PARADIGM pathway analysis of mRNASeq expression and copy number data - Bladder Urothelial Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Signaling events regulated by Ret tyrosine kinase	90
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	88
Signaling mediated by p38-alpha and p38-beta	82
Endothelins	80
IGF1 pathway	80
Nongenotropic Androgen signaling	74
Signaling events mediated by the Hedgehog family	68
IL4-mediated signaling events	66
Reelin signaling pathway	65
Aurora B signaling	62

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
Signaling events regulated by Ret tyrosine kinase	0.2206	90	7435	82	-0.24	0.031	1000	-1000	-0.041	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.2157	88	6014	68	-0.68	0.35	1000	-1000	-0.042	-1000
Signaling mediated by p38-alpha and p38-beta	0.2010	82	3618	44	-0.23	0.027	1000	-1000	-0.021	-1000
Endothelins	0.1961	80	7767	96	-0.38	0.089	1000	-1000	-0.037	-1000
IGF1 pathway	0.1961	80	4589	57	-0.2	0.05	1000	-1000	-0.024	-1000
Nongenotropic Androgen signaling	0.1814	74	3861	52	-0.26	0.15	1000	-1000	-0.017	-1000
Signaling events mediated by the Hedgehog family	0.1667	68	3579	52	-0.14	0.14	1000	-1000	-0.019	-1000
IL4-mediated signaling events	0.1618	66	6095	91	-0.71	0.51	1000	-1000	-0.045	-1000
Reelin signaling pathway	0.1593	65	3648	56	-0.15	0.062	1000	-1000	-0.027	-1000
Aurora B signaling	0.1520	62	4156	67	-0.32	0.24	1000	-1000	-0.022	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.1495	61	4799	78	-0.28	0.1	1000	-1000	-0.041	-1000
Thromboxane A2 receptor signaling	0.1446	59	6224	105	-0.22	0.049	1000	-1000	-0.032	-1000
p75(NTR)-mediated signaling	0.1348	55	6876	125	-0.11	0.078	1000	-1000	-0.039	-1000
Fc-epsilon receptor I signaling in mast cells	0.1225	50	4861	97	-0.13	0.029	1000	-1000	-0.042	-1000
Glypican 2 network	0.1225	50	200	4	0.037	0.093	1000	-1000	0.013	-1000
TCGA08_retinoblastoma	0.1225	50	402	8	-0.025	0.11	1000	-1000	-0.001	-1000
Plasma membrane estrogen receptor signaling	0.1225	50	4353	86	-0.27	0.15	1000	-1000	-0.035	-1000
Ephrin A reverse signaling	0.1152	47	332	7	-0.057	0.011	1000	-1000	-0.002	-1000
TCR signaling in naïve CD8+ T cells	0.1152	47	4448	93	-0.12	0.05	1000	-1000	-0.032	-1000
S1P4 pathway	0.1127	46	1162	25	-0.12	0.046	1000	-1000	-0.013	-1000
Ras signaling in the CD4+ TCR pathway	0.1127	46	790	17	-0.12	0.037	1000	-1000	-0.009	-1000
LPA receptor mediated events	0.1103	45	4610	102	-0.24	0.068	1000	-1000	-0.064	-1000
IL23-mediated signaling events	0.1103	45	2748	60	-0.47	0.037	1000	-1000	-0.021	-1000
S1P5 pathway	0.1078	44	761	17	-0.12	0.078	1000	-1000	-0.005	-1000
Integrins in angiogenesis	0.1078	44	3745	84	-0.23	0.1	1000	-1000	-0.03	-1000
Calcium signaling in the CD4+ TCR pathway	0.1029	42	1310	31	-0.2	0.026	1000	-1000	-0.03	-1000
S1P1 pathway	0.1005	41	1508	36	-0.3	0.026	1000	-1000	-0.018	-1000
Rapid glucocorticoid signaling	0.0980	40	801	20	-0.17	0.059	1000	-1000	-0.002	-1000
BMP receptor signaling	0.0956	39	3234	81	-0.26	0.071	1000	-1000	-0.027	-1000
IL6-mediated signaling events	0.0956	39	2976	75	-0.2	0.062	1000	-1000	-0.031	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0931	38	1977	52	-0.25	0.038	1000	-1000	-0.024	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0931	38	4617	120	-0.24	0.17	1000	-1000	-0.033	-1000
PDGFR-alpha signaling pathway	0.0907	37	1670	44	-0.3	0.039	1000	-1000	-0.031	-1000
amb2 Integrin signaling	0.0907	37	3090	82	-0.29	0.068	1000	-1000	-0.021	-1000
JNK signaling in the CD4+ TCR pathway	0.0882	36	612	17	-0.17	0.03	1000	-1000	-0.027	-1000
Glypican 1 network	0.0882	36	1731	48	-0.19	0.048	1000	-1000	-0.015	-1000
S1P3 pathway	0.0882	36	1532	42	-0.12	0.041	1000	-1000	-0.018	-1000
IL12-mediated signaling events	0.0858	35	3096	87	-0.4	0.057	1000	-1000	-0.057	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0833	34	1840	54	-0.15	0.062	1000	-1000	-0.023	-1000
PLK1 signaling events	0.0833	34	2904	85	-0.028	0.16	1000	-1000	-0.027	-1000
Glucocorticoid receptor regulatory network	0.0833	34	3978	114	-0.52	0.16	1000	-1000	-0.047	-1000
LPA4-mediated signaling events	0.0784	32	391	12	-0.13	0.008	1000	-1000	-0.02	-1000
HIF-1-alpha transcription factor network	0.0784	32	2457	76	-0.12	0.069	1000	-1000	-0.039	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0784	32	2875	88	-0.17	0.051	1000	-1000	-0.05	-1000
Coregulation of Androgen receptor activity	0.0760	31	2392	76	-0.18	0.11	1000	-1000	-0.015	-1000
Syndecan-1-mediated signaling events	0.0760	31	1059	34	-0.076	0.13	1000	-1000	-0.022	-1000
BCR signaling pathway	0.0735	30	3058	99	-0.1	0.037	1000	-1000	-0.042	-1000
Osteopontin-mediated events	0.0711	29	1128	38	-0.12	0.1	1000	-1000	-0.026	-1000
Syndecan-2-mediated signaling events	0.0711	29	2043	69	-0.041	0.056	1000	-1000	-0.027	-1000
Arf6 signaling events	0.0711	29	1804	62	-0.17	0.059	1000	-1000	-0.031	-1000
Aurora C signaling	0.0686	28	198	7	0	0.11	1000	-1000	-0.01	-1000
Wnt signaling	0.0662	27	195	7	-0.01	0.03	1000	-1000	-0.006	-1000
FOXM1 transcription factor network	0.0662	27	1404	51	-0.18	0.11	1000	-1000	-0.055	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0637	26	886	34	-0.022	0.039	1000	-1000	-0.024	-1000
ErbB2/ErbB3 signaling events	0.0613	25	1687	65	-0.18	0.039	1000	-1000	-0.039	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0613	25	2145	85	-0.23	0.039	1000	-1000	-0.045	-1000
FAS signaling pathway (CD95)	0.0613	25	1177	47	-0.53	0.044	1000	-1000	-0.024	-1000
Visual signal transduction: Cones	0.0588	24	937	38	-0.077	0.078	1000	-1000	-0.006	-1000
Presenilin action in Notch and Wnt signaling	0.0564	23	1409	61	-0.12	0.11	1000	-1000	-0.045	-1000
Noncanonical Wnt signaling pathway	0.0539	22	586	26	-0.072	0.03	1000	-1000	-0.03	-1000
Class IB PI3K non-lipid kinase events	0.0515	21	63	3	0	-1000	1000	-1000	-0.014	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0490	20	671	33	-0.22	0.11	1000	-1000	-0.023	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0466	19	549	28	-0.12	0.059	1000	-1000	-0.011	-1000
Aurora A signaling	0.0466	19	1174	60	-0.21	0.16	1000	-1000	-0.013	-1000
Canonical Wnt signaling pathway	0.0466	19	1004	51	-0.082	0.11	1000	-1000	-0.038	-1000
Syndecan-4-mediated signaling events	0.0466	19	1332	67	-0.13	0.067	1000	-1000	-0.027	-1000
Visual signal transduction: Rods	0.0466	19	1035	52	-0.077	0.1	1000	-1000	-0.012	-1000
Regulation of Androgen receptor activity	0.0466	19	1370	70	-0.18	0.036	1000	-1000	-0.03	-1000
Hedgehog signaling events mediated by Gli proteins	0.0441	18	1180	65	-0.12	0.065	1000	-1000	-0.029	-1000
Effects of Botulinum toxin	0.0441	18	481	26	-0.01	0.056	1000	-1000	-0.001	-1000
Cellular roles of Anthrax toxin	0.0417	17	673	39	-0.075	0.036	1000	-1000	-0.015	-1000
Ceramide signaling pathway	0.0417	17	1293	76	-0.19	0.071	1000	-1000	-0.022	-1000
ceramide signaling pathway	0.0417	17	843	49	0	0.05	1000	-1000	-0.04	-1000
TCGA08_p53	0.0417	17	125	7	-0.004	0.027	1000	-1000	-0.003	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0417	17	1273	74	-0.19	0.064	1000	-1000	-0.054	-1000
Ephrin B reverse signaling	0.0392	16	799	48	-0.038	0.041	1000	-1000	-0.024	-1000
Insulin Pathway	0.0392	16	1208	74	-0.19	0.066	1000	-1000	-0.032	-1000
Signaling events mediated by PTP1B	0.0368	15	1149	76	-0.11	0.042	1000	-1000	-0.031	-1000
Nectin adhesion pathway	0.0368	15	1000	63	-0.034	0.056	1000	-1000	-0.036	-1000
EPHB forward signaling	0.0343	14	1233	85	-0.013	0.069	1000	-1000	-0.044	-1000
Caspase cascade in apoptosis	0.0319	13	964	74	-0.049	0.05	1000	-1000	-0.03	-1000
ErbB4 signaling events	0.0319	13	902	69	-0.18	0.047	1000	-1000	-0.03	-1000
IL2 signaling events mediated by PI3K	0.0319	13	775	58	-0.063	0.12	1000	-1000	-0.031	-1000
Regulation of p38-alpha and p38-beta	0.0319	13	713	54	-0.1	0.06	1000	-1000	-0.04	-1000
IL27-mediated signaling events	0.0319	13	709	51	-0.18	0.047	1000	-1000	-0.048	-1000
IL2 signaling events mediated by STAT5	0.0319	13	296	22	-0.037	0.076	1000	-1000	-0.019	-1000
EGFR-dependent Endothelin signaling events	0.0319	13	273	21	-0.037	0.074	1000	-1000	-0.032	-1000
PDGFR-beta signaling pathway	0.0319	13	1310	97	-0.078	0.058	1000	-1000	-0.036	-1000
Regulation of nuclear SMAD2/3 signaling	0.0294	12	1761	136	-0.15	0.092	1000	-1000	-0.029	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0294	12	1005	83	-0.25	0.044	1000	-1000	-0.025	-1000
Class I PI3K signaling events mediated by Akt	0.0270	11	758	68	-0.14	0.064	1000	-1000	-0.022	-1000
FOXA2 and FOXA3 transcription factor networks	0.0245	10	479	46	-0.14	0.18	1000	-1000	-0.037	-1000
IFN-gamma pathway	0.0245	10	703	68	-0.12	0.081	1000	-1000	-0.034	-1000
Signaling events mediated by HDAC Class III	0.0245	10	407	40	-0.18	0.051	1000	-1000	-0.032	-1000
IL1-mediated signaling events	0.0245	10	649	62	-0.01	0.059	1000	-1000	-0.025	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0245	10	454	45	-0.007	0.065	1000	-1000	-0.037	-1000
a4b1 and a4b7 Integrin signaling	0.0221	9	47	5	0.013	0.027	1000	-1000	0.01	-1000
E-cadherin signaling in the nascent adherens junction	0.0221	9	698	76	-0.039	0.052	1000	-1000	-0.045	-1000
Arf6 trafficking events	0.0221	9	639	71	-0.29	0.049	1000	-1000	-0.032	-1000
Signaling events mediated by PRL	0.0221	9	306	34	-0.061	0.043	1000	-1000	-0.029	-1000
BARD1 signaling events	0.0196	8	485	57	-0.049	0.093	1000	-1000	-0.035	-1000
EPO signaling pathway	0.0196	8	476	55	-0.021	0.072	1000	-1000	-0.02	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0196	8	328	37	-0.014	0.052	1000	-1000	-0.024	-1000
TCGA08_rtk_signaling	0.0196	8	213	26	-0.04	0.06	1000	-1000	-0.013	-1000
E-cadherin signaling events	0.0196	8	42	5	0.01	0.037	1000	-1000	0.014	-1000
mTOR signaling pathway	0.0172	7	404	53	-0.029	0.037	1000	-1000	-0.029	-1000
Signaling mediated by p38-gamma and p38-delta	0.0172	7	110	15	-0.012	0.026	1000	-1000	-0.023	-1000
Syndecan-3-mediated signaling events	0.0172	7	257	35	-0.062	0.062	1000	-1000	-0.019	-1000
Class I PI3K signaling events	0.0172	7	525	73	-0.023	0.049	1000	-1000	-0.027	-1000
Regulation of Telomerase	0.0172	7	810	102	-0.12	0.083	1000	-1000	-0.051	-1000
Retinoic acid receptors-mediated signaling	0.0147	6	393	58	-0.052	0.06	1000	-1000	-0.032	-1000
E-cadherin signaling in keratinocytes	0.0147	6	283	43	-0.029	0.041	1000	-1000	-0.02	-1000
Paxillin-dependent events mediated by a4b1	0.0123	5	211	36	-0.043	0.045	1000	-1000	-0.025	-1000
Insulin-mediated glucose transport	0.0098	4	150	32	-0.14	0.048	1000	-1000	-0.022	-1000
HIF-2-alpha transcription factor network	0.0098	4	204	43	-0.12	0.12	1000	-1000	-0.048	-1000
VEGFR1 specific signals	0.0098	4	248	56	-0.053	0.069	1000	-1000	-0.033	-1000
Signaling events mediated by HDAC Class II	0.0074	3	297	75	-0.054	0.061	1000	-1000	-0.019	-1000
PLK2 and PLK4 events	0.0074	3	11	3	0.015	0.032	1000	-1000	-0.002	-1000
TRAIL signaling pathway	0.0074	3	154	48	-0.017	0.06	1000	-1000	-0.022	-1000
FoxO family signaling	0.0074	3	255	64	-0.018	0.11	1000	-1000	-0.025	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0074	3	431	125	-0.039	0.072	1000	-1000	-0.022	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0074	3	82	27	0	0.066	1000	-1000	-0.022	-1000
Canonical NF-kappaB pathway	0.0049	2	87	39	0	0.068	1000	-1000	-0.015	-1000
Arf6 downstream pathway	0.0049	2	126	43	-0.051	0.052	1000	-1000	-0.026	-1000
p38 MAPK signaling pathway	0.0049	2	125	44	-0.004	0.06	1000	-1000	-0.015	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0025	1	29	23	0.005	0.05	1000	-1000	-0.012	-1000
Circadian rhythm pathway	0.0025	1	30	22	-0.01	0.058	1000	-1000	-0.02	-1000
Signaling events mediated by HDAC Class I	0.0025	1	120	104	-0.051	0.066	1000	-1000	-0.025	-1000
Atypical NF-kappaB pathway	0.0025	1	51	31	0	0.035	1000	-1000	-0.012	-1000
Arf1 pathway	0.0025	1	54	54	0	0.048	1000	-1000	-0.011	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.072	1000	-1000	0	-1000
Total	NA	3327	201074	7203	-17	-990	131000	-131000	-3.4	-131000

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.029	0.082	-10000	0	-0.42	12	12
Crk/p130 Cas/Paxillin	-0.13	0.13	-10000	0	-0.27	159	159
JUN	-0.1	0.13	0.19	1	-0.35	29	30
HRAS	0.025	0.008	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.1	0.16	-10000	0	-0.28	178	178
RAP1A	0.028	0.003	-10000	0	-10000	0	0
FRS2	0.031	0.04	0.33	7	-10000	0	7
RAP1A/GDP	0.02	0.002	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.1	0.16	-10000	0	-0.27	180	180
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.027	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.008	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.11	0.14	-10000	0	-0.26	184	184
RHOA	0.026	0.006	-10000	0	-10000	0	0
RAP1A/GTP	-0.092	0.15	-10000	0	-0.24	182	182
GRB7	0.028	0.084	0.31	14	-0.47	7	21
RET51/GFRalpha1/GDNF	-0.1	0.16	-10000	0	-0.27	185	185
MAPKKK cascade	-0.1	0.14	-10000	0	-0.26	164	164
BCAR1	0.026	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.11	0.15	-10000	0	-0.26	189	189
lamellipodium assembly	-0.12	0.13	-10000	0	-0.25	163	163
RET51/GFRalpha1/GDNF/SHC	-0.098	0.16	-10000	0	-0.27	175	175
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.1	0.14	-10000	0	-0.26	170	170
RET9/GFRalpha1/GDNF/Shank3	-0.11	0.14	-10000	0	-0.26	184	184
MAPK3	-0.098	0.13	0.34	1	-0.23	173	174
DOK1	0.027	0.011	0.21	1	-10000	0	1
DOK6	-0.14	0.23	-10000	0	-0.47	132	132
PXN	0.027	0.004	-10000	0	-10000	0	0
neurite development	-0.12	0.14	0.3	1	-0.32	74	75
DOK5	-0.014	0.14	0.25	3	-0.47	33	36
GFRA1	-0.24	0.24	-10000	0	-0.47	216	216
MAPK8	-0.1	0.12	-10000	0	-0.24	105	105
HRAS/GTP	-0.11	0.16	-10000	0	-0.28	167	167
tube development	-0.096	0.14	0.21	8	-0.24	181	189
MAPK1	-0.097	0.13	0.34	1	-0.23	172	173
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.098	0.12	0.17	2	-0.23	170	172
Rac1/GDP	0.02	0.005	-10000	0	-10000	0	0
SRC	0.026	0.007	-10000	0	-10000	0	0
PDLIM7	0.026	0.007	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.17	0.21	-10000	0	-0.34	221	221
SHC1	0.026	0.017	0.33	1	-10000	0	1
RET51/GFRalpha1/GDNF/Dok4	-0.1	0.16	-10000	0	-0.27	184	184
RET51/GFRalpha1/GDNF/Dok5	-0.12	0.18	-10000	0	-0.29	187	187
PRKCA	0.022	0.049	-10000	0	-0.47	4	4
HRAS/GDP	0.019	0.006	-10000	0	-10000	0	0
CREB1	-0.12	0.14	-10000	0	-0.27	170	170
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.095	0.12	-10000	0	-0.23	162	162
RET51/GFRalpha1/GDNF/Grb7	-0.1	0.16	-10000	0	-0.28	179	179
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.016	0.085	0.21	7	-0.47	11	18
DOK4	0.027	0.005	-10000	0	-10000	0	0
JNK cascade	-0.099	0.12	-10000	0	-0.35	27	27
RET9/GFRalpha1/GDNF/FRS2	-0.1	0.14	0.22	4	-0.26	175	179
SHANK3	0.026	0.006	-10000	0	-10000	0	0
RASA1	0.027	0.006	-10000	0	-10000	0	0
NCK1	0.026	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.096	0.12	-10000	0	-0.23	163	163
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.099	0.13	0.21	1	-0.23	173	174
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.1	0.13	-10000	0	-0.24	175	175
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.1	0.14	-10000	0	-0.24	168	168
PI3K	-0.16	0.19	0.23	1	-0.36	176	177
SOS1	0.027	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.094	0.14	-10000	0	-0.24	181	181
GRB10	0.02	0.055	-10000	0	-0.47	5	5
activation of MAPKK activity	-0.087	0.12	-10000	0	-0.22	170	170
RET51/GFRalpha1/GDNF/FRS2	-0.1	0.16	0.35	1	-0.27	176	177
GAB1	0.026	0.006	-10000	0	-10000	0	0
IRS1	0.017	0.065	-10000	0	-0.47	7	7
IRS2	0.009	0.09	-10000	0	-0.47	14	14
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.1	0.14	-10000	0	-0.24	167	167
RET51/GFRalpha1/GDNF/PKC alpha	-0.1	0.16	-10000	0	-0.28	180	180
GRB2	0.027	0.005	-10000	0	-10000	0	0
PRKACA	0.027	0.003	-10000	0	-10000	0	0
GDNF	0.006	0.033	0.29	3	-10000	0	3
RAC1	0.026	0.006	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.11	0.16	-10000	0	-0.27	188	188
Rac1/GTP	-0.13	0.16	-10000	0	-0.29	162	162
RET9/GFRalpha1/GDNF	-0.12	0.15	-10000	0	-0.29	184	184
GFRalpha1/GDNF	-0.14	0.18	-10000	0	-0.34	184	184

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.035	0.042	0.24	12	-0.15	4	16
NFATC2	-0.11	0.26	-10000	0	-0.56	76	76
NFATC3	-0.093	0.14	-10000	0	-0.28	129	129
CD40LG	-0.48	0.52	-10000	0	-0.95	199	199
ITCH	0.005	0.079	0.25	1	-0.22	40	41
CBLB	0.007	0.078	-10000	0	-0.22	41	41
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.3	0.45	-10000	0	-1.1	70	70
JUNB	0.021	0.055	-10000	0	-0.47	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	0.01	0.096	-10000	0	-0.27	42	42
T cell anergy	-0.022	0.13	0.24	2	-0.38	41	43
TLE4	-0.079	0.21	-10000	0	-0.51	57	57
Jun/NFAT1-c-4/p21SNFT	-0.4	0.54	-10000	0	-0.93	185	185
AP-1/NFAT1-c-4	-0.53	0.64	-10000	0	-1.1	199	199
IKZF1	-0.082	0.21	-10000	0	-0.51	56	56
T-helper 2 cell differentiation	-0.22	0.34	-10000	0	-0.87	67	67
AP-1/NFAT1	-0.15	0.24	-10000	0	-0.44	128	128
CALM1	0.017	0.062	-10000	0	-10000	0	0
EGR2	-0.48	0.66	-10000	0	-1.2	158	158
EGR3	-0.68	0.75	-10000	0	-1.4	197	197
NFAT1/FOXP3	-0.059	0.21	0.35	4	-0.44	65	69
EGR1	-0.085	0.21	-10000	0	-0.47	92	92
JUN	0.003	0.094	-10000	0	-0.47	14	14
EGR4	0.017	0.081	0.21	7	-0.47	10	17
mol:Ca2+	-0.007	0.052	-10000	0	-0.16	42	42
GBP3	-0.079	0.19	-10000	0	-0.47	53	53
FOSL1	-0.006	0.12	-10000	0	-0.47	27	27
NFAT1-c-4/MAF/IRF4	-0.39	0.54	-10000	0	-0.92	183	183
DGKA	-0.074	0.18	-10000	0	-0.44	57	57
CREM	0.026	0.006	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.41	0.52	-10000	0	-0.92	182	182
CTLA4	-0.063	0.18	-10000	0	-0.43	56	56
NFAT1-c-4 (dimer)/EGR1	-0.45	0.58	-10000	0	-1	189	189
NFAT1-c-4 (dimer)/EGR4	-0.4	0.54	-10000	0	-0.93	187	187
FOS	-0.13	0.23	-10000	0	-0.47	124	124
IFNG	-0.15	0.3	-10000	0	-0.73	61	61
T cell activation	-0.23	0.3	-10000	0	-0.68	73	73
MAF	0.014	0.077	-10000	0	-0.47	10	10
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.35	0.46	0.77	187	-10000	0	187
TNF	-0.4	0.49	-10000	0	-0.88	189	189
FASLG	-0.65	0.78	-10000	0	-1.3	206	206
TBX21	0.009	0.11	0.23	1	-0.47	21	22
BATF3	0.023	0.058	0.21	4	-0.47	5	9
PRKCQ	-0.012	0.13	0.24	4	-0.47	31	35
PTPN1	-0.075	0.18	-10000	0	-0.44	57	57
NFAT1-c-4/ICER1	-0.4	0.53	-10000	0	-0.92	185	185
GATA3	-0.003	0.12	0.33	2	-0.47	24	26
T-helper 1 cell differentiation	-0.15	0.29	-10000	0	-0.71	61	61
IL2RA	-0.3	0.43	-10000	0	-0.94	91	91
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.073	0.18	-10000	0	-0.44	56	56
E2F1	0.082	0.095	0.25	97	-10000	0	97
PPARG	-0.005	0.12	0.33	2	-0.47	25	27
SLC3A2	-0.075	0.18	-10000	0	-0.44	57	57
IRF4	-0.001	0.12	0.21	3	-0.47	23	26
PTGS2	-0.5	0.54	-10000	0	-0.97	204	204
CSF2	-0.45	0.51	-10000	0	-0.92	201	201
JunB/Fra1/NFAT1-c-4	-0.4	0.53	-10000	0	-0.92	185	185
IL4	-0.23	0.36	-10000	0	-0.93	66	66
IL5	-0.46	0.5	-10000	0	-0.92	199	199
IL2	-0.23	0.3	-10000	0	-0.7	73	73
IL3	-0.072	0.15	-10000	0	-0.82	10	10
RNF128	-0.027	0.18	0.25	1	-0.55	43	44
NFATC1	-0.35	0.47	-10000	0	-0.78	187	187
CDK4	0.22	0.28	0.58	115	-10000	0	115
PTPRK	-0.074	0.18	-10000	0	-0.46	51	51
IL8	-0.48	0.52	-10000	0	-0.95	203	203
POU2F1	0.025	0.009	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.23	0.46	-10000	0	-1	99	99
MKNK1	0.027	0.004	-10000	0	-10000	0	0
MAPK14	-0.045	0.16	-10000	0	-0.31	103	103
ATF2/c-Jun	-0.059	0.18	-10000	0	-0.61	24	24
MAPK11	-0.043	0.15	-10000	0	-0.31	97	97
MITF	-0.085	0.21	-10000	0	-0.39	117	117
MAPKAPK5	-0.058	0.17	0.28	1	-0.35	100	101
KRT8	-0.068	0.19	-10000	0	-0.38	103	103
MAPKAPK3	0.026	0.006	-10000	0	-10000	0	0
MAPKAPK2	0.027	0.004	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.07	0.23	-10000	0	-0.45	103	103
CEBPB	-0.056	0.17	-10000	0	-0.36	94	94
SLC9A1	-0.062	0.18	-10000	0	-0.36	102	102
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.061	0.18	-10000	0	-0.36	100	100
p38alpha-beta/MNK1	-0.041	0.19	-10000	0	-0.37	96	96
JUN	-0.06	0.18	-10000	0	-0.6	24	24
PPARGC1A	-0.2	0.25	-10000	0	-0.4	211	211
USF1	-0.048	0.16	0.28	1	-0.35	85	86
RAB5/GDP/GDI1	-0.035	0.13	-10000	0	-0.26	91	91
NOS2	-0.064	0.21	-10000	0	-0.71	17	17
DDIT3	-0.06	0.18	-10000	0	-0.36	100	100
RAB5A	0.026	0.007	-10000	0	-10000	0	0
HSPB1	-0.049	0.14	0.29	3	-0.3	96	99
p38alpha-beta/HBP1	-0.038	0.19	-10000	0	-0.37	92	92
CREB1	-0.071	0.19	-10000	0	-0.4	100	100
RAB5/GDP	0.019	0.005	-10000	0	-10000	0	0
EIF4E	-0.056	0.16	0.24	2	-0.33	95	97
RPS6KA4	-0.063	0.18	-10000	0	-0.36	103	103
PLA2G4A	-0.072	0.18	0.24	2	-0.35	107	109
GDI1	-0.06	0.17	-10000	0	-0.36	101	101
TP53	-0.091	0.21	-10000	0	-0.44	102	102
RPS6KA5	-0.069	0.19	-10000	0	-0.38	104	104
ESR1	-0.12	0.23	-10000	0	-0.4	146	146
HBP1	0.027	0.004	-10000	0	-10000	0	0
MEF2C	-0.071	0.19	-10000	0	-0.37	109	109
MEF2A	-0.063	0.18	-10000	0	-0.36	103	103
EIF4EBP1	-0.069	0.19	-10000	0	-0.39	96	96
KRT19	-0.074	0.2	-10000	0	-0.38	107	107
ELK4	-0.061	0.17	-10000	0	-0.35	103	103
ATF6	-0.05	0.16	-10000	0	-0.35	87	87
ATF1	-0.068	0.19	-10000	0	-0.39	100	100
p38alpha-beta/MAPKAPK2	-0.04	0.19	-10000	0	-0.37	96	96
p38alpha-beta/MAPKAPK3	-0.04	0.19	-10000	0	-0.37	96	96

×

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	-0.077	0.16	0.22	1	-0.41	65	66
PTK2B	0.023	0.01	-10000	0	-10000	0	0
mol:Ca2+	-0.098	0.25	-10000	0	-0.7	44	44
EDN1	-0.021	0.084	0.34	3	-0.28	19	22
EDN3	0.001	0.037	0.23	7	-10000	0	7
EDN2	0.012	0.13	0.22	29	-0.47	22	51
HRAS/GDP	-0.14	0.25	0.28	1	-0.5	99	100
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.075	0.19	-10000	0	-0.44	65	65
ADCY4	-0.14	0.21	0.32	5	-0.33	174	179
ADCY5	-0.24	0.26	-10000	0	-0.43	232	232
ADCY6	-0.14	0.21	0.32	5	-0.33	171	176
ADCY7	-0.14	0.21	0.32	5	-0.33	174	179
ADCY1	-0.14	0.21	0.3	6	-0.34	172	178
ADCY2	-0.2	0.24	0.29	1	-0.4	202	203
ADCY3	-0.14	0.21	0.3	6	-0.34	169	175
ADCY8	-0.13	0.2	0.32	3	-0.34	156	159
ADCY9	-0.14	0.22	0.32	5	-0.34	175	180
arachidonic acid secretion	-0.18	0.28	0.33	5	-0.49	153	158
ETB receptor/Endothelin-1/Gq/GTP	-0.053	0.16	-10000	0	-0.37	70	70
GNAO1	-0.12	0.23	-10000	0	-0.47	124	124
HRAS	0.024	0.008	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.028	0.17	-10000	0	-0.38	63	63
ETA receptor/Endothelin-1/Gs/GTP	-0.13	0.22	-10000	0	-0.35	177	177
mol:GTP	-0.002	0.005	-10000	0	-10000	0	0
COL3A1	-0.083	0.2	-10000	0	-0.45	67	67
EDNRB	-0.031	0.16	-10000	0	-0.47	44	44
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.072	0.17	-10000	0	-0.43	57	57
CYSLTR1	-0.089	0.2	-10000	0	-0.48	66	66
SLC9A1	-0.035	0.093	-10000	0	-0.23	62	62
mol:GDP	-0.16	0.26	0.26	3	-0.52	106	109
SLC9A3	-0.076	0.24	-10000	0	-0.64	43	43
RAF1	-0.18	0.29	0.31	9	-0.48	158	167
JUN	-0.12	0.31	-10000	0	-0.87	46	46
JAK2	-0.073	0.16	-10000	0	-0.41	62	62
mol:IP3	-0.1	0.21	-10000	0	-0.45	89	89
ETA receptor/Endothelin-1	-0.054	0.21	-10000	0	-0.47	66	66
PLCB1	0.01	0.081	-10000	0	-0.47	11	11
PLCB2	0.02	0.037	-10000	0	-0.47	2	2
ETA receptor/Endothelin-3	-0.038	0.15	0.25	1	-0.4	49	50
FOS	-0.32	0.45	0.36	3	-0.87	150	153
Gai/GDP	-0.3	0.43	-10000	0	-0.84	145	145
CRK	0.025	0.008	-10000	0	-10000	0	0
mol:Ca ++	-0.13	0.24	-10000	0	-0.52	87	87
BCAR1	0.027	0.006	-10000	0	-10000	0	0
PRKCB1	-0.11	0.21	0.22	1	-0.44	88	89
GNAQ	0.02	0.015	-10000	0	-10000	0	0
GNAZ	-0.08	0.2	-10000	0	-0.47	87	87
GNAL	-0.17	0.24	-10000	0	-0.47	163	163
Gs family/GDP	-0.21	0.28	0.26	1	-0.51	153	154
ETA receptor/Endothelin-1/Gq/GTP	-0.069	0.18	-10000	0	-0.38	78	78
MAPK14	-0.057	0.16	0.22	2	-0.4	55	57
TRPC6	-0.1	0.27	-10000	0	-0.76	42	42
GNAI2	0.026	0.006	-10000	0	-10000	0	0
GNAI3	0.028	0.003	-10000	0	-10000	0	0
GNAI1	0.024	0.043	-10000	0	-0.47	3	3
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.054	0.16	-10000	0	-0.41	53	53
ETB receptor/Endothelin-2	-0.013	0.14	0.24	2	-0.36	56	58
ETB receptor/Endothelin-3	-0.009	0.12	0.24	1	-0.34	43	44
ETB receptor/Endothelin-1	-0.019	0.14	0.25	3	-0.35	50	53
MAPK3	-0.29	0.41	0.36	4	-0.76	155	159
MAPK1	-0.29	0.41	0.36	4	-0.75	160	164
Rac1/GDP	-0.14	0.24	-10000	0	-0.5	97	97
cAMP biosynthetic process	-0.21	0.24	0.26	5	-0.45	166	171
MAPK8	-0.13	0.32	-10000	0	-0.83	54	54
SRC	0.026	0.007	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.12	0.19	-10000	0	-0.36	128	128
p130Cas/CRK/Src/PYK2	-0.14	0.26	0.33	6	-0.56	85	91
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.14	0.24	0.26	1	-0.51	93	94
COL1A2	-0.1	0.28	-10000	0	-0.82	43	43
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.04	0.18	0.24	2	-0.38	75	77
mol:DAG	-0.1	0.21	-10000	0	-0.45	89	89
MAP2K2	-0.23	0.33	0.36	5	-0.58	164	169
MAP2K1	-0.23	0.33	0.35	4	-0.58	164	168
EDNRA	-0.085	0.19	-10000	0	-0.5	62	62
positive regulation of muscle contraction	-0.061	0.15	0.24	7	-0.36	62	69
Gq family/GDP	-0.13	0.25	0.29	1	-0.49	100	101
HRAS/GTP	-0.17	0.26	0.24	3	-0.51	116	119
PRKCH	-0.11	0.21	-10000	0	-0.46	80	80
RAC1	0.026	0.006	-10000	0	-10000	0	0
PRKCA	-0.11	0.21	0.23	5	-0.46	82	87
PRKCB	-0.17	0.25	0.25	3	-0.48	128	131
PRKCE	-0.11	0.21	-10000	0	-0.47	78	78
PRKCD	-0.11	0.21	-10000	0	-0.47	77	77
PRKCG	-0.11	0.21	0.31	2	-0.47	80	82
regulation of vascular smooth muscle contraction	-0.38	0.53	0.39	1	-1	150	151
PRKCQ	-0.12	0.23	0.25	8	-0.48	92	100
PLA2G4A	-0.2	0.31	0.35	4	-0.54	153	157
GNA14	-0.034	0.16	-10000	0	-0.47	45	45
GNA15	0.021	0.044	-10000	0	-0.47	3	3
GNA12	0.026	0.007	-10000	0	-10000	0	0
GNA11	0.023	0.027	-10000	0	-0.47	1	1
Rac1/GTP	-0.028	0.17	-10000	0	-0.38	64	64
MMP1	0.089	0.13	0.36	40	-0.78	1	41

×

IGF1 pathway

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
NCK2	0.027	0.004	-10000	0	-10000	0	0
PTK2	0.025	0.009	-10000	0	-10000	0	0
CRKL	-0.095	0.13	-10000	0	-0.25	170	170
GRB2/SOS1/SHC	0.05	0.021	0.24	1	-10000	0	1
HRAS	0.025	0.008	-10000	0	-10000	0	0
IRS1/Crk	-0.092	0.14	-10000	0	-0.24	177	177
IGF-1R heterotetramer/IGF1/PTP1B	-0.083	0.16	-10000	0	-0.27	162	162
AKT1	-0.085	0.12	0.19	11	-0.22	129	140
BAD	-0.081	0.11	0.18	11	-0.32	9	20
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.094	0.13	-10000	0	-0.24	170	170
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.088	0.14	0.21	4	-0.25	176	180
RAF1	-0.062	0.12	0.3	1	-0.41	10	11
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.068	0.15	-10000	0	-0.24	170	170
YWHAZ	0.021	0.012	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.098	0.15	-10000	0	-0.27	178	178
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
RPS6KB1	-0.082	0.12	0.19	11	-0.22	127	138
GNB2L1	0.026	0.006	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.049	0.11	0.26	2	-0.33	10	12
PXN	0.027	0.004	-10000	0	-10000	0	0
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.039	0.01	-10000	0	-10000	0	0
HRAS/GTP	-0.069	0.12	-10000	0	-0.22	149	149
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.045	0.14	-10000	0	-0.22	152	152
IGF-1R heterotetramer	-0.018	0.062	-10000	0	-0.51	2	2
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.081	0.15	-10000	0	-0.25	176	176
Crk/p130 Cas/Paxillin	-0.064	0.14	-10000	0	-0.22	170	170
IGF1R	-0.018	0.062	-10000	0	-0.51	2	2
IGF1	-0.2	0.25	-10000	0	-0.48	176	176
IRS2/Crk	-0.091	0.14	-10000	0	-0.25	169	169
PI3K	-0.066	0.14	-10000	0	-0.24	165	165
apoptosis	0.047	0.099	0.3	6	-0.22	2	8
HRAS/GDP	0.019	0.006	-10000	0	-10000	0	0
PRKCD	-0.13	0.18	0.2	2	-0.34	171	173
RAF1/14-3-3 E	-0.044	0.11	0.3	1	-0.36	10	11
BAD/14-3-3	-0.049	0.1	0.23	2	-0.32	6	8
PRKCZ	-0.086	0.12	0.19	12	-0.22	131	143
Crk/p130 Cas/Paxillin/FAK1	-0.052	0.11	-10000	0	-0.32	5	5
PTPN1	0.025	0.008	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.14	0.19	-10000	0	-0.36	176	176
BCAR1	0.026	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.059	0.15	-10000	0	-0.24	153	153
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.027	0.005	-10000	0	-10000	0	0
IRS1/NCK2	-0.089	0.14	-10000	0	-0.24	176	176
GRB10	0.02	0.055	-10000	0	-0.47	5	5
PTPN11	-0.098	0.13	-10000	0	-0.25	176	176
IRS1	-0.11	0.14	-10000	0	-0.27	178	178
IRS2	-0.1	0.14	-10000	0	-0.26	172	172
IGF-1R heterotetramer/IGF1	-0.14	0.2	-10000	0	-0.36	177	177
GRB2	0.027	0.005	-10000	0	-10000	0	0
PDPK1	-0.081	0.13	0.28	1	-0.23	160	161
YWHAE	0.025	0.008	-10000	0	-10000	0	0
PRKD1	-0.15	0.2	0.2	1	-0.36	174	175
SHC1	0.026	0.017	0.33	1	-10000	0	1

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.007	0.003	-10000	0	-10000	0	0
GNB1/GNG2	-0.066	0.15	-10000	0	-0.26	148	148
regulation of S phase of mitotic cell cycle	-0.061	0.12	-10000	0	-0.23	126	126
GNAO1	-0.12	0.23	-10000	0	-0.47	124	124
HRAS	0.024	0.008	-10000	0	-10000	0	0
SHBG/T-DHT	0.017	0.006	-10000	0	-10000	0	0
PELP1	0.024	0.008	-10000	0	-10000	0	0
AKT1	0.008	0.002	-10000	0	-10000	0	0
MAP2K1	-0.087	0.12	0.18	8	-0.25	113	121
T-DHT/AR	-0.11	0.17	-10000	0	-0.34	145	145
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.003	-10000	0	-0.006	128	128
GNAI2	0.026	0.006	-10000	0	-10000	0	0
GNAI3	0.027	0.003	-10000	0	-10000	0	0
GNAI1	0.023	0.043	-10000	0	-0.47	3	3
mol:GDP	-0.14	0.19	-10000	0	-0.38	145	145
cell proliferation	-0.16	0.21	0.26	2	-0.44	126	128
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
FOS	-0.26	0.37	-10000	0	-0.78	132	132
mol:Ca2+	-0.04	0.043	-10000	0	-0.081	181	181
MAPK3	-0.13	0.17	0.26	3	-0.34	118	121
MAPK1	-0.073	0.12	-10000	0	-0.28	49	49
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
mol:IP3	-0.001	0.002	-10000	0	-0.004	126	126
cAMP biosynthetic process	0.028	0.037	0.18	5	-10000	0	5
GNG2	0.02	0.06	-10000	0	-0.47	6	6
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	126	126
HRAS/GTP	-0.072	0.13	-10000	0	-0.25	133	133
actin cytoskeleton reorganization	0.035	0.021	-10000	0	-0.23	1	1
SRC	0.025	0.007	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	126	126
PI3K	0.032	0.02	-10000	0	-0.28	1	1
apoptosis	0.15	0.22	0.43	134	-0.25	1	135
T-DHT/AR/PELP1	-0.084	0.15	-10000	0	-0.28	146	146
HRAS/GDP	-0.12	0.18	-10000	0	-0.36	145	145
CREB1	-0.16	0.23	0.26	1	-0.46	134	135
RAC1-CDC42/GTP	0.044	0.025	-10000	0	-0.24	1	1
AR	-0.16	0.24	-10000	0	-0.47	145	145
GNB1	0.027	0.003	-10000	0	-10000	0	0
RAF1	-0.078	0.12	0.2	2	-0.25	115	117
RAC1-CDC42/GDP	-0.098	0.19	-10000	0	-0.35	143	143
T-DHT/AR/PELP1/Src	-0.065	0.14	-10000	0	-0.26	133	133
MAP2K2	-0.088	0.12	0.18	8	-0.25	116	124
T-DHT/AR/PELP1/Src/PI3K	-0.061	0.12	-10000	0	-0.24	126	126
GNAZ	-0.08	0.2	-10000	0	-0.47	87	87
SHBG	0.023	0.012	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.16	0.22	-10000	0	-0.46	125	125
mol:T-DHT	0	0.001	-10000	0	-0.003	64	64
RAC1	0.026	0.006	-10000	0	-10000	0	0
GNRH1	0.006	0.003	-10000	0	-10000	0	0
Gi family/GTP	-0.15	0.18	-10000	0	-0.33	159	159
CDC42	0.028	0.003	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.028	0.2	-10000	0	-0.56	47	47
IHH	0.034	0.1	0.26	30	-0.26	17	47
SHH Np/Cholesterol/GAS1	-0.12	0.16	-10000	0	-0.28	186	186
LRPAP1	0.027	0.016	0.33	1	-10000	0	1
dorsoventral neural tube patterning	0.12	0.15	0.28	186	-10000	0	186
SMO/beta Arrestin2	-0.037	0.16	-10000	0	-0.44	33	33
SMO	-0.053	0.16	-10000	0	-0.4	51	51
AKT1	-0.019	0.14	-10000	0	-0.56	15	15
ARRB2	0.025	0.008	-10000	0	-10000	0	0
BOC	-0.016	0.14	0.21	1	-0.47	35	36
ADRBK1	0.027	0.005	-10000	0	-10000	0	0
heart looping	-0.052	0.16	-10000	0	-0.4	51	51
STIL	-0.084	0.15	-10000	0	-0.31	68	68
DHH N/PTCH2	0.005	0.11	-10000	0	-0.34	36	36
DHH N/PTCH1	-0.007	0.13	-10000	0	-0.3	61	61
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
DHH	0	0.1	-10000	0	-0.47	19	19
PTHLH	-0.069	0.31	-10000	0	-0.89	48	48
determination of left/right symmetry	-0.052	0.16	-10000	0	-0.4	51	51
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
skeletal system development	-0.068	0.31	-10000	0	-0.88	48	48
IHH N/Hhip	-0.061	0.19	-10000	0	-0.38	100	100
DHH N/Hhip	-0.068	0.17	-10000	0	-0.35	109	109
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.052	0.16	-10000	0	-0.4	51	51
pancreas development	-0.098	0.21	0.21	1	-0.47	97	98
HHAT	0.027	0.004	-10000	0	-10000	0	0
PI3K	0.035	0.023	-10000	0	-0.34	1	1
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.055	0.18	0.21	2	-0.47	66	68
somite specification	-0.052	0.16	-10000	0	-0.4	51	51
SHH Np/Cholesterol/PTCH1	-0.088	0.15	-10000	0	-0.26	151	151
SHH Np/Cholesterol/PTCH2	-0.086	0.14	-10000	0	-0.27	151	151
SHH Np/Cholesterol/Megalin	-0.065	0.15	0.23	2	-0.26	139	141
SHH	-0.11	0.16	-10000	0	-0.34	140	140
catabolic process	-0.006	0.12	-10000	0	-0.32	50	50
SMO/Vitamin D3	-0.092	0.17	-10000	0	-0.38	57	57
SHH Np/Cholesterol/Hhip	-0.14	0.17	-10000	0	-0.3	197	197
LRP2	0.06	0.08	0.22	81	-10000	0	81
receptor-mediated endocytosis	-0.098	0.17	-10000	0	-0.41	44	44
SHH Np/Cholesterol/BOC	-0.092	0.15	-10000	0	-0.27	155	155
SHH Np/Cholesterol/CDO	-0.11	0.15	-10000	0	-0.27	175	175
mesenchymal cell differentiation	0.14	0.17	0.3	197	-10000	0	197
mol:Vitamin D3	-0.084	0.16	-10000	0	-0.26	137	137
IHH N/PTCH2	0.019	0.11	0.21	1	-0.34	26	27
CDON	-0.033	0.16	-10000	0	-0.47	48	48
IHH N/PTCH1	0.01	0.14	-10000	0	-0.32	51	51
Megalin/LRPAP1	0.063	0.058	0.24	4	-0.16	2	6
PTCH2	0.004	0.1	-10000	0	-0.47	19	19
SHH Np/Cholesterol	-0.081	0.13	-10000	0	-0.26	141	141
PTCH1	-0.006	0.12	-10000	0	-0.32	50	50
HHIP	-0.098	0.21	0.21	1	-0.47	97	98

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.43	0.58	-10000	0	-1.2	118	118
STAT6 (cleaved dimer)	-0.48	0.6	-10000	0	-1.2	136	136
IGHG1	-0.12	0.2	-10000	0	-0.36	71	71
IGHG3	-0.44	0.55	-10000	0	-1.1	135	135
AKT1	-0.2	0.33	-10000	0	-0.78	56	56
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.15	0.3	-10000	0	-0.76	45	45
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.22	0.35	-10000	0	-0.75	69	69
THY1	-0.45	0.58	-10000	0	-1.2	122	122
MYB	0.053	0.076	0.23	56	-0.47	1	57
HMGA1	0.031	0.026	0.21	8	-10000	0	8
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.28	0.41	-10000	0	-0.74	123	123
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.22	0.36	-10000	0	-0.76	68	68
SP1	0.025	0.031	-10000	0	-10000	0	0
INPP5D	0.018	0.06	-10000	0	-0.47	6	6
SOCS5	0.03	0.033	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.46	0.6	-10000	0	-1.2	134	134
SOCS1	-0.28	0.37	-10000	0	-0.73	115	115
SOCS3	-0.29	0.46	-10000	0	-1.2	61	61
FCER2	-0.68	0.74	-10000	0	-1.4	192	192
PARP14	0.016	0.026	-10000	0	-10000	0	0
CCL17	-0.44	0.58	-10000	0	-1.2	122	122
GRB2	0.027	0.005	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.16	0.28	-10000	0	-0.68	43	43
T cell proliferation	-0.46	0.6	-10000	0	-1.2	125	125
IL4R/JAK1	-0.45	0.58	-10000	0	-1.2	124	124
EGR2	-0.62	0.73	-10000	0	-1.4	153	153
JAK2	-0.012	0.051	-10000	0	-10000	0	0
JAK3	0.026	0.023	0.22	2	-10000	0	2
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
JAK1	0.009	0.029	-10000	0	-10000	0	0
COL1A2	-0.18	0.39	-10000	0	-1.5	28	28
CCL26	-0.46	0.59	-10000	0	-1.2	120	120
IL4R	-0.48	0.62	-10000	0	-1.3	121	121
PTPN6	0.031	0.026	0.2	1	-10000	0	1
IL13RA2	-0.47	0.6	-10000	0	-1.2	128	128
IL13RA1	-0.014	0.054	-10000	0	-10000	0	0
IRF4	-0.23	0.48	-10000	0	-1.1	69	69
ARG1	-0.098	0.21	-10000	0	-0.63	23	23
CBL	-0.26	0.38	-10000	0	-0.71	119	119
GTF3A	0.03	0.021	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.012	0.073	-10000	0	-10000	0	0
IRF4/BCL6	-0.19	0.44	-10000	0	-1.1	64	64
CD40LG	-0.035	0.15	0.25	1	-0.47	43	44
MAPK14	-0.28	0.43	-10000	0	-0.86	96	96
mitosis	-0.19	0.31	-10000	0	-0.73	56	56
STAT6	-0.54	0.74	-10000	0	-1.4	132	132
SPI1	0.026	0.059	0.21	5	-0.46	5	10
RPS6KB1	-0.18	0.3	-10000	0	-0.69	55	55
STAT6 (dimer)	-0.53	0.73	-10000	0	-1.4	132	132
STAT6 (dimer)/PARP14	-0.52	0.66	-10000	0	-1.3	136	136
mast cell activation	0.009	0.015	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.22	0.36	-10000	0	-0.8	66	66
FRAP1	-0.2	0.33	-10000	0	-0.78	56	56
LTA	-0.46	0.6	-10000	0	-1.2	123	123
FES	0.027	0.004	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.51	0.68	1.3	132	-10000	0	132
CCL11	-0.47	0.61	-10000	0	-1.2	125	125
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.2	0.34	-10000	0	-0.8	54	54
IL2RG	0.018	0.08	0.21	9	-0.46	9	18
IL10	-0.47	0.61	-10000	0	-1.2	127	127
IRS1	0.017	0.065	-10000	0	-0.47	7	7
IRS2	0.009	0.09	-10000	0	-0.47	14	14
IL4	-0.1	0.22	-10000	0	-1.1	11	11
IL5	-0.45	0.58	-10000	0	-1.2	122	122
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.36	0.48	-10000	0	-0.93	129	129
COL1A1	-0.14	0.32	-10000	0	-1.6	13	13
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.46	0.6	-10000	0	-1.3	115	115
IL2R gamma/JAK3	0.029	0.067	0.33	2	-0.34	9	11
TFF3	-0.58	0.71	-10000	0	-1.4	153	153
ALOX15	-0.44	0.58	-10000	0	-1.2	120	120
MYBL1	0.027	0.02	0.21	4	-10000	0	4
T-helper 2 cell differentiation	-0.39	0.5	-10000	0	-0.98	133	133
SHC1	0.026	0.017	0.33	1	-10000	0	1
CEBPB	0.028	0.027	-10000	0	-0.47	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.2	0.33	-10000	0	-0.68	74	74
mol:PI-3-4-5-P3	-0.2	0.33	-10000	0	-0.78	56	56
PI3K	-0.22	0.36	-10000	0	-0.86	56	56
DOK2	0.014	0.07	0.21	2	-0.47	8	10
ETS1	0.025	0.031	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.14	0.25	-10000	0	-0.62	38	38
ITGB3	-0.5	0.65	-10000	0	-1.3	132	132
PIGR	-0.71	0.73	-10000	0	-1.4	206	206
IGHE	0.033	0.065	0.16	28	-0.31	1	29
MAPKKK cascade	-0.14	0.25	-10000	0	-0.61	38	38
BCL6	0.031	0.012	-10000	0	-10000	0	0
OPRM1	-0.45	0.58	-10000	0	-1.2	118	118
RETNLB	-0.45	0.58	-10000	0	-1.2	116	116
SELP	-0.55	0.7	-10000	0	-1.4	145	145
AICDA	-0.43	0.55	-10000	0	-1.1	122	122

×

Reelin signaling pathway

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
CDK5R1/CDK5	0.046	0.034	0.24	4	-10000	0	4
VLDLR	0.012	0.077	-10000	0	-0.47	10	10
CRKL	0.028	0.014	0.21	2	-10000	0	2
LRPAP1	0.027	0.016	0.33	1	-10000	0	1
FYN	0.022	0.043	-10000	0	-0.47	3	3
ITGA3	0.031	0.027	0.23	7	-10000	0	7
RELN/VLDLR/Fyn	-0.071	0.16	-10000	0	-0.28	142	142
MAPK8IP1/MKK7/MAP3K11/JNK1	0.062	0.047	-10000	0	-0.24	4	4
AKT1	-0.083	0.14	-10000	0	-0.26	141	141
MAP2K7	0.027	0.005	-10000	0	-10000	0	0
RAPGEF1	0.025	0.009	-10000	0	-10000	0	0
DAB1	-0.016	0.14	0.22	25	-0.47	33	58
RELN/LRP8/DAB1	-0.068	0.18	0.27	4	-0.28	156	160
LRPAP1/LRP8	0.062	0.052	0.17	69	-10000	0	69
RELN/LRP8/DAB1/Fyn	-0.06	0.18	0.27	4	-0.27	158	162
DAB1/alpha3/beta1 Integrin	-0.06	0.16	0.24	1	-0.25	148	149
long-term memory	-0.1	0.22	0.28	4	-0.32	180	184
DAB1/LIS1	-0.054	0.17	0.26	2	-0.26	153	155
DAB1/CRLK/C3G	-0.058	0.16	-10000	0	-0.26	144	144
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
DAB1/NCK2	-0.051	0.18	0.26	3	-0.26	153	156
ARHGEF2	0.026	0.008	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.08	0.2	0.21	3	-0.47	81	84
CDK5R1	0.038	0.05	0.24	22	-10000	0	22
RELN	-0.15	0.23	0.21	4	-0.47	139	143
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
RELN/LRP8/Fyn	-0.055	0.18	0.29	3	-0.29	139	142
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.11	0.22	0.4	1	-0.32	183	184
MAPK8	0.023	0.043	-10000	0	-0.47	3	3
RELN/VLDLR/DAB1	-0.08	0.17	0.22	1	-0.28	157	158
ITGB1	0.026	0.006	-10000	0	-10000	0	0
MAP1B	-0.12	0.17	0.33	2	-0.3	173	175
RELN/LRP8	-0.051	0.18	0.27	5	-0.29	135	140
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.052	0.19	0.28	4	-0.27	156	160
PI3K	0.035	0.023	-10000	0	-0.34	1	1
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.04	0.021	0.24	1	-10000	0	1
RAP1A	-0.086	0.14	0.37	5	-0.33	31	36
PAFAH1B1	0.025	0.008	-10000	0	-10000	0	0
MAPK8IP1	0.025	0.027	0.21	1	-0.47	1	2
CRLK/C3G	0.036	0.017	-10000	0	-10000	0	0
GRIN2B	0.004	0.042	0.21	12	-10000	0	12
NCK2	0.027	0.004	-10000	0	-10000	0	0
neuron differentiation	-0.053	0.12	0.19	1	-0.31	38	39
neuron adhesion	-0.075	0.14	0.34	7	-0.42	12	19
LRP8	0.062	0.073	0.22	74	-10000	0	74
GSK3B	-0.079	0.13	-10000	0	-0.33	42	42
RELN/VLDLR/DAB1/Fyn	-0.07	0.16	-10000	0	-0.26	159	159
MAP3K11	0.027	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.085	0.15	0.17	1	-0.27	146	147
CDK5	0.027	0.004	-10000	0	-10000	0	0
MAPT	-0.01	0.17	0.76	9	-0.42	33	42
neuron migration	-0.099	0.16	0.33	5	-0.31	127	132
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.053	0.12	0.19	1	-0.32	38	39
RELN/VLDLR	-0.043	0.17	0.28	4	-0.27	136	140

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.053	0.075	0.2	13	-0.25	3	16
STMN1	0.026	0.051	0.38	3	-10000	0	3
Aurora B/RasGAP/Survivin	0.18	0.12	0.3	167	-0.19	4	171
Chromosomal passenger complex/Cul3 protein complex	-0.011	0.12	0.22	6	-0.28	30	36
BIRC5	0.16	0.095	0.22	288	-0.48	1	289
DES	-0.32	0.31	-10000	0	-0.53	253	253
Aurora C/Aurora B/INCENP	0.1	0.07	0.25	7	-10000	0	7
Aurora B/TACC1	0.071	0.072	0.16	142	-0.18	6	148
Aurora B/PP2A	0.095	0.073	0.18	108	-0.15	3	111
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.019	0.02	0.13	6	-0.1	3	9
mitotic metaphase/anaphase transition	-0.002	0.004	-10000	0	-10000	0	0
NDC80	0.021	0.1	0.36	26	-0.19	2	28
Cul3 protein complex	-0.028	0.13	-10000	0	-0.28	83	83
KIF2C	0.078	0.057	0.16	55	-0.14	1	56
PEBP1	0.027	0.005	-10000	0	-10000	0	0
KIF20A	0.16	0.086	0.21	289	-10000	0	289
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.094	0.074	0.18	115	-0.15	3	118
SEPT1	0.027	0.03	0.21	3	-0.47	1	4
SMC2	0.025	0.013	0.21	1	-10000	0	1
SMC4	0.026	0.006	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	0.039	0.19	0.26	4	-0.55	33	37
PSMA3	0.027	0.004	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.004	0.004	-10000	0	-10000	0	0
H3F3B	0.038	0.036	0.2	3	-0.2	3	6
AURKB	0.12	0.099	0.23	178	-10000	0	178
AURKC	0.033	0.033	0.21	13	-10000	0	13
CDCA8	0.083	0.088	0.23	108	-10000	0	108
cytokinesis	0.06	0.084	0.25	6	-0.32	9	15
Aurora B/Septin1	0.11	0.13	0.29	23	-0.28	19	42
AURKA	0.085	0.093	0.22	122	-10000	0	122
INCENP	0.031	0.011	0.22	1	-10000	0	1
KLHL13	-0.077	0.2	-10000	0	-0.47	85	85
BUB1	0.064	0.077	0.22	79	-10000	0	79
hSgo1/Aurora B/Survivin	0.22	0.15	0.34	220	-0.2	3	223
EVI5	0.03	0.005	-10000	0	-10000	0	0
RhoA/GTP	0.13	0.11	0.26	81	-0.3	1	82
SGOL1	0.11	0.1	0.22	170	-10000	0	170
CENPA	0.082	0.088	0.23	29	-0.25	5	34
NCAPG	0.11	0.093	0.21	177	-10000	0	177
Aurora B/HC8 Proteasome	0.097	0.073	0.19	14	-0.15	3	17
NCAPD2	0.028	0.016	0.33	1	-10000	0	1
Aurora B/PP1-gamma	0.097	0.073	0.18	70	-0.15	2	72
RHOA	0.026	0.006	-10000	0	-10000	0	0
NCAPH	0.14	0.094	0.22	249	-10000	0	249
NPM1	0.013	0.14	0.24	2	-0.39	32	34
RASA1	0.027	0.006	-10000	0	-10000	0	0
KLHL9	0.022	0.011	-10000	0	-10000	0	0
mitotic prometaphase	-0.001	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.097	0.073	0.19	13	-0.15	3	16
PPP1CC	0.027	0.005	-10000	0	-10000	0	0
Centraspindlin	0.14	0.11	0.27	126	-0.28	2	128
RhoA/GDP	0.02	0.005	-10000	0	-10000	0	0
NSUN2	0.039	0.11	0.24	2	-0.3	29	31
MYLK	-0.078	0.17	0.19	3	-0.32	133	136
KIF23	0.12	0.095	0.22	197	-10000	0	197
VIM	0.037	0.067	0.3	13	-0.36	4	17
RACGAP1	0.033	0.02	0.22	4	-10000	0	4
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.007	0.17	0.24	1	-0.46	33	34
Chromosomal passenger complex	0.074	0.074	0.2	31	-0.26	3	34
Chromosomal passenger complex/EVI5	0.24	0.15	0.37	189	-0.25	1	190
TACC1	0.021	0.036	-10000	0	-0.47	2	2
PPP2R5D	0.027	0.004	-10000	0	-10000	0	0
CUL3	0.025	0.008	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

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

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
MAP4K1	-0.072	0.18	0.26	1	-0.4	84	85
CRKL	-0.08	0.18	-10000	0	-0.41	87	87
HRAS	-0.076	0.19	-10000	0	-0.38	90	90
mol:PIP3	-0.078	0.18	-10000	0	-0.38	93	93
SPRED1	0.027	0.005	-10000	0	-10000	0	0
SPRED2	0.027	0.005	-10000	0	-10000	0	0
GAB1	-0.09	0.19	-10000	0	-0.42	93	93
FOXO3	-0.074	0.18	-10000	0	-0.38	90	90
AKT1	-0.079	0.19	-10000	0	-0.41	91	91
BAD	-0.073	0.18	-10000	0	-0.38	87	87
megakaryocyte differentiation	-0.091	0.19	-10000	0	-0.42	94	94
GSK3B	-0.069	0.18	0.32	1	-0.38	85	86
RAF1	-0.055	0.15	0.25	4	-0.32	75	79
SHC1	0.026	0.017	0.33	1	-10000	0	1
STAT3	-0.091	0.19	-10000	0	-0.42	92	92
STAT1	-0.22	0.45	-10000	0	-1	92	92
HRAS/SPRED1	-0.052	0.16	0.24	1	-0.32	85	86
cell proliferation	-0.09	0.19	-10000	0	-0.42	91	91
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
TEC	0.027	0.004	-10000	0	-10000	0	0
RPS6KB1	-0.08	0.2	-10000	0	-0.42	93	93
HRAS/SPRED2	-0.051	0.16	0.24	1	-0.32	83	84
LYN/TEC/p62DOK	-0.051	0.19	-10000	0	-0.4	80	80
MAPK3	-0.026	0.13	0.25	10	-0.27	33	43
STAP1	-0.1	0.2	-10000	0	-0.44	97	97
GRAP2	-0.026	0.15	-10000	0	-0.47	43	43
JAK2	-0.18	0.39	-10000	0	-0.87	93	93
STAT1 (dimer)	-0.22	0.44	-10000	0	-0.98	94	94
mol:Gleevec	0.002	0.008	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.062	0.21	-10000	0	-0.42	90	90
actin filament polymerization	-0.088	0.19	-10000	0	-0.42	91	91
LYN	0.025	0.008	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.14	0.27	-10000	0	-0.6	95	95
PIK3R1	0.025	0.026	-10000	0	-0.47	1	1
CBL/CRKL/GRB2	-0.053	0.18	-10000	0	-0.38	85	85
PI3K	-0.058	0.2	-10000	0	-0.4	84	84
PTEN	0.026	0.007	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.24	0.54	-10000	0	-1.2	90	90
MAPK8	-0.092	0.19	-10000	0	-0.43	91	91
STAT3 (dimer)	-0.089	0.19	-10000	0	-0.42	92	92
positive regulation of transcription	-0.018	0.11	0.23	10	-0.22	28	38
mol:GDP	-0.075	0.19	-10000	0	-0.4	88	88
PIK3C2B	-0.091	0.19	-10000	0	-0.43	93	93
CBL/CRKL	-0.064	0.18	-10000	0	-0.39	87	87
FER	-0.092	0.19	-10000	0	-0.43	93	93
SH2B3	-0.087	0.19	-10000	0	-0.42	92	92
PDPK1	-0.071	0.17	-10000	0	-0.36	89	89
SNAI2	-0.091	0.19	-10000	0	-0.43	87	87
positive regulation of cell proliferation	-0.16	0.32	-10000	0	-0.73	94	94
KITLG	0.009	0.063	-10000	0	-0.49	5	5
cell motility	-0.16	0.32	-10000	0	-0.73	94	94
PTPN6	0.031	0.015	0.21	1	-10000	0	1
EPOR	-0.071	0.24	-10000	0	-0.93	16	16
STAT5A (dimer)	-0.13	0.27	-10000	0	-0.6	95	95
SOCS1	0.027	0.011	0.21	1	-10000	0	1
cell migration	0.1	0.2	0.44	97	-10000	0	97
SOS1	0.027	0.005	-10000	0	-10000	0	0
EPO	0.03	0.058	0.22	31	-10000	0	31
VAV1	0.008	0.097	0.21	2	-0.47	16	18
GRB10	-0.093	0.19	-10000	0	-0.43	91	91
PTPN11	0.029	0.01	-10000	0	-10000	0	0
SCF/KIT	-0.094	0.2	-10000	0	-0.45	94	94
GO:0007205	0.004	0.01	-10000	0	-10000	0	0
MAP2K1	-0.032	0.13	0.26	9	-0.29	35	44
CBL	0.026	0.007	-10000	0	-10000	0	0
KIT	-0.28	0.56	-10000	0	-1.3	94	94
MAP2K2	-0.03	0.14	0.26	10	-0.28	36	46
SHC/Grb2/SOS1	-0.05	0.19	-10000	0	-0.4	77	77
STAT5A	-0.13	0.28	-10000	0	-0.61	95	95
GRB2	0.027	0.005	-10000	0	-10000	0	0
response to radiation	-0.088	0.19	0.28	1	-0.42	87	88
SHC/GRAP2	0.004	0.11	0.24	1	-0.34	36	37
PTPRO	-0.092	0.19	-10000	0	-0.43	94	94
SH2B2	-0.09	0.19	-10000	0	-0.42	91	91
DOK1	0.027	0.011	0.21	1	-10000	0	1
MATK	-0.1	0.2	-10000	0	-0.44	97	97
CREBBP	0.01	0.064	-10000	0	-0.17	7	7
BCL2	-0.13	0.37	-10000	0	-1.1	41	41

×

Thromboxane A2 receptor signaling

Figure S12. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S12. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.015	0.086	0.23	7	-0.47	11	18
GNB1/GNG2	-0.081	0.09	-10000	0	-0.19	163	163
AKT1	-0.059	0.13	0.28	5	-0.24	32	37
EGF	0.034	0.047	0.21	24	-10000	0	24
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.008	0.063	0.28	1	-0.33	1	2
mol:Ca2+	-0.098	0.18	0.32	4	-0.3	170	174
LYN	0.008	0.058	0.28	1	-0.33	1	2
RhoA/GTP	-0.04	0.077	0.17	3	-0.13	138	141
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.12	0.2	0.33	4	-0.34	163	167
GNG2	0.02	0.06	-10000	0	-0.47	6	6
ARRB2	0.025	0.008	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.03	0.14	-10000	0	-0.47	24	24
G beta5/gamma2	-0.1	0.12	-10000	0	-0.25	157	157
PRKCH	-0.12	0.2	0.37	2	-0.34	165	167
DNM1	0.017	0.06	-10000	0	-0.47	6	6
TXA2/TP beta/beta Arrestin3	0.001	0.075	-10000	0	-0.55	6	6
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	0.001	0.1	-10000	0	-0.47	18	18
G12 family/GTP	-0.11	0.16	-10000	0	-0.3	154	154
ADRBK1	0.027	0.005	-10000	0	-10000	0	0
ADRBK2	0.026	0.029	0.33	1	-0.47	1	2
RhoA/GTP/ROCK1	0.034	0.011	-10000	0	-10000	0	0
mol:GDP	0.049	0.12	0.32	22	-0.24	3	25
mol:NADP	0.027	0.01	0.21	1	-10000	0	1
RAB11A	0.027	0.004	-10000	0	-10000	0	0
PRKG1	-0.082	0.2	-10000	0	-0.47	87	87
mol:IP3	-0.13	0.22	0.4	2	-0.37	170	172
cell morphogenesis	0.033	0.011	-10000	0	-10000	0	0
PLCB2	-0.18	0.29	0.42	2	-0.5	168	170
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.005	0.081	0.28	1	-0.26	4	5
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.004	0.067	0.26	2	-0.27	8	10
RHOA	0.026	0.006	-10000	0	-10000	0	0
PTGIR	0.026	0.025	-10000	0	-0.47	1	1
PRKCB1	-0.13	0.21	0.38	2	-0.37	167	169
GNAQ	0.025	0.009	-10000	0	-10000	0	0
mol:L-citrulline	0.027	0.01	0.21	1	-10000	0	1
TXA2/TXA2-R family	-0.19	0.29	0.43	2	-0.52	166	168
LCK	0.007	0.067	0.28	1	-0.32	3	4
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.02	0.055	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.022	0.059	-10000	0	-0.37	6	6
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.024	0.055	-10000	0	-10000	0	0
MAPK14	-0.072	0.14	0.27	4	-0.23	162	166
TGM2/GTP	-0.15	0.24	0.42	3	-0.42	156	159
MAPK11	-0.073	0.14	0.27	4	-0.23	162	166
ARHGEF1	-0.057	0.1	0.22	3	-0.18	143	146
GNAI2	0.026	0.006	-10000	0	-10000	0	0
JNK cascade	-0.13	0.22	0.35	4	-0.38	166	170
RAB11/GDP	0.027	0.004	-10000	0	-10000	0	0
ICAM1	-0.09	0.17	0.31	4	-0.28	165	169
cAMP biosynthetic process	-0.12	0.2	0.35	3	-0.35	163	166
Gq family/GTP/EBP50	-0.02	0.087	0.25	1	-0.19	76	77
actin cytoskeleton reorganization	0.033	0.011	-10000	0	-10000	0	0
SRC	0.007	0.06	0.28	1	-0.33	1	2
GNB5	0.027	0.004	-10000	0	-10000	0	0
GNB1	0.027	0.003	-10000	0	-10000	0	0
EGF/EGFR	0.015	0.084	0.24	14	-0.26	7	21
VCAM1	-0.1	0.18	0.31	4	-0.3	165	169
TP beta/Gq family/GDP/G beta5/gamma2	-0.03	0.14	-10000	0	-0.47	24	24
platelet activation	-0.096	0.18	0.34	4	-0.3	163	167
PGI2/IP	0.019	0.018	-10000	0	-0.34	1	1
PRKACA	0.007	0.054	-10000	0	-0.24	19	19
Gq family/GDP/G beta5/gamma2	-0.029	0.13	-10000	0	-0.44	24	24
TXA2/TP beta/beta Arrestin2	-0.016	0.11	-10000	0	-0.39	28	28
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.001	0.051	0.2	1	-0.22	19	20
mol:DAG	-0.14	0.24	0.4	2	-0.41	167	169
EGFR	0.021	0.085	0.33	8	-0.47	9	17
TXA2/TP alpha	-0.17	0.27	0.44	2	-0.48	162	164
Gq family/GTP	-0.02	0.089	0.23	2	-0.23	57	59
YES1	0.009	0.06	0.28	1	-0.33	1	2
GNAI2/GTP	0.011	0.052	-10000	0	-0.24	4	4
PGD2/DP	0.002	0.073	-10000	0	-0.33	18	18
SLC9A3R1	0.036	0.041	0.21	21	-10000	0	21
FYN	0.007	0.065	0.28	1	-0.35	2	3
mol:NO	0.027	0.01	0.21	1	-10000	0	1
GNA15	0.023	0.043	-10000	0	-0.47	3	3
PGK/cGMP	-0.034	0.13	-10000	0	-0.28	86	86
RhoA/GDP	0.027	0.006	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.031	0.091	-10000	0	-0.42	7	7
NOS3	0.028	0.01	0.21	1	-10000	0	1
RAC1	0.026	0.006	-10000	0	-10000	0	0
PRKCA	-0.12	0.2	0.34	3	-0.34	156	159
PRKCB	-0.16	0.23	0.5	1	-0.4	165	166
PRKCE	-0.11	0.2	0.35	4	-0.34	158	162
PRKCD	-0.13	0.22	0.36	3	-0.38	165	168
PRKCG	-0.13	0.22	0.38	3	-0.38	162	165
muscle contraction	-0.17	0.27	0.42	3	-0.48	166	169
PRKCZ	-0.12	0.2	0.33	4	-0.34	165	169
ARR3	-0.009	0.018	-10000	0	-10000	0	0
TXA2/TP beta	0.025	0.061	-10000	0	-0.23	10	10
PRKCQ	-0.12	0.22	0.33	8	-0.36	158	166
MAPKKK cascade	-0.16	0.26	0.4	2	-0.45	168	170
SELE	-0.14	0.22	0.31	4	-0.39	165	169
TP beta/GNAI2/GDP/G beta/gamma	0.037	0.068	-10000	0	-0.33	2	2
ROCK1	0.027	0.006	-10000	0	-10000	0	0
GNA14	-0.03	0.16	-10000	0	-0.47	45	45
chemotaxis	-0.22	0.33	0.46	2	-0.61	165	167
GNA12	0.026	0.007	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
GNA11	0.026	0.025	-10000	0	-0.47	1	1
Rac1/GTP	0.019	0.005	-10000	0	-10000	0	0

×

p75(NTR)-mediated 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
Sortilin/TRAF6	0.038	0.012	-10000	0	-10000	0	0
Necdin/E2F1	0.027	0.14	0.24	20	-0.34	39	59
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.028	0.17	-10000	0	-0.29	114	114
NGF (dimer)/p75(NTR)/BEX1	-0.078	0.2	0.35	1	-0.35	132	133
NT-4/5 (dimer)/p75(NTR)	-0.061	0.18	0.24	1	-0.36	103	104
IKBKB	0.025	0.009	-10000	0	-10000	0	0
AKT1	-0.058	0.15	0.19	1	-0.28	105	106
IKBKG	0.027	0.004	-10000	0	-10000	0	0
BDNF	-0.056	0.18	-10000	0	-0.47	67	67
MGDIs/NGR/p75(NTR)/LINGO1	0.001	0.16	0.29	10	-0.29	84	94
FURIN	0.028	0.01	0.21	1	-10000	0	1
proBDNF (dimer)/p75(NTR)/Sortilin	-0.071	0.18	0.24	1	-0.32	131	132
LINGO1	0.035	0.038	0.21	18	-10000	0	18
Sortilin/TRAF6/NRIF	0.026	0.018	-10000	0	-10000	0	0
proBDNF (dimer)	-0.056	0.18	-10000	0	-0.47	67	67
NTRK1	0.025	0.031	0.23	7	-10000	0	7
RTN4R	0.055	0.07	0.22	60	-10000	0	60
neuron apoptosis	-0.079	0.19	0.35	3	-0.46	49	52
IRAK1	0.027	0.004	-10000	0	-10000	0	0
SHC1	-0.071	0.16	0.23	1	-0.33	101	102
ARHGDIA	0.027	0.005	-10000	0	-10000	0	0
RhoA/GTP	0.02	0.005	-10000	0	-10000	0	0
Gamma Secretase	0.062	0.036	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.038	0.18	0.24	1	-0.3	116	117
MAGEH1	0.025	0.035	-10000	0	-0.47	2	2
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.068	0.2	0.24	1	-0.33	136	137
Mammalian IAPs/DIABLO	0.05	0.072	0.24	1	-0.26	18	19
proNGF (dimer)	-0.039	0.17	-10000	0	-0.47	53	53
MAGED1	0.027	0.003	-10000	0	-10000	0	0
APP	0.026	0.025	-10000	0	-0.47	1	1
NT-4/5 (dimer)	-0.007	0.12	-10000	0	-0.47	27	27
ZNF274	0.027	0.005	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.053	0.15	-10000	0	-0.28	113	113
NGF	-0.039	0.17	-10000	0	-0.47	53	53
cell cycle arrest	-0.071	0.14	0.24	11	-0.26	115	126
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.05	0.14	-10000	0	-0.28	93	93
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.037	0.16	0.24	1	-0.3	99	100
NCSTN	0.024	0.01	-10000	0	-10000	0	0
mol:GTP	-0.057	0.18	0.23	1	-0.33	117	118
PSENEN	0.027	0.006	-10000	0	-10000	0	0
mol:ceramide	-0.07	0.15	0.2	1	-0.3	115	116
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.042	0.12	0.24	1	-0.38	30	31
p75(NTR)/beta APP	-0.037	0.15	0.24	1	-0.34	84	85
BEX1	-0.016	0.14	0.21	6	-0.47	32	38
mol:GDP	-0.09	0.16	0.22	1	-0.33	116	117
NGF (dimer)	0.023	0.14	0.24	6	-0.28	67	73
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.015	0.15	0.29	8	-0.26	82	90
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
RAC1/GTP	-0.045	0.15	0.21	1	-0.28	113	114
MYD88	0.026	0.006	-10000	0	-10000	0	0
CHUK	0.027	0.005	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.057	0.18	0.24	1	-0.33	117	118
RHOB	0.027	0.005	-10000	0	-10000	0	0
RHOA	0.026	0.006	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.071	0.066	0.24	24	-10000	0	24
NT3 (dimer)	-0.063	0.19	0.21	1	-0.47	72	73
TP53	-0.066	0.14	0.35	3	-0.26	122	125
PRDM4	-0.071	0.16	0.2	1	-0.3	115	116
BDNF (dimer)	-0.026	0.19	0.29	6	-0.31	112	118
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
SORT1	0.028	0.002	-10000	0	-10000	0	0
activation of caspase activity	-0.032	0.17	-10000	0	-0.28	114	114
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.038	0.17	0.24	1	-0.3	114	115
RHOC	0.028	0.002	-10000	0	-10000	0	0
XIAP	0.028	0.015	0.33	1	-10000	0	1
MAPK10	-0.11	0.18	0.39	1	-0.38	97	98
DIABLO	0.027	0.004	-10000	0	-10000	0	0
SMPD2	-0.071	0.15	0.2	1	-0.3	115	116
APH1B	0.027	0.004	-10000	0	-10000	0	0
APH1A	0.025	0.009	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.055	0.18	0.24	1	-0.33	115	116
PSEN1	0.027	0.005	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.04	0.007	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.099	0.2	0.24	1	-0.38	134	135
MAPK8	-0.091	0.18	0.36	5	-0.36	93	98
MAPK9	-0.09	0.18	0.43	3	-0.36	94	97
APAF1	0.027	0.004	-10000	0	-10000	0	0
NTF3	-0.063	0.19	0.21	1	-0.47	72	73
NTF4	-0.007	0.12	-10000	0	-0.47	27	27
NDN	-0.026	0.15	-10000	0	-0.47	43	43
RAC1/GDP	0.02	0.005	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.028	0.16	-10000	0	-0.27	111	111
p75 CTF/Sortilin/TRAF6/NRIF	0.061	0.027	0.24	1	-10000	0	1
RhoA-B-C/GTP	-0.057	0.18	0.23	1	-0.33	117	118
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.039	0.17	-10000	0	-0.27	126	126
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.052	0.17	0.24	1	-0.29	130	131
PRKACB	0.025	0.035	-10000	0	-0.47	2	2
proBDNF (dimer)/p75 ECD	-0.024	0.14	-10000	0	-0.34	64	64
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.005	0.11	0.33	3	-0.47	19	22
BIRC2	0.028	0.022	0.33	2	-10000	0	2
neuron projection morphogenesis	-0.093	0.16	0.2	1	-0.34	107	108
BAD	-0.098	0.18	0.38	3	-0.37	94	97
RIPK2	0.024	0.01	-10000	0	-10000	0	0
NGFR	-0.076	0.2	0.24	5	-0.47	86	91
CYCS	-0.063	0.14	0.36	1	-0.28	112	113
ADAM17	0.027	0.016	0.33	1	-10000	0	1
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.034	0.16	-10000	0	-0.3	96	96
BCL2L11	-0.097	0.18	0.38	3	-0.37	93	96
BDNF (dimer)/p75(NTR)	-0.097	0.2	0.24	1	-0.37	134	135
PI3K	-0.037	0.17	0.24	1	-0.3	107	108
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.037	0.18	0.24	1	-0.3	115	116
NDNL2	0.027	0.005	-10000	0	-10000	0	0
YWHAE	0.025	0.008	-10000	0	-10000	0	0
PRKCI	0.026	0.007	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.081	0.2	0.24	1	-0.38	116	117
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.037	0.18	0.24	1	-0.3	115	116
TRAF6	0.026	0.008	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
PRKCZ	0.024	0.043	-10000	0	-0.47	3	3
PLG	-0.005	0.03	0.21	5	-10000	0	5
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.11	0.19	0.21	1	-0.34	153	154
SQSTM1	0.026	0.007	-10000	0	-10000	0	0
NGFRAP1	0.025	0.035	-10000	0	-0.47	2	2
CASP3	-0.091	0.17	0.35	3	-0.35	94	97
E2F1	0.078	0.095	0.24	97	-10000	0	97
CASP9	0.027	0.003	-10000	0	-10000	0	0
IKK complex	-0.013	0.15	-10000	0	-0.38	37	37
NGF (dimer)/TRKA	-0.002	0.12	0.24	1	-0.34	45	46
MMP7	0.039	0.14	0.22	78	-0.47	20	98
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.026	0.17	-10000	0	-0.28	110	110
MMP3	-0.018	0.18	0.23	33	-0.47	48	81
APAF-1/Caspase 9	-0.06	0.13	-10000	0	-0.37	28	28

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.024	0.035	-10000	0	-0.47	2	2
LAT2	-0.075	0.15	-10000	0	-0.33	82	82
AP1	-0.13	0.23	-10000	0	-0.5	79	79
mol:PIP3	-0.078	0.2	0.27	14	-0.38	86	100
IKBKB	-0.052	0.14	0.23	17	-0.27	67	84
AKT1	-0.029	0.17	0.32	25	-0.37	25	50
IKBKG	-0.059	0.13	0.22	11	-0.27	71	82
MS4A2	-0.1	0.21	-10000	0	-0.46	108	108
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
MAP3K1	-0.062	0.17	0.26	9	-0.4	54	63
mol:Ca2+	-0.055	0.16	0.25	14	-0.29	86	100
LYN	0.026	0.012	-10000	0	-10000	0	0
CBLB	-0.075	0.15	-10000	0	-0.33	82	82
SHC1	0.026	0.017	0.33	1	-10000	0	1
RasGAP/p62DOK	-0.029	0.13	-10000	0	-0.26	98	98
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.018	0.06	-10000	0	-0.47	6	6
PLD2	-0.048	0.17	0.31	20	-0.28	114	134
PTPN13	-0.069	0.18	0.33	1	-0.47	35	36
PTPN11	0.018	0.023	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.032	0.14	0.33	10	-0.31	28	38
SYK	0.02	0.052	-10000	0	-0.48	4	4
GRB2	0.027	0.005	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.095	0.18	-10000	0	-0.39	89	89
LAT	-0.072	0.15	-10000	0	-0.33	80	80
PAK2	-0.072	0.19	0.26	10	-0.43	58	68
NFATC2	-0.11	0.21	-10000	0	-0.55	67	67
HRAS	-0.084	0.2	0.29	2	-0.45	66	68
GAB2	0.025	0.025	-10000	0	-0.47	1	1
PLA2G1B	0.017	0.08	-10000	0	-0.82	3	3
Fc epsilon R1	-0.075	0.19	0.22	1	-0.34	122	123
Antigen/IgE/Fc epsilon R1	-0.066	0.17	0.21	1	-0.3	122	123
mol:GDP	-0.093	0.21	0.24	1	-0.49	64	65
JUN	0.01	0.09	-10000	0	-0.47	14	14
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.024	0.026	-10000	0	-0.47	1	1
FOS	-0.12	0.23	-10000	0	-0.47	124	124
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.075	0.16	-10000	0	-0.34	83	83
CHUK	-0.061	0.13	0.22	10	-0.27	71	81
KLRG1	-0.067	0.14	-10000	0	-0.3	80	80
VAV1	-0.082	0.16	-10000	0	-0.34	89	89
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.073	0.15	-10000	0	-0.33	80	80
negative regulation of mast cell degranulation	-0.053	0.15	-10000	0	-0.35	51	51
BTK	-0.1	0.22	-10000	0	-0.54	59	59
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.095	0.2	-10000	0	-0.41	86	86
GAB2/PI3K/SHP2	-0.068	0.13	-10000	0	-0.29	71	71
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.078	0.17	-10000	0	-0.34	87	87
RAF1	0.017	0.09	-10000	0	-0.91	3	3
Fc epsilon R1/FcgammaRIIB/SHIP	-0.064	0.19	-10000	0	-0.31	129	129
FCER1G	0.029	0.059	0.23	14	-0.46	3	17
FCER1A	-0.075	0.2	0.22	1	-0.48	79	80
Antigen/IgE/Fc epsilon R1/Fyn	-0.056	0.17	-10000	0	-0.29	123	123
MAPK3	0.016	0.081	-10000	0	-0.83	3	3
MAPK1	0.016	0.081	-10000	0	-0.83	3	3
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MAPK8	-0.059	0.22	-10000	0	-0.68	36	36
DUSP1	-0.1	0.22	-10000	0	-0.47	105	105
NF-kappa-B/RelA	-0.031	0.082	-10000	0	-0.18	45	45
actin cytoskeleton reorganization	-0.071	0.18	-10000	0	-0.48	32	32
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.069	0.18	-10000	0	-0.44	52	52
FER	-0.074	0.15	-10000	0	-0.33	83	83
RELA	0.027	0.005	-10000	0	-10000	0	0
ITK	-0.061	0.14	-10000	0	-0.42	52	52
SOS1	0.027	0.005	-10000	0	-10000	0	0
PLCG1	-0.084	0.21	0.33	3	-0.48	62	65
cytokine secretion	-0.027	0.055	-10000	0	-0.16	6	6
SPHK1	-0.076	0.15	-10000	0	-0.33	80	80
PTK2	-0.075	0.18	-10000	0	-0.51	30	30
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.098	0.2	-10000	0	-0.4	89	89
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.078	0.2	0.29	8	-0.42	62	70
MAP2K2	0.012	0.082	-10000	0	-0.85	3	3
MAP2K1	0.012	0.082	-10000	0	-0.85	3	3
MAP2K7	0.027	0.005	-10000	0	-10000	0	0
KLRG1/SHP2	-0.057	0.13	-10000	0	-0.32	50	50
MAP2K4	-0.071	0.3	-10000	0	-0.9	46	46
Fc epsilon R1/FcgammaRIIB	-0.072	0.19	-10000	0	-0.33	130	130
mol:Choline	-0.047	0.17	0.3	20	-0.28	114	134
SHC/Grb2/SOS1	-0.039	0.16	-10000	0	-0.37	47	47
FYN	0.022	0.043	-10000	0	-0.47	3	3
DOK1	0.027	0.011	0.21	1	-10000	0	1
PXN	-0.067	0.18	0.33	1	-0.48	30	31
HCLS1	-0.074	0.15	-10000	0	-0.33	82	82
PRKCB	-0.088	0.18	0.26	9	-0.35	86	95
FCGR2B	-0.004	0.12	0.25	3	-0.47	24	27
IGHE	0	0.008	-10000	0	-10000	0	0
KLRG1/SHIP	-0.054	0.15	-10000	0	-0.36	51	51
LCP2	0.022	0.043	-10000	0	-0.47	3	3
PLA2G4A	-0.085	0.16	-10000	0	-0.35	89	89
RASA1	0.027	0.006	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.047	0.17	0.3	20	-0.28	114	134
IKK complex	-0.033	0.11	0.23	18	-0.21	57	75
WIPF1	0.012	0.084	-10000	0	-0.47	12	12

×

Glypican 2 network

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
MDK	0.037	0.047	0.22	23	-9999	23
GPC2	0.093	0.092	0.22	139	-9999	139
GPC2/Midkine	0.088	0.076	0.29	19	-9999	19
neuron projection morphogenesis	0.088	0.076	0.29	19	-9999	19

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.027	0.057	0.22	22	-0.44	1	23
CDKN2C	0.027	0.026	0.23	2	-10000	0	2
CDKN2A	0.11	0.1	0.22	187	-10000	0	187
CCND2	-0.023	0.065	0.2	1	-0.23	20	21
RB1	0.016	0.073	0.32	10	-0.22	12	22
CDK4	-0.021	0.061	0.2	1	-0.36	9	10
CDK6	-0.025	0.069	0.21	1	-0.31	14	15
G1/S progression	0.027	0.11	0.18	112	-0.35	10	122

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	0.009	0.12	-10000	0	-0.25	67	67
ER alpha/Gai/GDP/Gbeta gamma	-0.2	0.31	-10000	0	-0.61	117	117
AKT1	-0.16	0.36	-10000	0	-0.86	82	82
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.16	0.37	-10000	0	-0.88	82	82
mol:Ca2+	-0.053	0.16	-10000	0	-0.39	64	64
IGF1R	0.025	0.035	-10000	0	-0.47	2	2
E2/ER alpha (dimer)/Striatin	-0.017	0.12	-10000	0	-0.28	65	65
SHC1	0.026	0.017	0.33	1	-10000	0	1
apoptosis	0.15	0.34	0.81	82	-10000	0	82
RhoA/GTP	-0.013	0.084	-10000	0	-0.22	56	56
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.14	0.26	-10000	0	-0.51	112	112
regulation of stress fiber formation	0.025	0.08	0.3	3	-0.24	2	5
E2/ERA-ERB (dimer)	-0.017	0.12	-10000	0	-0.28	66	66
KRAS	0.027	0.016	0.33	1	-10000	0	1
G13/GTP	-0.014	0.11	-10000	0	-0.26	64	64
pseudopodium formation	-0.025	0.08	0.24	2	-0.3	3	5
E2/ER alpha (dimer)/PELP1	-0.019	0.12	-10000	0	-0.28	65	65
GRB2	0.027	0.005	-10000	0	-10000	0	0
GNG2	0.02	0.06	-10000	0	-0.47	6	6
GNAO1	-0.12	0.23	-10000	0	-0.47	124	124
HRAS	0.025	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.14	0.28	-10000	0	-0.64	86	86
E2/ER beta (dimer)	0.021	0.01	0.15	2	-10000	0	2
mol:GDP	-0.043	0.14	-10000	0	-0.34	70	70
mol:NADP	-0.14	0.28	-10000	0	-0.64	86	86
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
mol:IP3	-0.064	0.16	-10000	0	-0.4	64	64
IGF-1R heterotetramer	0.025	0.035	-10000	0	-0.47	2	2
PLCB1	-0.059	0.16	-10000	0	-0.42	60	60
PLCB2	-0.057	0.16	-10000	0	-0.41	62	62
IGF1	-0.19	0.24	-10000	0	-0.47	176	176
mol:L-citrulline	-0.14	0.28	-10000	0	-0.64	86	86
RHOA	0.026	0.006	-10000	0	-10000	0	0
Gai/GDP	-0.27	0.4	-10000	0	-0.78	145	145
JNK cascade	0.021	0.01	0.15	2	-10000	0	2
BCAR1	0.026	0.006	-10000	0	-10000	0	0
ESR2	0.028	0.014	0.21	2	-10000	0	2
GNAQ	0.025	0.009	-10000	0	-10000	0	0
ESR1	-0.054	0.18	-10000	0	-0.47	66	66
Gq family/GDP/Gbeta gamma	-0.023	0.16	-10000	0	-0.71	16	16
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.018	0.11	-10000	0	-0.39	4	4
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.13	0.26	-10000	0	-0.5	110	110
GNAZ	-0.08	0.2	-10000	0	-0.47	87	87
E2/ER alpha (dimer)	-0.038	0.13	-10000	0	-0.33	66	66
STRN	0.027	0.005	-10000	0	-10000	0	0
GNAL	-0.17	0.24	-10000	0	-0.47	163	163
PELP1	0.025	0.008	-10000	0	-10000	0	0
MAPK11	0.014	0.006	-10000	0	-10000	0	0
GNAI2	0.026	0.006	-10000	0	-10000	0	0
GNAI3	0.028	0.003	-10000	0	-10000	0	0
GNAI1	0.024	0.043	-10000	0	-0.47	3	3
HBEGF	-0.17	0.29	0.35	10	-0.56	113	123
cAMP biosynthetic process	-0.11	0.16	-10000	0	-0.27	189	189
SRC	-0.18	0.29	0.35	1	-0.57	115	116
PI3K	0.035	0.023	-10000	0	-0.34	1	1
GNB1	0.027	0.003	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.015	0.14	-10000	0	-0.34	53	53
SOS1	0.027	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.18	0.23	-10000	0	-0.46	144	144
Gs family/GTP	-0.11	0.17	-10000	0	-0.28	189	189
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.046	0.021	0.22	1	-10000	0	1
vasodilation	-0.14	0.26	-10000	0	-0.6	86	86
mol:DAG	-0.064	0.16	-10000	0	-0.4	64	64
Gs family/GDP/Gbeta gamma	-0.11	0.17	-10000	0	-0.4	74	74
MSN	-0.027	0.085	0.24	2	-0.33	3	5
Gq family/GTP	-0.052	0.17	-10000	0	-0.44	59	59
mol:PI-3-4-5-P3	-0.15	0.35	-10000	0	-0.84	82	82
NRAS	0.028	0.002	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.14	0.26	0.6	86	-10000	0	86
GRB2/SOS1	0.039	0.01	-10000	0	-10000	0	0
RhoA/GDP	-0.028	0.14	-10000	0	-0.33	67	67
NOS3	-0.15	0.3	-10000	0	-0.68	86	86
GNA11	0.026	0.025	-10000	0	-0.47	1	1
MAPKKK cascade	-0.12	0.28	-10000	0	-0.66	81	81
E2/ER alpha (dimer)/PELP1/Src	-0.15	0.27	0.27	1	-0.53	113	114
ruffle organization	-0.025	0.08	0.24	2	-0.3	3	5
ROCK2	-0.012	0.094	0.34	2	-0.25	6	8
GNA14	-0.03	0.16	-10000	0	-0.47	45	45
GNA15	0.023	0.043	-10000	0	-0.47	3	3
GNA13	0.027	0.005	-10000	0	-10000	0	0
MMP9	-0.16	0.28	0.4	10	-0.55	111	121
MMP2	-0.18	0.29	0.3	3	-0.55	122	125

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.019	0.12	-10000	0	-0.29	64	64
EFNA5	0.011	0.088	0.21	1	-0.47	13	14
FYN	-0.031	0.11	0.19	4	-0.26	67	71
neuron projection morphogenesis	-0.019	0.12	-10000	0	-0.29	64	64
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	-0.019	0.12	-10000	0	-0.29	64	64
EPHA5	-0.057	0.16	0.21	2	-0.47	53	55

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.029	0.23	0.27	19	-0.47	70	89
FYN	-0.078	0.3	0.29	12	-0.64	74	86
LAT/GRAP2/SLP76	-0.053	0.25	0.26	7	-0.51	76	83
IKBKB	0.025	0.009	-10000	0	-10000	0	0
AKT1	-0.046	0.2	0.25	11	-0.41	76	87
B2M	0.026	0.01	-10000	0	-10000	0	0
IKBKG	-0.005	0.059	0.12	8	-0.13	48	56
MAP3K8	0.024	0.035	-10000	0	-0.47	2	2
mol:Ca2+	-0.019	0.023	0.083	3	-0.063	38	41
integrin-mediated signaling pathway	0.033	0.032	-10000	0	-0.28	4	4
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.079	0.29	0.31	8	-0.6	78	86
TRPV6	-0.043	0.19	0.98	6	-0.46	40	46
CD28	0.008	0.099	0.21	2	-0.47	16	18
SHC1	-0.065	0.28	0.28	21	-0.57	78	99
receptor internalization	-0.087	0.29	0.2	3	-0.57	86	89
PRF1	-0.089	0.34	-10000	0	-0.88	48	48
KRAS	0.027	0.016	0.33	1	-10000	0	1
GRB2	0.027	0.005	-10000	0	-10000	0	0
COT/AKT1	-0.024	0.16	0.26	8	-0.34	65	73
LAT	-0.071	0.28	0.26	9	-0.57	79	88
EntrezGene:6955	0	0.003	-10000	0	-10000	0	0
CD3D	-0.012	0.14	0.22	3	-0.47	32	35
CD3E	-0.021	0.15	-10000	0	-0.48	39	39
CD3G	-0.026	0.15	-10000	0	-0.47	42	42
RASGRP2	-0.038	0.079	0.081	1	-0.17	102	103
RASGRP1	-0.035	0.2	0.25	12	-0.42	69	81
HLA-A	0	0.005	-10000	0	-10000	0	0
RASSF5	0.022	0.049	-10000	0	-0.47	4	4
RAP1A/GTP/RAPL	0.033	0.032	-10000	0	-0.28	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.007	0.073	0.14	26	-0.13	50	76
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.033	0.081	-10000	0	-0.21	58	58
PRKCA	-0.018	0.12	0.17	16	-0.27	59	75
GRAP2	-0.026	0.15	-10000	0	-0.47	43	43
mol:IP3	-0.042	0.18	0.22	35	-0.4	70	105
EntrezGene:6957	0	0.004	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.08	0.26	-10000	0	-0.66	58	58
ORAI1	0.022	0.13	0.4	2	-0.8	6	8
CSK	-0.077	0.28	0.26	8	-0.59	78	86
B7 family/CD28	-0.033	0.29	0.29	8	-0.62	64	72
CHUK	0.027	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.1	0.32	-10000	0	-0.66	80	80
PTPN6	-0.079	0.28	0.24	11	-0.57	80	91
VAV1	-0.081	0.29	0.26	8	-0.6	78	86
Monovalent TCR/CD3	-0.056	0.21	-10000	0	-0.47	64	64
CBL	0.026	0.007	-10000	0	-10000	0	0
LCK	-0.079	0.3	0.28	11	-0.66	70	81
PAG1	-0.07	0.28	0.26	12	-0.58	78	90
RAP1A	0.028	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.099	0.32	-10000	0	-0.64	81	81
CD80	0.05	0.065	0.21	54	-10000	0	54
CD86	0.022	0.051	0.21	1	-0.47	4	5
PDK1/CARD11/BCL10/MALT1	-0.029	0.1	-10000	0	-0.25	60	60
HRAS	0.025	0.008	-10000	0	-10000	0	0
GO:0035030	-0.056	0.22	0.24	6	-0.51	64	70
CD8A	-0.02	0.15	0.22	1	-0.48	39	40
CD8B	-0.013	0.14	0.22	7	-0.48	35	42
PTPRC	-0.026	0.16	0.21	2	-0.47	44	46
PDK1/PKC theta	-0.053	0.24	0.28	11	-0.51	74	85
CSK/PAG1	-0.063	0.28	0.28	16	-0.56	76	92
SOS1	0.027	0.005	-10000	0	-10000	0	0
peptide-MHC class I	0.019	0.013	-10000	0	-10000	0	0
GRAP2/SLP76	-0.07	0.29	0.27	5	-0.58	82	87
STIM1	0.008	0.044	-10000	0	-10000	0	0
RAS family/GTP	0.015	0.095	0.19	16	-0.18	42	58
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.096	0.31	0.2	3	-0.62	86	89
mol:DAG	-0.057	0.15	0.11	6	-0.35	72	78
RAP1A/GDP	0.006	0.035	0.076	13	-0.064	31	44
PLCG1	0.026	0.007	-10000	0	-10000	0	0
CD247	0.018	0.062	0.21	1	-0.47	6	7
cytotoxic T cell degranulation	-0.082	0.31	-10000	0	-0.82	49	49
RAP1A/GTP	-0.015	0.029	-10000	0	-0.064	102	102
mol:PI-3-4-5-P3	-0.057	0.23	0.28	11	-0.49	75	86
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.052	0.24	0.24	35	-0.52	70	105
NRAS	0.028	0.002	-10000	0	-10000	0	0
ZAP70	0.01	0.091	0.21	1	-0.47	14	15
GRB2/SOS1	0.039	0.01	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.063	0.23	-10000	0	-0.52	71	71
MALT1	0.026	0.007	-10000	0	-10000	0	0
TRAF6	0.026	0.008	-10000	0	-10000	0	0
CD8 heterodimer	-0.02	0.18	0.32	1	-0.45	53	54
CARD11	0.022	0.066	0.3	4	-0.47	6	10
PRKCB	-0.056	0.15	0.16	8	-0.3	86	94
PRKCE	-0.017	0.12	0.17	15	-0.27	59	74
PRKCQ	-0.067	0.28	0.29	10	-0.57	79	89
LCP2	0.022	0.043	-10000	0	-0.47	3	3
BCL10	0.027	0.004	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.035	0.17	0.24	11	-0.35	73	84
IKK complex	0.001	0.069	0.16	19	-0.12	44	63
RAS family/GDP	-0.005	0.013	-10000	0	-10000	0	0
MAP3K14	-0.017	0.12	0.21	10	-0.26	63	73
PDPK1	-0.041	0.19	0.26	9	-0.39	73	82
TCR/CD3/MHC I/CD8/Fyn	-0.12	0.35	-10000	0	-0.74	79	79

×

S1P4 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	-0.12	0.23	-10000	0	-0.47	124	124
CDC42/GTP	-0.085	0.17	-10000	0	-0.31	120	120
PLCG1	-0.092	0.16	-10000	0	-0.32	115	115
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.026	0.006	-10000	0	-10000	0	0
GNAI3	0.028	0.003	-10000	0	-10000	0	0
G12/G13	0.037	0.012	-10000	0	-10000	0	0
cell migration	-0.084	0.16	-10000	0	-0.3	120	120
S1PR5	0.031	0.051	0.23	13	-0.47	2	15
S1PR4	0.025	0.046	0.21	3	-0.47	3	6
MAPK3	-0.093	0.16	-10000	0	-0.31	118	118
MAPK1	-0.095	0.17	-10000	0	-0.32	119	119
S1P/S1P5/Gi	-0.093	0.18	-10000	0	-0.3	148	148
GNAI1	0.024	0.043	-10000	0	-0.47	3	3
CDC42/GDP	0.02	0.002	-10000	0	-10000	0	0
S1P/S1P5/G12	0.036	0.031	-10000	0	-0.28	2	2
RHOA	0.026	0.053	0.2	29	-0.24	2	31
S1P/S1P4/Gi	-0.097	0.18	-10000	0	-0.3	152	152
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	-0.08	0.2	-10000	0	-0.47	87	87
S1P/S1P4/G12/G13	0.046	0.03	-10000	0	-0.26	2	2
GNA12	0.026	0.007	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
CDC42	0.028	0.003	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR 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
ERK1-2/ELK1	-0.12	0.22	-10000	0	-0.41	106	106
MAP3K8	0.021	0.036	-10000	0	-0.47	2	2
FOS	-0.086	0.17	-10000	0	-0.4	63	63
PRKCA	0.011	0.052	-10000	0	-0.47	4	4
PTPN7	0.007	0.067	0.21	2	-0.47	6	8
HRAS	0.024	0.008	-10000	0	-10000	0	0
PRKCB	-0.12	0.22	-10000	0	-0.47	112	112
NRAS	0.027	0.002	-10000	0	-10000	0	0
RAS family/GTP	0.037	0.026	0.19	1	-10000	0	1
MAPK3	-0.044	0.13	-10000	0	-0.55	14	14
MAP2K1	-0.1	0.2	-10000	0	-0.4	116	116
ELK1	0.01	0.027	-10000	0	-10000	0	0
BRAF	-0.1	0.19	-10000	0	-0.39	113	113
mol:GTP	-0.001	0.002	-10000	0	-0.005	128	128
MAPK1	-0.046	0.13	-10000	0	-0.54	16	16
RAF1	-0.094	0.18	0.22	1	-0.39	105	106
KRAS	0.026	0.016	0.33	1	-10000	0	1

×

LPA receptor mediated 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
GNB1/GNG2	0.005	0.12	-10000	0	-0.27	55	55
NF kappa B1 p50/RelA/I kappa B alpha	-0.019	0.11	0.3	1	-0.33	12	13
AP1	-0.1	0.19	-10000	0	-0.31	151	151
mol:PIP3	-0.037	0.11	-10000	0	-0.33	31	31
AKT1	-0.002	0.097	0.29	2	-0.34	7	9
PTK2B	-0.055	0.12	0.2	2	-0.33	43	45
RHOA	-0.004	0.067	0.28	1	-0.27	13	14
PIK3CB	0.026	0.006	-10000	0	-10000	0	0
mol:Ca2+	-0.021	0.083	0.23	4	-0.28	11	15
MAGI3	0.028	0.003	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
apoptosis	-0.04	0.13	0.19	1	-0.28	79	80
HRAS/GDP	0.019	0.006	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.059	0.13	0.29	2	-0.35	37	39
NF kappa B1 p50/RelA	-0.037	0.12	-10000	0	-0.34	28	28
endothelial cell migration	-0.046	0.17	-10000	0	-0.45	56	56
ADCY4	-0.13	0.21	-10000	0	-0.41	114	114
ADCY5	-0.24	0.28	-10000	0	-0.53	163	163
ADCY6	-0.13	0.2	-10000	0	-0.41	112	112
ADCY7	-0.13	0.2	-10000	0	-0.41	111	111
ADCY1	-0.12	0.2	-10000	0	-0.41	111	111
ADCY2	-0.2	0.26	-10000	0	-0.48	152	152
ADCY3	-0.12	0.2	-10000	0	-0.41	112	112
ADCY8	-0.12	0.2	-10000	0	-0.41	108	108
ADCY9	-0.13	0.22	-10000	0	-0.43	114	114
GSK3B	-0.049	0.12	0.2	7	-0.35	31	38
arachidonic acid secretion	-0.14	0.21	-10000	0	-0.43	117	117
GNG2	0.02	0.06	-10000	0	-0.47	6	6
TRIP6	0.019	0.017	-10000	0	-10000	0	0
GNAO1	-0.11	0.18	-10000	0	-0.32	150	150
HRAS	0.025	0.008	-10000	0	-10000	0	0
NFKBIA	-0.038	0.11	0.3	1	-0.33	20	21
GAB1	0.026	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.02	0.16	-10000	0	-0.83	13	13
JUN	0.01	0.091	-10000	0	-0.47	14	14
LPA/LPA2/NHERF2	0.028	0.034	-10000	0	-10000	0	0
TIAM1	0.001	0.18	-10000	0	-0.97	13	13
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
mol:IP3	-0.021	0.083	0.23	4	-0.28	13	17
PLCB3	0.013	0.03	0.2	3	-10000	0	3
FOS	-0.12	0.23	-10000	0	-0.47	124	124
positive regulation of mitosis	-0.14	0.21	-10000	0	-0.43	117	117
LPA/LPA1-2-3	-0.015	0.14	0.23	1	-0.28	76	77
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.026	0.006	-10000	0	-10000	0	0
stress fiber formation	-0.035	0.12	0.29	1	-0.34	30	31
GNAZ	-0.083	0.16	-10000	0	-0.31	124	124
EGFR/PI3K-beta/Gab1	-0.03	0.12	-10000	0	-0.34	31	31
positive regulation of dendritic cell cytokine production	-0.016	0.14	0.22	1	-0.28	76	77
LPA/LPA2/MAGI-3	0.029	0.034	-10000	0	-10000	0	0
ARHGEF1	-0.001	0.11	0.2	29	-0.25	46	75
GNAI2	-0.023	0.11	-10000	0	-0.28	56	56
GNAI3	-0.023	0.11	-10000	0	-0.28	57	57
GNAI1	-0.024	0.11	-10000	0	-0.28	59	59
LPA/LPA3	-0.016	0.1	0.15	3	-0.3	39	42
LPA/LPA2	0.013	0.034	0.15	1	-0.11	23	24
LPA/LPA1	-0.026	0.13	-10000	0	-0.33	58	58
HB-EGF/EGFR	0.021	0.094	0.26	12	-0.33	21	33
HBEGF	0.01	0.085	0.3	6	-0.38	14	20
mol:DAG	-0.021	0.083	0.23	4	-0.28	13	17
cAMP biosynthetic process	-0.16	0.23	0.29	1	-0.43	139	140
NFKB1	0.027	0.004	-10000	0	-10000	0	0
SRC	0.026	0.007	-10000	0	-10000	0	0
GNB1	0.027	0.003	-10000	0	-10000	0	0
LYN	-0.029	0.11	0.27	3	-0.3	32	35
GNAQ	-0.011	0.079	0.19	1	-0.26	33	34
LPAR2	0.029	0.023	0.29	3	-10000	0	3
LPAR3	-0.012	0.14	0.24	5	-0.47	33	38
LPAR1	-0.022	0.14	-10000	0	-0.35	53	53
IL8	-0.097	0.22	0.3	2	-0.5	75	77
PTK2	-0.029	0.12	0.21	9	-0.27	66	75
Rac1/GDP	0.02	0.005	-10000	0	-10000	0	0
CASP3	-0.04	0.13	0.19	1	-0.28	79	80
EGFR	0.021	0.085	0.33	8	-0.47	9	17
PLCG1	-0.021	0.093	0.21	6	-0.26	40	46
PLD2	-0.033	0.12	0.21	8	-0.27	71	79
G12/G13	0.007	0.11	-10000	0	-0.26	51	51
PI3K-beta	-0.021	0.093	-10000	0	-0.31	17	17
cell migration	0.002	0.074	0.2	2	-0.26	12	14
SLC9A3R2	0.027	0.006	-10000	0	-10000	0	0
PXN	-0.036	0.12	0.29	1	-0.34	30	31
HRAS/GTP	-0.14	0.22	-10000	0	-0.44	116	116
RAC1	0.026	0.006	-10000	0	-10000	0	0
MMP9	0.068	0.1	0.22	102	-0.47	5	107
PRKCE	0.027	0.006	-10000	0	-10000	0	0
PRKCD	-0.022	0.084	0.31	1	-0.31	7	8
Gi(beta/gamma)	-0.12	0.2	-10000	0	-0.4	108	108
mol:LPA	-0.01	0.044	-10000	0	-0.16	28	28
TRIP6/p130 Cas/FAK1/Paxillin	-0.021	0.13	0.3	1	-0.4	20	21
MAPKKK cascade	-0.14	0.21	-10000	0	-0.43	117	117
contractile ring contraction involved in cytokinesis	-0.004	0.069	0.28	1	-0.27	13	14
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.041	0.12	0.19	1	-0.27	75	76
GNA15	-0.01	0.081	0.19	1	-0.26	35	36
GNA12	0.026	0.007	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
MAPT	-0.061	0.13	0.29	2	-0.36	37	39
GNA11	-0.009	0.081	0.19	1	-0.27	32	33
Rac1/GTP	0.02	0.16	-10000	0	-0.88	13	13
MMP2	-0.046	0.17	-10000	0	-0.45	56	56

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.21	0.58	-10000	0	-1.2	78	78
IL23A	-0.16	0.5	-10000	0	-1.1	64	64
NF kappa B1 p50/RelA/I kappa B alpha	-0.16	0.5	-10000	0	-1.1	71	71
positive regulation of T cell mediated cytotoxicity	-0.2	0.57	-10000	0	-1.2	78	78
ITGA3	-0.16	0.49	-10000	0	-1.1	66	66
IL17F	-0.1	0.34	-10000	0	-0.68	70	70
IL12B	0.021	0.072	0.27	12	-10000	0	12
STAT1 (dimer)	-0.19	0.54	-10000	0	-1.1	78	78
CD4	-0.16	0.49	-10000	0	-1.1	68	68
IL23	-0.16	0.48	-10000	0	-1.1	59	59
IL23R	0.014	0.11	-10000	0	-0.88	1	1
IL1B	-0.18	0.54	-10000	0	-1.2	69	69
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.16	0.49	-10000	0	-1.1	67	67
TYK2	0.013	0.044	-10000	0	-10000	0	0
STAT4	0.002	0.11	-10000	0	-0.47	20	20
STAT3	0.027	0.005	-10000	0	-10000	0	0
IL18RAP	0.004	0.11	-10000	0	-0.46	20	20
IL12RB1	0.011	0.1	0.25	20	-0.5	10	30
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.022	0.089	0.21	17	-0.37	9	26
IL23R/JAK2	0.026	0.14	-10000	0	-0.79	1	1
positive regulation of chronic inflammatory response	-0.2	0.57	-10000	0	-1.2	78	78
natural killer cell activation	0	0.009	-10000	0	-10000	0	0
JAK2	0.018	0.055	-10000	0	-10000	0	0
PIK3R1	0.025	0.026	-10000	0	-0.47	1	1
NFKB1	0.028	0.006	-10000	0	-10000	0	0
RELA	0.027	0.006	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.14	0.46	-10000	0	-1	59	59
ALOX12B	-0.16	0.49	-10000	0	-1	69	69
CXCL1	-0.21	0.56	-10000	0	-1.2	81	81
T cell proliferation	-0.2	0.57	-10000	0	-1.2	78	78
NFKBIA	0.027	0.007	-10000	0	-10000	0	0
IL17A	-0.054	0.29	-10000	0	-0.54	62	62
PI3K	-0.18	0.52	-10000	0	-1.1	74	74
IFNG	0.008	0.038	0.1	5	-0.11	8	13
STAT3 (dimer)	-0.16	0.49	-10000	0	-1.1	69	69
IL18R1	0.026	0.035	-10000	0	-0.46	2	2
IL23/IL23R/JAK2/TYK2/SOCS3	-0.097	0.36	-10000	0	-0.68	77	77
IL18/IL18R	0.037	0.09	-10000	0	-0.29	26	26
macrophage activation	-0.008	0.023	0.043	2	-0.043	59	61
TNF	-0.17	0.51	-10000	0	-1.1	66	66
STAT3/STAT4	-0.19	0.53	-10000	0	-1.1	75	75
STAT4 (dimer)	-0.2	0.55	-10000	0	-1.2	77	77
IL18	0.02	0.06	-10000	0	-0.46	6	6
IL19	-0.16	0.49	-10000	0	-1.1	67	67
STAT5A (dimer)	-0.19	0.54	-10000	0	-1.1	75	75
STAT1	0.029	0.019	0.21	4	-10000	0	4
SOCS3	-0.021	0.15	-10000	0	-0.47	39	39
CXCL9	-0.17	0.52	-10000	0	-1.1	72	72
MPO	-0.16	0.49	-10000	0	-1	68	68
positive regulation of humoral immune response	-0.2	0.57	-10000	0	-1.2	78	78
IL23/IL23R/JAK2/TYK2	-0.22	0.61	-10000	0	-1.3	75	75
IL6	-0.47	0.73	-10000	0	-1.2	191	191
STAT5A	0.026	0.025	-10000	0	-0.47	1	1
IL2	0.015	0.021	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0.009	-10000	0	-10000	0	0
CD3E	-0.21	0.57	-10000	0	-1.2	79	79
keratinocyte proliferation	-0.2	0.57	-10000	0	-1.2	78	78
NOS2	-0.17	0.5	-10000	0	-1.1	69	69

×

S1P5 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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.078	0.16	0.3	117	-10000	0	117
GNAI2	0.026	0.006	-10000	0	-10000	0	0
S1P/S1P5/G12	0.036	0.031	-10000	0	-0.28	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.12	0.23	-10000	0	-0.47	124	124
RhoA/GTP	-0.08	0.17	-10000	0	-0.3	117	117
negative regulation of cAMP metabolic process	-0.093	0.17	-10000	0	-0.3	148	148
GNAZ	-0.08	0.2	-10000	0	-0.47	87	87
GNAI3	0.028	0.003	-10000	0	-10000	0	0
GNA12	0.026	0.007	-10000	0	-10000	0	0
S1PR5	0.031	0.051	0.23	13	-0.47	2	15
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.093	0.18	-10000	0	-0.3	148	148
RhoA/GDP	0.02	0.005	-10000	0	-10000	0	0
RHOA	0.026	0.006	-10000	0	-10000	0	0
GNAI1	0.024	0.043	-10000	0	-0.47	3	3

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.038	0.021	-10000	0	-0.34	1	1
alphaV beta3 Integrin	-0.083	0.2	-10000	0	-0.35	132	132
PTK2	-0.08	0.21	0.32	7	-0.5	52	59
IGF1R	0.025	0.035	-10000	0	-0.47	2	2
PI4KB	0.024	0.009	-10000	0	-10000	0	0
MFGE8	0.025	0.035	-10000	0	-0.47	2	2
SRC	0.026	0.007	-10000	0	-10000	0	0
CDKN1B	-0.1	0.23	-10000	0	-0.62	61	61
VEGFA	0.027	0.005	-10000	0	-10000	0	0
ILK	-0.12	0.24	-10000	0	-0.6	72	72
ROCK1	0.027	0.006	-10000	0	-10000	0	0
AKT1	-0.11	0.23	-10000	0	-0.56	73	73
PTK2B	-0.006	0.091	0.36	1	-0.25	41	42
alphaV/beta3 Integrin/JAM-A	-0.09	0.2	0.28	1	-0.35	136	137
CBL	0.026	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.014	0.11	-10000	0	-0.29	44	44
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.08	0.17	-10000	0	-0.27	176	176
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.028	0.11	-10000	0	-0.37	23	23
alphaV/beta3 Integrin/Syndecan-1	0.011	0.11	-10000	0	-0.28	46	46
PI4KA	0.027	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.16	0.26	-10000	0	-0.4	194	194
PI4 Kinase	0.035	0.015	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	0.057	0.14	-10000	0	-0.29	43	43
RPS6KB1	-0.18	0.22	-10000	0	-0.47	119	119
TLN1	0.025	0.009	-10000	0	-10000	0	0
MAPK3	-0.23	0.33	-10000	0	-0.65	142	142
GPR124	-0.016	0.13	-10000	0	-0.47	32	32
MAPK1	-0.23	0.34	-10000	0	-0.65	143	143
PXN	0.027	0.004	-10000	0	-10000	0	0
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
alphaV/beta3 Integrin/Tumstatin	-0.069	0.18	-10000	0	-0.32	129	129
cell adhesion	0.009	0.1	-10000	0	-0.28	42	42
ANGPTL3	0.018	0.03	0.21	5	-10000	0	5
VEGFR2 homodimer/VEGFA homodimer/Src	0.049	0.026	-10000	0	-0.28	1	1
IGF-1R heterotetramer	0.025	0.035	-10000	0	-0.47	2	2
Rac1/GDP	0.02	0.005	-10000	0	-10000	0	0
TGFBR2	0.024	0.035	-10000	0	-0.47	2	2
ITGB3	-0.027	0.15	-10000	0	-0.47	44	44
IGF1	-0.19	0.24	-10000	0	-0.47	176	176
RAC1	0.026	0.006	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	-0.014	0.14	-10000	0	-0.35	55	55
apoptosis	0.027	0.006	-10000	0	-10000	0	0
CD47	0.027	0.006	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.015	0.1	-10000	0	-0.28	41	41
VCL	0.027	0.006	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.027	0.17	-10000	0	-0.36	76	76
CSF1	0.009	0.094	-10000	0	-0.47	15	15
PIK3C2A	-0.12	0.24	-10000	0	-0.6	71	71
PI4 Kinase/Pyk2	-0.084	0.17	-10000	0	-0.41	61	61
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.028	0.1	-10000	0	-0.27	41	41
FAK1/Vinculin	-0.052	0.18	0.32	9	-0.4	49	58
alphaV beta3/Integrin/ppsTEM5	-0.013	0.14	-10000	0	-0.35	55	55
RHOA	0.026	0.006	-10000	0	-10000	0	0
VTN	-0.045	0.18	0.21	7	-0.47	60	67
BCAR1	0.026	0.006	-10000	0	-10000	0	0
FGF2	-0.13	0.23	-10000	0	-0.47	127	127
F11R	-0.077	0.15	-10000	0	-0.34	102	102
alphaV/beta3 Integrin/Lactadherin	0.014	0.11	-10000	0	-0.28	45	45
alphaV/beta3 Integrin/TGFBR2	0.014	0.11	-10000	0	-0.29	41	41
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.049	0.065	-10000	0	-0.26	15	15
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.014	0.093	-10000	0	-0.26	41	41
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.025	0.094	0.21	26	-0.47	11	37
alphaV/beta3 Integrin/Pyk2	0.013	0.094	-10000	0	-0.25	41	41
SDC1	0.019	0.06	-10000	0	-0.47	6	6
VAV3	0.012	0.07	0.34	3	-0.24	18	21
PTPN11	0.027	0.005	-10000	0	-10000	0	0
IRS1	0.017	0.065	-10000	0	-0.47	7	7
FAK1/Paxillin	-0.052	0.18	0.33	8	-0.4	50	58
cell migration	-0.048	0.16	0.28	15	-0.36	48	63
ITGAV	0.027	0.006	-10000	0	-10000	0	0
PI3K	-0.073	0.19	0.25	1	-0.32	128	129
SPP1	0.1	0.091	0.21	161	-10000	0	161
KDR	0.025	0.035	-10000	0	-0.47	2	2
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.027	0.006	-10000	0	-10000	0	0
COL4A3	-0.1	0.21	0.21	4	-0.47	102	106
angiogenesis	-0.21	0.35	0.29	2	-0.65	141	143
Rac1/GTP	0.023	0.062	0.28	1	-0.22	18	19
EDIL3	-0.041	0.17	-10000	0	-0.47	55	55
cell proliferation	0.014	0.1	-10000	0	-0.29	41	41

×

Calcium signaling in the CD4+ TCR pathway

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
NFATC1	-0.012	0.07	-10000	0	-0.31	18	18
NFATC2	-0.047	0.11	-10000	0	-0.3	65	65
NFATC3	-0.001	0.028	-10000	0	-10000	0	0
CD40LG	-0.18	0.26	-10000	0	-0.54	110	110
PTGS2	-0.2	0.28	-10000	0	-0.56	131	131
JUNB	0.021	0.055	-10000	0	-0.47	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	0.008	0.023	-10000	0	-10000	0	0
CaM/Ca2+	0.008	0.023	-10000	0	-10000	0	0
CALM1	0.02	0.018	-10000	0	-10000	0	0
JUN	0.004	0.092	-10000	0	-0.48	14	14
mol:Ca2+	-0.004	0.008	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.016	0.008	-10000	0	-10000	0	0
FOSL1	-0.006	0.12	-10000	0	-0.47	27	27
CREM	0.026	0.006	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.05	0.18	-10000	0	-0.39	53	53
FOS	-0.13	0.23	-10000	0	-0.47	124	124
IFNG	-0.14	0.24	-10000	0	-0.48	100	100
AP-1/NFAT1-c-4	-0.15	0.3	-10000	0	-0.57	102	102
FASLG	-0.16	0.24	-10000	0	-0.5	101	101
NFAT1-c-4/ICER1	-0.047	0.13	-10000	0	-0.3	67	67
IL2RA	-0.16	0.25	-10000	0	-0.52	97	97
FKBP12/FK506	0.02	0.005	-10000	0	-10000	0	0
CSF2	-0.15	0.24	0.29	1	-0.49	101	102
JunB/Fra1/NFAT1-c-4	-0.051	0.16	-10000	0	-0.33	63	63
IL4	-0.16	0.23	-10000	0	-0.49	101	101
IL2	-0.01	0.14	-10000	0	-0.95	8	8
IL3	-0.018	0.13	-10000	0	-0.72	13	13
FKBP1A	0.026	0.006	-10000	0	-10000	0	0
BATF3	0.023	0.058	0.21	4	-0.47	5	9
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.025	0.009	-10000	0	-10000	0	0

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.03	0.029	-10000	0	-0.34	1	1
PDGFRB	0.013	0.074	-10000	0	-0.47	9	9
SPHK1	0.001	0.084	-10000	0	-0.85	2	2
mol:S1P	-0.006	0.086	0.31	2	-0.76	2	4
S1P1/S1P/Gi	-0.19	0.26	-10000	0	-0.44	171	171
GNAO1	-0.13	0.23	-10000	0	-0.47	124	124
PDGFB-D/PDGFRB/PLCgamma1	-0.15	0.24	0.28	3	-0.44	135	138
PLCG1	-0.17	0.24	0.3	1	-0.45	140	141
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.013	0.074	-10000	0	-0.47	9	9
GNAI2	0.016	0.02	-10000	0	-10000	0	0
GNAI3	0.018	0.019	-10000	0	-10000	0	0
GNAI1	0.015	0.046	-10000	0	-0.48	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.001	0.021	-10000	0	-0.28	1	1
S1P1/S1P	-0.017	0.089	0.24	3	-0.44	3	6
negative regulation of cAMP metabolic process	-0.18	0.25	-10000	0	-0.43	170	170
MAPK3	-0.22	0.3	0.3	3	-0.58	145	148
calcium-dependent phospholipase C activity	-0.003	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.02	0.005	-10000	0	-10000	0	0
RhoA/GDP	0.02	0.005	-10000	0	-10000	0	0
KDR	0.023	0.036	-10000	0	-0.47	2	2
PLCB2	-0.007	0.092	0.24	6	-0.34	5	11
RAC1	0.026	0.006	-10000	0	-10000	0	0
RhoA/GTP	-0.023	0.067	-10000	0	-0.37	3	3
receptor internalization	-0.019	0.08	-10000	0	-0.41	3	3
PTGS2	-0.3	0.44	-10000	0	-0.86	136	136
Rac1/GTP	-0.023	0.067	-10000	0	-0.37	3	3
RHOA	0.026	0.006	-10000	0	-10000	0	0
VEGFA	0.025	0.009	-10000	0	-10000	0	0
negative regulation of T cell proliferation	-0.18	0.25	-10000	0	-0.43	170	170
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	-0.088	0.2	-10000	0	-0.47	87	87
MAPK1	-0.22	0.31	-10000	0	-0.58	146	146
S1P1/S1P/PDGFB-D/PDGFRB	-0.02	0.12	0.25	5	-0.35	13	18
ABCC1	0.026	0.019	0.27	2	-10000	0	2

×

Rapid glucocorticoid 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
Gs family/GDP/Gbeta gamma	-0.074	0.14	-10000	0	-0.24	162	162
MAPK9	0.008	0.002	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.018	0.073	0.29	17	-0.33	6	23
GNB1/GNG2	0.031	0.039	-10000	0	-0.28	6	6
GNB1	0.027	0.003	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.008	0.001	-10000	0	-10000	0	0
Gs family/GTP	-0.094	0.13	-10000	0	-0.25	163	163
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.028	0.034	0.069	163	-10000	0	163
GNAL	-0.17	0.24	-10000	0	-0.47	163	163
GNG2	0.02	0.06	-10000	0	-0.47	6	6
CRH	0.059	0.12	0.23	106	-0.47	6	112
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.005	0.027	-10000	0	-0.31	3	3
MAPK11	0.008	0.002	-10000	0	-10000	0	0

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.056	0.17	0.28	1	-0.26	155	156
SMAD6-7/SMURF1	0.051	0.027	-10000	0	-0.28	1	1
NOG	0.035	0.056	0.22	31	-10000	0	31
SMAD9	-0.15	0.26	-10000	0	-0.52	124	124
SMAD4	0.026	0.007	-10000	0	-10000	0	0
SMAD5	-0.03	0.12	-10000	0	-0.43	18	18
BMP7/USAG1	-0.19	0.23	-10000	0	-0.39	207	207
SMAD5/SKI	-0.025	0.13	-10000	0	-0.41	20	20
SMAD1	0.028	0.034	-10000	0	-10000	0	0
BMP2	-0.023	0.15	-10000	0	-0.47	40	40
SMAD1/SMAD1/SMAD4	0.028	0.056	-10000	0	-0.4	1	1
BMPR1A	0.027	0.006	-10000	0	-10000	0	0
BMPR1B	0.041	0.09	0.21	54	-0.47	6	60
BMPR1A-1B/BAMBI	0.032	0.11	-10000	0	-0.29	35	35
AHSG	0.023	0.075	0.22	46	-10000	0	46
CER1	-0.006	0.017	-10000	0	-10000	0	0
BMP2-4/CER1	-0.003	0.12	-10000	0	-0.29	53	53
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.056	0.14	-10000	0	-0.37	36	36
BMP2-4 (homodimer)	-0.012	0.13	-10000	0	-0.34	54	54
RGMB	0.026	0.006	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.071	0.062	-10000	0	-0.26	6	6
RGMA	-0.11	0.22	-10000	0	-0.47	114	114
SMURF1	0.027	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.054	0.13	-10000	0	-0.36	37	37
BMP2-4/USAG1	-0.09	0.18	-10000	0	-0.31	151	151
SMAD6/SMURF1/SMAD5	-0.025	0.13	-10000	0	-0.4	20	20
SOSTDC1	-0.14	0.22	0.21	6	-0.47	125	131
BMP7/BMPR2/BMPR1A-1B	-0.05	0.16	-10000	0	-0.26	143	143
SKI	0.027	0.003	-10000	0	-10000	0	0
BMP6 (homodimer)	0.026	0.028	0.21	2	-0.47	1	3
HFE2	0.004	0.029	0.21	4	-10000	0	4
ZFYVE16	0.027	0.006	-10000	0	-10000	0	0
MAP3K7	0.026	0.006	-10000	0	-10000	0	0
BMP2-4/CHRD	-0.019	0.15	-10000	0	-0.32	74	74
SMAD5/SMAD5/SMAD4	-0.023	0.13	-10000	0	-0.41	19	19
MAPK1	0.027	0.005	-10000	0	-10000	0	0
TAK1/TAB family	-0.034	0.12	-10000	0	-0.34	29	29
BMP7 (homodimer)	-0.15	0.23	-10000	0	-0.47	141	141
NUP214	0.025	0.008	-10000	0	-10000	0	0
BMP6/FETUA	0.048	0.047	0.24	4	-10000	0	4
SMAD1/SKI	0.036	0.068	-10000	0	-0.38	2	2
SMAD6	0.027	0.03	0.21	3	-0.47	1	4
CTDSP2	0.027	0.005	-10000	0	-10000	0	0
BMP2-4/FETUA	0.012	0.13	0.24	3	-0.3	51	54
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	-0.013	0.19	0.21	61	-0.47	55	116
BMPR2 (homodimer)	0.027	0.005	-10000	0	-10000	0	0
GADD34/PP1CA	0.051	0.016	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	0.049	0.065	-10000	0	-0.34	6	6
CHRDL1	-0.26	0.24	-10000	0	-0.47	229	229
ENDOFIN/SMAD1	0.036	0.066	-10000	0	-0.48	1	1
SMAD6-7/SMURF1/SMAD1	0.056	0.072	-10000	0	-0.46	1	1
SMAD6/SMURF1	0.027	0.004	-10000	0	-10000	0	0
BAMBI	-0.006	0.13	0.21	7	-0.47	29	36
SMURF2	0.027	0.006	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.17	0.19	-10000	0	-0.32	241	241
BMP2-4/GREM1	-0.024	0.17	-10000	0	-0.29	104	104
SMAD7	0.026	0.007	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.14	0.26	-10000	0	-0.49	124	124
SMAD1/SMAD6	0.036	0.068	-10000	0	-0.49	1	1
TAK1/SMAD6	0.038	0.011	-10000	0	-10000	0	0
BMP7	-0.15	0.23	-10000	0	-0.47	141	141
BMP6	0.026	0.028	0.21	2	-0.47	1	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.049	0.14	-10000	0	-0.36	41	41
PPM1A	0.027	0.004	-10000	0	-10000	0	0
SMAD1/SMURF2	0.036	0.067	-10000	0	-0.49	1	1
SMAD7/SMURF1	0.038	0.011	-10000	0	-10000	0	0
CTDSPL	0.026	0.006	-10000	0	-10000	0	0
PPP1CA	0.027	0.005	-10000	0	-10000	0	0
XIAP	0.028	0.015	0.33	1	-10000	0	1
CTDSP1	0.026	0.007	-10000	0	-10000	0	0
PPP1R15A	0.027	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.072	0.16	0.2	1	-0.42	46	47
CHRD	-0.016	0.14	0.21	1	-0.47	35	36
BMPR2	0.027	0.005	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.066	0.14	-10000	0	-0.39	37	37
BMP4	0.008	0.1	0.21	5	-0.47	17	22
FST	0.005	0.11	0.21	10	-0.47	21	31
BMP2-4/NOG	0.009	0.13	0.29	3	-0.29	54	57
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.039	0.16	-10000	0	-0.25	140	140

×

IL6-mediated signaling events

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
BCL2L1	-0.013	0.21	-10000	0	-0.71	10	10
CRP	-0.015	0.21	0.55	3	-0.67	11	14
cell cycle arrest	-0.04	0.23	-10000	0	-0.61	32	32
TIMP1	-0.014	0.19	-10000	0	-0.61	12	12
IL6ST	-0.039	0.17	-10000	0	-0.47	55	55
Rac1/GDP	-0.1	0.23	-10000	0	-0.46	85	85
AP1	-0.012	0.16	-10000	0	-0.47	14	14
GAB2	0.028	0.026	-10000	0	-0.46	1	1
TNFSF11	-0.034	0.22	-10000	0	-0.76	15	15
HSP90B1	0.032	0.07	-10000	0	-0.54	2	2
GAB1	0.028	0.007	-10000	0	-10000	0	0
MAPK14	-0.15	0.27	-10000	0	-0.62	79	79
AKT1	0.04	0.045	-10000	0	-0.32	2	2
FOXO1	0.041	0.049	-10000	0	-0.3	1	1
MAP2K6	-0.14	0.24	-10000	0	-0.51	89	89
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
MAP2K4	-0.077	0.22	0.43	1	-0.46	73	74
MITF	-0.13	0.23	-10000	0	-0.48	92	92
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.027	0.005	-10000	0	-10000	0	0
A2M	-0.11	0.41	-10000	0	-1.3	41	41
CEBPB	0.03	0.026	-10000	0	-0.47	1	1
GRB2/SOS1/GAB family/SHP2	0.002	0.11	0.3	3	-0.52	5	8
STAT3	-0.047	0.24	-10000	0	-0.66	30	30
STAT1	-0.005	0.14	-10000	0	-0.83	10	10
CEBPD	-0.02	0.22	0.49	2	-0.61	21	23
PIK3CA	0.027	0.007	-10000	0	-10000	0	0
PI3K	0.037	0.023	-10000	0	-0.34	1	1
JUN	0.01	0.09	-10000	0	-0.47	14	14
PIAS3/MITF	-0.11	0.22	-10000	0	-0.46	83	83
MAPK11	-0.15	0.27	-10000	0	-0.61	81	81
STAT3 (dimer)/FOXO1	-0.029	0.22	0.4	1	-0.56	30	31
GRB2/SOS1/GAB family	-0.072	0.21	0.29	2	-0.46	58	60
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.12	0.22	-10000	0	-0.34	161	161
GRB2	0.029	0.007	-10000	0	-10000	0	0
JAK2	0.024	0.01	-10000	0	-10000	0	0
LBP	0.007	0.18	-10000	0	-0.61	6	6
PIK3R1	0.026	0.026	-10000	0	-0.47	1	1
JAK1	0.026	0.016	-10000	0	-10000	0	0
MYC	-0.034	0.29	0.51	1	-0.97	23	24
FGG	-0.031	0.2	-10000	0	-0.63	15	15
macrophage differentiation	-0.04	0.23	-10000	0	-0.61	32	32
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.1	0.21	-10000	0	-0.3	183	183
JUNB	-0.037	0.22	-10000	0	-0.69	19	19
FOS	-0.12	0.23	-10000	0	-0.47	124	124
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.12	0.23	-10000	0	-0.49	85	85
STAT1/PIAS1	-0.081	0.21	-10000	0	-0.43	73	73
GRB2/SOS1/GAB family/SHP2/PI3K	0.042	0.04	-10000	0	-0.34	1	1
STAT3 (dimer)	-0.041	0.23	-10000	0	-0.64	30	30
PRKCD	-0.054	0.22	0.4	3	-0.52	47	50
IL6R	-0.012	0.13	-10000	0	-0.47	30	30
SOCS3	-0.2	0.38	0.39	1	-1	62	63
gp130 (dimer)/JAK1/JAK1/LMO4	0.009	0.13	-10000	0	-0.28	56	56
Rac1/GTP	-0.094	0.23	0.27	1	-0.47	81	82
HCK	0.015	0.08	0.21	5	-0.47	10	15
MAPKKK cascade	0.031	0.1	-10000	0	-0.56	5	5
bone resorption	-0.03	0.21	-10000	0	-0.67	18	18
IRF1	-0.032	0.2	-10000	0	-0.59	20	20
mol:GDP	-0.12	0.23	-10000	0	-0.48	87	87
SOS1	0.029	0.008	-10000	0	-10000	0	0
VAV1	-0.12	0.23	-10000	0	-0.49	87	87
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.17	0.31	0.46	1	-0.68	81	82
PTPN11	0.014	0.044	-10000	0	-0.72	1	1
IL6/IL6RA	-0.12	0.21	-10000	0	-0.36	162	162
gp130 (dimer)/TYK2/TYK2/LMO4	0.008	0.12	-10000	0	-0.28	55	55
gp130 (dimer)/JAK2/JAK2/LMO4	0.001	0.12	-10000	0	-0.28	55	55
IL6	-0.18	0.24	-10000	0	-0.47	170	170
PIAS3	0.024	0.009	-10000	0	-10000	0	0
PTPRE	0.015	0.034	0.23	2	-0.46	1	3
PIAS1	0.027	0.004	-10000	0	-10000	0	0
RAC1	0.027	0.006	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.13	0.21	-10000	0	-0.32	184	184
LMO4	0.027	0.032	-10000	0	-0.48	1	1
STAT3 (dimer)/PIAS3	-0.045	0.22	-10000	0	-0.61	34	34
MCL1	0.062	0.078	0.41	2	-10000	0	2

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.025	0.076	0.79	1	-10000	0	1
VDR	0.026	0.038	0.33	1	-0.47	2	3
FAM120B	0.027	0.006	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.022	0.12	-10000	0	-0.37	17	17
RXRs/LXRs/DNA/Oxysterols	-0.003	0.11	-10000	0	-0.34	16	16
MED1	0.026	0.006	-10000	0	-10000	0	0
mol:9cRA	0.005	0.002	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.003	0.095	-10000	0	-0.26	46	46
RXRs/NUR77	-0.16	0.19	-10000	0	-0.31	226	226
RXRs/PPAR	-0.048	0.12	0.18	1	-0.24	105	106
NCOR2	0.027	0.004	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.018	0.025	-10000	0	-0.33	2	2
RARs/VDR/DNA/Vit D3	0.033	0.089	0.22	1	-0.25	34	35
RARA	0.027	0.005	-10000	0	-10000	0	0
NCOA1	0.027	0.006	-10000	0	-10000	0	0
VDR/VDR/DNA	0.026	0.038	0.33	1	-0.47	2	3
RARs/RARs/DNA/9cRA	0.023	0.08	-10000	0	-0.24	33	33
RARG	0.027	0.004	-10000	0	-10000	0	0
RPS6KB1	0.035	0.1	0.62	11	-10000	0	11
RARs/THRs/DNA/SMRT	-0.003	0.096	-10000	0	-0.25	48	48
THRA	0.027	0.005	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.018	0.025	-10000	0	-0.33	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	-0.017	0.13	-10000	0	-0.24	93	93
NR1H4	-0.068	0.19	0.21	16	-0.47	72	88
RXRs/LXRs/DNA	0.006	0.13	-10000	0	-0.23	73	73
NR1H2	0.032	0.006	-10000	0	-10000	0	0
NR1H3	0.031	0.009	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.011	0.13	0.24	2	-0.24	90	92
NR4A1	-0.25	0.24	-10000	0	-0.47	224	224
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.063	0.15	-10000	0	-0.25	131	131
RXRG	-0.092	0.21	0.33	1	-0.46	95	96
RXR alpha/CCPG	0.038	0.016	-10000	0	-10000	0	0
RXRA	0.029	0.01	-10000	0	-10000	0	0
RXRB	0.033	0.004	-10000	0	-10000	0	0
THRB	-0.003	0.12	-10000	0	-0.47	24	24
PPARG	-0.005	0.12	0.33	2	-0.47	25	27
PPARD	0.027	0.003	-10000	0	-10000	0	0
TNF	0	0.11	-10000	0	-10000	0	0
mol:Oxysterols	0.005	0.002	-10000	0	-10000	0	0
cholesterol transport	-0.003	0.11	-10000	0	-0.33	16	16
PPARA	0.024	0.035	-10000	0	-0.47	2	2
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	-0.015	0.14	-10000	0	-0.47	34	34
RXRs/NUR77/BCL2	-0.17	0.18	0.17	1	-0.3	236	237
SREBF1	-0.003	0.1	-10000	0	-10000	0	0
RXRs/RXRs/DNA/9cRA	-0.017	0.13	-10000	0	-0.24	93	93
ABCA1	-0.001	0.1	-10000	0	-10000	0	0
RARs/THRs	0.032	0.12	-10000	0	-0.28	48	48
RXRs/FXR	-0.059	0.17	-10000	0	-0.29	135	135
BCL2	0.008	0.093	-10000	0	-0.47	15	15

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.028	0.014	0.21	2	-10000	0	2
RAS family/GTP/Tiam1	-0.081	0.11	-10000	0	-0.24	70	70
NT3 (dimer)/TRKC	-0.19	0.23	-10000	0	-0.39	215	215
NT3 (dimer)/TRKB	-0.17	0.25	0.26	1	-0.4	193	194
SHC/Grb2/SOS1/GAB1/PI3K	0.026	0.015	-10000	0	-10000	0	0
RAPGEF1	0.025	0.009	-10000	0	-10000	0	0
BDNF	-0.056	0.18	-10000	0	-0.47	67	67
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
DYNLT1	0.027	0.005	-10000	0	-10000	0	0
NTRK1	0.025	0.031	0.23	7	-10000	0	7
NTRK2	-0.13	0.23	0.21	7	-0.47	131	138
NTRK3	-0.21	0.24	-10000	0	-0.47	189	189
NT-4/5 (dimer)/TRKB	-0.14	0.22	0.29	1	-0.37	179	180
neuron apoptosis	0.17	0.23	0.48	117	-10000	0	117
SHC 2-3/Grb2	-0.18	0.26	-10000	0	-0.53	117	117
SHC1	0.026	0.017	0.33	1	-10000	0	1
SHC2	-0.18	0.27	-10000	0	-0.56	106	106
SHC3	-0.19	0.26	-10000	0	-0.52	124	124
STAT3 (dimer)	0.032	0.054	-10000	0	-0.33	7	7
NT3 (dimer)/TRKA	-0.066	0.18	0.25	3	-0.32	124	127
RIN/GDP	-0.05	0.11	0.24	3	-0.23	34	37
GIPC1	0.027	0.004	-10000	0	-10000	0	0
KRAS	0.027	0.016	0.33	1	-10000	0	1
DNAJA3	-0.073	0.15	-10000	0	-0.32	96	96
RIN/GTP	0.012	0.008	0.15	1	-10000	0	1
CCND1	0.017	0.12	0.36	13	-0.73	7	20
MAGED1	0.027	0.003	-10000	0	-10000	0	0
PTPN11	0.027	0.005	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.007	0.12	-10000	0	-0.47	27	27
SHC/GRB2/SOS1	0.05	0.021	0.24	1	-10000	0	1
GRB2	0.027	0.005	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.001	0.14	0.24	1	-0.32	57	58
TRKA/NEDD4-2	0.037	0.022	0.24	1	-10000	0	1
ELMO1	0.023	0.043	-10000	0	-0.47	3	3
RhoG/GTP/ELMO1/DOCK1	0.031	0.04	-10000	0	-0.34	4	4
NGF	-0.039	0.17	-10000	0	-0.47	53	53
HRAS	0.025	0.008	-10000	0	-10000	0	0
DOCK1	0.024	0.035	-10000	0	-0.47	2	2
GAB2	0.025	0.025	-10000	0	-0.47	1	1
RIT2	-0.012	0.016	0.21	1	-10000	0	1
RIT1	0.026	0.007	-10000	0	-10000	0	0
FRS2	0.031	0.04	0.33	7	-10000	0	7
DNM1	0.017	0.06	-10000	0	-0.47	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.008	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.055	0.16	-10000	0	-0.3	100	100
mol:GDP	-0.077	0.15	0.33	2	-0.33	45	47
NGF (dimer)	-0.039	0.17	-10000	0	-0.47	53	53
RhoG/GDP	0.017	0.031	-10000	0	-0.33	3	3
RIT1/GDP	-0.048	0.11	0.28	2	-0.24	29	31
TIAM1	0.023	0.043	-10000	0	-0.47	3	3
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
BDNF (dimer)/TRKB	-0.11	0.2	-10000	0	-0.33	167	167
KIDINS220/CRKL/C3G	0.036	0.017	-10000	0	-10000	0	0
SHC/RasGAP	0.037	0.017	0.24	1	-10000	0	1
FRS2 family/SHP2	0.053	0.029	0.24	6	-10000	0	6
SHC/GRB2/SOS1/GAB1	0.06	0.028	0.24	1	-10000	0	1
RIT1/GTP	0.019	0.005	-10000	0	-10000	0	0
NT3 (dimer)	-0.063	0.19	0.21	1	-0.47	72	73
RAP1/GDP	-0.048	0.086	-10000	0	-0.2	27	27
KIDINS220/CRKL	0.027	0.014	0.21	2	-10000	0	2
BDNF (dimer)	-0.056	0.18	-10000	0	-0.47	67	67
ubiquitin-dependent protein catabolic process	0.012	0.11	0.23	1	-0.28	43	44
Schwann cell development	-0.046	0.035	-10000	0	-10000	0	0
EHD4	0.027	0.005	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.064	0.035	0.24	7	-10000	0	7
FRS2 family/SHP2/CRK family/C3G/GAB2	0.021	0.057	-10000	0	-0.26	3	3
RAP1B	0.026	0.008	-10000	0	-10000	0	0
RAP1A	0.028	0.003	-10000	0	-10000	0	0
CDC42/GTP	-0.24	0.24	0.34	1	-0.38	261	262
ABL1	0.025	0.009	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.039	0.01	-10000	0	-10000	0	0
Rap1/GTP	-0.044	0.11	-10000	0	-0.37	14	14
STAT3	0.032	0.054	-10000	0	-0.33	7	7
axon guidance	-0.23	0.22	-10000	0	-0.36	261	261
MAPK3	-0.021	0.11	0.19	15	-0.28	55	70
MAPK1	-0.022	0.12	0.19	16	-0.29	55	71
CDC42/GDP	-0.048	0.11	0.25	3	-0.24	28	31
NTF3	-0.063	0.19	0.21	1	-0.47	72	73
NTF4	-0.007	0.12	-10000	0	-0.47	27	27
NGF (dimer)/TRKA/FAIM	0.012	0.11	0.24	1	-0.29	45	46
PI3K	0.035	0.023	-10000	0	-0.34	1	1
FRS3	0.027	0.004	-10000	0	-10000	0	0
FAIM	0.026	0.006	-10000	0	-10000	0	0
GAB1	0.026	0.006	-10000	0	-10000	0	0
RASGRF1	-0.078	0.15	0.17	1	-0.31	104	105
SOS1	0.027	0.005	-10000	0	-10000	0	0
MCF2L	-0.18	0.2	-10000	0	-0.35	213	213
RGS19	0.026	0.012	0.21	1	-10000	0	1
CDC42	0.028	0.003	-10000	0	-10000	0	0
RAS family/GTP	0.029	0.089	0.3	2	-0.41	4	6
Rac1/GDP	-0.045	0.11	0.25	3	-0.24	27	30
NGF (dimer)/TRKA/GRIT	-0.002	0.1	-10000	0	-0.28	45	45
neuron projection morphogenesis	-0.058	0.16	-10000	0	-0.5	21	21
NGF (dimer)/TRKA/NEDD4-2	0.012	0.11	0.24	1	-0.28	43	44
MAP2K1	0.04	0.069	0.4	5	-10000	0	5
NGFR	-0.076	0.2	0.24	5	-0.47	86	91
NGF (dimer)/TRKA/GIPC/GAIP	-0.009	0.1	-10000	0	-0.28	42	42
RAS family/GTP/PI3K	0.022	0.022	0.17	1	-0.3	1	2
FRS2 family/SHP2/GRB2/SOS1	0.072	0.037	-10000	0	-10000	0	0
NRAS	0.028	0.002	-10000	0	-10000	0	0
GRB2/SOS1	0.039	0.01	-10000	0	-10000	0	0
PRKCI	0.026	0.007	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
PRKCZ	0.024	0.043	-10000	0	-0.47	3	3
MAPKKK cascade	-0.092	0.24	-10000	0	-0.67	55	55
RASA1	0.027	0.006	-10000	0	-10000	0	0
TRKA/c-Abl	0.036	0.024	0.24	1	-10000	0	1
SQSTM1	0.026	0.007	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.092	0.19	-10000	0	-0.3	165	165
NGF (dimer)/TRKA/p62/Atypical PKCs	0.032	0.11	-10000	0	-0.25	44	44
MATK	0.001	0.12	0.21	5	-0.47	23	28
NEDD4L	0.026	0.007	-10000	0	-10000	0	0
RAS family/GDP	-0.061	0.064	-10000	0	-0.18	35	35
NGF (dimer)/TRKA	-0.074	0.16	0.18	1	-0.32	104	105
Rac1/GTP	-0.086	0.11	-10000	0	-0.25	97	97
FRS2 family/SHP2/CRK family	0.066	0.042	-10000	0	-10000	0	0

×

PDGFR-alpha signaling 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
PDGFRA	-0.061	0.17	-10000	0	-0.49	55	55
PDGF/PDGFRA/CRKL	-0.028	0.12	-10000	0	-0.34	53	53
positive regulation of JUN kinase activity	0.019	0.1	0.24	1	-0.26	44	45
CRKL	0.028	0.014	0.21	2	-10000	0	2
PDGF/PDGFRA/Caveolin-3	-0.033	0.12	-10000	0	-0.35	51	51
AP1	-0.29	0.43	-10000	0	-0.9	128	128
mol:IP3	-0.052	0.12	-10000	0	-0.36	51	51
PLCG1	-0.052	0.12	-10000	0	-0.36	51	51
PDGF/PDGFRA/alphaV Integrin	-0.029	0.13	-10000	0	-0.34	55	55
RAPGEF1	0.025	0.009	-10000	0	-10000	0	0
CRK	0.025	0.008	-10000	0	-10000	0	0
mol:Ca2+	-0.052	0.12	-10000	0	-0.36	51	51
CAV3	-0.003	0.029	0.25	3	-10000	0	3
CAV1	0.005	0.1	-10000	0	-0.47	18	18
SHC/Grb2/SOS1	0.021	0.1	0.24	1	-0.26	44	45
PDGF/PDGFRA/Shf	-0.034	0.14	-10000	0	-0.36	58	58
FOS	-0.3	0.41	-10000	0	-0.89	128	128
JUN	-0.048	0.075	-10000	0	-0.4	14	14
oligodendrocyte development	-0.029	0.13	-10000	0	-0.34	55	55
GRB2	0.027	0.005	-10000	0	-10000	0	0
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
mol:DAG	-0.052	0.12	-10000	0	-0.36	51	51
PDGF/PDGFRA	-0.061	0.17	-10000	0	-0.49	55	55
actin cytoskeleton reorganization	-0.028	0.12	-10000	0	-0.34	52	52
SRF	0.021	0.014	-10000	0	-10000	0	0
SHC1	0.026	0.017	0.33	1	-10000	0	1
PI3K	0.004	0.11	-10000	0	-0.28	49	49
PDGF/PDGFRA/Crk/C3G	0	0.11	-10000	0	-0.28	53	53
JAK1	-0.044	0.12	-10000	0	-0.34	55	55
ELK1/SRF	-0.032	0.11	0.17	5	-0.29	51	56
SHB	0.024	0.009	-10000	0	-10000	0	0
SHF	0.02	0.06	-10000	0	-0.47	6	6
CSNK2A1	0.039	0.024	-10000	0	-10000	0	0
GO:0007205	-0.059	0.13	-10000	0	-0.39	51	51
SOS1	0.027	0.005	-10000	0	-10000	0	0
Ras protein signal transduction	0.019	0.1	0.24	1	-0.26	44	45
PDGF/PDGFRA/SHB	-0.028	0.12	-10000	0	-0.34	52	52
PDGF/PDGFRA/Caveolin-1	-0.042	0.15	-10000	0	-0.39	60	60
ITGAV	0.027	0.006	-10000	0	-10000	0	0
ELK1	-0.064	0.12	0.23	2	-0.35	52	54
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk	-0.028	0.12	-10000	0	-0.34	53	53
JAK-STAT cascade	-0.044	0.12	-10000	0	-0.34	55	55
cell proliferation	-0.034	0.14	-10000	0	-0.35	58	58

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.035	0.14	0.29	1	-0.38	45	46
alphaM/beta2 Integrin/GPIbA	-0.011	0.11	0.29	2	-0.36	21	23
alphaM/beta2 Integrin/proMMP-9	0.019	0.14	0.28	11	-0.42	20	31
PLAUR	0.027	0.005	-10000	0	-10000	0	0
HMGB1	-0.006	0.04	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.012	0.1	0.29	1	-0.37	19	20
AGER	-0.004	0.047	0.22	2	-10000	0	2
RAP1A	0.028	0.003	-10000	0	-10000	0	0
SELPLG	0.02	0.066	0.21	2	-0.47	7	9
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.054	0.16	0.3	1	-0.34	36	37
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.068	0.1	0.22	102	-0.47	5	107
CYR61	-0.11	0.22	-10000	0	-0.47	114	114
TLN1	0.025	0.009	-10000	0	-10000	0	0
Rap1/GTP	-0.004	0.14	-10000	0	-0.45	22	22
RHOA	0.026	0.006	-10000	0	-10000	0	0
P-selectin oligomer	-0.065	0.19	-10000	0	-0.47	73	73
MYH2	-0.024	0.13	-10000	0	-0.4	25	25
MST1R	0.013	0.095	0.23	8	-0.47	14	22
leukocyte activation during inflammatory response	-0.061	0.14	0.25	1	-0.29	97	98
APOB	-0.049	0.17	0.23	7	-0.47	57	64
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	-0.011	0.13	-10000	0	-0.47	31	31
JAM3	-0.004	0.12	-10000	0	-0.47	25	25
GP1BA	0.024	0.039	0.21	8	-0.47	1	9
alphaM/beta2 Integrin/CTGF	-0.064	0.18	0.29	1	-0.38	81	82
alphaM/beta2 Integrin	-0.027	0.15	-10000	0	-0.49	25	25
JAM3 homodimer	-0.004	0.12	-10000	0	-0.47	25	25
ICAM2	0.025	0.025	-10000	0	-0.47	1	1
ICAM1	0.03	0.037	0.21	9	-0.47	1	10
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.026	0.15	-10000	0	-0.46	27	27
cell adhesion	-0.011	0.11	0.29	2	-0.36	21	23
NFKB1	-0.13	0.21	0.34	5	-0.36	166	171
THY1	0.028	0.017	0.21	3	-10000	0	3
RhoA/GDP	0.02	0.005	-10000	0	-10000	0	0
Lipoprotein(a)	-0.034	0.14	-10000	0	-0.3	81	81
alphaM/beta2 Integrin/LRP/tPA	-0.015	0.13	0.33	2	-0.36	34	36
IL6	-0.29	0.37	0.37	3	-0.69	180	183
ITGB2	-0.012	0.081	0.21	8	-0.49	7	15
elevation of cytosolic calcium ion concentration	0.013	0.12	0.29	2	-0.34	19	21
alphaM/beta2 Integrin/JAM2/JAM3	-0.083	0.2	0.3	1	-0.36	113	114
JAM2	-0.099	0.22	-10000	0	-0.47	103	103
alphaM/beta2 Integrin/ICAM1	0.007	0.12	0.33	2	-0.3	32	34
alphaM/beta2 Integrin/uPA/Plg	0.012	0.12	0.29	2	-0.34	21	23
RhoA/GTP	-0.024	0.13	-10000	0	-0.4	27	27
positive regulation of phagocytosis	-0.022	0.15	0.21	2	-0.47	27	29
Ron/MSP	0.034	0.081	0.3	1	-0.34	15	16
alphaM/beta2 Integrin/uPAR/uPA	0.015	0.12	0.3	2	-0.34	19	21
alphaM/beta2 Integrin/uPAR	-0.013	0.11	0.29	1	-0.36	20	21
PLAU	0.052	0.065	0.22	53	-10000	0	53
PLAT	0.005	0.1	0.33	2	-0.47	17	19
actin filament polymerization	-0.022	0.12	0.23	1	-0.38	25	26
MST1	0.036	0.052	0.22	22	-0.47	1	23
alphaM/beta2 Integrin/lipoprotein(a)	-0.058	0.15	0.27	1	-0.29	97	98
TNF	-0.12	0.19	0.4	2	-0.34	160	162
RAP1B	0.026	0.008	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.005	0.12	0.27	4	-0.36	21	25
fibrinolysis	0.01	0.12	0.28	2	-0.34	21	23
HCK	0.014	0.08	0.21	5	-0.47	10	15
dendritic cell antigen processing and presentation	-0.026	0.15	-10000	0	-0.46	27	27
VTN	-0.045	0.18	0.21	7	-0.47	60	67
alphaM/beta2 Integrin/CYR61	-0.09	0.2	0.29	1	-0.38	112	113
LPA	-0.022	0.13	0.21	6	-0.47	31	37
LRP1	0.022	0.049	-10000	0	-0.47	4	4
cell migration	-0.028	0.15	0.24	5	-0.39	41	46
FN1	0.025	0.094	0.21	26	-0.47	11	37
alphaM/beta2 Integrin/Thy1	-0.011	0.11	0.29	1	-0.36	21	22
MPO	0.021	0.021	0.21	2	-10000	0	2
KNG1	-0.016	0.004	-10000	0	-10000	0	0
RAP1/GDP	0.034	0.011	-10000	0	-10000	0	0
ROCK1	-0.014	0.13	-10000	0	-0.4	24	24
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.005	0.03	0.21	5	-10000	0	5
CTGF	-0.067	0.19	-10000	0	-0.47	76	76
alphaM/beta2 Integrin/Hck	-0.014	0.13	0.29	4	-0.43	22	26
ITGAM	-0.027	0.11	0.22	2	-0.49	18	20
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.052	0.16	0.3	2	-0.33	80	82
HP	0.037	0.073	0.22	44	-0.47	2	46
leukocyte adhesion	-0.12	0.21	0.29	1	-0.44	89	90
SELP	-0.065	0.19	-10000	0	-0.47	73	73

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.021	0.12	-10000	0	-0.29	45	45
MAP4K1	0.015	0.079	0.21	3	-0.47	10	13
MAP3K8	0.024	0.035	-10000	0	-0.47	2	2
PRKCB	-0.11	0.22	-10000	0	-0.47	112	112
DBNL	0.027	0.005	-10000	0	-10000	0	0
CRKL	0.028	0.014	0.21	2	-10000	0	2
MAP3K1	-0.005	0.11	-10000	0	-0.4	16	16
JUN	-0.17	0.3	-10000	0	-0.6	125	125
MAP3K7	-0.006	0.11	-10000	0	-0.38	18	18
GRAP2	-0.026	0.15	-10000	0	-0.47	43	43
CRK	0.025	0.008	-10000	0	-10000	0	0
MAP2K4	-0.008	0.12	-10000	0	-0.4	22	22
LAT	0.027	0.011	0.21	1	-10000	0	1
LCP2	0.022	0.043	-10000	0	-0.47	3	3
MAPK8	-0.17	0.31	-10000	0	-0.61	127	127
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.002	0.12	-10000	0	-0.3	40	40
LAT/GRAP2/SLP76/HPK1/HIP-55	0.03	0.11	-10000	0	-0.27	43	43

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.099	0.21	-10000	0	-0.38	133	133
fibroblast growth factor receptor signaling pathway	-0.099	0.21	-10000	0	-0.38	133	133
LAMA1	0.04	0.12	0.22	66	-0.47	14	80
PRNP	0.015	0.073	-10000	0	-0.47	9	9
GPC1/SLIT2	-0.12	0.18	-10000	0	-0.33	168	168
SMAD2	0.017	0.033	-10000	0	-0.26	2	2
GPC1/PrPc/Cu2+	0.025	0.048	-10000	0	-0.28	9	9
GPC1/Laminin alpha1	0.044	0.089	0.25	5	-0.33	14	19
TDGF1	0.009	0.028	0.21	3	-10000	0	3
CRIPTO/GPC1	0.034	0.017	-10000	0	-10000	0	0
APP/GPC1	0.036	0.023	-10000	0	-0.32	1	1
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.013	0.008	-10000	0	-10000	0	0
FLT1	0.027	0.005	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.043	0.033	-10000	0	-0.28	2	2
SERPINC1	0.033	0.056	0.22	30	-10000	0	30
FYN	0.011	0.027	-10000	0	-0.28	3	3
FGR	0.012	0.022	-10000	0	-0.29	2	2
positive regulation of MAPKKK cascade	0.004	0.1	0.26	12	-0.31	14	26
SLIT2	-0.18	0.24	-10000	0	-0.47	168	168
GPC1/NRG	-0.013	0.13	0.24	2	-0.33	56	58
NRG1	-0.038	0.18	0.22	18	-0.47	56	74
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.048	0.021	-10000	0	-10000	0	0
LYN	0.013	0.008	-10000	0	-10000	0	0
mol:Spermine	0.007	0.003	-10000	0	-10000	0	0
cell growth	-0.099	0.21	-10000	0	-0.38	133	133
BMP signaling pathway	-0.026	0.012	-10000	0	-0.21	1	1
SRC	0.013	0.008	-10000	0	-10000	0	0
TGFBR1	0.025	0.009	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.19	0.25	0.21	3	-0.47	178	181
GPC1	0.026	0.012	0.21	1	-10000	0	1
TGFBR1 (dimer)	0.025	0.009	-10000	0	-10000	0	0
VEGFA	0.027	0.005	-10000	0	-10000	0	0
BLK	-0.01	0.08	-10000	0	-0.28	30	30
HCK	0.006	0.046	-10000	0	-0.29	9	9
FGF2	-0.13	0.23	-10000	0	-0.47	127	127
FGFR1	-0.066	0.19	-10000	0	-0.47	73	73
VEGFR1 homodimer	0.027	0.005	-10000	0	-10000	0	0
TGFBR2	0.024	0.035	-10000	0	-0.47	2	2
cell death	0.036	0.023	-10000	0	-0.31	1	1
ATIII/GPC1	0.042	0.036	0.24	1	-10000	0	1
PLA2G2A/GPC1	-0.12	0.19	-10000	0	-0.33	178	178
LCK	0.011	0.031	-10000	0	-0.28	4	4
neuron differentiation	-0.013	0.13	0.24	2	-0.33	56	58
PrPc/Cu2+	0.012	0.052	-10000	0	-0.33	9	9
APP	0.026	0.025	-10000	0	-0.47	1	1
TGFBR2 (dimer)	0.024	0.035	-10000	0	-0.47	2	2

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0.073	-10000	0	-0.47	9	9
mol:S1P	0	0.004	-10000	0	-10000	0	0
S1P1/S1P/Gi	-0.1	0.17	-10000	0	-0.29	153	153
GNAO1	-0.12	0.23	-10000	0	-0.47	124	124
S1P/S1P3/G12/G13	0.039	0.041	0.22	1	-0.26	4	5
AKT1	-0.047	0.17	-10000	0	-0.61	27	27
AKT3	-0.065	0.24	-10000	0	-1.1	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.016	0.073	-10000	0	-0.47	9	9
GNAI2	0.025	0.012	-10000	0	-10000	0	0
GNAI3	0.027	0.01	-10000	0	-10000	0	0
GNAI1	0.023	0.043	-10000	0	-0.47	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.02	0.053	0.33	1	-0.47	4	5
S1PR2	0.027	0.005	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.1	0.2	-10000	0	-0.36	121	121
MAPK3	-0.098	0.18	-10000	0	-0.42	80	80
MAPK1	-0.1	0.18	-10000	0	-0.42	80	80
JAK2	-0.1	0.21	0.23	1	-0.45	87	88
CXCR4	-0.1	0.19	-10000	0	-0.43	81	81
FLT1	0.027	0.014	-10000	0	-10000	0	0
RhoA/GDP	0.02	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.02	0.005	-10000	0	-10000	0	0
SRC	-0.095	0.18	-10000	0	-0.36	107	107
S1P/S1P3/Gi	-0.1	0.2	-10000	0	-0.36	121	121
RAC1	0.026	0.006	-10000	0	-10000	0	0
RhoA/GTP	-0.092	0.19	-10000	0	-0.4	83	83
VEGFA	0.026	0.014	-10000	0	-10000	0	0
S1P/S1P2/Gi	-0.092	0.18	-10000	0	-0.3	150	150
VEGFR1 homodimer/VEGFA homodimer	0.041	0.022	-10000	0	-10000	0	0
RHOA	0.026	0.006	-10000	0	-10000	0	0
S1P/S1P3/Gq	-0.009	0.093	-10000	0	-0.25	51	51
GNAQ	0.025	0.009	-10000	0	-10000	0	0
GNAZ	-0.08	0.2	-10000	0	-0.47	87	87
G12/G13	0.037	0.012	-10000	0	-10000	0	0
GNA14	-0.03	0.16	-10000	0	-0.47	45	45
GNA15	0.023	0.043	-10000	0	-0.47	3	3
GNA12	0.026	0.007	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
GNA11	0.026	0.025	-10000	0	-0.47	1	1
Rac1/GTP	-0.09	0.18	-10000	0	-0.4	82	82

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.009	0.11	0.27	1	-0.32	22	23
TBX21	-0.13	0.48	-10000	0	-1.2	56	56
B2M	0.025	0.015	-10000	0	-10000	0	0
TYK2	0.018	0.035	-10000	0	-10000	0	0
IL12RB1	0.016	0.1	0.23	20	-0.5	10	30
GADD45B	-0.083	0.39	-10000	0	-0.99	49	49
IL12RB2	0.039	0.1	0.22	58	-0.48	6	64
GADD45G	-0.09	0.38	-10000	0	-0.95	49	49
natural killer cell activation	-0.002	0.022	0.051	4	-0.044	50	54
RELB	0.027	0.005	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
IL18	0.019	0.062	-10000	0	-0.47	6	6
IL2RA	0.012	0.11	0.21	19	-0.47	17	36
IFNG	0.057	0.085	0.22	81	-10000	0	81
STAT3 (dimer)	-0.079	0.34	-10000	0	-0.81	60	60
HLA-DRB5	-0.006	0.01	-10000	0	-0.023	98	98
FASLG	-0.12	0.47	-10000	0	-1.2	60	60
NF kappa B2 p52/RelB	-0.11	0.44	-10000	0	-1	62	62
CD4	0.01	0.041	-10000	0	-0.47	2	2
SOCS1	0.027	0.011	0.21	1	-10000	0	1
EntrezGene:6955	-0.007	0.015	-10000	0	-0.027	120	120
CD3D	-0.028	0.14	0.2	3	-0.47	32	35
CD3E	-0.036	0.14	-10000	0	-0.47	39	39
CD3G	-0.041	0.15	-10000	0	-0.47	42	42
IL12Rbeta2/JAK2	0.037	0.087	0.24	3	-0.36	6	9
CCL3	-0.13	0.47	-10000	0	-1.2	55	55
CCL4	-0.15	0.52	-10000	0	-1.3	59	59
HLA-A	0	0.008	-10000	0	-0.04	14	14
IL18/IL18R	0.046	0.1	-10000	0	-0.31	26	26
NOS2	-0.093	0.4	-10000	0	-1	50	50
IL12/IL12R/TYK2/JAK2/SPHK2	0.009	0.12	0.27	1	-0.33	20	21
IL1R1	-0.11	0.43	-10000	0	-1.1	53	53
IL4	0.001	0.036	-10000	0	-10000	0	0
JAK2	0.017	0.033	-10000	0	-10000	0	0
EntrezGene:6957	-0.006	0.013	-10000	0	-0.025	110	110
TCR/CD3/MHC I/CD8	-0.12	0.34	-10000	0	-0.77	68	68
RAB7A	-0.049	0.31	-10000	0	-0.8	41	41
lysosomal transport	-0.043	0.3	-10000	0	-0.75	41	41
FOS	-0.4	0.62	-10000	0	-1.2	153	153
STAT4 (dimer)	-0.074	0.39	0.45	1	-0.91	59	60
STAT5A (dimer)	-0.094	0.45	0.49	1	-1	62	63
GZMA	-0.15	0.51	-10000	0	-1.3	58	58
GZMB	-0.14	0.48	-10000	0	-1.3	53	53
HLX	0.028	0.01	0.21	1	-10000	0	1
LCK	-0.14	0.49	-10000	0	-1.2	62	62
TCR/CD3/MHC II/CD4	-0.1	0.2	-10000	0	-0.32	145	145
IL2/IL2R	0.039	0.11	0.29	4	-0.32	24	28
MAPK14	-0.081	0.39	-10000	0	-0.94	54	54
CCR5	-0.089	0.4	-10000	0	-1.1	47	47
IL1B	0.005	0.12	0.23	15	-0.49	18	33
STAT6	-0.008	0.15	-10000	0	-0.71	6	6
STAT4	0.002	0.11	-10000	0	-0.47	20	20
STAT3	0.027	0.004	-10000	0	-10000	0	0
STAT1	0.029	0.019	0.21	4	-10000	0	4
NFKB1	0.027	0.004	-10000	0	-10000	0	0
NFKB2	0.027	0.005	-10000	0	-10000	0	0
IL12B	0.018	0.055	0.23	14	-10000	0	14
CD8A	-0.021	0.15	0.22	1	-0.47	39	40
CD8B	-0.014	0.14	0.22	7	-0.47	35	42
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.009	0.11	0.32	21	-0.27	1	22
IL2RB	0.022	0.058	0.27	2	-0.47	5	7
proteasomal ubiquitin-dependent protein catabolic process	-0.059	0.35	0.45	1	-0.81	59	60
IL2RG	0.021	0.079	0.21	9	-0.47	9	18
IL12	0.029	0.064	0.28	2	-10000	0	2
STAT5A	0.026	0.025	-10000	0	-0.47	1	1
CD247	0.004	0.064	0.21	1	-0.47	6	7
IL2	-0.005	0.02	-10000	0	-10000	0	0
SPHK2	0.028	0.01	0.21	1	-10000	0	1
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.021	0.046	0.24	7	-10000	0	7
IL12/IL12R/TYK2/JAK2	-0.16	0.57	-10000	0	-1.3	63	63
MAP2K3	-0.094	0.41	-10000	0	-0.97	57	57
RIPK2	0.024	0.01	-10000	0	-10000	0	0
MAP2K6	-0.082	0.38	-10000	0	-0.92	56	56
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.007	0.012	-10000	0	-0.026	109	109
IL18RAP	0.002	0.11	-10000	0	-0.47	20	20
IL12Rbeta1/TYK2	0.028	0.085	0.22	4	-0.39	9	13
EOMES	-0.065	0.29	-10000	0	-1.1	25	25
STAT1 (dimer)	-0.05	0.35	0.46	1	-0.8	57	58
T cell proliferation	-0.047	0.28	0.41	1	-0.64	57	58
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.025	0.039	-10000	0	-0.48	2	2
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.069	0.28	-10000	0	-0.68	59	59
ATF2	-0.071	0.35	-10000	0	-0.85	54	54

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.027	0.005	-10000	0	-10000	0	0
VLDLR	0.012	0.077	-10000	0	-0.47	10	10
LRPAP1	0.027	0.016	0.33	1	-10000	0	1
NUDC	0.027	0.003	-10000	0	-10000	0	0
RELN/LRP8	-0.051	0.18	0.27	5	-0.29	135	140
CaM/Ca2+	0.02	0.003	-10000	0	-10000	0	0
KATNA1	0.027	0.006	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.079	0.13	0.19	8	-0.26	134	142
IQGAP1/CaM	0.039	0.009	-10000	0	-10000	0	0
DAB1	-0.016	0.14	0.22	25	-0.47	33	58
IQGAP1	0.027	0.004	-10000	0	-10000	0	0
PLA2G7	0.052	0.064	0.22	52	-10000	0	52
CALM1	0.027	0.005	-10000	0	-10000	0	0
DYNLT1	0.027	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.062	0.052	0.17	69	-10000	0	69
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.027	0.004	-10000	0	-10000	0	0
CDK5R1	0.038	0.05	0.24	22	-10000	0	22
LIS1/Poliovirus Protein 3A	0.01	0.004	-10000	0	-10000	0	0
CDK5R2	0.026	0.051	0.21	25	-10000	0	25
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.09	0.18	0.23	1	-0.31	157	158
YWHAE	0.025	0.008	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.055	0.12	0.28	1	-0.26	22	23
MAP1B	-0.023	0.085	-10000	0	-0.28	41	41
RAC1	0.013	0.007	-10000	0	-10000	0	0
p35/CDK5	-0.058	0.12	0.19	6	-0.24	121	127
RELN	-0.15	0.23	0.21	4	-0.47	139	143
PAFAH/LIS1	0.044	0.047	0.23	2	-10000	0	2
LIS1/CLIP170	0.027	0.012	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.039	0.1	-10000	0	-0.25	1	1
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.091	0.17	0.28	1	-0.39	62	63
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.064	0.12	0.21	1	-0.25	53	54
LIS1/IQGAP1	0.027	0.011	-10000	0	-10000	0	0
RHOA	0.014	0.006	-10000	0	-10000	0	0
PAFAH1B1	0.013	0.005	-10000	0	-10000	0	0
PAFAH1B3	0.038	0.048	0.23	22	-10000	0	22
PAFAH1B2	0.026	0.006	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0	0.065	-10000	0	-0.29	1	1
NDEL1/Katanin 60/Dynein heavy chain	-0.047	0.12	0.28	1	-0.26	20	21
LRP8	0.062	0.073	0.22	74	-10000	0	74
NDEL1/Katanin 60	-0.057	0.12	0.28	1	-0.26	23	24
P39/CDK5	-0.064	0.13	0.22	6	-0.24	133	139
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.027	0.011	-10000	0	-10000	0	0
CDK5	-0.086	0.12	0.18	7	-0.24	133	140
PPP2R5D	0.027	0.004	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.023	0.01	-10000	0	-10000	0	0
CSNK2A1	0.026	0.006	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.069	0.16	0.28	1	-0.27	147	148
RELN/VLDLR	-0.043	0.17	0.28	4	-0.27	136	140
CDC42	0.014	0.006	-10000	0	-10000	0	0

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.028	0.044	0.13	3	-0.18	22	25
BUB1B	0.026	0.042	0.15	8	-0.16	6	14
PLK1	0.02	0.029	0.11	16	-0.098	1	17
PLK1S1	0.017	0.029	0.11	15	-0.16	4	19
KIF2A	0.015	0.026	0.14	1	-10000	0	1
regulation of mitotic centrosome separation	0.02	0.029	0.11	16	-0.097	1	17
GOLGA2	0.025	0.009	-10000	0	-10000	0	0
Hec1/SPC24	0.13	0.11	0.26	153	-10000	0	153
WEE1	0.007	0.093	-10000	0	-0.31	30	30
cytokinesis	0.043	0.07	0.2	6	-0.24	13	19
PP2A-alpha B56	0.07	0.089	-10000	0	-0.51	7	7
AURKA	0.034	0.037	0.15	15	-0.17	1	16
PICH/PLK1	0.041	0.048	0.2	13	-10000	0	13
CENPE	0.011	0.03	0.16	3	-0.19	1	4
RhoA/GTP	0.02	0.005	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.016	0.026	0.14	1	-10000	0	1
PPP2CA	0.027	0.005	-10000	0	-10000	0	0
FZR1	0.027	0.005	-10000	0	-10000	0	0
TPX2	0.053	0.049	0.16	46	-10000	0	46
PAK1	0.025	0.026	-10000	0	-0.47	1	1
SPC24	0.099	0.093	0.22	153	-10000	0	153
FBXW11	0.026	0.007	-10000	0	-10000	0	0
CLSPN	0.04	0.037	0.15	5	-0.2	1	6
GORASP1	0.026	0.006	-10000	0	-10000	0	0
metaphase	0.001	0.003	0.013	9	-0.011	3	12
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.008	0.015	0.053	17	-0.053	1	18
G2 phase of mitotic cell cycle	0.001	0.004	0.014	25	-10000	0	25
STAG2	0.027	0.004	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.013	0.076	-10000	0	-0.55	7	7
spindle elongation	0.02	0.029	0.11	16	-0.097	1	17
ODF2	0.025	0.009	-10000	0	-10000	0	0
BUB1	0.047	0.094	-10000	0	-0.55	7	7
TPT1	0.003	0.052	0.1	1	-0.17	29	30
CDC25C	0.054	0.068	0.18	4	-0.27	12	16
CDC25B	0.03	0.025	0.22	6	-10000	0	6
SGOL1	0.028	0.044	0.18	22	-0.13	3	25
RHOA	0.026	0.006	-10000	0	-10000	0	0
CCNB1/CDK1	0.071	0.072	0.27	6	-10000	0	6
CDC14B	0.006	0.017	-10000	0	-0.34	1	1
CDC20	0.13	0.095	0.22	228	-10000	0	228
PLK1/PBIP1	0.012	0.022	0.1	2	-10000	0	2
mitosis	-0.004	0.008	0.024	2	-0.016	89	91
FBXO5	0.012	0.027	0.11	1	-10000	0	1
CDC2	0.003	0.003	0.012	11	-10000	0	11
NDC80	0.095	0.1	0.23	134	-10000	0	134
metaphase plate congression	0.019	0.032	-10000	0	-0.25	4	4
ERCC6L	0.041	0.055	0.21	8	-10000	0	8
NLP/gamma Tubulin	0.013	0.018	0.076	7	-0.067	1	8
microtubule cytoskeleton organization	0.003	0.052	0.1	1	-0.17	29	30
G2/M transition DNA damage checkpoint	-0.001	0.002	0.014	2	-10000	0	2
PPP1R12A	0.028	0.005	-10000	0	-10000	0	0
interphase	-0.001	0.002	0.014	2	-10000	0	2
PLK1/PRC1-2	0.15	0.097	0.22	197	-0.14	2	199
GRASP65/GM130/RAB1/GTP/PLK1	0.051	0.031	-10000	0	-10000	0	0
RAB1A	0.027	0.005	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.017	0.027	0.094	26	-0.069	1	27
mitotic prometaphase	0	0.002	0.018	4	-10000	0	4
proteasomal ubiquitin-dependent protein catabolic process	0.028	0.063	-10000	0	-0.32	7	7
microtubule-based process	0.12	0.07	0.16	276	-0.12	1	277
Golgi organization	0.02	0.029	0.11	16	-0.097	1	17
Cohesin/SA2	0.031	0.025	0.12	1	-10000	0	1
PPP1CB/MYPT1	0.04	0.011	-10000	0	-10000	0	0
KIF20A	0.16	0.085	0.21	289	-10000	0	289
APC/C/CDC20	0.11	0.074	0.17	225	-0.12	1	226
PPP2R1A	0.027	0.006	-10000	0	-10000	0	0
chromosome segregation	0.011	0.022	0.1	2	-10000	0	2
PRC1	0.063	0.074	0.21	77	-10000	0	77
ECT2	0.027	0.06	0.23	27	-10000	0	27
C13orf34	0.017	0.026	0.091	19	-0.079	1	20
NUDC	0.019	0.032	-10000	0	-0.25	4	4
regulation of attachment of spindle microtubules to kinetochore	0.026	0.041	0.14	10	-0.16	6	16
spindle assembly	0.016	0.025	0.092	17	-0.081	1	18
spindle stabilization	0.017	0.029	0.11	15	-0.16	4	19
APC/C/HCDH1	0.022	0.018	-10000	0	-0.28	1	1
MKLP2/PLK1	0.12	0.07	0.17	276	-0.12	1	277
CCNB1	0.094	0.092	0.22	143	-10000	0	143
PPP1CB	0.028	0.006	-10000	0	-10000	0	0
BTRC	0.027	0.005	-10000	0	-10000	0	0
ROCK2	0.017	0.069	0.19	1	-0.38	9	10
TUBG1	0.016	0.019	0.11	1	-0.18	1	2
G2/M transition of mitotic cell cycle	0.015	0.037	0.17	7	-10000	0	7
MLF1IP	0.006	0.01	-10000	0	-10000	0	0
INCENP	0.028	0.01	0.21	1	-10000	0	1

×

Glucocorticoid receptor regulatory network

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
PCK2	0.053	0.079	-10000	0	-10000	0	0
SMARCC2	0.024	0.021	-10000	0	-10000	0	0
SMARCC1	0.024	0.02	-10000	0	-10000	0	0
TBX21	-0.06	0.18	-10000	0	-0.7	24	24
SUMO2	0.019	0.018	-10000	0	-10000	0	0
STAT1 (dimer)	0.035	0.02	0.22	4	-10000	0	4
FKBP4	0.026	0.006	-10000	0	-10000	0	0
FKBP5	0.007	0.099	-10000	0	-0.47	17	17
GR alpha/HSP90/FKBP51/HSP90	0.068	0.11	0.28	14	-0.28	5	19
PRL	-0.031	0.09	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.12	0.21	0.45	58	-0.36	4	62
RELA	-0.12	0.14	-10000	0	-0.27	135	135
FGG	0.12	0.18	0.39	69	-10000	0	69
GR beta/TIF2	0.05	0.12	0.26	24	-0.31	12	36
IFNG	-0.14	0.23	-10000	0	-0.57	46	46
apoptosis	-0.049	0.18	0.38	2	-0.52	12	14
CREB1	0.032	0.012	-10000	0	-10000	0	0
histone acetylation	-0.079	0.12	-10000	0	-0.35	39	39
BGLAP	-0.04	0.1	-10000	0	-0.41	2	2
GR/PKAc	0.075	0.099	0.29	9	-0.23	1	10
NF kappa B1 p50/RelA	-0.21	0.25	-10000	0	-0.42	217	217
SMARCD1	0.024	0.022	-10000	0	-0.12	1	1
MDM2	0.066	0.083	0.19	77	-10000	0	77
GATA3	0	0.12	0.33	2	-0.46	24	26
AKT1	0.022	0.005	-10000	0	-10000	0	0
CSF2	-0.057	0.098	-10000	0	-0.41	8	8
GSK3B	0.019	0.018	-10000	0	-10000	0	0
NR1I3	-0.012	0.18	0.48	1	-0.53	2	3
CSN2	0.09	0.15	0.33	62	-10000	0	62
BRG1/BAF155/BAF170/BAF60A	0.059	0.062	-10000	0	-0.25	13	13
NFATC1	0.004	0.1	-10000	0	-0.47	18	18
POU2F1	0.027	0.011	-10000	0	-10000	0	0
CDKN1A	0.01	0.12	0.75	1	-1.3	2	3
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.003	0.006	-10000	0	-10000	0	0
SFN	0.038	0.066	0.21	32	-0.47	3	35
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.086	0.11	0.31	10	-0.27	4	14
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.16	0.36	0.44	2	-0.77	99	101
JUN	-0.07	0.16	0.33	4	-0.4	42	46
IL4	-0.068	0.13	-10000	0	-0.5	17	17
CDK5R1	0.037	0.05	0.24	22	-10000	0	22
PRKACA	0.027	0.003	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.14	0.16	0.22	1	-0.39	88	89
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.08	0.11	0.3	9	-0.27	4	13
cortisol/GR alpha (monomer)	0.16	0.23	0.51	71	-10000	0	71
NCOA2	0	0.11	-10000	0	-0.47	20	20
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.14	0.24	-10000	0	-0.48	127	127
AP-1/NFAT1-c-4	-0.18	0.31	-10000	0	-0.59	102	102
AFP	-0.058	0.14	0.49	1	-10000	0	1
SUV420H1	0.027	0.006	-10000	0	-10000	0	0
IRF1	0.095	0.12	0.36	17	-10000	0	17
TP53	0.037	0.041	-10000	0	-0.51	2	2
PPP5C	0.027	0.004	-10000	0	-10000	0	0
KRT17	-0.19	0.35	-10000	0	-0.96	46	46
KRT14	-0.02	0.18	0.48	4	-1.3	4	8
TBP	0.034	0.008	-10000	0	-10000	0	0
CREBBP	-0.011	0.07	0.31	4	-0.28	16	20
HDAC1	0.026	0.006	-10000	0	-10000	0	0
HDAC2	0.024	0.006	-10000	0	-10000	0	0
AP-1	-0.18	0.31	-10000	0	-0.59	105	105
MAPK14	0.019	0.018	-10000	0	-10000	0	0
MAPK10	-0.024	0.14	-10000	0	-0.47	35	35
MAPK11	0.018	0.018	-10000	0	-10000	0	0
KRT5	-0.37	0.54	-10000	0	-1.2	121	121
interleukin-1 receptor activity	-0.002	0.003	-10000	0	-10000	0	0
NCOA1	0.029	0.006	-10000	0	-10000	0	0
STAT1	0.035	0.02	0.22	4	-10000	0	4
CGA	-0.048	0.1	-10000	0	-0.4	2	2
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.027	0.11	-10000	0	-0.41	11	11
MAPK3	0.018	0.018	-10000	0	-10000	0	0
MAPK1	0.019	0.018	-10000	0	-10000	0	0
ICAM1	-0.2	0.25	-10000	0	-0.57	75	75
NFKB1	-0.12	0.14	-10000	0	-0.26	145	145
MAPK8	-0.057	0.14	0.41	2	-0.33	32	34
MAPK9	0.019	0.017	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.053	0.18	0.39	1	-0.55	12	13
BAX	0.014	0.063	-10000	0	-10000	0	0
POMC	-0.22	0.27	0.5	1	-0.7	40	41
EP300	-0.012	0.065	0.26	3	-0.28	15	18
cortisol/GR alpha (dimer)/p53	0.14	0.2	0.47	54	-10000	0	54
proteasomal ubiquitin-dependent protein catabolic process	0.039	0.065	0.18	32	-10000	0	32
SGK1	-0.033	0.28	-10000	0	-1.3	17	17
IL13	-0.13	0.21	-10000	0	-0.71	17	17
IL6	-0.52	0.56	-10000	0	-1.1	194	194
PRKACG	-0.01	0.015	-10000	0	-10000	0	0
IL5	-0.12	0.18	-10000	0	-0.62	13	13
IL2	-0.16	0.23	-10000	0	-0.61	40	40
CDK5	0.025	0.006	-10000	0	-10000	0	0
PRKACB	0.025	0.035	-10000	0	-0.47	2	2
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
IL8	-0.3	0.42	-10000	0	-0.74	144	144
CDK5R1/CDK5	0.042	0.034	0.25	3	-10000	0	3
NF kappa B1 p50/RelA/PKAc	-0.14	0.21	-10000	0	-0.38	137	137
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.14	0.2	0.44	65	-10000	0	65
SMARCA4	0.024	0.021	-10000	0	-10000	0	0
chromatin remodeling	0.084	0.14	0.34	30	-0.42	6	36
NF kappa B1 p50/RelA/Cbp	-0.18	0.22	-10000	0	-0.42	144	144
JUN (dimer)	-0.07	0.16	0.33	4	-0.4	42	46
YWHAH	0.027	0.006	-10000	0	-10000	0	0
VIPR1	-0.05	0.17	0.36	1	-0.64	21	22
NR3C1	0.093	0.14	0.34	50	-10000	0	50
NR4A1	-0.25	0.25	-10000	0	-0.47	224	224
TIF2/SUV420H1	0.016	0.082	-10000	0	-0.34	20	20
MAPKKK cascade	-0.049	0.18	0.38	2	-0.52	12	14
cortisol/GR alpha (dimer)/Src-1	0.14	0.2	0.46	65	-10000	0	65
PBX1	0.006	0.099	-10000	0	-0.46	17	17
POU1F1	0.008	0.028	0.22	3	-10000	0	3
SELE	-0.48	0.54	-10000	0	-1.1	172	172
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.084	0.14	0.34	30	-0.42	6	36
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.14	0.2	0.44	65	-10000	0	65
mol:cortisol	0.079	0.13	0.28	77	-10000	0	77
MMP1	-0.013	0.16	-10000	0	-0.82	9	9

×

LPA4-mediated signaling events

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
ADCY4	-0.004	0.014	-10000	0	-0.28	1	1
ADCY5	-0.13	0.14	-10000	0	-0.28	184	184
ADCY6	-0.004	0.001	-10000	0	-10000	0	0
ADCY7	-0.004	0.001	-10000	0	-10000	0	0
ADCY1	-0.004	0.019	0.24	1	-0.28	1	2
ADCY2	-0.087	0.13	-10000	0	-0.28	120	120
ADCY3	-0.004	0.001	-10000	0	-10000	0	0
ADCY8	-0.007	0.013	0.24	1	-10000	0	1
PRKCE	0.008	0.002	-10000	0	-10000	0	0
ADCY9	-0.008	0.037	-10000	0	-0.28	7	7
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.029	0.11	0.24	24	-0.19	52	76

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.039	0.31	-10000	0	-0.7	37	37
HDAC7	0.029	0.004	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	0.03	0.35	-10000	0	-0.7	38	38
SMAD4	0.027	0.007	-10000	0	-10000	0	0
ID2	-0.025	0.32	-10000	0	-0.72	36	36
AP1	-0.081	0.19	-10000	0	-0.37	120	120
ABCG2	-0.032	0.33	-10000	0	-0.72	39	39
HIF1A	0.01	0.086	-10000	0	-0.21	8	8
TFF3	-0.067	0.37	-10000	0	-0.74	54	54
GATA2	0.026	0.07	0.22	12	-0.47	6	18
AKT1	0.005	0.099	-10000	0	-0.22	18	18
response to hypoxia	-0.011	0.087	-10000	0	-0.19	36	36
MCL1	-0.03	0.3	-10000	0	-0.69	36	36
NDRG1	-0.022	0.31	-10000	0	-0.74	28	28
SERPINE1	-0.025	0.32	-10000	0	-0.71	38	38
FECH	-0.025	0.32	-10000	0	-0.71	36	36
FURIN	-0.024	0.32	-10000	0	-0.7	37	37
NCOA2	0.002	0.11	-10000	0	-0.47	20	20
EP300	0.003	0.13	-10000	0	-0.31	39	39
HMOX1	-0.021	0.32	0.53	1	-0.73	33	34
BHLHE40	-0.025	0.32	-10000	0	-0.7	39	39
BHLHE41	-0.028	0.33	-10000	0	-0.73	37	37
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.059	0.12	-10000	0	-0.34	1	1
ENG	0.035	0.096	0.35	1	-0.3	1	2
JUN	0.011	0.091	-10000	0	-0.47	14	14
RORA	-0.03	0.33	-10000	0	-0.73	38	38
ABCB1	-0.12	0.36	-10000	0	-1	54	54
TFRC	-0.019	0.32	-10000	0	-0.69	36	36
CXCR4	-0.028	0.33	-10000	0	-0.72	40	40
TF	-0.019	0.33	0.53	2	-0.72	38	40
CITED2	-0.023	0.32	-10000	0	-0.72	34	34
HIF1A/ARNT	0.069	0.44	0.73	4	-0.82	30	34
LDHA	-0.025	0.19	-10000	0	-0.67	23	23
ETS1	-0.024	0.32	-10000	0	-0.7	37	37
PGK1	-0.024	0.32	-10000	0	-0.71	36	36
NOS2	-0.023	0.33	-10000	0	-0.74	34	34
ITGB2	-0.025	0.33	-10000	0	-0.72	39	39
ALDOA	-0.021	0.32	-10000	0	-0.71	36	36
Cbp/p300/CITED2	-0.022	0.36	-10000	0	-0.81	42	42
FOS	-0.12	0.23	-10000	0	-0.47	124	124
HK2	-0.02	0.32	-10000	0	-0.72	33	33
SP1	0.014	0.052	-10000	0	-10000	0	0
GCK	-0.045	0.37	-10000	0	-1.3	27	27
HK1	-0.023	0.32	-10000	0	-0.72	35	35
NPM1	-0.024	0.32	-10000	0	-0.7	37	37
EGLN1	-0.023	0.32	-10000	0	-0.7	37	37
CREB1	0.032	0.007	-10000	0	-10000	0	0
PGM1	-0.025	0.32	-10000	0	-0.7	38	38
SMAD3	0.028	0.004	-10000	0	-10000	0	0
EDN1	-0.043	0.21	-10000	0	-0.66	19	19
IGFBP1	-0.017	0.32	-10000	0	-0.7	37	37
VEGFA	0.001	0.28	-10000	0	-0.61	37	37
HIF1A/JAB1	0.028	0.064	-10000	0	-10000	0	0
CP	-0.065	0.37	0.52	1	-0.72	55	56
CXCL12	-0.089	0.39	-10000	0	-0.76	68	68
COPS5	0.026	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4	0.039	0.012	-10000	0	-10000	0	0
BNIP3	-0.028	0.32	-10000	0	-0.7	37	37
EGLN3	-0.029	0.32	-10000	0	-0.72	37	37
CA9	0.01	0.36	0.54	2	-0.73	37	39
TERT	0.011	0.34	0.54	6	-0.73	32	38
ENO1	-0.024	0.32	-10000	0	-0.7	37	37
PFKL	-0.023	0.32	-10000	0	-0.73	33	33
NCOA1	0.027	0.006	-10000	0	-10000	0	0
ADM	-0.026	0.32	-10000	0	-0.71	35	35
ARNT	0.015	0.073	-10000	0	-0.22	1	1
HNF4A	0.035	0.07	0.22	38	-0.18	2	40
ADFP	-0.039	0.31	-10000	0	-0.7	37	37
SLC2A1	0.001	0.28	-10000	0	-0.62	35	35
LEP	-0.043	0.35	-10000	0	-0.74	46	46
HIF1A/ARNT/Cbp/p300	0.018	0.36	-10000	0	-0.72	38	38
EPO	0.019	0.24	0.62	1	-0.69	8	9
CREBBP	0.003	0.13	-10000	0	-0.3	39	39
HIF1A/ARNT/Cbp/p300/HDAC7	0.032	0.35	-10000	0	-0.71	36	36
PFKFB3	-0.031	0.31	-10000	0	-0.7	36	36
NT5E	-0.042	0.35	-10000	0	-0.72	48	48

×

Angiopoietin receptor Tie2-mediated 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
AKT1	-0.038	0.27	-10000	0	-0.81	42	42
NCK1/PAK1/Dok-R	-0.049	0.12	-10000	0	-0.4	42	42
NCK1/Dok-R	-0.049	0.32	-10000	0	-0.95	42	42
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
mol:beta2-estradiol	0.013	0.068	0.24	34	-10000	0	34
RELA	0.027	0.005	-10000	0	-10000	0	0
SHC1	0.027	0.017	0.33	1	-10000	0	1
Rac/GDP	0.02	0.005	-10000	0	-10000	0	0
F2	0.027	0.096	0.25	56	-10000	0	56
TNIP2	0.027	0.005	-10000	0	-10000	0	0
NF kappa B/RelA	-0.022	0.3	-10000	0	-0.89	42	42
FN1	0.025	0.094	0.21	26	-0.47	11	37
PLD2	-0.066	0.31	-10000	0	-0.97	42	42
PTPN11	0.027	0.005	-10000	0	-10000	0	0
GRB14	0.051	0.065	0.21	54	-10000	0	54
ELK1	-0.044	0.29	-10000	0	-0.88	42	42
GRB7	0.028	0.084	0.31	14	-0.47	7	21
PAK1	0.025	0.025	-10000	0	-0.47	1	1
Tie2/Ang1/alpha5/beta1 Integrin	-0.035	0.33	-10000	0	-0.98	42	42
CDKN1A	-0.037	0.2	-10000	0	-0.58	40	40
ITGA5	0.009	0.094	-10000	0	-0.47	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.048	0.32	-10000	0	-0.96	42	42
CRK	0.025	0.008	-10000	0	-10000	0	0
mol:NO	-0.018	0.21	-10000	0	-0.61	42	42
PLG	-0.068	0.31	-10000	0	-0.98	42	42
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.04	0.26	-10000	0	-0.79	42	42
GRB2	0.027	0.005	-10000	0	-10000	0	0
PIK3R1	0.025	0.026	-10000	0	-0.47	1	1
ANGPT2	-0.099	0.21	-10000	0	-0.65	32	32
BMX	-0.11	0.33	-10000	0	-1	42	42
ANGPT1	-0.078	0.34	-10000	0	-1.2	34	34
tube development	-0.051	0.22	-10000	0	-0.62	44	44
ANGPT4	0.022	0.034	0.23	8	-10000	0	8
response to hypoxia	-0.005	0.021	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.038	0.34	-10000	0	-1	42	42
alpha5/beta1 Integrin	0.024	0.071	-10000	0	-0.34	15	15
FGF2	-0.13	0.23	-10000	0	-0.47	127	127
STAT5A (dimer)	-0.048	0.25	-10000	0	-0.7	44	44
mol:L-citrulline	-0.018	0.21	-10000	0	-0.61	42	42
AGTR1	-0.17	0.24	-10000	0	-0.47	161	161
MAPK14	-0.061	0.32	-10000	0	-0.99	42	42
Tie2/SHP2	-0.032	0.22	-10000	0	-0.92	18	18
TEK	-0.022	0.23	-10000	0	-1	18	18
RPS6KB1	-0.035	0.27	-10000	0	-0.79	42	42
Angiotensin II/AT1	-0.12	0.17	-10000	0	-0.33	161	161
Tie2/Ang1/GRB2	-0.05	0.33	-10000	0	-0.99	42	42
MAPK3	-0.057	0.29	-10000	0	-0.89	42	42
MAPK1	-0.059	0.29	-10000	0	-0.9	42	42
Tie2/Ang1/GRB7	-0.051	0.33	-10000	0	-1	42	42
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MAPK8	-0.066	0.31	-10000	0	-0.97	42	42
PI3K	-0.056	0.3	-10000	0	-0.92	42	42
FES	-0.067	0.32	-10000	0	-0.98	43	43
Crk/Dok-R	-0.049	0.32	-10000	0	-0.95	42	42
Tie2/Ang1/ABIN2	-0.051	0.33	-10000	0	-1	42	42
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.029	0.25	-10000	0	-0.73	42	42
STAT5A	0.026	0.025	-10000	0	-0.47	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.026	0.27	0.42	1	-0.78	42	43
Tie2/Ang2	-0.074	0.27	-10000	0	-0.8	44	44
Tie2/Ang1	-0.066	0.34	-10000	0	-1	42	42
FOXO1	-0.025	0.25	-10000	0	-0.73	42	42
ELF1	0.027	0.027	-10000	0	-10000	0	0
ELF2	-0.059	0.31	-10000	0	-0.95	42	42
mol:Choline	-0.061	0.3	-10000	0	-0.93	42	42
cell migration	-0.025	0.074	-10000	0	-0.23	43	43
FYN	-0.06	0.24	-10000	0	-0.7	44	44
DOK2	0.014	0.07	0.21	2	-0.47	8	10
negative regulation of cell cycle	-0.032	0.19	-10000	0	-0.52	40	40
ETS1	0.011	0.076	-10000	0	-0.24	32	32
PXN	-0.014	0.24	0.4	3	-0.65	42	45
ITGB1	0.026	0.006	-10000	0	-10000	0	0
NOS3	-0.026	0.24	-10000	0	-0.69	42	42
RAC1	0.026	0.006	-10000	0	-10000	0	0
TNF	0.02	0.092	0.23	20	-0.25	34	54
MAPKKK cascade	-0.061	0.3	-10000	0	-0.93	42	42
RASA1	0.027	0.006	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.051	0.32	-10000	0	-0.98	42	42
NCK1	0.026	0.006	-10000	0	-10000	0	0
vasculogenesis	-0.013	0.19	-10000	0	-0.55	42	42
mol:Phosphatidic acid	-0.061	0.3	-10000	0	-0.93	42	42
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.018	0.21	-10000	0	-0.61	42	42
Rac1/GTP	-0.032	0.25	-10000	0	-0.74	42	42
MMP2	-0.077	0.33	-10000	0	-1	42	42

×

Coregulation of Androgen receptor activity

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
NRIP1	0.024	0.025	0.33	1	-10000	0	1
SVIL	0.02	0.04	-10000	0	-0.46	2	2
ZNF318	0.031	0.035	0.2	16	-10000	0	16
JMJD2C	0.008	0.012	0.055	1	-10000	0	1
T-DHT/AR/Ubc9	-0.089	0.16	-10000	0	-0.3	146	146
CARM1	0.026	0.009	-10000	0	-10000	0	0
PRDX1	0.028	0.004	-10000	0	-10000	0	0
PELP1	0.026	0.009	-10000	0	-10000	0	0
CTNNB1	0.024	0.018	-10000	0	-10000	0	0
AKT1	0.028	0.01	-10000	0	-10000	0	0
PTK2B	0.021	0.017	-10000	0	-10000	0	0
MED1	0.028	0.012	-10000	0	-10000	0	0
MAK	0.034	0.043	0.21	22	-10000	0	22
response to oxidative stress	0	0.002	-10000	0	-10000	0	0
HIP1	0.021	0.04	-10000	0	-0.47	2	2
GSN	0.018	0.047	-10000	0	-0.47	3	3
NCOA2	-0.001	0.11	-10000	0	-0.47	20	20
NCOA6	0.023	0.026	0.33	1	-10000	0	1
DNA-PK	0.051	0.035	0.22	4	-10000	0	4
NCOA4	0.027	0.006	-10000	0	-10000	0	0
PIAS3	0.022	0.018	-10000	0	-10000	0	0
cell proliferation	-0.004	0.073	0.32	1	-0.43	6	7
XRCC5	0.027	0.009	-10000	0	-10000	0	0
UBE3A	0.022	0.027	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.11	0.18	-10000	0	-0.33	155	155
FHL2	-0.027	0.12	-10000	0	-0.73	6	6
RANBP9	0.023	0.02	-10000	0	-10000	0	0
JMJD1A	-0.016	0.05	0.055	1	-0.12	68	69
CDK6	0.015	0.077	-10000	0	-0.47	10	10
TGFB1I1	0.008	0.09	-10000	0	-0.47	13	13
T-DHT/AR/CyclinD1	-0.085	0.16	0.2	2	-0.3	134	136
XRCC6	0.028	0.009	-10000	0	-10000	0	0
T-DHT/AR	-0.09	0.18	-10000	0	-0.29	170	170
CTDSP1	0.024	0.012	-10000	0	-10000	0	0
CTDSP2	0.03	0.02	-10000	0	-10000	0	0
BRCA1	0.024	0.023	0.22	1	-10000	0	1
TCF4	0.021	0.062	-10000	0	-0.47	6	6
CDKN2A	0.11	0.11	0.22	190	-10000	0	190
SRF	0.033	0.018	-10000	0	-0.15	1	1
NKX3-1	-0.072	0.11	-10000	0	-0.18	170	170
KLK3	-0.045	0.28	-10000	0	-1.4	16	16
TMF1	0.024	0.011	-10000	0	-10000	0	0
HNRNPA1	0.029	0.011	-10000	0	-10000	0	0
AOF2	-0.002	0.015	-10000	0	-0.076	16	16
APPL1	0.016	0.019	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.087	0.16	-10000	0	-0.3	144	144
AR	-0.16	0.24	-10000	0	-0.48	145	145
UBA3	0.024	0.013	-10000	0	-10000	0	0
PATZ1	0.028	0.012	-10000	0	-10000	0	0
PAWR	0.025	0.026	-10000	0	-0.47	1	1
PRKDC	0.026	0.011	-10000	0	-10000	0	0
PA2G4	0.029	0.015	-10000	0	-10000	0	0
UBE2I	0.027	0.006	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.075	0.15	-10000	0	-0.27	144	144
RPS6KA3	0.024	0.021	-10000	0	-10000	0	0
T-DHT/AR/ARA70	-0.088	0.16	-10000	0	-0.3	145	145
LATS2	0.027	0.028	-10000	0	-0.47	1	1
T-DHT/AR/PRX1	-0.076	0.15	0.15	2	-0.27	144	146
Cyclin D3/CDK11 p58	0.02	0.004	-10000	0	-10000	0	0
VAV3	0.023	0.05	0.21	4	-0.46	3	7
KLK2	-0.031	0.079	-10000	0	-0.42	2	2
CASP8	0.027	0.007	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.081	0.16	-10000	0	-0.29	142	142
TMPRSS2	-0.18	0.37	-10000	0	-0.94	73	73
CCND1	0.024	0.087	0.32	14	-0.47	7	21
PIAS1	0.023	0.027	-10000	0	-10000	0	0
mol:T-DHT	-0.005	0.019	-10000	0	-0.051	44	44
CDC2L1	0	0.001	-10000	0	-10000	0	0
PIAS4	0.021	0.037	-10000	0	-0.18	12	12
T-DHT/AR/CDK6	-0.094	0.17	-10000	0	-0.31	149	149
CMTM2	0.029	0.022	0.21	5	-10000	0	5
SNURF	-0.012	0.12	-10000	0	-0.47	27	27
ZMIZ1	0.017	0.031	-10000	0	-10000	0	0
CCND3	0.027	0.005	-10000	0	-10000	0	0
TGIF1	0.027	0.013	-10000	0	-10000	0	0
FKBP4	0.023	0.021	-10000	0	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.027	0.005	-10000	0	-10000	0	0
CCL5	0.011	0.11	0.21	13	-0.47	18	31
SDCBP	0.025	0.008	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	0.037	0.1	0.29	16	-0.28	12	28
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	0.04	0.094	0.26	12	-0.39	4	16
Syndecan-1/Syntenin	0.043	0.096	0.28	12	-0.39	4	16
MAPK3	0.041	0.091	0.27	14	-0.35	4	18
HGF/MET	-0.037	0.16	0.24	2	-0.34	86	88
TGFB1/TGF beta receptor Type II	0.027	0.005	-10000	0	-10000	0	0
BSG	0.027	0.005	-10000	0	-10000	0	0
keratinocyte migration	0.04	0.093	0.26	12	-0.38	4	16
Syndecan-1/RANTES	0.038	0.12	0.28	16	-0.41	11	27
Syndecan-1/CD147	0.059	0.1	0.28	14	-0.36	4	18
Syndecan-1/Syntenin/PIP2	0.038	0.09	0.25	11	-0.38	4	15
LAMA5	0.026	0.007	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.037	0.088	0.24	11	-0.37	4	15
MMP7	0.039	0.14	0.22	78	-0.47	20	98
HGF	-0.076	0.2	0.21	7	-0.47	86	93
Syndecan-1/CASK	0.028	0.093	0.26	13	-0.26	12	25
Syndecan-1/HGF/MET	0.008	0.16	0.28	14	-0.4	21	35
regulation of cell adhesion	0.032	0.087	0.26	14	-0.37	3	17
HPSE	0.04	0.07	0.22	36	-0.47	3	39
positive regulation of cell migration	0.037	0.1	0.29	16	-0.28	12	28
SDC1	0.037	0.1	0.3	14	-0.26	16	30
Syndecan-1/Collagen	0.037	0.1	0.29	16	-0.28	12	28
PPIB	0.027	0.004	-10000	0	-10000	0	0
MET	0.029	0.022	0.33	2	-10000	0	2
PRKACA	0.027	0.003	-10000	0	-10000	0	0
MMP9	0.068	0.1	0.22	102	-0.47	5	107
MAPK1	0.041	0.092	0.27	14	-0.38	3	17
homophilic cell adhesion	0.038	0.1	0.3	17	-0.28	12	29
MMP1	0.13	0.1	0.22	222	-0.47	1	223

×

BCR signaling 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
JUN	-0.051	0.16	0.25	3	-0.4	44	47
IKBKB	-0.018	0.1	-10000	0	-0.31	19	19
AKT1	-0.04	0.11	0.23	11	-0.23	54	65
IKBKG	-0.012	0.1	0.22	1	-0.31	22	23
CALM1	-0.036	0.14	-10000	0	-0.43	29	29
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
MAP3K1	-0.076	0.22	-10000	0	-0.53	54	54
MAP3K7	0.026	0.006	-10000	0	-10000	0	0
mol:Ca2+	-0.037	0.15	-10000	0	-0.42	35	35
DOK1	0.027	0.011	0.21	1	-10000	0	1
AP-1	-0.046	0.11	0.22	2	-0.26	32	34
LYN	0.025	0.008	-10000	0	-10000	0	0
BLNK	0.011	0.087	-10000	0	-0.47	13	13
SHC1	0.026	0.017	0.33	1	-10000	0	1
BCR complex	-0.026	0.17	0.3	7	-0.37	69	76
CD22	-0.1	0.25	-10000	0	-0.55	75	75
CAMK2G	-0.029	0.13	-10000	0	-0.42	26	26
CSNK2A1	0.026	0.006	-10000	0	-10000	0	0
INPP5D	0.018	0.06	-10000	0	-0.47	6	6
SHC/GRB2/SOS1	-0.019	0.11	-10000	0	-0.27	50	50
GO:0007205	-0.039	0.15	-10000	0	-0.43	36	36
SYK	0.02	0.049	-10000	0	-0.47	4	4
ELK1	-0.035	0.15	0.35	1	-0.44	30	31
NFATC1	-0.091	0.22	0.22	4	-0.48	72	76
B-cell antigen/BCR complex	-0.026	0.17	0.3	7	-0.37	69	76
PAG1/CSK	0.035	0.015	-10000	0	-10000	0	0
NFKBIB	0.011	0.043	-10000	0	-0.13	4	4
HRAS	-0.037	0.14	0.26	1	-0.41	33	34
NFKBIA	0.012	0.042	-10000	0	-0.13	3	3
NF-kappa-B/RelA/I kappa B beta	0.017	0.037	-10000	0	-10000	0	0
RasGAP/Csk	-0.001	0.16	0.29	6	-0.33	66	72
mol:GDP	-0.038	0.15	-10000	0	-0.43	32	32
PTEN	0.026	0.007	-10000	0	-10000	0	0
CD79B	0.011	0.097	0.21	7	-0.47	15	22
NF-kappa-B/RelA/I kappa B alpha	0.017	0.037	-10000	0	-10000	0	0
GRB2	0.027	0.005	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.098	0.22	-10000	0	-0.51	66	66
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
mol:IP3	-0.04	0.15	-10000	0	-0.43	36	36
CSK	0.027	0.004	-10000	0	-10000	0	0
FOS	-0.097	0.17	-10000	0	-0.4	60	60
CHUK	-0.02	0.11	-10000	0	-0.32	32	32
IBTK	0.026	0.006	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.01	0.14	0.27	1	-0.4	26	27
PTPN6	-0.1	0.23	-10000	0	-0.53	73	73
RELA	0.027	0.005	-10000	0	-10000	0	0
BCL2A1	0.011	0.034	-10000	0	-10000	0	0
VAV2	-0.1	0.24	-10000	0	-0.56	68	68
ubiquitin-dependent protein catabolic process	0.015	0.042	-10000	0	-0.13	3	3
BTK	-0.042	0.26	-10000	0	-1.1	24	24
CD19	-0.096	0.23	-10000	0	-0.56	59	59
MAP4K1	0.015	0.079	0.21	3	-0.47	10	13
CD72	0.031	0.034	0.21	13	-10000	0	13
PAG1	0.024	0.01	-10000	0	-10000	0	0
MAPK14	-0.062	0.19	0.25	1	-0.45	52	53
SH3BP5	0.025	0.026	-10000	0	-0.47	1	1
PIK3AP1	-0.044	0.17	-10000	0	-0.52	30	30
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.071	0.24	-10000	0	-0.52	67	67
RAF1	-0.016	0.14	0.26	9	-0.4	26	35
RasGAP/p62DOK/SHIP	-0.004	0.16	0.26	7	-0.34	65	72
CD79A	-0.051	0.19	0.21	14	-0.47	69	83
re-entry into mitotic cell cycle	-0.046	0.11	0.22	2	-0.26	29	31
RASA1	0.027	0.006	-10000	0	-10000	0	0
MAPK3	-0.006	0.12	0.27	8	-0.4	16	24
MAPK1	-0.008	0.12	0.28	11	-0.39	17	28
CD72/SHP1	-0.069	0.24	0.31	7	-0.52	64	71
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MAPK8	-0.062	0.19	0.31	4	-0.45	54	58
actin cytoskeleton organization	-0.087	0.21	0.27	4	-0.49	61	65
NF-kappa-B/RelA	0.037	0.071	-10000	0	-10000	0	0
Calcineurin	-0.014	0.13	-10000	0	-0.4	23	23
PI3K	-0.1	0.18	-10000	0	-0.42	80	80
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.041	0.16	-10000	0	-0.42	42	42
SOS1	0.027	0.005	-10000	0	-10000	0	0
Bam32/HPK1	-0.076	0.27	-10000	0	-0.72	49	49
DAPP1	-0.096	0.29	-10000	0	-0.82	47	47
cytokine secretion	-0.083	0.2	0.22	4	-0.44	72	76
mol:DAG	-0.04	0.15	-10000	0	-0.43	36	36
PLCG2	0.026	0.039	0.21	3	-0.47	2	5
MAP2K1	-0.013	0.13	0.26	8	-0.42	19	27
B-cell antigen/BCR complex/FcgammaRIIB	-0.023	0.18	0.29	7	-0.38	66	73
mol:PI-3-4-5-P3	-0.074	0.13	0.26	1	-0.31	69	70
ETS1	-0.025	0.12	0.26	1	-0.43	19	20
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.002	0.15	0.29	7	-0.29	72	79
B-cell antigen/BCR complex/LYN	-0.068	0.22	-10000	0	-0.49	65	65
MALT1	0.026	0.007	-10000	0	-10000	0	0
TRAF6	0.026	0.008	-10000	0	-10000	0	0
RAC1	-0.093	0.22	0.28	3	-0.53	60	63
B-cell antigen/BCR complex/LYN/SYK	-0.068	0.24	-10000	0	-0.53	65	65
CARD11	-0.033	0.15	0.3	1	-0.43	33	34
FCGR2B	-0.004	0.12	0.25	3	-0.47	24	27
PPP3CA	0.027	0.004	-10000	0	-10000	0	0
BCL10	0.027	0.004	-10000	0	-10000	0	0
IKK complex	0.001	0.052	0.16	4	-0.13	16	20
PTPRC	-0.026	0.16	0.21	2	-0.47	44	46
PDPK1	-0.043	0.1	0.22	11	-0.22	60	71
PPP3CB	0.027	0.006	-10000	0	-10000	0	0
PPP3CC	0.023	0.01	-10000	0	-10000	0	0
POU2F2	0.013	0.032	0.13	3	-10000	0	3

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.014	0.093	-10000	0	-0.24	43	43
NF kappa B1 p50/RelA/I kappa B alpha	0.031	0.097	0.31	9	-10000	0	9
alphaV/beta3 Integrin/Osteopontin/Src	0.094	0.07	-10000	0	-10000	0	0
AP1	-0.066	0.2	-10000	0	-0.49	44	44
ILK	-0.014	0.094	-10000	0	-0.25	43	43
bone resorption	0.003	0.1	0.32	1	-0.34	9	10
PTK2B	0.023	0.01	-10000	0	-10000	0	0
PYK2/p130Cas	0.064	0.13	0.29	3	-0.23	33	36
ITGAV	0.03	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.021	0.076	0.24	1	-0.33	17	18
alphaV/beta3 Integrin/Osteopontin	0.068	0.14	-10000	0	-0.28	43	43
MAP3K1	-0.014	0.095	0.2	3	-0.26	43	46
JUN	0.01	0.091	-10000	0	-0.47	14	14
MAPK3	-0.013	0.084	0.2	9	-0.24	40	49
MAPK1	-0.013	0.087	0.2	9	-0.24	42	51
Rac1/GDP	0.02	0.005	-10000	0	-10000	0	0
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MAPK8	-0.021	0.089	0.2	10	-0.25	43	53
ITGB3	-0.024	0.15	-10000	0	-0.46	44	44
NFKBIA	-0.006	0.082	0.26	2	-0.25	11	13
FOS	-0.12	0.23	-10000	0	-0.47	124	124
CD44	0.013	0.082	0.33	1	-0.47	11	12
CHUK	0.027	0.005	-10000	0	-10000	0	0
PLAU	0.008	0.098	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.045	0.093	0.32	1	-10000	0	1
BCAR1	0.026	0.006	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.004	0.12	-10000	0	-0.33	44	44
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.017	0.094	0.2	9	-0.25	46	55
VAV3	-0.024	0.088	0.19	14	-0.24	47	61
MAP3K14	-0.012	0.094	0.2	8	-0.26	43	51
ROCK2	0.018	0.065	-10000	0	-0.47	7	7
SPP1	0.1	0.092	0.22	161	-10000	0	161
RAC1	0.026	0.006	-10000	0	-10000	0	0
Rac1/GTP	-0.014	0.085	-10000	0	-0.22	45	45
MMP2	-0.097	0.18	-10000	0	-0.5	51	51

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.009	0.095	0.17	25	-0.29	30	55
EPHB2	0.04	0.047	0.21	28	-10000	0	28
Syndecan-2/TACI	-0.01	0.1	0.16	7	-0.29	44	51
LAMA1	0.04	0.12	0.22	66	-0.47	14	80
Syndecan-2/alpha2 ITGB1	0.022	0.11	0.27	6	-0.26	41	47
HRAS	0.025	0.008	-10000	0	-10000	0	0
Syndecan-2/CASK	-0.008	0.067	-10000	0	-0.28	24	24
ITGA5	0.009	0.094	-10000	0	-0.47	15	15
BAX	-0.007	0.058	-10000	0	-10000	0	0
EPB41	0.028	0.002	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.007	0.064	-10000	0	-0.25	23	23
LAMA3	0.003	0.15	0.22	35	-0.47	32	67
EZR	0.027	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.022	0.049	-10000	0	-0.47	4	4
Syndecan-2/MMP2	-0.011	0.11	-10000	0	-0.34	39	39
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.038	0.027	0.24	1	-0.34	1	2
dendrite morphogenesis	0.017	0.085	0.18	26	-0.28	24	50
Syndecan-2/GM-CSF	0.031	0.1	0.17	71	-0.28	24	95
determination of left/right symmetry	-0.009	0.08	-10000	0	-0.33	24	24
Syndecan-2/PKC delta	0.007	0.07	-10000	0	-0.27	23	23
GNB2L1	0.026	0.006	-10000	0	-10000	0	0
MAPK3	0.031	0.093	0.2	60	-0.26	21	81
MAPK1	0.031	0.097	0.2	63	-0.26	24	87
Syndecan-2/RACK1	0.017	0.065	-10000	0	-0.23	24	24
NF1	0.026	0.006	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	-0.009	0.08	-10000	0	-0.33	24	24
ITGA2	0.028	0.035	0.24	5	-0.47	1	6
MAPK8	-0.006	0.067	-10000	0	-0.27	24	24
Syndecan-2/alpha2/beta1 Integrin	0.038	0.1	0.26	9	-0.25	31	40
Syndecan-2/Kininogen	0.002	0.067	-10000	0	-0.28	21	21
ITGB1	0.026	0.006	-10000	0	-10000	0	0
SRC	0.023	0.084	0.19	49	-0.22	24	73
Syndecan-2/CASK/Protein 4.1	0.007	0.065	-10000	0	-0.25	24	24
extracellular matrix organization	0.007	0.072	-10000	0	-0.28	24	24
actin cytoskeleton reorganization	0.009	0.094	0.17	25	-0.29	30	55
Syndecan-2/Caveolin-2/Ras	0.016	0.075	-10000	0	-0.26	26	26
Syndecan-2/Laminin alpha3	0.002	0.11	0.17	34	-0.29	43	77
Syndecan-2/RasGAP	0.026	0.067	-10000	0	-0.22	24	24
alpha5/beta1 Integrin	0.024	0.071	-10000	0	-0.34	15	15
PRKCD	0.026	0.007	-10000	0	-10000	0	0
Syndecan-2 dimer	0.017	0.085	0.18	26	-0.28	24	50
GO:0007205	0.003	0.001	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.014	0.061	-10000	0	-0.22	24	24
RHOA	0.026	0.006	-10000	0	-10000	0	0
SDCBP	0.025	0.008	-10000	0	-10000	0	0
TNFRSF13B	-0.013	0.13	0.21	7	-0.47	28	35
RASA1	0.027	0.006	-10000	0	-10000	0	0
alpha2/beta1 Integrin	0.038	0.027	0.24	1	-0.34	1	2
Syndecan-2/Synbindin	0.006	0.072	-10000	0	-0.27	24	24
TGFB1	0.027	0.005	-10000	0	-10000	0	0
CASP3	0.028	0.09	0.2	58	-0.25	21	79
FN1	0.025	0.094	0.21	26	-0.47	11	37
Syndecan-2/IL8	-0.024	0.12	0.16	1	-0.3	61	62
SDC2	-0.009	0.08	-10000	0	-0.33	24	24
KNG1	-0.016	0.004	-10000	0	-10000	0	0
Syndecan-2/Neurofibromin	0.006	0.072	-10000	0	-0.28	24	24
TRAPPC4	0.026	0.007	-10000	0	-10000	0	0
CSF2	0.056	0.075	0.21	74	-10000	0	74
Syndecan-2/TGFB1	0.007	0.072	-10000	0	-0.28	24	24
Syndecan-2/Syntenin/PI-4-5-P2	0.007	0.064	-10000	0	-0.25	23	23
Syndecan-2/Ezrin	0.02	0.069	-10000	0	-0.25	23	23
PRKACA	0.028	0.095	0.2	61	-0.25	24	85
angiogenesis	-0.024	0.12	0.16	1	-0.3	61	62
MMP2	-0.011	0.13	-10000	0	-0.47	31	31
IL8	-0.041	0.17	0.21	1	-0.47	56	57
calcineurin-NFAT signaling pathway	-0.01	0.1	0.16	7	-0.29	44	51

×

Arf6 signaling events

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
CENTA1/KIF3B	0.027	0.03	-10000	0	-0.28	3	3
ARNO/beta Arrestin1-2	0.004	0.097	-10000	0	-0.78	2	2
EGFR	0.021	0.085	0.33	8	-0.47	9	17
EPHA2	0.021	0.055	-10000	0	-0.47	5	5
USP6	0.025	0.008	-10000	0	-10000	0	0
IQSEC1	0.025	0.018	0.33	1	-10000	0	1
EGFR/EGFR/EGF/EGF	0.04	0.071	0.24	7	-0.34	9	16
ARRB2	0.01	0.006	-10000	0	-10000	0	0
mol:GTP	0.019	0.049	0.14	33	-0.16	6	39
ARRB1	0.021	0.049	-10000	0	-0.47	4	4
FBXO8	0.026	0.006	-10000	0	-10000	0	0
TSHR	0.019	0.032	0.21	7	-10000	0	7
EGF	0.034	0.047	0.21	24	-10000	0	24
somatostatin receptor activity	0	0	0	9	-0.001	80	89
ARAP2	0.024	0.035	-10000	0	-0.47	2	2
mol:GDP	-0.068	0.14	0.21	2	-0.28	88	90
mol:PI-3-4-5-P3	0	0	0.001	3	-0.001	46	49
ITGA2B	0.04	0.052	0.22	31	-10000	0	31
ARF6	0.027	0.005	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.059	0.047	0.24	5	-0.26	4	9
ADAP1	0.023	0.043	-10000	0	-0.47	3	3
KIF13B	0.023	0.01	-10000	0	-10000	0	0
HGF/MET	-0.037	0.16	0.24	2	-0.34	86	88
PXN	0.027	0.004	-10000	0	-10000	0	0
ARF6/GTP	-0.063	0.13	0.21	6	-0.27	80	86
EGFR/EGFR/EGF/EGF/ARFGEP100	0.05	0.063	0.24	8	-0.28	7	15
ADRB2	-0.034	0.16	-10000	0	-0.47	49	49
receptor agonist activity	0	0	0	5	0	81	86
actin filament binding	0	0	0	7	-0.001	84	91
SRC	0.026	0.007	-10000	0	-10000	0	0
ITGB3	-0.027	0.15	-10000	0	-0.47	44	44
GNAQ	0.025	0.009	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	0.001	12	-0.001	57	69
ARF6/GDP	-0.017	0.15	0.27	8	-0.42	32	40
ARF6/GDP/GULP/ACAP1	-0.077	0.18	-10000	0	-0.36	93	93
alphaIIb/beta3 Integrin/paxillin/GIT1	0.036	0.11	-10000	0	-0.26	42	42
ACAP1	0.015	0.079	0.21	4	-0.47	10	14
ACAP2	0.026	0.007	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0.014	0.023	0.18	2	-10000	0	2
EFNA1	0.031	0.039	0.3	8	-10000	0	8
HGF	-0.076	0.2	0.21	7	-0.47	86	93
CYTH3	0.007	0.002	-10000	0	-10000	0	0
CYTH2	0.014	0.071	-10000	0	-0.99	2	2
NCK1	0.026	0.006	-10000	0	-10000	0	0
fibronectin binding	0	0	0	11	0	59	70
endosomal lumen acidification	0	0	0	23	0	73	96
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	-0.045	0.17	-10000	0	-0.47	59	59
GNAQ/ARNO	0.027	0.067	-10000	0	-0.91	2	2
mol:Phosphatidic acid	0	0	0	1	-10000	0	1
PIP3-E	0	0	0	3	0	13	16
MET	0.029	0.022	0.33	2	-10000	0	2
GNA14	-0.03	0.16	-10000	0	-0.47	45	45
GNA15	0.023	0.043	-10000	0	-0.47	3	3
GIT1	0.026	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	12	-0.001	73	85
GNA11	0.026	0.025	-10000	0	-0.47	1	1
LHCGR	-0.005	0.025	0.21	2	-10000	0	2
AGTR1	-0.17	0.24	-10000	0	-0.47	161	161
desensitization of G-protein coupled receptor protein signaling pathway	0.014	0.023	0.18	2	-10000	0	2
IPCEF1/ARNO	0.042	0.08	-10000	0	-0.83	2	2
alphaIIb/beta3 Integrin	0.006	0.12	-10000	0	-0.34	44	44

×

Aurora C signaling

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.Total.Perturbations
INCENP	0.028	0.01	0.21	1	-9999	1
Aurora C/Aurora B/INCENP	0.094	0.068	0.26	6	-9999	6
metaphase	0	0	-10000	0	-9999	0
mitosis	0	0	-10000	0	-9999	0
H3F3B	0.011	0.006	-10000	0	-9999	0
AURKB	0.11	0.095	0.21	178	-9999	178
AURKC	0.033	0.033	0.21	13	-9999	13

×

Wnt signaling

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
Noncanonical Wnts/FZD	-0.01	0.12	0.35	1	-0.3	48	49
FZD6	0.023	0.011	-10000	0	-10000	0	0
WNT6	0.03	0.096	0.21	36	-0.47	10	46
WNT4	-0.002	0.12	0.21	3	-0.47	25	28
FZD3	0.021	0.036	-10000	0	-0.47	2	2
WNT5A	0.022	0.071	0.21	10	-0.47	7	17
WNT11	0.017	0.12	0.22	33	-0.47	20	53

×

FOXM1 transcription factor network

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
NFATC3	0.076	0.41	0.77	2	-0.97	16	18
PLK1	0.079	0.13	-10000	0	-0.97	4	4
BIRC5	0.1	0.12	-10000	0	-1.1	2	2
HSPA1B	0.074	0.41	0.71	1	-0.98	16	17
MAP2K1	0.042	0.063	-10000	0	-10000	0	0
BRCA2	0.078	0.41	0.85	2	-0.98	16	18
FOXM1	0.068	0.46	0.71	1	-1.1	21	22
XRCC1	0.075	0.41	0.78	3	-0.95	18	21
FOXM1B/p19	-0.014	0.41	-10000	0	-1	25	25
Cyclin D1/CDK4	0.068	0.4	0.67	4	-0.93	18	22
CDC2	0.069	0.42	0.68	1	-0.94	23	24
TGFA	0.063	0.38	0.62	2	-0.87	19	21
SKP2	0.095	0.42	0.76	10	-0.96	16	26
CCNE1	0.065	0.086	0.26	64	-10000	0	64
CKS1B	0.07	0.4	0.63	2	-0.89	23	25
RB1	0.068	0.25	0.46	17	-0.75	12	29
FOXM1C/SP1	0.058	0.44	-10000	0	-1	24	24
AURKB	0.026	0.27	-10000	0	-0.84	30	30
CENPF	0.087	0.41	0.76	1	-0.98	16	17
CDK4	0.033	0.034	0.34	1	-10000	0	1
MYC	0.037	0.39	0.59	2	-0.9	25	27
CHEK2	0.042	0.064	0.32	1	-10000	0	1
ONECUT1	0.068	0.4	0.66	2	-0.91	20	22
CDKN2A	0.095	0.1	0.21	156	-0.26	1	157
LAMA4	0.062	0.43	-10000	0	-1.1	18	18
FOXM1B/HNF6	0.059	0.43	-10000	0	-1.1	19	19
FOS	-0.18	0.65	0.71	2	-1	130	132
SP1	0.027	0.01	-10000	0	-10000	0	0
CDC25B	0.08	0.41	0.78	4	-0.98	16	20
response to radiation	0.02	0.042	-10000	0	-10000	0	0
CENPB	0.08	0.41	0.76	5	-0.98	16	21
CENPA	0.09	0.41	0.71	1	-0.98	16	17
NEK2	0.087	0.41	-10000	0	-0.98	16	16
HIST1H2BA	0.074	0.41	0.74	5	-0.96	18	23
CCNA2	0.08	0.089	0.23	105	-10000	0	105
EP300	0.027	0.006	-10000	0	-10000	0	0
CCNB1/CDK1	0.058	0.44	-10000	0	-1.1	17	17
CCNB2	0.085	0.41	-10000	0	-0.97	16	16
CCNB1	0.072	0.42	-10000	0	-1	17	17
ETV5	0.079	0.41	0.77	4	-1	15	19
ESR1	-0.063	0.58	-10000	0	-1.1	78	78
CCND1	0.045	0.39	0.73	1	-0.96	18	19
GSK3A	0.037	0.054	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	0.11	0.11	0.28	72	-10000	0	72
CDK2	0.03	0.017	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.025	0.051	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	0.056	0.41	-10000	0	-0.98	21	21
GAS1	-0.096	0.64	-10000	0	-1.1	94	94
MMP2	0.016	0.51	-10000	0	-1.2	40	40
RB1/FOXM1C	0.055	0.4	0.66	5	-0.98	18	23
CREBBP	0.026	0.007	-10000	0	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.002	0.12	0.35	40	-10000	0	40
KIRREL	-0.022	0.15	-10000	0	-0.48	40	40
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.002	0.12	-10000	0	-0.35	40	40
PLCG1	0.026	0.007	-10000	0	-10000	0	0
ARRB2	0.025	0.008	-10000	0	-10000	0	0
WASL	0.027	0.004	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.028	0.1	0.24	2	-0.26	40	42
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0	0.078	-10000	0	-0.24	36	36
FYN	-0.005	0.11	0.28	14	-0.26	41	55
mol:Ca2+	0.026	0.099	0.24	2	-0.26	36	38
mol:DAG	0.027	0.1	0.24	2	-0.26	36	38
NPHS2	0.014	0.056	0.23	19	-10000	0	19
mol:IP3	0.027	0.1	0.24	2	-0.26	36	38
regulation of endocytosis	0.016	0.091	-10000	0	-0.24	40	40
Nephrin/NEPH1/podocin/Cholesterol	0.015	0.099	0.22	2	-0.26	40	42
establishment of cell polarity	-0.002	0.12	-10000	0	-0.35	40	40
Nephrin/NEPH1/podocin/NCK1-2	0.039	0.1	-10000	0	-0.24	37	37
Nephrin/NEPH1/beta Arrestin2	0.017	0.093	-10000	0	-0.24	40	40
NPHS1	0.007	0.043	0.23	6	-10000	0	6
Nephrin/NEPH1/podocin	0.015	0.098	-10000	0	-0.26	41	41
TJP1	0.027	0.005	-10000	0	-10000	0	0
NCK1	0.026	0.006	-10000	0	-10000	0	0
NCK2	0.027	0.004	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.028	0.1	0.24	2	-0.26	36	38
CD2AP	0.027	0.003	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.029	0.1	0.24	2	-0.26	38	40
GRB2	0.027	0.005	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.004	0.11	0.29	14	-0.25	40	54
cytoskeleton organization	-0.008	0.088	0.21	7	-0.27	35	42
Nephrin/NEPH1	0.003	0.085	-10000	0	-0.24	40	40
Nephrin/NEPH1/ZO-1	0.014	0.1	-10000	0	-0.28	40	40

×

ErbB2/ErbB3 signaling events

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
USP8	-0.004	0.008	-10000	0	-10000	0	0
RAS family/GTP	-0.002	0.11	0.24	1	-0.29	10	11
NFATC4	-0.031	0.096	0.25	10	-0.26	16	26
ERBB2IP	0.026	0.008	-10000	0	-10000	0	0
HSP90 (dimer)	0.027	0.005	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.025	0.11	0.29	3	-0.26	57	60
JUN	-0.007	0.084	0.22	7	-0.32	1	8
HRAS	0.025	0.008	-10000	0	-10000	0	0
DOCK7	-0.031	0.1	0.29	5	-0.25	57	62
ErbB2/ErbB3/neuregulin 1 beta/SHC	0	0.12	0.23	8	-0.26	53	61
AKT1	0.005	0.007	-10000	0	-10000	0	0
BAD	-0.003	0.005	-10000	0	-10000	0	0
MAPK10	-0.025	0.086	0.19	14	-0.21	23	37
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.026	0.12	0.31	3	-0.27	57	60
RAF1	-0.011	0.095	0.27	3	-0.3	10	13
ErbB2/ErbB3/neuregulin 2	-0.091	0.14	0.2	5	-0.28	147	152
STAT3	0.023	0.063	-10000	0	-0.84	2	2
cell migration	-0.021	0.081	0.22	12	-0.23	10	22
mol:PI-3-4-5-P3	-0.001	0.002	-10000	0	-10000	0	0
cell proliferation	-0.066	0.22	-10000	0	-0.62	24	24
FOS	-0.12	0.26	0.3	1	-0.48	131	132
NRAS	0.027	0.002	-10000	0	-10000	0	0
mol:Ca2+	-0.025	0.11	0.29	3	-0.26	57	60
MAPK3	-0.031	0.17	-10000	0	-0.52	17	17
MAPK1	-0.034	0.17	-10000	0	-0.55	18	18
JAK2	-0.032	0.1	0.29	3	-0.25	54	57
NF2	0.003	0.064	-10000	0	-0.61	4	4
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.013	0.1	0.19	8	-0.25	53	61
NRG1	-0.038	0.18	0.22	18	-0.47	56	74
GRB2/SOS1	0.039	0.01	-10000	0	-10000	0	0
MAPK8	-0.036	0.12	0.25	5	-0.27	54	59
MAPK9	-0.015	0.07	0.2	12	-0.21	2	14
ERBB2	-0.009	0.052	0.27	13	-10000	0	13
ERBB3	0.015	0.08	0.32	2	-0.47	10	12
SHC1	0.026	0.017	0.33	1	-10000	0	1
RAC1	0.026	0.006	-10000	0	-10000	0	0
apoptosis	0.01	0.017	-10000	0	-0.15	1	1
STAT3 (dimer)	0.024	0.062	-10000	0	-0.82	2	2
RNF41	-0.006	0.009	-10000	0	-10000	0	0
FRAP1	-0.002	0.004	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.03	0.069	-10000	0	-0.19	52	52
ErbB2/ErbB2/HSP90 (dimer)	0.008	0.038	0.21	11	-10000	0	11
CHRNA1	-0.016	0.14	-10000	0	-0.41	14	14
myelination	-0.025	0.1	0.26	13	-0.32	6	19
PPP3CB	-0.028	0.099	0.28	5	-0.23	53	58
KRAS	0.027	0.016	0.33	1	-10000	0	1
RAC1-CDC42/GDP	0.008	0.11	0.24	2	-0.25	16	18
NRG2	-0.18	0.24	-10000	0	-0.47	164	164
mol:GDP	-0.013	0.1	0.19	8	-0.25	53	61
SOS1	0.027	0.005	-10000	0	-10000	0	0
MAP2K2	-0.017	0.095	0.26	4	-0.31	10	14
SRC	0.026	0.007	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.031	0.1	0.28	4	-0.25	57	61
MAP2K1	-0.057	0.18	-10000	0	-0.61	12	12
heart morphogenesis	-0.025	0.11	0.29	3	-0.26	57	60
RAS family/GDP	0.01	0.11	0.26	1	-0.29	9	10
GRB2	0.027	0.005	-10000	0	-10000	0	0
PRKACA	0.002	0.073	-10000	0	-0.64	5	5
CHRNE	0.005	0.024	0.11	3	-0.19	1	4
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
activation of caspase activity	-0.005	0.007	-10000	0	-10000	0	0
nervous system development	-0.025	0.11	0.29	3	-0.26	57	60
CDC42	0.028	0.003	-10000	0	-10000	0	0

×

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

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
MET/RANBP9	0.038	0.019	0.24	2	-10000	0	2
CRKL	-0.022	0.14	0.3	4	-0.51	14	18
mol:PIP3	-0.002	0.062	-10000	0	-0.87	2	2
AKT1	-0.004	0.057	-10000	0	-0.76	2	2
PTK2B	0.023	0.01	-10000	0	-10000	0	0
RAPGEF1	-0.021	0.13	0.33	2	-0.51	12	14
RANBP10	0.026	0.006	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
HGF/MET/SHIP2	-0.013	0.14	0.24	2	-0.28	79	81
MAP3K5	-0.017	0.14	0.36	2	-0.44	19	21
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.001	0.13	-10000	0	-0.26	85	85
AP1	-0.077	0.17	-10000	0	-0.32	119	119
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.026	0.017	0.33	1	-10000	0	1
apoptosis	-0.23	0.37	-10000	0	-0.75	133	133
STAT3 (dimer)	-0.03	0.11	-10000	0	-0.24	75	75
GAB1/CRKL/SHP2/PI3K	0.006	0.14	0.39	1	-0.47	13	14
INPP5D	0.018	0.06	-10000	0	-0.47	6	6
CBL/CRK	-0.012	0.13	0.27	2	-0.48	14	16
PTPN11	0.027	0.005	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.026	0.007	-10000	0	-10000	0	0
PTEN	0.026	0.007	-10000	0	-10000	0	0
ELK1	0.003	0.087	0.35	16	-10000	0	16
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.019	0.081	-10000	0	-0.25	20	20
PAK1	0.002	0.067	-10000	0	-0.73	2	2
HGF/MET/RANBP10	-0.015	0.14	0.24	2	-0.28	84	86
HRAS	-0.037	0.14	-10000	0	-0.54	16	16
DOCK1	-0.023	0.13	0.3	6	-0.47	15	21
GAB1	-0.03	0.14	0.26	1	-0.45	21	22
CRK	-0.026	0.14	0.26	3	-0.5	15	18
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.066	0.2	-10000	0	-0.46	74	74
JUN	0.01	0.09	-10000	0	-0.47	14	14
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.032	0.087	0.17	2	-0.19	86	88
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
cell morphogenesis	-0.012	0.14	0.33	14	-0.36	16	30
GRB2/SHC	-0.004	0.091	0.22	1	-0.24	13	14
FOS	-0.12	0.23	-10000	0	-0.47	124	124
GLMN	0.004	0.001	-10000	0	-10000	0	0
cell motility	0.003	0.087	0.35	16	-10000	0	16
HGF/MET/MUC20	-0.03	0.13	-10000	0	-0.28	86	86
cell migration	-0.005	0.088	0.22	1	-0.24	13	14
GRB2	0.027	0.005	-10000	0	-10000	0	0
CBL	0.026	0.007	-10000	0	-10000	0	0
MET/RANBP10	0.039	0.018	0.24	2	-10000	0	2
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.025	0.11	0.18	1	-0.24	75	76
MET/MUC20	0.02	0.003	-10000	0	-10000	0	0
RAP1B	-0.007	0.13	0.36	3	-0.48	12	15
RAP1A	-0.019	0.12	0.39	1	-0.5	11	12
HGF/MET/RANBP9	-0.012	0.13	0.24	2	-0.28	75	77
RAF1	-0.016	0.15	-10000	0	-0.51	14	14
STAT3	-0.031	0.11	-10000	0	-0.24	75	75
cell proliferation	-0.033	0.16	0.27	7	-0.33	67	74
RPS6KB1	-0.001	0.034	-10000	0	-10000	0	0
MAPK3	-0.004	0.092	0.66	5	-10000	0	5
MAPK1	-0.001	0.11	0.7	7	-10000	0	7
RANBP9	0.026	0.008	-10000	0	-10000	0	0
MAPK8	-0.006	0.13	0.3	5	-0.47	13	18
SRC	-0.028	0.098	0.16	1	-0.23	71	72
PI3K	-0.005	0.092	-10000	0	-0.24	16	16
MET/Glomulin	0.019	0.029	0.24	2	-10000	0	2
SOS1	0.027	0.005	-10000	0	-10000	0	0
MAP2K1	-0.01	0.15	0.31	1	-0.48	14	15
MET	0.029	0.022	0.33	2	-10000	0	2
MAP4K1	-0.021	0.15	0.38	1	-0.48	18	19
PTK2	0.025	0.009	-10000	0	-10000	0	0
MAP2K2	-0.009	0.15	0.31	2	-0.48	14	16
BAD	-0.003	0.06	0.38	1	-0.73	2	3
MAP2K4	-0.012	0.12	0.31	4	-0.43	15	19
SHP2/GRB2/SOS1/GAB1	-0.006	0.12	-10000	0	-0.47	12	12
INPPL1	0.026	0.006	-10000	0	-10000	0	0
PXN	0.027	0.004	-10000	0	-10000	0	0
SH3KBP1	0.027	0.005	-10000	0	-10000	0	0
HGS	-0.031	0.078	0.15	2	-0.18	82	84
PLCgamma1/PKC	0.019	0.005	-10000	0	-10000	0	0
HGF	-0.076	0.2	0.21	7	-0.47	86	93
RASA1	0.027	0.006	-10000	0	-10000	0	0
NCK1	0.026	0.006	-10000	0	-10000	0	0
PTPRJ	0.026	0.007	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.004	0.096	-10000	0	-0.2	74	74
PDPK1	-0.004	0.058	-10000	0	-0.81	2	2
HGF/MET/SHIP	-0.022	0.15	0.24	2	-0.29	88	90

×

FAS signaling pathway (CD95)

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
SPTAN1	-0.004	0.044	0.21	11	-0.19	8	19
RFC1	-0.003	0.05	0.2	15	-0.19	9	24
PRKDC	0.012	0.077	0.22	41	-0.19	9	50
RIPK1	0.03	0.009	-10000	0	-10000	0	0
CASP7	-0.03	0.14	-10000	0	-0.68	14	14
FASLG/FAS/FADD/FAF1	-0.019	0.074	0.22	5	-0.28	16	21
MAP2K4	-0.11	0.19	-10000	0	-0.43	59	59
mol:ceramide	-0.046	0.12	-10000	0	-0.36	22	22
GSN	-0.005	0.047	0.21	11	-0.2	9	20
FASLG/FAS/FADD/FAF1/Caspase 8	-0.029	0.095	0.21	1	-0.34	17	18
FAS	0	0.059	-10000	0	-0.48	5	5
BID	-0.015	0.035	0.25	6	-10000	0	6
MAP3K1	-0.057	0.14	0.26	1	-0.46	22	23
MAP3K7	0.022	0.009	-10000	0	-10000	0	0
RB1	-0.003	0.058	0.22	14	-0.44	1	15
CFLAR	0.031	0.008	-10000	0	-10000	0	0
HGF/MET	-0.022	0.14	0.24	2	-0.29	90	92
ARHGDIB	0	0.057	0.22	19	-0.19	9	28
FADD	0.01	0.046	0.32	6	-10000	0	6
actin filament polymerization	0.006	0.049	0.27	1	-0.21	10	11
NFKB1	-0.064	0.13	-10000	0	-0.53	9	9
MAPK8	-0.19	0.27	0.31	2	-0.48	174	176
DFFA	-0.004	0.052	0.22	14	-0.19	10	24
DNA fragmentation during apoptosis	-0.004	0.057	0.23	14	-10000	0	14
FAS/FADD/MET	0.019	0.06	0.24	6	-0.3	5	11
CFLAR/RIP1	0.044	0.017	-10000	0	-10000	0	0
FAIM3	0.026	0.053	0.21	4	-0.47	4	8
FAF1	0.002	0.03	-10000	0	-10000	0	0
PARP1	-0.004	0.049	0.2	14	-0.19	10	24
DFFB	-0.003	0.054	0.22	13	-10000	0	13
CHUK	-0.057	0.11	-10000	0	-0.58	5	5
FASLG	-0.013	0.099	0.2	7	-0.48	15	22
FAS/FADD	0.007	0.058	0.24	4	-0.35	5	9
HGF	-0.076	0.2	0.21	7	-0.47	86	93
LMNA	0.005	0.066	0.21	28	-10000	0	28
CASP6	-0.003	0.049	0.2	15	-0.19	4	19
CASP10	0.005	0.027	-10000	0	-10000	0	0
CASP3	0.003	0.048	0.25	14	-10000	0	14
PTPN13	0.018	0.065	-10000	0	-0.47	7	7
CASP8	-0.019	0.039	0.35	4	-10000	0	4
IL6	-0.53	0.64	-10000	0	-1.2	182	182
MET	0.029	0.022	0.33	2	-10000	0	2
ICAD/CAD	-0.002	0.052	0.36	3	-10000	0	3
FASLG/FAS/FADD/FAF1/Caspase 10	-0.047	0.12	-10000	0	-0.37	22	22
activation of caspase activity by cytochrome c	-0.015	0.035	0.25	6	-10000	0	6
PAK2	0.005	0.063	0.21	29	-0.19	5	34
BCL2	0.009	0.093	-10000	0	-0.47	15	15

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.042	0.04	0.21	1	-0.24	6	7
RGS9BP	0.01	0.091	0.29	3	-0.47	13	16
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	-0.012	0.017	0.21	1	-10000	0	1
mol:Na +	0.023	0.1	-10000	0	-0.29	32	32
mol:ADP	-0.011	0.017	0.29	1	-10000	0	1
GNAT2	0.021	0.029	0.24	4	-10000	0	4
RGS9-1/Gbeta5/R9AP	-0.028	0.15	0.24	2	-0.29	91	93
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.03	0.015	-10000	0	-10000	0	0
GRK7	0.019	0.024	0.33	1	-10000	0	1
CNGB3	0.078	0.098	0.24	108	-10000	0	108
Cone Metarhodopsin II/X-Arrestin	0.013	0.004	-10000	0	-10000	0	0
mol:Ca2+	0.004	0.1	0.2	43	-0.27	31	74
Cone PDE6	-0.013	0.14	-10000	0	-0.26	89	89
Cone Metarhodopsin II	0.026	0.014	0.2	1	-10000	0	1
Na + (4 Units)	0.035	0.11	0.24	26	-0.27	31	57
GNAT2/GDP	-0.013	0.13	0.22	2	-0.25	91	93
GNB5	0.027	0.004	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.007	0.031	0.18	10	-10000	0	10
Cone Transducin	0.045	0.042	0.22	1	-0.26	6	7
SLC24A2	0.023	0.051	0.22	22	-10000	0	22
GNB3/GNGT2	0.033	0.047	-10000	0	-0.34	6	6
GNB3	0.023	0.044	0.21	1	-0.47	3	4
GNAT2/GTP	0.02	0.012	0.15	3	-10000	0	3
CNGA3	-0.035	0.14	-10000	0	-0.47	39	39
ARR3	-0.009	0.018	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.023	0.11	-10000	0	-0.29	32	32
mol:Pi	-0.028	0.14	0.23	2	-0.29	91	93
Cone CNG Channel	0.042	0.1	-10000	0	-0.25	32	32
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.023	0.051	0.22	22	-10000	0	22
RGS9	-0.077	0.2	-10000	0	-0.47	84	84
PDE6C	-0.008	0.017	-10000	0	-10000	0	0
GNGT2	0.022	0.049	-10000	0	-0.47	4	4
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	-0.008	0.023	0.21	2	-10000	0	2

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.002	0.14	-10000	0	-0.38	44	44
HDAC1	0.027	0.011	-10000	0	-10000	0	0
AES	0.027	0.007	-10000	0	-10000	0	0
FBXW11	0.026	0.007	-10000	0	-10000	0	0
DTX1	0.014	0.091	0.21	6	-0.47	13	19
LRP6/FZD1	0.039	0.022	-10000	0	-0.34	1	1
TLE1	0.024	0.026	-10000	0	-0.47	1	1
AP1	-0.075	0.16	-10000	0	-0.29	115	115
NCSTN	0.024	0.01	-10000	0	-10000	0	0
ADAM10	0.027	0.005	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.017	0.18	-10000	0	-0.64	27	27
NICD/RBPSUH	0.008	0.14	-10000	0	-0.37	44	44
WIF1	-0.085	0.19	0.21	9	-0.47	77	86
NOTCH1	-0.018	0.13	-10000	0	-0.39	41	41
PSENEN	0.027	0.006	-10000	0	-10000	0	0
KREMEN2	0.095	0.091	0.21	151	-10000	0	151
DKK1	-0.033	0.18	0.22	15	-0.47	55	70
beta catenin/beta TrCP1	0.041	0.065	0.27	3	-10000	0	3
APH1B	0.027	0.004	-10000	0	-10000	0	0
APH1A	0.025	0.009	-10000	0	-10000	0	0
AXIN1	-0.011	0.088	-10000	0	-0.35	13	13
CtBP/CBP/TCF1/TLE1/AES	0.017	0.051	0.29	2	-0.29	3	5
PSEN1	0.027	0.005	-10000	0	-10000	0	0
FOS	-0.12	0.23	-10000	0	-0.47	124	124
JUN	0.01	0.09	-10000	0	-0.47	14	14
MAP3K7	0.026	0.007	-10000	0	-10000	0	0
CTNNB1	0.031	0.071	0.31	5	-10000	0	5
MAPK3	0.027	0.006	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.11	0.092	0.29	38	-0.19	4	42
HNF1A	0.029	0.021	0.21	5	-10000	0	5
CTBP1	0.027	0.017	0.33	1	-10000	0	1
MYC	-0.041	0.29	-10000	0	-1.3	19	19
NKD1	0.002	0.12	0.21	5	-0.47	22	27
FZD1	0.027	0.027	0.21	1	-0.47	1	2
NOTCH1 precursor/Deltex homolog 1	0.003	0.15	-10000	0	-0.4	42	42
apoptosis	-0.074	0.16	-10000	0	-0.29	115	115
Delta 1/NOTCHprecursor	0.005	0.14	-10000	0	-0.38	44	44
DLL1	0.024	0.045	0.21	2	-0.47	3	5
PPARD	0.021	0.047	-10000	0	-0.75	1	1
Gamma Secretase	0.062	0.036	-10000	0	-10000	0	0
APC	-0.014	0.1	-10000	0	-0.48	12	12
DVL1	0.009	0.034	-10000	0	-0.26	3	3
CSNK2A1	0.026	0.006	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.004	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.04	0.15	0.28	7	-0.3	55	62
LRP6	0.027	0.005	-10000	0	-10000	0	0
CSNK1A1	0.027	0.006	-10000	0	-10000	0	0
NLK	0.013	0.01	-10000	0	-10000	0	0
CCND1	-0.008	0.2	-10000	0	-1.3	10	10
WNT1	0.018	0.026	0.21	3	-10000	0	3
Axin1/APC/beta catenin	0.024	0.11	0.29	4	-0.41	7	11
DKK2	0.064	0.082	0.21	88	-0.47	1	89
NOTCH1 precursor/DVL1	-0.011	0.13	-10000	0	-0.45	15	15
GSK3B	0.027	0.006	-10000	0	-10000	0	0
FRAT1	0.027	0.005	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.003	0.15	-10000	0	-0.4	42	42
PPP2R5D	0.028	0.065	0.26	20	-0.31	3	23
MAPK1	0.027	0.005	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.003	0.13	-10000	0	-0.26	73	73
RBPJ	0.027	0.005	-10000	0	-10000	0	0
CREBBP	0.027	0.009	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.055	0.18	-10000	0	-0.47	65	65
GNB1/GNG2	0.006	0.13	0.32	1	-0.39	18	19
mol:DAG	-0.011	0.12	0.2	3	-0.38	16	19
PLCG1	-0.011	0.12	0.2	3	-0.39	16	19
YES1	-0.014	0.11	0.27	2	-0.42	15	17
FZD3	0.021	0.036	-10000	0	-0.47	2	2
FZD6	0.023	0.011	-10000	0	-10000	0	0
G protein	0.014	0.14	0.31	8	-0.4	16	24
MAP3K7	-0.068	0.14	0.23	1	-0.33	49	50
mol:Ca2+	-0.01	0.11	0.2	3	-0.37	16	19
mol:IP3	-0.011	0.12	0.2	3	-0.38	16	19
NLK	0.007	0.046	-10000	0	-0.88	1	1
GNB1	0.027	0.003	-10000	0	-10000	0	0
CAMK2A	-0.072	0.15	0.23	1	-0.35	54	55
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.01	0.12	0.35	1	-0.3	48	49
CSNK1A1	0.027	0.006	-10000	0	-10000	0	0
GNAS	-0.018	0.11	0.22	2	-0.42	16	18
GO:0007205	-0.015	0.11	-10000	0	-0.37	16	16
WNT6	0.03	0.096	0.21	36	-0.47	10	46
WNT4	-0.002	0.12	0.21	3	-0.47	25	28
NFAT1/CK1 alpha	-0.029	0.15	0.28	2	-0.39	25	27
GNG2	0.02	0.06	-10000	0	-0.47	6	6
WNT5A	0.022	0.071	0.21	10	-0.47	7	17
WNT11	0.017	0.12	0.22	33	-0.47	20	53
CDC42	-0.008	0.11	0.25	2	-0.4	15	17

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.11	0.47	21	-10000	0	21
PI3K Class IB/PDE3B	0.11	-10000	0	-0.47	21	21
PDE3B	0.11	-10000	0	-0.47	21	21

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.22	0.24	-10000	0	-0.47	198	198
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.027	0.011	0.21	1	-10000	0	1
TCEB1	0.024	0.009	-10000	0	-10000	0	0
HIF1A/p53	0.02	0.057	-10000	0	-0.26	13	13
HIF1A	0.009	0.048	-10000	0	-0.26	10	10
COPS5	0.025	0.009	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.059	0.038	-10000	0	-10000	0	0
FIH (dimer)	0.027	0.005	-10000	0	-10000	0	0
CDKN2A	0.11	0.1	0.22	190	-10000	0	190
ARNT/IPAS	-0.13	0.18	-10000	0	-0.34	177	177
HIF1AN	0.027	0.005	-10000	0	-10000	0	0
GNB2L1	0.026	0.006	-10000	0	-10000	0	0
HIF1A/ARNT	0.018	0.05	-10000	0	-0.27	8	8
CUL2	0.026	0.006	-10000	0	-10000	0	0
OS9	0.027	0.005	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.045	0.024	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.021	0.057	-10000	0	-0.26	13	13
PHD1-3/OS9	0.056	0.051	-10000	0	-0.26	8	8
HIF1A/RACK1/Elongin B/Elongin C	0.036	0.061	-10000	0	-0.25	12	12
VHL	0.025	0.009	-10000	0	-10000	0	0
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
HIF1A/JAB1	0.019	0.057	-10000	0	-0.27	12	12
EGLN3	0.017	0.069	-10000	0	-0.47	8	8
EGLN2	0.027	0.005	-10000	0	-10000	0	0
EGLN1	0.027	0.004	-10000	0	-10000	0	0
TP53	0.025	0.008	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.034	0.065	-10000	0	-0.48	6	6
ARNT	0.024	0.01	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.027	0.005	-10000	0	-10000	0	0
HIF1A/p19ARF	0.062	0.096	0.26	3	-0.27	12	15

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.028	0.01	0.21	1	-10000	0	1
SPHK1	0.051	0.069	0.21	56	-0.47	1	57
GNAI2	0.026	0.006	-10000	0	-10000	0	0
mol:S1P	0.021	0.023	0.18	3	-0.26	1	4
GNAO1	-0.12	0.23	-10000	0	-0.47	124	124
mol:Sphinganine-1-P	0.019	0.022	-10000	0	-0.34	1	1
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.059	0.038	-10000	0	-0.2	1	1
GNAI3	0.028	0.003	-10000	0	-10000	0	0
G12/G13	0.037	0.012	-10000	0	-10000	0	0
S1PR3	0.021	0.052	0.33	1	-0.47	4	5
S1PR2	0.027	0.005	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0.012	0.024	0.14	1	-0.21	2	3
S1PR5	0.031	0.051	0.23	13	-0.47	2	15
S1PR4	0.025	0.046	0.21	3	-0.47	3	6
GNAI1	0.024	0.043	-10000	0	-0.47	3	3
S1P/S1P5/G12	0.052	0.047	0.26	2	-0.22	4	6
S1P/S1P3/Gq	-0.029	0.14	-10000	0	-0.3	73	73
S1P/S1P4/Gi	-0.087	0.18	-10000	0	-0.33	112	112
GNAQ	0.025	0.009	-10000	0	-10000	0	0
GNAZ	-0.08	0.2	-10000	0	-0.47	87	87
GNA14	-0.03	0.16	-10000	0	-0.47	45	45
GNA15	0.023	0.043	-10000	0	-0.47	3	3
GNA12	0.026	0.007	-10000	0	-10000	0	0
GNA13	0.027	0.005	-10000	0	-10000	0	0
GNA11	0.026	0.025	-10000	0	-0.47	1	1
ABCC1	0.027	0.019	0.27	2	-10000	0	2

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.014	0.044	-10000	0	-10000	0	0
BIRC5	0.16	0.093	0.22	288	-0.47	1	289
NFKBIA	-0.002	0.039	0.23	3	-10000	0	3
CPEB1	-0.21	0.24	-10000	0	-0.47	189	189
AKT1	-0.002	0.039	0.22	3	-10000	0	3
NDEL1	0.025	0.008	-10000	0	-10000	0	0
Aurora A/BRCA1	0.012	0.04	-10000	0	-10000	0	0
NDEL1/TACC3	0.045	0.047	0.23	6	-10000	0	6
GADD45A	0.028	0.002	-10000	0	-10000	0	0
GSK3B	-0.008	0.024	-10000	0	-10000	0	0
PAK1/Aurora A	0.012	0.045	-10000	0	-0.29	1	1
MDM2	0.036	0.054	0.33	13	-10000	0	13
JUB	0	0	-10000	0	-10000	0	0
TPX2	0.06	0.087	0.3	43	-10000	0	43
TP53	0.015	0.056	0.21	12	-0.2	12	24
DLG7	-0.001	0.034	0.15	11	-10000	0	11
AURKAIP1	0.028	0.01	0.21	1	-10000	0	1
ARHGEF7	0.026	0.006	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.048	0.051	0.25	7	-10000	0	7
G2/M transition of mitotic cell cycle	0.012	0.039	-10000	0	-10000	0	0
AURKA	0.009	0.046	0.2	12	-10000	0	12
AURKB	0.062	0.057	0.16	14	-0.26	3	17
CDC25B	0.011	0.029	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.001	0.025	-10000	0	-10000	0	0
mRNA polyadenylation	-0.12	0.13	-10000	0	-0.26	172	172
Aurora A/CPEB	-0.12	0.13	-10000	0	-0.26	172	172
Aurora A/TACC1/TRAP/chTOG	0.042	0.046	-10000	0	-0.25	2	2
BRCA1	0.028	0.01	0.21	1	-10000	0	1
centrosome duplication	0.012	0.045	-10000	0	-0.29	1	1
regulation of centrosome cycle	0.044	0.046	0.22	6	-10000	0	6
spindle assembly	0.041	0.045	-10000	0	-0.25	2	2
TDRD7	0.025	0.008	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.12	0.076	0.26	13	-0.23	1	14
CENPA	0.081	0.061	0.18	27	-0.28	3	30
Aurora A/PP2A	0.014	0.044	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.016	0.042	0.21	5	-10000	0	5
negative regulation of DNA binding	0.014	0.058	0.21	12	-0.21	9	21
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.037	0.012	-10000	0	-10000	0	0
RASA1	0.027	0.006	-10000	0	-10000	0	0
Ajuba/Aurora A	-0.001	0.026	-10000	0	-10000	0	0
mitotic prometaphase	-0.009	0.028	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.009	0.046	0.2	12	-10000	0	12
TACC1	0.021	0.036	-10000	0	-0.47	2	2
TACC3	0.043	0.059	0.24	30	-10000	0	30
Aurora A/Antizyme1	0.044	0.037	-10000	0	-10000	0	0
Aurora A/RasGAP	0.014	0.042	-10000	0	-10000	0	0
OAZ1	0.027	0.005	-10000	0	-10000	0	0
RAN	0.027	0.005	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	-0.008	0.024	-10000	0	-10000	0	0
GIT1	0.026	0.006	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.048	0.026	-10000	0	-0.28	1	1
Importin alpha/Importin beta/TPX2	0.06	0.086	0.3	43	-10000	0	43
PPP2R5D	0.027	0.004	-10000	0	-10000	0	0
Aurora A/TPX2	0.033	0.093	0.27	40	-10000	0	40
PAK1	0.025	0.025	-10000	0	-0.47	1	1
CKAP5	0.026	0.007	-10000	0	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.031	0.028	0.21	2	-10000	0	2
AES	0.03	0.023	0.2	1	-10000	0	1
FBXW11	0.026	0.007	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.039	0.022	-10000	0	-0.33	1	1
SMAD4	0.026	0.007	-10000	0	-10000	0	0
DKK2	0.065	0.082	0.21	88	-0.47	1	89
TLE1	0.027	0.033	-10000	0	-0.47	1	1
MACF1	0.027	0.006	-10000	0	-10000	0	0
CTNNB1	0.053	0.093	0.28	9	-0.4	3	12
WIF1	-0.082	0.19	0.21	9	-0.47	77	86
beta catenin/RanBP3	0.041	0.14	0.4	43	-0.35	3	46
KREMEN2	0.095	0.091	0.21	151	-10000	0	151
DKK1	-0.033	0.18	0.22	15	-0.47	55	70
beta catenin/beta TrCP1	0.065	0.087	0.28	8	-0.36	3	11
FZD1	0.027	0.027	0.21	1	-0.47	1	2
AXIN2	-0.062	0.36	0.58	16	-1.4	24	40
AXIN1	0.027	0.006	-10000	0	-10000	0	0
RAN	0.027	0.005	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.024	0.11	-10000	0	-0.5	13	13
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.019	0.15	-10000	0	-0.54	19	19
Axin1/APC/GSK3	0.041	0.058	0.27	4	-0.26	1	5
Axin1/APC/GSK3/beta catenin/Macf1	0.032	0.067	0.31	2	-0.4	2	4
HNF1A	0.033	0.031	0.2	7	-10000	0	7
CTBP1	0.031	0.029	0.24	3	-10000	0	3
MYC	0.017	0.37	0.57	56	-1.4	18	74
RANBP3	0.027	0.005	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.11	0.092	0.29	38	-0.19	4	42
NKD1	0.002	0.11	0.21	5	-0.47	22	27
TCF4	0.022	0.062	0.18	1	-0.45	6	7
TCF3	0.03	0.025	0.22	1	-10000	0	1
WNT1/LRP6/FZD1/Axin1	0.064	0.028	-10000	0	-0.26	1	1
Ran/GTP	0.02	0.005	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.019	0.16	0.44	36	-0.46	6	42
LEF1	0.034	0.033	0.2	8	-10000	0	8
DVL1	0.037	0.052	0.23	1	-10000	0	1
CSNK2A1	0.027	0.006	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.018	0.15	-10000	0	-0.49	18	18
DKK1/LRP6/Kremen 2	0.041	0.15	0.28	7	-0.3	55	62
LRP6	0.027	0.005	-10000	0	-10000	0	0
CSNK1A1	0.031	0.027	0.2	2	-10000	0	2
NLK	0.023	0.013	-10000	0	-10000	0	0
CCND1	0.034	0.28	0.6	45	-1.5	7	52
WNT1	0.021	0.024	0.21	3	-10000	0	3
GSK3A	0.027	0.005	-10000	0	-10000	0	0
GSK3B	0.027	0.006	-10000	0	-10000	0	0
FRAT1	0.027	0.005	-10000	0	-10000	0	0
PPP2R5D	0.045	0.07	0.28	21	-0.26	1	22
APC	0.018	0.046	0.23	12	-0.24	1	13
WNT1/LRP6/FZD1	0.057	0.082	0.22	64	-10000	0	64
CREBBP	0.029	0.023	0.17	2	-10000	0	2

×

Syndecan-4-mediated signaling events

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
PTK2	0.003	0.13	-10000	0	-0.51	18	18
Syndecan-4/Syndesmos	0.035	0.14	0.36	3	-0.7	7	10
positive regulation of JNK cascade	-0.019	0.18	0.35	3	-0.52	21	24
Syndecan-4/ADAM12	0.044	0.15	0.38	4	-0.7	7	11
CCL5	0.011	0.11	0.21	13	-0.47	18	31
Rac1/GDP	0.02	0.005	-10000	0	-10000	0	0
DNM2	0.027	0.005	-10000	0	-10000	0	0
ITGA5	0.009	0.094	-10000	0	-0.47	15	15
SDCBP	0.025	0.008	-10000	0	-10000	0	0
PLG	0.001	0.034	0.2	5	-10000	0	5
ADAM12	0.045	0.056	0.21	40	-10000	0	40
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.026	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.035	0.027	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	0.042	0.17	0.36	3	-0.66	10	13
Syndecan-4/CXCL12/CXCR4	-0.02	0.19	0.36	3	-0.57	20	23
Syndecan-4/Laminin alpha3	0.025	0.16	0.38	3	-0.69	8	11
MDK	0.037	0.047	0.22	23	-10000	0	23
Syndecan-4/FZD7	0.028	0.15	0.36	3	-0.68	8	11
Syndecan-4/Midkine	0.043	0.15	0.37	4	-0.7	7	11
FZD7	0.006	0.099	-10000	0	-0.47	17	17
Syndecan-4/FGFR1/FGF	-0.066	0.21	-10000	0	-0.49	47	47
THBS1	0.012	0.084	-10000	0	-0.47	12	12
integrin-mediated signaling pathway	0.024	0.16	0.36	3	-0.66	10	13
positive regulation of MAPKKK cascade	-0.019	0.18	0.35	3	-0.52	21	24
Syndecan-4/TACI	0.017	0.15	0.36	2	-0.62	11	13
CXCR4	0.017	0.069	-10000	0	-0.47	8	8
cell adhesion	0.01	0.081	0.2	13	-0.33	14	27
Syndecan-4/Dynamin	0.035	0.14	0.36	3	-0.75	6	9
Syndecan-4/TSP1	0.031	0.15	0.36	3	-0.72	8	11
Syndecan-4/GIPC	0.035	0.14	0.36	3	-0.7	7	10
Syndecan-4/RANTES	0.028	0.16	0.38	3	-0.66	11	14
ITGB1	0.026	0.006	-10000	0	-10000	0	0
LAMA1	0.04	0.12	0.22	66	-0.47	14	80
LAMA3	0.003	0.15	0.22	35	-0.47	32	67
RAC1	0.026	0.006	-10000	0	-10000	0	0
PRKCA	0.018	0.16	0.76	16	-0.43	4	20
Syndecan-4/alpha-Actinin	0.036	0.14	0.36	3	-0.7	7	10
TFPI	0.017	0.069	-10000	0	-0.47	8	8
F2	0.039	0.052	0.22	28	-10000	0	28
alpha5/beta1 Integrin	0.024	0.071	-10000	0	-0.34	15	15
positive regulation of cell adhesion	0.01	0.16	0.34	2	-0.63	11	13
ACTN1	0.027	0.005	-10000	0	-10000	0	0
TNC	-0.001	0.12	0.21	9	-0.47	25	34
Syndecan-4/CXCL12	-0.025	0.19	0.36	3	-0.59	19	22
FGF6	-0.016	0.006	-10000	0	-10000	0	0
RHOA	0.026	0.006	-10000	0	-10000	0	0
CXCL12	-0.11	0.22	-10000	0	-0.47	108	108
TNFRSF13B	-0.013	0.13	0.21	7	-0.47	28	35
FGF2	-0.13	0.23	-10000	0	-0.47	127	127
FGFR1	-0.066	0.19	-10000	0	-0.47	73	73
Syndecan-4/PI-4-5-P2	0.009	0.13	0.36	1	-0.7	7	8
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.019	0.092	0.2	25	-0.45	11	36
cell migration	-0.02	0.016	-10000	0	-10000	0	0
PRKCD	0.021	0.02	-10000	0	-10000	0	0
vasculogenesis	0.031	0.14	0.36	3	-0.68	8	11
SDC4	0.019	0.14	0.39	1	-0.71	8	9
Syndecan-4/Tenascin C	0.024	0.16	0.36	3	-0.7	10	13
Syndecan-4/PI-4-5-P2/PKC alpha	-0.029	0.022	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0.031	0.14	0.36	3	-0.75	6	9
MMP9	0.067	0.1	0.22	102	-0.46	5	107
Rac1/GTP	0.01	0.083	0.2	13	-0.34	14	27
cytoskeleton organization	0.035	0.14	0.36	3	-0.66	7	10
GIPC1	0.027	0.004	-10000	0	-10000	0	0
Syndecan-4/TFPI	0.032	0.15	0.36	3	-0.69	8	11

×

Visual signal transduction: Rods

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
mol:K +	0.027	0.004	-10000	0	-10000	0	0
GNAT1/GTP	0.018	0.014	0.15	4	-10000	0	4
Metarhodopsin II/Arrestin	0.021	0.008	-10000	0	-10000	0	0
PDE6G/GNAT1/GTP	0.036	0.025	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.013	0.029	0.21	4	-10000	0	4
GRK1	-0.012	0.017	0.21	1	-10000	0	1
CNG Channel	0.045	0.11	0.25	2	-0.24	40	42
mol:Na +	0.058	0.099	0.25	5	-0.25	24	29
mol:ADP	-0.012	0.017	0.21	1	-10000	0	1
RGS9-1/Gbeta5/R9AP	-0.028	0.15	0.24	2	-0.29	91	93
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.077	0.11	0.26	21	-0.25	24	45
CNGB1	0.1	0.094	0.21	173	-10000	0	173
RDH5	0.026	0.025	-10000	0	-0.47	1	1
SAG	-0.016	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.033	0.082	0.3	8	-0.26	9	17
Na + (4 Units)	0.041	0.085	0.29	1	-0.24	24	25
RGS9	-0.077	0.2	-10000	0	-0.47	84	84
GNB1/GNGT1	0.046	0.031	0.24	3	-10000	0	3
GNAT1/GDP	-0.015	0.13	-10000	0	-0.25	89	89
GUCY2D	0.035	0.06	0.21	39	-10000	0	39
GNGT1	0.032	0.048	0.23	20	-10000	0	20
GUCY2F	-0.012	0.015	-10000	0	-10000	0	0
GNB5	0.027	0.004	-10000	0	-10000	0	0
mol:GMP (4 units)	0.017	0.055	0.2	2	-0.25	15	17
mol:11-cis-retinal	0.026	0.025	-10000	0	-0.47	1	1
mol:cGMP	0.047	0.044	0.4	1	-0.24	1	2
GNB1	0.027	0.003	-10000	0	-10000	0	0
Rhodopsin	0.032	0.021	-10000	0	-0.34	1	1
SLC24A1	0.027	0.004	-10000	0	-10000	0	0
CNGA1	0.008	0.13	0.21	25	-0.47	25	50
Metarhodopsin II	0.022	0.009	-10000	0	-10000	0	0
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.066	0.055	0.28	2	-0.25	1	3
RGS9BP	0.01	0.091	0.29	3	-0.47	13	16
Metarhodopsin II/Transducin	0.017	0.02	0.16	3	-0.17	1	4
GCAP Family/Ca ++	0.047	0.032	-10000	0	-0.27	1	1
PDE6A/B	0.025	0.074	-10000	0	-0.34	15	15
mol:Pi	-0.028	0.14	0.23	2	-0.29	91	93
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.052	0.031	0.22	3	-10000	0	3
PDE6B	0.008	0.094	0.21	1	-0.47	15	16
PDE6A	0.025	0.025	0.21	5	-10000	0	5
PDE6G	0.034	0.04	0.23	15	-10000	0	15
RHO	-0.007	0.018	-10000	0	-10000	0	0
PDE6	-0.01	0.15	0.27	1	-0.26	96	97
GUCA1A	0.027	0.049	0.22	21	-10000	0	21
GC2/GCAP Family	0.057	0.034	-10000	0	-0.27	1	1
GUCA1C	-0.013	0.016	0.21	1	-10000	0	1
GUCA1B	0.027	0.033	0.33	2	-0.47	1	3

×

Regulation of Androgen receptor activity

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
HDAC1	0.014	0.006	-10000	0	-10000	0	0
SMARCC1	0.01	0.039	-10000	0	-0.73	1	1
REL	0.025	0.047	0.28	2	-0.47	3	5
HDAC7	-0.054	0.13	-10000	0	-0.31	57	57
JUN	0.01	0.09	-10000	0	-0.47	14	14
EP300	0.027	0.006	-10000	0	-10000	0	0
KAT2B	0.025	0.025	-10000	0	-0.47	1	1
KAT5	0.027	0.005	-10000	0	-10000	0	0
MAPK14	0.002	0.041	-10000	0	-0.34	4	4
FOXO1	0.024	0.026	-10000	0	-0.47	1	1
T-DHT/AR	-0.043	0.14	-10000	0	-0.32	57	57
MAP2K6	0.011	0.059	0.21	1	-0.47	5	6
BRM/BAF57	0.032	0.021	-10000	0	-10000	0	0
MAP2K4	0.015	0.022	-10000	0	-10000	0	0
SMARCA2	0.022	0.013	-10000	0	-10000	0	0
PDE9A	-0.13	0.37	-10000	0	-1	55	55
NCOA2	0	0.11	-10000	0	-0.47	20	20
CEBPA	0.03	0.049	0.24	10	-0.47	2	12
EHMT2	0.027	0.005	-10000	0	-10000	0	0
cell proliferation	-0.015	0.17	0.36	19	-0.39	25	44
NR0B1	0.016	0.061	0.21	32	-10000	0	32
EGR1	-0.087	0.21	-10000	0	-0.47	92	92
RXRs/9cRA	-0.032	0.12	0.22	1	-0.26	93	94
AR/RACK1/Src	-0.014	0.1	0.32	3	-0.3	7	10
AR/GR	-0.079	0.14	-10000	0	-0.26	139	139
GNB2L1	0.027	0.006	-10000	0	-10000	0	0
PKN1	0.026	0.025	-10000	0	-0.47	1	1
RCHY1	0.027	0.004	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0.001	-10000	0	-10000	0	0
MAPK8	0.002	0.037	-10000	0	-0.34	3	3
T-DHT/AR/TIF2/CARM1	-0.025	0.12	0.27	1	-0.34	19	20
SRC	-0.006	0.069	0.19	28	-0.24	7	35
NR3C1	0.013	0.081	-10000	0	-0.47	11	11
KLK3	-0.094	0.25	-10000	0	-1.1	18	18
APPBP2	0.016	0.023	-10000	0	-10000	0	0
TRIM24	0.027	0.019	0.2	3	-10000	0	3
T-DHT/AR/TIP60	-0.03	0.092	0.27	1	-0.31	8	9
TMPRSS2	-0.18	0.43	-10000	0	-1	76	76
RXRG	-0.11	0.2	0.33	1	-0.47	95	96
mol:9cRA	0	0.001	-10000	0	-10000	0	0
RXRA	0.025	0.009	-10000	0	-10000	0	0
RXRB	0.027	0.003	-10000	0	-10000	0	0
CARM1	0.027	0.005	-10000	0	-10000	0	0
NR2C2	0.025	0.03	0.33	1	-0.47	1	2
KLK2	-0.011	0.1	0.35	3	-0.38	6	9
AR	-0.085	0.14	-10000	0	-0.28	134	134
SENP1	0.027	0.004	-10000	0	-10000	0	0
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
MDM2	0.036	0.054	0.33	13	-10000	0	13
SRY	0.001	0.006	0.028	16	-10000	0	16
GATA2	0.025	0.07	0.22	13	-0.47	6	19
MYST2	0	0.001	-10000	0	-10000	0	0
HOXB13	-0.038	0.17	0.23	9	-0.47	54	63
T-DHT/AR/RACK1/Src	-0.016	0.1	0.39	3	-0.31	7	10
positive regulation of transcription	0.025	0.07	0.22	13	-0.47	6	19
DNAJA1	0.016	0.022	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.037	0.22	13	-10000	0	13
NCOA1	0.031	0.017	-10000	0	-10000	0	0
SPDEF	-0.015	0.17	0.21	33	-0.47	46	79
T-DHT/AR/TIF2	-0.024	0.1	0.25	2	-0.32	19	21
T-DHT/AR/Hsp90	-0.029	0.092	0.27	1	-0.32	7	8
GSK3B	0.025	0.009	-10000	0	-10000	0	0
NR2C1	0.027	0.004	-10000	0	-10000	0	0
mol:T-DHT	-0.015	0.055	0.22	6	-0.25	8	14
SIRT1	0.027	0.005	-10000	0	-10000	0	0
ZMIZ2	0.028	0.008	-10000	0	-10000	0	0
POU2F1	0.005	0.064	-10000	0	-0.17	22	22
T-DHT/AR/DAX-1	-0.028	0.1	0.31	4	-0.32	8	12
CREBBP	0.026	0.007	-10000	0	-10000	0	0
SMARCE1	0.025	0.011	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.028	0.002	-10000	0	-10000	0	0
HDAC2	0.026	0.007	-10000	0	-10000	0	0
GNB1/GNG2	0.032	0.087	-10000	0	-0.29	26	26
forebrain development	-0.098	0.25	-10000	0	-0.57	73	73
GNAO1	-0.12	0.23	-10000	0	-0.47	124	124
SMO/beta Arrestin2	0.019	0.083	-10000	0	-0.33	21	21
SMO	0.002	0.11	-10000	0	-0.47	21	21
ARRB2	0.026	0.008	-10000	0	-10000	0	0
GLI3/SPOP	0.037	0.087	0.28	2	-0.48	3	5
mol:GTP	0	0	-10000	0	-10000	0	0
GSK3B	0.027	0.006	-10000	0	-10000	0	0
GNAI2	0.027	0.007	-10000	0	-10000	0	0
SIN3/HDAC complex	0.065	0.021	-10000	0	-10000	0	0
GNAI1	0.024	0.043	-10000	0	-0.47	3	3
XPO1	0.028	0.006	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.08	0.24	-10000	0	-0.64	46	46
SAP30	0.026	0.006	-10000	0	-10000	0	0
mol:GDP	0.002	0.11	-10000	0	-0.47	21	21
MIM/GLI2A	0.029	0.017	-10000	0	-10000	0	0
IFT88	0.026	0.006	-10000	0	-10000	0	0
GNAI3	0.028	0.003	-10000	0	-10000	0	0
GLI2	-0.006	0.097	0.22	1	-0.32	14	15
GLI3	0.025	0.087	0.29	2	-0.5	3	5
CSNK1D	0.027	0.006	-10000	0	-10000	0	0
CSNK1E	0.027	0.006	-10000	0	-10000	0	0
SAP18	0.027	0.005	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.026	0.006	-10000	0	-10000	0	0
GNG2	0.02	0.06	-10000	0	-0.47	6	6
Gi family/GTP	-0.11	0.2	-10000	0	-0.35	129	129
SIN3B	0.027	0.003	-10000	0	-10000	0	0
SIN3A	0.027	0.004	-10000	0	-10000	0	0
GLI3/Su(fu)	0.027	0.092	-10000	0	-0.47	7	7
GLI2/Su(fu)	-0.005	0.12	-10000	0	-0.36	28	28
FOXA2	0.022	0.078	-10000	0	-0.75	2	2
neural tube patterning	-0.098	0.25	-10000	0	-0.57	73	73
SPOP	0.027	0.004	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.015	0.074	-10000	0	-0.38	5	5
GNB1	0.027	0.003	-10000	0	-10000	0	0
CSNK1G2	0.027	0.005	-10000	0	-10000	0	0
CSNK1G3	0.027	0.006	-10000	0	-10000	0	0
MTSS1	0.029	0.017	-10000	0	-10000	0	0
embryonic limb morphogenesis	-0.098	0.25	-10000	0	-0.57	73	73
SUFU	0.011	0.058	-10000	0	-0.22	20	20
LGALS3	0.026	0.025	-10000	0	-0.47	1	1
catabolic process	0.023	0.12	0.28	1	-0.45	9	10
GLI3A/CBP	-0.018	0.13	-10000	0	-0.34	54	54
KIF3A	0.027	0.005	-10000	0	-10000	0	0
GLI1	-0.1	0.26	-10000	0	-0.59	73	73
RAB23	0.026	0.025	-10000	0	-0.47	1	1
CSNK1A1	0.027	0.006	-10000	0	-10000	0	0
IFT172	0.027	0.005	-10000	0	-10000	0	0
RBBP7	0.027	0.004	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.015	0.075	-10000	0	-0.36	6	6
GNAZ	-0.08	0.2	-10000	0	-0.47	87	87
RBBP4	0.028	0.002	-10000	0	-10000	0	0
CSNK1G1	0.027	0.004	-10000	0	-10000	0	0
PIAS1	0.027	0.004	-10000	0	-10000	0	0
PRKACA	0.027	0.003	-10000	0	-10000	0	0
GLI2/SPOP	0.003	0.1	-10000	0	-0.32	15	15
STK36	0.028	0.008	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.099	0.19	-10000	0	-0.43	73	73
PTCH1	-0.087	0.23	-10000	0	-0.65	40	40
MIM/GLI1	-0.072	0.24	-10000	0	-0.59	58	58
CREBBP	-0.018	0.13	-10000	0	-0.34	54	54
Su(fu)/SIN3/HDAC complex	0.023	0.057	-10000	0	-0.35	5	5

×

Effects of Botulinum toxin

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
STX1A	0.009	0.014	0.29	1	-10000	0	1
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.021	0.066	0.17	1	-0.33	13	14
STXBP1	0.013	0.077	-10000	0	-0.47	10	10
ACh/CHRNA1	0.038	0.068	0.17	65	-0.14	5	70
RAB3GAP2/RIMS1/UNC13B	0.035	0.061	-10000	0	-0.28	13	13
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	-0.005	0.087	0.21	1	-0.47	13	14
mol:ACh	-0.004	0.041	0.078	23	-0.13	27	50
RAB3GAP2	0.027	0.005	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0.013	0.085	-10000	0	-0.24	24	24
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.038	0.068	0.17	65	-0.14	5	70
UNC13B	0.025	0.009	-10000	0	-10000	0	0
CHRNA1	0.056	0.072	0.21	69	-10000	0	69
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.008	0.1	0.18	8	-0.3	36	44
SNAP25	-0.01	0.069	0.2	2	-0.27	25	27
VAMP2	0.005	0.002	-10000	0	-10000	0	0
SYT1	-0.01	0.14	0.21	8	-0.47	33	41
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.017	0.047	0.22	1	-0.28	9	10
STX1A/SNAP25 fragment 1/VAMP2	0.013	0.085	-10000	0	-0.24	24	24

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.022	0.049	-10000	0	-0.47	4	4
ANTXR2	-0.003	0.12	-10000	0	-0.47	25	25
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.004	0.016	-10000	0	-0.064	26	26
monocyte activation	0.006	0.086	-10000	0	-0.38	18	18
MAP2K2	-0.001	0.096	-10000	0	-0.57	11	11
MAP2K1	-0.005	0.014	-10000	0	-10000	0	0
MAP2K7	-0.005	0.016	0.13	1	-0.094	1	2
MAP2K6	-0.008	0.032	0.13	1	-0.22	6	7
CYAA	-0.019	0.061	-10000	0	-0.25	26	26
MAP2K4	-0.004	0.013	-10000	0	-0.094	1	1
IL1B	-0.015	0.062	0.17	5	-0.21	29	34
Channel	0.014	0.075	-10000	0	-0.26	26	26
NLRP1	-0.008	0.035	0.13	1	-0.23	8	9
CALM1	0.027	0.005	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.001	0.054	-10000	0	-0.38	7	7
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.004	0.016	0.064	26	-10000	0	26
MAPK3	-0.005	0.016	0.13	1	-0.094	1	2
MAPK1	-0.004	0.019	0.13	4	-0.094	1	5
PGR	-0.075	0.11	-10000	0	-0.25	118	118
PA/Cellular Receptors	0.014	0.082	-10000	0	-0.29	26	26
apoptosis	-0.004	0.016	-10000	0	-0.064	26	26
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.014	0.071	-10000	0	-0.25	26	26
macrophage activation	0.003	0.042	0.17	22	-10000	0	22
TNF	0.036	0.042	0.21	21	-10000	0	21
VCAM1	0.006	0.087	-10000	0	-0.38	18	18
platelet activation	0.001	0.054	-10000	0	-0.38	7	7
MAPKKK cascade	-0.001	0.027	0.11	2	-0.081	21	23
IL18	-0.008	0.046	0.11	2	-0.22	14	16
negative regulation of macrophage activation	-0.004	0.016	-10000	0	-0.064	26	26
LEF	-0.004	0.016	-10000	0	-0.065	26	26
CASP1	-0.005	0.033	0.062	1	-0.1	29	30
mol:cAMP	0.001	0.055	-10000	0	-0.39	7	7
necrosis	-0.004	0.016	-10000	0	-0.064	26	26
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.015	0.071	-10000	0	-0.25	26	26
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.015	0.015	0.3	1	-10000	0	1
MAP4K4	0.013	0.075	0.21	5	-0.3	6	11
BAG4	0.023	0.01	-10000	0	-10000	0	0
PKC zeta/ceramide	0.004	0.054	-10000	0	-0.19	27	27
NFKBIA	0.027	0.005	-10000	0	-10000	0	0
BIRC3	0.005	0.11	0.33	3	-0.47	19	22
BAX	0.005	0.041	-10000	0	-0.4	3	3
RIPK1	0.026	0.007	-10000	0	-10000	0	0
AKT1	0.001	0.058	0.66	3	-10000	0	3
BAD	-0.01	0.047	0.18	3	-0.18	23	26
SMPD1	0.012	0.067	0.16	13	-0.2	21	34
RB1	-0.011	0.044	0.2	1	-0.19	22	23
FADD/Caspase 8	0.025	0.093	0.28	9	-0.31	7	16
MAP2K4	-0.009	0.045	0.18	4	-0.18	19	23
NSMAF	0.025	0.008	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.018	0.079	0.21	47	-0.18	11	58
EGF	0.034	0.047	0.21	24	-10000	0	24
mol:ceramide	-0.011	0.048	-10000	0	-0.2	24	24
MADD	0.026	0.007	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.013	0.015	0.3	1	-10000	0	1
ASAH1	0.023	0.01	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.01	0.044	0.2	1	-0.18	22	23
cell proliferation	-0.054	0.12	0.33	3	-0.2	145	148
BID	0.007	0.12	-10000	0	-0.55	12	12
MAP3K1	-0.011	0.046	0.19	1	-0.18	24	25
EIF2A	0	0.063	0.19	24	-0.19	3	27
TRADD	0.027	0.006	-10000	0	-10000	0	0
CRADD	0.027	0.004	-10000	0	-10000	0	0
MAPK3	0.02	0.074	0.2	40	-0.19	2	42
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.019	0.074	0.2	39	-0.19	2	41
Cathepsin D/ceramide	0.008	0.049	-10000	0	-0.18	24	24
FADD	0.021	0.079	0.27	4	-0.29	5	9
KSR1	-0.004	0.056	0.19	14	-0.19	21	35
MAPK8	-0.004	0.056	-10000	0	-0.22	6	6
PRKRA	-0.011	0.045	0.18	1	-0.18	23	24
PDGFA	0.027	0.016	0.33	1	-10000	0	1
TRAF2	0.025	0.009	-10000	0	-10000	0	0
IGF1	-0.19	0.24	-10000	0	-0.47	176	176
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.011	0.047	-10000	0	-0.2	24	24
CTSD	0.026	0.008	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.039	0.008	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.056	0.13	0.35	3	-0.21	145	148
PRKCD	0.026	0.007	-10000	0	-10000	0	0
PRKCZ	0.024	0.043	-10000	0	-0.47	3	3
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.013	0.015	0.3	1	-10000	0	1
RelA/NF kappa B1	0.039	0.009	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.026	0.025	-10000	0	-0.47	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.015	0.061	-10000	0	-0.32	6	6
TNFR1A/BAG4/TNF-alpha	0.05	0.035	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.015	0.015	0.3	1	-10000	0	1
MAP2K1	0.015	0.075	0.21	35	-0.19	2	37
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
CYCS	0.009	0.044	0.15	13	-0.17	2	15
TNFRSF1A	0.027	0.005	-10000	0	-10000	0	0
NFKB1	0.027	0.004	-10000	0	-10000	0	0
TNFR1A/BAG4	0.033	0.016	-10000	0	-10000	0	0
EIF2AK2	-0.007	0.048	0.18	8	-0.18	18	26
TNF-alpha/TNFR1A/FAN	0.054	0.033	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.021	0.086	-10000	0	-0.4	11	11
MAP2K2	0.016	0.074	0.2	42	-0.19	2	44
SMPD3	0.022	0.054	0.23	3	-0.24	6	9
TNF	0.036	0.042	0.21	21	-10000	0	21
PKC zeta/PAR4	0.036	0.038	-10000	0	-0.34	4	4
mol:PHOSPHOCHOLINE	-0.005	0.038	-10000	0	-0.14	18	18
NF kappa B1/RelA/I kappa B alpha	0.071	0.041	-10000	0	-0.24	4	4
AIFM1	0.007	0.046	0.16	12	-0.16	4	16
BCL2	0.008	0.093	-10000	0	-0.47	15	15

×

ceramide signaling pathway

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
MAP4K4	0.004	0.11	-10000	0	-0.43	12	12
BAG4	0.023	0.01	-10000	0	-10000	0	0
BAD	0.013	0.05	0.16	8	-0.15	8	16
NFKBIA	0.027	0.005	-10000	0	-10000	0	0
BIRC3	0.005	0.11	0.33	3	-0.47	19	22
BAX	0.013	0.051	0.18	5	-0.16	5	10
EnzymeConsortium:3.1.4.12	0.008	0.032	0.081	10	-0.089	12	22
IKBKB	0.02	0.12	0.32	9	-0.41	11	20
MAP2K2	0.034	0.084	0.22	50	-10000	0	50
MAP2K1	0.033	0.084	0.22	49	-10000	0	49
SMPD1	0.006	0.043	0.11	1	-0.14	17	18
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.025	0.12	0.29	10	-0.41	11	21
MAP2K4	0.016	0.048	0.23	5	-0.16	2	7
protein ubiquitination	0.015	0.12	0.39	2	-0.41	12	14
EnzymeConsortium:2.7.1.37	0.036	0.086	0.22	48	-10000	0	48
response to UV	0	0.001	0.002	52	-10000	0	52
RAF1	0.034	0.087	0.22	52	-0.18	2	54
CRADD	0.028	0.004	-10000	0	-10000	0	0
mol:ceramide	0.013	0.05	0.13	8	-0.13	21	29
I-kappa-B-alpha/RELA/p50/ubiquitin	0.035	0.009	-10000	0	-10000	0	0
MADD	0.026	0.007	-10000	0	-10000	0	0
MAP3K1	0.014	0.048	0.15	8	-0.15	6	14
TRADD	0.027	0.006	-10000	0	-10000	0	0
RELA/p50	0.027	0.005	-10000	0	-10000	0	0
MAPK3	0.037	0.083	0.22	47	-10000	0	47
MAPK1	0.036	0.083	0.22	45	-10000	0	45
p50/RELA/I-kappa-B-alpha	0.039	0.01	-10000	0	-10000	0	0
FADD	0.015	0.12	0.3	5	-0.42	11	16
KSR1	0.019	0.063	0.22	17	-0.16	4	21
MAPK8	0.016	0.058	0.22	12	-0.2	3	15
TRAF2	0.025	0.009	-10000	0	-10000	0	0
response to radiation	0	0.001	0.002	16	-10000	0	16
CHUK	0.009	0.11	0.34	2	-0.41	12	14
TNF R/SODD	0.033	0.016	-10000	0	-10000	0	0
TNF	0.037	0.042	0.21	21	-10000	0	21
CYCS	0.02	0.056	0.17	18	-0.15	4	22
IKBKG	0.013	0.12	0.3	4	-0.41	12	16
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.003	0.12	-10000	0	-0.44	13	13
RELA	0.027	0.005	-10000	0	-10000	0	0
RIPK1	0.026	0.007	-10000	0	-10000	0	0
AIFM1	0.018	0.054	0.17	15	-0.15	4	19
TNF/TNF R/SODD	0.05	0.036	-10000	0	-10000	0	0
TNFRSF1A	0.027	0.005	-10000	0	-10000	0	0
response to heat	0	0.001	0.002	16	-10000	0	16
CASP8	0.002	0.14	-10000	0	-0.59	17	17
NSMAF	0.013	0.12	0.27	8	-0.42	12	20
response to hydrogen peroxide	0	0.001	0.002	52	-10000	0	52
BCL2	0.008	0.093	-10000	0	-0.47	15	15

×

TCGA08_p53

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
CDKN2A	0.028	0.039	0.29	6	-10000	0	6
TP53	-0.004	0.052	-10000	0	-0.18	29	29
Senescence	-0.004	0.052	-10000	0	-0.18	29	29
Apoptosis	-0.004	0.052	-10000	0	-0.18	29	29
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.004	0.088	0.32	27	-0.2	5	32
MDM4	0.027	0.004	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.016	0.045	-10000	0	-0.22	13	13
epithelial cell differentiation	0.042	0.056	-10000	0	-0.24	13	13
CYFIP2	0.014	0.077	-10000	0	-0.47	10	10
ENAH	0.019	0.09	0.32	17	-0.29	1	18
EGFR	0.021	0.085	0.33	8	-0.47	9	17
EPHA2	0.021	0.055	-10000	0	-0.47	5	5
MYO6	0.017	0.063	0.27	2	-0.23	13	15
CTNNB1	0.027	0.006	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.042	0.055	-10000	0	-0.28	10	10
AQP5	0.02	0.058	0.37	2	-10000	0	2
CTNND1	0.027	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.018	0.063	0.3	3	-0.23	12	15
regulation of calcium-dependent cell-cell adhesion	0.019	0.073	0.3	5	-0.23	17	22
EGF	0.034	0.047	0.21	24	-10000	0	24
NCKAP1	0.027	0.005	-10000	0	-10000	0	0
AQP3	-0.077	0.19	-10000	0	-0.47	68	68
cortical microtubule organization	0.042	0.056	-10000	0	-0.24	13	13
GO:0000145	0	0.061	0.18	26	-0.22	12	38
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.047	0.058	-10000	0	-0.24	13	13
MLLT4	0.026	0.006	-10000	0	-10000	0	0
ARF6/GDP	-0.017	0.042	-10000	0	-0.28	3	3
ARF6	0.027	0.005	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.059	0.047	0.24	5	-0.26	4	9
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.009	0.055	0.27	2	-0.21	12	14
PVRL2	0.027	0.005	-10000	0	-10000	0	0
ZYX	0.018	0.065	0.36	2	-0.23	13	15
ARF6/GTP	0.064	0.048	-10000	0	-0.24	4	4
CDH1	0.01	0.087	-10000	0	-0.47	13	13
EGFR/EGFR/EGF/EGF	0.031	0.07	-10000	0	-0.24	21	21
RhoA/GDP	0.043	0.055	-10000	0	-0.23	13	13
actin cytoskeleton organization	0.009	0.058	0.26	2	-0.23	12	14
IGF-1R heterotetramer	0.025	0.035	-10000	0	-0.47	2	2
GIT1	0.026	0.006	-10000	0	-10000	0	0
IGF1R	0.025	0.035	-10000	0	-0.47	2	2
IGF1	-0.19	0.24	-10000	0	-0.47	176	176
DIAPH1	0.004	0.15	-10000	0	-0.57	16	16
Wnt receptor signaling pathway	-0.042	0.056	0.24	13	-10000	0	13
RHOA	0.026	0.006	-10000	0	-10000	0	0
RhoA/GTP	-0.017	0.042	-10000	0	-0.4	1	1
CTNNA1	0.027	0.005	-10000	0	-10000	0	0
VCL	0.009	0.059	0.26	2	-0.23	12	14
EFNA1	0.031	0.039	0.3	8	-10000	0	8
LPP	-0.005	0.058	0.27	2	-0.23	1	3
Ephrin A1/EPHA2	0.032	0.059	-10000	0	-0.24	15	15
SEC6/SEC8	0.005	0.037	-10000	0	-0.22	9	9
MGAT3	0.019	0.074	0.32	4	-0.23	17	21
HGF/MET	-0.018	0.12	-10000	0	-0.23	93	93
HGF	-0.076	0.2	0.21	7	-0.47	86	93
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.016	0.046	-10000	0	-0.22	13	13
actin cable formation	0.041	0.096	0.32	22	-0.25	1	23
KIAA1543	-0.002	0.063	0.26	2	-0.24	13	15
KIFC3	0.017	0.063	0.36	2	-0.23	13	15
NCK1	0.026	0.006	-10000	0	-10000	0	0
EXOC3	0.023	0.01	-10000	0	-10000	0	0
ACTN1	0.016	0.062	0.36	1	-0.23	13	14
NCK1/GIT1	0.037	0.012	-10000	0	-10000	0	0
mol:GDP	0.042	0.056	-10000	0	-0.24	13	13
EXOC4	0.027	0.005	-10000	0	-10000	0	0
STX4	0.017	0.062	0.36	2	-0.23	12	14
PIP5K1C	0.018	0.064	0.36	2	-0.23	12	14
LIMA1	0.027	0.004	-10000	0	-10000	0	0
ABI1	0.026	0.006	-10000	0	-10000	0	0
ROCK1	0.023	0.099	0.34	18	-0.34	1	19
adherens junction assembly	0.005	0.077	0.29	4	-0.43	1	5
IGF-1R heterotetramer/IGF1	-0.079	0.14	-10000	0	-0.23	177	177
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.038	0.011	-10000	0	-10000	0	0
MET	0.029	0.022	0.33	2	-10000	0	2
PLEKHA7	0.016	0.066	0.36	1	-0.25	13	14
mol:GTP	0.057	0.046	0.23	5	-0.26	4	9
establishment of epithelial cell apical/basal polarity	0.031	0.1	0.34	18	-10000	0	18
cortical actin cytoskeleton stabilization	0.016	0.045	-10000	0	-0.22	13	13
regulation of cell-cell adhesion	0.009	0.058	0.26	2	-0.23	12	14
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.016	0.046	-10000	0	-0.22	13	13

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.028	0.018	0.27	2	-10000	0	2
EPHB2	0.041	0.047	0.21	28	-10000	0	28
EFNB1	0.009	0.043	-10000	0	-0.34	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.039	0.092	-10000	0	-0.25	28	28
Ephrin B2/EPHB1-2	0.04	0.081	0.27	1	-0.26	23	24
neuron projection morphogenesis	0.023	0.081	-10000	0	-0.24	28	28
Ephrin B1/EPHB1-2/Tiam1	0.035	0.096	0.28	1	-0.26	29	30
DNM1	0.018	0.06	-10000	0	-0.47	6	6
cell-cell signaling	0	0.003	-10000	0	-10000	0	0
MAP2K4	-0.01	0.095	0.24	2	-0.47	15	17
YES1	-0.013	0.14	-10000	0	-0.7	16	16
Ephrin B1/EPHB1-2/NCK2	0.039	0.093	0.28	1	-0.26	28	29
PI3K	0.022	0.1	-10000	0	-0.47	16	16
mol:GDP	0.034	0.095	0.28	1	-0.26	29	30
ITGA2B	0.04	0.052	0.22	31	-10000	0	31
endothelial cell proliferation	0.035	0.011	0.15	1	-10000	0	1
FYN	-0.015	0.15	-10000	0	-0.72	16	16
MAP3K7	-0.014	0.099	-10000	0	-0.51	15	15
FGR	-0.012	0.14	-10000	0	-0.69	17	17
TIAM1	0.023	0.043	-10000	0	-0.47	3	3
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
RGS3	0.025	0.008	-10000	0	-10000	0	0
cell adhesion	-0.006	0.11	-10000	0	-0.43	15	15
LYN	-0.012	0.14	-10000	0	-0.7	16	16
Ephrin B1/EPHB1-2/Src Family Kinases	-0.017	0.13	-10000	0	-0.63	17	17
Ephrin B1/EPHB1-2	-0.014	0.11	-10000	0	-0.55	15	15
SRC	-0.011	0.14	-10000	0	-0.68	17	17
ITGB3	-0.027	0.15	-10000	0	-0.47	44	44
EPHB1	-0.002	0.12	0.21	4	-0.47	25	29
EPHB4	0.027	0.004	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.036	0.011	0.15	1	-10000	0	1
alphaIIb/beta3 Integrin	0.006	0.12	-10000	0	-0.34	44	44
BLK	-0.028	0.15	-10000	0	-0.71	17	17
HCK	-0.017	0.15	-10000	0	-0.69	17	17
regulation of stress fiber formation	-0.037	0.092	0.26	28	-0.28	1	29
MAPK8	-0.008	0.1	0.32	2	-0.49	14	16
Ephrin B1/EPHB1-2/RGS3	0.04	0.092	0.28	1	-0.25	28	29
endothelial cell migration	-0.006	0.092	0.23	7	-0.4	16	23
NCK2	0.027	0.004	-10000	0	-10000	0	0
PTPN13	0.015	0.079	-10000	0	-0.58	7	7
regulation of focal adhesion formation	-0.037	0.092	0.26	28	-0.28	1	29
chemotaxis	-0.038	0.091	0.25	28	-0.28	1	29
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
Rac1/GTP	0.032	0.087	-10000	0	-0.25	28	28
angiogenesis	-0.015	0.11	-10000	0	-0.54	16	16
LCK	-0.012	0.14	-10000	0	-0.68	17	17

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.075	0.14	-10000	0	-0.23	168	168
TC10/GTP	-0.07	0.13	-10000	0	-0.22	167	167
Insulin Receptor/Insulin/IRS1/Shp2	0.052	0.052	-10000	0	-0.26	7	7
HRAS	0.025	0.008	-10000	0	-10000	0	0
APS homodimer	0.029	0.021	0.21	5	-10000	0	5
GRB14	0.051	0.065	0.21	54	-10000	0	54
FOXO3	-0.028	0.18	-10000	0	-0.56	39	39
AKT1	0.004	0.063	0.33	4	-10000	0	4
INSR	0.031	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.054	0.035	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.02	0.055	-10000	0	-0.47	5	5
SORBS1	-0.19	0.24	-10000	0	-0.47	180	180
CRK	0.025	0.008	-10000	0	-10000	0	0
PTPN1	0.01	0.022	-10000	0	-10000	0	0
CAV1	0	0.068	0.21	1	-0.26	22	23
CBL/APS/CAP/Crk-II/C3G	-0.065	0.15	-10000	0	-0.24	174	174
Insulin Receptor/Insulin/IRS1/NCK2	0.053	0.051	-10000	0	-0.26	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.039	0.044	-10000	0	-0.23	7	7
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.028	0.067	-10000	0	-0.34	8	8
RPS6KB1	0.002	0.059	0.32	4	-10000	0	4
PARD6A	0.025	0.025	-10000	0	-0.47	1	1
CBL	0.026	0.007	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.018	0.038	-10000	0	-0.48	2	2
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.027	0.049	-10000	0	-10000	0	0
HRAS/GTP	0.01	0.035	-10000	0	-10000	0	0
Insulin Receptor	0.031	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.058	0.053	-10000	0	-0.24	6	6
PRKCI	0.029	0.049	-10000	0	-0.49	1	1
Insulin Receptor/Insulin/GRB14/PDK1	0.027	0.041	-10000	0	-0.22	7	7
SHC1	0.026	0.017	0.33	1	-10000	0	1
negative regulation of MAPKKK cascade	0.044	0.039	-10000	0	-0.4	2	2
PI3K	0.049	0.049	-10000	0	-0.23	7	7
NCK2	0.027	0.004	-10000	0	-10000	0	0
RHOQ	0.027	0.005	-10000	0	-10000	0	0
mol:H2O2	0.001	0.003	-10000	0	-10000	0	0
HRAS/GDP	0.019	0.006	-10000	0	-10000	0	0
AKT2	0.005	0.063	0.33	4	-10000	0	4
PRKCZ	0.024	0.066	-10000	0	-0.46	4	4
SH2B2	0.029	0.021	0.21	5	-10000	0	5
SHC/SHIP	0.024	0.045	0.21	1	-0.23	9	10
F2RL2	0.013	0.1	0.21	12	-0.47	15	27
TRIP10	0.026	0.025	-10000	0	-0.47	1	1
Insulin Receptor/Insulin/Shc	0.044	0.024	0.22	1	-10000	0	1
TC10/GTP/CIP4/Exocyst	0.035	0.017	-10000	0	-0.26	1	1
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.066	0.036	-10000	0	-10000	0	0
RAPGEF1	0.025	0.009	-10000	0	-10000	0	0
RASA1	0.027	0.006	-10000	0	-10000	0	0
NCK1	0.026	0.006	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	-0.077	0.16	-10000	0	-0.26	175	175
TC10/GDP	0.02	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.054	0.043	-10000	0	-0.27	3	3
INPP5D	0.008	0.048	0.21	1	-0.24	12	13
SOS1	0.027	0.005	-10000	0	-10000	0	0
SGK1	-0.04	0.2	-10000	0	-0.73	30	30
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.027	0.005	-10000	0	-10000	0	0
IRS1	0.017	0.065	-10000	0	-0.47	7	7
p62DOK/RasGAP	0.045	0.04	-10000	0	-0.41	2	2
INS	0.019	0.011	-10000	0	-10000	0	0
mol:PI-3-4-P2	0.008	0.048	0.21	1	-0.24	12	13
GRB2	0.027	0.005	-10000	0	-10000	0	0
EIF4EBP1	0.007	0.066	0.33	5	-10000	0	5
PTPRA	0.028	0.008	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
TC10/GTP/CIP4	0.035	0.017	-10000	0	-0.26	1	1
PDPK1	0.026	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.02	0.042	-10000	0	-0.25	4	4
Insulin Receptor/Insulin/IRS1	0.038	0.046	-10000	0	-0.26	7	7
Insulin Receptor/Insulin/IRS3	0.036	0.018	-10000	0	-10000	0	0
Par3/Par6	0.047	0.064	-10000	0	-0.24	15	15

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0.073	-10000	0	-0.47	9	9
Jak2/Leptin Receptor	0.01	0.16	0.28	10	-0.37	40	50
PTP1B/AKT1	0.025	0.079	-10000	0	-0.3	7	7
FYN	0.022	0.043	-10000	0	-0.47	3	3
p210 bcr-abl/PTP1B	0.016	0.081	0.19	3	-0.3	9	12
EGFR	0.022	0.085	0.32	8	-0.47	9	17
EGF/EGFR	0.034	0.093	0.24	8	-0.31	9	17
CSF1	0.009	0.094	-10000	0	-0.47	15	15
AKT1	0.027	0.005	-10000	0	-10000	0	0
INSR	0.027	0.005	-10000	0	-10000	0	0
PTP1B/N-cadherin	0.036	0.094	0.23	12	-0.29	9	21
Insulin Receptor/Insulin	0.035	0.076	-10000	0	-0.36	3	3
HCK	0.014	0.08	0.21	5	-0.47	10	15
CRK	0.025	0.008	-10000	0	-10000	0	0
TYK2	0.016	0.081	0.25	6	-0.31	7	13
EGF	0.037	0.047	0.22	24	-10000	0	24
YES1	0.025	0.008	-10000	0	-10000	0	0
CAV1	0.02	0.091	0.21	5	-0.3	10	15
TXN	0.027	0.016	0.21	2	-10000	0	2
PTP1B/IRS1/GRB2	0.031	0.087	-10000	0	-0.28	9	9
cell migration	-0.016	0.081	0.3	9	-0.19	3	12
STAT3	0.027	0.004	-10000	0	-10000	0	0
PRLR	0.02	0.12	0.26	28	-0.47	17	45
ITGA2B	0.04	0.052	0.22	31	-10000	0	31
CSF1R	0.004	0.11	0.21	2	-0.47	19	21
Prolactin Receptor/Prolactin	0.027	0.086	0.24	12	-0.34	15	27
FGR	0.025	0.035	-10000	0	-0.47	2	2
PTP1B/p130 Cas	0.026	0.08	0.2	1	-0.31	7	8
Crk/p130 Cas	0.033	0.082	-10000	0	-0.31	6	6
DOK1	0.014	0.093	0.22	1	-0.3	16	17
JAK2	0.002	0.16	0.26	7	-0.37	44	51
Jak2/Leptin Receptor/Leptin	-0.019	0.17	0.3	2	-0.38	50	52
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
PTPN1	0.016	0.082	0.19	3	-0.3	9	12
LYN	0.025	0.008	-10000	0	-10000	0	0
CDH2	0.041	0.073	0.22	40	-0.47	3	43
SRC	0.027	0.078	-10000	0	-0.47	7	7
ITGB3	-0.027	0.15	-10000	0	-0.47	44	44
CAT1/PTP1B	0.007	0.13	0.3	9	-0.35	15	24
CAPN1	0.027	0.005	-10000	0	-10000	0	0
CSK	0.027	0.004	-10000	0	-10000	0	0
PI3K	0.04	0.075	-10000	0	-0.33	3	3
mol:H2O2	0	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.023	0.17	-10000	0	-0.39	48	48
negative regulation of transcription	0.003	0.15	0.26	7	-0.36	44	51
FCGR2A	0.028	0.045	0.23	12	-0.47	1	13
FER	0.025	0.036	-10000	0	-0.47	2	2
alphaIIb/beta3 Integrin	0.006	0.13	-10000	0	-0.34	44	44
BLK	-0.011	0.14	0.21	15	-0.47	30	45
Insulin Receptor/Insulin/Shc	0.042	0.021	0.23	1	-10000	0	1
RHOA	0.027	0.007	-10000	0	-10000	0	0
LEPR	0.008	0.098	-10000	0	-0.46	17	17
BCAR1	0.026	0.006	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.027	0.005	-10000	0	-10000	0	0
mol:NADPH	0.001	0.003	-10000	0	-10000	0	0
TRPV6	-0.018	0.14	0.26	6	-0.37	27	33
PRL	0.008	0.038	0.24	7	-10000	0	7
SOCS3	-0.11	0.4	-10000	0	-1.3	43	43
SPRY2	0.018	0.065	-10000	0	-0.47	7	7
Insulin Receptor/Insulin/IRS1	0.036	0.048	-10000	0	-0.29	7	7
CSF1/CSF1R	0.018	0.12	-10000	0	-0.34	20	20
Ras protein signal transduction	0.008	0.1	0.53	13	-10000	0	13
IRS1	0.017	0.065	-10000	0	-0.47	7	7
INS	0.009	0.014	-10000	0	-10000	0	0
LEP	-0.018	0.14	0.21	15	-0.47	35	50
STAT5B	0.02	0.1	0.22	7	-0.33	14	21
STAT5A	0.02	0.11	0.21	9	-0.32	16	25
GRB2	0.027	0.005	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.023	0.091	-10000	0	-0.29	16	16
CSN2	0.025	0.073	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
LAT	0.038	0.058	-10000	0	-0.42	3	3
YBX1	0.035	0.016	0.32	1	-10000	0	1
LCK	0.024	0.051	0.21	2	-0.47	4	6
SHC1	0.026	0.017	0.33	1	-10000	0	1
NOX4	0.041	0.05	0.22	30	-10000	0	30

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0.073	-10000	0	-0.47	9	9
alphaV beta3 Integrin	-0.003	0.12	-10000	0	-0.34	44	44
PTK2	-0.014	0.13	-10000	0	-0.45	25	25
positive regulation of JNK cascade	-0.012	0.12	-10000	0	-0.33	30	30
CDC42/GDP	-0.003	0.16	-10000	0	-0.41	39	39
Rac1/GDP	-0.004	0.16	-10000	0	-0.41	37	37
RAP1B	0.026	0.008	-10000	0	-10000	0	0
RAP1A	0.028	0.003	-10000	0	-10000	0	0
CTNNB1	0.027	0.006	-10000	0	-10000	0	0
CDC42/GTP	-0.008	0.15	-10000	0	-0.41	30	30
nectin-3/I-afadin	0.013	0.094	-10000	0	-0.33	27	27
RAPGEF1	-0.001	0.15	0.33	2	-0.44	30	32
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.016	0.16	-10000	0	-0.5	31	31
PDGFB-D/PDGFRB	0.016	0.073	-10000	0	-0.47	9	9
TLN1	-0.006	0.048	-10000	0	-0.33	4	4
Rap1/GTP	-0.004	0.1	-10000	0	-0.33	26	26
IQGAP1	0.027	0.004	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.046	0.018	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.013	0.094	-10000	0	-0.33	27	27
PVR	0.027	0.005	-10000	0	-10000	0	0
Necl-5(dimer)	0.027	0.005	-10000	0	-10000	0	0
mol:GDP	-0.021	0.19	-10000	0	-0.5	39	39
MLLT4	0.026	0.006	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
PI3K	0.041	0.093	-10000	0	-0.25	33	33
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.036	0.022	-10000	0	-0.34	1	1
positive regulation of lamellipodium assembly	-0.018	0.13	-10000	0	-0.33	36	36
PVRL1	0.025	0.025	-10000	0	-0.47	1	1
PVRL3	-0.006	0.12	0.21	2	-0.47	27	29
PVRL2	0.027	0.005	-10000	0	-10000	0	0
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
CDH1	0.01	0.087	-10000	0	-0.47	13	13
CLDN1	0.009	0.1	0.23	7	-0.47	17	24
JAM-A/CLDN1	0.023	0.098	-10000	0	-0.26	36	36
SRC	-0.022	0.17	-10000	0	-0.55	32	32
ITGB3	-0.027	0.15	-10000	0	-0.47	44	44
nectin-1(dimer)/I-afadin/I-afadin	0.036	0.022	-10000	0	-0.34	1	1
FARP2	-0.025	0.21	-10000	0	-0.56	34	34
RAC1	0.026	0.006	-10000	0	-10000	0	0
CTNNA1	0.027	0.005	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.028	0.086	-10000	0	-0.28	27	27
nectin-1/I-afadin	0.036	0.022	-10000	0	-0.34	1	1
nectin-2/I-afadin	0.038	0.011	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.035	0.01	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.027	0.087	-10000	0	-0.28	28	28
CDC42/GTP/IQGAP1/filamentous actin	0.036	0.007	-10000	0	-10000	0	0
F11R	0.021	0.027	-10000	0	-0.47	1	1
positive regulation of filopodium formation	-0.012	0.12	-10000	0	-0.33	30	30
alphaV/beta3 Integrin/Talin	0.003	0.11	0.27	3	-0.37	15	18
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.038	0.011	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.038	0.011	-10000	0	-10000	0	0
PIP5K1C	-0.005	0.055	-10000	0	-0.35	5	5
VAV2	-0.034	0.21	-10000	0	-0.54	35	35
RAP1/GDP	0.004	0.14	-10000	0	-0.39	29	29
ITGAV	0.027	0.006	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.028	0.084	-10000	0	-0.28	26	26
nectin-3(dimer)/I-afadin/I-afadin	0.013	0.094	-10000	0	-0.33	27	27
Rac1/GTP	-0.014	0.16	-10000	0	-0.4	36	36
PTPRM	-0.005	0.07	-10000	0	-0.23	31	31
E-cadherin/beta catenin/alpha catenin	0.056	0.065	-10000	0	-0.25	12	12
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.028	0.003	-10000	0	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.033	0.066	-10000	0	-0.28	13	13
cell-cell adhesion	0.011	0.06	0.21	31	-10000	0	31
Ephrin B/EPHB2/RasGAP	0.069	0.068	0.29	1	-0.25	9	10
ITSN1	0.027	0.005	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
SHC1	0.026	0.017	0.33	1	-10000	0	1
Ephrin B1/EPHB3	0.037	0.032	-10000	0	-0.28	2	2
Ephrin B1/EPHB1	0.016	0.078	-10000	0	-0.28	25	25
HRAS/GDP	0.004	0.086	-10000	0	-0.28	14	14
Ephrin B/EPHB1/GRB7	0.042	0.1	0.26	1	-0.25	37	38
Endophilin/SYNJ1	0.012	0.055	0.27	2	-0.23	9	11
KRAS	0.027	0.016	0.33	1	-10000	0	1
Ephrin B/EPHB1/Src	0.04	0.095	0.26	1	-0.25	33	34
endothelial cell migration	0.05	0.028	0.21	1	-0.24	1	2
GRB2	0.027	0.005	-10000	0	-10000	0	0
GRB7	0.028	0.084	0.31	14	-0.47	7	21
PAK1	0.012	0.065	0.35	1	-0.24	11	12
HRAS	0.025	0.008	-10000	0	-10000	0	0
RRAS	0.01	0.057	0.27	2	-0.24	11	13
DNM1	0.017	0.06	-10000	0	-0.47	6	6
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.003	0.084	0.35	1	-0.23	32	33
lamellipodium assembly	-0.011	0.06	-10000	0	-0.21	31	31
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.008	0.078	-10000	0	-0.24	23	23
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
EPHB2	0.04	0.047	0.21	28	-10000	0	28
EPHB3	0.032	0.055	0.23	16	-0.47	2	18
EPHB1	-0.002	0.12	0.21	4	-0.47	25	29
EPHB4	0.027	0.004	-10000	0	-10000	0	0
mol:GDP	-0.004	0.07	-10000	0	-0.28	13	13
Ephrin B/EPHB2	0.057	0.062	0.27	1	-0.25	9	10
Ephrin B/EPHB3	0.05	0.062	0.22	2	-0.25	11	13
JNK cascade	0.009	0.095	0.3	19	-0.25	25	44
Ephrin B/EPHB1	0.031	0.089	0.24	1	-0.24	33	34
RAP1/GDP	0.014	0.089	0.28	5	-0.26	12	17
EFNB2	0.028	0.018	0.27	2	-10000	0	2
EFNB3	0.017	0.082	0.21	8	-0.47	10	18
EFNB1	0.027	0.004	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.039	0.082	0.27	1	-0.26	23	24
RAP1B	0.026	0.008	-10000	0	-10000	0	0
RAP1A	0.028	0.003	-10000	0	-10000	0	0
CDC42/GTP	0.029	0.087	-10000	0	-0.26	15	15
Rap1/GTP	0.007	0.065	-10000	0	-0.22	23	23
axon guidance	0.033	0.065	-10000	0	-0.28	13	13
MAPK3	0.003	0.075	0.24	6	-0.3	5	11
MAPK1	0.003	0.074	-10000	0	-0.3	5	5
Rac1/GDP	0.004	0.088	0.25	6	-0.27	14	20
actin cytoskeleton reorganization	-0.008	0.058	-10000	0	-0.22	12	12
CDC42/GDP	0.005	0.09	0.28	6	-0.27	14	20
PI3K	0.055	0.03	0.22	1	-0.24	1	2
EFNA5	0.011	0.088	0.21	1	-0.47	13	14
Ephrin B2/EPHB4	0.036	0.011	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.025	0.044	-10000	0	-0.22	9	9
CDC42	0.028	0.003	-10000	0	-10000	0	0
RAS family/GTP	0.003	0.063	-10000	0	-0.21	22	22
PTK2	0.052	0.17	0.57	38	-10000	0	38
MAP4K4	0.009	0.095	0.3	19	-0.25	25	44
SRC	0.026	0.007	-10000	0	-10000	0	0
KALRN	0.026	0.04	0.21	4	-0.47	2	6
Intersectin/N-WASP	0.039	0.009	-10000	0	-10000	0	0
neuron projection morphogenesis	0.016	0.092	0.29	15	-0.29	3	18
MAP2K1	0.003	0.074	-10000	0	-0.3	6	6
WASL	0.027	0.004	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.054	0.088	-10000	0	-0.26	25	25
cell migration	0.016	0.1	0.26	6	-0.35	6	12
NRAS	0.028	0.002	-10000	0	-10000	0	0
SYNJ1	0.012	0.055	0.27	2	-0.24	9	11
PXN	0.027	0.004	-10000	0	-10000	0	0
TF	-0.009	0.067	0.19	19	-0.23	17	36
HRAS/GTP	0.027	0.08	-10000	0	-0.22	30	30
Ephrin B1/EPHB1-2	0.039	0.083	-10000	0	-0.26	25	25
cell adhesion mediated by integrin	0.002	0.052	0.24	9	-0.19	12	21
RAC1	0.026	0.006	-10000	0	-10000	0	0
mol:GTP	0.032	0.086	-10000	0	-0.23	33	33
RAC1-CDC42/GTP	-0.007	0.064	-10000	0	-0.22	25	25
RASA1	0.027	0.006	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.014	0.089	0.26	4	-0.26	13	17
ruffle organization	-0.005	0.088	0.37	3	-0.26	2	5
NCK1	0.026	0.006	-10000	0	-10000	0	0
receptor internalization	-0.008	0.061	0.18	16	-0.24	14	30
Ephrin B/EPHB2/KALRN	0.068	0.072	0.29	1	-0.25	11	12
ROCK1	0.023	0.047	0.19	24	-0.26	2	26
RAS family/GDP	-0.013	0.054	-10000	0	-0.23	12	12
Rac1/GTP	0.001	0.066	-10000	0	-0.22	31	31
Ephrin B/EPHB1/Src/Paxillin	0.006	0.075	-10000	0	-0.24	32	32

×

Caspase cascade in apoptosis

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
TOP1	-0.008	0.12	-10000	0	-0.44	19	19
ACTA1	-0.028	0.14	-10000	0	-0.47	25	25
NUMA1	-0.01	0.12	-10000	0	-0.45	22	22
SPTAN1	-0.029	0.14	0.35	1	-0.48	24	25
LIMK1	-0.028	0.14	-10000	0	-0.48	23	23
BIRC3	0.005	0.11	0.33	3	-0.47	19	22
BIRC2	0.028	0.022	0.33	2	-10000	0	2
BAX	0.027	0.004	-10000	0	-10000	0	0
CASP10	-0.033	0.096	-10000	0	-0.37	27	27
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.028	0.015	0.33	1	-10000	0	1
PTK2	-0.009	0.12	-10000	0	-0.48	19	19
DIABLO	0.027	0.004	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.028	0.13	0.35	1	-0.46	24	25
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.027	0.004	-10000	0	-10000	0	0
GSN	-0.032	0.14	-10000	0	-0.48	25	25
MADD	0.026	0.007	-10000	0	-10000	0	0
TFAP2A	0.033	0.1	-10000	0	-0.63	7	7
BID	-0.008	0.062	0.18	1	-0.23	27	28
MAP3K1	-0.018	0.1	-10000	0	-0.39	21	21
TRADD	0.027	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.04	0.007	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.027	0.14	0.34	1	-0.48	24	25
CASP9	0.028	0.003	-10000	0	-10000	0	0
DNA repair	-0.002	0.052	0.22	2	-0.16	7	9
neuron apoptosis	0.009	0.096	-10000	0	-0.68	6	6
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.02	0.14	-10000	0	-0.43	31	31
APAF1	0.027	0.004	-10000	0	-10000	0	0
CASP6	-0.002	0.14	-10000	0	-0.91	7	7
TRAF2	0.025	0.009	-10000	0	-10000	0	0
ICAD/CAD	-0.03	0.13	-10000	0	-0.47	23	23
CASP7	-0.001	0.093	0.28	17	-0.34	4	21
KRT18	0.018	0.057	-10000	0	-0.49	3	3
apoptosis	-0.016	0.14	0.27	2	-0.51	21	23
DFFA	-0.03	0.14	-10000	0	-0.49	23	23
DFFB	-0.03	0.14	-10000	0	-0.49	23	23
PARP1	0.002	0.052	0.17	7	-0.22	2	9
actin filament polymerization	0.027	0.12	0.46	22	-10000	0	22
TNF	0.036	0.042	0.21	21	-10000	0	21
CYCS	-0.002	0.053	0.18	1	-0.2	16	17
SATB1	0	0.14	-10000	0	-0.85	7	7
SLK	-0.029	0.14	-10000	0	-0.48	24	24
p15 BID/BAX	0.004	0.07	-10000	0	-0.26	15	15
CASP2	0.008	0.071	0.21	5	-0.28	8	13
JNK cascade	0.018	0.1	0.39	21	-10000	0	21
CASP3	-0.03	0.14	-10000	0	-0.48	26	26
LMNB2	0.013	0.11	-10000	0	-0.38	15	15
RIPK1	0.026	0.007	-10000	0	-10000	0	0
CASP4	0.027	0.016	0.33	1	-10000	0	1
Mammalian IAPs/DIABLO	0.05	0.072	0.24	1	-0.26	18	19
negative regulation of DNA binding	0.033	0.1	-10000	0	-0.62	7	7
stress fiber formation	-0.029	0.13	-10000	0	-0.47	24	24
GZMB	-0.017	0.12	-10000	0	-0.42	29	29
CASP1	0.008	0.047	-10000	0	-0.3	9	9
LMNB1	0.012	0.12	-10000	0	-0.43	16	16
APP	0.009	0.098	-10000	0	-0.69	6	6
TNFRSF1A	0.027	0.005	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.008	0.002	-10000	0	-10000	0	0
VIM	-0.014	0.14	0.28	2	-0.5	21	23
LMNA	0.02	0.079	-10000	0	-0.32	8	8
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.008	0.072	-10000	0	-0.28	10	10
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.027	0.14	0.29	1	-0.48	23	24
APAF-1/Caspase 9	0.016	0.063	-10000	0	-0.54	3	3
nuclear fragmentation during apoptosis	-0.01	0.12	-10000	0	-0.44	22	22
CFL2	-0.028	0.13	-10000	0	-0.47	22	22
GAS2	-0.049	0.15	-10000	0	-0.47	27	27
positive regulation of apoptosis	0.018	0.1	-10000	0	-0.4	12	12
PRF1	0.012	0.1	0.21	11	-0.47	16	27

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	0.036	0.069	-10000	0	-0.37	3	3
epithelial cell differentiation	0.012	0.087	-10000	0	-0.41	3	3
ITCH	0.028	0.02	0.31	1	-10000	0	1
WWP1	0.033	0.057	-10000	0	-10000	0	0
FYN	0.022	0.043	-10000	0	-0.47	3	3
EGFR	0.021	0.085	0.33	8	-0.47	9	17
PRL	0.001	0.038	0.24	7	-10000	0	7
neuron projection morphogenesis	0.019	0.1	0.31	9	-0.35	1	10
PTPRZ1	-0.071	0.22	0.21	41	-0.47	89	130
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.02	0.1	-10000	0	-0.38	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.008	0.097	0.3	1	-0.32	6	7
ADAM17	0.029	0.019	0.31	1	-10000	0	1
ErbB4/ErbB4	0.03	0.041	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.043	0.055	-10000	0	-10000	0	0
NCOR1	0.025	0.009	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.002	0.1	0.27	1	-0.37	3	4
GRIN2B	-0.008	0.099	0.27	3	-0.35	4	7
ErbB4/ErbB2/betacellulin	0.019	0.094	0.28	3	-0.31	2	5
STAT1	0.029	0.019	0.21	4	-10000	0	4
HBEGF	0.012	0.084	-10000	0	-0.47	12	12
PRLR	0.019	0.12	0.26	28	-0.47	17	45
E4ICDs/ETO2	0.036	0.066	-10000	0	-10000	0	0
axon guidance	0.025	0.097	0.33	2	-10000	0	2
NEDD4	0.026	0.027	-10000	0	-0.45	1	1
Prolactin receptor/Prolactin receptor/Prolactin	0.024	0.084	0.24	10	-0.34	15	25
CBFA2T3	0.012	0.084	-10000	0	-0.47	12	12
ErbB4/ErbB2/HBEGF	0.041	0.064	0.29	2	-0.42	1	3
MAPK3	0.014	0.1	0.3	4	-0.36	1	5
STAT1 (dimer)	0.047	0.049	-10000	0	-10000	0	0
MAPK1	0.017	0.1	0.3	5	-0.36	1	6
JAK2	0.024	0.01	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.004	0.095	0.28	4	-0.36	2	6
NRG1	-0.031	0.12	0.31	3	-0.34	53	56
NRG3	0.011	0.043	0.21	13	-10000	0	13
NRG2	-0.18	0.24	-10000	0	-0.47	164	164
NRG4	-0.019	0.14	-10000	0	-0.47	37	37
heart development	0.025	0.097	0.33	2	-10000	0	2
neural crest cell migration	-0.004	0.094	0.27	4	-0.35	2	6
ERBB2	0.025	0.054	0.3	14	-10000	0	14
WWOX/E4ICDs	0.039	0.048	-10000	0	-10000	0	0
SHC1	0.026	0.017	0.33	1	-10000	0	1
ErbB4/EGFR/neuregulin 4	0.028	0.1	-10000	0	-0.38	6	6
apoptosis	-0.026	0.075	0.41	3	-10000	0	3
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.07	0.15	-10000	0	-0.34	15	15
ErbB4/ErbB2/epiregulin	0.033	0.11	0.3	7	-0.39	1	8
ErbB4/ErbB4/betacellulin/betacellulin	0.01	0.1	-10000	0	-0.35	3	3
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.042	0.094	-10000	0	-0.36	2	2
MDM2	0.043	0.077	0.32	10	-10000	0	10
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.003	0.092	-10000	0	-0.31	2	2
STAT5A	0.027	0.1	0.34	4	-0.42	1	5
ErbB4/EGFR/neuregulin 1 beta	-0.001	0.11	0.28	2	-0.37	3	5
DLG4	0.025	0.008	-10000	0	-10000	0	0
GRB2/SHC	0.037	0.016	0.24	1	-10000	0	1
E4ICDs/TAB2/NCoR1	0.034	0.043	-10000	0	-10000	0	0
STAT5A (dimer)	0.028	0.11	-10000	0	-0.47	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.042	0.1	0.37	1	-10000	0	1
LRIG1	-0.014	0.14	-10000	0	-0.47	33	33
EREG	-0.017	0.19	0.21	53	-0.47	55	108
BTC	-0.035	0.16	-10000	0	-0.47	49	49
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.021	0.094	0.35	1	-10000	0	1
ERBB4	0.021	0.026	-10000	0	-10000	0	0
STAT5B	0.027	0.004	-10000	0	-10000	0	0
YAP1	0.013	0.081	0.34	1	-0.47	9	10
GRB2	0.027	0.005	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.027	0.08	0.27	1	-0.32	3	4
glial cell differentiation	-0.034	0.043	-10000	0	-10000	0	0
WWOX	0.023	0.026	-10000	0	-0.47	1	1
cell proliferation	-0.031	0.15	0.34	5	-0.48	15	20

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.042	0.087	-10000	0	-0.59	2	2
UGCG	-0.063	0.23	-10000	0	-0.59	59	59
AKT1/mTOR/p70S6K/Hsp90/TERT	0.072	0.12	0.27	8	-0.31	9	17
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.059	0.22	-10000	0	-0.58	59	59
mol:DAG	0.009	0.11	-10000	0	-0.77	7	7
CaM/Ca2+/Calcineurin A alpha-beta B1	0.044	0.15	0.32	1	-0.44	24	25
FRAP1	0.036	0.16	0.34	1	-0.49	26	27
FOXO3	0.039	0.14	0.31	2	-0.42	24	26
AKT1	0.039	0.15	0.34	1	-0.44	26	27
GAB2	0.025	0.026	-10000	0	-0.47	1	1
SMPD1	-0.014	0.16	-10000	0	-0.57	28	28
SGMS1	0.016	0.082	-10000	0	-0.56	7	7
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	0.017	-10000	0	-0.28	1	1
CALM1	0.027	0.005	-10000	0	-10000	0	0
cell proliferation	-0.001	0.18	0.28	3	-0.46	33	36
EIF3A	0.027	0.006	-10000	0	-10000	0	0
PI3K	0.038	0.025	-10000	0	-0.33	1	1
RPS6KB1	0.033	0.023	-10000	0	-10000	0	0
mol:sphingomyelin	0.009	0.11	-10000	0	-0.77	7	7
natural killer cell activation	0	0.003	-10000	0	-0.013	9	9
JAK3	0.03	0.014	0.22	2	-10000	0	2
PIK3R1	0.026	0.026	-10000	0	-0.46	1	1
JAK1	0.029	0.005	-10000	0	-10000	0	0
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MYC	0.039	0.24	0.39	6	-0.92	20	26
MYB	0.063	0.086	0.43	1	-1.1	1	2
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.038	0.12	0.25	1	-0.47	10	11
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.054	0.032	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.04	0.12	0.24	1	-0.46	10	11
Rac1/GDP	0.02	0.021	-10000	0	-0.25	1	1
T cell proliferation	0.038	0.11	0.3	2	-0.44	9	11
SHC1	0.026	0.017	0.33	1	-10000	0	1
RAC1	0.026	0.006	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.007	0.008	0.027	36	-0.076	1	37
PRKCZ	0.037	0.11	0.36	1	-0.46	9	10
NF kappa B1 p50/RelA	0.056	0.15	0.33	1	-0.44	22	23
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.024	0.073	-10000	0	-0.43	7	7
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
IL2RA	0.012	0.11	0.21	19	-0.47	17	36
IL2RB	0.023	0.058	0.27	2	-0.47	5	7
TERT	0.12	0.11	0.24	174	-10000	0	174
E2F1	0.066	0.059	0.28	1	-0.31	1	2
SOS1	0.027	0.007	-10000	0	-10000	0	0
RPS6	0.024	0.01	-10000	0	-10000	0	0
mol:cAMP	-0.003	0.004	0.032	1	-0.015	15	16
PTPN11	0.026	0.01	-10000	0	-10000	0	0
IL2RG	0.022	0.079	0.22	9	-0.47	9	18
actin cytoskeleton organization	0.038	0.11	0.3	2	-0.44	9	11
GRB2	0.027	0.008	-10000	0	-10000	0	0
IL2	0.019	0.013	-10000	0	-10000	0	0
PIK3CA	0.027	0.009	-10000	0	-10000	0	0
Rac1/GTP	0.044	0.032	-10000	0	-0.24	1	1
LCK	0.025	0.051	0.22	2	-0.47	4	6
BCL2	0.02	0.21	-10000	0	-0.75	22	22

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.034	0.011	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.026	0.007	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.021	0.056	0.21	1	-0.47	5	6
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.025	0.009	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.017	0.015	-10000	0	-0.19	1	1
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.025	0.008	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.026	0.006	-10000	0	-10000	0	0
FYN	0.022	0.043	-10000	0	-0.47	3	3
MAP3K12	0.026	0.025	-10000	0	-0.47	1	1
FGR	0.025	0.035	-10000	0	-0.47	2	2
p38 alpha/TAB1	-0.037	0.081	-10000	0	-0.29	29	29
PRKG1	-0.082	0.2	-10000	0	-0.47	87	87
DUSP8	0.001	0.11	-10000	0	-0.47	20	20
PGK/cGMP/p38 alpha	-0.038	0.14	-10000	0	-0.32	54	54
apoptosis	-0.036	0.078	-10000	0	-0.28	29	29
RAL/GTP	0.036	0.009	-10000	0	-10000	0	0
LYN	0.025	0.008	-10000	0	-10000	0	0
DUSP1	-0.1	0.22	-10000	0	-0.47	105	105
PAK1	0.025	0.025	-10000	0	-0.47	1	1
SRC	0.026	0.007	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.06	0.027	-10000	0	-10000	0	0
TRAF6	0.026	0.008	-10000	0	-10000	0	0
RAC1	0.026	0.006	-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	0.027	0.01	0.21	1	-10000	0	1
RAC1-CDC42/GTP	0.035	0.009	-10000	0	-10000	0	0
MAPK11	0.011	0.12	0.27	8	-0.32	19	27
BLK	-0.011	0.14	0.21	15	-0.47	30	45
HCK	0.014	0.08	0.21	5	-0.47	10	15
MAP2K3	0.025	0.008	-10000	0	-10000	0	0
DUSP16	0.027	0.005	-10000	0	-10000	0	0
DUSP10	0.03	0.021	0.21	5	-10000	0	5
TRAF6/MEKK3	0.031	0.012	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0.12	0.23	10	-0.32	27	37
positive regulation of innate immune response	0.01	0.14	0.29	8	-0.36	23	31
LCK	0.024	0.051	0.21	2	-0.47	4	6
p38alpha-beta/MKP7	0.02	0.14	0.32	6	-0.35	21	27
p38alpha-beta/MKP5	0.02	0.14	0.3	6	-0.35	21	27
PGK/cGMP	-0.057	0.14	-10000	0	-0.33	87	87
PAK2	0.026	0.007	-10000	0	-10000	0	0
p38alpha-beta/MKP1	-0.029	0.16	0.27	3	-0.37	51	54
CDC42	0.028	0.003	-10000	0	-10000	0	0
RALB	0.027	0.004	-10000	0	-10000	0	0
RALA	0.028	0.016	0.33	1	-10000	0	1
PAK3	0.014	0.041	0.21	12	-10000	0	12

×

IL27-mediated signaling events

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
TGFB1	0.029	0.006	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.014	0.12	0.41	7	-0.48	1	8
IL27/IL27R/JAK1	0.039	0.15	0.9	1	-10000	0	1
TBX21	-0.013	0.16	0.5	3	-0.46	21	24
IL12B	0.027	0.039	0.22	14	-10000	0	14
IL12A	0.009	0.015	0.29	1	-10000	0	1
IL6ST	-0.04	0.17	-10000	0	-0.47	55	55
IL27RA/JAK1	0.024	0.036	-10000	0	-10000	0	0
IL27	0.034	0.05	0.22	23	-10000	0	23
TYK2	0.03	0.007	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.098	0.15	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.014	0.12	0.41	7	-0.48	1	8
T cell proliferation during immune response	0.014	0.12	0.41	7	-0.48	1	8
MAPKKK cascade	-0.014	0.12	0.48	1	-0.41	7	8
STAT3	0.027	0.004	-10000	0	-10000	0	0
STAT2	0.027	0.004	-10000	0	-10000	0	0
STAT1	0.029	0.02	0.22	4	-10000	0	4
IL12RB1	0.025	0.088	0.21	20	-0.47	10	30
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.002	0.15	0.48	4	-0.48	11	15
IL27/IL27R/JAK2/TYK2	-0.014	0.12	0.48	1	-0.42	7	8
positive regulation of T cell mediated cytotoxicity	-0.014	0.12	0.48	1	-0.41	7	8
STAT1 (dimer)	0.042	0.21	0.6	22	-0.55	9	31
JAK2	0.026	0.011	-10000	0	-10000	0	0
JAK1	0.028	0.006	-10000	0	-10000	0	0
STAT2 (dimer)	-0.001	0.12	0.43	1	-0.4	7	8
T cell proliferation	-0.1	0.17	0.44	1	-0.42	60	61
IL12/IL12R/TYK2/JAK2	0.005	0.2	-10000	0	-0.76	22	22
IL17A	-0.098	0.15	-10000	0	-10000	0	0
mast cell activation	0.014	0.12	0.41	7	-0.48	1	8
IFNG	0.007	0.032	0.17	1	-0.098	4	5
T cell differentiation	-0.001	0.005	0.011	2	-0.016	8	10
STAT3 (dimer)	-0.002	0.12	0.43	1	-0.4	7	8
STAT5A (dimer)	-0.002	0.12	0.43	1	-0.4	7	8
STAT4 (dimer)	-0.013	0.13	0.43	1	-0.4	16	17
STAT4	0.002	0.11	-10000	0	-0.47	20	20
T cell activation	-0.008	0.005	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	0.012	0.11	-10000	0	-10000	0	0
GATA3	-0.015	0.39	0.6	45	-1.3	26	71
IL18	0.003	0.041	-10000	0	-0.33	6	6
positive regulation of mast cell cytokine production	-0.001	0.12	0.43	1	-0.39	7	8
IL27/EBI3	0.047	0.056	0.25	7	-0.34	3	10
IL27RA	0.008	0.028	-10000	0	-10000	0	0
IL6	-0.18	0.24	-10000	0	-0.46	170	170
STAT5A	0.026	0.025	-10000	0	-0.47	1	1
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.013	0.03	-10000	0	-10000	0	0
IL1B	-0.004	0.074	0.29	2	-0.33	18	20
EBI3	0.029	0.05	0.22	7	-0.46	3	10
TNF	0.01	0.009	-10000	0	-10000	0	0

×

IL2 signaling events mediated by STAT5

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
GAB2	0.026	0.025	-10000	0	-0.47	1	1
ELF1	0.02	0.078	-10000	0	-0.35	16	16
CCNA2	0.076	0.083	0.22	105	-10000	0	105
PIK3CA	0.027	0.007	-10000	0	-10000	0	0
JAK3	0.029	0.013	0.21	2	-10000	0	2
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
JAK1	0.028	0.003	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.047	0.098	0.27	1	-0.48	6	7
SHC1	0.027	0.017	0.33	1	-10000	0	1
SP1	0.005	0.098	-10000	0	-0.34	31	31
IL2RA	-0.007	0.15	-10000	0	-0.7	17	17
IL2RB	0.022	0.058	0.27	2	-0.47	5	7
SOS1	0.028	0.005	-10000	0	-10000	0	0
IL2RG	0.021	0.079	0.21	9	-0.47	9	18
G1/S transition of mitotic cell cycle	-0.02	0.22	0.36	3	-0.68	36	39
PTPN11	0.027	0.005	-10000	0	-10000	0	0
CCND2	-0.037	0.2	-10000	0	-0.73	31	31
LCK	0.024	0.051	0.21	2	-0.47	4	6
GRB2	0.027	0.005	-10000	0	-10000	0	0
IL2	0.017	0.011	-10000	0	-10000	0	0
CDK6	0.015	0.077	-10000	0	-0.47	10	10
CCND3	0.054	0.095	0.35	1	-0.53	3	4

×

EGFR-dependent Endothelin signaling events

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
HRAS	0.025	0.008	-10000	0	-10000	0	0
EGFR	0.021	0.085	0.33	8	-0.47	9	17
EGF/EGFR	0.013	0.11	-10000	0	-0.24	55	55
EGF/EGFR dimer/SHC/GRB2/SOS1	0.074	0.057	0.35	1	-0.24	3	4
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	-0.037	0.16	-10000	0	-0.47	52	52
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	0.034	0.047	0.21	24	-10000	0	24
EGF/EGFR dimer/SHC	0.052	0.063	0.25	8	-0.28	7	15
mol:GDP	0.066	0.054	0.32	1	-0.24	3	4
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0.026	0.052	0.28	5	-0.47	3	8
GRB2/SOS1	0.039	0.01	-10000	0	-10000	0	0
HRAS/GTP	0.04	0.039	0.22	1	-0.23	3	4
SHC1	0.026	0.017	0.33	1	-10000	0	1
HRAS/GDP	0.058	0.052	0.28	1	-0.23	3	4
FRAP1	-0.006	0.035	0.15	12	-0.23	3	15
EGF/EGFR dimer	0.04	0.071	0.24	7	-0.34	9	16
SOS1	0.027	0.005	-10000	0	-10000	0	0
GRB2	0.027	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-1	-0.009	0.13	0.24	3	-0.34	51	54

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.034	0.12	0.29	7	-0.41	16	23
PDGFB-D/PDGFRB/SLAP	0.016	0.095	-10000	0	-0.4	18	18
PDGFB-D/PDGFRB/APS/CBL	0.045	0.055	-10000	0	-0.28	9	9
AKT1	0.028	0.09	0.33	10	-10000	0	10
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.044	0.14	0.31	8	-0.43	18	26
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
FGR	0.013	0.087	0.33	1	-0.35	12	13
mol:Ca2+	0.02	0.13	0.3	9	-0.46	19	28
MYC	0.029	0.21	0.37	16	-0.67	25	41
SHC1	0.026	0.017	0.33	1	-10000	0	1
HRAS/GDP	0.038	0.063	-10000	0	-0.23	9	9
LRP1/PDGFRB/PDGFB	0.042	0.06	-10000	0	-0.28	12	12
GRB10	0.02	0.055	-10000	0	-0.47	5	5
PTPN11	0.027	0.005	-10000	0	-10000	0	0
GO:0007205	0.019	0.14	0.3	9	-0.47	19	28
PTEN	0.026	0.007	-10000	0	-10000	0	0
GRB2	0.027	0.005	-10000	0	-10000	0	0
GRB7	0.028	0.084	0.31	14	-0.47	7	21
PDGFB-D/PDGFRB/SHP2	0.032	0.054	-10000	0	-0.34	8	8
PDGFB-D/PDGFRB/GRB10	0.026	0.07	-10000	0	-0.34	14	14
cell cycle arrest	0.016	0.095	-10000	0	-0.4	18	18
HRAS	0.025	0.008	-10000	0	-10000	0	0
HIF1A	0.023	0.084	0.32	10	-10000	0	10
GAB1	0.019	0.13	0.36	4	-0.44	17	21
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.023	0.12	0.31	9	-0.44	13	22
PDGFB-D/PDGFRB	0.037	0.057	-10000	0	-0.3	9	9
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.032	0.05	-10000	0	-0.34	7	7
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.027	0.11	0.27	5	-0.43	11	16
positive regulation of MAPKKK cascade	0.031	0.054	-10000	0	-0.34	8	8
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
mol:IP3	0.019	0.14	0.3	9	-0.47	19	28
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.026	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.031	0.083	0.24	12	-0.34	16	28
SHB	0.024	0.009	-10000	0	-10000	0	0
BLK	-0.078	0.21	-10000	0	-0.45	85	85
PTPN2	0.026	0.008	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.031	0.057	-10000	0	-0.34	9	9
BCAR1	0.026	0.006	-10000	0	-10000	0	0
VAV2	0.02	0.14	0.34	8	-0.48	16	24
CBL	0.026	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.03	0.057	-10000	0	-0.32	10	10
LCK	0.01	0.1	0.33	1	-0.42	13	14
PDGFRB	0.017	0.074	-10000	0	-0.47	9	9
ACP1	0.026	0.006	-10000	0	-10000	0	0
HCK	0.002	0.14	0.35	1	-0.56	17	18
ABL1	0.017	0.12	0.27	15	-0.43	14	29
PDGFB-D/PDGFRB/CBL	0.013	0.15	0.34	4	-0.52	19	23
PTPN1	0.026	0.008	-10000	0	-10000	0	0
SNX15	0.027	0.005	-10000	0	-10000	0	0
STAT3	0.027	0.004	-10000	0	-10000	0	0
STAT1	0.029	0.019	0.21	4	-10000	0	4
cell proliferation	0.032	0.2	0.35	20	-0.6	25	45
SLA	0.009	0.088	0.21	1	-0.47	13	14
actin cytoskeleton reorganization	0.051	0.082	0.34	9	-0.24	5	14
SRC	0.014	0.074	0.34	1	-0.32	9	10
PI3K	0.005	0.037	-10000	0	-0.23	8	8
PDGFB-D/PDGFRB/GRB7/SHC	0.042	0.073	0.24	11	-0.28	14	25
SH2B2	0.029	0.021	0.21	5	-10000	0	5
PLCgamma1/SPHK1	0.044	0.14	0.31	8	-0.46	17	25
LYN	0.013	0.081	0.33	1	-0.36	9	10
LRP1	0.022	0.049	-10000	0	-0.47	4	4
SOS1	0.027	0.005	-10000	0	-10000	0	0
STAT5B	0.027	0.004	-10000	0	-10000	0	0
STAT5A	0.026	0.025	-10000	0	-0.47	1	1
NCK1-2/p130 Cas	0.055	0.058	-10000	0	-0.24	8	8
SPHK1	0.052	0.07	0.22	56	-0.48	1	57
EDG1	0.001	0.003	-10000	0	-10000	0	0
mol:DAG	0.019	0.14	0.3	9	-0.47	19	28
PLCG1	0.019	0.14	0.33	6	-0.48	19	25
NHERF/PDGFRB	0.049	0.06	-10000	0	-0.28	9	9
YES1	0.001	0.1	-10000	0	-0.44	14	14
cell migration	0.048	0.059	-10000	0	-0.28	9	9
SHC/Grb2/SOS1	0.056	0.057	-10000	0	-0.24	7	7
SLC9A3R2	0.027	0.006	-10000	0	-10000	0	0
SLC9A3R1	0.036	0.041	0.21	21	-10000	0	21
NHERF1-2/PDGFRB/PTEN	0.058	0.06	-10000	0	-0.26	9	9
FYN	-0.012	0.13	-10000	0	-0.42	30	30
DOK1	0.032	0.07	0.2	9	-0.26	8	17
HRAS/GTP	0.019	0.006	-10000	0	-10000	0	0
PDGFB	0.027	0.011	0.21	1	-10000	0	1
RAC1	0.022	0.16	0.34	12	-0.44	27	39
PRKCD	0.029	0.071	0.19	37	-0.27	9	46
FER	0.029	0.072	0.19	32	-0.26	10	42
MAPKKK cascade	0.028	0.094	0.39	9	-0.23	5	14
RASA1	0.03	0.07	0.19	40	-0.26	9	49
NCK1	0.026	0.006	-10000	0	-10000	0	0
NCK2	0.027	0.004	-10000	0	-10000	0	0
p62DOK/Csk	0.044	0.065	0.27	1	-0.24	8	9
PDGFB-D/PDGFRB/SHB	0.029	0.054	-10000	0	-0.33	8	8
chemotaxis	0.018	0.12	0.27	15	-0.42	14	29
STAT1-3-5/STAT1-3-5	0.047	0.055	-10000	0	-0.23	10	10
Bovine Papilomavirus E5/PDGFRB	0.012	0.054	-10000	0	-0.34	9	9
PTPRJ	0.026	0.007	-10000	0	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.026	0.01	-10000	0	-10000	0	0
HSPA8	0.026	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.02	0.14	-10000	0	-0.31	67	67
AKT1	0.027	0.017	-10000	0	-10000	0	0
GSC	0.02	0.062	-10000	0	-10000	0	0
NKX2-5	-0.001	0.012	-10000	0	-10000	0	0
muscle cell differentiation	-0.004	0.11	0.43	12	-10000	0	12
SMAD2-3/SMAD4/SP1	0.058	0.1	-10000	0	-0.3	15	15
SMAD4	0.009	0.054	-10000	0	-0.2	7	7
CBFB	0.027	0.006	-10000	0	-10000	0	0
SAP18	0.027	0.005	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.051	0.025	-10000	0	-10000	0	0
SMAD3/SMAD4/VDR	0.056	0.07	-10000	0	-0.37	2	2
MYC	-0.002	0.1	-10000	0	-0.47	18	18
CDKN2B	-0.14	0.3	-10000	0	-1.5	12	12
AP1	-0.05	0.17	-10000	0	-0.5	27	27
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.024	0.071	-10000	0	-0.35	4	4
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.008	0.079	-10000	0	-0.37	10	10
SP3	0.029	0.005	-10000	0	-10000	0	0
CREB1	0.027	0.006	-10000	0	-10000	0	0
FOXH1	0.074	0.091	0.24	91	-10000	0	91
SMAD3/SMAD4/GR	0.017	0.092	-10000	0	-0.31	16	16
GATA3	-0.008	0.12	0.33	2	-0.45	26	28
SKI/SIN3/HDAC complex/NCoR1	0.019	0.058	-10000	0	-0.42	3	3
MEF2C/TIF2	0.013	0.11	0.32	2	-0.37	19	21
endothelial cell migration	-0.015	0.15	1.2	6	-10000	0	6
MAX	0.026	0.006	-10000	0	-10000	0	0
RBBP7	0.027	0.004	-10000	0	-10000	0	0
RBBP4	0.028	0.002	-10000	0	-10000	0	0
RUNX2	0.028	0.031	0.21	4	-0.47	1	5
RUNX3	0.01	0.09	-10000	0	-0.47	14	14
RUNX1	0.026	0.006	-10000	0	-10000	0	0
CTBP1	0.027	0.016	0.33	1	-10000	0	1
NR3C1	0.012	0.081	-10000	0	-0.47	11	11
VDR	0.026	0.038	0.33	1	-0.47	2	3
CDKN1A	0.005	0.12	-10000	0	-0.88	4	4
KAT2B	0.024	0.026	-10000	0	-0.47	1	1
SMAD2/SMAD2/SMAD4/FOXH1	0.08	0.08	0.26	10	-0.24	6	16
DCP1A	0.026	0.007	-10000	0	-10000	0	0
SKI	0.027	0.003	-10000	0	-10000	0	0
SERPINE1	0.014	0.15	-10000	0	-1.2	6	6
SMAD3/SMAD4/ATF2	0.029	0.069	-10000	0	-0.22	5	5
SMAD3/SMAD4/ATF3	-0.025	0.15	-10000	0	-0.32	75	75
SAP30	0.027	0.006	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.044	0.025	-10000	0	-10000	0	0
JUN	-0.059	0.16	-10000	0	-0.49	27	27
SMAD3/SMAD4/IRF7	0.035	0.077	0.26	1	-0.24	6	7
TFE3	0.031	0.015	-10000	0	-0.19	1	1
COL1A2	-0.02	0.24	-10000	0	-0.9	27	27
mesenchymal cell differentiation	-0.029	0.072	0.21	9	-10000	0	9
DLX1	0.041	0.059	0.21	41	-10000	0	41
TCF3	0.027	0.005	-10000	0	-10000	0	0
FOS	-0.13	0.23	-10000	0	-0.48	124	124
SMAD3/SMAD4/Max	0.025	0.07	-10000	0	-0.22	5	5
Cbp/p300/SNIP1	0.049	0.02	-10000	0	-10000	0	0
ZBTB17	0.026	0.007	-10000	0	-10000	0	0
LAMC1	0.01	0.056	-10000	0	-0.38	2	2
TGIF2/HDAC complex/SMAD3/SMAD4	0.028	0.067	-10000	0	-0.2	8	8
IRF7	0.031	0.043	0.22	13	-0.47	1	14
ESR1	-0.052	0.18	-10000	0	-0.46	66	66
HNF4A	0.035	0.065	0.22	40	-10000	0	40
MEF2C	0.022	0.1	0.33	2	-0.43	13	15
SMAD2-3/SMAD4	0.041	0.074	-10000	0	-0.25	7	7
Cbp/p300/Src-1	0.048	0.022	-10000	0	-10000	0	0
IGHV3OR16-13	-0.001	0.064	-10000	0	-0.34	13	13
TGIF2/HDAC complex	0.026	0.007	-10000	0	-10000	0	0
CREBBP	0.025	0.009	-10000	0	-10000	0	0
SKIL	0.027	0.016	0.33	1	-10000	0	1
HDAC1	0.028	0.002	-10000	0	-10000	0	0
HDAC2	0.026	0.007	-10000	0	-10000	0	0
SNIP1	0.027	0.003	-10000	0	-10000	0	0
GCN5L2	0	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.046	0.069	-10000	0	-0.24	4	4
MSG1/HSC70	0.041	0.021	0.17	8	-10000	0	8
SMAD2	0.027	0.025	-10000	0	-10000	0	0
SMAD3	0.007	0.053	-10000	0	-0.17	10	10
SMAD3/E2F4-5/DP1/p107/SMAD4	0.018	0.039	-10000	0	-0.23	1	1
SMAD2/SMAD2/SMAD4	0.006	0.061	0.23	4	-0.23	4	8
NCOR1	0.025	0.009	-10000	0	-10000	0	0
NCOA2	0	0.11	-10000	0	-0.47	20	20
NCOA1	0.027	0.006	-10000	0	-10000	0	0
MYOD/E2A	0.03	0.01	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.07	0.1	-10000	0	-0.33	10	10
IFNB1	0.004	0.048	-10000	0	-0.29	2	2
SMAD3/SMAD4/MEF2C	0.043	0.12	-10000	0	-0.46	13	13
CITED1	0.03	0.027	0.21	8	-10000	0	8
SMAD2-3/SMAD4/ARC105	0.055	0.071	-10000	0	-0.24	5	5
RBL1	0.027	0.019	0.27	2	-10000	0	2
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.013	0.11	-10000	0	-0.53	11	11
RUNX1-3/PEBPB2	0.04	0.061	-10000	0	-0.28	13	13
SMAD7	-0.032	0.16	-10000	0	-0.51	21	21
MYC/MIZ-1	0.013	0.08	-10000	0	-0.34	18	18
SMAD3/SMAD4	0.004	0.074	-10000	0	-0.44	6	6
IL10	-0.006	0.15	0.24	2	-0.39	39	41
PIASy/HDAC complex	0.027	0.006	-10000	0	-10000	0	0
PIAS3	0.024	0.01	-10000	0	-10000	0	0
CDK2	0.026	0.008	-10000	0	-10000	0	0
IL5	-0.001	0.12	0.24	1	-0.28	39	40
CDK4	0.027	0.017	0.33	1	-10000	0	1
PIAS4	0.027	0.006	-10000	0	-10000	0	0
ATF3	-0.058	0.19	-10000	0	-0.47	70	70
SMAD3/SMAD4/SP1	0.039	0.095	-10000	0	-0.3	16	16
FOXG1	0.021	0.076	0.21	51	-10000	0	51
FOXO3	0.015	0.017	-10000	0	-10000	0	0
FOXO1	0.014	0.025	-10000	0	-0.35	1	1
FOXO4	0.016	0.018	-10000	0	-10000	0	0
heart looping	0.022	0.1	0.33	2	-0.43	13	15
CEBPB	0.024	0.028	-10000	0	-0.47	1	1
SMAD3/SMAD4/DLX1	0.04	0.081	-10000	0	-0.21	6	6
MYOD1	-0.016	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	0.037	0.08	0.26	2	-0.22	6	8
SMAD3/SMAD4/GATA3	0.006	0.12	0.27	2	-0.31	42	44
SnoN/SIN3/HDAC complex/NCoR1	0.027	0.016	0.33	1	-10000	0	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.049	0.089	-10000	0	-0.3	14	14
SMAD3/SMAD4/SP1-3	0.056	0.092	-10000	0	-0.29	11	11
MED15	0.027	0.006	-10000	0	-10000	0	0
SP1	0.023	0.042	-10000	0	-10000	0	0
SIN3B	0.028	0.003	-10000	0	-10000	0	0
SIN3A	0.027	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.077	0.087	0.25	6	-0.3	9	15
ITGB5	0.009	0.068	-10000	0	-0.29	6	6
TGIF/SIN3/HDAC complex/CtBP	0.031	0.049	-10000	0	-0.4	2	2
SMAD3/SMAD4/AR	-0.092	0.17	-10000	0	-0.3	152	152
AR	-0.15	0.24	-10000	0	-0.47	145	145
negative regulation of cell growth	-0.011	0.089	-10000	0	-0.29	16	16
SMAD3/SMAD4/MYOD	0.018	0.069	-10000	0	-0.2	8	8
E2F5	0.023	0.03	0.21	2	-0.47	1	3
E2F4	0.027	0.006	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.092	0.081	-10000	0	-0.26	1	1
SMAD2-3/SMAD4/FOXO1-3a-4	0.018	0.077	-10000	0	-0.4	10	10
TFDP1	0.026	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.036	0.18	-10000	0	-0.5	27	27
SMAD3/SMAD4/RUNX2	0.029	0.072	-10000	0	-0.21	9	9
TGIF2	0.026	0.007	-10000	0	-10000	0	0
TGIF1	0.025	0.008	-10000	0	-10000	0	0
ATF2	0.027	0.004	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.025	0.018	0.33	1	-10000	0	1
NFATC1	0.008	0.098	0.35	1	-0.34	9	10
NFATC2	-0.034	0.079	-10000	0	-0.23	19	19
NFATC3	0.011	0.034	-10000	0	-0.36	3	3
YWHAE	0.025	0.008	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.036	0.14	0.27	7	-0.36	37	44
Exportin 1/Ran/NUP214	0.044	0.019	-10000	0	-10000	0	0
mol:DAG	-0.003	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.029	0.13	0.24	1	-0.36	33	34
BCL2/BAX	0.024	0.071	-10000	0	-0.33	15	15
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.002	0.021	-10000	0	-10000	0	0
CaM/Ca2+	-0.002	0.021	-10000	0	-10000	0	0
BAX	0.027	0.004	-10000	0	-10000	0	0
MAPK14	0.024	0.004	-10000	0	-10000	0	0
BAD	0.027	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.026	0.13	0.24	5	-0.35	33	38
Calcineurin A alpha-beta B1/BCL2	0.008	0.093	-10000	0	-0.47	15	15
FKBP8	0.027	0.003	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.026	0.13	0.35	33	-0.24	5	38
KPNB1	0.027	0.005	-10000	0	-10000	0	0
KPNA2	0.029	0.022	0.24	4	-10000	0	4
XPO1	0.026	0.005	-10000	0	-10000	0	0
SFN	0.038	0.066	0.21	32	-0.47	3	35
MAP3K8	0.02	0.035	-10000	0	-0.47	2	2
NFAT4/CK1 alpha	0	0.036	-10000	0	-0.22	3	3
MEF2D/NFAT1/Cbp/p300	-0.12	0.17	-10000	0	-0.28	177	177
CABIN1	-0.036	0.14	0.27	7	-0.36	38	45
CALM1	0.022	0.009	-10000	0	-10000	0	0
RAN	0.026	0.005	-10000	0	-10000	0	0
MAP3K1	0.026	0.007	-10000	0	-10000	0	0
CAMK4	0.016	0.07	0.21	1	-0.47	8	9
mol:Ca2+	-0.008	0.008	-10000	0	-10000	0	0
MAPK3	0.027	0.006	-10000	0	-10000	0	0
YWHAH	0.027	0.006	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.039	0.015	-10000	0	-10000	0	0
YWHAB	0.025	0.008	-10000	0	-10000	0	0
MAPK8	0.019	0.043	-10000	0	-0.47	3	3
MAPK9	0.026	0.007	-10000	0	-10000	0	0
YWHAG	0.027	0.004	-10000	0	-10000	0	0
FKBP1A	0.026	0.006	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.004	0.11	0.33	1	-0.36	10	11
PRKCH	0.027	0.005	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0	0.035	-10000	0	-10000	0	0
CASP3	0.023	0.006	-10000	0	-10000	0	0
PIM1	0.027	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.006	0.013	-10000	0	-10000	0	0
apoptosis	0.016	0.023	0.19	1	-10000	0	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.032	0.049	0.19	1	-0.25	2	3
PRKCB	-0.11	0.22	-10000	0	-0.47	112	112
PRKCE	0.027	0.006	-10000	0	-10000	0	0
JNK2/NFAT4	0.023	0.041	-10000	0	-0.33	3	3
BAD/BCL-XL	0.036	0.018	0.24	1	-10000	0	1
PRKCD	0.026	0.007	-10000	0	-10000	0	0
NUP214	0.024	0.008	-10000	0	-10000	0	0
PRKCZ	0.019	0.043	-10000	0	-0.47	3	3
PRKCA	0.022	0.049	-10000	0	-0.47	4	4
PRKCG	0.012	0.046	0.23	13	-10000	0	13
PRKCQ	-0.011	0.13	0.24	4	-0.47	31	35
FKBP38/BCL2	0.024	0.071	-10000	0	-0.33	15	15
EP300	0.003	0.024	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.026	0.006	-10000	0	-10000	0	0
NFATc/JNK1	0.015	0.1	0.33	1	-0.37	4	5
CaM/Ca2+/FKBP38	0.009	0.027	-10000	0	-10000	0	0
FKBP12/FK506	0.02	0.005	-10000	0	-10000	0	0
CSNK1A1	-0.006	0.02	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.003	0.05	-10000	0	-0.29	8	8
NFATc/ERK1	0.022	0.094	0.34	1	-0.38	3	4
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.025	0.14	-10000	0	-0.36	35	35
NR4A1	-0.25	0.25	-10000	0	-0.46	222	222
GSK3B	0.022	0.007	-10000	0	-10000	0	0
positive T cell selection	0.011	0.034	-10000	0	-0.36	3	3
NFAT1/CK1 alpha	-0.029	0.066	-10000	0	-0.26	6	6
RCH1/ KPNB1	0.041	0.017	0.24	1	-10000	0	1
YWHAQ	0.026	0.006	-10000	0	-10000	0	0
PRKACA	0.024	0.004	-10000	0	-10000	0	0
AKAP5	0.029	0.019	0.21	4	-10000	0	4
MEF2D	0.004	0.024	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.021	0.012	-10000	0	-10000	0	0
NFATc/p38 alpha	0.018	0.097	0.34	1	-0.35	5	6
CREBBP	0.003	0.024	-10000	0	-10000	0	0
BCL2	0.008	0.093	-10000	0	-0.47	15	15

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.014	0.015	0.3	1	-10000	0	1
BAD/BCL-XL/YWHAZ	0.032	0.025	0.22	1	-10000	0	1
CDKN1B	0.019	0.052	-10000	0	-0.28	7	7
CDKN1A	0.015	0.057	-10000	0	-0.29	8	8
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.025	0.008	-10000	0	-10000	0	0
FOXO3	0.021	0.038	-10000	0	-0.28	3	3
AKT1	0.011	0.038	-10000	0	-0.28	6	6
BAD	0.027	0.003	-10000	0	-10000	0	0
AKT3	0.004	0.059	-10000	0	-0.3	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.018	0.053	-10000	0	-0.28	8	8
AKT1/ASK1	0.039	0.064	-10000	0	-0.28	8	8
BAD/YWHAZ	0.042	0.025	-10000	0	-10000	0	0
RICTOR	0.024	0.009	-10000	0	-10000	0	0
RAF1	0.025	0.018	0.33	1	-10000	0	1
JNK cascade	-0.036	0.061	0.27	8	-10000	0	8
TSC1	0.017	0.049	-10000	0	-0.28	6	6
YWHAZ	0.021	0.012	-10000	0	-10000	0	0
AKT1/RAF1	0.039	0.061	-10000	0	-0.28	7	7
EP300	0.027	0.006	-10000	0	-10000	0	0
mol:GDP	0.018	0.056	-10000	0	-0.28	11	11
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.018	0.05	-10000	0	-0.29	6	6
YWHAQ	0.026	0.006	-10000	0	-10000	0	0
TBC1D4	0.008	0.003	-10000	0	-10000	0	0
MAP3K5	0.025	0.025	-10000	0	-0.47	1	1
MAPKAP1	0.025	0.009	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.053	0.066	0.32	2	-0.23	9	11
YWHAH	0.027	0.006	-10000	0	-10000	0	0
AKT1S1	0.017	0.052	-10000	0	-0.28	8	8
CASP9	0.018	0.056	-10000	0	-0.29	8	8
YWHAB	0.025	0.008	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.041	0.068	0.25	1	-0.27	8	9
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.049	0.02	-10000	0	-10000	0	0
YWHAE	0.025	0.008	-10000	0	-10000	0	0
SRC	0.026	0.007	-10000	0	-10000	0	0
AKT2/p21CIP1	0.022	0.058	0.25	3	-0.28	4	7
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.016	0.029	-10000	0	-0.26	2	2
CHUK	0.019	0.045	-10000	0	-0.29	4	4
BAD/BCL-XL	0.038	0.061	0.27	1	-0.27	7	8
mTORC2	0.027	0.015	-10000	0	-10000	0	0
AKT2	0.015	0.004	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.06	0.082	0.27	8	-0.35	3	11
PDPK1	0.026	0.006	-10000	0	-10000	0	0
MDM2	0.029	0.071	0.26	3	-0.28	8	11
MAPKKK cascade	-0.039	0.06	0.28	7	-10000	0	7
MDM2/Cbp/p300	0.064	0.08	0.28	6	-0.27	6	12
TSC1/TSC2	0.018	0.044	0.24	1	-0.28	4	5
proteasomal ubiquitin-dependent protein catabolic process	0.061	0.077	0.26	6	-0.26	6	12
glucose import	-0.14	0.12	0.21	1	-0.25	236	237
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.021	0.041	0.2	3	-10000	0	3
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.14	0.13	0.21	1	-0.25	236	237
GSK3A	0.02	0.057	-10000	0	-0.29	7	7
FOXO1	0.015	0.054	-10000	0	-0.28	8	8
GSK3B	0.02	0.061	-10000	0	-0.29	8	8
SFN	0.038	0.066	0.21	32	-0.47	3	35
G1/S transition of mitotic cell cycle	0.031	0.071	0.25	4	-0.28	7	11
p27Kip1/14-3-3 family	0.033	0.045	-10000	0	-0.33	1	1
PRKACA	0.027	0.003	-10000	0	-10000	0	0
KPNA1	0.027	0.005	-10000	0	-10000	0	0
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
YWHAG	0.027	0.004	-10000	0	-10000	0	0
RHEB	0.027	0.004	-10000	0	-10000	0	0
CREBBP	0.026	0.007	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	0.11	0.13	0.59	1	-10000	0	1
PCK1	0.11	0.1	-10000	0	-10000	0	0
HNF4A	0.14	0.16	0.66	4	-10000	0	4
KCNJ11	0.097	0.24	-10000	0	-0.83	19	19
AKT1	0.093	0.11	-10000	0	-0.54	1	1
response to starvation	0.006	0.007	-10000	0	-10000	0	0
DLK1	0.096	0.26	0.62	2	-0.87	19	21
NKX2-1	0.18	0.17	0.38	119	-10000	0	119
ACADM	0.11	0.14	-10000	0	-0.8	1	1
TAT	0.1	0.1	-10000	0	-10000	0	0
CEBPB	0.028	0.026	-10000	0	-0.46	1	1
CEBPA	0.035	0.05	0.25	10	-0.47	2	12
TTR	0.092	0.17	0.57	6	-10000	0	6
PKLR	0.13	0.15	0.57	3	-10000	0	3
APOA1	0.16	0.17	0.67	2	-10000	0	2
CPT1C	0.11	0.14	0.57	1	-0.66	2	3
ALAS1	0.11	0.11	-10000	0	-10000	0	0
TFRC	0.15	0.13	0.51	2	-10000	0	2
FOXF1	-0.14	0.24	-10000	0	-0.47	140	140
NF1	0.031	0.008	-10000	0	-10000	0	0
HNF1A (dimer)	0.048	0.028	0.23	5	-10000	0	5
CPT1A	0.12	0.15	0.58	4	-1	1	5
HMGCS1	0.14	0.16	0.57	8	-0.51	1	9
NR3C1	0.025	0.082	-10000	0	-0.46	11	11
CPT1B	0.11	0.14	-10000	0	-1	1	1
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.041	0.014	-10000	0	-10000	0	0
GCK	0.072	0.26	-10000	0	-0.8	27	27
CREB1	0.033	0.011	-10000	0	-10000	0	0
IGFBP1	0.097	0.098	-10000	0	-10000	0	0
PDX1	0.14	0.12	-10000	0	-10000	0	0
UCP2	0.12	0.14	0.58	2	-10000	0	2
ALDOB	0.13	0.16	0.54	1	-0.56	1	2
AFP	0.012	0.092	-10000	0	-10000	0	0
BDH1	0.12	0.14	0.52	2	-10000	0	2
HADH	0.13	0.16	0.69	1	-10000	0	1
F2	0.15	0.17	0.67	1	-10000	0	1
HNF1A	0.048	0.028	0.23	5	-10000	0	5
G6PC	0.061	0.062	-10000	0	-10000	0	0
SLC2A2	0.13	0.12	-10000	0	-0.46	1	1
INS	-0.028	0.011	-10000	0	-10000	0	0
FOXA1	-0.009	0.16	-10000	0	-0.46	42	42
FOXA3	0.098	0.085	0.3	26	-10000	0	26
FOXA2	0.18	0.2	0.67	2	-0.63	1	3
ABCC8	0.12	0.15	-10000	0	-0.56	1	1
ALB	0.018	0.095	-10000	0	-10000	0	0

×

IFN-gamma 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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.078	0.063	0.32	2	-10000	0	2
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.028	0.014	0.21	2	-10000	0	2
STAT1 (dimer)/Cbp/p300	0.064	0.051	0.3	5	-10000	0	5
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.05	0.029	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.008	0.062	-10000	0	-0.22	9	9
CaM/Ca2+	0.075	0.058	0.29	2	-10000	0	2
RAP1A	0.028	0.003	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.041	0.041	0.29	1	-10000	0	1
AKT1	0.035	0.075	0.31	14	-0.23	1	15
MAP2K1	0.022	0.057	0.29	7	-10000	0	7
MAP3K11	0.025	0.057	0.29	7	-10000	0	7
IFNGR1	0.029	0.009	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.076	0.19	-10000	0	-0.36	111	111
Rap1/GTP	0.017	0.013	-10000	0	-10000	0	0
CRKL/C3G	0.036	0.017	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.081	0.066	0.29	2	-10000	0	2
CEBPB	0.048	0.1	0.31	7	-0.57	5	12
STAT3	0.027	0.004	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.073	0.12	-10000	0	-0.68	7	7
STAT1	0.026	0.056	0.29	6	-10000	0	6
CALM1	0.027	0.005	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.066	0.085	0.23	81	-10000	0	81
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	0.048	0.055	0.29	8	-10000	0	8
CEBPB/PTGES2/Cbp/p300	0.03	0.058	-10000	0	-0.34	5	5
mol:Ca2+	0.072	0.06	0.31	2	-10000	0	2
MAPK3	0.03	0.096	-10000	0	-0.71	4	4
STAT1 (dimer)	-0.002	0.088	-10000	0	-0.3	8	8
MAPK1	0.028	0.11	-10000	0	-0.74	5	5
JAK2	0.026	0.012	-10000	0	-10000	0	0
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
JAK1	0.03	0.008	-10000	0	-10000	0	0
CAMK2D	0.025	0.035	-10000	0	-0.47	2	2
DAPK1	0.04	0.09	0.28	4	-0.52	6	10
SMAD7	0.013	0.053	0.19	10	-0.17	3	13
CBL/CRKL/C3G	0.053	0.051	0.28	5	-10000	0	5
PI3K	0.064	0.056	0.26	2	-0.24	1	3
IFNG	0.066	0.085	0.23	81	-10000	0	81
apoptosis	0.03	0.091	0.27	1	-0.39	13	14
CAMK2G	0.027	0.006	-10000	0	-10000	0	0
STAT3 (dimer)	0.027	0.004	-10000	0	-10000	0	0
CAMK2A	-0.12	0.22	-10000	0	-0.47	118	118
CAMK2B	0.046	0.062	0.22	43	-10000	0	43
FRAP1	0.023	0.073	0.3	14	-0.22	1	15
PRKCD	0.035	0.075	0.31	14	-0.23	1	15
RAP1B	0.026	0.008	-10000	0	-10000	0	0
negative regulation of cell growth	-0.008	0.062	-10000	0	-0.22	9	9
PTPN2	0.026	0.007	-10000	0	-10000	0	0
EP300	0.027	0.006	-10000	0	-10000	0	0
IRF1	0.025	0.049	0.26	5	-10000	0	5
STAT1 (dimer)/PIASy	0.045	0.055	0.28	8	-10000	0	8
SOCS1	0.008	0.14	-10000	0	-1	7	7
mol:GDP	0.048	0.046	0.27	4	-10000	0	4
CASP1	0.008	0.061	0.18	8	-0.25	8	16
PTGES2	0.025	0.008	-10000	0	-10000	0	0
IRF9	0.031	0.036	0.16	3	-0.16	2	5
mol:PI-3-4-5-P3	0.045	0.043	0.2	2	-0.24	1	3
RAP1/GDP	0.038	0.028	-10000	0	-10000	0	0
CBL	0.023	0.056	0.29	6	-10000	0	6
MAP3K1	0.024	0.055	0.29	6	-10000	0	6
PIAS1	0.027	0.004	-10000	0	-10000	0	0
PIAS4	0.027	0.005	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.008	0.062	-10000	0	-0.22	9	9
PTPN11	0.023	0.053	0.3	4	-10000	0	4
CREBBP	0.026	0.007	-10000	0	-10000	0	0
RAPGEF1	0.025	0.009	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.027	0.006	-10000	0	-10000	0	0
HDAC4	0.025	0.008	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.018	0.051	-10000	0	-0.31	11	11
CDKN1A	-0.01	0.048	-10000	0	-0.69	2	2
KAT2B	0.025	0.025	-10000	0	-0.47	1	1
BAX	0.027	0.004	-10000	0	-10000	0	0
FOXO3	-0.006	0.003	-10000	0	-10000	0	0
FOXO1	0.024	0.026	-10000	0	-0.47	1	1
FOXO4	0.016	0.006	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.027	0.005	-10000	0	-10000	0	0
TAT	0.019	0.046	0.21	17	-10000	0	17
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.012	0.017	-10000	0	-0.34	1	1
PPARGC1A	-0.18	0.24	0.21	1	-0.47	164	165
FHL2	0.023	0.043	-10000	0	-0.47	3	3
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.037	0.012	-10000	0	-10000	0	0
HIST2H4A	0.018	0.051	0.31	11	-10000	0	11
SIRT1/FOXO3a	0.016	0.022	-10000	0	-10000	0	0
SIRT1	0.025	0.013	0.2	2	-10000	0	2
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.046	0.021	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.023	0.047	-10000	0	-0.2	6	6
apoptosis	-0.05	0.016	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.096	0.16	-10000	0	-0.28	164	164
p53/SIRT1	0.029	0.028	0.39	2	-10000	0	2
SIRT1/FOXO4	0.017	0.046	-10000	0	-0.2	7	7
FOXO1/FHL2/SIRT1	0.043	0.034	-10000	0	-0.24	4	4
HIST1H1E	0.018	0.022	0.21	3	-10000	0	3
SIRT1/p300	0.037	0.013	-10000	0	-10000	0	0
muscle cell differentiation	-0.029	0.023	0.29	1	-0.22	1	2
TP53	0.023	0.015	0.2	2	-10000	0	2
KU70/SIRT1/BAX	0.051	0.016	-10000	0	-10000	0	0
CREBBP	0.026	0.007	-10000	0	-10000	0	0
MEF2D	0.026	0.007	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.039	0.029	-10000	0	-10000	0	0
ACSS2	0.013	0.017	0.29	1	-10000	0	1
SIRT1/PCAF/MYOD	0.029	0.023	0.22	1	-0.29	1	2

×

IL1-mediated signaling events

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
UBC13/UEV1A	0.02	0.003	-10000	0	-10000	0	0
PRKCZ	0.024	0.043	-10000	0	-0.47	3	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.027	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.017	0.049	-10000	0	-0.25	2	2
IRAK/TOLLIP	0.029	0.011	-10000	0	-10000	0	0
IKBKB	0.025	0.009	-10000	0	-10000	0	0
IKBKG	0.027	0.004	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0.027	0.13	0.28	9	-0.34	40	49
IL1A	0.004	0.15	0.22	40	-0.47	34	74
IL1B	-0.005	0.094	0.43	2	-0.35	25	27
IRAK/TRAF6/p62/Atypical PKCs	0.056	0.04	-10000	0	-0.23	3	3
IL1R2	0.035	0.086	0.22	37	-0.47	7	44
IL1R1	0.027	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.008	0.067	0.24	1	-0.29	4	5
TOLLIP	0.025	0.008	-10000	0	-10000	0	0
TICAM2	0.025	0.026	-10000	0	-0.47	1	1
MAP3K3	0.026	0.006	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.018	0.004	-10000	0	-10000	0	0
IKK complex/ELKS	0.028	0.063	-10000	0	-0.3	1	1
JUN	-0.01	0.051	0.16	10	-0.21	17	27
MAP3K7	0.026	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.048	0.081	-10000	0	-0.24	23	23
IL1 alpha/IL1R1/IL1RAP/MYD88	0.05	0.1	0.27	5	-0.26	32	37
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.059	0.1	0.32	2	-0.24	32	34
IL1 beta fragment/IL1R1/IL1RAP	0.028	0.08	0.23	3	-0.27	23	26
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MAPK8	-0.003	0.042	0.17	12	-0.22	7	19
IRAK1	0.015	0.003	-10000	0	-10000	0	0
IL1RN/IL1R1	0.04	0.041	-10000	0	-0.3	4	4
IRAK4	0.027	0.004	-10000	0	-10000	0	0
PRKCI	0.026	0.007	-10000	0	-10000	0	0
TRAF6	0.026	0.008	-10000	0	-10000	0	0
PI3K	0.035	0.023	-10000	0	-0.34	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.02	0.058	0.29	1	-0.26	6	7
CHUK	0.027	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.028	0.08	0.23	3	-0.27	23	26
IL1 beta/IL1R2	0.018	0.1	0.22	3	-0.31	31	34
IRAK/TRAF6/TAK1/TAB1/TAB2	0.035	0.015	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.033	0.071	-10000	0	-0.42	1	1
IRAK3	0.013	0.081	-10000	0	-0.47	11	11
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.051	0.08	-10000	0	-0.24	22	22
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.012	0.075	0.2	1	-0.22	33	34
IL1 alpha/IL1R1/IL1RAP	0.038	0.11	0.27	5	-0.28	32	37
RELA	0.027	0.005	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.026	0.007	-10000	0	-10000	0	0
MYD88	0.026	0.006	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.044	0.024	-10000	0	-10000	0	0
IL1RAP	0.032	0.035	0.23	11	-10000	0	11
UBE2N	0.027	0.004	-10000	0	-10000	0	0
IRAK/TRAF6	0.019	0.06	-10000	0	-0.26	1	1
CASP1	0.015	0.073	-10000	0	-0.47	9	9
IL1RN/IL1R2	0.046	0.078	0.28	3	-0.36	9	12
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.04	0.079	0.24	3	-0.25	22	25
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.011	0.077	-10000	0	-0.32	6	6
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
IL1RN	0.029	0.053	0.21	11	-0.47	3	14
TRAF6/TAK1/TAB1/TAB2	0.036	0.014	-10000	0	-10000	0	0
MAP2K6	0.017	0.041	0.18	13	-0.23	5	18

×

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

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
BAG4	0.023	0.01	-10000	0	-10000	0	0
Caspase 8 (4 units)	0.032	0.079	-10000	0	-0.36	4	4
NEF	-0.007	0.051	-10000	0	-0.21	20	20
NFKBIA	0.022	0.03	-10000	0	-0.15	2	2
BIRC3	0.004	0.12	-10000	0	-0.49	19	19
CYCS	0.022	0.087	0.19	33	-0.27	15	48
RIPK1	0.026	0.007	-10000	0	-10000	0	0
CD247	0.013	0.071	0.21	1	-0.26	21	22
MAP2K7	0.028	0.13	-10000	0	-0.57	12	12
protein ubiquitination	0.026	0.076	0.23	2	-0.36	2	4
CRADD	0.027	0.004	-10000	0	-10000	0	0
DAXX	0.027	0.003	-10000	0	-10000	0	0
FAS	0.02	0.055	-10000	0	-0.47	5	5
BID	0.019	0.085	0.19	23	-0.28	17	40
NF-kappa-B/RelA/I kappa B alpha	0.046	0.07	-10000	0	-0.26	17	17
TRADD	0.027	0.006	-10000	0	-10000	0	0
MAP3K5	0.025	0.025	-10000	0	-0.47	1	1
CFLAR	0.027	0.006	-10000	0	-10000	0	0
FADD	0.03	0.037	0.33	6	-10000	0	6
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.046	0.07	-10000	0	-0.27	17	17
MAPK8	0.027	0.13	0.35	3	-0.55	11	14
APAF1	0.027	0.004	-10000	0	-10000	0	0
TRAF1	0.023	0.037	0.21	1	-0.47	2	3
TRAF2	0.025	0.009	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.024	0.088	0.2	22	-0.28	19	41
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.024	0.084	0.26	1	-0.41	4	5
CHUK	0.027	0.079	0.24	1	-0.39	2	3
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.065	0.055	-10000	0	-0.3	4	4
TCRz/NEF	0.009	0.073	-10000	0	-0.3	21	21
TNF	0.036	0.042	0.21	21	-10000	0	21
FASLG	-0.006	0.12	0.31	1	-0.49	21	22
NFKB1	0.022	0.03	-10000	0	-0.15	2	2
TNFR1A/BAG4/TNF-alpha	0.05	0.035	-10000	0	-10000	0	0
CASP6	0.029	0.13	-10000	0	-0.53	13	13
CASP7	0.015	0.15	0.34	2	-0.47	23	25
RELA	0.023	0.028	-10000	0	-10000	0	0
CASP2	0.027	0.004	-10000	0	-10000	0	0
CASP3	0.015	0.15	0.34	2	-0.45	26	28
TNFRSF1A	0.027	0.005	-10000	0	-10000	0	0
TNFR1A/BAG4	0.033	0.016	-10000	0	-10000	0	0
CASP8	0.026	0.006	-10000	0	-10000	0	0
CASP9	0.027	0.003	-10000	0	-10000	0	0
MAP3K14	0.026	0.087	0.25	1	-0.41	3	4
APAF-1/Caspase 9	0.015	0.099	-10000	0	-0.37	16	16
BCL2	0.019	0.13	0.33	3	-0.51	12	15

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.026	0.006	-10000	0	-10000	0	0
ITGB7	0.021	0.055	-10000	0	-0.47	5	5
ITGA4	0.013	0.085	0.21	1	-0.47	12	13
alpha4/beta7 Integrin	0.024	0.076	-10000	0	-0.33	17	17
alpha4/beta1 Integrin	0.027	0.065	-10000	0	-0.34	12	12

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.002	0.1	-10000	0	-0.41	17	17
KLHL20	0.009	0.086	0.2	3	-0.2	33	36
CYFIP2	0.014	0.077	-10000	0	-0.47	10	10
Rac1/GDP	0.026	0.091	0.27	10	-0.26	12	22
ENAH	0.003	0.1	-10000	0	-0.4	18	18
AP1M1	0.027	0.004	-10000	0	-10000	0	0
RAP1B	0.026	0.008	-10000	0	-10000	0	0
RAP1A	0.028	0.003	-10000	0	-10000	0	0
CTNNB1	0.027	0.006	-10000	0	-10000	0	0
CDC42/GTP	0.017	0.046	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.021	0.045	-10000	0	-0.14	28	28
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.045	0.073	-10000	0	-0.27	17	17
RAPGEF1	0.014	0.099	0.26	6	-0.37	16	22
CTNND1	0.027	0.005	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.009	0.1	-10000	0	-0.42	18	18
CRK	0.009	0.096	-10000	0	-0.39	16	16
E-cadherin/gamma catenin/alpha catenin	0.037	0.068	-10000	0	-0.3	14	14
alphaE/beta7 Integrin	0.032	0.043	-10000	0	-0.33	5	5
IQGAP1	0.027	0.004	-10000	0	-10000	0	0
NCKAP1	0.027	0.005	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.046	0.018	-10000	0	-10000	0	0
DLG1	0.004	0.098	-10000	0	-0.41	16	16
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0.029	-10000	0	-10000	0	0
MLLT4	0.026	0.006	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.046	0.031	-10000	0	-0.26	3	3
PI3K	0.004	0.038	-10000	0	-10000	0	0
ARF6	0.027	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.024	0.074	-10000	0	-0.36	14	14
TIAM1	0.023	0.043	-10000	0	-0.47	3	3
E-cadherin(dimer)/Ca2+	0.047	0.058	-10000	0	-0.24	13	13
AKT1	0.016	0.039	0.15	1	-10000	0	1
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
CDH1	0.01	0.087	-10000	0	-0.47	13	13
RhoA/GDP	0.027	0.092	0.28	10	-0.26	12	22
actin cytoskeleton organization	0.01	0.067	0.16	7	-0.16	14	21
CDC42/GDP	0.028	0.094	0.27	11	-0.26	12	23
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.01	0.051	-10000	0	-0.24	14	14
ITGB7	0.021	0.055	-10000	0	-0.47	5	5
RAC1	0.026	0.006	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.051	0.062	-10000	0	-0.26	13	13
E-cadherin/Ca2+/beta catenin/alpha catenin	0.034	0.053	-10000	0	-0.24	13	13
mol:GDP	0.014	0.1	0.28	11	-0.29	14	25
CDC42/GTP/IQGAP1	0.036	0.007	-10000	0	-10000	0	0
JUP	0.024	0.035	-10000	0	-0.47	2	2
p120 catenin/RhoA/GDP	0.031	0.092	0.28	7	-0.27	12	19
RAC1/GTP/IQGAP1	0.035	0.01	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.04	0.008	-10000	0	-10000	0	0
RHOA	0.026	0.006	-10000	0	-10000	0	0
CDC42	0.028	0.003	-10000	0	-10000	0	0
CTNNA1	0.027	0.005	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.013	0.055	0.15	13	-0.18	7	20
NME1	0.027	0.011	0.21	1	-10000	0	1
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	0.006	0.097	-10000	0	-0.41	17	17
regulation of cell-cell adhesion	0.01	0.039	-10000	0	-10000	0	0
WASF2	0.006	0.037	-10000	0	-10000	0	0
Rap1/GTP	0.027	0.062	0.28	2	-10000	0	2
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.052	0.078	-10000	0	-0.27	18	18
CCND1	0.013	0.064	0.16	12	-0.22	7	19
VAV2	-0.028	0.2	-10000	0	-0.56	38	38
RAP1/GDP	0.031	0.077	0.28	6	-10000	0	6
adherens junction assembly	0.006	0.094	-10000	0	-0.4	17	17
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.026	0.006	-10000	0	-10000	0	0
PIP5K1C	0.027	0.005	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.04	0.074	-10000	0	-0.26	18	18
E-cadherin/beta catenin	0.002	0.062	-10000	0	-0.32	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	0.002	0.1	-10000	0	-0.4	18	18
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
Rac1/GTP	-0.039	0.1	-10000	0	-0.32	35	35
E-cadherin/beta catenin/alpha catenin	0.039	0.062	-10000	0	-0.28	13	13
ITGAE	0.025	0.008	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.002	0.1	-10000	0	-0.42	18	18

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.29	0.23	-10000	0	-0.47	259	259
CLTC	0.019	0.07	-10000	0	-0.39	9	9
calcium ion-dependent exocytosis	0.014	0.03	0.21	2	-10000	0	2
Dynamin 2/GTP	0.027	0.008	-10000	0	-10000	0	0
EXOC4	0.027	0.005	-10000	0	-10000	0	0
CD59	0.014	0.047	-10000	0	-0.31	7	7
CPE	0.005	0.055	-10000	0	-0.28	14	14
CTNNB1	0.027	0.006	-10000	0	-10000	0	0
membrane fusion	0.015	0.017	-10000	0	-10000	0	0
CTNND1	0.018	0.031	0.19	13	-10000	0	13
DNM2	0.027	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.017	0.051	0.2	2	-0.28	5	7
TSHR	0.01	0.016	-10000	0	-10000	0	0
INS	-0.021	0.13	-10000	0	-0.47	30	30
BIN1	-0.033	0.16	-10000	0	-0.47	49	49
mol:Choline	0.015	0.017	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.015	0.006	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.027	0.005	-10000	0	-10000	0	0
mol:Ca2+	0.026	0.008	-10000	0	-10000	0	0
JUP	0.012	0.05	-10000	0	-0.3	8	8
ASAP2/amphiphysin II	0.012	0.099	-10000	0	-0.26	46	46
ARF6/GTP	0.02	0.004	-10000	0	-10000	0	0
CDH1	0.007	0.061	-10000	0	-0.31	8	8
clathrin-independent pinocytosis	0.02	0.004	-10000	0	-10000	0	0
MAPK8IP3	0.027	0.031	0.21	4	-0.47	1	5
positive regulation of endocytosis	0.02	0.004	-10000	0	-10000	0	0
EXOC2	0.026	0.007	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.037	0.039	-10000	0	-0.21	3	3
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.027	0.005	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.036	0.068	0.3	9	-0.26	1	10
positive regulation of phagocytosis	0.015	0.003	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.035	0.022	-10000	0	-0.28	1	1
ACAP1	0.017	0.027	-10000	0	-0.18	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.05	0.1	-10000	0	-0.39	9	9
clathrin heavy chain/ACAP1	0.021	0.063	0.25	1	-0.33	8	9
JIP4/KLC1	0.049	0.015	-10000	0	-10000	0	0
EXOC1	0.027	0.004	-10000	0	-10000	0	0
exocyst	0.023	0.027	-10000	0	-0.22	3	3
RALA/GTP	0.02	0.004	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.035	0.01	-10000	0	-10000	0	0
receptor recycling	0.02	0.004	-10000	0	-10000	0	0
CTNNA1	0.018	0.031	0.19	13	-10000	0	13
NME1	0.015	0.006	-10000	0	-10000	0	0
clathrin coat assembly	0.023	0.073	0.27	1	-0.38	9	10
IL2RA	0.013	0.066	-10000	0	-0.3	7	7
VAMP3	0.015	0.003	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.12	0.11	-10000	0	-0.35	14	14
EXOC6	0.027	0.005	-10000	0	-10000	0	0
PLD1	0.014	0.01	-10000	0	-10000	0	0
PLD2	0.015	0.011	0.13	1	-10000	0	1
EXOC5	0.027	0.004	-10000	0	-10000	0	0
PIP5K1C	0.015	0.035	0.2	1	-0.21	4	5
SDC1	0.012	0.052	-10000	0	-0.3	7	7
ARF6/GDP	0.025	0.007	-10000	0	-10000	0	0
EXOC7	0.027	0.005	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.038	0.07	0.27	1	-0.31	9	10
mol:Phosphatidic acid	0.015	0.017	-10000	0	-10000	0	0
endocytosis	-0.011	0.097	0.26	46	-10000	0	46
SCAMP2	0.027	0.004	-10000	0	-10000	0	0
ADRB2	-0.007	0.095	-10000	0	-0.36	11	11
EXOC3	0.023	0.01	-10000	0	-10000	0	0
ASAP2	0.027	0.006	-10000	0	-10000	0	0
Dynamin 2/GDP	0.03	0.01	-10000	0	-10000	0	0
KLC1	0.027	0.005	-10000	0	-10000	0	0
AVPR2	0.001	0.1	0.25	1	-0.4	10	11
RALA	0.028	0.016	0.33	1	-10000	0	1
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.037	0.071	0.29	3	-0.3	6	9

×

Signaling events mediated by PRL

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
CCNE1	0.062	0.085	0.25	64	-10000	0	64
mol:Halofuginone	0.004	0.001	-10000	0	-10000	0	0
ITGA1	0.027	0.006	-10000	0	-10000	0	0
CDKN1A	-0.005	0.073	-10000	0	-0.47	6	6
PRL-3/alpha Tubulin	0.036	0.013	-10000	0	-10000	0	0
mol:Ca2+	-0.053	0.1	-10000	0	-0.35	44	44
AGT	-0.03	0.16	0.21	3	-0.47	48	51
CCNA2	-0.043	0.1	0.38	1	-10000	0	1
TUBA1B	0.027	0.003	-10000	0	-10000	0	0
EGR1	-0.061	0.14	-10000	0	-0.32	92	92
CDK2/Cyclin E1	0.043	0.1	0.35	3	-0.45	6	9
MAPK3	0.013	0.005	-10000	0	-10000	0	0
PRL-2 /Rab GGTase beta	0.04	0.006	-10000	0	-10000	0	0
MAPK1	0.013	0.005	-10000	0	-10000	0	0
PTP4A1	-0.041	0.099	-10000	0	-10000	0	0
PTP4A3	0.025	0.009	-10000	0	-10000	0	0
PTP4A2	0.028	0.001	-10000	0	-10000	0	0
ITGB1	0.013	0.006	-10000	0	-10000	0	0
SRC	0.026	0.007	-10000	0	-10000	0	0
RAC1	0	0.048	-10000	0	-0.51	1	1
Rab GGTase beta/Rab GGTase alpha	0.039	0.01	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.021	0.11	-10000	0	-10000	0	0
RABGGTA	0.027	0.005	-10000	0	-10000	0	0
BCAR1	-0.016	0.007	-10000	0	-10000	0	0
RHOC	0.002	0.042	-10000	0	-10000	0	0
RHOA	-0.008	0.078	-10000	0	-0.4	11	11
cell motility	0.007	0.08	0.29	2	-0.29	10	12
PRL-1/alpha Tubulin	-0.021	0.11	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.035	0.015	-10000	0	-10000	0	0
ROCK1	0.01	0.077	0.29	2	-0.29	9	11
RABGGTB	0.027	0.004	-10000	0	-10000	0	0
CDK2	0.027	0.005	-10000	0	-10000	0	0
mitosis	-0.041	0.098	-10000	0	-10000	0	0
ATF5	0.029	0.019	0.21	4	-10000	0	4

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.028	0.056	-10000	0	-0.34	9	9
ATM	0.026	0.007	-10000	0	-10000	0	0
UBE2D3	0.027	0.004	-10000	0	-10000	0	0
PRKDC	0.025	0.008	-10000	0	-10000	0	0
ATR	0.026	0.006	-10000	0	-10000	0	0
UBE2L3	0.027	0.006	-10000	0	-10000	0	0
FANCD2	0.022	0.024	0.24	4	-10000	0	4
protein ubiquitination	0.07	0.07	-10000	0	-0.25	8	8
XRCC5	0.026	0.007	-10000	0	-10000	0	0
XRCC6	0.027	0.005	-10000	0	-10000	0	0
M/R/N Complex	0.044	0.023	-10000	0	-10000	0	0
MRE11A	0.027	0.006	-10000	0	-10000	0	0
DNA-PK	0.047	0.021	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.007	0.13	-10000	0	-0.52	21	21
FANCF	0.025	0.027	0.21	1	-0.47	1	2
BRCA1	0.028	0.01	0.21	1	-10000	0	1
CCNE1	0.062	0.085	0.25	64	-10000	0	64
CDK2/Cyclin E1	0.061	0.057	0.24	19	-10000	0	19
FANCG	0.025	0.008	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.031	0.054	-10000	0	-0.34	8	8
FANCE	0.028	0.01	0.21	1	-10000	0	1
FANCC	0.025	0.013	0.21	1	-10000	0	1
NBN	0.023	0.01	-10000	0	-10000	0	0
FANCA	0.04	0.049	0.22	27	-10000	0	27
DNA repair	0.018	0.092	0.28	7	-0.37	8	15
BRCA1/BARD1/ubiquitin	0.031	0.054	-10000	0	-0.34	8	8
BARD1/DNA-PK	0.054	0.05	-10000	0	-0.26	7	7
FANCL	0.027	0.011	0.21	1	-10000	0	1
mRNA polyadenylation	-0.028	0.056	0.34	9	-10000	0	9
BRCA1/BARD1/CTIP/M/R/N Complex	0.027	0.055	-10000	0	-0.26	1	1
BRCA1/BACH1/BARD1/TopBP1	0.043	0.051	-10000	0	-0.28	8	8
BRCA1/BARD1/P53	0.051	0.053	-10000	0	-0.26	8	8
BARD1/CSTF1/BRCA1	0.042	0.051	-10000	0	-0.28	8	8
BRCA1/BACH1	0.028	0.01	0.21	1	-10000	0	1
BARD1	0.015	0.073	-10000	0	-0.47	9	9
PCNA	0.027	0.011	0.21	1	-10000	0	1
BRCA1/BARD1/UbcH5C	0.045	0.05	-10000	0	-0.28	8	8
BRCA1/BARD1/UbcH7	0.043	0.051	-10000	0	-0.28	8	8
BRCA1/BARD1/RAD51/PCNA	0.088	0.082	-10000	0	-0.27	8	8
BARD1/DNA-PK/P53	0.057	0.054	-10000	0	-0.24	7	7
BRCA1/BARD1/Ubiquitin	0.031	0.054	-10000	0	-0.34	8	8
BRCA1/BARD1/CTIP	0.034	0.046	-10000	0	-0.26	8	8
FA complex	0.021	0.064	0.22	1	-0.26	10	11
BARD1/EWS	0.029	0.056	-10000	0	-0.34	9	9
RBBP8	0.014	0.005	-10000	0	-10000	0	0
TP53	0.025	0.008	-10000	0	-10000	0	0
TOPBP1	0.027	0.006	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.049	0.052	0.26	8	-10000	0	8
BRCA1/BARD1	0.078	0.074	-10000	0	-0.25	8	8
CSTF1	0.026	0.007	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.011	0.052	-10000	0	-0.33	9	9
CDK2	0.027	0.005	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.093	0.09	0.21	144	-10000	0	144
RAD50	0.027	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.031	0.054	-10000	0	-0.34	8	8
EWSR1	0.026	0.006	-10000	0	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.046	0.08	0.36	1	-10000	0	1
CRKL	0.025	0.052	0.29	4	-10000	0	4
mol:DAG	0.038	0.047	0.28	1	-10000	0	1
HRAS	0.042	0.076	0.31	15	-10000	0	15
MAPK8	0.029	0.064	0.22	23	-0.28	3	26
RAP1A	0.026	0.053	0.29	4	-10000	0	4
GAB1	0.026	0.052	0.29	4	-10000	0	4
MAPK14	0.032	0.059	0.21	30	-10000	0	30
EPO	0.042	0.057	0.23	31	-10000	0	31
PLCG1	0.039	0.047	0.28	1	-10000	0	1
EPOR/TRPC2/IP3 Receptors	0.033	0.031	0.24	8	-10000	0	8
RAPGEF1	0.025	0.009	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.032	0.11	0.23	1	-0.3	35	36
GAB1/SHC/GRB2/SOS1	0.052	0.047	0.27	2	-10000	0	2
EPO/EPOR (dimer)	0.053	0.044	0.21	5	-10000	0	5
IRS2	0.016	0.07	0.29	4	-0.24	14	18
STAT1	0.045	0.063	0.27	2	-10000	0	2
STAT5B	0.042	0.054	0.28	1	-10000	0	1
cell proliferation	0.02	0.07	0.22	32	-0.26	3	35
GAB1/SHIP/PIK3R1/SHP2/SHC	0.036	0.044	-10000	0	-0.28	1	1
TEC	0.026	0.052	0.29	4	-10000	0	4
SOCS3	-0.021	0.15	-10000	0	-0.47	39	39
STAT1 (dimer)	0.044	0.062	0.27	2	-10000	0	2
JAK2	0.025	0.013	-10000	0	-10000	0	0
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
EPO/EPOR (dimer)/JAK2	0.072	0.059	-10000	0	-10000	0	0
EPO/EPOR	0.053	0.044	0.21	5	-10000	0	5
LYN	0.025	0.012	-10000	0	-10000	0	0
TEC/VAV2	0.038	0.048	0.28	2	-0.22	1	3
elevation of cytosolic calcium ion concentration	0.033	0.031	0.24	8	-10000	0	8
SHC1	0.026	0.017	0.33	1	-10000	0	1
EPO/EPOR (dimer)/LYN	0.063	0.045	0.23	1	-10000	0	1
mol:IP3	0.038	0.047	0.28	1	-10000	0	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.035	0.082	0.29	6	-0.24	18	24
SH2B3	0.028	0.011	-10000	0	-10000	0	0
NFKB1	0.032	0.059	0.21	29	-10000	0	29
EPO/EPOR (dimer)/JAK2/SOCS3	-0.006	0.075	0.19	1	-0.22	37	38
PTPN6	0.026	0.052	0.31	4	-10000	0	4
TEC/VAV2/GRB2	0.048	0.051	0.29	2	-0.22	1	3
EPOR	0.033	0.032	0.24	8	-10000	0	8
INPP5D	0.018	0.06	-10000	0	-0.47	6	6
mol:GDP	0.051	0.048	0.27	2	-10000	0	2
SOS1	0.027	0.005	-10000	0	-10000	0	0
PLCG2	0.026	0.039	0.21	3	-0.47	2	5
CRKL/CBL/C3G	0.047	0.049	0.29	2	-10000	0	2
VAV2	0.024	0.052	0.29	4	-0.22	1	5
CBL	0.026	0.051	0.29	4	-10000	0	4
SHC/Grb2/SOS1	0.037	0.038	-10000	0	-10000	0	0
STAT5A	0.041	0.057	0.28	1	-0.28	1	2
GRB2	0.027	0.005	-10000	0	-10000	0	0
STAT5 (dimer)	0.056	0.079	0.29	1	-0.3	11	12
LYN/PLCgamma2	0.037	0.026	-10000	0	-0.34	1	1
PTPN11	0.027	0.005	-10000	0	-10000	0	0
BTK	0.014	0.077	0.29	4	-0.24	20	24
BCL2	0.031	0.18	0.37	2	-0.82	15	17

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.01	0.064	-10000	0	-0.32	14	14
CRKL	0.028	0.014	0.21	2	-10000	0	2
Rac1/GDP	0.02	0.005	-10000	0	-10000	0	0
DOCK1	0.024	0.035	-10000	0	-0.47	2	2
ITGA4	0.013	0.085	0.21	1	-0.47	12	13
alpha4/beta7 Integrin/MAdCAM1	0.052	0.072	-10000	0	-0.26	17	17
EPO	0.033	0.057	0.22	31	-10000	0	31
alpha4/beta7 Integrin	0.024	0.076	-10000	0	-0.33	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.008	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.027	0.065	-10000	0	-0.34	12	12
EPO/EPOR (dimer)	0.05	0.04	0.24	2	-10000	0	2
lamellipodium assembly	0.015	0.079	-10000	0	-0.44	7	7
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
PI3K	0.035	0.023	-10000	0	-0.34	1	1
ARF6	0.027	0.005	-10000	0	-10000	0	0
JAK2	0.017	0.054	-10000	0	-0.28	11	11
PXN	0.027	0.004	-10000	0	-10000	0	0
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
MADCAM1	0.028	0.038	0.21	14	-10000	0	14
cell adhesion	0.05	0.071	-10000	0	-0.26	17	17
CRKL/CBL	0.038	0.015	-10000	0	-10000	0	0
ITGB1	0.026	0.006	-10000	0	-10000	0	0
SRC	0.005	0.084	0.19	15	-0.3	22	37
ITGB7	0.021	0.055	-10000	0	-0.47	5	5
RAC1	0.026	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.029	0.098	-10000	0	-0.35	23	23
p130Cas/Crk/Dock1	0.031	0.088	0.36	1	-0.27	19	20
VCAM1	0.008	0.1	0.21	2	-0.47	17	19
RHOA	0.026	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.052	0.06	-10000	0	-0.26	12	12
BCAR1	-0.014	0.079	0.2	15	-0.29	21	36
EPOR	0.031	0.029	0.23	8	-10000	0	8
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.026	0.007	-10000	0	-10000	0	0
GIT1	0.026	0.006	-10000	0	-10000	0	0
Rac1/GTP	0.015	0.081	-10000	0	-0.46	7	7

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.04	0.17	-10000	0	-0.47	55	55
HRAS	0.025	0.008	-10000	0	-10000	0	0
EGFR	0.021	0.085	0.33	8	-0.47	9	17
AKT	0.034	0.091	0.24	11	-0.27	13	24
FOXO3	0.026	0.007	-10000	0	-10000	0	0
AKT1	0.027	0.005	-10000	0	-10000	0	0
FOXO1	0.024	0.026	-10000	0	-0.47	1	1
AKT3	0.01	0.09	-10000	0	-0.47	14	14
FOXO4	0.028	0.01	0.21	1	-10000	0	1
MET	0.029	0.022	0.33	2	-10000	0	2
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
PIK3CB	0.026	0.006	-10000	0	-10000	0	0
NRAS	0.028	0.002	-10000	0	-10000	0	0
PIK3CG	0.013	0.085	0.21	2	-0.47	12	14
PIK3R3	0.027	0.004	-10000	0	-10000	0	0
PIK3R2	0.027	0.003	-10000	0	-10000	0	0
NF1	0.026	0.006	-10000	0	-10000	0	0
RAS	0.011	0.072	0.2	6	-0.23	10	16
ERBB2	0.037	0.053	0.33	13	-10000	0	13
proliferation/survival/translation	-0.037	0.068	0.25	7	-0.24	2	9
PI3K	0.026	0.075	0.21	23	-0.19	8	31
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
KRAS	0.027	0.016	0.33	1	-10000	0	1
FOXO	0.06	0.06	0.23	13	-0.11	1	14
AKT2	0.027	0.006	-10000	0	-10000	0	0
PTEN	0.026	0.007	-10000	0	-10000	0	0

×

E-cadherin signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.037	0.068	-9999	-0.3	14	14
E-cadherin/beta catenin	0.025	0.067	-9999	-0.34	13	13
CTNNB1	0.027	0.006	-9999	-10000	0	0
JUP	0.024	0.035	-9999	-0.47	2	2
CDH1	0.01	0.087	-9999	-0.47	13	13

×

mTOR signaling pathway

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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.027	0.004	-10000	0	-10000	0	0
mol:PIP3	-0.005	0.051	-10000	0	-0.24	8	8
FRAP1	0.016	0.049	-10000	0	-0.41	3	3
AKT1	0.004	0.058	0.2	2	-0.23	6	8
INSR	0.027	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.027	0.009	-10000	0	-10000	0	0
mol:GTP	0.027	0.059	0.26	2	-10000	0	2
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.012	0.02	-10000	0	-10000	0	0
TSC2	0.027	0.006	-10000	0	-10000	0	0
RHEB/GDP	0.011	0.038	-10000	0	-10000	0	0
TSC1	0.025	0.009	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.005	0.073	-10000	0	-0.22	37	37
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.026	0.029	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.027	0.006	-10000	0	-10000	0	0
RPS6KB1	0.025	0.051	0.23	2	-10000	0	2
MAP3K5	0.003	0.046	0.2	7	-0.19	14	21
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
apoptosis	0.004	0.046	0.2	7	-0.19	14	21
mol:LY294002	0	0	-10000	0	-0.001	35	35
EIF4B	0.024	0.05	0.26	4	-10000	0	4
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.037	0.045	0.24	1	-10000	0	1
eIF4E/eIF4G1/eIF4A1	0.017	0.028	-10000	0	-0.25	3	3
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.019	0.068	-10000	0	-0.21	23	23
mTOR/RHEB/GTP/Raptor/GBL	0.01	0.044	0.18	8	-10000	0	8
FKBP1A	0.027	0.006	-10000	0	-10000	0	0
RHEB/GTP	0.03	0.052	0.22	1	-10000	0	1
mol:Amino Acids	0	0	-10000	0	-0.001	35	35
FKBP12/Rapamycin	0.02	0.005	-10000	0	-10000	0	0
PDPK1	-0.008	0.057	0.16	18	-0.25	6	24
EIF4E	0.027	0.004	-10000	0	-10000	0	0
ASK1/PP5C	0.022	0.12	-10000	0	-0.54	15	15
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.013	0.033	-10000	0	-10000	0	0
TSC1/TSC2	0.03	0.063	0.28	2	-10000	0	2
tumor necrosis factor receptor activity	0	0	0.001	35	-10000	0	35
RPS6	0.024	0.01	-10000	0	-10000	0	0
PPP5C	0.027	0.004	-10000	0	-10000	0	0
EIF4G1	0.026	0.006	-10000	0	-10000	0	0
IRS1	-0.013	0.072	-10000	0	-0.23	37	37
INS	-0.016	0.005	-10000	0	-10000	0	0
PTEN	0.026	0.007	-10000	0	-10000	0	0
PDK2	-0.008	0.056	0.19	2	-0.25	6	8
EIF4EBP1	-0.029	0.26	-10000	0	-1	25	25
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
PPP2R5D	0.019	0.05	-10000	0	-0.37	3	3
peptide biosynthetic process	0.011	0.013	0.18	2	-10000	0	2
RHEB	0.027	0.004	-10000	0	-10000	0	0
EIF4A1	0.025	0.008	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.003	13	-10000	0	13
EEF2	0.011	0.013	0.18	2	-10000	0	2
eIF4E/4E-BP1	-0.017	0.24	-10000	0	-0.96	25	25

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.004	0.025	0.51	1	-10000	0	1
SNTA1	0.025	0.009	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.007	0.03	0.36	2	-10000	0	2
MAPK12	-0.002	0.029	0.18	1	-0.25	5	6
CCND1	0.011	0.071	0.29	1	-0.4	8	9
p38 gamma/SNTA1	0.021	0.048	0.19	15	-0.23	6	21
MAP2K3	0.025	0.008	-10000	0	-10000	0	0
PKN1	0.026	0.025	-10000	0	-0.47	1	1
G2/M transition checkpoint	0.007	0.05	0.2	17	-0.25	5	22
MAP2K6	0	0.033	-10000	0	-0.27	6	6
MAPT	-0.012	0.096	0.25	7	-0.3	33	40
MAPK13	0.015	0.028	0.56	1	-10000	0	1
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.007	0.016	-10000	0	-0.31	1	1

×

Syndecan-3-mediated signaling events

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
CTTN	0.026	0.017	0.33	1	-10000	0	1
Syndecan-3/Src/Cortactin	0.018	0.12	-10000	0	-0.48	2	2
Syndecan-3/Neurocan	0.033	0.049	0.31	1	-0.48	2	3
POMC	0.025	0.063	0.21	10	-0.47	5	15
EGFR	0.021	0.085	0.33	8	-0.47	9	17
Syndecan-3/EGFR	0.03	0.058	0.26	3	-0.39	2	5
AGRP	0.008	0.031	0.25	3	-10000	0	3
NCSTN	0.024	0.01	-10000	0	-10000	0	0
PSENEN	0.027	0.006	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0.027	0.004	-10000	0	-10000	0	0
APH1A	0.025	0.009	-10000	0	-10000	0	0
NCAN	0.013	0.042	0.22	11	-10000	0	11
long-term memory	0.045	0.057	-10000	0	-0.55	2	2
Syndecan-3/IL8	0	0.096	-10000	0	-0.69	2	2
PSEN1	0.027	0.005	-10000	0	-10000	0	0
Src/Cortactin	0.035	0.018	0.24	1	-10000	0	1
FYN	0.022	0.043	-10000	0	-0.47	3	3
limb bud formation	0.01	0.036	-10000	0	-0.49	2	2
MC4R	0.002	0.031	0.21	5	-10000	0	5
SRC	0.026	0.007	-10000	0	-10000	0	0
PTN	-0.062	0.2	0.21	20	-0.47	80	100
FGFR/FGF/Syndecan-3	0.01	0.037	-10000	0	-0.49	2	2
neuron projection morphogenesis	0	0.11	0.34	3	-0.47	2	5
Syndecan-3/AgRP	0.029	0.044	-10000	0	-0.48	2	2
Syndecan-3/AgRP/MC4R	0.045	0.052	0.31	1	-0.47	2	3
Fyn/Cortactin	0.033	0.032	0.24	1	-0.34	2	3
SDC3	0.01	0.037	-10000	0	-0.5	2	2
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	0	0.095	-10000	0	-0.67	2	2
IL8	-0.041	0.17	0.21	1	-0.47	56	57
Syndecan-3/Fyn/Cortactin	0.046	0.059	-10000	0	-0.56	2	2
Syndecan-3/CASK	0.008	0.037	-10000	0	-0.47	2	2
alpha-MSH/MC4R	0.032	0.049	-10000	0	-0.34	5	5
Gamma Secretase	0.062	0.036	-10000	0	-10000	0	0

×

Class I PI3K 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.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.027	0.045	0.3	3	-10000	0	3
DAPP1	0.007	0.11	0.28	5	-0.32	18	23
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.02	0.17	0.32	2	-0.47	29	31
mol:DAG	0.008	0.091	0.2	24	-0.23	16	40
HRAS	0.027	0.009	-10000	0	-10000	0	0
RAP1A	0.029	0.005	-10000	0	-10000	0	0
ARF5/GDP	0.038	0.068	0.22	1	-0.3	5	6
PLCG2	0.026	0.039	0.21	3	-0.47	2	5
PLCG1	0.026	0.007	-10000	0	-10000	0	0
ARF5	0.027	0.004	-10000	0	-10000	0	0
mol:GTP	-0.003	0.042	0.31	2	-10000	0	2
ARF1/GTP	0.009	0.045	0.27	4	-10000	0	4
RHOA	0.026	0.006	-10000	0	-10000	0	0
YES1	0.025	0.008	-10000	0	-10000	0	0
RAP1A/GTP	0.021	0.032	-10000	0	-10000	0	0
ADAP1	-0.005	0.044	0.29	2	-0.24	2	4
ARAP3	-0.003	0.042	0.3	2	-10000	0	2
INPPL1	0.026	0.006	-10000	0	-10000	0	0
PREX1	0.026	0.008	-10000	0	-10000	0	0
ARHGEF6	0.024	0.043	-10000	0	-0.47	3	3
ARHGEF7	0.026	0.006	-10000	0	-10000	0	0
ARF1	0.027	0.003	-10000	0	-10000	0	0
NRAS	0.029	0.005	-10000	0	-10000	0	0
FYN	0.022	0.043	-10000	0	-0.47	3	3
ARF6	0.027	0.005	-10000	0	-10000	0	0
FGR	0.025	0.035	-10000	0	-0.47	2	2
mol:Ca2+	0.008	0.059	0.19	14	-0.15	2	16
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.023	0.043	-10000	0	-0.47	3	3
ZAP70	0.01	0.091	0.21	1	-0.47	14	15
mol:IP3	0.006	0.075	0.23	14	-0.18	12	26
LYN	0.025	0.008	-10000	0	-10000	0	0
ARF1/GDP	0.038	0.068	0.22	1	-0.3	5	6
RhoA/GDP	0.041	0.048	0.23	1	-10000	0	1
PDK1/Src/Hsp90	0.049	0.02	-10000	0	-10000	0	0
BLNK	0.011	0.087	-10000	0	-0.47	13	13
actin cytoskeleton reorganization	0.033	0.075	0.28	4	-0.28	2	6
SRC	0.026	0.007	-10000	0	-10000	0	0
PLEKHA2	-0.007	0.024	-10000	0	-0.28	3	3
RAC1	0.026	0.006	-10000	0	-10000	0	0
PTEN	0.024	0.013	-10000	0	-10000	0	0
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
ARF6/GTP	0.024	0.04	0.29	2	-10000	0	2
RhoA/GTP	-0.004	0.043	0.3	2	-10000	0	2
Src family/SYK family/BLNK-LAT	-0.009	0.11	-10000	0	-0.32	29	29
BLK	-0.011	0.14	0.21	15	-0.47	30	45
PDPK1	0.026	0.006	-10000	0	-10000	0	0
CYTH1	-0.005	0.039	0.29	2	-10000	0	2
HCK	0.014	0.08	0.21	5	-0.47	10	15
CYTH3	-0.004	0.04	0.29	2	-10000	0	2
CYTH2	-0.004	0.041	0.29	2	-10000	0	2
KRAS	0.028	0.016	0.31	1	-10000	0	1
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.002	0.094	0.22	2	-0.4	17	19
SGK1	-0.002	0.11	0.22	2	-0.39	24	26
INPP5D	0.018	0.06	-10000	0	-0.47	6	6
mol:GDP	0.025	0.067	0.22	1	-0.3	6	7
SOS1	0.027	0.005	-10000	0	-10000	0	0
SYK	0.02	0.049	-10000	0	-0.47	4	4
ARF6/GDP	0.031	0.049	0.26	4	-10000	0	4
mol:PI-3-4-5-P3	-0.004	0.04	0.29	2	-10000	0	2
ARAP3/RAP1A/GTP	0.021	0.032	-10000	0	-10000	0	0
VAV1	0.008	0.097	0.21	2	-0.47	16	18
mol:PI-3-4-P2	0.011	0.03	-10000	0	-0.34	3	3
RAS family/GTP/PI3K Class I	0.045	0.039	-10000	0	-10000	0	0
PLEKHA1	-0.007	0.024	-10000	0	-0.28	3	3
Rac1/GDP	0.036	0.066	-10000	0	-0.3	5	5
LAT	0.027	0.011	0.21	1	-10000	0	1
Rac1/GTP	0.018	0.063	-10000	0	-0.3	6	6
ITK	-0.023	0.075	0.29	2	-0.24	34	36
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.002	0.11	0.23	22	-0.31	19	41
LCK	0.024	0.051	0.21	2	-0.47	4	6
BTK	-0.015	0.065	0.29	2	-0.24	19	21

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	0.067	0.11	-10000	0	-0.6	1	1
RAD9A	0.03	0.026	0.23	6	-10000	0	6
AP1	-0.079	0.19	-10000	0	-0.36	120	120
IFNAR2	0.03	0.009	-10000	0	-10000	0	0
AKT1	-0.011	0.082	-10000	0	-0.37	5	5
ER alpha/Oestrogen	-0.036	0.13	-10000	0	-0.33	66	66
NFX1/SIN3/HDAC complex	0.039	0.035	-10000	0	-0.24	2	2
EGF	0.038	0.045	0.21	24	-10000	0	24
SMG5	0.026	0.007	-10000	0	-10000	0	0
SMG6	0.025	0.008	-10000	0	-10000	0	0
SP3/HDAC2	0.044	0.016	-10000	0	-10000	0	0
TERT/c-Abl	0.064	0.11	-10000	0	-0.56	1	1
SAP18	0.027	0.005	-10000	0	-10000	0	0
MRN complex	0.044	0.023	-10000	0	-10000	0	0
WT1	0.049	0.066	0.22	50	-10000	0	50
WRN	0.024	0.01	-10000	0	-10000	0	0
SP1	0.032	0.01	-10000	0	-10000	0	0
SP3	0.029	0.006	-10000	0	-10000	0	0
TERF2IP	0.026	0.006	-10000	0	-10000	0	0
Telomerase/Nucleolin	0.075	0.1	-10000	0	-0.52	1	1
Mad/Max	0.043	0.015	-10000	0	-10000	0	0
TERT	0.067	0.11	-10000	0	-0.62	1	1
CCND1	0.071	0.19	-10000	0	-1.1	7	7
MAX	0.029	0.006	-10000	0	-10000	0	0
RBBP7	0.028	0.004	-10000	0	-10000	0	0
RBBP4	0.028	0.002	-10000	0	-10000	0	0
TERF2	0.024	0.012	-10000	0	-10000	0	0
PTGES3	0.027	0.004	-10000	0	-10000	0	0
SIN3A	0.028	0.004	-10000	0	-10000	0	0
Telomerase/911	0.06	0.053	0.29	1	-10000	0	1
CDKN1B	0.028	0.028	0.24	6	-10000	0	6
RAD1	0.024	0.009	-10000	0	-10000	0	0
XRCC5	0.026	0.007	-10000	0	-10000	0	0
XRCC6	0.027	0.005	-10000	0	-10000	0	0
SAP30	0.027	0.006	-10000	0	-10000	0	0
TRF2/PARP2	0.038	0.013	-10000	0	-10000	0	0
UBE3A	0.028	0.006	-10000	0	-10000	0	0
JUN	0.012	0.091	-10000	0	-0.47	14	14
E6	0.002	0.002	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.024	0.007	-10000	0	-10000	0	0
FOS	-0.12	0.23	-10000	0	-0.46	124	124
IFN-gamma/IRF1	0.073	0.06	0.25	6	-10000	0	6
PARP2	0.027	0.005	-10000	0	-10000	0	0
BLM	0.033	0.034	0.22	12	-10000	0	12
Telomerase	0.024	0.067	-10000	0	-0.5	2	2
IRF1	0.032	0.007	-10000	0	-10000	0	0
ESR1	-0.053	0.18	-10000	0	-0.47	66	66
KU/TER	0.038	0.011	-10000	0	-10000	0	0
ATM/TRF2	0.037	0.013	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.042	0.044	-10000	0	-0.32	1	1
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.042	0.045	-10000	0	-0.33	1	1
HDAC1	0.028	0.002	-10000	0	-10000	0	0
HDAC2	0.03	0.011	-10000	0	-10000	0	0
ATM	0.011	0.01	-10000	0	-10000	0	0
SMAD3	0.012	0.005	-10000	0	-10000	0	0
ABL1	0.025	0.009	-10000	0	-10000	0	0
MXD1	0.029	0.011	0.22	1	-10000	0	1
MRE11A	0.027	0.006	-10000	0	-10000	0	0
HUS1	0.027	0.005	-10000	0	-10000	0	0
RPS6KB1	0.026	0.006	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	0.066	0.12	-10000	0	-0.53	1	1
NR2F2	0.022	0.025	-10000	0	-0.47	1	1
MAPK3	0.005	0.013	-10000	0	-10000	0	0
MAPK1	0.004	0.014	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.026	0.005	-10000	0	-10000	0	0
NFKB1	0.027	0.004	-10000	0	-10000	0	0
HNRNPC	0.027	0.005	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.011	0.01	-10000	0	-10000	0	0
NBN	0.023	0.01	-10000	0	-10000	0	0
EGFR	0.023	0.085	0.33	8	-0.46	9	17
mol:Oestrogen	0.001	0.001	-10000	0	-10000	0	0
EGF/EGFR	0.043	0.071	0.24	7	-0.33	9	16
MYC	0.003	0.1	-10000	0	-0.47	18	18
IL2	0.024	0.011	-10000	0	-10000	0	0
KU	0.038	0.011	-10000	0	-10000	0	0
RAD50	0.027	0.005	-10000	0	-10000	0	0
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
TGFB1	0.026	0.005	-10000	0	-10000	0	0
TRF2/BLM	0.042	0.026	0.22	2	-10000	0	2
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	0.083	0.11	-10000	0	-0.55	1	1
SP1/HDAC2	0.048	0.018	-10000	0	-10000	0	0
PINX1	0.023	0.01	-10000	0	-10000	0	0
Telomerase/EST1A	0.074	0.1	-10000	0	-0.54	1	1
Smad3/Myc	0.01	0.065	-10000	0	-0.28	18	18
911 complex	0.048	0.026	-10000	0	-10000	0	0
IFNG	0.068	0.082	0.23	81	-10000	0	81
Telomerase/PinX1	0.066	0.1	-10000	0	-0.52	1	1
Telomerase/AKT1/mTOR/p70S6K	0.032	0.072	-10000	0	-0.31	2	2
SIN3B	0.028	0.003	-10000	0	-10000	0	0
YWHAE	0.025	0.008	-10000	0	-10000	0	0
Telomerase/EST1B	0.072	0.096	-10000	0	-0.54	1	1
response to DNA damage stimulus	0.001	0.024	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.059	0.036	-10000	0	-10000	0	0
TRF2/WRN	0.033	0.018	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	0.078	0.098	-10000	0	-0.52	1	1
E2F1	0.081	0.095	0.24	97	-10000	0	97
ZNFX1	0.026	0.008	-10000	0	-10000	0	0
PIF1	0.041	0.057	0.21	33	-0.47	1	34
NCL	0.026	0.008	-10000	0	-10000	0	0
DKC1	0.027	0.004	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.028	0.002	-10000	0	-10000	0	0
HDAC3	0.027	0.005	-10000	0	-10000	0	0
VDR	0.026	0.038	0.33	1	-0.47	2	3
Cbp/p300/PCAF	0.047	0.026	-10000	0	-0.28	1	1
EP300	0.027	0.006	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.011	0.069	-10000	0	-0.31	7	7
KAT2B	0.025	0.025	-10000	0	-0.47	1	1
MAPK14	0.027	0.003	-10000	0	-10000	0	0
AKT1	0.011	0.086	0.21	17	-0.24	24	41
RAR alpha/9cRA/Cyclin H	0.047	0.064	-10000	0	-0.28	4	4
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.007	0.078	-10000	0	-0.31	10	10
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.029	0.049	-10000	0	-0.42	3	3
NCOR2	0.027	0.004	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.018	0.025	-10000	0	-0.33	2	2
RXRs/RARs/NRIP1/9cRA	0.01	0.1	0.39	1	-0.44	5	6
NCOA2	0	0.11	-10000	0	-0.47	20	20
NCOA3	0.025	0.008	-10000	0	-10000	0	0
NCOA1	0.027	0.006	-10000	0	-10000	0	0
VDR/VDR/DNA	0.026	0.038	0.33	1	-0.47	2	3
RARG	0.028	0.004	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.037	0.006	-10000	0	-10000	0	0
MAPK3	0.027	0.006	-10000	0	-10000	0	0
MAPK1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	0.024	0.043	-10000	0	-0.47	3	3
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.014	0.082	0.29	1	-0.41	4	5
RARA	0.016	0.037	0.2	2	-0.24	6	8
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.005	0.098	-10000	0	-0.37	14	14
PRKCA	0.024	0.049	-10000	0	-0.46	4	4
RXRs/RARs/NRIP1/9cRA/HDAC1	0.005	0.1	0.3	2	-0.48	4	6
RXRG	-0.052	0.13	0.24	2	-0.3	89	91
RXRA	0.025	0.049	-10000	0	-0.22	7	7
RXRB	0.02	0.038	0.24	2	-0.27	5	7
VDR/Vit D3/DNA	0.018	0.025	-10000	0	-0.33	2	2
RBP1	0	0.12	0.21	3	-0.47	23	26
CRBP1/9-cic-RA	0	0.083	0.15	3	-0.33	23	26
RARB	-0.014	0.14	-10000	0	-0.47	34	34
PRKCG	0.03	0.038	0.23	13	-10000	0	13
MNAT1	0.027	0.005	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.004	0.094	0.3	1	-0.52	4	5
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.015	0.094	0.26	1	-0.42	5	6
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.086	0.27	5	-0.35	6	11
RXRs/RARs/NRIP1/9cRA/HDAC3	0.004	0.1	0.3	2	-0.45	5	7
positive regulation of DNA binding	0.034	0.056	-10000	0	-0.27	4	4
NRIP1	0.006	0.1	-10000	0	-10000	0	0
RXRs/RARs	0.001	0.11	0.27	1	-0.44	7	8
RXRs/RXRs/DNA/9cRA	-0.005	0.07	-10000	0	-0.42	4	4
PRKACA	0.027	0.003	-10000	0	-10000	0	0
CDK7	0.026	0.007	-10000	0	-10000	0	0
TFIIH	0.052	0.016	-10000	0	-10000	0	0
RAR alpha/9cRA	0.06	0.045	-10000	0	-0.27	1	1
CCNH	0.027	0.005	-10000	0	-10000	0	0
CREBBP	0.026	0.007	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.05	0.018	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.019	0.058	0.24	4	-0.29	2	6
adherens junction organization	0.019	0.07	0.23	2	-0.25	13	15
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.032	0.074	0.26	6	-0.33	2	8
FMN1	0.016	0.066	-10000	0	-0.25	14	14
mol:IP3	0.013	0.045	-10000	0	-0.28	2	2
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.02	0.071	-10000	0	-0.26	14	14
CTNNB1	0.027	0.006	-10000	0	-10000	0	0
AKT1	0.024	0.058	0.19	3	-0.38	1	4
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.022	0.095	0.27	1	-0.36	14	15
CTNND1	0.028	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.014	0.063	-10000	0	-0.25	13	13
VASP	0.017	0.066	-10000	0	-0.25	13	13
ZYX	0.016	0.068	-10000	0	-0.26	14	14
JUB	0.017	0.067	-10000	0	-0.25	14	14
EGFR(dimer)	0.029	0.086	0.29	1	-0.41	3	4
E-cadherin/beta catenin-gamma catenin	0.036	0.065	-10000	0	-0.29	14	14
mol:PI-3-4-5-P3	0.04	0.067	-10000	0	-0.31	2	2
PIK3CA	0.027	0.008	-10000	0	-10000	0	0
PI3K	0.041	0.069	-10000	0	-0.32	2	2
FYN	0.011	0.063	0.26	4	-0.28	4	8
mol:Ca2+	0.013	0.044	-10000	0	-0.27	2	2
JUP	0.025	0.035	-10000	0	-0.46	2	2
PIK3R1	0.026	0.026	-10000	0	-0.47	1	1
mol:DAG	0.013	0.045	-10000	0	-0.28	2	2
CDH1	0.01	0.087	-10000	0	-0.47	13	13
RhoA/GDP	0.034	0.073	0.27	5	-0.33	2	7
establishment of polarity of embryonic epithelium	0.017	0.066	-10000	0	-0.25	13	13
SRC	0.026	0.007	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
RHOA	0.026	0.006	-10000	0	-10000	0	0
EGFR	0.021	0.085	0.33	8	-0.47	9	17
CASR	0.013	0.055	0.26	5	-0.32	1	6
RhoA/GTP	0.029	0.051	-10000	0	-0.31	1	1
AKT2	0.022	0.057	0.19	2	-0.38	1	3
actin cable formation	0.016	0.066	0.19	5	-0.25	13	18
apoptosis	-0.029	0.067	0.3	2	-0.26	5	7
CTNNA1	0.028	0.006	-10000	0	-10000	0	0
mol:GDP	0.014	0.065	0.21	9	-0.35	2	11
PIP5K1A	0.014	0.064	-10000	0	-0.25	13	13
PLCG1	0.013	0.045	-10000	0	-0.28	2	2
Rac1/GTP	0.036	0.082	0.27	1	-0.45	2	3
homophilic cell adhesion	0.001	0.003	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.028	0.014	0.21	2	-10000	0	2
Rac1/GDP	0.024	0.012	-10000	0	-10000	0	0
DOCK1	0.024	0.035	-10000	0	-0.47	2	2
ITGA4	0.013	0.085	0.21	1	-0.47	12	13
RAC1	0.026	0.006	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.024	0.076	-10000	0	-0.33	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.008	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.041	0.06	-10000	0	-0.28	12	12
alpha4/beta7 Integrin/Paxillin	0.032	0.062	-10000	0	-0.26	17	17
lamellipodium assembly	0.009	0.077	-10000	0	-0.36	8	8
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
PI3K	0.035	0.023	-10000	0	-0.34	1	1
ARF6	0.027	0.005	-10000	0	-10000	0	0
TLN1	0.025	0.009	-10000	0	-10000	0	0
PXN	0.015	0.003	-10000	0	-10000	0	0
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
ARF6/GTP	0.043	0.053	-10000	0	-0.22	12	12
cell adhesion	0.042	0.053	-10000	0	-0.24	11	11
CRKL/CBL	0.038	0.015	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.034	0.054	-10000	0	-0.26	12	12
ITGB1	0.026	0.006	-10000	0	-10000	0	0
ITGB7	0.021	0.055	-10000	0	-0.47	5	5
ARF6/GDP	0.025	0.011	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.037	0.089	-10000	0	-0.3	23	23
p130Cas/Crk/Dock1	0.045	0.032	-10000	0	-0.28	2	2
VCAM1	0.008	0.1	0.21	2	-0.47	17	19
alpha4/beta1 Integrin/Paxillin/Talin	0.043	0.054	-10000	0	-0.24	11	11
alpha4/beta1 Integrin/Paxillin/GIT1	0.045	0.056	-10000	0	-0.24	12	12
BCAR1	0.026	0.006	-10000	0	-10000	0	0
mol:GDP	-0.043	0.055	0.24	12	-10000	0	12
CBL	0.026	0.007	-10000	0	-10000	0	0
PRKACA	0.027	0.003	-10000	0	-10000	0	0
GIT1	0.026	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.043	0.054	-10000	0	-0.24	11	11
Rac1/GTP	0.008	0.083	-10000	0	-0.4	8	8

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.12	0.13	-10000	0	-0.37	30	30
CaM/Ca2+	0.02	0.003	-10000	0	-10000	0	0
AKT1	0.027	0.005	-10000	0	-10000	0	0
AKT2	0.027	0.006	-10000	0	-10000	0	0
STXBP4	0.026	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.13	0.13	-10000	0	-0.39	35	35
YWHAZ	0.021	0.012	-10000	0	-10000	0	0
CALM1	0.027	0.005	-10000	0	-10000	0	0
YWHAQ	0.026	0.006	-10000	0	-10000	0	0
TBC1D4	0.014	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.027	0.006	-10000	0	-10000	0	0
YWHAB	0.025	0.008	-10000	0	-10000	0	0
SNARE/Synip	0.048	0.02	-10000	0	-10000	0	0
YWHAG	0.027	0.004	-10000	0	-10000	0	0
ASIP	0.013	0.031	0.24	4	-10000	0	4
PRKCI	0.026	0.007	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.02	0.003	-10000	0	-10000	0	0
RHOQ	0.027	0.005	-10000	0	-10000	0	0
GYS1	0.014	0.017	0.25	2	-10000	0	2
PRKCZ	0.024	0.043	-10000	0	-0.47	3	3
TRIP10	0.026	0.025	-10000	0	-0.47	1	1
TC10/GTP/CIP4/Exocyst	0.035	0.017	-10000	0	-0.26	1	1
AS160/14-3-3	0.032	0.054	0.22	2	-0.35	1	3
VAMP2	0.025	0.008	-10000	0	-10000	0	0
SLC2A4	-0.14	0.14	-10000	0	-0.43	36	36
STX4	0.027	0.005	-10000	0	-10000	0	0
GSK3B	0.021	0.008	-10000	0	-10000	0	0
SFN	0.038	0.066	0.21	32	-0.47	3	35
LNPEP	0.027	0.005	-10000	0	-10000	0	0
YWHAE	0.025	0.008	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0.029	0.11	-10000	0	-0.66	3	3
oxygen homeostasis	0.006	0.011	-10000	0	-10000	0	0
TCEB2	0.027	0.011	0.21	1	-10000	0	1
TCEB1	0.024	0.009	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.056	0.084	-10000	0	-0.26	3	3
EPO	0.096	0.15	0.43	2	-0.45	3	5
FIH (dimer)	0.031	0.018	-10000	0	-10000	0	0
APEX1	0.027	0.027	-10000	0	-10000	0	0
SERPINE1	0.085	0.16	0.42	1	-0.55	6	7
FLT1	0.027	0.12	-10000	0	-0.59	8	8
ADORA2A	0.089	0.15	0.4	5	-0.48	3	8
germ cell development	0.098	0.16	0.48	5	-0.46	5	10
SLC11A2	0.086	0.15	0.42	1	-0.49	2	3
BHLHE40	0.078	0.15	0.42	1	-0.5	5	6
HIF1AN	0.031	0.018	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.077	0.11	0.37	1	-0.3	1	2
ETS1	0.036	0.013	-10000	0	-10000	0	0
CITED2	0.031	0.098	-10000	0	-0.57	7	7
KDR	0.022	0.14	-10000	0	-0.7	10	10
PGK1	0.087	0.15	0.42	1	-0.5	3	4
SIRT1	0.027	0.005	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	0.12	0.18	-10000	0	-0.56	3	3
EPAS1	0.04	0.079	-10000	0	-0.26	6	6
SP1	0.033	0.005	-10000	0	-10000	0	0
ABCG2	0.079	0.17	0.42	2	-0.47	12	14
EFNA1	0.088	0.15	0.46	4	-0.5	3	7
FXN	0.089	0.14	0.39	2	-0.48	3	5
POU5F1	0.097	0.16	0.48	4	-0.47	5	9
neuron apoptosis	-0.12	0.18	0.55	3	-10000	0	3
EP300	0.027	0.006	-10000	0	-10000	0	0
EGLN3	0.021	0.071	-10000	0	-0.46	8	8
EGLN2	0.03	0.018	-10000	0	-10000	0	0
EGLN1	0.031	0.018	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.043	0.025	-10000	0	-10000	0	0
VHL	0.025	0.009	-10000	0	-10000	0	0
ARNT	0.025	0.025	-10000	0	-10000	0	0
SLC2A1	0.088	0.15	0.4	5	-0.48	3	8
TWIST1	0.042	0.23	0.38	4	-0.45	56	60
ELK1	0.033	0.004	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.078	0.11	-10000	0	-10000	0	0
VEGFA	0.086	0.15	0.42	1	-0.5	3	4
CREBBP	0.026	0.007	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.034	0.01	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	0.015	0.004	-10000	0	-10000	0	0
mol:DAG	0.021	0.027	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.03	0.01	-10000	0	-10000	0	0
CaM/Ca2+	0.035	0.027	-10000	0	-10000	0	0
HIF1A	0.034	0.011	0.22	1	-10000	0	1
GAB1	0.026	0.006	-10000	0	-10000	0	0
AKT1	0.026	0.045	-10000	0	-10000	0	0
PLCG1	0.021	0.028	-10000	0	-10000	0	0
NOS3	0.036	0.05	0.29	2	-0.34	1	3
CBL	0.026	0.007	-10000	0	-10000	0	0
mol:NO	0.037	0.053	0.3	3	-0.33	1	4
FLT1	0.02	0.006	-10000	0	-10000	0	0
PGF	0.033	0.033	0.21	13	-10000	0	13
VEGFR1 homodimer/NRP2/VEGFR121	0.032	0.065	-10000	0	-0.26	18	18
CALM1	0.027	0.005	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
eNOS/Hsp90	0.049	0.054	0.29	2	-0.32	1	3
endothelial cell proliferation	-0.022	0.11	0.31	6	-0.36	3	9
mol:Ca2+	0.021	0.027	-10000	0	-10000	0	0
MAPK3	-0.002	0.037	-10000	0	-10000	0	0
MAPK1	-0.002	0.038	-10000	0	-10000	0	0
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
PLGF homodimer	0.033	0.033	0.21	13	-10000	0	13
PRKACA	0.027	0.003	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.005	0.1	-10000	0	-0.47	18	18
VEGFA homodimer	0.027	0.005	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.033	0.011	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	0.006	0.054	0.34	1	-10000	0	1
PI3K	0.058	0.037	-10000	0	-0.24	1	1
PRKCA	0.007	0.037	0.19	7	-0.24	4	11
PRKCB	-0.053	0.11	0.19	5	-0.24	98	103
VEGFR1 homodimer/PLGF homodimer	0.038	0.025	-10000	0	-10000	0	0
VEGFA	0.027	0.005	-10000	0	-10000	0	0
VEGFB	0.027	0.003	-10000	0	-10000	0	0
mol:IP3	0.021	0.027	-10000	0	-10000	0	0
RASA1	0.021	0.029	-10000	0	-10000	0	0
NRP2	0.005	0.1	-10000	0	-0.47	18	18
VEGFR1 homodimer	0.02	0.006	-10000	0	-10000	0	0
VEGFB homodimer	0.027	0.003	-10000	0	-10000	0	0
NCK1	0.026	0.006	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.04	0.069	0.3	2	-0.32	1	3
PTPN11	0.027	0.005	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.056	0.036	-10000	0	-0.24	1	1
mol:L-citrulline	0.037	0.053	0.3	3	-0.33	1	4
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.057	0.024	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.045	0.018	-10000	0	-10000	0	0
CD2AP	0.027	0.003	-10000	0	-10000	0	0
PI3K/GAB1	0.069	0.044	-10000	0	-0.23	1	1
PDPK1	0.028	0.048	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.045	0.018	-10000	0	-10000	0	0
mol:NADP	0.037	0.053	0.3	3	-0.33	1	4
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.055	0.024	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2	0.019	0.066	-10000	0	-0.28	18	18

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.061	0.044	-10000	0	-0.26	6	6
HDAC3	0.027	0.005	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0.007	0.003	-10000	0	-10000	0	0
GATA1/HDAC4	0.035	0.012	-10000	0	-10000	0	0
GATA1/HDAC5	0.037	0.008	-10000	0	-10000	0	0
GATA2/HDAC5	0.037	0.052	0.24	1	-0.34	6	7
HDAC5/BCL6/BCoR	0.051	0.017	-10000	0	-10000	0	0
HDAC9	-0.005	0.12	-10000	0	-0.47	25	25
Glucocorticoid receptor/Hsp90/HDAC6	0.043	0.057	-10000	0	-0.28	11	11
HDAC4/ANKRA2	0.036	0.014	-10000	0	-10000	0	0
HDAC5/YWHAB	0.037	0.013	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.015	0.005	-10000	0	-10000	0	0
GATA2	0.025	0.07	0.22	13	-0.47	6	19
HDAC4/RFXANK	0.038	0.014	-10000	0	-10000	0	0
BCOR	0.027	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.026	0.006	-10000	0	-10000	0	0
HDAC5	0.027	0.005	-10000	0	-10000	0	0
GNB1/GNG2	0.034	0.046	-10000	0	-0.34	6	6
Histones	0.006	0.069	-10000	0	-0.26	6	6
ADRBK1	0.027	0.005	-10000	0	-10000	0	0
HDAC4	0.025	0.008	-10000	0	-10000	0	0
XPO1	0.027	0.005	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.038	0.011	-10000	0	-10000	0	0
HDAC4/Ubc9	0.037	0.013	-10000	0	-10000	0	0
HDAC7	0.027	0.004	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.036	0.013	-10000	0	-10000	0	0
TUBA1B	0.027	0.003	-10000	0	-10000	0	0
HDAC6	0.027	0.003	-10000	0	-10000	0	0
HDAC5/RFXANK	0.04	0.011	-10000	0	-10000	0	0
CAMK4	0.016	0.07	0.21	1	-0.47	8	9
Tubulin/HDAC6	0.05	0.028	-10000	0	-0.28	2	2
SUMO1	0.027	0.005	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.025	0.008	-10000	0	-10000	0	0
GATA1	0.014	0.021	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.025	0.008	-10000	0	-10000	0	0
NR3C1	0.013	0.081	-10000	0	-0.47	11	11
SUMO1/HDAC4	0.033	0.044	-10000	0	-0.21	5	5
SRF	0.027	0.005	-10000	0	-10000	0	0
HDAC4/YWHAB	0.034	0.015	-10000	0	-10000	0	0
Tubulin	0.036	0.028	-10000	0	-0.34	2	2
HDAC4/14-3-3 E	0.035	0.015	-10000	0	-10000	0	0
GNB1	0.027	0.003	-10000	0	-10000	0	0
RANGAP1	0.027	0.005	-10000	0	-10000	0	0
BCL6/BCoR	0.038	0.011	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.049	0.019	-10000	0	-10000	0	0
HDAC4/SRF	0.041	0.051	-10000	0	-0.28	8	8
HDAC4/ER alpha	-0.024	0.14	-10000	0	-0.33	66	66
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.006	0.068	-10000	0	-0.26	6	6
cell motility	0.05	0.028	-10000	0	-0.28	2	2
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.027	0.006	-10000	0	-10000	0	0
HDAC7/HDAC3	0.039	0.009	-10000	0	-10000	0	0
BCL6	0.026	0.006	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.025	0.008	-10000	0	-10000	0	0
Hsp90/HDAC6	0.039	0.009	-10000	0	-10000	0	0
ESR1	-0.054	0.18	-10000	0	-0.47	66	66
HDAC6/HDAC11	0.034	0.036	0.24	1	-0.34	3	4
Ran/GTP/Exportin 1	0.033	0.046	-10000	0	-0.28	2	2
NPC	0.016	0.003	-10000	0	-10000	0	0
MEF2C	0.013	0.081	-10000	0	-0.47	11	11
RAN	0.027	0.005	-10000	0	-10000	0	0
HDAC4/MEF2C	0.061	0.058	-10000	0	-0.24	10	10
GNG2	0.02	0.06	-10000	0	-0.47	6	6
NCOR2	0.027	0.004	-10000	0	-10000	0	0
TUBB2A	0.024	0.035	-10000	0	-0.47	2	2
HDAC11	0.022	0.046	0.33	1	-0.47	3	4
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
RANBP2	0.027	0.004	-10000	0	-10000	0	0
ANKRA2	0.026	0.006	-10000	0	-10000	0	0
RFXANK	0.028	0.01	0.21	1	-10000	0	1
nuclear import	-0.028	0.019	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.027	0.011	0.21	1	-9999	1
PLK4	0.032	0.029	0.21	10	-9999	10
regulation of centriole replication	0.015	0.007	-10000	0	-9999	0

×

TRAIL 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
TNFSF10	0.035	0.043	0.23	17	-10000	0	17
positive regulation of NF-kappaB transcription factor activity	0.032	0.046	0.24	1	-0.34	4	5
MAP2K4	0.027	0.042	0.26	2	-10000	0	2
IKBKB	0.025	0.009	-10000	0	-10000	0	0
TNFRSF10B	0.023	0.011	-10000	0	-10000	0	0
TNFRSF10A	0.022	0.027	-10000	0	-0.47	1	1
SMPD1	0.013	0.01	0.15	1	-10000	0	1
IKBKG	0.027	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.017	0.055	-10000	0	-0.47	5	5
TRAIL/TRAILR2	0.036	0.028	0.24	1	-10000	0	1
TRAIL/TRAILR3	0.036	0.037	0.24	1	-0.34	1	2
TRAIL/TRAILR1	0.035	0.034	0.24	1	-0.34	1	2
TRAIL/TRAILR4	0.032	0.046	0.24	1	-0.34	4	5
TRAIL/TRAILR1/DAP3/GTP	0.042	0.032	0.22	1	-10000	0	1
IKK complex	0.017	0.046	-10000	0	-10000	0	0
RIPK1	0.026	0.007	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.019	0.005	-10000	0	-10000	0	0
MAPK3	0.017	0.025	0.3	3	-10000	0	3
MAP3K1	0.027	0.039	0.28	1	-10000	0	1
TRAILR4 (trimer)	0.017	0.055	-10000	0	-0.47	5	5
TRADD	0.027	0.006	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.022	0.026	-10000	0	-0.47	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.022	0.028	-10000	0	-0.22	1	1
CFLAR	0.027	0.006	-10000	0	-10000	0	0
MAPK1	0.017	0.025	0.3	3	-10000	0	3
TRAIL/TRAILR1/FADD/TRADD/RIP	0.059	0.05	-10000	0	-0.24	1	1
mol:ceramide	0.013	0.01	0.15	1	-10000	0	1
FADD	0.03	0.037	0.33	6	-10000	0	6
MAPK8	0.023	0.057	0.26	4	-10000	0	4
TRAF2	0.025	0.009	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.024	0.034	0.21	5	-0.47	1	6
CHUK	0.027	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.046	0.042	0.24	6	-0.28	1	7
DAP3	0.026	0.007	-10000	0	-10000	0	0
CASP10	0.028	0.06	0.25	12	-10000	0	12
JNK cascade	0.032	0.046	0.24	1	-0.34	4	5
TRAIL (trimer)	0.035	0.043	0.23	17	-10000	0	17
TNFRSF10C	0.024	0.034	0.21	5	-0.47	1	6
TRAIL/TRAILR1/DAP3/GTP/FADD	0.05	0.042	0.22	6	-10000	0	6
TRAIL/TRAILR2/FADD	0.046	0.039	0.24	6	-10000	0	6
cell death	0.013	0.01	0.15	1	-10000	0	1
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.023	0.026	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.023	0.011	-10000	0	-10000	0	0
CASP8	-0.017	0.13	-10000	0	-0.56	20	20
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.06	0.048	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.015	0.056	-10000	0	-10000	0	0
PLK1	0.1	0.12	0.53	2	-10000	0	2
CDKN1B	0.11	0.099	0.37	4	-0.34	4	8
FOXO3	0.097	0.11	0.39	1	-10000	0	1
KAT2B	0.036	0.032	-10000	0	-0.46	1	1
FOXO1/SIRT1	0.025	0.049	0.27	1	-0.23	1	2
CAT	0.094	0.11	0.48	1	-10000	0	1
CTNNB1	0.027	0.006	-10000	0	-10000	0	0
AKT1	0.04	0.02	-10000	0	-10000	0	0
FOXO1	0.015	0.053	0.35	1	-0.26	1	2
MAPK10	0.013	0.079	0.2	13	-0.23	33	46
mol:GTP	0.002	0	-10000	0	-10000	0	0
FOXO4	0.056	0.065	0.3	1	-10000	0	1
response to oxidative stress	0.016	0.012	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.11	0.089	0.41	1	-10000	0	1
XPO1	0.027	0.005	-10000	0	-10000	0	0
EP300	0.029	0.007	-10000	0	-10000	0	0
BCL2L11	0.037	0.091	-10000	0	-0.72	5	5
FOXO1/SKP2	0.027	0.056	0.28	4	-0.26	1	5
mol:GDP	0.016	0.012	-10000	0	-10000	0	0
RAN	0.028	0.005	-10000	0	-10000	0	0
GADD45A	0.1	0.08	-10000	0	-0.43	1	1
YWHAQ	0.026	0.006	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.05	0.099	-10000	0	-0.55	5	5
MST1	0.047	0.055	0.24	21	-0.45	1	22
CSNK1D	0.027	0.006	-10000	0	-10000	0	0
CSNK1E	0.027	0.006	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.04	0.084	-10000	0	-0.47	4	4
YWHAB	0.025	0.008	-10000	0	-10000	0	0
MAPK8	0.034	0.041	0.2	14	-0.23	3	17
MAPK9	0.034	0.033	0.2	14	-10000	0	14
YWHAG	0.027	0.004	-10000	0	-10000	0	0
YWHAE	0.025	0.008	-10000	0	-10000	0	0
YWHAZ	0.021	0.012	-10000	0	-10000	0	0
SIRT1	0.026	0.017	-10000	0	-10000	0	0
SOD2	0.1	0.097	0.49	1	-0.47	2	3
RBL2	0.085	0.14	-10000	0	-0.61	10	10
RAL/GDP	0.05	0.018	0.24	1	-10000	0	1
CHUK	0.038	0.019	-10000	0	-10000	0	0
Ran/GTP	0.023	0.004	-10000	0	-10000	0	0
CSNK1G2	0.027	0.005	-10000	0	-10000	0	0
RAL/GTP	0.053	0.017	0.23	1	-10000	0	1
CSNK1G1	0.027	0.004	-10000	0	-10000	0	0
FASLG	-0.018	0.3	-10000	0	-1.3	20	20
SKP2	0.029	0.038	0.26	9	-10000	0	9
USP7	0.027	0.007	-10000	0	-10000	0	0
IKBKB	0.035	0.021	-10000	0	-10000	0	0
CCNB1	0.098	0.11	-10000	0	-10000	0	0
FOXO1-3a-4/beta catenin	0.11	0.093	0.35	5	-10000	0	5
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.056	0.28	4	-0.26	1	5
CSNK1A1	0.027	0.006	-10000	0	-10000	0	0
SGK1	0.017	0.098	-10000	0	-0.46	16	16
CSNK1G3	0.027	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.04	0.011	-10000	0	-10000	0	0
ZFAND5	0.055	0.061	-10000	0	-10000	0	0
SFN	0.038	0.066	0.21	32	-0.47	3	35
CDK2	0.028	0.006	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.055	0.077	-10000	0	-0.5	2	2
CREBBP	0.027	0.008	-10000	0	-10000	0	0
FBXO32	0.11	0.15	0.5	8	-1.1	1	9
BCL6	0.1	0.089	-10000	0	-10000	0	0
RALB	0.028	0.004	-10000	0	-10000	0	0
RALA	0.029	0.016	0.33	1	-10000	0	1
YWHAH	0.027	0.006	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.003	0.12	-10000	0	-0.34	44	44
AKT1	0.048	0.078	0.32	3	-0.43	2	5
PTK2B	0.004	0.09	0.35	1	-0.33	4	5
VEGFR2 homodimer/Frs2	0.036	0.038	-10000	0	-0.34	1	1
CAV1	0.005	0.1	-10000	0	-0.47	18	18
CALM1	0.027	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.049	0.039	-10000	0	-10000	0	0
endothelial cell proliferation	0.024	0.12	0.34	9	-0.36	5	14
mol:Ca2+	0.027	0.046	-10000	0	-0.26	2	2
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.06	0.033	-10000	0	-10000	0	0
RP11-342D11.1	0.017	0.044	-10000	0	-0.25	2	2
CDH5	0.024	0.035	-10000	0	-0.47	2	2
VEGFA homodimer	0.054	0.032	-10000	0	-10000	0	0
SHC1	0.026	0.017	0.33	1	-10000	0	1
SHC2	-0.002	0.12	0.21	1	-0.47	24	25
HRAS/GDP	0.039	0.033	-10000	0	-10000	0	0
SH2D2A	0.028	0.023	0.24	4	-10000	0	4
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.062	0.072	-10000	0	-0.44	2	2
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.049	0.03	-10000	0	-10000	0	0
VEGFR1 homodimer	0.027	0.005	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.072	0.045	-10000	0	-10000	0	0
GRB10	0.023	0.065	-10000	0	-0.47	5	5
PTPN11	0.027	0.005	-10000	0	-10000	0	0
GRB2	0.027	0.005	-10000	0	-10000	0	0
PAK1	0.025	0.025	-10000	0	-0.47	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.071	0.049	-10000	0	-0.37	2	2
HRAS	0.025	0.008	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.007	0.077	-10000	0	-0.33	6	6
HIF1A	0.027	0.01	0.21	1	-10000	0	1
FRS2	0.031	0.04	0.33	7	-10000	0	7
oxygen and reactive oxygen species metabolic process	0.058	0.033	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.025	0.025	-10000	0	-0.47	1	1
Nck/Pak	0.037	0.022	-10000	0	-0.34	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.045	0.039	-10000	0	-0.25	3	3
mol:GDP	0.055	0.037	-10000	0	-10000	0	0
mol:NADP	0.05	0.077	0.33	2	-0.42	2	4
eNOS/Hsp90	0.061	0.075	0.32	2	-0.4	2	4
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
mol:IP3	0.027	0.047	-10000	0	-0.26	2	2
HIF1A/ARNT	0.035	0.015	-10000	0	-10000	0	0
SHB	0.024	0.009	-10000	0	-10000	0	0
VEGFA	0.027	0.012	-10000	0	-10000	0	0
VEGFC	0.024	0.036	0.21	1	-0.47	2	3
FAK1/Vinculin	0.028	0.098	0.31	2	-0.44	2	4
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.026	0.006	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.03	0.096	-10000	0	-0.35	4	4
PTPN6	0.027	0.011	0.21	1	-10000	0	1
EPAS1	0.034	0.009	-10000	0	-10000	0	0
mol:L-citrulline	0.05	0.077	0.33	2	-0.42	2	4
ITGAV	0.027	0.006	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.06	0.043	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer	0.051	0.042	-10000	0	-0.26	5	5
VEGFR2/3 heterodimer	0.032	0.036	-10000	0	-0.58	1	1
VEGFB	0.027	0.003	-10000	0	-10000	0	0
MAPK11	0.022	0.058	0.32	2	-10000	0	2
VEGFR2 homodimer	0.022	0.023	-10000	0	-0.4	1	1
FLT1	0.027	0.005	-10000	0	-10000	0	0
NEDD4	0.026	0.027	-10000	0	-0.46	1	1
MAPK3	0	0.086	0.26	7	-0.31	4	11
MAPK1	0.002	0.087	0.25	10	-0.31	4	14
VEGFA145/NRP2	0.022	0.078	-10000	0	-0.34	18	18
VEGFR1/2 heterodimer	0.034	0.026	-10000	0	-0.34	1	1
KDR	0.022	0.023	-10000	0	-0.4	1	1
VEGFA165/NRP1/VEGFR2 homodimer	0.038	0.071	-10000	0	-0.31	3	3
SRC	0.026	0.007	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	0.009	0.09	0.27	8	-0.31	4	12
PI3K	0.043	0.054	-10000	0	-0.51	1	1
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.048	0.027	-10000	0	-10000	0	0
FES	0.028	0.045	-10000	0	-0.26	2	2
GAB1	0.043	0.044	-10000	0	-0.34	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	0.046	0.03	-10000	0	-10000	0	0
CTNNB1	0.027	0.006	-10000	0	-10000	0	0
SOS1	0.027	0.005	-10000	0	-10000	0	0
ARNT	0.024	0.01	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.052	0.08	0.3	1	-0.4	2	3
VEGFR2 homodimer/VEGFA homodimer/Yes	0.045	0.03	-10000	0	-10000	0	0
PI3K/GAB1	0.047	0.07	-10000	0	-0.44	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.07	0.05	-10000	0	-10000	0	0
PRKACA	0.027	0.003	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.044	0.041	-10000	0	-0.39	2	2
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
CDC42	0.029	0.046	-10000	0	-0.26	2	2
actin cytoskeleton reorganization	0.048	0.029	-10000	0	-10000	0	0
PTK2	0.009	0.081	-10000	0	-0.41	3	3
EDG1	0.017	0.044	-10000	0	-0.25	2	2
mol:DAG	0.027	0.047	-10000	0	-0.26	2	2
CaM/Ca2+	0.042	0.049	-10000	0	-10000	0	0
MAP2K3	0.023	0.052	0.37	1	-10000	0	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.049	0.069	-10000	0	-0.48	5	5
PLCG1	0.027	0.047	-10000	0	-0.26	2	2
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.052	0.038	-10000	0	-10000	0	0
IQGAP1	0.027	0.004	-10000	0	-10000	0	0
YES1	0.025	0.008	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.048	0.029	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.05	0.027	0.29	1	-10000	0	1
cell migration	0.035	0.094	0.32	3	-0.43	2	5
mol:PI-3-4-5-P3	0.042	0.052	-10000	0	-0.47	1	1
FYN	0.022	0.043	-10000	0	-0.47	3	3
VEGFB/NRP1	0.032	0.044	-10000	0	-0.24	2	2
mol:NO	0.05	0.077	0.33	2	-0.42	2	4
PXN	0.027	0.004	-10000	0	-10000	0	0
HRAS/GTP	0.023	0.025	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.039	0.063	-10000	0	-0.48	5	5
VHL	0.025	0.009	-10000	0	-10000	0	0
ITGB3	-0.027	0.15	-10000	0	-0.47	44	44
NOS3	0.051	0.082	0.34	2	-0.48	2	4
VEGFR2 homodimer/VEGFA homodimer/Sck	0.032	0.076	-10000	0	-0.26	22	22
RAC1	0.026	0.006	-10000	0	-10000	0	0
PRKCA	0.02	0.062	0.37	1	-0.44	1	2
PRKCB	-0.039	0.12	-10000	0	-0.43	4	4
VCL	0.027	0.006	-10000	0	-10000	0	0
VEGFA165/NRP1	0.036	0.045	-10000	0	-0.25	2	2
VEGFR1/2 heterodimer/VEGFA homodimer	0.049	0.028	-10000	0	-10000	0	0
VEGFA165/NRP2	0.022	0.078	-10000	0	-0.34	18	18
MAPKKK cascade	0.045	0.066	0.36	2	-0.4	3	5
NRP2	0.005	0.1	-10000	0	-0.47	18	18
VEGFC homodimer	0.024	0.036	0.21	1	-0.47	2	3
NCK1	0.026	0.006	-10000	0	-10000	0	0
ROCK1	0.027	0.006	-10000	0	-10000	0	0
FAK1/Paxillin	0.029	0.099	0.3	3	-0.44	2	5
MAP3K13	0.028	0.045	-10000	0	-10000	0	0
PDPK1	0.036	0.058	0.27	6	-0.43	1	7

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.028	0.002	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0.005	0.01	-10000	0	-10000	0	0
MDM2/SUMO1	0.036	0.058	0.22	12	-0.21	6	18
HDAC4	0.025	0.008	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0.005	0.011	-10000	0	-10000	0	0
SUMO1	0.027	0.005	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1	0.01	0.026	-10000	0	-0.2	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	0.01	0.022	-10000	0	-0.22	3	3
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.027	0.005	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.027	0.004	-10000	0	-10000	0	0
SUMO1/HDAC4	0.033	0.044	-10000	0	-0.21	5	5
SUMO1/HDAC1	0.033	0.048	-10000	0	-0.29	2	2
RANGAP1	0.027	0.005	-10000	0	-10000	0	0
MDM2/SUMO1/SUMO1	0.066	0.04	0.24	12	-10000	0	12
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.015	0.005	-10000	0	-10000	0	0
Ran/GTP	0.021	0.043	-10000	0	-0.18	11	11
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.036	0.054	0.33	13	-10000	0	13
UBE2I	0.027	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.024	0.051	0.2	11	-0.28	2	13
NPC	0.016	0.003	-10000	0	-10000	0	0
PIAS2	0.026	0.007	-10000	0	-10000	0	0
PIAS1	0.027	0.004	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0

×

Canonical NF-kappaB 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
FBXW11	0.028	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.066	0.077	0.28	8	-0.32	2	10
ERC1	0.027	0.006	-10000	0	-10000	0	0
RIP2/NOD2	0.04	0.039	-10000	0	-0.34	1	1
NFKBIA	0.02	0.03	-10000	0	-10000	0	0
BIRC2	0.028	0.022	0.33	2	-10000	0	2
IKBKB	0.025	0.009	-10000	0	-10000	0	0
RIPK2	0.024	0.01	-10000	0	-10000	0	0
IKBKG	0.041	0.039	-10000	0	-10000	0	0
IKK complex/A20	0.068	0.081	0.3	1	-0.36	2	3
NEMO/A20/RIP2	0.023	0.01	-10000	0	-10000	0	0
XPO1	0.027	0.005	-10000	0	-10000	0	0
NEMO/ATM	0.054	0.072	0.28	2	-0.32	7	9
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.027	0.005	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.035	0.01	-10000	0	-10000	0	0
IKK complex/ELKS	0.05	0.066	-10000	0	-0.34	2	2
BCL10/MALT1/TRAF6	0.049	0.02	-10000	0	-10000	0	0
NOD2	0.035	0.057	0.21	24	-0.47	2	26
NFKB1	0.03	0.004	-10000	0	-10000	0	0
RELA	0.029	0.005	-10000	0	-10000	0	0
MALT1	0.026	0.007	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.039	0.018	0.24	2	-10000	0	2
ATM	0.026	0.007	-10000	0	-10000	0	0
TNF/TNFR1A	0.045	0.031	-10000	0	-10000	0	0
TRAF6	0.026	0.008	-10000	0	-10000	0	0
PRKCA	0.022	0.049	-10000	0	-0.47	4	4
CHUK	0.027	0.005	-10000	0	-10000	0	0
UBE2D3	0.027	0.004	-10000	0	-10000	0	0
TNF	0.036	0.042	0.21	21	-10000	0	21
NF kappa B1 p50/RelA	0.059	0.019	-10000	0	-10000	0	0
BCL10	0.027	0.004	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.03	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.028	0.007	-10000	0	-10000	0	0
TNFRSF1A	0.027	0.005	-10000	0	-10000	0	0
IKK complex	0.059	0.073	-10000	0	-0.31	5	5
CYLD	0.027	0.005	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.063	0.078	-10000	0	-0.35	2	2

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.027	0.02	-10000	0	-10000	0	0
regulation of axonogenesis	-0.011	0.026	0.24	4	-10000	0	4
myoblast fusion	-0.026	0.025	-10000	0	-10000	0	0
mol:GTP	0.018	0.027	-10000	0	-0.15	9	9
regulation of calcium-dependent cell-cell adhesion	-0.051	0.04	0.26	3	-10000	0	3
ARF1/GTP	0.034	0.026	-10000	0	-10000	0	0
mol:GM1	0.008	0.02	-10000	0	-10000	0	0
mol:Choline	0.011	0.014	-10000	0	-10000	0	0
lamellipodium assembly	0.013	0.055	-10000	0	-0.34	8	8
MAPK3	0.025	0.018	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.052	0.04	-10000	0	-0.26	3	3
ARF1	0.027	0.003	-10000	0	-10000	0	0
ARF6/GDP	0.026	0.025	-10000	0	-10000	0	0
ARF1/GDP	0.029	0.044	-10000	0	-0.23	3	3
ARF6	0.033	0.009	-10000	0	-10000	0	0
RAB11A	0.027	0.004	-10000	0	-10000	0	0
TIAM1	0.025	0.043	-10000	0	-0.47	3	3
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.025	0.017	-10000	0	-10000	0	0
actin filament bundle formation	-0.033	0.041	0.22	3	-10000	0	3
KALRN	0.014	0.022	-10000	0	-0.24	2	2
RAB11FIP3/RAB11A	0.039	0.01	-10000	0	-10000	0	0
RhoA/GDP	0.033	0.042	-10000	0	-0.22	3	3
NME1	0.029	0.011	0.21	1	-10000	0	1
Rac1/GDP	0.033	0.041	-10000	0	-0.2	9	9
substrate adhesion-dependent cell spreading	0.018	0.027	-10000	0	-0.15	9	9
cortical actin cytoskeleton organization	0.013	0.056	-10000	0	-0.34	8	8
RAC1	0.026	0.006	-10000	0	-10000	0	0
liver development	0.018	0.027	-10000	0	-0.15	9	9
ARF6/GTP	0.018	0.027	-10000	0	-0.15	9	9
RhoA/GTP	0.033	0.026	-10000	0	-10000	0	0
mol:GDP	0.012	0.033	-10000	0	-0.21	7	7
ARF6/GTP/RAB11FIP3/RAB11A	0.048	0.026	-10000	0	-10000	0	0
RHOA	0.026	0.006	-10000	0	-10000	0	0
PLD1	0.018	0.022	-10000	0	-10000	0	0
RAB11FIP3	0.027	0.005	-10000	0	-10000	0	0
tube morphogenesis	0.013	0.055	-10000	0	-0.34	8	8
ruffle organization	0.011	0.026	-10000	0	-0.24	4	4
regulation of epithelial cell migration	0.018	0.027	-10000	0	-0.15	9	9
PLD2	0.019	0.018	-10000	0	-10000	0	0
PIP5K1A	0.011	0.026	-10000	0	-0.24	4	4
mol:Phosphatidic acid	0.011	0.014	-10000	0	-10000	0	0
Rac1/GTP	0.013	0.056	-10000	0	-0.34	8	8

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.015	0.029	-10000	0	-0.31	1	1
TRAF2/ASK1	0.031	0.021	-10000	0	-0.28	1	1
ATM	0.026	0.007	-10000	0	-10000	0	0
MAP2K3	0.005	0.096	-10000	0	-0.32	20	20
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.015	0.075	0.21	3	-0.28	7	10
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.019	0.055	-10000	0	-0.47	5	5
TXN	0.007	0.004	-10000	0	-10000	0	0
CALM1	0.027	0.005	-10000	0	-10000	0	0
GADD45A	0.028	0.002	-10000	0	-10000	0	0
GADD45B	0.015	0.077	-10000	0	-0.47	10	10
MAP3K1	0.026	0.007	-10000	0	-10000	0	0
MAP3K6	0.028	0.002	-10000	0	-10000	0	0
MAP3K7	0.026	0.006	-10000	0	-10000	0	0
MAP3K4	0.027	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.038	0.021	-10000	0	-0.34	1	1
TAK1/TAB family	-0.004	0.016	-10000	0	-10000	0	0
RAC1/OSM/MEKK3	0.049	0.017	-10000	0	-10000	0	0
TRAF2	0.025	0.009	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.023	0.082	-10000	0	-0.28	12	12
TRAF6	0.007	0.002	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.046	0.062	0.22	43	-10000	0	43
CCM2	0.027	0.01	0.21	1	-10000	0	1
CaM/Ca2+/CAMKIIB	0.047	0.036	-10000	0	-10000	0	0
MAPK11	0.026	0.006	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.06	0.042	0.22	3	-0.26	1	4
OSM/MEKK3	0.039	0.012	-10000	0	-10000	0	0
TAOK1	0.013	0.017	-10000	0	-0.3	1	1
TAOK2	0.014	0.005	-10000	0	-10000	0	0
TAOK3	0.015	0.005	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.027	0.003	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.025	0.025	-10000	0	-0.47	1	1
MAP3K10	0.027	0.016	0.33	1	-10000	0	1
MAP3K3	0.026	0.006	-10000	0	-10000	0	0
TRX/ASK1	0.014	0.037	-10000	0	-0.27	1	1
GADD45/MTK1/MTK1	0.045	0.061	-10000	0	-0.26	13	13

×

Regulation of cytoplasmic and nuclear SMAD2/3 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.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.026	0.007	-10000	0	-10000	0	0
SMAD2	0.005	0.052	0.23	4	-0.23	7	11
SMAD3	0.027	0.025	-10000	0	-10000	0	0
SMAD3/SMAD4	0.041	0.035	-10000	0	-0.36	1	1
SMAD4/Ubc9/PIASy	0.05	0.018	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.043	0.058	-10000	0	-0.29	1	1
PPM1A	0.027	0.004	-10000	0	-10000	0	0
CALM1	0.027	0.005	-10000	0	-10000	0	0
SMAD2/SMAD4	0.016	0.049	0.24	1	-0.25	3	4
MAP3K1	0.026	0.007	-10000	0	-10000	0	0
TRAP-1/SMAD4	0.035	0.038	-10000	0	-0.33	4	4
MAPK3	0.027	0.006	-10000	0	-10000	0	0
MAPK1	0.027	0.005	-10000	0	-10000	0	0
NUP214	0.025	0.008	-10000	0	-10000	0	0
CTDSP1	0.026	0.007	-10000	0	-10000	0	0
CTDSP2	0.027	0.005	-10000	0	-10000	0	0
CTDSPL	0.026	0.006	-10000	0	-10000	0	0
KPNB1	0.027	0.005	-10000	0	-10000	0	0
TGFBRAP1	0.022	0.049	-10000	0	-0.47	4	4
UBE2I	0.027	0.006	-10000	0	-10000	0	0
NUP153	0.026	0.007	-10000	0	-10000	0	0
KPNA2	0.029	0.022	0.24	4	-10000	0	4
PIAS4	0.027	0.005	-10000	0	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.052	0.028	-10000	0	-10000	0	0
CLOCK	0.03	0.004	-10000	0	-10000	0	0
TIMELESS/CRY2	0.041	0.021	-10000	0	-10000	0	0
DEC1/BMAL1	0.034	0.024	-10000	0	-10000	0	0
ATR	0.026	0.006	-10000	0	-10000	0	0
NR1D1	0.024	0.013	-10000	0	-10000	0	0
ARNTL	0.028	0.008	-10000	0	-10000	0	0
TIMELESS	0.024	0.013	-10000	0	-10000	0	0
NPAS2	0.027	0.035	-10000	0	-0.46	2	2
CRY2	0.026	0.007	-10000	0	-10000	0	0
mol:CO	-0.01	0.002	-10000	0	-10000	0	0
CHEK1	0.029	0.024	0.24	5	-10000	0	5
mol:HEME	0.01	0.002	-10000	0	-10000	0	0
PER1	0.012	0.08	-10000	0	-0.47	11	11
BMAL/CLOCK/NPAS2	0.058	0.033	-10000	0	-0.28	2	2
BMAL1/CLOCK	0.032	0.041	-10000	0	-10000	0	0
S phase of mitotic cell cycle	0.052	0.028	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.053	0.028	-10000	0	-10000	0	0
mol:NADPH	0.01	0.002	-10000	0	-10000	0	0
PER1/TIMELESS	0.032	0.049	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	-0.004	0.038	0.21	10	-10000	0	10

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	0.063	0.049	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0.007	0.002	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.036	0.055	-10000	0	-10000	0	0
SUMO1	0.027	0.005	-10000	0	-10000	0	0
ZFPM1	0.027	0.006	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.015	0.005	-10000	0	-10000	0	0
FKBP3	0.027	0.005	-10000	0	-10000	0	0
Histones	0.059	0.051	-10000	0	-10000	0	0
YY1/LSF	0.024	0.054	-10000	0	-0.2	10	10
SMG5	0.026	0.007	-10000	0	-10000	0	0
RAN	0.027	0.005	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.028	0.013	-10000	0	-10000	0	0
I kappa B alpha/HDAC1	0.031	0.049	-10000	0	-10000	0	0
SAP18	0.027	0.005	-10000	0	-10000	0	0
RELA	0.029	0.026	-10000	0	-10000	0	0
HDAC1/Smad7	0.051	0.017	-10000	0	-10000	0	0
RANGAP1	0.027	0.005	-10000	0	-10000	0	0
HDAC3/TR2	0.034	0.045	-10000	0	-10000	0	0
NuRD/MBD3 Complex	0.033	0.041	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.028	0.062	-10000	0	-0.24	3	3
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.025	0.07	0.22	13	-0.47	6	19
GATA1	0.014	0.021	-10000	0	-10000	0	0
Mad/Max	0.039	0.012	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.036	0.051	-10000	0	-10000	0	0
RBBP7	0.027	0.004	-10000	0	-10000	0	0
NPC	0.016	0.003	-10000	0	-10000	0	0
RBBP4	0.028	0.002	-10000	0	-10000	0	0
MAX	0.027	0.005	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.026	0.007	-10000	0	-10000	0	0
NFKBIA	0.024	0.01	-10000	0	-10000	0	0
KAT2B	0.025	0.025	-10000	0	-0.47	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.028	0.022	-10000	0	-0.35	1	1
SIN3 complex	0.065	0.021	-10000	0	-10000	0	0
SMURF1	0.027	0.004	-10000	0	-10000	0	0
CHD3	0.025	0.008	-10000	0	-10000	0	0
SAP30	0.026	0.006	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.025	0.009	-10000	0	-10000	0	0
YY1/HDAC3	0.025	0.047	-10000	0	-0.28	1	1
YY1/HDAC2	0.024	0.052	-10000	0	-0.21	5	5
YY1/HDAC1	0.024	0.054	-10000	0	-0.22	1	1
NuRD/MBD2 Complex (MeCP1)	0.029	0.049	-10000	0	-0.34	1	1
PPARG	0.008	0.073	-10000	0	-0.26	24	24
HDAC8/hEST1B	0.051	0.016	-10000	0	-10000	0	0
UBE2I	0.027	0.006	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.007	-10000	0	-10000	0	0
TNFRSF1A	0.027	0.005	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.034	0.045	-10000	0	-10000	0	0
MBD3L2	-0.017	0.003	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.051	0.017	-10000	0	-10000	0	0
CREBBP	0.026	0.007	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.032	0.057	-10000	0	-0.31	3	3
HDAC1	0.028	0.002	-10000	0	-10000	0	0
HDAC3	0.024	0.009	-10000	0	-10000	0	0
HDAC2	0.026	0.007	-10000	0	-10000	0	0
YY1	0.019	0.016	-10000	0	-0.25	1	1
HDAC8	0.027	0.003	-10000	0	-10000	0	0
SMAD7	0.026	0.007	-10000	0	-10000	0	0
NCOR2	0.027	0.004	-10000	0	-10000	0	0
MXD1	0.027	0.011	0.21	1	-10000	0	1
STAT3	0.021	0.008	-10000	0	-10000	0	0
NFKB1	0.027	0.004	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.027	0.004	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.037	0.054	-10000	0	-10000	0	0
YY1/SAP30/HDAC1	0.038	0.053	-10000	0	-0.2	1	1
EP300	0.027	0.006	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.021	0.008	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.01	-10000	0	-10000	0	0
histone deacetylation	0.027	0.052	-10000	0	-0.27	3	3
STAT3 (dimer non-phopshorylated)/HDAC3	0.03	0.025	-10000	0	-10000	0	0
nuclear export	-0.051	0.016	-10000	0	-10000	0	0
PRKACA	0.027	0.003	-10000	0	-10000	0	0
GATAD2B	0.025	0.008	-10000	0	-10000	0	0
GATAD2A	0.027	0.004	-10000	0	-10000	0	0
GATA2/HDAC3	0.031	0.063	0.23	1	-0.26	7	8
GATA1/HDAC1	0.038	0.007	-10000	0	-10000	0	0
GATA1/HDAC3	0.032	0.046	-10000	0	-10000	0	0
CHD4	0.027	0.005	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.045	0.031	-10000	0	-10000	0	0
SIN3/HDAC complex/Mad/Max	0.029	0.045	-10000	0	-0.46	1	1
NuRD Complex	0.031	0.056	-10000	0	-0.3	1	1
positive regulation of chromatin silencing	0.057	0.049	-10000	0	-10000	0	0
SIN3B	0.028	0.003	-10000	0	-10000	0	0
MTA2	0.027	0.003	-10000	0	-10000	0	0
SIN3A	0.027	0.004	-10000	0	-10000	0	0
XPO1	0.027	0.005	-10000	0	-10000	0	0
SUMO1/HDAC1	0.033	0.048	-10000	0	-0.29	2	2
HDAC complex	0.066	0.02	-10000	0	-10000	0	0
GATA1/Fog1	0.037	0.01	-10000	0	-10000	0	0
FKBP25/HDAC1/HDAC2	0.052	0.016	-10000	0	-10000	0	0
TNF	0.036	0.042	0.21	21	-10000	0	21
negative regulation of cell growth	0.027	0.05	-10000	0	-0.29	4	4
NuRD/MBD2/PRMT5 Complex	0.029	0.049	-10000	0	-0.34	1	1
Ran/GTP/Exportin 1	0.033	0.046	-10000	0	-0.28	2	2
NF kappa B/RelA/I kappa B alpha	0.023	0.039	-10000	0	-10000	0	0
SIN3/HDAC complex/NCoR1	0.016	0.054	-10000	0	-0.29	5	5
TFCP2	0.027	0.004	-10000	0	-10000	0	0
NR2C1	0.027	0.004	-10000	0	-10000	0	0
MBD3	0.027	0.005	-10000	0	-10000	0	0
MBD2	0.026	0.007	-10000	0	-10000	0	0

×

Atypical 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.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.038	0.021	-10000	0	-0.34	1	1
FBXW11	0.026	0.007	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.026	0.032	0.23	1	-0.28	3	4
NF kappa B1 p50/RelA/I kappa B alpha	0.027	0.053	-10000	0	-10000	0	0
NFKBIA	0.019	0.043	-10000	0	-0.21	7	7
MAPK14	0.027	0.003	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.027	0.012	-10000	0	-10000	0	0
ARRB2	0.014	0.005	-10000	0	-10000	0	0
REL	0.024	0.046	0.27	2	-0.47	3	5
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.027	0.018	-10000	0	-0.27	1	1
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.027	0.011	-10000	0	-10000	0	0
PIK3CA	0.026	0.007	-10000	0	-10000	0	0
NF kappa B1 p50 dimer	0.021	0.018	0.25	2	-10000	0	2
PIK3R1	0.025	0.025	-10000	0	-0.47	1	1
NFKB1	0.013	0.005	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.023	0.04	-10000	0	-0.2	3	3
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.026	0.056	-10000	0	-10000	0	0
SRC	0.026	0.007	-10000	0	-10000	0	0
PI3K	0.035	0.023	-10000	0	-0.34	1	1
NF kappa B1 p50/RelA	0.023	0.041	-10000	0	-0.2	3	3
IKBKB	0.025	0.009	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.007	-10000	0	-10000	0	0
SYK	0.02	0.049	-10000	0	-0.47	4	4
I kappa B alpha/PIK3R1	0.023	0.057	-10000	0	-0.21	8	8
cell death	0.024	0.054	-10000	0	-10000	0	0
NF kappa B1 p105/c-Rel	0.026	0.032	0.23	1	-0.28	3	4
LCK	0.024	0.051	0.21	2	-0.47	4	6
BCL3	0.026	0.025	-10000	0	-0.47	1	1

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.013	0.03	0.15	16	-10000	0	16
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.023	0.026	0.14	2	-10000	0	2
AP2	0.038	0.012	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.033	0.013	-10000	0	-10000	0	0
CLTB	0.026	0.006	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.018	0.011	-10000	0	-10000	0	0
CD4	0.024	0.035	-10000	0	-0.47	2	2
CLTA	0.025	0.009	-10000	0	-10000	0	0
mol:GTP	0	0.003	-10000	0	-10000	0	0
ARFGAP1	0.007	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.007	0.01	-10000	0	-10000	0	0
ARF1/GTP	0.029	0.015	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.011	0.008	-10000	0	-10000	0	0
mol:Choline	0.007	0.01	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.03	0.006	-10000	0	-10000	0	0
DDEF1	0.006	0.01	-10000	0	-10000	0	0
ARF1/GDP	0.007	0.018	-10000	0	-0.086	8	8
AP2M1	0.026	0.007	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.016	0.007	-10000	0	-10000	0	0
Rac/GTP	0.021	0.006	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.038	0.014	-10000	0	-10000	0	0
ARFIP2	0.02	0.014	-10000	0	-10000	0	0
COPA	0.024	0.01	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.025	0.05	0.16	3	-0.18	3	6
ARF1/GTP/ARHGAP10	0.018	0.008	-10000	0	-10000	0	0
GGA3	0.027	0.005	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.026	0.023	-10000	0	-0.22	2	2
AP2A1	0.027	0.005	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.008	0.037	-10000	0	-0.21	6	6
ARF1/GDP/Membrin	0.031	0.027	-10000	0	-0.25	2	2
Arfaptin 2/Rac/GDP	0.032	0.013	-10000	0	-10000	0	0
CYTH2	0.03	0.006	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.038	0.01	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.02	0.005	-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	0.026	0.036	-10000	0	-10000	0	0
PLD2	0.007	0.01	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	0.007	0.002	-10000	0	-10000	0	0
PIP5K1A	0.007	0.01	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.02	0.02	-10000	0	-10000	0	0
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.007	0.01	-10000	0	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.007	0.002	-10000	0	-10000	0	0
GOSR2	0.01	0.024	-10000	0	-0.31	2	2
USO1	0.011	0.018	-10000	0	-0.31	1	1
GBF1	0.008	0.036	-10000	0	-0.31	5	5
ARF1/GTP/Arfaptin 2	0.035	0.012	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.048	0.03	-10000	0	-0.28	2	2

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.039	0.01	-9999	-9999
FBXW11	0.026	0.007	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.007	-9999	-9999
CHUK	0.027	0.005	-9999	-9999
NF kappa B2 p100/RelB	0.072	0.028	-9999	-9999
NFKB1	0.027	0.004	-9999	-9999
MAP3K14	0.027	0.004	-9999	-9999
NF kappa B1 p50/RelB	0.039	0.009	-9999	-9999
RELB	0.027	0.005	-9999	-9999
NFKB2	0.027	0.005	-9999	-9999
NF kappa B2 p52/RelB	0.035	0.009	-9999	-9999
regulation of B cell activation	0.035	0.009	-9999	-9999

pid_entity	TCGA.ZF.AA5P	TCGA.ZF.AA5N	TCGA.ZF.AA5H	TCGA.ZF.AA58
109_MAP3K5	0.035	-0.11	0.054	0.069
47_PPARGC1A	0.028	-0.017	-0.47	-0.47
105_BMP4	0.028	0.028	0.028	0.028
105_BMP6	0.028	0.028	0.028	0.028
105_BMP7	0.028	0.028	-0.47	-0.47
105_BMP2	0.028	0.028	0.028	0.028
131_RELN/VLDLR	0.072	0.064	0.072	-0.26
30_TGFB1/TGF beta receptor Type II	0.026	0.026	0.026	0.027
84_STAT5B	0.024	-0.11	0.097	0.021
84_STAT5A	0.024	-0.11	0.097	0.021