PARADIGM pathway analysis of mRNA expression data - Glioblastoma Multiforme (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
FOXM1 transcription factor network	278
Glypican 2 network	224
RXR and RAR heterodimerization with other nuclear receptor	167
Endothelins	165
HIF-1-alpha transcription factor network	143
TCGA08_retinoblastoma	141
Osteopontin-mediated events	134
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	129
Thromboxane A2 receptor signaling	127
Syndecan-1-mediated signaling events	119

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
FOXM1 transcription factor network	0.5265	278	14184	51	-0.047	0.88	1000	-1000	-0.17	-1000
Glypican 2 network	0.4242	224	897	4	-0.006	0	1000	-1000	-0.013	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.3163	167	8699	52	-0.027	0.15	1000	-1000	-0.03	-1000
Endothelins	0.3125	165	15887	96	-0.42	0.17	1000	-1000	-0.037	-1000
HIF-1-alpha transcription factor network	0.2708	143	10935	76	-0.019	0.36	1000	-1000	-0.067	-1000
TCGA08_retinoblastoma	0.2670	141	1129	8	-0.019	0.008	1000	-1000	-0.015	-1000
Osteopontin-mediated events	0.2538	134	5121	38	-0.014	0.11	1000	-1000	-0.026	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.2443	129	8836	68	-0.44	0.32	1000	-1000	-0.065	-1000
Thromboxane A2 receptor signaling	0.2405	127	13380	105	-0.1	0.2	1000	-1000	-0.037	-1000
Syndecan-1-mediated signaling events	0.2254	119	4075	34	-0.017	0.085	1000	-1000	-0.02	-1000
LPA receptor mediated events	0.2197	116	11914	102	-0.03	0.15	1000	-1000	-0.042	-1000
Ras signaling in the CD4+ TCR pathway	0.2083	110	1885	17	-0.008	0.041	1000	-1000	-0.019	-1000
FoxO family signaling	0.2064	109	6991	64	-0.068	0.24	1000	-1000	-0.051	-1000
Effects of Botulinum toxin	0.1970	104	2711	26	-0.021	0	1000	-1000	-0.018	-1000
PLK2 and PLK4 events	0.1951	103	310	3	-0.014	-0.012	1000	-1000	-0.015	-1000
EGFR-dependent Endothelin signaling events	0.1818	96	2029	21	-0.014	0.025	1000	-1000	-0.02	-1000
HIF-2-alpha transcription factor network	0.1780	94	4084	43	-0.034	0.18	1000	-1000	-0.033	-1000
PDGFR-alpha signaling pathway	0.1572	83	3668	44	-0.02	0.051	1000	-1000	-0.023	-1000
Nongenotropic Androgen signaling	0.1534	81	4221	52	-0.13	0.046	1000	-1000	-0.021	-1000
BARD1 signaling events	0.1439	76	4355	57	-0.02	0.062	1000	-1000	-0.021	-1000
Noncanonical Wnt signaling pathway	0.1345	71	1856	26	-0.014	0.013	1000	-1000	-0.026	-1000
PLK1 signaling events	0.1345	71	6087	85	-0.014	0.059	1000	-1000	-0.017	-1000
IL2 signaling events mediated by PI3K	0.1307	69	4057	58	-0.014	0.066	1000	-1000	-0.036	-1000
Reelin signaling pathway	0.1231	65	3680	56	-0.051	0	1000	-1000	-0.025	-1000
Regulation of nuclear SMAD2/3 signaling	0.1212	64	8763	136	-0.13	0.13	1000	-1000	-0.023	-1000
IL6-mediated signaling events	0.1212	64	4860	75	-0.031	0.26	1000	-1000	-0.06	-1000
Syndecan-4-mediated signaling events	0.1136	60	4053	67	-0.017	0.023	1000	-1000	-0.019	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1117	59	5223	88	-0.047	0.18	1000	-1000	-0.048	-1000
S1P5 pathway	0.1080	57	978	17	-0.062	0.061	1000	-1000	-0.014	-1000
Plasma membrane estrogen receptor signaling	0.1080	57	4916	86	-0.47	0.076	1000	-1000	-0.025	-1000
PDGFR-beta signaling pathway	0.1004	53	5162	97	-0.03	0.077	1000	-1000	-0.028	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0985	52	1960	37	-0.023	0.055	1000	-1000	-0.02	-1000
IFN-gamma pathway	0.0947	50	3467	68	-0.1	0.02	1000	-1000	-0.033	-1000
Class I PI3K signaling events	0.0947	50	3682	73	-0.02	0.027	1000	-1000	-0.017	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0909	48	2618	54	-0.023	0	1000	-1000	-0.021	-1000
IL23-mediated signaling events	0.0909	48	2905	60	-0.02	0.11	1000	-1000	-0.11	-1000
Integrins in angiogenesis	0.0890	47	4019	84	-0.027	0.041	1000	-1000	-0.025	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0871	46	3593	78	-0.087	0.039	1000	-1000	-0.041	-1000
Aurora B signaling	0.0871	46	3088	67	-0.015	0.006	1000	-1000	-0.019	-1000
p75(NTR)-mediated signaling	0.0833	44	5512	125	-0.035	0.009	1000	-1000	-0.026	-1000
Canonical Wnt signaling pathway	0.0833	44	2274	51	-0.088	0.09	1000	-1000	-0.025	-1000
Circadian rhythm pathway	0.0814	43	957	22	-0.017	0.048	1000	-1000	-0.036	-1000
Signaling events mediated by HDAC Class I	0.0795	42	4462	104	-0.018	0.021	1000	-1000	-0.02	-1000
TCGA08_rtk_signaling	0.0795	42	1111	26	-0.014	0.024	1000	-1000	-0.018	-1000
Regulation of Telomerase	0.0795	42	4347	102	-0.026	0.07	1000	-1000	-0.051	-1000
Wnt signaling	0.0777	41	288	7	-0.014	-0.006	1000	-1000	-0.014	-1000
S1P4 pathway	0.0758	40	1008	25	-0.062	0	1000	-1000	-0.015	-1000
Presenilin action in Notch and Wnt signaling	0.0701	37	2315	61	-0.043	0.084	1000	-1000	-0.022	-1000
p38 MAPK signaling pathway	0.0701	37	1640	44	-0.019	0.003	1000	-1000	-0.018	-1000
Glypican 1 network	0.0682	36	1770	48	-0.02	0.014	1000	-1000	-0.017	-1000
BCR signaling pathway	0.0644	34	3389	99	-0.025	0.034	1000	-1000	-0.025	-1000
Arf6 downstream pathway	0.0625	33	1439	43	-0.017	0.022	1000	-1000	-0.019	-1000
amb2 Integrin signaling	0.0625	33	2772	82	-0.017	0.028	1000	-1000	-0.027	-1000
E-cadherin signaling in the nascent adherens junction	0.0625	33	2521	76	-0.028	0.022	1000	-1000	-0.027	-1000
Fc-epsilon receptor I signaling in mast cells	0.0606	32	3194	97	-0.02	0.028	1000	-1000	-0.039	-1000
IL12-mediated signaling events	0.0587	31	2720	87	-0.09	0.062	1000	-1000	-0.095	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0568	30	864	28	-0.017	0	1000	-1000	-0.015	-1000
IL1-mediated signaling events	0.0549	29	1817	62	-0.036	0.009	1000	-1000	-0.026	-1000
Insulin-mediated glucose transport	0.0530	28	916	32	-0.048	0	1000	-1000	-0.015	-1000
FAS signaling pathway (CD95)	0.0530	28	1327	47	-0.019	0.032	1000	-1000	-0.019	-1000
VEGFR1 specific signals	0.0511	27	1527	56	-0.029	0	1000	-1000	-0.023	-1000
Aurora A signaling	0.0492	26	1596	60	-0.021	0.027	1000	-1000	-0.017	-1000
Visual signal transduction: Cones	0.0473	25	955	38	-0.022	0.022	1000	-1000	-0.02	-1000
Ceramide signaling pathway	0.0473	25	1952	76	-0.022	0.017	1000	-1000	-0.018	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0473	25	1919	74	-0.18	0.021	1000	-1000	-0.032	-1000
E-cadherin signaling in keratinocytes	0.0473	25	1082	43	-0.021	0.018	1000	-1000	-0.018	-1000
ErbB2/ErbB3 signaling events	0.0455	24	1601	65	-0.027	0.052	1000	-1000	-0.043	-1000
IL4-mediated signaling events	0.0455	24	2209	91	-0.079	0.12	1000	-1000	-0.2	-1000
Ephrin B reverse signaling	0.0455	24	1190	48	-0.017	0.013	1000	-1000	-0.02	-1000
S1P1 pathway	0.0455	24	878	36	-0.066	0.045	1000	-1000	-0.026	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0436	23	532	23	-0.022	-0.002	1000	-1000	-0.017	-1000
Signaling mediated by p38-alpha and p38-beta	0.0436	23	1047	44	-0.02	0.001	1000	-1000	-0.018	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0436	23	1078	45	-0.034	0.008	1000	-1000	-0.027	-1000
Regulation of p38-alpha and p38-beta	0.0436	23	1246	54	-0.029	0	1000	-1000	-0.02	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0436	23	2789	120	-0.062	0.059	1000	-1000	-0.029	-1000
Syndecan-3-mediated signaling events	0.0398	21	762	35	-0.025	0	1000	-1000	-0.021	-1000
Arf6 signaling events	0.0379	20	1265	62	-0.024	0.005	1000	-1000	-0.019	-1000
TRAIL signaling pathway	0.0379	20	970	48	-0.024	0.002	1000	-1000	-0.021	-1000
Caspase cascade in apoptosis	0.0322	17	1298	74	-0.019	0.014	1000	-1000	-0.021	-1000
Syndecan-2-mediated signaling events	0.0322	17	1220	69	-0.024	0	1000	-1000	-0.02	-1000
TCGA08_p53	0.0322	17	120	7	-0.014	0.002	1000	-1000	-0.014	-1000
Paxillin-dependent events mediated by a4b1	0.0322	17	617	36	-0.029	0.027	1000	-1000	-0.022	-1000
IL2 signaling events mediated by STAT5	0.0322	17	390	22	-0.02	0.008	1000	-1000	-0.026	-1000
Signaling events mediated by PRL	0.0322	17	582	34	-0.018	0.011	1000	-1000	-0.02	-1000
BMP receptor signaling	0.0303	16	1351	81	-0.027	0.008	1000	-1000	-0.026	-1000
Glucocorticoid receptor regulatory network	0.0303	16	1901	114	-0.087	0.1	1000	-1000	-0.05	-1000
TCR signaling in naïve CD8+ T cells	0.0303	16	1550	93	-0.061	0.003	1000	-1000	-0.026	-1000
EPHB forward signaling	0.0303	16	1404	85	-0.038	0.033	1000	-1000	-0.027	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0303	16	2051	125	-0.024	0.037	1000	-1000	-0.033	-1000
Signaling events mediated by PTP1B	0.0284	15	1179	76	-0.02	0.038	1000	-1000	-0.029	-1000
ceramide signaling pathway	0.0284	15	773	49	-0.017	0.016	1000	-1000	-0.017	-1000
Retinoic acid receptors-mediated signaling	0.0284	15	889	58	-0.03	0.012	1000	-1000	-0.031	-1000
S1P3 pathway	0.0284	15	648	42	-0.065	0.001	1000	-1000	-0.023	-1000
Canonical NF-kappaB pathway	0.0246	13	536	39	-0.029	0	1000	-1000	-0.024	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0227	12	429	34	-0.022	0	1000	-1000	-0.016	-1000
Signaling events mediated by the Hedgehog family	0.0227	12	664	52	-0.025	0.016	1000	-1000	-0.021	-1000
Aurora C signaling	0.0227	12	87	7	-0.017	0	1000	-1000	-0.015	-1000
Signaling mediated by p38-gamma and p38-delta	0.0227	12	192	15	-0.034	0	1000	-1000	-0.017	-1000
Atypical NF-kappaB pathway	0.0227	12	379	31	-0.02	0	1000	-1000	-0.018	-1000
Cellular roles of Anthrax toxin	0.0208	11	433	39	-0.017	0.007	1000	-1000	-0.014	-1000
Nectin adhesion pathway	0.0208	11	722	63	-0.031	0.01	1000	-1000	-0.03	-1000
Calcium signaling in the CD4+ TCR pathway	0.0208	11	365	31	-0.059	0	1000	-1000	-0.028	-1000
Arf6 trafficking events	0.0208	11	801	71	-0.016	0.011	1000	-1000	-0.015	-1000
Hedgehog signaling events mediated by Gli proteins	0.0189	10	698	65	-0.042	0.008	1000	-1000	-0.031	-1000
EPO signaling pathway	0.0189	10	565	55	-0.033	0	1000	-1000	-0.02	-1000
Signaling events mediated by HDAC Class III	0.0189	10	439	40	-0.022	0.021	1000	-1000	-0.018	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0189	10	908	83	-0.068	0.066	1000	-1000	-0.022	-1000
IGF1 pathway	0.0189	10	626	57	-0.031	0.024	1000	-1000	-0.021	-1000
E-cadherin signaling events	0.0189	10	51	5	-0.02	-0.014	1000	-1000	-0.017	-1000
JNK signaling in the CD4+ TCR pathway	0.0170	9	161	17	-0.022	0.001	1000	-1000	-0.02	-1000
Class I PI3K signaling events mediated by Akt	0.0133	7	510	68	-0.043	0.03	1000	-1000	-0.02	-1000
Signaling events mediated by HDAC Class II	0.0114	6	500	75	-0.023	0.013	1000	-1000	-0.021	-1000
ErbB4 signaling events	0.0114	6	477	69	-0.024	0.016	1000	-1000	-0.029	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0114	6	557	85	-0.02	0.011	1000	-1000	-0.028	-1000
Signaling events regulated by Ret tyrosine kinase	0.0114	6	561	82	-0.029	0	1000	-1000	-0.023	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0114	6	225	33	-0.022	0	1000	-1000	-0.019	-1000
Regulation of Androgen receptor activity	0.0114	6	421	70	-0.033	0.002	1000	-1000	-0.031	-1000
FOXA2 and FOXA3 transcription factor networks	0.0095	5	230	46	-0.028	0	1000	-1000	-0.083	-1000
mTOR signaling pathway	0.0095	5	304	53	-0.022	0.029	1000	-1000	-0.024	-1000
IL27-mediated signaling events	0.0095	5	300	51	-0.043	0.009	1000	-1000	-0.04	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0076	4	110	27	-0.023	0	1000	-1000	-0.019	-1000
a4b1 and a4b7 Integrin signaling	0.0057	3	17	5	-0.017	-0.014	1000	-1000	-0.016	-1000
Insulin Pathway	0.0057	3	278	74	-0.032	0.014	1000	-1000	-0.023	-1000
LPA4-mediated signaling events	0.0019	1	12	12	-0.014	0	1000	-1000	-0.012	-1000
Coregulation of Androgen receptor activity	0.0019	1	112	76	-0.024	0.003	1000	-1000	-0.031	-1000
Rapid glucocorticoid signaling	0.0019	1	25	20	-0.014	0.002	1000	-1000	-0.014	-1000
Visual signal transduction: Rods	0.0019	1	57	52	-0.03	0	1000	-1000	-0.022	-1000
Arf1 pathway	0.0019	1	84	54	-0.017	0.006	1000	-1000	-0.014	-1000
Alternative NF-kappaB pathway	0.0019	1	18	13	-0.027	0	1000	-1000	-0.022	-1000
Ephrin A reverse signaling	0.0000	0	0	7	-0.017	0	1000	-1000	-0.014	-1000
Class IB PI3K non-lipid kinase events	0.0000	0	0	3	-0.014	-1000	1000	-1000	-0.013	-1000
Total	NA	5362	300346	7203	-5.6	-990	131000	-131000	-3.8	-131000

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.68	0.48	1	333	-10000	0	333
PLK1	0.24	0.23	0.47	220	-10000	0	220
BIRC5	0.32	0.3	0.62	244	-10000	0	244
HSPA1B	0.68	0.48	1	334	-10000	0	334
MAP2K1	0.18	0.15	0.26	366	-10000	0	366
BRCA2	0.68	0.48	1	333	-10000	0	333
FOXM1	0.88	0.7	1.3	333	-10000	0	333
XRCC1	0.68	0.48	1	333	-10000	0	333
FOXM1B/p19	0.2	0.31	0.71	119	-10000	0	119
Cyclin D1/CDK4	0.12	0.28	0.75	72	-10000	0	72
CDC2	0.83	0.64	1.2	333	-10000	0	333
TGFA	0.62	0.43	0.9	336	-10000	0	336
SKP2	0.68	0.48	1	333	-10000	0	333
CCNE1	0.042	0.036	0.063	350	-10000	0	350
CKS1B	0.73	0.54	1.1	335	-10000	0	335
RB1	0.012	0.053	0.23	17	-10000	0	17
FOXM1C/SP1	0.38	0.42	0.85	215	-10000	0	215
AURKB	0.24	0.24	0.49	208	-10000	0	208
CENPF	0.74	0.55	1.1	336	-10000	0	336
CDK4	0.015	0.038	0.091	79	-10000	0	79
MYC	0.56	0.47	0.93	299	-10000	0	299
CHEK2	0.18	0.15	0.26	373	-10000	0	373
ONECUT1	0.65	0.45	0.94	336	-10000	0	336
CDKN2A	-0.047	0.073	-10000	0	-0.13	166	166
LAMA4	0.68	0.48	1	332	-10000	0	332
FOXM1B/HNF6	0.65	0.46	0.95	334	-10000	0	334
FOS	0.71	0.5	1	332	-10000	0	332
SP1	-0.01	0.012	0.007	137	-10000	0	137
CDC25B	0.68	0.49	1	333	-10000	0	333
response to radiation	0.15	0.12	0.2	384	-10000	0	384
CENPB	0.68	0.49	1	333	-10000	0	333
CENPA	0.72	0.53	1.1	333	-10000	0	333
NEK2	0.69	0.5	1	333	-10000	0	333
HIST1H2BA	0.68	0.48	1	334	-10000	0	334
CCNA2	0.021	0.028	0.049	217	-10000	0	217
EP300	-0.014	0	-10000	0	-10000	0	0
CCNB1/CDK1	0.81	0.61	1.2	325	-10000	0	325
CCNB2	0.79	0.57	1.1	343	-10000	0	343
CCNB1	0.84	0.64	1.2	333	-10000	0	333
ETV5	0.68	0.48	1	333	-10000	0	333
ESR1	0.68	0.48	1	333	-10000	0	333
CCND1	0.66	0.48	0.97	335	-10000	0	335
GSK3A	0.16	0.12	0.21	384	-10000	0	384
Cyclin A-E1/CDK1-2	0.12	0.11	0.19	326	-10000	0	326
CDK2	0.039	0.035	0.059	347	-10000	0	347
G2/M transition of mitotic cell cycle	0.18	0.14	0.24	373	-10000	0	373
FOXM1B/Cbp/p300	0.059	0.14	0.47	14	-10000	0	14
GAS1	0.7	0.5	1	333	-10000	0	333
MMP2	0.76	0.54	1.1	334	-10000	0	334
RB1/FOXM1C	0.45	0.42	0.82	266	-10000	0	266
CREBBP	-0.014	0	-10000	0	-10000	0	0

×

Glypican 2 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.Total.Perturbations
MDK	-0.006	0.007	0	299	-9999	299
GPC2	0	0	-9999	0	-9999	0
GPC2/Midkine	-0.004	0.004	0	299	-9999	299
neuron projection morphogenesis	-0.004	0.004	0	299	-9999	299

×

RXR and RAR heterodimerization with other nuclear receptor

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.Total.Perturbations
TGFB1	-0.003	0.01	0.17	1	-9999	1
VDR	-0.014	0	-10000	0	-9999	0
FAM120B	0	0	-10000	0	-9999	0
RXRs/LXRs/DNA/9cRA	0.12	0.083	0.17	378	-9999	378
RXRs/LXRs/DNA/Oxysterols	0.15	0.1	0.21	378	-9999	378
MED1	-0.014	0	-10000	0	-9999	0
mol:9cRA	0.027	0.018	0.039	381	-9999	381
RARs/THRs/DNA/Src-1	-0.011	0.002	-10000	0	-9999	0
RXRs/NUR77	0.076	0.066	0.12	378	-9999	378
RXRs/PPAR	0.035	0.031	0.054	381	-9999	381
NCOR2	-0.014	0	-10000	0	-9999	0
VDR/VDR/Vit D3	-0.009	0	-10000	0	-9999	0
RARs/VDR/DNA/Vit D3	-0.022	0	-10000	0	-9999	0
RARA	-0.014	0	-10000	0	-9999	0
NCOA1	-0.014	0.002	0	14	-9999	14
VDR/VDR/DNA	-0.014	0	-10000	0	-9999	0
RARs/RARs/DNA/9cRA	0.022	0.025	0.037	381	-9999	381
RARG	-0.014	0	-10000	0	-9999	0
RPS6KB1	-0.004	0.014	0.26	1	-9999	1
RARs/THRs/DNA/SMRT	-0.011	0	-10000	0	-9999	0
THRA	-0.014	0	-10000	0	-9999	0
mol:Bile acids	0	0	-10000	0	-9999	0
VDR/Vit D3/DNA	-0.009	0	-10000	0	-9999	0
RXRs/PPAR/9cRA/PGJ2/DNA	0.11	0.092	0.17	352	-9999	352
NR1H4	-0.014	0	-10000	0	-9999	0
RXRs/LXRs/DNA	0.12	0.099	0.19	380	-9999	380
NR1H2	0.029	0.028	0.046	381	-9999	381
NR1H3	0.03	0.028	0.048	379	-9999	379
RXRs/VDR/DNA/Vit D3	0.07	0.061	0.11	378	-9999	378
NR4A1	-0.014	0	-10000	0	-9999	0
mol:ATRA	0	0	-10000	0	-9999	0
RXRs/FXR/9cRA/MED1	0.049	0.037	0.072	381	-9999	381
RXRG	0.028	0.028	0.045	378	-9999	378
RXR alpha/CCPG	0.021	0.019	0.033	381	-9999	381
RXRA	0.028	0.028	0.045	381	-9999	381
RXRB	0.029	0.029	0.047	381	-9999	381
THRB	-0.014	0	-10000	0	-9999	0
PPARG	-0.014	0.001	0	5	-9999	5
PPARD	-0.014	0	-10000	0	-9999	0
TNF	0.14	0.098	0.2	379	-9999	379
mol:Oxysterols	0.026	0.017	0.037	381	-9999	381
cholesterol transport	0.15	0.1	0.21	378	-9999	378
PPARA	-0.014	0	-10000	0	-9999	0
mol:Vit D3	0	0	-10000	0	-9999	0
RARB	-0.014	0	-10000	0	-9999	0
RXRs/NUR77/BCL2	0.017	0.018	0.028	378	-9999	378
SREBF1	0.14	0.097	0.2	381	-9999	381
RXRs/RXRs/DNA/9cRA	0.11	0.092	0.17	352	-9999	352
ABCA1	-0.004	0.015	0.2	2	-9999	2
RARs/THRs	-0.027	0	-10000	0	-9999	0
RXRs/FXR	0.076	0.066	0.12	378	-9999	378
BCL2	-0.014	0	-10000	0	-9999	0

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.15	0.13	0.23	357	-10000	0	357
PTK2B	-0.014	0.002	0.013	4	-10000	0	4
mol:Ca2+	0.097	0.076	0.5	4	-10000	0	4
EDN1	0.08	0.077	0.13	354	-10000	0	354
EDN3	-0.014	0.001	0	4	-10000	0	4
EDN2	-0.014	0.001	0	1	-10000	0	1
HRAS/GDP	0.13	0.096	0.2	275	-0.18	2	277
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.068	0.08	0.16	192	-0.1	1	193
ADCY4	0.06	0.087	0.15	232	-10000	0	232
ADCY5	0.06	0.087	0.15	232	-10000	0	232
ADCY6	0.14	0.1	0.19	389	-10000	0	389
ADCY7	0.14	0.1	0.19	384	-10000	0	384
ADCY1	0.14	0.1	0.19	389	-10000	0	389
ADCY2	0.14	0.1	0.19	389	-10000	0	389
ADCY3	0.06	0.087	0.15	232	-10000	0	232
ADCY8	0.14	0.1	0.19	383	-10000	0	383
ADCY9	0.14	0.1	0.19	389	-10000	0	389
arachidonic acid secretion	0.13	0.13	0.33	127	-0.34	2	129
ETB receptor/Endothelin-1/Gq/GTP	0.066	0.065	0.12	264	-10000	0	264
GNAO1	-0.001	0.004	0	481	-10000	0	481
HRAS	-0.008	0.012	0.013	127	-10000	0	127
ETA receptor/Endothelin-1/G12/GTP	-0.003	0.026	0.15	10	-10000	0	10
ETA receptor/Endothelin-1/Gs/GTP	-0.003	0.025	0.14	11	-10000	0	11
mol:GTP	0.004	0.007	0.016	125	-10000	0	125
COL3A1	-0.002	0.032	0.14	14	-10000	0	14
EDNRB	0.039	0.054	0.098	236	-10000	0	236
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	0.15	0.13	0.23	361	-10000	0	361
CYSLTR1	0.13	0.13	0.22	322	-10000	0	322
SLC9A1	-0.002	0.014	0.079	11	-0.058	1	12
mol:GDP	0.13	0.099	0.21	265	-0.2	1	266
SLC9A3	0.099	0.11	0.33	6	-0.35	10	16
RAF1	0.13	0.12	0.3	130	-0.32	2	132
JUN	0.096	0.074	0.46	4	-10000	0	4
JAK2	0.15	0.13	0.23	361	-10000	0	361
mol:IP3	0.072	0.091	0.18	185	-10000	0	185
ETA receptor/Endothelin-1	-0.005	0.03	0.16	11	-10000	0	11
PLCB1	-0.007	0.013	0.018	124	-10000	0	124
PLCB2	-0.005	0.015	0.022	125	-10000	0	125
ETA receptor/Endothelin-3	0.033	0.053	0.09	225	-10000	0	225
FOS	0.14	0.16	0.4	125	-0.64	2	127
Gai/GDP	-0.42	0.16	-10000	0	-0.46	480	480
CRK	-0.014	0.002	0.013	4	-10000	0	4
mol:Ca ++	0.17	0.14	0.27	301	-10000	0	301
BCAR1	0	0	-10000	0	-10000	0	0
PRKCB1	0.004	0.024	0.15	12	-10000	0	12
GNAQ	-0.006	0.016	0.023	125	-10000	0	125
GNAZ	-0.012	0.005	0	72	-10000	0	72
GNAL	-0.014	0	-10000	0	-10000	0	0
Gs family/GDP	0.11	0.084	0.18	250	-0.19	1	251
ETA receptor/Endothelin-1/Gq/GTP	0.054	0.075	0.16	142	-10000	0	142
MAPK14	0.058	0.058	0.11	279	-0.13	1	280
TRPC6	0.098	0.076	0.5	4	-10000	0	4
GNAI2	-0.014	0.001	0	1	-10000	0	1
GNAI3	-0.012	0.005	0	65	-10000	0	65
GNAI1	-0.012	0.005	0	81	-10000	0	81
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.065	0.064	0.12	258	-10000	0	258
ETB receptor/Endothelin-2	0.029	0.044	0.077	236	-10000	0	236
ETB receptor/Endothelin-3	0.029	0.044	0.077	234	-10000	0	234
ETB receptor/Endothelin-1	0.015	0.04	0.078	129	-10000	0	129
MAPK3	0.14	0.15	0.38	125	-0.62	2	127
MAPK1	0.13	0.16	0.38	125	-0.62	2	127
Rac1/GDP	0.13	0.093	0.2	265	-0.2	1	266
cAMP biosynthetic process	0.13	0.092	0.18	374	-10000	0	374
MAPK8	0.1	0.077	0.42	5	-10000	0	5
SRC	-0.014	0.002	0.012	4	-10000	0	4
ETB receptor/Endothelin-1/Gi/GTP	0.004	0.019	0.11	14	-10000	0	14
p130Cas/CRK/Src/PYK2	0.12	0.093	0.26	93	-10000	0	93
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	0.13	0.093	0.2	264	-0.18	2	266
COL1A2	0.022	0.056	0.12	122	-10000	0	122
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.033	0.053	0.09	226	-10000	0	226
mol:DAG	0.073	0.091	0.18	185	-10000	0	185
MAP2K2	0.13	0.14	0.35	125	-0.47	2	127
MAP2K1	0.13	0.14	0.35	125	-0.47	2	127
EDNRA	0.046	0.069	0.12	232	-10000	0	232
positive regulation of muscle contraction	0.11	0.11	0.19	317	-10000	0	317
Gq family/GDP	0.015	0.03	0.13	13	-0.16	2	15
HRAS/GTP	0.12	0.1	0.2	273	-0.19	2	275
PRKCH	0.093	0.088	0.17	254	-10000	0	254
RAC1	-0.014	0	-10000	0	-10000	0	0
PRKCA	0.092	0.088	0.17	254	-10000	0	254
PRKCB	0.097	0.089	0.18	261	-0.12	1	262
PRKCE	0.092	0.087	0.17	254	-10000	0	254
PRKCD	0.093	0.089	0.17	254	-0.12	1	255
PRKCG	0.093	0.089	0.17	254	-10000	0	254
regulation of vascular smooth muscle contraction	0.14	0.17	0.41	114	-0.81	2	116
PRKCQ	0.093	0.088	0.17	254	-10000	0	254
PLA2G4A	0.13	0.13	0.33	127	-0.37	2	129
GNA14	-0.005	0.016	0.023	125	-10000	0	125
GNA15	-0.007	0.014	0.018	122	-10000	0	122
GNA12	-0.014	0.001	0	4	-10000	0	4
GNA11	-0.007	0.014	0.018	125	-10000	0	125
Rac1/GTP	-0.003	0.027	0.15	11	-10000	0	11
MMP1	0.001	0.013	0.2	1	-0.058	9	10

×

HIF-1-alpha transcription factor network

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
PKM2	0.23	0.37	0.64	213	-10000	0	213
HDAC7	-0.002	0.003	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.002	0.13	0.36	31	-10000	0	31
SMAD4	-0.012	0.01	0.072	4	-10000	0	4
ID2	0.23	0.37	0.64	213	-10000	0	213
AP1	-0.013	0.009	0.096	1	-10000	0	1
ABCG2	0.23	0.37	0.66	200	-10000	0	200
HIF1A	0.059	0.11	0.2	165	-10000	0	165
TFF3	0.22	0.36	0.64	211	-10000	0	211
GATA2	-0.013	0.013	0.082	9	-10000	0	9
AKT1	0.13	0.14	0.25	274	-10000	0	274
response to hypoxia	0.098	0.13	0.23	227	-10000	0	227
MCL1	0.22	0.37	0.66	199	-10000	0	199
NDRG1	0.22	0.36	0.66	198	-10000	0	198
SERPINE1	0.065	0.25	0.53	96	-10000	0	96
FECH	0.23	0.37	0.64	213	-10000	0	213
FURIN	0.23	0.37	0.66	200	-10000	0	200
NCOA2	-0.015	0.001	-10000	0	-10000	0	0
EP300	0.27	0.22	0.43	320	-10000	0	320
HMOX1	-0.006	0.15	0.45	31	-10000	0	31
BHLHE40	0.21	0.36	0.63	206	-10000	0	206
BHLHE41	0.21	0.36	0.63	206	-10000	0	206
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.019	0.082	0.2	70	-10000	0	70
ENG	0.18	0.15	0.29	315	-10000	0	315
JUN	-0.014	0.009	0.053	9	-10000	0	9
RORA	0.23	0.37	0.64	213	-10000	0	213
ABCB1	-0.012	0.031	-10000	0	-10000	0	0
TFRC	0.23	0.37	0.64	213	-10000	0	213
CXCR4	0.032	0.22	0.58	54	-10000	0	54
TF	0.23	0.36	0.64	211	-10000	0	211
CITED2	0.22	0.36	0.63	206	-10000	0	206
HIF1A/ARNT	0.031	0.2	0.51	53	-10000	0	53
LDHA	-0.011	0.053	-10000	0	-0.56	4	4
ETS1	0.23	0.37	0.64	213	-10000	0	213
PGK1	0.23	0.37	0.64	213	-10000	0	213
NOS2	0.21	0.36	0.63	206	-10000	0	206
ITGB2	0.041	0.23	0.54	72	-10000	0	72
ALDOA	0.23	0.37	0.66	200	-10000	0	200
Cbp/p300/CITED2	0.17	0.33	0.61	170	-10000	0	170
FOS	-0.011	0.007	0.046	1	-10000	0	1
HK2	0.23	0.37	0.64	213	-10000	0	213
SP1	-0.019	0.015	0.092	9	-10000	0	9
GCK	0.34	0.27	0.59	243	-10000	0	243
HK1	0.23	0.36	0.66	200	-10000	0	200
NPM1	0.22	0.37	0.66	199	-10000	0	199
EGLN1	0.23	0.37	0.64	213	-10000	0	213
CREB1	-0.017	0.007	-10000	0	-0.087	5	5
PGM1	0.23	0.37	0.66	200	-10000	0	200
SMAD3	-0.016	0.009	0.075	5	-10000	0	5
EDN1	0.23	0.19	0.41	219	-10000	0	219
IGFBP1	0.22	0.36	0.64	208	-10000	0	208
VEGFA	0.066	0.21	0.47	97	-10000	0	97
HIF1A/JAB1	0.004	0.036	0.096	38	-10000	0	38
CP	0.098	0.29	0.58	117	-10000	0	117
CXCL12	0.21	0.36	0.66	191	-10000	0	191
COPS5	-0.015	0	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.016	0.009	-10000	0	-10000	0	0
BNIP3	0.23	0.37	0.66	200	-10000	0	200
EGLN3	0.22	0.36	0.66	198	-10000	0	198
CA9	0.2	0.35	0.63	194	-10000	0	194
TERT	0.23	0.37	0.64	213	-10000	0	213
ENO1	0.23	0.37	0.64	213	-10000	0	213
PFKL	0.23	0.37	0.64	213	-10000	0	213
NCOA1	-0.015	0.002	-10000	0	-10000	0	0
ADM	0.021	0.2	0.52	54	-10000	0	54
ARNT	0.059	0.11	0.2	166	-10000	0	166
HNF4A	-0.015	0	-10000	0	-10000	0	0
ADFP	0.056	0.24	0.55	84	-10000	0	84
SLC2A1	0.36	0.35	0.61	318	-10000	0	318
LEP	0.23	0.37	0.64	213	-10000	0	213
HIF1A/ARNT/Cbp/p300	-0.001	0.13	0.38	31	-10000	0	31
EPO	0.34	0.29	0.56	304	-10000	0	304
CREBBP	0.27	0.22	0.43	318	-10000	0	318
HIF1A/ARNT/Cbp/p300/HDAC7	-0.008	0.12	0.36	18	-10000	0	18
PFKFB3	0.23	0.37	0.64	213	-10000	0	213
NT5E	0.19	0.35	0.63	188	-10000	0	188

×

TCGA08_retinoblastoma

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
CDKN2B	0.001	0.014	0.012	332	-0.033	3	335
CDKN2C	-0.001	0.01	0.014	95	-0.036	11	106
CDKN2A	-0.019	0.021	0.014	95	-0.038	262	357
CCND2	-0.007	0.021	-10000	0	-0.063	65	65
RB1	0.008	0.026	0.074	68	-10000	0	68
CDK4	-0.008	0.025	-10000	0	-0.076	65	65
CDK6	-0.007	0.023	-10000	0	-0.069	65	65
G1/S progression	-0.004	0.029	-10000	0	-0.073	68	68

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.056	0.089	0.14	227	-9999	227
NF kappa B1 p50/RelA/I kappa B alpha	0.059	0.1	0.21	129	-9999	129
alphaV/beta3 Integrin/Osteopontin/Src	0.005	0.028	0.04	164	-9999	164
AP1	0.016	0.092	0.26	54	-9999	54
ILK	0.062	0.085	0.15	222	-9999	222
bone resorption	0	0.022	0.1	13	-9999	13
PTK2B	-0.014	0	-10000	0	-9999	0
PYK2/p130Cas	0.004	0.037	0.074	65	-9999	65
ITGAV	0.005	0.024	0.031	186	-9999	186
mol:GTP	0	0	-10000	0	-9999	0
CD44/Rho Family GTPase/ROCK2	-0.004	0.007	0	415	-9999	415
alphaV/beta3 Integrin/Osteopontin	0.011	0.044	0.069	164	-9999	164
MAP3K1	0.062	0.085	0.15	222	-9999	222
JUN	0.004	0.018	0.02	290	-9999	290
MAPK3	0.066	0.11	0.2	178	-9999	178
MAPK1	0.067	0.11	0.2	178	-9999	178
Rac1/GDP	-0.009	0	-10000	0	-9999	0
NFKB1	-0.014	0.001	0	4	-9999	4
MAPK8	0.074	0.099	0.16	242	-9999	242
ITGB3	0.006	0.024	0.031	196	-9999	196
NFKBIA	0.066	0.11	0.24	131	-9999	131
FOS	0.002	0.015	0.019	202	-9999	202
CD44	-0.003	0.006	0	415	-9999	415
CHUK	-0.014	0.001	0	1	-9999	1
PLAU	0.11	0.17	0.39	124	-9999	124
NF kappa B1 p50/RelA	0.053	0.11	0.24	119	-9999	119
BCAR1	0	0	-10000	0	-9999	0
RELA	-0.014	0	-10000	0	-9999	0
alphaV beta3 Integrin	0.014	0.038	0.047	280	-9999	280
mol:GDP	0	0	-10000	0	-9999	0
SYK	0.04	0.072	0.12	195	-9999	195
VAV3	0.03	0.067	0.11	178	-9999	178
MAP3K14	0.062	0.096	0.16	232	-9999	232
ROCK2	-0.014	0	-10000	0	-9999	0
SPP1	0.001	0.017	0.03	72	-9999	72
RAC1	-0.014	0	-10000	0	-9999	0
Rac1/GTP	0.026	0.06	0.1	176	-9999	176
MMP2	0.007	0.062	0.17	47	-9999	47

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.019	0.008	0.059	6	-10000	0	6
NFATC2	-0.15	0.13	0.2	2	-0.28	212	214
NFATC3	-0.15	0.1	0.17	3	-0.23	277	280
CD40LG	-0.26	0.3	0.36	34	-0.55	230	264
ITCH	-0.023	0.031	0.15	16	-10000	0	16
CBLB	-0.023	0.031	0.15	16	-10000	0	16
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.2	0.17	-10000	0	-0.38	228	228
JUNB	-0.014	0.002	0	8	-10000	0	8
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.029	0.009	-10000	0	-10000	0	0
T cell anergy	-0.032	0.049	0.22	14	-10000	0	14
TLE4	-0.093	0.088	0.13	5	-0.18	209	214
Jun/NFAT1-c-4/p21SNFT	-0.31	0.26	0.28	1	-0.57	240	241
AP-1/NFAT1-c-4	-0.31	0.27	-10000	0	-0.59	230	230
IKZF1	-0.093	0.088	0.13	5	-0.18	215	220
T-helper 2 cell differentiation	-0.14	0.14	-10000	0	-0.45	29	29
AP-1/NFAT1	-0.071	0.077	0.17	1	-0.18	117	118
CALM1	-0.024	0.02	0.082	16	-10000	0	16
EGR2	-0.31	0.26	0.46	3	-0.57	248	251
EGR3	-0.44	0.4	0.42	2	-0.86	244	246
NFAT1/FOXP3	-0.1	0.087	0.14	5	-0.19	206	211
EGR1	-0.015	0.004	0.037	1	-10000	0	1
JUN	-0.008	0.027	0.076	24	-10000	0	24
EGR4	-0.015	0.003	0.028	2	-10000	0	2
mol:Ca2+	-0.014	0.003	-10000	0	-10000	0	0
GBP3	-0.088	0.085	0.13	4	-0.18	212	216
FOSL1	-0.014	0.002	-10000	0	-10000	0	0
NFAT1-c-4/MAF/IRF4	-0.31	0.26	0.25	2	-0.56	249	251
DGKA	-0.093	0.088	0.13	5	-0.18	211	216
CREM	-0.014	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.32	0.27	0.23	4	-0.58	249	253
CTLA4	-0.083	0.073	0.1	7	-0.16	206	213
NFAT1-c-4 (dimer)/EGR1	-0.32	0.27	0.23	5	-0.58	249	254
NFAT1-c-4 (dimer)/EGR4	-0.32	0.27	0.23	5	-0.58	249	254
FOS	-0.008	0.019	0.071	11	-10000	0	11
IFNG	-0.13	0.11	-10000	0	-0.33	30	30
T cell activation	-0.15	0.17	0.37	5	-0.43	1	6
MAF	-0.014	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.3	0.25	0.55	244	-0.36	4	248
TNF	-0.3	0.26	0.28	7	-0.55	248	255
FASLG	-0.41	0.38	0.48	2	-0.79	249	251
TBX21	-0.015	0.005	0.11	1	-10000	0	1
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	-0.015	0	-10000	0	-10000	0	0
PTPN1	-0.093	0.088	0.13	5	-0.18	211	216
NFAT1-c-4/ICER1	-0.32	0.27	0.23	5	-0.58	249	254
GATA3	-0.014	0.001	-10000	0	-10000	0	0
T-helper 1 cell differentiation	-0.13	0.11	-10000	0	-0.34	25	25
IL2RA	-0.21	0.17	0.16	1	-0.38	230	231
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.096	0.082	0.14	2	-0.18	215	217
E2F1	0.055	0.052	0.093	342	-10000	0	342
PPARG	-0.014	0.001	-10000	0	-10000	0	0
SLC3A2	-0.093	0.087	0.13	4	-0.18	209	213
IRF4	-0.014	0.001	-10000	0	-10000	0	0
PTGS2	-0.28	0.27	0.27	14	-0.55	230	244
CSF2	-0.26	0.3	0.36	34	-0.55	230	264
JunB/Fra1/NFAT1-c-4	-0.31	0.26	0.23	6	-0.56	248	254
IL4	-0.14	0.15	-10000	0	-0.46	29	29
IL5	-0.26	0.3	0.36	34	-0.55	230	264
IL2	-0.15	0.17	0.37	5	-0.43	1	6
IL3	-0.066	0.049	-10000	0	-10000	0	0
RNF128	-0.027	0.008	-10000	0	-10000	0	0
NFATC1	-0.3	0.25	0.36	4	-0.55	244	248
CDK4	0.32	0.25	0.49	314	-0.37	2	316
PTPRK	-0.082	0.088	0.13	5	-0.18	185	190
IL8	-0.28	0.25	-10000	0	-0.56	215	215
POU2F1	-0.015	0	-10000	0	-10000	0	0

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.003	0.013	0.012	342	-10000	0	342
GNB1/GNG2	-0.004	0.007	-10000	0	-10000	0	0
AKT1	0.13	0.099	0.19	340	-10000	0	340
EGF	-0.014	0.001	0	2	-10000	0	2
mol:TXA2	0	0	0.005	2	-10000	0	2
FGR	-0.016	0.009	-10000	0	-10000	0	0
mol:Ca2+	0.16	0.12	0.24	353	-10000	0	353
LYN	-0.015	0.01	0.073	1	-10000	0	1
RhoA/GTP	-0.002	0.004	-10000	0	-10000	0	0
mol:PGI2	0	0	0.004	2	-10000	0	2
SYK	0.17	0.13	0.25	341	-10000	0	341
GNG2	0	0	-10000	0	-10000	0	0
ARRB2	-0.014	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.008	0.019	-10000	0	-0.16	7	7
G beta5/gamma2	-0.005	0.008	-10000	0	-10000	0	0
PRKCH	0.16	0.13	0.25	340	-10000	0	340
DNM1	-0.003	0.005	0	432	-10000	0	432
TXA2/TP beta/beta Arrestin3	0.001	0.002	-10000	0	-10000	0	0
mol:GTP	0.003	0.003	0.004	353	-10000	0	353
PTGDR	-0.014	0.002	0.013	2	-10000	0	2
G12 family/GTP	0.002	0.007	-10000	0	-10000	0	0
ADRBK1	-0.014	0.001	0.011	1	-10000	0	1
ADRBK2	-0.014	0.001	0.011	1	-10000	0	1
RhoA/GTP/ROCK1	0.005	0.013	0.014	352	-10000	0	352
mol:GDP	-0.1	0.083	-10000	0	-0.16	339	339
mol:NADP	-0.013	0.004	0.011	14	-10000	0	14
RAB11A	-0.014	0.001	0	1	-10000	0	1
PRKG1	-0.013	0.004	0.011	14	-10000	0	14
mol:IP3	0.18	0.13	0.26	339	-10000	0	339
cell morphogenesis	0.005	0.013	0.014	352	-10000	0	352
PLCB2	0.19	0.14	0.5	21	-10000	0	21
mol:cGMP	0.001	0.001	0.005	2	-10000	0	2
BLK	-0.016	0.011	0.087	2	-10000	0	2
mol:PDG2	0	0	0.004	2	-10000	0	2
HCK	-0.014	0.01	-10000	0	-10000	0	0
RHOA	-0.014	0.001	0	2	-10000	0	2
PTGIR	-0.014	0.002	0.013	2	-10000	0	2
PRKCB1	0.16	0.13	0.25	339	-10000	0	339
GNAQ	-0.014	0	-10000	0	-10000	0	0
mol:L-citrulline	-0.013	0.004	0.011	14	-10000	0	14
TXA2/TXA2-R family	0.19	0.14	0.51	21	-10000	0	21
LCK	-0.016	0.011	0.087	2	-10000	0	2
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.023	0.002	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	-0.003	0.041	-10000	0	-0.38	6	6
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.023	0.002	-10000	0	-10000	0	0
MAPK14	0.13	0.11	0.2	353	-10000	0	353
TGM2/GTP	0.19	0.14	0.28	339	-10000	0	339
MAPK11	0.13	0.11	0.2	353	-10000	0	353
ARHGEF1	0.096	0.083	0.15	353	-10000	0	353
GNAI2	-0.014	0.001	0	1	-10000	0	1
JNK cascade	0.18	0.14	0.26	339	-10000	0	339
RAB11/GDP	-0.018	0.004	-10000	0	-0.032	14	14
ICAM1	0.15	0.12	0.23	353	-10000	0	353
cAMP biosynthetic process	0.16	0.12	0.24	339	-10000	0	339
Gq family/GTP/EBP50	-0.007	0.004	0.047	2	-10000	0	2
actin cytoskeleton reorganization	0.005	0.013	0.014	352	-10000	0	352
SRC	-0.016	0.011	0.087	2	-10000	0	2
GNB5	-0.014	0.002	0.001	8	-10000	0	8
GNB1	-0.014	0.002	0	6	-10000	0	6
EGF/EGFR	0.012	0.034	0.096	38	-10000	0	38
VCAM1	0.18	0.14	0.28	353	-10000	0	353
TP beta/Gq family/GDP/G beta5/gamma2	-0.008	0.019	-10000	0	-0.16	7	7
platelet activation	0.16	0.13	0.24	341	-10000	0	341
PGI2/IP	-0.007	0.003	0.01	19	-10000	0	19
PRKACA	-0.005	0.003	0.012	15	-10000	0	15
Gq family/GDP/G beta5/gamma2	-0.005	0.008	0.056	7	-10000	0	7
TXA2/TP beta/beta Arrestin2	-0.001	0.013	-10000	0	-0.3	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.009	0.004	0.01	15	-10000	0	15
mol:DAG	0.18	0.14	0.27	339	-10000	0	339
EGFR	-0.009	0.007	0	194	-10000	0	194
TXA2/TP alpha	0.18	0.14	0.28	339	-10000	0	339
Gq family/GTP	-0.006	0.008	0.062	7	-10000	0	7
YES1	-0.014	0.012	0.087	2	-10000	0	2
GNAI2/GTP	0.004	0.02	0.018	335	-10000	0	335
PGD2/DP	-0.007	0.003	0.01	19	-10000	0	19
SLC9A3R1	-0.014	0.001	0	2	-10000	0	2
FYN	-0.015	0.012	0.087	2	-10000	0	2
mol:NO	-0.013	0.004	0.011	14	-10000	0	14
GNA15	-0.014	0.002	0	7	-10000	0	7
PGK/cGMP	0.005	0.013	0.014	353	-10000	0	353
RhoA/GDP	-0.018	0.004	-10000	0	-0.032	14	14
TP alpha/TGM2/GDP/G beta/gamma	-0.022	0.003	-10000	0	-10000	0	0
NOS3	-0.013	0.004	0.011	14	-10000	0	14
RAC1	-0.014	0	-10000	0	-10000	0	0
PRKCA	0.16	0.13	0.25	339	-10000	0	339
PRKCB	0.17	0.13	0.25	340	-10000	0	340
PRKCE	0.17	0.13	0.25	339	-10000	0	339
PRKCD	0.17	0.13	0.26	339	-10000	0	339
PRKCG	0.17	0.13	0.26	339	-10000	0	339
muscle contraction	0.18	0.14	0.28	339	-10000	0	339
PRKCZ	0.16	0.13	0.25	340	-10000	0	340
ARR3	-0.014	0	-10000	0	-10000	0	0
TXA2/TP beta	0.005	0.019	0.099	2	-10000	0	2
PRKCQ	0.17	0.13	0.25	340	-10000	0	340
MAPKKK cascade	0.18	0.14	0.26	339	-10000	0	339
SELE	0.15	0.12	0.23	353	-10000	0	353
TP beta/GNAI2/GDP/G beta/gamma	-0.023	0.003	-10000	0	-10000	0	0
ROCK1	-0.014	0	-10000	0	-10000	0	0
GNA14	-0.014	0.001	0	2	-10000	0	2
chemotaxis	0.2	0.15	0.62	16	-10000	0	16
GNA12	-0.014	0.001	0	4	-10000	0	4
GNA13	-0.014	0.001	0	2	-10000	0	2
GNA11	-0.014	0	-10000	0	-10000	0	0
Rac1/GTP	0.003	0.009	0.009	353	-10000	0	353

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.013	0.003	0	27	-9999	27
CCL5	-0.013	0.003	0	28	-9999	28
SDCBP	-0.014	0	-10000	0	-9999	0
FGFR/FGF2/Syndecan-1	0.043	0.072	0.099	256	-9999	256
mol:PI-4-5-P2	0	0	-10000	0	-9999	0
RP11-540L11.1	0	0	-10000	0	-9999	0
Syndecan-1/Laminin-5	0.035	0.065	0.099	208	-9999	208
Syndecan-1/Syntenin	0.037	0.067	0.1	218	-9999	218
MAPK3	0.003	0.026	0.11	21	-9999	21
HGF/MET	-0.017	0.003	0	12	-9999	12
TGFB1/TGF beta receptor Type II	-0.013	0.003	0	27	-9999	27
BSG	-0.014	0	-10000	0	-9999	0
keratinocyte migration	0.034	0.064	0.098	208	-9999	208
Syndecan-1/RANTES	0.03	0.059	0.091	196	-9999	196
Syndecan-1/CD147	0.006	0.03	0.084	52	-9999	52
Syndecan-1/Syntenin/PIP2	0.027	0.051	0.082	201	-9999	201
LAMA5	-0.014	0.002	0	14	-9999	14
positive regulation of cell-cell adhesion	0.026	0.049	0.079	199	-9999	199
MMP7	-0.012	0.005	0	78	-9999	78
HGF	-0.014	0.001	0	2	-9999	2
Syndecan-1/CASK	0.01	0.026	0.052	118	-9999	118
Syndecan-1/HGF/MET	0.033	0.066	0.099	210	-9999	210
regulation of cell adhesion	0.085	0.079	0.12	386	-9999	386
HPSE	-0.013	0.004	0	44	-9999	44
positive regulation of cell migration	0.043	0.072	0.099	256	-9999	256
SDC1	0.025	0.047	0.075	214	-9999	214
Syndecan-1/Collagen	0.043	0.072	0.099	256	-9999	256
PPIB	-0.004	0.006	0	373	-9999	373
MET	-0.014	0.002	0	10	-9999	10
PRKACA	-0.014	0	-10000	0	-9999	0
MMP9	-0.009	0.007	0	179	-9999	179
MAPK1	0.003	0.026	0.11	21	-9999	21
homophilic cell adhesion	0.043	0.073	0.11	218	-9999	218
MMP1	-0.013	0.004	0	43	-9999	43

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.004	0.007	0.01	51	-10000	0	51
NF kappa B1 p50/RelA/I kappa B alpha	0.029	0.05	0.11	59	-10000	0	59
AP1	0	0.022	0.078	36	-10000	0	36
mol:PIP3	-0.007	0.01	-10000	0	-10000	0	0
AKT1	0.041	0.064	0.11	247	-0.16	1	248
PTK2B	0.047	0.054	0.1	250	-10000	0	250
RHOA	0.04	0.053	0.095	247	-0.25	2	249
PIK3CB	-0.015	0.001	-10000	0	-10000	0	0
mol:Ca2+	0.016	0.031	0.061	60	-10000	0	60
MAGI3	0	0	-10000	0	-0.002	6	6
RELA	-0.014	0.001	-10000	0	-10000	0	0
apoptosis	-0.003	0.004	0	320	-10000	0	320
HRAS/GDP	-0.009	0.001	0	2	-10000	0	2
positive regulation of microtubule depolymerization	0.041	0.057	0.097	250	-10000	0	250
NF kappa B1 p50/RelA	-0.003	0.034	0.086	57	-10000	0	57
endothelial cell migration	-0.006	0.005	0	250	-10000	0	250
ADCY4	0.003	0.022	0.13	16	-10000	0	16
ADCY5	0.003	0.022	0.13	16	-10000	0	16
ADCY6	0.003	0.022	0.13	16	-10000	0	16
ADCY7	0.003	0.022	0.13	16	-10000	0	16
ADCY1	0.003	0.022	0.13	16	-10000	0	16
ADCY2	0.003	0.022	0.13	16	-10000	0	16
ADCY3	0.003	0.022	0.13	16	-10000	0	16
ADCY8	0.003	0.022	0.13	16	-10000	0	16
ADCY9	0.003	0.022	0.13	16	-10000	0	16
GSK3B	0.039	0.051	0.092	250	-10000	0	250
arachidonic acid secretion	0.003	0.021	0.12	16	-10000	0	16
GNG2	-0.001	0.001	-10000	0	-0.002	33	33
TRIP6	0.006	0.017	0.041	96	-10000	0	96
GNAO1	0.004	0.027	0.16	16	-10000	0	16
HRAS	-0.014	0.001	0	2	-10000	0	2
NFKBIA	0.027	0.045	0.073	250	-10000	0	250
GAB1	-0.014	0.001	0	4	-10000	0	4
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.016	0.16	-10000	0	-0.79	21	21
JUN	-0.013	0.002	0.008	5	-10000	0	5
LPA/LPA2/NHERF2	-0.003	0.006	0.002	303	-10000	0	303
TIAM1	-0.03	0.18	-10000	0	-0.9	21	21
PIK3R1	-0.014	0.004	0	36	-10000	0	36
mol:IP3	0.016	0.031	0.061	60	-10000	0	60
PLCB3	0.023	0.038	0.062	250	-10000	0	250
FOS	-0.01	0.006	0	127	-10000	0	127
positive regulation of mitosis	0.003	0.021	0.12	16	-10000	0	16
LPA/LPA1-2-3	-0.001	0.006	0.015	57	-10000	0	57
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0.001	0.002	81	-10000	0	81
BCAR1	0	0	-10000	0	-10000	0	0
stress fiber formation	0.055	0.061	0.12	250	-0.11	2	252
GNAZ	0.059	0.082	0.16	215	-10000	0	215
EGFR/PI3K-beta/Gab1	-0.006	0.011	0.013	16	-10000	0	16
positive regulation of dendritic cell cytokine production	-0.001	0.006	0.014	57	-10000	0	57
LPA/LPA2/MAGI-3	-0.001	0.002	0.003	50	-0.006	8	58
ARHGEF1	0.053	0.078	0.14	251	-10000	0	251
GNAI2	0.068	0.084	0.16	250	-10000	0	250
GNAI3	0.059	0.082	0.16	216	-10000	0	216
GNAI1	0.061	0.082	0.16	221	-10000	0	221
LPA/LPA3	-0.001	0.002	0.001	306	-10000	0	306
LPA/LPA2	-0.001	0.002	0.001	303	-0.007	1	304
LPA/LPA1	-0.003	0.004	0.001	300	-0.013	1	301
HB-EGF/EGFR	-0.007	0.01	0.001	338	-10000	0	338
HBEGF	-0.011	0.008	0	179	-10000	0	179
mol:DAG	0.016	0.031	0.061	60	-10000	0	60
cAMP biosynthetic process	0.068	0.072	0.14	251	-10000	0	251
NFKB1	-0.014	0.001	0	4	-10000	0	4
SRC	-0.014	0	-10000	0	-10000	0	0
GNB1	-0.015	0.002	0	6	-10000	0	6
LYN	0.036	0.053	0.083	258	-10000	0	258
GNAQ	0.03	0.035	0.066	250	-10000	0	250
LPAR2	0	0.001	0.002	108	-0.002	2	110
LPAR3	0	0.001	0.002	115	-10000	0	115
LPAR1	-0.002	0.002	0	266	-0.008	1	267
IL8	0.15	0.16	0.3	221	-10000	0	221
PTK2	0.064	0.075	0.14	250	-10000	0	250
Rac1/GDP	-0.009	0	-10000	0	-10000	0	0
CASP3	-0.003	0.004	0	320	-10000	0	320
EGFR	-0.006	0.009	0.003	253	-10000	0	253
PLCG1	0.03	0.034	0.065	250	-10000	0	250
PLD2	0.064	0.075	0.14	250	-10000	0	250
G12/G13	-0.006	0.01	0.015	50	-10000	0	50
PI3K-beta	-0.009	0.012	-10000	0	-0.17	1	1
cell migration	0.009	0.054	-10000	0	-0.22	21	21
SLC9A3R2	-0.014	0	-10000	0	-10000	0	0
PXN	0.055	0.061	0.12	250	-0.11	2	252
HRAS/GTP	0.003	0.021	0.12	16	-10000	0	16
RAC1	-0.014	0	-10000	0	-10000	0	0
MMP9	-0.009	0.007	0.001	190	-10000	0	190
PRKCE	-0.015	0.001	-10000	0	-10000	0	0
PRKCD	0.012	0.03	0.075	11	-10000	0	11
Gi(beta/gamma)	0.003	0.023	0.13	16	-10000	0	16
mol:LPA	-0.002	0.002	0	266	-0.008	1	267
TRIP6/p130 Cas/FAK1/Paxillin	0.018	0.046	0.11	96	-0.12	1	97
MAPKKK cascade	0.003	0.021	0.12	16	-10000	0	16
contractile ring contraction involved in cytokinesis	0.041	0.054	0.095	250	-0.24	2	252
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	0.03	0.035	0.066	250	-10000	0	250
GNA15	0.029	0.035	0.066	243	-10000	0	243
GNA12	-0.014	0.001	0	4	-10000	0	4
GNA13	-0.014	0.001	0	2	-10000	0	2
MAPT	0.041	0.057	0.098	250	-10000	0	250
GNA11	0.03	0.035	0.066	250	-10000	0	250
Rac1/GTP	-0.018	0.17	-10000	0	-0.83	21	21
MMP2	-0.006	0.005	0	250	-10000	0	250

×

Ras signaling in the CD4+ TCR pathway

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
ERK1-2/ELK1	-0.006	0.033	-10000	0	-0.17	15	15
MAP3K8	-0.007	0.013	0.019	107	-10000	0	107
FOS	0.041	0.089	0.19	125	-0.17	15	140
PRKCA	-0.003	0.021	0.034	125	-10000	0	125
PTPN7	0.001	0.029	0.053	125	-10000	0	125
HRAS	-0.008	0.011	0.012	127	-10000	0	127
PRKCB	0.006	0.011	0.025	125	-10000	0	125
NRAS	-0.006	0.01	0.005	233	-10000	0	233
RAS family/GTP	0	0.026	0.053	97	-10000	0	97
MAPK3	0.033	0.051	0.16	5	-10000	0	5
MAP2K1	0.026	0.047	0.1	135	-10000	0	135
ELK1	-0.007	0.015	0.02	125	-10000	0	125
BRAF	0.012	0.03	0.064	125	-10000	0	125
mol:GTP	0.001	0.002	0.004	125	-10000	0	125
MAPK1	0.022	0.084	-10000	0	-0.34	17	17
RAF1	0.012	0.03	0.064	125	-10000	0	125
KRAS	-0.008	0.011	0.011	134	-10000	0	134

×

FoxO family signaling

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
G6PC	0.016	0.028	-10000	0	-10000	0	0
PLK1	0.15	0.14	0.4	51	-10000	0	51
CDKN1B	0.19	0.14	0.34	202	-10000	0	202
FOXO3	0.16	0.14	0.3	182	-10000	0	182
KAT2B	0.025	0.023	0.043	301	-10000	0	301
FOXO1/SIRT1	0.025	0.038	0.16	7	-10000	0	7
CAT	0.14	0.12	0.39	33	-10000	0	33
CTNNB1	-0.014	0	-10000	0	-10000	0	0
AKT1	0.034	0.031	0.057	301	-10000	0	301
FOXO1	0.02	0.032	0.17	6	-10000	0	6
MAPK10	0.016	0.036	0.1	56	-10000	0	56
mol:GTP	0.003	0.005	0.015	49	-10000	0	49
FOXO4	0.055	0.1	0.25	72	-10000	0	72
response to oxidative stress	0.031	0.026	0.059	184	-10000	0	184
FOXO3A/SIRT1	0.16	0.13	0.3	184	-10000	0	184
XPO1	-0.011	0.008	0.014	48	-10000	0	48
EP300	0	0.014	0.014	174	-10000	0	174
BCL2L11	0.028	0.031	-10000	0	-10000	0	0
FOXO1/SKP2	0.016	0.029	0.14	5	-10000	0	5
mol:GDP	0.031	0.026	0.059	184	-10000	0	184
RAN	-0.004	0.013	0.014	189	-10000	0	189
GADD45A	0.14	0.14	0.44	56	-10000	0	56
YWHAQ	-0.014	0	-10000	0	-10000	0	0
FOXO1/14-3-3 family	-0.045	0.051	0.11	1	-0.19	7	8
MST1	0.029	0.029	0.051	301	-10000	0	301
CSNK1D	-0.014	0.001	0	2	-10000	0	2
CSNK1E	-0.014	0.001	0	1	-10000	0	1
FOXO4/14-3-3 family	-0.068	0.088	0.098	2	-0.15	233	235
YWHAB	-0.014	0.001	0	2	-10000	0	2
MAPK8	0.03	0.045	0.11	93	-10000	0	93
MAPK9	0.029	0.043	0.11	94	-10000	0	94
YWHAG	0	0	-10000	0	-10000	0	0
YWHAE	-0.014	0.001	0	2	-10000	0	2
YWHAZ	-0.014	0.002	0	6	-10000	0	6
SIRT1	0.003	0.019	0.044	45	-10000	0	45
SOD2	0.24	0.18	0.38	304	-10000	0	304
RBL2	0.13	0.11	0.33	52	-10000	0	52
RAL/GDP	0.031	0.031	0.066	173	-10000	0	173
CHUK	0.03	0.029	0.051	305	-10000	0	305
Ran/GTP	0.006	0.015	0.021	189	-10000	0	189
CSNK1G2	-0.014	0	-10000	0	-10000	0	0
RAL/GTP	0.041	0.042	0.087	174	-10000	0	174
CSNK1G1	-0.014	0	-10000	0	-10000	0	0
FASLG	0.028	0.031	-10000	0	-10000	0	0
SKP2	-0.014	0.001	0	2	-10000	0	2
USP7	-0.004	0.013	0.014	189	-10000	0	189
IKBKB	0.03	0.029	0.051	305	-10000	0	305
CCNB1	0.2	0.17	0.34	284	-10000	0	284
FOXO1-3a-4/beta catenin	0.17	0.15	0.33	205	-10000	0	205
proteasomal ubiquitin-dependent protein catabolic process	0.016	0.029	0.14	5	-10000	0	5
CSNK1A1	-0.014	0	-10000	0	-10000	0	0
SGK1	0.025	0.023	0.043	301	-10000	0	301
CSNK1G3	-0.014	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.011	0.025	0.035	189	-10000	0	189
ZFAND5	0.053	0.093	0.28	41	-10000	0	41
SFN	-0.013	0.003	0	33	-10000	0	33
CDK2	0	0.015	-10000	0	-10000	0	0
FOXO3A/14-3-3	-0.015	0.079	0.11	38	-0.15	55	93
CREBBP	0	0.015	-10000	0	-10000	0	0
FBXO32	0.14	0.12	0.27	180	-10000	0	180
BCL6	0.13	0.12	0.36	57	-10000	0	57
RALB	0	0.014	0.012	292	-10000	0	292
RALA	0	0.013	0.012	261	-10000	0	261
YWHAH	-0.007	0.007	0	284	-10000	0	284

×

Effects of Botulinum toxin

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
STX1A	0	0.001	0	512	-10000	0	512
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	-0.017	0.001	0	1	-10000	0	1
STXBP1	-0.001	0.004	0	479	-10000	0	479
ACh/CHRNA1	-0.021	0.014	-10000	0	-0.052	51	51
RAB3GAP2/RIMS1/UNC13B	-0.02	0.001	0	1	-10000	0	1
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	-0.014	0	-10000	0	-10000	0	0
mol:ACh	-0.019	0.016	-10000	0	-0.061	51	51
RAB3GAP2	-0.014	0	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	-0.001	0.005	-10000	0	-0.057	2	2
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	-0.021	0.014	-10000	0	-0.052	51	51
UNC13B	-0.014	0.001	0	1	-10000	0	1
CHRNA1	-0.014	0.001	0	3	-10000	0	3
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0	0.004	0.018	16	-10000	0	16
SNAP25	0	0	0	483	-10000	0	483
VAMP2	-0.001	0	0	49	-10000	0	49
SYT1	-0.001	0.003	0	495	-10000	0	495
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0	0.002	0	514	-10000	0	514
STX1A/SNAP25 fragment 1/VAMP2	-0.001	0.005	-10000	0	-0.057	2	2

×

PLK2 and PLK4 events

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.Total.Perturbations
PLK2	-0.01	0.006	0	155	-9999	155
PLK4	-0.014	0	-9999	0	-9999	0
regulation of centriole replication	-0.012	0.008	0	155	-9999	155

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	-0.014	0.001	0	2	-9999	2
EGFR	-0.009	0.007	0	194	-9999	194
EGF/EGFR	-0.009	0.01	0	304	-9999	304
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.012	0.011	0	241	-9999	241
mol:GTP	0	0	-10000	0	-9999	0
EDNRA	-0.01	0.006	0	154	-9999	154
response to oxidative stress	0	0	-10000	0	-9999	0
EGF	-0.014	0.001	0	2	-9999	2
EGF/EGFR dimer/SHC	-0.011	0.01	0	237	-9999	237
mol:GDP	-0.012	0.011	0	241	-9999	241
mol:Ca2+	0	0	-10000	0	-9999	0
EDN1	-0.014	0.002	0	9	-9999	9
GRB2/SOS1	-0.008	0.001	0	5	-9999	5
HRAS/GTP	-0.013	0.012	-10000	0	-9999	0
SHC1	-0.013	0.004	0	46	-9999	46
HRAS/GDP	-0.014	0.013	-10000	0	-9999	0
FRAP1	0.025	0.056	0.087	235	-9999	235
EGF/EGFR dimer	-0.011	0.008	0	196	-9999	196
SOS1	0	0	-10000	0	-9999	0
GRB2	-0.014	0.001	0	5	-9999	5
ETA receptor/Endothelin-1	-0.012	0.008	0	158	-9999	158

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.005	0.016	0.3	1	-10000	0	1
oxygen homeostasis	0.024	0.032	0.059	191	-10000	0	191
TCEB2	-0.014	0	-10000	0	-10000	0	0
TCEB1	-0.014	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.064	0.094	0.19	148	-10000	0	148
EPO	0.16	0.21	0.4	185	-10000	0	185
FIH (dimer)	0.026	0.039	0.069	186	-10000	0	186
APEX1	0.018	0.03	0.05	181	-10000	0	181
SERPINE1	0.022	0.12	0.39	16	-10000	0	16
FLT1	-0.006	0.012	-10000	0	-10000	0	0
ADORA2A	0.17	0.22	0.43	184	-10000	0	184
germ cell development	0.17	0.22	0.43	183	-10000	0	183
SLC11A2	0.18	0.23	0.44	187	-10000	0	187
BHLHE40	0.17	0.22	0.44	183	-10000	0	183
HIF1AN	0.026	0.039	0.069	186	-10000	0	186
HIF2A/ARNT/SIRT1	0.018	0.076	0.2	7	-10000	0	7
ETS1	-0.012	0.025	0.13	17	-10000	0	17
CITED2	-0.005	0.015	0.28	1	-10000	0	1
KDR	-0.005	0.021	0.3	2	-10000	0	2
PGK1	0.18	0.23	0.44	187	-10000	0	187
SIRT1	-0.015	0	-10000	0	-10000	0	0
response to hypoxia	-0.001	0	-10000	0	-10000	0	0
HIF2A/ARNT	0.035	0.12	0.32	7	-10000	0	7
EPAS1	0.12	0.16	0.3	191	-10000	0	191
SP1	-0.015	0.009	0.13	2	-10000	0	2
ABCG2	0.18	0.23	0.44	185	-10000	0	185
EFNA1	0.16	0.22	0.43	174	-10000	0	174
FXN	0.17	0.22	0.43	187	-10000	0	187
POU5F1	0.17	0.22	0.44	183	-10000	0	183
neuron apoptosis	-0.034	0.12	-10000	0	-0.32	7	7
EP300	-0.014	0	-10000	0	-10000	0	0
EGLN3	0.026	0.039	0.068	183	-10000	0	183
EGLN2	0.026	0.039	0.068	186	-10000	0	186
EGLN1	0.026	0.039	0.069	186	-10000	0	186
VHL/Elongin B/Elongin C	-0.014	0	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.018	0.03	0.05	181	-10000	0	181
SLC2A1	0.16	0.22	0.43	179	-10000	0	179
TWIST1	0.13	0.21	0.41	150	-10000	0	150
ELK1	-0.012	0.023	0.13	14	-10000	0	14
HIF2A/ARNT/Cbp/p300	0.02	0.08	0.21	7	-10000	0	7
VEGFA	0.002	0.11	0.44	17	-10000	0	17
CREBBP	-0.014	0	-10000	0	-10000	0	0

×

PDGFR-alpha signaling pathway

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	-0.004	0.021	0.034	112	-10000	0	112
PDGF/PDGFRA/CRKL	-0.006	0.02	0.031	112	-10000	0	112
positive regulation of JUN kinase activity	-0.005	0.019	0.031	99	-10000	0	99
CRKL	-0.014	0	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.006	0.02	0.031	112	-10000	0	112
AP1	-0.014	0.031	-10000	0	-0.26	2	2
mol:IP3	0.002	0.039	0.066	124	-10000	0	124
PLCG1	0.002	0.039	0.066	124	-10000	0	124
PDGF/PDGFRA/alphaV Integrin	-0.006	0.02	0.031	107	-10000	0	107
RAPGEF1	-0.014	0	-10000	0	-10000	0	0
CRK	-0.014	0	-10000	0	-10000	0	0
mol:Ca2+	0.002	0.039	0.066	124	-10000	0	124
CAV3	-0.014	0	-10000	0	-10000	0	0
CAV1	-0.005	0.007	0	324	-10000	0	324
SHC/Grb2/SOS1	-0.005	0.019	0.032	99	-10000	0	99
PDGF/PDGFRA/Shf	-0.001	0.014	0.025	112	-10000	0	112
FOS	0.051	0.13	0.3	112	-10000	0	112
JUN	0.001	0.028	0.051	124	-0.045	2	126
oligodendrocyte development	-0.006	0.02	0.031	107	-10000	0	107
GRB2	-0.014	0.001	0	5	-10000	0	5
PIK3R1	-0.013	0.004	0	36	-10000	0	36
mol:DAG	0.002	0.039	0.066	124	-10000	0	124
PDGF/PDGFRA	-0.004	0.021	0.035	112	-10000	0	112
actin cytoskeleton reorganization	-0.006	0.02	0.031	112	-10000	0	112
SRF	-0.02	0.006	0.015	2	-0.034	14	16
SHC1	-0.013	0.004	0	46	-10000	0	46
PI3K	-0.006	0.021	0.034	104	-10000	0	104
PDGF/PDGFRA/Crk/C3G	-0.007	0.022	0.034	112	-10000	0	112
JAK1	-0.008	0.015	0.019	112	-10000	0	112
ELK1/SRF	-0.013	0.027	0.072	39	-10000	0	39
SHB	-0.014	0	-10000	0	-10000	0	0
SHF	0	0	-10000	0	-10000	0	0
CSNK2A1	-0.019	0.009	0.03	2	-0.034	125	127
GO:0007205	0.014	0.051	0.082	163	-10000	0	163
SOS1	0	0	-10000	0	-10000	0	0
Ras protein signal transduction	-0.005	0.019	0.031	99	-10000	0	99
PDGF/PDGFRA/SHB	-0.006	0.02	0.031	112	-10000	0	112
PDGF/PDGFRA/Caveolin-1	-0.004	0.011	0.031	25	-10000	0	25
ITGAV	-0.014	0.002	0	16	-10000	0	16
ELK1	0.01	0.047	0.084	151	-10000	0	151
PIK3CA	-0.014	0.003	0	25	-10000	0	25
PDGF/PDGFRA/Crk	-0.006	0.02	0.031	112	-10000	0	112
JAK-STAT cascade	-0.008	0.015	0.019	112	-10000	0	112
cell proliferation	-0.001	0.014	0.025	112	-10000	0	112

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.008	0.001	0	2	-10000	0	2
GNB1/GNG2	-0.005	0.011	0.015	122	-10000	0	122
regulation of S phase of mitotic cell cycle	-0.004	0.008	0.009	114	-10000	0	114
GNAO1	-0.001	0.004	0	481	-10000	0	481
HRAS	-0.008	0.011	0.012	127	-10000	0	127
SHBG/T-DHT	-0.007	0.001	0.006	3	-10000	0	3
PELP1	-0.008	0.011	0.012	125	-10000	0	125
AKT1	-0.009	0.001	0	4	-10000	0	4
MAP2K1	0.001	0.054	0.094	125	-0.14	2	127
T-DHT/AR	-0.004	0.008	0.01	130	-10000	0	130
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0.001	0.002	0.004	125	-0.006	2	127
GNAI2	-0.014	0.001	0	1	-10000	0	1
GNAI3	-0.012	0.005	0	65	-10000	0	65
GNAI1	-0.012	0.005	0	81	-10000	0	81
mol:GDP	-0.009	0.007	-10000	0	-10000	0	0
cell proliferation	0.017	0.1	0.19	125	-0.37	2	127
PIK3CA	-0.014	0.003	0	25	-10000	0	25
FOS	0.046	0.14	0.28	125	-0.51	2	127
mol:Ca2+	0	0.003	0.019	15	-10000	0	15
MAPK3	0.01	0.079	0.15	125	-0.26	2	127
MAPK1	0.011	0.094	0.19	3	-0.34	19	22
PIK3R1	-0.013	0.004	0	36	-10000	0	36
mol:IP3	0.001	0.002	0.005	125	-0.004	2	127
cAMP biosynthetic process	0	0.001	-10000	0	-10000	0	0
GNG2	0	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	0.001	0.002	0.005	125	-0.004	2	127
HRAS/GTP	0.002	0.041	0.076	122	-0.068	2	124
actin cytoskeleton reorganization	-0.017	0.007	0.016	2	-10000	0	2
SRC	-0.008	0.011	0.012	125	-10000	0	125
voltage-gated calcium channel activity	0.001	0.002	0.005	125	-0.004	2	127
PI3K	-0.012	0.004	0	60	-10000	0	60
apoptosis	-0.028	0.11	0.36	2	-0.21	125	127
T-DHT/AR/PELP1	-0.005	0.015	0.021	122	-10000	0	122
HRAS/GDP	-0.009	0.016	0.065	5	-10000	0	5
CREB1	-0.021	0.044	0.28	3	-0.38	2	5
RAC1-CDC42/GTP	-0.01	0.017	0.019	116	-10000	0	116
AR	-0.008	0.011	0.011	130	-10000	0	130
GNB1	-0.014	0.002	0	6	-10000	0	6
RAF1	0	0.046	0.079	111	-0.1	2	113
RAC1-CDC42/GDP	-0.01	0.022	0.056	30	-10000	0	30
T-DHT/AR/PELP1/Src	-0.006	0.022	0.035	122	-0.037	2	124
MAP2K2	0.001	0.054	0.094	125	-0.14	2	127
T-DHT/AR/PELP1/Src/PI3K	-0.004	0.008	0.009	114	-10000	0	114
GNAZ	-0.012	0.005	0	72	-10000	0	72
SHBG	-0.014	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.13	0.072	-10000	0	-0.15	444	444
mol:T-DHT	0	0	-10000	0	-10000	0	0
RAC1	-0.014	0	-10000	0	-10000	0	0
GNRH1	-0.008	0	-10000	0	-10000	0	0
Gi family/GTP	0	0.006	0.05	5	-0.069	1	6
CDC42	-0.014	0	-10000	0	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.013	0.007	0	125	-9999	0	125
ATM	-0.014	0.003	0	25	-9999	0	25
UBE2D3	-0.014	0.001	0	1	-9999	0	1
PRKDC	-0.014	0.003	0	23	-9999	0	23
ATR	-0.014	0	-10000	0	-9999	0	0
UBE2L3	-0.014	0	-10000	0	-9999	0	0
FANCD2	-0.005	0.001	-10000	0	-9999	0	0
protein ubiquitination	-0.019	0.012	-10000	0	-9999	0	0
XRCC5	-0.014	0	-10000	0	-9999	0	0
XRCC6	-0.014	0	-10000	0	-9999	0	0
M/R/N Complex	-0.02	0	-10000	0	-9999	0	0
MRE11A	-0.014	0	-10000	0	-9999	0	0
DNA-PK	-0.019	0.004	0	23	-9999	0	23
FA complex/FANCD2/Ubiquitin	-0.005	0.007	-10000	0	-9999	0	0
FANCF	-0.014	0.001	0	2	-9999	0	2
BRCA1	-0.014	0.001	0	5	-9999	0	5
CCNE1	-0.014	0.002	0	7	-9999	0	7
CDK2/Cyclin E1	-0.016	0.004	0	30	-9999	0	30
FANCG	-0.012	0.005	0	66	-9999	0	66
BRCA1/BACH1/BARD1	-0.013	0.007	0	126	-9999	0	126
FANCE	-0.014	0.001	0	1	-9999	0	1
FANCC	-0.014	0	-10000	0	-9999	0	0
NBN	-0.014	0	-10000	0	-9999	0	0
FANCA	-0.014	0	-10000	0	-9999	0	0
DNA repair	0.062	0.076	0.17	133	-9999	0	133
BRCA1/BARD1/ubiquitin	-0.013	0.007	0	126	-9999	0	126
BARD1/DNA-PK	-0.017	0.01	0	138	-9999	0	138
FANCL	0	0	-10000	0	-9999	0	0
mRNA polyadenylation	0.013	0.007	-10000	0	0	125	125
BRCA1/BARD1/CTIP/M/R/N Complex	0.029	0.034	0.057	297	-9999	0	297
BRCA1/BACH1/BARD1/TopBP1	-0.015	0.009	0	126	-9999	0	126
BRCA1/BARD1/P53	-0.016	0.011	0	166	-9999	0	166
BARD1/CSTF1/BRCA1	-0.015	0.009	0	126	-9999	0	126
BRCA1/BACH1	-0.014	0.001	0	5	-9999	0	5
BARD1	-0.011	0.006	0	125	-9999	0	125
PCNA	-0.005	0.007	0	342	-9999	0	342
BRCA1/BARD1/UbcH5C	-0.015	0.009	0	127	-9999	0	127
BRCA1/BARD1/UbcH7	-0.015	0.009	0	126	-9999	0	126
BRCA1/BARD1/RAD51/PCNA	-0.008	0.011	0	359	-9999	0	359
BARD1/DNA-PK/P53	-0.018	0.013	-10000	0	-9999	0	0
BRCA1/BARD1/Ubiquitin	-0.013	0.007	0	126	-9999	0	126
BRCA1/BARD1/CTIP	-0.005	0.009	0	423	-9999	0	423
FA complex	-0.008	0.004	0.05	1	-9999	0	1
BARD1/EWS	-0.013	0.007	0	125	-9999	0	125
RBBP8	-0.004	0.007	0	411	-9999	0	411
TP53	-0.012	0.005	0	69	-9999	0	69
TOPBP1	-0.014	0.001	0	1	-9999	0	1
G1/S transition of mitotic cell cycle	0.016	0.011	-10000	0	0	166	166
BRCA1/BARD1	-0.02	0.012	-10000	0	-9999	0	0
CSTF1	-0.014	0	-10000	0	-9999	0	0
BARD1/EWS-Fli1	-0.007	0.004	0	125	-9999	0	125
CDK2	-0.013	0.003	0	27	-9999	0	27
UniProt:Q9BZD1	0	0	-10000	0	-9999	0	0
RAD51	-0.014	0	-10000	0	-9999	0	0
RAD50	-0.014	0	-10000	0	-9999	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.013	0.007	0	126	-9999	0	126
EWSR1	-0.014	0	-10000	0	-9999	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0	0	-10000	0	-10000	0	0
GNB1/GNG2	0.007	0.03	0.051	162	-10000	0	162
mol:DAG	0.012	0.042	0.06	208	-10000	0	208
PLCG1	0.013	0.043	0.061	208	-10000	0	208
YES1	0.004	0.027	0.049	135	-10000	0	135
FZD3	-0.014	0.002	0	16	-10000	0	16
FZD6	-0.012	0.006	0	100	-10000	0	100
G protein	0.011	0.04	0.099	42	-10000	0	42
MAP3K7	0.001	0.036	0.085	45	-10000	0	45
mol:Ca2+	0.012	0.041	0.059	208	-10000	0	208
mol:IP3	0.012	0.042	0.06	208	-10000	0	208
NLK	0.006	0.054	-10000	0	-0.71	3	3
GNB1	-0.014	0.002	0	6	-10000	0	6
CAMK2A	0.006	0.038	0.095	45	-10000	0	45
MAP3K7IP1	-0.014	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.006	0.005	-10000	0	-10000	0	0
CSNK1A1	-0.014	0	-10000	0	-10000	0	0
GNAS	0.006	0.029	0.049	163	-10000	0	163
GO:0007205	0.013	0.04	0.1	46	-10000	0	46
WNT6	-0.014	0	-10000	0	-10000	0	0
WNT4	-0.014	0.001	0	2	-10000	0	2
NFAT1/CK1 alpha	0.009	0.045	0.11	59	-10000	0	59
GNG2	0	0	-10000	0	-10000	0	0
WNT5A	-0.01	0.007	0	168	-10000	0	168
WNT11	-0.014	0.001	0	2	-10000	0	2
CDC42	0.005	0.032	0.084	30	-10000	0	30

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	-0.005	0.01	-10000	0	-0.021	111	111
BUB1B	0.055	0.063	0.11	269	-10000	0	269
PLK1	0.004	0.024	0.083	38	-10000	0	38
PLK1S1	0.01	0.016	0.036	112	-10000	0	112
KIF2A	0.009	0.023	0.071	36	-10000	0	36
regulation of mitotic centrosome separation	0.016	0.027	0.057	112	-10000	0	112
GOLGA2	-0.014	0	-10000	0	-10000	0	0
Hec1/SPC24	0.003	0.013	0.043	15	-10000	0	15
WEE1	0.05	0.049	0.13	105	-10000	0	105
cytokinesis	0.059	0.074	0.15	198	-10000	0	198
PP2A-alpha B56	0.033	0.017	-10000	0	-10000	0	0
AURKA	0.014	0.022	0.087	25	-10000	0	25
PICH/PLK1	0.007	0.031	0.058	131	-10000	0	131
CENPE	0.024	0.058	0.15	77	-10000	0	77
RhoA/GTP	-0.009	0.001	0	2	-10000	0	2
positive regulation of microtubule depolymerization	0.009	0.023	0.074	33	-10000	0	33
PPP2CA	-0.014	0.001	0	4	-10000	0	4
FZR1	-0.014	0	-10000	0	-10000	0	0
TPX2	0.033	0.032	0.066	208	-10000	0	208
PAK1	-0.008	0.011	0.013	108	-10000	0	108
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	-0.014	0	-10000	0	-10000	0	0
CLSPN	0.011	0.016	0.077	7	-10000	0	7
GORASP1	-0.014	0	-10000	0	-10000	0	0
metaphase	0.001	0.002	0.009	22	-10000	0	22
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.01	0.016	0.036	112	-10000	0	112
G2 phase of mitotic cell cycle	0.001	0.002	0.006	26	-10000	0	26
STAG2	-0.013	0.003	0	27	-10000	0	27
GRASP65/GM130/RAB1/GTP	0.003	0.006	-10000	0	-10000	0	0
spindle elongation	0.016	0.027	0.057	112	-10000	0	112
ODF2	-0.008	0.011	0.013	108	-10000	0	108
BUB1	0.002	0.004	-10000	0	-10000	0	0
TPT1	0.011	0.016	0.072	13	-10000	0	13
CDC25C	0.011	0.015	0.079	5	-10000	0	5
CDC25B	0.005	0.014	0.015	352	-10000	0	352
SGOL1	0.005	0.01	0.021	111	-10000	0	111
RHOA	-0.014	0.001	0	2	-10000	0	2
CCNB1/CDK1	0.005	0.008	-10000	0	-10000	0	0
CDC14B	-0.008	0.001	-10000	0	-10000	0	0
CDC20	-0.006	0.007	0	303	-10000	0	303
PLK1/PBIP1	-0.001	0.003	-10000	0	-10000	0	0
mitosis	0.002	0.004	0.013	19	-10000	0	19
FBXO5	0.049	0.06	0.1	257	-10000	0	257
CDC2	-0.001	0.011	0.012	174	-10000	0	174
NDC80	-0.009	0.007	0	183	-10000	0	183
metaphase plate congression	0.012	0.017	0.086	5	-10000	0	5
ERCC6L	0.003	0.025	0.061	71	-10000	0	71
NLP/gamma Tubulin	0.012	0.019	0.042	109	-10000	0	109
microtubule cytoskeleton organization	0.011	0.016	0.072	13	-10000	0	13
G2/M transition DNA damage checkpoint	0.001	0.002	0.005	19	-10000	0	19
PPP1R12A	-0.013	0.003	0.011	8	-10000	0	8
interphase	0.001	0.002	0.005	19	-10000	0	19
PLK1/PRC1-2	0	0.014	0.042	6	-10000	0	6
GRASP65/GM130/RAB1/GTP/PLK1	0.015	0.027	0.05	112	-10000	0	112
RAB1A	-0.014	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.013	0.035	0.13	31	-10000	0	31
mitotic prometaphase	0.001	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.002	0.003	-10000	0	-10000	0	0
microtubule-based process	0.003	0.014	0.042	18	-10000	0	18
Golgi organization	0.016	0.027	0.057	112	-10000	0	112
Cohesin/SA2	0.013	0.022	0.048	98	-10000	0	98
PPP1CB/MYPT1	-0.01	0.013	0.016	108	-10000	0	108
KIF20A	-0.009	0.007	0	186	-10000	0	186
APC/C/CDC20	-0.001	0.009	0.041	2	-10000	0	2
PPP2R1A	-0.014	0.002	0	16	-10000	0	16
chromosome segregation	-0.001	0.003	-10000	0	-10000	0	0
PRC1	-0.008	0.007	0	224	-10000	0	224
ECT2	0.051	0.074	0.15	184	-10000	0	184
C13orf34	0.013	0.036	0.12	36	-10000	0	36
NUDC	0.012	0.017	0.086	5	-10000	0	5
regulation of attachment of spindle microtubules to kinetochore	0.055	0.063	0.11	269	-10000	0	269
spindle assembly	0.013	0.024	0.05	112	-10000	0	112
spindle stabilization	0.01	0.016	0.036	112	-10000	0	112
APC/C/HCDH1	-0.013	0.001	-10000	0	-10000	0	0
MKLP2/PLK1	0.003	0.014	0.042	18	-10000	0	18
CCNB1	-0.003	0.009	0.011	71	-10000	0	71
PPP1CB	-0.013	0.003	0.011	7	-10000	0	7
BTRC	-0.014	0	-10000	0	-10000	0	0
ROCK2	0.012	0.019	0.093	5	-0.1	2	7
TUBG1	0.011	0.018	0.072	22	-10000	0	22
G2/M transition of mitotic cell cycle	0.011	0.031	0.063	131	-10000	0	131
MLF1IP	-0.001	0.003	0	449	-10000	0	449
INCENP	-0.009	0.009	0.011	90	-10000	0	90

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.003	0.028	0.19	1	-10000	0	1
UGCG	0.017	0.028	-10000	0	-10000	0	0
AKT1/mTOR/p70S6K/Hsp90/TERT	0.037	0.087	0.18	124	-10000	0	124
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	0.017	0.028	-10000	0	-10000	0	0
mol:DAG	0.004	0.003	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.016	0.077	0.18	88	-10000	0	88
FRAP1	0.041	0.11	0.22	129	-10000	0	129
FOXO3	0.041	0.1	0.22	128	-0.21	2	130
AKT1	0.001	0.062	0.28	20	-0.22	2	22
GAB2	-0.006	0.014	0.018	135	-10000	0	135
SMPD1	0.017	0.028	-10000	0	-10000	0	0
SGMS1	0.016	0.028	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	-0.006	0.012	0.016	108	-10000	0	108
CALM1	-0.013	0.003	0	27	-10000	0	27
cell proliferation	0.042	0.079	0.18	128	-10000	0	128
EIF3A	-0.014	0	-10000	0	-10000	0	0
PI3K	-0.005	0.021	0.035	108	-10000	0	108
RPS6KB1	0.013	0.027	0.24	1	-10000	0	1
mol:sphingomyelin	0.004	0.003	-10000	0	-10000	0	0
natural killer cell activation	0.002	0.004	0.009	137	-10000	0	137
JAK3	-0.006	0.015	0.018	137	-10000	0	137
PIK3R1	-0.006	0.014	0.02	117	-10000	0	117
JAK1	-0.006	0.014	0.018	136	-10000	0	136
NFKB1	-0.014	0.001	0	4	-10000	0	4
MYC	0.066	0.14	0.3	133	-10000	0	133
MYB	0.008	0.038	0.32	4	-10000	0	4
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.033	0.084	0.17	127	-0.2	2	129
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.021	0.024	0.21	1	-10000	0	1
mol:PI-3-4-5-P3	0.032	0.084	0.17	127	-0.2	2	129
Rac1/GDP	-0.006	0.023	0.031	117	-10000	0	117
T cell proliferation	0.031	0.079	0.16	128	-0.19	2	130
SHC1	-0.006	0.013	0.018	115	-10000	0	115
RAC1	-0.014	0.001	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.001	0.011	0.093	8	-10000	0	8
PRKCZ	0.031	0.08	0.16	128	-0.19	2	130
NF kappa B1 p50/RelA	0.031	0.099	0.2	126	-10000	0	126
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.001	0.026	0.15	3	-10000	0	3
HSP90AA1	-0.014	0	-10000	0	-10000	0	0
RELA	-0.014	0	-10000	0	-10000	0	0
IL2RA	-0.006	0.014	0.018	135	-10000	0	135
IL2RB	-0.006	0.014	0.018	133	-10000	0	133
TERT	-0.014	0	-10000	0	-10000	0	0
E2F1	0.009	0.031	0.25	8	-10000	0	8
SOS1	0.003	0.005	0.01	137	-10000	0	137
RPS6	-0.014	0	-10000	0	-10000	0	0
mol:cAMP	0	0.006	-10000	0	-0.05	8	8
PTPN11	-0.006	0.015	0.02	137	-10000	0	137
IL2RG	-0.006	0.015	0.019	128	-10000	0	128
actin cytoskeleton organization	0.031	0.079	0.16	128	-0.19	2	130
GRB2	-0.006	0.014	0.019	136	-10000	0	136
IL2	-0.006	0.015	0.019	137	-10000	0	137
PIK3CA	-0.006	0.015	0.019	127	-10000	0	127
Rac1/GTP	0.013	0.053	0.11	117	-10000	0	117
LCK	-0.006	0.015	0.019	134	-10000	0	134
BCL2	0.037	0.098	0.24	33	-10000	0	33

×

Reelin signaling pathway

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
CDK5R1/CDK5	-0.013	0.007	0	116	-10000	0	116
VLDLR	-0.014	0.001	0	3	-10000	0	3
CRKL	-0.014	0	-10000	0	-10000	0	0
LRPAP1	-0.014	0	-10000	0	-10000	0	0
FYN	-0.014	0.003	0	21	-10000	0	21
ITGA3	-0.014	0.003	0	19	-10000	0	19
RELN/VLDLR/Fyn	-0.009	0.01	0	295	-10000	0	295
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.027	0	-10000	0	-10000	0	0
AKT1	-0.006	0.007	-10000	0	-10000	0	0
MAP2K7	-0.014	0	-10000	0	-10000	0	0
RAPGEF1	-0.014	0	-10000	0	-10000	0	0
DAB1	-0.014	0	-10000	0	-10000	0	0
RELN/LRP8/DAB1	-0.008	0.009	0	282	-10000	0	282
LRPAP1/LRP8	-0.017	0	-10000	0	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.01	0.011	0	294	-10000	0	294
DAB1/alpha3/beta1 Integrin	-0.016	0.017	-10000	0	-10000	0	0
long-term memory	-0.01	0.015	-10000	0	-10000	0	0
DAB1/LIS1	-0.014	0.015	-10000	0	-10000	0	0
DAB1/CRLK/C3G	-0.016	0.017	-10000	0	-10000	0	0
PIK3CA	-0.014	0.003	0	25	-10000	0	25
DAB1/NCK2	-0.014	0.015	-10000	0	-10000	0	0
ARHGEF2	-0.014	0	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.01	0.007	0	174	-10000	0	174
CDK5R1	-0.011	0.006	0	101	-10000	0	101
RELN	-0.007	0.007	0	282	-10000	0	282
PIK3R1	-0.013	0.004	0	36	-10000	0	36
RELN/LRP8/Fyn	-0.009	0.01	0	294	-10000	0	294
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.009	0.013	-10000	0	-10000	0	0
MAPK8	-0.014	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.008	0.009	0	283	-10000	0	283
ITGB1	-0.014	0	-10000	0	-10000	0	0
MAP1B	-0.01	0.013	0.079	2	-10000	0	2
RELN/LRP8	-0.009	0.01	0	282	-10000	0	282
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.012	0.014	-10000	0	-10000	0	0
PI3K	-0.015	0.005	0	60	-10000	0	60
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	-0.016	0.003	0	19	-10000	0	19
RAP1A	-0.004	0.033	0.12	2	-10000	0	2
PAFAH1B1	-0.014	0.002	0	6	-10000	0	6
MAPK8IP1	-0.014	0	-10000	0	-10000	0	0
CRLK/C3G	-0.017	0	-10000	0	-10000	0	0
GRIN2B	-0.014	0	-10000	0	-10000	0	0
NCK2	-0.014	0.001	0	1	-10000	0	1
neuron differentiation	-0.044	0.034	-10000	0	-0.075	282	282
neuron adhesion	-0.01	0.037	0.11	19	-10000	0	19
LRP8	-0.014	0	-10000	0	-10000	0	0
GSK3B	-0.006	0.013	0.085	1	-10000	0	1
RELN/VLDLR/DAB1/Fyn	-0.01	0.011	-10000	0	-10000	0	0
MAP3K11	-0.014	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.004	0.005	-10000	0	-10000	0	0
CDK5	-0.013	0.003	0	33	-10000	0	33
MAPT	-0.004	0.005	-10000	0	-10000	0	0
neuron migration	-0.051	0.051	0.09	1	-0.12	182	183
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.044	0.034	-10000	0	-0.076	282	282
RELN/VLDLR	-0.011	0.012	0	283	-10000	0	283

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.005	0.023	0.033	215	-10000	0	215
HSPA8	-0.017	0.004	0	3	-10000	0	3
SMAD3/SMAD4/ER alpha	-0.011	0.038	0.096	36	-10000	0	36
AKT1	-0.012	0.009	0.015	6	-10000	0	6
GSC	-0.007	0.014	0.049	1	-0.044	33	34
NKX2-5	-0.012	0.012	0.015	86	-10000	0	86
muscle cell differentiation	-0.015	0.05	-10000	0	-0.15	27	27
SMAD2-3/SMAD4/SP1	0.019	0.082	0.25	41	-10000	0	41
SMAD4	0.008	0.046	0.092	59	-10000	0	59
CBFB	-0.014	0.001	0	4	-10000	0	4
SAP18	-0.015	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.012	0.039	0.061	203	-10000	0	203
SMAD3/SMAD4/VDR	0.023	0.061	0.12	129	-10000	0	129
MYC	-0.01	0.006	-10000	0	-10000	0	0
CDKN2B	-0.012	0.037	-10000	0	-10000	0	0
AP1	0.018	0.06	0.12	75	-10000	0	75
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.005	0.024	0.07	17	-10000	0	17
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.002	0.03	-10000	0	-10000	0	0
SP3	-0.014	0.012	0.076	7	-10000	0	7
CREB1	-0.014	0	-10000	0	-10000	0	0
FOXH1	-0.012	0.012	0.015	86	-10000	0	86
SMAD3/SMAD4/GR	-0.015	0.042	0.091	19	-0.13	18	37
GATA3	-0.024	0.003	-10000	0	-10000	0	0
SKI/SIN3/HDAC complex/NCoR1	-0.003	0.021	0.041	74	-10000	0	74
MEF2C/TIF2	0.005	0.045	0.08	65	-10000	0	65
endothelial cell migration	-0.13	0.15	-10000	0	-0.32	214	214
MAX	-0.038	0.031	-10000	0	-0.075	215	215
RBBP7	-0.015	0.001	-10000	0	-10000	0	0
RBBP4	-0.012	0.006	0	100	-10000	0	100
RUNX2	-0.014	0	-10000	0	-10000	0	0
RUNX3	-0.014	0.001	0	3	-10000	0	3
RUNX1	-0.014	0	-10000	0	-10000	0	0
CTBP1	-0.014	0.002	0	7	-10000	0	7
NR3C1	-0.038	0.031	-10000	0	-0.075	215	215
VDR	-0.014	0	-10000	0	-10000	0	0
CDKN1A	0.089	0.14	0.42	51	-10000	0	51
KAT2B	0.003	0.004	0.008	215	-10000	0	215
SMAD2/SMAD2/SMAD4/FOXH1	0.002	0.036	0.068	57	-10000	0	57
DCP1A	-0.014	0	-10000	0	-10000	0	0
SKI	-0.015	0.001	-10000	0	-10000	0	0
SERPINE1	0.13	0.15	0.32	212	-10000	0	212
SMAD3/SMAD4/ATF2	-0.006	0.038	0.094	43	-10000	0	43
SMAD3/SMAD4/ATF3	-0.006	0.034	0.09	34	-10000	0	34
SAP30	-0.015	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.021	0.051	0.083	214	-10000	0	214
JUN	0.048	0.08	0.15	144	-10000	0	144
SMAD3/SMAD4/IRF7	-0.004	0.045	0.1	52	-10000	0	52
TFE3	0.034	0.056	0.081	285	-10000	0	285
COL1A2	0.035	0.095	0.25	84	-10000	0	84
mesenchymal cell differentiation	0.006	0.038	-10000	0	-0.093	43	43
DLX1	0	0	-10000	0	-10000	0	0
TCF3	-0.014	0	-10000	0	-10000	0	0
FOS	-0.001	0.019	0.037	11	-10000	0	11
SMAD3/SMAD4/Max	-0.015	0.042	0.091	20	-0.13	18	38
Cbp/p300/SNIP1	0.003	0.029	0.038	215	-10000	0	215
ZBTB17	-0.014	0	-10000	0	-10000	0	0
LAMC1	0	0.038	0.096	25	-10000	0	25
TGIF2/HDAC complex/SMAD3/SMAD4	-0.006	0.038	0.094	43	-10000	0	43
IRF7	-0.019	0.003	-10000	0	-10000	0	0
ESR1	-0.022	0.013	0.11	4	-10000	0	4
HNF4A	-0.014	0	-10000	0	-10000	0	0
MEF2C	0.005	0.043	0.081	65	-10000	0	65
SMAD2-3/SMAD4	-0.007	0.038	0.1	17	-10000	0	17
Cbp/p300/Src-1	0.01	0.037	0.055	211	-10000	0	211
IGHV3OR16-13	-0.004	0.007	-10000	0	-10000	0	0
TGIF2/HDAC complex	-0.014	0.002	0	8	-10000	0	8
CREBBP	0.002	0.019	0.025	215	-10000	0	215
SKIL	-0.014	0	-10000	0	-10000	0	0
HDAC1	-0.013	0.005	0	65	-10000	0	65
HDAC2	-0.015	0.002	0	5	-10000	0	5
SNIP1	-0.016	0.003	-10000	0	-10000	0	0
GCN5L2	0.003	0.02	0.027	215	-10000	0	215
SMAD3/SMAD4/TFE3	0.005	0.048	0.13	28	-10000	0	28
MSG1/HSC70	-0.019	0.005	-10000	0	-10000	0	0
SMAD2	-0.013	0.012	0.035	1	-10000	0	1
SMAD3	0.017	0.056	0.085	169	-10000	0	169
SMAD3/E2F4-5/DP1/p107/SMAD4	0.013	0.04	0.077	125	-10000	0	125
SMAD2/SMAD2/SMAD4	0.027	0.036	0.084	79	-10000	0	79
NCOR1	-0.015	0.001	-10000	0	-10000	0	0
NCOA2	-0.014	0	-10000	0	-10000	0	0
NCOA1	-0.014	0.002	0	14	-10000	0	14
MYOD/E2A	-0.017	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.035	0.09	0.19	95	-10000	0	95
IFNB1	0.037	0.076	0.12	187	-10000	0	187
SMAD3/SMAD4/MEF2C	-0.002	0.048	0.13	22	-10000	0	22
CITED1	-0.013	0.003	0	25	-10000	0	25
SMAD2-3/SMAD4/ARC105	-0.001	0.048	0.13	37	-10000	0	37
RBL1	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.006	0.029	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	-0.02	0.002	0	7	-10000	0	7
SMAD7	0.04	0.084	0.18	121	-10000	0	121
MYC/MIZ-1	-0.012	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4	0.1	0.1	0.22	206	-10000	0	206
IL10	0.033	0.077	0.14	128	-10000	0	128
PIASy/HDAC complex	-0.022	0.01	-10000	0	-0.033	215	215
PIAS3	-0.002	0.015	0.016	214	-10000	0	214
CDK2	0.002	0.019	0.024	208	-10000	0	208
IL5	0.033	0.077	0.13	139	-10000	0	139
CDK4	0.002	0.012	0.027	88	-10000	0	88
PIAS4	-0.022	0.01	-10000	0	-0.033	215	215
ATF3	-0.011	0.006	0	108	-10000	0	108
SMAD3/SMAD4/SP1	0.018	0.083	0.26	38	-10000	0	38
FOXG1	-0.015	0.009	-10000	0	-0.038	48	48
FOXO3	-0.015	0.007	-10000	0	-10000	0	0
FOXO1	-0.016	0.005	-10000	0	-10000	0	0
FOXO4	-0.016	0.005	-10000	0	-10000	0	0
heart looping	0.005	0.043	0.08	65	-10000	0	65
CEBPB	-0.014	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.006	0.032	0.091	32	-10000	0	32
MYOD1	-0.014	0	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.006	0.038	0.094	43	-10000	0	43
SMAD3/SMAD4/GATA3	-0.005	0.052	0.11	62	-10000	0	62
SnoN/SIN3/HDAC complex/NCoR1	-0.014	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.011	0.055	0.098	117	-10000	0	117
SMAD3/SMAD4/SP1-3	0.02	0.081	0.25	38	-10000	0	38
MED15	-0.014	0	-10000	0	-10000	0	0
SP1	0.031	0.053	0.078	279	-10000	0	279
SIN3B	-0.015	0.001	-10000	0	-10000	0	0
SIN3A	-0.001	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.001	0.039	0.071	57	-10000	0	57
ITGB5	0.074	0.11	0.19	204	-10000	0	204
TGIF/SIN3/HDAC complex/CtBP	0.016	0.021	0.041	124	-10000	0	124
SMAD3/SMAD4/AR	-0.006	0.038	0.094	43	-10000	0	43
AR	-0.014	0.002	0	8	-10000	0	8
negative regulation of cell growth	0.019	0.045	0.13	47	-10000	0	47
SMAD3/SMAD4/MYOD	-0.006	0.038	0.094	43	-10000	0	43
E2F5	-0.014	0	-10000	0	-10000	0	0
E2F4	-0.014	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.01	0.043	0.083	96	-10000	0	96
SMAD2-3/SMAD4/FOXO1-3a-4	0.003	0.026	-10000	0	-10000	0	0
TFDP1	-0.014	0.002	0	15	-10000	0	15
SMAD3/SMAD4/AP1	0	0.046	0.13	22	-10000	0	22
SMAD3/SMAD4/RUNX2	-0.006	0.038	0.094	43	-10000	0	43
TGIF2	-0.014	0.002	0	8	-10000	0	8
TGIF1	-0.004	0.006	0	371	-10000	0	371
ATF2	-0.014	0	-10000	0	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.15	0.16	0.49	57	-10000	0	57
CRP	0.15	0.16	0.49	58	-10000	0	58
cell cycle arrest	0.16	0.17	0.46	87	-10000	0	87
TIMP1	0.26	0.2	0.5	151	-10000	0	151
IL6ST	0.016	0.022	0.045	128	-10000	0	128
Rac1/GDP	0.067	0.088	0.2	123	-10000	0	123
AP1	0.13	0.11	0.24	139	-0.26	2	141
GAB2	-0.012	0.008	0.021	24	-10000	0	24
TNFSF11	0.15	0.16	0.49	58	-10000	0	58
HSP90B1	0.052	0.071	0.42	3	-0.5	1	4
GAB1	-0.013	0.006	0.02	16	-10000	0	16
MAPK14	0.01	0.036	0.2	2	-10000	0	2
AKT1	0.013	0.035	0.29	4	-10000	0	4
FOXO1	0.01	0.038	0.27	5	-10000	0	5
MAP2K6	0.038	0.06	0.19	43	-10000	0	43
mol:GTP	0.002	0.002	0.009	40	-10000	0	40
MAP2K4	0.09	0.12	0.26	127	-10000	0	127
MITF	0.056	0.079	0.18	120	-10000	0	120
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	-0.014	0.001	0	1	-10000	0	1
A2M	-0.005	0.12	0.3	23	-0.88	7	30
CEBPB	-0.014	0.008	0.14	1	-10000	0	1
GRB2/SOS1/GAB family/SHP2	0.042	0.052	0.19	25	-10000	0	25
STAT3	0.15	0.17	0.42	118	-10000	0	118
STAT1	0.031	0.036	0.26	1	-10000	0	1
CEBPD	0.15	0.16	0.49	58	-10000	0	58
PIK3CA	-0.013	0.005	0.03	5	-10000	0	5
PI3K	-0.014	0.009	0.028	14	-10000	0	14
JUN	-0.012	0.006	0.012	33	-10000	0	33
PIAS3/MITF	0.053	0.074	0.16	120	-10000	0	120
MAPK11	0.01	0.036	0.2	2	-10000	0	2
STAT3 (dimer)/FOXO1	0.14	0.16	0.39	117	-10000	0	117
GRB2/SOS1/GAB family	0.034	0.049	0.14	41	-10000	0	41
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	0.03	0.053	0.12	108	-10000	0	108
GRB2	-0.013	0.006	0.02	16	-10000	0	16
JAK2	-0.014	0	-10000	0	-10000	0	0
LBP	0.14	0.15	0.46	62	-10000	0	62
PIK3R1	-0.012	0.006	0.024	8	-10000	0	8
JAK1	0.008	0.015	0.032	45	-10000	0	45
MYC	0.17	0.19	0.5	102	-10000	0	102
FGG	0.15	0.17	0.5	59	-10000	0	59
macrophage differentiation	0.16	0.17	0.46	87	-10000	0	87
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.027	0.041	0.086	91	-10000	0	91
JUNB	0.15	0.16	0.48	58	-10000	0	58
FOS	-0.009	0.007	0.001	139	-10000	0	139
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.068	0.085	0.2	123	-10000	0	123
STAT1/PIAS1	0.091	0.1	0.24	125	-10000	0	125
GRB2/SOS1/GAB family/SHP2/PI3K	0.019	0.03	0.23	4	-10000	0	4
STAT3 (dimer)	0.15	0.17	0.42	118	-10000	0	118
PRKCD	0.11	0.14	0.32	125	-10000	0	125
IL6R	0.008	0.015	0.033	44	-10000	0	44
SOCS3	-0.011	0.021	-10000	0	-10000	0	0
gp130 (dimer)/JAK1/JAK1/LMO4	0.033	0.041	0.09	121	-10000	0	121
Rac1/GTP	0.077	0.097	0.22	123	-10000	0	123
HCK	-0.011	0.006	0.001	93	-10000	0	93
MAPKKK cascade	0.05	0.061	0.25	13	-0.27	2	15
bone resorption	0.15	0.16	0.48	58	-10000	0	58
IRF1	0.16	0.18	0.5	85	-10000	0	85
mol:GDP	0.061	0.085	0.19	118	-10000	0	118
SOS1	0.001	0.004	0.021	10	-10000	0	10
VAV1	0.062	0.085	0.19	118	-10000	0	118
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.007	0.02	-10000	0	-0.22	3	3
PTPN11	0.031	0.035	0.25	1	-10000	0	1
IL6/IL6RA	0.017	0.026	0.055	96	-10000	0	96
gp130 (dimer)/TYK2/TYK2/LMO4	0.025	0.032	0.067	121	-10000	0	121
gp130 (dimer)/JAK2/JAK2/LMO4	0.025	0.032	0.067	123	-10000	0	123
IL6	0.012	0.02	0.042	101	-10000	0	101
PIAS3	-0.014	0.001	0	2	-10000	0	2
PTPRE	-0.031	0.022	-10000	0	-0.08	55	55
PIAS1	-0.014	0	-10000	0	-10000	0	0
RAC1	-0.004	0.013	0.013	185	-10000	0	185
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.034	0.05	0.11	122	-10000	0	122
LMO4	0.015	0.022	0.044	121	-10000	0	121
STAT3 (dimer)/PIAS3	0.14	0.16	0.39	117	-10000	0	117
MCL1	0.011	0.039	0.36	4	-10000	0	4

×

Syndecan-4-mediated signaling events

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
PTK2	0.017	0.059	0.11	68	-0.34	5	73
Syndecan-4/Syndesmos	0	0.057	0.13	1	-0.19	32	33
positive regulation of JNK cascade	-0.006	0.052	0.13	15	-0.19	25	40
Syndecan-4/ADAM12	0.016	0.076	0.14	68	-0.19	32	100
CCL5	-0.013	0.003	0	28	-10000	0	28
Rac1/GDP	-0.009	0	-10000	0	-10000	0	0
DNM2	-0.014	0	-10000	0	-10000	0	0
ITGA5	-0.012	0.005	0	74	-10000	0	74
SDCBP	-0.014	0	-10000	0	-10000	0	0
PLG	-0.017	0.007	-10000	0	-0.032	71	71
ADAM12	-0.014	0.001	0	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.015	0.013	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	0	0.057	0.13	1	-0.19	32	33
Syndecan-4/CXCL12/CXCR4	-0.006	0.054	0.13	15	-0.2	25	40
Syndecan-4/Laminin alpha3	0.014	0.075	0.14	66	-0.19	32	98
MDK	-0.006	0.007	0	299	-10000	0	299
Syndecan-4/FZD7	0	0.062	0.14	27	-0.19	30	57
Syndecan-4/Midkine	-0.002	0.056	0.14	24	-0.19	23	47
FZD7	-0.008	0.007	0	244	-10000	0	244
Syndecan-4/FGFR1/FGF	0.01	0.075	0.12	69	-0.19	31	100
THBS1	-0.013	0.004	0	43	-10000	0	43
integrin-mediated signaling pathway	-0.006	0.029	0.13	2	-0.21	4	6
positive regulation of MAPKKK cascade	-0.006	0.052	0.13	15	-0.19	25	40
Syndecan-4/TACI	0.016	0.076	0.14	69	-0.19	32	101
CXCR4	-0.007	0.007	0	275	-10000	0	275
cell adhesion	-0.01	0.006	-10000	0	-10000	0	0
Syndecan-4/Dynamin	0.016	0.076	0.14	69	-0.19	32	101
Syndecan-4/TSP1	0.01	0.072	0.14	51	-0.19	32	83
Syndecan-4/GIPC	0.016	0.076	0.14	69	-0.19	32	101
Syndecan-4/RANTES	0.012	0.073	0.14	58	-0.19	32	90
ITGB1	-0.014	0	-10000	0	-10000	0	0
LAMA1	0	0	-10000	0	-10000	0	0
LAMA3	-0.014	0.002	0	15	-10000	0	15
RAC1	-0.014	0	-10000	0	-10000	0	0
PRKCA	-0.013	0.012	-10000	0	-10000	0	0
Syndecan-4/alpha-Actinin	0.012	0.074	0.14	61	-0.19	32	93
TFPI	-0.011	0.006	0	117	-10000	0	117
F2	-0.005	0.015	0.016	168	-0.033	33	201
alpha5/beta1 Integrin	-0.015	0.006	0	74	-10000	0	74
positive regulation of cell adhesion	0.012	0.071	0.13	66	-0.19	32	98
ACTN1	-0.013	0.004	0	43	-10000	0	43
TNC	-0.001	0.003	0	504	-10000	0	504
Syndecan-4/CXCL12	0.014	0.073	0.14	61	-0.19	30	91
FGF6	-0.014	0	-10000	0	-10000	0	0
RHOA	-0.014	0.001	0	2	-10000	0	2
CXCL12	-0.014	0.002	0	15	-10000	0	15
TNFRSF13B	-0.014	0	-10000	0	-10000	0	0
FGF2	-0.014	0.001	0	2	-10000	0	2
FGFR1	-0.014	0.001	0	2	-10000	0	2
Syndecan-4/PI-4-5-P2	0	0.057	0.13	1	-0.19	32	33
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.011	0.006	0	104	-10000	0	104
cell migration	-0.008	0.007	-10000	0	-10000	0	0
PRKCD	-0.017	0.007	-10000	0	-0.032	71	71
vasculogenesis	0.009	0.07	0.13	51	-0.19	32	83
SDC4	0.023	0.071	0.14	69	-0.21	22	91
Syndecan-4/Tenascin C	-0.006	0.03	0.14	2	-0.22	4	6
Syndecan-4/PI-4-5-P2/PKC alpha	-0.012	0.011	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0.016	0.076	0.14	69	-0.19	32	101
MMP9	-0.01	0.008	0.016	2	-0.03	22	24
Rac1/GTP	-0.01	0.007	-10000	0	-10000	0	0
cytoskeleton organization	0	0.056	-10000	0	-0.18	32	32
GIPC1	-0.014	0	-10000	0	-10000	0	0
Syndecan-4/TFPI	0.009	0.067	0.14	48	-0.19	25	73

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.15	0.16	0.4	84	-10000	0	84
NCK1/PAK1/Dok-R	-0.009	0.016	-10000	0	-10000	0	0
NCK1/Dok-R	0.043	0.065	0.19	44	-10000	0	44
PIK3CA	-0.013	0.003	0	25	-10000	0	25
mol:beta2-estradiol	-0.016	0.035	-10000	0	-0.099	78	78
RELA	-0.014	0	-10000	0	-10000	0	0
SHC1	0.001	0.013	0.011	304	-10000	0	304
Rac/GDP	-0.009	0	-10000	0	-10000	0	0
F2	-0.047	0.052	-10000	0	-0.12	114	114
TNIP2	-0.014	0.002	0	11	-10000	0	11
NF kappa B/RelA	0.042	0.068	0.24	5	-10000	0	5
FN1	-0.011	0.006	0	104	-10000	0	104
PLD2	0.041	0.068	0.27	4	-10000	0	4
PTPN11	-0.014	0	-10000	0	-10000	0	0
GRB14	-0.014	0.003	0	18	-10000	0	18
ELK1	0.034	0.063	0.24	5	-10000	0	5
GRB7	-0.014	0.001	0	1	-10000	0	1
PAK1	-0.014	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	0.028	0.063	0.24	5	-10000	0	5
CDKN1A	0.17	0.18	0.46	92	-10000	0	92
ITGA5	-0.012	0.005	0	74	-10000	0	74
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.043	0.065	0.19	44	-10000	0	44
CRK	-0.014	0	-10000	0	-10000	0	0
mol:NO	0.14	0.15	0.37	86	-10000	0	86
PLG	0.041	0.068	0.24	8	-10000	0	8
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.11	0.13	0.34	65	-10000	0	65
GRB2	-0.014	0.001	0	5	-10000	0	5
PIK3R1	0.001	0.013	0.012	318	-10000	0	318
ANGPT2	0.18	0.17	0.33	279	-10000	0	279
BMX	0.041	0.068	0.24	8	-10000	0	8
ANGPT1	0.052	0.088	0.25	78	-10000	0	78
tube development	0.17	0.17	0.4	102	-10000	0	102
ANGPT4	0.006	0.019	0.024	288	-10000	0	288
response to hypoxia	0.006	0.008	0.025	39	-10000	0	39
Tie2/Ang1/GRB14	0.046	0.069	0.26	4	-10000	0	4
alpha5/beta1 Integrin	-0.015	0.006	0	74	-10000	0	74
FGF2	-0.023	0.008	-10000	0	-0.03	278	278
STAT5A (dimer)	0.18	0.19	0.48	87	-10000	0	87
mol:L-citrulline	0.14	0.15	0.37	86	-10000	0	86
AGTR1	0.014	0.026	0.037	293	-10000	0	293
MAPK14	0.1	0.1	0.33	17	-10000	0	17
Tie2/SHP2	0.025	0.037	0.15	4	-10000	0	4
TEK	0.03	0.042	0.19	4	-10000	0	4
RPS6KB1	0.13	0.14	0.37	81	-10000	0	81
Angiotensin II/AT1	0.038	0.044	0.079	279	-10000	0	279
Tie2/Ang1/GRB2	0.047	0.069	0.26	5	-10000	0	5
MAPK3	0.034	0.065	0.25	5	-10000	0	5
MAPK1	0.034	0.064	0.25	5	-10000	0	5
Tie2/Ang1/GRB7	0.047	0.07	0.26	5	-10000	0	5
NFKB1	-0.014	0.001	0	4	-10000	0	4
MAPK8	0.041	0.068	0.24	8	-10000	0	8
PI3K	0.14	0.15	0.39	81	-10000	0	81
FES	0.1	0.1	0.33	17	-10000	0	17
Crk/Dok-R	0.044	0.065	0.19	44	-10000	0	44
Tie2/Ang1/ABIN2	0.046	0.069	0.26	5	-10000	0	5
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.15	0.15	0.39	84	-10000	0	84
STAT5A	-0.011	0.01	0.018	55	-10000	0	55
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.13	0.14	0.37	81	-10000	0	81
Tie2/Ang2	0.18	0.18	0.46	84	-10000	0	84
Tie2/Ang1	0.05	0.073	0.22	44	-10000	0	44
FOXO1	0.16	0.16	0.42	84	-10000	0	84
ELF1	0.003	0.016	-10000	0	-10000	0	0
ELF2	0.048	0.071	0.21	44	-10000	0	44
mol:Choline	0.041	0.068	0.26	5	-10000	0	5
cell migration	-0.007	0.011	-10000	0	-10000	0	0
FYN	0.17	0.17	0.43	86	-10000	0	86
DOK2	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	0.17	0.18	0.45	93	-10000	0	93
ETS1	-0.001	0.043	0.1	78	-10000	0	78
PXN	0.12	0.14	0.35	82	-10000	0	82
ITGB1	-0.014	0	-10000	0	-10000	0	0
NOS3	0.14	0.15	0.38	84	-10000	0	84
RAC1	-0.014	0	-10000	0	-10000	0	0
TNF	0.016	0.041	0.11	78	-10000	0	78
MAPKKK cascade	0.041	0.068	0.26	5	-10000	0	5
RASA1	-0.014	0.002	0	8	-10000	0	8
Tie2/Ang1/Shc	0.05	0.073	0.26	9	-10000	0	9
NCK1	-0.014	0.002	0	11	-10000	0	11
vasculogenesis	0.13	0.14	0.34	100	-10000	0	100
mol:Phosphatidic acid	0.041	0.068	0.26	5	-10000	0	5
mol:Angiotensin II	0.016	0.015	0.03	279	-10000	0	279
mol:NADP	0.14	0.15	0.37	86	-10000	0	86
Rac1/GTP	0.06	0.095	-10000	0	-10000	0	0
MMP2	0.09	0.091	0.26	64	-10000	0	64

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.061	0.038	0.12	126	-0.046	3	129
GNAI2	-0.014	0.001	0	1	-10000	0	1
S1P/S1P5/G12	-0.007	0.001	0	4	-10000	0	4
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.001	0.004	0	481	-10000	0	481
RhoA/GTP	-0.062	0.039	0.048	3	-0.12	126	129
negative regulation of cAMP metabolic process	0	0.005	0.05	3	-0.068	1	4
GNAZ	-0.012	0.005	0	72	-10000	0	72
GNAI3	-0.012	0.005	0	65	-10000	0	65
GNA12	-0.014	0.001	0	4	-10000	0	4
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0	0.005	0.05	3	-0.069	1	4
RhoA/GDP	-0.009	0.001	0	2	-10000	0	2
RHOA	-0.014	0.001	0	2	-10000	0	2
GNAI1	-0.012	0.005	0	81	-10000	0	81

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.016	0.002	0	6	-10000	0	6
ER alpha/Gai/GDP/Gbeta gamma	-0.13	0.065	-10000	0	-0.16	406	406
AKT1	-0.019	0.013	-10000	0	-10000	0	0
PIK3CA	-0.014	0.003	0	25	-10000	0	25
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.018	0.014	-10000	0	-10000	0	0
mol:Ca2+	-0.016	0.008	-10000	0	-10000	0	0
IGF1R	-0.014	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.014	0	-10000	0	-10000	0	0
SHC1	-0.013	0.004	0	46	-10000	0	46
apoptosis	0.019	0.013	-10000	0	-10000	0	0
RhoA/GTP	-0.021	0.013	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.11	0.046	-10000	0	-0.12	422	422
regulation of stress fiber formation	0.002	0.024	-10000	0	-0.099	4	4
E2/ERA-ERB (dimer)	-0.014	0	-10000	0	-10000	0	0
KRAS	-0.014	0.002	0	9	-10000	0	9
G13/GTP	-0.012	0.001	0	2	-10000	0	2
pseudopodium formation	-0.002	0.024	0.099	4	-10000	0	4
E2/ER alpha (dimer)/PELP1	-0.014	0	-10000	0	-10000	0	0
GRB2	-0.014	0.001	0	5	-10000	0	5
GNG2	0	0	-10000	0	-10000	0	0
GNAO1	-0.001	0.004	0	481	-10000	0	481
HRAS	-0.014	0.001	0	2	-10000	0	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.079	0.039	-10000	0	-0.18	20	20
E2/ER beta (dimer)	-0.009	0	-10000	0	-10000	0	0
mol:GDP	-0.012	0.008	0.065	1	-10000	0	1
mol:NADP	-0.079	0.039	-10000	0	-0.18	20	20
PIK3R1	-0.013	0.004	0	36	-10000	0	36
mol:IP3	-0.017	0.008	-10000	0	-10000	0	0
IGF-1R heterotetramer	-0.014	0	-10000	0	-10000	0	0
PLCB1	-0.013	0.007	-10000	0	-10000	0	0
PLCB2	-0.013	0.007	-10000	0	-10000	0	0
IGF1	-0.014	0.001	0	4	-10000	0	4
mol:L-citrulline	-0.079	0.039	-10000	0	-0.18	20	20
RHOA	-0.014	0.001	0	2	-10000	0	2
Gai/GDP	-0.47	0.15	-10000	0	-0.52	481	481
JNK cascade	-0.009	0	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	-0.014	0	-10000	0	-10000	0	0
GNAQ	-0.014	0	-10000	0	-10000	0	0
ESR1	-0.014	0	-10000	0	-10000	0	0
Gq family/GDP/Gbeta gamma	-0.003	0.021	-10000	0	-0.18	6	6
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.025	0.061	-10000	0	-0.63	5	5
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.1	0.051	-10000	0	-0.13	343	343
GNAZ	-0.012	0.005	0	72	-10000	0	72
E2/ER alpha (dimer)	-0.009	0	-10000	0	-10000	0	0
STRN	-0.014	0	-10000	0	-10000	0	0
GNAL	-0.014	0	-10000	0	-10000	0	0
PELP1	-0.014	0	-10000	0	-10000	0	0
MAPK11	-0.014	0	-10000	0	-10000	0	0
GNAI2	-0.014	0.001	0	1	-10000	0	1
GNAI3	-0.012	0.005	0	65	-10000	0	65
GNAI1	-0.012	0.005	0	81	-10000	0	81
HBEGF	-0.086	0.074	0.12	5	-0.16	216	221
cAMP biosynthetic process	-0.015	0	-10000	0	-10000	0	0
SRC	-0.13	0.062	-10000	0	-0.16	406	406
PI3K	-0.015	0.005	0	60	-10000	0	60
GNB1	-0.014	0.002	0	6	-10000	0	6
G13/GDP/Gbeta gamma	-0.016	0.01	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.096	0.043	-10000	0	-0.12	391	391
Gs family/GTP	-0.016	0	-10000	0	-10000	0	0
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.013	0.008	0	143	-10000	0	143
vasodilation	-0.076	0.038	-10000	0	-0.16	31	31
mol:DAG	-0.017	0.008	-10000	0	-10000	0	0
Gs family/GDP/Gbeta gamma	-0.017	0.011	-10000	0	-10000	0	0
MSN	-0.002	0.025	0.1	4	-10000	0	4
Gq family/GTP	-0.009	0.001	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.018	0.014	-10000	0	-10000	0	0
NRAS	-0.011	0.006	0	136	-10000	0	136
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.076	0.038	0.16	31	-10000	0	31
GRB2/SOS1	-0.008	0.001	0	5	-10000	0	5
RhoA/GDP	-0.015	0.01	0.066	1	-10000	0	1
NOS3	-0.081	0.04	-10000	0	-0.19	20	20
GNA11	-0.014	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.054	0.04	-10000	0	-0.35	5	5
E2/ER alpha (dimer)/PELP1/Src	-0.11	0.048	-10000	0	-0.13	366	366
ruffle organization	-0.002	0.024	0.099	4	-10000	0	4
ROCK2	-0.004	0.046	0.12	6	-10000	0	6
GNA14	-0.014	0.001	0	2	-10000	0	2
GNA15	-0.014	0.002	0	7	-10000	0	7
GNA13	-0.014	0.001	0	2	-10000	0	2
MMP9	-0.096	0.077	0.11	3	-0.16	273	276
MMP2	-0.081	0.08	0.14	1	-0.16	223	224

×

PDGFR-beta 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
S1P1/Sphingosine-1-phosphate	0.022	0.052	0.11	125	-10000	0	125
PDGFB-D/PDGFRB/SLAP	-0.007	0.016	0.021	121	-10000	0	121
PDGFB-D/PDGFRB/APS/CBL	-0.005	0.014	0.019	138	-10000	0	138
AKT1	-0.026	0.032	0.15	4	-10000	0	4
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.019	0.043	0.11	50	-10000	0	50
PIK3CA	-0.014	0.003	0	25	-10000	0	25
FGR	0.012	0.029	0.14	3	-10000	0	3
mol:Ca2+	0.02	0.037	0.12	16	-10000	0	16
MYC	0.077	0.14	0.3	137	-10000	0	137
SHC1	-0.013	0.004	0	46	-10000	0	46
HRAS/GDP	-0.013	0.021	0.092	4	-10000	0	4
LRP1/PDGFRB/PDGFB	-0.008	0.02	0.025	134	-10000	0	134
GRB10	-0.014	0.002	0	16	-10000	0	16
PTPN11	-0.014	0	-10000	0	-10000	0	0
GO:0007205	0.02	0.037	0.12	16	-10000	0	16
PTEN	-0.014	0.001	0	2	-10000	0	2
GRB2	-0.014	0.001	0	5	-10000	0	5
GRB7	-0.014	0.001	0	1	-10000	0	1
PDGFB-D/PDGFRB/SHP2	-0.007	0.017	0.021	136	-10000	0	136
PDGFB-D/PDGFRB/GRB10	-0.007	0.017	0.021	131	-10000	0	131
cell cycle arrest	-0.007	0.016	0.021	121	-10000	0	121
HRAS	-0.014	0.001	0	2	-10000	0	2
HIF1A	-0.028	0.029	0.14	4	-10000	0	4
GAB1	0.036	0.06	0.13	129	-10000	0	129
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.031	0.061	0.13	130	-10000	0	130
PDGFB-D/PDGFRB	0.006	0.043	0.078	135	-10000	0	135
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.007	0.017	0.021	136	-10000	0	136
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.027	0.072	0.15	122	-10000	0	122
positive regulation of MAPKKK cascade	-0.007	0.017	0.021	136	-10000	0	136
PIK3R1	-0.013	0.004	0	36	-10000	0	36
mol:IP3	0.02	0.037	0.12	16	-10000	0	16
E5	0	0.001	-10000	0	-10000	0	0
CSK	-0.015	0.003	-10000	0	-0.023	2	2
PDGFB-D/PDGFRB/GRB7	-0.007	0.017	0.021	136	-10000	0	136
SHB	-0.014	0	-10000	0	-10000	0	0
BLK	0.009	0.025	0.15	2	-10000	0	2
PTPN2	-0.006	0.014	0.018	139	-10000	0	139
PDGFB-D/PDGFRB/SNX15	-0.007	0.017	0.021	136	-10000	0	136
BCAR1	0	0	-10000	0	-10000	0	0
VAV2	0.025	0.067	0.21	56	-10000	0	56
CBL	-0.014	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.007	0.017	0.021	136	-10000	0	136
LCK	0.01	0.026	0.15	2	-10000	0	2
PDGFRB	-0.005	0.015	0.021	136	-10000	0	136
ACP1	-0.014	0.001	0	2	-10000	0	2
HCK	0.009	0.027	0.15	2	-10000	0	2
ABL1	0.028	0.047	0.1	128	-10000	0	128
PDGFB-D/PDGFRB/CBL	0.038	0.057	0.15	59	-10000	0	59
PTPN1	-0.006	0.014	0.018	139	-10000	0	139
SNX15	-0.014	0	-10000	0	-10000	0	0
STAT3	-0.014	0.002	0	10	-10000	0	10
STAT1	-0.014	0.003	0	18	-10000	0	18
cell proliferation	0.076	0.13	0.3	137	-10000	0	137
SLA	-0.013	0.004	0	35	-10000	0	35
actin cytoskeleton reorganization	-0.015	0.027	0.1	12	-10000	0	12
SRC	0.009	0.025	0.15	2	-10000	0	2
PI3K	-0.03	0.013	0.013	2	-10000	0	2
PDGFB-D/PDGFRB/GRB7/SHC	-0.009	0.019	0.025	114	-10000	0	114
SH2B2	0	0	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.019	0.043	0.11	50	-10000	0	50
LYN	0.01	0.028	0.16	2	-10000	0	2
LRP1	-0.014	0.003	0	18	-10000	0	18
SOS1	0	0	-10000	0	-10000	0	0
STAT5B	-0.014	0	-10000	0	-10000	0	0
STAT5A	-0.014	0.001	0	1	-10000	0	1
NCK1-2/p130 Cas	-0.002	0.039	0.064	131	-10000	0	131
SPHK1	-0.008	0.011	0.011	144	-10000	0	144
EDG1	-0.008	0.012	0.012	139	-10000	0	139
mol:DAG	0.02	0.037	0.12	16	-10000	0	16
PLCG1	0.021	0.037	0.12	15	-10000	0	15
NHERF/PDGFRB	-0.009	0.02	0.025	134	-10000	0	134
YES1	0.008	0.026	0.17	2	-10000	0	2
cell migration	-0.009	0.019	0.025	134	-10000	0	134
SHC/Grb2/SOS1	-0.003	0.037	0.064	119	-10000	0	119
SLC9A3R2	-0.014	0	-10000	0	-10000	0	0
SLC9A3R1	-0.014	0.001	0	2	-10000	0	2
NHERF1-2/PDGFRB/PTEN	-0.01	0.023	0.029	133	-10000	0	133
FYN	0.004	0.042	0.15	2	-0.31	6	8
DOK1	-0.019	0.012	0.096	4	-10000	0	4
HRAS/GTP	-0.009	0.001	0	2	-10000	0	2
PDGFB	-0.014	0	-10000	0	-10000	0	0
RAC1	0.013	0.067	0.29	27	-10000	0	27
PRKCD	-0.013	0.019	0.1	4	-10000	0	4
FER	-0.013	0.019	0.1	4	-10000	0	4
MAPKKK cascade	-0.011	0.035	0.094	48	-10000	0	48
RASA1	-0.012	0.019	0.1	4	-10000	0	4
NCK1	-0.014	0.002	0	11	-10000	0	11
NCK2	-0.014	0.001	0	1	-10000	0	1
p62DOK/Csk	-0.026	0.009	0.081	4	-10000	0	4
PDGFB-D/PDGFRB/SHB	-0.007	0.017	0.021	136	-10000	0	136
chemotaxis	0.028	0.047	0.1	129	-10000	0	129
STAT1-3-5/STAT1-3-5	-0.012	0.036	0.052	124	-10000	0	124
Bovine Papilomavirus E5/PDGFRB	-0.001	0.012	0.018	134	-10000	0	134
PTPRJ	-0.014	0	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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.Total.Perturbations
PTK2	-0.015	0.002	0	6	-9999	6
CRKL	-0.014	0	-10000	0	-9999	0
Rac1/GDP	-0.009	0	-10000	0	-9999	0
DOCK1	-0.014	0	-10000	0	-9999	0
ITGA4	-0.014	0.001	0	5	-9999	5
alpha4/beta7 Integrin/MAdCAM1	-0.023	0.003	0	7	-9999	7
EPO	-0.014	0	-10000	0	-9999	0
alpha4/beta7 Integrin	-0.017	0.002	0	5	-9999	5
mol:GTP	0	0	-10000	0	-9999	0
CRK	-0.014	0	-10000	0	-9999	0
alpha4/beta1 Integrin	-0.017	0.002	0	5	-9999	5
EPO/EPOR (dimer)	-0.017	0	-10000	0	-9999	0
lamellipodium assembly	0.002	0.021	0.083	16	-9999	16
PIK3CA	-0.014	0.003	0	25	-9999	25
PI3K	-0.015	0.005	0	60	-9999	60
ARF6	-0.014	0	-10000	0	-9999	0
JAK2	-0.013	0.001	-10000	0	-9999	0
PXN	-0.014	0	-10000	0	-9999	0
PIK3R1	-0.013	0.004	0	36	-9999	36
MADCAM1	-0.014	0	-10000	0	-9999	0
cell adhesion	-0.023	0.003	0	7	-9999	7
CRKL/CBL	-0.017	0	-10000	0	-9999	0
ITGB1	-0.014	0	-10000	0	-9999	0
SRC	0.055	0.056	0.093	353	-9999	353
ITGB7	-0.014	0.001	0	2	-9999	2
RAC1	-0.014	0	-10000	0	-9999	0
alpha4/beta1 Integrin/VCAM1	-0.007	0.01	0	353	-9999	353
p130Cas/Crk/Dock1	0.049	0.056	0.088	353	-9999	353
VCAM1	-0.005	0.007	0	351	-9999	351
RHOA	-0.014	0.001	0	2	-9999	2
alpha4/beta1 Integrin/Paxillin/GIT1	-0.023	0.002	0	5	-9999	5
BCAR1	0.052	0.053	0.089	353	-9999	353
EPOR	-0.014	0	-10000	0	-9999	0
mol:GDP	0	0	-10000	0	-9999	0
CBL	-0.014	0	-10000	0	-9999	0
GIT1	-0.014	0	-10000	0	-9999	0
Rac1/GTP	0.002	0.022	0.083	16	-9999	16

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.005	0.049	0.12	67	-10000	0	67
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	-0.014	0	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.033	0.022	0.072	11	-10000	0	11
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.014	0.023	0.045	68	-10000	0	68
antigen processing and presentation of peptide antigen via MHC class I	-0.038	0.032	-10000	0	-10000	0	0
CaM/Ca2+	0.002	0.047	0.11	62	-10000	0	62
RAP1A	-0.014	0	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.007	0.053	0.12	69	-10000	0	69
AKT1	-0.009	0.044	0.089	58	-10000	0	58
MAP2K1	-0.015	0.038	0.076	65	-10000	0	65
MAP3K11	-0.01	0.041	0.084	81	-10000	0	81
IFNGR1	-0.012	0.012	0.018	68	-10000	0	68
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.1	0.096	-10000	0	-0.17	323	323
Rap1/GTP	-0.03	0.014	-10000	0	-10000	0	0
CRKL/C3G	-0.017	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.003	0.037	0.069	67	-10000	0	67
CEBPB	-0.016	0.062	0.21	2	-0.28	15	17
STAT3	-0.014	0.002	0	10	-10000	0	10
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.01	0.034	-10000	0	-10000	0	0
STAT1	-0.007	0.051	0.12	65	-10000	0	65
CALM1	-0.013	0.003	0	27	-10000	0	27
IFN-gamma (dimer)	-0.012	0.013	0.018	80	-10000	0	80
PIK3CA	-0.013	0.003	0	25	-10000	0	25
STAT1 (dimer)/PIAS1	-0.011	0.051	0.12	65	-10000	0	65
CEBPB/PTGES2/Cbp/p300	-0.037	0.037	-10000	0	-0.22	15	15
mol:Ca2+	0.004	0.047	0.11	67	-10000	0	67
MAPK3	-0.004	0.039	-10000	0	-10000	0	0
STAT1 (dimer)	-0.031	0.079	0.2	44	-10000	0	44
MAPK1	-0.025	0.12	-10000	0	-0.67	17	17
JAK2	-0.012	0.013	0.018	81	-10000	0	81
PIK3R1	-0.013	0.004	0	36	-10000	0	36
JAK1	-0.012	0.013	0.018	81	-10000	0	81
CAMK2D	0	0	-10000	0	-10000	0	0
DAPK1	-0.012	0.046	0.18	2	-0.19	15	17
SMAD7	0.02	0.086	0.14	165	-10000	0	165
CBL/CRKL/C3G	-0.017	0.044	0.084	81	-10000	0	81
PI3K	-0.002	0.045	0.098	57	-10000	0	57
IFNG	-0.012	0.013	0.018	80	-10000	0	80
apoptosis	-0.001	0.048	0.18	2	-10000	0	2
CAMK2G	-0.007	0.007	0	266	-10000	0	266
STAT3 (dimer)	-0.014	0.002	0	10	-10000	0	10
CAMK2A	-0.013	0.003	0	24	-10000	0	24
CAMK2B	-0.002	0.005	0	451	-10000	0	451
FRAP1	-0.011	0.046	0.1	33	-10000	0	33
PRKCD	-0.004	0.052	0.1	70	-10000	0	70
RAP1B	0	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.038	0.032	-10000	0	-10000	0	0
PTPN2	-0.014	0.001	0	1	-10000	0	1
EP300	-0.011	0.011	0.017	70	-10000	0	70
IRF1	-0.033	0.02	-10000	0	-10000	0	0
STAT1 (dimer)/PIASy	-0.01	0.052	0.13	58	-10000	0	58
SOCS1	-0.003	0.001	-10000	0	-10000	0	0
mol:GDP	-0.017	0.041	0.077	81	-10000	0	81
CASP1	-0.024	0.022	0.13	1	-10000	0	1
PTGES2	-0.014	0	-10000	0	-10000	0	0
IRF9	-0.012	0.037	0.078	57	-0.1	15	72
mol:PI-3-4-5-P3	-0.011	0.03	0.059	34	-10000	0	34
RAP1/GDP	-0.029	0.018	0.041	16	-10000	0	16
CBL	-0.01	0.041	0.084	81	-10000	0	81
MAP3K1	-0.01	0.041	0.085	77	-10000	0	77
PIAS1	-0.014	0	-10000	0	-10000	0	0
PIAS4	-0.014	0	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.038	0.032	-10000	0	-10000	0	0
PTPN11	-0.006	0.042	0.091	81	-10000	0	81
CREBBP	-0.011	0.011	0.017	70	-10000	0	70
RAPGEF1	-0.014	0	-10000	0	-10000	0	0

×

Class I PI3K 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
ARF5/GTP	0.001	0.043	0.075	131	-10000	0	131
DAPP1	0.012	0.041	0.1	66	-10000	0	66
Src family/SYK family/BLNK-LAT/BTK-ITK	0.027	0.059	0.16	60	-10000	0	60
mol:DAG	0.016	0.05	0.11	88	-10000	0	88
HRAS	-0.008	0.013	0.014	136	-10000	0	136
RAP1A	-0.008	0.013	0.014	137	-10000	0	137
ARF5/GDP	-0.007	0.047	-10000	0	-0.21	21	21
PLCG2	-0.014	0.002	0	10	-10000	0	10
PLCG1	-0.014	0	-10000	0	-10000	0	0
ARF5	-0.014	0	-10000	0	-10000	0	0
mol:GTP	0.004	0.042	0.075	135	-10000	0	135
ARF1/GTP	0.007	0.038	0.072	135	-10000	0	135
RHOA	-0.014	0.001	0	2	-10000	0	2
YES1	-0.012	0.005	0	79	-10000	0	79
RAP1A/GTP	0.006	0.045	0.082	135	-10000	0	135
ADAP1	0.003	0.039	0.07	131	-10000	0	131
ARAP3	0.004	0.042	0.074	135	-10000	0	135
INPPL1	-0.014	0	-10000	0	-10000	0	0
PREX1	0	0	-10000	0	-10000	0	0
ARHGEF6	-0.014	0.003	0	19	-10000	0	19
ARHGEF7	-0.014	0.001	0	1	-10000	0	1
ARF1	-0.014	0.001	0	2	-10000	0	2
NRAS	-0.012	0.007	0.014	1	-10000	0	1
FYN	-0.014	0.003	0	21	-10000	0	21
ARF6	-0.014	0	-10000	0	-10000	0	0
FGR	-0.014	0.003	0	17	-10000	0	17
mol:Ca2+	0.006	0.031	0.081	52	-10000	0	52
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.014	0.003	0	21	-10000	0	21
ZAP70	-0.014	0	-10000	0	-10000	0	0
mol:IP3	0.007	0.039	0.098	52	-10000	0	52
LYN	-0.012	0.005	0	64	-10000	0	64
ARF1/GDP	-0.007	0.047	-10000	0	-0.21	21	21
RhoA/GDP	0.002	0.045	0.079	127	-0.096	4	131
PDK1/Src/Hsp90	-0.02	0	-10000	0	-10000	0	0
BLNK	-0.012	0.005	0	68	-10000	0	68
actin cytoskeleton reorganization	0.001	0.038	0.098	7	-0.11	6	13
SRC	-0.014	0	-10000	0	-10000	0	0
PLEKHA2	-0.013	0.001	0	1	-10000	0	1
RAC1	-0.014	0	-10000	0	-10000	0	0
PTEN	-0.015	0.003	0	2	-0.025	4	6
HSP90AA1	-0.014	0	-10000	0	-10000	0	0
ARF6/GTP	0.001	0.043	0.075	131	-10000	0	131
RhoA/GTP	0.002	0.044	0.076	135	-10000	0	135
Src family/SYK family/BLNK-LAT	-0.002	0.021	-10000	0	-10000	0	0
BLK	-0.014	0	-10000	0	-10000	0	0
PDPK1	-0.014	0	-10000	0	-10000	0	0
CYTH1	0.003	0.039	0.07	131	-10000	0	131
HCK	-0.012	0.005	0	86	-10000	0	86
CYTH3	0.003	0.039	0.07	131	-10000	0	131
CYTH2	0.003	0.039	0.07	131	-10000	0	131
KRAS	-0.008	0.013	0.014	133	-10000	0	133
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.001	0.024	-10000	0	-10000	0	0
SGK1	0.006	0.025	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.004	0.047	-10000	0	-0.21	21	21
SOS1	0	0	-10000	0	-10000	0	0
SYK	-0.013	0.004	0	36	-10000	0	36
ARF6/GDP	0	0.042	0.072	127	-0.096	4	131
mol:PI-3-4-5-P3	0.004	0.042	0.076	131	-10000	0	131
ARAP3/RAP1A/GTP	0.006	0.045	0.083	135	-10000	0	135
VAV1	-0.014	0.001	0	1	-10000	0	1
mol:PI-3-4-P2	-0.009	0	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	-0.015	0.009	-10000	0	-10000	0	0
PLEKHA1	-0.012	0.004	0	63	-10000	0	63
Rac1/GDP	-0.007	0.047	-10000	0	-0.21	21	21
LAT	-0.014	0.001	0	1	-10000	0	1
Rac1/GTP	-0.009	0.046	-10000	0	-0.2	23	23
ITK	-0.001	0.04	0.068	128	-10000	0	128
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.017	0.058	0.12	87	-10000	0	87
LCK	-0.014	0.001	0	4	-10000	0	4
BTK	-0.001	0.04	0.068	131	-10000	0	131

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	-0.014	0.002	0	11	-10000	0	11
VLDLR	-0.014	0.001	0	3	-10000	0	3
LRPAP1	-0.014	0	-10000	0	-10000	0	0
NUDC	-0.014	0	-10000	0	-10000	0	0
RELN/LRP8	-0.009	0.01	0	282	-10000	0	282
CaM/Ca2+	-0.008	0.002	0	27	-10000	0	27
KATNA1	-0.014	0.002	0	6	-10000	0	6
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.011	0.013	0.092	2	-10000	0	2
IQGAP1/CaM	-0.012	0.008	0	145	-10000	0	145
DAB1	-0.014	0	-10000	0	-10000	0	0
IQGAP1	-0.011	0.006	0	127	-10000	0	127
PLA2G7	-0.014	0.002	0	8	-10000	0	8
CALM1	-0.013	0.003	0	27	-10000	0	27
DYNLT1	-0.012	0.005	0	75	-10000	0	75
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	-0.017	0	-10000	0	-10000	0	0
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	-0.014	0	-10000	0	-10000	0	0
CDK5R1	-0.011	0.006	0	101	-10000	0	101
LIS1/Poliovirus Protein 3A	-0.013	0.001	0	6	-10000	0	6
CDK5R2	-0.005	0.007	0	325	-10000	0	325
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.009	0.01	0	283	-10000	0	283
YWHAE	-0.014	0.001	0	2	-10000	0	2
NDEL1/14-3-3 E	-0.014	0.03	0.094	2	-10000	0	2
MAP1B	-0.002	0.001	-10000	0	-10000	0	0
RAC1	-0.006	0.003	0	133	-10000	0	133
p35/CDK5	-0.001	0.026	0.084	1	-10000	0	1
RELN	-0.007	0.007	0	282	-10000	0	282
PAFAH/LIS1	-0.02	0.003	0	14	-10000	0	14
LIS1/CLIP170	-0.02	0.002	0	6	-10000	0	6
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.023	0.028	0.046	1	-10000	0	1
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.005	0.006	-10000	0	-10000	0	0
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.002	0.016	0.075	1	-10000	0	1
LIS1/IQGAP1	-0.015	0.009	0	133	-10000	0	133
RHOA	-0.005	0.003	0	134	-10000	0	134
PAFAH1B1	-0.017	0.002	0	6	-10000	0	6
PAFAH1B3	-0.014	0.001	0	1	-10000	0	1
PAFAH1B2	-0.014	0	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	-0.018	0.01	-10000	0	-0.054	39	39
NDEL1/Katanin 60/Dynein heavy chain	-0.019	0.03	0.093	2	-10000	0	2
LRP8	-0.014	0	-10000	0	-10000	0	0
NDEL1/Katanin 60	-0.013	0.029	0.094	2	-10000	0	2
P39/CDK5	-0.002	0.018	0.084	1	-10000	0	1
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	-0.02	0.002	0	6	-10000	0	6
CDK5	-0.011	0.015	0.086	2	-10000	0	2
PPP2R5D	-0.014	0	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.016	0.002	0	6	-10000	0	6
CSNK2A1	-0.014	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.012	0.014	-10000	0	-10000	0	0
RELN/VLDLR	-0.011	0.012	0	283	-10000	0	283
CDC42	-0.006	0.003	0	133	-10000	0	133

×

IL23-mediated signaling events

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
CCL2	0.12	0.3	0.62	85	-0.79	15	100
IL23A	0.094	0.23	0.66	41	-10000	0	41
NF kappa B1 p50/RelA/I kappa B alpha	0.033	0.15	0.39	1	-10000	0	1
positive regulation of T cell mediated cytotoxicity	0.11	0.25	0.73	43	-10000	0	43
ITGA3	0.097	0.23	0.62	50	-10000	0	50
IL17F	0.056	0.17	0.39	75	-10000	0	75
IL12B	0.025	0.067	0.15	92	-10000	0	92
STAT1 (dimer)	0.086	0.21	0.59	42	-10000	0	42
CD4	0.1	0.24	0.67	46	-10000	0	46
IL23	0.085	0.22	0.6	41	-10000	0	41
IL23R	0.054	0.12	0.27	92	-10000	0	92
IL1B	0.099	0.24	0.67	44	-10000	0	44
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	0.099	0.23	0.66	40	-10000	0	40
TYK2	0.012	0.045	0.093	92	-10000	0	92
STAT4	-0.008	0.007	0	219	-10000	0	219
STAT3	-0.014	0.002	0	10	-10000	0	10
IL18RAP	-0.016	0.004	0.031	1	-0.033	1	2
IL12RB1	0.012	0.045	0.093	92	-10000	0	92
PIK3CA	-0.014	0.003	0	25	-10000	0	25
IL12Rbeta1/TYK2	0.013	0.051	0.1	92	-10000	0	92
IL23R/JAK2	0.069	0.14	0.33	92	-10000	0	92
positive regulation of chronic inflammatory response	0.11	0.25	0.73	43	-10000	0	43
natural killer cell activation	-0.004	0.009	-10000	0	-0.021	92	92
JAK2	0.025	0.067	0.15	92	-10000	0	92
PIK3R1	-0.013	0.004	0	36	-10000	0	36
NFKB1	-0.003	0.015	0.019	90	-10000	0	90
RELA	-0.003	0.015	0.019	92	-10000	0	92
positive regulation of dendritic cell antigen processing and presentation	0.085	0.21	0.58	44	-10000	0	44
ALOX12B	0.099	0.23	0.66	40	-10000	0	40
CXCL1	0.1	0.24	0.69	47	-10000	0	47
T cell proliferation	0.11	0.25	0.73	43	-10000	0	43
NFKBIA	-0.003	0.015	0.019	91	-10000	0	91
IL17A	0.056	0.17	0.37	86	-10000	0	86
PI3K	0.032	0.14	0.38	3	-10000	0	3
IFNG	0.009	0.022	0.08	28	-10000	0	28
STAT3 (dimer)	0.024	0.14	-10000	0	-10000	0	0
IL18R1	-0.016	0.004	0.031	1	-0.033	1	2
IL23/IL23R/JAK2/TYK2/SOCS3	0.083	0.19	0.43	92	-10000	0	92
IL18/IL18R	-0.02	0.013	0.14	1	-10000	0	1
macrophage activation	-0.001	0.007	-10000	0	-10000	0	0
TNF	0.098	0.23	0.67	41	-10000	0	41
STAT3/STAT4	0.026	0.13	0.38	2	-10000	0	2
STAT4 (dimer)	0.069	0.2	0.59	37	-10000	0	37
IL18	-0.014	0.005	0.031	1	-10000	0	1
IL19	0.099	0.22	0.66	40	-10000	0	40
STAT5A (dimer)	0.089	0.22	0.59	43	-10000	0	43
STAT1	-0.014	0.003	0	18	-10000	0	18
SOCS3	-0.014	0	-10000	0	-10000	0	0
CXCL9	0.11	0.24	0.64	58	-10000	0	58
MPO	0.099	0.22	0.66	40	-10000	0	40
positive regulation of humoral immune response	0.11	0.25	0.73	43	-10000	0	43
IL23/IL23R/JAK2/TYK2	0.11	0.25	0.73	43	-10000	0	43
IL6	0.1	0.24	0.66	54	-10000	0	54
STAT5A	-0.014	0.001	0	1	-10000	0	1
IL2	-0.018	0.01	0.066	1	-0.05	12	13
positive regulation of tyrosine phosphorylation of STAT protein	-0.004	0.009	-10000	0	-0.021	92	92
CD3E	0.099	0.23	0.66	40	-10000	0	40
keratinocyte proliferation	0.11	0.25	0.73	43	-10000	0	43
NOS2	0.1	0.22	0.64	43	-10000	0	43

×

Integrins in angiogenesis

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.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.008	0.008	0	292	-9999	292
alphaV beta3 Integrin	-0.02	0.004	0	18	-9999	18
PTK2	0.022	0.042	0.12	29	-9999	29
IGF1R	-0.014	0	-10000	0	-9999	0
PI4KB	-0.014	0.001	0	1	-9999	1
MFGE8	-0.014	0.001	0	3	-9999	3
SRC	-0.014	0	-10000	0	-9999	0
CDKN1B	-0.008	0.002	-10000	0	-9999	0
VEGFA	-0.006	0.007	0	287	-9999	287
ILK	-0.008	0.002	-10000	0	-9999	0
ROCK1	-0.014	0	-10000	0	-9999	0
AKT1	-0.012	0.01	0.099	4	-9999	4
PTK2B	0.041	0.064	0.094	298	-9999	298
alphaV/beta3 Integrin/JAM-A	-0.019	0.029	0.087	36	-9999	36
CBL	-0.014	0	-10000	0	-9999	0
mol:GTP	0	0	-10000	0	-9999	0
alphaV beta3 Integrin/ANGPTL3	-0.02	0.003	0	16	-9999	16
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.023	0.003	0	9	-9999	9
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.021	0.028	0.048	279	-9999	279
alphaV/beta3 Integrin/Syndecan-1	-0.018	0.006	0	59	-9999	59
PI4KA	-0.005	0.007	0	338	-9999	338
IGF-1R heterotetramer/IGF1/IRS1	-0.027	0.014	-10000	0	-9999	0
PI4 Kinase	-0.006	0.008	0	338	-9999	338
PIK3CA	-0.014	0.003	0	25	-9999	25
alphaV/beta3 Integrin/Osteopontin	-0.013	0.01	0	191	-9999	191
RPS6KB1	-0.013	0.051	0.18	12	-9999	12
TLN1	-0.013	0.004	0	46	-9999	46
MAPK3	-0.004	0.028	0.1	5	-9999	5
GPR124	-0.014	0.001	0	4	-9999	4
MAPK1	-0.004	0.027	0.1	5	-9999	5
PXN	-0.014	0	-10000	0	-9999	0
PIK3R1	-0.013	0.004	0	36	-9999	36
alphaV/beta3 Integrin/Tumstatin	-0.02	0.003	0	16	-9999	16
cell adhesion	-0.021	0.004	-10000	0	-9999	0
ANGPTL3	-0.014	0	-10000	0	-9999	0
VEGFR2 homodimer/VEGFA homodimer/Src	-0.009	0.01	0	292	-9999	292
IGF-1R heterotetramer	-0.014	0	-10000	0	-9999	0
Rac1/GDP	-0.009	0	-10000	0	-9999	0
TGFBR2	-0.014	0.002	0	8	-9999	8
ITGB3	-0.014	0	-10000	0	-9999	0
IGF1	-0.014	0.001	0	4	-9999	4
RAC1	-0.014	0	-10000	0	-9999	0
regulation of cell-matrix adhesion	-0.019	0.004	0	20	-9999	20
apoptosis	-0.014	0.002	0	16	-9999	16
CD47	-0.014	0.001	0	2	-9999	2
alphaV/beta3 Integrin/CD47	-0.02	0.004	0	18	-9999	18
VCL	-0.014	0	-10000	0	-9999	0
alphaV/beta3 Integrin/Del1	-0.02	0.003	0	16	-9999	16
CSF1	-0.014	0	-10000	0	-9999	0
PIK3C2A	-0.008	0.002	-10000	0	-9999	0
PI4 Kinase/Pyk2	-0.007	0.016	-10000	0	-9999	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.01	0.012	0	298	-9999	298
FAK1/Vinculin	0.02	0.041	0.12	29	-9999	29
alphaV beta3/Integrin/ppsTEM5	-0.019	0.004	0	20	-9999	20
RHOA	-0.014	0.001	0	2	-9999	2
VTN	-0.014	0.001	0	2	-9999	2
BCAR1	0	0	-10000	0	-9999	0
FGF2	-0.014	0.001	0	2	-9999	2
F11R	-0.016	0.004	0	36	-9999	36
alphaV/beta3 Integrin/Lactadherin	-0.02	0.004	0	19	-9999	19
alphaV/beta3 Integrin/TGFBR2	-0.019	0.004	0	24	-9999	24
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.017	0.003	0	16	-9999	16
HSP90AA1	-0.014	0	-10000	0	-9999	0
alphaV/beta3 Integrin/Talin	-0.016	0.006	0	57	-9999	57
mol:GDP	0	0	-10000	0	-9999	0
FN1	-0.011	0.006	0	104	-9999	104
alphaV/beta3 Integrin/Pyk2	0.034	0.058	0.09	271	-9999	271
SDC1	-0.013	0.004	0	47	-9999	47
VAV3	-0.018	0.017	0.091	12	-9999	12
PTPN11	-0.014	0	-10000	0	-9999	0
IRS1	-0.014	0.001	0	5	-9999	5
FAK1/Paxillin	0.02	0.041	0.12	29	-9999	29
cell migration	0.015	0.039	0.11	29	-9999	29
ITGAV	-0.014	0.002	0	16	-9999	16
PI3K	-0.027	0.02	0.073	12	-9999	12
SPP1	-0.009	0.007	0	187	-9999	187
KDR	-0.014	0.003	0	17	-9999	17
mol:PI-4-5-P2	0	0	-10000	0	-9999	0
alphaV/beta3 Integrin/Caspase 8	-0.014	0.002	0	16	-9999	16
COL4A3	-0.014	0	-10000	0	-9999	0
angiogenesis	-0.002	0.032	0.12	10	-9999	10
Rac1/GTP	-0.021	0.017	0.085	12	-9999	12
EDIL3	-0.014	0	-10000	0	-9999	0
cell proliferation	-0.019	0.004	0	24	-9999	24

×

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

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
MAP4K1	-0.046	0.096	0.15	9	-0.33	52	61
CRKL	-0.043	0.1	0.16	9	-0.34	52	61
HRAS	-0.04	0.084	0.15	9	-0.28	52	61
mol:PIP3	-0.03	0.097	0.16	9	-0.31	52	61
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	-0.014	0	-10000	0	-10000	0	0
GAB1	-0.039	0.11	0.18	9	-0.35	52	61
FOXO3	-0.034	0.092	-10000	0	-0.3	52	52
AKT1	-0.031	0.098	-10000	0	-0.32	52	52
BAD	-0.034	0.092	-10000	0	-0.3	52	52
megakaryocyte differentiation	-0.038	0.1	0.18	9	-0.34	52	61
GSK3B	-0.034	0.093	0.21	1	-0.3	52	53
RAF1	-0.035	0.073	0.13	9	-0.24	52	61
SHC1	-0.013	0.004	0	46	-10000	0	46
STAT3	-0.039	0.11	0.18	9	-0.35	52	61
STAT1	-0.074	0.21	-10000	0	-0.7	52	52
HRAS/SPRED1	-0.034	0.071	0.13	9	-0.24	52	61
cell proliferation	-0.039	0.1	0.18	9	-0.34	52	61
PIK3CA	-0.014	0.003	0	25	-10000	0	25
TEC	-0.014	0	-10000	0	-10000	0	0
RPS6KB1	-0.031	0.11	0.18	9	-0.34	52	61
HRAS/SPRED2	-0.034	0.074	0.13	9	-0.24	52	61
LYN/TEC/p62DOK	-0.044	0.1	0.17	9	-0.34	52	61
MAPK3	-0.028	0.055	0.12	1	-0.18	52	53
STAP1	-0.039	0.1	0.18	9	-0.35	52	61
GRAP2	-0.014	0	-10000	0	-10000	0	0
JAK2	-0.064	0.19	-10000	0	-0.62	52	52
STAT1 (dimer)	-0.073	0.21	-10000	0	-0.69	52	52
mol:Gleevec	0.002	0.004	0.014	52	-0.011	9	61
GRB2/SOCS1/VAV1	-0.047	0.1	0.17	9	-0.34	52	61
actin filament polymerization	-0.034	0.1	0.18	9	-0.34	52	61
LYN	-0.012	0.005	0	64	-10000	0	64
STAP1/STAT5A (dimer)	-0.055	0.14	-10000	0	-0.47	52	52
PIK3R1	-0.013	0.004	0	36	-10000	0	36
CBL/CRKL/GRB2	-0.048	0.095	0.16	9	-0.32	52	61
PI3K	-0.038	0.1	0.17	7	-0.33	52	59
PTEN	-0.014	0.001	0	2	-10000	0	2
SCF/KIT/EPO/EPOR	-0.087	0.24	-10000	0	-0.79	52	52
MAPK8	-0.04	0.11	0.18	9	-0.35	52	61
STAT3 (dimer)	-0.037	0.11	0.18	9	-0.34	52	61
positive regulation of transcription	-0.023	0.046	0.11	1	-0.15	52	53
mol:GDP	-0.043	0.087	0.15	9	-0.29	52	61
PIK3C2B	-0.039	0.11	0.18	9	-0.35	52	61
CBL/CRKL	-0.045	0.097	0.16	9	-0.33	52	61
FER	-0.04	0.11	0.18	9	-0.35	52	61
SH2B3	-0.039	0.1	0.18	9	-0.34	52	61
PDPK1	-0.032	0.091	0.15	9	-0.29	52	61
SNAI2	-0.034	0.1	0.19	9	-0.32	52	61
positive regulation of cell proliferation	-0.06	0.17	-10000	0	-0.57	52	52
KITLG	-0.016	0.012	0.035	9	-0.043	1	10
cell motility	-0.06	0.17	-10000	0	-0.57	52	52
PTPN6	-0.01	0.013	0.028	52	-10000	0	52
EPOR	-0.026	0.077	-10000	0	-10000	0	0
STAT5A (dimer)	-0.05	0.14	-10000	0	-0.48	52	52
SOCS1	-0.014	0	-10000	0	-10000	0	0
cell migration	0.039	0.1	0.34	52	-0.18	9	61
SOS1	0	0	-10000	0	-10000	0	0
EPO	-0.015	0.008	0.016	25	-10000	0	25
VAV1	-0.014	0.001	0	1	-10000	0	1
GRB10	-0.038	0.1	0.18	9	-0.34	52	61
PTPN11	-0.01	0.011	0.022	52	-10000	0	52
SCF/KIT	-0.036	0.11	0.2	9	-0.36	52	61
GO:0007205	0.003	0.006	0.02	52	-0.014	9	61
MAP2K1	-0.032	0.06	0.11	8	-0.2	52	60
CBL	-0.014	0	-10000	0	-10000	0	0
KIT	-0.081	0.25	0.31	9	-0.84	52	61
MAP2K2	-0.032	0.06	0.11	9	-0.2	52	61
SHC/Grb2/SOS1	-0.04	0.096	0.16	9	-0.32	52	61
STAT5A	-0.052	0.15	-10000	0	-0.49	52	52
GRB2	-0.014	0.001	0	5	-10000	0	5
response to radiation	-0.016	0.11	0.19	9	-0.32	52	61
SHC/GRAP2	-0.016	0.005	0	46	-10000	0	46
PTPRO	-0.039	0.1	0.18	9	-0.35	52	61
SH2B2	-0.035	0.11	0.18	9	-0.35	52	61
DOK1	-0.014	0	-10000	0	-10000	0	0
MATK	-0.04	0.11	0.18	9	-0.35	52	61
CREBBP	-0.023	0.034	0.14	9	-10000	0	9
BCL2	-0.025	0.075	-10000	0	-10000	0	0

×

Aurora B 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.002	0.005	0.05	2	-10000	0	2
STMN1	-0.015	0.004	0	28	-10000	0	28
Aurora B/RasGAP/Survivin	-0.011	0.012	-10000	0	-10000	0	0
Chromosomal passenger complex/Cul3 protein complex	-0.004	0.007	-10000	0	-0.065	6	6
BIRC5	-0.008	0.008	0.012	9	-10000	0	9
DES	0.005	0.005	-10000	0	-10000	0	0
Aurora C/Aurora B/INCENP	-0.002	0.018	0.025	21	-10000	0	21
Aurora B/TACC1	-0.006	0.011	0.014	71	-10000	0	71
Aurora B/PP2A	-0.01	0.012	0.014	99	-10000	0	99
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	-0.002	0.001	0.003	1	-0.007	1	2
mitotic metaphase/anaphase transition	0	0.001	-10000	0	-10000	0	0
NDC80	-0.011	0.008	0	184	-10000	0	184
Cul3 protein complex	-0.013	0.002	0	12	-10000	0	12
KIF2C	0	0.006	-10000	0	-10000	0	0
PEBP1	-0.006	0.013	0.014	161	-10000	0	161
KIF20A	-0.009	0.007	0.011	4	-10000	0	4
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	-0.01	0.012	0.014	99	-10000	0	99
SEPT1	0	0	-10000	0	-10000	0	0
SMC2	-0.013	0.005	0	61	-10000	0	61
SMC4	-0.003	0.006	0	401	-10000	0	401
NSUN2/NPM1/Nucleolin	0.006	0.018	-10000	0	-10000	0	0
PSMA3	-0.014	0.001	0	2	-10000	0	2
G2/M transition of mitotic cell cycle	0	0.001	0.004	1	-0.005	1	2
H3F3B	-0.004	0.002	0.003	22	-10000	0	22
AURKB	-0.008	0.01	0.011	103	-10000	0	103
AURKC	-0.014	0.001	0	2	-10000	0	2
CDCA8	-0.004	0.014	0.015	175	-10000	0	175
cytokinesis	0.002	0.024	0.062	47	-10000	0	47
Aurora B/Septin1	0.006	0.032	0.086	47	-10000	0	47
AURKA	-0.012	0.005	0.011	19	-10000	0	19
INCENP	-0.003	0.015	0.016	192	-10000	0	192
KLHL13	0	0	-10000	0	-10000	0	0
BUB1	-0.013	0.005	0.01	17	-10000	0	17
hSgo1/Aurora B/Survivin	-0.006	0.008	-10000	0	-10000	0	0
EVI5	-0.007	0.012	0.012	153	-10000	0	153
RhoA/GTP	-0.003	0.024	0.063	30	-10000	0	30
SGOL1	0	0	-10000	0	-10000	0	0
CENPA	0.004	0.017	0.086	11	-10000	0	11
NCAPG	-0.011	0.006	0	116	-10000	0	116
Aurora B/HC8 Proteasome	-0.01	0.012	0.014	99	-10000	0	99
NCAPD2	-0.011	0.006	0	105	-10000	0	105
Aurora B/PP1-gamma	-0.01	0.012	0.014	99	-10000	0	99
RHOA	-0.014	0.001	0	2	-10000	0	2
NCAPH	-0.014	0.002	0	16	-10000	0	16
NPM1	0	0.005	-10000	0	-10000	0	0
RASA1	-0.014	0.002	0	8	-10000	0	8
KLHL9	-0.014	0.002	0	12	-10000	0	12
mitotic prometaphase	0.001	0.003	0.007	93	-10000	0	93
proteasomal ubiquitin-dependent protein catabolic process	-0.01	0.012	0.014	99	-10000	0	99
PPP1CC	-0.014	0.001	0	1	-10000	0	1
Centraspindlin	-0.001	0.024	0.069	30	-10000	0	30
RhoA/GDP	-0.009	0.001	0	2	-10000	0	2
NSUN2	0	0.002	-10000	0	-10000	0	0
MYLK	-0.004	0.002	0.003	22	-10000	0	22
KIF23	-0.008	0.01	0.006	164	-10000	0	164
VIM	-0.014	0.005	0	47	-10000	0	47
RACGAP1	-0.009	0.008	0.001	179	-10000	0	179
mitosis	0	0	-10000	0	-10000	0	0
NCL	0	0.002	-10000	0	-10000	0	0
Chromosomal passenger complex	-0.001	0.01	0.047	9	-10000	0	9
Chromosomal passenger complex/EVI5	-0.014	0.016	-10000	0	-10000	0	0
TACC1	-0.014	0.001	0	3	-10000	0	3
PPP2R5D	-0.014	0	-10000	0	-10000	0	0
CUL3	-0.014	0	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

p75(NTR)-mediated 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
Sortilin/TRAF6	-0.017	0	-10000	0	-10000	0	0
Necdin/E2F1	-0.011	0.008	0	200	-10000	0	200
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.021	0.005	0	29	-10000	0	29
NGF (dimer)/p75(NTR)/BEX1	-0.009	0.006	0	175	-10000	0	175
NT-4/5 (dimer)/p75(NTR)	-0.008	0.002	0	22	-10000	0	22
IKBKB	-0.014	0	-10000	0	-10000	0	0
AKT1	-0.01	0.034	0.098	43	-10000	0	43
IKBKG	-0.014	0	-10000	0	-10000	0	0
BDNF	-0.004	0.006	0	376	-10000	0	376
MGDIs/NGR/p75(NTR)/LINGO1	-0.006	0.001	0	22	-10000	0	22
FURIN	-0.014	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.005	0.009	0	386	-10000	0	386
LINGO1	0	0	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	-0.035	0.011	-10000	0	-10000	0	0
proBDNF (dimer)	-0.004	0.006	0	376	-10000	0	376
NTRK1	-0.014	0.001	0	2	-10000	0	2
RTN4R	0	0	-10000	0	-10000	0	0
neuron apoptosis	0.009	0.029	0.14	10	-10000	0	10
IRAK1	-0.014	0.001	0	1	-10000	0	1
SHC1	-0.012	0.004	0	66	-10000	0	66
ARHGDIA	-0.014	0	-10000	0	-10000	0	0
RhoA/GTP	-0.009	0.001	0	2	-10000	0	2
Gamma Secretase	-0.025	0.007	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.016	0.006	0	61	-10000	0	61
MAGEH1	-0.013	0.004	0	41	-10000	0	41
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.011	0.009	0	215	-10000	0	215
Mammalian IAPs/DIABLO	-0.017	0.004	0	33	-10000	0	33
proNGF (dimer)	0	0	-10000	0	-10000	0	0
MAGED1	-0.014	0.001	0	3	-10000	0	3
APP	-0.014	0.001	0	1	-10000	0	1
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
ZNF274	-0.014	0.002	0	6	-10000	0	6
RhoA/GDP/RHOGDI	-0.012	0.022	0.091	22	-10000	0	22
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	-0.009	0.022	0.1	17	-10000	0	17
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.008	0.004	-10000	0	-10000	0	0
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.013	0.003	0	22	-10000	0	22
NCSTN	-0.013	0.003	0	30	-10000	0	30
mol:GTP	-0.012	0.004	0	67	-10000	0	67
PSENEN	-0.014	0.001	0	1	-10000	0	1
mol:ceramide	-0.013	0.023	0.096	22	-10000	0	22
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.007	0.002	-10000	0	-10000	0	0
p75(NTR)/beta APP	-0.016	0.003	0	23	-10000	0	23
BEX1	-0.01	0.007	0	158	-10000	0	158
mol:GDP	-0.006	0.001	0	22	-10000	0	22
NGF (dimer)	-0.015	0.006	0	78	-10000	0	78
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.011	0.002	0	22	-10000	0	22
PIK3R1	-0.013	0.004	0	36	-10000	0	36
RAC1/GTP	-0.01	0.002	0	22	-10000	0	22
MYD88	-0.012	0.005	0	71	-10000	0	71
CHUK	-0.014	0.001	0	1	-10000	0	1
NGF (dimer)/p75(NTR)/PKA	-0.012	0.004	0	67	-10000	0	67
RHOB	-0.014	0.003	0	21	-10000	0	21
RHOA	-0.014	0.001	0	2	-10000	0	2
MAGE-G1/E2F1	-0.009	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.014	0	-10000	0	-10000	0	0
TP53	-0.005	0.018	0.08	11	-10000	0	11
PRDM4	-0.013	0.023	0.097	22	-10000	0	22
BDNF (dimer)	-0.005	0.01	0	406	-10000	0	406
PIK3CA	-0.014	0.003	0	25	-10000	0	25
SORT1	-0.014	0	-10000	0	-10000	0	0
activation of caspase activity	-0.021	0.005	0	29	-10000	0	29
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.017	0.004	0	22	-10000	0	22
RHOC	-0.01	0.007	0	163	-10000	0	163
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	0.003	0.019	0.088	12	-10000	0	12
DIABLO	-0.014	0	-10000	0	-10000	0	0
SMPD2	-0.013	0.023	0.097	22	-10000	0	22
APH1B	-0.014	0	-10000	0	-10000	0	0
APH1A	-0.014	0.002	0	10	-10000	0	10
proNGF (dimer)/p75(NTR)/Sortilin	-0.013	0.003	0	22	-10000	0	22
PSEN1	-0.014	0.001	0	1	-10000	0	1
APAF-1/Pro-Caspase 9	-0.017	0.001	0	4	-10000	0	4
NT3 (dimer)/p75(NTR)	-0.016	0.003	0	22	-10000	0	22
MAPK8	0.004	0.023	0.089	15	-10000	0	15
MAPK9	0.004	0.023	0.089	15	-10000	0	15
APAF1	-0.014	0	-10000	0	-10000	0	0
NTF3	-0.014	0	-10000	0	-10000	0	0
NTF4	0	0	-10000	0	-10000	0	0
NDN	-0.009	0.007	0	200	-10000	0	200
RAC1/GDP	-0.009	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.015	0.012	-10000	0	-10000	0	0
p75 CTF/Sortilin/TRAF6/NRIF	-0.023	0.003	0	11	-10000	0	11
RhoA-B-C/GTP	-0.012	0.004	0	67	-10000	0	67
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.007	0.012	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.006	0.01	0	386	-10000	0	386
PRKACB	-0.013	0.004	0	46	-10000	0	46
proBDNF (dimer)/p75 ECD	-0.005	0.008	0	379	-10000	0	379
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.013	0.003	0	33	-10000	0	33
BIRC2	-0.014	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.005	0.015	0.087	10	-10000	0	10
BAD	-0.008	0.025	0.083	12	-10000	0	12
RIPK2	-0.014	0.001	0	1	-10000	0	1
NGFR	-0.014	0.003	0	22	-10000	0	22
CYCS	-0.017	0.022	0.091	22	-10000	0	22
ADAM17	-0.014	0.001	0	5	-10000	0	5
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.017	0.004	0	23	-10000	0	23
BCL2L11	-0.008	0.025	0.083	12	-10000	0	12
BDNF (dimer)/p75(NTR)	-0.005	0.008	0	386	-10000	0	386
PI3K	-0.015	0.006	0	79	-10000	0	79
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.011	0.002	0	22	-10000	0	22
NDNL2	0	0	-10000	0	-10000	0	0
YWHAE	-0.014	0.001	0	2	-10000	0	2
PRKCI	-0.014	0.001	0	1	-10000	0	1
NGF (dimer)/p75(NTR)	-0.008	0.002	0	22	-10000	0	22
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.017	0.004	0	25	-10000	0	25
TRAF6	-0.014	0	-10000	0	-10000	0	0
RAC1	-0.014	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
PLG	-0.014	0	-10000	0	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.003	0.014	0.082	9	-10000	0	9
SQSTM1	-0.014	0.001	0	1	-10000	0	1
NGFRAP1	-0.014	0.001	0	5	-10000	0	5
CASP3	-0.007	0.024	0.08	12	-10000	0	12
E2F1	-0.014	0	-10000	0	-10000	0	0
CASP9	-0.014	0.001	0	4	-10000	0	4
IKK complex	-0.023	0.014	0.042	24	-0.077	1	25
NGF (dimer)/TRKA	-0.009	0.001	0	2	-10000	0	2
MMP7	-0.012	0.005	0	78	-10000	0	78
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.021	0.005	0	28	-10000	0	28
MMP3	-0.014	0.002	0	7	-10000	0	7
APAF-1/Caspase 9	-0.035	0.013	-10000	0	-10000	0	0

×

Canonical 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
HDAC1	-0.02	0.014	-10000	0	-0.052	32	32
AES	-0.022	0.012	-10000	0	-0.047	43	43
FBXW11	-0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.001	-10000	0	-10000	0	0
LRP6/FZD1	-0.016	0.004	0.004	15	-10000	0	15
SMAD4	-0.011	0.006	0	126	-10000	0	126
DKK2	-0.014	0.002	0	10	-10000	0	10
TLE1	-0.022	0.012	-10000	0	-0.047	42	42
MACF1	-0.014	0.001	0	2	-10000	0	2
CTNNB1	0.034	0.024	0.12	9	-10000	0	9
WIF1	-0.002	0.005	0	462	-10000	0	462
beta catenin/RanBP3	-0.009	0.065	-10000	0	-0.2	7	7
KREMEN2	-0.014	0	-10000	0	-10000	0	0
DKK1	-0.011	0.006	0	116	-10000	0	116
beta catenin/beta TrCP1	0.036	0.024	0.11	10	-10000	0	10
FZD1	-0.013	0.002	0	10	-10000	0	10
AXIN2	0.028	0.039	0.11	44	-10000	0	44
AXIN1	-0.014	0	-10000	0	-10000	0	0
RAN	-0.015	0.001	0	3	-10000	0	3
Axin1/APC/GSK3/beta catenin	0.008	0.039	-10000	0	-0.43	4	4
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.021	0.029	0.11	1	-10000	0	1
Axin1/APC/GSK3	0.018	0.015	0.073	8	-10000	0	8
Axin1/APC/GSK3/beta catenin/Macf1	0.005	0.035	0.1	9	-0.14	18	27
HNF1A	-0.022	0.012	-10000	0	-0.048	42	42
CTBP1	-0.022	0.012	-10000	0	-0.048	42	42
MYC	0.09	0.14	0.33	137	-10000	0	137
RANBP3	-0.015	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.02	0.003	0	11	-10000	0	11
NKD1	0	0	-10000	0	-10000	0	0
TCF4	-0.022	0.012	-10000	0	-0.048	40	40
TCF3	-0.022	0.012	-10000	0	-0.048	42	42
WNT1/LRP6/FZD1/Axin1	-0.004	0.021	0.022	216	-10000	0	216
Ran/GTP	-0.009	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.088	0.13	-10000	0	-0.26	173	173
LEF1	-0.022	0.012	-10000	0	-0.048	42	42
DVL1	-0.001	0.004	-10000	0	-10000	0	0
CSNK2A1	-0.014	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.035	0.034	0.11	35	-0.16	1	36
DKK1/LRP6/Kremen 2	-0.016	0.008	0	117	-10000	0	117
LRP6	-0.014	0.001	0	1	-10000	0	1
CSNK1A1	-0.023	0.014	-10000	0	-0.052	43	43
NLK	-0.004	0.013	0.013	193	-10000	0	193
CCND1	0.072	0.13	0.34	99	-10000	0	99
WNT1	-0.014	0	-10000	0	-10000	0	0
GSK3A	-0.014	0	-10000	0	-10000	0	0
GSK3B	-0.013	0.004	0.008	15	-10000	0	15
FRAT1	-0.014	0.001	0	1	-10000	0	1
PPP2R5D	0	0.002	-10000	0	-10000	0	0
APC	-0.022	0.017	0.086	11	-10000	0	11
WNT1/LRP6/FZD1	-0.001	0.004	-10000	0	-10000	0	0
CREBBP	-0.022	0.012	-10000	0	-0.048	42	42

×

Circadian rhythm pathway

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
chromatin modification	0.004	0.067	0.24	2	-10000	0	2
CLOCK	-0.006	0.019	0.034	96	-10000	0	96
TIMELESS/CRY2	0.032	0.097	0.26	3	-10000	0	3
DEC1/BMAL1	-0.009	0.019	0.031	98	-10000	0	98
ATR	-0.014	0	-10000	0	-10000	0	0
NR1D1	0.024	0.072	-10000	0	-10000	0	0
ARNTL	-0.006	0.019	0.034	98	-10000	0	98
TIMELESS	0.048	0.12	0.3	98	-10000	0	98
NPAS2	-0.006	0.019	0.034	99	-10000	0	99
CRY2	-0.014	0	-10000	0	-10000	0	0
mol:CO	-0.017	0.04	-10000	0	-0.1	99	99
CHEK1	-0.013	0.005	0	61	-10000	0	61
mol:HEME	0.017	0.04	0.1	99	-10000	0	99
PER1	-0.014	0.001	0	3	-10000	0	3
BMAL/CLOCK/NPAS2	0.006	0.06	0.13	95	-10000	0	95
BMAL1/CLOCK	0.024	0.075	-10000	0	-10000	0	0
S phase of mitotic cell cycle	0.004	0.067	0.24	2	-10000	0	2
TIMELESS/CHEK1/ATR	0.004	0.068	0.24	2	-10000	0	2
mol:NADPH	0.017	0.04	0.1	99	-10000	0	99
PER1/TIMELESS	0.031	0.097	0.26	3	-10000	0	3
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	-0.014	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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.Total.Perturbations
NF kappa B/RelA	-0.013	0.01	-10000	0	-9999	0
Ran/GTP/Exportin 1/HDAC1	-0.016	0.006	0	68	-9999	68
NF kappa B1 p50/RelA/I kappa B alpha	0.011	0.037	0.062	184	-9999	184
SUMO1	-0.014	0	-10000	0	-9999	0
ZFPM1	0	0	-10000	0	-9999	0
NPC/RanGAP1/SUMO1/Ubc9	-0.005	0	-10000	0	-9999	0
FKBP3	-0.014	0.001	0	2	-9999	2
Histones	0.006	0.031	0.051	164	-9999	164
YY1/LSF	-0.011	0	-10000	0	-9999	0
SMG5	-0.014	0	-10000	0	-9999	0
RAN	-0.014	0.001	0	3	-9999	3
I kappa B alpha/HDAC3	-0.009	0.006	-10000	0	-9999	0
I kappa B alpha/HDAC1	0.008	0.03	0.052	165	-9999	165
SAP18	-0.014	0	-10000	0	-9999	0
RELA	0.019	0.034	0.066	185	-9999	185
HDAC1/Smad7	-0.018	0.007	0	65	-9999	65
RANGAP1	-0.014	0	-10000	0	-9999	0
HDAC3/TR2	0.009	0.032	0.052	185	-9999	185
NuRD/MBD3 Complex	0.006	0.021	0.041	137	-9999	137
NF kappa B1 p50/RelA	0.014	0.034	-10000	0	-9999	0
EntrezGene:23225	0	0	-10000	0	-9999	0
GATA2	-0.014	0.001	0	1	-9999	1
GATA1	-0.014	0	-10000	0	-9999	0
Mad/Max	-0.017	0	-10000	0	-9999	0
NuRD/MBD3 Complex/GATA1/Fog1	0.003	0.023	-10000	0	-9999	0
RBBP7	-0.014	0	-10000	0	-9999	0
NPC	-0.005	0	-10000	0	-9999	0
RBBP4	-0.012	0.006	0	100	-9999	100
MAX	-0.014	0	-10000	0	-9999	0
EntrezGene:9972	0	0	-10000	0	-9999	0
FBXW11	-0.014	0	-10000	0	-9999	0
NFKBIA	-0.006	0.004	0	186	-9999	186
KAT2B	0	0	-10000	0	-9999	0
mol:GTP	0	0	-10000	0	-9999	0
SIN3/HDAC complex	-0.006	0.005	0.048	2	-9999	2
SIN3 complex	-0.018	0	-10000	0	-9999	0
SMURF1	-0.014	0	-10000	0	-9999	0
CHD3	-0.014	0	-10000	0	-9999	0
SAP30	-0.014	0	-10000	0	-9999	0
EntrezGene:23636	0	0	-10000	0	-9999	0
NCOR1	-0.014	0	-10000	0	-9999	0
YY1/HDAC3	-0.007	0.005	-10000	0	-9999	0
YY1/HDAC2	-0.011	0.001	-10000	0	-9999	0
YY1/HDAC1	-0.009	0.004	-10000	0	-9999	0
NuRD/MBD2 Complex (MeCP1)	0.006	0.021	0.041	137	-9999	137
PPARG	0.021	0.04	0.075	184	-9999	184
HDAC8/hEST1B	-0.014	0	-10000	0	-9999	0
UBE2I	-0.014	0	-10000	0	-9999	0
beta TrCP1/SCF ubiquitin ligase complex	-0.014	0	-10000	0	-9999	0
TNFRSF1A	-0.009	0.007	0	183	-9999	183
HDAC3/SMRT (N-CoR2)	0.009	0.032	0.052	185	-9999	185
MBD3L2	0	0	-10000	0	-9999	0
ubiquitin-dependent protein catabolic process	-0.018	0.007	0	65	-9999	65
CREBBP	-0.014	0	-10000	0	-9999	0
NuRD/MBD3/MBD3L2 Complex	0.004	0.027	0.091	16	-9999	16
HDAC1	-0.012	0.005	0	65	-9999	65
HDAC3	-0.006	0.004	0	185	-9999	185
HDAC2	-0.014	0.001	0	5	-9999	5
YY1	-0.005	0	-10000	0	-9999	0
HDAC8	0	0	-10000	0	-9999	0
SMAD7	-0.014	0.001	0	1	-9999	1
NCOR2	-0.014	0	-10000	0	-9999	0
MXD1	-0.014	0	-10000	0	-9999	0
STAT3	-0.008	0.001	0	10	-9999	10
NFKB1	-0.014	0.001	0	4	-9999	4
EntrezGene:8021	0	0	-10000	0	-9999	0
RANBP2	-0.014	0.001	0	1	-9999	1
YY1/LSF/HDAC1	-0.013	0.005	-10000	0	-9999	0
YY1/SAP30/HDAC1	-0.013	0.005	-10000	0	-9999	0
EP300	-0.014	0	-10000	0	-9999	0
STAT3 (dimer non-phopshorylated)	-0.008	0.001	0	10	-9999	10
proteasomal ubiquitin-dependent protein catabolic process	-0.006	0.004	0	186	-9999	186
histone deacetylation	0.006	0.021	0.041	137	-9999	137
STAT3 (dimer non-phopshorylated)/HDAC3	0.007	0.027	0.046	175	-9999	175
nuclear export	0.013	0	-10000	0	-9999	0
PRKACA	-0.014	0	-10000	0	-9999	0
GATAD2B	0	0	-10000	0	-9999	0
GATAD2A	-0.013	0.004	0	49	-9999	49
GATA2/HDAC3	0.009	0.032	0.052	185	-9999	185
GATA1/HDAC1	-0.015	0.006	0	65	-9999	65
GATA1/HDAC3	0.009	0.032	0.052	185	-9999	185
CHD4	-0.014	0	-10000	0	-9999	0
TNF-alpha/TNFR1A	-0.011	0.008	0	185	-9999	185
SIN3/HDAC complex/Mad/Max	0.005	0.021	0.041	129	-9999	129
NuRD Complex	0.003	0.027	0.09	16	-9999	16
positive regulation of chromatin silencing	0.005	0.03	0.049	164	-9999	164
SIN3B	-0.014	0	-10000	0	-9999	0
MTA2	-0.014	0	-10000	0	-9999	0
SIN3A	0	0	-10000	0	-9999	0
XPO1	-0.014	0	-10000	0	-9999	0
SUMO1/HDAC1	-0.01	0.004	-10000	0	-9999	0
HDAC complex	-0.017	0.011	0	149	-9999	149
GATA1/Fog1	-0.009	0	-10000	0	-9999	0
FKBP25/HDAC1/HDAC2	-0.018	0.007	0	70	-9999	70
TNF	-0.014	0.001	0	2	-9999	2
negative regulation of cell growth	0.005	0.021	0.041	129	-9999	129
NuRD/MBD2/PRMT5 Complex	0.006	0.021	0.041	137	-9999	137
Ran/GTP/Exportin 1	-0.014	0.003	0.05	1	-9999	1
NF kappa B/RelA/I kappa B alpha	-0.007	0.005	-10000	0	-9999	0
SIN3/HDAC complex/NCoR1	-0.002	0.014	-10000	0	-9999	0
TFCP2	-0.014	0	-10000	0	-9999	0
NR2C1	-0.014	0	-10000	0	-9999	0
MBD3	-0.014	0	-10000	0	-9999	0
MBD2	-0.014	0	-10000	0	-9999	0

×

TCGA08_rtk_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
PDGFRA	-0.013	0.005	0	61	-10000	0	61
HRAS	-0.014	0.001	0	2	-10000	0	2
EGFR	-0.009	0.007	0	194	-10000	0	194
AKT	0.008	0.046	0.074	62	-0.1	3	65
FOXO3	-0.014	0	-10000	0	-10000	0	0
AKT1	-0.014	0.001	0	4	-10000	0	4
FOXO1	-0.014	0.002	0	11	-10000	0	11
AKT3	-0.014	0.001	0	1	-10000	0	1
FOXO4	-0.014	0	-10000	0	-10000	0	0
MET	-0.014	0.002	0	10	-10000	0	10
PIK3CA	-0.014	0.003	0	25	-10000	0	25
PIK3CB	-0.014	0	-10000	0	-10000	0	0
NRAS	-0.011	0.006	0	136	-10000	0	136
PIK3CG	-0.014	0	-10000	0	-10000	0	0
PIK3R3	-0.014	0.001	0	1	-10000	0	1
PIK3R2	-0.014	0	-10000	0	-10000	0	0
NF1	-0.014	0	-10000	0	-10000	0	0
RAS	0.023	0.03	0.049	274	-10000	0	274
ERBB2	-0.014	0	-10000	0	-10000	0	0
proliferation/survival/translation	-0.006	0.013	-10000	0	-10000	0	0
PI3K	0.024	0.032	0.059	204	-10000	0	204
PIK3R1	-0.013	0.004	0	36	-10000	0	36
KRAS	-0.014	0.002	0	9	-10000	0	9
FOXO	0.02	0.04	0.073	76	-10000	0	76
AKT2	-0.014	0	-10000	0	-10000	0	0
PTEN	-0.014	0.001	0	2	-10000	0	2

×

Regulation of Telomerase

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
Telomerase catalytic core complex	0.057	0.096	0.3	12	-10000	0	12
RAD9A	-0.014	0.001	0	1	-10000	0	1
AP1	-0.006	0.018	0.034	75	-10000	0	75
IFNAR2	-0.007	0.016	0.026	99	-10000	0	99
AKT1	0	0.017	0.036	97	-10000	0	97
ER alpha/Oestrogen	-0.004	0.01	0.017	99	-10000	0	99
NFX1/SIN3/HDAC complex	0.013	0.03	0.054	146	-10000	0	146
EGF	-0.009	0.012	0.016	99	-10000	0	99
SMG5	-0.014	0	-10000	0	-10000	0	0
SMG6	-0.014	0	-10000	0	-10000	0	0
SP3/HDAC2	-0.007	0.021	0.044	71	-10000	0	71
TERT/c-Abl	0.026	0.056	0.27	12	-10000	0	12
SAP18	-0.009	0.01	0.011	99	-10000	0	99
MRN complex	-0.02	0	-10000	0	-10000	0	0
WT1	-0.007	0.016	0.026	96	-10000	0	96
WRN	-0.014	0.001	0	5	-10000	0	5
SP1	-0.006	0.019	0.035	99	-10000	0	99
SP3	-0.008	0.011	0.017	72	-10000	0	72
TERF2IP	-0.013	0.004	0	44	-10000	0	44
Telomerase/Nucleolin	0.008	0.029	-10000	0	-10000	0	0
Mad/Max	-0.008	0.02	0.034	99	-10000	0	99
TERT	0.035	0.078	0.3	17	-10000	0	17
CCND1	0.07	0.13	0.33	82	-10000	0	82
MAX	-0.009	0.012	0.017	99	-10000	0	99
RBBP7	-0.009	0.01	0.012	99	-10000	0	99
RBBP4	-0.008	0.01	0.005	173	-10000	0	173
TERF2	-0.015	0.006	-10000	0	-10000	0	0
PTGES3	-0.014	0.001	0	1	-10000	0	1
SIN3A	0.001	0.001	-10000	0	-10000	0	0
Telomerase/911	0.012	0.027	0.12	4	-10000	0	4
CDKN1B	-0.007	0.042	0.099	71	-10000	0	71
RAD1	-0.014	0.001	0	2	-10000	0	2
XRCC5	-0.014	0	-10000	0	-10000	0	0
XRCC6	-0.014	0	-10000	0	-10000	0	0
SAP30	-0.009	0.01	0.012	99	-10000	0	99
TRF2/PARP2	-0.017	0.006	-10000	0	-10000	0	0
UBE3A	-0.009	0.012	0.016	99	-10000	0	99
JUN	-0.008	0.012	0.017	99	-10000	0	99
E6	0.001	0.003	0.008	99	-10000	0	99
HPV-16 E6/E6AP	-0.002	0.013	0.025	99	-10000	0	99
FOS	-0.007	0.011	0.017	75	-10000	0	75
IFN-gamma/IRF1	-0.012	0.022	0.035	87	-10000	0	87
PARP2	-0.014	0.001	0	3	-10000	0	3
BLM	-0.011	0.006	0	124	-10000	0	124
Telomerase	0.012	0.028	0.11	3	-10000	0	3
IRF1	-0.011	0.014	0.016	87	-10000	0	87
ESR1	-0.009	0.011	0.013	99	-10000	0	99
KU/TER	-0.017	0	-10000	0	-10000	0	0
ATM/TRF2	-0.015	0.006	0	76	-10000	0	76
ubiquitin-dependent protein catabolic process	0.011	0.031	0.081	48	-10000	0	48
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.009	0.028	0.078	34	-10000	0	34
HDAC1	-0.008	0.01	0.006	150	-10000	0	150
HDAC2	-0.006	0.017	0.031	95	-10000	0	95
ATM	0.007	0.009	0.035	51	-10000	0	51
SMAD3	-0.018	0.006	0	27	-0.03	4	31
ABL1	-0.014	0.001	0	4	-10000	0	4
MXD1	-0.009	0.012	0.017	99	-10000	0	99
MRE11A	-0.014	0	-10000	0	-10000	0	0
HUS1	-0.014	0	-10000	0	-10000	0	0
RPS6KB1	-0.014	0.001	0	1	-10000	0	1
TERT/NF kappa B1/14-3-3	0.05	0.085	0.28	3	-10000	0	3
NR2F2	-0.017	0.007	-10000	0	-0.033	2	2
MAPK3	-0.012	0.012	0.012	99	-10000	0	99
MAPK1	-0.011	0.012	0.012	99	-10000	0	99
TGFB1/TGF beta receptor Type II	-0.015	0.004	-10000	0	-10000	0	0
NFKB1	-0.014	0.001	0	4	-10000	0	4
HNRNPC	-0.014	0	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.007	0.009	0.035	51	-10000	0	51
NBN	-0.014	0	-10000	0	-10000	0	0
EGFR	-0.005	0.011	0.015	74	-10000	0	74
mol:Oestrogen	0.001	0.002	0.005	2	-10000	0	2
EGF/EGFR	-0.005	0.016	0.029	74	-10000	0	74
MYC	-0.007	0.011	0.019	56	-10000	0	56
IL2	-0.006	0.019	0.035	99	-10000	0	99
KU	-0.017	0	-10000	0	-10000	0	0
RAD50	-0.014	0	-10000	0	-10000	0	0
HSP90AA1	-0.014	0	-10000	0	-10000	0	0
TGFB1	-0.015	0.004	-10000	0	-10000	0	0
TRF2/BLM	-0.013	0.009	-10000	0	-10000	0	0
FRAP1	-0.014	0.001	0	1	-10000	0	1
KU/TERT	0.055	0.088	0.28	10	-10000	0	10
SP1/HDAC2	-0.003	0.031	0.064	95	-10000	0	95
PINX1	0	0	-10000	0	-10000	0	0
Telomerase/EST1A	0.008	0.029	-10000	0	-10000	0	0
Smad3/Myc	-0.015	0.01	-10000	0	-10000	0	0
911 complex	-0.02	0.002	0	3	-10000	0	3
IFNG	-0.013	0.014	0.016	99	-10000	0	99
Telomerase/PinX1	0.008	0.026	-10000	0	-10000	0	0
Telomerase/AKT1/mTOR/p70S6K	0.019	0.042	0.14	9	-10000	0	9
SIN3B	-0.009	0.01	0.012	99	-10000	0	99
YWHAE	-0.014	0.001	0	2	-10000	0	2
Telomerase/EST1B	0.008	0.029	-10000	0	-10000	0	0
response to DNA damage stimulus	0.003	0.009	0.044	25	-10000	0	25
MRN complex/TRF2/Rap1	-0.026	0.01	-10000	0	-10000	0	0
TRF2/WRN	-0.017	0.006	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	0.008	0.029	-10000	0	-10000	0	0
E2F1	-0.007	0.016	0.026	99	-10000	0	99
ZNFX1	0.001	0.001	-10000	0	-10000	0	0
PIF1	0	0	-10000	0	-10000	0	0
NCL	-0.014	0	-10000	0	-10000	0	0
DKC1	-0.014	0.002	0	7	-10000	0	7
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Wnt 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.Total.Perturbations
Noncanonical Wnts/FZD	-0.006	0.005	-9999	0	-9999	0
FZD6	-0.012	0.006	0	100	-9999	100
WNT6	-0.014	0	-9999	0	-9999	0
WNT4	-0.014	0.001	0	2	-9999	2
FZD3	-0.014	0.002	0	16	-9999	16
WNT5A	-0.01	0.007	0	168	-9999	168
WNT11	-0.014	0.001	0	2	-9999	2

×

S1P4 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	-0.001	0.004	0	481	-10000	0	481
CDC42/GTP	-0.062	0.039	0.048	3	-0.12	127	130
PLCG1	-0.001	0.006	0.043	3	-0.069	1	4
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	-0.014	0.001	0	1	-10000	0	1
GNAI3	-0.012	0.005	0	65	-10000	0	65
G12/G13	-0.017	0.002	0	6	-10000	0	6
cell migration	-0.062	0.038	0.046	3	-0.12	127	130
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
MAPK3	-0.001	0.006	0.043	3	-0.069	1	4
MAPK1	-0.001	0.006	0.043	3	-0.069	1	4
S1P/S1P5/Gi	0	0.005	0.05	3	-0.069	1	4
GNAI1	-0.012	0.005	0	81	-10000	0	81
CDC42/GDP	-0.009	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.007	0.001	0	4	-10000	0	4
RHOA	-0.015	0.012	0.095	6	-10000	0	6
S1P/S1P4/Gi	0	0.005	0.05	3	-0.069	1	4
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	-0.012	0.005	0	72	-10000	0	72
S1P/S1P4/G12/G13	-0.012	0.001	0	6	-10000	0	6
GNA12	-0.014	0.001	0	4	-10000	0	4
GNA13	-0.014	0.001	0	2	-10000	0	2
CDC42	-0.014	0	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.005	0.003	-10000	0	-10000	0	0
HDAC1	-0.02	0.015	-10000	0	-0.059	32	32
AES	-0.016	0.003	-10000	0	-10000	0	0
FBXW11	-0.014	0	-10000	0	-10000	0	0
DTX1	0	0	-10000	0	-10000	0	0
LRP6/FZD1	-0.016	0.002	0	11	-10000	0	11
TLE1	-0.017	0.004	-10000	0	-0.029	11	11
AP1	-0.005	0.004	-10000	0	-10000	0	0
NCSTN	-0.013	0.003	0	30	-10000	0	30
ADAM10	-0.014	0.003	0	18	-10000	0	18
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.047	0.07	0.22	43	-10000	0	43
NICD/RBPSUH	-0.004	0.014	-10000	0	-10000	0	0
WIF1	-0.002	0.005	0	462	-10000	0	462
NOTCH1	-0.003	0.001	-10000	0	-10000	0	0
PSENEN	-0.014	0.001	0	1	-10000	0	1
KREMEN2	-0.014	0	-10000	0	-10000	0	0
DKK1	-0.011	0.006	0	116	-10000	0	116
beta catenin/beta TrCP1	0.014	0.031	0.1	8	-10000	0	8
APH1B	-0.014	0	-10000	0	-10000	0	0
APH1A	-0.014	0.002	0	10	-10000	0	10
AXIN1	0.009	0.018	0.18	4	-0.15	1	5
CtBP/CBP/TCF1/TLE1/AES	-0.043	0.053	-10000	0	-0.12	170	170
PSEN1	-0.014	0.001	0	1	-10000	0	1
FOS	-0.011	0.006	0	127	-10000	0	127
JUN	-0.014	0.001	0	1	-10000	0	1
MAP3K7	-0.019	0.007	-10000	0	-0.036	43	43
CTNNB1	0.016	0.028	0.11	8	-10000	0	8
MAPK3	-0.014	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.02	0.003	0	11	-10000	0	11
HNF1A	-0.016	0.003	-10000	0	-10000	0	0
CTBP1	-0.016	0.004	-10000	0	-10000	0	0
MYC	0.084	0.14	0.32	135	-10000	0	135
NKD1	-0.002	0.002	-10000	0	-0.008	43	43
FZD1	-0.014	0.002	0	10	-10000	0	10
NOTCH1 precursor/Deltex homolog 1	-0.003	0.001	-10000	0	-10000	0	0
apoptosis	-0.005	0.004	-10000	0	-10000	0	0
Delta 1/NOTCHprecursor	-0.003	0.001	-10000	0	-10000	0	0
DLL1	0	0	-10000	0	-10000	0	0
PPARD	0.014	0.03	-10000	0	-10000	0	0
Gamma Secretase	-0.007	0.026	0.03	169	-10000	0	169
APC	-0.006	0.063	0.18	1	-0.28	25	26
DVL1	0.001	0.006	0.022	39	-10000	0	39
CSNK2A1	-0.011	0.008	0.014	43	-10000	0	43
MAP3K7IP1	-0.019	0.007	-10000	0	-0.036	43	43
DKK1/LRP6/Kremen 2	-0.016	0.008	0	117	-10000	0	117
LRP6	-0.014	0.001	0	1	-10000	0	1
CSNK1A1	-0.011	0.008	0.014	43	-10000	0	43
NLK	-0.018	0.016	-10000	0	-0.037	190	190
CCND1	0.065	0.13	0.33	99	-10000	0	99
WNT1	-0.014	0	-10000	0	-10000	0	0
Axin1/APC/beta catenin	0.013	0.038	0.14	6	-10000	0	6
DKK2	-0.014	0.002	0	10	-10000	0	10
NOTCH1 precursor/DVL1	0.005	0.009	-10000	0	-10000	0	0
GSK3B	-0.015	0.001	0	4	-10000	0	4
FRAT1	-0.016	0.003	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.005	0.003	-10000	0	-10000	0	0
PPP2R5D	0.008	0.008	-10000	0	-10000	0	0
MAPK1	-0.014	0.003	0	17	-10000	0	17
WNT1/LRP6/FZD1	-0.001	0.008	0.026	19	-10000	0	19
RBPJ	-0.014	0	-10000	0	-10000	0	0
CREBBP	0.002	0.023	0.031	193	-10000	0	193

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.009	0.001	-9999	0	-10000	0	0
TRAF2/ASK1	-0.013	0.001	0	4	-10000	0	4
ATM	-0.014	0.003	0	25	-10000	0	25
MAP2K3	0	0.012	-9999	0	-10000	0	0
response to stress	0	0	-9999	0	-10000	0	0
MAP2K6	0	0.014	-9999	0	-10000	0	0
hyperosmotic response	0	0	-9999	0	-10000	0	0
response to oxidative stress	0	0	-9999	0	-10000	0	0
GADD45G	-0.014	0.002	0	13	-10000	0	13
TXN	-0.003	0	0	1	-10000	0	1
CALM1	-0.013	0.003	0	27	-10000	0	27
GADD45A	-0.013	0.004	0	46	-10000	0	46
GADD45B	-0.014	0.002	0	9	-10000	0	9
MAP3K1	-0.014	0.001	0	1	-10000	0	1
MAP3K6	-0.014	0.001	0	3	-10000	0	3
MAP3K7	-0.014	0.001	0	1	-10000	0	1
MAP3K4	-0.014	0.001	0	1	-10000	0	1
mol:Ca2+	0	0	-9999	0	-10000	0	0
ASK1/ASK2	-0.017	0.002	0	7	-10000	0	7
TAK1/TAB family	0.003	0	-9999	0	-10000	0	0
RAC1/OSM/MEKK3	-0.012	0	-9999	0	-10000	0	0
TRAF2	-0.014	0	-9999	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.007	0.012	-9999	0	-10000	0	0
TRAF6	-0.005	0	-9999	0	-10000	0	0
RAC1	-0.014	0	-9999	0	-10000	0	0
mol:LPS	0	0	-9999	0	-10000	0	0
CAMK2B	-0.002	0.005	0	451	-10000	0	451
CCM2	0	0	-9999	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.002	0.005	0	451	-10000	0	451
MAPK11	-0.014	0	-9999	0	-10000	0	0
response to DNA damage stimulus	0	0	-9999	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.003	0.006	0	451	-10000	0	451
OSM/MEKK3	-0.009	0	-9999	0	-10000	0	0
TAOK1	-0.003	0.001	0	25	-10000	0	25
TAOK2	-0.005	0.001	0	25	-10000	0	25
TAOK3	-0.005	0.001	0	25	-10000	0	25
MAP3K7IP1	-0.014	0	-9999	0	-10000	0	0
MAPK14	-0.014	0.001	0	2	-10000	0	2
MAP3K7IP2	-0.014	0	-9999	0	-10000	0	0
MAP3K5	-0.014	0.001	0	4	-10000	0	4
MAP3K10	-0.014	0	-9999	0	-10000	0	0
MAP3K3	-0.014	0	-9999	0	-10000	0	0
TRX/ASK1	-0.009	0.003	-9999	0	-0.065	1	1
GADD45/MTK1/MTK1	-0.019	0.007	0	67	-10000	0	67

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.02	0.003	0	12	-9999	0	12
fibroblast growth factor receptor signaling pathway	-0.02	0.003	0	12	-9999	0	12
LAMA1	0	0	-10000	0	-9999	0	0
PRNP	-0.013	0.003	0	33	-9999	0	33
GPC1/SLIT2	-0.011	0.008	0	189	-9999	0	189
SMAD2	-0.02	0.02	0.092	16	-9999	0	16
GPC1/PrPc/Cu2+	-0.012	0.004	0	41	-9999	0	41
GPC1/Laminin alpha1	-0.008	0.001	0	8	-9999	0	8
TDGF1	-0.014	0.001	0	2	-9999	0	2
CRIPTO/GPC1	-0.017	0.002	0	10	-9999	0	10
APP/GPC1	-0.017	0.002	0	9	-9999	0	9
mol:NO	0	0	-10000	0	-9999	0	0
YES1	-0.016	0.014	0.099	6	-9999	0	6
FLT1	-0.014	0	-10000	0	-9999	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.02	0.003	0	16	-9999	0	16
SERPINC1	-0.014	0.001	0	1	-9999	0	1
FYN	-0.017	0.017	0.099	10	-9999	0	10
FGR	-0.017	0.017	0.099	10	-9999	0	10
positive regulation of MAPKKK cascade	0.007	0.046	0.1	74	-9999	0	74
SLIT2	-0.009	0.007	0	186	-9999	0	186
GPC1/NRG	-0.017	0.002	0	8	-9999	0	8
NRG1	-0.014	0	-10000	0	-9999	0	0
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.009	0.01	0	290	-9999	0	290
LYN	-0.016	0.017	0.099	9	-9999	0	9
mol:Spermine	-0.008	0.001	0	8	-9999	0	8
cell growth	-0.02	0.003	0	12	-9999	0	12
BMP signaling pathway	0.014	0.002	-10000	0	0	8	8
SRC	-0.018	0.016	0.099	10	-9999	0	10
TGFBR1	-0.014	0	-10000	0	-9999	0	0
mol:Cu2+	0	0	-10000	0	-9999	0	0
PLA2G2A	-0.009	0.007	0	191	-9999	0	191
GPC1	-0.014	0.002	0	8	-9999	0	8
TGFBR1 (dimer)	-0.014	0	-10000	0	-9999	0	0
VEGFA	-0.006	0.007	0	287	-9999	0	287
BLK	-0.018	0.016	0.099	10	-9999	0	10
HCK	-0.015	0.017	0.099	9	-9999	0	9
FGF2	-0.014	0.001	0	2	-9999	0	2
FGFR1	-0.014	0.001	0	2	-9999	0	2
VEGFR1 homodimer	-0.014	0	-10000	0	-9999	0	0
TGFBR2	-0.014	0.002	0	8	-9999	0	8
cell death	-0.017	0.002	0	9	-9999	0	9
ATIII/GPC1	-0.017	0.002	0	9	-9999	0	9
PLA2G2A/GPC1	-0.011	0.008	0	196	-9999	0	196
LCK	-0.018	0.016	0.099	9	-9999	0	9
neuron differentiation	-0.017	0.002	0	8	-9999	0	8
PrPc/Cu2+	-0.008	0.002	0	33	-9999	0	33
APP	-0.014	0.001	0	1	-9999	0	1
TGFBR2 (dimer)	-0.014	0.002	0	8	-9999	0	8

×

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	0.015	0.045	0.14	39	-10000	0	39
IKBKB	0.019	0.038	0.15	23	-10000	0	23
AKT1	0.014	0.058	0.14	63	-10000	0	63
IKBKG	0.016	0.037	0.14	27	-10000	0	27
CALM1	0.014	0.035	0.12	41	-10000	0	41
PIK3CA	-0.014	0.003	0	25	-10000	0	25
MAP3K1	0.021	0.053	0.15	50	-10000	0	50
MAP3K7	-0.014	0.001	0	1	-10000	0	1
mol:Ca2+	0.022	0.04	0.13	47	-10000	0	47
DOK1	-0.014	0	-10000	0	-10000	0	0
AP-1	0.028	0.051	0.14	58	-10000	0	58
LYN	-0.012	0.005	0	64	-10000	0	64
BLNK	-0.012	0.005	0	68	-10000	0	68
SHC1	-0.013	0.004	0	46	-10000	0	46
BCR complex	-0.017	0.001	0	2	-10000	0	2
CD22	-0.003	0.02	-10000	0	-10000	0	0
CAMK2G	0.007	0.031	0.12	26	-10000	0	26
CSNK2A1	-0.014	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.025	0.015	-10000	0	-10000	0	0
GO:0007205	0.022	0.04	0.13	45	-10000	0	45
SYK	-0.013	0.004	0	36	-10000	0	36
ELK1	0.016	0.039	0.12	43	-10000	0	43
NFATC1	0.017	0.055	0.14	63	-10000	0	63
B-cell antigen/BCR complex	-0.017	0.001	0	2	-10000	0	2
PAG1/CSK	-0.009	0	-10000	0	-10000	0	0
NFKBIB	0.011	0.018	0.079	18	-10000	0	18
HRAS	0.016	0.047	0.13	54	-10000	0	54
NFKBIA	0.011	0.018	0.079	17	-10000	0	17
NF-kappa-B/RelA/I kappa B beta	0.01	0.019	0.064	36	-10000	0	36
RasGAP/Csk	-0.02	0.012	0	133	-10000	0	133
mol:GDP	0.021	0.039	0.12	45	-10000	0	45
PTEN	-0.014	0.001	0	2	-10000	0	2
CD79B	-0.014	0.001	0	1	-10000	0	1
NF-kappa-B/RelA/I kappa B alpha	0.01	0.019	0.062	38	-10000	0	38
GRB2	-0.014	0.001	0	5	-10000	0	5
PI3K/BCAP/CD19	0.02	0.072	0.21	32	-0.17	10	42
PIK3R1	-0.013	0.004	0	36	-10000	0	36
mol:IP3	0.022	0.04	0.13	46	-10000	0	46
CSK	-0.014	0	-10000	0	-10000	0	0
FOS	0.034	0.059	0.12	135	-10000	0	135
CHUK	0.016	0.037	0.14	27	-10000	0	27
IBTK	-0.014	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	0.027	0.026	0.13	17	-10000	0	17
PTPN6	-0.001	0.029	0.081	34	-10000	0	34
RELA	-0.014	0	-10000	0	-10000	0	0
BCL2A1	0.01	0.024	0.064	75	-10000	0	75
VAV2	0.002	0.029	0.087	37	-10000	0	37
ubiquitin-dependent protein catabolic process	0.011	0.018	0.077	19	-10000	0	19
BTK	0.005	0.002	-10000	0	-10000	0	0
CD19	-0.003	0.02	-10000	0	-10000	0	0
MAP4K1	-0.014	0.001	0	1	-10000	0	1
CD72	-0.014	0	-10000	0	-10000	0	0
PAG1	0	0	-10000	0	-10000	0	0
MAPK14	0.015	0.05	0.14	52	-10000	0	52
SH3BP5	-0.013	0.004	0	49	-10000	0	49
PIK3AP1	0.022	0.038	0.13	43	-10000	0	43
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.002	0.02	0.12	7	-10000	0	7
RAF1	0.011	0.046	0.13	51	-10000	0	51
RasGAP/p62DOK/SHIP	-0.019	0.011	0	133	-10000	0	133
CD79A	-0.014	0.001	0	2	-10000	0	2
re-entry into mitotic cell cycle	0.028	0.051	0.14	58	-10000	0	58
RASA1	-0.014	0.002	0	8	-10000	0	8
MAPK3	0.002	0.042	0.12	43	-10000	0	43
MAPK1	0.002	0.042	0.12	42	-10000	0	42
CD72/SHP1	0.013	0.057	0.12	92	-10000	0	92
NFKB1	-0.014	0.001	0	4	-10000	0	4
MAPK8	0.015	0.05	0.14	50	-10000	0	50
actin cytoskeleton organization	0.019	0.061	0.16	64	-10000	0	64
NF-kappa-B/RelA	0.02	0.036	0.14	27	-10000	0	27
Calcineurin	0.003	0.033	0.099	33	-10000	0	33
PI3K	-0.019	0.02	-10000	0	-10000	0	0
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.013	0.026	0.1	23	-10000	0	23
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	0.033	0.04	-10000	0	-10000	0	0
DAPP1	0.021	0.034	-10000	0	-10000	0	0
cytokine secretion	0.017	0.054	0.14	63	-10000	0	63
mol:DAG	0.022	0.04	0.13	46	-10000	0	46
PLCG2	-0.014	0.002	0	10	-10000	0	10
MAP2K1	0.006	0.044	0.13	43	-10000	0	43
B-cell antigen/BCR complex/FcgammaRIIB	-0.015	0.009	0	128	-10000	0	128
mol:PI-3-4-5-P3	-0.003	0.042	0.1	49	-10000	0	49
ETS1	0.019	0.049	0.13	58	-10000	0	58
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.022	0.011	-10000	0	-10000	0	0
B-cell antigen/BCR complex/LYN	-0.006	0.005	-10000	0	-10000	0	0
MALT1	-0.014	0.003	0	24	-10000	0	24
TRAF6	-0.014	0	-10000	0	-10000	0	0
RAC1	0.018	0.059	0.16	63	-10000	0	63
B-cell antigen/BCR complex/LYN/SYK	-0.015	0.02	-10000	0	-10000	0	0
CARD11	0.021	0.038	0.12	46	-10000	0	46
FCGR2B	-0.011	0.006	0	128	-10000	0	128
PPP3CA	-0.011	0.006	0	101	-10000	0	101
BCL10	-0.014	0.001	0	4	-10000	0	4
IKK complex	0.01	0.024	0.086	30	-10000	0	30
PTPRC	-0.011	0.006	0	127	-10000	0	127
PDPK1	0.007	0.055	0.12	75	-10000	0	75
PPP3CB	-0.014	0.002	0	8	-10000	0	8
PPP3CC	-0.014	0	-10000	0	-10000	0	0
POU2F2	0.004	0.013	0.052	18	-10000	0	18

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.014	0.086	0.29	47	-10000	0	47
regulation of axonogenesis	0.002	0.027	-10000	0	-0.084	47	47
myoblast fusion	-0.011	0.05	-10000	0	-0.17	47	47
mol:GTP	0.015	0.027	0.1	45	-10000	0	45
regulation of calcium-dependent cell-cell adhesion	-0.003	0.043	-10000	0	-0.14	45	45
ARF1/GTP	0.018	0.024	0.094	45	-10000	0	45
mol:GM1	0.006	0.028	0.095	47	-10000	0	47
mol:Choline	-0.007	0.027	0.079	47	-10000	0	47
lamellipodium assembly	0.008	0.05	0.17	45	-10000	0	45
MAPK3	0.004	0.056	0.18	47	-10000	0	47
ARF6/GTP/NME1/Tiam1	0.003	0.043	0.14	45	-10000	0	45
ARF1	-0.014	0.001	0	2	-10000	0	2
ARF6/GDP	0.011	0.05	0.17	47	-10000	0	47
ARF1/GDP	0.005	0.046	0.15	47	-10000	0	47
ARF6	-0.006	0.024	0.069	47	-10000	0	47
RAB11A	-0.014	0.001	0	1	-10000	0	1
TIAM1	-0.011	0.011	0.023	45	-10000	0	45
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.005	0.056	0.18	47	-10000	0	47
actin filament bundle formation	0.006	0.014	-10000	0	-0.17	2	2
KALRN	-0.006	0.002	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	-0.017	0.001	0	1	-10000	0	1
RhoA/GDP	0.006	0.046	0.15	47	-10000	0	47
NME1	0	0.005	0.015	45	-10000	0	45
Rac1/GDP	0.006	0.046	0.15	47	-10000	0	47
substrate adhesion-dependent cell spreading	0.015	0.027	0.1	45	-10000	0	45
cortical actin cytoskeleton organization	-0.006	0.006	-10000	0	-10000	0	0
RAC1	-0.014	0	-10000	0	-10000	0	0
liver development	0.015	0.027	0.1	45	-10000	0	45
ARF6/GTP	0.015	0.027	0.1	45	-10000	0	45
RhoA/GTP	0.018	0.024	0.094	45	-10000	0	45
mol:GDP	-0.004	0.001	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0.022	0.024	0.093	47	-10000	0	47
RHOA	-0.014	0.001	0	2	-10000	0	2
PLD1	-0.001	0.03	0.095	47	-10000	0	47
RAB11FIP3	-0.014	0	-10000	0	-10000	0	0
tube morphogenesis	0.008	0.05	0.17	45	-10000	0	45
ruffle organization	-0.002	0.027	0.084	47	-10000	0	47
regulation of epithelial cell migration	0.015	0.027	0.1	45	-10000	0	45
PLD2	-0.001	0.03	0.095	47	-10000	0	47
PIP5K1A	-0.002	0.027	0.084	47	-10000	0	47
mol:Phosphatidic acid	-0.007	0.027	0.079	47	-10000	0	47
Rac1/GTP	-0.006	0.006	-10000	0	-10000	0	0

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.006	0.015	0.064	11	-10000	0	11
alphaM/beta2 Integrin/GPIbA	-0.011	0.017	0.063	15	-10000	0	15
alphaM/beta2 Integrin/proMMP-9	-0.008	0.015	0.064	9	-10000	0	9
PLAUR	-0.013	0.004	0	47	-10000	0	47
HMGB1	-0.011	0.018	0.043	53	-10000	0	53
alphaM/beta2 Integrin/Talin	-0.01	0.017	0.063	15	-10000	0	15
AGER	-0.011	0.017	0.042	50	-10000	0	50
RAP1A	-0.014	0	-10000	0	-10000	0	0
SELPLG	-0.014	0	-10000	0	-10000	0	0
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.017	0.015	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	-0.009	0.007	0	179	-10000	0	179
CYR61	-0.01	0.007	0	163	-10000	0	163
TLN1	-0.013	0.004	0	46	-10000	0	46
Rap1/GTP	0.003	0.018	-10000	0	-10000	0	0
RHOA	-0.014	0.001	0	2	-10000	0	2
P-selectin oligomer	-0.014	0.001	0	1	-10000	0	1
MYH2	0.017	0.043	0.13	41	-0.098	1	42
MST1R	-0.014	0.001	0	2	-10000	0	2
leukocyte activation during inflammatory response	-0.011	0.017	0.058	16	-10000	0	16
APOB	-0.014	0.001	0	3	-10000	0	3
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	-0.007	0.007	0	250	-10000	0	250
JAM3	-0.014	0.003	0	19	-10000	0	19
GP1BA	-0.014	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/CTGF	-0.01	0.017	0.063	14	-10000	0	14
alphaM/beta2 Integrin	0.009	0.023	0.065	16	-10000	0	16
JAM3 homodimer	-0.014	0.003	0	19	-10000	0	19
ICAM2	-0.014	0.001	0	3	-10000	0	3
ICAM1	-0.014	0.003	0	17	-10000	0	17
phagocytosis triggered by activation of immune response cell surface activating receptor	0.009	0.023	0.065	16	-10000	0	16
cell adhesion	-0.011	0.017	0.063	15	-10000	0	15
NFKB1	0.007	0.056	0.083	181	-10000	0	181
THY1	-0.01	0.006	0	142	-10000	0	142
RhoA/GDP	-0.009	0.001	0	2	-10000	0	2
Lipoprotein(a)	-0.013	0.001	0	3	-10000	0	3
alphaM/beta2 Integrin/LRP/tPA	-0.006	0.017	0.07	12	-10000	0	12
IL6	0.003	0.051	0.072	181	-10000	0	181
ITGB2	-0.008	0.012	0.04	16	-10000	0	16
elevation of cytosolic calcium ion concentration	-0.012	0.016	0.064	9	-10000	0	9
alphaM/beta2 Integrin/JAM2/JAM3	-0.01	0.017	0.066	11	-10000	0	11
JAM2	-0.012	0.005	0	81	-10000	0	81
alphaM/beta2 Integrin/ICAM1	-0.014	0.02	0.069	15	-10000	0	15
alphaM/beta2 Integrin/uPA/Plg	-0.012	0.016	0.066	9	-10000	0	9
RhoA/GTP	0	0.011	-10000	0	-10000	0	0
positive regulation of phagocytosis	-0.006	0.019	0.062	15	-10000	0	15
Ron/MSP	-0.017	0.002	0	8	-10000	0	8
alphaM/beta2 Integrin/uPAR/uPA	-0.012	0.016	0.066	9	-10000	0	9
alphaM/beta2 Integrin/uPAR	-0.011	0.016	0.063	13	-10000	0	13
PLAU	-0.011	0.006	0	123	-10000	0	123
PLAT	-0.008	0.007	0	244	-10000	0	244
actin filament polymerization	0.018	0.045	0.13	44	-10000	0	44
MST1	-0.014	0.002	0	6	-10000	0	6
alphaM/beta2 Integrin/lipoprotein(a)	-0.011	0.018	0.064	16	-10000	0	16
TNF	0.028	0.093	0.26	51	-10000	0	51
RAP1B	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.01	0.015	0.064	9	-10000	0	9
fibrinolysis	-0.012	0.016	0.064	9	-10000	0	9
HCK	-0.012	0.005	0	86	-10000	0	86
dendritic cell antigen processing and presentation	0.009	0.023	0.065	16	-10000	0	16
VTN	-0.014	0.001	0	2	-10000	0	2
alphaM/beta2 Integrin/CYR61	-0.009	0.014	0.063	7	-10000	0	7
LPA	-0.014	0	-10000	0	-10000	0	0
LRP1	-0.014	0.003	0	18	-10000	0	18
cell migration	-0.005	0.014	0.062	9	-10000	0	9
FN1	-0.011	0.006	0	104	-10000	0	104
alphaM/beta2 Integrin/Thy1	-0.008	0.013	0.063	6	-10000	0	6
MPO	-0.014	0	-10000	0	-10000	0	0
KNG1	-0.014	0.001	0	1	-10000	0	1
RAP1/GDP	-0.007	0	-10000	0	-10000	0	0
ROCK1	0.017	0.043	0.12	46	-0.098	1	47
ELA2	-0.014	0	-10000	0	-10000	0	0
PLG	-0.014	0	-10000	0	-10000	0	0
CTGF	-0.013	0.004	0	43	-10000	0	43
alphaM/beta2 Integrin/Hck	-0.011	0.017	0.063	14	-10000	0	14
ITGAM	-0.011	0.018	0.043	53	-10000	0	53
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.012	0.019	0.069	16	-10000	0	16
HP	-0.012	0.005	0	84	-10000	0	84
leukocyte adhesion	-0.007	0.026	0.068	33	-10000	0	33
SELP	-0.014	0.001	0	1	-10000	0	1

×

E-cadherin signaling in the nascent adherens junction

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.006	0.011	-10000	0	-10000	0	0
KLHL20	0.022	0.087	0.2	97	-10000	0	97
CYFIP2	-0.008	0.007	0	225	-10000	0	225
Rac1/GDP	-0.011	0.025	0.089	6	-10000	0	6
ENAH	-0.007	0.009	-10000	0	-10000	0	0
AP1M1	0	0	-10000	0	-10000	0	0
RAP1B	0	0	0	99	-10000	0	99
RAP1A	-0.014	0	-10000	0	-10000	0	0
CTNNB1	-0.014	0.001	-10000	0	-10000	0	0
CDC42/GTP	-0.022	0.018	0.032	9	-10000	0	9
ABI1/Sra1/Nap1	-0.008	0.01	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.015	0.019	0.025	95	-10000	0	95
RAPGEF1	-0.013	0.014	-10000	0	-10000	0	0
CTNND1	-0.014	0.002	0	10	-10000	0	10
regulation of calcium-dependent cell-cell adhesion	-0.002	0.008	-10000	0	-10000	0	0
CRK	-0.009	0.015	-10000	0	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	-0.013	0.015	0.019	90	-10000	0	90
alphaE/beta7 Integrin	-0.017	0.001	0	4	-10000	0	4
IQGAP1	-0.011	0.006	0	127	-10000	0	127
NCKAP1	-0.014	0	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	-0.007	0.01	0.015	99	-10000	0	99
DLG1	-0.006	0.011	-10000	0	-10000	0	0
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.02	0.017	0.015	70	-10000	0	70
MLLT4	-0.014	0	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.007	0.01	0.014	93	-10000	0	93
PI3K	-0.024	0.023	0.026	70	-10000	0	70
ARF6	-0.014	0.001	-10000	0	-10000	0	0
mol:Ca2+	0	0	0.001	99	-10000	0	99
E-cadherin/gamma catenin	-0.016	0.003	0	19	-10000	0	19
TIAM1	-0.013	0.003	0	21	-10000	0	21
E-cadherin(dimer)/Ca2+	-0.013	0.019	0.029	90	-10000	0	90
AKT1	-0.018	0.017	0.046	12	-10000	0	12
PIK3R1	-0.013	0.004	0	36	-10000	0	36
CDH1	-0.014	0.002	0	8	-10000	0	8
RhoA/GDP	-0.013	0.02	-10000	0	-10000	0	0
actin cytoskeleton organization	0.02	0.073	0.17	99	-10000	0	99
CDC42/GDP	-0.013	0.02	-10000	0	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.007	0.002	-10000	0	-10000	0	0
ITGB7	-0.014	0.001	0	2	-10000	0	2
RAC1	-0.014	0.001	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.014	0.021	0.031	90	-10000	0	90
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.01	0.014	0.021	95	-10000	0	95
mol:GDP	-0.012	0.018	-10000	0	-10000	0	0
CDC42/GTP/IQGAP1	-0.01	0.006	0	127	-10000	0	127
JUP	-0.014	0.002	0	16	-10000	0	16
p120 catenin/RhoA/GDP	-0.015	0.02	0.078	4	-10000	0	4
RAC1/GTP/IQGAP1	-0.006	0.01	0.005	207	-10000	0	207
PIP5K1C/AP1M1	-0.008	0.002	0	20	-10000	0	20
RHOA	-0.014	0.001	0	2	-10000	0	2
CDC42	-0.014	0	-10000	0	-10000	0	0
CTNNA1	-0.014	0	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.01	0.006	-10000	0	-10000	0	0
NME1	0	0	-10000	0	-10000	0	0
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.006	0.011	-10000	0	-10000	0	0
regulation of cell-cell adhesion	-0.021	0.014	0.017	5	-10000	0	5
WASF2	-0.005	0.006	-10000	0	-10000	0	0
Rap1/GTP	-0.02	0.018	0.056	5	-10000	0	5
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.017	0.02	0.027	90	-10000	0	90
CCND1	-0.012	0.007	-10000	0	-10000	0	0
VAV2	0.007	0.026	-10000	0	-10000	0	0
RAP1/GDP	-0.016	0.018	0.065	7	-10000	0	7
adherens junction assembly	-0.006	0.012	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	-0.014	0	-10000	0	-10000	0	0
PIP5K1C	-0.014	0.003	0	20	-10000	0	20
regulation of heterotypic cell-cell adhesion	-0.028	0.018	0.091	11	-10000	0	11
E-cadherin/beta catenin	-0.01	0.01	-10000	0	-0.029	121	121
mol:GTP	0	0	0.001	99	-10000	0	99
SRC	-0.004	0.015	-10000	0	-10000	0	0
PIK3CA	-0.014	0.003	0	25	-10000	0	25
Rac1/GTP	-0.019	0.01	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin	-0.012	0.017	0.024	95	-10000	0	95
ITGAE	-0.014	0.001	0	2	-10000	0	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.002	0.008	-10000	0	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	-0.014	0.001	0	3	-10000	0	3
LAT2	-0.007	0.012	0.052	8	-10000	0	8
AP1	0.01	0.035	-10000	0	-10000	0	0
mol:PIP3	0.016	0.056	0.17	40	-0.12	2	42
IKBKB	0.009	0.04	0.12	40	-0.08	2	42
AKT1	0.02	0.058	0.14	32	-10000	0	32
IKBKG	0.009	0.04	0.12	41	-0.08	2	43
MS4A2	-0.01	0.009	0.01	44	-10000	0	44
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	-0.013	0.003	0	26	-10000	0	26
MAP3K1	0.013	0.045	0.12	49	-0.11	1	50
mol:Ca2+	0.015	0.049	0.15	40	-0.098	2	42
LYN	-0.003	0.013	0.012	200	-10000	0	200
CBLB	-0.006	0.013	0.056	9	-10000	0	9
SHC1	-0.013	0.004	0	46	-10000	0	46
RasGAP/p62DOK	-0.017	0.004	0	26	-10000	0	26
positive regulation of cell migration	-0.009	0.001	0	4	-10000	0	4
INPP5D	0	0	-10000	0	-10000	0	0
PLD2	0.028	0.057	0.084	259	-10000	0	259
PTPN13	0.025	0.057	0.2	4	-0.58	2	6
PTPN11	-0.002	0.014	0.018	68	-10000	0	68
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	0.012	0.047	0.14	10	-0.28	2	12
SYK	-0.002	0.014	0.013	231	-10000	0	231
GRB2	-0.014	0.002	0.002	6	-10000	0	6
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.014	0.016	-10000	0	-0.11	2	2
LAT	-0.006	0.013	0.056	9	-10000	0	9
PAK2	0.018	0.047	0.12	56	-0.11	1	57
NFATC2	-0.004	0.004	0.001	1	-10000	0	1
HRAS	0.019	0.042	0.12	47	-0.12	2	49
GAB2	-0.014	0.001	0	4	-10000	0	4
PLA2G1B	-0.006	0.014	-10000	0	-10000	0	0
Fc epsilon R1	-0.011	0.012	0.021	2	-10000	0	2
Antigen/IgE/Fc epsilon R1	-0.009	0.012	-10000	0	-10000	0	0
mol:GDP	0.02	0.039	0.13	29	-0.15	2	31
JUN	-0.014	0.001	0	1	-10000	0	1
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	-0.013	0.004	0	37	-10000	0	37
FOS	-0.011	0.006	0	127	-10000	0	127
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.005	0.01	0.046	12	-10000	0	12
CHUK	0.009	0.04	0.12	41	-10000	0	41
KLRG1	-0.006	0.013	0.058	10	-10000	0	10
VAV1	-0.007	0.013	0.075	5	-10000	0	5
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.006	0.013	0.056	9	-10000	0	9
negative regulation of mast cell degranulation	-0.006	0.012	0.052	10	-10000	0	10
BTK	0.018	0.034	0.13	18	-0.15	2	20
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	0.008	0.026	0.048	147	-0.066	7	154
GAB2/PI3K/SHP2	-0.017	0.02	-10000	0	-10000	0	0
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.006	0.008	0.046	5	-10000	0	5
RAF1	0	0.011	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.011	0.012	-10000	0	-10000	0	0
FCER1G	-0.008	0.008	0.011	4	-10000	0	4
FCER1A	-0.001	0.014	0.013	253	-10000	0	253
Antigen/IgE/Fc epsilon R1/Fyn	-0.012	0.013	-10000	0	-10000	0	0
MAPK3	-0.005	0.012	-10000	0	-10000	0	0
MAPK1	-0.009	0.023	-10000	0	-10000	0	0
NFKB1	-0.014	0.001	0	4	-10000	0	4
MAPK8	0.005	0.079	-10000	0	-0.38	21	21
DUSP1	-0.014	0.003	0	18	-10000	0	18
NF-kappa-B/RelA	-0.001	0.022	0.055	18	-0.059	2	20
actin cytoskeleton reorganization	0.025	0.054	0.19	1	-0.59	2	3
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	0.013	0.041	0.11	40	-0.11	2	42
FER	-0.006	0.013	0.056	9	-10000	0	9
RELA	-0.014	0	-10000	0	-10000	0	0
ITK	-0.001	0.006	0.067	3	-10000	0	3
SOS1	0	0	-10000	0	-10000	0	0
PLCG1	0.017	0.043	0.12	37	-0.15	2	39
cytokine secretion	-0.003	0.014	0.026	5	-0.044	2	7
SPHK1	-0.007	0.011	0.069	3	-10000	0	3
PTK2	0.025	0.055	-10000	0	-0.62	2	2
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.012	0.015	-10000	0	-0.11	2	2
EDG1	-0.009	0.001	0	4	-10000	0	4
mol:DAG	0.017	0.055	0.16	41	-0.12	2	43
MAP2K2	-0.006	0.01	-10000	0	-10000	0	0
MAP2K1	-0.006	0.01	-10000	0	-10000	0	0
MAP2K7	-0.014	0	-10000	0	-10000	0	0
KLRG1/SHP2	-0.007	0.014	0.08	5	-10000	0	5
MAP2K4	-0.02	0.16	-10000	0	-0.8	21	21
Fc epsilon R1/FcgammaRIIB	-0.012	0.013	-10000	0	-10000	0	0
mol:Choline	0.028	0.056	0.083	259	-10000	0	259
SHC/Grb2/SOS1	0.011	0.033	0.08	31	-10000	0	31
FYN	-0.014	0.003	0	21	-10000	0	21
DOK1	-0.014	0	-10000	0	-10000	0	0
PXN	0.019	0.052	-10000	0	-0.58	2	2
HCLS1	-0.007	0.012	0.052	8	-10000	0	8
PRKCB	0.014	0.048	0.14	41	-0.098	2	43
FCGR2B	-0.011	0.006	0	128	-10000	0	128
IGHE	0.001	0.003	0.006	61	-10000	0	61
KLRG1/SHIP	-0.006	0.012	0.053	10	-10000	0	10
LCP2	-0.013	0.003	0	30	-10000	0	30
PLA2G4A	-0.005	0.009	-10000	0	-10000	0	0
RASA1	-0.014	0.002	0	8	-10000	0	8
mol:Phosphatidic acid	0.028	0.056	0.083	259	-10000	0	259
IKK complex	0.003	0.035	0.11	35	-10000	0	35
WIPF1	-0.014	0.002	0	11	-10000	0	11

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.008	0.064	0.17	31	-0.13	2	33
TBX21	-0.023	0.18	0.49	16	-0.52	2	18
B2M	-0.014	0	-10000	0	-10000	0	0
TYK2	-0.007	0.03	0.073	31	-10000	0	31
IL12RB1	-0.007	0.03	0.073	31	-10000	0	31
GADD45B	-0.012	0.16	0.48	16	-10000	0	16
IL12RB2	-0.007	0.03	0.076	31	-10000	0	31
GADD45G	-0.01	0.16	0.48	12	-10000	0	12
natural killer cell activation	0.001	0.022	0.067	31	-10000	0	31
RELB	-0.014	0.001	0	1	-10000	0	1
RELA	-0.014	0	-10000	0	-10000	0	0
IL18	-0.011	0.013	0.034	26	-10000	0	26
IL2RA	-0.014	0.002	0	6	-10000	0	6
IFNG	-0.014	0.001	0	1	-10000	0	1
STAT3 (dimer)	-0.02	0.16	0.41	20	-0.44	2	22
HLA-DRB5	0.005	0.009	0.021	125	-0.014	2	127
FASLG	-0.023	0.18	0.48	17	-0.52	2	19
NF kappa B2 p52/RelB	-0.047	0.15	-10000	0	-0.52	2	2
CD4	-0.005	0.018	0.029	113	-10000	0	113
SOCS1	-0.014	0	-10000	0	-10000	0	0
EntrezGene:6955	0.005	0.01	0.023	125	-0.019	2	127
CD3D	-0.004	0.019	0.032	119	-0.034	2	121
CD3E	-0.004	0.019	0.03	125	-10000	0	125
CD3G	-0.004	0.02	0.032	125	-0.034	2	127
IL12Rbeta2/JAK2	-0.005	0.046	0.12	31	-10000	0	31
CCL3	-0.021	0.18	0.44	23	-0.52	2	25
CCL4	-0.09	0.32	0.49	19	-0.77	85	104
HLA-A	-0.014	0.001	0	1	-10000	0	1
IL18/IL18R	-0.001	0.051	0.18	32	-10000	0	32
NOS2	-0.016	0.17	0.43	24	-0.45	2	26
IL12/IL12R/TYK2/JAK2/SPHK2	-0.008	0.064	0.17	31	-10000	0	31
IL1R1	-0.022	0.18	0.5	17	-0.52	2	19
IL4	-0.012	0.028	-10000	0	-0.092	23	23
JAK2	-0.007	0.03	0.073	31	-10000	0	31
EntrezGene:6957	0.005	0.009	0.021	125	-0.014	2	127
TCR/CD3/MHC I/CD8	0.007	0.024	0.06	24	-0.048	2	26
RAB7A	-0.009	0.15	0.46	11	-10000	0	11
lysosomal transport	-0.008	0.14	0.46	11	-10000	0	11
FOS	0.062	0.19	0.37	93	-0.99	2	95
STAT4 (dimer)	-0.041	0.17	0.42	18	-0.46	1	19
STAT5A (dimer)	-0.047	0.15	-10000	0	-0.52	2	2
GZMA	-0.02	0.19	0.56	17	-0.52	2	19
GZMB	-0.022	0.18	0.54	17	-0.52	2	19
HLX	-0.014	0.001	0	5	-10000	0	5
LCK	-0.027	0.19	0.45	23	-0.54	2	25
TCR/CD3/MHC II/CD4	0.04	0.081	0.18	124	-10000	0	124
IL2/IL2R	-0.023	0.004	0	15	-10000	0	15
MAPK14	-0.01	0.16	0.44	17	-10000	0	17
CCR5	-0.011	0.16	0.53	14	-10000	0	14
IL1B	-0.007	0.029	0.074	29	-10000	0	29
STAT6	0.002	0.084	0.27	20	-10000	0	20
STAT4	-0.008	0.007	0	219	-10000	0	219
STAT3	-0.014	0.002	0	10	-10000	0	10
STAT1	-0.014	0.003	0	18	-10000	0	18
NFKB1	-0.014	0.001	0	4	-10000	0	4
NFKB2	-0.014	0	-10000	0	-10000	0	0
IL12B	-0.007	0.03	0.076	31	-10000	0	31
CD8A	0	0	-10000	0	-10000	0	0
CD8B	-0.014	0.001	0	2	-10000	0	2
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.008	0.063	0.13	2	-0.17	31	33
IL2RB	-0.014	0.001	0	4	-10000	0	4
proteasomal ubiquitin-dependent protein catabolic process	-0.038	0.16	0.41	19	-0.44	1	20
IL2RG	-0.014	0.002	0	9	-10000	0	9
IL12	-0.005	0.046	0.12	31	-10000	0	31
STAT5A	-0.014	0.001	0	1	-10000	0	1
CD247	-0.004	0.019	0.03	124	-10000	0	124
IL2	-0.014	0	-10000	0	-10000	0	0
SPHK2	-0.014	0	-10000	0	-10000	0	0
FRAP1	-0.014	0.001	0	1	-10000	0	1
IL12A	-0.007	0.03	0.073	31	-10000	0	31
IL12/IL12R/TYK2/JAK2	-0.022	0.2	0.49	23	-0.56	2	25
MAP2K3	-0.01	0.16	0.5	11	-10000	0	11
RIPK2	-0.014	0.001	0	1	-10000	0	1
MAP2K6	-0.01	0.16	0.44	18	-10000	0	18
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.003	0.011	0.03	35	-10000	0	35
IL18RAP	-0.011	0.014	0.036	32	-10000	0	32
IL12Rbeta1/TYK2	-0.007	0.04	0.1	31	-10000	0	31
EOMES	0	0.032	0.089	1	-0.11	22	23
STAT1 (dimer)	-0.021	0.16	0.4	18	-0.43	2	20
T cell proliferation	-0.038	0.14	0.36	22	-10000	0	22
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.011	0.014	0.036	32	-10000	0	32
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.071	0.1	-10000	0	-10000	0	0
ATF2	-0.014	0.15	0.47	11	-10000	0	11

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.014	0	-10000	0	-10000	0	0
SPHK1	-0.014	0.003	0	19	-10000	0	19
GNAI2	-0.014	0.001	0	1	-10000	0	1
mol:S1P	-0.005	0.001	-10000	0	-10000	0	0
GNAO1	-0.001	0.004	0	481	-10000	0	481
mol:Sphinganine-1-P	-0.016	0.003	0	19	-10000	0	19
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	-0.011	0.015	0.057	25	-10000	0	25
GNAI3	-0.012	0.005	0	65	-10000	0	65
G12/G13	-0.017	0.002	0	6	-10000	0	6
S1PR3	0	0	-10000	0	-10000	0	0
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	-0.014	0.001	0	4	-10000	0	4
S1P1/S1P	-0.007	0.015	0.061	25	-10000	0	25
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
GNAI1	-0.012	0.005	0	81	-10000	0	81
S1P/S1P5/G12	-0.007	0.013	0.051	24	-10000	0	24
S1P/S1P3/Gq	-0.002	0.008	-10000	0	-10000	0	0
S1P/S1P4/Gi	-0.008	0.043	0.049	3	-0.26	15	18
GNAQ	-0.014	0	-10000	0	-10000	0	0
GNAZ	-0.012	0.005	0	72	-10000	0	72
GNA14	-0.014	0.001	0	2	-10000	0	2
GNA15	-0.014	0.002	0	7	-10000	0	7
GNA12	-0.014	0.001	0	4	-10000	0	4
GNA13	-0.014	0.001	0	2	-10000	0	2
GNA11	-0.014	0	-10000	0	-10000	0	0
ABCC1	-0.014	0.002	0	9	-10000	0	9

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	-0.009	0	0	1	-9999	1
PRKCZ	0	0	-10000	0	-9999	0
MAP3K7IP2	-0.014	0	-10000	0	-9999	0
ERC1	-0.014	0.001	0	1	-9999	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.003	0.012	0.049	22	-9999	22
IRAK/TOLLIP	-0.018	0.001	-10000	0	-9999	0
IKBKB	-0.014	0	-10000	0	-9999	0
IKBKG	-0.014	0	-10000	0	-9999	0
IL1 alpha/IL1R2	-0.016	0.005	0	43	-9999	43
IL1A	-0.014	0.001	0	3	-9999	3
IL1B	-0.011	0.008	0	179	-9999	179
IRAK/TRAF6/p62/Atypical PKCs	-0.025	0.002	-10000	0	-9999	0
IL1R2	-0.013	0.004	0	40	-9999	40
IL1R1	-0.014	0.001	0	3	-9999	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.007	0.024	-10000	0	-9999	0
TOLLIP	-0.014	0	-10000	0	-9999	0
TICAM2	0	0	-10000	0	-9999	0
MAP3K3	-0.014	0	-10000	0	-9999	0
TAK1/TAB1/TAB2	-0.02	0.001	0	1	-9999	1
IKK complex/ELKS	-0.021	0.004	-10000	0	-9999	0
JUN	-0.036	0.005	0.06	1	-9999	1
MAP3K7	-0.014	0.001	0	1	-9999	1
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.003	0.048	0.085	127	-9999	127
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.019	0.01	0	111	-9999	111
PIK3R1	-0.013	0.004	0	36	-9999	36
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.021	0.011	-10000	0	-9999	0
IL1 beta fragment/IL1R1/IL1RAP	-0.015	0.011	0	199	-9999	199
NFKB1	-0.014	0.001	0	4	-9999	4
MAPK8	-0.033	0.005	0.069	1	-9999	1
IRAK1	-0.013	0.001	0	2	-9999	2
IL1RN/IL1R1	-0.017	0.001	0	3	-9999	3
IRAK4	-0.014	0.001	0	1	-9999	1
PRKCI	-0.014	0.001	0	1	-9999	1
TRAF6	-0.014	0	-10000	0	-9999	0
PI3K	-0.015	0.005	0	60	-9999	60
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.009	0.029	0.06	108	-9999	108
CHUK	-0.014	0.001	0	1	-9999	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.015	0.011	0	199	-9999	199
IL1 beta/IL1R2	-0.011	0.016	0.11	5	-9999	5
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.03	0.002	-10000	0	-9999	0
NF kappa B1 p50/RelA	-0.022	0.019	-10000	0	-9999	0
IRAK3	-0.014	0.001	0	2	-9999	2
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.006	0.046	0.08	146	-9999	146
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.009	0.005	-10000	0	-9999	0
IL1 alpha/IL1R1/IL1RAP	-0.018	0.006	0	50	-9999	50
RELA	-0.014	0	-10000	0	-9999	0
MAP3K7IP1	-0.014	0	-10000	0	-9999	0
SQSTM1	-0.014	0.001	0	1	-9999	1
MYD88	-0.012	0.005	0	71	-9999	71
IRAK/TRAF6/MEKK3	-0.022	0.001	-10000	0	-9999	0
IL1RAP	-0.013	0.004	0	45	-9999	45
UBE2N	-0.014	0.001	0	1	-9999	1
IRAK/TRAF6	-0.023	0.018	-10000	0	-9999	0
CASP1	-0.01	0.007	0	173	-9999	173
IL1RN/IL1R2	-0.016	0.005	0	40	-9999	40
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.002	0.044	0.087	109	-9999	109
TMEM189-UBE2V1	0	0	-10000	0	-9999	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.003	0.014	-10000	0	-9999	0
PIK3CA	-0.014	0.003	0	25	-9999	25
IL1RN	-0.014	0	-10000	0	-9999	0
TRAF6/TAK1/TAB1/TAB2	-0.026	0.002	-10000	0	-9999	0
MAP2K6	-0.029	0.005	0.078	1	-9999	1

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.034	0.028	-10000	0	-0.11	11	11
CaM/Ca2+	-0.008	0.002	0	27	-10000	0	27
AKT1	-0.014	0.001	0	4	-10000	0	4
AKT2	-0.014	0	-10000	0	-10000	0	0
STXBP4	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.034	0.034	-10000	0	-0.1	37	37
YWHAZ	-0.014	0.002	0	6	-10000	0	6
CALM1	-0.013	0.003	0	27	-10000	0	27
YWHAQ	-0.014	0	-10000	0	-10000	0	0
TBC1D4	-0.017	0.001	0	4	-10000	0	4
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	-0.007	0.007	0	284	-10000	0	284
YWHAB	-0.014	0.001	0	2	-10000	0	2
SNARE/Synip	-0.012	0.004	0	49	-10000	0	49
YWHAG	0	0	-10000	0	-10000	0	0
ASIP	-0.014	0	-10000	0	-10000	0	0
PRKCI	-0.014	0.001	0	1	-10000	0	1
AS160/CaM/Ca2+	-0.008	0.002	0	27	-10000	0	27
RHOQ	-0.014	0	-10000	0	-10000	0	0
GYS1	-0.003	0.034	0.12	36	-10000	0	36
PRKCZ	0	0	-10000	0	-10000	0	0
TRIP10	-0.014	0.002	0	6	-10000	0	6
TC10/GTP/CIP4/Exocyst	-0.013	0.001	0	6	-10000	0	6
AS160/14-3-3	-0.048	0.042	0.049	2	-0.089	257	259
VAMP2	-0.013	0.004	0	49	-10000	0	49
SLC2A4	-0.037	0.036	-10000	0	-0.11	37	37
STX4	-0.014	0	-10000	0	-10000	0	0
GSK3B	-0.008	0.001	0	8	-10000	0	8
SFN	-0.013	0.003	0	33	-10000	0	33
LNPEP	-0.014	0.001	0	1	-10000	0	1
YWHAE	-0.014	0.001	0	2	-10000	0	2

×

FAS signaling pathway (CD95)

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
SPTAN1	-0.005	0.007	0.077	3	-10000	0	3
RFC1	-0.006	0.007	0.077	3	-10000	0	3
PRKDC	-0.002	0.021	0.11	17	-10000	0	17
RIPK1	-0.016	0.006	0	9	-0.032	51	60
CASP7	0.008	0.02	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.002	0.029	0.074	49	-0.067	25	74
MAP2K4	0.014	0.058	0.18	50	-0.13	1	51
mol:ceramide	0.008	0.051	0.15	50	-10000	0	50
GSN	-0.003	0.02	0.12	14	-10000	0	14
FASLG/FAS/FADD/FAF1/Caspase 8	0.002	0.041	0.1	51	-0.072	24	75
FAS	-0.01	0.01	0.026	33	-10000	0	33
BID	-0.015	0.012	0.026	18	-10000	0	18
MAP3K1	0.017	0.046	0.15	36	-10000	0	36
MAP3K7	-0.011	0.009	0.016	53	-10000	0	53
RB1	-0.006	0.007	0.077	3	-10000	0	3
CFLAR	-0.016	0.005	0	5	-0.032	50	55
HGF/MET	-0.019	0.005	0	41	-10000	0	41
ARHGDIB	0.003	0.032	0.12	35	-10000	0	35
FADD	-0.01	0.012	0.026	52	-10000	0	52
actin filament polymerization	0.002	0.023	-10000	0	-0.11	20	20
NFKB1	0.023	0.045	0.18	16	-10000	0	16
MAPK8	0.013	0.071	0.22	50	-10000	0	50
DFFA	-0.006	0.007	0.077	3	-10000	0	3
DNA fragmentation during apoptosis	-0.005	0.011	0.072	9	-10000	0	9
FAS/FADD/MET	-0.014	0.016	0.043	31	-10000	0	31
CFLAR/RIP1	-0.019	0.009	-10000	0	-0.044	49	49
FAIM3	-0.015	0.001	0	1	-10000	0	1
FAF1	-0.01	0.015	0.035	50	-10000	0	50
PARP1	-0.006	0.007	0.077	3	-10000	0	3
DFFB	-0.006	0.007	0.077	3	-10000	0	3
CHUK	0.013	0.04	-10000	0	-10000	0	0
FASLG	-0.01	0.015	0.035	52	-10000	0	52
FAS/FADD	-0.011	0.015	0.041	33	-10000	0	33
HGF	-0.014	0.001	0	2	-10000	0	2
LMNA	-0.004	0.026	0.1	27	-10000	0	27
CASP6	-0.002	0.023	0.11	19	-10000	0	19
CASP10	-0.01	0.012	0.026	52	-10000	0	52
CASP3	-0.001	0.003	-10000	0	-10000	0	0
PTPN13	-0.013	0.003	0	30	-10000	0	30
CASP8	-0.011	0.006	0.006	58	-10000	0	58
IL6	0.032	0.095	0.32	52	-10000	0	52
MET	-0.014	0.002	0	10	-10000	0	10
ICAD/CAD	-0.01	0.005	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	0.004	0.049	0.15	50	-10000	0	50
activation of caspase activity by cytochrome c	-0.015	0.012	0.026	18	-10000	0	18
PAK2	-0.002	0.021	0.11	16	-10000	0	16
BCL2	-0.014	0.001	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	-0.02	0.001	0	2	-9999	2
VEGFR1 homodimer/NRP1	-0.014	0.001	0	2	-9999	2
mol:DAG	-0.022	0.009	0.095	2	-9999	2
VEGFR1 homodimer/NRP1/VEGFR 121	-0.008	0.009	-10000	0	-9999	0
CaM/Ca2+	-0.025	0.011	0.09	2	-9999	2
HIF1A	-0.02	0.001	0	2	-9999	2
GAB1	-0.014	0.001	0	4	-9999	4
AKT1	-0.02	0.028	0.12	4	-9999	4
PLCG1	-0.022	0.009	0.095	2	-9999	2
NOS3	-0.019	0.026	0.11	2	-9999	2
CBL	-0.014	0	-10000	0	-9999	0
mol:NO	-0.018	0.026	0.11	2	-9999	2
FLT1	-0.017	0.001	0	2	-9999	2
PGF	-0.014	0.003	0	21	-9999	21
VEGFR1 homodimer/NRP2/VEGFR121	-0.011	0.012	-10000	0	-9999	0
CALM1	-0.013	0.003	0	27	-9999	27
PIK3CA	-0.014	0.003	0	25	-9999	25
eNOS/Hsp90	-0.022	0.028	0.11	2	-9999	2
endothelial cell proliferation	-0.015	0.02	0.089	2	-9999	2
mol:Ca2+	-0.022	0.009	0.095	2	-9999	2
MAPK3	-0.026	0.021	0.073	23	-9999	23
MAPK1	-0.025	0.022	0.073	23	-9999	23
PIK3R1	-0.013	0.004	0	36	-9999	36
PLGF homodimer	-0.014	0.003	0	21	-9999	21
PRKACA	-0.014	0	-10000	0	-9999	0
RP11-342D11.1	0	0	-10000	0	-9999	0
CAV1	-0.005	0.007	0	324	-9999	324
VEGFA homodimer	-0.006	0.007	0	287	-9999	287
VEGFR1 homodimer/VEGFA homodimer	-0.009	0.01	0	289	-9999	289
platelet activating factor biosynthetic process	-0.029	0.021	-10000	0	-9999	0
PI3K	-0.023	0.012	0.088	2	-9999	2
PRKCA	-0.023	0.022	0.08	23	-9999	23
PRKCB	-0.02	0.008	0.089	2	-9999	2
VEGFR1 homodimer/PLGF homodimer	-0.02	0.004	0	23	-9999	23
VEGFA	-0.006	0.007	0	287	-9999	287
VEGFB	-0.014	0	-10000	0	-9999	0
mol:IP3	-0.022	0.009	0.095	2	-9999	2
RASA1	-0.023	0.008	0.095	2	-9999	2
NRP2	-0.014	0.001	0	1	-9999	1
VEGFR1 homodimer	-0.017	0.001	0	2	-9999	2
VEGFB homodimer	-0.014	0	-10000	0	-9999	0
NCK1	-0.014	0.002	0	11	-9999	11
eNOS/Caveolin-1	-0.009	0.021	-10000	0	-9999	0
PTPN11	-0.014	0	-10000	0	-9999	0
mol:PI-3-4-5-P3	-0.023	0.012	0.085	2	-9999	2
mol:L-citrulline	-0.018	0.026	0.11	2	-9999	2
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.011	0.014	-10000	0	-9999	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.01	0.012	-10000	0	-9999	0
CD2AP	-0.013	0.004	0	49	-9999	49
PI3K/GAB1	-0.026	0.013	0.086	2	-9999	2
PDPK1	-0.02	0.031	0.13	4	-9999	4
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.011	0.012	-10000	0	-9999	0
mol:NADP	-0.018	0.026	0.11	2	-9999	2
HSP90AA1	-0.014	0	-10000	0	-9999	0
ubiquitin-dependent protein catabolic process	-0.011	0.013	-10000	0	-9999	0
VEGFR1 homodimer/NRP2	-0.02	0.002	0	3	-9999	3

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.013	0.008	0.056	1	-0.074	4	5
BIRC5	-0.009	0.007	0	211	-10000	0	211
NFKBIA	-0.014	0.007	0.12	1	-10000	0	1
CPEB1	-0.011	0.006	0	136	-10000	0	136
AKT1	-0.013	0.013	0.12	4	-10000	0	4
NDEL1	-0.014	0.003	0	25	-10000	0	25
Aurora A/BRCA1	-0.013	0.005	-10000	0	-0.065	4	4
NDEL1/TACC3	-0.014	0.009	0.047	1	-0.066	3	4
GADD45A	-0.013	0.004	0	46	-10000	0	46
GSK3B	-0.015	0.002	-10000	0	-10000	0	0
PAK1/Aurora A	-0.015	0.007	0.056	1	-0.074	4	5
MDM2	-0.014	0.003	0	18	-10000	0	18
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.007	0.008	0	298	-10000	0	298
TP53	-0.003	0.002	-10000	0	-10000	0	0
DLG7	0.027	0.062	0.12	150	-10000	0	150
AURKAIP1	-0.014	0	-10000	0	-10000	0	0
ARHGEF7	-0.014	0.001	0	1	-10000	0	1
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	-0.015	0.009	0.049	1	-0.071	3	4
G2/M transition of mitotic cell cycle	-0.013	0.005	-10000	0	-0.065	4	4
AURKA	-0.01	0.003	-10000	0	-10000	0	0
AURKB	0.001	0.001	-10000	0	-10000	0	0
CDC25B	-0.005	0.002	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.007	0.005	-10000	0	-0.059	4	4
mRNA polyadenylation	-0.009	0.006	-10000	0	-0.065	1	1
Aurora A/CPEB	-0.01	0.006	-10000	0	-0.065	1	1
Aurora A/TACC1/TRAP/chTOG	-0.021	0.015	0.054	18	-0.071	4	22
BRCA1	-0.014	0.001	0	5	-10000	0	5
centrosome duplication	-0.015	0.007	0.056	1	-0.074	4	5
regulation of centrosome cycle	-0.014	0.009	0.045	1	-0.066	3	4
spindle assembly	-0.02	0.014	0.052	18	-0.071	4	22
TDRD7	-0.014	0.001	0	1	-10000	0	1
Aurora A/RasGAP/Survivin	-0.013	0.012	0.048	1	-0.068	3	4
CENPA	0.001	0.001	-10000	0	-10000	0	0
Aurora A/PP2A	-0.015	0.007	0.056	1	-0.074	4	5
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.016	0.04	0.075	161	-10000	0	161
negative regulation of DNA binding	-0.003	0.002	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	-0.017	0.001	0	1	-10000	0	1
RASA1	-0.014	0.002	0	8	-10000	0	8
Ajuba/Aurora A	-0.007	0.005	-10000	0	-0.06	4	4
mitotic prometaphase	-0.002	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.01	0.003	-10000	0	-10000	0	0
TACC1	-0.014	0.001	0	3	-10000	0	3
TACC3	-0.012	0.005	0	96	-10000	0	96
Aurora A/Antizyme1	-0.017	0.014	0.051	19	-0.071	4	23
Aurora A/RasGAP	-0.014	0.007	0.056	1	-0.074	4	5
OAZ1	-0.014	0	-10000	0	-10000	0	0
RAN	-0.014	0.001	0	3	-10000	0	3
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	-0.015	0.001	-10000	0	-10000	0	0
GIT1	-0.014	0	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	-0.02	0.001	0	1	-10000	0	1
Importin alpha/Importin beta/TPX2	-0.007	0.008	0	298	-10000	0	298
PPP2R5D	-0.014	0	-10000	0	-10000	0	0
Aurora A/TPX2	-0.008	0.01	0.046	1	-0.071	2	3
PAK1	-0.014	0	-10000	0	-10000	0	0
CKAP5	-0.014	0	-10000	0	-10000	0	0

×

Visual signal transduction: Cones

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.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.011	0	-10000	0	-9999	0
RGS9BP	0	0	-10000	0	-9999	0
mol:GTP	0	0	-10000	0	-9999	0
GRK1	0	0	-10000	0	-9999	0
mol:Na +	-0.009	0.006	0	184	-9999	184
mol:ADP	0	0	-10000	0	-9999	0
GNAT2	-0.014	0	-10000	0	-9999	0
RGS9-1/Gbeta5/R9AP	-0.013	0.002	0	7	-9999	7
mol:GDP	0	0	-10000	0	-9999	0
PDE6H/GNAT2/GTP	-0.014	0	-10000	0	-9999	0
GRK7	0	0	-10000	0	-9999	0
CNGB3	-0.014	0	-10000	0	-9999	0
Cone Metarhodopsin II/X-Arrestin	-0.009	0	-10000	0	-9999	0
mol:Ca2+	0.022	0.055	0.097	184	-9999	184
Cone PDE6	-0.022	0.002	0	7	-9999	7
Cone Metarhodopsin II	0	0	-10000	0	-9999	0
Na + (4 Units)	-0.012	0.008	0	184	-9999	184
GNAT2/GDP	-0.016	0.002	0	7	-9999	7
GNB5	-0.014	0.002	0	7	-9999	7
mol:GMP (4 units)	-0.018	0	-10000	0	-9999	0
Cone Transducin	-0.012	0	-10000	0	-9999	0
SLC24A2	-0.014	0	-10000	0	-9999	0
GNB3/GNGT2	-0.009	0	-10000	0	-9999	0
GNB3	-0.014	0	-10000	0	-9999	0
GNAT2/GTP	-0.009	0	-10000	0	-9999	0
CNGA3	-0.009	0.007	0	184	-9999	184
ARR3	-0.014	0	-10000	0	-9999	0
absorption of light	0	0	-10000	0	-9999	0
cGMP/Cone CNG Channel	-0.009	0.006	0	184	-9999	184
mol:Pi	-0.013	0.002	0	7	-9999	7
Cone CNG Channel	-0.017	0.012	-10000	0	-9999	0
mol:all-trans-retinal	0	0	-10000	0	-9999	0
mol:K +	-0.014	0	-10000	0	-9999	0
RGS9	-0.014	0	-10000	0	-9999	0
PDE6C	-0.014	0	-10000	0	-9999	0
GNGT2	0	0	-10000	0	-9999	0
mol:cGMP (4 units)	0	0	-10000	0	-9999	0
PDE6H	-0.014	0	-10000	0	-9999	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.016	0.003	0	19	-10000	0	19
MAP4K4	0.005	0.025	0.04	178	-10000	0	178
BAG4	-0.014	0	-10000	0	-10000	0	0
PKC zeta/ceramide	0.004	0.014	-10000	0	-0.084	11	11
NFKBIA	-0.014	0.001	0	1	-10000	0	1
BIRC3	-0.013	0.003	0	33	-10000	0	33
BAX	0.005	0.008	-10000	0	-10000	0	0
RIPK1	-0.014	0.002	0	9	-10000	0	9
AKT1	-0.011	0.026	0.28	4	-10000	0	4
BAD	-0.001	0.014	-10000	0	-0.089	11	11
SMPD1	0.013	0.028	0.051	185	-10000	0	185
RB1	-0.001	0.014	-10000	0	-0.089	11	11
FADD/Caspase 8	0.005	0.028	0.084	18	-10000	0	18
MAP2K4	-0.006	0.014	0.1	1	-0.09	11	12
NSMAF	-0.014	0.001	0	2	-10000	0	2
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.006	0.014	0.1	1	-0.09	11	12
EGF	-0.014	0.001	0	2	-10000	0	2
mol:ceramide	0.004	0.015	-10000	0	-0.09	11	11
MADD	-0.014	0.001	0	4	-10000	0	4
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.016	0.003	0	20	-10000	0	20
ASAH1	-0.014	0.001	0	1	-10000	0	1
negative regulation of cell cycle	-0.001	0.014	-10000	0	-0.089	11	11
cell proliferation	-0.017	0.015	0.084	1	-0.091	11	12
BID	0.017	0.022	-10000	0	-10000	0	0
MAP3K1	-0.001	0.015	0.11	1	-0.089	11	12
EIF2A	-0.006	0.013	-10000	0	-0.086	11	11
TRADD	-0.014	0	-10000	0	-10000	0	0
CRADD	-0.014	0	-10000	0	-10000	0	0
MAPK3	-0.01	0.014	0.09	1	-0.089	11	12
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.013	0.024	0.09	1	-0.12	19	20
Cathepsin D/ceramide	0.008	0.016	-10000	0	-0.089	11	11
FADD	0.005	0.026	0.04	180	-10000	0	180
KSR1	-0.001	0.014	-10000	0	-0.089	11	11
MAPK8	-0.001	0.015	-10000	0	-0.085	11	11
PRKRA	-0.001	0.014	-10000	0	-0.089	11	11
PDGFA	-0.014	0.003	0	19	-10000	0	19
TRAF2	-0.014	0	-10000	0	-10000	0	0
IGF1	-0.014	0.001	0	4	-10000	0	4
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	0.004	0.015	-10000	0	-0.09	11	11
CTSD	-0.014	0.002	0	16	-10000	0	16
regulation of nitric oxide biosynthetic process	-0.017	0.001	0	4	-10000	0	4
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.018	0.016	0.091	1	-0.096	11	12
PRKCD	-0.014	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.016	0.003	0	20	-10000	0	20
RelA/NF kappa B1	-0.017	0.001	0	4	-10000	0	4
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.014	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.01	0.027	0.048	179	-10000	0	179
TNFR1A/BAG4/TNF-alpha	-0.013	0.01	0	185	-10000	0	185
mol:Sphingosine-1-phosphate	-0.016	0.003	0	19	-10000	0	19
MAP2K1	-0.011	0.014	0.091	1	-0.091	11	12
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	-0.014	0	-10000	0	-10000	0	0
CYCS	0.001	0.01	-10000	0	-10000	0	0
TNFRSF1A	-0.009	0.007	0	183	-10000	0	183
NFKB1	-0.014	0.001	0	4	-10000	0	4
TNFR1A/BAG4	-0.011	0.008	0	183	-10000	0	183
EIF2AK2	-0.006	0.014	-10000	0	-0.09	11	11
TNF-alpha/TNFR1A/FAN	-0.013	0.01	0	187	-10000	0	187
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.01	0.016	-10000	0	-10000	0	0
MAP2K2	-0.011	0.014	0.091	1	-0.091	11	12
SMPD3	0.016	0.029	0.075	24	-10000	0	24
TNF	-0.014	0.001	0	2	-10000	0	2
PKC zeta/PAR4	-0.009	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.01	0.013	-10000	0	-0.066	9	9
NF kappa B1/RelA/I kappa B alpha	-0.022	0.002	0	5	-10000	0	5
AIFM1	0.002	0.013	0.087	1	-10000	0	1
BCL2	-0.014	0	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.001	0.003	-10000	0	-10000	0	0
epithelial cell differentiation	-0.021	0.004	0	18	-10000	0	18
CYFIP2	-0.008	0.007	0	225	-10000	0	225
ENAH	-0.03	0.036	0.14	15	-10000	0	15
EGFR	-0.009	0.007	0	194	-10000	0	194
EPHA2	-0.014	0.002	0	13	-10000	0	13
MYO6	-0.022	0.02	0.084	18	-10000	0	18
CTNNB1	-0.014	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.012	0.01	0	225	-10000	0	225
AQP5	-0.018	0.018	-10000	0	-10000	0	0
CTNND1	-0.014	0.002	0	10	-10000	0	10
mol:PI-4-5-P2	-0.021	0.02	0.084	17	-10000	0	17
regulation of calcium-dependent cell-cell adhesion	-0.022	0.02	0.084	18	-10000	0	18
EGF	-0.014	0.001	0	2	-10000	0	2
NCKAP1	-0.014	0	-10000	0	-10000	0	0
AQP3	-0.019	0.017	-10000	0	-10000	0	0
cortical microtubule organization	-0.021	0.004	0	18	-10000	0	18
GO:0000145	-0.02	0.018	0.077	17	-10000	0	17
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.021	0.004	0	18	-10000	0	18
MLLT4	-0.014	0	-10000	0	-10000	0	0
ARF6/GDP	-0.037	0.012	-10000	0	-10000	0	0
ARF6	-0.014	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.022	0.006	0	38	-10000	0	38
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.015	0.017	0.076	10	-10000	0	10
PVRL2	-0.014	0	-10000	0	-10000	0	0
ZYX	-0.017	0.018	0.084	11	-10000	0	11
ARF6/GTP	-0.025	0.007	-10000	0	-10000	0	0
CDH1	-0.014	0.002	0	8	-10000	0	8
EGFR/EGFR/EGF/EGF	-0.018	0.015	-10000	0	-10000	0	0
RhoA/GDP	-0.025	0.005	-10000	0	-10000	0	0
actin cytoskeleton organization	-0.024	0.019	0.075	18	-10000	0	18
IGF-1R heterotetramer	-0.014	0	-10000	0	-10000	0	0
GIT1	-0.014	0	-10000	0	-10000	0	0
IGF1R	-0.014	0	-10000	0	-10000	0	0
IGF1	-0.014	0.001	0	4	-10000	0	4
DIAPH1	-0.18	0.22	-10000	0	-0.44	222	222
Wnt receptor signaling pathway	0.021	0.004	-10000	0	0	18	18
RHOA	-0.014	0.001	0	2	-10000	0	2
RhoA/GTP	-0.037	0.012	-10000	0	-10000	0	0
CTNNA1	-0.014	0	-10000	0	-10000	0	0
VCL	-0.025	0.019	0.076	18	-10000	0	18
EFNA1	-0.014	0.003	0	24	-10000	0	24
LPP	-0.025	0.017	0.076	12	-10000	0	12
Ephrin A1/EPHA2	-0.027	0.008	-10000	0	-10000	0	0
SEC6/SEC8	-0.032	0.006	-10000	0	-10000	0	0
MGAT3	-0.022	0.02	0.084	18	-10000	0	18
HGF/MET	-0.028	0.007	-10000	0	-10000	0	0
HGF	-0.014	0.001	0	2	-10000	0	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.001	0.003	-10000	0	-10000	0	0
actin cable formation	-0.03	0.042	0.14	11	-10000	0	11
KIAA1543	-0.016	0.018	0.079	18	-10000	0	18
KIFC3	-0.022	0.02	0.084	18	-10000	0	18
NCK1	-0.014	0.002	0	11	-10000	0	11
EXOC3	-0.014	0	-10000	0	-10000	0	0
ACTN1	-0.021	0.018	0.084	12	-10000	0	12
NCK1/GIT1	-0.017	0.002	0	11	-10000	0	11
mol:GDP	-0.021	0.004	0	18	-10000	0	18
EXOC4	0	0	-10000	0	-10000	0	0
STX4	-0.022	0.02	0.084	18	-10000	0	18
PIP5K1C	-0.021	0.02	0.084	17	-10000	0	17
LIMA1	-0.002	0.005	0	453	-10000	0	453
ABI1	-0.014	0	-10000	0	-10000	0	0
ROCK1	-0.031	0.039	0.15	15	-10000	0	15
adherens junction assembly	-0.026	0.028	0.079	1	-0.14	19	20
IGF-1R heterotetramer/IGF1	-0.029	0.006	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.017	0	-10000	0	-10000	0	0
MET	-0.014	0.002	0	10	-10000	0	10
PLEKHA7	-0.02	0.004	0	18	-10000	0	18
mol:GTP	-0.022	0.006	0	38	-10000	0	38
establishment of epithelial cell apical/basal polarity	-0.033	0.018	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	-0.001	0.003	-10000	0	-10000	0	0
regulation of cell-cell adhesion	-0.024	0.019	0.075	18	-10000	0	18
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.001	0.003	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	-0.01	0.021	0.073	25	-10000	0	25
adherens junction organization	-0.004	0.019	0.097	10	-10000	0	10
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.053	0.081	205	-10000	0	205
FMN1	-0.005	0.014	0.063	10	-10000	0	10
mol:IP3	-0.011	0.022	0.079	24	-10000	0	24
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.006	0.014	0.062	9	-10000	0	9
CTNNB1	-0.015	0.001	-10000	0	-10000	0	0
AKT1	-0.017	0.011	0.047	7	-10000	0	7
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.006	0.006	-10000	0	-10000	0	0
CTNND1	-0.013	0.006	0.012	27	-10000	0	27
mol:PI-4-5-P2	-0.009	0.017	0.098	6	-10000	0	6
VASP	-0.009	0.017	0.073	13	-10000	0	13
ZYX	-0.007	0.016	0.071	14	-10000	0	14
JUB	-0.005	0.014	0.063	10	-10000	0	10
EGFR(dimer)	-0.004	0.018	0.1	7	-10000	0	7
E-cadherin/beta catenin-gamma catenin	-0.021	0.004	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.013	0.011	0.054	7	-10000	0	7
PIK3CA	-0.014	0.004	0.009	6	-10000	0	6
PI3K	-0.013	0.011	0.055	7	-10000	0	7
FYN	-0.013	0.02	0.068	25	-10000	0	25
mol:Ca2+	-0.011	0.022	0.078	24	-10000	0	24
JUP	-0.014	0.003	-10000	0	-10000	0	0
PIK3R1	-0.013	0.007	0.012	25	-10000	0	25
mol:DAG	-0.011	0.022	0.079	24	-10000	0	24
CDH1	-0.014	0.002	0	8	-10000	0	8
RhoA/GDP	0.018	0.053	0.081	205	-10000	0	205
establishment of polarity of embryonic epithelium	-0.009	0.017	0.098	6	-10000	0	6
SRC	-0.014	0	-10000	0	-10000	0	0
RAC1	-0.014	0	-10000	0	-10000	0	0
RHOA	-0.014	0.001	0	2	-10000	0	2
EGFR	-0.009	0.007	0	194	-10000	0	194
CASR	-0.015	0.022	0.072	25	-10000	0	25
RhoA/GTP	-0.014	0.022	0.068	30	-10000	0	30
AKT2	-0.017	0.011	0.047	7	-10000	0	7
actin cable formation	-0.009	0.016	0.097	6	-10000	0	6
apoptosis	0.009	0.021	-10000	0	-0.077	25	25
CTNNA1	-0.013	0.006	0.012	31	-10000	0	31
mol:GDP	-0.01	0.018	0.075	12	-10000	0	12
PIP5K1A	-0.009	0.017	0.071	14	-10000	0	14
PLCG1	-0.012	0.022	0.08	24	-10000	0	24
Rac1/GTP	-0.006	0.018	0.091	7	-10000	0	7
homophilic cell adhesion	-0.001	0.001	0.007	1	-10000	0	1

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.014	0.002	0	4	-10000	0	4
RAS family/GTP	0.001	0.038	0.1	11	-10000	0	11
NFATC4	-0.023	0.021	-10000	0	-10000	0	0
ERBB2IP	-0.013	0.003	0	31	-10000	0	31
HSP90 (dimer)	-0.014	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.007	0.037	0.063	106	-10000	0	106
JUN	0.013	0.063	0.12	103	-10000	0	103
HRAS	-0.013	0.003	0.008	6	-10000	0	6
DOCK7	-0.016	0.02	0.069	7	-10000	0	7
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.012	0.021	-10000	0	-10000	0	0
AKT1	-0.009	0.001	0	4	-10000	0	4
BAD	-0.014	0.001	0	4	-10000	0	4
MAPK10	-0.01	0.016	-10000	0	-10000	0	0
mol:GTP	0	0.001	0.004	4	-0.003	1	5
ErbB2/ErbB3/neuregulin 1 beta	-0.007	0.04	0.069	106	-10000	0	106
RAF1	0.022	0.063	0.15	51	-10000	0	51
ErbB2/ErbB3/neuregulin 2	-0.019	0.009	-10000	0	-10000	0	0
STAT3	0.009	0.004	-10000	0	-10000	0	0
cell migration	-0.01	0.017	-10000	0	-0.074	1	1
mol:PI-3-4-5-P3	-0.001	0	-10000	0	-10000	0	0
cell proliferation	0.037	0.12	0.37	5	-0.51	5	10
FOS	0.052	0.13	0.28	118	-0.3	7	125
NRAS	-0.01	0.006	0	139	-10000	0	139
mol:Ca2+	-0.007	0.037	0.063	106	-10000	0	106
MAPK3	0.036	0.089	0.32	5	-10000	0	5
MAPK1	0.025	0.12	0.32	5	-0.44	15	20
JAK2	-0.017	0.026	0.071	7	-10000	0	7
NF2	-0.003	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.008	0.008	-10000	0	-0.05	5	5
NRG1	-0.014	0.003	0.012	6	-10000	0	6
GRB2/SOS1	-0.005	0.007	0.008	128	-10000	0	128
MAPK8	-0.02	0.044	0.074	1	-0.13	55	56
MAPK9	-0.02	0.016	-10000	0	-10000	0	0
ERBB2	-0.013	0.003	0	31	-10000	0	31
ERBB3	-0.012	0.006	0.014	2	-10000	0	2
SHC1	-0.013	0.004	0.001	49	-10000	0	49
RAC1	-0.014	0	-10000	0	-10000	0	0
apoptosis	0.009	0.01	-10000	0	-0.12	3	3
STAT3 (dimer)	0.01	0.006	-10000	0	-10000	0	0
RNF41	-0.018	0.002	0	4	-10000	0	4
FRAP1	-0.014	0.002	0	5	-10000	0	5
RAC1-CDC42/GTP	-0.021	0.018	0.021	1	-0.055	1	2
ErbB2/ErbB2/HSP90 (dimer)	-0.019	0.005	-10000	0	-0.037	31	31
CHRNA1	0.032	0.091	0.27	10	-0.29	5	15
myelination	-0.027	0.02	-10000	0	-10000	0	0
PPP3CB	-0.016	0.025	0.067	7	-10000	0	7
KRAS	-0.013	0.003	0.004	13	-10000	0	13
RAC1-CDC42/GDP	-0.013	0.031	0.055	63	-10000	0	63
NRG2	-0.014	0	-10000	0	-10000	0	0
mol:GDP	-0.008	0.008	-10000	0	-0.05	5	5
SOS1	0	0.001	0.006	1	-10000	0	1
MAP2K2	0.019	0.064	0.16	37	-10000	0	37
SRC	-0.014	0	-10000	0	-10000	0	0
mol:cAMP	-0.001	0	-10000	0	-10000	0	0
PTPN11	-0.021	0.023	0.072	4	-10000	0	4
MAP2K1	0.023	0.13	0.31	5	-0.56	13	18
heart morphogenesis	-0.007	0.037	0.063	106	-10000	0	106
RAS family/GDP	-0.004	0.033	0.082	10	-10000	0	10
GRB2	-0.014	0.002	0.002	6	-10000	0	6
PRKACA	0.003	0.002	-10000	0	-10000	0	0
CHRNE	0.001	0.018	0.04	33	-10000	0	33
HSP90AA1	-0.014	0	-10000	0	-10000	0	0
activation of caspase activity	0.009	0.001	-10000	0	0	4	4
nervous system development	-0.007	0.037	0.063	106	-10000	0	106
CDC42	-0.014	0	-10000	0	-10000	0	0

×

IL4-mediated signaling events

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
BCL2L1	0.053	0.25	0.6	10	-10000	0	10
STAT6 (cleaved dimer)	-0.034	0.16	-10000	0	-10000	0	0
IGHG1	0.05	0.15	0.36	43	-0.44	1	44
IGHG3	0.047	0.23	0.53	11	-10000	0	11
AKT1	0.025	0.17	0.4	13	-0.64	3	16
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	0.034	0.13	0.36	14	-10000	0	14
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	0.039	0.17	0.39	17	-0.57	3	20
THY1	-0.079	0.43	0.6	9	-0.89	55	64
MYB	-0.014	0.002	0	8	-10000	0	8
HMGA1	-0.014	0.001	0	1	-10000	0	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	0.047	0.19	0.41	42	-10000	0	42
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	0.039	0.17	0.4	16	-0.57	3	19
SP1	0.06	0.078	0.14	261	-0.12	4	265
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	-0.011	0.024	-10000	0	-0.053	22	22
STAT6 (dimer)/ETS1	0.031	0.22	0.49	9	-10000	0	9
SOCS1	0.026	0.19	0.37	31	-10000	0	31
SOCS3	0.033	0.16	0.42	8	-10000	0	8
FCER2	0.051	0.22	0.55	15	-10000	0	15
PARP14	0	0.001	0.022	1	-10000	0	1
CCL17	0.053	0.25	0.6	10	-10000	0	10
GRB2	-0.014	0.001	0	5	-10000	0	5
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	0.04	0.15	0.35	33	-10000	0	33
T cell proliferation	0.036	0.23	0.53	9	-10000	0	9
IL4R/JAK1	0.04	0.24	0.53	12	-10000	0	12
EGR2	0.057	0.26	0.65	15	-10000	0	15
JAK2	0.014	0.047	0.1	45	-10000	0	45
JAK3	-0.015	0.006	0.051	1	-10000	0	1
PIK3R1	-0.013	0.004	0	36	-10000	0	36
JAK1	0.007	0.026	0.058	44	-10000	0	44
COL1A2	0.12	0.21	0.38	128	-0.9	4	132
CCL26	0.055	0.25	0.56	15	-10000	0	15
IL4R	0.062	0.27	0.67	15	-10000	0	15
PTPN6	-0.013	0.019	-10000	0	-0.051	11	11
IL13RA2	0.1	0.28	0.63	34	-10000	0	34
IL13RA1	0.008	0.043	0.082	72	-10000	0	72
IRF4	0.03	0.093	0.35	2	-10000	0	2
ARG1	0.039	0.13	0.42	13	-10000	0	13
CBL	0.037	0.17	0.37	30	-10000	0	30
GTF3A	0.004	0.051	0.14	66	-10000	0	66
PIK3CA	-0.014	0.003	0	25	-10000	0	25
IL13RA1/JAK2	0.021	0.066	0.14	75	-10000	0	75
IRF4/BCL6	0.024	0.082	-10000	0	-10000	0	0
CD40LG	-0.015	0.008	0.16	1	-10000	0	1
MAPK14	0.036	0.17	0.41	16	-10000	0	16
mitosis	0.025	0.16	0.39	14	-0.61	3	17
STAT6	0.079	0.28	0.63	30	-10000	0	30
SPI1	-0.015	0.002	-10000	0	-10000	0	0
RPS6KB1	0.02	0.16	0.38	13	-0.59	3	16
STAT6 (dimer)	0.079	0.27	0.63	30	-10000	0	30
STAT6 (dimer)/PARP14	-0.056	0.16	-10000	0	-10000	0	0
mast cell activation	-0.004	0.013	-10000	0	-0.033	44	44
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	0.037	0.16	0.39	14	-10000	0	14
FRAP1	0.024	0.17	0.4	13	-0.64	3	16
LTA	0.053	0.25	0.6	10	-10000	0	10
FES	-0.014	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	-0.069	0.28	-10000	0	-0.6	42	42
CCL11	0.047	0.23	0.54	11	-10000	0	11
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	0.038	0.16	0.39	14	-10000	0	14
IL2RG	-0.015	0.006	-10000	0	-10000	0	0
IL10	0.053	0.25	0.59	11	-10000	0	11
IRS1	-0.014	0.001	0	5	-10000	0	5
IRS2	-0.014	0.002	0	11	-10000	0	11
IL4	0.045	0.13	0.42	11	-10000	0	11
IL5	0.053	0.25	0.6	10	-10000	0	10
IL4/IL4R/JAK1/IL13RA1/JAK2	0.067	0.25	0.55	42	-10000	0	42
COL1A1	0.073	0.19	0.49	62	-10000	0	62
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	0.036	0.23	0.53	8	-10000	0	8
IL2R gamma/JAK3	-0.017	0.005	-10000	0	-10000	0	0
TFF3	0.055	0.25	0.63	11	-10000	0	11
ALOX15	0.053	0.25	0.59	11	-10000	0	11
MYBL1	-0.012	0.005	0	80	-10000	0	80
T-helper 2 cell differentiation	0.048	0.23	0.51	17	-10000	0	17
SHC1	-0.013	0.004	0	46	-10000	0	46
CEBPB	-0.015	0.002	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	0.035	0.16	0.35	31	-0.58	3	34
mol:PI-3-4-5-P3	0.025	0.17	0.4	13	-0.64	3	16
PI3K	0.024	0.17	0.4	13	-0.67	3	16
DOK2	0	0	-10000	0	-10000	0	0
ETS1	-0.015	0.028	-10000	0	-0.067	45	45
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	0.036	0.15	0.34	33	-10000	0	33
ITGB3	0.053	0.25	0.6	10	-10000	0	10
PIGR	0.053	0.25	0.61	11	-10000	0	11
IGHE	-0.028	0.048	-10000	0	-0.11	70	70
MAPKKK cascade	0.037	0.14	0.32	44	-10000	0	44
BCL6	-0.014	0.003	-10000	0	-0.054	1	1
OPRM1	0.053	0.25	0.6	10	-10000	0	10
RETNLB	0.055	0.25	0.56	15	-10000	0	15
SELP	0.053	0.25	0.61	10	-10000	0	10
AICDA	0.046	0.23	0.55	8	-10000	0	8

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	-0.014	0.003	0	22	-9999	22
EPHB2	-0.013	0.006	0.011	32	-9999	32
EFNB1	-0.003	0.007	0	433	-9999	433
mol:GTP	0	0	-10000	0	-9999	0
Rac1/GDP	-0.005	0.012	-10000	0	-9999	0
Ephrin B2/EPHB1-2	-0.013	0.012	0.02	54	-9999	54
neuron projection morphogenesis	-0.005	0.011	0.018	2	-9999	2
Ephrin B1/EPHB1-2/Tiam1	-0.004	0.011	-10000	0	-9999	0
DNM1	-0.002	0.006	0	439	-9999	439
cell-cell signaling	0	0.001	0.007	2	-9999	2
MAP2K4	-0.005	0.01	-10000	0	-9999	0
YES1	0.004	0.004	-10000	0	-9999	0
Ephrin B1/EPHB1-2/NCK2	-0.004	0.011	-10000	0	-9999	0
PI3K	0.013	0.014	-10000	0	-9999	0
mol:GDP	-0.004	0.011	-10000	0	-9999	0
ITGA2B	-0.014	0	-10000	0	-9999	0
endothelial cell proliferation	-0.011	0.008	0.013	43	-9999	43
FYN	0.004	0.004	-10000	0	-9999	0
MAP3K7	-0.002	0.006	0.12	1	-9999	1
FGR	0.001	0.004	-10000	0	-9999	0
TIAM1	-0.014	0.003	0	21	-9999	21
PIK3R1	-0.013	0.004	0	36	-9999	36
RGS3	-0.014	0.001	0	1	-9999	1
cell adhesion	-0.01	0.015	-10000	0	-9999	0
LYN	0.004	0.004	-10000	0	-9999	0
Ephrin B1/EPHB1-2/Src Family Kinases	0.002	0.003	-10000	0	-9999	0
Ephrin B1/EPHB1-2	0.001	0.001	-10000	0	-9999	0
SRC	0.001	0.004	-10000	0	-9999	0
ITGB3	-0.014	0	-10000	0	-9999	0
EPHB1	-0.013	0.005	0.007	31	-9999	31
EPHB4	-0.014	0	-10000	0	-9999	0
RAC1	-0.014	0	-10000	0	-9999	0
Ephrin B2/EPHB4	-0.011	0.008	0.013	43	-9999	43
alphaIIb/beta3 Integrin	-0.017	0	-10000	0	-9999	0
BLK	0.004	0.004	-10000	0	-9999	0
HCK	0.004	0.004	-10000	0	-9999	0
regulation of stress fiber formation	0.004	0.011	-10000	0	-9999	0
MAPK8	-0.008	0.012	-10000	0	-9999	0
Ephrin B1/EPHB1-2/RGS3	-0.004	0.011	-10000	0	-9999	0
endothelial cell migration	-0.005	0.01	-10000	0	-9999	0
NCK2	-0.014	0.001	0	1	-9999	1
PTPN13	-0.01	0.004	-10000	0	-9999	0
regulation of focal adhesion formation	0.004	0.011	-10000	0	-9999	0
chemotaxis	0.004	0.011	-10000	0	-9999	0
PIK3CA	-0.014	0.003	0	25	-9999	25
Rac1/GTP	-0.005	0.012	0.022	4	-9999	4
angiogenesis	0.001	0.004	-10000	0	-9999	0
LCK	0.001	0.004	-10000	0	-9999	0

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.01	0.012	0.031	7	-10000	0	7
PDGFRB	-0.014	0.007	0.012	30	-10000	0	30
SPHK1	-0.006	0.009	-10000	0	-10000	0	0
mol:S1P	-0.008	0.023	0.18	1	-10000	0	1
S1P1/S1P/Gi	-0.042	0.059	0.16	13	-0.27	3	16
GNAO1	-0.001	0.004	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/PLCgamma1	-0.059	0.062	0.16	16	-0.18	3	19
PLCG1	-0.051	0.064	0.16	15	-0.16	47	62
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.014	0.007	0.012	30	-10000	0	30
GNAI2	-0.012	0.011	0.03	34	-10000	0	34
GNAI3	-0.011	0.009	0.021	26	-10000	0	26
GNAI1	-0.011	0.009	0.021	28	-10000	0	28
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	0.045	0.062	0.1	280	-10000	0	280
S1P1/S1P	0.032	0.057	0.17	28	-10000	0	28
negative regulation of cAMP metabolic process	-0.041	0.061	0.16	15	-0.2	7	22
MAPK3	-0.055	0.072	0.21	15	-0.24	3	18
calcium-dependent phospholipase C activity	0	0.002	0.009	28	-10000	0	28
Rac1/GDP	-0.009	0	-10000	0	-10000	0	0
RhoA/GDP	-0.009	0.001	0	2	-10000	0	2
KDR	-0.016	0.008	-10000	0	-10000	0	0
PLCB2	0.033	0.06	0.17	36	-10000	0	36
RAC1	-0.014	0	-10000	0	-10000	0	0
RhoA/GTP	-0.01	0.018	0.075	2	-10000	0	2
receptor internalization	0.029	0.054	0.16	25	-10000	0	25
PTGS2	-0.066	0.078	0.26	15	-10000	0	15
Rac1/GTP	-0.01	0.018	0.075	2	-10000	0	2
RHOA	-0.014	0.001	0	2	-10000	0	2
VEGFA	-0.008	0.009	-10000	0	-10000	0	0
negative regulation of T cell proliferation	-0.041	0.061	0.16	15	-0.2	7	22
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	-0.011	0.008	0.022	19	-10000	0	19
MAPK1	-0.052	0.071	0.21	15	-0.24	3	18
S1P1/S1P/PDGFB-D/PDGFRB	0.038	0.068	0.15	69	-10000	0	69
ABCC1	-0.014	0.007	0.01	37	-10000	0	37

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	-0.011	0.006	0	126	-10000	0	126
SMAD2	-0.011	0.018	-10000	0	-0.11	6	6
SMAD3	-0.005	0.018	0.06	38	-10000	0	38
SMAD3/SMAD4	-0.002	0.009	-10000	0	-10000	0	0
SMAD4/Ubc9/PIASy	-0.015	0.009	0	126	-10000	0	126
SMAD2/SMAD2/SMAD4	-0.022	0.018	-10000	0	-0.1	5	5
PPM1A	-0.014	0	-10000	0	-10000	0	0
CALM1	-0.013	0.003	0	27	-10000	0	27
SMAD2/SMAD4	-0.012	0.016	-10000	0	-0.1	5	5
MAP3K1	-0.014	0.001	0	1	-10000	0	1
TRAP-1/SMAD4	-0.013	0.007	0	126	-10000	0	126
MAPK3	-0.014	0	-10000	0	-10000	0	0
MAPK1	-0.014	0.003	0	17	-10000	0	17
NUP214	-0.014	0	-10000	0	-10000	0	0
CTDSP1	-0.014	0.001	0	3	-10000	0	3
CTDSP2	-0.013	0.004	0	37	-10000	0	37
CTDSPL	-0.014	0	-10000	0	-10000	0	0
KPNB1	-0.014	0	-10000	0	-10000	0	0
TGFBRAP1	-0.014	0	-10000	0	-10000	0	0
UBE2I	-0.014	0	-10000	0	-10000	0	0
NUP153	-0.014	0.001	0	3	-10000	0	3
KPNA2	-0.014	0.002	0	12	-10000	0	12
PIAS4	-0.014	0	-10000	0	-10000	0	0

×

Signaling mediated by 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.Total.Perturbations
PTGS2	0.002	0.062	0.26	29	-9999	29
MKNK1	-0.014	0	-10000	0	-9999	0
MAPK14	-0.014	0.029	0.11	30	-9999	30
ATF2/c-Jun	-0.011	0.02	0.071	29	-9999	29
MAPK11	-0.014	0.029	0.11	30	-9999	30
MITF	-0.005	0.032	0.12	30	-9999	30
MAPKAPK5	-0.005	0.032	0.12	30	-9999	30
KRT8	-0.004	0.036	0.14	30	-9999	30
MAPKAPK3	-0.014	0.001	0	2	-9999	2
MAPKAPK2	-0.014	0	-10000	0	-9999	0
p38alpha-beta/CK2	-0.015	0.044	0.16	30	-9999	30
CEBPB	-0.004	0.037	0.14	30	-9999	30
SLC9A1	-0.005	0.032	0.12	30	-9999	30
mol:GDP	0	0	-10000	0	-9999	0
ATF2	-0.007	0.034	0.13	30	-9999	30
p38alpha-beta/MNK1	-0.016	0.04	0.15	30	-9999	30
JUN	-0.011	0.02	0.07	29	-9999	29
PPARGC1A	-0.005	0.033	0.13	30	-9999	30
USF1	-0.002	0.031	0.12	30	-9999	30
RAB5/GDP/GDI1	-0.012	0.02	0.073	22	-9999	22
NOS2	-0.002	0.031	0.12	30	-9999	30
DDIT3	-0.003	0.036	0.14	30	-9999	30
RAB5A	-0.014	0	-10000	0	-9999	0
HSPB1	-0.008	0.032	0.1	39	-9999	39
p38alpha-beta/HBP1	-0.016	0.04	0.15	30	-9999	30
CREB1	0.001	0.031	0.13	29	-9999	29
RAB5/GDP	-0.009	0	-10000	0	-9999	0
EIF4E	-0.02	0.028	0.092	31	-9999	31
RPS6KA4	-0.005	0.032	0.12	30	-9999	30
PLA2G4A	-0.018	0.021	0.091	12	-9999	12
GDI1	-0.006	0.027	0.12	22	-9999	22
TP53	-0.008	0.04	0.15	30	-9999	30
RPS6KA5	-0.005	0.032	0.12	30	-9999	30
ESR1	-0.005	0.032	0.12	30	-9999	30
HBP1	-0.014	0	-10000	0	-9999	0
MEF2C	-0.005	0.027	0.12	21	-9999	21
MEF2A	-0.005	0.032	0.12	30	-9999	30
EIF4EBP1	-0.001	0.017	0.13	8	-9999	8
KRT19	-0.004	0.036	0.14	30	-9999	30
ELK4	-0.005	0.032	0.12	30	-9999	30
ATF6	-0.005	0.032	0.12	30	-9999	30
ATF1	0	0.028	0.13	24	-9999	24
p38alpha-beta/MAPKAPK2	-0.016	0.04	0.15	30	-9999	30
p38alpha-beta/MAPKAPK3	-0.016	0.04	0.15	30	-9999	30

×

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

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
BAG4	-0.014	0	-10000	0	-10000	0	0
Caspase 8 (4 units)	-0.01	0.024	0.052	64	-0.068	4	68
NEF	-0.005	0	-10000	0	-10000	0	0
NFKBIA	-0.013	0.021	0.069	32	-10000	0	32
BIRC3	-0.028	0.011	0.087	3	-10000	0	3
CYCS	-0.012	0.025	0.09	12	-10000	0	12
RIPK1	-0.014	0.002	0	9	-10000	0	9
CD247	-0.019	0.001	-10000	0	-10000	0	0
MAP2K7	0.008	0.024	-10000	0	-10000	0	0
protein ubiquitination	0	0.035	0.12	23	-10000	0	23
CRADD	-0.014	0	-10000	0	-10000	0	0
DAXX	-0.014	0.001	0	1	-10000	0	1
FAS	-0.012	0.005	0	68	-10000	0	68
BID	-0.015	0.008	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	-0.027	0.007	0	36	-10000	0	36
TRADD	-0.014	0	-10000	0	-10000	0	0
MAP3K5	-0.014	0.001	0	4	-10000	0	4
CFLAR	-0.014	0.001	0	5	-10000	0	5
FADD	-0.014	0.001	0	2	-10000	0	2
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.027	0.007	0	36	-10000	0	36
MAPK8	0.003	0.023	-10000	0	-10000	0	0
APAF1	-0.014	0	-10000	0	-10000	0	0
TRAF1	-0.014	0.001	0	1	-10000	0	1
TRAF2	-0.014	0	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.011	0.008	-10000	0	-10000	0	0
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.004	0.029	0.089	18	-10000	0	18
CHUK	0	0.036	0.12	23	-10000	0	23
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.023	0.01	-10000	0	-10000	0	0
TCRz/NEF	-0.016	0.001	0	2	-10000	0	2
TNF	-0.014	0.001	0	2	-10000	0	2
FASLG	-0.018	0.001	0	2	-10000	0	2
NFKB1	-0.012	0.021	0.069	32	-10000	0	32
TNFR1A/BAG4/TNF-alpha	-0.013	0.01	0	185	-10000	0	185
CASP6	0.002	0.018	-10000	0	-10000	0	0
CASP7	-0.002	0.071	0.24	36	-10000	0	36
RELA	-0.012	0.021	0.069	33	-10000	0	33
CASP2	-0.014	0.001	0	1	-10000	0	1
CASP3	0	0.07	0.24	35	-10000	0	35
TNFRSF1A	-0.009	0.007	0	183	-10000	0	183
TNFR1A/BAG4	-0.011	0.008	0	183	-10000	0	183
CASP8	-0.014	0.002	0	10	-10000	0	10
CASP9	-0.014	0.001	0	4	-10000	0	4
MAP3K14	0.005	0.038	0.12	27	-10000	0	27
APAF-1/Caspase 9	-0.034	0.024	0.047	2	-10000	0	2
BCL2	-0.002	0.022	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	-0.013	0.002	0	9	-10000	0	9
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	-0.014	0.002	0	9	-10000	0	9
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	-0.014	0.003	0	21	-10000	0	21
RAC1-CDC42/GTP/PAK family	-0.001	0.002	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
YES1	-0.012	0.005	0	79	-10000	0	79
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	-0.014	0	-10000	0	-10000	0	0
FYN	-0.014	0.003	0	21	-10000	0	21
MAP3K12	-0.014	0	-10000	0	-10000	0	0
FGR	-0.014	0.003	0	17	-10000	0	17
p38 alpha/TAB1	-0.02	0.043	0.087	6	-0.15	16	22
PRKG1	-0.014	0	-10000	0	-10000	0	0
DUSP8	-0.011	0.006	0	130	-10000	0	130
PGK/cGMP/p38 alpha	-0.021	0.04	0.073	4	-0.15	16	20
apoptosis	-0.02	0.041	0.083	6	-0.15	16	22
RAL/GTP	-0.012	0.004	0	46	-10000	0	46
LYN	-0.012	0.005	0	64	-10000	0	64
DUSP1	-0.014	0.003	0	18	-10000	0	18
PAK1	-0.014	0	-10000	0	-10000	0	0
SRC	-0.014	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.018	0	-10000	0	-10000	0	0
TRAF6	-0.014	0	-10000	0	-10000	0	0
RAC1	-0.014	0	-10000	0	-10000	0	0
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	0	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.014	0	-10000	0	-10000	0	0
MAPK11	-0.021	0.041	0.096	8	-0.14	14	22
BLK	-0.014	0	-10000	0	-10000	0	0
HCK	-0.012	0.005	0	86	-10000	0	86
MAP2K3	-0.014	0	-10000	0	-10000	0	0
DUSP16	0	0	-10000	0	-10000	0	0
DUSP10	-0.014	0.002	0	7	-10000	0	7
TRAF6/MEKK3	-0.012	0	-10000	0	-10000	0	0
MAP3K7IP1	-0.014	0	-10000	0	-10000	0	0
MAPK14	-0.019	0.044	0.093	6	-0.16	16	22
positive regulation of innate immune response	-0.027	0.05	0.11	7	-0.16	20	27
LCK	-0.014	0.001	0	4	-10000	0	4
p38alpha-beta/MKP7	-0.028	0.047	0.1	7	-0.16	20	27
p38alpha-beta/MKP5	-0.029	0.051	0.11	7	-0.16	20	27
PGK/cGMP	-0.009	0	-10000	0	-10000	0	0
PAK2	-0.014	0.003	0	24	-10000	0	24
p38alpha-beta/MKP1	-0.029	0.05	0.1	6	-0.16	20	26
CDC42	-0.014	0	-10000	0	-10000	0	0
RALB	-0.014	0.001	0	1	-10000	0	1
RALA	-0.013	0.004	0	45	-10000	0	45
PAK3	-0.002	0.005	0	450	-10000	0	450

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	-0.014	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.008	0.005	-10000	0	-10000	0	0
NT3 (dimer)/TRKC	-0.017	0.003	0	8	-10000	0	8
NT3 (dimer)/TRKB	-0.017	0.007	0	38	-10000	0	38
SHC/Grb2/SOS1/GAB1/PI3K	-0.007	0.004	-10000	0	-10000	0	0
RAPGEF1	-0.014	0	-10000	0	-10000	0	0
BDNF	-0.004	0.006	0	192	-10000	0	192
PIK3CA	-0.014	0.003	0	11	-10000	0	11
DYNLT1	-0.012	0.005	0	34	-10000	0	34
NTRK1	-0.014	0.001	0	1	-10000	0	1
NTRK2	-0.013	0.005	0	31	-10000	0	31
NTRK3	-0.014	0.002	0	8	-10000	0	8
NT-4/5 (dimer)/TRKB	-0.012	0.005	0	38	-10000	0	38
neuron apoptosis	0.059	0.046	0.14	38	-0.085	2	40
SHC 2-3/Grb2	-0.062	0.049	0.089	2	-0.15	38	40
SHC1	-0.013	0.004	0	25	-10000	0	25
SHC2	-0.047	0.043	-10000	0	-10000	0	0
SHC3	-0.045	0.051	-10000	0	-0.3	3	3
STAT3 (dimer)	-0.016	0.008	0	52	-10000	0	52
NT3 (dimer)/TRKA	-0.02	0.004	0	9	-10000	0	9
RIN/GDP	-0.012	0.023	0.061	1	-0.17	3	4
GIPC1	-0.014	0	-10000	0	-10000	0	0
KRAS	-0.014	0.002	0	4	-10000	0	4
DNAJA3	-0.008	0.011	0.046	10	-10000	0	10
RIN/GTP	-0.005	0.004	0	116	-10000	0	116
CCND1	-0.014	0.007	0	52	-10000	0	52
MAGED1	-0.014	0.001	0	2	-10000	0	2
PTPN11	-0.014	0	-10000	0	-10000	0	0
RICS	-0.01	0.006	0	78	-10000	0	78
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.012	0.004	0	28	-10000	0	28
GRB2	-0.014	0.001	0	3	-10000	0	3
NGF (dimer)/TRKA/MATK	-0.013	0.001	0	1	-10000	0	1
TRKA/NEDD4-2	-0.017	0.001	0	1	-10000	0	1
ELMO1	-0.009	0.007	0	97	-10000	0	97
RhoG/GTP/ELMO1/DOCK1	-0.009	0.006	0	97	-10000	0	97
NGF	0	0	-10000	0	-10000	0	0
HRAS	-0.014	0	-10000	0	-10000	0	0
DOCK1	-0.014	0	-10000	0	-10000	0	0
GAB2	-0.014	0.001	0	2	-10000	0	2
RIT2	-0.008	0.007	0	116	-10000	0	116
RIT1	-0.01	0.006	0	79	-10000	0	79
FRS2	-0.014	0.001	0	3	-10000	0	3
DNM1	-0.002	0.005	0	225	-10000	0	225
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.014	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.004	0.014	0.052	14	-10000	0	14
mol:GDP	-0.026	0.041	0.076	2	-0.16	11	13
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	-0.005	0.004	0	97	-10000	0	97
RIT1/GDP	-0.018	0.027	-10000	0	-0.14	6	6
TIAM1	-0.014	0.003	0	12	-10000	0	12
PIK3R1	-0.013	0.004	0	22	-10000	0	22
BDNF (dimer)/TRKB	-0.004	0.008	0	214	-10000	0	214
KIDINS220/CRKL/C3G	-0.017	0	-10000	0	-10000	0	0
SHC/RasGAP	-0.015	0.005	0	30	-10000	0	30
FRS2 family/SHP2	-0.02	0.002	0	3	-10000	0	3
SHC/GRB2/SOS1/GAB1	-0.016	0.006	0	30	-10000	0	30
RIT1/GTP	-0.006	0.004	0	79	-10000	0	79
NT3 (dimer)	-0.014	0	-10000	0	-10000	0	0
RAP1/GDP	-0.021	0.024	-10000	0	-0.1	12	12
KIDINS220/CRKL	-0.014	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.004	0.006	0	192	-10000	0	192
ubiquitin-dependent protein catabolic process	-0.013	0.001	0	1	-10000	0	1
Schwann cell development	-0.002	0.004	-10000	0	-10000	0	0
EHD4	-0.013	0.004	0	21	-10000	0	21
FRS2 family/GRB2/SOS1	-0.017	0.003	0	6	-10000	0	6
FRS2 family/SHP2/CRK family/C3G/GAB2	-0.01	0.008	0.049	4	-0.072	1	5
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	-0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.005	0.012	-10000	0	-10000	0	0
ABL1	-0.014	0.001	0	2	-10000	0	2
SH2B family/GRB2/SOS1	-0.008	0.001	0	3	-10000	0	3
Rap1/GTP	-0.002	0.005	-10000	0	-10000	0	0
STAT3	-0.016	0.008	0	52	-10000	0	52
axon guidance	-0.005	0.012	-10000	0	-10000	0	0
MAPK3	-0.017	0.007	0.097	1	-10000	0	1
MAPK1	-0.017	0.008	0.097	1	-10000	0	1
CDC42/GDP	-0.022	0.031	0.061	2	-0.12	11	13
NTF3	-0.014	0	-10000	0	-10000	0	0
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	-0.013	0.002	0	5	-10000	0	5
PI3K	-0.015	0.006	0	32	-10000	0	32
FRS3	-0.014	0	-10000	0	-10000	0	0
FAIM	-0.014	0.002	0	4	-10000	0	4
GAB1	-0.014	0.001	0	2	-10000	0	2
RASGRF1	-0.008	0.011	0.046	10	-10000	0	10
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.017	0.007	-10000	0	-10000	0	0
RGS19	-0.014	0	-10000	0	-10000	0	0
CDC42	-0.014	0	-10000	0	-10000	0	0
RAS family/GTP	0.002	0.044	0.11	2	-0.28	4	6
Rac1/GDP	-0.022	0.031	0.059	3	-0.12	11	14
NGF (dimer)/TRKA/GRIT	-0.01	0.006	0	79	-10000	0	79
neuron projection morphogenesis	0.011	0.026	-10000	0	-10000	0	0
NGF (dimer)/TRKA/NEDD4-2	-0.013	0.001	0	1	-10000	0	1
MAP2K1	-0.01	0.034	0.091	27	-10000	0	27
NGFR	-0.014	0.002	0	8	-10000	0	8
NGF (dimer)/TRKA/GIPC/GAIP	-0.001	0.003	-10000	0	-10000	0	0
RAS family/GTP/PI3K	-0.006	0.004	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	-0.021	0.003	0	6	-10000	0	6
NRAS	-0.011	0.006	0	67	-10000	0	67
GRB2/SOS1	-0.008	0.001	0	3	-10000	0	3
PRKCI	-0.014	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	-0.014	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	0	0.007	-10000	0	-10000	0	0
RASA1	-0.014	0.002	0	5	-10000	0	5
TRKA/c-Abl	-0.017	0.002	0	3	-10000	0	3
SQSTM1	-0.014	0.001	0	1	-10000	0	1
BDNF (dimer)/TRKB/GIPC	-0.005	0.01	0	212	-10000	0	212
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.016	0.001	0	2	-10000	0	2
MATK	-0.014	0	-10000	0	-10000	0	0
NEDD4L	-0.014	0	-10000	0	-10000	0	0
RAS family/GDP	-0.02	0.02	-10000	0	-0.071	25	25
NGF (dimer)/TRKA	-0.006	0.002	-10000	0	-10000	0	0
Rac1/GTP	-0.012	0.013	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family	-0.027	0.003	-10000	0	-10000	0	0

×

Syndecan-3-mediated signaling events

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
CTTN	-0.014	0	-9999	0	-10000	0	0
Syndecan-3/Src/Cortactin	-0.023	0.054	-9999	0	-0.29	18	18
Syndecan-3/Neurocan	-0.016	0.053	-9999	0	-0.29	18	18
POMC	-0.014	0	-9999	0	-10000	0	0
EGFR	-0.009	0.007	0	194	-10000	0	194
Syndecan-3/EGFR	-0.016	0.062	-9999	0	-0.33	19	19
AGRP	-0.014	0	-9999	0	-10000	0	0
NCSTN	-0.013	0.003	0	30	-10000	0	30
PSENEN	-0.014	0.001	0	1	-10000	0	1
RP11-540L11.1	0	0	-9999	0	-10000	0	0
APH1B	-0.014	0	-9999	0	-10000	0	0
APH1A	-0.014	0.002	0	10	-10000	0	10
NCAN	-0.012	0.005	0	91	-10000	0	91
long-term memory	-0.021	0.055	-9999	0	-0.29	19	19
Syndecan-3/IL8	-0.016	0.058	-9999	0	-0.3	19	19
PSEN1	-0.014	0.001	0	1	-10000	0	1
Src/Cortactin	-0.017	0	-9999	0	-10000	0	0
FYN	-0.014	0.003	0	21	-10000	0	21
limb bud formation	-0.015	0.06	-9999	0	-0.37	15	15
MC4R	-0.014	0.001	0	1	-10000	0	1
SRC	-0.014	0	-9999	0	-10000	0	0
PTN	-0.014	0.003	0	26	-10000	0	26
FGFR/FGF/Syndecan-3	-0.015	0.061	-9999	0	-0.37	15	15
neuron projection morphogenesis	-0.025	0.043	-9999	0	-0.24	18	18
Syndecan-3/AgRP	-0.019	0.063	-9999	0	-0.34	19	19
Syndecan-3/AgRP/MC4R	-0.021	0.062	-9999	0	-0.33	19	19
Fyn/Cortactin	-0.016	0.003	0	21	-10000	0	21
SDC3	-0.015	0.061	-9999	0	-0.37	15	15
GO:0007205	0	0	-9999	0	-10000	0	0
positive regulation of leukocyte migration	-0.016	0.057	-9999	0	-0.3	19	19
IL8	-0.011	0.006	0	115	-10000	0	115
Syndecan-3/Fyn/Cortactin	-0.02	0.057	-9999	0	-0.31	18	18
Syndecan-3/CASK	-0.016	0.061	-9999	0	-0.33	19	19
alpha-MSH/MC4R	-0.017	0.001	0	1	-10000	0	1
Gamma Secretase	-0.025	0.007	-9999	0	-10000	0	0

×

Arf6 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
CENTA1/KIF3B	-0.007	0	0	2	-10000	0	2
ARNO/beta Arrestin1-2	-0.013	0.001	0	1	-10000	0	1
EGFR	-0.009	0.007	0	194	-10000	0	194
EPHA2	-0.014	0.002	0	13	-10000	0	13
USP6	-0.014	0	-10000	0	-10000	0	0
IQSEC1	-0.014	0.002	0	9	-10000	0	9
EGFR/EGFR/EGF/EGF	-0.011	0.008	0	196	-10000	0	196
ARRB2	-0.005	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.004	0.032	2	-0.027	2	4
ARRB1	-0.014	0	-10000	0	-10000	0	0
FBXO8	0	0	-10000	0	-10000	0	0
TSHR	-0.014	0.001	0	4	-10000	0	4
EGF	-0.014	0.001	0	2	-10000	0	2
somatostatin receptor activity	0	0	0	1	-10000	0	1
ARAP2	0	0	0	1	-10000	0	1
mol:GDP	0.004	0.012	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	0	1	-10000	0	1
ITGA2B	-0.014	0	-10000	0	-10000	0	0
ARF6	-0.014	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.022	0.006	0	38	-10000	0	38
ADAP1	0	0	-10000	0	-10000	0	0
KIF13B	-0.014	0.001	0	2	-10000	0	2
HGF/MET	-0.017	0.003	0	12	-10000	0	12
PXN	-0.014	0	-10000	0	-10000	0	0
ARF6/GTP	0.005	0.018	0.072	1	-10000	0	1
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.012	0.01	0	203	-10000	0	203
ADRB2	-0.014	0.001	0	1	-10000	0	1
receptor agonist activity	0	0	0	1	-10000	0	1
actin filament binding	0	0	0	1	-10000	0	1
SRC	-0.014	0	-10000	0	-10000	0	0
ITGB3	-0.014	0	-10000	0	-10000	0	0
GNAQ	-0.014	0	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0	0	2	-10000	0	2
ARF6/GDP	0	0.016	0.095	8	-10000	0	8
ARF6/GDP/GULP/ACAP1	0.002	0.018	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.024	0	-10000	0	-10000	0	0
ACAP1	0	0	-10000	0	-10000	0	0
ACAP2	0	0	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	-0.008	0	-10000	0	-10000	0	0
EFNA1	-0.014	0.003	0	24	-10000	0	24
HGF	-0.014	0.001	0	2	-10000	0	2
CYTH3	0	0	0	1	-10000	0	1
CYTH2	0	0	-10000	0	-10000	0	0
NCK1	-0.014	0.002	0	11	-10000	0	11
fibronectin binding	0	0	0	1	-10000	0	1
endosomal lumen acidification	0	0	0	1	-10000	0	1
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	-0.014	0.001	0	4	-10000	0	4
GNAQ/ARNO	0	0.006	-10000	0	-10000	0	0
mol:Phosphatidic acid	0	0	-10000	0	-10000	0	0
PIP3-E	-0.001	0.003	0	502	-10000	0	502
MET	-0.014	0.002	0	10	-10000	0	10
GNA14	-0.014	0.001	0	2	-10000	0	2
GNA15	-0.014	0.002	0	7	-10000	0	7
GIT1	-0.014	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0	1	-10000	0	1
GNA11	-0.014	0	-10000	0	-10000	0	0
LHCGR	-0.014	0	-10000	0	-10000	0	0
AGTR1	-0.014	0.001	0	2	-10000	0	2
desensitization of G-protein coupled receptor protein signaling pathway	-0.008	0	-10000	0	-10000	0	0
IPCEF1/ARNO	-0.001	0.003	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.017	0	-10000	0	-10000	0	0

×

TRAIL 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.Total.Perturbations
TNFSF10	-0.013	0.004	0	46	-9999	46
positive regulation of NF-kappaB transcription factor activity	-0.016	0.005	0	46	-9999	46
MAP2K4	-0.004	0.017	-10000	0	-9999	0
IKBKB	-0.014	0	-10000	0	-9999	0
TNFRSF10B	-0.014	0.002	0	8	-9999	8
TNFRSF10A	0	0	-10000	0	-9999	0
SMPD1	-0.007	0.002	0	52	-9999	52
IKBKG	-0.014	0	-10000	0	-9999	0
mol:GTP	0	0	-10000	0	-9999	0
TNFRSF10D	-0.014	0	-10000	0	-9999	0
TRAIL/TRAILR2	-0.015	0.005	0	52	-9999	52
TRAIL/TRAILR3	-0.016	0.005	0	46	-9999	46
TRAIL/TRAILR1	-0.008	0.002	0	46	-9999	46
TRAIL/TRAILR4	-0.016	0.005	0	46	-9999	46
TRAIL/TRAILR1/DAP3/GTP	-0.011	0.003	0	46	-9999	46
IKK complex	-0.013	0.006	-10000	0	-9999	0
RIPK1	-0.014	0.002	0	9	-9999	9
response to oxidative stress	0	0	-10000	0	-9999	0
DAP3/GTP	-0.009	0	-10000	0	-9999	0
MAPK3	-0.016	0.005	0	46	-9999	46
MAP3K1	-0.004	0.005	0.058	1	-9999	1
TRAILR4 (trimer)	-0.014	0	-10000	0	-9999	0
TRADD	-0.014	0	-10000	0	-9999	0
TRAILR1 (trimer)	0	0	-10000	0	-9999	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.008	0.003	-10000	0	-9999	0
CFLAR	-0.014	0.001	0	5	-9999	5
MAPK1	-0.015	0.005	0	58	-9999	58
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.02	0.007	0	54	-9999	54
mol:ceramide	-0.007	0.002	0	52	-9999	52
FADD	-0.014	0.001	0	2	-9999	2
MAPK8	-0.008	0.018	0.09	4	-9999	4
TRAF2	-0.014	0	-10000	0	-9999	0
TRAILR3 (trimer)	-0.014	0	-10000	0	-9999	0
CHUK	-0.014	0.001	0	1	-9999	1
TRAIL/TRAILR1/FADD	-0.012	0.004	0	47	-9999	47
DAP3	-0.014	0	-10000	0	-9999	0
CASP10	-0.003	0.03	0.087	51	-9999	51
JNK cascade	-0.016	0.005	0	46	-9999	46
TRAIL (trimer)	-0.013	0.004	0	46	-9999	46
TNFRSF10C	-0.014	0	-10000	0	-9999	0
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.015	0.005	0	47	-9999	47
TRAIL/TRAILR2/FADD	-0.018	0.006	0	53	-9999	53
cell death	-0.007	0.002	0	52	-9999	52
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.01	0.004	-10000	0	-9999	0
TRAILR2 (trimer)	-0.014	0.002	0	8	-9999	8
CASP8	0.002	0.013	-10000	0	-9999	0
negative regulation of caspase activity	0	0	-10000	0	-9999	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.024	0.009	-10000	0	-9999	0

×

Caspase cascade in apoptosis

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
TOP1	0.001	0.025	0.12	3	-10000	0	3
ACTA1	-0.009	0.03	0.1	10	-0.097	20	30
NUMA1	0.001	0.025	0.13	2	-10000	0	2
SPTAN1	-0.009	0.031	0.12	11	-0.098	15	26
LIMK1	-0.012	0.029	0.11	5	-0.099	18	23
BIRC3	-0.013	0.003	0	33	-10000	0	33
BIRC2	-0.014	0	-10000	0	-10000	0	0
BAX	-0.014	0.002	0	7	-10000	0	7
CASP10	-0.019	0.004	0	22	-10000	0	22
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0	0.029	0.12	3	-0.24	2	5
DIABLO	-0.014	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.009	0.031	0.12	11	-0.097	15	26
response to UV	0	0	-10000	0	-10000	0	0
CRADD	-0.014	0	-10000	0	-10000	0	0
GSN	-0.009	0.033	0.11	13	-0.098	20	33
MADD	-0.014	0.001	0	4	-10000	0	4
TFAP2A	0.01	0.008	-10000	0	-10000	0	0
BID	-0.009	0.002	0	36	-10000	0	36
MAP3K1	0	0.014	-10000	0	-10000	0	0
TRADD	-0.014	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	-0.017	0.001	0	4	-10000	0	4
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.002	0.042	0.13	30	-0.094	17	47
CASP9	-0.014	0.001	0	4	-10000	0	4
DNA repair	0.001	0.022	0.086	4	-10000	0	4
neuron apoptosis	0.005	0.028	-10000	0	-0.58	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.006	0.028	0.12	3	-10000	0	3
APAF1	-0.014	0	-10000	0	-10000	0	0
CASP6	0.006	0.019	-10000	0	-10000	0	0
TRAF2	-0.014	0	-10000	0	-10000	0	0
ICAD/CAD	-0.016	0.028	0.1	5	-0.1	15	20
CASP7	0.002	0.039	-10000	0	-0.13	30	30
KRT18	0.008	0.012	-10000	0	-10000	0	0
apoptosis	-0.008	0.035	0.13	3	-10000	0	3
DFFA	-0.012	0.029	0.11	5	-0.096	22	27
DFFB	-0.012	0.029	0.11	5	-0.099	18	23
PARP1	-0.001	0.022	-10000	0	-0.087	4	4
actin filament polymerization	0.011	0.027	0.093	18	-0.11	5	23
TNF	-0.014	0.001	0	2	-10000	0	2
CYCS	-0.004	0.019	0.08	14	-0.18	1	15
SATB1	0.001	0.019	-10000	0	-10000	0	0
SLK	-0.012	0.029	0.11	5	-0.099	18	23
p15 BID/BAX	-0.009	0.02	0.064	35	-10000	0	35
CASP2	0.006	0.026	0.078	23	-10000	0	23
JNK cascade	0	0.014	-10000	0	-10000	0	0
CASP3	-0.007	0.031	0.11	8	-0.097	22	30
LMNB2	0.011	0.021	-10000	0	-10000	0	0
RIPK1	-0.014	0.002	0	9	-10000	0	9
CASP4	-0.011	0.006	0	107	-10000	0	107
Mammalian IAPs/DIABLO	-0.017	0.004	0	33	-10000	0	33
negative regulation of DNA binding	0.01	0.008	-10000	0	-10000	0	0
stress fiber formation	-0.012	0.029	0.11	5	-0.098	18	23
GZMB	-0.016	0.003	0	22	-10000	0	22
CASP1	-0.003	0.003	0	195	-10000	0	195
LMNB1	0.013	0.021	-10000	0	-10000	0	0
APP	0.005	0.028	-10000	0	-0.59	1	1
TNFRSF1A	-0.009	0.007	0	183	-10000	0	183
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.008	0.001	0	10	-10000	0	10
VIM	-0.003	0.036	0.13	4	-10000	0	4
LMNA	0.01	0.02	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.012	0.028	0.087	22	-10000	0	22
LRDD	-0.014	0	-10000	0	-10000	0	0
SREBF1	-0.012	0.029	0.11	5	-0.099	18	23
APAF-1/Caspase 9	0.011	0.008	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.001	0.025	0.13	2	-10000	0	2
CFL2	-0.011	0.028	0.11	5	-0.094	18	23
GAS2	-0.003	0.042	0.11	38	-0.097	20	58
positive regulation of apoptosis	0.014	0.021	-10000	0	-10000	0	0
PRF1	-0.014	0.002	0	12	-10000	0	12

×

Syndecan-2-mediated signaling events

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.Total.Perturbations
Syndecan-2/Fibronectin	-0.011	0.01	0.097	3	-9999	3
EPHB2	-0.014	0.001	0	2	-9999	2
Syndecan-2/TACI	-0.014	0.011	0.097	5	-9999	5
LAMA1	0	0	-10000	0	-9999	0
Syndecan-2/alpha2 ITGB1	-0.017	0.017	0.09	9	-9999	9
HRAS	-0.014	0.001	0	2	-9999	2
Syndecan-2/CASK	-0.008	0.002	-10000	0	-9999	0
ITGA5	-0.012	0.005	0	74	-9999	74
BAX	-0.015	0.014	-10000	0	-9999	0
EPB41	-0.014	0	-10000	0	-9999	0
positive regulation of cell-cell adhesion	-0.013	0.002	-10000	0	-9999	0
LAMA3	-0.014	0.002	0	15	-9999	15
EZR	0	0	-10000	0	-9999	0
mol:PI-4-5-P2	0	0	-10000	0	-9999	0
CAV2	-0.012	0.005	0	72	-9999	72
Syndecan-2/MMP2	-0.007	0.01	0.097	2	-9999	2
RP11-540L11.1	0	0	-10000	0	-9999	0
alpha2 ITGB1	-0.014	0.007	0	93	-9999	93
dendrite morphogenesis	-0.014	0.011	0.097	5	-9999	5
Syndecan-2/GM-CSF	-0.014	0.011	0.097	5	-9999	5
determination of left/right symmetry	-0.009	0.013	0.13	5	-9999	5
Syndecan-2/PKC delta	-0.014	0.011	0.097	5	-9999	5
GNB2L1	-0.014	0	-10000	0	-9999	0
MAPK3	-0.016	0.019	0.1	13	-9999	13
MAPK1	-0.016	0.019	0.1	13	-9999	13
Syndecan-2/RACK1	-0.016	0.011	0.089	5	-9999	5
NF1	-0.014	0	-10000	0	-9999	0
FGFR/FGF/Syndecan-2	-0.009	0.013	0.13	5	-9999	5
ITGA2	-0.012	0.005	0	93	-9999	93
MAPK8	-0.015	0.021	0.2	5	-9999	5
Syndecan-2/alpha2/beta1 Integrin	-0.013	0.012	0.089	5	-9999	5
Syndecan-2/Kininogen	-0.014	0.011	0.097	5	-9999	5
ITGB1	-0.014	0	-10000	0	-9999	0
SRC	-0.019	0.018	0.09	14	-9999	14
Syndecan-2/CASK/Protein 4.1	-0.013	0.002	-10000	0	-9999	0
extracellular matrix organization	-0.013	0.011	0.097	5	-9999	5
actin cytoskeleton reorganization	-0.011	0.01	0.097	3	-9999	3
Syndecan-2/Caveolin-2/Ras	-0.015	0.012	0.094	4	-9999	4
Syndecan-2/Laminin alpha3	-0.014	0.01	0.097	4	-9999	4
Syndecan-2/RasGAP	-0.02	0.011	0.087	5	-9999	5
alpha5/beta1 Integrin	-0.015	0.006	0	74	-9999	74
PRKCD	-0.014	0	-10000	0	-9999	0
Syndecan-2 dimer	-0.014	0.011	0.097	5	-9999	5
GO:0007205	-0.001	0	-10000	0	-9999	0
DNA mediated transformation	0	0	-10000	0	-9999	0
Syndecan-2/RasGAP/Src	-0.024	0.012	0.081	6	-9999	6
RHOA	-0.014	0.001	0	2	-9999	2
SDCBP	-0.014	0	-10000	0	-9999	0
TNFRSF13B	-0.014	0	-10000	0	-9999	0
RASA1	-0.014	0.002	0	8	-9999	8
alpha2/beta1 Integrin	-0.014	0.007	0	93	-9999	93
Syndecan-2/Synbindin	-0.014	0.011	0.097	5	-9999	5
TGFB1	-0.013	0.003	0	27	-9999	27
CASP3	-0.013	0.018	0.1	10	-9999	10
FN1	-0.011	0.006	0	104	-9999	104
Syndecan-2/IL8	-0.011	0.012	0.097	5	-9999	5
SDC2	-0.009	0.013	0.13	5	-9999	5
KNG1	-0.014	0.001	0	1	-9999	1
Syndecan-2/Neurofibromin	-0.014	0.011	0.097	5	-9999	5
TRAPPC4	-0.014	0.001	0	1	-9999	1
CSF2	-0.014	0	-10000	0	-9999	0
Syndecan-2/TGFB1	-0.013	0.012	0.097	5	-9999	5
Syndecan-2/Syntenin/PI-4-5-P2	-0.013	0.002	-10000	0	-9999	0
Syndecan-2/Ezrin	-0.013	0.003	-10000	0	-9999	0
PRKACA	-0.016	0.019	0.1	13	-9999	13
angiogenesis	-0.011	0.012	0.097	5	-9999	5
MMP2	-0.007	0.007	0	250	-9999	250
IL8	-0.011	0.006	0	115	-9999	115
calcineurin-NFAT signaling pathway	-0.014	0.011	0.097	5	-9999	5

×

TCGA08_p53

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
CDKN2A	-0.008	0.003	0	59	-10000	0	59
TP53	0.002	0.015	-10000	0	-0.097	12	12
Senescence	0.002	0.015	-10000	0	-0.097	12	12
Apoptosis	0.002	0.015	-10000	0	-0.097	12	12
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	-0.003	0.025	0.16	12	-10000	0	12
MDM4	-0.014	0.002	0	13	-10000	0	13

×

Paxillin-dependent events mediated by a4b1

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
CRKL	-0.014	0	-9999	0	-10000	0	0
Rac1/GDP	-0.014	0	-9999	0	-10000	0	0
DOCK1	-0.014	0	-9999	0	-10000	0	0
ITGA4	-0.014	0.001	0	5	-10000	0	5
RAC1	-0.014	0	-9999	0	-10000	0	0
alpha4/beta7 Integrin	-0.017	0.002	0	5	-10000	0	5
mol:GTP	0	0	-9999	0	-10000	0	0
CRK	-0.014	0	-9999	0	-10000	0	0
alpha4/beta1 Integrin	-0.02	0.002	0	5	-10000	0	5
alpha4/beta7 Integrin/Paxillin	-0.023	0.002	0	5	-10000	0	5
lamellipodium assembly	-0.021	0.048	-9999	0	-0.19	36	36
PIK3CA	-0.014	0.003	0	25	-10000	0	25
PI3K	-0.015	0.005	0	60	-10000	0	60
ARF6	-0.014	0	-9999	0	-10000	0	0
TLN1	-0.013	0.004	0	46	-10000	0	46
PXN	-0.017	0	-9999	0	-10000	0	0
PIK3R1	-0.013	0.004	0	36	-10000	0	36
ARF6/GTP	-0.029	0.003	-9999	0	-10000	0	0
cell adhesion	-0.025	0.008	-9999	0	-10000	0	0
CRKL/CBL	-0.017	0	-9999	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.023	0.002	0	5	-10000	0	5
ITGB1	-0.014	0	-9999	0	-10000	0	0
ITGB7	-0.014	0.001	0	2	-10000	0	2
ARF6/GDP	-0.014	0	-9999	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.009	0.013	-9999	0	-10000	0	0
p130Cas/Crk/Dock1	-0.014	0	-9999	0	-10000	0	0
VCAM1	-0.005	0.007	0	351	-10000	0	351
alpha4/beta1 Integrin/Paxillin/Talin	-0.025	0.008	-9999	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.027	0.003	-9999	0	-10000	0	0
BCAR1	0	0	-9999	0	-10000	0	0
mol:GDP	0.027	0.003	-9999	0	-10000	0	0
CBL	-0.014	0	-9999	0	-10000	0	0
PRKACA	-0.014	0	-9999	0	-10000	0	0
GIT1	-0.014	0	-9999	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.025	0.008	-9999	0	-10000	0	0
Rac1/GTP	-0.023	0.052	-9999	0	-0.21	36	36

×

IL2 signaling events mediated by STAT5

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
GAB2	-0.014	0.002	0.022	1	-10000	0	1
ELF1	-0.02	0.004	0.001	14	-10000	0	14
CCNA2	-0.01	0.006	0	139	-10000	0	139
PIK3CA	-0.014	0.003	0.001	26	-10000	0	26
JAK3	-0.014	0.002	0.021	1	-10000	0	1
PIK3R1	-0.013	0.004	0.001	37	-10000	0	37
JAK1	-0.014	0.002	0.004	6	-10000	0	6
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.012	0.031	0.22	1	-0.21	2	3
SHC1	-0.013	0.004	0	47	-10000	0	47
SP1	-0.019	0.004	0	27	-10000	0	27
IL2RA	-0.017	0.003	0.001	14	-10000	0	14
IL2RB	-0.014	0.002	0.004	5	-10000	0	5
SOS1	0	0.001	0.013	1	-10000	0	1
IL2RG	-0.014	0.002	0.022	1	-10000	0	1
G1/S transition of mitotic cell cycle	0.008	0.067	0.18	14	-0.31	13	27
PTPN11	-0.014	0.002	0.022	1	-10000	0	1
CCND2	-0.017	0.004	0	27	-10000	0	27
LCK	-0.014	0.002	0.004	5	-10000	0	5
GRB2	-0.014	0.002	0.004	6	-10000	0	6
IL2	-0.014	0.002	0.022	1	-10000	0	1
CDK6	-0.014	0	-10000	0	-10000	0	0
CCND3	-0.012	0.032	0.3	1	-10000	0	1

×

Signaling events mediated by PRL

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
CCNE1	-0.014	0.002	0	7	-10000	0	7
mol:Halofuginone	-0.003	0	-10000	0	-10000	0	0
ITGA1	0	0	-10000	0	-10000	0	0
CDKN1A	-0.003	0.016	-10000	0	-0.31	1	1
PRL-3/alpha Tubulin	-0.016	0.004	0	31	-10000	0	31
mol:Ca2+	-0.012	0.005	0	74	-10000	0	74
AGT	-0.013	0.004	0	44	-10000	0	44
CCNA2	0.008	0.049	0.09	140	-10000	0	140
TUBA1B	-0.014	0	-10000	0	-10000	0	0
EGR1	-0.012	0.008	0.17	1	-10000	0	1
CDK2/Cyclin E1	-0.005	0.025	0.13	3	-0.28	1	4
MAPK3	-0.016	0.004	0	31	-10000	0	31
PRL-2 /Rab GGTase beta	-0.017	0.001	0	1	-10000	0	1
MAPK1	-0.016	0.005	0	48	-10000	0	48
PTP4A1	-0.017	0.003	0	21	-10000	0	21
PTP4A3	-0.013	0.003	0	31	-10000	0	31
PTP4A2	-0.014	0.001	0	1	-10000	0	1
ITGB1	-0.016	0.004	0	31	-10000	0	31
SRC	-0.014	0	-10000	0	-10000	0	0
RAC1	-0.002	0.009	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	-0.017	0	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.018	0.021	0.21	1	-10000	0	1
RABGGTA	-0.014	0	-10000	0	-10000	0	0
BCAR1	-0.005	0.001	0	31	-10000	0	31
RHOC	-0.001	0.009	-10000	0	-10000	0	0
RHOA	-0.003	0.021	-10000	0	-0.31	2	2
cell motility	0.011	0.026	0.16	5	-10000	0	5
PRL-1/alpha Tubulin	-0.018	0.021	0.21	1	-10000	0	1
PRL-3/alpha1 Integrin	-0.008	0.002	0	31	-10000	0	31
ROCK1	0.01	0.023	0.14	2	-10000	0	2
RABGGTB	-0.014	0	-10000	0	-10000	0	0
CDK2	-0.013	0.003	0	27	-10000	0	27
mitosis	-0.014	0.02	0.1	15	-10000	0	15
ATF5	-0.014	0.001	0	1	-10000	0	1

×

BMP receptor 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
BMP7/BMPR2/BMPR1A-1B/FS	-0.026	0.006	-10000	0	-10000	0	0
SMAD6-7/SMURF1	-0.02	0.001	0	1	-10000	0	1
NOG	0	0	-10000	0	-10000	0	0
SMAD9	0.006	0.008	-10000	0	-10000	0	0
SMAD4	-0.011	0.006	0	126	-10000	0	126
SMAD5	-0.004	0.016	0.086	8	-10000	0	8
BMP7/USAG1	-0.017	0.002	0	9	-10000	0	9
SMAD5/SKI	-0.008	0.018	0.092	6	-10000	0	6
SMAD1	0	0.04	0.13	5	-0.15	16	21
BMP2	-0.013	0.004	0	54	-10000	0	54
SMAD1/SMAD1/SMAD4	-0.019	0.032	-10000	0	-0.15	14	14
BMPR1A	-0.014	0.002	0	6	-10000	0	6
BMPR1B	-0.014	0.001	0	1	-10000	0	1
BMPR1A-1B/BAMBI	-0.019	0.005	0	41	-10000	0	41
AHSG	-0.014	0.001	0	2	-10000	0	2
CER1	-0.014	0	-10000	0	-10000	0	0
BMP2-4/CER1	-0.018	0.007	0	62	-10000	0	62
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.004	0.016	-10000	0	-10000	0	0
BMP2-4 (homodimer)	-0.015	0.005	0	62	-10000	0	62
RGMB	0	0	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.023	0.003	0	9	-10000	0	9
RGMA	0	0	-10000	0	-10000	0	0
SMURF1	-0.014	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	0	0.014	0.043	53	-10000	0	53
BMP2-4/USAG1	-0.018	0.007	0	66	-10000	0	66
SMAD6/SMURF1/SMAD5	-0.008	0.018	0.092	6	-10000	0	6
SOSTDC1	-0.014	0.002	0	7	-10000	0	7
BMP7/BMPR2/BMPR1A-1B	-0.023	0.003	0	9	-10000	0	9
SKI	-0.014	0	-10000	0	-10000	0	0
BMP6 (homodimer)	-0.014	0.001	0	2	-10000	0	2
HFE2	0	0	-10000	0	-10000	0	0
ZFYVE16	-0.014	0.001	0	5	-10000	0	5
MAP3K7	-0.014	0.001	0	1	-10000	0	1
BMP2-4/CHRD	-0.018	0.007	0	62	-10000	0	62
SMAD5/SMAD5/SMAD4	-0.007	0.013	0.084	2	-10000	0	2
MAPK1	-0.014	0.003	0	17	-10000	0	17
TAK1/TAB family	-0.014	0.024	0.05	64	-10000	0	64
BMP7 (homodimer)	-0.014	0.001	0	2	-10000	0	2
NUP214	-0.014	0	-10000	0	-10000	0	0
BMP6/FETUA	-0.017	0.001	0	4	-10000	0	4
SMAD1/SKI	-0.003	0.041	0.13	5	-0.15	16	21
SMAD6	-0.014	0	-10000	0	-10000	0	0
CTDSP2	-0.013	0.004	0	37	-10000	0	37
BMP2-4/FETUA	-0.018	0.007	0	63	-10000	0	63
MAP3K7IP1	-0.014	0	-10000	0	-10000	0	0
GREM1	-0.014	0.003	0	23	-10000	0	23
BMPR2 (homodimer)	-0.014	0	-10000	0	-10000	0	0
GADD34/PP1CA	-0.02	0.002	0	6	-10000	0	6
BMPR1A-1B (homodimer)	-0.017	0.002	0	7	-10000	0	7
CHRDL1	0	0	-10000	0	-10000	0	0
ENDOFIN/SMAD1	-0.003	0.041	0.13	5	-0.15	16	21
SMAD6-7/SMURF1/SMAD1	-0.009	0.044	0.12	5	-0.15	16	21
SMAD6/SMURF1	-0.014	0	-10000	0	-10000	0	0
BAMBI	-0.013	0.004	0	36	-10000	0	36
SMURF2	-0.014	0.001	0	2	-10000	0	2
BMP2-4/CHRDL1	-0.012	0.004	0	62	-10000	0	62
BMP2-4/GREM1	-0.017	0.007	0	82	-10000	0	82
SMAD7	-0.014	0.001	0	1	-10000	0	1
SMAD8A/SMAD8A/SMAD4	0.008	0.007	-10000	0	-10000	0	0
SMAD1/SMAD6	-0.003	0.041	0.13	5	-0.15	16	21
TAK1/SMAD6	-0.017	0.001	0	1	-10000	0	1
BMP7	-0.014	0.001	0	2	-10000	0	2
BMP6	-0.014	0.001	0	2	-10000	0	2
MAP3K7IP2	-0.014	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	0	0.015	0.043	60	-10000	0	60
PPM1A	-0.014	0	-10000	0	-10000	0	0
SMAD1/SMURF2	-0.003	0.041	0.13	5	-0.15	16	21
SMAD7/SMURF1	-0.017	0.001	0	1	-10000	0	1
CTDSPL	-0.014	0	-10000	0	-10000	0	0
PPP1CA	-0.014	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
CTDSP1	-0.014	0.001	0	3	-10000	0	3
PPP1R15A	-0.014	0.001	0	1	-10000	0	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.001	0.014	0.043	49	-10000	0	49
CHRD	-0.014	0	-10000	0	-10000	0	0
BMPR2	-0.014	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.005	0.002	-10000	0	-10000	0	0
BMP4	-0.014	0.002	0	8	-10000	0	8
FST	-0.014	0.002	0	16	-10000	0	16
BMP2-4/NOG	-0.012	0.004	0	62	-10000	0	62
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.027	0.004	-10000	0	-10000	0	0

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.006	0.027	0.23	3	-0.14	5	8
SMARCC2	-0.014	0.001	0	1	-10000	0	1
SMARCC1	-0.014	0.003	0	18	-10000	0	18
TBX21	-0.002	0.023	0.14	4	-10000	0	4
SUMO2	-0.014	0.005	0.021	10	-10000	0	10
STAT1 (dimer)	-0.003	0.039	0.11	58	-10000	0	58
FKBP4	-0.014	0	-10000	0	-10000	0	0
FKBP5	-0.014	0.003	0	26	-10000	0	26
GR alpha/HSP90/FKBP51/HSP90	-0.009	0.023	-10000	0	-0.13	2	2
PRL	-0.052	0.069	0.3	3	-10000	0	3
cortisol/GR alpha (dimer)/TIF2	0.007	0.05	-10000	0	-0.29	3	3
RELA	0.007	0.057	0.096	137	-10000	0	137
FGG	0.093	0.14	0.31	26	-0.29	3	29
GR beta/TIF2	-0.01	0.024	-10000	0	-0.14	3	3
IFNG	-0.081	0.11	0.34	4	-0.29	3	7
apoptosis	-0.016	0.087	-10000	0	-0.4	4	4
CREB1	-0.016	0.015	0.11	7	-10000	0	7
histone acetylation	0.003	0.016	-10000	0	-10000	0	0
BGLAP	0.001	0.02	0.15	1	-10000	0	1
GR/PKAc	0.032	0.06	0.13	22	-10000	0	22
NF kappa B1 p50/RelA	0.004	0.071	0.14	103	-10000	0	103
SMARCD1	-0.014	0	-10000	0	-10000	0	0
MDM2	0.037	0.054	0.13	23	-0.1	2	25
GATA3	-0.017	0.002	-10000	0	-10000	0	0
AKT1	-0.016	0.015	-10000	0	-0.12	10	10
CSF2	-0.067	0.074	-10000	0	-10000	0	0
GSK3B	-0.014	0.006	0.021	10	-10000	0	10
NR1I3	-0.011	0.087	-10000	0	-0.4	2	2
CSN2	0.1	0.14	0.29	28	-0.26	3	31
BRG1/BAF155/BAF170/BAF60A	-0.023	0.005	0	21	-10000	0	21
NFATC1	-0.018	0	-10000	0	-10000	0	0
POU2F1	-0.014	0.013	0.11	6	-10000	0	6
CDKN1A	0.042	0.1	0.33	51	-10000	0	51
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.001	0.003	0.016	1	-0.014	1	2
SFN	-0.013	0.003	0	33	-10000	0	33
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.033	0.06	0.13	18	-10000	0	18
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.011	0.093	0.38	4	-0.48	4	8
JUN	-0.004	0.055	0.36	9	-10000	0	9
IL4	0	0.019	0.15	1	-10000	0	1
CDK5R1	-0.011	0.007	0.015	9	-10000	0	9
PRKACA	-0.014	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.022	0.04	-10000	0	-10000	0	0
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.032	0.062	0.13	16	-0.13	1	17
cortisol/GR alpha (monomer)	0.006	0.054	-10000	0	-0.34	3	3
NCOA2	-0.014	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.011	0.029	0.16	10	-10000	0	10
AP-1/NFAT1-c-4	-0.036	0.071	0.43	8	-10000	0	8
AFP	-0.073	0.068	0.5	1	-10000	0	1
SUV420H1	-0.014	0.001	0	2	-10000	0	2
IRF1	-0.005	0.042	0.28	8	-0.18	3	11
TP53	-0.001	0.048	0.26	4	-10000	0	4
PPP5C	-0.014	0	-10000	0	-10000	0	0
KRT17	-0.079	0.11	0.49	4	-0.29	3	7
KRT14	0.006	0.04	0.36	6	-10000	0	6
TBP	-0.018	0.001	-10000	0	-10000	0	0
CREBBP	-0.014	0.013	-10000	0	-0.12	8	8
HDAC1	-0.011	0.004	-10000	0	-10000	0	0
HDAC2	-0.014	0.001	-10000	0	-10000	0	0
AP-1	-0.036	0.071	0.43	8	-10000	0	8
MAPK14	-0.014	0.005	0.02	10	-10000	0	10
MAPK10	-0.008	0.008	0.022	8	-10000	0	8
MAPK11	-0.014	0.005	0.021	10	-10000	0	10
KRT5	-0.08	0.11	0.45	4	-0.3	2	6
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
NCOA1	-0.015	0.009	0.052	9	-10000	0	9
STAT1	-0.003	0.039	0.11	58	-10000	0	58
CGA	0.001	0.022	0.21	2	-10000	0	2
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.054	0.072	0.25	1	-0.2	1	2
MAPK3	-0.014	0.006	0.022	10	-10000	0	10
MAPK1	-0.014	0.006	0.02	9	-10000	0	9
ICAM1	-0.062	0.087	0.21	5	-0.2	25	30
NFKB1	0.006	0.055	0.095	136	-10000	0	136
MAPK8	-0.003	0.042	0.27	8	-10000	0	8
MAPK9	-0.014	0.005	0.02	10	-10000	0	10
cortisol/GR alpha (dimer)	-0.019	0.088	-10000	0	-0.38	6	6
BAX	0.023	0.064	0.39	7	-10000	0	7
POMC	-0.087	0.08	-10000	0	-10000	0	0
EP300	-0.014	0.013	-10000	0	-0.12	8	8
cortisol/GR alpha (dimer)/p53	0.008	0.052	0.32	1	-0.29	3	4
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.032	0.11	13	-0.086	2	15
SGK1	0.024	0.029	-10000	0	-0.15	6	6
IL13	-0.066	0.086	0.29	3	-10000	0	3
IL6	-0.06	0.095	0.32	8	-0.2	25	33
PRKACG	-0.014	0	-10000	0	-10000	0	0
IL5	-0.068	0.084	-10000	0	-10000	0	0
IL2	-0.081	0.11	0.34	4	-0.3	2	6
CDK5	-0.013	0.005	0.015	9	-10000	0	9
PRKACB	-0.013	0.004	0	46	-10000	0	46
HSP90AA1	-0.014	0	-10000	0	-10000	0	0
IL8	-0.054	0.11	0.29	27	-0.2	25	52
CDK5R1/CDK5	-0.013	0.01	0.028	9	-10000	0	9
NF kappa B1 p50/RelA/PKAc	0.005	0.076	0.14	112	-10000	0	112
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.008	0.049	-10000	0	-0.27	3	3
SMARCA4	-0.014	0.001	0	2	-10000	0	2
chromatin remodeling	0.055	0.084	0.19	26	-0.19	3	29
NF kappa B1 p50/RelA/Cbp	0.012	0.084	0.18	59	-10000	0	59
JUN (dimer)	-0.004	0.055	0.36	9	-10000	0	9
YWHAH	-0.007	0.007	0	284	-10000	0	284
VIPR1	-0.002	0.023	0.14	4	-10000	0	4
NR3C1	-0.003	0.053	0.18	20	-0.2	3	23
NR4A1	-0.016	0	-10000	0	-10000	0	0
TIF2/SUV420H1	-0.017	0.001	0	2	-10000	0	2
MAPKKK cascade	-0.016	0.087	-10000	0	-0.4	4	4
cortisol/GR alpha (dimer)/Src-1	0.007	0.049	-10000	0	-0.32	2	2
PBX1	-0.014	0.013	0.11	6	-10000	0	6
POU1F1	-0.014	0.013	0.11	6	-10000	0	6
SELE	-0.062	0.087	0.21	5	-0.2	25	30
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.055	0.085	0.19	26	-0.19	3	29
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.008	0.049	-10000	0	-0.27	3	3
mol:cortisol	-0.008	0.026	-10000	0	-0.19	3	3
MMP1	0.005	0.05	0.32	12	-10000	0	12

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.005	0.031	0.097	22	-10000	0	22
FYN	0.001	0.045	0.18	19	-10000	0	19
LAT/GRAP2/SLP76	-0.014	0.027	0.13	9	-10000	0	9
IKBKB	-0.014	0	-10000	0	-10000	0	0
AKT1	-0.006	0.037	0.15	18	-10000	0	18
B2M	-0.013	0.007	0.028	15	-10000	0	15
IKBKG	-0.01	0.014	0.043	16	-10000	0	16
MAP3K8	-0.013	0.004	0	42	-10000	0	42
mol:Ca2+	-0.011	0.003	-10000	0	-10000	0	0
integrin-mediated signaling pathway	-0.007	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.005	0.043	0.18	18	-10000	0	18
TRPV6	-0.01	0.001	-10000	0	-10000	0	0
CD28	-0.014	0.004	0.013	12	-10000	0	12
SHC1	0.003	0.048	0.15	38	-10000	0	38
receptor internalization	-0.002	0.029	0.16	12	-10000	0	12
PRF1	0.001	0.053	0.34	12	-10000	0	12
KRAS	-0.014	0.002	0	9	-10000	0	9
GRB2	-0.014	0.001	0	5	-10000	0	5
COT/AKT1	-0.011	0.024	0.12	9	-10000	0	9
LAT	-0.005	0.037	0.18	14	-10000	0	14
EntrezGene:6955	0	0.003	0.023	12	-10000	0	12
CD3D	-0.013	0.006	0.029	9	-10000	0	9
CD3E	-0.013	0.008	0.028	17	-10000	0	17
CD3G	-0.014	0.007	0.031	11	-10000	0	11
RASGRP2	-0.002	0.006	0.042	2	-10000	0	2
RASGRP1	-0.061	0.073	0.16	10	-0.15	184	194
HLA-A	-0.013	0.008	0.027	18	-10000	0	18
RASSF5	0	0	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	-0.007	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.017	0.029	0.08	16	-0.097	5	21
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.017	0.009	-10000	0	-10000	0	0
PRKCA	-0.017	0.023	0.07	21	-10000	0	21
GRAP2	-0.014	0	-10000	0	-10000	0	0
mol:IP3	-0.02	0.019	-10000	0	-10000	0	0
EntrezGene:6957	0	0.004	0.024	12	-10000	0	12
TCR/CD3/MHC I/CD8	-0.002	0.028	0.17	12	-10000	0	12
ORAI1	0.001	0	-10000	0	-10000	0	0
CSK	-0.004	0.036	0.17	14	-10000	0	14
B7 family/CD28	-0.006	0.051	0.29	12	-10000	0	12
CHUK	-0.014	0.001	0	1	-10000	0	1
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.001	0.037	0.17	16	-10000	0	16
PTPN6	-0.002	0.044	0.19	20	-10000	0	20
VAV1	-0.005	0.037	0.17	15	-10000	0	15
Monovalent TCR/CD3	-0.006	0.014	0.089	10	-10000	0	10
CBL	-0.014	0	-10000	0	-10000	0	0
LCK	0.003	0.046	0.18	22	-10000	0	22
PAG1	-0.001	0.036	0.18	14	-10000	0	14
RAP1A	-0.014	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.001	0.039	0.18	16	-10000	0	16
CD80	-0.014	0.004	0.012	13	-10000	0	13
CD86	-0.013	0.005	0.003	34	-10000	0	34
PDK1/CARD11/BCL10/MALT1	-0.016	0.01	-10000	0	-10000	0	0
HRAS	-0.014	0.001	0	2	-10000	0	2
GO:0035030	-0.01	0.04	0.23	12	-10000	0	12
CD8A	0	0.004	0.025	12	-10000	0	12
CD8B	-0.013	0.008	0.028	17	-10000	0	17
PTPRC	-0.011	0.006	0	128	-10000	0	128
PDK1/PKC theta	-0.012	0.042	0.18	14	-10000	0	14
CSK/PAG1	-0.005	0.035	0.17	14	-10000	0	14
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.015	0.012	0.038	24	-10000	0	24
GRAP2/SLP76	-0.009	0.032	0.16	10	-10000	0	10
STIM1	-0.01	0.002	-10000	0	-10000	0	0
RAS family/GTP	-0.011	0.037	0.11	17	-0.14	11	28
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.002	0.03	0.16	13	-10000	0	13
mol:DAG	-0.023	0.011	-10000	0	-10000	0	0
RAP1A/GDP	-0.01	0.014	0.036	15	-0.047	5	20
PLCG1	-0.014	0	-10000	0	-10000	0	0
CD247	-0.014	0.006	0.031	10	-10000	0	10
cytotoxic T cell degranulation	0.001	0.052	0.33	12	-10000	0	12
RAP1A/GTP	-0.003	0.002	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.004	0.041	0.17	18	-10000	0	18
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.023	0.024	-10000	0	-10000	0	0
NRAS	-0.011	0.006	0	136	-10000	0	136
ZAP70	-0.014	0	-10000	0	-10000	0	0
GRB2/SOS1	-0.008	0.001	0	5	-10000	0	5
LAT/GRAP2/SLP76/VAV1	-0.022	0.018	0.086	2	-10000	0	2
MALT1	-0.014	0.003	0	24	-10000	0	24
TRAF6	-0.014	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.007	0.01	0.053	12	-10000	0	12
CARD11	0	0	-10000	0	-10000	0	0
PRKCB	-0.018	0.009	-10000	0	-10000	0	0
PRKCE	-0.017	0.023	0.07	21	-10000	0	21
PRKCQ	-0.009	0.043	0.19	15	-10000	0	15
LCP2	-0.013	0.003	0	30	-10000	0	30
BCL10	-0.014	0.001	0	4	-10000	0	4
regulation of survival gene product expression	-0.005	0.035	0.15	18	-10000	0	18
IKK complex	-0.004	0.02	0.087	15	-10000	0	15
RAS family/GDP	-0.007	0.007	-10000	0	-0.018	108	108
MAP3K14	-0.011	0.03	0.14	14	-10000	0	14
PDPK1	-0.008	0.037	0.15	18	-10000	0	18
TCR/CD3/MHC I/CD8/Fyn	-0.004	0.019	0.13	8	-10000	0	8

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.013	0.001	0	2	-10000	0	2
cell-cell adhesion	0.033	0.01	-10000	0	-10000	0	0
Ephrin B/EPHB2/RasGAP	-0.025	0.007	-10000	0	-10000	0	0
ITSN1	-0.014	0	-10000	0	-10000	0	0
PIK3CA	-0.014	0.003	0	25	-10000	0	25
SHC1	-0.013	0.004	0	46	-10000	0	46
Ephrin B1/EPHB3	-0.013	0.002	0	13	-10000	0	13
Ephrin B1/EPHB1	-0.013	0.002	0	12	-10000	0	12
HRAS/GDP	-0.03	0.012	-10000	0	-0.093	13	13
Ephrin B/EPHB1/GRB7	-0.025	0.007	-10000	0	-10000	0	0
Endophilin/SYNJ1	-0.023	0.01	0.084	2	-10000	0	2
KRAS	-0.014	0.002	0	9	-10000	0	9
Ephrin B/EPHB1/Src	-0.025	0.007	-10000	0	-10000	0	0
endothelial cell migration	-0.019	0.007	0	71	-10000	0	71
GRB2	-0.014	0.001	0	5	-10000	0	5
GRB7	-0.014	0.001	0	1	-10000	0	1
PAK1	-0.029	0.009	0.08	2	-10000	0	2
HRAS	-0.014	0.001	0	2	-10000	0	2
RRAS	-0.023	0.01	0.084	2	-10000	0	2
DNM1	-0.003	0.005	0	432	-10000	0	432
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.022	0.017	0.084	11	-10000	0	11
lamellipodium assembly	-0.033	0.01	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.01	0.007	-10000	0	-0.072	5	5
PIK3R1	-0.013	0.004	0	36	-10000	0	36
EPHB2	-0.014	0.001	0	2	-10000	0	2
EPHB3	-0.014	0.002	0	13	-10000	0	13
EPHB1	-0.014	0.002	0	12	-10000	0	12
EPHB4	-0.014	0	-10000	0	-10000	0	0
mol:GDP	-0.02	0.018	0.07	11	-0.091	13	24
Ephrin B/EPHB2	-0.021	0.005	0	28	-10000	0	28
Ephrin B/EPHB3	-0.02	0.006	0	39	-10000	0	39
JNK cascade	-0.022	0.024	0.086	25	-10000	0	25
Ephrin B/EPHB1	-0.02	0.006	0	37	-10000	0	37
RAP1/GDP	-0.026	0.019	0.065	11	-0.088	13	24
EFNB2	-0.014	0.003	0	22	-10000	0	22
EFNB3	-0.014	0.001	0	4	-10000	0	4
EFNB1	-0.014	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.017	0.004	0	35	-10000	0	35
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	-0.014	0	-10000	0	-10000	0	0
CDC42/GTP	-0.031	0.015	0.063	11	-10000	0	11
Rap1/GTP	-0.034	0.01	-10000	0	-10000	0	0
axon guidance	-0.013	0.001	0	2	-10000	0	2
MAPK3	-0.013	0.019	-10000	0	-0.074	3	3
MAPK1	-0.012	0.019	-10000	0	-10000	0	0
Rac1/GDP	-0.026	0.02	0.07	11	-0.091	13	24
actin cytoskeleton reorganization	-0.029	0.019	-10000	0	-0.08	8	8
CDC42/GDP	-0.026	0.02	0.07	11	-0.091	13	24
PI3K	-0.019	0.007	0	71	-10000	0	71
EFNA5	-0.014	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.013	0.003	0	22	-10000	0	22
Ephrin B/EPHB2/Intersectin/N-WASP	-0.01	0.002	-10000	0	-10000	0	0
CDC42	-0.014	0	-10000	0	-10000	0	0
RAS family/GTP	-0.028	0.019	-10000	0	-10000	0	0
PTK2	-0.014	0.002	-10000	0	-10000	0	0
MAP4K4	-0.022	0.024	0.086	25	-10000	0	25
SRC	-0.014	0	-10000	0	-10000	0	0
KALRN	-0.014	0	-10000	0	-10000	0	0
Intersectin/N-WASP	-0.017	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.038	0.015	-10000	0	-10000	0	0
MAP2K1	-0.013	0.007	-10000	0	-0.072	3	3
WASL	-0.014	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.023	0.005	0	25	-10000	0	25
cell migration	-0.013	0.025	0.11	1	-0.11	2	3
NRAS	-0.011	0.006	0	136	-10000	0	136
SYNJ1	-0.023	0.01	0.084	2	-10000	0	2
PXN	-0.014	0	-10000	0	-10000	0	0
TF	-0.015	0.016	-10000	0	-10000	0	0
HRAS/GTP	-0.03	0.01	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2	-0.017	0.003	0	14	-10000	0	14
cell adhesion mediated by integrin	0.015	0.016	-10000	0	-10000	0	0
RAC1	-0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.026	0.017	0.072	13	-10000	0	13
RAC1-CDC42/GTP	-0.037	0.013	-10000	0	-10000	0	0
RASA1	-0.014	0.002	0	8	-10000	0	8
RAC1-CDC42/GDP	-0.03	0.02	0.069	11	-0.093	13	24
ruffle organization	-0.036	0.019	-10000	0	-10000	0	0
NCK1	-0.014	0.002	0	11	-10000	0	11
receptor internalization	-0.005	0.012	-10000	0	-10000	0	0
Ephrin B/EPHB2/KALRN	-0.026	0.006	-10000	0	-10000	0	0
ROCK1	-0.015	0.018	0.097	13	-10000	0	13
RAS family/GDP	-0.029	0.02	-10000	0	-0.086	8	8
Rac1/GTP	-0.035	0.011	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/Paxillin	-0.01	0.003	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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.Total.Perturbations
alphaV beta3 Integrin	-0.017	0.003	0	16	-9999	16
AKT1	0.014	0.059	0.2	29	-9999	29
PTK2B	0.033	0.073	0.2	42	-9999	42
VEGFR2 homodimer/Frs2	-0.022	0.021	0.098	15	-9999	15
CAV1	-0.005	0.007	0	324	-9999	324
CALM1	-0.013	0.003	0	27	-9999	27
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.015	0.017	-10000	0	-9999	0
endothelial cell proliferation	0.015	0.061	0.21	29	-9999	29
mol:Ca2+	0.028	0.076	0.25	30	-9999	30
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.014	0.018	-10000	0	-9999	0
RP11-342D11.1	-0.015	0.023	0.14	4	-9999	4
CDH5	-0.013	0.003	0	29	-9999	29
VEGFA homodimer	-0.009	0.01	-10000	0	-9999	0
SHC1	-0.013	0.004	0	46	-9999	46
SHC2	-0.014	0	-10000	0	-9999	0
HRAS/GDP	-0.018	0.022	-10000	0	-9999	0
SH2D2A	-0.014	0	-10000	0	-9999	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.015	0.02	-10000	0	-9999	0
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.015	0.017	-10000	0	-9999	0
VEGFR1 homodimer	-0.014	0	-10000	0	-9999	0
SHC/GRB2/SOS1	-0.017	0.021	-10000	0	-9999	0
GRB10	0.021	0.063	0.22	15	-9999	15
PTPN11	-0.014	0	-10000	0	-9999	0
GRB2	-0.014	0.001	0	5	-9999	5
PAK1	-0.014	0	-10000	0	-9999	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.015	0.019	-10000	0	-9999	0
HRAS	-0.014	0.001	0	2	-9999	2
VEGF/Rho/ROCK1/Integrin Complex	0.018	0.033	0.13	15	-9999	15
HIF1A	-0.014	0.001	0	2	-9999	2
FRS2	-0.014	0.001	0	3	-9999	3
oxygen and reactive oxygen species metabolic process	-0.014	0.017	-10000	0	-9999	0
mol:GTP	0	0	-10000	0	-9999	0
FLT4	-0.014	0	-10000	0	-9999	0
Nck/Pak	-0.017	0.002	0	11	-9999	11
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.014	0.016	-10000	0	-9999	0
mol:GDP	-0.017	0.021	-10000	0	-9999	0
mol:NADP	0.024	0.063	0.22	30	-9999	30
eNOS/Hsp90	0.023	0.063	0.21	30	-9999	30
PIK3R1	-0.013	0.004	0	36	-9999	36
mol:IP3	0.028	0.076	0.25	30	-9999	30
HIF1A/ARNT	-0.017	0.001	0	2	-9999	2
SHB	-0.014	0	-10000	0	-9999	0
VEGFA	-0.009	0.009	-10000	0	-9999	0
VEGFC	-0.014	0.002	0	13	-9999	13
FAK1/Vinculin	0.028	0.062	0.18	40	-9999	40
mol:Ca ++	0	0	-10000	0	-9999	0
RHOA	-0.014	0.001	0	2	-9999	2
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.016	0.018	-10000	0	-9999	0
PTPN6	-0.014	0.002	0	11	-9999	11
EPAS1	-0.022	0.016	0.064	15	-9999	15
mol:L-citrulline	0.024	0.063	0.22	30	-9999	30
ITGAV	-0.014	0.002	0	16	-9999	16
PIK3CA	-0.014	0.003	0	25	-9999	25
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.016	0.018	-10000	0	-9999	0
VEGFR2 homodimer/VEGFA homodimer	-0.018	0.02	-10000	0	-9999	0
VEGFR2/3 heterodimer	-0.022	0.021	0.098	15	-9999	15
VEGFB	-0.014	0	-10000	0	-9999	0
MAPK11	0.036	0.081	0.25	40	-9999	40
VEGFR2 homodimer	-0.02	0.026	0.13	15	-9999	15
FLT1	-0.014	0	-10000	0	-9999	0
NEDD4	-0.017	0.014	0.058	16	-9999	16
MAPK3	0.031	0.08	0.25	36	-9999	36
MAPK1	0.031	0.079	0.25	36	-9999	36
VEGFA145/NRP2	-0.009	0.01	-10000	0	-9999	0
VEGFR1/2 heterodimer	-0.022	0.021	0.098	15	-9999	15
KDR	-0.02	0.026	0.13	15	-9999	15
VEGFA165/NRP1/VEGFR2 homodimer	-0.017	0.021	0.074	3	-9999	3
SRC	-0.014	0	-10000	0	-9999	0
platelet activating factor biosynthetic process	0.031	0.08	0.25	36	-9999	36
PI3K	0.003	0.038	0.14	5	-9999	5
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.014	0.016	-10000	0	-9999	0
FES	0.028	0.077	0.25	30	-9999	30
GAB1	0.009	0.037	0.13	3	-9999	3
VEGFR2 homodimer/VEGFA homodimer/Src	-0.015	0.017	-10000	0	-9999	0
CTNNB1	-0.014	0	-10000	0	-9999	0
SOS1	0	0	-10000	0	-9999	0
ARNT	-0.014	0	-10000	0	-9999	0
eNOS/Caveolin-1	0.002	0.035	0.2	6	-9999	6
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.013	0.016	-10000	0	-9999	0
PI3K/GAB1	0.008	0.055	0.19	21	-9999	21
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.017	0.02	-10000	0	-9999	0
PRKACA	-0.014	0	-10000	0	-9999	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.024	0.021	0.094	14	-9999	14
HSP90AA1	-0.014	0	-10000	0	-9999	0
CDC42	0.028	0.077	0.25	30	-9999	30
actin cytoskeleton reorganization	-0.015	0.016	-10000	0	-9999	0
PTK2	0.03	0.061	0.18	40	-9999	40
EDG1	0.029	0.076	0.25	30	-9999	30
mol:DAG	0.028	0.076	0.25	30	-9999	30
CaM/Ca2+	0.014	0.051	0.13	4	-9999	4
MAP2K3	0.028	0.08	0.24	39	-9999	39
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.018	0.021	-10000	0	-9999	0
PLCG1	0.028	0.077	0.25	30	-9999	30
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.016	0.018	-10000	0	-9999	0
IQGAP1	-0.011	0.006	0	127	-9999	127
YES1	-0.012	0.005	0	79	-9999	79
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.015	0.017	-10000	0	-9999	0
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.014	0.016	-10000	0	-9999	0
cell migration	0.037	0.074	0.15	108	-9999	108
mol:PI-3-4-5-P3	0.003	0.037	0.13	5	-9999	5
FYN	-0.014	0.003	0	21	-9999	21
VEGFB/NRP1	0.015	0.051	0.14	4	-9999	4
mol:NO	0.024	0.063	0.22	30	-9999	30
PXN	-0.014	0	-10000	0	-9999	0
HRAS/GTP	-0.018	0.022	-10000	0	-9999	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.018	0.022	0.073	3	-9999	3
VHL	0	0	-10000	0	-9999	0
ITGB3	-0.014	0	-10000	0	-9999	0
NOS3	0.025	0.065	0.23	28	-9999	28
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.015	0.017	-10000	0	-9999	0
RAC1	-0.014	0	-10000	0	-9999	0
PRKCA	0.028	0.079	0.23	39	-9999	39
PRKCB	0.031	0.078	0.24	39	-9999	39
VCL	-0.014	0	-10000	0	-9999	0
VEGFA165/NRP1	-0.015	0.023	0.15	4	-9999	4
VEGFR1/2 heterodimer/VEGFA homodimer	-0.015	0.017	-10000	0	-9999	0
VEGFA165/NRP2	-0.009	0.01	-10000	0	-9999	0
MAPKKK cascade	-0.016	0.03	0.085	1	-9999	1
NRP2	-0.014	0.001	0	1	-9999	1
VEGFC homodimer	-0.014	0.002	0	13	-9999	13
NCK1	-0.014	0.002	0	11	-9999	11
ROCK1	-0.014	0	-10000	0	-9999	0
FAK1/Paxillin	0.028	0.062	0.18	40	-9999	40
MAP3K13	0.028	0.077	0.25	30	-9999	30
PDPK1	0.01	0.056	0.17	35	-9999	35

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.014	0.001	0	3	-10000	0	3
Jak2/Leptin Receptor	0.009	0.021	-10000	0	-10000	0	0
PTP1B/AKT1	0.007	0.026	-10000	0	-0.15	1	1
FYN	-0.014	0.003	0	21	-10000	0	21
p210 bcr-abl/PTP1B	0.009	0.025	-10000	0	-0.15	1	1
EGFR	-0.009	0.007	0.012	6	-10000	0	6
EGF/EGFR	-0.004	0.018	-10000	0	-0.13	1	1
CSF1	-0.014	0	-10000	0	-10000	0	0
AKT1	-0.014	0.001	0	4	-10000	0	4
INSR	-0.014	0.001	0.011	1	-10000	0	1
PTP1B/N-cadherin	0.008	0.026	-10000	0	-0.15	1	1
Insulin Receptor/Insulin	0.003	0.026	-10000	0	-0.15	1	1
HCK	-0.012	0.005	0	86	-10000	0	86
CRK	-0.014	0	-10000	0	-10000	0	0
TYK2	0.003	0.024	0.12	1	-0.15	1	2
EGF	-0.004	0.013	0.012	198	-10000	0	198
YES1	-0.012	0.005	0	79	-10000	0	79
CAV1	0.038	0.034	0.11	18	-10000	0	18
TXN	-0.012	0.006	0.011	37	-10000	0	37
PTP1B/IRS1/GRB2	0.007	0.03	-10000	0	-10000	0	0
cell migration	-0.009	0.025	0.15	1	-10000	0	1
STAT3	-0.014	0.002	0	10	-10000	0	10
PRLR	-0.015	0	-10000	0	-10000	0	0
ITGA2B	-0.014	0	-10000	0	-10000	0	0
CSF1R	-0.013	0.004	0	41	-10000	0	41
Prolactin Receptor/Prolactin	-0.018	0.002	-10000	0	-10000	0	0
FGR	-0.014	0.003	0	17	-10000	0	17
PTP1B/p130 Cas	0.008	0.023	0.092	2	-0.14	1	3
Crk/p130 Cas	0.007	0.026	-10000	0	-0.14	1	1
DOK1	0.003	0.022	-10000	0	-0.14	1	1
JAK2	0.009	0.017	-10000	0	-10000	0	0
Jak2/Leptin Receptor/Leptin	-0.008	0.032	-10000	0	-0.14	1	1
PIK3R1	-0.013	0.004	0	36	-10000	0	36
PTPN1	0.009	0.025	-10000	0	-0.15	1	1
LYN	-0.012	0.005	0	64	-10000	0	64
CDH2	-0.014	0.002	0	16	-10000	0	16
SRC	0.01	0.011	-10000	0	-10000	0	0
ITGB3	-0.014	0	-10000	0	-10000	0	0
CAT1/PTP1B	0.02	0.046	0.13	41	-10000	0	41
CAPN1	-0.014	0.002	0.012	4	-10000	0	4
CSK	-0.014	0	-10000	0	-10000	0	0
PI3K	0	0.027	-10000	0	-10000	0	0
mol:H2O2	0	0.001	-10000	0	-10000	0	0
STAT3 (dimer)	-0.008	0.029	-10000	0	-0.13	1	1
negative regulation of transcription	0.009	0.016	-10000	0	-10000	0	0
FCGR2A	-0.007	0.007	0	265	-10000	0	265
FER	-0.012	0.006	0.011	37	-10000	0	37
alphaIIb/beta3 Integrin	-0.017	0.004	-10000	0	-10000	0	0
BLK	-0.014	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.018	0.007	0.02	4	-10000	0	4
RHOA	-0.014	0.002	0.012	4	-10000	0	4
LEPR	-0.014	0.001	0	3	-10000	0	3
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	-0.014	0.001	0	5	-10000	0	5
mol:NADPH	0.001	0.001	-10000	0	-10000	0	0
TRPV6	0.019	0.048	0.12	66	-0.12	3	69
PRL	-0.015	0.002	-10000	0	-10000	0	0
SOCS3	-0.005	0.001	-10000	0	-10000	0	0
SPRY2	-0.013	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.02	0.004	0.02	4	-10000	0	4
CSF1/CSF1R	0.007	0.03	-10000	0	-0.15	1	1
Ras protein signal transduction	-0.014	0.012	0.18	1	-10000	0	1
IRS1	-0.014	0.001	0	5	-10000	0	5
INS	-0.014	0.001	0.011	1	-10000	0	1
LEP	-0.014	0	-10000	0	-10000	0	0
STAT5B	0.01	0.022	-10000	0	-10000	0	0
STAT5A	0.01	0.022	-10000	0	-10000	0	0
GRB2	-0.014	0.001	0	5	-10000	0	5
PDGFB-D/PDGFRB	0.008	0.027	-10000	0	-0.15	1	1
CSN2	-0.008	0.009	-10000	0	-10000	0	0
PIK3CA	-0.014	0.003	0	25	-10000	0	25
LAT	0.03	0.024	-10000	0	-10000	0	0
YBX1	-0.019	0.003	-10000	0	-10000	0	0
LCK	-0.014	0.001	0	4	-10000	0	4
SHC1	-0.013	0.004	0	46	-10000	0	46
NOX4	-0.011	0.006	0.013	1	-10000	0	1

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.01	0.029	0.092	24	-10000	0	24
BAG4	-0.014	0	-10000	0	-10000	0	0
BAD	-0.003	0.012	-10000	0	-10000	0	0
NFKBIA	-0.014	0.001	0	1	-10000	0	1
BIRC3	-0.013	0.003	0	33	-10000	0	33
BAX	-0.001	0.018	0.11	7	-10000	0	7
EnzymeConsortium:3.1.4.12	0.003	0.009	0.029	24	-10000	0	24
IKBKB	0.005	0.028	0.13	1	-10000	0	1
MAP2K2	-0.012	0.013	0.074	1	-10000	0	1
MAP2K1	-0.011	0.013	0.074	1	-10000	0	1
SMPD1	0.002	0.009	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.01	0.029	0.12	1	-10000	0	1
MAP2K4	-0.007	0.012	0.08	1	-10000	0	1
protein ubiquitination	0.004	0.029	0.13	2	-10000	0	2
EnzymeConsortium:2.7.1.37	-0.014	0.015	0.07	1	-10000	0	1
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.008	0.013	0.081	1	-10000	0	1
CRADD	-0.014	0	-10000	0	-10000	0	0
mol:ceramide	0.002	0.013	0.04	3	-10000	0	3
I-kappa-B-alpha/RELA/p50/ubiquitin	-0.013	0.001	0	1	-10000	0	1
MADD	-0.014	0.001	0	4	-10000	0	4
MAP3K1	-0.003	0.013	0.088	1	-10000	0	1
TRADD	-0.014	0	-10000	0	-10000	0	0
RELA/p50	-0.014	0	-10000	0	-10000	0	0
MAPK3	-0.011	0.013	0.073	1	-10000	0	1
MAPK1	-0.013	0.02	0.073	1	-0.11	12	13
p50/RELA/I-kappa-B-alpha	-0.017	0.001	0	1	-10000	0	1
FADD	0.011	0.029	0.089	25	-10000	0	25
KSR1	-0.003	0.013	-10000	0	-10000	0	0
MAPK8	-0.011	0.014	0.072	2	-10000	0	2
TRAF2	-0.014	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.005	0.028	0.13	1	-10000	0	1
TNF R/SODD	-0.011	0.008	0	183	-10000	0	183
TNF	-0.014	0.001	0	2	-10000	0	2
CYCS	-0.004	0.015	0.076	5	-10000	0	5
IKBKG	0.005	0.028	0.13	1	-10000	0	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.016	0.03	0.099	22	-10000	0	22
RELA	-0.014	0	-10000	0	-10000	0	0
RIPK1	-0.014	0.002	0	9	-10000	0	9
AIFM1	-0.003	0.016	0.079	7	-10000	0	7
TNF/TNF R/SODD	-0.013	0.01	0	185	-10000	0	185
TNFRSF1A	-0.009	0.007	0	183	-10000	0	183
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.014	0.011	-10000	0	-10000	0	0
NSMAF	0.01	0.029	0.088	26	-10000	0	26
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
BCL2	-0.014	0	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.012	0.005	0	65	-9999	65
HDAC3	-0.014	0	-10000	0	-9999	0
VDR	-0.014	0	-10000	0	-9999	0
Cbp/p300/PCAF	-0.014	0	-10000	0	-9999	0
EP300	-0.014	0	-10000	0	-9999	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	-0.006	0.005	-10000	0	-9999	0
KAT2B	0	0	-10000	0	-9999	0
MAPK14	-0.014	0.001	0	2	-9999	2
AKT1	-0.028	0.034	0.083	11	-9999	11
RAR alpha/9cRA/Cyclin H	-0.001	0.031	-10000	0	-9999	0
mol:9cRA	0	0	-10000	0	-9999	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.007	0.004	0.051	3	-9999	3
CDC2	-0.009	0.007	0	193	-9999	193
response to UV	0	0.002	0.022	3	-9999	3
RAR alpha/Jnk1	-0.008	0.005	0.061	3	-9999	3
NCOR2	-0.014	0	-10000	0	-9999	0
VDR/VDR/Vit D3	-0.009	0	-10000	0	-9999	0
RXRs/RARs/NRIP1/9cRA	-0.007	0.025	0.25	3	-9999	3
NCOA2	-0.014	0	-10000	0	-9999	0
NCOA3	-0.014	0.001	0	3	-9999	3
NCOA1	-0.014	0.002	0	14	-9999	14
VDR/VDR/DNA	-0.014	0	-10000	0	-9999	0
RARG	-0.014	0.003	0.028	3	-9999	3
RAR gamma1/9cRA	-0.013	0.003	0.025	3	-9999	3
MAPK3	-0.014	0.003	0.023	3	-9999	3
MAPK1	-0.014	0.003	0	17	-9999	17
MAPK8	-0.014	0.003	0.03	3	-9999	3
mol:Vit D3	0	0	-10000	0	-9999	0
RXRs/VDR/DNA/Vit D3	0.006	0.031	0.21	3	-9999	3
RARA	-0.005	0.006	0.081	3	-9999	3
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-9999	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.007	0.004	0.051	3	-9999	3
PRKCA	-0.014	0.007	0.072	3	-9999	3
RXRs/RARs/NRIP1/9cRA/HDAC1	0.007	0.028	0.29	3	-9999	3
RXRG	-0.008	0.007	0.089	3	-9999	3
RXRA	0.012	0.031	0.18	3	-9999	3
RXRB	-0.008	0.007	0.084	3	-9999	3
VDR/Vit D3/DNA	-0.009	0	-10000	0	-9999	0
RBP1	-0.008	0.007	0	248	-9999	248
CRBP1/9-cic-RA	-0.005	0.004	0	248	-9999	248
RARB	-0.014	0.005	0.051	3	-9999	3
PRKCG	-0.014	0.006	0.069	3	-9999	3
MNAT1	-0.014	0.001	0	1	-9999	1
RAR alpha/RXRs	-0.016	0.039	0.19	3	-9999	3
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.01	0.02	0.16	3	-9999	3
proteasomal ubiquitin-dependent protein catabolic process	-0.007	0.007	0.069	3	-9999	3
RXRs/RARs/NRIP1/9cRA/HDAC3	0.003	0.025	0.28	3	-9999	3
positive regulation of DNA binding	-0.003	0.027	-10000	0	-9999	0
NRIP1	0.004	0.027	0.33	3	-9999	3
RXRs/RARs	0.006	0.022	0.25	3	-9999	3
RXRs/RXRs/DNA/9cRA	0.007	0.028	0.22	3	-9999	3
PRKACA	-0.014	0	-10000	0	-9999	0
CDK7	-0.014	0.001	0	2	-9999	2
TFIIH	-0.02	0.002	0	5	-9999	5
RAR alpha/9cRA	-0.022	0.006	0.054	3	-9999	3
CCNH	-0.014	0.001	0	2	-9999	2
CREBBP	-0.014	0	-10000	0	-9999	0
RAR gamma2/9cRA	-0.03	0.003	-10000	0	-9999	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.014	0.001	0	3	-10000	0	3
mol:S1P	0	0.001	0.025	1	-10000	0	1
S1P1/S1P/Gi	-0.041	0.035	-10000	0	-0.071	294	294
GNAO1	-0.001	0.004	-10000	0	-10000	0	0
S1P/S1P3/G12/G13	-0.012	0.003	0.057	1	-10000	0	1
AKT1	0	0.003	-10000	0	-10000	0	0
AKT3	0.001	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.014	0.001	0	3	-10000	0	3
GNAI2	-0.015	0.002	0.04	1	-10000	0	1
GNAI3	-0.013	0.005	-10000	0	-10000	0	0
GNAI1	-0.012	0.006	0.033	1	-10000	0	1
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0	0.001	0.031	1	-10000	0	1
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	-0.014	0.001	0	4	-10000	0	4
mol:Ca2+	-0.001	0.005	-10000	0	-10000	0	0
MAPK3	-0.001	0.006	-10000	0	-10000	0	0
MAPK1	-0.001	0.006	-10000	0	-10000	0	0
JAK2	-0.015	0.05	0.11	2	-0.14	62	64
CXCR4	-0.001	0.005	-10000	0	-10000	0	0
FLT1	-0.015	0.003	0.06	1	-10000	0	1
RhoA/GDP	-0.009	0.001	0	2	-10000	0	2
Rac1/GDP	-0.009	0	-10000	0	-10000	0	0
SRC	-0.001	0.006	-10000	0	-10000	0	0
S1P/S1P3/Gi	-0.001	0.005	-10000	0	-10000	0	0
RAC1	-0.014	0	-10000	0	-10000	0	0
RhoA/GTP	-0.065	0.038	-10000	0	-0.12	122	122
VEGFA	-0.007	0.008	0.06	1	-10000	0	1
S1P/S1P2/Gi	-0.001	0.005	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	-0.008	0.011	0.14	1	-10000	0	1
RHOA	-0.014	0.001	0	2	-10000	0	2
S1P/S1P3/Gq	-0.008	0.002	0.025	1	-10000	0	1
GNAQ	-0.014	0	-10000	0	-10000	0	0
GNAZ	-0.012	0.005	0.033	1	-10000	0	1
G12/G13	-0.017	0.002	0	6	-10000	0	6
GNA14	-0.014	0.001	0	2	-10000	0	2
GNA15	-0.014	0.002	0	7	-10000	0	7
GNA12	-0.014	0.001	0	4	-10000	0	4
GNA13	-0.014	0.001	0	2	-10000	0	2
GNA11	-0.014	0	-10000	0	-10000	0	0
Rac1/GTP	-0.065	0.038	-10000	0	-0.12	123	123

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	-0.018	0.004	0.068	1	-9999	1
mol:GTP	0	0	-10000	0	-9999	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.017	0.014	0.11	3	-9999	3
ERC1	-0.014	0.001	0	1	-9999	1
RIP2/NOD2	-0.017	0.002	0	9	-9999	9
NFKBIA	-0.029	0.011	0.094	4	-9999	4
BIRC2	-0.014	0	-10000	0	-9999	0
IKBKB	-0.014	0	-10000	0	-9999	0
RIPK2	-0.014	0.001	0	1	-9999	1
IKBKG	-0.005	0.011	0.038	33	-9999	33
IKK complex/A20	-0.013	0.014	-10000	0	-9999	0
NEMO/A20/RIP2	-0.014	0.001	0	1	-9999	1
XPO1	-0.014	0	-10000	0	-9999	0
NEMO/ATM	-0.009	0.014	0.086	1	-9999	1
tumor necrosis factor receptor activity	0	0	-10000	0	-9999	0
RAN	-0.014	0.001	0	3	-9999	3
Exportin 1/RanGTP	-0.013	0.001	0	3	-9999	3
IKK complex/ELKS	-0.017	0.015	-10000	0	-9999	0
BCL10/MALT1/TRAF6	-0.019	0.004	0	27	-9999	27
NOD2	-0.014	0.002	0	8	-9999	8
NFKB1	-0.018	0.004	0.069	1	-9999	1
RELA	-0.018	0.004	0.069	1	-9999	1
MALT1	-0.014	0.003	0	24	-9999	24
cIAP1/UbcH5C	-0.017	0.001	0	1	-9999	1
ATM	-0.014	0.003	0	25	-9999	25
TNF/TNFR1A	-0.011	0.008	0	185	-9999	185
TRAF6	-0.014	0	-10000	0	-9999	0
PRKCA	-0.014	0	-10000	0	-9999	0
CHUK	-0.014	0.001	0	1	-9999	1
UBE2D3	-0.014	0.001	0	1	-9999	1
TNF	-0.014	0.001	0	2	-9999	2
NF kappa B1 p50/RelA	-0.028	0.003	0	5	-9999	5
BCL10	-0.014	0.001	0	4	-9999	4
proteasomal ubiquitin-dependent protein catabolic process	-0.029	0.011	0.094	4	-9999	4
beta TrCP1/SCF ubiquitin ligase complex	-0.018	0.004	0.069	1	-9999	1
TNFRSF1A	-0.009	0.007	0	183	-9999	183
IKK complex	-0.013	0.016	0.087	1	-9999	1
CYLD	-0.014	0	-10000	0	-9999	0
IKK complex/PKC alpha	-0.017	0.018	0.083	2	-9999	2

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.017	0.014	-10000	0	-0.054	21	21
KIRREL	-0.015	0.009	0.027	22	-10000	0	22
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.017	0.014	0.054	21	-10000	0	21
PLCG1	-0.014	0	-10000	0	-10000	0	0
ARRB2	-0.014	0	-10000	0	-10000	0	0
WASL	-0.014	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.02	0.016	0.092	8	-10000	0	8
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.01	0.014	0.051	20	-10000	0	20
FYN	-0.017	0.007	0.075	2	-10000	0	2
mol:Ca2+	-0.019	0.023	0.094	21	-10000	0	21
mol:DAG	-0.019	0.024	0.096	21	-10000	0	21
NPHS2	-0.015	0.009	0.027	23	-10000	0	23
mol:IP3	-0.019	0.024	0.096	21	-10000	0	21
regulation of endocytosis	-0.021	0.004	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/Cholesterol	-0.013	0.022	0.093	21	-10000	0	21
establishment of cell polarity	-0.017	0.014	0.054	21	-10000	0	21
Nephrin/NEPH1/podocin/NCK1-2	-0.022	0.026	0.11	20	-10000	0	20
Nephrin/NEPH1/beta Arrestin2	-0.021	0.007	0.071	2	-10000	0	2
NPHS1	-0.015	0.009	0.027	22	-10000	0	22
Nephrin/NEPH1/podocin	-0.017	0.008	0.093	2	-10000	0	2
TJP1	-0.014	0	-10000	0	-10000	0	0
NCK1	-0.014	0.002	0	11	-10000	0	11
NCK2	-0.014	0.001	0	1	-10000	0	1
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.019	0.024	0.098	21	-10000	0	21
CD2AP	-0.013	0.004	0	49	-10000	0	49
Nephrin/NEPH1/podocin/GRB2	-0.02	0.022	0.098	18	-10000	0	18
GRB2	-0.014	0.001	0	5	-10000	0	5
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.019	0.01	0.074	2	-10000	0	2
cytoskeleton organization	-0.019	0.017	0.08	12	-10000	0	12
Nephrin/NEPH1	-0.01	0.011	0.045	21	-10000	0	21
Nephrin/NEPH1/ZO-1	-0.019	0.015	0.053	21	-10000	0	21

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.02	0.043	0.23	15	-10000	0	15
IHH	-0.019	0.022	0.084	22	-10000	0	22
SHH Np/Cholesterol/GAS1	-0.016	0.006	0	58	-10000	0	58
LRPAP1	-0.014	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.016	0.006	-10000	0	0	58	58
SMO/beta Arrestin2	-0.013	0.035	0.16	22	-10000	0	22
SMO	-0.009	0.037	0.17	22	-10000	0	22
AKT1	-0.01	0.052	-10000	0	-0.21	29	29
ARRB2	-0.014	0	-10000	0	-10000	0	0
BOC	0	0	-10000	0	-10000	0	0
ADRBK1	-0.014	0	-10000	0	-10000	0	0
heart looping	-0.009	0.036	0.16	22	-10000	0	22
STIL	-0.022	0.033	0.14	18	-10000	0	18
DHH N/PTCH2	-0.009	0	-10000	0	-10000	0	0
DHH N/PTCH1	-0.018	0.022	0.16	8	-10000	0	8
PIK3CA	-0.014	0.003	0	25	-10000	0	25
DHH	0	0	-10000	0	-10000	0	0
PTHLH	-0.017	0.028	0.22	7	-10000	0	7
determination of left/right symmetry	-0.009	0.036	0.16	22	-10000	0	22
PIK3R1	-0.013	0.004	0	36	-10000	0	36
skeletal system development	-0.017	0.028	0.22	7	-10000	0	7
IHH N/Hhip	-0.008	0.013	0.054	22	-10000	0	22
DHH N/Hhip	0	0	-10000	0	-10000	0	0
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.009	0.036	0.16	22	-10000	0	22
pancreas development	0	0	-10000	0	-10000	0	0
HHAT	-0.014	0	-10000	0	-10000	0	0
PI3K	-0.015	0.005	0	60	-10000	0	60
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.013	0.004	0	58	-10000	0	58
somite specification	-0.009	0.036	0.16	22	-10000	0	22
SHH Np/Cholesterol/PTCH1	-0.025	0.021	0.14	8	-10000	0	8
SHH Np/Cholesterol/PTCH2	-0.018	0	-10000	0	-10000	0	0
SHH Np/Cholesterol/Megalin	-0.018	0.001	0	1	-10000	0	1
SHH	-0.017	0	-10000	0	-10000	0	0
catabolic process	-0.019	0.035	0.19	15	-10000	0	15
SMO/Vitamin D3	-0.023	0.023	0.16	8	-10000	0	8
SHH Np/Cholesterol/Hhip	-0.012	0	-10000	0	-10000	0	0
LRP2	-0.014	0.001	0	1	-10000	0	1
receptor-mediated endocytosis	-0.021	0.033	0.14	22	-10000	0	22
SHH Np/Cholesterol/BOC	-0.012	0	-10000	0	-10000	0	0
SHH Np/Cholesterol/CDO	-0.018	0	-10000	0	-10000	0	0
mesenchymal cell differentiation	0.012	0	-10000	0	-10000	0	0
mol:Vitamin D3	-0.025	0.024	0.16	8	-10000	0	8
IHH N/PTCH2	-0.017	0.016	0.06	22	-10000	0	22
CDON	-0.014	0	-10000	0	-10000	0	0
IHH N/PTCH1	-0.021	0.029	0.22	8	-10000	0	8
Megalin/LRPAP1	-0.017	0.001	0	1	-10000	0	1
PTCH2	-0.014	0	-10000	0	-10000	0	0
SHH Np/Cholesterol	-0.012	0	-10000	0	-10000	0	0
PTCH1	-0.019	0.035	0.19	15	-10000	0	15
HHIP	0	0	-10000	0	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	-0.014	0	-9999	0	-9999	0
Aurora C/Aurora B/INCENP	-0.017	0.004	0	29	-9999	29
metaphase	0	0	-9999	0	-9999	0
mitosis	0	0	-9999	0	-9999	0
H3F3B	-0.005	0.001	0	29	-9999	29
AURKB	-0.013	0.003	0	27	-9999	27
AURKC	-0.014	0.001	0	2	-9999	2

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.013	0.002	0	15	-10000	0	15
SNTA1	-0.014	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.02	0.003	0	16	-10000	0	16
MAPK12	-0.015	0.002	-10000	0	-10000	0	0
CCND1	-0.004	0.002	-10000	0	-10000	0	0
p38 gamma/SNTA1	-0.018	0.01	0.053	10	-10000	0	10
MAP2K3	-0.014	0	-10000	0	-10000	0	0
PKN1	-0.014	0.002	0	10	-10000	0	10
G2/M transition checkpoint	-0.015	0.002	-10000	0	-10000	0	0
MAP2K6	-0.011	0.001	-10000	0	-10000	0	0
MAPT	-0.034	0.044	0.066	1	-0.12	115	116
MAPK13	-0.017	0.003	0	15	-10000	0	15
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	-0.005	0.001	0	10	-10000	0	10

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.017	0	-10000	0	-9999	0
FBXW11	-0.014	0	-10000	0	-9999	0
NF kappa B1 p50/c-Rel	-0.02	0.002	0	4	-9999	4
NF kappa B1 p50/RelA/I kappa B alpha	-0.016	0.018	0.048	37	-9999	37
NFKBIA	-0.003	0.015	0.051	37	-9999	37
MAPK14	-0.014	0.001	0	2	-9999	2
NF kappa B1 p105/p50	-0.02	0.002	0	4	-9999	4
ARRB2	-0.005	0	-10000	0	-9999	0
REL	-0.014	0	-10000	0	-9999	0
response to oxidative stress	0	0	-10000	0	-9999	0
BCL3/NF kappa B1 p50	-0.02	0.002	0	4	-9999	4
response to UV	0	0	-10000	0	-9999	0
NF kappa B1 p105/RelA	-0.02	0.002	0	4	-9999	4
PIK3CA	-0.014	0.003	0	25	-9999	25
NF kappa B1 p50 dimer	-0.016	0.013	0.13	4	-9999	4
PIK3R1	-0.013	0.004	0	36	-9999	36
NFKB1	-0.017	0.001	0	4	-9999	4
RELA	-0.014	0	-10000	0	-9999	0
positive regulation of anti-apoptosis	-0.009	0.005	0.047	4	-9999	4
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.018	0.018	0.047	37	-9999	37
SRC	-0.014	0	-10000	0	-9999	0
PI3K	-0.015	0.005	0	60	-9999	60
NF kappa B1 p50/RelA	-0.009	0.005	0.047	4	-9999	4
IKBKB	-0.014	0	-10000	0	-9999	0
beta TrCP1/SCF ubiquitin ligase complex	-0.014	0	-10000	0	-9999	0
SYK	-0.013	0.004	0	36	-9999	36
I kappa B alpha/PIK3R1	-0.007	0.016	0.054	32	-9999	32
cell death	-0.017	0.018	0.046	37	-9999	37
NF kappa B1 p105/c-Rel	-0.02	0.002	0	4	-9999	4
LCK	-0.014	0.001	0	4	-9999	4
BCL3	-0.014	0	-10000	0	-9999	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.014	0.001	0	4	-10000	0	4
ANTXR2	0	0	-10000	0	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.001	0	0	4	-10000	0	4
monocyte activation	0.001	0.002	-10000	0	-10000	0	0
MAP2K2	0.004	0	-10000	0	-10000	0	0
MAP2K1	-0.007	0.001	0	17	-10000	0	17
MAP2K7	-0.007	0.001	0	4	-10000	0	4
MAP2K6	-0.007	0.001	0	4	-10000	0	4
CYAA	-0.005	0	0	4	-10000	0	4
MAP2K4	-0.006	0.001	0	25	-10000	0	25
IL1B	-0.005	0.012	0.1	6	-10000	0	6
Channel	-0.006	0.001	0	4	-10000	0	4
NLRP1	-0.007	0.001	0	4	-10000	0	4
CALM1	-0.013	0.003	0	27	-10000	0	27
negative regulation of phagocytosis	-0.017	0.08	-10000	0	-0.36	27	27
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.001	0	-10000	0	0	4	4
MAPK3	-0.007	0.001	0	4	-10000	0	4
MAPK1	-0.007	0.001	0	21	-10000	0	21
PGR	-0.007	0.001	0	4	-10000	0	4
PA/Cellular Receptors	-0.007	0.001	0	4	-10000	0	4
apoptosis	-0.001	0	0	4	-10000	0	4
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.005	0	-10000	0	0	4	4
macrophage activation	-0.011	0.002	-10000	0	-10000	0	0
TNF	-0.014	0.001	0	2	-10000	0	2
VCAM1	0.001	0.002	-10000	0	-10000	0	0
platelet activation	-0.017	0.08	-10000	0	-0.36	27	27
MAPKKK cascade	0.007	0.003	-10000	0	-10000	0	0
IL18	-0.003	0.016	0.1	12	-10000	0	12
negative regulation of macrophage activation	-0.001	0	0	4	-10000	0	4
LEF	-0.001	0	0	4	-10000	0	4
CASP1	-0.002	0.002	0	174	-10000	0	174
mol:cAMP	-0.017	0.08	-10000	0	-0.36	27	27
necrosis	-0.001	0	0	4	-10000	0	4
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.005	0	0	4	-10000	0	4
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Nectin adhesion 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
PDGFRB	-0.014	0.001	0	3	-10000	0	3
alphaV beta3 Integrin	-0.017	0.003	0	16	-10000	0	16
PTK2	-0.006	0.018	-10000	0	-10000	0	0
positive regulation of JNK cascade	0.006	0.007	-10000	0	-10000	0	0
CDC42/GDP	0.009	0.012	-10000	0	-10000	0	0
Rac1/GDP	0.008	0.012	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	-0.014	0	-10000	0	-10000	0	0
CTNNB1	-0.014	0	-10000	0	-10000	0	0
CDC42/GTP	0.009	0.01	-10000	0	-10000	0	0
nectin-3/I-afadin	-0.017	0.001	0	2	-10000	0	2
RAPGEF1	-0.005	0.013	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0.012	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.014	0.001	0	3	-10000	0	3
TLN1	-0.006	0.031	0.094	46	-10000	0	46
Rap1/GTP	-0.008	0.009	-10000	0	-10000	0	0
IQGAP1	-0.011	0.006	0	127	-10000	0	127
Rap1/GTP/I-afadin	-0.012	0	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.017	0.001	0	2	-10000	0	2
PVR	-0.014	0	-10000	0	-10000	0	0
Necl-5(dimer)	-0.014	0	-10000	0	-10000	0	0
mol:GDP	0.004	0.013	-10000	0	-10000	0	0
MLLT4	-0.014	0	-10000	0	-10000	0	0
PIK3CA	-0.014	0.003	0	25	-10000	0	25
PI3K	-0.024	0.009	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.017	0	-10000	0	-10000	0	0
positive regulation of lamellipodium assembly	0.008	0.008	-10000	0	-10000	0	0
PVRL1	-0.014	0	-10000	0	-10000	0	0
PVRL3	-0.014	0.001	0	2	-10000	0	2
PVRL2	-0.014	0	-10000	0	-10000	0	0
PIK3R1	-0.013	0.004	0	36	-10000	0	36
CDH1	-0.014	0.002	0	8	-10000	0	8
CLDN1	-0.014	0.002	0	9	-10000	0	9
JAM-A/CLDN1	-0.022	0.006	0	36	-10000	0	36
SRC	0.007	0.009	-10000	0	-10000	0	0
ITGB3	-0.014	0	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin	-0.017	0	-10000	0	-10000	0	0
FARP2	0.008	0.013	-10000	0	-10000	0	0
RAC1	-0.014	0	-10000	0	-10000	0	0
CTNNA1	-0.014	0	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.02	0.001	0	2	-10000	0	2
nectin-1/I-afadin	-0.017	0	-10000	0	-10000	0	0
nectin-2/I-afadin	-0.017	0	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	-0.01	0.006	0	127	-10000	0	127
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.02	0.001	0	2	-10000	0	2
CDC42/GTP/IQGAP1/filamentous actin	-0.01	0.006	0	127	-10000	0	127
F11R	-0.013	0.003	0	34	-10000	0	34
positive regulation of filopodium formation	0.006	0.007	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.015	0.035	0.09	41	-0.1	10	51
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.017	0	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	-0.017	0	-10000	0	-10000	0	0
PIP5K1C	-0.012	0.003	0	32	-10000	0	32
VAV2	0.009	0.013	-10000	0	-10000	0	0
RAP1/GDP	-0.002	0.012	-10000	0	-10000	0	0
ITGAV	-0.014	0.002	0	16	-10000	0	16
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.02	0.001	0	2	-10000	0	2
nectin-3(dimer)/I-afadin/I-afadin	-0.017	0.001	0	2	-10000	0	2
Rac1/GTP	0.01	0.011	-10000	0	-10000	0	0
PTPRM	-0.007	0.001	0	12	-10000	0	12
E-cadherin/beta catenin/alpha catenin	-0.031	0.004	-10000	0	-10000	0	0
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	-0.014	0	-10000	0	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.021	0.02	0.13	3	-9999	3
NFATC2	-0.015	0.018	0.066	14	-9999	14
NFATC3	-0.021	0.02	0.13	3	-9999	3
CD40LG	-0.047	0.083	0.24	30	-9999	30
PTGS2	-0.059	0.05	0.2	4	-9999	4
JUNB	-0.014	0.002	0	8	-9999	8
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.014	0.011	0.029	27	-9999	27
CaM/Ca2+	-0.014	0.011	0.029	27	-9999	27
CALM1	-0.016	0.011	0.045	3	-9999	3
JUN	-0.017	0.011	0.044	3	-9999	3
mol:Ca2+	-0.005	0.004	0.012	30	-9999	30
Calcineurin A alpha-beta B1/FKBP12/FK506	-0.008	0.006	0.029	3	-9999	3
FOSL1	-0.014	0.002	0	13	-9999	13
CREM	-0.014	0	-10000	0	-9999	0
Jun/NFAT1-c-4/p21SNFT	-0.051	0.047	0.14	27	-9999	27
FOS	-0.013	0.011	0.042	2	-9999	2
IFNG	-0.047	0.083	0.24	29	-9999	29
AP-1/NFAT1-c-4	-0.056	0.065	0.2	16	-9999	16
FASLG	-0.047	0.083	0.3	14	-9999	14
NFAT1-c-4/ICER1	-0.038	0.039	0.13	13	-9999	13
IL2RA	-0.05	0.072	0.26	10	-9999	10
FKBP12/FK506	-0.009	0	0	1	-9999	1
CSF2	-0.047	0.083	0.24	30	-9999	30
JunB/Fra1/NFAT1-c-4	-0.04	0.037	0.11	24	-9999	24
IL4	-0.047	0.083	0.24	30	-9999	30
IL2	-0.006	0.005	-10000	0	-9999	0
IL3	-0.009	0.007	-10000	0	-9999	0
FKBP1A	-0.014	0.001	0	1	-9999	1
BATF3	0	0	-10000	0	-9999	0
mol:FK506	0	0	-10000	0	-9999	0
POU2F1	-0.015	0	-10000	0	-9999	0

×

Arf6 trafficking events

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
SLC2A4	-0.014	0	-10000	0	-9999	0	0
CLTC	0.001	0.007	-10000	0	-9999	0	0
calcium ion-dependent exocytosis	0	0.016	0.098	1	-9999	0	1
Dynamin 2/GTP	-0.012	0	-10000	0	-9999	0	0
EXOC4	0	0	-10000	0	-9999	0	0
CD59	-0.001	0.009	-10000	0	-9999	0	0
CPE	-0.012	0.004	0	45	-9999	0	45
CTNNB1	-0.014	0	-10000	0	-9999	0	0
membrane fusion	-0.001	0.017	0.055	44	-9999	0	44
CTNND1	-0.016	0.002	-10000	0	-9999	0	0
DNM2	-0.014	0	-10000	0	-9999	0	0
mol:PI-4-5-P2	-0.003	0.011	0.063	1	-9999	0	1
TSHR	-0.013	0.001	0	4	-9999	0	4
INS	0.002	0.006	-10000	0	-9999	0	0
BIN1	-0.013	0.004	0	41	-9999	0	41
mol:Choline	-0.001	0.017	0.055	44	-9999	0	44
growth hormone secretagogue receptor activity	0	0	-10000	0	-9999	0	0
mol:GDP	-0.007	0	-10000	0	-9999	0	0
membrane depolarization	0	0	-10000	0	-9999	0	0
ARF6	-0.014	0	-10000	0	-9999	0	0
mol:Ca2+	-0.012	0	-10000	0	-9999	0	0
JUP	0	0.013	-10000	0	-9999	0	0
ASAP2/amphiphysin II	-0.011	0.003	0	41	-9999	0	41
ARF6/GTP	-0.009	0	-10000	0	-9999	0	0
CDH1	-0.001	0.012	-10000	0	-9999	0	0
clathrin-independent pinocytosis	-0.009	0	-10000	0	-9999	0	0
MAPK8IP3	-0.014	0	-10000	0	-9999	0	0
positive regulation of endocytosis	-0.009	0	-10000	0	-9999	0	0
EXOC2	-0.014	0	-10000	0	-9999	0	0
substrate adhesion-dependent cell spreading	-0.007	0.002	-10000	0	-9999	0	0
insulin receptor binding	0	0	-10000	0	-9999	0	0
SPAG9	-0.014	0.001	0	1	-9999	0	1
regulation of calcium-dependent cell-cell adhesion	0.009	0.012	-10000	0	-9999	0	0
positive regulation of phagocytosis	-0.013	0.001	0	1	-9999	0	1
ARF6/GTP/JIP3	-0.014	0	-10000	0	-9999	0	0
ACAP1	0.001	0.016	0.052	44	-9999	0	44
mol:GTP	0	0	-10000	0	-9999	0	0
CHRM2	-0.001	0.009	-10000	0	-9999	0	0
clathrin heavy chain/ACAP1	-0.002	0.014	-10000	0	-9999	0	0
JIP4/KLC1	-0.013	0.008	0	139	-9999	0	139
EXOC1	-0.014	0.002	0	8	-9999	0	8
exocyst	-0.007	0.002	-10000	0	-9999	0	0
RALA/GTP	-0.008	0.002	0	45	-9999	0	45
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	-0.013	0.001	0	1	-9999	0	1
receptor recycling	-0.009	0	-10000	0	-9999	0	0
CTNNA1	-0.016	0	-10000	0	-9999	0	0
NME1	-0.007	0	-10000	0	-9999	0	0
clathrin coat assembly	0	0.009	-10000	0	-9999	0	0
IL2RA	-0.001	0.011	-10000	0	-9999	0	0
VAMP3	-0.013	0.001	0	1	-9999	0	1
GLUT4/clathrin heavy chain/ACAP1	-0.006	0.015	-10000	0	-9999	0	0
EXOC6	0	0	-10000	0	-9999	0	0
PLD1	-0.004	0.001	-10000	0	-9999	0	0
PLD2	-0.004	0.001	0	45	-9999	0	45
EXOC5	-0.014	0.003	0	17	-9999	0	17
PIP5K1C	-0.003	0.011	-10000	0	-9999	0	0
SDC1	0.003	0.018	-10000	0	-9999	0	0
ARF6/GDP	-0.007	0	-10000	0	-9999	0	0
EXOC7	-0.014	0	-10000	0	-9999	0	0
E-cadherin/beta catenin	-0.009	0.013	-10000	0	-9999	0	0
mol:Phosphatidic acid	-0.001	0.017	0.055	44	-9999	0	44
endocytosis	0.011	0.003	-10000	0	0	41	41
SCAMP2	-0.014	0	-10000	0	-9999	0	0
ADRB2	-0.005	0.01	-10000	0	-9999	0	0
EXOC3	-0.014	0	-10000	0	-9999	0	0
ASAP2	0	0	-10000	0	-9999	0	0
Dynamin 2/GDP	-0.012	0	-10000	0	-9999	0	0
KLC1	-0.01	0.006	0	138	-9999	0	138
AVPR2	-0.005	0.008	-10000	0	-9999	0	0
RALA	-0.013	0.004	0	45	-9999	0	45
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.016	0.019	0.087	10	-9999	0	10

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	-0.012	0.005	0	65	-10000	0	65
HDAC2	-0.014	0.001	0	5	-10000	0	5
GNB1/GNG2	-0.013	0.005	0.023	11	-10000	0	11
forebrain development	-0.036	0.044	0.27	7	-10000	0	7
GNAO1	-0.001	0.004	0.018	1	-10000	0	1
SMO/beta Arrestin2	-0.016	0.009	0.046	11	-10000	0	11
SMO	-0.014	0.006	0.026	11	-10000	0	11
ARRB2	-0.014	0.005	0.019	11	-10000	0	11
GLI3/SPOP	-0.015	0.038	-10000	0	-0.13	47	47
mol:GTP	0	0.001	0.008	11	-10000	0	11
GSK3B	-0.014	0.001	0	4	-10000	0	4
GNAI2	-0.014	0.005	0.018	11	-10000	0	11
SIN3/HDAC complex	-0.018	0.001	-10000	0	-10000	0	0
GNAI1	-0.012	0.007	0.017	11	-10000	0	11
XPO1	-0.014	0.009	0.045	11	-10000	0	11
GLI1/Su(fu)	-0.027	0.027	0.2	3	-10000	0	3
SAP30	-0.014	0	-10000	0	-10000	0	0
mol:GDP	-0.014	0.006	0.026	11	-10000	0	11
MIM/GLI2A	-0.014	0.013	0.14	4	-10000	0	4
IFT88	-0.014	0	-10000	0	-10000	0	0
GNAI3	-0.012	0.006	0.016	7	-10000	0	7
GLI2	-0.009	0.008	-10000	0	-0.14	1	1
GLI3	-0.012	0.038	-10000	0	-0.13	47	47
CSNK1D	-0.014	0.001	0	2	-10000	0	2
CSNK1E	-0.014	0.001	0	1	-10000	0	1
SAP18	-0.014	0	-10000	0	-10000	0	0
embryonic digit morphogenesis	-0.014	0	-10000	0	-10000	0	0
GNG2	0	0	-10000	0	-10000	0	0
Gi family/GTP	-0.001	0.006	0.052	4	-0.072	1	5
SIN3B	-0.014	0	-10000	0	-10000	0	0
SIN3A	0	0	-10000	0	-10000	0	0
GLI3/Su(fu)	-0.015	0.028	-10000	0	-0.099	44	44
GLI2/Su(fu)	-0.012	0.008	-10000	0	-0.12	1	1
FOXA2	-0.009	0.027	0.3	4	-10000	0	4
neural tube patterning	-0.036	0.044	0.27	7	-10000	0	7
SPOP	-0.014	0	-10000	0	-10000	0	0
Su(fu)/PIAS1	-0.01	0.006	0.033	8	-10000	0	8
GNB1	-0.014	0.002	0	6	-10000	0	6
CSNK1G2	-0.014	0	-10000	0	-10000	0	0
CSNK1G3	-0.014	0	-10000	0	-10000	0	0
MTSS1	-0.014	0.013	0.14	4	-10000	0	4
embryonic limb morphogenesis	-0.036	0.044	0.27	7	-10000	0	7
SUFU	-0.006	0.005	0.025	11	-10000	0	11
LGALS3	-0.012	0.005	0	72	-10000	0	72
catabolic process	-0.02	0.036	-10000	0	-0.19	6	6
GLI3A/CBP	-0.02	0.006	0.024	7	-10000	0	7
KIF3A	-0.013	0.004	0	49	-10000	0	49
GLI1	-0.039	0.039	0.32	4	-10000	0	4
RAB23	-0.014	0.001	0	5	-10000	0	5
CSNK1A1	-0.014	0	-10000	0	-10000	0	0
IFT172	0	0	-10000	0	-10000	0	0
RBBP7	-0.014	0	-10000	0	-10000	0	0
Su(fu)/Galectin3	-0.009	0.006	0.03	5	-10000	0	5
GNAZ	-0.012	0.006	0.018	7	-10000	0	7
RBBP4	-0.012	0.006	0	100	-10000	0	100
CSNK1G1	-0.014	0	-10000	0	-10000	0	0
PIAS1	-0.014	0	-10000	0	-10000	0	0
PRKACA	-0.014	0	-10000	0	-10000	0	0
GLI2/SPOP	-0.014	0.008	-10000	0	-0.13	1	1
STK36	0	0.005	0.036	11	-10000	0	11
Gi family/GNB1/GNG2/GDP	-0.001	0.003	-10000	0	-10000	0	0
PTCH1	-0.034	0.05	0.34	7	-10000	0	7
MIM/GLI1	-0.042	0.046	0.24	10	-10000	0	10
CREBBP	-0.02	0.006	0.024	7	-10000	0	7
Su(fu)/SIN3/HDAC complex	0.008	0.025	0.09	17	-10000	0	17

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.011	0.031	0.18	2	-9999	2
CRKL	-0.025	0.02	0.086	11	-9999	11
mol:DAG	-0.013	0.026	-10000	0	-9999	0
HRAS	-0.025	0.036	0.14	8	-9999	8
MAPK8	-0.011	0.04	0.096	64	-9999	64
RAP1A	-0.025	0.02	0.086	11	-9999	11
GAB1	-0.025	0.02	0.086	11	-9999	11
MAPK14	-0.011	0.04	0.096	64	-9999	64
EPO	-0.016	0.007	0.026	2	-9999	2
PLCG1	-0.013	0.026	-10000	0	-9999	0
EPOR/TRPC2/IP3 Receptors	-0.016	0.007	0.026	2	-9999	2
RAPGEF1	-0.014	0	-10000	0	-9999	0
EPO/EPOR (dimer)/SOCS3	-0.021	0.01	0.045	2	-9999	2
GAB1/SHC/GRB2/SOS1	-0.03	0.017	0.061	9	-9999	9
EPO/EPOR (dimer)	-0.019	0.009	0.044	2	-9999	2
IRS2	-0.025	0.02	0.088	10	-9999	10
STAT1	-0.015	0.025	-10000	0	-9999	0
STAT5B	-0.014	0.026	-10000	0	-9999	0
cell proliferation	-0.014	0.039	0.09	64	-9999	64
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.032	0.017	0.046	6	-9999	6
TEC	-0.025	0.02	0.086	11	-9999	11
SOCS3	-0.014	0	-10000	0	-9999	0
STAT1 (dimer)	-0.015	0.025	-10000	0	-9999	0
JAK2	-0.016	0.007	0.017	19	-9999	19
PIK3R1	-0.013	0.004	0	36	-9999	36
EPO/EPOR (dimer)/JAK2	-0.023	0.016	-10000	0	-9999	0
EPO/EPOR	-0.019	0.009	0.044	2	-9999	2
LYN	-0.013	0.005	-10000	0	-9999	0
TEC/VAV2	-0.029	0.021	0.086	11	-9999	11
elevation of cytosolic calcium ion concentration	-0.016	0.007	0.026	2	-9999	2
SHC1	-0.013	0.004	0	46	-9999	46
EPO/EPOR (dimer)/LYN	-0.02	0.009	-10000	0	-9999	0
mol:IP3	-0.013	0.026	-10000	0	-9999	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.027	0.02	0.083	9	-9999	9
SH2B3	-0.017	0.005	0.017	9	-9999	9
NFKB1	-0.011	0.039	0.096	62	-9999	62
EPO/EPOR (dimer)/JAK2/SOCS3	-0.006	0.001	-10000	0	-9999	0
PTPN6	-0.023	0.012	0.073	8	-9999	8
TEC/VAV2/GRB2	-0.033	0.022	0.086	11	-9999	11
EPOR	-0.016	0.007	0.026	2	-9999	2
INPP5D	0	0	-10000	0	-9999	0
mol:GDP	-0.03	0.017	0.061	9	-9999	9
SOS1	0	0	-10000	0	-9999	0
PLCG2	-0.014	0.002	0	10	-9999	10
CRKL/CBL/C3G	-0.033	0.021	0.086	11	-9999	11
VAV2	-0.025	0.02	0.086	11	-9999	11
CBL	-0.025	0.02	0.086	11	-9999	11
SHC/Grb2/SOS1	-0.028	0.01	-10000	0	-9999	0
STAT5A	-0.014	0.026	-10000	0	-9999	0
GRB2	-0.014	0.001	0	5	-9999	5
STAT5 (dimer)	-0.022	0.028	-10000	0	-9999	0
LYN/PLCgamma2	-0.015	0.006	-10000	0	-9999	0
PTPN11	-0.014	0	-10000	0	-9999	0
BTK	-0.025	0.02	0.088	10	-9999	10
BCL2	-0.011	0.031	0.18	2	-9999	2

×

Signaling events mediated by HDAC Class III

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
EP300	-0.014	0	-10000	0	-9999	0	0
HDAC4	-0.014	0	-10000	0	-9999	0	0
induction of apoptosis	0	0	-10000	0	-9999	0	0
regulation of S phase of mitotic cell cycle	0.009	0.003	-10000	0	-9999	0	0
CDKN1A	-0.006	0.003	0	112	-9999	0	112
KAT2B	0	0	-10000	0	-9999	0	0
BAX	-0.014	0.002	0	7	-9999	0	7
FOXO3	0.004	0.001	-10000	0	-9999	0	0
FOXO1	-0.014	0.002	0	11	-9999	0	11
FOXO4	-0.005	0	-10000	0	-9999	0	0
response to UV	0	0	-10000	0	-9999	0	0
XRCC6	-0.014	0	-10000	0	-9999	0	0
TAT	-0.014	0	-10000	0	-9999	0	0
mol:Lysophosphatidic acid	0	0	-10000	0	-9999	0	0
MYOD1	-0.009	0	-10000	0	-9999	0	0
PPARGC1A	-0.014	0.001	0	3	-9999	0	3
FHL2	-0.014	0.003	0	26	-9999	0	26
response to nutrient levels	0	0	-10000	0	-9999	0	0
KU70/SIRT1	-0.019	0.001	-10000	0	-9999	0	0
HIST2H4A	-0.009	0.003	-10000	0	-9999	0	0
SIRT1/FOXO3a	-0.009	0.003	-10000	0	-9999	0	0
SIRT1	-0.015	0.005	-10000	0	-9999	0	0
response to hypoxia	0	0	-10000	0	-9999	0	0
SIRT1/MEF2D/HDAC4	-0.022	0	-10000	0	-9999	0	0
SIRT1/Histone H1b	-0.011	0.005	0.057	1	-9999	0	1
apoptosis	0.021	0.003	-10000	0	0	7	7
SIRT1/PGC1A	-0.015	0.001	0	3	-9999	0	3
p53/SIRT1	-0.017	0.009	0	112	-9999	0	112
SIRT1/FOXO4	-0.011	0.004	-10000	0	-9999	0	0
FOXO1/FHL2/SIRT1	-0.018	0.005	0	37	-9999	0	37
HIST1H1E	-0.005	0	0	1	-9999	0	1
SIRT1/p300	-0.019	0.001	-10000	0	-9999	0	0
muscle cell differentiation	0.015	0	-10000	0	-9999	0	0
TP53	-0.013	0.007	0	112	-9999	0	112
KU70/SIRT1/BAX	-0.021	0.003	0	7	-9999	0	7
CREBBP	-0.014	0	-10000	0	-9999	0	0
MEF2D	-0.014	0	-10000	0	-9999	0	0
HIV-1 Tat/SIRT1	-0.019	0.001	-10000	0	-9999	0	0
ACSS2	-0.009	0.003	-10000	0	-9999	0	0
SIRT1/PCAF/MYOD	-0.015	0	-10000	0	-9999	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.014	0	-10000	0	-10000	0	0
NFATC1	-0.01	0.011	-10000	0	-10000	0	0
NFATC2	-0.002	0.016	-10000	0	-0.084	3	3
NFATC3	-0.005	0.001	-10000	0	-10000	0	0
YWHAE	-0.014	0.001	0	2	-10000	0	2
Calcineurin A alpha-beta B1/CABIN1	-0.065	0.015	-10000	0	-10000	0	0
Exportin 1/Ran/NUP214	-0.02	0.002	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.068	0.017	-10000	0	-10000	0	0
BCL2/BAX	-0.017	0.002	0	7	-10000	0	7
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.009	0.002	-10000	0	-10000	0	0
CaM/Ca2+	-0.009	0.002	-10000	0	-10000	0	0
BAX	-0.014	0.002	0	7	-10000	0	7
MAPK14	-0.014	0.001	-10000	0	-10000	0	0
BAD	-0.014	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.067	0.014	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/BCL2	-0.014	0	-10000	0	-10000	0	0
FKBP8	-0.014	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.066	0.014	-10000	0	-10000	0	0
KPNB1	-0.014	0	-10000	0	-10000	0	0
KPNA2	-0.014	0.002	0	12	-10000	0	12
XPO1	-0.014	0	-10000	0	-10000	0	0
SFN	-0.013	0.003	0	33	-10000	0	33
MAP3K8	-0.013	0.004	-10000	0	-10000	0	0
NFAT4/CK1 alpha	-0.018	0.004	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.014	0.028	0.057	6	-0.093	3	9
CABIN1	-0.065	0.015	-10000	0	-10000	0	0
CALM1	-0.014	0.003	-10000	0	-10000	0	0
RAN	-0.014	0.001	0	3	-10000	0	3
MAP3K1	-0.014	0.001	0	1	-10000	0	1
CAMK4	-0.014	0	-10000	0	-10000	0	0
mol:Ca2+	-0.001	0	-10000	0	-10000	0	0
MAPK3	-0.014	0	-10000	0	-10000	0	0
YWHAH	-0.007	0.007	0	284	-10000	0	284
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.017	0	-10000	0	-10000	0	0
YWHAB	-0.014	0.001	0	2	-10000	0	2
MAPK8	-0.015	0	-10000	0	-10000	0	0
MAPK9	-0.014	0.001	0	3	-10000	0	3
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	-0.014	0.001	0	1	-10000	0	1
NFAT1-c-4/YWHAQ	-0.016	0.023	-10000	0	-0.15	3	3
PRKCH	-0.014	0.001	0	2	-10000	0	2
CABIN1/Cbp/p300	-0.018	0	-10000	0	-10000	0	0
CASP3	-0.012	0.006	-10000	0	-10000	0	0
PIM1	-0.014	0.001	0	2	-10000	0	2
Calcineurin A alpha-beta B1/FKBP12/FK506	-0.007	0	-10000	0	-10000	0	0
apoptosis	-0.01	0.001	0	7	-10000	0	7
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.002	0.006	0.042	7	-10000	0	7
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	-0.014	0	-10000	0	-10000	0	0
JNK2/NFAT4	-0.011	0.002	-10000	0	-10000	0	0
BAD/BCL-XL	-0.017	0	-10000	0	-10000	0	0
PRKCD	-0.014	0	-10000	0	-10000	0	0
NUP214	-0.014	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
PRKCA	-0.014	0	-10000	0	-10000	0	0
PRKCG	-0.014	0	-10000	0	-10000	0	0
PRKCQ	-0.014	0	-10000	0	-10000	0	0
FKBP38/BCL2	-0.017	0	-10000	0	-10000	0	0
EP300	-0.015	0	-10000	0	-10000	0	0
PRKCB1	-0.001	0.003	0	498	-10000	0	498
CSNK2A1	-0.014	0	-10000	0	-10000	0	0
NFATc/JNK1	-0.014	0.012	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	-0.013	0.003	-10000	0	-10000	0	0
FKBP12/FK506	-0.009	0	0	1	-10000	0	1
CSNK1A1	-0.014	0.003	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.013	0.003	-10000	0	-10000	0	0
NFATc/ERK1	-0.014	0.012	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.067	0.017	-10000	0	-10000	0	0
NR4A1	-0.025	0.014	-10000	0	-0.089	3	3
GSK3B	-0.014	0.001	-10000	0	-10000	0	0
positive T cell selection	-0.005	0.001	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.007	0.012	-10000	0	-10000	0	0
RCH1/ KPNB1	-0.017	0.003	0	12	-10000	0	12
YWHAQ	-0.014	0	-10000	0	-10000	0	0
PRKACA	-0.014	0	-10000	0	-10000	0	0
AKAP5	-0.014	0	-10000	0	-10000	0	0
MEF2D	-0.015	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	-0.014	0.002	0	6	-10000	0	6
NFATc/p38 alpha	-0.014	0.011	-10000	0	-10000	0	0
CREBBP	-0.015	0	-10000	0	-10000	0	0
BCL2	-0.014	0	-10000	0	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	-0.014	0.001	0	1	-10000	0	1
PTK2	-0.014	0.001	0	2	-10000	0	2
CRKL	-0.016	0.011	0.069	9	-10000	0	9
GRB2/SOS1/SHC	-0.012	0.004	0	51	-10000	0	51
HRAS	-0.014	0.001	0	2	-10000	0	2
IRS1/Crk	-0.017	0.002	0	9	-10000	0	9
IGF-1R heterotetramer/IGF1/PTP1B	-0.02	0.007	0.053	5	-10000	0	5
AKT1	-0.021	0.026	0.079	28	-10000	0	28
BAD	-0.023	0.027	0.07	28	-10000	0	28
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.016	0.011	0.069	9	-10000	0	9
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.017	0.009	0.076	5	-10000	0	5
RAF1	-0.011	0.026	0.12	2	-10000	0	2
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.015	0.009	0.079	5	-10000	0	5
YWHAZ	-0.014	0.002	0	6	-10000	0	6
IGF-1R heterotetramer/IGF1/IRS1	-0.012	0.009	0.083	5	-10000	0	5
PIK3CA	-0.014	0.003	0	25	-10000	0	25
RPS6KB1	-0.021	0.026	0.079	28	-10000	0	28
GNB2L1	-0.014	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.012	0.027	0.16	3	-10000	0	3
PXN	-0.014	0	-10000	0	-10000	0	0
PIK3R1	-0.013	0.004	0	36	-10000	0	36
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	-0.008	0.001	0	5	-10000	0	5
HRAS/GTP	-0.022	0.008	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.019	0.008	0.052	2	-10000	0	2
IGF-1R heterotetramer	-0.016	0.006	0.027	9	-10000	0	9
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.016	0.01	0.083	5	-10000	0	5
Crk/p130 Cas/Paxillin	-0.02	0.009	0.071	5	-10000	0	5
IGF1R	-0.016	0.006	0.027	9	-10000	0	9
IGF1	-0.016	0.005	0.032	5	-10000	0	5
IRS2/Crk	-0.02	0.01	0.074	5	-10000	0	5
PI3K	-0.019	0.01	0.083	3	-10000	0	3
apoptosis	0.024	0.028	-10000	0	-0.095	4	4
HRAS/GDP	-0.009	0.001	0	2	-10000	0	2
PRKCD	-0.007	0.014	-10000	0	-10000	0	0
RAF1/14-3-3 E	-0.013	0.027	0.11	2	-10000	0	2
BAD/14-3-3	-0.025	0.029	0.099	4	-10000	0	4
PRKCZ	-0.017	0.023	0.074	27	-10000	0	27
Crk/p130 Cas/Paxillin/FAK1	-0.031	0.024	0.048	27	-10000	0	27
PTPN1	-0.014	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.005	0.005	0.046	5	-10000	0	5
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.02	0.009	0.055	2	-10000	0	2
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.017	0.008	0.067	4	-10000	0	4
GRB10	-0.014	0.002	0	16	-10000	0	16
PTPN11	-0.016	0.011	0.069	9	-10000	0	9
IRS1	-0.012	0.007	0.069	4	-10000	0	4
IRS2	-0.016	0.011	0.069	9	-10000	0	9
IGF-1R heterotetramer/IGF1	-0.018	0.007	0.054	5	-10000	0	5
GRB2	-0.014	0.001	0	5	-10000	0	5
PDPK1	-0.018	0.024	0.08	27	-10000	0	27
YWHAE	-0.014	0.001	0	2	-10000	0	2
PRKD1	0.017	0.044	0.095	119	-10000	0	119
SHC1	-0.013	0.004	0	46	-10000	0	46

×

E-cadherin signaling events

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.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.02	0.004	0	19	-9999	19
E-cadherin/beta catenin	-0.017	0.002	0	8	-9999	8
CTNNB1	-0.014	0	-9999	0	-9999	0
JUP	-0.014	0.002	0	16	-9999	16
CDH1	-0.014	0.002	0	8	-9999	8

×

JNK signaling in the CD4+ TCR pathway

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.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.022	0.006	0	32	-9999	32
MAP4K1	-0.014	0.001	0	1	-9999	1
MAP3K8	-0.013	0.004	0	42	-9999	42
PRKCB	0	0	-10000	0	-9999	0
DBNL	0	0	-10000	0	-9999	0
CRKL	-0.014	0	-10000	0	-9999	0
MAP3K1	-0.013	0.007	0.059	3	-9999	3
JUN	-0.004	0.008	-10000	0	-9999	0
MAP3K7	-0.013	0.007	0.059	3	-9999	3
GRAP2	-0.014	0	-10000	0	-9999	0
CRK	-0.014	0	-10000	0	-9999	0
MAP2K4	-0.007	0.022	0.09	15	-9999	15
LAT	-0.014	0.001	0	1	-9999	1
LCP2	-0.013	0.003	0	30	-9999	30
MAPK8	0.001	0.007	-10000	0	-9999	0
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.008	0.004	0.05	2	-9999	2
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.021	0.005	0	32	-9999	32

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	-0.017	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	-0.023	0.003	0	6	-10000	0	6
CDKN1B	-0.009	0.012	-10000	0	-10000	0	0
CDKN1A	0.002	0.033	0.095	54	-10000	0	54
FRAP1	-0.014	0.001	0	1	-10000	0	1
PRKDC	-0.014	0.003	0	23	-10000	0	23
FOXO3	-0.009	0.012	-10000	0	-10000	0	0
AKT1	-0.006	0.001	-10000	0	-10000	0	0
BAD	-0.014	0	-10000	0	-10000	0	0
AKT3	-0.005	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	-0.009	0.012	-10000	0	-10000	0	0
AKT1/ASK1	-0.008	0.014	-10000	0	-10000	0	0
BAD/YWHAZ	-0.02	0.002	0	6	-10000	0	6
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	-0.014	0.001	0	1	-10000	0	1
JNK cascade	0.008	0.013	-10000	0	-10000	0	0
TSC1	-0.008	0.013	0.094	1	-10000	0	1
YWHAZ	-0.014	0.002	0	6	-10000	0	6
AKT1/RAF1	-0.008	0.014	-10000	0	-10000	0	0
EP300	-0.014	0	-10000	0	-10000	0	0
mol:GDP	-0.006	0.001	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	-0.009	0.012	-10000	0	-10000	0	0
YWHAQ	-0.014	0	-10000	0	-10000	0	0
TBC1D4	-0.011	0	-10000	0	-10000	0	0
MAP3K5	-0.014	0.001	0	4	-10000	0	4
MAPKAP1	-0.014	0	-10000	0	-10000	0	0
negative regulation of cell cycle	0.03	0.033	0.16	7	-10000	0	7
YWHAH	-0.007	0.007	0	284	-10000	0	284
AKT1S1	-0.003	0.012	-10000	0	-10000	0	0
CASP9	-0.008	0.016	0.13	3	-10000	0	3
YWHAB	-0.014	0.001	0	2	-10000	0	2
p27Kip1/KPNA1	-0.013	0.014	-10000	0	-10000	0	0
GBL	-0.014	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	-0.02	0	-10000	0	-10000	0	0
YWHAE	-0.014	0.001	0	2	-10000	0	2
SRC	-0.014	0	-10000	0	-10000	0	0
AKT2/p21CIP1	0	0.033	0.091	54	-10000	0	54
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.004	0.005	-10000	0	-10000	0	0
CHUK	-0.008	0.013	-10000	0	-10000	0	0
BAD/BCL-XL	-0.017	0.015	-10000	0	-10000	0	0
mTORC2	-0.018	0.001	0	1	-10000	0	1
AKT2	-0.005	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	-0.043	0.041	-10000	0	-0.19	7	7
PDPK1	-0.014	0	-10000	0	-10000	0	0
MDM2	-0.005	0.023	0.15	1	-10000	0	1
MAPKKK cascade	0.008	0.014	-10000	0	-10000	0	0
MDM2/Cbp/p300	-0.013	0.025	0.14	1	-10000	0	1
TSC1/TSC2	-0.013	0.012	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.013	0.024	0.14	1	-10000	0	1
glucose import	-0.015	0	-10000	0	-10000	0	0
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0	0.01	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.015	0	-10000	0	-10000	0	0
GSK3A	-0.009	0.012	-10000	0	-10000	0	0
FOXO1	-0.006	0.019	0.099	11	-10000	0	11
GSK3B	-0.009	0.012	-10000	0	-10000	0	0
SFN	-0.013	0.003	0	33	-10000	0	33
G1/S transition of mitotic cell cycle	-0.013	0.012	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	-0.003	0.01	-10000	0	-0.22	1	1
PRKACA	-0.014	0	-10000	0	-10000	0	0
KPNA1	-0.014	0	-10000	0	-10000	0	0
HSP90AA1	-0.014	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	-0.014	0	-10000	0	-10000	0	0
CREBBP	-0.014	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	-0.018	0.002	0	6	-9999	0	6
HDAC3	-0.014	0	-10000	0	-9999	0	0
Ran/GTP/Exportin 1/HDAC4	-0.019	0.002	0	4	-9999	0	4
GATA1/HDAC4	-0.017	0	-10000	0	-9999	0	0
GATA1/HDAC5	-0.017	0	-10000	0	-9999	0	0
GATA2/HDAC5	-0.017	0.001	0	1	-9999	0	1
HDAC5/BCL6/BCoR	-0.019	0.004	0	21	-9999	0	21
HDAC9	-0.014	0.001	0	2	-9999	0	2
Glucocorticoid receptor/Hsp90/HDAC6	-0.02	0	-10000	0	-9999	0	0
HDAC4/ANKRA2	-0.017	0.001	0	1	-9999	0	1
HDAC5/YWHAB	-0.017	0.001	0	2	-9999	0	2
NPC/RanGAP1/SUMO1/Ubc9	-0.005	0	0	1	-9999	0	1
GATA2	-0.014	0.001	0	1	-9999	0	1
HDAC4/RFXANK	-0.015	0.005	0	53	-9999	0	53
BCOR	-0.014	0.001	0	5	-9999	0	5
mol:GTP	0	0	-10000	0	-9999	0	0
HDAC10	0	0	-10000	0	-9999	0	0
HDAC5	-0.014	0	-10000	0	-9999	0	0
GNB1/GNG2	-0.008	0.001	0	6	-9999	0	6
Histones	-0.007	0.004	0.05	2	-9999	0	2
ADRBK1	-0.014	0	-10000	0	-9999	0	0
HDAC4	-0.014	0	-10000	0	-9999	0	0
XPO1	-0.014	0	-10000	0	-9999	0	0
HDAC5/ANKRA2	-0.017	0.001	0	1	-9999	0	1
HDAC4/Ubc9	-0.017	0	-10000	0	-9999	0	0
HDAC7	0	0	-10000	0	-9999	0	0
HDAC5/14-3-3 E	-0.017	0.001	0	2	-9999	0	2
TUBA1B	-0.014	0	-10000	0	-9999	0	0
HDAC6	-0.014	0	-10000	0	-9999	0	0
HDAC5/RFXANK	-0.015	0.005	0	53	-9999	0	53
CAMK4	-0.014	0	-10000	0	-9999	0	0
Tubulin/HDAC6	-0.019	0.005	0	34	-9999	0	34
SUMO1	-0.014	0	-10000	0	-9999	0	0
EntrezGene:9972	0	0	-10000	0	-9999	0	0
YWHAB	-0.014	0.001	0	2	-9999	0	2
GATA1	-0.014	0	-10000	0	-9999	0	0
EntrezGene:8021	0	0	-10000	0	-9999	0	0
YWHAE	-0.014	0.001	0	2	-9999	0	2
NR3C1	-0.014	0	-10000	0	-9999	0	0
SUMO1/HDAC4	-0.012	0.003	0.048	1	-9999	0	1
SRF	-0.014	0	-10000	0	-9999	0	0
HDAC4/YWHAB	-0.017	0.001	0	2	-9999	0	2
Tubulin	-0.016	0.004	0	34	-9999	0	34
HDAC4/14-3-3 E	-0.017	0.001	0	2	-9999	0	2
GNB1	-0.014	0.002	0	6	-9999	0	6
RANGAP1	-0.014	0	-10000	0	-9999	0	0
BCL6/BCoR	-0.016	0.003	0	21	-9999	0	21
HDAC4/HDAC3/SMRT (N-CoR2)	-0.02	0	-10000	0	-9999	0	0
HDAC4/SRF	-0.02	0	-10000	0	-9999	0	0
HDAC4/ER alpha	-0.017	0	-10000	0	-9999	0	0
EntrezGene:23225	0	0	-10000	0	-9999	0	0
positive regulation of chromatin silencing	-0.007	0.004	0.05	2	-9999	0	2
cell motility	-0.019	0.005	0	34	-9999	0	34
EntrezGene:23636	0	0	-10000	0	-9999	0	0
UBE2I	-0.014	0	-10000	0	-9999	0	0
HDAC7/HDAC3	-0.009	0	-10000	0	-9999	0	0
BCL6	-0.014	0.002	0	16	-9999	0	16
HDAC4/CaMK II delta B	-0.014	0	-10000	0	-9999	0	0
Hsp90/HDAC6	-0.017	0	-10000	0	-9999	0	0
ESR1	-0.014	0	-10000	0	-9999	0	0
HDAC6/HDAC11	-0.017	0	-10000	0	-9999	0	0
Ran/GTP/Exportin 1	-0.014	0.003	0.05	1	-9999	0	1
NPC	-0.005	0	0	1	-9999	0	1
MEF2C	-0.012	0.005	0	86	-9999	0	86
RAN	-0.014	0.001	0	3	-9999	0	3
HDAC4/MEF2C	-0.023	0.01	-10000	0	-9999	0	0
GNG2	0	0	-10000	0	-9999	0	0
NCOR2	-0.014	0	-10000	0	-9999	0	0
TUBB2A	-0.013	0.003	0	34	-9999	0	34
HDAC11	-0.014	0	-10000	0	-9999	0	0
HSP90AA1	-0.014	0	-10000	0	-9999	0	0
RANBP2	-0.014	0.001	0	1	-9999	0	1
ANKRA2	-0.014	0.001	0	1	-9999	0	1
RFXANK	-0.013	0.004	0	53	-9999	0	53
nuclear import	0.013	0.001	-10000	0	0	3	3

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.012	0.017	0.19	1	-10000	0	1
epithelial cell differentiation	-0.022	0.021	-10000	0	-10000	0	0
ITCH	-0.014	0.009	0.064	1	-10000	0	1
WWP1	-0.006	0.014	0.3	1	-10000	0	1
FYN	-0.014	0.003	0	21	-10000	0	21
EGFR	-0.009	0.007	0	194	-10000	0	194
PRL	-0.014	0.002	0	6	-10000	0	6
neuron projection morphogenesis	-0.024	0.031	0.12	1	-10000	0	1
PTPRZ1	-0.013	0.004	0	55	-10000	0	55
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.023	0.017	0.15	1	-10000	0	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.014	0.013	0.18	1	-10000	0	1
ADAM17	-0.014	0.009	0.064	1	-10000	0	1
ErbB4/ErbB4	-0.005	0.012	0.28	1	-10000	0	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.007	0.012	-10000	0	-10000	0	0
NCOR1	-0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.018	0.012	0.16	1	-10000	0	1
GRIN2B	-0.021	0.013	0.15	1	-10000	0	1
ErbB4/ErbB2/betacellulin	-0.018	0.013	0.16	1	-10000	0	1
STAT1	-0.014	0.003	0	18	-10000	0	18
HBEGF	-0.014	0.001	0	2	-10000	0	2
PRLR	-0.014	0	-10000	0	-10000	0	0
E4ICDs/ETO2	-0.012	0.017	0.19	1	-10000	0	1
axon guidance	-0.002	0.019	0.21	1	-10000	0	1
NEDD4	-0.013	0.009	0.064	1	-10000	0	1
Prolactin receptor/Prolactin receptor/Prolactin	-0.017	0.002	0	6	-10000	0	6
CBFA2T3	-0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB2/HBEGF	-0.018	0.013	0.16	1	-10000	0	1
MAPK3	-0.021	0.032	0.13	1	-10000	0	1
STAT1 (dimer)	-0.011	0.017	0.19	1	-10000	0	1
MAPK1	-0.02	0.032	0.13	1	-10000	0	1
JAK2	-0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.018	0.012	0.16	1	-10000	0	1
NRG1	-0.017	0.006	0.033	1	-10000	0	1
NRG3	0	0	-10000	0	-10000	0	0
NRG2	-0.014	0	-10000	0	-10000	0	0
NRG4	0	0	-10000	0	-10000	0	0
heart development	-0.002	0.019	0.21	1	-10000	0	1
neural crest cell migration	-0.018	0.012	0.16	1	-10000	0	1
ERBB2	-0.017	0.006	0.033	1	-10000	0	1
WWOX/E4ICDs	-0.012	0.017	0.19	1	-10000	0	1
SHC1	-0.013	0.004	0	46	-10000	0	46
ErbB4/EGFR/neuregulin 4	-0.007	0.013	-10000	0	-10000	0	0
apoptosis	0.008	0.014	-10000	0	-0.19	1	1
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.012	0.017	0.19	1	-10000	0	1
ErbB4/ErbB2/epiregulin	-0.018	0.012	0.16	1	-10000	0	1
ErbB4/ErbB4/betacellulin/betacellulin	-0.012	0.017	0.19	1	-10000	0	1
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.024	0.018	0.16	1	-10000	0	1
MDM2	-0.006	0.026	0.21	1	-10000	0	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.017	0.006	-10000	0	-10000	0	0
STAT5A	-0.007	0.019	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.012	0.013	-10000	0	-10000	0	0
DLG4	-0.014	0	-10000	0	-10000	0	0
GRB2/SHC	-0.015	0.005	0	51	-10000	0	51
E4ICDs/TAB2/NCoR1	-0.016	0.017	0.17	1	-10000	0	1
STAT5A (dimer)	-0.021	0.026	-10000	0	-10000	0	0
MAP3K7IP2	-0.014	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.006	0.023	-10000	0	-10000	0	0
LRIG1	-0.013	0.003	0	29	-10000	0	29
EREG	-0.014	0.002	0	10	-10000	0	10
BTC	-0.014	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.003	0.017	0.21	1	-10000	0	1
ERBB4	-0.005	0.012	0.28	1	-10000	0	1
STAT5B	-0.014	0	-10000	0	-10000	0	0
YAP1	0.007	0.016	-10000	0	-10000	0	0
GRB2	-0.014	0.001	0	5	-10000	0	5
ErbB4/ErbB2/neuregulin 4	-0.013	0.009	-10000	0	-10000	0	0
glial cell differentiation	0.016	0.017	-10000	0	-0.17	1	1
WWOX	-0.014	0	-10000	0	-10000	0	0
cell proliferation	-0.012	0.011	-10000	0	-10000	0	0

×

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

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
MET/RANBP9	-0.017	0.002	0	11	-10000	0	11
CRKL	-0.006	0.009	-10000	0	-10000	0	0
mol:PIP3	0.01	0.02	-10000	0	-0.32	2	2
AKT1	-0.003	0.019	0.11	4	-0.27	2	6
PTK2B	-0.014	0	-10000	0	-10000	0	0
RAPGEF1	-0.01	0.009	-10000	0	-10000	0	0
RANBP10	-0.014	0	-10000	0	-10000	0	0
PIK3CA	-0.014	0.003	0	25	-10000	0	25
HGF/MET/SHIP2	-0.02	0.003	0	12	-10000	0	12
MAP3K5	-0.01	0.008	-10000	0	-10000	0	0
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.017	0.003	0	12	-10000	0	12
AP1	-0.012	0.019	0.062	25	-10000	0	25
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	-0.013	0.004	0	46	-10000	0	46
apoptosis	0.011	0.045	-10000	0	-0.68	2	2
STAT3 (dimer)	-0.01	0.015	-10000	0	-0.095	9	9
GAB1/CRKL/SHP2/PI3K	-0.017	0.011	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	-0.01	0.01	-10000	0	-10000	0	0
PTPN11	-0.014	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	-0.014	0	-10000	0	-10000	0	0
PTEN	-0.014	0.001	0	2	-10000	0	2
ELK1	-0.002	0.044	0.22	17	-10000	0	17
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.005	0.002	-10000	0	-10000	0	0
PAK1	-0.008	0.018	-10000	0	-0.26	2	2
HGF/MET/RANBP10	-0.02	0.003	0	12	-10000	0	12
HRAS	-0.001	0.009	-10000	0	-10000	0	0
DOCK1	-0.01	0.009	-10000	0	-10000	0	0
GAB1	0	0.009	-10000	0	-10000	0	0
CRK	-0.006	0.009	-10000	0	-10000	0	0
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.004	0.008	-10000	0	-10000	0	0
JUN	-0.014	0.001	0	1	-10000	0	1
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.004	0.004	0.052	2	-10000	0	2
PIK3R1	-0.013	0.004	0	36	-10000	0	36
cell morphogenesis	-0.016	0.026	0.12	1	-10000	0	1
GRB2/SHC	-0.012	0.01	0.058	8	-10000	0	8
FOS	-0.011	0.006	0	127	-10000	0	127
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.002	0.044	0.22	17	-10000	0	17
HGF/MET/MUC20	-0.013	0.002	0	12	-10000	0	12
cell migration	-0.012	0.01	0.057	8	-10000	0	8
GRB2	-0.014	0.001	0	5	-10000	0	5
CBL	-0.014	0	-10000	0	-10000	0	0
MET/RANBP10	-0.017	0.002	0	10	-10000	0	10
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.011	0.002	-10000	0	-10000	0	0
MET/MUC20	-0.008	0.001	0	10	-10000	0	10
RAP1B	-0.01	0.008	-10000	0	-10000	0	0
RAP1A	-0.015	0.008	-10000	0	-10000	0	0
HGF/MET/RANBP9	-0.02	0.003	0	13	-10000	0	13
RAF1	-0.006	0.016	-10000	0	-0.31	1	1
STAT3	-0.008	0.009	0.051	12	-10000	0	12
cell proliferation	-0.008	0.031	0.11	9	-10000	0	9
RPS6KB1	0.002	0.005	-10000	0	-10000	0	0
MAPK3	-0.01	0.017	-10000	0	-10000	0	0
MAPK1	0.011	0.12	0.65	17	-10000	0	17
RANBP9	-0.014	0.001	0	1	-10000	0	1
MAPK8	-0.011	0.013	-10000	0	-10000	0	0
SRC	-0.014	0.01	0.049	12	-10000	0	12
PI3K	-0.012	0.01	0.058	8	-10000	0	8
MET/Glomulin	-0.007	0.001	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	-0.01	0.009	-10000	0	-10000	0	0
MET	-0.014	0.002	0	10	-10000	0	10
MAP4K1	-0.006	0.009	-10000	0	-10000	0	0
PTK2	-0.014	0.001	0	2	-10000	0	2
MAP2K2	-0.01	0.016	-10000	0	-0.3	1	1
BAD	-0.008	0.018	-10000	0	-0.26	2	2
MAP2K4	-0.013	0.01	-10000	0	-10000	0	0
SHP2/GRB2/SOS1/GAB1	-0.012	0.005	-10000	0	-10000	0	0
INPPL1	-0.014	0	-10000	0	-10000	0	0
PXN	-0.014	0	-10000	0	-10000	0	0
SH3KBP1	0	0	-10000	0	-10000	0	0
HGS	-0.009	0.004	0.043	2	-10000	0	2
PLCgamma1/PKC	-0.009	0	-10000	0	-10000	0	0
HGF	-0.014	0.001	0	2	-10000	0	2
RASA1	-0.014	0.002	0	8	-10000	0	8
NCK1	-0.014	0.002	0	11	-10000	0	11
PTPRJ	-0.014	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.014	0.011	0.057	12	-10000	0	12
PDPK1	0.002	0.018	-10000	0	-0.29	2	2
HGF/MET/SHIP	-0.013	0.002	0	12	-10000	0	12

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.006	0.001	-10000	0	-10000	0	0
Crk/p130 Cas/Paxillin	-0.025	0.01	-10000	0	-10000	0	0
JUN	-0.018	0.011	0.045	15	-10000	0	15
HRAS	-0.014	0.001	0	2	-10000	0	2
RET51/GFRalpha1/GDNF/GRB10	-0.023	0.004	0	19	-10000	0	19
RAP1A	-0.014	0	-10000	0	-10000	0	0
FRS2	-0.014	0.001	0	3	-10000	0	3
RAP1A/GDP	-0.009	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.024	0.002	0	3	-10000	0	3
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	-0.014	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.014	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.018	0.001	0	2	-10000	0	2
RHOA	-0.014	0.001	0	2	-10000	0	2
RAP1A/GTP	-0.026	0.002	-10000	0	-10000	0	0
GRB7	-0.014	0.001	0	1	-10000	0	1
RET51/GFRalpha1/GDNF	-0.024	0.002	0	3	-10000	0	3
MAPKKK cascade	-0.027	0.007	0.014	6	-10000	0	6
BCAR1	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.018	0.002	0	7	-10000	0	7
lamellipodium assembly	-0.016	0.015	0.038	1	-10000	0	1
RET51/GFRalpha1/GDNF/SHC	-0.022	0.007	0	47	-10000	0	47
PIK3CA	-0.014	0.003	0	25	-10000	0	25
RET9/GFRalpha1/GDNF/SHC	-0.016	0.005	0	46	-10000	0	46
RET9/GFRalpha1/GDNF/Shank3	-0.012	0.001	0	2	-10000	0	2
MAPK3	-0.029	0.008	0.078	3	-10000	0	3
DOK1	-0.014	0	-10000	0	-10000	0	0
DOK6	0	0	-10000	0	-10000	0	0
PXN	-0.014	0	-10000	0	-10000	0	0
neurite development	-0.027	0.009	0.069	3	-10000	0	3
DOK5	-0.013	0.004	0	36	-10000	0	36
GFRA1	-0.014	0.001	0	2	-10000	0	2
MAPK8	-0.014	0.01	0.049	14	-10000	0	14
HRAS/GTP	-0.025	0.007	0.02	8	-10000	0	8
tube development	-0.016	0.007	0.058	5	-10000	0	5
MAPK1	-0.028	0.01	0.078	3	-10000	0	3
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.009	0.001	-10000	0	-10000	0	0
Rac1/GDP	-0.009	0	-10000	0	-10000	0	0
SRC	-0.014	0	-10000	0	-10000	0	0
PDLIM7	-0.014	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.022	0.002	0	3	-10000	0	3
SHC1	-0.013	0.004	0	46	-10000	0	46
RET51/GFRalpha1/GDNF/Dok4	-0.024	0.002	0	3	-10000	0	3
RET51/GFRalpha1/GDNF/Dok5	-0.022	0.006	0	39	-10000	0	39
PRKCA	-0.014	0	-10000	0	-10000	0	0
HRAS/GDP	-0.009	0.001	0	2	-10000	0	2
CREB1	-0.003	0.001	-10000	0	-10000	0	0
PIK3R1	-0.013	0.004	0	36	-10000	0	36
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.008	0.003	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Grb7	-0.023	0.002	0	4	-10000	0	4
mol:GDP	0	0	-10000	0	-10000	0	0
RET	-0.014	0.001	0	1	-10000	0	1
DOK4	-0.014	0	-10000	0	-10000	0	0
JNK cascade	-0.018	0.011	0.084	1	-10000	0	1
RET9/GFRalpha1/GDNF/FRS2	-0.018	0.002	0	5	-10000	0	5
SHANK3	0	0	-10000	0	-10000	0	0
RASA1	-0.014	0.002	0	8	-10000	0	8
NCK1	-0.014	0.002	0	11	-10000	0	11
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.007	0.002	0	51	-10000	0	51
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.011	0.002	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.011	0.002	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.008	0.003	-10000	0	-10000	0	0
PI3K	-0.012	0.023	0.089	11	-10000	0	11
SOS1	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.016	0.002	0	7	-10000	0	7
GRB10	-0.014	0.002	0	16	-10000	0	16
activation of MAPKK activity	-0.011	0.009	0.05	1	-0.098	5	6
RET51/GFRalpha1/GDNF/FRS2	-0.023	0.003	0	6	-10000	0	6
GAB1	-0.014	0.001	0	4	-10000	0	4
IRS1	-0.014	0.001	0	5	-10000	0	5
IRS2	-0.014	0.002	0	11	-10000	0	11
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.01	0.003	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/PKC alpha	-0.024	0.002	0	3	-10000	0	3
GRB2	-0.014	0.001	0	5	-10000	0	5
PRKACA	-0.014	0	-10000	0	-10000	0	0
GDNF	-0.014	0	-10000	0	-10000	0	0
RAC1	-0.014	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.023	0.003	0	8	-10000	0	8
Rac1/GTP	-0.017	0.019	0.059	7	-10000	0	7
RET9/GFRalpha1/GDNF	-0.013	0.001	0	2	-10000	0	2
GFRalpha1/GDNF	-0.017	0.001	0	2	-10000	0	2

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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.Total.Perturbations
HIF3A	-0.014	0	-9999	0	-9999	0
oxygen homeostasis	0	0	-9999	0	-9999	0
TCEB2	-0.014	0	-9999	0	-9999	0
TCEB1	-0.014	0	-9999	0	-9999	0
HIF1A/p53	-0.009	0.013	-9999	0	-9999	0
HIF1A	-0.006	0.011	-9999	0	-9999	0
COPS5	-0.014	0	-9999	0	-9999	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.022	0	-9999	0	-9999	0
FIH (dimer)	-0.014	0	-9999	0	-9999	0
CDKN2A	-0.013	0.004	0	59	-9999	59
ARNT/IPAS	-0.017	0	-9999	0	-9999	0
HIF1AN	-0.014	0	-9999	0	-9999	0
GNB2L1	-0.014	0	-9999	0	-9999	0
HIF1A/ARNT	-0.01	0.014	-9999	0	-9999	0
CUL2	-0.014	0	-9999	0	-9999	0
OS9	-0.013	0.004	0	43	-9999	43
RACK1/Elongin B/Elongin C	-0.02	0	-9999	0	-9999	0
response to hypoxia	0	0	-9999	0	-9999	0
HIF1A/Hsp90	-0.01	0.014	-9999	0	-9999	0
PHD1-3/OS9	-0.021	0.007	0	48	-9999	48
HIF1A/RACK1/Elongin B/Elongin C	-0.017	0.018	-9999	0	-9999	0
VHL	0	0	-9999	0	-9999	0
HSP90AA1	-0.014	0	-9999	0	-9999	0
HIF1A/JAB1	-0.01	0.014	-9999	0	-9999	0
EGLN3	-0.014	0.001	0	4	-9999	4
EGLN2	-0.014	0	-9999	0	-9999	0
EGLN1	-0.014	0.001	0	1	-9999	1
TP53	-0.012	0.005	0	69	-9999	69
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	-0.002	0.004	-9999	0	-9999	0
ARNT	-0.014	0	-9999	0	-9999	0
ARD1A	-0.014	0.001	0	1	-9999	1
RBX1	-0.014	0	-9999	0	-9999	0
HIF1A/p19ARF	-0.01	0.012	-9999	0	-9999	0

×

Regulation of Androgen receptor activity

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
HDAC1	-0.008	0.003	0	65	-10000	0	65
SMARCC1	0.002	0.057	0.3	18	-10000	0	18
REL	-0.014	0	-10000	0	-10000	0	0
HDAC7	-0.03	0.027	0.11	7	-10000	0	7
JUN	-0.014	0.001	0	1	-10000	0	1
EP300	-0.014	0	-10000	0	-10000	0	0
KAT2B	0	0	-10000	0	-10000	0	0
KAT5	0	0	-10000	0	-10000	0	0
MAPK14	-0.018	0.007	0.019	9	-10000	0	9
FOXO1	-0.014	0.002	0	11	-10000	0	11
T-DHT/AR	-0.03	0.035	0.16	8	-10000	0	8
MAP2K6	-0.014	0.008	0.014	39	-10000	0	39
BRM/BAF57	-0.017	0	-10000	0	-10000	0	0
MAP2K4	-0.014	0.008	0.015	32	-10000	0	32
SMARCA2	-0.014	0	-10000	0	-10000	0	0
PDE9A	-0.01	0.03	0.31	4	-10000	0	4
NCOA2	-0.014	0	-10000	0	-10000	0	0
CEBPA	-0.014	0.002	0	16	-10000	0	16
EHMT2	-0.014	0	-10000	0	-10000	0	0
cell proliferation	-0.033	0.022	0.15	1	-10000	0	1
NR0B1	-0.013	0.004	0	49	-10000	0	49
EGR1	-0.014	0.003	-10000	0	-10000	0	0
RXRs/9cRA	-0.018	0.001	-10000	0	-10000	0	0
AR/RACK1/Src	-0.031	0.017	-10000	0	-10000	0	0
AR/GR	-0.018	0.014	0.066	1	-0.093	2	3
GNB2L1	-0.014	0	-10000	0	-10000	0	0
PKN1	-0.014	0.002	0	10	-10000	0	10
RCHY1	-0.014	0	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	-0.017	0.008	0.021	7	-10000	0	7
T-DHT/AR/TIF2/CARM1	-0.03	0.02	-10000	0	-10000	0	0
SRC	-0.028	0.013	0.078	2	-10000	0	2
NR3C1	-0.014	0	-10000	0	-10000	0	0
KLK3	-0.011	0.016	-10000	0	-10000	0	0
APPBP2	-0.014	0.008	0.014	39	-10000	0	39
TRIM24	-0.014	0.002	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.022	0.013	0.045	7	-10000	0	7
TMPRSS2	-0.011	0.024	0.28	3	-10000	0	3
RXRG	-0.014	0.001	0	3	-10000	0	3
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	-0.014	0	-10000	0	-10000	0	0
RXRB	-0.014	0	-10000	0	-10000	0	0
CARM1	-0.014	0	-10000	0	-10000	0	0
NR2C2	-0.014	0	-10000	0	-10000	0	0
KLK2	-0.03	0.014	-10000	0	-10000	0	0
AR	-0.014	0.013	0.058	10	-10000	0	10
SENP1	0	0	-10000	0	-10000	0	0
HSP90AA1	-0.014	0	-10000	0	-10000	0	0
MDM2	-0.013	0.003	-10000	0	-10000	0	0
SRY	-0.014	0.001	-10000	0	-10000	0	0
GATA2	-0.014	0.001	0	1	-10000	0	1
MYST2	-0.014	0	-10000	0	-10000	0	0
HOXB13	-0.015	0	-10000	0	-10000	0	0
T-DHT/AR/RACK1/Src	-0.031	0.017	-10000	0	-10000	0	0
positive regulation of transcription	-0.014	0.001	0	1	-10000	0	1
DNAJA1	-0.014	0.008	0.014	38	-10000	0	38
proteasomal ubiquitin-dependent protein catabolic process	-0.003	0.001	-10000	0	-10000	0	0
NCOA1	-0.01	0.02	0.097	18	-10000	0	18
SPDEF	-0.014	0	-10000	0	-10000	0	0
T-DHT/AR/TIF2	-0.017	0.012	-10000	0	-10000	0	0
T-DHT/AR/Hsp90	-0.026	0.017	0.076	2	-10000	0	2
GSK3B	-0.014	0.004	0.013	8	-10000	0	8
NR2C1	-0.014	0	-10000	0	-10000	0	0
mol:T-DHT	-0.025	0.012	-10000	0	-10000	0	0
SIRT1	-0.014	0	-10000	0	-10000	0	0
ZMIZ2	-0.014	0	-10000	0	-10000	0	0
POU2F1	-0.014	0.017	0.13	7	-10000	0	7
T-DHT/AR/DAX-1	-0.024	0.018	0.076	2	-10000	0	2
CREBBP	-0.014	0	-10000	0	-10000	0	0
SMARCE1	-0.014	0	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.025	0.096	0.37	7	-10000	0	7
PCK1	-0.01	0.068	0.4	5	-10000	0	5
HNF4A	-0.027	0.1	0.66	3	-10000	0	3
KCNJ11	-0.023	0.1	0.41	5	-10000	0	5
AKT1	-0.027	0.072	0.3	3	-10000	0	3
response to starvation	-0.002	0.001	-10000	0	-10000	0	0
DLK1	-0.013	0.13	0.44	13	-10000	0	13
NKX2-1	-0.011	0.064	0.34	1	-10000	0	1
ACADM	-0.025	0.096	0.36	8	-10000	0	8
TAT	-0.011	0.066	0.56	2	-10000	0	2
CEBPB	-0.014	0.007	0.06	4	-10000	0	4
CEBPA	-0.014	0.007	0.07	3	-10000	0	3
TTR	-0.011	0.067	0.6	3	-10000	0	3
PKLR	-0.025	0.095	0.37	6	-10000	0	6
APOA1	-0.012	0.11	0.74	3	-10000	0	3
CPT1C	-0.023	0.094	0.38	6	-10000	0	6
ALAS1	-0.009	0.075	0.43	2	-0.84	1	3
TFRC	-0.013	0.1	0.41	6	-0.73	3	9
FOXF1	-0.012	0.006	-10000	0	-0.12	1	1
NF1	-0.016	0.006	-10000	0	-0.16	1	1
HNF1A (dimer)	-0.018	0.006	0.13	1	-10000	0	1
CPT1A	-0.025	0.095	0.37	6	-10000	0	6
HMGCS1	-0.025	0.095	0.37	6	-10000	0	6
NR3C1	-0.014	0.02	0.11	13	-10000	0	13
CPT1B	-0.025	0.095	0.43	4	-10000	0	4
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	-0.016	0	-10000	0	-10000	0	0
GCK	-0.025	0.095	0.37	6	-10000	0	6
CREB1	-0.015	0.013	0.11	5	-10000	0	5
IGFBP1	-0.005	0.073	0.47	4	-10000	0	4
PDX1	-0.012	0.065	0.4	2	-10000	0	2
UCP2	-0.011	0.12	0.37	20	-10000	0	20
ALDOB	-0.026	0.11	0.41	5	-10000	0	5
AFP	-0.007	0.02	0.24	2	-0.081	3	5
BDH1	-0.026	0.098	0.37	6	-0.42	3	9
HADH	-0.025	0.11	0.4	6	-10000	0	6
F2	-0.012	0.11	0.89	2	-10000	0	2
HNF1A	-0.018	0.006	0.13	1	-10000	0	1
G6PC	-0.011	0.023	-10000	0	-10000	0	0
SLC2A2	-0.011	0.078	0.55	2	-10000	0	2
INS	-0.014	0.018	0.16	1	-0.12	13	14
FOXA1	-0.004	0.017	0.16	3	-0.11	3	6
FOXA3	-0.008	0.025	0.14	8	-0.14	3	11
FOXA2	-0.028	0.13	0.52	6	-10000	0	6
ABCC8	-0.026	0.11	0.41	5	-10000	0	5
ALB	-0.007	0.02	0.24	2	-0.081	3	5

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	-0.014	0	-10000	0	-10000	0	0
MKNK1	-0.014	0	-10000	0	-10000	0	0
mol:PIP3	-0.011	0.008	0.059	4	-10000	0	4
FRAP1	0.004	0.011	-10000	0	-10000	0	0
AKT1	-0.01	0.02	0.08	24	-10000	0	24
INSR	-0.014	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	-0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.015	0.024	0.073	26	-10000	0	26
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.017	0.008	-10000	0	-10000	0	0
TSC2	-0.014	0	-10000	0	-10000	0	0
RHEB/GDP	-0.022	0.013	0.04	2	-10000	0	2
TSC1	-0.014	0.002	0	8	-10000	0	8
Insulin Receptor/IRS1	0.006	0.005	0.059	5	-10000	0	5
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.014	0.013	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	-0.014	0	-10000	0	-10000	0	0
RPS6KB1	-0.001	0.017	0.12	1	-10000	0	1
MAP3K5	-0.003	0.012	-10000	0	-0.14	4	4
PIK3R1	-0.013	0.004	0	36	-10000	0	36
apoptosis	-0.003	0.012	-10000	0	-0.14	4	4
mol:LY294002	0	0	-10000	0	0	1	1
EIF4B	-0.005	0.016	0.11	1	-10000	0	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.007	0.019	0.11	1	-10000	0	1
eIF4E/eIF4G1/eIF4A1	-0.014	0.01	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.009	0.007	0.058	3	-10000	0	3
mTOR/RHEB/GTP/Raptor/GBL	-0.011	0.017	0.1	2	-10000	0	2
FKBP1A	-0.014	0.001	0	1	-10000	0	1
RHEB/GTP	-0.018	0.023	0.064	26	-10000	0	26
mol:Amino Acids	0	0	-10000	0	0	1	1
FKBP12/Rapamycin	-0.008	0.004	0.009	24	-10000	0	24
PDPK1	-0.012	0.021	0.081	24	-10000	0	24
EIF4E	-0.014	0.001	0	5	-10000	0	5
ASK1/PP5C	0.012	0.049	-10000	0	-0.55	4	4
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.001	0.006	-10000	0	-10000	0	0
TSC1/TSC2	-0.016	0.026	0.081	24	-10000	0	24
tumor necrosis factor receptor activity	0	0	0	1	-10000	0	1
RPS6	-0.014	0	-10000	0	-10000	0	0
PPP5C	-0.014	0	-10000	0	-10000	0	0
EIF4G1	-0.014	0.001	0	4	-10000	0	4
IRS1	0.001	0.006	0.063	5	-10000	0	5
INS	-0.014	0	-10000	0	-10000	0	0
PTEN	-0.014	0.001	0	2	-10000	0	2
PDK2	-0.012	0.021	0.081	24	-10000	0	24
EIF4EBP1	0.029	0.021	-10000	0	-10000	0	0
PIK3CA	-0.014	0.003	0	25	-10000	0	25
PPP2R5D	-0.001	0.011	-10000	0	-10000	0	0
peptide biosynthetic process	-0.018	0	-10000	0	-10000	0	0
RHEB	-0.014	0	-10000	0	-10000	0	0
EIF4A1	-0.014	0.002	0	10	-10000	0	10
mol:Rapamycin	0	0	0.002	2	-10000	0	2
EEF2	-0.018	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.027	0.015	-10000	0	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.015	0.004	-10000	0	-9999	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-9999	0
cytokine production during immune response	0.008	0.007	-10000	0	-9999	0
IL27/IL27R/JAK1	-0.028	0.008	-10000	0	-9999	0
TBX21	-0.039	0.019	-10000	0	-9999	0
IL12B	-0.014	0.002	0.029	1	-9999	1
IL12A	-0.009	0.001	0.01	1	-9999	1
IL6ST	-0.016	0.002	-10000	0	-9999	0
IL27RA/JAK1	-0.012	0.003	-10000	0	-9999	0
IL27	-0.002	0.001	-10000	0	-9999	0
TYK2	-0.015	0.003	0.049	1	-9999	1
T-helper cell lineage commitment	0.009	0.043	-10000	0	-9999	0
T-helper 2 cell differentiation	0.008	0.007	-10000	0	-9999	0
T cell proliferation during immune response	0.008	0.007	-10000	0	-9999	0
MAPKKK cascade	-0.008	0.007	-10000	0	-9999	0
STAT3	-0.014	0.002	0	10	-9999	10
STAT2	-0.014	0	-10000	0	-9999	0
STAT1	-0.015	0.003	-10000	0	-9999	0
IL12RB1	-0.014	0.001	0.018	1	-9999	1
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-9999	0
IL12RB2	-0.039	0.019	-10000	0	-9999	0
IL27/IL27R/JAK2/TYK2	-0.009	0.008	-10000	0	-9999	0
positive regulation of T cell mediated cytotoxicity	-0.008	0.007	-10000	0	-9999	0
STAT1 (dimer)	-0.043	0.014	-10000	0	-9999	0
JAK2	-0.015	0.002	0.04	1	-9999	1
JAK1	-0.015	0.002	-10000	0	-9999	0
STAT2 (dimer)	-0.013	0.008	-10000	0	-9999	0
T cell proliferation	-0.012	0.012	-10000	0	-9999	0
IL12/IL12R/TYK2/JAK2	0.004	0.008	-10000	0	-9999	0
IL17A	0.009	0.044	-10000	0	-9999	0
mast cell activation	0.008	0.007	-10000	0	-9999	0
IFNG	-0.001	0.005	0.1	1	-9999	1
T cell differentiation	-0.002	0.001	0.009	1	-9999	1
STAT3 (dimer)	-0.013	0.008	-10000	0	-9999	0
STAT5A (dimer)	-0.013	0.008	-10000	0	-9999	0
STAT4 (dimer)	-0.007	0.01	-10000	0	-9999	0
STAT4	-0.008	0.007	0	219	-9999	219
T cell activation	0.001	0	-10000	0	-9999	0
IL27R/JAK2/TYK2	-0.021	0.009	-10000	0	-9999	0
GATA3	0.001	0.022	-10000	0	-9999	0
IL18	-0.008	0.002	0	45	-9999	45
positive regulation of mast cell cytokine production	-0.013	0.008	-10000	0	-9999	0
IL27/EBI3	-0.011	0.003	-10000	0	-9999	0
IL27RA	-0.005	0.002	-10000	0	-9999	0
IL6	-0.014	0.005	-10000	0	-9999	0
STAT5A	-0.014	0.001	0	1	-9999	1
monocyte differentiation	0	0	0.005	1	-9999	1
IL2	0.001	0.002	-10000	0	-9999	0
IL1B	-0.008	0.001	0	14	-9999	14
EBI3	-0.016	0.002	-10000	0	-9999	0
TNF	-0.009	0.001	-0.001	3	-9999	3

×

Sumoylation by RanBP2 regulates transcriptional repression

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.Total.Perturbations
HDAC1	-0.012	0.005	0	65	-9999	65
Ran/GTP/Exportin 1/HDAC4	-0.022	0.002	-10000	0	-9999	0
MDM2/SUMO1	-0.011	0.003	0.048	1	-9999	1
HDAC4	-0.014	0	-10000	0	-9999	0
Ran/GTP/Exportin 1/HDAC1	-0.019	0.007	-10000	0	-9999	0
SUMO1	-0.014	0	-10000	0	-9999	0
NPC/RanGAP1/SUMO1	-0.004	0	-10000	0	-9999	0
mol:GTP	0	0	-10000	0	-9999	0
XPO1	-0.01	0	-10000	0	-9999	0
EntrezGene:23636	0	0	-10000	0	-9999	0
RAN	-0.014	0.001	0	3	-9999	3
EntrezGene:8021	0	0	-10000	0	-9999	0
RANBP2	-0.014	0.001	0	1	-9999	1
SUMO1/HDAC4	-0.012	0.003	0.048	1	-9999	1
SUMO1/HDAC1	-0.01	0.004	-10000	0	-9999	0
RANGAP1	-0.014	0	-10000	0	-9999	0
MDM2/SUMO1/SUMO1	-0.023	0.004	0	18	-9999	18
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	-0.005	0	0	1	-9999	1
Ran/GTP	-0.009	0.003	0.048	1	-9999	1
EntrezGene:23225	0	0	-10000	0	-9999	0
MDM2	-0.014	0.003	0	18	-9999	18
UBE2I	-0.014	0	-10000	0	-9999	0
Ran/GTP/Exportin 1	-0.014	0.003	-10000	0	-9999	0
NPC	-0.005	0	0	1	-9999	1
PIAS2	-0.014	0	-10000	0	-9999	0
PIAS1	-0.014	0	-10000	0	-9999	0
EntrezGene:9972	0	0	-10000	0	-9999	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	-0.014	0	-9999	0	-9999	0
ITGB7	-0.014	0.001	0	2	-9999	2
ITGA4	-0.014	0.001	0	5	-9999	5
alpha4/beta7 Integrin	-0.017	0.002	0	5	-9999	5
alpha4/beta1 Integrin	-0.017	0.002	0	5	-9999	5

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.026	0.003	-10000	0	-10000	0	0
TC10/GTP	-0.025	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	-0.025	0.003	-10000	0	-10000	0	0
HRAS	-0.014	0.001	0	2	-10000	0	2
APS homodimer	0	0	-10000	0	-10000	0	0
GRB14	-0.014	0.003	0	18	-10000	0	18
FOXO3	-0.002	0.008	-10000	0	-10000	0	0
AKT1	-0.024	0.034	0.12	5	-10000	0	5
INSR	-0.018	0.001	-10000	0	-10000	0	0
Insulin Receptor/Insulin	-0.026	0.003	0	8	-10000	0	8
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	-0.014	0.002	0	16	-10000	0	16
SORBS1	-0.014	0	-10000	0	-10000	0	0
CRK	-0.014	0	-10000	0	-10000	0	0
PTPN1	-0.026	0.003	-10000	0	-10000	0	0
CAV1	-0.009	0.011	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II/C3G	-0.022	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	-0.025	0.003	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.024	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.012	0.02	-10000	0	-0.21	5	5
RPS6KB1	-0.028	0.032	0.12	5	-10000	0	5
PARD6A	-0.014	0	-10000	0	-10000	0	0
CBL	-0.014	0	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.007	0.003	-10000	0	-10000	0	0
PIK3R1	-0.013	0.004	0	36	-10000	0	36
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.032	0.031	0.055	39	-10000	0	39
HRAS/GTP	-0.026	0.009	-10000	0	-10000	0	0
Insulin Receptor	-0.018	0.001	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.026	0.009	-10000	0	-10000	0	0
PRKCI	-0.006	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.03	0.012	-10000	0	-10000	0	0
SHC1	-0.013	0.004	0	46	-10000	0	46
negative regulation of MAPKKK cascade	0.014	0.008	-10000	0	-10000	0	0
PI3K	-0.024	0.009	-10000	0	-10000	0	0
NCK2	-0.014	0.001	0	1	-10000	0	1
RHOQ	-0.014	0	-10000	0	-10000	0	0
mol:H2O2	-0.004	0.001	0.004	8	-10000	0	8
HRAS/GDP	-0.009	0.001	0	2	-10000	0	2
AKT2	-0.025	0.034	0.12	5	-10000	0	5
PRKCZ	-0.008	0.005	-10000	0	-10000	0	0
SH2B2	0	0	-10000	0	-10000	0	0
SHC/SHIP	-0.019	0.009	0.085	2	-10000	0	2
F2RL2	-0.014	0	-10000	0	-10000	0	0
TRIP10	-0.014	0.002	0	6	-10000	0	6
Insulin Receptor/Insulin/Shc	-0.018	0.006	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	-0.013	0.001	0	6	-10000	0	6
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.021	0.007	-10000	0	-10000	0	0
RAPGEF1	-0.014	0	-10000	0	-10000	0	0
RASA1	-0.014	0.002	0	8	-10000	0	8
NCK1	-0.014	0.002	0	11	-10000	0	11
CBL/APS/CAP/Crk-II	-0.018	0	-10000	0	-10000	0	0
TC10/GDP	-0.009	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.023	0.008	-10000	0	-10000	0	0
INPP5D	-0.017	0.002	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
SGK1	-0.004	0.002	-10000	0	-10000	0	0
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	-0.014	0	-10000	0	-10000	0	0
IRS1	-0.014	0.001	0	5	-10000	0	5
p62DOK/RasGAP	0.014	0.008	-10000	0	-10000	0	0
INS	-0.018	0.001	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.017	0.002	-10000	0	-10000	0	0
GRB2	-0.014	0.001	0	5	-10000	0	5
EIF4EBP1	-0.014	0.026	0.13	2	-10000	0	2
PTPRA	-0.018	0.002	-10000	0	-10000	0	0
PIK3CA	-0.014	0.003	0	25	-10000	0	25
TC10/GTP/CIP4	-0.013	0.001	0	6	-10000	0	6
PDPK1	-0.014	0	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.01	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.019	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS3	-0.021	0.001	-10000	0	-10000	0	0
Par3/Par6	-0.022	0.002	0	6	-10000	0	6

×

LPA4-mediated signaling events

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.Total.Perturbations
ADCY4	-0.007	0	-9999	0	-9999	0
ADCY5	-0.007	0	-9999	0	-9999	0
ADCY6	-0.014	0	-9999	0	-9999	0
ADCY7	-0.013	0.001	0	5	-9999	5
ADCY1	-0.014	0	-9999	0	-9999	0
ADCY2	-0.014	0	-9999	0	-9999	0
ADCY3	-0.007	0	-9999	0	-9999	0
ADCY8	-0.013	0.002	0	7	-9999	7
PRKCE	-0.009	0	-9999	0	-9999	0
ADCY9	-0.014	0	-9999	0	-9999	0
mol:DAG	0	0	-9999	0	-9999	0
cAMP biosynthetic process	-0.014	0.008	-9999	0	-9999	0

×

Coregulation of Androgen receptor activity

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.Total.Perturbations
NRIP1	-0.014	0.001	-10000	0	-9999	0
SVIL	-0.014	0.003	-10000	0	-9999	0
ZNF318	-0.014	0	-10000	0	-9999	0
JMJD2C	-0.016	0	-10000	0	-9999	0
T-DHT/AR/Ubc9	-0.019	0.011	0.074	7	-9999	7
CARM1	-0.014	0	-10000	0	-9999	0
PRDX1	-0.014	0.001	-10000	0	-9999	0
PELP1	-0.014	0	-10000	0	-9999	0
CTNNB1	-0.014	0	-10000	0	-9999	0
AKT1	-0.014	0.001	-10000	0	-9999	0
PTK2B	-0.014	0	-10000	0	-9999	0
MED1	-0.014	0	-10000	0	-9999	0
MAK	-0.013	0.002	-10000	0	-9999	0
response to oxidative stress	0	0	-10000	0	-9999	0
HIP1	-0.013	0.004	-10000	0	-9999	0
GSN	-0.014	0.002	-10000	0	-9999	0
NCOA2	-0.014	0	-10000	0	-9999	0
NCOA6	-0.014	0.001	-10000	0	-9999	0
DNA-PK	-0.019	0.004	-10000	0	-9999	0
NCOA4	-0.014	0.001	0	1	-9999	1
PIAS3	-0.014	0.001	-10000	0	-9999	0
cell proliferation	-0.006	0.003	-10000	0	-9999	0
XRCC5	-0.014	0	-10000	0	-9999	0
UBE3A	-0.015	0	-10000	0	-9999	0
T-DHT/AR/SNURF	-0.013	0.009	0.07	6	-9999	6
FHL2	-0.014	0.007	0.049	3	-9999	3
RANBP9	-0.014	0.001	-10000	0	-9999	0
JMJD1A	-0.017	0.011	0.12	3	-9999	3
CDK6	-0.014	0	-10000	0	-9999	0
TGFB1I1	-0.002	0.005	-10000	0	-9999	0
T-DHT/AR/CyclinD1	-0.016	0.01	0.075	2	-9999	2
XRCC6	-0.014	0	-10000	0	-9999	0
T-DHT/AR	-0.024	0.02	0.15	6	-9999	6
CTDSP1	-0.014	0.001	-10000	0	-9999	0
CTDSP2	-0.013	0.004	-10000	0	-9999	0
BRCA1	-0.014	0.001	-10000	0	-9999	0
TCF4	-0.014	0.002	-10000	0	-9999	0
CDKN2A	-0.012	0.004	-10000	0	-9999	0
SRF	-0.014	0.012	0.12	4	-9999	4
NKX3-1	-0.016	0.014	0.089	6	-9999	6
KLK3	0.003	0.017	-10000	0	-9999	0
TMF1	-0.014	0.001	0	4	-9999	4
HNRNPA1	-0.014	0	-10000	0	-9999	0
AOF2	-0.014	0.002	-10000	0	-9999	0
APPL1	-0.017	0.001	-10000	0	-9999	0
T-DHT/AR/Caspase 8	-0.019	0.01	0.074	5	-9999	5
AR	-0.019	0.008	0.044	7	-9999	7
UBA3	0	0	-10000	0	-9999	0
PATZ1	-0.014	0	-10000	0	-9999	0
PAWR	-0.014	0	-10000	0	-9999	0
PRKDC	-0.013	0.003	-10000	0	-9999	0
PA2G4	-0.014	0.001	-10000	0	-9999	0
UBE2I	-0.014	0	-10000	0	-9999	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.017	0.011	0.071	7	-9999	7
RPS6KA3	-0.014	0.001	-10000	0	-9999	0
T-DHT/AR/ARA70	-0.019	0.011	0.074	7	-9999	7
LATS2	0	0	-10000	0	-9999	0
T-DHT/AR/PRX1	-0.017	0.011	0.071	7	-9999	7
Cyclin D3/CDK11 p58	-0.008	0	-10000	0	-9999	0
VAV3	-0.013	0.004	-10000	0	-9999	0
KLK2	-0.015	0.009	0.049	6	-9999	6
CASP8	-0.014	0.002	-10000	0	-9999	0
T-DHT/AR/TIF2/CARM1	-0.023	0.012	0.075	7	-9999	7
TMPRSS2	-0.017	0.008	0.047	3	-9999	3
CCND1	-0.012	0.006	-10000	0	-9999	0
PIAS1	-0.015	0	-10000	0	-9999	0
mol:T-DHT	-0.006	0.005	0.035	7	-9999	7
CDC2L1	0	0	-10000	0	-9999	0
PIAS4	-0.015	0	-10000	0	-9999	0
T-DHT/AR/CDK6	-0.019	0.011	0.074	7	-9999	7
CMTM2	0	0	-10000	0	-9999	0
SNURF	0	0	-10000	0	-9999	0
ZMIZ1	-0.019	0.008	0.044	6	-9999	6
CCND3	-0.014	0.001	0	1	-9999	1
TGIF1	-0.004	0.006	-10000	0	-9999	0
FKBP4	-0.014	0	-10000	0	-9999	0

×

Rapid glucocorticoid signaling

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.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.011	0.001	0	6	-9999	6
MAPK9	-0.003	0	0	3	-9999	3
adrenocorticotropin secretion	-0.009	0	0	1	-9999	1
GNB1/GNG2	-0.007	0.001	0	6	-9999	6
GNB1	-0.014	0.002	0	6	-9999	6
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	0	-9999	0
mol:GDP	0	0	-9999	0	-9999	0
MAPK14	-0.003	0	0	2	-9999	2
Gs family/GTP	-0.006	0	-9999	0	-9999	0
EntrezGene:2778	0	0	-9999	0	-9999	0
vasopressin secretion	0	0	-9999	0	-9999	0
G-protein coupled receptor activity	0	0	-9999	0	-9999	0
ChemicalAbstracts:86-01-1	0	0	-9999	0	-9999	0
glutamate secretion	0.002	0	-9999	0	-9999	0
GNAL	-0.014	0	-9999	0	-9999	0
GNG2	0	0	-9999	0	-9999	0
CRH	-0.014	0.001	0	1	-9999	1
mol:cortisol	0	0	-9999	0	-9999	0
MAPK8	-0.003	0	-9999	0	-9999	0
MAPK11	-0.003	0	-9999	0	-9999	0

×

Visual signal transduction: Rods

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.Total.Perturbations
mol:K +	-0.014	0	-9999	0	-9999	0
GNAT1/GTP	-0.009	0	-9999	0	-9999	0
Metarhodopsin II/Arrestin	-0.013	0.001	0	1	-9999	1
PDE6G/GNAT1/GTP	-0.014	0	-9999	0	-9999	0
mol:GTP	0	0	-9999	0	-9999	0
absorption of light	0	0	-9999	0	-9999	0
GNAT1	-0.014	0	-9999	0	-9999	0
GRK1	0	0	-9999	0	-9999	0
CNG Channel	-0.03	0	-9999	0	-9999	0
mol:Na +	-0.024	0	-9999	0	-9999	0
mol:ADP	0	0	-9999	0	-9999	0
RGS9-1/Gbeta5/R9AP	-0.013	0.002	0	7	-9999	7
mol:GDP	0	0	-9999	0	-9999	0
cGMP/CNG Channel	-0.025	0	-9999	0	-9999	0
CNGB1	-0.014	0	-9999	0	-9999	0
RDH5	-0.014	0.001	0	1	-9999	1
SAG	-0.014	0.001	0	1	-9999	1
mol:Ca2+	-0.029	0	-9999	0	-9999	0
Na + (4 Units)	-0.028	0	-9999	0	-9999	0
RGS9	-0.014	0	-9999	0	-9999	0
GNB1/GNGT1	-0.017	0.002	0	6	-9999	6
GNAT1/GDP	-0.016	0.002	0	7	-9999	7
GUCY2D	-0.014	0	-9999	0	-9999	0
GNGT1	-0.014	0	-9999	0	-9999	0
GUCY2F	-0.014	0	-9999	0	-9999	0
GNB5	-0.014	0.002	0	7	-9999	7
mol:GMP (4 units)	-0.022	0	-9999	0	-9999	0
mol:11-cis-retinal	-0.014	0.001	0	1	-9999	1
mol:cGMP	-0.016	0	-9999	0	-9999	0
GNB1	-0.014	0.002	0	6	-9999	6
Rhodopsin	-0.017	0.001	0	1	-9999	1
SLC24A1	-0.014	0	-9999	0	-9999	0
CNGA1	-0.014	0	-9999	0	-9999	0
Metarhodopsin II	-0.006	0	-9999	0	-9999	0
mol:Ca ++	0	0	-9999	0	-9999	0
GC1/GCAP Family	-0.012	0	-9999	0	-9999	0
RGS9BP	0	0	-9999	0	-9999	0
Metarhodopsin II/Transducin	-0.007	0.001	0	6	-9999	6
GCAP Family/Ca ++	-0.006	0	-9999	0	-9999	0
PDE6A/B	-0.017	0	-9999	0	-9999	0
mol:Pi	-0.013	0.002	0	7	-9999	7
mol:all-trans-retinal	0	0	-9999	0	-9999	0
Transducin	-0.018	0.002	0	6	-9999	6
PDE6B	-0.014	0	-9999	0	-9999	0
PDE6A	-0.014	0	-9999	0	-9999	0
PDE6G	-0.014	0	-9999	0	-9999	0
RHO	-0.014	0	-9999	0	-9999	0
PDE6	-0.026	0.003	-9999	0	-9999	0
GUCA1A	0	0	-9999	0	-9999	0
GC2/GCAP Family	-0.012	0	-9999	0	-9999	0
GUCA1C	0	0	-9999	0	-9999	0
GUCA1B	-0.014	0	-9999	0	-9999	0

×

Arf1 pathway

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

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

Entity	Mean	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	-0.008	0.003	0.043	2	-10000	0	2
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	-0.001	0.008	-10000	0	-0.12	2	2
AP2	-0.008	0.001	0	11	-10000	0	11
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	-0.015	0	-10000	0	-10000	0	0
CLTB	-0.014	0.001	0	2	-10000	0	2
coatomer protein complex/ARF1/GTP/ER cargo protein	-0.008	0.001	-10000	0	-10000	0	0
CD4	-0.014	0.003	0	20	-10000	0	20
CLTA	-0.014	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0	-10000	0	-10000	0	0
ARFGAP1	-0.009	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.004	0	-10000	0	-10000	0	0
ARF1/GTP	-0.011	0.001	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.01	0.001	-10000	0	-10000	0	0
mol:Choline	-0.005	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	-0.015	0.002	0.012	1	-10000	0	1
DDEF1	-0.004	0	-10000	0	-10000	0	0
ARF1/GDP	-0.003	0.001	-10000	0	-10000	0	0
AP2M1	-0.014	0.002	0	11	-10000	0	11
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.013	0.001	0.004	1	-10000	0	1
Rac/GTP	-0.01	0.001	0.008	1	-10000	0	1
ARF1/GTP/GGA3/ARF-GAP1	-0.017	0.002	0.01	1	-10000	0	1
ARFIP2	-0.015	0	-10000	0	-10000	0	0
COPA	-0.014	0	-10000	0	-10000	0	0
RAC1	-0.014	0	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	-0.004	0.001	-10000	0	-10000	0	0
ARF1/GTP/ARHGAP10	-0.008	0.001	-10000	0	-10000	0	0
GGA3	-0.014	0	-10000	0	-10000	0	0
ARF1/GTP/Membrin	-0.006	0	-10000	0	-10000	0	0
AP2A1	0	0	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	-0.007	0.001	-10000	0	-10000	0	0
ARF1/GDP/Membrin	0.006	0.001	-10000	0	-10000	0	0
Arfaptin 2/Rac/GDP	-0.014	0	-10000	0	-10000	0	0
CYTH2	-0.002	0	-10000	0	-10000	0	0
ARF1/GTP/GGA3	-0.015	0.001	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	-0.009	0	-10000	0	-10000	0	0
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	-0.006	0.002	-10000	0	-10000	0	0
PLD2	-0.005	0	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	-0.009	0	-10000	0	-10000	0	0
PIP5K1A	-0.004	0	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	-0.009	0.001	-10000	0	-10000	0	0
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.005	0	-10000	0	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	-0.009	0	-10000	0	-10000	0	0
GOSR2	0.001	0	-10000	0	-10000	0	0
USO1	0.001	0	-10000	0	-10000	0	0
GBF1	0.001	0	-10000	0	-10000	0	0
ARF1/GTP/Arfaptin 2	-0.016	0.001	0.005	1	-10000	0	1
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.013	0.003	0	31	-10000	0	31

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.017	0.001	0	3	-9999	3
FBXW11	-0.014	0	-9999	0	-9999	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	0	-9999	0
beta TrCP1/SCF ubiquitin ligase complex	-0.014	0	-9999	0	-9999	0
CHUK	-0.014	0.001	0	1	-9999	1
NF kappa B2 p100/RelB	-0.027	0.002	-9999	0	-9999	0
NFKB1	-0.014	0.001	0	4	-9999	4
MAP3K14	-0.014	0.001	0	2	-9999	2
NF kappa B1 p50/RelB	-0.017	0.002	0	5	-9999	5
RELB	-0.014	0.001	0	1	-9999	1
NFKB2	-0.014	0	-9999	0	-9999	0
NF kappa B2 p52/RelB	-0.013	0.001	0	1	-9999	1
regulation of B cell activation	-0.013	0.001	0	1	-9999	1

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
MAPKKK cascade	-0.013	0	-9999	-9999
EFNA5	-0.014	0	-9999	-9999
FYN	-0.017	0.003	-9999	-9999
neuron projection morphogenesis	-0.013	0	-9999	-9999
cell-cell signaling	0	0	-9999	-9999
Ephrin A5/EPHA5	-0.014	0	-9999	-9999
EPHA5	-0.014	0	-9999	-9999

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
cAMP biosynthetic process	0.014	-9999	-9999
PI3K Class IB/PDE3B	-0.014	-9999	-9999
PDE3B	-0.014	-9999	-9999

pid_entity	TCGA.87.5896	TCGA.81.5910	TCGA.76.6285	TCGA.76.6282
109_MAP3K5	0.01	-0.011	-0.011	-0.011
47_PPARGC1A	-0.014	-0.014	-0.014	-0.014
105_BMP4	-0.014	-0.014	-0.014	-0.014
105_BMP6	-0.014	-0.014	-0.014	-0.014
105_BMP7	-0.014	-0.014	-0.014	-0.014
105_BMP2	-0.014	-0.014	0	-0.014
131_RELN/VLDLR	-0.024	0	-0.024	0
30_TGFB1/TGF beta receptor Type II	0	-0.014	-0.022	0
84_STAT5B	0.096	0.06	-0.004	0.06
84_STAT5A	0.096	0.06	-0.004	0.06