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)	114
Signaling events regulated by Ret tyrosine kinase	111
FOXM1 transcription factor network	86
Wnt signaling	83
EGFR-dependent Endothelin signaling events	83
IGF1 pathway	83
Endothelins	82
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	79
HIF-1-alpha transcription factor network	77
Plasma membrane estrogen receptor signaling	75

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)	114	8909	78	-0.39	0.17	1000	-1000	-0.037	-1000
Signaling events regulated by Ret tyrosine kinase	111	9126	82	-0.23	0.018	1000	-1000	-0.06	-1000
FOXM1 transcription factor network	86	4424	51	-0.43	0.024	1000	-1000	-0.12	-1000
Wnt signaling	83	584	7	-0.13	-0.011	1000	-1000	-0.012	-1000
EGFR-dependent Endothelin signaling events	83	1747	21	-0.17	0.024	1000	-1000	-0.049	-1000
IGF1 pathway	83	4786	57	-0.14	0.058	1000	-1000	-0.059	-1000
Endothelins	82	7963	96	-0.24	0.018	1000	-1000	-0.044	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	79	5392	68	-0.43	0.22	1000	-1000	-0.072	-1000
HIF-1-alpha transcription factor network	77	5888	76	-0.26	0.025	1000	-1000	-0.048	-1000
Plasma membrane estrogen receptor signaling	75	6487	86	-0.2	0.19	1000	-1000	-0.056	-1000
Syndecan-1-mediated signaling events	74	2533	34	-0.19	0.018	1000	-1000	-0.027	-1000
TCGA08_retinoblastoma	69	558	8	-0.053	0.026	1000	-1000	-0.006	-1000
FAS signaling pathway (CD95)	68	3222	47	-0.16	0.072	1000	-1000	-0.026	-1000
IL6-mediated signaling events	68	5146	75	-0.18	0.043	1000	-1000	-0.035	-1000
Glucocorticoid receptor regulatory network	67	7743	114	-0.55	0.28	1000	-1000	-0.051	-1000
IL4-mediated signaling events	66	6070	91	-0.51	0.39	1000	-1000	-0.12	-1000
TCR signaling in naïve CD8+ T cells	66	6187	93	-0.13	0.071	1000	-1000	-0.046	-1000
IL12-mediated signaling events	62	5422	87	-0.3	0.029	1000	-1000	-0.083	-1000
IL27-mediated signaling events	62	3181	51	-0.27	0.17	1000	-1000	-0.059	-1000
Fc-epsilon receptor I signaling in mast cells	61	6012	97	-0.15	0.038	1000	-1000	-0.054	-1000
Arf6 signaling events	60	3728	62	-0.15	0.034	1000	-1000	-0.011	-1000
Osteopontin-mediated events	59	2244	38	-0.15	0.018	1000	-1000	-0.021	-1000
Noncanonical Wnt signaling pathway	59	1552	26	-0.13	0.018	1000	-1000	-0.032	-1000
IL23-mediated signaling events	58	3498	60	-0.28	0.017	1000	-1000	-0.096	-1000
Thromboxane A2 receptor signaling	56	5882	105	-0.14	0.038	1000	-1000	-0.046	-1000
Signaling events mediated by the Hedgehog family	53	2776	52	-0.16	0.056	1000	-1000	-0.012	-1000
Nongenotropic Androgen signaling	53	2764	52	-0.13	0.063	1000	-1000	-0.032	-1000
PLK2 and PLK4 events	50	150	3	-0.049	0.008	1000	-1000	-0.011	-1000
E-cadherin signaling events	50	250	5	-0.049	0.011	1000	-1000	-0.007	-1000
BMP receptor signaling	48	3934	81	-0.23	0.046	1000	-1000	-0.067	-1000
Stabilization and expansion of the E-cadherin adherens junction	48	3583	74	-0.14	0.03	1000	-1000	-0.061	-1000
Syndecan-4-mediated signaling events	48	3250	67	-0.079	0.022	1000	-1000	-0.025	-1000
ErbB4 signaling events	45	3155	69	-0.17	0.099	1000	-1000	-0.056	-1000
Ephrin B reverse signaling	42	2020	48	-0.14	0.02	1000	-1000	-0.043	-1000
LPA receptor mediated events	41	4202	102	-0.13	0.018	1000	-1000	-0.05	-1000
amb2 Integrin signaling	39	3253	82	-0.12	0.023	1000	-1000	-0.05	-1000
TCGA08_p53	39	277	7	-0.037	0.029	1000	-1000	-0.007	-1000
Caspase cascade in apoptosis	38	2874	74	-0.086	0.045	1000	-1000	-0.023	-1000
Syndecan-2-mediated signaling events	38	2639	69	-0.073	0.022	1000	-1000	-0.017	-1000
Integrins in angiogenesis	38	3232	84	-0.19	0.031	1000	-1000	-0.053	-1000
BCR signaling pathway	38	3819	99	-0.16	0.043	1000	-1000	-0.06	-1000
Signaling events mediated by PTP1B	37	2832	76	-0.15	0.054	1000	-1000	-0.05	-1000
IL2 signaling events mediated by PI3K	37	2166	58	-0.23	0.018	1000	-1000	-0.056	-1000
Canonical Wnt signaling pathway	37	1887	51	-0.25	0.098	1000	-1000	-0.033	-1000
Visual signal transduction: Rods	37	1962	52	-0.1	0.026	1000	-1000	-0.05	-1000
Calcium signaling in the CD4+ TCR pathway	36	1140	31	-0.14	0.027	1000	-1000	-0.041	-1000
Ras signaling in the CD4+ TCR pathway	35	601	17	-0.037	0.013	1000	-1000	-0.009	-1000
Coregulation of Androgen receptor activity	34	2593	76	-0.19	0.029	1000	-1000	-0.026	-1000
TRAIL signaling pathway	34	1643	48	-0.049	0.018	1000	-1000	-0.042	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	34	1552	45	-0.13	0.018	1000	-1000	-0.056	-1000
Glypican 2 network	34	138	4	-0.016	0	1000	-1000	-0.002	-1000
Cellular roles of Anthrax toxin	33	1299	39	-0.14	0.018	1000	-1000	-0.015	-1000
Glypican 1 network	33	1623	48	-0.064	0.017	1000	-1000	-0.014	-1000
IL1-mediated signaling events	33	2050	62	-0.083	0.051	1000	-1000	-0.05	-1000
Class IB PI3K non-lipid kinase events	33	99	3	-0.004	-1000	1000	-1000	-0.002	-1000
Signaling mediated by p38-gamma and p38-delta	32	483	15	-0.07	0.014	1000	-1000	-0.01	-1000
Presenilin action in Notch and Wnt signaling	31	1929	61	-0.22	0.036	1000	-1000	-0.043	-1000
Nectin adhesion pathway	31	1970	63	-0.11	0.024	1000	-1000	-0.051	-1000
E-cadherin signaling in the nascent adherens junction	31	2428	76	-0.079	0.024	1000	-1000	-0.057	-1000
Regulation of nuclear SMAD2/3 signaling	30	4123	136	-0.2	0.065	1000	-1000	-0.027	-1000
Syndecan-3-mediated signaling events	30	1068	35	-0.099	0.032	1000	-1000	-0.027	-1000
PDGFR-alpha signaling pathway	29	1283	44	-0.18	0.028	1000	-1000	-0.021	-1000
Regulation of Telomerase	29	3000	102	-0.2	0.044	1000	-1000	-0.07	-1000
Visual signal transduction: Cones	28	1091	38	-0.071	0.025	1000	-1000	-0.008	-1000
Class I PI3K signaling events	27	2040	73	-0.089	0.031	1000	-1000	-0.032	-1000
Ceramide signaling pathway	26	2029	76	-0.14	0.055	1000	-1000	-0.015	-1000
Reelin signaling pathway	26	1494	56	-0.09	0.038	1000	-1000	-0.053	-1000
IL2 signaling events mediated by STAT5	26	584	22	-0.072	0.021	1000	-1000	-0.014	-1000
Insulin Pathway	26	1966	74	-0.16	0.05	1000	-1000	-0.06	-1000
E-cadherin signaling in keratinocytes	26	1148	43	-0.077	0.018	1000	-1000	-0.018	-1000
Aurora B signaling	26	1760	67	-0.096	0.02	1000	-1000	-0.04	-1000
p75(NTR)-mediated signaling	25	3138	125	-0.13	0.036	1000	-1000	-0.059	-1000
IFN-gamma pathway	25	1756	68	-0.087	0.023	1000	-1000	-0.059	-1000
Effects of Botulinum toxin	25	674	26	-0.17	0.019	1000	-1000	-0.019	-1000
TCGA08_rtk_signaling	25	652	26	-0.077	0.039	1000	-1000	-0.007	-1000
FOXA2 and FOXA3 transcription factor networks	24	1145	46	-0.2	0.074	1000	-1000	-0.023	-1000
RXR and RAR heterodimerization with other nuclear receptor	24	1273	52	-0.12	0.037	1000	-1000	-0.046	-1000
Sphingosine 1-phosphate (S1P) pathway	23	662	28	-0.081	0.02	1000	-1000	-0.016	-1000
PLK1 signaling events	22	1934	85	-0.1	0.028	1000	-1000	-0.032	-1000
Regulation of Androgen receptor activity	22	1608	70	-0.18	0.026	1000	-1000	-0.03	-1000
S1P1 pathway	21	770	36	-0.062	0.018	1000	-1000	-0.05	-1000
Atypical NF-kappaB pathway	21	667	31	-0.073	0.028	1000	-1000	-0.009	-1000
Angiopoietin receptor Tie2-mediated signaling	21	1849	88	-0.16	0.053	1000	-1000	-0.086	-1000
Arf6 downstream pathway	20	901	43	-0.022	0.019	1000	-1000	-0.026	-1000
HIF-2-alpha transcription factor network	20	883	43	-0.084	0.085	1000	-1000	-0.054	-1000
Aurora A signaling	19	1182	60	-0.037	0.034	1000	-1000	-0.012	-1000
mTOR signaling pathway	19	1054	53	-0.037	0.035	1000	-1000	-0.042	-1000
ceramide signaling pathway	19	935	49	-0.12	0.036	1000	-1000	-0.019	-1000
VEGFR1 specific signals	19	1069	56	-0.034	0.027	1000	-1000	-0.024	-1000
PDGFR-beta signaling pathway	19	1872	97	-0.081	0.036	1000	-1000	-0.05	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	18	984	54	-0.092	0.031	1000	-1000	-0.058	-1000
ErbB2/ErbB3 signaling events	17	1152	65	-0.06	0.024	1000	-1000	-0.046	-1000
JNK signaling in the CD4+ TCR pathway	17	294	17	-0.036	0.029	1000	-1000	-0.019	-1000
Hedgehog signaling events mediated by Gli proteins	17	1121	65	-0.051	0.041	1000	-1000	-0.039	-1000
EPHB forward signaling	17	1496	85	-0.038	0.036	1000	-1000	-0.06	-1000
Regulation of p38-alpha and p38-beta	17	947	54	-0.073	0.043	1000	-1000	-0.04	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	17	590	33	-0.074	0.049	1000	-1000	-0.027	-1000
Signaling events mediated by PRL	17	593	34	-0.097	0.026	1000	-1000	-0.011	-1000
p38 MAPK signaling pathway	17	778	44	-0.079	0.034	1000	-1000	-0.053	-1000
BARD1 signaling events	16	944	57	-0.039	0.04	1000	-1000	-0.032	-1000
Signaling events mediated by HDAC Class III	16	670	40	-0.08	0.034	1000	-1000	-0.017	-1000
Retinoic acid receptors-mediated signaling	16	934	58	-0.086	0.039	1000	-1000	-0.057	-1000
Signaling events mediated by VEGFR1 and VEGFR2	16	2007	125	-0.061	0.055	1000	-1000	-0.068	-1000
S1P3 pathway	16	689	42	-0.081	0.02	1000	-1000	-0.024	-1000
Neurotrophic factor-mediated Trk receptor signaling	16	1996	120	-0.12	0.053	1000	-1000	-0.05	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	15	1315	85	-0.14	0.038	1000	-1000	-0.05	-1000
Paxillin-independent events mediated by a4b1 and a4b7	15	563	37	-0.024	0.028	1000	-1000	-0.02	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	15	1264	83	-0.12	0.057	1000	-1000	-0.025	-1000
Signaling mediated by p38-alpha and p38-beta	15	693	44	-0.091	0.024	1000	-1000	-0.023	-1000
EPO signaling pathway	14	798	55	-0.15	0.023	1000	-1000	-0.053	-1000
LPA4-mediated signaling events	13	164	12	-0.029	0.015	1000	-1000	-0.009	-1000
a4b1 and a4b7 Integrin signaling	13	68	5	-0.007	0.018	1000	-1000	-0.005	-1000
Signaling events mediated by HDAC Class II	12	951	75	-0.16	0.039	1000	-1000	-0.028	-1000
Paxillin-dependent events mediated by a4b1	11	421	36	-0.033	0.036	1000	-1000	-0.05	-1000
Aurora C signaling	10	72	7	-0.007	0.015	1000	-1000	-0.027	-1000
Nephrin/Neph1 signaling in the kidney podocyte	9	338	34	-0.01	0.035	1000	-1000	-0.016	-1000
Circadian rhythm pathway	9	198	22	-0.045	0.042	1000	-1000	-0.033	-1000
S1P5 pathway	9	159	17	-0.015	0.018	1000	-1000	-0.015	-1000
FoxO family signaling	9	624	64	-0.12	0.067	1000	-1000	-0.034	-1000
Alternative NF-kappaB pathway	9	117	13	0	0.034	1000	-1000	-0.005	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	8	184	23	-0.031	0.032	1000	-1000	-0.026	-1000
Canonical NF-kappaB pathway	8	347	39	-0.056	0.06	1000	-1000	-0.053	-1000
Ephrin A reverse signaling	8	59	7	0	0.016	1000	-1000	-0.002	-1000
Class I PI3K signaling events mediated by Akt	6	412	68	-0.038	0.053	1000	-1000	-0.023	-1000
S1P4 pathway	6	168	25	-0.015	0.02	1000	-1000	-0.018	-1000
Insulin-mediated glucose transport	5	172	32	-0.015	0.033	1000	-1000	-0.018	-1000
Signaling events mediated by HDAC Class I	5	522	104	-0.033	0.053	1000	-1000	-0.033	-1000
Arf6 trafficking events	5	357	71	-0.021	0.031	1000	-1000	-0.057	-1000
Rapid glucocorticoid signaling	5	118	20	-0.005	0.02	1000	-1000	-0.008	-1000
Arf1 pathway	3	172	54	-0.001	0.036	1000	-1000	-0.014	-1000
Sumoylation by RanBP2 regulates transcriptional repression	1	39	27	-0.001	0.04	1000	-1000	-0.038	-1000
Total	4378	259957	7203	-16	-990	131000	-131000	-4.8	-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	141	141
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	155	155
AKT1	-0.16	0.21	-10000	0	-0.44	163	163
BAD	-0.14	0.2	-10000	0	-0.41	158	158
megakaryocyte differentiation	-0.17	0.23	-10000	0	-0.47	167	167
GSK3B	-0.14	0.2	-10000	0	-0.41	154	154
RAF1	-0.089	0.16	-10000	0	-0.33	92	92
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	-0.9	213	213
HRAS/SPRED1	-0.095	0.17	-10000	0	-0.35	101	101
cell proliferation	-0.17	0.22	-10000	0	-0.45	165	165
PIK3CA	0.015	0.029	-10000	0	-0.35	3	3
TEC	0.013	0.052	-10000	0	-0.52	5	5
RPS6KB1	-0.17	0.22	-10000	0	-0.46	170	170
HRAS/SPRED2	-0.096	0.17	-10000	0	-0.36	91	91
LYN/TEC/p62DOK	-0.15	0.22	-10000	0	-0.45	161	161
MAPK3	-0.054	0.12	-10000	0	-0.26	53	53
STAP1	-0.19	0.24	-10000	0	-0.48	176	176
GRAP2	0.011	0.044	-10000	0	-0.28	11	11
JAK2	-0.31	0.4	-10000	0	-0.75	214	214
STAT1 (dimer)	-0.36	0.47	-10000	0	-0.88	213	213
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	-0.44	182	182
LYN	0.014	0.031	-10000	0	-0.26	7	7
STAP1/STAT5A (dimer)	-0.24	0.31	-10000	0	-0.61	181	181
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
CBL/CRKL/GRB2	-0.13	0.2	-10000	0	-0.41	153	153
PI3K	-0.16	0.23	-10000	0	-0.46	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	153	153
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	-10000	0	-0.21	52	52
mol:GDP	-0.12	0.2	-10000	0	-0.4	147	147
PIK3C2B	-0.17	0.22	-10000	0	-0.47	164	164
CBL/CRKL	-0.14	0.21	-10000	0	-0.42	164	164
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	-10000	0	-0.4	150	150
SNAI2	-0.19	0.25	-10000	0	-0.5	176	176
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	-0.8	3	3
STAT5A (dimer)	-0.23	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	0.46	171	-10000	0	171
SOS1	0.017	0.023	-10000	0	-0.52	1	1
EPO	-0.031	0.1	-10000	0	-0.27	80	80
VAV1	-0.015	0.12	-10000	0	-0.39	42	42
GRB10	-0.18	0.23	-10000	0	-0.48	166	166
PTPN11	0.022	0.024	-10000	0	-0.5	1	1
SCF/KIT	-0.18	0.23	-10000	0	-0.47	182	182
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	-0.26	1	1
KIT	-0.33	0.53	-10000	0	-1.2	122	122
MAP2K2	-0.064	0.13	-10000	0	-0.29	59	59
SHC/Grb2/SOS1	-0.14	0.22	-10000	0	-0.43	159	159
STAT5A	-0.23	0.31	-10000	0	-0.57	213	213
GRB2	0.016	0.024	-10000	0	-0.26	4	4
response to radiation	-0.19	0.24	-10000	0	-0.49	176	176
SHC/GRAP2	0.021	0.035	-10000	0	-0.37	2	2
PTPRO	-0.18	0.23	-10000	0	-0.48	167	167
SH2B2	-0.18	0.22	-10000	0	-0.45	182	182
DOK1	0.002	0.083	-10000	0	-0.41	19	19
MATK	-0.18	0.23	-10000	0	-0.47	171	171
CREBBP	0.004	0.059	-10000	0	-0.54	2	2
BCL2	-0.33	0.55	-10000	0	-1.3	117	117

×

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	0.17	-9999	-0.4	164	164
JUN	-0.17	0.21	-9999	-0.42	172	172
HRAS	0.012	0.051	-9999	-0.41	7	7
RET51/GFRalpha1/GDNF/GRB10	-0.21	0.22	-9999	-0.39	276	276
RAP1A	0.011	0.062	-9999	-0.52	7	7
FRS2	0.01	0.047	-9999	-0.28	13	13
RAP1A/GDP	0.008	0.045	-9999	-0.38	7	7
RET51/GFRalpha1/GDNF/DOK1	-0.21	0.22	-9999	-0.39	270	270
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	246	246
GRB7	-0.017	0.1	-9999	-0.29	59	59
RET51/GFRalpha1/GDNF	-0.2	0.21	-9999	-0.38	264	264
MAPKKK cascade	-0.18	0.19	-9999	-0.45	146	146
BCAR1	0.017	0.012	-9999	-0.26	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	265	265
PIK3CA	0.016	0.029	-9999	-0.35	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	-0.17	0.18	-9999	-0.43	136	136
DOK1	0.002	0.083	-9999	-0.41	19	19
DOK6	-0.027	0.14	-9999	-0.44	51	51
PXN	0.018	0	-9999	-10000	0	0
neurite development	-0.16	0.19	-9999	-0.41	147	147
DOK5	-0.025	0.13	-9999	-0.38	57	57
GFRA1	-0.22	0.24	-9999	-0.43	281	281
MAPK8	-0.16	0.2	-9999	-0.43	146	146
HRAS/GTP	-0.21	0.22	-9999	-0.52	146	146
tube development	-0.091	0.13	-9999	-0.26	193	193
MAPK1	-0.17	0.18	-9999	-0.43	136	136
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	-0.26	1	1
RET51/GFRalpha1/GDNF/Dok6	-0.2	0.23	-9999	-0.4	250	250
SHC1	0.017	0.023	-9999	-0.52	1	1
RET51/GFRalpha1/GDNF/Dok4	-0.2	0.21	-9999	-0.38	268	268
RET51/GFRalpha1/GDNF/Dok5	-0.22	0.23	-9999	-0.41	275	275
PRKCA	0.014	0.034	-9999	-0.26	8	8
HRAS/GDP	0.009	0.037	-9999	-0.29	7	7
CREB1	-0.14	0.19	-9999	-0.44	122	122
PIK3R1	-0.009	0.11	-9999	-0.42	32	32
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	274	274
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	-0.41	172	172
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	0.079	-9999	-0.42	16	16
NCK1	0.011	0.046	-9999	-0.28	12	12
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.077	0.12	-9999	-0.44	4	4
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.16	0.19	-9999	-0.43	134	134
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.17	0.21	-9999	-0.46	144	144
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.18	0.23	-9999	-0.54	132	132
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	0.098	-9999	-0.43	24	24
activation of MAPKK activity	-0.13	0.16	-9999	-0.37	123	123
RET51/GFRalpha1/GDNF/FRS2	-0.2	0.21	-9999	-0.38	267	267
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	137	137
RET51/GFRalpha1/GDNF/PKC alpha	-0.2	0.21	-9999	-0.39	264	264
GRB2	0.016	0.024	-9999	-0.26	4	4
PRKACA	0.018	0	-9999	-10000	0	0
GDNF	0.014	0.042	-9999	-0.46	4	4
RAC1	0.018	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.23	0.26	-9999	-0.44	273	273
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

×

FOXM1 transcription factor network

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
NFATC3	-0.24	0.56	-9999	-1.2	99	99
PLK1	0.024	0.058	-9999	-10000	0	0
BIRC5	-0.092	0.39	-9999	-1.4	40	40
HSPA1B	-0.24	0.56	-9999	-1.1	119	119
MAP2K1	0.018	0.046	-9999	-0.3	1	1
BRCA2	-0.26	0.59	-9999	-1.2	114	114
FOXM1	-0.4	0.93	-9999	-1.8	118	118
XRCC1	-0.24	0.56	-9999	-1.2	98	98
FOXM1B/p19	-0.42	0.55	-9999	-1.2	135	135
Cyclin D1/CDK4	-0.3	0.57	-9999	-1.1	152	152
CDC2	-0.26	0.61	-9999	-1.2	106	106
TGFA	-0.29	0.55	-9999	-1	141	141
SKP2	-0.24	0.57	-9999	-1.2	97	97
CCNE1	-0.019	0.1	-9999	-0.29	64	64
CKS1B	-0.24	0.57	-9999	-1.2	104	104
RB1	-0.22	0.32	-9999	-0.93	67	67
FOXM1C/SP1	-0.3	0.66	-9999	-1.3	123	123
AURKB	0.012	0.13	-9999	-1.4	3	3
CENPF	-0.26	0.6	-9999	-1.2	103	103
CDK4	0.013	0.032	-9999	-0.26	5	5
MYC	-0.22	0.52	-9999	-0.97	129	129
CHEK2	0.011	0.073	-9999	-0.41	9	9
ONECUT1	-0.28	0.57	-9999	-1.1	133	133
CDKN2A	-0.057	0.15	-9999	-0.33	108	108
LAMA4	-0.24	0.57	-9999	-1.2	105	105
FOXM1B/HNF6	-0.37	0.71	-9999	-1.4	133	133
FOS	-0.34	0.64	-9999	-1.2	147	147
SP1	0.016	0.024	-9999	-0.52	1	1
CDC25B	-0.24	0.57	-9999	-1.2	101	101
response to radiation	0	0.039	-9999	-10000	0	0
CENPB	-0.24	0.56	-9999	-1.2	94	94
CENPA	-0.26	0.6	-9999	-1.2	108	108
NEK2	-0.28	0.62	-9999	-1.2	129	129
HIST1H2BA	-0.24	0.57	-9999	-1.1	103	103
CCNA2	-0.025	0.14	-9999	-0.41	53	53
EP300	0.014	0.047	-9999	-0.52	4	4
CCNB1/CDK1	-0.31	0.7	-9999	-1.5	97	97
CCNB2	-0.25	0.58	-9999	-1.2	101	101
CCNB1	-0.27	0.62	-9999	-1.3	108	108
ETV5	-0.25	0.58	-9999	-1.2	110	110
ESR1	-0.43	0.71	-9999	-1.2	214	214
CCND1	-0.31	0.6	-9999	-1.1	153	153
GSK3A	0.019	0.037	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.013	0.13	-9999	-0.35	52	52
CDK2	0.011	0.049	-9999	-0.32	10	10
G2/M transition of mitotic cell cycle	0	0.046	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.37	0.53	-9999	-1.2	124	124
GAS1	-0.32	0.64	-9999	-1.2	148	148
MMP2	-0.27	0.61	-9999	-1.2	115	115
RB1/FOXM1C	-0.3	0.6	-9999	-1.1	144	144
CREBBP	0.016	0.033	-9999	-0.52	2	2

×

Wnt signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.13	0.21	-9999	-0.47	103	103
FZD6	-0.077	0.2	-9999	-0.45	108	108
WNT6	-0.011	0.088	-9999	-0.27	54	54
WNT4	-0.063	0.18	-9999	-0.45	90	90
FZD3	-0.031	0.15	-9999	-0.48	52	52
WNT5A	-0.084	0.2	-9999	-0.43	120	120
WNT11	-0.013	0.09	-9999	-0.27	57	57

×

EGFR-dependent Endothelin 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
HRAS	0.012	0.051	-9999	-0.41	7	7
EGFR	-0.077	0.17	-9999	-0.35	136	136
EGF/EGFR	-0.17	0.21	-9999	-0.36	243	243
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.084	0.16	-9999	-0.29	168	168
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.032	0.15	-9999	-0.5	50	50
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	173	173
mol:GDP	-0.086	0.15	-9999	-0.29	168	168
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.097	0.21	-9999	-0.44	134	134
GRB2/SOS1	0.024	0.024	-9999	-0.37	1	1
HRAS/GTP	-0.1	0.12	-9999	-0.34	59	59
SHC1	0.017	0.023	-9999	-0.52	1	1
HRAS/GDP	-0.08	0.14	-9999	-0.35	59	59
FRAP1	-0.078	0.14	-9999	-0.35	57	57
EGF/EGFR dimer	-0.15	0.2	-9999	-0.42	172	172
SOS1	0.017	0.023	-9999	-0.52	1	1
GRB2	0.016	0.024	-9999	-0.26	4	4
ETA receptor/Endothelin-1	-0.09	0.19	-9999	-0.41	121	121

×

IGF1 pathway

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
NCK2	0.015	0.027	-10000	0	-0.26	5	5
PTK2	0.016	0.029	-10000	0	-0.35	3	3
CRKL	-0.11	0.19	-10000	0	-0.37	155	155
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	-0.37	155	155
IGF-1R heterotetramer/IGF1/PTP1B	-0.11	0.19	-10000	0	-0.37	156	156
AKT1	-0.086	0.18	-10000	0	-0.43	84	84
BAD	-0.075	0.17	-10000	0	-0.4	84	84
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.1	0.19	-10000	0	-0.36	155	155
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.1	0.19	-10000	0	-0.35	170	170
RAF1	-0.064	0.16	-10000	0	-0.4	70	70
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.089	0.19	-10000	0	-0.35	154	154
YWHAZ	0.017	0.017	-10000	0	-0.26	2	2
IGF-1R heterotetramer/IGF1/IRS1	-0.12	0.21	-10000	0	-0.38	170	170
PIK3CA	0.016	0.029	-10000	0	-0.35	3	3
RPS6KB1	-0.087	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	-10000	0	-0.34	70	70
PXN	0.018	0	-10000	0	-10000	0	0
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.024	0.024	-10000	0	-0.37	1	1
HRAS/GTP	-0.1	0.16	-10000	0	-0.43	72	72
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.061	0.16	-10000	0	-0.35	71	71
IGF-1R heterotetramer	-0.11	0.22	-10000	0	-0.51	110	110
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.1	0.2	-10000	0	-0.37	156	156
Crk/p130 Cas/Paxillin	-0.079	0.18	-10000	0	-0.45	72	72
IGF1R	-0.11	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	167	167
PI3K	-0.1	0.2	-10000	0	-0.35	166	166
apoptosis	0.058	0.15	0.34	84	-10000	0	84
HRAS/GDP	0.009	0.037	-10000	0	-0.29	7	7
PRKCD	-0.097	0.21	-10000	0	-0.39	154	154
RAF1/14-3-3 E	-0.048	0.14	-10000	0	-0.34	68	68
BAD/14-3-3	-0.061	0.16	-10000	0	-0.36	84	84
PRKCZ	-0.091	0.18	-10000	0	-0.32	165	165
Crk/p130 Cas/Paxillin/FAK1	-0.088	0.14	-10000	0	-0.39	67	67
PTPN1	0.002	0.071	-10000	0	-0.29	28	28
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.11	0.22	-10000	0	-0.41	154	154
BCAR1	0.017	0.012	-10000	0	-0.26	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.087	0.17	-10000	0	-0.32	164	164
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	153	153
GRB10	-0.003	0.098	-10000	0	-0.43	24	24
PTPN11	-0.1	0.19	-10000	0	-0.35	170	170
IRS1	-0.12	0.2	-10000	0	-0.38	170	170
IRS2	-0.13	0.21	-10000	0	-0.38	170	170
IGF-1R heterotetramer/IGF1	-0.14	0.23	-10000	0	-0.46	157	157
GRB2	0.016	0.024	-10000	0	-0.26	4	4
PDPK1	-0.094	0.19	-10000	0	-0.33	165	165
YWHAE	0.016	0.029	-10000	0	-0.35	3	3
PRKD1	-0.12	0.23	-10000	0	-0.42	156	156
SHC1	0.017	0.023	-10000	0	-0.52	1	1

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.043	0.26	-10000	0	-0.59	60	60
PTK2B	0.017	0.017	-10000	0	-0.26	2	2
mol:Ca2+	-0.072	0.26	-10000	0	-0.67	56	56
EDN1	-0.063	0.24	0.23	56	-0.48	107	163
EDN3	-0.11	0.18	-10000	0	-0.33	194	194
EDN2	-0.13	0.22	-10000	0	-0.41	187	187
HRAS/GDP	-0.11	0.24	-10000	0	-0.46	123	123
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.087	0.22	-10000	0	-0.42	123	123
ADCY4	-0.043	0.22	-10000	0	-0.53	57	57
ADCY5	-0.06	0.22	-10000	0	-0.49	74	74
ADCY6	-0.041	0.21	-10000	0	-0.51	59	59
ADCY7	-0.046	0.22	-10000	0	-0.52	61	61
ADCY1	-0.04	0.21	-10000	0	-0.51	58	58
ADCY2	-0.075	0.24	-10000	0	-0.5	87	87
ADCY3	-0.044	0.21	-10000	0	-0.51	63	63
ADCY8	-0.043	0.21	-10000	0	-0.51	59	59
ADCY9	-0.051	0.22	-10000	0	-0.51	68	68
arachidonic acid secretion	-0.12	0.26	-10000	0	-0.5	130	130
ETB receptor/Endothelin-1/Gq/GTP	-0.08	0.18	-10000	0	-0.35	118	118
GNAO1	0.016	0.024	-10000	0	-0.26	4	4
HRAS	0.011	0.051	-10000	0	-0.41	7	7
ETA receptor/Endothelin-1/G12/GTP	-0.002	0.27	0.36	75	-0.56	57	132
ETA receptor/Endothelin-1/Gs/GTP	-0.006	0.26	0.34	74	-0.54	58	132
mol:GTP	-0.001	0.006	-10000	0	-10000	0	0
COL3A1	-0.047	0.28	-10000	0	-0.67	58	58
EDNRB	-0.031	0.13	-10000	0	-0.39	53	53
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.042	0.26	-10000	0	-0.63	56	56
CYSLTR1	-0.075	0.3	-10000	0	-0.66	81	81
SLC9A1	-0.01	0.15	0.2	20	-0.3	56	76
mol:GDP	-0.12	0.26	-10000	0	-0.48	132	132
SLC9A3	-0.13	0.34	-10000	0	-0.67	125	125
RAF1	-0.13	0.25	-10000	0	-0.48	133	133
JUN	-0.11	0.36	-10000	0	-0.99	60	60
JAK2	-0.043	0.26	0.28	58	-0.54	72	130
mol:IP3	-0.11	0.22	-10000	0	-0.44	123	123
ETA receptor/Endothelin-1	-0.019	0.33	0.42	79	-0.57	86	165
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	-0.082	0.19	-10000	0	-0.41	100	100
FOS	-0.18	0.35	-10000	0	-0.88	89	89
Gai/GDP	-0.007	0.14	-10000	0	-0.81	11	11
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	-0.26	1	1
PRKCB1	-0.13	0.24	-10000	0	-0.46	136	136
GNAQ	-0.001	0.007	-10000	0	-10000	0	0
GNAZ	0.002	0.085	-10000	0	-0.43	18	18
GNAL	0.01	0.052	-10000	0	-0.33	11	11
Gs family/GDP	-0.12	0.21	-10000	0	-0.45	119	119
ETA receptor/Endothelin-1/Gq/GTP	-0.069	0.23	-10000	0	-0.44	108	108
MAPK14	-0.084	0.17	-10000	0	-0.38	94	94
TRPC6	-0.078	0.28	-10000	0	-0.71	56	56
GNAI2	0.006	0.075	-10000	0	-0.48	12	12
GNAI3	0.017	0.023	-10000	0	-0.52	1	1
GNAI1	-0.015	0.12	-10000	0	-0.38	44	44
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.097	0.18	-10000	0	-0.35	132	132
ETB receptor/Endothelin-2	-0.11	0.18	-10000	0	-0.4	137	137
ETB receptor/Endothelin-3	-0.094	0.16	-10000	0	-0.38	95	95
ETB receptor/Endothelin-1	-0.067	0.21	-10000	0	-0.4	120	120
MAPK3	-0.17	0.34	-10000	0	-0.76	106	106
MAPK1	-0.17	0.34	-10000	0	-0.76	105	105
Rac1/GDP	-0.1	0.24	-10000	0	-0.46	122	122
cAMP biosynthetic process	-0.048	0.22	0.27	1	-0.5	71	72
MAPK8	-0.09	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	-0.036	0.16	-10000	0	-0.39	50	50
p130Cas/CRK/Src/PYK2	-0.1	0.25	-10000	0	-0.52	110	110
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.1	0.24	-10000	0	-0.46	122	122
COL1A2	-0.12	0.38	-10000	0	-0.82	98	98
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.099	0.22	-10000	0	-0.4	152	152
mol:DAG	-0.11	0.22	-10000	0	-0.44	123	123
MAP2K2	-0.15	0.28	-10000	0	-0.59	119	119
MAP2K1	-0.15	0.28	-10000	0	-0.6	115	115
EDNRA	-0.003	0.21	-10000	0	-0.57	50	50
positive regulation of muscle contraction	-0.031	0.23	-10000	0	-0.52	60	60
Gq family/GDP	-0.13	0.21	-10000	0	-0.48	106	106
HRAS/GTP	-0.12	0.23	-10000	0	-0.44	132	132
PRKCH	-0.1	0.22	-10000	0	-0.44	116	116
RAC1	0.018	0	-10000	0	-10000	0	0
PRKCA	-0.098	0.22	-10000	0	-0.44	113	113
PRKCB	-0.1	0.21	-10000	0	-0.41	130	130
PRKCE	-0.099	0.22	-10000	0	-0.44	115	115
PRKCD	-0.099	0.22	-10000	0	-0.44	115	115
PRKCG	-0.097	0.22	-10000	0	-0.44	111	111
regulation of vascular smooth muscle contraction	-0.21	0.41	-10000	0	-1.1	87	87
PRKCQ	-0.11	0.23	-10000	0	-0.45	123	123
PLA2G4A	-0.14	0.28	-10000	0	-0.55	130	130
GNA14	-0.083	0.18	-10000	0	-0.36	141	141
GNA15	0	0.079	-10000	0	-0.33	25	25
GNA12	0.018	0	-10000	0	-10000	0	0
GNA11	0.012	0.047	-10000	0	-0.52	4	4
Rac1/GTP	-0.001	0.27	0.36	75	-0.56	56	131
MMP1	-0.24	0.4	0.33	1	-0.89	132	133

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.016	0.037	-10000	0	-0.36	3	3
NFATC2	-0.11	0.26	-10000	0	-0.63	66	66
NFATC3	-0.055	0.11	-10000	0	-0.26	28	28
CD40LG	-0.32	0.43	-10000	0	-0.89	155	155
ITCH	0.006	0.085	-10000	0	-10000	0	0
CBLB	0.004	0.092	-10000	0	-0.6	2	2
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.23	0.38	-10000	0	-0.89	94	94
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	49	49
T cell anergy	-0.033	0.14	-10000	0	-0.39	49	49
TLE4	-0.071	0.23	-10000	0	-0.72	37	37
Jun/NFAT1-c-4/p21SNFT	-0.29	0.45	-10000	0	-0.91	146	146
AP-1/NFAT1-c-4	-0.37	0.52	-10000	0	-1	154	154
IKZF1	-0.079	0.23	-10000	0	-0.72	39	39
T-helper 2 cell differentiation	-0.22	0.35	-10000	0	-0.82	102	102
AP-1/NFAT1	-0.14	0.24	-10000	0	-0.52	108	108
CALM1	0.002	0.058	-10000	0	-10000	0	0
EGR2	-0.29	0.51	-10000	0	-1.1	117	117
EGR3	-0.37	0.58	-10000	0	-1.3	132	132
NFAT1/FOXP3	-0.064	0.2	-10000	0	-0.54	45	45
EGR1	-0.1	0.2	-10000	0	-0.39	155	155
JUN	-0.036	0.15	-10000	0	-0.47	54	54
EGR4	0	0.007	-10000	0	-10000	0	0
mol:Ca2+	-0.016	0.06	-10000	0	-0.17	49	49
GBP3	-0.14	0.31	-10000	0	-0.75	94	94
FOSL1	0.016	0.024	-10000	0	-0.26	4	4
NFAT1-c-4/MAF/IRF4	-0.27	0.44	-10000	0	-0.85	158	158
DGKA	-0.065	0.21	-10000	0	-0.7	32	32
CREM	0.016	0.017	-10000	0	-0.26	2	2
NFAT1-c-4/PPARG	-0.3	0.45	-10000	0	-0.89	161	161
CTLA4	-0.051	0.18	-10000	0	-0.53	41	41
NFAT1-c-4 (dimer)/EGR1	-0.33	0.47	-10000	0	-0.94	164	164
NFAT1-c-4 (dimer)/EGR4	-0.28	0.44	-10000	0	-0.88	157	157
FOS	-0.11	0.2	-10000	0	-0.37	171	171
IFNG	-0.3	0.47	-10000	0	-1.1	98	98
T cell activation	-0.17	0.29	-10000	0	-0.77	58	58
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	0.72	151	-10000	0	151
TNF	-0.29	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	-0.33	51	51
PTPN1	-0.068	0.2	-10000	0	-0.64	36	36
NFAT1-c-4/ICER1	-0.28	0.44	-10000	0	-0.88	155	155
GATA3	-0.1	0.23	-10000	0	-0.51	124	124
T-helper 1 cell differentiation	-0.29	0.44	-10000	0	-1	102	102
IL2RA	-0.25	0.36	-10000	0	-0.83	104	104
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.058	0.19	-10000	0	-0.62	30	30
E2F1	0.013	0.071	-10000	0	-0.37	16	16
PPARG	-0.035	0.13	-10000	0	-0.33	79	79
SLC3A2	-0.059	0.19	-10000	0	-0.61	32	32
IRF4	-0.01	0.086	-10000	0	-0.27	52	52
PTGS2	-0.33	0.44	-10000	0	-0.9	155	155
CSF2	-0.33	0.43	-10000	0	-0.9	155	155
JunB/Fra1/NFAT1-c-4	-0.25	0.43	-10000	0	-0.83	156	156
IL4	-0.24	0.37	-10000	0	-0.88	98	98
IL5	-0.32	0.43	-10000	0	-0.89	151	151
IL2	-0.18	0.29	-10000	0	-0.79	56	56
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	151	151
CDK4	0.14	0.22	0.59	39	-10000	0	39
PTPRK	-0.12	0.3	-10000	0	-0.76	79	79
IL8	-0.36	0.44	-10000	0	-0.93	157	157
POU2F1	0.027	0	-10000	0	-10000	0	0

×

HIF-1-alpha transcription factor network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.16	0.47	-9999	-0.92	102	102
HDAC7	0.001	0.006	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.13	0.39	-9999	-0.78	88	88
SMAD4	0.01	0.067	-9999	-0.49	9	9
ID2	-0.16	0.48	-9999	-0.93	104	104
AP1	-0.1	0.19	-9999	-0.43	107	107
ABCG2	-0.16	0.48	-9999	-0.94	101	101
HIF1A	-0.055	0.19	-9999	-0.53	58	58
TFF3	-0.23	0.52	-9999	-0.97	131	131
GATA2	-0.013	0.096	-9999	-0.33	40	40
AKT1	-0.007	0.1	-9999	-0.45	8	8
response to hypoxia	-0.02	0.083	-9999	-0.18	10	10
MCL1	-0.16	0.47	-9999	-0.94	97	97
NDRG1	-0.17	0.48	-9999	-0.98	98	98
SERPINE1	-0.17	0.48	-9999	-0.94	105	105
FECH	-0.16	0.48	-9999	-0.92	107	107
FURIN	-0.16	0.48	-9999	-0.92	106	106
NCOA2	0.009	0.063	-9999	-0.4	11	11
EP300	0.008	0.12	-9999	-0.38	12	12
HMOX1	-0.17	0.49	-9999	-0.95	104	104
BHLHE40	-0.17	0.46	-9999	-0.9	108	108
BHLHE41	-0.17	0.46	-9999	-0.9	108	108
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.009	0.16	-9999	-0.36	49	49
ENG	0.007	0.15	-9999	-0.35	43	43
JUN	-0.037	0.16	-9999	-0.47	57	57
RORA	-0.17	0.48	-9999	-0.92	112	112
ABCB1	-0.099	0.25	-9999	-1	29	29
TFRC	-0.18	0.49	-9999	-0.94	111	111
CXCR4	-0.18	0.49	-9999	-0.95	109	109
TF	-0.16	0.47	-9999	-0.95	96	96
CITED2	-0.16	0.48	-9999	-0.93	103	103
HIF1A/ARNT	-0.2	0.54	-9999	-1.1	93	93
LDHA	-0.043	0.15	-9999	-1.2	8	8
ETS1	-0.16	0.48	-9999	-0.94	99	99
PGK1	-0.16	0.47	-9999	-0.92	102	102
NOS2	-0.17	0.46	-9999	-0.9	108	108
ITGB2	-0.17	0.49	-9999	-0.94	109	109
ALDOA	-0.16	0.47	-9999	-0.93	103	103
Cbp/p300/CITED2	-0.16	0.48	-9999	-0.98	92	92
FOS	-0.11	0.2	-9999	-0.38	171	171
HK2	-0.16	0.47	-9999	-0.92	104	104
SP1	0.022	0.031	-9999	-0.52	1	1
GCK	0.01	0.2	-9999	-1	6	6
HK1	-0.16	0.47	-9999	-0.92	102	102
NPM1	-0.16	0.47	-9999	-0.92	103	103
EGLN1	-0.16	0.48	-9999	-0.92	106	106
CREB1	0.025	0.024	-9999	-0.52	1	1
PGM1	-0.16	0.48	-9999	-0.95	100	100
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	-0.92	102	102
VEGFA	-0.087	0.36	-9999	-0.7	84	84
HIF1A/JAB1	-0.038	0.14	-9999	-0.38	62	62
CP	-0.26	0.5	-9999	-0.95	134	134
CXCL12	-0.18	0.51	-9999	-0.98	110	110
COPS5	0.009	0.056	-9999	-0.36	11	11
SMAD3/SMAD4	0.013	0.074	-9999	-0.36	18	18
BNIP3	-0.17	0.48	-9999	-0.93	104	104
EGLN3	-0.2	0.5	-9999	-0.98	110	110
CA9	-0.17	0.48	-9999	-0.94	106	106
TERT	-0.16	0.47	-9999	-0.93	101	101
ENO1	-0.16	0.47	-9999	-0.92	105	105
PFKL	-0.16	0.47	-9999	-0.93	102	102
NCOA1	0.011	0.057	-9999	-0.52	6	6
ADM	-0.2	0.51	-9999	-0.95	122	122
ARNT	0.003	0.076	-9999	-10000	0	0
HNF4A	0.02	0.034	-9999	-0.52	2	2
ADFP	-0.17	0.49	-9999	-0.96	105	105
SLC2A1	-0.086	0.36	-9999	-0.7	84	84
LEP	-0.19	0.48	-9999	-0.91	116	116
HIF1A/ARNT/Cbp/p300	-0.14	0.4	-9999	-0.8	86	86
EPO	-0.094	0.35	-9999	-0.71	69	69
CREBBP	0.01	0.12	-9999	-0.36	10	10
HIF1A/ARNT/Cbp/p300/HDAC7	-0.14	0.39	-9999	-0.79	86	86
PFKFB3	-0.16	0.48	-9999	-0.93	105	105
NT5E	-0.16	0.48	-9999	-0.94	100	100

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.058	0.13	-10000	0	-0.26	153	153
ER alpha/Gai/GDP/Gbeta gamma	-0.089	0.19	-10000	0	-0.35	155	155
AKT1	-0.2	0.35	-10000	0	-0.73	153	153
PIK3CA	0.016	0.029	-10000	0	-0.35	3	3
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.2	0.35	-10000	0	-0.74	153	153
mol:Ca2+	-0.11	0.18	-10000	0	-0.39	115	115
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	153	-10000	0	153
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	0.042	0.12	0.29	41	-10000	0	41
E2/ERA-ERB (dimer)	-0.087	0.15	-10000	0	-0.31	149	149
KRAS	0.008	0.069	-10000	0	-0.45	11	11
G13/GTP	-0.082	0.14	-10000	0	-0.29	151	151
pseudopodium formation	-0.042	0.12	-10000	0	-0.29	41	41
E2/ER alpha (dimer)/PELP1	-0.086	0.15	-10000	0	-0.31	149	149
GRB2	0.016	0.024	-10000	0	-0.26	4	4
GNG2	0.016	0.029	-10000	0	-0.35	3	3
GNAO1	0.016	0.024	-10000	0	-0.26	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	-0.38	151	151
mol:NADP	-0.11	0.22	-10000	0	-0.44	152	152
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
mol:IP3	-0.11	0.19	-10000	0	-0.41	115	115
IGF-1R heterotetramer	-0.083	0.2	-10000	0	-0.47	110	110
PLCB1	-0.12	0.19	-10000	0	-0.42	114	114
PLCB2	-0.075	0.17	-10000	0	-0.5	60	60
IGF1	-0.1	0.21	-10000	0	-0.42	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	0.13	-10000	0	-0.75	11	11
JNK cascade	0.013	0.008	-10000	0	-0.17	1	1
BCAR1	0.017	0.012	-10000	0	-0.26	1	1
ESR2	0.017	0.012	-10000	0	-0.26	1	1
GNAQ	0	0	-10000	0	-10000	0	0
ESR1	-0.16	0.24	-10000	0	-0.45	202	202
Gq family/GDP/Gbeta gamma	-0.025	0.12	-10000	0	-0.5	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	0.002	0.085	-10000	0	-0.43	18	18
E2/ER alpha (dimer)	-0.12	0.17	-10000	0	-0.32	202	202
STRN	0.011	0.056	-10000	0	-0.42	8	8
GNAL	0.01	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	0.017	0.023	-10000	0	-0.52	1	1
GNAI1	-0.015	0.12	-10000	0	-0.38	44	44
HBEGF	-0.091	0.19	-10000	0	-0.43	63	63
cAMP biosynthetic process	-0.082	0.11	-10000	0	-0.25	151	151
SRC	-0.078	0.18	-10000	0	-0.33	156	156
PI3K	0.006	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	-0.34	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	171	171
Gs family/GTP	-0.067	0.13	-10000	0	-0.26	151	151
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	153	153
mol:DAG	-0.11	0.19	-10000	0	-0.41	115	115
Gs family/GDP/Gbeta gamma	-0.1	0.15	-10000	0	-0.32	152	152
MSN	-0.046	0.13	-10000	0	-0.32	41	41
Gq family/GTP	-0.086	0.18	-10000	0	-0.47	72	72
mol:PI-3-4-5-P3	-0.19	0.34	-10000	0	-0.71	153	153
NRAS	0.006	0.072	-10000	0	-0.4	15	15
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.1	0.22	0.42	153	-10000	0	153
GRB2/SOS1	0.024	0.024	-10000	0	-0.37	1	1
RhoA/GDP	-0.094	0.18	-10000	0	-0.37	150	150
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	154	154
ruffle organization	-0.042	0.12	-10000	0	-0.29	41	41
ROCK2	-0.053	0.13	-10000	0	-0.37	29	29
GNA14	-0.081	0.18	-10000	0	-0.35	141	141
GNA15	0.001	0.078	-10000	0	-0.33	25	25
GNA13	0.009	0.059	-10000	0	-0.38	11	11
MMP9	-0.095	0.18	-10000	0	-0.45	47	47
MMP2	-0.088	0.2	-10000	0	-0.46	57	57

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.017	0.023	-9999	-0.52	1	1
CCL5	-0.05	0.18	-9999	-0.49	70	70
SDCBP	0.003	0.081	-9999	-0.4	19	19
FGFR/FGF2/Syndecan-1	-0.17	0.27	-9999	-0.58	116	116
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	-0.58	111	111
Syndecan-1/Syntenin	-0.16	0.26	-9999	-0.59	108	108
MAPK3	-0.13	0.24	-9999	-0.56	94	94
HGF/MET	0.006	0.075	-9999	-0.38	14	14
TGFB1/TGF beta receptor Type II	0.017	0.023	-9999	-0.52	1	1
BSG	0.016	0.024	-9999	-0.26	4	4
keratinocyte migration	-0.15	0.25	-9999	-0.57	111	111
Syndecan-1/RANTES	-0.18	0.28	-9999	-0.61	122	122
Syndecan-1/CD147	-0.14	0.25	-9999	-0.58	102	102
Syndecan-1/Syntenin/PIP2	-0.15	0.25	-9999	-0.57	108	108
LAMA5	0.005	0.075	-9999	-0.42	15	15
positive regulation of cell-cell adhesion	-0.15	0.24	-9999	-0.55	108	108
MMP7	-0.094	0.21	-9999	-0.44	128	128
HGF	0.008	0.069	-9999	-0.45	11	11
Syndecan-1/CASK	-0.16	0.26	-9999	-0.56	116	116
Syndecan-1/HGF/MET	-0.15	0.25	-9999	-0.56	110	110
regulation of cell adhesion	-0.12	0.23	-9999	-0.53	96	96
HPSE	-0.017	0.12	-9999	-0.4	44	44
positive regulation of cell migration	-0.17	0.27	-9999	-0.58	116	116
SDC1	-0.17	0.27	-9999	-0.59	116	116
Syndecan-1/Collagen	-0.17	0.27	-9999	-0.58	116	116
PPIB	0.014	0.044	-9999	-0.42	5	5
MET	-0.001	0.078	-9999	-0.3	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	-0.56	96	96
homophilic cell adhesion	-0.16	0.26	-9999	-0.58	116	116
MMP1	-0.19	0.22	-9999	-0.39	268	268

×

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	45	45
CDKN2C	0.005	0.085	-10000	0	-0.37	23	23
CDKN2A	-0.053	0.15	-10000	0	-0.33	107	107
CCND2	0.019	0.084	0.2	74	-0.15	6	80
RB1	-0.022	0.092	0.15	3	-0.22	76	79
CDK4	0.026	0.095	0.23	77	-10000	0	77
CDK6	0.019	0.093	0.24	61	-0.19	7	68
G1/S progression	0.022	0.092	0.22	76	-0.15	3	79

×

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	0.066	0.099	0.24	117	-10000	0	117
RFC1	0.067	0.099	0.24	121	-10000	0	121
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	-10000	0	-0.68	14	14
FASLG/FAS/FADD/FAF1	-0.013	0.13	0.22	49	-0.3	47	96
MAP2K4	-0.045	0.16	-10000	0	-0.42	45	45
mol:ceramide	-0.044	0.14	-10000	0	-0.38	58	58
GSN	0.055	0.11	0.24	122	-0.3	12	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	50	50
BID	0.011	0.065	0.29	15	-0.32	8	23
MAP3K1	-0.017	0.13	0.26	2	-0.37	30	32
MAP3K7	0.015	0.021	-10000	0	-0.26	3	3
RB1	0.054	0.11	0.24	114	-0.29	9	123
CFLAR	0.011	0.064	-10000	0	-0.46	9	9
HGF/MET	-0.036	0.14	-10000	0	-0.32	91	91
ARHGDIB	0.044	0.12	0.24	109	-0.29	20	129
FADD	-0.002	0.068	-10000	0	-0.26	34	34
actin filament polymerization	-0.055	0.11	0.3	12	-0.24	122	134
NFKB1	-0.043	0.08	-10000	0	-0.3	14	14
MAPK8	-0.061	0.19	-10000	0	-0.46	72	72
DFFA	0.066	0.098	0.24	116	-10000	0	116
DNA fragmentation during apoptosis	0.066	0.098	0.24	122	-10000	0	122
FAS/FADD/MET	-0.014	0.1	-10000	0	-0.32	39	39
CFLAR/RIP1	0.021	0.05	-10000	0	-0.36	8	8
FAIM3	0	0.096	-10000	0	-0.49	19	19
FAF1	0.013	0.025	-10000	0	-0.52	1	1
PARP1	0.064	0.1	0.24	121	-0.28	5	126
DFFB	0.066	0.098	0.24	122	-10000	0	122
CHUK	-0.026	0.092	-10000	0	-0.33	15	15
FASLG	-0.066	0.17	-10000	0	-0.38	107	107
FAS/FADD	-0.019	0.11	-10000	0	-0.38	32	32
HGF	0.008	0.069	-10000	0	-0.45	11	11
LMNA	0.06	0.095	0.22	112	-0.26	7	119
CASP6	0.062	0.1	0.23	122	-0.27	4	126
CASP10	0.012	0.03	-10000	0	-0.26	6	6
CASP3	0.072	0.12	0.28	127	-10000	0	127
PTPN13	-0.071	0.2	-10000	0	-0.49	93	93
CASP8	0.012	0.066	0.37	17	-10000	0	17
IL6	-0.16	0.4	-10000	0	-1.2	60	60
MET	-0.001	0.078	-10000	0	-0.3	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	58	58
activation of caspase activity by cytochrome c	0.011	0.065	0.29	15	-0.32	8	23
PAK2	0.067	0.098	0.24	121	-10000	0	121
BCL2	-0.12	0.22	-10000	0	-0.47	145	145

×

IL6-mediated signaling events

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
BCL2L1	-0.11	0.3	-10000	0	-0.7	64	64
CRP	-0.11	0.3	-10000	0	-0.73	52	52
cell cycle arrest	-0.14	0.34	-10000	0	-0.73	97	97
TIMP1	-0.11	0.3	-10000	0	-0.74	66	66
IL6ST	-0.11	0.22	-10000	0	-0.46	143	143
Rac1/GDP	-0.11	0.22	0.28	1	-0.45	115	116
AP1	-0.05	0.16	-10000	0	-0.45	33	33
GAB2	0.011	0.047	-10000	0	-0.26	16	16
TNFSF11	-0.18	0.41	-10000	0	-0.93	97	97
HSP90B1	0.007	0.11	-10000	0	-0.74	7	7
GAB1	0.007	0.074	-10000	0	-0.42	14	14
MAPK14	-0.11	0.22	-10000	0	-0.51	77	77
AKT1	0.038	0.073	-10000	0	-0.57	2	2
FOXO1	0.036	0.085	-10000	0	-0.5	4	4
MAP2K6	-0.12	0.22	0.27	1	-0.43	133	134
mol:GTP	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.11	0.25	-10000	0	-0.49	110	110
MITF	-0.11	0.22	0.29	1	-0.43	121	122
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	-0.045	0.28	-10000	0	-1.4	23	23
CEBPB	0.013	0.073	-10000	0	-0.34	20	20
GRB2/SOS1/GAB family/SHP2	-0.018	0.1	-10000	0	-0.41	9	9
STAT3	-0.15	0.37	-10000	0	-0.78	97	97
STAT1	-0.042	0.17	-10000	0	-0.95	16	16
CEBPD	-0.16	0.39	-10000	0	-0.91	83	83
PIK3CA	0.017	0.029	-10000	0	-0.34	3	3
PI3K	0.009	0.083	-10000	0	-0.37	21	21
JUN	-0.034	0.15	-10000	0	-0.46	57	57
PIAS3/MITF	-0.097	0.21	0.27	1	-0.44	101	102
MAPK11	-0.11	0.22	-10000	0	-0.51	77	77
STAT3 (dimer)/FOXO1	-0.085	0.29	-10000	0	-0.62	78	78
GRB2/SOS1/GAB family	-0.11	0.18	-10000	0	-0.47	72	72
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.13	0.22	-10000	0	-0.41	149	149
GRB2	0.017	0.024	-10000	0	-0.26	4	4
JAK2	0.01	0.054	-10000	0	-0.32	12	12
LBP	-0.1	0.26	-10000	0	-0.59	60	60
PIK3R1	-0.008	0.11	-10000	0	-0.42	32	32
JAK1	0.013	0.058	-10000	0	-0.53	6	6
MYC	-0.15	0.37	-10000	0	-0.85	84	84
FGG	-0.11	0.3	-10000	0	-0.71	62	62
macrophage differentiation	-0.14	0.34	-10000	0	-0.73	97	97
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.13	0.2	-10000	0	-0.34	215	215
JUNB	-0.11	0.29	-10000	0	-0.66	72	72
FOS	-0.11	0.2	-10000	0	-0.37	171	171
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.12	0.22	0.31	1	-0.42	146	147
STAT1/PIAS1	-0.11	0.22	0.32	1	-0.43	127	128
GRB2/SOS1/GAB family/SHP2/PI3K	0.031	0.067	-10000	0	-0.38	4	4
STAT3 (dimer)	-0.15	0.37	-10000	0	-0.77	97	97
PRKCD	-0.1	0.27	-10000	0	-0.57	90	90
IL6R	0.002	0.085	-10000	0	-0.38	23	23
SOCS3	-0.1	0.23	-10000	0	-0.69	40	40
gp130 (dimer)/JAK1/JAK1/LMO4	-0.097	0.19	-10000	0	-0.35	171	171
Rac1/GTP	-0.11	0.24	-10000	0	-0.46	116	116
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	-0.17	0.38	-10000	0	-0.84	100	100
IRF1	-0.13	0.34	-10000	0	-0.76	79	79
mol:GDP	-0.12	0.23	0.29	1	-0.43	139	140
SOS1	0.018	0.024	-10000	0	-0.52	1	1
VAV1	-0.12	0.23	0.29	1	-0.44	139	140
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.12	0.22	-10000	0	-0.48	90	90
PTPN11	0.004	0.058	-10000	0	-1.2	1	1
IL6/IL6RA	-0.057	0.14	-10000	0	-0.36	76	76
gp130 (dimer)/TYK2/TYK2/LMO4	-0.096	0.18	-10000	0	-0.34	170	170
gp130 (dimer)/JAK2/JAK2/LMO4	-0.1	0.18	-10000	0	-0.35	175	175
IL6	-0.085	0.18	-10000	0	-0.36	146	146
PIAS3	0.018	0	-10000	0	-10000	0	0
PTPRE	0	0.082	-10000	0	-0.46	15	15
PIAS1	0.017	0.012	-10000	0	-0.26	1	1
RAC1	0.018	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.12	0.18	0.27	1	-0.34	167	168
LMO4	-0.074	0.18	-10000	0	-0.38	124	124
STAT3 (dimer)/PIAS3	-0.14	0.34	-10000	0	-0.72	98	98
MCL1	0.043	0.084	-10000	0	-1.2	1	1

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.017	0.16	0.34	14	-0.84	11	25
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	-0.76	118	118
SUMO2	0.014	0.022	-10000	0	-0.26	3	3
STAT1 (dimer)	-0.024	0.14	-10000	0	-0.35	67	67
FKBP4	0.012	0.055	-10000	0	-0.45	7	7
FKBP5	-0.045	0.16	-10000	0	-0.43	75	75
GR alpha/HSP90/FKBP51/HSP90	0.073	0.16	0.3	67	-0.31	28	95
PRL	-0.057	0.14	-10000	0	-0.87	3	3
cortisol/GR alpha (dimer)/TIF2	0.24	0.26	0.53	186	-0.4	2	188
RELA	-0.053	0.091	-10000	0	-0.26	22	22
FGG	0.2	0.22	0.49	135	-0.39	2	137
GR beta/TIF2	0.11	0.14	0.3	108	-0.31	14	122
IFNG	-0.41	0.43	-10000	0	-0.88	182	182
apoptosis	-0.005	0.18	0.49	7	-0.5	8	15
CREB1	0.007	0.057	-10000	0	-0.36	5	5
histone acetylation	-0.045	0.14	0.28	2	-0.36	51	53
BGLAP	-0.074	0.15	-10000	0	-0.6	8	8
GR/PKAc	0.093	0.14	0.3	58	-0.34	12	70
NF kappa B1 p50/RelA	-0.093	0.17	-10000	0	-0.38	78	78
SMARCD1	0.018	0	-10000	0	-10000	0	0
MDM2	0.099	0.1	0.24	121	-10000	0	121
GATA3	-0.093	0.23	-10000	0	-0.5	124	124
AKT1	0.007	0.06	0.21	4	-0.38	9	13
CSF2	-0.074	0.15	-10000	0	-0.66	13	13
GSK3B	0.016	0.008	-10000	0	-10000	0	0
NR1I3	0.008	0.18	0.48	6	-0.91	3	9
CSN2	0.17	0.18	0.41	125	-0.39	5	130
BRG1/BAF155/BAF170/BAF60A	0.041	0.034	-10000	0	-0.27	5	5
NFATC1	-0.004	0.12	-10000	0	-0.42	38	38
POU2F1	0.025	0.012	-10000	0	-0.22	1	1
CDKN1A	-0.033	0.27	-10000	0	-1.5	15	15
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	0.3	59	-0.32	29	88
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.086	0.33	0.46	6	-0.8	79	85
JUN	-0.22	0.24	-10000	0	-0.53	145	145
IL4	-0.1	0.2	-10000	0	-0.66	29	29
CDK5R1	0.013	0.032	-10000	0	-0.26	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	218	264
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.081	0.15	0.3	64	-0.3	23	87
cortisol/GR alpha (monomer)	0.28	0.32	0.63	190	-0.47	2	192
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	-0.45	171	171
AP-1/NFAT1-c-4	-0.44	0.39	-10000	0	-0.79	246	246
AFP	-0.16	0.2	-10000	0	-0.6	42	42
SUV420H1	0.014	0.037	-10000	0	-0.3	7	7
IRF1	0.11	0.25	0.43	63	-0.79	20	83
TP53	-0.014	0.17	-10000	0	-0.54	46	46
PPP5C	0.012	0.052	-10000	0	-0.39	8	8
KRT17	-0.54	0.58	-10000	0	-1.1	211	211
KRT14	-0.32	0.51	-10000	0	-1.3	100	100
TBP	0.028	0.011	-10000	0	-10000	0	0
CREBBP	0.061	0.1	0.26	65	-0.53	2	67
HDAC1	0.011	0.025	-10000	0	-0.53	1	1
HDAC2	0.008	0.054	-10000	0	-0.29	15	15
AP-1	-0.45	0.4	-10000	0	-0.8	248	248
MAPK14	0.015	0.014	-10000	0	-0.26	1	1
MAPK10	-0.027	0.13	-10000	0	-0.36	59	59
MAPK11	0.016	0.008	-10000	0	-10000	0	0
KRT5	-0.55	0.58	-10000	0	-1.1	238	238
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	-0.024	0.14	-10000	0	-0.35	67	67
CGA	-0.12	0.2	-10000	0	-0.53	59	59
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.12	0.17	0.37	111	-0.35	4	115
MAPK3	0.014	0.027	-10000	0	-0.39	2	2
MAPK1	0.014	0.034	-10000	0	-0.52	2	2
ICAM1	-0.23	0.34	-10000	0	-0.71	127	127
NFKB1	-0.054	0.093	-10000	0	-0.25	34	34
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	0.49	7	-0.53	8	15
BAX	0.002	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	160	-0.48	4	164
proteasomal ubiquitin-dependent protein catabolic process	0.071	0.081	0.22	67	-10000	0	67
SGK1	0.11	0.13	0.34	101	-0.26	4	105
IL13	-0.31	0.29	-10000	0	-0.7	138	138
IL6	-0.29	0.41	-10000	0	-0.93	117	117
PRKACG	0.016	0.033	-10000	0	-0.52	2	2
IL5	-0.27	0.24	-10000	0	-0.77	34	34
IL2	-0.32	0.33	-10000	0	-0.74	147	147
CDK5	0.015	0.027	-10000	0	-0.4	2	2
PRKACB	-0.035	0.14	-10000	0	-0.34	78	78
HSP90AA1	0.013	0.045	-10000	0	-0.39	6	6
IL8	-0.27	0.37	-10000	0	-0.78	139	139
CDK5R1/CDK5	0.02	0.03	-10000	0	-0.37	1	1
NF kappa B1 p50/RelA/PKAc	-0.064	0.15	-10000	0	-0.38	47	47
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.23	0.24	0.52	177	-10000	0	177
SMARCA4	0.015	0.031	-10000	0	-0.32	4	4
chromatin remodeling	0.16	0.16	0.36	147	-10000	0	147
NF kappa B1 p50/RelA/Cbp	-0.019	0.16	0.32	22	-0.39	25	47
JUN (dimer)	-0.22	0.24	-10000	0	-0.52	145	145
YWHAH	0.013	0.048	-10000	0	-0.47	5	5
VIPR1	-0.11	0.23	-10000	0	-0.61	70	70
NR3C1	0.16	0.21	0.42	141	-0.45	11	152
NR4A1	0.01	0.064	-10000	0	-0.44	4	4
TIF2/SUV420H1	0.017	0.056	-10000	0	-0.42	6	6
MAPKKK cascade	-0.005	0.18	0.49	7	-0.5	8	15
cortisol/GR alpha (dimer)/Src-1	0.24	0.26	0.54	184	-0.43	3	187
PBX1	0.004	0.1	-10000	0	-0.48	23	23
POU1F1	0.023	0.034	-10000	0	-0.3	5	5
SELE	-0.36	0.48	-10000	0	-1	157	157
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.16	0.16	0.36	147	-10000	0	147
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.23	0.24	0.52	177	-10000	0	177
mol:cortisol	0.16	0.19	0.37	191	-10000	0	191
MMP1	-0.44	0.52	-10000	0	-1.3	132	132

×

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	0.62	-10000	0	-1.3	117	117
STAT6 (cleaved dimer)	-0.43	0.56	-10000	0	-1.2	143	143
IGHG1	-0.081	0.25	-10000	0	-0.44	65	65
IGHG3	-0.33	0.59	-10000	0	-1.2	138	138
AKT1	-0.11	0.31	-10000	0	-0.71	42	42
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.063	0.24	-10000	0	-0.68	19	19
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.14	0.34	-10000	0	-0.76	59	59
THY1	-0.34	0.65	-10000	0	-1.3	123	123
MYB	-0.098	0.22	-10000	0	-0.49	121	121
HMGA1	0.014	0.039	-10000	0	-0.36	5	5
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.14	0.35	-10000	0	-0.65	93	93
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.12	0.31	-10000	0	-0.78	30	30
SP1	0.021	0.03	-10000	0	-0.53	1	1
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.015	0.055	-10000	0	-0.4	7	7
STAT6 (dimer)/ETS1	-0.33	0.63	-10000	0	-1.2	135	135
SOCS1	-0.18	0.4	-10000	0	-0.78	101	101
SOCS3	-0.11	0.33	-10000	0	-0.92	26	26
FCER2	-0.22	0.46	-10000	0	-0.91	101	101
PARP14	0.006	0.078	-10000	0	-0.43	15	15
CCL17	-0.41	0.71	-10000	0	-1.4	154	154
GRB2	0.016	0.024	-10000	0	-0.26	4	4
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.081	0.26	-10000	0	-0.67	22	22
T cell proliferation	-0.35	0.65	-10000	0	-1.3	126	126
IL4R/JAK1	-0.34	0.64	-10000	0	-1.3	123	123
EGR2	-0.38	0.69	-10000	0	-1.4	137	137
JAK2	0.001	0.072	-10000	0	-0.35	12	12
JAK3	0.021	0.008	-10000	0	-10000	0	0
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
JAK1	0.012	0.061	-10000	0	-0.52	6	6
COL1A2	-0.22	0.54	-10000	0	-1.5	70	70
CCL26	-0.33	0.63	-10000	0	-1.3	121	121
IL4R	-0.37	0.7	-10000	0	-1.4	120	120
PTPN6	0.02	0.038	-10000	0	-0.42	3	3
IL13RA2	-0.38	0.67	-10000	0	-1.3	142	142
IL13RA1	-0.002	0.089	-10000	0	-0.49	12	12
IRF4	-0.037	0.2	-10000	0	-0.88	8	8
ARG1	-0.063	0.27	-10000	0	-0.98	22	22
CBL	-0.13	0.32	-10000	0	-0.61	90	90
GTF3A	0.02	0.032	-10000	0	-0.38	2	2
PIK3CA	0.016	0.029	-10000	0	-0.35	3	3
IL13RA1/JAK2	0.004	0.099	-10000	0	-0.36	18	18
IRF4/BCL6	-0.043	0.19	-10000	0	-0.86	7	7
CD40LG	0.012	0.072	-10000	0	-0.32	21	21
MAPK14	-0.13	0.33	-10000	0	-0.65	75	75
mitosis	-0.1	0.3	-10000	0	-0.66	42	42
STAT6	-0.43	0.85	-10000	0	-1.6	138	138
SPI1	0.011	0.074	-10000	0	-0.44	12	12
RPS6KB1	-0.097	0.29	-10000	0	-0.66	35	35
STAT6 (dimer)	-0.43	0.86	-10000	0	-1.6	138	138
STAT6 (dimer)/PARP14	-0.38	0.7	-10000	0	-1.4	139	139
mast cell activation	0.003	0.019	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.11	0.3	-10000	0	-0.69	45	45
FRAP1	-0.11	0.31	-10000	0	-0.7	42	42
LTA	-0.33	0.62	-10000	0	-1.3	115	115
FES	0.011	0.054	-10000	0	-0.38	9	9
T-helper 1 cell differentiation	0.39	0.75	1.4	138	-10000	0	138
CCL11	-0.38	0.65	-10000	0	-1.3	141	141
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.099	0.3	-10000	0	-0.7	30	30
IL2RG	0.001	0.081	-10000	0	-0.29	35	35
IL10	-0.33	0.63	-10000	0	-1.3	117	117
IRS1	-0.048	0.17	-10000	0	-0.49	68	68
IRS2	-0.026	0.13	-10000	0	-0.39	57	57
IL4	-0.038	0.22	-10000	0	-1.4	6	6
IL5	-0.33	0.63	-10000	0	-1.4	99	99
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.24	0.5	-10000	0	-0.95	126	126
COL1A1	-0.22	0.56	-10000	0	-1.5	71	71
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.36	0.67	-10000	0	-1.5	103	103
IL2R gamma/JAK3	0.017	0.059	-10000	0	-0.33	5	5
TFF3	-0.51	0.77	-10000	0	-1.4	190	190
ALOX15	-0.34	0.64	-10000	0	-1.3	119	119
MYBL1	-0.067	0.17	-10000	0	-0.37	116	116
T-helper 2 cell differentiation	-0.25	0.49	-10000	0	-0.96	124	124
SHC1	0.017	0.023	-10000	0	-0.52	1	1
CEBPB	0.008	0.075	-10000	0	-0.33	21	21
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.12	0.32	-10000	0	-0.75	40	40
mol:PI-3-4-5-P3	-0.11	0.31	-10000	0	-0.7	42	42
PI3K	-0.12	0.33	-10000	0	-0.76	42	42
DOK2	-0.021	0.13	-10000	0	-0.41	48	48
ETS1	0.007	0.067	-10000	0	-0.35	9	9
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.071	0.25	-10000	0	-0.62	23	23
ITGB3	-0.34	0.63	-10000	0	-1.3	122	122
PIGR	-0.49	0.76	-10000	0	-1.4	181	181
IGHE	0.022	0.086	0.21	44	-0.25	4	48
MAPKKK cascade	-0.069	0.24	-10000	0	-0.61	23	23
BCL6	-0.005	0.1	-10000	0	-0.46	24	24
OPRM1	-0.33	0.63	-10000	0	-1.3	116	116
RETNLB	-0.33	0.63	-10000	0	-1.3	115	115
SELP	-0.46	0.75	-10000	0	-1.5	158	158
AICDA	-0.34	0.61	-10000	0	-1.3	126	126

×

TCR signaling in naïve CD8+ T 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	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	94	94
FYN	-0.085	0.26	-10000	0	-0.55	106	106
LAT/GRAP2/SLP76	-0.099	0.21	-10000	0	-0.48	109	109
IKBKB	0.011	0.047	-10000	0	-0.31	10	10
AKT1	-0.048	0.19	-10000	0	-0.38	109	109
B2M	-0.006	0.11	-10000	0	-0.46	26	26
IKBKG	0.002	0.062	-10000	0	-0.13	54	54
MAP3K8	-0.036	0.15	-10000	0	-0.39	69	69
mol:Ca2+	-0.022	0.031	-10000	0	-0.072	106	106
integrin-mediated signaling pathway	0.007	0.067	-10000	0	-0.31	19	19
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.084	0.26	-10000	0	-0.54	112	112
TRPV6	-0.11	0.19	-10000	0	-0.38	160	160
CD28	-0.044	0.16	-10000	0	-0.4	78	78
SHC1	-0.09	0.26	-10000	0	-0.56	103	103
receptor internalization	-0.12	0.3	-10000	0	-0.6	121	121
PRF1	-0.081	0.25	-10000	0	-0.72	45	45
KRAS	0.008	0.069	-10000	0	-0.45	11	11
GRB2	0.016	0.024	-10000	0	-0.26	4	4
COT/AKT1	-0.047	0.16	-10000	0	-0.32	103	103
LAT	-0.096	0.27	-10000	0	-0.56	112	112
EntrezGene:6955	0	0.004	-10000	0	-10000	0	0
CD3D	-0.028	0.13	-10000	0	-0.35	66	66
CD3E	0.016	0.018	-10000	0	-0.27	2	2
CD3G	-0.092	0.2	-10000	0	-0.42	135	135
RASGRP2	-0.002	0.036	-10000	0	-0.14	17	17
RASGRP1	-0.061	0.2	-10000	0	-0.38	121	121
HLA-A	-0.013	0.12	-10000	0	-0.44	35	35
RASSF5	-0.002	0.091	-10000	0	-0.38	27	27
RAP1A/GTP/RAPL	0.008	0.067	-10000	0	-0.31	19	19
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	-0.2	88	88
PRKCA	-0.044	0.11	-10000	0	-0.24	96	96
GRAP2	0.011	0.044	-10000	0	-0.28	11	11
mol:IP3	-0.052	0.19	0.19	83	-0.37	105	188
EntrezGene:6957	-0.001	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.081	0.22	-10000	0	-0.46	99	99
ORAI1	0.071	0.11	0.3	68	-0.38	1	69
CSK	-0.089	0.26	-10000	0	-0.56	103	103
B7 family/CD28	-0.11	0.3	-10000	0	-0.6	118	118
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	-0.64	106	106
PTPN6	-0.094	0.26	-10000	0	-0.57	103	103
VAV1	-0.1	0.28	-10000	0	-0.59	107	107
Monovalent TCR/CD3	-0.095	0.22	-10000	0	-0.4	145	145
CBL	0.017	0.012	-10000	0	-0.26	1	1
LCK	-0.098	0.28	-10000	0	-0.59	107	107
PAG1	-0.093	0.26	-10000	0	-0.57	104	104
RAP1A	0.011	0.062	-10000	0	-0.52	7	7
TCR/CD3/MHC I/CD8/LCK	-0.12	0.3	-10000	0	-0.61	117	117
CD80	0.009	0.049	-10000	0	-0.28	14	14
CD86	-0.009	0.12	-10000	0	-0.5	27	27
PDK1/CARD11/BCL10/MALT1	-0.055	0.095	-10000	0	-0.24	92	92
HRAS	0.012	0.051	-10000	0	-0.41	7	7
GO:0035030	-0.091	0.24	-10000	0	-0.5	118	118
CD8A	0	0.005	-10000	0	-10000	0	0
CD8B	0.001	0.07	-10000	0	-0.28	29	29
PTPRC	-0.041	0.16	-10000	0	-0.42	71	71
PDK1/PKC theta	-0.061	0.23	-10000	0	-0.47	109	109
CSK/PAG1	-0.08	0.25	-10000	0	-0.54	98	98
SOS1	0.017	0.023	-10000	0	-0.52	1	1
peptide-MHC class I	-0.012	0.13	-10000	0	-0.47	33	33
GRAP2/SLP76	-0.086	0.26	-10000	0	-0.55	107	107
STIM1	0.035	0.059	-10000	0	-0.36	2	2
RAS family/GTP	-0.002	0.088	-10000	0	-0.17	68	68
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.13	0.33	-10000	0	-0.64	121	121
mol:DAG	-0.072	0.15	-10000	0	-0.33	108	108
RAP1A/GDP	0.002	0.032	-10000	0	-0.08	20	20
PLCG1	0.016	0.026	-10000	0	-0.39	2	2
CD247	-0.1	0.21	-10000	0	-0.42	151	151
cytotoxic T cell degranulation	-0.077	0.24	-10000	0	-0.69	45	45
RAP1A/GTP	-0.005	0.015	-10000	0	-0.076	18	18
mol:PI-3-4-5-P3	-0.064	0.22	-10000	0	-0.45	112	112
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.076	0.23	0.21	78	-0.48	107	185
NRAS	0.006	0.072	-10000	0	-0.4	15	15
ZAP70	0.005	0.061	-10000	0	-0.27	24	24
GRB2/SOS1	0.024	0.024	-10000	0	-0.37	1	1
LAT/GRAP2/SLP76/VAV1	-0.1	0.21	0.16	1	-0.48	110	111
MALT1	0.011	0.054	-10000	0	-0.38	9	9
TRAF6	0.017	0.023	-10000	0	-0.52	1	1
CD8 heterodimer	0.002	0.049	-10000	0	-0.2	29	29
CARD11	0.002	0.078	-10000	0	-0.34	24	24
PRKCB	-0.048	0.1	-10000	0	-0.23	110	110
PRKCE	-0.045	0.11	-10000	0	-0.24	98	98
PRKCQ	-0.079	0.26	-10000	0	-0.52	113	113
LCP2	-0.005	0.1	-10000	0	-0.41	28	28
BCL10	0.017	0.012	-10000	0	-0.26	1	1
regulation of survival gene product expression	-0.037	0.16	-10000	0	-0.32	108	108
IKK complex	0.012	0.059	-10000	0	-0.1	52	52
RAS family/GDP	-0.008	0.015	-10000	0	-0.064	20	20
MAP3K14	-0.029	0.13	-10000	0	-0.25	91	91
PDPK1	-0.042	0.18	-10000	0	-0.36	105	105
TCR/CD3/MHC I/CD8/Fyn	-0.092	0.26	-10000	0	-0.59	92	92

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.03	0.12	-10000	0	-0.32	38	38
TBX21	-0.3	0.59	-10000	0	-1.3	119	119
B2M	-0.006	0.1	-10000	0	-0.45	26	26
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	89	89
IL12RB2	-0.076	0.16	-10000	0	-0.32	141	141
GADD45G	-0.18	0.43	-10000	0	-0.98	97	97
natural killer cell activation	-0.005	0.024	-10000	0	-10000	0	0
RELB	0.003	0.079	-10000	0	-0.38	19	19
RELA	0.018	0	-10000	0	-10000	0	0
IL18	-0.048	0.17	-10000	0	-0.44	78	78
IL2RA	-0.031	0.14	-10000	0	-0.41	61	61
IFNG	-0.089	0.17	-10000	0	-0.33	161	161
STAT3 (dimer)	-0.14	0.37	-10000	0	-0.76	112	112
HLA-DRB5	-0.004	0.098	-10000	0	-0.51	19	19
FASLG	-0.24	0.52	-10000	0	-1.1	110	110
NF kappa B2 p52/RelB	-0.24	0.41	-10000	0	-0.87	129	129
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	-0.032	0.13	-10000	0	-0.35	66	66
CD3E	0.013	0.021	-10000	0	-0.28	2	2
CD3G	-0.097	0.2	-10000	0	-0.42	135	135
IL12Rbeta2/JAK2	-0.048	0.13	-10000	0	-0.27	102	102
CCL3	-0.2	0.44	-10000	0	-0.97	102	102
CCL4	-0.2	0.46	-10000	0	-1	103	103
HLA-A	-0.013	0.12	-10000	0	-0.43	35	35
IL18/IL18R	-0.059	0.22	-10000	0	-0.41	117	117
NOS2	-0.19	0.43	-10000	0	-0.86	124	124
IL12/IL12R/TYK2/JAK2/SPHK2	-0.03	0.12	-10000	0	-0.33	37	37
IL1R1	-0.25	0.51	-10000	0	-1.1	118	118
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	-0.65	105	105
RAB7A	-0.12	0.34	-10000	0	-0.8	81	81
lysosomal transport	-0.12	0.33	-10000	0	-0.75	82	82
FOS	-0.29	0.49	-10000	0	-1.1	132	132
STAT4 (dimer)	-0.18	0.43	-10000	0	-0.88	119	119
STAT5A (dimer)	-0.27	0.42	-10000	0	-0.89	136	136
GZMA	-0.2	0.43	-10000	0	-0.87	126	126
GZMB	-0.28	0.57	-10000	0	-1.2	119	119
HLX	0.005	0.079	-10000	0	-0.48	13	13
LCK	-0.25	0.52	-10000	0	-1	137	137
TCR/CD3/MHC II/CD4	-0.11	0.23	-10000	0	-0.46	122	122
IL2/IL2R	-0.015	0.14	-10000	0	-0.34	71	71
MAPK14	-0.18	0.44	-10000	0	-0.94	104	104
CCR5	-0.19	0.46	-10000	0	-1	94	94
IL1B	-0.053	0.17	-10000	0	-0.42	81	81
STAT6	-0.067	0.18	-10000	0	-0.38	76	76
STAT4	-0.023	0.13	-10000	0	-0.42	49	49
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	0.078	-10000	0	-0.35	21	21
CD8A	-0.001	0.008	-10000	0	-10000	0	0
CD8B	0.001	0.071	-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	0.32	38	-10000	0	38
IL2RB	-0.017	0.12	-10000	0	-0.44	40	40
proteasomal ubiquitin-dependent protein catabolic process	-0.16	0.38	-10000	0	-0.78	119	119
IL2RG	-0.003	0.079	-10000	0	-0.29	35	35
IL12	-0.012	0.09	-10000	0	-0.26	35	35
STAT5A	0.011	0.056	-10000	0	-0.42	8	8
CD247	-0.11	0.21	-10000	0	-0.42	151	151
IL2	0.011	0.051	-10000	0	-0.34	10	10
SPHK2	0.016	0.033	-10000	0	-0.52	2	2
FRAP1	0.018	0	-10000	0	-10000	0	0
IL12A	-0.02	0.097	-10000	0	-0.28	56	56
IL12/IL12R/TYK2/JAK2	-0.25	0.54	-10000	0	-1.1	126	126
MAP2K3	-0.18	0.44	-10000	0	-0.94	107	107
RIPK2	0.013	0.041	-10000	0	-0.29	9	9
MAP2K6	-0.19	0.45	-10000	0	-0.95	109	109
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	-0.074	0.19	-10000	0	-0.41	117	117
IL12Rbeta1/TYK2	0.018	0.032	-10000	0	-10000	0	0
EOMES	-0.057	0.26	-10000	0	-1.3	20	20
STAT1 (dimer)	-0.2	0.39	-10000	0	-0.79	126	126
T cell proliferation	-0.12	0.31	-10000	0	-0.64	115	115
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	-0.68	122	122
ATF2	-0.15	0.4	-10000	0	-0.85	102	102

×

IL27-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
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	0.64	93	-10000	0	93
IL27/IL27R/JAK1	-0.2	0.35	-10000	0	-0.94	69	69
TBX21	-0.22	0.3	-10000	0	-0.62	146	146
IL12B	0.001	0.075	-10000	0	-0.35	21	21
IL12A	-0.01	0.066	-10000	0	-0.19	56	56
IL6ST	-0.12	0.22	-10000	0	-0.47	143	143
IL27RA/JAK1	-0.11	0.32	-10000	0	-1.2	38	38
IL27	-0.083	0.2	-10000	0	-0.5	99	99
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	0.64	93	-10000	0	93
T cell proliferation during immune response	0.17	0.26	0.64	93	-10000	0	93
MAPKKK cascade	-0.17	0.26	-10000	0	-0.64	93	93
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	-0.61	134	134
IL27/IL27R/JAK2/TYK2	-0.17	0.26	-10000	0	-0.65	93	93
positive regulation of T cell mediated cytotoxicity	-0.17	0.26	-10000	0	-0.64	93	93
STAT1 (dimer)	-0.27	0.39	0.48	7	-0.98	86	93
JAK2	0.004	0.055	-10000	0	-0.34	12	12
JAK1	0.011	0.057	-10000	0	-0.52	6	6
STAT2 (dimer)	-0.16	0.25	-10000	0	-0.61	92	92
T cell proliferation	-0.2	0.27	-10000	0	-0.62	114	114
IL12/IL12R/TYK2/JAK2	-0.034	0.15	-10000	0	-0.85	9	9
IL17A	-0.006	0.11	-10000	0	-1.4	1	1
mast cell activation	0.17	0.26	0.64	93	-10000	0	93
IFNG	-0.032	0.047	-10000	0	-0.11	96	96
T cell differentiation	-0.01	0.009	0.024	1	-0.022	151	152
STAT3 (dimer)	-0.16	0.25	-10000	0	-0.61	93	93
STAT5A (dimer)	-0.16	0.26	-10000	0	-0.62	94	94
STAT4 (dimer)	-0.17	0.27	-10000	0	-0.61	110	110
STAT4	-0.023	0.13	-10000	0	-0.42	49	49
T cell activation	0.002	0.038	0.11	45	-10000	0	45
IL27R/JAK2/TYK2	-0.16	0.33	-10000	0	-0.98	56	56
GATA3	-0.25	0.55	-10000	0	-1.3	119	119
IL18	-0.036	0.12	-10000	0	-0.31	78	78
positive regulation of mast cell cytokine production	-0.15	0.25	-10000	0	-0.6	93	93
IL27/EBI3	-0.061	0.16	-10000	0	-0.39	92	92
IL27RA	-0.12	0.34	-10000	0	-1.3	37	37
IL6	-0.079	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	37	-1.2	3	40
IL1B	-0.034	0.12	-10000	0	-0.29	81	81
EBI3	0.001	0.071	-10000	0	-0.44	12	12
TNF	-0.003	0.067	-10000	0	-0.25	31	31

×

Fc-epsilon receptor I signaling in mast 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.007	0.074	-9999	-0.5	11	11
LAT2	-0.088	0.18	-9999	-0.42	86	86
AP1	-0.14	0.22	-9999	-0.5	116	116
mol:PIP3	-0.1	0.22	-9999	-0.48	95	95
IKBKB	-0.044	0.12	-9999	-0.26	87	87
AKT1	-0.067	0.16	-9999	-0.4	74	74
IKBKG	-0.042	0.12	-9999	-0.25	90	90
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	-0.35	3	3
MAP3K1	-0.086	0.2	-9999	-0.43	99	99
mol:Ca2+	-0.071	0.16	-9999	-0.36	95	95
LYN	0.012	0.033	-9999	-0.27	7	7
CBLB	-0.086	0.18	-9999	-0.42	81	81
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	-0.015	0.092	-9999	-0.29	48	48
INPP5D	0	0	-9999	-10000	0	0
PLD2	-0.088	0.18	-9999	-0.38	106	106
PTPN13	-0.12	0.21	-9999	-0.55	77	77
PTPN11	0.013	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	75	75
SYK	-0.024	0.14	-9999	-0.49	42	42
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	-0.43	84	84
PAK2	-0.081	0.2	-9999	-0.45	88	88
NFATC2	-0.042	0.082	-9999	-0.62	5	5
HRAS	-0.096	0.21	-9999	-0.48	93	93
GAB2	0.009	0.047	-9999	-0.26	16	16
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	94	94
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	32	32
FOS	-0.11	0.2	-9999	-0.37	171	171
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.097	0.18	-9999	-0.36	138	138
CHUK	-0.046	0.12	-9999	-0.26	93	93
KLRG1	-0.083	0.17	-9999	-0.41	75	75
VAV1	-0.1	0.2	-9999	-0.45	91	91
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.085	0.18	-9999	-0.43	76	76
negative regulation of mast cell degranulation	-0.078	0.16	-9999	-0.39	75	75
BTK	-0.11	0.23	-9999	-0.53	89	89
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.13	0.25	-9999	-0.5	123	123
GAB2/PI3K/SHP2	-0.1	0.15	-9999	-0.43	76	76
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.096	0.2	-9999	-0.5	78	78
RAF1	0.029	0.026	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.12	0.21	-9999	-0.36	185	185
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	169	169
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	-0.2	17	17
actin cytoskeleton reorganization	-0.087	0.18	-9999	-0.47	68	68
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	-0.41	83	83
RELA	0.018	0	-9999	-10000	0	0
ITK	-0.052	0.13	-9999	-0.42	47	47
SOS1	0.017	0.023	-9999	-0.52	1	1
PLCG1	-0.1	0.22	-9999	-0.51	92	92
cytokine secretion	-0.029	0.044	-9999	-0.19	1	1
SPHK1	-0.11	0.2	-9999	-0.43	104	104
PTK2	-0.091	0.19	-9999	-0.5	66	66
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.21	-9999	-0.51	98	98
EDG1	-0.015	0.092	-9999	-0.29	48	48
mol:DAG	-0.095	0.22	-9999	-0.47	99	99
MAP2K2	0.032	0.031	-9999	-10000	0	0
MAP2K1	0.033	0.024	-9999	-10000	0	0
MAP2K7	0.017	0.023	-9999	-0.52	1	1
KLRG1/SHP2	-0.072	0.15	-9999	-0.39	70	70
MAP2K4	-0.011	0.16	-9999	-0.91	16	16
Fc epsilon R1/FcgammaRIIB	-0.12	0.22	-9999	-0.38	185	185
mol:Choline	-0.086	0.17	-9999	-0.37	106	106
SHC/Grb2/SOS1	-0.066	0.17	-9999	-0.42	68	68
FYN	0.009	0.063	-9999	-0.4	11	11
DOK1	0.002	0.083	-9999	-0.41	19	19
PXN	-0.078	0.18	-9999	-0.46	65	65
HCLS1	-0.095	0.19	-9999	-0.44	90	90
PRKCB	-0.069	0.16	-9999	-0.35	99	99
FCGR2B	-0.032	0.15	-9999	-0.5	51	51
IGHE	-0.003	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.08	0.16	-9999	-0.4	75	75
LCP2	-0.005	0.1	-9999	-0.41	28	28
PLA2G4A	-0.11	0.21	-9999	-0.46	106	106
RASA1	0.004	0.079	-9999	-0.42	16	16
mol:Phosphatidic acid	-0.086	0.17	-9999	-0.37	106	106
IKK complex	-0.023	0.098	-9999	-0.2	76	76
WIPF1	0.005	0.076	-9999	-0.41	16	16

×

Arf6 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
CENTA1/KIF3B	0	0.058	-10000	0	-0.26	23	23
ARNO/beta Arrestin1-2	-0.013	0.09	-10000	0	-0.24	59	59
EGFR	-0.077	0.17	-10000	0	-0.35	136	136
EPHA2	0.008	0.06	-10000	0	-0.33	14	14
USP6	0.011	0.041	-10000	0	-0.26	12	12
IQSEC1	0.016	0.026	-10000	0	-0.39	2	2
EGFR/EGFR/EGF/EGF	-0.15	0.2	-10000	0	-0.42	172	172
ARRB2	0.011	0.052	-10000	0	-0.32	12	12
mol:GTP	0.006	0.015	0.066	1	-0.13	2	3
ARRB1	0.004	0.075	-10000	0	-0.38	18	18
FBXO8	0.015	0.04	-10000	0	-0.52	3	3
TSHR	0.008	0.071	-10000	0	-0.5	10	10
EGF	-0.14	0.23	-10000	0	-0.42	193	193
somatostatin receptor activity	0	0	-10000	0	-0.001	102	102
ARAP2	0	0	-10000	0	0	117	117
mol:GDP	-0.054	0.11	-10000	0	-0.25	91	91
mol:PI-3-4-5-P3	0	0	-10000	0	-0.001	103	103
ITGA2B	0.016	0.021	-10000	0	-0.26	3	3
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
ADAP1	0	0	-10000	0	0	90	90
KIF13B	-0.002	0.095	-10000	0	-0.43	23	23
HGF/MET	0.006	0.075	-10000	0	-0.38	14	14
PXN	0.018	0	-10000	0	-10000	0	0
ARF6/GTP	-0.067	0.11	-10000	0	-0.26	99	99
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.12	0.18	-10000	0	-0.35	172	172
ADRB2	-0.045	0.16	-10000	0	-0.4	80	80
receptor agonist activity	0	0	-10000	0	0	101	101
actin filament binding	0	0	-10000	0	0	101	101
SRC	0.015	0.035	-10000	0	-0.43	3	3
ITGB3	0.002	0.076	-10000	0	-0.32	25	25
GNAQ	0	0	-10000	0	-0.001	96	96
EFA6/PI-4-5-P2	0	0	-10000	0	-0.001	96	96
ARF6/GDP	-0.003	0.059	-10000	0	-0.3	5	5
ARF6/GDP/GULP/ACAP1	-0.057	0.13	-10000	0	-0.3	92	92
alphaIIb/beta3 Integrin/paxillin/GIT1	0.034	0.048	-10000	0	-0.26	8	8
ACAP1	0	0	-10000	0	0	30	30
ACAP2	0	0	-10000	0	0	115	115
LHCGR/beta Arrestin2	0.009	0.07	-10000	0	-0.44	12	12
EFNA1	0	0.094	-10000	0	-0.49	18	18
HGF	0.008	0.069	-10000	0	-0.45	11	11
CYTH3	0	0	-10000	0	-0.001	102	102
CYTH2	-0.001	0.002	-10000	0	-0.004	107	107
NCK1	0.011	0.046	-10000	0	-0.28	12	12
fibronectin binding	0	0	-10000	0	0	85	85
endosomal lumen acidification	0	0	-10000	0	0	95	95
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	-0.033	0.15	-10000	0	-0.44	59	59
GNAQ/ARNO	-0.001	0.003	-10000	0	-0.006	94	94
mol:Phosphatidic acid	0	0	-10000	0	0	115	115
PIP3-E	0.004	0.069	-10000	0	-0.3	23	23
MET	-0.001	0.078	-10000	0	-0.3	31	31
GNA14	-0.081	0.18	-10000	0	-0.35	141	141
GNA15	0.001	0.078	-10000	0	-0.33	25	25
GIT1	0.014	0.035	-10000	0	-0.3	6	6
mol:PI-4-5-P2	0	0	-10000	0	-0.001	97	97
GNA11	0.013	0.047	-10000	0	-0.52	4	4
LHCGR	0.003	0.083	-10000	0	-0.46	16	16
AGTR1	-0.15	0.21	-10000	0	-0.36	229	229
desensitization of G-protein coupled receptor protein signaling pathway	0.009	0.07	-10000	0	-0.44	12	12
IPCEF1/ARNO	-0.095	0.14	-10000	0	-0.28	178	178
alphaIIb/beta3 Integrin	0.014	0.056	-10000	0	-0.36	7	7

×

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	-0.063	0.17	-9999	-0.43	52	52
NF kappa B1 p50/RelA/I kappa B alpha	-0.044	0.18	-9999	-0.47	47	47
alphaV/beta3 Integrin/Osteopontin/Src	-0.099	0.19	-9999	-0.39	134	134
AP1	-0.15	0.26	-9999	-0.6	93	93
ILK	-0.065	0.16	-9999	-0.42	43	43
bone resorption	-0.056	0.17	-9999	-0.42	50	50
PTK2B	0.017	0.017	-9999	-0.26	2	2
PYK2/p130Cas	-0.059	0.17	-9999	-0.4	54	54
ITGAV	-0.002	0.1	-9999	-0.49	22	22
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.006	0.082	-9999	-0.37	22	22
alphaV/beta3 Integrin/Osteopontin	-0.078	0.18	-9999	-0.33	145	145
MAP3K1	-0.091	0.18	-9999	-0.32	169	169
JUN	-0.034	0.15	-9999	-0.46	57	57
MAPK3	-0.064	0.17	-9999	-0.46	48	48
MAPK1	-0.064	0.17	-9999	-0.46	49	49
Rac1/GDP	0.013	0	-9999	-10000	0	0
NFKB1	0.017	0.023	-9999	-0.52	1	1
MAPK8	-0.081	0.17	-9999	-0.41	67	67
ITGB3	0.003	0.078	-9999	-0.32	25	25
NFKBIA	-0.064	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	0.37	-9999	-1.2	53	53
NF kappa B1 p50/RelA	-0.047	0.19	-9999	-0.52	46	46
BCAR1	0.017	0.012	-9999	-0.26	1	1
RELA	0.018	0	-9999	-10000	0	0
alphaV beta3 Integrin	0.003	0.1	-9999	-0.42	23	23
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.086	0.18	-9999	-0.32	164	164
VAV3	-0.12	0.2	-9999	-0.44	97	97
MAP3K14	-0.07	0.17	-9999	-0.31	140	140
ROCK2	0.012	0.053	-9999	-0.48	6	6
SPP1	-0.14	0.23	-9999	-0.43	188	188
RAC1	0.018	0	-9999	-10000	0	0
Rac1/GTP	-0.11	0.18	-9999	-0.41	89	89
MMP2	-0.13	0.24	-9999	-0.55	96	96

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.2	-9999	-0.42	104	104
mol:DAG	-0.094	0.18	-9999	-0.47	63	63
PLCG1	-0.097	0.18	-9999	-0.49	62	62
YES1	-0.12	0.2	-9999	-0.45	105	105
FZD3	-0.031	0.15	-9999	-0.48	52	52
FZD6	-0.077	0.2	-9999	-0.45	108	108
G protein	-0.1	0.19	-9999	-0.49	65	65
MAP3K7	-0.069	0.15	-9999	-0.39	59	59
mol:Ca2+	-0.091	0.17	-9999	-0.45	63	63
mol:IP3	-0.094	0.18	-9999	-0.47	63	63
NLK	0.016	0.044	-9999	-0.9	1	1
GNB1	0.013	0.052	-9999	-0.52	5	5
CAMK2A	-0.08	0.16	-9999	-0.42	62	62
MAP3K7IP1	0.018	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.13	0.21	-9999	-0.47	103	103
CSNK1A1	0.017	0.023	-9999	-0.52	1	1
GNAS	-0.12	0.2	-9999	-0.44	105	105
GO:0007205	-0.093	0.18	-9999	-0.46	63	63
WNT6	-0.011	0.088	-9999	-0.27	54	54
WNT4	-0.063	0.18	-9999	-0.45	90	90
NFAT1/CK1 alpha	-0.092	0.19	-9999	-0.48	66	66
GNG2	0.016	0.029	-9999	-0.35	3	3
WNT5A	-0.084	0.2	-9999	-0.43	120	120
WNT11	-0.013	0.09	-9999	-0.27	57	57
CDC42	-0.11	0.2	-9999	-0.49	73	73

×

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	-0.24	0.54	-10000	0	-1.3	83	83
IL23A	-0.21	0.49	-10000	0	-1.2	71	71
NF kappa B1 p50/RelA/I kappa B alpha	-0.22	0.42	-10000	0	-1	90	90
positive regulation of T cell mediated cytotoxicity	-0.21	0.51	-10000	0	-1.1	92	92
ITGA3	-0.2	0.48	-10000	0	-1.1	82	82
IL17F	-0.1	0.32	-10000	0	-0.68	77	77
IL12B	0.003	0.084	-10000	0	-0.36	21	21
STAT1 (dimer)	-0.22	0.49	-10000	0	-1.1	93	93
CD4	-0.18	0.44	-10000	0	-1	74	74
IL23	-0.21	0.47	-10000	0	-1.2	71	71
IL23R	-0.013	0.18	-10000	0	-1.4	7	7
IL1B	-0.24	0.53	-10000	0	-1.3	83	83
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.18	0.44	-10000	0	-1.1	61	61
TYK2	0.013	0.024	-10000	0	-10000	0	0
STAT4	-0.023	0.13	-10000	0	-0.42	49	49
STAT3	0.015	0.041	-10000	0	-0.52	3	3
IL18RAP	-0.078	0.19	-10000	0	-0.41	117	117
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	0.03	-10000	0	-10000	0	0
IL23R/JAK2	-0.014	0.19	-10000	0	-1.3	7	7
positive regulation of chronic inflammatory response	-0.21	0.51	-10000	0	-1.1	92	92
natural killer cell activation	0.002	0.012	0.073	8	-10000	0	8
JAK2	0.01	0.065	-10000	0	-0.34	12	12
PIK3R1	-0.008	0.11	-10000	0	-0.42	32	32
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	-0.2	0.45	-10000	0	-1.1	71	71
ALOX12B	-0.18	0.44	-10000	0	-1.1	67	67
CXCL1	-0.27	0.54	-10000	0	-1.1	118	118
T cell proliferation	-0.21	0.51	-10000	0	-1.1	92	92
NFKBIA	0.014	0.043	-10000	0	-0.46	4	4
IL17A	-0.055	0.26	-10000	0	-0.55	56	56
PI3K	-0.19	0.47	-10000	0	-1.1	89	89
IFNG	-0.028	0.05	0.12	2	-0.12	63	65
STAT3 (dimer)	-0.21	0.42	-10000	0	-0.99	90	90
IL18R1	-0.014	0.11	-10000	0	-0.41	37	37
IL23/IL23R/JAK2/TYK2/SOCS3	-0.083	0.28	-10000	0	-0.63	48	48
IL18/IL18R	-0.085	0.2	-10000	0	-0.41	117	117
macrophage activation	-0.015	0.017	-10000	0	-0.044	69	69
TNF	-0.21	0.49	-10000	0	-1.2	75	75
STAT3/STAT4	-0.24	0.45	-10000	0	-1	97	97
STAT4 (dimer)	-0.22	0.5	-10000	0	-1.1	96	96
IL18	-0.052	0.17	-10000	0	-0.44	78	78
IL19	-0.19	0.44	-10000	0	-1.1	75	75
STAT5A (dimer)	-0.21	0.49	-10000	0	-1.1	92	92
STAT1	-0.02	0.12	-10000	0	-0.33	58	58
SOCS3	0.005	0.074	-10000	0	-0.38	17	17
CXCL9	-0.28	0.56	-10000	0	-1.2	121	121
MPO	-0.18	0.44	-10000	0	-1	72	72
positive regulation of humoral immune response	-0.21	0.51	-10000	0	-1.1	92	92
IL23/IL23R/JAK2/TYK2	-0.23	0.54	-10000	0	-1.2	91	91
IL6	-0.27	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	-0.35	10	10
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.012	0.073	8	-10000	0	8
CD3E	-0.18	0.44	-10000	0	-1	71	71
keratinocyte proliferation	-0.21	0.51	-10000	0	-1.1	92	92
NOS2	-0.18	0.44	-10000	0	-0.96	93	93

×

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	-0.014	0.11	-10000	0	-0.38	42	42
GNB1/GNG2	-0.058	0.077	-10000	0	-0.18	139	139
AKT1	-0.024	0.12	-10000	0	-0.22	60	60
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+	-0.049	0.17	-10000	0	-0.29	142	142
LYN	0.029	0.062	-10000	0	-0.29	5	5
RhoA/GTP	-0.041	0.056	-10000	0	-0.13	79	79
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.067	0.19	-10000	0	-0.35	143	143
GNG2	0.016	0.029	-10000	0	-0.35	3	3
ARRB2	0.018	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.005	0.1	-10000	0	-0.39	22	22
G beta5/gamma2	-0.076	0.1	-10000	0	-0.24	138	138
PRKCH	-0.063	0.19	-10000	0	-0.35	140	140
DNM1	0.012	0.052	-10000	0	-0.39	8	8
TXA2/TP beta/beta Arrestin3	0.002	0.02	-10000	0	-0.25	1	1
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	-0.002	0.088	-10000	0	-0.35	29	29
G12 family/GTP	-0.097	0.13	-10000	0	-0.3	142	142
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	0.36	18	-10000	0	18
mol:NADP	0.017	0.012	-10000	0	-0.26	1	1
RAB11A	0.016	0.029	-10000	0	-0.35	3	3
PRKG1	0.017	0.012	-10000	0	-0.26	1	1
mol:IP3	-0.068	0.2	-10000	0	-0.37	142	142
cell morphogenesis	0.016	0.05	-10000	0	-0.31	12	12
PLCB2	-0.1	0.26	-10000	0	-0.5	142	142
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	-0.38	12	12
RHOA	0.005	0.08	-10000	0	-0.52	12	12
PTGIR	0.016	0.033	-10000	0	-0.52	2	2
PRKCB1	-0.082	0.22	-10000	0	-0.4	144	144
GNAQ	0	0	-10000	0	-10000	0	0
mol:L-citrulline	0.017	0.012	-10000	0	-0.26	1	1
TXA2/TXA2-R family	-0.11	0.27	-10000	0	-0.52	141	141
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	0.062	-10000	0	-0.56	5	5
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.034	0.044	-10000	0	-0.36	2	2
MAPK14	-0.034	0.13	-10000	0	-0.23	138	138
TGM2/GTP	-0.08	0.23	-10000	0	-0.41	148	148
MAPK11	-0.033	0.14	-10000	0	-0.23	138	138
ARHGEF1	-0.021	0.1	-10000	0	-0.17	138	138
GNAI2	0.006	0.075	-10000	0	-0.48	12	12
JNK cascade	-0.07	0.21	-10000	0	-0.38	141	141
RAB11/GDP	0.016	0.028	-10000	0	-0.34	3	3
ICAM1	-0.053	0.17	-10000	0	-0.3	141	141
cAMP biosynthetic process	-0.063	0.19	-10000	0	-0.34	142	142
Gq family/GTP/EBP50	-0.039	0.11	-10000	0	-0.25	95	95
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	-0.027	0.11	-10000	0	-0.3	41	41
VCAM1	-0.055	0.17	-10000	0	-0.31	145	145
TP beta/Gq family/GDP/G beta5/gamma2	-0.005	0.1	-10000	0	-0.39	22	22
platelet activation	-0.043	0.17	-10000	0	-0.3	141	141
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	-0.006	0.049	-10000	0	-0.54	4	4
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	-0.08	0.22	-10000	0	-0.41	142	142
EGFR	-0.077	0.17	-10000	0	-0.35	136	136
TXA2/TP alpha	-0.092	0.25	-10000	0	-0.46	140	140
Gq family/GTP	-0.039	0.079	-10000	0	-0.24	60	60
YES1	0.026	0.07	-10000	0	-0.34	6	6
GNAI2/GTP	-0.015	0.055	-10000	0	-0.33	5	5
PGD2/DP	-0.001	0.063	-10000	0	-0.24	29	29
SLC9A3R1	-0.044	0.16	-10000	0	-0.44	71	71
FYN	0.027	0.072	-10000	0	-0.33	10	10
mol:NO	0.017	0.012	-10000	0	-0.26	1	1
GNA15	0.001	0.078	-10000	0	-0.33	25	25
PGK/cGMP	0.023	0.01	-10000	0	-10000	0	0
RhoA/GDP	0.006	0.079	-10000	0	-0.51	12	12
TP alpha/TGM2/GDP/G beta/gamma	0.029	0.076	-10000	0	-0.36	6	6
NOS3	0.017	0.012	-10000	0	-0.26	1	1
RAC1	0.018	0	-10000	0	-10000	0	0
PRKCA	-0.062	0.19	-10000	0	-0.34	140	140
PRKCB	-0.065	0.19	-10000	0	-0.35	142	142
PRKCE	-0.063	0.19	-10000	0	-0.35	140	140
PRKCD	-0.069	0.2	-10000	0	-0.37	141	141
PRKCG	-0.07	0.2	-10000	0	-0.37	141	141
muscle contraction	-0.097	0.25	-10000	0	-0.48	141	141
PRKCZ	-0.061	0.18	-10000	0	-0.34	141	141
ARR3	0.017	0.012	-10000	0	-0.26	1	1
TXA2/TP beta	0.028	0.059	-10000	0	-0.31	2	2
PRKCQ	-0.069	0.2	-10000	0	-0.35	146	146
MAPKKK cascade	-0.087	0.23	-10000	0	-0.44	142	142
SELE	-0.078	0.2	-10000	0	-0.38	145	145
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	-0.081	0.18	-10000	0	-0.35	141	141
chemotaxis	-0.13	0.31	-10000	0	-0.6	140	140
GNA12	0.018	0	-10000	0	-10000	0	0
GNA13	0.009	0.059	-10000	0	-0.38	11	11
GNA11	0.014	0.047	-10000	0	-0.52	4	4
Rac1/GTP	0.013	0.002	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.099	0.25	-10000	0	-0.62	80	80
IHH	-0.013	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	-0.053	0.17	-10000	0	-0.47	47	47
SMO	-0.064	0.18	-10000	0	-0.46	58	58
AKT1	-0.027	0.13	-10000	0	-0.52	21	21
ARRB2	0.018	0	-10000	0	-10000	0	0
BOC	-0.018	0.12	-10000	0	-0.38	48	48
ADRBK1	0.018	0	-10000	0	-10000	0	0
heart looping	-0.063	0.18	-10000	0	-0.46	58	58
STIL	-0.052	0.15	-10000	0	-0.36	56	56
DHH N/PTCH2	0.026	0	-10000	0	-10000	0	0
DHH N/PTCH1	-0.027	0.13	-10000	0	-0.37	23	23
PIK3CA	0.016	0.029	-10000	0	-0.35	3	3
DHH	0.018	0	-10000	0	-10000	0	0
PTHLH	-0.12	0.31	-10000	0	-0.76	79	79
determination of left/right symmetry	-0.063	0.18	-10000	0	-0.46	58	58
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
skeletal system development	-0.12	0.3	-10000	0	-0.75	79	79
IHH N/Hhip	0.004	0.069	-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	-0.063	0.18	-10000	0	-0.46	58	58
pancreas development	0.01	0.052	-10000	0	-0.33	11	11
HHAT	-0.045	0.17	-10000	0	-0.51	63	63
PI3K	0.006	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	-0.063	0.18	-10000	0	-0.46	58	58
SHH Np/Cholesterol/PTCH1	-0.048	0.14	-10000	0	-0.36	48	48
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	74	74
SMO/Vitamin D3	-0.06	0.16	-10000	0	-0.4	64	64
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	-0.45	97	97
SHH Np/Cholesterol/BOC	-0.026	0.12	-10000	0	-0.28	83	83
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	-0.046	0.14	-10000	0	-0.36	48	48
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	74	74
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	-0.042	0.14	-10000	0	-0.33	74	74
HHIP	0.01	0.052	-10000	0	-0.33	11	11

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.011	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	0.015	0.024	-10000	0	-0.26	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	165	165
GNAI2	0.006	0.075	-10000	0	-0.48	12	12
GNAI3	0.017	0.023	-10000	0	-0.52	1	1
GNAI1	-0.015	0.12	-10000	0	-0.38	44	44
mol:GDP	-0.088	0.17	-10000	0	-0.41	109	109
cell proliferation	-0.066	0.18	-10000	0	-0.41	82	82
PIK3CA	0.016	0.029	-10000	0	-0.35	3	3
FOS	-0.13	0.29	-10000	0	-0.8	76	76
mol:Ca2+	-0.014	0.022	-10000	0	-0.083	22	22
MAPK3	-0.05	0.14	-10000	0	-0.41	34	34
MAPK1	-0.029	0.092	-10000	0	-0.27	26	26
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
mol:IP3	-0.001	0.002	-10000	0	-0.003	171	171
cAMP biosynthetic process	0.013	0.021	-10000	0	-10000	0	0
GNG2	0.016	0.029	-10000	0	-0.35	3	3
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.003	171	171
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	-0.44	3	3
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.003	171	171
PI3K	0.007	0.07	-10000	0	-0.31	21	21
apoptosis	0.063	0.17	0.41	83	-10000	0	83
T-DHT/AR/PELP1	-0.044	0.13	-10000	0	-0.31	104	104
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	-0.031	0.12	-10000	0	-0.24	120	120
GNAZ	0.002	0.085	-10000	0	-0.43	18	18
SHBG	0.018	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.002	0.11	-10000	0	-0.45	16	16
mol:T-DHT	0	0.001	0.002	1	-0.003	51	52
RAC1	0.018	0	-10000	0	-10000	0	0
GNRH1	0	0.06	-10000	0	-0.24	27	27
Gi family/GTP	-0.022	0.094	-10000	0	-0.3	20	20
CDC42	0.018	0	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.049	0.17	-9999	-0.44	78	78
PLK4	0.008	0.065	-9999	-0.38	13	13
regulation of centriole replication	-0.03	0.13	-9999	-0.37	59	59

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	71	71

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.065	0.12	-9999	-0.32	61	61
SMAD6-7/SMURF1	0.034	0.021	-9999	-0.3	1	1
NOG	0.009	0.056	-9999	-0.31	14	14
SMAD9	-0.021	0.11	-9999	-0.62	11	11
SMAD4	0.009	0.067	-9999	-0.49	9	9
SMAD5	-0.063	0.14	-9999	-0.41	45	45
BMP7/USAG1	-0.19	0.19	-9999	-0.39	205	205
SMAD5/SKI	-0.052	0.14	-9999	-0.4	41	41
SMAD1	0.024	0.061	-9999	-0.37	7	7
BMP2	-0.018	0.11	-9999	-0.32	57	57
SMAD1/SMAD1/SMAD4	-0.01	0.044	-9999	-0.33	3	3
BMPR1A	0.01	0.064	-9999	-0.46	9	9
BMPR1B	-0.11	0.16	-9999	-0.3	218	218
BMPR1A-1B/BAMBI	-0.13	0.17	-9999	-0.37	156	156
AHSG	0.016	0.024	-9999	-0.26	4	4
CER1	0.017	0.012	-9999	-0.26	1	1
BMP2-4/CER1	-0.052	0.14	-9999	-0.34	84	84
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.054	0.14	-9999	-0.39	42	42
BMP2-4 (homodimer)	-0.075	0.16	-9999	-0.41	83	83
RGMB	0.008	0.073	-9999	-0.52	10	10
BMP6/BMPR2/BMPR1A-1B	-0.043	0.11	-9999	-0.3	52	52
RGMA	-0.027	0.12	-9999	-0.3	74	74
SMURF1	0.018	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.073	0.14	-9999	-0.32	98	98
BMP2-4/USAG1	-0.2	0.2	-9999	-0.38	249	249
SMAD6/SMURF1/SMAD5	-0.051	0.14	-9999	-0.41	36	36
SOSTDC1	-0.23	0.23	-9999	-0.4	314	314
BMP7/BMPR2/BMPR1A-1B	-0.062	0.12	-9999	-0.3	67	67
SKI	0.017	0.017	-9999	-0.26	2	2
BMP6 (homodimer)	-0.006	0.089	-9999	-0.3	39	39
HFE2	0.004	0.08	-9999	-0.45	15	15
ZFYVE16	0.015	0.04	-9999	-0.52	3	3
MAP3K7	0.016	0.021	-9999	-0.26	3	3
BMP2-4/CHRD	-0.059	0.16	-9999	-0.37	84	84
SMAD5/SMAD5/SMAD4	-0.056	0.14	-9999	-0.41	39	39
MAPK1	0.016	0.033	-9999	-0.52	2	2
TAK1/TAB family	-0.032	0.13	-9999	-0.44	24	24
BMP7 (homodimer)	-0.042	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	-0.26	4	4
CTDSP2	0.014	0.044	-9999	-0.42	5	5
BMP2-4/FETUA	-0.053	0.14	-9999	-0.34	84	84
MAP3K7IP1	0.018	0	-9999	-10000	0	0
GREM1	-0.038	0.16	-9999	-0.46	62	62
BMPR2 (homodimer)	0.016	0.033	-9999	-0.52	2	2
GADD34/PP1CA	0.029	0.042	-9999	-0.3	6	6
BMPR1A-1B (homodimer)	-0.069	0.12	-9999	-0.2	223	223
CHRDL1	-0.013	0.091	-9999	-0.27	56	56
ENDOFIN/SMAD1	0.031	0.065	-9999	-0.36	8	8
SMAD6-7/SMURF1/SMAD1	0.046	0.058	-9999	-0.37	3	3
SMAD6/SMURF1	0.018	0	-9999	-10000	0	0
BAMBI	-0.13	0.22	-9999	-0.41	185	185
SMURF2	0.009	0.058	-9999	-0.34	13	13
BMP2-4/CHRDL1	-0.068	0.16	-9999	-0.35	97	97
BMP2-4/GREM1	-0.085	0.17	-9999	-0.37	120	120
SMAD7	0.016	0.026	-9999	-0.39	2	2
SMAD8A/SMAD8A/SMAD4	-0.015	0.11	-9999	-0.52	14	14
SMAD1/SMAD6	0.033	0.059	-9999	-0.34	7	7
TAK1/SMAD6	0.025	0.014	-9999	-10000	0	0
BMP7	-0.042	0.13	-9999	-0.29	101	101
BMP6	-0.006	0.089	-9999	-0.3	39	39
MAP3K7IP2	0.014	0.047	-9999	-0.52	4	4
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.052	0.13	-9999	-0.37	39	39
PPM1A	0.016	0.026	-9999	-0.39	2	2
SMAD1/SMURF2	0.029	0.067	-9999	-0.35	8	8
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	-0.31	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	-0.35	3	3
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.081	0.15	-9999	-0.35	89	89
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	-0.075	0.15	-9999	-0.33	98	98
BMP4	-0.092	0.19	-9999	-0.39	143	143
FST	-0.015	0.1	-9999	-0.31	52	52
BMP2-4/NOG	-0.056	0.15	-9999	-0.35	88	88
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.049	0.11	-9999	-0.3	52	52

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.027	0.13	-10000	0	-0.26	111	111
epithelial cell differentiation	-0.007	0.1	-10000	0	-0.26	76	76
CYFIP2	-0.042	0.16	-10000	0	-0.46	65	65
ENAH	0.012	0.097	-10000	0	-0.32	12	12
EGFR	-0.077	0.17	-10000	0	-0.35	136	136
EPHA2	0.008	0.06	-10000	0	-0.33	14	14
MYO6	-0.013	0.11	-10000	0	-0.25	92	92
CTNNB1	0.001	0.09	-10000	0	-0.45	19	19
ABI1/Sra1/Nap1	-0.003	0.1	-10000	0	-0.31	52	52
AQP5	-0.086	0.19	-10000	0	-0.45	97	97
CTNND1	0.016	0.029	-10000	0	-0.35	3	3
mol:PI-4-5-P2	-0.005	0.1	-10000	0	-0.24	78	78
regulation of calcium-dependent cell-cell adhesion	-0.015	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	-0.089	0.2	-10000	0	-0.47	97	97
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	-0.005	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	-0.007	0.12	-10000	0	-0.45	14	14
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	71	71
EGFR/EGFR/EGF/EGF	-0.13	0.14	-10000	0	-0.38	92	92
RhoA/GDP	-0.01	0.11	-10000	0	-0.25	85	85
actin cytoskeleton organization	-0.008	0.11	-10000	0	-0.38	7	7
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	0.21	-10000	0	-0.42	146	146
DIAPH1	-0.054	0.18	-10000	0	-0.58	52	52
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	-0.008	0.11	-10000	0	-0.4	7	7
EFNA1	0	0.094	-10000	0	-0.49	18	18
LPP	-0.004	0.1	-10000	0	-0.4	7	7
Ephrin A1/EPHA2	-0.045	0.094	-10000	0	-0.43	8	8
SEC6/SEC8	-0.045	0.092	-10000	0	-0.41	10	10
MGAT3	-0.015	0.11	-10000	0	-0.25	82	82
HGF/MET	-0.044	0.089	-10000	0	-0.34	10	10
HGF	0.008	0.069	-10000	0	-0.45	11	11
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.028	0.13	-10000	0	-0.26	111	111
actin cable formation	0.017	0.1	-10000	0	-0.3	15	15
KIAA1543	0.001	0.1	-10000	0	-0.35	9	9
KIFC3	-0.005	0.1	-10000	0	-0.24	77	77
NCK1	0.011	0.046	-10000	0	-0.28	12	12
EXOC3	0.017	0.012	-10000	0	-0.26	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	-0.005	0.1	-10000	0	-0.24	78	78
LIMA1	-0.025	0.15	-10000	0	-0.52	42	42
ABI1	0.016	0.021	-10000	0	-0.26	3	3
ROCK1	0.009	0.1	-10000	0	-0.36	10	10
adherens junction assembly	0.012	0.1	-10000	0	-0.38	10	10
IGF-1R heterotetramer/IGF1	-0.12	0.16	-10000	0	-0.43	73	73
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	-0.001	0.078	-10000	0	-0.3	31	31
PLEKHA7	-0.003	0.099	-10000	0	-0.24	77	77
mol:GTP	0.024	0.071	-10000	0	-0.27	24	24
establishment of epithelial cell apical/basal polarity	0.005	0.11	-10000	0	-0.41	10	10
cortical actin cytoskeleton stabilization	-0.027	0.13	-10000	0	-0.26	111	111
regulation of cell-cell adhesion	-0.008	0.11	-10000	0	-0.38	7	7
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.028	0.13	-10000	0	-0.26	111	111

×

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	-0.04	0.18	-9999	-0.51	64	64
Syndecan-4/Syndesmos	-0.043	0.2	-9999	-0.51	71	71
positive regulation of JNK cascade	-0.072	0.22	-9999	-0.5	88	88
Syndecan-4/ADAM12	-0.069	0.24	-9999	-0.54	93	93
CCL5	-0.05	0.18	-9999	-0.49	70	70
Rac1/GDP	0.013	0	-9999	-10000	0	0
DNM2	0.017	0.012	-9999	-0.26	1	1
ITGA5	0.014	0.042	-9999	-0.46	4	4
SDCBP	0.003	0.081	-9999	-0.4	19	19
PLG	0.016	0.033	-9999	-0.51	2	2
ADAM12	-0.049	0.17	-9999	-0.47	72	72
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	-0.04	0.2	-9999	-0.51	71	71
Syndecan-4/CXCL12/CXCR4	-0.076	0.24	-9999	-0.54	88	88
Syndecan-4/Laminin alpha3	-0.079	0.22	-9999	-0.54	77	77
MDK	-0.016	0.12	-9999	-0.37	46	46
Syndecan-4/FZD7	-0.07	0.23	-9999	-0.53	84	84
Syndecan-4/Midkine	-0.054	0.21	-9999	-0.52	76	76
FZD7	-0.05	0.16	-9999	-0.4	86	86
Syndecan-4/FGFR1/FGF	-0.073	0.21	-9999	-0.48	87	87
THBS1	-0.025	0.14	-9999	-0.51	43	43
integrin-mediated signaling pathway	-0.062	0.22	-9999	-0.51	84	84
positive regulation of MAPKKK cascade	-0.072	0.22	-9999	-0.5	88	88
Syndecan-4/TACI	-0.041	0.2	-9999	-0.5	72	72
CXCR4	-0.028	0.14	-9999	-0.42	55	55
cell adhesion	-0.006	0.1	-9999	-0.29	54	54
Syndecan-4/Dynamin	-0.039	0.2	-9999	-0.5	71	71
Syndecan-4/TSP1	-0.059	0.22	-9999	-0.52	81	81
Syndecan-4/GIPC	-0.041	0.2	-9999	-0.5	71	71
Syndecan-4/RANTES	-0.071	0.23	-9999	-0.54	78	78
ITGB1	0.015	0.037	-9999	-0.39	4	4
LAMA1	0.015	0.027	-9999	-0.26	5	5
LAMA3	-0.069	0.18	-9999	-0.43	102	102
RAC1	0.018	0	-9999	-10000	0	0
PRKCA	0.017	0.05	-9999	-0.25	6	6
Syndecan-4/alpha-Actinin	-0.045	0.21	-9999	-0.52	73	73
TFPI	0.005	0.061	-9999	-0.27	24	24
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	-0.071	0.22	-9999	-0.52	77	77
ACTN1	0.005	0.079	-9999	-0.48	13	13
TNC	-0.04	0.15	-9999	-0.36	81	81
Syndecan-4/CXCL12	-0.066	0.23	-9999	-0.53	82	82
FGF6	0.009	0.067	-9999	-0.49	9	9
RHOA	0.005	0.08	-9999	-0.52	12	12
CXCL12	-0.041	0.16	-9999	-0.46	64	64
TNFRSF13B	0.013	0.036	-9999	-0.26	9	9
FGF2	-0.064	0.16	-9999	-0.34	121	121
FGFR1	-0.011	0.1	-9999	-0.35	42	42
Syndecan-4/PI-4-5-P2	-0.05	0.2	-9999	-0.51	71	71
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.045	0.16	-9999	-0.45	71	71
cell migration	0.001	0.008	-9999	-10000	0	0
PRKCD	0.015	0.041	-9999	-0.44	4	4
vasculogenesis	-0.056	0.21	-9999	-0.5	81	81
SDC4	-0.052	0.22	-9999	-0.54	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	-0.046	0.21	-9999	-0.51	73	73
MMP9	-0.04	0.17	-9999	-0.5	60	60
Rac1/GTP	-0.007	0.1	-9999	-0.3	54	54
cytoskeleton organization	-0.04	0.2	-9999	-0.49	71	71
GIPC1	0.014	0.042	-9999	-0.46	4	4
Syndecan-4/TFPI	-0.045	0.2	-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	0.009	0.063	-10000	0	-0.4	11	11
EGFR	-0.077	0.17	-10000	0	-0.35	136	136
PRL	0.015	0.031	-10000	0	-0.32	4	4
neuron projection morphogenesis	-0.033	0.22	-10000	0	-0.72	45	45
PTPRZ1	-0.027	0.11	-10000	0	-0.29	78	78
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.048	0.25	-10000	0	-0.82	45	45
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.081	0.28	-10000	0	-0.91	47	47
ADAM17	0.017	0.037	-10000	0	-0.26	4	4
ErbB4/ErbB4	-0.11	0.32	-10000	0	-1	52	52
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.1	0.3	-10000	0	-0.88	57	57
NCOR1	0.016	0.033	-10000	0	-0.52	2	2
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.073	0.27	-10000	0	-0.86	48	48
GRIN2B	-0.074	0.26	-10000	0	-0.81	48	48
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	0.006	0.069	-10000	0	-0.35	17	17
PRLR	-0.03	0.15	-10000	0	-0.49	50	50
E4ICDs/ETO2	-0.17	0.34	-10000	0	-0.8	89	89
axon guidance	-0.08	0.28	-10000	0	-0.88	50	50
NEDD4	0.002	0.099	-10000	0	-0.53	16	16
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	-0.092	0.27	-10000	0	-0.81	55	55
MAPK3	-0.04	0.23	-10000	0	-0.75	45	45
STAT1 (dimer)	-0.11	0.3	-10000	0	-0.87	59	59
MAPK1	-0.041	0.23	-10000	0	-0.75	45	45
JAK2	0.01	0.054	-10000	0	-0.32	12	12
ErbB4/ErbB2/neuregulin 1 beta	-0.091	0.27	-10000	0	-0.83	53	53
NRG1	0.019	0.044	-10000	0	-0.26	5	5
NRG3	0	0.082	-10000	0	-0.34	27	27
NRG2	-0.016	0.1	-10000	0	-0.3	57	57
NRG4	0.009	0.051	-10000	0	-0.27	16	16
heart development	-0.08	0.28	-10000	0	-0.88	50	50
neural crest cell migration	-0.089	0.27	-10000	0	-0.81	53	53
ERBB2	-0.007	0.088	-10000	0	-0.32	22	22
WWOX/E4ICDs	-0.1	0.3	-10000	0	-0.88	55	55
SHC1	0.017	0.023	-10000	0	-0.52	1	1
ErbB4/EGFR/neuregulin 4	-0.13	0.31	-10000	0	-0.79	71	71
apoptosis	0.099	0.28	0.8	60	-10000	0	60
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	-0.76	62	62
ErbB4/ErbB4/betacellulin/betacellulin	-0.13	0.31	-10000	0	-0.87	62	62
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.089	0.29	-10000	0	-0.72	74	74
MDM2	-0.097	0.3	-10000	0	-0.89	55	55
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.063	0.25	-10000	0	-0.84	45	45
STAT5A	-0.072	0.27	-10000	0	-0.84	50	50
ErbB4/EGFR/neuregulin 1 beta	-0.11	0.29	-10000	0	-0.78	63	63
DLG4	0.018	0	-10000	0	-10000	0	0
GRB2/SHC	0.024	0.024	-10000	0	-0.37	1	1
E4ICDs/TAB2/NCoR1	-0.082	0.28	-10000	0	-0.85	54	54
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	-0.052	0.17	-10000	0	-0.42	84	84
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.081	0.28	-10000	0	-0.9	50	50
ERBB4	-0.11	0.32	-10000	0	-1	52	52
STAT5B	0.016	0.026	-10000	0	-0.39	2	2
YAP1	-0.015	0.1	-10000	0	-0.71	6	6
GRB2	0.016	0.024	-10000	0	-0.26	4	4
ErbB4/ErbB2/neuregulin 4	-0.09	0.27	-10000	0	-0.83	53	53
glial cell differentiation	0.081	0.28	0.84	54	-10000	0	54
WWOX	-0.003	0.073	-10000	0	-0.26	40	40
cell proliferation	-0.1	0.27	-10000	0	-0.72	68	68

×

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	-0.006	0.1	-10000	0	-0.39	31	31
EPHB2	0.008	0.062	-10000	0	-0.32	16	16
EFNB1	0.017	0.053	-10000	0	-0.39	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.02	0.084	-10000	0	-0.33	12	12
Ephrin B2/EPHB1-2	-0.005	0.088	-10000	0	-0.28	32	32
neuron projection morphogenesis	-0.024	0.063	-10000	0	-0.29	17	17
Ephrin B1/EPHB1-2/Tiam1	0.013	0.09	-10000	0	-0.3	25	25
DNM1	0.012	0.052	-10000	0	-0.39	8	8
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.084	0.23	-10000	0	-0.59	84	84
YES1	-0.13	0.3	-10000	0	-0.84	81	81
Ephrin B1/EPHB1-2/NCK2	0.018	0.081	-10000	0	-0.3	17	17
PI3K	-0.081	0.23	-10000	0	-0.59	87	87
mol:GDP	0.012	0.088	-10000	0	-0.29	25	25
ITGA2B	0.016	0.021	-10000	0	-0.26	3	3
endothelial cell proliferation	-0.007	0.096	-10000	0	-0.34	35	35
FYN	-0.13	0.3	-10000	0	-0.83	81	81
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	32	32
RGS3	0.017	0.012	-10000	0	-0.26	1	1
cell adhesion	-0.069	0.22	-10000	0	-0.56	82	82
LYN	-0.12	0.3	-10000	0	-0.82	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	0.076	-10000	0	-0.32	25	25
EPHB1	-0.023	0.11	-10000	0	-0.28	73	73
EPHB4	-0.01	0.11	-10000	0	-0.42	33	33
RAC1	0.018	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.007	0.096	-10000	0	-0.34	35	35
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	81	81
regulation of stress fiber formation	-0.017	0.08	0.29	17	-10000	0	17
MAPK8	-0.074	0.22	-10000	0	-0.56	82	82
Ephrin B1/EPHB1-2/RGS3	0.019	0.078	-10000	0	-0.29	15	15
endothelial cell migration	-0.088	0.21	-10000	0	-0.52	94	94
NCK2	0.015	0.027	-10000	0	-0.26	5	5
PTPN13	-0.089	0.24	-10000	0	-0.62	85	85
regulation of focal adhesion formation	-0.017	0.08	0.29	17	-10000	0	17
chemotaxis	-0.018	0.077	0.29	15	-10000	0	15
PIK3CA	0.016	0.029	-10000	0	-0.35	3	3
Rac1/GTP	0.014	0.08	-10000	0	-0.3	16	16
angiogenesis	-0.11	0.24	-10000	0	-0.68	81	81
LCK	-0.14	0.31	-10000	0	-0.84	81	81

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.007	0.078	-9999	-0.24	45	45
NF kappa B1 p50/RelA/I kappa B alpha	0.003	0.086	-9999	-0.27	23	23
AP1	-0.091	0.14	-9999	-0.3	131	131
mol:PIP3	-0.065	0.11	-9999	-0.28	84	84
AKT1	0.008	0.11	-9999	-0.37	22	22
PTK2B	-0.008	0.063	-9999	-0.2	44	44
RHOA	-0.006	0.092	-9999	-0.42	16	16
PIK3CB	0.012	0.055	-9999	-0.44	7	7
mol:Ca2+	-0.024	0.094	-9999	-0.26	60	60
MAGI3	-0.014	0.12	-9999	-0.46	35	35
RELA	0.018	0	-9999	-10000	0	0
apoptosis	-0.003	0.065	-9999	-0.22	41	41
HRAS/GDP	0.009	0.037	-9999	-0.29	7	7
positive regulation of microtubule depolymerization	-0.044	0.12	-9999	-0.26	117	117
NF kappa B1 p50/RelA	-0.039	0.092	-9999	-0.27	46	46
endothelial cell migration	-0.032	0.17	-9999	-0.55	51	51
ADCY4	-0.004	0.11	-9999	-0.31	45	45
ADCY5	-0.012	0.11	-9999	-0.31	45	45
ADCY6	-0.002	0.1	-9999	-0.29	44	44
ADCY7	-0.006	0.11	-9999	-0.32	44	44
ADCY1	-0.001	0.1	-9999	-0.29	44	44
ADCY2	-0.023	0.12	-9999	-0.34	48	48
ADCY3	-0.004	0.1	-9999	-0.29	46	46
ADCY8	-0.003	0.1	-9999	-0.29	44	44
ADCY9	-0.009	0.11	-9999	-0.3	45	45
GSK3B	-0.001	0.06	-9999	-0.18	42	42
arachidonic acid secretion	0.003	0.1	-9999	-0.3	38	38
GNG2	0.016	0.029	-9999	-0.34	3	3
TRIP6	0	0.088	-9999	-0.4	23	23
GNAO1	-0.003	0.076	-9999	-0.25	41	41
HRAS	0.012	0.051	-9999	-0.41	7	7
NFKBIA	-0.013	0.091	-9999	-0.25	41	41
GAB1	0.006	0.074	-9999	-0.43	14	14
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0.008	0.15	-9999	-0.89	14	14
JUN	-0.034	0.15	-9999	-0.46	57	57
LPA/LPA2/NHERF2	-0.023	0.099	-9999	-0.3	52	52
TIAM1	-0.023	0.17	-9999	-1	14	14
PIK3R1	-0.009	0.11	-9999	-0.42	32	32
mol:IP3	-0.025	0.095	-9999	-0.26	60	60
PLCB3	-0.015	0.094	-9999	-0.29	49	49
FOS	-0.11	0.2	-9999	-0.37	171	171
positive regulation of mitosis	0.003	0.1	-9999	-0.3	38	38
LPA/LPA1-2-3	-0.013	0.066	-9999	-0.21	51	51
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.017	0.012	-9999	-0.26	1	1
stress fiber formation	0.002	0.062	-9999	-0.19	42	42
GNAZ	-0.011	0.092	-9999	-0.28	52	52
EGFR/PI3K-beta/Gab1	-0.067	0.11	-9999	-0.29	84	84
positive regulation of dendritic cell cytokine production	-0.013	0.066	-9999	-0.21	51	51
LPA/LPA2/MAGI-3	-0.013	0.08	-9999	-0.28	35	35
ARHGEF1	0.01	0.073	-9999	-0.22	44	44
GNAI2	-0.008	0.094	-9999	-0.29	46	46
GNAI3	-0.002	0.076	-9999	-0.25	42	42
GNAI1	-0.021	0.11	-9999	-0.31	55	55
LPA/LPA3	-0.01	0.032	-9999	-0.1	51	51
LPA/LPA2	-0.01	0.032	-9999	-0.1	51	51
LPA/LPA1	-0.017	0.088	-9999	-0.28	51	51
HB-EGF/EGFR	-0.068	0.15	-9999	-0.34	102	102
HBEGF	-0.026	0.13	-9999	-0.38	63	63
mol:DAG	-0.025	0.095	-9999	-0.26	60	60
cAMP biosynthetic process	-0.005	0.11	-9999	-0.3	48	48
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	-0.28	26	26
GNAQ	-0.005	0.026	-9999	-0.081	51	51
LPAR2	0	0.001	-9999	-10000	0	0
LPAR3	0	0.001	-9999	-10000	0	0
LPAR1	-0.011	0.051	-9999	-0.16	51	51
IL8	-0.13	0.19	-9999	-0.4	125	125
PTK2	-0.001	0.065	-9999	-0.21	42	42
Rac1/GDP	0.013	0	-9999	-10000	0	0
CASP3	-0.003	0.066	-9999	-0.22	41	41
EGFR	-0.077	0.17	-9999	-0.35	136	136
PLCG1	-0.014	0.056	-9999	-0.14	66	66
PLD2	-0.003	0.069	-9999	-0.22	45	45
G12/G13	0.006	0.079	-9999	-0.24	44	44
PI3K-beta	-0.039	0.098	-9999	-0.36	30	30
cell migration	0.017	0.061	-9999	-0.25	16	16
SLC9A3R2	-0.032	0.15	-9999	-0.49	52	52
PXN	0.002	0.062	-9999	-0.2	42	42
HRAS/GTP	0.002	0.1	-9999	-0.3	38	38
RAC1	0.018	0	-9999	-10000	0	0
MMP9	-0.042	0.17	-9999	-0.51	60	60
PRKCE	0.011	0.056	-9999	-0.42	8	8
PRKCD	-0.019	0.093	-9999	-0.26	56	56
Gi(beta/gamma)	0.002	0.1	-9999	-0.31	36	36
mol:LPA	-0.011	0.051	-9999	-0.16	51	51
TRIP6/p130 Cas/FAK1/Paxillin	0.013	0.084	-9999	-0.32	16	16
MAPKKK cascade	0.003	0.1	-9999	-0.3	38	38
contractile ring contraction involved in cytokinesis	-0.006	0.091	-9999	-0.42	16	16
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.043	0.097	-9999	-0.18	141	141
GNA15	-0.003	0.052	-9999	-0.29	10	10
GNA12	0.018	0	-9999	-10000	0	0
GNA13	0.009	0.059	-9999	-0.38	11	11
MAPT	-0.046	0.13	-9999	-0.27	117	117
GNA11	0.003	0.038	-9999	-0.3	4	4
Rac1/GTP	0.007	0.16	-9999	-0.94	14	14
MMP2	-0.032	0.18	-9999	-0.55	51	51

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	-0.027	0.15	-9999	-0.4	60	60
alphaM/beta2 Integrin/GPIbA	-0.01	0.11	-9999	-0.34	39	39
alphaM/beta2 Integrin/proMMP-9	-0.036	0.15	-9999	-0.36	79	79
PLAUR	-0.017	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	31	31
AGER	0.01	0.031	-9999	-0.4	2	2
RAP1A	0.011	0.062	-9999	-0.52	7	7
SELPLG	-0.003	0.098	-9999	-0.43	24	24
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.013	0.13	-9999	-0.44	22	22
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.042	0.17	-9999	-0.51	60	60
CYR61	-0.04	0.16	-9999	-0.42	70	70
TLN1	0.017	0.023	-9999	-0.52	1	1
Rap1/GTP	-0.037	0.1	-9999	-0.42	26	26
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	-0.038	0.16	-9999	-0.51	56	56
leukocyte activation during inflammatory response	0.007	0.087	-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	-0.029	0.15	-9999	-0.47	51	51
JAM3	-0.005	0.11	-9999	-0.5	23	23
GP1BA	-0.002	0.07	-9999	-0.26	37	37
alphaM/beta2 Integrin/CTGF	-0.03	0.14	-9999	-0.4	56	56
alphaM/beta2 Integrin	-0.008	0.13	-9999	-0.46	26	26
JAM3 homodimer	-0.005	0.11	-9999	-0.5	23	23
ICAM2	0.007	0.068	-9999	-0.4	13	13
ICAM1	-0.021	0.13	-9999	-0.4	49	49
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.008	0.13	-9999	-0.45	26	26
cell adhesion	-0.011	0.11	-9999	-0.34	39	39
NFKB1	-0.033	0.17	-9999	-0.53	26	26
THY1	-0.005	0.11	-9999	-0.5	23	23
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	-0.048	0.14	-9999	-0.32	91	91
IL6	-0.088	0.27	-9999	-0.71	72	72
ITGB2	-0.022	0.12	-9999	-0.43	40	40
elevation of cytosolic calcium ion concentration	-0.043	0.18	-9999	-0.42	77	77
alphaM/beta2 Integrin/JAM2/JAM3	-0.02	0.15	-9999	-0.38	63	63
JAM2	-0.019	0.13	-9999	-0.44	43	43
alphaM/beta2 Integrin/ICAM1	-0.029	0.16	-9999	-0.33	91	91
alphaM/beta2 Integrin/uPA/Plg	-0.026	0.14	-9999	-0.34	73	73
RhoA/GTP	-0.008	0.14	-9999	-0.44	29	29
positive regulation of phagocytosis	-0.008	0.16	-9999	-0.5	35	35
Ron/MSP	-0.016	0.12	-9999	-0.37	54	54
alphaM/beta2 Integrin/uPAR/uPA	-0.043	0.18	-9999	-0.42	77	77
alphaM/beta2 Integrin/uPAR	-0.02	0.14	-9999	-0.4	51	51
PLAU	-0.05	0.17	-9999	-0.43	81	81
PLAT	-0.092	0.19	-9999	-0.37	148	148
actin filament polymerization	-0.002	0.13	-9999	-0.42	25	25
MST1	0.016	0.021	-9999	-0.26	3	3
alphaM/beta2 Integrin/lipoprotein(a)	0.01	0.089	-9999	-0.31	30	30
TNF	-0.035	0.19	-9999	-0.65	28	28
RAP1B	0.013	0.044	-9999	-0.32	8	8
alphaM/beta2 Integrin/uPA	-0.04	0.15	-9999	-0.38	71	71
fibrinolysis	-0.027	0.14	-9999	-0.34	73	73
HCK	-0.005	0.11	-9999	-0.47	25	25
dendritic cell antigen processing and presentation	-0.008	0.13	-9999	-0.45	26	26
VTN	0.016	0.021	-9999	-0.26	3	3
alphaM/beta2 Integrin/CYR61	-0.034	0.14	-9999	-0.37	67	67
LPA	0.016	0.026	-9999	-0.39	2	2
LRP1	0.017	0.023	-9999	-0.52	1	1
cell migration	-0.05	0.17	-9999	-0.36	104	104
FN1	-0.046	0.17	-9999	-0.46	71	71
alphaM/beta2 Integrin/Thy1	-0.013	0.12	-9999	-0.37	47	47
MPO	0.008	0.051	-9999	-0.26	19	19
KNG1	0.017	0.017	-9999	-0.26	2	2
RAP1/GDP	0.017	0.046	-9999	-0.31	9	9
ROCK1	0	0.13	-9999	-0.47	21	21
ELA2	0.017	0.017	-9999	-0.26	2	2
PLG	0.016	0.033	-9999	-0.52	2	2
CTGF	-0.033	0.15	-9999	-0.42	61	61
alphaM/beta2 Integrin/Hck	-0.012	0.14	-9999	-0.44	40	40
ITGAM	0.002	0.071	-9999	-0.48	10	10
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.073	0.18	-9999	-0.35	131	131
HP	0.013	0.05	-9999	-0.43	6	6
leukocyte adhesion	-0.033	0.18	-9999	-0.54	42	42
SELP	-0.12	0.22	-9999	-0.44	156	156

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.037	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	0.029	0.072	0.24	31	-0.18	13	44
MDM4	0.013	0.044	-10000	0	-0.32	8	8

×

Caspase cascade in apoptosis

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
TOP1	-0.002	0.11	0.22	3	-0.26	49	52
ACTA1	-0.03	0.14	0.24	8	-0.35	59	67
NUMA1	-0.005	0.12	0.2	9	-0.26	53	62
SPTAN1	-0.01	0.13	0.24	11	-0.33	54	65
LIMK1	-0.029	0.15	0.23	9	-0.33	76	85
BIRC3	-0.086	0.19	-10000	0	-0.41	129	129
BIRC2	0.016	0.021	-10000	0	-0.26	3	3
BAX	0.016	0.021	-10000	0	-0.26	3	3
CASP10	-0.042	0.14	-10000	0	-0.31	99	99
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	52	61
DIABLO	0.018	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.009	0.13	0.23	11	-0.33	54	65
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.009	0.067	-10000	0	-0.49	9	9
GSN	-0.02	0.14	0.23	9	-0.34	63	72
MADD	0.018	0	-10000	0	-10000	0	0
TFAP2A	-0.009	0.14	-10000	0	-0.56	27	27
BID	-0.022	0.09	-10000	0	-0.2	94	94
MAP3K1	-0.03	0.13	-10000	0	-0.41	44	44
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	-0.34	65	70
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	-0.025	0.17	-10000	0	-0.64	35	35
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.005	0.13	0.24	4	-0.31	51	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	-0.46	4	4
ICAD/CAD	-0.003	0.13	0.25	3	-0.32	49	52
CASP7	0.045	0.12	0.29	68	-0.45	9	77
KRT18	-0.072	0.21	-10000	0	-0.57	77	77
apoptosis	-0.005	0.14	0.26	8	-0.31	54	62
DFFA	-0.01	0.13	0.24	11	-0.33	54	65
DFFB	-0.01	0.13	0.24	11	-0.33	54	65
PARP1	0.02	0.075	0.19	37	-0.3	8	45
actin filament polymerization	0.026	0.15	0.34	60	-0.22	9	69
TNF	-0.004	0.094	-10000	0	-0.36	31	31
CYCS	-0.012	0.062	-10000	0	-0.16	35	35
SATB1	-0.018	0.13	-10000	0	-0.43	28	28
SLK	-0.01	0.13	0.24	11	-0.33	54	65
p15 BID/BAX	-0.011	0.082	-10000	0	-0.28	12	12
CASP2	0.01	0.089	-10000	0	-0.38	11	11
JNK cascade	0.029	0.13	0.41	44	-10000	0	44
CASP3	-0.017	0.14	0.25	11	-0.36	54	65
LMNB2	0.017	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	-0.025	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	-0.33	54	65
GZMB	-0.058	0.16	-10000	0	-0.38	97	97
CASP1	-0.038	0.16	-10000	0	-0.42	60	60
LMNB1	-0.033	0.12	-10000	0	-0.29	38	38
APP	-0.025	0.17	-10000	0	-0.64	35	35
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	0.14	0.22	31	-0.31	55	86
LMNA	0.014	0.076	-10000	0	-0.3	11	11
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.003	0.095	-10000	0	-0.38	13	13
LRDD	0.018	0	-10000	0	-10000	0	0
SREBF1	-0.036	0.15	0.24	10	-0.36	63	73
APAF-1/Caspase 9	0.015	0.068	-10000	0	-0.39	5	5
nuclear fragmentation during apoptosis	-0.005	0.12	0.2	9	-0.26	53	62
CFL2	-0.027	0.15	0.22	9	-0.34	60	69
GAS2	-0.035	0.15	0.24	10	-0.32	78	88
positive regulation of apoptosis	-0.003	0.08	-10000	0	-0.26	21	21
PRF1	-0.009	0.093	-10000	0	-0.31	43	43

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.04	0.15	-9999	-0.38	74	74
EPHB2	0.007	0.062	-9999	-0.32	16	16
Syndecan-2/TACI	-0.006	0.091	-9999	-0.3	37	37
LAMA1	0.015	0.027	-9999	-0.26	5	5
Syndecan-2/alpha2 ITGB1	-0.061	0.17	-9999	-0.31	137	137
HRAS	0.012	0.051	-9999	-0.41	7	7
Syndecan-2/CASK	-0.016	0.088	-9999	-0.31	37	37
ITGA5	0.014	0.042	-9999	-0.46	4	4
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	-0.01	0.093	-9999	-0.28	48	48
LAMA3	-0.069	0.18	-9999	-0.43	102	102
EZR	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.017	0.12	-9999	-0.38	46	46
Syndecan-2/MMP2	-0.03	0.14	-9999	-0.38	62	62
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.023	0.12	-9999	-0.37	56	56
dendrite morphogenesis	-0.009	0.095	-9999	-0.3	41	41
Syndecan-2/GM-CSF	-0.013	0.099	-9999	-0.31	42	42
determination of left/right symmetry	-0.016	0.11	-9999	-0.37	37	37
Syndecan-2/PKC delta	-0.005	0.093	-9999	-0.3	40	40
GNB2L1	0.015	0.04	-9999	-0.52	3	3
MAPK3	-0.004	0.09	-9999	-0.27	43	43
MAPK1	-0.005	0.092	-9999	-0.28	43	43
Syndecan-2/RACK1	0.004	0.087	-9999	-0.26	43	43
NF1	0.015	0.035	-9999	-0.43	3	3
FGFR/FGF/Syndecan-2	-0.016	0.11	-9999	-0.37	37	37
ITGA2	-0.047	0.17	-9999	-0.46	72	72
MAPK8	0.002	0.093	-9999	-0.3	40	40
Syndecan-2/alpha2/beta1 Integrin	-0.017	0.13	-9999	-0.3	82	82
Syndecan-2/Kininogen	-0.004	0.09	-9999	-0.3	37	37
ITGB1	0.015	0.037	-9999	-0.39	4	4
SRC	0.008	0.085	-9999	-0.25	44	44
Syndecan-2/CASK/Protein 4.1	-0.003	0.082	-9999	-0.27	38	38
extracellular matrix organization	-0.004	0.091	-9999	-0.3	38	38
actin cytoskeleton reorganization	-0.04	0.15	-9999	-0.38	74	74
Syndecan-2/Caveolin-2/Ras	-0.013	0.12	-9999	-0.33	53	53
Syndecan-2/Laminin alpha3	-0.055	0.15	-9999	-0.34	98	98
Syndecan-2/RasGAP	0.007	0.093	-9999	-0.25	51	51
alpha5/beta1 Integrin	0.022	0.041	-9999	-0.37	5	5
PRKCD	0.014	0.042	-9999	-0.46	4	4
Syndecan-2 dimer	-0.009	0.095	-9999	-0.3	41	41
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	0.093	-9999	-0.24	52	52
RHOA	0.005	0.08	-9999	-0.52	12	12
SDCBP	0.003	0.081	-9999	-0.4	19	19
TNFRSF13B	0.013	0.036	-9999	-0.26	9	9
RASA1	0.004	0.079	-9999	-0.42	16	16
alpha2/beta1 Integrin	-0.023	0.12	-9999	-0.37	56	56
Syndecan-2/Synbindin	-0.003	0.09	-9999	-0.3	37	37
TGFB1	0.017	0.023	-9999	-0.52	1	1
CASP3	0.004	0.084	-9999	-0.27	40	40
FN1	-0.046	0.17	-9999	-0.46	71	71
Syndecan-2/IL8	-0.055	0.14	-9999	-0.33	86	86
SDC2	-0.016	0.11	-9999	-0.37	37	37
KNG1	0.017	0.017	-9999	-0.26	2	2
Syndecan-2/Neurofibromin	-0.005	0.092	-9999	-0.3	39	39
TRAPPC4	0.018	0	-9999	-10000	0	0
CSF2	-0.001	0.075	-9999	-0.28	33	33
Syndecan-2/TGFB1	-0.004	0.091	-9999	-0.3	38	38
Syndecan-2/Syntenin/PI-4-5-P2	-0.01	0.094	-9999	-0.28	48	48
Syndecan-2/Ezrin	-0.009	0.091	-9999	-0.28	49	49
PRKACA	0.004	0.083	-9999	-0.27	39	39
angiogenesis	-0.055	0.14	-9999	-0.33	86	86
MMP2	-0.029	0.15	-9999	-0.47	51	51
IL8	-0.073	0.17	-9999	-0.34	135	135
calcineurin-NFAT signaling pathway	-0.006	0.091	-9999	-0.3	37	37

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.01	0.065	-9999	-0.37	9	9
alphaV beta3 Integrin	-0.035	0.13	-9999	-0.33	63	63
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	30	30
VEGFA	0	0.076	-9999	-0.29	31	31
ILK	0.002	0.073	-9999	-0.75	2	2
ROCK1	0.018	0	-9999	-10000	0	0
AKT1	0.007	0.075	-9999	-0.49	5	5
PTK2B	0.012	0.092	-9999	-0.32	28	28
alphaV/beta3 Integrin/JAM-A	-0.015	0.12	-9999	-0.28	61	61
CBL	0.017	0.012	-9999	-0.26	1	1
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.009	0.09	-9999	-0.33	29	29
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.11	0.22	-9999	-0.39	170	170
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.02	0.086	-9999	-0.38	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	-0.19	0.24	-9999	-0.54	131	131
PI4 Kinase	0.025	0.024	-9999	-0.37	2	2
PIK3CA	0.016	0.029	-9999	-0.35	3	3
alphaV/beta3 Integrin/Osteopontin	-0.084	0.16	-9999	-0.33	144	144
RPS6KB1	-0.15	0.24	-9999	-0.49	135	135
TLN1	0.017	0.023	-9999	-0.52	1	1
MAPK3	-0.094	0.23	-9999	-0.64	61	61
GPR124	0.001	0.092	-9999	-0.52	16	16
MAPK1	-0.094	0.23	-9999	-0.65	59	59
PXN	0.018	0	-9999	-10000	0	0
PIK3R1	-0.009	0.11	-9999	-0.42	32	32
alphaV/beta3 Integrin/Tumstatin	0.011	0.089	-9999	-0.34	25	25
cell adhesion	-0.01	0.12	-9999	-0.31	59	59
ANGPTL3	0.01	0.061	-9999	-0.43	9	9
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	0.012	0.055	-9999	-0.45	7	7
ITGB3	0.002	0.076	-9999	-0.32	25	25
IGF1	-0.1	0.21	-9999	-0.42	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	-0.003	0.1	-9999	-0.48	22	22
CD47	-0.005	0.11	-9999	-0.47	25	25
alphaV/beta3 Integrin/CD47	-0.001	0.1	-9999	-0.32	43	43
VCL	0.016	0.029	-9999	-0.35	3	3
alphaV/beta3 Integrin/Del1	-0.066	0.17	-9999	-0.36	115	115
CSF1	0.014	0.037	-9999	-0.3	7	7
PIK3C2A	-0.005	0.1	-9999	-0.71	8	8
PI4 Kinase/Pyk2	-0.043	0.093	-9999	-0.39	19	19
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.013	0.1	-9999	-0.34	30	30
FAK1/Vinculin	0.003	0.11	-9999	-0.37	27	27
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	0.021	-9999	-0.26	3	3
BCAR1	0.017	0.012	-9999	-0.26	1	1
FGF2	-0.064	0.16	-9999	-0.34	121	121
F11R	-0.037	0.12	-9999	-0.37	41	41
alphaV/beta3 Integrin/Lactadherin	-0.007	0.12	-9999	-0.39	39	39
alphaV/beta3 Integrin/TGFBR2	0.01	0.093	-9999	-0.36	27	27
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.031	0.063	-9999	-0.27	20	20
HSP90AA1	0.013	0.045	-9999	-0.39	6	6
alphaV/beta3 Integrin/Talin	0.013	0.077	-9999	-0.3	24	24
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.046	0.17	-9999	-0.46	71	71
alphaV/beta3 Integrin/Pyk2	0.017	0.094	-9999	-0.32	28	28
SDC1	-0.037	0.16	-9999	-0.46	61	61
VAV3	-0.024	0.13	-9999	-0.27	103	103
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	26	26
cell migration	0.011	0.1	-9999	-0.33	26	26
ITGAV	-0.003	0.1	-9999	-0.48	22	22
PI3K	-0.017	0.12	-9999	-0.42	21	21
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	-0.003	0.1	-9999	-0.48	22	22
COL4A3	0.013	0.047	-9999	-0.37	7	7
angiogenesis	-0.083	0.22	-9999	-0.65	58	58
Rac1/GTP	-0.013	0.12	-9999	-0.42	11	11
EDIL3	-0.11	0.22	-9999	-0.44	151	151
cell proliferation	0.01	0.093	-9999	-0.35	27	27

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.061	0.16	-10000	0	-0.4	68	68
IKBKB	0.005	0.077	-10000	0	-0.25	10	10
AKT1	-0.017	0.098	0.21	10	-0.23	38	48
IKBKG	0.008	0.078	-10000	0	-0.24	13	13
CALM1	-0.03	0.13	0.21	11	-0.36	44	55
PIK3CA	0.016	0.029	-10000	0	-0.35	3	3
MAP3K1	-0.076	0.19	-10000	0	-0.47	72	72
MAP3K7	0.016	0.021	-10000	0	-0.26	3	3
mol:Ca2+	-0.039	0.13	0.21	11	-0.38	47	58
DOK1	0.002	0.083	-10000	0	-0.41	19	19
AP-1	-0.045	0.1	0.18	1	-0.24	67	68
LYN	0.014	0.031	-10000	0	-0.26	7	7
BLNK	-0.013	0.12	-10000	0	-0.51	31	31
SHC1	0.017	0.023	-10000	0	-0.52	1	1
BCR complex	-0.033	0.13	-10000	0	-0.35	70	70
CD22	-0.056	0.19	-10000	0	-0.49	62	62
CAMK2G	-0.021	0.12	-10000	0	-0.38	31	31
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	-0.45	20	20
GO:0007205	-0.04	0.14	0.21	11	-0.39	47	58
SYK	-0.022	0.14	-10000	0	-0.48	42	42
ELK1	-0.032	0.13	0.21	11	-0.36	46	57
NFATC1	-0.041	0.16	-10000	0	-0.38	61	61
B-cell antigen/BCR complex	-0.033	0.13	-10000	0	-0.35	70	70
PAG1/CSK	0.008	0.074	-10000	0	-0.37	16	16
NFKBIB	0.014	0.031	0.097	1	-0.11	3	4
HRAS	-0.028	0.13	-10000	0	-0.38	34	34
NFKBIA	0.015	0.03	0.097	1	-0.11	2	3
NF-kappa-B/RelA/I kappa B beta	0.02	0.027	0.099	1	-0.16	1	2
RasGAP/Csk	-0.026	0.15	-10000	0	-0.31	78	78
mol:GDP	-0.038	0.13	0.21	11	-0.36	50	61
PTEN	-0.002	0.1	-10000	0	-0.52	19	19
CD79B	-0.042	0.15	-10000	0	-0.36	83	83
NF-kappa-B/RelA/I kappa B alpha	0.02	0.027	0.099	1	-0.16	1	2
GRB2	0.016	0.024	-10000	0	-0.26	4	4
PI3K/BCAP/CD19	-0.063	0.18	-10000	0	-0.5	55	55
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
mol:IP3	-0.04	0.14	0.21	11	-0.39	46	57
CSK	0.015	0.031	-10000	0	-0.32	4	4
FOS	-0.078	0.15	0.21	8	-0.4	63	71
CHUK	0.001	0.094	-10000	0	-0.31	22	22
IBTK	0.016	0.033	-10000	0	-0.52	2	2
CARD11/BCL10/MALT1/TAK1	-0.022	0.12	-10000	0	-0.41	28	28
PTPN6	-0.047	0.18	-10000	0	-0.52	47	47
RELA	0.018	0	-10000	0	-10000	0	0
BCL2A1	0.013	0.03	-10000	0	-0.094	11	11
VAV2	-0.066	0.19	-10000	0	-0.51	60	60
ubiquitin-dependent protein catabolic process	0.019	0.03	0.1	1	-0.1	3	4
BTK	-0.036	0.2	-10000	0	-1.1	18	18
CD19	-0.074	0.2	-10000	0	-0.45	85	85
MAP4K1	0.011	0.041	-10000	0	-0.26	12	12
CD72	-0.031	0.14	-10000	0	-0.38	65	65
PAG1	-0.005	0.097	-10000	0	-0.38	30	30
MAPK14	-0.057	0.17	-10000	0	-0.41	64	64
SH3BP5	-0.005	0.1	-10000	0	-0.44	26	26
PIK3AP1	-0.045	0.16	0.23	11	-0.43	51	62
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.055	0.19	-10000	0	-0.46	63	63
RAF1	-0.019	0.12	-10000	0	-0.38	27	27
RasGAP/p62DOK/SHIP	-0.036	0.15	-10000	0	-0.32	80	80
CD79A	-0.01	0.085	-10000	0	-0.26	53	53
re-entry into mitotic cell cycle	-0.045	0.1	0.18	1	-0.24	67	68
RASA1	0.004	0.079	-10000	0	-0.42	16	16
MAPK3	-0.003	0.1	-10000	0	-0.33	23	23
MAPK1	-0.003	0.1	-10000	0	-0.33	24	24
CD72/SHP1	-0.055	0.19	-10000	0	-0.51	60	60
NFKB1	0.017	0.023	-10000	0	-0.52	1	1
MAPK8	-0.059	0.17	-10000	0	-0.41	67	67
actin cytoskeleton organization	-0.049	0.17	-10000	0	-0.44	58	58
NF-kappa-B/RelA	0.043	0.054	0.19	1	-0.23	3	4
Calcineurin	-0.023	0.12	-10000	0	-0.39	29	29
PI3K	-0.087	0.14	-10000	0	-0.4	67	67
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.043	0.15	0.24	11	-0.43	45	56
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	0.2	1	-0.36	61	62
mol:DAG	-0.04	0.14	0.21	11	-0.39	46	57
PLCG2	-0.017	0.11	-10000	0	-0.32	55	55
MAP2K1	-0.011	0.11	-10000	0	-0.35	26	26
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	62	75
ETS1	-0.018	0.12	-10000	0	-0.4	24	24
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	0.054	-10000	0	-0.38	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	-0.51	57	57
CARD11	-0.038	0.14	0.21	11	-0.38	53	64
FCGR2B	-0.032	0.15	-10000	0	-0.5	51	51
PPP3CA	0.006	0.073	-10000	0	-0.44	13	13
BCL10	0.017	0.012	-10000	0	-0.26	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	-0.22	37	46
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

×

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	-0.038	0.12	0.21	1	-0.34	49	50
PTP1B/AKT1	-0.042	0.12	0.29	2	-0.33	42	44
FYN	0.009	0.063	-10000	0	-0.4	11	11
p210 bcr-abl/PTP1B	-0.054	0.12	0.32	2	-0.32	61	63
EGFR	-0.083	0.18	-10000	0	-0.36	136	136
EGF/EGFR	-0.14	0.2	-10000	0	-0.36	192	192
CSF1	0.014	0.037	-10000	0	-0.3	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	-0.064	0.15	0.28	2	-0.35	71	73
Insulin Receptor/Insulin	-0.019	0.099	-10000	0	-0.36	19	19
HCK	-0.005	0.11	-10000	0	-0.47	25	25
CRK	0.016	0.033	-10000	0	-0.52	2	2
TYK2	-0.044	0.12	0.3	2	-0.32	53	55
EGF	-0.15	0.23	-10000	0	-0.43	193	193
YES1	0.007	0.07	-10000	0	-0.43	12	12
CAV1	-0.072	0.14	0.29	2	-0.36	63	65
TXN	0.013	0.017	-10000	0	-0.26	2	2
PTP1B/IRS1/GRB2	-0.066	0.15	-10000	0	-0.36	80	80
cell migration	0.054	0.12	0.32	61	-0.32	2	63
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	0.021	-10000	0	-0.26	3	3
CSF1R	0.017	0.017	-10000	0	-0.26	2	2
Prolactin Receptor/Prolactin	-0.002	0.12	-10000	0	-0.36	47	47
FGR	0.017	0.017	-10000	0	-0.26	2	2
PTP1B/p130 Cas	-0.043	0.12	0.28	2	-0.32	53	55
Crk/p130 Cas	-0.034	0.12	-10000	0	-0.35	34	34
DOK1	-0.038	0.13	0.3	2	-0.38	40	42
JAK2	-0.036	0.12	-10000	0	-0.33	50	50
Jak2/Leptin Receptor/Leptin	-0.069	0.13	-10000	0	-0.36	52	52
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
PTPN1	-0.055	0.12	0.32	2	-0.32	61	63
LYN	0.014	0.031	-10000	0	-0.26	7	7
CDH2	-0.029	0.13	-10000	0	-0.35	67	67
SRC	-0.004	0.07	-10000	0	-0.68	3	3
ITGB3	0.001	0.076	-10000	0	-0.32	25	25
CAT1/PTP1B	-0.084	0.17	0.25	2	-0.44	63	65
CAPN1	0.003	0.078	-10000	0	-0.44	15	15
CSK	0.015	0.031	-10000	0	-0.32	4	4
PI3K	-0.035	0.1	-10000	0	-0.34	30	30
mol:H2O2	-0.003	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.062	0.12	-10000	0	-0.38	40	40
negative regulation of transcription	-0.036	0.11	-10000	0	-0.32	50	50
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	-0.018	0.1	-10000	0	-0.29	61	61
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	0.091	-10000	0	-0.34	33	33
BCAR1	0.017	0.012	-10000	0	-0.26	1	1
p210 bcr-abl/Grb2	0.016	0.024	-10000	0	-0.26	4	4
mol:NADPH	-0.003	0.004	-10000	0	-10000	0	0
TRPV6	-0.059	0.16	-10000	0	-0.43	55	55
PRL	0.018	0.033	-10000	0	-0.32	4	4
SOCS3	-0.005	0.17	-10000	0	-1.3	8	8
SPRY2	-0.034	0.15	-10000	0	-0.43	58	58
Insulin Receptor/Insulin/IRS1	-0.008	0.12	-10000	0	-0.32	62	62
CSF1/CSF1R	-0.036	0.12	-10000	0	-0.3	54	54
Ras protein signal transduction	0.029	0.038	-10000	0	-0.2	2	2
IRS1	-0.048	0.17	-10000	0	-0.49	68	68
INS	0.017	0.024	-10000	0	-0.53	1	1
LEP	-0.052	0.16	-10000	0	-0.36	99	99
STAT5B	-0.042	0.11	0.25	2	-0.28	62	64
STAT5A	-0.043	0.11	0.25	2	-0.28	63	65
GRB2	0.016	0.024	-10000	0	-0.26	4	4
PDGFB-D/PDGFRB	-0.047	0.13	0.28	2	-0.35	53	55
CSN2	0.019	0.1	-10000	0	-1.4	2	2
PIK3CA	0.016	0.029	-10000	0	-0.35	3	3
LAT	-0.025	0.12	-10000	0	-0.56	19	19
YBX1	0.007	0.073	-10000	0	-0.33	16	16
LCK	-0.073	0.18	-10000	0	-0.4	115	115
SHC1	0.017	0.023	-10000	0	-0.52	1	1
NOX4	-0.057	0.18	-10000	0	-0.49	76	76

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.004	0.13	-10000	0	-0.5	11	11
UGCG	-0.11	0.27	-10000	0	-0.77	74	74
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.07	0.19	-10000	0	-0.39	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	-0.96	8	8
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.14	0.2	-10000	0	-0.46	107	107
FRAP1	-0.12	0.27	-10000	0	-0.54	107	107
FOXO3	-0.064	0.2	-10000	0	-0.42	77	77
AKT1	-0.073	0.21	-10000	0	-0.44	83	83
GAB2	0.008	0.047	-10000	0	-0.26	16	16
SMPD1	-0.004	0.079	-10000	0	-0.8	4	4
SGMS1	-0.01	0.099	-10000	0	-0.74	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	-0.29	25	25
CALM1	0.018	0	-10000	0	-10000	0	0
cell proliferation	-0.088	0.21	-10000	0	-0.47	94	94
EIF3A	0.017	0.012	-10000	0	-0.26	1	1
PI3K	0.006	0.083	-10000	0	-0.36	22	22
RPS6KB1	-0.035	0.1	-10000	0	-0.37	1	1
mol:sphingomyelin	-0.014	0.12	-10000	0	-0.96	8	8
natural killer cell activation	-0.002	0.004	-10000	0	-0.015	9	9
JAK3	0.018	0.004	-10000	0	-10000	0	0
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
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	-0.82	50	50
MYB	-0.23	0.5	-10000	0	-1.2	107	107
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.043	0.16	-10000	0	-0.42	41	41
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.015	0.099	-10000	0	-0.41	3	3
mol:PI-3-4-5-P3	-0.042	0.16	-10000	0	-0.41	41	41
Rac1/GDP	0.011	0.064	-10000	0	-0.28	21	21
T cell proliferation	-0.038	0.15	-10000	0	-0.38	41	41
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	120	120
PRKCZ	-0.041	0.15	-10000	0	-0.4	41	41
NF kappa B1 p50/RelA	-0.085	0.23	-10000	0	-0.46	103	103
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	-0.033	0.14	-10000	0	-0.41	61	61
IL2RB	-0.016	0.12	-10000	0	-0.43	40	40
TERT	0.013	0.042	-10000	0	-0.33	7	7
E2F1	-0.077	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	120	-10000	0	120
PTPN11	0.015	0.024	-10000	0	-0.52	1	1
IL2RG	-0.002	0.079	-10000	0	-0.29	35	35
actin cytoskeleton organization	-0.038	0.15	-10000	0	-0.38	41	41
GRB2	0.014	0.024	-10000	0	-0.26	4	4
IL2	0.011	0.051	-10000	0	-0.34	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	-0.072	0.18	-10000	0	-0.4	115	115
BCL2	-0.19	0.39	-10000	0	-0.87	119	119

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.035	0.05	0.22	3	-0.53	1	4
AES	0.033	0.037	0.2	3	-10000	0	3
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	-0.025	0.14	-10000	0	-0.43	51	51
TLE1	-0.017	0.16	0.2	2	-0.45	55	57
MACF1	0.016	0.026	-10000	0	-0.39	2	2
CTNNB1	-0.006	0.098	0.28	2	-0.36	13	15
WIF1	-0.025	0.1	-10000	0	-0.26	82	82
beta catenin/RanBP3	0.069	0.19	0.37	124	-0.42	2	126
KREMEN2	-0.19	0.23	-10000	0	-0.41	258	258
DKK1	-0.12	0.19	-10000	0	-0.34	198	198
beta catenin/beta TrCP1	0.005	0.097	0.27	2	-0.37	11	13
FZD1	0.003	0.082	-10000	0	-0.43	17	17
AXIN2	-0.098	0.33	-10000	0	-1.3	31	31
AXIN1	0.017	0.012	-10000	0	-0.26	1	1
RAN	0.018	0.012	-10000	0	-0.26	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	0.27	2	-0.48	24	26
Axin1/APC/GSK3	0.049	0.042	0.25	4	-10000	0	4
Axin1/APC/GSK3/beta catenin/Macf1	0.037	0.067	-10000	0	-0.3	2	2
HNF1A	0.031	0.046	0.2	1	-0.25	4	5
CTBP1	0.033	0.041	0.21	2	-0.26	1	3
MYC	-0.12	0.36	-10000	0	-1.2	48	48
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	0.007	0.068	-10000	0	-0.4	13	13
TCF4	0.01	0.12	0.2	2	-0.49	24	26
TCF3	0.028	0.062	0.21	2	-0.38	6	8
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	0.49	123	-0.48	9	132
LEF1	-0.007	0.13	0.2	3	-0.32	63	66
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	-0.5	34	34
DKK1/LRP6/Kremen 2	-0.17	0.18	-10000	0	-0.34	248	248
LRP6	0.008	0.065	-10000	0	-0.38	13	13
CSNK1A1	0.035	0.048	0.21	4	-0.45	1	5
NLK	0.008	0.045	-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	0.029	0.039	0.26	8	-10000	0	8
APC	0.026	0.062	-10000	0	-0.24	23	23
WNT1/LRP6/FZD1	0.038	0.06	-10000	0	-0.24	10	10
CREBBP	0.032	0.051	0.21	1	-0.52	2	3

×

Visual signal transduction: Rods

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	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	-0.046	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	-0.083	0.12	-9999	-0.27	142	142
mol:Na +	-0.042	0.088	-9999	-0.43	13	13
mol:ADP	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.055	0.15	-9999	-0.34	95	95
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.004	0.11	-9999	-0.44	13	13
CNGB1	0.018	0	-9999	-10000	0	0
RDH5	-0.003	0.073	-9999	-0.26	40	40
SAG	-0.099	0.19	-9999	-0.36	162	162
mol:Ca2+	-0.001	0.11	-9999	-0.39	16	16
Na + (4 Units)	-0.04	0.084	-9999	-0.38	16	16
RGS9	-0.032	0.13	-9999	-0.31	80	80
GNB1/GNGT1	-0.033	0.1	-9999	-0.37	18	18
GNAT1/GDP	-0.039	0.13	-9999	-0.28	98	98
GUCY2D	0.018	0	-9999	-10000	0	0
GNGT1	-0.063	0.14	-9999	-0.28	143	143
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	119	119
mol:11-cis-retinal	-0.003	0.073	-9999	-0.26	40	40
mol:cGMP	0.026	0.088	-9999	-0.3	31	31
GNB1	0.013	0.052	-9999	-0.52	5	5
Rhodopsin	0.012	0.05	-9999	-10000	0	0
SLC24A1	0.011	0.056	-9999	-0.42	8	8
CNGA1	-0.063	0.16	-9999	-0.32	125	125
Metarhodopsin II	0.011	0	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.026	0.076	-9999	-0.29	25	25
RGS9BP	-0.071	0.18	-9999	-0.41	110	110
Metarhodopsin II/Transducin	-0.005	0.064	-9999	-0.25	22	22
GCAP Family/Ca ++	0.015	0.075	-9999	-0.3	25	25
PDE6A/B	-0.067	0.17	-9999	-0.37	116	116
mol:Pi	-0.055	0.15	-9999	-0.33	95	95
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.014	0.084	-9999	-0.29	22	22
PDE6B	-0.1	0.22	-9999	-0.5	123	123
PDE6A	0.011	0.048	-9999	-0.31	11	11
PDE6G	0.016	0.024	-9999	-0.26	4	4
RHO	0.018	0	-9999	-10000	0	0
PDE6	-0.088	0.17	-9999	-0.41	62	62
GUCA1A	0.001	0.092	-9999	-0.48	18	18
GC2/GCAP Family	0.02	0.093	-9999	-0.32	31	31
GUCA1C	0.004	0.081	-9999	-0.44	16	16
GUCA1B	0.014	0.035	-9999	-0.3	6	6

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.002	0.077	-9999	-0.3	26	26
NFATC2	0.012	0.044	-9999	-0.3	5	5
NFATC3	0.015	0.031	-9999	-10000	0	0
CD40LG	-0.099	0.26	-9999	-0.55	87	87
PTGS2	-0.11	0.26	-9999	-0.57	87	87
JUNB	0.011	0.055	-9999	-0.36	10	10
CaM/Ca2+/Calcineurin A alpha-beta B1	0.008	0.019	-9999	-10000	0	0
CaM/Ca2+	0.008	0.019	-9999	-10000	0	0
CALM1	0.016	0.009	-9999	-10000	0	0
JUN	-0.035	0.15	-9999	-0.46	57	57
mol:Ca2+	-0.004	0.012	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.01	0.011	-9999	-0.15	2	2
FOSL1	0.016	0.024	-9999	-0.26	4	4
CREM	0.016	0.017	-9999	-0.26	2	2
Jun/NFAT1-c-4/p21SNFT	-0.025	0.15	-9999	-0.36	49	49
FOS	-0.11	0.2	-9999	-0.37	171	171
IFNG	-0.14	0.3	-9999	-0.6	115	115
AP-1/NFAT1-c-4	-0.1	0.31	-9999	-0.62	95	95
FASLG	-0.13	0.3	-9999	-0.62	109	109
NFAT1-c-4/ICER1	0.007	0.095	-9999	-0.31	14	14
IL2RA	-0.12	0.28	-9999	-0.57	106	106
FKBP12/FK506	0.012	0.011	-9999	-0.17	2	2
CSF2	-0.1	0.26	-9999	-0.55	90	90
JunB/Fra1/NFAT1-c-4	0.015	0.1	-9999	-0.32	18	18
IL4	-0.097	0.25	-9999	-0.55	86	86
IL2	-0.005	0.1	-9999	-1.3	3	3
IL3	0.008	0.021	-9999	-10000	0	0
FKBP1A	0.017	0.017	-9999	-0.26	2	2
BATF3	0	0	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.027	0	-9999	-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	-0.035	0.14	-9999	-0.33	75	75
MAP3K8	-0.037	0.15	-9999	-0.39	69	69
FOS	-0.014	0.092	-9999	-0.29	13	13
PRKCA	0.01	0.034	-9999	-0.26	8	8
PTPN7	0.006	0.05	-9999	-0.28	14	14
HRAS	0.011	0.051	-9999	-0.41	7	7
PRKCB	-0.003	0.007	-9999	-0.013	171	171
NRAS	0.005	0.073	-9999	-0.4	15	15
RAS family/GTP	0.013	0.064	-9999	-0.28	20	20
MAPK3	0.001	0.057	-9999	-0.45	2	2
MAP2K1	-0.005	0.065	-9999	-0.23	11	11
ELK1	0.01	0.038	-9999	-0.39	4	4
BRAF	0.004	0.06	-9999	-0.41	8	8
mol:GTP	-0.001	0.002	-9999	-0.004	170	170
MAPK1	0.001	0.06	-9999	-0.43	3	3
RAF1	0.011	0.029	-9999	-10000	0	0
KRAS	0.007	0.069	-9999	-0.45	11	11

×

Coregulation of Androgen receptor activity

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	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	-0.44	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	-0.066	0.14	-9999	-0.33	103	103
CARM1	0.014	0.039	-9999	-0.36	5	5
PRDX1	0.011	0.055	-9999	-0.45	7	7
PELP1	0.017	0.001	-9999	-10000	0	0
CTNNB1	0.002	0.09	-9999	-0.45	19	19
AKT1	0.01	0.054	-9999	-0.38	9	9
PTK2B	0.017	0.017	-9999	-0.26	2	2
MED1	-0.001	0.068	-9999	-0.26	34	34
MAK	-0.018	0.096	-9999	-0.28	56	56
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.019	0.012	-9999	-0.26	1	1
GSN	-0.001	0.098	-9999	-0.43	24	24
NCOA2	0.009	0.063	-9999	-0.4	11	11
NCOA6	0.019	0.012	-9999	-0.26	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	-0.044	0.092	-9999	-0.84	5	5
XRCC5	0.017	0.001	-9999	-10000	0	0
UBE3A	0.018	0.033	-9999	-0.52	2	2
T-DHT/AR/SNURF	-0.077	0.14	-9999	-0.29	139	139
FHL2	-0.16	0.35	-9999	-0.98	73	73
RANBP9	0.019	0.012	-9999	-0.26	1	1
JMJD1A	-0.002	0.056	-9999	-10000	0	0
CDK6	-0.02	0.11	-9999	-0.3	63	63
TGFB1I1	-0.003	0.1	-9999	-0.49	23	23
T-DHT/AR/CyclinD1	-0.13	0.21	-9999	-0.42	154	154
XRCC6	0.016	0.012	-9999	-0.26	1	1
T-DHT/AR	-0.087	0.17	-9999	-0.33	142	142
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	-0.008	0.11	-9999	-0.51	24	24
CDKN2A	-0.055	0.15	-9999	-0.34	108	108
SRF	-0.001	0.055	-9999	-0.28	4	4
NKX3-1	-0.057	0.11	-9999	-0.24	107	107
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	-0.067	0.14	-9999	-0.34	103	103
AR	-0.11	0.22	-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	0.046	-9999	-0.32	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	-0.06	0.13	-9999	-0.3	106	106
RPS6KA3	0.011	0.057	-9999	-0.34	12	12
T-DHT/AR/ARA70	-0.072	0.15	-9999	-0.34	110	110
LATS2	0.004	0.078	-9999	-0.48	13	13
T-DHT/AR/PRX1	-0.064	0.14	-9999	-0.31	107	107
Cyclin D3/CDK11 p58	0.013	0.008	-9999	-0.17	1	1
VAV3	-0.082	0.2	-9999	-0.48	107	107
KLK2	-0.013	0.076	-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	112	112
TMPRSS2	-0.19	0.38	-9999	-0.96	99	99
CCND1	-0.09	0.2	-9999	-0.44	125	125
PIAS1	0.019	0.012	-9999	-0.26	1	1
mol:T-DHT	-0.019	0.037	-9999	-0.077	132	132
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.016	0.05	-9999	-0.43	6	6
T-DHT/AR/CDK6	-0.086	0.17	-9999	-0.38	118	118
CMTM2	0.016	0.023	-9999	-0.52	1	1
SNURF	0	0	-9999	-10000	0	0
ZMIZ1	-0.003	0.05	-9999	-0.32	6	6
CCND3	0.017	0.012	-9999	-0.26	1	1
TGIF1	0.006	0.073	-9999	-0.52	10	10
FKBP4	0.013	0.055	-9999	-0.44	7	7

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.042	0.16	-10000	0	-0.46	66	66
positive regulation of NF-kappaB transcription factor activity	-0.018	0.12	-10000	0	-0.37	51	51
MAP2K4	-0.013	0.12	-10000	0	-0.38	29	29
IKBKB	0.011	0.047	-10000	0	-0.31	10	10
TNFRSF10B	0.004	0.083	-10000	0	-0.47	15	15
TNFRSF10A	-0.003	0.1	-10000	0	-0.46	23	23
SMPD1	-0.008	0.087	-10000	0	-0.23	57	57
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	-0.41	56	56
TRAIL/TRAILR3	-0.031	0.13	-10000	0	-0.37	53	53
TRAIL/TRAILR1	-0.031	0.14	-10000	0	-0.4	62	62
TRAIL/TRAILR4	-0.018	0.12	-10000	0	-0.37	51	51
TRAIL/TRAILR1/DAP3/GTP	-0.012	0.12	-10000	0	-0.3	63	63
IKK complex	-0.028	0.084	-10000	0	-0.41	17	17
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	-0.28	2	2
MAPK3	-0.018	0.12	-10000	0	-0.37	51	51
MAP3K1	-0.009	0.12	-10000	0	-0.3	58	58
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)	-0.003	0.1	-10000	0	-0.46	23	23
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.003	0.11	-10000	0	-0.26	65	65
CFLAR	0.01	0.064	-10000	0	-0.46	9	9
MAPK1	-0.019	0.12	-10000	0	-0.37	52	52
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.001	0.12	-10000	0	-0.29	63	63
mol:ceramide	-0.008	0.086	-10000	0	-0.23	57	57
FADD	0	0.068	-10000	0	-0.26	34	34
MAPK8	-0.007	0.12	-10000	0	-0.39	24	24
TRAF2	0.014	0.042	-10000	0	-0.46	4	4
TRAILR3 (trimer)	-0.004	0.075	-10000	0	-0.26	40	40
CHUK	0.005	0.081	-10000	0	-0.5	13	13
TRAIL/TRAILR1/FADD	-0.023	0.13	-10000	0	-0.34	63	63
DAP3	0.016	0.026	-10000	0	-0.39	2	2
CASP10	-0.049	0.12	0.26	1	-0.37	53	54
JNK cascade	-0.018	0.12	-10000	0	-0.37	51	51
TRAIL (trimer)	-0.041	0.16	-10000	0	-0.46	66	66
TNFRSF10C	-0.004	0.075	-10000	0	-0.26	40	40
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.01	0.12	-10000	0	-0.29	64	64
TRAIL/TRAILR2/FADD	-0.019	0.13	-10000	0	-0.35	57	57
cell death	-0.008	0.086	-10000	0	-0.23	57	57
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0	0.11	-10000	0	-0.27	58	58
TRAILR2 (trimer)	0.004	0.082	-10000	0	-0.47	15	15
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	57	57

×

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	0.071	-9999	-0.29	28	28
Caspase 8 (4 units)	-0.033	0.13	-9999	-0.42	29	29
NEF	-0.015	0.042	-9999	-0.18	10	10
NFKBIA	-0.004	0.061	-9999	-0.52	4	4
BIRC3	-0.065	0.21	-9999	-0.55	74	74
CYCS	-0.039	0.14	-9999	-0.41	35	35
RIPK1	0.017	0.023	-9999	-0.52	1	1
CD247	-0.13	0.24	-9999	-0.47	151	151
MAP2K7	-0.022	0.13	-9999	-0.42	24	24
protein ubiquitination	0.017	0.096	-9999	-0.32	17	17
CRADD	0.009	0.067	-9999	-0.49	9	9
DAXX	0.017	0.012	-9999	-0.26	1	1
FAS	-0.023	0.13	-9999	-0.42	50	50
BID	-0.047	0.14	-9999	-0.42	38	38
NF-kappa-B/RelA/I kappa B alpha	-0.015	0.12	-9999	-0.27	76	76
TRADD	0.016	0.026	-9999	-0.39	2	2
MAP3K5	-0.021	0.13	-9999	-0.42	46	46
CFLAR	0.01	0.064	-9999	-0.46	9	9
FADD	0	0.068	-9999	-0.26	34	34
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.015	0.12	-9999	-0.27	76	76
MAPK8	-0.015	0.12	-9999	-0.44	19	19
APAF1	0.012	0.051	-9999	-0.41	7	7
TRAF1	0.013	0.041	-9999	-0.29	9	9
TRAF2	0.014	0.042	-9999	-0.46	4	4
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.051	0.14	-9999	-0.34	67	67
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.009	0.11	-9999	-0.33	23	23
CHUK	0.016	0.1	-9999	-0.34	17	17
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.001	0.11	-9999	-0.28	54	54
TCRz/NEF	-0.11	0.21	-9999	-0.44	132	132
TNF	-0.004	0.094	-9999	-0.36	31	31
FASLG	-0.12	0.26	-9999	-0.51	132	132
NFKB1	-0.002	0.046	-9999	-0.52	1	1
TNFR1A/BAG4/TNF-alpha	0.012	0.074	-9999	-0.31	18	18
CASP6	-0.019	0.13	-9999	-0.55	17	17
CASP7	-0.072	0.22	-9999	-0.54	79	79
RELA	-0.001	0.04	-9999	-10000	0	0
CASP2	0.018	0	-9999	-10000	0	0
CASP3	-0.065	0.22	-9999	-0.54	77	77
TNFRSF1A	0.016	0.033	-9999	-0.52	2	2
TNFR1A/BAG4	0.014	0.055	-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	-0.35	17	17
APAF-1/Caspase 9	-0.097	0.15	-9999	-0.4	86	86
BCL2	-0.066	0.15	-9999	-0.42	40	40

×

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

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.026	0.14	-10000	0	-0.46	48	48
ANTXR2	0.003	0.087	-10000	0	-0.5	15	15
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.007	0.021	-10000	0	-0.073	46	46
monocyte activation	-0.021	0.12	-10000	0	-0.41	40	40
MAP2K2	0.007	0.06	-10000	0	-0.77	3	3
MAP2K1	0.005	0.021	-10000	0	-0.11	1	1
MAP2K7	0.005	0.024	-10000	0	-0.27	1	1
MAP2K6	-0.01	0.064	-10000	0	-0.21	37	37
CYAA	-0.015	0.091	-10000	0	-0.29	46	46
MAP2K4	-0.006	0.056	-10000	0	-0.21	30	30
IL1B	-0.03	0.095	-10000	0	-0.28	54	54
Channel	-0.01	0.099	-10000	0	-0.31	46	46
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	0.073	46	-10000	0	46
MAPK3	0.004	0.025	-10000	0	-0.19	2	2
MAPK1	0.004	0.027	-10000	0	-0.27	2	2
PGR	-0.14	0.12	-10000	0	-0.21	367	367
PA/Cellular Receptors	-0.012	0.11	-10000	0	-0.34	46	46
apoptosis	-0.007	0.021	-10000	0	-0.073	46	46
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.008	0.094	-10000	0	-0.3	46	46
macrophage activation	0.011	0.028	-10000	0	-0.25	3	3
TNF	-0.004	0.094	-10000	0	-0.36	31	31
VCAM1	-0.021	0.12	-10000	0	-0.42	40	40
platelet activation	0.007	0.027	-10000	0	-10000	0	0
MAPKKK cascade	-0.001	0.034	0.12	18	-10000	0	18
IL18	-0.032	0.11	-10000	0	-0.29	67	67
negative regulation of macrophage activation	-0.007	0.021	-10000	0	-0.073	46	46
LEF	-0.007	0.021	-10000	0	-0.073	46	46
CASP1	-0.006	0.042	-10000	0	-0.15	25	25
mol:cAMP	0.007	0.027	-10000	0	-10000	0	0
necrosis	-0.007	0.021	-10000	0	-0.073	46	46
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.008	0.094	-10000	0	-0.3	46	46
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.044	0.14	-10000	0	-0.36	67	67
fibroblast growth factor receptor signaling pathway	-0.044	0.14	-10000	0	-0.36	67	67
LAMA1	0.015	0.027	-10000	0	-0.26	5	5
PRNP	0.007	0.07	-10000	0	-0.43	12	12
GPC1/SLIT2	-0.024	0.14	-10000	0	-0.39	59	59
SMAD2	0.011	0.085	-10000	0	-0.28	37	37
GPC1/PrPc/Cu2+	0.003	0.082	-10000	0	-0.33	29	29
GPC1/Laminin alpha1	0.007	0.082	-10000	0	-0.37	22	22
TDGF1	0.017	0.012	-10000	0	-0.26	1	1
CRIPTO/GPC1	0.009	0.08	-10000	0	-0.37	22	22
APP/GPC1	-0.024	0.13	-10000	0	-0.38	56	56
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.01	0.081	-10000	0	-0.31	30	30
FLT1	0.005	0.077	-10000	0	-0.45	14	14
GPC1/TGFB/TGFBR1/TGFBR2	0.008	0.094	-10000	0	-0.32	36	36
SERPINC1	0.007	0.055	-10000	0	-0.27	19	19
FYN	0.011	0.078	-10000	0	-0.31	28	28
FGR	0.015	0.068	-10000	0	-0.3	22	22
positive regulation of MAPKKK cascade	-0.011	0.12	-10000	0	-0.36	41	41
SLIT2	-0.028	0.15	-10000	0	-0.48	49	49
GPC1/NRG	0.003	0.087	-10000	0	-0.38	22	22
NRG1	0.009	0.049	-10000	0	-0.26	17	17
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.003	0.096	-10000	0	-0.32	36	36
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	-0.044	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	0.083	-10000	0	-0.42	18	18
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.057	0.14	-10000	0	-0.3	126	126
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	0.076	-10000	0	-0.29	31	31
BLK	-0.004	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	121	121
FGFR1	-0.011	0.1	-10000	0	-0.35	42	42
VEGFR1 homodimer	0.005	0.077	-10000	0	-0.44	14	14
TGFBR2	0.012	0.055	-10000	0	-0.45	7	7
cell death	-0.024	0.13	-10000	0	-0.38	56	56
ATIII/GPC1	0.002	0.088	-10000	0	-0.38	23	23
PLA2G2A/GPC1	-0.043	0.12	-10000	0	-0.39	41	41
LCK	-0.038	0.13	-10000	0	-0.32	81	81
neuron differentiation	0.003	0.087	-10000	0	-0.38	22	22
PrPc/Cu2+	0.006	0.05	-10000	0	-0.31	12	12
APP	-0.028	0.14	-10000	0	-0.42	55	55
TGFBR2 (dimer)	0.012	0.055	-10000	0	-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	41	41
IRAK/TOLLIP	0.029	0.02	-9999	-0.24	1	1
IKBKB	0.011	0.047	-9999	-0.31	10	10
IKBKG	0.018	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.026	0.12	-9999	-0.36	47	47
IL1A	0.006	0.064	-9999	-0.32	18	18
IL1B	-0.067	0.18	-9999	-0.43	86	86
IRAK/TRAF6/p62/Atypical PKCs	0.031	0.054	-9999	-0.23	19	19
IL1R2	-0.046	0.15	-9999	-0.36	89	89
IL1R1	-0.046	0.16	-9999	-0.41	80	80
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.018	0.12	-9999	-0.38	25	25
TOLLIP	0.017	0.012	-9999	-0.26	1	1
TICAM2	0	0	-9999	-10000	0	0
MAP3K3	0.017	0.012	-9999	-0.26	1	1
TAK1/TAB1/TAB2	0.033	0.034	-9999	-0.34	4	4
IKK complex/ELKS	0.051	0.075	-9999	-0.36	7	7
JUN	0.014	0.093	-9999	-0.44	4	4
MAP3K7	0.016	0.021	-9999	-0.26	3	3
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.059	0.18	-9999	-0.35	119	119
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.003	0.1	-9999	-0.28	57	57
PIK3R1	-0.009	0.11	-9999	-0.42	32	32
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	119	119
NFKB1	0.017	0.023	-9999	-0.52	1	1
MAPK8	0.032	0.063	-9999	-0.37	2	2
IRAK1	0.019	0.019	-9999	-10000	0	0
IL1RN/IL1R1	-0.061	0.17	-9999	-0.41	87	87
IRAK4	0.014	0.044	-9999	-0.42	5	5
PRKCI	0.001	0.088	-9999	-0.44	19	19
TRAF6	0.017	0.023	-9999	-0.52	1	1
PI3K	0.006	0.082	-9999	-0.37	21	21
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.032	0.13	-9999	-0.36	48	48
CHUK	0.005	0.081	-9999	-0.5	13	13
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.069	0.18	-9999	-0.36	119	119
IL1 beta/IL1R2	-0.083	0.18	-9999	-0.37	127	127
IRAK/TRAF6/TAK1/TAB1/TAB2	0.048	0.034	-9999	-0.33	1	1
NF kappa B1 p50/RelA	-0.082	0.14	-9999	-0.44	55	55
IRAK3	-0.018	0.1	-9999	-0.28	64	64
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.056	0.17	-9999	-0.34	109	109
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.004	0.089	-9999	-0.38	4	4
IL1 alpha/IL1R1/IL1RAP	-0.014	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	0.022	-9999	-0.25	1	1
IL1RAP	0.011	0.044	-9999	-0.28	11	11
UBE2N	0.017	0.017	-9999	-0.26	2	2
IRAK/TRAF6	-0.07	0.12	-9999	-0.39	50	50
CASP1	-0.051	0.17	-9999	-0.42	83	83
IL1RN/IL1R2	-0.061	0.16	-9999	-0.39	83	83
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.057	0.17	-9999	-0.35	110	110
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	-0.35	3	3
IL1RN	-0.043	0.16	-9999	-0.41	76	76
TRAF6/TAK1/TAB1/TAB2	0.04	0.031	-9999	-0.26	5	5
MAP2K6	0.028	0.063	-9999	-0.4	2	2

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.004	0.089	0.33	33	-10000	0	33
PI3K Class IB/PDE3B	-0.004	0.089	-10000	0	-0.33	33	33
PDE3B	-0.004	0.089	-10000	0	-0.33	33	33

×

Signaling mediated by p38-gamma and p38-delta

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	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	0.091	-9999	-0.28	45	45
CCND1	-0.07	0.17	-9999	-0.42	91	91
p38 gamma/SNTA1	0.003	0.092	-9999	-0.28	34	34
MAP2K3	0.014	0.037	-9999	-0.3	7	7
PKN1	0.013	0.045	-9999	-0.39	6	6
G2/M transition checkpoint	-0.003	0.09	-9999	-0.27	45	45
MAP2K6	-0.005	0.09	-9999	-0.3	42	42
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	0.004	0.071	-9999	-0.33	22	22

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.025	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	0.05	-10000	0	-0.35	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	-0.051	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	-0.48	5	5
NICD/RBPSUH	0.027	0.076	-10000	0	-0.63	6	6
WIF1	-0.025	0.1	-10000	0	-0.26	82	82
NOTCH1	-0.003	0.077	-10000	0	-0.67	6	6
PSENEN	0.017	0.012	-10000	0	-0.26	1	1
KREMEN2	-0.19	0.23	-10000	0	-0.41	258	258
DKK1	-0.12	0.19	-10000	0	-0.34	198	198
beta catenin/beta TrCP1	0.004	0.085	0.24	4	-0.35	17	21
APH1B	0	0.096	-10000	0	-0.51	18	18
APH1A	0.003	0.068	-10000	0	-0.29	25	25
AXIN1	0.006	0.04	0.24	8	-0.25	1	9
CtBP/CBP/TCF1/TLE1/AES	0.036	0.1	0.29	5	-10000	0	5
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	0.016	0.029	-10000	0	-0.25	6	6
CTBP1	0.018	0.018	-10000	0	-0.26	2	2
MYC	-0.086	0.34	-10000	0	-1.4	34	34
NKD1	0.008	0.068	-10000	0	-0.4	13	13
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	-0.051	0.13	-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	-0.26	1	1
PPARD	0.004	0.045	-10000	0	-10000	0	0
Gamma Secretase	0.031	0.071	-10000	0	-0.26	13	13
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	0.18	-10000	0	-0.34	248	248
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	0.075	0.28	4	-0.35	6	10
DKK2	-0.025	0.14	-10000	0	-0.43	51	51
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	0.014	0.039	0.27	7	-10000	0	7
MAPK1	0.016	0.033	-10000	0	-0.52	2	2
WNT1/LRP6/FZD1	0.008	0.08	-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

×

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	0.095	-9999	-0.4	23	23
PTK2	-0.002	0.15	-9999	-0.46	43	43
positive regulation of JNK cascade	-0.028	0.086	-9999	-0.31	44	44
CDC42/GDP	0.021	0.14	-9999	-0.42	42	42
Rac1/GDP	0.023	0.13	-9999	-0.41	42	42
RAP1B	0.013	0.044	-9999	-0.32	8	8
RAP1A	0.011	0.062	-9999	-0.52	7	7
CTNNB1	0.001	0.09	-9999	-0.45	19	19
CDC42/GTP	-0.033	0.11	-9999	-0.38	44	44
nectin-3/I-afadin	-0.017	0.12	-9999	-0.41	42	42
RAPGEF1	0.009	0.15	-9999	-0.47	42	42
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.001	0.17	-9999	-0.54	42	42
PDGFB-D/PDGFRB	0.01	0.066	-9999	-0.52	8	8
TLN1	0.004	0.098	-9999	-0.41	19	19
Rap1/GTP	-0.031	0.094	-9999	-0.33	43	43
IQGAP1	0.018	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.014	0.074	-9999	-0.28	29	29
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.017	0.12	-9999	-0.41	42	42
PVR	0.009	0.055	-9999	-0.32	13	13
Necl-5(dimer)	0.009	0.055	-9999	-0.32	13	13
mol:GDP	0.011	0.16	-9999	-0.51	42	42
MLLT4	-0.006	0.11	-9999	-0.46	26	26
PIK3CA	0.016	0.029	-9999	-0.35	3	3
PI3K	0.001	0.13	-9999	-0.32	60	60
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	0.089	-9999	-0.32	42	42
PVRL1	0.014	0.035	-9999	-0.3	6	6
PVRL3	-0.02	0.13	-9999	-0.4	47	47
PVRL2	0.002	0.089	-9999	-0.52	15	15
PIK3R1	-0.009	0.11	-9999	-0.42	32	32
CDH1	-0.049	0.17	-9999	-0.48	71	71
CLDN1	-0.11	0.21	-9999	-0.4	165	165
JAM-A/CLDN1	-0.066	0.16	-9999	-0.32	128	128
SRC	-0.011	0.18	-9999	-0.61	42	42
ITGB3	0.002	0.076	-9999	-0.32	25	25
nectin-1(dimer)/I-afadin/I-afadin	0.007	0.082	-9999	-0.38	21	21
FARP2	0.005	0.16	-9999	-0.51	44	44
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	-0.003	0.11	-9999	-0.34	44	44
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	44	44
alphaV/beta3 Integrin/Talin	0.006	0.13	-9999	-0.47	21	21
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	-0.003	0.1	-9999	-0.42	20	20
VAV2	0.006	0.16	-9999	-0.52	42	42
RAP1/GDP	0.018	0.13	-9999	-0.38	43	43
ITGAV	-0.003	0.1	-9999	-0.48	22	22
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.01	0.12	-9999	-0.35	54	54
nectin-3(dimer)/I-afadin/I-afadin	-0.017	0.12	-9999	-0.41	42	42
Rac1/GTP	-0.033	0.11	-9999	-0.39	42	42
PTPRM	-0.01	0.11	-9999	-0.3	47	47
E-cadherin/beta catenin/alpha catenin	-0.012	0.13	-9999	-0.46	11	11
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.018	0	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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	-0.037	0.17	-9999	-0.45	74	74
KLHL20	-0.015	0.1	-9999	-0.24	28	28
CYFIP2	-0.042	0.16	-9999	-0.46	65	65
Rac1/GDP	0.006	0.11	-9999	-0.31	16	16
ENAH	-0.036	0.18	-9999	-0.45	76	76
AP1M1	0.017	0.023	-9999	-0.52	1	1
RAP1B	0.012	0.044	-9999	-0.32	8	8
RAP1A	0.011	0.062	-9999	-0.52	7	7
CTNNB1	0.001	0.09	-9999	-0.45	19	19
CDC42/GTP	-0.033	0.07	-9999	-0.3	10	10
ABI1/Sra1/Nap1	-0.042	0.054	-9999	-0.17	40	40
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.006	0.12	-9999	-0.28	79	79
RAPGEF1	-0.015	0.15	-9999	-0.38	74	74
CTNND1	0.016	0.029	-9999	-0.35	3	3
regulation of calcium-dependent cell-cell adhesion	-0.039	0.17	-9999	-0.46	74	74
CRK	-0.025	0.16	-9999	-0.41	74	74
E-cadherin/gamma catenin/alpha catenin	-0.011	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	0.074	-9999	-0.28	29	29
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	-0.029	0.055	-9999	-0.23	12	12
MLLT4	-0.006	0.11	-9999	-0.46	26	26
ARF6/GTP/NME1/Tiam1	0.023	0.053	-9999	-0.3	10	10
PI3K	-0.036	0.07	-9999	-0.3	12	12
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	32	32
CDH1	-0.049	0.17	-9999	-0.48	71	71
RhoA/GDP	0.002	0.12	-9999	-0.38	15	15
actin cytoskeleton organization	-0.009	0.075	-9999	-0.18	28	28
CDC42/GDP	0.007	0.11	-9999	-0.31	16	16
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.008	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	74	74
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	-0.38	15	15
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	-0.028	0.095	-9999	-0.2	100	100
NME1	0.012	0.039	-9999	-0.26	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	0.062	-9999	-0.26	10	10
WASF2	-0.021	0.031	-9999	-0.13	4	4
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	-0.036	0.12	-9999	-0.25	100	100
VAV2	-0.023	0.16	-9999	-0.4	74	74
RAP1/GDP	0.004	0.11	-9999	-0.36	9	9
adherens junction assembly	-0.032	0.17	-9999	-0.43	75	75
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.016	0.021	-9999	-0.26	3	3
PIP5K1C	0.014	0.042	-9999	-0.46	4	4
regulation of heterotypic cell-cell adhesion	0.006	0.11	-9999	-0.37	5	5
E-cadherin/beta catenin	-0.045	0.11	-9999	-0.34	66	66
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.033	0.17	-9999	-0.44	75	75
PIK3CA	0.016	0.029	-9999	-0.35	3	3
Rac1/GTP	-0.079	0.12	-9999	-0.38	36	36
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

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	5	-0.37	156	161
AKT1	0.01	0.056	-10000	0	-0.37	9	9
GSC	-0.2	0.49	-10000	0	-1.4	76	76
NKX2-5	-0.018	0.094	-10000	0	-0.26	67	67
muscle cell differentiation	0.065	0.16	0.47	45	-10000	0	45
SMAD2-3/SMAD4/SP1	-0.004	0.18	-10000	0	-0.43	53	53
SMAD4	-0.015	0.1	-10000	0	-0.38	21	21
CBFB	0.015	0.037	-10000	0	-0.39	4	4
SAP18	0.017	0.001	-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	-0.39	21	21
MYC	-0.024	0.14	-10000	0	-0.44	48	48
CDKN2B	-0.044	0.29	-10000	0	-1.4	23	23
AP1	-0.068	0.22	-10000	0	-0.59	63	63
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	0.006	0.12	-10000	0	-0.35	30	30
SP3	0.014	0.02	-10000	0	-10000	0	0
CREB1	0.017	0.023	-10000	0	-0.52	1	1
FOXH1	0	0.041	-10000	0	-10000	0	0
SMAD3/SMAD4/GR	-0.005	0.13	-10000	0	-0.36	45	45
GATA3	-0.098	0.22	-10000	0	-0.5	124	124
SKI/SIN3/HDAC complex/NCoR1	0.042	0.037	-10000	0	-10000	0	0
MEF2C/TIF2	-0.026	0.17	-10000	0	-0.52	37	37
endothelial cell migration	0.015	0.23	1.3	15	-10000	0	15
MAX	0.018	0.009	-10000	0	-10000	0	0
RBBP7	0.009	0.051	-10000	0	-0.3	13	13
RBBP4	0.016	0.026	-10000	0	-0.39	2	2
RUNX2	0.013	0.05	-10000	0	-0.43	6	6
RUNX3	-0.063	0.18	-10000	0	-0.4	102	102
RUNX1	-0.028	0.14	-10000	0	-0.42	56	56
CTBP1	0.017	0.017	-10000	0	-0.26	2	2
NR3C1	-0.003	0.1	-10000	0	-0.51	21	21
VDR	-0.003	0.1	-10000	0	-0.51	21	21
CDKN1A	-0.027	0.26	-10000	0	-1.2	19	19
KAT2B	0.001	0.006	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.014	0.13	-10000	0	-0.31	58	58
DCP1A	0.017	0.023	-10000	0	-0.52	1	1
SKI	0.016	0.017	-10000	0	-0.26	2	2
SERPINE1	-0.017	0.23	-10000	0	-1.3	15	15
SMAD3/SMAD4/ATF2	0.007	0.1	-10000	0	-0.33	28	28
SMAD3/SMAD4/ATF3	-0.017	0.14	-10000	0	-0.35	55	55
SAP30	0.012	0.053	-10000	0	-0.48	6	6
Cbp/p300/PIAS3	0.047	0.053	-10000	0	-0.28	6	6
JUN	-0.07	0.22	-10000	0	-0.58	63	63
SMAD3/SMAD4/IRF7	0.003	0.13	-10000	0	-0.4	29	29
TFE3	0.018	0.026	-10000	0	-10000	0	0
COL1A2	-0.099	0.36	-10000	0	-1	70	70
mesenchymal cell differentiation	-0.004	0.11	0.36	30	-10000	0	30
DLX1	-0.009	0.082	-10000	0	-0.26	52	52
TCF3	0.012	0.05	-10000	0	-0.35	9	9
FOS	-0.11	0.2	-10000	0	-0.38	171	171
SMAD3/SMAD4/Max	0.008	0.1	-10000	0	-0.33	28	28
Cbp/p300/SNIP1	0.035	0.046	-10000	0	-0.3	9	9
ZBTB17	0.019	0.012	-10000	0	-10000	0	0
LAMC1	0.005	0.14	-10000	0	-0.53	28	28
TGIF2/HDAC complex/SMAD3/SMAD4	0	0.12	-10000	0	-0.35	35	35
IRF7	0.008	0.076	-10000	0	-0.49	11	11
ESR1	-0.15	0.23	-10000	0	-0.45	188	188
HNF4A	0.016	0.033	-10000	0	-0.52	2	2
MEF2C	-0.033	0.17	-10000	0	-0.55	38	38
SMAD2-3/SMAD4	-0.007	0.12	-10000	0	-0.35	37	37
Cbp/p300/Src-1	0.036	0.054	-10000	0	-0.28	12	12
IGHV3OR16-13	-0.017	0.039	-10000	0	-0.52	1	1
TGIF2/HDAC complex	0.007	0.071	-10000	0	-0.42	13	13
CREBBP	0.019	0.034	-10000	0	-0.51	2	2
SKIL	0.005	0.071	-10000	0	-0.34	19	19
HDAC1	0.016	0.023	-10000	0	-0.52	1	1
HDAC2	0.008	0.054	-10000	0	-0.29	15	15
SNIP1	0.014	0.04	-10000	0	-0.52	3	3
GCN5L2	0.018	0.044	-10000	0	-0.46	4	4
SMAD3/SMAD4/TFE3	0.015	0.12	-10000	0	-0.37	31	31
MSG1/HSC70	-0.02	0.098	-10000	0	-0.41	16	16
SMAD2	-0.002	0.05	-10000	0	-0.51	1	1
SMAD3	-0.003	0.1	-10000	0	-0.5	15	15
SMAD3/E2F4-5/DP1/p107/SMAD4	0.008	0.097	-10000	0	-0.32	19	19
SMAD2/SMAD2/SMAD4	-0.006	0.054	-10000	0	-0.3	10	10
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	-0.002	0.099	-10000	0	-0.37	32	32
SMAD2-3/SMAD4/SP1/MIZ-1	0.009	0.17	-10000	0	-0.43	44	44
IFNB1	0.006	0.13	-10000	0	-0.45	25	25
SMAD3/SMAD4/MEF2C	-0.026	0.2	-10000	0	-0.56	44	44
CITED1	-0.029	0.11	-10000	0	-0.26	88	88
SMAD2-3/SMAD4/ARC105	0.01	0.11	-10000	0	-0.33	27	27
RBL1	0.01	0.049	-10000	0	-0.28	14	14
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.002	0.15	-10000	0	-0.47	33	33
RUNX1-3/PEBPB2	-0.043	0.14	-10000	0	-0.34	86	86
SMAD7	-0.041	0.22	-10000	0	-0.64	38	38
MYC/MIZ-1	-0.003	0.1	-10000	0	-0.37	34	34
SMAD3/SMAD4	0.046	0.14	0.29	46	-0.4	15	61
IL10	-0.046	0.18	-10000	0	-0.44	55	55
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	-0.046	0.18	-10000	0	-0.46	45	45
CDK4	0.019	0.03	-10000	0	-0.26	5	5
PIAS4	0.009	0.051	-10000	0	-0.44	6	6
ATF3	-0.021	0.13	-10000	0	-0.41	48	48
SMAD3/SMAD4/SP1	-0.008	0.17	-10000	0	-0.44	52	52
FOXG1	-0.007	0.083	-10000	0	-0.28	44	44
FOXO3	0.015	0.061	-10000	0	-0.4	8	8
FOXO1	0.008	0.079	-10000	0	-0.37	19	19
FOXO4	0.019	0.047	-10000	0	-0.37	5	5
heart looping	-0.033	0.17	-10000	0	-0.54	38	38
CEBPB	0.004	0.073	-10000	0	-0.34	20	20
SMAD3/SMAD4/DLX1	-0.009	0.12	-10000	0	-0.37	26	26
MYOD1	-0.016	0.13	-10000	0	-0.46	37	37
SMAD3/SMAD4/HNF4	0.006	0.11	-10000	0	-0.34	28	28
SMAD3/SMAD4/GATA3	-0.061	0.2	-10000	0	-0.41	99	99
SnoN/SIN3/HDAC complex/NCoR1	0.005	0.071	-10000	0	-0.34	19	19
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.037	0.17	-10000	0	-0.38	71	71
SMAD3/SMAD4/SP1-3	0.001	0.18	-10000	0	-0.49	45	45
MED15	0.018	0	-10000	0	-10000	0	0
SP1	-0.001	0.068	-10000	0	-0.4	3	3
SIN3B	0.017	0.012	-10000	0	-0.26	1	1
SIN3A	0.017	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.019	0.15	-10000	0	-0.38	46	46
ITGB5	-0.03	0.23	-10000	0	-0.65	55	55
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	-0.015	0.13	-10000	0	-0.32	58	58
E2F5	-0.014	0.12	-10000	0	-0.39	41	41
E2F4	0.017	0.017	-10000	0	-0.26	2	2
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.012	0.11	-10000	0	-0.32	18	18
SMAD2-3/SMAD4/FOXO1-3a-4	0.007	0.12	-10000	0	-0.35	40	40
TFDP1	0.011	0.043	-10000	0	-0.26	13	13
SMAD3/SMAD4/AP1	-0.063	0.23	-10000	0	-0.59	63	63
SMAD3/SMAD4/RUNX2	0.004	0.11	-10000	0	-0.36	30	30
TGIF2	0.007	0.071	-10000	0	-0.42	13	13
TGIF1	0.008	0.073	-10000	0	-0.52	10	10
ATF2	0.018	0	-10000	0	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.003	0.069	-9999	-0.29	26	26
Syndecan-3/Src/Cortactin	-0.046	0.16	-9999	-0.52	34	34
Syndecan-3/Neurocan	-0.007	0.13	-9999	-0.57	24	24
POMC	0.001	0.072	-9999	-0.28	30	30
EGFR	-0.077	0.17	-9999	-0.35	136	136
Syndecan-3/EGFR	-0.048	0.16	-9999	-0.39	66	66
AGRP	0.016	0.029	-9999	-0.35	3	3
NCSTN	0.017	0.023	-9999	-0.52	1	1
PSENEN	0.017	0.012	-9999	-0.26	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0	0.096	-9999	-0.51	18	18
APH1A	0.003	0.068	-9999	-0.29	25	25
NCAN	0.007	0.054	-9999	-0.26	21	21
long-term memory	-0.003	0.13	-9999	-0.55	25	25
Syndecan-3/IL8	-0.046	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	0.009	0.063	-9999	-0.4	11	11
limb bud formation	-0.032	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	-0.38	157	157
FGFR/FGF/Syndecan-3	-0.032	0.12	-9999	-0.6	24	24
neuron projection morphogenesis	-0.045	0.16	-9999	-0.5	36	36
Syndecan-3/AgRP	-0.003	0.13	-9999	-0.56	25	25
Syndecan-3/AgRP/MC4R	0.005	0.13	-9999	-0.56	24	24
Fyn/Cortactin	0.01	0.067	-9999	-0.38	9	9
SDC3	-0.032	0.13	-9999	-0.61	24	24
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.045	0.15	-9999	-0.41	58	58
IL8	-0.073	0.17	-9999	-0.34	135	135
Syndecan-3/Fyn/Cortactin	-0.003	0.13	-9999	-0.56	25	25
Syndecan-3/CASK	-0.031	0.12	-9999	-0.58	24	24
alpha-MSH/MC4R	0.012	0.057	-9999	-0.37	5	5
Gamma Secretase	0.032	0.07	-9999	-0.36	1	1

×

PDGFR-alpha 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	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	-0.005	0.097	-9999	-0.37	33	33
AP1	-0.18	0.34	-9999	-0.91	83	83
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	-0.018	0.12	-9999	-0.4	48	48
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	-0.35	3	3
CAV1	0	0.081	-9999	-0.32	28	28
SHC/Grb2/SOS1	0.02	0.077	-9999	-0.26	34	34
PDGF/PDGFRA/Shf	-0.009	0.1	-9999	-0.37	34	34
FOS	-0.17	0.34	-9999	-0.89	83	83
JUN	-0.051	0.11	-9999	-0.41	43	43
oligodendrocyte development	-0.018	0.12	-9999	-0.39	48	48
GRB2	0.016	0.024	-9999	-0.26	4	4
PIK3R1	-0.009	0.11	-9999	-0.42	32	32
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	0.009	0.05	-9999	-0.28	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	-0.015	0.12	-9999	-0.4	36	36
ITGAV	-0.003	0.1	-9999	-0.48	22	22
ELK1	-0.018	0.1	-9999	-0.36	36	36
PIK3CA	0.016	0.029	-9999	-0.35	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	34	34

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.1	0.22	-10000	0	-0.56	71	71
RAD9A	0.018	0	-10000	0	-10000	0	0
AP1	-0.1	0.18	-10000	0	-0.42	107	107
IFNAR2	0.013	0.037	-10000	0	-0.31	6	6
AKT1	-0.053	0.12	-10000	0	-0.26	70	70
ER alpha/Oestrogen	-0.12	0.17	-10000	0	-0.33	202	202
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	-0.35	3	3
SMG6	0.017	0.023	-10000	0	-0.52	1	1
SP3/HDAC2	0.018	0.041	-10000	0	-0.25	6	6
TERT/c-Abl	-0.089	0.21	-10000	0	-0.54	62	62
SAP18	0.017	0.001	-10000	0	-10000	0	0
MRN complex	0.029	0.047	-10000	0	-0.3	10	10
WT1	-0.1	0.19	-10000	0	-0.35	170	170
WRN	0.012	0.05	-10000	0	-0.35	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	-0.53	42	42
Mad/Max	0.021	0.024	-10000	0	-10000	0	0
TERT	-0.1	0.23	-10000	0	-0.6	62	62
CCND1	-0.2	0.43	-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	-0.073	0.19	-10000	0	-0.44	84	84
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	-0.26	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	-0.077	0.16	-10000	0	-0.37	103	103
PARP2	0.017	0.012	-10000	0	-0.26	1	1
BLM	-0.021	0.13	-10000	0	-0.41	48	48
Telomerase	0.025	0.06	-10000	0	-0.36	3	3
IRF1	-0.018	0.12	-10000	0	-0.38	41	41
ESR1	-0.16	0.24	-10000	0	-0.45	202	202
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	-0.46	1	1
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.043	0.052	-10000	0	-0.47	1	1
HDAC1	0.016	0.023	-10000	0	-0.52	1	1
HDAC2	0.008	0.056	-10000	0	-0.3	15	15
ATM	0.001	0.017	0.21	3	-10000	0	3
SMAD3	0.015	0.06	-10000	0	-0.36	11	11
ABL1	0.018	0	-10000	0	-10000	0	0
MXD1	0.013	0.032	-10000	0	-0.26	7	7
MRE11A	0.018	0	-10000	0	-10000	0	0
HUS1	0.016	0.021	-10000	0	-0.26	3	3
RPS6KB1	0.008	0.05	-10000	0	-0.26	18	18
TERT/NF kappa B1/14-3-3	-0.091	0.22	-10000	0	-0.56	70	70
NR2F2	-0.05	0.17	-10000	0	-0.45	78	78
MAPK3	0.019	0.042	-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	-0.078	0.17	-10000	0	-0.35	136	136
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.15	0.2	-10000	0	-0.42	172	172
MYC	-0.027	0.14	-10000	0	-0.43	51	51
IL2	0.01	0.052	-10000	0	-0.34	10	10
KU	0.026	0.008	-10000	0	-10000	0	0
RAD50	0.01	0.066	-10000	0	-0.52	8	8
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	-0.56	52	52
SP1/HDAC2	0.019	0.048	-10000	0	-0.34	5	5
PINX1	0.016	0.021	-10000	0	-0.26	3	3
Telomerase/EST1A	-0.099	0.17	-10000	0	-0.53	42	42
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	-0.093	0.18	-10000	0	-0.33	161	161
Telomerase/PinX1	-0.099	0.17	-10000	0	-0.53	42	42
Telomerase/AKT1/mTOR/p70S6K	-0.008	0.092	-10000	0	-0.47	5	5
SIN3B	0.017	0.012	-10000	0	-0.26	1	1
YWHAE	0.016	0.029	-10000	0	-0.35	3	3
Telomerase/EST1B	-0.1	0.18	-10000	0	-0.53	45	45
response to DNA damage stimulus	0.004	0.005	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.044	0.049	-10000	0	-0.26	12	12
TRF2/WRN	0.02	0.043	-10000	0	-0.35	6	6
Telomerase/hnRNP C1/C2	-0.099	0.17	-10000	0	-0.53	42	42
E2F1	0.005	0.071	-10000	0	-0.38	16	16
ZNFX1	0.007	0.071	-10000	0	-0.42	13	13
PIF1	0.015	0.027	-10000	0	-0.26	5	5
NCL	0.018	0	-10000	0	-10000	0	0
DKC1	0.016	0.021	-10000	0	-0.26	3	3
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	0.019	0.061	-9999	-0.27	21	21
RGS9BP	-0.071	0.18	-9999	-0.41	110	110
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	-0.31	3	3
GNAT2	-0.004	0.1	-9999	-0.49	23	23
RGS9-1/Gbeta5/R9AP	-0.055	0.15	-9999	-0.34	95	95
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	0.087	-9999	-0.3	39	39
Cone Metarhodopsin II/X-Arrestin	0.013	0.008	-9999	-0.17	1	1
mol:Ca2+	-0.01	0.084	-9999	-0.3	27	27
Cone PDE6	-0.042	0.14	-9999	-0.29	104	104
Cone Metarhodopsin II	0.01	0.019	-9999	-0.29	2	2
Na + (4 Units)	-0.005	0.086	-9999	-0.29	27	27
GNAT2/GDP	-0.048	0.14	-9999	-0.29	111	111
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	-0.42	5	5
GNB3/GNGT2	0.025	0.026	-9999	-0.37	2	2
GNB3	0.017	0.012	-9999	-0.26	1	1
GNAT2/GTP	-0.003	0.076	-9999	-0.35	23	23
CNGA3	-0.028	0.12	-9999	-0.32	72	72
ARR3	0.017	0.012	-9999	-0.26	1	1
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.016	0.09	-9999	-0.33	24	24
mol:Pi	-0.055	0.15	-9999	-0.33	95	95
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	-0.42	5	5
RGS9	-0.032	0.13	-9999	-0.31	80	80
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	0.094	-9999	-0.45	21	21

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.018	0.072	0.24	15	-0.23	29	44
DAPP1	-0.037	0.14	-10000	0	-0.42	42	42
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.049	0.22	-10000	0	-0.54	61	61
mol:DAG	0.001	0.1	0.2	8	-0.23	43	51
HRAS	0.012	0.051	-10000	0	-0.41	7	7
RAP1A	0.011	0.062	-10000	0	-0.52	7	7
ARF5/GDP	-0.016	0.11	-10000	0	-0.28	39	39
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	0.069	0.22	15	-0.25	26	41
ARF1/GTP	-0.006	0.067	0.22	15	-0.24	26	41
RHOA	0.005	0.08	-10000	0	-0.52	12	12
YES1	0.007	0.07	-10000	0	-0.43	12	12
RAP1A/GTP	0.014	0.07	0.22	15	-0.25	26	41
ADAP1	-0.006	0.066	0.21	15	-0.24	26	41
ARAP3	-0.006	0.068	0.22	15	-0.24	26	41
INPPL1	0.012	0.055	-10000	0	-0.45	7	7
PREX1	-0.089	0.2	-10000	0	-0.44	124	124
ARHGEF6	-0.019	0.13	-10000	0	-0.42	45	45
ARHGEF7	0.016	0.021	-10000	0	-0.26	3	3
ARF1	0.017	0.023	-10000	0	-0.52	1	1
NRAS	0.006	0.073	-10000	0	-0.4	15	15
FYN	0.009	0.063	-10000	0	-0.4	11	11
ARF6	0.016	0.033	-10000	0	-0.52	2	2
FGR	0.017	0.017	-10000	0	-0.26	2	2
mol:Ca2+	0.006	0.054	-10000	0	-0.15	1	1
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.006	0.073	-10000	0	-0.44	13	13
ZAP70	0.005	0.061	-10000	0	-0.27	24	24
mol:IP3	0.004	0.073	-10000	0	-0.18	25	25
LYN	0.014	0.031	-10000	0	-0.26	7	7
ARF1/GDP	-0.015	0.1	-10000	0	-0.3	34	34
RhoA/GDP	0.002	0.1	0.23	6	-0.34	26	32
PDK1/Src/Hsp90	0.031	0.039	-10000	0	-0.3	6	6
BLNK	-0.013	0.12	-10000	0	-0.51	31	31
actin cytoskeleton reorganization	-0.007	0.12	0.23	6	-0.41	24	30
SRC	0.015	0.035	-10000	0	-0.43	3	3
PLEKHA2	0.014	0.041	-10000	0	-0.31	7	7
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	0.07	0.24	14	-0.24	21	35
RhoA/GTP	0.015	0.083	0.22	14	-0.27	31	45
Src family/SYK family/BLNK-LAT	-0.03	0.17	-10000	0	-0.46	46	46
BLK	-0.018	0.1	-10000	0	-0.29	61	61
PDPK1	0.016	0.026	-10000	0	-0.39	2	2
CYTH1	-0.006	0.066	0.21	15	-0.24	26	41
HCK	-0.005	0.11	-10000	0	-0.47	25	25
CYTH3	-0.006	0.066	0.21	15	-0.24	26	41
CYTH2	-0.006	0.066	0.21	15	-0.24	26	41
KRAS	0.008	0.069	-10000	0	-0.45	11	11
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.025	0.052	-10000	0	-0.22	5	5
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	-0.3	41	41
SOS1	0.017	0.023	-10000	0	-0.52	1	1
SYK	-0.022	0.14	-10000	0	-0.48	42	42
ARF6/GDP	0.005	0.085	0.24	6	-0.3	20	26
mol:PI-3-4-5-P3	-0.004	0.075	0.25	19	-0.25	26	45
ARAP3/RAP1A/GTP	0.014	0.071	0.22	15	-0.25	26	41
VAV1	-0.015	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	0.021	0.07	-10000	0	-0.25	26	26
PLEKHA1	0.012	0.052	-10000	0	-0.32	12	12
Rac1/GDP	-0.014	0.1	-10000	0	-0.32	28	28
LAT	0.002	0.069	-10000	0	-0.28	29	29
Rac1/GTP	-0.03	0.14	-10000	0	-0.4	42	42
ITK	-0.008	0.1	0.22	14	-0.24	62	76
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.008	0.13	0.22	8	-0.32	47	55
LCK	-0.073	0.18	-10000	0	-0.4	115	115
BTK	0.006	0.092	0.22	14	-0.27	38	52

×

Ceramide signaling 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
SPHK2	0.01	0.072	-10000	0	-0.37	17	17
MAP4K4	-0.002	0.11	-10000	0	-0.36	20	20
BAG4	0.002	0.071	-10000	0	-0.29	28	28
PKC zeta/ceramide	-0.025	0.04	0.13	8	-0.12	1	9
NFKBIA	0.014	0.042	-10000	0	-0.46	4	4
BIRC3	-0.086	0.19	-10000	0	-0.41	129	129
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	-0.35	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	0.094	0.15	6	-0.28	56	62
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	4	-0.18	1	5
EGF	-0.14	0.23	-10000	0	-0.42	193	193
mol:ceramide	-0.027	0.044	0.14	11	-0.12	1	12
MADD	0.018	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.027	0.13	-10000	0	-0.38	54	54
ASAH1	-0.037	0.15	-10000	0	-0.42	65	65
negative regulation of cell cycle	-0.028	0.069	0.15	8	-0.31	20	28
cell proliferation	-0.036	0.097	-10000	0	-0.23	84	84
BID	-0.013	0.12	-10000	0	-0.52	19	19
MAP3K1	-0.042	0.085	0.15	7	-0.24	56	63
EIF2A	-0.013	0.06	-10000	0	-0.25	17	17
TRADD	0.016	0.026	-10000	0	-0.39	2	2
CRADD	0.009	0.067	-10000	0	-0.49	9	9
MAPK3	0.001	0.039	-10000	0	-0.19	1	1
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.001	0.04	-10000	0	-0.19	1	1
Cathepsin D/ceramide	-0.022	0.056	0.14	8	-0.23	12	20
FADD	-0.006	0.11	-10000	0	-0.37	21	21
KSR1	-0.018	0.042	0.15	8	-0.2	1	9
MAPK8	-0.031	0.069	0.14	6	-0.19	54	60
PRKRA	-0.018	0.041	0.14	11	-0.12	2	13
PDGFA	-0.001	0.094	-10000	0	-0.44	22	22
TRAF2	0.014	0.042	-10000	0	-0.46	4	4
IGF1	-0.1	0.21	-10000	0	-0.42	146	146
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.027	0.044	0.14	11	-0.12	1	12
CTSD	0.003	0.074	-10000	0	-0.33	23	23
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	-0.036	0.11	-10000	0	-0.25	84	84
PRKCD	0.014	0.042	-10000	0	-0.46	4	4
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.027	0.13	-10000	0	-0.38	54	54
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	-0.006	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	0.072	-10000	0	-0.37	17	17
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	0.066	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	0.055	-10000	0	-0.37	5	5
EIF2AK2	-0.019	0.062	0.15	8	-0.26	18	26
TNF-alpha/TNFR1A/FAN	0.016	0.074	-10000	0	-0.31	21	21
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.02	0.062	-10000	0	-0.26	7	7
MAP2K2	-0.004	0.043	-10000	0	-0.27	3	3
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	0.21	133	-10000	0	133
NF kappa B1/RelA/I kappa B alpha	0.03	0.055	-10000	0	-0.25	18	18
AIFM1	0.027	0.066	0.16	76	-10000	0	76
BCL2	-0.12	0.22	-10000	0	-0.47	145	145

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.023	0.029	-9999	-0.37	1	1
VLDLR	-0.059	0.17	-9999	-0.4	98	98
CRKL	0.014	0.047	-9999	-0.52	4	4
LRPAP1	0.016	0.026	-9999	-0.39	2	2
FYN	0.009	0.063	-9999	-0.4	11	11
ITGA3	-0.003	0.096	-9999	-0.42	25	25
RELN/VLDLR/Fyn	-0.021	0.12	-9999	-0.32	61	61
MAPK8IP1/MKK7/MAP3K11/JNK1	0.038	0.061	-9999	-0.26	18	18
AKT1	-0.01	0.11	-9999	-0.43	14	14
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	41	41
LRPAP1/LRP8	-0.027	0.11	-9999	-0.37	36	36
RELN/LRP8/DAB1/Fyn	-0.005	0.093	-9999	-0.26	47	47
DAB1/alpha3/beta1 Integrin	-0.066	0.1	-9999	-0.36	24	24
long-term memory	-0.002	0.1	-9999	-0.37	5	5
DAB1/LIS1	-0.027	0.12	-9999	-0.38	14	14
DAB1/CRLK/C3G	-0.058	0.096	-9999	-0.37	15	15
PIK3CA	0.016	0.029	-9999	-0.35	3	3
DAB1/NCK2	-0.028	0.12	-9999	-0.36	15	15
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	-0.26	1	1
CDK5R1	0.014	0.031	-9999	-0.26	7	7
RELN	0.009	0.059	-9999	-0.38	11	11
PIK3R1	-0.009	0.11	-9999	-0.42	32	32
RELN/LRP8/Fyn	-0.019	0.11	-9999	-0.31	47	47
GRIN2A/RELN/LRP8/DAB1/Fyn	0.004	0.095	-9999	-0.25	46	46
MAPK8	0.015	0.04	-9999	-0.52	3	3
RELN/VLDLR/DAB1	-0.013	0.1	-9999	-0.28	57	57
ITGB1	0.015	0.037	-9999	-0.39	4	4
MAP1B	-0.056	0.14	-9999	-0.29	109	109
RELN/LRP8	-0.014	0.1	-9999	-0.31	42	42
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.009	0.11	-9999	-0.26	64	64
PI3K	0.006	0.082	-9999	-0.37	21	21
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.01	0.077	-9999	-0.39	16	16
RAP1A	-0.019	0.12	-9999	-0.36	16	16
PAFAH1B1	0.017	0.023	-9999	-0.52	1	1
MAPK8IP1	0.011	0.048	-9999	-0.31	11	11
CRLK/C3G	0.023	0.034	-9999	-0.37	4	4
GRIN2B	-0.007	0.11	-9999	-0.43	29	29
NCK2	0.015	0.027	-9999	-0.26	5	5
neuron differentiation	0.012	0.077	-9999	-0.3	4	4
neuron adhesion	-0.015	0.12	-9999	-0.44	8	8
LRP8	-0.057	0.16	-9999	-0.34	109	109
GSK3B	-0.003	0.1	-9999	-0.42	13	13
RELN/VLDLR/DAB1/Fyn	-0.007	0.1	-9999	-0.27	61	61
MAP3K11	0.015	0.035	-9999	-0.43	3	3
RELN/VLDLR/DAB1/P13K	-0.015	0.11	-9999	-0.26	72	72
CDK5	0.016	0.026	-9999	-0.39	2	2
MAPT	-0.09	0.2	-9999	-0.48	107	107
neuron migration	-0.011	0.12	-9999	-0.36	22	22
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.012	0.078	-9999	-0.31	4	4
RELN/VLDLR	-0.043	0.13	-9999	-0.28	111	111

×

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	0.047	-9999	-0.26	16	16
ELF1	-0.013	0.12	-9999	-0.37	45	45
CCNA2	-0.024	0.13	-9999	-0.4	53	53
PIK3CA	0.016	0.029	-9999	-0.34	3	3
JAK3	0.018	0	-9999	-10000	0	0
PIK3R1	-0.008	0.11	-9999	-0.42	32	32
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	-0.45	25	25
SHC1	0.018	0.023	-9999	-0.52	1	1
SP1	0.016	0.069	-9999	-0.36	15	15
IL2RA	-0.036	0.21	-9999	-0.68	44	44
IL2RB	-0.016	0.12	-9999	-0.44	40	40
SOS1	0.017	0.023	-9999	-0.52	1	1
IL2RG	-0.002	0.079	-9999	-0.29	35	35
G1/S transition of mitotic cell cycle	-0.024	0.2	-9999	-0.56	47	47
PTPN11	0.018	0.023	-9999	-0.52	1	1
CCND2	0.011	0.14	-9999	-0.77	15	15
LCK	-0.072	0.18	-9999	-0.4	115	115
GRB2	0.016	0.024	-9999	-0.26	4	4
IL2	0.012	0.051	-9999	-0.34	10	10
CDK6	-0.02	0.11	-9999	-0.3	63	63
CCND3	0.021	0.13	-9999	-0.46	13	13

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.048	0.1	-9999	-0.26	86	86
TC10/GTP	-0.021	0.061	-9999	-0.48	1	1
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	-0.37	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	0.035	0.08	-9999	-0.49	4	4
mol:GTP	0	0	-9999	-10000	0	0
GRB10	-0.003	0.098	-9999	-0.43	24	24
SORBS1	-0.032	0.14	-9999	-0.39	64	64
CRK	0.016	0.033	-9999	-0.52	2	2
PTPN1	0.023	0.076	-9999	-0.48	4	4
CAV1	-0.011	0.11	-9999	-0.27	68	68
CBL/APS/CAP/Crk-II/C3G	0.015	0.077	-9999	-0.25	34	34
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	-0.041	0.095	-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	0.006	0.074	-9999	-0.43	14	14
CBL	0.017	0.012	-9999	-0.26	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	32	32
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.082	0.11	-9999	-0.33	51	51
HRAS/GTP	-0.028	0.073	-9999	-0.41	4	4
Insulin Receptor	0.015	0.038	-9999	-0.38	4	4
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.014	0.1	-9999	-0.26	62	62
PRKCI	-0.032	0.1	-9999	-0.52	20	20
Insulin Receptor/Insulin/GRB14/PDK1	-0.099	0.12	-9999	-0.37	48	48
SHC1	0.017	0.023	-9999	-0.52	1	1
negative regulation of MAPKKK cascade	0.009	0.12	-9999	-0.67	12	12
PI3K	-0.005	0.11	-9999	-0.26	80	80
NCK2	0.015	0.027	-9999	-0.26	5	5
RHOQ	0.014	0.042	-9999	-0.46	4	4
mol:H2O2	-0.002	0.008	-9999	-10000	0	0
HRAS/GDP	0.009	0.037	-9999	-0.29	7	7
AKT2	-0.066	0.13	-9999	-0.36	42	42
PRKCZ	-0.026	0.066	-9999	-0.53	7	7
SH2B2	0	0	-9999	-10000	0	0
SHC/SHIP	-0.002	0.093	-9999	-0.25	63	63
F2RL2	-0.072	0.19	-9999	-0.44	103	103
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	0.019	0.04	-9999	-0.31	7	7
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.05	0.036	-9999	-0.38	2	2
RAPGEF1	0.018	0	-9999	-10000	0	0
RASA1	0.004	0.079	-9999	-0.42	16	16
NCK1	0.011	0.046	-9999	-0.28	12	12
CBL/APS/CAP/Crk-II	0.005	0.082	-9999	-0.28	34	34
TC10/GDP	0.011	0.03	-9999	-0.33	4	4
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	-0.68	12	12
INS	0.017	0.025	-9999	-0.52	1	1
mol:PI-3-4-P2	-0.013	0.095	-9999	-0.27	62	62
GRB2	0.016	0.024	-9999	-0.26	4	4
EIF4EBP1	-0.068	0.13	-9999	-0.34	57	57
PTPRA	0.017	0.028	-9999	-0.4	2	2
PIK3CA	0.016	0.029	-9999	-0.35	3	3
TC10/GTP/CIP4	0.019	0.04	-9999	-0.31	7	7
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	-0.36	3	3
Par3/Par6	-0.017	0.12	-9999	-0.27	84	84

×

E-cadherin signaling in keratinocytes

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
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	-0.018	0.11	-10000	0	-0.34	20	20
FMN1	-0.008	0.1	-10000	0	-0.24	78	78
mol:IP3	0.006	0.081	-10000	0	-0.25	23	23
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	0.093	-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	-0.35	3	3
mol:PI-4-5-P2	0	0.1	-10000	0	-0.33	10	10
VASP	-0.007	0.11	-10000	0	-0.36	14	14
ZYX	-0.006	0.11	-10000	0	-0.36	13	13
JUB	-0.023	0.13	-10000	0	-0.39	21	21
EGFR(dimer)	-0.042	0.13	-10000	0	-0.36	31	31
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	-0.35	3	3
PI3K	0.004	0.093	-10000	0	-0.26	28	28
FYN	0.016	0.084	-10000	0	-0.3	14	14
mol:Ca2+	0.006	0.08	-10000	0	-0.24	23	23
JUP	0.012	0.056	-10000	0	-0.42	8	8
PIK3R1	-0.008	0.11	-10000	0	-0.42	32	32
mol:DAG	0.006	0.081	-10000	0	-0.25	23	23
CDH1	-0.049	0.17	-10000	0	-0.48	71	71
RhoA/GDP	-0.024	0.12	-10000	0	-0.35	27	27
establishment of polarity of embryonic epithelium	-0.007	0.11	-10000	0	-0.36	14	14
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	-0.077	0.17	-10000	0	-0.35	136	136
CASR	0.013	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	-0.32	7	7
actin cable formation	-0.007	0.11	-10000	0	-0.36	14	14
apoptosis	-0.006	0.089	0.26	26	-10000	0	26
CTNNA1	0.017	0.024	-10000	0	-0.52	1	1
mol:GDP	-0.029	0.12	-10000	0	-0.36	21	21
PIP5K1A	-0.001	0.1	-10000	0	-0.34	10	10
PLCG1	0.006	0.082	-10000	0	-0.25	23	23
Rac1/GTP	-0.033	0.12	-10000	0	-0.33	30	30
homophilic cell adhesion	0	0.003	-10000	0	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.01	0.079	-9999	-0.26	31	31
STMN1	0.001	0.089	-9999	-0.38	22	22
Aurora B/RasGAP/Survivin	-0.012	0.12	-9999	-0.34	53	53
Chromosomal passenger complex/Cul3 protein complex	-0.054	0.14	-9999	-0.34	67	67
BIRC5	-0.039	0.16	-9999	-0.43	67	67
DES	-0.027	0.13	-9999	-0.68	16	16
Aurora C/Aurora B/INCENP	0.014	0.064	-9999	-0.29	15	15
Aurora B/TACC1	-0.004	0.086	-9999	-0.32	30	30
Aurora B/PP2A	0.019	0.043	-9999	-0.39	3	3
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.011	0.034	-9999	-0.21	9	9
mitotic metaphase/anaphase transition	0	0.005	-9999	-10000	0	0
NDC80	-0.015	0.12	-9999	-0.4	40	40
Cul3 protein complex	-0.049	0.14	-9999	-0.33	93	93
KIF2C	-0.062	0.24	-9999	-0.66	59	59
PEBP1	0.013	0.047	-9999	-0.53	4	4
KIF20A	-0.027	0.14	-9999	-0.47	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	0.053	-9999	-0.27	17	17
SMC2	0.003	0.079	-9999	-0.38	20	20
SMC4	0.014	0.041	-9999	-0.35	6	6
NSUN2/NPM1/Nucleolin	0.015	0.082	-9999	-0.87	3	3
PSMA3	0.017	0.012	-9999	-0.26	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	0.054	-9999	-0.27	18	18
CDCA8	-0.018	0.12	-9999	-0.41	44	44
cytokinesis	-0.05	0.26	-9999	-0.74	50	50
Aurora B/Septin1	-0.037	0.24	-9999	-0.71	45	45
AURKA	-0.012	0.11	-9999	-0.42	36	36
INCENP	-0.001	0.086	-9999	-0.38	23	23
KLHL13	-0.096	0.2	-9999	-0.39	147	147
BUB1	-0.051	0.17	-9999	-0.44	79	79
hSgo1/Aurora B/Survivin	-0.016	0.14	-9999	-0.39	52	52
EVI5	0.013	0.047	-9999	-0.52	4	4
RhoA/GTP	-0.047	0.25	-9999	-0.69	54	54
SGOL1	-0.01	0.11	-9999	-0.38	37	37
CENPA	-0.042	0.22	-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	0.011	0.041	-9999	-0.26	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	-0.007	0.11	-9999	-0.46	28	28
NPM1	0.012	0.052	-9999	-0.6	3	3
RASA1	0.004	0.079	-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	-0.054	0.28	-9999	-0.71	60	60
RhoA/GDP	0.004	0.058	-9999	-0.38	12	12
NSUN2	0.012	0.054	-9999	-0.6	3	3
MYLK	0.003	0.068	-9999	-0.33	19	19
KIF23	-0.025	0.14	-9999	-0.45	48	48
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	0.012	0.052	-9999	-0.6	3	3
Chromosomal passenger complex	-0.047	0.22	-9999	-0.59	56	56
Chromosomal passenger complex/EVI5	-0.014	0.15	-9999	-0.37	62	62
TACC1	-0.02	0.13	-9999	-0.41	47	47
PPP2R5D	0.016	0.021	-9999	-0.26	3	3
CUL3	0.01	0.061	-9999	-0.43	9	9
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

p75(NTR)-mediated 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	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	-0.026	0.13	-10000	0	-0.38	61	61
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	0.076	-10000	0	-0.29	12	12
NT-4/5 (dimer)/p75(NTR)	0.004	0.046	-10000	0	-0.2	23	23
IKBKB	0.011	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	0.092	-10000	0	-0.26	64	64
MGDIs/NGR/p75(NTR)/LINGO1	-0.004	0.087	-10000	0	-0.31	22	22
FURIN	0.003	0.077	-10000	0	-0.36	20	20
proBDNF (dimer)/p75(NTR)/Sortilin	0.003	0.076	-10000	0	-0.33	11	11
LINGO1	-0.02	0.097	-10000	0	-0.26	70	70
Sortilin/TRAF6/NRIF	-0.018	0.057	-10000	0	-0.34	5	5
proBDNF (dimer)	-0.016	0.092	-10000	0	-0.26	64	64
NTRK1	0.01	0.054	-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	-0.41	11	11
IRAK1	0.015	0.029	-10000	0	-0.26	6	6
SHC1	0.013	0.041	-10000	0	-0.31	4	4
ARHGDIA	0.016	0.029	-10000	0	-0.35	3	3
RhoA/GTP	0.004	0.058	-10000	0	-0.38	12	12
Gamma Secretase	0.032	0.07	-10000	0	-0.36	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.002	0.094	-10000	0	-0.3	42	42
MAGEH1	-0.018	0.13	-10000	0	-0.52	35	35
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.012	0.11	-10000	0	-0.3	64	64
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	-0.028	0.14	-10000	0	-0.42	55	55
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	0.058	-10000	0	-0.27	16	16
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	0.006	0.055	0.15	3	-0.26	10	13
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.026	0.041	-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	-0.015	0.089	-10000	0	-0.31	30	30
PSENEN	0.017	0.012	-10000	0	-0.26	1	1
mol:ceramide	0.014	0.056	-10000	0	-0.29	12	12
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.021	0.05	-10000	0	-0.26	1	1
p75(NTR)/beta APP	-0.016	0.11	-10000	0	-0.37	38	38
BEX1	-0.04	0.12	-10000	0	-0.26	108	108
mol:GDP	0.002	0.038	-10000	0	-0.32	3	3
NGF (dimer)	-0.038	0.13	-10000	0	-0.29	99	99
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.008	0.082	-10000	0	-0.28	23	23
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
RAC1/GTP	0.014	0.033	-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	-0.015	0.089	-10000	0	-0.31	30	30
RHOB	-0.04	0.17	-10000	0	-0.52	57	57
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	0.1	-10000	0	-0.28	67	67
TP53	-0.001	0.098	-10000	0	-0.28	38	38
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	-0.35	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	0.096	-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	0.096	-10000	0	-0.51	18	18
APH1A	0.003	0.068	-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	0.089	-10000	0	-0.41	12	12
MAPK8	0.014	0.08	-10000	0	-0.29	8	8
MAPK9	0.005	0.097	-10000	0	-0.31	20	20
APAF1	0.012	0.051	-10000	0	-0.41	7	7
NTF3	-0.021	0.1	-10000	0	-0.28	67	67
NTF4	0	0	-10000	0	-10000	0	0
NDN	-0.044	0.17	-10000	0	-0.49	64	64
RAC1/GDP	0.013	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.028	0.11	-10000	0	-0.25	95	95
p75 CTF/Sortilin/TRAF6/NRIF	0.036	0.048	-10000	0	-0.27	10	10
RhoA-B-C/GTP	-0.015	0.088	-10000	0	-0.31	30	30
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	-0.035	0.14	-10000	0	-0.34	78	78
proBDNF (dimer)/p75 ECD	0.002	0.065	-10000	0	-0.35	2	2
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.086	0.19	-10000	0	-0.41	129	129
BIRC2	0.016	0.021	-10000	0	-0.26	3	3
neuron projection morphogenesis	-0.032	0.11	0.2	2	-0.34	35	37
BAD	0.008	0.091	-10000	0	-0.3	16	16
RIPK2	0.013	0.041	-10000	0	-0.29	9	9
NGFR	0.004	0.066	-10000	0	-0.29	23	23
CYCS	0.009	0.074	-10000	0	-0.25	34	34
ADAM17	0.016	0.024	-10000	0	-0.26	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	-0.3	15	15
BDNF (dimer)/p75(NTR)	-0.006	0.076	-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	0.051	-10000	0	-0.28	10	10
NDNL2	0.018	0	-10000	0	-10000	0	0
YWHAE	0.016	0.029	-10000	0	-0.35	3	3
PRKCI	0.001	0.088	-10000	0	-0.44	19	19
NGF (dimer)/p75(NTR)	0.004	0.046	-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	-0.28	18	18
SQSTM1	0.012	0.053	-10000	0	-0.48	6	6
NGFRAP1	-0.056	0.18	-10000	0	-0.51	73	73
CASP3	0.01	0.087	-10000	0	-0.28	14	14
E2F1	0.006	0.071	-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	0.038	-10000	0	-0.22	12	12
MMP7	-0.094	0.21	-10000	0	-0.44	128	128
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.028	0.054	-10000	0	-0.25	13	13
MMP3	-0.13	0.22	-10000	0	-0.43	173	173
APAF-1/Caspase 9	-0.046	0.077	-10000	0	-0.31	10	10

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.013	0.11	-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	-0.012	0.15	-10000	0	-0.47	27	27
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.014	0.063	-10000	0	-0.35	11	11
antigen processing and presentation of peptide antigen via MHC class I	-0.056	0.1	-10000	0	-0.31	54	54
CaM/Ca2+	-0.008	0.098	-10000	0	-0.32	16	16
RAP1A	0.011	0.062	-10000	0	-0.52	7	7
STAT1 (dimer)/SHP2	-0.028	0.13	-10000	0	-0.37	35	35
AKT1	-0.012	0.11	-10000	0	-0.36	19	19
MAP2K1	-0.025	0.12	-10000	0	-0.35	33	33
MAP3K11	-0.012	0.099	-10000	0	-0.33	18	18
IFNGR1	0.01	0.04	-10000	0	-0.31	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.029	0.14	-10000	0	-0.39	44	44
Rap1/GTP	-0.031	0.07	-10000	0	-0.41	7	7
CRKL/C3G	0.023	0.034	-10000	0	-0.37	4	4
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.01	0.11	-10000	0	-0.31	23	23
CEBPB	-0.011	0.16	-10000	0	-0.45	33	33
STAT3	0.015	0.04	-10000	0	-0.52	3	3
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0	0.11	-10000	0	-0.67	4	4
STAT1	-0.03	0.13	-10000	0	-0.36	37	37
CALM1	0.018	0	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.087	0.17	-10000	0	-0.33	161	161
PIK3CA	0.016	0.029	-10000	0	-0.35	3	3
STAT1 (dimer)/PIAS1	-0.02	0.12	-10000	0	-0.4	25	25
CEBPB/PTGES2/Cbp/p300	-0.044	0.11	-10000	0	-0.4	28	28
mol:Ca2+	-0.015	0.1	-10000	0	-0.26	57	57
MAPK3	-0.017	0.14	-10000	0	-0.44	21	21
STAT1 (dimer)	-0.071	0.15	-10000	0	-0.44	54	54
MAPK1	-0.018	0.14	-10000	0	-0.51	15	15
JAK2	0.006	0.057	-10000	0	-0.34	12	12
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
JAK1	0.008	0.059	-10000	0	-0.54	6	6
CAMK2D	-0.004	0.098	-10000	0	-0.4	28	28
DAPK1	-0.001	0.14	-10000	0	-0.47	24	24
SMAD7	0.004	0.073	-10000	0	-0.19	17	17
CBL/CRKL/C3G	0.005	0.096	-10000	0	-0.36	10	10
PI3K	-0.022	0.11	-10000	0	-0.36	21	21
IFNG	-0.087	0.17	-10000	0	-0.33	161	161
apoptosis	-0.008	0.12	0.27	2	-0.35	28	30
CAMK2G	0.017	0.017	-10000	0	-0.26	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	-0.079	0.18	-10000	0	-0.37	133	133
FRAP1	-0.005	0.1	-10000	0	-0.35	15	15
PRKCD	-0.011	0.11	-10000	0	-0.36	19	19
RAP1B	0.013	0.044	-10000	0	-0.32	8	8
negative regulation of cell growth	-0.056	0.1	-10000	0	-0.31	54	54
PTPN2	0.016	0.024	-10000	0	-0.26	4	4
EP300	0.014	0.047	-10000	0	-0.52	4	4
IRF1	-0.009	0.16	-10000	0	-0.48	36	36
STAT1 (dimer)/PIASy	-0.025	0.13	-10000	0	-0.42	25	25
SOCS1	0.009	0.064	-10000	0	-1.4	1	1
mol:GDP	0.003	0.092	-10000	0	-0.34	10	10
CASP1	-0.017	0.12	-10000	0	-0.28	67	67
PTGES2	0.017	0.012	-10000	0	-0.26	1	1
IRF9	0.016	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	-0.032	0.072	-10000	0	-0.43	7	7
CBL	-0.011	0.098	-10000	0	-0.33	16	16
MAP3K1	-0.034	0.13	-10000	0	-0.34	43	43
PIAS1	0.017	0.012	-10000	0	-0.26	1	1
PIAS4	0.012	0.05	-10000	0	-0.43	6	6
antigen processing and presentation of peptide antigen via MHC class II	-0.056	0.1	-10000	0	-0.31	54	54
PTPN11	-0.02	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 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
STX1A	0.009	0.028	-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	-0.26	2	2
ACh/CHRNA1	0.008	0.046	-9999	-0.3	9	9
RAB3GAP2/RIMS1/UNC13B	0.019	0.055	-9999	-0.33	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	-0.004	0.074	-9999	-0.26	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	-0.26	2	2
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	0.008	0.046	-9999	-0.29	9	9
UNC13B	0.011	0.048	-9999	-0.31	11	11
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	264	264
SNAP25	-0.008	0.056	-9999	-0.29	15	15
VAMP2	0.007	0.011	-9999	-0.26	1	1
SYT1	-0.17	0.21	-9999	-0.36	264	264
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	-0.26	2	2

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.017	0.13	-10000	0	-0.49	37	37
HRAS	0.012	0.051	-10000	0	-0.41	7	7
EGFR	-0.077	0.17	-10000	0	-0.35	136	136
AKT	0.015	0.077	-10000	0	-0.32	15	15
FOXO3	0.011	0.054	-10000	0	-0.38	9	9
AKT1	0.011	0.054	-10000	0	-0.38	9	9
FOXO1	0.001	0.089	-10000	0	-0.46	18	18
AKT3	-0.006	0.082	-10000	0	-0.28	42	42
FOXO4	0.017	0.023	-10000	0	-0.52	1	1
MET	-0.001	0.078	-10000	0	-0.3	31	31
PIK3CA	0.016	0.029	-10000	0	-0.35	3	3
PIK3CB	0.012	0.055	-10000	0	-0.45	7	7
NRAS	0.006	0.072	-10000	0	-0.4	15	15
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	0.096	0.21	1	-0.26	50	51
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	0.098	0.18	4	-0.24	62	66
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
KRAS	0.008	0.069	-10000	0	-0.45	11	11
FOXO	0.039	0.037	-10000	0	-0.18	2	2
AKT2	0.017	0.012	-10000	0	-0.26	1	1
PTEN	-0.002	0.1	-10000	0	-0.52	19	19

×

FOXA2 and FOXA3 transcription factor networks

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	0.018	0.27	-9999	-0.76	29	29
PCK1	0.018	0.2	-9999	-0.95	6	6
HNF4A	0.032	0.27	-9999	-0.84	14	14
KCNJ11	-0.016	0.38	-9999	-1	49	49
AKT1	0.01	0.17	-9999	-0.44	27	27
response to starvation	0.006	0.003	-9999	-10000	0	0
DLK1	0.018	0.3	-9999	-0.78	29	29
NKX2-1	0.074	0.14	-9999	-0.49	1	1
ACADM	0.01	0.29	-9999	-0.77	36	36
TAT	0.017	0.18	-9999	-0.57	5	5
CEBPB	0.01	0.072	-9999	-0.33	20	20
CEBPA	0.011	0.085	-9999	-0.5	14	14
TTR	-0.041	0.28	-9999	-0.76	39	39
PKLR	0.022	0.26	-9999	-0.73	26	26
APOA1	0.031	0.3	-9999	-0.91	15	15
CPT1C	-0.001	0.3	-9999	-0.83	37	37
ALAS1	0.038	0.19	-9999	-1.6	2	2
TFRC	-0.045	0.39	-9999	-1.1	46	46
FOXF1	-0.003	0.066	-9999	-0.32	20	20
NF1	0.023	0.039	-9999	-0.46	3	3
HNF1A (dimer)	0.03	0.048	-9999	-0.23	10	10
CPT1A	0.005	0.3	-9999	-0.84	34	34
HMGCS1	0.017	0.27	-9999	-0.74	27	27
NR3C1	0.005	0.11	-9999	-0.5	21	21
CPT1B	0.021	0.26	-9999	-0.74	26	26
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.02	0.04	-9999	-0.3	4	4
GCK	0.016	0.27	-9999	-0.73	31	31
CREB1	0.02	0.036	-9999	-0.36	2	2
IGFBP1	0.026	0.16	-9999	-0.73	4	4
PDX1	0.034	0.26	-9999	-1.1	15	15
UCP2	-0.026	0.35	-9999	-0.89	53	53
ALDOB	0.023	0.29	-9999	-0.78	28	28
AFP	-0.049	0.15	-9999	-0.45	20	20
BDH1	0.01	0.28	-9999	-0.74	36	36
HADH	0.02	0.3	-9999	-0.8	30	30
F2	0.031	0.3	-9999	-0.92	14	14
HNF1A	0.03	0.048	-9999	-0.23	10	10
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	-0.5	106	106
FOXA3	-0.015	0.13	-9999	-0.38	30	30
FOXA2	0.031	0.35	-9999	-0.86	32	32
ABCC8	-0.2	0.52	-9999	-0.9	170	170
ALB	-0.055	0.17	-9999	-0.67	16	16

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.18	-9999	-0.44	67	67
MED1	0	0.068	-9999	-0.26	34	34
mol:9cRA	-0.001	0.021	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.005	0.11	-9999	-0.28	64	64
RXRs/NUR77	0.03	0.077	-9999	-0.28	20	20
RXRs/PPAR	0.009	0.09	-9999	-0.31	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	0.003	0.097	-9999	-0.27	50	50
RARA	0.007	0.07	-9999	-0.43	12	12
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	0.004	0.08	-9999	-0.27	32	32
RARG	0.017	0.023	-9999	-0.52	1	1
RPS6KB1	0.004	0.055	-9999	-0.4	1	1
RARs/THRs/DNA/SMRT	-0.002	0.11	-9999	-0.27	59	59
THRA	-0.011	0.11	-9999	-0.39	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	0.085	-9999	-0.29	19	19
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	0.009	0.071	-9999	-0.44	11	11
RXRs/VDR/DNA/Vit D3	0.02	0.089	-9999	-0.26	38	38
NR4A1	0.009	0.05	-9999	-0.28	15	15
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.016	0.064	-9999	-0.26	9	9
RXRG	0.003	0.087	-9999	-0.47	16	16
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	-0.035	0.13	-9999	-0.34	79	79
PPARD	0.017	0.017	-9999	-0.26	2	2
TNF	-0.01	0.23	-9999	-0.82	27	27
mol:Oxysterols	0	0.018	-9999	-10000	0	0
cholesterol transport	0	0.18	-9999	-0.44	67	67
PPARA	0.013	0.041	-9999	-0.29	9	9
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.025	0.13	-9999	-0.36	60	60
RXRs/NUR77/BCL2	-0.041	0.12	-9999	-0.3	40	40
SREBF1	-0.051	0.33	-9999	-1	51	51
RXRs/RXRs/DNA/9cRA	0.022	0.085	-9999	-0.29	19	19
ABCA1	-0.008	0.24	-9999	-0.82	28	28
RARs/THRs	-0.001	0.12	-9999	-0.29	61	61
RXRs/FXR	0.033	0.075	-9999	-0.28	21	21
BCL2	-0.12	0.22	-9999	-0.47	145	145

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.016	0.033	-9999	-0.52	2	2
SPHK1	-0.027	0.14	-9999	-0.42	54	54
GNAI2	0.006	0.075	-9999	-0.48	12	12
mol:S1P	-0.001	0.088	-9999	-0.3	36	36
GNAO1	0.016	0.024	-9999	-0.26	4	4
mol:Sphinganine-1-P	-0.008	0.1	-9999	-0.38	34	34
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.014	0.076	-9999	-0.23	40	40
GNAI3	0.017	0.023	-9999	-0.52	1	1
G12/G13	0.02	0.043	-9999	-0.37	5	5
S1PR3	0	0	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	-0.021	0.13	-9999	-0.41	48	48
S1P1/S1P	-0.014	0.11	-9999	-0.29	60	60
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
GNAI1	-0.015	0.12	-9999	-0.38	44	44
S1P/S1P5/G12	0.007	0.07	-9999	-0.23	36	36
S1P/S1P3/Gq	-0.027	0.11	-9999	-0.28	67	67
S1P/S1P4/Gi	0.007	0.09	-9999	-0.39	13	13
GNAQ	0	0	-9999	-10000	0	0
GNAZ	0.002	0.085	-9999	-0.43	18	18
GNA14	-0.081	0.18	-9999	-0.35	141	141
GNA15	0.001	0.078	-9999	-0.33	25	25
GNA12	0.018	0	-9999	-10000	0	0
GNA13	0.009	0.059	-9999	-0.38	11	11
GNA11	0.014	0.047	-9999	-0.52	4	4
ABCC1	0.012	0.051	-9999	-0.41	7	7

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.001	0.051	0.24	19	-10000	0	19
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	-0.054	41	41
KIF2A	0.005	0.054	-10000	0	-0.28	10	10
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	0.095	-10000	0	-0.31	41	41
WEE1	-0.003	0.093	-10000	0	-0.32	31	31
cytokinesis	-0.026	0.16	-10000	0	-0.51	45	45
PP2A-alpha B56	-0.058	0.27	-10000	0	-0.76	61	61
AURKA	-0.002	0.064	-10000	0	-0.28	23	23
PICH/PLK1	-0.024	0.18	-10000	0	-0.46	57	57
CENPE	-0.011	0.097	-10000	0	-0.32	39	39
RhoA/GTP	0.004	0.058	-10000	0	-0.38	12	12
positive regulation of microtubule depolymerization	0.005	0.054	-10000	0	-0.28	10	10
PPP2CA	0.011	0.062	-10000	0	-0.52	7	7
FZR1	0.018	0	-10000	0	-10000	0	0
TPX2	-0.013	0.084	-10000	0	-0.29	41	41
PAK1	-0.023	0.13	-10000	0	-0.38	53	53
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	-0.35	11	11
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	-0.054	41	41
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	-0.86	59	59
TPT1	0.009	0.019	-10000	0	-10000	0	0
CDC25C	-0.017	0.11	-10000	0	-0.44	34	34
CDC25B	0.003	0.07	-10000	0	-0.31	23	23
SGOL1	-0.001	0.051	-10000	0	-0.24	19	19
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	-0.38	51	51
PLK1/PBIP1	-0.011	0.083	-10000	0	-0.27	40	40
mitosis	0.002	0.007	0.035	21	-10000	0	21
FBXO5	0.003	0.054	-10000	0	-0.25	11	11
CDC2	-0.012	0.12	-10000	0	-0.45	34	34
NDC80	-0.03	0.14	-10000	0	-0.42	58	58
metaphase plate congression	0.009	0.023	-10000	0	-10000	0	0
ERCC6L	-0.027	0.19	-10000	0	-0.56	47	47
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	0.011	5	-10000	0	5
PPP1R12A	0.015	0.031	-10000	0	-0.32	4	4
interphase	0	0.002	0.011	5	-10000	0	5
PLK1/PRC1-2	-0.018	0.14	-10000	0	-0.42	49	49
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	21	21
mitotic prometaphase	0	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.057	-10000	0	-0.32	6	6
microtubule-based process	-0.011	0.1	-10000	0	-0.34	40	40
Golgi organization	0.002	0.041	-10000	0	-0.12	46	46
Cohesin/SA2	0.01	0.036	-10000	0	-0.13	15	15
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	-0.32	30	30
PPP2R1A	0.017	0.012	-10000	0	-0.26	1	1
chromosome segregation	-0.011	0.082	-10000	0	-0.27	40	40
PRC1	-0.02	0.13	-10000	0	-0.43	44	44
ECT2	-0.001	0.07	-10000	0	-0.28	22	22
C13orf34	0.006	0.037	-10000	0	-0.13	17	17
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	0.032	-10000	0	-0.094	27	27
spindle stabilization	0.002	0.019	-10000	0	-0.053	41	41
APC/C/HCDH1	0.02	0.025	-10000	0	-0.32	3	3
MKLP2/PLK1	-0.011	0.1	-10000	0	-0.34	40	40
CCNB1	-0.016	0.13	-10000	0	-0.5	35	35
PPP1CB	0.016	0.021	-10000	0	-0.26	3	3
BTRC	0.009	0.054	-10000	0	-0.29	15	15
ROCK2	0.007	0.057	-10000	0	-0.34	8	8
TUBG1	0.008	0.021	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.046	0.14	-10000	0	-0.48	41	41
MLF1IP	-0.018	0.1	-10000	0	-0.32	49	49
INCENP	0	0.085	-10000	0	-0.38	23	23

×

Regulation of Androgen receptor activity

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
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	-0.026	0.13	-9999	-0.4	29	29
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	0.001	0.084	-9999	-0.38	20	20
FOXO1	0.002	0.089	-9999	-0.46	18	18
T-DHT/AR	-0.019	0.15	-9999	-0.42	29	29
MAP2K6	-0.013	0.11	-9999	-0.4	37	37
BRM/BAF57	0.026	0.023	-9999	-0.37	1	1
MAP2K4	-0.007	0.1	-9999	-0.39	30	30
SMARCA2	0.017	0.023	-9999	-0.52	1	1
PDE9A	-0.024	0.15	-9999	-0.86	8	8
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	0.14	-9999	-0.37	20	20
NR0B1	-0.01	0.087	-9999	-0.27	50	50
EGR1	-0.1	0.2	-9999	-0.39	155	155
RXRs/9cRA	0.024	0.059	-9999	-0.28	19	19
AR/RACK1/Src	0.003	0.1	-9999	-0.34	20	20
AR/GR	-0.039	0.13	-9999	-0.29	76	76
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	0.079	-9999	-0.38	18	18
T-DHT/AR/TIF2/CARM1	0	0.11	-9999	-0.36	22	22
SRC	0.005	0.09	-9999	-0.31	21	21
NR3C1	-0.003	0.1	-9999	-0.51	21	21
KLK3	-0.038	0.11	-9999	-0.48	5	5
APPBP2	0.009	0.043	-9999	-0.26	13	13
TRIM24	0.017	0.024	-9999	-0.26	4	4
T-DHT/AR/TIP60	-0.021	0.1	-9999	-0.31	42	42
TMPRSS2	-0.18	0.43	-9999	-1.1	97	97
RXRG	0.003	0.086	-9999	-0.47	16	16
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	0.021	-9999	-0.26	3	3
KLK2	0.021	0.095	-9999	-0.4	4	4
AR	-0.04	0.13	-9999	-0.27	114	114
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	-0.44	18	18
GATA2	-0.008	0.094	-9999	-0.32	40	40
MYST2	0.011	0.047	-9999	-0.31	10	10
HOXB13	-0.075	0.13	-9999	-0.26	182	182
T-DHT/AR/RACK1/Src	-0.002	0.11	-9999	-0.35	20	20
positive regulation of transcription	-0.008	0.093	-9999	-0.32	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	0.01	0.08	-9999	-0.32	8	8
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	-0.35	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	25	25
CREBBP	0.016	0.033	-9999	-0.52	2	2
SMARCE1	0.017	0.021	-9999	-0.26	3	3

×

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	-0.001	0.11	-9999	-0.36	32	32
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	-0.003	0.15	-9999	-0.57	20	20
GNAO1	0.016	0.024	-9999	-0.26	4	4
PDGFB-D/PDGFRB/PLCgamma1	0.007	0.14	-9999	-0.52	20	20
PLCG1	0.003	0.14	-9999	-0.52	20	20
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	0.017	0.024	-9999	-0.53	1	1
GNAI1	-0.015	0.12	-9999	-0.38	44	44
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.015	0.16	-9999	-0.64	28	28
S1P1/S1P	-0.029	0.19	-9999	-0.52	57	57
negative regulation of cAMP metabolic process	-0.002	0.15	-9999	-0.55	20	20
MAPK3	0.001	0.16	-9999	-0.58	20	20
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	0.005	0.077	-9999	-0.65	5	5
PLCB2	-0.017	0.17	-9999	-0.45	57	57
RAC1	0.018	0	-9999	-10000	0	0
RhoA/GTP	-0.062	0.14	-9999	-0.42	60	60
receptor internalization	-0.026	0.18	-9999	-0.48	57	57
PTGS2	-0.002	0.18	-9999	-0.79	12	12
Rac1/GTP	-0.058	0.14	-9999	-0.42	57	57
RHOA	0.005	0.08	-9999	-0.52	12	12
VEGFA	-0.007	0.086	-9999	-0.3	31	31
negative regulation of T cell proliferation	-0.002	0.15	-9999	-0.55	20	20
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.003	0.085	-9999	-0.44	18	18
MAPK1	0	0.16	-9999	-0.58	20	20
S1P1/S1P/PDGFB-D/PDGFRB	-0.019	0.2	-9999	-0.59	40	40
ABCC1	0.012	0.051	-9999	-0.41	7	7

×

Atypical NF-kappaB pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.02	0.049	-9999	-0.37	8	8
FBXW11	0.015	0.035	-9999	-0.43	3	3
NF kappa B1 p50/c-Rel	0.018	0.063	-9999	-0.31	15	15
NF kappa B1 p50/RelA/I kappa B alpha	0.001	0.11	-9999	-0.44	17	17
NFKBIA	-0.023	0.12	-9999	-0.25	86	86
MAPK14	0.017	0.012	-9999	-0.26	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	0.052	-9999	-0.3	11	11
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	-0.35	3	3
NF kappa B1 p50 dimer	0.019	0.037	-9999	-0.37	3	3
PIK3R1	-0.009	0.11	-9999	-0.42	32	32
NFKB1	0.02	0.037	-9999	-0.37	3	3
RELA	0.018	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	-0.013	0.1	-9999	-0.23	84	84
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.006	0.11	-9999	-0.44	16	16
SRC	0.015	0.035	-9999	-0.43	3	3
PI3K	0.006	0.082	-9999	-0.37	21	21
NF kappa B1 p50/RelA	-0.013	0.1	-9999	-0.23	84	84
IKBKB	0.011	0.047	-9999	-0.31	10	10
beta TrCP1/SCF ubiquitin ligase complex	0.015	0.035	-9999	-0.43	3	3
SYK	-0.022	0.14	-9999	-0.48	42	42
I kappa B alpha/PIK3R1	-0.026	0.12	-9999	-0.37	38	38
cell death	0.006	0.1	-9999	-0.42	16	16
NF kappa B1 p105/c-Rel	0.018	0.063	-9999	-0.31	15	15
LCK	-0.073	0.18	-9999	-0.4	115	115
BCL3	0.009	0.067	-9999	-0.49	9	9

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.042	0.17	-10000	0	-0.9	12	12
NCK1/PAK1/Dok-R	-0.032	0.083	-10000	0	-0.46	11	11
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	0.053	0.15	-10000	0	-0.9	11	11
FN1	-0.046	0.17	-10000	0	-0.46	71	71
PLD2	0.038	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	-0.37	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	-0.38	53	53
Tie2/Ang1/alpha5/beta1 Integrin	0.023	0.19	-10000	0	-1	11	11
CDKN1A	0.022	0.2	-10000	0	-0.76	27	27
ITGA5	0.014	0.042	-10000	0	-0.46	4	4
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	0.051	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	0.049	0.16	-10000	0	-0.87	11	11
GRB2	0.016	0.024	-10000	0	-0.26	4	4
PIK3R1	-0.008	0.11	-10000	0	-0.42	32	32
ANGPT2	-0.018	0.16	-10000	0	-0.64	15	15
BMX	0.012	0.19	-10000	0	-1.2	11	11
ANGPT1	0.021	0.085	-10000	0	-1.2	1	1
tube development	0.027	0.17	-10000	0	-0.74	16	16
ANGPT4	0.016	0.035	-10000	0	-0.43	3	3
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	121	121
STAT5A (dimer)	0.027	0.2	-10000	0	-0.78	25	25
mol:L-citrulline	0.051	0.14	-10000	0	-0.66	12	12
AGTR1	-0.15	0.21	-10000	0	-0.36	229	229
MAPK14	0.035	0.18	-10000	0	-1.1	11	11
Tie2/SHP2	0.027	0.16	-10000	0	-1.1	10	10
TEK	0.025	0.18	-10000	0	-1.2	10	10
RPS6KB1	0.041	0.16	-10000	0	-0.88	11	11
Angiotensin II/AT1	-0.099	0.15	-10000	0	-0.25	229	229
Tie2/Ang1/GRB2	0.041	0.16	-10000	0	-1	11	11
MAPK3	0.043	0.15	-10000	0	-0.92	11	11
MAPK1	0.043	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	0.039	0.16	-10000	0	-1	11	11
PI3K	0.036	0.19	-10000	0	-1.1	11	11
FES	0.032	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	0.044	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	0.044	0.16	-10000	0	-0.88	11	11
Tie2/Ang2	0.017	0.21	-10000	0	-1	15	15
Tie2/Ang1	0.035	0.17	-10000	0	-1.1	11	11
FOXO1	0.044	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	18	18
FYN	0.024	0.19	-10000	0	-0.85	16	16
DOK2	-0.021	0.13	-10000	0	-0.41	48	48
negative regulation of cell cycle	0.026	0.18	-10000	0	-0.67	27	27
ETS1	0.012	0.072	-10000	0	-0.3	23	23
PXN	0.051	0.14	-10000	0	-0.72	11	11
ITGB1	0.015	0.037	-10000	0	-0.39	4	4
NOS3	0.05	0.15	-10000	0	-0.75	12	12
RAC1	0.018	0	-10000	0	-10000	0	0
TNF	0.004	0.098	-10000	0	-0.43	19	19
MAPKKK cascade	0.038	0.16	-10000	0	-0.96	11	11
RASA1	0.004	0.079	-10000	0	-0.42	16	16
Tie2/Ang1/Shc	0.042	0.16	-10000	0	-1	11	11
NCK1	0.011	0.046	-10000	0	-0.28	12	12
vasculogenesis	0.052	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	0.051	0.14	-10000	0	-0.66	12	12
Rac1/GTP	-0.011	0.14	-10000	0	-0.82	11	11
MMP2	0.017	0.19	-10000	0	-1.1	11	11

×

Arf6 downstream 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
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	0.25	39	-10000	0	39
ARF1/GTP	0.012	0.05	-10000	0	-0.28	4	4
mol:GM1	0	0.047	-10000	0	-0.25	4	4
mol:Choline	0.008	0.074	-10000	0	-0.34	15	15
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	0.018	0.083	-10000	0	-0.25	39	39
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	-0.35	3	3
TIAM1	0.006	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	0.002	0.11	0.35	41	-10000	0	41
KALRN	-0.022	0.078	-10000	0	-0.3	34	34
RAB11FIP3/RAB11A	0.019	0.05	-10000	0	-0.37	8	8
RhoA/GDP	-0.002	0.11	-10000	0	-0.36	41	41
NME1	0.012	0.04	-10000	0	-0.26	11	11
Rac1/GDP	0.004	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	0.073	-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	0.077	-10000	0	-0.38	12	12
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	-0.35	7	7
PIP5K1A	0.012	0.065	-10000	0	-0.35	8	8
mol:Phosphatidic acid	0.008	0.074	-10000	0	-0.34	15	15
Rac1/GTP	-0.002	0.11	-10000	0	-0.43	32	32

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.049	0.26	-10000	0	-1.2	26	26
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	0.036	0.13	-10000	0	-0.37	22	22
EPO	0.053	0.23	-10000	0	-0.55	30	30
FIH (dimer)	0.024	0.027	-10000	0	-0.52	1	1
APEX1	0.025	0.019	-10000	0	-0.26	1	1
SERPINE1	0.054	0.25	-10000	0	-0.66	34	34
FLT1	-0.019	0.18	-10000	0	-1.1	13	13
ADORA2A	0.042	0.24	-10000	0	-0.63	35	35
germ cell development	0.068	0.22	-10000	0	-0.59	29	29
SLC11A2	0.066	0.23	-10000	0	-0.62	30	30
BHLHE40	0.059	0.23	-10000	0	-0.6	31	31
HIF1AN	0.024	0.027	-10000	0	-0.52	1	1
HIF2A/ARNT/SIRT1	0.041	0.17	-10000	0	-0.42	30	30
ETS1	0.019	0.072	-10000	0	-0.3	23	23
CITED2	-0.013	0.15	-10000	0	-1.1	9	9
KDR	-0.008	0.15	-10000	0	-1.1	8	8
PGK1	0.068	0.23	-10000	0	-0.6	29	29
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	0.085	0.27	-10000	0	-0.71	30	30
EPAS1	0.02	0.15	-10000	0	-0.37	35	35
SP1	0.023	0.027	-10000	0	-0.52	1	1
ABCG2	0.06	0.24	-10000	0	-0.65	33	33
EFNA1	0.058	0.24	-10000	0	-0.6	38	38
FXN	0.059	0.22	-10000	0	-0.63	25	25
POU5F1	0.068	0.23	-10000	0	-0.61	29	29
neuron apoptosis	-0.084	0.26	0.68	30	-10000	0	30
EP300	0.014	0.047	-10000	0	-0.52	4	4
EGLN3	-0.066	0.19	-10000	0	-0.4	116	116
EGLN2	0.018	0.055	-10000	0	-0.36	9	9
EGLN1	0.009	0.083	-10000	0	-0.36	23	23
VHL/Elongin B/Elongin C	0.032	0.028	-10000	0	-0.3	1	1
VHL	0.014	0.031	-10000	0	-0.26	7	7
ARNT	0.025	0.014	-10000	0	-10000	0	0
SLC2A1	0.053	0.23	-10000	0	-0.61	33	33
TWIST1	0.038	0.27	-10000	0	-0.66	45	45
ELK1	0.022	0.038	-10000	0	-0.39	4	4
HIF2A/ARNT/Cbp/p300	0.054	0.17	-10000	0	-0.44	26	26
VEGFA	0.06	0.24	-10000	0	-0.61	31	31
CREBBP	0.016	0.033	-10000	0	-0.52	2	2

×

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	23	23
BIRC5	-0.037	0.15	-9999	-0.42	67	67
NFKBIA	0.024	0.054	-9999	-0.33	3	3
CPEB1	0.004	0.068	-9999	-0.31	22	22
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	-0.012	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	0.01	0.044	-9999	-0.26	14	14
JUB	-0.027	0.15	-9999	-0.49	47	47
TPX2	-0.01	0.11	-9999	-0.37	41	41
TP53	0.004	0.089	-9999	-0.29	37	37
DLG7	-0.006	0.11	-9999	-0.35	43	43
AURKAIP1	0.016	0.029	-9999	-0.35	3	3
ARHGEF7	0.016	0.021	-9999	-0.26	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	-0.21	21	21
AURKB	-0.007	0.078	-9999	-0.22	47	47
CDC25B	0.011	0.069	-9999	-0.37	5	5
G2/M transition checkpoint	-0.002	0.088	-9999	-0.27	42	42
mRNA polyadenylation	0.016	0.053	-9999	-0.26	5	5
Aurora A/CPEB	0.016	0.053	-9999	-0.26	5	5
Aurora A/TACC1/TRAP/chTOG	0.017	0.092	-9999	-0.27	33	33
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	0.016	0.09	-9999	-0.27	33	33
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	47	47
Aurora A/PP2A	0.025	0.047	-9999	-0.21	1	1
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	0.029	-9999	-0.37	1	1
RASA1	0.004	0.079	-9999	-0.42	16	16
Ajuba/Aurora A	-0.002	0.089	-9999	-0.27	42	42
mitotic prometaphase	-0.001	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.058	-9999	-0.21	21	21
TACC1	-0.02	0.13	-9999	-0.41	47	47
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	-0.26	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	-0.01	0.11	-9999	-0.37	41	41
PPP2R5D	0.016	0.021	-9999	-0.26	3	3
Aurora A/TPX2	0.006	0.1	-9999	-0.4	26	26
PAK1	-0.022	0.13	-9999	-0.38	53	53
CKAP5	0.017	0.017	-9999	-0.26	2	2

×

mTOR signaling 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
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	71	79
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	-0.24	28	28
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	15	15
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	-0.2	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.017	0.012	-10000	0	-0.26	1	1
RPS6KB1	0.011	0.065	0.19	8	-0.26	5	13
MAP3K5	-0.013	0.088	-10000	0	-0.36	29	29
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
apoptosis	-0.013	0.088	-10000	0	-0.36	29	29
mol:LY294002	0	0.001	0.001	1	-0.001	57	58
EIF4B	0.016	0.062	0.18	8	-0.24	7	15
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	0.033	0.054	0.18	8	-0.3	2	10
FKBP1A	0.017	0.017	-10000	0	-0.26	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	0.012	-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	-0.01	0.14	-10000	0	-0.59	29	29
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	-0.019	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	-0.35	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	6	21
EEF2	0.025	0.031	-10000	0	-0.28	5	5
eIF4E/4E-BP1	-0.001	0.14	-10000	0	-1	10	10

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.008	0.13	-10000	0	-0.51	12	12
BAG4	0.002	0.071	-10000	0	-0.29	28	28
BAD	0.011	0.045	-10000	0	-0.18	9	9
NFKBIA	0.014	0.042	-10000	0	-0.46	4	4
BIRC3	-0.086	0.19	-10000	0	-0.41	129	129
BAX	0.011	0.045	-10000	0	-0.19	7	7
EnzymeConsortium:3.1.4.12	0.001	0.031	-10000	0	-0.087	22	22
IKBKB	-0.003	0.12	-10000	0	-0.44	16	16
MAP2K2	0.022	0.047	-10000	0	-0.24	6	6
MAP2K1	0.023	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	-0.003	0.12	-10000	0	-0.42	19	19
MAP2K4	-0.011	0.09	-10000	0	-0.24	56	56
protein ubiquitination	-0.002	0.12	-10000	0	-0.44	15	15
EnzymeConsortium:2.7.1.37	0.02	0.052	-10000	0	-0.26	4	4
response to UV	0	0	-10000	0	-0.002	4	4
RAF1	0.018	0.044	-10000	0	-0.22	4	4
CRADD	0.009	0.067	-10000	0	-0.49	9	9
mol:ceramide	0.005	0.046	-10000	0	-0.16	14	14
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	0.084	-10000	0	-0.24	46	46
TRADD	0.016	0.026	-10000	0	-0.39	2	2
RELA/p50	0.018	0	-10000	0	-10000	0	0
MAPK3	0.026	0.044	-10000	0	-0.22	3	3
MAPK1	0.026	0.044	-10000	0	-0.21	4	4
p50/RELA/I-kappa-B-alpha	0.024	0.031	-10000	0	-0.37	3	3
FADD	-0.012	0.13	-10000	0	-0.44	19	19
KSR1	0.012	0.045	-10000	0	-0.19	8	8
MAPK8	-0.004	0.087	-10000	0	-0.22	56	56
TRAF2	0.014	0.042	-10000	0	-0.46	4	4
response to radiation	0	0	-10000	0	-0.002	1	1
CHUK	-0.006	0.13	-10000	0	-0.44	19	19
TNF R/SODD	0.014	0.055	-10000	0	-0.37	5	5
TNF	-0.004	0.094	-10000	0	-0.36	31	31
CYCS	0.036	0.056	0.14	64	-0.17	5	69
IKBKG	0	0.12	-10000	0	-0.47	12	12
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.012	0.13	-10000	0	-0.39	25	25
RELA	0.018	0	-10000	0	-10000	0	0
RIPK1	0.017	0.023	-10000	0	-0.52	1	1
AIFM1	0.036	0.056	0.14	63	-0.17	5	68
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	0.033	-10000	0	-10000	0	0
NSMAF	-0.008	0.13	-10000	0	-0.46	15	15
response to hydrogen peroxide	0	0	-10000	0	-0.002	4	4
BCL2	-0.12	0.22	-10000	0	-0.47	145	145

×

VEGFR1 specific signals

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	-0.008	0.14	-9999	-0.38	55	55
VEGFR1 homodimer/NRP1	-0.02	0.14	-9999	-0.38	55	55
mol:DAG	-0.003	0.13	-9999	-0.61	13	13
VEGFR1 homodimer/NRP1/VEGFR 121	-0.016	0.14	-9999	-0.35	58	58
CaM/Ca2+	0.007	0.13	-9999	-0.63	11	11
HIF1A	-0.034	0.17	-9999	-0.47	66	66
GAB1	0.006	0.074	-9999	-0.43	14	14
AKT1	0.001	0.14	-9999	-0.54	18	18
PLCG1	-0.003	0.13	-9999	-0.62	13	13
NOS3	0.019	0.12	-9999	-0.58	11	11
CBL	0.017	0.012	-9999	-0.26	1	1
mol:NO	0.02	0.12	-9999	-0.53	12	12
FLT1	-0.019	0.16	-9999	-0.45	55	55
PGF	0.012	0.051	-9999	-0.41	7	7
VEGFR1 homodimer/NRP2/VEGFR121	-0.009	0.14	-9999	-0.65	14	14
CALM1	0.018	0	-9999	-10000	0	0
PIK3CA	0.016	0.029	-9999	-0.35	3	3
eNOS/Hsp90	0.027	0.12	-9999	-0.54	11	11
endothelial cell proliferation	0.002	0.13	-9999	-0.6	13	13
mol:Ca2+	-0.003	0.13	-9999	-0.61	13	13
MAPK3	0.008	0.12	-9999	-0.57	12	12
MAPK1	0.008	0.12	-9999	-0.58	11	11
PIK3R1	-0.009	0.11	-9999	-0.42	32	32
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	0.081	-9999	-0.32	28	28
VEGFA homodimer	0	0.076	-9999	-0.29	31	31
VEGFR1 homodimer/VEGFA homodimer	-0.018	0.15	-9999	-0.38	58	58
platelet activating factor biosynthetic process	0.013	0.12	-9999	-0.55	12	12
PI3K	-0.003	0.14	-9999	-0.59	16	16
PRKCA	0.002	0.12	-9999	-0.62	11	11
PRKCB	-0.004	0.12	-9999	-0.57	13	13
VEGFR1 homodimer/PLGF homodimer	-0.011	0.14	-9999	-0.38	58	58
VEGFA	0	0.076	-9999	-0.29	31	31
VEGFB	0.017	0.023	-9999	-0.52	1	1
mol:IP3	-0.003	0.13	-9999	-0.61	13	13
RASA1	-0.007	0.14	-9999	-0.63	14	14
NRP2	0.01	0.052	-9999	-0.33	11	11
VEGFR1 homodimer	-0.019	0.16	-9999	-0.44	55	55
VEGFB homodimer	0.017	0.023	-9999	-0.52	1	1
NCK1	0.011	0.046	-9999	-0.28	12	12
eNOS/Caveolin-1	0.021	0.13	-9999	-0.58	12	12
PTPN11	0.017	0.023	-9999	-0.52	1	1
mol:PI-3-4-5-P3	-0.004	0.14	-9999	-0.58	16	16
mol:L-citrulline	0.02	0.12	-9999	-0.53	12	12
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.005	0.13	-9999	-0.62	12	12
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.008	0.14	-9999	-0.65	13	13
CD2AP	0.016	0.029	-9999	-0.35	3	3
PI3K/GAB1	0	0.14	-9999	-0.56	16	16
PDPK1	-0.002	0.13	-9999	-0.56	15	15
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.006	0.14	-9999	-0.63	13	13
mol:NADP	0.02	0.12	-9999	-0.53	12	12
HSP90AA1	0.013	0.045	-9999	-0.39	6	6
ubiquitin-dependent protein catabolic process	0.004	0.13	-9999	-0.62	12	12
VEGFR1 homodimer/NRP2	-0.012	0.15	-9999	-0.38	56	56

×

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	0.15	-9999	-0.46	30	30
PDGFB-D/PDGFRB/SLAP	0.01	0.074	-9999	-0.37	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	-0.5	21	21
PIK3CA	0.016	0.029	-9999	-0.35	3	3
FGR	-0.008	0.065	-9999	-0.39	10	10
mol:Ca2+	0.003	0.11	-9999	-0.62	11	11
MYC	-0.029	0.22	-9999	-0.74	42	42
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	0.098	-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	-0.26	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	-0.34	52	52
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	-0.018	0.15	-9999	-0.46	34	34
positive regulation of MAPKKK cascade	0.019	0.052	-9999	-0.37	9	9
PIK3R1	-0.009	0.11	-9999	-0.42	32	32
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	0.086	-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	-0.26	1	1
VAV2	-0.011	0.14	-9999	-0.59	17	17
CBL	0.017	0.012	-9999	-0.26	1	1
PDGFB-D/PDGFRB/DEP1	0.015	0.063	-9999	-0.37	13	13
LCK	-0.081	0.2	-9999	-0.56	68	68
PDGFRB	0.009	0.067	-9999	-0.53	8	8
ACP1	0.013	0.052	-9999	-0.52	5	5
HCK	-0.03	0.14	-9999	-0.55	28	28
ABL1	-0.005	0.11	-9999	-0.5	16	16
PDGFB-D/PDGFRB/CBL	-0.01	0.14	-9999	-0.66	15	15
PTPN1	0.001	0.071	-9999	-0.29	28	28
SNX15	0.017	0.012	-9999	-0.26	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	-0.64	43	43
SLA	0.004	0.078	-9999	-0.39	18	18
actin cytoskeleton reorganization	0.032	0.07	-9999	-0.37	7	7
SRC	-0.01	0.084	-9999	-0.46	12	12
PI3K	-0.065	0.12	-9999	-0.44	31	31
PDGFB-D/PDGFRB/GRB7/SHC	0.009	0.075	-9999	-0.31	17	17
SH2B2	0	0	-9999	-10000	0	0
PLCgamma1/SPHK1	-0.007	0.14	-9999	-0.53	21	21
LYN	-0.008	0.066	-9999	-0.4	10	10
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	0.063	-9999	-0.32	7	7
SPHK1	-0.027	0.14	-9999	-0.42	54	54
EDG1	-0.021	0.13	-9999	-0.41	48	48
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	90	90
YES1	-0.016	0.096	-9999	-0.47	18	18
cell migration	-0.038	0.15	-9999	-0.35	90	90
SHC/Grb2/SOS1	0.036	0.06	-9999	-0.35	4	4
SLC9A3R2	-0.032	0.15	-9999	-0.49	52	52
SLC9A3R1	-0.044	0.16	-9999	-0.44	71	71
NHERF1-2/PDGFRB/PTEN	-0.033	0.16	-9999	-0.32	102	102
FYN	-0.016	0.13	-9999	-0.78	11	11
DOK1	0.013	0.074	-9999	-0.3	23	23
HRAS/GTP	0.009	0.037	-9999	-0.29	7	7
PDGFB	0.008	0.064	-9999	-0.39	12	12
RAC1	-0.012	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	-0.007	0.051	-9999	-0.34	4	4
RASA1	0.013	0.072	-9999	-0.29	22	22
NCK1	0.011	0.046	-9999	-0.28	12	12
NCK2	0.015	0.027	-9999	-0.26	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	-0.48	16	16
STAT1-3-5/STAT1-3-5	-0.022	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	-0.45	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	-0.059	0.17	-9999	-0.4	98	98
LRPAP1	0.016	0.026	-9999	-0.39	2	2
NUDC	0.018	0	-9999	-10000	0	0
RELN/LRP8	-0.014	0.1	-9999	-0.31	42	42
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	0.092	-9999	-0.28	42	42
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	36	36
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.015	0.037	-9999	-0.39	4	4
CDK5R1	0.014	0.031	-9999	-0.26	7	7
LIS1/Poliovirus Protein 3A	0.018	0.02	-9999	-0.31	2	2
CDK5R2	0.017	0.017	-9999	-0.26	2	2
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.016	0.11	-9999	-0.31	57	57
YWHAE	0.016	0.029	-9999	-0.35	3	3
NDEL1/14-3-3 E	0.025	0.079	-9999	-0.29	4	4
MAP1B	-0.014	0.073	-9999	-0.29	32	32
RAC1	0.024	0.01	-9999	-10000	0	0
p35/CDK5	0.007	0.085	-9999	-0.31	4	4
RELN	0.009	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	0.003	0.095	-9999	-0.45	3	3
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	-0.26	1	1
MAP1B/LIS1/Dynein heavy chain	0.014	0.054	-9999	-0.31	2	2
NDEL1/Katanin 60/Dynein heavy chain	0.031	0.078	-9999	-0.27	3	3
LRP8	-0.057	0.16	-9999	-0.34	109	109
NDEL1/Katanin 60	0.024	0.079	-9999	-0.29	3	3
P39/CDK5	0.009	0.084	-9999	-0.23	42	42
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	42	42
PPP2R5D	0.016	0.021	-9999	-0.26	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	0.004	0.1	-9999	-0.25	57	57
RELN/VLDLR	-0.043	0.13	-9999	-0.28	111	111
CDC42	0.024	0.01	-9999	-10000	0	0

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.015	0.035	-10000	0	-0.32	4	4
RAS family/GTP	0.002	0.098	-10000	0	-0.31	25	25
NFATC4	0.008	0.079	0.2	1	-0.32	11	12
ERBB2IP	0.016	0.033	-10000	0	-0.52	2	2
HSP90 (dimer)	0.013	0.045	-10000	0	-0.39	6	6
mammary gland morphogenesis	-0.009	0.094	0.23	1	-0.31	22	23
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	0.22	1	-0.39	10	11
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.012	0.1	0.24	1	-0.3	47	48
AKT1	0.008	0.038	-10000	0	-0.26	9	9
BAD	0.016	0.035	-10000	0	-0.31	5	5
MAPK10	0.002	0.069	-10000	0	-0.22	19	19
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.009	0.1	0.25	1	-0.34	22	23
RAF1	0.007	0.1	-10000	0	-0.33	19	19
ErbB2/ErbB3/neuregulin 2	-0.037	0.12	0.24	1	-0.34	56	57
STAT3	0.016	0.095	-10000	0	-0.95	5	5
cell migration	0.009	0.07	0.18	1	-0.21	16	17
mol:PI-3-4-5-P3	0	0.002	-10000	0	-10000	0	0
cell proliferation	-0.045	0.24	-10000	0	-0.62	54	54
FOS	-0.06	0.22	-10000	0	-0.45	105	105
NRAS	0.006	0.073	-10000	0	-0.4	15	15
mol:Ca2+	-0.009	0.094	0.23	1	-0.31	22	23
MAPK3	-0.021	0.19	-10000	0	-0.47	51	51
MAPK1	-0.021	0.19	-10000	0	-0.47	53	53
JAK2	-0.003	0.096	0.22	1	-0.38	14	15
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	38	38
NRG1	0.008	0.049	-10000	0	-0.26	17	17
GRB2/SOS1	0.024	0.024	-10000	0	-0.37	1	1
MAPK8	0	0.089	0.22	1	-0.26	39	40
MAPK9	0.008	0.067	-10000	0	-0.22	17	17
ERBB2	-0.03	0.085	0.38	1	-0.34	20	21
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	0.021	0.031	-10000	0	-0.28	4	4
FRAP1	0.016	0.032	-10000	0	-0.31	4	4
RAC1-CDC42/GTP	-0.022	0.054	-10000	0	-0.27	10	10
ErbB2/ErbB2/HSP90 (dimer)	-0.014	0.076	0.26	1	-0.32	18	19
CHRNA1	-0.008	0.16	-10000	0	-0.43	36	36
myelination	0.014	0.079	0.21	1	-0.32	11	12
PPP3CB	0	0.086	0.21	1	-0.37	9	10
KRAS	0.008	0.069	-10000	0	-0.45	11	11
RAC1-CDC42/GDP	0.021	0.074	-10000	0	-0.29	10	10
NRG2	-0.016	0.1	-10000	0	-0.3	57	57
mol:GDP	0.001	0.082	-10000	0	-0.27	38	38
SOS1	0.017	0.023	-10000	0	-0.52	1	1
MAP2K2	0.007	0.11	-10000	0	-0.35	20	20
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	0.22	1	-0.4	9	10
MAP2K1	-0.024	0.17	-10000	0	-0.45	33	33
heart morphogenesis	-0.009	0.094	0.23	1	-0.31	22	23
RAS family/GDP	0.013	0.097	-10000	0	-0.32	20	20
GRB2	0.015	0.024	-10000	0	-0.26	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	-0.009	0.094	0.23	1	-0.31	22	23
CDC42	0.018	0	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.019	0.091	-9999	-0.3	34	34
MAP4K1	0.011	0.041	-9999	-0.26	12	12
MAP3K8	-0.036	0.15	-9999	-0.39	69	69
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	0.005	0.1	-9999	-0.35	12	12
JUN	-0.008	0.092	-9999	-0.33	20	20
MAP3K7	0.029	0.067	-9999	-0.28	6	6
GRAP2	0.011	0.044	-9999	-0.28	11	11
CRK	0.016	0.033	-9999	-0.52	2	2
MAP2K4	0.005	0.096	-9999	-0.35	16	16
LAT	0.002	0.069	-9999	-0.28	29	29
LCP2	-0.005	0.1	-9999	-0.41	28	28
MAPK8	0.011	0.052	-9999	-0.58	3	3
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.024	0.07	-9999	-0.3	6	6
LAT/GRAP2/SLP76/HPK1/HIP-55	0.025	0.089	-9999	-0.28	37	37

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.016	0.023	-9999	-0.52	1	1
HDAC2	0.009	0.054	-9999	-0.29	15	15
GNB1/GNG2	-0.007	0.11	-9999	-0.31	53	53
forebrain development	0.007	0.13	-9999	-0.53	17	17
GNAO1	0.017	0.024	-9999	-0.26	4	4
SMO/beta Arrestin2	-0.017	0.12	-9999	-0.37	47	47
SMO	-0.046	0.16	-9999	-0.41	80	80
ARRB2	0.019	0.001	-9999	-10000	0	0
GLI3/SPOP	0.01	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	-0.014	0.12	-9999	-0.38	44	44
XPO1	0.021	0.003	-9999	-10000	0	0
GLI1/Su(fu)	-0.003	0.16	-9999	-0.56	25	25
SAP30	0.012	0.053	-9999	-0.48	6	6
mol:GDP	-0.045	0.16	-9999	-0.41	80	80
MIM/GLI2A	-0.023	0.14	-9999	-0.4	61	61
IFT88	-0.001	0.097	-9999	-0.48	20	20
GNAI3	0.018	0.023	-9999	-0.52	1	1
GLI2	0.036	0.054	-9999	-0.41	1	1
GLI3	0.003	0.14	-9999	-0.39	28	28
CSNK1D	0.018	0	-9999	-10000	0	0
CSNK1E	0.017	0.012	-9999	-0.26	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	-0.35	3	3
Gi family/GTP	-0.007	0.11	-9999	-0.39	23	23
SIN3B	0.017	0.012	-9999	-0.26	1	1
SIN3A	0.017	0	-9999	-10000	0	0
GLI3/Su(fu)	0.009	0.14	-9999	-0.46	30	30
GLI2/Su(fu)	0.027	0.099	-9999	-0.45	6	6
FOXA2	-0.051	0.18	-9999	-0.73	34	34
neural tube patterning	0.007	0.13	-9999	-0.53	17	17
SPOP	0.013	0.042	-9999	-0.33	7	7
Su(fu)/PIAS1	0.005	0.092	-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	0.007	0.13	-9999	-0.53	17	17
SUFU	-0.005	0.1	-9999	-0.38	21	21
LGALS3	-0.041	0.16	-9999	-0.48	63	63
catabolic process	0.031	0.12	-9999	-0.41	14	14
GLI3A/CBP	0.007	0.069	-9999	-0.37	9	9
KIF3A	0.005	0.081	-9999	-0.5	13	13
GLI1	0.007	0.13	-9999	-0.54	17	17
RAB23	0.009	0.061	-9999	-0.37	12	12
CSNK1A1	0.017	0.023	-9999	-0.52	1	1
IFT172	0.013	0.05	-9999	-0.43	6	6
RBBP7	0.01	0.051	-9999	-0.3	13	13
Su(fu)/Galectin3	-0.027	0.14	-9999	-0.34	71	71
GNAZ	0.003	0.085	-9999	-0.43	18	18
RBBP4	0.016	0.026	-9999	-0.39	2	2
CSNK1G1	0.017	0.012	-9999	-0.26	1	1
PIAS1	0.017	0.012	-9999	-0.26	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	0.001	0.11	-9999	-0.4	20	20
PTCH1	0.016	0.12	-9999	-0.6	8	8
MIM/GLI1	0.002	0.16	-9999	-0.5	24	24
CREBBP	0.007	0.069	-9999	-0.37	9	9
Su(fu)/SIN3/HDAC complex	0.036	0.047	-9999	-0.26	1	1

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.011	0.056	-10000	0	-0.31	12	12
cell-cell adhesion	0.036	0.083	0.37	18	-10000	0	18
Ephrin B/EPHB2/RasGAP	0.024	0.086	-10000	0	-0.28	30	30
ITSN1	0.015	0.035	-10000	0	-0.43	3	3
PIK3CA	0.016	0.029	-10000	0	-0.35	3	3
SHC1	0.017	0.023	-10000	0	-0.52	1	1
Ephrin B1/EPHB3	0.005	0.072	-10000	0	-0.32	21	21
Ephrin B1/EPHB1	-0.004	0.071	-10000	0	-0.31	13	13
HRAS/GDP	-0.033	0.079	-10000	0	-0.31	26	26
Ephrin B/EPHB1/GRB7	-0.002	0.096	-10000	0	-0.27	32	32
Endophilin/SYNJ1	0.019	0.063	-10000	0	-0.23	23	23
KRAS	0.008	0.069	-10000	0	-0.45	11	11
Ephrin B/EPHB1/Src	0.014	0.088	-10000	0	-0.28	24	24
endothelial cell migration	-0.003	0.1	-10000	0	-0.28	55	55
GRB2	0.016	0.024	-10000	0	-0.26	4	4
GRB7	-0.017	0.1	-10000	0	-0.29	59	59
PAK1	0.003	0.092	-10000	0	-0.35	8	8
HRAS	0.012	0.051	-10000	0	-0.41	7	7
RRAS	0.016	0.074	-10000	0	-0.25	30	30
DNM1	0.012	0.052	-10000	0	-0.39	8	8
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.006	0.078	-10000	0	-0.26	25	25
lamellipodium assembly	-0.036	0.083	-10000	0	-0.37	18	18
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.016	0.076	-10000	0	-0.47	5	5
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
EPHB2	0.007	0.062	-10000	0	-0.32	16	16
EPHB3	-0.005	0.1	-10000	0	-0.45	26	26
EPHB1	-0.023	0.11	-10000	0	-0.28	73	73
EPHB4	-0.01	0.11	-10000	0	-0.42	33	33
mol:GDP	0.003	0.098	-10000	0	-0.33	23	23
Ephrin B/EPHB2	0.02	0.069	-10000	0	-0.25	24	24
Ephrin B/EPHB3	0.013	0.085	-10000	0	-0.27	36	36
JNK cascade	0.007	0.081	-10000	0	-0.28	21	21
Ephrin B/EPHB1	0.005	0.083	-10000	0	-0.26	31	31
RAP1/GDP	0.014	0.097	-10000	0	-0.33	15	15
EFNB2	-0.006	0.1	-10000	0	-0.39	31	31
EFNB3	0.018	0	-10000	0	-10000	0	0
EFNB1	0.01	0.051	-10000	0	-0.3	13	13
Ephrin B2/EPHB1-2	-0.006	0.088	-10000	0	-0.28	32	32
RAP1B	0.013	0.044	-10000	0	-0.32	8	8
RAP1A	0.011	0.062	-10000	0	-0.52	7	7
CDC42/GTP	-0.03	0.075	-10000	0	-0.39	11	11
Rap1/GTP	-0.031	0.079	-10000	0	-0.4	14	14
axon guidance	0.011	0.056	-10000	0	-0.3	12	12
MAPK3	0.028	0.069	-10000	0	-0.42	5	5
MAPK1	0.027	0.07	-10000	0	-0.39	6	6
Rac1/GDP	0.013	0.093	-10000	0	-0.31	21	21
actin cytoskeleton reorganization	-0.034	0.073	-10000	0	-0.31	18	18
CDC42/GDP	0.013	0.093	-10000	0	-0.31	21	21
PI3K	0	0.1	-10000	0	-0.28	55	55
EFNA5	0.006	0.069	-10000	0	-0.35	17	17
Ephrin B2/EPHB4	-0.007	0.096	-10000	0	-0.34	35	35
Ephrin B/EPHB2/Intersectin/N-WASP	0.021	0.068	-10000	0	-0.3	3	3
CDC42	0.018	0	-10000	0	-10000	0	0
RAS family/GTP	-0.034	0.076	-10000	0	-0.34	17	17
PTK2	0.007	0.034	-10000	0	-0.34	3	3
MAP4K4	0.007	0.082	-10000	0	-0.28	21	21
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	0.011	0.11	-10000	0	-0.34	21	21
MAP2K1	0.022	0.072	-10000	0	-0.44	5	5
WASL	0.01	0.066	-10000	0	-0.52	8	8
Ephrin B1/EPHB1-2/NCK1	0.011	0.082	-10000	0	-0.27	26	26
cell migration	0.027	0.076	-10000	0	-0.45	5	5
NRAS	0.006	0.072	-10000	0	-0.4	15	15
SYNJ1	0.02	0.064	-10000	0	-0.24	23	23
PXN	0.018	0	-10000	0	-10000	0	0
TF	0.02	0.065	-10000	0	-0.32	1	1
HRAS/GTP	0.004	0.092	-10000	0	-0.38	12	12
Ephrin B1/EPHB1-2	0.003	0.075	-10000	0	-0.27	22	22
cell adhesion mediated by integrin	0.012	0.061	0.26	20	-10000	0	20
RAC1	0.018	0	-10000	0	-10000	0	0
mol:GTP	0.008	0.097	-10000	0	-0.41	11	11
RAC1-CDC42/GTP	-0.034	0.08	-10000	0	-0.35	18	18
RASA1	0.004	0.079	-10000	0	-0.42	16	16
RAC1-CDC42/GDP	0.02	0.09	-10000	0	-0.34	9	9
ruffle organization	0.01	0.1	-10000	0	-0.38	17	17
NCK1	0.011	0.046	-10000	0	-0.28	12	12
receptor internalization	0.022	0.067	-10000	0	-0.33	2	2
Ephrin B/EPHB2/KALRN	0.025	0.077	-10000	0	-0.27	22	22
ROCK1	0.012	0.064	-10000	0	-0.28	21	21
RAS family/GDP	-0.034	0.075	-10000	0	-0.32	18	18
Rac1/GTP	-0.038	0.088	-10000	0	-0.39	18	18
Ephrin B/EPHB1/Src/Paxillin	0.014	0.076	-10000	0	-0.27	24	24

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.012	0.11	-9999	-0.4	37	37
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	-0.005	0.099	-9999	-0.39	30	30
RAC1-CDC42/GTP/PAK family	-0.001	0.071	-9999	-0.22	40	40
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	-0.26	1	1
FYN	0.009	0.063	-9999	-0.4	11	11
MAP3K12	0.018	0	-9999	-10000	0	0
FGR	0.017	0.017	-9999	-0.26	2	2
p38 alpha/TAB1	0.011	0.093	-9999	-0.28	28	28
PRKG1	0.017	0.012	-9999	-0.26	1	1
DUSP8	-0.005	0.11	-9999	-0.47	25	25
PGK/cGMP/p38 alpha	-0.028	0.07	-9999	-0.27	28	28
apoptosis	0.01	0.089	-9999	-0.27	28	28
RAL/GTP	0.022	0.029	-9999	-0.31	4	4
LYN	0.014	0.031	-9999	-0.26	7	7
DUSP1	-0.038	0.15	-9999	-0.41	69	69
PAK1	-0.022	0.13	-9999	-0.38	53	53
SRC	0.015	0.035	-9999	-0.43	3	3
RAC1/OSM/MEKK3/MKK3	0.043	0.022	-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	0.003	0.11	-9999	-0.32	33	33
BLK	-0.018	0.1	-9999	-0.29	61	61
HCK	-0.005	0.11	-9999	-0.47	25	25
MAP2K3	0.014	0.037	-9999	-0.3	7	7
DUSP16	0.005	0.078	-9999	-0.43	15	15
DUSP10	-0.017	0.12	-9999	-0.4	44	44
TRAF6/MEKK3	0.022	0.015	-9999	-0.28	1	1
MAP3K7IP1	0.018	0	-9999	-10000	0	0
MAPK14	0.004	0.099	-9999	-0.3	32	32
positive regulation of innate immune response	0.003	0.12	-9999	-0.37	30	30
LCK	-0.073	0.18	-9999	-0.4	115	115
p38alpha-beta/MKP7	0.006	0.13	-9999	-0.36	34	34
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	-0.012	0.14	-9999	-0.36	43	43
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

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	0.015	0.029	-9999	-0.26	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	0.026	-9999	-0.24	1	1
FIH (dimer)	0.017	0.023	-9999	-0.52	1	1
CDKN2A	-0.054	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	18	18
CUL2	0.017	0.017	-9999	-0.26	2	2
OS9	0.014	0.041	-9999	-0.35	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	-0.32	20	20
PHD1-3/OS9	-0.021	0.12	-9999	-0.28	80	80
HIF1A/RACK1/Elongin B/Elongin C	0.012	0.083	-9999	-0.34	5	5
VHL	0.014	0.031	-9999	-0.26	7	7
HSP90AA1	0.013	0.045	-9999	-0.39	6	6
HIF1A/JAB1	-0.004	0.087	-9999	-0.3	20	20
EGLN3	-0.074	0.18	-9999	-0.4	116	116
EGLN2	0.011	0.054	-9999	-0.38	9	9
EGLN1	0.001	0.082	-9999	-0.36	23	23
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	0.021	-9999	-0.26	3	3
RBX1	0.018	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.032	0.11	-9999	-0.33	33	33

×

Signaling events mediated by PRL

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
CCNE1	-0.018	0.1	-10000	0	-0.28	64	64
mol:Halofuginone	0.004	0.012	-10000	0	-10000	0	0
ITGA1	0.001	0.093	-10000	0	-0.51	17	17
CDKN1A	-0.017	0.12	-10000	0	-0.46	24	24
PRL-3/alpha Tubulin	0.023	0.026	-10000	0	-0.37	1	1
mol:Ca2+	-0.078	0.14	0.38	1	-0.38	65	66
AGT	-0.097	0.19	-10000	0	-0.37	159	159
CCNA2	-0.042	0.13	-10000	0	-0.42	20	20
TUBA1B	0.018	0	-10000	0	-10000	0	0
EGR1	-0.06	0.15	-10000	0	-0.37	81	81
CDK2/Cyclin E1	-0.016	0.12	-10000	0	-0.44	27	27
MAPK3	0.022	0.032	-10000	0	-0.37	2	2
PRL-2 /Rab GGTase beta	0.017	0.056	-10000	0	-0.37	9	9
MAPK1	0.021	0.036	-10000	0	-0.37	3	3
PTP4A1	-0.031	0.12	-10000	0	-0.6	5	5
PTP4A3	0.014	0.037	-10000	0	-0.3	7	7
PTP4A2	0.005	0.075	-10000	0	-0.42	15	15
ITGB1	0.02	0.037	-10000	0	-0.37	3	3
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	0.012	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.022	0.12	-10000	0	-0.52	6	6
RABGGTA	0.018	0	-10000	0	-10000	0	0
BCAR1	0.002	0.023	0.38	1	-10000	0	1
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	-0.55	5	5
PRL-3/alpha1 Integrin	0.011	0.075	-10000	0	-0.39	16	16
ROCK1	0.002	0.075	-10000	0	-0.36	6	6
RABGGTB	0.017	0.017	-10000	0	-0.26	2	2
CDK2	0.011	0.047	-10000	0	-0.31	10	10
mitosis	-0.03	0.12	-10000	0	-0.59	5	5
ATF5	0.013	0.041	-10000	0	-0.29	9	9

×

p38 MAPK signaling 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
TRAF6/ASK1	0.002	0.073	-9999	-0.26	33	33
TRAF2/ASK1	-0.002	0.084	-9999	-0.31	32	32
ATM	0.017	0.012	-9999	-0.26	1	1
MAP2K3	-0.012	0.12	-9999	-0.37	39	39
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.016	0.12	-9999	-0.32	45	45
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.003	0.083	-9999	-0.46	16	16
TXN	0.01	0.008	-9999	-10000	0	0
CALM1	0.018	0	-9999	-10000	0	0
GADD45A	-0.012	0.11	-9999	-0.39	38	38
GADD45B	-0.002	0.097	-9999	-0.44	23	23
MAP3K1	-0.031	0.14	-9999	-0.43	58	58
MAP3K6	0.015	0.035	-9999	-0.43	3	3
MAP3K7	0.016	0.021	-9999	-0.26	3	3
MAP3K4	0.018	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	-0.003	0.098	-9999	-0.37	32	32
TAK1/TAB family	0.01	0.039	-9999	-0.42	4	4
RAC1/OSM/MEKK3	0.034	0.006	-9999	-10000	0	0
TRAF2	0.014	0.042	-9999	-0.46	4	4
RAC1/OSM/MEKK3/MKK3	-0.03	0.079	-9999	-0.33	18	18
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	-0.079	0.18	-9999	-0.37	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	86	86
OSM/MEKK3	0.026	0.008	-9999	-10000	0	0
TAOK1	0.013	0.041	-9999	-0.32	6	6
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	-0.26	1	1
MAP3K7IP2	0.014	0.047	-9999	-0.52	4	4
MAP3K5	-0.021	0.13	-9999	-0.42	46	46
MAP3K10	-0.001	0.097	-9999	-0.48	20	20
MAP3K3	0.017	0.012	-9999	-0.26	1	1
TRX/ASK1	-0.003	0.078	-9999	-0.31	29	29
GADD45/MTK1/MTK1	0.009	0.097	-9999	-0.29	42	42

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.021	0.042	-10000	0	-0.37	5	5
ATM	0.017	0.012	-10000	0	-0.26	1	1
UBE2D3	0.018	0	-10000	0	-10000	0	0
PRKDC	0.012	0.046	-10000	0	-0.32	9	9
ATR	0.017	0.012	-10000	0	-0.26	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	-0.26	1	1
M/R/N Complex	0.029	0.047	-10000	0	-0.3	10	10
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	-0.37	6	6
FANCF	0.012	0.057	-10000	0	-0.52	6	6
BRCA1	0	0.094	-10000	0	-0.48	19	19
CCNE1	-0.018	0.1	-10000	0	-0.28	64	64
CDK2/Cyclin E1	-0.002	0.081	-10000	0	-0.38	11	11
FANCG	0.016	0.024	-10000	0	-0.26	4	4
BRCA1/BACH1/BARD1	0.01	0.076	-10000	0	-0.37	20	20
FANCE	0.006	0.062	-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	0.13	-10000	0	-0.31	80	80
DNA repair	0.013	0.12	-10000	0	-0.39	22	22
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	-0.26	7	7
mRNA polyadenylation	-0.021	0.042	0.37	5	-10000	0	5
BRCA1/BARD1/CTIP/M/R/N Complex	0.026	0.058	-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	0.059	-10000	0	-0.38	11	11
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	-0.004	0.12	-10000	0	-0.28	73	73
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	0.074	-10000	0	-0.34	6	6
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	-0.26	2	2
G1/S transition of mitotic cell cycle	-0.008	0.11	0.3	51	-10000	0	51
BRCA1/BARD1	0.019	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	0.011	0.047	-10000	0	-0.31	10	10
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.039	0.16	-10000	0	-0.47	62	62
RAD50	0.01	0.066	-10000	0	-0.52	8	8
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

×

Signaling events mediated by HDAC Class III

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
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	0.026	0.24	3	-10000	0	3
CDKN1A	-0.016	0.12	-10000	0	-0.71	15	15
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.016	0.021	-10000	0	-0.26	3	3
FOXO3	0.001	0.043	0.41	4	-0.25	4	8
FOXO1	0.001	0.089	-10000	0	-0.46	18	18
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	-0.26	1	1
TAT	-0.007	0.079	-10000	0	-0.26	48	48
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.012	0.091	-10000	0	-0.33	37	37
PPARGC1A	-0.012	0.1	-10000	0	-0.31	48	48
FHL2	-0.08	0.19	-10000	0	-0.41	120	120
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	0.026	-10000	0	-0.24	3	3
SIRT1/FOXO3a	0.005	0.041	0.32	4	-0.2	5	9
SIRT1	0.015	0.039	0.2	9	-0.35	3	12
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	37	37
apoptosis	-0.033	0.028	0.3	1	-10000	0	1
SIRT1/PGC1A	0.005	0.064	-10000	0	-0.31	11	11
p53/SIRT1	-0.017	0.11	0.4	9	-0.37	32	41
SIRT1/FOXO4	0.026	0.037	-10000	0	-0.24	7	7
FOXO1/FHL2/SIRT1	-0.031	0.12	-10000	0	-0.3	81	81
HIST1H1E	-0.005	0.08	-10000	0	-0.27	39	39
SIRT1/p300	0.021	0.043	-10000	0	-0.36	5	5
muscle cell differentiation	0.002	0.081	0.31	30	-10000	0	30
TP53	-0.023	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	-0.31	30	30

×

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	0.02	0.062	-10000	0	-0.32	4	4
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.017	0.012	-10000	0	-0.26	1	1
AKT1	0.029	0.093	0.22	53	-0.24	21	74
RAR alpha/9cRA/Cyclin H	-0.024	0.063	-10000	0	-0.4	5	5
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.014	0.071	-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	0.014	0.052	-10000	0	-0.36	6	6
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	0.012	0.052	-10000	0	-0.39	8	8
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	-0.46	10	10
RARA	0.017	0.052	-10000	0	-0.26	11	11
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.013	0.068	-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	0.065	-10000	0	-0.32	13	13
RXRA	0.011	0.08	-10000	0	-0.33	5	5
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	-0.054	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	-0.26	1	1
RAR alpha/RXRs	0.02	0.15	-10000	0	-0.42	19	19
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.022	0.11	-10000	0	-0.37	8	8
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.068	-10000	0	-0.29	6	6
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.026	0.21	-10000	0	-0.6	54	54
positive regulation of DNA binding	-0.023	0.06	-10000	0	-0.38	5	5
NRIP1	-0.086	0.38	-10000	0	-1.2	53	53
RXRs/RARs	-0.012	0.15	-10000	0	-0.42	55	55
RXRs/RXRs/DNA/9cRA	0.003	0.12	-10000	0	-0.41	8	8
PRKACA	0.018	0	-10000	0	-10000	0	0
CDK7	0.017	0.012	-10000	0	-0.26	1	1
TFIIH	0.033	0.031	-10000	0	-0.3	4	4
RAR alpha/9cRA	0.039	0.044	-10000	0	-0.26	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	-0.003	0.022	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0	0.095	-9999	-0.4	23	23
AKT1	0.03	0.15	-9999	-0.5	22	22
PTK2B	0.015	0.13	-9999	-0.59	14	14
VEGFR2 homodimer/Frs2	0.021	0.095	-9999	-0.48	14	14
CAV1	0	0.081	-9999	-0.32	28	28
CALM1	0.018	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.02	0.11	-9999	-0.57	10	10
endothelial cell proliferation	0.046	0.13	-9999	-0.46	18	18
mol:Ca2+	0.014	0.14	-9999	-0.57	17	17
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.033	0.1	-9999	-0.55	9	9
RP11-342D11.1	0.004	0.14	-9999	-0.58	16	16
CDH5	0.013	0.052	-9999	-0.52	5	5
VEGFA homodimer	0.003	0.1	-9999	-0.27	52	52
SHC1	0.017	0.023	-9999	-0.52	1	1
SHC2	-0.061	0.19	-9999	-0.51	78	78
HRAS/GDP	-0.036	0.099	-9999	-0.51	15	15
SH2D2A	-0.038	0.15	-9999	-0.38	75	75
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.044	0.12	-9999	-0.46	16	16
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.007	0.13	-9999	-0.53	14	14
VEGFR1 homodimer	0.005	0.077	-9999	-0.44	14	14
SHC/GRB2/SOS1	0.025	0.13	-9999	-0.56	15	15
GRB10	0.004	0.17	-9999	-0.6	29	29
PTPN11	0.017	0.023	-9999	-0.52	1	1
GRB2	0.016	0.024	-9999	-0.26	4	4
PAK1	-0.022	0.13	-9999	-0.38	53	53
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.029	0.12	-9999	-0.53	14	14
HRAS	0.012	0.051	-9999	-0.41	7	7
VEGF/Rho/ROCK1/Integrin Complex	0.017	0.12	-9999	-0.54	15	15
HIF1A	-0.037	0.16	-9999	-0.46	61	61
FRS2	0.01	0.047	-9999	-0.28	13	13
oxygen and reactive oxygen species metabolic process	0.032	0.1	-9999	-0.55	9	9
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	0.019	0.12	-9999	-0.62	10	10
mol:GDP	-0.038	0.1	-9999	-0.53	16	16
mol:NADP	0.042	0.11	-9999	-0.4	16	16
eNOS/Hsp90	0.046	0.11	-9999	-0.41	11	11
PIK3R1	-0.009	0.11	-9999	-0.42	32	32
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	-0.29	31	31
VEGFC	0	0.092	-9999	-0.47	19	19
FAK1/Vinculin	0.035	0.13	-9999	-0.63	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	-0.61	15	15
PTPN6	0.015	0.035	-9999	-0.43	3	3
EPAS1	0.013	0.082	-9999	-0.42	16	16
mol:L-citrulline	0.042	0.11	-9999	-0.4	16	16
ITGAV	-0.003	0.1	-9999	-0.48	22	22
PIK3CA	0.016	0.029	-9999	-0.35	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.029	0.1	-9999	-0.53	10	10
VEGFR2 homodimer/VEGFA homodimer	0.012	0.15	-9999	-0.64	16	16
VEGFR2/3 heterodimer	0.025	0.092	-9999	-0.49	13	13
VEGFB	0.017	0.023	-9999	-0.52	1	1
MAPK11	0.014	0.14	-9999	-0.57	18	18
VEGFR2 homodimer	0.02	0.1	-9999	-0.57	13	13
FLT1	0.005	0.077	-9999	-0.45	14	14
NEDD4	-0.001	0.096	-9999	-0.53	16	16
MAPK3	0.016	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	0.018	0.11	-9999	-0.44	22	22
KDR	0.02	0.1	-9999	-0.57	13	13
VEGFA165/NRP1/VEGFR2 homodimer	0.016	0.15	-9999	-0.57	18	18
SRC	0.015	0.035	-9999	-0.43	3	3
platelet activating factor biosynthetic process	0.017	0.13	-9999	-0.54	17	17
PI3K	0.021	0.16	-9999	-0.57	23	23
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.02	0.11	-9999	-0.59	9	9
FES	0.011	0.15	-9999	-0.62	16	16
GAB1	0.02	0.15	-9999	-0.57	18	18
VEGFR2 homodimer/VEGFA homodimer/Src	0.022	0.11	-9999	-0.59	9	9
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	-0.44	15	15
VEGFR2 homodimer/VEGFA homodimer/Yes	0.018	0.11	-9999	-0.55	12	12
PI3K/GAB1	0.028	0.16	-9999	-0.48	26	26
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.014	0.12	-9999	-0.45	17	17
PRKACA	0.018	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.025	0.11	-9999	-0.52	15	15
HSP90AA1	0.013	0.045	-9999	-0.39	6	6
CDC42	0.014	0.14	-9999	-0.6	16	16
actin cytoskeleton reorganization	-0.007	0.13	-9999	-0.52	14	14
PTK2	0.026	0.14	-9999	-0.65	13	13
EDG1	-0.005	0.19	-9999	-0.65	32	32
mol:DAG	0.014	0.14	-9999	-0.58	17	17
CaM/Ca2+	0.02	0.13	-9999	-0.53	17	17
MAP2K3	0.014	0.14	-9999	-0.55	19	19
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.01	0.18	-9999	-0.61	29	29
PLCG1	0.013	0.14	-9999	-0.59	17	17
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.027	0.11	-9999	-0.48	14	14
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	-0.58	10	10
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.022	0.11	-9999	-0.59	9	9
cell migration	0.055	0.12	-9999	-0.66	8	8
mol:PI-3-4-5-P3	0.022	0.15	-9999	-0.52	23	23
FYN	0.009	0.063	-9999	-0.4	11	11
VEGFB/NRP1	0.013	0.14	-9999	-0.56	16	16
mol:NO	0.042	0.11	-9999	-0.4	16	16
PXN	0.018	0	-9999	-10000	0	0
HRAS/GTP	-0.036	0.099	-9999	-0.51	15	15
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.008	0.17	-9999	-0.61	29	29
VHL	0.014	0.031	-9999	-0.26	7	7
ITGB3	0.002	0.076	-9999	-0.32	25	25
NOS3	0.041	0.12	-9999	-0.45	16	16
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.021	0.15	-9999	-0.48	23	23
RAC1	0.018	0	-9999	-10000	0	0
PRKCA	0.018	0.14	-9999	-0.51	19	19
PRKCB	0.012	0.13	-9999	-0.54	17	17
VCL	0.016	0.029	-9999	-0.35	3	3
VEGFA165/NRP1	0.008	0.14	-9999	-0.59	16	16
VEGFR1/2 heterodimer/VEGFA homodimer	0.017	0.12	-9999	-0.57	13	13
VEGFA165/NRP2	0.009	0.065	-9999	-0.37	8	8
MAPKKK cascade	0.03	0.15	-9999	-0.5	29	29
NRP2	0.01	0.052	-9999	-0.33	11	11
VEGFC homodimer	0	0.092	-9999	-0.46	19	19
NCK1	0.011	0.046	-9999	-0.28	12	12
ROCK1	0.018	0	-9999	-10000	0	0
FAK1/Paxillin	0.035	0.13	-9999	-0.64	11	11
MAP3K13	0.009	0.15	-9999	-0.58	19	19
PDPK1	0.027	0.14	-9999	-0.46	23	23

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	42	42
S1P1/S1P/Gi	0	0.1	-9999	-0.43	15	15
GNAO1	0.016	0.024	-9999	-0.26	4	4
S1P/S1P3/G12/G13	0.02	0.034	-9999	-0.28	5	5
AKT1	0.013	0.097	-9999	-0.58	12	12
AKT3	0.007	0.13	-9999	-1.2	3	3
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	0.017	0.024	-9999	-0.52	1	1
GNAI1	-0.015	0.12	-9999	-0.38	44	44
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.001	0.005	-9999	-0.017	42	42
S1PR2	0	0	-9999	-10000	0	0
EDG1	-0.021	0.13	-9999	-0.41	48	48
mol:Ca2+	0.011	0.082	-9999	-0.4	7	7
MAPK3	0.017	0.078	-9999	-0.4	6	6
MAPK1	0.016	0.079	-9999	-0.4	6	6
JAK2	0.007	0.094	-9999	-0.35	17	17
CXCR4	-0.005	0.11	-9999	-0.42	17	17
FLT1	0.007	0.077	-9999	-0.44	14	14
RhoA/GDP	0.004	0.058	-9999	-0.38	12	12
Rac1/GDP	0.013	0	-9999	-10000	0	0
SRC	0.016	0.081	-9999	-0.39	8	8
S1P/S1P3/Gi	0.011	0.082	-9999	-0.4	7	7
RAC1	0.018	0	-9999	-10000	0	0
RhoA/GTP	0.012	0.087	-9999	-0.41	8	8
VEGFA	0.001	0.077	-9999	-0.29	31	31
S1P/S1P2/Gi	0.01	0.078	-9999	-0.31	13	13
VEGFR1 homodimer/VEGFA homodimer	0.011	0.081	-9999	-0.34	18	18
RHOA	0.005	0.08	-9999	-0.52	12	12
S1P/S1P3/Gq	-0.028	0.095	-9999	-0.27	59	59
GNAQ	0	0	-9999	-10000	0	0
GNAZ	0.003	0.085	-9999	-0.43	18	18
G12/G13	0.02	0.043	-9999	-0.37	5	5
GNA14	-0.081	0.18	-9999	-0.35	141	141
GNA15	0.001	0.078	-9999	-0.33	25	25
GNA12	0.018	0	-9999	-10000	0	0
GNA13	0.009	0.059	-9999	-0.38	11	11
GNA11	0.014	0.047	-9999	-0.52	4	4
Rac1/GTP	0.018	0.075	-9999	-0.38	6	6

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.014	0.047	-10000	0	-0.52	4	4
RAS family/GTP/Tiam1	0.003	0.08	-10000	0	-0.28	28	28
NT3 (dimer)/TRKC	-0.018	0.093	-10000	0	-0.35	16	16
NT3 (dimer)/TRKB	-0.015	0.1	-10000	0	-0.32	36	36
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	0.092	-10000	0	-0.26	64	64
PIK3CA	0.016	0.029	-10000	0	-0.35	3	3
DYNLT1	0.018	0	-10000	0	-10000	0	0
NTRK1	0.01	0.054	-10000	0	-0.32	12	12
NTRK2	-0.017	0.11	-10000	0	-0.34	52	52
NTRK3	-0.009	0.082	-10000	0	-0.26	52	52
NT-4/5 (dimer)/TRKB	-0.004	0.079	-10000	0	-0.31	23	23
neuron apoptosis	0.036	0.15	0.34	80	-10000	0	80
SHC 2-3/Grb2	-0.04	0.16	-10000	0	-0.37	80	80
SHC1	0.017	0.023	-10000	0	-0.52	1	1
SHC2	-0.062	0.2	-10000	0	-0.5	79	79
SHC3	-0.007	0.11	-10000	0	-0.46	18	18
STAT3 (dimer)	-0.045	0.14	-10000	0	-0.34	89	89
NT3 (dimer)/TRKA	0.001	0.083	-10000	0	-0.34	16	16
RIN/GDP	0.048	0.049	-10000	0	-0.31	1	1
GIPC1	0.014	0.042	-10000	0	-0.46	4	4
KRAS	0.008	0.069	-10000	0	-0.45	11	11
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	-0.46	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	-0.26	4	4
NGF (dimer)/TRKA/MATK	0.008	0.055	-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	-0.26	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	0.047	-10000	0	-0.26	16	16
RIT2	0.015	0.035	-10000	0	-0.43	3	3
RIT1	0.016	0.033	-10000	0	-0.52	2	2
FRS2	0.01	0.047	-10000	0	-0.28	13	13
DNM1	0.012	0.052	-10000	0	-0.39	8	8
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	20	-0.25	6	26
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	32	32
BDNF (dimer)/TRKB	-0.008	0.091	-10000	0	-0.32	24	24
KIDINS220/CRKL/C3G	0.023	0.034	-10000	0	-0.37	4	4
SHC/RasGAP	0.016	0.06	-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	-0.27	11	11
RIT1/GTP	0.012	0.024	-10000	0	-0.38	2	2
NT3 (dimer)	-0.021	0.1	-10000	0	-0.28	67	67
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	0.092	-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	-0.28	1	1
RAP1B	0.013	0.044	-10000	0	-0.32	8	8
RAP1A	0.011	0.062	-10000	0	-0.52	7	7
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	0.024	-10000	0	-0.37	1	1
Rap1/GTP	0.029	0.074	-10000	0	-0.45	5	5
STAT3	-0.045	0.14	-10000	0	-0.34	89	89
axon guidance	-0.042	0.074	-10000	0	-0.34	14	14
MAPK3	0.013	0.051	-10000	0	-0.27	8	8
MAPK1	0.013	0.052	-10000	0	-0.27	9	9
CDC42/GDP	0.048	0.048	-10000	0	-0.31	1	1
NTF3	-0.021	0.1	-10000	0	-0.28	67	67
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.018	0.036	-10000	0	-0.31	4	4
PI3K	0.006	0.082	-10000	0	-0.37	21	21
FRS3	0.017	0.012	-10000	0	-0.26	1	1
FAIM	0.016	0.029	-10000	0	-0.35	3	3
GAB1	0.006	0.074	-10000	0	-0.43	14	14
RASGRF1	0.006	0.076	0.23	19	-0.27	11	30
SOS1	0.017	0.023	-10000	0	-0.52	1	1
MCF2L	-0.008	0.082	-10000	0	-0.3	20	20
RGS19	0.014	0.039	-10000	0	-0.36	5	5
CDC42	0.018	0	-10000	0	-10000	0	0
RAS family/GTP	0.046	0.072	-10000	0	-0.4	5	5
Rac1/GDP	0.048	0.048	-10000	0	-0.31	1	1
NGF (dimer)/TRKA/GRIT	0.011	0.06	-10000	0	-0.31	15	15
neuron projection morphogenesis	-0.013	0.13	-10000	0	-0.53	10	10
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	0.066	-10000	0	-0.29	23	23
NGF (dimer)/TRKA/GIPC/GAIP	0.027	0.053	-10000	0	-0.31	10	10
RAS family/GTP/PI3K	0.011	0.077	-10000	0	-0.25	39	39
FRS2 family/SHP2/GRB2/SOS1	0.047	0.038	-10000	0	-0.38	2	2
NRAS	0.006	0.072	-10000	0	-0.4	15	15
GRB2/SOS1	0.024	0.024	-10000	0	-0.37	1	1
PRKCI	0.001	0.088	-10000	0	-0.44	19	19
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	0.051	-10000	0	-0.47	4	4
RASA1	0.004	0.079	-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	0.006	0.082	-10000	0	-0.28	22	22
NGF (dimer)/TRKA/p62/Atypical PKCs	0.016	0.061	-10000	0	-0.26	21	21
MATK	-0.003	0.076	-10000	0	-0.27	38	38
NEDD4L	-0.025	0.14	-10000	0	-0.46	48	48
RAS family/GDP	-0.01	0.032	-10000	0	-0.28	1	1
NGF (dimer)/TRKA	0.009	0.071	0.24	21	-0.28	6	27
Rac1/GTP	-0.02	0.052	-10000	0	-0.23	17	17
FRS2 family/SHP2/CRK family	0.045	0.043	-10000	0	-0.26	8	8

×

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

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
MET/RANBP9	0.013	0.056	-10000	0	-0.37	5	5
CRKL	0.02	0.086	-10000	0	-0.44	12	12
mol:PIP3	-0.004	0.091	0.47	19	-10000	0	19
AKT1	0.007	0.068	0.34	18	-0.28	4	22
PTK2B	0.017	0.017	-10000	0	-0.26	2	2
RAPGEF1	0.026	0.082	-10000	0	-0.42	11	11
RANBP10	0.018	0	-10000	0	-10000	0	0
PIK3CA	0.016	0.029	-10000	0	-0.35	3	3
HGF/MET/SHIP2	0.015	0.072	-10000	0	-0.31	19	19
MAP3K5	0.018	0.1	-10000	0	-0.4	15	15
HGF/MET/CIN85/CBL/ENDOPHILINS	0.021	0.079	-10000	0	-0.29	24	24
AP1	-0.088	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	0.059	-10000	0	-0.29	2	2
GAB1/CRKL/SHP2/PI3K	0.029	0.098	-10000	0	-0.4	15	15
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.03	0.082	-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	0.037	0.25	3	-0.18	7	10
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.022	0.045	-10000	0	-0.23	7	7
PAK1	-0.005	0.089	0.32	17	-0.27	28	45
HGF/MET/RANBP10	0.019	0.065	-10000	0	-0.31	14	14
HRAS	0.024	0.081	-10000	0	-0.53	7	7
DOCK1	0.021	0.094	-10000	0	-0.47	11	11
GAB1	0.015	0.087	-10000	0	-0.42	15	15
CRK	0.021	0.085	-10000	0	-0.45	11	11
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0.087	-10000	0	-0.49	13	13
JUN	-0.034	0.15	-10000	0	-0.46	57	57
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.005	0.052	-10000	0	-0.24	18	18
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
cell morphogenesis	0.038	0.089	-10000	0	-0.36	9	9
GRB2/SHC	0.024	0.05	-10000	0	-0.23	12	12
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	0.037	0.25	3	-0.18	7	10
HGF/MET/MUC20	0.007	0.064	-10000	0	-0.32	14	14
cell migration	0.023	0.049	-10000	0	-0.23	12	12
GRB2	0.016	0.024	-10000	0	-0.26	4	4
CBL	0.017	0.012	-10000	0	-0.26	1	1
MET/RANBP10	0.013	0.055	-10000	0	-0.37	5	5
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.025	0.06	-10000	0	-0.23	24	24
MET/MUC20	0	0.054	-10000	0	-0.2	31	31
RAP1B	0.03	0.081	-10000	0	-0.39	12	12
RAP1A	0.029	0.088	-10000	0	-0.44	12	12
HGF/MET/RANBP9	0.019	0.065	-10000	0	-0.31	14	14
RAF1	0.03	0.077	-10000	0	-0.49	7	7
STAT3	0.029	0.06	-10000	0	-0.29	2	2
cell proliferation	0.036	0.072	-10000	0	-0.32	14	14
RPS6KB1	0.009	0.024	-10000	0	-0.15	1	1
MAPK3	-0.011	0.041	0.66	1	-10000	0	1
MAPK1	-0.009	0.055	0.76	2	-10000	0	2
RANBP9	0.017	0.012	-10000	0	-0.26	1	1
MAPK8	0.025	0.093	-10000	0	-0.38	10	10
SRC	0.029	0.059	-10000	0	-0.26	4	4
PI3K	0.011	0.078	-10000	0	-0.26	30	30
MET/Glomulin	0.004	0.049	-10000	0	-0.18	32	32
SOS1	0.017	0.023	-10000	0	-0.52	1	1
MAP2K1	0.036	0.073	-10000	0	-0.48	6	6
MET	-0.001	0.078	-10000	0	-0.3	31	31
MAP4K1	0.029	0.082	-10000	0	-0.44	10	10
PTK2	0.016	0.029	-10000	0	-0.35	3	3
MAP2K2	0.035	0.076	-10000	0	-0.5	6	6
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	0.068	-10000	0	-0.38	13	13
INPPL1	0.012	0.055	-10000	0	-0.45	7	7
PXN	0.018	0	-10000	0	-10000	0	0
SH3KBP1	0.001	0.083	-10000	0	-0.38	22	22
HGS	0.012	0.049	-10000	0	-0.22	19	19
PLCgamma1/PKC	0.012	0.019	-10000	0	-0.28	2	2
HGF	0.008	0.069	-10000	0	-0.45	11	11
RASA1	0.004	0.079	-10000	0	-0.42	16	16
NCK1	0.011	0.046	-10000	0	-0.28	12	12
PTPRJ	0.012	0.055	-10000	0	-0.45	7	7
NCK/PLCgamma1	0.024	0.056	-10000	0	-0.24	13	13
PDPK1	0.003	0.071	0.38	18	-10000	0	18
HGF/MET/SHIP	0.007	0.064	-10000	0	-0.32	14	14

×

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	0.078	-9999	-0.38	17	17
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	-0.024	0.099	-9999	-0.26	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	0.007	0.083	-9999	-0.41	16	16
EPO/EPOR (dimer)	-0.003	0.069	-9999	-0.32	1	1
lamellipodium assembly	0.022	0.069	-9999	-0.35	6	6
PIK3CA	0.016	0.029	-9999	-0.35	3	3
PI3K	0.006	0.082	-9999	-0.37	21	21
ARF6	0.016	0.033	-9999	-0.52	2	2
JAK2	0.007	0.076	-9999	-0.31	18	18
PXN	0.018	0	-9999	-10000	0	0
PIK3R1	-0.009	0.11	-9999	-0.42	32	32
MADCAM1	0.014	0.034	-9999	-0.26	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	0.015	0.037	-9999	-0.39	4	4
SRC	0	0.1	-9999	-0.3	47	47
ITGB7	0.018	0	-9999	-10000	0	0
RAC1	0.018	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.004	0.11	-9999	-0.34	45	45
p130Cas/Crk/Dock1	0.019	0.099	-9999	-0.45	7	7
VCAM1	-0.021	0.13	-9999	-0.42	47	47
RHOA	0.005	0.08	-9999	-0.52	12	12
alpha4/beta1 Integrin/Paxillin/GIT1	0.028	0.069	-9999	-0.3	17	17
BCAR1	0.007	0.097	-9999	-0.29	41	41
EPOR	0.017	0.017	-9999	-0.26	2	2
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.017	0.012	-9999	-0.26	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	-0.35	3	3
Calcineurin A alpha-beta B1/CABIN1	0.004	0.092	-10000	0	-0.36	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	0.023	0.085	-10000	0	-0.39	8	8
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	0.021	-10000	0	-0.26	3	3
MAPK14	0.018	0.012	-10000	0	-0.26	1	1
BAD	0.017	0.023	-10000	0	-0.52	1	1
CABIN1/MEF2D	0.013	0.088	-10000	0	-0.38	10	10
Calcineurin A alpha-beta B1/BCL2	-0.12	0.22	-10000	0	-0.47	145	145
FKBP8	0.017	0.012	-10000	0	-0.26	1	1
activation-induced cell death of T cells	-0.013	0.087	0.37	10	-10000	0	10
KPNB1	0.013	0.052	-10000	0	-0.52	5	5
KPNA2	-0.002	0.088	-10000	0	-0.35	28	28
XPO1	0.018	0	-10000	0	-10000	0	0
SFN	-0.015	0.12	-10000	0	-0.45	37	37
MAP3K8	-0.035	0.15	-10000	0	-0.39	69	69
NFAT4/CK1 alpha	0.01	0.075	-10000	0	-0.24	38	38
MEF2D/NFAT1/Cbp/p300	0.057	0.059	-10000	0	-0.38	2	2
CABIN1	0.004	0.092	-10000	0	-0.37	13	13
CALM1	0.018	0.001	-10000	0	-10000	0	0
RAN	0.017	0.012	-10000	0	-0.26	1	1
MAP3K1	-0.031	0.14	-10000	0	-0.43	58	58
CAMK4	0.011	0.047	-10000	0	-0.31	10	10
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	-0.011	0.11	-10000	0	-0.37	40	40
YWHAB	0.015	0.037	-10000	0	-0.39	4	4
MAPK8	0.015	0.04	-10000	0	-0.52	3	3
MAPK9	-0.006	0.11	-10000	0	-0.51	24	24
YWHAG	0.017	0.017	-10000	0	-0.26	2	2
FKBP1A	0.017	0.017	-10000	0	-0.26	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	0.036	-10000	0	-0.26	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	0.011	0.056	-10000	0	-0.42	8	8
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	-0.46	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	0.034	-10000	0	-0.26	8	8
PRKCG	0.018	0	-10000	0	-10000	0	0
PRKCQ	-0.014	0.1	-10000	0	-0.32	51	51
FKBP38/BCL2	-0.071	0.16	-10000	0	-0.37	115	115
EP300	0.014	0.047	-10000	0	-0.52	4	4
PRKCB1	-0.051	0.16	-10000	0	-0.39	88	88
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	0.022	0.028	-10000	0	-0.31	2	2
NFATc/ERK1	0.041	0.073	-10000	0	-0.49	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.02	0.087	-10000	0	-0.38	10	10
NR4A1	0.052	0.066	-10000	0	-0.52	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	-0.035	0.15	-10000	0	-0.42	63	63
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	-0.26	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	-0.12	0.22	-10000	0	-0.47	145	145

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.003	0.14	-9999	-1	5	5
MKNK1	0.018	0	-9999	-10000	0	0
MAPK14	0.005	0.055	-9999	-0.29	6	6
ATF2/c-Jun	-0.028	0.19	-9999	-0.64	44	44
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	-0.005	0.1	-9999	-0.34	32	32
MAPKAPK3	0.017	0.017	-9999	-0.26	2	2
MAPKAPK2	0.014	0.047	-9999	-0.52	4	4
p38alpha-beta/CK2	0.008	0.074	-9999	-0.39	6	6
CEBPB	0.011	0.073	-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	0.08	-9999	-0.31	6	6
p38alpha-beta/MNK1	0.022	0.059	-9999	-0.32	5	5
JUN	-0.028	0.19	-9999	-0.63	44	44
PPARGC1A	0.002	0.089	-9999	-0.35	15	15
USF1	0.005	0.085	-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	0.067	-9999	-0.37	6	6
RAB5A	0.018	0	-9999	-10000	0	0
HSPB1	-0.013	0.12	-9999	-0.33	54	54
p38alpha-beta/HBP1	0.02	0.066	-9999	-0.34	8	8
CREB1	0.013	0.076	-9999	-0.34	6	6
RAB5/GDP	0.013	0	-9999	-10000	0	0
EIF4E	0.024	0.049	-9999	-0.27	5	5
RPS6KA4	0.017	0.061	-9999	-0.32	6	6
PLA2G4A	-0.007	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	-0.35	33	33
ESR1	-0.091	0.17	-9999	-0.34	154	154
HBP1	0.015	0.04	-9999	-0.52	3	3
MEF2C	-0.001	0.1	-9999	-0.34	31	31
MEF2A	0.017	0.062	-9999	-0.33	6	6
EIF4EBP1	0.008	0.081	-9999	-0.34	8	8
KRT19	-0.014	0.12	-9999	-0.34	53	53
ELK4	0.015	0.066	-9999	-0.31	9	9
ATF6	0.017	0.061	-9999	-0.32	6	6
ATF1	0.013	0.077	-9999	-0.34	6	6
p38alpha-beta/MAPKAPK2	0.02	0.07	-9999	-0.37	8	8
p38alpha-beta/MAPKAPK3	0.022	0.06	-9999	-0.32	5	5

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.03	0.17	-10000	0	-0.46	10	10
CRKL	0.006	0.075	-10000	0	-0.3	8	8
mol:DAG	0.006	0.083	-10000	0	-0.28	3	3
HRAS	0.023	0.075	-10000	0	-0.41	2	2
MAPK8	0.009	0.059	-10000	0	-0.28	4	4
RAP1A	0.004	0.079	-10000	0	-0.33	10	10
GAB1	0.002	0.081	-10000	0	-0.28	13	13
MAPK14	0.011	0.054	-10000	0	-0.25	1	1
EPO	-0.025	0.099	-10000	0	-0.26	80	80
PLCG1	0.005	0.084	-10000	0	-0.29	3	3
EPOR/TRPC2/IP3 Receptors	0.014	0.02	-10000	0	-0.27	2	2
RAPGEF1	0.018	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0	0.073	-10000	0	-0.33	9	9
GAB1/SHC/GRB2/SOS1	0.019	0.074	-10000	0	-0.43	2	2
EPO/EPOR (dimer)	-0.005	0.071	-10000	0	-0.19	30	30
IRS2	-0.014	0.1	-10000	0	-0.3	34	34
STAT1	-0.027	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	0.067	-10000	0	-0.31	12	12
TEC	0.005	0.075	-10000	0	-0.27	10	10
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	0.055	-10000	0	-0.33	12	12
PIK3R1	-0.009	0.11	-10000	0	-0.42	32	32
EPO/EPOR (dimer)/JAK2	0.015	0.083	-10000	0	-0.29	6	6
EPO/EPOR	-0.005	0.071	-10000	0	-0.19	30	30
LYN	0.012	0.033	-10000	0	-0.27	7	7
TEC/VAV2	0.014	0.076	-10000	0	-0.3	6	6
elevation of cytosolic calcium ion concentration	0.014	0.02	-10000	0	-0.27	2	2
SHC1	0.017	0.023	-10000	0	-0.52	1	1
EPO/EPOR (dimer)/LYN	0.009	0.066	-10000	0	-0.29	1	1
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	38	38
SH2B3	0.015	0.024	-10000	0	-0.52	1	1
NFKB1	0.01	0.056	-10000	0	-0.28	2	2
EPO/EPOR (dimer)/JAK2/SOCS3	-0.005	0.051	0.26	1	-0.22	13	14
PTPN6	0	0.073	-10000	0	-0.29	6	6
TEC/VAV2/GRB2	0.021	0.075	-10000	0	-0.29	5	5
EPOR	0.014	0.02	-10000	0	-0.27	2	2
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	-0.29	5	5
CBL	0.007	0.07	-10000	0	-0.31	4	4
SHC/Grb2/SOS1	-0.021	0.044	-10000	0	-0.33	2	2
STAT5A	-0.005	0.11	-10000	0	-0.36	5	5
GRB2	0.016	0.024	-10000	0	-0.26	4	4
STAT5 (dimer)	-0.013	0.15	-10000	0	-0.36	36	36
LYN/PLCgamma2	-0.002	0.081	-10000	0	-0.36	15	15
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	115	115

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.012	0.051	-9999	-0.31	12	12
ADCY5	-0.01	0.074	-9999	-0.32	14	14
ADCY6	0.015	0.04	-9999	-0.31	7	7
ADCY7	0.008	0.058	-9999	-0.32	13	13
ADCY1	0.015	0.036	-9999	-0.31	5	5
ADCY2	-0.029	0.11	-9999	-0.32	50	50
ADCY3	0.011	0.052	-9999	-0.31	12	12
ADCY8	0.012	0.044	-9999	-0.31	6	6
PRKCE	0.008	0.04	-9999	-0.3	8	8
ADCY9	0.002	0.075	-9999	-0.32	24	24
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.001	0.069	-9999	-0.29	13	13

×

a4b1 and a4b7 Integrin signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.015	0.037	-9999	-0.39	4	4
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	0.007	0.083	-9999	-0.41	16	16

×

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	0.046	-10000	0	-0.28	12	12
Glucocorticoid receptor/Hsp90/HDAC6	0.02	0.071	-10000	0	-0.3	23	23
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	0.014	-10000	0	-0.2	1	1
GATA2	-0.008	0.094	-10000	0	-0.32	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	0.047	-10000	0	-0.31	10	10
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	-0.35	3	3
NR3C1	-0.003	0.1	-10000	0	-0.51	21	21
SUMO1/HDAC4	0.036	0.02	-10000	0	-0.31	1	1
SRF	0.016	0.024	-10000	0	-0.26	4	4
HDAC4/YWHAB	0.023	0.032	-10000	0	-0.37	3	3
Tubulin	0.01	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	-0.3	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	0.031	0.035	-10000	0	-0.3	3	3
HDAC4/ER alpha	-0.1	0.18	-10000	0	-0.37	150	150
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	-0.46	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	-0.45	202	202
HDAC6/HDAC11	0.004	0.089	-10000	0	-0.37	28	28
Ran/GTP/Exportin 1	0.039	0.014	-10000	0	-10000	0	0
NPC	0.01	0.008	-10000	0	-10000	0	0
MEF2C	-0.013	0.12	-10000	0	-0.45	35	35
RAN	0.017	0.012	-10000	0	-0.26	1	1
HDAC4/MEF2C	0.035	0.067	-10000	0	-0.24	27	27
GNG2	0.016	0.029	-10000	0	-0.35	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	-0.26	2	2
ANKRA2	0	0.095	-10000	0	-0.52	17	17
RFXANK	0.017	0.012	-10000	0	-0.26	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	0.072	-10000	0	-0.34	16	16
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	-0.35	3	3
PI3K	0.006	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	32	32
ARF6/GTP	0.031	0.06	-10000	0	-0.47	2	2
cell adhesion	0.034	0.063	-10000	0	-0.27	17	17
CRKL/CBL	0.023	0.035	-10000	0	-0.37	4	4
alpha4/beta1 Integrin/Paxillin	0.026	0.066	-10000	0	-0.3	16	16
ITGB1	0.015	0.037	-10000	0	-0.39	4	4
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	0.016	0.1	-10000	0	-0.29	39	39
p130Cas/Crk/Dock1	0.027	0.054	-10000	0	-0.3	13	13
VCAM1	-0.021	0.13	-10000	0	-0.42	47	47
alpha4/beta1 Integrin/Paxillin/Talin	0.036	0.064	-10000	0	-0.28	17	17
alpha4/beta1 Integrin/Paxillin/GIT1	0.034	0.065	-10000	0	-0.28	17	17
BCAR1	0.017	0.012	-10000	0	-0.26	1	1
mol:GDP	-0.033	0.064	0.27	17	-10000	0	17
CBL	0.017	0.012	-10000	0	-0.26	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	0.036	0.064	-10000	0	-0.28	17	17
Rac1/GTP	-0.019	0.087	-10000	0	-0.38	22	22

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.001	0.084	-9999	-0.37	23	23
Aurora C/Aurora B/INCENP	0.015	0.063	-9999	-0.28	15	15
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	0.054	-9999	-0.27	18	18

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	-0.01	0.068	0.39	10	-10000	0	10
KIRREL	0.009	0.071	-10000	0	-0.53	9	9
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.01	0.068	-10000	0	-0.39	10	10
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	0.029	0.058	-10000	0	-0.28	13	13
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.025	0.06	-10000	0	-0.25	13	13
FYN	0.015	0.057	-10000	0	-0.25	18	18
mol:Ca2+	0.028	0.059	-10000	0	-0.3	12	12
mol:DAG	0.028	0.059	-10000	0	-0.3	12	12
NPHS2	0.015	0.036	-10000	0	-0.43	3	3
mol:IP3	0.028	0.059	-10000	0	-0.3	12	12
regulation of endocytosis	0.028	0.056	-10000	0	-0.26	12	12
Nephrin/NEPH1/podocin/Cholesterol	0.019	0.054	-10000	0	-0.28	12	12
establishment of cell polarity	0.01	0.068	-10000	0	-0.39	10	10
Nephrin/NEPH1/podocin/NCK1-2	0.035	0.059	-10000	0	-0.25	13	13
Nephrin/NEPH1/beta Arrestin2	0.03	0.057	-10000	0	-0.26	12	12
NPHS1	0.004	0.062	-10000	0	-0.27	25	25
Nephrin/NEPH1/podocin	0.021	0.059	-10000	0	-0.25	18	18
TJP1	0.013	0.052	-10000	0	-0.52	5	5
NCK1	0.011	0.046	-10000	0	-0.28	12	12
NCK2	0.015	0.027	-10000	0	-0.26	5	5
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.029	0.06	-10000	0	-0.3	12	12
CD2AP	0.016	0.029	-10000	0	-0.35	3	3
Nephrin/NEPH1/podocin/GRB2	0.029	0.056	-10000	0	-0.27	12	12
GRB2	0.016	0.024	-10000	0	-0.26	4	4
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	0.012	0.067	-10000	0	-0.27	23	23
cytoskeleton organization	0.03	0.062	-10000	0	-0.28	13	13
Nephrin/NEPH1	0.011	0.048	-10000	0	-0.28	10	10
Nephrin/NEPH1/ZO-1	0.019	0.064	-10000	0	-0.31	15	15

×

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	-0.26	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	-0.003	0.093	-10000	0	-0.32	37	37
CRY2	0.017	0.012	-10000	0	-0.26	1	1
mol:CO	-0.014	0.012	0.14	1	-10000	0	1
CHEK1	-0.045	0.15	-10000	0	-0.38	83	83
mol:HEME	0.014	0.012	-10000	0	-0.14	1	1
PER1	0.014	0.037	-10000	0	-0.3	7	7
BMAL/CLOCK/NPAS2	0.03	0.082	-10000	0	-0.32	21	21
BMAL1/CLOCK	0.042	0.077	-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	0.018	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	0.08	0.3	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	-0.26	4	4
RhoA/GTP	0.01	0.082	-10000	0	-0.31	16	16
negative regulation of cAMP metabolic process	0.008	0.075	-10000	0	-0.31	12	12
GNAZ	0.002	0.085	-10000	0	-0.43	18	18
GNAI3	0.017	0.023	-10000	0	-0.52	1	1
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	0.075	-10000	0	-0.32	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	-0.015	0.12	-10000	0	-0.38	44	44

×

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	0.081	-9999	-1.3	1	1
PLK1	0.029	0.18	-9999	-0.68	9	9
CDKN1B	0.062	0.18	-9999	-0.48	31	31
FOXO3	0.021	0.19	-9999	-0.58	20	20
KAT2B	0.003	0.021	-9999	-0.051	16	16
FOXO1/SIRT1	0.036	0.066	-9999	-0.37	5	5
CAT	0.023	0.2	-9999	-0.92	10	10
CTNNB1	0.001	0.09	-9999	-0.45	19	19
AKT1	0.019	0.057	-9999	-0.36	9	9
FOXO1	0.036	0.067	-9999	-0.39	4	4
MAPK10	0.014	0.074	-9999	-0.25	28	28
mol:GTP	0.001	0.003	-9999	-10000	0	0
FOXO4	0.06	0.1	-9999	-0.4	5	5
response to oxidative stress	0.008	0.022	-9999	-0.05	21	21
FOXO3A/SIRT1	0.034	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	-0.05	21	21
RAN	0.018	0.012	-9999	-0.26	1	1
GADD45A	0.037	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	0.031	-9999	-0.3	3	3
CSNK1D	0.018	0	-9999	-10000	0	0
CSNK1E	0.017	0.012	-9999	-0.26	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	-0.26	2	2
YWHAE	0.016	0.029	-9999	-0.35	3	3
YWHAZ	0.017	0.017	-9999	-0.26	2	2
SIRT1	0.018	0.035	-9999	-0.35	3	3
SOD2	0.065	0.17	-9999	-0.67	8	8
RBL2	0.045	0.16	-9999	-0.77	7	7
RAL/GDP	0.031	0.034	-9999	-0.31	4	4
CHUK	0.008	0.083	-9999	-0.5	13	13
Ran/GTP	0.016	0.009	-9999	-0.17	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	-0.26	1	1
FASLG	-0.12	0.41	-9999	-1.4	49	49
SKP2	0.007	0.053	-9999	-0.26	20	20
USP7	0.018	0.013	-9999	-0.27	1	1
IKBKB	0.015	0.051	-9999	-0.31	10	10
CCNB1	-0.021	0.32	-9999	-1.1	38	38
FOXO1-3a-4/beta catenin	0.067	0.17	-9999	-0.41	22	22
proteasomal ubiquitin-dependent protein catabolic process	0.035	0.07	-9999	-0.42	5	5
CSNK1A1	0.017	0.023	-9999	-0.52	1	1
SGK1	0.003	0.021	-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	0.066	0.09	-9999	-0.39	1	1
SFN	-0.015	0.12	-9999	-0.45	37	37
CDK2	0.015	0.047	-9999	-0.31	10	10
FOXO3A/14-3-3	0.043	0.08	-9999	-0.38	5	5
CREBBP	0.019	0.033	-9999	-0.52	2	2
FBXO32	-0.01	0.3	-9999	-1.2	25	25
BCL6	0.015	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	0.079	-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	0.032	0.071	-10000	0	-0.34	10	10
SMAD4/Ubc9/PIASy	0.027	0.052	-10000	0	-0.3	12	12
SMAD2/SMAD2/SMAD4	0.03	0.062	-10000	0	-10000	0	0
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	-0.27	8	9
MAP3K1	-0.031	0.14	-10000	0	-0.43	58	58
TRAP-1/SMAD4	0.02	0.05	-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	-0.42	5	5
CTDSPL	0.011	0.062	-10000	0	-0.52	7	7
KPNB1	0.013	0.052	-10000	0	-0.52	5	5
TGFBRAP1	0.017	0.012	-10000	0	-0.26	1	1
UBE2I	0.018	0	-10000	0	-10000	0	0
NUP153	0.016	0.024	-10000	0	-0.26	4	4
KPNA2	-0.002	0.088	-10000	0	-0.35	28	28
PIAS4	0.013	0.05	-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	-0.32	7	7
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	0.021	-9999	-0.26	3	3
IKBKB	0.011	0.047	-9999	-0.31	10	10
RIPK2	0.013	0.041	-9999	-0.29	9	9
IKBKG	0.016	0.091	-9999	-0.51	5	5
IKK complex/A20	0.026	0.1	-9999	-0.44	9	9
NEMO/A20/RIP2	0.012	0.041	-9999	-0.29	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	-0.26	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	-0.47	81	81
NFKB1	0.019	0.025	-9999	-0.52	1	1
RELA	0.02	0.009	-9999	-10000	0	0
MALT1	0.011	0.054	-9999	-0.38	9	9
cIAP1/UbcH5C	0.025	0.014	-9999	-10000	0	0
ATM	0.017	0.012	-9999	-0.26	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	0.034	-9999	-0.26	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	-0.26	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	-0.43	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	-0.42	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	0.069	-9999	-0.35	17	17
FYN	0.016	0.054	-9999	-0.28	14	14
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	0.026	0.071	-10000	0	-0.44	6	6
FRAP1	0.018	0	-10000	0	-10000	0	0
PRKDC	0.012	0.046	-10000	0	-0.32	9	9
FOXO3	0.033	0.062	-10000	0	-0.46	6	6
AKT1	0.03	0.054	-10000	0	-0.43	6	6
BAD	0.017	0.023	-10000	0	-0.52	1	1
AKT3	0.008	0.044	-10000	0	-0.32	4	4
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	-0.26	1	1
JNK cascade	-0.017	0.078	0.35	10	-10000	0	10
TSC1	0.036	0.051	-10000	0	-0.4	6	6
YWHAZ	0.017	0.017	-10000	0	-0.26	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	0.064	-10000	0	-0.3	19	19
MAP3K5	-0.021	0.13	-10000	0	-0.42	46	46
MAPKAP1	0.016	0.026	-10000	0	-0.39	2	2
negative regulation of cell cycle	-0.034	0.049	0.26	2	-10000	0	2
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	-0.35	3	3
SRC	0.015	0.035	-10000	0	-0.43	3	3
AKT2/p21CIP1	0.03	0.067	-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	0.053	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	-0.3	3	3
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	0.028	0.067	-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	-0.26	2	2
RHEB	0.016	0.026	-10000	0	-0.39	2	2
CREBBP	0.016	0.033	-10000	0	-0.52	2	2

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.016	0.024	-9999	-0.26	4	4
CDC42/GTP	0.017	0.069	-9999	-0.39	5	5
PLCG1	0.014	0.072	-9999	-0.38	6	6
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.006	0.075	-9999	-0.48	12	12
GNAI3	0.017	0.023	-9999	-0.52	1	1
G12/G13	0.02	0.043	-9999	-0.37	5	5
cell migration	0.016	0.068	-9999	-0.38	5	5
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
MAPK3	0.014	0.072	-9999	-0.38	6	6
MAPK1	0.014	0.073	-9999	-0.36	7	7
S1P/S1P5/Gi	0.008	0.075	-9999	-0.32	12	12
GNAI1	-0.015	0.12	-9999	-0.38	44	44
CDC42/GDP	0.013	0	-9999	-10000	0	0
S1P/S1P5/G12	0.012	0	-9999	-10000	0	0
RHOA	0.016	0.057	-9999	-0.3	15	15
S1P/S1P4/Gi	0.008	0.075	-9999	-0.32	12	12
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.002	0.085	-9999	-0.43	18	18
S1P/S1P4/G12/G13	0.018	0.033	-9999	-0.28	5	5
GNA12	0.018	0	-9999	-10000	0	0
GNA13	0.009	0.059	-9999	-0.38	11	11
CDC42	0.018	0	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.038	0.061	-9999	-0.39	3	3
CaM/Ca2+	0.013	0	-9999	-10000	0	0
AKT1	0.011	0.054	-9999	-0.38	9	9
AKT2	0.017	0.012	-9999	-0.26	1	1
STXBP4	0.008	0.061	-9999	-0.33	15	15
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	0.033	0.054	-9999	-0.29	2	2
YWHAZ	0.017	0.017	-9999	-0.26	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	-0.26	2	2
ASIP	0	0	-9999	-10000	0	0
PRKCI	0.001	0.088	-9999	-0.44	19	19
AS160/CaM/Ca2+	0.013	0	-9999	-10000	0	0
RHOQ	0.014	0.042	-9999	-0.46	4	4
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	0.019	0.04	-9999	-0.31	7	7
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	0.057	-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	0.061	-9999	-0.43	9	9
YWHAE	0.016	0.029	-9999	-0.35	3	3

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.014	-10000	0	-0.2	1	1
FKBP3	0.013	0.048	-10000	0	-0.47	5	5
Histones	0.043	0.051	-10000	0	-0.28	2	2
YY1/LSF	0.021	0.055	-10000	0	-0.26	19	19
SMG5	0.016	0.029	-10000	0	-0.35	3	3
RAN	0.017	0.012	-10000	0	-0.26	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	-0.3	7	7
HDAC3/TR2	0.026	0.053	-10000	0	-0.28	9	9
NuRD/MBD3 Complex	0.045	0.038	-10000	0	-0.27	2	2
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	-0.008	0.094	-10000	0	-0.32	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	0.033	0.045	-10000	0	-0.29	2	2
YY1/HDAC2	0.023	0.044	-10000	0	-0.25	10	10
YY1/HDAC1	0.027	0.034	-10000	0	-0.23	9	9
NuRD/MBD2 Complex (MeCP1)	0.044	0.038	-10000	0	-0.27	2	2
PPARG	0.007	0.095	-10000	0	-0.3	37	37
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	-0.46	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	0.052	-10000	0	-0.33	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	0.054	-10000	0	-0.29	15	15
YY1	0.021	0.036	-10000	0	-0.27	8	8
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	-0.26	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	-0.26	2	2
YY1/LSF/HDAC1	0.03	0.053	-10000	0	-0.26	12	12
YY1/SAP30/HDAC1	0.033	0.046	-10000	0	-0.3	6	6
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	-0.27	2	2
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	-0.3	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	-10000	0	0
NuRD Complex	0.052	0.044	-10000	0	-0.33	2	2
positive regulation of chromatin silencing	0.04	0.049	-10000	0	-0.27	2	2
SIN3B	0.017	0.012	-10000	0	-0.26	1	1
MTA2	0.014	0.044	-10000	0	-0.42	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	0.046	-10000	0	-0.26	7	7
GATA1/Fog1	0.02	0.05	-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	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.044	0.038	-10000	0	-0.27	2	2
Ran/GTP/Exportin 1	0.039	0.014	-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	-0.26	2	2

×

Arf6 trafficking events

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
SLC2A4	0.005	0.061	-10000	0	-0.27	24	24
CLTC	0.024	0.05	-10000	0	-0.49	3	3
calcium ion-dependent exocytosis	0.022	0.039	-10000	0	-0.28	4	4
Dynamin 2/GTP	0.025	0.028	-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	0.04	-10000	0	-0.39	2	2
CTNND1	0.029	0.029	-10000	0	-0.25	3	3
DNM2	0.017	0.012	-10000	0	-0.26	1	1
mol:PI-4-5-P2	0.028	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	0.041	-10000	0	-0.35	6	6
mol:Choline	0.021	0.04	-10000	0	-0.39	2	2
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	0.028	-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	0.086	-10000	0	-0.31	35	35
substrate adhesion-dependent cell spreading	0.022	0.078	-10000	0	-0.44	2	2
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	0.034	-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	0.022	0.079	-10000	0	-0.45	2	2
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	0.024	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	-0.013	0.12	-10000	0	-0.5	31	31
PLD1	0.016	0.049	-10000	0	-0.3	10	10
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	0.005	0.071	-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	0.08	-10000	0	-0.64	2	2
mol:Phosphatidic acid	0.021	0.04	-10000	0	-0.39	2	2
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	-0.26	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	-0.019	0.06	-10000	0	-0.58	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	-0.32	24	24
adrenocorticotropin secretion	0.005	0.042	-10000	0	-0.21	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	0.01	0.052	-10000	0	-0.33	11	11
GNG2	0.016	0.029	-10000	0	-0.35	3	3
CRH	0.007	0.061	-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	0.022	0.018	-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	0.041	-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	0.014	-10000	0	-0.17	3	3
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	0.015	-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	0.008	0.013	-10000	0	-0.12	3	3
AP2M1	0.013	0.05	-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	0.021	-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	-0.26	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	-0.3	5	5
PLD2	0.011	0.026	0.15	8	-0.19	4	12
ARF-GAP1/v-SNARE	0.012	0.014	-10000	0	-0.17	3	3
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	0.014	-10000	0	-0.17	3	3
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	0.013	-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	0.016	-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	-0.26	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.017	0.017	-9999	-0.26	2	2
SUMO1/HDAC4	0.036	0.02	-9999	-0.31	1	1
SUMO1/HDAC1	0.036	0.018	-9999	-0.24	1	1
RANGAP1	0.014	0.037	-9999	-0.3	7	7
MDM2/SUMO1/SUMO1	0.04	0.032	-9999	-0.27	2	2
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.023	0.014	-9999	-0.2	1	1
Ran/GTP	0.031	0.014	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.01	0.044	-9999	-0.26	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	-0.26	1	1
EntrezGene:9972	0	0	-9999	-10000	0	0