.012	-10000	0	0	48	48
GNAZ	0.038	0.011	-10000	0	0	46	46
GNA14	0.039	0.009	-10000	0	0	29	29
GNA15	0.036	0.014	-10000	0	0	68	68
GNA12	0.039	0.01	-10000	0	0	33	33
GNA13	0.039	0.008	-10000	0	0	23	23
GNA11	0.037	0.013	-10000	0	0	61	61
ABCC1	0.039	0.009	-10000	0	0	27	27

×

Insulin 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
CBL/APS/CAP	0.059	0.041	-10000	0	-0.12	10	10
TC10/GTP	0.051	0.035	-10000	0	-0.1	11	11
Insulin Receptor/Insulin/IRS1/Shp2	0.086	0.058	-10000	0	-0.12	22	22
HRAS	0.039	0.01	-10000	0	0	31	31
APS homodimer	0	0	-10000	0	-10000	0	0
GRB14	0.038	0.012	-10000	0	0	49	49
FOXO3	-0.004	0.009	0.022	12	-0.036	6	18
AKT1	0.022	0.1	0.21	56	-0.17	3	59
INSR	0.041	0.016	0.081	10	-0.049	1	11
Insulin Receptor/Insulin	0.084	0.058	0.24	37	-0.14	4	41
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.04	0.008	-10000	0	0	22	22
SORBS1	0.039	0.009	-10000	0	0	30	30
CRK	0.038	0.012	-10000	0	0	49	49
PTPN1	-0.007	0.04	0.15	28	-0.24	1	29
CAV1	-0.007	0.042	0.17	17	-10000	0	17
CBL/APS/CAP/Crk-II/C3G	0.08	0.04	-10000	0	-0.1	6	6
Insulin Receptor/Insulin/IRS1/NCK2	0.093	0.046	-10000	0	-0.1	9	9
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.037	0.063	-10000	0	-0.11	44	44
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.023	0.097	0.22	1	-0.31	36	37
RPS6KB1	0.012	0.093	0.16	126	-0.18	8	134
PARD6A	0.037	0.013	-10000	0	0	61	61
CBL	0.04	0.008	-10000	0	0	20	20
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.023	0.078	-10000	0	-0.7	6	6
PIK3R1	0.034	0.016	-10000	0	0	99	99
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.054	0.083	0.2	25	-0.18	11	36
HRAS/GTP	-0.026	0.032	0.049	2	-0.11	19	21
Insulin Receptor	0.041	0.015	0.081	10	-0.049	1	11
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.1	0.06	-10000	0	-0.11	9	9
PRKCI	-0.013	0.14	-10000	0	-0.37	61	61
Insulin Receptor/Insulin/GRB14/PDK1	0.017	0.051	-10000	0	-0.12	41	41
SHC1	0.039	0.008	-10000	0	0	23	23
negative regulation of MAPKKK cascade	0.049	0.079	-10000	0	-0.53	6	6
PI3K	0.047	0.071	-10000	0	-0.11	44	44
NCK2	0.041	0.004	-10000	0	0	6	6
RHOQ	0.039	0.009	-10000	0	0	25	25
mol:H2O2	-0.002	0.004	0.019	1	-0.032	1	2
HRAS/GDP	0.029	0.007	-10000	0	-10000	0	0
AKT2	0.018	0.094	0.2	47	-0.17	3	50
PRKCZ	0.025	0.11	-10000	0	-0.33	41	41
SH2B2	0	0	-10000	0	-10000	0	0
SHC/SHIP	-0.008	0.04	0.16	16	-0.12	1	17
F2RL2	0.036	0.013	-10000	0	0	63	63
TRIP10	0.038	0.012	-10000	0	0	49	49
Insulin Receptor/Insulin/Shc	0.07	0.037	-10000	0	-0.1	5	5
TC10/GTP/CIP4/Exocyst	0.046	0.029	-10000	0	-0.11	12	12
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.092	0.069	-10000	0	-0.12	20	20
RAPGEF1	0.039	0.009	-10000	0	0	26	26
RASA1	0.037	0.013	-10000	0	0	56	56
NCK1	0.036	0.014	-10000	0	0	70	70
CBL/APS/CAP/Crk-II	0.065	0.034	-10000	0	-0.11	6	6
TC10/GDP	0.027	0.019	-10000	0	-0.12	8	8
Insulin Receptor/Insulin/SHC/GRB10	0.089	0.051	-10000	0	-0.1	11	11
INPP5D	-0.013	0.017	0.053	11	-0.091	8	19
SOS1	0.037	0.012	-10000	0	0	51	51
SGK1	-0.004	0.004	-10000	0	-10000	0	0
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.039	0.009	-10000	0	0	29	29
IRS1	0.04	0.008	-10000	0	0	22	22
p62DOK/RasGAP	0.05	0.079	-10000	0	-0.54	6	6
INS	0.043	0.014	0.082	13	-0.002	31	44
mol:PI-3-4-P2	-0.013	0.017	0.053	11	-0.09	8	19
GRB2	0.04	0.008	-10000	0	0	21	21
EIF4EBP1	0.009	0.085	0.15	111	-0.16	3	114
PTPRA	0.042	0.013	0.083	3	-0.049	1	4
PIK3CA	0.029	0.019	-10000	0	0	166	166
TC10/GTP/CIP4	0.046	0.029	-10000	0	-0.11	12	12
PDPK1	0.039	0.009	-10000	0	0	29	29
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.02	0.055	-10000	0	-0.16	27	27
Insulin Receptor/Insulin/IRS1	0.069	0.038	-10000	0	-0.099	8	8
Insulin Receptor/Insulin/IRS3	0.058	0.031	-10000	0	-0.12	4	4
Par3/Par6	0.069	0.049	-10000	0	-0.098	14	14

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.039	0.009	0	28	-9999	0	28
PI3K Class IB/PDE3B	0.039	0.009	-9999	0	0	28	28
PDE3B	0.039	0.009	-9999	0	0	28	28

×

Coregulation of Androgen receptor activity

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
NRIP1	0.035	0.016	-9999	-10000	0	0
SVIL	0.036	0.015	-9999	-10000	0	0
ZNF318	0.037	0.009	-9999	-0.032	2	2
JMJD2C	0.041	0.016	-9999	-10000	0	0
T-DHT/AR/Ubc9	0.037	0.06	-9999	-0.1	74	74
CARM1	0.036	0.014	-9999	0	71	71
PRDX1	0.039	0.009	-9999	0	31	31
PELP1	0.038	0.011	-9999	0	39	39
CTNNB1	0.04	0.01	-9999	-10000	0	0
AKT1	0.038	0.01	-9999	0	34	34
PTK2B	0.034	0.016	-9999	-10000	0	0
MED1	-0.001	0	-9999	-10000	0	0
MAK	0.033	0.014	-9999	-0.032	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.04	0.01	-9999	-10000	0	0
GSN	0.039	0.011	-9999	-10000	0	0
NCOA2	0.037	0.013	-9999	0	60	60
NCOA6	0.039	0.011	-9999	-10000	0	0
DNA-PK	0.049	0.067	-9999	-0.14	47	47
NCOA4	0.039	0.009	-9999	0	26	26
PIAS3	0.038	0.012	-9999	-10000	0	0
cell proliferation	0.019	0.042	-9999	-0.44	4	4
XRCC5	0.038	0.011	-9999	0	41	41
UBE3A	0.04	0.01	-9999	-10000	0	0
T-DHT/AR/SNURF	0.034	0.062	-9999	-0.11	74	74
FHL2	0.026	0.061	-9999	-0.58	4	4
RANBP9	0.039	0.012	-9999	-10000	0	0
JMJD1A	0.051	0.018	-9999	-0.14	1	1
CDK6	0.032	0.017	-9999	0	126	126
TGFB1I1	0.041	0.006	-9999	-10000	0	0
T-DHT/AR/CyclinD1	0.013	0.077	-9999	-0.12	125	125
XRCC6	0.036	0.014	-9999	0	69	69
T-DHT/AR	0.037	0.056	-9999	-0.099	68	68
CTDSP1	0.04	0.007	-9999	0	15	15
CTDSP2	0.038	0.009	-9999	-10000	0	0
BRCA1	0.035	0.016	-9999	-10000	0	0
TCF4	0.036	0.012	-9999	0	54	54
CDKN2A	0.028	0.019	-9999	0	167	167
SRF	0.043	0.019	-9999	-0.14	3	3
NKX3-1	0.014	0.083	-9999	-0.3	30	30
KLK3	0.004	0.048	-9999	-10000	0	0
TMF1	0.039	0.01	-9999	0	37	37
HNRNPA1	-0.001	0	-9999	-10000	0	0
AOF2	0.04	0.009	-9999	-10000	0	0
APPL1	-0.011	0.003	-9999	-10000	0	0
T-DHT/AR/Caspase 8	0.033	0.064	-9999	-0.11	86	86
AR	0.037	0.02	-9999	-0.042	1	1
UBA3	0	0	-9999	-10000	0	0
PATZ1	-0.001	0	-9999	-10000	0	0
PAWR	0.041	0.006	-9999	0	11	11
PRKDC	0.037	0.011	-9999	0	44	44
PA2G4	0.038	0.009	-9999	0	28	28
UBE2I	0.039	0.009	-9999	0	27	27
T-DHT/AR/Cyclin D3/CDK11 p58	0.034	0.056	-9999	-0.092	77	77
RPS6KA3	0.038	0.013	-9999	-10000	0	0
T-DHT/AR/ARA70	0.034	0.065	-9999	-0.1	88	88
LATS2	0.039	0.007	-9999	0	17	17
T-DHT/AR/PRX1	0.031	0.059	-9999	-0.094	88	88
Cyclin D3/CDK11 p58	0.028	0.015	-9999	-0.12	4	4
VAV3	0.034	0.017	-9999	-10000	0	0
KLK2	0.02	0.063	-9999	-0.3	16	16
CASP8	0.039	0.009	-9999	0	27	27
T-DHT/AR/TIF2/CARM1	0.043	0.07	-9999	-0.1	65	65
TMPRSS2	0.013	0.09	-9999	-0.31	34	34
CCND1	0.031	0.018	-9999	-10000	0	0
PIAS1	0.041	0.009	-9999	-10000	0	0
mol:T-DHT	0.005	0.005	-9999	-0.036	3	3
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.039	0.013	-9999	-10000	0	0
T-DHT/AR/CDK6	0.017	0.075	-9999	-0.11	117	117
CMTM2	0.036	0.013	-9999	0	60	60
SNURF	0.038	0.011	-9999	0	45	45
ZMIZ1	0.005	0.005	-9999	-0.036	3	3
CCND3	0.039	0.01	-9999	0	31	31
TGIF1	-0.001	0	-9999	-10000	0	0
FKBP4	0.037	0.014	-9999	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	-0.048	0.043	0.14	16	-10000	0	16
KIRREL	0.043	0.015	0.083	1	-10000	0	1
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.048	0.043	-10000	0	-0.14	16	16
PLCG1	0.038	0.011	-10000	0	0	43	43
ARRB2	0.038	0.011	-10000	0	0	46	46
WASL	0.04	0.007	-10000	0	0	18	18
Nephrin/NEPH1/podocin/CD2AP	0.073	0.067	-10000	0	-0.11	34	34
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.021	0.05	0.14	1	-0.15	30	31
FYN	0.006	0.065	0.16	68	-0.12	14	82
mol:Ca2+	0.075	0.06	-10000	0	-0.12	22	22
mol:DAG	0.076	0.061	0.21	1	-0.12	22	23
NPHS2	0.043	0.018	0.086	2	-0.042	15	17
mol:IP3	0.076	0.061	0.21	1	-0.12	22	23
regulation of endocytosis	0.053	0.056	-10000	0	-0.12	17	17
Nephrin/NEPH1/podocin/Cholesterol	0.062	0.047	0.18	1	-0.1	17	18
establishment of cell polarity	0.048	0.043	-10000	0	-0.14	16	16
Nephrin/NEPH1/podocin/NCK1-2	0.084	0.076	-10000	0	-0.11	37	37
Nephrin/NEPH1/beta Arrestin2	0.055	0.058	-10000	0	-0.12	17	17
NPHS1	0.037	0.021	0.085	4	-0.043	14	18
Nephrin/NEPH1/podocin	0.054	0.053	0.22	1	-0.12	15	16
TJP1	0.036	0.013	-10000	0	0	63	63
NCK1	0.036	0.014	-10000	0	0	70	70
NCK2	0.041	0.004	-10000	0	0	6	6
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.078	0.062	0.21	1	-0.12	22	23
CD2AP	0.037	0.013	-10000	0	0	62	62
Nephrin/NEPH1/podocin/GRB2	0.082	0.058	0.21	1	-0.12	16	17
GRB2	0.04	0.008	-10000	0	0	21	21
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	0.008	0.07	0.17	76	-0.12	2	78
cytoskeleton organization	0.017	0.054	0.22	10	-0.17	11	21
Nephrin/NEPH1	0.041	0.033	-10000	0	-0.092	17	17
Nephrin/NEPH1/ZO-1	0.054	0.06	-10000	0	-0.13	34	34

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.056	0.049	-10000	0	-0.11	22	22
fibroblast growth factor receptor signaling pathway	0.055	0.049	-10000	0	-0.11	22	22
LAMA1	0.033	0.016	-10000	0	0	104	104
PRNP	0.036	0.013	-10000	0	0	63	63
GPC1/SLIT2	0.018	0.07	-10000	0	-0.13	87	87
SMAD2	-0.02	0.036	0.19	9	-10000	0	9
GPC1/PrPc/Cu2+	0.04	0.041	-10000	0	-0.11	32	32
GPC1/Laminin alpha1	0.045	0.031	-10000	0	-0.13	6	6
TDGF1	0.04	0.006	-10000	0	0	13	13
CRIPTO/GPC1	0.056	0.018	-10000	0	-0.13	1	1
APP/GPC1	0.046	0.044	-10000	0	-0.13	27	27
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.017	0.027	0.19	6	-0.12	1	7
FLT1	0.039	0.009	-10000	0	0	28	28
GPC1/TGFB/TGFBR1/TGFBR2	0.067	0.042	-10000	0	-0.11	17	17
SERPINC1	0.04	0.008	-10000	0	0	19	19
FYN	-0.015	0.028	0.19	6	-0.12	1	7
FGR	-0.018	0.027	0.19	6	-0.12	1	7
positive regulation of MAPKKK cascade	0.002	0.074	0.2	19	-0.18	25	44
SLIT2	0.028	0.019	-10000	0	0	176	176
GPC1/NRG	0.05	0.025	-10000	0	-0.13	1	1
NRG1	0.036	0.014	-10000	0	0	74	74
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.049	0.023	-10000	0	-0.11	6	6
LYN	-0.016	0.025	0.19	5	-0.12	1	6
mol:Spermine	-0.01	0.002	-10000	0	-10000	0	0
cell growth	0.055	0.049	-10000	0	-0.11	22	22
BMP signaling pathway	-0.039	0.01	0	31	-10000	0	31
SRC	-0.018	0.025	0.19	5	-0.12	1	6
TGFBR1	0.039	0.008	-10000	0	0	23	23
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	0.036	0.014	-10000	0	0	67	67
GPC1	0.039	0.01	-10000	0	0	31	31
TGFBR1 (dimer)	0.039	0.008	-10000	0	0	23	23
VEGFA	0	0	-10000	0	-10000	0	0
BLK	-0.015	0.024	0.19	4	-0.12	1	5
HCK	-0.017	0.025	0.19	5	-10000	0	5
FGF2	0.039	0.01	-10000	0	0	33	33
FGFR1	0.033	0.017	-10000	0	0	112	112
VEGFR1 homodimer	0.039	0.009	-10000	0	0	28	28
TGFBR2	0.039	0.01	-10000	0	0	34	34
cell death	0.046	0.044	-10000	0	-0.13	27	27
ATIII/GPC1	0.055	0.019	-10000	0	-0.13	1	1
PLA2G2A/GPC1	0.05	0.027	-10000	0	-0.13	3	3
LCK	-0.018	0.027	0.19	6	-10000	0	6
neuron differentiation	0.049	0.025	-10000	0	-0.13	1	1
PrPc/Cu2+	0.02	0.036	-10000	0	-0.12	31	31
APP	0.038	0.011	-10000	0	0	41	41
TGFBR2 (dimer)	0.039	0.01	-10000	0	0	34	34

×

Signaling events mediated by VEGFR1 and VEGFR2

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.014	0.078	-10000	0	-0.15	93	93
AKT1	0.018	0.11	0.27	5	-0.31	20	25
PTK2B	-0.012	0.078	0.2	13	-0.31	7	20
VEGFR2 homodimer/Frs2	0.033	0.057	-10000	0	-0.37	4	4
CAV1	0.036	0.014	-10000	0	0	75	75
CALM1	0.039	0.009	-10000	0	0	26	26
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.031	0.058	-10000	0	-0.36	4	4
endothelial cell proliferation	0.036	0.098	0.28	15	-0.3	9	24
mol:Ca2+	0.023	0.068	0.26	3	-0.29	7	10
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.046	0.076	-10000	0	-0.21	20	20
RP11-342D11.1	-0.009	0.052	0.17	13	-0.32	5	18
CDH5	0.036	0.013	-10000	0	0	65	65
VEGFA homodimer	0.06	0.048	-10000	0	-0.11	27	27
SHC1	0.039	0.008	-10000	0	0	23	23
SHC2	0.036	0.014	-10000	0	0	67	67
HRAS/GDP	0.037	0.067	-10000	0	-0.24	10	10
SH2D2A	0.04	0.007	-10000	0	0	17	17
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.055	0.087	0.3	1	-0.37	6	7
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.036	0.055	-10000	0	-0.32	5	5
VEGFR1 homodimer	0.039	0.009	-10000	0	0	28	28
SHC/GRB2/SOS1	0.069	0.083	-10000	0	-0.25	11	11
GRB10	0.024	0.072	0.26	2	-0.35	8	10
PTPN11	0.039	0.009	-10000	0	0	29	29
GRB2	0.04	0.008	-10000	0	0	21	21
PAK1	0.036	0.013	-10000	0	0	65	65
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.051	0.086	-10000	0	-0.21	21	21
HRAS	0.039	0.01	-10000	0	0	31	31
VEGF/Rho/ROCK1/Integrin Complex	-0.016	0.11	-10000	0	-0.26	76	76
HIF1A	0.038	0.01	-10000	0	0	37	37
FRS2	0.038	0.011	-10000	0	0	41	41
oxygen and reactive oxygen species metabolic process	0.044	0.075	-10000	0	-0.21	20	20
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.04	0.008	-10000	0	0	22	22
Nck/Pak	0.036	0.056	-10000	0	-0.14	44	44
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.024	0.061	-10000	0	-0.27	7	7
mol:GDP	0.053	0.074	-10000	0	-0.24	11	11
mol:NADP	0.04	0.083	0.28	5	-0.33	7	12
eNOS/Hsp90	0.037	0.078	0.26	5	-0.31	7	12
PIK3R1	0.034	0.016	-10000	0	0	99	99
mol:IP3	0.023	0.069	0.26	3	-0.3	7	10
HIF1A/ARNT	0.046	0.044	-10000	0	-0.14	22	22
SHB	0.04	0.006	-10000	0	0	11	11
VEGFA	0.002	0.004	-10000	0	-0.037	6	6
VEGFC	0.036	0.014	-10000	0	0	69	69
FAK1/Vinculin	0.01	0.12	0.26	3	-0.3	37	40
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.04	0.006	-10000	0	0	13	13
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.023	0.087	-10000	0	-0.21	33	33
PTPN6	0.037	0.013	-10000	0	0	56	56
EPAS1	0.043	0.031	-10000	0	-0.27	3	3
mol:L-citrulline	0.04	0.083	0.28	5	-0.33	7	12
ITGAV	0.033	0.017	-10000	0	0	110	110
PIK3CA	0.029	0.019	-10000	0	0	166	166
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.053	0.068	-10000	0	-0.31	5	5
VEGFR2 homodimer/VEGFA homodimer	0.041	0.061	-10000	0	-0.28	8	8
VEGFR2/3 heterodimer	0.034	0.057	-10000	0	-0.33	5	5
VEGFB	0.038	0.011	-10000	0	0	40	40
MAPK11	-0.003	0.078	0.25	8	-0.32	10	18
VEGFR2 homodimer	0.019	0.044	-10000	0	-0.38	5	5
FLT1	0.039	0.009	-10000	0	0	28	28
NEDD4	0.039	0.016	-10000	0	-0.053	5	5
MAPK3	0.001	0.074	0.24	6	-0.27	8	14
MAPK1	0.001	0.074	0.24	7	-0.3	7	14
VEGFA145/NRP2	0.015	0.045	-10000	0	-0.11	54	54
VEGFR1/2 heterodimer	0.034	0.058	-10000	0	-0.29	7	7
KDR	0.019	0.044	-10000	0	-0.38	5	5
VEGFA165/NRP1/VEGFR2 homodimer	0.03	0.071	-10000	0	-0.21	19	19
SRC	0.039	0.009	-10000	0	0	28	28
platelet activating factor biosynthetic process	0.003	0.079	0.24	8	-0.3	7	15
PI3K	0.013	0.081	-10000	0	-0.31	9	9
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.026	0.062	-10000	0	-0.25	10	10
FES	0.024	0.068	0.26	3	-0.33	5	8
GAB1	0.02	0.083	0.26	2	-0.3	17	19
VEGFR2 homodimer/VEGFA homodimer/Src	0.035	0.053	-10000	0	-0.28	5	5
CTNNB1	0.039	0.01	-10000	0	0	32	32
SOS1	0.037	0.012	-10000	0	0	51	51
ARNT	0.037	0.012	-10000	0	0	50	50
eNOS/Caveolin-1	0.047	0.084	0.31	2	-0.35	6	8
VEGFR2 homodimer/VEGFA homodimer/Yes	0.028	0.062	-10000	0	-0.27	8	8
PI3K/GAB1	0.027	0.11	0.27	3	-0.31	20	23
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.048	0.082	-10000	0	-0.21	13	13
PRKACA	0.035	0.015	-10000	0	0	84	84
VEGFR2/3 heterodimer/VEGFC homodimer	0.051	0.066	-10000	0	-0.29	6	6
HSP90AA1	0	0	-10000	0	-10000	0	0
CDC42	0.024	0.068	0.26	3	-0.33	5	8
actin cytoskeleton reorganization	0.035	0.054	-10000	0	-0.32	5	5
PTK2	-0.007	0.11	0.23	1	-0.32	33	34
EDG1	0.023	0.065	0.24	2	-0.33	5	7
mol:DAG	0.023	0.069	0.26	3	-0.3	7	10
CaM/Ca2+	0.038	0.069	0.25	3	-0.26	8	11
MAP2K3	-0.006	0.063	0.18	28	-0.33	5	33
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.042	0.07	0.24	5	-0.34	9	14
PLCG1	0.023	0.069	0.26	3	-0.3	7	10
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.058	0.062	-10000	0	-0.27	5	5
IQGAP1	0.036	0.013	-10000	0	0	66	66
YES1	0.037	0.012	-10000	0	0	51	51
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.031	0.06	-10000	0	-0.28	7	7
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.034	0.053	-10000	0	-0.31	5	5
cell migration	0	0.13	0.26	4	-0.33	38	42
mol:PI-3-4-5-P3	0.013	0.078	-10000	0	-0.3	9	9
FYN	0.034	0.016	-10000	0	0	94	94
VEGFB/NRP1	0.028	0.064	0.22	2	-0.23	10	12
mol:NO	0.04	0.083	0.28	5	-0.33	7	12
PXN	0.04	0.006	-10000	0	0	10	10
HRAS/GTP	0.016	0.056	-10000	0	-0.23	11	11
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.025	0.061	-10000	0	-0.34	9	9
VHL	0.039	0.008	-10000	0	0	23	23
ITGB3	0.032	0.017	-10000	0	0	116	116
NOS3	0.04	0.088	0.29	4	-0.37	7	11
VEGFR2 homodimer/VEGFA homodimer/Sck	0.031	0.055	-10000	0	-0.31	5	5
RAC1	0.039	0.009	-10000	0	0	28	28
PRKCA	-0.006	0.067	0.18	35	-0.33	5	40
PRKCB	-0.002	0.066	0.18	37	-0.33	5	42
VCL	0.039	0.01	-10000	0	0	34	34
VEGFA165/NRP1	0.006	0.048	0.17	5	-0.26	8	13
VEGFR1/2 heterodimer/VEGFA homodimer	0.034	0.057	-10000	0	-0.28	7	7
VEGFA165/NRP2	0.015	0.045	-10000	0	-0.11	54	54
MAPKKK cascade	-0.02	0.07	0.18	24	-0.34	7	31
NRP2	0.034	0.015	-10000	0	0	93	93
VEGFC homodimer	0.036	0.014	-10000	0	0	69	69
NCK1	0.036	0.014	-10000	0	0	70	70
ROCK1	0.04	0.008	-10000	0	0	21	21
FAK1/Paxillin	0.012	0.12	0.26	3	-0.31	33	36
MAP3K13	0.017	0.065	0.26	3	-0.29	7	10
PDPK1	0.001	0.068	0.24	1	-0.28	7	8

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.015	0.005	-10000	0	-10000	0	0
ADCY5	-0.014	0.006	-10000	0	-10000	0	0
ADCY6	-0.015	0.004	-10000	0	-10000	0	0
ADCY7	-0.014	0.005	0	68	-10000	0	68
ADCY1	-0.015	0.004	0	39	-10000	0	39
ADCY2	-0.014	0.006	-10000	0	-10000	0	0
ADCY3	-0.015	0.004	0	44	-10000	0	44
ADCY8	-0.009	0.008	-10000	0	-10000	0	0
PRKCE	-0.01	0.002	0	28	-10000	0	28
ADCY9	-0.014	0.006	0	71	-10000	0	71
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	0.045	0.078	0.2	52	-0.2	5	57

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.036	0.014	-10000	0	0	69	69
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.001	0.11	0.44	13	-10000	0	13
IL27/IL27R/JAK1	0.08	0.11	-10000	0	-0.88	2	2
TBX21	0.006	0.1	0.38	4	-0.56	2	6
IL12B	0.041	0.008	-10000	0	0	18	18
IL12A	-0.006	0.006	0.012	26	-10000	0	26
IL6ST	0.036	0.017	-10000	0	-0.032	2	2
IL27RA/JAK1	0.05	0.098	-10000	0	-1	2	2
IL27	0.043	0.009	-10000	0	-0.032	2	2
TYK2	0.038	0.015	-10000	0	-0.033	2	2
T-helper cell lineage commitment	0.005	0.059	0.2	17	-0.18	29	46
T-helper 2 cell differentiation	-0.001	0.11	0.44	13	-10000	0	13
T cell proliferation during immune response	-0.001	0.11	0.44	13	-10000	0	13
MAPKKK cascade	0.001	0.11	-10000	0	-0.44	13	13
STAT3	0.038	0.011	-10000	0	0	41	41
STAT2	0.038	0.012	-10000	0	0	49	49
STAT1	0.034	0.016	-10000	0	0	102	102
IL12RB1	0.038	0.012	-10000	0	0	50	50
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.002	0.1	0.4	1	-0.52	2	3
IL27/IL27R/JAK2/TYK2	0.001	0.11	-10000	0	-0.44	13	13
positive regulation of T cell mediated cytotoxicity	0.001	0.11	-10000	0	-0.44	13	13
STAT1 (dimer)	0.062	0.12	-10000	0	-0.78	2	2
JAK2	0.035	0.018	-10000	0	-10000	0	0
JAK1	0.039	0.01	-10000	0	0	33	33
STAT2 (dimer)	0.019	0.13	-10000	0	-0.42	15	15
T cell proliferation	0.002	0.11	0.34	1	-0.42	13	14
IL12/IL12R/TYK2/JAK2	0.009	0.17	-10000	0	-0.72	25	25
IL17A	0.006	0.055	0.2	17	-0.18	26	43
mast cell activation	-0.001	0.11	0.44	13	-10000	0	13
IFNG	0.013	0.031	0.11	1	-0.092	9	10
T cell differentiation	-0.001	0.003	0.014	2	-0.016	5	7
STAT3 (dimer)	0.024	0.13	-10000	0	-0.42	14	14
STAT5A (dimer)	0.025	0.13	-10000	0	-0.43	13	13
STAT4 (dimer)	0.025	0.13	-10000	0	-0.42	13	13
STAT4	0.039	0.008	-10000	0	0	24	24
T cell activation	-0.008	0.01	-10000	0	-0.045	29	29
IL27R/JAK2/TYK2	0.048	0.096	-10000	0	-0.93	2	2
GATA3	0.015	0.12	0.64	17	-10000	0	17
IL18	-0.006	0.006	0.002	179	-10000	0	179
positive regulation of mast cell cytokine production	0.024	0.13	-10000	0	-0.41	14	14
IL27/EBI3	0.058	0.022	-10000	0	-10000	0	0
IL27RA	0.022	0.1	-10000	0	-1.1	2	2
IL6	0.034	0.016	-10000	0	0	100	100
STAT5A	0.038	0.01	-10000	0	0	36	36
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.009	0.034	0.49	2	-10000	0	2
IL1B	-0.007	0.006	0.002	145	-10000	0	145
EBI3	0.039	0.014	-10000	0	-10000	0	0
TNF	-0.008	0.005	0.006	60	-10000	0	60

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.047	0.044	-9999	-0.13	27	27
FBXW11	0.04	0.008	-9999	0	22	22
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.039	0.008	-9999	0	22	22
CHUK	0.038	0.011	-9999	0	46	46
NF kappa B2 p100/RelB	0.093	0.066	-9999	-0.11	32	32
NFKB1	0.036	0.013	-9999	0	66	66
MAP3K14	0.04	0.008	-9999	0	20	20
NF kappa B1 p50/RelB	0.043	0.048	-9999	-0.13	33	33
RELB	0.039	0.01	-9999	0	33	33
NFKB2	0.04	0.007	-9999	0	18	18
NF kappa B2 p52/RelB	0.05	0.023	-9999	-0.13	5	5
regulation of B cell activation	0.049	0.022	-9999	-0.13	5	5

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.088	0.048	-10000	0	-0.12	17	17
HDAC3	0.04	0.006	-10000	0	0	10	10
Ran/GTP/Exportin 1/HDAC4	-0.026	0.024	-10000	0	-0.11	32	32
GATA1/HDAC4	0.058	0.013	-10000	0	-10000	0	0
GATA1/HDAC5	0.059	0.012	-10000	0	-10000	0	0
GATA2/HDAC5	0.055	0.018	-10000	0	-10000	0	0
HDAC5/BCL6/BCoR	0.053	0.056	-10000	0	-0.12	33	33
HDAC9	0.036	0.014	-10000	0	0	74	74
Glucocorticoid receptor/Hsp90/HDAC6	0.044	0.038	-10000	0	-0.11	29	29
HDAC4/ANKRA2	0.049	0.031	-10000	0	-0.13	8	8
HDAC5/YWHAB	0.052	0.027	-10000	0	-0.13	6	6
NPC/RanGAP1/SUMO1/Ubc9	0.009	0.034	-10000	0	-0.14	25	25
GATA2	0.039	0.01	-10000	0	0	31	31
HDAC4/RFXANK	0.046	0.039	-10000	0	-0.13	18	18
BCOR	0.041	0.005	-10000	0	0	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.029	0.019	-10000	0	0	157	157
HDAC5	0.04	0.008	-10000	0	0	21	21
GNB1/GNG2	0.05	0.036	-10000	0	-0.13	16	16
Histones	-0.01	0.07	-10000	0	-0.19	37	37
ADRBK1	0.041	0.004	-10000	0	0	6	6
HDAC4	0.039	0.009	-10000	0	0	25	25
XPO1	0.039	0.01	-10000	0	0	35	35
HDAC5/ANKRA2	0.049	0.031	-10000	0	-0.13	8	8
HDAC4/Ubc9	0.055	0.019	-10000	0	-0.13	1	1
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.052	0.029	-10000	0	-0.13	7	7
TUBA1B	0	0	-10000	0	-10000	0	0
HDAC6	0.04	0.007	-10000	0	0	14	14
HDAC5/RFXANK	0.046	0.04	-10000	0	-0.13	20	20
CAMK4	0.037	0.012	-10000	0	0	55	55
Tubulin/HDAC6	0.051	0.016	-10000	0	-10000	0	0
SUMO1	0.04	0.007	-10000	0	0	14	14
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.038	0.011	-10000	0	0	45	45
GATA1	0.041	0.002	-10000	0	0	1	1
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.037	0.013	-10000	0	0	58	58
NR3C1	0.038	0.011	-10000	0	0	42	42
SUMO1/HDAC4	0.037	0.063	-10000	0	-0.18	17	17
SRF	0.038	0.01	-10000	0	0	37	37
HDAC4/YWHAB	0.052	0.027	-10000	0	-0.13	6	6
Tubulin	0.029	0.007	-10000	0	-10000	0	0
HDAC4/14-3-3 E	0.051	0.029	-10000	0	-0.13	7	7
GNB1	0.039	0.01	-10000	0	0	33	33
RANGAP1	0.037	0.012	-10000	0	0	54	54
BCL6/BCoR	0.038	0.051	-10000	0	-0.14	33	33
HDAC4/HDAC3/SMRT (N-CoR2)	0.073	0.032	-10000	0	-0.12	5	5
HDAC4/SRF	0.067	0.035	-10000	0	-0.12	2	2
HDAC4/ER alpha	0.038	0.053	-10000	0	-0.13	41	41
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.01	0.07	-10000	0	-0.19	37	37
cell motility	0.05	0.015	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.039	0.009	-10000	0	0	27	27
HDAC7/HDAC3	0.029	0.01	-10000	0	-0.12	2	2
BCL6	0.031	0.018	-10000	0	0	130	130
HDAC4/CaMK II delta B	0.039	0.009	-10000	0	0	25	25
Hsp90/HDAC6	0.03	0.005	-10000	0	-10000	0	0
ESR1	0.034	0.015	-10000	0	0	91	91
HDAC6/HDAC11	0.056	0.025	-10000	0	-0.13	7	7
Ran/GTP/Exportin 1	0.035	0.071	-10000	0	-0.18	36	36
NPC	0.019	0.022	-10000	0	-0.083	23	23
MEF2C	0.037	0.013	-10000	0	0	61	61
RAN	0.04	0.008	-10000	0	0	21	21
HDAC4/MEF2C	0.092	0.061	-10000	0	-0.11	16	16
GNG2	0.039	0.009	-10000	0	0	29	29
NCOR2	0.039	0.01	-10000	0	0	31	31
TUBB2A	0.039	0.01	-10000	0	0	33	33
HDAC11	0.04	0.008	-10000	0	0	21	21
HSP90AA1	0	0	-10000	0	-10000	0	0
RANBP2	0.039	0.009	-10000	0	0	30	30
ANKRA2	0.036	0.014	-10000	0	0	72	72
RFXANK	0.036	0.014	-10000	0	0	74	74
nuclear import	-0.036	0.039	0.18	12	-10000	0	12

×

Signaling events mediated by HDAC Class III

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
EP300	0.036	0.014	-10000	0	0	69	69
HDAC4	0.039	0.009	-10000	0	0	25	25
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.013	0.004	-10000	0	-10000	0	0
CDKN1A	0.016	0.051	0.37	4	-10000	0	4
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.039	0.008	-10000	0	0	23	23
FOXO3	0.002	0.04	0.25	14	-10000	0	14
FOXO1	0	0	-10000	0	-10000	0	0
FOXO4	0.005	0.033	-10000	0	-0.18	17	17
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.036	0.014	-10000	0	0	69	69
TAT	0.036	0.013	-10000	0	0	65	65
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.01	0.002	-10000	0	-10000	0	0
PPARGC1A	0.037	0.012	-10000	0	0	52	52
FHL2	0.04	0.008	-10000	0	0	19	19
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.045	0.042	-10000	0	-0.17	16	16
HIST2H4A	-0.013	0.004	-10000	0	-10000	0	0
SIRT1/FOXO3a	0.038	0.044	0.15	57	-0.2	2	59
SIRT1	0.037	0.007	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.071	0.033	-10000	0	-0.12	8	8
SIRT1/Histone H1b	0.002	0.09	-10000	0	-0.2	70	70
apoptosis	-0.062	0.046	0.14	16	-10000	0	16
SIRT1/PGC1A	0.045	0.025	-10000	0	-0.11	8	8
p53/SIRT1	-0.008	0.087	-10000	0	-0.14	152	152
SIRT1/FOXO4	0.007	0.076	-10000	0	-0.15	86	86
FOXO1/FHL2/SIRT1	0.045	0.024	-10000	0	-0.1	12	12
HIST1H1E	-0.004	0.068	-10000	0	-0.2	51	51
SIRT1/p300	0.044	0.041	-10000	0	-0.14	22	22
muscle cell differentiation	-0.018	0.023	0.11	9	-0.21	2	11
TP53	0.023	0.018	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.063	0.046	-10000	0	-0.15	16	16
CREBBP	0.037	0.012	-10000	0	0	53	53
MEF2D	0.04	0.007	-10000	0	0	18	18
HIV-1 Tat/SIRT1	0.048	0.029	-10000	0	-0.13	8	8
ACSS2	-0.021	0.009	0.04	1	-10000	0	1
SIRT1/PCAF/MYOD	0.018	0.023	0.21	2	-0.11	9	11

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.035	0.052	-10000	0	-0.4	5	5
VEGFR1 homodimer/NRP1	0.009	0.046	-10000	0	-0.39	5	5
mol:DAG	-0.024	0.039	0.19	1	-0.3	6	7
VEGFR1 homodimer/NRP1/VEGFR 121	0.008	0.042	-10000	0	-0.36	5	5
CaM/Ca2+	0.026	0.05	-10000	0	-0.28	7	7
HIF1A	0.045	0.033	-10000	0	-0.27	5	5
GAB1	0.037	0.013	-10000	0	0	58	58
AKT1	0.01	0.094	0.23	15	-0.27	16	31
PLCG1	-0.024	0.039	0.19	1	-0.31	6	7
NOS3	0.025	0.071	0.32	3	-0.26	10	13
CBL	0.04	0.008	-10000	0	0	20	20
mol:NO	0.029	0.076	0.3	7	-0.26	10	17
FLT1	0.018	0.044	-10000	0	-0.49	4	4
PGF	0.039	0.008	-10000	0	0	23	23
VEGFR1 homodimer/NRP2/VEGFR121	0.018	0.061	-10000	0	-0.3	8	8
CALM1	0.039	0.009	-10000	0	0	26	26
PIK3CA	0.029	0.019	-10000	0	0	166	166
eNOS/Hsp90	0.02	0.067	0.22	2	-0.25	9	11
endothelial cell proliferation	-0.003	0.062	0.29	2	-0.3	10	12
mol:Ca2+	-0.024	0.039	0.19	1	-0.3	6	7
MAPK3	-0.03	0.049	0.2	4	-0.25	9	13
MAPK1	-0.028	0.048	0.2	4	-0.25	8	12
PIK3R1	0.034	0.016	-10000	0	0	99	99
PLGF homodimer	0.039	0.008	-10000	0	0	23	23
PRKACA	0.035	0.015	-10000	0	0	84	84
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.036	0.014	-10000	0	0	75	75
VEGFA homodimer	0	0	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.009	0.046	-10000	0	-0.39	5	5
platelet activating factor biosynthetic process	-0.027	0.056	0.32	1	-0.28	6	7
PI3K	0.037	0.077	-10000	0	-0.24	15	15
PRKCA	-0.02	0.046	0.22	4	-0.26	8	12
PRKCB	-0.022	0.036	0.18	1	-0.28	6	7
VEGFR1 homodimer/PLGF homodimer	0.035	0.053	-10000	0	-0.4	5	5
VEGFA	0	0	-10000	0	-10000	0	0
VEGFB	0.038	0.011	-10000	0	0	40	40
mol:IP3	-0.024	0.039	0.19	1	-0.3	6	7
RASA1	-0.021	0.045	0.19	2	-0.32	7	9
NRP2	0.034	0.015	-10000	0	0	93	93
VEGFR1 homodimer	0.018	0.044	-10000	0	-0.49	4	4
VEGFB homodimer	0.038	0.011	-10000	0	0	40	40
NCK1	0.036	0.014	-10000	0	0	70	70
eNOS/Caveolin-1	0.045	0.083	0.32	6	-0.26	10	16
PTPN11	0.039	0.009	-10000	0	0	29	29
mol:PI-3-4-5-P3	0.036	0.076	-10000	0	-0.23	16	16
mol:L-citrulline	0.029	0.076	0.3	7	-0.26	10	17
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.041	0.065	-10000	0	-0.27	9	9
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.023	0.058	-10000	0	-0.28	10	10
CD2AP	0.037	0.013	-10000	0	0	62	62
PI3K/GAB1	0.042	0.085	-10000	0	-0.24	16	16
PDPK1	0.007	0.094	0.18	93	-0.3	7	100
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.028	0.054	-10000	0	-0.28	9	9
mol:NADP	0.029	0.076	0.3	7	-0.26	10	17
HSP90AA1	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.039	0.063	-10000	0	-0.27	9	9
VEGFR1 homodimer/NRP2	0.028	0.057	-10000	0	-0.34	8	8

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.014	0.17	-10000	0	-0.69	14	14
NCK1/PAK1/Dok-R	-0.031	0.073	-10000	0	-0.33	14	14
NCK1/Dok-R	0.051	0.097	-10000	0	-0.87	2	2
PIK3CA	0.028	0.019	-10000	0	0	166	166
mol:beta2-estradiol	-0.008	0.008	-10000	0	-10000	0	0
RELA	0.04	0.006	-10000	0	0	10	10
SHC1	0.04	0.009	-10000	0	0	23	23
Rac/GDP	0.029	0.009	-10000	0	-0.12	1	1
F2	0.011	0.037	-10000	0	-0.082	1	1
TNIP2	0.038	0.011	-10000	0	0	43	43
NF kappa B/RelA	0.075	0.1	-10000	0	-0.83	2	2
FN1	0.021	0.021	-10000	0	0	268	268
PLD2	0.032	0.079	-10000	0	-0.89	2	2
PTPN11	0.039	0.009	-10000	0	0	29	29
GRB14	0.038	0.012	-10000	0	0	49	49
ELK1	0.033	0.081	-10000	0	-0.84	2	2
GRB7	0.037	0.013	-10000	0	0	57	57
PAK1	0.036	0.013	-10000	0	0	65	65
Tie2/Ang1/alpha5/beta1 Integrin	0.023	0.11	-10000	0	-0.86	2	2
CDKN1A	0.012	0.19	-10000	0	-0.62	38	38
ITGA5	0.036	0.013	-10000	0	0	64	64
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.056	0.096	-10000	0	-0.87	2	2
CRK	0.038	0.012	-10000	0	0	49	49
mol:NO	0.023	0.15	-10000	0	-0.52	15	15
PLG	0.031	0.077	-10000	0	-0.89	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.027	0.14	-10000	0	-0.75	6	6
GRB2	0.04	0.008	-10000	0	0	21	21
PIK3R1	0.034	0.016	-10000	0	0	99	99
ANGPT2	-0.045	0.28	-10000	0	-1	37	37
BMX	0.031	0.078	-10000	0	-0.89	2	2
ANGPT1	0.013	0.047	-10000	0	-10000	0	0
tube development	-0.002	0.21	-10000	0	-0.7	38	38
ANGPT4	0.035	0.02	-10000	0	-0.014	71	71
response to hypoxia	0.001	0.008	0.033	1	-0.062	2	3
Tie2/Ang1/GRB14	0.051	0.089	-10000	0	-0.91	2	2
alpha5/beta1 Integrin	0.043	0.046	-10000	0	-0.13	29	29
FGF2	0.039	0.011	-10000	0	0	33	33
STAT5A (dimer)	0.015	0.24	-10000	0	-0.8	38	38
mol:L-citrulline	0.023	0.15	-10000	0	-0.52	15	15
AGTR1	0.032	0.025	-10000	0	-0.018	93	93
MAPK14	0.041	0.13	-10000	0	-1	4	4
Tie2/SHP2	0.039	0.11	-10000	0	-0.76	3	3
TEK	0.028	0.1	-10000	0	-0.8	3	3
RPS6KB1	0.014	0.16	-10000	0	-0.65	12	12
Angiotensin II/AT1	0.025	0.024	-10000	0	-0.059	33	33
Tie2/Ang1/GRB2	0.056	0.091	-10000	0	-0.91	2	2
MAPK3	0.026	0.076	-10000	0	-0.84	2	2
MAPK1	0.028	0.079	-10000	0	-0.84	2	2
Tie2/Ang1/GRB7	0.053	0.089	-10000	0	-0.91	2	2
NFKB1	0.036	0.013	-10000	0	0	66	66
MAPK8	0.031	0.081	-10000	0	-0.89	2	2
PI3K	0.011	0.16	-10000	0	-0.93	6	6
FES	0.043	0.11	-10000	0	-1	2	2
Crk/Dok-R	0.058	0.094	-10000	0	-0.87	2	2
Tie2/Ang1/ABIN2	0.054	0.09	-10000	0	-0.91	2	2
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.018	0.16	-10000	0	-0.61	15	15
STAT5A	0.039	0.01	-10000	0	0	36	36
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.054	0.18	-10000	0	-0.63	9	9
Tie2/Ang2	-0.012	0.27	-10000	0	-0.95	38	38
Tie2/Ang1	0.039	0.081	-10000	0	-0.94	2	2
FOXO1	0.012	0.18	-10000	0	-0.61	37	37
ELF1	0.047	0.018	-10000	0	-0.13	2	2
ELF2	0.036	0.079	-10000	0	-0.89	2	2
mol:Choline	0.032	0.077	-10000	0	-0.87	2	2
cell migration	-0.017	0.047	-10000	0	-0.19	13	13
FYN	-0.01	0.23	-10000	0	-0.8	38	38
DOK2	0.032	0.017	-10000	0	0	118	118
negative regulation of cell cycle	0.015	0.17	-10000	0	-0.56	38	38
ETS1	0.041	0.021	-10000	0	-10000	0	0
PXN	0.053	0.16	0.39	2	-0.55	9	11
ITGB1	0.038	0.01	-10000	0	0	36	36
NOS3	0.02	0.16	-10000	0	-0.59	14	14
RAC1	0.039	0.009	-10000	0	0	28	28
TNF	0.048	0.013	-10000	0	-10000	0	0
MAPKKK cascade	0.032	0.077	-10000	0	-0.87	2	2
RASA1	0.037	0.013	-10000	0	0	56	56
Tie2/Ang1/Shc	0.058	0.091	-10000	0	-0.91	2	2
NCK1	0.036	0.014	-10000	0	0	70	70
vasculogenesis	0.025	0.14	-10000	0	-0.47	15	15
mol:Phosphatidic acid	0.032	0.077	-10000	0	-0.87	2	2
mol:Angiotensin II	0	0.008	-10000	0	-0.033	30	30
mol:NADP	0.023	0.15	-10000	0	-0.52	15	15
Rac1/GTP	0.028	0.15	-10000	0	-0.65	9	9
MMP2	0.032	0.088	-10000	0	-0.89	2	2

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.038	0.012	-10000	0	0	49	49
Ran/GTP/Exportin 1/HDAC4	-0.028	0.033	-10000	0	-0.14	33	33
MDM2/SUMO1	0.036	0.063	-10000	0	-0.18	19	19
HDAC4	0.039	0.009	-10000	0	0	25	25
Ran/GTP/Exportin 1/HDAC1	-0.031	0.039	-10000	0	-0.14	46	46
SUMO1	0.04	0.007	-10000	0	0	14	14
NPC/RanGAP1/SUMO1	0.007	0.033	-10000	0	-0.14	25	25
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	-0.001	0.031	-10000	0	-0.14	12	12
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.04	0.008	-10000	0	0	21	21
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.039	0.009	-10000	0	0	30	30
SUMO1/HDAC4	0.037	0.063	-10000	0	-0.18	17	17
SUMO1/HDAC1	0.034	0.066	-10000	0	-0.18	25	25
RANGAP1	0.037	0.012	-10000	0	0	54	54
MDM2/SUMO1/SUMO1	0.083	0.053	-10000	0	-0.12	17	17
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.009	0.034	-10000	0	-0.14	25	25
Ran/GTP	0.02	0.057	-10000	0	-0.15	35	35
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.038	0.01	-10000	0	0	36	36
UBE2I	0.039	0.009	-10000	0	0	27	27
Ran/GTP/Exportin 1	0.015	0.066	0.2	8	-0.18	36	44
NPC	0.019	0.022	-10000	0	-0.083	23	23
PIAS2	0.038	0.011	-10000	0	0	42	42
PIAS1	0.039	0.008	-10000	0	0	24	24
EntrezGene:9972	0	0	-10000	0	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.041	0.004	-9999	0	6	6
Aurora C/Aurora B/INCENP	0.06	0.045	-9999	-0.1	26	26
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.003	0.068	-9999	-0.38	16	16
AURKB	0.035	0.014	-9999	0	78	78
AURKC	0.039	0.01	-9999	0	34	34

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	0.007	0.11	-10000	0	-0.81	9	9
MKNK1	0.04	0.007	-10000	0	0	15	15
MAPK14	0.041	0.052	0.17	1	-0.13	32	33
ATF2/c-Jun	-0.026	0.1	-10000	0	-0.31	44	44
MAPK11	0.029	0.051	-10000	0	-0.13	29	29
MITF	0.018	0.06	-10000	0	-0.29	14	14
MAPKAPK5	0.018	0.057	-10000	0	-0.26	16	16
KRT8	0.014	0.061	-10000	0	-0.22	25	25
MAPKAPK3	0.04	0.006	-10000	0	0	11	11
MAPKAPK2	0.04	0.007	-10000	0	0	14	14
p38alpha-beta/CK2	0.04	0.075	-10000	0	-0.28	14	14
CEBPB	0.02	0.053	-10000	0	-0.29	10	10
SLC9A1	0.019	0.054	-10000	0	-0.28	13	13
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.012	0.074	0.23	1	-0.24	28	29
p38alpha-beta/MNK1	0.051	0.075	-10000	0	-0.3	9	9
JUN	-0.028	0.1	-10000	0	-0.31	44	44
PPARGC1A	0.02	0.054	-10000	0	-0.28	12	12
USF1	0.018	0.056	-10000	0	-0.26	15	15
RAB5/GDP/GDI1	-0.001	0.078	-10000	0	-0.19	30	30
NOS2	0.014	0.051	-10000	0	-0.28	12	12
DDIT3	0.015	0.059	-10000	0	-0.22	23	23
RAB5A	0.04	0.006	-10000	0	0	13	13
HSPB1	0.002	0.05	0.3	2	-0.23	15	17
p38alpha-beta/HBP1	0.042	0.081	-10000	0	-0.26	13	13
CREB1	-0.012	0.1	-10000	0	-0.2	107	107
RAB5/GDP	0.029	0.012	-10000	0	-0.12	3	3
EIF4E	-0.01	0.056	0.2	11	-0.29	8	19
RPS6KA4	0.019	0.055	-10000	0	-0.27	13	13
PLA2G4A	-0.01	0.054	0.24	5	-0.32	9	14
GDI1	0.016	0.06	-10000	0	-0.25	20	20
TP53	0.002	0.058	-10000	0	-0.35	10	10
RPS6KA5	0.017	0.058	-10000	0	-0.25	18	18
ESR1	0.007	0.072	-10000	0	-0.23	38	38
HBP1	0.038	0.011	-10000	0	0	43	43
MEF2C	0.014	0.067	-10000	0	-0.28	19	19
MEF2A	0.017	0.057	-10000	0	-0.26	16	16
EIF4EBP1	-0.008	0.094	-10000	0	-0.2	94	94
KRT19	0.008	0.076	-10000	0	-0.23	39	39
ELK4	0.018	0.055	-10000	0	-0.27	14	14
ATF6	0.018	0.055	-10000	0	-0.25	15	15
ATF1	-0.011	0.098	-10000	0	-0.3	18	18
p38alpha-beta/MAPKAPK2	0.051	0.075	-10000	0	-0.26	11	11
p38alpha-beta/MAPKAPK3	0.052	0.074	-10000	0	-0.29	9	9

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.01	0.001	0	11	-10000	0	11
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.056	0.02	-10000	0	-0.13	2	2
STXBP1	0.038	0.011	-10000	0	0	42	42
ACh/CHRNA1	0.027	0.025	0.091	1	-0.048	39	40
RAB3GAP2/RIMS1/UNC13B	0.069	0.041	-10000	0	-0.12	15	15
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.039	0.009	-10000	0	0	29	29
mol:ACh	0.002	0.023	0.072	24	-0.085	4	28
RAB3GAP2	0.039	0.01	-10000	0	0	35	35
STX1A/SNAP25/VAMP2	0.053	0.057	0.18	1	-0.1	24	25
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.027	0.025	0.091	1	-0.048	39	40
UNC13B	0.04	0.007	-10000	0	0	15	15
CHRNA1	0.037	0.013	-10000	0	0	57	57
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0.028	0.025	0.091	1	-0.048	39	40
SNAP25	0.006	0.002	-10000	0	0	58	58
VAMP2	0.005	0.002	-10000	0	0	69	69
SYT1	0.038	0.011	-10000	0	0	42	42
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.033	0.011	-10000	0	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.053	0.057	0.18	1	-0.1	24	25

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.019	0.02	0.076	5	-0.092	3	8
NFATC2	0.019	0.02	0.084	1	-0.11	3	4
NFATC3	0.02	0.02	0.077	6	-0.082	4	10
CD40LG	0.03	0.1	0.3	20	-0.24	1	21
PTGS2	0.011	0.093	0.33	12	-0.26	6	18
JUNB	0.029	0.019	-10000	0	0	159	159
CaM/Ca2+/Calcineurin A alpha-beta B1	0.032	0.016	-10000	0	-0.12	3	3
CaM/Ca2+	0.032	0.016	-10000	0	-0.12	3	3
CALM1	0.041	0.011	-10000	0	-0.002	28	28
JUN	0.038	0.016	0.1	1	-0.035	1	2
mol:Ca2+	0.001	0.003	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.027	0.011	0.067	1	-0.1	2	3
FOSL1	0.04	0.007	-10000	0	0	18	18
CREM	0.039	0.007	-10000	0	0	19	19
Jun/NFAT1-c-4/p21SNFT	0.054	0.066	0.22	3	-10000	0	3
FOS	0.028	0.022	0.1	1	0	201	202
IFNG	0.02	0.094	0.31	11	-0.24	1	12
AP-1/NFAT1-c-4	0.082	0.11	-10000	0	-0.23	3	3
FASLG	0.027	0.1	0.31	16	-0.24	2	18
NFAT1-c-4/ICER1	0.054	0.056	0.21	7	-10000	0	7
IL2RA	0.027	0.1	0.33	17	-0.24	2	19
FKBP12/FK506	0.028	0.012	-10000	0	-0.12	2	2
CSF2	0.029	0.1	0.3	19	-0.24	1	20
JunB/Fra1/NFAT1-c-4	0.046	0.072	0.23	3	-0.18	3	6
IL4	0.029	0.1	0.3	18	-0.24	1	19
IL2	-0.024	0.2	-10000	0	-0.87	30	30
IL3	0.027	0.12	-10000	0	-0.6	19	19
FKBP1A	0.038	0.011	-10000	0	0	44	44
BATF3	0	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.045	0.008	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.046	0.01	-10000	0	-0.051	3	3
NFATC2	0.046	0.18	0.41	5	-0.38	38	43
NFATC3	0.071	0.066	0.29	26	-0.24	3	29
CD40LG	0.083	0.15	0.5	4	-0.69	2	6
ITCH	0.022	0.053	0.2	5	-0.2	21	26
CBLB	0.019	0.061	0.2	6	-0.26	20	26
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	0.043	0.14	0.37	1	-0.5	5	6
JUNB	0.029	0.019	-10000	0	0	159	159
CaM/Ca2+/Calcineurin A alpha-beta B1	0.044	0.048	-10000	0	-0.18	22	22
T cell anergy	0.002	0.066	0.25	5	-0.28	17	22
TLE4	0.007	0.15	0.28	3	-0.41	44	47
Jun/NFAT1-c-4/p21SNFT	0.085	0.15	-10000	0	-0.7	2	2
AP-1/NFAT1-c-4	0.09	0.19	-10000	0	-0.76	2	2
IKZF1	0.021	0.11	0.22	17	-0.25	38	55
T-helper 2 cell differentiation	0.034	0.14	0.45	1	-0.49	1	2
AP-1/NFAT1	0.035	0.14	0.33	2	-0.25	39	41
CALM1	0.042	0.034	-10000	0	-0.11	23	23
EGR2	0.061	0.16	0.58	6	-1.1	2	8
EGR3	0.055	0.13	0.58	5	-0.52	1	6
NFAT1/FOXP3	0.057	0.14	0.32	3	-0.27	35	38
EGR1	0.027	0.021	0.074	1	0	190	191
JUN	0.04	0.026	0.14	2	-0.054	4	6
EGR4	0.041	0.009	-10000	0	-0.035	2	2
mol:Ca2+	0.005	0.022	-10000	0	-0.099	22	22
GBP3	-0.021	0.21	0.32	21	-0.45	91	112
FOSL1	0.04	0.007	-10000	0	0	18	18
NFAT1-c-4/MAF/IRF4	0.09	0.15	-10000	0	-0.68	2	2
DGKA	0.025	0.12	0.29	7	-0.3	33	40
CREM	0.039	0.008	-10000	0	-0.002	20	20
NFAT1-c-4/PPARG	0.086	0.14	-10000	0	-0.69	2	2
CTLA4	0.023	0.1	-10000	0	-0.23	32	32
NFAT1-c-4 (dimer)/EGR1	0.062	0.15	-10000	0	-0.75	2	2
NFAT1-c-4 (dimer)/EGR4	0.094	0.15	-10000	0	-0.72	2	2
FOS	0.029	0.029	0.13	3	-0.042	7	10
IFNG	0.033	0.13	-10000	0	-0.49	7	7
T cell activation	0.054	0.12	0.6	1	-10000	0	1
MAF	0.036	0.015	-10000	0	0	80	80
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.064	0.12	0.53	2	-0.5	22	24
TNF	0.048	0.13	0.46	2	-0.69	2	4
FASLG	0.055	0.16	0.7	1	-1	3	4
TBX21	0.046	0.013	0.093	1	-10000	0	1
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	0.037	0.018	-10000	0	-0.12	1	1
PTPN1	0.028	0.12	0.29	7	-0.27	29	36
NFAT1-c-4/ICER1	0.087	0.15	-10000	0	-0.72	2	2
GATA3	0.041	0.011	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.035	0.13	-10000	0	-0.49	7	7
IL2RA	0.05	0.15	-10000	0	-0.5	6	6
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.023	0.12	0.27	2	-0.3	30	32
E2F1	0.031	0.05	-10000	0	-0.18	27	27
PPARG	0.039	0.01	-10000	0	-10000	0	0
SLC3A2	0.024	0.13	0.29	5	-0.3	36	41
IRF4	0.038	0.012	-10000	0	0	46	46
PTGS2	0.055	0.14	0.69	1	-0.72	2	3
CSF2	0.079	0.15	0.5	4	-0.69	2	6
JunB/Fra1/NFAT1-c-4	0.076	0.15	-10000	0	-0.69	2	2
IL4	0.033	0.14	-10000	0	-0.5	1	1
IL5	0.078	0.15	0.49	3	-0.69	2	5
IL2	0.054	0.12	0.6	1	-10000	0	1
IL3	0.036	0.078	-10000	0	-0.41	13	13
RNF128	0.022	0.042	0.2	4	-0.15	22	26
NFATC1	0.064	0.12	0.5	22	-0.53	2	24
CDK4	-0.077	0.29	0.47	3	-1.2	28	31
PTPRK	0.011	0.15	0.28	3	-0.39	45	48
IL8	0.048	0.14	0.58	3	-0.57	3	6
POU2F1	0.046	0.008	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	0.06	0.035	-9999	0	-0.096	15	15
MAPK9	0.009	0.002	-9999	0	0	39	39
adrenocorticotropin secretion	-0.01	0.003	0	42	-10000	0	42
GNB1/GNG2	0.046	0.031	-9999	0	-0.11	16	16
GNB1	0.039	0.01	-9999	0	0	33	33
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	0	-10000	0	0
mol:GDP	0	0	-9999	0	-10000	0	0
MAPK14	0.009	0.002	-9999	0	0	20	20
Gs family/GTP	0.025	0.005	-9999	0	-10000	0	0
EntrezGene:2778	0	0	-9999	0	-10000	0	0
vasopressin secretion	0	0	-9999	0	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	0	-10000	0	0
glutamate secretion	0.002	0	-9999	0	-10000	0	0
GNAL	0.04	0.008	-9999	0	0	22	22
GNG2	0.039	0.009	-9999	0	0	29	29
CRH	0.038	0.011	-9999	0	0	42	42
mol:cortisol	0	0	-9999	0	-10000	0	0
MAPK8	0.009	0.002	-9999	0	0	29	29
MAPK11	0.007	0.004	-9999	0	0	157	157

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.037	0.017	-10000	0	-0.13	3	3
PDGFRB	0.037	0.014	-10000	0	0	65	65
SPHK1	0.011	0.085	-10000	0	-0.63	9	9
mol:S1P	0.009	0.076	-10000	0	-0.53	9	9
S1P1/S1P/Gi	0.025	0.081	-10000	0	-0.31	18	18
GNAO1	0.035	0.017	-10000	0	-0.003	92	92
PDGFB-D/PDGFRB/PLCgamma1	0.013	0.1	0.25	7	-0.27	31	38
PLCG1	0.01	0.087	0.21	11	-0.3	19	30
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.037	0.014	-10000	0	0	65	65
GNAI2	0.04	0.012	-10000	0	-0.014	22	22
GNAI3	0.038	0.015	-10000	0	-0.006	54	54
GNAI1	0.034	0.018	-10000	0	-0.002	100	100
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	0.024	0.016	-10000	0	-0.12	3	3
S1P1/S1P	0.021	0.068	0.2	1	-0.33	11	12
negative regulation of cAMP metabolic process	0.025	0.08	-10000	0	-0.3	18	18
MAPK3	0.011	0.11	-10000	0	-0.47	14	14
calcium-dependent phospholipase C activity	0	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.029	0.009	-10000	0	-0.12	1	1
RhoA/GDP	0.029	0.014	-10000	0	-0.12	4	4
KDR	0.043	0.01	-10000	0	-10000	0	0
PLCB2	0.016	0.064	-10000	0	-0.31	10	10
RAC1	0.039	0.009	-10000	0	0	28	28
RhoA/GTP	0.019	0.06	-10000	0	-0.28	12	12
receptor internalization	0.02	0.064	0.19	2	-0.31	11	13
PTGS2	0.003	0.15	0.34	1	-0.81	11	12
Rac1/GTP	0.019	0.06	-10000	0	-0.29	11	11
RHOA	0.04	0.006	-10000	0	0	13	13
VEGFA	0.004	0.002	-10000	0	-10000	0	0
negative regulation of T cell proliferation	0.025	0.08	-10000	0	-0.3	18	18
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.038	0.015	-10000	0	-0.005	55	55
MAPK1	0.014	0.097	0.26	1	-0.44	12	13
S1P1/S1P/PDGFB-D/PDGFRB	0.032	0.076	0.23	2	-0.27	13	15
ABCC1	0.04	0.009	-10000	0	0	27	27

×

Arf6 trafficking events

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
SLC2A4	0.039	0.01	-10000	0	0	35	35
CLTC	0.011	0.086	-10000	0	-0.46	11	11
calcium ion-dependent exocytosis	0.016	0.046	0.18	2	-0.19	9	11
Dynamin 2/GTP	0.021	0.041	-10000	0	-0.11	44	44
EXOC4	0.038	0.011	-10000	0	0	41	41
CD59	0.009	0.057	-10000	0	-0.35	10	10
CPE	0.012	0.013	-10000	0	-0.11	4	4
CTNNB1	0.039	0.01	-10000	0	0	32	32
membrane fusion	0.004	0.033	0.11	2	-0.15	12	14
CTNND1	-0.009	0.066	0.17	50	-0.2	3	53
DNM2	0.036	0.014	-10000	0	0	72	72
mol:PI-4-5-P2	0.015	0.053	0.18	3	-0.22	12	15
TSHR	0.014	0.015	-10000	0	-0.11	7	7
INS	0.004	0.1	-10000	0	-0.45	26	26
BIN1	0.04	0.007	-10000	0	0	18	18
mol:Choline	0.004	0.033	0.11	2	-0.15	12	14
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.014	0.013	-10000	0	-0.11	5	5
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.04	0.007	-10000	0	0	16	16
mol:Ca2+	0.021	0.041	-10000	0	-0.11	44	44
JUP	0.008	0.058	-10000	0	-0.35	9	9
ASAP2/amphiphysin II	0.047	0.023	-10000	0	-0.096	11	11
ARF6/GTP	0.028	0.019	-10000	0	-0.12	8	8
CDH1	0.006	0.063	-10000	0	-0.38	10	10
clathrin-independent pinocytosis	0.028	0.019	-10000	0	-0.12	8	8
MAPK8IP3	0.039	0.009	-10000	0	0	29	29
positive regulation of endocytosis	0.028	0.019	-10000	0	-0.12	8	8
EXOC2	0.038	0.011	-10000	0	0	41	41
substrate adhesion-dependent cell spreading	0.012	0.1	-10000	0	-0.27	46	46
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.039	0.009	-10000	0	0	30	30
regulation of calcium-dependent cell-cell adhesion	-0.031	0.081	0.33	12	-10000	0	12
positive regulation of phagocytosis	0.015	0.015	-10000	0	-0.11	7	7
ARF6/GTP/JIP3	0.05	0.024	-10000	0	-0.11	8	8
ACAP1	0.004	0.033	-10000	0	-0.17	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.012	0.057	-10000	0	-0.33	10	10
clathrin heavy chain/ACAP1	0.012	0.074	0.25	1	-0.37	11	12
JIP4/KLC1	0.045	0.029	-10000	0	-0.097	19	19
EXOC1	0.038	0.011	-10000	0	0	46	46
exocyst	0.011	0.11	-10000	0	-0.28	46	46
RALA/GTP	0.027	0.02	-10000	0	-0.12	9	9
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.047	0.032	-10000	0	-0.11	19	19
receptor recycling	0.028	0.019	-10000	0	-0.12	8	8
CTNNA1	-0.009	0.065	0.17	48	-0.2	3	51
NME1	0.014	0.013	-10000	0	-0.11	5	5
clathrin coat assembly	0.012	0.086	-10000	0	-0.46	11	11
IL2RA	0.012	0.055	-10000	0	-0.33	9	9
VAMP3	0.015	0.015	-10000	0	-0.11	7	7
GLUT4/clathrin heavy chain/ACAP1	0.035	0.079	-10000	0	-0.36	10	10
EXOC6	0.038	0.011	-10000	0	0	46	46
PLD1	0	0.048	-10000	0	-0.19	28	28
PLD2	0.014	0.025	-10000	0	-0.19	3	3
EXOC5	0.04	0.008	-10000	0	0	20	20
PIP5K1C	0.011	0.049	0.18	2	-0.22	11	13
SDC1	0.01	0.058	-10000	0	-0.35	10	10
ARF6/GDP	0.026	0.038	-10000	0	-0.11	35	35
EXOC7	0.04	0.007	-10000	0	0	18	18
E-cadherin/beta catenin	0.034	0.084	-10000	0	-0.34	12	12
mol:Phosphatidic acid	0.004	0.033	0.11	2	-0.15	12	14
endocytosis	-0.046	0.023	0.096	11	-10000	0	11
SCAMP2	0.039	0.009	-10000	0	0	25	25
ADRB2	0.005	0.084	0.24	2	-0.43	11	13
EXOC3	0.037	0.012	-10000	0	0	55	55
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.025	0.045	0.19	4	-0.11	44	48
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	0.006	0.083	0.25	1	-0.43	11	12
RALA	0.04	0.008	-10000	0	0	19	19
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.017	0.086	-10000	0	-0.37	12	12

×

Arf1 pathway

Figure S127. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S127. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.018	0.042	0.15	49	-0.12	1	50
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.016	0.035	0.12	6	-0.16	3	9
AP2	0.039	0.043	-10000	0	-0.13	21	21
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.051	0.018	-10000	0	-0.11	1	1
CLTB	0.04	0.008	-10000	0	0	22	22
coatomer protein complex/ARF1/GTP/ER cargo protein	0.02	0.03	-10000	0	-0.15	13	13
CD4	0.032	0.017	-10000	0	0	121	121
CLTA	0.04	0.006	-10000	0	0	10	10
mol:GTP	-0.003	0.003	0.013	5	-0.02	1	6
ARFGAP1	-0.009	0.003	0	56	-10000	0	56
mol:PI-4-5-P2	0.009	0.014	0.079	15	-10000	0	15
ARF1/GTP	0.021	0.012	0.078	1	-0.14	1	2
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.022	0.05	0.17	45	-0.17	4	49
mol:Choline	0.008	0.014	0.079	15	-10000	0	15
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.039	0.012	-10000	0	0	45	45
DDEF1	0.004	0.009	0.079	6	-10000	0	6
ARF1/GDP	0.006	0.015	0.058	2	-0.087	8	10
AP2M1	0.032	0.017	-10000	0	0	125	125
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.009	0.017	0.049	11	-0.1	2	13
Rac/GTP	0.029	0.01	-10000	0	-0.13	1	1
ARF1/GTP/GGA3/ARF-GAP1	0.046	0.024	-10000	0	-0.1	1	1
ARFIP2	0.033	0.021	-10000	0	-0.039	36	36
COPA	0.039	0.009	-10000	0	0	26	26
RAC1	0.039	0.009	-10000	0	0	28	28
ARF1/GTP/coatomer protein complex	0.015	0.038	0.14	2	-0.2	10	12
ARF1/GTP/ARHGAP10	0.025	0.01	-10000	0	-0.11	1	1
GGA3	0.04	0.008	-10000	0	0	21	21
ARF1/GTP/Membrin	0.023	0.044	-10000	0	-0.22	14	14
AP2A1	0.039	0.01	-10000	0	0	32	32
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.012	0.032	-10000	0	-0.17	11	11
ARF1/GDP/Membrin	0.029	0.051	-10000	0	-0.25	15	15
Arfaptin 2/Rac/GDP	0.05	0.018	-10000	0	-0.11	1	1
CYTH2	-0.003	0.003	0.013	5	-0.02	1	6
ARF1/GTP/GGA3	0.048	0.02	-10000	0	-0.12	2	2
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.029	0.009	-10000	0	-0.12	1	1
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.005	0.055	-10000	0	-0.3	7	7
PLD2	0.008	0.014	0.079	15	-10000	0	15
ARF-GAP1/v-SNARE	-0.009	0.003	0	56	-10000	0	56
PIP5K1A	0.009	0.014	0.079	15	-10000	0	15
ARF1/GTP/Membrin/GBF1/p115	0.017	0.026	-10000	0	-0.074	22	22
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.008	0.014	0.079	15	-10000	0	15
KDEL Receptor/Ligand/ARF-GAP1	-0.009	0.003	0	56	-10000	0	56
GOSR2	0.013	0.036	-10000	0	-0.31	6	6
USO1	0.003	0.007	0.04	17	-0.029	1	18
GBF1	0.005	0.066	-10000	0	-0.35	18	18
ARF1/GTP/Arfaptin 2	0.05	0.019	-10000	0	-0.12	1	1
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.038	0.063	-10000	0	-0.12	45	45

×

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

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
MAP4K1	0.027	0.078	0.3	10	-0.29	1	11
CRKL	0.018	0.064	0.25	2	-0.34	2	4
HRAS	0.028	0.076	0.24	2	-0.29	5	7
mol:PIP3	0.015	0.11	0.31	4	-0.38	15	19
SPRED1	0.035	0.014	-10000	0	0	78	78
SPRED2	0.04	0.008	-10000	0	0	22	22
GAB1	0.018	0.054	-10000	0	-0.31	1	1
FOXO3	0.02	0.093	-10000	0	-0.42	11	11
AKT1	0.021	0.098	-10000	0	-0.45	11	11
BAD	0.016	0.094	-10000	0	-0.42	11	11
megakaryocyte differentiation	0.021	0.057	0.24	1	-0.3	1	2
GSK3B	0.02	0.097	0.28	5	-0.41	11	16
RAF1	0.023	0.073	0.25	7	-0.27	3	10
SHC1	0.039	0.008	-10000	0	0	23	23
STAT3	0.017	0.06	-10000	0	-0.44	2	2
STAT1	0.027	0.11	-10000	0	-0.92	3	3
HRAS/SPRED1	0.034	0.082	0.26	3	-0.31	3	6
cell proliferation	0.017	0.062	0.25	2	-0.43	2	4
PIK3CA	0.029	0.019	-10000	0	0	166	166
TEC	0.033	0.017	-10000	0	0	114	114
RPS6KB1	0.022	0.094	-10000	0	-0.38	7	7
HRAS/SPRED2	0.039	0.082	0.25	3	-0.27	4	7
LYN/TEC/p62DOK	0.038	0.095	-10000	0	-0.36	4	4
MAPK3	0.016	0.063	0.23	6	-0.26	3	9
STAP1	0.02	0.059	-10000	0	-0.43	2	2
GRAP2	0.037	0.013	-10000	0	0	56	56
JAK2	0.026	0.11	-10000	0	-0.76	3	3
STAT1 (dimer)	0.029	0.11	-10000	0	-0.9	3	3
mol:Gleevec	-0.002	0.003	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	0.058	0.089	-10000	0	-0.38	3	3
actin filament polymerization	0.02	0.06	-10000	0	-0.42	2	2
LYN	0.035	0.015	-10000	0	0	83	83
STAP1/STAT5A (dimer)	0.017	0.094	-10000	0	-0.55	4	4
PIK3R1	0.034	0.016	-10000	0	0	99	99
CBL/CRKL/GRB2	0.05	0.084	0.29	1	-0.36	2	3
PI3K	0.023	0.099	-10000	0	-0.33	10	10
PTEN	0.038	0.01	-10000	0	0	36	36
SCF/KIT/EPO/EPOR	0.056	0.13	-10000	0	-1.3	2	2
MAPK8	0.016	0.063	0.25	2	-0.44	2	4
STAT3 (dimer)	0.017	0.059	-10000	0	-0.43	2	2
positive regulation of transcription	0.015	0.057	0.21	6	-0.24	2	8
mol:GDP	0.037	0.082	-10000	0	-0.34	3	3
PIK3C2B	0.016	0.062	-10000	0	-0.44	2	2
CBL/CRKL	0.036	0.077	0.28	1	-0.36	2	3
FER	0.018	0.06	-10000	0	-0.44	2	2
SH2B3	0.02	0.059	-10000	0	-0.43	2	2
PDPK1	0.014	0.1	0.3	5	-0.33	15	20
SNAI2	0.021	0.067	0.24	2	-0.5	2	4
positive regulation of cell proliferation	0.019	0.11	-10000	0	-0.74	3	3
KITLG	0.043	0.014	-10000	0	-0.042	3	3
cell motility	0.019	0.11	-10000	0	-0.74	3	3
PTPN6	0.034	0.015	-10000	0	-0.005	67	67
EPOR	0.006	0.17	-10000	0	-0.99	2	2
STAT5A (dimer)	0.021	0.1	-10000	0	-0.56	4	4
SOCS1	0.037	0.012	-10000	0	0	51	51
cell migration	-0.017	0.058	0.43	2	-10000	0	2
SOS1	0.037	0.012	-10000	0	0	51	51
EPO	0.043	0.01	-10000	0	-0.036	3	3
VAV1	0.036	0.014	-10000	0	0	69	69
GRB10	0.017	0.061	-10000	0	-0.44	2	2
PTPN11	0.037	0.011	-10000	0	-0.004	33	33
SCF/KIT	0.024	0.064	-10000	0	-0.45	2	2
GO:0007205	-0.002	0.004	-10000	0	-10000	0	0
MAP2K1	0.014	0.064	0.24	6	-0.24	2	8
CBL	0.04	0.008	-10000	0	0	20	20
KIT	0.015	0.16	-10000	0	-0.73	5	5
MAP2K2	0.014	0.061	0.24	6	-0.24	2	8
SHC/Grb2/SOS1	0.063	0.09	-10000	0	-0.4	2	2
STAT5A	0.024	0.097	-10000	0	-0.58	4	4
GRB2	0.04	0.008	-10000	0	0	21	21
response to radiation	0.025	0.07	0.24	3	-0.49	2	5
SHC/GRAP2	0.052	0.023	-10000	0	-0.13	1	1
PTPRO	0.019	0.055	0.24	1	-0.3	1	2
SH2B2	0.02	0.059	-10000	0	-0.43	2	2
DOK1	0.04	0.008	-10000	0	0	22	22
MATK	0.016	0.059	-10000	0	-0.44	2	2
CREBBP	0.058	0.029	-10000	0	-0.14	3	3
BCL2	-0.013	0.21	-10000	0	-0.67	22	22

×

Glypican 2 network

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
MDK	0.039	0.008	-9999	0	23	23
GPC2	0.04	0.006	-9999	0	13	13
GPC2/Midkine	0.054	0.032	-9999	-0.13	14	14
neuron projection morphogenesis	0.054	0.032	-9999	-0.13	14	14

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.04	0.007	-10000	0	0	15	15
GNAT1/GTP	0.03	0.005	-10000	0	-10000	0	0
Metarhodopsin II/Arrestin	0.052	0.013	-10000	0	-10000	0	0
PDE6G/GNAT1/GTP	0.049	0.02	-10000	0	-0.11	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.04	0.006	-10000	0	0	13	13
GRK1	0	0	-10000	0	-10000	0	0
CNG Channel	0.066	0.037	-10000	0	-0.11	2	2
mol:Na +	0.068	0.041	-10000	0	-0.11	1	1
mol:ADP	0	0	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.067	0.034	-10000	0	-0.12	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.084	0.049	-10000	0	-0.11	1	1
CNGB1	0.038	0.01	-10000	0	0	38	38
RDH5	0.036	0.013	-10000	0	0	65	65
SAG	0.04	0.006	-10000	0	0	12	12
mol:Ca2+	-0.017	0.081	0.32	19	-10000	0	19
Na + (4 Units)	0.056	0.037	-10000	0	-0.11	1	1
RGS9	0.038	0.01	-10000	0	0	37	37
GNB1/GNGT1	0.054	0.024	-10000	0	-0.13	4	4
GNAT1/GDP	0.079	0.038	-10000	0	-0.1	1	1
GUCY2D	0.038	0.011	-10000	0	0	42	42
GNGT1	0.039	0.009	-10000	0	0	26	26
GUCY2F	0.041	0.002	-10000	0	0	1	1
GNB5	0.039	0.008	-10000	0	0	23	23
mol:GMP (4 units)	0.035	0.023	0.16	7	-0.1	2	9
mol:11-cis-retinal	0.036	0.013	-10000	0	0	65	65
mol:cGMP	0.075	0.034	0.2	3	-0.11	1	4
GNB1	0.039	0.01	-10000	0	0	33	33
Rhodopsin	0.05	0.03	-10000	0	-0.13	7	7
SLC24A1	0.04	0.007	-10000	0	0	15	15
CNGA1	0.04	0.008	-10000	0	0	20	20
Metarhodopsin II	0.025	0.005	-10000	0	-10000	0	0
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.09	0.038	-10000	0	-0.11	1	1
RGS9BP	0.037	0.013	-10000	0	0	56	56
Metarhodopsin II/Transducin	0.023	0.02	-10000	0	-0.14	6	6
GCAP Family/Ca ++	0.072	0.024	-10000	0	-0.1	1	1
PDE6A/B	0.055	0.019	-10000	0	-10000	0	0
mol:Pi	0.066	0.033	-10000	0	-0.12	1	1
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.07	0.029	-10000	0	-0.1	4	4
PDE6B	0.038	0.011	-10000	0	0	45	45
PDE6A	0.04	0.007	-10000	0	0	15	15
PDE6G	0.037	0.012	-10000	0	0	55	55
RHO	0.04	0.008	-10000	0	0	20	20
PDE6	0.09	0.056	-10000	0	-0.15	2	2
GUCA1A	0.039	0.008	-10000	0	0	24	24
GC2/GCAP Family	0.097	0.031	-10000	0	-0.11	1	1
GUCA1C	0.039	0.009	-10000	0	0	27	27
GUCA1B	0.04	0.008	-10000	0	0	21	21

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.062	0.027	-10000	0	-0.096	1	1
RGS9BP	0.037	0.013	-10000	0	0	56	56
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0	0	-10000	0	-10000	0	0
mol:Na +	0.05	0.016	-10000	0	-10000	0	0
mol:ADP	-0.01	0.003	-10000	0	-10000	0	0
GNAT2	0.041	0.004	-10000	0	0	6	6
RGS9-1/Gbeta5/R9AP	0.067	0.034	-10000	0	-0.12	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.05	0.017	-10000	0	-10000	0	0
GRK7	0.038	0.011	-10000	0	0	40	40
CNGB3	0.038	0.012	-10000	0	0	49	49
Cone Metarhodopsin II/X-Arrestin	0.03	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.004	0.055	0.19	40	-10000	0	40
Cone PDE6	0.089	0.055	-10000	0	-0.11	1	1
Cone Metarhodopsin II	0.024	0.007	-10000	0	-10000	0	0
Na + (4 Units)	0.067	0.028	-10000	0	-10000	0	0
GNAT2/GDP	0.08	0.037	-10000	0	-0.1	1	1
GNB5	0.039	0.008	-10000	0	0	23	23
mol:GMP (4 units)	-0.003	0.058	0.19	45	-10000	0	45
Cone Transducin	0.067	0.029	-10000	0	-0.1	1	1
SLC24A2	0.039	0.01	-10000	0	0	33	33
GNB3/GNGT2	0.052	0.022	-10000	0	-0.13	1	1
GNB3	0.037	0.012	-10000	0	0	55	55
GNAT2/GTP	0.03	0.003	-10000	0	-10000	0	0
CNGA3	0.041	0.004	-10000	0	0	4	4
ARR3	0.041	0.002	-10000	0	0	1	1
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.05	0.016	-10000	0	-10000	0	0
mol:Pi	0.066	0.033	-10000	0	-0.12	1	1
Cone CNG Channel	0.081	0.043	-10000	0	-10000	0	0
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.039	0.01	-10000	0	0	33	33
RGS9	0.038	0.01	-10000	0	0	37	37
PDE6C	0.04	0.007	-10000	0	0	18	18
GNGT2	0.039	0.008	-10000	0	0	23	23
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.037	0.012	-10000	0	0	50	50