Breast Invasive Carcinoma: PARADIGM pathway analysis of mRNA expression and copy number data

Pathway.Name	Avg.Num.Perturbations
Signaling events regulated by Ret tyrosine kinase	96
Signaling events mediated by Stem cell factor receptor (c-Kit)	93
Endothelins	77
IGF1 pathway	73
Osteopontin-mediated events	70
FOXM1 transcription factor network	70
IL4-mediated signaling events	69
Plasma membrane estrogen receptor signaling	66
EGFR-dependent Endothelin signaling events	64
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	63

Pathway.Name	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
Signaling events regulated by Ret tyrosine kinase	96	7934	82	-0.16	0.036	1000	-1000	-0.038	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	93	7276	78	-0.31	0.13	1000	-1000	-0.023	-1000
Endothelins	77	7431	96	-0.18	0.035	1000	-1000	-0.027	-1000
IGF1 pathway	73	4169	57	-0.079	0.052	1000	-1000	-0.024	-1000
Osteopontin-mediated events	70	2670	38	-0.14	0.04	1000	-1000	-0.015	-1000
FOXM1 transcription factor network	70	3588	51	-0.44	0.034	1000	-1000	-0.055	-1000
IL4-mediated signaling events	69	6346	91	-0.53	0.43	1000	-1000	-0.05	-1000
Plasma membrane estrogen receptor signaling	66	5722	86	-0.22	0.21	1000	-1000	-0.036	-1000
EGFR-dependent Endothelin signaling events	64	1361	21	-0.072	0.048	1000	-1000	-0.003	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	63	4295	68	-0.35	0.15	1000	-1000	-0.039	-1000
Syndecan-1-mediated signaling events	57	1956	34	-0.13	0.042	1000	-1000	-0.026	-1000
Glucocorticoid receptor regulatory network	57	6608	114	-0.39	0.19	1000	-1000	-0.039	-1000
HIF-1-alpha transcription factor network	56	4289	76	-0.18	0.05	1000	-1000	-0.016	-1000
Signaling events mediated by the Hedgehog family	53	2797	52	-0.096	0.052	1000	-1000	-0.016	-1000
Thromboxane A2 receptor signaling	49	5164	105	-0.11	0.062	1000	-1000	-0.029	-1000
Fc-epsilon receptor I signaling in mast cells	49	4827	97	-0.098	0.036	1000	-1000	-0.046	-1000
Wnt signaling	49	344	7	-0.067	0.03	1000	-1000	-0.002	-1000
IL12-mediated signaling events	47	4122	87	-0.26	0.043	1000	-1000	-0.031	-1000
FAS signaling pathway (CD95)	47	2211	47	-0.1	0.049	1000	-1000	-0.025	-1000
Stabilization and expansion of the E-cadherin adherens junction	46	3458	74	-0.095	0.059	1000	-1000	-0.045	-1000
IL23-mediated signaling events	46	2766	60	-0.2	0.036	1000	-1000	-0.045	-1000
Noncanonical Wnt signaling pathway	45	1171	26	-0.067	0.036	1000	-1000	-0.048	-1000
TCR signaling in naïve CD8+ T cells	45	4220	93	-0.072	0.048	1000	-1000	-0.032	-1000
IL27-mediated signaling events	44	2248	51	-0.2	0.099	1000	-1000	-0.048	-1000
Nongenotropic Androgen signaling	43	2271	52	-0.12	0.063	1000	-1000	-0.019	-1000
IL6-mediated signaling events	42	3154	75	-0.14	0.038	1000	-1000	-0.032	-1000
LPA receptor mediated events	40	4086	102	-0.077	0.036	1000	-1000	-0.057	-1000
Signaling mediated by p38-gamma and p38-delta	39	590	15	-0.056	0.033	1000	-1000	-0.026	-1000
Syndecan-4-mediated signaling events	39	2670	67	-0.061	0.087	1000	-1000	-0.029	-1000
E-cadherin signaling in keratinocytes	39	1714	43	-0.062	0.036	1000	-1000	-0.021	-1000
Ephrin B reverse signaling	36	1731	48	-0.12	0.073	1000	-1000	-0.037	-1000
Arf6 signaling events	35	2217	62	-0.069	0.079	1000	-1000	-0.01	-1000
E-cadherin signaling in the nascent adherens junction	35	2712	76	-0.082	0.056	1000	-1000	-0.045	-1000
IL2 signaling events mediated by PI3K	34	2013	58	-0.23	0.036	1000	-1000	-0.035	-1000
E-cadherin signaling events	34	173	5	-0.011	0.028	1000	-1000	0.021	-1000
ErbB4 signaling events	33	2318	69	-0.1	0.059	1000	-1000	-0.023	-1000
TCGA08_p53	33	234	7	-0.028	0.026	1000	-1000	-0.009	-1000
Canonical Wnt signaling pathway	33	1695	51	-0.15	0.09	1000	-1000	-0.034	-1000
Coregulation of Androgen receptor activity	31	2360	76	-0.15	0.054	1000	-1000	-0.034	-1000
PLK2 and PLK4 events	31	93	3	-0.013	0.03	1000	-1000	0.002	-1000
Syndecan-2-mediated signaling events	31	2158	69	-0.019	0.048	1000	-1000	-0.031	-1000
Signaling events mediated by PTP1B	31	2423	76	-0.091	0.062	1000	-1000	-0.024	-1000
Integrins in angiogenesis	30	2577	84	-0.12	0.06	1000	-1000	-0.019	-1000
Cellular roles of Anthrax toxin	29	1133	39	-0.074	0.035	1000	-1000	-0.018	-1000
amb2 Integrin signaling	29	2401	82	-0.049	0.047	1000	-1000	-0.016	-1000
Reelin signaling pathway	28	1575	56	-0.068	0.07	1000	-1000	-0.016	-1000
TCGA08_retinoblastoma	28	231	8	-0.011	0.024	1000	-1000	-0.01	-1000
Caspase cascade in apoptosis	27	2058	74	-0.066	0.047	1000	-1000	-0.025	-1000
Regulation of nuclear SMAD2/3 signaling	27	3797	136	-0.19	0.067	1000	-1000	-0.036	-1000
Visual signal transduction: Rods	27	1405	52	-0.064	0.067	1000	-1000	-0.017	-1000
BMP receptor signaling	26	2184	81	-0.11	0.067	1000	-1000	-0.02	-1000
Nectin adhesion pathway	26	1663	63	-0.047	0.054	1000	-1000	-0.031	-1000
mTOR signaling pathway	25	1371	53	-0.068	0.045	1000	-1000	-0.022	-1000
BCR signaling pathway	25	2521	99	-0.1	0.065	1000	-1000	-0.04	-1000
Aurora B signaling	25	1706	67	-0.062	0.053	1000	-1000	-0.03	-1000
IL1-mediated signaling events	24	1530	62	-0.028	0.075	1000	-1000	-0.024	-1000
PDGFR-alpha signaling pathway	23	1054	44	-0.14	0.05	1000	-1000	-0.024	-1000
IFN-gamma pathway	23	1602	68	-0.061	0.059	1000	-1000	-0.035	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	23	1038	45	-0.041	0.055	1000	-1000	-0.022	-1000
Arf6 downstream pathway	22	961	43	-0.047	0.048	1000	-1000	-0.029	-1000
Ceramide signaling pathway	22	1680	76	-0.069	0.069	1000	-1000	-0.019	-1000
Visual signal transduction: Cones	21	816	38	-0.023	0.051	1000	-1000	0	-1000
Presenilin action in Notch and Wnt signaling	21	1303	61	-0.2	0.071	1000	-1000	-0.033	-1000
Glypican 1 network	21	1041	48	-0.025	0.049	1000	-1000	-0.021	-1000
PLK1 signaling events	21	1837	85	-0.074	0.052	1000	-1000	-0.032	-1000
S1P1 pathway	21	775	36	-0.034	0.036	1000	-1000	-0.019	-1000
Insulin Pathway	21	1580	74	-0.063	0.081	1000	-1000	-0.021	-1000
FOXA2 and FOXA3 transcription factor networks	20	958	46	-0.2	0.043	1000	-1000	-0.055	-1000
TRAIL signaling pathway	20	983	48	-0.022	0.037	1000	-1000	-0.02	-1000
ceramide signaling pathway	20	991	49	-0.057	0.049	1000	-1000	-0.019	-1000
Calcium signaling in the CD4+ TCR pathway	20	644	31	-0.035	0.045	1000	-1000	-0.036	-1000
Class I PI3K signaling events	20	1499	73	-0.061	0.045	1000	-1000	-0.024	-1000
VEGFR1 specific signals	20	1175	56	-0.028	0.036	1000	-1000	-0.034	-1000
EPHB forward signaling	19	1699	85	-0.047	0.11	1000	-1000	-0.043	-1000
PDGFR-beta signaling pathway	19	1917	97	-0.065	0.067	1000	-1000	-0.028	-1000
ErbB2/ErbB3 signaling events	18	1198	65	-0.045	0.048	1000	-1000	-0.079	-1000
RXR and RAR heterodimerization with other nuclear receptor	18	949	52	-0.057	0.063	1000	-1000	-0.02	-1000
Ras signaling in the CD4+ TCR pathway	18	306	17	-0.002	0.05	1000	-1000	-0.014	-1000
EPO signaling pathway	17	970	55	-0.11	0.046	1000	-1000	-0.02	-1000
Syndecan-3-mediated signaling events	17	607	35	-0.031	0.069	1000	-1000	-0.022	-1000
Regulation of Telomerase	17	1754	102	-0.15	0.063	1000	-1000	-0.044	-1000
Aurora A signaling	16	979	60	-0.007	0.05	1000	-1000	-0.008	-1000
p75(NTR)-mediated signaling	16	2022	125	-0.045	0.086	1000	-1000	-0.039	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	15	824	54	-0.035	0.05	1000	-1000	-0.021	-1000
HIF-2-alpha transcription factor network	15	660	43	-0.1	0.11	1000	-1000	-0.034	-1000
S1P3 pathway	15	636	42	-0.016	0.044	1000	-1000	-0.011	-1000
S1P4 pathway	15	399	25	-0.009	0.044	1000	-1000	-0.008	-1000
LPA4-mediated signaling events	14	176	12	-0.029	0.021	1000	-1000	-0.018	-1000
Hedgehog signaling events mediated by Gli proteins	14	954	65	-0.022	0.076	1000	-1000	-0.032	-1000
Atypical NF-kappaB pathway	14	453	31	-0.017	0.036	1000	-1000	-0.009	-1000
Signaling events mediated by VEGFR1 and VEGFR2	14	1753	125	-0.025	0.045	1000	-1000	-0.016	-1000
Regulation of Androgen receptor activity	14	1036	70	-0.14	0.048	1000	-1000	-0.033	-1000
Sphingosine 1-phosphate (S1P) pathway	13	383	28	-0.009	0.044	1000	-1000	-0.002	-1000
S1P5 pathway	13	236	17	-0.001	0.035	1000	-1000	-0.012	-1000
Retinoic acid receptors-mediated signaling	13	786	58	-0.071	0.068	1000	-1000	-0.026	-1000
Signaling mediated by p38-alpha and p38-beta	13	576	44	-0.055	0.056	1000	-1000	-0.012	-1000
Regulation of p38-alpha and p38-beta	13	711	54	-0.018	0.073	1000	-1000	-0.02	-1000
Glypican 2 network	13	54	4	0	0.014	1000	-1000	0	-1000
IL2 signaling events mediated by STAT5	13	291	22	-0.024	0.037	1000	-1000	-0.022	-1000
Neurotrophic factor-mediated Trk receptor signaling	13	1602	120	-0.077	0.09	1000	-1000	-0.037	-1000
p38 MAPK signaling pathway	13	584	44	-0.051	0.058	1000	-1000	-0.013	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	12	1102	85	-0.14	0.064	1000	-1000	-0.031	-1000
FoxO family signaling	12	807	64	-0.092	0.049	1000	-1000	-0.023	-1000
Nephrin/Neph1 signaling in the kidney podocyte	11	374	34	-0.039	0.076	1000	-1000	-0.033	-1000
Paxillin-independent events mediated by a4b1 and a4b7	11	413	37	-0.024	0.073	1000	-1000	-0.02	-1000
TCGA08_rtk_signaling	11	292	26	-0.026	0.043	1000	-1000	-0.011	-1000
Angiopoietin receptor Tie2-mediated signaling	11	1054	88	-0.063	0.063	1000	-1000	-0.051	-1000
BARD1 signaling events	10	582	57	-0.048	0.07	1000	-1000	-0.043	-1000
Signaling events mediated by HDAC Class III	10	411	40	-0.064	0.065	1000	-1000	-0.041	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	10	844	83	-0.057	0.069	1000	-1000	-0.01	-1000
Paxillin-dependent events mediated by a4b1	10	379	36	-0.061	0.064	1000	-1000	-0.038	-1000
Effects of Botulinum toxin	10	273	26	-0.062	0.051	1000	-1000	-0.001	-1000
Signaling events mediated by PRL	10	357	34	-0.038	0.051	1000	-1000	-0.027	-1000
Signaling events mediated by HDAC Class II	9	691	75	-0.089	0.076	1000	-1000	-0.026	-1000
a4b1 and a4b7 Integrin signaling	9	49	5	0.021	0.042	1000	-1000	0.024	-1000
Class IB PI3K non-lipid kinase events	9	27	3	-0.026	0.026	1000	-1000	-0.025	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	8	279	33	-0.015	0.072	1000	-1000	-0.025	-1000
JNK signaling in the CD4+ TCR pathway	7	122	17	-0.01	0.08	1000	-1000	-0.017	-1000
Class I PI3K signaling events mediated by Akt	7	529	68	-0.053	0.076	1000	-1000	-0.019	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	6	139	23	0	0.055	1000	-1000	-0.011	-1000
Ephrin A reverse signaling	6	44	7	0	0.042	1000	-1000	0	-1000
Insulin-mediated glucose transport	6	211	32	0	0.042	1000	-1000	-0.008	-1000
Canonical NF-kappaB pathway	5	195	39	0	0.074	1000	-1000	-0.01	-1000
Arf6 trafficking events	5	406	71	-0.041	0.043	1000	-1000	-0.026	-1000
Alternative NF-kappaB pathway	5	77	13	0	0.082	1000	-1000	0	-1000
Circadian rhythm pathway	4	101	22	-0.01	0.067	1000	-1000	-0.035	-1000
Aurora C signaling	3	22	7	0	0.054	1000	-1000	-0.006	-1000
Signaling events mediated by HDAC Class I	3	365	104	-0.047	0.081	1000	-1000	-0.029	-1000
Arf1 pathway	3	196	54	-0.001	0.062	1000	-1000	-0.011	-1000
Rapid glucocorticoid signaling	2	55	20	-0.001	0.044	1000	-1000	0	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0	18	27	0	0.081	1000	-1000	-0.021	-1000
Total	3452	212603	7203	-11	8	131000	-131000	-3.2	-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	-0.038	0.13	-10000	0	-0.52	30	30
Crk/p130 Cas/Paxillin	-0.13	0.16	-10000	0	-0.33	166	166
JUN	-0.13	0.18	0.19	2	-0.4	113	115
HRAS	0.032	0.036	-10000	0	-0.42	3	3
RET51/GFRalpha1/GDNF/GRB10	-0.1	0.2	-10000	0	-0.31	228	228
RAP1A	0.031	0.045	-10000	0	-0.42	5	5
FRS2	0.033	0.022	-10000	0	-0.42	1	1
RAP1A/GDP	0.023	0.032	-10000	0	-0.3	5	5
RET51/GFRalpha1/GDNF/DOK1	-0.097	0.21	-10000	0	-0.32	220	220
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.036	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.032	0.023	-10000	0	-0.42	1	1
RET9/GFRalpha1/GDNF/Enigma	-0.041	0.14	-10000	0	-0.23	171	171
RHOA	0.026	0.061	-10000	0	-0.42	9	9
RAP1A/GTP	-0.093	0.18	-10000	0	-0.28	221	221
GRB7	0.024	0.058	-10000	0	-0.42	8	8
RET51/GFRalpha1/GDNF	-0.092	0.2	-10000	0	-0.31	217	217
MAPKKK cascade	-0.11	0.19	-10000	0	-0.32	203	203
BCAR1	0.03	0.014	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.064	0.17	-10000	0	-0.28	181	181
lamellipodium assembly	-0.11	0.16	-10000	0	-0.3	173	173
RET51/GFRalpha1/GDNF/SHC	-0.08	0.18	-10000	0	-0.29	195	195
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
RET9/GFRalpha1/GDNF/SHC	-0.028	0.12	-10000	0	-0.23	123	123
RET9/GFRalpha1/GDNF/Shank3	-0.042	0.14	-10000	0	-0.23	174	174
MAPK3	-0.11	0.15	0.24	3	-0.38	90	93
DOK1	0.027	0.061	-10000	0	-0.42	9	9
DOK6	0.005	0.11	-10000	0	-0.42	31	31
PXN	0.036	0.004	-10000	0	-10000	0	0
neurite development	-0.11	0.16	0.28	2	-0.37	102	104
DOK5	0.012	0.089	-10000	0	-0.42	20	20
GFRA1	-0.13	0.21	-10000	0	-0.42	177	177
MAPK8	-0.12	0.18	-10000	0	-0.3	218	218
HRAS/GTP	-0.11	0.22	-10000	0	-0.35	217	217
tube development	-0.03	0.14	0.22	24	-0.22	163	187
MAPK1	-0.12	0.16	0.24	3	-0.38	90	93
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.053	0.12	-10000	0	-0.22	157	157
Rac1/GDP	0.026	0.004	-10000	0	-10000	0	0
SRC	0.033	0.029	-10000	0	-0.42	2	2
PDLIM7	0.035	0.007	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.093	0.21	-10000	0	-0.32	220	220
SHC1	0.028	0.025	-10000	0	-0.42	1	1
RET51/GFRalpha1/GDNF/Dok4	-0.1	0.2	-10000	0	-0.31	220	220
RET51/GFRalpha1/GDNF/Dok5	-0.1	0.2	-10000	0	-0.32	213	213
PRKCA	0.032	0.012	-10000	0	-10000	0	0
HRAS/GDP	0.024	0.025	-10000	0	-0.3	3	3
CREB1	-0.086	0.17	-10000	0	-0.33	147	147
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.039	0.11	-10000	0	-0.23	115	115
RET51/GFRalpha1/GDNF/Grb7	-0.095	0.2	-10000	0	-0.32	211	211
mol:GDP	0	0	-10000	0	-10000	0	0
RET	-0.095	0.2	-10000	0	-0.42	137	137
DOK4	0.028	0.032	-10000	0	-0.42	2	2
JNK cascade	-0.13	0.17	0.19	2	-0.4	113	115
RET9/GFRalpha1/GDNF/FRS2	-0.042	0.14	-10000	0	-0.23	169	169
SHANK3	0.035	0.029	-10000	0	-0.42	2	2
RASA1	0.029	0.05	-10000	0	-0.42	6	6
NCK1	0.034	0.021	-10000	0	-0.42	1	1
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.036	0.1	-10000	0	-0.22	114	114
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.1	0.18	-10000	0	-0.3	205	205
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.12	0.19	-10000	0	-0.31	220	220
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.11	0.19	-10000	0	-0.34	181	181
PI3K	-0.16	0.25	0.24	1	-0.46	173	174
SOS1	0.035	0.021	-10000	0	-0.42	1	1
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.028	0.14	-10000	0	-0.22	163	163
GRB10	0.023	0.075	-10000	0	-0.42	14	14
activation of MAPKK activity	-0.081	0.15	-10000	0	-0.33	93	93
RET51/GFRalpha1/GDNF/FRS2	-0.095	0.2	-10000	0	-0.31	216	216
GAB1	0.027	0.061	-10000	0	-0.42	9	9
IRS1	-0.014	0.14	-10000	0	-0.42	54	54
IRS2	0.008	0.099	-10000	0	-0.42	25	25
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.12	0.2	-10000	0	-0.35	186	186
RET51/GFRalpha1/GDNF/PKC alpha	-0.089	0.2	-10000	0	-0.32	200	200
GRB2	0.033	0.011	-10000	0	-10000	0	0
PRKACA	0.036	0.005	-10000	0	-10000	0	0
GDNF	0.032	0.036	-10000	0	-0.42	3	3
RAC1	0.035	0.006	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.12	0.23	-10000	0	-0.35	226	226
Rac1/GTP	-0.12	0.2	-10000	0	-0.36	170	170
RET9/GFRalpha1/GDNF	-0.06	0.14	-10000	0	-0.25	172	172
GFRalpha1/GDNF	-0.074	0.16	-10000	0	-0.3	172	172

×

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

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
MAP4K1	-0.12	0.19	0.38	1	-0.41	134	135
CRKL	-0.13	0.2	-10000	0	-0.42	139	139
HRAS	-0.077	0.17	-10000	0	-0.36	97	97
mol:PIP3	-0.088	0.2	0.28	2	-0.41	105	107
SPRED1	0.02	0.08	-10000	0	-0.42	16	16
SPRED2	0.02	0.082	-10000	0	-0.42	17	17
GAB1	-0.14	0.21	-10000	0	-0.44	138	138
FOXO3	-0.1	0.2	-10000	0	-0.4	126	126
AKT1	-0.11	0.22	-10000	0	-0.43	124	124
BAD	-0.1	0.2	-10000	0	-0.4	118	118
megakaryocyte differentiation	-0.13	0.21	-10000	0	-0.44	135	135
GSK3B	-0.1	0.2	0.34	1	-0.4	123	124
RAF1	-0.056	0.15	0.26	4	-0.3	87	91
SHC1	0.028	0.025	-10000	0	-0.42	1	1
STAT3	-0.12	0.2	-10000	0	-0.43	133	133
STAT1	-0.31	0.48	-10000	0	-0.88	185	185
HRAS/SPRED1	-0.054	0.16	0.26	1	-0.32	94	95
cell proliferation	-0.13	0.21	-10000	0	-0.43	136	136
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
TEC	0.031	0.045	-10000	0	-0.42	5	5
RPS6KB1	-0.13	0.22	-10000	0	-0.45	135	135
HRAS/SPRED2	-0.053	0.16	0.26	1	-0.31	95	96
LYN/TEC/p62DOK	-0.092	0.22	-10000	0	-0.42	124	124
MAPK3	-0.034	0.12	0.25	7	-0.25	37	44
STAP1	-0.13	0.21	-10000	0	-0.44	135	135
GRAP2	0.032	0.023	-10000	0	-0.42	1	1
JAK2	-0.26	0.41	-10000	0	-0.73	192	192
STAT1 (dimer)	-0.3	0.46	-10000	0	-0.86	185	185
mol:Gleevec	0.005	0.008	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.099	0.22	-10000	0	-0.42	127	127
actin filament polymerization	-0.13	0.21	-10000	0	-0.43	135	135
LYN	0.03	0.014	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.19	0.3	-10000	0	-0.54	187	187
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
CBL/CRKL/GRB2	-0.1	0.2	-10000	0	-0.39	129	129
PI3K	-0.1	0.23	-10000	0	-0.45	126	126
PTEN	0.027	0.061	-10000	0	-0.42	9	9
SCF/KIT/EPO/EPOR	-0.3	0.53	-10000	0	-1.1	128	128
MAPK8	-0.13	0.21	-10000	0	-0.44	136	136
STAT3 (dimer)	-0.12	0.2	-10000	0	-0.42	133	133
positive regulation of transcription	-0.025	0.1	0.23	8	-0.21	32	40
mol:GDP	-0.083	0.17	-10000	0	-0.37	96	96
PIK3C2B	-0.12	0.2	-10000	0	-0.41	129	129
CBL/CRKL	-0.12	0.2	-10000	0	-0.41	135	135
FER	-0.13	0.21	-10000	0	-0.44	134	134
SH2B3	-0.13	0.21	-10000	0	-0.44	135	135
PDPK1	-0.07	0.19	0.31	12	-0.38	96	108
SNAI2	-0.14	0.22	-10000	0	-0.46	137	137
positive regulation of cell proliferation	-0.22	0.36	-10000	0	-0.68	167	167
KITLG	-0.051	0.16	-10000	0	-0.44	72	72
cell motility	-0.22	0.36	-10000	0	-0.68	167	167
PTPN6	0.038	0.032	-10000	0	-0.41	2	2
EPOR	-0.068	0.18	-10000	0	-0.75	10	10
STAT5A (dimer)	-0.19	0.3	-10000	0	-0.55	184	184
SOCS1	0.032	0.023	-10000	0	-0.42	1	1
cell migration	0.13	0.21	0.44	135	-10000	0	135
SOS1	0.035	0.021	-10000	0	-0.42	1	1
EPO	0.012	0.029	-10000	0	-10000	0	0
VAV1	0.019	0.082	-10000	0	-0.42	17	17
GRB10	-0.14	0.21	-10000	0	-0.45	136	136
PTPN11	0.041	0.009	-10000	0	-10000	0	0
SCF/KIT	-0.14	0.22	-10000	0	-0.46	135	135
GO:0007205	0.007	0.011	-10000	0	-10000	0	0
MAP2K1	-0.042	0.13	0.24	6	-0.25	73	79
CBL	0.032	0.012	-10000	0	-10000	0	0
KIT	-0.27	0.53	-10000	0	-1.3	102	102
MAP2K2	-0.043	0.13	0.27	7	-0.25	75	82
SHC/Grb2/SOS1	-0.08	0.2	-10000	0	-0.41	99	99
STAT5A	-0.2	0.32	-10000	0	-0.57	184	184
GRB2	0.033	0.011	-10000	0	-10000	0	0
response to radiation	-0.14	0.22	-10000	0	-0.45	138	138
SHC/GRAP2	0.038	0.032	-10000	0	-0.3	2	2
PTPRO	-0.14	0.21	-10000	0	-0.45	134	134
SH2B2	-0.13	0.21	-10000	0	-0.44	135	135
DOK1	0.027	0.061	-10000	0	-0.42	9	9
MATK	-0.13	0.21	-10000	0	-0.44	135	135
CREBBP	-0.008	0.08	-10000	0	-0.12	161	161
BCL2	-0.3	0.56	-10000	0	-1.3	114	114

×

Endothelins

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
AKT1	-0.011	0.19	0.27	72	-0.33	93	165
PTK2B	0.028	0.015	-10000	0	-10000	0	0
mol:Ca2+	-0.056	0.26	-10000	0	-0.65	55	55
EDN1	-0.01	0.19	0.23	65	-0.43	65	130
EDN3	-0.011	0.12	-10000	0	-0.42	38	38
EDN2	-0.054	0.18	-10000	0	-0.42	93	93
HRAS/GDP	-0.065	0.23	0.28	4	-0.45	101	105
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.059	0.2	-10000	0	-0.4	101	101
ADCY4	-0.011	0.17	0.26	8	-0.42	40	48
ADCY5	-0.015	0.16	0.23	4	-0.39	44	48
ADCY6	-0.01	0.16	0.26	6	-0.39	44	50
ADCY7	-0.013	0.16	0.27	4	-0.38	42	46
ADCY1	-0.009	0.16	0.25	7	-0.38	43	50
ADCY2	-0.026	0.17	0.26	5	-0.39	61	66
ADCY3	-0.01	0.16	0.26	9	-0.38	47	56
ADCY8	-0.006	0.14	0.26	4	-0.36	38	42
ADCY9	-0.013	0.16	0.24	8	-0.38	44	52
arachidonic acid secretion	-0.089	0.26	0.28	1	-0.5	114	115
ETB receptor/Endothelin-1/Gq/GTP	-0.05	0.16	-10000	0	-0.32	106	106
GNAO1	0.03	0.014	-10000	0	-10000	0	0
HRAS	0.032	0.036	-10000	0	-0.42	3	3
ETA receptor/Endothelin-1/G12/GTP	0.03	0.21	0.37	72	-0.31	87	159
ETA receptor/Endothelin-1/Gs/GTP	0.025	0.2	0.35	71	-0.32	75	146
mol:GTP	-0.001	0.006	-10000	0	-10000	0	0
COL3A1	-0.016	0.21	0.27	73	-0.42	71	144
EDNRB	0.003	0.097	-10000	0	-0.37	25	25
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.008	0.2	0.27	68	-0.5	39	107
CYSLTR1	-0.025	0.23	0.27	70	-0.55	53	123
SLC9A1	-0.004	0.13	0.19	72	-0.3	40	112
mol:GDP	-0.081	0.24	0.26	6	-0.47	107	113
SLC9A3	-0.12	0.35	-10000	0	-0.7	109	109
RAF1	-0.094	0.24	-10000	0	-0.48	114	114
JUN	-0.098	0.36	-10000	0	-0.94	63	63
JAK2	-0.008	0.19	0.27	73	-0.33	89	162
mol:IP3	-0.074	0.21	0.23	1	-0.42	104	105
ETA receptor/Endothelin-1	0.014	0.25	0.42	72	-0.38	101	173
PLCB1	-0.023	0.14	-10000	0	-0.42	59	59
PLCB2	0.032	0.023	-10000	0	-0.43	1	1
ETA receptor/Endothelin-3	0	0.15	-10000	0	-0.32	72	72
FOS	-0.14	0.36	-10000	0	-0.87	87	87
Gai/GDP	-0.11	0.32	-10000	0	-0.72	101	101
CRK	0.032	0.023	-10000	0	-0.42	1	1
mol:Ca ++	-0.089	0.27	0.25	9	-0.5	112	121
BCAR1	0.03	0.014	-10000	0	-10000	0	0
PRKCB1	-0.077	0.22	0.26	12	-0.44	104	116
GNAQ	-0.001	0.007	-10000	0	-10000	0	0
GNAZ	0.023	0.07	-10000	0	-0.42	12	12
GNAL	0.031	0.036	-10000	0	-0.42	3	3
Gs family/GDP	-0.064	0.22	0.26	4	-0.44	101	105
ETA receptor/Endothelin-1/Gq/GTP	-0.041	0.2	0.2	44	-0.4	85	129
MAPK14	-0.068	0.17	0.23	1	-0.35	98	99
TRPC6	-0.061	0.28	-10000	0	-0.7	54	54
GNAI2	0.028	0.054	-10000	0	-0.42	7	7
GNAI3	0.035	0.006	-10000	0	-10000	0	0
GNAI1	0.017	0.087	-10000	0	-0.42	19	19
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.067	0.18	-10000	0	-0.35	109	109
ETB receptor/Endothelin-2	-0.04	0.15	-10000	0	-0.31	111	111
ETB receptor/Endothelin-3	-0.009	0.11	-10000	0	-0.3	57	57
ETB receptor/Endothelin-1	-0.012	0.17	-10000	0	-0.31	99	99
MAPK3	-0.14	0.34	-10000	0	-0.76	98	98
MAPK1	-0.14	0.34	-10000	0	-0.78	96	96
Rac1/GDP	-0.062	0.23	0.27	6	-0.45	100	106
cAMP biosynthetic process	-0.004	0.17	0.28	14	-0.4	43	57
MAPK8	-0.072	0.3	-10000	0	-0.67	75	75
SRC	0.033	0.03	-10000	0	-0.42	2	2
ETB receptor/Endothelin-1/Gi/GTP	-0.043	0.15	-10000	0	-0.33	86	86
p130Cas/CRK/Src/PYK2	-0.1	0.26	-10000	0	-0.55	100	100
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.062	0.23	0.28	5	-0.46	97	102
COL1A2	-0.074	0.3	0.28	52	-0.54	117	169
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.031	0.18	-10000	0	-0.32	122	122
mol:DAG	-0.074	0.21	0.23	1	-0.42	103	104
MAP2K2	-0.11	0.28	0.33	1	-0.58	108	109
MAP2K1	-0.11	0.28	0.3	2	-0.58	111	113
EDNRA	0.016	0.17	0.23	67	-0.44	45	112
positive regulation of muscle contraction	-0.012	0.17	0.23	73	-0.34	62	135
Gq family/GDP	-0.058	0.22	-10000	0	-0.45	88	88
HRAS/GTP	-0.08	0.23	-10000	0	-0.45	103	103
PRKCH	-0.075	0.21	0.23	4	-0.42	101	105
RAC1	0.035	0.006	-10000	0	-10000	0	0
PRKCA	-0.061	0.21	0.24	22	-0.42	94	116
PRKCB	-0.074	0.2	0.22	1	-0.41	106	107
PRKCE	-0.076	0.2	0.22	1	-0.42	101	102
PRKCD	-0.075	0.2	0.22	1	-0.42	98	99
PRKCG	-0.079	0.21	0.22	1	-0.42	101	102
regulation of vascular smooth muscle contraction	-0.18	0.42	-10000	0	-1.1	85	85
PRKCQ	-0.069	0.2	0.23	7	-0.42	99	106
PLA2G4A	-0.099	0.28	0.28	1	-0.54	114	115
GNA14	-0.012	0.13	-10000	0	-0.42	43	43
GNA15	0.026	0.048	-10000	0	-0.42	5	5
GNA12	0.035	0.007	-10000	0	-10000	0	0
GNA11	0.029	0.039	-10000	0	-0.42	3	3
Rac1/GTP	0.03	0.21	0.37	72	-0.31	88	160
MMP1	-0.17	0.35	-10000	0	-0.78	120	120

×

IGF1 pathway

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
NCK2	0.036	0.005	-10000	0	-10000	0	0
PTK2	0.028	0.016	-10000	0	-10000	0	0
CRKL	-0.071	0.15	0.17	2	-0.29	145	147
GRB2/SOS1/SHC	0.052	0.036	-10000	0	-0.26	1	1
HRAS	0.032	0.036	-10000	0	-0.42	3	3
IRS1/Crk	-0.064	0.16	-10000	0	-0.28	151	151
IGF-1R heterotetramer/IGF1/PTP1B	-0.036	0.16	-10000	0	-0.29	132	132
AKT1	-0.077	0.14	0.17	14	-0.28	125	139
BAD	-0.075	0.13	0.16	14	-0.35	59	73
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.068	0.15	0.17	2	-0.3	130	132
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.06	0.16	-10000	0	-0.3	142	142
RAF1	-0.037	0.14	0.29	1	-0.49	14	15
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.025	0.17	-10000	0	-0.29	129	129
YWHAZ	0.027	0.016	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.063	0.17	0.17	2	-0.3	152	154
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
RPS6KB1	-0.071	0.13	0.17	12	-0.29	107	119
GNB2L1	0.034	0.035	-10000	0	-0.42	3	3
positive regulation of MAPKKK cascade	-0.023	0.14	0.3	10	-0.39	15	25
PXN	0.036	0.004	-10000	0	-10000	0	0
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.048	0.023	-10000	0	-0.3	1	1
HRAS/GTP	-0.04	0.13	-10000	0	-0.26	114	114
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.003	0.13	-10000	0	-0.24	103	103
IGF-1R heterotetramer	-0.061	0.18	-10000	0	-0.46	84	84
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.043	0.17	-10000	0	-0.28	151	151
Crk/p130 Cas/Paxillin	-0.039	0.16	-10000	0	-0.27	142	142
IGF1R	-0.061	0.18	-10000	0	-0.46	84	84
IGF1	-0.06	0.18	-10000	0	-0.46	78	78
IRS2/Crk	-0.071	0.16	0.17	2	-0.29	150	152
PI3K	-0.038	0.17	-10000	0	-0.29	145	145
apoptosis	0.05	0.11	0.31	46	-0.3	4	50
HRAS/GDP	0.024	0.025	-10000	0	-0.3	3	3
PRKCD	-0.062	0.18	0.21	1	-0.34	129	130
RAF1/14-3-3 E	-0.018	0.13	0.29	4	-0.43	13	17
BAD/14-3-3	-0.053	0.12	0.31	4	-0.33	46	50
PRKCZ	-0.075	0.14	0.16	14	-0.27	135	149
Crk/p130 Cas/Paxillin/FAK1	-0.031	0.13	-10000	0	-0.34	44	44
PTPN1	0.03	0.031	-10000	0	-0.42	2	2
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.075	0.18	-10000	0	-0.35	130	130
BCAR1	0.03	0.014	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.018	0.14	-10000	0	-0.26	122	122
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.035	0.021	-10000	0	-0.42	1	1
IRS1/NCK2	-0.054	0.16	-10000	0	-0.28	151	151
GRB10	0.023	0.075	-10000	0	-0.42	14	14
PTPN11	-0.072	0.15	0.17	2	-0.29	142	144
IRS1	-0.075	0.16	-10000	0	-0.3	152	152
IRS2	-0.079	0.16	0.17	2	-0.3	151	153
IGF-1R heterotetramer/IGF1	-0.072	0.19	-10000	0	-0.37	140	140
GRB2	0.033	0.011	-10000	0	-10000	0	0
PDPK1	-0.075	0.14	0.18	14	-0.28	135	149
YWHAE	0.032	0.012	-10000	0	-10000	0	0
PRKD1	-0.071	0.2	0.21	5	-0.37	126	131
SHC1	0.028	0.025	-10000	0	-0.42	1	1

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.037	0.15	0.36	1	-0.27	130	131
NF kappa B1 p50/RelA/I kappa B alpha	-0.034	0.17	0.33	1	-0.4	54	55
alphaV/beta3 Integrin/Osteopontin/Src	-0.043	0.16	-10000	0	-0.32	125	125
AP1	-0.085	0.23	-10000	0	-0.48	90	90
ILK	-0.046	0.14	0.38	1	-0.26	125	126
bone resorption	-0.053	0.14	-10000	0	-0.34	47	47
PTK2B	0.028	0.015	-10000	0	-10000	0	0
PYK2/p130Cas	-0.027	0.16	-10000	0	-0.26	134	134
ITGAV	0.018	0.082	-10000	0	-0.43	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.04	0.064	-10000	0	-0.3	17	17
alphaV/beta3 Integrin/Osteopontin	-0.022	0.16	-10000	0	-0.28	127	127
MAP3K1	-0.059	0.14	0.29	2	-0.27	142	144
JUN	-0.001	0.12	-10000	0	-0.42	39	39
MAPK3	-0.059	0.14	0.23	6	-0.27	127	133
MAPK1	-0.064	0.15	0.23	6	-0.28	140	146
Rac1/GDP	0.026	0.004	-10000	0	-10000	0	0
NFKB1	0.036	0.005	-10000	0	-10000	0	0
MAPK8	-0.064	0.13	0.22	8	-0.25	142	150
ITGB3	0.024	0.051	-10000	0	-0.43	5	5
NFKBIA	-0.068	0.16	0.35	3	-0.42	59	62
FOS	-0.031	0.15	-10000	0	-0.42	66	66
CD44	0.022	0.075	-10000	0	-0.42	14	14
CHUK	0.026	0.067	-10000	0	-0.42	11	11
PLAU	-0.14	0.36	-10000	0	-1.1	54	54
NF kappa B1 p50/RelA	-0.022	0.19	-10000	0	-0.45	56	56
BCAR1	0.03	0.014	-10000	0	-10000	0	0
RELA	0.035	0.006	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.031	0.081	-10000	0	-0.31	21	21
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.06	0.15	0.22	7	-0.28	146	153
VAV3	-0.099	0.15	0.22	8	-0.27	203	211
MAP3K14	-0.049	0.14	0.25	4	-0.27	127	131
ROCK2	0.033	0.035	-10000	0	-0.42	3	3
SPP1	-0.076	0.19	-10000	0	-0.42	115	115
RAC1	0.035	0.006	-10000	0	-10000	0	0
Rac1/GTP	-0.082	0.15	0.19	1	-0.25	200	201
MMP2	-0.1	0.19	-10000	0	-0.45	88	88

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.24	0.52	-9999	-1.2	81	81
PLK1	0.017	0.098	-9999	-1.1	3	3
BIRC5	-0.087	0.39	-9999	-1.4	41	41
HSPA1B	-0.25	0.52	-9999	-1.1	98	98
MAP2K1	0.005	0.057	-9999	-10000	0	0
BRCA2	-0.27	0.54	-9999	-1.2	94	94
FOXM1	-0.39	0.86	-9999	-1.8	98	98
XRCC1	-0.24	0.52	-9999	-1.2	84	84
FOXM1B/p19	-0.3	0.58	-9999	-1.3	100	100
Cyclin D1/CDK4	-0.29	0.53	-9999	-1	136	136
CDC2	-0.27	0.56	-9999	-1.3	85	85
TGFA	-0.28	0.5	-9999	-1	116	116
SKP2	-0.24	0.52	-9999	-1.2	82	82
CCNE1	0.024	0.05	-9999	-0.43	5	5
CKS1B	-0.22	0.53	-9999	-1.2	81	81
RB1	-0.15	0.4	-9999	-1	67	67
FOXM1C/SP1	-0.3	0.62	-9999	-1.3	102	102
AURKB	-0.08	0.31	-9999	-0.93	54	54
CENPF	-0.23	0.56	-9999	-1.2	84	84
CDK4	0.016	0.037	-9999	-10000	0	0
MYC	-0.23	0.45	-9999	-0.99	95	95
CHEK2	0.001	0.066	-9999	-0.45	3	3
ONECUT1	-0.28	0.52	-9999	-1.1	105	105
CDKN2A	0.014	0.075	-9999	-0.42	14	14
LAMA4	-0.25	0.53	-9999	-1.2	84	84
FOXM1B/HNF6	-0.35	0.65	-9999	-1.4	105	105
FOS	-0.33	0.6	-9999	-1.2	131	131
SP1	0.034	0.024	-9999	-0.42	1	1
CDC25B	-0.25	0.52	-9999	-1.2	84	84
response to radiation	-0.004	0.032	-9999	-10000	0	0
CENPB	-0.24	0.52	-9999	-1.2	84	84
CENPA	-0.27	0.55	-9999	-1.2	92	92
NEK2	-0.26	0.58	-9999	-1.2	100	100
HIST1H2BA	-0.25	0.52	-9999	-1.2	86	86
CCNA2	0.005	0.11	-9999	-0.43	28	28
EP300	0.032	0.03	-9999	-0.42	2	2
CCNB1/CDK1	-0.32	0.65	-9999	-1.5	86	86
CCNB2	-0.26	0.53	-9999	-1.2	86	86
CCNB1	-0.27	0.57	-9999	-1.3	86	86
ETV5	-0.25	0.53	-9999	-1.2	85	85
ESR1	-0.44	0.65	-9999	-1.2	206	206
CCND1	-0.32	0.52	-9999	-1.1	137	137
GSK3A	0.008	0.052	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.022	0.11	-9999	-0.33	29	29
CDK2	0.03	0.034	-9999	-0.43	2	2
G2/M transition of mitotic cell cycle	-0.006	0.036	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.27	0.57	-9999	-1.2	98	98
GAS1	-0.32	0.59	-9999	-1.2	118	118
MMP2	-0.28	0.57	-9999	-1.3	98	98
RB1/FOXM1C	-0.3	0.55	-9999	-1.1	132	132
CREBBP	0.033	0.011	-9999	-10000	0	0

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.37	0.64	-10000	0	-1.3	138	138
STAT6 (cleaved dimer)	-0.38	0.65	-10000	0	-1.3	142	142
IGHG1	-0.083	0.24	-10000	0	-0.42	72	72
IGHG3	-0.36	0.61	-10000	0	-1.2	144	144
AKT1	-0.12	0.32	-10000	0	-0.77	50	50
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.066	0.26	-10000	0	-0.8	25	25
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.14	0.36	-10000	0	-0.84	58	58
THY1	-0.38	0.66	-10000	0	-1.3	135	135
MYB	-0.055	0.18	-10000	0	-0.42	97	97
HMGA1	0.034	0.029	-10000	0	-0.42	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.14	0.35	-10000	0	-0.66	97	97
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.12	0.33	-10000	0	-0.86	38	38
SP1	0.023	0.052	-10000	0	-0.21	5	5
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.019	0.056	-10000	0	-0.42	4	4
STAT6 (dimer)/ETS1	-0.37	0.64	-10000	0	-1.3	140	140
SOCS1	-0.2	0.39	-10000	0	-0.75	126	126
SOCS3	-0.12	0.32	-10000	0	-0.94	25	25
FCER2	-0.23	0.46	-10000	0	-0.93	100	100
PARP14	0.03	0.051	-10000	0	-0.42	6	6
CCL17	-0.43	0.71	-10000	0	-1.4	155	155
GRB2	0.033	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.076	0.26	-10000	0	-0.7	30	30
T cell proliferation	-0.38	0.67	-10000	0	-1.3	140	140
IL4R/JAK1	-0.37	0.65	-10000	0	-1.3	136	136
EGR2	-0.41	0.7	-10000	0	-1.4	148	148
JAK2	-0.005	0.07	-10000	0	-0.46	2	2
JAK3	0.039	0.014	-10000	0	-10000	0	0
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
JAK1	0.018	0.048	-10000	0	-0.41	3	3
COL1A2	-0.22	0.54	-10000	0	-1.5	72	72
CCL26	-0.37	0.64	-10000	0	-1.3	135	135
IL4R	-0.4	0.71	-10000	0	-1.4	135	135
PTPN6	0.022	0.045	-10000	0	-0.41	2	2
IL13RA2	-0.41	0.68	-10000	0	-1.3	153	153
IL13RA1	-0.009	0.087	-10000	0	-0.46	8	8
IRF4	-0.005	0.16	-10000	0	-1	5	5
ARG1	-0.066	0.26	-10000	0	-0.88	25	25
CBL	-0.14	0.32	-10000	0	-0.62	95	95
GTF3A	0.024	0.046	-10000	0	-0.11	28	28
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
IL13RA1/JAK2	-0.001	0.1	-10000	0	-0.36	8	8
IRF4/BCL6	-0.005	0.16	-10000	0	-0.97	5	5
CD40LG	0.039	0.038	-10000	0	-0.29	5	5
MAPK14	-0.14	0.33	-10000	0	-0.65	89	89
mitosis	-0.11	0.31	-10000	0	-0.72	49	49
STAT6	-0.48	0.88	-10000	0	-1.7	143	143
SPI1	0.033	0.051	-10000	0	-0.25	13	13
RPS6KB1	-0.093	0.3	-10000	0	-0.72	43	43
STAT6 (dimer)	-0.48	0.88	-10000	0	-1.6	143	143
STAT6 (dimer)/PARP14	-0.42	0.73	-10000	0	-1.4	142	142
mast cell activation	0.005	0.017	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.14	0.34	-10000	0	-0.74	71	71
FRAP1	-0.12	0.32	-10000	0	-0.77	49	49
LTA	-0.37	0.64	-10000	0	-1.3	138	138
FES	0.03	0.046	-10000	0	-0.42	5	5
T-helper 1 cell differentiation	0.43	0.78	1.5	143	-10000	0	143
CCL11	-0.4	0.66	-10000	0	-1.3	146	146
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.1	0.31	-10000	0	-0.84	32	32
IL2RG	0.034	0.042	-10000	0	-0.41	4	4
IL10	-0.33	0.65	-10000	0	-1.3	119	119
IRS1	-0.014	0.14	-10000	0	-0.42	54	54
IRS2	0.008	0.099	-10000	0	-0.42	25	25
IL4	-0.063	0.29	-10000	0	-1.3	18	18
IL5	-0.37	0.64	-10000	0	-1.3	138	138
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.26	0.51	-10000	0	-0.93	145	145
COL1A1	-0.26	0.59	-10000	0	-1.4	90	90
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.39	0.69	-10000	0	-1.4	127	127
IL2R gamma/JAK3	0.054	0.035	-10000	0	-0.29	4	4
TFF3	-0.53	0.76	-10000	0	-1.4	193	193
ALOX15	-0.38	0.65	-10000	0	-1.3	133	133
MYBL1	-0.011	0.13	-10000	0	-0.42	43	43
T-helper 2 cell differentiation	-0.28	0.52	-10000	0	-0.98	143	143
SHC1	0.028	0.025	-10000	0	-0.42	1	1
CEBPB	0.029	0.056	-10000	0	-0.26	14	14
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.13	0.34	-10000	0	-0.75	59	59
mol:PI-3-4-5-P3	-0.12	0.33	-10000	0	-0.77	49	49
PI3K	-0.13	0.35	-10000	0	-0.84	49	49
DOK2	0.009	0.086	-10000	0	-0.42	19	19
ETS1	0.015	0.043	-10000	0	-0.38	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.062	0.25	-10000	0	-0.62	30	30
ITGB3	-0.37	0.65	-10000	0	-1.3	135	135
PIGR	-0.46	0.77	-10000	0	-1.4	170	170
IGHE	0.011	0.088	0.18	57	-0.22	10	67
MAPKKK cascade	-0.06	0.24	-10000	0	-0.61	30	30
BCL6	0.018	0.085	-10000	0	-0.42	18	18
OPRM1	-0.37	0.64	-10000	0	-1.3	131	131
RETNLB	-0.37	0.64	-10000	0	-1.3	134	134
SELP	-0.43	0.75	-10000	0	-1.4	158	158
AICDA	-0.36	0.62	-10000	0	-1.3	128	128

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.007	0.13	-10000	0	-0.22	134	134
ER alpha/Gai/GDP/Gbeta gamma	-0.12	0.21	-10000	0	-0.36	160	160
AKT1	-0.22	0.37	-10000	0	-0.74	167	167
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.22	0.38	-10000	0	-0.75	167	167
mol:Ca2+	-0.071	0.15	-10000	0	-0.42	60	60
IGF1R	-0.042	0.17	-10000	0	-0.42	84	84
E2/ER alpha (dimer)/Striatin	-0.037	0.13	-10000	0	-0.25	135	135
SHC1	0.028	0.025	-10000	0	-0.42	1	1
apoptosis	0.21	0.35	0.7	167	-10000	0	167
RhoA/GTP	-0.038	0.11	-10000	0	-0.21	127	127
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.1	0.2	-10000	0	-0.38	151	151
regulation of stress fiber formation	0.038	0.1	0.31	8	-0.26	3	11
E2/ERA-ERB (dimer)	-0.037	0.13	-10000	0	-0.25	132	132
KRAS	0.028	0.054	-10000	0	-0.42	7	7
G13/GTP	-0.032	0.12	-10000	0	-0.23	123	123
pseudopodium formation	-0.038	0.1	0.26	3	-0.31	8	11
E2/ER alpha (dimer)/PELP1	-0.038	0.13	-10000	0	-0.25	131	131
GRB2	0.033	0.011	-10000	0	-10000	0	0
GNG2	0.034	0.021	-10000	0	-0.42	1	1
GNAO1	0.03	0.014	-10000	0	-10000	0	0
HRAS	0.032	0.036	-10000	0	-0.42	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.14	0.23	-10000	0	-0.44	164	164
E2/ER beta (dimer)	0.026	0.005	-10000	0	-10000	0	0
mol:GDP	-0.075	0.17	-10000	0	-0.33	137	137
mol:NADP	-0.14	0.23	-10000	0	-0.44	164	164
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
mol:IP3	-0.072	0.15	-10000	0	-0.4	69	69
IGF-1R heterotetramer	-0.042	0.17	-10000	0	-0.42	84	84
PLCB1	-0.072	0.16	-10000	0	-0.36	91	91
PLCB2	-0.051	0.15	-10000	0	-0.42	57	57
IGF1	-0.038	0.16	-10000	0	-0.42	78	78
mol:L-citrulline	-0.14	0.23	-10000	0	-0.44	164	164
RHOA	0.026	0.061	-10000	0	-0.42	9	9
Gai/GDP	-0.099	0.27	-10000	0	-0.62	102	102
JNK cascade	0.026	0.005	-10000	0	-10000	0	0
BCAR1	0.03	0.014	-10000	0	-10000	0	0
ESR2	0.035	0.007	-10000	0	-10000	0	0
GNAQ	0	0	-10000	0	-10000	0	0
ESR1	-0.089	0.2	-10000	0	-0.42	132	132
Gq family/GDP/Gbeta gamma	-0.015	0.17	-10000	0	-0.69	22	22
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.034	0.13	-10000	0	-0.57	7	7
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.089	0.19	0.27	1	-0.38	122	123
GNAZ	0.023	0.07	-10000	0	-0.42	12	12
E2/ER alpha (dimer)	-0.062	0.14	-10000	0	-0.3	132	132
STRN	0.031	0.045	-10000	0	-0.42	5	5
GNAL	0.031	0.036	-10000	0	-0.42	3	3
PELP1	0.033	0.011	-10000	0	-10000	0	0
MAPK11	0.016	0.006	-10000	0	-10000	0	0
GNAI2	0.028	0.054	-10000	0	-0.42	7	7
GNAI3	0.035	0.006	-10000	0	-10000	0	0
GNAI1	0.017	0.087	-10000	0	-0.42	19	19
HBEGF	-0.11	0.2	0.32	5	-0.48	64	69
cAMP biosynthetic process	-0.028	0.1	-10000	0	-0.2	129	129
SRC	-0.11	0.2	0.25	1	-0.36	141	142
PI3K	0.036	0.065	-10000	0	-0.3	17	17
GNB1	0.032	0.045	-10000	0	-0.42	5	5
G13/GDP/Gbeta gamma	-0.049	0.16	-10000	0	-0.32	114	114
SOS1	0.035	0.021	-10000	0	-0.42	1	1
IGF-1R heterotetramer/IGF1	-0.13	0.19	-10000	0	-0.4	147	147
Gs family/GTP	-0.022	0.11	-10000	0	-0.21	129	129
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.053	0.054	-10000	0	-0.23	15	15
vasodilation	-0.13	0.22	-10000	0	-0.42	164	164
mol:DAG	-0.072	0.15	-10000	0	-0.4	69	69
Gs family/GDP/Gbeta gamma	-0.064	0.15	-10000	0	-0.32	110	110
MSN	-0.042	0.11	0.31	2	-0.33	8	10
Gq family/GTP	-0.052	0.15	-10000	0	-0.43	59	59
mol:PI-3-4-5-P3	-0.21	0.36	-10000	0	-0.72	167	167
NRAS	0.029	0.054	-10000	0	-0.42	7	7
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.13	0.22	0.42	164	-10000	0	164
GRB2/SOS1	0.048	0.023	-10000	0	-0.3	1	1
RhoA/GDP	-0.061	0.17	-10000	0	-0.32	140	140
NOS3	-0.14	0.24	-10000	0	-0.47	164	164
GNA11	0.033	0.036	-10000	0	-0.42	3	3
MAPKKK cascade	-0.15	0.26	-10000	0	-0.52	159	159
E2/ER alpha (dimer)/PELP1/Src	-0.11	0.21	0.28	1	-0.39	152	153
ruffle organization	-0.038	0.1	0.26	3	-0.31	8	11
ROCK2	-0.039	0.12	0.33	2	-0.33	10	12
GNA14	-0.009	0.13	-10000	0	-0.42	43	43
GNA15	0.03	0.046	-10000	0	-0.42	5	5
GNA13	0.029	0.037	-10000	0	-0.42	3	3
MMP9	-0.12	0.2	0.35	7	-0.47	66	73
MMP2	-0.11	0.19	0.27	3	-0.46	64	67

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.032	0.036	-10000	0	-0.42	3	3
EGFR	-0.015	0.13	-10000	0	-0.42	49	49
EGF/EGFR	-0.072	0.18	-10000	0	-0.27	199	199
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.001	0.13	-10000	0	-0.23	104	104
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	-0.002	0.12	-10000	0	-0.42	41	41
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	-0.069	0.19	-10000	0	-0.42	110	110
EGF/EGFR dimer/SHC	-0.029	0.14	-10000	0	-0.26	120	120
mol:GDP	-0.005	0.12	-10000	0	-0.23	104	104
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	-0.038	0.16	-10000	0	-0.42	77	77
GRB2/SOS1	0.048	0.023	-10000	0	-0.3	1	1
HRAS/GTP	-0.017	0.11	-10000	0	-0.21	106	106
SHC1	0.028	0.025	-10000	0	-0.42	1	1
HRAS/GDP	-0.007	0.12	-10000	0	-0.22	106	106
FRAP1	-0.017	0.14	0.38	10	-0.23	74	84
EGF/EGFR dimer	-0.061	0.16	-10000	0	-0.3	152	152
SOS1	0.035	0.021	-10000	0	-0.42	1	1
GRB2	0.033	0.011	-10000	0	-10000	0	0
ETA receptor/Endothelin-1	-0.029	0.16	-10000	0	-0.33	103	103

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.034	0.034	-10000	0	-0.26	4	4
NFATC2	-0.052	0.21	-10000	0	-0.51	51	51
NFATC3	-0.018	0.12	-10000	0	-0.26	69	69
CD40LG	-0.19	0.38	-10000	0	-0.76	131	131
ITCH	0.013	0.071	-10000	0	-0.22	42	42
CBLB	0.014	0.07	-10000	0	-0.22	41	41
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.14	0.33	-10000	0	-0.82	68	68
JUNB	0.032	0.041	-10000	0	-0.42	4	4
CaM/Ca2+/Calcineurin A alpha-beta B1	0.022	0.087	-10000	0	-0.26	44	44
T cell anergy	-0.016	0.12	0.26	2	-0.36	45	47
TLE4	-0.045	0.17	-10000	0	-0.52	34	34
Jun/NFAT1-c-4/p21SNFT	-0.17	0.4	-10000	0	-0.79	123	123
AP-1/NFAT1-c-4	-0.19	0.46	-10000	0	-0.85	131	131
IKZF1	-0.039	0.14	-10000	0	-0.36	48	48
T-helper 2 cell differentiation	-0.17	0.3	-10000	0	-0.8	66	66
AP-1/NFAT1	-0.045	0.2	-10000	0	-0.41	79	79
CALM1	0.028	0.058	-10000	0	-0.16	42	42
EGR2	-0.23	0.49	-10000	0	-1.1	89	89
EGR3	-0.29	0.55	-10000	0	-1.1	131	131
NFAT1/FOXP3	-0.018	0.16	-10000	0	-0.39	43	43
EGR1	-0.038	0.16	-10000	0	-0.42	76	76
JUN	-0.003	0.12	-10000	0	-0.42	39	39
EGR4	0	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.005	0.046	-10000	0	-0.15	45	45
GBP3	-0.089	0.25	-10000	0	-0.61	79	79
FOSL1	0.035	0.007	-10000	0	-10000	0	0
NFAT1-c-4/MAF/IRF4	-0.16	0.4	-10000	0	-0.77	125	125
DGKA	-0.04	0.16	-10000	0	-0.44	39	39
CREM	0.034	0.007	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.18	0.41	-10000	0	-0.81	126	126
CTLA4	-0.027	0.14	-10000	0	-0.38	33	33
NFAT1-c-4 (dimer)/EGR1	-0.2	0.43	-10000	0	-0.84	135	135
NFAT1-c-4 (dimer)/EGR4	-0.17	0.39	-10000	0	-0.78	127	127
FOS	-0.034	0.15	-10000	0	-0.42	66	66
IFNG	-0.19	0.43	-10000	0	-1.1	75	75
T cell activation	-0.1	0.26	-10000	0	-0.78	29	29
MAF	0.015	0.078	-10000	0	-0.42	15	15
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.15	0.34	0.68	122	-10000	0	122
TNF	-0.2	0.38	-10000	0	-0.76	136	136
FASLG	-0.35	0.65	-10000	0	-1.2	156	156
TBX21	-0.044	0.17	-10000	0	-0.43	84	84
BATF3	0	0.001	-10000	0	-10000	0	0
PRKCQ	0.021	0.061	-10000	0	-0.32	11	11
PTPN1	-0.038	0.15	-10000	0	-0.41	39	39
NFAT1-c-4/ICER1	-0.17	0.4	-10000	0	-0.78	126	126
GATA3	-0.047	0.18	-10000	0	-0.42	91	91
T-helper 1 cell differentiation	-0.19	0.41	-10000	0	-1	75	75
IL2RA	-0.14	0.33	-10000	0	-0.78	74	74
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.035	0.14	-10000	0	-0.39	36	36
E2F1	0.033	0.054	-10000	0	-0.42	7	7
PPARG	0.012	0.093	-10000	0	-0.42	22	22
SLC3A2	-0.035	0.14	-10000	0	-0.38	41	41
IRF4	0.031	0.031	-10000	0	-0.42	2	2
PTGS2	-0.18	0.36	-10000	0	-0.77	111	111
CSF2	-0.19	0.38	-10000	0	-0.75	132	132
JunB/Fra1/NFAT1-c-4	-0.15	0.39	-10000	0	-0.77	124	124
IL4	-0.18	0.32	-10000	0	-0.85	63	63
IL5	-0.19	0.38	-10000	0	-0.75	133	133
IL2	-0.1	0.27	-10000	0	-0.82	26	26
IL3	-0.013	0.14	-10000	0	-0.85	10	10
RNF128	-0.016	0.16	-10000	0	-0.52	44	44
NFATC1	-0.15	0.34	-10000	0	-0.68	121	121
CDK4	0.1	0.22	0.59	27	-10000	0	27
PTPRK	-0.069	0.22	-10000	0	-0.64	55	55
IL8	-0.2	0.39	-10000	0	-0.77	131	131
POU2F1	0.034	0.017	-10000	0	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.035	0.021	-10000	0	-0.42	1	1
CCL5	-0.014	0.14	-10000	0	-0.42	52	52
SDCBP	0.023	0.058	-10000	0	-0.42	8	8
FGFR/FGF2/Syndecan-1	-0.11	0.23	0.22	6	-0.53	91	97
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	-0.11	0.22	-10000	0	-0.5	91	91
Syndecan-1/Syntenin	-0.1	0.22	0.26	1	-0.49	92	93
MAPK3	-0.097	0.2	0.24	1	-0.46	89	90
HGF/MET	0.042	0.055	-10000	0	-0.3	12	12
TGFB1/TGF beta receptor Type II	0.035	0.021	-10000	0	-0.42	1	1
BSG	0.035	0.008	-10000	0	-10000	0	0
keratinocyte migration	-0.11	0.22	-10000	0	-0.49	91	91
Syndecan-1/RANTES	-0.13	0.24	0.26	1	-0.5	113	114
Syndecan-1/CD147	-0.096	0.23	0.27	1	-0.49	93	94
Syndecan-1/Syntenin/PIP2	-0.1	0.21	0.25	1	-0.47	92	93
LAMA5	0.027	0.05	-10000	0	-0.42	6	6
positive regulation of cell-cell adhesion	-0.099	0.2	0.24	1	-0.46	92	93
MMP7	-0.032	0.15	-10000	0	-0.42	68	68
HGF	0.028	0.057	-10000	0	-0.42	8	8
Syndecan-1/CASK	-0.12	0.21	-10000	0	-0.5	95	95
Syndecan-1/HGF/MET	-0.1	0.23	0.27	1	-0.49	96	97
regulation of cell adhesion	-0.1	0.19	0.23	1	-0.45	87	88
HPSE	0.015	0.091	-10000	0	-0.42	21	21
positive regulation of cell migration	-0.11	0.23	0.22	6	-0.53	91	97
SDC1	-0.11	0.23	0.28	1	-0.53	91	92
Syndecan-1/Collagen	-0.11	0.23	0.22	6	-0.53	91	97
PPIB	0.033	0.03	-10000	0	-0.42	2	2
MET	0.03	0.041	-10000	0	-0.42	4	4
PRKACA	0.036	0.005	-10000	0	-10000	0	0
MMP9	-0.013	0.14	-10000	0	-0.42	52	52
MAPK1	-0.1	0.21	0.24	1	-0.46	93	94
homophilic cell adhesion	-0.12	0.22	0.22	6	-0.52	92	98
MMP1	-0.074	0.18	-10000	0	-0.42	107	107

×

Glucocorticoid receptor regulatory network

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
PCK2	0.054	0.15	0.31	10	-0.83	8	18
SMARCC2	0.036	0.005	-10000	0	-10000	0	0
SMARCC1	0.033	0.03	-10000	0	-0.42	2	2
TBX21	-0.15	0.28	0.36	1	-0.71	92	93
SUMO2	0.029	0.02	-10000	0	-10000	0	0
STAT1 (dimer)	0.021	0.091	-10000	0	-0.38	23	23
FKBP4	0.03	0.046	-10000	0	-0.42	5	5
FKBP5	-0.003	0.12	-10000	0	-0.42	41	41
GR alpha/HSP90/FKBP51/HSP90	0.061	0.14	0.25	113	-0.25	26	139
PRL	-0.035	0.13	-10000	0	-0.96	2	2
cortisol/GR alpha (dimer)/TIF2	0.14	0.24	0.52	114	-0.38	2	116
RELA	-0.02	0.11	-10000	0	-0.19	113	113
FGG	0.14	0.23	0.45	139	-0.38	3	142
GR beta/TIF2	0.07	0.14	0.28	100	-0.3	9	109
IFNG	-0.26	0.41	-10000	0	-0.87	122	122
apoptosis	-0.003	0.17	0.51	4	-0.51	10	14
CREB1	0.038	0.042	-10000	0	-0.37	5	5
histone acetylation	-0.025	0.11	0.31	4	-0.32	34	38
BGLAP	-0.047	0.14	-10000	0	-0.5	14	14
GR/PKAc	0.11	0.12	0.32	56	-0.26	14	70
NF kappa B1 p50/RelA	-0.039	0.19	-10000	0	-0.32	132	132
SMARCD1	0.036	0.004	-10000	0	-10000	0	0
MDM2	0.072	0.1	0.24	108	-10000	0	108
GATA3	-0.039	0.18	-10000	0	-0.41	91	91
AKT1	0.03	0.036	0.19	8	-0.43	2	10
CSF2	-0.05	0.13	-10000	0	-0.86	5	5
GSK3B	0.03	0.02	-10000	0	-10000	0	0
NR1I3	0.029	0.18	0.54	5	-0.67	6	11
CSN2	0.12	0.19	0.38	137	-0.36	6	143
BRG1/BAF155/BAF170/BAF60A	0.083	0.037	-10000	0	-0.23	3	3
NFATC1	0.023	0.09	-10000	0	-0.4	21	21
POU2F1	0.033	0.021	-10000	0	-0.25	1	1
CDKN1A	-0.047	0.26	-10000	0	-1.5	14	14
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.001	0.006	-10000	0	-10000	0	0
SFN	0.012	0.099	-10000	0	-0.42	25	25
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.07	0.14	0.29	60	-0.23	42	102
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.079	0.31	0.46	4	-0.78	78	82
JUN	-0.15	0.23	0.37	4	-0.47	138	142
IL4	-0.087	0.19	-10000	0	-0.59	32	32
CDK5R1	0.033	0.01	-10000	0	-10000	0	0
PRKACA	0.036	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.097	0.21	0.21	69	-0.38	139	208
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.086	0.13	0.29	68	-0.23	31	99
cortisol/GR alpha (monomer)	0.19	0.31	0.6	151	-0.41	4	155
NCOA2	0.025	0.047	-10000	0	-0.42	5	5
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.081	0.16	-10000	0	-0.41	79	79
AP-1/NFAT1-c-4	-0.27	0.37	-10000	0	-0.74	160	160
AFP	-0.12	0.19	-10000	0	-0.71	13	13
SUV420H1	0.033	0.022	-10000	0	-0.42	1	1
IRF1	0.095	0.21	0.41	67	-0.71	13	80
TP53	0.014	0.13	-10000	0	-0.46	32	32
PPP5C	0.032	0.041	-10000	0	-0.42	4	4
KRT17	-0.38	0.56	-10000	0	-1.2	146	146
KRT14	-0.26	0.49	-10000	0	-1.2	97	97
TBP	0.04	0.019	-10000	0	-0.28	1	1
CREBBP	0.066	0.096	0.28	80	-10000	0	80
HDAC1	0.03	0.021	-10000	0	-0.42	1	1
HDAC2	0.031	0.023	-10000	0	-0.42	1	1
AP-1	-0.27	0.38	-10000	0	-0.75	161	161
MAPK14	0.033	0.014	-10000	0	-10000	0	0
MAPK10	0.009	0.089	-10000	0	-0.42	20	20
MAPK11	0.028	0.02	-10000	0	-10000	0	0
KRT5	-0.39	0.57	-10000	0	-1.2	150	150
interleukin-1 receptor activity	-0.001	0.007	-10000	0	-10000	0	0
NCOA1	0.032	0.048	-10000	0	-0.37	6	6
STAT1	0.021	0.091	-10000	0	-0.38	23	23
CGA	-0.071	0.17	-10000	0	-0.55	29	29
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.081	0.16	0.36	93	-0.39	2	95
MAPK3	0.027	0.028	-10000	0	-0.42	1	1
MAPK1	0.03	0.025	-10000	0	-0.42	1	1
ICAM1	-0.16	0.3	0.33	1	-0.64	107	108
NFKB1	-0.021	0.11	-10000	0	-0.2	100	100
MAPK8	-0.11	0.2	0.56	2	-0.38	130	132
MAPK9	0.016	0.085	-10000	0	-0.42	18	18
cortisol/GR alpha (dimer)	-0.005	0.18	0.52	4	-0.53	10	14
BAX	-0.01	0.1	-10000	0	-10000	0	0
POMC	-0.091	0.2	0.62	1	-1.2	5	6
EP300	0.066	0.099	0.28	84	-0.43	2	86
cortisol/GR alpha (dimer)/p53	0.12	0.25	0.52	110	-0.39	2	112
proteasomal ubiquitin-dependent protein catabolic process	0.053	0.11	0.26	76	-10000	0	76
SGK1	0.08	0.14	0.33	94	-0.33	4	98
IL13	-0.22	0.26	-10000	0	-0.63	99	99
IL6	-0.2	0.38	-10000	0	-0.87	98	98
PRKACG	0.034	0.029	-10000	0	-0.42	2	2
IL5	-0.18	0.22	-10000	0	-0.57	69	69
IL2	-0.22	0.33	-10000	0	-0.74	113	113
CDK5	0.034	0.008	-10000	0	-10000	0	0
PRKACB	0.008	0.099	-10000	0	-0.42	25	25
HSP90AA1	0	0	-10000	0	-10000	0	0
IL8	-0.18	0.34	-10000	0	-0.82	91	91
CDK5R1/CDK5	0.047	0.018	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.001	0.18	-10000	0	-0.34	64	64
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.16	0.24	0.48	147	-0.35	2	149
SMARCA4	0.035	0.021	-10000	0	-0.42	1	1
chromatin remodeling	0.11	0.16	0.34	130	-10000	0	130
NF kappa B1 p50/RelA/Cbp	0.026	0.18	0.35	40	-0.3	58	98
JUN (dimer)	-0.15	0.23	0.37	4	-0.47	137	141
YWHAH	0.031	0.036	-10000	0	-0.42	3	3
VIPR1	-0.1	0.21	-10000	0	-0.48	89	89
NR3C1	0.12	0.21	0.39	142	-0.41	8	150
NR4A1	0.037	0.045	-10000	0	-0.44	4	4
TIF2/SUV420H1	0.037	0.046	-10000	0	-0.35	5	5
MAPKKK cascade	-0.003	0.17	0.51	4	-0.51	10	14
cortisol/GR alpha (dimer)/Src-1	0.18	0.26	0.52	151	-0.34	2	153
PBX1	0.02	0.077	-10000	0	-0.4	15	15
POU1F1	0.04	0.025	-10000	0	-0.33	2	2
SELE	-0.23	0.42	-10000	0	-0.93	124	124
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.11	0.16	0.34	129	-10000	0	129
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.16	0.24	0.48	147	-0.35	2	149
mol:cortisol	0.11	0.18	0.35	150	-10000	0	150
MMP1	-0.37	0.54	-10000	0	-1.2	155	155

×

HIF-1-alpha transcription factor network

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
PKM2	-0.055	0.35	-10000	0	-0.72	76	76
HDAC7	0	0.003	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.008	0.35	-10000	0	-0.71	57	57
SMAD4	0.029	0.054	-10000	0	-0.42	7	7
ID2	-0.056	0.36	-10000	0	-0.72	76	76
AP1	-0.033	0.16	-10000	0	-0.35	88	88
ABCG2	-0.057	0.36	-10000	0	-0.73	77	77
HIF1A	-0.023	0.16	-10000	0	-0.48	46	46
TFF3	-0.1	0.37	-10000	0	-0.74	88	88
GATA2	0.018	0.054	-10000	0	-0.42	5	5
AKT1	0.012	0.09	-10000	0	-0.31	6	6
response to hypoxia	-0.007	0.066	-10000	0	-0.14	32	32
MCL1	-0.058	0.35	-10000	0	-0.72	76	76
NDRG1	-0.065	0.33	-10000	0	-0.74	66	66
SERPINE1	-0.063	0.36	-10000	0	-0.73	79	79
FECH	-0.062	0.36	-10000	0	-0.72	79	79
FURIN	-0.057	0.35	-10000	0	-0.72	77	77
NCOA2	0.026	0.047	-10000	0	-0.42	5	5
EP300	0.008	0.11	-10000	0	-0.3	27	27
HMOX1	-0.066	0.36	-10000	0	-0.73	80	80
BHLHE40	-0.077	0.34	-10000	0	-0.71	77	77
BHLHE41	-0.077	0.34	-10000	0	-0.71	77	77
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.05	0.17	-10000	0	-0.33	45	45
ENG	-0.007	0.13	0.27	1	-0.31	43	44
JUN	-0.009	0.12	-10000	0	-0.43	39	39
RORA	-0.064	0.36	-10000	0	-0.73	77	77
ABCB1	-0.029	0.24	-10000	0	-0.94	28	28
TFRC	-0.072	0.36	-10000	0	-0.73	83	83
CXCR4	-0.067	0.37	-10000	0	-0.74	83	83
TF	-0.056	0.35	-10000	0	-0.72	75	75
CITED2	-0.059	0.35	-10000	0	-0.74	72	72
HIF1A/ARNT	-0.035	0.43	-10000	0	-0.88	60	60
LDHA	0.01	0.19	-10000	0	-0.91	15	15
ETS1	-0.065	0.35	-10000	0	-0.72	76	76
PGK1	-0.053	0.36	-10000	0	-0.72	76	76
NOS2	-0.077	0.34	-10000	0	-0.71	77	77
ITGB2	-0.064	0.36	-10000	0	-0.74	79	79
ALDOA	-0.05	0.35	-10000	0	-0.74	70	70
Cbp/p300/CITED2	-0.057	0.36	-10000	0	-0.8	62	62
FOS	-0.038	0.15	-10000	0	-0.42	66	66
HK2	-0.054	0.36	-10000	0	-0.72	76	76
SP1	0.035	0.039	-10000	0	-0.19	7	7
GCK	0.013	0.18	-10000	0	-1.2	4	4
HK1	-0.053	0.35	-10000	0	-0.72	76	76
NPM1	-0.052	0.35	-10000	0	-0.73	73	73
EGLN1	-0.065	0.33	-10000	0	-0.72	71	71
CREB1	0.039	0.027	-10000	0	-0.42	1	1
PGM1	-0.059	0.35	-10000	0	-0.72	77	77
SMAD3	0.027	0.061	-10000	0	-0.42	9	9
EDN1	-0.18	0.48	-10000	0	-1.2	86	86
IGFBP1	-0.053	0.35	-10000	0	-0.72	75	75
VEGFA	-0.042	0.27	0.44	1	-0.59	63	64
HIF1A/JAB1	0.003	0.12	-10000	0	-0.34	43	43
CP	-0.12	0.38	-10000	0	-0.77	90	90
CXCL12	-0.071	0.38	-10000	0	-0.74	85	85
COPS5	0.027	0.043	-10000	0	-0.42	4	4
SMAD3/SMAD4	0.041	0.063	-10000	0	-0.3	16	16
BNIP3	-0.06	0.36	-10000	0	-0.73	77	77
EGLN3	-0.08	0.38	-10000	0	-0.77	81	81
CA9	-0.06	0.35	-10000	0	-0.72	76	76
TERT	-0.056	0.35	-10000	0	-0.72	75	75
ENO1	-0.056	0.35	-10000	0	-0.73	74	74
PFKL	-0.056	0.36	-10000	0	-0.72	76	76
NCOA1	0.032	0.045	-10000	0	-0.42	5	5
ADM	-0.08	0.38	-10000	0	-0.75	89	89
ARNT	0.015	0.078	-10000	0	-0.16	2	2
HNF4A	0.035	0.033	-10000	0	-0.22	6	6
ADFP	-0.064	0.37	-10000	0	-0.74	81	81
SLC2A1	-0.03	0.29	-10000	0	-0.6	60	60
LEP	-0.072	0.36	-10000	0	-0.73	79	79
HIF1A/ARNT/Cbp/p300	-0.022	0.35	-10000	0	-0.72	59	59
EPO	-0.027	0.28	-10000	0	-0.71	39	39
CREBBP	0.017	0.098	-10000	0	-0.28	18	18
HIF1A/ARNT/Cbp/p300/HDAC7	-0.021	0.34	-10000	0	-0.69	59	59
PFKFB3	-0.058	0.35	-10000	0	-0.74	73	73
NT5E	-0.059	0.36	-10000	0	-0.74	75	75

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.04	0.19	-10000	0	-0.58	53	53
IHH	0.017	0.088	-10000	0	-0.28	24	24
SHH Np/Cholesterol/GAS1	-0.027	0.11	-10000	0	-0.24	101	101
LRPAP1	0.035	0.007	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.027	0.1	0.23	101	-10000	0	101
SMO/beta Arrestin2	-0.022	0.17	-10000	0	-0.42	56	56
SMO	-0.038	0.16	-10000	0	-0.37	83	83
AKT1	-0.015	0.16	-10000	0	-0.54	29	29
ARRB2	0.033	0.011	-10000	0	-10000	0	0
BOC	0.014	0.093	-10000	0	-0.42	22	22
ADRBK1	0.034	0.01	-10000	0	-10000	0	0
heart looping	-0.034	0.16	-10000	0	-0.37	83	83
STIL	-0.006	0.14	0.2	77	-0.23	104	181
DHH N/PTCH2	0.052	0.011	-10000	0	-10000	0	0
DHH N/PTCH1	-0.001	0.12	-10000	0	-0.29	69	69
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
DHH	0.036	0.005	-10000	0	-10000	0	0
PTHLH	-0.064	0.25	-10000	0	-0.73	56	56
determination of left/right symmetry	-0.034	0.16	-10000	0	-0.37	83	83
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
skeletal system development	-0.063	0.25	-10000	0	-0.72	56	56
IHH N/Hhip	0.035	0.065	-10000	0	-0.29	12	12
DHH N/Hhip	0.049	0.029	-10000	0	-0.3	3	3
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.034	0.16	-10000	0	-0.37	83	83
pancreas development	0.032	0.036	-10000	0	-0.42	3	3
HHAT	-0.017	0.13	-10000	0	-0.42	50	50
PI3K	0.036	0.065	-10000	0	-0.3	17	17
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.03	0.16	-10000	0	-0.42	71	71
somite specification	-0.034	0.16	-10000	0	-0.37	83	83
SHH Np/Cholesterol/PTCH1	-0.031	0.11	-10000	0	-0.23	102	102
SHH Np/Cholesterol/PTCH2	0.003	0.074	-10000	0	-0.23	44	44
SHH Np/Cholesterol/Megalin	-0.055	0.14	-10000	0	-0.27	133	133
SHH	-0.016	0.09	-10000	0	-0.3	46	46
catabolic process	-0.025	0.12	-10000	0	-0.32	70	70
SMO/Vitamin D3	-0.019	0.15	0.2	34	-0.33	63	97
SHH Np/Cholesterol/Hhip	0.002	0.075	-10000	0	-0.23	45	45
LRP2	-0.096	0.2	-10000	0	-0.42	144	144
receptor-mediated endocytosis	-0.071	0.18	-10000	0	-0.36	98	98
SHH Np/Cholesterol/BOC	-0.007	0.085	-10000	0	-0.23	63	63
SHH Np/Cholesterol/CDO	-0.007	0.083	-10000	0	-0.24	56	56
mesenchymal cell differentiation	-0.001	0.074	0.23	45	-10000	0	45
mol:Vitamin D3	-0.007	0.13	0.2	62	-0.24	102	164
IHH N/PTCH2	0.037	0.06	-10000	0	-0.27	10	10
CDON	0.021	0.067	-10000	0	-0.42	11	11
IHH N/PTCH1	-0.005	0.13	-10000	0	-0.33	70	70
Megalin/LRPAP1	-0.049	0.16	-10000	0	-0.3	144	144
PTCH2	0.035	0.006	-10000	0	-10000	0	0
SHH Np/Cholesterol	-0.007	0.07	-10000	0	-0.23	46	46
PTCH1	-0.025	0.12	-10000	0	-0.32	70	70
HHIP	0.032	0.036	-10000	0	-0.42	3	3

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.017	0.085	-10000	0	-0.42	18	18
GNB1/GNG2	-0.05	0.08	-10000	0	-0.18	127	127
AKT1	-0.013	0.13	0.23	5	-0.24	47	52
EGF	-0.069	0.19	-10000	0	-0.42	110	110
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.016	0.063	0.25	5	-0.26	3	8
mol:Ca2+	-0.035	0.17	-10000	0	-0.3	132	132
LYN	0.015	0.057	0.26	4	-0.28	2	6
RhoA/GTP	-0.014	0.075	-10000	0	-0.13	111	111
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.055	0.19	-10000	0	-0.35	131	131
GNG2	0.034	0.021	-10000	0	-0.42	1	1
ARRB2	0.033	0.011	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.012	0.14	-10000	0	-0.46	32	32
G beta5/gamma2	-0.053	0.11	-10000	0	-0.24	124	124
PRKCH	-0.051	0.2	0.3	3	-0.36	129	132
DNM1	0.033	0.035	-10000	0	-0.42	3	3
TXA2/TP beta/beta Arrestin3	0.028	0.027	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	0.028	0.054	-10000	0	-0.42	7	7
G12 family/GTP	-0.048	0.16	-10000	0	-0.3	118	118
ADRBK1	0.034	0.01	-10000	0	-10000	0	0
ADRBK2	0.024	0.067	-10000	0	-0.42	11	11
RhoA/GTP/ROCK1	0.041	0.04	-10000	0	-0.25	8	8
mol:GDP	0.022	0.14	0.43	31	-0.23	2	33
mol:NADP	0.035	0.007	-10000	0	-10000	0	0
RAB11A	0.034	0.021	-10000	0	-0.42	1	1
PRKG1	0.035	0.006	-10000	0	-10000	0	0
mol:IP3	-0.052	0.21	-10000	0	-0.38	132	132
cell morphogenesis	0.04	0.039	-10000	0	-0.25	8	8
PLCB2	-0.086	0.27	-10000	0	-0.52	131	131
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.007	0.058	0.25	4	-0.24	4	8
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.01	0.075	0.25	5	-0.32	8	13
RHOA	0.026	0.061	-10000	0	-0.42	9	9
PTGIR	0.033	0.029	-10000	0	-0.42	2	2
PRKCB1	-0.055	0.21	-10000	0	-0.4	121	121
GNAQ	0	0	-10000	0	-10000	0	0
mol:L-citrulline	0.035	0.007	-10000	0	-10000	0	0
TXA2/TXA2-R family	-0.087	0.27	-10000	0	-0.52	131	131
LCK	-0.005	0.09	0.25	5	-0.31	12	17
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.049	0.047	0.23	1	-0.2	9	10
TXA2-R family/G12 family/GDP/G beta/gamma	0.036	0.093	-10000	0	-0.48	12	12
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.044	0.047	0.23	1	-0.2	9	10
MAPK14	-0.032	0.13	0.22	3	-0.24	127	130
TGM2/GTP	-0.062	0.23	-10000	0	-0.42	130	130
MAPK11	-0.034	0.13	0.25	3	-0.23	128	131
ARHGEF1	-0.011	0.11	0.24	4	-0.18	111	115
GNAI2	0.028	0.054	-10000	0	-0.42	7	7
JNK cascade	-0.054	0.21	-10000	0	-0.38	131	131
RAB11/GDP	0.034	0.021	-10000	0	-0.42	1	1
ICAM1	-0.036	0.16	-10000	0	-0.3	129	129
cAMP biosynthetic process	-0.049	0.19	-10000	0	-0.34	131	131
Gq family/GTP/EBP50	-0.021	0.096	-10000	0	-0.23	78	78
actin cytoskeleton reorganization	0.04	0.039	-10000	0	-0.25	8	8
SRC	0.015	0.064	0.25	5	-0.27	2	7
GNB5	0.025	0.067	-10000	0	-0.42	11	11
GNB1	0.032	0.045	-10000	0	-0.42	5	5
EGF/EGFR	-0.034	0.11	0.22	7	-0.3	37	44
VCAM1	-0.041	0.17	-10000	0	-0.31	129	129
TP beta/Gq family/GDP/G beta5/gamma2	-0.012	0.14	-10000	0	-0.46	32	32
platelet activation	-0.04	0.17	0.31	1	-0.3	130	131
PGI2/IP	0.025	0.021	-10000	0	-0.3	2	2
PRKACA	0.019	0.035	-10000	0	-0.23	9	9
Gq family/GDP/G beta5/gamma2	-0.007	0.12	-10000	0	-0.4	33	33
TXA2/TP beta/beta Arrestin2	0.009	0.066	-10000	0	-0.44	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.008	0.029	-10000	0	-0.21	8	8
mol:DAG	-0.064	0.23	-10000	0	-0.43	129	129
EGFR	-0.015	0.13	-10000	0	-0.42	49	49
TXA2/TP alpha	-0.074	0.25	-10000	0	-0.47	131	131
Gq family/GTP	-0.016	0.077	0.22	2	-0.22	57	59
YES1	0.014	0.068	0.25	5	-0.28	6	11
GNAI2/GTP	0.022	0.052	-10000	0	-0.21	16	16
PGD2/DP	0.02	0.038	-10000	0	-0.3	7	7
SLC9A3R1	-0.009	0.13	-10000	0	-0.42	46	46
FYN	0.011	0.067	0.25	4	-0.28	6	10
mol:NO	0.035	0.007	-10000	0	-10000	0	0
GNA15	0.03	0.046	-10000	0	-0.42	5	5
PGK/cGMP	0.046	0.012	-10000	0	-10000	0	0
RhoA/GDP	0.026	0.06	-10000	0	-0.41	9	9
TP alpha/TGM2/GDP/G beta/gamma	0.056	0.075	0.28	2	-0.22	22	24
NOS3	0.035	0.007	-10000	0	-10000	0	0
RAC1	0.035	0.006	-10000	0	-10000	0	0
PRKCA	-0.04	0.19	0.3	4	-0.35	114	118
PRKCB	-0.052	0.19	-10000	0	-0.36	130	130
PRKCE	-0.052	0.2	0.29	2	-0.36	128	130
PRKCD	-0.059	0.2	-10000	0	-0.39	128	128
PRKCG	-0.058	0.21	-10000	0	-0.39	130	130
muscle contraction	-0.081	0.25	-10000	0	-0.48	131	131
PRKCZ	-0.046	0.18	-10000	0	-0.34	131	131
ARR3	0.036	0.002	-10000	0	-10000	0	0
TXA2/TP beta	0.042	0.056	0.28	1	-0.21	11	12
PRKCQ	-0.048	0.2	0.3	2	-0.37	124	126
MAPKKK cascade	-0.07	0.24	-10000	0	-0.45	130	130
SELE	-0.055	0.19	-10000	0	-0.37	129	129
TP beta/GNAI2/GDP/G beta/gamma	0.062	0.067	0.28	2	-0.23	16	18
ROCK1	0.036	0.006	-10000	0	-10000	0	0
GNA14	-0.009	0.13	-10000	0	-0.42	43	43
chemotaxis	-0.11	0.31	-10000	0	-0.61	129	129
GNA12	0.035	0.007	-10000	0	-10000	0	0
GNA13	0.029	0.037	-10000	0	-0.42	3	3
GNA11	0.033	0.036	-10000	0	-0.42	3	3
Rac1/GTP	0.026	0.005	-10000	0	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.029	0.05	-10000	0	-0.42	6	6
LAT2	-0.049	0.14	-10000	0	-0.31	87	87
AP1	-0.06	0.21	-10000	0	-0.46	74	74
mol:PIP3	-0.025	0.19	0.3	20	-0.36	81	101
IKBKB	0.011	0.13	0.26	45	-0.24	44	89
AKT1	0.014	0.18	0.33	74	-0.37	24	98
IKBKG	-0.008	0.12	0.22	17	-0.24	47	64
MS4A2	-0.076	0.19	-10000	0	-0.41	120	120
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
MAP3K1	-0.04	0.16	0.25	7	-0.38	63	70
mol:Ca2+	-0.013	0.16	0.27	21	-0.28	77	98
LYN	0.032	0.017	-10000	0	-10000	0	0
CBLB	-0.047	0.14	-10000	0	-0.31	84	84
SHC1	0.028	0.025	-10000	0	-0.42	1	1
RasGAP/p62DOK	0.035	0.092	-10000	0	-0.24	46	46
positive regulation of cell migration	-0.005	0.063	-10000	0	-0.3	23	23
INPP5D	0	0	-10000	0	-10000	0	0
PLD2	-0.004	0.18	0.31	74	-0.3	61	135
PTPN13	-0.07	0.2	-10000	0	-0.56	42	42
PTPN11	0.033	0.024	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.004	0.15	0.33	16	-0.32	28	44
SYK	0.006	0.12	-10000	0	-0.42	34	34
GRB2	0.033	0.011	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.056	0.16	-10000	0	-0.36	87	87
LAT	-0.045	0.13	-10000	0	-0.3	82	82
PAK2	-0.035	0.17	0.26	8	-0.4	55	63
NFATC2	-0.012	0.066	-10000	0	-0.59	4	4
HRAS	-0.036	0.18	0.26	9	-0.42	58	67
GAB2	0.031	0.013	-10000	0	-10000	0	0
PLA2G1B	0.013	0.11	-10000	0	-0.94	5	5
Fc epsilon R1	-0.029	0.16	-10000	0	-0.3	109	109
Antigen/IgE/Fc epsilon R1	-0.024	0.14	-10000	0	-0.27	109	109
mol:GDP	-0.051	0.18	0.25	1	-0.47	54	55
JUN	-0.001	0.12	-10000	0	-0.42	39	39
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
FOS	-0.031	0.15	-10000	0	-0.42	66	66
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.044	0.14	-10000	0	-0.32	86	86
CHUK	-0.011	0.12	0.22	17	-0.24	50	67
KLRG1	-0.038	0.12	0.16	1	-0.28	76	77
VAV1	-0.051	0.14	-10000	0	-0.32	88	88
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.045	0.13	-10000	0	-0.31	80	80
negative regulation of mast cell degranulation	-0.041	0.11	-10000	0	-0.32	47	47
BTK	-0.057	0.18	-10000	0	-0.51	50	50
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.063	0.18	-10000	0	-0.35	115	115
GAB2/PI3K/SHP2	-0.052	0.1	-10000	0	-0.3	52	52
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.048	0.13	-10000	0	-0.26	108	108
RAF1	0.014	0.11	-10000	0	-1	5	5
Fc epsilon R1/FcgammaRIIB/SHIP	-0.024	0.16	-10000	0	-0.29	116	116
FCER1G	0.032	0.019	-10000	0	-10000	0	0
FCER1A	-0.023	0.14	-10000	0	-0.43	56	56
Antigen/IgE/Fc epsilon R1/Fyn	-0.016	0.14	-10000	0	-0.26	108	108
MAPK3	0.013	0.11	-10000	0	-0.97	5	5
MAPK1	0.008	0.11	-10000	0	-0.94	5	5
NFKB1	0.036	0.005	-10000	0	-10000	0	0
MAPK8	-0.041	0.22	-10000	0	-0.62	48	48
DUSP1	0.003	0.11	-10000	0	-0.42	34	34
NF-kappa-B/RelA	0.012	0.084	0.16	30	-0.15	41	71
actin cytoskeleton reorganization	-0.044	0.18	-10000	0	-0.53	32	32
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.028	0.18	0.26	1	-0.39	63	64
FER	-0.046	0.13	-10000	0	-0.31	83	83
RELA	0.035	0.006	-10000	0	-10000	0	0
ITK	-0.032	0.11	-10000	0	-0.39	40	40
SOS1	0.035	0.021	-10000	0	-0.42	1	1
PLCG1	-0.042	0.19	0.27	4	-0.46	55	59
cytokine secretion	-0.003	0.051	-10000	0	-0.13	13	13
SPHK1	-0.054	0.14	-10000	0	-0.32	85	85
PTK2	-0.046	0.19	-10000	0	-0.57	30	30
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.057	0.17	-10000	0	-0.38	89	89
EDG1	-0.005	0.064	-10000	0	-0.3	23	23
mol:DAG	-0.03	0.19	0.29	14	-0.37	83	97
MAP2K2	0.008	0.11	-10000	0	-0.97	5	5
MAP2K1	0.01	0.11	-10000	0	-0.96	5	5
MAP2K7	0.035	0.021	-10000	0	-0.42	1	1
KLRG1/SHP2	-0.024	0.12	0.21	3	-0.36	34	37
MAP2K4	-0.098	0.36	-10000	0	-0.92	76	76
Fc epsilon R1/FcgammaRIIB	-0.026	0.17	-10000	0	-0.31	116	116
mol:Choline	-0.003	0.18	0.31	75	-0.3	61	136
SHC/Grb2/SOS1	-0.011	0.14	-10000	0	-0.3	72	72
FYN	0.027	0.054	-10000	0	-0.42	7	7
DOK1	0.027	0.061	-10000	0	-0.42	9	9
PXN	-0.045	0.18	-10000	0	-0.52	30	30
HCLS1	-0.05	0.14	-10000	0	-0.32	87	87
PRKCB	-0.016	0.15	0.25	18	-0.28	82	100
FCGR2B	0.001	0.11	-10000	0	-0.42	30	30
IGHE	0.001	0.008	-10000	0	-10000	0	0
KLRG1/SHIP	-0.042	0.12	-10000	0	-0.32	46	46
LCP2	0.024	0.067	-10000	0	-0.42	11	11
PLA2G4A	-0.052	0.14	-10000	0	-0.32	87	87
RASA1	0.029	0.05	-10000	0	-0.42	6	6
mol:Phosphatidic acid	-0.003	0.18	0.31	75	-0.3	61	136
IKK complex	0.01	0.11	0.23	43	-0.2	34	77
WIPF1	0	0	-10000	0	-10000	0	0

×

Wnt 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.067	0.15	-9999	-0.29	136	136
FZD6	-0.028	0.14	-9999	-0.42	60	60
WNT6	0.03	0.031	-9999	-0.42	2	2
WNT4	-0.019	0.14	-9999	-0.42	58	58
FZD3	0.007	0.095	-9999	-0.42	23	23
WNT5A	-0.025	0.15	-9999	-0.42	63	63
WNT11	0.027	0.032	-9999	-0.42	2	2

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.003	0.1	-10000	0	-0.32	20	20
TBX21	-0.26	0.57	-10000	0	-1.3	101	101
B2M	0.024	0.063	-10000	0	-0.42	9	9
TYK2	0.014	0.043	-10000	0	-10000	0	0
IL12RB1	0.013	0.043	-10000	0	-10000	0	0
GADD45B	-0.18	0.44	-10000	0	-1	87	87
IL12RB2	-0.01	0.1	-10000	0	-0.43	26	26
GADD45G	-0.17	0.43	-10000	0	-1	87	87
natural killer cell activation	-0.005	0.022	-10000	0	-0.039	122	122
RELB	0.029	0.05	-10000	0	-0.42	6	6
RELA	0.035	0.006	-10000	0	-10000	0	0
IL18	0	0.11	-10000	0	-0.42	32	32
IL2RA	0.004	0.11	-10000	0	-0.42	31	31
IFNG	-0.007	0.12	-10000	0	-0.42	38	38
STAT3 (dimer)	-0.14	0.37	-10000	0	-0.79	101	101
HLA-DRB5	0.016	0.077	-10000	0	-0.42	14	14
FASLG	-0.18	0.5	-10000	0	-1.1	89	89
NF kappa B2 p52/RelB	-0.16	0.44	-10000	0	-0.94	100	100
CD4	0.028	0.021	-10000	0	-10000	0	0
SOCS1	0.032	0.023	-10000	0	-0.42	1	1
EntrezGene:6955	-0.003	0.012	-10000	0	-0.028	79	79
CD3D	0.008	0.078	-10000	0	-0.43	14	14
CD3E	0.024	0.026	-10000	0	-10000	0	0
CD3G	-0.028	0.14	-10000	0	-0.43	54	54
IL12Rbeta2/JAK2	0.004	0.096	-10000	0	-0.33	26	26
CCL3	-0.17	0.43	-10000	0	-1	89	89
CCL4	-0.18	0.45	-10000	0	-1	90	90
HLA-A	0.017	0.086	-10000	0	-0.42	18	18
IL18/IL18R	-0.001	0.16	-10000	0	-0.34	84	84
NOS2	-0.18	0.43	-10000	0	-0.87	114	114
IL12/IL12R/TYK2/JAK2/SPHK2	-0.008	0.11	-10000	0	-0.34	20	20
IL1R1	-0.22	0.5	-10000	0	-1.1	102	102
IL4	0.034	0.052	-10000	0	-0.42	5	5
JAK2	0.011	0.051	-10000	0	-0.46	2	2
EntrezGene:6957	-0.003	0.012	-10000	0	-0.029	70	70
TCR/CD3/MHC I/CD8	-0.073	0.28	-10000	0	-0.74	54	54
RAB7A	-0.13	0.34	-10000	0	-0.74	104	104
lysosomal transport	-0.12	0.32	-10000	0	-0.69	104	104
FOS	-0.24	0.5	-10000	0	-1.1	111	111
STAT4 (dimer)	-0.15	0.42	-10000	0	-0.89	101	101
STAT5A (dimer)	-0.18	0.44	-10000	0	-0.96	100	100
GZMA	-0.17	0.42	-10000	0	-0.92	102	102
GZMB	-0.26	0.56	-10000	0	-1.3	107	107
HLX	0	0	-10000	0	-10000	0	0
LCK	-0.21	0.5	-10000	0	-1.1	105	105
TCR/CD3/MHC II/CD4	-0.058	0.17	-10000	0	-0.37	89	89
IL2/IL2R	0.043	0.11	-10000	0	-0.29	46	46
MAPK14	-0.18	0.44	-10000	0	-0.96	102	102
CCR5	-0.16	0.4	-10000	0	-0.82	113	113
IL1B	-0.021	0.13	-10000	0	-0.44	40	40
STAT6	-0.055	0.2	-10000	0	-0.6	34	34
STAT4	0.01	0.1	-10000	0	-0.42	27	27
STAT3	0.028	0.031	-10000	0	-0.42	2	2
STAT1	0.02	0.075	-10000	0	-0.42	14	14
NFKB1	0.036	0.005	-10000	0	-10000	0	0
NFKB2	0.035	0.021	-10000	0	-0.42	1	1
IL12B	0.01	0.063	-10000	0	-0.42	6	6
CD8A	0	0.008	-10000	0	-0.036	21	21
CD8B	-0.001	0.009	-10000	0	-0.043	21	21
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.003	0.1	0.32	20	-10000	0	20
IL2RB	0.011	0.097	-10000	0	-0.42	24	24
proteasomal ubiquitin-dependent protein catabolic process	-0.13	0.37	-10000	0	-0.79	101	101
IL2RG	0.031	0.041	-10000	0	-0.42	4	4
IL12	0.015	0.076	-10000	0	-0.33	10	10
STAT5A	0.027	0.037	-10000	0	-0.42	3	3
CD247	-0.002	0.011	-10000	0	-0.027	69	69
IL2	0.032	0.036	-10000	0	-0.42	3	3
SPHK2	0.035	0.007	-10000	0	-10000	0	0
FRAP1	0.035	0.007	-10000	0	-10000	0	0
IL12A	0.006	0.059	-10000	0	-0.42	5	5
IL12/IL12R/TYK2/JAK2	-0.21	0.53	-10000	0	-1.1	102	102
MAP2K3	-0.18	0.46	-10000	0	-0.99	103	103
RIPK2	0.028	0.015	-10000	0	-10000	0	0
MAP2K6	-0.18	0.45	-10000	0	-0.96	105	105
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.019	0.064	-10000	0	-0.42	9	9
IL18RAP	-0.021	0.15	-10000	0	-0.43	58	58
IL12Rbeta1/TYK2	0.027	0.056	-10000	0	-10000	0	0
EOMES	-0.048	0.28	-10000	0	-1.1	30	30
STAT1 (dimer)	-0.15	0.38	-10000	0	-0.8	106	106
T cell proliferation	-0.11	0.3	-10000	0	-0.62	108	108
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.016	0.091	-10000	0	-0.43	20	20
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.11	0.33	-10000	0	-0.67	110	110
ATF2	-0.16	0.4	-10000	0	-0.89	97	97

×

FAS signaling pathway (CD95)

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
SPTAN1	0.024	0.082	0.19	84	-0.19	6	90
RFC1	0.021	0.074	0.19	72	-0.19	5	77
PRKDC	0.044	0.1	0.21	120	-0.2	5	125
RIPK1	0.036	0.008	-10000	0	-10000	0	0
CASP7	-0.007	0.14	-10000	0	-0.68	18	18
FASLG/FAS/FADD/FAF1	0.003	0.091	0.2	37	-0.26	28	65
MAP2K4	-0.025	0.17	0.44	2	-0.44	46	48
mol:ceramide	-0.013	0.11	-10000	0	-0.36	34	34
GSN	0.019	0.086	0.19	78	-0.22	14	92
FASLG/FAS/FADD/FAF1/Caspase 8	0.006	0.11	0.23	3	-0.32	29	32
FAS	0.003	0.11	-10000	0	-0.42	29	29
BID	-0.017	0.053	0.26	12	-0.27	7	19
MAP3K1	-0.009	0.14	0.3	4	-0.47	22	26
MAP3K7	0.033	0.011	-10000	0	-10000	0	0
RB1	0.019	0.071	0.19	70	-0.2	5	75
CFLAR	0.032	0.046	-10000	0	-0.42	5	5
HGF/MET	0.016	0.12	-10000	0	-0.26	77	77
ARHGDIB	0.016	0.09	0.2	73	-0.23	17	90
FADD	0.025	0.021	-10000	0	-10000	0	0
actin filament polymerization	-0.018	0.087	0.22	16	-0.19	73	89
NFKB1	0.004	0.1	-10000	0	-0.63	8	8
MAPK8	-0.044	0.21	0.51	2	-0.5	68	70
DFFA	0.023	0.078	0.19	81	-0.19	6	87
DNA fragmentation during apoptosis	0.022	0.08	0.19	76	-0.19	6	82
FAS/FADD/MET	0.034	0.077	-10000	0	-0.26	27	27
CFLAR/RIP1	0.049	0.038	-10000	0	-0.3	5	5
FAIM3	0.015	0.078	-10000	0	-0.42	15	15
FAF1	0.028	0.03	-10000	0	-0.42	1	1
PARP1	0.028	0.098	0.22	84	-0.21	8	92
DFFB	0.022	0.08	0.19	80	-0.19	6	86
CHUK	-0.008	0.11	-10000	0	-0.58	10	10
FASLG	-0.011	0.12	-10000	0	-0.42	36	36
FAS/FADD	0.02	0.077	-10000	0	-0.3	23	23
HGF	0.028	0.057	-10000	0	-0.42	8	8
LMNA	0.024	0.1	0.34	26	-0.22	6	32
CASP6	0.02	0.081	0.19	79	-0.21	9	88
CASP10	0.03	0.02	-10000	0	-10000	0	0
CASP3	0.032	0.092	0.23	81	-0.22	6	87
PTPN13	-0.03	0.16	-10000	0	-0.42	72	72
CASP8	-0.013	0.057	0.33	13	-10000	0	13
IL6	-0.1	0.41	-10000	0	-1.2	63	63
MET	0.03	0.041	-10000	0	-0.42	4	4
ICAD/CAD	0.018	0.073	0.17	69	-10000	0	69
FASLG/FAS/FADD/FAF1/Caspase 10	-0.014	0.11	-10000	0	-0.36	34	34
activation of caspase activity by cytochrome c	-0.017	0.053	0.26	12	-0.27	7	19
PAK2	0.021	0.077	0.19	81	-0.19	9	90
BCL2	-0.056	0.18	-10000	0	-0.42	99	99

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.013	0.083	-10000	0	-0.21	68	68
epithelial cell differentiation	0.026	0.094	-10000	0	-0.22	57	57
CYFIP2	-0.006	0.13	-10000	0	-0.42	45	45
ENAH	-0.028	0.075	0.3	2	-0.31	8	10
EGFR	-0.015	0.13	-10000	0	-0.42	49	49
EPHA2	0.032	0.036	-10000	0	-0.42	3	3
MYO6	-0.036	0.077	0.18	7	-0.22	69	76
CTNNB1	0.025	0.067	-10000	0	-0.42	11	11
ABI1/Sra1/Nap1	0.041	0.09	-10000	0	-0.26	40	40
AQP5	-0.095	0.17	-10000	0	-0.45	83	83
CTNND1	0.034	0.022	-10000	0	-0.42	1	1
mol:PI-4-5-P2	-0.032	0.07	0.18	6	-0.21	58	64
regulation of calcium-dependent cell-cell adhesion	-0.032	0.069	0.18	5	-0.21	60	65
EGF	-0.069	0.19	-10000	0	-0.42	110	110
NCKAP1	0.035	0.021	-10000	0	-0.42	1	1
AQP3	-0.094	0.17	-10000	0	-0.45	84	84
cortical microtubule organization	0.026	0.094	-10000	0	-0.22	57	57
GO:0000145	-0.033	0.065	0.16	6	-0.2	58	64
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.031	0.097	-10000	0	-0.22	57	57
MLLT4	0.02	0.078	-10000	0	-0.42	15	15
ARF6/GDP	-0.041	0.067	-10000	0	-0.22	56	56
ARF6	0.034	0.029	-10000	0	-0.42	2	2
Ephrin A1/EPHA2/NCK1/GIT1	0.053	0.072	-10000	0	-0.23	20	20
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.026	0.093	0.18	1	-0.34	18	19
PVRL2	0.026	0.064	-10000	0	-0.42	10	10
ZYX	-0.034	0.074	0.18	8	-0.21	64	72
ARF6/GTP	0.059	0.077	-10000	0	-0.24	20	20
CDH1	-0.011	0.13	-10000	0	-0.42	45	45
EGFR/EGFR/EGF/EGF	-0.057	0.14	-10000	0	-0.22	191	191
RhoA/GDP	0.023	0.099	-10000	0	-0.22	64	64
actin cytoskeleton organization	-0.04	0.074	0.16	7	-0.21	70	77
IGF-1R heterotetramer	-0.042	0.17	-10000	0	-0.42	84	84
GIT1	0.034	0.022	-10000	0	-0.42	1	1
IGF1R	-0.042	0.17	-10000	0	-0.42	84	84
IGF1	-0.038	0.16	-10000	0	-0.42	78	78
DIAPH1	0.002	0.2	-10000	0	-0.56	51	51
Wnt receptor signaling pathway	-0.026	0.094	0.22	57	-10000	0	57
RHOA	0.026	0.061	-10000	0	-0.42	9	9
RhoA/GTP	-0.043	0.068	-10000	0	-0.22	60	60
CTNNA1	0.035	0.021	-10000	0	-0.42	1	1
VCL	-0.041	0.075	0.17	7	-0.22	70	77
EFNA1	0.014	0.08	-10000	0	-0.42	16	16
LPP	-0.038	0.071	0.17	8	-0.21	60	68
Ephrin A1/EPHA2	0.01	0.092	-10000	0	-0.22	57	57
SEC6/SEC8	-0.048	0.069	-10000	0	-0.21	75	75
MGAT3	-0.032	0.07	0.18	5	-0.21	60	65
HGF/MET	0.016	0.093	-10000	0	-0.21	66	66
HGF	0.028	0.057	-10000	0	-0.42	8	8
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.013	0.084	-10000	0	-0.22	68	68
actin cable formation	0.016	0.11	0.26	12	-0.29	10	22
KIAA1543	-0.037	0.07	0.17	1	-0.22	54	55
KIFC3	-0.031	0.068	0.18	6	-0.21	52	58
NCK1	0.034	0.021	-10000	0	-0.42	1	1
EXOC3	0.036	0.002	-10000	0	-10000	0	0
ACTN1	-0.034	0.075	0.18	8	-0.21	65	73
NCK1/GIT1	0.049	0.025	-10000	0	-0.29	2	2
mol:GDP	0.026	0.094	-10000	0	-0.22	57	57
EXOC4	0.034	0.021	-10000	0	-0.42	1	1
STX4	-0.034	0.062	-10000	0	-0.21	57	57
PIP5K1C	-0.032	0.071	0.18	6	-0.21	58	64
LIMA1	0	0	-10000	0	-10000	0	0
ABI1	0.035	0.008	-10000	0	-10000	0	0
ROCK1	-0.009	0.1	0.3	5	-0.32	7	12
adherens junction assembly	-0.044	0.12	0.27	1	-0.48	15	16
IGF-1R heterotetramer/IGF1	-0.055	0.15	-10000	0	-0.24	175	175
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.032	0.076	-10000	0	-0.3	24	24
MET	0.03	0.041	-10000	0	-0.42	4	4
PLEKHA7	-0.031	0.07	0.18	8	-0.21	58	66
mol:GTP	0.051	0.071	-10000	0	-0.23	20	20
establishment of epithelial cell apical/basal polarity	-0.044	0.072	0.14	13	-0.2	64	77
cortical actin cytoskeleton stabilization	-0.013	0.083	-10000	0	-0.21	68	68
regulation of cell-cell adhesion	-0.04	0.074	0.16	7	-0.21	70	77
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.013	0.084	-10000	0	-0.22	68	68

×

IL23-mediated signaling events

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
CCL2	-0.16	0.54	-10000	0	-1.3	78	78
IL23A	-0.13	0.49	-10000	0	-1.1	71	71
NF kappa B1 p50/RelA/I kappa B alpha	-0.099	0.48	-10000	0	-1.1	71	71
positive regulation of T cell mediated cytotoxicity	-0.14	0.52	-10000	0	-1.2	68	68
ITGA3	-0.13	0.48	-10000	0	-1.1	73	73
IL17F	-0.049	0.33	0.47	5	-0.69	70	75
IL12B	0.02	0.075	-10000	0	-0.44	6	6
STAT1 (dimer)	-0.14	0.5	-10000	0	-1.2	69	69
CD4	-0.1	0.45	-10000	0	-1.1	63	63
IL23	-0.12	0.47	-10000	0	-1.1	70	70
IL23R	-0.001	0.22	-10000	0	-1.3	11	11
IL1B	-0.15	0.53	-10000	0	-1.3	74	74
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.077	0.46	-10000	0	-1.1	57	57
TYK2	0.02	0.046	-10000	0	-10000	0	0
STAT4	0.01	0.1	-10000	0	-0.42	27	27
STAT3	0.029	0.032	-10000	0	-0.42	2	2
IL18RAP	-0.022	0.15	-10000	0	-0.42	58	58
IL12RB1	0.02	0.046	-10000	0	-10000	0	0
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
IL12Rbeta1/TYK2	0.031	0.059	-10000	0	-10000	0	0
IL23R/JAK2	0.012	0.22	-10000	0	-1.2	11	11
positive regulation of chronic inflammatory response	-0.14	0.52	-10000	0	-1.2	68	68
natural killer cell activation	0	0.012	0.081	7	-10000	0	7
JAK2	0.023	0.063	-10000	0	-0.46	2	2
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
NFKB1	0.036	0.007	-10000	0	-10000	0	0
RELA	0.036	0.007	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.11	0.45	-10000	0	-1	70	70
ALOX12B	-0.11	0.45	-10000	0	-1.1	66	66
CXCL1	-0.17	0.55	-10000	0	-1.2	101	101
T cell proliferation	-0.14	0.52	-10000	0	-1.2	68	68
NFKBIA	0.034	0.03	-10000	0	-0.42	2	2
IL17A	-0.027	0.26	-10000	0	-0.53	70	70
PI3K	-0.12	0.49	-10000	0	-1.1	71	71
IFNG	-0.006	0.05	0.14	6	-0.13	45	51
STAT3 (dimer)	-0.12	0.46	-10000	0	-1.1	70	70
IL18R1	0.015	0.09	-10000	0	-0.42	20	20
IL23/IL23R/JAK2/TYK2/SOCS3	-0.035	0.29	0.51	1	-0.67	46	47
IL18/IL18R	-0.009	0.16	-10000	0	-0.34	84	84
macrophage activation	-0.006	0.021	-10000	0	-0.044	63	63
TNF	-0.13	0.48	-10000	0	-1.1	72	72
STAT3/STAT4	-0.13	0.49	-10000	0	-1.2	71	71
STAT4 (dimer)	-0.14	0.52	-10000	0	-1.2	71	71
IL18	-0.001	0.11	-10000	0	-0.42	32	32
IL19	-0.077	0.46	-10000	0	-1.1	58	58
STAT5A (dimer)	-0.14	0.49	-10000	0	-1.2	68	68
STAT1	0.02	0.075	-10000	0	-0.42	14	14
SOCS3	0.028	0.046	-10000	0	-0.42	5	5
CXCL9	-0.2	0.58	-10000	0	-1.2	109	109
MPO	-0.097	0.45	-10000	0	-1.1	62	62
positive regulation of humoral immune response	-0.14	0.52	-10000	0	-1.2	68	68
IL23/IL23R/JAK2/TYK2	-0.15	0.56	-10000	0	-1.3	68	68
IL6	-0.17	0.56	-10000	0	-1.2	93	93
STAT5A	0.027	0.037	-10000	0	-0.42	3	3
IL2	0.029	0.039	-10000	0	-0.42	3	3
positive regulation of tyrosine phosphorylation of STAT protein	0	0.012	0.081	7	-10000	0	7
CD3E	-0.11	0.45	-10000	0	-1.1	63	63
keratinocyte proliferation	-0.14	0.52	-10000	0	-1.2	68	68
NOS2	-0.11	0.45	-10000	0	-1	70	70

×

Noncanonical Wnt signaling pathway

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
NFATC2	0.03	0.036	-10000	0	-0.42	3	3
GNB1/GNG2	-0.048	0.17	-10000	0	-0.38	63	63
mol:DAG	-0.056	0.15	-10000	0	-0.35	61	61
PLCG1	-0.059	0.15	0.2	3	-0.36	62	65
YES1	-0.066	0.15	-10000	0	-0.41	54	54
FZD3	0.007	0.095	-10000	0	-0.42	23	23
FZD6	-0.028	0.14	-10000	0	-0.42	60	60
G protein	-0.035	0.17	0.29	10	-0.36	58	68
MAP3K7	-0.057	0.12	0.24	2	-0.32	54	56
mol:Ca2+	-0.054	0.14	-10000	0	-0.34	61	61
mol:IP3	-0.056	0.15	-10000	0	-0.35	61	61
NLK	-0.036	0.25	-10000	0	-0.82	45	45
GNB1	0.032	0.045	-10000	0	-0.42	5	5
CAMK2A	-0.056	0.14	0.25	2	-0.32	60	62
MAP3K7IP1	0.034	0.009	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.067	0.15	-10000	0	-0.29	136	136
CSNK1A1	0.036	0.006	-10000	0	-10000	0	0
GNAS	-0.064	0.14	-10000	0	-0.39	52	52
GO:0007205	-0.059	0.14	0.26	2	-0.35	59	61
WNT6	0.03	0.031	-10000	0	-0.42	2	2
WNT4	-0.019	0.14	-10000	0	-0.42	58	58
NFAT1/CK1 alpha	-0.047	0.16	0.29	2	-0.38	52	54
GNG2	0.034	0.021	-10000	0	-0.42	1	1
WNT5A	-0.025	0.15	-10000	0	-0.42	63	63
WNT11	0.027	0.032	-10000	0	-0.42	2	2
CDC42	-0.062	0.15	0.19	2	-0.39	53	55

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	0.004	0.17	0.24	39	-0.34	68	107
FYN	-0.038	0.2	0.29	4	-0.44	71	75
LAT/GRAP2/SLP76	-0.021	0.17	0.24	6	-0.37	71	77
IKBKB	0.03	0.014	-10000	0	-10000	0	0
AKT1	-0.026	0.15	0.25	14	-0.31	80	94
B2M	0.026	0.062	-10000	0	-0.43	9	9
IKBKG	0	0.055	0.13	19	-0.13	26	45
MAP3K8	0.004	0.11	-10000	0	-0.42	32	32
mol:Ca2+	-0.017	0.021	0.093	2	-0.058	66	68
integrin-mediated signaling pathway	0.03	0.048	-10000	0	-0.25	12	12
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.052	0.2	0.26	2	-0.43	84	86
TRPV6	-0.028	0.22	1.2	9	-0.62	1	10
CD28	0	0.12	-10000	0	-0.42	37	37
SHC1	-0.022	0.2	0.24	45	-0.39	83	128
receptor internalization	-0.069	0.2	0.17	1	-0.4	124	125
PRF1	-0.054	0.22	-10000	0	-0.88	22	22
KRAS	0.028	0.054	-10000	0	-0.42	7	7
GRB2	0.033	0.011	-10000	0	-10000	0	0
COT/AKT1	-0.015	0.14	0.25	11	-0.29	67	78
LAT	-0.042	0.19	0.24	13	-0.39	91	104
EntrezGene:6955	0	0.002	-10000	0	-0.016	7	7
CD3D	0.016	0.077	-10000	0	-0.43	14	14
CD3E	0.032	0.015	-10000	0	-10000	0	0
CD3G	-0.021	0.14	-10000	0	-0.42	54	54
RASGRP2	-0.001	0.043	-10000	0	-0.17	27	27
RASGRP1	-0.043	0.17	0.32	2	-0.36	77	79
HLA-A	0.018	0.086	-10000	0	-0.43	18	18
RASSF5	0.019	0.064	-10000	0	-0.42	10	10
RAP1A/GTP/RAPL	0.03	0.048	-10000	0	-0.25	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.016	0.067	0.14	32	-0.12	31	63
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.022	0.071	-10000	0	-0.18	53	53
PRKCA	-0.01	0.09	0.18	9	-0.22	46	55
GRAP2	0.032	0.023	-10000	0	-0.42	1	1
mol:IP3	-0.022	0.14	0.21	30	-0.31	63	93
EntrezGene:6957	0	0.003	0.011	2	-0.021	7	9
TCR/CD3/MHC I/CD8	-0.031	0.14	-10000	0	-0.36	65	65
ORAI1	0.007	0.16	0.59	1	-1	9	10
CSK	-0.045	0.18	0.26	2	-0.41	79	81
B7 family/CD28	-0.027	0.22	0.29	1	-0.47	75	76
CHUK	0.026	0.067	-10000	0	-0.42	11	11
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.06	0.21	0.26	1	-0.42	103	104
PTPN6	-0.053	0.19	0.24	4	-0.42	81	85
VAV1	-0.059	0.2	0.26	2	-0.41	98	100
Monovalent TCR/CD3	-0.018	0.11	-10000	0	-0.3	61	61
CBL	0.032	0.012	-10000	0	-10000	0	0
LCK	-0.046	0.21	0.32	2	-0.48	71	73
PAG1	-0.031	0.19	0.24	11	-0.42	72	83
RAP1A	0.031	0.045	-10000	0	-0.42	5	5
TCR/CD3/MHC I/CD8/LCK	-0.062	0.21	0.28	1	-0.42	104	105
CD80	0.034	0.022	-10000	0	-0.42	1	1
CD86	0.017	0.09	-10000	0	-0.42	20	20
PDK1/CARD11/BCL10/MALT1	-0.013	0.09	-10000	0	-0.22	53	53
HRAS	0.032	0.036	-10000	0	-0.42	3	3
GO:0035030	-0.052	0.17	0.25	1	-0.4	76	77
CD8A	0	0.003	0.011	2	-0.018	7	9
CD8B	0	0.004	0.011	3	-0.017	12	15
PTPRC	0.006	0.095	-10000	0	-0.42	23	23
PDK1/PKC theta	-0.028	0.18	0.32	17	-0.38	76	93
CSK/PAG1	-0.025	0.18	0.23	11	-0.42	64	75
SOS1	0.035	0.021	-10000	0	-0.42	1	1
peptide-MHC class I	0.033	0.088	-10000	0	-0.36	23	23
GRAP2/SLP76	-0.034	0.2	0.29	1	-0.4	86	87
STIM1	0.008	0.11	1.3	3	-10000	0	3
RAS family/GTP	0.013	0.085	0.18	5	-0.18	38	43
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.072	0.21	-10000	0	-0.41	123	123
mol:DAG	-0.042	0.11	0.12	1	-0.27	74	75
RAP1A/GDP	0.011	0.034	0.077	15	-0.068	19	34
PLCG1	0.034	0.008	-10000	0	-10000	0	0
CD247	0	0.002	-10000	0	-0.016	7	7
cytotoxic T cell degranulation	-0.051	0.21	-10000	0	-0.82	23	23
RAP1A/GTP	0	0.018	-10000	0	-0.065	31	31
mol:PI-3-4-5-P3	-0.04	0.17	0.25	2	-0.37	83	85
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.021	0.18	0.23	22	-0.39	66	88
NRAS	0.029	0.054	-10000	0	-0.42	7	7
ZAP70	0.034	0.022	-10000	0	-0.42	1	1
GRB2/SOS1	0.048	0.023	-10000	0	-0.3	1	1
LAT/GRAP2/SLP76/VAV1	-0.031	0.17	0.24	3	-0.39	69	72
MALT1	0.031	0.041	-10000	0	-0.42	4	4
TRAF6	0.035	0.021	-10000	0	-0.42	1	1
CD8 heterodimer	0.001	0.006	0.02	3	-0.027	7	10
CARD11	0.028	0.054	-10000	0	-0.42	7	7
PRKCB	-0.033	0.077	0.11	2	-0.19	78	80
PRKCE	-0.012	0.097	0.18	10	-0.23	50	60
PRKCQ	-0.045	0.19	0.29	3	-0.42	80	83
LCP2	0.024	0.067	-10000	0	-0.42	11	11
BCL10	0.035	0.008	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.019	0.13	0.24	14	-0.27	78	92
IKK complex	0.013	0.061	0.17	31	-0.11	15	46
RAS family/GDP	-0.004	0.015	-10000	0	-0.046	25	25
MAP3K14	-0.014	0.1	0.2	13	-0.23	60	73
PDPK1	-0.021	0.14	0.28	18	-0.3	75	93
TCR/CD3/MHC I/CD8/Fyn	-0.061	0.2	-10000	0	-0.43	92	92

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.035	0.021	-10000	0	-0.42	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.099	0.24	0.62	67	-0.53	2	69
IL27/IL27R/JAK1	-0.088	0.34	0.89	2	-1.1	37	39
TBX21	-0.096	0.3	0.64	20	-0.58	96	116
IL12B	0.026	0.052	-10000	0	-0.42	6	6
IL12A	0.003	0.031	-10000	0	-0.3	5	5
IL6ST	-0.05	0.16	-10000	0	-0.4	87	87
IL27RA/JAK1	-0.063	0.33	0.44	2	-1.2	35	37
IL27	-0.036	0.16	-10000	0	-0.42	73	73
TYK2	0.029	0.029	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.013	0.087	0.2	13	-0.24	55	68
T-helper 2 cell differentiation	0.099	0.24	0.62	67	-0.53	2	69
T cell proliferation during immune response	0.099	0.24	0.62	67	-0.53	2	69
MAPKKK cascade	-0.099	0.24	0.53	2	-0.62	67	69
STAT3	0.028	0.031	-10000	0	-0.42	2	2
STAT2	0.036	0.005	-10000	0	-10000	0	0
STAT1	0.022	0.077	-10000	0	-0.42	14	14
IL12RB1	0.036	0.005	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.081	0.29	0.68	19	-0.6	75	94
IL27/IL27R/JAK2/TYK2	-0.1	0.25	0.53	2	-0.63	67	69
positive regulation of T cell mediated cytotoxicity	-0.099	0.24	0.53	2	-0.62	67	69
STAT1 (dimer)	-0.1	0.39	0.57	30	-0.94	60	90
JAK2	0.024	0.038	-10000	0	-0.43	2	2
JAK1	0.035	0.036	-10000	0	-0.39	3	3
STAT2 (dimer)	-0.084	0.24	0.47	2	-0.6	64	66
T cell proliferation	-0.11	0.25	0.48	2	-0.62	72	74
IL12/IL12R/TYK2/JAK2	0.001	0.2	-10000	0	-0.9	18	18
IL17A	-0.013	0.087	0.2	13	-0.24	55	68
mast cell activation	0.099	0.24	0.62	67	-0.53	2	69
IFNG	-0.01	0.05	0.14	5	-0.13	50	55
T cell differentiation	-0.005	0.01	0.026	10	-0.025	76	86
STAT3 (dimer)	-0.075	0.24	0.47	2	-0.59	64	66
STAT5A (dimer)	-0.076	0.24	0.47	2	-0.6	63	65
STAT4 (dimer)	-0.094	0.26	0.47	2	-0.6	71	73
STAT4	0.01	0.1	-10000	0	-0.42	27	27
T cell activation	-0.002	0.032	0.12	32	-10000	0	32
IL27R/JAK2/TYK2	-0.08	0.32	-10000	0	-1.1	36	36
GATA3	-0.2	0.52	0.82	9	-1.3	91	100
IL18	-0.013	0.074	-10000	0	-0.3	32	32
positive regulation of mast cell cytokine production	-0.073	0.23	0.46	2	-0.57	64	66
IL27/EBI3	-0.008	0.13	0.23	5	-0.31	76	81
IL27RA	-0.091	0.33	-10000	0	-1.3	35	35
IL6	-0.018	0.14	-10000	0	-0.42	52	52
STAT5A	0.027	0.037	-10000	0	-0.42	3	3
monocyte differentiation	0	0.002	-10000	0	-0.013	1	1
IL2	0.022	0.15	0.47	35	-1.2	3	38
IL1B	-0.017	0.082	-10000	0	-0.3	40	40
EBI3	0.026	0.053	-10000	0	-0.43	5	5
TNF	0.002	0.041	-10000	0	-0.3	9	9

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.007	0.004	-10000	0	-10000	0	0
GNB1/GNG2	0.006	0.12	-10000	0	-0.24	102	102
regulation of S phase of mitotic cell cycle	-0.026	0.11	-10000	0	-0.23	100	100
GNAO1	0.03	0.014	-10000	0	-10000	0	0
HRAS	0.032	0.036	-10000	0	-0.42	3	3
SHBG/T-DHT	0.022	0.008	-10000	0	-10000	0	0
PELP1	0.032	0.011	-10000	0	-10000	0	0
AKT1	0.007	0.019	-10000	0	-0.3	2	2
MAP2K1	-0.056	0.097	0.22	4	-0.32	21	25
T-DHT/AR	-0.037	0.13	-10000	0	-0.3	99	99
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-0.006	73	73
GNAI2	0.028	0.054	-10000	0	-0.42	7	7
GNAI3	0.035	0.006	-10000	0	-10000	0	0
GNAI1	0.017	0.087	-10000	0	-0.42	19	19
mol:GDP	-0.073	0.15	-10000	0	-0.37	99	99
cell proliferation	-0.075	0.17	0.29	2	-0.43	76	78
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
FOS	-0.12	0.28	-10000	0	-0.78	75	75
mol:Ca2+	-0.009	0.024	-10000	0	-0.062	58	58
MAPK3	-0.06	0.14	0.28	3	-0.34	68	71
MAPK1	-0.045	0.13	0.21	1	-0.34	50	51
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
mol:IP3	0	0.002	-10000	0	-0.004	73	73
cAMP biosynthetic process	0.003	0.017	-10000	0	-10000	0	0
GNG2	0.034	0.021	-10000	0	-0.42	1	1
potassium channel inhibitor activity	0	0.002	-10000	0	-0.004	73	73
HRAS/GTP	-0.006	0.12	-10000	0	-0.22	99	99
actin cytoskeleton reorganization	0.039	0.051	-10000	0	-0.21	17	17
SRC	0.033	0.03	-10000	0	-0.42	2	2
voltage-gated calcium channel activity	0	0.002	-10000	0	-0.004	73	73
PI3K	0.033	0.056	-10000	0	-0.25	17	17
apoptosis	0.063	0.17	0.43	77	-10000	0	77
T-DHT/AR/PELP1	-0.015	0.12	-10000	0	-0.25	99	99
HRAS/GDP	-0.052	0.16	-10000	0	-0.36	101	101
CREB1	-0.069	0.18	-10000	0	-0.46	77	77
RAC1-CDC42/GTP	0.05	0.056	-10000	0	-0.21	17	17
AR	-0.054	0.18	-10000	0	-0.42	99	99
GNB1	0.032	0.045	-10000	0	-0.42	5	5
RAF1	-0.035	0.1	0.35	1	-0.22	94	95
RAC1-CDC42/GDP	-0.03	0.16	-10000	0	-0.35	98	98
T-DHT/AR/PELP1/Src	0.001	0.12	-10000	0	-0.23	98	98
MAP2K2	-0.057	0.098	0.21	5	-0.32	23	28
T-DHT/AR/PELP1/Src/PI3K	-0.027	0.11	-10000	0	-0.24	100	100
GNAZ	0.023	0.07	-10000	0	-0.42	12	12
SHBG	0.032	0.012	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.037	0.13	-10000	0	-0.4	37	37
mol:T-DHT	0	0.001	0.002	2	-0.002	44	46
RAC1	0.035	0.006	-10000	0	-10000	0	0
GNRH1	0.006	0.014	-10000	0	-0.3	1	1
Gi family/GTP	-0.028	0.084	-10000	0	-0.23	47	47
CDC42	0.035	0.008	-10000	0	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.075	0.28	-10000	0	-0.74	49	49
CRP	-0.044	0.3	0.57	3	-0.77	41	44
cell cycle arrest	-0.095	0.34	0.49	1	-0.8	65	66
TIMP1	-0.069	0.3	-10000	0	-0.79	51	51
IL6ST	-0.049	0.17	-10000	0	-0.42	88	88
Rac1/GDP	-0.05	0.19	0.28	1	-0.42	65	66
AP1	0.013	0.18	-10000	0	-0.51	25	25
GAB2	0.033	0.014	-10000	0	-10000	0	0
TNFSF11	-0.14	0.4	-10000	0	-0.98	79	79
HSP90B1	0	0.12	-10000	0	-0.83	8	8
GAB1	0.028	0.061	-10000	0	-0.42	9	9
MAPK14	-0.045	0.17	-10000	0	-0.52	33	33
AKT1	0.03	0.081	-10000	0	-0.42	5	5
FOXO1	0.037	0.08	-10000	0	-0.4	5	5
MAP2K6	-0.05	0.16	0.24	1	-0.42	55	56
mol:GTP	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.061	0.21	0.33	2	-0.46	69	71
MITF	-0.054	0.17	0.24	1	-0.4	65	66
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.036	0.005	-10000	0	-10000	0	0
A2M	-0.053	0.33	-10000	0	-1.3	32	32
CEBPB	0.027	0.05	-10000	0	-0.42	6	6
GRB2/SOS1/GAB family/SHP2	0.005	0.12	0.3	1	-0.43	17	18
STAT3	-0.11	0.37	0.5	1	-0.89	64	65
STAT1	-0.01	0.17	-10000	0	-0.88	17	17
CEBPD	-0.097	0.37	0.59	1	-0.91	67	68
PIK3CA	0.034	0.022	-10000	0	-0.42	1	1
PI3K	0.038	0.066	-10000	0	-0.3	17	17
JUN	-0.001	0.12	-10000	0	-0.42	39	39
PIAS3/MITF	-0.045	0.17	-10000	0	-0.4	59	59
MAPK11	-0.044	0.16	-10000	0	-0.52	32	32
STAT3 (dimer)/FOXO1	-0.052	0.28	0.46	2	-0.66	51	53
GRB2/SOS1/GAB family	-0.017	0.17	0.3	1	-0.43	37	38
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.062	0.17	-10000	0	-0.38	78	78
GRB2	0.034	0.011	-10000	0	-10000	0	0
JAK2	0.032	0.03	-10000	0	-0.42	2	2
LBP	-0.031	0.23	0.45	1	-0.62	36	37
PIK3R1	0.02	0.08	-10000	0	-0.42	16	16
JAK1	0.031	0.039	-10000	0	-0.42	3	3
MYC	-0.067	0.37	0.59	2	-0.91	59	61
FGG	-0.076	0.29	-10000	0	-0.75	48	48
macrophage differentiation	-0.095	0.34	0.49	1	-0.8	65	66
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.023	0.16	-10000	0	-0.25	132	132
JUNB	-0.075	0.28	-10000	0	-0.76	42	42
FOS	-0.031	0.15	-10000	0	-0.42	66	66
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.06	0.17	0.27	1	-0.4	71	72
STAT1/PIAS1	-0.046	0.19	0.3	2	-0.42	66	68
GRB2/SOS1/GAB family/SHP2/PI3K	0.031	0.081	-10000	0	-0.36	10	10
STAT3 (dimer)	-0.1	0.36	0.49	1	-0.87	65	66
PRKCD	-0.072	0.24	0.36	1	-0.56	68	69
IL6R	0.021	0.06	-10000	0	-0.43	8	8
SOCS3	-0.042	0.19	0.43	1	-0.73	19	20
gp130 (dimer)/JAK1/JAK1/LMO4	-0.027	0.15	-10000	0	-0.26	135	135
Rac1/GTP	-0.053	0.2	0.28	1	-0.43	69	70
HCK	0.018	0.087	-10000	0	-0.42	19	19
MAPKKK cascade	0.021	0.14	-10000	0	-0.55	18	18
bone resorption	-0.13	0.37	-10000	0	-0.89	80	80
IRF1	-0.09	0.32	-10000	0	-0.83	53	53
mol:GDP	-0.056	0.18	0.24	1	-0.41	69	70
SOS1	0.036	0.022	-10000	0	-0.42	1	1
VAV1	-0.057	0.18	0.24	1	-0.41	70	71
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.043	0.18	-10000	0	-0.52	40	40
PTPN11	0.016	0.091	-10000	0	-1.1	3	3
IL6/IL6RA	0.004	0.1	-10000	0	-0.3	47	47
gp130 (dimer)/TYK2/TYK2/LMO4	-0.022	0.14	-10000	0	-0.25	133	133
gp130 (dimer)/JAK2/JAK2/LMO4	-0.024	0.15	-10000	0	-0.26	134	134
IL6	-0.021	0.14	-10000	0	-0.42	52	52
PIAS3	0.035	0.006	-10000	0	-10000	0	0
PTPRE	0.02	0.07	-10000	0	-0.41	12	12
PIAS1	0.035	0.007	-10000	0	-10000	0	0
RAC1	0.036	0.006	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.053	0.13	0.23	1	-0.31	69	70
LMO4	-0.019	0.14	-10000	0	-0.42	53	53
STAT3 (dimer)/PIAS3	-0.09	0.34	-10000	0	-0.82	61	61
MCL1	0.038	0.094	-10000	0	-0.78	2	2

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.031	0.072	-10000	0	-0.21	34	34
NF kappa B1 p50/RelA/I kappa B alpha	0.021	0.095	0.27	6	-0.27	13	19
AP1	-0.034	0.12	-10000	0	-0.25	100	100
mol:PIP3	-0.031	0.091	-10000	0	-0.22	88	88
AKT1	-0.005	0.1	0.25	3	-0.31	26	29
PTK2B	-0.042	0.1	0.14	1	-0.22	112	113
RHOA	-0.015	0.1	-10000	0	-0.32	35	35
PIK3CB	0.031	0.045	-10000	0	-0.42	5	5
mol:Ca2+	-0.01	0.091	0.19	41	-0.2	53	94
MAGI3	0.013	0.099	-10000	0	-0.42	25	25
RELA	0.035	0.006	-10000	0	-10000	0	0
apoptosis	0.003	0.054	-10000	0	-0.18	39	39
HRAS/GDP	0.024	0.025	-10000	0	-0.3	3	3
positive regulation of microtubule depolymerization	-0.075	0.12	0.18	3	-0.24	129	132
NF kappa B1 p50/RelA	-0.02	0.082	-10000	0	-0.21	63	63
endothelial cell migration	-0.01	0.12	-10000	0	-0.51	27	27
ADCY4	-0.016	0.089	-10000	0	-0.27	44	44
ADCY5	-0.016	0.086	-10000	0	-0.25	47	47
ADCY6	-0.014	0.083	-10000	0	-0.25	46	46
ADCY7	-0.015	0.089	-10000	0	-0.27	42	42
ADCY1	-0.014	0.084	-10000	0	-0.26	44	44
ADCY2	-0.026	0.1	-10000	0	-0.26	67	67
ADCY3	-0.015	0.085	-10000	0	-0.25	46	46
ADCY8	-0.013	0.075	-10000	0	-0.25	37	37
ADCY9	-0.016	0.081	-10000	0	-0.23	50	50
GSK3B	-0.042	0.098	0.16	1	-0.21	107	108
arachidonic acid secretion	-0.018	0.09	-10000	0	-0.26	49	49
GNG2	0.034	0.021	-10000	0	-0.42	1	1
TRIP6	0.009	0.071	-10000	0	-0.36	17	17
GNAO1	0.006	0.055	-10000	0	-0.22	27	27
HRAS	0.032	0.036	-10000	0	-0.42	3	3
NFKBIA	-0.008	0.091	0.24	8	-0.26	19	27
GAB1	0.027	0.061	-10000	0	-0.42	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.022	0.2	-10000	0	-0.92	22	22
JUN	-0.001	0.12	-10000	0	-0.42	39	39
LPA/LPA2/NHERF2	-0.004	0.077	-10000	0	-0.19	64	64
TIAM1	0	0.23	-10000	0	-1.1	22	22
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
mol:IP3	-0.009	0.09	0.19	41	-0.21	50	91
PLCB3	0.01	0.09	0.19	46	-0.23	42	88
FOS	-0.031	0.15	-10000	0	-0.42	66	66
positive regulation of mitosis	-0.018	0.09	-10000	0	-0.26	49	49
LPA/LPA1-2-3	-0.007	0.05	-10000	0	-0.17	42	42
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.03	0.014	-10000	0	-10000	0	0
stress fiber formation	-0.006	0.082	-10000	0	-0.27	23	23
GNAZ	-0.001	0.072	-10000	0	-0.21	49	49
EGFR/PI3K-beta/Gab1	-0.023	0.098	-10000	0	-0.22	89	89
positive regulation of dendritic cell cytokine production	-0.007	0.05	-10000	0	-0.17	42	42
LPA/LPA2/MAGI-3	0.005	0.065	-10000	0	-0.17	49	49
ARHGEF1	0.027	0.077	0.19	54	-0.21	22	76
GNAI2	0.001	0.069	-10000	0	-0.21	45	45
GNAI3	0.006	0.058	-10000	0	-0.19	38	38
GNAI1	-0.005	0.082	-10000	0	-0.23	54	54
LPA/LPA3	-0.005	0.025	-10000	0	-0.086	42	42
LPA/LPA2	-0.004	0.025	-10000	0	-0.085	42	42
LPA/LPA1	-0.01	0.067	-10000	0	-0.22	42	42
HB-EGF/EGFR	-0.026	0.13	-10000	0	-0.28	91	91
HBEGF	-0.02	0.099	-10000	0	-0.3	56	56
mol:DAG	-0.009	0.09	0.19	41	-0.21	50	91
cAMP biosynthetic process	-0.02	0.09	0.2	3	-0.26	46	49
NFKB1	0.036	0.005	-10000	0	-10000	0	0
SRC	0.033	0.029	-10000	0	-0.42	2	2
GNB1	0.032	0.045	-10000	0	-0.42	5	5
LYN	0.005	0.094	0.24	20	-0.24	17	37
GNAQ	-0.004	0.02	-10000	0	-0.07	42	42
LPAR2	0	0.001	-10000	0	-10000	0	0
LPAR3	0	0	-10000	0	-10000	0	0
LPAR1	-0.008	0.039	-10000	0	-0.13	42	42
IL8	-0.072	0.18	-10000	0	-0.42	88	88
PTK2	0.011	0.042	-10000	0	-0.16	26	26
Rac1/GDP	0.026	0.004	-10000	0	-10000	0	0
CASP3	0.003	0.054	-10000	0	-0.18	39	39
EGFR	-0.015	0.13	-10000	0	-0.42	49	49
PLCG1	-0.002	0.042	-10000	0	-0.12	47	47
PLD2	0.01	0.053	-10000	0	-0.17	38	38
G12/G13	0.03	0.063	-10000	0	-0.18	35	35
PI3K-beta	-0.019	0.1	-10000	0	-0.34	28	28
cell migration	0.008	0.068	-10000	0	-0.26	22	22
SLC9A3R2	-0.004	0.12	-10000	0	-0.42	40	40
PXN	-0.007	0.083	-10000	0	-0.28	23	23
HRAS/GTP	-0.019	0.092	-10000	0	-0.27	49	49
RAC1	0.035	0.006	-10000	0	-10000	0	0
MMP9	-0.013	0.14	-10000	0	-0.42	52	52
PRKCE	0.03	0.05	-10000	0	-0.42	6	6
PRKCD	-0.011	0.088	0.18	41	-0.21	41	82
Gi(beta/gamma)	-0.009	0.088	-10000	0	-0.25	45	45
mol:LPA	-0.008	0.039	-10000	0	-0.13	42	42
TRIP6/p130 Cas/FAK1/Paxillin	0.009	0.081	-10000	0	-0.29	17	17
MAPKKK cascade	-0.018	0.09	-10000	0	-0.26	49	49
contractile ring contraction involved in cytokinesis	-0.016	0.1	-10000	0	-0.32	37	37
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.014	0.074	-10000	0	-0.2	57	57
GNA15	0.007	0.035	-10000	0	-0.11	28	28
GNA12	0.035	0.007	-10000	0	-10000	0	0
GNA13	0.029	0.037	-10000	0	-0.42	3	3
MAPT	-0.077	0.12	0.18	3	-0.25	129	132
GNA11	0.008	0.03	-10000	0	-0.097	28	28
Rac1/GTP	0.021	0.22	-10000	0	-0.98	22	22
MMP2	-0.01	0.12	-10000	0	-0.52	27	27

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.016	0.036	-10000	0	-0.26	11	11
SNTA1	0.032	0.041	-10000	0	-0.42	4	4
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.022	0.05	-10000	0	-0.26	22	22
MAPK12	0.004	0.085	0.21	41	-0.23	34	75
CCND1	-0.056	0.16	-10000	0	-0.42	81	81
p38 gamma/SNTA1	0.026	0.09	0.21	51	-0.22	39	90
MAP2K3	0.032	0.023	-10000	0	-0.42	1	1
PKN1	0.033	0.035	-10000	0	-0.42	3	3
G2/M transition checkpoint	0.004	0.084	0.21	41	-0.23	34	75
MAP2K6	0.013	0.096	0.24	46	-0.24	34	80
MAPT	-0.054	0.13	0.27	6	-0.28	105	111
MAPK13	0.006	0.052	-10000	0	-0.3	14	14
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.005	0.064	-10000	0	-0.29	23	23

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.027	0.18	-10000	0	-0.46	62	62
Syndecan-4/Syndesmos	-0.033	0.2	-10000	0	-0.49	61	61
positive regulation of JNK cascade	-0.045	0.22	-10000	0	-0.48	76	76
Syndecan-4/ADAM12	-0.051	0.23	-10000	0	-0.51	81	81
CCL5	-0.014	0.14	-10000	0	-0.42	52	52
Rac1/GDP	0.026	0.004	-10000	0	-10000	0	0
DNM2	0.036	0.005	-10000	0	-10000	0	0
ITGA5	0.034	0.029	-10000	0	-0.42	2	2
SDCBP	0.023	0.058	-10000	0	-0.42	8	8
PLG	0.022	0.04	-10000	0	-0.31	3	3
ADAM12	-0.014	0.14	-10000	0	-0.42	53	53
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.028	0.046	-10000	0	-0.42	5	5
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.032	0.019	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.033	0.21	-10000	0	-0.5	66	66
Syndecan-4/CXCL12/CXCR4	-0.048	0.23	-10000	0	-0.52	76	76
Syndecan-4/Laminin alpha3	-0.055	0.22	-10000	0	-0.51	68	68
MDK	0.018	0.085	-10000	0	-0.42	18	18
Syndecan-4/FZD7	-0.049	0.22	-10000	0	-0.5	75	75
Syndecan-4/Midkine	-0.039	0.21	-10000	0	-0.5	67	67
FZD7	-0.006	0.13	-10000	0	-0.42	43	43
Syndecan-4/FGFR1/FGF	-0.033	0.2	-10000	0	-0.47	64	64
THBS1	0.001	0.12	-10000	0	-0.42	37	37
integrin-mediated signaling pathway	-0.04	0.21	-10000	0	-0.48	75	75
positive regulation of MAPKKK cascade	-0.045	0.22	-10000	0	-0.48	76	76
Syndecan-4/TACI	-0.034	0.21	-10000	0	-0.5	66	66
CXCR4	0.007	0.11	-10000	0	-0.42	30	30
cell adhesion	0.012	0.1	0.2	46	-0.27	41	87
Syndecan-4/Dynamin	-0.031	0.21	-10000	0	-0.5	66	66
Syndecan-4/TSP1	-0.045	0.22	-10000	0	-0.5	73	73
Syndecan-4/GIPC	-0.031	0.21	-10000	0	-0.49	66	66
Syndecan-4/RANTES	-0.053	0.22	-10000	0	-0.51	70	70
ITGB1	0.032	0.036	-10000	0	-0.42	3	3
LAMA1	0.034	0.009	-10000	0	-10000	0	0
LAMA3	-0.019	0.14	-10000	0	-0.42	58	58
RAC1	0.035	0.006	-10000	0	-10000	0	0
PRKCA	0.087	0.26	0.8	57	-10000	0	57
Syndecan-4/alpha-Actinin	-0.034	0.22	-10000	0	-0.51	67	67
TFPI	0.034	0.008	-10000	0	-10000	0	0
F2	0.031	0.024	-10000	0	-10000	0	0
alpha5/beta1 Integrin	0.048	0.037	-10000	0	-0.3	5	5
positive regulation of cell adhesion	-0.061	0.2	-10000	0	-0.5	68	68
ACTN1	0.027	0.061	-10000	0	-0.42	9	9
TNC	0.004	0.11	-10000	0	-0.42	31	31
Syndecan-4/CXCL12	-0.049	0.22	-10000	0	-0.51	74	74
FGF6	0.027	0.057	-10000	0	-0.42	8	8
RHOA	0.026	0.061	-10000	0	-0.42	9	9
CXCL12	-0.008	0.13	-10000	0	-0.42	47	47
TNFRSF13B	0.032	0.012	-10000	0	-10000	0	0
FGF2	-0.001	0.11	-10000	0	-0.42	34	34
FGFR1	0.02	0.064	-10000	0	-0.42	10	10
Syndecan-4/PI-4-5-P2	-0.058	0.19	-10000	0	-0.49	66	66
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.019	0.13	-10000	0	-0.4	51	51
cell migration	-0.015	0.015	-10000	0	-10000	0	0
PRKCD	0.024	0.039	-10000	0	-0.3	3	3
vasculogenesis	-0.043	0.21	-10000	0	-0.48	73	73
SDC4	-0.057	0.21	-10000	0	-0.52	66	66
Syndecan-4/Tenascin C	-0.043	0.22	-10000	0	-0.5	75	75
Syndecan-4/PI-4-5-P2/PKC alpha	-0.026	0.016	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.034	0.2	-10000	0	-0.5	61	61
MMP9	-0.013	0.14	-10000	0	-0.42	52	52
Rac1/GTP	0.012	0.1	0.2	46	-0.28	41	87
cytoskeleton organization	-0.031	0.19	-10000	0	-0.48	61	61
GIPC1	0.033	0.035	-10000	0	-0.42	3	3
Syndecan-4/TFPI	-0.034	0.21	-10000	0	-0.5	66	66

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	-0.012	0.089	0.22	2	-0.27	23	25
adherens junction organization	-0.045	0.13	-10000	0	-0.28	86	86
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.013	0.11	0.27	4	-0.26	33	37
FMN1	-0.036	0.12	-10000	0	-0.26	86	86
mol:IP3	-0.016	0.076	-10000	0	-0.23	25	25
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.035	0.13	-10000	0	-0.27	86	86
CTNNB1	0.026	0.067	-10000	0	-0.42	11	11
AKT1	-0.017	0.093	0.19	1	-0.28	21	22
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.062	0.19	-10000	0	-0.43	73	73
CTNND1	0.035	0.022	-10000	0	-0.42	1	1
mol:PI-4-5-P2	-0.032	0.12	0.22	1	-0.26	79	80
VASP	-0.039	0.12	-10000	0	-0.27	83	83
ZYX	-0.038	0.12	-10000	0	-0.26	86	86
JUB	-0.047	0.13	-10000	0	-0.28	87	87
EGFR(dimer)	-0.041	0.14	0.23	1	-0.27	102	103
E-cadherin/beta catenin-gamma catenin	0.015	0.099	-10000	0	-0.24	58	58
mol:PI-3-4-5-P3	-0.001	0.11	0.23	2	-0.26	28	30
PIK3CA	0.034	0.022	-10000	0	-0.42	1	1
PI3K	-0.001	0.11	0.23	2	-0.26	28	30
FYN	-0.017	0.092	0.22	2	-0.28	26	28
mol:Ca2+	-0.015	0.074	-10000	0	-0.22	25	25
JUP	0.03	0.042	-10000	0	-0.42	4	4
PIK3R1	0.02	0.08	-10000	0	-0.42	16	16
mol:DAG	-0.016	0.076	-10000	0	-0.23	25	25
CDH1	-0.011	0.13	-10000	0	-0.42	45	45
RhoA/GDP	-0.016	0.11	0.26	3	-0.27	33	36
establishment of polarity of embryonic epithelium	-0.037	0.12	0.22	1	-0.26	83	84
SRC	0.033	0.029	-10000	0	-0.42	2	2
RAC1	0.035	0.006	-10000	0	-10000	0	0
RHOA	0.026	0.061	-10000	0	-0.42	9	9
EGFR	-0.015	0.13	-10000	0	-0.42	49	49
CASR	-0.013	0.078	0.22	2	-0.23	22	24
RhoA/GTP	-0.001	0.09	0.21	2	-0.25	18	20
AKT2	-0.016	0.093	0.19	2	-0.28	19	21
actin cable formation	-0.037	0.12	0.2	6	-0.26	83	89
apoptosis	0.009	0.099	0.27	26	-0.24	5	31
CTNNA1	0.036	0.022	-10000	0	-0.43	1	1
mol:GDP	-0.03	0.1	0.22	2	-0.27	34	36
PIP5K1A	-0.034	0.12	-10000	0	-0.26	79	79
PLCG1	-0.016	0.077	-10000	0	-0.23	25	25
Rac1/GTP	-0.03	0.14	-10000	0	-0.3	55	55
homophilic cell adhesion	0	0.003	-10000	0	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.017	0.08	-10000	0	-0.42	16	16
EPHB2	0.033	0.03	-10000	0	-0.42	2	2
EFNB1	0.015	0.029	-10000	0	-0.3	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.073	0.065	-10000	0	-0.23	17	17
Ephrin B2/EPHB1-2	0.044	0.067	-10000	0	-0.24	23	23
neuron projection morphogenesis	0.048	0.056	-10000	0	-0.22	17	17
Ephrin B1/EPHB1-2/Tiam1	0.064	0.064	-10000	0	-0.24	17	17
DNM1	0.034	0.035	-10000	0	-0.42	3	3
cell-cell signaling	0	0.003	-10000	0	-10000	0	0
MAP2K4	-0.082	0.21	-10000	0	-0.55	79	79
YES1	-0.11	0.3	-10000	0	-0.8	79	79
Ephrin B1/EPHB1-2/NCK2	0.069	0.051	-10000	0	-0.22	12	12
PI3K	-0.049	0.23	-10000	0	-0.56	79	79
mol:GDP	0.062	0.063	-10000	0	-0.24	17	17
ITGA2B	0.034	0.01	-10000	0	-10000	0	0
endothelial cell proliferation	0.02	0.081	-10000	0	-0.26	35	35
FYN	-0.11	0.3	-10000	0	-0.8	79	79
MAP3K7	-0.082	0.22	-10000	0	-0.59	76	76
FGR	-0.1	0.3	-10000	0	-0.78	79	79
TIAM1	0.028	0.057	-10000	0	-0.42	8	8
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
RGS3	0.036	0.005	-10000	0	-10000	0	0
cell adhesion	-0.057	0.21	-10000	0	-0.52	79	79
LYN	-0.1	0.3	-10000	0	-0.79	79	79
Ephrin B1/EPHB1-2/Src Family Kinases	-0.1	0.28	-10000	0	-0.74	79	79
Ephrin B1/EPHB1-2	-0.089	0.24	-10000	0	-0.64	78	78
SRC	-0.1	0.3	-10000	0	-0.79	79	79
ITGB3	0.029	0.046	-10000	0	-0.42	5	5
EPHB1	0.027	0.05	-10000	0	-0.42	6	6
EPHB4	0.016	0.091	-10000	0	-0.42	21	21
RAC1	0.035	0.006	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.021	0.081	-10000	0	-0.26	35	35
alphaIIb/beta3 Integrin	0.046	0.035	-10000	0	-0.3	4	4
BLK	-0.12	0.3	-10000	0	-0.8	79	79
HCK	-0.11	0.3	-10000	0	-0.79	79	79
regulation of stress fiber formation	-0.067	0.05	0.22	12	-10000	0	12
MAPK8	-0.08	0.2	-10000	0	-0.53	79	79
Ephrin B1/EPHB1-2/RGS3	0.069	0.051	-10000	0	-0.22	12	12
endothelial cell migration	-0.079	0.19	-10000	0	-0.51	75	75
NCK2	0.036	0.005	-10000	0	-10000	0	0
PTPN13	-0.046	0.2	-10000	0	-0.54	72	72
regulation of focal adhesion formation	-0.067	0.05	0.22	12	-10000	0	12
chemotaxis	-0.066	0.05	0.22	12	-10000	0	12
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
Rac1/GTP	0.062	0.061	-10000	0	-0.23	17	17
angiogenesis	-0.09	0.23	-10000	0	-0.63	79	79
LCK	-0.12	0.3	-10000	0	-0.8	79	79

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.015	0.032	-10000	0	-0.25	6	6
ARNO/beta Arrestin1-2	0.014	0.069	-10000	0	-0.19	42	42
EGFR	-0.015	0.13	-10000	0	-0.42	49	49
EPHA2	0.032	0.036	-10000	0	-0.42	3	3
USP6	0.032	0.012	-10000	0	-10000	0	0
IQSEC1	0.034	0.021	-10000	0	-0.42	1	1
EGFR/EGFR/EGF/EGF	-0.061	0.16	-10000	0	-0.3	152	152
ARRB2	0.011	0.043	-10000	0	-0.3	9	9
mol:GTP	0.006	0.02	0.11	5	-0.11	2	7
ARRB1	0.027	0.05	-10000	0	-0.42	6	6
FBXO8	0.035	0.007	-10000	0	-10000	0	0
TSHR	0.029	0.05	-10000	0	-0.42	6	6
EGF	-0.069	0.19	-10000	0	-0.42	110	110
somatostatin receptor activity	0	0	0	2	-0.001	70	72
ARAP2	0	0	0	2	0	69	71
mol:GDP	-0.029	0.1	-10000	0	-0.26	56	56
mol:PI-3-4-5-P3	0	0	0	3	-0.001	69	72
ITGA2B	0.034	0.01	-10000	0	-10000	0	0
ARF6	0.033	0.029	-10000	0	-0.42	2	2
Ephrin A1/EPHA2/NCK1/GIT1	0.053	0.072	-10000	0	-0.23	20	20
ADAP1	0	0	0	3	0	40	43
KIF13B	0.022	0.051	-10000	0	-0.42	6	6
HGF/MET	0.042	0.055	-10000	0	-0.3	12	12
PXN	0.036	0.004	-10000	0	-10000	0	0
ARF6/GTP	-0.034	0.1	0.17	2	-0.24	65	67
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.035	0.15	-10000	0	-0.26	151	151
ADRB2	0.003	0.11	-10000	0	-0.42	33	33
receptor agonist activity	0	0	0	3	0	52	55
actin filament binding	0	0	0	2	0	77	79
SRC	0.033	0.029	-10000	0	-0.42	2	2
ITGB3	0.029	0.046	-10000	0	-0.42	5	5
GNAQ	0	0	0.001	4	-0.001	52	56
EFA6/PI-4-5-P2	0	0	0.001	5	-0.001	47	52
ARF6/GDP	0.004	0.075	0.2	2	-0.26	15	17
ARF6/GDP/GULP/ACAP1	-0.017	0.13	-10000	0	-0.28	63	63
alphaIIb/beta3 Integrin/paxillin/GIT1	0.079	0.043	-10000	0	-0.23	5	5
ACAP1	0	0	0	1	-10000	0	1
ACAP2	0	0	0	2	0	71	73
LHCGR/beta Arrestin2	0.018	0.06	-10000	0	-0.38	9	9
EFNA1	0.014	0.08	-10000	0	-0.42	16	16
HGF	0.028	0.057	-10000	0	-0.42	8	8
CYTH3	0	0	0.001	4	-0.001	51	55
CYTH2	-0.001	0.002	-10000	0	-0.004	80	80
NCK1	0.034	0.021	-10000	0	-0.42	1	1
fibronectin binding	0	0	0	3	0	48	51
endosomal lumen acidification	0	0	0	3	0	64	67
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	0	0.12	-10000	0	-0.42	39	39
GNAQ/ARNO	-0.001	0.003	0.007	5	-0.006	43	48
mol:Phosphatidic acid	0	0	0	2	0	71	73
PIP3-E	0.029	0.037	-10000	0	-0.42	3	3
MET	0.03	0.041	-10000	0	-0.42	4	4
GNA14	-0.009	0.13	-10000	0	-0.42	43	43
GNA15	0.03	0.046	-10000	0	-0.42	5	5
GIT1	0.034	0.022	-10000	0	-0.42	1	1
mol:PI-4-5-P2	0	0	0.001	3	-0.001	52	55
GNA11	0.033	0.036	-10000	0	-0.42	3	3
LHCGR	0.027	0.061	-10000	0	-0.42	9	9
AGTR1	-0.047	0.16	-10000	0	-0.42	80	80
desensitization of G-protein coupled receptor protein signaling pathway	0.018	0.06	-10000	0	-0.38	9	9
IPCEF1/ARNO	-0.024	0.12	-10000	0	-0.2	150	150
alphaIIb/beta3 Integrin	0.046	0.035	-10000	0	-0.3	4	4

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.07	0.16	-10000	0	-0.41	66	66
KLHL20	-0.025	0.09	0.25	1	-0.25	17	18
CYFIP2	-0.006	0.13	-10000	0	-0.42	45	45
Rac1/GDP	-0.035	0.12	0.27	4	-0.26	60	64
ENAH	-0.065	0.16	-10000	0	-0.35	110	110
AP1M1	0.035	0.021	-10000	0	-0.42	1	1
RAP1B	0.033	0.03	-10000	0	-0.42	2	2
RAP1A	0.031	0.045	-10000	0	-0.42	5	5
CTNNB1	0.025	0.067	-10000	0	-0.42	11	11
CDC42/GTP	-0.013	0.083	-10000	0	-0.23	13	13
ABI1/Sra1/Nap1	-0.046	0.054	-10000	0	-0.16	40	40
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.03	0.1	-10000	0	-0.23	58	58
RAPGEF1	-0.073	0.15	0.24	2	-0.36	80	82
CTNND1	0.034	0.022	-10000	0	-0.42	1	1
regulation of calcium-dependent cell-cell adhesion	-0.074	0.18	-10000	0	-0.35	144	144
CRK	-0.069	0.16	-10000	0	-0.39	81	81
E-cadherin/gamma catenin/alpha catenin	0.018	0.098	-10000	0	-0.26	49	49
alphaE/beta7 Integrin	0.044	0.039	-10000	0	-0.3	5	5
IQGAP1	0.035	0.008	-10000	0	-10000	0	0
NCKAP1	0.035	0.021	-10000	0	-0.42	1	1
Rap1/GTP/I-afadin	0.047	0.064	-10000	0	-0.23	22	22
DLG1	-0.082	0.18	-10000	0	-0.34	146	146
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.031	0.056	-10000	0	-0.15	60	60
MLLT4	0.02	0.078	-10000	0	-0.42	15	15
ARF6/GTP/NME1/Tiam1	0.056	0.045	-10000	0	-0.24	9	9
PI3K	-0.036	0.074	-10000	0	-0.2	57	57
ARF6	0.033	0.029	-10000	0	-0.42	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.004	0.1	-10000	0	-0.3	48	48
TIAM1	0.028	0.057	-10000	0	-0.42	8	8
E-cadherin(dimer)/Ca2+	0.03	0.097	-10000	0	-0.22	57	57
AKT1	-0.024	0.053	0.17	3	-0.17	5	8
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
CDH1	-0.012	0.13	-10000	0	-0.42	45	45
RhoA/GDP	-0.036	0.12	0.27	4	-0.27	63	67
actin cytoskeleton organization	-0.017	0.068	0.18	2	-0.18	16	18
CDC42/GDP	-0.033	0.12	0.27	4	-0.26	60	64
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.01	0.077	-10000	0	-0.22	56	56
ITGB7	0.036	0.005	-10000	0	-10000	0	0
RAC1	0.035	0.006	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.033	0.1	-10000	0	-0.23	57	57
E-cadherin/Ca2+/beta catenin/alpha catenin	0.018	0.087	-10000	0	-0.22	56	56
mol:GDP	-0.054	0.12	0.27	4	-0.3	64	68
CDC42/GTP/IQGAP1	0.045	0.014	-10000	0	-10000	0	0
JUP	0.028	0.042	-10000	0	-0.42	4	4
p120 catenin/RhoA/GDP	-0.031	0.13	0.28	3	-0.28	63	66
RAC1/GTP/IQGAP1	0.046	0.013	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.049	0.033	-10000	0	-0.3	4	4
RHOA	0.026	0.061	-10000	0	-0.42	9	9
CDC42	0.035	0.008	-10000	0	-10000	0	0
CTNNA1	0.035	0.021	-10000	0	-0.42	1	1
positive regulation of S phase of mitotic cell cycle	-0.03	0.077	0.15	1	-0.18	80	81
NME1	0.033	0.01	-10000	0	-10000	0	0
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.08	0.18	-10000	0	-0.4	83	83
regulation of cell-cell adhesion	-0.018	0.069	-10000	0	-0.17	54	54
WASF2	-0.016	0.042	0.12	2	-0.11	12	14
Rap1/GTP	-0.015	0.091	0.25	1	-0.25	13	14
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.036	0.1	-10000	0	-0.23	53	53
CCND1	-0.038	0.094	0.17	1	-0.23	80	81
VAV2	-0.068	0.18	-10000	0	-0.51	18	18
RAP1/GDP	-0.02	0.1	0.26	1	-0.26	17	18
adherens junction assembly	-0.078	0.17	-10000	0	-0.39	85	85
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.035	0.008	-10000	0	-10000	0	0
PIP5K1C	0.033	0.036	-10000	0	-0.42	3	3
regulation of heterotypic cell-cell adhesion	0.028	0.11	-10000	0	-0.22	62	62
E-cadherin/beta catenin	-0.024	0.1	-10000	0	-0.29	63	63
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.081	0.18	-10000	0	-0.4	87	87
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
Rac1/GTP	-0.076	0.13	-10000	0	-0.38	32	32
E-cadherin/beta catenin/alpha catenin	0.02	0.1	-10000	0	-0.25	56	56
ITGAE	0.028	0.046	-10000	0	-0.42	5	5
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.076	0.19	-10000	0	-0.36	143	143

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.015	0.12	-10000	0	-0.43	23	23
UGCG	-0.09	0.27	-10000	0	-0.73	73	73
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.062	0.19	0.31	1	-0.38	99	100
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.088	0.26	-10000	0	-0.71	74	74
mol:DAG	-0.006	0.029	0.17	12	-10000	0	12
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.079	0.23	0.34	1	-0.44	115	116
FRAP1	-0.1	0.26	0.36	1	-0.5	115	116
FOXO3	-0.049	0.21	0.36	1	-0.5	54	55
AKT1	-0.054	0.22	0.37	1	-0.54	54	55
GAB2	0.029	0.015	-10000	0	-10000	0	0
SMPD1	-0.005	0.13	-10000	0	-0.68	16	16
SGMS1	-0.004	0.035	0.058	2	-0.077	51	53
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	-0.008	0.048	-10000	0	-0.25	17	17
CALM1	0.035	0.007	-10000	0	-10000	0	0
cell proliferation	-0.041	0.19	0.25	5	-0.37	95	100
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	0.034	0.066	-10000	0	-0.3	17	17
RPS6KB1	-0.043	0.16	-10000	0	-0.8	14	14
mol:sphingomyelin	-0.006	0.029	0.17	12	-10000	0	12
natural killer cell activation	-0.002	0.004	-10000	0	-0.015	17	17
JAK3	0.035	0.008	-10000	0	-10000	0	0
PIK3R1	0.018	0.08	-10000	0	-0.42	16	16
JAK1	0.032	0.036	-10000	0	-0.42	3	3
NFKB1	0.036	0.005	-10000	0	-10000	0	0
MYC	-0.027	0.29	0.49	2	-0.95	35	37
MYB	-0.23	0.5	-10000	0	-1.2	104	104
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.021	0.15	-10000	0	-0.37	47	47
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.025	0.16	-10000	0	-0.69	15	15
mol:PI-3-4-5-P3	-0.02	0.15	-10000	0	-0.37	47	47
Rac1/GDP	0.008	0.051	-10000	0	-0.23	17	17
T cell proliferation	-0.018	0.14	0.29	3	-0.34	46	49
SHC1	0.026	0.026	-10000	0	-0.42	1	1
RAC1	0.035	0.006	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.01	0.028	-10000	0	-0.065	103	103
PRKCZ	-0.021	0.15	-10000	0	-0.36	46	46
NF kappa B1 p50/RelA	-0.069	0.24	0.36	1	-0.45	107	108
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.013	0.13	-10000	0	-0.42	32	32
HSP90AA1	0	0	-10000	0	-10000	0	0
RELA	0.035	0.006	-10000	0	-10000	0	0
IL2RA	0.002	0.11	-10000	0	-0.42	31	31
IL2RB	0.011	0.097	-10000	0	-0.42	24	24
TERT	0.032	0.03	-10000	0	-0.42	2	2
E2F1	-0.072	0.2	-10000	0	-0.43	113	113
SOS1	0.032	0.023	-10000	0	-0.43	1	1
RPS6	0.034	0.022	-10000	0	-0.42	1	1
mol:cAMP	0.004	0.013	0.031	100	-10000	0	100
PTPN11	0.032	0.012	-10000	0	-10000	0	0
IL2RG	0.029	0.042	-10000	0	-0.42	4	4
actin cytoskeleton organization	-0.018	0.14	0.29	3	-0.34	46	49
GRB2	0.031	0.013	-10000	0	-10000	0	0
IL2	0.031	0.037	-10000	0	-0.42	3	3
PIK3CA	0.032	0.024	-10000	0	-0.42	1	1
Rac1/GTP	0.033	0.064	-10000	0	-0.22	17	17
LCK	-0.019	0.14	-10000	0	-0.42	54	54
BCL2	-0.18	0.38	-10000	0	-0.82	118	118

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.014	0.1	-9999	-0.26	58	58
E-cadherin/beta catenin	0.004	0.11	-9999	-0.3	55	55
CTNNB1	0.025	0.067	-9999	-0.42	11	11
JUP	0.028	0.042	-9999	-0.42	4	4
CDH1	-0.011	0.13	-9999	-0.42	45	45

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.06	0.29	-10000	0	-0.92	46	46
epithelial cell differentiation	-0.027	0.25	-10000	0	-0.72	48	48
ITCH	0.035	0.039	-10000	0	-0.11	6	6
WWP1	-0.087	0.39	-10000	0	-1.4	42	42
FYN	0.027	0.054	-10000	0	-0.42	7	7
EGFR	-0.015	0.13	-10000	0	-0.42	49	49
PRL	0.034	0.022	-10000	0	-0.42	1	1
neuron projection morphogenesis	-0.019	0.21	0.34	8	-0.64	43	51
PTPRZ1	0.023	0.061	-10000	0	-0.42	9	9
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.028	0.22	-10000	0	-0.71	43	43
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.064	0.25	-10000	0	-0.87	43	43
ADAM17	0.036	0.037	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.079	0.3	-10000	0	-1	45	45
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.062	0.29	-10000	0	-0.9	47	47
NCOR1	0.032	0.012	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.054	0.25	-10000	0	-0.82	43	43
GRIN2B	-0.062	0.22	0.25	1	-0.75	43	44
ErbB4/ErbB2/betacellulin	-0.069	0.26	-10000	0	-0.72	56	56
STAT1	0.02	0.075	-10000	0	-0.42	14	14
HBEGF	0.029	0.05	-10000	0	-0.42	6	6
PRLR	-0.001	0.12	-10000	0	-0.42	40	40
E4ICDs/ETO2	-0.1	0.32	-10000	0	-0.84	62	62
axon guidance	-0.068	0.28	-10000	0	-0.91	45	45
NEDD4	0.025	0.076	-10000	0	-0.42	11	11
Prolactin receptor/Prolactin receptor/Prolactin	0.022	0.094	-10000	0	-0.3	39	39
CBFA2T3	-0.047	0.16	-10000	0	-0.42	81	81
ErbB4/ErbB2/HBEGF	-0.05	0.26	-10000	0	-0.78	49	49
MAPK3	-0.016	0.22	0.35	8	-0.66	43	51
STAT1 (dimer)	-0.064	0.29	-10000	0	-0.9	47	47
MAPK1	-0.016	0.22	0.35	8	-0.66	43	51
JAK2	0.032	0.03	-10000	0	-0.42	2	2
ErbB4/ErbB2/neuregulin 1 beta	-0.063	0.25	-10000	0	-0.77	50	50
NRG1	0.013	0.021	-10000	0	-10000	0	0
NRG3	0.028	0.054	-10000	0	-0.42	7	7
NRG2	0.025	0.061	-10000	0	-0.42	9	9
NRG4	0.033	0.022	-10000	0	-0.42	1	1
heart development	-0.068	0.28	-10000	0	-0.91	45	45
neural crest cell migration	-0.062	0.25	-10000	0	-0.75	50	50
ERBB2	0.006	0.058	-10000	0	-0.3	15	15
WWOX/E4ICDs	-0.071	0.28	-10000	0	-0.92	46	46
SHC1	0.028	0.025	-10000	0	-0.42	1	1
ErbB4/EGFR/neuregulin 4	-0.065	0.28	-10000	0	-0.84	48	48
apoptosis	0.059	0.28	0.83	50	-10000	0	50
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.062	0.29	-10000	0	-0.91	47	47
ErbB4/ErbB2/epiregulin	-0.053	0.26	-10000	0	-0.77	50	50
ErbB4/ErbB4/betacellulin/betacellulin	-0.079	0.29	-10000	0	-0.85	53	53
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.031	0.28	-10000	0	-0.71	58	58
MDM2	-0.068	0.29	0.28	14	-0.92	45	59
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.044	0.23	-10000	0	-0.77	43	43
STAT5A	-0.041	0.28	0.33	7	-0.89	43	50
ErbB4/EGFR/neuregulin 1 beta	-0.07	0.25	-10000	0	-0.79	46	46
DLG4	0.032	0.012	-10000	0	-10000	0	0
GRB2/SHC	0.038	0.029	-10000	0	-0.3	1	1
E4ICDs/TAB2/NCoR1	-0.048	0.28	-10000	0	-0.86	46	46
STAT5A (dimer)	-0.019	0.28	-10000	0	-0.81	48	48
MAP3K7IP2	0.032	0.03	-10000	0	-0.42	2	2
STAT5B (dimer)	-0.045	0.28	-10000	0	-0.87	46	46
LRIG1	0.006	0.11	-10000	0	-0.42	31	31
EREG	0.025	0.051	-10000	0	-0.42	6	6
BTC	-0.009	0.13	-10000	0	-0.42	47	47
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.07	0.28	-10000	0	-0.92	45	45
ERBB4	-0.08	0.3	-10000	0	-1	45	45
STAT5B	0.03	0.024	-10000	0	-0.42	1	1
YAP1	-0.024	0.15	-10000	0	-0.41	48	48
GRB2	0.033	0.011	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.048	0.26	-10000	0	-0.76	50	50
glial cell differentiation	0.047	0.27	0.85	46	-10000	0	46
WWOX	0.027	0.016	-10000	0	-10000	0	0
cell proliferation	-0.077	0.26	0.34	1	-0.79	49	50

×

TCGA08_p53

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
CDKN2A	-0.002	0.05	-10000	0	-0.3	14	14
TP53	-0.025	0.091	0.26	1	-0.26	58	59
Senescence	-0.028	0.093	0.25	1	-0.25	66	67
Apoptosis	-0.028	0.093	0.25	1	-0.25	66	67
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.004	0.061	0.26	25	-10000	0	25
MDM4	0.026	0.032	-10000	0	-0.42	2	2

×

Canonical Wnt signaling pathway

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
HDAC1	0.053	0.052	0.23	21	-0.42	1	22
AES	0.052	0.042	0.2	22	-10000	0	22
FBXW11	0.033	0.029	-10000	0	-0.42	2	2
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
LRP6/FZD1	0.04	0.055	-10000	0	-0.3	12	12
SMAD4	0.029	0.054	-10000	0	-0.42	7	7
DKK2	0.006	0.11	-10000	0	-0.42	31	31
TLE1	0.022	0.12	0.22	21	-0.42	33	54
MACF1	0.035	0.021	-10000	0	-0.42	1	1
CTNNB1	-0.003	0.1	0.26	7	-0.37	11	18
WIF1	0.03	0.014	-10000	0	-10000	0	0
beta catenin/RanBP3	0.073	0.21	0.41	115	-0.36	7	122
KREMEN2	-0.09	0.19	-10000	0	-0.42	129	129
DKK1	-0.027	0.14	-10000	0	-0.42	60	60
beta catenin/beta TrCP1	0.011	0.11	0.28	5	-0.37	10	15
FZD1	0.028	0.057	-10000	0	-0.42	8	8
AXIN2	-0.047	0.4	0.6	52	-1.3	32	84
AXIN1	0.037	0.002	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.044	0.066	-10000	0	-0.59	4	4
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.008	0.17	0.3	7	-0.44	41	48
Axin1/APC/GSK3	0.033	0.051	0.32	1	-0.31	1	2
Axin1/APC/GSK3/beta catenin/Macf1	0.021	0.081	0.33	3	-0.36	5	8
HNF1A	0.017	0.045	0.18	22	-10000	0	22
CTBP1	0.05	0.046	0.23	18	-10000	0	18
MYC	0.028	0.47	0.59	112	-1.3	37	149
RANBP3	0.036	0.007	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.044	0.15	-10000	0	-0.26	154	154
NKD1	0.027	0.037	-10000	0	-0.42	3	3
TCF4	0.031	0.1	0.22	18	-0.4	22	40
TCF3	0.048	0.052	0.22	18	-0.42	2	20
WNT1/LRP6/FZD1/Axin1	0.076	0.058	-10000	0	-0.23	13	13
Ran/GTP	0.028	0.006	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.09	0.26	0.51	108	-0.47	12	120
LEF1	0.038	0.085	0.23	19	-0.4	13	32
DVL1	0.03	0.049	-10000	0	-0.28	3	3
CSNK2A1	0.035	0.006	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.045	0.19	-10000	0	-0.52	41	41
DKK1/LRP6/Kremen 2	-0.06	0.16	-10000	0	-0.27	169	169
LRP6	0.029	0.046	-10000	0	-0.42	5	5
CSNK1A1	0.053	0.048	0.24	19	-10000	0	19
NLK	0.029	0.026	-10000	0	-0.43	1	1
CCND1	-0.15	0.6	0.58	69	-1.4	86	155
WNT1	0.035	0.021	-10000	0	-0.42	1	1
GSK3A	0.036	0.005	-10000	0	-10000	0	0
GSK3B	0.036	0.005	-10000	0	-10000	0	0
FRAT1	0.029	0.054	-10000	0	-0.42	7	7
PPP2R5D	0.028	0.065	0.24	1	-0.29	14	15
APC	-0.012	0.059	0.2	18	-0.22	16	34
WNT1/LRP6/FZD1	0.022	0.051	-10000	0	-0.23	8	8
CREBBP	0.048	0.044	0.22	17	-10000	0	17

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.009	0.14	-9999	-0.42	51	51
SVIL	0.022	0.078	-9999	-0.42	15	15
ZNF318	0.033	0.006	-9999	-10000	0	0
JMJD2C	0.04	0.011	-9999	-10000	0	0
T-DHT/AR/Ubc9	-0.036	0.12	-9999	-0.25	106	106
CARM1	0.035	0.021	-9999	-0.42	1	1
PRDX1	0.033	0.036	-9999	-0.42	3	3
PELP1	0.032	0.011	-9999	-10000	0	0
CTNNB1	0.026	0.067	-9999	-0.42	11	11
AKT1	0.032	0.03	-9999	-0.42	2	2
PTK2B	0.028	0.016	-9999	-10000	0	0
MED1	-0.001	0	-9999	-10000	0	0
MAK	0.025	0.046	-9999	-0.42	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.037	0.005	-9999	-10000	0	0
GSN	0.023	0.078	-9999	-0.42	15	15
NCOA2	0.025	0.047	-9999	-0.42	5	5
NCOA6	0.037	0.007	-9999	-10000	0	0
DNA-PK	0.054	0.036	-9999	-0.26	2	2
NCOA4	0.03	0.05	-9999	-0.42	6	6
PIAS3	0.036	0.006	-9999	-10000	0	0
cell proliferation	-0.014	0.097	-9999	-0.56	13	13
XRCC5	0.035	0.004	-9999	-10000	0	0
UBE3A	0.036	0.029	-9999	-0.42	2	2
T-DHT/AR/SNURF	-0.051	0.12	-9999	-0.25	112	112
FHL2	-0.11	0.31	-9999	-0.9	65	65
RANBP9	0.036	0.008	-9999	-10000	0	0
JMJD1A	0.01	0.072	-9999	-0.15	86	86
CDK6	0.025	0.058	-9999	-0.42	8	8
TGFB1I1	0.018	0.085	-9999	-0.42	18	18
T-DHT/AR/CyclinD1	-0.073	0.17	-9999	-0.33	134	134
XRCC6	0.033	0.009	-9999	-10000	0	0
T-DHT/AR	-0.062	0.14	-9999	-0.22	210	210
CTDSP1	0.034	0.029	-9999	-0.42	2	2
CTDSP2	0.032	0.029	-9999	-0.42	2	2
BRCA1	0.023	0.07	-9999	-0.42	12	12
TCF4	0.014	0.093	-9999	-0.42	22	22
CDKN2A	0.015	0.075	-9999	-0.42	14	14
SRF	0.018	0.061	-9999	-0.14	60	60
NKX3-1	-0.047	0.1	-9999	-0.24	90	90
KLK3	0.021	0.054	-9999	-10000	0	0
TMF1	0.035	0.008	-9999	-10000	0	0
HNRNPA1	-0.001	0	-9999	-10000	0	0
AOF2	0.036	0.008	-9999	-10000	0	0
APPL1	0.004	0.02	-9999	-0.3	2	2
T-DHT/AR/Caspase 8	-0.038	0.13	-9999	-0.25	111	111
AR	-0.077	0.18	-9999	-0.43	100	100
UBA3	0	0	-9999	-10000	0	0
PATZ1	-0.001	0	-9999	-10000	0	0
PAWR	0.024	0.072	-9999	-0.42	13	13
PRKDC	0.029	0.031	-9999	-0.42	2	2
PA2G4	0.035	0.005	-9999	-10000	0	0
UBE2I	0.032	0.011	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.031	0.11	-9999	-0.23	106	106
RPS6KA3	0.034	0.041	-9999	-0.42	4	4
T-DHT/AR/ARA70	-0.041	0.13	-9999	-0.25	116	116
LATS2	0.024	0.061	-9999	-0.42	9	9
T-DHT/AR/PRX1	-0.035	0.12	-9999	-0.23	114	114
Cyclin D3/CDK11 p58	0.026	0.005	-9999	-10000	0	0
VAV3	-0.038	0.17	-9999	-0.42	81	81
KLK2	-0.012	0.087	-9999	-0.38	15	15
CASP8	0.036	0.004	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.021	0.12	-9999	-0.24	88	88
TMPRSS2	-0.15	0.35	-9999	-0.87	91	91
CCND1	-0.041	0.16	-9999	-0.42	79	79
PIAS1	0.037	0.007	-9999	-10000	0	0
mol:T-DHT	-0.013	0.03	-9999	-0.064	116	116
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.035	0.036	-9999	-0.42	3	3
T-DHT/AR/CDK6	-0.04	0.13	-9999	-0.25	116	116
CMTM2	0.029	0.025	-9999	-0.42	1	1
SNURF	0	0	-9999	-10000	0	0
ZMIZ1	-0.013	0.03	-9999	-0.065	116	116
CCND3	0.035	0.007	-9999	-10000	0	0
TGIF1	-0.001	0	-9999	-10000	0	0
FKBP4	0.031	0.046	-9999	-0.42	5	5

×

PLK2 and PLK4 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.005	0.12	-9999	-0.42	41	41
PLK4	0.03	0.05	-9999	-0.42	6	6
regulation of centriole replication	-0.013	0.091	-9999	-0.3	46	46

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.006	0.11	-10000	0	-0.3	52	52
EPHB2	0.032	0.03	-10000	0	-0.42	2	2
Syndecan-2/TACI	0.011	0.064	-10000	0	-0.24	28	28
LAMA1	0.034	0.009	-10000	0	-10000	0	0
Syndecan-2/alpha2 ITGB1	0.019	0.14	-10000	0	-0.25	86	86
HRAS	0.032	0.036	-10000	0	-0.42	3	3
Syndecan-2/CASK	-0.005	0.057	-10000	0	-0.24	28	28
ITGA5	0.034	0.029	-10000	0	-0.42	2	2
BAX	-0.008	0.052	-10000	0	-10000	0	0
EPB41	0.034	0.021	-10000	0	-0.42	1	1
positive regulation of cell-cell adhesion	0.008	0.065	-10000	0	-0.23	33	33
LAMA3	-0.019	0.14	-10000	0	-0.42	58	58
EZR	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.013	0.095	-10000	0	-0.42	23	23
Syndecan-2/MMP2	0	0.089	-10000	0	-0.29	40	40
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.015	0.1	-10000	0	-0.3	48	48
dendrite morphogenesis	0.012	0.065	-10000	0	-0.24	29	29
Syndecan-2/GM-CSF	0.011	0.066	-10000	0	-0.24	30	30
determination of left/right symmetry	-0.005	0.069	-10000	0	-0.29	28	28
Syndecan-2/PKC delta	0.012	0.067	-10000	0	-0.24	30	30
GNB2L1	0.034	0.035	-10000	0	-0.42	3	3
MAPK3	0.033	0.09	0.2	82	-0.22	27	109
MAPK1	0.037	0.095	0.2	94	-0.22	29	123
Syndecan-2/RACK1	0.025	0.067	-10000	0	-0.22	31	31
NF1	0.032	0.03	-10000	0	-0.42	2	2
FGFR/FGF/Syndecan-2	-0.005	0.069	-10000	0	-0.29	28	28
ITGA2	-0.01	0.13	-10000	0	-0.42	48	48
MAPK8	-0.005	0.059	-10000	0	-0.24	29	29
Syndecan-2/alpha2/beta1 Integrin	0.043	0.11	-10000	0	-0.24	50	50
Syndecan-2/Kininogen	0.013	0.065	-10000	0	-0.25	28	28
ITGB1	0.032	0.036	-10000	0	-0.42	3	3
SRC	0.037	0.093	0.19	88	-0.22	29	117
Syndecan-2/CASK/Protein 4.1	0.012	0.059	-10000	0	-0.22	29	29
extracellular matrix organization	0.013	0.065	-10000	0	-0.24	28	28
actin cytoskeleton reorganization	-0.006	0.1	-10000	0	-0.3	52	52
Syndecan-2/Caveolin-2/Ras	0.016	0.092	-10000	0	-0.27	41	41
Syndecan-2/Laminin alpha3	-0.013	0.1	-10000	0	-0.26	68	68
Syndecan-2/RasGAP	0.034	0.075	-10000	0	-0.21	35	35
alpha5/beta1 Integrin	0.048	0.037	-10000	0	-0.3	5	5
PRKCD	0.033	0.03	-10000	0	-0.42	2	2
Syndecan-2 dimer	0.012	0.066	-10000	0	-0.24	29	29
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	0.019	0.067	-10000	0	-0.21	33	33
RHOA	0.026	0.061	-10000	0	-0.42	9	9
SDCBP	0.023	0.058	-10000	0	-0.42	8	8
TNFRSF13B	0.032	0.012	-10000	0	-10000	0	0
RASA1	0.029	0.05	-10000	0	-0.42	6	6
alpha2/beta1 Integrin	0.015	0.1	-10000	0	-0.3	48	48
Syndecan-2/Synbindin	0.011	0.064	-10000	0	-0.24	28	28
TGFB1	0.035	0.021	-10000	0	-0.42	1	1
CASP3	0.034	0.093	0.2	88	-0.22	29	117
FN1	-0.01	0.14	-10000	0	-0.42	50	50
Syndecan-2/IL8	-0.007	0.094	-10000	0	-0.27	53	53
SDC2	-0.005	0.069	-10000	0	-0.29	28	28
KNG1	0.035	0.008	-10000	0	-10000	0	0
Syndecan-2/Neurofibromin	0.011	0.067	-10000	0	-0.25	30	30
TRAPPC4	0.032	0.012	-10000	0	-10000	0	0
CSF2	0.031	0.036	-10000	0	-0.42	3	3
Syndecan-2/TGFB1	0.013	0.065	-10000	0	-0.25	28	28
Syndecan-2/Syntenin/PI-4-5-P2	0.009	0.065	-10000	0	-0.23	33	33
Syndecan-2/Ezrin	0.009	0.064	-10000	0	-0.22	34	34
PRKACA	0.036	0.095	0.2	93	-0.22	30	123
angiogenesis	-0.007	0.094	-10000	0	-0.27	53	53
MMP2	0.005	0.1	-10000	0	-0.42	27	27
IL8	-0.004	0.12	-10000	0	-0.42	37	37
calcineurin-NFAT signaling pathway	0.011	0.064	-10000	0	-0.24	28	28

×

Signaling events mediated by PTP1B

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
PDGFRB	0.028	0.057	-10000	0	-0.42	8	8
Jak2/Leptin Receptor	-0.035	0.14	-10000	0	-0.39	41	41
PTP1B/AKT1	-0.045	0.14	0.26	3	-0.31	70	73
FYN	0.027	0.054	-10000	0	-0.42	7	7
p210 bcr-abl/PTP1B	-0.062	0.14	0.28	3	-0.33	73	76
EGFR	-0.024	0.14	-10000	0	-0.43	49	49
EGF/EGFR	-0.091	0.18	0.29	2	-0.32	158	160
CSF1	0.034	0.021	-10000	0	-0.42	1	1
AKT1	0.033	0.03	-10000	0	-0.43	2	2
INSR	0.034	0.029	-10000	0	-0.42	2	2
PTP1B/N-cadherin	-0.056	0.15	0.3	2	-0.35	69	71
Insulin Receptor/Insulin	-0.008	0.13	0.31	2	-0.33	39	41
HCK	0.018	0.087	-10000	0	-0.42	19	19
CRK	0.032	0.023	-10000	0	-0.42	1	1
TYK2	-0.061	0.14	0.3	4	-0.33	68	72
EGF	-0.073	0.19	-10000	0	-0.43	110	110
YES1	0.029	0.05	-10000	0	-0.42	6	6
CAV1	-0.071	0.15	0.27	3	-0.34	79	82
TXN	0.033	0.007	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.056	0.16	0.3	2	-0.33	87	89
cell migration	0.062	0.14	0.33	73	-0.28	3	76
STAT3	0.028	0.032	-10000	0	-0.42	2	2
PRLR	0.001	0.12	-10000	0	-0.4	42	42
ITGA2B	0.033	0.01	-10000	0	-10000	0	0
CSF1R	0.035	0.006	-10000	0	-10000	0	0
Prolactin Receptor/Prolactin	0.028	0.098	-10000	0	-0.3	41	41
FGR	0.035	0.008	-10000	0	-10000	0	0
PTP1B/p130 Cas	-0.045	0.14	0.3	1	-0.33	67	68
Crk/p130 Cas	-0.038	0.14	0.3	1	-0.33	62	63
DOK1	-0.054	0.14	0.26	3	-0.38	53	56
JAK2	-0.043	0.14	-10000	0	-0.4	41	41
Jak2/Leptin Receptor/Leptin	-0.038	0.14	0.25	1	-0.39	38	39
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
PTPN1	-0.062	0.14	0.28	3	-0.34	73	76
LYN	0.03	0.014	-10000	0	-10000	0	0
CDH2	0.013	0.091	-10000	0	-0.42	21	21
SRC	-0.003	0.12	-10000	0	-0.63	14	14
ITGB3	0.028	0.046	-10000	0	-0.42	5	5
CAT1/PTP1B	-0.085	0.2	0.32	2	-0.46	77	79
CAPN1	0.025	0.065	-10000	0	-0.43	10	10
CSK	0.034	0.022	-10000	0	-0.42	1	1
PI3K	-0.003	0.14	0.28	2	-0.34	42	44
mol:H2O2	-0.001	0.006	-10000	0	-10000	0	0
STAT3 (dimer)	-0.033	0.14	-10000	0	-0.37	36	36
negative regulation of transcription	-0.042	0.14	-10000	0	-0.4	41	41
FCGR2A	0.018	0.07	-10000	0	-0.42	12	12
FER	0.032	0.022	-10000	0	-0.43	1	1
alphaIIb/beta3 Integrin	0.044	0.035	-10000	0	-0.31	4	4
BLK	0.022	0.038	-10000	0	-0.42	3	3
Insulin Receptor/Insulin/Shc	0.053	0.04	-10000	0	-0.26	3	3
RHOA	0.025	0.062	-10000	0	-0.43	9	9
LEPR	0.026	0.058	-10000	0	-0.42	8	8
BCAR1	0.03	0.014	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.033	0.01	-10000	0	-10000	0	0
mol:NADPH	-0.002	0.004	-10000	0	-10000	0	0
TRPV6	-0.068	0.21	0.26	1	-0.5	70	71
PRL	0.036	0.026	-10000	0	-0.26	3	3
SOCS3	0.006	0.19	-10000	0	-1.3	10	10
SPRY2	0.005	0.11	-10000	0	-0.43	29	29
Insulin Receptor/Insulin/IRS1	0.032	0.11	-10000	0	-0.27	55	55
CSF1/CSF1R	-0.035	0.15	0.3	2	-0.33	62	64
Ras protein signal transduction	0.055	0.17	0.62	39	-10000	0	39
IRS1	-0.014	0.14	-10000	0	-0.42	54	54
INS	0.034	0.022	-10000	0	-0.43	1	1
LEP	0.001	0.11	-10000	0	-0.42	32	32
STAT5B	-0.052	0.14	0.25	2	-0.34	61	63
STAT5A	-0.054	0.14	0.25	2	-0.34	64	66
GRB2	0.033	0.011	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.05	0.15	0.3	2	-0.34	73	75
CSN2	0.022	0.11	-10000	0	-1.4	2	2
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
LAT	-0.009	0.12	-10000	0	-0.53	19	19
YBX1	0.037	0.043	-10000	0	-0.38	5	5
LCK	-0.017	0.14	-10000	0	-0.42	54	54
SHC1	0.028	0.025	-10000	0	-0.42	1	1
NOX4	-0.023	0.15	-10000	0	-0.43	58	58

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.025	0.025	-10000	0	-0.3	3	3
alphaV beta3 Integrin	0.031	0.1	-10000	0	-0.26	51	51
PTK2	0.01	0.12	0.36	5	-0.42	18	23
IGF1R	-0.042	0.17	-10000	0	-0.42	84	84
PI4KB	0	0	-10000	0	-10000	0	0
MFGE8	0.017	0.085	-10000	0	-0.42	18	18
SRC	0.033	0.029	-10000	0	-0.42	2	2
CDKN1B	-0.008	0.12	-10000	0	-0.46	29	29
VEGFA	0	0	-10000	0	-10000	0	0
ILK	0.015	0.063	-10000	0	-0.48	5	5
ROCK1	0.036	0.006	-10000	0	-10000	0	0
AKT1	0.002	0.073	0.21	3	-0.31	17	20
PTK2B	0.006	0.059	0.21	9	-0.24	20	29
alphaV/beta3 Integrin/JAM-A	0.058	0.1	-10000	0	-0.23	42	42
CBL	0.032	0.012	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.051	0.073	-10000	0	-0.27	23	23
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.037	0.19	-10000	0	-0.31	151	151
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.006	0.07	-10000	0	-0.23	27	27
alphaV/beta3 Integrin/Syndecan-1	0.029	0.11	-10000	0	-0.27	56	56
PI4KA	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.079	0.21	-10000	0	-0.32	191	191
PI4 Kinase	0	0	-10000	0	-10000	0	0
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
alphaV/beta3 Integrin/Osteopontin	-0.019	0.15	-10000	0	-0.27	124	124
RPS6KB1	-0.12	0.17	0.52	1	-0.44	78	79
TLN1	0.035	0.021	-10000	0	-0.42	1	1
MAPK3	-0.045	0.19	-10000	0	-0.56	50	50
GPR124	0.017	0.073	-10000	0	-0.42	13	13
MAPK1	-0.049	0.2	-10000	0	-0.54	58	58
PXN	0.036	0.004	-10000	0	-10000	0	0
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
alphaV/beta3 Integrin/Tumstatin	0.053	0.073	-10000	0	-0.28	21	21
cell adhesion	0.024	0.1	-10000	0	-0.27	47	47
ANGPTL3	0.031	0.041	-10000	0	-0.42	4	4
VEGFR2 homodimer/VEGFA homodimer/Src	0.044	0.029	-10000	0	-0.25	4	4
IGF-1R heterotetramer	-0.042	0.17	-10000	0	-0.42	84	84
Rac1/GDP	0.026	0.004	-10000	0	-10000	0	0
TGFBR2	0.033	0.036	-10000	0	-0.42	3	3
ITGB3	0.029	0.046	-10000	0	-0.42	5	5
IGF1	-0.038	0.16	-10000	0	-0.42	78	78
RAC1	0.035	0.006	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.035	0.086	-10000	0	-0.3	26	26
apoptosis	0.022	0.077	-10000	0	-0.42	15	15
CD47	0.019	0.085	-10000	0	-0.42	18	18
alphaV/beta3 Integrin/CD47	0.042	0.089	-10000	0	-0.26	37	37
VCL	0.035	0.021	-10000	0	-0.42	1	1
alphaV/beta3 Integrin/Del1	-0.009	0.14	-10000	0	-0.28	104	104
CSF1	0.034	0.021	-10000	0	-0.42	1	1
PIK3C2A	0.011	0.08	-10000	0	-0.54	8	8
PI4 Kinase/Pyk2	0.004	0.075	-10000	0	-0.21	50	50
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.051	0.067	-10000	0	-0.25	20	20
FAK1/Vinculin	0.026	0.12	0.35	5	-0.34	18	23
alphaV beta3/Integrin/ppsTEM5	0.035	0.086	-10000	0	-0.3	26	26
RHOA	0.026	0.061	-10000	0	-0.42	9	9
VTN	0.035	0.008	-10000	0	-10000	0	0
BCAR1	0.03	0.014	-10000	0	-10000	0	0
FGF2	-0.001	0.11	-10000	0	-0.42	34	34
F11R	-0.005	0.072	-10000	0	-0.3	28	28
alphaV/beta3 Integrin/Lactadherin	0.044	0.092	-10000	0	-0.31	27	27
alphaV/beta3 Integrin/TGFBR2	0.052	0.071	-10000	0	-0.27	21	21
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.06	0.066	-10000	0	-0.23	15	15
HSP90AA1	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.051	0.063	-10000	0	-0.24	20	20
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.01	0.14	-10000	0	-0.42	50	50
alphaV/beta3 Integrin/Pyk2	0.035	0.065	-10000	0	-0.24	20	20
SDC1	-0.003	0.13	-10000	0	-0.42	42	42
VAV3	-0.05	0.087	0.18	1	-0.24	83	84
PTPN11	0.036	0.004	-10000	0	-10000	0	0
IRS1	-0.014	0.14	-10000	0	-0.42	54	54
FAK1/Paxillin	0.025	0.12	0.35	5	-0.34	18	23
cell migration	0.019	0.11	0.32	6	-0.32	16	22
ITGAV	0.022	0.078	-10000	0	-0.42	15	15
PI3K	0.058	0.11	-10000	0	-0.22	50	50
SPP1	-0.073	0.19	-10000	0	-0.42	115	115
KDR	0.033	0.035	-10000	0	-0.42	3	3
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.022	0.077	-10000	0	-0.42	15	15
COL4A3	0.033	0.036	-10000	0	-0.42	3	3
angiogenesis	-0.036	0.2	-10000	0	-0.56	52	52
Rac1/GTP	-0.012	0.097	-10000	0	-0.22	86	86
EDIL3	-0.056	0.18	-10000	0	-0.42	97	97
cell proliferation	0.052	0.071	-10000	0	-0.27	21	21

×

Cellular roles of Anthrax toxin

Figure S44. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S44. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.006	0.11	-10000	0	-0.42	32	32
ANTXR2	0.022	0.078	-10000	0	-0.42	15	15
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.006	0.017	-10000	0	-0.063	40	40
monocyte activation	-0.017	0.12	-10000	0	-0.37	56	56
MAP2K2	0.004	0.1	-10000	0	-0.63	12	12
MAP2K1	-0.009	0.015	-10000	0	-0.089	5	5
MAP2K7	-0.009	0.018	-10000	0	-0.11	7	7
MAP2K6	-0.013	0.041	0.13	3	-0.21	17	20
CYAA	-0.025	0.066	-10000	0	-0.24	40	40
MAP2K4	-0.008	0.018	-10000	0	-0.12	5	5
IL1B	-0.026	0.07	0.16	2	-0.21	54	56
Channel	0.021	0.085	-10000	0	-0.26	40	40
NLRP1	-0.006	0.016	-10000	0	-0.058	40	40
CALM1	0.035	0.007	-10000	0	-10000	0	0
negative regulation of phagocytosis	0	0.074	-10000	0	-0.43	13	13
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.006	0.017	0.063	40	-10000	0	40
MAPK3	-0.007	0.023	0.13	6	-0.11	6	12
MAPK1	-0.009	0.018	-10000	0	-0.11	7	7
PGR	-0.074	0.1	-10000	0	-0.22	169	169
PA/Cellular Receptors	0.021	0.093	-10000	0	-0.28	40	40
apoptosis	-0.006	0.017	-10000	0	-0.063	40	40
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.021	0.081	-10000	0	-0.24	40	40
macrophage activation	0.001	0.051	0.17	35	-0.2	2	37
TNF	0.026	0.061	-10000	0	-0.42	9	9
VCAM1	-0.018	0.13	-10000	0	-0.37	56	56
platelet activation	0	0.074	-10000	0	-0.43	13	13
MAPKKK cascade	0.001	0.032	0.12	6	-0.089	14	20
IL18	-0.02	0.064	0.14	1	-0.24	34	35
negative regulation of macrophage activation	-0.006	0.017	-10000	0	-0.063	40	40
LEF	-0.006	0.017	-10000	0	-0.063	40	40
CASP1	-0.008	0.031	-10000	0	-0.085	61	61
mol:cAMP	0	0.075	-10000	0	-0.44	13	13
necrosis	-0.006	0.017	-10000	0	-0.063	40	40
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.021	0.08	-10000	0	-0.24	40	40
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.018	0.11	-10000	0	-0.31	43	43
alphaM/beta2 Integrin/GPIbA	0.035	0.084	-10000	0	-0.29	22	22
alphaM/beta2 Integrin/proMMP-9	0.01	0.12	-10000	0	-0.29	60	60
PLAUR	0.009	0.11	-10000	0	-0.42	29	29
HMGB1	0.025	0.031	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.037	0.087	-10000	0	-0.3	23	23
AGER	0.025	0.037	-10000	0	-0.42	1	1
RAP1A	0.031	0.045	-10000	0	-0.42	5	5
SELPLG	0.025	0.07	-10000	0	-0.42	12	12
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.043	0.12	-10000	0	-0.24	56	56
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	-0.013	0.14	-10000	0	-0.42	52	52
CYR61	-0.004	0.12	-10000	0	-0.42	40	40
TLN1	0.035	0.021	-10000	0	-0.42	1	1
Rap1/GTP	0.011	0.13	-10000	0	-0.36	35	35
RHOA	0.026	0.061	-10000	0	-0.42	9	9
P-selectin oligomer	-0.039	0.16	-10000	0	-0.42	73	73
MYH2	-0.016	0.14	0.23	1	-0.42	33	34
MST1R	-0.005	0.13	-10000	0	-0.42	44	44
leukocyte activation during inflammatory response	0.041	0.079	-10000	0	-0.25	23	23
APOB	0.036	0.004	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.005	0.1	-10000	0	-0.42	27	27
JAM3	0.014	0.087	-10000	0	-0.42	19	19
GP1BA	0.03	0.014	-10000	0	-10000	0	0
alphaM/beta2 Integrin/CTGF	0.018	0.12	-10000	0	-0.32	45	45
alphaM/beta2 Integrin	-0.01	0.13	-10000	0	-0.38	37	37
JAM3 homodimer	0.014	0.087	-10000	0	-0.42	19	19
ICAM2	0.027	0.046	-10000	0	-0.42	5	5
ICAM1	0.018	0.085	-10000	0	-0.42	18	18
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.009	0.13	-10000	0	-0.38	37	37
cell adhesion	0.034	0.083	-10000	0	-0.29	22	22
NFKB1	0	0.15	0.39	1	-0.37	52	53
THY1	0.015	0.085	-10000	0	-0.42	18	18
RhoA/GDP	0.02	0.043	-10000	0	-0.3	9	9
Lipoprotein(a)	0.045	0.019	-10000	0	-0.25	1	1
alphaM/beta2 Integrin/LRP/tPA	0.016	0.12	-10000	0	-0.26	61	61
IL6	-0.049	0.23	0.36	2	-0.6	65	67
ITGB2	0.006	0.098	-10000	0	-0.44	21	21
elevation of cytosolic calcium ion concentration	0.015	0.15	-10000	0	-0.35	61	61
alphaM/beta2 Integrin/JAM2/JAM3	0.026	0.13	-10000	0	-0.31	48	48
JAM2	0.012	0.099	-10000	0	-0.42	25	25
alphaM/beta2 Integrin/ICAM1	0.04	0.13	-10000	0	-0.27	64	64
alphaM/beta2 Integrin/uPA/Plg	0.026	0.13	-10000	0	-0.28	58	58
RhoA/GTP	-0.03	0.14	-10000	0	-0.44	37	37
positive regulation of phagocytosis	0.004	0.14	-10000	0	-0.41	36	36
Ron/MSP	0.02	0.1	-10000	0	-0.3	44	44
alphaM/beta2 Integrin/uPAR/uPA	0.017	0.15	-10000	0	-0.35	61	61
alphaM/beta2 Integrin/uPAR	0.024	0.11	-10000	0	-0.33	39	39
PLAU	-0.013	0.14	-10000	0	-0.42	52	52
PLAT	-0.021	0.14	-10000	0	-0.42	51	51
actin filament polymerization	-0.013	0.14	0.24	3	-0.4	33	36
MST1	0.034	0.008	-10000	0	-10000	0	0
alphaM/beta2 Integrin/lipoprotein(a)	0.047	0.083	-10000	0	-0.25	23	23
TNF	-0.015	0.16	0.35	2	-0.41	51	53
RAP1B	0.033	0.03	-10000	0	-0.42	2	2
alphaM/beta2 Integrin/uPA	0.013	0.13	-10000	0	-0.31	56	56
fibrinolysis	0.024	0.12	-10000	0	-0.28	58	58
HCK	0.018	0.087	-10000	0	-0.42	19	19
dendritic cell antigen processing and presentation	-0.009	0.13	-10000	0	-0.38	37	37
VTN	0.035	0.008	-10000	0	-10000	0	0
alphaM/beta2 Integrin/CYR61	0.019	0.12	-10000	0	-0.3	47	47
LPA	0.033	0.022	-10000	0	-0.42	1	1
LRP1	0.035	0.021	-10000	0	-0.42	1	1
cell migration	-0.011	0.13	-10000	0	-0.28	76	76
FN1	-0.01	0.14	-10000	0	-0.42	50	50
alphaM/beta2 Integrin/Thy1	0.024	0.1	-10000	0	-0.29	37	37
MPO	0.032	0.013	-10000	0	-10000	0	0
KNG1	0.035	0.008	-10000	0	-10000	0	0
RAP1/GDP	0.041	0.037	-10000	0	-0.25	7	7
ROCK1	-0.019	0.14	-10000	0	-0.42	37	37
ELA2	0.035	0.008	-10000	0	-10000	0	0
PLG	0.032	0.03	-10000	0	-0.42	2	2
CTGF	0.002	0.11	-10000	0	-0.42	34	34
alphaM/beta2 Integrin/Hck	0.03	0.11	-10000	0	-0.37	28	28
ITGAM	0.022	0.053	-10000	0	-0.43	5	5
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.003	0.14	-10000	0	-0.28	77	77
HP	0.027	0.037	-10000	0	-0.42	3	3
leukocyte adhesion	0	0.15	-10000	0	-0.4	42	42
SELP	-0.039	0.16	-10000	0	-0.42	73	73

×

Reelin signaling pathway

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
CDK5R1/CDK5	0.048	0.017	-10000	0	-10000	0	0
VLDLR	-0.007	0.12	-10000	0	-0.42	42	42
CRKL	0.031	0.041	-10000	0	-0.42	4	4
LRPAP1	0.035	0.007	-10000	0	-10000	0	0
FYN	0.027	0.054	-10000	0	-0.42	7	7
ITGA3	0.023	0.07	-10000	0	-0.42	12	12
RELN/VLDLR/Fyn	0.027	0.1	-10000	0	-0.27	51	51
MAPK8IP1/MKK7/MAP3K11/JNK1	0.07	0.07	-10000	0	-0.22	15	15
AKT1	-0.017	0.088	-10000	0	-0.23	57	57
MAP2K7	0.035	0.021	-10000	0	-0.42	1	1
RAPGEF1	0.036	0.004	-10000	0	-10000	0	0
DAB1	0.035	0.007	-10000	0	-10000	0	0
RELN/LRP8/DAB1	0.039	0.081	-10000	0	-0.23	40	40
LRPAP1/LRP8	0.024	0.089	-10000	0	-0.3	35	35
RELN/LRP8/DAB1/Fyn	0.045	0.09	-10000	0	-0.22	46	46
DAB1/alpha3/beta1 Integrin	0.016	0.12	-10000	0	-0.22	85	85
long-term memory	0.049	0.1	-10000	0	-0.22	55	55
DAB1/LIS1	0.032	0.12	-10000	0	-0.22	80	80
DAB1/CRLK/C3G	0.021	0.11	-10000	0	-0.22	82	82
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
DAB1/NCK2	0.039	0.12	-10000	0	-0.22	80	80
ARHGEF2	0.022	0.055	-10000	0	-0.42	7	7
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.033	0.011	-10000	0	-10000	0	0
CDK5R1	0.033	0.01	-10000	0	-10000	0	0
RELN	0.03	0.046	-10000	0	-0.42	5	5
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
RELN/LRP8/Fyn	0.031	0.096	-10000	0	-0.26	46	46
GRIN2A/RELN/LRP8/DAB1/Fyn	0.056	0.094	-10000	0	-0.22	41	41
MAPK8	0.033	0.035	-10000	0	-0.42	3	3
RELN/VLDLR/DAB1	0.032	0.088	-10000	0	-0.23	46	46
ITGB1	0.032	0.036	-10000	0	-0.42	3	3
MAP1B	-0.027	0.12	0.32	5	-0.25	96	101
RELN/LRP8	0.039	0.089	-10000	0	-0.25	40	40
GRIN2B/RELN/LRP8/DAB1/Fyn	0.047	0.11	-10000	0	-0.23	61	61
PI3K	0.036	0.065	-10000	0	-0.3	17	17
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.04	0.059	-10000	0	-0.32	12	12
RAP1A	-0.042	0.097	0.34	7	-0.43	3	10
PAFAH1B1	0.032	0.023	-10000	0	-0.42	1	1
MAPK8IP1	0.034	0.029	-10000	0	-0.42	2	2
CRLK/C3G	0.047	0.034	-10000	0	-0.3	4	4
GRIN2B	0.018	0.082	-10000	0	-0.42	17	17
NCK2	0.036	0.005	-10000	0	-10000	0	0
neuron differentiation	0.018	0.083	-10000	0	-0.32	9	9
neuron adhesion	-0.041	0.11	0.35	7	-0.39	6	13
LRP8	-0.001	0.12	-10000	0	-0.42	35	35
GSK3B	-0.015	0.092	0.19	5	-0.23	55	60
RELN/VLDLR/DAB1/Fyn	0.039	0.097	-10000	0	-0.23	51	51
MAP3K11	0.034	0.029	-10000	0	-0.42	2	2
RELN/VLDLR/DAB1/P13K	-0.007	0.095	-10000	0	-0.24	60	60
CDK5	0.035	0.007	-10000	0	-10000	0	0
MAPT	-0.068	0.18	0.77	6	-0.38	96	102
neuron migration	-0.024	0.12	0.3	11	-0.33	18	29
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.017	0.082	-10000	0	-0.32	9	9
RELN/VLDLR	0.025	0.12	-10000	0	-0.24	80	80

×

TCGA08_retinoblastoma

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
CDKN2B	0.021	0.068	-10000	0	-0.39	12	12
CDKN2C	0.024	0.064	-10000	0	-0.37	12	12
CDKN2A	0.019	0.071	-10000	0	-0.39	14	14
CCND2	0.003	0.047	0.18	27	-0.13	2	29
RB1	-0.011	0.062	0.24	2	-0.21	38	40
CDK4	0.007	0.057	0.22	30	-10000	0	30
CDK6	0.004	0.058	0.21	28	-0.17	6	34
G1/S progression	0.018	0.073	0.2	57	-0.26	3	60

×

Caspase cascade in apoptosis

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
TOP1	-0.005	0.11	0.24	1	-0.46	10	11
ACTA1	-0.016	0.12	0.23	12	-0.31	44	56
NUMA1	-0.014	0.12	-10000	0	-0.42	16	16
SPTAN1	-0.021	0.12	0.24	8	-0.31	47	55
LIMK1	-0.033	0.13	0.24	3	-0.33	49	52
BIRC3	-0.008	0.12	-10000	0	-0.42	40	40
BIRC2	0.032	0.012	-10000	0	-10000	0	0
BAX	0.035	0.007	-10000	0	-10000	0	0
CASP10	-0.048	0.091	-10000	0	-0.26	75	75
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	-0.011	0.12	0.26	1	-0.49	12	13
DIABLO	0.036	0.004	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.02	0.12	0.24	8	-0.3	47	55
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.03	0.05	-10000	0	-0.42	6	6
GSN	-0.028	0.12	0.26	5	-0.32	51	56
MADD	0.036	0.005	-10000	0	-10000	0	0
TFAP2A	-0.003	0.16	-10000	0	-0.58	32	32
BID	-0.022	0.069	-10000	0	-0.17	82	82
MAP3K1	-0.034	0.14	-10000	0	-0.43	49	49
TRADD	0.03	0.014	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.047	0.037	-10000	0	-0.3	5	5
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.03	0.13	0.3	6	-0.33	51	57
CASP9	0.034	0.022	-10000	0	-0.42	1	1
DNA repair	-0.022	0.069	0.28	9	-0.18	18	27
neuron apoptosis	-0.031	0.2	-10000	0	-0.67	41	41
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.018	0.12	0.25	1	-0.39	20	21
APAF1	0.032	0.041	-10000	0	-0.42	4	4
CASP6	-0.014	0.15	-10000	0	-0.79	15	15
TRAF2	0.034	0.029	-10000	0	-0.42	2	2
ICAD/CAD	-0.024	0.11	0.24	4	-0.31	45	49
CASP7	0.031	0.1	0.25	45	-0.32	14	59
KRT18	-0.066	0.22	-10000	0	-0.57	73	73
apoptosis	-0.016	0.12	0.26	3	-0.37	24	27
DFFA	-0.023	0.12	0.23	5	-0.31	46	51
DFFB	-0.023	0.12	0.24	4	-0.31	46	50
PARP1	0.022	0.07	0.18	18	-0.28	9	27
actin filament polymerization	0.033	0.13	0.32	46	-0.29	7	53
TNF	0.026	0.061	-10000	0	-0.42	9	9
CYCS	-0.008	0.057	0.15	3	-0.21	10	13
SATB1	-0.028	0.16	-10000	0	-0.71	16	16
SLK	-0.023	0.12	0.23	5	-0.3	48	53
p15 BID/BAX	-0.002	0.077	-10000	0	-0.25	14	14
CASP2	-0.016	0.1	0.22	4	-0.32	29	33
JNK cascade	0.034	0.14	0.42	49	-10000	0	49
CASP3	-0.021	0.12	0.22	8	-0.32	50	58
LMNB2	-0.009	0.12	-10000	0	-0.45	18	18
RIPK1	0.035	0.007	-10000	0	-10000	0	0
CASP4	0.023	0.061	-10000	0	-0.42	9	9
Mammalian IAPs/DIABLO	0.034	0.082	-10000	0	-0.23	39	39
negative regulation of DNA binding	-0.002	0.16	-10000	0	-0.57	33	33
stress fiber formation	-0.022	0.12	0.23	5	-0.3	46	51
GZMB	-0.033	0.12	-10000	0	-0.31	75	75
CASP1	-0.008	0.1	-10000	0	-0.36	32	32
LMNB1	-0.06	0.16	0.25	1	-0.39	46	47
APP	-0.031	0.2	-10000	0	-0.68	41	41
TNFRSF1A	0.033	0.022	-10000	0	-0.42	1	1
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.009	0.001	-10000	0	-10000	0	0
VIM	-0.012	0.13	0.27	3	-0.38	24	27
LMNA	-0.008	0.099	0.25	1	-0.31	22	23
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.016	0.11	-10000	0	-0.34	32	32
LRDD	0.035	0.008	-10000	0	-10000	0	0
SREBF1	-0.036	0.13	0.25	3	-0.32	49	52
APAF-1/Caspase 9	0.016	0.11	-10000	0	-0.64	12	12
nuclear fragmentation during apoptosis	-0.013	0.12	-10000	0	-0.42	16	16
CFL2	-0.034	0.13	0.29	7	-0.33	46	53
GAS2	-0.031	0.13	0.24	5	-0.32	52	57
positive regulation of apoptosis	-0.028	0.12	0.26	1	-0.37	27	28
PRF1	0.027	0.054	-10000	0	-0.42	7	7

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.035	0.036	-10000	0	-0.41	2	2
HSPA8	0.018	0.073	-10000	0	-0.42	13	13
SMAD3/SMAD4/ER alpha	-0.034	0.18	-10000	0	-0.29	135	135
AKT1	0.03	0.038	-10000	0	-0.42	2	2
GSC	-0.19	0.49	-10000	0	-1.4	74	74
NKX2-5	0.028	0.022	-10000	0	-10000	0	0
muscle cell differentiation	0.012	0.17	0.39	52	-10000	0	52
SMAD2-3/SMAD4/SP1	0.022	0.18	-10000	0	-0.36	62	62
SMAD4	-0.004	0.097	-10000	0	-0.24	43	43
CBFB	0.03	0.014	-10000	0	-10000	0	0
SAP18	0.033	0.01	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.062	0.049	-10000	0	-0.23	4	4
SMAD3/SMAD4/VDR	0.059	0.12	-10000	0	-0.26	32	32
MYC	-0.001	0.1	-10000	0	-0.41	29	29
CDKN2B	-0.1	0.32	-10000	0	-1.1	35	35
AP1	-0.03	0.18	-10000	0	-0.38	84	84
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.007	0.099	-10000	0	-0.35	18	18
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.007	0.092	-10000	0	-0.27	43	43
SP3	0.028	0.03	-10000	0	-10000	0	0
CREB1	0.035	0.021	-10000	0	-0.42	1	1
FOXH1	0.013	0.059	-10000	0	-0.18	11	11
SMAD3/SMAD4/GR	0.027	0.12	-10000	0	-0.28	43	43
GATA3	-0.044	0.17	-10000	0	-0.41	91	91
SKI/SIN3/HDAC complex/NCoR1	0.015	0.073	-10000	0	-0.31	12	12
MEF2C/TIF2	-0.014	0.13	0.33	1	-0.37	39	40
endothelial cell migration	0.005	0.24	1.2	17	-10000	0	17
MAX	0.035	0.011	-10000	0	-10000	0	0
RBBP7	0.034	0.029	-10000	0	-0.42	2	2
RBBP4	0.034	0.021	-10000	0	-0.42	1	1
RUNX2	0.031	0.041	-10000	0	-0.42	4	4
RUNX3	-0.01	0.13	-10000	0	-0.42	46	46
RUNX1	0.008	0.11	-10000	0	-0.42	29	29
CTBP1	0.035	0.008	-10000	0	-10000	0	0
NR3C1	0.024	0.072	-10000	0	-0.42	13	13
VDR	0.02	0.082	-10000	0	-0.42	17	17
CDKN1A	-0.042	0.24	-10000	0	-1.2	17	17
KAT2B	0.001	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.015	0.14	-10000	0	-0.28	86	86
DCP1A	0.034	0.022	-10000	0	-0.42	1	1
SKI	0.036	0.002	-10000	0	-10000	0	0
SERPINE1	-0.006	0.25	-10000	0	-1.2	17	17
SMAD3/SMAD4/ATF2	0.034	0.11	-10000	0	-0.26	33	33
SMAD3/SMAD4/ATF3	0.015	0.12	-10000	0	-0.3	43	43
SAP30	0.03	0.046	-10000	0	-0.42	5	5
Cbp/p300/PIAS3	0.067	0.051	0.22	2	-0.26	1	3
JUN	-0.043	0.18	-10000	0	-0.42	69	69
SMAD3/SMAD4/IRF7	0.032	0.12	-10000	0	-0.28	41	41
TFE3	0.033	0.035	-10000	0	-0.15	5	5
COL1A2	-0.076	0.33	-10000	0	-0.87	70	70
mesenchymal cell differentiation	-0.03	0.11	0.28	33	-10000	0	33
DLX1	0.033	0.011	-10000	0	-10000	0	0
TCF3	0.033	0.03	-10000	0	-0.42	2	2
FOS	-0.038	0.16	-10000	0	-0.45	66	66
SMAD3/SMAD4/Max	0.033	0.11	-10000	0	-0.26	32	32
Cbp/p300/SNIP1	0.06	0.045	-10000	0	-0.26	4	4
ZBTB17	0.035	0.013	-10000	0	-10000	0	0
LAMC1	-0.007	0.11	-10000	0	-0.4	26	26
TGIF2/HDAC complex/SMAD3/SMAD4	0.028	0.11	-10000	0	-0.27	37	37
IRF7	0.028	0.059	-10000	0	-0.42	8	8
ESR1	-0.082	0.19	-10000	0	-0.41	132	132
HNF4A	0.033	0.03	-10000	0	-0.42	2	2
MEF2C	-0.03	0.14	0.34	3	-0.38	45	48
SMAD2-3/SMAD4	0.018	0.13	-10000	0	-0.27	48	48
Cbp/p300/Src-1	0.062	0.049	-10000	0	-0.23	5	5
IGHV3OR16-13	-0.003	0.065	-10000	0	-0.44	8	8
TGIF2/HDAC complex	0.029	0.05	-10000	0	-0.42	6	6
CREBBP	0.034	0.019	-10000	0	-10000	0	0
SKIL	0.028	0.05	-10000	0	-0.42	6	6
HDAC1	0.034	0.021	-10000	0	-0.42	1	1
HDAC2	0.032	0.023	-10000	0	-0.42	1	1
SNIP1	0.032	0.036	-10000	0	-0.42	3	3
GCN5L2	0.031	0.029	-10000	0	-0.42	1	1
SMAD3/SMAD4/TFE3	0.04	0.12	-10000	0	-0.3	39	39
MSG1/HSC70	0.032	0.062	-10000	0	-0.3	15	15
SMAD2	0.011	0.059	-10000	0	-0.14	16	16
SMAD3	0.01	0.091	-10000	0	-0.32	21	21
SMAD3/E2F4-5/DP1/p107/SMAD4	-0.001	0.079	-10000	0	-0.24	30	30
SMAD2/SMAD2/SMAD4	-0.001	0.063	0.26	4	-0.21	19	23
NCOR1	0.032	0.012	-10000	0	-10000	0	0
NCOA2	0.025	0.047	-10000	0	-0.42	5	5
NCOA1	0.031	0.045	-10000	0	-0.42	5	5
MYOD/E2A	0.032	0.077	-10000	0	-0.3	25	25
SMAD2-3/SMAD4/SP1/MIZ-1	0.035	0.18	-10000	0	-0.35	56	56
IFNB1	-0.005	0.096	0.36	1	-0.31	26	27
SMAD3/SMAD4/MEF2C	-0.003	0.17	-10000	0	-0.42	44	44
CITED1	0.029	0.031	-10000	0	-0.42	2	2
SMAD2-3/SMAD4/ARC105	0.021	0.12	-10000	0	-0.24	48	48
RBL1	0.033	0.022	-10000	0	-0.42	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.004	0.12	-10000	0	-0.42	31	31
RUNX1-3/PEBPB2	0.013	0.12	-10000	0	-0.26	70	70
SMAD7	-0.041	0.21	-10000	0	-0.52	56	56
MYC/MIZ-1	0.016	0.082	0.19	5	-0.29	29	34
SMAD3/SMAD4	0.04	0.13	0.32	36	-0.4	17	53
IL10	-0.034	0.12	-10000	0	-0.31	56	56
PIASy/HDAC complex	0.024	0.043	-10000	0	-0.42	3	3
PIAS3	0.036	0.011	-10000	0	-10000	0	0
CDK2	0.035	0.033	-10000	0	-0.42	2	2
IL5	-0.035	0.13	-10000	0	-0.28	93	93
CDK4	0.038	0.017	-10000	0	-10000	0	0
PIAS4	0.024	0.043	-10000	0	-0.42	3	3
ATF3	0.011	0.084	-10000	0	-0.42	18	18
SMAD3/SMAD4/SP1	0.014	0.17	-10000	0	-0.33	71	71
FOXG1	-0.001	0.003	-10000	0	-10000	0	0
FOXO3	0.006	0.03	-10000	0	-0.2	4	4
FOXO1	0.006	0.029	-10000	0	-0.23	3	3
FOXO4	0.006	0.029	-10000	0	-0.23	3	3
heart looping	-0.029	0.14	0.34	3	-0.38	45	48
CEBPB	0.025	0.053	-10000	0	-0.42	6	6
SMAD3/SMAD4/DLX1	0.033	0.11	-10000	0	-0.26	31	31
MYOD1	0.014	0.095	-10000	0	-0.42	23	23
SMAD3/SMAD4/HNF4	0.032	0.11	-10000	0	-0.27	32	32
SMAD3/SMAD4/GATA3	-0.011	0.17	-10000	0	-0.3	105	105
SnoN/SIN3/HDAC complex/NCoR1	0.028	0.05	-10000	0	-0.42	6	6
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.017	0.15	-10000	0	-0.27	83	83
SMAD3/SMAD4/SP1-3	0.029	0.18	-10000	0	-0.36	64	64
MED15	0	0	-10000	0	-10000	0	0
SP1	0.009	0.076	-10000	0	-0.19	38	38
SIN3B	0.035	0.005	-10000	0	-10000	0	0
SIN3A	0.035	0.007	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.032	0.15	-10000	0	-0.26	91	91
ITGB5	-0.045	0.18	-10000	0	-0.5	59	59
TGIF/SIN3/HDAC complex/CtBP	0.018	0.061	-10000	0	-0.29	9	9
SMAD3/SMAD4/AR	-0.023	0.18	-10000	0	-0.31	115	115
AR	-0.053	0.18	-10000	0	-0.42	99	99
negative regulation of cell growth	0.012	0.099	-10000	0	-0.33	22	22
SMAD3/SMAD4/MYOD	0.018	0.12	-10000	0	-0.26	56	56
E2F5	0.011	0.087	-10000	0	-0.42	19	19
E2F4	0.03	0.014	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.045	0.13	-10000	0	-0.22	70	70
SMAD2-3/SMAD4/FOXO1-3a-4	-0.004	0.1	-10000	0	-0.3	42	42
TFDP1	0.032	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.007	0.2	-10000	0	-0.43	69	69
SMAD3/SMAD4/RUNX2	0.031	0.11	-10000	0	-0.28	33	33
TGIF2	0.029	0.05	-10000	0	-0.42	6	6
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	0.036	0.003	-10000	0	-10000	0	0

×

Visual signal transduction: Rods

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
mol:K +	0.03	0.046	-10000	0	-0.42	5	5
GNAT1/GTP	0.024	0.025	-10000	0	-0.3	3	3
Metarhodopsin II/Arrestin	0.009	0.094	-10000	0	-0.25	57	57
PDE6G/GNAT1/GTP	0.042	0.028	-10000	0	-0.25	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.032	0.036	-10000	0	-0.42	3	3
GRK1	0	0	-10000	0	-10000	0	0
CNG Channel	-0.015	0.12	-10000	0	-0.22	123	123
mol:Na +	0.025	0.098	-10000	0	-0.25	45	45
mol:ADP	0	0	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.007	0.12	-10000	0	-0.27	73	73
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.037	0.11	-10000	0	-0.26	42	42
CNGB1	0.03	0.014	-10000	0	-10000	0	0
RDH5	0.033	0.011	-10000	0	-10000	0	0
SAG	-0.024	0.14	-10000	0	-0.42	58	58
mol:Ca2+	-0.034	0.087	0.33	6	-0.39	10	16
Na + (4 Units)	0.016	0.093	-10000	0	-0.26	31	31
RGS9	0.017	0.07	-10000	0	-0.42	12	12
GNB1/GNGT1	0.036	0.062	-10000	0	-0.3	16	16
GNAT1/GDP	0.018	0.11	-10000	0	-0.23	76	76
GUCY2D	0.032	0.012	-10000	0	-10000	0	0
GNGT1	0.017	0.067	-10000	0	-0.42	11	11
GUCY2F	0.027	0.064	-10000	0	-0.42	10	10
GNB5	0.025	0.067	-10000	0	-0.42	11	11
mol:GMP (4 units)	-0.02	0.1	-10000	0	-0.22	105	105
mol:11-cis-retinal	0.033	0.01	-10000	0	-10000	0	0
mol:cGMP	0.048	0.084	-10000	0	-0.26	29	29
GNB1	0.032	0.045	-10000	0	-0.42	5	5
Rhodopsin	0.051	0.011	-10000	0	-10000	0	0
SLC24A1	0.03	0.046	-10000	0	-0.42	5	5
CNGA1	0.004	0.1	-10000	0	-0.42	28	28
Metarhodopsin II	0.023	0.004	-10000	0	-10000	0	0
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.064	0.077	-10000	0	-0.25	23	23
RGS9BP	-0.023	0.15	-10000	0	-0.42	61	61
Metarhodopsin II/Transducin	0.015	0.047	-10000	0	-0.21	20	20
GCAP Family/Ca ++	0.051	0.068	-10000	0	-0.25	23	23
PDE6A/B	-0.027	0.15	-10000	0	-0.3	112	112
mol:Pi	0.006	0.12	-10000	0	-0.27	73	73
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.05	0.058	-10000	0	-0.23	19	19
PDE6B	-0.064	0.19	-10000	0	-0.42	111	111
PDE6A	0.033	0.029	-10000	0	-0.42	2	2
PDE6G	0.034	0.01	-10000	0	-10000	0	0
RHO	0.036	0.006	-10000	0	-10000	0	0
PDE6	-0.015	0.15	-10000	0	-0.24	140	140
GUCA1A	0.022	0.075	-10000	0	-0.42	14	14
GC2/GCAP Family	0.067	0.09	-10000	0	-0.28	29	29
GUCA1C	0.026	0.064	-10000	0	-0.42	10	10
GUCA1B	0.034	0.021	-10000	0	-0.42	1	1

×

BMP receptor 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.045	0.1	-9999	-0.24	49	49
SMAD6-7/SMURF1	0.067	0.025	-9999	-0.26	1	1
NOG	0.029	0.037	-9999	-0.42	3	3
SMAD9	-0.029	0.16	-9999	-0.45	55	55
SMAD4	0.029	0.054	-9999	-0.42	7	7
SMAD5	-0.026	0.12	-9999	-0.38	28	28
BMP7/USAG1	-0.063	0.16	-9999	-0.31	139	139
SMAD5/SKI	-0.014	0.13	-9999	-0.38	29	29
SMAD1	0.012	0.07	-9999	-0.32	6	6
BMP2	0.021	0.073	-9999	-0.42	13	13
SMAD1/SMAD1/SMAD4	0.033	0.077	-9999	-0.32	2	2
BMPR1A	0.031	0.045	-9999	-0.42	5	5
BMPR1B	-0.004	0.11	-9999	-0.42	30	30
BMPR1A-1B/BAMBI	-0.02	0.14	-9999	-0.26	120	120
AHSG	0.034	0.008	-9999	-10000	0	0
CER1	0.034	0.009	-9999	-10000	0	0
BMP2-4/CER1	0.016	0.12	-9999	-0.26	71	71
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.015	0.12	-9999	-0.36	30	30
BMP2-4 (homodimer)	-0.006	0.13	-9999	-0.31	74	74
RGMB	0.028	0.057	-9999	-0.42	8	8
BMP6/BMPR2/BMPR1A-1B	0.051	0.091	-9999	-0.24	41	41
RGMA	0.019	0.073	-9999	-0.42	13	13
SMURF1	0.036	0.006	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.03	0.12	-9999	-0.36	32	32
BMP2-4/USAG1	-0.075	0.18	-9999	-0.29	189	189
SMAD6/SMURF1/SMAD5	-0.013	0.13	-9999	-0.38	28	28
SOSTDC1	-0.11	0.2	-9999	-0.42	151	151
BMP7/BMPR2/BMPR1A-1B	0.041	0.095	-9999	-0.24	45	45
SKI	0.036	0.002	-9999	-10000	0	0
BMP6 (homodimer)	0.027	0.05	-9999	-0.42	6	6
HFE2	0.026	0.064	-9999	-0.42	10	10
ZFYVE16	0.034	0.022	-9999	-0.42	1	1
MAP3K7	0.033	0.011	-9999	-10000	0	0
BMP2-4/CHRD	0.014	0.12	-9999	-0.28	70	70
SMAD5/SMAD5/SMAD4	-0.017	0.13	-9999	-0.38	30	30
MAPK1	0.033	0.022	-9999	-0.42	1	1
TAK1/TAB family	0.012	0.13	-9999	-0.36	24	24
BMP7 (homodimer)	0.016	0.072	-9999	-0.42	13	13
NUP214	0.035	0.021	-9999	-0.42	1	1
BMP6/FETUA	0.044	0.041	-9999	-0.3	6	6
SMAD1/SKI	0.027	0.08	-9999	-0.32	7	7
SMAD6	0.035	0.008	-9999	-10000	0	0
CTDSP2	0.034	0.029	-9999	-0.42	2	2
BMP2-4/FETUA	0.017	0.12	-9999	-0.26	69	69
MAP3K7IP1	0.034	0.009	-9999	-10000	0	0
GREM1	-0.002	0.12	-9999	-0.42	40	40
BMPR2 (homodimer)	0.034	0.029	-9999	-0.42	2	2
GADD34/PP1CA	0.06	0.039	-9999	-0.26	4	4
BMPR1A-1B (homodimer)	0.02	0.087	-9999	-0.3	34	34
CHRDL1	0.03	0.037	-9999	-0.42	3	3
ENDOFIN/SMAD1	0.026	0.08	-9999	-0.31	7	7
SMAD6-7/SMURF1/SMAD1	0.055	0.086	-9999	-0.31	5	5
SMAD6/SMURF1	0.036	0.006	-9999	-10000	0	0
BAMBI	-0.054	0.17	-9999	-0.42	93	93
SMURF2	0.028	0.042	-9999	-0.42	4	4
BMP2-4/CHRDL1	0.014	0.12	-9999	-0.27	75	75
BMP2-4/GREM1	-0.009	0.15	-9999	-0.29	101	101
SMAD7	0.034	0.021	-9999	-0.42	1	1
SMAD8A/SMAD8A/SMAD4	-0.023	0.17	-9999	-0.44	59	59
SMAD1/SMAD6	0.026	0.08	-9999	-0.33	6	6
TAK1/SMAD6	0.048	0.017	-9999	-10000	0	0
BMP7	0.016	0.073	-9999	-0.42	13	13
BMP6	0.027	0.05	-9999	-0.42	6	6
MAP3K7IP2	0.032	0.03	-9999	-0.42	2	2
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.018	0.11	-9999	-0.33	35	35
PPM1A	0.034	0.021	-9999	-0.42	1	1
SMAD1/SMURF2	0.022	0.076	-9999	-0.33	5	5
SMAD7/SMURF1	0.05	0.02	-9999	-0.3	1	1
CTDSPL	0.029	0.054	-9999	-0.42	7	7
PPP1CA	0.031	0.03	-9999	-0.42	2	2
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0.034	0.029	-9999	-0.42	2	2
PPP1R15A	0.034	0.021	-9999	-0.42	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.034	0.14	-9999	-0.41	36	36
CHRD	0.029	0.046	-9999	-0.42	5	5
BMPR2	0.034	0.029	-9999	-0.42	2	2
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.03	0.12	-9999	-0.38	31	31
BMP4	-0.028	0.15	-9999	-0.42	65	65
FST	0.023	0.064	-9999	-0.42	10	10
BMP2-4/NOG	0.012	0.12	-9999	-0.26	72	72
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.052	0.097	-9999	-0.23	45	45

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.028	0.057	-10000	0	-0.42	8	8
alphaV beta3 Integrin	0.036	0.071	-10000	0	-0.31	19	19
PTK2	-0.025	0.14	-10000	0	-0.43	36	36
positive regulation of JNK cascade	-0.002	0.13	-10000	0	-0.32	40	40
CDC42/GDP	0.009	0.17	-10000	0	-0.43	42	42
Rac1/GDP	0.01	0.16	-10000	0	-0.41	43	43
RAP1B	0.033	0.03	-10000	0	-0.42	2	2
RAP1A	0.031	0.045	-10000	0	-0.42	5	5
CTNNB1	0.025	0.067	-10000	0	-0.42	11	11
CDC42/GTP	0	0.16	-10000	0	-0.4	40	40
nectin-3/I-afadin	0.022	0.098	-10000	0	-0.32	35	35
RAPGEF1	-0.016	0.16	-10000	0	-0.45	45	45
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.021	0.18	-10000	0	-0.51	46	46
PDGFB-D/PDGFRB	0.028	0.057	-10000	0	-0.42	8	8
TLN1	-0.015	0.074	0.19	4	-0.34	16	20
Rap1/GTP	-0.006	0.12	-10000	0	-0.33	44	44
IQGAP1	0.035	0.008	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.047	0.064	-10000	0	-0.23	22	22
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.022	0.098	-10000	0	-0.32	35	35
PVR	0.031	0.041	-10000	0	-0.42	4	4
Necl-5(dimer)	0.031	0.041	-10000	0	-0.42	4	4
mol:GDP	-0.012	0.19	-10000	0	-0.51	45	45
MLLT4	0.02	0.078	-10000	0	-0.42	15	15
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
PI3K	0.054	0.12	-10000	0	-0.28	47	47
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.033	0.064	-10000	0	-0.3	16	16
positive regulation of lamellipodium assembly	0.005	0.12	-10000	0	-0.32	41	41
PVRL1	0.03	0.024	-10000	0	-0.42	1	1
PVRL3	0.013	0.097	-10000	0	-0.42	24	24
PVRL2	0.026	0.064	-10000	0	-0.42	10	10
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
CDH1	-0.011	0.13	-10000	0	-0.42	45	45
CLDN1	-0.047	0.17	-10000	0	-0.42	86	86
JAM-A/CLDN1	0.002	0.14	-10000	0	-0.27	87	87
SRC	-0.035	0.2	-10000	0	-0.56	48	48
ITGB3	0.029	0.046	-10000	0	-0.42	5	5
nectin-1(dimer)/I-afadin/I-afadin	0.033	0.064	-10000	0	-0.3	16	16
FARP2	-0.017	0.2	-10000	0	-0.53	44	44
RAC1	0.035	0.006	-10000	0	-10000	0	0
CTNNA1	0.035	0.021	-10000	0	-0.42	1	1
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.038	0.097	-10000	0	-0.28	38	38
nectin-1/I-afadin	0.033	0.064	-10000	0	-0.3	16	16
nectin-2/I-afadin	0.032	0.076	-10000	0	-0.3	24	24
RAC1/GTP/IQGAP1/filamentous actin	0.046	0.013	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.035	0.093	-10000	0	-0.28	36	36
CDC42/GTP/IQGAP1/filamentous actin	0.045	0.014	-10000	0	-10000	0	0
F11R	0.026	0.038	-10000	0	-0.42	3	3
positive regulation of filopodium formation	-0.002	0.13	-10000	0	-0.32	40	40
alphaV/beta3 Integrin/Talin	0.008	0.11	0.27	1	-0.32	29	30
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.032	0.076	-10000	0	-0.3	24	24
nectin-2(dimer)/I-afadin/I-afadin	0.032	0.076	-10000	0	-0.3	24	24
PIP5K1C	-0.011	0.077	-10000	0	-0.24	39	39
VAV2	-0.006	0.19	-10000	0	-0.52	38	38
RAP1/GDP	0.01	0.16	-10000	0	-0.39	44	44
ITGAV	0.022	0.078	-10000	0	-0.42	15	15
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.035	0.1	-10000	0	-0.28	42	42
nectin-3(dimer)/I-afadin/I-afadin	0.022	0.098	-10000	0	-0.32	35	35
Rac1/GTP	0.008	0.15	-10000	0	-0.39	40	40
PTPRM	-0.006	0.089	-10000	0	-0.27	40	40
E-cadherin/beta catenin/alpha catenin	0.025	0.12	-10000	0	-0.22	78	78
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.035	0.008	-10000	0	-10000	0	0

×

mTOR signaling pathway

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
GBL	0.032	0.023	-10000	0	-0.42	1	1
MKNK1	0.035	0.006	-10000	0	-10000	0	0
mol:PIP3	-0.024	0.1	0.26	5	-0.26	65	70
FRAP1	-0.008	0.11	-10000	0	-0.43	25	25
AKT1	-0.025	0.096	0.2	9	-0.25	58	67
INSR	0.034	0.029	-10000	0	-0.42	2	2
Insulin Receptor/Insulin	0.045	0.026	-10000	0	-0.25	3	3
mol:GTP	0.011	0.097	0.29	2	-0.22	46	48
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.006	0.051	-10000	0	-0.19	16	16
TSC2	0.032	0.023	-10000	0	-0.42	1	1
RHEB/GDP	0.004	0.081	-10000	0	-0.2	50	50
TSC1	0.036	0.005	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.009	0.11	-10000	0	-0.3	65	65
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.011	0.068	-10000	0	-0.22	15	15
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0	0.092	0.24	4	-0.33	16	20
MAP3K5	-0.015	0.086	0.19	7	-0.25	51	58
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
apoptosis	-0.015	0.086	0.19	7	-0.25	51	58
mol:LY294002	0	0	0.001	2	-0.001	62	64
EIF4B	-0.002	0.085	0.28	2	-0.29	17	19
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.012	0.082	0.26	1	-0.27	16	17
eIF4E/eIF4G1/eIF4A1	0.002	0.075	-10000	0	-0.28	21	21
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.002	0.12	-10000	0	-0.27	75	75
mTOR/RHEB/GTP/Raptor/GBL	0.01	0.061	0.22	3	-0.21	11	14
FKBP1A	0.035	0.007	-10000	0	-10000	0	0
RHEB/GTP	0.02	0.091	0.27	2	-0.27	12	14
mol:Amino Acids	0	0	0.001	2	-0.001	62	64
FKBP12/Rapamycin	0.026	0.006	-10000	0	-10000	0	0
PDPK1	-0.033	0.094	0.17	23	-0.26	60	83
EIF4E	0.036	0.005	-10000	0	-10000	0	0
ASK1/PP5C	-0.035	0.22	-10000	0	-0.59	57	57
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.017	0.054	-10000	0	-0.38	1	1
TSC1/TSC2	0.013	0.1	0.32	2	-0.24	46	48
tumor necrosis factor receptor activity	0	0	0.001	62	-0.001	2	64
RPS6	0.034	0.022	-10000	0	-0.42	1	1
PPP5C	0.032	0.041	-10000	0	-0.42	4	4
EIF4G1	0.031	0.041	-10000	0	-0.42	4	4
IRS1	-0.031	0.11	-10000	0	-0.32	65	65
INS	0.034	0.021	-10000	0	-0.42	1	1
PTEN	0.027	0.06	-10000	0	-0.42	9	9
PDK2	-0.032	0.1	0.17	27	-0.26	64	91
EIF4EBP1	-0.068	0.32	-10000	0	-1.2	38	38
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
PPP2R5D	-0.007	0.1	-10000	0	-0.39	25	25
peptide biosynthetic process	0.017	0.03	0.19	5	-0.23	5	10
RHEB	0.035	0.007	-10000	0	-10000	0	0
EIF4A1	0.032	0.012	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.004	14	-0.003	4	18
EEF2	0.017	0.03	0.19	5	-0.23	5	10
eIF4E/4E-BP1	-0.048	0.3	-10000	0	-1.1	38	38

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.021	0.16	0.26	4	-0.42	44	48
IKBKB	0.017	0.092	0.33	2	-0.3	4	6
AKT1	0.024	0.11	0.25	35	-0.23	18	53
IKBKG	0.027	0.079	0.24	5	-0.28	6	11
CALM1	-0.01	0.13	0.25	5	-0.41	29	34
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
MAP3K1	-0.02	0.18	0.32	2	-0.48	42	44
MAP3K7	0.033	0.01	-10000	0	-10000	0	0
mol:Ca2+	-0.011	0.14	0.26	5	-0.42	31	36
DOK1	0.027	0.061	-10000	0	-0.42	9	9
AP-1	-0.018	0.1	0.21	2	-0.25	43	45
LYN	0.03	0.014	-10000	0	-10000	0	0
BLNK	0.013	0.099	-10000	0	-0.42	25	25
SHC1	0.028	0.025	-10000	0	-0.42	1	1
BCR complex	0.025	0.074	-10000	0	-0.3	23	23
CD22	-0.018	0.12	0.26	1	-0.44	30	31
CAMK2G	-0.009	0.12	0.24	7	-0.4	26	33
CSNK2A1	0.035	0.006	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.004	0.077	-10000	0	-0.24	36	36
GO:0007205	-0.011	0.14	0.26	5	-0.42	31	36
SYK	0.005	0.11	-10000	0	-0.42	34	34
ELK1	-0.012	0.13	0.25	5	-0.42	29	34
NFATC1	0.022	0.13	0.26	22	-0.36	29	51
B-cell antigen/BCR complex	0.025	0.074	-10000	0	-0.3	23	23
PAG1/CSK	0.035	0.051	-10000	0	-0.3	9	9
NFKBIB	0.027	0.05	0.15	8	-0.12	21	29
HRAS	0.003	0.12	0.25	13	-0.34	30	43
NFKBIA	0.028	0.05	0.15	8	-0.12	21	29
NF-kappa-B/RelA/I kappa B beta	0.032	0.045	0.15	9	-0.093	6	15
RasGAP/Csk	0.038	0.1	-10000	0	-0.26	35	35
mol:GDP	-0.01	0.14	0.26	5	-0.4	34	39
PTEN	0.027	0.061	-10000	0	-0.42	9	9
CD79B	0.007	0.094	-10000	0	-0.42	23	23
NF-kappa-B/RelA/I kappa B alpha	0.032	0.044	0.14	10	-0.092	4	14
GRB2	0.033	0.011	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.01	0.18	0.34	2	-0.5	40	42
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
mol:IP3	-0.012	0.14	0.27	4	-0.42	32	36
CSK	0.034	0.022	-10000	0	-0.42	1	1
FOS	-0.036	0.14	0.24	4	-0.39	42	46
CHUK	0.016	0.1	0.25	3	-0.33	18	21
IBTK	0.032	0.03	-10000	0	-0.42	2	2
CARD11/BCL10/MALT1/TAK1	0.01	0.13	0.27	1	-0.4	26	27
PTPN6	-0.01	0.12	0.25	1	-0.48	23	24
RELA	0.036	0.006	-10000	0	-10000	0	0
BCL2A1	0.023	0.035	0.14	3	-0.1	1	4
VAV2	0	0.14	0.26	2	-0.5	26	28
ubiquitin-dependent protein catabolic process	0.03	0.05	0.15	8	-0.12	21	29
BTK	-0.012	0.19	-10000	0	-1.1	15	15
CD19	-0.017	0.12	0.26	1	-0.47	26	27
MAP4K1	0.035	0.007	-10000	0	-10000	0	0
CD72	0.009	0.1	-10000	0	-0.42	27	27
PAG1	0.02	0.061	-10000	0	-0.42	9	9
MAPK14	-0.015	0.16	0.28	3	-0.41	42	45
SH3BP5	0.021	0.078	-10000	0	-0.42	15	15
PIK3AP1	-0.02	0.15	0.28	4	-0.45	36	40
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.02	0.16	-10000	0	-0.47	42	42
RAF1	0.003	0.12	0.24	12	-0.33	26	38
RasGAP/p62DOK/SHIP	0.026	0.099	-10000	0	-0.26	40	40
CD79A	0.031	0.023	-10000	0	-0.42	1	1
re-entry into mitotic cell cycle	-0.018	0.1	0.21	2	-0.25	43	45
RASA1	0.029	0.05	-10000	0	-0.42	6	6
MAPK3	0.012	0.1	0.24	20	-0.31	16	36
MAPK1	0.002	0.1	0.26	9	-0.31	19	28
CD72/SHP1	0.018	0.16	0.3	16	-0.47	29	45
NFKB1	0.036	0.005	-10000	0	-10000	0	0
MAPK8	-0.016	0.16	0.3	5	-0.41	41	46
actin cytoskeleton organization	0.019	0.14	0.3	13	-0.44	27	40
NF-kappa-B/RelA	0.065	0.087	0.28	8	-0.2	16	24
Calcineurin	0.004	0.13	0.25	1	-0.38	27	28
PI3K	-0.025	0.11	-10000	0	-0.39	28	28
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.011	0.15	0.3	4	-0.44	37	41
SOS1	0.035	0.021	-10000	0	-0.42	1	1
Bam32/HPK1	-0.065	0.31	-10000	0	-0.73	79	79
DAPP1	-0.1	0.34	-10000	0	-0.84	77	77
cytokine secretion	0.023	0.13	0.25	24	-0.34	28	52
mol:DAG	-0.012	0.14	0.27	4	-0.42	32	36
PLCG2	0.02	0.055	-10000	0	-0.42	7	7
MAP2K1	0.002	0.11	0.24	13	-0.33	21	34
B-cell antigen/BCR complex/FcgammaRIIB	0.02	0.094	-10000	0	-0.29	34	34
mol:PI-3-4-5-P3	0	0.11	0.25	20	-0.3	23	43
ETS1	-0.009	0.11	0.23	7	-0.37	26	33
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.033	0.12	-10000	0	-0.26	55	55
B-cell antigen/BCR complex/LYN	-0.013	0.12	0.27	1	-0.45	31	32
MALT1	0.031	0.041	-10000	0	-0.42	4	4
TRAF6	0.035	0.021	-10000	0	-0.42	1	1
RAC1	0.008	0.14	0.33	5	-0.46	27	32
B-cell antigen/BCR complex/LYN/SYK	-0.002	0.14	-10000	0	-0.48	27	27
CARD11	-0.013	0.14	0.26	7	-0.44	30	37
FCGR2B	0.001	0.11	-10000	0	-0.42	30	30
PPP3CA	0.027	0.061	-10000	0	-0.42	9	9
BCL10	0.034	0.008	-10000	0	-10000	0	0
IKK complex	0.024	0.05	0.16	18	-0.14	1	19
PTPRC	0.007	0.094	-10000	0	-0.42	23	23
PDPK1	0.005	0.085	0.21	28	-0.22	16	44
PPP3CB	0.035	0.021	-10000	0	-0.42	1	1
PPP3CC	0.024	0.043	-10000	0	-0.42	4	4
POU2F2	0.025	0.032	0.13	5	-0.1	1	6

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.007	0.034	-10000	0	-0.097	60	60
STMN1	0.005	0.051	-10000	0	-0.34	10	10
Aurora B/RasGAP/Survivin	0.028	0.1	-10000	0	-0.28	43	43
Chromosomal passenger complex/Cul3 protein complex	-0.044	0.12	-10000	0	-0.35	40	40
BIRC5	-0.004	0.12	-10000	0	-0.44	38	38
DES	-0.062	0.26	-10000	0	-0.68	72	72
Aurora C/Aurora B/INCENP	0.053	0.049	-10000	0	-0.24	10	10
Aurora B/TACC1	0.023	0.064	-10000	0	-0.25	23	23
Aurora B/PP2A	0.045	0.034	-10000	0	-0.31	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.009	0.022	-10000	0	-0.18	6	6
mitotic metaphase/anaphase transition	0.001	0.006	0.014	49	-0.01	1	50
NDC80	0.005	0.025	-10000	0	-0.31	3	3
Cul3 protein complex	0.015	0.12	-10000	0	-0.26	76	76
KIF2C	-0.056	0.21	-10000	0	-0.66	49	49
PEBP1	-0.001	0.004	0.01	2	-0.014	38	40
KIF20A	0.004	0.12	-10000	0	-0.42	35	35
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.04	0.051	-10000	0	-0.31	9	9
SEPT1	0.031	0.023	-10000	0	-0.42	1	1
SMC2	0	0	-10000	0	-10000	0	0
SMC4	0	0	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.044	0.18	-10000	0	-0.51	60	60
PSMA3	0.035	0.006	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.004	0.009	53	-0.009	7	60
H3F3B	0.014	0.028	-10000	0	-0.29	4	4
AURKB	0.03	0.04	-10000	0	-0.45	3	3
AURKC	0.034	0.021	-10000	0	-0.42	1	1
CDCA8	0.017	0.085	-10000	0	-0.44	16	16
cytokinesis	-0.045	0.23	-10000	0	-0.64	49	49
Aurora B/Septin1	-0.026	0.22	-10000	0	-0.62	44	44
AURKA	0	0.004	0.009	53	-0.009	7	60
INCENP	0.025	0.053	-10000	0	-0.44	6	6
KLHL13	-0.034	0.16	-10000	0	-0.42	73	73
BUB1	-0.012	0.14	-10000	0	-0.42	52	52
hSgo1/Aurora B/Survivin	0.025	0.12	-10000	0	-0.34	39	39
EVI5	0.031	0.041	-10000	0	-0.42	4	4
RhoA/GTP	-0.021	0.22	-10000	0	-0.58	49	49
SGOL1	0.02	0.08	-10000	0	-0.42	16	16
CENPA	-0.039	0.15	-10000	0	-0.31	82	82
NCAPG	0	0	-10000	0	-10000	0	0
Aurora B/HC8 Proteasome	0.045	0.034	-10000	0	-0.31	3	3
NCAPD2	0	0	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.044	0.043	-10000	0	-0.31	6	6
RHOA	0.026	0.061	-10000	0	-0.42	9	9
NCAPH	0	0	-10000	0	-10000	0	0
NPM1	-0.02	0.12	-10000	0	-0.32	57	57
RASA1	0.029	0.05	-10000	0	-0.42	6	6
KLHL9	0.032	0.03	-10000	0	-0.42	2	2
mitotic prometaphase	-0.001	0.004	0.01	2	-0.014	38	40
proteasomal ubiquitin-dependent protein catabolic process	0.045	0.034	-10000	0	-0.31	3	3
PPP1CC	0.033	0.035	-10000	0	-0.42	3	3
Centraspindlin	-0.03	0.23	-10000	0	-0.61	52	52
RhoA/GDP	0.02	0.043	-10000	0	-0.3	9	9
NSUN2	-0.017	0.11	-10000	0	-0.3	57	57
MYLK	0.006	0.059	-10000	0	-0.3	17	17
KIF23	0.006	0.11	-10000	0	-0.43	30	30
VIM	-0.006	0.072	-10000	0	-0.3	27	27
RACGAP1	0.02	0.085	-10000	0	-0.43	17	17
mitosis	0	0	-10000	0	-10000	0	0
NCL	-0.022	0.13	-10000	0	-0.35	51	51
Chromosomal passenger complex	-0.048	0.18	-10000	0	-0.46	59	59
Chromosomal passenger complex/EVI5	0.04	0.13	-10000	0	-0.33	48	48
TACC1	0.011	0.089	-10000	0	-0.42	20	20
PPP2R5D	0.035	0.006	-10000	0	-10000	0	0
CUL3	0.032	0.041	-10000	0	-0.42	4	4
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.026	0.004	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAP3K7IP2	0.032	0.03	-10000	0	-0.42	2	2
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.01	0.11	-10000	0	-0.37	29	29
IRAK/TOLLIP	0.041	0.017	0.18	5	-10000	0	5
IKBKB	0.03	0.014	-10000	0	-10000	0	0
IKBKG	0.036	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0.026	0.09	-10000	0	-0.3	35	35
IL1A	0.032	0.041	-10000	0	-0.42	4	4
IL1B	-0.023	0.11	-10000	0	-0.34	53	53
IRAK/TRAF6/p62/Atypical PKCs	0.059	0.05	-10000	0	-0.21	12	12
IL1R2	0.004	0.11	-10000	0	-0.42	31	31
IL1R1	-0.005	0.13	-10000	0	-0.42	43	43
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.022	0.12	-10000	0	-0.41	26	26
TOLLIP	0.035	0.007	-10000	0	-10000	0	0
TICAM2	0	0	-10000	0	-10000	0	0
MAP3K3	0.031	0.013	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.06	0.034	-10000	0	-0.26	2	2
IKK complex/ELKS	0.025	0.079	0.27	1	-0.32	9	10
JUN	-0.028	0.068	0.24	2	-0.45	2	4
MAP3K7	0.033	0.011	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.006	0.15	-10000	0	-0.28	94	94
IL1 alpha/IL1R1/IL1RAP/MYD88	0.052	0.098	-10000	0	-0.23	50	50
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.063	0.1	-10000	0	-0.22	53	53
IL1 beta fragment/IL1R1/IL1RAP	-0.011	0.14	-10000	0	-0.29	87	87
NFKB1	0.036	0.005	-10000	0	-10000	0	0
MAPK8	-0.014	0.059	0.28	3	-0.38	1	4
IRAK1	0.018	0.003	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.003	0.13	-10000	0	-0.32	73	73
IRAK4	0.033	0.035	-10000	0	-0.42	3	3
PRKCI	0.025	0.064	-10000	0	-0.42	10	10
TRAF6	0.035	0.021	-10000	0	-0.42	1	1
PI3K	0.036	0.065	-10000	0	-0.3	17	17
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.018	0.13	-10000	0	-0.39	36	36
CHUK	0.026	0.067	-10000	0	-0.42	11	11
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.011	0.14	-10000	0	-0.29	87	87
IL1 beta/IL1R2	-0.019	0.13	-10000	0	-0.3	85	85
IRAK/TRAF6/TAK1/TAB1/TAB2	0.075	0.045	-10000	0	-0.21	3	3
NF kappa B1 p50/RelA	-0.004	0.13	-10000	0	-0.26	91	91
IRAK3	0.027	0.046	-10000	0	-0.42	5	5
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.001	0.13	-10000	0	-0.27	88	88
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.009	0.084	-10000	0	-0.23	53	53
IL1 alpha/IL1R1/IL1RAP	0.038	0.095	-10000	0	-0.26	46	46
RELA	0.035	0.006	-10000	0	-10000	0	0
MAP3K7IP1	0.034	0.009	-10000	0	-10000	0	0
SQSTM1	0.034	0.021	-10000	0	-0.42	1	1
MYD88	0.031	0.041	-10000	0	-0.42	4	4
IRAK/TRAF6/MEKK3	0.053	0.03	-10000	0	-0.22	1	1
IL1RAP	0.033	0.022	-10000	0	-0.42	1	1
UBE2N	0.035	0.006	-10000	0	-10000	0	0
IRAK/TRAF6	-0.015	0.11	-10000	0	-0.25	73	73
CASP1	0.002	0.11	-10000	0	-0.42	30	30
IL1RN/IL1R2	0.003	0.12	-10000	0	-0.32	62	62
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.003	0.14	-10000	0	-0.28	88	88
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.003	0.11	-10000	0	-0.32	45	45
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
IL1RN	0.001	0.12	-10000	0	-0.42	37	37
TRAF6/TAK1/TAB1/TAB2	0.071	0.043	-10000	0	-0.21	3	3
MAP2K6	-0.01	0.057	0.27	2	-0.22	13	15

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.004	0.11	-10000	0	-0.44	29	29
PDGF/PDGFRA/CRKL	0.02	0.088	-10000	0	-0.3	32	32
positive regulation of JUN kinase activity	0.048	0.073	-10000	0	-0.23	22	22
CRKL	0.031	0.041	-10000	0	-0.42	4	4
PDGF/PDGFRA/Caveolin-3	0.022	0.086	-10000	0	-0.3	30	30
AP1	-0.14	0.3	-10000	0	-0.81	78	78
mol:IP3	-0.014	0.08	-10000	0	-0.32	27	27
PLCG1	-0.014	0.08	-10000	0	-0.32	27	27
PDGF/PDGFRA/alphaV Integrin	0.014	0.1	-10000	0	-0.32	42	42
RAPGEF1	0.036	0.004	-10000	0	-10000	0	0
CRK	0.032	0.023	-10000	0	-0.42	1	1
mol:Ca2+	-0.014	0.08	-10000	0	-0.32	27	27
CAV3	0.034	0.021	-10000	0	-0.42	1	1
CAV1	0.027	0.054	-10000	0	-0.42	7	7
SHC/Grb2/SOS1	0.05	0.074	-10000	0	-0.23	22	22
PDGF/PDGFRA/Shf	0.022	0.086	-10000	0	-0.3	30	30
FOS	-0.14	0.3	0.31	2	-0.8	78	80
JUN	-0.053	0.083	-10000	0	-0.34	36	36
oligodendrocyte development	0.014	0.1	-10000	0	-0.32	42	42
GRB2	0.033	0.011	-10000	0	-10000	0	0
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
mol:DAG	-0.014	0.08	-10000	0	-0.32	27	27
PDGF/PDGFRA	-0.004	0.11	-10000	0	-0.44	29	29
actin cytoskeleton reorganization	0.02	0.09	-10000	0	-0.3	33	33
SRF	0.018	0.012	-10000	0	-10000	0	0
SHC1	0.028	0.025	-10000	0	-0.42	1	1
PI3K	0.034	0.099	-10000	0	-0.28	40	40
PDGF/PDGFRA/Crk/C3G	0.044	0.079	-10000	0	-0.25	30	30
JAK1	-0.01	0.079	-10000	0	-0.31	30	30
ELK1/SRF	-0.026	0.071	0.15	20	-0.26	30	50
SHB	0.031	0.046	-10000	0	-0.42	5	5
SHF	0.033	0.022	-10000	0	-0.42	1	1
CSNK2A1	0.04	0.021	-10000	0	-10000	0	0
GO:0007205	-0.023	0.084	-10000	0	-0.35	28	28
SOS1	0.035	0.021	-10000	0	-0.42	1	1
Ras protein signal transduction	0.048	0.073	-10000	0	-0.23	22	22
PDGF/PDGFRA/SHB	0.02	0.09	-10000	0	-0.3	33	33
PDGF/PDGFRA/Caveolin-1	0.017	0.097	-10000	0	-0.33	33	33
ITGAV	0.022	0.078	-10000	0	-0.42	15	15
ELK1	-0.036	0.08	0.24	2	-0.32	30	32
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
PDGF/PDGFRA/Crk	0.019	0.085	-10000	0	-0.3	30	30
JAK-STAT cascade	-0.01	0.079	-10000	0	-0.31	30	30
cell proliferation	0.022	0.086	-10000	0	-0.3	30	30

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.045	0.086	-10000	0	-0.22	39	39
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.031	0.041	-10000	0	-0.42	4	4
STAT1 (dimer)/Cbp/p300	0.035	0.1	0.31	2	-0.31	19	21
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.052	0.051	-10000	0	-0.26	4	4
antigen processing and presentation of peptide antigen via MHC class I	-0.016	0.093	-10000	0	-0.25	48	48
CaM/Ca2+	0.047	0.085	-10000	0	-0.21	39	39
RAP1A	0.031	0.045	-10000	0	-0.42	5	5
STAT1 (dimer)/SHP2	0.017	0.095	0.28	3	-0.24	47	50
AKT1	-0.01	0.093	0.28	11	-0.29	9	20
MAP2K1	-0.022	0.081	0.27	3	-0.28	13	16
MAP3K11	0.005	0.079	0.26	5	-0.21	40	45
IFNGR1	0.03	0.022	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.005	0.13	-10000	0	-0.42	24	24
Rap1/GTP	0.001	0.067	-10000	0	-0.21	30	30
CRKL/C3G	0.047	0.034	-10000	0	-0.3	4	4
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.059	0.093	-10000	0	-0.22	39	39
CEBPB	-0.016	0.16	0.33	3	-0.51	30	33
STAT3	0.028	0.031	-10000	0	-0.42	2	2
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.054	0.13	-10000	0	-0.84	6	6
STAT1	-0.002	0.09	0.29	3	-0.24	47	50
CALM1	0.035	0.007	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.007	0.12	-10000	0	-0.42	38	38
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
STAT1 (dimer)/PIAS1	0.017	0.093	0.29	3	-0.23	46	49
CEBPB/PTGES2/Cbp/p300	0.005	0.11	-10000	0	-0.33	31	31
mol:Ca2+	0.042	0.083	-10000	0	-0.21	39	39
MAPK3	-0.015	0.14	0.4	1	-0.67	11	12
STAT1 (dimer)	-0.011	0.13	-10000	0	-0.34	48	48
MAPK1	-0.044	0.2	0.4	1	-0.7	35	36
JAK2	0.028	0.036	-10000	0	-0.42	2	2
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
JAK1	0.029	0.04	-10000	0	-0.41	3	3
CAMK2D	0.022	0.075	-10000	0	-0.42	14	14
DAPK1	-0.007	0.13	0.31	2	-0.48	21	23
SMAD7	-0.001	0.058	0.16	8	-0.16	20	28
CBL/CRKL/C3G	0.034	0.084	0.3	2	-0.21	33	35
PI3K	0.036	0.095	-10000	0	-0.22	48	48
IFNG	-0.007	0.12	-10000	0	-0.42	38	38
apoptosis	-0.061	0.18	0.31	1	-0.42	87	88
CAMK2G	0.036	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	0.028	0.031	-10000	0	-0.42	2	2
CAMK2A	0.035	0.021	-10000	0	-0.42	1	1
CAMK2B	-0.012	0.13	-10000	0	-0.42	47	47
FRAP1	-0.016	0.085	0.28	9	-0.28	7	16
PRKCD	-0.011	0.092	0.29	10	-0.3	8	18
RAP1B	0.033	0.03	-10000	0	-0.42	2	2
negative regulation of cell growth	-0.016	0.093	-10000	0	-0.25	48	48
PTPN2	0.035	0.008	-10000	0	-10000	0	0
EP300	0.032	0.03	-10000	0	-0.42	2	2
IRF1	-0.006	0.1	0.29	8	-0.42	15	23
STAT1 (dimer)/PIASy	0.013	0.094	0.29	3	-0.24	38	41
SOCS1	0.018	0.13	-10000	0	-1.1	6	6
mol:GDP	0.031	0.079	0.28	2	-0.2	34	36
CASP1	-0.012	0.083	0.16	8	-0.24	43	51
PTGES2	0.036	0.005	-10000	0	-10000	0	0
IRF9	0	0.049	0.12	4	-0.15	19	23
mol:PI-3-4-5-P3	0.021	0.086	-10000	0	-0.21	48	48
RAP1/GDP	0.025	0.08	-10000	0	-0.25	15	15
CBL	0.004	0.073	0.29	2	-0.21	37	39
MAP3K1	-0.005	0.089	0.26	5	-0.22	57	62
PIAS1	0.035	0.007	-10000	0	-10000	0	0
PIAS4	0.032	0.036	-10000	0	-0.42	3	3
antigen processing and presentation of peptide antigen via MHC class II	-0.016	0.093	-10000	0	-0.25	48	48
PTPN11	0.008	0.08	0.29	4	-0.21	39	43
CREBBP	0.033	0.011	-10000	0	-10000	0	0
RAPGEF1	0.036	0.004	-10000	0	-10000	0	0

×

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

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
BAG4	0.028	0.025	-10000	0	-0.42	1	1
Caspase 8 (4 units)	0.029	0.13	-10000	0	-0.4	23	23
NEF	-0.011	0.049	-10000	0	-0.17	45	45
NFKBIA	0.022	0.05	-10000	0	-0.46	2	2
BIRC3	-0.012	0.14	-10000	0	-0.46	40	40
CYCS	-0.005	0.12	0.19	4	-0.33	40	44
RIPK1	0.035	0.007	-10000	0	-10000	0	0
CD247	-0.011	0.049	-10000	0	-0.17	45	45
MAP2K7	0.004	0.18	-10000	0	-0.78	15	15
protein ubiquitination	-0.015	0.12	0.22	2	-0.37	23	25
CRADD	0.03	0.05	-10000	0	-0.42	6	6
DAXX	0.036	0.006	-10000	0	-10000	0	0
FAS	0.008	0.11	-10000	0	-0.42	29	29
BID	-0.006	0.12	-10000	0	-0.3	57	57
NF-kappa-B/RelA/I kappa B alpha	0.042	0.099	-10000	0	-0.26	39	39
TRADD	0.03	0.014	-10000	0	-10000	0	0
MAP3K5	0.012	0.095	-10000	0	-0.42	23	23
CFLAR	0.031	0.045	-10000	0	-0.42	5	5
FADD	0.029	0.014	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.042	0.1	-10000	0	-0.26	39	39
MAPK8	0.003	0.16	0.42	1	-0.69	15	16
APAF1	0.032	0.041	-10000	0	-0.42	4	4
TRAF1	0.035	0.021	-10000	0	-0.42	1	1
TRAF2	0.034	0.029	-10000	0	-0.42	2	2
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.002	0.13	-10000	0	-0.31	54	54
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.014	0.14	-10000	0	-0.41	30	30
CHUK	-0.019	0.13	-10000	0	-0.4	24	24
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.055	0.095	-10000	0	-0.24	35	35
TCRz/NEF	-0.017	0.083	-10000	0	-0.28	45	45
TNF	0.026	0.061	-10000	0	-0.42	9	9
FASLG	-0.022	0.14	-10000	0	-0.52	36	36
NFKB1	0.023	0.041	-10000	0	-0.1	36	36
TNFR1A/BAG4/TNF-alpha	0.048	0.047	-10000	0	-0.25	6	6
CASP6	0.022	0.16	-10000	0	-0.53	24	24
CASP7	-0.041	0.2	0.29	1	-0.47	68	69
RELA	0.023	0.042	-10000	0	-0.1	39	39
CASP2	0.035	0.008	-10000	0	-10000	0	0
CASP3	-0.04	0.19	-10000	0	-0.46	65	65
TNFRSF1A	0.033	0.022	-10000	0	-0.42	1	1
TNFR1A/BAG4	0.039	0.028	-10000	0	-0.3	1	1
CASP8	0.036	0.004	-10000	0	-10000	0	0
CASP9	0.034	0.022	-10000	0	-0.42	1	1
MAP3K14	-0.013	0.13	0.24	2	-0.43	23	25
APAF-1/Caspase 9	-0.014	0.14	-10000	0	-0.34	54	54
BCL2	-0.031	0.16	0.58	1	-0.53	22	23

×

Arf6 downstream 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
PLAUR	-0.029	0.23	-10000	0	-0.98	28	28
regulation of axonogenesis	-0.001	0.058	0.29	12	-10000	0	12
myoblast fusion	-0.006	0.11	0.4	31	-10000	0	31
mol:GTP	0.01	0.066	-10000	0	-0.23	32	32
regulation of calcium-dependent cell-cell adhesion	-0.047	0.082	0.24	33	-10000	0	33
ARF1/GTP	0.024	0.056	-10000	0	-0.19	24	24
mol:GM1	0	0.047	-10000	0	-0.18	27	27
mol:Choline	-0.001	0.057	-10000	0	-0.27	16	16
lamellipodium assembly	-0.007	0.12	-10000	0	-0.45	34	34
MAPK3	0.009	0.085	-10000	0	-0.33	29	29
ARF6/GTP/NME1/Tiam1	0.048	0.082	-10000	0	-0.24	33	33
ARF1	0.027	0.025	-10000	0	-0.42	1	1
ARF6/GDP	0.006	0.11	-10000	0	-0.4	31	31
ARF1/GDP	0.008	0.099	-10000	0	-0.36	29	29
ARF6	0.031	0.056	-10000	0	-0.41	3	3
RAB11A	0.034	0.021	-10000	0	-0.42	1	1
TIAM1	0.025	0.06	-10000	0	-0.42	8	8
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.009	0.086	-10000	0	-0.34	28	28
actin filament bundle formation	-0.016	0.11	0.37	34	-10000	0	34
KALRN	0.001	0.082	-10000	0	-0.31	31	31
RAB11FIP3/RAB11A	0.047	0.043	-10000	0	-0.3	7	7
RhoA/GDP	0.017	0.11	-10000	0	-0.37	34	34
NME1	0.031	0.02	-10000	0	-10000	0	0
Rac1/GDP	0.022	0.11	-10000	0	-0.37	33	33
substrate adhesion-dependent cell spreading	0.01	0.066	-10000	0	-0.23	32	32
cortical actin cytoskeleton organization	-0.007	0.13	-10000	0	-0.46	34	34
RAC1	0.035	0.006	-10000	0	-10000	0	0
liver development	0.01	0.066	-10000	0	-0.23	32	32
ARF6/GTP	0.01	0.066	-10000	0	-0.23	32	32
RhoA/GTP	0.025	0.071	-10000	0	-0.21	35	35
mol:GDP	-0.009	0.1	-10000	0	-0.39	33	33
ARF6/GTP/RAB11FIP3/RAB11A	0.048	0.067	-10000	0	-0.21	15	15
RHOA	0.026	0.061	-10000	0	-0.42	9	9
PLD1	0.007	0.068	-10000	0	-0.23	32	32
RAB11FIP3	0.031	0.049	-10000	0	-0.42	6	6
tube morphogenesis	-0.007	0.12	-10000	0	-0.45	34	34
ruffle organization	0.001	0.058	-10000	0	-0.29	12	12
regulation of epithelial cell migration	0.01	0.066	-10000	0	-0.23	32	32
PLD2	0.012	0.052	-10000	0	-0.2	22	22
PIP5K1A	0.001	0.058	-10000	0	-0.3	12	12
mol:Phosphatidic acid	-0.001	0.057	-10000	0	-0.27	16	16
Rac1/GTP	-0.007	0.13	-10000	0	-0.46	34	34

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.007	0.054	-10000	0	-0.3	15	15
MAP4K4	-0.024	0.11	0.22	3	-0.3	42	45
BAG4	0.028	0.025	-10000	0	-0.42	1	1
PKC zeta/ceramide	-0.008	0.048	0.12	5	-0.22	14	19
NFKBIA	0.033	0.03	-10000	0	-0.42	2	2
BIRC3	-0.008	0.12	-10000	0	-0.42	40	40
BAX	0.011	0.034	-10000	0	-0.37	2	2
RIPK1	0.035	0.007	-10000	0	-10000	0	0
AKT1	0.002	0.082	0.66	7	-0.39	2	9
BAD	-0.011	0.05	0.19	2	-0.23	13	15
SMPD1	0.007	0.065	0.18	3	-0.22	19	22
RB1	-0.015	0.057	0.19	1	-0.23	22	23
FADD/Caspase 8	0.011	0.12	0.22	54	-0.33	23	77
MAP2K4	-0.022	0.064	0.19	2	-0.22	35	37
NSMAF	0.027	0.042	-10000	0	-0.42	4	4
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.009	0.054	0.19	8	-0.22	12	20
EGF	-0.069	0.19	-10000	0	-0.42	110	110
mol:ceramide	-0.008	0.052	0.13	10	-0.23	14	24
MADD	0.036	0.005	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.005	0.075	-10000	0	-0.31	28	28
ASAH1	0.009	0.088	-10000	0	-0.42	20	20
negative regulation of cell cycle	-0.015	0.057	0.18	2	-0.22	22	24
cell proliferation	-0.011	0.092	0.22	2	-0.22	33	35
BID	-0.013	0.14	-10000	0	-0.65	15	15
MAP3K1	-0.02	0.066	0.17	2	-0.22	37	39
EIF2A	-0.014	0.064	0.21	8	-0.22	23	31
TRADD	0.03	0.014	-10000	0	-10000	0	0
CRADD	0.03	0.05	-10000	0	-0.42	6	6
MAPK3	-0.007	0.053	0.19	7	-0.23	10	17
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.011	0.061	0.19	7	-0.24	12	19
Cathepsin D/ceramide	0.006	0.06	0.15	1	-0.22	19	20
FADD	0.007	0.11	0.22	53	-0.3	26	79
KSR1	-0.009	0.051	0.18	4	-0.23	13	17
MAPK8	-0.012	0.06	0.15	1	-0.21	24	25
PRKRA	-0.009	0.051	0.15	7	-0.23	13	20
PDGFA	0.021	0.082	-10000	0	-0.42	17	17
TRAF2	0.034	0.029	-10000	0	-0.42	2	2
IGF1	-0.038	0.16	-10000	0	-0.42	78	78
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.008	0.052	0.13	10	-0.23	14	24
CTSD	0.029	0.046	-10000	0	-0.42	5	5
regulation of nitric oxide biosynthetic process	0.051	0.012	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.011	0.098	0.24	2	-0.23	33	35
PRKCD	0.033	0.03	-10000	0	-0.42	2	2
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.005	0.075	-10000	0	-0.31	28	28
RelA/NF kappa B1	0.051	0.012	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.024	0.072	-10000	0	-0.42	13	13
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.013	0.1	-10000	0	-0.36	26	26
TNFR1A/BAG4/TNF-alpha	0.048	0.047	-10000	0	-0.25	6	6
mol:Sphingosine-1-phosphate	0.007	0.054	-10000	0	-0.3	15	15
MAP2K1	-0.01	0.053	0.18	12	-0.23	9	21
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.035	0.006	-10000	0	-10000	0	0
CYCS	0.031	0.07	0.16	68	-0.2	5	73
TNFRSF1A	0.033	0.022	-10000	0	-0.42	1	1
NFKB1	0.036	0.005	-10000	0	-10000	0	0
TNFR1A/BAG4	0.039	0.028	-10000	0	-0.3	1	1
EIF2AK2	-0.017	0.06	0.17	5	-0.22	26	31
TNF-alpha/TNFR1A/FAN	0.051	0.05	-10000	0	-0.25	8	8
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.01	0.091	-10000	0	-0.34	20	20
MAP2K2	-0.011	0.054	0.18	10	-0.22	11	21
SMPD3	-0.026	0.12	0.19	1	-0.3	74	75
TNF	0.026	0.061	-10000	0	-0.42	9	9
PKC zeta/PAR4	0.018	0.051	-10000	0	-0.3	13	13
mol:PHOSPHOCHOLINE	0.037	0.095	0.21	103	-0.2	4	107
NF kappa B1/RelA/I kappa B alpha	0.069	0.057	-10000	0	-0.22	15	15
AIFM1	0.027	0.066	0.15	67	-0.17	8	75
BCL2	-0.057	0.18	-10000	0	-0.42	99	99

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	0.047	0.055	-10000	0	-0.23	16	16
RGS9BP	-0.023	0.15	-10000	0	-0.42	61	61
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0	0	-10000	0	-10000	0	0
mol:Na +	0.024	0.061	-10000	0	-0.26	19	19
mol:ADP	0.008	0.019	-10000	0	-0.3	2	2
GNAT2	0.019	0.085	-10000	0	-0.42	18	18
RGS9-1/Gbeta5/R9AP	0.007	0.12	-10000	0	-0.27	73	73
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.026	0.076	-10000	0	-0.27	30	30
GRK7	0.034	0.029	-10000	0	-0.42	2	2
CNGB3	0.022	0.051	-10000	0	-0.42	6	6
Cone Metarhodopsin II/X-Arrestin	0.027	0.001	-10000	0	-10000	0	0
mol:Ca2+	0.04	0.089	0.2	91	-0.24	20	111
Cone PDE6	0.02	0.13	-10000	0	-0.24	84	84
Cone Metarhodopsin II	0.022	0.016	-10000	0	-0.22	2	2
Na + (4 Units)	0.038	0.064	-10000	0	-0.24	20	20
GNAT2/GDP	0.011	0.12	-10000	0	-0.24	85	85
GNB5	0.025	0.067	-10000	0	-0.42	11	11
mol:GMP (4 units)	0.005	0.078	0.19	16	-0.25	34	50
Cone Transducin	0.051	0.059	-10000	0	-0.24	16	16
SLC24A2	0.032	0.036	-10000	0	-0.42	3	3
GNB3/GNGT2	0.048	0.023	-10000	0	-0.3	1	1
GNB3	0.034	0.009	-10000	0	-10000	0	0
GNAT2/GTP	0.015	0.06	-10000	0	-0.3	18	18
CNGA3	0.018	0.078	-10000	0	-0.42	15	15
ARR3	0.036	0.002	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.025	0.061	-10000	0	-0.26	19	19
mol:Pi	0.006	0.12	-10000	0	-0.27	73	73
Cone CNG Channel	0.034	0.099	-10000	0	-0.25	44	44
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.032	0.036	-10000	0	-0.42	3	3
RGS9	0.017	0.07	-10000	0	-0.42	12	12
PDE6C	0.03	0.05	-10000	0	-0.42	6	6
GNGT2	0.033	0.03	-10000	0	-0.42	2	2
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.021	0.075	-10000	0	-0.42	14	14

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	0.041	0.11	-10000	0	-0.46	18	18
HDAC1	0.04	0.028	-10000	0	-0.42	1	1
AES	0.037	0.009	-10000	0	-10000	0	0
FBXW11	0.033	0.029	-10000	0	-0.42	2	2
DTX1	0.033	0.035	-10000	0	-0.42	3	3
LRP6/FZD1	0.041	0.055	-10000	0	-0.3	12	12
TLE1	0.006	0.11	-10000	0	-0.42	33	33
AP1	-0.025	0.11	-10000	0	-0.27	75	75
NCSTN	0.028	0.025	-10000	0	-0.42	1	1
ADAM10	0.033	0.03	-10000	0	-0.42	2	2
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.037	0.15	-10000	0	-0.64	10	10
NICD/RBPSUH	0.005	0.097	-10000	0	-0.46	18	18
WIF1	0.03	0.014	-10000	0	-10000	0	0
NOTCH1	0.014	0.099	-10000	0	-0.48	18	18
PSENEN	0.035	0.006	-10000	0	-10000	0	0
KREMEN2	-0.09	0.19	-10000	0	-0.42	129	129
DKK1	-0.027	0.14	-10000	0	-0.42	60	60
beta catenin/beta TrCP1	0.012	0.1	0.26	2	-0.35	16	18
APH1B	0.025	0.067	-10000	0	-0.42	11	11
APH1A	0.031	0.036	-10000	0	-0.42	3	3
AXIN1	0.015	0.053	0.26	1	-0.39	2	3
CtBP/CBP/TCF1/TLE1/AES	0.027	0.089	0.29	3	-0.24	28	31
PSEN1	0.032	0.041	-10000	0	-0.42	4	4
FOS	-0.031	0.15	-10000	0	-0.42	66	66
JUN	-0.001	0.12	-10000	0	-0.42	39	39
MAP3K7	0.036	0.014	-10000	0	-10000	0	0
CTNNB1	-0.004	0.097	0.23	5	-0.37	15	20
MAPK3	0.032	0.023	-10000	0	-0.42	1	1
DKK2/LRP6/Kremen 2	-0.044	0.15	-10000	0	-0.26	154	154
HNF1A	0.002	0.006	-10000	0	-10000	0	0
CTBP1	0.036	0.01	-10000	0	-10000	0	0
MYC	-0.083	0.35	-10000	0	-1.3	35	35
NKD1	0.028	0.038	-10000	0	-0.42	3	3
FZD1	0.028	0.057	-10000	0	-0.42	8	8
NOTCH1 precursor/Deltex homolog 1	0.042	0.11	-10000	0	-0.47	18	18
apoptosis	-0.025	0.11	-10000	0	-0.26	75	75
Delta 1/NOTCHprecursor	0.04	0.11	-10000	0	-0.46	18	18
DLL1	0.034	0.01	-10000	0	-10000	0	0
PPARD	0.006	0.11	-10000	0	-0.9	6	6
Gamma Secretase	0.069	0.068	-10000	0	-0.22	13	13
APC	-0.001	0.1	0.26	1	-0.44	20	21
DVL1	0.025	0.028	-10000	0	-0.26	2	2
CSNK2A1	0.035	0.007	-10000	0	-10000	0	0
MAP3K7IP1	0.037	0.012	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.061	0.16	-10000	0	-0.27	169	169
LRP6	0.029	0.046	-10000	0	-0.42	5	5
CSNK1A1	0.035	0.006	-10000	0	-10000	0	0
NLK	0.029	0.025	-10000	0	-0.24	1	1
CCND1	-0.2	0.5	-10000	0	-1.3	84	84
WNT1	0.035	0.021	-10000	0	-0.42	1	1
Axin1/APC/beta catenin	0.021	0.1	0.34	2	-0.45	9	11
DKK2	0.006	0.11	-10000	0	-0.42	31	31
NOTCH1 precursor/DVL1	0.037	0.1	-10000	0	-0.51	11	11
GSK3B	0.036	0.005	-10000	0	-10000	0	0
FRAT1	0.03	0.054	-10000	0	-0.42	7	7
NOTCH/Deltex homolog 1	0.043	0.11	-10000	0	-0.47	18	18
PPP2R5D	0.012	0.068	0.23	3	-0.32	17	20
MAPK1	0.033	0.022	-10000	0	-0.42	1	1
WNT1/LRP6/FZD1	0.071	0.058	-10000	0	-0.23	13	13
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.026	0.02	-10000	0	-10000	0	0

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	0.019	0.11	-10000	0	-0.27	53	53
fibroblast growth factor receptor signaling pathway	0.018	0.1	-10000	0	-0.27	53	53
LAMA1	0.034	0.009	-10000	0	-10000	0	0
PRNP	0.028	0.057	-10000	0	-0.42	8	8
GPC1/SLIT2	0.013	0.11	-10000	0	-0.31	52	52
SMAD2	0.005	0.064	0.19	6	-0.24	29	35
GPC1/PrPc/Cu2+	0.03	0.069	-10000	0	-0.26	26	26
GPC1/Laminin alpha1	0.036	0.068	-10000	0	-0.3	19	19
TDGF1	0.034	0.008	-10000	0	-10000	0	0
CRIPTO/GPC1	0.037	0.068	-10000	0	-0.3	19	19
APP/GPC1	0.016	0.1	-10000	0	-0.3	47	47
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.005	0.06	-10000	0	-0.26	25	25
FLT1	0.026	0.058	-10000	0	-0.42	8	8
GPC1/TGFB/TGFBR1/TGFBR2	0.049	0.081	-10000	0	-0.26	30	30
SERPINC1	0.028	0.025	-10000	0	-0.42	1	1
FYN	0.005	0.057	-10000	0	-0.26	23	23
FGR	0.009	0.053	-10000	0	-0.26	19	19
positive regulation of MAPKKK cascade	-0.025	0.12	-10000	0	-0.35	38	38
SLIT2	0.003	0.12	-10000	0	-0.42	35	35
GPC1/NRG	0.028	0.068	-10000	0	-0.3	19	19
NRG1	0.028	0.015	-10000	0	-10000	0	0
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.027	0.07	-10000	0	-0.26	26	26
LYN	0.009	0.045	-10000	0	-0.25	14	14
mol:Spermine	-0.003	0.058	-10000	0	-0.3	19	19
cell growth	0.018	0.1	-10000	0	-0.27	53	53
BMP signaling pathway	-0.018	0.087	0.42	19	-10000	0	19
SRC	0.008	0.055	-10000	0	-0.27	19	19
TGFBR1	0.027	0.061	-10000	0	-0.42	9	9
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	0.013	0.08	-10000	0	-0.42	16	16
GPC1	0.018	0.087	-10000	0	-0.42	19	19
TGFBR1 (dimer)	0.027	0.06	-10000	0	-0.42	9	9
VEGFA	0	0	-10000	0	-10000	0	0
BLK	0.006	0.046	-10000	0	-0.25	15	15
HCK	0.001	0.068	-10000	0	-0.26	33	33
FGF2	-0.001	0.11	-10000	0	-0.42	34	34
FGFR1	0.02	0.064	-10000	0	-0.42	10	10
VEGFR1 homodimer	0.026	0.057	-10000	0	-0.42	8	8
TGFBR2	0.033	0.036	-10000	0	-0.42	3	3
cell death	0.016	0.1	-10000	0	-0.3	47	47
ATIII/GPC1	0.03	0.065	-10000	0	-0.3	17	17
PLA2G2A/GPC1	0.022	0.09	-10000	0	-0.3	34	34
LCK	-0.019	0.095	-10000	0	-0.26	68	68
neuron differentiation	0.028	0.068	-10000	0	-0.3	19	19
PrPc/Cu2+	0.021	0.04	-10000	0	-0.3	8	8
APP	0.008	0.11	-10000	0	-0.42	29	29
TGFBR2 (dimer)	0.033	0.036	-10000	0	-0.42	3	3

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.001	0.047	0.2	23	-0.12	5	28
BUB1B	-0.019	0.097	0.12	1	-0.3	43	44
PLK1	0.003	0.033	0.091	10	-0.09	19	29
PLK1S1	0.002	0.019	0.054	10	-0.049	17	27
KIF2A	0.003	0.03	0.08	10	-0.081	19	29
regulation of mitotic centrosome separation	0.003	0.033	0.09	10	-0.089	19	29
GOLGA2	0.036	0.005	-10000	0	-10000	0	0
Hec1/SPC24	-0.008	0.019	-10000	0	-0.071	25	25
WEE1	-0.006	0.094	-10000	0	-0.35	27	27
cytokinesis	-0.022	0.14	-10000	0	-0.45	39	39
PP2A-alpha B56	-0.036	0.28	-10000	0	-0.7	72	72
AURKA	0.002	0.02	0.06	11	-0.055	5	16
PICH/PLK1	-0.018	0.095	-10000	0	-0.33	35	35
CENPE	-0.012	0.068	0.2	3	-0.25	31	34
RhoA/GTP	0.02	0.043	-10000	0	-0.3	9	9
positive regulation of microtubule depolymerization	0.003	0.03	0.08	10	-0.08	19	29
PPP2CA	0.031	0.045	-10000	0	-0.42	5	5
FZR1	0.035	0.006	-10000	0	-10000	0	0
TPX2	-0.008	0.078	-10000	0	-0.27	39	39
PAK1	0.014	0.086	-10000	0	-0.43	18	18
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	0.033	0.029	-10000	0	-0.42	2	2
CLSPN	0.004	0.057	-10000	0	-0.28	18	18
GORASP1	0.034	0.022	-10000	0	-0.42	1	1
metaphase	0.002	0.006	0.019	46	-10000	0	46
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.002	0.019	0.054	10	-0.049	17	27
G2 phase of mitotic cell cycle	-0.001	0.002	0.011	2	-10000	0	2
STAG2	0.036	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.007	0.11	-10000	0	-0.51	20	20
spindle elongation	0.003	0.033	0.09	10	-0.089	19	29
ODF2	0.036	0.005	-10000	0	-10000	0	0
BUB1	-0.074	0.29	-10000	0	-0.75	74	74
TPT1	-0.009	0.063	-10000	0	-0.19	52	52
CDC25C	-0.014	0.11	-10000	0	-0.36	42	42
CDC25B	0.028	0.045	-10000	0	-0.44	4	4
SGOL1	0.001	0.047	0.12	5	-0.2	23	28
RHOA	0.026	0.061	-10000	0	-0.42	9	9
CCNB1/CDK1	0.028	0.13	-10000	0	-0.37	41	41
CDC14B	0.005	0.024	-10000	0	-0.3	3	3
CDC20	0.017	0.087	-10000	0	-0.42	19	19
PLK1/PBIP1	-0.005	0.056	0.096	1	-0.21	28	29
mitosis	0	0.003	0.013	10	-10000	0	10
FBXO5	-0.003	0.05	0.13	9	-0.2	10	19
CDC2	0.014	0.097	-10000	0	-0.44	22	22
NDC80	0	0	-10000	0	-10000	0	0
metaphase plate congression	0.004	0.054	-10000	0	-0.25	20	20
ERCC6L	-0.013	0.11	-10000	0	-0.35	41	41
NLP/gamma Tubulin	0.007	0.028	0.072	15	-0.083	10	25
microtubule cytoskeleton organization	-0.009	0.063	-10000	0	-0.19	52	52
G2/M transition DNA damage checkpoint	0	0.003	0.011	19	-10000	0	19
PPP1R12A	0.036	0.005	-10000	0	-10000	0	0
interphase	0	0.003	0.011	19	-10000	0	19
PLK1/PRC1-2	0.014	0.11	-10000	0	-0.33	42	42
GRASP65/GM130/RAB1/GTP/PLK1	0.05	0.048	-10000	0	-0.19	2	2
RAB1A	0.035	0.021	-10000	0	-0.42	1	1
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.003	0.025	0.069	13	-0.069	13	26
mitotic prometaphase	-0.001	0.004	0.018	20	-10000	0	20
proteasomal ubiquitin-dependent protein catabolic process	0.015	0.054	-10000	0	-0.39	3	3
microtubule-based process	0.006	0.078	-10000	0	-0.25	36	36
Golgi organization	0.003	0.033	0.09	10	-0.089	19	29
Cohesin/SA2	0.021	0.035	-10000	0	-0.11	1	1
PPP1CB/MYPT1	0.052	0.009	-10000	0	-10000	0	0
KIF20A	0.003	0.12	-10000	0	-0.42	35	35
APC/C/CDC20	0.013	0.064	0.12	2	-0.25	20	22
PPP2R1A	0.035	0.007	-10000	0	-10000	0	0
chromosome segregation	-0.005	0.055	0.095	1	-0.21	28	29
PRC1	0.009	0.1	-10000	0	-0.42	27	27
ECT2	0.004	0.072	0.23	25	-0.23	16	41
C13orf34	0.003	0.028	0.074	13	-0.078	15	28
NUDC	0.004	0.054	-10000	0	-0.25	20	20
regulation of attachment of spindle microtubules to kinetochore	-0.018	0.096	0.12	1	-0.3	43	44
spindle assembly	0.01	0.035	0.088	22	-0.082	12	34
spindle stabilization	0.002	0.019	0.054	10	-0.049	17	27
APC/C/HCDH1	0.03	0.023	-10000	0	-0.25	3	3
MKLP2/PLK1	0.006	0.078	-10000	0	-0.25	36	36
CCNB1	0.011	0.1	-10000	0	-0.44	25	25
PPP1CB	0.036	0.005	-10000	0	-10000	0	0
BTRC	0.034	0.022	-10000	0	-0.42	1	1
ROCK2	0.007	0.059	-10000	0	-0.32	9	9
TUBG1	0.009	0.04	-10000	0	-0.18	16	16
G2/M transition of mitotic cell cycle	-0.022	0.11	-10000	0	-0.37	40	40
MLF1IP	-0.009	0.069	-10000	0	-0.3	27	27
INCENP	0.028	0.051	-10000	0	-0.43	6	6

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.02	0.071	-10000	0	-0.29	24	24
PDGFRB	0.029	0.058	-10000	0	-0.43	8	8
SPHK1	-0.034	0.2	-10000	0	-0.76	35	35
mol:S1P	-0.019	0.19	-10000	0	-0.65	35	35
S1P1/S1P/Gi	-0.018	0.16	-10000	0	-0.49	34	34
GNAO1	0.031	0.015	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/PLCgamma1	0	0.14	0.33	1	-0.45	27	28
PLCG1	-0.016	0.14	0.3	1	-0.45	31	32
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.029	0.058	-10000	0	-0.43	8	8
GNAI2	0.029	0.055	-10000	0	-0.42	7	7
GNAI3	0.036	0.008	-10000	0	-10000	0	0
GNAI1	0.018	0.088	-10000	0	-0.42	19	19
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	0.001	0.12	-10000	0	-0.52	23	23
S1P1/S1P	-0.01	0.17	0.25	1	-0.47	49	50
negative regulation of cAMP metabolic process	-0.017	0.15	-10000	0	-0.47	34	34
MAPK3	-0.011	0.16	0.31	8	-0.54	26	34
calcium-dependent phospholipase C activity	0	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.026	0.004	-10000	0	-10000	0	0
RhoA/GDP	0.02	0.043	-10000	0	-0.3	9	9
KDR	0.029	0.058	-10000	0	-0.22	21	21
PLCB2	-0.009	0.15	0.24	1	-0.42	47	48
RAC1	0.035	0.006	-10000	0	-10000	0	0
RhoA/GTP	-0.017	0.14	-10000	0	-0.4	49	49
receptor internalization	-0.009	0.16	0.24	1	-0.43	50	51
PTGS2	-0.011	0.16	-10000	0	-0.74	15	15
Rac1/GTP	-0.013	0.14	-10000	0	-0.38	52	52
RHOA	0.026	0.061	-10000	0	-0.42	9	9
VEGFA	-0.003	0.033	-10000	0	-0.15	24	24
negative regulation of T cell proliferation	-0.017	0.15	-10000	0	-0.47	34	34
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.024	0.07	-10000	0	-0.42	12	12
MAPK1	-0.019	0.15	-10000	0	-0.54	27	27
S1P1/S1P/PDGFB-D/PDGFRB	0.009	0.18	0.3	1	-0.45	48	49
ABCC1	0.03	0.042	-10000	0	-0.42	4	4

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.012	0.11	-10000	0	-0.22	76	76
TC10/GTP	0.029	0.068	-10000	0	-0.21	34	34
Insulin Receptor/Insulin/IRS1/Shp2	0.054	0.11	-10000	0	-0.25	55	55
HRAS	0.032	0.036	-10000	0	-0.42	3	3
APS homodimer	0	0	-10000	0	-10000	0	0
GRB14	-0.063	0.18	-10000	0	-0.42	98	98
FOXO3	-0.014	0.022	-10000	0	-0.096	2	2
AKT1	-0.045	0.13	0.33	6	-0.36	17	23
INSR	0.037	0.031	-10000	0	-0.42	2	2
Insulin Receptor/Insulin	0.081	0.06	-10000	0	-0.3	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.023	0.075	-10000	0	-0.42	14	14
SORBS1	0.007	0.11	-10000	0	-0.42	29	29
CRK	0.032	0.023	-10000	0	-0.42	1	1
PTPN1	0.005	0.038	-10000	0	-0.3	5	5
CAV1	-0.008	0.083	0.18	4	-0.23	58	62
CBL/APS/CAP/Crk-II/C3G	0.052	0.075	-10000	0	-0.22	30	30
Insulin Receptor/Insulin/IRS1/NCK2	0.054	0.11	-10000	0	-0.25	53	53
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.028	0.1	-10000	0	-0.22	66	66
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.019	0.08	-10000	0	-0.42	6	6
RPS6KB1	-0.04	0.11	0.32	5	-0.34	16	21
PARD6A	0.021	0.061	-10000	0	-0.42	9	9
CBL	0.032	0.012	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.007	0.11	-10000	0	-0.67	12	12
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.004	0.12	0.28	3	-0.28	31	34
HRAS/GTP	-0.001	0.063	-10000	0	-0.2	40	40
Insulin Receptor	0.037	0.031	-10000	0	-0.42	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.049	0.1	-10000	0	-0.23	42	42
PRKCI	0.004	0.11	-10000	0	-0.47	23	23
Insulin Receptor/Insulin/GRB14/PDK1	-0.036	0.12	-10000	0	-0.23	135	135
SHC1	0.028	0.025	-10000	0	-0.42	1	1
negative regulation of MAPKKK cascade	0.046	0.11	-10000	0	-0.58	13	13
PI3K	0.04	0.11	-10000	0	-0.23	66	66
NCK2	0.036	0.005	-10000	0	-10000	0	0
RHOQ	0.031	0.045	-10000	0	-0.42	5	5
mol:H2O2	0	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.024	0.025	-10000	0	-0.3	3	3
AKT2	-0.046	0.13	0.33	6	-0.36	17	23
PRKCZ	-0.008	0.084	-10000	0	-0.42	17	17
SH2B2	0	0	-10000	0	-10000	0	0
SHC/SHIP	-0.001	0.069	0.17	2	-0.21	44	46
F2RL2	-0.02	0.14	-10000	0	-0.42	58	58
TRIP10	0.032	0.041	-10000	0	-0.42	4	4
Insulin Receptor/Insulin/Shc	0.054	0.041	-10000	0	-0.22	3	3
TC10/GTP/CIP4/Exocyst	0.042	0.041	-10000	0	-0.25	9	9
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.075	0.06	-10000	0	-0.22	4	4
RAPGEF1	0.036	0.004	-10000	0	-10000	0	0
RASA1	0.029	0.05	-10000	0	-0.42	6	6
NCK1	0.034	0.021	-10000	0	-0.42	1	1
CBL/APS/CAP/Crk-II	0.039	0.072	-10000	0	-0.23	30	30
TC10/GDP	0.023	0.032	-10000	0	-0.3	5	5
Insulin Receptor/Insulin/SHC/GRB10	0.063	0.066	-10000	0	-0.23	13	13
INPP5D	-0.03	0.07	-10000	0	-0.22	55	55
SOS1	0.035	0.021	-10000	0	-0.42	1	1
SGK1	-0.008	0.01	-10000	0	-10000	0	0
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.036	0.004	-10000	0	-10000	0	0
IRS1	-0.014	0.14	-10000	0	-0.42	54	54
p62DOK/RasGAP	0.046	0.11	-10000	0	-0.58	13	13
INS	0.037	0.024	-10000	0	-0.42	1	1
mol:PI-3-4-P2	-0.03	0.069	-10000	0	-0.22	55	55
GRB2	0.033	0.011	-10000	0	-10000	0	0
EIF4EBP1	-0.049	0.1	0.3	2	-0.34	17	19
PTPRA	0.038	0.013	-10000	0	-10000	0	0
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
TC10/GTP/CIP4	0.042	0.041	-10000	0	-0.25	9	9
PDPK1	0.032	0.023	-10000	0	-0.42	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.006	0.077	-10000	0	-0.22	39	39
Insulin Receptor/Insulin/IRS1	0.035	0.1	-10000	0	-0.24	55	55
Insulin Receptor/Insulin/IRS3	0.054	0.034	-10000	0	-0.3	3	3
Par3/Par6	0.023	0.11	-10000	0	-0.23	69	69

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.031	0.24	-10000	0	-0.76	23	23
PCK1	0.019	0.17	-10000	0	-0.99	5	5
HNF4A	-0.01	0.25	0.56	3	-0.78	20	23
KCNJ11	-0.053	0.34	-10000	0	-0.98	44	44
AKT1	-0.001	0.17	-10000	0	-0.41	22	22
response to starvation	0.004	0.002	-10000	0	-10000	0	0
DLK1	-0.023	0.27	0.63	1	-0.81	21	22
NKX2-1	0.038	0.13	0.36	4	-0.36	5	9
ACADM	-0.032	0.26	-10000	0	-0.78	27	27
TAT	-0.004	0.15	-10000	0	-0.64	2	2
CEBPB	0.031	0.051	-10000	0	-0.42	6	6
CEBPA	0.03	0.07	-10000	0	-0.42	12	12
TTR	-0.03	0.28	0.57	1	-0.72	42	43
PKLR	0.013	0.25	-10000	0	-0.72	21	21
APOA1	-0.028	0.28	-10000	0	-0.88	22	22
CPT1C	-0.031	0.27	-10000	0	-0.82	29	29
ALAS1	0.011	0.18	-10000	0	-1.1	4	4
TFRC	-0.042	0.36	-10000	0	-1.2	37	37
FOXF1	0.027	0.025	-10000	0	-0.42	1	1
NF1	0.037	0.035	-10000	0	-0.37	3	3
HNF1A (dimer)	0.008	0.02	-10000	0	-0.21	4	4
CPT1A	-0.023	0.27	0.56	1	-0.86	24	25
HMGCS1	-0.021	0.24	-10000	0	-0.74	23	23
NR3C1	0.034	0.074	-10000	0	-0.4	14	14
CPT1B	-0.024	0.24	-10000	0	-0.75	22	22
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.035	0.021	-10000	0	-0.42	1	1
GCK	-0.025	0.25	-10000	0	-0.76	24	24
CREB1	0.042	0.029	-10000	0	-0.24	4	4
IGFBP1	0.01	0.14	-10000	0	-1.3	1	1
PDX1	0.006	0.15	-10000	0	-0.37	23	23
UCP2	-0.052	0.31	-10000	0	-0.86	45	45
ALDOB	-0.024	0.26	-10000	0	-0.8	22	22
AFP	-0.024	0.12	-10000	0	-0.82	3	3
BDH1	-0.034	0.26	-10000	0	-0.77	31	31
HADH	-0.024	0.26	-10000	0	-0.78	24	24
F2	-0.01	0.28	-10000	0	-0.87	20	20
HNF1A	0.008	0.02	-10000	0	-0.21	4	4
G6PC	0.04	0.091	-10000	0	-1.3	1	1
SLC2A2	0.003	0.2	-10000	0	-1.2	4	4
INS	0.024	0.024	0.2	2	-0.43	1	3
FOXA1	-0.037	0.18	-10000	0	-0.4	97	97
FOXA3	0.043	0.077	-10000	0	-0.23	24	24
FOXA2	-0.011	0.32	-10000	0	-0.88	24	24
ABCC8	-0.2	0.48	-10000	0	-0.9	151	151
ALB	-0.03	0.15	-10000	0	-0.81	9	9

×

TRAIL signaling pathway

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
TNFSF10	-0.007	0.13	-10000	0	-0.42	45	45
positive regulation of NF-kappaB transcription factor activity	0.01	0.097	-10000	0	-0.29	45	45
MAP2K4	-0.009	0.1	-10000	0	-0.36	25	25
IKBKB	0.03	0.014	-10000	0	-10000	0	0
TNFRSF10B	0.027	0.016	-10000	0	-10000	0	0
TNFRSF10A	0.023	0.047	-10000	0	-0.42	5	5
SMPD1	-0.006	0.071	-10000	0	-0.21	44	44
IKBKG	0.036	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.028	0.016	-10000	0	-10000	0	0
TRAIL/TRAILR2	0.009	0.099	-10000	0	-0.3	45	45
TRAIL/TRAILR3	0.008	0.097	-10000	0	-0.29	46	46
TRAIL/TRAILR1	0.007	0.1	-10000	0	-0.31	47	47
TRAIL/TRAILR4	0.01	0.097	-10000	0	-0.29	45	45
TRAIL/TRAILR1/DAP3/GTP	0.02	0.08	-10000	0	-0.24	36	36
IKK complex	0.013	0.092	-10000	0	-0.4	14	14
RIPK1	0.035	0.007	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.021	0.018	-10000	0	-0.3	1	1
MAPK3	-0.01	0.085	-10000	0	-0.3	40	40
MAP3K1	-0.006	0.11	-10000	0	-0.39	24	24
TRAILR4 (trimer)	0.027	0.016	-10000	0	-10000	0	0
TRADD	0.03	0.014	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.023	0.047	-10000	0	-0.42	5	5
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.002	0.085	-10000	0	-0.29	34	34
CFLAR	0.031	0.045	-10000	0	-0.42	5	5
MAPK1	-0.009	0.083	-10000	0	-0.3	38	38
TRAIL/TRAILR1/FADD/TRADD/RIP	0.035	0.09	-10000	0	-0.23	33	33
mol:ceramide	-0.006	0.071	-10000	0	-0.21	44	44
FADD	0.029	0.014	-10000	0	-10000	0	0
MAPK8	-0.022	0.11	-10000	0	-0.35	30	30
TRAF2	0.034	0.029	-10000	0	-0.42	2	2
TRAILR3 (trimer)	0.024	0.026	-10000	0	-0.42	1	1
CHUK	0.026	0.067	-10000	0	-0.42	11	11
TRAIL/TRAILR1/FADD	0.023	0.087	-10000	0	-0.26	34	34
DAP3	0.028	0.025	-10000	0	-0.42	1	1
CASP10	0.014	0.083	0.33	4	-0.29	18	22
JNK cascade	0.01	0.097	-10000	0	-0.29	45	45
TRAIL (trimer)	-0.007	0.13	-10000	0	-0.42	45	45
TNFRSF10C	0.024	0.026	-10000	0	-0.42	1	1
TRAIL/TRAILR1/DAP3/GTP/FADD	0.027	0.075	-10000	0	-0.22	27	27
TRAIL/TRAILR2/FADD	0.025	0.083	-10000	0	-0.26	33	33
cell death	-0.006	0.071	-10000	0	-0.21	44	44
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.001	0.083	-10000	0	-0.28	33	33
TRAILR2 (trimer)	0.027	0.016	-10000	0	-10000	0	0
CASP8	0.025	0.043	-10000	0	-0.66	1	1
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.037	0.086	-10000	0	-0.22	32	32

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.035	0.15	0.23	1	-0.41	41	42
BAG4	0.028	0.025	-10000	0	-0.42	1	1
BAD	-0.007	0.049	0.19	2	-0.16	16	18
NFKBIA	0.033	0.03	-10000	0	-0.42	2	2
BIRC3	-0.008	0.12	-10000	0	-0.42	40	40
BAX	-0.003	0.056	0.2	9	-0.16	15	24
EnzymeConsortium:3.1.4.12	-0.006	0.034	0.075	4	-0.093	34	38
IKBKB	-0.016	0.14	0.3	2	-0.41	29	31
MAP2K2	-0.008	0.055	0.19	11	-0.2	8	19
MAP2K1	-0.007	0.051	0.19	11	-0.19	6	17
SMPD1	-0.006	0.041	-10000	0	-0.16	15	15
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.004	0.15	0.3	5	-0.4	30	35
MAP2K4	-0.015	0.057	0.18	1	-0.19	22	23
protein ubiquitination	-0.032	0.14	0.25	1	-0.41	34	35
EnzymeConsortium:2.7.1.37	-0.011	0.056	0.19	10	-0.2	8	18
response to UV	0	0.001	0.002	12	-0.002	6	18
RAF1	-0.007	0.052	0.2	8	-0.17	10	18
CRADD	0.03	0.05	-10000	0	-0.42	6	6
mol:ceramide	-0.006	0.05	0.11	2	-0.15	27	29
I-kappa-B-alpha/RELA/p50/ubiquitin	0.044	0.023	-10000	0	-0.25	2	2
MADD	0.036	0.005	-10000	0	-10000	0	0
MAP3K1	-0.016	0.06	-10000	0	-0.17	40	40
TRADD	0.03	0.014	-10000	0	-10000	0	0
RELA/p50	0.035	0.006	-10000	0	-10000	0	0
MAPK3	-0.004	0.055	0.19	9	-0.19	5	14
MAPK1	-0.007	0.062	0.19	9	-0.2	13	22
p50/RELA/I-kappa-B-alpha	0.049	0.026	-10000	0	-0.3	2	2
FADD	-0.001	0.15	0.24	13	-0.41	30	43
KSR1	-0.007	0.05	0.19	3	-0.17	14	17
MAPK8	-0.019	0.058	0.21	3	-0.21	11	14
TRAF2	0.034	0.029	-10000	0	-0.42	2	2
response to radiation	0	0	0.002	3	-10000	0	3
CHUK	-0.042	0.14	-10000	0	-0.4	41	41
TNF R/SODD	0.039	0.028	-10000	0	-0.3	1	1
TNF	0.026	0.061	-10000	0	-0.42	9	9
CYCS	0.015	0.069	0.16	28	-0.16	10	38
IKBKG	-0.039	0.14	-10000	0	-0.4	38	38
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.03	0.15	-10000	0	-0.42	39	39
RELA	0.035	0.006	-10000	0	-10000	0	0
RIPK1	0.035	0.008	-10000	0	-10000	0	0
AIFM1	0.012	0.067	0.15	27	-0.16	13	40
TNF/TNF R/SODD	0.048	0.047	-10000	0	-0.25	6	6
TNFRSF1A	0.033	0.022	-10000	0	-0.42	1	1
response to heat	0	0	0.002	3	-10000	0	3
CASP8	0.011	0.12	-10000	0	-0.63	16	16
NSMAF	-0.011	0.14	0.22	23	-0.4	31	54
response to hydrogen peroxide	0	0.001	0.002	12	-0.002	6	18
BCL2	-0.057	0.18	-10000	0	-0.42	99	99

×

Calcium signaling in the CD4+ TCR pathway

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
NFATC1	0.008	0.055	-10000	0	-0.25	16	16
NFATC2	0.014	0.035	-10000	0	-0.27	3	3
NFATC3	0.016	0.026	-10000	0	-10000	0	0
CD40LG	-0.019	0.18	0.38	3	-0.44	52	55
PTGS2	-0.022	0.17	0.38	3	-0.45	43	46
JUNB	0.032	0.041	-10000	0	-0.42	4	4
CaM/Ca2+/Calcineurin A alpha-beta B1	0.021	0.025	-10000	0	-0.11	1	1
CaM/Ca2+	0.021	0.025	-10000	0	-0.11	1	1
CALM1	0.033	0.019	-10000	0	-10000	0	0
JUN	-0.002	0.12	-10000	0	-0.42	39	39
mol:Ca2+	-0.001	0.009	-10000	0	-0.082	1	1
Calcineurin A alpha-beta B1/FKBP12/FK506	0.023	0.01	-10000	0	-10000	0	0
FOSL1	0.035	0.007	-10000	0	-10000	0	0
CREM	0.035	0.007	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	0.016	0.12	-10000	0	-0.33	26	26
FOS	-0.033	0.15	-10000	0	-0.42	66	66
IFNG	-0.035	0.2	0.38	3	-0.51	58	61
AP-1/NFAT1-c-4	0.003	0.22	-10000	0	-0.5	53	53
FASLG	-0.031	0.2	0.38	3	-0.52	52	55
NFAT1-c-4/ICER1	0.028	0.08	0.23	2	-0.24	14	16
IL2RA	-0.029	0.2	0.38	3	-0.48	58	61
FKBP12/FK506	0.026	0.005	-10000	0	-10000	0	0
CSF2	-0.019	0.18	0.38	3	-0.44	51	54
JunB/Fra1/NFAT1-c-4	0.045	0.092	-10000	0	-0.28	9	9
IL4	-0.019	0.18	0.38	3	-0.44	52	55
IL2	0.009	0.15	-10000	0	-1	10	10
IL3	0.02	0.12	-10000	0	-0.7	12	12
FKBP1A	0.035	0.007	-10000	0	-10000	0	0
BATF3	0	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.034	0.017	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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
ARF5/GTP	-0.018	0.059	0.19	12	-0.2	19	31
DAPP1	-0.04	0.16	-10000	0	-0.44	49	49
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.061	0.23	-10000	0	-0.59	59	59
mol:DAG	-0.017	0.092	0.22	4	-0.23	41	45
HRAS	0.031	0.038	-10000	0	-0.42	3	3
RAP1A	0.03	0.047	-10000	0	-0.42	5	5
ARF5/GDP	-0.004	0.11	-10000	0	-0.32	29	29
PLCG2	0.02	0.055	-10000	0	-0.42	7	7
PLCG1	0.034	0.008	-10000	0	-10000	0	0
ARF5	0.034	0.021	-10000	0	-0.42	1	1
mol:GTP	-0.018	0.06	0.19	14	-0.21	19	33
ARF1/GTP	-0.009	0.052	0.2	10	-0.19	19	29
RHOA	0.026	0.061	-10000	0	-0.42	9	9
YES1	0.029	0.05	-10000	0	-0.42	6	6
RAP1A/GTP	-0.017	0.061	0.18	28	-0.21	19	47
ADAP1	-0.018	0.056	0.18	13	-0.2	19	32
ARAP3	-0.018	0.06	0.19	14	-0.21	19	33
INPPL1	0.031	0.036	-10000	0	-0.42	3	3
PREX1	-0.036	0.16	-10000	0	-0.42	75	75
ARHGEF6	0.015	0.093	-10000	0	-0.42	22	22
ARHGEF7	0.032	0.011	-10000	0	-10000	0	0
ARF1	0.027	0.025	-10000	0	-0.42	1	1
NRAS	0.028	0.054	-10000	0	-0.41	7	7
FYN	0.027	0.054	-10000	0	-0.42	7	7
ARF6	0.034	0.029	-10000	0	-0.42	2	2
FGR	0.035	0.008	-10000	0	-10000	0	0
mol:Ca2+	-0.009	0.05	0.15	8	-0.13	20	28
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.028	0.057	-10000	0	-0.42	8	8
ZAP70	0.033	0.022	-10000	0	-0.42	1	1
mol:IP3	-0.016	0.067	0.18	8	-0.18	32	40
LYN	0.03	0.014	-10000	0	-10000	0	0
ARF1/GDP	-0.002	0.1	-10000	0	-0.33	24	24
RhoA/GDP	0.012	0.091	0.23	6	-0.25	25	31
PDK1/Src/Hsp90	0.042	0.025	-10000	0	-0.25	2	2
BLNK	0.013	0.099	-10000	0	-0.42	25	25
actin cytoskeleton reorganization	-0.021	0.11	0.23	5	-0.33	27	32
SRC	0.033	0.029	-10000	0	-0.42	2	2
PLEKHA2	-0.009	0.022	-10000	0	-0.25	4	4
RAC1	0.035	0.006	-10000	0	-10000	0	0
PTEN	0.027	0.059	-10000	0	-0.4	9	9
HSP90AA1	0	0	-10000	0	-10000	0	0
ARF6/GTP	-0.019	0.059	0.2	13	-0.2	19	32
RhoA/GTP	-0.022	0.067	0.17	27	-0.24	23	50
Src family/SYK family/BLNK-LAT	-0.027	0.16	-10000	0	-0.49	40	40
BLK	0.022	0.038	-10000	0	-0.42	3	3
PDPK1	0.032	0.023	-10000	0	-0.42	1	1
CYTH1	-0.018	0.056	0.18	13	-0.2	19	32
HCK	0.018	0.087	-10000	0	-0.42	19	19
CYTH3	-0.018	0.056	0.18	13	-0.2	19	32
CYTH2	-0.018	0.056	0.18	13	-0.2	19	32
KRAS	0.027	0.055	-10000	0	-0.42	7	7
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.006	0.038	0.21	3	-0.2	2	5
SGK1	0.008	0.039	0.24	2	-0.21	2	4
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.02	0.11	-10000	0	-0.34	29	29
SOS1	0.035	0.021	-10000	0	-0.42	1	1
SYK	0.005	0.11	-10000	0	-0.42	34	34
ARF6/GDP	-0.003	0.075	0.22	6	-0.23	21	27
mol:PI-3-4-5-P3	-0.018	0.06	0.22	11	-0.21	19	30
ARAP3/RAP1A/GTP	-0.017	0.061	0.18	28	-0.21	19	47
VAV1	0.019	0.082	-10000	0	-0.42	17	17
mol:PI-3-4-P2	0.006	0.023	-10000	0	-0.3	3	3
RAS family/GTP/PI3K Class I	0.045	0.064	0.21	20	-0.21	19	39
PLEKHA1	-0.011	0.029	-10000	0	-0.25	7	7
Rac1/GDP	-0.003	0.11	-10000	0	-0.33	28	28
LAT	0.03	0.031	-10000	0	-0.42	2	2
Rac1/GTP	-0.018	0.12	-10000	0	-0.35	36	36
ITK	-0.032	0.073	0.19	10	-0.22	47	57
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.028	0.12	0.25	4	-0.32	47	51
LCK	-0.017	0.14	-10000	0	-0.42	54	54
BTK	-0.025	0.068	0.2	10	-0.23	29	39

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.003	0.12	-10000	0	-0.32	51	51
VEGFR1 homodimer/NRP1	-0.017	0.11	-10000	0	-0.31	52	52
mol:DAG	-0.009	0.11	-10000	0	-0.56	9	9
VEGFR1 homodimer/NRP1/VEGFR 121	-0.015	0.098	-10000	0	-0.28	52	52
CaM/Ca2+	0.009	0.11	-10000	0	-0.54	9	9
HIF1A	-0.006	0.14	-10000	0	-0.41	53	53
GAB1	0.027	0.061	-10000	0	-0.42	9	9
AKT1	-0.016	0.11	0.33	1	-0.43	16	17
PLCG1	-0.009	0.11	-10000	0	-0.57	9	9
NOS3	0	0.11	0.48	1	-0.46	17	18
CBL	0.032	0.012	-10000	0	-10000	0	0
mol:NO	0.002	0.11	0.33	4	-0.46	16	20
FLT1	-0.015	0.12	-10000	0	-0.37	47	47
PGF	0.031	0.041	-10000	0	-0.42	4	4
VEGFR1 homodimer/NRP2/VEGFR121	0.002	0.11	-10000	0	-0.29	52	52
CALM1	0.035	0.007	-10000	0	-10000	0	0
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
eNOS/Hsp90	-0.004	0.11	0.24	1	-0.44	16	17
endothelial cell proliferation	-0.002	0.12	0.3	8	-0.49	12	20
mol:Ca2+	-0.009	0.11	-10000	0	-0.56	9	9
MAPK3	-0.024	0.083	0.35	1	-0.48	10	11
MAPK1	-0.028	0.086	0.35	1	-0.49	9	10
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
PLGF homodimer	0.031	0.041	-10000	0	-0.42	4	4
PRKACA	0.036	0.005	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.027	0.054	-10000	0	-0.42	7	7
VEGFA homodimer	0	0	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	-0.017	0.11	-10000	0	-0.31	52	52
platelet activating factor biosynthetic process	-0.005	0.1	0.33	5	-0.45	10	15
PI3K	0.026	0.13	-10000	0	-0.28	61	61
PRKCA	-0.027	0.093	0.21	9	-0.53	9	18
PRKCB	-0.028	0.095	0.18	8	-0.53	9	17
VEGFR1 homodimer/PLGF homodimer	0.002	0.12	-10000	0	-0.31	53	53
VEGFA	0	0	-10000	0	-10000	0	0
VEGFB	0.034	0.021	-10000	0	-0.42	1	1
mol:IP3	-0.009	0.11	-10000	0	-0.56	9	9
RASA1	-0.013	0.11	-10000	0	-0.51	13	13
NRP2	0.034	0.021	-10000	0	-0.42	1	1
VEGFR1 homodimer	-0.015	0.12	-10000	0	-0.37	47	47
VEGFB homodimer	0.034	0.021	-10000	0	-0.42	1	1
NCK1	0.034	0.021	-10000	0	-0.42	1	1
eNOS/Caveolin-1	0.015	0.12	0.36	3	-0.46	18	21
PTPN11	0.036	0.004	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.024	0.13	-10000	0	-0.28	61	61
mol:L-citrulline	0.002	0.11	0.33	4	-0.46	16	20
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.016	0.11	-10000	0	-0.29	41	41
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.002	0.11	-10000	0	-0.28	53	53
CD2AP	0.035	0.007	-10000	0	-10000	0	0
PI3K/GAB1	0.032	0.14	-10000	0	-0.46	14	14
PDPK1	-0.007	0.11	0.35	2	-0.46	12	14
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.003	0.11	-10000	0	-0.28	52	52
mol:NADP	0.002	0.11	0.33	4	-0.46	16	20
HSP90AA1	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.015	0.1	-10000	0	-0.28	41	41
VEGFR1 homodimer/NRP2	0.003	0.12	-10000	0	-0.32	52	52

×

EPHB forward signaling

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
Ephrin A5/EPHB2	0.04	0.038	-10000	0	-0.25	7	7
cell-cell adhesion	0.036	0.06	0.21	45	-10000	0	45
Ephrin B/EPHB2/RasGAP	0.069	0.081	-10000	0	-0.24	23	23
ITSN1	0.034	0.029	-10000	0	-0.42	2	2
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
SHC1	0.028	0.025	-10000	0	-0.42	1	1
Ephrin B1/EPHB3	0.035	0.058	-10000	0	-0.25	19	19
Ephrin B1/EPHB1	0.042	0.036	-10000	0	-0.25	7	7
HRAS/GDP	-0.001	0.11	-10000	0	-0.28	40	40
Ephrin B/EPHB1/GRB7	0.063	0.084	-10000	0	-0.22	30	30
Endophilin/SYNJ1	-0.012	0.053	0.18	14	-0.21	20	34
KRAS	0.028	0.054	-10000	0	-0.42	7	7
Ephrin B/EPHB1/Src	0.07	0.079	-10000	0	-0.24	22	22
endothelial cell migration	0.032	0.094	-10000	0	-0.24	48	48
GRB2	0.033	0.011	-10000	0	-10000	0	0
GRB7	0.024	0.058	-10000	0	-0.42	8	8
PAK1	-0.02	0.067	0.29	2	-0.22	31	33
HRAS	0.032	0.036	-10000	0	-0.42	3	3
RRAS	-0.015	0.057	0.18	13	-0.22	22	35
DNM1	0.033	0.035	-10000	0	-0.42	3	3
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.012	0.058	0.19	8	-0.22	14	22
lamellipodium assembly	-0.036	0.06	-10000	0	-0.21	45	45
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.016	0.069	-10000	0	-0.43	6	6
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
EPHB2	0.032	0.03	-10000	0	-0.42	2	2
EPHB3	0.018	0.085	-10000	0	-0.42	18	18
EPHB1	0.026	0.05	-10000	0	-0.42	6	6
EPHB4	0.016	0.091	-10000	0	-0.42	21	21
mol:GDP	-0.018	0.09	-10000	0	-0.33	25	25
Ephrin B/EPHB2	0.058	0.064	-10000	0	-0.22	19	19
Ephrin B/EPHB3	0.048	0.081	-10000	0	-0.23	32	32
JNK cascade	-0.014	0.059	0.26	9	-0.23	18	27
Ephrin B/EPHB1	0.056	0.068	-10000	0	-0.22	22	22
RAP1/GDP	-0.005	0.11	-10000	0	-0.28	39	39
EFNB2	0.017	0.08	-10000	0	-0.42	16	16
EFNB3	0.032	0.012	-10000	0	-10000	0	0
EFNB1	0.035	0.021	-10000	0	-0.42	1	1
Ephrin B2/EPHB1-2	0.044	0.067	-10000	0	-0.24	23	23
RAP1B	0.033	0.03	-10000	0	-0.42	2	2
RAP1A	0.031	0.045	-10000	0	-0.42	5	5
CDC42/GTP	0.036	0.091	-10000	0	-0.26	23	23
Rap1/GTP	0.015	0.069	-10000	0	-0.25	20	20
axon guidance	0.039	0.038	-10000	0	-0.25	7	7
MAPK3	0.025	0.072	0.2	20	-0.39	6	26
MAPK1	0.016	0.066	0.24	2	-0.39	6	8
Rac1/GDP	-0.017	0.1	-10000	0	-0.29	38	38
actin cytoskeleton reorganization	-0.023	0.076	-10000	0	-0.24	30	30
CDC42/GDP	-0.016	0.1	-10000	0	-0.29	36	36
PI3K	0.038	0.098	-10000	0	-0.24	48	48
EFNA5	0.03	0.046	-10000	0	-0.42	5	5
Ephrin B2/EPHB4	0.02	0.081	-10000	0	-0.26	35	35
Ephrin B/EPHB2/Intersectin/N-WASP	0.011	0.074	-10000	0	-0.24	29	29
CDC42	0.035	0.008	-10000	0	-10000	0	0
RAS family/GTP	0.008	0.067	-10000	0	-0.22	33	33
PTK2	0.11	0.23	0.55	112	-10000	0	112
MAP4K4	-0.015	0.059	0.27	9	-0.23	18	27
SRC	0.033	0.029	-10000	0	-0.42	2	2
KALRN	0.034	0.022	-10000	0	-0.42	1	1
Intersectin/N-WASP	0.045	0.048	-10000	0	-0.3	9	9
neuron projection morphogenesis	-0.013	0.084	0.26	2	-0.3	15	17
MAP2K1	0.01	0.063	0.21	1	-0.41	6	7
WASL	0.029	0.054	-10000	0	-0.42	7	7
Ephrin B1/EPHB1-2/NCK1	0.079	0.05	-10000	0	-0.23	10	10
cell migration	0.027	0.093	0.25	4	-0.39	9	13
NRAS	0.029	0.054	-10000	0	-0.42	7	7
SYNJ1	-0.012	0.053	0.18	14	-0.21	20	34
PXN	0.036	0.004	-10000	0	-10000	0	0
TF	-0.017	0.05	0.17	14	-0.21	16	30
HRAS/GTP	0.042	0.075	-10000	0	-0.22	30	30
Ephrin B1/EPHB1-2	0.058	0.042	-10000	0	-0.23	9	9
cell adhesion mediated by integrin	0.011	0.059	0.22	16	-0.21	12	28
RAC1	0.035	0.006	-10000	0	-10000	0	0
mol:GTP	0.048	0.075	-10000	0	-0.22	28	28
RAC1-CDC42/GTP	-0.033	0.061	-10000	0	-0.23	32	32
RASA1	0.029	0.05	-10000	0	-0.42	6	6
RAC1-CDC42/GDP	-0.003	0.11	-10000	0	-0.28	36	36
ruffle organization	-0.03	0.076	-10000	0	-0.4	5	5
NCK1	0.034	0.021	-10000	0	-0.42	1	1
receptor internalization	-0.019	0.051	0.17	13	-0.2	22	35
Ephrin B/EPHB2/KALRN	0.073	0.074	-10000	0	-0.23	19	19
ROCK1	0.018	0.06	0.19	23	-0.23	19	42
RAS family/GDP	-0.047	0.07	-10000	0	-0.25	31	31
Rac1/GTP	0	0.076	-10000	0	-0.22	45	45
Ephrin B/EPHB1/Src/Paxillin	0.014	0.075	-10000	0	-0.27	23	23

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.014	0.15	0.28	2	-0.44	26	28
PDGFB-D/PDGFRB/SLAP	0.031	0.056	-10000	0	-0.3	11	11
PDGFB-D/PDGFRB/APS/CBL	0.037	0.041	-10000	0	-0.25	8	8
AKT1	-0.01	0.14	0.34	21	-0.39	11	32
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.004	0.14	0.28	1	-0.48	22	23
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
FGR	0.004	0.11	0.32	3	-0.47	16	19
mol:Ca2+	0.006	0.13	0.26	2	-0.49	21	23
MYC	0.01	0.24	0.36	9	-0.72	40	49
SHC1	0.028	0.025	-10000	0	-0.42	1	1
HRAS/GDP	0.034	0.064	0.19	1	-0.22	16	17
LRP1/PDGFRB/PDGFB	0.058	0.06	-10000	0	-0.29	12	12
GRB10	0.023	0.075	-10000	0	-0.42	14	14
PTPN11	0.036	0.004	-10000	0	-10000	0	0
GO:0007205	0.005	0.13	0.26	2	-0.5	21	23
PTEN	0.027	0.061	-10000	0	-0.42	9	9
GRB2	0.033	0.011	-10000	0	-10000	0	0
GRB7	0.024	0.058	-10000	0	-0.42	8	8
PDGFB-D/PDGFRB/SHP2	0.047	0.046	-10000	0	-0.3	8	8
PDGFB-D/PDGFRB/GRB10	0.036	0.073	-10000	0	-0.3	22	22
cell cycle arrest	0.031	0.055	-10000	0	-0.3	11	11
HRAS	0.032	0.036	-10000	0	-0.42	3	3
HIF1A	-0.025	0.13	0.32	19	-0.35	16	35
GAB1	-0.004	0.14	0.32	1	-0.49	25	26
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	-0.005	0.14	0.3	4	-0.44	24	28
PDGFB-D/PDGFRB	0.052	0.055	-10000	0	-0.27	9	9
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.045	0.053	-10000	0	-0.3	11	11
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.01	0.15	0.3	1	-0.43	27	28
positive regulation of MAPKKK cascade	0.046	0.046	-10000	0	-0.3	8	8
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
mol:IP3	0.005	0.13	0.26	2	-0.5	21	23
E5	-0.001	0.002	-10000	0	-10000	0	0
CSK	0.034	0.022	-10000	0	-0.42	1	1
PDGFB-D/PDGFRB/GRB7	0.036	0.064	-10000	0	-0.3	16	16
SHB	0.031	0.046	-10000	0	-0.42	5	5
BLK	-0.065	0.2	0.3	2	-0.43	95	97
PTPN2	0.034	0.01	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.045	0.046	-10000	0	-0.3	8	8
BCAR1	0.03	0.014	-10000	0	-10000	0	0
VAV2	-0.007	0.16	0.29	1	-0.48	30	31
CBL	0.032	0.012	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.042	0.058	-10000	0	-0.3	13	13
LCK	-0.051	0.21	0.3	2	-0.55	67	69
PDGFRB	0.028	0.059	-10000	0	-0.43	8	8
ACP1	0.034	0.035	-10000	0	-0.42	3	3
HCK	-0.003	0.14	0.32	4	-0.53	26	30
ABL1	-0.007	0.13	0.26	1	-0.44	26	27
PDGFB-D/PDGFRB/CBL	-0.011	0.16	-10000	0	-0.55	28	28
PTPN1	0.03	0.031	-10000	0	-0.42	2	2
SNX15	0.035	0.007	-10000	0	-10000	0	0
STAT3	0.028	0.031	-10000	0	-0.42	2	2
STAT1	0.02	0.075	-10000	0	-0.42	14	14
cell proliferation	0.016	0.22	0.35	10	-0.64	40	50
SLA	0.022	0.047	-10000	0	-0.42	5	5
actin cytoskeleton reorganization	0.039	0.071	0.35	4	-0.22	10	14
SRC	0.013	0.094	0.32	3	-0.63	4	7
PI3K	-0.038	0.095	-10000	0	-0.24	82	82
PDGFB-D/PDGFRB/GRB7/SHC	0.042	0.062	-10000	0	-0.26	15	15
SH2B2	0	0	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.004	0.14	0.28	1	-0.49	22	23
LYN	0.015	0.079	0.3	4	-0.36	9	13
LRP1	0.035	0.021	-10000	0	-0.42	1	1
SOS1	0.035	0.021	-10000	0	-0.42	1	1
STAT5B	0.03	0.024	-10000	0	-0.42	1	1
STAT5A	0.027	0.037	-10000	0	-0.42	3	3
NCK1-2/p130 Cas	0.067	0.068	-10000	0	-0.22	9	9
SPHK1	0.006	0.11	-10000	0	-0.42	30	30
EDG1	0.013	0.096	-10000	0	-0.42	23	23
mol:DAG	0.005	0.13	0.26	2	-0.5	21	23
PLCG1	0.005	0.14	0.26	2	-0.52	21	23
NHERF/PDGFRB	0.002	0.13	-10000	0	-0.28	80	80
YES1	-0.004	0.14	0.31	3	-0.52	23	26
cell migration	0.001	0.13	-10000	0	-0.28	80	80
SHC/Grb2/SOS1	0.06	0.068	-10000	0	-0.23	9	9
SLC9A3R2	-0.004	0.12	-10000	0	-0.42	40	40
SLC9A3R1	-0.009	0.13	-10000	0	-0.42	46	46
NHERF1-2/PDGFRB/PTEN	0.011	0.14	-10000	0	-0.27	86	86
FYN	-0.013	0.16	0.31	2	-0.52	33	35
DOK1	0.021	0.071	0.22	16	-0.24	15	31
HRAS/GTP	0.024	0.025	-10000	0	-0.3	3	3
PDGFB	0.029	0.046	-10000	0	-0.42	5	5
RAC1	-0.022	0.2	-10000	0	-0.56	43	43
PRKCD	0.022	0.068	0.2	32	-0.26	10	42
FER	0.024	0.069	0.2	35	-0.24	10	45
MAPKKK cascade	0.043	0.11	0.35	21	-0.22	7	28
RASA1	0.021	0.072	0.21	25	-0.24	14	39
NCK1	0.034	0.021	-10000	0	-0.42	1	1
NCK2	0.036	0.005	-10000	0	-10000	0	0
p62DOK/Csk	0.042	0.065	0.34	2	-0.22	16	18
PDGFB-D/PDGFRB/SHB	0.042	0.058	-10000	0	-0.31	13	13
chemotaxis	-0.006	0.13	0.26	1	-0.43	26	27
STAT1-3-5/STAT1-3-5	0.049	0.075	-10000	0	-0.22	24	24
Bovine Papilomavirus E5/PDGFRB	0.019	0.042	-10000	0	-0.3	8	8
PTPRJ	0.031	0.046	-10000	0	-0.42	5	5

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.009	0.017	-10000	0	-0.26	2	2
RAS family/GTP	0.03	0.11	0.25	1	-0.3	19	20
NFATC4	-0.03	0.068	0.23	1	-0.32	7	8
ERBB2IP	0.034	0.022	-10000	0	-0.42	1	1
HSP90 (dimer)	0	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.003	0.087	-10000	0	-0.26	35	35
JUN	0.008	0.074	0.21	1	-10000	0	1
HRAS	0.032	0.036	-10000	0	-0.42	3	3
DOCK7	-0.034	0.077	0.26	1	-0.27	27	28
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.02	0.089	-10000	0	-0.27	34	34
AKT1	0.003	0.021	-10000	0	-0.3	2	2
BAD	-0.01	0.019	-10000	0	-0.25	3	3
MAPK10	-0.024	0.061	0.2	7	-0.2	16	23
mol:GTP	0	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.002	0.094	-10000	0	-0.28	35	35
RAF1	0.011	0.11	0.28	10	-0.3	21	31
ErbB2/ErbB3/neuregulin 2	0.011	0.093	-10000	0	-0.27	45	45
STAT3	0.005	0.18	-10000	0	-0.89	18	18
cell migration	-0.018	0.064	0.23	8	-0.21	10	18
mol:PI-3-4-5-P3	-0.001	0.001	-10000	0	-10000	0	0
cell proliferation	-0.043	0.25	-10000	0	-0.62	59	59
FOS	-0.045	0.21	0.31	1	-0.44	104	105
NRAS	0.029	0.054	-10000	0	-0.42	7	7
mol:Ca2+	-0.003	0.087	-10000	0	-0.26	35	35
MAPK3	-0.018	0.2	-10000	0	-0.52	47	47
MAPK1	-0.03	0.21	0.35	1	-0.55	49	50
JAK2	-0.032	0.078	0.26	1	-0.26	29	30
NF2	0.01	0.046	-10000	0	-0.68	2	2
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.002	0.072	0.18	3	-0.27	26	29
NRG1	0.028	0.015	-10000	0	-10000	0	0
GRB2/SOS1	0.048	0.023	-10000	0	-0.3	1	1
MAPK8	-0.019	0.098	0.21	3	-0.28	30	33
MAPK9	-0.023	0.058	0.2	6	-0.2	10	16
ERBB2	-0.03	0.055	0.6	1	-0.32	13	14
ERBB3	0.006	0.11	-10000	0	-0.42	32	32
SHC1	0.028	0.025	-10000	0	-0.42	1	1
RAC1	0.035	0.006	-10000	0	-10000	0	0
apoptosis	0.005	0.03	0.33	2	-0.21	4	6
STAT3 (dimer)	0.005	0.17	-10000	0	-0.87	18	18
RNF41	-0.013	0.016	-10000	0	-0.24	2	2
FRAP1	-0.009	0.012	-10000	0	-0.26	1	1
RAC1-CDC42/GTP	-0.015	0.06	-10000	0	-0.2	28	28
ErbB2/ErbB2/HSP90 (dimer)	-0.025	0.04	-10000	0	-0.26	13	13
CHRNA1	-0.004	0.16	0.33	1	-0.41	45	46
myelination	-0.023	0.083	0.26	12	-0.32	7	19
PPP3CB	-0.034	0.072	0.24	1	-0.25	30	31
KRAS	0.028	0.054	-10000	0	-0.42	7	7
RAC1-CDC42/GDP	0.039	0.096	0.25	1	-0.25	25	26
NRG2	0.025	0.061	-10000	0	-0.42	9	9
mol:GDP	0.002	0.072	0.18	3	-0.26	26	29
SOS1	0.035	0.021	-10000	0	-0.42	1	1
MAP2K2	-0.001	0.11	0.26	10	-0.32	25	35
SRC	0.033	0.029	-10000	0	-0.42	2	2
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.035	0.076	0.26	1	-0.26	29	30
MAP2K1	-0.029	0.21	-10000	0	-0.6	33	33
heart morphogenesis	-0.003	0.087	-10000	0	-0.26	35	35
RAS family/GDP	0.041	0.11	0.26	1	-0.29	18	19
GRB2	0.033	0.011	-10000	0	-10000	0	0
PRKACA	0.014	0.054	-10000	0	-0.67	3	3
CHRNE	0.009	0.018	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
activation of caspase activity	-0.003	0.021	0.3	2	-10000	0	2
nervous system development	-0.003	0.087	-10000	0	-0.26	35	35
CDC42	0.035	0.008	-10000	0	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.027	0.1	0.9	1	-0.78	1	2
VDR	0.02	0.082	-10000	0	-0.42	17	17
FAM120B	0	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.004	0.1	-10000	0	-0.27	49	49
RXRs/LXRs/DNA/Oxysterols	0.013	0.16	-10000	0	-0.42	49	49
MED1	0	0	-10000	0	-10000	0	0
mol:9cRA	-0.001	0.019	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	0.004	0.092	-10000	0	-0.24	48	48
RXRs/NUR77	0.055	0.08	-10000	0	-0.25	11	11
RXRs/PPAR	0.009	0.076	-10000	0	-0.26	27	27
NCOR2	0.036	0.005	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.015	0.058	-10000	0	-0.3	17	17
RARs/VDR/DNA/Vit D3	0.053	0.083	-10000	0	-0.23	35	35
RARA	0.03	0.042	-10000	0	-0.42	4	4
NCOA1	0.031	0.045	-10000	0	-0.42	5	5
VDR/VDR/DNA	0.02	0.082	-10000	0	-0.42	17	17
RARs/RARs/DNA/9cRA	0.041	0.063	-10000	0	-0.22	23	23
RARG	0.036	0.005	-10000	0	-10000	0	0
RPS6KB1	0.054	0.15	0.54	42	-10000	0	42
RARs/THRs/DNA/SMRT	0.005	0.09	-10000	0	-0.24	47	47
THRA	0.02	0.075	-10000	0	-0.42	14	14
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.015	0.058	-10000	0	-0.3	17	17
RXRs/PPAR/9cRA/PGJ2/DNA	0.039	0.083	-10000	0	-0.24	15	15
NR1H4	0.035	0.021	-10000	0	-0.42	1	1
RXRs/LXRs/DNA	0.059	0.11	-10000	0	-0.25	14	14
NR1H2	0.029	0.031	-10000	0	-10000	0	0
NR1H3	0.026	0.052	-10000	0	-0.43	4	4
RXRs/VDR/DNA/Vit D3	0.044	0.084	-10000	0	-0.24	19	19
NR4A1	0.034	0.021	-10000	0	-0.42	1	1
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.026	0.063	-10000	0	-0.21	16	16
RXRG	0.017	0.06	-10000	0	-0.43	7	7
RXR alpha/CCPG	0.021	0.029	-10000	0	-0.31	2	2
RXRA	0.028	0.042	-10000	0	-0.44	2	2
RXRB	0.027	0.044	-10000	0	-0.42	2	2
THRB	0.024	0.07	-10000	0	-0.42	12	12
PPARG	0.012	0.093	-10000	0	-0.42	22	22
PPARD	0.036	0.006	-10000	0	-10000	0	0
TNF	-0.001	0.19	-10000	0	-0.78	18	18
mol:Oxysterols	-0.001	0.017	-10000	0	-10000	0	0
cholesterol transport	0.014	0.16	-10000	0	-0.42	49	49
PPARA	0.032	0.03	-10000	0	-0.42	2	2
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.015	0.089	-10000	0	-0.42	20	20
RXRs/NUR77/BCL2	-0.02	0.097	-10000	0	-0.22	84	84
SREBF1	-0.045	0.29	-10000	0	-0.92	46	46
RXRs/RXRs/DNA/9cRA	0.04	0.083	-10000	0	-0.24	16	16
ABCA1	-0.007	0.22	-10000	0	-0.95	17	17
RARs/THRs	0.063	0.1	-10000	0	-0.24	45	45
RXRs/FXR	0.056	0.081	-10000	0	-0.25	12	12
BCL2	-0.057	0.18	-10000	0	-0.42	99	99

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.018	0.14	-9999	-0.33	46	46
MAP3K8	0.003	0.11	-9999	-0.42	32	32
FOS	0.021	0.097	-9999	-0.42	7	7
PRKCA	0.025	0.022	-9999	-10000	0	0
PTPN7	0.02	0.032	-9999	-0.44	1	1
HRAS	0.032	0.036	-9999	-0.42	3	3
PRKCB	-0.002	0.006	-9999	-0.017	73	73
NRAS	0.029	0.054	-9999	-0.42	7	7
RAS family/GTP	0.05	0.055	-9999	-0.23	15	15
MAPK3	0.028	0.067	-9999	-0.44	6	6
MAP2K1	0.009	0.064	-9999	-0.23	8	8
ELK1	0.025	0.038	-9999	-0.42	2	2
BRAF	0.006	0.047	-9999	-0.35	7	7
mol:GTP	-0.001	0.002	-9999	-0.005	73	73
MAPK1	0.013	0.099	-9999	-0.41	18	18
RAF1	0.01	0.023	-9999	-0.24	1	1
KRAS	0.028	0.054	-9999	-0.42	7	7

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.003	0.14	-10000	0	-0.42	2	2
CRKL	0	0.076	0.2	13	-0.23	12	25
mol:DAG	0.019	0.08	0.25	2	-10000	0	2
HRAS	0.023	0.099	0.27	19	-10000	0	19
MAPK8	0.037	0.073	0.2	56	-0.25	2	58
RAP1A	0.001	0.077	0.24	5	-0.23	12	17
GAB1	0	0.076	0.23	4	-0.24	12	16
MAPK14	0.037	0.071	0.2	54	-10000	0	54
EPO	0.023	0.027	-10000	0	-10000	0	0
PLCG1	0.019	0.081	0.25	2	-10000	0	2
EPOR/TRPC2/IP3 Receptors	0.026	0.028	-10000	0	-10000	0	0
RAPGEF1	0.036	0.004	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.046	0.052	-10000	0	-0.27	4	4
GAB1/SHC/GRB2/SOS1	0.029	0.075	0.29	1	-0.2	8	9
EPO/EPOR (dimer)	0.037	0.039	-10000	0	-10000	0	0
IRS2	-0.009	0.087	0.21	10	-0.25	30	40
STAT1	-0.003	0.13	0.26	2	-0.28	63	65
STAT5B	0.021	0.081	0.26	1	-0.26	2	3
cell proliferation	0.014	0.079	0.19	76	-0.24	2	78
GAB1/SHIP/PIK3R1/SHP2/SHC	0.009	0.074	-10000	0	-0.21	22	22
TEC	0.001	0.076	0.25	4	-0.22	12	16
SOCS3	0.028	0.046	-10000	0	-0.42	5	5
STAT1 (dimer)	-0.001	0.13	0.26	2	-0.28	63	65
JAK2	0.028	0.036	-10000	0	-0.44	2	2
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
EPO/EPOR (dimer)/JAK2	0.036	0.089	0.22	3	-0.17	40	43
EPO/EPOR	0.037	0.039	-10000	0	-10000	0	0
LYN	0.021	0.027	-10000	0	-10000	0	0
TEC/VAV2	0.016	0.081	0.29	2	-0.22	11	13
elevation of cytosolic calcium ion concentration	0.026	0.028	-10000	0	-10000	0	0
SHC1	0.028	0.025	-10000	0	-0.42	1	1
EPO/EPOR (dimer)/LYN	0.044	0.053	-10000	0	-10000	0	0
mol:IP3	0.019	0.08	0.25	2	-10000	0	2
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.005	0.095	0.29	1	-0.23	43	44
SH2B3	-0.003	0.009	-10000	0	-10000	0	0
NFKB1	0.038	0.072	0.2	56	-10000	0	56
EPO/EPOR (dimer)/JAK2/SOCS3	0.023	0.035	-10000	0	-0.21	6	6
PTPN6	-0.002	0.068	0.17	9	-0.18	26	35
TEC/VAV2/GRB2	0.028	0.084	0.3	2	-0.21	7	9
EPOR	0.026	0.028	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.028	0.076	0.3	1	-0.2	8	9
SOS1	0.035	0.021	-10000	0	-0.42	1	1
PLCG2	0.02	0.055	-10000	0	-0.42	7	7
CRKL/CBL/C3G	0.021	0.085	0.3	1	-0.23	10	11
VAV2	0.003	0.074	0.24	5	-0.24	7	12
CBL	0	0.071	0.23	4	-0.24	7	11
SHC/Grb2/SOS1	0.015	0.063	-10000	0	-0.2	5	5
STAT5A	0.019	0.082	0.26	1	-0.26	3	4
GRB2	0.033	0.011	-10000	0	-10000	0	0
STAT5 (dimer)	0.018	0.12	0.28	1	-0.31	44	45
LYN/PLCgamma2	0.03	0.043	-10000	0	-0.3	6	6
PTPN11	0.036	0.004	-10000	0	-10000	0	0
BTK	-0.003	0.083	0.24	5	-0.24	20	25
BCL2	-0.11	0.33	-10000	0	-0.73	105	105

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.027	0.032	-9999	-0.42	2	2
Syndecan-3/Src/Cortactin	0.007	0.15	-9999	-0.48	27	27
Syndecan-3/Neurocan	-0.018	0.12	-9999	-0.48	30	30
POMC	0.032	0.036	-9999	-0.42	3	3
EGFR	-0.015	0.13	-9999	-0.42	49	49
Syndecan-3/EGFR	-0.011	0.15	-9999	-0.51	31	31
AGRP	0.029	0.025	-9999	-0.42	1	1
NCSTN	0.028	0.025	-9999	-0.42	1	1
PSENEN	0.035	0.006	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.025	0.067	-9999	-0.42	11	11
APH1A	0.031	0.036	-9999	-0.42	3	3
NCAN	0	0	-9999	-10000	0	0
long-term memory	0.018	0.12	-9999	-0.44	28	28
Syndecan-3/IL8	-0.007	0.14	-9999	-0.52	30	30
PSEN1	0.032	0.041	-9999	-0.42	4	4
Src/Cortactin	0.039	0.038	-9999	-0.3	4	4
FYN	0.027	0.054	-9999	-0.42	7	7
limb bud formation	-0.015	0.12	-9999	-0.53	26	26
MC4R	0.034	0.022	-9999	-0.42	1	1
SRC	0.033	0.029	-9999	-0.42	2	2
PTN	-0.029	0.15	-9999	-0.42	65	65
FGFR/FGF/Syndecan-3	-0.015	0.12	-9999	-0.53	26	26
neuron projection morphogenesis	-0.031	0.12	-9999	-0.48	25	25
Syndecan-3/AgRP	0.009	0.13	-9999	-0.47	30	30
Syndecan-3/AgRP/MC4R	0.024	0.13	-9999	-0.48	27	27
Fyn/Cortactin	0.035	0.044	-9999	-0.3	6	6
SDC3	-0.016	0.12	-9999	-0.54	26	26
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.006	0.14	-9999	-0.51	30	30
IL8	-0.004	0.12	-9999	-0.42	37	37
Syndecan-3/Fyn/Cortactin	0.019	0.13	-9999	-0.45	28	28
Syndecan-3/CASK	-0.018	0.12	-9999	-0.48	30	30
alpha-MSH/MC4R	0.047	0.034	-9999	-0.3	4	4
Gamma Secretase	0.069	0.069	-9999	-0.22	13	13

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.072	0.23	-10000	0	-0.78	21	21
RAD9A	0.034	0.01	-10000	0	-10000	0	0
AP1	-0.025	0.15	-10000	0	-0.34	88	88
IFNAR2	0.028	0.03	-10000	0	-0.43	1	1
AKT1	-0.034	0.11	-10000	0	-0.24	60	60
ER alpha/Oestrogen	-0.063	0.14	-10000	0	-0.3	132	132
NFX1/SIN3/HDAC complex	0.012	0.072	-10000	0	-0.35	12	12
EGF	-0.069	0.19	-10000	0	-0.42	110	110
SMG5	0	0	-10000	0	-10000	0	0
SMG6	0	0	-10000	0	-10000	0	0
SP3/HDAC2	0.039	0.037	-10000	0	-0.3	1	1
TERT/c-Abl	-0.061	0.22	-10000	0	-0.72	21	21
SAP18	0.033	0.01	-10000	0	-10000	0	0
MRN complex	0.048	0.044	-10000	0	-0.26	4	4
WT1	-0.025	0.14	-10000	0	-0.42	54	54
WRN	0.027	0.025	-10000	0	-0.42	1	1
SP1	0.026	0.033	-10000	0	-0.43	1	1
SP3	0.035	0.007	-10000	0	-10000	0	0
TERF2IP	0.03	0.014	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.046	0.21	-10000	0	-0.63	24	24
Mad/Max	0.048	0.019	-10000	0	-10000	0	0
TERT	-0.075	0.24	-10000	0	-0.82	21	21
CCND1	-0.15	0.44	-10000	0	-1.1	85	85
MAX	0.034	0.009	-10000	0	-10000	0	0
RBBP7	0.034	0.029	-10000	0	-0.42	2	2
RBBP4	0.034	0.021	-10000	0	-0.42	1	1
TERF2	0.027	0.031	-10000	0	-0.36	2	2
PTGES3	0.035	0.021	-10000	0	-0.42	1	1
SIN3A	0.035	0.007	-10000	0	-10000	0	0
Telomerase/911	0.021	0.069	-10000	0	-0.46	5	5
CDKN1B	-0.028	0.14	-10000	0	-0.37	66	66
RAD1	0.033	0.029	-10000	0	-0.42	2	2
XRCC5	0.036	0.005	-10000	0	-10000	0	0
XRCC6	0.034	0.009	-10000	0	-10000	0	0
SAP30	0.03	0.046	-10000	0	-0.42	5	5
TRF2/PARP2	0.043	0.032	-10000	0	-0.28	2	2
UBE3A	0.034	0.029	-10000	0	-0.42	2	2
JUN	-0.002	0.12	-10000	0	-0.42	39	39
E6	-0.001	0.004	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.02	0.027	-10000	0	-0.3	2	2
FOS	-0.032	0.15	-10000	0	-0.42	66	66
IFN-gamma/IRF1	0.001	0.12	-10000	0	-0.3	70	70
PARP2	0.036	0.002	-10000	0	-10000	0	0
BLM	0.012	0.097	-10000	0	-0.42	24	24
Telomerase	0.012	0.044	0.18	1	-0.15	1	2
IRF1	0.016	0.083	-10000	0	-0.26	34	34
ESR1	-0.089	0.2	-10000	0	-0.42	132	132
KU/TER	0.05	0.015	-10000	0	-10000	0	0
ATM/TRF2	0.036	0.035	-10000	0	-0.18	2	2
ubiquitin-dependent protein catabolic process	0.023	0.06	-10000	0	-0.27	11	11
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.025	0.056	-10000	0	-0.28	7	7
HDAC1	0.034	0.021	-10000	0	-0.42	1	1
HDAC2	0.025	0.032	-10000	0	-0.42	1	1
ATM	0.02	0.025	0.19	2	-10000	0	2
SMAD3	0.011	0.044	-10000	0	-0.3	10	10
ABL1	0.036	0.005	-10000	0	-10000	0	0
MXD1	0.035	0.007	-10000	0	-10000	0	0
MRE11A	0.031	0.013	-10000	0	-10000	0	0
HUS1	0.035	0.006	-10000	0	-10000	0	0
RPS6KB1	0.031	0.013	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.058	0.23	-10000	0	-0.74	22	22
NR2F2	-0.01	0.14	-10000	0	-0.42	49	49
MAPK3	0.008	0.032	-10000	0	-0.3	4	4
MAPK1	0.008	0.032	-10000	0	-0.3	4	4
TGFB1/TGF beta receptor Type II	0.035	0.021	-10000	0	-0.42	1	1
NFKB1	0.036	0.005	-10000	0	-10000	0	0
HNRNPC	0	0	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.02	0.025	0.19	2	-10000	0	2
NBN	0.028	0.025	-10000	0	-0.42	1	1
EGFR	-0.015	0.13	-10000	0	-0.42	49	49
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.063	0.16	-10000	0	-0.31	152	152
MYC	-0.002	0.1	-10000	0	-0.42	29	29
IL2	0.024	0.043	-10000	0	-0.42	3	3
KU	0.05	0.015	-10000	0	-10000	0	0
RAD50	0.032	0.041	-10000	0	-0.42	4	4
HSP90AA1	0	0	-10000	0	-10000	0	0
TGFB1	0.035	0.021	-10000	0	-0.42	1	1
TRF2/BLM	0.026	0.073	-10000	0	-0.28	25	25
FRAP1	0.035	0.007	-10000	0	-10000	0	0
KU/TERT	-0.049	0.23	-10000	0	-0.72	22	22
SP1/HDAC2	0.038	0.043	-10000	0	-0.3	2	2
PINX1	0.028	0.015	-10000	0	-10000	0	0
Telomerase/EST1A	-0.059	0.2	-10000	0	-0.62	25	25
Smad3/Myc	0.006	0.074	-10000	0	-0.25	35	35
911 complex	0.063	0.032	-10000	0	-0.26	2	2
IFNG	-0.014	0.12	-10000	0	-0.34	56	56
Telomerase/PinX1	-0.057	0.2	-10000	0	-0.63	24	24
Telomerase/AKT1/mTOR/p70S6K	-0.006	0.1	-10000	0	-0.43	15	15
SIN3B	0.036	0.005	-10000	0	-10000	0	0
YWHAE	0.032	0.012	-10000	0	-10000	0	0
Telomerase/EST1B	-0.059	0.2	-10000	0	-0.62	25	25
response to DNA damage stimulus	-0.001	0.033	0.13	1	-0.1	35	36
MRN complex/TRF2/Rap1	0.059	0.061	-10000	0	-0.27	4	4
TRF2/WRN	0.034	0.036	-10000	0	-0.28	3	3
Telomerase/hnRNP C1/C2	-0.059	0.2	-10000	0	-0.62	25	25
E2F1	0.021	0.057	-10000	0	-0.42	7	7
ZNFX1	0	0.001	-10000	0	-10000	0	0
PIF1	0	0	-10000	0	-10000	0	0
NCL	0.036	0.006	-10000	0	-10000	0	0
DKC1	0.036	0.003	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Aurora A signaling

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
Aurora A/GADD45A	0.032	0.055	-10000	0	-0.24	15	15
BIRC5	-0.002	0.12	-10000	0	-0.42	38	38
NFKBIA	0.018	0.051	0.25	15	-0.25	2	17
CPEB1	0.03	0.046	-10000	0	-0.42	5	5
AKT1	0.014	0.041	0.25	7	-0.25	2	9
NDEL1	0.032	0.012	-10000	0	-10000	0	0
Aurora A/BRCA1	0.028	0.047	-10000	0	-0.23	12	12
NDEL1/TACC3	0.042	0.049	-10000	0	-0.16	17	17
GADD45A	0.019	0.08	-10000	0	-0.42	16	16
GSK3B	0.039	0.016	-10000	0	-10000	0	0
PAK1/Aurora A	0.028	0.06	-10000	0	-0.24	18	18
MDM2	0.034	0.009	-10000	0	-10000	0	0
JUB	0.003	0.12	-10000	0	-0.42	35	35
TPX2	-0.007	0.083	-10000	0	-0.3	37	37
TP53	-0.004	0.093	-10000	0	-0.23	67	67
DLG7	-0.006	0.06	0.25	5	-0.18	39	44
AURKAIP1	0	0	-10000	0	-10000	0	0
ARHGEF7	0.032	0.011	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.045	0.052	-10000	0	-0.17	17	17
G2/M transition of mitotic cell cycle	0.028	0.047	-10000	0	-0.22	12	12
AURKA	0.024	0.035	0.14	41	-10000	0	41
AURKB	0.001	0.06	-10000	0	-0.18	43	43
CDC25B	0.014	0.048	-10000	0	-0.29	5	5
G2/M transition checkpoint	0.018	0.069	-10000	0	-0.22	35	35
mRNA polyadenylation	0.033	0.035	-10000	0	-0.2	5	5
Aurora A/CPEB	0.033	0.035	-10000	0	-0.2	5	5
Aurora A/TACC1/TRAP/chTOG	0.05	0.078	-10000	0	-0.23	23	23
BRCA1	0.022	0.07	-10000	0	-0.42	12	12
centrosome duplication	0.028	0.06	-10000	0	-0.24	18	18
regulation of centrosome cycle	0.041	0.048	-10000	0	-0.16	17	17
spindle assembly	0.048	0.076	-10000	0	-0.23	23	23
TDRD7	0.027	0.064	-10000	0	-0.42	10	10
Aurora A/RasGAP/Survivin	0.034	0.08	-10000	0	-0.21	27	27
CENPA	-0.005	0.084	-10000	0	-0.27	43	43
Aurora A/PP2A	0.042	0.029	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.001	0.044	0.17	5	-0.24	1	6
negative regulation of DNA binding	-0.006	0.097	-10000	0	-0.24	68	68
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.046	0.024	-10000	0	-0.3	1	1
RASA1	0.029	0.05	-10000	0	-0.42	6	6
Ajuba/Aurora A	0.019	0.069	-10000	0	-0.22	35	35
mitotic prometaphase	0.004	0.024	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.035	0.14	41	-10000	0	41
TACC1	0.011	0.089	-10000	0	-0.42	20	20
TACC3	0.017	0.087	-10000	0	-0.42	19	19
Aurora A/Antizyme1	0.037	0.025	-10000	0	-10000	0	0
Aurora A/RasGAP	0.038	0.042	-10000	0	-0.25	6	6
OAZ1	0.035	0.006	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.039	0.016	-10000	0	-10000	0	0
GIT1	0.034	0.022	-10000	0	-0.42	1	1
GIT1/beta-PIX/PAK1	0.044	0.068	-10000	0	-0.27	18	18
Importin alpha/Importin beta/TPX2	-0.007	0.082	-10000	0	-0.3	37	37
PPP2R5D	0.035	0.006	-10000	0	-10000	0	0
Aurora A/TPX2	0.008	0.052	-10000	0	-0.16	37	37
PAK1	0.015	0.085	-10000	0	-0.42	18	18
CKAP5	0.036	0.006	-10000	0	-10000	0	0

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	0.047	0.04	-10000	0	-0.3	6	6
Necdin/E2F1	0.013	0.11	-10000	0	-0.31	54	54
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.031	0.11	-10000	0	-0.23	70	70
NGF (dimer)/p75(NTR)/BEX1	0.038	0.035	-10000	0	-0.25	6	6
NT-4/5 (dimer)/p75(NTR)	0.022	0.026	-10000	0	-0.3	3	3
IKBKB	0.03	0.014	-10000	0	-10000	0	0
AKT1	0.021	0.069	0.19	43	-0.22	20	63
IKBKG	0.036	0	-10000	0	-10000	0	0
BDNF	0.031	0.024	-10000	0	-0.42	1	1
MGDIs/NGR/p75(NTR)/LINGO1	0.034	0.049	-10000	0	-0.25	13	13
FURIN	0.027	0.057	-10000	0	-0.42	8	8
proBDNF (dimer)/p75(NTR)/Sortilin	0.058	0.047	-10000	0	-0.25	9	9
LINGO1	0	0	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	0.026	0.054	-10000	0	-0.22	17	17
proBDNF (dimer)	0.031	0.024	-10000	0	-0.42	1	1
NTRK1	0.026	0.032	-10000	0	-0.42	2	2
RTN4R	0.024	0.067	-10000	0	-0.42	11	11
neuron apoptosis	-0.008	0.1	0.28	1	-0.44	10	11
IRAK1	0.036	0.004	-10000	0	-10000	0	0
SHC1	0.012	0.022	-10000	0	-0.25	3	3
ARHGDIA	0.033	0.022	-10000	0	-0.42	1	1
RhoA/GTP	0.02	0.043	-10000	0	-0.3	9	9
Gamma Secretase	0.069	0.069	-10000	0	-0.22	13	13
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.04	0.083	-10000	0	-0.24	38	38
MAGEH1	0.006	0.11	-10000	0	-0.42	34	34
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.03	0.097	-10000	0	-0.24	54	54
Mammalian IAPs/DIABLO	0.034	0.082	-10000	0	-0.23	39	39
proNGF (dimer)	0	0	-10000	0	-10000	0	0
MAGED1	0.015	0.095	-10000	0	-0.42	23	23
APP	0.008	0.11	-10000	0	-0.42	29	29
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
ZNF274	0.034	0.029	-10000	0	-0.42	2	2
RhoA/GDP/RHOGDI	0.038	0.045	0.18	4	-0.21	12	16
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	-0.01	0.05	0.2	18	-0.21	9	27
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.021	0.031	-10000	0	-0.21	6	6
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.042	0.03	-10000	0	-0.25	4	4
NCSTN	0.028	0.025	-10000	0	-0.42	1	1
mol:GTP	0.025	0.068	-10000	0	-0.25	28	28
PSENEN	0.035	0.006	-10000	0	-10000	0	0
mol:ceramide	0.016	0.044	0.19	13	-0.23	10	23
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.013	0.036	-10000	0	-10000	0	0
p75(NTR)/beta APP	0.026	0.084	-10000	0	-0.3	30	30
BEX1	0.027	0.037	-10000	0	-0.42	3	3
mol:GDP	-0.006	0.019	-10000	0	-0.25	3	3
NGF (dimer)	0.008	0.11	-10000	0	-0.23	76	76
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.049	0.054	-10000	0	-0.23	14	14
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
RAC1/GTP	0.037	0.023	-10000	0	-0.21	3	3
MYD88	0.031	0.041	-10000	0	-0.42	4	4
CHUK	0.026	0.067	-10000	0	-0.42	11	11
NGF (dimer)/p75(NTR)/PKA	0.025	0.069	-10000	0	-0.25	28	28
RHOB	-0.011	0.14	-10000	0	-0.42	52	52
RHOA	0.026	0.061	-10000	0	-0.42	9	9
MAGE-G1/E2F1	0.045	0.043	-10000	0	-0.3	7	7
NT3 (dimer)	0.023	0.058	-10000	0	-0.42	8	8
TP53	-0.019	0.066	0.24	3	-0.22	24	27
PRDM4	0.02	0.046	0.19	18	-0.23	9	27
BDNF (dimer)	-0.018	0.16	-10000	0	-0.31	110	110
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
SORT1	0.03	0.05	-10000	0	-0.42	6	6
activation of caspase activity	0.025	0.11	-10000	0	-0.23	70	70
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.057	0.044	-10000	0	-0.23	9	9
RHOC	0.033	0.036	-10000	0	-0.42	3	3
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	-0.016	0.079	0.22	1	-0.29	13	14
DIABLO	0.036	0.004	-10000	0	-10000	0	0
SMPD2	0.016	0.045	0.19	13	-0.23	10	23
APH1B	0.025	0.067	-10000	0	-0.42	11	11
APH1A	0.031	0.036	-10000	0	-0.42	3	3
proNGF (dimer)/p75(NTR)/Sortilin	0.039	0.041	-10000	0	-0.25	9	9
PSEN1	0.032	0.041	-10000	0	-0.42	4	4
APAF-1/Pro-Caspase 9	0.047	0.037	-10000	0	-0.3	5	5
NT3 (dimer)/p75(NTR)	0.037	0.053	-10000	0	-0.3	11	11
MAPK8	-0.01	0.066	-10000	0	-0.27	7	7
MAPK9	-0.015	0.078	-10000	0	-0.32	11	11
APAF1	0.032	0.041	-10000	0	-0.42	4	4
NTF3	0.023	0.058	-10000	0	-0.42	8	8
NTF4	0	0	-10000	0	-10000	0	0
NDN	-0.012	0.14	-10000	0	-0.42	53	53
RAC1/GDP	0.026	0.004	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.018	0.11	-10000	0	-0.22	85	85
p75 CTF/Sortilin/TRAF6/NRIF	0.082	0.047	-10000	0	-0.23	8	8
RhoA-B-C/GTP	0.024	0.068	-10000	0	-0.25	28	28
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.086	0.059	-10000	0	-0.22	12	12
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.074	0.052	-10000	0	-0.23	10	10
PRKACB	0.008	0.099	-10000	0	-0.42	25	25
proBDNF (dimer)/p75 ECD	0.048	0.02	-10000	0	-0.3	1	1
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.008	0.12	-10000	0	-0.42	40	40
BIRC2	0.032	0.012	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.038	0.08	-10000	0	-0.26	38	38
BAD	-0.02	0.079	-10000	0	-0.29	10	10
RIPK2	0.028	0.015	-10000	0	-10000	0	0
NGFR	0.03	0.036	-10000	0	-0.42	3	3
CYCS	0.005	0.064	0.19	13	-0.22	32	45
ADAM17	0.036	0.006	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.048	0.04	-10000	0	-0.23	4	4
BCL2L11	-0.019	0.079	-10000	0	-0.29	10	10
BDNF (dimer)/p75(NTR)	0.044	0.034	-10000	0	-0.3	4	4
PI3K	0.046	0.061	-10000	0	-0.23	19	19
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.056	0.045	-10000	0	-0.23	9	9
NDNL2	0.035	0.008	-10000	0	-10000	0	0
YWHAE	0.032	0.012	-10000	0	-10000	0	0
PRKCI	0.025	0.064	-10000	0	-0.42	10	10
NGF (dimer)/p75(NTR)	0.022	0.026	-10000	0	-0.3	3	3
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.045	0.074	-10000	0	-0.23	32	32
TRAF6	0.035	0.021	-10000	0	-0.42	1	1
RAC1	0.035	0.006	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
PLG	0.032	0.03	-10000	0	-0.42	2	2
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	0.018	0.046	-10000	0	-0.24	14	14
SQSTM1	0.034	0.021	-10000	0	-0.42	1	1
NGFRAP1	-0.025	0.16	-10000	0	-0.42	68	68
CASP3	-0.018	0.077	-10000	0	-0.27	10	10
E2F1	0.029	0.054	-10000	0	-0.42	7	7
CASP9	0.034	0.022	-10000	0	-0.42	1	1
IKK complex	0.042	0.064	-10000	0	-0.31	1	1
NGF (dimer)/TRKA	0.019	0.023	-10000	0	-0.3	2	2
MMP7	-0.032	0.15	-10000	0	-0.42	68	68
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.07	0.051	-10000	0	-0.22	11	11
MMP3	-0.045	0.16	-10000	0	-0.42	81	81
APAF-1/Caspase 9	-0.04	0.065	-10000	0	-0.2	54	54

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.035	0.006	-10000	0	-10000	0	0
VLDLR	-0.007	0.12	-10000	0	-0.42	42	42
LRPAP1	0.035	0.007	-10000	0	-10000	0	0
NUDC	0.035	0.007	-10000	0	-10000	0	0
RELN/LRP8	0.039	0.089	-10000	0	-0.25	40	40
CaM/Ca2+	0.026	0.005	-10000	0	-10000	0	0
KATNA1	0.033	0.01	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	0.001	0.073	0.19	10	-0.23	40	50
IQGAP1/CaM	0.05	0.015	-10000	0	-10000	0	0
DAB1	0.035	0.007	-10000	0	-10000	0	0
IQGAP1	0.035	0.008	-10000	0	-10000	0	0
PLA2G7	-0.035	0.16	-10000	0	-0.42	74	74
CALM1	0.035	0.007	-10000	0	-10000	0	0
DYNLT1	0.034	0.01	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.024	0.089	-10000	0	-0.3	35	35
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0	0	-10000	0	-10000	0	0
CDK5R1	0.033	0.01	-10000	0	-10000	0	0
LIS1/Poliovirus Protein 3A	0.011	0.012	-10000	0	-0.25	1	1
CDK5R2	0.036	0.005	-10000	0	-10000	0	0
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	0.033	0.097	-10000	0	-0.26	46	46
YWHAE	0.032	0.012	-10000	0	-10000	0	0
NDEL1/14-3-3 E	0.016	0.07	0.33	1	-0.24	4	5
MAP1B	-0.009	0.064	-10000	0	-0.26	30	30
RAC1	0.016	0.007	-10000	0	-10000	0	0
p35/CDK5	0.008	0.067	0.2	2	-0.21	38	40
RELN	0.03	0.046	-10000	0	-0.42	5	5
PAFAH/LIS1	-0.01	0.1	-10000	0	-0.25	74	74
LIS1/CLIP170	0.011	0.012	-10000	0	-0.25	1	1
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	0.018	0.068	-10000	0	-0.23	1	1
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.009	0.1	-10000	0	-0.26	61	61
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.002	0.062	0.33	1	-0.26	4	5
LIS1/IQGAP1	0.034	0.014	-10000	0	-10000	0	0
RHOA	0.008	0.056	-10000	0	-0.4	9	9
PAFAH1B1	0.014	0.015	-10000	0	-0.3	1	1
PAFAH1B3	0.03	0.054	-10000	0	-0.42	7	7
PAFAH1B2	0.031	0.013	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.015	0.061	-10000	0	-0.18	32	32
NDEL1/Katanin 60/Dynein heavy chain	0.023	0.08	0.37	2	-0.25	4	6
LRP8	-0.001	0.12	-10000	0	-0.42	35	35
NDEL1/Katanin 60	0.009	0.072	0.33	1	-0.25	4	5
P39/CDK5	0.009	0.068	0.2	2	-0.21	40	42
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.033	0.019	-10000	0	-0.26	1	1
CDK5	-0.026	0.063	0.18	9	-0.22	40	49
PPP2R5D	0.035	0.006	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.009	0.011	-10000	0	-0.21	1	1
CSNK2A1	0.035	0.006	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	0.035	0.091	-10000	0	-0.23	46	46
RELN/VLDLR	0.025	0.12	-10000	0	-0.24	80	80
CDC42	0.016	0.007	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	-0.007	0.28	-10000	0	-1	33	33
oxygen homeostasis	0.005	0.01	-10000	0	-10000	0	0
TCEB2	0.033	0.011	-10000	0	-10000	0	0
TCEB1	0.028	0.025	-10000	0	-0.42	1	1
VHL/Elongin B/Elongin C/HIF2A	0.054	0.11	0.28	2	-0.33	11	13
EPO	0.072	0.18	-10000	0	-0.52	16	16
FIH (dimer)	0.037	0.02	-10000	0	-10000	0	0
APEX1	0.035	0.028	-10000	0	-10000	0	0
SERPINE1	0.056	0.2	-10000	0	-0.55	27	27
FLT1	-0.043	0.28	-10000	0	-0.84	42	42
ADORA2A	0.044	0.18	-10000	0	-0.53	24	24
germ cell development	0.064	0.18	-10000	0	-0.52	20	20
SLC11A2	0.065	0.19	-10000	0	-0.55	21	21
BHLHE40	0.053	0.18	0.33	1	-0.49	26	27
HIF1AN	0.038	0.02	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.073	0.15	0.33	1	-0.38	20	21
ETS1	0.037	0.033	-10000	0	-0.42	1	1
CITED2	0.016	0.18	-10000	0	-0.84	16	16
KDR	-0.015	0.24	-10000	0	-0.74	35	35
PGK1	0.066	0.19	-10000	0	-0.53	21	21
SIRT1	0.036	0.006	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	0.11	0.23	-10000	0	-0.61	21	21
EPAS1	0.027	0.12	-10000	0	-0.33	24	24
SP1	0.033	0.039	-10000	0	-0.42	1	1
ABCG2	0.061	0.2	-10000	0	-0.56	23	23
EFNA1	0.032	0.19	-10000	0	-0.51	33	33
FXN	0.052	0.18	0.35	1	-0.52	20	21
POU5F1	0.064	0.19	-10000	0	-0.54	20	20
neuron apoptosis	-0.1	0.22	0.59	21	-10000	0	21
EP300	0.032	0.03	-10000	0	-0.42	2	2
EGLN3	-0.012	0.14	-10000	0	-0.42	52	52
EGLN2	0.034	0.045	-10000	0	-0.41	4	4
EGLN1	0.023	0.057	-10000	0	-0.42	7	7
VHL/Elongin B/Elongin C	0.054	0.036	-10000	0	-0.26	1	1
VHL	0.035	0.007	-10000	0	-10000	0	0
ARNT	0.035	0.027	-10000	0	-10000	0	0
SLC2A1	0.046	0.18	0.34	4	-0.52	24	28
TWIST1	0.038	0.21	0.35	1	-0.58	35	36
ELK1	0.039	0.032	-10000	0	-0.32	3	3
HIF2A/ARNT/Cbp/p300	0.071	0.15	0.34	1	-0.39	17	18
VEGFA	0.053	0.18	0.33	1	-0.49	26	27
CREBBP	0.033	0.011	-10000	0	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.028	0.057	-10000	0	-0.42	8	8
mol:S1P	0.001	0.002	-10000	0	-0.025	3	3
S1P1/S1P/Gi	-0.016	0.11	-10000	0	-0.29	47	47
GNAO1	0.031	0.015	-10000	0	-10000	0	0
S1P/S1P3/G12/G13	0.039	0.028	-10000	0	-0.23	3	3
AKT1	0.003	0.12	-10000	0	-0.46	29	29
AKT3	-0.004	0.12	-10000	0	-0.6	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.028	0.057	-10000	0	-0.42	8	8
GNAI2	0.029	0.054	-10000	0	-0.42	7	7
GNAI3	0.036	0.008	-10000	0	-10000	0	0
GNAI1	0.018	0.087	-10000	0	-0.42	19	19
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.001	0.002	-10000	0	-0.03	3	3
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	0.013	0.095	-10000	0	-0.42	23	23
mol:Ca2+	0.006	0.083	-10000	0	-0.24	41	41
MAPK3	-0.002	0.074	-10000	0	-0.3	17	17
MAPK1	0	0.076	-10000	0	-0.23	38	38
JAK2	-0.014	0.1	0.22	1	-0.32	33	34
CXCR4	-0.013	0.1	-10000	0	-0.29	39	39
FLT1	0.027	0.058	-10000	0	-0.42	8	8
RhoA/GDP	0.02	0.043	-10000	0	-0.3	9	9
Rac1/GDP	0.026	0.004	-10000	0	-10000	0	0
SRC	-0.004	0.081	-10000	0	-0.33	17	17
S1P/S1P3/Gi	0.006	0.083	-10000	0	-0.24	41	41
RAC1	0.035	0.006	-10000	0	-10000	0	0
RhoA/GTP	0.005	0.096	-10000	0	-0.27	30	30
VEGFA	0.002	0.003	-10000	0	-0.04	3	3
S1P/S1P2/Gi	0.004	0.08	-10000	0	-0.24	40	40
VEGFR1 homodimer/VEGFA homodimer	0.024	0.042	-10000	0	-0.3	8	8
RHOA	0.026	0.061	-10000	0	-0.42	9	9
S1P/S1P3/Gq	-0.006	0.079	-10000	0	-0.23	49	49
GNAQ	0	0	-10000	0	-10000	0	0
GNAZ	0.024	0.07	-10000	0	-0.42	12	12
G12/G13	0.044	0.033	-10000	0	-0.3	3	3
GNA14	-0.009	0.13	-10000	0	-0.42	43	43
GNA15	0.03	0.046	-10000	0	-0.42	5	5
GNA12	0.035	0.007	-10000	0	-10000	0	0
GNA13	0.029	0.037	-10000	0	-0.42	3	3
GNA11	0.033	0.036	-10000	0	-0.42	3	3
Rac1/GTP	0.008	0.092	-10000	0	-0.28	22	22

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.03	0.014	-10000	0	-10000	0	0
CDC42/GTP	0.003	0.087	-10000	0	-0.22	41	41
PLCG1	-0.009	0.074	-10000	0	-0.23	38	38
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.028	0.054	-10000	0	-0.42	7	7
GNAI3	0.035	0.006	-10000	0	-10000	0	0
G12/G13	0.044	0.033	-10000	0	-0.3	3	3
cell migration	0.002	0.085	-10000	0	-0.22	41	41
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
MAPK3	-0.006	0.07	-10000	0	-0.22	35	35
MAPK1	-0.005	0.07	-10000	0	-0.22	43	43
S1P/S1P5/Gi	0	0.077	-10000	0	-0.24	40	40
GNAI1	0.017	0.087	-10000	0	-0.42	19	19
CDC42/GDP	0.026	0.006	-10000	0	-10000	0	0
S1P/S1P5/G12	0.024	0.005	-10000	0	-10000	0	0
RHOA	0.033	0.07	0.19	63	-0.24	11	74
S1P/S1P4/Gi	0	0.077	-10000	0	-0.24	40	40
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.023	0.07	-10000	0	-0.42	12	12
S1P/S1P4/G12/G13	0.038	0.027	-10000	0	-0.23	3	3
GNA12	0.035	0.007	-10000	0	-10000	0	0
GNA13	0.029	0.037	-10000	0	-0.42	3	3
CDC42	0.035	0.008	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.015	0.039	-10000	0	-0.25	13	13
ADCY5	-0.013	0.039	-10000	0	-0.25	13	13
ADCY6	-0.012	0.026	-10000	0	-0.25	6	6
ADCY7	-0.009	0.024	-10000	0	-0.25	5	5
ADCY1	-0.011	0.024	-10000	0	-0.25	5	5
ADCY2	-0.029	0.071	-10000	0	-0.26	44	44
ADCY3	-0.014	0.036	-10000	0	-0.25	11	11
ADCY8	-0.008	0.022	-10000	0	-0.25	4	4
PRKCE	0.005	0.033	-10000	0	-0.3	6	6
ADCY9	-0.016	0.045	-10000	0	-0.27	15	15
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	0.021	0.086	0.2	45	-0.26	9	54

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.035	0.021	-10000	0	-0.42	1	1
HDAC2	0.032	0.023	-10000	0	-0.42	1	1
GNB1/GNG2	0.034	0.1	-10000	0	-0.26	53	53
forebrain development	-0.005	0.14	-10000	0	-0.56	18	18
GNAO1	0.03	0.014	-10000	0	-10000	0	0
SMO/beta Arrestin2	0.014	0.1	-10000	0	-0.3	48	48
SMO	-0.01	0.13	-10000	0	-0.42	48	48
ARRB2	0.033	0.011	-10000	0	-10000	0	0
GLI3/SPOP	0.005	0.15	-10000	0	-0.41	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
GSK3B	0.036	0.005	-10000	0	-10000	0	0
GNAI2	0.028	0.054	-10000	0	-0.42	7	7
SIN3/HDAC complex	0.076	0.045	-10000	0	-0.23	5	5
GNAI1	0.017	0.087	-10000	0	-0.42	19	19
XPO1	0.037	0.005	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.02	0.17	-10000	0	-0.56	27	27
SAP30	0.03	0.046	-10000	0	-0.42	5	5
mol:GDP	-0.01	0.13	-10000	0	-0.42	48	48
MIM/GLI2A	0.002	0.11	-10000	0	-0.42	31	31
IFT88	0.021	0.075	-10000	0	-0.42	14	14
GNAI3	0.036	0.006	-10000	0	-10000	0	0
GLI2	0.014	0.079	-10000	0	-0.33	15	15
GLI3	-0.008	0.15	0.24	2	-0.42	30	32
CSNK1D	0.034	0.009	-10000	0	-10000	0	0
CSNK1E	0.034	0.009	-10000	0	-10000	0	0
SAP18	0.034	0.01	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.021	0.075	-10000	0	-0.42	14	14
GNG2	0.034	0.021	-10000	0	-0.42	1	1
Gi family/GTP	-0.017	0.12	-10000	0	-0.3	55	55
SIN3B	0.036	0.005	-10000	0	-10000	0	0
SIN3A	0.035	0.007	-10000	0	-10000	0	0
GLI3/Su(fu)	-0.006	0.14	-10000	0	-0.41	36	36
GLI2/Su(fu)	0.004	0.11	-10000	0	-0.4	16	16
FOXA2	-0.022	0.2	-10000	0	-0.7	35	35
neural tube patterning	-0.005	0.14	-10000	0	-0.56	18	18
SPOP	0.033	0.022	-10000	0	-0.42	1	1
Su(fu)/PIAS1	0.009	0.091	-10000	0	-0.32	16	16
GNB1	0.032	0.045	-10000	0	-0.42	5	5
CSNK1G2	0.033	0.029	-10000	0	-0.42	2	2
CSNK1G3	0.035	0.007	-10000	0	-10000	0	0
MTSS1	0.002	0.11	-10000	0	-0.42	31	31
embryonic limb morphogenesis	-0.005	0.14	-10000	0	-0.56	18	18
SUFU	-0.001	0.084	-10000	0	-0.35	16	16
LGALS3	-0.009	0.14	-10000	0	-0.42	49	49
catabolic process	0.015	0.15	-10000	0	-0.48	21	21
GLI3A/CBP	0.035	0.042	-10000	0	-0.33	6	6
KIF3A	0.029	0.054	-10000	0	-0.42	7	7
GLI1	-0.006	0.14	-10000	0	-0.58	18	18
RAB23	0.03	0.046	-10000	0	-0.42	5	5
CSNK1A1	0.036	0.006	-10000	0	-10000	0	0
IFT172	0.033	0.035	-10000	0	-0.42	3	3
RBBP7	0.034	0.029	-10000	0	-0.42	2	2
Su(fu)/Galectin3	-0.014	0.12	-10000	0	-0.34	40	40
GNAZ	0.023	0.07	-10000	0	-0.42	12	12
RBBP4	0.035	0.021	-10000	0	-0.42	1	1
CSNK1G1	0.035	0.007	-10000	0	-10000	0	0
PIAS1	0.035	0.007	-10000	0	-10000	0	0
PRKACA	0.036	0.005	-10000	0	-10000	0	0
GLI2/SPOP	0.028	0.082	-10000	0	-0.32	14	14
STK36	0.021	0.082	-10000	0	-0.42	17	17
Gi family/GNB1/GNG2/GDP	-0.021	0.12	-10000	0	-0.38	37	37
PTCH1	-0.004	0.13	-10000	0	-0.51	18	18
MIM/GLI1	-0.001	0.14	-10000	0	-0.53	17	17
CREBBP	0.035	0.042	-10000	0	-0.33	6	6
Su(fu)/SIN3/HDAC complex	0.009	0.097	-10000	0	-0.42	16	16

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.045	0.048	-10000	0	-0.3	9	9
FBXW11	0.033	0.029	-10000	0	-0.42	2	2
NF kappa B1 p50/c-Rel	0.026	0.039	-10000	0	-0.25	8	8
NF kappa B1 p50/RelA/I kappa B alpha	0.003	0.1	0.2	1	-0.35	19	20
NFKBIA	-0.016	0.1	-10000	0	-0.24	75	75
MAPK14	0.036	0.005	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.029	0.024	-10000	0	-0.24	2	2
ARRB2	0.017	0.006	-10000	0	-10000	0	0
REL	0.025	0.07	-10000	0	-0.42	12	12
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.026	0.039	-10000	0	-0.25	8	8
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.031	0.017	-10000	0	-10000	0	0
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
NF kappa B1 p50 dimer	0.023	0.021	0.26	3	-10000	0	3
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
NFKB1	0.014	0.007	-10000	0	-10000	0	0
RELA	0.035	0.006	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	-0.004	0.1	-10000	0	-0.25	52	52
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.003	0.1	-10000	0	-0.35	20	20
SRC	0.033	0.029	-10000	0	-0.42	2	2
PI3K	0.036	0.065	-10000	0	-0.3	17	17
NF kappa B1 p50/RelA	-0.003	0.099	-10000	0	-0.25	50	50
IKBKB	0.03	0.014	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.033	0.029	-10000	0	-0.42	2	2
SYK	0.005	0.11	-10000	0	-0.42	34	34
I kappa B alpha/PIK3R1	-0.008	0.12	-10000	0	-0.35	29	29
cell death	0.003	0.099	-10000	0	-0.33	20	20
NF kappa B1 p105/c-Rel	0.026	0.039	-10000	0	-0.25	8	8
LCK	-0.017	0.14	-10000	0	-0.42	54	54
BCL3	0.027	0.061	-10000	0	-0.42	9	9

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.036	0.071	-10000	0	-0.31	19	19
AKT1	0.011	0.12	0.32	1	-0.39	21	22
PTK2B	0	0.089	0.36	1	-0.48	8	9
VEGFR2 homodimer/Frs2	0.029	0.078	-10000	0	-0.38	13	13
CAV1	0.027	0.054	-10000	0	-0.42	7	7
CALM1	0.035	0.007	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.027	0.082	-10000	0	-0.37	13	13
endothelial cell proliferation	0.034	0.12	0.32	10	-0.44	8	18
mol:Ca2+	0.005	0.097	-10000	0	-0.46	10	10
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.045	0.085	-10000	0	-0.43	9	9
RP11-342D11.1	-0.01	0.096	-10000	0	-0.3	34	34
CDH5	0.027	0.037	-10000	0	-0.42	3	3
VEGFA homodimer	0.037	0.087	-10000	0	-0.23	44	44
SHC1	0.028	0.025	-10000	0	-0.42	1	1
SHC2	-0.025	0.15	-10000	0	-0.42	66	66
HRAS/GDP	0.02	0.09	-10000	0	-0.41	9	9
SH2D2A	-0.001	0.11	-10000	0	-0.42	30	30
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.035	0.11	-10000	0	-0.44	13	13
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.005	0.1	-10000	0	-0.28	40	40
VEGFR1 homodimer	0.026	0.057	-10000	0	-0.42	8	8
SHC/GRB2/SOS1	0.043	0.1	-10000	0	-0.44	9	9
GRB10	-0.003	0.12	-10000	0	-0.5	20	20
PTPN11	0.036	0.004	-10000	0	-10000	0	0
GRB2	0.033	0.011	-10000	0	-10000	0	0
PAK1	0.015	0.085	-10000	0	-0.42	18	18
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.042	0.1	-10000	0	-0.44	11	11
HRAS	0.032	0.036	-10000	0	-0.42	3	3
VEGF/Rho/ROCK1/Integrin Complex	0.004	0.1	-10000	0	-0.34	25	25
HIF1A	-0.007	0.13	-10000	0	-0.42	46	46
FRS2	0.033	0.022	-10000	0	-0.42	1	1
oxygen and reactive oxygen species metabolic process	0.043	0.084	-10000	0	-0.36	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.035	0.006	-10000	0	-10000	0	0
Nck/Pak	0.032	0.068	-10000	0	-0.3	19	19
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.021	0.095	-10000	0	-0.38	17	17
mol:GDP	0.031	0.096	-10000	0	-0.43	9	9
mol:NADP	0.019	0.1	-10000	0	-0.4	12	12
eNOS/Hsp90	0.017	0.097	-10000	0	-0.38	12	12
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
mol:IP3	0.004	0.098	-10000	0	-0.47	10	10
HIF1A/ARNT	0.02	0.1	-10000	0	-0.3	44	44
SHB	0.031	0.046	-10000	0	-0.42	5	5
VEGFA	-0.001	0.015	-10000	0	-10000	0	0
VEGFC	0.022	0.075	-10000	0	-0.42	14	14
FAK1/Vinculin	0.015	0.12	0.34	2	-0.45	13	15
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.026	0.061	-10000	0	-0.42	9	9
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.034	0.1	-10000	0	-0.29	29	29
PTPN6	0.032	0.03	-10000	0	-0.42	2	2
EPAS1	0.028	0.077	-10000	0	-0.4	14	14
mol:L-citrulline	0.019	0.1	-10000	0	-0.4	12	12
ITGAV	0.022	0.078	-10000	0	-0.42	15	15
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.042	0.081	-10000	0	-0.34	13	13
VEGFR2 homodimer/VEGFA homodimer	0.023	0.11	-10000	0	-0.33	35	35
VEGFR2/3 heterodimer	0.03	0.078	-10000	0	-0.38	13	13
VEGFB	0.034	0.021	-10000	0	-0.42	1	1
MAPK11	-0.014	0.11	0.26	2	-0.44	16	18
VEGFR2 homodimer	0.012	0.084	-10000	0	-0.44	13	13
FLT1	0.026	0.058	-10000	0	-0.42	8	8
NEDD4	0.021	0.071	-10000	0	-0.42	11	11
MAPK3	0.003	0.095	0.27	7	-0.4	9	16
MAPK1	-0.002	0.095	0.25	6	-0.41	10	16
VEGFA145/NRP2	0.023	0.023	-10000	0	-0.32	1	1
VEGFR1/2 heterodimer	0.024	0.089	-10000	0	-0.37	18	18
KDR	0.012	0.084	-10000	0	-0.44	13	13
VEGFA165/NRP1/VEGFR2 homodimer	0.024	0.11	-10000	0	-0.31	33	33
SRC	0.033	0.029	-10000	0	-0.42	2	2
platelet activating factor biosynthetic process	0.003	0.099	0.27	5	-0.41	10	15
PI3K	0.005	0.13	-10000	0	-0.49	15	15
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.027	0.083	-10000	0	-0.37	14	14
FES	0.001	0.11	-10000	0	-0.33	31	31
GAB1	0.016	0.12	-10000	0	-0.4	25	25
VEGFR2 homodimer/VEGFA homodimer/Src	0.027	0.081	-10000	0	-0.34	15	15
CTNNB1	0.025	0.067	-10000	0	-0.42	11	11
SOS1	0.035	0.021	-10000	0	-0.42	1	1
ARNT	0.035	0.006	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.031	0.11	-10000	0	-0.41	13	13
VEGFR2 homodimer/VEGFA homodimer/Yes	0.023	0.088	-10000	0	-0.34	19	19
PI3K/GAB1	0.02	0.14	0.28	1	-0.41	23	24
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.042	0.098	-10000	0	-0.39	9	9
PRKACA	0.036	0.005	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.04	0.099	-10000	0	-0.38	18	18
HSP90AA1	0	0	-10000	0	-10000	0	0
CDC42	0.004	0.1	-10000	0	-0.32	31	31
actin cytoskeleton reorganization	0.004	0.1	-10000	0	-0.28	40	40
PTK2	-0.006	0.1	-10000	0	-0.51	12	12
EDG1	-0.006	0.14	-10000	0	-0.52	27	27
mol:DAG	0.004	0.098	-10000	0	-0.47	10	10
CaM/Ca2+	0.021	0.096	-10000	0	-0.45	9	9
MAP2K3	-0.011	0.098	-10000	0	-0.45	12	12
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.016	0.13	-10000	0	-0.51	20	20
PLCG1	0.004	0.099	-10000	0	-0.47	10	10
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.04	0.088	-10000	0	-0.39	10	10
IQGAP1	0.035	0.008	-10000	0	-10000	0	0
YES1	0.029	0.05	-10000	0	-0.42	6	6
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.028	0.083	-10000	0	-0.38	13	13
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.027	0.082	-10000	0	-0.38	13	13
cell migration	0.017	0.1	0.3	3	-0.47	9	12
mol:PI-3-4-5-P3	0.006	0.12	-10000	0	-0.44	16	16
FYN	0.027	0.054	-10000	0	-0.42	7	7
VEGFB/NRP1	0.009	0.1	-10000	0	-0.3	34	34
mol:NO	0.019	0.1	-10000	0	-0.4	12	12
PXN	0.036	0.004	-10000	0	-10000	0	0
HRAS/GTP	0.004	0.082	-10000	0	-0.41	9	9
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.005	0.13	-10000	0	-0.51	20	20
VHL	0.035	0.007	-10000	0	-10000	0	0
ITGB3	0.029	0.046	-10000	0	-0.42	5	5
NOS3	0.018	0.11	-10000	0	-0.46	12	12
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.005	0.12	-10000	0	-0.26	73	73
RAC1	0.035	0.006	-10000	0	-10000	0	0
PRKCA	-0.006	0.084	-10000	0	-0.47	7	7
PRKCB	-0.009	0.089	-10000	0	-0.44	10	10
VCL	0.035	0.021	-10000	0	-0.42	1	1
VEGFA165/NRP1	-0.007	0.095	-10000	0	-0.3	34	34
VEGFR1/2 heterodimer/VEGFA homodimer	0.021	0.092	-10000	0	-0.36	18	18
VEGFA165/NRP2	0.023	0.023	-10000	0	-0.32	1	1
MAPKKK cascade	0.032	0.12	0.34	3	-0.44	16	19
NRP2	0.034	0.021	-10000	0	-0.42	1	1
VEGFC homodimer	0.022	0.075	-10000	0	-0.42	14	14
NCK1	0.034	0.021	-10000	0	-0.42	1	1
ROCK1	0.036	0.006	-10000	0	-10000	0	0
FAK1/Paxillin	0.015	0.12	0.34	2	-0.46	13	15
MAP3K13	0.001	0.11	-10000	0	-0.47	12	12
PDPK1	-0.002	0.1	0.26	2	-0.39	15	17

×

Regulation of Androgen receptor activity

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
HDAC1	0.016	0.015	-10000	0	-0.3	1	1
SMARCC1	0.003	0.12	-10000	0	-1.1	5	5
REL	0.024	0.07	-10000	0	-0.42	12	12
HDAC7	-0.036	0.1	0.21	2	-0.31	39	41
JUN	-0.001	0.12	-10000	0	-0.42	39	39
EP300	0.032	0.03	-10000	0	-0.42	2	2
KAT2B	0	0	-10000	0	-10000	0	0
KAT5	0	0	-10000	0	-10000	0	0
MAPK14	0	0.058	-10000	0	-0.31	15	15
FOXO1	0	0	-10000	0	-10000	0	0
T-DHT/AR	-0.007	0.13	0.27	1	-0.32	40	41
MAP2K6	0.011	0.08	-10000	0	-0.43	15	15
BRM/BAF57	0.048	0.024	-10000	0	-0.3	1	1
MAP2K4	0.023	0.031	-10000	0	-0.42	1	1
SMARCA2	0.034	0.022	-10000	0	-0.42	1	1
PDE9A	-0.001	0.12	-10000	0	-0.99	5	5
NCOA2	0.025	0.047	-10000	0	-0.42	5	5
CEBPA	0.024	0.07	-10000	0	-0.42	12	12
EHMT2	0.036	0.005	-10000	0	-10000	0	0
cell proliferation	0.027	0.13	0.31	18	-0.35	13	31
NR0B1	0.03	0.036	-10000	0	-0.42	3	3
EGR1	-0.037	0.16	-10000	0	-0.42	76	76
RXRs/9cRA	0.048	0.051	-10000	0	-0.23	11	11
AR/RACK1/Src	0.003	0.1	0.29	4	-0.3	15	19
AR/GR	-0.026	0.12	0.23	2	-0.23	100	102
GNB2L1	0.034	0.035	-10000	0	-0.42	3	3
PKN1	0.033	0.035	-10000	0	-0.42	3	3
RCHY1	0.022	0.075	-10000	0	-0.42	14	14
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0.033	-10000	0	-0.31	3	3
T-DHT/AR/TIF2/CARM1	0.01	0.092	0.36	1	-0.3	11	12
SRC	-0.01	0.074	0.19	37	-0.25	17	54
NR3C1	0.024	0.072	-10000	0	-0.42	13	13
KLK3	-0.016	0.093	-10000	0	-10000	0	0
APPBP2	0.025	0.024	-10000	0	-10000	0	0
TRIM24	0.036	0.008	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.032	0.07	0.15	1	-0.27	23	24
TMPRSS2	-0.14	0.38	-10000	0	-0.95	87	87
RXRG	0.022	0.055	-10000	0	-0.42	7	7
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	0.034	0.029	-10000	0	-0.42	2	2
RXRB	0.034	0.029	-10000	0	-0.42	2	2
CARM1	0.035	0.021	-10000	0	-0.42	1	1
NR2C2	0.035	0.008	-10000	0	-10000	0	0
KLK2	0.011	0.075	0.31	3	-0.3	3	6
AR	-0.032	0.11	0.19	1	-0.24	92	93
SENP1	0.036	0.006	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
MDM2	0.033	0.008	-10000	0	-10000	0	0
SRY	0.024	0.07	-10000	0	-0.42	12	12
GATA2	0.029	0.046	-10000	0	-0.42	5	5
MYST2	0.032	0.03	-10000	0	-0.42	2	2
HOXB13	0.024	0.018	-10000	0	-10000	0	0
T-DHT/AR/RACK1/Src	-0.001	0.1	0.29	5	-0.31	15	20
positive regulation of transcription	0.029	0.046	-10000	0	-0.42	5	5
DNAJA1	0.024	0.042	-10000	0	-0.42	3	3
proteasomal ubiquitin-dependent protein catabolic process	0.013	0.052	-10000	0	-0.3	13	13
NCOA1	0.036	0.054	-10000	0	-0.33	9	9
SPDEF	-0.044	0.18	-10000	0	-0.42	90	90
T-DHT/AR/TIF2	0.014	0.078	0.24	8	-0.3	6	14
T-DHT/AR/Hsp90	-0.032	0.07	0.15	1	-0.27	23	24
GSK3B	0.036	0.005	-10000	0	-10000	0	0
NR2C1	0.03	0.05	-10000	0	-0.42	6	6
mol:T-DHT	-0.008	0.072	0.21	30	-0.26	14	44
SIRT1	0.036	0.006	-10000	0	-10000	0	0
ZMIZ2	-0.001	0	-10000	0	-10000	0	0
POU2F1	0.017	0.055	-10000	0	-0.18	2	2
T-DHT/AR/DAX-1	-0.007	0.098	0.27	3	-0.29	22	25
CREBBP	0.033	0.011	-10000	0	-10000	0	0
SMARCE1	0.034	0.01	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.035	0.007	-9999	-10000	0	0
SPHK1	0.005	0.11	-9999	-0.42	30	30
GNAI2	0.028	0.054	-9999	-0.42	7	7
mol:S1P	0.002	0.065	-9999	-0.27	25	25
GNAO1	0.03	0.014	-9999	-10000	0	0
mol:Sphinganine-1-P	-0.003	0.074	-9999	-0.3	29	29
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.041	0.07	-9999	-0.22	23	23
GNAI3	0.035	0.006	-9999	-10000	0	0
G12/G13	0.044	0.033	-9999	-0.3	3	3
S1PR3	0	0	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	0.013	0.095	-9999	-0.42	23	23
S1P1/S1P	0.024	0.088	-9999	-0.25	37	37
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
GNAI1	0.017	0.087	-9999	-0.42	19	19
S1P/S1P5/G12	0.029	0.066	-9999	-0.22	24	24
S1P/S1P3/Gq	-0.001	0.095	-9999	-0.25	51	51
S1P/S1P4/Gi	0.002	0.094	-9999	-0.26	42	42
GNAQ	0	0	-9999	-10000	0	0
GNAZ	0.023	0.07	-9999	-0.42	12	12
GNA14	-0.009	0.13	-9999	-0.42	43	43
GNA15	0.03	0.046	-9999	-0.42	5	5
GNA12	0.035	0.007	-9999	-10000	0	0
GNA13	0.029	0.037	-9999	-0.42	3	3
GNA11	0.033	0.036	-9999	-0.42	3	3
ABCC1	0.029	0.042	-9999	-0.42	4	4

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.001	0.09	0.22	50	-10000	0	50
GNAI2	0.028	0.054	-10000	0	-0.42	7	7
S1P/S1P5/G12	0.024	0.005	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.03	0.014	-10000	0	-10000	0	0
RhoA/GTP	-0.001	0.092	-10000	0	-0.22	50	50
negative regulation of cAMP metabolic process	0	0.076	-10000	0	-0.24	40	40
GNAZ	0.023	0.07	-10000	0	-0.42	12	12
GNAI3	0.035	0.006	-10000	0	-10000	0	0
GNA12	0.035	0.007	-10000	0	-10000	0	0
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0	0.077	-10000	0	-0.24	40	40
RhoA/GDP	0.02	0.043	-10000	0	-0.3	9	9
RHOA	0.026	0.061	-10000	0	-0.42	9	9
GNAI1	0.017	0.087	-10000	0	-0.42	19	19

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.035	0.021	-10000	0	-0.42	1	1
HDAC3	0.036	0.006	-10000	0	-10000	0	0
VDR	0.02	0.082	-10000	0	-0.42	17	17
Cbp/p300/PCAF	0.041	0.026	-10000	0	-0.24	2	2
EP300	0.032	0.03	-10000	0	-0.42	2	2
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.014	0.057	0.19	1	-0.31	4	5
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.036	0.005	-10000	0	-10000	0	0
AKT1	0.028	0.092	0.21	55	-0.3	5	60
RAR alpha/9cRA/Cyclin H	0.045	0.1	0.26	1	-0.32	8	9
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.018	0.065	-10000	0	-0.28	8	8
CDC2	0.01	0.094	-10000	0	-0.42	22	22
response to UV	-0.002	0.008	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.031	0.06	-10000	0	-0.25	11	11
NCOR2	0.036	0.005	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.015	0.058	-10000	0	-0.3	17	17
RXRs/RARs/NRIP1/9cRA	-0.003	0.19	0.31	1	-0.53	52	53
NCOA2	0.025	0.047	-10000	0	-0.42	5	5
NCOA3	0.032	0.03	-10000	0	-0.42	2	2
NCOA1	0.031	0.045	-10000	0	-0.42	5	5
VDR/VDR/DNA	0.02	0.082	-10000	0	-0.42	17	17
RARG	0.031	0.018	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.047	0.01	-10000	0	-10000	0	0
MAPK3	0.027	0.029	-10000	0	-0.42	1	1
MAPK1	0.033	0.022	-10000	0	-0.42	1	1
MAPK8	0.027	0.041	-10000	0	-0.42	3	3
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.027	0.13	-10000	0	-0.34	34	34
RARA	0.011	0.044	-10000	0	-0.23	10	10
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.015	0.055	-10000	0	-0.33	3	3
PRKCA	0.024	0.032	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.008	0.2	-10000	0	-0.57	52	52
RXRG	0.011	0.045	-10000	0	-0.3	6	6
RXRA	0.017	0.09	-10000	0	-0.32	8	8
RXRB	0.017	0.037	-10000	0	-0.28	2	2
VDR/Vit D3/DNA	0.015	0.058	-10000	0	-0.3	17	17
RBP1	-0.028	0.15	-10000	0	-0.42	67	67
CRBP1/9-cic-RA	-0.018	0.11	-10000	0	-0.3	67	67
RARB	0.011	0.09	-10000	0	-0.42	20	20
PRKCG	0.029	0.032	-10000	0	-10000	0	0
MNAT1	0.035	0.007	-10000	0	-10000	0	0
RAR alpha/RXRs	0.004	0.14	0.42	1	-0.37	34	35
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.03	0.11	0.27	1	-0.36	11	12
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.074	0.23	1	-0.29	6	7
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.008	0.2	-10000	0	-0.58	52	52
positive regulation of DNA binding	0.033	0.095	-10000	0	-0.3	9	9
NRIP1	-0.071	0.38	-10000	0	-1.2	51	51
RXRs/RARs	0.011	0.16	-10000	0	-0.41	52	52
RXRs/RXRs/DNA/9cRA	-0.008	0.11	-10000	0	-0.32	34	34
PRKACA	0.036	0.005	-10000	0	-10000	0	0
CDK7	0.034	0.008	-10000	0	-10000	0	0
TFIIH	0.068	0.024	-10000	0	-0.24	1	1
RAR alpha/9cRA	0.066	0.066	-10000	0	-0.22	4	4
CCNH	0.034	0.022	-10000	0	-0.42	1	1
CREBBP	0.033	0.011	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.065	0.028	-10000	0	-0.2	1	1

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	0.014	0.097	-10000	0	-1	4	4
MKNK1	0.035	0.006	-10000	0	-10000	0	0
MAPK14	0.031	0.049	-10000	0	-0.3	4	4
ATF2/c-Jun	-0.022	0.16	-10000	0	-0.54	40	40
MAPK11	0.03	0.048	-10000	0	-0.3	4	4
MITF	0.02	0.053	-10000	0	-0.34	7	7
MAPKAPK5	0.023	0.043	-10000	0	-0.33	4	4
KRT8	0.011	0.073	-10000	0	-0.28	24	24
MAPKAPK3	0.035	0.008	-10000	0	-10000	0	0
MAPKAPK2	0.025	0.043	-10000	0	-0.42	4	4
p38alpha-beta/CK2	0.041	0.065	-10000	0	-0.43	4	4
CEBPB	0.019	0.054	-10000	0	-0.32	9	9
SLC9A1	0.023	0.043	-10000	0	-0.33	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.017	0.07	0.23	1	-0.31	8	9
p38alpha-beta/MNK1	0.056	0.06	-10000	0	-0.36	3	3
JUN	-0.025	0.16	-10000	0	-0.54	40	40
PPARGC1A	0.016	0.068	-10000	0	-0.34	13	13
USF1	0.013	0.057	-10000	0	-0.29	13	13
RAB5/GDP/GDI1	0.024	0.053	-10000	0	-0.23	5	5
NOS2	0.016	0.042	-10000	0	-0.34	4	4
DDIT3	0.023	0.045	-10000	0	-0.32	5	5
RAB5A	0.036	0.006	-10000	0	-10000	0	0
HSPB1	-0.012	0.084	0.28	2	-0.26	44	46
p38alpha-beta/HBP1	0.053	0.068	-10000	0	-0.31	7	7
CREB1	0.015	0.061	-10000	0	-0.3	9	9
RAB5/GDP	0.026	0.004	-10000	0	-10000	0	0
EIF4E	0.016	0.045	0.24	2	-0.32	3	5
RPS6KA4	0.022	0.048	-10000	0	-0.36	5	5
PLA2G4A	0.001	0.064	-10000	0	-0.28	20	20
GDI1	0.023	0.045	-10000	0	-0.32	5	5
TP53	0	0.061	-10000	0	-0.33	9	9
RPS6KA5	0.009	0.075	-10000	0	-0.28	27	27
ESR1	-0.055	0.14	-10000	0	-0.28	129	129
HBP1	0.033	0.036	-10000	0	-0.42	3	3
MEF2C	0.01	0.08	-10000	0	-0.32	24	24
MEF2A	0.022	0.045	-10000	0	-0.32	5	5
EIF4EBP1	0.01	0.066	-10000	0	-0.31	12	12
KRT19	-0.002	0.09	-10000	0	-0.28	42	42
ELK4	0.018	0.041	-10000	0	-0.31	4	4
ATF6	0.018	0.044	-10000	0	-0.32	5	5
ATF1	0.016	0.062	-10000	0	-0.3	9	9
p38alpha-beta/MAPKAPK2	0.042	0.069	-10000	0	-0.35	6	6
p38alpha-beta/MAPKAPK3	0.054	0.063	-10000	0	-0.35	4	4

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.041	0.019	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.035	0.007	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.018	0.078	-10000	0	-0.42	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.029	0.024	-10000	0	-0.42	1	1
RAC1-CDC42/GTP/PAK family	0.002	0.065	-10000	0	-0.21	39	39
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.029	0.05	-10000	0	-0.42	6	6
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.031	0.013	-10000	0	-10000	0	0
FYN	0.027	0.054	-10000	0	-0.42	7	7
MAP3K12	0.036	0.004	-10000	0	-10000	0	0
FGR	0.035	0.008	-10000	0	-10000	0	0
p38 alpha/TAB1	-0.005	0.14	0.22	2	-0.34	49	51
PRKG1	0.035	0.006	-10000	0	-10000	0	0
DUSP8	0.02	0.08	-10000	0	-0.42	16	16
PGK/cGMP/p38 alpha	-0.009	0.14	0.21	1	-0.34	47	48
apoptosis	-0.005	0.14	0.21	2	-0.33	50	52
RAL/GTP	0.045	0.028	-10000	0	-0.25	4	4
LYN	0.03	0.014	-10000	0	-10000	0	0
DUSP1	0.003	0.11	-10000	0	-0.42	34	34
PAK1	0.015	0.085	-10000	0	-0.42	18	18
SRC	0.033	0.029	-10000	0	-0.42	2	2
RAC1/OSM/MEKK3/MKK3	0.073	0.041	-10000	0	-0.23	1	1
TRAF6	0.035	0.021	-10000	0	-0.42	1	1
RAC1	0.035	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	0.035	0.006	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.046	0.013	-10000	0	-10000	0	0
MAPK11	-0.014	0.14	0.24	3	-0.4	37	40
BLK	0.022	0.038	-10000	0	-0.42	3	3
HCK	0.018	0.087	-10000	0	-0.42	19	19
MAP2K3	0.032	0.023	-10000	0	-0.42	1	1
DUSP16	0.03	0.046	-10000	0	-0.42	5	5
DUSP10	0.013	0.082	-10000	0	-0.42	17	17
TRAF6/MEKK3	0.039	0.021	-10000	0	-0.23	1	1
MAP3K7IP1	0.034	0.009	-10000	0	-10000	0	0
MAPK14	-0.018	0.14	0.21	5	-0.35	56	61
positive regulation of innate immune response	-0.018	0.17	0.27	3	-0.42	47	50
LCK	-0.017	0.14	-10000	0	-0.42	54	54
p38alpha-beta/MKP7	-0.007	0.17	0.28	3	-0.41	45	48
p38alpha-beta/MKP5	-0.013	0.16	0.29	2	-0.42	42	44
PGK/cGMP	0.026	0.004	-10000	0	-10000	0	0
PAK2	0.036	0	-10000	0	-10000	0	0
p38alpha-beta/MKP1	-0.018	0.17	0.28	3	-0.42	48	51
CDC42	0.035	0.008	-10000	0	-10000	0	0
RALB	0.032	0.041	-10000	0	-0.42	4	4
RALA	0.035	0.007	-10000	0	-10000	0	0
PAK3	0.016	0.085	-10000	0	-0.42	18	18

×

Glypican 2 network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.018	0.085	-9999	-0.42	18	18
GPC2	0	0	-9999	-10000	0	0
GPC2/Midkine	0.014	0.06	-9999	-0.3	18	18
neuron projection morphogenesis	0.014	0.06	-9999	-0.3	18	18

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.032	0.013	-9999	-10000	0	0
ELF1	0.014	0.096	-9999	-0.34	33	33
CCNA2	0.009	0.1	-9999	-0.42	28	28
PIK3CA	0.034	0.022	-9999	-0.42	1	1
JAK3	0.036	0.005	-9999	-10000	0	0
PIK3R1	0.02	0.08	-9999	-0.42	16	16
JAK1	0.033	0.036	-9999	-0.42	3	3
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.022	0.14	-9999	-0.4	25	25
SHC1	0.028	0.025	-9999	-0.42	1	1
SP1	0.032	0.073	-9999	-0.37	15	15
IL2RA	-0.024	0.17	-9999	-0.61	36	36
IL2RB	0.012	0.097	-9999	-0.42	24	24
SOS1	0.035	0.021	-9999	-0.42	1	1
IL2RG	0.031	0.041	-9999	-0.42	4	4
G1/S transition of mitotic cell cycle	-0.02	0.19	-9999	-0.71	24	24
PTPN11	0.037	0.004	-9999	-10000	0	0
CCND2	0.005	0.11	-9999	-0.68	13	13
LCK	-0.017	0.14	-9999	-0.42	54	54
GRB2	0.034	0.011	-9999	-10000	0	0
IL2	0.033	0.036	-9999	-0.42	3	3
CDK6	0.025	0.058	-9999	-0.42	8	8
CCND3	0.025	0.13	-9999	-0.48	2	2

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.031	0.041	-10000	0	-0.42	4	4
RAS family/GTP/Tiam1	0.011	0.068	-10000	0	-0.28	19	19
NT3 (dimer)/TRKC	0.039	0.046	-10000	0	-0.3	8	8
NT3 (dimer)/TRKB	0.046	0.071	-10000	0	-0.26	22	22
SHC/Grb2/SOS1/GAB1/PI3K	0.016	0.05	-10000	0	-0.21	17	17
RAPGEF1	0.036	0.004	-10000	0	-10000	0	0
BDNF	0.031	0.024	-10000	0	-0.42	1	1
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
DYNLT1	0.034	0.01	-10000	0	-10000	0	0
NTRK1	0.026	0.032	-10000	0	-0.42	2	2
NTRK2	0.02	0.078	-10000	0	-0.42	15	15
NTRK3	0.031	0.013	-10000	0	-10000	0	0
NT-4/5 (dimer)/TRKB	0.033	0.055	-10000	0	-0.25	17	17
neuron apoptosis	0.002	0.14	0.31	53	-0.28	2	55
SHC 2-3/Grb2	-0.003	0.15	0.29	2	-0.34	53	55
SHC1	0.028	0.025	-10000	0	-0.42	1	1
SHC2	-0.036	0.18	0.24	1	-0.44	75	76
SHC3	0.018	0.11	0.25	3	-0.43	18	21
STAT3 (dimer)	-0.016	0.13	-10000	0	-0.34	69	69
NT3 (dimer)/TRKA	0.042	0.055	-10000	0	-0.25	11	11
RIN/GDP	0.068	0.084	0.24	26	-0.25	7	33
GIPC1	0.033	0.035	-10000	0	-0.42	3	3
KRAS	0.028	0.054	-10000	0	-0.42	7	7
DNAJA3	0.007	0.057	0.21	18	-0.28	4	22
RIN/GTP	0.025	0.021	-10000	0	-0.3	2	2
CCND1	-0.077	0.24	-10000	0	-0.69	67	67
MAGED1	0.015	0.095	-10000	0	-0.42	23	23
PTPN11	0.036	0.004	-10000	0	-10000	0	0
RICS	0.023	0.061	-10000	0	-0.42	9	9
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.052	0.036	-10000	0	-0.26	1	1
GRB2	0.033	0.011	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.033	0.033	-10000	0	-0.25	4	4
TRKA/NEDD4-2	0.021	0.08	-10000	0	-0.3	27	27
ELMO1	0.035	0.006	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0.041	0.039	-10000	0	-0.25	8	8
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.032	0.036	-10000	0	-0.42	3	3
DOCK1	0.028	0.057	-10000	0	-0.42	8	8
GAB2	0.031	0.013	-10000	0	-10000	0	0
RIT2	0.033	0.029	-10000	0	-0.42	2	2
RIT1	0.027	0.032	-10000	0	-0.42	2	2
FRS2	0.033	0.022	-10000	0	-0.42	1	1
DNM1	0.033	0.035	-10000	0	-0.42	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.032	0.023	-10000	0	-0.42	1	1
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.043	0.068	0.23	21	-0.25	5	26
mol:GDP	0.071	0.11	0.29	26	-0.36	8	34
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.026	0.005	-10000	0	-10000	0	0
RIT1/GDP	0.041	0.071	0.24	8	-0.24	7	15
TIAM1	0.028	0.057	-10000	0	-0.42	8	8
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
BDNF (dimer)/TRKB	0.052	0.064	-10000	0	-0.25	19	19
KIDINS220/CRKL/C3G	0.047	0.034	-10000	0	-0.3	4	4
SHC/RasGAP	0.037	0.044	-10000	0	-0.3	6	6
FRS2 family/SHP2	0.067	0.025	-10000	0	-0.26	1	1
SHC/GRB2/SOS1/GAB1	0.061	0.054	-10000	0	-0.23	6	6
RIT1/GTP	0.02	0.023	-10000	0	-0.3	2	2
NT3 (dimer)	0.023	0.058	-10000	0	-0.42	8	8
RAP1/GDP	0.048	0.067	0.18	17	-0.23	6	23
KIDINS220/CRKL	0.031	0.041	-10000	0	-0.42	4	4
BDNF (dimer)	0.031	0.024	-10000	0	-0.42	1	1
ubiquitin-dependent protein catabolic process	0.02	0.068	-10000	0	-0.25	27	27
Schwann cell development	-0.007	0.013	-10000	0	-10000	0	0
EHD4	0.031	0.041	-10000	0	-0.42	4	4
FRS2 family/GRB2/SOS1	0.077	0.041	-10000	0	-0.44	1	1
FRS2 family/SHP2/CRK family/C3G/GAB2	0.025	0.06	-10000	0	-0.32	2	2
RAP1B	0.033	0.03	-10000	0	-0.42	2	2
RAP1A	0.031	0.045	-10000	0	-0.42	5	5
CDC42/GTP	0.043	0.07	-10000	0	-0.21	27	27
ABL1	0.036	0.005	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.048	0.023	-10000	0	-0.3	1	1
Rap1/GTP	0.023	0.092	-10000	0	-0.38	11	11
STAT3	-0.016	0.13	-10000	0	-0.34	69	69
axon guidance	0.026	0.061	-10000	0	-0.21	27	27
MAPK3	0.05	0.077	0.19	101	-0.23	5	106
MAPK1	0.051	0.077	0.19	103	-0.23	5	108
CDC42/GDP	0.069	0.085	0.24	29	-0.26	6	35
NTF3	0.023	0.058	-10000	0	-0.42	8	8
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.035	0.031	-10000	0	-0.25	3	3
PI3K	0.036	0.065	-10000	0	-0.3	17	17
FRS3	0.035	0.007	-10000	0	-10000	0	0
FAIM	0.035	0.021	-10000	0	-0.42	1	1
GAB1	0.027	0.061	-10000	0	-0.42	9	9
RASGRF1	0.008	0.062	0.22	19	-0.24	7	26
SOS1	0.035	0.021	-10000	0	-0.42	1	1
MCF2L	0.013	0.037	-10000	0	-0.25	9	9
RGS19	0.031	0.031	-10000	0	-0.42	2	2
CDC42	0.035	0.008	-10000	0	-10000	0	0
RAS family/GTP	0.068	0.098	0.32	3	-0.37	9	12
Rac1/GDP	0.068	0.086	0.24	28	-0.25	7	35
NGF (dimer)/TRKA/GRIT	0.026	0.047	-10000	0	-0.25	11	11
neuron projection morphogenesis	-0.005	0.2	0.44	2	-0.84	18	20
NGF (dimer)/TRKA/NEDD4-2	0.02	0.068	-10000	0	-0.25	27	27
MAP2K1	0.035	0.1	0.36	9	-0.22	6	15
NGFR	0.03	0.036	-10000	0	-0.42	3	3
NGF (dimer)/TRKA/GIPC/GAIP	0.019	0.038	-10000	0	-0.26	7	7
RAS family/GTP/PI3K	0.012	0.065	-10000	0	-0.24	28	28
FRS2 family/SHP2/GRB2/SOS1	0.09	0.047	-10000	0	-0.42	1	1
NRAS	0.029	0.054	-10000	0	-0.42	7	7
GRB2/SOS1	0.048	0.023	-10000	0	-0.3	1	1
PRKCI	0.025	0.064	-10000	0	-0.42	10	10
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.035	0.006	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	0.005	0.061	-10000	0	-0.45	5	5
RASA1	0.029	0.05	-10000	0	-0.42	6	6
TRKA/c-Abl	0.04	0.031	-10000	0	-0.3	2	2
SQSTM1	0.034	0.021	-10000	0	-0.42	1	1
BDNF (dimer)/TRKB/GIPC	0.068	0.065	-10000	0	-0.23	18	18
NGF (dimer)/TRKA/p62/Atypical PKCs	0.041	0.047	-10000	0	-0.22	10	10
MATK	0.031	0.03	-10000	0	-0.42	2	2
NEDD4L	0.007	0.11	-10000	0	-0.42	31	31
RAS family/GDP	-0.012	0.036	-10000	0	-0.17	13	13
NGF (dimer)/TRKA	0.011	0.058	0.23	17	-0.27	5	22
Rac1/GTP	0	0.052	-10000	0	-0.21	15	15
FRS2 family/SHP2/CRK family	0.082	0.055	-10000	0	-0.22	6	6

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.014	0.058	-10000	0	-0.2	27	27
TRAF2/ASK1	0.029	0.066	-10000	0	-0.25	25	25
ATM	0.031	0.013	-10000	0	-10000	0	0
MAP2K3	-0.051	0.16	0.28	2	-0.4	63	65
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.042	0.14	0.29	1	-0.35	55	56
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.027	0.064	-10000	0	-0.42	10	10
TXN	0.009	0.002	-10000	0	-10000	0	0
CALM1	0.035	0.007	-10000	0	-10000	0	0
GADD45A	0.019	0.08	-10000	0	-0.42	16	16
GADD45B	0.025	0.067	-10000	0	-0.42	11	11
MAP3K1	0.01	0.099	-10000	0	-0.42	25	25
MAP3K6	0.034	0.022	-10000	0	-0.42	1	1
MAP3K7	0.033	0.011	-10000	0	-10000	0	0
MAP3K4	0.034	0.01	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.032	0.075	-10000	0	-0.3	24	24
TAK1/TAB family	0.014	0.037	-10000	0	-0.25	7	7
RAC1/OSM/MEKK3	0.058	0.027	-10000	0	-10000	0	0
TRAF2	0.034	0.029	-10000	0	-0.42	2	2
RAC1/OSM/MEKK3/MKK3	-0.019	0.14	-10000	0	-0.32	48	48
TRAF6	0.016	0.024	-10000	0	-0.28	3	3
RAC1	0.035	0.006	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.012	0.13	-10000	0	-0.42	47	47
CCM2	0.035	0.006	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.015	0.086	-10000	0	-0.25	47	47
MAPK11	0.033	0.01	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.018	0.1	-10000	0	-0.23	68	68
OSM/MEKK3	0.045	0.02	-10000	0	-10000	0	0
TAOK1	0.012	0.033	-10000	0	-0.29	6	6
TAOK2	0.015	0.008	-10000	0	-10000	0	0
TAOK3	0.016	0.015	-10000	0	-0.29	1	1
MAP3K7IP1	0.034	0.009	-10000	0	-10000	0	0
MAPK14	0.036	0.005	-10000	0	-10000	0	0
MAP3K7IP2	0.032	0.03	-10000	0	-0.42	2	2
MAP3K5	0.012	0.095	-10000	0	-0.42	23	23
MAP3K10	0.023	0.075	-10000	0	-0.42	14	14
MAP3K3	0.031	0.013	-10000	0	-10000	0	0
TRX/ASK1	0.016	0.06	-10000	0	-0.24	23	23
GADD45/MTK1/MTK1	0.054	0.082	-10000	0	-0.23	33	33

×

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

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
MET/RANBP9	0.046	0.034	-10000	0	-0.3	4	4
CRKL	0.006	0.1	0.3	2	-0.46	15	17
mol:PIP3	0.011	0.054	0.39	9	-10000	0	9
AKT1	0.022	0.078	0.43	4	-10000	0	4
PTK2B	0.028	0.015	-10000	0	-10000	0	0
RAPGEF1	0.004	0.097	0.32	1	-0.44	15	16
RANBP10	0.03	0.014	-10000	0	-10000	0	0
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
HGF/MET/SHIP2	0.054	0.059	-10000	0	-0.26	15	15
MAP3K5	0	0.11	0.27	2	-0.43	17	19
HGF/MET/CIN85/CBL/ENDOPHILINS	0.064	0.073	-10000	0	-0.25	20	20
AP1	-0.022	0.13	-10000	0	-0.3	88	88
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.028	0.025	-10000	0	-0.42	1	1
apoptosis	-0.14	0.34	-10000	0	-0.77	109	109
STAT3 (dimer)	0.01	0.07	-10000	0	-0.31	7	7
GAB1/CRKL/SHP2/PI3K	0.042	0.12	0.34	1	-0.42	16	17
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.024	0.097	-10000	0	-0.43	14	14
PTPN11	0.036	0.004	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.034	0.008	-10000	0	-10000	0	0
PTEN	0.027	0.061	-10000	0	-0.42	9	9
ELK1	-0.001	0.072	0.28	15	-10000	0	15
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.015	0.046	-10000	0	-0.21	5	5
PAK1	0.028	0.099	0.4	10	-10000	0	10
HGF/MET/RANBP10	0.05	0.055	-10000	0	-0.25	12	12
HRAS	0.014	0.1	-10000	0	-0.43	20	20
DOCK1	0.003	0.1	0.31	2	-0.44	15	17
GAB1	0.008	0.1	-10000	0	-0.48	15	15
CRK	0.005	0.098	-10000	0	-0.45	15	15
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.1	-10000	0	-0.42	22	22
JUN	-0.001	0.12	-10000	0	-0.42	39	39
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.007	0.042	-10000	0	-0.2	17	17
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
cell morphogenesis	0.007	0.1	0.28	10	-0.34	9	19
GRB2/SHC	0.034	0.052	-10000	0	-0.19	11	11
FOS	-0.031	0.15	-10000	0	-0.42	66	66
GLMN	0.004	0.001	-10000	0	-10000	0	0
cell motility	-0.001	0.072	0.27	16	-10000	0	16
HGF/MET/MUC20	0.039	0.047	-10000	0	-0.25	12	12
cell migration	0.034	0.051	-10000	0	-0.19	11	11
GRB2	0.033	0.011	-10000	0	-10000	0	0
CBL	0.032	0.012	-10000	0	-10000	0	0
MET/RANBP10	0.039	0.037	-10000	0	-0.29	4	4
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.015	0.054	-10000	0	-0.23	15	15
MET/MUC20	0.022	0.029	-10000	0	-0.3	4	4
RAP1B	0.008	0.099	0.28	7	-0.42	14	21
RAP1A	0.001	0.097	0.31	1	-0.42	17	18
HGF/MET/RANBP9	0.059	0.053	-10000	0	-0.26	12	12
RAF1	0.017	0.1	-10000	0	-0.43	17	17
STAT3	0.009	0.069	-10000	0	-0.31	7	7
cell proliferation	0.042	0.1	0.27	18	-0.32	10	28
RPS6KB1	0.01	0.048	-10000	0	-0.29	10	10
MAPK3	-0.017	0.082	0.68	5	-10000	0	5
MAPK1	0.007	0.15	0.63	27	-10000	0	27
RANBP9	0.035	0.007	-10000	0	-10000	0	0
MAPK8	0.01	0.11	0.29	1	-0.39	19	20
SRC	0.009	0.063	-10000	0	-0.26	6	6
PI3K	0.033	0.074	-10000	0	-0.22	28	28
MET/Glomulin	0.021	0.037	-10000	0	-0.24	5	5
SOS1	0.035	0.021	-10000	0	-0.42	1	1
MAP2K1	0.015	0.096	-10000	0	-0.41	16	16
MET	0.03	0.041	-10000	0	-0.42	4	4
MAP4K1	0.008	0.11	0.31	1	-0.44	16	17
PTK2	0.028	0.016	-10000	0	-10000	0	0
MAP2K2	0.014	0.098	-10000	0	-0.42	16	16
BAD	0.017	0.074	0.42	3	-10000	0	3
MAP2K4	-0.001	0.1	0.26	2	-0.39	17	19
SHP2/GRB2/SOS1/GAB1	0.044	0.098	-10000	0	-0.38	16	16
INPPL1	0.031	0.036	-10000	0	-0.42	3	3
PXN	0.036	0.004	-10000	0	-10000	0	0
SH3KBP1	0.027	0.064	-10000	0	-0.42	10	10
HGS	0	0.04	-10000	0	-0.18	20	20
PLCgamma1/PKC	0.025	0.006	-10000	0	-10000	0	0
HGF	0.028	0.057	-10000	0	-0.42	8	8
RASA1	0.029	0.05	-10000	0	-0.42	6	6
NCK1	0.034	0.021	-10000	0	-0.42	1	1
PTPRJ	0.031	0.046	-10000	0	-0.42	5	5
NCK/PLCgamma1	0.047	0.056	-10000	0	-0.18	21	21
PDPK1	0.027	0.08	0.34	9	-10000	0	9
HGF/MET/SHIP	0.039	0.047	-10000	0	-0.25	12	12

×

FoxO family signaling

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
G6PC	0.041	0.096	-10000	0	-1.3	1	1
PLK1	0.01	0.2	-10000	0	-0.82	11	11
CDKN1B	0.042	0.17	-10000	0	-0.45	31	31
FOXO3	-0.005	0.22	-10000	0	-0.74	20	20
KAT2B	0.001	0.019	-10000	0	-0.043	62	62
FOXO1/SIRT1	0.044	0.054	-10000	0	-0.26	4	4
CAT	-0.008	0.23	-10000	0	-0.91	16	16
CTNNB1	0.025	0.067	-10000	0	-0.42	11	11
AKT1	0.029	0.046	-10000	0	-0.41	2	2
FOXO1	0.026	0.053	0.24	1	-0.28	4	5
MAPK10	0.008	0.06	0.2	9	-0.21	24	33
mol:GTP	0	0.002	-10000	0	-10000	0	0
FOXO4	0.017	0.097	0.28	1	-0.32	18	19
response to oxidative stress	0.004	0.02	-10000	0	-0.053	23	23
FOXO3A/SIRT1	0.021	0.19	-10000	0	-0.59	23	23
XPO1	0.036	0.005	-10000	0	-10000	0	0
EP300	0.034	0.031	-10000	0	-0.42	2	2
BCL2L11	0.029	0.086	-10000	0	-1.2	2	2
FOXO1/SKP2	0.042	0.049	-10000	0	-0.27	3	3
mol:GDP	0.004	0.02	-10000	0	-0.053	23	23
RAN	0.036	0.005	-10000	0	-10000	0	0
GADD45A	0.012	0.22	-10000	0	-0.85	23	23
YWHAQ	0.034	0.029	-10000	0	-0.42	2	2
FOXO1/14-3-3 family	0.038	0.12	-10000	0	-0.4	17	17
MST1	0.028	0.036	-10000	0	-10000	0	0
CSNK1D	0.034	0.009	-10000	0	-10000	0	0
CSNK1E	0.034	0.009	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.009	0.13	-10000	0	-0.4	28	28
YWHAB	0.035	0.008	-10000	0	-10000	0	0
MAPK8	0.018	0.044	0.2	10	-0.21	7	17
MAPK9	0.01	0.058	0.2	8	-0.22	22	30
YWHAG	0.036	0.005	-10000	0	-10000	0	0
YWHAE	0.032	0.012	-10000	0	-10000	0	0
YWHAZ	0.027	0.016	-10000	0	-10000	0	0
SIRT1	0.036	0.02	-10000	0	-10000	0	0
SOD2	0.031	0.16	-10000	0	-0.64	12	12
RBL2	-0.076	0.31	-10000	0	-0.74	74	74
RAL/GDP	0.046	0.037	-10000	0	-0.24	4	4
CHUK	0.019	0.074	-10000	0	-0.42	11	11
Ran/GTP	0.026	0.01	-10000	0	-10000	0	0
CSNK1G2	0.033	0.029	-10000	0	-0.42	2	2
RAL/GTP	0.046	0.038	-10000	0	-0.22	4	4
CSNK1G1	0.035	0.007	-10000	0	-10000	0	0
FASLG	-0.092	0.4	-10000	0	-1.4	45	45
SKP2	0.034	0.009	-10000	0	-10000	0	0
USP7	0.033	0.012	-10000	0	-10000	0	0
IKBKB	0.023	0.035	-10000	0	-10000	0	0
CCNB1	-0.051	0.33	-10000	0	-1.1	38	38
FOXO1-3a-4/beta catenin	0.039	0.16	0.42	1	-0.41	27	28
proteasomal ubiquitin-dependent protein catabolic process	0.042	0.049	-10000	0	-0.27	3	3
CSNK1A1	0.036	0.006	-10000	0	-10000	0	0
SGK1	0.001	0.019	-10000	0	-0.043	62	62
CSNK1G3	0.035	0.007	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.049	0.013	-10000	0	-10000	0	0
ZFAND5	0.018	0.084	0.26	1	-0.28	15	16
SFN	0.012	0.099	-10000	0	-0.42	25	25
CDK2	0.036	0.03	-10000	0	-0.42	2	2
FOXO3A/14-3-3	0.016	0.12	-10000	0	-0.38	24	24
CREBBP	0.035	0.013	-10000	0	-0.099	1	1
FBXO32	0.023	0.3	-10000	0	-1.2	20	20
BCL6	-0.007	0.27	-10000	0	-1.1	21	21
RALB	0.033	0.041	-10000	0	-0.42	4	4
RALA	0.036	0.007	-10000	0	-10000	0	0
YWHAH	0.031	0.036	-10000	0	-0.42	3	3

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	-0.039	0.051	0.3	7	-10000	0	7
KIRREL	0.025	0.057	-10000	0	-0.43	7	7
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.04	0.051	-10000	0	-0.31	7	7
PLCG1	0.034	0.008	-10000	0	-10000	0	0
ARRB2	0.033	0.011	-10000	0	-10000	0	0
WASL	0.029	0.054	-10000	0	-0.42	7	7
Nephrin/NEPH1/podocin/CD2AP	0.065	0.059	-10000	0	-0.24	7	7
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.022	0.045	-10000	0	-0.21	13	13
FYN	0.057	0.1	0.28	66	-0.21	13	79
mol:Ca2+	0.059	0.057	-10000	0	-0.23	7	7
mol:DAG	0.06	0.058	-10000	0	-0.24	7	7
NPHS2	0.03	0.03	-10000	0	-0.43	1	1
mol:IP3	0.06	0.058	-10000	0	-0.24	7	7
regulation of endocytosis	0.046	0.057	-10000	0	-0.2	13	13
Nephrin/NEPH1/podocin/Cholesterol	0.049	0.049	-10000	0	-0.23	7	7
establishment of cell polarity	0.039	0.051	-10000	0	-0.3	7	7
Nephrin/NEPH1/podocin/NCK1-2	0.076	0.065	-10000	0	-0.22	8	8
Nephrin/NEPH1/beta Arrestin2	0.051	0.06	-10000	0	-0.2	13	13
NPHS1	0.041	0.03	-10000	0	-0.38	1	1
Nephrin/NEPH1/podocin	0.048	0.057	0.2	11	-0.21	13	24
TJP1	0.032	0.036	-10000	0	-0.42	3	3
NCK1	0.034	0.021	-10000	0	-0.42	1	1
NCK2	0.036	0.005	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.061	0.059	-10000	0	-0.24	7	7
CD2AP	0.035	0.007	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.061	0.059	-10000	0	-0.24	7	7
GRB2	0.033	0.011	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	0.057	0.1	0.28	68	-0.22	11	79
cytoskeleton organization	0.023	0.069	0.23	31	-0.25	7	38
Nephrin/NEPH1	0.035	0.037	-10000	0	-0.21	7	7
Nephrin/NEPH1/ZO-1	0.051	0.056	-10000	0	-0.25	10	10

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.015	0.063	-10000	0	-0.33	14	14
CRKL	0.031	0.041	-10000	0	-0.42	4	4
Rac1/GDP	0.026	0.004	-10000	0	-10000	0	0
DOCK1	0.028	0.057	-10000	0	-0.42	8	8
ITGA4	0.021	0.078	-10000	0	-0.42	15	15
alpha4/beta7 Integrin/MAdCAM1	0.069	0.075	-10000	0	-0.25	22	22
EPO	0.03	0.014	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.042	0.061	-10000	0	-0.3	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.032	0.023	-10000	0	-0.42	1	1
alpha4/beta1 Integrin	0.039	0.069	-10000	0	-0.33	16	16
EPO/EPOR (dimer)	0.048	0.014	-10000	0	-10000	0	0
lamellipodium assembly	0.013	0.084	-10000	0	-0.34	15	15
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
PI3K	0.036	0.065	-10000	0	-0.3	17	17
ARF6	0.034	0.029	-10000	0	-0.42	2	2
JAK2	0.024	0.049	-10000	0	-0.25	14	14
PXN	0.036	0.004	-10000	0	-10000	0	0
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
MADCAM1	0.034	0.008	-10000	0	-10000	0	0
cell adhesion	0.066	0.074	-10000	0	-0.25	22	22
CRKL/CBL	0.043	0.037	-10000	0	-0.3	4	4
ITGB1	0.032	0.036	-10000	0	-0.42	3	3
SRC	0.001	0.087	-10000	0	-0.27	39	39
ITGB7	0.036	0.005	-10000	0	-10000	0	0
RAC1	0.035	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.04	0.1	-10000	0	-0.3	37	37
p130Cas/Crk/Dock1	0.018	0.088	-10000	0	-0.25	27	27
VCAM1	0.009	0.1	-10000	0	-0.42	28	28
RHOA	0.026	0.061	-10000	0	-0.42	9	9
alpha4/beta1 Integrin/Paxillin/GIT1	0.073	0.068	-10000	0	-0.26	17	17
BCAR1	-0.024	0.075	0.18	16	-0.25	35	51
EPOR	0.036	0.005	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.032	0.012	-10000	0	-10000	0	0
GIT1	0.034	0.022	-10000	0	-0.42	1	1
Rac1/GTP	0.013	0.086	-10000	0	-0.35	15	15

×

TCGA08_rtk_signaling

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
PDGFRA	0.009	0.11	-10000	0	-0.42	29	29
HRAS	0.032	0.036	-10000	0	-0.42	3	3
EGFR	-0.015	0.13	-10000	0	-0.42	49	49
AKT	0.027	0.084	0.24	4	-0.24	18	22
FOXO3	0	0	-10000	0	-10000	0	0
AKT1	0.033	0.03	-10000	0	-0.42	2	2
FOXO1	0	0	-10000	0	-10000	0	0
AKT3	0.025	0.032	-10000	0	-0.42	2	2
FOXO4	0	0	-10000	0	-10000	0	0
MET	0.03	0.041	-10000	0	-0.42	4	4
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
PIK3CB	0.031	0.045	-10000	0	-0.42	5	5
NRAS	0.029	0.054	-10000	0	-0.42	7	7
PIK3CG	0.023	0.072	-10000	0	-0.42	13	13
PIK3R3	0.025	0.067	-10000	0	-0.42	11	11
PIK3R2	0.036	0.004	-10000	0	-10000	0	0
NF1	0.032	0.03	-10000	0	-0.42	2	2
RAS	-0.002	0.079	0.17	3	-0.26	26	29
ERBB2	0.017	0.078	-10000	0	-0.42	15	15
proliferation/survival/translation	-0.026	0.058	0.22	10	-0.18	5	15
PI3K	0.004	0.084	0.21	5	-0.23	35	40
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
KRAS	0.028	0.054	-10000	0	-0.42	7	7
FOXO	0.043	0.04	0.18	11	-10000	0	11
AKT2	0.036	0.005	-10000	0	-10000	0	0
PTEN	0.027	0.061	-10000	0	-0.42	9	9

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	0.024	0.17	-10000	0	-0.83	12	12
NCK1/PAK1/Dok-R	-0.028	0.076	-10000	0	-0.41	12	12
NCK1/Dok-R	0.031	0.15	-10000	0	-0.86	9	9
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
mol:beta2-estradiol	-0.007	0.015	0.31	1	-10000	0	1
RELA	0.035	0.006	-10000	0	-10000	0	0
SHC1	0.028	0.025	-10000	0	-0.42	1	1
Rac/GDP	0.026	0.004	-10000	0	-10000	0	0
F2	0.011	0.025	-10000	0	-10000	0	0
TNIP2	0.033	0.03	-10000	0	-0.42	2	2
NF kappa B/RelA	0.063	0.14	-10000	0	-0.79	9	9
FN1	-0.01	0.14	-10000	0	-0.42	50	50
PLD2	0.021	0.13	-10000	0	-0.85	9	9
PTPN11	0.036	0.004	-10000	0	-10000	0	0
GRB14	-0.063	0.18	-10000	0	-0.42	98	98
ELK1	0.024	0.13	-10000	0	-0.78	10	10
GRB7	0.024	0.058	-10000	0	-0.42	8	8
PAK1	0.015	0.085	-10000	0	-0.42	18	18
Tie2/Ang1/alpha5/beta1 Integrin	0.04	0.17	-10000	0	-0.88	9	9
CDKN1A	0.001	0.19	-10000	0	-0.73	26	26
ITGA5	0.034	0.029	-10000	0	-0.42	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.028	0.15	-10000	0	-0.86	9	9
CRK	0.032	0.023	-10000	0	-0.42	1	1
mol:NO	0.027	0.13	-10000	0	-0.6	12	12
PLG	0.019	0.13	-10000	0	-0.85	9	9
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.017	0.15	-10000	0	-0.8	11	11
GRB2	0.033	0.011	-10000	0	-10000	0	0
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
ANGPT2	-0.055	0.21	-10000	0	-0.69	28	28
BMX	0.009	0.15	-10000	0	-0.94	10	10
ANGPT1	0.015	0.035	-10000	0	-10000	0	0
tube development	-0.003	0.17	-10000	0	-0.66	19	19
ANGPT4	0.035	0.022	-10000	0	-0.42	1	1
response to hypoxia	0	0.01	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.009	0.16	-10000	0	-0.88	9	9
alpha5/beta1 Integrin	0.048	0.037	-10000	0	-0.3	5	5
FGF2	-0.001	0.11	-10000	0	-0.42	34	34
STAT5A (dimer)	-0.001	0.2	-10000	0	-0.77	23	23
mol:L-citrulline	0.027	0.13	-10000	0	-0.6	12	12
AGTR1	-0.046	0.16	-10000	0	-0.42	80	80
MAPK14	0.019	0.18	-10000	0	-1.1	11	11
Tie2/SHP2	0.011	0.17	-10000	0	-0.85	12	12
TEK	0.005	0.17	-10000	0	-0.96	11	11
RPS6KB1	0.036	0.16	-10000	0	-0.82	11	11
Angiotensin II/AT1	-0.03	0.12	-10000	0	-0.29	80	80
Tie2/Ang1/GRB2	0.034	0.14	-10000	0	-0.85	9	9
MAPK3	0.026	0.13	-10000	0	-0.78	9	9
MAPK1	0.016	0.12	-10000	0	-0.8	9	9
Tie2/Ang1/GRB7	0.03	0.14	-10000	0	-0.85	9	9
NFKB1	0.036	0.005	-10000	0	-10000	0	0
MAPK8	0.02	0.13	-10000	0	-0.85	9	9
PI3K	0.021	0.18	-10000	0	-0.96	12	12
FES	0.014	0.19	-10000	0	-1	13	13
Crk/Dok-R	0.03	0.15	-10000	0	-0.86	9	9
Tie2/Ang1/ABIN2	0.035	0.14	-10000	0	-0.86	9	9
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.026	0.15	-10000	0	-0.72	13	13
STAT5A	0.028	0.037	-10000	0	-0.42	3	3
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.055	0.17	-10000	0	-0.81	10	10
Tie2/Ang2	-0.012	0.21	-10000	0	-0.97	16	16
Tie2/Ang1	0.026	0.14	-10000	0	-0.9	9	9
FOXO1	0.026	0.16	-10000	0	-0.72	14	14
ELF1	0.034	0.053	-10000	0	-0.31	9	9
ELF2	0.027	0.13	-10000	0	-0.85	9	9
mol:Choline	0.02	0.12	-10000	0	-0.82	9	9
cell migration	-0.013	0.052	-10000	0	-0.22	15	15
FYN	-0.007	0.19	-10000	0	-0.77	18	18
DOK2	0.009	0.086	-10000	0	-0.42	19	19
negative regulation of cell cycle	0.005	0.18	-10000	0	-0.65	26	26
ETS1	0.035	0.028	-10000	0	-0.43	1	1
PXN	0.055	0.15	-10000	0	-0.65	11	11
ITGB1	0.032	0.036	-10000	0	-0.42	3	3
NOS3	0.024	0.14	-10000	0	-0.7	11	11
RAC1	0.035	0.006	-10000	0	-10000	0	0
TNF	0.033	0.065	-10000	0	-0.41	10	10
MAPKKK cascade	0.02	0.12	-10000	0	-0.82	9	9
RASA1	0.029	0.05	-10000	0	-0.42	6	6
Tie2/Ang1/Shc	0.028	0.14	-10000	0	-0.9	8	8
NCK1	0.034	0.021	-10000	0	-0.42	1	1
vasculogenesis	0.028	0.12	-10000	0	-0.52	13	13
mol:Phosphatidic acid	0.02	0.12	-10000	0	-0.82	9	9
mol:Angiotensin II	0.001	0.002	-10000	0	-10000	0	0
mol:NADP	0.027	0.13	-10000	0	-0.6	12	12
Rac1/GTP	0.034	0.16	-10000	0	-0.73	13	13
MMP2	0.011	0.14	-10000	0	-0.97	8	8

×

BARD1 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
BARD1/CSTF1	0.045	0.036	-10000	0	-0.3	4	4
ATM	0.031	0.013	-10000	0	-10000	0	0
UBE2D3	0.036	0.006	-10000	0	-10000	0	0
PRKDC	0.029	0.031	-10000	0	-0.42	2	2
ATR	0.036	0.006	-10000	0	-10000	0	0
UBE2L3	0.034	0.008	-10000	0	-10000	0	0
FANCD2	0.023	0.011	-10000	0	-10000	0	0
protein ubiquitination	0.06	0.073	-10000	0	-0.23	20	20
XRCC5	0.036	0.005	-10000	0	-10000	0	0
XRCC6	0.034	0.009	-10000	0	-10000	0	0
M/R/N Complex	0.048	0.044	-10000	0	-0.26	4	4
MRE11A	0.031	0.013	-10000	0	-10000	0	0
DNA-PK	0.056	0.037	-10000	0	-0.26	2	2
FA complex/FANCD2/Ubiquitin	0.003	0.093	-10000	0	-0.4	11	11
FANCF	0.032	0.041	-10000	0	-0.42	4	4
BRCA1	0.022	0.07	-10000	0	-0.42	12	12
CCNE1	0.027	0.046	-10000	0	-0.42	5	5
CDK2/Cyclin E1	0.044	0.045	-10000	0	-0.34	6	6
FANCG	0.035	0.006	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.037	0.062	-10000	0	-0.3	15	15
FANCE	0.032	0.036	-10000	0	-0.42	3	3
FANCC	0.035	0.021	-10000	0	-0.42	1	1
NBN	0.028	0.025	-10000	0	-0.42	1	1
FANCA	0.016	0.064	-10000	0	-0.42	10	10
DNA repair	-0.015	0.11	0.28	4	-0.35	16	20
BRCA1/BARD1/ubiquitin	0.037	0.062	-10000	0	-0.3	15	15
BARD1/DNA-PK	0.07	0.05	-10000	0	-0.23	5	5
FANCL	0.036	0.006	-10000	0	-10000	0	0
mRNA polyadenylation	-0.045	0.035	0.3	4	-10000	0	4
BRCA1/BARD1/CTIP/M/R/N Complex	0.017	0.08	-10000	0	-0.22	37	37
BRCA1/BACH1/BARD1/TopBP1	0.055	0.06	-10000	0	-0.26	15	15
BRCA1/BARD1/P53	0.05	0.091	-10000	0	-0.25	35	35
BARD1/CSTF1/BRCA1	0.049	0.06	-10000	0	-0.26	14	14
BRCA1/BACH1	0.021	0.07	-10000	0	-0.42	12	12
BARD1	0.033	0.035	-10000	0	-0.42	3	3
PCNA	0.03	0.046	-10000	0	-0.42	5	5
BRCA1/BARD1/UbcH5C	0.054	0.06	-10000	0	-0.26	15	15
BRCA1/BARD1/UbcH7	0.052	0.059	-10000	0	-0.26	14	14
BRCA1/BARD1/RAD51/PCNA	0.038	0.11	-10000	0	-0.24	59	59
BARD1/DNA-PK/P53	0.059	0.085	-10000	0	-0.22	29	29
BRCA1/BARD1/Ubiquitin	0.037	0.062	-10000	0	-0.3	15	15
BRCA1/BARD1/CTIP	0.034	0.061	-10000	0	-0.23	21	21
FA complex	0.02	0.056	-10000	0	-0.4	2	2
BARD1/EWS	0.047	0.031	-10000	0	-0.3	3	3
RBBP8	0.008	0.042	-10000	0	-0.3	9	9
TP53	0.008	0.1	-10000	0	-0.42	26	26
TOPBP1	0.036	0.006	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.048	0.089	0.24	35	-10000	0	35
BRCA1/BARD1	0.066	0.077	-10000	0	-0.23	20	20
CSTF1	0.032	0.023	-10000	0	-0.42	1	1
BARD1/EWS-Fli1	0.025	0.025	-10000	0	-0.3	3	3
CDK2	0.034	0.029	-10000	0	-0.42	2	2
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.006	0.13	-10000	0	-0.42	44	44
RAD50	0.032	0.041	-10000	0	-0.42	4	4
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.037	0.062	-10000	0	-0.3	15	15
EWSR1	0.034	0.009	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
EP300	0.032	0.03	-10000	0	-0.42	2	2
HDAC4	0.034	0.021	-10000	0	-0.42	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.005	0.017	-10000	0	-0.1	9	9
CDKN1A	-0.018	0.097	0.4	1	-0.56	14	15
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.035	0.007	-10000	0	-10000	0	0
FOXO3	-0.006	0.023	0.35	2	-10000	0	2
FOXO1	0	0	-10000	0	-10000	0	0
FOXO4	0.01	0.023	-10000	0	-0.33	2	2
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.034	0.009	-10000	0	-10000	0	0
TAT	0.027	0.016	-10000	0	-10000	0	0
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.005	0.064	-10000	0	-0.3	23	23
PPARGC1A	0.024	0.064	-10000	0	-0.42	10	10
FHL2	-0.022	0.15	-10000	0	-0.42	61	61
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.048	0.019	0.18	3	-10000	0	3
HIST2H4A	-0.005	0.017	0.1	9	-10000	0	9
SIRT1/FOXO3a	0.029	0.038	0.26	4	-0.2	2	6
SIRT1	0.035	0.019	0.21	4	-10000	0	4
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.054	0.037	-10000	0	-0.26	1	1
SIRT1/Histone H1b	0.021	0.077	0.18	1	-0.22	33	34
apoptosis	-0.064	0.025	-10000	0	-10000	0	0
SIRT1/PGC1A	0.038	0.045	0.16	4	-0.25	10	14
p53/SIRT1	0.026	0.077	0.4	4	-0.3	21	25
SIRT1/FOXO4	0.031	0.045	-10000	0	-0.2	6	6
FOXO1/FHL2/SIRT1	0.011	0.087	0.15	3	-0.22	59	62
HIST1H1E	0	0.066	-10000	0	-0.25	31	31
SIRT1/p300	0.047	0.028	-10000	0	-0.27	2	2
muscle cell differentiation	-0.009	0.06	0.25	23	-0.16	6	29
TP53	0.01	0.095	0.21	4	-0.42	22	26
KU70/SIRT1/BAX	0.065	0.025	-10000	0	-10000	0	0
CREBBP	0.033	0.011	-10000	0	-10000	0	0
MEF2D	0.029	0.015	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.041	0.024	-10000	0	-10000	0	0
ACSS2	0.015	0.02	0.19	4	-10000	0	4
SIRT1/PCAF/MYOD	0.01	0.061	0.16	7	-0.25	23	30

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.036	0.004	-10000	0	-10000	0	0
NFATC1	0.02	0.09	0.3	2	-0.39	7	9
NFATC2	0.018	0.049	0.16	1	-0.19	7	8
NFATC3	0.013	0.007	-10000	0	-10000	0	0
YWHAE	0.032	0.012	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.019	0.09	0.2	6	-0.36	10	16
Exportin 1/Ran/NUP214	0.069	0.023	-10000	0	-0.26	1	1
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.043	0.087	-10000	0	-0.38	6	6
BCL2/BAX	-0.018	0.14	-10000	0	-0.3	95	95
CaM/Ca2+/Calcineurin A alpha-beta B1	0.027	0.006	-10000	0	-10000	0	0
CaM/Ca2+	0.027	0.006	-10000	0	-10000	0	0
BAX	0.035	0.007	-10000	0	-10000	0	0
MAPK14	0.036	0.005	-10000	0	-10000	0	0
BAD	0.034	0.021	-10000	0	-0.42	1	1
CABIN1/MEF2D	0.03	0.082	0.2	3	-0.38	6	9
Calcineurin A alpha-beta B1/BCL2	-0.057	0.18	-10000	0	-0.42	99	99
FKBP8	0.036	0.006	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.03	0.081	0.38	6	-0.2	3	9
KPNB1	0.03	0.046	-10000	0	-0.42	5	5
KPNA2	0.025	0.058	-10000	0	-0.42	8	8
XPO1	0.036	0.005	-10000	0	-10000	0	0
SFN	0.012	0.099	-10000	0	-0.42	25	25
MAP3K8	0.004	0.11	-10000	0	-0.42	32	32
NFAT4/CK1 alpha	0.017	0.056	-10000	0	-0.21	23	23
MEF2D/NFAT1/Cbp/p300	0.056	0.065	-10000	0	-0.22	3	3
CABIN1	0.019	0.089	0.2	6	-0.37	9	15
CALM1	0.035	0.007	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	-10000	0	0
MAP3K1	0.01	0.099	-10000	0	-0.42	25	25
CAMK4	0.032	0.036	-10000	0	-0.42	3	3
mol:Ca2+	0.001	0.001	-10000	0	-10000	0	0
MAPK3	0.032	0.023	-10000	0	-0.42	1	1
YWHAH	0.031	0.036	-10000	0	-0.42	3	3
Calcineurin A alpha-beta B1/AKAP79/PKA	0.025	0.091	-10000	0	-0.3	36	36
YWHAB	0.035	0.008	-10000	0	-10000	0	0
MAPK8	0.033	0.035	-10000	0	-0.42	3	3
MAPK9	0.019	0.085	-10000	0	-0.42	18	18
YWHAG	0.036	0.005	-10000	0	-10000	0	0
FKBP1A	0.035	0.007	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.031	0.09	0.28	2	-0.34	8	10
PRKCH	0.03	0.046	-10000	0	-0.42	5	5
CABIN1/Cbp/p300	0.046	0.029	-10000	0	-0.29	2	2
CASP3	0.035	0.008	-10000	0	-10000	0	0
PIM1	0.035	0.007	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.024	0.005	-10000	0	-10000	0	0
apoptosis	0.003	0.049	-10000	0	-0.29	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.029	0.06	-10000	0	-0.24	4	4
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.03	0.05	-10000	0	-0.42	6	6
JNK2/NFAT4	-0.002	0.08	-10000	0	-0.23	18	18
BAD/BCL-XL	0.051	0.019	-10000	0	-0.3	1	1
PRKCD	0.033	0.03	-10000	0	-0.42	2	2
NUP214	0.035	0.021	-10000	0	-0.42	1	1
PRKCZ	0	0	-10000	0	-10000	0	0
PRKCA	0.032	0.012	-10000	0	-10000	0	0
PRKCG	0.036	0	-10000	0	-10000	0	0
PRKCQ	0.025	0.054	-10000	0	-0.42	7	7
FKBP38/BCL2	-0.019	0.14	-10000	0	-0.3	97	97
EP300	0.033	0.03	-10000	0	-0.42	2	2
PRKCB1	0.003	0.11	-10000	0	-0.42	30	30
CSNK2A1	0.035	0.006	-10000	0	-10000	0	0
NFATc/JNK1	0.037	0.094	0.31	2	-0.37	7	9
CaM/Ca2+/FKBP38	0.047	0.012	-10000	0	-10000	0	0
FKBP12/FK506	0.026	0.005	-10000	0	-10000	0	0
CSNK1A1	0.018	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.045	0.026	-10000	0	-0.25	3	3
NFATc/ERK1	0.033	0.091	0.31	2	-0.39	6	8
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.05	0.097	-10000	0	-0.32	12	12
NR4A1	0.062	0.078	0.23	12	-0.43	1	13
GSK3B	0.036	0.005	-10000	0	-10000	0	0
positive T cell selection	0.013	0.007	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.021	0.036	-10000	0	-0.18	2	2
RCH1/ KPNB1	0.038	0.056	-10000	0	-0.3	12	12
YWHAQ	0.034	0.029	-10000	0	-0.42	2	2
PRKACA	0.036	0.005	-10000	0	-10000	0	0
AKAP5	0	0.12	-10000	0	-0.42	37	37
MEF2D	0.029	0.015	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.027	0.016	-10000	0	-10000	0	0
NFATc/p38 alpha	0.037	0.092	0.33	1	-0.37	7	8
CREBBP	0.033	0.011	-10000	0	-10000	0	0
BCL2	-0.057	0.18	-10000	0	-0.42	99	99

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.031	0.041	-10000	0	-0.42	4	4
Rac1/GDP	0.035	0.013	-10000	0	-10000	0	0
DOCK1	0.028	0.057	-10000	0	-0.42	8	8
ITGA4	0.021	0.078	-10000	0	-0.42	15	15
RAC1	0.035	0.006	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.042	0.061	-10000	0	-0.3	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.032	0.023	-10000	0	-0.42	1	1
alpha4/beta1 Integrin	0.058	0.065	-10000	0	-0.28	16	16
alpha4/beta7 Integrin/Paxillin	0.049	0.051	-10000	0	-0.23	15	15
lamellipodium assembly	-0.013	0.13	-10000	0	-0.43	32	32
PIK3CA	0.033	0.022	-10000	0	-0.42	1	1
PI3K	0.036	0.065	-10000	0	-0.3	17	17
ARF6	0.034	0.029	-10000	0	-0.42	2	2
TLN1	0.035	0.021	-10000	0	-0.42	1	1
PXN	0.017	0.003	-10000	0	-10000	0	0
PIK3R1	0.019	0.08	-10000	0	-0.42	16	16
ARF6/GTP	0.059	0.064	-10000	0	-0.23	19	19
cell adhesion	0.062	0.063	-10000	0	-0.24	17	17
CRKL/CBL	0.043	0.037	-10000	0	-0.3	4	4
alpha4/beta1 Integrin/Paxillin	0.046	0.059	-10000	0	-0.26	16	16
ITGB1	0.032	0.036	-10000	0	-0.42	3	3
ITGB7	0.036	0.005	-10000	0	-10000	0	0
ARF6/GDP	0.033	0.031	-10000	0	-0.41	2	2
alpha4/beta1 Integrin/Paxillin/VCAM1	0.049	0.094	-10000	0	-0.26	37	37
p130Cas/Crk/Dock1	0.05	0.052	-10000	0	-0.25	9	9
VCAM1	0.009	0.1	-10000	0	-0.42	28	28
alpha4/beta1 Integrin/Paxillin/Talin	0.064	0.064	-10000	0	-0.25	17	17
alpha4/beta1 Integrin/Paxillin/GIT1	0.063	0.064	-10000	0	-0.24	17	17
BCAR1	0.03	0.014	-10000	0	-10000	0	0
mol:GDP	-0.061	0.063	0.24	17	-10000	0	17
CBL	0.032	0.012	-10000	0	-10000	0	0
PRKACA	0.036	0.005	-10000	0	-10000	0	0
GIT1	0.034	0.022	-10000	0	-0.42	1	1
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.064	0.064	-10000	0	-0.25	17	17
Rac1/GTP	-0.017	0.14	-10000	0	-0.48	32	32

×

Effects of Botulinum toxin

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
STX1A	0.009	0.002	-10000	0	-10000	0	0
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.046	0.027	-10000	0	-0.29	2	2
STXBP1	0.036	0.005	-10000	0	-10000	0	0
ACh/CHRNA1	0.016	0.044	-10000	0	-0.21	9	9
RAB3GAP2/RIMS1/UNC13B	0.051	0.04	-10000	0	-0.25	3	3
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	0.032	0.012	-10000	0	-10000	0	0
mol:ACh	-0.005	0.029	0.088	4	-0.11	18	22
RAB3GAP2	0.028	0.025	-10000	0	-0.42	1	1
STX1A/SNAP25/VAMP2	0.034	0.057	-10000	0	-0.18	3	3
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.016	0.044	-10000	0	-0.21	9	9
UNC13B	0.033	0.03	-10000	0	-0.42	2	2
CHRNA1	0.031	0.05	-10000	0	-0.42	6	6
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.042	0.11	-10000	0	-0.26	102	102
SNAP25	-0.001	0.043	-10000	0	-0.26	14	14
VAMP2	0.005	0.011	-10000	0	-0.23	1	1
SYT1	-0.062	0.17	-10000	0	-0.42	96	96
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.032	0.007	-10000	0	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.034	0.057	-10000	0	-0.18	3	3

×

Signaling events mediated by PRL

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
CCNE1	0.027	0.046	-10000	0	-0.42	5	5
mol:Halofuginone	0.004	0.009	-10000	0	-0.19	1	1
ITGA1	0.022	0.075	-10000	0	-0.42	14	14
CDKN1A	-0.005	0.12	-10000	0	-0.45	27	27
PRL-3/alpha Tubulin	0.02	0.018	-10000	0	-0.3	1	1
mol:Ca2+	-0.036	0.081	0.34	1	-0.31	38	39
AGT	-0.022	0.14	-10000	0	-0.42	52	52
CCNA2	-0.038	0.097	-10000	0	-0.52	3	3
TUBA1B	0	0	-10000	0	-10000	0	0
EGR1	-0.028	0.11	-10000	0	-0.29	77	77
CDK2/Cyclin E1	0.021	0.13	-10000	0	-0.39	31	31
MAPK3	0.012	0.016	-10000	0	-0.3	1	1
PRL-2 /Rab GGTase beta	0.047	0.04	-10000	0	-0.3	6	6
MAPK1	0.012	0.016	-10000	0	-0.3	1	1
PTP4A1	-0.028	0.085	-10000	0	-0.48	3	3
PTP4A3	0.027	0.025	-10000	0	-0.42	1	1
PTP4A2	0.03	0.05	-10000	0	-0.42	6	6
ITGB1	0.011	0.025	-10000	0	-0.3	3	3
SRC	0.033	0.029	-10000	0	-0.42	2	2
RAC1	0.013	0.059	-10000	0	-0.44	5	5
Rab GGTase beta/Rab GGTase alpha	0.051	0.013	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.001	0.098	0.37	1	-0.46	3	4
RABGGTA	0.035	0.007	-10000	0	-10000	0	0
BCAR1	-0.017	0.021	0.34	1	-10000	0	1
RHOC	0.01	0.071	-10000	0	-0.41	10	10
RHOA	0.001	0.092	-10000	0	-0.38	22	22
cell motility	0.012	0.087	0.35	1	-0.38	10	11
PRL-1/alpha Tubulin	-0.028	0.079	-10000	0	-0.45	3	3
PRL-3/alpha1 Integrin	0.032	0.06	-10000	0	-0.32	12	12
ROCK1	0.017	0.082	0.35	1	-0.39	9	10
RABGGTB	0.035	0.007	-10000	0	-10000	0	0
CDK2	0.034	0.029	-10000	0	-0.42	2	2
mitosis	-0.028	0.084	-10000	0	-0.48	3	3
ATF5	0.034	0.022	-10000	0	-0.42	1	1

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.075	0.048	-10000	0	-0.23	6	6
HDAC3	0.036	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.012	0.009	-10000	0	-0.19	1	1
GATA1/HDAC4	0.052	0.019	-10000	0	-0.3	1	1
GATA1/HDAC5	0.049	0.021	-10000	0	-0.3	1	1
GATA2/HDAC5	0.044	0.041	-10000	0	-0.3	6	6
HDAC5/BCL6/BCoR	0.048	0.075	-10000	0	-0.26	26	26
HDAC9	0.033	0.022	-10000	0	-0.42	1	1
Glucocorticoid receptor/Hsp90/HDAC6	0.04	0.048	-10000	0	-0.25	13	13
HDAC4/ANKRA2	0.04	0.059	-10000	0	-0.3	14	14
HDAC5/YWHAB	0.047	0.023	-10000	0	-0.3	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.016	0.011	-10000	0	-0.17	1	1
GATA2	0.029	0.046	-10000	0	-0.42	5	5
HDAC4/RFXANK	0.051	0.02	-10000	0	-0.3	1	1
BCOR	0.028	0.06	-10000	0	-0.42	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.032	0.03	-10000	0	-0.42	2	2
HDAC5	0.033	0.022	-10000	0	-0.42	1	1
GNB1/GNG2	0.048	0.039	-10000	0	-0.3	6	6
Histones	0.009	0.069	-10000	0	-0.22	32	32
ADRBK1	0.034	0.01	-10000	0	-10000	0	0
HDAC4	0.034	0.021	-10000	0	-0.42	1	1
XPO1	0.036	0.005	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.039	0.058	-10000	0	-0.3	13	13
HDAC4/Ubc9	0.046	0.024	-10000	0	-0.3	1	1
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.046	0.024	-10000	0	-0.3	1	1
TUBA1B	0	0	-10000	0	-10000	0	0
HDAC6	0.036	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.048	0.022	-10000	0	-0.3	1	1
CAMK4	0.032	0.036	-10000	0	-0.42	3	3
Tubulin/HDAC6	0.037	0.055	-10000	0	-0.25	17	17
SUMO1	0.036	0.005	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.035	0.008	-10000	0	-10000	0	0
GATA1	0.036	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.032	0.012	-10000	0	-10000	0	0
NR3C1	0.024	0.072	-10000	0	-0.42	13	13
SUMO1/HDAC4	0.052	0.042	-10000	0	-0.19	1	1
SRF	0.035	0.007	-10000	0	-10000	0	0
HDAC4/YWHAB	0.049	0.021	-10000	0	-0.3	1	1
Tubulin	0.015	0.058	-10000	0	-0.3	17	17
HDAC4/14-3-3 E	0.047	0.023	-10000	0	-0.29	1	1
GNB1	0.032	0.045	-10000	0	-0.42	5	5
RANGAP1	0.033	0.022	-10000	0	-0.42	1	1
BCL6/BCoR	0.032	0.08	-10000	0	-0.3	27	27
HDAC4/HDAC3/SMRT (N-CoR2)	0.069	0.023	-10000	0	-0.26	1	1
HDAC4/SRF	0.064	0.036	-10000	0	-0.26	4	4
HDAC4/ER alpha	-0.046	0.15	-10000	0	-0.3	133	133
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.009	0.068	-10000	0	-0.22	32	32
cell motility	0.036	0.055	-10000	0	-0.25	17	17
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.032	0.011	-10000	0	-10000	0	0
HDAC7/HDAC3	0.026	0.004	-10000	0	-10000	0	0
BCL6	0.018	0.085	-10000	0	-0.42	18	18
HDAC4/CaMK II delta B	0.034	0.021	-10000	0	-0.42	1	1
Hsp90/HDAC6	0.027	0	-10000	0	-10000	0	0
ESR1	-0.089	0.2	-10000	0	-0.42	132	132
HDAC6/HDAC11	0.035	0.077	-10000	0	-0.3	25	25
Ran/GTP/Exportin 1	0.054	0.041	-10000	0	-10000	0	0
NPC	0.021	0.003	-10000	0	-10000	0	0
MEF2C	0.015	0.091	-10000	0	-0.42	21	21
RAN	0.036	0.005	-10000	0	-10000	0	0
HDAC4/MEF2C	0.076	0.073	-10000	0	-0.22	19	19
GNG2	0.034	0.021	-10000	0	-0.42	1	1
NCOR2	0.036	0.005	-10000	0	-10000	0	0
TUBB2A	0.019	0.082	-10000	0	-0.42	17	17
HDAC11	0.013	0.099	-10000	0	-0.42	25	25
HSP90AA1	0	0	-10000	0	-10000	0	0
RANBP2	0.036	0.004	-10000	0	-10000	0	0
ANKRA2	0.023	0.072	-10000	0	-0.42	13	13
RFXANK	0.036	0.005	-10000	0	-10000	0	0
nuclear import	-0.037	0.028	0.26	2	-10000	0	2

×

a4b1 and a4b7 Integrin signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.032	0.036	-9999	-0.42	3	3
ITGB7	0.036	0.005	-9999	-10000	0	0
ITGA4	0.021	0.078	-9999	-0.42	15	15
alpha4/beta7 Integrin	0.042	0.061	-9999	-0.3	15	15
alpha4/beta1 Integrin	0.039	0.069	-9999	-0.33	16	16

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	-0.026	0.061	0.42	9	-10000	0	9
PI3K Class IB/PDE3B	0.026	0.061	-10000	0	-0.42	9	9
PDE3B	0.026	0.061	-10000	0	-0.42	9	9

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	0.035	0.007	-9999	-10000	0	0
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.033	0.011	-9999	-10000	0	0
TCEB1	0.028	0.025	-9999	-0.42	1	1
HIF1A/p53	0.007	0.098	-9999	-0.27	23	23
HIF1A	0	0.082	-9999	-0.28	17	17
COPS5	0.026	0.042	-9999	-0.42	4	4
VHL/Elongin B/Elongin C/RBX1/CUL2	0.072	0.053	-9999	-0.22	1	1
FIH (dimer)	0.036	0.005	-9999	-10000	0	0
CDKN2A	0.015	0.075	-9999	-0.42	14	14
ARNT/IPAS	0.051	0.013	-9999	-10000	0	0
HIF1AN	0.036	0.005	-9999	-10000	0	0
GNB2L1	0.034	0.035	-9999	-0.42	3	3
HIF1A/ARNT	0.019	0.088	-9999	-0.27	17	17
CUL2	0.035	0.007	-9999	-10000	0	0
OS9	0.034	0.029	-9999	-0.42	2	2
RACK1/Elongin B/Elongin C	0.054	0.038	-9999	-0.26	2	2
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.004	0.077	-9999	-0.27	17	17
PHD1-3/OS9	0.033	0.1	-9999	-0.24	49	49
HIF1A/RACK1/Elongin B/Elongin C	0.036	0.084	-9999	-0.34	2	2
VHL	0.035	0.007	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
HIF1A/JAB1	0.014	0.081	-9999	-0.27	13	13
EGLN3	-0.015	0.14	-9999	-0.42	52	52
EGLN2	0.032	0.041	-9999	-0.42	4	4
EGLN1	0.021	0.055	-9999	-0.42	7	7
TP53	0.008	0.1	-9999	-0.42	26	26
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.038	0.062	-9999	-0.44	5	5
ARNT	0.035	0.006	-9999	-10000	0	0
ARD1A	0.036	0.003	-9999	-10000	0	0
RBX1	0.034	0.009	-9999	-10000	0	0
HIF1A/p19ARF	0.004	0.093	-9999	-0.29	20	20

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.068	0.058	-10000	0	-0.26	9	9
MAP4K1	0.035	0.007	-10000	0	-10000	0	0
MAP3K8	0.004	0.11	-10000	0	-0.42	32	32
PRKCB	0	0	-10000	0	-10000	0	0
DBNL	0.034	0.029	-10000	0	-0.42	2	2
CRKL	0.031	0.041	-10000	0	-0.42	4	4
MAP3K1	0.004	0.07	-10000	0	-0.32	4	4
JUN	-0.01	0.1	-10000	0	-0.48	12	12
MAP3K7	0.013	0.059	0.21	3	-0.33	4	7
GRAP2	0.032	0.023	-10000	0	-0.42	1	1
CRK	0.032	0.023	-10000	0	-0.42	1	1
MAP2K4	-0.003	0.081	0.21	1	-0.34	13	14
LAT	0.03	0.031	-10000	0	-0.42	2	2
LCP2	0.024	0.067	-10000	0	-0.42	11	11
MAPK8	0.008	0.084	-10000	0	-0.58	9	9
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.02	0.067	-10000	0	-0.33	5	5
LAT/GRAP2/SLP76/HPK1/HIP-55	0.08	0.062	-10000	0	-0.24	9	9

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.017	0.003	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.042	0.031	-10000	0	-0.23	1	1
CDKN1B	0.01	0.077	0.26	2	-0.32	15	17
CDKN1A	0.012	0.071	-10000	0	-0.3	17	17
FRAP1	0.035	0.007	-10000	0	-10000	0	0
PRKDC	0.029	0.031	-10000	0	-0.42	2	2
FOXO3	0.012	0.056	-10000	0	-0.29	15	15
AKT1	0.012	0.059	-10000	0	-0.3	15	15
BAD	0.034	0.021	-10000	0	-0.42	1	1
AKT3	0.012	0.025	-10000	0	-0.29	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.012	0.056	-10000	0	-0.29	15	15
AKT1/ASK1	0.035	0.085	-10000	0	-0.28	15	15
BAD/YWHAZ	0.051	0.037	-10000	0	-0.26	1	1
RICTOR	0.035	0.007	-10000	0	-10000	0	0
RAF1	0.036	0.006	-10000	0	-10000	0	0
JNK cascade	-0.034	0.082	0.28	15	-10000	0	15
TSC1	0.014	0.061	-10000	0	-0.29	14	14
YWHAZ	0.027	0.016	-10000	0	-10000	0	0
AKT1/RAF1	0.053	0.08	0.28	2	-0.29	15	17
EP300	0.032	0.03	-10000	0	-0.42	2	2
mol:GDP	0.012	0.058	-10000	0	-0.3	15	15
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.008	0.061	0.26	1	-0.3	15	16
YWHAQ	0.034	0.029	-10000	0	-0.42	2	2
TBC1D4	0.005	0.034	0.24	2	-0.24	8	10
MAP3K5	0.012	0.095	-10000	0	-0.42	23	23
MAPKAP1	0.035	0.021	-10000	0	-0.42	1	1
negative regulation of cell cycle	-0.034	0.072	0.24	7	-0.2	1	8
YWHAH	0.031	0.036	-10000	0	-0.42	3	3
AKT1S1	0.018	0.074	0.27	1	-0.3	15	16
CASP9	0.016	0.055	-10000	0	-0.29	11	11
YWHAB	0.035	0.008	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.043	0.095	0.29	5	-0.36	8	13
GBL	0.032	0.023	-10000	0	-0.42	1	1
PDK1/Src/Hsp90	0.042	0.025	-10000	0	-0.25	2	2
YWHAE	0.032	0.012	-10000	0	-10000	0	0
SRC	0.033	0.029	-10000	0	-0.42	2	2
AKT2/p21CIP1	0.015	0.066	0.25	1	-0.33	7	8
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.035	0.073	-10000	0	-0.34	13	13
CHUK	0.01	0.069	-10000	0	-0.34	9	9
BAD/BCL-XL	0.056	0.079	0.28	2	-0.38	4	6
mTORC2	0.076	0.041	-10000	0	-0.23	2	2
AKT2	0.016	0.015	-10000	0	-0.28	1	1
FOXO1-3a-4/14-3-3 family	0.044	0.091	0.24	14	-0.29	8	22
PDPK1	0.032	0.023	-10000	0	-0.42	1	1
MDM2	0.017	0.068	0.26	2	-0.29	15	17
MAPKKK cascade	-0.053	0.079	0.28	15	-0.28	2	17
MDM2/Cbp/p300	0.055	0.082	0.28	7	-0.41	4	11
TSC1/TSC2	0.017	0.082	0.3	19	-0.36	7	26
proteasomal ubiquitin-dependent protein catabolic process	0.053	0.079	0.27	7	-0.39	4	11
glucose import	-0.001	0.03	0.21	2	-0.22	8	10
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.032	0.078	0.26	1	-0.44	6	7
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.001	0.031	0.21	2	-0.22	8	10
GSK3A	0.015	0.064	0.26	1	-0.29	15	16
FOXO1	0.012	0.056	-10000	0	-0.29	15	15
GSK3B	0.014	0.063	-10000	0	-0.29	15	15
SFN	0.012	0.099	-10000	0	-0.42	25	25
G1/S transition of mitotic cell cycle	0.019	0.071	0.26	3	-0.32	8	11
p27Kip1/14-3-3 family	0.021	0.054	-10000	0	-0.34	3	3
PRKACA	0.036	0.005	-10000	0	-10000	0	0
KPNA1	0.036	0.005	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
YWHAG	0.036	0.005	-10000	0	-10000	0	0
RHEB	0.035	0.007	-10000	0	-10000	0	0
CREBBP	0.033	0.011	-10000	0	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 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
SMAD4	0.029	0.054	-10000	0	-0.42	7	7
SMAD2	0	0.058	0.21	2	-0.22	12	14
SMAD3	0.019	0.058	0.28	1	-0.45	1	2
SMAD3/SMAD4	0.03	0.09	-10000	0	-0.38	17	17
SMAD4/Ubc9/PIASy	0.055	0.052	-10000	0	-0.26	10	10
SMAD2/SMAD2/SMAD4	0.051	0.079	-10000	0	-0.25	5	5
PPM1A	0.034	0.021	-10000	0	-0.42	1	1
CALM1	0.035	0.007	-10000	0	-10000	0	0
SMAD2/SMAD4	0.013	0.066	-10000	0	-0.21	21	21
MAP3K1	0.01	0.099	-10000	0	-0.42	25	25
TRAP-1/SMAD4	0.046	0.043	-10000	0	-0.3	7	7
MAPK3	0.032	0.023	-10000	0	-0.42	1	1
MAPK1	0.033	0.022	-10000	0	-0.42	1	1
NUP214	0.035	0.021	-10000	0	-0.42	1	1
CTDSP1	0.034	0.029	-10000	0	-0.42	2	2
CTDSP2	0.034	0.029	-10000	0	-0.42	2	2
CTDSPL	0.029	0.054	-10000	0	-0.42	7	7
KPNB1	0.03	0.046	-10000	0	-0.42	5	5
TGFBRAP1	0.036	0.004	-10000	0	-10000	0	0
UBE2I	0.032	0.011	-10000	0	-10000	0	0
NUP153	0.035	0.008	-10000	0	-10000	0	0
KPNA2	0.025	0.058	-10000	0	-0.42	8	8
PIAS4	0.033	0.036	-10000	0	-0.42	3	3

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.041	0.037	-10000	0	-0.25	7	7
EFNA5	0.03	0.046	-10000	0	-0.42	5	5
FYN	0.011	0.043	0.19	2	-0.23	14	16
neuron projection morphogenesis	0.041	0.037	-10000	0	-0.25	7	7
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.042	0.037	-10000	0	-0.25	7	7
EPHA5	0.034	0.029	-10000	0	-0.42	2	2

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.028	0.1	0.25	1	-0.27	25	26
CaM/Ca2+	0.026	0.005	-10000	0	-10000	0	0
AKT1	0.033	0.03	-10000	0	-0.42	2	2
AKT2	0.036	0.005	-10000	0	-10000	0	0
STXBP4	0.03	0.037	-10000	0	-0.42	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.008	0.099	0.22	2	-0.26	37	39
YWHAZ	0.027	0.016	-10000	0	-10000	0	0
CALM1	0.035	0.007	-10000	0	-10000	0	0
YWHAQ	0.034	0.029	-10000	0	-0.42	2	2
TBC1D4	0.009	0.042	-10000	0	-0.3	9	9
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.031	0.036	-10000	0	-0.42	3	3
YWHAB	0.035	0.008	-10000	0	-10000	0	0
SNARE/Synip	0.038	0.032	-10000	0	-0.25	4	4
YWHAG	0.036	0.005	-10000	0	-10000	0	0
ASIP	0	0	-10000	0	-10000	0	0
PRKCI	0.025	0.064	-10000	0	-0.42	10	10
AS160/CaM/Ca2+	0.026	0.005	-10000	0	-10000	0	0
RHOQ	0.031	0.045	-10000	0	-0.42	5	5
GYS1	0.018	0.04	0.25	12	-0.24	2	14
PRKCZ	0	0	-10000	0	-10000	0	0
TRIP10	0.032	0.041	-10000	0	-0.42	4	4
TC10/GTP/CIP4/Exocyst	0.042	0.041	-10000	0	-0.25	9	9
AS160/14-3-3	0.018	0.076	-10000	0	-0.28	12	12
VAMP2	0.031	0.023	-10000	0	-0.42	1	1
SLC2A4	0.006	0.11	0.23	2	-0.28	37	39
STX4	0	0	-10000	0	-10000	0	0
GSK3B	0.026	0.021	-10000	0	-0.28	2	2
SFN	0.012	0.099	-10000	0	-0.42	25	25
LNPEP	0.033	0.03	-10000	0	-0.42	2	2
YWHAE	0.032	0.012	-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	0.035	0.03	-10000	0	-0.42	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.045	0.1	0.26	12	-0.28	8	20
ERC1	0	0	-10000	0	-10000	0	0
RIP2/NOD2	0.021	0.011	-10000	0	-10000	0	0
NFKBIA	0.011	0.036	-10000	0	-0.37	3	3
BIRC2	0.032	0.012	-10000	0	-10000	0	0
IKBKB	0.03	0.014	-10000	0	-10000	0	0
RIPK2	0.028	0.015	-10000	0	-10000	0	0
IKBKG	0.011	0.099	-10000	0	-0.34	20	20
IKK complex/A20	0.033	0.12	-10000	0	-0.33	18	18
NEMO/A20/RIP2	0.028	0.015	-10000	0	-10000	0	0
XPO1	0.036	0.005	-10000	0	-10000	0	0
NEMO/ATM	0.022	0.11	-10000	0	-0.31	24	24
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.047	0.009	-10000	0	-10000	0	0
IKK complex/ELKS	0.011	0.1	-10000	0	-0.32	20	20
BCL10/MALT1/TRAF6	0.063	0.041	-10000	0	-0.31	4	4
NOD2	0	0	-10000	0	-10000	0	0
NFKB1	0.037	0.011	-10000	0	-0.1	1	1
RELA	0.037	0.011	-10000	0	-0.098	2	2
MALT1	0.031	0.041	-10000	0	-0.42	4	4
cIAP1/UbcH5C	0.046	0.019	-10000	0	-10000	0	0
ATM	0.031	0.013	-10000	0	-10000	0	0
TNF/TNFR1A	0.043	0.048	-10000	0	-0.3	9	9
TRAF6	0.035	0.021	-10000	0	-0.42	1	1
PRKCA	0.032	0.012	-10000	0	-10000	0	0
CHUK	0.026	0.067	-10000	0	-0.42	11	11
UBE2D3	0.036	0.006	-10000	0	-10000	0	0
TNF	0.026	0.061	-10000	0	-0.42	9	9
NF kappa B1 p50/RelA	0.074	0.037	-10000	0	-0.24	4	4
BCL10	0.035	0.008	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.011	0.036	-10000	0	-0.37	3	3
beta TrCP1/SCF ubiquitin ligase complex	0.035	0.03	-10000	0	-0.42	2	2
TNFRSF1A	0.033	0.022	-10000	0	-0.42	1	1
IKK complex	0.023	0.12	-10000	0	-0.34	19	19
CYLD	0.029	0.024	-10000	0	-0.42	1	1
IKK complex/PKC alpha	0.029	0.11	-10000	0	-0.32	17	17

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.03	0.024	-10000	0	-0.42	1	1
CLTC	0.025	0.063	0.26	2	-0.42	6	8
calcium ion-dependent exocytosis	0.017	0.038	-10000	0	-0.23	4	4
Dynamin 2/GTP	0.031	0.02	-10000	0	-0.23	2	2
EXOC4	0.034	0.021	-10000	0	-0.42	1	1
CD59	0.017	0.05	-10000	0	-0.36	5	5
CPE	-0.007	0.079	-10000	0	-0.26	43	43
CTNNB1	0.025	0.067	-10000	0	-0.42	11	11
membrane fusion	0.013	0.033	-10000	0	-0.23	4	4
CTNND1	0	0.056	0.2	33	-0.22	3	36
DNM2	0.036	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.02	0.047	0.19	2	-0.37	2	4
TSHR	0.013	0.034	-10000	0	-0.25	8	8
INS	0.008	0.096	-10000	0	-0.46	19	19
BIN1	0.035	0.021	-10000	0	-0.42	1	1
mol:Choline	0.013	0.033	-10000	0	-0.23	4	4
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.015	0.018	-10000	0	-0.25	2	2
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.034	0.029	-10000	0	-0.42	2	2
mol:Ca2+	0.031	0.02	-10000	0	-0.23	2	2
JUP	0.02	0.053	-10000	0	-0.37	5	5
ASAP2/amphiphysin II	0.043	0.023	-10000	0	-0.23	3	3
ARF6/GTP	0.025	0.021	-10000	0	-0.3	2	2
CDH1	-0.002	0.069	-10000	0	-0.41	5	5
clathrin-independent pinocytosis	0.025	0.021	-10000	0	-0.3	2	2
MAPK8IP3	0.024	0.061	-10000	0	-0.42	9	9
positive regulation of endocytosis	0.025	0.021	-10000	0	-0.3	2	2
EXOC2	0.029	0.05	-10000	0	-0.42	6	6
substrate adhesion-dependent cell spreading	0.018	0.075	-10000	0	-0.33	4	4
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.033	0.023	-10000	0	-0.42	1	1
regulation of calcium-dependent cell-cell adhesion	-0.031	0.086	0.4	5	-10000	0	5
positive regulation of phagocytosis	0.016	0.021	-10000	0	-0.25	3	3
ARF6/GTP/JIP3	0.036	0.046	-10000	0	-0.25	11	11
ACAP1	0.013	0.031	-10000	0	-0.21	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.017	0.045	-10000	0	-0.35	5	5
clathrin heavy chain/ACAP1	0.024	0.063	0.27	4	-0.32	6	10
JIP4/KLC1	0.04	0.025	-10000	0	-0.23	3	3
EXOC1	0.036	0.005	-10000	0	-10000	0	0
exocyst	0.018	0.075	-10000	0	-0.33	4	4
RALA/GTP	0.026	0.005	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.042	0.027	-10000	0	-0.25	3	3
receptor recycling	0.025	0.021	-10000	0	-0.3	2	2
CTNNA1	0	0.057	0.2	34	-0.22	3	37
NME1	0.015	0.018	-10000	0	-0.25	2	2
clathrin coat assembly	0.028	0.069	0.26	3	-0.39	7	10
IL2RA	0.009	0.067	-10000	0	-0.37	5	5
VAMP3	0.016	0.021	-10000	0	-0.25	3	3
GLUT4/clathrin heavy chain/ACAP1	0.031	0.06	-10000	0	-0.32	5	5
EXOC6	0.011	0.1	-10000	0	-0.42	27	27
PLD1	0.011	0.041	-10000	0	-0.27	9	9
PLD2	0.015	0.021	-10000	0	-0.24	2	2
EXOC5	0.035	0.021	-10000	0	-0.42	1	1
PIP5K1C	0.016	0.042	0.19	2	-0.37	2	4
SDC1	0.004	0.068	-10000	0	-0.42	5	5
ARF6/GDP	0.029	0.02	-10000	0	-0.25	2	2
EXOC7	0.033	0.01	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.033	0.089	-10000	0	-0.41	5	5
mol:Phosphatidic acid	0.013	0.033	-10000	0	-0.23	4	4
endocytosis	-0.041	0.023	0.22	3	-10000	0	3
SCAMP2	0.033	0.029	-10000	0	-0.42	2	2
ADRB2	0.012	0.087	0.26	1	-0.41	9	10
EXOC3	0.036	0.002	-10000	0	-10000	0	0
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.039	0.029	0.18	9	-0.23	2	11
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	0.023	0.068	0.26	1	-0.38	7	8
RALA	0.035	0.007	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.026	0.086	-10000	0	-0.39	5	5

×

Alternative NF-kappaB 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.041	0.057	-9999	-0.3	13	13
FBXW11	0.033	0.029	-9999	-0.42	2	2
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.033	0.029	-9999	-0.42	2	2
CHUK	0.026	0.067	-9999	-0.42	11	11
NF kappa B2 p100/RelB	0.082	0.075	-9999	-0.24	20	20
NFKB1	0.036	0.005	-9999	-10000	0	0
MAP3K14	0.032	0.03	-9999	-0.42	2	2
NF kappa B1 p50/RelB	0.047	0.04	-9999	-0.3	6	6
RELB	0.029	0.05	-9999	-0.42	6	6
NFKB2	0.035	0.021	-9999	-0.42	1	1
NF kappa B2 p52/RelB	0.042	0.036	-9999	-0.25	7	7
regulation of B cell activation	0.042	0.036	-9999	-0.25	7	7

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.034	0.088	-10000	0	-1.2	1	1
CLOCK	0.037	0.021	-10000	0	-0.42	1	1
TIMELESS/CRY2	0.042	0.061	-10000	0	-1.2	1	1
DEC1/BMAL1	0.043	0.061	-10000	0	-0.32	13	13
ATR	0.036	0.006	-10000	0	-10000	0	0
NR1D1	0.022	0.024	-10000	0	-10000	0	0
ARNTL	0.029	0.061	-10000	0	-0.42	9	9
TIMELESS	0.022	0.059	-10000	0	-1.3	1	1
NPAS2	0.027	0.064	-10000	0	-0.42	10	10
CRY2	0.036	0.005	-10000	0	-10000	0	0
mol:CO	-0.01	0.007	0.14	1	-10000	0	1
CHEK1	-0.001	0.11	-10000	0	-0.42	32	32
mol:HEME	0.01	0.007	-10000	0	-0.14	1	1
PER1	0.032	0.012	-10000	0	-10000	0	0
BMAL/CLOCK/NPAS2	0.067	0.07	-10000	0	-0.26	19	19
BMAL1/CLOCK	0.027	0.076	-10000	0	-0.49	3	3
S phase of mitotic cell cycle	0.034	0.088	-10000	0	-1.2	1	1
TIMELESS/CHEK1/ATR	0.035	0.09	-10000	0	-1.3	1	1
mol:NADPH	0.01	0.007	-10000	0	-0.14	1	1
PER1/TIMELESS	0.039	0.06	-10000	0	-1.2	1	1
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.031	0.045	-10000	0	-0.42	5	5

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.029	0.05	-9999	-0.42	6	6
Aurora C/Aurora B/INCENP	0.054	0.047	-9999	-0.23	10	10
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.013	0.03	-9999	-0.4	2	2
AURKB	0.029	0.037	-9999	-0.42	3	3
AURKC	0.034	0.021	-9999	-0.42	1	1

×

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	0.071	0.071	-10000	0	-0.27	11	11
Ran/GTP/Exportin 1/HDAC1	-0.012	0.009	-10000	0	-0.19	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.042	0.077	0.24	1	-0.3	11	12
SUMO1	0.036	0.005	-10000	0	-10000	0	0
ZFPM1	0.023	0.055	-10000	0	-0.42	7	7
NPC/RanGAP1/SUMO1/Ubc9	0.016	0.011	-10000	0	-0.17	1	1
FKBP3	0.033	0.035	-10000	0	-0.42	3	3
Histones	0.071	0.063	-10000	0	-0.3	2	2
YY1/LSF	0.029	0.061	-10000	0	-0.22	15	15
SMG5	0	0	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.027	0.039	-10000	0	-0.24	9	9
I kappa B alpha/HDAC1	0.04	0.056	-10000	0	-0.33	4	4
SAP18	0.034	0.01	-10000	0	-10000	0	0
RELA	0.022	0.052	0.28	1	-0.32	2	3
HDAC1/Smad7	0.067	0.028	-10000	0	-0.25	2	2
RANGAP1	0.033	0.022	-10000	0	-0.42	1	1
HDAC3/TR2	0.039	0.056	-10000	0	-0.25	8	8
NuRD/MBD3 Complex	0.032	0.067	-10000	0	-0.34	7	7
NF kappa B1 p50/RelA	0.037	0.073	0.25	1	-0.25	12	13
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.029	0.046	-10000	0	-0.42	5	5
GATA1	0.036	0	-10000	0	-10000	0	0
Mad/Max	0.052	0.011	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.018	0.092	-10000	0	-0.4	11	11
RBBP7	0.034	0.029	-10000	0	-0.42	2	2
NPC	0.021	0.003	-10000	0	-10000	0	0
RBBP4	0.035	0.021	-10000	0	-0.42	1	1
MAX	0.035	0.007	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.033	0.029	-10000	0	-0.42	2	2
NFKBIA	0.022	0.042	-10000	0	-0.37	4	4
KAT2B	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.021	0.057	-10000	0	-0.34	4	4
SIN3 complex	0.077	0.045	-10000	0	-0.23	5	5
SMURF1	0.036	0.006	-10000	0	-10000	0	0
CHD3	0.031	0.023	-10000	0	-0.42	1	1
SAP30	0.03	0.046	-10000	0	-0.42	5	5
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.032	0.012	-10000	0	-10000	0	0
YY1/HDAC3	0.028	0.049	-10000	0	-0.31	2	2
YY1/HDAC2	0.033	0.046	-10000	0	-0.22	6	6
YY1/HDAC1	0.035	0.047	-10000	0	-0.23	5	5
NuRD/MBD2 Complex (MeCP1)	0.032	0.066	-10000	0	-0.34	6	6
PPARG	0.01	0.093	0.3	1	-0.35	24	25
HDAC8/hEST1B	0.047	0.02	-10000	0	-0.25	2	2
UBE2I	0.032	0.011	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.033	0.029	-10000	0	-0.42	2	2
TNFRSF1A	0.033	0.022	-10000	0	-0.42	1	1
HDAC3/SMRT (N-CoR2)	0.042	0.05	-10000	0	-0.33	2	2
MBD3L2	0.028	0.057	-10000	0	-0.42	8	8
ubiquitin-dependent protein catabolic process	0.067	0.027	-10000	0	-0.25	2	2
CREBBP	0.033	0.011	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.035	0.079	-10000	0	-0.38	6	6
HDAC1	0.035	0.021	-10000	0	-0.42	1	1
HDAC3	0.025	0.029	-10000	0	-0.33	1	1
HDAC2	0.032	0.023	-10000	0	-0.42	1	1
YY1	0.016	0.018	-10000	0	-0.24	2	2
HDAC8	0.035	0.029	-10000	0	-0.42	2	2
SMAD7	0.034	0.021	-10000	0	-0.42	1	1
NCOR2	0.036	0.005	-10000	0	-10000	0	0
MXD1	0.036	0.005	-10000	0	-10000	0	0
STAT3	0.019	0.023	-10000	0	-0.28	2	2
NFKB1	0.036	0.005	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.036	0.004	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.047	0.063	-10000	0	-0.21	15	15
YY1/SAP30/HDAC1	0.048	0.058	-10000	0	-0.23	10	10
EP300	0.032	0.03	-10000	0	-0.42	2	2
STAT3 (dimer non-phopshorylated)	0.019	0.023	-10000	0	-0.28	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.022	0.042	-10000	0	-0.36	4	4
histone deacetylation	0.032	0.065	-10000	0	-0.33	6	6
STAT3 (dimer non-phopshorylated)/HDAC3	0.023	0.056	-10000	0	-0.4	3	3
nuclear export	-0.047	0.02	0.25	2	-10000	0	2
PRKACA	0.036	0.005	-10000	0	-10000	0	0
GATAD2B	0.028	0.025	-10000	0	-0.42	1	1
GATAD2A	0.036	0.006	-10000	0	-10000	0	0
GATA2/HDAC3	0.04	0.05	-10000	0	-0.26	5	5
GATA1/HDAC1	0.052	0.018	-10000	0	-0.3	1	1
GATA1/HDAC3	0.043	0.05	-10000	0	-0.34	2	2
CHD4	0.033	0.022	-10000	0	-0.42	1	1
TNF-alpha/TNFR1A	0.043	0.048	-10000	0	-0.3	9	9
SIN3/HDAC complex/Mad/Max	0.025	0.058	-10000	0	-0.32	5	5
NuRD Complex	0.037	0.076	-10000	0	-0.36	6	6
positive regulation of chromatin silencing	0.067	0.062	-10000	0	-0.3	2	2
SIN3B	0.036	0.005	-10000	0	-10000	0	0
MTA2	0.033	0.029	-10000	0	-0.42	2	2
SIN3A	0.035	0.007	-10000	0	-10000	0	0
XPO1	0.036	0.005	-10000	0	-10000	0	0
SUMO1/HDAC1	0.053	0.043	-10000	0	-0.27	1	1
HDAC complex	0.081	0.042	-10000	0	-0.23	5	5
GATA1/Fog1	0.038	0.046	-10000	0	-0.3	7	7
FKBP25/HDAC1/HDAC2	0.061	0.04	-10000	0	-0.26	5	5
TNF	0.026	0.061	-10000	0	-0.42	9	9
negative regulation of cell growth	0.025	0.058	-10000	0	-0.31	5	5
NuRD/MBD2/PRMT5 Complex	0.032	0.066	-10000	0	-0.34	6	6
Ran/GTP/Exportin 1	0.054	0.041	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.021	0.066	-10000	0	-0.31	11	11
SIN3/HDAC complex/NCoR1	0.017	0.06	-10000	0	-0.31	6	6
TFCP2	0.027	0.064	-10000	0	-0.42	10	10
NR2C1	0.03	0.05	-10000	0	-0.42	6	6
MBD3	0.035	0.008	-10000	0	-10000	0	0
MBD2	0.035	0.007	-10000	0	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.015	0.039	0.16	4	-0.18	1	5
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.021	0.043	0.15	9	-0.17	5	14
AP2	0.047	0.031	-10000	0	-0.3	3	3
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.042	0.035	-10000	0	-0.24	7	7
CLTB	0.034	0.021	-10000	0	-0.42	1	1
coatomer protein complex/ARF1/GTP/ER cargo protein	0.017	0.02	-10000	0	-0.22	2	2
CD4	0.034	0.009	-10000	0	-10000	0	0
CLTA	0.036	0.006	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-10000	0	0
ARFGAP1	0.008	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.019	0.033	0.17	5	-0.16	1	6
ARF1/GTP	0.016	0.017	-10000	0	-0.17	2	2
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.02	0.044	0.17	36	-0.19	1	37
mol:Choline	0.019	0.033	0.18	5	-0.16	1	6
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.028	0.026	-10000	0	-0.43	1	1
DDEF1	0.014	0.029	0.16	3	-0.17	1	4
ARF1/GDP	0.001	0.021	-10000	0	-0.1	5	5
AP2M1	0.032	0.036	-10000	0	-0.42	3	3
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.011	0.013	-10000	0	-0.23	1	1
Rac/GTP	0.028	0.007	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.032	0.028	-10000	0	-0.21	1	1
ARFIP2	0.021	0.053	-10000	0	-0.39	7	7
COPA	0.029	0.015	-10000	0	-10000	0	0
RAC1	0.035	0.006	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.016	0.028	-10000	0	-0.18	3	3
ARF1/GTP/ARHGAP10	0.018	0.016	-10000	0	-0.25	1	1
GGA3	0.032	0.023	-10000	0	-0.42	1	1
ARF1/GTP/Membrin	0.016	0.048	-10000	0	-0.24	15	15
AP2A1	0.035	0.007	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.01	0.03	-10000	0	-0.22	4	4
ARF1/GDP/Membrin	0.015	0.055	-10000	0	-0.26	16	16
Arfaptin 2/Rac/GDP	0.04	0.037	-10000	0	-0.24	7	7
CYTH2	-0.001	0.003	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.034	0.026	-10000	0	-0.26	1	1
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.026	0.004	-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	0.025	0.039	-10000	0	-0.4	2	2
PLD2	0.019	0.033	0.18	5	-0.17	1	6
ARF-GAP1/v-SNARE	0.008	0.003	-10000	0	-10000	0	0
PIP5K1A	0.019	0.033	0.17	5	-0.16	1	6
ARF1/GTP/Membrin/GBF1/p115	0.014	0.025	-10000	0	-0.22	1	1
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.019	0.033	0.18	5	-0.16	1	6
KDEL Receptor/Ligand/ARF-GAP1	0.008	0.003	-10000	0	-10000	0	0
GOSR2	0.018	0.038	-10000	0	-0.32	5	5
USO1	0.009	0.017	0.091	5	-0.063	2	7
GBF1	0.019	0.036	-10000	0	-0.32	4	4
ARF1/GTP/Arfaptin 2	0.035	0.032	-10000	0	-0.25	3	3
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.062	0.036	-10000	0	-0.26	3	3

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.056	0.04	-10000	0	-0.24	7	7
MAPK9	-0.001	0.056	-10000	0	-0.29	18	18
adrenocorticotropin secretion	0.005	0.024	-10000	0	-0.3	3	3
GNB1/GNG2	0.044	0.034	-10000	0	-0.25	6	6
GNB1	0.032	0.045	-10000	0	-0.42	5	5
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	0.009	0.001	-10000	0	-10000	0	0
Gs family/GTP	0.02	0.02	-10000	0	-0.22	3	3
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	0.002	0.005	0.062	3	-10000	0	3
GNAL	0.031	0.036	-10000	0	-0.42	3	3
GNG2	0.034	0.021	-10000	0	-0.42	1	1
CRH	0.026	0.038	-10000	0	-0.42	3	3
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.008	0.023	-10000	0	-0.29	3	3
MAPK11	0.009	0.003	-10000	0	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.035	0.021	-10000	0	-0.42	1	1
Ran/GTP/Exportin 1/HDAC4	0.006	0.014	-10000	0	-0.18	1	1
MDM2/SUMO1	0.05	0.042	-10000	0	-10000	0	0
HDAC4	0.034	0.021	-10000	0	-0.42	1	1
Ran/GTP/Exportin 1/HDAC1	0.006	0.015	-10000	0	-0.21	1	1
SUMO1	0.036	0.005	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1	0.014	0.018	-10000	0	-0.2	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	0.007	0.021	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.036	0.004	-10000	0	-10000	0	0
SUMO1/HDAC4	0.052	0.042	-10000	0	-0.19	1	1
SUMO1/HDAC1	0.053	0.043	-10000	0	-0.27	1	1
RANGAP1	0.033	0.022	-10000	0	-0.42	1	1
MDM2/SUMO1/SUMO1	0.081	0.036	-10000	0	-0.23	2	2
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.016	0.011	-10000	0	-0.17	1	1
Ran/GTP	0.036	0.038	-10000	0	-10000	0	0
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.034	0.009	-10000	0	-10000	0	0
UBE2I	0.032	0.011	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.034	0.038	0.2	4	-10000	0	4
NPC	0.021	0.003	-10000	0	-10000	0	0
PIAS2	0.033	0.03	-10000	0	-0.42	2	2
PIAS1	0.035	0.007	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0