Breast Invasive Carcinoma: PARADIGM pathway analysis of mRNA expression data

Pathway.Name	Avg.Num.Perturbations
Signaling events mediated by Stem cell factor receptor (c-Kit)	116
Signaling events regulated by Ret tyrosine kinase	113
Wnt signaling	99
FOXM1 transcription factor network	94
Syndecan-1-mediated signaling events	91
Endothelins	85
EGFR-dependent Endothelin signaling events	83
HIF-1-alpha transcription factor network	81
IGF1 pathway	81
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	79

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 mediated by Stem cell factor receptor (c-Kit)	116	9125	78	-0.39	0.17	1000	-1000	-0.045	-1000
Signaling events regulated by Ret tyrosine kinase	113	9321	82	-0.23	0.018	1000	-1000	-0.057	-1000
Wnt signaling	99	694	7	-0.13	-0.011	1000	-1000	-0.009	-1000
FOXM1 transcription factor network	94	4807	51	-0.43	0.024	1000	-1000	-0.11	-1000
Syndecan-1-mediated signaling events	91	3109	34	-0.19	0.018	1000	-1000	-0.009	-1000
Endothelins	85	8247	96	-0.25	0.018	1000	-1000	-0.051	-1000
EGFR-dependent Endothelin signaling events	83	1757	21	-0.17	0.024	1000	-1000	-0.046	-1000
HIF-1-alpha transcription factor network	81	6163	76	-0.25	0.025	1000	-1000	-0.05	-1000
IGF1 pathway	81	4658	57	-0.14	0.057	1000	-1000	-0.058	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	79	5394	68	-0.43	0.22	1000	-1000	-0.083	-1000
Plasma membrane estrogen receptor signaling	72	6228	86	-0.2	0.19	1000	-1000	-0.062	-1000
TCGA08_retinoblastoma	70	561	8	-0.052	0.026	1000	-1000	-0.005	-1000
FAS signaling pathway (CD95)	69	3246	47	-0.16	0.072	1000	-1000	-0.027	-1000
Glucocorticoid receptor regulatory network	68	7807	114	-0.54	0.28	1000	-1000	-0.05	-1000
Noncanonical Wnt signaling pathway	67	1757	26	-0.13	0.018	1000	-1000	-0.016	-1000
IL4-mediated signaling events	67	6157	91	-0.52	0.39	1000	-1000	-0.12	-1000
Fc-epsilon receptor I signaling in mast cells	67	6551	97	-0.15	0.038	1000	-1000	-0.056	-1000
IL27-mediated signaling events	65	3338	51	-0.27	0.17	1000	-1000	-0.053	-1000
IL6-mediated signaling events	65	4896	75	-0.18	0.043	1000	-1000	-0.029	-1000
TCR signaling in naïve CD8+ T cells	62	5789	93	-0.13	0.07	1000	-1000	-0.054	-1000
IL12-mediated signaling events	59	5182	87	-0.3	0.029	1000	-1000	-0.093	-1000
Osteopontin-mediated events	59	2262	38	-0.15	0.018	1000	-1000	-0.014	-1000
Arf6 signaling events	57	3588	62	-0.15	0.034	1000	-1000	-0.013	-1000
IL23-mediated signaling events	57	3423	60	-0.27	0.017	1000	-1000	-0.091	-1000
Thromboxane A2 receptor signaling	55	5871	105	-0.14	0.038	1000	-1000	-0.045	-1000
Stabilization and expansion of the E-cadherin adherens junction	54	4009	74	-0.14	0.03	1000	-1000	-0.06	-1000
Signaling events mediated by the Hedgehog family	52	2709	52	-0.16	0.056	1000	-1000	-0.015	-1000
Nongenotropic Androgen signaling	52	2742	52	-0.13	0.064	1000	-1000	-0.035	-1000
PLK2 and PLK4 events	49	149	3	-0.049	0.008	1000	-1000	-0.005	-1000
E-cadherin signaling events	49	249	5	-0.049	0.011	1000	-1000	-0.006	-1000
BMP receptor signaling	48	3902	81	-0.23	0.046	1000	-1000	-0.055	-1000
Syndecan-4-mediated signaling events	48	3263	67	-0.08	0.022	1000	-1000	-0.023	-1000
ErbB4 signaling events	44	3101	69	-0.17	0.097	1000	-1000	-0.058	-1000
Ephrin B reverse signaling	43	2083	48	-0.14	0.021	1000	-1000	-0.043	-1000
amb2 Integrin signaling	41	3384	82	-0.12	0.023	1000	-1000	-0.048	-1000
LPA receptor mediated events	41	4248	102	-0.13	0.018	1000	-1000	-0.045	-1000
Syndecan-2-mediated signaling events	40	2798	69	-0.072	0.022	1000	-1000	-0.018	-1000
IL2 signaling events mediated by PI3K	40	2376	58	-0.23	0.018	1000	-1000	-0.051	-1000
BCR signaling pathway	40	4036	99	-0.16	0.043	1000	-1000	-0.053	-1000
Caspase cascade in apoptosis	39	2894	74	-0.085	0.044	1000	-1000	-0.019	-1000
TCGA08_p53	39	277	7	-0.037	0.028	1000	-1000	-0.004	-1000
Signaling events mediated by PTP1B	38	2924	76	-0.15	0.055	1000	-1000	-0.046	-1000
Integrins in angiogenesis	37	3166	84	-0.18	0.031	1000	-1000	-0.057	-1000
Visual signal transduction: Rods	37	1959	52	-0.1	0.027	1000	-1000	-0.053	-1000
Canonical Wnt signaling pathway	36	1865	51	-0.25	0.098	1000	-1000	-0.032	-1000
Calcium signaling in the CD4+ TCR pathway	36	1132	31	-0.14	0.026	1000	-1000	-0.046	-1000
Ras signaling in the CD4+ TCR pathway	35	598	17	-0.038	0.013	1000	-1000	-0.017	-1000
Cellular roles of Anthrax toxin	34	1330	39	-0.14	0.018	1000	-1000	-0.012	-1000
Glypican 1 network	34	1635	48	-0.064	0.017	1000	-1000	-0.018	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	34	1532	45	-0.13	0.018	1000	-1000	-0.06	-1000
Glypican 2 network	34	138	4	-0.016	0	1000	-1000	-0.004	-1000
E-cadherin signaling in keratinocytes	34	1462	43	-0.079	0.018	1000	-1000	-0.017	-1000
Coregulation of Androgen receptor activity	33	2546	76	-0.18	0.029	1000	-1000	-0.022	-1000
IL1-mediated signaling events	33	2104	62	-0.082	0.051	1000	-1000	-0.054	-1000
Signaling mediated by p38-gamma and p38-delta	33	506	15	-0.07	0.014	1000	-1000	-0.005	-1000
Class IB PI3K non-lipid kinase events	33	99	3	-0.004	-1000	1000	-1000	-0.001	-1000
Regulation of nuclear SMAD2/3 signaling	32	4464	136	-0.2	0.066	1000	-1000	-0.024	-1000
Nectin adhesion pathway	32	2038	63	-0.11	0.024	1000	-1000	-0.054	-1000
Syndecan-3-mediated signaling events	32	1120	35	-0.099	0.033	1000	-1000	-0.024	-1000
E-cadherin signaling in the nascent adherens junction	32	2501	76	-0.078	0.024	1000	-1000	-0.054	-1000
Presenilin action in Notch and Wnt signaling	31	1941	61	-0.22	0.036	1000	-1000	-0.04	-1000
TRAIL signaling pathway	31	1523	48	-0.05	0.018	1000	-1000	-0.052	-1000
PDGFR-alpha signaling pathway	29	1294	44	-0.18	0.028	1000	-1000	-0.028	-1000
Reelin signaling pathway	29	1632	56	-0.089	0.038	1000	-1000	-0.052	-1000
Visual signal transduction: Cones	28	1097	38	-0.072	0.025	1000	-1000	-0.013	-1000
IFN-gamma pathway	27	1865	68	-0.086	0.023	1000	-1000	-0.06	-1000
Effects of Botulinum toxin	27	725	26	-0.17	0.019	1000	-1000	-0.009	-1000
IL2 signaling events mediated by STAT5	27	598	22	-0.073	0.021	1000	-1000	-0.018	-1000
Class I PI3K signaling events	27	2022	73	-0.089	0.031	1000	-1000	-0.031	-1000
Regulation of Telomerase	27	2802	102	-0.2	0.044	1000	-1000	-0.076	-1000
Insulin Pathway	27	2033	74	-0.16	0.05	1000	-1000	-0.057	-1000
Aurora B signaling	26	1787	67	-0.095	0.02	1000	-1000	-0.031	-1000
p75(NTR)-mediated signaling	25	3126	125	-0.13	0.036	1000	-1000	-0.056	-1000
FOXA2 and FOXA3 transcription factor networks	25	1178	46	-0.2	0.074	1000	-1000	-0.033	-1000
Ceramide signaling pathway	25	1967	76	-0.14	0.055	1000	-1000	-0.025	-1000
TCGA08_rtk_signaling	25	664	26	-0.079	0.039	1000	-1000	-0.006	-1000
PLK1 signaling events	24	2040	85	-0.1	0.028	1000	-1000	-0.032	-1000
RXR and RAR heterodimerization with other nuclear receptor	24	1299	52	-0.11	0.037	1000	-1000	-0.036	-1000
Regulation of Androgen receptor activity	22	1601	70	-0.18	0.026	1000	-1000	-0.045	-1000
Sphingosine 1-phosphate (S1P) pathway	21	613	28	-0.079	0.021	1000	-1000	-0.014	-1000
S1P1 pathway	21	788	36	-0.061	0.018	1000	-1000	-0.045	-1000
Angiopoietin receptor Tie2-mediated signaling	21	1881	88	-0.16	0.052	1000	-1000	-0.072	-1000
ErbB2/ErbB3 signaling events	20	1329	65	-0.059	0.024	1000	-1000	-0.042	-1000
mTOR signaling pathway	20	1062	53	-0.037	0.035	1000	-1000	-0.039	-1000
VEGFR1 specific signals	20	1120	56	-0.035	0.026	1000	-1000	-0.019	-1000
Aurora A signaling	19	1146	60	-0.037	0.034	1000	-1000	-0.011	-1000
Arf6 downstream pathway	19	848	43	-0.022	0.019	1000	-1000	-0.028	-1000
HIF-2-alpha transcription factor network	19	858	43	-0.081	0.082	1000	-1000	-0.053	-1000
EPHB forward signaling	19	1645	85	-0.039	0.038	1000	-1000	-0.053	-1000
PDGFR-beta signaling pathway	19	1882	97	-0.082	0.036	1000	-1000	-0.054	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	18	1015	54	-0.092	0.031	1000	-1000	-0.06	-1000
JNK signaling in the CD4+ TCR pathway	18	308	17	-0.036	0.029	1000	-1000	-0.018	-1000
ceramide signaling pathway	18	906	49	-0.11	0.037	1000	-1000	-0.025	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	18	599	33	-0.074	0.049	1000	-1000	-0.018	-1000
p38 MAPK signaling pathway	18	812	44	-0.078	0.034	1000	-1000	-0.052	-1000
BARD1 signaling events	17	970	57	-0.041	0.04	1000	-1000	-0.018	-1000
Hedgehog signaling events mediated by Gli proteins	17	1137	65	-0.051	0.041	1000	-1000	-0.043	-1000
Signaling events mediated by HDAC Class III	17	691	40	-0.077	0.034	1000	-1000	-0.014	-1000
Atypical NF-kappaB pathway	17	543	31	-0.074	0.028	1000	-1000	-0.019	-1000
Regulation of p38-alpha and p38-beta	17	964	54	-0.074	0.043	1000	-1000	-0.038	-1000
Signaling events mediated by PRL	17	602	34	-0.095	0.026	1000	-1000	-0.016	-1000
Retinoic acid receptors-mediated signaling	16	976	58	-0.085	0.04	1000	-1000	-0.05	-1000
Signaling mediated by p38-alpha and p38-beta	16	726	44	-0.09	0.025	1000	-1000	-0.015	-1000
Signaling events mediated by VEGFR1 and VEGFR2	16	2007	125	-0.06	0.055	1000	-1000	-0.065	-1000
S1P3 pathway	16	697	42	-0.079	0.021	1000	-1000	-0.015	-1000
Neurotrophic factor-mediated Trk receptor signaling	16	1990	120	-0.12	0.053	1000	-1000	-0.052	-1000
Paxillin-independent events mediated by a4b1 and a4b7	15	576	37	-0.023	0.028	1000	-1000	-0.018	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	15	1267	83	-0.11	0.057	1000	-1000	-0.026	-1000
LPA4-mediated signaling events	14	174	12	-0.03	0.015	1000	-1000	-0.007	-1000
a4b1 and a4b7 Integrin signaling	14	70	5	-0.007	0.018	1000	-1000	-0.005	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	14	1247	85	-0.14	0.039	1000	-1000	-0.051	-1000
EPO signaling pathway	13	745	55	-0.15	0.024	1000	-1000	-0.05	-1000
Signaling events mediated by HDAC Class II	12	949	75	-0.16	0.039	1000	-1000	-0.032	-1000
Paxillin-dependent events mediated by a4b1	12	432	36	-0.032	0.035	1000	-1000	-0.047	-1000
Nephrin/Neph1 signaling in the kidney podocyte	10	352	34	-0.009	0.035	1000	-1000	-0.015	-1000
Aurora C signaling	10	70	7	-0.007	0.016	1000	-1000	-0.022	-1000
Circadian rhythm pathway	9	201	22	-0.046	0.042	1000	-1000	-0.023	-1000
S1P5 pathway	9	161	17	-0.017	0.018	1000	-1000	-0.012	-1000
FoxO family signaling	9	612	64	-0.12	0.068	1000	-1000	-0.034	-1000
Alternative NF-kappaB pathway	9	117	13	0	0.034	1000	-1000	-0.008	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	8	193	23	-0.03	0.033	1000	-1000	-0.014	-1000
Canonical NF-kappaB pathway	8	344	39	-0.056	0.06	1000	-1000	-0.058	-1000
Ephrin A reverse signaling	8	60	7	0	0.015	1000	-1000	-0.004	-1000
Class I PI3K signaling events mediated by Akt	6	417	68	-0.038	0.052	1000	-1000	-0.026	-1000
Arf6 trafficking events	6	433	71	-0.021	0.031	1000	-1000	-0.045	-1000
S1P4 pathway	6	166	25	-0.017	0.021	1000	-1000	-0.015	-1000
Insulin-mediated glucose transport	5	175	32	-0.015	0.033	1000	-1000	-0.018	-1000
Signaling events mediated by HDAC Class I	5	542	104	-0.033	0.053	1000	-1000	-0.033	-1000
Rapid glucocorticoid signaling	5	117	20	-0.005	0.02	1000	-1000	-0.007	-1000
Arf1 pathway	3	165	54	-0.001	0.036	1000	-1000	-0.019	-1000
Sumoylation by RanBP2 regulates transcriptional repression	1	40	27	-0.001	0.04	1000	-1000	-0.037	-1000
Total	4471	264204	7203	-15	-990	131000	-131000	-4.7	-131000

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

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
MAP4K1	-0.15	0.21	-10000	0	-0.41	168	168
CRKL	-0.16	0.22	-10000	0	-0.45	165	165
HRAS	-0.12	0.19	-10000	0	-0.38	146	146
mol:PIP3	-0.15	0.2	0.24	1	-0.42	158	159
SPRED1	-0.002	0.098	-10000	0	-0.47	21	21
SPRED2	-0.003	0.1	-10000	0	-0.5	21	21
GAB1	-0.17	0.23	-10000	0	-0.47	168	168
FOXO3	-0.14	0.2	-10000	0	-0.42	154	154
AKT1	-0.16	0.21	-10000	0	-0.44	163	163
BAD	-0.14	0.2	-10000	0	-0.41	153	153
megakaryocyte differentiation	-0.17	0.23	-10000	0	-0.47	166	166
GSK3B	-0.14	0.2	-10000	0	-0.41	154	154
RAF1	-0.088	0.16	-10000	0	-0.31	140	140
SHC1	0.017	0.023	-10000	0	-0.52	1	1
STAT3	-0.17	0.22	-10000	0	-0.47	163	163
STAT1	-0.37	0.49	-10000	0	-0.92	206	206
HRAS/SPRED1	-0.095	0.17	-10000	0	-0.32	145	145
cell proliferation	-0.17	0.22	-10000	0	-0.45	165	165
PIK3CA	0.015	0.029	-10000	0	-0.34	3	3
TEC	0.013	0.052	-10000	0	-0.52	5	5
RPS6KB1	-0.17	0.22	-10000	0	-0.46	169	169
HRAS/SPRED2	-0.095	0.17	-10000	0	-0.34	107	107
LYN/TEC/p62DOK	-0.15	0.22	-10000	0	-0.45	163	163
MAPK3	-0.053	0.12	-10000	0	-0.26	59	59
STAP1	-0.19	0.24	-10000	0	-0.48	174	174
GRAP2	0.012	0.042	-10000	0	-0.28	10	10
JAK2	-0.31	0.4	-10000	0	-0.75	213	213
STAT1 (dimer)	-0.36	0.47	-10000	0	-0.89	206	206
mol:Gleevec	0.005	0.008	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.16	0.23	-10000	0	-0.45	168	168
actin filament polymerization	-0.17	0.22	-10000	0	-0.4	221	221
LYN	0.014	0.031	-10000	0	-0.25	7	7
STAP1/STAT5A (dimer)	-0.24	0.31	-10000	0	-0.64	166	166
PIK3R1	-0.01	0.11	-10000	0	-0.42	33	33
CBL/CRKL/GRB2	-0.13	0.2	-10000	0	-0.41	153	153
PI3K	-0.16	0.23	-10000	0	-0.45	168	168
PTEN	-0.001	0.1	-10000	0	-0.52	19	19
SCF/KIT/EPO/EPOR	-0.39	0.54	-10000	0	-1.2	152	152
MAPK8	-0.17	0.22	-10000	0	-0.46	165	165
STAT3 (dimer)	-0.17	0.22	-10000	0	-0.46	163	163
positive regulation of transcription	-0.042	0.1	0.17	1	-0.21	54	55
mol:GDP	-0.12	0.2	-10000	0	-0.39	153	153
PIK3C2B	-0.17	0.22	-10000	0	-0.47	164	164
CBL/CRKL	-0.14	0.21	-10000	0	-0.42	165	165
FER	-0.17	0.22	-10000	0	-0.47	163	163
SH2B3	-0.17	0.22	-10000	0	-0.46	163	163
PDPK1	-0.14	0.18	0.23	1	-0.39	152	153
SNAI2	-0.19	0.25	-10000	0	-0.5	177	177
positive regulation of cell proliferation	-0.27	0.36	-10000	0	-0.67	213	213
KITLG	-0.096	0.2	-10000	0	-0.45	123	123
cell motility	-0.27	0.36	-10000	0	-0.67	213	213
PTPN6	0.023	0.037	-10000	0	-0.43	3	3
EPOR	-0.091	0.16	-10000	0	-0.96	2	2
STAT5A (dimer)	-0.22	0.3	-10000	0	-0.56	213	213
SOCS1	0.015	0.031	-10000	0	-0.32	4	4
cell migration	0.17	0.22	0.45	174	-10000	0	174
SOS1	0.017	0.023	-10000	0	-0.52	1	1
EPO	-0.03	0.099	-10000	0	-0.26	80	80
VAV1	-0.014	0.12	-10000	0	-0.39	42	42
GRB10	-0.18	0.23	-10000	0	-0.47	167	167
PTPN11	0.022	0.024	-10000	0	-0.5	1	1
SCF/KIT	-0.18	0.23	-10000	0	-0.45	197	197
GO:0007205	0.008	0.011	-10000	0	-10000	0	0
MAP2K1	-0.063	0.13	-10000	0	-0.28	58	58
CBL	0.017	0.012	-10000	0	-0.25	1	1
KIT	-0.33	0.53	-10000	0	-1.2	121	121
MAP2K2	-0.064	0.13	-10000	0	-0.27	74	74
SHC/Grb2/SOS1	-0.14	0.22	-10000	0	-0.43	161	161
STAT5A	-0.23	0.31	-10000	0	-0.57	212	212
GRB2	0.016	0.024	-10000	0	-0.25	4	4
response to radiation	-0.19	0.24	-10000	0	-0.49	177	177
SHC/GRAP2	0.022	0.034	-10000	0	-0.37	2	2
PTPRO	-0.18	0.23	-10000	0	-0.48	166	166
SH2B2	-0.18	0.22	-10000	0	-0.41	221	221
DOK1	0.002	0.083	-10000	0	-0.41	19	19
MATK	-0.18	0.23	-10000	0	-0.46	174	174
CREBBP	0.003	0.059	-10000	0	-0.54	2	2
BCL2	-0.33	0.55	-10000	0	-1.3	125	125

×

Signaling events regulated by Ret tyrosine kinase

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.057	0.13	-9999	-0.74	13	13
Crk/p130 Cas/Paxillin	-0.17	0.18	-9999	-0.4	163	163
JUN	-0.17	0.21	-9999	-0.45	142	142
HRAS	0.012	0.051	-9999	-0.41	7	7
RET51/GFRalpha1/GDNF/GRB10	-0.21	0.22	-9999	-0.38	277	277
RAP1A	0.012	0.057	-9999	-0.52	6	6
FRS2	0.011	0.047	-9999	-0.27	13	13
RAP1A/GDP	0.009	0.041	-9999	-0.38	6	6
RET51/GFRalpha1/GDNF/DOK1	-0.21	0.22	-9999	-0.39	271	271
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.017	0.023	-9999	-0.52	1	1
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0.033	-9999	-0.52	2	2
RET9/GFRalpha1/GDNF/Enigma	-0.1	0.14	-9999	-0.28	188	188
RHOA	0.005	0.08	-9999	-0.52	12	12
RAP1A/GTP	-0.18	0.19	-9999	-0.36	245	245
GRB7	-0.017	0.1	-9999	-0.29	59	59
RET51/GFRalpha1/GDNF	-0.2	0.21	-9999	-0.38	265	265
MAPKKK cascade	-0.18	0.19	-9999	-0.45	145	145
BCAR1	0.017	0.012	-9999	-0.25	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.14	0.19	-9999	-0.35	199	199
lamellipodium assembly	-0.16	0.16	-9999	-0.34	208	208
RET51/GFRalpha1/GDNF/SHC	-0.2	0.21	-9999	-0.38	266	266
PIK3CA	0.016	0.029	-9999	-0.34	3	3
RET9/GFRalpha1/GDNF/SHC	-0.1	0.14	-9999	-0.28	189	189
RET9/GFRalpha1/GDNF/Shank3	-0.1	0.14	-9999	-0.28	190	190
MAPK3	-0.16	0.18	-9999	-0.43	135	135
DOK1	0.002	0.083	-9999	-0.41	19	19
DOK6	-0.028	0.14	-9999	-0.44	52	52
PXN	0.018	0	-9999	-10000	0	0
neurite development	-0.16	0.19	-9999	-0.41	146	146
DOK5	-0.028	0.14	-9999	-0.38	60	60
GFRA1	-0.22	0.24	-9999	-0.43	282	282
MAPK8	-0.16	0.2	-9999	-0.43	145	145
HRAS/GTP	-0.21	0.22	-9999	-0.52	145	145
tube development	-0.091	0.13	-9999	-0.26	193	193
MAPK1	-0.17	0.18	-9999	-0.43	135	135
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.079	0.12	-9999	-0.24	189	189
Rac1/GDP	0.013	0	-9999	-10000	0	0
SRC	0.015	0.035	-9999	-0.43	3	3
PDLIM7	0.017	0.012	-9999	-0.25	1	1
RET51/GFRalpha1/GDNF/Dok6	-0.2	0.23	-9999	-0.4	251	251
SHC1	0.017	0.023	-9999	-0.52	1	1
RET51/GFRalpha1/GDNF/Dok4	-0.2	0.21	-9999	-0.38	269	269
RET51/GFRalpha1/GDNF/Dok5	-0.22	0.23	-9999	-0.41	277	277
PRKCA	0.014	0.033	-9999	-0.25	8	8
HRAS/GDP	0.009	0.036	-9999	-0.29	7	7
CREB1	-0.14	0.19	-9999	-0.38	189	189
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.083	0.14	-9999	-0.25	192	192
RET51/GFRalpha1/GDNF/Grb7	-0.22	0.22	-9999	-0.4	275	275
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.18	0.23	-9999	-0.41	247	247
DOK4	0.013	0.047	-9999	-0.37	7	7
JNK cascade	-0.16	0.2	-9999	-0.44	142	142
RET9/GFRalpha1/GDNF/FRS2	-0.11	0.14	-9999	-0.28	190	190
SHANK3	0.016	0.033	-9999	-0.52	2	2
RASA1	0.004	0.078	-9999	-0.42	16	16
NCK1	0.011	0.045	-9999	-0.28	12	12
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.077	0.12	-9999	-0.23	189	189
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.16	0.19	-9999	-0.43	133	133
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.17	0.21	-9999	-0.46	143	143
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.18	0.23	-9999	-0.54	131	131
PI3K	-0.23	0.28	-9999	-0.53	217	217
SOS1	0.017	0.023	-9999	-0.52	1	1
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.09	0.14	-9999	-0.26	193	193
GRB10	-0.003	0.097	-9999	-0.43	24	24
activation of MAPKK activity	-0.13	0.16	-9999	-0.37	122	122
RET51/GFRalpha1/GDNF/FRS2	-0.2	0.21	-9999	-0.38	268	268
GAB1	0.006	0.074	-9999	-0.43	14	14
IRS1	-0.048	0.17	-9999	-0.49	68	68
IRS2	-0.026	0.13	-9999	-0.39	57	57
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.19	0.24	-9999	-0.55	136	136
RET51/GFRalpha1/GDNF/PKC alpha	-0.2	0.21	-9999	-0.38	265	265
GRB2	0.016	0.024	-9999	-0.25	4	4
PRKACA	0.018	0	-9999	-10000	0	0
GDNF	0.014	0.042	-9999	-0.45	4	4
RAC1	0.018	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.23	0.26	-9999	-0.43	274	274
Rac1/GTP	-0.19	0.2	-9999	-0.41	208	208
RET9/GFRalpha1/GDNF	-0.12	0.15	-9999	-0.32	188	188
GFRalpha1/GDNF	-0.15	0.18	-9999	-0.37	188	188

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.13	0.21	-9999	-0.34	214	214
FZD6	-0.077	0.2	-9999	-0.45	108	108
WNT6	-0.011	0.087	-9999	-0.26	54	54
WNT4	-0.062	0.18	-9999	-0.45	90	90
FZD3	-0.03	0.15	-9999	-0.48	51	51
WNT5A	-0.084	0.2	-9999	-0.43	120	120
WNT11	-0.013	0.089	-9999	-0.26	57	57

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.24	0.57	-10000	0	-1.1	118	118
PLK1	0.024	0.058	-10000	0	-10000	0	0
BIRC5	-0.092	0.39	-10000	0	-1.4	40	40
HSPA1B	-0.25	0.56	-10000	0	-1.1	128	128
MAP2K1	0.018	0.047	-10000	0	-0.3	1	1
BRCA2	-0.26	0.59	-10000	0	-1.1	124	124
FOXM1	-0.4	0.94	-10000	0	-1.7	127	127
XRCC1	-0.24	0.57	-10000	0	-1.1	111	111
FOXM1B/p19	-0.42	0.55	0.45	1	-1.2	142	143
Cyclin D1/CDK4	-0.3	0.57	-10000	0	-1	160	160
CDC2	-0.27	0.62	-10000	0	-1.2	118	118
TGFA	-0.29	0.55	-10000	0	-1	151	151
SKP2	-0.24	0.57	-10000	0	-1.1	118	118
CCNE1	-0.019	0.1	-10000	0	-0.29	64	64
CKS1B	-0.24	0.57	-10000	0	-1.1	122	122
RB1	-0.22	0.32	-10000	0	-0.84	80	80
FOXM1C/SP1	-0.31	0.67	-10000	0	-1.3	134	134
AURKB	0.011	0.13	-10000	0	-1.4	3	3
CENPF	-0.26	0.6	-10000	0	-1.2	115	115
CDK4	0.013	0.032	-10000	0	-0.26	5	5
MYC	-0.22	0.52	-10000	0	-0.97	130	130
CHEK2	0.011	0.073	-10000	0	-0.41	9	9
ONECUT1	-0.28	0.57	-10000	0	-1.1	144	144
CDKN2A	-0.056	0.15	-10000	0	-0.33	108	108
LAMA4	-0.24	0.58	-10000	0	-1.1	119	119
FOXM1B/HNF6	-0.37	0.71	-10000	0	-1.4	145	145
FOS	-0.34	0.64	-10000	0	-1.2	149	149
SP1	0.017	0.024	-10000	0	-0.52	1	1
CDC25B	-0.24	0.57	-10000	0	-1.1	112	112
response to radiation	0	0.039	-10000	0	-10000	0	0
CENPB	-0.24	0.57	-10000	0	-1.1	113	113
CENPA	-0.27	0.61	-10000	0	-1.2	112	112
NEK2	-0.29	0.62	-10000	0	-1.2	135	135
HIST1H2BA	-0.24	0.57	-10000	0	-1.1	116	116
CCNA2	-0.027	0.14	-10000	0	-0.4	57	57
EP300	0.014	0.047	-10000	0	-0.52	4	4
CCNB1/CDK1	-0.32	0.7	-10000	0	-1.4	114	114
CCNB2	-0.25	0.59	-10000	0	-1.1	122	122
CCNB1	-0.27	0.62	-10000	0	-1.2	119	119
ETV5	-0.25	0.58	-10000	0	-1.1	114	114
ESR1	-0.43	0.71	-10000	0	-1.2	219	219
CCND1	-0.31	0.6	-10000	0	-1.1	161	161
GSK3A	0.019	0.037	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.014	0.13	-10000	0	-0.35	53	53
CDK2	0.011	0.048	-10000	0	-0.31	10	10
G2/M transition of mitotic cell cycle	0	0.046	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.38	0.53	-10000	0	-1.2	133	133
GAS1	-0.32	0.64	-10000	0	-1.2	152	152
MMP2	-0.28	0.62	-10000	0	-1.2	129	129
RB1/FOXM1C	-0.31	0.6	-10000	0	-1.1	163	163
CREBBP	0.016	0.033	-10000	0	-0.52	2	2

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.017	0.023	-9999	-0.52	1	1
CCL5	-0.051	0.18	-9999	-0.49	71	71
SDCBP	0.003	0.081	-9999	-0.4	19	19
FGFR/FGF2/Syndecan-1	-0.17	0.27	-9999	-0.46	180	180
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.16	0.26	-9999	-0.54	126	126
Syndecan-1/Syntenin	-0.16	0.26	-9999	-0.53	129	129
MAPK3	-0.13	0.24	-9999	-0.52	109	109
HGF/MET	0.007	0.073	-9999	-0.38	13	13
TGFB1/TGF beta receptor Type II	0.017	0.023	-9999	-0.52	1	1
BSG	0.016	0.024	-9999	-0.25	4	4
keratinocyte migration	-0.15	0.25	-9999	-0.53	126	126
Syndecan-1/RANTES	-0.18	0.28	-9999	-0.52	159	159
Syndecan-1/CD147	-0.14	0.26	-9999	-0.54	117	117
Syndecan-1/Syntenin/PIP2	-0.15	0.25	-9999	-0.52	129	129
LAMA5	0.005	0.075	-9999	-0.41	15	15
positive regulation of cell-cell adhesion	-0.15	0.24	-9999	-0.5	129	129
MMP7	-0.095	0.21	-9999	-0.44	129	129
HGF	0.008	0.069	-9999	-0.45	11	11
Syndecan-1/CASK	-0.16	0.26	-9999	-0.44	180	180
Syndecan-1/HGF/MET	-0.15	0.26	-9999	-0.55	116	116
regulation of cell adhesion	-0.12	0.23	-9999	-0.51	106	106
HPSE	-0.015	0.12	-9999	-0.39	43	43
positive regulation of cell migration	-0.17	0.27	-9999	-0.46	180	180
SDC1	-0.17	0.27	-9999	-0.46	180	180
Syndecan-1/Collagen	-0.17	0.27	-9999	-0.46	180	180
PPIB	0.014	0.044	-9999	-0.41	5	5
MET	0	0.075	-9999	-0.29	31	31
PRKACA	0.018	0	-9999	-10000	0	0
MMP9	-0.042	0.17	-9999	-0.51	60	60
MAPK1	-0.13	0.24	-9999	-0.52	111	111
homophilic cell adhesion	-0.16	0.26	-9999	-0.45	180	180
MMP1	-0.19	0.22	-9999	-0.38	269	269

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.043	0.26	0.28	61	-0.44	112	173
PTK2B	0.017	0.017	-10000	0	-0.25	2	2
mol:Ca2+	-0.071	0.26	-10000	0	-0.7	50	50
EDN1	-0.065	0.24	0.23	61	-0.46	115	176
EDN3	-0.1	0.18	-10000	0	-0.32	190	190
EDN2	-0.13	0.22	-10000	0	-0.41	185	185
HRAS/GDP	-0.11	0.24	-10000	0	-0.48	112	112
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.087	0.22	-10000	0	-0.43	114	114
ADCY4	-0.043	0.21	-10000	0	-0.48	69	69
ADCY5	-0.06	0.22	-10000	0	-0.46	84	84
ADCY6	-0.041	0.21	-10000	0	-0.46	71	71
ADCY7	-0.046	0.22	-10000	0	-0.52	62	62
ADCY1	-0.04	0.21	-10000	0	-0.47	66	66
ADCY2	-0.075	0.24	-10000	0	-0.44	110	110
ADCY3	-0.044	0.21	-10000	0	-0.47	73	73
ADCY8	-0.043	0.21	-10000	0	-0.47	68	68
ADCY9	-0.05	0.22	-10000	0	-0.46	80	80
arachidonic acid secretion	-0.12	0.26	-10000	0	-0.52	122	122
ETB receptor/Endothelin-1/Gq/GTP	-0.079	0.18	-10000	0	-0.37	105	105
GNAO1	0.016	0.024	-10000	0	-0.25	4	4
HRAS	0.011	0.051	-10000	0	-0.41	7	7
ETA receptor/Endothelin-1/G12/GTP	-0.002	0.27	0.35	77	-0.47	81	158
ETA receptor/Endothelin-1/Gs/GTP	-0.007	0.26	0.33	77	-0.44	87	164
mol:GTP	-0.001	0.006	-10000	0	-10000	0	0
COL3A1	-0.048	0.28	-10000	0	-0.64	63	63
EDNRB	-0.03	0.13	-10000	0	-0.39	52	52
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.042	0.26	-10000	0	-0.62	58	58
CYSLTR1	-0.075	0.3	-10000	0	-0.6	95	95
SLC9A1	-0.01	0.15	-10000	0	-0.3	55	55
mol:GDP	-0.12	0.26	-10000	0	-0.5	121	121
SLC9A3	-0.13	0.34	-10000	0	-0.65	131	131
RAF1	-0.13	0.25	-10000	0	-0.52	116	116
JUN	-0.11	0.36	-10000	0	-0.98	62	62
JAK2	-0.043	0.26	0.28	61	-0.43	116	177
mol:IP3	-0.11	0.22	-10000	0	-0.46	113	113
ETA receptor/Endothelin-1	-0.019	0.32	0.42	77	-0.51	113	190
PLCB1	-0.086	0.18	-10000	0	-0.38	138	138
PLCB2	0.014	0.027	-10000	0	-0.39	2	2
ETA receptor/Endothelin-3	-0.074	0.19	-10000	0	-0.4	100	100
FOS	-0.18	0.35	-10000	0	-0.95	80	80
Gai/GDP	-0.007	0.14	-10000	0	-0.82	10	10
CRK	0.016	0.033	-10000	0	-0.52	2	2
mol:Ca ++	-0.14	0.32	-10000	0	-0.6	130	130
BCAR1	0.017	0.012	-10000	0	-0.25	1	1
PRKCB1	-0.13	0.24	-10000	0	-0.47	131	131
GNAQ	-0.001	0.007	-10000	0	-10000	0	0
GNAZ	0.001	0.088	-10000	0	-0.44	19	19
GNAL	0.011	0.052	-10000	0	-0.33	11	11
Gs family/GDP	-0.12	0.22	-10000	0	-0.46	115	115
ETA receptor/Endothelin-1/Gq/GTP	-0.068	0.23	-10000	0	-0.44	104	104
MAPK14	-0.084	0.17	-10000	0	-0.4	82	82
TRPC6	-0.077	0.28	-10000	0	-0.76	47	47
GNAI2	0.006	0.075	-10000	0	-0.48	12	12
GNAI3	0.018	0	-10000	0	-10000	0	0
GNAI1	-0.017	0.12	-10000	0	-0.38	46	46
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.096	0.18	-10000	0	-0.37	116	116
ETB receptor/Endothelin-2	-0.11	0.18	-10000	0	-0.4	135	135
ETB receptor/Endothelin-3	-0.09	0.16	-10000	0	-0.38	90	90
ETB receptor/Endothelin-1	-0.068	0.21	-10000	0	-0.39	121	121
MAPK3	-0.17	0.34	-10000	0	-0.81	94	94
MAPK1	-0.17	0.34	-10000	0	-0.81	94	94
Rac1/GDP	-0.1	0.24	-10000	0	-0.48	110	110
cAMP biosynthetic process	-0.047	0.22	0.27	1	-0.46	82	83
MAPK8	-0.089	0.29	-10000	0	-0.66	79	79
SRC	0.015	0.035	-10000	0	-0.43	3	3
ETB receptor/Endothelin-1/Gi/GTP	-0.037	0.15	-10000	0	-0.37	54	54
p130Cas/CRK/Src/PYK2	-0.1	0.25	-10000	0	-0.52	107	107
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.1	0.24	-10000	0	-0.48	110	110
COL1A2	-0.12	0.38	-10000	0	-0.81	99	99
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.095	0.22	-10000	0	-0.4	150	150
mol:DAG	-0.11	0.22	-10000	0	-0.46	113	113
MAP2K2	-0.15	0.28	-10000	0	-0.62	110	110
MAP2K1	-0.15	0.28	-10000	0	-0.62	106	106
EDNRA	-0.003	0.2	0.23	59	-0.54	53	112
positive regulation of muscle contraction	-0.031	0.22	0.25	56	-0.49	67	123
Gq family/GDP	-0.13	0.21	-10000	0	-0.51	95	95
HRAS/GTP	-0.12	0.23	-10000	0	-0.48	115	115
PRKCH	-0.099	0.22	-10000	0	-0.45	109	109
RAC1	0.018	0	-10000	0	-10000	0	0
PRKCA	-0.098	0.22	-10000	0	-0.45	105	105
PRKCB	-0.1	0.21	-10000	0	-0.44	116	116
PRKCE	-0.099	0.22	-10000	0	-0.44	112	112
PRKCD	-0.098	0.22	-10000	0	-0.45	107	107
PRKCG	-0.097	0.22	-10000	0	-0.45	106	106
regulation of vascular smooth muscle contraction	-0.21	0.41	-10000	0	-1.1	80	80
PRKCQ	-0.11	0.23	-10000	0	-0.47	112	112
PLA2G4A	-0.14	0.28	-10000	0	-0.57	122	122
GNA14	-0.081	0.18	-10000	0	-0.35	140	140
GNA15	0.001	0.077	-10000	0	-0.34	23	23
GNA12	0.018	0	-10000	0	-10000	0	0
GNA11	0.012	0.047	-10000	0	-0.52	4	4
Rac1/GTP	-0.002	0.27	0.35	77	-0.45	86	163
MMP1	-0.25	0.4	0.29	11	-0.66	210	221

×

EGFR-dependent Endothelin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.012	0.051	-9999	-0.41	7	7
EGFR	-0.079	0.18	-9999	-0.35	139	139
EGF/EGFR	-0.17	0.21	-9999	-0.36	244	244
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.085	0.16	-9999	-0.29	169	169
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.03	0.15	-9999	-0.5	49	49
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.14	0.23	-9999	-0.42	193	193
EGF/EGFR dimer/SHC	-0.12	0.18	-9999	-0.35	174	174
mol:GDP	-0.086	0.15	-9999	-0.29	169	169
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.097	0.21	-9999	-0.43	135	135
GRB2/SOS1	0.024	0.023	-9999	-0.37	1	1
HRAS/GTP	-0.1	0.12	-9999	-0.34	60	60
SHC1	0.017	0.023	-9999	-0.52	1	1
HRAS/GDP	-0.081	0.14	-9999	-0.35	60	60
FRAP1	-0.078	0.14	-9999	-0.35	58	58
EGF/EGFR dimer	-0.15	0.2	-9999	-0.42	173	173
SOS1	0.017	0.023	-9999	-0.52	1	1
GRB2	0.016	0.024	-9999	-0.25	4	4
ETA receptor/Endothelin-1	-0.089	0.19	-9999	-0.41	120	120

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.15	0.47	-9999	-0.91	105	105
HDAC7	0.001	0.006	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.13	0.39	-9999	-0.77	91	91
SMAD4	0.01	0.067	-9999	-0.49	9	9
ID2	-0.16	0.48	-9999	-0.92	107	107
AP1	-0.1	0.19	-9999	-0.44	107	107
ABCG2	-0.16	0.48	-9999	-0.92	109	109
HIF1A	-0.055	0.19	-9999	-0.53	59	59
TFF3	-0.23	0.52	-9999	-0.93	145	145
GATA2	-0.013	0.096	-9999	-0.33	40	40
AKT1	-0.006	0.1	-9999	-0.45	8	8
response to hypoxia	-0.02	0.084	-9999	-0.16	22	22
MCL1	-0.16	0.47	-9999	-0.9	108	108
NDRG1	-0.17	0.49	-9999	-0.93	110	110
SERPINE1	-0.17	0.48	-9999	-0.93	109	109
FECH	-0.16	0.48	-9999	-0.91	113	113
FURIN	-0.16	0.48	-9999	-0.92	107	107
NCOA2	0.009	0.063	-9999	-0.4	11	11
EP300	0.009	0.12	-9999	-0.38	12	12
HMOX1	-0.17	0.49	-9999	-0.92	113	113
BHLHE40	-0.17	0.46	-9999	-0.88	117	117
BHLHE41	-0.17	0.46	-9999	-0.88	117	117
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.008	0.16	-9999	-0.36	50	50
ENG	0.007	0.15	-9999	-0.34	46	46
JUN	-0.037	0.15	-9999	-0.47	57	57
RORA	-0.17	0.49	-9999	-0.92	115	115
ABCB1	-0.1	0.25	-9999	-1.1	26	26
TFRC	-0.18	0.49	-9999	-0.93	115	115
CXCR4	-0.18	0.49	-9999	-0.93	115	115
TF	-0.16	0.48	-9999	-0.91	108	108
CITED2	-0.16	0.48	-9999	-0.92	106	106
HIF1A/ARNT	-0.2	0.54	-9999	-1.1	99	99
LDHA	-0.043	0.15	-9999	-1.2	8	8
ETS1	-0.16	0.48	-9999	-0.91	110	110
PGK1	-0.16	0.47	-9999	-0.91	105	105
NOS2	-0.17	0.46	-9999	-0.88	117	117
ITGB2	-0.17	0.49	-9999	-0.93	114	114
ALDOA	-0.16	0.48	-9999	-0.92	107	107
Cbp/p300/CITED2	-0.16	0.48	-9999	-0.95	100	100
FOS	-0.11	0.2	-9999	-0.38	171	171
HK2	-0.16	0.47	-9999	-0.9	108	108
SP1	0.022	0.031	-9999	-0.52	1	1
GCK	0.011	0.2	-9999	-0.82	9	9
HK1	-0.16	0.47	-9999	-0.91	105	105
NPM1	-0.16	0.47	-9999	-0.91	105	105
EGLN1	-0.16	0.48	-9999	-0.92	108	108
CREB1	0.025	0.024	-9999	-0.52	1	1
PGM1	-0.16	0.48	-9999	-0.92	108	108
SMAD3	0.005	0.079	-9999	-0.41	17	17
EDN1	-0.22	0.48	-9999	-1.2	100	100
IGFBP1	-0.16	0.47	-9999	-0.91	108	108
VEGFA	-0.086	0.36	-9999	-0.69	91	91
HIF1A/JAB1	-0.038	0.14	-9999	-0.38	63	63
CP	-0.25	0.51	-9999	-0.95	136	136
CXCL12	-0.18	0.51	-9999	-0.97	115	115
COPS5	0.01	0.056	-9999	-0.35	11	11
SMAD3/SMAD4	0.013	0.074	-9999	-0.36	18	18
BNIP3	-0.16	0.48	-9999	-0.92	109	109
EGLN3	-0.2	0.5	-9999	-0.94	124	124
CA9	-0.17	0.49	-9999	-0.93	111	111
TERT	-0.16	0.48	-9999	-0.92	105	105
ENO1	-0.16	0.48	-9999	-0.92	106	106
PFKL	-0.16	0.48	-9999	-0.92	105	105
NCOA1	0.011	0.057	-9999	-0.52	6	6
ADM	-0.2	0.51	-9999	-0.94	125	125
ARNT	0.003	0.076	-9999	-10000	0	0
HNF4A	0.02	0.035	-9999	-0.52	2	2
ADFP	-0.17	0.49	-9999	-0.93	115	115
SLC2A1	-0.085	0.36	-9999	-0.69	89	89
LEP	-0.18	0.48	-9999	-0.9	118	118
HIF1A/ARNT/Cbp/p300	-0.13	0.4	-9999	-0.79	91	91
EPO	-0.092	0.35	-9999	-0.77	54	54
CREBBP	0.01	0.12	-9999	-0.36	10	10
HIF1A/ARNT/Cbp/p300/HDAC7	-0.13	0.39	-9999	-0.79	88	88
PFKFB3	-0.16	0.48	-9999	-0.93	107	107
NT5E	-0.16	0.48	-9999	-0.93	106	106

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.015	0.026	-10000	0	-0.25	5	5
PTK2	0.016	0.029	-10000	0	-0.34	3	3
CRKL	-0.1	0.19	-10000	0	-0.37	154	154
GRB2/SOS1/SHC	0.034	0.025	-10000	0	-0.3	2	2
HRAS	0.012	0.051	-10000	0	-0.41	7	7
IRS1/Crk	-0.1	0.19	-10000	0	-0.36	154	154
IGF-1R heterotetramer/IGF1/PTP1B	-0.11	0.18	-10000	0	-0.37	155	155
AKT1	-0.086	0.18	-10000	0	-0.42	84	84
BAD	-0.075	0.17	-10000	0	-0.39	84	84
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.1	0.19	-10000	0	-0.36	154	154
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.1	0.19	-10000	0	-0.37	155	155
RAF1	-0.063	0.16	-10000	0	-0.39	70	70
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.088	0.19	-10000	0	-0.34	153	153
YWHAZ	0.017	0.017	-10000	0	-0.25	2	2
IGF-1R heterotetramer/IGF1/IRS1	-0.12	0.2	-10000	0	-0.38	169	169
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
RPS6KB1	-0.086	0.18	-10000	0	-0.42	85	85
GNB2L1	0.015	0.04	-10000	0	-0.52	3	3
positive regulation of MAPKKK cascade	-0.058	0.14	0.22	1	-0.34	70	71
PXN	0.018	0	-10000	0	-10000	0	0
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.024	0.023	-10000	0	-0.37	1	1
HRAS/GTP	-0.099	0.15	-10000	0	-0.43	73	73
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.06	0.15	-10000	0	-0.35	71	71
IGF-1R heterotetramer	-0.1	0.22	-10000	0	-0.51	110	110
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.1	0.19	-10000	0	-0.37	152	152
Crk/p130 Cas/Paxillin	-0.078	0.18	-10000	0	-0.45	72	72
IGF1R	-0.1	0.22	-10000	0	-0.51	110	110
IGF1	-0.12	0.22	-10000	0	-0.44	146	146
IRS2/Crk	-0.11	0.2	-10000	0	-0.36	166	166
PI3K	-0.1	0.2	-10000	0	-0.36	164	164
apoptosis	0.057	0.15	0.34	84	-10000	0	84
HRAS/GDP	0.009	0.036	-10000	0	-0.29	7	7
PRKCD	-0.096	0.21	-10000	0	-0.44	117	117
RAF1/14-3-3 E	-0.048	0.14	-10000	0	-0.34	70	70
BAD/14-3-3	-0.061	0.16	-10000	0	-0.36	84	84
PRKCZ	-0.09	0.18	-10000	0	-0.32	164	164
Crk/p130 Cas/Paxillin/FAK1	-0.087	0.14	-10000	0	-0.39	67	67
PTPN1	0.002	0.07	-10000	0	-0.28	28	28
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.11	0.22	-10000	0	-0.41	153	153
BCAR1	0.017	0.012	-10000	0	-0.25	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.086	0.17	-10000	0	-0.32	163	163
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.017	0.023	-10000	0	-0.52	1	1
IRS1/NCK2	-0.1	0.19	-10000	0	-0.37	152	152
GRB10	-0.003	0.097	-10000	0	-0.43	24	24
PTPN11	-0.1	0.19	-10000	0	-0.37	152	152
IRS1	-0.12	0.2	-10000	0	-0.38	169	169
IRS2	-0.12	0.21	-10000	0	-0.39	165	165
IGF-1R heterotetramer/IGF1	-0.14	0.22	-10000	0	-0.46	156	156
GRB2	0.016	0.024	-10000	0	-0.25	4	4
PDPK1	-0.094	0.18	-10000	0	-0.33	164	164
YWHAE	0.016	0.029	-10000	0	-0.34	3	3
PRKD1	-0.12	0.23	-10000	0	-0.48	118	118
SHC1	0.017	0.023	-10000	0	-0.52	1	1

×

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	0.017	0.037	-10000	0	-0.43	2	2
NFATC2	-0.11	0.26	-10000	0	-0.6	77	77
NFATC3	-0.055	0.11	-10000	0	-0.24	67	67
CD40LG	-0.32	0.43	-10000	0	-0.89	156	156
ITCH	0.006	0.085	-10000	0	-10000	0	0
CBLB	0.005	0.088	-10000	0	-0.59	1	1
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.23	0.38	-10000	0	-0.91	87	87
JUNB	0.011	0.055	-10000	0	-0.36	10	10
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.008	0.1	-10000	0	-0.27	48	48
T cell anergy	-0.033	0.14	-10000	0	-0.39	48	48
TLE4	-0.071	0.23	-10000	0	-0.72	37	37
Jun/NFAT1-c-4/p21SNFT	-0.3	0.45	-10000	0	-0.91	147	147
AP-1/NFAT1-c-4	-0.37	0.52	-10000	0	-1	156	156
IKZF1	-0.08	0.23	-10000	0	-0.71	40	40
T-helper 2 cell differentiation	-0.22	0.35	-10000	0	-0.79	112	112
AP-1/NFAT1	-0.14	0.24	-10000	0	-0.52	112	112
CALM1	0.003	0.058	-10000	0	-10000	0	0
EGR2	-0.29	0.52	-10000	0	-1.2	92	92
EGR3	-0.37	0.58	-10000	0	-1.2	141	141
NFAT1/FOXP3	-0.064	0.2	-10000	0	-0.57	39	39
EGR1	-0.1	0.2	-10000	0	-0.39	156	156
JUN	-0.035	0.15	-10000	0	-0.46	57	57
EGR4	0	0.007	-10000	0	-10000	0	0
mol:Ca2+	-0.016	0.06	-10000	0	-10000	0	0
GBP3	-0.14	0.31	-10000	0	-0.75	94	94
FOSL1	0.016	0.024	-10000	0	-0.25	4	4
NFAT1-c-4/MAF/IRF4	-0.28	0.44	-10000	0	-0.86	157	157
DGKA	-0.066	0.21	-10000	0	-0.68	34	34
CREM	0.016	0.017	-10000	0	-0.26	2	2
NFAT1-c-4/PPARG	-0.3	0.46	-10000	0	-0.9	162	162
CTLA4	-0.052	0.18	-10000	0	-0.53	40	40
NFAT1-c-4 (dimer)/EGR1	-0.33	0.48	-10000	0	-0.95	161	161
NFAT1-c-4 (dimer)/EGR4	-0.28	0.44	-10000	0	-0.88	157	157
FOS	-0.11	0.2	-10000	0	-0.39	152	152
IFNG	-0.3	0.47	-10000	0	-1.1	94	94
T cell activation	-0.17	0.29	-10000	0	-0.75	64	64
MAF	-0.012	0.12	-10000	0	-0.44	35	35
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.22	0.38	0.73	152	-10000	0	152
TNF	-0.3	0.42	-10000	0	-0.88	144	144
FASLG	-0.43	0.65	-10000	0	-1.3	166	166
TBX21	-0.11	0.21	-10000	0	-0.46	137	137
BATF3	0	0.001	-10000	0	-10000	0	0
PRKCQ	-0.018	0.11	-10000	0	-0.32	51	51
PTPN1	-0.069	0.2	-10000	0	-0.64	36	36
NFAT1-c-4/ICER1	-0.28	0.44	-10000	0	-0.88	156	156
GATA3	-0.1	0.23	-10000	0	-0.51	124	124
T-helper 1 cell differentiation	-0.28	0.44	-10000	0	-1.1	97	97
IL2RA	-0.25	0.35	-10000	0	-0.87	93	93
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.058	0.19	-10000	0	-0.61	31	31
E2F1	0.013	0.071	-10000	0	-0.36	16	16
PPARG	-0.036	0.14	-10000	0	-0.33	81	81
SLC3A2	-0.06	0.19	-10000	0	-0.61	32	32
IRF4	-0.01	0.085	-10000	0	-0.26	52	52
PTGS2	-0.33	0.44	-10000	0	-0.9	157	157
CSF2	-0.33	0.43	-10000	0	-0.9	156	156
JunB/Fra1/NFAT1-c-4	-0.26	0.43	-10000	0	-0.84	156	156
IL4	-0.24	0.37	-10000	0	-0.85	106	106
IL5	-0.32	0.43	-10000	0	-0.89	155	155
IL2	-0.18	0.29	-10000	0	-0.78	61	61
IL3	-0.04	0.052	-10000	0	-10000	0	0
RNF128	-0.053	0.2	-10000	0	-0.6	47	47
NFATC1	-0.22	0.39	-10000	0	-0.73	152	152
CDK4	0.14	0.22	0.57	51	-10000	0	51
PTPRK	-0.12	0.3	-10000	0	-0.73	86	86
IL8	-0.36	0.44	-10000	0	-0.93	158	158
POU2F1	0.027	0	-10000	0	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.058	0.14	-10000	0	-0.26	154	154
ER alpha/Gai/GDP/Gbeta gamma	-0.089	0.19	-10000	0	-0.35	156	156
AKT1	-0.2	0.35	-10000	0	-0.74	151	151
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.2	0.35	-10000	0	-0.75	151	151
mol:Ca2+	-0.1	0.18	-10000	0	-0.44	88	88
IGF1R	-0.083	0.2	-10000	0	-0.47	110	110
E2/ER alpha (dimer)/Striatin	-0.09	0.15	-10000	0	-0.32	155	155
SHC1	0.017	0.023	-10000	0	-0.52	1	1
apoptosis	0.19	0.33	0.7	151	-10000	0	151
RhoA/GTP	-0.086	0.12	-10000	0	-0.41	27	27
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.12	0.18	-10000	0	-0.38	154	154
regulation of stress fiber formation	0.041	0.12	0.29	41	-10000	0	41
E2/ERA-ERB (dimer)	-0.086	0.15	-10000	0	-0.31	150	150
KRAS	0.009	0.065	-10000	0	-0.44	10	10
G13/GTP	-0.08	0.14	-10000	0	-0.29	151	151
pseudopodium formation	-0.041	0.12	-10000	0	-0.29	41	41
E2/ER alpha (dimer)/PELP1	-0.086	0.15	-10000	0	-0.31	150	150
GRB2	0.016	0.024	-10000	0	-0.25	4	4
GNG2	0.016	0.029	-10000	0	-0.34	3	3
GNAO1	0.016	0.024	-10000	0	-0.25	4	4
HRAS	0.012	0.051	-10000	0	-0.41	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.11	0.22	-10000	0	-0.44	152	152
E2/ER beta (dimer)	0.013	0.008	-10000	0	-0.17	1	1
mol:GDP	-0.12	0.17	-10000	0	-0.39	150	150
mol:NADP	-0.11	0.22	-10000	0	-0.44	152	152
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
mol:IP3	-0.11	0.19	-10000	0	-0.46	88	88
IGF-1R heterotetramer	-0.083	0.2	-10000	0	-0.47	110	110
PLCB1	-0.12	0.19	-10000	0	-0.48	87	87
PLCB2	-0.074	0.17	-10000	0	-0.53	53	53
IGF1	-0.1	0.2	-10000	0	-0.41	146	146
mol:L-citrulline	-0.11	0.22	-10000	0	-0.44	152	152
RHOA	0.005	0.08	-10000	0	-0.52	12	12
Gai/GDP	-0.008	0.12	-10000	0	-0.75	10	10
JNK cascade	0.013	0.008	-10000	0	-0.17	1	1
BCAR1	0.017	0.012	-10000	0	-0.25	1	1
ESR2	0.017	0.012	-10000	0	-0.25	1	1
GNAQ	0	0	-10000	0	-10000	0	0
ESR1	-0.16	0.24	-10000	0	-0.46	199	199
Gq family/GDP/Gbeta gamma	-0.024	0.12	-10000	0	-0.49	19	19
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.044	0.13	-10000	0	-0.63	2	2
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.12	0.18	-10000	0	-0.38	155	155
GNAZ	0.001	0.088	-10000	0	-0.44	19	19
E2/ER alpha (dimer)	-0.12	0.17	-10000	0	-0.33	199	199
STRN	0.011	0.056	-10000	0	-0.42	8	8
GNAL	0.011	0.052	-10000	0	-0.33	11	11
PELP1	0.018	0	-10000	0	-10000	0	0
MAPK11	0.021	0.007	-10000	0	-10000	0	0
GNAI2	0.006	0.075	-10000	0	-0.48	12	12
GNAI3	0.018	0	-10000	0	-10000	0	0
GNAI1	-0.017	0.12	-10000	0	-0.38	46	46
HBEGF	-0.093	0.19	-10000	0	-0.43	65	65
cAMP biosynthetic process	-0.081	0.11	-10000	0	-0.25	152	152
SRC	-0.079	0.18	-10000	0	-0.42	42	42
PI3K	0.005	0.082	-10000	0	-0.37	21	21
GNB1	0.013	0.052	-10000	0	-0.52	5	5
G13/GDP/Gbeta gamma	-0.1	0.15	-10000	0	-0.33	151	151
SOS1	0.017	0.023	-10000	0	-0.52	1	1
IGF-1R heterotetramer/IGF1	-0.16	0.21	-10000	0	-0.44	167	167
Gs family/GTP	-0.066	0.13	-10000	0	-0.26	152	152
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.019	0.064	-10000	0	-0.28	20	20
vasodilation	-0.1	0.22	-10000	0	-0.42	152	152
mol:DAG	-0.11	0.19	-10000	0	-0.46	88	88
Gs family/GDP/Gbeta gamma	-0.1	0.15	-10000	0	-0.32	152	152
MSN	-0.045	0.13	-10000	0	-0.32	41	41
Gq family/GTP	-0.084	0.18	-10000	0	-0.57	52	52
mol:PI-3-4-5-P3	-0.19	0.34	-10000	0	-0.72	151	151
NRAS	0.005	0.076	-10000	0	-0.4	16	16
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.1	0.22	0.42	152	-10000	0	152
GRB2/SOS1	0.024	0.023	-10000	0	-0.37	1	1
RhoA/GDP	-0.093	0.18	-10000	0	-0.37	151	151
NOS3	-0.11	0.23	-10000	0	-0.46	152	152
GNA11	0.014	0.047	-10000	0	-0.52	4	4
MAPKKK cascade	-0.12	0.26	-10000	0	-0.53	154	154
E2/ER alpha (dimer)/PELP1/Src	-0.13	0.18	-10000	0	-0.4	155	155
ruffle organization	-0.041	0.12	-10000	0	-0.29	41	41
ROCK2	-0.051	0.13	-10000	0	-0.37	29	29
GNA14	-0.079	0.18	-10000	0	-0.35	140	140
GNA15	0.002	0.076	-10000	0	-0.34	23	23
GNA13	0.011	0.055	-10000	0	-0.36	10	10
MMP9	-0.095	0.18	-10000	0	-0.44	48	48
MMP2	-0.09	0.2	-10000	0	-0.45	59	59

×

TCGA08_retinoblastoma

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
CDKN2B	-0.017	0.12	-10000	0	-0.38	46	46
CDKN2C	0.005	0.085	-10000	0	-0.37	23	23
CDKN2A	-0.052	0.15	-10000	0	-0.32	106	106
CCND2	0.019	0.085	0.2	74	-0.15	6	80
RB1	-0.022	0.092	0.15	3	-0.22	77	80
CDK4	0.026	0.096	0.23	77	-10000	0	77
CDK6	0.019	0.093	0.23	63	-0.2	6	69
G1/S progression	0.022	0.092	0.22	77	-0.15	3	80

×

FAS signaling pathway (CD95)

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
SPTAN1	0.067	0.099	0.24	122	-10000	0	122
RFC1	0.067	0.099	0.23	128	-10000	0	128
PRKDC	0.064	0.1	0.24	121	-0.3	1	122
RIPK1	0.018	0.024	-10000	0	-0.52	1	1
CASP7	-0.013	0.12	0.24	2	-0.68	14	16
FASLG/FAS/FADD/FAF1	-0.012	0.13	0.22	49	-0.3	47	96
MAP2K4	-0.045	0.16	-10000	0	-0.42	45	45
mol:ceramide	-0.044	0.15	-10000	0	-0.38	59	59
GSN	0.056	0.11	0.24	123	-0.3	11	134
FASLG/FAS/FADD/FAF1/Caspase 8	-0.013	0.13	-10000	0	-0.36	41	41
FAS	-0.026	0.13	-10000	0	-0.42	51	51
BID	0.012	0.066	0.29	16	-0.32	8	24
MAP3K1	-0.016	0.13	0.26	2	-0.38	29	31
MAP3K7	0.015	0.021	-10000	0	-0.25	3	3
RB1	0.054	0.11	0.23	117	-0.29	9	126
CFLAR	0.01	0.065	-10000	0	-0.44	10	10
HGF/MET	-0.036	0.14	-10000	0	-0.33	90	90
ARHGDIB	0.044	0.12	0.23	111	-0.29	20	131
FADD	-0.003	0.068	-10000	0	-0.26	35	35
actin filament polymerization	-0.056	0.11	0.3	11	-0.23	123	134
NFKB1	-0.042	0.08	-10000	0	-0.85	1	1
MAPK8	-0.06	0.19	-10000	0	-0.47	71	71
DFFA	0.066	0.099	0.24	122	-10000	0	122
DNA fragmentation during apoptosis	0.066	0.098	0.23	127	-10000	0	127
FAS/FADD/MET	-0.014	0.1	-10000	0	-0.33	39	39
CFLAR/RIP1	0.02	0.05	-10000	0	-0.36	8	8
FAIM3	-0.001	0.099	-10000	0	-0.49	20	20
FAF1	0.013	0.025	-10000	0	-0.52	1	1
PARP1	0.064	0.1	0.24	122	-0.28	5	127
DFFB	0.066	0.099	0.24	125	-10000	0	125
CHUK	-0.025	0.091	-10000	0	-0.43	6	6
FASLG	-0.065	0.17	-10000	0	-0.38	106	106
FAS/FADD	-0.02	0.11	-10000	0	-0.38	33	33
HGF	0.008	0.069	-10000	0	-0.45	11	11
LMNA	0.06	0.095	0.22	112	-0.26	8	120
CASP6	0.063	0.1	0.23	126	-0.27	4	130
CASP10	0.012	0.029	-10000	0	-0.25	6	6
CASP3	0.072	0.12	0.28	128	-10000	0	128
PTPN13	-0.071	0.2	-10000	0	-0.49	93	93
CASP8	0.013	0.068	0.37	18	-10000	0	18
IL6	-0.16	0.4	-10000	0	-1.2	59	59
MET	0	0.075	-10000	0	-0.29	31	31
ICAD/CAD	0.066	0.089	0.22	115	-10000	0	115
FASLG/FAS/FADD/FAF1/Caspase 10	-0.045	0.15	-10000	0	-0.38	59	59
activation of caspase activity by cytochrome c	0.012	0.066	0.29	16	-0.32	8	24
PAK2	0.067	0.099	0.24	123	-10000	0	123
BCL2	-0.11	0.22	-10000	0	-0.47	144	144

×

Glucocorticoid receptor regulatory network

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
PCK2	0.018	0.15	0.36	11	-0.84	10	21
SMARCC2	0.018	0	-10000	0	-10000	0	0
SMARCC1	0.012	0.051	-10000	0	-0.41	7	7
TBX21	-0.2	0.33	-10000	0	-0.66	151	151
SUMO2	0.014	0.022	-10000	0	-0.26	3	3
STAT1 (dimer)	-0.023	0.13	-10000	0	-0.34	66	66
FKBP4	0.012	0.055	-10000	0	-0.44	7	7
FKBP5	-0.045	0.16	-10000	0	-0.42	75	75
GR alpha/HSP90/FKBP51/HSP90	0.073	0.16	0.28	88	-0.29	37	125
PRL	-0.057	0.14	-10000	0	-0.87	3	3
cortisol/GR alpha (dimer)/TIF2	0.23	0.26	0.53	182	-0.4	2	184
RELA	-0.052	0.091	-10000	0	-0.26	20	20
FGG	0.2	0.22	0.49	133	-0.39	2	135
GR beta/TIF2	0.11	0.14	0.3	112	-0.32	14	126
IFNG	-0.41	0.43	-10000	0	-0.92	166	166
apoptosis	-0.004	0.18	0.5	6	-0.55	5	11
CREB1	0.007	0.056	-10000	0	-0.36	5	5
histone acetylation	-0.045	0.14	0.3	2	-0.33	63	65
BGLAP	-0.072	0.15	-10000	0	-0.57	11	11
GR/PKAc	0.092	0.14	0.28	82	-0.31	17	99
NF kappa B1 p50/RelA	-0.091	0.17	-10000	0	-0.4	63	63
SMARCD1	0.018	0	-10000	0	-10000	0	0
MDM2	0.099	0.1	0.24	134	-10000	0	134
GATA3	-0.093	0.23	-10000	0	-0.5	124	124
AKT1	0.006	0.059	0.21	4	-0.38	9	13
CSF2	-0.073	0.15	-10000	0	-0.71	11	11
GSK3B	0.016	0.008	-10000	0	-10000	0	0
NR1I3	0.009	0.18	0.48	6	-0.91	3	9
CSN2	0.17	0.18	0.41	121	-0.41	4	125
BRG1/BAF155/BAF170/BAF60A	0.041	0.034	-10000	0	-0.27	5	5
NFATC1	-0.004	0.12	-10000	0	-0.41	39	39
POU2F1	0.025	0.012	-10000	0	-0.22	1	1
CDKN1A	-0.035	0.28	-10000	0	-1.5	16	16
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.002	0.007	-10000	0	-10000	0	0
SFN	-0.015	0.12	-10000	0	-0.45	37	37
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.064	0.16	0.29	64	-0.3	36	100
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.086	0.33	0.5	2	-0.8	80	82
JUN	-0.21	0.24	-10000	0	-0.52	150	150
IL4	-0.1	0.2	-10000	0	-0.64	33	33
CDK5R1	0.013	0.031	-10000	0	-0.25	7	7
PRKACA	0.018	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.22	0.28	0.21	46	-0.5	217	263
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.081	0.15	0.3	65	-0.29	24	89
cortisol/GR alpha (monomer)	0.28	0.32	0.63	187	-0.46	3	190
NCOA2	0.009	0.063	-10000	0	-0.4	11	11
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.18	0.21	-10000	0	-0.47	155	155
AP-1/NFAT1-c-4	-0.44	0.4	-10000	0	-0.79	244	244
AFP	-0.16	0.2	-10000	0	-0.71	20	20
SUV420H1	0.014	0.037	-10000	0	-0.29	7	7
IRF1	0.11	0.25	0.45	51	-0.81	19	70
TP53	-0.015	0.17	-10000	0	-0.53	47	47
PPP5C	0.012	0.052	-10000	0	-0.39	8	8
KRT17	-0.53	0.58	-10000	0	-1.2	187	187
KRT14	-0.32	0.51	-10000	0	-1.3	104	104
TBP	0.028	0.012	-10000	0	-0.24	1	1
CREBBP	0.061	0.1	0.26	79	-0.53	2	81
HDAC1	0.011	0.025	-10000	0	-0.53	1	1
HDAC2	0.008	0.053	-10000	0	-0.29	14	14
AP-1	-0.44	0.4	-10000	0	-0.8	244	244
MAPK14	0.015	0.013	-10000	0	-0.25	1	1
MAPK10	-0.026	0.12	-10000	0	-0.36	58	58
MAPK11	0.016	0.008	-10000	0	-10000	0	0
KRT5	-0.54	0.58	-10000	0	-1.1	213	213
interleukin-1 receptor activity	-0.001	0.009	-10000	0	-10000	0	0
NCOA1	0.013	0.059	-10000	0	-0.52	6	6
STAT1	-0.023	0.13	-10000	0	-0.34	66	66
CGA	-0.12	0.2	-10000	0	-0.65	29	29
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.12	0.16	0.37	104	-0.39	2	106
MAPK3	0.014	0.027	-10000	0	-0.39	2	2
MAPK1	0.014	0.034	-10000	0	-0.52	2	2
ICAM1	-0.22	0.34	-10000	0	-0.8	95	95
NFKB1	-0.053	0.093	-10000	0	-0.28	18	18
MAPK8	-0.15	0.19	-10000	0	-0.42	128	128
MAPK9	-0.008	0.11	-10000	0	-0.51	24	24
cortisol/GR alpha (dimer)	-0.014	0.18	0.5	6	-0.58	5	11
BAX	0.001	0.11	-10000	0	-10000	0	0
POMC	-0.13	0.2	-10000	0	-1.2	6	6
EP300	0.059	0.11	0.26	79	-0.53	4	83
cortisol/GR alpha (dimer)/p53	0.21	0.28	0.55	158	-0.48	4	162
proteasomal ubiquitin-dependent protein catabolic process	0.07	0.08	0.21	77	-10000	0	77
SGK1	0.11	0.13	0.34	101	-0.26	4	105
IL13	-0.31	0.29	-10000	0	-0.62	198	198
IL6	-0.28	0.41	-10000	0	-0.84	138	138
PRKACG	0.016	0.033	-10000	0	-0.52	2	2
IL5	-0.26	0.24	-10000	0	-0.67	76	76
IL2	-0.32	0.33	-10000	0	-0.74	142	142
CDK5	0.015	0.027	-10000	0	-0.39	2	2
PRKACB	-0.036	0.14	-10000	0	-0.34	79	79
HSP90AA1	0.013	0.045	-10000	0	-0.39	6	6
IL8	-0.27	0.37	-10000	0	-0.85	113	113
CDK5R1/CDK5	0.02	0.03	-10000	0	-0.37	1	1
NF kappa B1 p50/RelA/PKAc	-0.063	0.15	-10000	0	-0.36	56	56
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.23	0.24	0.51	180	-0.36	1	181
SMARCA4	0.015	0.031	-10000	0	-0.32	4	4
chromatin remodeling	0.16	0.16	0.36	141	-0.33	1	142
NF kappa B1 p50/RelA/Cbp	-0.018	0.16	0.31	28	-0.39	26	54
JUN (dimer)	-0.21	0.24	-10000	0	-0.52	150	150
YWHAH	0.013	0.048	-10000	0	-0.47	5	5
VIPR1	-0.11	0.24	-10000	0	-0.68	55	55
NR3C1	0.16	0.21	0.42	145	-0.46	11	156
NR4A1	0.01	0.063	-10000	0	-0.44	4	4
TIF2/SUV420H1	0.017	0.055	-10000	0	-0.42	6	6
MAPKKK cascade	-0.004	0.18	0.5	6	-0.55	5	11
cortisol/GR alpha (dimer)/Src-1	0.24	0.26	0.54	175	-0.43	3	178
PBX1	0.004	0.1	-10000	0	-0.49	22	22
POU1F1	0.023	0.033	-10000	0	-0.3	5	5
SELE	-0.35	0.47	-10000	0	-1	155	155
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.16	0.16	0.36	141	-0.34	1	142
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.23	0.24	0.51	180	-0.36	1	181
mol:cortisol	0.16	0.19	0.37	185	-10000	0	185
MMP1	-0.44	0.52	-10000	0	-0.99	201	201

×

Noncanonical Wnt signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.013	0.048	-9999	-0.47	5	5
GNB1/GNG2	-0.11	0.19	-9999	-0.42	103	103
mol:DAG	-0.093	0.18	-9999	-0.44	72	72
PLCG1	-0.096	0.18	-9999	-0.46	72	72
YES1	-0.12	0.2	-9999	-0.45	105	105
FZD3	-0.03	0.15	-9999	-0.48	51	51
FZD6	-0.077	0.2	-9999	-0.45	108	108
G protein	-0.099	0.19	-9999	-0.46	76	76
MAP3K7	-0.068	0.15	-9999	-0.4	58	58
mol:Ca2+	-0.09	0.17	-9999	-0.43	72	72
mol:IP3	-0.093	0.18	-9999	-0.44	72	72
NLK	0.016	0.044	-9999	-0.9	1	1
GNB1	0.013	0.052	-9999	-0.52	5	5
CAMK2A	-0.079	0.16	-9999	-0.42	61	61
MAP3K7IP1	0.018	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.13	0.21	-9999	-0.34	214	214
CSNK1A1	0.017	0.023	-9999	-0.52	1	1
GNAS	-0.12	0.2	-9999	-0.44	105	105
GO:0007205	-0.092	0.17	-9999	-0.43	73	73
WNT6	-0.011	0.087	-9999	-0.26	54	54
WNT4	-0.062	0.18	-9999	-0.45	90	90
NFAT1/CK1 alpha	-0.091	0.19	-9999	-0.46	75	75
GNG2	0.016	0.029	-9999	-0.34	3	3
WNT5A	-0.084	0.2	-9999	-0.43	120	120
WNT11	-0.013	0.089	-9999	-0.26	57	57
CDC42	-0.11	0.2	-9999	-0.42	104	104

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.33	0.63	-10000	0	-1.3	115	115
STAT6 (cleaved dimer)	-0.43	0.56	-10000	0	-1.2	144	144
IGHG1	-0.083	0.25	-10000	0	-0.45	60	60
IGHG3	-0.33	0.6	-10000	0	-1.2	139	139
AKT1	-0.11	0.31	-10000	0	-0.68	49	49
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.065	0.24	-10000	0	-0.6	28	28
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.14	0.34	-10000	0	-0.75	60	60
THY1	-0.35	0.65	-10000	0	-1.4	118	118
MYB	-0.097	0.22	-10000	0	-0.49	119	119
HMGA1	0.014	0.039	-10000	0	-0.36	5	5
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.14	0.34	-10000	0	-0.65	91	91
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.12	0.31	-10000	0	-0.75	34	34
SP1	0.021	0.03	-10000	0	-0.53	1	1
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.016	0.055	-10000	0	-0.4	7	7
STAT6 (dimer)/ETS1	-0.34	0.63	-10000	0	-1.3	135	135
SOCS1	-0.18	0.4	-10000	0	-0.78	103	103
SOCS3	-0.12	0.33	-10000	0	-0.95	24	24
FCER2	-0.22	0.46	-10000	0	-0.94	88	88
PARP14	0.006	0.078	-10000	0	-0.43	15	15
CCL17	-0.42	0.71	-10000	0	-1.4	146	146
GRB2	0.016	0.024	-10000	0	-0.25	4	4
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.083	0.26	-10000	0	-0.64	25	25
T cell proliferation	-0.35	0.65	-10000	0	-1.3	127	127
IL4R/JAK1	-0.35	0.64	-10000	0	-1.3	131	131
EGR2	-0.39	0.69	-10000	0	-1.4	134	134
JAK2	0.001	0.072	-10000	0	-0.34	12	12
JAK3	0.021	0.008	-10000	0	-10000	0	0
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
JAK1	0.012	0.061	-10000	0	-0.52	6	6
COL1A2	-0.22	0.54	-10000	0	-1.5	72	72
CCL26	-0.34	0.63	-10000	0	-1.3	124	124
IL4R	-0.37	0.7	-10000	0	-1.4	123	123
PTPN6	0.021	0.038	-10000	0	-0.42	3	3
IL13RA2	-0.38	0.67	-10000	0	-1.3	140	140
IL13RA1	-0.002	0.089	-10000	0	-0.49	12	12
IRF4	-0.038	0.2	-10000	0	-0.99	6	6
ARG1	-0.064	0.27	-10000	0	-1	21	21
CBL	-0.13	0.32	-10000	0	-0.61	88	88
GTF3A	0.02	0.032	-10000	0	-0.38	2	2
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
IL13RA1/JAK2	0.003	0.099	-10000	0	-0.36	18	18
IRF4/BCL6	-0.044	0.19	-10000	0	-0.92	6	6
CD40LG	0.012	0.07	-10000	0	-0.32	20	20
MAPK14	-0.13	0.33	-10000	0	-0.67	67	67
mitosis	-0.1	0.3	-10000	0	-0.65	47	47
STAT6	-0.43	0.85	-10000	0	-1.6	139	139
SPI1	0.012	0.07	-10000	0	-0.43	11	11
RPS6KB1	-0.099	0.29	-10000	0	-0.64	40	40
STAT6 (dimer)	-0.44	0.86	-10000	0	-1.6	139	139
STAT6 (dimer)/PARP14	-0.39	0.7	-10000	0	-1.4	140	140
mast cell activation	0.004	0.019	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.11	0.3	-10000	0	-0.68	47	47
FRAP1	-0.11	0.31	-10000	0	-0.68	49	49
LTA	-0.33	0.63	-10000	0	-1.3	119	119
FES	0.01	0.058	-10000	0	-0.39	10	10
T-helper 1 cell differentiation	0.39	0.75	1.4	139	-10000	0	139
CCL11	-0.38	0.65	-10000	0	-1.3	141	141
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.1	0.3	-10000	0	-0.68	35	35
IL2RG	0.001	0.08	-10000	0	-0.29	35	35
IL10	-0.34	0.63	-10000	0	-1.3	120	120
IRS1	-0.048	0.17	-10000	0	-0.49	68	68
IRS2	-0.026	0.13	-10000	0	-0.39	57	57
IL4	-0.039	0.22	-10000	0	-1.4	6	6
IL5	-0.34	0.63	-10000	0	-1.3	116	116
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.24	0.5	-10000	0	-0.95	124	124
COL1A1	-0.23	0.56	-10000	0	-1.6	72	72
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.37	0.67	-10000	0	-1.4	120	120
IL2R gamma/JAK3	0.017	0.059	-10000	0	-0.33	5	5
TFF3	-0.52	0.77	-10000	0	-1.4	191	191
ALOX15	-0.35	0.64	-10000	0	-1.4	111	111
MYBL1	-0.066	0.17	-10000	0	-0.36	117	117
T-helper 2 cell differentiation	-0.25	0.49	-10000	0	-0.96	125	125
SHC1	0.017	0.023	-10000	0	-0.52	1	1
CEBPB	0.008	0.075	-10000	0	-0.34	20	20
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.12	0.32	-10000	0	-0.73	44	44
mol:PI-3-4-5-P3	-0.11	0.31	-10000	0	-0.68	49	49
PI3K	-0.12	0.33	-10000	0	-0.72	49	49
DOK2	-0.021	0.13	-10000	0	-0.4	48	48
ETS1	0.007	0.07	-10000	0	-0.28	24	24
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.073	0.25	-10000	0	-0.62	23	23
ITGB3	-0.34	0.63	-10000	0	-1.3	121	121
PIGR	-0.5	0.76	-10000	0	-1.4	180	180
IGHE	0.022	0.086	0.21	45	-0.25	4	49
MAPKKK cascade	-0.071	0.24	-10000	0	-0.6	23	23
BCL6	-0.004	0.1	-10000	0	-0.46	24	24
OPRM1	-0.34	0.63	-10000	0	-1.3	116	116
RETNLB	-0.33	0.63	-10000	0	-1.3	118	118
SELP	-0.46	0.75	-10000	0	-1.5	158	158
AICDA	-0.35	0.61	-10000	0	-1.3	129	129

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.007	0.074	-9999	-0.5	11	11
LAT2	-0.089	0.18	-9999	-0.34	142	142
AP1	-0.14	0.22	-9999	-0.49	125	125
mol:PIP3	-0.099	0.22	-9999	-0.49	92	92
IKBKB	-0.043	0.12	-9999	-0.26	86	86
AKT1	-0.068	0.16	-9999	-0.4	74	74
IKBKG	-0.041	0.12	-9999	-0.26	86	86
MS4A2	-0.15	0.23	-9999	-0.43	203	203
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.015	0.029	-9999	-0.34	3	3
MAP3K1	-0.086	0.19	-9999	-0.43	97	97
mol:Ca2+	-0.071	0.16	-9999	-0.36	92	92
LYN	0.012	0.032	-9999	-0.26	7	7
CBLB	-0.086	0.18	-9999	-0.34	139	139
SHC1	0.017	0.023	-9999	-0.52	1	1
RasGAP/p62DOK	-0.013	0.11	-9999	-0.3	58	58
positive regulation of cell migration	-0.013	0.089	-9999	-0.28	46	46
INPP5D	0	0	-9999	-10000	0	0
PLD2	-0.088	0.18	-9999	-0.38	103	103
PTPN13	-0.12	0.22	-9999	-0.55	78	78
PTPN11	0.012	0.027	-9999	-0.56	1	1
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.046	0.14	-9999	-0.32	74	74
SYK	-0.025	0.14	-9999	-0.49	43	43
GRB2	0.015	0.024	-9999	-0.26	4	4
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.2	-9999	-0.49	100	100
LAT	-0.092	0.18	-9999	-0.42	91	91
PAK2	-0.081	0.2	-9999	-0.44	92	92
NFATC2	-0.042	0.082	-9999	-0.62	5	5
HRAS	-0.096	0.21	-9999	-0.48	95	95
GAB2	0.009	0.048	-9999	-0.25	17	17
PLA2G1B	0.038	0.026	-9999	-10000	0	0
Fc epsilon R1	-0.12	0.2	-9999	-0.39	168	168
Antigen/IgE/Fc epsilon R1	-0.11	0.19	-9999	-0.35	168	168
mol:GDP	-0.11	0.22	-9999	-0.51	95	95
JUN	-0.034	0.15	-9999	-0.46	57	57
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	-0.01	0.11	-9999	-0.42	33	33
FOS	-0.11	0.2	-9999	-0.37	171	171
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.097	0.18	-9999	-0.36	139	139
CHUK	-0.046	0.12	-9999	-0.26	91	91
KLRG1	-0.084	0.17	-9999	-0.39	87	87
VAV1	-0.1	0.2	-9999	-0.36	149	149
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.086	0.18	-9999	-0.34	139	139
negative regulation of mast cell degranulation	-0.079	0.16	-9999	-0.36	87	87
BTK	-0.11	0.23	-9999	-0.52	93	93
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.13	0.25	-9999	-0.5	122	122
GAB2/PI3K/SHP2	-0.1	0.15	-9999	-0.43	76	76
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.097	0.2	-9999	-0.44	96	96
RAF1	0.029	0.026	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.12	0.21	-9999	-0.36	184	184
FCER1G	0.02	0.026	-9999	-0.26	4	4
FCER1A	-0.074	0.2	-9999	-0.51	91	91
Antigen/IgE/Fc epsilon R1/Fyn	-0.095	0.18	-9999	-0.33	170	170
MAPK3	0.037	0.026	-9999	-10000	0	0
MAPK1	0.037	0.026	-9999	-10000	0	0
NFKB1	0.017	0.023	-9999	-0.52	1	1
MAPK8	-0.02	0.11	-9999	-0.48	19	19
DUSP1	-0.038	0.15	-9999	-0.41	69	69
NF-kappa-B/RelA	-0.039	0.061	-9999	-0.18	33	33
actin cytoskeleton reorganization	-0.088	0.18	-9999	-0.48	65	65
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.091	0.2	-9999	-0.45	97	97
FER	-0.086	0.18	-9999	-0.34	140	140
RELA	0.018	0	-9999	-10000	0	0
ITK	-0.053	0.13	-9999	-0.4	52	52
SOS1	0.017	0.023	-9999	-0.52	1	1
PLCG1	-0.1	0.22	-9999	-0.51	93	93
cytokine secretion	-0.029	0.044	-9999	-0.17	3	3
SPHK1	-0.11	0.2	-9999	-0.35	166	166
PTK2	-0.092	0.19	-9999	-0.5	65	65
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.21	-9999	-0.51	96	96
EDG1	-0.013	0.089	-9999	-0.28	46	46
mol:DAG	-0.095	0.22	-9999	-0.48	98	98
MAP2K2	0.032	0.031	-9999	-0.26	2	2
MAP2K1	0.033	0.024	-9999	-10000	0	0
MAP2K7	0.017	0.023	-9999	-0.52	1	1
KLRG1/SHP2	-0.073	0.15	-9999	-0.37	77	77
MAP2K4	-0.011	0.16	-9999	-0.91	16	16
Fc epsilon R1/FcgammaRIIB	-0.12	0.22	-9999	-0.38	184	184
mol:Choline	-0.087	0.17	-9999	-0.38	103	103
SHC/Grb2/SOS1	-0.066	0.17	-9999	-0.41	73	73
FYN	0.008	0.067	-9999	-0.41	12	12
DOK1	0.002	0.083	-9999	-0.41	19	19
PXN	-0.079	0.18	-9999	-0.46	65	65
HCLS1	-0.096	0.19	-9999	-0.36	145	145
PRKCB	-0.069	0.16	-9999	-0.35	99	99
FCGR2B	-0.031	0.15	-9999	-0.5	50	50
IGHE	-0.003	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.08	0.16	-9999	-0.37	87	87
LCP2	-0.004	0.098	-9999	-0.4	27	27
PLA2G4A	-0.11	0.21	-9999	-0.38	157	157
RASA1	0.004	0.078	-9999	-0.42	16	16
mol:Phosphatidic acid	-0.087	0.17	-9999	-0.38	103	103
IKK complex	-0.023	0.098	-9999	-0.2	70	70
WIPF1	0.005	0.076	-9999	-0.4	16	16

×

IL27-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
TGFB1	0.026	0.03	-10000	0	-0.46	2	2
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.17	0.26	0.61	102	-10000	0	102
IL27/IL27R/JAK1	-0.2	0.35	-10000	0	-0.91	75	75
TBX21	-0.22	0.3	-10000	0	-0.6	163	163
IL12B	0.001	0.075	-10000	0	-0.35	21	21
IL12A	-0.01	0.064	-10000	0	-0.19	55	55
IL6ST	-0.12	0.22	-10000	0	-0.47	143	143
IL27RA/JAK1	-0.11	0.33	-10000	0	-1.2	39	39
IL27	-0.082	0.2	-10000	0	-0.5	98	98
TYK2	0.011	0.011	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.006	0.11	-10000	0	-1.4	1	1
T-helper 2 cell differentiation	0.17	0.26	0.61	102	-10000	0	102
T cell proliferation during immune response	0.17	0.26	0.61	102	-10000	0	102
MAPKKK cascade	-0.17	0.26	-10000	0	-0.61	102	102
STAT3	0.015	0.04	-10000	0	-0.52	3	3
STAT2	0.018	0	-10000	0	-10000	0	0
STAT1	-0.021	0.12	-10000	0	-0.33	58	58
IL12RB1	0.017	0.003	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.21	0.28	-10000	0	-0.58	158	158
IL27/IL27R/JAK2/TYK2	-0.17	0.27	-10000	0	-0.62	102	102
positive regulation of T cell mediated cytotoxicity	-0.17	0.26	-10000	0	-0.61	102	102
STAT1 (dimer)	-0.27	0.4	0.46	9	-0.91	104	113
JAK2	0.004	0.055	-10000	0	-0.33	12	12
JAK1	0.011	0.057	-10000	0	-0.52	6	6
STAT2 (dimer)	-0.16	0.25	-10000	0	-0.59	101	101
T cell proliferation	-0.2	0.27	-10000	0	-0.61	118	118
IL12/IL12R/TYK2/JAK2	-0.033	0.15	-10000	0	-0.9	8	8
IL17A	-0.006	0.11	-10000	0	-1.4	1	1
mast cell activation	0.17	0.26	0.61	102	-10000	0	102
IFNG	-0.031	0.047	-10000	0	-0.11	90	90
T cell differentiation	-0.01	0.009	0.024	1	-0.023	140	141
STAT3 (dimer)	-0.16	0.25	-10000	0	-0.6	96	96
STAT5A (dimer)	-0.16	0.26	-10000	0	-0.61	98	98
STAT4 (dimer)	-0.17	0.27	-10000	0	-0.6	114	114
STAT4	-0.024	0.13	-10000	0	-0.42	50	50
T cell activation	0.002	0.038	0.097	58	-10000	0	58
IL27R/JAK2/TYK2	-0.16	0.33	-10000	0	-0.98	57	57
GATA3	-0.25	0.55	-10000	0	-1.3	119	119
IL18	-0.035	0.12	-10000	0	-0.32	76	76
positive regulation of mast cell cytokine production	-0.15	0.25	-10000	0	-0.59	97	97
IL27/EBI3	-0.06	0.16	-10000	0	-0.38	95	95
IL27RA	-0.12	0.34	-10000	0	-1.3	38	38
IL6	-0.077	0.18	-10000	0	-0.35	147	147
STAT5A	0.011	0.056	-10000	0	-0.42	8	8
monocyte differentiation	-0.001	0.002	-10000	0	-10000	0	0
IL2	0.054	0.16	0.49	38	-1.2	3	41
IL1B	-0.033	0.12	-10000	0	-0.29	81	81
EBI3	0.002	0.071	-10000	0	-0.44	12	12
TNF	-0.003	0.067	-10000	0	-0.25	31	31

×

IL6-mediated signaling events

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
BCL2L1	-0.11	0.3	-10000	0	-0.75	46	46
CRP	-0.11	0.3	-10000	0	-0.76	44	44
cell cycle arrest	-0.14	0.34	-10000	0	-0.78	80	80
TIMP1	-0.11	0.3	-10000	0	-0.76	60	60
IL6ST	-0.11	0.22	-10000	0	-0.46	143	143
Rac1/GDP	-0.1	0.22	0.28	2	-0.45	112	114
AP1	-0.05	0.16	-10000	0	-0.43	39	39
GAB2	0.011	0.048	-10000	0	-0.25	17	17
TNFSF11	-0.18	0.41	-10000	0	-0.97	89	89
HSP90B1	0.008	0.11	-10000	0	-0.8	6	6
GAB1	0.007	0.074	-10000	0	-0.42	14	14
MAPK14	-0.11	0.22	-10000	0	-0.52	74	74
AKT1	0.038	0.073	-10000	0	-0.47	3	3
FOXO1	0.036	0.086	-10000	0	-0.45	5	5
MAP2K6	-0.12	0.22	0.27	2	-0.41	144	146
mol:GTP	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.1	0.25	-10000	0	-0.53	92	92
MITF	-0.11	0.22	0.29	2	-0.43	124	126
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.018	0	-10000	0	-10000	0	0
A2M	-0.042	0.28	-10000	0	-1.4	22	22
CEBPB	0.013	0.073	-10000	0	-0.33	20	20
GRB2/SOS1/GAB family/SHP2	-0.017	0.1	-10000	0	-0.39	10	10
STAT3	-0.15	0.37	-10000	0	-0.84	80	80
STAT1	-0.042	0.17	-10000	0	-0.95	16	16
CEBPD	-0.16	0.38	-10000	0	-0.94	75	75
PIK3CA	0.017	0.029	-10000	0	-0.34	3	3
PI3K	0.008	0.083	-10000	0	-0.37	21	21
JUN	-0.034	0.15	-10000	0	-0.46	57	57
PIAS3/MITF	-0.095	0.21	0.27	2	-0.41	115	117
MAPK11	-0.11	0.22	-10000	0	-0.51	77	77
STAT3 (dimer)/FOXO1	-0.082	0.29	-10000	0	-0.64	68	68
GRB2/SOS1/GAB family	-0.11	0.18	-10000	0	-0.46	75	75
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.12	0.22	-10000	0	-0.39	167	167
GRB2	0.017	0.024	-10000	0	-0.25	4	4
JAK2	0.01	0.053	-10000	0	-0.32	12	12
LBP	-0.097	0.26	-10000	0	-0.62	50	50
PIK3R1	-0.008	0.11	-10000	0	-0.42	33	33
JAK1	0.013	0.059	-10000	0	-0.53	6	6
MYC	-0.14	0.37	-10000	0	-0.93	67	67
FGG	-0.11	0.3	-10000	0	-0.76	47	47
macrophage differentiation	-0.14	0.34	-10000	0	-0.78	80	80
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.13	0.2	-10000	0	-0.35	204	204
JUNB	-0.11	0.29	-10000	0	-0.73	50	50
FOS	-0.11	0.2	-10000	0	-0.37	171	171
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.12	0.22	0.31	2	-0.42	144	146
STAT1/PIAS1	-0.11	0.22	0.32	2	-0.44	118	120
GRB2/SOS1/GAB family/SHP2/PI3K	0.03	0.067	-10000	0	-0.38	4	4
STAT3 (dimer)	-0.14	0.36	-10000	0	-0.83	79	79
PRKCD	-0.1	0.27	-10000	0	-0.59	81	81
IL6R	0.002	0.085	-10000	0	-0.37	23	23
SOCS3	-0.1	0.23	-10000	0	-0.69	39	39
gp130 (dimer)/JAK1/JAK1/LMO4	-0.096	0.19	-10000	0	-0.35	170	170
Rac1/GTP	-0.11	0.24	-10000	0	-0.47	109	109
HCK	-0.005	0.11	-10000	0	-0.47	25	25
MAPKKK cascade	0.008	0.093	-10000	0	-0.55	4	4
bone resorption	-0.16	0.38	-10000	0	-0.88	90	90
IRF1	-0.12	0.33	-10000	0	-0.82	61	61
mol:GDP	-0.12	0.23	0.29	2	-0.44	133	135
SOS1	0.018	0.024	-10000	0	-0.52	1	1
VAV1	-0.12	0.23	0.29	2	-0.44	133	135
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.11	0.22	-10000	0	-0.46	102	102
PTPN11	0.004	0.058	-10000	0	-1.2	1	1
IL6/IL6RA	-0.056	0.14	-10000	0	-0.36	77	77
gp130 (dimer)/TYK2/TYK2/LMO4	-0.095	0.18	-10000	0	-0.34	169	169
gp130 (dimer)/JAK2/JAK2/LMO4	-0.099	0.18	-10000	0	-0.35	174	174
IL6	-0.084	0.18	-10000	0	-0.36	146	146
PIAS3	0.018	0	-10000	0	-10000	0	0
PTPRE	-0.002	0.088	-10000	0	-0.47	17	17
PIAS1	0.017	0.012	-10000	0	-0.25	1	1
RAC1	0.018	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.11	0.18	0.27	2	-0.35	150	152
LMO4	-0.073	0.18	-10000	0	-0.38	123	123
STAT3 (dimer)/PIAS3	-0.14	0.34	-10000	0	-0.77	80	80
MCL1	0.043	0.083	-10000	0	-0.82	2	2

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.058	0.21	-10000	0	-0.46	93	93
FYN	-0.085	0.26	-10000	0	-0.56	101	101
LAT/GRAP2/SLP76	-0.098	0.21	-10000	0	-0.48	103	103
IKBKB	0.012	0.047	-10000	0	-0.31	10	10
AKT1	-0.048	0.19	-10000	0	-0.38	104	104
B2M	-0.005	0.1	-10000	0	-0.45	25	25
IKBKG	0.003	0.061	-10000	0	-0.14	39	39
MAP3K8	-0.036	0.15	-10000	0	-0.39	70	70
mol:Ca2+	-0.022	0.031	-10000	0	-0.084	64	64
integrin-mediated signaling pathway	0.007	0.068	-10000	0	-0.31	20	20
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.083	0.26	-10000	0	-0.56	105	105
TRPV6	-0.11	0.19	-10000	0	-0.38	159	159
CD28	-0.044	0.16	-10000	0	-0.4	78	78
SHC1	-0.09	0.26	-10000	0	-0.56	102	102
receptor internalization	-0.12	0.3	-10000	0	-0.62	114	114
PRF1	-0.079	0.24	-10000	0	-0.74	38	38
KRAS	0.009	0.065	-10000	0	-0.44	10	10
GRB2	0.016	0.024	-10000	0	-0.25	4	4
COT/AKT1	-0.047	0.16	-10000	0	-0.33	96	96
LAT	-0.095	0.27	-10000	0	-0.56	112	112
EntrezGene:6955	0	0.004	-10000	0	-10000	0	0
CD3D	-0.029	0.13	-10000	0	-0.35	68	68
CD3E	0.016	0.018	-10000	0	-0.26	2	2
CD3G	-0.092	0.2	-10000	0	-0.41	136	136
RASGRP2	-0.002	0.036	-10000	0	-0.17	13	13
RASGRP1	-0.061	0.2	-10000	0	-0.4	106	106
HLA-A	-0.012	0.12	-10000	0	-0.43	34	34
RASSF5	-0.004	0.096	-10000	0	-0.38	29	29
RAP1A/GTP/RAPL	0.007	0.068	-10000	0	-0.31	20	20
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.004	0.064	-10000	0	-0.12	62	62
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.045	0.078	-10000	0	-0.21	72	72
PRKCA	-0.043	0.1	-10000	0	-0.25	87	87
GRAP2	0.012	0.042	-10000	0	-0.28	10	10
mol:IP3	-0.051	0.18	0.22	43	-0.38	95	138
EntrezGene:6957	-0.001	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.08	0.22	-10000	0	-0.46	97	97
ORAI1	0.07	0.11	0.3	66	-0.38	1	67
CSK	-0.088	0.26	-10000	0	-0.56	99	99
B7 family/CD28	-0.11	0.3	-10000	0	-0.61	113	113
CHUK	0.005	0.081	-10000	0	-0.5	13	13
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.11	0.3	-10000	0	-0.65	103	103
PTPN6	-0.094	0.26	-10000	0	-0.57	101	101
VAV1	-0.1	0.28	-10000	0	-0.59	107	107
Monovalent TCR/CD3	-0.096	0.22	-10000	0	-0.4	144	144
CBL	0.017	0.012	-10000	0	-0.25	1	1
LCK	-0.097	0.28	-10000	0	-0.61	98	98
PAG1	-0.092	0.26	-10000	0	-0.58	99	99
RAP1A	0.012	0.057	-10000	0	-0.52	6	6
TCR/CD3/MHC I/CD8/LCK	-0.12	0.3	-10000	0	-0.66	102	102
CD80	0.009	0.048	-10000	0	-0.27	14	14
CD86	-0.008	0.11	-10000	0	-0.5	26	26
PDK1/CARD11/BCL10/MALT1	-0.054	0.094	-10000	0	-0.24	89	89
HRAS	0.012	0.051	-10000	0	-0.41	7	7
GO:0035030	-0.091	0.24	-10000	0	-0.5	113	113
CD8A	0	0.005	-10000	0	-10000	0	0
CD8B	0.001	0.069	-10000	0	-0.28	29	29
PTPRC	-0.041	0.16	-10000	0	-0.42	71	71
PDK1/PKC theta	-0.06	0.23	-10000	0	-0.48	103	103
CSK/PAG1	-0.08	0.25	-10000	0	-0.54	97	97
SOS1	0.017	0.023	-10000	0	-0.52	1	1
peptide-MHC class I	-0.01	0.13	-10000	0	-0.48	31	31
GRAP2/SLP76	-0.085	0.26	-10000	0	-0.56	100	100
STIM1	0.034	0.059	-10000	0	-0.36	2	2
RAS family/GTP	-0.002	0.088	-10000	0	-0.17	67	67
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.13	0.33	-10000	0	-0.67	114	114
mol:DAG	-0.072	0.14	0.13	1	-0.34	99	100
RAP1A/GDP	0.003	0.031	-10000	0	-0.079	19	19
PLCG1	0.016	0.026	-10000	0	-0.39	2	2
CD247	-0.11	0.21	-10000	0	-0.41	153	153
cytotoxic T cell degranulation	-0.076	0.23	-10000	0	-0.7	39	39
RAP1A/GTP	-0.005	0.014	-10000	0	-0.075	17	17
mol:PI-3-4-5-P3	-0.063	0.22	-10000	0	-0.46	105	105
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.076	0.23	0.24	38	-0.49	99	137
NRAS	0.005	0.076	-10000	0	-0.4	16	16
ZAP70	0.005	0.06	-10000	0	-0.27	24	24
GRB2/SOS1	0.024	0.023	-10000	0	-0.37	1	1
LAT/GRAP2/SLP76/VAV1	-0.1	0.21	0.16	1	-0.49	103	104
MALT1	0.011	0.053	-10000	0	-0.37	9	9
TRAF6	0.017	0.023	-10000	0	-0.52	1	1
CD8 heterodimer	0.002	0.049	-10000	0	-0.19	29	29
CARD11	0.002	0.077	-10000	0	-0.33	24	24
PRKCB	-0.048	0.1	-10000	0	-0.24	99	99
PRKCE	-0.045	0.11	-10000	0	-0.25	91	91
PRKCQ	-0.078	0.26	-10000	0	-0.54	105	105
LCP2	-0.004	0.097	-10000	0	-0.4	27	27
BCL10	0.017	0.012	-10000	0	-0.25	1	1
regulation of survival gene product expression	-0.037	0.16	-10000	0	-0.33	103	103
IKK complex	0.012	0.059	-10000	0	-0.1	47	47
RAS family/GDP	-0.008	0.015	-10000	0	-0.064	20	20
MAP3K14	-0.029	0.12	-10000	0	-0.26	87	87
PDPK1	-0.042	0.18	-10000	0	-0.36	102	102
TCR/CD3/MHC I/CD8/Fyn	-0.091	0.26	-10000	0	-0.6	89	89

×

IL12-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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.029	0.12	-10000	0	-0.35	30	30
TBX21	-0.3	0.59	-10000	0	-1.3	126	126
B2M	-0.005	0.1	-10000	0	-0.45	25	25
TYK2	0.012	0.022	-10000	0	-10000	0	0
IL12RB1	0.012	0.022	-10000	0	-10000	0	0
GADD45B	-0.18	0.44	-10000	0	-1.1	85	85
IL12RB2	-0.076	0.16	-10000	0	-0.32	142	142
GADD45G	-0.18	0.43	-10000	0	-1	86	86
natural killer cell activation	-0.005	0.024	-10000	0	-10000	0	0
RELB	0.003	0.078	-10000	0	-0.38	19	19
RELA	0.018	0	-10000	0	-10000	0	0
IL18	-0.046	0.17	-10000	0	-0.44	76	76
IL2RA	-0.03	0.14	-10000	0	-0.4	60	60
IFNG	-0.088	0.17	-10000	0	-0.33	161	161
STAT3 (dimer)	-0.14	0.37	-10000	0	-0.77	111	111
HLA-DRB5	-0.002	0.093	-10000	0	-0.51	17	17
FASLG	-0.24	0.52	-10000	0	-1.1	107	107
NF kappa B2 p52/RelB	-0.24	0.41	-10000	0	-0.88	127	127
CD4	0.015	0.007	-10000	0	-10000	0	0
SOCS1	0.015	0.031	-10000	0	-0.32	4	4
EntrezGene:6955	-0.005	0.012	-10000	0	-10000	0	0
CD3D	-0.033	0.13	-10000	0	-0.35	68	68
CD3E	0.013	0.021	-10000	0	-0.28	2	2
CD3G	-0.097	0.2	-10000	0	-0.42	136	136
IL12Rbeta2/JAK2	-0.048	0.13	-10000	0	-0.3	80	80
CCL3	-0.2	0.44	-10000	0	-1	96	96
CCL4	-0.2	0.46	-10000	0	-1	101	101
HLA-A	-0.012	0.11	-10000	0	-0.43	34	34
IL18/IL18R	-0.056	0.21	-10000	0	-0.41	117	117
NOS2	-0.19	0.44	-10000	0	-0.86	124	124
IL12/IL12R/TYK2/JAK2/SPHK2	-0.029	0.12	-10000	0	-0.37	28	28
IL1R1	-0.25	0.51	-10000	0	-1.1	117	117
IL4	0.016	0.063	-10000	0	-0.48	7	7
JAK2	0.004	0.06	-10000	0	-0.34	12	12
EntrezGene:6957	-0.004	0.011	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.13	0.33	-10000	0	-0.81	71	71
RAB7A	-0.12	0.34	-10000	0	-0.81	79	79
lysosomal transport	-0.12	0.33	-10000	0	-0.76	80	80
FOS	-0.29	0.5	-10000	0	-1.1	121	121
STAT4 (dimer)	-0.18	0.43	-10000	0	-0.9	114	114
STAT5A (dimer)	-0.27	0.42	-10000	0	-0.91	130	130
GZMA	-0.2	0.43	-10000	0	-0.87	126	126
GZMB	-0.28	0.57	-10000	0	-1.2	120	120
HLX	0.005	0.079	-10000	0	-0.48	13	13
LCK	-0.25	0.52	-10000	0	-1	135	135
TCR/CD3/MHC II/CD4	-0.11	0.23	-10000	0	-0.5	106	106
IL2/IL2R	-0.014	0.14	-10000	0	-0.33	71	71
MAPK14	-0.18	0.44	-10000	0	-0.97	98	98
CCR5	-0.19	0.46	-10000	0	-1.1	81	81
IL1B	-0.053	0.17	-10000	0	-0.42	81	81
STAT6	-0.066	0.18	-10000	0	-0.37	79	79
STAT4	-0.024	0.13	-10000	0	-0.42	50	50
STAT3	0.015	0.04	-10000	0	-0.52	3	3
STAT1	-0.02	0.12	-10000	0	-0.33	58	58
NFKB1	0.017	0.023	-10000	0	-0.52	1	1
NFKB2	0.015	0.031	-10000	0	-0.32	4	4
IL12B	0	0.077	-10000	0	-0.34	21	21
CD8A	-0.001	0.008	-10000	0	-10000	0	0
CD8B	0.001	0.07	-10000	0	-0.28	29	29
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.029	0.12	0.35	30	-10000	0	30
IL2RB	-0.016	0.12	-10000	0	-0.43	40	40
proteasomal ubiquitin-dependent protein catabolic process	-0.16	0.38	-10000	0	-0.8	113	113
IL2RG	-0.002	0.078	-10000	0	-0.28	35	35
IL12	-0.011	0.089	-10000	0	-0.36	14	14
STAT5A	0.011	0.056	-10000	0	-0.42	8	8
CD247	-0.11	0.21	-10000	0	-0.42	153	153
IL2	0.011	0.051	-10000	0	-0.33	10	10
SPHK2	0.017	0.023	-10000	0	-0.52	1	1
FRAP1	0.018	0	-10000	0	-10000	0	0
IL12A	-0.019	0.095	-10000	0	-0.28	55	55
IL12/IL12R/TYK2/JAK2	-0.25	0.54	-10000	0	-1.1	125	125
MAP2K3	-0.18	0.44	-10000	0	-0.99	97	97
RIPK2	0.013	0.04	-10000	0	-0.28	9	9
MAP2K6	-0.19	0.45	-10000	0	-0.97	106	106
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.002	0.08	-10000	0	-0.52	12	12
IL18RAP	-0.071	0.19	-10000	0	-0.4	114	114
IL12Rbeta1/TYK2	0.018	0.032	-10000	0	-10000	0	0
EOMES	-0.059	0.26	-10000	0	-1.3	21	21
STAT1 (dimer)	-0.2	0.39	-10000	0	-0.8	124	124
T cell proliferation	-0.12	0.31	-10000	0	-0.66	106	106
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.01	0.12	-10000	0	-0.41	37	37
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.2	0.3	-10000	0	-0.72	109	109
ATF2	-0.15	0.4	-10000	0	-0.89	94	94

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.062	0.17	-9999	-0.43	52	52
NF kappa B1 p50/RelA/I kappa B alpha	-0.043	0.18	-9999	-0.49	44	44
alphaV/beta3 Integrin/Osteopontin/Src	-0.098	0.18	-9999	-0.39	131	131
AP1	-0.15	0.26	-9999	-0.58	105	105
ILK	-0.064	0.16	-9999	-0.41	47	47
bone resorption	-0.055	0.17	-9999	-0.42	51	51
PTK2B	0.017	0.017	-9999	-0.25	2	2
PYK2/p130Cas	-0.059	0.17	-9999	-0.39	59	59
ITGAV	-0.001	0.1	-9999	-0.49	21	21
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.007	0.081	-9999	-0.37	21	21
alphaV/beta3 Integrin/Osteopontin	-0.076	0.18	-9999	-0.34	142	142
MAP3K1	-0.09	0.18	-9999	-0.32	166	166
JUN	-0.034	0.15	-9999	-0.46	57	57
MAPK3	-0.064	0.17	-9999	-0.46	49	49
MAPK1	-0.064	0.17	-9999	-0.46	50	50
Rac1/GDP	0.013	0	-9999	-10000	0	0
NFKB1	0.017	0.023	-9999	-0.52	1	1
MAPK8	-0.08	0.17	-9999	-0.41	67	67
ITGB3	0.003	0.077	-9999	-0.32	25	25
NFKBIA	-0.063	0.19	-9999	-0.5	51	51
FOS	-0.11	0.2	-9999	-0.37	171	171
CD44	-0.004	0.1	-9999	-0.43	26	26
CHUK	0.005	0.081	-9999	-0.5	13	13
PLAU	-0.14	0.38	-9999	-1.2	56	56
NF kappa B1 p50/RelA	-0.047	0.19	-9999	-0.52	45	45
BCAR1	0.017	0.012	-9999	-0.25	1	1
RELA	0.018	0	-9999	-10000	0	0
alphaV beta3 Integrin	0.003	0.1	-9999	-0.42	22	22
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.085	0.18	-9999	-0.32	162	162
VAV3	-0.12	0.2	-9999	-0.43	100	100
MAP3K14	-0.069	0.17	-9999	-0.31	137	137
ROCK2	0.013	0.048	-9999	-0.47	5	5
SPP1	-0.14	0.23	-9999	-0.42	188	188
RAC1	0.018	0	-9999	-10000	0	0
Rac1/GTP	-0.11	0.18	-9999	-0.41	92	92
MMP2	-0.13	0.24	-9999	-0.54	103	103

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0	0.058	-9999	-0.26	23	23
ARNO/beta Arrestin1-2	-0.013	0.089	-9999	-0.24	59	59
EGFR	-0.079	0.18	-9999	-0.35	139	139
EPHA2	0.008	0.059	-9999	-0.33	14	14
USP6	0.012	0.04	-9999	-0.25	12	12
IQSEC1	0.016	0.026	-9999	-0.39	2	2
EGFR/EGFR/EGF/EGF	-0.15	0.2	-9999	-0.42	173	173
ARRB2	0.011	0.052	-9999	-0.32	12	12
mol:GTP	0.006	0.015	-9999	-0.13	2	2
ARRB1	0.004	0.075	-9999	-0.37	18	18
FBXO8	0.015	0.04	-9999	-0.52	3	3
TSHR	0.008	0.071	-9999	-0.5	10	10
EGF	-0.14	0.23	-9999	-0.42	193	193
somatostatin receptor activity	0	0	-9999	-0.001	95	95
ARAP2	0	0	-9999	0	110	110
mol:GDP	-0.054	0.11	-9999	-0.25	89	89
mol:PI-3-4-5-P3	0	0	-9999	-0.001	96	96
ITGA2B	0.016	0.02	-9999	-0.25	3	3
ARF6	0.016	0.033	-9999	-0.52	2	2
Ephrin A1/EPHA2/NCK1/GIT1	0.025	0.071	-9999	-0.27	24	24
ADAP1	0	0	-9999	0	87	87
KIF13B	-0.002	0.095	-9999	-0.43	23	23
HGF/MET	0.007	0.073	-9999	-0.38	13	13
PXN	0.018	0	-9999	-10000	0	0
ARF6/GTP	-0.067	0.11	-9999	-0.27	93	93
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.12	0.18	-9999	-0.35	173	173
ADRB2	-0.045	0.16	-9999	-0.4	80	80
receptor agonist activity	0	0	-9999	0	92	92
actin filament binding	0	0	-9999	0	96	96
SRC	0.015	0.035	-9999	-0.43	3	3
ITGB3	0.002	0.075	-9999	-0.32	25	25
GNAQ	0	0	-9999	-0.001	88	88
EFA6/PI-4-5-P2	0	0	-9999	-0.001	90	90
ARF6/GDP	-0.003	0.059	-9999	-0.3	5	5
ARF6/GDP/GULP/ACAP1	-0.058	0.13	-9999	-0.32	85	85
alphaIIb/beta3 Integrin/paxillin/GIT1	0.034	0.048	-9999	-0.26	8	8
ACAP1	0	0	-9999	0	21	21
ACAP2	0	0	-9999	0	104	104
LHCGR/beta Arrestin2	0.009	0.07	-9999	-0.44	12	12
EFNA1	0	0.094	-9999	-0.49	18	18
HGF	0.008	0.069	-9999	-0.45	11	11
CYTH3	0	0	-9999	-0.001	95	95
CYTH2	-0.001	0.002	-9999	-0.004	100	100
NCK1	0.011	0.045	-9999	-0.28	12	12
fibronectin binding	0	0	-9999	0	75	75
endosomal lumen acidification	0	0	-9999	0	82	82
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.035	0.15	-9999	-0.44	61	61
GNAQ/ARNO	-0.001	0.003	-9999	-0.006	89	89
mol:Phosphatidic acid	0	0	-9999	0	104	104
PIP3-E	0.004	0.068	-9999	-0.3	23	23
MET	0	0.075	-9999	-0.29	31	31
GNA14	-0.08	0.18	-9999	-0.35	140	140
GNA15	0.002	0.076	-9999	-0.34	23	23
GIT1	0.014	0.035	-9999	-0.3	6	6
mol:PI-4-5-P2	0	0	-9999	-0.001	92	92
GNA11	0.013	0.047	-9999	-0.52	4	4
LHCGR	0.003	0.083	-9999	-0.46	16	16
AGTR1	-0.15	0.21	-9999	-0.36	231	231
desensitization of G-protein coupled receptor protein signaling pathway	0.009	0.07	-9999	-0.44	12	12
IPCEF1/ARNO	-0.095	0.14	-9999	-0.28	179	179
alphaIIb/beta3 Integrin	0.014	0.056	-9999	-0.36	7	7

×

IL23-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
CCL2	-0.23	0.53	-10000	0	-1.3	83	83
IL23A	-0.21	0.49	-10000	0	-1.2	73	73
NF kappa B1 p50/RelA/I kappa B alpha	-0.22	0.42	-10000	0	-1	87	87
positive regulation of T cell mediated cytotoxicity	-0.21	0.51	-10000	0	-1.1	90	90
ITGA3	-0.2	0.48	-10000	0	-1.1	82	82
IL17F	-0.097	0.32	-10000	0	-0.68	75	75
IL12B	0.004	0.084	-10000	0	-0.35	21	21
STAT1 (dimer)	-0.21	0.49	-10000	0	-1.1	91	91
CD4	-0.17	0.44	-10000	0	-1.1	58	58
IL23	-0.2	0.47	-10000	0	-1.1	73	73
IL23R	-0.011	0.18	-10000	0	-1.4	7	7
IL1B	-0.23	0.53	-10000	0	-1.3	82	82
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.18	0.44	-10000	0	-1.1	58	58
TYK2	0.013	0.024	-10000	0	-10000	0	0
STAT4	-0.024	0.13	-10000	0	-0.42	50	50
STAT3	0.015	0.041	-10000	0	-0.52	3	3
IL18RAP	-0.075	0.18	-10000	0	-0.41	114	114
IL12RB1	0.013	0.024	-10000	0	-10000	0	0
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
IL12Rbeta1/TYK2	0.017	0.031	-10000	0	-10000	0	0
IL23R/JAK2	-0.013	0.19	-10000	0	-1.3	7	7
positive regulation of chronic inflammatory response	-0.21	0.51	-10000	0	-1.1	90	90
natural killer cell activation	0.001	0.012	0.073	8	-10000	0	8
JAK2	0.011	0.065	-10000	0	-0.34	12	12
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
NFKB1	0.016	0.024	-10000	0	-0.52	1	1
RELA	0.017	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.19	0.45	-10000	0	-1.1	73	73
ALOX12B	-0.17	0.44	-10000	0	-1	70	70
CXCL1	-0.27	0.54	-10000	0	-1.2	112	112
T cell proliferation	-0.21	0.51	-10000	0	-1.1	90	90
NFKBIA	0.014	0.043	-10000	0	-0.46	4	4
IL17A	-0.052	0.26	-10000	0	-0.54	61	61
PI3K	-0.19	0.47	-10000	0	-1.1	88	88
IFNG	-0.027	0.05	0.12	2	-0.13	53	55
STAT3 (dimer)	-0.21	0.41	-10000	0	-0.99	89	89
IL18R1	-0.014	0.11	-10000	0	-0.41	37	37
IL23/IL23R/JAK2/TYK2/SOCS3	-0.08	0.28	-10000	0	-0.64	47	47
IL18/IL18R	-0.082	0.2	-10000	0	-0.41	117	117
macrophage activation	-0.015	0.017	-10000	0	-0.044	70	70
TNF	-0.2	0.49	-10000	0	-1.2	75	75
STAT3/STAT4	-0.24	0.45	-10000	0	-1.1	95	95
STAT4 (dimer)	-0.21	0.5	-10000	0	-1.1	95	95
IL18	-0.05	0.17	-10000	0	-0.44	76	76
IL19	-0.19	0.44	-10000	0	-1.1	70	70
STAT5A (dimer)	-0.2	0.49	-10000	0	-1.1	89	89
STAT1	-0.02	0.12	-10000	0	-0.33	58	58
SOCS3	0.005	0.074	-10000	0	-0.38	17	17
CXCL9	-0.27	0.57	-10000	0	-1.2	112	112
MPO	-0.17	0.44	-10000	0	-1.1	69	69
positive regulation of humoral immune response	-0.21	0.51	-10000	0	-1.1	90	90
IL23/IL23R/JAK2/TYK2	-0.22	0.54	-10000	0	-1.2	87	87
IL6	-0.26	0.55	-10000	0	-1.2	100	100
STAT5A	0.011	0.056	-10000	0	-0.42	8	8
IL2	0.008	0.053	-10000	0	-0.34	10	10
positive regulation of tyrosine phosphorylation of STAT protein	0.001	0.012	0.073	8	-10000	0	8
CD3E	-0.17	0.44	-10000	0	-1	69	69
keratinocyte proliferation	-0.21	0.51	-10000	0	-1.1	90	90
NOS2	-0.18	0.44	-10000	0	-0.96	91	91

×

Thromboxane A2 receptor 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
TGM2	-0.015	0.12	-10000	0	-0.38	44	44
GNB1/GNG2	-0.058	0.078	-10000	0	-0.18	138	138
AKT1	-0.023	0.12	-10000	0	-0.21	80	80
EGF	-0.14	0.23	-10000	0	-0.42	193	193
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.03	0.061	-10000	0	-0.29	5	5
mol:Ca2+	-0.048	0.17	-10000	0	-0.29	141	141
LYN	0.029	0.062	-10000	0	-0.29	5	5
RhoA/GTP	-0.041	0.056	-10000	0	-0.13	82	82
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.066	0.19	-10000	0	-0.35	142	142
GNG2	0.016	0.029	-10000	0	-0.34	3	3
ARRB2	0.018	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.004	0.1	-10000	0	-0.39	22	22
G beta5/gamma2	-0.075	0.1	-10000	0	-0.24	138	138
PRKCH	-0.062	0.19	-10000	0	-0.35	138	138
DNM1	0.013	0.047	-10000	0	-0.37	7	7
TXA2/TP beta/beta Arrestin3	0.006	0.019	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	-0.002	0.088	-10000	0	-0.35	29	29
G12 family/GTP	-0.096	0.13	-10000	0	-0.3	141	141
ADRBK1	0.018	0	-10000	0	-10000	0	0
ADRBK2	0.002	0.088	-10000	0	-0.49	16	16
RhoA/GTP/ROCK1	0.016	0.05	-10000	0	-0.31	12	12
mol:GDP	0.019	0.12	0.32	24	-10000	0	24
mol:NADP	0.017	0.012	-10000	0	-0.25	1	1
RAB11A	0.016	0.029	-10000	0	-0.34	3	3
PRKG1	0.017	0.012	-10000	0	-0.25	1	1
mol:IP3	-0.067	0.2	-10000	0	-0.37	141	141
cell morphogenesis	0.016	0.05	-10000	0	-0.31	12	12
PLCB2	-0.1	0.26	-10000	0	-0.5	139	139
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.016	0.073	-10000	0	-0.31	6	6
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.02	0.085	-10000	0	-0.35	15	15
RHOA	0.005	0.08	-10000	0	-0.52	12	12
PTGIR	0.016	0.033	-10000	0	-0.52	2	2
PRKCB1	-0.081	0.22	-10000	0	-0.4	142	142
GNAQ	0	0	-10000	0	-10000	0	0
mol:L-citrulline	0.017	0.012	-10000	0	-0.25	1	1
TXA2/TXA2-R family	-0.11	0.27	-10000	0	-0.52	140	140
LCK	-0.008	0.11	-10000	0	-0.37	16	16
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.034	0.044	-10000	0	-0.36	2	2
TXA2-R family/G12 family/GDP/G beta/gamma	0.029	0.059	-10000	0	-0.53	5	5
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.034	0.044	-10000	0	-0.36	2	2
MAPK14	-0.033	0.13	-10000	0	-0.23	137	137
TGM2/GTP	-0.079	0.23	-10000	0	-0.41	147	147
MAPK11	-0.033	0.13	-10000	0	-0.23	137	137
ARHGEF1	-0.021	0.1	-10000	0	-0.17	136	136
GNAI2	0.006	0.075	-10000	0	-0.48	12	12
JNK cascade	-0.069	0.21	-10000	0	-0.38	140	140
RAB11/GDP	0.016	0.028	-10000	0	-0.34	3	3
ICAM1	-0.052	0.17	-10000	0	-0.3	139	139
cAMP biosynthetic process	-0.063	0.19	-10000	0	-0.34	139	139
Gq family/GTP/EBP50	-0.038	0.11	-10000	0	-0.29	63	63
actin cytoskeleton reorganization	0.016	0.05	-10000	0	-0.31	12	12
SRC	0.029	0.062	-10000	0	-0.29	5	5
GNB5	0.005	0.081	-10000	0	-0.5	13	13
GNB1	0.013	0.052	-10000	0	-0.52	5	5
EGF/EGFR	-0.028	0.11	-10000	0	-0.28	49	49
VCAM1	-0.054	0.17	-10000	0	-0.31	145	145
TP beta/Gq family/GDP/G beta5/gamma2	-0.004	0.1	-10000	0	-0.39	22	22
platelet activation	-0.042	0.17	-10000	0	-0.3	139	139
PGI2/IP	0.012	0.024	-10000	0	-0.38	2	2
PRKACA	0.015	0.046	-10000	0	-0.26	12	12
Gq family/GDP/G beta5/gamma2	-0.005	0.096	-10000	0	-0.36	22	22
TXA2/TP beta/beta Arrestin2	-0.005	0.044	-10000	0	-0.56	3	3
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.021	0.044	-10000	0	-0.24	12	12
mol:DAG	-0.079	0.22	-10000	0	-0.41	140	140
EGFR	-0.079	0.18	-10000	0	-0.35	139	139
TXA2/TP alpha	-0.09	0.25	-10000	0	-0.46	139	139
Gq family/GTP	-0.038	0.078	-10000	0	-0.24	58	58
YES1	0.026	0.07	-10000	0	-0.32	7	7
GNAI2/GTP	-0.015	0.055	-10000	0	-0.27	11	11
PGD2/DP	-0.001	0.062	-10000	0	-0.24	29	29
SLC9A3R1	-0.043	0.16	-10000	0	-0.44	70	70
FYN	0.026	0.073	-10000	0	-0.31	12	12
mol:NO	0.017	0.012	-10000	0	-0.25	1	1
GNA15	0.002	0.076	-10000	0	-0.34	23	23
PGK/cGMP	0.023	0.01	-10000	0	-0.13	1	1
RhoA/GDP	0.006	0.079	-10000	0	-0.51	12	12
TP alpha/TGM2/GDP/G beta/gamma	0.028	0.078	-10000	0	-0.37	7	7
NOS3	0.017	0.012	-10000	0	-0.26	1	1
RAC1	0.018	0	-10000	0	-10000	0	0
PRKCA	-0.061	0.19	-10000	0	-0.34	139	139
PRKCB	-0.064	0.19	-10000	0	-0.35	141	141
PRKCE	-0.062	0.19	-10000	0	-0.35	139	139
PRKCD	-0.068	0.2	-10000	0	-0.37	139	139
PRKCG	-0.069	0.2	-10000	0	-0.37	140	140
muscle contraction	-0.095	0.25	-10000	0	-0.48	140	140
PRKCZ	-0.06	0.18	-10000	0	-0.34	140	140
ARR3	0.017	0.012	-10000	0	-0.25	1	1
TXA2/TP beta	0.028	0.059	-10000	0	-0.23	18	18
PRKCQ	-0.068	0.2	-10000	0	-0.35	145	145
MAPKKK cascade	-0.086	0.23	-10000	0	-0.44	140	140
SELE	-0.077	0.2	-10000	0	-0.38	144	144
TP beta/GNAI2/GDP/G beta/gamma	0.038	0.068	-10000	0	-0.37	7	7
ROCK1	0.018	0	-10000	0	-10000	0	0
GNA14	-0.079	0.18	-10000	0	-0.35	140	140
chemotaxis	-0.13	0.31	-10000	0	-0.6	140	140
GNA12	0.018	0	-10000	0	-10000	0	0
GNA13	0.011	0.055	-10000	0	-0.36	10	10
GNA11	0.014	0.047	-10000	0	-0.52	4	4
Rac1/GTP	0.013	0.002	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.027	0.13	-10000	0	-0.26	110	110
epithelial cell differentiation	-0.007	0.1	-10000	0	-0.26	76	76
CYFIP2	-0.042	0.16	-10000	0	-0.47	65	65
ENAH	0.012	0.096	-10000	0	-0.31	14	14
EGFR	-0.079	0.18	-10000	0	-0.35	139	139
EPHA2	0.008	0.059	-10000	0	-0.33	14	14
MYO6	-0.012	0.11	-10000	0	-0.25	90	90
CTNNB1	0.001	0.09	-10000	0	-0.45	19	19
ABI1/Sra1/Nap1	-0.004	0.11	-10000	0	-0.31	53	53
AQP5	-0.086	0.19	-10000	0	-0.46	87	87
CTNND1	0.016	0.029	-10000	0	-0.34	3	3
mol:PI-4-5-P2	-0.004	0.1	-10000	0	-0.24	78	78
regulation of calcium-dependent cell-cell adhesion	-0.014	0.1	-10000	0	-0.24	82	82
EGF	-0.14	0.23	-10000	0	-0.42	193	193
NCKAP1	0.015	0.031	-10000	0	-0.32	4	4
AQP3	-0.088	0.2	-10000	0	-0.49	86	86
cortical microtubule organization	-0.007	0.1	-10000	0	-0.26	76	76
GO:0000145	-0.006	0.095	-10000	0	-0.23	78	78
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.004	0.11	-10000	0	-0.26	76	76
MLLT4	-0.006	0.11	-10000	0	-0.46	26	26
ARF6/GDP	-0.04	0.086	-10000	0	-0.39	12	12
ARF6	0.016	0.033	-10000	0	-0.52	2	2
Ephrin A1/EPHA2/NCK1/GIT1	0.025	0.071	-10000	0	-0.27	24	24
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.006	0.12	-10000	0	-0.44	15	15
PVRL2	0.002	0.089	-10000	0	-0.52	15	15
ZYX	-0.009	0.11	-10000	0	-0.24	84	84
ARF6/GTP	0.03	0.072	-10000	0	-0.27	22	22
CDH1	-0.049	0.17	-10000	0	-0.48	70	70
EGFR/EGFR/EGF/EGF	-0.14	0.14	-10000	0	-0.38	92	92
RhoA/GDP	-0.01	0.11	-10000	0	-0.25	85	85
actin cytoskeleton organization	-0.007	0.11	-10000	0	-0.24	76	76
IGF-1R heterotetramer	-0.083	0.2	-10000	0	-0.47	110	110
GIT1	0.014	0.035	-10000	0	-0.3	6	6
IGF1R	-0.083	0.2	-10000	0	-0.47	110	110
IGF1	-0.1	0.2	-10000	0	-0.41	146	146
DIAPH1	-0.055	0.18	-10000	0	-0.58	53	53
Wnt receptor signaling pathway	0.007	0.1	0.26	76	-10000	0	76
RHOA	0.005	0.08	-10000	0	-0.52	12	12
RhoA/GTP	-0.044	0.089	-10000	0	-0.37	16	16
CTNNA1	0.017	0.023	-10000	0	-0.52	1	1
VCL	-0.007	0.11	-10000	0	-0.24	76	76
EFNA1	0	0.094	-10000	0	-0.49	18	18
LPP	-0.003	0.1	-10000	0	-0.29	17	17
Ephrin A1/EPHA2	-0.044	0.094	-10000	0	-0.24	91	91
SEC6/SEC8	-0.045	0.092	-10000	0	-0.41	10	10
MGAT3	-0.014	0.11	-10000	0	-0.25	82	82
HGF/MET	-0.044	0.089	-10000	0	-0.28	20	20
HGF	0.008	0.069	-10000	0	-0.45	11	11
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.027	0.13	-10000	0	-0.26	110	110
actin cable formation	0.017	0.1	-10000	0	-0.28	21	21
KIAA1543	0.001	0.1	-10000	0	-0.38	9	9
KIFC3	-0.005	0.1	-10000	0	-0.24	77	77
NCK1	0.011	0.045	-10000	0	-0.28	12	12
EXOC3	0.017	0.012	-10000	0	-0.25	1	1
ACTN1	-0.009	0.11	-10000	0	-0.24	85	85
NCK1/GIT1	0.019	0.042	-10000	0	-0.44	2	2
mol:GDP	-0.007	0.1	-10000	0	-0.26	76	76
EXOC4	0.016	0.033	-10000	0	-0.52	2	2
STX4	-0.003	0.1	-10000	0	-0.24	76	76
PIP5K1C	-0.004	0.1	-10000	0	-0.24	78	78
LIMA1	-0.024	0.14	-10000	0	-0.52	41	41
ABI1	0.016	0.02	-10000	0	-0.25	3	3
ROCK1	0.009	0.1	-10000	0	-0.32	16	16
adherens junction assembly	0.012	0.11	-10000	0	-0.52	5	5
IGF-1R heterotetramer/IGF1	-0.12	0.16	-10000	0	-0.3	203	203
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.002	0.1	-10000	0	-0.39	33	33
MET	0	0.075	-10000	0	-0.29	31	31
PLEKHA7	-0.003	0.099	-10000	0	-0.24	77	77
mol:GTP	0.024	0.07	-10000	0	-0.27	24	24
establishment of epithelial cell apical/basal polarity	0.006	0.11	-10000	0	-0.41	10	10
cortical actin cytoskeleton stabilization	-0.027	0.13	-10000	0	-0.26	110	110
regulation of cell-cell adhesion	-0.007	0.11	-10000	0	-0.24	76	76
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.027	0.13	-10000	0	-0.26	110	110

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.1	0.26	-10000	0	-0.62	82	82
IHH	-0.014	0.093	-10000	0	-0.48	14	14
SHH Np/Cholesterol/GAS1	-0.057	0.14	-10000	0	-0.29	133	133
LRPAP1	0.016	0.026	-10000	0	-0.39	2	2
dorsoventral neural tube patterning	0.056	0.14	0.29	133	-10000	0	133
SMO/beta Arrestin2	-0.055	0.17	-10000	0	-0.48	45	45
SMO	-0.066	0.18	-10000	0	-0.5	49	49
AKT1	-0.027	0.13	-10000	0	-0.5	22	22
ARRB2	0.018	0	-10000	0	-10000	0	0
BOC	-0.02	0.12	-10000	0	-0.38	50	50
ADRBK1	0.018	0	-10000	0	-10000	0	0
heart looping	-0.065	0.18	-10000	0	-0.49	49	49
STIL	-0.052	0.15	-10000	0	-0.37	53	53
DHH N/PTCH2	0.026	0	-10000	0	-10000	0	0
DHH N/PTCH1	-0.028	0.13	-10000	0	-0.37	24	24
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
DHH	0.018	0	-10000	0	-10000	0	0
PTHLH	-0.12	0.31	-10000	0	-0.83	66	66
determination of left/right symmetry	-0.065	0.18	-10000	0	-0.49	49	49
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
skeletal system development	-0.12	0.31	-10000	0	-0.82	66	66
IHH N/Hhip	0.004	0.068	-10000	0	-0.29	22	22
DHH N/Hhip	0.021	0.037	-10000	0	-0.37	3	3
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.065	0.18	-10000	0	-0.49	49	49
pancreas development	0.011	0.052	-10000	0	-0.33	11	11
HHAT	-0.045	0.17	-10000	0	-0.51	63	63
PI3K	0.005	0.082	-10000	0	-0.37	21	21
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.072	0.19	-10000	0	-0.47	98	98
somite specification	-0.065	0.18	-10000	0	-0.49	49	49
SHH Np/Cholesterol/PTCH1	-0.049	0.14	-10000	0	-0.36	49	49
SHH Np/Cholesterol/PTCH2	-0.007	0.098	-10000	0	-0.28	61	61
SHH Np/Cholesterol/Megalin	-0.1	0.18	-10000	0	-0.33	181	181
SHH	-0.021	0.13	-10000	0	-0.37	61	61
catabolic process	-0.042	0.14	-10000	0	-0.33	76	76
SMO/Vitamin D3	-0.061	0.17	-10000	0	-0.4	63	63
SHH Np/Cholesterol/Hhip	-0.01	0.1	-10000	0	-0.28	64	64
LRP2	-0.16	0.24	-10000	0	-0.48	183	183
receptor-mediated endocytosis	-0.12	0.2	-10000	0	-0.46	90	90
SHH Np/Cholesterol/BOC	-0.027	0.12	-10000	0	-0.28	85	85
SHH Np/Cholesterol/CDO	-0.019	0.11	-10000	0	-0.29	74	74
mesenchymal cell differentiation	0.011	0.1	0.28	64	-10000	0	64
mol:Vitamin D3	-0.047	0.14	-10000	0	-0.36	49	49
IHH N/PTCH2	0.01	0.055	-10000	0	-0.32	11	11
CDON	-0.004	0.099	-10000	0	-0.41	27	27
IHH N/PTCH1	-0.04	0.14	-10000	0	-0.33	76	76
Megalin/LRPAP1	-0.1	0.18	-10000	0	-0.37	158	158
PTCH2	0.018	0	-10000	0	-10000	0	0
SHH Np/Cholesterol	-0.017	0.097	-10000	0	-0.28	61	61
PTCH1	-0.043	0.14	-10000	0	-0.33	76	76
HHIP	0.011	0.052	-10000	0	-0.33	11	11

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.011	0.02	-10000	0	-0.24	3	3
GNB1/GNG2	-0.031	0.13	-10000	0	-0.28	107	107
regulation of S phase of mitotic cell cycle	-0.031	0.12	-10000	0	-0.24	120	120
GNAO1	0.016	0.024	-10000	0	-0.25	4	4
HRAS	0.011	0.051	-10000	0	-0.41	7	7
SHBG/T-DHT	0.012	0	-10000	0	-10000	0	0
PELP1	0.017	0.001	-10000	0	-10000	0	0
AKT1	0.008	0.038	-10000	0	-0.26	9	9
MAP2K1	-0.032	0.12	-10000	0	-0.32	32	32
T-DHT/AR	-0.064	0.16	-10000	0	-0.38	104	104
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.005	164	164
GNAI2	0.006	0.075	-10000	0	-0.48	12	12
GNAI3	0.018	0	-10000	0	-10000	0	0
GNAI1	-0.017	0.12	-10000	0	-0.38	46	46
mol:GDP	-0.089	0.17	-10000	0	-0.43	103	103
cell proliferation	-0.066	0.18	-10000	0	-0.4	83	83
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
FOS	-0.13	0.3	-10000	0	-0.81	76	76
mol:Ca2+	-0.014	0.022	-10000	0	-0.08	23	23
MAPK3	-0.05	0.14	-10000	0	-0.42	32	32
MAPK1	-0.029	0.092	-10000	0	-0.27	26	26
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
mol:IP3	-0.001	0.002	-10000	0	-0.003	166	166
cAMP biosynthetic process	0.013	0.021	-10000	0	-10000	0	0
GNG2	0.016	0.029	-10000	0	-0.34	3	3
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.003	166	166
HRAS/GTP	-0.036	0.12	-10000	0	-0.26	107	107
actin cytoskeleton reorganization	-0.01	0.049	-10000	0	-0.24	21	21
SRC	0.015	0.035	-10000	0	-0.43	3	3
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.003	166	166
PI3K	0.006	0.07	-10000	0	-0.31	21	21
apoptosis	0.064	0.17	0.41	82	-10000	0	82
T-DHT/AR/PELP1	-0.044	0.13	-10000	0	-0.32	103	103
HRAS/GDP	-0.063	0.18	-10000	0	-0.4	105	105
CREB1	-0.069	0.18	-10000	0	-0.44	82	82
RAC1-CDC42/GTP	0.02	0.057	-10000	0	-0.24	21	21
AR	-0.089	0.21	-10000	0	-0.52	104	104
GNB1	0.013	0.052	-10000	0	-0.52	5	5
RAF1	-0.033	0.12	-10000	0	-0.25	107	107
RAC1-CDC42/GDP	-0.047	0.17	-10000	0	-0.38	103	103
T-DHT/AR/PELP1/Src	-0.032	0.12	-10000	0	-0.28	105	105
MAP2K2	-0.033	0.12	-10000	0	-0.33	32	32
T-DHT/AR/PELP1/Src/PI3K	-0.032	0.12	-10000	0	-0.24	120	120
GNAZ	0.001	0.088	-10000	0	-0.44	19	19
SHBG	0.018	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.002	0.1	-10000	0	-0.44	15	15
mol:T-DHT	0	0.001	-10000	0	-0.003	52	52
RAC1	0.018	0	-10000	0	-10000	0	0
GNRH1	0	0.057	-10000	0	-0.23	26	26
Gi family/GTP	-0.022	0.092	-10000	0	-0.28	21	21
CDC42	0.018	0	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.049	0.17	-9999	-0.44	77	77
PLK4	0.008	0.065	-9999	-0.38	13	13
regulation of centriole replication	-0.029	0.13	-9999	-0.37	59	59

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.02	0.13	-9999	-0.32	78	78
E-cadherin/beta catenin	-0.034	0.14	-9999	-0.38	74	74
CTNNB1	0.001	0.09	-9999	-0.45	19	19
JUP	0.011	0.056	-9999	-0.42	8	8
CDH1	-0.049	0.17	-9999	-0.48	70	70

×

BMP receptor 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.065	0.13	-9999	-0.28	97	97
SMAD6-7/SMURF1	0.034	0.021	-9999	-0.3	1	1
NOG	0.009	0.056	-9999	-0.31	14	14
SMAD9	-0.023	0.12	-9999	-0.65	12	12
SMAD4	0.009	0.067	-9999	-0.49	9	9
SMAD5	-0.062	0.14	-9999	-0.37	60	60
BMP7/USAG1	-0.18	0.18	-9999	-0.39	202	202
SMAD5/SKI	-0.051	0.14	-9999	-0.37	48	48
SMAD1	0.024	0.061	-9999	-0.34	9	9
BMP2	-0.019	0.11	-9999	-0.32	58	58
SMAD1/SMAD1/SMAD4	-0.01	0.044	-9999	-0.33	3	3
BMPR1A	0.009	0.068	-9999	-0.47	10	10
BMPR1B	-0.11	0.16	-9999	-0.29	216	216
BMPR1A-1B/BAMBI	-0.13	0.17	-9999	-0.36	157	157
AHSG	0.016	0.024	-9999	-0.25	4	4
CER1	0.017	0.012	-9999	-0.25	1	1
BMP2-4/CER1	-0.052	0.14	-9999	-0.35	84	84
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.053	0.14	-9999	-0.35	56	56
BMP2-4 (homodimer)	-0.075	0.16	-9999	-0.42	83	83
RGMB	0.009	0.07	-9999	-0.52	9	9
BMP6/BMPR2/BMPR1A-1B	-0.042	0.11	-9999	-0.3	53	53
RGMA	-0.027	0.12	-9999	-0.3	75	75
SMURF1	0.018	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.072	0.14	-9999	-0.32	96	96
BMP2-4/USAG1	-0.2	0.2	-9999	-0.38	245	245
SMAD6/SMURF1/SMAD5	-0.051	0.14	-9999	-0.38	47	47
SOSTDC1	-0.23	0.23	-9999	-0.39	314	314
BMP7/BMPR2/BMPR1A-1B	-0.06	0.12	-9999	-0.3	68	68
SKI	0.017	0.017	-9999	-0.25	2	2
BMP6 (homodimer)	-0.006	0.089	-9999	-0.3	40	40
HFE2	0.004	0.08	-9999	-0.45	15	15
ZFYVE16	0.016	0.033	-9999	-0.52	2	2
MAP3K7	0.016	0.02	-9999	-0.25	3	3
BMP2-4/CHRD	-0.059	0.16	-9999	-0.37	84	84
SMAD5/SMAD5/SMAD4	-0.055	0.14	-9999	-0.36	58	58
MAPK1	0.016	0.033	-9999	-0.52	2	2
TAK1/TAB family	-0.032	0.13	-9999	-0.42	26	26
BMP7 (homodimer)	-0.041	0.13	-9999	-0.29	101	101
NUP214	0.016	0.026	-9999	-0.39	2	2
BMP6/FETUA	0.008	0.065	-9999	-0.36	8	8
SMAD1/SKI	0.032	0.06	-9999	-0.34	7	7
SMAD6	0.016	0.024	-9999	-0.25	4	4
CTDSP2	0.014	0.044	-9999	-0.41	5	5
BMP2-4/FETUA	-0.053	0.14	-9999	-0.35	84	84
MAP3K7IP1	0.018	0	-9999	-10000	0	0
GREM1	-0.038	0.16	-9999	-0.45	63	63
BMPR2 (homodimer)	0.016	0.033	-9999	-0.52	2	2
GADD34/PP1CA	0.03	0.04	-9999	-0.3	5	5
BMPR1A-1B (homodimer)	-0.068	0.12	-9999	-0.38	39	39
CHRDL1	-0.013	0.09	-9999	-0.27	56	56
ENDOFIN/SMAD1	0.032	0.063	-9999	-0.35	9	9
SMAD6-7/SMURF1/SMAD1	0.046	0.058	-9999	-0.31	7	7
SMAD6/SMURF1	0.018	0	-9999	-10000	0	0
BAMBI	-0.13	0.22	-9999	-0.41	182	182
SMURF2	0.009	0.058	-9999	-0.34	13	13
BMP2-4/CHRDL1	-0.068	0.16	-9999	-0.36	97	97
BMP2-4/GREM1	-0.085	0.18	-9999	-0.37	119	119
SMAD7	0.016	0.026	-9999	-0.39	2	2
SMAD8A/SMAD8A/SMAD4	-0.016	0.11	-9999	-0.53	16	16
SMAD1/SMAD6	0.033	0.06	-9999	-0.34	7	7
TAK1/SMAD6	0.025	0.014	-9999	-10000	0	0
BMP7	-0.041	0.13	-9999	-0.29	101	101
BMP6	-0.006	0.089	-9999	-0.3	40	40
MAP3K7IP2	0.014	0.047	-9999	-0.52	4	4
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.052	0.13	-9999	-0.31	67	67
PPM1A	0.016	0.026	-9999	-0.39	2	2
SMAD1/SMURF2	0.029	0.067	-9999	-0.34	9	9
SMAD7/SMURF1	0.025	0.019	-9999	-0.37	1	1
CTDSPL	0.011	0.062	-9999	-0.52	7	7
PPP1CA	0.011	0.048	-9999	-0.3	11	11
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0.016	0.033	-9999	-0.52	2	2
PPP1R15A	0.016	0.029	-9999	-0.34	3	3
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.081	0.16	-9999	-0.34	106	106
CHRD	0.003	0.073	-9999	-0.33	22	22
BMPR2	0.016	0.033	-9999	-0.52	2	2
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.074	0.15	-9999	-0.33	96	96
BMP4	-0.092	0.19	-9999	-0.39	143	143
FST	-0.017	0.11	-9999	-0.32	54	54
BMP2-4/NOG	-0.056	0.15	-9999	-0.35	88	88
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.048	0.11	-9999	-0.3	53	53

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.042	0.19	-9999	-0.51	66	66
Syndecan-4/Syndesmos	-0.044	0.21	-9999	-0.51	71	71
positive regulation of JNK cascade	-0.072	0.22	-9999	-0.51	88	88
Syndecan-4/ADAM12	-0.071	0.24	-9999	-0.54	94	94
CCL5	-0.051	0.18	-9999	-0.49	71	71
Rac1/GDP	0.013	0	-9999	-10000	0	0
DNM2	0.017	0.012	-9999	-0.25	1	1
ITGA5	0.015	0.035	-9999	-0.43	3	3
SDCBP	0.003	0.081	-9999	-0.4	19	19
PLG	0.016	0.033	-9999	-0.51	2	2
ADAM12	-0.051	0.17	-9999	-0.47	74	74
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.01	0.063	-9999	-0.49	8	8
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.006	0.012	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.041	0.21	-9999	-0.51	71	71
Syndecan-4/CXCL12/CXCR4	-0.077	0.24	-9999	-0.54	88	88
Syndecan-4/Laminin alpha3	-0.08	0.23	-9999	-0.55	77	77
MDK	-0.016	0.12	-9999	-0.37	46	46
Syndecan-4/FZD7	-0.07	0.23	-9999	-0.53	85	85
Syndecan-4/Midkine	-0.055	0.21	-9999	-0.52	76	76
FZD7	-0.049	0.16	-9999	-0.4	85	85
Syndecan-4/FGFR1/FGF	-0.074	0.22	-9999	-0.49	87	87
THBS1	-0.025	0.14	-9999	-0.52	42	42
integrin-mediated signaling pathway	-0.062	0.22	-9999	-0.51	84	84
positive regulation of MAPKKK cascade	-0.072	0.22	-9999	-0.51	88	88
Syndecan-4/TACI	-0.042	0.2	-9999	-0.51	72	72
CXCR4	-0.028	0.14	-9999	-0.42	55	55
cell adhesion	-0.008	0.1	-9999	-0.29	56	56
Syndecan-4/Dynamin	-0.04	0.2	-9999	-0.51	71	71
Syndecan-4/TSP1	-0.06	0.22	-9999	-0.52	81	81
Syndecan-4/GIPC	-0.042	0.2	-9999	-0.51	71	71
Syndecan-4/RANTES	-0.072	0.23	-9999	-0.55	78	78
ITGB1	0.014	0.044	-9999	-0.41	5	5
LAMA1	0.015	0.026	-9999	-0.25	5	5
LAMA3	-0.07	0.19	-9999	-0.43	103	103
RAC1	0.018	0	-9999	-10000	0	0
PRKCA	0.018	0.05	-9999	-0.24	6	6
Syndecan-4/alpha-Actinin	-0.045	0.21	-9999	-0.52	73	73
TFPI	0.004	0.061	-9999	-0.26	25	25
F2	0.017	0.007	-9999	-10000	0	0
alpha5/beta1 Integrin	0.022	0.041	-9999	-0.37	5	5
positive regulation of cell adhesion	-0.072	0.22	-9999	-0.52	77	77
ACTN1	0.005	0.079	-9999	-0.48	13	13
TNC	-0.039	0.14	-9999	-0.36	79	79
Syndecan-4/CXCL12	-0.067	0.23	-9999	-0.54	82	82
FGF6	0.009	0.066	-9999	-0.52	8	8
RHOA	0.005	0.08	-9999	-0.52	12	12
CXCL12	-0.041	0.16	-9999	-0.47	64	64
TNFRSF13B	0.013	0.035	-9999	-0.25	9	9
FGF2	-0.064	0.16	-9999	-0.34	122	122
FGFR1	-0.013	0.11	-9999	-0.35	44	44
Syndecan-4/PI-4-5-P2	-0.05	0.2	-9999	-0.52	71	71
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.047	0.16	-9999	-0.45	73	73
cell migration	0.002	0.008	-9999	-10000	0	0
PRKCD	0.015	0.041	-9999	-0.44	4	4
vasculogenesis	-0.057	0.21	-9999	-0.5	81	81
SDC4	-0.053	0.22	-9999	-0.55	71	71
Syndecan-4/Tenascin C	-0.065	0.22	-9999	-0.53	84	84
Syndecan-4/PI-4-5-P2/PKC alpha	-0.005	0.009	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.047	0.21	-9999	-0.52	73	73
MMP9	-0.04	0.17	-9999	-0.5	60	60
Rac1/GTP	-0.008	0.1	-9999	-0.3	56	56
cytoskeleton organization	-0.041	0.2	-9999	-0.49	71	71
GIPC1	0.014	0.042	-9999	-0.45	4	4
Syndecan-4/TFPI	-0.046	0.21	-9999	-0.51	73	73

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.1	0.3	-10000	0	-0.9	54	54
epithelial cell differentiation	-0.1	0.23	-10000	0	-0.7	59	59
ITCH	0.019	0.028	-10000	0	-10000	0	0
WWP1	-0.13	0.4	-10000	0	-1.4	44	44
FYN	0.008	0.067	-10000	0	-0.41	12	12
EGFR	-0.079	0.18	-10000	0	-0.35	139	139
PRL	0.015	0.031	-10000	0	-0.32	4	4
neuron projection morphogenesis	-0.032	0.22	-10000	0	-0.71	45	45
PTPRZ1	-0.028	0.11	-10000	0	-0.29	79	79
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.047	0.25	-10000	0	-0.82	45	45
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.08	0.27	-10000	0	-0.93	45	45
ADAM17	0.017	0.037	-10000	0	-0.28	3	3
ErbB4/ErbB4	-0.11	0.32	-10000	0	-0.99	52	52
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.1	0.3	-10000	0	-0.87	57	57
NCOR1	0.016	0.033	-10000	0	-0.52	2	2
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.073	0.26	-10000	0	-0.87	47	47
GRIN2B	-0.074	0.25	-10000	0	-0.8	49	49
ErbB4/ErbB2/betacellulin	-0.12	0.28	-10000	0	-0.72	73	73
STAT1	-0.02	0.12	-10000	0	-0.33	58	58
HBEGF	0.005	0.072	-10000	0	-0.36	18	18
PRLR	-0.03	0.15	-10000	0	-0.49	50	50
E4ICDs/ETO2	-0.17	0.34	-10000	0	-0.79	89	89
axon guidance	-0.079	0.28	-10000	0	-0.88	50	50
NEDD4	0.003	0.095	-10000	0	-0.53	15	15
Prolactin receptor/Prolactin receptor/Prolactin	-0.01	0.11	-10000	0	-0.37	45	45
CBFA2T3	-0.13	0.23	-10000	0	-0.45	162	162
ErbB4/ErbB2/HBEGF	-0.091	0.27	-10000	0	-0.81	54	54
MAPK3	-0.04	0.23	-10000	0	-0.75	45	45
STAT1 (dimer)	-0.11	0.3	-10000	0	-0.9	56	56
MAPK1	-0.04	0.23	-10000	0	-0.75	45	45
JAK2	0.01	0.053	-10000	0	-0.32	12	12
ErbB4/ErbB2/neuregulin 1 beta	-0.09	0.27	-10000	0	-0.82	53	53
NRG1	0.018	0.047	-10000	0	-0.28	6	6
NRG3	0	0.081	-10000	0	-0.34	26	26
NRG2	-0.017	0.1	-10000	0	-0.3	57	57
NRG4	0.009	0.051	-10000	0	-0.27	16	16
heart development	-0.079	0.28	-10000	0	-0.88	50	50
neural crest cell migration	-0.088	0.26	-10000	0	-0.8	53	53
ERBB2	-0.007	0.088	-10000	0	-0.35	18	18
WWOX/E4ICDs	-0.1	0.29	-10000	0	-0.91	52	52
SHC1	0.017	0.023	-10000	0	-0.52	1	1
ErbB4/EGFR/neuregulin 4	-0.13	0.31	-10000	0	-0.85	63	63
apoptosis	0.097	0.28	0.82	57	-10000	0	57
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.11	0.31	-10000	0	-0.92	55	55
ErbB4/ErbB2/epiregulin	-0.1	0.27	-10000	0	-0.78	59	59
ErbB4/ErbB4/betacellulin/betacellulin	-0.13	0.3	-10000	0	-0.86	62	62
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.088	0.29	-10000	0	-0.72	74	74
MDM2	-0.096	0.3	-10000	0	-0.92	52	52
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.062	0.25	-10000	0	-0.84	44	44
STAT5A	-0.072	0.27	-10000	0	-0.84	50	50
ErbB4/EGFR/neuregulin 1 beta	-0.11	0.28	-10000	0	-0.78	63	63
DLG4	0.018	0	-10000	0	-10000	0	0
GRB2/SHC	0.024	0.023	-10000	0	-0.37	1	1
E4ICDs/TAB2/NCoR1	-0.081	0.28	-10000	0	-0.93	47	47
STAT5A (dimer)	-0.11	0.26	-10000	0	-0.79	59	59
MAP3K7IP2	0.014	0.047	-10000	0	-0.52	4	4
STAT5B (dimer)	-0.068	0.27	-10000	0	-0.83	51	51
LRIG1	-0.032	0.15	-10000	0	-0.48	53	53
EREG	-0.024	0.11	-10000	0	-0.28	74	74
BTC	-0.05	0.17	-10000	0	-0.42	82	82
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.081	0.28	-10000	0	-0.89	50	50
ERBB4	-0.11	0.32	-10000	0	-1	52	52
STAT5B	0.016	0.026	-10000	0	-0.39	2	2
YAP1	-0.014	0.1	-10000	0	-0.71	6	6
GRB2	0.016	0.024	-10000	0	-0.25	4	4
ErbB4/ErbB2/neuregulin 4	-0.088	0.27	-10000	0	-0.83	52	52
glial cell differentiation	0.079	0.28	0.91	47	-10000	0	47
WWOX	-0.003	0.072	-10000	0	-0.25	40	40
cell proliferation	-0.1	0.27	-10000	0	-0.78	58	58

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	-0.008	0.11	-10000	0	-0.4	33	33
EPHB2	0.008	0.062	-10000	0	-0.32	16	16
EFNB1	0.017	0.051	-10000	0	-0.4	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.021	0.082	-10000	0	-0.37	7	7
Ephrin B2/EPHB1-2	-0.006	0.089	-10000	0	-0.28	34	34
neuron projection morphogenesis	-0.023	0.061	-10000	0	-0.34	8	8
Ephrin B1/EPHB1-2/Tiam1	0.015	0.087	-10000	0	-0.29	22	22
DNM1	0.013	0.047	-10000	0	-0.37	7	7
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.084	0.23	-10000	0	-0.55	95	95
YES1	-0.13	0.3	-10000	0	-0.84	81	81
Ephrin B1/EPHB1-2/NCK2	0.019	0.078	-10000	0	-0.27	18	18
PI3K	-0.081	0.24	-10000	0	-0.56	97	97
mol:GDP	0.013	0.086	-10000	0	-0.29	22	22
ITGA2B	0.016	0.02	-10000	0	-0.25	3	3
endothelial cell proliferation	-0.01	0.1	-10000	0	-0.33	40	40
FYN	-0.13	0.3	-10000	0	-0.82	82	82
MAP3K7	-0.084	0.23	-10000	0	-0.63	81	81
FGR	-0.11	0.3	-10000	0	-0.82	81	81
TIAM1	0.006	0.073	-10000	0	-0.44	13	13
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
RGS3	0.017	0.012	-10000	0	-0.25	1	1
cell adhesion	-0.069	0.22	-10000	0	-0.55	87	87
LYN	-0.12	0.3	-10000	0	-0.83	81	81
Ephrin B1/EPHB1-2/Src Family Kinases	-0.12	0.28	-10000	0	-0.77	81	81
Ephrin B1/EPHB1-2	-0.11	0.25	-10000	0	-0.68	81	81
SRC	-0.11	0.3	-10000	0	-0.82	81	81
ITGB3	0.002	0.075	-10000	0	-0.32	25	25
EPHB1	-0.022	0.1	-10000	0	-0.28	72	72
EPHB4	-0.013	0.12	-10000	0	-0.43	36	36
RAC1	0.018	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.01	0.1	-10000	0	-0.34	40	40
alphaIIb/beta3 Integrin	0.014	0.056	-10000	0	-0.36	7	7
BLK	-0.13	0.3	-10000	0	-0.83	81	81
HCK	-0.13	0.3	-10000	0	-0.82	82	82
regulation of stress fiber formation	-0.018	0.076	0.27	18	-10000	0	18
MAPK8	-0.074	0.22	-10000	0	-0.51	97	97
Ephrin B1/EPHB1-2/RGS3	0.02	0.075	-10000	0	-0.27	15	15
endothelial cell migration	-0.09	0.22	-10000	0	-0.47	114	114
NCK2	0.015	0.026	-10000	0	-0.25	5	5
PTPN13	-0.089	0.24	-10000	0	-0.59	93	93
regulation of focal adhesion formation	-0.018	0.076	0.27	18	-10000	0	18
chemotaxis	-0.019	0.074	0.27	15	-10000	0	15
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
Rac1/GTP	0.015	0.078	-10000	0	-0.36	7	7
angiogenesis	-0.11	0.24	-10000	0	-0.68	81	81
LCK	-0.14	0.31	-10000	0	-0.82	84	84

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	-0.029	0.15	-9999	-0.4	63	63
alphaM/beta2 Integrin/GPIbA	-0.011	0.11	-9999	-0.34	40	40
alphaM/beta2 Integrin/proMMP-9	-0.036	0.15	-9999	-0.36	80	80
PLAUR	-0.016	0.13	-9999	-0.47	37	37
HMGB1	0.011	0.021	-9999	-0.27	1	1
alphaM/beta2 Integrin/Talin	0	0.1	-9999	-0.36	30	30
AGER	0.01	0.031	-9999	-0.39	2	2
RAP1A	0.012	0.057	-9999	-0.52	6	6
SELPLG	-0.003	0.097	-9999	-0.43	24	24
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.012	0.13	-9999	-0.36	39	39
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.042	0.17	-9999	-0.51	60	60
CYR61	-0.042	0.16	-9999	-0.42	72	72
TLN1	0.017	0.023	-9999	-0.52	1	1
Rap1/GTP	-0.036	0.1	-9999	-0.42	25	25
RHOA	0.005	0.08	-9999	-0.52	12	12
P-selectin oligomer	-0.12	0.22	-9999	-0.44	156	156
MYH2	-0.003	0.13	-9999	-0.44	25	25
MST1R	-0.039	0.16	-9999	-0.51	57	57
leukocyte activation during inflammatory response	0.008	0.086	-9999	-0.31	30	30
APOB	0.018	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.032	0.15	-9999	-0.47	54	54
JAM3	-0.006	0.11	-9999	-0.5	24	24
GP1BA	-0.002	0.071	-9999	-0.25	39	39
alphaM/beta2 Integrin/CTGF	-0.031	0.14	-9999	-0.39	59	59
alphaM/beta2 Integrin	-0.008	0.13	-9999	-0.45	27	27
JAM3 homodimer	-0.006	0.11	-9999	-0.5	24	24
ICAM2	0.007	0.068	-9999	-0.4	13	13
ICAM1	-0.019	0.12	-9999	-0.39	47	47
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.008	0.13	-9999	-0.44	27	27
cell adhesion	-0.011	0.11	-9999	-0.34	40	40
NFKB1	-0.032	0.17	-9999	-0.38	76	76
THY1	-0.007	0.11	-9999	-0.5	25	25
RhoA/GDP	0.004	0.058	-9999	-0.38	12	12
Lipoprotein(a)	0.023	0.016	-9999	-0.31	1	1
alphaM/beta2 Integrin/LRP/tPA	-0.049	0.14	-9999	-0.32	93	93
IL6	-0.087	0.27	-9999	-0.69	75	75
ITGB2	-0.022	0.12	-9999	-0.43	40	40
elevation of cytosolic calcium ion concentration	-0.044	0.18	-9999	-0.41	82	82
alphaM/beta2 Integrin/JAM2/JAM3	-0.02	0.15	-9999	-0.38	64	64
JAM2	-0.019	0.13	-9999	-0.43	43	43
alphaM/beta2 Integrin/ICAM1	-0.028	0.16	-9999	-0.33	91	91
alphaM/beta2 Integrin/uPA/Plg	-0.027	0.14	-9999	-0.34	75	75
RhoA/GTP	-0.008	0.14	-9999	-0.44	30	30
positive regulation of phagocytosis	-0.007	0.16	-9999	-0.5	35	35
Ron/MSP	-0.017	0.12	-9999	-0.37	55	55
alphaM/beta2 Integrin/uPAR/uPA	-0.044	0.18	-9999	-0.41	82	82
alphaM/beta2 Integrin/uPAR	-0.019	0.14	-9999	-0.4	52	52
PLAU	-0.052	0.17	-9999	-0.43	83	83
PLAT	-0.093	0.19	-9999	-0.37	150	150
actin filament polymerization	-0.001	0.13	-9999	-0.42	25	25
MST1	0.016	0.02	-9999	-0.25	3	3
alphaM/beta2 Integrin/lipoprotein(a)	0.011	0.088	-9999	-0.31	30	30
TNF	-0.035	0.19	-9999	-0.64	29	29
RAP1B	0.013	0.044	-9999	-0.32	8	8
alphaM/beta2 Integrin/uPA	-0.041	0.15	-9999	-0.38	74	74
fibrinolysis	-0.028	0.14	-9999	-0.34	75	75
HCK	-0.005	0.11	-9999	-0.47	25	25
dendritic cell antigen processing and presentation	-0.008	0.13	-9999	-0.44	27	27
VTN	0.016	0.02	-9999	-0.25	3	3
alphaM/beta2 Integrin/CYR61	-0.035	0.14	-9999	-0.37	69	69
LPA	0.016	0.026	-9999	-0.39	2	2
LRP1	0.017	0.023	-9999	-0.52	1	1
cell migration	-0.051	0.18	-9999	-0.36	106	106
FN1	-0.048	0.17	-9999	-0.46	73	73
alphaM/beta2 Integrin/Thy1	-0.014	0.12	-9999	-0.37	48	48
MPO	0.008	0.05	-9999	-0.25	19	19
KNG1	0.017	0.017	-9999	-0.25	2	2
RAP1/GDP	0.017	0.044	-9999	-0.31	8	8
ROCK1	0	0.13	-9999	-0.44	25	25
ELA2	0.017	0.017	-9999	-0.25	2	2
PLG	0.016	0.033	-9999	-0.52	2	2
CTGF	-0.035	0.15	-9999	-0.42	63	63
alphaM/beta2 Integrin/Hck	-0.012	0.14	-9999	-0.43	41	41
ITGAM	0.002	0.071	-9999	-0.48	10	10
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.072	0.18	-9999	-0.35	131	131
HP	0.013	0.049	-9999	-0.43	6	6
leukocyte adhesion	-0.034	0.18	-9999	-0.54	43	43
SELP	-0.12	0.22	-9999	-0.44	156	156

×

LPA receptor mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.005	0.08	-9999	-0.24	48	48
NF kappa B1 p50/RelA/I kappa B alpha	0.003	0.086	-9999	-0.3	16	16
AP1	-0.092	0.14	-9999	-0.3	133	133
mol:PIP3	-0.067	0.11	-9999	-0.28	85	85
AKT1	0.007	0.11	-9999	-0.34	29	29
PTK2B	-0.009	0.064	-9999	-0.2	47	47
RHOA	-0.007	0.093	-9999	-0.41	17	17
PIK3CB	0.012	0.055	-9999	-0.44	7	7
mol:Ca2+	-0.025	0.094	-9999	-0.27	53	53
MAGI3	-0.014	0.12	-9999	-0.46	35	35
RELA	0.018	0	-9999	-10000	0	0
apoptosis	-0.004	0.067	-9999	-0.22	44	44
HRAS/GDP	0.009	0.036	-9999	-0.29	7	7
positive regulation of microtubule depolymerization	-0.045	0.12	-9999	-0.26	117	117
NF kappa B1 p50/RelA	-0.04	0.092	-9999	-0.32	28	28
endothelial cell migration	-0.036	0.18	-9999	-0.55	54	54
ADCY4	-0.005	0.11	-9999	-0.3	48	48
ADCY5	-0.014	0.11	-9999	-0.31	48	48
ADCY6	-0.004	0.1	-9999	-0.29	47	47
ADCY7	-0.007	0.11	-9999	-0.32	47	47
ADCY1	-0.003	0.1	-9999	-0.29	47	47
ADCY2	-0.025	0.12	-9999	-0.34	53	53
ADCY3	-0.006	0.1	-9999	-0.29	49	49
ADCY8	-0.005	0.1	-9999	-0.29	47	47
ADCY9	-0.01	0.11	-9999	-0.29	48	48
GSK3B	-0.002	0.061	-9999	-0.18	45	45
arachidonic acid secretion	0.001	0.1	-9999	-0.28	49	49
GNG2	0.016	0.029	-9999	-0.34	3	3
TRIP6	0	0.088	-9999	-0.4	23	23
GNAO1	-0.004	0.078	-9999	-0.24	48	48
HRAS	0.012	0.051	-9999	-0.41	7	7
NFKBIA	-0.014	0.091	-9999	-0.27	33	33
GAB1	0.006	0.074	-9999	-0.43	14	14
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0.006	0.15	-9999	-0.89	15	15
JUN	-0.034	0.15	-9999	-0.46	57	57
LPA/LPA2/NHERF2	-0.024	0.1	-9999	-0.31	52	52
TIAM1	-0.025	0.18	-9999	-1	15	15
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
mol:IP3	-0.025	0.095	-9999	-0.27	53	53
PLCB3	-0.016	0.094	-9999	-0.3	49	49
FOS	-0.11	0.2	-9999	-0.37	171	171
positive regulation of mitosis	0.001	0.1	-9999	-0.28	49	49
LPA/LPA1-2-3	-0.015	0.068	-9999	-0.21	54	54
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.017	0.012	-9999	-0.25	1	1
stress fiber formation	0.001	0.063	-9999	-0.19	45	45
GNAZ	-0.013	0.096	-9999	-0.28	55	55
EGFR/PI3K-beta/Gab1	-0.069	0.12	-9999	-0.3	85	85
positive regulation of dendritic cell cytokine production	-0.015	0.068	-9999	-0.21	54	54
LPA/LPA2/MAGI-3	-0.013	0.08	-9999	-0.28	35	35
ARHGEF1	0.009	0.074	-9999	-0.21	46	46
GNAI2	-0.01	0.095	-9999	-0.29	49	49
GNAI3	-0.003	0.077	-9999	-0.25	44	44
GNAI1	-0.023	0.11	-9999	-0.31	58	58
LPA/LPA3	-0.011	0.033	-9999	-0.11	54	54
LPA/LPA2	-0.011	0.033	-9999	-0.1	54	54
LPA/LPA1	-0.019	0.09	-9999	-0.28	54	54
HB-EGF/EGFR	-0.069	0.16	-9999	-0.35	104	104
HBEGF	-0.027	0.13	-9999	-0.38	64	64
mol:DAG	-0.025	0.095	-9999	-0.27	53	53
cAMP biosynthetic process	-0.007	0.11	-9999	-0.3	51	51
NFKB1	0.017	0.023	-9999	-0.52	1	1
SRC	0.015	0.035	-9999	-0.43	3	3
GNB1	0.013	0.052	-9999	-0.52	5	5
LYN	-0.013	0.088	-9999	-0.27	29	29
GNAQ	-0.005	0.027	-9999	-0.082	54	54
LPAR2	0	0.001	-9999	-10000	0	0
LPAR3	0	0.001	-9999	-10000	0	0
LPAR1	-0.012	0.052	-9999	-0.16	54	54
IL8	-0.13	0.19	-9999	-0.42	120	120
PTK2	-0.003	0.067	-9999	-0.21	45	45
Rac1/GDP	0.013	0	-9999	-10000	0	0
CASP3	-0.004	0.068	-9999	-0.22	44	44
EGFR	-0.079	0.18	-9999	-0.35	139	139
PLCG1	-0.014	0.056	-9999	-0.14	66	66
PLD2	-0.004	0.071	-9999	-0.22	47	47
G12/G13	0.005	0.08	-9999	-0.24	46	46
PI3K-beta	-0.039	0.098	-9999	-0.36	30	30
cell migration	0.016	0.062	-9999	-0.25	17	17
SLC9A3R2	-0.032	0.15	-9999	-0.49	52	52
PXN	0.001	0.064	-9999	-0.2	45	45
HRAS/GTP	0.001	0.1	-9999	-0.28	49	49
RAC1	0.018	0	-9999	-10000	0	0
MMP9	-0.042	0.17	-9999	-0.51	60	60
PRKCE	0.01	0.061	-9999	-0.43	9	9
PRKCD	-0.019	0.094	-9999	-0.26	54	54
Gi(beta/gamma)	0	0.11	-9999	-0.29	48	48
mol:LPA	-0.012	0.052	-9999	-0.16	54	54
TRIP6/p130 Cas/FAK1/Paxillin	0.012	0.086	-9999	-0.33	14	14
MAPKKK cascade	0.001	0.1	-9999	-0.28	49	49
contractile ring contraction involved in cytokinesis	-0.007	0.092	-9999	-0.4	17	17
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.043	0.096	-9999	-0.29	56	56
GNA15	-0.003	0.051	-9999	-0.27	11	11
GNA12	0.018	0	-9999	-10000	0	0
GNA13	0.011	0.055	-9999	-0.36	10	10
MAPT	-0.047	0.13	-9999	-0.27	117	117
GNA11	0.002	0.038	-9999	-0.3	4	4
Rac1/GTP	0.005	0.16	-9999	-0.94	15	15
MMP2	-0.036	0.18	-9999	-0.55	54	54

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.042	0.15	-9999	-0.38	76	76
EPHB2	0.007	0.061	-9999	-0.32	16	16
Syndecan-2/TACI	-0.006	0.092	-9999	-0.3	38	38
LAMA1	0.015	0.026	-9999	-0.25	5	5
Syndecan-2/alpha2 ITGB1	-0.062	0.17	-9999	-0.31	143	143
HRAS	0.012	0.051	-9999	-0.41	7	7
Syndecan-2/CASK	-0.016	0.089	-9999	-0.31	38	38
ITGA5	0.015	0.035	-9999	-0.43	3	3
BAX	0.01	0.085	-9999	-10000	0	0
EPB41	0.016	0.026	-9999	-0.39	2	2
positive regulation of cell-cell adhesion	-0.011	0.094	-9999	-0.28	49	49
LAMA3	-0.07	0.19	-9999	-0.43	103	103
EZR	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.019	0.12	-9999	-0.39	48	48
Syndecan-2/MMP2	-0.033	0.14	-9999	-0.38	65	65
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.024	0.13	-9999	-0.37	58	58
dendrite morphogenesis	-0.009	0.095	-9999	-0.3	42	42
Syndecan-2/GM-CSF	-0.014	0.099	-9999	-0.31	43	43
determination of left/right symmetry	-0.017	0.11	-9999	-0.27	70	70
Syndecan-2/PKC delta	-0.006	0.094	-9999	-0.3	41	41
GNB2L1	0.015	0.04	-9999	-0.52	3	3
MAPK3	-0.005	0.09	-9999	-0.27	44	44
MAPK1	-0.005	0.092	-9999	-0.28	44	44
Syndecan-2/RACK1	0.004	0.087	-9999	-0.26	44	44
NF1	0.015	0.035	-9999	-0.43	3	3
FGFR/FGF/Syndecan-2	-0.017	0.11	-9999	-0.27	70	70
ITGA2	-0.048	0.17	-9999	-0.46	73	73
MAPK8	0.001	0.094	-9999	-0.3	41	41
Syndecan-2/alpha2/beta1 Integrin	-0.018	0.13	-9999	-0.3	86	86
Syndecan-2/Kininogen	-0.004	0.091	-9999	-0.3	38	38
ITGB1	0.014	0.044	-9999	-0.41	5	5
SRC	0.007	0.085	-9999	-0.25	45	45
Syndecan-2/CASK/Protein 4.1	-0.004	0.083	-9999	-0.27	39	39
extracellular matrix organization	-0.004	0.091	-9999	-0.3	39	39
actin cytoskeleton reorganization	-0.042	0.15	-9999	-0.38	76	76
Syndecan-2/Caveolin-2/Ras	-0.014	0.12	-9999	-0.33	55	55
Syndecan-2/Laminin alpha3	-0.055	0.15	-9999	-0.34	99	99
Syndecan-2/RasGAP	0.006	0.094	-9999	-0.25	52	52
alpha5/beta1 Integrin	0.022	0.041	-9999	-0.37	5	5
PRKCD	0.014	0.042	-9999	-0.45	4	4
Syndecan-2 dimer	-0.009	0.096	-9999	-0.3	42	42
GO:0007205	0.004	0.005	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.012	0.094	-9999	-0.24	53	53
RHOA	0.005	0.08	-9999	-0.52	12	12
SDCBP	0.003	0.081	-9999	-0.4	19	19
TNFRSF13B	0.013	0.035	-9999	-0.25	9	9
RASA1	0.004	0.078	-9999	-0.42	16	16
alpha2/beta1 Integrin	-0.024	0.13	-9999	-0.37	58	58
Syndecan-2/Synbindin	-0.003	0.091	-9999	-0.3	38	38
TGFB1	0.017	0.023	-9999	-0.52	1	1
CASP3	0.003	0.085	-9999	-0.27	41	41
FN1	-0.048	0.17	-9999	-0.46	73	73
Syndecan-2/IL8	-0.055	0.14	-9999	-0.33	87	87
SDC2	-0.017	0.11	-9999	-0.27	70	70
KNG1	0.017	0.017	-9999	-0.25	2	2
Syndecan-2/Neurofibromin	-0.005	0.093	-9999	-0.3	40	40
TRAPPC4	0.018	0	-9999	-10000	0	0
CSF2	-0.001	0.074	-9999	-0.28	33	33
Syndecan-2/TGFB1	-0.004	0.092	-9999	-0.3	39	39
Syndecan-2/Syntenin/PI-4-5-P2	-0.011	0.094	-9999	-0.28	49	49
Syndecan-2/Ezrin	-0.01	0.092	-9999	-0.28	50	50
PRKACA	0.004	0.084	-9999	-0.27	40	40
angiogenesis	-0.055	0.14	-9999	-0.33	87	87
MMP2	-0.032	0.15	-9999	-0.47	54	54
IL8	-0.072	0.17	-9999	-0.34	135	135
calcineurin-NFAT signaling pathway	-0.006	0.092	-9999	-0.3	38	38

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.005	0.13	-10000	0	-0.54	6	6
UGCG	-0.11	0.27	-10000	0	-0.77	74	74
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.07	0.19	-10000	0	-0.38	100	100
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.11	0.27	-10000	0	-0.76	74	74
mol:DAG	-0.014	0.12	-10000	0	-0.95	8	8
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.14	0.2	-10000	0	-0.42	149	149
FRAP1	-0.12	0.26	-10000	0	-0.47	159	159
FOXO3	-0.064	0.19	-10000	0	-0.42	77	77
AKT1	-0.073	0.21	-10000	0	-0.44	89	89
GAB2	0.007	0.048	-10000	0	-0.25	17	17
SMPD1	-0.004	0.079	-10000	0	-0.8	4	4
SGMS1	-0.01	0.099	-10000	0	-0.73	8	8
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	0.069	-10000	0	-0.31	21	21
CALM1	0.018	0	-10000	0	-10000	0	0
cell proliferation	-0.088	0.2	-10000	0	-0.45	103	103
EIF3A	0.017	0.012	-10000	0	-0.25	1	1
PI3K	0.006	0.083	-10000	0	-0.37	21	21
RPS6KB1	-0.034	0.1	-10000	0	-0.37	1	1
mol:sphingomyelin	-0.014	0.12	-10000	0	-0.95	8	8
natural killer cell activation	-0.002	0.004	-10000	0	-0.013	28	28
JAK3	0.018	0.004	-10000	0	-10000	0	0
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
JAK1	0.012	0.057	-10000	0	-0.52	6	6
NFKB1	0.017	0.023	-10000	0	-0.52	1	1
MYC	-0.091	0.28	-10000	0	-0.96	37	37
MYB	-0.23	0.5	-10000	0	-1.2	108	108
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.043	0.16	-10000	0	-0.37	59	59
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.014	0.099	-10000	0	-0.46	2	2
mol:PI-3-4-5-P3	-0.042	0.16	-10000	0	-0.37	59	59
Rac1/GDP	0.011	0.064	-10000	0	-0.28	21	21
T cell proliferation	-0.038	0.15	-10000	0	-0.34	59	59
SHC1	0.015	0.024	-10000	0	-0.52	1	1
RAC1	0.017	0.001	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.009	0.029	-10000	0	-0.061	118	118
PRKCZ	-0.04	0.15	-10000	0	-0.36	59	59
NF kappa B1 p50/RelA	-0.085	0.23	-10000	0	-0.46	108	108
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.016	0.14	-10000	0	-0.49	28	28
HSP90AA1	0.013	0.045	-10000	0	-0.39	6	6
RELA	0.018	0	-10000	0	-10000	0	0
IL2RA	-0.032	0.14	-10000	0	-0.41	60	60
IL2RB	-0.016	0.12	-10000	0	-0.43	40	40
TERT	0.013	0.042	-10000	0	-0.33	7	7
E2F1	-0.076	0.19	-10000	0	-0.44	113	113
SOS1	0.015	0.024	-10000	0	-0.53	1	1
RPS6	0.015	0.037	-10000	0	-0.39	4	4
mol:cAMP	0.004	0.014	0.029	119	-10000	0	119
PTPN11	0.015	0.024	-10000	0	-0.52	1	1
IL2RG	-0.002	0.078	-10000	0	-0.28	35	35
actin cytoskeleton organization	-0.038	0.15	-10000	0	-0.34	59	59
GRB2	0.014	0.024	-10000	0	-0.25	4	4
IL2	0.011	0.051	-10000	0	-0.33	10	10
PIK3CA	0.016	0.03	-10000	0	-0.35	3	3
Rac1/GTP	0.013	0.064	-10000	0	-0.26	21	21
LCK	-0.073	0.18	-10000	0	-0.4	117	117
BCL2	-0.19	0.39	-10000	0	-0.83	129	129

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.061	0.16	-10000	0	-0.39	72	72
IKBKB	0.005	0.077	-10000	0	-0.26	9	9
AKT1	-0.017	0.098	0.21	10	-0.22	55	65
IKBKG	0.008	0.078	-10000	0	-0.26	10	10
CALM1	-0.03	0.13	0.21	11	-0.36	46	57
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
MAP3K1	-0.075	0.19	-10000	0	-0.47	69	69
MAP3K7	0.016	0.02	-10000	0	-0.25	3	3
mol:Ca2+	-0.039	0.14	0.21	11	-0.37	51	62
DOK1	0.002	0.083	-10000	0	-0.41	19	19
AP-1	-0.045	0.1	0.18	1	-0.23	75	76
LYN	0.014	0.031	-10000	0	-0.25	7	7
BLNK	-0.012	0.12	-10000	0	-0.51	30	30
SHC1	0.017	0.023	-10000	0	-0.52	1	1
BCR complex	-0.033	0.13	-10000	0	-0.34	71	71
CD22	-0.055	0.19	-10000	0	-0.48	63	63
CAMK2G	-0.022	0.12	-10000	0	-0.33	45	45
CSNK2A1	0.017	0.023	-10000	0	-0.52	1	1
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.057	0.11	-10000	0	-0.44	21	21
GO:0007205	-0.04	0.14	0.21	11	-0.38	51	62
SYK	-0.023	0.14	-10000	0	-0.48	43	43
ELK1	-0.032	0.13	0.21	11	-0.36	49	60
NFATC1	-0.04	0.16	-10000	0	-0.38	64	64
B-cell antigen/BCR complex	-0.033	0.13	-10000	0	-0.34	71	71
PAG1/CSK	0.009	0.074	-10000	0	-0.37	16	16
NFKBIB	0.014	0.031	0.097	1	-0.12	2	3
HRAS	-0.028	0.13	-10000	0	-0.34	50	50
NFKBIA	0.015	0.03	0.097	1	-0.13	1	2
NF-kappa-B/RelA/I kappa B beta	0.02	0.027	-10000	0	-0.16	1	1
RasGAP/Csk	-0.026	0.14	-10000	0	-0.31	77	77
mol:GDP	-0.038	0.13	0.21	11	-0.36	51	62
PTEN	-0.002	0.1	-10000	0	-0.52	19	19
CD79B	-0.042	0.15	-10000	0	-0.36	84	84
NF-kappa-B/RelA/I kappa B alpha	0.02	0.027	-10000	0	-0.16	1	1
GRB2	0.016	0.024	-10000	0	-0.25	4	4
PI3K/BCAP/CD19	-0.063	0.18	-10000	0	-0.48	60	60
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
mol:IP3	-0.041	0.14	0.21	11	-0.38	51	62
CSK	0.015	0.031	-10000	0	-0.32	4	4
FOS	-0.078	0.15	-10000	0	-0.39	64	64
CHUK	0.001	0.094	-10000	0	-0.32	21	21
IBTK	0.016	0.033	-10000	0	-0.52	2	2
CARD11/BCL10/MALT1/TAK1	-0.023	0.12	0.2	1	-0.37	37	38
PTPN6	-0.046	0.18	-10000	0	-0.45	64	64
RELA	0.018	0	-10000	0	-10000	0	0
BCL2A1	0.013	0.03	-10000	0	-0.099	7	7
VAV2	-0.065	0.19	-10000	0	-0.51	60	60
ubiquitin-dependent protein catabolic process	0.019	0.03	0.1	1	-0.11	2	3
BTK	-0.036	0.2	-10000	0	-1.1	18	18
CD19	-0.073	0.2	-10000	0	-0.44	91	91
MAP4K1	0.012	0.04	-10000	0	-0.25	12	12
CD72	-0.03	0.14	-10000	0	-0.37	65	65
PAG1	-0.005	0.097	-10000	0	-0.38	30	30
MAPK14	-0.057	0.16	-10000	0	-0.42	61	61
SH3BP5	-0.005	0.1	-10000	0	-0.44	26	26
PIK3AP1	-0.045	0.16	0.23	11	-0.41	60	71
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.055	0.19	-10000	0	-0.44	71	71
RAF1	-0.02	0.12	-10000	0	-0.31	49	49
RasGAP/p62DOK/SHIP	-0.036	0.15	-10000	0	-0.32	79	79
CD79A	-0.011	0.084	-10000	0	-0.26	54	54
re-entry into mitotic cell cycle	-0.045	0.1	0.17	2	-0.23	74	76
RASA1	0.004	0.078	-10000	0	-0.42	16	16
MAPK3	-0.003	0.1	-10000	0	-0.32	26	26
MAPK1	-0.003	0.1	-10000	0	-0.32	27	27
CD72/SHP1	-0.055	0.19	-10000	0	-0.51	61	61
NFKB1	0.017	0.023	-10000	0	-0.52	1	1
MAPK8	-0.058	0.17	-10000	0	-0.41	65	65
actin cytoskeleton organization	-0.049	0.17	-10000	0	-0.44	59	59
NF-kappa-B/RelA	0.043	0.054	0.19	1	-0.23	3	4
Calcineurin	-0.023	0.12	-10000	0	-0.36	39	39
PI3K	-0.087	0.14	-10000	0	-0.39	74	74
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.043	0.15	0.24	11	-0.41	51	62
SOS1	0.017	0.023	-10000	0	-0.52	1	1
Bam32/HPK1	-0.13	0.31	-10000	0	-0.75	96	96
DAPP1	-0.16	0.35	-10000	0	-0.86	95	95
cytokine secretion	-0.037	0.15	-10000	0	-0.35	64	64
mol:DAG	-0.041	0.14	0.21	11	-0.38	51	62
PLCG2	-0.017	0.11	-10000	0	-0.32	55	55
MAP2K1	-0.011	0.11	-10000	0	-0.35	28	28
B-cell antigen/BCR complex/FcgammaRIIB	-0.045	0.15	-10000	0	-0.32	106	106
mol:PI-3-4-5-P3	-0.058	0.11	0.25	13	-0.29	63	76
ETS1	-0.019	0.12	-10000	0	-0.36	36	36
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.031	0.15	-10000	0	-0.31	86	86
B-cell antigen/BCR complex/LYN	-0.077	0.18	-10000	0	-0.54	50	50
MALT1	0.011	0.053	-10000	0	-0.37	9	9
TRAF6	0.017	0.023	-10000	0	-0.52	1	1
RAC1	-0.053	0.18	-10000	0	-0.47	57	57
B-cell antigen/BCR complex/LYN/SYK	-0.053	0.19	-10000	0	-0.5	60	60
CARD11	-0.038	0.14	0.21	11	-0.37	55	66
FCGR2B	-0.031	0.15	-10000	0	-0.5	50	50
PPP3CA	0.006	0.073	-10000	0	-0.44	13	13
BCL10	0.017	0.012	-10000	0	-0.25	1	1
IKK complex	0.012	0.04	0.11	1	-0.11	8	9
PTPRC	-0.04	0.15	-10000	0	-0.41	71	71
PDPK1	-0.017	0.091	0.2	9	-0.2	55	64
PPP3CB	0.016	0.026	-10000	0	-0.39	2	2
PPP3CC	-0.001	0.098	-10000	0	-0.51	19	19
POU2F2	0.019	0.021	-10000	0	-0.098	1	1

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.002	0.11	0.2	9	-0.25	59	68
ACTA1	-0.03	0.14	0.24	8	-0.34	63	71
NUMA1	-0.005	0.11	0.22	3	-0.26	45	48
SPTAN1	-0.01	0.13	0.24	11	-0.32	55	66
LIMK1	-0.029	0.15	0.23	9	-0.33	78	87
BIRC3	-0.085	0.19	-10000	0	-0.41	128	128
BIRC2	0.016	0.02	-10000	0	-0.25	3	3
BAX	0.016	0.02	-10000	0	-0.25	3	3
CASP10	-0.042	0.13	-10000	0	-0.31	100	100
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	-0.003	0.12	0.2	9	-0.27	53	62
DIABLO	0.018	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.009	0.13	0.23	11	-0.32	55	66
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.01	0.063	-10000	0	-0.49	8	8
GSN	-0.019	0.14	0.23	9	-0.34	64	73
MADD	0.018	0	-10000	0	-10000	0	0
TFAP2A	-0.009	0.14	-10000	0	-0.56	27	27
BID	-0.022	0.089	-10000	0	-0.2	95	95
MAP3K1	-0.029	0.13	-10000	0	-0.42	41	41
TRADD	0.016	0.026	-10000	0	-0.39	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.022	0.041	-10000	0	-0.37	5	5
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.029	0.14	0.23	5	-0.33	69	74
CASP9	0.017	0.023	-10000	0	-0.52	1	1
DNA repair	-0.02	0.075	0.29	8	-0.19	37	45
neuron apoptosis	-0.026	0.17	-10000	0	-0.64	36	36
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.005	0.13	0.25	3	-0.3	52	55
APAF1	0.012	0.051	-10000	0	-0.41	7	7
CASP6	0.003	0.11	-10000	0	-0.7	7	7
TRAF2	0.014	0.042	-10000	0	-0.45	4	4
ICAD/CAD	-0.003	0.13	0.23	11	-0.31	55	66
CASP7	0.044	0.12	0.29	68	-0.4	11	79
KRT18	-0.071	0.21	-10000	0	-0.57	76	76
apoptosis	-0.005	0.13	0.26	8	-0.3	56	64
DFFA	-0.01	0.13	0.24	11	-0.32	55	66
DFFB	-0.01	0.13	0.24	11	-0.32	55	66
PARP1	0.02	0.075	0.19	37	-0.3	8	45
actin filament polymerization	0.026	0.14	0.33	62	-0.22	9	71
TNF	-0.004	0.094	-10000	0	-0.36	31	31
CYCS	-0.012	0.062	-10000	0	-0.15	42	42
SATB1	-0.019	0.13	-10000	0	-0.45	25	25
SLK	-0.01	0.13	0.24	11	-0.32	56	67
p15 BID/BAX	-0.011	0.081	-10000	0	-0.28	11	11
CASP2	0.011	0.089	-10000	0	-0.38	11	11
JNK cascade	0.029	0.13	0.42	41	-10000	0	41
CASP3	-0.017	0.14	0.25	11	-0.35	55	66
LMNB2	0.018	0.068	-10000	0	-0.29	7	7
RIPK1	0.017	0.023	-10000	0	-0.52	1	1
CASP4	-0.005	0.11	-10000	0	-0.49	24	24
Mammalian IAPs/DIABLO	-0.024	0.11	-10000	0	-0.28	76	76
negative regulation of DNA binding	-0.009	0.14	-10000	0	-0.56	27	27
stress fiber formation	-0.01	0.13	0.23	11	-0.32	56	67
GZMB	-0.058	0.16	-10000	0	-0.37	98	98
CASP1	-0.038	0.16	-10000	0	-0.42	60	60
LMNB1	-0.032	0.12	-10000	0	-0.29	36	36
APP	-0.027	0.17	-10000	0	-0.65	36	36
TNFRSF1A	0.016	0.033	-10000	0	-0.52	2	2
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.013	0	-10000	0	-10000	0	0
VIM	-0.009	0.13	0.26	8	-0.3	56	64
LMNA	0.014	0.076	-10000	0	-0.3	11	11
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.004	0.094	-10000	0	-0.41	11	11
LRDD	0.018	0	-10000	0	-10000	0	0
SREBF1	-0.036	0.15	0.24	10	-0.32	85	95
APAF-1/Caspase 9	0.014	0.068	-10000	0	-0.57	2	2
nuclear fragmentation during apoptosis	-0.005	0.11	0.22	3	-0.26	45	48
CFL2	-0.027	0.15	0.23	4	-0.34	62	66
GAS2	-0.035	0.15	0.24	10	-0.32	82	92
positive regulation of apoptosis	-0.002	0.08	-10000	0	-0.26	19	19
PRF1	-0.008	0.091	-10000	0	-0.3	43	43

×

TCGA08_p53

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
CDKN2A	-0.037	0.11	-10000	0	-0.23	108	108
TP53	-0.036	0.1	0.28	2	-0.36	37	39
Senescence	-0.036	0.1	0.28	2	-0.36	37	39
Apoptosis	-0.036	0.1	0.28	2	-0.36	37	39
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.028	0.072	0.24	31	-0.18	13	44
MDM4	0.013	0.044	-10000	0	-0.32	8	8

×

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	0.01	0.066	-10000	0	-0.52	8	8
Jak2/Leptin Receptor	-0.039	0.12	0.21	1	-0.34	50	51
PTP1B/AKT1	-0.043	0.12	0.29	2	-0.32	50	52
FYN	0.008	0.067	-10000	0	-0.41	12	12
p210 bcr-abl/PTP1B	-0.055	0.12	0.32	2	-0.32	63	65
EGFR	-0.085	0.18	-10000	0	-0.36	139	139
EGF/EGFR	-0.14	0.2	-10000	0	-0.37	193	193
CSF1	0.014	0.037	-10000	0	-0.29	7	7
AKT1	0.011	0.054	-10000	0	-0.38	9	9
INSR	0.015	0.037	-10000	0	-0.39	4	4
PTP1B/N-cadherin	-0.065	0.15	0.28	2	-0.35	74	76
Insulin Receptor/Insulin	-0.02	0.1	-10000	0	-0.33	25	25
HCK	-0.005	0.11	-10000	0	-0.47	25	25
CRK	0.016	0.033	-10000	0	-0.52	2	2
TYK2	-0.046	0.12	0.3	2	-0.32	55	57
EGF	-0.15	0.23	-10000	0	-0.43	193	193
YES1	0.007	0.07	-10000	0	-0.43	12	12
CAV1	-0.074	0.14	0.29	2	-0.36	65	67
TXN	0.013	0.017	-10000	0	-0.26	2	2
PTP1B/IRS1/GRB2	-0.067	0.15	-10000	0	-0.35	92	92
cell migration	0.055	0.12	0.32	63	-0.32	2	65
STAT3	0.014	0.041	-10000	0	-0.52	3	3
PRLR	-0.027	0.15	-10000	0	-0.49	50	50
ITGA2B	0.015	0.02	-10000	0	-0.25	3	3
CSF1R	0.017	0.017	-10000	0	-0.25	2	2
Prolactin Receptor/Prolactin	-0.002	0.12	-10000	0	-0.36	47	47
FGR	0.017	0.017	-10000	0	-0.25	2	2
PTP1B/p130 Cas	-0.044	0.12	0.28	2	-0.31	57	59
Crk/p130 Cas	-0.036	0.12	-10000	0	-0.3	56	56
DOK1	-0.039	0.13	0.3	2	-0.38	42	44
JAK2	-0.037	0.12	-10000	0	-0.32	52	52
Jak2/Leptin Receptor/Leptin	-0.069	0.13	-10000	0	-0.37	51	51
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
PTPN1	-0.056	0.12	0.32	2	-0.32	64	66
LYN	0.014	0.031	-10000	0	-0.25	7	7
CDH2	-0.027	0.13	-10000	0	-0.34	66	66
SRC	-0.005	0.07	-10000	0	-0.68	3	3
ITGB3	0.001	0.076	-10000	0	-0.32	25	25
CAT1/PTP1B	-0.085	0.17	0.25	2	-0.44	67	69
CAPN1	0.003	0.078	-10000	0	-0.44	15	15
CSK	0.015	0.031	-10000	0	-0.32	4	4
PI3K	-0.036	0.1	-10000	0	-0.33	36	36
mol:H2O2	-0.003	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.062	0.12	-10000	0	-0.38	39	39
negative regulation of transcription	-0.037	0.11	-10000	0	-0.32	52	52
FCGR2A	-0.003	0.099	-10000	0	-0.45	23	23
FER	0.013	0.027	-10000	0	-0.4	2	2
alphaIIb/beta3 Integrin	0.011	0.056	-10000	0	-0.37	7	7
BLK	-0.019	0.1	-10000	0	-0.29	63	63
Insulin Receptor/Insulin/Shc	0.032	0.032	-10000	0	-0.31	4	4
RHOA	0.004	0.081	-10000	0	-0.53	12	12
LEPR	-0.005	0.093	-10000	0	-0.34	34	34
BCAR1	0.017	0.012	-10000	0	-0.25	1	1
p210 bcr-abl/Grb2	0.016	0.023	-10000	0	-0.25	4	4
mol:NADPH	-0.003	0.004	-10000	0	-10000	0	0
TRPV6	-0.06	0.16	-10000	0	-0.43	57	57
PRL	0.018	0.033	-10000	0	-0.32	4	4
SOCS3	-0.005	0.17	-10000	0	-1.3	8	8
SPRY2	-0.036	0.15	-10000	0	-0.43	60	60
Insulin Receptor/Insulin/IRS1	-0.008	0.12	-10000	0	-0.32	62	62
CSF1/CSF1R	-0.037	0.12	-10000	0	-0.34	39	39
Ras protein signal transduction	0.029	0.039	-10000	0	-0.19	3	3
IRS1	-0.048	0.17	-10000	0	-0.49	68	68
INS	0.017	0.024	-10000	0	-0.53	1	1
LEP	-0.051	0.15	-10000	0	-0.34	101	101
STAT5B	-0.043	0.11	0.25	2	-0.28	64	66
STAT5A	-0.044	0.11	0.25	2	-0.28	65	67
GRB2	0.016	0.024	-10000	0	-0.25	4	4
PDGFB-D/PDGFRB	-0.048	0.13	0.28	2	-0.35	56	58
CSN2	0.02	0.1	-10000	0	-1.4	2	2
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
LAT	-0.025	0.12	-10000	0	-0.55	19	19
YBX1	0.007	0.072	-10000	0	-0.33	16	16
LCK	-0.074	0.18	-10000	0	-0.4	117	117
SHC1	0.017	0.023	-10000	0	-0.52	1	1
NOX4	-0.059	0.18	-10000	0	-0.49	78	78

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.01	0.064	-9999	-0.37	9	9
alphaV beta3 Integrin	-0.034	0.13	-9999	-0.33	62	62
PTK2	-0.008	0.14	-9999	-0.47	26	26
IGF1R	-0.083	0.2	-9999	-0.47	110	110
PI4KB	0.016	0.033	-9999	-0.52	2	2
MFGE8	-0.018	0.12	-9999	-0.36	50	50
SRC	0.015	0.035	-9999	-0.43	3	3
CDKN1B	-0.022	0.13	-9999	-0.49	29	29
VEGFA	0	0.075	-9999	-0.29	31	31
ILK	0.002	0.072	-9999	-0.75	2	2
ROCK1	0.018	0	-9999	-10000	0	0
AKT1	0.007	0.075	-9999	-0.45	6	6
PTK2B	0.012	0.091	-9999	-0.32	27	27
alphaV/beta3 Integrin/JAM-A	-0.014	0.12	-9999	-0.28	60	60
CBL	0.017	0.012	-9999	-0.25	1	1
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.01	0.087	-9999	-0.33	27	27
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.11	0.22	-9999	-0.39	169	169
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.021	0.086	-9999	-0.37	14	14
alphaV/beta3 Integrin/Syndecan-1	-0.02	0.13	-9999	-0.33	67	67
PI4KA	0.018	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.18	0.24	-9999	-0.53	131	131
PI4 Kinase	0.025	0.024	-9999	-0.37	2	2
PIK3CA	0.016	0.029	-9999	-0.34	3	3
alphaV/beta3 Integrin/Osteopontin	-0.082	0.16	-9999	-0.33	141	141
RPS6KB1	-0.15	0.23	-9999	-0.49	135	135
TLN1	0.017	0.023	-9999	-0.52	1	1
MAPK3	-0.092	0.22	-9999	-0.65	57	57
GPR124	0	0.095	-9999	-0.52	17	17
MAPK1	-0.092	0.22	-9999	-0.64	58	58
PXN	0.018	0	-9999	-10000	0	0
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
alphaV/beta3 Integrin/Tumstatin	0.011	0.087	-9999	-0.35	24	24
cell adhesion	-0.008	0.12	-9999	-0.42	24	24
ANGPTL3	0.011	0.056	-9999	-0.42	8	8
VEGFR2 homodimer/VEGFA homodimer/Src	0.021	0.059	-9999	-0.3	11	11
IGF-1R heterotetramer	-0.083	0.2	-9999	-0.47	110	110
Rac1/GDP	0.013	0	-9999	-10000	0	0
TGFBR2	0.013	0.049	-9999	-0.43	6	6
ITGB3	0.002	0.075	-9999	-0.32	25	25
IGF1	-0.1	0.2	-9999	-0.41	146	146
RAC1	0.018	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	0.004	0.11	-9999	-0.38	33	33
apoptosis	-0.002	0.099	-9999	-0.48	21	21
CD47	-0.005	0.11	-9999	-0.47	25	25
alphaV/beta3 Integrin/CD47	0	0.1	-9999	-0.32	42	42
VCL	0.016	0.029	-9999	-0.34	3	3
alphaV/beta3 Integrin/Del1	-0.066	0.17	-9999	-0.35	115	115
CSF1	0.014	0.037	-9999	-0.29	7	7
PIK3C2A	-0.003	0.096	-9999	-0.74	6	6
PI4 Kinase/Pyk2	-0.042	0.092	-9999	-0.4	18	18
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.013	0.099	-9999	-0.34	29	29
FAK1/Vinculin	0.004	0.11	-9999	-0.37	26	26
alphaV beta3/Integrin/ppsTEM5	0.004	0.11	-9999	-0.38	33	33
RHOA	0.005	0.08	-9999	-0.52	12	12
VTN	0.016	0.02	-9999	-0.25	3	3
BCAR1	0.017	0.012	-9999	-0.25	1	1
FGF2	-0.064	0.16	-9999	-0.34	122	122
F11R	-0.037	0.12	-9999	-0.37	41	41
alphaV/beta3 Integrin/Lactadherin	-0.006	0.12	-9999	-0.39	38	38
alphaV/beta3 Integrin/TGFBR2	0.011	0.089	-9999	-0.35	26	26
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.031	0.062	-9999	-0.27	19	19
HSP90AA1	0.013	0.045	-9999	-0.39	6	6
alphaV/beta3 Integrin/Talin	0.014	0.075	-9999	-0.31	23	23
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.048	0.17	-9999	-0.46	73	73
alphaV/beta3 Integrin/Pyk2	0.018	0.094	-9999	-0.32	27	27
SDC1	-0.038	0.16	-9999	-0.46	62	62
VAV3	-0.024	0.13	-9999	-0.27	102	102
PTPN11	0.017	0.023	-9999	-0.52	1	1
IRS1	-0.048	0.17	-9999	-0.49	68	68
FAK1/Paxillin	0.004	0.11	-9999	-0.37	25	25
cell migration	0.011	0.1	-9999	-0.34	23	23
ITGAV	-0.002	0.1	-9999	-0.48	21	21
PI3K	-0.016	0.12	-9999	-0.41	22	22
SPP1	-0.14	0.23	-9999	-0.43	188	188
KDR	0.013	0.052	-9999	-0.52	5	5
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	-0.002	0.099	-9999	-0.48	21	21
COL4A3	0.013	0.047	-9999	-0.37	7	7
angiogenesis	-0.081	0.22	-9999	-0.65	56	56
Rac1/GTP	-0.013	0.12	-9999	-0.42	11	11
EDIL3	-0.11	0.22	-9999	-0.44	152	152
cell proliferation	0.011	0.089	-9999	-0.34	26	26

×

Visual signal transduction: Rods

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.011	0.056	-9999	-0.42	8	8
GNAT1/GTP	0.01	0.035	-9999	-0.34	5	5
Metarhodopsin II/Arrestin	-0.045	0.12	-9999	-0.31	64	64
PDE6G/GNAT1/GTP	0.02	0.033	-9999	-0.31	4	4
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.013	0.048	-9999	-0.47	5	5
GRK1	0	0	-9999	-10000	0	0
CNG Channel	-0.082	0.12	-9999	-0.27	137	137
mol:Na +	-0.04	0.088	-9999	-0.43	14	14
mol:ADP	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.056	0.15	-9999	-0.34	96	96
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.002	0.11	-9999	-0.44	14	14
CNGB1	0.018	0	-9999	-10000	0	0
RDH5	-0.003	0.072	-9999	-0.25	40	40
SAG	-0.098	0.19	-9999	-0.36	162	162
mol:Ca2+	0.001	0.11	-9999	-0.39	17	17
Na + (4 Units)	-0.039	0.085	-9999	-0.38	17	17
RGS9	-0.033	0.13	-9999	-0.31	81	81
GNB1/GNGT1	-0.033	0.1	-9999	-0.37	18	18
GNAT1/GDP	-0.04	0.13	-9999	-0.29	99	99
GUCY2D	0.018	0	-9999	-10000	0	0
GNGT1	-0.063	0.14	-9999	-0.28	144	144
GUCY2F	0.006	0.076	-9999	-0.46	13	13
GNB5	0.005	0.081	-9999	-0.5	13	13
mol:GMP (4 units)	-0.034	0.12	-9999	-0.26	118	118
mol:11-cis-retinal	-0.003	0.072	-9999	-0.25	40	40
mol:cGMP	0.026	0.087	-9999	-0.3	30	30
GNB1	0.013	0.052	-9999	-0.52	5	5
Rhodopsin	0.012	0.049	-9999	-10000	0	0
SLC24A1	0.011	0.056	-9999	-0.42	8	8
CNGA1	-0.061	0.15	-9999	-0.32	123	123
Metarhodopsin II	0.011	0	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.027	0.075	-9999	-0.29	24	24
RGS9BP	-0.072	0.18	-9999	-0.41	111	111
Metarhodopsin II/Transducin	-0.005	0.064	-9999	-0.25	22	22
GCAP Family/Ca ++	0.016	0.074	-9999	-0.3	24	24
PDE6A/B	-0.066	0.17	-9999	-0.37	115	115
mol:Pi	-0.056	0.15	-9999	-0.34	96	96
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.014	0.083	-9999	-0.29	22	22
PDE6B	-0.1	0.22	-9999	-0.5	123	123
PDE6A	0.011	0.048	-9999	-0.3	11	11
PDE6G	0.016	0.024	-9999	-0.25	4	4
RHO	0.018	0	-9999	-10000	0	0
PDE6	-0.088	0.17	-9999	-0.41	63	63
GUCA1A	0.001	0.092	-9999	-0.48	18	18
GC2/GCAP Family	0.02	0.092	-9999	-0.32	30	30
GUCA1C	0.005	0.078	-9999	-0.43	15	15
GUCA1B	0.014	0.035	-9999	-0.3	6	6

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.035	0.05	0.22	3	-0.53	1	4
AES	0.033	0.037	0.2	1	-10000	0	1
FBXW11	0.015	0.035	-10000	0	-0.43	3	3
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.009	0.076	-10000	0	-0.36	19	19
SMAD4	0.009	0.067	-10000	0	-0.49	9	9
DKK2	-0.026	0.14	-10000	0	-0.42	52	52
TLE1	-0.017	0.16	0.2	2	-0.48	50	52
MACF1	0.016	0.026	-10000	0	-0.39	2	2
CTNNB1	-0.006	0.098	0.28	2	-0.36	13	15
WIF1	-0.024	0.098	-10000	0	-0.25	81	81
beta catenin/RanBP3	0.069	0.19	0.38	108	-0.46	2	110
KREMEN2	-0.19	0.23	-10000	0	-0.41	257	257
DKK1	-0.12	0.19	-10000	0	-0.34	199	199
beta catenin/beta TrCP1	0.005	0.096	0.3	1	-0.37	11	12
FZD1	0.003	0.082	-10000	0	-0.43	17	17
AXIN2	-0.097	0.33	-10000	0	-1.3	31	31
AXIN1	0.017	0.012	-10000	0	-0.25	1	1
RAN	0.018	0.012	-10000	0	-0.25	1	1
Axin1/APC/GSK3/beta catenin	0.034	0.036	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.017	0.16	-10000	0	-0.43	34	34
Axin1/APC/GSK3	0.049	0.042	0.25	3	-10000	0	3
Axin1/APC/GSK3/beta catenin/Macf1	0.037	0.067	-10000	0	-0.3	2	2
HNF1A	0.031	0.044	0.2	1	-0.24	3	4
CTBP1	0.033	0.041	0.21	2	-0.26	1	3
MYC	-0.12	0.36	-10000	0	-1.4	36	36
RANBP3	0.018	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.12	0.16	-10000	0	-0.33	186	186
NKD1	0.009	0.059	-10000	0	-0.38	11	11
TCF4	0.008	0.12	0.2	2	-0.49	26	28
TCF3	0.029	0.057	0.21	2	-0.36	5	7
WNT1/LRP6/FZD1/Axin1	0.031	0.062	-10000	0	-0.27	20	20
Ran/GTP	0.014	0.009	-10000	0	-0.17	1	1
CtBP/CBP/TCF/TLE1/AES	0.098	0.25	0.5	118	-0.48	8	126
LEF1	-0.007	0.13	0.18	16	-0.31	64	80
DVL1	0.045	0.042	-10000	0	-0.31	3	3
CSNK2A1	0.017	0.023	-10000	0	-0.52	1	1
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.038	0.17	-10000	0	-0.49	35	35
DKK1/LRP6/Kremen 2	-0.17	0.17	-10000	0	-0.33	249	249
LRP6	0.008	0.065	-10000	0	-0.38	13	13
CSNK1A1	0.035	0.048	0.21	4	-0.46	1	5
NLK	0.008	0.044	-10000	0	-0.28	11	11
CCND1	-0.25	0.54	-10000	0	-1.4	87	87
WNT1	0.016	0.023	-10000	0	-0.52	1	1
GSK3A	0.018	0.001	-10000	0	-10000	0	0
GSK3B	0.017	0.001	-10000	0	-10000	0	0
FRAT1	0.008	0.068	-10000	0	-0.47	10	10
PPP2R5D	0.028	0.035	0.25	6	-10000	0	6
APC	0.026	0.062	-10000	0	-0.24	23	23
WNT1/LRP6/FZD1	0.037	0.06	-10000	0	-0.24	10	10
CREBBP	0.032	0.051	0.21	2	-0.52	2	4

×

Calcium signaling in the CD4+ TCR 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
NFATC1	-0.002	0.077	-10000	0	-0.3	26	26
NFATC2	0.013	0.043	-10000	0	-0.3	5	5
NFATC3	0.015	0.03	-10000	0	-10000	0	0
CD40LG	-0.097	0.25	-10000	0	-0.55	86	86
PTGS2	-0.11	0.26	-10000	0	-0.56	87	87
JUNB	0.011	0.055	-10000	0	-0.36	10	10
CaM/Ca2+/Calcineurin A alpha-beta B1	0.008	0.018	-10000	0	-10000	0	0
CaM/Ca2+	0.008	0.018	-10000	0	-10000	0	0
CALM1	0.016	0.009	-10000	0	-10000	0	0
JUN	-0.035	0.15	-10000	0	-0.46	57	57
mol:Ca2+	-0.004	0.011	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.011	0.011	-10000	0	-0.14	2	2
FOSL1	0.016	0.024	-10000	0	-0.25	4	4
CREM	0.016	0.017	-10000	0	-0.26	2	2
Jun/NFAT1-c-4/p21SNFT	-0.024	0.15	-10000	0	-0.35	53	53
FOS	-0.11	0.2	-10000	0	-0.37	171	171
IFNG	-0.14	0.3	-10000	0	-0.6	113	113
AP-1/NFAT1-c-4	-0.1	0.3	-10000	0	-0.62	95	95
FASLG	-0.12	0.3	-10000	0	-0.62	108	108
NFAT1-c-4/ICER1	0.008	0.095	0.24	1	-0.31	14	15
IL2RA	-0.11	0.28	-10000	0	-0.58	97	97
FKBP12/FK506	0.012	0.011	-10000	0	-0.17	2	2
CSF2	-0.099	0.26	-10000	0	-0.55	90	90
JunB/Fra1/NFAT1-c-4	0.016	0.1	-10000	0	-0.31	18	18
IL4	-0.095	0.25	-10000	0	-0.54	86	86
IL2	-0.005	0.1	-10000	0	-1.3	3	3
IL3	0.008	0.021	-10000	0	-10000	0	0
FKBP1A	0.017	0.017	-10000	0	-0.25	2	2
BATF3	0	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.026	0	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.034	0.14	-9999	-0.33	76	76
MAP3K8	-0.038	0.15	-9999	-0.39	70	70
FOS	-0.014	0.092	-9999	-0.3	11	11
PRKCA	0.01	0.034	-9999	-0.26	8	8
PTPN7	0.006	0.049	-9999	-0.28	14	14
HRAS	0.011	0.051	-9999	-0.41	7	7
PRKCB	-0.003	0.007	-9999	-0.013	169	169
NRAS	0.004	0.076	-9999	-0.41	16	16
RAS family/GTP	0.013	0.064	-9999	-0.28	20	20
MAPK3	0.002	0.057	-9999	-0.45	2	2
MAP2K1	-0.005	0.064	-9999	-0.23	11	11
ELK1	0.01	0.038	-9999	-0.39	4	4
BRAF	0.004	0.057	-9999	-0.41	7	7
mol:GTP	-0.001	0.002	-9999	-0.004	170	170
MAPK1	0.001	0.06	-9999	-0.43	3	3
RAF1	0.011	0.028	-9999	-10000	0	0
KRAS	0.008	0.065	-9999	-0.44	10	10

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.024	0.14	-10000	0	-0.46	46	46
ANTXR2	0.002	0.09	-10000	0	-0.5	16	16
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.007	0.021	-10000	0	-0.074	44	44
monocyte activation	-0.022	0.12	-10000	0	-0.41	41	41
MAP2K2	0.007	0.06	-10000	0	-0.77	3	3
MAP2K1	0.005	0.021	-10000	0	-10000	0	0
MAP2K7	0.005	0.024	-10000	0	-0.27	1	1
MAP2K6	-0.009	0.063	-10000	0	-0.2	39	39
CYAA	-0.014	0.092	-10000	0	-0.3	44	44
MAP2K4	-0.006	0.056	-10000	0	-0.21	31	31
IL1B	-0.03	0.095	-10000	0	-0.25	68	68
Channel	-0.009	0.1	-10000	0	-0.32	44	44
NLRP1	0.002	0.036	-10000	0	-0.2	9	9
CALM1	0.018	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.007	0.027	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.007	0.021	0.074	44	-10000	0	44
MAPK3	0.005	0.024	-10000	0	-0.19	2	2
MAPK1	0.004	0.027	-10000	0	-0.27	2	2
PGR	-0.14	0.12	-10000	0	-0.2	365	365
PA/Cellular Receptors	-0.011	0.11	-10000	0	-0.35	44	44
apoptosis	-0.007	0.021	-10000	0	-0.074	44	44
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.008	0.094	-10000	0	-0.3	44	44
macrophage activation	0.011	0.028	-10000	0	-0.25	3	3
TNF	-0.004	0.094	-10000	0	-0.36	31	31
VCAM1	-0.022	0.12	-10000	0	-0.42	41	41
platelet activation	0.007	0.027	-10000	0	-10000	0	0
MAPKKK cascade	-0.001	0.034	0.12	18	-10000	0	18
IL18	-0.031	0.11	-10000	0	-0.28	70	70
negative regulation of macrophage activation	-0.007	0.021	-10000	0	-0.074	44	44
LEF	-0.007	0.021	-10000	0	-0.074	44	44
CASP1	-0.006	0.042	-10000	0	-0.098	60	60
mol:cAMP	0.007	0.027	-10000	0	-10000	0	0
necrosis	-0.007	0.021	-10000	0	-0.074	44	44
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.008	0.095	-10000	0	-0.3	44	44
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.045	0.14	-10000	0	-0.37	67	67
fibroblast growth factor receptor signaling pathway	-0.045	0.14	-10000	0	-0.36	67	67
LAMA1	0.015	0.026	-10000	0	-0.25	5	5
PRNP	0.006	0.073	-10000	0	-0.44	13	13
GPC1/SLIT2	-0.025	0.14	-10000	0	-0.39	60	60
SMAD2	0.012	0.084	-10000	0	-0.28	36	36
GPC1/PrPc/Cu2+	0.002	0.083	-10000	0	-0.33	30	30
GPC1/Laminin alpha1	0.007	0.082	-10000	0	-0.37	22	22
TDGF1	0.017	0.012	-10000	0	-0.25	1	1
CRIPTO/GPC1	0.009	0.08	-10000	0	-0.37	22	22
APP/GPC1	-0.025	0.13	-10000	0	-0.38	57	57
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.01	0.081	-10000	0	-0.31	30	30
FLT1	0.004	0.08	-10000	0	-0.45	15	15
GPC1/TGFB/TGFBR1/TGFBR2	0.009	0.093	-10000	0	-0.32	35	35
SERPINC1	0.007	0.054	-10000	0	-0.27	19	19
FYN	0.01	0.079	-10000	0	-0.31	29	29
FGR	0.015	0.068	-10000	0	-0.3	22	22
positive regulation of MAPKKK cascade	-0.012	0.12	-10000	0	-0.36	42	42
SLIT2	-0.029	0.15	-10000	0	-0.48	50	50
GPC1/NRG	0.002	0.089	-10000	0	-0.38	23	23
NRG1	0.008	0.053	-10000	0	-0.27	18	18
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.002	0.097	-10000	0	-0.32	37	37
LYN	0.014	0.071	-10000	0	-0.31	22	22
mol:Spermine	-0.005	0.079	-10000	0	-0.35	25	25
cell growth	-0.045	0.14	-10000	0	-0.36	67	67
BMP signaling pathway	0.006	0.11	0.49	25	-10000	0	25
SRC	0.015	0.073	-10000	0	-0.32	23	23
TGFBR1	0.003	0.082	-10000	0	-0.42	18	18
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.054	0.14	-10000	0	-0.3	122	122
GPC1	-0.006	0.11	-10000	0	-0.49	25	25
TGFBR1 (dimer)	0.003	0.082	-10000	0	-0.42	18	18
VEGFA	0	0.075	-10000	0	-0.29	31	31
BLK	-0.005	0.092	-10000	0	-0.33	30	30
HCK	0.002	0.095	-10000	0	-0.32	41	41
FGF2	-0.064	0.16	-10000	0	-0.34	122	122
FGFR1	-0.013	0.11	-10000	0	-0.35	44	44
VEGFR1 homodimer	0.004	0.08	-10000	0	-0.45	15	15
TGFBR2	0.013	0.049	-10000	0	-0.43	6	6
cell death	-0.025	0.13	-10000	0	-0.38	57	57
ATIII/GPC1	0.002	0.088	-10000	0	-0.38	23	23
PLA2G2A/GPC1	-0.041	0.12	-10000	0	-0.39	41	41
LCK	-0.039	0.13	-10000	0	-0.32	82	82
neuron differentiation	0.002	0.089	-10000	0	-0.38	23	23
PrPc/Cu2+	0.005	0.053	-10000	0	-0.31	13	13
APP	-0.029	0.14	-10000	0	-0.43	56	56
TGFBR2 (dimer)	0.013	0.049	-10000	0	-0.43	6	6

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.002	0.07	-9999	-0.28	28	28
Caspase 8 (4 units)	-0.034	0.14	-9999	-0.42	31	31
NEF	-0.014	0.042	-9999	-0.18	10	10
NFKBIA	-0.004	0.061	-9999	-0.52	4	4
BIRC3	-0.064	0.21	-9999	-0.55	74	74
CYCS	-0.04	0.14	-9999	-0.41	37	37
RIPK1	0.017	0.023	-9999	-0.52	1	1
CD247	-0.13	0.24	-9999	-0.47	153	153
MAP2K7	-0.023	0.13	-9999	-0.5	16	16
protein ubiquitination	0.018	0.095	-9999	-0.33	13	13
CRADD	0.01	0.063	-9999	-0.49	8	8
DAXX	0.017	0.012	-9999	-0.25	1	1
FAS	-0.024	0.13	-9999	-0.42	51	51
BID	-0.048	0.14	-9999	-0.42	40	40
NF-kappa-B/RelA/I kappa B alpha	-0.014	0.12	-9999	-0.27	76	76
TRADD	0.016	0.026	-9999	-0.39	2	2
MAP3K5	-0.022	0.13	-9999	-0.42	47	47
CFLAR	0.009	0.065	-9999	-0.44	10	10
FADD	0	0.067	-9999	-0.25	35	35
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.014	0.12	-9999	-0.27	76	76
MAPK8	-0.016	0.12	-9999	-0.5	14	14
APAF1	0.012	0.051	-9999	-0.41	7	7
TRAF1	0.013	0.04	-9999	-0.28	9	9
TRAF2	0.014	0.042	-9999	-0.45	4	4
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.052	0.15	-9999	-0.35	69	69
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.01	0.1	-9999	-0.37	15	15
CHUK	0.017	0.1	-9999	-0.36	13	13
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0	0.11	-9999	-0.29	55	55
TCRz/NEF	-0.11	0.21	-9999	-0.43	133	133
TNF	-0.004	0.094	-9999	-0.36	31	31
FASLG	-0.12	0.26	-9999	-0.5	133	133
NFKB1	-0.001	0.046	-9999	-0.52	1	1
TNFR1A/BAG4/TNF-alpha	0.012	0.074	-9999	-0.31	18	18
CASP6	-0.02	0.14	-9999	-0.55	18	18
CASP7	-0.072	0.23	-9999	-0.54	80	80
RELA	0	0.04	-9999	-10000	0	0
CASP2	0.018	0	-9999	-10000	0	0
CASP3	-0.066	0.22	-9999	-0.54	78	78
TNFRSF1A	0.016	0.033	-9999	-0.52	2	2
TNFR1A/BAG4	0.014	0.054	-9999	-0.37	5	5
CASP8	0.018	0	-9999	-10000	0	0
CASP9	0.017	0.023	-9999	-0.52	1	1
MAP3K14	0.015	0.1	-9999	-0.41	11	11
APAF-1/Caspase 9	-0.097	0.15	-9999	-0.4	86	86
BCL2	-0.066	0.15	-9999	-0.44	36	36

×

Glypican 2 network

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
MDK	-0.016	0.12	-9999	-0.37	46	46
GPC2	0	0	-9999	-10000	0	0
GPC2/Midkine	-0.011	0.083	-9999	-0.26	46	46
neuron projection morphogenesis	-0.011	0.083	-9999	-0.26	46	46

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.011	0.088	-10000	0	-0.29	23	23
adherens junction organization	-0.013	0.11	-10000	0	-0.25	78	78
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.019	0.11	-10000	0	-0.34	21	21
FMN1	-0.008	0.1	-10000	0	-0.24	78	78
mol:IP3	0.006	0.081	-10000	0	-0.33	6	6
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.008	0.11	-10000	0	-0.25	78	78
CTNNB1	0.002	0.09	-10000	0	-0.45	19	19
AKT1	0.007	0.092	-10000	0	-0.33	11	11
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.018	0.15	-10000	0	-0.38	76	76
CTNND1	0.016	0.029	-10000	0	-0.34	3	3
mol:PI-4-5-P2	0	0.1	-10000	0	-0.23	78	78
VASP	-0.007	0.11	-10000	0	-0.24	84	84
ZYX	-0.006	0.11	-10000	0	-0.36	13	13
JUB	-0.023	0.13	-10000	0	-0.29	50	50
EGFR(dimer)	-0.043	0.13	-10000	0	-0.35	32	32
E-cadherin/beta catenin-gamma catenin	-0.019	0.12	-10000	0	-0.3	78	78
mol:PI-3-4-5-P3	0.003	0.092	-10000	0	-0.26	28	28
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
PI3K	0.004	0.093	-10000	0	-0.26	28	28
FYN	0.015	0.085	-10000	0	-0.3	15	15
mol:Ca2+	0.006	0.08	-10000	0	-0.32	6	6
JUP	0.012	0.056	-10000	0	-0.42	8	8
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
mol:DAG	0.006	0.081	-10000	0	-0.33	6	6
CDH1	-0.049	0.17	-10000	0	-0.48	70	70
RhoA/GDP	-0.025	0.12	-10000	0	-0.35	28	28
establishment of polarity of embryonic epithelium	-0.006	0.11	-10000	0	-0.24	84	84
SRC	0.015	0.035	-10000	0	-0.43	3	3
RAC1	0.018	0	-10000	0	-10000	0	0
RHOA	0.005	0.08	-10000	0	-0.52	12	12
EGFR	-0.079	0.18	-10000	0	-0.35	139	139
CASR	0.012	0.078	-10000	0	-0.31	7	7
RhoA/GTP	0.008	0.086	-10000	0	-0.32	11	11
AKT2	0.009	0.087	-10000	0	-0.36	5	5
actin cable formation	-0.007	0.1	-10000	0	-0.23	84	84
apoptosis	-0.006	0.089	0.26	26	-10000	0	26
CTNNA1	0.017	0.024	-10000	0	-0.52	1	1
mol:GDP	-0.03	0.12	-10000	0	-0.36	22	22
PIP5K1A	-0.001	0.1	-10000	0	-0.23	78	78
PLCG1	0.006	0.082	-10000	0	-0.34	6	6
Rac1/GTP	-0.034	0.12	-10000	0	-0.32	31	31
homophilic cell adhesion	0	0.003	-10000	0	-10000	0	0

×

Coregulation of Androgen receptor activity

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.042	0.16	-9999	-0.46	67	67
SVIL	-0.004	0.1	-9999	-0.43	27	27
ZNF318	0.014	0.005	-9999	-10000	0	0
JMJD2C	0.023	0.032	-9999	-0.32	4	4
T-DHT/AR/Ubc9	-0.065	0.14	-9999	-0.33	103	103
CARM1	0.014	0.039	-9999	-0.36	5	5
PRDX1	0.012	0.05	-9999	-0.43	6	6
PELP1	0.017	0.001	-9999	-10000	0	0
CTNNB1	0.002	0.09	-9999	-0.45	19	19
AKT1	0.01	0.053	-9999	-0.37	9	9
PTK2B	0.017	0.017	-9999	-0.25	2	2
MED1	-0.001	0.066	-9999	-0.25	34	34
MAK	-0.018	0.094	-9999	-0.28	57	57
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.019	0.012	-9999	-0.25	1	1
GSN	0	0.095	-9999	-0.43	23	23
NCOA2	0.009	0.063	-9999	-0.4	11	11
NCOA6	0.019	0.012	-9999	-0.25	1	1
DNA-PK	0.029	0.029	-9999	-0.31	2	2
NCOA4	0.008	0.069	-9999	-0.45	11	11
PIAS3	0.019	0.002	-9999	-10000	0	0
cell proliferation	-0.043	0.092	-9999	-0.67	7	7
XRCC5	0.017	0.001	-9999	-10000	0	0
UBE3A	0.018	0.033	-9999	-0.52	2	2
T-DHT/AR/SNURF	-0.076	0.14	-9999	-0.32	118	118
FHL2	-0.15	0.34	-9999	-0.95	73	73
RANBP9	0.019	0.012	-9999	-0.25	1	1
JMJD1A	-0.002	0.055	-9999	-10000	0	0
CDK6	-0.019	0.1	-9999	-0.29	63	63
TGFB1I1	-0.003	0.1	-9999	-0.48	23	23
T-DHT/AR/CyclinD1	-0.12	0.21	-9999	-0.43	149	149
XRCC6	0.016	0.012	-9999	-0.26	1	1
T-DHT/AR	-0.085	0.17	-9999	-0.33	138	138
CTDSP1	0.016	0.033	-9999	-0.52	2	2
CTDSP2	0.011	0.044	-9999	-0.42	5	5
BRCA1	0.001	0.094	-9999	-0.48	19	19
TCF4	-0.01	0.12	-9999	-0.51	26	26
CDKN2A	-0.055	0.15	-9999	-0.33	108	108
SRF	0	0.054	-9999	-0.28	4	4
NKX3-1	-0.056	0.11	-9999	-0.25	97	97
KLK3	0.022	0.055	-9999	-10000	0	0
TMF1	0.018	0.001	-9999	-10000	0	0
HNRNPA1	0.015	0.023	-9999	-0.52	1	1
AOF2	0.018	0.026	-9999	-0.39	2	2
APPL1	0.015	0.054	-9999	-0.37	9	9
T-DHT/AR/Caspase 8	-0.066	0.14	-9999	-0.33	103	103
AR	-0.11	0.21	-9999	-0.53	104	104
UBA3	0	0.001	-9999	-10000	0	0
PATZ1	0.003	0.084	-9999	-0.5	14	14
PAWR	0.001	0.091	-9999	-0.44	20	20
PRKDC	0.011	0.045	-9999	-0.31	9	9
PA2G4	0.016	0.012	-9999	-0.26	1	1
UBE2I	0.018	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.059	0.13	-9999	-0.3	103	103
RPS6KA3	0.011	0.057	-9999	-0.34	12	12
T-DHT/AR/ARA70	-0.071	0.15	-9999	-0.34	109	109
LATS2	0.004	0.078	-9999	-0.48	13	13
T-DHT/AR/PRX1	-0.062	0.13	-9999	-0.31	106	106
Cyclin D3/CDK11 p58	0.013	0.008	-9999	-0.17	1	1
VAV3	-0.082	0.2	-9999	-0.48	108	108
KLK2	-0.013	0.075	-9999	-0.4	1	1
CASP8	0.017	0.001	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.054	0.14	-9999	-0.3	111	111
TMPRSS2	-0.18	0.38	-9999	-0.96	97	97
CCND1	-0.089	0.2	-9999	-0.44	124	124
PIAS1	0.019	0.012	-9999	-0.25	1	1
mol:T-DHT	-0.018	0.037	-9999	-0.077	130	130
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.016	0.05	-9999	-0.43	6	6
T-DHT/AR/CDK6	-0.085	0.17	-9999	-0.37	118	118
CMTM2	0.016	0.023	-9999	-0.52	1	1
SNURF	0	0	-9999	-10000	0	0
ZMIZ1	-0.003	0.049	-9999	-0.31	6	6
CCND3	0.017	0.012	-9999	-0.25	1	1
TGIF1	0.006	0.073	-9999	-0.52	10	10
FKBP4	0.013	0.055	-9999	-0.44	7	7

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.012	0.011	-9999	-0.17	2	2
PRKCZ	0	0	-9999	-10000	0	0
MAP3K7IP2	0.014	0.047	-9999	-0.52	4	4
ERC1	0.011	0.056	-9999	-0.42	8	8
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.024	0.11	-9999	-0.32	40	40
IRAK/TOLLIP	0.029	0.019	-9999	-0.23	1	1
IKBKB	0.012	0.047	-9999	-0.31	10	10
IKBKG	0.018	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.025	0.12	-9999	-0.36	46	46
IL1A	0.006	0.063	-9999	-0.31	18	18
IL1B	-0.067	0.18	-9999	-0.43	86	86
IRAK/TRAF6/p62/Atypical PKCs	0.031	0.053	-9999	-0.23	18	18
IL1R2	-0.045	0.15	-9999	-0.35	89	89
IL1R1	-0.046	0.16	-9999	-0.4	80	80
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.018	0.12	-9999	-0.29	61	61
TOLLIP	0.017	0.012	-9999	-0.25	1	1
TICAM2	0	0	-9999	-10000	0	0
MAP3K3	0.017	0.012	-9999	-0.25	1	1
TAK1/TAB1/TAB2	0.033	0.034	-9999	-0.34	4	4
IKK complex/ELKS	0.051	0.075	-9999	-0.45	3	3
JUN	0.014	0.093	-9999	-0.44	4	4
MAP3K7	0.016	0.02	-9999	-0.25	3	3
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.059	0.18	-9999	-0.34	120	120
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.002	0.1	-9999	-0.28	57	57
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.005	0.1	-9999	-0.26	57	57
IL1 beta fragment/IL1R1/IL1RAP	-0.069	0.18	-9999	-0.36	120	120
NFKB1	0.017	0.023	-9999	-0.52	1	1
MAPK8	0.032	0.063	-9999	-0.37	2	2
IRAK1	0.019	0.018	-9999	-10000	0	0
IL1RN/IL1R1	-0.061	0.17	-9999	-0.41	87	87
IRAK4	0.014	0.044	-9999	-0.41	5	5
PRKCI	0.002	0.085	-9999	-0.43	18	18
TRAF6	0.017	0.023	-9999	-0.52	1	1
PI3K	0.005	0.082	-9999	-0.37	21	21
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.032	0.13	-9999	-0.36	47	47
CHUK	0.005	0.081	-9999	-0.5	13	13
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.069	0.18	-9999	-0.36	120	120
IL1 beta/IL1R2	-0.082	0.18	-9999	-0.36	128	128
IRAK/TRAF6/TAK1/TAB1/TAB2	0.048	0.033	-9999	-0.33	1	1
NF kappa B1 p50/RelA	-0.082	0.14	-9999	-0.44	54	54
IRAK3	-0.018	0.099	-9999	-0.28	64	64
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.056	0.17	-9999	-0.34	110	110
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.004	0.089	-9999	-0.38	4	4
IL1 alpha/IL1R1/IL1RAP	-0.013	0.11	-9999	-0.31	53	53
RELA	0.018	0	-9999	-10000	0	0
MAP3K7IP1	0.018	0	-9999	-10000	0	0
SQSTM1	0.012	0.053	-9999	-0.48	6	6
MYD88	0.013	0.048	-9999	-0.47	5	5
IRAK/TRAF6/MEKK3	0.038	0.021	-9999	-0.25	1	1
IL1RAP	0.012	0.044	-9999	-0.28	11	11
UBE2N	0.017	0.017	-9999	-0.25	2	2
IRAK/TRAF6	-0.069	0.12	-9999	-0.39	49	49
CASP1	-0.051	0.17	-9999	-0.42	84	84
IL1RN/IL1R2	-0.06	0.16	-9999	-0.39	82	82
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.057	0.17	-9999	-0.35	111	111
TMEM189-UBE2V1	0	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.003	0.1	-9999	-0.3	50	50
PIK3CA	0.016	0.029	-9999	-0.34	3	3
IL1RN	-0.043	0.16	-9999	-0.4	76	76
TRAF6/TAK1/TAB1/TAB2	0.04	0.031	-9999	-0.26	5	5
MAP2K6	0.028	0.063	-9999	-0.24	24	24

×

Signaling mediated by p38-gamma and p38-delta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.018	0.062	-9999	-0.31	17	17
SNTA1	0.011	0.058	-9999	-0.48	7	7
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.004	0.086	-9999	-0.32	31	31
MAPK12	-0.004	0.092	-9999	-0.28	47	47
CCND1	-0.07	0.17	-9999	-0.42	91	91
p38 gamma/SNTA1	0.002	0.093	-9999	-0.26	51	51
MAP2K3	0.014	0.037	-9999	-0.29	7	7
PKN1	0.013	0.045	-9999	-0.39	6	6
G2/M transition checkpoint	-0.004	0.091	-9999	-0.27	47	47
MAP2K6	-0.005	0.091	-9999	-0.3	43	43
MAPT	-0.054	0.15	-9999	-0.32	120	120
MAPK13	0.011	0.071	-9999	-0.38	16	16
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.003	0.072	-9999	-0.33	23	23

×

Class IB PI3K non-lipid kinase 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
cAMP biosynthetic process	0.004	0.088	0.33	33	-10000	0	33
PI3K Class IB/PDE3B	-0.004	0.088	-10000	0	-0.33	33	33
PDE3B	-0.004	0.088	-10000	0	-0.33	33	33

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.019	0.049	-10000	0	-0.51	4	4
HSPA8	0.001	0.09	-10000	0	-0.52	15	15
SMAD3/SMAD4/ER alpha	-0.091	0.2	0.23	4	-0.37	158	162
AKT1	0.01	0.056	-10000	0	-0.37	9	9
GSC	-0.2	0.49	-10000	0	-1.4	77	77
NKX2-5	-0.018	0.093	-10000	0	-0.26	67	67
muscle cell differentiation	0.066	0.16	0.43	58	-10000	0	58
SMAD2-3/SMAD4/SP1	-0.006	0.18	-10000	0	-0.42	59	59
SMAD4	-0.015	0.1	-10000	0	-0.32	33	33
CBFB	0.015	0.037	-10000	0	-0.39	4	4
SAP18	0.017	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.014	0.075	-10000	0	-0.29	8	8
SMAD3/SMAD4/VDR	0.027	0.12	-10000	0	-0.37	25	25
MYC	-0.024	0.14	-10000	0	-0.45	46	46
CDKN2B	-0.047	0.3	-10000	0	-1.3	25	25
AP1	-0.068	0.23	-10000	0	-0.54	76	76
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.037	0.066	-10000	0	-0.28	2	2
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.004	0.12	-10000	0	-0.34	37	37
SP3	0.014	0.02	-10000	0	-10000	0	0
CREB1	0.017	0.023	-10000	0	-0.52	1	1
FOXH1	-0.001	0.042	-10000	0	-10000	0	0
SMAD3/SMAD4/GR	-0.004	0.13	-10000	0	-0.36	47	47
GATA3	-0.099	0.22	-10000	0	-0.5	124	124
SKI/SIN3/HDAC complex/NCoR1	0.042	0.037	-10000	0	-10000	0	0
MEF2C/TIF2	-0.028	0.17	-10000	0	-0.5	42	42
endothelial cell migration	0.018	0.24	1.3	16	-10000	0	16
MAX	0.018	0.009	-10000	0	-10000	0	0
RBBP7	0.01	0.051	-10000	0	-0.3	13	13
RBBP4	0.016	0.026	-10000	0	-0.39	2	2
RUNX2	0.013	0.049	-10000	0	-0.43	6	6
RUNX3	-0.062	0.18	-10000	0	-0.4	101	101
RUNX1	-0.027	0.14	-10000	0	-0.42	54	54
CTBP1	0.017	0.017	-10000	0	-0.25	2	2
NR3C1	-0.001	0.099	-10000	0	-0.51	19	19
VDR	-0.003	0.1	-10000	0	-0.51	21	21
CDKN1A	-0.03	0.27	-10000	0	-1.2	21	21
KAT2B	0.001	0.006	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.016	0.13	-10000	0	-0.3	61	61
DCP1A	0.017	0.023	-10000	0	-0.52	1	1
SKI	0.016	0.017	-10000	0	-0.25	2	2
SERPINE1	-0.019	0.24	-10000	0	-1.3	16	16
SMAD3/SMAD4/ATF2	0.006	0.11	-10000	0	-0.32	31	31
SMAD3/SMAD4/ATF3	-0.017	0.14	-10000	0	-0.35	57	57
SAP30	0.012	0.053	-10000	0	-0.48	6	6
Cbp/p300/PIAS3	0.047	0.053	-10000	0	-0.29	6	6
JUN	-0.07	0.22	-10000	0	-0.54	75	75
SMAD3/SMAD4/IRF7	0.002	0.13	-10000	0	-0.36	40	40
TFE3	0.018	0.026	-10000	0	-10000	0	0
COL1A2	-0.1	0.37	-10000	0	-1	72	72
mesenchymal cell differentiation	-0.003	0.11	0.36	32	-10000	0	32
DLX1	-0.009	0.081	-10000	0	-0.25	53	53
TCF3	0.013	0.044	-10000	0	-0.32	8	8
FOS	-0.11	0.2	-10000	0	-0.38	171	171
SMAD3/SMAD4/Max	0.008	0.11	-10000	0	-0.33	30	30
Cbp/p300/SNIP1	0.035	0.046	-10000	0	-0.3	9	9
ZBTB17	0.019	0.012	-10000	0	-10000	0	0
LAMC1	0.003	0.15	-10000	0	-0.53	30	30
TGIF2/HDAC complex/SMAD3/SMAD4	0.001	0.12	-10000	0	-0.35	35	35
IRF7	0.007	0.079	-10000	0	-0.49	12	12
ESR1	-0.15	0.24	-10000	0	-0.46	181	181
HNF4A	0.016	0.033	-10000	0	-0.52	2	2
MEF2C	-0.035	0.18	-10000	0	-0.51	45	45
SMAD2-3/SMAD4	-0.008	0.12	-10000	0	-0.33	44	44
Cbp/p300/Src-1	0.036	0.055	-10000	0	-0.28	12	12
IGHV3OR16-13	-0.017	0.039	-10000	0	-0.52	1	1
TGIF2/HDAC complex	0.009	0.066	-10000	0	-0.42	11	11
CREBBP	0.019	0.034	-10000	0	-0.51	2	2
SKIL	0.005	0.07	-10000	0	-0.34	19	19
HDAC1	0.016	0.023	-10000	0	-0.52	1	1
HDAC2	0.008	0.053	-10000	0	-0.29	15	15
SNIP1	0.014	0.041	-10000	0	-0.52	3	3
GCN5L2	0.018	0.044	-10000	0	-0.46	4	4
SMAD3/SMAD4/TFE3	0.014	0.12	-10000	0	-0.35	38	38
MSG1/HSC70	-0.019	0.097	-10000	0	-0.41	16	16
SMAD2	-0.002	0.051	-10000	0	-0.51	1	1
SMAD3	-0.004	0.1	-10000	0	-0.4	23	23
SMAD3/E2F4-5/DP1/p107/SMAD4	0.008	0.097	-10000	0	-0.29	28	28
SMAD2/SMAD2/SMAD4	-0.007	0.055	-10000	0	-0.28	11	11
NCOR1	0.015	0.033	-10000	0	-0.52	2	2
NCOA2	0.009	0.063	-10000	0	-0.4	11	11
NCOA1	0.012	0.057	-10000	0	-0.52	6	6
MYOD/E2A	-0.001	0.097	-10000	0	-0.37	31	31
SMAD2-3/SMAD4/SP1/MIZ-1	0.007	0.17	-10000	0	-0.4	54	54
IFNB1	0.005	0.13	-10000	0	-0.43	28	28
SMAD3/SMAD4/MEF2C	-0.027	0.2	-10000	0	-0.53	50	50
CITED1	-0.029	0.1	-10000	0	-0.26	89	89
SMAD2-3/SMAD4/ARC105	0.009	0.12	-10000	0	-0.33	28	28
RBL1	0.01	0.048	-10000	0	-0.27	14	14
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.001	0.15	-10000	0	-0.47	36	36
RUNX1-3/PEBPB2	-0.042	0.14	-10000	0	-0.34	86	86
SMAD7	-0.042	0.23	-10000	0	-0.57	56	56
MYC/MIZ-1	-0.003	0.1	-10000	0	-0.37	33	33
SMAD3/SMAD4	0.046	0.14	0.31	29	-0.4	15	44
IL10	-0.046	0.18	-10000	0	-0.39	78	78
PIASy/HDAC complex	0.009	0.051	-10000	0	-0.44	6	6
PIAS3	0.019	0.005	-10000	0	-10000	0	0
CDK2	0.015	0.048	-10000	0	-0.3	10	10
IL5	-0.047	0.18	-10000	0	-0.4	70	70
CDK4	0.019	0.029	-10000	0	-0.25	5	5
PIAS4	0.009	0.051	-10000	0	-0.44	6	6
ATF3	-0.02	0.13	-10000	0	-0.41	47	47
SMAD3/SMAD4/SP1	-0.01	0.18	-10000	0	-0.42	60	60
FOXG1	-0.007	0.083	-10000	0	-0.27	45	45
FOXO3	0.015	0.061	-10000	0	-0.4	8	8
FOXO1	0.007	0.081	-10000	0	-0.37	20	20
FOXO4	0.019	0.047	-10000	0	-0.37	5	5
heart looping	-0.034	0.17	-10000	0	-0.51	45	45
CEBPB	0.004	0.073	-10000	0	-0.34	20	20
SMAD3/SMAD4/DLX1	-0.01	0.12	-10000	0	-0.31	43	43
MYOD1	-0.015	0.13	-10000	0	-0.47	36	36
SMAD3/SMAD4/HNF4	0.005	0.11	-10000	0	-0.32	35	35
SMAD3/SMAD4/GATA3	-0.062	0.2	-10000	0	-0.38	127	127
SnoN/SIN3/HDAC complex/NCoR1	0.005	0.07	-10000	0	-0.34	19	19
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.036	0.17	-10000	0	-0.34	100	100
SMAD3/SMAD4/SP1-3	-0.001	0.19	-10000	0	-0.48	51	51
MED15	0.018	0	-10000	0	-10000	0	0
SP1	-0.002	0.069	-10000	0	-0.29	7	7
SIN3B	0.017	0.012	-10000	0	-0.25	1	1
SIN3A	0.017	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.02	0.15	-10000	0	-0.36	53	53
ITGB5	-0.032	0.23	-10000	0	-0.64	58	58
TGIF/SIN3/HDAC complex/CtBP	0.041	0.042	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.061	0.19	-10000	0	-0.39	117	117
AR	-0.088	0.21	-10000	0	-0.52	104	104
negative regulation of cell growth	-0.002	0.12	-10000	0	-0.37	31	31
SMAD3/SMAD4/MYOD	-0.016	0.13	-10000	0	-0.31	64	64
E2F5	-0.014	0.12	-10000	0	-0.39	41	41
E2F4	0.017	0.017	-10000	0	-0.25	2	2
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.01	0.11	-10000	0	-0.32	19	19
SMAD2-3/SMAD4/FOXO1-3a-4	0.005	0.13	-10000	0	-0.35	42	42
TFDP1	0.011	0.042	-10000	0	-0.25	13	13
SMAD3/SMAD4/AP1	-0.064	0.24	-10000	0	-0.55	75	75
SMAD3/SMAD4/RUNX2	0.003	0.12	-10000	0	-0.36	32	32
TGIF2	0.009	0.066	-10000	0	-0.42	11	11
TGIF1	0.008	0.073	-10000	0	-0.52	10	10
ATF2	0.018	0	-10000	0	-10000	0	0

×

Nectin adhesion 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.01	0.066	-9999	-0.52	8	8
alphaV beta3 Integrin	0.001	0.094	-9999	-0.4	22	22
PTK2	-0.001	0.15	-9999	-0.46	42	42
positive regulation of JNK cascade	-0.028	0.086	-9999	-0.31	43	43
CDC42/GDP	0.021	0.13	-9999	-0.42	41	41
Rac1/GDP	0.023	0.13	-9999	-0.41	41	41
RAP1B	0.013	0.044	-9999	-0.32	8	8
RAP1A	0.012	0.057	-9999	-0.52	6	6
CTNNB1	0.001	0.09	-9999	-0.45	19	19
CDC42/GTP	-0.033	0.11	-9999	-0.38	43	43
nectin-3/I-afadin	-0.016	0.12	-9999	-0.41	41	41
RAPGEF1	0.009	0.15	-9999	-0.47	41	41
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.001	0.17	-9999	-0.54	41	41
PDGFB-D/PDGFRB	0.01	0.066	-9999	-0.52	8	8
TLN1	0.004	0.099	-9999	-0.4	20	20
Rap1/GTP	-0.031	0.093	-9999	-0.33	42	42
IQGAP1	0.018	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.015	0.073	-9999	-0.28	28	28
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.016	0.12	-9999	-0.41	41	41
PVR	0.008	0.059	-9999	-0.33	14	14
Necl-5(dimer)	0.008	0.059	-9999	-0.33	14	14
mol:GDP	0.011	0.16	-9999	-0.51	41	41
MLLT4	-0.006	0.11	-9999	-0.46	26	26
PIK3CA	0.016	0.029	-9999	-0.34	3	3
PI3K	0.001	0.13	-9999	-0.32	59	59
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.007	0.082	-9999	-0.38	21	21
positive regulation of lamellipodium assembly	-0.028	0.088	-9999	-0.32	41	41
PVRL1	0.014	0.035	-9999	-0.3	6	6
PVRL3	-0.019	0.12	-9999	-0.4	46	46
PVRL2	0.002	0.089	-9999	-0.52	15	15
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
CDH1	-0.049	0.17	-9999	-0.48	70	70
CLDN1	-0.11	0.21	-9999	-0.4	165	165
JAM-A/CLDN1	-0.065	0.16	-9999	-0.32	128	128
SRC	-0.01	0.18	-9999	-0.61	41	41
ITGB3	0.002	0.075	-9999	-0.32	25	25
nectin-1(dimer)/I-afadin/I-afadin	0.007	0.082	-9999	-0.38	21	21
FARP2	0.006	0.16	-9999	-0.51	43	43
RAC1	0.018	0	-9999	-10000	0	0
CTNNA1	0.017	0.023	-9999	-0.52	1	1
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.006	0.11	-9999	-0.35	44	44
nectin-1/I-afadin	0.007	0.082	-9999	-0.38	21	21
nectin-2/I-afadin	-0.002	0.1	-9999	-0.39	33	33
RAC1/GTP/IQGAP1/filamentous actin	0.024	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.002	0.11	-9999	-0.34	43	43
CDC42/GTP/IQGAP1/filamentous actin	0.024	0	-9999	-10000	0	0
F11R	0.011	0.055	-9999	-0.36	10	10
positive regulation of filopodium formation	-0.028	0.086	-9999	-0.31	43	43
alphaV/beta3 Integrin/Talin	0.006	0.13	-9999	-0.48	20	20
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.002	0.1	-9999	-0.39	33	33
nectin-2(dimer)/I-afadin/I-afadin	-0.002	0.1	-9999	-0.39	33	33
PIP5K1C	-0.004	0.1	-9999	-0.42	21	21
VAV2	0.006	0.16	-9999	-0.52	41	41
RAP1/GDP	0.019	0.13	-9999	-0.39	41	41
ITGAV	-0.002	0.1	-9999	-0.48	21	21
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.01	0.12	-9999	-0.35	53	53
nectin-3(dimer)/I-afadin/I-afadin	-0.016	0.12	-9999	-0.41	41	41
Rac1/GTP	-0.032	0.11	-9999	-0.4	41	41
PTPRM	-0.011	0.11	-9999	-0.31	47	47
E-cadherin/beta catenin/alpha catenin	-0.012	0.13	-9999	-0.25	104	104
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.018	0	-9999	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.003	0.068	-9999	-0.28	26	26
Syndecan-3/Src/Cortactin	-0.046	0.16	-9999	-0.52	35	35
Syndecan-3/Neurocan	-0.007	0.13	-9999	-0.57	24	24
POMC	0.001	0.072	-9999	-0.28	30	30
EGFR	-0.079	0.18	-9999	-0.35	139	139
Syndecan-3/EGFR	-0.049	0.16	-9999	-0.39	68	68
AGRP	0.016	0.029	-9999	-0.34	3	3
NCSTN	0.017	0.023	-9999	-0.52	1	1
PSENEN	0.017	0.012	-9999	-0.25	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.001	0.093	-9999	-0.51	17	17
APH1A	0.003	0.067	-9999	-0.29	25	25
NCAN	0.007	0.053	-9999	-0.25	21	21
long-term memory	-0.003	0.13	-9999	-0.48	32	32
Syndecan-3/IL8	-0.045	0.16	-9999	-0.42	58	58
PSEN1	0.013	0.052	-9999	-0.52	5	5
Src/Cortactin	0.014	0.054	-9999	-0.37	5	5
FYN	0.008	0.067	-9999	-0.41	12	12
limb bud formation	-0.031	0.12	-9999	-0.59	24	24
MC4R	0.014	0.039	-9999	-0.36	5	5
SRC	0.015	0.035	-9999	-0.43	3	3
PTN	-0.099	0.19	-9999	-0.37	158	158
FGFR/FGF/Syndecan-3	-0.032	0.12	-9999	-0.6	24	24
neuron projection morphogenesis	-0.045	0.16	-9999	-0.47	40	40
Syndecan-3/AgRP	-0.003	0.13	-9999	-0.56	25	25
Syndecan-3/AgRP/MC4R	0.006	0.13	-9999	-0.53	26	26
Fyn/Cortactin	0.009	0.068	-9999	-0.38	10	10
SDC3	-0.032	0.13	-9999	-0.61	24	24
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.044	0.15	-9999	-0.41	58	58
IL8	-0.072	0.17	-9999	-0.34	135	135
Syndecan-3/Fyn/Cortactin	-0.003	0.13	-9999	-0.49	32	32
Syndecan-3/CASK	-0.03	0.12	-9999	-0.58	24	24
alpha-MSH/MC4R	0.012	0.057	-9999	-0.37	5	5
Gamma Secretase	0.033	0.069	-9999	-0.25	25	25

×

E-cadherin signaling in the nascent adherens junction

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.037	0.17	-9999	-0.45	74	74
KLHL20	-0.015	0.099	-9999	-0.26	21	21
CYFIP2	-0.042	0.16	-9999	-0.47	65	65
Rac1/GDP	0.006	0.11	-9999	-0.3	21	21
ENAH	-0.036	0.18	-9999	-0.45	76	76
AP1M1	0.017	0.023	-9999	-0.52	1	1
RAP1B	0.013	0.044	-9999	-0.32	8	8
RAP1A	0.012	0.057	-9999	-0.52	6	6
CTNNB1	0.001	0.09	-9999	-0.45	19	19
CDC42/GTP	-0.032	0.069	-9999	-0.3	10	10
ABI1/Sra1/Nap1	-0.042	0.054	-9999	-0.17	36	36
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.005	0.12	-9999	-0.28	79	79
RAPGEF1	-0.015	0.15	-9999	-0.38	74	74
CTNND1	0.016	0.029	-9999	-0.34	3	3
regulation of calcium-dependent cell-cell adhesion	-0.039	0.17	-9999	-0.46	74	74
CRK	-0.024	0.16	-9999	-0.41	75	75
E-cadherin/gamma catenin/alpha catenin	-0.01	0.12	-9999	-0.31	65	65
alphaE/beta7 Integrin	0.023	0.038	-9999	-0.37	5	5
IQGAP1	0.018	0	-9999	-10000	0	0
NCKAP1	0.015	0.031	-9999	-0.32	4	4
Rap1/GTP/I-afadin	0.014	0.073	-9999	-0.28	28	28
DLG1	-0.031	0.17	-9999	-0.44	74	74
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.028	0.055	-9999	-0.22	14	14
MLLT4	-0.006	0.11	-9999	-0.46	26	26
ARF6/GTP/NME1/Tiam1	0.023	0.052	-9999	-0.3	10	10
PI3K	-0.036	0.07	-9999	-0.29	13	13
ARF6	0.016	0.033	-9999	-0.52	2	2
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.027	0.13	-9999	-0.37	64	64
TIAM1	0.006	0.073	-9999	-0.44	13	13
E-cadherin(dimer)/Ca2+	-0.005	0.11	-9999	-0.26	76	76
AKT1	-0.022	0.043	-9999	-0.18	11	11
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
CDH1	-0.049	0.17	-9999	-0.48	70	70
RhoA/GDP	0.003	0.12	-9999	-0.32	27	27
actin cytoskeleton organization	-0.009	0.075	-9999	-0.19	21	21
CDC42/GDP	0.008	0.11	-9999	-0.29	22	22
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.007	0.09	-9999	-0.24	66	66
ITGB7	0.018	0	-9999	-10000	0	0
RAC1	0.018	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.005	0.11	-9999	-0.28	76	76
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.014	0.1	-9999	-0.27	75	75
mol:GDP	-0.004	0.13	-9999	-0.3	75	75
CDC42/GTP/IQGAP1	0.024	0	-9999	-10000	0	0
JUP	0.011	0.056	-9999	-0.42	8	8
p120 catenin/RhoA/GDP	0.002	0.12	-9999	-0.34	20	20
RAC1/GTP/IQGAP1	0.024	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.023	0.035	-9999	-0.37	4	4
RHOA	0.005	0.08	-9999	-0.52	12	12
CDC42	0.018	0	-9999	-10000	0	0
CTNNA1	0.017	0.023	-9999	-0.52	1	1
positive regulation of S phase of mitotic cell cycle	-0.027	0.094	-9999	-0.2	99	99
NME1	0.012	0.039	-9999	-0.25	11	11
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.033	0.17	-9999	-0.44	75	75
regulation of cell-cell adhesion	-0.029	0.061	-9999	-0.26	10	10
WASF2	-0.021	0.031	-9999	-0.2	1	1
Rap1/GTP	-0.038	0.08	-9999	-0.34	10	10
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.009	0.1	-9999	-0.25	70	70
CCND1	-0.035	0.12	-9999	-0.25	99	99
VAV2	-0.022	0.16	-9999	-0.4	74	74
RAP1/GDP	0.005	0.11	-9999	-0.36	9	9
adherens junction assembly	-0.031	0.17	-9999	-0.43	75	75
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.016	0.02	-9999	-0.25	3	3
PIP5K1C	0.014	0.042	-9999	-0.45	4	4
regulation of heterotypic cell-cell adhesion	0.006	0.11	-9999	-0.24	84	84
E-cadherin/beta catenin	-0.045	0.11	-9999	-0.35	61	61
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.033	0.17	-9999	-0.44	75	75
PIK3CA	0.016	0.029	-9999	-0.34	3	3
Rac1/GTP	-0.078	0.12	-9999	-0.42	27	27
E-cadherin/beta catenin/alpha catenin	-0.017	0.12	-9999	-0.31	75	75
ITGAE	0.013	0.052	-9999	-0.52	5	5
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.04	0.18	-9999	-0.47	74	74

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.025	0.076	-10000	0	-0.64	6	6
HDAC1	0.022	0.03	-10000	0	-0.53	1	1
AES	0.019	0.006	-10000	0	-10000	0	0
FBXW11	0.015	0.035	-10000	0	-0.43	3	3
DTX1	0.012	0.049	-10000	0	-0.34	9	9
LRP6/FZD1	0.009	0.076	-10000	0	-0.36	19	19
TLE1	-0.031	0.15	-10000	0	-0.45	56	56
AP1	-0.05	0.13	-10000	0	-0.3	82	82
NCSTN	0.017	0.023	-10000	0	-0.52	1	1
ADAM10	0.013	0.045	-10000	0	-0.39	6	6
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.041	0.13	-10000	0	-0.42	8	8
NICD/RBPSUH	0.027	0.076	-10000	0	-0.63	6	6
WIF1	-0.024	0.098	-10000	0	-0.25	81	81
NOTCH1	-0.003	0.077	-10000	0	-0.67	6	6
PSENEN	0.017	0.012	-10000	0	-0.25	1	1
KREMEN2	-0.19	0.23	-10000	0	-0.41	257	257
DKK1	-0.12	0.19	-10000	0	-0.34	199	199
beta catenin/beta TrCP1	0.004	0.084	0.24	4	-0.35	17	21
APH1B	0.001	0.093	-10000	0	-0.51	17	17
APH1A	0.003	0.067	-10000	0	-0.29	25	25
AXIN1	0.006	0.04	0.24	8	-0.24	2	10
CtBP/CBP/TCF1/TLE1/AES	0.036	0.1	0.29	5	-0.26	1	6
PSEN1	0.013	0.052	-10000	0	-0.52	5	5
FOS	-0.11	0.2	-10000	0	-0.37	171	171
JUN	-0.034	0.15	-10000	0	-0.46	57	57
MAP3K7	0.019	0.022	-10000	0	-0.26	3	3
CTNNB1	-0.005	0.084	0.23	7	-0.38	15	22
MAPK3	0.016	0.026	-10000	0	-0.39	2	2
DKK2/LRP6/Kremen 2	-0.12	0.16	-10000	0	-0.33	186	186
HNF1A	0.017	0.026	-10000	0	-0.24	5	5
CTBP1	0.018	0.018	-10000	0	-0.26	2	2
MYC	-0.086	0.34	-10000	0	-1.4	34	34
NKD1	0.01	0.059	-10000	0	-0.38	11	11
FZD1	0.003	0.082	-10000	0	-0.43	17	17
NOTCH1 precursor/Deltex homolog 1	0.024	0.085	-10000	0	-0.69	6	6
apoptosis	-0.05	0.12	-10000	0	-0.3	82	82
Delta 1/NOTCHprecursor	0.027	0.076	-10000	0	-0.63	6	6
DLL1	0.017	0.012	-10000	0	-0.25	1	1
PPARD	0.004	0.045	-10000	0	-10000	0	0
Gamma Secretase	0.031	0.069	-10000	0	-0.25	25	25
APC	0.002	0.055	0.24	7	-0.35	7	14
DVL1	0.022	0.038	-10000	0	-0.38	3	3
CSNK2A1	0.016	0.023	-10000	0	-0.52	1	1
MAP3K7IP1	0.02	0.008	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.17	0.17	-10000	0	-0.34	249	249
LRP6	0.008	0.065	-10000	0	-0.38	13	13
CSNK1A1	0.016	0.024	-10000	0	-0.52	1	1
NLK	0.032	0.03	-10000	0	-0.26	1	1
CCND1	-0.22	0.51	-10000	0	-1.4	87	87
WNT1	0.017	0.023	-10000	0	-0.52	1	1
Axin1/APC/beta catenin	0.017	0.074	0.28	4	-0.35	6	10
DKK2	-0.026	0.14	-10000	0	-0.42	52	52
NOTCH1 precursor/DVL1	0.036	0.077	-10000	0	-0.57	6	6
GSK3B	0.018	0.001	-10000	0	-10000	0	0
FRAT1	0.01	0.068	-10000	0	-0.47	10	10
NOTCH/Deltex homolog 1	0.022	0.085	-10000	0	-0.7	6	6
PPP2R5D	0.013	0.036	0.27	5	-10000	0	5
MAPK1	0.016	0.033	-10000	0	-0.52	2	2
WNT1/LRP6/FZD1	0.009	0.079	-10000	0	-0.27	23	23
RBPJ	0.018	0	-10000	0	-10000	0	0
CREBBP	0.013	0.035	-10000	0	-0.52	2	2

×

TRAIL signaling pathway

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
TNFSF10	-0.042	0.16	-10000	0	-0.46	67	67
positive regulation of NF-kappaB transcription factor activity	-0.019	0.12	-10000	0	-0.37	52	52
MAP2K4	-0.013	0.12	-10000	0	-0.4	23	23
IKBKB	0.012	0.047	-10000	0	-0.31	10	10
TNFRSF10B	0.005	0.079	-10000	0	-0.46	14	14
TNFRSF10A	-0.004	0.1	-10000	0	-0.47	24	24
SMPD1	-0.008	0.086	-10000	0	-0.23	58	58
IKBKG	0.018	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.015	0.031	-10000	0	-0.32	4	4
TRAIL/TRAILR2	-0.026	0.14	-10000	0	-0.4	57	57
TRAIL/TRAILR3	-0.032	0.13	-10000	0	-0.37	54	54
TRAIL/TRAILR1	-0.032	0.14	-10000	0	-0.4	64	64
TRAIL/TRAILR4	-0.019	0.12	-10000	0	-0.37	52	52
TRAIL/TRAILR1/DAP3/GTP	-0.013	0.12	-10000	0	-0.3	65	65
IKK complex	-0.028	0.082	-10000	0	-0.42	15	15
RIPK1	0.017	0.023	-10000	0	-0.52	1	1
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.012	0.019	-10000	0	-0.27	2	2
MAPK3	-0.019	0.12	-10000	0	-0.37	52	52
MAP3K1	-0.01	0.12	-10000	0	-0.4	23	23
TRAILR4 (trimer)	0.015	0.031	-10000	0	-0.32	4	4
TRADD	0.016	0.026	-10000	0	-0.39	2	2
TRAILR1 (trimer)	-0.004	0.1	-10000	0	-0.46	24	24
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.004	0.11	-10000	0	-0.43	13	13
CFLAR	0.009	0.065	-10000	0	-0.44	10	10
MAPK1	-0.02	0.12	-10000	0	-0.37	53	53
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.002	0.12	-10000	0	-0.29	64	64
mol:ceramide	-0.008	0.086	-10000	0	-0.23	58	58
FADD	0	0.067	-10000	0	-0.25	35	35
MAPK8	-0.007	0.12	-10000	0	-0.41	20	20
TRAF2	0.014	0.042	-10000	0	-0.45	4	4
TRAILR3 (trimer)	-0.004	0.075	-10000	0	-0.26	41	41
CHUK	0.005	0.081	-10000	0	-0.5	13	13
TRAIL/TRAILR1/FADD	-0.025	0.13	-10000	0	-0.34	65	65
DAP3	0.016	0.026	-10000	0	-0.39	2	2
CASP10	-0.05	0.12	0.26	1	-0.36	54	55
JNK cascade	-0.019	0.12	-10000	0	-0.37	52	52
TRAIL (trimer)	-0.042	0.16	-10000	0	-0.46	67	67
TNFRSF10C	-0.004	0.075	-10000	0	-0.26	41	41
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.011	0.12	-10000	0	-0.29	66	66
TRAIL/TRAILR2/FADD	-0.019	0.13	-10000	0	-0.34	58	58
cell death	-0.008	0.086	-10000	0	-0.23	58	58
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0	0.11	-10000	0	-0.46	11	11
TRAILR2 (trimer)	0.005	0.079	-10000	0	-0.46	14	14
CASP8	0.01	0.042	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.003	0.12	-10000	0	-0.29	56	56

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.025	0.13	-9999	-0.5	37	37
PDGF/PDGFRA/CRKL	-0.006	0.1	-9999	-0.37	36	36
positive regulation of JUN kinase activity	0.019	0.077	-9999	-0.26	34	34
CRKL	0.014	0.047	-9999	-0.52	4	4
PDGF/PDGFRA/Caveolin-3	-0.004	0.097	-9999	-0.37	33	33
AP1	-0.18	0.34	-9999	-0.91	84	84
mol:IP3	-0.015	0.1	-9999	-0.39	33	33
PLCG1	-0.015	0.1	-9999	-0.39	33	33
PDGF/PDGFRA/alphaV Integrin	-0.017	0.12	-9999	-0.4	47	47
RAPGEF1	0.018	0	-9999	-10000	0	0
CRK	0.016	0.033	-9999	-0.52	2	2
mol:Ca2+	-0.015	0.1	-9999	-0.39	33	33
CAV3	0.016	0.029	-9999	-0.34	3	3
CAV1	-0.001	0.083	-9999	-0.33	29	29
SHC/Grb2/SOS1	0.02	0.077	-9999	-0.27	34	34
PDGF/PDGFRA/Shf	-0.009	0.1	-9999	-0.37	35	35
FOS	-0.17	0.34	-9999	-0.89	84	84
JUN	-0.051	0.11	-9999	-0.38	52	52
oligodendrocyte development	-0.017	0.12	-9999	-0.4	47	47
GRB2	0.016	0.024	-9999	-0.25	4	4
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
mol:DAG	-0.015	0.1	-9999	-0.39	33	33
PDGF/PDGFRA	-0.025	0.13	-9999	-0.5	37	37
actin cytoskeleton reorganization	-0.01	0.11	-9999	-0.39	38	38
SRF	0.028	0.025	-9999	-0.35	1	1
SHC1	0.017	0.023	-9999	-0.52	1	1
PI3K	-0.007	0.11	-9999	-0.34	49	49
PDGF/PDGFRA/Crk/C3G	0.01	0.085	-9999	-0.31	33	33
JAK1	-0.009	0.1	-9999	-0.38	37	37
ELK1/SRF	0.012	0.083	-9999	-0.29	34	34
SHB	0.008	0.067	-9999	-0.41	12	12
SHF	0.01	0.049	-9999	-0.27	15	15
CSNK2A1	0.025	0.029	-9999	-0.49	1	1
GO:0007205	-0.018	0.11	-9999	-0.42	33	33
SOS1	0.017	0.023	-9999	-0.52	1	1
Ras protein signal transduction	0.019	0.077	-9999	-0.26	34	34
PDGF/PDGFRA/SHB	-0.01	0.11	-9999	-0.39	38	38
PDGF/PDGFRA/Caveolin-1	-0.016	0.12	-9999	-0.41	36	36
ITGAV	-0.002	0.1	-9999	-0.48	21	21
ELK1	-0.018	0.1	-9999	-0.36	35	35
PIK3CA	0.016	0.029	-9999	-0.34	3	3
PDGF/PDGFRA/Crk	-0.004	0.1	-9999	-0.38	33	33
JAK-STAT cascade	-0.009	0.1	-9999	-0.38	37	37
cell proliferation	-0.009	0.1	-9999	-0.37	35	35

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.023	0.028	-9999	-0.37	1	1
VLDLR	-0.061	0.17	-9999	-0.4	100	100
CRKL	0.014	0.047	-9999	-0.52	4	4
LRPAP1	0.016	0.026	-9999	-0.39	2	2
FYN	0.008	0.067	-9999	-0.41	12	12
ITGA3	-0.003	0.096	-9999	-0.41	25	25
RELN/VLDLR/Fyn	-0.023	0.12	-9999	-0.32	64	64
MAPK8IP1/MKK7/MAP3K11/JNK1	0.038	0.061	-9999	-0.26	18	18
AKT1	-0.011	0.11	-9999	-0.42	15	15
MAP2K7	0.017	0.023	-9999	-0.52	1	1
RAPGEF1	0.018	0	-9999	-10000	0	0
DAB1	0.018	0	-9999	-10000	0	0
RELN/LRP8/DAB1	-0.011	0.094	-9999	-0.28	42	42
LRPAP1/LRP8	-0.027	0.11	-9999	-0.37	37	37
RELN/LRP8/DAB1/Fyn	-0.006	0.096	-9999	-0.26	48	48
DAB1/alpha3/beta1 Integrin	-0.067	0.11	-9999	-0.37	26	26
long-term memory	-0.002	0.1	-9999	-0.24	65	65
DAB1/LIS1	-0.028	0.12	-9999	-0.38	15	15
DAB1/CRLK/C3G	-0.059	0.097	-9999	-0.37	16	16
PIK3CA	0.016	0.029	-9999	-0.34	3	3
DAB1/NCK2	-0.029	0.12	-9999	-0.36	16	16
ARHGEF2	0.004	0.079	-9999	-0.41	17	17
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	0.017	0.012	-9999	-0.25	1	1
CDK5R1	0.014	0.031	-9999	-0.25	7	7
RELN	0.01	0.059	-9999	-0.38	11	11
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
RELN/LRP8/Fyn	-0.02	0.11	-9999	-0.32	48	48
GRIN2A/RELN/LRP8/DAB1/Fyn	0.004	0.097	-9999	-0.26	47	47
MAPK8	0.015	0.04	-9999	-0.52	3	3
RELN/VLDLR/DAB1	-0.014	0.1	-9999	-0.28	59	59
ITGB1	0.014	0.044	-9999	-0.41	5	5
MAP1B	-0.058	0.15	-9999	-0.3	111	111
RELN/LRP8	-0.015	0.1	-9999	-0.31	43	43
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.009	0.11	-9999	-0.26	65	65
PI3K	0.005	0.082	-9999	-0.37	21	21
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.009	0.078	-9999	-0.39	17	17
RAP1A	-0.019	0.12	-9999	-0.36	17	17
PAFAH1B1	0.017	0.023	-9999	-0.52	1	1
MAPK8IP1	0.011	0.048	-9999	-0.3	11	11
CRLK/C3G	0.023	0.034	-9999	-0.37	4	4
GRIN2B	-0.007	0.1	-9999	-0.44	28	28
NCK2	0.015	0.026	-9999	-0.25	5	5
neuron differentiation	0.011	0.079	-9999	-0.25	13	13
neuron adhesion	-0.016	0.12	-9999	-0.33	28	28
LRP8	-0.057	0.16	-9999	-0.34	110	110
GSK3B	-0.004	0.1	-9999	-0.4	14	14
RELN/VLDLR/DAB1/Fyn	-0.009	0.11	-9999	-0.27	64	64
MAP3K11	0.015	0.035	-9999	-0.43	3	3
RELN/VLDLR/DAB1/P13K	-0.016	0.11	-9999	-0.26	74	74
CDK5	0.016	0.026	-9999	-0.39	2	2
MAPT	-0.089	0.2	-9999	-0.48	107	107
neuron migration	-0.013	0.12	-9999	-0.35	27	27
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.011	0.079	-9999	-0.25	13	13
RELN/VLDLR	-0.045	0.14	-9999	-0.28	113	113

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.019	0.061	-9999	-0.27	21	21
RGS9BP	-0.072	0.18	-9999	-0.41	111	111
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
mol:Na +	-0.016	0.089	-9999	-0.33	24	24
mol:ADP	0.011	0.025	-9999	-0.38	2	2
GNAT2	-0.004	0.1	-9999	-0.49	23	23
RGS9-1/Gbeta5/R9AP	-0.056	0.15	-9999	-0.34	96	96
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.089	-9999	-0.33	33	33
GRK7	0.015	0.035	-9999	-0.43	3	3
CNGB3	-0.006	0.086	-9999	-0.3	39	39
Cone Metarhodopsin II/X-Arrestin	0.013	0.008	-9999	-0.17	1	1
mol:Ca2+	-0.009	0.083	-9999	-0.29	27	27
Cone PDE6	-0.043	0.14	-9999	-0.29	105	105
Cone Metarhodopsin II	0.01	0.019	-9999	-0.29	2	2
Na + (4 Units)	-0.005	0.085	-9999	-0.29	27	27
GNAT2/GDP	-0.049	0.14	-9999	-0.29	112	112
GNB5	0.005	0.081	-9999	-0.5	13	13
mol:GMP (4 units)	0.001	0.091	-9999	-0.31	37	37
Cone Transducin	0.02	0.065	-9999	-0.29	21	21
SLC24A2	0.014	0.044	-9999	-0.41	5	5
GNB3/GNGT2	0.025	0.026	-9999	-0.37	2	2
GNB3	0.017	0.012	-9999	-0.25	1	1
GNAT2/GTP	-0.003	0.076	-9999	-0.35	23	23
CNGA3	-0.028	0.12	-9999	-0.31	73	73
ARR3	0.017	0.012	-9999	-0.25	1	1
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.016	0.089	-9999	-0.33	24	24
mol:Pi	-0.056	0.15	-9999	-0.34	96	96
Cone CNG Channel	-0.014	0.11	-9999	-0.3	53	53
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0.014	0.044	-9999	-0.41	5	5
RGS9	-0.033	0.13	-9999	-0.31	81	81
PDE6C	0.008	0.065	-9999	-0.38	13	13
GNGT2	0.016	0.033	-9999	-0.52	2	2
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.001	0.093	-9999	-0.44	21	21

×

IFN-gamma 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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.012	0.1	-10000	0	-0.26	56	56
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.014	0.047	-10000	0	-0.52	4	4
STAT1 (dimer)/Cbp/p300	-0.01	0.15	-10000	0	-0.43	31	31
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.015	0.061	-10000	0	-0.35	10	10
antigen processing and presentation of peptide antigen via MHC class I	-0.055	0.1	-10000	0	-0.29	60	60
CaM/Ca2+	-0.007	0.097	-10000	0	-0.31	17	17
RAP1A	0.012	0.057	-10000	0	-0.52	6	6
STAT1 (dimer)/SHP2	-0.027	0.13	-10000	0	-0.33	48	48
AKT1	-0.012	0.11	-10000	0	-0.36	19	19
MAP2K1	-0.024	0.12	-10000	0	-0.36	32	32
MAP3K11	-0.011	0.098	-10000	0	-0.3	24	24
IFNGR1	0.01	0.034	-10000	0	-0.27	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.03	0.14	-10000	0	-0.38	46	46
Rap1/GTP	-0.03	0.07	-10000	0	-0.35	11	11
CRKL/C3G	0.023	0.034	-10000	0	-0.37	4	4
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.009	0.11	-10000	0	-0.27	52	52
CEBPB	-0.01	0.16	-10000	0	-0.45	32	32
STAT3	0.015	0.04	-10000	0	-0.52	3	3
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.001	0.11	-10000	0	-0.91	2	2
STAT1	-0.029	0.13	-10000	0	-0.33	48	48
CALM1	0.018	0	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.086	0.17	-10000	0	-0.33	161	161
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
STAT1 (dimer)/PIAS1	-0.019	0.12	-10000	0	-0.37	29	29
CEBPB/PTGES2/Cbp/p300	-0.043	0.11	-10000	0	-0.4	29	29
mol:Ca2+	-0.014	0.1	-10000	0	-0.26	56	56
MAPK3	-0.016	0.14	-10000	0	-0.48	14	14
STAT1 (dimer)	-0.07	0.15	-10000	0	-0.43	55	55
MAPK1	-0.017	0.14	-10000	0	-0.49	17	17
JAK2	0.007	0.056	-10000	0	-0.34	12	12
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
JAK1	0.008	0.059	-10000	0	-0.54	6	6
CAMK2D	-0.005	0.1	-10000	0	-0.4	29	29
DAPK1	0	0.14	-10000	0	-0.51	20	20
SMAD7	0.004	0.073	-10000	0	-0.18	22	22
CBL/CRKL/C3G	0.005	0.095	-10000	0	-0.35	11	11
PI3K	-0.022	0.11	-10000	0	-0.36	21	21
IFNG	-0.086	0.17	-10000	0	-0.33	161	161
apoptosis	-0.007	0.12	0.27	2	-0.39	21	23
CAMK2G	0.017	0.017	-10000	0	-0.25	2	2
STAT3 (dimer)	0.015	0.04	-10000	0	-0.52	3	3
CAMK2A	0.017	0.023	-10000	0	-0.52	1	1
CAMK2B	-0.078	0.18	-10000	0	-0.36	133	133
FRAP1	-0.004	0.1	-10000	0	-0.34	17	17
PRKCD	-0.01	0.11	-10000	0	-0.36	18	18
RAP1B	0.013	0.044	-10000	0	-0.32	8	8
negative regulation of cell growth	-0.055	0.1	-10000	0	-0.29	60	60
PTPN2	0.016	0.024	-10000	0	-0.25	4	4
EP300	0.014	0.047	-10000	0	-0.52	4	4
IRF1	-0.007	0.15	-10000	0	-0.47	35	35
STAT1 (dimer)/PIASy	-0.024	0.13	-10000	0	-0.41	25	25
SOCS1	0.01	0.064	-10000	0	-1.4	1	1
mol:GDP	0.003	0.091	-10000	0	-0.33	11	11
CASP1	-0.017	0.12	-10000	0	-0.28	68	68
PTGES2	0.017	0.012	-10000	0	-0.25	1	1
IRF9	0.017	0.085	-10000	0	-0.32	19	19
mol:PI-3-4-5-P3	-0.048	0.089	-10000	0	-0.34	22	22
RAP1/GDP	-0.03	0.071	-10000	0	-0.37	10	10
CBL	-0.01	0.097	-10000	0	-0.28	30	30
MAP3K1	-0.033	0.12	-10000	0	-0.32	54	54
PIAS1	0.017	0.012	-10000	0	-0.25	1	1
PIAS4	0.012	0.05	-10000	0	-0.43	6	6
antigen processing and presentation of peptide antigen via MHC class II	-0.055	0.1	-10000	0	-0.29	60	60
PTPN11	-0.019	0.1	-10000	0	-0.26	56	56
CREBBP	0.016	0.033	-10000	0	-0.52	2	2
RAPGEF1	0.018	0	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.009	0.027	-9999	-0.17	12	12
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.007	0.062	-9999	-0.4	3	3
STXBP1	0.017	0.017	-9999	-0.25	2	2
ACh/CHRNA1	0.008	0.046	-9999	-0.3	9	9
RAB3GAP2/RIMS1/UNC13B	0.019	0.054	-9999	-0.32	4	4
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.003	0.073	-9999	-0.25	41	41
mol:ACh	0.002	0.026	-9999	-0.1	24	24
RAB3GAP2	0.017	0.023	-9999	-0.52	1	1
STX1A/SNAP25/VAMP2	0.018	0.053	-9999	-0.23	5	5
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	0.008	0.046	-9999	-0.29	9	9
UNC13B	0.011	0.049	-9999	-0.3	12	12
CHRNA1	0.01	0.064	-9999	-0.46	9	9
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.1	0.14	-9999	-0.22	265	265
SNAP25	-0.008	0.055	-9999	-0.14	57	57
VAMP2	0.007	0.011	-9999	-0.26	1	1
SYT1	-0.17	0.21	-9999	-0.36	265	265
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.019	0.026	-9999	-0.27	1	1
STX1A/SNAP25 fragment 1/VAMP2	0.018	0.053	-9999	-0.23	5	5

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.01	0.048	-9999	-0.25	17	17
ELF1	-0.012	0.12	-9999	-0.37	43	43
CCNA2	-0.026	0.13	-9999	-0.39	57	57
PIK3CA	0.016	0.029	-9999	-0.34	3	3
JAK3	0.018	0	-9999	-10000	0	0
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
JAK1	0.012	0.057	-9999	-0.52	6	6
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.01	0.14	-9999	-0.38	38	38
SHC1	0.018	0.023	-9999	-0.52	1	1
SP1	0.015	0.07	-9999	-0.36	16	16
IL2RA	-0.035	0.2	-9999	-0.73	37	37
IL2RB	-0.016	0.12	-9999	-0.43	40	40
SOS1	0.017	0.023	-9999	-0.52	1	1
IL2RG	-0.001	0.078	-9999	-0.28	35	35
G1/S transition of mitotic cell cycle	-0.026	0.2	-9999	-0.57	47	47
PTPN11	0.018	0.023	-9999	-0.52	1	1
CCND2	0.009	0.14	-9999	-0.77	16	16
LCK	-0.073	0.18	-9999	-0.4	117	117
GRB2	0.016	0.024	-9999	-0.25	4	4
IL2	0.012	0.051	-9999	-0.33	10	10
CDK6	-0.019	0.1	-9999	-0.29	63	63
CCND3	0.021	0.12	-9999	-0.45	13	13

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.019	0.071	0.24	15	-0.23	28	43
DAPP1	-0.038	0.14	-10000	0	-0.42	43	43
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.051	0.22	-10000	0	-0.54	64	64
mol:DAG	0.001	0.1	0.19	9	-0.23	49	58
HRAS	0.012	0.051	-10000	0	-0.41	7	7
RAP1A	0.012	0.057	-10000	0	-0.52	6	6
ARF5/GDP	-0.016	0.11	-10000	0	-0.31	31	31
PLCG2	-0.017	0.11	-10000	0	-0.32	55	55
PLCG1	0.016	0.026	-10000	0	-0.39	2	2
ARF5	0.015	0.04	-10000	0	-0.52	3	3
mol:GTP	-0.006	0.068	0.22	15	-0.25	25	40
ARF1/GTP	-0.006	0.067	0.22	15	-0.24	25	40
RHOA	0.005	0.08	-10000	0	-0.52	12	12
YES1	0.007	0.07	-10000	0	-0.43	12	12
RAP1A/GTP	0.015	0.069	0.22	15	-0.25	25	40
ADAP1	-0.006	0.065	0.21	15	-0.24	25	40
ARAP3	-0.006	0.067	0.22	15	-0.25	25	40
INPPL1	0.012	0.055	-10000	0	-0.44	7	7
PREX1	-0.089	0.2	-10000	0	-0.44	124	124
ARHGEF6	-0.019	0.13	-10000	0	-0.41	45	45
ARHGEF7	0.016	0.02	-10000	0	-0.25	3	3
ARF1	0.017	0.023	-10000	0	-0.52	1	1
NRAS	0.005	0.076	-10000	0	-0.4	16	16
FYN	0.008	0.067	-10000	0	-0.41	12	12
ARF6	0.016	0.033	-10000	0	-0.52	2	2
FGR	0.017	0.017	-10000	0	-0.25	2	2
mol:Ca2+	0.006	0.054	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.006	0.073	-10000	0	-0.44	13	13
ZAP70	0.005	0.06	-10000	0	-0.26	24	24
mol:IP3	0.004	0.073	-10000	0	-0.18	24	24
LYN	0.014	0.031	-10000	0	-0.25	7	7
ARF1/GDP	-0.015	0.1	-10000	0	-0.32	28	28
RhoA/GDP	0.003	0.099	0.23	6	-0.34	25	31
PDK1/Src/Hsp90	0.031	0.039	-10000	0	-0.3	6	6
BLNK	-0.012	0.12	-10000	0	-0.51	30	30
actin cytoskeleton reorganization	-0.006	0.12	0.23	6	-0.41	23	29
SRC	0.015	0.035	-10000	0	-0.43	3	3
PLEKHA2	0.014	0.043	-10000	0	-0.31	8	8
RAC1	0.018	0	-10000	0	-10000	0	0
PTEN	-0.003	0.096	-10000	0	-0.5	19	19
HSP90AA1	0.013	0.045	-10000	0	-0.39	6	6
ARF6/GTP	0.019	0.069	0.24	14	-0.33	3	17
RhoA/GTP	0.015	0.082	0.22	14	-0.26	32	46
Src family/SYK family/BLNK-LAT	-0.032	0.17	-10000	0	-0.47	47	47
BLK	-0.019	0.1	-10000	0	-0.29	63	63
PDPK1	0.016	0.026	-10000	0	-0.39	2	2
CYTH1	-0.006	0.065	0.21	15	-0.24	25	40
HCK	-0.005	0.11	-10000	0	-0.47	25	25
CYTH3	-0.006	0.065	0.21	15	-0.24	25	40
CYTH2	-0.006	0.065	0.21	15	-0.24	25	40
KRAS	0.009	0.065	-10000	0	-0.44	10	10
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.025	0.052	0.18	12	-0.22	5	17
SGK1	-0.004	0.047	0.18	13	-0.21	6	19
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.025	0.11	-10000	0	-0.29	41	41
SOS1	0.017	0.023	-10000	0	-0.52	1	1
SYK	-0.023	0.14	-10000	0	-0.48	43	43
ARF6/GDP	0.005	0.085	0.24	6	-0.3	20	26
mol:PI-3-4-5-P3	-0.004	0.074	0.25	19	-0.25	25	44
ARAP3/RAP1A/GTP	0.014	0.07	0.22	15	-0.25	25	40
VAV1	-0.014	0.12	-10000	0	-0.39	42	42
mol:PI-3-4-P2	0.008	0.039	-10000	0	-0.32	7	7
RAS family/GTP/PI3K Class I	0.022	0.069	-10000	0	-0.25	25	25
PLEKHA1	0.012	0.052	-10000	0	-0.32	12	12
Rac1/GDP	-0.014	0.1	-10000	0	-0.32	27	27
LAT	0.002	0.068	-10000	0	-0.27	29	29
Rac1/GTP	-0.03	0.14	-10000	0	-0.4	42	42
ITK	-0.008	0.1	0.22	14	-0.25	61	75
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.008	0.13	0.22	8	-0.32	50	58
LCK	-0.074	0.18	-10000	0	-0.4	117	117
BTK	0.007	0.091	0.22	14	-0.27	37	51

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.1	0.22	-10000	0	-0.63	43	43
RAD9A	0.018	0	-10000	0	-10000	0	0
AP1	-0.1	0.19	-10000	0	-0.43	107	107
IFNAR2	0.013	0.036	-10000	0	-0.3	6	6
AKT1	-0.053	0.12	-10000	0	-0.26	75	75
ER alpha/Oestrogen	-0.12	0.18	-10000	0	-0.33	199	199
NFX1/SIN3/HDAC complex	0.038	0.048	-10000	0	-0.31	2	2
EGF	-0.14	0.23	-10000	0	-0.42	193	193
SMG5	0.016	0.029	-10000	0	-0.34	3	3
SMG6	0.017	0.023	-10000	0	-0.52	1	1
SP3/HDAC2	0.019	0.041	-10000	0	-0.37	2	2
TERT/c-Abl	-0.089	0.21	-10000	0	-0.59	42	42
SAP18	0.017	0.001	-10000	0	-10000	0	0
MRN complex	0.03	0.045	-10000	0	-0.3	9	9
WT1	-0.1	0.19	-10000	0	-0.35	172	172
WRN	0.012	0.049	-10000	0	-0.34	9	9
SP1	0.016	0.025	-10000	0	-0.53	1	1
SP3	0.017	0.003	-10000	0	-10000	0	0
TERF2IP	0.018	0	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.099	0.17	-10000	0	-0.55	35	35
Mad/Max	0.021	0.023	-10000	0	-10000	0	0
TERT	-0.1	0.23	-10000	0	-0.66	40	40
CCND1	-0.2	0.44	-10000	0	-1.1	89	89
MAX	0.017	0.004	-10000	0	-10000	0	0
RBBP7	0.01	0.051	-10000	0	-0.3	13	13
RBBP4	0.016	0.026	-10000	0	-0.39	2	2
TERF2	0.014	0.036	-10000	0	-0.46	3	3
PTGES3	0.016	0.026	-10000	0	-0.39	2	2
SIN3A	0.017	0.001	-10000	0	-10000	0	0
Telomerase/911	0.026	0.046	-10000	0	-0.35	2	2
CDKN1B	-0.072	0.19	-10000	0	-0.65	33	33
RAD1	0.016	0.033	-10000	0	-0.52	2	2
XRCC5	0.018	0	-10000	0	-10000	0	0
XRCC6	0.017	0.012	-10000	0	-0.25	1	1
SAP30	0.012	0.053	-10000	0	-0.48	6	6
TRF2/PARP2	0.024	0.03	-10000	0	-0.36	3	3
UBE3A	0.015	0.033	-10000	0	-0.52	2	2
JUN	-0.034	0.15	-10000	0	-0.46	57	57
E6	-0.001	0.003	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.011	0.025	-10000	0	-0.38	2	2
FOS	-0.11	0.2	-10000	0	-0.37	171	171
IFN-gamma/IRF1	-0.075	0.16	-10000	0	-0.36	103	103
PARP2	0.017	0.012	-10000	0	-0.25	1	1
BLM	-0.021	0.13	-10000	0	-0.4	48	48
Telomerase	0.025	0.06	-10000	0	-0.34	3	3
IRF1	-0.017	0.12	-10000	0	-0.37	40	40
ESR1	-0.16	0.24	-10000	0	-0.46	199	199
KU/TER	0.026	0.008	-10000	0	-10000	0	0
ATM/TRF2	0.025	0.023	-10000	0	-0.26	3	3
ubiquitin-dependent protein catabolic process	0.043	0.051	-10000	0	-0.35	2	2
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.043	0.052	-10000	0	-0.36	2	2
HDAC1	0.016	0.023	-10000	0	-0.52	1	1
HDAC2	0.008	0.055	-10000	0	-0.3	15	15
ATM	0.001	0.017	0.21	3	-10000	0	3
SMAD3	0.015	0.059	-10000	0	-0.36	11	11
ABL1	0.018	0	-10000	0	-10000	0	0
MXD1	0.014	0.031	-10000	0	-0.25	7	7
MRE11A	0.018	0	-10000	0	-10000	0	0
HUS1	0.016	0.02	-10000	0	-0.25	3	3
RPS6KB1	0.008	0.049	-10000	0	-0.25	18	18
TERT/NF kappa B1/14-3-3	-0.091	0.22	-10000	0	-0.61	45	45
NR2F2	-0.05	0.17	-10000	0	-0.44	79	79
MAPK3	0.019	0.041	-10000	0	-0.37	4	4
MAPK1	0.018	0.044	-10000	0	-0.37	5	5
TGFB1/TGF beta receptor Type II	0.017	0.023	-10000	0	-0.52	1	1
NFKB1	0.017	0.023	-10000	0	-0.52	1	1
HNRNPC	0.018	0	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.001	0.017	0.21	3	-10000	0	3
NBN	0.015	0.035	-10000	0	-0.43	3	3
EGFR	-0.079	0.18	-10000	0	-0.35	139	139
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.15	0.2	-10000	0	-0.42	173	173
MYC	-0.027	0.14	-10000	0	-0.43	52	52
IL2	0.01	0.052	-10000	0	-0.34	10	10
KU	0.026	0.008	-10000	0	-10000	0	0
RAD50	0.011	0.062	-10000	0	-0.52	7	7
HSP90AA1	0.013	0.045	-10000	0	-0.39	6	6
TGFB1	0.017	0.024	-10000	0	-0.52	1	1
TRF2/BLM	-0.002	0.091	-10000	0	-0.35	30	30
FRAP1	0.018	0	-10000	0	-10000	0	0
KU/TERT	-0.08	0.21	-10000	0	-0.6	37	37
SP1/HDAC2	0.019	0.048	-10000	0	-0.42	3	3
PINX1	0.016	0.02	-10000	0	-0.25	3	3
Telomerase/EST1A	-0.1	0.17	-10000	0	-0.55	36	36
Smad3/Myc	-0.003	0.099	-10000	0	-0.31	46	46
911 complex	0.034	0.024	-10000	0	-0.3	2	2
IFNG	-0.092	0.18	-10000	0	-0.33	161	161
Telomerase/PinX1	-0.099	0.17	-10000	0	-0.56	35	35
Telomerase/AKT1/mTOR/p70S6K	-0.008	0.092	-10000	0	-0.42	7	7
SIN3B	0.017	0.012	-10000	0	-0.25	1	1
YWHAE	0.016	0.029	-10000	0	-0.34	3	3
Telomerase/EST1B	-0.1	0.17	-10000	0	-0.55	36	36
response to DNA damage stimulus	0.004	0.005	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.044	0.047	-10000	0	-0.27	11	11
TRF2/WRN	0.02	0.043	-10000	0	-0.35	6	6
Telomerase/hnRNP C1/C2	-0.099	0.17	-10000	0	-0.56	33	33
E2F1	0.005	0.071	-10000	0	-0.37	16	16
ZNFX1	0.007	0.071	-10000	0	-0.42	13	13
PIF1	0.015	0.026	-10000	0	-0.25	5	5
NCL	0.018	0	-10000	0	-10000	0	0
DKC1	0.016	0.02	-10000	0	-0.25	3	3
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Insulin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.048	0.1	-9999	-0.26	88	88
TC10/GTP	-0.022	0.063	-9999	-0.23	39	39
Insulin Receptor/Insulin/IRS1/Shp2	0.005	0.11	-9999	-0.29	63	63
HRAS	0.012	0.051	-9999	-0.41	7	7
APS homodimer	0	0	-9999	-10000	0	0
GRB14	-0.16	0.21	-9999	-0.36	247	247
FOXO3	-0.021	0.065	-9999	-0.71	4	4
AKT1	-0.068	0.14	-9999	-0.37	44	44
INSR	0.015	0.038	-9999	-0.38	4	4
Insulin Receptor/Insulin	0.036	0.079	-9999	-0.49	4	4
mol:GTP	0	0	-9999	-10000	0	0
GRB10	-0.003	0.097	-9999	-0.43	24	24
SORBS1	-0.032	0.14	-9999	-0.39	65	65
CRK	0.016	0.033	-9999	-0.52	2	2
PTPN1	0.023	0.075	-9999	-0.48	4	4
CAV1	-0.012	0.11	-9999	-0.27	69	69
CBL/APS/CAP/Crk-II/C3G	0.014	0.078	-9999	-0.25	35	35
Insulin Receptor/Insulin/IRS1/NCK2	0.004	0.11	-9999	-0.29	62	62
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.011	0.11	-9999	-0.25	80	80
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.013	0.09	-9999	-0.46	6	6
RPS6KB1	-0.06	0.13	-9999	-0.33	50	50
PARD6A	0.004	0.081	-9999	-0.44	16	16
CBL	0.017	0.012	-9999	-0.25	1	1
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	-0.014	0.11	-9999	-0.78	11	11
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.082	0.11	-9999	-0.33	51	51
HRAS/GTP	-0.028	0.073	-9999	-0.33	7	7
Insulin Receptor	0.015	0.037	-9999	-0.38	4	4
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.014	0.1	-9999	-0.26	62	62
PRKCI	-0.033	0.1	-9999	-0.52	21	21
Insulin Receptor/Insulin/GRB14/PDK1	-0.098	0.12	-9999	-0.36	50	50
SHC1	0.017	0.023	-9999	-0.52	1	1
negative regulation of MAPKKK cascade	0.009	0.12	-9999	-0.7	11	11
PI3K	-0.005	0.11	-9999	-0.26	80	80
NCK2	0.015	0.026	-9999	-0.25	5	5
RHOQ	0.012	0.053	-9999	-0.48	6	6
mol:H2O2	-0.002	0.008	-9999	-10000	0	0
HRAS/GDP	0.009	0.036	-9999	-0.29	7	7
AKT2	-0.065	0.13	-9999	-0.36	42	42
PRKCZ	-0.028	0.074	-9999	-0.53	9	9
SH2B2	0	0	-9999	-10000	0	0
SHC/SHIP	-0.002	0.093	-9999	-0.25	63	63
F2RL2	-0.074	0.19	-9999	-0.44	105	105
TRIP10	0.013	0.048	-9999	-0.47	5	5
Insulin Receptor/Insulin/Shc	0.032	0.029	-9999	-0.27	4	4
TC10/GTP/CIP4/Exocyst	0.018	0.045	-9999	-0.31	9	9
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.05	0.036	-9999	-0.3	4	4
RAPGEF1	0.018	0	-9999	-10000	0	0
RASA1	0.004	0.078	-9999	-0.42	16	16
NCK1	0.011	0.045	-9999	-0.28	12	12
CBL/APS/CAP/Crk-II	0.005	0.082	-9999	-0.28	35	35
TC10/GDP	0.009	0.039	-9999	-0.34	6	6
Insulin Receptor/Insulin/SHC/GRB10	0.032	0.064	-9999	-0.27	20	20
INPP5D	-0.014	0.096	-9999	-0.27	62	62
SOS1	0.017	0.023	-9999	-0.52	1	1
SGK1	-0.01	0.012	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.017	0.023	-9999	-0.52	1	1
IRS1	-0.048	0.17	-9999	-0.49	68	68
p62DOK/RasGAP	0.009	0.12	-9999	-0.71	11	11
INS	0.017	0.025	-9999	-0.52	1	1
mol:PI-3-4-P2	-0.013	0.096	-9999	-0.27	62	62
GRB2	0.016	0.024	-9999	-0.25	4	4
EIF4EBP1	-0.067	0.13	-9999	-0.34	57	57
PTPRA	0.017	0.028	-9999	-0.4	2	2
PIK3CA	0.016	0.029	-9999	-0.34	3	3
TC10/GTP/CIP4	0.018	0.045	-9999	-0.31	9	9
PDPK1	0.016	0.026	-9999	-0.39	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.009	0.095	-9999	-0.4	6	6
Insulin Receptor/Insulin/IRS1	-0.006	0.11	-9999	-0.29	62	62
Insulin Receptor/Insulin/IRS3	0.024	0.034	-9999	-0.37	3	3
Par3/Par6	-0.02	0.13	-9999	-0.29	86	86

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.01	0.079	-9999	-0.26	32	32
STMN1	0.002	0.088	-9999	-0.38	22	22
Aurora B/RasGAP/Survivin	-0.011	0.12	-9999	-0.34	53	53
Chromosomal passenger complex/Cul3 protein complex	-0.052	0.14	-9999	-0.32	67	67
BIRC5	-0.038	0.16	-9999	-0.43	67	67
DES	-0.026	0.13	-9999	-0.68	16	16
Aurora C/Aurora B/INCENP	0.015	0.062	-9999	-0.29	14	14
Aurora B/TACC1	-0.005	0.088	-9999	-0.32	32	32
Aurora B/PP2A	0.019	0.042	-9999	-0.39	3	3
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.011	0.033	-9999	-0.21	9	9
mitotic metaphase/anaphase transition	0	0.005	-9999	-10000	0	0
NDC80	-0.014	0.12	-9999	-0.4	39	39
Cul3 protein complex	-0.048	0.14	-9999	-0.33	93	93
KIF2C	-0.061	0.24	-9999	-0.65	59	59
PEBP1	0.013	0.047	-9999	-0.53	4	4
KIF20A	-0.027	0.14	-9999	-0.46	49	49
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.011	0.07	-9999	-0.38	13	13
SEPT1	0.008	0.052	-9999	-0.27	17	17
SMC2	0.003	0.077	-9999	-0.36	20	20
SMC4	0.014	0.04	-9999	-0.34	6	6
NSUN2/NPM1/Nucleolin	0.015	0.082	-9999	-0.87	3	3
PSMA3	0.017	0.012	-9999	-0.25	1	1
G2/M transition of mitotic cell cycle	0	0.003	-9999	-10000	0	0
H3F3B	0.013	0.04	-9999	-0.33	5	5
AURKB	0.009	0.058	-9999	-0.32	14	14
AURKC	0.008	0.053	-9999	-0.27	18	18
CDCA8	-0.016	0.12	-9999	-0.4	42	42
cytokinesis	-0.049	0.26	-9999	-0.72	51	51
Aurora B/Septin1	-0.036	0.23	-9999	-0.65	51	51
AURKA	-0.012	0.11	-9999	-0.41	36	36
INCENP	0.001	0.082	-9999	-0.37	22	22
KLHL13	-0.095	0.2	-9999	-0.39	146	146
BUB1	-0.052	0.17	-9999	-0.44	81	81
hSgo1/Aurora B/Survivin	-0.016	0.14	-9999	-0.38	52	52
EVI5	0.013	0.047	-9999	-0.52	4	4
RhoA/GTP	-0.045	0.24	-9999	-0.6	65	65
SGOL1	-0.01	0.11	-9999	-0.38	37	37
CENPA	-0.041	0.21	-9999	-0.59	51	51
NCAPG	0	0	-9999	-10000	0	0
Aurora B/HC8 Proteasome	0.02	0.041	-9999	-0.39	3	3
NCAPD2	0.012	0.04	-9999	-0.25	12	12
Aurora B/PP1-gamma	0.018	0.05	-9999	-0.38	6	6
RHOA	0.005	0.08	-9999	-0.52	12	12
NCAPH	-0.008	0.11	-9999	-0.46	29	29
NPM1	0.012	0.052	-9999	-0.6	3	3
RASA1	0.004	0.078	-9999	-0.42	16	16
KLHL9	-0.001	0.096	-9999	-0.49	19	19
mitotic prometaphase	-0.001	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.041	-9999	-0.38	3	3
PPP1CC	0.015	0.04	-9999	-0.52	3	3
Centraspindlin	-0.053	0.27	-9999	-0.69	60	60
RhoA/GDP	0.004	0.058	-9999	-0.38	12	12
NSUN2	0.012	0.054	-9999	-0.5	4	4
MYLK	0.003	0.07	-9999	-0.33	20	20
KIF23	-0.024	0.14	-9999	-0.45	47	47
VIM	-0.01	0.11	-9999	-0.38	34	34
RACGAP1	-0.004	0.1	-9999	-0.5	22	22
mitosis	0	0	-9999	-10000	0	0
NCL	0.013	0.052	-9999	-0.6	3	3
Chromosomal passenger complex	-0.045	0.22	-9999	-0.56	58	58
Chromosomal passenger complex/EVI5	-0.012	0.15	-9999	-0.35	66	66
TACC1	-0.022	0.13	-9999	-0.41	49	49
PPP2R5D	0.016	0.02	-9999	-0.25	3	3
CUL3	0.01	0.06	-9999	-0.43	9	9
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

p75(NTR)-mediated signaling

Figure S73. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S73. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.019	0.05	-10000	0	-0.37	8	8
Necdin/E2F1	-0.027	0.14	-10000	0	-0.38	62	62
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.01	0.11	-10000	0	-0.27	78	78
NGF (dimer)/p75(NTR)/BEX1	-0.016	0.075	-10000	0	-0.29	12	12
NT-4/5 (dimer)/p75(NTR)	0.004	0.045	-10000	0	-0.2	23	23
IKBKB	0.012	0.047	-10000	0	-0.31	10	10
AKT1	0.01	0.072	-10000	0	-0.25	30	30
IKBKG	0.018	0	-10000	0	-10000	0	0
BDNF	-0.016	0.091	-10000	0	-0.26	64	64
MGDIs/NGR/p75(NTR)/LINGO1	-0.003	0.086	-10000	0	-0.31	22	22
FURIN	0.004	0.076	-10000	0	-0.37	19	19
proBDNF (dimer)/p75(NTR)/Sortilin	0.004	0.075	-10000	0	-0.33	11	11
LINGO1	-0.019	0.095	-10000	0	-0.26	69	69
Sortilin/TRAF6/NRIF	-0.017	0.056	-10000	0	-0.33	5	5
proBDNF (dimer)	-0.016	0.09	-10000	0	-0.26	64	64
NTRK1	0.01	0.053	-10000	0	-0.32	12	12
RTN4R	0.001	0.087	-10000	0	-0.41	21	21
neuron apoptosis	0.003	0.1	-10000	0	-0.47	7	7
IRAK1	0.015	0.029	-10000	0	-0.25	6	6
SHC1	0.013	0.04	-10000	0	-0.31	4	4
ARHGDIA	0.016	0.029	-10000	0	-0.34	3	3
RhoA/GTP	0.004	0.058	-10000	0	-0.38	12	12
Gamma Secretase	0.033	0.069	-10000	0	-0.25	25	25
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.001	0.095	-10000	0	-0.3	43	43
MAGEH1	-0.019	0.14	-10000	0	-0.52	36	36
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.013	0.11	-10000	0	-0.3	65	65
Mammalian IAPs/DIABLO	-0.024	0.11	-10000	0	-0.28	76	76
proNGF (dimer)	0	0	-10000	0	-10000	0	0
MAGED1	-0.008	0.11	-10000	0	-0.48	27	27
APP	-0.029	0.14	-10000	0	-0.43	56	56
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
ZNF274	0.013	0.044	-10000	0	-0.32	8	8
RhoA/GDP/RHOGDI	0.017	0.057	-10000	0	-0.27	16	16
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	0.006	0.054	0.15	3	-0.26	10	13
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.026	0.04	-10000	0	-0.23	9	9
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.016	0.041	-10000	0	-0.31	4	4
NCSTN	0.017	0.023	-10000	0	-0.52	1	1
mol:GTP	-0.016	0.089	-10000	0	-0.31	31	31
PSENEN	0.017	0.012	-10000	0	-0.25	1	1
mol:ceramide	0.014	0.056	-10000	0	-0.29	12	12
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.022	0.049	-10000	0	-0.26	1	1
p75(NTR)/beta APP	-0.017	0.11	-10000	0	-0.37	39	39
BEX1	-0.039	0.11	-10000	0	-0.26	108	108
mol:GDP	0.002	0.037	-10000	0	-0.32	3	3
NGF (dimer)	-0.038	0.13	-10000	0	-0.29	101	101
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.009	0.081	-10000	0	-0.28	23	23
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
RAC1/GTP	0.015	0.032	-10000	0	-0.27	3	3
MYD88	0.013	0.048	-10000	0	-0.47	5	5
CHUK	0.005	0.081	-10000	0	-0.5	13	13
NGF (dimer)/p75(NTR)/PKA	-0.016	0.09	-10000	0	-0.31	31	31
RHOB	-0.041	0.17	-10000	0	-0.52	58	58
RHOA	0.005	0.08	-10000	0	-0.52	12	12
MAGE-G1/E2F1	0.018	0.051	-10000	0	-0.37	7	7
NT3 (dimer)	-0.021	0.11	-10000	0	-0.28	68	68
TP53	-0.001	0.098	-10000	0	-0.37	12	12
PRDM4	0.017	0.049	-10000	0	-0.28	10	10
BDNF (dimer)	-0.12	0.2	-10000	0	-0.37	173	173
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
SORT1	0.009	0.065	-10000	0	-0.44	10	10
activation of caspase activity	-0.013	0.11	-10000	0	-0.27	78	78
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.022	0.052	-10000	0	-0.28	11	11
RHOC	0.015	0.04	-10000	0	-0.52	3	3
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	0	0.095	-10000	0	-0.3	16	16
DIABLO	0.018	0	-10000	0	-10000	0	0
SMPD2	0.014	0.056	-10000	0	-0.3	12	12
APH1B	0.001	0.093	-10000	0	-0.51	17	17
APH1A	0.003	0.067	-10000	0	-0.29	25	25
proNGF (dimer)/p75(NTR)/Sortilin	0.011	0.055	-10000	0	-0.31	10	10
PSEN1	0.013	0.052	-10000	0	-0.52	5	5
APAF-1/Pro-Caspase 9	0.022	0.041	-10000	0	-0.37	5	5
NT3 (dimer)/p75(NTR)	-0.009	0.09	-10000	0	-0.4	13	13
MAPK8	0.014	0.08	-10000	0	-0.3	6	6
MAPK9	0.005	0.096	-10000	0	-0.37	10	10
APAF1	0.012	0.051	-10000	0	-0.41	7	7
NTF3	-0.021	0.11	-10000	0	-0.28	68	68
NTF4	0	0	-10000	0	-10000	0	0
NDN	-0.044	0.17	-10000	0	-0.49	65	65
RAC1/GDP	0.013	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.028	0.12	-10000	0	-0.25	96	96
p75 CTF/Sortilin/TRAF6/NRIF	0.036	0.048	-10000	0	-0.27	10	10
RhoA-B-C/GTP	-0.016	0.089	-10000	0	-0.31	31	31
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.021	0.07	-10000	0	-0.26	14	14
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.015	0.071	-10000	0	-0.29	12	12
PRKACB	-0.036	0.14	-10000	0	-0.34	79	79
proBDNF (dimer)/p75 ECD	0.002	0.064	-10000	0	-0.34	2	2
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.085	0.19	-10000	0	-0.41	128	128
BIRC2	0.016	0.02	-10000	0	-0.25	3	3
neuron projection morphogenesis	-0.033	0.11	0.2	2	-0.35	36	38
BAD	0.008	0.091	-10000	0	-0.31	11	11
RIPK2	0.013	0.04	-10000	0	-0.28	9	9
NGFR	0.004	0.065	-10000	0	-0.29	23	23
CYCS	0.01	0.074	-10000	0	-0.25	34	34
ADAM17	0.016	0.024	-10000	0	-0.25	4	4
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.024	0.044	-10000	0	-0.27	6	6
BCL2L11	0.008	0.091	-10000	0	-0.31	11	11
BDNF (dimer)/p75(NTR)	-0.006	0.075	-10000	0	-0.4	4	4
PI3K	0.011	0.072	-10000	0	-0.28	25	25
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.022	0.05	-10000	0	-0.28	10	10
NDNL2	0.018	0	-10000	0	-10000	0	0
YWHAE	0.016	0.029	-10000	0	-0.34	3	3
PRKCI	0.002	0.085	-10000	0	-0.43	18	18
NGF (dimer)/p75(NTR)	0.004	0.045	-10000	0	-0.2	23	23
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.008	0.08	-10000	0	-0.28	33	33
TRAF6	0.017	0.023	-10000	0	-0.52	1	1
RAC1	0.018	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
PLG	0.016	0.033	-10000	0	-0.52	2	2
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	0.005	0.07	-10000	0	-0.29	17	17
SQSTM1	0.012	0.053	-10000	0	-0.48	6	6
NGFRAP1	-0.055	0.18	-10000	0	-0.52	72	72
CASP3	0.01	0.087	-10000	0	-0.29	11	11
E2F1	0.006	0.07	-10000	0	-0.37	16	16
CASP9	0.017	0.023	-10000	0	-0.52	1	1
IKK complex	-0.013	0.047	-10000	0	-0.34	3	3
NGF (dimer)/TRKA	0.008	0.037	-10000	0	-0.22	12	12
MMP7	-0.095	0.21	-10000	0	-0.44	129	129
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.028	0.054	-10000	0	-0.25	13	13
MMP3	-0.13	0.22	-10000	0	-0.42	177	177
APAF-1/Caspase 9	-0.046	0.077	-10000	0	-0.31	10	10

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	0.019	0.27	-9999	-0.76	29	29
PCK1	0.019	0.2	-9999	-0.88	7	7
HNF4A	0.033	0.27	-9999	-0.76	23	23
KCNJ11	-0.015	0.38	-9999	-1	49	49
AKT1	0.011	0.17	-9999	-0.43	30	30
response to starvation	0.006	0.003	-9999	-10000	0	0
DLK1	0.019	0.3	-9999	-0.77	30	30
NKX2-1	0.074	0.14	-9999	-10000	0	0
ACADM	0.01	0.29	-9999	-0.77	36	36
TAT	0.018	0.17	-9999	-0.6	3	3
CEBPB	0.01	0.071	-9999	-0.33	20	20
CEBPA	0.011	0.085	-9999	-0.5	14	14
TTR	-0.041	0.28	-9999	-0.68	55	55
PKLR	0.022	0.26	-9999	-0.72	28	28
APOA1	0.032	0.3	-9999	-0.83	25	25
CPT1C	0	0.3	-9999	-0.83	37	37
ALAS1	0.039	0.19	-9999	-1.6	2	2
TFRC	-0.047	0.39	-9999	-1.1	47	47
FOXF1	-0.002	0.062	-9999	-0.3	19	19
NF1	0.023	0.039	-9999	-0.46	3	3
HNF1A (dimer)	0.03	0.047	-9999	-0.24	6	6
CPT1A	0.007	0.3	-9999	-0.84	33	33
HMGCS1	0.018	0.27	-9999	-0.72	30	30
NR3C1	0.007	0.1	-9999	-0.5	19	19
CPT1B	0.022	0.26	-9999	-0.73	27	27
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.02	0.04	-9999	-0.26	7	7
GCK	0.017	0.27	-9999	-0.72	32	32
CREB1	0.02	0.036	-9999	-0.36	2	2
IGFBP1	0.028	0.16	-9999	-0.73	4	4
PDX1	0.035	0.26	-9999	-1.1	14	14
UCP2	-0.025	0.35	-9999	-0.88	54	54
ALDOB	0.024	0.29	-9999	-0.77	29	29
AFP	-0.049	0.15	-9999	-0.66	6	6
BDH1	0.011	0.28	-9999	-0.74	36	36
HADH	0.021	0.3	-9999	-0.81	29	29
F2	0.032	0.3	-9999	-0.84	23	23
HNF1A	0.03	0.047	-9999	-0.24	6	6
G6PC	0.035	0.096	-9999	-1.3	1	1
SLC2A2	0.042	0.22	-9999	-1	6	6
INS	0.002	0.028	-9999	-0.53	1	1
FOXA1	-0.081	0.21	-9999	-0.49	108	108
FOXA3	-0.016	0.13	-9999	-0.38	31	31
FOXA2	0.032	0.35	-9999	-0.82	37	37
ABCC8	-0.2	0.52	-9999	-0.91	168	168
ALB	-0.055	0.17	-9999	-0.76	12	12

×

Ceramide 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
SPHK2	0.01	0.074	-10000	0	-0.37	18	18
MAP4K4	-0.003	0.11	-10000	0	-0.45	12	12
BAG4	0.002	0.07	-10000	0	-0.28	28	28
PKC zeta/ceramide	-0.025	0.04	0.13	8	-0.12	1	9
NFKBIA	0.014	0.042	-10000	0	-0.45	4	4
BIRC3	-0.085	0.19	-10000	0	-0.41	128	128
BAX	-0.003	0.022	-10000	0	-10000	0	0
RIPK1	0.017	0.023	-10000	0	-0.52	1	1
AKT1	0.017	0.051	-10000	0	-0.34	9	9
BAD	-0.018	0.041	0.15	8	-0.18	1	9
SMPD1	0.008	0.06	-10000	0	-0.24	19	19
RB1	-0.028	0.07	0.15	8	-0.32	20	28
FADD/Caspase 8	0.007	0.1	-10000	0	-0.43	11	11
MAP2K4	-0.043	0.092	0.15	1	-0.28	55	56
NSMAF	0.009	0.065	-10000	0	-0.44	10	10
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.01	0.04	0.15	8	-0.18	1	9
EGF	-0.14	0.23	-10000	0	-0.42	193	193
mol:ceramide	-0.027	0.044	0.15	8	-0.12	1	9
MADD	0.018	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.028	0.13	-10000	0	-0.38	56	56
ASAH1	-0.036	0.15	-10000	0	-0.42	65	65
negative regulation of cell cycle	-0.027	0.069	0.15	8	-0.31	20	28
cell proliferation	-0.036	0.097	-10000	0	-0.23	83	83
BID	-0.013	0.12	-10000	0	-0.55	17	17
MAP3K1	-0.041	0.084	0.15	7	-0.3	38	45
EIF2A	-0.013	0.059	-10000	0	-0.26	15	15
TRADD	0.016	0.026	-10000	0	-0.39	2	2
CRADD	0.01	0.063	-10000	0	-0.49	8	8
MAPK3	0.002	0.039	-10000	0	-0.19	1	1
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.001	0.04	0.16	1	-0.19	1	2
Cathepsin D/ceramide	-0.022	0.055	0.14	7	-0.23	11	18
FADD	-0.006	0.11	-10000	0	-0.38	19	19
KSR1	-0.017	0.042	0.15	8	-0.2	1	9
MAPK8	-0.03	0.069	0.14	5	-0.2	51	56
PRKRA	-0.017	0.042	0.15	8	-10000	0	8
PDGFA	-0.003	0.099	-10000	0	-0.44	24	24
TRAF2	0.014	0.042	-10000	0	-0.45	4	4
IGF1	-0.1	0.2	-10000	0	-0.41	146	146
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.026	0.044	0.15	8	-0.12	1	9
CTSD	0.002	0.075	-10000	0	-0.32	24	24
regulation of nitric oxide biosynthetic process	0.026	0.017	-10000	0	-0.37	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.035	0.11	-10000	0	-0.25	81	81
PRKCD	0.014	0.042	-10000	0	-0.45	4	4
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.028	0.13	-10000	0	-0.38	56	56
RelA/NF kappa B1	0.026	0.017	-10000	0	-0.37	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0	0.091	-10000	0	-0.44	20	20
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.005	0.11	-10000	0	-0.45	13	13
TNFR1A/BAG4/TNF-alpha	0.012	0.074	-10000	0	-0.31	18	18
mol:Sphingosine-1-phosphate	0.01	0.074	-10000	0	-0.37	18	18
MAP2K1	-0.002	0.039	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.018	0	-10000	0	-10000	0	0
CYCS	0.027	0.065	0.16	76	-10000	0	76
TNFRSF1A	0.016	0.033	-10000	0	-0.52	2	2
NFKB1	0.017	0.023	-10000	0	-0.52	1	1
TNFR1A/BAG4	0.014	0.054	-10000	0	-0.37	5	5
EIF2AK2	-0.02	0.061	0.15	4	-0.26	18	22
TNF-alpha/TNFR1A/FAN	0.016	0.073	-10000	0	-0.31	21	21
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.02	0.062	-10000	0	-0.31	1	1
MAP2K2	-0.003	0.043	-10000	0	-0.24	4	4
SMPD3	0.005	0.072	-10000	0	-0.3	14	14
TNF	-0.004	0.094	-10000	0	-0.36	31	31
PKC zeta/PAR4	0.001	0.065	-10000	0	-0.32	20	20
mol:PHOSPHOCHOLINE	0.055	0.1	0.22	129	-10000	0	129
NF kappa B1/RelA/I kappa B alpha	0.03	0.055	-10000	0	-0.25	18	18
AIFM1	0.027	0.065	0.16	75	-10000	0	75
BCL2	-0.11	0.22	-10000	0	-0.47	144	144

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.017	0.13	-10000	0	-0.48	37	37
HRAS	0.012	0.051	-10000	0	-0.41	7	7
EGFR	-0.079	0.18	-10000	0	-0.35	139	139
AKT	0.014	0.079	-10000	0	-0.32	16	16
FOXO3	0.011	0.053	-10000	0	-0.37	9	9
AKT1	0.011	0.053	-10000	0	-0.37	9	9
FOXO1	0	0.092	-10000	0	-0.46	19	19
AKT3	-0.006	0.084	-10000	0	-0.28	43	43
FOXO4	0.017	0.023	-10000	0	-0.52	1	1
MET	0	0.075	-10000	0	-0.29	31	31
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
PIK3CB	0.012	0.055	-10000	0	-0.44	7	7
NRAS	0.005	0.076	-10000	0	-0.4	16	16
PIK3CG	-0.007	0.1	-10000	0	-0.41	31	31
PIK3R3	0	0.091	-10000	0	-0.43	21	21
PIK3R2	0.018	0	-10000	0	-10000	0	0
NF1	0.015	0.035	-10000	0	-0.43	3	3
RAS	-0.027	0.097	0.21	1	-0.27	47	48
ERBB2	-0.027	0.12	-10000	0	-0.31	72	72
proliferation/survival/translation	-0.028	0.057	0.23	10	-0.17	3	13
PI3K	-0.019	0.099	0.18	6	-0.23	65	71
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
KRAS	0.009	0.065	-10000	0	-0.44	10	10
FOXO	0.039	0.038	0.18	3	-0.18	2	5
AKT2	0.017	0.012	-10000	0	-0.25	1	1
PTEN	-0.002	0.1	-10000	0	-0.52	19	19

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.001	0.05	0.26	17	-10000	0	17
BUB1B	-0.017	0.12	-10000	0	-0.41	40	40
PLK1	0.002	0.041	-10000	0	-0.12	46	46
PLK1S1	0.002	0.019	-10000	0	-0.053	45	45
KIF2A	0.005	0.054	-10000	0	-0.19	23	23
regulation of mitotic centrosome separation	0.002	0.041	-10000	0	-0.12	46	46
GOLGA2	0.016	0.026	-10000	0	-0.39	2	2
Hec1/SPC24	-0.012	0.094	-10000	0	-0.32	37	37
WEE1	-0.003	0.093	-10000	0	-0.35	25	25
cytokinesis	-0.025	0.16	-10000	0	-0.52	44	44
PP2A-alpha B56	-0.059	0.27	-10000	0	-0.76	62	62
AURKA	-0.002	0.064	-10000	0	-0.29	22	22
PICH/PLK1	-0.023	0.18	-10000	0	-0.48	53	53
CENPE	-0.011	0.096	-10000	0	-0.32	40	40
RhoA/GTP	0.004	0.058	-10000	0	-0.38	12	12
positive regulation of microtubule depolymerization	0.005	0.054	-10000	0	-0.19	23	23
PPP2CA	0.011	0.062	-10000	0	-0.52	7	7
FZR1	0.018	0	-10000	0	-10000	0	0
TPX2	-0.013	0.083	-10000	0	-0.29	40	40
PAK1	-0.023	0.13	-10000	0	-0.38	54	54
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	0.015	0.035	-10000	0	-0.43	3	3
CLSPN	0.002	0.057	-10000	0	-0.38	10	10
GORASP1	0.017	0.023	-10000	0	-0.52	1	1
metaphase	0	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.002	0.019	-10000	0	-0.053	45	45
G2 phase of mitotic cell cycle	-0.001	0.003	0.016	1	-0.013	21	22
STAG2	0.017	0.023	-10000	0	-0.52	1	1
GRASP65/GM130/RAB1/GTP	0.021	0.04	-10000	0	-0.74	1	1
spindle elongation	0.002	0.041	-10000	0	-0.12	46	46
ODF2	0.016	0.024	-10000	0	-0.53	1	1
BUB1	-0.1	0.28	-10000	0	-0.85	60	60
TPT1	0.009	0.019	-10000	0	-10000	0	0
CDC25C	-0.016	0.11	-10000	0	-0.43	35	35
CDC25B	0.004	0.069	-10000	0	-0.3	23	23
SGOL1	-0.001	0.051	-10000	0	-0.26	17	17
RHOA	0.005	0.08	-10000	0	-0.52	12	12
CCNB1/CDK1	-0.013	0.15	-10000	0	-0.48	42	42
CDC14B	0.01	0.03	-10000	0	-0.38	3	3
CDC20	-0.02	0.12	-10000	0	-0.37	51	51
PLK1/PBIP1	-0.011	0.083	-10000	0	-0.24	49	49
mitosis	0.002	0.007	0.035	21	-10000	0	21
FBXO5	0.003	0.054	-10000	0	-0.19	20	20
CDC2	-0.012	0.12	-10000	0	-0.45	34	34
NDC80	-0.029	0.14	-10000	0	-0.41	57	57
metaphase plate congression	0.009	0.023	-10000	0	-10000	0	0
ERCC6L	-0.026	0.19	-10000	0	-0.57	46	46
NLP/gamma Tubulin	0.005	0.022	-10000	0	-0.075	5	5
microtubule cytoskeleton organization	0.009	0.019	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.002	0.01	22	-10000	0	22
PPP1R12A	0.015	0.031	-10000	0	-0.32	4	4
interphase	0	0.002	0.01	22	-10000	0	22
PLK1/PRC1-2	-0.017	0.14	-10000	0	-0.42	48	48
GRASP65/GM130/RAB1/GTP/PLK1	0.028	0.039	-10000	0	-0.22	3	3
RAB1A	0.017	0.023	-10000	0	-0.52	1	1
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.006	0.039	-10000	0	-0.14	22	22
mitotic prometaphase	0	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.058	-10000	0	-0.29	8	8
microtubule-based process	-0.011	0.1	-10000	0	-0.34	41	41
Golgi organization	0.002	0.041	-10000	0	-0.12	46	46
Cohesin/SA2	0.009	0.036	-10000	0	-0.17	4	4
PPP1CB/MYPT1	0.023	0.026	-10000	0	-0.37	1	1
KIF20A	-0.027	0.14	-10000	0	-0.46	49	49
APC/C/CDC20	-0.007	0.089	-10000	0	-0.31	32	32
PPP2R1A	0.017	0.012	-10000	0	-0.25	1	1
chromosome segregation	-0.011	0.082	-10000	0	-0.24	49	49
PRC1	-0.019	0.13	-10000	0	-0.43	43	43
ECT2	-0.001	0.07	-10000	0	-0.24	29	29
C13orf34	0.006	0.037	-10000	0	-0.13	21	21
NUDC	0.009	0.023	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.016	0.12	-10000	0	-0.4	40	40
spindle assembly	0.005	0.031	-10000	0	-0.086	41	41
spindle stabilization	0.002	0.019	-10000	0	-0.052	45	45
APC/C/HCDH1	0.02	0.025	-10000	0	-0.32	3	3
MKLP2/PLK1	-0.011	0.1	-10000	0	-0.34	41	41
CCNB1	-0.016	0.13	-10000	0	-0.5	35	35
PPP1CB	0.016	0.02	-10000	0	-0.25	3	3
BTRC	0.008	0.054	-10000	0	-0.29	16	16
ROCK2	0.008	0.055	-10000	0	-0.24	16	16
TUBG1	0.008	0.02	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.046	0.14	-10000	0	-0.48	40	40
MLF1IP	-0.018	0.1	-10000	0	-0.32	49	49
INCENP	0.001	0.081	-10000	0	-0.37	22	22

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.003	0.062	-9999	-1.2	1	1
VDR	-0.003	0.1	-9999	-0.51	21	21
FAM120B	0.016	0.033	-9999	-0.52	2	2
RXRs/LXRs/DNA/9cRA	0.012	0.13	-9999	-0.41	22	22
RXRs/LXRs/DNA/Oxysterols	-0.001	0.18	-9999	-0.44	68	68
MED1	0	0.067	-9999	-0.25	34	34
mol:9cRA	-0.001	0.021	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.003	0.11	-9999	-0.43	16	16
RXRs/NUR77	0.031	0.076	-9999	-0.28	19	19
RXRs/PPAR	0.008	0.093	-9999	-0.33	19	19
NCOR2	0.018	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.075	-9999	-0.37	21	21
RARs/VDR/DNA/Vit D3	0.004	0.095	-9999	-0.27	47	47
RARA	0.011	0.057	-9999	-0.4	9	9
NCOA1	0.012	0.057	-9999	-0.52	6	6
VDR/VDR/DNA	-0.003	0.1	-9999	-0.51	21	21
RARs/RARs/DNA/9cRA	0.005	0.077	-9999	-0.27	29	29
RARG	0.017	0.023	-9999	-0.52	1	1
RPS6KB1	0.004	0.055	-9999	-0.4	1	1
RARs/THRs/DNA/SMRT	0	0.1	-9999	-0.27	57	57
THRA	-0.01	0.11	-9999	-0.38	37	37
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.002	0.075	-9999	-0.37	21	21
RXRs/PPAR/9cRA/PGJ2/DNA	0.022	0.084	-9999	-0.29	18	18
NR1H4	0.015	0.031	-9999	-0.32	4	4
RXRs/LXRs/DNA	0.037	0.11	-9999	-0.42	10	10
NR1H2	0.018	0.017	-9999	-10000	0	0
NR1H3	0.008	0.07	-9999	-0.44	11	11
RXRs/VDR/DNA/Vit D3	0.021	0.088	-9999	-0.27	37	37
NR4A1	0.01	0.049	-9999	-0.27	15	15
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.016	0.063	-9999	-0.26	9	9
RXRG	0.004	0.084	-9999	-0.47	15	15
RXR alpha/CCPG	0.023	0.041	-9999	-0.38	5	5
RXRA	0.014	0.045	-9999	-0.54	3	3
RXRB	0.014	0.045	-9999	-0.52	3	3
THRB	-0.001	0.097	-9999	-0.48	20	20
PPARG	-0.036	0.14	-9999	-0.33	81	81
PPARD	0.017	0.017	-9999	-0.25	2	2
TNF	-0.01	0.23	-9999	-0.8	28	28
mol:Oxysterols	0	0.018	-9999	-10000	0	0
cholesterol transport	0	0.18	-9999	-0.43	68	68
PPARA	0.012	0.047	-9999	-0.31	10	10
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.025	0.13	-9999	-0.36	60	60
RXRs/NUR77/BCL2	-0.04	0.12	-9999	-0.24	130	130
SREBF1	-0.052	0.33	-9999	-1	51	51
RXRs/RXRs/DNA/9cRA	0.022	0.084	-9999	-0.29	18	18
ABCA1	-0.01	0.24	-9999	-0.84	28	28
RARs/THRs	0.001	0.12	-9999	-0.29	57	57
RXRs/FXR	0.034	0.074	-9999	-0.28	20	20
BCL2	-0.11	0.22	-9999	-0.47	144	144

×

Regulation of Androgen receptor activity

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.025	0.017	-9999	-0.37	1	1
SMARCC1	-0.003	0.12	-9999	-1.3	4	4
REL	0	0.087	-9999	-0.41	21	21
HDAC7	-0.025	0.13	-9999	-0.39	30	30
JUN	-0.033	0.15	-9999	-0.46	57	57
EP300	0.014	0.047	-9999	-0.52	4	4
KAT2B	0	0	-9999	-10000	0	0
KAT5	0	0	-9999	-10000	0	0
MAPK14	0.002	0.084	-9999	-0.38	20	20
FOXO1	0.001	0.092	-9999	-0.46	19	19
T-DHT/AR	-0.019	0.15	-9999	-0.41	30	30
MAP2K6	-0.013	0.11	-9999	-0.4	37	37
BRM/BAF57	0.026	0.028	-9999	-0.37	2	2
MAP2K4	-0.007	0.1	-9999	-0.39	31	31
SMARCA2	0.016	0.033	-9999	-0.52	2	2
PDE9A	-0.026	0.16	-9999	-0.71	14	14
NCOA2	0.01	0.063	-9999	-0.4	11	11
CEBPA	0.004	0.084	-9999	-0.5	14	14
EHMT2	0.018	0.001	-9999	-10000	0	0
cell proliferation	0.007	0.13	-9999	-0.37	20	20
NR0B1	-0.01	0.087	-9999	-0.27	51	51
EGR1	-0.1	0.2	-9999	-0.39	156	156
RXRs/9cRA	0.025	0.057	-9999	-0.28	18	18
AR/RACK1/Src	0.003	0.1	-9999	-0.34	20	20
AR/GR	-0.038	0.13	-9999	-0.29	73	73
GNB2L1	0.015	0.04	-9999	-0.52	3	3
PKN1	0.013	0.045	-9999	-0.39	6	6
RCHY1	0.002	0.09	-9999	-0.5	16	16
epidermal growth factor receptor activity	0	0.001	-9999	-0.005	6	6
MAPK8	0.004	0.08	-9999	-0.38	18	18
T-DHT/AR/TIF2/CARM1	0	0.11	-9999	-0.36	22	22
SRC	0.005	0.09	-9999	-0.32	18	18
NR3C1	-0.001	0.098	-9999	-0.51	19	19
KLK3	-0.038	0.11	-9999	-0.49	2	2
APPBP2	0.009	0.042	-9999	-0.25	13	13
TRIM24	0.017	0.024	-9999	-0.25	4	4
T-DHT/AR/TIP60	-0.021	0.1	-9999	-0.31	42	42
TMPRSS2	-0.18	0.43	-9999	-1.1	95	95
RXRG	0.004	0.083	-9999	-0.47	15	15
mol:9cRA	0	0	-9999	-0.003	2	2
RXRA	0.015	0.04	-9999	-0.52	3	3
RXRB	0.015	0.04	-9999	-0.52	3	3
CARM1	0.015	0.039	-9999	-0.36	5	5
NR2C2	0.016	0.02	-9999	-0.25	3	3
KLK2	0.021	0.095	-9999	-0.4	4	4
AR	-0.04	0.13	-9999	-0.28	104	104
SENP1	0.018	0	-9999	-10000	0	0
HSP90AA1	0.013	0.045	-9999	-0.39	6	6
MDM2	0.009	0.044	-9999	-0.26	14	14
SRY	0.001	0.085	-9999	-0.43	18	18
GATA2	-0.007	0.093	-9999	-0.31	40	40
MYST2	0.011	0.047	-9999	-0.31	10	10
HOXB13	-0.074	0.13	-9999	-0.25	182	182
T-DHT/AR/RACK1/Src	-0.002	0.11	-9999	-0.35	20	20
positive regulation of transcription	-0.007	0.093	-9999	-0.31	40	40
DNAJA1	0.012	0.043	-9999	-0.46	4	4
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.06	-9999	-0.31	16	16
NCOA1	0.016	0.063	-9999	-0.55	6	6
SPDEF	-0.081	0.21	-9999	-0.52	98	98
T-DHT/AR/TIF2	0.009	0.08	-9999	-0.3	11	11
T-DHT/AR/Hsp90	-0.012	0.11	-9999	-0.36	21	21
GSK3B	0.018	0.003	-9999	-10000	0	0
NR2C1	0.01	0.062	-9999	-0.52	7	7
mol:T-DHT	-0.002	0.095	-9999	-0.3	36	36
SIRT1	0.016	0.029	-9999	-0.34	3	3
ZMIZ2	0.016	0.002	-9999	-10000	0	0
POU2F1	0.014	0.038	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.022	0.12	-9999	-0.36	26	26
CREBBP	0.016	0.033	-9999	-0.52	2	2
SMARCE1	0.017	0.021	-9999	-0.26	3	3

×

Sphingosine 1-phosphate (S1P) pathway

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
SPHK2	0.017	0.023	-9999	-0.52	1	1
SPHK1	-0.027	0.14	-9999	-0.42	54	54
GNAI2	0.006	0.075	-9999	-0.48	12	12
mol:S1P	-0.001	0.087	-9999	-0.3	35	35
GNAO1	0.016	0.024	-9999	-0.25	4	4
mol:Sphinganine-1-P	-0.007	0.1	-9999	-0.38	33	33
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.015	0.075	-9999	-0.39	8	8
GNAI3	0.018	0	-9999	-10000	0	0
G12/G13	0.021	0.039	-9999	-0.37	4	4
S1PR3	0	0	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	-0.019	0.12	-9999	-0.4	46	46
S1P1/S1P	-0.012	0.11	-9999	-0.29	57	57
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
GNAI1	-0.017	0.12	-9999	-0.38	46	46
S1P/S1P5/G12	0.008	0.07	-9999	-0.23	35	35
S1P/S1P3/Gq	-0.026	0.11	-9999	-0.28	61	61
S1P/S1P4/Gi	0.006	0.087	-9999	-0.36	14	14
GNAQ	0	0	-9999	-10000	0	0
GNAZ	0.001	0.088	-9999	-0.44	19	19
GNA14	-0.079	0.18	-9999	-0.35	140	140
GNA15	0.002	0.076	-9999	-0.34	23	23
GNA12	0.018	0	-9999	-10000	0	0
GNA13	0.011	0.055	-9999	-0.36	10	10
GNA11	0.014	0.047	-9999	-0.52	4	4
ABCC1	0.012	0.051	-9999	-0.41	7	7

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0	0.1	-9999	-0.36	30	30
PDGFRB	0.01	0.067	-9999	-0.53	8	8
SPHK1	-0.054	0.19	-9999	-0.76	33	33
mol:S1P	-0.049	0.17	-9999	-0.65	35	35
S1P1/S1P/Gi	-0.002	0.15	-9999	-0.52	22	22
GNAO1	0.016	0.024	-9999	-0.26	4	4
PDGFB-D/PDGFRB/PLCgamma1	0.008	0.14	-9999	-0.51	19	19
PLCG1	0.004	0.14	-9999	-0.49	21	21
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.01	0.067	-9999	-0.53	8	8
GNAI2	0.007	0.076	-9999	-0.48	12	12
GNAI3	0.018	0.003	-9999	-10000	0	0
GNAI1	-0.016	0.12	-9999	-0.38	46	46
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.012	0.16	-9999	-0.6	30	30
S1P1/S1P	-0.026	0.19	-9999	-0.51	56	56
negative regulation of cAMP metabolic process	-0.001	0.14	-9999	-0.5	22	22
MAPK3	0.002	0.16	-9999	-0.54	21	21
calcium-dependent phospholipase C activity	0	0.003	-9999	-10000	0	0
Rac1/GDP	0.013	0	-9999	-10000	0	0
RhoA/GDP	0.004	0.058	-9999	-0.38	12	12
KDR	0.006	0.076	-9999	-0.65	5	5
PLCB2	-0.015	0.17	-9999	-0.45	55	55
RAC1	0.018	0	-9999	-10000	0	0
RhoA/GTP	-0.061	0.14	-9999	-0.42	58	58
receptor internalization	-0.024	0.17	-9999	-0.47	56	56
PTGS2	-0.001	0.17	-9999	-0.77	12	12
Rac1/GTP	-0.056	0.14	-9999	-0.42	55	55
RHOA	0.005	0.08	-9999	-0.52	12	12
VEGFA	-0.006	0.085	-9999	-0.29	31	31
negative regulation of T cell proliferation	-0.001	0.14	-9999	-0.5	22	22
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.002	0.088	-9999	-0.44	19	19
MAPK1	0.002	0.16	-9999	-0.54	21	21
S1P1/S1P/PDGFB-D/PDGFRB	-0.016	0.2	-9999	-0.5	56	56
ABCC1	0.012	0.051	-9999	-0.41	7	7

×

Angiopoietin receptor Tie2-mediated 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
AKT1	0.041	0.17	-10000	0	-0.9	12	12
NCK1/PAK1/Dok-R	-0.032	0.083	-10000	0	-0.43	13	13
NCK1/Dok-R	0.029	0.18	-10000	0	-1.1	11	11
PIK3CA	0.015	0.029	-10000	0	-0.34	3	3
mol:beta2-estradiol	-0.009	0.02	0.24	1	-10000	0	1
RELA	0.018	0	-10000	0	-10000	0	0
SHC1	0.017	0.024	-10000	0	-0.52	1	1
Rac/GDP	0.013	0	-10000	0	-10000	0	0
F2	0.006	0.021	0.26	1	-10000	0	1
TNIP2	0.012	0.052	-10000	0	-0.39	8	8
NF kappa B/RelA	0.052	0.15	-10000	0	-0.9	11	11
FN1	-0.048	0.17	-10000	0	-0.46	73	73
PLD2	0.037	0.16	-10000	0	-1	11	11
PTPN11	0.017	0.023	-10000	0	-0.52	1	1
GRB14	-0.16	0.21	-10000	0	-0.36	247	247
ELK1	0.046	0.15	-10000	0	-0.92	11	11
GRB7	-0.017	0.1	-10000	0	-0.29	59	59
PAK1	-0.022	0.13	-10000	0	-0.37	54	54
Tie2/Ang1/alpha5/beta1 Integrin	0.022	0.19	-10000	0	-0.98	12	12
CDKN1A	0.02	0.2	-10000	0	-0.76	28	28
ITGA5	0.015	0.035	-10000	0	-0.43	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.026	0.18	-10000	0	-1	12	12
CRK	0.016	0.033	-10000	0	-0.52	2	2
mol:NO	0.05	0.14	-10000	0	-0.66	12	12
PLG	0.039	0.16	-10000	0	-1	11	11
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.048	0.16	-10000	0	-0.87	11	11
GRB2	0.016	0.024	-10000	0	-0.25	4	4
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
ANGPT2	-0.018	0.16	-10000	0	-0.82	8	8
BMX	0.012	0.19	-10000	0	-1.2	11	11
ANGPT1	0.021	0.085	-10000	0	-1.2	1	1
tube development	0.026	0.17	-10000	0	-0.71	18	18
ANGPT4	0.017	0.026	-10000	0	-0.39	2	2
response to hypoxia	0.003	0.011	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.045	0.19	-10000	0	-1.1	11	11
alpha5/beta1 Integrin	0.022	0.041	-10000	0	-0.37	5	5
FGF2	-0.065	0.16	-10000	0	-0.34	122	122
STAT5A (dimer)	0.026	0.21	-10000	0	-0.78	26	26
mol:L-citrulline	0.05	0.14	-10000	0	-0.66	12	12
AGTR1	-0.15	0.21	-10000	0	-0.36	231	231
MAPK14	0.035	0.18	-10000	0	-1.1	11	11
Tie2/SHP2	0.027	0.16	-10000	0	-1	11	11
TEK	0.024	0.18	-10000	0	-0.94	14	14
RPS6KB1	0.04	0.16	-10000	0	-0.88	11	11
Angiotensin II/AT1	-0.099	0.15	-10000	0	-0.25	231	231
Tie2/Ang1/GRB2	0.04	0.16	-10000	0	-1	11	11
MAPK3	0.043	0.15	-10000	0	-0.92	11	11
MAPK1	0.042	0.15	-10000	0	-0.92	11	11
Tie2/Ang1/GRB7	0.025	0.17	-10000	0	-1	11	11
NFKB1	0.017	0.023	-10000	0	-0.52	1	1
MAPK8	0.038	0.16	-10000	0	-1	11	11
PI3K	0.035	0.19	-10000	0	-1.1	11	11
FES	0.031	0.19	-10000	0	-1.1	12	12
Crk/Dok-R	0.031	0.18	-10000	0	-1	11	11
Tie2/Ang1/ABIN2	0.038	0.16	-10000	0	-1	11	11
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.043	0.16	-10000	0	-0.8	12	12
STAT5A	0.011	0.056	-10000	0	-0.42	8	8
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.043	0.16	-10000	0	-0.88	11	11
Tie2/Ang2	0.015	0.22	-10000	0	-1	16	16
Tie2/Ang1	0.034	0.17	-10000	0	-1.1	11	11
FOXO1	0.043	0.17	-10000	0	-0.77	16	16
ELF1	0.017	0.073	-10000	0	-0.49	10	10
ELF2	0.037	0.16	-10000	0	-1	11	11
mol:Choline	0.038	0.16	-10000	0	-0.96	11	11
cell migration	-0.023	0.051	-10000	0	-0.22	20	20
FYN	0.023	0.19	-10000	0	-0.83	17	17
DOK2	-0.021	0.13	-10000	0	-0.4	48	48
negative regulation of cell cycle	0.024	0.18	-10000	0	-0.67	28	28
ETS1	0.011	0.075	-10000	0	-0.3	24	24
PXN	0.05	0.14	-10000	0	-0.72	11	11
ITGB1	0.014	0.044	-10000	0	-0.41	5	5
NOS3	0.049	0.15	-10000	0	-0.75	12	12
RAC1	0.018	0	-10000	0	-10000	0	0
TNF	0.004	0.097	-10000	0	-0.35	32	32
MAPKKK cascade	0.038	0.16	-10000	0	-0.96	11	11
RASA1	0.004	0.078	-10000	0	-0.42	16	16
Tie2/Ang1/Shc	0.041	0.16	-10000	0	-1	11	11
NCK1	0.011	0.045	-10000	0	-0.28	12	12
vasculogenesis	0.051	0.13	-10000	0	-0.59	12	12
mol:Phosphatidic acid	0.038	0.16	-10000	0	-0.96	11	11
mol:Angiotensin II	0.002	0.002	-10000	0	-10000	0	0
mol:NADP	0.05	0.14	-10000	0	-0.66	12	12
Rac1/GTP	-0.011	0.14	-10000	0	-0.82	11	11
MMP2	0.016	0.19	-10000	0	-1.1	11	11

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.015	0.034	-10000	0	-0.32	4	4
RAS family/GTP	0.002	0.099	-10000	0	-0.31	28	28
NFATC4	0.007	0.079	-10000	0	-0.32	11	11
ERBB2IP	0.017	0.023	-10000	0	-0.52	1	1
HSP90 (dimer)	0.013	0.045	-10000	0	-0.39	6	6
mammary gland morphogenesis	-0.01	0.094	-10000	0	-0.28	38	38
JUN	0.02	0.072	-10000	0	-10000	0	0
HRAS	0.012	0.051	-10000	0	-0.41	7	7
DOCK7	-0.002	0.092	-10000	0	-0.37	11	11
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.013	0.1	-10000	0	-0.3	48	48
AKT1	0.008	0.038	-10000	0	-0.26	9	9
BAD	0.016	0.035	-10000	0	-0.31	5	5
MAPK10	0.003	0.069	-10000	0	-0.21	22	22
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.01	0.1	-10000	0	-0.3	38	38
RAF1	0.006	0.1	-10000	0	-0.32	25	25
ErbB2/ErbB3/neuregulin 2	-0.037	0.12	-10000	0	-0.34	57	57
STAT3	0.016	0.095	-10000	0	-0.95	5	5
cell migration	0.009	0.07	-10000	0	-0.21	16	16
mol:PI-3-4-5-P3	0	0.002	-10000	0	-10000	0	0
cell proliferation	-0.045	0.24	-10000	0	-0.6	59	59
FOS	-0.059	0.22	-10000	0	-0.45	105	105
NRAS	0.005	0.076	-10000	0	-0.4	16	16
mol:Ca2+	-0.01	0.094	-10000	0	-0.28	38	38
MAPK3	-0.021	0.19	-10000	0	-0.47	54	54
MAPK1	-0.021	0.19	-10000	0	-0.46	57	57
JAK2	-0.004	0.096	-10000	0	-0.32	24	24
NF2	0.003	0.01	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.001	0.082	-10000	0	-0.27	39	39
NRG1	0.007	0.053	-10000	0	-0.27	18	18
GRB2/SOS1	0.024	0.023	-10000	0	-0.37	1	1
MAPK8	-0.001	0.089	-10000	0	-0.26	40	40
MAPK9	0.008	0.067	-10000	0	-0.22	17	17
ERBB2	-0.03	0.082	-10000	0	-0.22	71	71
ERBB3	-0.019	0.14	-10000	0	-0.52	36	36
SHC1	0.016	0.023	-10000	0	-0.52	1	1
RAC1	0.018	0	-10000	0	-10000	0	0
apoptosis	-0.01	0.041	0.35	5	-10000	0	5
STAT3 (dimer)	0.016	0.093	-10000	0	-0.93	5	5
RNF41	0.02	0.031	-10000	0	-0.28	4	4
FRAP1	0.016	0.032	-10000	0	-0.31	4	4
RAC1-CDC42/GTP	-0.022	0.055	-10000	0	-0.27	10	10
ErbB2/ErbB2/HSP90 (dimer)	-0.015	0.074	-10000	0	-0.32	18	18
CHRNA1	-0.008	0.16	-10000	0	-0.4	50	50
myelination	0.014	0.079	-10000	0	-0.32	11	11
PPP3CB	-0.001	0.086	-10000	0	-0.37	9	9
KRAS	0.009	0.065	-10000	0	-0.44	10	10
RAC1-CDC42/GDP	0.021	0.074	-10000	0	-0.29	10	10
NRG2	-0.017	0.1	-10000	0	-0.3	57	57
mol:GDP	0.001	0.082	-10000	0	-0.27	39	39
SOS1	0.017	0.023	-10000	0	-0.52	1	1
MAP2K2	0.006	0.11	-10000	0	-0.33	25	25
SRC	0.015	0.035	-10000	0	-0.43	3	3
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	0	0.091	-10000	0	-0.29	22	22
MAP2K1	-0.024	0.17	-10000	0	-0.52	17	17
heart morphogenesis	-0.01	0.094	-10000	0	-0.28	38	38
RAS family/GDP	0.013	0.099	-10000	0	-0.3	27	27
GRB2	0.015	0.024	-10000	0	-0.25	4	4
PRKACA	-0.001	0.005	-10000	0	-10000	0	0
CHRNE	0.016	0.019	-10000	0	-10000	0	0
HSP90AA1	0.013	0.045	-10000	0	-0.39	6	6
activation of caspase activity	-0.008	0.038	0.26	9	-10000	0	9
nervous system development	-0.01	0.094	-10000	0	-0.28	38	38
CDC42	0.018	0	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0.015	0.035	-10000	0	-0.43	3	3
MKNK1	0.018	0	-10000	0	-10000	0	0
mol:PIP3	-0.037	0.11	0.25	10	-0.28	70	80
FRAP1	0.015	0.034	-10000	0	-10000	0	0
AKT1	-0.011	0.1	0.22	8	-0.25	70	78
INSR	0.015	0.037	-10000	0	-0.39	4	4
Insulin Receptor/Insulin	0.021	0.027	-10000	0	-0.31	3	3
mol:GTP	0.004	0.085	-10000	0	-0.3	14	14
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.01	0.027	-10000	0	-0.18	1	1
TSC2	0.016	0.026	-10000	0	-0.39	2	2
RHEB/GDP	-0.026	0.062	-10000	0	-0.27	14	14
TSC1	0.018	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.022	0.12	-10000	0	-0.33	62	62
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.011	0.031	-10000	0	-0.19	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.017	0.012	-10000	0	-0.25	1	1
RPS6KB1	0.01	0.065	-10000	0	-0.26	5	5
MAP3K5	-0.014	0.089	-10000	0	-0.28	47	47
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
apoptosis	-0.014	0.089	-10000	0	-0.28	47	47
mol:LY294002	0	0.001	0.001	1	-0.001	57	58
EIF4B	0.016	0.062	-10000	0	-0.24	7	7
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.02	0.057	-10000	0	-0.26	2	2
eIF4E/eIF4G1/eIF4A1	-0.002	0.014	-10000	0	-10000	0	0
KIAA1303	0.015	0.031	-10000	0	-0.32	4	4
PI3K	-0.02	0.12	-10000	0	-0.3	79	79
mTOR/RHEB/GTP/Raptor/GBL	0.032	0.054	0.18	8	-0.3	2	10
FKBP1A	0.017	0.017	-10000	0	-0.25	2	2
RHEB/GTP	0.009	0.076	-10000	0	-0.27	14	14
mol:Amino Acids	0	0.001	0.001	1	-0.001	57	58
FKBP12/Rapamycin	0.012	0.011	-10000	0	-0.17	2	2
PDPK1	-0.014	0.1	0.23	8	-0.26	70	78
EIF4E	0.018	0	-10000	0	-10000	0	0
ASK1/PP5C	-0.011	0.15	-10000	0	-0.59	30	30
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.035	0.056	-10000	0	-0.56	4	4
TSC1/TSC2	0.009	0.095	0.22	8	-0.32	14	22
tumor necrosis factor receptor activity	0	0.001	0.001	57	-0.001	1	58
RPS6	0.015	0.037	-10000	0	-0.39	4	4
PPP5C	0.012	0.052	-10000	0	-0.39	8	8
EIF4G1	0.014	0.047	-10000	0	-0.52	4	4
IRS1	-0.034	0.12	-10000	0	-0.36	61	61
INS	0.017	0.023	-10000	0	-0.52	1	1
PTEN	-0.002	0.1	-10000	0	-0.52	19	19
PDK2	-0.02	0.11	0.23	8	-0.27	76	84
EIF4EBP1	-0.012	0.16	-10000	0	-1.1	10	10
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
PPP2R5D	0.021	0.033	-10000	0	-10000	0	0
peptide biosynthetic process	0.025	0.03	-10000	0	-0.28	5	5
RHEB	0.016	0.026	-10000	0	-0.39	2	2
EIF4A1	0.018	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.003	15	-0.002	7	22
EEF2	0.025	0.031	-10000	0	-0.28	5	5
eIF4E/4E-BP1	-0.001	0.14	-10000	0	-1	10	10

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	-0.009	0.14	-9999	-0.38	56	56
VEGFR1 homodimer/NRP1	-0.021	0.14	-9999	-0.39	56	56
mol:DAG	-0.004	0.14	-9999	-0.61	14	14
VEGFR1 homodimer/NRP1/VEGFR 121	-0.017	0.14	-9999	-0.35	59	59
CaM/Ca2+	0.006	0.13	-9999	-0.63	12	12
HIF1A	-0.035	0.17	-9999	-0.46	67	67
GAB1	0.006	0.074	-9999	-0.43	14	14
AKT1	-0.001	0.14	-9999	-0.54	19	19
PLCG1	-0.004	0.14	-9999	-0.62	14	14
NOS3	0.018	0.12	-9999	-0.54	14	14
CBL	0.017	0.012	-9999	-0.25	1	1
mol:NO	0.019	0.12	-9999	-0.52	14	14
FLT1	-0.021	0.16	-9999	-0.45	56	56
PGF	0.012	0.051	-9999	-0.41	7	7
VEGFR1 homodimer/NRP2/VEGFR121	-0.01	0.14	-9999	-0.64	15	15
CALM1	0.018	0	-9999	-10000	0	0
PIK3CA	0.016	0.029	-9999	-0.34	3	3
eNOS/Hsp90	0.026	0.12	-9999	-0.5	14	14
endothelial cell proliferation	0	0.13	-9999	-0.6	14	14
mol:Ca2+	-0.004	0.13	-9999	-0.61	14	14
MAPK3	0.007	0.12	-9999	-0.57	13	13
MAPK1	0.007	0.12	-9999	-0.58	12	12
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
PLGF homodimer	0.012	0.051	-9999	-0.41	7	7
PRKACA	0.018	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.001	0.083	-9999	-0.33	29	29
VEGFA homodimer	0	0.075	-9999	-0.29	31	31
VEGFR1 homodimer/VEGFA homodimer	-0.019	0.15	-9999	-0.38	59	59
platelet activating factor biosynthetic process	0.012	0.12	-9999	-0.55	13	13
PI3K	-0.004	0.15	-9999	-0.59	17	17
PRKCA	0.001	0.13	-9999	-0.61	12	12
PRKCB	-0.005	0.13	-9999	-0.57	14	14
VEGFR1 homodimer/PLGF homodimer	-0.012	0.15	-9999	-0.38	59	59
VEGFA	0	0.075	-9999	-0.29	31	31
VEGFB	0.017	0.023	-9999	-0.52	1	1
mol:IP3	-0.004	0.14	-9999	-0.61	14	14
RASA1	-0.008	0.14	-9999	-0.62	15	15
NRP2	0.011	0.052	-9999	-0.33	11	11
VEGFR1 homodimer	-0.021	0.16	-9999	-0.45	56	56
VEGFB homodimer	0.017	0.023	-9999	-0.52	1	1
NCK1	0.011	0.045	-9999	-0.28	12	12
eNOS/Caveolin-1	0.02	0.13	-9999	-0.53	16	16
PTPN11	0.017	0.023	-9999	-0.52	1	1
mol:PI-3-4-5-P3	-0.005	0.14	-9999	-0.58	17	17
mol:L-citrulline	0.019	0.12	-9999	-0.52	14	14
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.004	0.13	-9999	-0.6	14	14
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.009	0.14	-9999	-0.65	14	14
CD2AP	0.016	0.029	-9999	-0.34	3	3
PI3K/GAB1	-0.001	0.14	-9999	-0.56	17	17
PDPK1	-0.003	0.13	-9999	-0.56	16	16
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.007	0.14	-9999	-0.63	14	14
mol:NADP	0.019	0.12	-9999	-0.52	14	14
HSP90AA1	0.013	0.045	-9999	-0.39	6	6
ubiquitin-dependent protein catabolic process	0.003	0.13	-9999	-0.59	14	14
VEGFR1 homodimer/NRP2	-0.013	0.15	-9999	-0.39	57	57

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.008	0.081	-9999	-0.3	22	22
BIRC5	-0.037	0.15	-9999	-0.41	67	67
NFKBIA	0.024	0.054	-9999	-0.33	3	3
CPEB1	0.003	0.071	-9999	-0.31	23	23
AKT1	0.022	0.057	-9999	-0.3	4	4
NDEL1	0.018	0	-9999	-10000	0	0
Aurora A/BRCA1	0.013	0.067	-9999	-0.28	16	16
NDEL1/TACC3	0.021	0.079	-9999	-0.36	16	16
GADD45A	-0.011	0.11	-9999	-0.39	38	38
GSK3B	0.021	0.015	-9999	-10000	0	0
PAK1/Aurora A	0.002	0.087	-9999	-0.3	25	25
MDM2	0.011	0.044	-9999	-0.25	14	14
JUB	-0.027	0.15	-9999	-0.49	47	47
TPX2	-0.009	0.11	-9999	-0.37	40	40
TP53	0.004	0.089	-9999	-0.29	37	37
DLG7	-0.005	0.11	-9999	-0.35	43	43
AURKAIP1	0.016	0.029	-9999	-0.34	3	3
ARHGEF7	0.016	0.02	-9999	-0.25	3	3
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.022	0.083	-9999	-0.38	16	16
G2/M transition of mitotic cell cycle	0.013	0.066	-9999	-0.28	16	16
AURKA	0.021	0.058	-9999	-0.23	3	3
AURKB	-0.007	0.078	-9999	-0.22	46	46
CDC25B	0.011	0.069	-9999	-0.37	5	5
G2/M transition checkpoint	-0.002	0.088	-9999	-0.27	41	41
mRNA polyadenylation	0.015	0.054	-9999	-0.26	6	6
Aurora A/CPEB	0.016	0.055	-9999	-0.26	6	6
Aurora A/TACC1/TRAP/chTOG	0.016	0.093	-9999	-0.27	34	34
BRCA1	0	0.094	-9999	-0.48	19	19
centrosome duplication	0.002	0.087	-9999	-0.3	25	25
regulation of centrosome cycle	0.02	0.078	-9999	-0.35	16	16
spindle assembly	0.015	0.092	-9999	-0.27	34	34
TDRD7	0.004	0.084	-9999	-0.5	14	14
Aurora A/RasGAP/Survivin	-0.001	0.12	-9999	-0.3	57	57
CENPA	-0.016	0.12	-9999	-0.36	46	46
Aurora A/PP2A	0.025	0.047	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.008	0.088	-9999	-0.34	20	20
negative regulation of DNA binding	0.004	0.089	-9999	-0.29	37	37
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.023	0.028	-9999	-0.37	1	1
RASA1	0.004	0.078	-9999	-0.42	16	16
Ajuba/Aurora A	-0.002	0.089	-9999	-0.27	41	41
mitotic prometaphase	-0.001	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.058	-9999	-0.23	3	3
TACC1	-0.022	0.13	-9999	-0.41	49	49
TACC3	-0.006	0.11	-9999	-0.47	26	26
Aurora A/Antizyme1	0.034	0.044	-9999	-0.27	1	1
Aurora A/RasGAP	0.018	0.066	-9999	-0.3	11	11
OAZ1	0.018	0	-9999	-10000	0	0
RAN	0.017	0.012	-9999	-0.25	1	1
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.021	0.015	-9999	-10000	0	0
GIT1	0.014	0.035	-9999	-0.3	6	6
GIT1/beta-PIX/PAK1	0.009	0.084	-9999	-0.32	24	24
Importin alpha/Importin beta/TPX2	-0.009	0.11	-9999	-0.37	40	40
PPP2R5D	0.016	0.02	-9999	-0.25	3	3
Aurora A/TPX2	0.006	0.1	-9999	-0.4	26	26
PAK1	-0.022	0.13	-9999	-0.37	54	54
CKAP5	0.017	0.017	-9999	-0.25	2	2

×

Arf6 downstream 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
PLAUR	-0.022	0.26	-10000	0	-1.1	30	30
regulation of axonogenesis	-0.012	0.065	0.35	8	-10000	0	8
myoblast fusion	0.003	0.1	0.4	31	-10000	0	31
mol:GTP	-0.002	0.062	-10000	0	-0.24	32	32
regulation of calcium-dependent cell-cell adhesion	-0.018	0.082	0.33	13	-10000	0	13
ARF1/GTP	0.012	0.05	-10000	0	-0.32	3	3
mol:GM1	0	0.047	-10000	0	-0.25	4	4
mol:Choline	0.007	0.075	-10000	0	-0.34	16	16
lamellipodium assembly	-0.001	0.11	-10000	0	-0.43	32	32
MAPK3	0.009	0.089	-10000	0	-0.33	33	33
ARF6/GTP/NME1/Tiam1	0.019	0.083	-10000	0	-0.33	13	13
ARF1	0.017	0.023	-10000	0	-0.52	1	1
ARF6/GDP	-0.003	0.1	-10000	0	-0.4	31	31
ARF1/GDP	0.006	0.097	-10000	0	-0.36	33	33
ARF6	0.007	0.05	-10000	0	-0.62	2	2
RAB11A	0.016	0.029	-10000	0	-0.34	3	3
TIAM1	0.007	0.074	-10000	0	-0.44	13	13
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.009	0.09	-10000	0	-0.33	34	34
actin filament bundle formation	0.001	0.11	0.35	41	-10000	0	41
KALRN	-0.022	0.078	-10000	0	-0.31	32	32
RAB11FIP3/RAB11A	0.019	0.05	-10000	0	-0.37	8	8
RhoA/GDP	-0.001	0.11	-10000	0	-0.36	41	41
NME1	0.012	0.039	-10000	0	-0.25	11	11
Rac1/GDP	0.005	0.096	-10000	0	-0.36	32	32
substrate adhesion-dependent cell spreading	-0.002	0.062	-10000	0	-0.24	32	32
cortical actin cytoskeleton organization	-0.002	0.11	-10000	0	-0.43	32	32
RAC1	0.018	0	-10000	0	-10000	0	0
liver development	-0.002	0.062	-10000	0	-0.24	32	32
ARF6/GTP	-0.002	0.062	-10000	0	-0.24	32	32
RhoA/GTP	0.004	0.074	-10000	0	-0.36	14	14
mol:GDP	-0.003	0.1	-10000	0	-0.4	32	32
ARF6/GTP/RAB11FIP3/RAB11A	0.019	0.058	-10000	0	-0.28	10	10
RHOA	0.005	0.08	-10000	0	-0.52	12	12
PLD1	0.001	0.078	-10000	0	-0.37	13	13
RAB11FIP3	0.01	0.063	-10000	0	-0.49	8	8
tube morphogenesis	-0.001	0.11	-10000	0	-0.43	32	32
ruffle organization	0.012	0.065	-10000	0	-0.35	8	8
regulation of epithelial cell migration	-0.002	0.062	-10000	0	-0.24	32	32
PLD2	0.01	0.06	-10000	0	-0.38	6	6
PIP5K1A	0.012	0.065	-10000	0	-0.35	8	8
mol:Phosphatidic acid	0.007	0.075	-10000	0	-0.34	16	16
Rac1/GTP	-0.002	0.11	-10000	0	-0.44	32	32

×

HIF-2-alpha transcription factor network

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
MMP14	-0.054	0.27	-10000	0	-1.2	28	28
oxygen homeostasis	0.007	0.013	-10000	0	-10000	0	0
TCEB2	0.018	0	-10000	0	-10000	0	0
TCEB1	0.014	0.035	-10000	0	-0.3	6	6
VHL/Elongin B/Elongin C/HIF2A	0.035	0.13	-10000	0	-0.36	24	24
EPO	0.051	0.23	-10000	0	-0.58	27	27
FIH (dimer)	0.024	0.027	-10000	0	-0.52	1	1
APEX1	0.024	0.019	-10000	0	-0.26	1	1
SERPINE1	0.051	0.26	-10000	0	-0.7	31	31
FLT1	-0.023	0.2	-10000	0	-1.1	15	15
ADORA2A	0.041	0.25	-10000	0	-0.67	32	32
germ cell development	0.066	0.23	-10000	0	-0.62	26	26
SLC11A2	0.064	0.24	-10000	0	-0.66	27	27
BHLHE40	0.056	0.23	-10000	0	-0.62	31	31
HIF1AN	0.024	0.027	-10000	0	-0.53	1	1
HIF2A/ARNT/SIRT1	0.039	0.17	-10000	0	-0.43	30	30
ETS1	0.018	0.075	-10000	0	-0.3	24	24
CITED2	-0.013	0.15	-10000	0	-1.1	9	9
KDR	-0.01	0.15	-10000	0	-1.1	9	9
PGK1	0.066	0.23	-10000	0	-0.65	25	25
SIRT1	0.015	0.029	-10000	0	-0.35	3	3
response to hypoxia	-0.001	0.003	-10000	0	-10000	0	0
HIF2A/ARNT	0.082	0.27	-10000	0	-0.72	31	31
EPAS1	0.018	0.15	-10000	0	-0.38	36	36
SP1	0.023	0.027	-10000	0	-0.52	1	1
ABCG2	0.058	0.25	-10000	0	-0.69	30	30
EFNA1	0.056	0.25	-10000	0	-0.63	34	34
FXN	0.057	0.23	-10000	0	-0.65	25	25
POU5F1	0.066	0.23	-10000	0	-0.65	26	26
neuron apoptosis	-0.081	0.27	0.7	31	-10000	0	31
EP300	0.014	0.047	-10000	0	-0.52	4	4
EGLN3	-0.066	0.18	-10000	0	-0.39	116	116
EGLN2	0.018	0.054	-10000	0	-0.36	9	9
EGLN1	0.008	0.084	-10000	0	-0.35	24	24
VHL/Elongin B/Elongin C	0.032	0.027	-10000	0	-0.3	1	1
VHL	0.015	0.029	-10000	0	-0.25	6	6
ARNT	0.025	0.014	-10000	0	-10000	0	0
SLC2A1	0.051	0.24	-10000	0	-0.64	31	31
TWIST1	0.035	0.27	-10000	0	-0.71	41	41
ELK1	0.022	0.038	-10000	0	-0.38	4	4
HIF2A/ARNT/Cbp/p300	0.052	0.17	-10000	0	-0.44	28	28
VEGFA	0.058	0.24	-10000	0	-0.65	28	28
CREBBP	0.016	0.033	-10000	0	-0.52	2	2

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.011	0.056	-10000	0	-0.3	12	12
cell-cell adhesion	0.038	0.084	0.37	18	-10000	0	18
Ephrin B/EPHB2/RasGAP	0.023	0.087	-10000	0	-0.28	32	32
ITSN1	0.015	0.035	-10000	0	-0.43	3	3
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
SHC1	0.017	0.023	-10000	0	-0.52	1	1
Ephrin B1/EPHB3	0.006	0.072	-10000	0	-0.32	21	21
Ephrin B1/EPHB1	-0.003	0.07	-10000	0	-0.3	13	13
HRAS/GDP	-0.034	0.081	-10000	0	-0.3	28	28
Ephrin B/EPHB1/GRB7	-0.003	0.097	-10000	0	-0.27	34	34
Endophilin/SYNJ1	0.018	0.065	-10000	0	-0.23	25	25
KRAS	0.009	0.065	-10000	0	-0.44	10	10
Ephrin B/EPHB1/Src	0.013	0.089	-10000	0	-0.28	26	26
endothelial cell migration	-0.006	0.11	-10000	0	-0.28	59	59
GRB2	0.016	0.024	-10000	0	-0.25	4	4
GRB7	-0.017	0.1	-10000	0	-0.29	59	59
PAK1	0.002	0.093	-10000	0	-0.26	29	29
HRAS	0.012	0.051	-10000	0	-0.41	7	7
RRAS	0.015	0.075	-10000	0	-0.25	32	32
DNM1	0.013	0.047	-10000	0	-0.37	7	7
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.005	0.079	-10000	0	-0.26	27	27
lamellipodium assembly	-0.038	0.084	-10000	0	-0.37	18	18
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.016	0.077	-10000	0	-0.47	5	5
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
EPHB2	0.007	0.061	-10000	0	-0.32	16	16
EPHB3	-0.005	0.1	-10000	0	-0.45	26	26
EPHB1	-0.022	0.1	-10000	0	-0.28	72	72
EPHB4	-0.013	0.12	-10000	0	-0.43	36	36
mol:GDP	0	0.1	-10000	0	-0.33	25	25
Ephrin B/EPHB2	0.019	0.07	-10000	0	-0.25	26	26
Ephrin B/EPHB3	0.012	0.086	-10000	0	-0.27	38	38
JNK cascade	0.006	0.082	-10000	0	-0.28	23	23
Ephrin B/EPHB1	0.005	0.084	-10000	0	-0.26	33	33
RAP1/GDP	0.013	0.099	-10000	0	-0.29	29	29
EFNB2	-0.008	0.11	-10000	0	-0.4	33	33
EFNB3	0.018	0	-10000	0	-10000	0	0
EFNB1	0.01	0.051	-10000	0	-0.3	13	13
Ephrin B2/EPHB1-2	-0.007	0.089	-10000	0	-0.28	34	34
RAP1B	0.013	0.044	-10000	0	-0.32	8	8
RAP1A	0.012	0.057	-10000	0	-0.52	6	6
CDC42/GTP	-0.031	0.076	-10000	0	-0.39	11	11
Rap1/GTP	-0.03	0.079	-10000	0	-0.4	14	14
axon guidance	0.011	0.056	-10000	0	-0.3	12	12
MAPK3	0.027	0.07	-10000	0	-0.42	5	5
MAPK1	0.027	0.071	-10000	0	-0.39	6	6
Rac1/GDP	0.01	0.095	-10000	0	-0.3	24	24
actin cytoskeleton reorganization	-0.035	0.074	-10000	0	-0.29	23	23
CDC42/GDP	0.01	0.095	-10000	0	-0.3	24	24
PI3K	-0.003	0.11	-10000	0	-0.28	59	59
EFNA5	0.006	0.068	-10000	0	-0.35	17	17
Ephrin B2/EPHB4	-0.01	0.1	-10000	0	-0.33	40	40
Ephrin B/EPHB2/Intersectin/N-WASP	0.02	0.069	-10000	0	-0.23	34	34
CDC42	0.018	0	-10000	0	-10000	0	0
RAS family/GTP	-0.035	0.077	-10000	0	-0.34	17	17
PTK2	0.006	0.034	-10000	0	-0.34	3	3
MAP4K4	0.006	0.083	-10000	0	-0.28	23	23
SRC	0.015	0.035	-10000	0	-0.43	3	3
KALRN	0.006	0.057	-10000	0	-0.27	21	21
Intersectin/N-WASP	0.019	0.054	-10000	0	-0.37	10	10
neuron projection morphogenesis	0.009	0.11	-10000	0	-0.34	23	23
MAP2K1	0.022	0.073	-10000	0	-0.44	5	5
WASL	0.01	0.066	-10000	0	-0.52	8	8
Ephrin B1/EPHB1-2/NCK1	0.011	0.081	-10000	0	-0.27	26	26
cell migration	0.026	0.077	-10000	0	-0.45	5	5
NRAS	0.005	0.076	-10000	0	-0.4	16	16
SYNJ1	0.019	0.066	-10000	0	-0.24	25	25
PXN	0.018	0	-10000	0	-10000	0	0
TF	0.019	0.066	-10000	0	-0.32	1	1
HRAS/GTP	0.004	0.092	-10000	0	-0.38	12	12
Ephrin B1/EPHB1-2	0.004	0.074	-10000	0	-0.27	22	22
cell adhesion mediated by integrin	0.012	0.062	0.26	23	-10000	0	23
RAC1	0.018	0	-10000	0	-10000	0	0
mol:GTP	0.008	0.097	-10000	0	-0.28	33	33
RAC1-CDC42/GTP	-0.034	0.08	-10000	0	-0.35	18	18
RASA1	0.004	0.078	-10000	0	-0.42	16	16
RAC1-CDC42/GDP	0.017	0.093	-10000	0	-0.29	23	23
ruffle organization	0.008	0.11	-10000	0	-0.38	17	17
NCK1	0.011	0.045	-10000	0	-0.28	12	12
receptor internalization	0.022	0.067	-10000	0	-0.32	2	2
Ephrin B/EPHB2/KALRN	0.024	0.078	-10000	0	-0.27	24	24
ROCK1	0.012	0.064	-10000	0	-0.28	21	21
RAS family/GDP	-0.035	0.077	-10000	0	-0.31	21	21
Rac1/GTP	-0.039	0.089	-10000	0	-0.39	18	18
Ephrin B/EPHB1/Src/Paxillin	0.013	0.077	-10000	0	-0.49	4	4

×

PDGFR-beta signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.012	0.14	-9999	-0.46	30	30
PDGFB-D/PDGFRB/SLAP	0.01	0.074	-9999	-0.38	17	17
PDGFB-D/PDGFRB/APS/CBL	0.018	0.042	-9999	-0.32	8	8
AKT1	-0.021	0.14	-9999	-0.39	34	34
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.006	0.13	-9999	-0.49	22	22
PIK3CA	0.016	0.029	-9999	-0.34	3	3
FGR	-0.008	0.065	-9999	-0.39	10	10
mol:Ca2+	0.004	0.11	-9999	-0.62	11	11
MYC	-0.029	0.22	-9999	-0.75	41	41
SHC1	0.017	0.023	-9999	-0.52	1	1
HRAS/GDP	0.02	0.069	-9999	-0.25	25	25
LRP1/PDGFRB/PDGFB	0.024	0.064	-9999	-0.35	13	13
GRB10	-0.003	0.097	-9999	-0.43	24	24
PTPN11	0.017	0.023	-9999	-0.52	1	1
GO:0007205	0.003	0.11	-9999	-0.63	11	11
PTEN	-0.002	0.1	-9999	-0.52	19	19
GRB2	0.016	0.024	-9999	-0.25	4	4
GRB7	-0.017	0.1	-9999	-0.29	59	59
PDGFB-D/PDGFRB/SHP2	0.019	0.052	-9999	-0.37	9	9
PDGFB-D/PDGFRB/GRB10	0.005	0.086	-9999	-0.37	24	24
cell cycle arrest	0.01	0.074	-9999	-0.37	17	17
HRAS	0.012	0.051	-9999	-0.41	7	7
HIF1A	-0.035	0.14	-9999	-0.35	44	44
GAB1	-0.011	0.13	-9999	-0.61	15	15
mol:GTP	0	0	-9999	-10000	0	0
DNM2	-0.008	0.13	-9999	-0.59	14	14
PDGFB-D/PDGFRB	0.019	0.067	-9999	-0.35	12	12
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.016	0.062	-9999	-0.37	13	13
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.017	0.15	-9999	-0.47	32	32
positive regulation of MAPKKK cascade	0.019	0.052	-9999	-0.37	9	9
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
mol:IP3	0.003	0.11	-9999	-0.64	11	11
E5	0	0.002	-9999	-10000	0	0
CSK	0.015	0.031	-9999	-0.32	4	4
PDGFB-D/PDGFRB/GRB7	-0.004	0.085	-9999	-0.37	16	16
SHB	0.008	0.067	-9999	-0.41	12	12
BLK	-0.024	0.091	-9999	-0.45	18	18
PTPN2	0.015	0.024	-9999	-0.26	4	4
PDGFB-D/PDGFRB/SNX15	0.019	0.05	-9999	-0.37	8	8
BCAR1	0.017	0.012	-9999	-0.25	1	1
VAV2	-0.011	0.14	-9999	-0.57	18	18
CBL	0.017	0.012	-9999	-0.25	1	1
PDGFB-D/PDGFRB/DEP1	0.015	0.063	-9999	-0.37	13	13
LCK	-0.082	0.2	-9999	-0.57	68	68
PDGFRB	0.009	0.067	-9999	-0.53	8	8
ACP1	0.013	0.052	-9999	-0.52	5	5
HCK	-0.029	0.14	-9999	-0.55	28	28
ABL1	-0.005	0.11	-9999	-0.49	17	17
PDGFB-D/PDGFRB/CBL	-0.01	0.14	-9999	-0.64	16	16
PTPN1	0.001	0.07	-9999	-0.28	28	28
SNX15	0.017	0.012	-9999	-0.25	1	1
STAT3	0.015	0.04	-9999	-0.52	3	3
STAT1	-0.02	0.12	-9999	-0.33	58	58
cell proliferation	-0.022	0.2	-9999	-0.65	42	42
SLA	0.004	0.078	-9999	-0.39	18	18
actin cytoskeleton reorganization	0.032	0.07	-9999	-0.37	7	7
SRC	-0.009	0.083	-9999	-0.47	11	11
PI3K	-0.066	0.12	-9999	-0.44	31	31
PDGFB-D/PDGFRB/GRB7/SHC	0.01	0.074	-9999	-0.31	17	17
SH2B2	0	0	-9999	-10000	0	0
PLCgamma1/SPHK1	-0.007	0.14	-9999	-0.52	21	21
LYN	-0.007	0.066	-9999	-0.38	11	11
LRP1	0.017	0.023	-9999	-0.52	1	1
SOS1	0.017	0.023	-9999	-0.52	1	1
STAT5B	0.016	0.026	-9999	-0.39	2	2
STAT5A	0.011	0.056	-9999	-0.42	8	8
NCK1-2/p130 Cas	0.033	0.062	-9999	-0.29	11	11
SPHK1	-0.027	0.14	-9999	-0.42	54	54
EDG1	-0.019	0.12	-9999	-0.4	46	46
mol:DAG	0.003	0.11	-9999	-0.64	11	11
PLCG1	0.003	0.11	-9999	-0.66	11	11
NHERF/PDGFRB	-0.038	0.15	-9999	-0.35	91	91
YES1	-0.016	0.096	-9999	-0.46	19	19
cell migration	-0.038	0.15	-9999	-0.35	91	91
SHC/Grb2/SOS1	0.036	0.06	-9999	-0.28	10	10
SLC9A3R2	-0.032	0.15	-9999	-0.49	52	52
SLC9A3R1	-0.043	0.16	-9999	-0.44	70	70
NHERF1-2/PDGFRB/PTEN	-0.033	0.16	-9999	-0.32	103	103
FYN	-0.017	0.14	-9999	-0.73	13	13
DOK1	0.013	0.074	-9999	-0.3	22	22
HRAS/GTP	0.009	0.036	-9999	-0.29	7	7
PDGFB	0.009	0.064	-9999	-0.39	12	12
RAC1	-0.011	0.16	-9999	-0.49	40	40
PRKCD	0.019	0.065	-9999	-0.32	14	14
FER	0.02	0.06	-9999	-0.3	13	13
MAPKKK cascade	-0.006	0.05	-9999	-0.29	8	8
RASA1	0.013	0.072	-9999	-0.29	22	22
NCK1	0.011	0.045	-9999	-0.28	12	12
NCK2	0.015	0.026	-9999	-0.25	5	5
p62DOK/Csk	0.023	0.071	-9999	-0.27	23	23
PDGFB-D/PDGFRB/SHB	0.013	0.071	-9999	-0.4	14	14
chemotaxis	-0.004	0.11	-9999	-0.47	17	17
STAT1-3-5/STAT1-3-5	-0.021	0.071	-9999	-0.4	6	6
Bovine Papilomavirus E5/PDGFRB	0.006	0.049	-9999	-0.39	8	8
PTPRJ	0.012	0.055	-9999	-0.44	7	7

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.018	0	-9999	-10000	0	0
VLDLR	-0.061	0.17	-9999	-0.4	100	100
LRPAP1	0.016	0.026	-9999	-0.39	2	2
NUDC	0.018	0	-9999	-10000	0	0
RELN/LRP8	-0.015	0.1	-9999	-0.31	43	43
CaM/Ca2+	0.013	0	-9999	-10000	0	0
KATNA1	0.015	0.033	-9999	-0.31	5	5
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.008	0.093	-9999	-0.28	43	43
IQGAP1/CaM	0.026	0	-9999	-10000	0	0
DAB1	0.018	0	-9999	-10000	0	0
IQGAP1	0.018	0	-9999	-10000	0	0
PLA2G7	-0.092	0.2	-9999	-0.41	137	137
CALM1	0.018	0	-9999	-10000	0	0
DYNLT1	0.018	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.027	0.11	-9999	-0.37	37	37
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.015	0.037	-9999	-0.39	4	4
CDK5R1	0.014	0.031	-9999	-0.25	7	7
LIS1/Poliovirus Protein 3A	0.018	0.02	-9999	-0.31	2	2
CDK5R2	0.017	0.017	-9999	-0.25	2	2
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.017	0.11	-9999	-0.31	59	59
YWHAE	0.016	0.029	-9999	-0.34	3	3
NDEL1/14-3-3 E	0.024	0.079	-9999	-0.29	4	4
MAP1B	-0.015	0.075	-9999	-0.29	34	34
RAC1	0.024	0.01	-9999	-10000	0	0
p35/CDK5	0.007	0.085	-9999	-0.33	3	3
RELN	0.01	0.059	-9999	-0.38	11	11
PAFAH/LIS1	-0.036	0.12	-9999	-0.3	80	80
LIS1/CLIP170	0.029	0.031	-9999	-0.3	4	4
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.016	0.043	-9999	-0.29	1	1
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	0.002	0.096	-9999	-0.24	62	62
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	0.016	0.08	-9999	-0.31	3	3
LIS1/IQGAP1	0.031	0.021	-9999	-0.3	2	2
RHOA	0.014	0.067	-9999	-0.42	12	12
PAFAH1B1	0.024	0.024	-9999	-0.37	2	2
PAFAH1B3	0.009	0.067	-9999	-0.49	9	9
PAFAH1B2	0.017	0.012	-9999	-0.25	1	1
MAP1B/LIS1/Dynein heavy chain	0.013	0.055	-9999	-0.31	2	2
NDEL1/Katanin 60/Dynein heavy chain	0.031	0.078	-9999	-10000	0	0
LRP8	-0.057	0.16	-9999	-0.34	110	110
NDEL1/Katanin 60	0.024	0.079	-9999	-0.29	3	3
P39/CDK5	0.008	0.084	-9999	-0.33	3	3
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.031	0.021	-9999	-0.3	2	2
CDK5	-0.001	0.087	-9999	-0.25	43	43
PPP2R5D	0.016	0.02	-9999	-0.25	3	3
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.025	0.026	-9999	-0.26	4	4
CSNK2A1	0.017	0.023	-9999	-0.52	1	1
RELN/VLDLR/DAB1/LIS1	0.003	0.1	-9999	-0.25	59	59
RELN/VLDLR	-0.045	0.14	-9999	-0.28	113	113
CDC42	0.024	0.01	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.02	0.089	-9999	-0.3	33	33
MAP4K1	0.012	0.04	-9999	-0.25	12	12
MAP3K8	-0.036	0.15	-9999	-0.39	70	70
PRKCB	0	0	-9999	-10000	0	0
DBNL	0.014	0.039	-9999	-0.36	5	5
CRKL	0.014	0.047	-9999	-0.52	4	4
MAP3K1	0.006	0.099	-9999	-0.35	12	12
JUN	-0.008	0.092	-9999	-0.28	47	47
MAP3K7	0.029	0.065	-9999	-0.28	6	6
GRAP2	0.012	0.042	-9999	-0.28	10	10
CRK	0.016	0.033	-9999	-0.52	2	2
MAP2K4	0.006	0.094	-9999	-0.35	15	15
LAT	0.002	0.068	-9999	-0.27	29	29
LCP2	-0.004	0.097	-9999	-0.4	27	27
MAPK8	0.011	0.052	-9999	-0.58	3	3
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.024	0.069	-9999	-0.3	6	6
LAT/GRAP2/SLP76/HPK1/HIP-55	0.026	0.087	-9999	-0.3	27	27

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.009	0.13	-10000	0	-0.51	12	12
BAG4	0.002	0.07	-10000	0	-0.28	28	28
BAD	0.012	0.045	-10000	0	-0.19	8	8
NFKBIA	0.014	0.042	-10000	0	-0.45	4	4
BIRC3	-0.085	0.19	-10000	0	-0.41	128	128
BAX	0.011	0.045	-10000	0	-0.19	7	7
EnzymeConsortium:3.1.4.12	0.002	0.03	-10000	0	-0.11	12	12
IKBKB	-0.003	0.12	-10000	0	-0.44	16	16
MAP2K2	0.023	0.046	-10000	0	-0.24	6	6
MAP2K1	0.024	0.043	-10000	0	-0.23	4	4
SMPD1	0.006	0.039	-10000	0	-0.19	9	9
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.002	0.12	-10000	0	-0.42	19	19
MAP2K4	-0.011	0.089	-10000	0	-0.24	55	55
protein ubiquitination	-0.003	0.12	-10000	0	-0.44	15	15
EnzymeConsortium:2.7.1.37	0.02	0.052	-10000	0	-0.24	5	5
response to UV	0	0	-10000	0	-0.002	4	4
RAF1	0.018	0.044	-10000	0	-0.22	4	4
CRADD	0.01	0.063	-10000	0	-0.49	8	8
mol:ceramide	0.005	0.046	-10000	0	-0.17	13	13
I-kappa-B-alpha/RELA/p50/ubiquitin	0.022	0.026	-10000	0	-0.31	3	3
MADD	0.018	0	-10000	0	-10000	0	0
MAP3K1	-0.009	0.083	-10000	0	-0.24	44	44
TRADD	0.016	0.026	-10000	0	-0.39	2	2
RELA/p50	0.018	0	-10000	0	-10000	0	0
MAPK3	0.027	0.044	-10000	0	-0.2	6	6
MAPK1	0.026	0.044	-10000	0	-0.2	6	6
p50/RELA/I-kappa-B-alpha	0.024	0.031	-10000	0	-0.37	3	3
FADD	-0.011	0.13	-10000	0	-0.44	19	19
KSR1	0.012	0.045	-10000	0	-0.19	7	7
MAPK8	-0.004	0.086	-10000	0	-0.22	54	54
TRAF2	0.014	0.042	-10000	0	-0.45	4	4
response to radiation	0	0	-10000	0	-0.002	1	1
CHUK	-0.007	0.13	-10000	0	-0.46	16	16
TNF R/SODD	0.014	0.054	-10000	0	-0.37	5	5
TNF	-0.004	0.094	-10000	0	-0.36	31	31
CYCS	0.036	0.056	0.14	65	-0.17	5	70
IKBKG	-0.001	0.12	-10000	0	-0.47	12	12
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.011	0.13	-10000	0	-0.52	12	12
RELA	0.018	0	-10000	0	-10000	0	0
RIPK1	0.017	0.023	-10000	0	-0.52	1	1
AIFM1	0.037	0.056	0.14	65	-0.17	5	70
TNF/TNF R/SODD	0.012	0.074	-10000	0	-0.31	18	18
TNFRSF1A	0.016	0.033	-10000	0	-0.52	2	2
response to heat	0	0	-10000	0	-0.002	1	1
CASP8	0.021	0.032	-10000	0	-10000	0	0
NSMAF	-0.007	0.13	-10000	0	-0.48	14	14
response to hydrogen peroxide	0	0	-10000	0	-0.002	4	4
BCL2	-0.11	0.22	-10000	0	-0.47	144	144

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	0.015	0.029	-9999	-0.25	6	6
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.018	0	-9999	-10000	0	0
TCEB1	0.014	0.035	-9999	-0.3	6	6
HIF1A/p53	-0.02	0.11	-9999	-0.32	37	37
HIF1A	-0.011	0.087	-9999	-0.32	20	20
COPS5	0.01	0.056	-9999	-0.35	11	11
VHL/Elongin B/Elongin C/RBX1/CUL2	0.049	0.025	-9999	-0.24	1	1
FIH (dimer)	0.017	0.023	-9999	-0.52	1	1
CDKN2A	-0.053	0.15	-9999	-0.33	108	108
ARNT/IPAS	0.024	0.02	-9999	-10000	0	0
HIF1AN	0.017	0.023	-9999	-0.52	1	1
GNB2L1	0.015	0.04	-9999	-0.52	3	3
HIF1A/ARNT	0	0.084	-9999	-0.3	20	20
CUL2	0.017	0.017	-9999	-0.25	2	2
OS9	0.014	0.04	-9999	-0.34	6	6
RACK1/Elongin B/Elongin C	0.032	0.033	-9999	-0.3	4	4
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.002	0.089	-9999	-0.31	22	22
PHD1-3/OS9	-0.021	0.12	-9999	-0.28	80	80
HIF1A/RACK1/Elongin B/Elongin C	0.013	0.083	-9999	-0.34	5	5
VHL	0.015	0.029	-9999	-0.25	6	6
HSP90AA1	0.013	0.045	-9999	-0.39	6	6
HIF1A/JAB1	-0.004	0.087	-9999	-0.29	22	22
EGLN3	-0.074	0.18	-9999	-0.4	116	116
EGLN2	0.011	0.053	-9999	-0.37	9	9
EGLN1	0.001	0.082	-9999	-0.35	24	24
TP53	-0.023	0.14	-9999	-0.48	43	43
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.034	0.033	-9999	-0.5	1	1
ARNT	0.018	0	-9999	-10000	0	0
ARD1A	0.016	0.02	-9999	-0.25	3	3
RBX1	0.018	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.032	0.11	-9999	-0.32	36	36

×

p38 MAPK signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.001	0.073	-9999	-0.26	34	34
TRAF2/ASK1	-0.002	0.085	-9999	-0.31	33	33
ATM	0.017	0.012	-9999	-0.25	1	1
MAP2K3	-0.011	0.12	-9999	-0.37	38	38
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.016	0.12	-9999	-0.3	54	54
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.003	0.083	-9999	-0.45	16	16
TXN	0.009	0.007	-9999	-10000	0	0
CALM1	0.018	0	-9999	-10000	0	0
GADD45A	-0.011	0.11	-9999	-0.39	38	38
GADD45B	-0.002	0.097	-9999	-0.44	23	23
MAP3K1	-0.03	0.14	-9999	-0.42	58	58
MAP3K6	0.015	0.035	-9999	-0.43	3	3
MAP3K7	0.016	0.02	-9999	-0.25	3	3
MAP3K4	0.018	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	-0.004	0.099	-9999	-0.37	33	33
TAK1/TAB family	0.01	0.038	-9999	-0.42	4	4
RAC1/OSM/MEKK3	0.034	0.006	-9999	-10000	0	0
TRAF2	0.014	0.042	-9999	-0.45	4	4
RAC1/OSM/MEKK3/MKK3	-0.029	0.079	-9999	-0.28	37	37
TRAF6	0.017	0.033	-9999	-0.32	5	5
RAC1	0.018	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.078	0.18	-9999	-0.36	133	133
CCM2	0.018	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.034	0.11	-9999	-0.31	55	55
MAPK11	0.018	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.04	0.12	-9999	-0.29	87	87
OSM/MEKK3	0.026	0.008	-9999	-10000	0	0
TAOK1	0.012	0.044	-9999	-0.32	7	7
TAOK2	0.02	0.005	-9999	-10000	0	0
TAOK3	0.019	0.016	-9999	-0.32	1	1
MAP3K7IP1	0.018	0	-9999	-10000	0	0
MAPK14	0.017	0.012	-9999	-0.25	1	1
MAP3K7IP2	0.014	0.047	-9999	-0.52	4	4
MAP3K5	-0.022	0.13	-9999	-0.42	47	47
MAP3K10	-0.001	0.097	-9999	-0.48	20	20
MAP3K3	0.017	0.012	-9999	-0.25	1	1
TRX/ASK1	-0.003	0.079	-9999	-0.31	30	30
GADD45/MTK1/MTK1	0.009	0.097	-9999	-0.29	42	42

×

BARD1 signaling events

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
BARD1/CSTF1	0.021	0.042	-10000	0	-0.37	5	5
ATM	0.017	0.012	-10000	0	-0.25	1	1
UBE2D3	0.018	0	-10000	0	-10000	0	0
PRKDC	0.012	0.045	-10000	0	-0.31	9	9
ATR	0.017	0.012	-10000	0	-0.25	1	1
UBE2L3	0.018	0	-10000	0	-10000	0	0
FANCD2	0.029	0.012	-10000	0	-10000	0	0
protein ubiquitination	0.016	0.083	-10000	0	-0.28	26	26
XRCC5	0.018	0	-10000	0	-10000	0	0
XRCC6	0.017	0.012	-10000	0	-0.25	1	1
M/R/N Complex	0.03	0.045	-10000	0	-0.3	9	9
MRE11A	0.018	0	-10000	0	-10000	0	0
DNA-PK	0.032	0.028	-10000	0	-0.3	2	2
FA complex/FANCD2/Ubiquitin	0.028	0.075	-10000	0	-0.35	8	8
FANCF	0.012	0.057	-10000	0	-0.52	6	6
BRCA1	0	0.094	-10000	0	-0.48	19	19
CCNE1	-0.018	0.099	-10000	0	-0.28	64	64
CDK2/Cyclin E1	-0.002	0.08	-10000	0	-0.37	11	11
FANCG	0.016	0.024	-10000	0	-0.25	4	4
BRCA1/BACH1/BARD1	0.01	0.076	-10000	0	-0.37	20	20
FANCE	0.006	0.061	-10000	0	-0.3	19	19
FANCC	0.013	0.042	-10000	0	-0.33	7	7
NBN	0.015	0.035	-10000	0	-0.43	3	3
FANCA	-0.032	0.12	-10000	0	-0.31	80	80
DNA repair	0.012	0.12	-10000	0	-0.38	26	26
BRCA1/BARD1/ubiquitin	0.01	0.076	-10000	0	-0.37	20	20
BARD1/DNA-PK	0.04	0.038	-10000	0	-0.27	6	6
FANCL	0.014	0.031	-10000	0	-0.25	7	7
mRNA polyadenylation	-0.021	0.042	0.37	5	-10000	0	5
BRCA1/BARD1/CTIP/M/R/N Complex	0.026	0.057	-10000	0	-0.32	2	2
BRCA1/BACH1/BARD1/TopBP1	0.022	0.068	-10000	0	-0.31	20	20
BRCA1/BARD1/P53	0.01	0.11	-10000	0	-0.3	51	51
BARD1/CSTF1/BRCA1	0.02	0.069	-10000	0	-0.3	21	21
BRCA1/BACH1	0	0.094	-10000	0	-0.48	19	19
BARD1	0.014	0.047	-10000	0	-0.52	4	4
PCNA	0.009	0.064	-10000	0	-0.39	12	12
BRCA1/BARD1/UbcH5C	0.022	0.066	-10000	0	-0.3	20	20
BRCA1/BARD1/UbcH7	0.022	0.066	-10000	0	-0.3	20	20
BRCA1/BARD1/RAD51/PCNA	-0.006	0.12	-10000	0	-0.28	74	74
BARD1/DNA-PK/P53	0.025	0.085	-10000	0	-0.25	43	43
BRCA1/BARD1/Ubiquitin	0.01	0.076	-10000	0	-0.37	20	20
BRCA1/BARD1/CTIP	0.015	0.081	-10000	0	-0.28	32	32
FA complex	0.017	0.073	-10000	0	-0.25	24	24
BARD1/EWS	0.023	0.034	-10000	0	-0.37	4	4
RBBP8	0.007	0.07	-10000	0	-0.37	12	12
TP53	-0.023	0.14	-10000	0	-0.48	43	43
TOPBP1	0.017	0.017	-10000	0	-0.25	2	2
G1/S transition of mitotic cell cycle	-0.008	0.11	0.3	51	-10000	0	51
BRCA1/BARD1	0.02	0.085	-10000	0	-0.28	26	26
CSTF1	0.014	0.035	-10000	0	-0.3	6	6
BARD1/EWS-Fli1	0.01	0.034	-10000	0	-0.38	4	4
CDK2	0.012	0.047	-10000	0	-0.31	10	10
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.041	0.16	-10000	0	-0.47	64	64
RAD50	0.011	0.062	-10000	0	-0.52	7	7
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.01	0.076	-10000	0	-0.37	20	20
EWSR1	0.018	0	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0.023	-9999	-0.52	1	1
HDAC2	0.009	0.053	-9999	-0.29	15	15
GNB1/GNG2	-0.008	0.11	-9999	-0.31	55	55
forebrain development	0.005	0.14	-9999	-0.58	15	15
GNAO1	0.017	0.024	-9999	-0.25	4	4
SMO/beta Arrestin2	-0.018	0.12	-9999	-0.37	49	49
SMO	-0.047	0.16	-9999	-0.41	82	82
ARRB2	0.019	0.001	-9999	-10000	0	0
GLI3/SPOP	0.011	0.13	-9999	-0.43	21	21
mol:GTP	0.001	0.001	-9999	-10000	0	0
GSK3B	0.018	0	-9999	-10000	0	0
GNAI2	0.007	0.075	-9999	-0.48	12	12
SIN3/HDAC complex	0.041	0.032	-9999	-0.27	5	5
GNAI1	-0.016	0.12	-9999	-0.38	46	46
XPO1	0.021	0.003	-9999	-10000	0	0
GLI1/Su(fu)	-0.006	0.17	-9999	-0.58	25	25
SAP30	0.012	0.053	-9999	-0.48	6	6
mol:GDP	-0.047	0.16	-9999	-0.41	82	82
MIM/GLI2A	-0.022	0.14	-9999	-0.4	61	61
IFT88	-0.001	0.097	-9999	-0.48	20	20
GNAI3	0.019	0.001	-9999	-10000	0	0
GLI2	0.035	0.055	-9999	-0.41	1	1
GLI3	0.004	0.14	-9999	-0.38	30	30
CSNK1D	0.018	0	-9999	-10000	0	0
CSNK1E	0.017	0.012	-9999	-0.25	1	1
SAP18	0.017	0	-9999	-10000	0	0
embryonic digit morphogenesis	-0.001	0.097	-9999	-0.48	20	20
GNG2	0.016	0.029	-9999	-0.34	3	3
Gi family/GTP	-0.008	0.12	-9999	-0.38	25	25
SIN3B	0.017	0.012	-9999	-0.25	1	1
SIN3A	0.017	0	-9999	-10000	0	0
GLI3/Su(fu)	0.009	0.14	-9999	-0.43	35	35
GLI2/Su(fu)	0.026	0.1	-9999	-0.45	6	6
FOXA2	-0.051	0.18	-9999	-0.73	34	34
neural tube patterning	0.005	0.14	-9999	-0.58	15	15
SPOP	0.013	0.042	-9999	-0.33	7	7
Su(fu)/PIAS1	0.004	0.093	-9999	-0.34	21	21
GNB1	0.013	0.052	-9999	-0.52	5	5
CSNK1G2	0.016	0.033	-9999	-0.52	2	2
CSNK1G3	0.013	0.052	-9999	-0.52	5	5
MTSS1	-0.023	0.14	-9999	-0.4	61	61
embryonic limb morphogenesis	0.005	0.14	-9999	-0.58	15	15
SUFU	-0.006	0.1	-9999	-0.38	21	21
LGALS3	-0.041	0.16	-9999	-0.48	63	63
catabolic process	0.031	0.12	-9999	-0.36	24	24
GLI3A/CBP	0.006	0.07	-9999	-0.36	10	10
KIF3A	0.007	0.074	-9999	-0.5	11	11
GLI1	0.005	0.14	-9999	-0.6	15	15
RAB23	0.008	0.065	-9999	-0.38	13	13
CSNK1A1	0.017	0.023	-9999	-0.52	1	1
IFT172	0.013	0.049	-9999	-0.43	6	6
RBBP7	0.01	0.051	-9999	-0.3	13	13
Su(fu)/Galectin3	-0.028	0.14	-9999	-0.34	71	71
GNAZ	0.002	0.088	-9999	-0.44	19	19
RBBP4	0.016	0.026	-9999	-0.39	2	2
CSNK1G1	0.017	0.012	-9999	-0.25	1	1
PIAS1	0.017	0.012	-9999	-0.25	1	1
PRKACA	0.018	0	-9999	-10000	0	0
GLI2/SPOP	0.04	0.057	-9999	-0.39	2	2
STK36	0	0.11	-9999	-0.52	21	21
Gi family/GNB1/GNG2/GDP	0	0.11	-9999	-0.4	20	20
PTCH1	0.014	0.13	-9999	-0.66	7	7
MIM/GLI1	0	0.16	-9999	-0.56	19	19
CREBBP	0.006	0.07	-9999	-0.36	10	10
Su(fu)/SIN3/HDAC complex	0.036	0.047	-9999	-0.26	1	1

×

Signaling events mediated by HDAC Class III

Figure S98. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S98. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.014	0.047	-10000	0	-0.52	4	4
HDAC4	0.017	0.023	-10000	0	-0.52	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.011	0.027	0.24	3	-0.13	10	13
CDKN1A	-0.018	0.13	-10000	0	-0.71	16	16
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.016	0.02	-10000	0	-0.25	3	3
FOXO3	0.001	0.043	0.41	4	-0.25	4	8
FOXO1	0	0.092	-10000	0	-0.46	19	19
FOXO4	0.022	0.034	-10000	0	-0.27	7	7
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.017	0.012	-10000	0	-0.25	1	1
TAT	-0.007	0.078	-10000	0	-0.25	48	48
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.011	0.091	-10000	0	-0.34	36	36
PPARGC1A	-0.012	0.1	-10000	0	-0.31	48	48
FHL2	-0.077	0.19	-10000	0	-0.41	117	117
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.024	0.029	-10000	0	-0.37	1	1
HIST2H4A	0.011	0.027	0.13	10	-0.24	3	13
SIRT1/FOXO3a	0.005	0.041	0.32	4	-0.19	7	11
SIRT1	0.016	0.04	0.2	10	-0.35	3	13
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.034	0.029	-10000	0	-0.31	2	2
SIRT1/Histone H1b	0.004	0.072	-10000	0	-0.23	38	38
apoptosis	-0.033	0.028	0.31	1	-10000	0	1
SIRT1/PGC1A	0.005	0.064	-10000	0	-0.32	11	11
p53/SIRT1	-0.016	0.11	0.4	10	-0.37	32	42
SIRT1/FOXO4	0.027	0.038	-10000	0	-0.24	7	7
FOXO1/FHL2/SIRT1	-0.03	0.12	-10000	0	-0.3	79	79
HIST1H1E	-0.005	0.08	-10000	0	-0.27	39	39
SIRT1/p300	0.022	0.043	-10000	0	-0.36	5	5
muscle cell differentiation	0.002	0.081	0.31	30	-10000	0	30
TP53	-0.022	0.14	-10000	0	-0.47	43	43
KU70/SIRT1/BAX	0.033	0.028	-10000	0	-0.31	1	1
CREBBP	0.016	0.033	-10000	0	-0.52	2	2
MEF2D	0.018	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.008	0.06	-10000	0	-0.37	1	1
ACSS2	0.023	0.029	-10000	0	-0.37	1	1
SIRT1/PCAF/MYOD	-0.002	0.081	-10000	0	-0.32	30	30

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.019	0.052	-9999	-0.37	9	9
FBXW11	0.015	0.035	-9999	-0.43	3	3
NF kappa B1 p50/c-Rel	0.018	0.062	-9999	-0.31	15	15
NF kappa B1 p50/RelA/I kappa B alpha	0	0.11	-9999	-0.44	18	18
NFKBIA	-0.024	0.12	-9999	-0.26	87	87
MAPK14	0.017	0.012	-9999	-0.25	1	1
NF kappa B1 p105/p50	0.026	0.038	-9999	-0.3	5	5
ARRB2	0.02	0.005	-9999	-10000	0	0
REL	0.001	0.087	-9999	-0.41	21	21
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.022	0.054	-9999	-0.3	12	12
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.028	0.031	-9999	-0.3	3	3
PIK3CA	0.016	0.029	-9999	-0.34	3	3
NF kappa B1 p50 dimer	0.019	0.037	-9999	-0.37	3	3
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
NFKB1	0.02	0.037	-9999	-0.37	3	3
RELA	0.018	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	-0.014	0.1	-9999	-0.4	16	16
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.005	0.11	-9999	-0.44	17	17
SRC	0.015	0.035	-9999	-0.43	3	3
PI3K	0.005	0.082	-9999	-0.37	21	21
NF kappa B1 p50/RelA	-0.014	0.1	-9999	-0.4	16	16
IKBKB	0.012	0.047	-9999	-0.31	10	10
beta TrCP1/SCF ubiquitin ligase complex	0.015	0.035	-9999	-0.43	3	3
SYK	-0.023	0.14	-9999	-0.48	43	43
I kappa B alpha/PIK3R1	-0.027	0.13	-9999	-0.37	39	39
cell death	0.005	0.1	-9999	-0.42	17	17
NF kappa B1 p105/c-Rel	0.018	0.062	-9999	-0.31	15	15
LCK	-0.074	0.18	-9999	-0.4	117	117
BCL3	0.008	0.071	-9999	-0.5	10	10

×

Regulation of p38-alpha and p38-beta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.023	0.016	-9999	-0.31	1	1
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.017	0.023	-9999	-0.52	1	1
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.011	0.11	-9999	-0.4	37	37
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	-0.006	0.1	-9999	-0.38	31	31
RAC1-CDC42/GTP/PAK family	-0.001	0.072	-9999	-0.22	41	41
response to UV	0	0	-9999	-10000	0	0
YES1	0.007	0.07	-9999	-0.43	12	12
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.017	0.012	-9999	-0.25	1	1
FYN	0.008	0.067	-9999	-0.41	12	12
MAP3K12	0.018	0	-9999	-10000	0	0
FGR	0.017	0.017	-9999	-0.25	2	2
p38 alpha/TAB1	0.01	0.094	-9999	-0.28	29	29
PRKG1	0.017	0.012	-9999	-0.25	1	1
DUSP8	-0.005	0.1	-9999	-0.48	24	24
PGK/cGMP/p38 alpha	-0.028	0.071	-9999	-0.27	29	29
apoptosis	0.009	0.09	-9999	-0.27	29	29
RAL/GTP	0.022	0.029	-9999	-0.31	4	4
LYN	0.014	0.031	-9999	-0.25	7	7
DUSP1	-0.038	0.15	-9999	-0.41	69	69
PAK1	-0.022	0.13	-9999	-0.37	54	54
SRC	0.015	0.035	-9999	-0.43	3	3
RAC1/OSM/MEKK3/MKK3	0.043	0.021	-9999	-0.27	1	1
TRAF6	0.017	0.023	-9999	-0.52	1	1
RAC1	0.018	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.018	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.024	0	-9999	-10000	0	0
MAPK11	0.002	0.11	-9999	-0.32	34	34
BLK	-0.019	0.1	-9999	-0.29	63	63
HCK	-0.005	0.11	-9999	-0.47	25	25
MAP2K3	0.014	0.037	-9999	-0.29	7	7
DUSP16	0.005	0.078	-9999	-0.43	15	15
DUSP10	-0.017	0.12	-9999	-0.39	44	44
TRAF6/MEKK3	0.022	0.015	-9999	-0.28	1	1
MAP3K7IP1	0.018	0	-9999	-10000	0	0
MAPK14	0.003	0.1	-9999	-0.3	33	33
positive regulation of innate immune response	0.002	0.12	-9999	-0.37	31	31
LCK	-0.074	0.18	-9999	-0.4	117	117
p38alpha-beta/MKP7	0.006	0.13	-9999	-0.36	36	36
p38alpha-beta/MKP5	-0.003	0.13	-9999	-0.35	39	39
PGK/cGMP	0.013	0.008	-9999	-0.17	1	1
PAK2	0.018	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.013	0.14	-9999	-0.36	45	45
CDC42	0.018	0	-9999	-10000	0	0
RALB	0.014	0.047	-9999	-0.52	4	4
RALA	0.018	0	-9999	-10000	0	0
PAK3	-0.033	0.13	-9999	-0.32	80	80

×

Signaling events mediated by PRL

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
CCNE1	-0.018	0.099	-10000	0	-0.28	64	64
mol:Halofuginone	0.004	0.012	-10000	0	-0.16	1	1
ITGA1	0	0.096	-10000	0	-0.51	18	18
CDKN1A	-0.017	0.12	-10000	0	-0.47	24	24
PRL-3/alpha Tubulin	0.024	0.026	-10000	0	-0.37	1	1
mol:Ca2+	-0.076	0.13	0.38	1	-0.38	63	64
AGT	-0.095	0.19	-10000	0	-0.36	158	158
CCNA2	-0.044	0.13	-10000	0	-0.42	19	19
TUBA1B	0.018	0	-10000	0	-10000	0	0
EGR1	-0.06	0.15	-10000	0	-0.37	82	82
CDK2/Cyclin E1	-0.016	0.12	-10000	0	-0.43	29	29
MAPK3	0.022	0.032	-10000	0	-0.37	2	2
PRL-2 /Rab GGTase beta	0.017	0.053	-10000	0	-0.37	8	8
MAPK1	0.021	0.035	-10000	0	-0.37	3	3
PTP4A1	-0.031	0.12	-10000	0	-0.59	5	5
PTP4A3	0.014	0.037	-10000	0	-0.29	7	7
PTP4A2	0.006	0.072	-10000	0	-0.4	15	15
ITGB1	0.02	0.041	-10000	0	-0.23	12	12
SRC	0.015	0.035	-10000	0	-0.43	3	3
RAC1	0.004	0.066	-10000	0	-0.57	2	2
Rab GGTase beta/Rab GGTase alpha	0.026	0.011	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.022	0.12	-10000	0	-0.56	5	5
RABGGTA	0.018	0	-10000	0	-10000	0	0
BCAR1	0.002	0.023	0.38	1	-0.18	1	2
RHOC	0.001	0.075	-10000	0	-0.5	5	5
RHOA	-0.006	0.089	-10000	0	-0.42	14	14
cell motility	0.002	0.075	-10000	0	-0.36	6	6
PRL-1/alpha Tubulin	-0.02	0.12	-10000	0	-0.61	4	4
PRL-3/alpha1 Integrin	0.011	0.077	-10000	0	-0.39	17	17
ROCK1	0.002	0.075	-10000	0	-0.36	6	6
RABGGTB	0.017	0.017	-10000	0	-0.25	2	2
CDK2	0.012	0.047	-10000	0	-0.31	10	10
mitosis	-0.031	0.12	-10000	0	-0.59	5	5
ATF5	0.013	0.04	-10000	0	-0.28	9	9

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.017	0.023	-10000	0	-0.52	1	1
HDAC3	0.018	0	-10000	0	-10000	0	0
VDR	-0.003	0.1	-10000	0	-0.51	21	21
Cbp/p300/PCAF	0.02	0.036	-10000	0	-0.31	6	6
EP300	0.014	0.047	-10000	0	-0.52	4	4
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.022	0.059	-10000	0	-0.28	3	3
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.017	0.012	-10000	0	-0.25	1	1
AKT1	0.03	0.093	0.22	53	-0.25	19	72
RAR alpha/9cRA/Cyclin H	-0.024	0.062	-10000	0	-0.4	5	5
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.014	0.07	-10000	0	-0.29	9	9
CDC2	-0.012	0.12	-10000	0	-0.44	34	34
response to UV	-0.002	0.009	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.015	0.049	-10000	0	-0.37	5	5
NCOR2	0.018	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.075	-10000	0	-0.37	21	21
RXRs/RARs/NRIP1/9cRA	-0.009	0.19	-10000	0	-0.54	54	54
NCOA2	0.009	0.063	-10000	0	-0.4	11	11
NCOA3	0.013	0.047	-10000	0	-0.37	7	7
NCOA1	0.012	0.057	-10000	0	-0.52	6	6
VDR/VDR/DNA	-0.003	0.1	-10000	0	-0.51	21	21
RARG	0.016	0.024	-10000	0	-0.52	1	1
RAR gamma1/9cRA	0.022	0.016	-10000	0	-0.31	1	1
MAPK3	0.015	0.027	-10000	0	-0.39	2	2
MAPK1	0.016	0.033	-10000	0	-0.52	2	2
MAPK8	0.013	0.041	-10000	0	-0.52	3	3
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.002	0.12	-10000	0	-0.45	11	11
RARA	0.019	0.047	-10000	0	-0.25	8	8
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.014	0.067	-10000	0	-0.26	7	7
PRKCA	0.011	0.038	-10000	0	-0.26	8	8
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.026	0.21	-10000	0	-0.6	54	54
RXRG	0.014	0.063	-10000	0	-0.33	12	12
RXRA	0.011	0.08	-10000	0	-0.29	8	8
RXRB	0.021	0.041	-10000	0	-0.3	3	3
VDR/Vit D3/DNA	-0.002	0.075	-10000	0	-0.37	21	21
RBP1	-0.076	0.19	-10000	0	-0.42	112	112
CRBP1/9-cic-RA	-0.053	0.14	-10000	0	-0.3	112	112
RARB	-0.025	0.13	-10000	0	-0.36	60	60
PRKCG	0.016	0.017	-10000	0	-10000	0	0
MNAT1	0.017	0.012	-10000	0	-0.25	1	1
RAR alpha/RXRs	0.02	0.15	-10000	0	-0.42	19	19
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.023	0.11	-10000	0	-0.33	14	14
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.064	-10000	0	-0.27	4	4
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.026	0.21	-10000	0	-0.6	54	54
positive regulation of DNA binding	-0.023	0.059	-10000	0	-0.38	5	5
NRIP1	-0.085	0.38	-10000	0	-1.2	53	53
RXRs/RARs	-0.011	0.15	-10000	0	-0.42	55	55
RXRs/RXRs/DNA/9cRA	0.003	0.12	-10000	0	-0.31	51	51
PRKACA	0.018	0	-10000	0	-10000	0	0
CDK7	0.017	0.012	-10000	0	-0.25	1	1
TFIIH	0.033	0.031	-10000	0	-0.3	4	4
RAR alpha/9cRA	0.04	0.041	-10000	0	-0.27	3	3
CCNH	0.014	0.047	-10000	0	-0.52	4	4
CREBBP	0.016	0.033	-10000	0	-0.52	2	2
RAR gamma2/9cRA	-0.002	0.022	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.002	0.14	-9999	-1.1	5	5
MKNK1	0.018	0	-9999	-10000	0	0
MAPK14	0.006	0.055	-9999	-0.29	6	6
ATF2/c-Jun	-0.028	0.19	-9999	-0.6	49	49
MAPK11	0.006	0.053	-9999	-0.28	5	5
MITF	0.014	0.071	-9999	-0.34	11	11
MAPKAPK5	0.018	0.059	-9999	-0.33	5	5
KRT8	-0.004	0.1	-9999	-0.34	31	31
MAPKAPK3	0.017	0.017	-9999	-0.25	2	2
MAPKAPK2	0.014	0.047	-9999	-0.52	4	4
p38alpha-beta/CK2	0.009	0.074	-9999	-0.39	6	6
CEBPB	0.011	0.072	-9999	-0.32	11	11
SLC9A1	0.018	0.059	-9999	-0.33	5	5
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.013	0.079	-9999	-0.31	6	6
p38alpha-beta/MNK1	0.023	0.059	-9999	-0.32	5	5
JUN	-0.028	0.19	-9999	-0.6	49	49
PPARGC1A	0.003	0.088	-9999	-0.35	15	15
USF1	0.006	0.084	-9999	-0.36	14	14
RAB5/GDP/GDI1	0.019	0.042	-9999	-0.23	5	5
NOS2	0.008	0.059	-9999	-0.34	5	5
DDIT3	0.014	0.066	-9999	-0.37	6	6
RAB5A	0.018	0	-9999	-10000	0	0
HSPB1	-0.012	0.12	-9999	-0.33	54	54
p38alpha-beta/HBP1	0.021	0.066	-9999	-0.34	8	8
CREB1	0.014	0.075	-9999	-0.29	14	14
RAB5/GDP	0.013	0	-9999	-10000	0	0
EIF4E	0.025	0.049	-9999	-0.27	5	5
RPS6KA4	0.018	0.061	-9999	-0.32	6	6
PLA2G4A	-0.006	0.1	-9999	-0.31	30	30
GDI1	0.017	0.061	-9999	-0.32	6	6
TP53	-0.001	0.096	-9999	-0.35	20	20
RPS6KA5	0	0.1	-9999	-0.34	33	33
ESR1	-0.09	0.17	-9999	-0.33	155	155
HBP1	0.015	0.04	-9999	-0.52	3	3
MEF2C	-0.001	0.1	-9999	-0.34	32	32
MEF2A	0.017	0.062	-9999	-0.33	6	6
EIF4EBP1	0.008	0.08	-9999	-0.3	14	14
KRT19	-0.014	0.12	-9999	-0.34	53	53
ELK4	0.016	0.065	-9999	-0.31	9	9
ATF6	0.018	0.06	-9999	-0.32	6	6
ATF1	0.014	0.076	-9999	-0.29	14	14
p38alpha-beta/MAPKAPK2	0.02	0.069	-9999	-0.37	8	8
p38alpha-beta/MAPKAPK3	0.022	0.059	-9999	-0.32	5	5

×

Signaling events mediated by VEGFR1 and VEGFR2

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.001	0.094	-9999	-0.4	22	22
AKT1	0.029	0.15	-9999	-0.5	22	22
PTK2B	0.015	0.13	-9999	-0.56	15	15
VEGFR2 homodimer/Frs2	0.02	0.098	-9999	-0.56	10	10
CAV1	-0.001	0.083	-9999	-0.33	29	29
CALM1	0.018	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.019	0.11	-9999	-0.55	11	11
endothelial cell proliferation	0.046	0.13	-9999	-0.47	17	17
mol:Ca2+	0.014	0.14	-9999	-0.57	17	17
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.033	0.1	-9999	-0.54	10	10
RP11-342D11.1	0.005	0.14	-9999	-0.58	16	16
CDH5	0.013	0.052	-9999	-0.52	5	5
VEGFA homodimer	0.003	0.099	-9999	-0.27	52	52
SHC1	0.017	0.023	-9999	-0.52	1	1
SHC2	-0.06	0.19	-9999	-0.51	77	77
HRAS/GDP	-0.036	0.099	-9999	-0.51	15	15
SH2D2A	-0.039	0.15	-9999	-0.38	76	76
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.044	0.12	-9999	-0.46	16	16
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.008	0.14	-9999	-0.56	14	14
VEGFR1 homodimer	0.004	0.08	-9999	-0.45	15	15
SHC/GRB2/SOS1	0.026	0.13	-9999	-0.56	15	15
GRB10	0.005	0.17	-9999	-0.61	28	28
PTPN11	0.017	0.023	-9999	-0.52	1	1
GRB2	0.016	0.024	-9999	-0.25	4	4
PAK1	-0.022	0.13	-9999	-0.37	54	54
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.029	0.12	-9999	-0.52	15	15
HRAS	0.012	0.051	-9999	-0.41	7	7
VEGF/Rho/ROCK1/Integrin Complex	0.018	0.12	-9999	-0.56	13	13
HIF1A	-0.037	0.16	-9999	-0.46	61	61
FRS2	0.011	0.047	-9999	-0.27	13	13
oxygen and reactive oxygen species metabolic process	0.031	0.1	-9999	-0.53	10	10
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.018	0	-9999	-10000	0	0
Nck/Pak	-0.007	0.095	-9999	-0.37	25	25
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.018	0.12	-9999	-0.63	11	11
mol:GDP	-0.038	0.1	-9999	-0.53	16	16
mol:NADP	0.042	0.11	-9999	-0.4	17	17
eNOS/Hsp90	0.047	0.11	-9999	-0.38	16	16
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
mol:IP3	0.014	0.14	-9999	-0.58	17	17
HIF1A/ARNT	-0.014	0.12	-9999	-0.37	47	47
SHB	0.008	0.067	-9999	-0.41	12	12
VEGFA	-0.002	0.076	-9999	-0.28	31	31
VEGFC	-0.001	0.095	-9999	-0.47	20	20
FAK1/Vinculin	0.034	0.13	-9999	-0.61	12	12
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.005	0.08	-9999	-0.52	12	12
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.015	0.14	-9999	-0.6	15	15
PTPN6	0.015	0.035	-9999	-0.43	3	3
EPAS1	0.012	0.088	-9999	-0.44	18	18
mol:L-citrulline	0.042	0.11	-9999	-0.4	17	17
ITGAV	-0.002	0.1	-9999	-0.48	21	21
PIK3CA	0.016	0.029	-9999	-0.34	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.028	0.11	-9999	-0.52	11	11
VEGFR2 homodimer/VEGFA homodimer	0.013	0.15	-9999	-0.64	16	16
VEGFR2/3 heterodimer	0.024	0.095	-9999	-0.56	10	10
VEGFB	0.017	0.023	-9999	-0.52	1	1
MAPK11	0.015	0.14	-9999	-0.59	17	17
VEGFR2 homodimer	0.018	0.11	-9999	-0.55	15	15
FLT1	0.004	0.08	-9999	-0.45	15	15
NEDD4	0.001	0.093	-9999	-0.53	15	15
MAPK3	0.017	0.13	-9999	-0.52	17	17
MAPK1	0.016	0.13	-9999	-0.52	17	17
VEGFA145/NRP2	0.009	0.065	-9999	-0.37	8	8
VEGFR1/2 heterodimer	0.016	0.11	-9999	-0.59	12	12
KDR	0.018	0.11	-9999	-0.55	15	15
VEGFA165/NRP1/VEGFR2 homodimer	0.017	0.14	-9999	-0.59	17	17
SRC	0.015	0.035	-9999	-0.43	3	3
platelet activating factor biosynthetic process	0.018	0.13	-9999	-0.54	17	17
PI3K	0.02	0.16	-9999	-0.58	22	22
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.02	0.11	-9999	-0.57	10	10
FES	0.011	0.15	-9999	-0.62	16	16
GAB1	0.02	0.15	-9999	-0.58	17	17
VEGFR2 homodimer/VEGFA homodimer/Src	0.022	0.11	-9999	-0.57	10	10
CTNNB1	0.001	0.09	-9999	-0.45	19	19
SOS1	0.017	0.023	-9999	-0.52	1	1
ARNT	0.018	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.041	0.12	-9999	-0.42	18	18
VEGFR2 homodimer/VEGFA homodimer/Yes	0.018	0.12	-9999	-0.54	13	13
PI3K/GAB1	0.027	0.16	-9999	-0.49	23	23
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.013	0.12	-9999	-0.44	18	18
PRKACA	0.018	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.024	0.12	-9999	-0.54	15	15
HSP90AA1	0.013	0.045	-9999	-0.39	6	6
CDC42	0.015	0.14	-9999	-0.6	16	16
actin cytoskeleton reorganization	-0.008	0.13	-9999	-0.55	14	14
PTK2	0.026	0.14	-9999	-0.66	12	12
EDG1	-0.003	0.19	-9999	-0.64	31	31
mol:DAG	0.014	0.14	-9999	-0.58	17	17
CaM/Ca2+	0.021	0.13	-9999	-0.53	17	17
MAP2K3	0.015	0.14	-9999	-0.55	19	19
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.011	0.18	-9999	-0.62	28	28
PLCG1	0.014	0.14	-9999	-0.59	17	17
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.027	0.11	-9999	-0.5	13	13
IQGAP1	0.018	0	-9999	-10000	0	0
YES1	0.007	0.07	-9999	-0.43	12	12
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.023	0.11	-9999	-0.57	11	11
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.022	0.11	-9999	-0.57	10	10
cell migration	0.055	0.12	-9999	-0.64	8	8
mol:PI-3-4-5-P3	0.021	0.15	-9999	-0.54	22	22
FYN	0.008	0.067	-9999	-0.41	12	12
VEGFB/NRP1	0.014	0.13	-9999	-0.56	16	16
mol:NO	0.042	0.11	-9999	-0.4	17	17
PXN	0.018	0	-9999	-10000	0	0
HRAS/GTP	-0.036	0.098	-9999	-0.51	15	15
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.009	0.17	-9999	-0.62	28	28
VHL	0.015	0.029	-9999	-0.25	6	6
ITGB3	0.002	0.075	-9999	-0.32	25	25
NOS3	0.041	0.12	-9999	-0.45	17	17
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.021	0.15	-9999	-0.49	24	24
RAC1	0.018	0	-9999	-10000	0	0
PRKCA	0.019	0.13	-9999	-0.54	17	17
PRKCB	0.012	0.13	-9999	-0.54	17	17
VCL	0.016	0.029	-9999	-0.34	3	3
VEGFA165/NRP1	0.008	0.14	-9999	-0.59	16	16
VEGFR1/2 heterodimer/VEGFA homodimer	0.016	0.12	-9999	-0.59	13	13
VEGFA165/NRP2	0.009	0.065	-9999	-0.37	8	8
MAPKKK cascade	0.031	0.15	-9999	-0.51	28	28
NRP2	0.011	0.052	-9999	-0.33	11	11
VEGFC homodimer	-0.001	0.095	-9999	-0.47	20	20
NCK1	0.011	0.045	-9999	-0.28	12	12
ROCK1	0.018	0	-9999	-10000	0	0
FAK1/Paxillin	0.035	0.13	-9999	-0.6	12	12
MAP3K13	0.01	0.15	-9999	-0.58	19	19
PDPK1	0.027	0.14	-9999	-0.47	23	23

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.01	0.066	-9999	-0.52	8	8
mol:S1P	0	0.005	-9999	-0.015	43	43
S1P1/S1P/Gi	0	0.1	-9999	-0.4	16	16
GNAO1	0.016	0.024	-9999	-0.25	4	4
S1P/S1P3/G12/G13	0.02	0.031	-9999	-0.29	4	4
AKT1	0.012	0.097	-9999	-0.58	12	12
AKT3	0.004	0.14	-9999	-1.2	4	4
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.01	0.066	-9999	-0.52	8	8
GNAI2	0.007	0.075	-9999	-0.48	12	12
GNAI3	0.018	0.004	-9999	-10000	0	0
GNAI1	-0.016	0.12	-9999	-0.38	46	46
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.001	0.005	-9999	-0.017	43	43
S1PR2	0	0	-9999	-10000	0	0
EDG1	-0.019	0.12	-9999	-0.4	46	46
mol:Ca2+	0.01	0.081	-9999	-0.36	8	8
MAPK3	0.016	0.078	-9999	-0.36	7	7
MAPK1	0.016	0.078	-9999	-0.36	7	7
JAK2	0.006	0.095	-9999	-0.35	17	17
CXCR4	-0.006	0.11	-9999	-0.41	18	18
FLT1	0.006	0.08	-9999	-0.45	15	15
RhoA/GDP	0.004	0.058	-9999	-0.38	12	12
Rac1/GDP	0.013	0	-9999	-10000	0	0
SRC	0.015	0.08	-9999	-0.36	9	9
S1P/S1P3/Gi	0.01	0.082	-9999	-0.36	8	8
RAC1	0.018	0	-9999	-10000	0	0
RhoA/GTP	0.011	0.087	-9999	-0.38	9	9
VEGFA	0.001	0.076	-9999	-0.29	31	31
S1P/S1P2/Gi	0.009	0.076	-9999	-0.29	14	14
VEGFR1 homodimer/VEGFA homodimer	0.01	0.083	-9999	-0.34	19	19
RHOA	0.005	0.08	-9999	-0.52	12	12
S1P/S1P3/Gq	-0.027	0.094	-9999	-0.27	58	58
GNAQ	0	0	-9999	-10000	0	0
GNAZ	0.002	0.088	-9999	-0.44	19	19
G12/G13	0.021	0.039	-9999	-0.37	4	4
GNA14	-0.079	0.18	-9999	-0.35	140	140
GNA15	0.002	0.076	-9999	-0.34	23	23
GNA12	0.018	0	-9999	-10000	0	0
GNA13	0.011	0.055	-9999	-0.36	10	10
GNA11	0.014	0.047	-9999	-0.52	4	4
Rac1/GTP	0.018	0.075	-9999	-0.34	7	7

×

Neurotrophic factor-mediated Trk receptor 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
CRKL	0.014	0.047	-10000	0	-0.52	4	4
RAS family/GTP/Tiam1	0.003	0.08	-10000	0	-0.37	12	12
NT3 (dimer)/TRKC	-0.019	0.093	-10000	0	-0.35	17	17
NT3 (dimer)/TRKB	-0.015	0.1	-10000	0	-0.32	37	37
SHC/Grb2/SOS1/GAB1/PI3K	0.023	0.065	-10000	0	-10000	0	0
RAPGEF1	0.018	0	-10000	0	-10000	0	0
BDNF	-0.016	0.091	-10000	0	-0.26	64	64
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
DYNLT1	0.018	0	-10000	0	-10000	0	0
NTRK1	0.01	0.053	-10000	0	-0.32	12	12
NTRK2	-0.017	0.11	-10000	0	-0.34	52	52
NTRK3	-0.009	0.081	-10000	0	-0.25	53	53
NT-4/5 (dimer)/TRKB	-0.004	0.079	-10000	0	-0.31	23	23
neuron apoptosis	0.036	0.15	0.34	79	-10000	0	79
SHC 2-3/Grb2	-0.039	0.16	-10000	0	-0.38	77	77
SHC1	0.017	0.023	-10000	0	-0.52	1	1
SHC2	-0.061	0.2	-10000	0	-0.5	78	78
SHC3	-0.007	0.11	-10000	0	-0.47	17	17
STAT3 (dimer)	-0.045	0.14	-10000	0	-0.34	89	89
NT3 (dimer)/TRKA	0.001	0.083	-10000	0	-0.33	17	17
RIN/GDP	0.047	0.05	-10000	0	-0.31	1	1
GIPC1	0.014	0.042	-10000	0	-0.45	4	4
KRAS	0.009	0.065	-10000	0	-0.44	10	10
DNAJA3	0.017	0.066	0.23	20	-0.26	6	26
RIN/GTP	0.011	0.025	-10000	0	-0.31	3	3
CCND1	-0.12	0.29	-10000	0	-0.75	89	89
MAGED1	-0.008	0.11	-10000	0	-0.48	27	27
PTPN11	0.017	0.023	-10000	0	-0.52	1	1
RICS	0.003	0.083	-10000	0	-0.45	16	16
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.034	0.025	-10000	0	-0.3	2	2
GRB2	0.016	0.024	-10000	0	-0.25	4	4
NGF (dimer)/TRKA/MATK	0.008	0.054	-10000	0	-0.3	7	7
TRKA/NEDD4-2	-0.01	0.11	-10000	0	-0.37	39	39
ELMO1	0.017	0.017	-10000	0	-0.25	2	2
RhoG/GTP/ELMO1/DOCK1	0.016	0.049	-10000	0	-0.31	11	11
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.012	0.051	-10000	0	-0.41	7	7
DOCK1	0.006	0.078	-10000	0	-0.5	12	12
GAB2	0.009	0.048	-10000	0	-0.25	17	17
RIT2	0.015	0.035	-10000	0	-0.43	3	3
RIT1	0.016	0.033	-10000	0	-0.52	2	2
FRS2	0.011	0.047	-10000	0	-0.27	13	13
DNM1	0.013	0.047	-10000	0	-0.37	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.016	0.033	-10000	0	-0.52	2	2
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.018	0.064	0.22	21	-0.25	6	27
mol:GDP	0.053	0.065	-10000	0	-0.4	2	2
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.012	0.011	-10000	0	-0.17	2	2
RIT1/GDP	0.048	0.049	-10000	0	-0.31	1	1
TIAM1	0.006	0.073	-10000	0	-0.44	13	13
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
BDNF (dimer)/TRKB	-0.007	0.09	-10000	0	-0.32	24	24
KIDINS220/CRKL/C3G	0.023	0.034	-10000	0	-0.37	4	4
SHC/RasGAP	0.016	0.059	-10000	0	-0.37	11	11
FRS2 family/SHP2	0.031	0.032	-10000	0	-0.3	2	2
SHC/GRB2/SOS1/GAB1	0.037	0.049	-10000	0	-0.26	12	12
RIT1/GTP	0.012	0.024	-10000	0	-0.38	2	2
NT3 (dimer)	-0.021	0.11	-10000	0	-0.28	68	68
RAP1/GDP	-0.006	0.028	-10000	0	-0.26	2	2
KIDINS220/CRKL	0.014	0.047	-10000	0	-0.52	4	4
BDNF (dimer)	-0.016	0.09	-10000	0	-0.26	64	64
ubiquitin-dependent protein catabolic process	-0.007	0.091	-10000	0	-0.31	39	39
Schwann cell development	-0.008	0.017	-10000	0	-10000	0	0
EHD4	0.013	0.052	-10000	0	-0.52	5	5
FRS2 family/GRB2/SOS1	0.04	0.037	-10000	0	-0.39	2	2
FRS2 family/SHP2/CRK family/C3G/GAB2	0.038	0.037	-10000	0	-0.23	6	6
RAP1B	0.013	0.044	-10000	0	-0.32	8	8
RAP1A	0.012	0.057	-10000	0	-0.52	6	6
CDC42/GTP	-0.043	0.077	-10000	0	-0.35	14	14
ABL1	0.018	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.024	0.023	-10000	0	-0.37	1	1
Rap1/GTP	0.032	0.072	-10000	0	-0.41	7	7
STAT3	-0.045	0.14	-10000	0	-0.34	89	89
axon guidance	-0.041	0.074	-10000	0	-0.34	14	14
MAPK3	0.013	0.05	-10000	0	-0.26	8	8
MAPK1	0.013	0.052	-10000	0	-0.27	9	9
CDC42/GDP	0.048	0.048	-10000	0	-0.26	2	2
NTF3	-0.021	0.11	-10000	0	-0.28	68	68
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.018	0.036	-10000	0	-0.31	4	4
PI3K	0.005	0.082	-10000	0	-0.37	21	21
FRS3	0.017	0.012	-10000	0	-0.25	1	1
FAIM	0.016	0.029	-10000	0	-0.34	3	3
GAB1	0.006	0.074	-10000	0	-0.43	14	14
RASGRF1	0.007	0.076	0.23	20	-0.27	11	31
SOS1	0.017	0.023	-10000	0	-0.52	1	1
MCF2L	-0.009	0.083	-10000	0	-0.3	21	21
RGS19	0.014	0.039	-10000	0	-0.36	5	5
CDC42	0.018	0	-10000	0	-10000	0	0
RAS family/GTP	0.047	0.07	-10000	0	-0.38	7	7
Rac1/GDP	0.048	0.048	-10000	0	-0.26	2	2
NGF (dimer)/TRKA/GRIT	0.011	0.06	-10000	0	-0.31	15	15
neuron projection morphogenesis	-0.013	0.13	-10000	0	-0.65	6	6
NGF (dimer)/TRKA/NEDD4-2	-0.007	0.091	-10000	0	-0.31	39	39
MAP2K1	0.034	0.045	-10000	0	-0.24	11	11
NGFR	0.004	0.065	-10000	0	-0.29	23	23
NGF (dimer)/TRKA/GIPC/GAIP	0.028	0.047	-10000	0	-0.27	10	10
RAS family/GTP/PI3K	0.011	0.077	-10000	0	-0.25	39	39
FRS2 family/SHP2/GRB2/SOS1	0.047	0.037	-10000	0	-0.38	2	2
NRAS	0.005	0.076	-10000	0	-0.4	16	16
GRB2/SOS1	0.024	0.023	-10000	0	-0.37	1	1
PRKCI	0.002	0.085	-10000	0	-0.43	18	18
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.018	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.018	0.052	-10000	0	-0.48	4	4
RASA1	0.004	0.078	-10000	0	-0.42	16	16
TRKA/c-Abl	0.021	0.038	-10000	0	-0.37	3	3
SQSTM1	0.012	0.053	-10000	0	-0.48	6	6
BDNF (dimer)/TRKB/GIPC	0.007	0.081	-10000	0	-0.28	22	22
NGF (dimer)/TRKA/p62/Atypical PKCs	0.017	0.059	-10000	0	-0.26	20	20
MATK	-0.003	0.075	-10000	0	-0.27	38	38
NEDD4L	-0.025	0.14	-10000	0	-0.45	48	48
RAS family/GDP	-0.01	0.033	-10000	0	-0.28	1	1
NGF (dimer)/TRKA	0.009	0.07	0.24	21	-0.28	6	27
Rac1/GTP	-0.02	0.052	-10000	0	-0.23	18	18
FRS2 family/SHP2/CRK family	0.045	0.043	-10000	0	-0.26	8	8

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.017	0.079	-9999	-0.37	18	18
CRKL	0.014	0.047	-9999	-0.52	4	4
Rac1/GDP	0.013	0	-9999	-10000	0	0
DOCK1	0.006	0.078	-9999	-0.5	12	12
ITGA4	-0.007	0.1	-9999	-0.39	32	32
alpha4/beta7 Integrin/MAdCAM1	0.023	0.079	-9999	-0.29	27	27
EPO	-0.023	0.097	-9999	-0.25	80	80
alpha4/beta7 Integrin	0.009	0.074	-9999	-0.37	16	16
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0.033	-9999	-0.52	2	2
alpha4/beta1 Integrin	0.006	0.084	-9999	-0.41	17	17
EPO/EPOR (dimer)	-0.003	0.069	-9999	-0.32	2	2
lamellipodium assembly	0.022	0.069	-9999	-0.35	6	6
PIK3CA	0.016	0.029	-9999	-0.34	3	3
PI3K	0.005	0.082	-9999	-0.37	21	21
ARF6	0.016	0.033	-9999	-0.52	2	2
JAK2	0.007	0.079	-9999	-0.32	19	19
PXN	0.018	0	-9999	-10000	0	0
PIK3R1	-0.009	0.11	-9999	-0.42	33	33
MADCAM1	0.014	0.033	-9999	-0.25	8	8
cell adhesion	0.021	0.079	-9999	-0.29	27	27
CRKL/CBL	0.023	0.035	-9999	-0.37	4	4
ITGB1	0.014	0.044	-9999	-0.41	5	5
SRC	-0.001	0.11	-9999	-0.31	48	48
ITGB7	0.018	0	-9999	-10000	0	0
RAC1	0.018	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.005	0.12	-9999	-0.35	46	46
p130Cas/Crk/Dock1	0.018	0.1	-9999	-0.46	8	8
VCAM1	-0.022	0.13	-9999	-0.42	48	48
RHOA	0.005	0.08	-9999	-0.52	12	12
alpha4/beta1 Integrin/Paxillin/GIT1	0.028	0.07	-9999	-0.3	18	18
BCAR1	0.006	0.1	-9999	-0.29	42	42
EPOR	0.016	0.02	-9999	-0.25	3	3
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.017	0.012	-9999	-0.25	1	1
GIT1	0.014	0.035	-9999	-0.3	6	6
Rac1/GTP	0.022	0.071	-9999	-0.36	6	6

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.018	0	-10000	0	-10000	0	0
NFATC1	0.033	0.073	-10000	0	-0.26	24	24
NFATC2	0.027	0.041	-10000	0	-0.25	1	1
NFATC3	0.017	0.006	-10000	0	-10000	0	0
YWHAE	0.016	0.029	-10000	0	-0.34	3	3
Calcineurin A alpha-beta B1/CABIN1	0.003	0.094	-10000	0	-0.38	13	13
Exportin 1/Ran/NUP214	0.035	0.018	-10000	0	-0.3	1	1
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.021	0.09	-10000	0	-0.42	9	9
BCL2/BAX	-0.071	0.16	-10000	0	-0.37	115	115
CaM/Ca2+/Calcineurin A alpha-beta B1	0.015	0.003	-10000	0	-10000	0	0
CaM/Ca2+	0.015	0.003	-10000	0	-10000	0	0
BAX	0.016	0.02	-10000	0	-0.25	3	3
MAPK14	0.018	0.012	-10000	0	-0.25	1	1
BAD	0.017	0.023	-10000	0	-0.52	1	1
CABIN1/MEF2D	0.012	0.09	-10000	0	-0.39	11	11
Calcineurin A alpha-beta B1/BCL2	-0.11	0.22	-10000	0	-0.47	144	144
FKBP8	0.017	0.012	-10000	0	-0.25	1	1
activation-induced cell death of T cells	-0.012	0.089	0.38	11	-10000	0	11
KPNB1	0.012	0.057	-10000	0	-0.52	6	6
KPNA2	-0.001	0.084	-10000	0	-0.34	27	27
XPO1	0.018	0	-10000	0	-10000	0	0
SFN	-0.015	0.12	-10000	0	-0.45	37	37
MAP3K8	-0.036	0.15	-10000	0	-0.39	70	70
NFAT4/CK1 alpha	0.011	0.074	-10000	0	-0.24	37	37
MEF2D/NFAT1/Cbp/p300	0.057	0.059	-10000	0	-0.38	2	2
CABIN1	0.003	0.095	-10000	0	-0.39	13	13
CALM1	0.018	0.001	-10000	0	-10000	0	0
RAN	0.017	0.012	-10000	0	-0.25	1	1
MAP3K1	-0.03	0.14	-10000	0	-0.42	58	58
CAMK4	0.011	0.052	-10000	0	-0.33	11	11
mol:Ca2+	0.001	0.002	-10000	0	-10000	0	0
MAPK3	0.016	0.026	-10000	0	-0.39	2	2
YWHAH	0.013	0.048	-10000	0	-0.47	5	5
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.01	0.11	-10000	0	-0.37	39	39
YWHAB	0.015	0.037	-10000	0	-0.39	4	4
MAPK8	0.015	0.041	-10000	0	-0.52	3	3
MAPK9	-0.006	0.11	-10000	0	-0.51	24	24
YWHAG	0.017	0.017	-10000	0	-0.25	2	2
FKBP1A	0.017	0.017	-10000	0	-0.25	2	2
NFAT1-c-4/YWHAQ	0.051	0.067	-10000	0	-0.28	1	1
PRKCH	0.011	0.056	-10000	0	-0.42	8	8
CABIN1/Cbp/p300	0.023	0.042	-10000	0	-0.37	6	6
CASP3	0.018	0.001	-10000	0	-10000	0	0
PIM1	0.013	0.035	-10000	0	-0.25	9	9
Calcineurin A alpha-beta B1/FKBP12/FK506	0.012	0.009	-10000	0	-0.14	2	2
apoptosis	-0.026	0.046	-10000	0	-0.32	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.033	0.052	-10000	0	-0.33	1	1
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.01	0.06	-10000	0	-0.43	9	9
JNK2/NFAT4	0.013	0.062	-10000	0	-0.28	23	23
BAD/BCL-XL	0.026	0.017	-10000	0	-0.37	1	1
PRKCD	0.014	0.042	-10000	0	-0.45	4	4
NUP214	0.016	0.026	-10000	0	-0.39	2	2
PRKCZ	0	0.001	-10000	0	-10000	0	0
PRKCA	0.014	0.033	-10000	0	-0.25	8	8
PRKCG	0.018	0	-10000	0	-10000	0	0
PRKCQ	-0.014	0.1	-10000	0	-0.31	51	51
FKBP38/BCL2	-0.07	0.16	-10000	0	-0.37	115	115
EP300	0.014	0.047	-10000	0	-0.52	4	4
PRKCB1	-0.052	0.16	-10000	0	-0.39	90	90
CSNK2A1	0.017	0.023	-10000	0	-0.52	1	1
NFATc/JNK1	0.041	0.073	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0.025	0.007	-10000	0	-10000	0	0
FKBP12/FK506	0.012	0.011	-10000	0	-0.17	2	2
CSNK1A1	0.022	0.015	-10000	0	-0.31	1	1
CaM/Ca2+/CAMK IV	0.021	0.032	-10000	0	-0.31	3	3
NFATc/ERK1	0.041	0.073	-10000	0	-0.49	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.019	0.091	-10000	0	-0.42	10	10
NR4A1	0.052	0.066	-10000	0	-0.51	2	2
GSK3B	0.018	0.001	-10000	0	-10000	0	0
positive T cell selection	0.017	0.006	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.027	0.036	-10000	0	-0.25	2	2
RCH1/ KPNB1	0.009	0.074	-10000	0	-0.38	15	15
YWHAQ	0.014	0.039	-10000	0	-0.36	5	5
PRKACA	0.018	0.001	-10000	0	-10000	0	0
AKAP5	-0.033	0.15	-10000	0	-0.42	61	61
MEF2D	0.018	0.001	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.017	0.017	-10000	0	-0.25	2	2
NFATc/p38 alpha	0.042	0.07	-10000	0	-10000	0	0
CREBBP	0.016	0.033	-10000	0	-0.52	2	2
BCL2	-0.11	0.22	-10000	0	-0.47	144	144

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.011	0.053	-9999	-0.31	13	13
ADCY5	-0.01	0.074	-9999	-0.32	15	15
ADCY6	0.014	0.042	-9999	-0.31	8	8
ADCY7	0.007	0.06	-9999	-0.32	14	14
ADCY1	0.015	0.038	-9999	-0.31	6	6
ADCY2	-0.03	0.11	-9999	-0.33	51	51
ADCY3	0.01	0.054	-9999	-0.31	13	13
ADCY8	0.011	0.046	-9999	-0.31	7	7
PRKCE	0.007	0.044	-9999	-0.31	9	9
ADCY9	0.002	0.075	-9999	-0.33	24	24
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.002	0.072	-9999	-0.31	14	14

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.014	0.044	-9999	-0.41	5	5
ITGB7	0.018	0	-9999	-10000	0	0
ITGA4	-0.007	0.1	-9999	-0.39	32	32
alpha4/beta7 Integrin	0.009	0.074	-9999	-0.37	16	16
alpha4/beta1 Integrin	0.006	0.084	-9999	-0.41	17	17

×

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

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
MET/RANBP9	0.014	0.053	-10000	0	-0.37	4	4
CRKL	0.02	0.086	-10000	0	-0.45	11	11
mol:PIP3	-0.004	0.091	0.46	19	-10000	0	19
AKT1	0.007	0.068	0.34	18	-0.28	4	22
PTK2B	0.017	0.017	-10000	0	-0.25	2	2
RAPGEF1	0.026	0.082	-10000	0	-0.44	10	10
RANBP10	0.018	0	-10000	0	-10000	0	0
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
HGF/MET/SHIP2	0.016	0.071	-10000	0	-0.31	18	18
MAP3K5	0.018	0.099	-10000	0	-0.4	15	15
HGF/MET/CIN85/CBL/ENDOPHILINS	0.021	0.079	-10000	0	-0.29	24	24
AP1	-0.087	0.16	-10000	0	-0.37	107	107
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.017	0.023	-10000	0	-0.52	1	1
apoptosis	-0.14	0.3	-10000	0	-0.74	100	100
STAT3 (dimer)	0.029	0.058	-10000	0	-0.29	2	2
GAB1/CRKL/SHP2/PI3K	0.029	0.098	-10000	0	-0.42	13	13
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.03	0.081	-10000	0	-0.46	9	9
PTPN11	0.017	0.023	-10000	0	-0.52	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.016	0.026	-10000	0	-0.39	2	2
PTEN	-0.002	0.1	-10000	0	-0.52	19	19
ELK1	-0.005	0.036	0.25	3	-0.17	6	9
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.023	0.045	-10000	0	-0.23	7	7
PAK1	-0.005	0.089	0.31	18	-0.26	29	47
HGF/MET/RANBP10	0.02	0.063	-10000	0	-0.31	13	13
HRAS	0.025	0.077	-10000	0	-0.52	6	6
DOCK1	0.021	0.093	-10000	0	-0.49	10	10
GAB1	0.016	0.087	-10000	0	-0.48	11	11
CRK	0.021	0.084	-10000	0	-0.47	10	10
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.021	0.083	-10000	0	-0.49	12	12
JUN	-0.034	0.15	-10000	0	-0.46	57	57
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.005	0.05	-10000	0	-0.24	17	17
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
cell morphogenesis	0.039	0.088	-10000	0	-0.36	9	9
GRB2/SHC	0.024	0.049	-10000	0	-0.23	11	11
FOS	-0.11	0.2	-10000	0	-0.37	171	171
GLMN	-0.001	0.014	-10000	0	-0.25	1	1
cell motility	-0.005	0.036	0.25	3	-0.17	6	9
HGF/MET/MUC20	0.008	0.062	-10000	0	-0.32	13	13
cell migration	0.024	0.048	-10000	0	-0.23	11	11
GRB2	0.016	0.024	-10000	0	-0.25	4	4
CBL	0.017	0.012	-10000	0	-0.25	1	1
MET/RANBP10	0.014	0.053	-10000	0	-0.37	4	4
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.025	0.059	-10000	0	-0.3	2	2
MET/MUC20	0.001	0.052	-10000	0	-0.2	31	31
RAP1B	0.03	0.08	-10000	0	-0.41	10	10
RAP1A	0.03	0.087	-10000	0	-0.44	12	12
HGF/MET/RANBP9	0.019	0.063	-10000	0	-0.31	13	13
RAF1	0.031	0.073	-10000	0	-0.52	5	5
STAT3	0.029	0.059	-10000	0	-0.29	2	2
cell proliferation	0.037	0.07	-10000	0	-0.32	13	13
RPS6KB1	0.009	0.023	-10000	0	-10000	0	0
MAPK3	-0.01	0.04	0.66	1	-10000	0	1
MAPK1	-0.009	0.055	0.76	2	-10000	0	2
RANBP9	0.017	0.012	-10000	0	-0.25	1	1
MAPK8	0.025	0.093	-10000	0	-0.4	8	8
SRC	0.029	0.058	-10000	0	-0.28	2	2
PI3K	0.011	0.077	-10000	0	-0.26	29	29
MET/Glomulin	0.005	0.047	-10000	0	-0.17	32	32
SOS1	0.017	0.023	-10000	0	-0.52	1	1
MAP2K1	0.037	0.069	-10000	0	-0.51	4	4
MET	0	0.075	-10000	0	-0.29	31	31
MAP4K1	0.03	0.081	-10000	0	-0.46	9	9
PTK2	0.016	0.029	-10000	0	-0.34	3	3
MAP2K2	0.036	0.073	-10000	0	-0.5	5	5
BAD	0.013	0.064	0.32	18	-0.26	5	23
MAP2K4	0.015	0.1	-10000	0	-0.35	17	17
SHP2/GRB2/SOS1/GAB1	-0.016	0.067	-10000	0	-0.39	12	12
INPPL1	0.012	0.055	-10000	0	-0.44	7	7
PXN	0.018	0	-10000	0	-10000	0	0
SH3KBP1	0	0.086	-10000	0	-0.38	23	23
HGS	0.012	0.048	-10000	0	-0.25	11	11
PLCgamma1/PKC	0.012	0.019	-10000	0	-0.27	2	2
HGF	0.008	0.069	-10000	0	-0.45	11	11
RASA1	0.004	0.078	-10000	0	-0.42	16	16
NCK1	0.011	0.045	-10000	0	-0.28	12	12
PTPRJ	0.012	0.055	-10000	0	-0.44	7	7
NCK/PLCgamma1	0.024	0.055	-10000	0	-0.24	11	11
PDPK1	0.003	0.07	0.37	18	-10000	0	18
HGF/MET/SHIP	0.008	0.062	-10000	0	-0.32	13	13

×

EPO signaling pathway

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
BCL2L1	-0.029	0.17	-10000	0	-0.46	9	9
CRKL	0.006	0.074	-10000	0	-0.3	8	8
mol:DAG	0.006	0.083	-10000	0	-0.28	3	3
HRAS	0.024	0.075	-10000	0	-0.41	2	2
MAPK8	0.009	0.058	-10000	0	-0.28	4	4
RAP1A	0.005	0.077	-10000	0	-0.32	9	9
GAB1	0.002	0.08	-10000	0	-0.31	9	9
MAPK14	0.011	0.054	-10000	0	-0.24	1	1
EPO	-0.025	0.098	-10000	0	-0.26	80	80
PLCG1	0.006	0.084	-10000	0	-0.29	3	3
EPOR/TRPC2/IP3 Receptors	0.013	0.024	-10000	0	-0.27	3	3
RAPGEF1	0.018	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.001	0.073	-10000	0	-0.32	10	10
GAB1/SHC/GRB2/SOS1	0.02	0.074	-10000	0	-0.43	2	2
EPO/EPOR (dimer)	-0.005	0.071	-10000	0	-0.32	2	2
IRS2	-0.013	0.1	-10000	0	-0.33	26	26
STAT1	-0.026	0.14	-10000	0	-0.33	52	52
STAT5B	-0.002	0.1	-10000	0	-0.32	3	3
cell proliferation	0.016	0.054	-10000	0	-0.27	3	3
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.031	0.066	-10000	0	-0.31	12	12
TEC	0.005	0.074	-10000	0	-0.27	11	11
SOCS3	0.005	0.074	-10000	0	-0.38	17	17
STAT1 (dimer)	-0.026	0.14	-10000	0	-0.32	52	52
JAK2	0.008	0.054	-10000	0	-0.32	12	12
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
EPO/EPOR (dimer)/JAK2	0.015	0.083	-10000	0	-0.29	6	6
EPO/EPOR	-0.005	0.071	-10000	0	-0.32	2	2
LYN	0.012	0.033	-10000	0	-0.26	7	7
TEC/VAV2	0.014	0.076	-10000	0	-0.29	6	6
elevation of cytosolic calcium ion concentration	0.013	0.023	-10000	0	-0.27	3	3
SHC1	0.017	0.023	-10000	0	-0.52	1	1
EPO/EPOR (dimer)/LYN	0.009	0.066	-10000	0	-0.26	2	2
mol:IP3	0.006	0.083	-10000	0	-0.28	3	3
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.017	0.11	-10000	0	-0.32	39	39
SH2B3	0.015	0.024	-10000	0	-0.52	1	1
NFKB1	0.01	0.055	-10000	0	-0.27	2	2
EPO/EPOR (dimer)/JAK2/SOCS3	-0.004	0.05	0.26	1	-0.23	11	12
PTPN6	0	0.072	-10000	0	-0.29	6	6
TEC/VAV2/GRB2	0.021	0.074	-10000	0	-0.28	6	6
EPOR	0.013	0.024	-10000	0	-0.27	3	3
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.075	-10000	0	-0.44	2	2
SOS1	0.017	0.023	-10000	0	-0.52	1	1
PLCG2	-0.017	0.11	-10000	0	-0.32	55	55
CRKL/CBL/C3G	0.023	0.073	-10000	0	-0.36	3	3
VAV2	0.007	0.071	-10000	0	-0.3	4	4
CBL	0.008	0.07	-10000	0	-0.3	4	4
SHC/Grb2/SOS1	-0.021	0.044	-10000	0	-0.28	4	4
STAT5A	-0.005	0.11	-10000	0	-0.31	9	9
GRB2	0.016	0.024	-10000	0	-0.25	4	4
STAT5 (dimer)	-0.013	0.15	-10000	0	-0.35	38	38
LYN/PLCgamma2	-0.002	0.082	-10000	0	-0.36	16	16
PTPN11	0.017	0.023	-10000	0	-0.52	1	1
BTK	-0.005	0.092	-10000	0	-0.31	22	22
BCL2	-0.15	0.38	-10000	0	-0.86	117	117

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.041	0.037	-10000	0	-0.27	7	7
HDAC3	0.018	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.011	-10000	0	-0.22	1	1
GATA1/HDAC4	0.026	0.017	-10000	0	-0.37	1	1
GATA1/HDAC5	0.026	0.017	-10000	0	-0.37	1	1
GATA2/HDAC5	0.008	0.068	-10000	0	-0.37	10	10
HDAC5/BCL6/BCoR	0.016	0.078	-10000	0	-0.3	28	28
HDAC9	0.011	0.045	-10000	0	-0.28	12	12
Glucocorticoid receptor/Hsp90/HDAC6	0.021	0.068	-10000	0	-0.3	21	21
HDAC4/ANKRA2	0.013	0.072	-10000	0	-0.37	18	18
HDAC5/YWHAB	0.023	0.032	-10000	0	-0.37	3	3
NPC/RanGAP1/SUMO1/Ubc9	0.023	0.013	-10000	0	-0.2	1	1
GATA2	-0.007	0.093	-10000	0	-0.31	40	40
HDAC4/RFXANK	0.025	0.019	-10000	0	-0.37	1	1
BCOR	0.009	0.07	-10000	0	-0.52	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.015	0.037	-10000	0	-0.39	4	4
HDAC5	0.017	0.023	-10000	0	-0.52	1	1
GNB1/GNG2	0.021	0.043	-10000	0	-0.37	6	6
Histones	0.02	0.07	-10000	0	-0.25	29	29
ADRBK1	0.018	0	-10000	0	-10000	0	0
HDAC4	0.017	0.023	-10000	0	-0.52	1	1
XPO1	0.018	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.013	0.072	-10000	0	-0.37	18	18
HDAC4/Ubc9	0.026	0.017	-10000	0	-0.37	1	1
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.024	0.027	-10000	0	-0.37	2	2
TUBA1B	0.018	0	-10000	0	-10000	0	0
HDAC6	0.018	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.025	0.019	-10000	0	-0.37	1	1
CAMK4	0.011	0.052	-10000	0	-0.33	11	11
Tubulin/HDAC6	0.022	0.063	-10000	0	-0.3	17	17
SUMO1	0.018	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.015	0.037	-10000	0	-0.39	4	4
GATA1	0.018	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.016	0.029	-10000	0	-0.34	3	3
NR3C1	-0.001	0.098	-10000	0	-0.51	19	19
SUMO1/HDAC4	0.036	0.019	-10000	0	-0.31	1	1
SRF	0.016	0.024	-10000	0	-0.25	4	4
HDAC4/YWHAB	0.023	0.032	-10000	0	-0.37	3	3
Tubulin	0.011	0.073	-10000	0	-0.37	17	17
HDAC4/14-3-3 E	0.024	0.03	-10000	0	-0.44	2	2
GNB1	0.013	0.052	-10000	0	-0.52	5	5
RANGAP1	0.014	0.037	-10000	0	-0.29	7	7
BCL6/BCoR	0.004	0.089	-10000	0	-0.37	27	27
HDAC4/HDAC3/SMRT (N-CoR2)	0.035	0.015	-10000	0	-0.3	1	1
HDAC4/SRF	0.03	0.037	-10000	0	-0.3	4	4
HDAC4/ER alpha	-0.1	0.18	-10000	0	-0.37	151	151
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.02	0.069	-10000	0	-0.25	29	29
cell motility	0.022	0.063	-10000	0	-0.3	17	17
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.018	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.013	0	-10000	0	-10000	0	0
BCL6	-0.004	0.1	-10000	0	-0.45	24	24
HDAC4/CaMK II delta B	0.017	0.023	-10000	0	-0.52	1	1
Hsp90/HDAC6	0.023	0.033	-10000	0	-0.37	3	3
ESR1	-0.16	0.24	-10000	0	-0.46	199	199
HDAC6/HDAC11	0.004	0.089	-10000	0	-0.37	28	28
Ran/GTP/Exportin 1	0.039	0.013	-10000	0	-10000	0	0
NPC	0.01	0.008	-10000	0	-10000	0	0
MEF2C	-0.014	0.12	-10000	0	-0.45	36	36
RAN	0.017	0.012	-10000	0	-0.25	1	1
HDAC4/MEF2C	0.035	0.069	-10000	0	-0.24	28	28
GNG2	0.016	0.029	-10000	0	-0.34	3	3
NCOR2	0.018	0	-10000	0	-10000	0	0
TUBB2A	-0.004	0.1	-10000	0	-0.43	26	26
HDAC11	-0.012	0.12	-10000	0	-0.5	31	31
HSP90AA1	0.013	0.045	-10000	0	-0.39	6	6
RANBP2	0.017	0.017	-10000	0	-0.25	2	2
ANKRA2	0	0.095	-10000	0	-0.52	17	17
RFXANK	0.017	0.012	-10000	0	-0.25	1	1
nuclear import	-0.032	0.035	0.31	5	-10000	0	5

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.014	0.047	-10000	0	-0.52	4	4
Rac1/GDP	0.003	0.012	-10000	0	-10000	0	0
DOCK1	0.006	0.078	-10000	0	-0.5	12	12
ITGA4	-0.007	0.1	-10000	0	-0.39	32	32
RAC1	0.018	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.009	0.074	-10000	0	-0.37	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.016	0.033	-10000	0	-0.52	2	2
alpha4/beta1 Integrin	0.019	0.073	-10000	0	-0.34	17	17
alpha4/beta7 Integrin/Paxillin	0.028	0.058	-10000	0	-0.27	16	16
lamellipodium assembly	0.028	0.091	-10000	0	-0.35	22	22
PIK3CA	0.016	0.029	-10000	0	-0.34	3	3
PI3K	0.005	0.082	-10000	0	-0.37	21	21
ARF6	0.016	0.033	-10000	0	-0.52	2	2
TLN1	0.017	0.023	-10000	0	-0.52	1	1
PXN	0.025	0	-10000	0	-10000	0	0
PIK3R1	-0.009	0.11	-10000	0	-0.42	33	33
ARF6/GTP	0.031	0.061	-10000	0	-0.47	2	2
cell adhesion	0.033	0.064	-10000	0	-0.27	18	18
CRKL/CBL	0.023	0.035	-10000	0	-0.37	4	4
alpha4/beta1 Integrin/Paxillin	0.026	0.067	-10000	0	-0.3	17	17
ITGB1	0.014	0.044	-10000	0	-0.41	5	5
ITGB7	0.018	0	-10000	0	-10000	0	0
ARF6/GDP	0.001	0.034	-10000	0	-0.51	2	2
alpha4/beta1 Integrin/Paxillin/VCAM1	0.015	0.1	-10000	0	-0.3	40	40
p130Cas/Crk/Dock1	0.027	0.054	-10000	0	-0.3	13	13
VCAM1	-0.022	0.13	-10000	0	-0.42	48	48
alpha4/beta1 Integrin/Paxillin/Talin	0.035	0.065	-10000	0	-0.28	18	18
alpha4/beta1 Integrin/Paxillin/GIT1	0.034	0.066	-10000	0	-0.28	18	18
BCAR1	0.017	0.012	-10000	0	-0.25	1	1
mol:GDP	-0.032	0.065	0.27	18	-10000	0	18
CBL	0.017	0.012	-10000	0	-0.25	1	1
PRKACA	0.018	0	-10000	0	-10000	0	0
GIT1	0.014	0.035	-10000	0	-0.3	6	6
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.035	0.065	-10000	0	-0.28	18	18
Rac1/GTP	-0.019	0.087	-10000	0	-0.38	22	22

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	-0.009	0.07	0.39	11	-10000	0	11
KIRREL	0.007	0.075	-10000	0	-0.53	10	10
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.01	0.07	-10000	0	-0.39	11	11
PLCG1	0.016	0.026	-10000	0	-0.39	2	2
ARRB2	0.018	0	-10000	0	-10000	0	0
WASL	0.01	0.066	-10000	0	-0.52	8	8
Nephrin/NEPH1/podocin/CD2AP	0.028	0.059	-10000	0	-0.27	14	14
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.025	0.06	-10000	0	-0.29	5	5
FYN	0.014	0.059	-10000	0	-0.25	20	20
mol:Ca2+	0.027	0.06	-10000	0	-0.29	13	13
mol:DAG	0.028	0.06	-10000	0	-0.29	13	13
NPHS2	0.015	0.036	-10000	0	-0.43	3	3
mol:IP3	0.028	0.06	-10000	0	-0.29	13	13
regulation of endocytosis	0.028	0.058	-10000	0	-0.25	13	13
Nephrin/NEPH1/podocin/Cholesterol	0.018	0.056	-10000	0	-0.28	13	13
establishment of cell polarity	0.009	0.07	-10000	0	-0.39	11	11
Nephrin/NEPH1/podocin/NCK1-2	0.035	0.06	-10000	0	-0.25	14	14
Nephrin/NEPH1/beta Arrestin2	0.029	0.059	-10000	0	-0.26	13	13
NPHS1	0.004	0.061	-10000	0	-0.26	25	25
Nephrin/NEPH1/podocin	0.02	0.061	-10000	0	-0.25	20	20
TJP1	0.013	0.052	-10000	0	-0.52	5	5
NCK1	0.011	0.045	-10000	0	-0.28	12	12
NCK2	0.015	0.026	-10000	0	-0.25	5	5
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.029	0.061	-10000	0	-0.3	13	13
CD2AP	0.016	0.029	-10000	0	-0.34	3	3
Nephrin/NEPH1/podocin/GRB2	0.028	0.058	-10000	0	-0.27	13	13
GRB2	0.016	0.024	-10000	0	-0.25	4	4
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	0.012	0.068	-10000	0	-0.27	24	24
cytoskeleton organization	0.029	0.063	-10000	0	-0.27	14	14
Nephrin/NEPH1	0.011	0.049	-10000	0	-0.27	11	11
Nephrin/NEPH1/ZO-1	0.019	0.066	-10000	0	-0.31	16	16

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.002	0.081	-9999	-0.36	22	22
Aurora C/Aurora B/INCENP	0.016	0.061	-9999	-0.28	14	14
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.007	0.037	-9999	-0.52	2	2
AURKB	0.009	0.056	-9999	-0.31	14	14
AURKC	0.008	0.053	-9999	-0.27	18	18

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.017	0.1	-10000	0	-1.3	1	1
CLOCK	0.02	0.024	-10000	0	-0.52	1	1
TIMELESS/CRY2	0.041	0.06	-10000	0	-1.2	1	1
DEC1/BMAL1	0.015	0.072	-10000	0	-0.39	15	15
ATR	0.017	0.012	-10000	0	-0.25	1	1
NR1D1	0.036	0.045	-10000	0	-10000	0	0
ARNTL	0.009	0.078	-10000	0	-0.49	12	12
TIMELESS	0.036	0.065	-10000	0	-1.3	1	1
NPAS2	-0.004	0.094	-10000	0	-0.32	39	39
CRY2	0.017	0.012	-10000	0	-0.25	1	1
mol:CO	-0.014	0.012	0.14	1	-10000	0	1
CHEK1	-0.046	0.16	-10000	0	-0.38	84	84
mol:HEME	0.014	0.012	-10000	0	-0.14	1	1
PER1	0.014	0.037	-10000	0	-0.29	7	7
BMAL/CLOCK/NPAS2	0.03	0.082	-10000	0	-0.32	21	21
BMAL1/CLOCK	0.042	0.076	-10000	0	-0.54	2	2
S phase of mitotic cell cycle	0.017	0.1	-10000	0	-1.3	1	1
TIMELESS/CHEK1/ATR	0.017	0.1	-10000	0	-1.4	1	1
mol:NADPH	0.014	0.012	-10000	0	-0.14	1	1
PER1/TIMELESS	0.039	0.063	-10000	0	-1.2	1	1
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.011	0.057	-10000	0	-0.4	9	9

×

S1P5 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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.01	0.078	0.29	16	-10000	0	16
GNAI2	0.006	0.075	-10000	0	-0.48	12	12
S1P/S1P5/G12	0.012	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.016	0.024	-10000	0	-0.25	4	4
RhoA/GTP	0.01	0.08	-10000	0	-0.29	16	16
negative regulation of cAMP metabolic process	0.008	0.072	-10000	0	-0.29	12	12
GNAZ	0.001	0.088	-10000	0	-0.44	19	19
GNAI3	0.018	0	-10000	0	-10000	0	0
GNA12	0.018	0	-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	0.008	0.072	-10000	0	-0.29	12	12
RhoA/GDP	0.004	0.058	-10000	0	-0.38	12	12
RHOA	0.005	0.08	-10000	0	-0.52	12	12
GNAI1	-0.017	0.12	-10000	0	-0.38	46	46

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.04	0.082	-9999	-1.3	1	1
PLK1	0.03	0.18	-9999	-0.68	9	9
CDKN1B	0.062	0.17	-9999	-0.49	29	29
FOXO3	0.022	0.19	-9999	-0.57	21	21
KAT2B	0.003	0.02	-9999	-0.051	16	16
FOXO1/SIRT1	0.035	0.067	-9999	-0.37	5	5
CAT	0.024	0.2	-9999	-0.86	12	12
CTNNB1	0.001	0.09	-9999	-0.45	19	19
AKT1	0.019	0.057	-9999	-0.36	9	9
FOXO1	0.035	0.067	-9999	-0.36	5	5
MAPK10	0.014	0.073	-9999	-0.26	27	27
mol:GTP	0.001	0.003	-9999	-10000	0	0
FOXO4	0.061	0.1	-9999	-0.4	5	5
response to oxidative stress	0.008	0.022	-9999	-0.052	17	17
FOXO3A/SIRT1	0.035	0.16	-9999	-0.49	19	19
XPO1	0.018	0.001	-9999	-10000	0	0
EP300	0.017	0.047	-9999	-0.52	4	4
BCL2L11	0.027	0.038	-9999	-10000	0	0
FOXO1/SKP2	0.035	0.071	-9999	-0.42	5	5
mol:GDP	0.008	0.022	-9999	-0.052	17	17
RAN	0.018	0.012	-9999	-0.25	1	1
GADD45A	0.038	0.22	-9999	-0.9	21	21
YWHAQ	0.014	0.039	-9999	-0.36	5	5
FOXO1/14-3-3 family	0.066	0.061	-9999	-0.34	2	2
MST1	0.02	0.03	-9999	-0.29	3	3
CSNK1D	0.018	0	-9999	-10000	0	0
CSNK1E	0.017	0.012	-9999	-0.25	1	1
FOXO4/14-3-3 family	0.04	0.081	-9999	-0.56	1	1
YWHAB	0.015	0.037	-9999	-0.39	4	4
MAPK8	0.034	0.038	-9999	-0.26	7	7
MAPK9	0.023	0.067	-9999	-0.25	27	27
YWHAG	0.017	0.017	-9999	-0.25	2	2
YWHAE	0.016	0.029	-9999	-0.34	3	3
YWHAZ	0.017	0.017	-9999	-0.25	2	2
SIRT1	0.018	0.035	-9999	-0.35	3	3
SOD2	0.066	0.17	-9999	-0.66	8	8
RBL2	0.046	0.16	-9999	-0.82	6	6
RAL/GDP	0.031	0.034	-9999	-0.31	4	4
CHUK	0.009	0.083	-9999	-0.5	13	13
Ran/GTP	0.016	0.009	-9999	-0.16	1	1
CSNK1G2	0.016	0.033	-9999	-0.52	2	2
RAL/GTP	0.036	0.035	-9999	-0.28	4	4
CSNK1G1	0.017	0.012	-9999	-0.25	1	1
FASLG	-0.12	0.41	-9999	-1.4	49	49
SKP2	0.007	0.052	-9999	-0.25	20	20
USP7	0.018	0.012	-9999	-0.26	1	1
IKBKB	0.015	0.051	-9999	-0.31	10	10
CCNB1	-0.02	0.32	-9999	-1.1	38	38
FOXO1-3a-4/beta catenin	0.068	0.17	-9999	-0.41	22	22
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.071	-9999	-0.41	5	5
CSNK1A1	0.017	0.023	-9999	-0.52	1	1
SGK1	0.003	0.02	-9999	-0.051	16	16
CSNK1G3	0.013	0.052	-9999	-0.52	5	5
Ran/GTP/Exportin 1	0.028	0.011	-9999	-10000	0	0
ZFAND5	0.067	0.09	-9999	-0.39	1	1
SFN	-0.015	0.12	-9999	-0.45	37	37
CDK2	0.015	0.047	-9999	-0.3	10	10
FOXO3A/14-3-3	0.043	0.08	-9999	-0.42	3	3
CREBBP	0.019	0.033	-9999	-0.52	2	2
FBXO32	-0.007	0.3	-9999	-1.2	23	23
BCL6	0.016	0.26	-9999	-1.2	19	19
RALB	0.015	0.047	-9999	-0.52	4	4
RALA	0.019	0.002	-9999	-10000	0	0
YWHAH	0.013	0.048	-9999	-0.47	5	5

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.015	0.065	-9999	-0.37	14	14
FBXW11	0.015	0.035	-9999	-0.43	3	3
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.015	0.035	-9999	-0.43	3	3
CHUK	0.005	0.081	-9999	-0.5	13	13
NF kappa B2 p100/RelB	0.034	0.074	-9999	-0.28	24	24
NFKB1	0.017	0.023	-9999	-0.52	1	1
MAP3K14	0.015	0.037	-9999	-0.39	4	4
NF kappa B1 p50/RelB	0.015	0.059	-9999	-0.37	10	10
RELB	0.003	0.078	-9999	-0.38	19	19
NFKB2	0.015	0.031	-9999	-0.32	4	4
NF kappa B2 p52/RelB	0.014	0.052	-9999	-0.31	11	11
regulation of B cell activation	0.014	0.052	-9999	-0.31	11	11

×

Regulation of cytoplasmic and nuclear SMAD2/3 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
SMAD4	0.009	0.067	-10000	0	-0.49	9	9
SMAD2	0.021	0.048	0.24	1	-0.23	9	10
SMAD3	0.032	0.056	-10000	0	-0.39	2	2
SMAD3/SMAD4	0.033	0.069	-10000	0	-0.34	9	9
SMAD4/Ubc9/PIASy	0.027	0.052	-10000	0	-0.3	12	12
SMAD2/SMAD2/SMAD4	0.031	0.061	-10000	0	-0.27	1	1
PPM1A	0.016	0.026	-10000	0	-0.39	2	2
CALM1	0.018	0	-10000	0	-10000	0	0
SMAD2/SMAD4	0.024	0.056	0.2	1	-0.23	17	18
MAP3K1	-0.03	0.14	-10000	0	-0.42	58	58
TRAP-1/SMAD4	0.02	0.049	-10000	0	-0.37	8	8
MAPK3	0.016	0.026	-10000	0	-0.39	2	2
MAPK1	0.016	0.033	-10000	0	-0.52	2	2
NUP214	0.016	0.026	-10000	0	-0.39	2	2
CTDSP1	0.016	0.033	-10000	0	-0.52	2	2
CTDSP2	0.014	0.044	-10000	0	-0.41	5	5
CTDSPL	0.011	0.062	-10000	0	-0.52	7	7
KPNB1	0.012	0.057	-10000	0	-0.52	6	6
TGFBRAP1	0.017	0.012	-10000	0	-0.25	1	1
UBE2I	0.018	0	-10000	0	-10000	0	0
NUP153	0.016	0.024	-10000	0	-0.25	4	4
KPNA2	-0.001	0.084	-10000	0	-0.34	27	27
PIAS4	0.013	0.049	-10000	0	-0.43	6	6

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.018	0.036	-9999	-0.43	3	3
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.06	0.078	-9999	-0.38	4	4
ERC1	0.011	0.056	-9999	-0.42	8	8
RIP2/NOD2	-0.031	0.13	-9999	-0.37	66	66
NFKBIA	0.042	0.051	-9999	-0.54	3	3
BIRC2	0.016	0.02	-9999	-0.25	3	3
IKBKB	0.012	0.047	-9999	-0.31	10	10
RIPK2	0.013	0.04	-9999	-0.28	9	9
IKBKG	0.016	0.091	-9999	-0.51	5	5
IKK complex/A20	0.027	0.1	-9999	-0.44	9	9
NEMO/A20/RIP2	0.013	0.04	-9999	-0.28	9	9
XPO1	0.018	0	-9999	-10000	0	0
NEMO/ATM	0.024	0.088	-9999	-0.48	5	5
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.017	0.012	-9999	-0.25	1	1
Exportin 1/RanGTP	0.024	0.007	-9999	-10000	0	0
IKK complex/ELKS	-0.028	0.077	-9999	-0.42	10	10
BCL10/MALT1/TRAF6	0.031	0.041	-9999	-0.38	4	4
NOD2	-0.056	0.18	-9999	-0.46	81	81
NFKB1	0.019	0.025	-9999	-0.52	1	1
RELA	0.02	0.009	-9999	-10000	0	0
MALT1	0.011	0.053	-9999	-0.37	9	9
cIAP1/UbcH5C	0.025	0.014	-9999	-10000	0	0
ATM	0.017	0.012	-9999	-0.25	1	1
TNF/TNFR1A	0.009	0.071	-9999	-0.37	14	14
TRAF6	0.017	0.023	-9999	-0.52	1	1
PRKCA	0.014	0.033	-9999	-0.25	8	8
CHUK	0.005	0.081	-9999	-0.5	13	13
UBE2D3	0.018	0	-9999	-10000	0	0
TNF	-0.004	0.094	-9999	-0.36	31	31
NF kappa B1 p50/RelA	0.045	0.036	-9999	-0.28	6	6
BCL10	0.017	0.012	-9999	-0.25	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.042	0.051	-9999	-0.54	3	3
beta TrCP1/SCF ubiquitin ligase complex	0.018	0.036	-9999	-0.42	3	3
TNFRSF1A	0.016	0.033	-9999	-0.52	2	2
IKK complex	0.025	0.1	-9999	-0.46	9	9
CYLD	0.014	0.044	-9999	-0.41	5	5
IKK complex/PKC alpha	0.03	0.1	-9999	-0.49	7	7

×

Ephrin A reverse signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.015	0.047	-9999	-0.31	8	8
EFNA5	0.006	0.068	-9999	-0.35	17	17
FYN	0.015	0.055	-9999	-0.28	15	15
neuron projection morphogenesis	0.015	0.047	-9999	-0.31	8	8
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	0.015	0.047	-9999	-0.31	8	8
EPHA5	0.015	0.037	-9999	-0.39	4	4

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.025	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.04	0.016	-10000	0	-0.27	1	1
CDKN1B	0.021	0.079	-10000	0	-0.37	8	8
CDKN1A	0.025	0.072	-10000	0	-0.44	6	6
FRAP1	0.018	0	-10000	0	-10000	0	0
PRKDC	0.012	0.045	-10000	0	-0.31	9	9
FOXO3	0.033	0.062	-10000	0	-0.46	6	6
AKT1	0.03	0.053	-10000	0	-0.43	6	6
BAD	0.017	0.023	-10000	0	-0.52	1	1
AKT3	0.007	0.046	-10000	0	-0.32	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.035	0.053	-10000	0	-0.39	7	7
AKT1/ASK1	0.018	0.081	-10000	0	-0.36	10	10
BAD/YWHAZ	0.035	0.018	-10000	0	-0.3	1	1
RICTOR	0.018	0	-10000	0	-10000	0	0
RAF1	0.017	0.012	-10000	0	-0.25	1	1
JNK cascade	-0.017	0.079	0.35	10	-10000	0	10
TSC1	0.036	0.051	-10000	0	-0.4	6	6
YWHAZ	0.017	0.017	-10000	0	-0.25	2	2
AKT1/RAF1	0.038	0.052	-10000	0	-0.4	6	6
EP300	0.014	0.047	-10000	0	-0.52	4	4
mol:GDP	0.03	0.053	-10000	0	-0.42	6	6
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.035	0.056	-10000	0	-0.44	6	6
YWHAQ	0.014	0.039	-10000	0	-0.36	5	5
TBC1D4	0.011	0.063	-10000	0	-0.3	19	19
MAP3K5	-0.022	0.13	-10000	0	-0.42	47	47
MAPKAP1	0.016	0.026	-10000	0	-0.39	2	2
negative regulation of cell cycle	-0.034	0.048	0.24	3	-10000	0	3
YWHAH	0.013	0.048	-10000	0	-0.47	5	5
AKT1S1	0.032	0.063	-10000	0	-0.4	9	9
CASP9	0.035	0.053	-10000	0	-0.39	7	7
YWHAB	0.015	0.037	-10000	0	-0.39	4	4
p27Kip1/KPNA1	0.03	0.076	-10000	0	-0.36	7	7
GBL	0.015	0.035	-10000	0	-0.43	3	3
PDK1/Src/Hsp90	0.031	0.039	-10000	0	-0.3	6	6
YWHAE	0.016	0.029	-10000	0	-0.34	3	3
SRC	0.015	0.035	-10000	0	-0.43	3	3
AKT2/p21CIP1	0.03	0.068	-10000	0	-0.39	6	6
KIAA1303	0.015	0.031	-10000	0	-0.32	4	4
mTOR/RHEB/GTP/Raptor/GBL	0.038	0.041	-10000	0	-0.39	4	4
CHUK	0.03	0.068	-10000	0	-0.42	7	7
BAD/BCL-XL	0.052	0.051	-10000	0	-0.37	6	6
mTORC2	0.043	0.025	-10000	0	-0.27	3	3
AKT2	0.019	0.017	-10000	0	-0.32	1	1
FOXO1-3a-4/14-3-3 family	0.046	0.064	-10000	0	-0.28	5	5
PDPK1	0.016	0.026	-10000	0	-0.39	2	2
MDM2	0.033	0.054	-10000	0	-0.4	6	6
MAPKKK cascade	-0.038	0.051	0.39	6	-10000	0	6
MDM2/Cbp/p300	0.047	0.061	-10000	0	-0.4	6	6
TSC1/TSC2	0.041	0.055	-10000	0	-0.42	6	6
proteasomal ubiquitin-dependent protein catabolic process	0.045	0.058	-10000	0	-0.38	6	6
glucose import	0.011	0.064	-10000	0	-0.26	21	21
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.044	0.053	-10000	0	-0.38	5	5
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.011	0.064	-10000	0	-0.26	21	21
GSK3A	0.036	0.051	-10000	0	-0.4	6	6
FOXO1	0.027	0.068	-10000	0	-0.39	7	7
GSK3B	0.036	0.051	-10000	0	-0.4	6	6
SFN	-0.015	0.12	-10000	0	-0.45	37	37
G1/S transition of mitotic cell cycle	0.042	0.05	-10000	0	-0.38	6	6
p27Kip1/14-3-3 family	0.034	0.063	-10000	0	-0.37	4	4
PRKACA	0.018	0	-10000	0	-10000	0	0
KPNA1	0.018	0	-10000	0	-10000	0	0
HSP90AA1	0.013	0.045	-10000	0	-0.39	6	6
YWHAG	0.017	0.017	-10000	0	-0.25	2	2
RHEB	0.016	0.026	-10000	0	-0.39	2	2
CREBBP	0.016	0.033	-10000	0	-0.52	2	2

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.005	0.06	-10000	0	-0.26	24	24
CLTC	0.025	0.05	-10000	0	-0.49	3	3
calcium ion-dependent exocytosis	0.021	0.039	-10000	0	-0.28	4	4
Dynamin 2/GTP	0.025	0.027	-10000	0	-0.28	2	2
EXOC4	0.016	0.033	-10000	0	-0.52	2	2
CD59	0.021	0.05	-10000	0	-0.42	4	4
CPE	-0.021	0.11	-10000	0	-0.32	53	53
CTNNB1	0.001	0.09	-10000	0	-0.45	19	19
membrane fusion	0.021	0.041	-10000	0	-0.29	4	4
CTNND1	0.029	0.029	-10000	0	-0.25	3	3
DNM2	0.017	0.012	-10000	0	-0.25	1	1
mol:PI-4-5-P2	0.027	0.039	-10000	0	-0.35	3	3
TSHR	0.014	0.048	-10000	0	-0.31	11	11
INS	0.02	0.026	-10000	0	-0.51	1	1
BIN1	0.014	0.04	-10000	0	-0.34	6	6
mol:Choline	0.021	0.041	-10000	0	-0.29	4	4
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.017	0.03	-10000	0	-0.31	2	2
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.016	0.033	-10000	0	-0.52	2	2
mol:Ca2+	0.025	0.027	-10000	0	-0.27	2	2
JUP	0.023	0.046	-10000	0	-0.48	3	3
ASAP2/amphiphysin II	0.019	0.029	-10000	0	-0.28	4	4
ARF6/GTP	0.012	0.024	-10000	0	-0.38	2	2
CDH1	0	0.078	-10000	0	-0.46	3	3
clathrin-independent pinocytosis	0.012	0.024	-10000	0	-0.38	2	2
MAPK8IP3	0.006	0.075	-10000	0	-0.48	12	12
positive regulation of endocytosis	0.012	0.024	-10000	0	-0.38	2	2
EXOC2	-0.004	0.085	-10000	0	-0.31	35	35
substrate adhesion-dependent cell spreading	0.023	0.078	-10000	0	-0.24	37	37
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.014	0.035	-10000	0	-0.3	6	6
regulation of calcium-dependent cell-cell adhesion	-0.011	0.077	0.61	2	-10000	0	2
positive regulation of phagocytosis	0.018	0.032	-10000	0	-0.31	5	5
ARF6/GTP/JIP3	0.016	0.051	-10000	0	-0.31	12	12
ACAP1	0.019	0.035	-10000	0	-0.35	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.016	0.046	-10000	0	-0.52	2	2
clathrin heavy chain/ACAP1	0.028	0.048	-10000	0	-0.46	3	3
JIP4/KLC1	0.031	0.027	-10000	0	-0.28	3	3
EXOC1	0.018	0	-10000	0	-10000	0	0
exocyst	0.023	0.078	-10000	0	-0.25	37	37
RALA/GTP	0.013	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.021	0.029	-10000	0	-0.31	3	3
receptor recycling	0.012	0.024	-10000	0	-0.38	2	2
CTNNA1	0.03	0.028	-10000	0	-0.25	3	3
NME1	0.017	0.03	-10000	0	-0.31	2	2
clathrin coat assembly	0.025	0.05	-10000	0	-0.48	3	3
IL2RA	0.008	0.069	-10000	0	-0.35	7	7
VAMP3	0.018	0.032	-10000	0	-0.31	5	5
GLUT4/clathrin heavy chain/ACAP1	-0.008	0.04	-10000	0	-0.43	3	3
EXOC6	-0.012	0.12	-10000	0	-0.5	30	30
PLD1	0.015	0.05	-10000	0	-0.29	11	11
PLD2	0.021	0.033	-10000	0	-0.26	6	6
EXOC5	0.016	0.033	-10000	0	-0.52	2	2
PIP5K1C	0.028	0.039	-10000	0	-0.35	3	3
SDC1	0.004	0.072	-10000	0	-0.39	4	4
ARF6/GDP	0.018	0.03	-10000	0	-0.31	2	2
EXOC7	0.018	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.013	0.079	-10000	0	-0.64	2	2
mol:Phosphatidic acid	0.021	0.041	-10000	0	-0.29	4	4
endocytosis	-0.019	0.029	0.28	4	-10000	0	4
SCAMP2	0.015	0.035	-10000	0	-0.43	3	3
ADRB2	0.001	0.096	-10000	0	-0.62	4	4
EXOC3	0.017	0.012	-10000	0	-0.25	1	1
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.027	0.028	-10000	0	-0.27	2	2
KLC1	0.018	0	-10000	0	-10000	0	0
AVPR2	0.03	0.049	-10000	0	-0.45	3	3
RALA	0.018	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.022	0.076	-10000	0	-0.58	2	2

×

S1P4 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.016	0.024	-9999	-0.25	4	4
CDC42/GTP	0.016	0.067	-9999	-0.33	5	5
PLCG1	0.014	0.07	-9999	-0.32	6	6
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.006	0.075	-9999	-0.48	12	12
GNAI3	0.018	0	-9999	-10000	0	0
G12/G13	0.021	0.039	-9999	-0.37	4	4
cell migration	0.016	0.065	-9999	-0.32	5	5
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
MAPK3	0.014	0.069	-9999	-0.32	6	6
MAPK1	0.014	0.07	-9999	-0.31	7	7
S1P/S1P5/Gi	0.008	0.072	-9999	-0.29	12	12
GNAI1	-0.017	0.12	-9999	-0.38	46	46
CDC42/GDP	0.013	0	-9999	-10000	0	0
S1P/S1P5/G12	0.012	0	-9999	-10000	0	0
RHOA	0.017	0.056	-9999	-0.3	14	14
S1P/S1P4/Gi	0.008	0.072	-9999	-0.29	12	12
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.001	0.088	-9999	-0.44	19	19
S1P/S1P4/G12/G13	0.019	0.03	-9999	-0.28	4	4
GNA12	0.018	0	-9999	-10000	0	0
GNA13	0.011	0.055	-9999	-0.36	10	10
CDC42	0.018	0	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.038	0.06	-9999	-0.39	3	3
CaM/Ca2+	0.013	0	-9999	-10000	0	0
AKT1	0.011	0.053	-9999	-0.37	9	9
AKT2	0.017	0.012	-9999	-0.25	1	1
STXBP4	0.008	0.06	-9999	-0.32	15	15
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	0.033	0.053	-9999	-0.29	2	2
YWHAZ	0.017	0.017	-9999	-0.25	2	2
CALM1	0.018	0	-9999	-10000	0	0
YWHAQ	0.014	0.039	-9999	-0.36	5	5
TBC1D4	0.004	0.086	-9999	-0.38	21	21
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0.013	0.048	-9999	-0.47	5	5
YWHAB	0.015	0.037	-9999	-0.39	4	4
SNARE/Synip	0.029	0.042	-9999	-0.3	6	6
YWHAG	0.017	0.017	-9999	-0.25	2	2
ASIP	0	0	-9999	-10000	0	0
PRKCI	0.002	0.085	-9999	-0.43	18	18
AS160/CaM/Ca2+	0.013	0	-9999	-10000	0	0
RHOQ	0.012	0.053	-9999	-0.48	6	6
GYS1	0.031	0.027	-9999	-0.26	4	4
PRKCZ	0	0	-9999	-10000	0	0
TRIP10	0.013	0.048	-9999	-0.47	5	5
TC10/GTP/CIP4/Exocyst	0.018	0.045	-9999	-0.31	9	9
AS160/14-3-3	0.025	0.066	-9999	-0.39	1	1
VAMP2	0.017	0.023	-9999	-0.52	1	1
SLC2A4	0.033	0.056	-9999	-0.32	2	2
STX4	0.017	0.023	-9999	-0.52	1	1
GSK3B	0.026	0.032	-9999	-0.31	4	4
SFN	-0.015	0.12	-9999	-0.45	37	37
LNPEP	0.01	0.06	-9999	-0.43	9	9
YWHAE	0.016	0.029	-9999	-0.34	3	3

×

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	0.033	0.064	-10000	0	-0.29	16	16
Ran/GTP/Exportin 1/HDAC1	-0.001	0.011	-10000	0	-0.22	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.039	0.064	-10000	0	-0.27	14	14
SUMO1	0.018	0	-10000	0	-10000	0	0
ZFPM1	0.009	0.068	-10000	0	-0.47	10	10
NPC/RanGAP1/SUMO1/Ubc9	0.023	0.013	-10000	0	-0.2	1	1
FKBP3	0.013	0.048	-10000	0	-0.47	5	5
Histones	0.043	0.05	-10000	0	-0.28	2	2
YY1/LSF	0.02	0.056	-10000	0	-0.26	20	20
SMG5	0.016	0.029	-10000	0	-0.34	3	3
RAN	0.017	0.012	-10000	0	-0.25	1	1
I kappa B alpha/HDAC3	0.025	0.056	-10000	0	-0.24	19	19
I kappa B alpha/HDAC1	0.027	0.051	-10000	0	-0.31	6	6
SAP18	0.018	0	-10000	0	-10000	0	0
RELA	0.03	0.051	-10000	0	-10000	0	0
HDAC1/Smad7	0.035	0.022	-10000	0	-0.3	2	2
RANGAP1	0.014	0.037	-10000	0	-0.29	7	7
HDAC3/TR2	0.026	0.053	-10000	0	-0.28	9	9
NuRD/MBD3 Complex	0.045	0.038	-10000	0	-0.33	1	1
NF kappa B1 p50/RelA	0.035	0.049	-10000	0	-0.24	1	1
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.007	0.093	-10000	0	-0.31	40	40
GATA1	0.018	0	-10000	0	-10000	0	0
Mad/Max	0.024	0.021	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.053	0.054	-10000	0	-0.48	2	2
RBBP7	0.01	0.051	-10000	0	-0.3	13	13
NPC	0.01	0.008	-10000	0	-10000	0	0
RBBP4	0.016	0.026	-10000	0	-0.39	2	2
MAX	0.018	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.015	0.035	-10000	0	-0.43	3	3
NFKBIA	0.02	0.054	-10000	0	-0.36	5	5
KAT2B	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.041	0.036	-10000	0	-10000	0	0
SIN3 complex	0.042	0.032	-10000	0	-0.27	5	5
SMURF1	0.018	0	-10000	0	-10000	0	0
CHD3	0.015	0.037	-10000	0	-0.39	4	4
SAP30	0.012	0.053	-10000	0	-0.48	6	6
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.016	0.033	-10000	0	-0.52	2	2
YY1/HDAC3	0.032	0.046	-10000	0	-0.29	2	2
YY1/HDAC2	0.022	0.045	-10000	0	-0.25	11	11
YY1/HDAC1	0.027	0.036	-10000	0	-0.23	10	10
NuRD/MBD2 Complex (MeCP1)	0.044	0.038	-10000	0	-0.33	1	1
PPARG	0.006	0.096	-10000	0	-0.3	38	38
HDAC8/hEST1B	0.034	0.027	-10000	0	-0.3	3	3
UBE2I	0.018	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.015	0.035	-10000	0	-0.43	3	3
TNFRSF1A	0.016	0.033	-10000	0	-0.52	2	2
HDAC3/SMRT (N-CoR2)	0.03	0.041	-10000	0	-0.32	2	2
MBD3L2	0.007	0.072	-10000	0	-0.45	12	12
ubiquitin-dependent protein catabolic process	0.034	0.022	-10000	0	-0.3	2	2
CREBBP	0.016	0.033	-10000	0	-0.52	2	2
NuRD/MBD3/MBD3L2 Complex	0.049	0.051	-10000	0	-0.32	2	2
HDAC1	0.017	0.023	-10000	0	-0.52	1	1
HDAC3	0.023	0.045	-10000	0	-0.36	2	2
HDAC2	0.009	0.053	-10000	0	-0.29	15	15
YY1	0.021	0.038	-10000	0	-0.27	9	9
HDAC8	0.016	0.033	-10000	0	-0.52	2	2
SMAD7	0.016	0.026	-10000	0	-0.39	2	2
NCOR2	0.018	0	-10000	0	-10000	0	0
MXD1	0.014	0.031	-10000	0	-0.25	7	7
STAT3	0.024	0.044	-10000	0	-0.31	9	9
NFKB1	0.017	0.023	-10000	0	-0.52	1	1
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.017	0.017	-10000	0	-0.25	2	2
YY1/LSF/HDAC1	0.03	0.054	-10000	0	-0.23	21	21
YY1/SAP30/HDAC1	0.033	0.047	-10000	0	-0.24	14	14
EP300	0.014	0.047	-10000	0	-0.52	4	4
STAT3 (dimer non-phopshorylated)	0.024	0.044	-10000	0	-0.31	9	9
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.054	-10000	0	-0.36	5	5
histone deacetylation	0.044	0.038	-10000	0	-0.32	1	1
STAT3 (dimer non-phopshorylated)/HDAC3	0.035	0.051	-10000	0	-0.32	3	3
nuclear export	-0.033	0.027	0.3	3	-10000	0	3
PRKACA	0.018	0	-10000	0	-10000	0	0
GATAD2B	0.017	0.023	-10000	0	-0.52	1	1
GATAD2A	0.014	0.037	-10000	0	-0.29	7	7
GATA2/HDAC3	0.017	0.069	-10000	0	-0.32	12	12
GATA1/HDAC1	0.026	0.017	-10000	0	-0.37	1	1
GATA1/HDAC3	0.03	0.041	-10000	0	-0.32	2	2
CHD4	0.017	0.023	-10000	0	-0.52	1	1
TNF-alpha/TNFR1A	0.009	0.071	-10000	0	-0.37	14	14
SIN3/HDAC complex/Mad/Max	0.046	0.033	-10000	0	-0.22	1	1
NuRD Complex	0.052	0.044	-10000	0	-0.32	2	2
positive regulation of chromatin silencing	0.04	0.049	-10000	0	-0.27	2	2
SIN3B	0.017	0.012	-10000	0	-0.25	1	1
MTA2	0.014	0.044	-10000	0	-0.41	5	5
SIN3A	0.018	0	-10000	0	-10000	0	0
XPO1	0.018	0	-10000	0	-10000	0	0
SUMO1/HDAC1	0.036	0.018	-10000	0	-0.24	1	1
HDAC complex	0.035	0.045	-10000	0	-0.26	7	7
GATA1/Fog1	0.02	0.049	-10000	0	-0.37	8	8
FKBP25/HDAC1/HDAC2	0.027	0.047	-10000	0	-0.3	8	8
TNF	-0.004	0.094	-10000	0	-0.36	31	31
negative regulation of cell growth	0.046	0.033	-10000	0	-0.22	1	1
NuRD/MBD2/PRMT5 Complex	0.044	0.038	-10000	0	-0.33	1	1
Ran/GTP/Exportin 1	0.039	0.013	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.031	0.065	-10000	0	-0.29	16	16
SIN3/HDAC complex/NCoR1	0.043	0.035	-10000	0	-10000	0	0
TFCP2	0.006	0.077	-10000	0	-0.52	11	11
NR2C1	0.011	0.062	-10000	0	-0.52	7	7
MBD3	0.018	0	-10000	0	-10000	0	0
MBD2	0.017	0.017	-10000	0	-0.25	2	2

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	0.024	0.045	-10000	0	-0.29	8	8
MAPK9	-0.005	0.07	-10000	0	-0.33	23	23
adrenocorticotropin secretion	0.005	0.042	-10000	0	-0.2	18	18
GNB1/GNG2	0.02	0.037	-10000	0	-0.31	6	6
GNB1	0.013	0.052	-10000	0	-0.52	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	0.01	0.005	-10000	0	-10000	0	0
Gs family/GTP	0.008	0.028	-10000	0	-0.17	11	11
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	0.001	0.007	0.048	11	-10000	0	11
GNAL	0.011	0.052	-10000	0	-0.33	11	11
GNG2	0.016	0.029	-10000	0	-0.34	3	3
CRH	0.007	0.06	-10000	0	-0.3	18	18
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.008	0.026	-10000	0	-0.33	3	3
MAPK11	0.01	0	-10000	0	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.023	0.017	-10000	0	-0.2	2	2
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.02	0.019	-10000	0	-0.27	1	1
AP2	0.021	0.04	-10000	0	-0.36	5	5
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.019	0.041	-10000	0	-0.31	8	8
CLTB	0.015	0.035	-10000	0	-0.43	3	3
coatomer protein complex/ARF1/GTP/ER cargo protein	0.027	0.02	-10000	0	-0.24	3	3
CD4	0.018	0	-10000	0	-10000	0	0
CLTA	0.018	0	-10000	0	-10000	0	0
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
ARFGAP1	0.012	0.011	-10000	0	-0.17	2	2
mol:PI-4-5-P2	0.012	0.025	0.15	8	-0.18	4	12
ARF1/GTP	-0.001	0.015	-10000	0	-0.29	1	1
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.028	0.014	-10000	0	-0.2	1	1
mol:Choline	0.011	0.025	0.15	8	-0.19	4	12
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.016	0.024	-10000	0	-0.53	1	1
DDEF1	0.012	0.025	0.15	8	-0.19	4	12
ARF1/GDP	0.009	0.012	-10000	0	-0.11	2	2
AP2M1	0.013	0.049	-10000	0	-0.43	6	6
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.017	0.013	-10000	0	-0.28	1	1
Rac/GTP	0.014	0.001	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.028	0.02	-10000	0	-0.26	2	2
ARFIP2	0.008	0.063	-10000	0	-0.47	9	9
COPA	0.018	0	-10000	0	-10000	0	0
RAC1	0.018	0	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.026	0.017	-10000	0	-0.2	2	2
ARF1/GTP/ARHGAP10	0.01	0.014	-10000	0	-0.32	1	1
GGA3	0.016	0.026	-10000	0	-0.39	2	2
ARF1/GTP/Membrin	0.017	0.015	-10000	0	-0.27	1	1
AP2A1	0.016	0.024	-10000	0	-0.25	4	4
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.028	0.021	-10000	0	-0.23	3	3
ARF1/GDP/Membrin	0.019	0.015	-10000	0	-0.26	1	1
Arfaptin 2/Rac/GDP	0.018	0.041	-10000	0	-0.31	8	8
CYTH2	0.001	0.002	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.021	0.022	-10000	0	-0.32	2	2
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.013	0	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.036	0.036	-10000	0	-0.45	2	2
PLD2	0.011	0.026	0.15	8	-0.19	4	12
ARF-GAP1/v-SNARE	0.012	0.011	-10000	0	-0.17	2	2
PIP5K1A	0.012	0.025	0.15	8	-0.18	4	12
ARF1/GTP/Membrin/GBF1/p115	0.018	0.016	-10000	0	-0.26	1	1
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.011	0.025	0.15	8	-0.19	4	12
KDEL Receptor/Ligand/ARF-GAP1	0.012	0.011	-10000	0	-0.17	2	2
GOSR2	0.015	0.014	-10000	0	-10000	0	0
USO1	0.015	0.013	-10000	0	-10000	0	0
GBF1	0.014	0.023	-10000	0	-0.41	1	1
ARF1/GTP/Arfaptin 2	0.018	0.044	-10000	0	-0.31	9	9
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.032	0.035	-10000	0	-0.3	5	5

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.017	0.023	-9999	-0.52	1	1
Ran/GTP/Exportin 1/HDAC4	-0.001	0.012	-9999	-0.25	1	1
MDM2/SUMO1	0.033	0.024	-9999	-10000	0	0
HDAC4	0.017	0.023	-9999	-0.52	1	1
Ran/GTP/Exportin 1/HDAC1	-0.001	0.011	-9999	-0.2	1	1
SUMO1	0.018	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.018	0.015	-9999	-0.24	1	1
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.029	0.013	-9999	-0.18	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.017	0.012	-9999	-0.25	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.017	0.017	-9999	-0.25	2	2
SUMO1/HDAC4	0.036	0.019	-9999	-0.31	1	1
SUMO1/HDAC1	0.036	0.018	-9999	-0.24	1	1
RANGAP1	0.014	0.037	-9999	-0.29	7	7
MDM2/SUMO1/SUMO1	0.04	0.031	-9999	-0.27	2	2
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.023	0.013	-9999	-0.2	1	1
Ran/GTP	0.031	0.013	-9999	-0.18	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.011	0.044	-9999	-0.25	14	14
UBE2I	0.018	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.037	0.013	-9999	-10000	0	0
NPC	0.01	0.008	-9999	-10000	0	0
PIAS2	0.015	0.035	-9999	-0.43	3	3
PIAS1	0.017	0.012	-9999	-0.25	1	1
EntrezGene:9972	0	0	-9999	-10000	0	0